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Confidence Building Measure Return covering 2012

Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on their Destruction

Submitted to the United Nations on April 15, 2013

Declaration form on Nothing to Declare or Nothing New to Declare for use in the information exchange

Year of last Nothing declaration if Measure Nothing to declare new to nothing new to declare declare

A, part 1

A, part 2 (i)

A, part 2 (ii)

A, part 2 (iii)

F 1997 

Date: April 15, 2013

State Party to the Convention: United States of America

Date of ratification/accession to the Convention: March 26, 1975

National point of contact: Mr. Christopher Park, Department of State

Page 2 of 237

April 15, 2013

Report of the United States of America to the United Nations Department for Disarmament Affairs

Pursuant to the procedural modalities agreed upon in April 1987 at the "Ad Hoc Meeting of Scientific and Technical Experts for STATES Parties to the Convention on the Prohibition of the Development, Production, and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on Their Destruction," the United States of America submits the following information under Article V of the Convention: Confidence Building Measure A, Part 1 Exchange of data on research centres and laboratories page 4 Confidence Building Measure A, Part 2 Exchanges of information on national biological defence research and development programmes (i) Declaration page 15 (ii) Description page 17 (iii) Facilities page 38

Confidence Building Measure B Exchange of information on outbreaks of infectious diseases and similar page 188 occurrences caused by toxins Confidence Building Measure C Encouragement of publication of results and promotion of use of knowledge page 203

Confidence Building Measure E Declaration of legislature, regulations, and other measures page 208 Confidence Building Measure F Declaration of past activities in offensive and/or defensive biological research and page 213 development programmes Confidence Building Measure G Declaration of vaccine production facilities page 215 Appendix A List of the Biological Select Agents and Toxins, and NIAID Category A, B and C page 227 Priority Pathogens Appendix B Compiled list of biological agents and toxins used for biodefense research page 231

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Form A, Part 1 (i)

BWC - Confidence Building Measure

Exchange of data on research centres and laboratories

United States of America

April 15, 2013

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Form A, Part 1 (i) Exchange of data on research centres and laboratories1

1. Name(s) of facility2

National Biodefense Analysis and Countermeasures Center (NBACC) [Declared in accordance with Form A, Part 2 (iii)]

2. Responsible public or private organization or company.

U.S. Department of Homeland Security Science & Technology Directorate

operated by Battelle National Biodefense Institute LLC

3. Location and postal address.

8300 Research Plaza Fort Detrick, Maryland 21702

United States

4. Source(s) of financing of the reported activity, including indication if the activity is wholly or partly financed by the Ministry of Defence.

U.S. Department of Homeland Security (DHS) U.S. Department of Defense (DOD) - partly

U.S. Department of Justice (DOJ)

5. Number of maximum containment units3 within the research centre and/or laboratory, with an indication of their respective size (m2).

BSL 4 Laboratory 980 m2

6. Scope and general description of activities, including type(s) of microorganisms and/or toxins as appropriate.

NBACC conducts studies to better understand current and future biological threats; to assess vulnerabilities; and to determine potential impacts to guide the development of biological

countermeasures such as detectors, drugs, vaccines, and decontamination technologies.

1 The containment units which are fixed patient treatment modules, integrated with laboratories, should be identified separately. 2 For facilities with maximum containment units participating in the national biological defence research and development programme, please fill in name of facility and mark "Declared in accordance with Form A, part 2 (iii)". 3 In accordance with the latest edition of the WHO Laboratory Biosafety Manual, or equivalent. Page 5 of 237

When needed, NBACC conducts experimental programs to better characterize the benefits and risks of changes in U.S. biodefense preparations. NBACC also develops bioforensic assays and provides operational bioforensic analysis to support the attribution of biocrime and bioterrorism.

The types of agents registered for use at NBACC are BSL-2 toxins, BSL-2 gram positive and gram negative bacterial agents, BSL-2 viral agents, BSL-3 gram positive and gram negative bacterial agents, BSL-3 viral agents, and BSL-4 viral agents.

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Form A, Part 1 (i)

Exchange of data on research centres and laboratories1

1. Name(s) of facility2.

U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) [Declared in accordance with Form A, Part 2 (iii)]

2. Responsible public or private organization or company.

U.S. Army Medical Research and Materiel Command

3. Location and postal address.

1425 Porter Street Fort Detrick Frederick, Maryland 21702-5011 United States

4. Source(s) of financing of the reported activity, including indication if the activity is wholly or partly financed by the Ministry of Defence.

U.S. Department of Defense (DOD) - wholly

5. Number of maximum containment units3 within the research centre and/or laboratory, with an indication of their respective size (m2).

BSL 4 Laboratory 1186 m2

6. Scope and general description of activities, including type(s) of microorganisms and/or toxins as appropriate.

USAMRIID conducts research to develop strategies, products, information, procedures and training programs for medical defense against biological warfare threats and infectious diseases. Medical products developed to protect military personnel against biological agents include vaccines, drugs, diagnostic capabilities and various medical management

procedures.

Additional information can be found at: http://www.usamriid.army.mil/

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Form A, Part 1 (i)

Exchange of data on research centres and laboratories1

1. Name(s) of facility2.

CDC, Office of Infectious Diseases (OID) [Declared in accordance with Form A, Part 2 (iii)]

2. Responsible public or private organization or company.

Centers for Disease Control and Prevention, Department of Health and Human Services

3. Location and postal address.

1600 Clifton Road N.E. Atlanta, Georgia 30333, United States

4. Source(s) of financing of the reported activity, including indication if the activity is wholly or partly financed by the Ministry of Defence.

Centers for Disease Control and Prevention (CDC) U.S. Department of Health and Human Services (HHS) U.S. Department of Homeland Security (DHS) U.S. Agency For International Development (USAID) U.S. Department of State (DoS) U.S. Department of Defense (DOD) - partly

5. Number of maximum containment units3 within the research centre and/or laboratory, with an indication of their respective size (m2).

BSL 4 Laboratory 136 m2 BSL 4 Laboratory 271 m2

BSL 4 Laboratory 136 m2

6. Scope and general description of activities, including type(s) of microorganisms and/or toxins as appropriate.

Activities include developing diagnostic assays for public health, conducting molecular and antigenic characterization of microorganisms, determining pathogenicity and virulence of infectious agents, determining natural history of infectious organisms, and conducting epidemiologic studies and surveillance for diseases. Biodefense activities include those with select agents (the select agents list is available at: http://www.selectagents.gov/Select%20Agents%20and%20Toxins%20List.html).

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Form A, Part 1 (i)

Exchange of data on research centres and laboratories1

1. Name(s) of facility2.

National Institutes of Health (NIH), NIAID-Rocky Mountain Laboratories [Declared in accordance with Form A, Part 2 (iii)]

2. Responsible public or private organization or company.

National Institutes of Health U.S. Department of Health and Human Services

3. Location and postal address.

903 South 4th Street Hamilton, Montana 59840

United States

4. Source(s) of financing of the reported activity, including indication if the activity is wholly or partly financed by the Ministry of Defence.

U.S. Department of Health and Human Services (HHS)

5. Number of maximum containment units3 within the research centre and/or laboratory, with an indication of their respective size (m2).

BSL 4 Laboratory 1145 m2

6. Scope and general description of activities, including type(s) of microorganisms and/or toxins as appropriate.

Research activities involving viruses, bacteria, rickettsiae, prions, and toxins revolve around pathogenesis studies, vaccinology, and development of therapeutic agents and rapid diagnostic assays in support of the civilian biodefense program.

Additional information can be found at:

http://www.niaid.nih.gov/about/pages/default.aspx

http://www.niaid.nih.gov/about/organization/dir/rml/Pages/default.aspx

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Form A, Part 1 (i)

Exchange of data on research centres and laboratories1

1. Name(s) of facility2.

Galveston National Laboratory (GNL) Complex including Robert E. Shope Laboratory

2. Responsible public or private organization or company.

The University of Texas Medical Branch

3. Location and postal address.

301 University Blvd. Galveston, Texas 77555

United States

4. Source(s) of financing of the reported activity, including indication if the activity is wholly or partly financed by the Ministry of Defence.

Universities U.S. Department of Agriculture (USDA) Private Foundations Pharmaceutical Industry U.S. Department of Energy (DOE) U.S. Department of Defense (DOD) - partly U.S. Department of Homeland Security (DHS) National Institutes of Health (NIH)

5. Number of maximum containment units3 within the research centre and/or laboratory, with an indication of their respective size (m2).

BSL 4 Laboratory 186 m2 Shope Laboratory BSL 4 Laboratory 1022 m2 GNL Laboratory

6. Scope and general description of activities, including type(s) of microorganisms and/or toxins as appropriate.

The mission of the Galveston National Laboratory is to assist the National Institute of Allergy and Infectious Diseases and the nation in the development of an improved means for the prevention, diagnosis and treatment of potentially life-threatening diseases caused by naturally emerging and purposefully disseminated infectious agents. To accomplish this

Page 10 of 237 goal GNL conducts multidisciplinary research into the causes, modes of transmission, and mechanisms of infectious diseases. Studies focus on a number of pathogens requiring BSL- 4 containment, primarily those that cause viral hemorrhagic fevers, as well as some zoonotic viruses requiring enhanced BSL-3 containment. Products likely to emerge from research and investigations within the GNL include novel diagnostic assays, improved therapeutics and treatment models, and preventative measures such as vaccines.

Additional information can be found at: http://www.utmb.edu/gnl/

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Form A, Part 1 (i)

Exchange of data on research centres and laboratories1

1. Name(s) of facility2.

The Betty Slick and Lewis J. Moorman, Jr. Laboratory Complex, Department of Virology and Immunology

2. Responsible public or private organization or company.

Texas Biomedical Research Institute

3. Location and postal address.

P.O. Box 760549 San Antonio, Texas 78245-0549

United States

4. Source(s) of financing of the reported activity, including indication if the activity is wholly or partly financed by the Ministry of Defence.

National Institutes of Health (NIH) U.S. Department of Defense (DOD) - partly U.S. Department of Homeland Security (DHS)

Private Sector Companies Private Donors

5. Number of maximum containment units3 within the research centre and/or laboratory, with an indication of their respective size (m2).

BSL 4 Laboratory 114 m2

6. Scope and general description of activities, including type(s) of microorganisms and/or toxins as appropriate.

The mission of the Laboratory is to develop vaccines and therapeutics against viral pathogens, and to determine how viruses replicate and spread. Scientists are studying new and emerging disease threats, possible bioterrorism agents, and as-yet uncharacterized agents for biodefense. TXBiomed (formerly Southwest Foundation for Biomedical

Research) has permits from the U.S. Department of Agriculture and the Centers for Disease Control to work on select agents. Additional information can be found at: http://www.TXBiomed.org.

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Form A, Part 1 (i)

Exchange of data on research centres and laboratories1

1. Name(s) of facility2.

Viral Immunology Center - National B Virus Resource Laboratory

2. Responsible public or private organization or company.

Georgia State University

3. Location and postal address.

P. O. Box 4118 Atlanta, Georgia 30302-4118

United States

4. Source(s) of financing of the reported activity, including indication if the activity is wholly or partly financed by the Ministry of Defence.

National Institutes of Health (NIH) Georgia Research Alliance Immunology Core Support Elizabeth R. Griffin Research Foundation

5. Number of maximum containment units3 within the research centre and/or laboratory, with an indication of their respective size (m2).

BSL 4 Laboratory 60 m2

6. Scope and general description of activities, including type(s) of microorganisms and/or toxins as appropriate.

The Viral Immunology Center provides a global resource to assist in the identification of zoonotic disease transmissions and to develop enhanced strategies to detect viral infections in macaques. Current projects in the National B Virus Resource Laboratory are focused on the molecular biology of human and non-human primate alphaherpesviruses and the diseases they cause. Studies focus on the mechanisms by which virus kills the host and how that process can be circumvented with:

 Early identification - research focuses on the design and development of new

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approaches to more effectively identify these agents in both natural and foreign hosts;  Appropriate antiviral drugs - researchers continually screen the efficacy of existing as well as novel antiviral agents to inhibit the growth of viruses that can potentially cross into the human population, either through occupational exposure or through more subtle contact; and  In the future, effective vaccines.

Additional information can be found at http://www2.gsu.edu/~wwwvir/Research/Index.html

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Form A, Part 2(i)

BWC - Confidence Building Measure

National biological defence research and development programmes - Declaration

United States of America

April 15, 2013

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Form A, Part 2 (i)

National biological defence research and development programme declaration:

Declaration

Are there any national programmes to conduct biological defence research and development within the territory of the State Party, under its jurisdiction or control anywhere? Activities of such programmes would include prophylaxis, studies on pathogenicity and virulence, diagnostic techniques, aerobiology, detection, treatment, toxinology, physical protection, decontamination and other related research.

Yes X No

If the answer is Yes, complete Form A, part 2 (ii) which will provide a description of each programme.

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Form A, Part 2 (ii)

BWC - Confidence Building Measure

National biological defence research and development programmes - Description

United States of America

April 15, 2013

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Form A, Part 2 (ii)

National biological defence research and development programmes

Description

The United States Government conducts a broad effort to reduce the risks presented by the deliberate or accidental release of biological agents and to defend against those threats in the event they occur. As called for by the National Strategy for Countering Biological Threats, this encompasses a range of initiatives, including improving global access to the life sciences to combat infectious disease regardless of its cause; establishing and reinforcing norms of safe and responsible conduct within the life sciences; improving capacity to detect and respond to outbreaks as they occur; and instituting a suite of coordinated activities that collectively help to influence, identify, inhibit, and/or interdict those who seek to misuse the life sciences.

One key element of this effort is the U.S. biodefense enterprise, which itself includes a variety of research and development programs aimed at protecting against the deliberate use of biological materials to cause harm. These programs focus on the identification of harmful pathogens and outbreaks of infectious diseases and their containment, treatment, and elimination from the environment. These programs are managed by several agencies with direct stakes in national security, environmental protection, and human and animal health and safety, including the Departments of Agriculture, Defense, Energy, Health and Human Services, Homeland Security, and the Environmental Protection Agency.

Historically, certain pathogens were selected for use as biological weapons because of their pathogenicity. Research on these pathogens, including study of molecular mechanisms and related diagnostic, vaccine and therapeutic development work, not only increases U.S. biodefense preparedness, but offers inherent benefits for broader public health needs. Efforts to improve medical product stability, potency and ease-of-use that cut across disease targets could yield significant benefits for public health systems that cannot support existing treatments that require refrigeration, multiple doses or sophisticated diagnostic techniques. Similarly, biodefense initiatives to improve human and animal host defenses, to monitor emerging infectious diseases and drug-resistant microbes, and to clean up the site of a biological weapons attack have civilian applications that benefit public health services, such as epidemiological disease surveillance and environmental remediation.

To promote the benefits gained by these programs and to ensure that the research is available to the scientific community both domestically and internationally, the United States Government encourages the publication of research funded by its biodefense programs.

For more information on U.S. Government strategies related to biodefense, including biological threat preparedness and response, please consult:

 Management of Domestic Incidents (Homeland Security Presidential Directive 5 [HSPD- 5]) and the related National Response Framework;  Presidential Policy Directive 8: National Preparedness (PPD-8);

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 National Strategy for Defense of United States Agriculture and Food (HSPD-9);  National Biodefense Strategy (HSPD-10/National Security Presidential Directive-33 [NSPD-33]);  Medical Countermeasures against Weapons of Mass Destruction (HSPD-18);  Public Health and Medical Preparedness (HSPD-21);  National Strategy to Combat Weapons of Mass Destruction (NSPD-17/HSPD-4);  Executive Order 13527 (“Establishing Federal Capabilities for the Timely Provision of Medical Countermeasures following a Biological Attack”); and  National Strategy for Countering Biological Threats.

The National Strategy for Countering Biological Threats is available at: http://www.whitehouse.gov/sites/default/files/National_Strategy_for_Countering_BioThreats.pdf

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Form A, Part 2 (ii)

National biological defence research and development programmes

Description

1. State the objectives and funding of each programme and summarize the principal research and development activities conducted in the programme. Areas to be addressed shall include: prophylaxis, studies on pathogenicity and virulence, diagnostic techniques, aerobiology, detection, treatment, toxinology, physical protection, decontamination and other related research.

The Department of Defense Biological Defense Program provides support and world-class capabilities to protect the U.S. Armed Forces against biological warfare threats and emerging infectious diseases. The Program supports a comprehensive strategic framework to improve biological defense preparedness, reduce risk to the nation, and field the appropriate mix of defensive capabilities for sustained military operations with minimum degradation of combat effectiveness attributed to current biological hazards and emerging threats.

The Program works to protect the nation from biological threats by providing medical countermeasure capabilities, building on current strengths but recognizing a changing environment. This includes an agile and flexible national capability and capacity to produce medical countermeasures rapidly to counter known or unknown threats, including novel and naturally occurring emerging infectious diseases. Current research focuses on a recombinant botulinum vaccine, a recombinant vaccine against pneumonic plague, medical countermeasures against hemorrhagic fever viruses, test and evaluation of medical countermeasures against biological threat/terrorism agents, and the advanced development and licensure of other vaccines and biological products designed to protect against a variety of biological agents.

The Program also works on producing self-disinfecting and/or self-decontaminating materials as well as developing, producing, and fielding a system for sampling, detecting, and identifying biological agents.

Biological defense-related work conducted by the Department of Defense is carried out by the military services and biological defense program-focused agencies. These include funding agencies and service laboratories within the Departments of the Air Force, Army, and Navy, and the Defense Threat Reduction Agency (DTRA)/Joint Science and Technology Office (JSTO), the Joint Program Executive Office (JPEO) for Chemical and Biological Defense, and the Defense Advanced Research Projects Agency (DARPA).

2. State the total funding for each programme and its source.

$825,400,000 U.S. Department of Defense (DOD)

3. Are aspects of these programmes conducted under contract with industry, academic

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institutions, or in other non-defence facilities?

Yes

4. If yes, what proportion of the total funds for each programme is expended in these contracted or other facilities?

55 %

5. Summarize the objectives and research areas of each programme performed by contractors and in other facilities with the funds identified under paragraph 4.

 Provide support and world-class capabilities to protect the U.S. Armed Forces against biological warfare threats and emerging infectious diseases  Development of medical countermeasure capabilities  Development of vaccines and therapeutics  Development of self-disinfecting and/or self-decontaminating materials

 Testing of detection and identification methods, protective equipment, and decontamination systems  Development and testing of biological diagnostic detection systems

6. Provide a diagram of the organizational structure of each programme and the reporting relationships (include individual facilities participating in the programme).

7. Provide a declaration in accordance with Form A, part 2 (iii) for each facility, both

Page 21 of 237 governmental and non-governmental, which has a substantial proportion of its resources devoted to each national biological defence research and development programme, within the territory of the reporting State, or under its jurisdiction or control anywhere.

In accordance with Form A part 2 (iii): • Air Force Research Laboratory (AFRL), Materials and Manufacturing Directorate • Lothar Salomon Test Facility (LSTF) • Naval Medical Research Center (NMRC) • Naval Research Laboratory (NRL) Naval Surface Warfare Center-Dahlgren Division Chemical, Biological, Radiological • (CBR) Defense Laboratory • Tyndall Air Force Base (AFB) -- 1 • Tyndall Air Force Base (AFB) -- 2 • U.S. Army Medical Research Institute of Chemical Defense (USAMRICD) • U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) • U.S. Army Edgewood Chemical and Biological Center

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Form A, Part 2 (ii)

National biological defence research and development programmes

Description

The Environmental Protection Agency (EPA)'s mission is to protect public health and the environment. The National Homeland Security Research Center (NHSRC), part of the EPA's Office of Research and Development, conducts and reports on research to improve capacity to respond to and recover from environmental contamination of water infrastructure, buildings and outdoor areas by chemical, biological, radiological and nuclear (CBRN) agents. The NHSRC biodefense program focuses on EPA's two biodefense responsibilities: 1) assistance in the protection of the American water supply, and 2) decontamination of indoor and outdoor areas should the U.S. suffer a contamination incident.

EPA is designated as the government's lead sector-specific agency for water, and is responsible for protecting water systems and detecting and recovering from terrorist attacks

affecting them. EPA's homeland security research is responsible for developing products and providing expertise to protect, detect, respond to, and recover from terrorist attacks on the nation's water and wastewater infrastructure.

EPA is also the lead federal agency for the remediation of areas contaminated by terrorist events involving the release of biological organisms, biotoxins, chemical warfare agents, toxic industrial chemicals, toxic industrial materials, and radiological materials. Terrorist acts may involve biological, chemical, and radiological agents not previously encountered as environmental pollutants. EPA's homeland security research is responsible for providing procedures and methods that will assist EPA's responders in the detection and containment of contamination, and in the remediation of sites following terrorist attacks.

2. State the total funding for each programme and its source.

$7,800,000 U.S. Environmental Protection Agency (EPA)

3. Are aspects of these programmes conducted under contract with industry, academic institutions, or in other non-defence facilities?

Yes

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4. If yes, what proportion of the total funds for each programme is expended in these contracted or other facilities?

31 %

5. Summarize the objectives and research areas of each programme performed by contractors and in other facilities with the funds identified under paragraph 4.

NHSRC has research being conducted by contractors to assess risks of biological agents. Exposure studies are being conducted to estimate doses that result in adverse health effects from biological hazards. To address the need for remediating contaminated sites, NHSRC has been evaluating as well as developing analytical methods for biological agents.

6. Provide a diagram of the organizational structure of each programme and the reporting relationships (include individual facilities participating in the programme).

7. Provide a declaration in accordance with Form A, part 2 (iii) for each facility, both governmental and non-governmental, which has a substantial proportion of its resources devoted to each national biological defence research and development programme, within the territory of the reporting State, or under its jurisdiction or control anywhere.

Not Applicable

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Form A, Part 2 (ii)

National biological defence research and development programmes

Description

Improving our nation's defenses against bioterrorism is a key part of the U.S. Government's homeland security effort. The Department of Health and Human Services (HHS) supports activities to improve local and state public health systems, to expand existing biosurveillance efforts, and to fund research on medical countermeasures against potential bioterror agents.

The National Institutes of Health (NIH) biodefense program is supported by funding from the U.S. Department of Health and Human Services. The NIH, and specifically the National Institute of Allergy and Infectious Diseases (NIAID), has the primary responsibility within the U.S. Government for civilian biodefense research. The intent of the program is to provide countermeasures to be used to protect the U.S. civilian population through the development of vaccines, therapeutic agents and rapid, agent-specific assays.

2. State the total funding for each programme and its source.

$61,677,586 U.S. Department of Health and Human Services (HHS)

3. Are aspects of these programmes conducted under contract with industry, academic institutions, or in other non-defence facilities?

4. If yes, what proportion of the total funds for each programme is expended in these contracted or other facilities?

Not Applicable

5. Summarize the objectives and research areas of each programme performed by contractors and in other facilities with the funds identified under paragraph 4.

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Not Applicable

6. Provide a diagram of the organizational structure of each programme and the reporting relationships (include individual facilities participating in the programme).

In accordance with Form A part 2 (iii): National Institutes of Health (NIH), C.W. Bill Young Center for Biodefense and • Emerging Infectious Diseases

• National Institutes of Health (NIH), Dale and Betty Bumpers Vaccine Research Center • Integrated Research Facility (IRF) - Rocky Mountain Laboratories (RML)

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Form A, Part 2 (ii)

National biological defence research and development programmes

Description

The objective of the Mass Spectrometry Toxin Laboratory and the Chemical Threats Method Development Laboratory within CDC's National Center for Environmental Health, Division of Laboratory Sciences is to develop toxin assays that are critical for better detection and diagnosis during a public health response to biological toxins.

2. State the total funding for each programme and its source.

$2,497,544 Centers for Disease Control and Prevention (CDC)

3. Are aspects of these programmes conducted under contract with industry, academic institutions, or in other non-defence facilities?

4. If yes, what proportion of the total funds for each programme is expended in these contracted or other facilities?

Not Applicable

5. Summarize the objectives and research areas of each programme performed by contractors and in other facilities with the funds identified under paragraph 4.

Not Applicable

6. Provide a diagram of the organizational structure of each programme and the reporting relationships (include individual facilities participating in the programme).

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In accordance with Form A part 2 (iii): CDC, National Center for Environmental Health (NCEH), Division of Laboratory Sciences • (DLS)

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Form A, Part 2 (ii)

National biological defence research and development programmes

Description

The activities of the CDC Office of Infectious Disease (OID) include developing diagnostic assays for public health, conducting molecular and antigenic characterization of microorganisms, evaluating decontamination methods, determining pathogenicity and virulence of infectious agents, determining the natural history of infectious organisms, and conducting epidemiologic studies and surveillance for diseases. Biodefense activities include those with select agents. OID includes the National Center for Emerging Zoonotic

Infectious Diseases (NCEZID) and the National Center for Immunization and Respiratory Diseases (NCIRD).

The select agents list is available at: http://www.selectagents.gov/Select%20Agents%20and%20Toxins%20List.html

2. State the total funding for each programme and its source.

$22,656,144 Centers for Disease Control and Prevention (CDC)

3. Are aspects of these programmes conducted under contract with industry, academic institutions, or in other non-defence facilities?

Yes

4. If yes, what proportion of the total funds for each programme is expended in these contracted or other facilities?

5 %

5. Summarize the objectives and research areas of each programme performed by contractors and in other facilities with the funds identified under paragraph 4.

Vaccine efficacy trials, reagent development, bioterrorism preparedness and response

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activities, avian influenza preparedness, and disease surveillance in CDC field locations.

6. Provide a diagram of the organizational structure of each programme and the reporting relationships (include individual facilities participating in the programme).

In accordance with Form A part 2 (iii): CDC, OID, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), • Division of Vector Borne Diseases (DVBD) - Ft. Collins • CDC, Office of Infectious Diseases (OID)

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Form A, Part 2 (ii)

National biological defence research and development programmes

Description

U.S. Department of Agriculture (USDA)

Background

Foreign animal diseases represent a major threat to U.S. agriculture. Introduction of these agents, either accidental or deliberate, has devastating social and economic effects not only in the country's agricultural systems but also in a wide range of economic activities. Diseases of concern include but are not limited to Foot-and-Mouth Disease, Avian Influenza, Rift Valley Fever, Classical Swine Fever, African Swine Fever, Exotic Newcastle disease, Vesicular stomatitis, and Exotic Bluetongue.

Animal health officials define an exotic or foreign animal disease (FAD) as an important transmissible livestock or poultry disease believed to be absent from the U.S. and its territories that has a potential significant health or economic impact. Foreign animal diseases are considered a threat to the U.S. when they significantly affect human health or animal production and when there is an appreciable cost associated with disease control and eradication efforts. To protect the long-term health and profitability of U.S. animal agriculture, incursions of a FAD must be rapidly controlled.

In the U.S., control usually means disease eradication. Disease eradication is currently accomplished by eliminating the animal, resulting in loss of protein, loss of income to the farm community, public opposition and environmental disruption. In addition to control costs, one of the most immediate and severe consequences of a FAD occurrence in the U.S. will be the loss of export markets. Many new issues and factors are affecting FAD prevention, control, management, and recovery. These factors include free trade agreements, free trade blocks, regionalization, increased international passenger travel, intensification of animal production, the constant evolution of infectious agents, and the uncertain impact of biotechnology and bioterrorism.

Current methods for prevention and control of high consequence diseases, including prevention, detection, control and eradication, are not socially or economically acceptable. Rapid detection and characterization tools for prevention, control and eradication of foreign

Page 31 of 237 animal diseases are inadequate or not currently available. Our understanding of pathogenesis, transmission, and immune response is insufficient to rapidly control and eradicate foreign animal diseases. Effective measures to prevent, control and eradicate foreign animal diseases are lacking or inadequate.

Strategic Objectives

 Establish Agriculture Research Service (ARS) laboratories into a fluid, highly effective research network, to maximize use of core competencies and resources.  Access to specialized high containment facilities to study zoonotic and emerging diseases.  Develop an integrated animal and microbial genomics research program.  Establish centers of excellence in animal immunology.  Launch a biotherapeutic discovery program providing alternatives to animal drugs.  Build a technology-driven vaccine and diagnostic discovery research program.  Develop core competencies in field epidemiology and predictive biology.  Develop internationally recognized OIE expert collaborative research laboratories.  Establish best in class training center for our nation's veterinarians and scientists.  Develop a model technology transfer program to achieve the full impact of our research discoveries.

Research Needs

In order to control foreign animal disease, a wide variety of agent detection platforms need to be developed and validated. Information for design of these platforms will come in part from further knowledge of pathogen genomics and proteomics and in part from understanding the evolution and genetic variability of disease agents. Although many of the foreign animal diseases have existed for many years in other countries, more fundamental knowledge of these agents is required. There is still a lack of understanding in host range and tissue tropism, carrier state, duration and routes of shedding, transmission mechanisms, (e.g., vectors, fomites, aerosols), ecology and epidemiology (e.g., wildlife reservoirs). If these diseases should occur in the U.S., more effective prevention and control tools, such as identifying suitable control strategies compatible with short time and cost of recovery from disease outbreaks (DIVA compatible), need to be developed. There is a need for development of vaccines and biotherapeutics suitable for strategic stockpiles and integrated methods of disease control, including vector control and animal management, which all lead to a better capability to regain disease-free status for the country and retain economic sustainability.

Expected Outputs:

 Better anticipation of introduction of foreign animal diseases.  Capability to advise regulatory officials on scientific procedures for the prevention of introduction of FADs.

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 Better capability to produce effective products to control and eliminate foreign animal diseases.  Real-time detection of agents in a wide range of farm matrices.  Searchable databases of genome and proteome information for major known FAD agents.  Improved ability to predict or anticipate emergence or introduction of FAD agents.  Discovery of effective candidate biotherapeutics.  Discovery of effective candidate vaccines that allow differentiation of infected animals from vaccinated animals (DIVA).  Viable integrated vector control strategies that minimize losses.

The USDA-ARS biodefense research program is intramural and implemented in ARS high containment facilities in the following locations: Ames, Iowa; Orient Point, New York; Athens, Georgia; Frederick, Maryland.

2. State the total funding for each programme and its source.

$17,022,000 U.S. Department of Agriculture (USDA)

3. Are aspects of these programmes conducted under contract with industry, academic institutions, or in other non-defence facilities?

4. If yes, what proportion of the total funds for each programme is expended in these contracted or other facilities?

Not Applicable

5. Summarize the objectives and research areas of each programme performed by contractors and in other facilities with the funds identified under paragraph 4.

Not Applicable

6. Provide a diagram of the organizational structure of each programme and the reporting relationships (include individual facilities participating in the programme).

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In accordance with Form A part 2 (iii): • Foreign Disease-Weed Science Research Unit • Plum Island Animal Disease Center (PIADC)

• Southeast Poultry Research Laboratory • National Animal Disease Center (NADC)

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Form A, Part 2 (ii)

National biological defence research and development programmes

II. Description

1. State the objectives and funding of the programme and summarize the principal research and development activities conducted in the programme. Areas to be addressed shall include: prophylaxis, studies on pathogenicity and virulence, diagnostic techniques, aerobiology, detection, treatment, toxicology, physical protection, decontamination and other related research.

The Biological Countermeasures Program in the Science and Technology (S&T) Directorate of the Department of Homeland Security (DHS) is broken into three research and development categories (Bioagent Detection, Bioagent Threat Assessment, and Bioagent Attack Resiliency) and focuses emerging science and technology to provide the understanding, technologies, and systems needed to protect against biological attacks on the U.S. population, agriculture or infrastructure. The program focuses on research, development, testing, and evaluation (RDT&E) and on the transition to deployment of the needed technologies and systems. The five main areas of study are: 1) systems studies and decision support tools, 2) threat awareness, 3) surveillance and detection research and development (R&D), 4) forensics, and 5) response and restoration. The program supports other U.S. federal agencies in overall coordination of national biodefense efforts.

Efforts conducted during 2012 include risk assessments, biodefense knowledge management, biological warning and detection systems for critical infrastructure and urban areas, decontamination of transit systems, and national bioforensic analysis. Efforts at the National Biodefense Analysis and Countermeasures Center (NBACC) included biological threat characterization, development of response plans and risk communication; and at the Plum Island Animal Disease Center, development of vaccines and diagnostics for foreign animal diseases.

The DHS Compliance Review Group, chaired by the DHS Deputy Secretary, reviews all DHS- funded biological defense projects for compliance with the provisions of the Biological Weapons Convention and associated U.S. domestic laws and policies.

2. State the total funding for the programme and its source.

$77,160,000 U.S. Department of Homeland Security (DHS)

3. Are aspects of the programme conducted under contract with industry, academic institutions, or in other non-defence facilities?

Yes

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4. If yes, what proportion of the total funds for the programme is expended in these contracted or other facilities?

100 %

5. Summarize the objectives and research areas of the programme performed by contractors and in other facilities with the funds identified in paragraph 4.

The Biological Countermeasures program utilizes multiple activities to carry out its mission. For threat awareness, efforts are underway to characterize threats posed by biological weapons, anticipate future threats, and conduct comprehensive threat and risk assessments to guide prioritization of the Nation's biodefense investments. One such ongoing effort, Project Bioshield, seeks to develop modern, effective medical countermeasures to protect the population against attack by chemical, biological, radiological, or nuclear weapons.

Within the area of surveillance and detection R&D, performers are developing next- generation detectors for biological threat agents, including fully autonomous detection capabilities for the third generation (Gen 3) BioWatch system. In addition, other efforts are underway to develop the assays needed for detectors to accurately recognize a biological agent (i.e., signatures or fingerprints of biological agents). Another focus is on developing detect-to-protect systems specifically for use indoors as well as detection systems for protecting food products.

Under forensics, funding is devoted to operate the National BioForensics and Analysis Center (NBFAC) and conduct bioforensics research in support of criminal investigations and attribution by the appropriate Federal agency. These activities provide facilities, tools (i.e., assays, protocols, and strain libraries), analyses, and rigorous chain-of-custody controls needed to support the FBI and others in their investigation of potential biocrimes or acts of bioterrorism.

Lastly, the Biological Countermeasures program has a response and restoration element that provides advanced planning, develops concepts-of-operation, and funds exercises and training for responding to and recovering from large-scale biological attacks. Biological agents have the potential to contaminate large portions of a city, covering multiple city blocks and facilities therein. The objective is to provide a more rapid and less expensive post-attack cleanup and restoration in such situations. This program is developing a systems approach for the restoration of citywide areas and of critical facilities, such as major transportation hubs; it is not developing specific decontamination technologies. Restoration demonstrations, which bring together Federal, State, and local partners to develop, test, and then share the concepts-of-operations for key scenarios, are at the heart of this approach.

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6. Provide a diagram of the organizational structure of the programme and the reporting relationships (include individual facilities participating in this programme).

7. Provide a declaration in accordance with Form A part 2 (iii) for each facility, both governmental and non-governmental, which has a substantial proportion of its resources devoted to the national biological defence research programme, within the territory of the reporting State, or under its jurisdiction or control anywhere.

In accordance with Form A Part 2(iii):  National Biodefense Analysis and Countermeasures Center (NBACC)  Plum Island Animal Disease Center (PIADC)

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Form A, Part 2 (iii)

BWC - Confidence Building Measure

National biological defence research and development programmes - Facilities

United States of America

April 15, 2013

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Form A, Part 2 (iii)

National biological defence research and development programme

To maintain our existing high level of transparency to States Parties, we are making available, to all States Parties, information on microorganisms and toxins consistent with previous submissions.

The U.S. Government identified potential concerns associated with public release of information on the identity of microorganisms and toxins at specific facilities.

To balance these concerns with a desire to promote transparency, in Form A, Part 2 (iii) the U.S. submission characterizes the agents used for biological defense research at each facility by identifying:

 whether there are Biological Select Agent and Toxins (Select Agents) present at the facility, and if so, which subcategories (HHS, Overlap, USDA, and USDA Plant Protection and Quarantine [PPQ]) are represented;  for each Select Agent subcategory, whether these agents are also listed under NIAID Category A, B, or C Priority Pathogens;  whether there are non-Select Agent NIAID Category A, B or C Priority Pathogens present at the facility; and  other relevant information as appropriate.

Biological Select Agents and Toxins (Select Agents) are biological agents or toxins that have the potential to pose a severe threat to public, animal or plant health, or to animal or plant products, whose possession, use and transfer are regulated by the Select Agent Rules. Additional information on Select Agents can be found at: http://www.selectagents.gov.

The NIAID list of Category A, B and C Priority Pathogens identifies specific pathogens as priorities for additional research efforts as part of the NIAID biodefense research agenda.

Additional information on NIAID Category A, B and C Priority Pathogens can be found at: http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/Pages/CatA.aspx http://pathema.jcvi.org/pathema/AbcGenomes.shtml http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/Documents/categorybandc.pdf

Using the Select Agent and NIAID lists to categorize the agents at a facility offers greater transparency into the types of agents than using either list alone. Lists of Biological Select Agents and Toxins, and NIAID Category A, B, C Priority Pathogens can be found in Appendix A. A compiled list of microorganisms and toxins used for biological defense research at the facilities reported in Form A, Part 2 (iii) can be found in Appendix B.

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Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

National Biodefense Analysis and Countermeasures Center (NBACC)

2. Where is it located (provide both address and geographical location)?

8300 Research Plaza Fort Detrick, Maryland 21702

3. Floor area of laboratory areas by containment level:

BL2 1282 (sqM) BL3 2564 (sqM) BL4 980 (sqM) Total laboratory floor area 4826 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 143

(ii) Division of personnel:

Military 0

Civilian 143

(iii) Division of personnel by category:

Scientists 23

Engineers 30

Technicians 47

Administrative and support staff 43

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Aerobiology, Bacteriology, Biochemistry, Bioinformatics, Biology, Biomedical Science, Biophysics, Biotechnology, Cell Biology, Chemistry, Computer Science, Genetics, Immunology, Molecular Biology, Molecular Pathogenic Microbiology, Toxicology, Veterinary Medicine, Virology

Page 40 of 237

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 143

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Homeland Security (DHS) U.S. Department of Justice (DOJ)

U.S. Department of Defense (DOD) - partly

(vii) What are the funding levels for the following program areas:

Research $ 3,033,517 Development $ 6,579,127 Test and evaluation $ 0 Total $ 9,612,644

(viii) Briefly describe the publication policy of the facility:

The NBACC publication policy is to present research results to the greater scientific community as widely as possible. As a Federally Funded Research and Development Center engaged in research with select agents/regulated pathogens, NBACC has established a formal, multi-tiered review system to ensure compliance and conformance with U.S. Government regulations including export control regulations under EAR/ITAR, the

Biological Weapons Convention (BWC), and internal U.S. Department of Homeland Security (DHS) policies. Prior to submittal to journals or release, all publications are reviewed by NBACC and DHS for security, clarity and accuracy with regard to the description of the work.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

1. Dabisch, P., Bower, K., Dorsey, B., Wronka, L. Recovery efficiencies for Burkholderia thailandensis from various aerosol sampling media. Front Cell Infect Microbiol. 2012; 2: 78. 2. Koren, S., Schatz, M.C., Walenz, B.P., Martin, J., Howard, J.T., Ganapathy, G., Wang, Z., Rasko, D.A., McCombie, W.R., Jarvis, E.D., Phillippy, A.M., Hybrid Error Correction and De Novo Assembly of Single-Molecule Sequencing Reads. Nature Biotechnology; July 2012; http://www.nature.com/doifinder/ 10.1038/nbt.2280. 3. Motley, S.T., Redden, C.L., Eshoo, M.W., Burans, J.P., Rosovitz, M.J., Differentiating

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real-time PCR products using electron-spray ionization mass spectrometry for microbial forensics. Journal of Diagnostic Microbiology and Infectious Disease (August 2011 submitted) 4. Ondov, B., Bergman, N.H., Phillippy, A.M. Interactive visualization of hierarchal information for metagenomics; BMC Bioinformatics 2011, 12:385, 30 September 2011. 5. Price, E.P, Seymour, M.L., Sarovich, D.S., Latham, J., Wolken, S.R., Mason, J., Vincent, G., Drees, K.P, Beckstrom-Sternberg, S.M., Phillippy, A.M., Koren, S., Okinaka, R.T., Chung, W.K., Schupp, J.M., Wagner, D.M., Vipond, R., Foster, J.T., Bergman, N.H., Burans. J., Pearson, T., Brooks, T., Keim, P., The Molecular Epidemiologic Investigation of an Anthrax Outbreak in European Heroin Users. Emerging Infectious Diseases. 2012: 18(8):1307-1313 6. Roof, S., Diviak, L., Karaolis, D.K.R., Wiedmann, M., Development of automated ribotyping protocols for Bacillus anthracis. Journal of Clinical Microbiology; (July 2011 submitted) 7. Salzberg, S.L., Phillippy, A.M., Zimin, A., Puiu, D., Magoc, T., Koren, S., Treangen, T., Schatz, M., Delcher, A.L., Roberts, M., Marcais, G., Pop, M., Yorke, J. A., GAGE: A Critical Evaluation of Genome Assemblies and Assembly Algorithms. Genome Research; Mar;22(3):557-67. Epub January 6, 2012.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: The NBACC mission is to provide the nation with the scientific basis for characterization of biological threats and bioforensic analysis to support attribution investigations. NBACC conducts studies to fill in information gaps to better understand current and future biological threats; to assess vulnerabilities; and to determine potential impacts to guide the development of biological countermeasures such as detectors, drugs, vaccines, and decontamination technologies. When needed, NBACC conducts experimental programs to better characterize the benefits and risks of changes in U.S. biodefense preparations. NBACC also develops bioforensic assays and provides operational bioforensic analysis to support the attribution of biocrime and bioterrorism.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A, B and C Priority Pathogens

• Overlap Select Agents

4 Including viruses and prions. Page 42 of 237

Including NIAID Category A, B and C Priority Pathogens

• USDA Select Agents and Toxins Including NIAID Category A and B Priority Pathogens

• Other pathogens or toxins Including non-Select Agent, NIAID Category A, B and C Priority Pathogens

(iii) Outdoor Studies: None

Page 43 of 237

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Plum Island Animal Disease Center (PIADC)

2. Where is it located (provide both address and geographical location)?

40550 Route 25 Orient Point, New York 11957

3. Floor area of laboratory areas by containment level:

BL2 292 (sqM) BL3 18046 (sqM) BL4 0 (sqM) Total laboratory floor area 18338 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 385

(ii) Division of personnel:

Military 0

Civilian 385

(iii) Division of personnel by category:

Scientists 97

Engineers 2

Technicians 21

Administrative and support staff 265

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Biology, Chemistry, Engineering, Microbiology, Molecular Biology, Molecular, Computational Biology, Pathology, Research Facility Operations, Veterinary Medicine

(v) Are contractor staff working in the facility? If so, provide an approximate number.

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Yes Number: 265

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Agriculture (USDA) U.S. Department of Homeland Security (DHS)

(vii) What are the funding levels for the following program areas:

Research $ 4,000,000 Development $ 11,000,000 Test and evaluation $ 5,000,000 Total $ 20,000,000

(viii) Briefly describe the publication policy of the facility:

DHS scientific research staff is expected to publish papers in open literature. Papers are peer reviewed and approved by PIADC and DHS for security, clarity, and accuracy with regard to the description of work prior to submittal to journals or release.

USDA Agricultural Research Service (ARS) has several publication policies:

 Policy Number 150.1 "Dissemination of Public Information by ARS"

http://www.afm.ars.usda.gov/ppweb/PDF/150-01.pdf  Number 113.1 "Publishing (Print and Electronic) (www.afm.ars.usda.gov/ppweb/2010/113-1-ARS.pdf); and  Number 152.1 "Procedures for Publishing Manuscripts and Abstracts with Non-USDA Publishers (Outside Publishing) (http://www.afm.ars.usda.gov/ppweb/pdf/152-01.pdf)

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Animal and Plant Health Inspection Service (APHIS) Publications in 2012 1. Deng, M.Y., Millien, M., Jacques-Simon, R., Flanagan, J.K., Bracht, A.J., Carrillo, C., Barrette, R.W., Fabian, A., Mohamed, F., Moran, K., Rowland, J., Swenson, S.L., Jenkins-Moore, M., Koster, L., Thomsen, B.V., Mayr, G., Pyburn, D., Morales, P., Shaw, J., Burrage, T., White, W., Mcintosh, M.T., Metwally, S. 2012. Diagnosis Of Teschovirus Encephalomyelitis In The Republic Of Haiti. Journal of Veterinary Diagnostic Investigation. 24(4): 671-678. 2. Das, A., Babiuk, S., Mcintosh, M.T. 2012. Development Of A Loop-Mediated

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Isothermal Amplification Assay For Rapid Detection Of Capripoxviruses. Journal of Clinical Microbiology. 50 (5):1613-1620. 3. Donahue, B.C., Petrowski, H.M., Melkonian, K., Ward, G.B., Mayr, G.A., Metwally, S. 2012. Analysis Of Clinical Samples For Early Detection Of Classical Swine Fever During Infection With Low, Moderate, And Highly Virulent Strains In Relation To The Onset Of Clinical Signs. Journal of Virological Methods. (179):108-115. 4. Krug, P.W., Larson, C.R., Eslami, A.C., Rodriguez, L.L. 2012. Disinfection Of Foot-And-Mouth Disease And African Swine Fever Viruses With Citric Acid And Sodium Hypochlorite On Birch Wood Carriers. Veterinary Microbiology. 156:96- 101. 5. Uddowla, S., Hollister, J., Pacheco, J.M., Rodriguez, L.L., Rieder, E.A. 2012. A Safe Foot-And-Mouth Disease Vaccine Platform With Two Negative Markers For Differentiating Infected From Vaccinated Animals (Diva). Journal of Virology. Nov; 86(21):11675-85.

DHS Publications in 2012 1. Brake, D.A., McIlhaney, M., Miller, T., Christianson, K., Keene, A., Lohnas, G., Purcell, C., Neilan, J., Schutta, C., Barrera, J., Burrage, T., Brough, D.E., Butman, B.T. 2012. Human Adenovirus-Vectored Foot-And-Mouth Disease Vaccines: Establishment Of A Vaccine Product Profile Through In Vitro Testing. Dev Biol (134):123-33. 2. Burrage, T.G. 2012. African Swine Fever Virus Infection in Ornithodoros Ticks. Virus Research. 2013 Apr; 173(1):131-9. doi: 10.1016/j.virusres.2012.10.010. Epub 2012 Oct 17

ARS Publications in 2012 1. Biswal, J.K., Sanyal, A., Rodriguez, L.L., Subramaniam, S., Arzt, J., Sharma, G.K., Hammond, J.M., Parida, S., Mohapatra, J.K., Mathapati, B.S., Dash, B.B., Ranjan, R., Rout, M., Venketaramanan, R., Misri, J., Krishna, L., Prasad, G., Pathak, K.M., Pattnaik, B. 2012. Foot-And-Mouth Disease: Global Status And Indian Perspective. Indian Journal of Animal Sciences. 82(2):109-131. 2. Borca, M.V., Pacheco Tobin, J., Holinka-Patterson, L.G., Hartwig, E.J., Carrillo, C., Garriga, D., Kramer, E., Rodriguez, L.L., Piccone, M.E. 2012. Role Of The Arg56 Within The Structural Protein Vp3 Of Foot-And-Mouth Disease Virus (Fmdv) 01 Campos In Virus Virulence. Virology. (422):37-45. 3. Brito, B.P., Perez, A.M., Jamal, S.M., Belsham, G.J., Pauszek, S.J., Ahmed, Z., Rodriguez, L.L. 2012. Foot-and-Mouth Disease Virus Serotype O Phylodynamics: Genetic Variability Associated with Epidemiological Factors in Pakistan. Transboundary and Emerging Diseases. Jul 29. 4. Brockmeier, S.L., Loving, C.L., Nelson, E.A., Miller, L.C., Nicholson, T.L., Register, K.B., Grubman, M.J., Brough, D.E., Kehrli, M.E. Jr. 2012. The Presence of

Page 46 of 237

Alpha Interferon at the Time of Infection Alters the Innate and Adaptive Immune Responses to Porcine Reproductive and Respiratory Syndrome Virus. Clinical and Vaccine Immunology. 19(4):508-14. 5. Dias, C.C., Moraes, M., Weiss, M., Diaz-San Segundo, F. C., Perez-Martin, E., Salazar, A., De Los Santos, T., Grubman, M. 2012. Novel Antiviral Therapeutics to Control Foot-and-Mouth Disease. Journal of Interferon & Cytokine Research. Oct;32(10):462-73. 6. Diaz-San Segundo, F.C., Weiss, M., Perez-Martin, E., Dias, C.C., Grubman, M.J., De Los Santos, T.B. 2012. Inoculation Of Swine With Foot-And-Mouth Disease Sap-Mutant Virus Induces Early Protection Against Disease. Journal Of Virology. (86.3):1316-1327. 7. Gladue, D.P., Holinka, L.G., Largo, E., Fernandez-Sainz, I., Carrillo, C., O'donnell, V., Baker-Branstetter, R., Lu, Z., Ambroggio, X., Risatti, G.R., Nieva, J.L., Borca, M.V.2012. Classical Swine Fever Virus p7 Protein Is a Viroporin Involved in Virulence in Swine. Journal Of Virology. (86.12):6778-91. 8. Gladue, D.P., O'Donnell, V., Baker-Branstetter, R., Holinka, L.G., Pacheco, J.M., Fernandez-Sainz, I., Lu, Z., Brocchi, E., Baxt, B., Piconne, M.E., Rodriguez, L., Borca, M.V. 2012. Foot and Mouth Disease Virus non-structural protein 2C interacts with Beclin1 modulating virus replication. Journal of Virology. Nov; 86(22):12080- 90. 9. Grubman, M., Diaz-San Segundo, F.C., Dias, C.C., Moraes, M., Perez-Martin, E., De Los Santos, T. 2012. Use of Replication-Defective Adenoviruses to Develop Vaccines and Biotherapeutics Against Foot-and-Mouth Disease. Future Virology. 7 (8): 767-778 10. Lawrence, P.J., Schafer, E.A., Rieder, A.E. 2012. The Nuclear Protein Sam68 Is Cleaved By The Fmdv 3c Protease Redistributing Sam68 To The Cytoplasm During Fmdv Infection Of Host Cells. Virology. 425:40-52. 11. Montiel, N., Smoliga, G., Arzt, J. 2012. Early Detection And Visualization Of Human Adenovirus Serotype 5-Viral Vectors Carrying Foot-And-Mouth Disease Virus Or Luciferase Transgenes In Cell Lines And Bovine Tissues. Vaccine. (30):1690-1701 12. Pandya, M., Pacheco, J.M., Bishop, E., Kenney, M. Milward, F., Doel T., Golde, Wt. 2012. An Alternate Delivery System Improves Vaccine Performance Against Foot- And- Mouth Disease Virus (Fmdv). Vaccine. 30(20):3106-11. 13. Pauszek, S.J., Rodriguez, L.L. 2012. Full-Length Genome Analysis Of Vesicular Stomatitis New Jersey Virus Strains Representing The Phylogenetic And Geographic Diversity Of The Virus. Arch Virol. Nov; 157(11):2247-51. 14. Perez-Martin, E., Weiss, M., Diaz-San Segundo, F.C., Pacheco Tobin, J., Arzt, J., Grubman, M.J., De Los Santos, T.B. 2012. Bovine Type III Interferon Significantly Delays And Reduces The Severity Of Foot-And-Mouth Disease In Cattle. Journal Of Virology. 4477-4487.

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15. Rai, D., Rieder, E. 2012. Homology Modeling and Analysis of Structure Predictions of the Bovine Rhinitis B Virus RNA Dependent RNA Polymerase (RdRp). International Journal of Molecular Sciences. (13): 8998-9013. 16. Rodriguez, L.L., Pauszek, S.J. 2012. Chapter 4: Genus Vesiculoviruses. Rhabdoviruses. Edited by: Dietzgen, R.G., Kuzmin, I.V., Published By: Caister Academic Press, Norfolk, UK.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: PIADC provides the only research and development and confirmatory diagnostic capability for specific high-consequence, contagious, foreign animal diseases of livestock, including foot-and-mouth disease, in the U.S. Technologies researched and developed are vaccines, antivirals and diagnostic methods.

(ii) Agents Microorganisms and/or Toxins:

• USDA Select Agents and Toxins • Other pathogens or toxins

(iii) Outdoor Studies: None

Page 48 of 237

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Air Force Research Laboratory (AFRL), Materials and Manufacturing Directorate

2. Where is it located (provide both address and geographical location)?

2914 Hobson Way Wright-Patterson Air Force Base, Ohio 45433

3. Floor area of laboratory areas by containment level:

BL2 60 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 60 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 9

(ii) Division of personnel:

Military 2

Civilian 7

(iii) Division of personnel by category:

Scientists 9

Engineers 0

Technicians 0

Administrative and support staff 0

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Biochemistry, Materials Science, Microbiology, Molecular Biology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

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Yes Number: 5

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - wholly

(vii) What are the funding levels for the following program areas:

Research $ 400,000 Development $ 0 Test and evaluation $ 0 Total $ 400,000

(viii) Briefly describe the publication policy of the facility:

Unlimited release, prefer peer-reviewed journals for research results.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Dickenson M.B., Lyon W., Gruner W.E., Mirau P.A., Slocik J.M., Naik R.R. (2012) Sporicidal/Bactericidal Textiles via Chlorination of Silk. ACS Appl. Mater. Interfaces, 4, 1724-32

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: To functionalize natural polymers like silk, cotton, and wool using simple halamine chemistry and to test their antimicrobial properties against non-pathogenic microbial simulants.

(ii) Agents Microorganisms and/or Toxins:

• Other pathogens or toxins

(iii) Outdoor Studies: None

Page 50 of 237

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Lothar Salomon Test Facility (LSTF)

2. Where is it located (provide both address and geographical location)?

2029 Burns Road Dugway, Utah 84022-5006

3. Floor area of laboratory areas by containment level:

BL2 744 (sqM) BL3 414 (sqM) BL4 0 (sqM) Total laboratory floor area 1158 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 57

(ii) Division of personnel:

Military 0

Civilian 57

(iii) Division of personnel by category:

Scientists 39

Engineers 1

Technicians 9

Administrative and support staff 8

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Aerobiology, Bacteriology, Biochemistry, Engineering, Immunology, Microbiology, Molecular Biology, Toxicology, Virology

(v) Are contractor staff working in the facility? If so, provide an approximate

Page 51 of 237

number.

Yes Number: 13

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - partly U.S. Department of Homeland Security (DHS) U.S. Department of Justice (DOJ)

(vii) What are the funding levels for the following program areas:

Research $ 120,000 Development $ 0 Test and evaluation $ 4,100,000 Total $ 4,220,000

(viii) Briefly describe the publication policy of the facility:

Professional scientists are encouraged to publish papers in peer-reviewed journals. All publications must obtain the necessary command permission before submission.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Mark K. Gunnell, Charity D. Lovelace, Benjamin A. Satterfield, Emily Moore, Kim L. O'Neill and Richard A. Robison. "A multiplex real-time PCR assay for the detection and differentiation of Francisella tularensis subspecies." Journal of Medical Microbiology. Vol 61, (2012). 1525-1531

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: Testing of battlefield detection and identification methods, protective equipment, and decontamination systems, to include interferent testing of biological detectors and to

develop/validate aerosol particle dispersion models to enhance countermeasure response.

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(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A and B Priority Pathogens

• Overlap Select Agents Including NIAID Category A and B Priority Pathogens

• Other pathogens or toxins Including non-Select Agent, NIAID Category A, B and C Priority Pathogens

(iii) Outdoor Studies: Yes - using simulants

Page 53 of 237

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Naval Medical Research Center (NMRC)

2. Where is it located (provide both address and geographical location)?

(**Relocated in 2012 per U.S. Base Realignment and Closure Law**) 8400 Research Plaza

Fort Detrick, Maryland 21702

3. Floor area of laboratory areas by containment level:

BL2 2000 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 2000 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 72

(ii) Division of personnel:

Military 13

Civilian 59

(iii) Division of personnel by category:

Scientists 20

Engineers 0

Technicians 44

Administrative and support staff 8

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Biochemistry, Computational Biology, Immunology, Microbiology, Molecular Biology

(v) Are contractor staff working in the facility? If so, provide an approximate

Page 54 of 237

number.

Yes Number: 54

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - wholly

(vii) What are the funding levels for the following program areas:

Research $ 4,100,100 Development $ 0 Test and evaluation $ 689,600 Total $ 4,789,700

(viii) Briefly describe the publication policy of the facility:

Professional scientists are encouraged to publish worthy papers in peer-reviewed journals. All publications must obtain the necessary command and public affairs permission before submission.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

1. Dragan AI, Albrecht MT, Pavlovic R, Keane-Myers AM, Geddes CD. Ultra-fast pg/ml Anthrax toxin (protective antigen) detection assay based on Microwave Accelerated Metal-Enhanced Flourescence. Anal Biochem. 2012 Jun 1; 425(1):54-61. Epub 2012 Mar 6. 2. Zwick ME, Joseph SJ, Didelot X, Chen PE, Bishop-Lilly KA, Stewart AC, Willner K, Nolan NME, Lentz S, Thomason MPK, Sozhamannan S, Mateczun AJ, Du L, Read TD. Genomic characterization of the Bacillus cereus sensu lato species: Backdrop to the evolution of Bacillus anthracis. Genome Res. 2012 Aug 22: 1512-1524. Epub 2012 May 29. 3. Albrecht MT, Livingston BD, Pesce JT, Bell JT, Bell MG, Hannaman D, Keane-Myers AM. Electroporation of a multi-valent DNA vaccine cocktail elicits a protective immune response against anthrax and plague. Vaccine. 2012Jul6; 30(32):4872-83. Epub 2012 May 23. 4. Albrecht MT, Eyles JE, Baillie LW, Keane-Myers AM. Immunogenicity and efficacy of an anthrax/plague DNA fusion vaccine in a mouse model. FEMS Immunol Med

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Microbiol. 2012 Aug; 65(3): 505-509. Epub 2012 May 21. 5. Gebhart D, William S, Bishop-Lilly KA, Govoni GR, Willner KM, Butani A, Read TD, Sozhamannan S, Martin D, Fortier L-C, Scholl D. Novel high molecular weight, R-type bacteriocins of Clostridium difficile. J Bacteriol. 2012, 194(22):6240. Epub 2012 Sep 14. 6. Henry M, Biswas B, Vincent L, Mokashi V, Schuch R, Bishop-Lilly KA, Sozhamannan S. Development of a high throughput assay for indirectly measuring phage growth using the OmniLog™ system. Bacteriophage. 2012 Jul/Aug/Sep; 2(3):159-167. 7. Rashid MH, Revazishvili T, Dean T, Butani A, Verratti K, Bishop-Lilly KA, Sozhamannan S, Sulakvelidze A, Rajanna C. A Yersinia pestis specific, lytic phage preparation significantly reduces viable Y.pestis on various hard surfaces experimentally contaminated with the bacterium. Bacteriophage. 2012 Jul/Aug/Sep; 2(3):168-177.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: The goal of the program is the development of rapid and deployable detection assays to protect deployed troops. In a continued effort to have better prophylaxis measures, we are studying the potential use of multi-agent vaccines capable of conferring protection against multiple infectious diseases at once.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A and B Priority Pathogens

• Overlap Select Agents Including NIAID Category A and B Priority Pathogens

(iii) Outdoor Studies: None

Page 56 of 237

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Naval Research Laboratory (NRL)

2. Where is it located (provide both address and geographical location)?

4555 Overlook Avenue, SW Washington, District of Columbia 20375

3. Floor area of laboratory areas by containment level:

BL2 2271 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 2271 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 43

(ii) Division of personnel:

Military 0

Civilian 43

(iii) Division of personnel by category:

Scientists 33

Engineers 4

Technicians 6

Administrative and support staff 0

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Biochemistry, Biology, Biophysics, Chemical Engineering, Chemistry, Electrical Engineering, Engineering, Immunology, Mechanical Engineering, Microbiology, Molecular Biology, Physics

Page 57 of 237

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 11

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - partly National Institutes of Health (NIH)

(vii) What are the funding levels for the following program areas:

Research $ 7,205,000 Development $ 3,379,000 Test and evaluation $ 0 Total $ 10,584,000

(viii) Briefly describe the publication policy of the facility:

Employees are encouraged to publish. Employees must follow appropriate U.S. DoD guidelines for publishing information related to biological defense efforts and have all publications approved by the appropriate command authority. Public release of unclassified technical information is subject to sponsor approval.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

1. M. P. Raphael, J. A. Christodoulides, S. P. Mulvaney, M. M. Miller, J. P. Long, J. M. Byers. 2012. A New Methodology for Quantitative LSPR Biosensing and Imaging. Anal. Chem. 84, 1367-1373. 2. E.H. Lock, M. Baraket, M. Laskoski, S.P. Mulvaney, W.K. Lee, P.E. Sheehan, D.R. Hines, J.T. Robinson, J. Tosado, M.S. Fuhrer, S.C. Hernandez, S.G. Walton. High- Quality Uniform Dry Transfer of Graphene to Polymers. 2012. Nano Lett, 12(1):102- 107. DOI: 10.1021/nl203058s 21. 3. Robinson, J.; Zalalutdniov, M.; Junkermeier, C.; Culbertson, J.; Reinecke, T.; Stine, R.; Sheehan, P.; Houston, B.; Snow, E.2012. Structural Transformations in Chemically Modified Graphene. Solid State Communications. 152(21):1990-1998. DOI: 10.1016/j.ssc.2012.04.051 4. Zalalutdviov, M.; Robinson, J.; Junkermeier, C.; Culbertson, J.; Reinecke, T.; Stine, R.;

Page 58 of 237

Sheehan, P.; Houston, B.; Snow, E. 2012. Engineering Graphene Mechanical Systems Nano Letters. 12(8):4212-4218. 5. Baraket, M.; Walton, S.; Stine, R.; Lee, W.; Robinson, J.; Sheehan, P. Aminated Graphene for DNA Attachment Produced via Plasma Functionalization Applied Physics Letters 2012, Volume 100, Issue 23, id. 233123 DOI: 10.1063/1.4711771 6. Stine, R.; Ciszek, J.; Barlow, D.; Lee, W.; Robinson, J.; Sheehan, P. 2012. High Density Amine-Terminated Monolayers Formed on Fluorinated CVD-Grown Graphene. Langmuir. 28, 7957-7961. 7. Alex V. Terray, Qin Lu, Greg E. Collins, Sean J. Hart, Single particle analysis using fluidic, optical and electrophoretic force balance in a microfluidic system, Lab Chip, 2012,12, 1128-1134 DOI: 10.1039/C2LC21017G 8. Braden C. Giordano, Dean S. Burgi, Sean J. Hart, Alex Terray, On-line Sample Pre- concentration in Microfluidic Devices: A Review, Analytica Chimica Acta, 2012. 718:11-24. doi: 10.1016/j.aca.2011.12.050. Epub 2012 Jan 2. 9. Fulmer, P.A.; Wynne, J.H. "Coatings Capable of Germinating and Neutralizing Bacillus anthracis Endospores". ACS Applied Materials and Interfaces, 2012, 4 (2), 738-743. 10. Anderson, G.P., Legler, P.M., Zabetakis, D., Goldman, E.R. 2012 Comparison of Immunoreactivity of Staphylococcal Enterotoxin B Mutants for Use as Toxin Surrogates. Analytical Chemistry. 84:5198-5203 11. Hu, X., Legler, P.M., Khavrutskii, I., Scorpio, A., Compton, J.R., Robertson, K.R., Friedlander, A.M., WallqvistA. Biochemsitry (2012) 51(6):1199-212. 12. Jasenka Verbarg, Kian Kamgar-Parsi, Adam R. Shields, Peter B. Howell, Jr. and Frances S. Ligler, Spinning magnetic trap for automated microfluidic assay systems, Lab on a Chip, 2012, 12, 1793 13. "Automated processing integrated with a microflow cytometer for pathogen detection in clinical matrices" J.P. Golden, J. Verbarg, P.B. Howell Jr., L.C. Shriver-Lake, F.S. Ligler, Biosensors and Bioelectronics, 40(1), 2012, 10-16. 14. Walper, S.A., Anderson, G.P., Brozozog Lee, P.A., Glaven, R.H., Liu, J.L., Bernstein, R.D., Zabetakis, D., Johnson, L., Czarnecki, J.M. and Goldman, E.R., 2012, Rugged single domain antibody detection elements for Bacillus anthracis spores and vegetative cells. PLoS ONE 7, e32801. 15. Walper, S.A., Lee, P.A.B., Goldman, E.R., Anderson, G.P. 2012 Comparison of Single Domain Antibody Immobilization Strategies Evaluated by Surface Plasmon Resonance. Journal of Immunological Methods. 1759(12)00349-3 16. Liu, J.L., Zabetakis, D., Acevedo-Vélez, G., Goldman, E.R., Anderson, G.P. 2012 Comparison of an antibody and its recombinant derivative for the detection of the small molecule explosive 2, 4, 6- Trinitrotoluene. Analytica Chimica Acta, 759:100-4. Epub 2012. 17. Liu, J.L., Zabetakis, D., Goldman, E.R., Anderson, G.P. 2012 Selection and evaluation of single domain antibodies towards MS2 phage and coat protein. Molecular Page 59 of 237

Immunology. 53:118-125. 18. Anderson, G.P., Legler, P.M., Zabetakis, D., Goldman, E.R. 2012 Comparison of Immunoreactivity of Staphylococcal Enterotoxin B Mutants for Use as Toxin Surrogates. Analytical Chemistry. 84:5198-5203. 19. Glaven, R.H., Anderson, G.P., Zabetakis, D., Liu, J.L., Long, N.C., Goldman, E.R. 2012 Linking Single Domain Antibodies that Recognize Different Epitopes on the Same Target. Biosensors, 2:43-56 20. Biosensing with a Graphene-Based FET," C. R. Tamanaha, R. Stine, J. T. Robinson, M. Baraket, S. P. Mulvaney, S. G. Walton, P. E. Sheehan. 2012 NRL Review, NRL/O/6170-12-0077, in press.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: The objectives are to develop and test reliable systems for the detection of biological warfare agents in order to provide early warning and contamination avoidance information.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category B Priority Pathogens

• Other pathogens or toxins Including non-Select Agent, NIAID Category B Priority Pathogens

(iii) Outdoor Studies: None

Page 60 of 237

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Naval Surface Warfare Center-Dahlgren Division Chemical, Biological, Radiological (CBR) Defense Laboratory

2. Where is it located (provide both address and geographical location)?

6149 Welsh Road Dahlgren, Virginia 22448-5162

3. Floor area of laboratory areas by containment level:

BL2 190 (sqM) BL3 26 (sqM) BL4 0 (sqM) Total laboratory floor area 216 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 173

(ii) Division of personnel:

Military 0

Civilian 173

(iii) Division of personnel by category:

Scientists 60

Engineers 50

Technicians 16

Administrative and support staff 47

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Aerospace Engineering, Biology, Chemical Engineering, Chemistry, Computer Engineering, Computer Science, Electronic Engineering, General Engineering, Industrial Engineering, Mathematics, Mechanical Engineering, Microbiology, Molecular Biology, Operations Research Analysis, Physical Science, Physics, Software Engineering, Toxicology

Page 61 of 237

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 29

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - partly Private Sector Companies Internal (Laboratory Directed Research and Development, LDRD) Other Governmental Agencies

(vii) What are the funding levels for the following program areas:

Research $ 2,187,000 Development $ 3,602,000 Test and evaluation $ 11,768,000 Total $ 17,557,000

(viii) Briefly describe the publication policy of the facility:

Employees are encouraged to publish. Employees must follow appropriate U.S. DoD guidelines for publishing information related to biological defense efforts and have all publications approved. Public release of unclassified technical information is subject to sponsor approval.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

1. Buhr, T. et al. Test method development to evaluate hot, humid air decontamination of materials contaminated with Bacillus anthracis ∆Sterne and B. thuringiensis Al Hakam spores. Journal of Applied Microbiology November 2012. 113(5):1037-1051. 2. Buhr, T. et al. “Biological Decontamination.” Handbook of Chemical and Biological Warfare Agent Decontamination 2012: 245-279. 3. Cogley, K. HVAC Security Emergencies: No Terrorist Required. Engineered Systems July 2012: 26-31. 4. Gutting, B. Achieving consistent multiple day low-dose Bacillus anthracis spore inhalation exposures in the rabbit model. Frontiers in Cellular and Infection Microbiology 13 June 2012. 2:71. doi: 10.3389/fcimb.2012.00071

Page 62 of 237

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: Efforts at this defense laboratory are focused on biological detection systems, collective and individual protection systems, hazard mitigation technologies, risk assessment tools and consequence management planning.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A and B Priority Pathogens

• Overlap Select Agents Including NIAID Category A Priority Pathogens

• Other pathogens or toxins

(iii) Outdoor Studies: None

Page 63 of 237

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Tyndall Air Force Base (AFB) -- 1

2. Where is it located (provide both address and geographical location)?

3000 Research Road Tyndall AFB, Florida 32403

3. Floor area of laboratory areas by containment level:

BL2 55 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 55 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 6

(ii) Division of personnel:

Military 1

Civilian 5

(iii) Division of personnel by category:

Scientists 4

Engineers 0

Technicians 1

Administrative and support staff 1

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Microbiology

(v) Are contractor staff working in the facility? If so, provide an approximate

Page 64 of 237

number.

Yes Number: 5

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Health and Human Services (HHS)

(vii) What are the funding levels for the following program areas:

Research $ 800,000 Development $ 0 Test and evaluation $ 150,000 Total $ 950,000

(viii) Briefly describe the publication policy of the facility:

Unlimited release, prefer peer-reviewed journals for research results; limit to U.S. Government for test and evaluation and proprietary data.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

1. McDonald RS, AR Sambol, BK Heimbach, TL Brown, SH Hinrichs, JD Wander, Proportional mouse model for aerosol infection by Influenza, Journal of Applied Microbiology, 2012; 113:767-778. 2. Stone BR, BK Heimbach, C-Y Wu2, JD Wander, Design, construction and validation of a nose-only inhalation exposure system to measure infectivity of filtered bioaerosols in mice, Journal of Applied Microbiology, 2012; 113:757-766. 3. Lore MB, BK Heimbach, TL Brown, JD Wander, SH Himrichs, Effectiveness of Three Decontamination Treatments against Influenza Virus Applied to Filterin Faceplate Respirators. Annals of Occupational Hygiene, 2012; 56 (1):92-101.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives:

Page 65 of 237

The facility houses and supports a bioaerosol test chamber in which aerosols containing biological simulants are used for defensive purposes to characterize the size distribution of bioaerosol challenges as needed.

(ii) Agents Microorganisms and/or Toxins:

• Other pathogens or toxins Including non-Select Agent, NIAID Category B and C Priority Pathogens

(iii) Outdoor Studies: None

Page 66 of 237

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Tyndall Air Force Base (AFB) -- 2

2. Where is it located (provide both address and geographical location)?

139 Barnes Drive Tyndall AFB, Florida 32403

3. Floor area of laboratory areas by containment level:

BL2 53 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 53 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 8

(ii) Division of personnel:

Military 1

Civilian 7

(iii) Division of personnel by category:

Scientists 5

Engineers 1

Technicians 1

Administrative and support staff 1

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Chemistry, Environmental Engineering, Physics

(v) Are contractor staff working in the facility? If so, provide an approximate

Page 67 of 237

number.

Yes Number: 5

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - wholly

(vii) What are the funding levels for the following program areas:

Research $ 150,000 Development $ 280,000 Test and evaluation $ 0 Total $ 430,000

(viii)Briefly describe the publication policy of the facility:

Unlimited release, prefer peer-reviewed journals for research results; limit to U.S. Government for test and evaluation and proprietary data

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

None

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: This facility supports the preparation and characterization of novel chemicals expected to exhibit antimicrobial properties. Materials are tested only against Biosafety Level 1 microorganisms at this facility. It also supports research into degradation products formed by exposure of samples of reactive materials to simulant chemical threat agents.

(ii) Agents Microorganisms and/or Toxins:

• Other pathogens or toxins

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(iii) Outdoor Studies: None

Page 69 of 237

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

U.S. Army Edgewood Chemical and Biological Center

2. Where is it located (provide both address and geographical location)?

5183 Blackhawk Road Aberdeen Proving Ground, Maryland 21010-5424

3. Floor area of laboratory areas by containment level:

BL2 532 (sqM) BL3 177 (sqM) BL4 0 (sqM) Total laboratory floor area 709 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 274

(ii) Division of personnel:

Military 0

Civilian 274

(iii) Division of personnel by category:

Scientists 188

Engineers 35

Technicians 21

Administrative and support staff 30

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Aerobiology, Aerospace Engineering, Biochemistry, Biology, Biomedical Engineering, Biotechnology, Chemical Engineering, Chemistry, Computer Engineering, Electronic Engineering, General Engineering, Immunology, Mathematics, Mechanical Engineering,

Page 70 of 237

Microbiology, Molecular Biology, Operations Research Analysis, Physical Science, Physics, Physiology, Statistics, Toxicology, Toxinology, Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 137

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - wholly

(vii) What are the funding levels for the following program areas:

Research $ 1,427,000 Development $ 19,871,000 Test and evaluation $ 0 Total $ 21,298,000

(viii) Briefly describe the publication policy of the facility:

Publications are prepared in accordance with Army regulations. Scientists are encouraged to publish their results in peer-reviewed scientific literature as well as present their work at national and international professional meetings.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

1. Buckley, P., Rivers, B., Katoski, S., Kim, M.H., Kragl, F.J., Broomall, S., Krepps, M., Skowronski, E.W., Rosenzweig C.N., Paikoff, S., Emanuel, P., Gibbons, H.S. Barcodes for Improved Environmental Tracking of an Anthrax Simulant. Appl. Environ. Microbiol. Accepted for Publication 2012. 2. Chen B, Shah SS, Shin Y, Lei C, Liu J. In vitro release of organophosphorus acid anhydrolase from functionalized mesoporous silica against nerve agents. Anal Biochem. 2012 Feb 15; 421(2):477-81. 3. Emanuel, P., Buckley, P., Sutton, T., Edmonds, J., Bailey, A., Rivers, B., Kim, M., Ginley, W., Keiser, C., Doherty, R., Kragl, F.J., Narayanan, F., Katoski, S., Paikoff, S., Leppert, S., Strawbridge, J., VanReenen, D., Biberos, S., Moore, D., Philips, D., Mingioni, L., Melles, O., Ondercin, D., Hirsh, E., Bieschke, K., Harris, C., Omberg, K.,

Page 71 of 237

Rastogi, V., Van Cuyk, S., and Gibbons, H. Detection and tracking of a novel genetically-tagged biological simulant in the environment. Appl. Environ. Microbiol. Accepted for Publication, 2012. 4. Gibbons, H., et al. Comparative Genomics of 2009 seasonal plague (Yersinia pestis) in New Mexico. PLoS ONE, 2012, 7(2):e31604. 5. Hughes, R.A., Miklos, A.E., and Ellington, A.D. (2012). Enrichment of Error-Free Synthetic DNA Sequences by CEL I Nuclease. In Current Protocols in Molecular Biology, (John Wiley &Sons, Inc.) 6. Miklos AE; Kluwe C; Der BS; Pai S; Sircar A; Hughes RA; Berrondo M; Xu J; Codrea V; Buckley PE; Calm AM; Welsh HS; Warner CR; Zacharko MA; Carney JP; Gray JJ; Georgiou G; Kuhlman B; and Ellington A. Structure-based Design of Supercharged, Highly Thermoresistant Antibodies. Chem Biol. 19(4):449-455, 2012. 7. Miklos, A.E., Hughes, R.A., and Ellington, A.D. (2012). Design and Assembly of Large Synthetic DNA Constructs. In Current Protocols in Molecular Biology, (John Wiley & Sons, Inc.) 8. Patel, K., V.D Dixit, J.H. Lee, J.W. Kim, E.M. Schaffer, D. Nguyen and D.D. Taub Identification of Ghrelin Receptor Blocker, D-[Lys3] GHRP-6 as a CXCR4 Receptor Antagonist. Int. J. Biol. Sci.; 8(1):108-117, 2012. 9. Patel, K., V.D Dixit, J.H. Lee, J.W. Kim, E.M. Schaffer, D. Nguyen and D.D. Taub The GHS-R Blocker D-[Lys3] GHRP-6 Serves as CCR5 Chemokine Receptor Antagonist. Int. J. Med. Sci.;9(1):51-58, 2012. 10. Romero, P.A., Stone, E., Lamb, C., Chantranupong, L., Krause, A., Miklos, A.E., Hughes, R.A., Fechtel, B., Ellington, A.D., Arnold, F.H., et al. SCHEMA-Designed Variants of Human Arginase I and II Reveal Sequence Elements Important to Stability and Catalysis. ACS Synth. Biol.; 1:221-228, 2012. 11. Sagripanti JL, Voss L, Marschall HJ, David Lytle C. Inactivation of Vaccinia Virus by Natural Sunlight and by Artificial UVB Radiation. Photochem Photobiol. 2012 Jul 21. doi: 10.1111/j.1751-1097.2012.01207.x. [Epub ahead of print]

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: Development of non-medical defensive material against biological agents to include: research, development, and engineering for methods of rapid detection, identification, decontamination, and physical protection from biological threat agents.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins

Page 72 of 237

Including NIAID Category A, B and C Priority Pathogens

• Overlap Select Agents Including NIAID Category A and B Priority Pathogens

• Other pathogens or toxins Including non-Select Agent, NIAID Category B Priority Pathogens

(iii) Outdoor Studies: None

Page 73 of 237

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

U.S. Army Medical Research Institute of Chemical Defense (USAMRICD)

2. Where is it located (provide both address and geographical location)?

3100 Ricketts Point Road Aberdeen Proving Ground, Maryland 21010-5400

3. Floor area of laboratory areas by containment level:

BL2 300 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 300 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 9

(ii) Division of personnel:

Military 0

Civilian 9

(iii) Division of personnel by category:

Scientists 4

Engineers 0

Technicians 5

Administrative and support staff 0

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Biochemistry, Biology, Molecular Biology, Pharmacology, Physiology

(v) Are contractor staff working in the facility? If so, provide an approximate

Page 74 of 237

number.

Yes Number: 5

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - wholly

(vii) What are the funding levels for the following program areas:

Research $ 940,000 Development $ 0 Test and evaluation $ 0 Total $ 940,000

(viii) Briefly describe the publication policy of the facility:

Publications are prepared and published in accordance with Army regulations.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

1. Adler, Michael, Deshpande, Sharad S., Apland, James P., Murray, B., Borrell, Andrew. Reversal of BoNT/A-mediated inhibition of muscle paralysis by 3,4-diaminopyridine and roscovitine in mouse phrenic nerve-hemidiaphragm preparations. Neurochem International 61(6):866-873, 2012. (2012 Jul 25 - Epub ahead of print) 3. 2. Hubbard KS, Gut IM, Lyman ME, Tuznik KM, Mesngon MT, McNutt PM. High yield derivation of enriched glutamatergic neurons from suspension-cultured mouse ESCs for neurotoxicology research. BMC Neuroscience 2012 Oct 24; 13:127.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: The Institute's mission involves research on medical defenses against neurotoxins.

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(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A Priority Pathogens

(iii) Outdoor Studies: None

Page 76 of 237

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID)

2. Where is it located (provide both address and geographical location)?

1425 Porter Street Fort Detrick

Frederick, Maryland 21702-5011

3. Floor area of laboratory areas by containment level:

BL2 26026 (sqM) BL3 3139 (sqM) BL4 1186 (sqM) Total laboratory floor area 30351 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 831

(ii) Division of personnel:

Military 201

Civilian 630

(iii) Division of personnel by category:

Scientists 263

Engineers 3

Technicians 293

Administrative and support staff 272

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Aerobiology, Biochemistry, Biology, Chemistry, Clinical Immunology, Entomology, Genetics, Immunology, Infectious Disease, Internal Medicine, Microbiology, Molecular

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Biology, Preventive Medicine, Toxicology, Veterinary Medicine, Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 292

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - wholly

(vii) What are the funding levels for the following program areas:

Research $ 26,043,314 Development $ 39,342,622 Test and evaluation $ 854,892 Total $ 66,240,828

(viii) Briefly describe the publication policy of the facility:

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

1. Akhvlediani T, Chitadze N, Laws TR, Makharadze M, Chubinidze M, Tsanava S, Commander NJ, Perkins SD, Dyson EH, Rivard RG, Hepburn MJ, Simpson AJH, Imnadze P, Trapaidze N. Comparison of total antibody and interferon-gammaT-cell responses in patients following infection with brucellosis in Georgia. Journal of Infection and Public Health 2012 Oct, 5(5): 321 - 331 2. Arrigo NC, Briese T, Calisher CH, Drebot MA, Fljelle B, LeDuc JW, Powers AM, Repik PM, Roehrig JT, Schmaljohn CS, Tesh RB, Weaver SC. Recommendations for Publication of Viral Genetic Data and Sample Access for Novel Viruses and Strains. American Journal of Tropical Medicine and Hygiene 2012 Feb, 86(2): 189-191 3. Bale S, Dias JM, Fusco ML, Hashiguchi T, Wong AC, Liu T, Keuhne AI, Li S, Woods VL Jr, Chandran K, Dye JM, Saphire EO. Structural basis for differential neutralization of ebolaviruses. Viruses. 2012 Apr, 4(4): 447-70

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4. Boudreau EF, Josleyn M, Ullman D, Fisher D, Dalrymple L, Sellers-Myers K, Loudon P, Rusnak J, Rivard R, Schmaljohn C, Hooper JW. A Phase 1 clinical trial of Hantaan virus and Puumala virus M-segment DNA vaccines for hemorrhagic fever with renal syndrome. Vaccine 2012 Mar 2; 30(11): 1951-1958 5. Bozue J, Cote CK, Webster W, Bassett A, Tobery S, Little S, Swietnicki W. A Yersinia pestis YscN ATPase mutant functions as a live attenuated vaccine against bubonic plague in mice. FEMS Microbiology Letters 2012 July, 332(2): 113-121 6. Brocato R, Josleyn M, Ballantyne J, Vial P, Hooper JW. DNA vaccine-generated duck polyclonal antibodies as a postexposure prophylactic to prevent hantavirus pulmonary syndrome (HPS). PLoS One 2012, 7(4): e35996 7. Byers DM, Gorbet JC, Irwin LN. Disialogangliosides and TNF-alpha alter gene expression for cytokines and chemokines in primary brain cell cultures. Neurochemical Research 2012 Jan, 37(1): 214-222 8. Cardellina JH, Roxas-Duncan VI, Montgomery V, Eccard V, Campbell Y, Hu X, Khavrutskii I, Tawa GJ, Wallqvist A, Gloer JB, Phatak NL, Hoeller U, Soman AG, Joshi BK, Hein SM, Wicklow DT, Smith LA. Fungal bis-Naphthopyrones as Inhibitors of Botulinum Neurotoxin Serotype A. ACS Medicinal Chemistry Letters 2012 May, 3(5): 387-391 9. Chabot DJ, Joyce J, Caulfield M, Cook J, Hepler R, Wang S, Vietri NJ, Ruthel G, Shoop W, Pitt L, Leffel E, Ribot W, Friedlander AM. Efficacy of a capsule conjugate vaccine against inhalational anthrax in rabbits and monkeys. Vaccine 2012 Jan 20, 30(5): 846-52 10. Chaudhury S, Olson MA, Tawa G, Wallqvist A, Lee MS. Efficient Conformational Sampling in Explicit Solvent Using a Hybrid Replica Exchange Molecular Dynamics Method. Journal of Chemical Theory and Computation 2012 Feb, 8(2): 677-687 11. Cisney ED, Fernandez S, Hall SI, Krietz GA, Ulrich RG. Examining the role of nasopharyngeal-associated lymphoreticular tissue (NALT) in mouse responses to vaccines. Journal of Visualized Experiments 2012 Aug 1, (66): 3960 12. Cote CK, Kaatz L, Reinhardt J, Bozue J, Tobery SA, Bassett AD, Sanz P, Darnell SC, Alem F, O'Brien AD, Welkos SL. Characterization of a multi-component anthrax vaccine designed to target the initial stages of infection as well as toxaemia. Journal of Medical Microbiology 2012 Oct, 61(10): 1380-92 13. Dabisch P, Yeager J, Kline J, Klinedinst K, Welsch A, Pitt ML. Comparison of the efficiency of sampling devices for aerosolized Burkholderia pseudomallei Inhalation. Toxicology 2012 Apr, 24(5): 247-254 14. Del Favero G, Florio C, Codan B, Sosa S, Poli M, Sbaizero O, Molgó J, Tubaro A, Lorenzon P. The stretch-activated channel blocker Gd 3+ reduces palytoxin toxicity in primary cultures of skeletal muscle cells. Chemical Research in Toxicology 2012 Sept 17, 25(9): 1912-1920 15. Do Y, Didierlaurent AM, Ryu S, Koh H, Park CG, Park S, Perlin DS, Powell BS,

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Steinman RM. Induction of pulmonary mucosal immune responses with a protein vaccine targeted to the DEC-205/CD205 receptor. Vaccine. 2012 Oct 5, 30(45): 6359- 67 16. Dower K, Filone CM, Hodges EN, Bjornson ZB, Rubins KH, Brown LE, Schaus S, Hensley LE, Connor JH. Identification of a Pyridopyrimidinone Inhibitor of Orthopoxviruses from a Diversity-Oriented Synthesis Library. Journal of Virology 2012 Mar, 86(5): 2632-2640 17. Dupuy LC, Reed DS. Nonhuman primate models of encephalitic alphavirus infection: historical review and future perspectives. Current Opinion in Virology 2012 June 2012, 2(3): 363-7 18. Dye JM, Herbert AS, Kuehne AI, Barth JF, Muhammad MA, Zak SE, Ortiz RA, Prugar LI, Pratt WD. Postexposure antibody prophylaxis protects nonhuman primates from filovirus disease. Proceedings of the National Academy of Sciences of the USA 2012 Mar 27, 109(13): 5034-5039 19. Edupuganti OP, Ovsepian SV, Wang J, Zurawski TH, Schmidt JJ, Smith L, Lawrence GW, Dolly JO. Targeted delivery into motor nerve terminals of inhibitors for SNARE- cleaving proteases via liposomes coupled to an atoxic botulinum neurotoxin. FEBS Journal 2012 July, 279(14): 2555-2567 20. Eppinger M, Radnedge L, Andersen G, Vietri N, Severson G, Mou S, Ravel J, Worsham PL. Novel Plasmids and Resistance Phenotypes in Yersinia pestis: Unique Plasmid Inventory of Strain Java 9 Mediates High Levels of Arsenic Resistance. PLoS One 2012, 7(3): e32911 21. Erwin-Cohen RA, Porter AI, Pittman PR, Rossi CA, DaSilva L. Host responses to live- attenuated Venezuelan equine encephalitis virus (TC-83): Comparison of naïve, vaccine responder and nonresponder to TC-83 challenge in human peripheral blood mononuclear cells. Human Vaccines and Immunotherapeutics 2012 Aug, 8(8): 1053- 1065 22. Fenimore PW, Muhammad MA, Fischer WM, Foley BT, Bakken RR, Thurmond JR, Yusim K, Yoon H, Parker M, Hart MK, Dye JM, Korber B, Kuiken C. Designing and Testing Broadly-Protective Filoviral Vaccines Optimized for Cytotoxic T-Lymphocyte Epitope Coverage. PLoS One 2012, 7(10): e44769 23. Fisher NA, Ribot WJ, Applefeld W, Deshazer D. The Madagascar hissing cockroach as a novel surrogate host for Burkholderia pseudomallei, B. mallei and B. thailandensis. BMC Microbiology 2012 June 22, 12: 117 24. Forsberg LS Abshire TG Friedlander A Quinn CP Kannenberg EL Carlson RW. Localization and structural analysis of a conserved pyruvylated epitope in Bacillus anthracis secondary cell wall polysaccharides and characterization of the galactose- deficient wall polysaccharide from avirulent B-anthracis CDC 684. Glycobiology 2012 Aug, 22(8): 1103-1117 25. Friedrich BM, Trefry JC, Biggins JE, Hensley LE, Honko AN, Smith DR, Olinger GG. Potential vaccines and post-exposure treatments for filovirus infections. Viruses 2012

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Sept, 4(9): 1619-1650 26. Fuller T, Thomassen HA, Mulembakani PM, Johnston SC, Lloyd-Smith JO, Kisalu NK, Lutete TK, Blumberg S, Fair JN, Wolfe ND, Shongo RL, Formenty P, Meyer H, Wright LL, Muyembe JJ, Buermann W, Saatchi SS, Okitolonda E, Hensley L, Smith TB, Rimoin AW. Using Remote Sensing to Map the Risk of Human Monkeypox Virus in the Congo Basin. Ecohealth 2012 Mar 5, 8(1):14-25 27. Gaidamakova EK, Myles IA, McDaniel DP, Fowler CJ, Valdez PA, Naik S, Gayen M, Gupta P, Sharma A, Glass PJ, Maheshwari RK, Datta SK, Daly MJ. Preserving Immunogenicity of Lethally Irradiated Viral and Bacterial Vaccine Epitopes Using a Radio-Protective Mn2+-Peptide Complex from Deinococcus. Cell Host & Microbe 2012 July 19, 12(1): 117-24 28. Golden JW, Josleyn M, Mucker EM, Hung C-F, Loudon PT, Wu TC, Hooper JW. Side- by-side comparison of gene-based smallpox vaccine with MVA in nonhuman primates. PLoS One 2012 7(7): e42353 29. Hale ML, Cai S, Ahmed SA. Medical applications of clostridia and clostridial toxins. Journal of Toxicology 2012, 2012: 678963 30. Hart MK, Saviolakis GA, Welkos SL, House RV. Advanced Development of the rF1V and rBV A/B Vaccines: Progress and Challenges. Advances in Preventive Medicine 2012: 731604 31. Higa MM, Petersen J, Hooper J, Doms RW. Efficient production of Hantaan and Puumala pseudovirions for viral tropism and neutralization studies. Virology 2012 Feb 20 423(2): 134-142 32. Hines HB. Microbial proteomics using mass spectrometry. Methods in Molecular Biology 2012, 881: 159-186 33. Hoke CH, Pace-Templeton J, Pittman P, Malinoski FJ, Gibbs P, Ulderich T, Mathers M, Fogtman B, Glass P, Vaughn DW. US Military contributions to the global response to pandemic Chikungunya. Vaccine 2012 Oct 19, 30(47): 6713 - 6720 34. Hu X, Legler PM, Khavrutskii I, Scorpio A, Compton JR, Robertson KL, Friedlander AM, Wallqvist A. Probing the Donor and Acceptor Substrate Specificity of the gamma- Glutamyl Transpeptidase. Biochemistry 2012 Feb 14 51(6): 1199-1212 35. Jing X, Robinson HR, Heffron JD, Popham DL, Schubot FD. The catalytic domain of the germination-specific lytic transglycosylase SleB from Bacillus anthracis displays a unique active site topology. Proteins: Structure, Function and Bioinformatics 2012 Oct: 80(10): 2469 - 2475 36. Johnston SC, Lin KL, Connor JH, Ruthel G, Goff A, Hensley LE. In vitro inhibition of monkeypox virus production and spread by Interferon-beta. Virology Journal 2012 Jan 6, 9: 5 37. Kalb SR, Baudys J, Rees JC, Smith TJ, Smith LA, Helma CH, Hill K, Kull S, Kirchner S, Dorner MB, Dorner BG, Pirkle JL, Barr JR. De novo subtype and strain identification of botulinum neurotoxin type B through toxin proteomics. Analytical &

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Bioanalytical Chemistry 2012 Apr 403(1): 215-26 38. Kalb SR, Baudys J, Webb RP, Wright P, Smith TJ, Smith LA, Fernandez R, Raphael BH , Maslanka SE, Pirkle JL, Barr JR. Discovery of a novel enzymatic cleavage site for botulinum neurotoxin F5. FEBS Letters 2012 Jan 20 586(2): 109-115 39. Kissner TL, Ruthel G, Alam S, Mann E, Ajami D, Rebek M, Larkin E, Fernandez S, Ulrich RG, Ping S, Waugh DS, Rebek J, Saikh KU. Therapeutic inhibition of proinflammatory signaling and toxicity to staphylococcal enterotoxin B by a synthetic dimeric BB-loop mimetic of MyD88. PLoS One 2012 7(7): e40773 40. Kota KP, Benko JG, Mudhasani R, Retterer C, Tran JP, Bavari S, Panchal RG. High content image based analysis identifies cell cycle inhibitors as regulators of ebola virus infection. Viruses 2012 Sept 25, 4(10): 1865 - 1877 41. Krakauer T, Buckley M. Intranasal rapamycin rescues mice from staphylococcal enterotoxin B-induced shock. Toxins 2012 Sept, 4(9): 718-728 42. Kugelman JR, Lee MS, Rossi CA, McCarthy SE, Radoshitzky SR, Dye JM, Hensley LE, Honko A, Kuhn JH, Jahrling PB, Warren TK, Whitehouse CA, Bavari S, Palacios G. Ebola Virus Genome Plasticity as a Marker of Its Passaging History: A Comparison of In Vitro Passaging to Non-Human Primate Infection. PLoS One, 7(11): e50316 43. Kumar G, Kumaran D, Ahmed SA, Swaminathan S. Peptide inhibitors of botulinum neurotoxin serotype A: Design inhibition cocrystal structures structure-activity relationship and pharmacophore modeling. Acta Crystallographica Section D: Biological Crystallography 2012 May, 68(5): 511-520 44. Lebeda FJ, Dembek ZF, Adler M. Kinetic and reaction pathway analysis in the application of botulinum toxin a for wound healing. Journal of Toxicology 2012, 2012: 159726 45. Lindsey CY, Powell BS, Bolt CR, Brown JE, Adamovicz JJ. Validation of quantitative ELISAs for measuring anti-yersinia pestis F1 and V antibody concentrations in nonhuman primate sera. Journal of Immunoassay & Immunochemistry 2012 Jan, 33 (1): 91-113 46. Louie A, VanScoy BD, Brown DL, Kulawy RW, Heine HS, Drusano GL. Impact of spores on the comparative efficacies of five antibiotics for treatment of Bacillus anthracis in an in vitro hollow fiber pharmacodynamic model. Antimicrobial Agents and Chemotherapy 2012 Mar 56(3): 1229-1239 47. Louie A, VanScoy BD, Heine HS, Liu W, Abshire T, Holman K, Kulawy R, Brown DL, Drusano GL. Differential effects of linezolid and ciprofloxacin on toxin production by Bacillus anthracis in an in Vitro pharmacodynamic system. Antimicrobial Agents and Chemotherapy 2012 Mar 56(1): 513-517 48. McLain DE, Lewis BS, Chapman JL, Wannemacher RW, Lindsey CY, Smith LA. Protective Effect of Two Recombinant Ricin Subunit Vaccines in the New Zealand White Rabbit Subjected to a Lethal Aerosolized Ricin Challenge: Survival Immunological Response and Histopathological Findings. Toxicological Sciences 2012

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Mar 126(1): 72-83 49. Miller EH, Obernosterer G, Raaben M, Herbert AS, Deffieu MS, Krishnan A, Ndungo E, Sandesara RG, Carette JE, Kuehne A,I Ruthel G, Pfeffer SR, Dye JM, Whelan SP, Brummelkamp TR, Chandran K. Ebola virus entry requires the host-programmed recognition of an intracellular receptor. EMBO Journal 2012 Apr 18 31(8): 1947-1960 50. Mire CE, Miller AD, Carville A, Westmoreland SV, Geisbert JB, Mansfield KG, Feldmann H, Hensley LE, Geisbert TW. Recombinant Vesicular Stomatitis Virus Vaccine Vectors Expressing Filovirus Glycoproteins Lack Neurovirulence in Nonhuman Primates. PLoS Neglected Tropical Diseases 2012 Mar 6(3): e1567 51. Misasi J, Chandran K, Yang JY, Considine B, Filone CM, Cote M, Sullivan N, Fabozzi G, Hensley L, Cunningham J. Filoviruses Require Endosomal Cysteine Proteases for Entry but Exhibit Distinct Protease Preferences. Journal of Virology 2012 Mar 86(6): 3284-3292 52. Mizanur RM, Gorbet J, Swaminathan S, Ashraf Ahmed S. Inhibition of catalytic activities of botulinum neurotoxin light chains of serotypes A B and E by acetate sulfate and calcium. International Journal of Biochemistry and Molecular Biology 2012 3 (3): 313 - 321 53. Mou S, Cote CK, Worsham PL. Cytotoxic necrotizing factor is an effective immunogen in a Yersinia pseudotuberculosis aerosol mouse model. Advances in Experimental Medicine and Biology 2012, 954: 179-181 54. Mukherjee J, Tremblay JM, Leysath CE, Ofori K, Baldwin K, Feng XC, Bedenice D, Webb RP, Wright PM, Smith LA, Tzipori S, Shoemaker CB. A Novel Strategy for Development of Recombinant Antitoxin Therapeutics Tested in a Mouse Botulism Model. PLoS One 2012 7(1): e29941 55. Narayanan A, Kehn-Hall K, Senina S, Lundberg L, Van Duyne R, Guendel I, Das R, Baer A, Bethel L, Turell M, Hartman AL, Das B, Bailey C, Kashanchi F. Curcumin inhibits rift valley fever virus replication in human cells. Journal of Biological Chemistry 2012 Sept 28, 287(40): 33198 - 33214 56. Ngundi MM, Meade BD, Little SF, Quinn CP, Corbett CR, Brady RA, Burns DL. Analysis of defined combinations of monoclonal antibodies in anthrax toxin neutralization assays and their synergistic action. Clinical and Vaccine Immunology 2012 May 19(5): 731-739 57. Nygaard RM, Golden JW, Schiff LA. Impact of host proteases on reovirus infection in the respiratory tract. Journal of Virology 2012 Jan 86(2): 1238-1243 58. Olal D, Kuehne AI, Bale S, Halfmann P, Hashiguchi T, Fusco ML, Lee JE, King LB, Kawaoka Y, Dye JM, Saphire EO. Structure of an Antibody in Complex with Its Mucin Domain Linear Epitope That Is Protective against Ebola. Virus Journal of Virology 2012 Mar 86(5): 2809-2816 59. Olinger GG, Pettitt J, Kim D, Working C, Bohorov O, Bratcher B, Hiatt E, Hume SD, Johnson AK, Morton J, Pauly M, Whaley KJ, Lear CM, Biggins JE, Scully C, Hensley

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L, Zeitlin L. Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques. Proceedings of the National Academy of Sciences of the USA. 2012 Oct 30, 109(44): 18030-18035 60. Opsenica I, Filipovic V, Nuss JE, Gomba LM, Opsenica D, Burnett JC, Gussio R, Solaja BA, Bavari S. The synthesis of 25-bis(4-amidinophenyl)thiophene derivatives providing submicromolar-range inhibition of the botulinum neurotoxin serotype A metalloprotease. European Journal of Medicinal Chemistry 2012 July 53: 374-379 61. Panchal RG, Geller BL, Mellbye B, Lane D, Iversen PL, Bavari S. Peptide Conjugated Phosphorodiamidate Morpholino Oligomers Increase Survival of Mice Challenged with Ames Bacillus anthracis. Nucleic Acid Therapeutics 2012 Oct, 22 (5):316-322 62. Panchal RG, Reid SP, Tran JP, Bergeron AA, Wells J, Kota KP, Aman J, Bavari S. Identification of an antioxidant small-molecule with broad-spectrum antiviral activity. Antiviral Research 2012 Jan 93(1): 23-9 63. Pegoraro G, Bavari S, Panchal RG. Shedding light on filovirus infection with high- content imaging. Viruses 2012 Aug, 4(8): 1354-71 64. Pelin M, Sosa S, Della Loggia R, Poli M, Tubaro A, Decorti G, Florio C. The cytotoxic effect of palytoxin on Caco-2 cells hinders their use for in vitro absorption studies. Food and Chemical Toxicology 2012 Feb: 50(2): 206-211 65. Powell BS, Lazarev AV, Carlson G, Ivanov AR, Rozak DA. Pressure cycling technology in systems biology. Methods in Molecular Biology 2012 881: 27-62 66. Radoshitzky SR, Kuhn JH, de Kok-Mercado F, Jahrling PB Bavari S. Drug discovery technologies and strategies for Machupo virus and other New World arenaviruses. Expert Opinion on Drug Discovery 2012 July 7(7): 613-32 67. Reed C, Steele KE, Honko A, Shamblin J, Hensley LE, Smith DR. Ultrastructural study of Rift Valley fever virus in the mouse model. Virology 2012 Sept 15 431(1-2): 58-70 68. Reid StP, Shurtleff AC, Bavari S. Emerging therapeutic options against filoviruses. Drugs of the Future 2012 May 37(5): 343-351 69. Reinbold-Wasson DD, Sardelis MR, Jones JW, Watts DM, Fernandez R, Carbajal F, Pecor JE, Calampa C, Klein TA, Turell MJ. Determinants of Anopheles Seasonal Distribution Patterns Across a Forest to Periurban Gradient near Iquitos Peru. American Journal of Tropical Medicine and Hygiene 2012 Mar 86(3): 459-463 70. Reisler RB, Gibbs PH, Danner DK, Boudreau EF. Immune interference in the setting of same-day administration of two similar inactivated alphavirus vaccines: Eastern equine and western equine encephalitis. Vaccine 2012 Nov 26, 30 (50): 7271 - 7277 71. Reisler RB, Smith LA. The need for continued development of ricin countermeasures. Advances in Preventive Medicine 2012; 2012: 149737 72. Ridnour LA, Barasch KM, Windhausen AN, Dorsey TH, Lizardo MM, Yfantis HG, Lee DH, Switzer CH, Cheng RYS, Heinecke JL, Brueggemann E, Hines HB, Khanna C, Glynn SA, Ambs S, Wink DA. Nitric Oxide Synthase and Breast Cancer: Role of

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TIMP-1 in NO-mediated Akt Activation. PLoS One 2012, 7(9): e44081 73. Romero R, Soto E, Berry SM, Hassan SS, Kusanovic JP, Yoon BH, Edwin S, Mazor M, Chaiworapongsa T. Blood pH and gases in fetuses in preterm labor with and without systemic inflammatory response syndrome. Journal of Maternal-Fetal and Neonatal Medicine 2012 July, 25(7): 1160-70 74. Ross TM, Bhardwaj N, Bissel SJ, Hartman AL, Smith DR. Animal models of Rift Valley fever virus infection. Virus Research 2012 Mar 163(2): 417-423 75. Safronetz D, Ebihara H, Feldmann H, Hooper JW. The Syrian hamster model of hantavirus pulmonary syndrome. Antiviral Research 2012 Sept, 95(3): 282-92 76. Sampath R, Mulholland N, Blyn LB, Massire C, Whitehouse CA, Waybright N, Harter C, Bogan J, Miranda MS, Smith D, Baldwin C, Wolcott M, Norwood D, Kreft R, Frinder M, Lovari R, Yasuda I, Matthews H, Toleno D, Housley R, Duncan D, Li F, Warren R, Eshoo MW, Hall TA, Hofstadler SA, Ecker DJ. Comprehensive Biothreat Cluster Identification by PCR/Electrospray-Ionization Mass Spectrometry. PLoS One 2012 7(6): e36528 77. Schmaljohn C, Mandl CW. The interface of animal and human vaccines. Current Opinion in Virology 2012 June, 2(3): 306-308 78. Schmaljohn CS, Smith LA, Friedlander AM. Military vaccines in today's environment. Human Vaccines & Immunotherapeutics 2012 Aug, 8(8): 1126-1128 79. Shipley MA, Koehler JW, Kulesh DA, Minogue TD. Comparison of nucleic acid extraction platforms for detection of select biothreat agents for use in clinical resource limited settings. Journal of Microbiological Methods 2012 Oct, 91(1): 179 - 183 80. Shurtleff AC, Nguyen TL, Kingery DA, Bavari S. Therapeutics for filovirus infection: traditional approaches and progress towards in silico drug design. Expert Opinion on Drug Discovery 2012 Oct, 7(10): 935-54 81. Silva LP, Vanzile M, Bavari S, Aman JMJ, Schriemer DC. Assembly of ebola virus matrix protein VP40 is regulated by latch-like properties of N and C terminal tails. PLoS One 2012, 7(7): e39978 82. Smith DR, Bird BH, Lewis B, Johnston SC, McCarthy S, Keeney A, Botto M, Donnelly G, Shamblin J, Albarino CG, Nichol ST, Hensley LE. Development of a Novel Nonhuman Primate Model for Rift Valley Fever. Journal of Virology 2012 Feb, 86 (4): 2109-2120 83. Sobarzo A, Perelman E, Groseth A, Dolnik O, Becker S, Lutwama JJ, Dye JM, Yavelsky V, Lobel L, Marks RS. Profiling the Native Specific Human Humoral Immune Response to Sudan Ebola Virus Strain Gulu by Chemiluminescence Enzyme- Linked Immunosorbent Assay. Clinical and Vaccine Immunology 2012 Nov, 19(11): 1844-1852 84. Stanford SM, Panchal RG, Walker LM, Wu DJ, Falk MD, Mitra S, Damle SS, Ruble D, Kaltcheva T, Zhang S, Zhang ZY, Bavari S, Barrios AM, Bottini N. High-throughput screen using a single-cell tyrosine phosphatase assay reveals biologically active

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inhibitors of tyrosine phosphatase CD45. Proceedings of the National Academy of Sciences of the USA 2012 Aug 28, 109(35): 13972-13977 85. Switzer CH, Cheng RY, Ridnour LA, Murray MC, Tazzari V, Sparatore A, Del Soldato P, Hines HB, Glynn SA, Ambs S, Wink DA. Dithiolethiones inhibit NF-kappaB activity via covalent modification in human estrogen receptor-negative breast cancer. Cancer Research 2012 May 1, 72(9): 2394-2404 86. Thomas D, Naughton J, Cote C, Welkos S, Manchester M, Young JAT. Delayed Toxicity Associated with Soluble Anthrax Toxin Receptor Decoy-Ig Fusion Protein Treatment. PLoS One 2012, 7(4): e34611 87. Warren TK, Shurtleff AC, Bavari S. Advanced morpholino oligomers: a novel approach to antiviral therapy. Antiviral Research 2012 Apr, 94(1): 80-8 88. Weinstein SA, Stiles BG. Recent perspectives in the diagnosis and evidence-based treatment of Mycoplasma genitalium. Expert Review of Anti-infective Therapy 2012 Apr, 10(4): 487-99 89. Whitehouse CA, Kesterson KE, Duncan DD, Eshoo MW, Wolcott M. Identification and characterization of Francisella species from natural warm springs in Utah USA. Letters in Applied Microbiology 2012 Apr, 54(4): 313-324 90. Worsham, PL, Mou S, Cote CK, Fritz D. Virulence of Yersinia pseudotuberculosis in aerosol models. Advances in Experimental Medicine and Biology 2012, 954: 217-222 91. Yeager John J, Facemire P, Dabisch PA, Robinson CG, Nyakiti D, Beck K, Baker R, Pitt MLM. Natural History of Inhalation Melioidosis in Rhesus Macaques (Macaca mulatta) and African Green Monkeys (Chlorocebus aethiops.) Infection and Immunity 2012 Sept, 80(9): 3332-3340 92. Zamolo VA, Valenti G, Venturelli E, Chaloin O, Marcaccio M, Boscolo S, Castagnola V, Sosa S, Berti F, Fontanive G, Poli M, Tubaro A, Bianco A, Paolucci F, Prato M. Highly sensitive electrochemiluminescent nanobiosensor for the detection of palytoxin. ACS Nano 2012 Sept. 25, 6(9): 7989-7997 93. Zumbrun EE, Bloomfield HA, Dye JM, Hunter TC, Dabisch PA, Garza N,L Bramel NR, Baker RJ, Williams RD, Nichols DK, Nalca A. A characterization of aerosolized sudan virus infection in African green monkeys cynomolgus macaques and rhesus macaques. Viruses 2012 Oct 15, 4(10): 2115 - 2136

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: To develop medical countermeasures, to include candidate vaccines, diagnostic tests and drug or immunological therapies for biological agents. Perform exploratory studies and advanced development of protective and therapeutic countermeasures and agent

Page 86 of 237 identification technologies.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A, B and C Priority Pathogens

• Overlap Select Agents Including NIAID Category A, B and C Priority Pathogens

• USDA Select Agents and Toxins Including NIAID Category A and B Priority Pathogens

• Other pathogens or toxins Including non-Select Agent, NIAID Category A, B and C Priority Pathogens

(iii) Outdoor Studies: None

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Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Brookhaven National Laboratory

2. Where is it located (provide both address and geographical location)?

Biology Department Upton, New York 11973-5000

3. Floor area of laboratory areas by containment level:

BL2 185 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 185 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 13

(ii) Division of personnel:

Military 0

Civilian 13

(iii) Division of personnel by category:

Scientists 9

Engineers 0

Technicians 4

Administrative and support staff 0

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Biochemistry, Biomedical Science, Cell Biology, Epigenetics, Genetics, Genomics, Molecular Biology, Neuroscience, Protein Chemistry, Protein Crystallography, Protein Engineering, Virology

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(v) Are contractor staff working in the facility? If so, provide an approximate number.

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - wholly

(vii) What are the funding levels for the following program areas:

Research $ 4,130,000 Development $ 0 Test and evaluation $ 0 Total $ 4,130,000

(viii) Briefly describe the publication policy of the facility:

It is the policy of Brookhaven National Laboratory that results of research be published unless publication is expressly restricted by written agreement, and that such publication is an essential part of the work of the Laboratory. The preparation of reviews, articles, monographs, etc. requested by sponsoring organizations and related to sponsored work is considered part of the regular duties of the scientific and technical staff members. Scientists are required to publish their results in the peer reviewed scientific literature as well as present their work at national and international meetings.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

1. Alexieva-Botcheva, K. and Anderson, C. W. p53. Encyclopedia of Signaling Molecules, S. Choi, Editor, Vol. 1, Springer Science + Business Media, LLC, New York, NY (July, 2012). 2. Casjens, S. R., Mongodin, E. F., Qiu, W.-G., Luft, B. J., Schutzer, S. E., Gilcrease, E. B., Huang, W. M., Vujadinovic, M., Aron, J. K., Vargas, L. C., Freeman, S., Radune, D., Weldman, J. F., Dimitrov, G. I., Khouri, H. M., Sosa, J. E., Halpin, R. A., Dunn, J. J., and Fraser, C. M. Genome stability of Lyme disease spirochetes: Comparative genomics of Borrelia burgdorferi plasmids. PLoS One 7(3): e33280 (March, 2012). 3. Schutzer, S. E., Fraser-Liggett, C. M., Qiu, W.-G., Kraiczy, P., Mongodin, E. F., Dunn, J. J., and Luft, B. J. Whole-genome sequences of Borrelia bissettii, Borrelia valaisiana,

Page 89 of 237

and Borrelia spielmanii. Journal of Bacteriology 194(2): 545-546 (January, 2012). 4. Yao, Q., Song, C. X., He, C., Kumaran, D., and Dunn, J. J. Heterologous expression and purification of Arabidopsis thaliana VIM1 protein: In vitro evidence for its inability to recognize hydroxymethylcytosine, a rare base in Arabidopsis DNA. Protein Expression and Purification 83(1): 104-111 (May, 2012). 5. Tawde, M. D. and Freimuth, P. Toxic misfolding of Arabidopsis cellulases in the secretory pathway of Pichia pastoris. Protein Expression and Purification 85(2): 211- 217 (October, 2012). 6. Baniecki, M. L., McGrath, W. J., and Mangel, W. F. Regulation of a viral proteinase by a peptide and DNA in one-dimensional space. III. Atomic resolution structure of a nascent form of the adenovirus proteinase. Journal of Biological Chemistry (Epub October 7, 2012). 7. Blainey, P. C., Graziano, V., Perez-Berna, A. J., McGrath, W. J., Flint, S. J., San Martin, C., Xie, X. S., and Mangel, W. F. Regulation of a viral proteinase by a peptide and DNA in one-dimensional space. IV. Viral proteinase slides along DNA to locate and process its substrates. Journal of Biological Chemistry (Epub October 7, 2012). 8. Graziano, V., Luo, G., Blainey, P. C., Perez-Berna, A. J., McGrath, W. J., Flint, S. J., San Martin, C., Xie, X. S., and Mangel, W. F. Regulation of a viral proteinase by a peptide and DNA in one-dimensional space. II. Adenovirus proteinase is activated in an unusual one-dimensional biochemical reaction. Journal of Biological Chemistry (Epub October 7, 2012). 9. Graziano, V., McGrath, W. J., Suomalainen, M., Greber, U. F., Freimuth, P., Blainey, P. C., Luo, G., Xie, X. S., and Mangel, W. F. Regulation of a viral proteinase by a peptide and DNA in one-dimensional space. I. Binding to DNA and to hexon of the precursor to protein VI, pVI, of human adenovirus. Journal of Biological Chemistry (Epub October 7, 2012). 10. Agarwal, R., Burley, S. K., and Swaminathan, S. Structural insight into mechanism and diverse substrate selection strategy of L-ribulokinase. PROTEINS: Structure, Function, and Bioinformatics 80(1): 261-268 (January, 2012). 11. Eswaramoorthy, S., Poulain, S., Hienerwadel, R., Bremond, N., Sylvester, M. D., Zhang, Y.-B., Berthomieu, C., van der Lelie, D., and Matin, A. Crystal structure of ChrR-A quinone reductase with the capacity to reduce chromate. PLoS One 7(4): e36017 (April, 2012). 12. Kumar, G., Agarwal, R., and Swaminathan, S. Discovery of a fluorene class of compounds as inhibitors of Botulinum neurotoxin serotype E by virtual screening. Chemical Communications 48(18): 2412-2414 (February, 2012). 13. Kumar, G., Kumaran, D., Ahmed, S. A., and Swaminathan, S. Peptide inhibitors of botulinum neurotoxin serotype A: Design, inhibition, cocrystal structures, structure- activity relationship and pharmacophore modeling. Acta Crystallographica D: Biological Crystallography D68(Pt5): 511-520 (May, 2012). Cover: Botulinum

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neurotoxin serotype A with inhibitor RRGF, p. 511. 14. Lakshminarasimhan, D., Kumaran, D., Agarwal, R., Singh, B. R., and Swaminathan, S. Cloning, expression and purification of botulinum neurotoxin type A heavy chain - crystallographic evidence for a putative tetrameric pore. The Botulinum Journal 2(2): 135-149 (October, 2012). 15. Lu, X., Zhou, R., Sharma, I., Li, X., Kumar, G., Swaminathan, S., Tonge, P. J., and Tan, D. S. Stable analogues of OSB-AMP: Potent inhibitors of MenE, the o- succinylbenzoate-CoA synthetase from bacterial menaquinone biosynthesis. ChemBioChem 13(1): 129-136 (January, 2012). 16. Palani, K., Kumaran, D., Burley, S. K., and Swaminathan, S. Structure of a periplasmic glucose-binding protein from Thermotoga maritima. Acta Crystallographica Section F: Structural Biology and Crystallization Communications 68(Pt2): 1460-1464 (December, 2012).

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: The majority of the agents are not used for biodefense related work. The overall objective of the project that is biodefense related (DOD supported) is to develop countermeasures for biowarfare agents. The specific aim of the project is to determine the three-dimensional structures of the agents. The purified agents are crystallized using standard crystallization techniques and brought to the National Synchrotron Light Sources (also at Brookhaven National Laboratory) for x-ray diffraction studies. These results can lead to vaccine development, treatment, and/or diagnosis. BNL is registered with the CDC Select Agent Program for this work.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A Priority Pathogens

• Other pathogens or toxins

(iii) Outdoor Studies: None

Page 91 of 237

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Idaho National Laboratory

2. Where is it located (provide both address and geographical location)?

2525 Fremont Ave. Idaho Falls, Idaho 83415-2203

3. Floor area of laboratory areas by containment level:

BL2 90 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 90 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 3

(ii) Division of personnel:

Military 0

Civilian 3

(iii) Division of personnel by category:

Scientists 3

Engineers 0

Technicians 0

Administrative and support staff 0

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Genomics, Microbiology, Molecular Biology, Wildlife Health-Decontamination Efficacy Study

Page 92 of 237

(v) Are contractor staff working in the facility? If so, provide an approximate number.

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Environmental Protection Agency (EPA)

(vii) What are the funding levels for the following program areas:

Research $ 0 Development $ 0 Test and evaluation $ 10,000 Total $ 10,000

(viii) Briefly describe the publication policy of the facility:

Publication is encouraged but must meet customer requirements and export control restrictions.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

None published during that period.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: Viability testing subsequent to decontamination using Bacillus atrophaeus as a simulant for B. anthracis. No funded work with Brucella in 2012, but viable culture collection is maintained.

(ii) Agents Microorganisms and/or Toxins:

• Overlap Select Agents Including NIAID Category B Priority Pathogens

Page 93 of 237

• Other pathogens or toxins

(iii) Outdoor Studies: None

Page 94 of 237

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Lawrence Berkeley National Laboratory (LBNL)

2. Where is it located (provide both address and geographical location)?

1 Cyclotron Road Berkeley, California 94720

3. Floor area of laboratory areas by containment level:

BL2 130 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 130 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 6

(ii) Division of personnel:

Military 0

Civilian 6

(iii) Division of personnel by category:

Scientists 3

Engineers 0

Technicians 3

Administrative and support staff 0

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Bacteriology, Bioinformatics, Biology, Computational Biology, Ecology, Environmental Science, Genomics, Microbial Forensics, Microbiology, Molecular Biology

Page 95 of 237

(v) Are contractor staff working in the facility? If so, provide an approximate number.

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Health and Human Services (HHS)

(vii) What are the funding levels for the following program areas:

Research $ 200,000 Development $ 0 Test and evaluation $ 0 Total $ 200,000

(viii) Briefly describe the publication policy of the facility:

The mission of Lawrence Berkeley National Laboratory is to generate and disseminate knowledge in the public interest. Essential to this mission are two fundamental principles: open scholarly exchange and academic freedom. Normally, these principles are mutually supportive. On those rare occasions when they conflict, they must be balanced, taking into account LBNL's mission and the public interest. LBNL has also has had a longstanding tradition of conducting research aimed at enhancing human life and the human condition.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

None

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: No biological defense work currently. We are writing manuscripts from previous biological defense work on strain typing in Francisella. We currently have no live isolates or DNA from any Select Agent.

(ii) Agents Microorganisms and/or Toxins:

Page 96 of 237

None

(iii) Outdoor Studies: None

Page 97 of 237

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Lawrence Livermore National Laboratory (LLNL)

2. Where is it located (provide both address and geographical location)?

Lawrence Livermore National Laboratory 7000 East Avenue

Livermore, California 94550

3. Floor area of laboratory areas by containment level:

BL2 1563 (sqM) BL3 60 (sqM) BL4 0 (sqM) Total laboratory floor area 1623 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 106

(ii) Division of personnel:

Military 0

Civilian 106

(iii) Division of personnel by category:

Scientists 56

Engineers 8

Technicians 14

Administrative and support staff 28

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Aerosol Science, Analytical Biochemistry, Analytical Mass Spectrometry, Bacteriology, Biochemistry, Bioengineering, Bioinformatics, Biology, Biomedical Engineering,

Page 98 of 237

Biomedical Science, Biophysics, Biotechnology, Chemical Engineering, Chemistry, Computer Science, Environmental Science, Epidemiology, Immunology, Infectious Disease, Mass Spectrometry, Mass Spectrometry Biochemistry, Microbial Forensics, Microbiology, Microfluidics, Molecular Biology, Molecular Computational Biology, Nanotechnology, Pharmacology, Plant Biotechnology, Proteomics, Toxicology, Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - partly U.S. Department of Energy (DOE) U.S. Department of Health and Human Services (HHS) U.S. Department of Homeland Security (DHS) U.S. Environmental Protection Agency (EPA) Internal (Laboratory Directed Research and Development LDRD) Other Governmental Agencies

(vii) What are the funding levels for the following program areas:

Research $ 17,772,000 Development $ 0 Test and evaluation $ 3,054,000 Total $ 20,826,000

(viii) Briefly describe the publication policy of the facility:

Lawrence Livermore National Laboratory's (LLNL) publication policy is contained in the "LLNL Information Management Policy" (January 2008). Prior to publication, document content including scientific, technical and programmatic information is reviewed and released by the author's directorate, the Office of Classification and Export Control, and/or the Industrial Partnerships Office, as appropriate. Subject matter experts may also be required to review documents based on the content. Every year, authors at LLNL create thousands of documents. These documents are widely varied in scientific, technical, programmatic, and administrative content and scope. Some documents are written for the scientific community outside the Laboratory and some are written for the general public. Some documents are written for a more limited audience. Reviews are conducted prior to

Page 99 of 237

publication to determine availability of information, or restrictions thereto. These reviews include, but are not limited to, the following: 1) classification/declassification, 2) copyrighted materials or other intellectual property, 3) export controls or distribution restrictions, and 4) sensitive content that requires limits to access. The LLNL Information Management Policy ensures that unclassified and classified scientific and technical information resulting from LLNL research is identified, processed, disseminated, and preserved in accordance with our contract and DOE requirements.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

1. M.K. Borucki, Allen JE, Chen-Harris H, Zemla A, Vanier G, et al. (in press) The Role of Viral Population Diversity in Adaptation of Bovine Coronavirus to New Host Environments. PLoS ONE 8(1): e52752. Epub 2013 Jan 7.

2. P. R. Kumaresan, S. Devaraj, W. Huang, E. Y. Lau, R. Liu, K. S. Lam, I. Jialal. Synthesis and Characterization of a Novel Inhibitor of C-Reactive Protein-Mediated Proinflammatory Effects. Metabolic Syndrome and Related Disorders. Epub ahead of print. 2013 Feb 27. PubMed PMID: 23445482.

3. L. Dugan, J. Bearinger, A. Hinckley, C. Strout, B. Souza. Detection of Bacillus anthracis from Spores and Cells by Loop-mediated Isothermal Amplification without Sample Preparation. J. Microbiolo. Methods. 90(3):280-4. Epub 2012 Jun 5.

4. A. Navid, E. Almaas. Genome-Level Transcription Data of Yersina Pestis Analyzed With A New Metabolic Constraint-Based Approach. BMC Syst Biol 6(1): 150. (December 2012).

5. T. S. Carpenter, E. Y. Lau, F. C. Lightstone. A Molecular Dynamics Study on the Effect of Disulfide Bonds in Cys-Loop Ligand-Gated GABAA Receptors. Biophysical Journal 102(3): 111a. (January 2012).

6. A. Parker. Building New Vaccines for the 21st Century. Science & Technology Review. p.6-13. (September 2012).

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: LLNL is performing work in the area of biological agent detection, therapeutics development, virulence mechanism elucidation, structural characterization, agent viability testing, response planning, restoration, and forensics. The biological detection platforms are

Page 100 of 237 being developed. These platforms use PCR, immunoassay, mass spectrometry and genomic sequencing to gather useful information about the biological species present in the sampling environment. LLNL is also working to support and upgrade the BioWatch biological detection network put in place by the Department of Homeland Security (DHS). Personnel from LLNL play an important role in the bioinformatics required to develop new detection assays for various detection platforms. The development and screening of new nucleic acid- based assays are also core areas of expertise at LLNL. Testing and validation of new hardware components as well as training for the BioWatch network are other areas where LLNL supports the DHS mission. In addition to the detection platforms LLNL is also working on tools that will help restore normal activities in the event of a biological incident. These include developing rapid viability testing, decontamination strategies, and biological response plans for DHS, DOD, and EPA. We also have substantial activities in developing forensic assays to help determine the geographic origin of an agent and who might be responsible for the use of that agent. Beyond detection, response, recovery, and attribution LLNL also has ongoing research projects to elucidate host-pathogen interactions. The goal of this research is to understand how microorganism is able to defeat or circumvent the host immune system. This will enable the development of new intervention strategies specifically targeted to steps in the microorganism life cycle. LLNL is also involved in the search for new compounds as well as the development of novel vaccine strategies for disease prevention. This work involves stimulating either innate or adaptive immunity for prophylaxis and therapeutics.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A and B Priority Pathogens

• Overlap Select Agents Including NIAID Category A and B Priority Pathogens

• Other pathogens or toxins Including non-Select Agent, NIAID Category B and C Priority Pathogens

(iii) Outdoor Studies: None

Page 101 of 237

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Los Alamos National Laboratory (LANL)

2. Where is it located (provide both address and geographical location)?

Bikini Atoll Road SM-30 43-0001-01U

Los Alamos, New Mexico 87545

3. Floor area of laboratory areas by containment level:

BL2 498 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 498 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 34

(ii) Division of personnel:

Military 0

Civilian 34

(iii) Division of personnel by category:

Scientists 20

Engineers 1

Technicians 13

Administrative and support staff 0

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Biochemistry, Bioinformatics, Biology, Cell Biology, Environmental Science, Genomics, Infectious Disease, Microbial Forensics, Microbiology, Molecular Biology, Molecular

Page 102 of 237

Pathogenic Microbiology, Pathogenesis, Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - partly U.S. Department of Energy (DOE) U.S. Department of Health and Human Services (HHS) U.S. Department of Homeland Security (DHS) U.S. Department of Justice (DOJ) Internal (Laboratory Directed Research and Development LDRD)

(vii) What are the funding levels for the following program areas:

Research $ 12,633,000 Development $ 1,600,000 Test and evaluation $ 0 Total $ 14,233,000

(viii) Briefly describe the publication policy of the facility:

As a Department of Energy National Nuclear Security Administration (DOE/NNSA) facility, LANL is required to make scientific and technical information broadly available, within applicable laws and Departmental requirements, to accomplish mission objectives and strategic goals, promote scientific advancement, satisfy statutory dissemination requirements, and ensure a fair return on Departmental and taxpayer investment. The Laboratory has a mandate to ensure that scientific and technical information is identified, processed, disseminated, and preserved to enable the scientific community and the public to locate and use the unclassified and unlimited-distribution information resulting from DOE research and related endeavors. The Laboratory also has procedures in place to manage and protect classified, sensitive controlled unclassified, and export-controlled scientific and technical information, yet make it accessible for appropriate access by the Department, its contractors, and others. Reviews are conducted prior to publication to determine availability of information, or restrictions thereto. These reviews include, but are not limited to, the following: 1) classification/declassification, 2) copyrighted materials or other intellectual property, 3) export controls or distribution restrictions, and 4) sensitive content

Page 103 of 237 that requires limits to access.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

1. Nowak-Lovato K, Alexandrov LB, Banisadr A, Bauer AL, Bishop AR, Usheva A, Mu F, Hong-Geller E, Rasmussen K, Hlavacek WS, and Alexandrov BS. (2013) Binding of Nucleoid-associated Protein Fis to DNA is Regulated by DNA Breathing Dynamics. PLoS Comp. Biol. Jan;9(1):e1002881. doi: 10.1371/journal.pcbi.1002881. 2. Marti-Arbona R, Teshima M, Anderson PS, Nowak-Lovato K, Hong-Geller E, Unkefer C, and Unkefer P. (2012) Identification of new ligands for the methionine biosynthesis transcriptional regulator (MetJ) by FAC-MS. J. Mol Microbiol Biotech. 22: 205-214. 3. Novak-Lovato K, Hickmott AJ, Maity, TS, Bulyk ML, Dunbar J, and Hong-Geller E. (2012) DNA binding site analysis of Burkholderia thailandensis response regulators. J. Microbiol. Methods. 90:46-52. 4. Taylor-McCabe, K, Shou, Y, and Hong-Geller, E. (2012) Effects of Bacillus anthracis hydrophobicity and induction of host cell death on sample collection from environmental surfaces. J. Gen. Appl. Microbiology. 58: 113-119. 5. Maity, TS, Close, DW, Valdez, YE, Nowak-Lovato, K, Marti-Arbona, R, Nguyen, TT, Unkefer, PJ, Hong-Geller, E, Bradbury, AR, and Dunbar, JM (2012) Discovery of DNA operators for TetR and MarR family transcription factors from Burkholderia xenovorans. Microbiology. 158: 571-82.

6. KK Hill and TJ Smith. Genetic diversity within Clostridium botulinum serotypes, botulinum neurotoxin gene clusters and toxin subtypes. 2012. Springer Publishing. Current Topics in Microbiology and Immunology, pgs 1-20. 7. SA Ahmed, J Awosika, C Baldwin, KA Bishop-Lilly, B Biswas, S Broomall, PSG Chain, O Chertkov, O Chokoshvili, S Coyne, K Davenport, JC Detter, W Dorman, TH Erkkila, JP Folster, KG Frey, M George, C Gleasner, M Henry, KK Hill, K Hubbard, J Insalaco, S Johnson, A Kitzmiller, M Krepps, C-C Lo, T Luu, LA McNew, T Minogue, CA Munk, B Osborne, M Patel, KG Reitenga, CN Rosenzweig, A Shea, X Shen, N Strockbine, C Tarr, H Teshima, E van Gieson, K Verratti, M Wolcott, Ga Xie, S Sozhamannan, HS Gibbons. Genomic comparison of Escherichia coli O104:H4 isolates from 2009 and 2011 reveals plasmid, and prophage heterogeneity, including shiga toxin encoding phage stx2., PLoS One. 2012;7(11):e48228. doi: 10.1371/journal.pone.0048228. Epub 2012 Nov 1. 8. Siddaramappa S, JF Challacombe, JM Petersen, S Pillai, CR Kuske (2012) Genetic diversity within the genus Francisella as revealed by comparative analyses of the genomes of two North American isolates from environmental sources. BMC Genomics 13:422

Page 104 of 237

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: The biological defense research and development activities at the Los Alamos National Laboratory include pathogen signature identification, host-pathogen interaction characterization, biothreat agent virulence study, and pathogen detection and analysis technologies. The main objectives for the studies are to: understand molecular mechanisms of host-pathogen interaction, study molecular, chemical, and physical signatures of biothreat agents for pathogen detection and characterization; study microbial organism genetic variations for detection assay design and improvement; evaluate detection assay and platform performance; develop DNA, RNA and protein based detection and bioforensics assays; develop next generation high throughput microbial sequencing and finishing capabilities; develop high throughput assays for host-pathogen protein interactions screening; identify host molecular targets as potential therapeutic candidates; develop and validate assays to improve the ability to identify and characterize an incidence of bioterrorism against humans or agriculture; assess the feasibility of pathogen detection for environmental monitoring procedures with commercially available DNA extraction and purification techniques; and perform viral and bacterial pathogen sequencing for characterization, comparative genomic analysis, and metagenomic analysis.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A and B Priority Pathogens

• Other pathogens or toxins Including non-Select Agent, NIAID Category B Priority Pathogens

(iii) Outdoor Studies: None

Page 105 of 237

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Pacific Northwest National Laboratory (PNNL)

2. Where is it located (provide both address and geographical location)?

902 Battelle Boulevard Richland, Washington 99352

3. Floor area of laboratory areas by containment level:

BL2 679 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 679 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 23

(ii) Division of personnel:

Military 0

Civilian 23

(iii) Division of personnel by category:

Scientists 21

Engineers 0

Technicians 0

Administrative and support staff 2

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Analytical Biochemistry, Analytical Chemistry, Analytical Mass Spectrometry, Bacteriology, Biochemistry, Cell Biology, Chemistry, Genomics, Infectious Disease, Mass Spectrometry, Mass Spectrometry Biochemistry, Microbial Forensics, Microbiology,

Page 106 of 237

Molecular Biology, Molecular Pathogenic Microbiology, Nanotechnology, Protein Chemistry, Proteomics, Structural Biology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - partly U.S. Department of Health and Human Services (HHS) U.S. Department of Homeland Security (DHS) Internal (Laboratory Directed Research and Development LDRD)

(vii) What are the funding levels for the following program areas:

Research $ 5,342,000 Development $ 0 Test and evaluation $ 0 Total $ 5,342,000

(viii) Briefly describe the publication policy of the facility:

Publication in the open literature is encouraged. Each document must pass through an internal clearance mechanism that includes technical review, review by an authorized derivative classifier, review by the office of export control and the project manager. In most cases, the funding source is consulted prior to a document being submitted for publication or release to the public.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

1. D.S. Wunschel, A.M. Melville, C.J. Ehrhardt, H.A. Colburn, K.D. Victry, K.C. Antolick, J.H. Wahl, K.L. Wahl. 2012. Integration of Gas Chromatography Mass Spectrometry Methods for Differentiating Ricin Preparation Methods. Analyst, 137(9), 2077-2085 (2012). 2. Cliff, J.B., H.W. Kreuzer, D.S. Wunschel, and C. J. Ehrhardt, eds., 2012, Chemical and Physical Methods for Microbial Forensics, Springer, New York Kreuzer, H.W. "Stable

Page 107 of 237

isotope signatures for microbial forensics", 2012, In: Chemical and Physical Methods for Microbial Forensics, Cliff, Kreuzer, Wunschel, and Ehrhardt, eds., Springer, New York. 3. Wunschel DS, AM Melville, CJ Ehrhardt, HA Colburn, KD Victry, KC Antolick, JH Wahl, KL Wahl. 2012. "Integration of gas chromatography mass spectrometry methods for differentiating ricin preparation methods". Analyst 137: 2077-2085. 4. Wunschel, DS, A Fox, KL Wahl. "Glycoprotein and Protein Markers for Strain Differentiation and Growth Environment or Media Attribution". 61-70, 2012. In Chemical and Physical Signatures for Microbial Forensics. Eds. JB Cliff, HW Kreuzer, CJ Ehrhardt, DS Wunschel, Humana Press, Springer, NY. 5. Wahl KL. "Extracellular Signatures as Indicators of Process Methods". 107-116, 2012. In Chemical and Physical Signatures for Microbial Forensics. Eds. JB Cliff, HW Kreuzer, CJ Ehrhardt, DS Wunschel, Humana Press, Springer, NY. 6. Schrimpe-Rutledge AC, Jones MB, Chauhan S, Purvine SO, Sanford JA, Monroe ME, Brewer HM, Payne SH, Ansong C, Frank BC, Smith RD, Peterson SN, Motin VL, Adkins JN.Comparative omics-driven genome annotation refinement: application across Yersiniae.PLoS One. 2012;7(3):e33903. doi: 10.1371/journal.pone.0033903. Epub 2012 Mar 27. 7. Ansong C, Deatherage BL, Hyduke D, Schmidt B, McDermott JE, Jones MB, Chauhan S, Charusanti P, Kim YM, Nakayasu ES, Li J, Kidwai A, Niemann G, Brown RN, Metz TO, McAteer K, Heffron F, Peterson SN, Motin V, Palsson BO, Smith RD, Adkins JN. Studying salmonellae and yersiniae host-pathogen interactions using integrated 'omics and modeling.Curr Top Microbiol Immunol. 2013;363:21-41. doi: 10.1007/82_2012_247. 8. Brown RN, Sanford JA, Park JH, Deatherage BL, Champion BL, Smith RD, Heffron F, Adkins JN. A Comprehensive Subcellular Proteomic Survey of Salmonella Grown under Phagosome-Mimicking versus Standard Laboratory Conditions.Int J Proteomics. 2012;2012:123076. doi: 10.1155/2012/123076. Epub 2012 Jul 25.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: The primary objectives of the of the biodefense work being conducted at PNNL are: 1) develop analytical methods for identifying organic signatures of processing methods, procedures, and materials used in culturing and preparation of biological hazards, and to determine protein, carbohydrate and lipid changes in pathogens with variations in culture

conditions and food source; 2) investigate nucleic acid and immunoassay detection methods for biological threat agents and to be able to discriminate those agents from non- pathogenic near neighbors; 3) investigate methods for detection and determination of food and waterborne pathogens and develop protocols to rapidly culture low yield organisms to

Page 108 of 237 enhance detection; 4) use mass spectrometric tools to elucidate functional changes in the proteomes of infectious bacteria under relevant growth conditions, host-derived cell-lines during infection, or with overexpressed pathogen secreted proteins; 5) evaluate next generation biodetection systems and approaches; and 6) study the basic infectious properties of Salmonella and Yersinia using a systems biology approach, then applying proteomics and metabolomics measurements to analyze those samples. In the case of Yersinia pestis, the bacteria are killed and prepared prior to being sent to PNNL for analysis.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category B Priority Pathogens

• Other pathogens or toxins Including non-Select Agent, NIAID Category B Priority Pathogens

(iii) Outdoor Studies: None

Page 109 of 237

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Sandia National Laboratories (SNL)

2. Where is it located (provide both address and geographical location)?

P. O. Box 5800 Albuquerque, New Mexico 87185

3. Floor area of laboratory areas by containment level:

BL2 1366 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 1366 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 109

(ii) Division of personnel:

Military 0

Civilian 109

(iii) Division of personnel by category:

Scientists 77

Engineers 3

Technicians 25

Administrative and support staff 4

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Aerobiology, Analytical Biochemistry, Analytical Chemistry, Analytical Mass Spectrometry, Bacteriology, Biochemistry, Bioengineering, Bioenvironmental Engineering, Biofuel Production, Bioinformatics, Bioinorganic Chemistry, Biological Control, Biology,

Page 110 of 237

Biomedical Engineering, Biomedical Science, Biophysics, Biotechnology, Cell Biology, Chemical Engineering, Chemistry, Computational Biology, Computer Engineering, Computer Science, Downstream Processing Protein Purification, Electrical Engineering, Electronic Engineering, Engineering, Environmental Engineering, Environmental Science, Epigenetics, Food and Water Testing, General Engineering, Genetics, Genomics, Geosciences, Health Science, High Throughput Sequencing, Immunology, Infectious Disease, Laser Eletcro-Optics, Mass Spectrometry, Mass Spectrometry Biochemistry, Materials Science, Mathematics, Mechanical Engineering, Microbial Forensics, Microbiology, Microfluidics, Molecular Biology, Molecular Computational Biology, Molecular Pathogenic Microbiology, Molecular Spectroscopy and Imaging, Molecular Toxicology, Nanotechnology, Neuroscience, Operations Research Analysis, Optical Spectroscopy, Parasitology, Pathogenesis, Pathology, Physical Science, Physics, Physiology, Plant Biochemistry, Plant Biotechnology, Plant Molecular Biology, Plant Pathology, Plant Physiology, Plant Virology, Polymer Science, Protein Chemistry, Protein Crystallography, Protein Engineering, Proteomics, Rickettsiology, Structural Biology, Systems Engineering, Toxicology, Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 9

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - partly U.S. Department of Energy (DOE) U.S. Department of Health and Human Services (HHS) U.S. Department of Homeland Security (DHS) Internal (Laboratory Directed Research and Development LDRD) Other Governmental Agencies

(vii) What are the funding levels for the following program areas:

Research $ 28,156,000 Development $ 550,000 Test and evaluation $ 751,000 Total $ 29,457,000

(viii) Briefly describe the publication policy of the facility:

Page 111 of 237

Scientists are encouraged to publish their results in the peer-reviewed scientific literature as well as present their work at national and international professional meetings.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

1. Aaron, JS and Timlin, JA, "Advanced Optical Imaging of Endocytosis," in Molecular Recognition of Endocytosis: B. Ceresa (Ed.), InTech Publishing. Aaron, JS, Carson, BD, and Timlin, JA, Characterization of Differential Toll-Like Receptor Responses below the Optical Diffraction Limit", Small, 2012, in press. 8;8(19):3041-9. doi: 10.1002/smll.201200106. Epub 2012 Jul 17. PubMed PMID: 22807232 2. Abhyankar, V. V., and A. V. Hatch. "Thirty-Minute Total Synthesis of Microfluidic Systems and Functionalized Porous Elements Via "Living" Radical Photo- Polymerization." Adv Healthc Mater 1, no. 6 (2012): 773-8. 3. Altman, S. J., M. Hibbs, P. B. Savage, H. D. T. Jones, S. Branda, L. K, McGrath, Y. Feng, M. F. Kirk, J. Pollard, A. Lichtenberger, C. Marry, S. Stafslien, D. Goeres and K. Buckingham-Meyer, Linking Ceragenins to Water-Treatment Membranes to Minimize Biofouling, SAND2012- 0181, Sandia National Laboratories, Albuquerque, NM, 2012. 4. Harper JC, Brozik SM, Brinker CJ, Kaehr B. Biocompatible microfabrication of 3D isolation chambers for targeted confinement of individual cells and their progeny. Analytical chemistry 84:21 2012 Nov 6 pg 8985-9. 5. Anderson, P. C., V. De Sapio, K. B. Turner, S. P. Elmer, D. C. Roe, and J. S. Schoeniger. "Identification of Binding Specificity-Determining Features in Protein Families." Journal of Medicinal Chemistry 55, no. 5 (2012): 1926-1939. 6. Ashley CE, Carnes EC, Epler KE, Padilla DP, Phillips GK, Castillo RE, Wilkinson DC, Wilkinson BS, Burgard CA, Kalinich RM, Townson JL, Chackerian B, Willman CL, Peabody DS, Wharton W, Brinker CJ. 2012. Delivery of Small Interfering RNA by Peptide-Targeted Mesoporous Silica Nanoparticle-Supported Lipid Bilayers. ACS Nano 6: 2174-88 (COVER) 7. Bachand, G.D., Allen, A., Bachand, M., Achyuthan, K., Seagrave, J.C., and Brozik, S.M. (2012). Cytotoxicity and inflammation in human alveolar epithelial cells following exposure to occupational levels of gold and silver nanoparticles. J. Nanopart. Res. 14(10): 1-10. 8. Bachand, M., and Bachand, G.D. (2012). Effects of potential environmental interferents of kinesin-powered molecular shuttles. Nanoscale 4(12): 3706-3710. 9. Barter, G. E., D. Reichmuth, J. Westbrook, L. A. Malczynski, T. H. West, D. K. Manley, K. D. Guzman, and D. M. Edwards. "Parametric Analysis of Technology and Policy Tradeoffs for Conventional and Electric Light-Duty Vehicles." Energy Policy 46, (2012): 473-488.

Page 112 of 237

10. Bouxsein, N.F., Carroll-Portillo, A., Bachand, M., Sasaki, D.Y., and Bachand, G.D. (2012). A continuous network of lipid nanotubes fabricated from the gliding motility of kinesin powered microtubule filaments. Langmuir 28, (in press) 11. Brinker CJ. 2012. Nanoparticle immunotherapy: Combo combat. Nat Mater 11: 831-2 12. Cheng, G., M. S. Kent, L. L. He, P. Varanasi, D. Dibble, R. Arora, K. Deng, K. L. Hong, Y. B. Melnichenko, B. A. Simmons, and S. Singh. "Effect of Ionic Liquid Treatment on the Structures of Lignins in Solutions: Molecular Subunits Released from Lignin." Langmuir 28, no. 32 (2012): 11859-11866. 13. Collins AM, Liberton M, Garcia OF, Jones HDT, Pakrasi HB, and Timlin, JA, "Photosynthetic pigment localization and thylakoid membrane morphology are altered in Synechocystis 6803 phycobilisome mutants," Plant Physiology, 2012, 158(4), 1600- 1609. 14. Davis, R. W., J. V. Volponi, H. D. Jones, B. J. Carvalho, H. Wu, and S. Singh. "Multiplex Fluorometric Assessment of Nutrient Limitation as a Strategy for Enhanced Lipid Enrichment and Harvesting of Neochloris Oleoabundans." Biotechnol Bioeng 109, no. 10 (2012): 2503-12. 15. Deng, K., K. W. George, W. Reindl, J. D. Keasling, P. D. Adams, T. S. Lee, A. K. Singh, and T. R. Northen. "Encoding Substrates with Mass Tags to Resolve Stereospecific Reactions Using Nimzyme." Rapid Communications in Mass Spectrometry 26, no. 6 (2012): 611-615. 16. Fu, L-Y., Cummins, T. R., and Moczydlowski, E. G. 2012. Sensitivity of cloned muscle, heart, and neuronal voltage-gated sodium channels to block by polyamines: a possible basis for modulation of excitability in vivo. Channels, 6: 41-49. 17. Gillespie, J. J., V. Joardar, K. P. Williams, T. Driscoll, J. B. Hostetler, E. Nordberg, M. Shukla, B. Walenz, C. A. Hill, V. M. Nene, A. F. Azad, B. W. Sobral, and E. Caler. "A Rickettsia Genome Overrun by Mobile Genetic Elements Provides Insight into the Acquisition of Genes Characteristic of an Obligate Intracellular Lifestyle." Journal of Bacteriology 194, no. 2 (2012): 376-394. 18. Greving, M., X. L. Cheng, W. Reindl, B. Bowen, K. Deng, K. Louie, M. Nyman, J. Cohen, A. Singh, B. Simmons, P. Adams, G. Siuzdak, and T. Northen. "Acoustic Deposition with Nims as a High-Throughput Enzyme Activity Assay." Analytical and Bioanalytical Chemistry 403, no. 3 (2012): 707-711. 19. Harmon, B., B. R. Schudel, D. Maar, C. Kozina, T. Ikegami, C. T. Tseng, and O. A. Negrete. "Rift Valley Fever Virus Strain Mp-12 Enters Mammalian Host Cells Via Caveola-Mediated Endocytosis." J Virol 86, no. 23 (2012): 12954-70. 20. Harper JC, Brozik SM, Brinker CJ, Kaehr B. 2012. Biocompatible Microfabrication of 3D Isolation Chambers for Targeted Confinement of Individual Cells and Their Progeny. Analytical Chemistry 84: 8985-9 21. Harper JC, Edwards TL, Savage T, Harbaugh S, Kelley-Loughnane N, Stone MO, Brinker CJ, Brozik SM. 2012. Orthogonal Cell-Based Biosensing: Fluorescent,

Page 113 of 237

Electrochemical, and Colorimetric Detection with Silica-Immobilized Cellular Communities Integrated with an ITO-Glass/Plastic Laminate Cartridge. Small 8: 2743- 51 (Cover) 22. Huang, C.-J., Schild, L., and Moczydlowski, E. G. 2012. Use-dependent block of the voltage-gated Na+ channel by tetrodotoxin and saxitoxin: effect of pore mutations that change ionic selectivity. J. Gen. Physiol. 140: 435-454. 23. Gang Cheng, Patanjali Varanasi, Rohit Arora, Vitalie Stavila, Blake A. Simmons, Michael S. Kent, and Seema Singh. Impact of Ionic Liquid Pretreatment Conditions on Cellulose Crystalline Structure Using 1-Ethyl-3-methylimidazolium Acetate. July 23, 2012 (Article). pp 10049-1005. DOI: 10.1021/jp304538v 24. Jebrail, M. J., M. S. Bartsch, and K. D. Patel. "Digital Microfluidics: A Versatile Tool for Applications in Chemistry, Biology and Medicine." Lab on a Chip 12, no. 14 (2012): 2452-2463. 25. Jiang X, Bao L, Cheng Y-S, Dunphy DR, Li X, Brinker CJ. 2012. Aerosol-assisted synthesis of monodisperse single-crystalline [small alpha]-cristobalite nanospheres. Chemical Communications 48: 1293-5 26. Jones, HDT, Haaland, DM, Sinclair, MB, Melgaard, DK, Collins, AM, and Timlin, JA "Preprocessing Strategies to Improve MCR Analyses of Hyperspectral Images," Journal of Chemometrics and Intelligent Laboratory Systems, 2012, in press. Kaehr B, Townson JL, Kalinich RM, Awad YH, Swartzentruber BS, Dunphy DR, Brinker CJ. 2012. Cellular complexity captured in durable silica biocomposites. Proceedings of the National Academy of Sciences 109: 17336-41 27. (Commentary: Ying, J.Y., Cells made of silica. Nature Nanotechnology News & Views 2012, 7, 777-778) 28. Kirk, M. F., E. F. Santillan, L. K. McGrath, and S. J. Altman (2012), Variation in Hydraulic Conductivity with Decreasing pH in a Biologically-Clogged Porous Medium, International Journal of Greenhouse Gas Control, 11, 133-140. 29. Gang Cheng, Michael S. Kent, Lilin He, Patanjali Varanasi, Dean Dibble, Rohit Arora, Kai Deng, Kunlun Hong, Yuri B. Melnichenko, Blake A. Simmons, and Seema Singh. Effect of Ionic Liquid Treatment on the Structures of Lignins in Solutions: Molecular Subunits Released from Lignin. June 26, 2012 (Article). pp 11850-11857. DOI: 10.1021/la300938b 30. Gang Cheng, Zelin Liu, Michael S Kent, Jaroslaw Majewski, Jablin Michael, Murton K Jaclyn, Candice E Halbert, Supratim Datta, Wang Chao, Page Brown. Interactions of Endoglucanases with Amorphous Cellulose Films Resolved by Neutron Reflectometry and Quartz Crystal Microbalance with Dissipation Monitoring. Langmuir , vol. 28, no. 22, pp. 8348-8358, 2012 31. Xiaoyin Xiao, Gabriel A. Montaño, Thayne L. Edwards, Amy Allen, Komandoor E. Achyuthan, Ronen Polsky, David R. Wheeler, and Susan M. Brozik. Surface Charge Dependent Nanoparticle Disruption and Deposition of Lipid Bilayer Assemblies.

Page 114 of 237

Langmuir, Vol 28, Issue 50. pp 17396-17403 32. Lee, S. E., D. Y. Sasaki, Y. Park, R. Xu, J. S. Brennan, M. J. Bissell, and L. P. Lee. "Photonic Gene Circuits by Optically Addressable Sirna-Au Nanoantennas." Acs Nano 6, no. 9 (2012): 7770-7780. 33. Liu, H. and Bachand, G.D. (2012). Effects of confinement on molecular motor-driven self-assembly of ring structures. Mol. Cell. Bioeng. 5: (DOI: 10.1007/s12195-012- 0256-5). 34. Maar, D., B. Harmon, D. Chu, B. Schulz, H. C. Aguilar, B. Lee, and O. A. Negrete. "Cysteines in the Stalk of the Nipah Virus G Glycoprotein Are Located in a Distinct Subdomain Critical for Fusion Activation." Journal of Virology 86, no. 12 (2012): 6632-6642. 35. Mai, J. Y., G. J. Sommer, and A. V. Hatch. "Microfluidic Digital Isoelectric Fractionation for Rapid Multidimensional Glycoprotein Analysis." Analytical Chemistry 84, no. 8 (2012): 3538-3545. 36. Meagher, R. J., and N. Thaitrong. "Microchip Electrophoresis of DNA Following Preconcentration at Photopatterned Gel Membranes." Electrophoresis 33, no. 8 (2012): 1236-1246. 37. Moczydlowski, E. G. 2013. The molecular mystique of tetrodotoxin. Toxicon 63: 165- 183. 38. Padilla D, Pelowitz J, Castillo RE, Epler K, Harper JC, Brinker CJ, Ashley CE, Carnes EC. 2012. Encapsulation of Escherichia coli in a Phospholipid-Templated Silica Nanostructure Enables in situ Quantification of Protein Expression. Small Submitted, August 2012 39. Holland JT, Harper JC, Dolan PL, Manginell MM, Arango DC, et al. (2012)Rational Redesign of Glucose Oxidase for Improved Catalytic Function and Stability.PLoS ONE 7(6):e37924.doi:10.1371/journal.pone.0037924 40. Reichardt, TA, Collins, AM, Garcia, OF, Ruffing, AM, Jones, HDT and Timlin, JA, "Spectroradiometric monitoring of nannochloropsis salina growth," Algal Research, 2012, 1(1), 22-31. 41. JC Harper, TL Edwards, T Savage, S Harbaugh, N Kelley-Loughnane, MO Stone, CJ Brinker, and SM Brozik. 2012. Orthogonal Cell-Based Biosensing: Fluorescent, Electrochemical, and Colorimetric Detection with Silica-Immobilized Cellular Communities Integrated with an ITO-Glass/Plastic Laminate Cartridge. Small. Volume 8, Issue 17, pages 2743-2751. DOI: 10.1002/smll.201200343 42. Spoerke, E.D., Bachand, G.D., Boal, A.K., and Bunker, B.C. (2012). Biodynamic assembly of nanocrystals on artificial microtubule asters. ACS Nano (in press). 43. Stachowiak, J. C., E. M. Schmid, C. J. Ryan, H. S. Ann, D. Y. Sasaki, M. B. Sherman, P. L. Geissler, D. A. Fletcher, and C. C. Hayden. (2012) "Membrane Bending by Protein-Protein Crowding." Nature Cell Biology 14, no. 9 (2012): 944-949. 44. Stavila, V., J. Volponi, A. M. Katzenmeyer, M. C. Dixon, and M. D. Allendorf. Page 115 of 237

"Kinetics and Mechanism of Metal-Organic Framework Thin Film Growth: Systematic Investigation of Hkust-1 Deposition on Qcm Electrodes." Chemical Science 3, no. 5 (2012): 1531-1540. 45. Miller, P. R., Skoog, S. A., Edwards, T. L., Lopez, D. M., Wheeler, D. R., Arango, D. C., Xiao, X. Y., Brozik, S. M., Wang, J., Polsky, R., & Narayan, R. J. (2012). Multiplexed microneedle-based biosensor array for characterization of metabolic acidosis. Talanta2, 88, 739-742. 46. Tarn D, Ashley CE, Xui M, Carnes EC, Zink JI, Brinker CJ. 2012. Mesoporous Silica Nanoparticle Carriers -- Biofunctionality and Biocompatiblility Accounts of Chemical Research In final review, Dec 2012 47. VanderNoot, V., S. Ferko, J. Van De Vreugde, K. Patel, J. Volponi, K. Morrissey, L. Forrest, J. Horton, and B. Haroldsen. "On-Line Monitoring System for Chemical Warfare Agents Using Automated Capillary Micellar Electrokinetic Chromatography." Journal of Chromatography A 1249, (2012): 233-240. 48. Verhoef, L., K. P. Williams, A. Kroneman, B. Sobral, W. van Pelt, M. Koopmans, and Fbve Network. "Selection of a Phylogenetically Informative Region of the Norovirus Genome for Outbreak Linkage." Virus Genes 44, no. 1 (2012): 8-18. 49. Wattam, A. R., T. J. Inzana, K. P. Williams, S. P. Mane, M. Shukla, N. F. Almeida, A. W. Dickerman, S. Mason, I. Moriyon, D. O'Callaghan, A. M. Whatmore, B. W. Sobral, R. V. Tiller, A. R. Hoffmaster, M. A. Frace, C. De Castro, A. Molinaro, S. M. Boyle, B. K. De, and J. C. Setubala. "Comparative Genomics of Early-Diverging Brucella Strains Reveals a Novel Lipopolysaccharide Biosynthesis Pathway." Mbio 3, no. 5 (2012). 50. Wu M, Perroud TD, Srivastava N, Branda CS, Sale KL, Carson BD, Patel KD, Branda SS, Singh AK. Microfluidically-unified cell culture, sample preparation, imaging and flow cytometry for measurement of cell signaling pathways with single cell resolution. Lab Chip. 2012 Aug 21;12(16):2823-31. doi: 10.1039/c2lc40344g. Epub 2012 Jul 10. PubMed PMID: 22777012. 51. Wu, M. Y., and A. K. Singh. "Single-Cell Protein Analysis." Current Opinion in Biotechnology 23, no. 1 (2012): 83-88. 52. Wu, M. Y., T. D. Perroud, N. Srivastava, C. S. Branda, K. L. Sale, B. D. Carson, K. D. Patel, S. S. Branda, and A. K. Singh. "Microfluidically-Unified Cell Culture, Sample Preparation, Imaging and Flow Cytometry for Measurement of Cell Signaling Pathways with Single Cell Resolution." Lab on a Chip 12, no. 16 (2012): 2823-2831. 53. Yilmaz, S., and A. K. Singh. "Single Cell Genome Sequencing." Current Opinion in Biotechnology 23, no. 3 (2012): 437-443. 54. Yu, E., K. Turner, M. Tran-Gyamfi, H. Tran, G. Strobel, C. Taatjes, and M. Hadi. "Secretome Analysis of Endophytic Fungi Grown in Minimally-Treated Lignocellulosic Biomass Feedstocks." Protein Science 21, (2012): 221-221. 55. Zarzar LD, Swartzentruber BS, Harper JC, Dunphy DR, Brinker CJ, Aizenberg J, Kaehr B. 2012. Multiphoton Lithography of Nanocrystalline Platinum and Palladium for Site-

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Specific Catalysis in 3D Microenvironments. Journal of the American Chemical Society 134: 4007-10 56. Zendejas, F. J., P. I. Benke, P. D. Lane, B. A. Simmons, and T. W. Lane. "Characterization of the Acylglycerols and Resulting Biodiesel Derived from Vegetable Oil and Microalgae (Thalassiosira Pseudonana and Phaeodactylum Tricornutum)." Biotechnology and Bioengineering 109, no. 5 (2012): 1146-1154. 57. Zhang H, Dunphy DR, Jiang X, Meng H, Sun B, Tarn D, Xue M, Wang X, Lin S, Ji Z, Li R, Garcia FL, Yang J, Kirk ML, Xia T, Zink JI, Nel A, Brinker CJ. 2012. Processing Pathway Dependence of Amorphous Silica Nanoparticle Toxicity: Colloidal vs Pyrolytic. Journal of the American Chemical Society 134: 15790-804

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: The Sandia Chem/Bio program is an applied research program designed to develop and demonstrate technologies and systems that can be used to mitigate the impact of attacks on civilian populations with chemical or biological agents. Specific aims include: a) analysis of pathogenic mechanisms caused by toxins interacting with cell membranes; b) development of diagnostic and detection technologies for toxins, bacteria, and viruses by applying micro- separations technology; and c) development of technologies for the characterization of aerosolized particles using optics, among many others. Work with biological agents at Sandia also includes work in nanotechnology and biofuels.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A and B Priority Pathogens

• Other pathogens or toxins Including non-Select Agent, NIAID Category A Priority Pathogens

(iii) Outdoor Studies: None

Page 117 of 237

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

CDC, National Center for Environmental Health (NCEH), Division of Laboratory Sciences (DLS)

2. Where is it located (provide both address and geographical location)?

Centers for Disease Control and Prevention U.S. Department of Health and Human Services 4770 Buford Highway

Mail stop F-47 Atlanta, Georgia 30341

3. Floor area of laboratory areas by containment level:

BL2 454 (sqM) BL3 114 (sqM) BL4 0 (sqM) Total laboratory floor area 568 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 19

(ii) Division of personnel:

Military 0

Civilian 19

(iii) Division of personnel by category:

Scientists 19

Engineers 0

Technicians 0

Administrative and support staff 0

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Page 118 of 237

Biochemistry, Biology, Chemistry

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 1

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

Centers for Disease Control and Prevention (CDC)

(vii) What are the funding levels for the following program areas:

Research $ 1,136,260 Development $ 450,000 Test and evaluation $ 911,284 Total $ 2,497,544

(viii) Briefly describe the publication policy of the facility:

Scientists are encouraged to publish their results in the peer reviewed scientific literature as well as present their work at national and international professional meetings.

The clearance policy for information products disseminated outside CDC for public use is available online at: http://www.cdc.gov/od/science/policies

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

1. S.R. Kalb SR, J. Baudys, R.P. Webb, P. Wright, T.J. Smith, L.A. Smith, R. Fernandez, B.H. Raphael, S.E. Maslanka, J.L. Pirkle, and J.R. Barr, Discovery of a Novel Enzymatic Cleavage Site for Botulinum Neurotoxin F5, FEBS Letters, 2012, 586(2), 109-115. 2. S.R. Kalb, J. Baudys, J.C. Rees, T.J. Smith, L.A. Smith, C.H. Helma, K.K. Hill, S. Kull, S. Kirchner, M.B. Dorner, B.G. Dorner, J.L. Pirkle, and J.R. Barr, De novo Subtype and Strain Identification of Botulinum Neurotoxin Type B through Toxin Proteomics, Analytical and Bioanalytical Chemistry, 2012, 403(1), 215-226. 3. Z.P. Weiner, A.E. Boyer, M. Gallegos-Candela, A.N. Cardani, J.R. Barr, I.J. Glomski, Debridement increases survival in a mouse model of subcutaneous anthrax, PLoS One,

Page 119 of 237

2012, 7(2):e30201. 4. D. Wang, J. Baudys, J. Rees, K.M. Marshall, S.R. Kalb, B.A. Parks, L. Nowaczyk, J.L. Pirkle, and J.R. Barr, Subtyping Botulinum Neurotoxins by Sequential Multiple Endoproteases In-gel Digestion Coupled with Mass Spectrometry, Analytical Chemistry, 2012, 84(11), 4652-4658. 5. B.H. Raphael, M. Lautenschlager, A. Kahler, S. Pai, B.A. Parks, S.R. Kalb, S.E. Maslanka, S. Shah, M. Magnuson, and V. Hill, Ultrafiltration improves ELISA and Endopep MS analysis of botulinum neurotoxin type A in drinking water, Journal of Microbiological Methods, 2012, 90(3), 267-272. 6. S.R. Kalb, W.I. Santana, J.L. Pirkle, and J.R. Barr, Detection, Differentiation, and Subtyping of Botulinum Toxins A, B, E, and F by Mass Spectrometry, The Botulism Journal, 2012, 2(2):119-134. 7. B.H. Raphael, M. Lautenschlager, S.R. Kalb, L.I.T. de Jong, M. Frace, C. Luquez, J.R. Barr, R.A. Fernandez, and S.E. Maslanka, Analysis of a unique Clostridium botulinum strain from the Southern hemisphere producing a novel BoNT/E subtype, BMC Microbiology, Oct 31; 12(1), 245. 8. M. Lautenschlager, S.E. Maslanka, P.A. Paul, S.R. Kalb, J.R. Barr, and B.H. Raphael, Recovery and Detection of Botulinum Neurotoxins from a Nonporous Surface, Journal of Microbiological Methods, 2012, Dec 29, S0167-7012(12)00416-2. 9. E.I. Hamelin, R.C. Johnson, J.D. Osterloh, D.J. Howard, J.D. Thomas. Evaluation of Ricinine, a Ricin Biomarker, from a Non-Lethal Castor Bean Ingestion. Journal of Analytical Toxicology. 2012, 36, 9, 660-662

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: The CDC National Center for Environmental Health, Division of Laboratory Science has successfully developed toxin assays that are critical for better detection and diagnosis during a public health response to biological toxins.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A and B Priority Pathogens

(iii) Outdoor Studies: None

Page 120 of 237

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

CDC, Office of Infectious Diseases (OID)

2. Where is it located (provide both address and geographical location)?

Atlanta, GA 1600 Clifton Road N.E.

Atlanta, Georgia 30333

3. Floor area of laboratory areas by containment level:

BL2 294 (sqM) BL3 2331 (sqM) BL4 543 (sqM) Total laboratory floor area 3168 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 184

(ii) Division of personnel:

Military 4

Civilian 180

(iii) Division of personnel by category:

Scientists 160

Engineers 0

Technicians 12

Administrative and support staff 12

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Biochemistry, Biology, Entomology, Epidemiology, Immunology, Medicine, Microbiology, Molecular Biology, Public Health, Statistics, Virology

Page 121 of 237

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 38

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

Centers for Disease Control and Prevention (CDC) U.S. Department of Homeland Security (DHS) U.S. Department of Defense (DOD) - partly U.S. Department of Health and Human Services (HHS) U.S. Department of State (DoS) U.S. Agency For International Development (USAID)

(vii) What are the funding levels for the following program areas:

Research $ 12,780,426 Development $ 3,306,096 Test and evaluation $ 4,262,610 Total $ 20,349,132

(viii) Briefly describe the publication policy of the facility:

Publication is encouraged and managed by editorial and clearance policies conducted at all levels of the Agency.

The clearance policy for information products disseminated outside CDC for public use is available online at: http://www.cdc.gov/od/science/policies

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

1. Adjemian, J., I. B. Weber, J. McQuiston, K. S. Griffith, P. S. Mead, W. Nicholson, A. Roche, M. Schriefer, M. Fischer, O. Kosoy, J. J. Laven, R. A. Stoddard, A. R. Hoffmaster, T. Smith, D. Bui, P. P. Wilkins, J. L. Jones, P. N. Gupton, C. P. Quinn, N. Messonnier, C. Higgins, and D. Wong. "Zoonotic Infections among Employees from Great Smoky Mountains and Rocky Mountain National Parks, 2008-2009." Vector Bourne Zoonotic Dis 12, no. 11 (2012): 922 - 31. 2. Alzahrani, Abdullah G.; Al Shaiban, Hassan M.; Al Mazroa, Mohammad A.; Al- Hayani, Osama; MacNeil, Adam; Rollin, Pierre E., and Memish, Ziad A. Alkhurma

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virus, subtype of Kyasanur Forest disease virus, was described for the first time in 1995 in Saudi Arabia - Response to Dr. Madani's letter. Intervirology. 2012; 55(4):261-262. 3. Amman, Brian R.; Carroll, Serena A.; Reed, Zachary D.; Sealy, Tara K.; Balinandi, Stephen; Swanepoel, Robert; Kemp, Alan; Erickson, Bobbie Rae; Comer, James A. C; Campbell, Shelley; Cannon, Deborah L.; Khristova, Marina L.; Atimnedi, Patrick; Paddock, Christopher D.; Kent Crockett, Rebekah J.; Flietstra, Timothy D.; Warfield, Kelly L.; Unfer, Robert; Katongole-Mbidde, Edward; Downinng, Robert; Tappero, Jordan W.; Zaki, Sherif R.; Rollin, Pierre E.; Ksiazek, Thomas G.; Nichol, Stuart T., and Towner, Jonathan S. Seasonal Pulses of Marburg Virus Circulation in Juvenile Rousettus aegyptiacus Bats Coincide with Periods of Increased Risk of Human Infection. PLoS Pathogens. 2012; 8(10):e1002877. 4. Arndt W, Mitnik C, Denzler KL, White S, Waters R, Jacobs BL, Rochon Y, Olson VA, Damon IK, Langland JO. In vitro characterization of a nineteenth-century therapy for smallpox. PLoS One. 2012; 7(3):e32610. 5. Bagamian, Karoun H.; Douglass, Richard J.; Alvarado, Arlene; Kuenzi, Amy J.; Amman, Brian R.; Waller, Lance A., and Mills, James N. Population density and seasonality effects on Sin Nombre virus transmission in North American deermice (Peromyscus maniculatus) in outdoor enclosures. PLoS One. 2012; 7(6):e37254. 6. Bagamian, Karoun H.; Towner, Jonathan S.; Kuenzi, Amy J.; Douglass, Richard J.; Rollin, Pierre E.; Waller, Lance A., and Mills, James N. Transmission ecology of sin nombre hantavirus in naturally infected north american deermouse populations in outdoor enclosures. PLoS One. 2012; 7(10):e47731. 7. Bergeron, Eric; Chakrabarti, Ayan K.; Bird, Brian H.; Dodd, Kimberly A.; McMullan, Laura K.; Spiropoulou, Christina F.; Nichol, Stuart T., and Albarino, Cesar G. Reverse genetics recovery of Lujo virus and role of virus RNA secondary structures in efficient virus growth. Journal of Virology. 2012; 86(19):10759-10765. 8. Bird, Brian H.; Dodd, Kimberly A.; Erickson, Bobbie Ray; Albarino, Cesar G.; Chakrabarti, Ayan K.; McMullan, Laura K.; Bergeron, Eric; Stroeher, Ute; Cannon, Deborah; Martin, Brock; Coleman-McCray, J. oann D.; Nichol, Stuart T., and Spiropoulou, Christina F. Severe hemorrhagic Fever in strain 13/n Guinea pigs infected with Lujo virus. PLoS Neglected Tropical Diseases. 2012; 6(8):e1801. 9. Bird, Brian H. Nichol Stuart T. Breaking the chain: Rift Valley fever virus control via livestock vaccination. Current Opinion in Virology. 2012; 2:1-9. 10. Blaney, D., J. Gee, and T. L. Smith. "Melioidosis Section in "Other Infectious Diseases Related to Travel"." CDC Health Information for International Travelers, (2012). 11. Bouley, A. J., H. M. Biggs, R. A. Stoddard, A. B. Morrissey, J. A. Bartlett, I. A. Afwamba, V. P. Maro, G. D. Kinabo, W. Saganda, S. Cleaveland, and J. A. Crump. "Brucellosis among Hospitalized Febrile Patients in Northern Tanzania." Am J Trop Med Hyg 87, no. 6 (2012): 1105-11. 12. Buzard GS, Baker D, Wolcott MJ, Norwood DA, Dauphin LA. 2012. Multi-platform comparison of ten commercial master mixes for probe-based real-time polymerase

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chain reaction detection of bioterrorism threat agents for surge preparedness. Forensic Sci Int. 2012 Nov 30; 223(1-3):292-7. 13. Carrington, M., U. Choe, S. Ubillos, D. Stanek, M. Campbell, L. Wansbrough, P. Lee, G. Churchwell, K. Rosas, S.R. Zaki, A. Hoffmaster, R. V. Tiller, and B. K. De. "Fatal Case of Brucellosis Misdiagnosed in Early Stages of Brucella Suis Infection in a 46- Year-Old Patient with Marfan Syndrome." Journal of clinical microbiology 50, no. 6 (2012): 2173 - 2175. 14. Carter, Stephen D.; Surtees, Rebecca; Walter, Cheryl T.; Ariza, Antonio; Bergeron, Eric; Nichol, Stuart T.; Hiscox, Julian A.; Edwards, Thomas A., and Barr, John N. Structure, function, and evolution of the Crimean-Congo hemorrhagic fever virus nucleocapsid protein. Journal of Virology. 2012; 86(20):10914-10923. 15. Centers for Disease Control and Prevention. Hantavirus pulmonary syndrome in visitors to a National Park - Yosemite Valley, California, 2012. Morbidity and Mortality Weekly Report. 2012; 61(46):952. 16. Centers for Disease Control and Prevention. Human exposures to marine Brucella isolated from a harbor porpoise-Maine, 2012. MMWR 61, no 25 (2012):461-63. 17. Chakraborty, A., SU. Khan, MA. Hasnat, S. Parveen, MS. Islam, A. Mikolon, RK. Chakraborty, B. Ahmed, K. Ara, N. Haider, S. Zaki, A Hoffmaster, M. Rahman, S. Luby, and MJ. Hossain. "Anthrax Outbreaks in Bangladesh, 2009 - 2010." Am J Trop Med Hyg 86, no. 4 (2012): 703-710. 18. Crabtree, Mary B.; Kent Crockett, Rebekah J.; Bird, Brian H.; Nichol, Stuart T.; Erickson, Bobbie Rae; Biggerstaff, Brad J.; Horiuchi, Kalanthe, and Miller, Barry R. Infection and Transmission of Rift Valley Fever Viruses Lacking the NSs and/or NSm Genes in Mosquitoes: Potential Role for NSm in Mosquito Infection. PLoS Neglected Tropical Diseases. 2012; 6(5):e1639. 19. Dauphin LA, Marston CK, Bhullar V, Baker D, Rahman M, Hossain MJ, Chakraborty A, Khan SU, Hoffmaster AR. 2012. Swab protocol for rapid laboratory diagnosis of cutaneous anthrax. J. Clin Microbiol. 2012 Dec; 50(12):3960-7. 20. De, B. K., and M. Guerra. "Brucellosis Section in "Other Infectious Diseases Related to Travel". In: Mosby E, Ed." CDC Health Information for International Travelers, (2012). 21. Dodd, Kimberly A.; Bird, Brian H.; Metcalfe, Maureen G.; Nichol, Stuart T., and Albarino, Cesar G. Single-Dose Immunization with Virus Replicon Particles Confers Rapid Robust Protection against Rift Valley Fever Virus Challenge. Journal of Virology. 2012; 86(8):4204-4212. 22. Duncan, C., Kersh, G.J., Spraker, T., Patyk, K.A., Fitzpatrick, K.A., Massung, R.F., Gelatt, T. (2012) Coxiella burnetii in Northern Fur Seal (Callorhinus ursinus) placentas from St. Paul Island, Alaska. J. Vector Borne and Zoonotic Diseases. 12(3):192-5. 23. Duncan, C., Savage. K., Williams. M., Dickerson, B., Kondas, A.V., Fitzpatrick, K.A., Guerrero, J.L., Spraker, T., Kersh. G.J. (2012) Multiple strains of Coxiella burnetii are

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present in the environment of St. Paul Island, Alaska. Transbound Emerg Dis. Jul 2. doi: 10.1111/j.1865-1682.2012.01353.x. 24. Ellis CK, Carroll DS, Lash RR, Peterson AT, Damon IK, Malekani J, Formenty P. Ecology and geography of human monkeypox case occurrences across Africa. J Wildl Dis. 2012 Apr; 48(2):335-47. 25. Eremeeva ME, Karpathy SE, Krueger L, Hayes EK, Williams AM, Zaldivar Y, Bennett S, Cummings R, Tilzer A, Velten RK, Kerr N, Dasch GA, Hu R. (2012) Two pathogens and one disease: detection and identification of flea-borne Rickettsiae in areas endemic for murine typhus in California. J Med Entomol. 49(6):1485-94. 26. Eremeeva ME, Berganza E, Suarez G, Gobern L, Dueger E, Castillo L, Reyes L, Wikswo ME, Abramowicz KF, Dasch GA, Lindblade KA. (2012) Investigation of an outbreak of rickettsial febrile illness in Guatemala, 2007. Int J Infect Dis. Dec 19. doi:pii: S1201-9712(12)01303-3. 10.1016/j.ijid.2012.11.011. 27. Gupta, Manisha; Macneil, Adam; Reed, Zachary D.; Rollin, Pierre E., and Spiropoulou, Christina F. Serology and cytokine profiles in patients infected with the newly discovered Bundibugyo ebolavirus. Virology. 2012; 423:119-124. 28. Higgins, James, Stuber, Todd, Christine Quance, William Edwards, Rebekah Tiller, Thomas Linfield, Jack Rhyan, Angela Berte, Beth Harris. Molecular epidemiology of Brucella abortus isolates from cattle, elk, and bison in the United States: 1998 - 2011. Appl Environ Micobiol 78, no 10 (2012):3674-84. 29. Hudson PN, Self J, Weiss S, Braden Z, Xiao Y, Girgis NM, Emerson G, Hughes C, Sammons SA, Isaacs SN, Damon IK, Olson VA. Elucidating the role of the complement control protein in monkeypox pathogenicity. PLoS One. 2012;7(4):e35086. doi:10.1371/journal.pone.0035086. Epub 2012 Apr 9. 30. Hughes CM, Newman FK, Davidson WB, Olson VA, Smith SK, Holman RC, Yan L,Frey SE, Belshe RB, Karem KL, Damon IK. Analysis of variola and vaccinia virus neutralization assays for smallpox vaccines. Clin Vaccine Immunol. 2012 Jul; 19(7):1116-8. doi: 10.1128/CVI.00056-12. 31. Juliao PC, Maslanka S, Dykes J, Gaul L, Bagdure S, Granzow-Kibiger L, Salehi E, Zink D, Neligan RP, Barton-Behravesh C, Lúquez, C, Biggerstaff M, Lynch M, Olson C, Williams I, and Barzilay EJ. 2012. National outbreak of type A foodborne botulism associated with a widely distributed commercially canned hot dog chili sauce. Clin Infect Dis. 2013 Feb; 56(3):376-82. doi: 10.1093/cid/cis901. Epub 2012 Oct 24. 32. Kato CY, Chung IH, Robinson LK, Austin AL, Dasch GA, Massung RF. (2013) Assessment of real-time PCR assay for detection of Rickettsia spp. and Rickettsia rickettsii in banked clinical samples. J. Clin. Microbiol. 51(1):314-7. doi: 10.1128/JCM.01723-12. Epub 2012 Nov 7. 33. Kersh GJ, Fitzpatrick KA, Self JS, Biggerstaff BJ, Massung RF. Long-Term Immune Responses to Coxiella burnetii after Vaccination. (2013) Clin Vaccine Immunol. 20(2):129-33.

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34. Kersh, G.J., Lambourn, D.M., Raverty, S.A., Fitzpatrick, K.A., Self, J.S., Akmajian, A.M., Jeffries, S.J., Huggins, J., Drew, C.P., Zaki, S.R., and Massung, R.F. (2012) Coxiella burnetii infection of Marine Mammals in the Pacific Northwest, 1997-2010. J. Wildlife Diseases. 48(1):201-206. 35. Kersh, G.J., Priestley, R.A., and Massung, R.F. (2012) Stability of Coxiella burnetii in stored human blood. Transfusion. Oct 3. doi: 10.1111/j.1537-2995.2012.03912.x. 36. Knust, Barbara; Medetov, Zhumagul B.; Kyraubayev, Kakimzhan B.; Bumburidi, Yekaterina; Erickson, Bobbie Rae; MacNeil, Adam; Nichol, Stuart T.; Baurzhan S. Bayserkin, and Ospanov, Kenes S. Crimean-Congo Hemorrhagic Fever, Kazakhstan, 2009-2010. Emerging Infectious Diseases. 2012; 18(4):643-645. 37. Lash RR, Carroll DS, Hughes CM, Nakazawa Y, Karem K, Damon IK, Peterson AT. Effects of georeferencing effort on mapping monkeypox case distributions and transmission risk. Int J Health Geogr. 2012 Jun 27;11:23. 38. Lederman ER, Davidson W, Groff HL, Smith SK, Warkentien T, Li Y, Wilkins KA, Karem KL, Akondy RS, Ahmed R, Frace M, Shieh WJ, Zaki S, Hruby DE, Painter WP, Bergman KL, Cohen JI, Damon IK. Progressive vaccinia: case description and laboratory-guided therapy with vaccinia immune globulin, ST-246, and CMX001. J Infect Dis. 2012 Nov; 206(9):1372-85. 39. Lipsitz, R., S. Garges, R. Aurigemma, P. Baccam, D. Blaney, J. Gee, J. Larsen, D. Limmathurotsakul, MG Morrow, R. Norton, E. O'Mara, S. J. Peacock, N. Pesik, LP Rogers, H. P. Schweizer, I. Steinmetz, G. Tan, P. Tan, WJ Wiersinga, V. Wuthiekanun, and TL. Smith. "Workshop on Treatment of and Postexposure Prophylaxis for Burkholderia Pseudomallei and B. Mallei Infection, 2010." Emerg Infect Dis 18, no. 12 (2012). 40. Lo, Michael K.; Lowe, Luis; Hummel, Kimberly B.; Sazzad, Hossain M. S.; Gurley, Emily S.; Hossain, M. Jahangir; Luby, Stephen P.; Miller, David M.; Comer, James A.; Rollin, Pierre E.; Bellini, William J., and Rota, Paul A. Characterization of Nipah Virus from Outbreaks in Bangladesh, 2008-2010. Emerging Infectious Diseases. 2012; 18(2):248-2. 41. Lo, Michael K.; Peeples, Mark E.; Bellini, William J.; Nichol, Stuart T.; Rota, Paul A., and Spiropoulou, Christina F. Distinct and overlapping roles of nipah virus P gene products in modulating the human endothelial cell antiviral response. PLoS One. 2012; 7(10):e47790. 42. Loehman, Rachel A.; Elias, Joran; Douglass, Richard J.; Kuenzi, Amy J.; Mills, James N., and Wagoner, Kent. Prediction of Peromyscus maniculatus (deer mouse) population dynamics in montana, USA, using satellite-driven vegetation productivity and weather data. Journal of Wildlife Diseases. 2012; 48(2):348-360. 43. Luis, Angela D.; Douglass, Richard J.; Hudson, Peter J.; Mills, James N., and Bjornstad, Ottar N. Sin Nombre hantavirus decreases survival of male deer mice. Oecologia. 2012; 169(2):431-439. 44. Lúquez C, Raphael BH, Joseph LA, Meno SR, Fernández, and Maslanka SE. 2012.

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Genetic diversity among Clostridium botulinum strains harboring bont/A2 and bont/A3 genes. App. Environ. Microbiol. 78: 8712 45. MacNeil, Adam and Rollin, Pierre E. Ebola and Marburg Hemorrhagic Fevers: Neglected Tropical Diseases? PLOS Neglected Tropical Diseases. 2012; 6(6):e1546. 46. Macneil, Adam; Stroher, Ute; Farnon, Eileen; Campbell, Shelley; Cannon, Deborah; Paddock, Christopher D.; Drew, Clifton P.; Kuehnert, Matthew; Knust, Barbara; Gruenenfelder, Robert; Zaki, Sherif R; Rollin, Pierre E., and Nichol, Stuart T. Solid Organ Transplant-associated Lymphocytic Choriomeningitis, United States, 2011. Emerging Infectious Diseases. 2012; 18(8):1256-1262. 47. Massung RF, Cutler SJ, Frangoulidis D. (2012) Molecular typing of Coxiella burnetii (Q fever). Adv Exp Med Biol. 984:381-96. 48. McCollum AM, Austin C, Nawrocki J, Howland J, Pryde J, Vaid A, Holmes D, Weil MR, Li Y, Wilkins K, Zhao H, Smith SK, Karem K, Reynolds MG, Damon IK. Investigation of the first laboratory-acquired human cowpox virus infection in the United States. J Infect Dis. 2012 Jul 1; 206(1):63-8. 49. McElroy, Anita K. and Nichol, Stuart T. Rift Valley fever virus inhibits a proinflammatory response in experimentally infected human monocyte derived macrophages and a pro-inflammatory cytokine response may be associated with patient survival during natural infection. Virology. 2012; 422(1):6-12. 50. McMullan, Laura K; Folk, Scott M.; Kelly, Aubree J.; MacNeil, Adam; Goldsmith, Cynthia S.; Metcalfe, Maureen G.; Batten, Brigid C.; Albarino, Cesar G.; Zaki, Sherif R.; Rollin, Pierre E.; Nicholson, William L., and Nichol, Stuart T. A new phlebovirus associated with severe febrile illness in Missouri. New England Journal of Medicine. 2012; 367(9):834-841. 51. McMullan, Laura K.; Frace, Mike; Sammons, Scott A.; Shoemaker, Trevor; Balinandi, Stephen; Wamala, Joseph F.; Lutwama, Julius J.; Downing, Robert G.; Stroeher, Ute; Macneil, Adam, and Nichol, Stuart T. Using next generation sequencing to identify yellow fever virus in Uganda. Virology. 2012; 422(1):1-5. 52. McNulty, Shanon; Flint, Michael; Nichol, Stuart T., and Spiropoulou, Christina F. Host mTORC1 Signaling Regulates Andes Virus Replication. Journal of Virology. 2012. 53. Meaney-Delman, D., ME Zotti, SA Rasmussen, S. Strasser, S. Shadomy, RM Turcios- Ruiz, GD Jr. Wendel, TA Treadwell, and DJ Jamieson. "Anthrax Cases in Pregnant and Postpartum Women: A Systematic Review." Obstet Gynecol 120, no. 6 (2012): 1439 - 49. 54. Memish, Ziad A.; Fagbo, Shamsudeen F.; Assiri, Abdullah M.; Rollin, Pierre; Zaki, Ali M.; Charrel, Remi; Mores, Chris, and MacNeil, Adam. Alkhurma Viral Hemorrhagic Fever Virus: Proposed Guidelines for Detection, Prevention, and Control in Saudi Arabia. PLOS Neglected Tropical Diseases. 2012; 6(7):e1604. 55. Mourya, Devendra T.; Yadav, Pragya D.; Shete, Anita M.; Gurav, Yogesh K.; Raut, Chandrashekhar G.; Jadi, Ramesh S.; Pawar, Shailesh D.; Nichol, Stuart T., and Mishra,

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Akhilesh C. Detection, isolation and confirmation of crimean-congo hemorrhagic Fever virus in human, ticks and animals in Ahmadabad, India, 2010-2011. PLoS Neglected Tropical Diseases. 2012; 6(5):e1653. 56. Palma, R. Eduardo; Polop, Jaime J.; Owen, Robert D., and Mills, James. N. Ecology of rodent-associated hantaviruses in the southern cone of South america: Argentina, Chile, Paraguay, and Uruguay. Journal of Wildlife Diseases. 2012; 48(2):267-281. 57. Price, E. P., J. L. Dale, J. M. Cook, D. S. Sarovich, M. L. Seymore, J. L. Ginther, E. L. Kaufman, S. M. Beckstrom-Sternberg, M. Mayo, M. Kaestli, M. B. Glass, J. E. Gee, V. Wuthiekanun, J. M. Warner, A. Baker, J. T. Foster, P. Tan, A. Tuanyok, D. Limmathurotsakul, S. J. Peacock, B. J. Currie, D. M. Rahman, Muhammad Aziz; Hossain, Mohammad Jahangir; Sultana, Sharmin; Homaira, Nusrat; Khan, Salah Uddin; Rahman, Mahmudur; Gurley, Emily S.; Rollin, Pierre E.; Lo, Michael K.; Comer, James A.; Lowe, Luis; Rota, Paul A.; Ksiazek, Thomas G.; Kenah, Eben; Sharker, Yushuf, and Luby, Stephen P. Date Palm Sap Linked to Nipah Virus Outbreak in Bangladesh, 2008. Vector Borne Zoonotic Diseases. 2012; 12(1):65-73. 58. Raphael BH, Lautenschlager M, Kalb S, de Jong LIT, Frace M, Lúquez C, Barr JR, Fernández, and Maslanka SE. 2012. Analysis of a unique Clostridium botulinum strain from the Southern hemisphere producing a novel type E botulinum neurotoxin subtype. BMC Micbiol. 12: 245 59. Raphael BH, Lautenschlager M, Kahler A, Pai S, Parks BA, Kalb SR, Maslanka SE, Shah S, Magnuson M, Hill VR. 2012. Ultrafiltration improves ELISA and Endopep MS analysis of botulinum neurotoxin type A in drinking water. J Microbiological Methods. 90: 267-272. 60. Raut, C. G.; Yadav, P. D.; Towner, Jonathan S.; Amman, Brian R.; Erickson, Bobbie Ray; Cannon, Deborah L.; Sivaram, A.; Basu, A.; Nichol, S. T.; Mishra, A. C., and Mourya, D. T. Isolation of a Novel Adenovirus from Rousettus leschenaultii Bats from India. Intervirology. 2012; 55(6):488-490. 61. Shoemaker, Trevor; MacNeil, Adam; Balinandi, Stephen; Campbell, Shelley; Wamala, Joseph Francis; McMullan, Laura K.; Downing, Robert; Lutwama, Julius; Mbidde, Edward; Ströher, Ute; Rollin, Pierre E., and Nichol, Stuart T. Reemerging Sudan Ebola Virus Disease in Uganda, 2011. Emerging Infectious Diseases. 2012; 18(9):1480-1483. 62. Smith, Darcy R.; Bird, Brian H.; Lewis, Bridget; Johnston, Sara C.; McCarthy, Sarah; Keeney, Ashley; Botto, Miriam; Donnelly, Ginger; Shamblin, Joshua; Albarino, Cesar G.; Nichol, Stuart T., and Hensley, Lisa E. Development of a novel nonhuman primate model for Rift Valley Fever. Journal of Virology. 2012; 86(4):2109-2120. 63. Wagner, P. Keim, and T. Pearson. "Development and Validation of Burkholderia Pseudomallei-Specific Real-Time Pcr Assays for Clinical, Environmental or Forensic Detection Applications." PLoS One 7, no. 5 (2012): e7723. 64. Wamala, Joseph F.; Malimbo, Mugagga; Okot, Charles L.; Atai-Omoruto, Ann D.; Tenywa, Emmanuel; Miller, Jeffrey R.; Balinandi, Stephen; Shoemaker, Trevor; Oyoo, Charles; Omony, Emmanuel O.; Kagirita, Atek; Musenero, Monica M.; Makumbi, Issa;

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Nanyunja, Miriam; Lutwama, Julius J.; Downing, Robert, and Mbonye, Anthony K. Epidemiological and laboratory characterization of a yellow fever outbreak in northern Uganda, October 2010-January 2011. International Journal of Infectious Diseases. 2012; 16(7):e536-4e52. 65. Wattam, Alice. R., Thomas. J. Inzana, Kelly P. Williams, Shriniwasrao P. Mane, Maulik Shukla, Nalvo F. Almeida, Allan W. Dickerman, Steven Mason, Ignacio Moriyon, David O'Callaghan, Adrian M. Whatmore, Bruno W. Sobral, Rebekah V. Tiller, Alex R. Hoffmaster, Michael A. Frace, Cristina De Castro, Antonio Molinaro, Stephen M. Boyle, Barun K. De, and Joao C. Setubal. "Comparative Genomics of Early-Diverging Brucella Strains Reveals a Novel Lipopolysaccharide Biosynthesis Pathway." mBio - ASM 3, no. 5 (2012): 1 - 11. 66. Yadav, Pragya D.; Raut, Chandrashekhar G.; Shete, Anita M.; Mishra, Akhilesh C.; Towner, Jonathan S.; Nichol, Stuart T., and Mourya, Devendra T. Detection of Nipah Virus RNA in Fruit Bat (Pteropus giganteus) from India. American Journal of Tropical Medicine and Hygiene. 2012; 87(3):576-578. 67. Zeng H, Goldsmith CS, Maines TR, Belser JA, Gustin KM, Pekosz A, Zaki SR, Katz JM, Tumpey TM Tropism and Infectivity of Influenza Virus, Including Highly Pathogenic Avian H5N1 Virus, in Ferret Tracheal Differentiated Primary Epithelial Cell Cultures.. J Virol. 2013 Mar;87(5):2597-607. doi: 10.1128/JVI.02885-12. Epub 2012 Dec 19. 68. Ledgerwood JE, Hu Z, Gordon IJ, Yamshchikov G, Enama ME, Plummer S, Bailer R, Pearce MB, Tumpey TM, Koup RA, Mascola JR, Nabel GJ, Graham BS Influenza virus h5 DNA vaccination is immunogenic by intramuscular and intradermal routes in humans.; VRC 304 and VRC 305 Study Teams. Clin Vaccine Immunol. 2012 Nov; 19(11):1792-7. doi: 10.1128/CVI.05663-11. 69. Uyeki TM, Nguyen DC, Rowe T, Lu X, Hu-Primmer J, Huynh LP, Hang NL, Katz JM. Seroprevalence of antibodies to avian influenza A (H5) and A (H9) viruses among market poultry workers, Hanoi, Vietnam, 2001. PLoS One. 2012;7(8):e43948. doi: 10.1371/journal.pone.0043948. 70. Nguyen T, Rivailler P, Davis CT, Hoa do T, Balish A, Dang NH, Jones J, Vui DT, Simpson N, Huong NT, Shu B, Loughlin R, Ferdinand K, Lindstrom SE, York IA, Klimov A, Donis RO. Evolution of highly pathogenic avian influenza (H5N1) virus populations in Vietnam between 2007 and 2010. Virology. 2012 Oct 25; 432(2):405-16. doi: 10.1016/j.virol.2012.06.021. 71. Kosasih H, Roselinda, Nurhayati, Klimov A, Xiyan X, Lindstrom S, Mahoney F, Beckett C, Burgess TH, Blair PJ, Uyeki TM, Sedyaningsih ER. Surveillance of Influenza in Indonesia, 2003-2007. Influenza Other Respi Viruses. 2012 Jul 13. doi: 10.1111/j.1750-2659.2012.00403.x. 72. Ostrowsky B, Huang A, Terry W, Anton D, Brunagel B, Traynor L, Abid S, Johnson G, Kacica M, Katz J, Edwards L, Lindstrom S, Klimov A, Uyeki TM Low pathogenic avian influenza A (H7N2) virus infection in immunocompromised adult, New York,

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USA, 2003.. Emerg Infect Dis. 2012 Jul;18(7):1128-31. doi: 10.3201/eid1807.111913. 73. Sorn S, Sok T, Ly S, Rith S, Tung N, Viari A, Gavotte L, Holl D, Seng H, Asgari N, Richner B, Laurent D, Chea N, Duong V, Toyoda T, Yasuda CY, Kitsutani P, Zhou P, Bing S, Deubel V, Donis R, Frutos R, Buchy PDynamic of H5N1 virus in Cambodia and emergence of a novel endemic sub-clade.. Infect Genet Evol. 2012 Jun 7. 74. Yang H, Carney PJ, Donis RO, Stevens J. Structure and receptor complexes of the hemagglutinin from a highly pathogenic H7N7 influenza virus. J Virol. 2012 Aug; 86(16):8645-52. doi: 10.1128/JVI.00281-12. 75. Kwon D, Lee JY, Choi W, Choi JH, Chung YS, Lee NJ, Cheong HM, Katz JM, Oh HB, Cho H, Kang C. Avian influenza a (H5N1) virus antibodies in poultry cullers, South Korea, 2003-2004. Emerg Infect Dis. 2012 Jun;18(6):986-8. doi: 10.3201/eid1806.111631. 76. Pearce MB, Belser JA, Gustin KM, Pappas C, Houser KV, Sun X, Maines TR, Pantin- Jackwood MJ, Katz JM, Tumpey TM. Seasonal trivalent inactivated influenza vaccine protects against 1918 Spanish influenza virus infection in ferrets. J Virol. 2012 Jul; 86(13):7118-25. doi: 10.1128/JVI.00674-12. 77. Kim YC, Song JM, Lipatov AS, Choi SO, Lee JW, Donis RO, Compans RW, Kang SM, Prausnitz MR. Increased immunogenicity of avian influenza DNA vaccine delivered to the skin using a microneedle patch. Eur J Pharm Biopharm. 2012 Jun; 81(2):239-47. doi: 10.1016/j.ejpb.2012.03.010. 78. De Marco D, Clementi N, Mancini N, Solforosi L, Moreno GJ, Sun X, Tumpey TM, Gubareva LV, Mishin V, Clementi M, Burioni R. A non-VH1-69 heterosubtypic neutralizing human monoclonal antibody protects mice against H1N1 and H5N1 viruses. PLoS One. 2012; 7(4):e34415. doi: 10.1371/journal.pone.0034415. 79. Pandey A, Singh N, Vemula SV, Couëtil L, Katz JM, Donis R, Sambhara S, Mittal SK. Impact of preexisting adenovirus vector immunity on immunogenicity and protection conferred with an adenovirus-based H5N1 influenza vaccine. PLoS One. 2012; 7(3):e33428. doi: 10.1371/journal.pone.0033428. 80. Belser JA, Gustin KM, Maines TR, Pantin-Jackwood MJ, Katz JM, Tumpey TM. Influenza virus respiratory infection and transmission following ocular inoculation in ferrets. PLoS Pathog. 2012;8(3):e1002569. doi: 10.1371/journal.ppat.1002569. 81. Murray JL, McDonald NJ, Sheng J, Shaw MW, Hodge TW, Rubin DH, O'Brien WA, Smee DF. Inhibition of influenza A virus replication by antagonism of a PI3K-AKT- mTOR pathway member identified by gene-trap insertional mutagenesis. Antivir Chem Chemother. 2012 May 14; 22(5):205-15. doi: 10.3851/IMP2080. 82. Schat KA, Bingham J, Butler JM, Chen LM, Lowther S, Crowley TM, Moore RJ, Donis RO, Lowenthal JW. Role of position 627 of PB2 and the multibasic cleavage site of the hemagglutinin in the virulence of H5N1 avian influenza virus in chickens and ducks. PLoS One. 2012; 7(2):e30960. doi: 10.1371/journal.pone.0030960. 83. Fouchier RA, García-Sastre A, Kawaoka Y, Barclay WS, Bouvier NM, Brown IH,

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Capua I, Chen H, Compans RW, Couch RB, Cox NJ, Doherty PC, Donis RO, Feldmann H, Guan Y, Katz J, Klenk HD, Kobinger G, Liu J, Liu X, Lowen A, Mettenleiter TC, Osterhaus AD, Palese P, Peiris JS, Perez DR, Richt JA, Schultz-Cherry S, Steel J, Subbarao K, Swayne DE, Takimoto T, Tashiro M, Taubenberger JK, Thomas PG, Tripp RA, Tumpey TM, Webby RJ, Webster RG. Pause on avian flu transmission research. Science. 2012 Jan 27; 335(6067):400-1. doi: 10.1126/science.335.6067.400. 84. Cilloniz C, Pantin-Jackwood MJ, Ni C, Carter VS, Korth MJ, Swayne DE, Tumpey TM, Katze MG.Molecular signatures associated with Mx1-mediated resistance to highly pathogenic influenza virus infection: mechanisms of survival. J Virol. 2012 Mar; 86(5):2437-46. doi: 10.1128/JVI.06156-11. 85. Maines TR, Belser JA, Gustin KM, van Hoeven N, Zeng H, Svitek N, von Messling V, Katz JM, Tumpey TM.Local innate immune responses and influenza virus transmission and virulence in ferrets. J Infect Dis. 2012 Feb 1; 205(3):474-85. doi: 10.1093/infdis/jir768. 86. Belser JA, Sleeman K, Pearce MB, Katz JM, Gubareva LV, Tumpey TM.Oseltamivir inhibits H7 influenza virus replication in mice inoculated by the ocular route. Antimicrob Agents Chemother. 2012 Mar; 56(3):1616-8. doi: 10.1128/AAC.06101-11. 87. Giles BM, Bissel SJ, Craigo JK, Dealmeida DR, Wiley CA, Tumpey TM, Ross TM. Elicitation of anti-1918 influenza virus immunity early in life prevents morbidity and lower levels of lung infection by 2009 pandemic H1N1 influenza virus in aged mice. J Virol. 2012 Feb; 86(3):1500-13. doi: 10.1128/JVI.06034-11. 88. Dong L, Liu F, Fairman J, Hong DK, Lewis DB, Monath T, Warner JF, Belser JA, Patel J, Hancock K, Katz JM, Lu X.Cationic liposome-DNA complexes (CLDC) adjuvant enhances the immunogenicity and cross-protective efficacy of a pre-pandemic influenza A H5N1 vaccine in mice. Vaccine. 2012 Jan 5; 30(2):254-64. doi: 10.1016/j.vaccine.2011.10.103. 89. Chittaganpitch M, Supawat K, Olsen SJ, Waicharoen S, Patthamadilok S, Yingyong T, Brammer L, Epperson SP, Akrasewi P, Sawanpanyalert P.Influenza viruses in Thailand: 7 years of sentinel surveillance data, 2004-2010. Influenza Other Respi Viruses. 2012 Jul; 6(4):276-83. doi: 10.1111/j.1750-2659.2011.00302.x. 90. Zeng H, Pappas C, Belser JA, Houser KV, Zhong W, Wadford DA, Stevens T, Balczon R, Katz JM, Tumpey TM.Human pulmonary microvascular endothelial cells support productive replication of highly pathogenic avian influenza viruses: possible involvement in the pathogenesis of human H5N1 virus infection. J Virol. 2012 Jan; 86(2):667-78. doi: 10.1128/JVI.06348-11. 91. Chen LM, Blixt O, Stevens J, Lipatov AS, Davis CT, Collins BE, Cox NJ, Paulson JC, Donis RO. In vitro evolution of H5N1 avian influenza virus toward human-type receptor specificity. Virology. 2012 Jan 5;422(1):105-13. doi: 10.1016/j.virol.2011.10.006. 92. Gambaryan AS, Lomakina NF, Boravleva EY, Kropotkina EA, Mashin VV, Krasilnikov IV, Klimov AI, Rudenko LG. Comparative safety, immunogenicity, and

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efficacy of several anti-H5N1 influenza experimental vaccines in a mouse and chicken models (Testing of killed and live H5 vaccine). Influenza Other Respi Viruses. 2012 May; 6(3):188-95. doi:10.1111/j.1750-2659.2011.00291.x.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: Activities include developing diagnostic assays for public health, conducting molecular and antigenic characterization of organisms, determing pathogenictiy and virulence of infectious agents, determining the natural history of infectious organisms, and conducting epidemiologic studies and surveillance for diseases.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A, B and C Priority Pathogens

• Overlap Select Agents Including NIAID Category A, B and C Priority Pathogens

• USDA Select Agents and Toxins • Other pathogens or toxins

(iii) Outdoor Studies: None

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Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

CDC, OID, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Vector Borne Diseases (DVBD) - Ft. Collins

2. Where is it located (provide both address and geographical location)?

Centers for Disease Control and Prevention, U.S. Department of Health and Human Services 3150 Rampart Road Fort Collins, Colorado 80521

3. Floor area of laboratory areas by containment level:

BL2 66 (sqM) BL3 1142 (sqM) BL4 0 (sqM) Total laboratory floor area 1208 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 53

(ii) Division of personnel:

Military 0

Civilian 53

(iii) Division of personnel by category:

Scientists 44

Engineers 0

Technicians 4

Administrative and support staff 5

(iv) List the scientific disciplines represented in the scientific/engineering staff.

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Biology, Ecology, Epidemiology, General Engineering, Medicine, Microbiology, Molecular Biology, Public Health, Statistics, Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 15

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

Centers for Disease Control and Prevention (CDC)

(vii) What are the funding levels for the following program areas:

Research $ 780,716 Development $ 780,716 Test and evaluation $ 745,580 Total $ 2,307,012

(viii) Briefly describe the publication policy of the facility:

Publication is encouraged and managed by editorial and clearance policies conducted at all levels of the Agency.

The clearance policy for information products disseminated outside CDC for public use is available online at: http://www.cdc.gov/od/science/policies

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

1. Borchert JN, Eisen RJ, Atiku LA, Delorey MJ, Mpanga JT, Babi N, Enscore RE, Gage KL. Efficacy of indoor residual spraying using lambda-cyhalothrin for controlling nontarget vector fleas (Siphonaptera) on commensal rats in a plague endemic region of northwestern Uganda. J Med Entomol. 2012 Sep; 49(5):1027-34.

2. Borchert JN, Eisen RJ, Holmes JL, Atiku LA, Mpanga JT, Brown HE, Graham CB, Babi N, Montenieri JA, Enscore RE, Gage KL. Evaluation and modification of off-host flea collection techniques used in northwest Uganda: laboratory and field studies. J Med Entomol. 2012 Jan; 49(1):210-4. 3. Chiou SS, Fan YC, Crill WD, Chang RY, Chang GJ. Mutation analysis of the cross-

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reactive epitopes of Japanese encephalitis virus envelope glycoprotein. J Gen Virol. 2012 Jun; 93(Pt 6):1185-92. 4. Crabtree MB, Kent Crockett RJ, Bird BH, Nichol ST, Erickson BR, Biggerstaff BJ, Horiuchi K, Miller BR. Infection and transmission of Rift Valley fever viruses lacking the NSs and/or NSm genes in mosquitoes: potential role for NSm in mosquito infection. PLoS Negl Trop Dis. 2012 May; 6(5):e1639. 5. Eisen RJ, Borchert JN, Mpanga JT, Atiku LA, MacMillan K, Boegler KA, Montenieri JA, Monaghan A, Gage KL. Flea diversity as an element for persistence of plague bacteria in an East African plague focus. PLoS One. 2012; 7(4):e35598. 6. Gage KL. Factors affecting the spread and maintenance of plague. Adv Exp Med Biol. 2012; 954:79-94. Review. 7. Graham CB, Black WC, Boegler KA, Montenieri JA, Holmes JL, Gage KL, Eisen RJ. Combining real-time polymerase chain reaction using SYBR Breen I detection and sequencing to identify vertebrate blood meals in fleas. J Med Entomol. 2012 Nov; 49(6):1442-52 8. Graham CB, Borchert JN, Black WC 4th, Atiku LA, Mpanga JT, Boegler KA, Moore SM, Gage KL, Eisen RJ. Blood Meal Identification in Off-Host Cat Fleas (Ctenocephalides felis) from a Plague-Endemic Region of Uganda. Am J Trop Med Hyg. Epub 2012 Dec 3. 9. Jones RT, Bernhardt SA, Martin AP, Gage KL. Interactions among symbionts of Oropsylla spp. (Siphonoptera: Ceratophyllidae). J Med Entomol. 2012 May; 49(3):492- 6. 10. Jones RT, Vetter SM, Montenieiri J, Holmes J, Bernhardt SA, Gage KL. Yersinia pestis infection and laboratory conditions alter flea-associated bacterial communities. ISME J. 2012 Aug 16. doi: 10.1038/ismej.2012.95. 11. MacMillan K, Monaghan AJ, Apangu T, Griffith KS, Mead PS, Acayo S, Acidri R, Moore SM, Mpanga JT, Enscore RE, Gage KL, Eisen RJ. Climate predictors of the spatial distribution of human plague cases in the West Nile region of Uganda. Am J Trop Med Hyg. 2012 Mar; 86(3):514-23. 12. Moore SM, Monaghan A, Griffith KS, Apangu T, Mead PS, Eisen RJ. Improvement of Disease Prediction and Modeling through the Use of Meteorological Ensembles: Human Plague in Uganda. PLoS One. 2012; 7(9):e44431. 13. Schotthoefer AM, Eisen RJ, Kugeler KJ, Ettestad P, Reynolds PJ, Brown T, Enscore RE, Cheek J, Bueno R Jr, Targhetta J, Montenieri JA, Gage KL. Changing socioeconomic indicators of human plague, New Mexico, USA. Emerg Infect Dis. 2012 Jul; 18(7):1151-4. doi: 10.3201/eid1807.120121. 14. Urich SK, Chalcraft L, Schriefer ME, Yockey BM, Petersen JM. Lack of antimicrobial resistance in Yersinia pestis isolates from 17 countries in the Americas, Africa, and Asia. Antimicrob Agents Chemother. 2012 Jan; 56(1):555-8. 15. Woolpert T, Staples JE, Faix DJ, Nett RJ, Kosoy OI, Biggerstaff BJ, Johnson BW,

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Sracic M, Fischer M. Immunogenicity of one dose of Vero cell culture-derived Japanese encephalitis (JE) vaccine in adults previously vaccinated with mouse brain- derived JE vaccine. Vaccine. 2012 Apr 26; 30(20):3090-6.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: CDC's Division of Vector Borne Diseases (DVBD) possesses many of the select agents that are on the Department of Health and Human Services (HHS) and HHS/U.S. Department of Agriculture overlap lists. Within CDC, DVBD has the primary responsibility for research on tularemia, plague and the alphaviruses. This research involves development of assays for surveillance and detection of each agent and molecular and antigenic characterization.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins

Including NIAID Category A and B Priority Pathogens

• Overlap Select Agents Including NIAID Category B Priority Pathogens

• Other pathogens or toxins Including non-Select Agent, NIAID Category B and C Priority Pathogens

(iii) Outdoor Studies: None

Page 136 of 237

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Integrated Research Facility (IRF) - Rocky Mountain Laboratories (RML)

2. Where is it located (provide both address and geographical location)?

903 South 4th Street Hamilton, Montana 59840

3. Floor area of laboratory areas by containment level:

BL2 1361 (sqM) BL3 407 (sqM) BL4 1145 (sqM) Total laboratory floor area 2913 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 96

(ii) Division of personnel:

Military 0

Civilian 96

(iii) Division of personnel by category:

Scientists 70

Engineers 0

Technicians 23

Administrative and support staff 3

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Bacteriology, Biology, Chemistry, Immunology, Medicine, Microbiology, Molecular Biology, Parasitology, Pathogenesis, Prionology, Rickettsiology, Toxicology, Vaccine Evaluation, Virology

Page 137 of 237

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 2

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Health and Human Services (HHS)

(vii) What are the funding levels for the following program areas:

Research $ 24,752,010 Development $ 0 Test and evaluation $ 0 Total $ 24,752,010

(viii) Briefly describe the publication policy of the facility:

All researchers are encouraged to publish results in peer-reviewed open literature. The NIH Public Access Policy (http://publicaccess.nih.gov/policy.htm) ensures that the public has access to the published results of NIH funded research. It requires scientists to submit final peer-reviewed journal manuscripts that arise from NIH funds to the National Library of Medicine's digital archive PubMed Central (http://www.ncbi.nlm.nih.gov/pmc/) upon acceptance for publication. To help advance science and improve human health, the policy requires that these papers are accessible to the public on PubMed Central no later than 12 months after publication.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

1. Baker DG, Woods TA, Butchi NB, Morgan TM, Taylor RT, Sunyakumthorn P, Mukherjee P, Lubick KJ, Best SM, Peterson KE. Toll-like receptor 7 suppresses virus replication in neurons but does not affect viral pathogenesis in a mouse model of Langat virus infection. J Gen Virol. 2013 Feb; 94(Pt 2):336-47. doi: 10.1099/vir.0.043984-0. Epub 2012 Nov 7. PubMed PMID: 23136362.

2. Beare PA, Larson CL, Gilk SD, Heinzen RA. Two systems for targeted gene deletion in Coxiella burnetii. Appl Environ Microbiol. 2012 Jul; 78(13):4580-9. doi: 10.1128/AEM.00881-12. Epub 2012 Apr 20. PubMed PMID: 22522687; PubMed Central PMCID: PMC3370473.

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3. Bessen RA, Wilham JM, Lowe D, Watschke CP, Shearin H, Martinka S, Caughey B, Wiley JA. Accelerated shedding of prions following damage to the olfactory epithelium. J Virol. 2012 Feb; 86(3):1777-88. doi: 10.1128/JVI.06626-11. Epub 2011 Nov 30. PubMed PMID: 22130543; PubMed Central PMCID: PMC3264367. 4. Bosio CF, Jarrett CO, Gardner D, Hinnebusch BJ. Kinetics of innate immune response to Yersinia pestis after intradermal infection in a mouse model. Infect Immun. 2012 Nov; 80(11):4034-45. doi: 10.1128/IAI.00606-12. Epub 2012 Sep 10. PubMed PMID: 22966041; PubMed Central PMCID: PMC3486050. 5. Bossart KN, Rockx B, Feldmann F, Brining D, Scott D, LaCasse R, Geisbert JB, Feng YR, Chan YP, Hickey AC, Broder CC, Feldmann H, Geisbert TW. A Hendra virus G glycoprotein subunit vaccine protects African green monkeys from Nipah virus challenge. Sci Transl Med. 2012 Aug 8; 4(146):146ra107. doi: 10.1126/scitranslmed.3004241. PubMed PMID: 22875827; PubMed Central PMCID: PMC3516289. 6. Brown KS, Ebihara H, Feldmann H. Development of a minigenome system for Andes virus, a New World hantavirus. Arch Virol. 2012 Nov; 157(11):2227-33. doi: 10.1007/s00705-012-1401-0. Epub 2012 Jul 21. PubMed PMID: 22821183; PubMed Central PMCID: PMC3517727. 7. Celli J. LRSAM1, an E3 Ubiquitin ligase with a sense for bacteria. Cell Host Microbe. 2012 Dec 13; 12(6):735-6. doi: 10.1016/j.chom.2012.11.007. PubMed PMID: 23245317. 8. Chianini F, Fernández-Borges N, Vidal E, Gibbard L, Pintado B, de Castro J, Priola SA, Hamilton S, Eaton SL, Finlayson J, Pang Y, Steele P, Reid HW, Dagleish MP, Castilla J. Rabbits are not resistant to prion infection. Proc Natl Acad Sci U S A. 2012 Mar 27; 109(13):5080-5. doi: 10.1073/pnas.1120076109. Epub 2012 Mar13. PubMed PMID: 22416127; PubMed Central PMCID: PMC3323982. 9. Chong A, Wehrly TD, Child R, Hansen B, Hwang S, Virgin HW, Celli J. Cytosolic clearance of replication-deficient mutants reveals Francisella tularensis interactions with the autophagic pathway. Autophagy. 2012 Sep; 8(9):1342-56. doi:10.4161/auto.20808. Epub 2012 Aug 6. PubMed PMID: 22863802; PubMed Central PMCID:PMC3442881. 10. Chouikha I, Hinnebusch BJ. Yersinia--flea interactions and the evolution of the arthropod-borne transmission route of plague. Curr Opin Microbiol. 2012Jun; 15(3):239-46. doi: 10.1016/j.mib.2012.02.003. Epub 2012 Mar 7. Review. PubMed PMID: 22406208; PubMed Central PMCID: PMC3386424. 11. Crane DD, Scott DP, Bosio CM. Generation of a convalescent model of virulent Francisella tularensis infection for assessment of host requirements for survival of tularemia. PLoS One. 2012; 7(3):e33349. doi: 10.1371/journal.pone.0033349. Epub 2012 Mar 12. PubMed PMID: 22428026; PubMed Central PMCID: PMC3299770. 12. De Pascalis R, Chou AY, Bosio CM, Huang CY, Follmann DA, Elkins KL. Development of functional and molecular correlates of vaccine-induced protection for a

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model intracellular pathogen, F. tularensis LVS. PLoS Pathog. 2012 Jan;8(1):e1002494. doi: 10.1371/journal.ppat.1002494. Epub 2012 Jan 19. PubMed PMID: 22275868; PubMed Central PMCID: PMC3262015. 13. Ebihara H, Zivcec M, Gardner D, Falzarano D, Lacasse R, Rosenke R, Long D, Haddock E, Fischer E, Kawaoka Y, Feldmann H. A Syrian golden hamster model recapitulating ebola hemorrhagic Fever. J Infect Dis. 2013 Jan; 207(2):306-18. doi: 10.1093/infdis/jis626. Epub 2012 Oct 8. PubMed PMID: 23045629; PubMed Central PMCID: PMC3532827. 14. Fouchier RA, García-Sastre A, Kawaoka Y, Barclay WS, Bouvier NM, Brown IH, Capua I, Chen H, Compans RW, Couch RB, Cox NJ, Doherty PC, Donis RO, Feldmann H,Guan Y, Katz J, Klenk HD, Kobinger G, Liu J, Liu X, Lowen A, Mettenleiter TC, Osterhaus AD, Palese P, Peiris JS, Perez DR, Richt JA, Schultz-Cherry S, Steel J, Subbarao K, Swayne DE, Takimoto T, Tashiro M, Taubenberger JK, Thomas PG, Tripp RA, Tumpey TM, Webby RJ, Webster RG. Pause on avian flu transmission research. Science. 2012 Jan 27; 335(6067):400-1. doi: 10.1126/science.335.6067.400. PubMed PMID: 22282787. 15. Geisbert TW, Feldmann H, Broder CC. Animal challenge models of henipavirus infection and pathogenesis. Curr Top Microbiol Immunol. 2012; 359:153-77. doi: 10.1007/82_2012_208. Review. PubMed PMID: 22476556. 16. Ghigo E, Colombo MI, Heinzen RA. The Coxiella burnetii parasitophorous vacuole. Adv Exp Med Biol. 2012; 984:141-69. doi: 10.1007/978-94-007-4315-1_8. Review. PubMed PMID: 22711631. 17. Go JT, Belisle SE, Tchitchek N, Tumpey TM, Ma W, Richt JA, Safronetz D, Feldmann H, Katze MG. 2009 pandemic H1N1 influenza virus elicits similar clinical course but differential host transcriptional response in mouse, macaque, and swine infection models. BMC Genomics. 2012 Nov 15; 13:627. doi: 10.1186/1471-2164-13-627. PubMed PMID: 23153050; PubMed Central PMCID: PMC3532173. 18. Graves SF, Kobayashi SD, Braughton KR, Whitney AR, Sturdevant DE, Rasmussen DL, Kirpotina LN, Quinn MT, DeLeo FR. Sublytic concentrations of Staphylococcus aureus Panton-Valentine leukocidin alter human PMN gene expression and enhance bactericidal capacity. J Leukoc Biol. 2012 Aug; 92(2):361-74. doi: 10.1189/jlb.1111575. Epub 2012 May 11. PubMed PMID: 22581932; PubMed Central PMCID: PMC3395418. 19. Greub G, Gikas A, Heinzen RA, Dumler JS. Rickettsia and other intracellular bacteria: recent outbreaks, novel pathogens, emerging diseases, new tools, and outstanding discoveries. FEMS Immunol Med Microbiol. 2012 Feb; 64(1):1-2. doi: 10.1111/j.1574- 695X.2011.00915.x. Epub 2011 Dec 12. PubMed PMID: 22118608. 20. Grolla A, Mehedi M, Lindsay R, Bosio C, Duse A, Feldmann H. Enhanced detection of Rift Valley fever virus using molecular assays on whole blood samples. J Clin Virol. 2012 Aug; 54(4):313-7. doi: 10.1016/j.jcv.2012.04.022. Epub 2012 May 24. PubMed PMID: 22632901; PubMed Central PMCID: PMC3398164.

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21. Groseth A, Marzi A, Hoenen T, Herwig A, Gardner D, Becker S, Ebihara H, Feldmann H. The Ebola virus glycoprotein contributes to but is not sufficient for virulence in vivo. PLoS Pathog. 2012; 8(8):e1002847. doi: 10.1371/journal.ppat.1002847. Epub 2012 Aug 2. PubMed PMID: 22876185; PubMed Central PMCID: PMC3410889. 22. Hasebe R, Raymond GJ, Horiuchi M, Caughey B. Reaction of complement factors varies with prion strains in vitro and in vivo. Virology. 2012 Feb 20; 423(2):205-13. doi: 10.1016/j.virol.2011.11.017. Epub 2012 Jan 3. PubMed PMID: 22222213; PubMed Central PMCID: PMC3275752. 23. Hinnebusch BJ. Biofilm-dependent and biofilm-independent mechanisms of transmission of Yersinia pestis by fleas. Adv Exp Med Biol. 2012; 954:237-43. doi: 10.1007/978-1-4614-3561-7_30. Review. PubMed PMID: 22782769. 24. Hoenen T, Groseth A, Feldmann H. Current ebola vaccines. Expert Opin Biol Ther. 2012 Jul; 12(7):859-72. doi: 10.1517/14712598.2012.685152. Epub 2012 May 5. Review. PubMed PMID: 22559078; PubMed Central PMCID: PMC3422127. 25. Hoenen T, Shabman RS, Groseth A, Herwig A, Weber M, Schudt G, Dolnik O, BaslerCF, Becker S, Feldmann H. Inclusion bodies are a site of ebolavirus replication. J Virol. 2012 Nov; 86(21):11779-88. doi: 10.1128/JVI.01525-12. Epub 2012 Aug 22. PubMed PMID: 22915810; PubMed Central PMCID: PMC3486333. 26. Huang Q, Deng X, Best SM, Bloom ME, Li Y, Qiu J. Internal polyadenylation of parvoviral precursor mRNA limits progeny virus production. Virology. 2012 May 10; 426(2):167-77. doi: 10.1016/j.virol.2012.01.031. Epub 2012 Feb 21. PubMed PMID: 22361476; PubMed Central PMCID: PMC3294060. 27. Ippolito G, Feldmann H, Lanini S, Vairo F, Di Caro A, Capobianchi MR, Nicastri E. Viral hemorrhagic fevers: advancing the level of treatment. BMC Med. 2012 Mar 29; 10:31. doi: 10.1186/1741-7015-10-31. Review. PubMed PMID: 22458265; PubMed Central PMCID: PMC3325866. 28. Jiwani S, Ohr RJ, Fischer ER, Hackstadt T, Alvarado S, Romero A, Jewett TJ. Chlamydia trachomatis Tarp cooperates with the Arp2/3 complex to increase the rate of actin polymerization. Biochem Biophys Res Commun. 2012 Apr 20; 420(4):816-21. doi: 10.1016/j.bbrc.2012.03.080. Epub 2012 Mar 23. PubMed PMID: 22465117; PubMed Central PMCID: PMC3334425. 29. Kajihara M, Marzi A, Nakayama E, Noda T, Kuroda M, Manzoor R, Matsuno K, Feldmann H, Yoshida R, Kawaoka Y, Takada A. Inhibition of Marburg virus budding by nonneutralizing antibodies to the envelope glycoprotein. J Virol. 2012 Dec; 86(24):13467-74. doi: 10.1128/JVI.01896-12. Epub 2012 Oct 3. PubMed PMID: 23035224; PubMed Central PMCID: PMC3503067. 30. Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2012 Apr; 8(4):445-544. PubMed PMID: 22966490; PubMed Central PMCID: PMC3404883. 31. Kobayashi SD, DeLeo FR. Inflammation in 3D. Cell Host Microbe. 2012 Jun 14;

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10.1371/journal.pntd.0001923. Epub 2012 Dec 6. PubMed PMID: 23236527; PubMed Central PMCID: PMC3516577. 42. Marzi A, Yoshida R, Miyamoto H, Ishijima M, Suzuki Y, Higuchi M, Matsuyama Y, Igarashi M, Nakayama E, Kuroda M, Saijo M, Feldmann F, Brining D, Feldmann H, Takada A. Protective efficacy of neutralizing monoclonal antibodies in a nonhuman primate model of Ebola hemorrhagic fever. PLoS One. 2012; 7(4):e36192. doi: 10.1371/journal.pone.0036192. Epub 2012 Apr 27. PubMed PMID: 22558378; PubMed Central PMCID: PMC3338609. 43. McGuire LI, Peden AH, Orrú CD, Wilham JM, Appleford NE, Mallinson G, Andrews M, Head MW, Caughey B, Will RG, Knight RS, Green AJ. Real time quaking-induced conversion analysis of cerebrospinal fluid in sporadic Creutzfeldt-Jakob disease. Ann Neurol. 2012 Aug; 72(2):278-85. doi: 10.1002/ana.23589. PubMed PMID: 22926858; PubMed Central PMCID: PMC3458796. 44. McNally KL, Mitzel DN, Anderson JM, Ribeiro JM, Valenzuela JG, Myers TG, Godinez A, Wolfinbarger JB, Best SM, Bloom ME. Differential salivary gland transcript expression profile in Ixodes scapularis nymphs upon feeding or flavivirus infection. Ticks Tick Borne Dis. 2012 Feb; 3(1):18-26. doi: 10.1016/j.ttbdis.2011.09.003. Epub 2012 Jan 2. PubMed PMID: 22309855; PubMed Central PMCID: PMC3275779. 45. Mire CE, Miller AD, Carville A, Westmoreland SV, Geisbert JB, Mansfield KG, Feldmann H, Hensley LE, Geisbert TW. Recombinant vesicular stomatitis virus vaccine vectors expressing filovirus glycoproteins lack neurovirulence in nonhuman primates. PLoS Negl Trop Dis. 2012; 6(3):e1567. doi: 10.1371/journal.pntd.0001567. Epub 2012 Mar 20. PubMed PMID: 22448291; PubMed Central PMCID: PMC3308941. 46. Munster VJ, Prescott JB, Bushmaker T, Long D, Rosenke R, Thomas T, Scott D, Fischer ER, Feldmann H, de Wit E. Rapid Nipah virus entry into the central nervous system of hamsters via the olfactory route. Sci Rep. 2012; 2:736. doi: 10.1038/srep00736. Epub 2012 Oct 15. PubMed PMID: 23071900; PubMed Central PMCID: PMC3471094. 47. Offerdahl DK, Dorward DW, Hansen BT, Bloom ME. A three-dimensional comparison of tick-borne flavivirus infection in mammalian and tick cell lines. PLoS One. 2012; 7(10):e47912. doi: 10.1371/journal.pone.0047912. Epub 2012 Oct 24. PubMed PMID: 23112871; PubMed Central PMCID: PMC3480448. 48. Omsland A, Sager J, Nair V, Sturdevant DE, Hackstadt T. Developmental stage- specific metabolic and transcriptional activity of Chlamydia trachomatis in an axenic medium. Proc Natl Acad Sci U S A. 2012 Nov 27; 109(48):19781-5. doi: 10.1073/pnas.1212831109. Epub 2012 Nov 5. PubMed PMID: 23129646; PubMed Central PMCID: PMC3511728. 49. Orrù CD, Hughson AG, Race B, Raymond GJ, Caughey B. Time course of prion seeding activity in cerebrospinal fluid of scrapie-infected hamsters after intratongue and intracerebral inoculations. J Clin Microbiol. 2012 Apr; 50(4):1464-6. doi: 10.1128/JCM.06099-11. Epub 2012 Jan 11. PubMed PMID: 22238438; PubMed

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Central PMCID: PMC3318555. 50. Orrù CD, Wilham JM, Vascellari S, Hughson AG, Caughey B. New generation QuIC assays for prion seeding activity. Prion. 2012 Apr-Jun; 6(2):147-52. doi: 10.4161/pri.19430. Epub 2012 Apr 1. Review. PubMed PMID: 22421206. 51. Peden AH, McGuire LI, Appleford NE, Mallinson G, Wilham JM, Orrú CD, Caughey B, Ironside JW, Knight RS, Will RG, Green AJ, Head MW. Sensitive and specific detection of sporadic Creutzfeldt-Jakob disease brain prion protein using real-time quaking-induced conversion. J Gen Virol. 2012 Feb; 93(Pt 2):438-49. doi: 10.1099/vir.0.033365-0. Epub 2011 Oct 26. PubMed PMID: 22031526; PubMed Central PMCID: PMC3352348. 52. Prescott J, de Wit E, Feldmann H, Munster VJ. The immune response to Nipah virus infection. Arch Virol. 2012 Sep; 157(9):1635-41. doi: 10.1007/s00705-012-1352-5. Epub 2012 Jun 6. Review. PubMed PMID: 22669317; PubMed Central PMCID: PMC3432143. 53. Qiu X, Fernando L, Melito PL, Audet J, Feldmann H, Kobinger G, Alimonti JB, Jones SM. Ebola GP-specific monoclonal antibodies protect mice and guinea pigs from lethal Ebola virus infection. PLoS Negl Trop Dis. 2012; 6(3):e1575. doi: 10.1371/journal.pntd.0001575. Epub 2012 Mar 20. PubMed PMID: 22448295; PubMed Central PMCID: PMC3308939. 54. Rangel A, Race B, Striebel J, Chesebro B. Non-amyloid and amyloid prion protein deposits in prion-infected mice differ in blockage of interstitial brain fluid. Neuropathol Appl Neurobiol. 2012 Sep 24. doi: 10.1111/j.1365-2990.2012.01303.x. [Epub ahead of print] PubMed PMID: 22998478. 55. Rasmussen DL, Kobayashi SD, DeLeo FR. Flexicate molecules as a potential new class of antibiotics. Future Microbiol. 2012 Apr; 7(4):445-8. doi: 10.2217/fmb.12.26. PubMed PMID: 22439721. 56. Raymond GJ, Race B, Hollister JR, Offerdahl DK, Moore RA, Kodali R, Raymond LD, Hughson AG, Rosenke R, Long D, Dorward DW, Baron GS. Isolation of novel synthetic prion strains by amplification in transgenic mice coexpressing wild-type and anchorless prion proteins. J Virol. 2012 Nov; 86(21):11763-78. doi: 10.1128/JVI.01353-12. Epub 2012 Aug 22. PubMed PMID: 22915801; PubMed Central PMCID: PMC3486332. 57. Revelli DA, Boylan JA, Gherardini FC. A non-invasive intratracheal inoculation method for the study of pulmonary melioidosis. Front Cell Infect Microbiol. 2012; 2:164. doi: 10.3389/fcimb.2012.00164. Epub 2012 Dec 20. PubMed PMID: 23267442; PubMed Central PMCID: PMC3526731. 58. Richt JA, Rockx B, Ma W, Feldmann F, Safronetz D, Marzi A, Kobasa D, Strong JE, Kercher L, Long D, Gardner D, Brining D, Feldmann H. Recently emerged swine influenza A virus (H2N3) causes severe pneumonia in Cynomolgus macaques. PLoS One. 2012; 7(7):e39990. doi: 10.1371/journal.pone.0039990. Epub 2012 Jul 11. PubMed PMID: 22808082; PubMed Central PMCID: PMC3394781.

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59. Rigby KM, DeLeo FR. Neutrophils in innate host defense against Staphylococcus aureus infections. Semin Immunopathol. 2012 Mar; 34(2):237-59. doi: 10.1007/s00281- 011-0295-3. Epub 2011 Nov 12. Review. PubMed PMID: 22080185; PubMed Central PMCID: PMC3271231. 60. Rockx-Brouwer D, Chong A, Wehrly TD, Child R, Crane DD, Celli J, Bosio CM. Low dose vaccination with attenuated Francisella tularensis strain SchuS4 mutants protects against tularemia independent of the route of vaccination. PLoS One. 2012; 7(5):e37752. doi: 10.1371/journal.pone.0037752. Epub 2012 May 25. PubMed PMID: 22662210; PubMed Central PMCID: PMC3360632. 61. Safronetz D, Ebihara H, Feldmann H, Hooper JW. The Syrian hamster model of hantavirus pulmonary syndrome. Antiviral Res. 2012 Sep; 95(3):282-92. doi: 10.1016/j.antiviral.2012.06.002. Epub 2012 Jun 15. Review. PubMed PMID: 22705798; PubMed Central PMCID: PMC3425723. 62. Saphire EO, Feldmann H. The variety of study in the field of emerging viruses. Curr Opin Virol. 2012 Apr; 2(2):157-9. doi: 10.1016/j.coviro.2012.03.002. Epub 2012 Mar 23. PubMed PMID: 22482713. 63. Shimojima M, Ströher U, Ebihara H, Feldmann H, Kawaoka Y. Identification of cell surface molecules involved in dystroglycan-independent Lassa virus cell entry. J Virol. 2012 Feb; 86(4):2067-78. doi: 10.1128/JVI.06451-11. Epub 2011 Dec 7. PubMed PMID: 22156524; PubMed Central PMCID: PMC3302412. 64. Schwartz JT, Bandyopadhyay S, Kobayashi SD, McCracken J, Whitney AR, Deleo FR, Allen LA. Francisella tularensis Alters Human Neutrophil Gene Expression: Insights into the Molecular Basis of Delayed Neutrophil Apoptosis. J Innate Immun. 2012 Sep 14. [Epub ahead of print] PubMed PMID: 22986450. 65. Seo KS, Kim JW, Park JY, Viall AK, Minnich SS, Rohde HN, Schnider DR, Lim SY, Hong JB, Hinnebusch BJ, O'Loughlin JL, Deobald CF, Bohach GA, Hovde CJ, Minnich SA. Role of a new intimin/invasin-like protein in Yersinia pestis virulence. Infect Immun. 2012 Oct; 80(10):3559-69. doi: 10.1128/IAI.00294-12. Epub 2012 Jul 30. PubMed PMID: 22851752; PubMed Central PMCID: PMC3457552. 66. Sharma-Kuinkel BK, Ahn SH, Rude TH, Zhang Y, Tong SY, Ruffin F, Genter FC, Braughton KR, Deleo FR, Barriere SL, Fowler VG Jr. Presence of genes encoding panton-valentine leukocidin is not the primary determinant of outcome in patients with hospital-acquired pneumonia due to Staphylococcus aureus. J Clin Microbiol. 2012 Mar; 50(3):848-56. doi: 10.1128/JCM.06219-11. Epub 2012 Jan 11. PubMed PMID: 22205797; PubMed Central PMCID: PMC3295120. 67. Spinner JL, Hinnebusch BJ. The life stage of Yersinia pestis in the flea vector confers increased resistance to phagocytosis and killing by murine polymorphonuclear leukocytes. Adv Exp Med Biol. 2012; 954:159-63. doi: 10.1007/978-1-4614-3561- 7_20. PubMed PMID: 22782759. 68. Spinner JL, Jarrett CO, Larock DL, Miller SI, Collins CM, Hinnebusch BJ. Yersinia pestis insecticidal-like toxin complex (Tc) family proteins: characterization of

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5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: NIH RML scientists broadly study pathogens that cause viral hemorrhagic fevers, viral encephalitis, and certain respiratory diseases. This work employs investigations in cell culture; animal models, including nonhuman primates; reservoir species; and arthropod hosts in order to elucidate the viral pathogenesis, immune responses, molecular evolution, cellular and molecular biology, and vector-host interactions. Specifically, studies include pathogenesis and pathophysiology of high-containment pathogens using molecular technologies; immune responses to infection and vaccination with viral pathogens; vector/reservoir transmission of viral pathogens and development of new vaccine candidates; in vitro and in vivo systems to study the interactions between viral pathogens or viral components and host cells; and epidemiology and ecology of pathogens.

Research activities address pathogenesis studies, vaccinology, and development of therapeutic countermeasures and rapid diagnostic assays in support of the civilian biodefense program.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A, B and C Priority Pathogens

• Overlap Select Agents Including NIAID Category A, B and C Priority Pathogens

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• USDA Select Agents and Toxins • Other pathogens or toxins Including non-Select Agent, NIAID Category A, B and C Priority Pathogens

(iii) Outdoor Studies: None

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Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

National Institutes of Health (NIH), C.W. Bill Young Center for Biodefense and Emerging Infectious Diseases

2. Where is it located (provide both address and geographical location)?

National Institutes of Health, U.S. Department of Health and Human Services 9000 Rockville Pike

Bethesda, Maryland 20892

3. Floor area of laboratory areas by containment level:

BL2 2493 (sqM) BL3 1091 (sqM) BL4 0 (sqM) Total laboratory floor area 3584 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 120

(ii) Division of personnel:

Military 0

Civilian 120

(iii) Division of personnel by category:

Scientists 91

Engineers 0

Technicians 24

Administrative and support staff 5

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Bacteriology, Biology, Chemistry, Immunology, Medicine, Microbiology, Molecular

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Biology, Parasitology, Pathogenesis, Toxinology, Vaccine Evaluation, Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 8

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Health and Human Services (HHS)

(vii) What are the funding levels for the following program areas:

Research $ 36,151,028 Development $ 0 Test and evaluation $ 0 Total $ 36,151,028

(viii) Briefly describe the publication policy of the facility:

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

1. Abdalla H, Srinivasan L, Shah S, Mayer-Barber KD, Sher A, Sutterwala FS, Briken V. Mycobacterium tuberculosis infection of dendritic cells leads to partially caspase-1/11- independent IL-1Î² and IL-18 secretion but not to pyroptosis. PLoS One. 2012; 7(7):e40722. doi: 10.1371/journal.pone.0040722. Epub 2012 Jul 24. PubMed PMID: 22911706; PubMed Central PMCID: PMC3404059. 2. Abrahams GL, Kumar A, Savvi S, Hung AW, Wen S, Abell C, Barry CE 3rd, Sherman DR, Boshoff HI, Mizrahi V. Pathway-selective sensitization of Mycobacterium

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tuberculosis for target-based whole-cell screening. Chem Biol. 2012 Jul 27; 19(7):844- 54. doi: 10.1016/j.chembiol.2012.05.020. PubMed PMID: 22840772; PubMed Central PMCID: PMC3421836. 3. Altmann SE, Brandt CR, Jahrling PB, Blaney JE. Antiviral activity of the EB peptide against zoonotic poxviruses. Virol J. 2012 Jan 6; 9:6. doi: 10.1186/1743-422X-9-6. PubMed PMID: 22225618; PubMed Central PMCID: PMC3275487. 4. Arnold MF, Haag AF, Capewell S, Boshoff HI, James EK, McDonald R, Mair I, Mitchell AM, Kerscher B, Mitchell TJ, Mergaert P, Barry CE 3rd, Scocchi M, Zanda M, Campopiano DJ, Ferguson GP. Partial Complementation of Sinorhizobium meliloti bacA Mutant Phenotypes by the Mycobacterium tuberculosis BacA Protein. J Bacteriol. 2013 Jan; 195(2):389-98. doi: 10.1128/JB.01445-12. Epub 2012 Nov 16. PubMed PMID: 23161027; PubMed Central PMCID: PMC3553841. 5. Arora G, Sajid A, Arulanandh MD, Singhal A, Mattoo AR, Pomerantsev AP, Leppla SH, Maiti S, Singh Y. Unveiling the novel dual specificity protein kinases in Bacillus anthracis: identification of the first prokaryotic dual specificity tyrosine phosphorylation-regulated kinase (DYRK)-like kinase. J Biol Chem. 2012 Aug 3; 287(32):26749-63. doi: 10.1074/jbc.M112.351304. Epub 2012 Jun 18. PubMed PMID: 22711536; PubMed Central PMCID: PMC3411013. 6. Austin SK, Dowd KA, Shrestha B, Nelson CA, Edeling MA, Johnson S, Pierson TC, Diamond MS, Fremont DH. Structural basis of differential neutralization of DENV-1 genotypes by an antibody that recognizes a cryptic epitope. PLoS Pathog. 2012 Oct; 8(10):e1002930. doi: 10.1371/journal.ppat.1002930. Epub 2012 Oct 4. PubMed PMID: 23055922; PubMed Central PMCID: PMC3464233. 7. Bachran C, Abdelazim S, Fattah RJ, Liu S, Leppla SH. Recombinant expression and purification of a tumor-targeted toxin in Bacillus anthracis. Biochem Biophys Res Commun. 2013 Jan 4; 430(1):150-5. doi: 10.1016/j.bbrc.2012.11.055. Epub 2012 Nov 27. PubMed PMID: 23200832; PubMed Central PMCID: PMC3545075. 8. Backes S, Shapiro JS, Sabin LR, Pham AM, Reyes I, Moss B, Cherry S, tenOever BR. Degradation of host microRNAs by poxvirus poly(A) polymerase reveals terminal RNA methylation as a protective antiviral mechanism. Cell Host Microbe. 2012 Aug 16; 12(2):200-10. doi: 10.1016/j.chom.2012.05.019. PubMed PMID: 22901540. 9. Barber DL, Andrade BB, Sereti I, Sher A. Immune reconstitution inflammatory syndrome: the trouble with immunity when you had none. Nat Rev Microbiol. 2012 Jan 9; 10(2):150-6. doi: 10.1038/nrmicro2712. PubMed PMID: 22230950. 10. Bellanti JA, Lin FY, Chu C, Shiloach J, Leppla SH, Benavides GA, Karpas A, Moayeri M, Guo C, Robbins JB, Schneerson R. Phase 1 study of a recombinant mutant protective antigen of Bacillus anthracis. Clin Vaccine Immunol. 2012 Feb;19(2):140-5. doi: 10.1128/CVI.05556-11. Epub 2011 Dec 21. PubMed PMID: 22190398; PubMed Central PMCID: PMC3272932. 11. Bengali Z, Satheshkumar PS, Moss B. Orthopoxvirus species and strain differences in cell entry. Virology. 2012 Nov 25; 433(2):506-12. doi: 10.1016/j.virol.2012.08.044.

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Epub 2012 Sep 20. PubMed PMID: 22999097; PubMed Central PMCID: PMC3470877. 12. Bezrukov SM, Liu X, Karginov VA, Wein AN, Leppla SH, Popoff MR, Barth H, Nestorovich EM. Interactions of high-affinity cationic blockers with the translocation pores of B. anthracis, C. botulinum, and C. perfringens binary toxins. Biophys J. 2012 Sep 19; 103(6):1208-17. doi: 10.1016/j.bpj.2012.07.050. PubMed PMID: 22995493; PubMed Central PMCID: PMC3446695. 13. Boonnak K, Paskel M, Matsuoka Y, Vogel L, Subbarao K. Evaluation of replication, immunogenicity and protective efficacy of a live attenuated cold-adapted pandemic H1N1 influenza virus vaccine in non-human primates. Vaccine. 2012 Aug 17; 30(38):5603-10. doi: 10.1016/j.vaccine.2012.06.088. Epub 2012 Jul 10. PubMed PMID: 22789506; PubMed Central PMCID: PMC3412900. 14. Boonnak K, Subbarao K. Memory CD4+ T cells: beyond "helper" functions. J Clin Invest. 2012 Aug 1; 122(8):2768-70. doi: 10.1172/JCI65208. Epub 2012 Jul 23. PubMed PMID: 22820285; PubMed Central PMCID: PMC3408759. 15. Boshoff HI, Choi I, Nayyar A, Lee YS, Cherian J, Niyomrattanakit P, Dick T, Manjunatha UH, Barry CE 3rd, Spraggon G, Geierstanger BH. Structure of Ddn, the deazaflavin-dependent nitroreductase from Mycobacterium tuberculosis involved in bioreductive activation of PA-824. Structure. 2012 Jan 11; 20(1):101-12. doi: 10.1016/j.str.2011.11.001. PubMed PMID: 22244759; PubMed Central PMCID: PMC3267046. 16. Cann JA, Jahrling PB, Hensley LE, Wahl-Jensen V. Comparative pathology of smallpox and monkeypox in man and macaques. J Comp Pathol. 2013 Jan; 148(1):6-21. doi: 10.1016/j.jcpa.2012.06.007. Epub 2012 Aug 11. PubMed PMID: 22884034; PubMed Central PMCID: PMC3498598. 17. Carroll MW, Choi H, Min S, Hwang S, Park H, Song T, Park Y, Jeon HS, Goldfeder LC, Via LE, Lebron J, Jin B, Cai Y, Barry CE 3rd, Lee M. Rhabdomyolysis in a patient treated with linezolid for extensively drug-resistant tuberculosis. Clin Infect Dis. 2012 Jun; 54(11):1624-7. doi: 10.1093/cid/cis293. Epub 2012 Mar 15. PubMed PMID: 22423128; PubMed Central PMCID: PMC3404720. 18. Carroll MW, Lee M, Cai Y, Hallahan CW, Shaw PA, Min JH, Goldfeder LC, Alekseyev V, Grinkrug S, Kang HS, Hwang S, Park HM, Kang E, Lee SY, Jin B, Park HE, Min S, Park SK, Jeon DS, Via LE, Barry CE 3rd. Frequency of adverse reactions to first- and second-line anti-tuberculosis chemotherapy in a Korean cohort. Int J Tuberc Lung Dis. 2012 Jul; 16(7):961-6. doi: 10.5588/ijtld.11.0574. Epub 2012 May 8. PubMed PMID: 22584241. 19. Cellitti SE, Shaffer J, Jones DH, Mukherjee T, Gurumurthy M, Bursulaya B, Madigan CA, Cheng TY, Layre E, Young DC, McConnell MJ, Debono CA, Murry JP, Wei JR, Barry CE 3rd, Rodriguez GM, Matsunaga I, Rubin EJ, Moody DB. Lipidomic discovery of deoxysiderophores reveals a revised mycobactin biosynthesis pathway in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2012 Jan 24; 109(4):1257-62. doi: 10.1073/pnas.1109958109. Epub 2012 Jan 9. PubMed PMID: 22232695; PubMed

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Central PMCID: PMC3268331. 20. Chakraborty S, Gruber T, Barry CE 3rd, Boshoff HI, Rhee KY. Para-aminosalicylic acid acts as an alternative substrate of folate metabolism in Mycobacterium tuberculosis. Science. 2013 Jan 4; 339(6115):88-91. doi: 10.1126/science.1228980. Epub 2012 Nov 1. PubMed PMID: 23118010. 21. Chakravorty S, Kothari H, Aladegbami B, Cho EJ, Lee JS, Roh SS, Kim H, Kwak H, Lee EG, Hwang SH, Banada PP, Safi H, Via LE, Cho SN, Barry CE 3rd, Alland D. Rapid, high-throughput detection of rifampin resistance and heteroresistance in Mycobacterium tuberculosis by use of sloppy molecular beacon melting temperature coding. J Clin Microbiol. 2012 Jul; 50(7):2194-202. doi: 10.1128/JCM.00143-12. Epub 2012 Apr 25. PubMed PMID: 22535987; PubMed Central PMCID: PMC3405605. 22. Chen Z, Kim L, Subbarao K, Jin H. The 2009 pandemic H1N1 virus induces anti- neuraminidase (NA) antibodies that cross-react with the NA of H5N1 viruses in ferrets. Vaccine. 2012 Mar 28; 30(15):2516-22. doi: 10.1016/j.vaccine.2012.01.090. Epub 2012 Feb 11. PubMed PMID: 22330124. 23. Clark DV, Jahrling PB, Lawler JV. Clinical management of filovirus-infected patients. Viruses. 2012 Sep; 4(9):1668-86. doi: 10.3390/v4091668. Epub 2012 Sep 21. PubMed PMID: 23170178; PubMed Central PMCID: PMC3499825. 24. Cox JH, Ferrari MG, Earl P, Lane JR, Jagodzinski LL, Polonis VR, Kuta EG, Boyer JD, Ratto-Kim S, Eller LA, Pham DT, Hart L, Montefiori D, Ferrari G, Parrish S, Weiner DB, Moss B, Kim JH, Birx D, VanCott TC. Inclusion of a CRF01_AE HIV envelope protein boost with a DNA/MVA prime-boost vaccine: Impact on humoral and cellular immunogenicity and viral load reduction after SHIV-E challenge. Vaccine. 2012 Feb 27; 30(10):1830-40. doi: 10.1016/j.vaccine.2011.12.131. Epub 2012 Jan 9. PubMed PMID: 22234262; PubMed Central PMCID: PMC3324265. 25. Dalton T, Cegielski P, Akksilp S, Asencios L, Campos Caoili J, Cho SN, Erokhin VV, Ershova J, Gler MT, Kazennyy BY, Kim HJ, Kliiman K, Kurbatova E, Kvasnovsky C, Leimane V, van der Walt M, Via LE, Volchenkov GV, Yagui MA, Kang H; Global PETTS Investigators, Akksilp R, Sitti W, Wattanaamornkiet W, Andreevskaya SN, Chernousova LN, Demikhova OV, Larionova EE, Smirnova TG, Vasilieva IA, Vorobyeva AV, Barry CE 3rd, Cai Y, Shamputa IC, Bayona J, Contreras C, Bonilla C, Jave O, Brand J, Lancaster J, Odendaal R, Chen MP, Diem L, Metchock B, Tan K, Taylor A, Wolfgang M, Cho E, Eum SY, Kwak HK, Lee J, Lee J, Min S, Degtyareva I, Nemtsova ES, Khorosheva T, Kyryanova EV, Egos G, Perez MT, Tupasi T, Hwang SH, Kim CK, Kim SY, Lee HJ, Kuksa L, Norvaisha I, Skenders G, Sture I, Kummik T, Kuznetsova T, Somova T, Levina K, Pariona G, Yale G, Suarez C, Valencia E, Viiklepp P. Prevalence of and risk factors for resistance to second-line drugs in people with multidrug-resistant tuberculosis in eight countries: a prospective cohort study. Lancet. 2012 Oct 20; 380(9851):1406-17. doi: 10.1016/S0140-6736(12)60734-X. Epub 2012 Aug 30. Erratum in: Lancet. 2012 Oct 20; 380(9851):1386. PubMed PMID: 22938757. 26. Duckworth BP, Wilson DJ, Nelson KM, Boshoff HI, Barry CE 3rd, Aldrich CC.

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Development of a selective activity-based probe for adenylating enzymes: profiling MbtA Involved in siderophore biosynthesis from Mycobacterium tuberculosis. ACS Chem Biol. 2012 Oct 19; 7(10):1653-8. doi: 10.1021/cb300112x. Epub 2012 Jul 23. PubMed PMID: 22796950; PubMed Central PMCID: PMC3477287. 27. Earl PL, Americo JL, Moss B. Lethal monkeypox virus infection of CAST/EiJ mice is associated with a deficient gamma interferon response. J Virol. 2012 Sep; 86(17):9105- 12. doi: 10.1128/JVI.00162-12. Epub 2012 Jun 13. PubMed PMID: 22696658; PubMed Central PMCID: PMC3416162. 28. Easterbrook JD, Schwartzman LM, Gao J, Kash JC, Morens DM, Couzens L, Wan H, Eichelberger MC, Taubenberger JK. Protection against a lethal H5N1 influenza challenge by intranasal immunization with virus-like particles containing 2009 pandemic H1N1 neuraminidase in mice. Virology. 2012 Oct 10; 432(1):39-44. doi: 10.1016/j.virol.2012.06.003. Epub 2012 Jun 22. PubMed PMID: 22727831. 29. England K, Boshoff HI, Arora K, Weiner D, Dayao E, Schimel D, Via LE, Barry CE 3rd. Meropenem-clavulanic acid shows activity against Mycobacterium tuberculosis in vivo. Antimicrob Agents Chemother. 2012 Jun; 56(6):3384-7. doi: 10.1128/AAC.05690-11. Epub 2012 Mar 26. PubMed PMID: 22450968; PubMed Central PMCID: PMC3370771. 30. Fouchier R, Osterhaus AB, Steinbruner J, Yuen KY, Henderson DA, Klotz L, Sylvester E, Taubenberger JK, Ebright RH, Heymann DL. Preventing pandemics: The fight over flu. Nature. 2012 Jan 15; 481(7381):257-9. doi: 10.1038/481257a. PubMed PMID: 22246325. 31. Fouchier RA, García-Sastre A, Kawaoka Y, Barclay WS, Bouvier NM, Brown IH, Capua I, Chen H, Compans RW, Couch RB, Cox NJ, Doherty PC, Donis RO, Feldmann H, Guan Y, Katz J, Klenk HD, Kobinger G, Liu J, Liu X, Lowen A, Mettenleiter TC, Osterhaus AD, Palese P, Peiris JS, Perez DR, Richt JA, Schultz-Cherry S, Steel J, Subbarao K, Swayne DE, Takimoto T, Tashiro M, Taubenberger JK, Thomas PG, Tripp RA, Tumpey TM, Webby RJ, Webster RG. Pause on Avian Flu Transmission Research. Science. 2012 Jan 20. [Epub ahead of print] PubMed PMID: 22267586. 32. Fouchier RA, García-Sastre A, Kawaoka Y, Barclay WS, Bouvier NM, Brown IH, Capua I, Chen H, Compans RW, Couch RB, Cox NJ, Doherty PC, Donis RO, Feldmann H, Guan Y, Katz J, Klenk HD, Kobinger G, Liu J, Liu X, Lowen A, Mettenleiter TC, Osterhaus AD, Palese P, Peiris JS, Perez DR, Richt JA, Schultz-Cherry S, Steel J, Subbarao K, Swayne DE, Takimoto T, Tashiro M, Taubenberger JK, Thomas PG, Tripp RA, Tumpey TM, Webby RJ, Webster RG. Pause on avian flu transmission research. Science. 2012 Jan 27; 335(6067):400-1. doi: 10.1126/science.335.6067.400. PubMed PMID: 22282787. 33. Goldszmid RS, Caspar P, Rivollier A, White S, Dzutsev A, Hieny S, Kelsall B, Trinchieri G, Sher A. NK cell-derived interferon-Î³ orchestrates cellular dynamics and the differentiation of monocytes into dendritic cells at the site of infection. Immunity. 2012 Jun 29; 36(6):1047-59. doi: 10.1016/j.immuni.2012.03.026. PubMed PMID: 22749354; PubMed Central PMCID: PMC3412151.

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34. Gurumurthy M, Rao M, Mukherjee T, Rao SP, Boshoff HI, Dick T, Barry CE 3rd, Manjunatha UH. A novel F(420) -dependent anti-oxidant mechanism protects Mycobacterium tuberculosis against oxidative stress and bactericidal agents. Mol Microbiol. 2012 Dec 14. doi: 10.1111/mmi.12127. [Epub ahead of print] PubMed PMID: 23240649. 35. Hallengärd D, Applequist SE, Nyström S, Maltais AK, Marovich M, Moss B, Earl P, Nihlmark K, Wahren B, Bråve A. Immunization with multiple vaccine modalities induce strong HIV-specific cellular and humoral immune responses. Viral Immunol. 2012 Oct; 25(5):423-32. doi: 10.1089/vim.2012.0046. PubMed PMID: 23035853. 36. He XS, Sasaki S, Baer J, Khurana S, Golding H, Treanor JJ, Topham DJ, Sangster MY, Jin H, Dekker CL, Subbarao K, Greenberg HB. Heterovariant Cross-Reactive B-Cell Responses Induced by the 2009 Pandemic Influenza Virus A Subtype H1N1 Vaccine. J Infect Dis. 2013 Jan; 207(2):288-96. doi: 10.1093/infdis/jis664. Epub 2012 Oct 29. PubMed PMID: 23107783; PubMed Central PMCID: PMC3532823. 37. Heiss BL, Maximova OA, Thach DC, Speicher JM, Pletnev AG. MicroRNA targeting of neurotropic flavivirus: effective control of virus escape and reversion to neurovirulent phenotype. J Virol. 2012 May; 86(10):5647-59. doi: 10.1128/JVI.07125- 11. Epub 2012 Mar 14. PubMed PMID: 22419812; PubMed Central PMCID: PMC3347253. 38. Hellmich KA, Levinsohn JL, Fattah R, Newman ZL, Maier N, Sastalla I, Liu S, Leppla SH, Moayeri M. Anthrax lethal factor cleaves mouse nlrp1b in both toxin-sensitive and toxin-resistant macrophages. PLoS One. 2012; 7(11):e49741. doi: 10.1371/journal.pone.0049741. Epub 2012 Nov 12. PubMed PMID: 23152930; PubMed Central PMCID: PMC3495862. 39. Howard AR, Moss B. Formation of orthopoxvirus cytoplasmic A-type inclusion bodies and embedding of virions are dynamic processes requiring microtubules. J Virol. 2012 May; 86(10):5905-14. doi: 10.1128/JVI.06997-11. Epub 2012 Mar 21. PubMed PMID: 22438543; PubMed Central PMCID: PMC3347259. 40. Ilyushina NA, Ikizler MR, Kawaoka Y, Rudenko LG, Treanor JJ, Subbarao K, Wright PF. Comparative study of influenza virus replication in MDCK cells and in primary cells derived from adenoids and airway epithelium. J Virol. 2012 Nov; 86(21):11725- 34. doi: 10.1128/JVI.01477-12. Epub 2012 Aug 22. PubMed PMID: 22915797; PubMed Central PMCID: PMC3486302. 41. Jaume M, Yip MS, Kam YW, Cheung CY, Kien F, Roberts A, Li PH, Dutry I, Escriou N, Daeron M, Bruzzone R, Subbarao K, Peiris JS, Nal B, Altmeyer R. SARS CoV subunit vaccine: antibody-mediated neutralisation and enhancement. Hong Kong Med J. 2012 Feb18; Suppl 2:31-6. PubMed PMID: 22311359. 42. Jiao GS, Kim S, Moayeri M, Crown D, Thai A, Cregar-Hernandez L, McKasson L, Sankaran B, Lehrer A, Wong T, Johns L, Margosiak SA, Leppla SH, Johnson AT. Antidotes to anthrax lethal factor intoxication. Part 3: Evaluation of core structures and further modifications to the C2-side chain. Bioorg Med Chem Lett. 2012 Mar 15; 22(6):2242-6. doi: 10.1016/j.bmcl.2012.01.095. Epub 2012 Feb 1. PubMed PMID:

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22342144; PubMed Central PMCID: PMC3295836. 43. Koblansky AA, Jankovic D, Oh H, Hieny S, Sungnak W, Mathur R, Hayden MS, Akira S, Sher A, Ghosh S. Recognition of Profilin by Toll-like Receptor 12 Is Critical for Host Resistance to Toxoplasma gondii. Immunity. 2013 Jan 24; 38(1):119-30. doi: 10.1016/j.immuni.2012.09.016. Epub 2012 Dec 13. PubMed PMID: 23246311. 44. Kugelman JR, Lee MS, Rossi CA, McCarthy SE, Radoshitzky SR, Dye JM, Hensley LE, Honko A, Kuhn JH, Jahrling PB, Warren TK, Whitehouse CA, Bavari S, Palacios G. Ebola virus genome plasticity as a marker of its passaging history: a comparison of in vitro passaging to non-human primate infection. PLoS One. 2012; 7(11):e50316. doi: 10.1371/journal.pone.0050316. Epub 2012 Nov 28. PubMed PMID: 23209706; PubMed Central PMCID: PMC3509072. 45. Kuhn JH, Bao Y, Bavari S, Becker S, Bradfute S, Brister JR, Bukreyev AA, Chandran K, Davey RA, Dolnik O, Dye JM, Enterlein S, Hensley LE, Honko AN, Jahrling PB, Johnson KM, Kobinger G, Leroy EM, Lever MS, Mühlberger E, Netesov SV, Olinger GG, Palacios G, Patterson JL, Paweska JT, Pitt L, Radoshitzky SR, Saphire EO, Smither SJ, Swanepoel R, Towner JS, van der Groen G, Volchkov VE, Wahl-Jensen V, Warren TK, Weidmann M, Nichol ST. Virus nomenclature below the species level: a standardized nomenclature for natural variants of viruses assigned to the family Filoviridae. Arch Virol. 2013 Jan; 158(1):301-11. doi: 10.1007/s00705-012-1454-0. Epub 2012 Sep 23. PubMed PMID: 23001720; PubMed Central PMCID: PMC3535543. 46. Kuhn JH, Radoshitzky SR, Bavari S, Jahrling PB. The International Code of Virus Classification and Nomenclature (ICVCN): proposal to delete Rule 3.41. Arch Virol. 2013 Jan; 158(1):297-9. doi: 10.1007/s00705-012-1453-1. Epub 2012 Aug 31. PubMed PMID: 22932924; PubMed Central PMCID: PMC3541449. 47. Kumar P, Arora K, Lloyd JR, Lee IY, Nair V, Fischer E, Boshoff HI, Barry CE 3rd. Meropenem inhibits D,D-carboxypeptidase activity in Mycobacterium tuberculosis. Mol Microbiol. 2012 Oct; 86(2):367-81. doi: 10.1111/j.1365-2958.2012.08199.x. Epub 2012 Aug 28. PubMed PMID: 22906310; PubMed Central PMCID: PMC3468717. 48. Lakdawala SS, Subbarao K. The ongoing battle against influenza: The challenge of flu transmission. Nat Med. 2012 Oct; 18(10):1468-70. doi: 10.1038/nm.2953. PubMed PMID: 23042349. 49. Lau YF, Wright AR, Subbarao K. The contribution of systemic and pulmonary immune effectors to vaccine-induced protection from H5N1 influenza virus infection. J Virol. 2012 May; 86(9):5089-98. doi: 10.1128/JVI.07205-11. Epub 2012 Feb 29. PubMed PMID: 22379093; PubMed Central PMCID: PMC3347357. 50. Lee IY, Gruber TD, Samuels A, Yun M, Nam B, Kang M, Crowley K, Winterroth B, Boshoff HI, Barry CE 3rd. Structure-activity relationships of antitubercular salicylanilides consistent with disruption of the proton gradient via proton shuttling. Bioorg Med Chem. 2013 Jan 1; 21(1):114-26. doi: 10.1016/j.bmc.2012.10.056. Epub 2012 Nov 15. PubMed PMID: 23211970; PubMed Central PMCID: PMC3525752.

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51. Lee M, Lee J, Carroll MW, Choi H, Min S, Song T, Via LE, Goldfeder LC, Kang E, Jin B, Park H, Kwak H, Kim H, Jeon HS, Jeong I, Joh JS, Chen RY, Olivier KN, Shaw PA, Follmann D, Song SD, Lee JK, Lee D, Kim CT, Dartois V, Park SK, Cho SN, Barry CE 3rd. Linezolid for treatment of chronic extensively drug-resistant tuberculosis. N Engl J Med. 2012 Oct 18; 367(16):1508-18. doi: 10.1056/NEJMoa1201964. PubMed PMID: 23075177. 52. Levinsohn JL, Newman ZL, Hellmich KA, Fattah R, Getz MA, Liu S, Sastalla I, Leppla SH, Moayeri M. Anthrax lethal factor cleavage of Nlrp1 is required for activation of the inflammasome. PLoS Pathog. 2012; 8(3):e1002638. doi: 10.1371/journal.ppat.1002638. Epub 2012 Mar 29. PubMed PMID: 22479187; PubMed Central PMCID: PMC3315489. 53. Lin PL, Dartois V, Johnston PJ, Janssen C, Via L, Goodwin MB, Klein E, Barry CE 3rd, Flynn JL. Metronidazole prevents reactivation of latent Mycobacterium tuberculosis infection in macaques. Proc Natl Acad Sci U S A. 2012 Aug 28; 109(35):14188-93. doi: 10.1073/pnas.1121497109. Epub 2012 Jul 23. PubMed PMID: 22826237; PubMed Central PMCID: PMC3435210. 54. Lin TY, Dowd KA, Manhart CJ, Nelson S, Whitehead SS, Pierson TC. A novel approach for the rapid mutagenesis and directed evolution of the structural genes of west nile virus. J Virol. 2012 Apr; 86(7):3501-12. doi: 10.1128/JVI.06435-11. Epub 2012 Jan 18. PubMed PMID: 22258236; PubMed Central PMCID: PMC3302547. 55. Liu S, Bachran C, Gupta P, Miller-Randolph S, Wang H, Crown D, Zhang Y, Wein AN, Singh R, Fattah R, Leppla SH. Diphthamide modification on eukaryotic elongation factor 2 is needed to assure fidelity of mRNA translation and mouse development. Proc Natl Acad Sci U S A. 2012 Aug 21; 109(34):13817-22. doi: 10.1073/pnas.1206933109. Epub 2012 Aug 6. PubMed PMID: 22869748; PubMed Central PMCID: PMC3427129. 56. Liu S, Zhang Y, Hoover B, Leppla SH. The Receptors that Mediate the Direct Lethality of Anthrax Toxin. Toxins (Basel). 2012 Dec 27; 5(1):1-8. doi: 10.3390/toxins5010001. PubMed PMID: 23271637. 57. Mahnke YD, Greenwald JH, DerSimonian R, Roby G, Antonelli LR, Sher A, Roederer M, Sereti I. Selective expansion of polyfunctional pathogen-specific CD4(+) T cells in HIV-1-infected patients with immune reconstitution inflammatory syndrome. Blood. 2012 Mar 29; 119(13):3105-12. doi: 10.1182/blood-2011-09-380840. Epub 2012 Jan 4. PubMed PMID: 22219223; PubMed Central PMCID: PMC3321870. 58. Mak PA, Rao SP, Ping Tan M, Lin X, Chyba J, Tay J, Ng SH, Tan BH, Cherian J, Duraiswamy J, Bifani P, Lim V, Lee BH, Ling Ma N, Beer D, Thayalan P, Kuhen K, Chatterjee A, Supek F, Glynne R, Zheng J, Boshoff HI, Barry CE 3rd, Dick T, Pethe K, Camacho LR. A high-throughput screen to identify inhibitors of ATP homeostasis in non-replicating Mycobacterium tuberculosis. ACS Chem Biol. 2012 Jul 20; 7(7):1190- 7. doi: 10.1021/cb2004884. Epub 2012 Apr 25. PubMed PMID: 22500615;PubMed Central PMCID: PMC3401038. 59. Memoli MJ, Bristol T, Proudfoot KE, Davis AS, Dunham EJ, Taubenberger JK. In vivo evaluation of pathogenicity and transmissibility of influenza A(H1N1)pdm09

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hemagglutinin receptor binding domain 222 intrahost variants isolated from a single immunocompromised patient. Virology. 2012 Jun 20; 428(1):21-9. doi: 10.1016/j.virol.2012.02.018. PubMed PMID: 22575875; PubMed Central PMCID: PMC3350642. 60. Memoli MJ, Harvey H, Morens DM, Taubenberger JK. Influenza in pregnancy. Influenza Other Respi Viruses. 2012 Nov 21. doi: 10.1111/irv.12055. [Epub ahead of print] PubMed PMID: 23170853. 61. Mendez-Rios JD, Martens CA, Bruno DP, Porcella SF, Zheng ZM, Moss B. Genome sequence of erythromelalgia-related poxvirus identifies it as an ectromelia virus strain. PLoS One. 2012; 7(4):e34604. doi: 10.1371/journal.pone.0034604. Epub 2012 Apr 27. PubMed PMID: 22558090; PubMed Central PMCID: PMC3338725. 62. Moayeri M, Sastalla I, Leppla SH. Anthrax and the inflammasome. Microbes Infect. 2012 May; 14(5):392-400. doi: 10.1016/j.micinf.2011.12.005. Epub 2011 Dec 17. Review. PubMed PMID: 22207185; PubMed Central PMCID: PMC3322314. 63. Morens DM, Subbarao K, Taubenberger JK. Engineering H5N1 avian influenza viruses to study human adaptation. Nature. 2012 Jun 20; 486(7403):335-40. doi: 10.1038/nature11170. PubMed PMID: 22722191. 64. Morens DM, Taubenberger JK. 1918 influenza, a puzzle with missing pieces. Emerg Infect Dis. 2012 Feb; 18(2):332-5. doi: 10.3201/eid1802.111409. PubMed PMID: 22304897; PubMed Central PMCID: PMC3310470. 65. Moss B. Poxvirus cell entry: how many proteins does it take? Viruses. 2012 May; 4(5):688-707. doi: 10.3390/v4050688. Epub 2012 Apr 27. Review. PubMed PMID: 22754644; PubMed Central PMCID: PMC3386626. 66. O'Donnell CD, Vogel L, Wright A, Das SR, Wrammert J, Li GM, McCausland M, Zheng NY, Yewdell JW, Ahmed R, Wilson PC, Subbarao K. Antibody pressure by a human monoclonal antibody targeting the 2009 pandemic H1N1 virus hemagglutinin drives the emergence of a virus with increased virulence in mice. MBio. 2012 May 29; 3(3). doi:pii: e00120-12. 10.1128/mBio.00120-12. Print 2012. PubMed PMID: 22647789; PubMed Central PMCID: PMC3372962. 67. O'Donnell CD, Wright A, Vogel LN, Wei CJ, Nabel GJ, Subbarao K. Effect of priming with H1N1 influenza viruses of variable antigenic distances on challenge with 2009 pandemic H1N1 virus. J Virol. 2012 Aug; 86(16):8625-33. doi: 10.1128/JVI.00147-12. Epub 2012 Jun 6. PubMed PMID: 22674976; PubMed Central PMCID: PMC3421718. 68. Papaneri AB, Wirblich C, Cann JA, Cooper K, Jahrling PB, Schnell MJ, Blaney JE. A replication-deficient rabies virus vaccine expressing Ebola virus glycoprotein is highly attenuated for neurovirulence. Virology. 2012 Dec 5; 434(1):18-26. doi: 10.1016/j.virol.2012.07.020. Epub 2012 Aug 11. PubMed PMID: 22889613; PubMed Central PMCID: PMC3484205. 69. Papaneri AB, Wirblich C, Cooper K, Jahrling PB, Schnell MJ, Blaney JE. Further characterization of the immune response in mice to inactivated and live rabies vaccines expressing Ebola virus glycoprotein. Vaccine. 2012 Sep 21; 30(43):6136-41. doi:

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10.1016/j.vaccine.2012.07.073. Epub 2012 Aug 8. PubMed PMID: 22884661; PubMed Central PMCID: PMC3434297. 70. Pearce EJ, Caspar P, Grzych JM, Lewis FA, Sher A. Pillars article: downregulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni. J. Exp. Med. 1991. 173: 159-166. J Immunol. 2012 Aug 1; 189(3):1104-11. PubMed PMID: 22815380. 71. Peters DE, Zhang Y, Molinolo AA, Miller-Randolph S, Szabo R, Bugge TH, Leppla SH, Liu S. Capillary morphogenesis protein-2 is required for mouse parturition by maintaining uterine collagen homeostasis. Biochem Biophys Res Commun. 2012 Jun 8; 422(3):393-7. doi: 10.1016/j.bbrc.2012.04.160. Epub 2012 May 7. PubMed PMID: 22575514; PubMed Central PMCID: PMC3376708. 72. Pierson TC, Kuhn RJ. Capturing a virus while it catches its breath. Structure. 2012 Feb 8; 20(2):200-2. doi: 10.1016/j.str.2012.01.014. PubMed PMID: 22325768. 73. Pierson TC, Diamond MS. Degrees of maturity: the complex structure and biology of flaviviruses. Curr Opin Virol. 2012 Apr; 2(2):168-75. doi: 10.1016/j.coviro.2012.02.011. Epub 2012 Mar 23. Review. PubMed PMID: 22445964. 74. Pierson TC, Yewdell JW. Measles immunometrics. Proc Natl Acad Sci U S A. 2012 Sep 11; 109(37):14724-5. doi: 10.1073/pnas.1212243109. Epub 2012 Aug 30. PubMed PMID: 22936050; PubMed Central PMCID: PMC3443159. 75. Pilz IH, Di Pasquale G, Rzadzinska A, Leppla SH, Chiorini JA. Mutation in the platelet-derived growth factor receptor alpha inhibits adeno-associated virus type 5 transduction. Virology. 2012 Jun 20; 428(1):58-63. doi: 10.1016/j.virol.2012.03.004. Epub 2012 Apr 20. PubMed PMID: 22520943; PubMed Central PMCID: PMC3350617. 76. Qi L, Davis AS, Jagger BW, Schwartzman LM, Dunham EJ, Kash JC, Taubenberger JK. Analysis by single-gene reassortment demonstrates that the 1918 influenza virus is functionally compatible with a low-pathogenicity avian influenza virus in mice. J Virol. 2012 Sep; 86(17):9211-20. doi: 10.1128/JVI.00887-12. Epub 2012 Jun 20. PubMed PMID: 22718825; PubMed Central PMCID: PMC3416129. 77. Radoshitzky SR, Kuhn JH, de Kok-Mercado F, Jahrling PB, Bavari S. Drug discovery technologies and strategies for Machupo virus and other New World arenaviruses. Expert Opin Drug Discov. 2012 Jul; 7(7):613-32. doi: 10.1517/17460441.2012.687719. Epub 2012 May 19. Review. PubMed PMID: 22607481; PubMed Central PMCID: PMC3426302. 78. Ratto-Kim S, Currier JR, Cox JH, Excler JL, Valencia-Micolta A, Thelian D, Lo V, Sayeed E, Polonis VR, Earl PL, Moss B, Robb ML, Michael NL, Kim JH, Marovich MA. Heterologous prime-boost regimens using rAd35 and rMVA vectors elicit stronger cellular immune responses to HIV proteins than homologous regimens. PLoS One. 2012; 7(9):e45840. doi: 10.1371/journal.pone.0045840. Epub 2012 Sep 26. PubMed PMID: 23049876; PubMed Central PMCID: PMC3458867. 79. Rothfuchs AG, Roffê E, Gibson A, Cheever AW, Ezekowitz RA, Takahashi K, Steindel

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M, Sher A, Báfica A. Mannose-binding lectin regulates host resistance and pathology during experimental infection with Trypanosoma cruzi. PLoS One. 2012; 7(11):e47835. doi: 10.1371/journal.pone.0047835. Epub 2012 Nov 6. PubMed PMID: 23139754; PubMed Central PMCID: PMC3490958. 80. Sacksteder KA, Protopopova M, Barry CE 3rd, Andries K, Nacy CA. Discovery and development of SQ109: a new antitubercular drug with a novel mechanism of action. Future Microbiol. 2012 Jul; 7(7):823-37. doi: 10.2217/fmb.12.56. Review. PubMed PMID: 22827305; PubMed Central PMCID: PMC3480206. 81. Sastalla I, Leppla SH. Occurrence, recognition, and reversion of spontaneous, sporulation-deficient Bacillus anthracis mutants that arise during laboratory culture. Microbes Infect. 2012 May; 14(5):387-91. doi: 10.1016/j.micinf.2011.11.009. Epub 2011 Nov 28. Review. PubMed PMID: 22166343; PubMed Central PMCID: PMC3306515. 82. Sastalla I, Tang S, Crown D, Liu S, Eckhaus MA, Hewlett IK, Leppla SH, Moayeri M. Anthrax edema toxin impairs clearance in mice. Infect Immun. 2012 Feb; 80(2):529-38. doi: 10.1128/IAI.05947-11. Epub 2011 Nov 21. PubMed PMID: 22104108; PubMed Central PMCID: PMC3264307. 83. Shi M, Jagger BW, Wise HM, Digard P, Holmes EC, Taubenberger JK. Evolutionary conservation of the PA-X open reading frame in segment 3 of influenza A virus. J Virol. 2012 Nov; 86(22):12411-3. doi: 10.1128/JVI.01677-12. Epub 2012 Sep 5. PubMed PMID: 22951836; PubMed Central PMCID: PMC3486490. 84. Shi CS, Shenderov K, Huang NN, Kabat J, Abu-Asab M, Fitzgerald KA, Sher A, Kehrl JH. Activation of autophagy by inflammatory signals limits IL-1Î² production by targeting ubiquitinated inflammasomes for destruction. Nat Immunol. 2012 Jan 29; 13(3):255-63. doi: 10.1038/ni.2215. PubMed PMID: 22286270. 85. Shrestha B, Austin SK, Dowd KA, Prasad AN, Youn S, Pierson TC, Fremont DH, Ebel GD, Diamond MS. Complex phenotypes in mosquitoes and mice associated with neutralization escape of a Dengue virus type 1 monoclonal antibody. Virology. 2012 Jun 5; 427(2):127-34. doi: 10.1016/j.virol.2012.02.010. Epub 2012 Mar 9. PubMed PMID: 22406169; PubMed Central PMCID: PMC3312934. 86. Sitaraman R, Leppla SH. Methylation-dependent DNA restriction in Bacillus anthracis. Gene. 2012 Feb 15; 494(1):44-50. doi: 10.1016/j.gene.2011.11.061. Epub 2011 Dec 8. PubMed PMID: 22178763; PubMed Central PMCID: PMC3265652. 87. Sun G, Luo T, Yang C, Dong X, Li J, Zhu Y, Zheng H, Tian W, Wang S, Barry CE 3rd, Mei J, Gao Q. Dynamic population changes in Mycobacterium tuberculosis during acquisition and fixation of drug resistance in patients. J Infect Dis. 2012 Dec 1; 206(11):1724-33. doi: 10.1093/infdis/jis601. Epub 2012 Sep 14. PubMed PMID: 22984115; PubMed Central PMCID: PMC3488197. 88. Tahlan K, Wilson R, Kastrinsky DB, Arora K, Nair V, Fischer E, Barnes SW, Walker JR, Alland D, Barry CE 3rd, Boshoff HI. SQ109 targets MmpL3, a membrane transporter of trehalose monomycolate involved in mycolic acid donation to the cell

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wall core of Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2012 Apr; 56(4):1797-809. doi: 10.1128/AAC.05708-11. Epub 2012 Jan 17. PubMed PMID: 22252828; PubMed Central PMCID: PMC3318387. 89. Talaat KR, Karron RA, Liang PH, McMahon BA, Luke CJ, Thumar B, Chen GL, Min JY, Lamirande EW, Jin H, Coelingh KL, Kemble GW, Subbarao K. An open-label phase I trial of a live attenuated H2N2 influenza virus vaccine in healthy adults. Influenza Other Respi Viruses. 2013 Jan; 7(1):66-73. doi: 10.1111/j.1750- 2659.2012.00350.x. Epub 2012 Mar 14. PubMed PMID: 22417012; PubMed Central PMCID: PMC3527634. 90. Taubenberger JK, Baltimore D, Doherty PC, Markel H, Morens DM, Webster RG, Wilson IA. Reconstruction of the 1918 influenza virus: unexpected rewards from the past. MBio. 2012 Sep 11; 3(5). doi:pii: e00201-12. 10.1128/mBio.00201-12. Print 2012. Review. PubMed PMID: 22967978; PubMed Central PMCID: PMC3448162. 91. Vargas M, Karamsetty R, Leppla SH, Chaudry GJ. Correction: Broad Expression Analysis of Human ANTXR1/TEM8 Transcripts Reveals Differential Expression and Novel Splizce Variants. PLoS One. 2012; 7(10). doi: 10.1371/annotation/cebf633f- 19e7-496b-b370-c0f1b1aea888. Epub 2012 Oct 22. PubMed PMID: 23272019; PubMed Central PMCID: PMC3525693. 92. Vargas M, Karamsetty R, Leppla SH, Chaudry GJ. Broad expression analysis of human ANTXR1/TEM8 transcripts reveals differential expression and novel Splizce variants. PLoS One. 2012; 7(8):e43174. doi: 10.1371/journal.pone.0043174. Epub 2012 Aug 17. PubMed PMID: 22912819; PubMed Central PMCID: PMC3422265. 93. Verma A, White M, Vathipadiekal V, Tripathi S, Mbianda J, Ieong M, Qi L, Taubenberger JK, Takahashi K, Jensenius JC, Thiel S, Hartshorn KL. Human H-ficolin inhibits replication of seasonal and pandemic influenza A viruses. J Immunol. 2012 Sep 1; 189(5):2478-87. doi: 10.4049/jimmunol.1103786. Epub 2012 Jul 30. PubMed PMID: 22851708. 94. Via LE, Schimel D, Weiner DM, Dartois V, Dayao E, Cai Y, Yoon YS, Dreher MR, Kastenmayer RJ, Laymon CM, Carny JE, Flynn JL, Herscovitch P, Barry CE 3rd. Infection dynamics and response to chemotherapy in a rabbit model of tuberculosis using [18F]2-fluoro-deoxy-D-glucose positron emission tomography and computed tomography. Antimicrob Agents Chemother. 2012 Aug; 56(8):4391-402. doi: 10.1128/AAC.00531-12. Epub 2012 Jun 11. PubMed PMID: 22687508; PubMed Central PMCID: PMC3421588. 95. Viboud C, Eisenstein J, Reid AH, Janczewski TA, Morens DM, Taubenberger JK. Age- and sex-specific mortality associated with the 1918-1919 influenza pandemic in Kentucky. J Infect Dis. 2013 Mar; 207(5):721-9. doi: 10.1093/infdis/jis745. Epub 2012 Dec 10. PubMed PMID: 23230061; PubMed Central PMCID: PMC3563305. 96. von Moltke J, Trinidad NJ, Moayeri M, Kintzer AF, Wang SB, van Rooijen N, Brown CR, Krantz BA, Leppla SH, Gronert K, Vance RE. Rapid induction of inflammatory lipid mediators by the inflammasome in vivo. Nature. 2012 Oct 4; 490(7418):107-11. doi: 10.1038/nature11351. Epub 2012 Aug 19. PubMed PMID: 22902502; PubMed

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Central PMCID: PMC3465483. 97. Warren RD, Cotter CA, Moss B. Reverse genetics analysis of poxvirus intermediate transcription factors. J Virol. 2012 Sep; 86(17):9514-9. doi: 10.1128/JVI.06902-11. Epub 2012 Jun 27. PubMed PMID: 22740406; PubMed Central PMCID: PMC3416170. 98. Wasmuth JD, Pszenny V, Haile S, Jansen EM, Gast AT, Sher A, Boyle JP, Boulanger MJ, Parkinson J, Grigg ME. Integrated bioinformatic and targeted deletion analyses of the SRS gene superfamily identify SRS29C as a negative regulator of Toxoplasma virulence. MBio. 2012 Nov 13; 3(6). doi:pii: e00321-12. 10.1128/mBio.00321-12. PubMed PMID: 23149485; PubMed Central PMCID: PMC3509429. 99. Wein AN, Liu S, Zhang Y, McKenzie AT, Leppla SH. Tumor therapy with a urokinase plasminogen activator-activated anthrax lethal toxin alone and in combination with paclitaxel. Invest New Drugs. 2013 Feb; 31(1):206-12. doi: 10.1007/s10637-012-9847- 1. Epub 2012 Jul 28. PubMed PMID: 22843210. 100. Wein AN, Williams BN, Liu S, Ermolinsky B, Provenzano D, Abagyan R, Orry A, Leppla SH, Peredelchuk M. Small molecule inhibitors of Bacillus anthracis protective antigen proteolytic activation and oligomerization. J Med Chem. 2012 Sep 27; 55(18):7998-8006. Epub 2012 Sep 18. PubMed PMID: 22954387; PubMed Central PMCID: PMC3474531. 101. Wise HM, Hutchinson EC, Jagger BW, Stuart AD, Kang ZH, Robb N, Schwartzman LM, Kash JC, Fodor E, Firth AE, Gog JR, Taubenberger JK, Digard P. Identification of a novel splice variant form of the influenza A virus M2 ion channel with an antigenically distinct ectodomain. PLoS Pathog. 2012 Nov; 8(11):e1002998. doi: 10.1371/journal.ppat.1002998. Epub 2012 Nov 1. PubMed PMID: 23133386; PubMed Central PMCID: PMC3486900. 102. Xiao YL, Kash JC, Beres SB, Sheng ZM, Musser JM, Taubenberger JK. High- throughput RNA sequencing of a formalin-fixed, paraffin-embedded autopsy lung tissue sample from the 1918 influenza pandemic. J Pathol. 2012 Nov 26. doi: 10.1002/path.4145. [Epub ahead of print] PubMed PMID: 23180419. 103. Yang Z, Martens CA, Bruno DP, Porcella SF, Moss B. Pervasive initiation and 3'- end formation of poxvirus postreplicative RNAs. J Biol Chem. 2012 Sep 7; 287(37):31050-60. doi: 10.1074/jbc.M112.390054. Epub 2012 Jul 24. PubMed PMID: 22829601; PubMed Central PMCID: PMC3438937.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: At the C.W. Bill Young Center for Biodefense and Emerging Infectious Diseases, the Laboratory of Infectious Diseases (LID) focuses on viral vaccine development, host immune response to viruses, and viral molecular biology and genetics. Newer programs

Page 162 of 237 focus on developing vaccines, from basic research to clinical trials.

The Laboratory of Bacterial Diseases (LBD) focuses on the development of diagnostics, vaccines, and therapeutics for biodefense. Specifc research concerns the identification and analysis of bacterial virulence factors and their genetic regulation; structure-function analysis of bacterial proteins and other factors; and disease pathogenesis.

The Laboratory of Viral Diseases (LVD) studies the basic mechanisms of viral entry into cells, regulation of viral gene expression, viral DNA replication, assembly and transport of viral proteins and particles, viral virulence, and humoral and cellular immunity, for DNA and RNA viruses. Applied research includes development of recombinant expression vectors, candidate vaccines, and antiviral agents.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A and B Priority Pathogens

• Overlap Select Agents Including NIAID Category A Priority Pathogens

• USDA Select Agents and Toxins • Other pathogens or toxins Including non-Select Agent, NIAID Category A, B and C Priority Pathogens

(iii) Outdoor Studies: None

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Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

National Institutes of Health (NIH), Dale and Betty Bumpers Vaccine Research Center

2. Where is it located (provide both address and geographical location)?

National Institutes of Health, US Department of Health and Human Services 9000 Rockville Pike

Bethesda, Maryland 20892

3. Floor area of laboratory areas by containment level:

BL2 89 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 89 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 9

(ii) Division of personnel:

Military 0

Civilian 9

(iii) Division of personnel by category:

Scientists 9

Engineers 0

Technicians 0

Administrative and support staff 0

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Biology, Chemistry, Immunology, Microbiology, Molecular Biology, Pathogenesis, Toxinology, Vaccine Evaluation, Virology

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(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 2

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Health and Human Services (HHS)

(vii) What are the funding levels for the following program areas:

Research $ 774,548 Development $ 0 Test and evaluation $ 0 Total $ 774,548

(viii) Briefly describe the publication policy of the facility:

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

1. Fausther-Bovendo H, Mulangu S, Sullivan NJ. Ebolavirus vaccines for humans and apes. Curr Opin Virol. 2012 Jun; 2(3):324-9. doi: 10.1016/j.coviro.2012.04.003. Epub 2012 May 4. Review. PubMed PMID: 22560007; PubMed Central PMCID: PMC3397659.

2. Misasi J, Chandran K, Yang JY, Considine B, Filone CM, CÃ´té M, Sullivan N, Fabozzi G, Hensley L, Cunningham J. Filoviruses require endosomal cysteine proteases for entry but exhibit distinct protease preferences. J Virol. 2012 Mar; 86(6):3284-92. doi: 10.1128/JVI.06346-11. Epub 2012 Jan 11. PubMed PMID: 22238307; PubMed Central PMCID: PMC3302294.

Page 165 of 237

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: The research focus of the Biodefense Research Laboratory, Vaccine Research Center (VRC) comprises three areas:

1. Development of vaccines and antivirals against hemorrhagic fever viruses such as Ebola, Marburg and Lassa 2. Studies of the mechanism of vaccine-induced immune protection 3. Basic research to understand the mechanism of virus replication (entry) and neutralization

(ii) Agents Microorganisms and/or Toxins:

• Other pathogens or toxins

(iii) Outdoor Studies: None

Page 166 of 237

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Foreign Disease-Weed Science Research Unit

2. Where is it located (provide both address and geographical location)?

1301 Ditto Avenue Fort Detrick, Maryland 21702

3. Floor area of laboratory areas by containment level:

BL2 105 (sqM) BL3 950 (sqM) BL4 0 (sqM) Total laboratory floor area 1055 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 36

(ii) Division of personnel:

Military 0

Civilian 36

(iii) Division of personnel by category:

Scientists 13

Engineers 0

Technicians 16

Administrative and support staff 7

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Agronomy, Biological Control, Horticulture, Plant Biochemistry, Plant Molecular Biology, Plant Pathology, Plant Physiology, Plant Virology, Weed Science

Page 167 of 237

(v) Are contractor staff working in the facility? If so, provide an approximate number.

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Agriculture

(vii) What are the funding levels for the following program areas:

Research $ 5,600,000 Development $ 0 Test and evaluation $ 0 Total $ 5,600,000

(viii) Briefly describe the publication policy of the facility:

All scientific research data is available for publication in peer-reviewed publications after review for dual use determination. All scientists are required to have minimum of two peer- reviewed publications per year. They are encouraged to present research at scientific conferences and publish in books and proceedings.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

1. Berner, D. Cavin, C.A., Erper, I., and Tunali, B. 2012 First report of anthracnose of mile-a-minute (Persicaria perfoliata) caused by Colletotrichum gloeosporioides in Turkey. Plant Disease. 96(10):1578. 2. Bonde, M.R., Nester, S.E., Berner, D.K. 2012. Effects of post-dew period temperature on development of phakopsora pachyrhizi on soybean. Phytopathology. 102:761-768.

3. Bruckart, W.L., Eskandari, F., Berner, D.K., Aime, M.C. 2012. Comparison of Puccinia acroptili from Eurasia and the USA. Botany. 90:465-471. 4. Cruz, C.D., Bockus, W.W., Stack, J.P., Tang, X., Valent, B.S., Pedley, K.F., Peterson, G.L. 2012. Preliminary assessment of resistance among U.S. wheat cultivars to the Triticum pathotype of Magnaporthe oryzae. Plant Disease. 96:1501-1505. 5. Kim, K., Unfried, J.R., Hyten, D.L., Frederick, R.D., Hartman, G.L., Nelson, R.L.,

Page 168 of 237

Song, Q., Diers, B.W. 2012. Molecular mapping of soybean rust resistance in soybean accession PI 561356 and SNP haplotype analysis of the Rpp1 region in diverse germplasm. Theoretical and Applied Genetics. 125:1339-1352. 6. Luster, D.G., Mcmahon, M.B., Edwards, H.H., Boerma, B.L., Miller, S.A., Dorrance, A.E. 2012. Novel phakopsora pachyrhizi extracellular proteins are ideal targets for immunological diagnostic assays. Applied and Environmental Microbiology. 78(11):3890-3895. 7. Stone, C.L., Mcmahon, M.B., Fortis, L.L., Nunez, A., Smythers, G.W., Luster, D.G., Frederick, R.D. 2012. Gene expression and proteomic analysis of the formation of P. pachyrhizi appressoria. Biomed Central (BMC) Genomics. 13:269. 8. Widmer, T.L., Shishkoff, N., Dodge, S.C. 2012. Root susceptibility and inoculum production from roots of Eastern United States oak species to Phytophthora ramorum. Plant Disease. 96:1675-1682.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: The USDA, Agricultural Research Service, Foreign Disease-Weed Science Research Unit has two distinct missions united by a common relationship to plant pathology and the unit's unique BL-3 plant pathogen laboratory and greenhouse containment facilities.

The mission of the foreign disease program is to develop techniques for the rapid detection and identification of new and emerging crop pathogens, and to provide fundamental information on emerging pathogens for risk assessment and the development of practical phytosanitary regulations for the import and export of agricultural commodities and germplasm.

The mission of the weed biological control program is to collect foreign pathogens overseas from weeds in their native habitat, and to evaluate, characterize and release the pathogens in the U.S. for biological control of introduced weeds, leading to improved, sustainable weed control practices in agricultural systems with reduced dependence on chemical herbicides.

(ii) Agents Microorganisms and/or Toxins:

USDA PLANT PROTECTION AND QUARANTINE (PPQ) Select Agents and • Toxins • Other pathogens or toxins

The agents studied are foreign and/or emerging pathogens of plants that have an agricultural base. The agents studied include viruses, bacteria, and fungi. The majority of the agents Page 169 of 237 studied are not classified by USDA as select agents. The agents classified as select agents are pathogens that pose a threat to U.S. plant production systems, agricultural economy, and exports.

(iii) Outdoor Studies: None

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Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

National Animal Disease Center (NADC)

2. Where is it located (provide both address and geographical location)?

1920 Dayton Avenue Ames, Iowa 50010

3. Floor area of laboratory areas by containment level:

BL2 4410 (sqM) BL3 2489 (sqM) BL4 0 (sqM) Total laboratory floor area 6899 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 284

(ii) Division of personnel:

Military 0

Civilian 284

(iii) Division of personnel by category:

Scientists 46

Engineers 0

Technicians 84

Administrative and support staff 154

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Agricultural Engineering, Animal Science, Biochemistry, Bioinformatics, Biology, Biotechnology, Cell Biology, Clinical Immunology, Computational Biology, Ecology, Genetics, Genomics, Immunology, Infectious Disease, Mass Spectrometry, Mass

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Spectrometry Biochemistry, Microbiology, Molecular Biology, Pathogenesis, Pathology, Physiology, Prionology, Proteomics, Statistics, Structural Biology, Vaccine Evaluation, Veterinary Clinical Research, Veterinary Medicine, Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 5

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Agriculture

(vii) What are the funding levels for the following program areas:

Research $ 32,000,000 Development $ 0 Test and evaluation $ 0 Total $ 32,000,000

(viii) Briefly describe the publication policy of the facility:

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

1. Allen, A.J., Stabel, J.R., Robbe-Austerman, S., Park, K.T., Palmer, M.V., Barrington, G.M., Lahmers, K.K., Hamilton, M.J., Davis, W.C. 2012. Depletion of CD4 T lymphocytes at the time of infection with M. avium subsp. paratuberculosis does not accelerate disease progression. Veterinary Immunology and Immunopathology. 149(3- 4):286-291. 2. Bannantine, J.P., Lingle, C.K., Stabel, J.R., Ramyar, K.X., Garcia, B.L., Raeber, A., Schacher, P., Kapur, V., Geisbrecht, B.V. 2012. MAP1272c encodes a NlpC/P60 protein, an antigen detected in cattle with Johne's Disease. Clinical and Vaccine

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Immunology. 19(7):1083-1092. 3. Bannantine, J.P., Wu, C., Hsu, C., Zhou, S., Schwartz, D.C., Bayles, D.O., Paustian, M.L., Alt, D.P., Sreevatsan, S., Kapur, V., Talaat, A.M. 2012. Genome sequencing of ovine isolates of Mycobacterium avium subspecies paratuberculosis offer insights into host association. Biomed Central (BMC) Genomics [serial online]. 13:89. 4. Bauermann, F.V., Flores, E.F., Ridpath, J.F. 2012. Antigenic relationships between bovine viral diarrhea virus 1 and 2 and HoBi virus: Possible impacts on diagnosis and control. Journal of Veterinary Diagnostic Investigation. 24(2):253-261. 5. Bradner, L., Robbe-Austerman, S., Beitz, D., Stabel, J.R. 2012. Optimization of methods for the detection of Mycobacterium avium subsp. paratuberculosis in milk and colostrum of naturally infected dairy cows. In: Proceedings of the 11th International Colloquium on Paratuberculosis, February 5-10, 2012, Sydney, Australia. p. 71-73. 6. Braucher, D.R., Henningson, J.N., Loving, C.L., Vincent, A.L., Kim, E., Steitz, J., Gambotto, A.A., Kehrli, Jr., M.E. 2012. Intranasal vaccination with replication- defective adenovirus type 5 encoding influenza virus hemagglutinin elicits protective immunity to homologous challenge and partial protection to heterologous challenge in pigs. Clinical and Vaccine Immunology. 19(11):1722-1729. 7. Briggs, R.E., Tabatabai, L.B., Tatum, F.M. 2012. Mucosal and parenteral vaccination against pneumonic pasteurellosis in cattle with a modified-live in-frame lktA deletion mutant of Mannheimia haemolytica. Microbial Pathogenesis. 52(5):302-309. 8. Brockmeier, S.L., Loving, C.L., Nelson, E.A., Miller, L.C., Nicholson, T.L., Register, K.B., Grubman, M.J., Brough, D.E., Kehrli, Jr., M.E. 2012. The presence of alpha interferon at the time of infection alters the innate and adaptive immune responses to porcine reproductive and respiratory syndrome virus. Clinical and Vaccine Immunology. 19(4):508-514. 9. Brockmeier, S.L., Loving, C.L., Vorwald, A.C., Kehrli, Jr., M.E., Baker, R.B., Nicholson, T.L., Lager, K.M., Miller, L.C., Faaberg, K.S. 2012. Genomic sequence and virulence comparison of four Type 2 porcine reproductive and respiratory syndrome virus strains. Virus Research. 169(1):212-221. 10. Brockmeier, S.L., Register, K.B., Nicholson, T.L., Loving, C.L. 2012. Bordetellosis. In: Zimmerman, J., Karriker, L., Ramirez, A., Schwartz, K., Stevenson, G., editors. Diseases of Swine. 10th edition. Ames, IA: Iowa State University Press. pp. 670-679. 11. Brunelle, B.W., Sensabaugh, G.F. 2012. Nucleotide and phylogenetic analyses of the Chlamydia trachomatis ompA gene indicates it is a hotspot for mutation. BMC Research Notes [serial online]. 5(53). 12. Bunge, J., Bohning, D., Allen, H.K., Foster, J. 2012. Estimating population diversity with unreliable low frequency counts. Pacific Symposium on Biocomputing (PSB) [serial online]. 17:203-212. 13. Bunge, J., Woodard, L., Bohning, D., Foster, J.A., Connolly, S., Allen, H.K. 2012. Estimating population diversity with CatchAll. Bioinformatics. 28(7):1045-1047.

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14. Casas, E., Thallman, R.M., Cundiff, L.V. 2012. Birth and weaning traits in crossbred cattle from Hereford, Angus, Norwegian Red, Swedish Red and White, Wagyu, and Friesian sires. Journal of Animal Science. 90:2916-2920. 15. Casey, T., Connell, T.D., Holmes, R.K., Whipp, S.C. 2012. Evaluation of heat-labile enterotoxins type IIa and type IIb in the pathogenicity of enterotoxigenic Escherichia coli for neonatal pigs. Veterinary Microbiology. 3(18). 16. Chen, J., Faisal, S.M., Chandra, S., Mcdonough, S.P., Moreira, M.A., Scaria, J., Chang, C., Bannantine, J.P., Akey, B., Chang, Y. 2012. Immunogenicity and protective efficacy of the Mycobacterium avium subsp. paratuberculosis attenuated mutants against challenge in a mouse model. Vaccine. 30(19):3015-3025. 17. Cheung, A.K. 2012. Porcine circovirus: transcription and DNA replication. Virus Research. 164(1-2):46-53. 18. Cheung, A.K. 2012. Replicative intermediates of porcine circovirus in animal tissue cultured cells or in bacteria undergoing copy-release replication. Virology. 434(1):38- 42. 19. Ciacci Zanella, J.R., Vincent, A.L., Zanella, E.L., Lorusso, A., Loving, C.L., Brockmeier, S.L., Gauger, P.C., Janke, B.H., Gramer, M.R. 2012. Comparison of human-like H1 (delta-cluster) influenza A viruses in the swine host. Influenza Research and Treatment. 20. Donahue, M., Godden, S., Bey, R., Wells, S., Oakes, J., Sreevatsan, S., Stabel, J.R., Fetrow, J. 2012. Heat treatment of colostrum on commercial dairy farms decreases colostrum microbial counts while maintaining colostrum immunoglobulin G concentrations. Journal of Dairy Science. 95(5):2697-2702. 21. Eshghi, A., Pinne, M., Haake, D.A., Zuerner, R.L., Frank, A.T., Cameron, C.E. 2012. Methylation and in vivo expression of the surface-exposed Leptospira interrogans outer-membrane protein OmpL32. Microbiology. 158(Pt. 3):622-635. 22. Gauger, P.C., Faaberg, K.S., Guo, B., Kappes, M.A., Opriessnig, T. 2012. Genetic and phenotypic characterization of a 2006 United States porcine reproductive and respiratory virus isolate associated with high morbidity and mortality in the field. Virus Research. 163(1):98-107. 23. Gauger, P.C., Zhang, J., Vincent, A.L. 2012. Flu virus continues to evolve in swine. National Hog Farmer. Available: http://nationalhogfarmer.com/health/flu-virus- continues-evolve-swine. 24. Godden, S.M., Smolenski, D.J., Donahue, M., Oakes, J.M., Bey, R., Wells, S., Sreevatsan, S., Stabel, J.R., Fetrow, J. 2012. Heat-treated colostrum and reduced morbidity in preweaned dairy calves: Results of a randomized trial and examination of mechanisms of effectiveness. Journal of Dairy Science. 95:4029-4040. 25. Greenlee, J.J., Nicholson, E.M., Smith, J.D., Kunkle, R.A., Hamir, A.N. 2012. Susceptibility of cattle to the agent of chronic wasting disease from elk after intracranial inoculation. Journal of Veterinary Diagnostic Investigation. 24(6):1087-1093.

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26. Greenlee, J.J., Smith, J.D., West Greenlee, M.H., Nicholson, E.M. 2012. Clinical and pathologic features of H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism. PLoS ONE. 7(6):e38678. 27. Greenlee, J.J., Zhang, Xia, Nicholson, E.M., Kunkle, R.A., Hamir, A.N. 2012. Prolonged incubation time in sheep with prion protein containing lysine at position 171. Journal of Veterinary Diagnostic Investigation. 24(3):554-558. 28. Hailat, N., Hemida, H., Hananeh, W., Stabel, J.R., Rezig, F., Jaradat, S., Al-Saleh, A. 2012. Investigation on the occurrence and pathology of paratuberculosis (Johne's disease) in apparently healthy cattle in Jordan. Comparative Clinical Pathology. 21(5):879-888. 29. Hessman, B.E., Sjeklocha, D.B., Fulton, R.W., Ridpath, J.F., Johnson, B.J., McElroy, D.R. 2012. Acute bovine viral diarrhea associated with extensive mucosal lesions, high morbidity, and mortality in a commercial feedlot. Journal of Veterinary Diagnostic Investigation. 24(2):397-404. 30. Kappes, M.A., Sandbulte, M.R., Platt, R., Wang, C., Lager, K.M., Henningson, J.N., Lorusso, A., Vincent, A.L., Loving, C.L., Roth, J.A., Kehrli Jr, M.E. 2012. Vaccination with NS1-truncated H3N2 swine influenza virus primes T cells and confers cross- protection against an H1N1 heterosubtypic challenge in pigs. Vaccine. 30(2):280-288. 31. Killian, M.L., Swenson, S.L., Vincent, A.L., Landgraf, J.G., Shu, B., Lindstrom, S., Xu, X., Klimov, A., Zhang, Y., Bowman, A.S. 2012. Simultaneous infection of pigs and people with triple reassortant swine influenza virus H1N1 at a U.S. county fair. Zoonoses and Public Health. Article published online: 9 JUL 2012 DOI: 10.1111/j.1863-2378.2012.01508.x 32. Kitikoon, P., Vincent, A.L., Gauger, P.C., Schlink, S.N., Bayles, D.O., Gramer, M.R., Darnell, D., Webby, R.J., Lager, K.M., Swenson, S.L., Klimov, A. 2012. Pathogenicity and transmission in pigs of the novel A(H3N2)v influenza virus isolated from humans and characterization of swine H3N2 viruses isolated in 2010-2011. Journal of Virology. 86(12):6804-6814. 33. Kudva, I.T. 2012. In vitro adherence patterns of Shigella serogroups to bovine rectoanal junction squamous epithelial (RSE) cells are similar to those of Escherichia coli O157. Foodborne Pathogens and Disease. 9(4):346-351. 34. Kudva, I.T., Davis, M.A., Griffin, R.W., Garren, J., Murray, M., John, M., Hovde, C.J., Calderwood, S.B. 2012. Polymorphic amplified typing sequences (PATS) and pulsed- field gel electrophoresis (PFGE) yield comparable results in the strain typing of a diverse set of bovine Escherichia coli O157 isolates. International Research Journal of Microbiology [serial online]. doi:10.1155/2012/140105 35. Kudva, I.T., Griffin, R.W., Krastins, B., Sarracino, D.A., Calderwood, S.B., Manohar, J. 2012. Proteins other than the Locus of Enterocyte Effacement-encoded proteins may contribute to Escherichia coli O157:H7 adherence to bovine rectoanal junction stratified squamous epithelial cells. BMC Microbiology. 12(103 36. Lager, K.M., Ng, T.F., Bayles, D.O., Alt, D.P., Delwart, E.L., Cheung, A.K. 2012.

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Diversity of viruses detected by deep sequencing in pigs from a common background. Journal of Veterinary Diagnostic Investigation. 24(6):1177-1179. 37. Lamont, E.A., Bannantine, J.P., Armien, A., Ariyakumar, D.S., Sreevatsan, S. 2012. Identification and characterization of a spore-like morphotype in chronically starved Mycobacterium avium subsp. paratuberculosis cultures. PLoS One [serial online]. 7(1):e30648. 38. Leite, F., Stabel, J.R. 2012. Comparison of fecal DNA extraction kits for the detection of Mycobacterium avium subsp. paratuberculosis. In: Proceedings of the 11th International Colloquium on Paratuberculosis, February 5-10, 2012, Sydney, Australia. p. 82-85. 39. Levine, U.Y., Bearson, S.M., Stanton, T.B. 2012. Mitsuokella jalaludinii inhibits growth of Salmonella enterica serovar Typhimurium. Veterinary Microbiology 159(1- 2):115-22. doi: 10.1016/j.vetmic.2012.03.027. Epub 2012 Mar 27. 40. Levine, U.Y., Stanton, T.B. 2012. Poultry intestinal microbiota (turkeys; chickens) - animal health and food safety perspectives. Encyclopedia of Metagenomics [serial online]. Available: http://www.springerreference.com/docs/html/chapterdbid/303274.html. 41. Looft, T.P., Allen, H.K. 2012. Collateral effects of antibiotics on mammalian gut microbiomes. Gut Microbes. 3(5):1-5. 42. Looft, T.P., Johnson, T., Allen, H.K., Bayles, D.O., Alt, D.P., Cole, J., Hashsham, S., Stedtfeld, R., Stedtfeld, T., Chai, B., Tiedje, J., Stanton, T.B. 2012. In-feed antibiotic effects on the swine intestinal microbiome. Proceedings of the National Academy of Sciences. 109(5):1691-1696. 43. Looft, T.P., Levine, U.Y., Stanton, T.B. 2012. Cloacibacillus porcorum sp. nov.,-a mucindegrading bacterium from the swine intestinal tract. International Journal of Systematic and Evolutionary Microbiology. 44. Loving, C.L., Vincent, A.L., Pena, L., Perez, D.R. 2012. Heightened adaptive immune responses following vaccination with a temperature-sensitive, live-attenuated influenza virus compared to adjuvanted, whole-inactivated virus in pigs. Vaccine. 30(40):5830- 5838. 45. Lu, Z., Zhang, J., Huang, C.M., Go, Y.Y., Faaberg, K.S., Rowland, R.R., Timoney, P.J., Balasuriya, U.B. 2012. Chimeric viruses containing the N terminal ectodomains of GP5 and M proteins of porcine reproductive and respiratory syndrome virus do not change the cellular tropism of equine arteritis virus. Virology. 432(1):99-109. 46. Lyashchenko, K.P., Greenwald, R., Esfandiari, J., Lecu, A., Waters, W.R., Posthaus, H., Bodmer, T., Janssens, J., Aloisio, F., Graubner, C., Grosclaude, E., Piersigilli, A., Schiller, I. 2012. Pulmonary disease due to Mycobacterium tuberculosis in a horse: zoonotic concerns and limitations of antemortem testing. Veterinary Medicine International [serial online].2012:Article 642145. 47. Lyashchenko, K.P., Greenwald, R., Esfandiari, J., Mikota, S., Miller, M., Moller, T.,

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Vogelnest, L., Gairhe, K.P., Robbe-Austerman, S., Gai, J., Waters, W.R. 2012. Field application of serodiagnostics to identify elephants with Tuberculosis prior to case confirmation by culture. Clinical and Vaccine Immunology. 19(8):1269-1275. 48. Miller, L.C., Fleming, D., Arbogast, A., Bayles, D.O., Guo, B., Lager, K.M., Henningson, J.N., Schlink, S.N., Yang, H.-C., Faaberg, K.S., Kehrli, Jr., M.E. 2012. Analysis of the swine tracheobronchial lymph node transcriptomic response to infection with a Chinese highly pathogenic strain of porcine reproductive and respiratory syndrome virus. BioMed Central (BMC) Veterinary Research. 8:208. Available: http://www.biomedcentral.com/1746-6148/8/208. 49. Montaldo, H.H., Casas, E., Sterman Ferraz, J.B., Vega-Murillo, V.E., Roman-Ponce, S.I. 2012. Opportunities and challenges from the use of genomic selection for beef cattle breeding in Latin America. Animal Frontiers. 2(1):23-29. 50. Nan, Y., Wang, R., Shen, M., Faaberg, K.S., Samal, S.K., Zhang, Y.J. 2012. Induction of type I interferons by a novel porcine reproductive and respiratory syndrome virus isolate. Virology. 432(2):261-270. 51. Nelson, M.I., Detmer, S.E., Wentworth, D.E., Tan, Y., Schwartzbard, A., Halpin, R.A., Stockwell, T.B., Lin, X., Vincent, A.L., Gramer, M.R., Holmes, E.C. 2012. Genomic reassortment of influenza A virus in North American swine, 1998-2011. Journal of General Virology. 93(Pt 12):2584-2589. 52. Nelson, M.I., Gramer, M.R., Vincent, A.L., Holmes, E.C. 2012. Global transmission of influenza viruses from humans to swine. Journal of General Virology. 93(10):2195- 2203. 53. Nelson, C.D., Reinhardt, T.A., Lippolis, J.D., Sacco, R.E., Nonnecke, B.J. 2012. Vitamin D signaling in the bovine immune system: A model for understanding human vitamin D requirements. Nutrients. 4(3):181-196. 54. Nelson, M.I., Vincent, A.L., Kitikoon, P., Holmes, E.C., Gramer, M.R. 2012. The evolution of novel reassortant A/H3N2 influenza viruses in North American swine and humans, 2009-2011. Journal of Virology. 86(16):8872-8878. 55. Nicholson, T.L., Brockmeier, S.L., Loving, C.L., Register, K.B., Kehrli, Jr., M.E., Stibitz, S.E., Shore, S.M. 2012. Phenotypic modulation of the virulent Bvg phase is not required for pathogenesis and transmission of Bordetella bronchiseptica in swine. Infection and Immunity. 80(3):1025-1036. 56. Nonnecke, B.J., Waters, W.R., Goff, J.P., Foote, M.R. 2012. Adaptive immunity in the colostrumdeprived calf: Response to early vaccination with Mycobacterium bovis strain bacille Calmette Guerin and ovalbumin. Journal of Dairy Science. 95(1):221-239. 57. Olsen, S.C., Johnson, C.S. 2012. Immune responses and safety after dart or booster vaccination of bison with Brucella abortus strain RB51. Clinical and Vaccine Immunology. 19(5):642-648. 58. Olsen, S.C., Bellaire, B., Roop II, R.M., Thoen, C.O. 2012. Brucella. In: Gyles, C.L., Prescott, J.F., Songer, J.G., Thoen, C.O., editors. Pathogenesis of Bacterial Infections in

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Animals. 4th edition. Hoboken, N.J.: Wiley-Blackwell. p. 429-441. 59. Olsen, S.C., Garin-Bastuji, B., Blasco, J.M., Nicola, A.M., Samartino, L. 2012. Brucellosis. In: Zimmerman, J.J., Karriker, L.A., Ramirez, A., Schwartz, K.J., Stevenson, G.W., editors. Diseases of Swine. 10th edition. Hoboken, N.J.: Wiley- Blackwell. p. 697-708. 60. Olsen, S.C., Johnson, C.S. 2012. Efficacy of dart or booster vaccination with strain RB51 in protecting bison against experimental Brucella abortus challenge. Clinical and Vaccine Immunology. 19(6):886-890. 61. Opriessnig, T., Gauger, P.C., Faaberg, K.S., Shen, H., Beach, N.M., Meng, X., Wang, C., Halbur, P.G. 2012. Effect of porcine circovirus type 2a or 2b on infection kinetics and pathogenicity of two genetically divergent strains of porcine reproductive and respiratory syndrome virus in the conventional pig model. Veterinary Microbiology. 158(1-2):69-81. 62. Osman, M.A., Stabel, J.R., Hostetter, J.M., Nettleton, D., Ware, D., Beitz, C.D. 2012. The other way around: probiotic Lactobacillus acidophilus NP51 restrict progression of Mycobacterium avium subspecies paratuberculosis (MAP) infection in Balb/c mice via activiation of CD8 alpha+ immune cell-mediated immunity. In: Proceedings of the 11th International Colloquium on Paratuberculosis, February 5-10, 2012, Sydney, Australia. p. 129-131. 63. Osman, M., Stabel, J.R., Onda, K., Dowd, S., Kreikemeier, W., Ware, D., Beitz, D.C. 2012. Modification of digestive system microbiome of lactating dairy cows by feeding Bovamine: effect on ruminal fermentation. Iowa State University Animal Industry Report. A.S. Leaflet No. R2701. 2 p. 64. Palmer, M.V., Thacker, T.C., Waters, W.R., Gortazar, C., Corner, L.A. 2012. Mycobacterium bovis: a model pathogen at the interface of domestic livestock, wildlife, and humans. Veterinary Medicine International [serial online]. Article ID 236205. doi:10.1155/2012/236205 65. Pena, L., Vincent, A.L., Loving, C.L., Henningson, J.N., Lager, K.M., Perez, D.R. 2012. Straindependent effects of PB1-F2 of triple reassortant H3N2 influenza viruses in swine. Journal of General Virology. 93(10):2204-2214. 66. Pena, L., Vincent, A.L., Loving, C.L., Henningson, J.N., Lager, K.M., Lorusso, A., Perez, D.R. 2012. Restored PB1-F2 into the 2009 pandemic H1N1 influenza virus has minimal effects in swine. Journal of Virology. 86(10):5523-5532. 67. Register, K.B., Sukumar, N., Palavecino, E.L., Rubin, B.K., Deora, R. 2012. Bordetella bronchiseptica in a paediatric cystic fibrosis patient: possible transmission from a household cat. Zoonoses and Public Health. 59(4):246-250. 68. Reinhardt, T.A., Lippolis, J.D., Nonnecke, B.J., Sacco, R.E. 2012. Bovine milk exosome proteome. Journal of Proteomics. 75(5):1486-1492. 69. Richeson, J.T., Kegley, E.B., Powell, J.G., Galloway, D.L., Hornsby, J.A., Schaut, R.G., Sacco, R.E., Ridpath, J.F. 2012. Weaning management of newly received beef

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calves with or without continuous exposure to a persistently infected bovine viral diarrhea virus pen mate: Effects on rectal temperature, peripheral blood leukocytes and serum proinflammatory cytokine and haptoglobin concentrations. Arkansas Animal Science Department Report 2011. AAES Research Series 597. p. 34-39. 70. Richeson, J.T., Kegley, E.B., Powell, J.G., Vander Ley, B.L., Ridpath, J.F. 2012. Weaning management of newly received beef calves with or without continuous exposure to a persistently infected bovine viral diarrhea virus pen mate: Effects on health, performance, bovine viral diarrhea virus titers, and peripheral blood leukocytes. Journal of Animal Science. 90:1972-1985. 71. Ridpath, J.F. 2012. Preventive strategy for BVDV infection in North America. In: Proceedings of the International Symposium on Worldwide Infectious Diseases of Farm Animal in Production Medicine; Prospective and Perspective, February 3-4, 2012, Hokkaido, Japan. Japanese Journal of Veterinary Research. 60(Supplement):S41-S49. 72. Ridpath, J.F., Neill, J.D., Chase, C.C. 2012. Impact of BVDV infection of white-tailed deer during second and third trimesters of pregnancy. Journal of Wildlife Diseases. 48(3):758-762 73. Sacco, R.E., Nonnecke, B.J., Palmer, M.V., Waters, W.R., Lippolis, J.D., Reinhardt, T.A. 2012. Differential expression of cytokines in response to respiratory syncytial virus infection of calves with high or low circulating 25-hydroxyvitamin D3. PLoS One. 7(3):e33074. 74. Sharma, V.K., Sacco, R.E., Kunkle, R.A., Bearson, S.M., Palmquist, D.E. 2012. Correlating levels of type III secretion and secreted proteins with fecal shedding of Escherichia coli O157:H7 in cattle. Infection and Immunity. 80(4):1333-1342. 75. Sinha, A., Schalk, S., Lager, K.M., Wang, C., Opriessnig, T. 2012. Singular PCV2a or PCV2b infection results in apoptosis of hepatocytes in clinically affected gnotobiotic pigs. Research in Veterinary Science. 92(1):151-156. 76. Smith, J.D., Greenlee, J.J., Foster, G.H., Nicholson, E.M. 2012. Acetone precipitation of the scrapie agent results in successful recovery of PrPSc but decreased infectivity. Journal of Agricultural and Food Chemistry. 60(18):4758-4762. 77. Stabel, J.R., Waters, W.R., Bannantine, J.P., Lyashchenko, K. 2012. Activation of host immune responses in neonatal calves and interference with TB diagnostics after immunization with a commercial heat-killed vaccine. In: Proceedings of 11th International Colloquium on Paratuberculosis, February 5-10, 2012, Sydney, Australia. p. 126-129. 78. Sun, X., Wertz, N., Lager, K., Sinkora, M., Stepanova, K., Tobin, Butler, J.E. 2012. Antibody repertoire development in fetal and neonatal piglets. XXII. Lambda rearrangement precedes kappa rearrangement during B-cell lymphogenesis in swine. Immunology. 137(2):149-159. 79. Sun, X.Z., Wertz, N., Lager, K.M., Tobin, G., Butler, J.E. 2012. Antibody repertoire development in fetal and neonatal piglets. XXIII: fetal piglets infected with a vaccine strain of PRRS virus display the same immune dysregulation seen in isolator piglets.

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Vaccine. 30(24):3646-3652. 80. Tamguney, G., Richt, J.A., Hamir, A.N., Greenlee, J.J., Miller, M.W., Wolfe, L.L., Sirochman, T.M., Young, A.J., Glidden, D.V., Johnson, N.L., Giles, K., Dearmond, S.J., Prusiner, S.B. 2012. Salivary prions in sheep and deer. Prion. 6(1):52-61. 81. Vander Ley, B.L., Ridpath, J.F., Sweiger, S.H. 2012. Bovine viral diarrhea virus antigen detection across whole cattle hides using two antigen-capture enzyme-linked immunoassays. Journal of Veterinary Diagnostic Investigation. 24(3):546-548. 82. Vincent, A.L., Kitikoon, P., Gauger, P.C., Gramer, M.R., Lorusso, A., Lager, K.M., Ciacci-Zanella, J.R. 2012. Global coordination for swine influenza virus surveillance and research: what are we missing from the big picture? In: Proceedings of the 43rd American Association of Swine Veterinarians Annual Meeting, March 10-13, 2012, Denver, Colorado. p. 507-512. 83. Vincent, A.L., Ma, W., Lager, K.M., Richt, J.A., Janke, B.H., Sandbulte, M.R., Gauger, P.C., Loving, C.L., Webby, R.J., García-Sastre, A. 2012. Live attenuated influenza vaccine provides superior protection from heterologous infection in pigs with maternal antibodies without inducing vaccine associated enhanced respiratory disease. Journal of Virology. 86(19):10597-10605. 84. Vrentas, C.E., Greenlee, J.J., Tatum, T.L., Nicholson, E.M. 2012. Relationships between PrPSc stability and incubation time for United States scrapie isolates in a natural host system. PLoS ONE. 7(8):e43060. 85. Vrentas, C.E., Onstot, S., Nicholson, E.M. 2012. A comparative analysis of rapid methods for purification and refolding of recombinant bovine prion protein. Protein Expression and Purification. 82(2):380-388. 86. Wadhwa, A., Bannantine, J.P., Byrem, T., Stein, T.L., Saxton, A.M., Speer, C.A., Eda, S. 2012. Optimization of serum EVELISA for milk testing of Johne's disease. Foodborne Pathogens and Disease. 9(8):749-754. 87. Waters, W.R. 2012. Bovine TB and the 'singleton protocol': reward without risk. Veterinary Record. 2012(170):514-515. 88. Waters, W.R., Palmer, M.V., Buddle, B.M., Vordermeier, H.M. 2012. Bovine tuberculosis vaccine research: historical perspectives and recent advances. Vaccine. 30(16):2611-2622. 89. Waters, W.R., Thacker, T.C., Nonnecke, B.J., Palmer, M.V., Schiller, I., Oesch, B., Vordermeier, H.M., Silva, E., Estes, D.M. 2012. Evaluation of gamma interferon (IFN- gamma)-induced protein 10 responses for detection of cattle infected with Mycobacterium bovis: comparisons to IFN-gamma responses. Clinical and Vaccine Immunology. 19(3):346-351. 90. Wilson, R., Plinston, C., Hunter, N., Casalone, C., Corona, C., Tagliavini, F., Suardi, S., Ruggerone, M., Moda, F., Graziano, S., Sbriccoli, M., Cardone, F., Pocchiari, M., Ingrosso, L., Baron, T., Richt, J., Andreoletti, O., Simmons, M., Lockey, R., Manson, J.C., Barron, R.M. 2012. Chronic wasting disease and atypical forms of bovine

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spongiform encephalopathy and scrapie are not transmissible to mice expressing wild- type levels of human prion protein. Journal of General Virology. 93(Pt 7):1624-1629. 91. Zanella, E.L., Miller, L.C., Lager, K.M., Bigelow, T.T. 2012. Evaluation of a real-time polymerase chain reaction assay for pseudorabies virus surveillance purposes. Journal of Veterinary Diagnostic Investigation. 24(4):739-745. 92. Zehr, E.S., Lavrov, D.V., Tabatabai, L.B. 2012. Comparison of Haemophilus parasuis reference strains and field isolates by using random amplified polymorphic DNA and protein profiles. BMC Microbiology. doi:10.1186/1471-2180-12-108. 93. Zeng, X., Wei, Y., Huang, J., Newell, E.W., Yu, H., Kidd, B.A., Kuhns, M.S., Waters, W.R., Davis, M.M., Weaver, C.T., Chien, Y. 2012. Gamma delta T cells recognize a microbial encoded B Cell antigen to initiate a rapid antigen-specific Interleukin-17 response. Immunity. 37(3):524-534.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: Provide scientific information to solutions in the control and eradication of national and international exotic, emerging, zoonotic, and endemic infectious diseases of animals through a comprehensive research program emphasizing basic and applied research in diagnostics, prevention, and control strategies, prediction of disease outbreaks, molecular epidemiology, and understanding disease pathogenesis.

The objectives of the research programs are to produce new research knowledge and technology to:

 prevent, reduce or eliminate losses from impaired performance, and increased deaths and condemnations;  develop more sensitive, specific and faster diagnostic tests;  develop vaccines designed for the control and, when feasible, the eradication of disease;  improve our understanding of the ecology and epidemiology of pathogens at the domestic-wild life interface; and  improve our understanding of the genetic and pathobiological basis of virulence.

This research provides government regulatory agencies and the livestock industries with improved intervention strategies against priority diseases.

(ii) Agents Microorganisms and/or Toxins:

• Overlap Select Agents Including NIAID Category B Priority Pathogens

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• USDA Select Agents and Toxins • Other pathogens or toxins Including non-Select Agent, NIAID Category B and C Priority Pathogens

The agents studied are endemic and emerging viruses and bacteria that cause diseases in livestock and poultry. The majority of the agents studied are not classified by USDA as select agents. The agents classified as select agents are pathogens that are zoonotic agents (diseases transmitted from animals to people) that pose a threat to U.S. animal production systems, agricultural economy, and agricultural exports.

(iii) Outdoor Studies: No research work is done outdoors with infectious organisms. Outdoor studies are conducted only for ecological purposes and monitoring of bacteria, viruses, and prions in wildlife.

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Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Southeast Poultry Research Laboratory

2. Where is it located (provide both address and geographical location)?

Agricultural Research Service, United States Department of Agriculture 934 College Station Road

Athens, Georgia 30605

3. Floor area of laboratory areas by containment level:

BL2 1138 (sqM) BL3 624 (sqM) BL4 0 (sqM) Total laboratory floor area 1762 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 40

(ii) Division of personnel:

Military 0

Civilian 40

(iii) Division of personnel by category:

Scientists 11

Engineers 0

Technicians 16

Administrative and support staff 13

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Animal Science, Biochemistry, Biology, Biotechnology, Cell Biology, Clinical Immunology, Computational Biology, Genetics, Genomics, Immunology, Infectious

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Disease, Microbiology, Molecular Biology, Molecular Computational Biology, Pathogenesis, Pathology, Proteomics, Public Health, Statistics, Vaccine Evaluation, Veterinary Clinical Research, Veterinary Medicine, Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 3

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Agriculture (USDA) Centers for Disease Control and Prevention (CDC) U.S. Department of Defense (DOD) Non-profit Associations Private Sector Companies National Institutes of Health (NIH) U.S. Department of State Other Governmental Agencies

(vii) What are the funding levels for the following program areas:

Research $ 5,800,000 Development $ 0 Test and evaluation $ 0 Total $ 5,800,000

(viii) Briefly describe the publication policy of the facility:

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

1. Belser, J., Gustin, K.M., Maines, T.R., Pantin Jackwood, M.J., Katz, J.M., Tumpey, T.M. 2012. Influenza virus respiratory infection and transmission following ocular

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inoculation in ferrets. PLoS Pathogens. 8(3):e1002569. 2. Burand, J.P., Kim, W., Afonso, C.L., Tulman, E., Kutish, G.F., Rock, D.L. 2012. Analysis of the genome of the sexually transmitted insect virus Hz-2V. Viruses. 4(1):28-61. 3. Cilloniz, C., Pantin Jackwood, M.J., Ni, C., Carter, V.S., Korth, M.J., Swayne, D.E., Tumpey, T.M., Katze, M.G. 2012. Molecular signatures associated with Mx-1 mediated resistance to highly pathogenic influenza virus infections: mechanisms of survival. Journal of Virology. 86:2437-2446. 4. Courtney, S.C., Gomez, D., Killian, M.L., Pedersen, J.C., Miller, P.J., Afonso, C.L. 2012. Complete genome sequencing of a novel Newcastle disease virus isolate circulating in chicken layers in the Dominican Republic. Journal of Virology. 86(17):9550. 5. Day, J.M. 2012. Investigating the complex viral community of the turkey gut: an update from the laboratory and the field. North Carolina Turkey Industry Days Proceedings. Avian Diseases. 7:1-4. 6. Deng, Q., Song, M., Demers, A., Weng, Y., Lu, W., Wang, D., Kaushik, R.S., Yu, Q., Li, F. 2012. Biochemical characterization of the small hydrophobic protein of avian metapneumovirus. Virus Research. 167:297-301. 7. Diel, D.G., Da Silva, L.A., Liu, H., Wang, Z., Miller, P.J., Afonso, C.L. 2012. Genetic diversity of avian paramyxovirus type 1: Proposal for a unified nomenclature and classification system of Newcastle disease virus genotypes. Infection, Genetics and Evolution. 12(8):1770-1779. 8. Diel, D.G., Miller, P.J., Wolf, P.C., Mickley, R.M., Musante, A.R., Emanueli, D.C., Shively, K.J., Afonso, C.L. 2012. Characterization of Newcastle disease virus isolated from cormorant and gull species in the United States in 2010. Avian Diseases. 56:128- 133. 9. Diel, D.G., Susta, L., Cardenas, S., Brown, C.C., Miller, P.J., Afonso, C.L. 2012. Complete genome and clinic opathological characterization of a virulent Newcastle disease virus isolate from South America. Journal of Clinical Microbiology. 50:378- 387. 10. Edwards, I.C., Miller, P.J., Afonso, C.L. 2012. Characterization of the live LaSota- vaccine strain-induced protection in chickens upon early challenge with a virulent Newcastle disease virus of heterologous genotype. Avian Diseases. 56:464-470. 11. Gilbert, M., Jambal, L., Karesh, W., Dulam, P., Sodnomdarjaa, R., Tseveemyadag, N., Cardona, C., Leung, C., Peirs, M., Spackman, E., Swayne, D.E., Joly, D. 2012. Surveillance for highly pathogenic avian influenza virus among wild birds in Mongolia, 2005-2011. PLoS One. 7(9):e44097. 12. Hu, H., Zhao, W., Yu, Q. 2012. Avian metapneumovirus molecular biology and development of genetically engineered vaccines. China Poultry. 34(12):1-5. 13. Josset, L., Belser, J., Chang, J., Pantin Jackwood, M.J., Chang, S., Belisle, S., Tumpey,

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T.M., Katze, M.G. 2012. Implication of inflammatory macrophages, nuclear receptors and interferon regulatory factors in increased virulence of pandemic 2009 H1N1 influenza a virus after host adaptation. Journal of Virology. 86:7192-7206. 14. Kapczynski, D.R., Martin, A., Haddad, E.E., King, D.J. 2012. Protection from clinical disease against three highly virulent strains of Newcastle disease virus following in ovo application of an antibody-antigen complexed vaccine in maternally-antibody positive chickens. Avian Diseases. 56(3):555-560. 15. Ladman, B., Spackman, E., Gelb, J. 2012. Comparison of pooling eleven and five oropharyngeal swabbings for detecting avian influenza virus by real-time RT-PCR in broiler chickens. Avian Diseases. 56(1):227-229. 16. Pantin Jackwood, M.J., Smith, D.M., Wasilenko, J.L., Spackman, E.V. 2012. Low pathogenicity avian influenza viruses infect chicken layers by different routes of inoculation. Avian Diseases. 56:276-281. 17. Pantin Jackwood, M.J., Todd, D., Koci, M.D. 2012. Avian Astrovirus. In: Schultz- Cherry, S., editor. Astrovirus Research. Book Chapter. p.151-180.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms4 and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: Provide scientific solutions to national and international exotic, emerging and endemic poultry viral diseases through a comprehensive research program emphasizing basic and applied research in diagnostics, prevention, and control strategies, prediction of disease outbreaks, molecular epidemiology, and understanding disease pathogenesis.

The objectives of the research program are to produce new research knowledge and technology to:

 prevent, reduce or eliminate losses from impaired performance and increased deaths and condemnations;  develop more sensitive, specific and faster diagnostic tests;

 develop vaccines designed for the control and, when feasible, the eradication of disease;  improve our understanding of the ecology and epidemiology of viruses at the wild bird-domestic poultry interface; and  improve our understanding of the genetic and pathobiological basis of virulence.

This research provides government regulatory agencies and the poultry industries with improved intervention strategies against poultry viral diseases. The Laboratory has two research units: 1) Exotic and Emerging Avian Viral Diseases Research Unit, and 2) Endemic Poultry Viral Diseases Research Unit.

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(ii) Agents Microorganisms and/or Toxins:

• USDA Select Agents and Toxins • Other pathogens or toxins Including non-Select Agent, NIAID Category B and C Priority Pathogens

The agents studied are foreign and emerging viruses that cause diseases in poultry. The majority of the agents studied are classified by USDA as select agents. Some of the agents classified as select agents are pathogens that are zoonotic agents (diseases transmitted from animals to people) that pose a threat to our poultry production systems, our agricultural economy, and agricultural exports.

(iii) Outdoor Studies: No research work is done outdoors with infectious organisms. Outdoor studies are conducted only for ecological purposes and monitoring of viruses in free flying wild birds.

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Form B

BWC - Confidence Building Measure

Exchange of information on outbreaks of infectious diseases and similar occurrences caused by toxins

United States of America

April 15, 2013

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Form B

Information on outbreaks of infectious diseases and similar occurrences, that seem to deviate from the normal pattern5

1. Time of cognizance of the outbreak The notification of a cluster of suspected fungal endophthalmitis cases in Los Angeles County was reported to CDC on March 6th.

2. Location and approximate area affected Nine states reported cases that met the outbreak case definition; however, product from the implicated pharmacy was shipped to all 50 states as well as internationally.

3. Type of disease/intoxication Fungal endophthalmitis

4. Suspected source of disease/intoxication Two products labeled as sterile from a single pharmacy: Brilliant Blue-G dye and triamcinolone acetate.

5. Possible causative agent(s) Fusarium incarnatum-equiseti species complex and Bipolaris hawaiiensis

6. Main characteristics of systems Endophthalmitis - affecting the anterior and posterior chambers of the eye

7. Detailed symptoms, when applicable Pain, decreased visual acuity, floaters

8. Deviation(s) from the normal pattern as regards type, etc. Multiple cases of fungal endophthalmitis in multiple facilities (e.g. outbreak vs. sporadic cases), subacute onset of illness, waxing and waning symptoms

9. Approximate number of primary cases 47

10. Approximate number of total cases 47

11. Number of deaths none

5 See paragraph 2 of the chapeau to Confidence-Building Measure B. Page 189 of 237

12. Development of the outbreak Cases were initially discovered at a single ambulatory surgical center in Los Angeles County and associated with Brilliant Blue-G dye. Subsequent cases were found in Nevada, Indiana, Louisiana, Colorado and Texas for a total of 21 cases of fungal endophthalmitis in this culture. During the investigation into Brilliant Blue-G dye, CDC was notified of

another cluster of cases of fungal endophthalmitis in persons exposed to triamcinolone acetate from the same pharmacy. Eventually we identified 26 cases in New York, California, Illinois, and North Carolina in this second cluster.

13. Measures taken March 9, 2012 - Implicated pharmacy recalled all Brilliant Blue-G lots. March 31st - Implicated pharmacy recalled one lot of triamcinolone acetate. Multiple dates - state boards of pharmacy in CA, LA, and NY issued cease/desist orders blocking shipments of the implicated pharmacy products. May 3rd - CDC released an MMWR publishing the name of the pharmacy and advising against use of any sterile compounded products from the company. Multiple dates - Epi-X, FDA medwatch, professional society emails sent /posted to publicize the outbreak and find cases. May 24th - Implicated pharmacy recalled all sterile compounded products produced over the past 6 months. Multiple dates - FDA conducted an investigation and environmental sampling of the implicated pharmacy. July 2012 - Implicated pharmacy suspends sterile compounding operations and closes its operation.

Form B

Information on outbreaks of infectious diseases and similar occurrences, that seem to deviate from the normal pattern5

1. Time of cognizance of the outbreak 07/20/2012

2. Location and approximate area affected Ill cases were distributed across the United States, in 13 states total plus the District of Columbia.

3. Type of disease/intoxication Invasive infection with a rare bacterial strain of Listeria monocytogenes.

4. Suspected source of disease/intoxication Imported Italian Frescolina Marte brand ricotta salata cheese

5. Possible causative agent(s) Listeria monocytogenes serotype 1/2a

6. Main characteristics of systems

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Listeriosis is a life-threatening infection caused by eating food contaminated with the bacterium Listeria monocytogenes. The disease primarily affects pregnant women, persons with weakened immune systems, and older adults. Rarely, persons without these risk factors can be affected. A person with listeriosis usually has fever and muscle aches, often preceded by diarrhea or other gastrointestinal symptoms. Almost everyone who is diagnosed with listeriosis has invasive infection.

7. Detailed symptoms, when applicable Twenty ill persons were hospitalized. Nine of the illnesses were related to pregnancy; three of these were diagnosed in newborns. The other 13 ill persons ranged in age from 30 years to 87 years, with a median age of 77 years, and 54% were female. Eleven patients had bacteremia, 3 had meningitis, and 2 patients reported flu-like symptoms.

8. Deviation(s) from the normal pattern as regards type, etc. Public health investigators are using DNA "fingerprints" of Listeria obtained through diagnostic testing with pulsed-field gel electrophoresis, or PFGE, to identify cases of illness that may be part of this outbreak. They are using data from PulseNet, the national subtyping network made up of state and local public health laboratories and federal food regulatory laboratories that performs molecular surveillance of foodborne infections. Four PFGE patterns defined the "outbreak strain". The four PFGE patterns in this outbreak were all rare or new, and above baseline. All four PFGE patterns were indistinguishable by multiple- locus variable number tandem repeat analysis (MLVA). From an initial case-by-case analysis, we found a strong association between outbreak-associated listeriosis and consumption of any soft cheese (90% of cases vs. 37% of controls, mOR=17.3, 95% CI 2.0- 825.7, p=0.003). Data from a supplemental questionnaire focused on soft cheeses indicate that most patients purchased and consumed cut and repackaged cheeses. The outbreak strain was isolated from a total of 5 different cut and repackaged cheeses, including the implicated ricotta salata, as well as from cutting boards and knives at a distribution facility. The outbreak strain was isolated from intact wheels of the implicated ricotta salata. In addition, patients reported consuming a variety of different types and brands of cut and repackaged cheese. Only 7 patients reported exposure to the implicated cheese. These lines of evidence indicate that cross-contamination occurred through cutting and repackaging of cheeses.

9. Approximate number of primary cases 22

10. Approximate number of total cases 22

11. Number of deaths Four deaths were reported, one each from Minnesota, New York, Nebraska, and California. In Nebraska and California, public health officials determined that the deaths were related to listeriosis. In Minnesota and New York, public health officials did not report listeriosis as a cause of death because it was not listed as such on the death certificates. One fetal loss

Page 191 of 237

also was reported.

12. Development of the outbreak In interviews, ill persons answered questions about foods consumed and other exposures in the month before becoming ill. Twelve (80%) of 15 ill persons interviewed using the Listeria Initiative questionnaire reported consuming a soft cheese. Ten (91%) of 11 ill persons who could provide information about packaging of cheeses reported consuming cheese that had been cut and repackaged at a retail location. Seven cases were linked to consumption of Frescolina Marte brand ricotta salata. The investigation was complex because ill persons reported consuming many different cheese brands and types from many different retail locations. No one cheese was initially reported by the majority of ill persons,

suggesting that cross-contamination of other cheeses through cutting boards or utensils played a role. The investigation focused on identifying intact cheeses shipped to multiple retail locations where, in the cutting process, they could have cross-contaminated other cheeses purchased by ill persons. FDA isolated the outbreak strain of Listeria from a sample of uncut Frescolina Marte brand ricotta salata cheese, which was imported from Italy and distributed by Forever Cheese, Inc. The outbreak strain was also isolated from other types of soft cheese that had already been cut and repackaged.

13. Measures taken On September 10, 2012, Forever Cheese, Inc. initiated a voluntary recall of Frescolina Marte brand ricotta salata cheese with a single lot number and/or production code. On September 13, 2012, the U.S. Food and Drug Administration placed the exporter of the recalled cheese, Fattorie Chiarappa S.R.L. of Conversano, Italy, on Import Alert. This means that Fattorie Chiarappa cheese will be denied admission into the United States unless

the importer shows that the cheese product is not contaminated with Listeria. On September 14, 2012, Forever Cheese, Inc. issued an expanded recall of all lots and production codes of Frescolina Marte brand ricotta salata cheese and issued a market withdrawal of all cheeses they received that were produced by the Italian cheese exporter.

Form B

Information on outbreaks of infectious diseases and similar occurrences, that seem to deviate from the normal pattern5

1. Time of cognizance of the outbreak March 1, 2012

2. Location and approximate area affected Ill cases were distributed nationally across the United States, in 28 states total plus the District of Columbia. Cases were concentrated along the eastern coast.

3. Type of disease/intoxication

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Bacterial

4. Suspected source of disease/intoxication Frozen raw yellowfin tuna product, known as Nakaochi Scrape, from Moon Marine USA Corporation.

5. Possible causative agent(s) Infection with a rare bacterial strain of Salmonella enterica serotype Bareilly or Salmonella enterica serotype Nchanga

6. Main characteristics of systems Most persons infected with Salmonella bacteria develop diarrhea, fever, and abdominal cramps 12 to 72 hours after infection. The illness usually lasts 4 to 7 days, and most persons recover without treatment. However, in some persons, diarrhea may be so severe that the patient needs to be hospitalized.

7. Detailed symptoms, when applicable Among 326 persons with available information, 55 (17%) reported being hospitalized. No deaths were reported.

8. Deviation(s) from the normal pattern as regards Salmonella Bareilly and Salmonella Nchanga are unusual serotypes of Salmonella in the United States

9. Approximate number of primary cases 425

10. Approximate number of total cases 425

11. Number of deaths 0

12. Development of the outbreak New York State Department of Health initially notified CDC's Outbreak Response Team of a cluster of 4 ill persons infected with Salmonella Bareilly with the same unusual pulsed- field gel electrophoresis pattern. Subsequent cases were identified throughout the United States, with the majority of cases concentrated along the eastern coast. A total of 425 persons infected with the outbreak strains of Salmonella Bareilly or Salmonella Nchanga were reported from 28 states and the District of Columbia. Collaborative investigation efforts of state, local, and federal public health agencies linked this outbreak to a frozen raw yellowfin tuna product, known as Nakaochi Scrape, from Moon Marine USA Corporation.

13. Measures taken

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On April 13, 2012, Moon Marine USA Corporation of Cupertino, California voluntarily recalled 58,828 pounds of a frozen raw yellowfin tuna product, labeled as Nakaochi Scrape AA or AAA. A Seafood Hazard Analysis and Critical Control Point (HACCP) inspection was conducted by FDA April 19-24, 2012 at the Moon Fishery Pvt Ltd. processing facility in Aroor, India. Based on the initial tour of the facility, inspectors identified several seafood HACCP deficiencies, such as lack of controls for histamine at receipt of product, lack of

controls for Clostridium botulinum at storage, and several significant sanitation observations of concern. On May 10, 2012, Moon Fishery (India) Pvt. Ltd., the manufacturer of the frozen yellowfin tuna Nakaochi Scrape, expanded the voluntary recall to include its 22-pound boxes of "Tuna Strips", Product of India, marked as "AA" or "AAA Grade."

Form B

Information on outbreaks of infectious diseases and similar occurrences, that seem to deviate from the normal pattern5

1. Time of cognizance of the outbreak March 29, 2012 (first case identified in 2012)

2. Location and approximate area affected Multiple states: Hawaii (1 case), Indiana (5 cases), Minnesota (3 cases), Missouri (1 case), Ohio (10 cases), Utah (1 case)

3. Type of disease/intoxication Influenza virus respiratory infection

4. Suspected source of disease/intoxication Contact with infected swine

5. Possible causative agent(s) Influenza A H3N2v virus

6. Main characteristics of systems After an incubation period of 1-4 days, patients develop fever, myalgia, malaise, nonproductive cough, chills and headache. May progress to primary viral pneumonia in

some cases.

7. Detailed symptoms, when applicable Patients presented with fever and cough similar to seasonal influenza

8. Deviation(s) from the normal pattern as regards

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Infection with novel, swine-origin influenza A virus is sporadic in the U.S. and usually attributable to exposure to infected swine. Limited cases of person-to-person transmission have been found but no sustained transmission has been seen. (For more information, see http://www.cdc.gov/flu/swineflu/variant.htm)

9. Approximate number of primary cases 21

10. Approximate number of total cases 21

11. Number of deaths 0

12. Development of the outbreak Utah: On March 28, 2012, a four-year-old female became ill with measured fever of 105°F. The patient sought care at an emergency department on March 29, 2012, where a respiratory specimen was collected for influenza testing. The child was prescribed oseltamivir, discharged home, and has fully recovered from her illness. The specimen was positive for influenza and was sent to the Utah State Department of Health as part of routine influenza surveillance. RT-PCR testing indicated a possible influenza A (H3N2)v virus, and the sample was forwarded to CDC for additional testing. On April 6, 2012, partial genome sequencing confirmed influenza A (H3N2)v virus with the M gene from the influenza A (H1N1)pdm09 virus, similar to 12 cases detected in United States during August through December 2011. The patient had contact with swine in the week preceding illness.

Hawaii: On July 9, 2012, a patient developed fever and worsening cough. A respiratory specimen was collected on July 12, 2012, and was positive for influenza A. The specimen was forwarded to the State Laboratories Division, Hawaii Department of Health as part of routine influenza surveillance. RT-PCR testing on July 23, 2012 indicated a suspect

influenza A (H3N2) variant virus and the samples were forwarded to CDC for additional testing. On July 27, 2012, CDC confirmed Influenza A (H3N2)v virus with the M gene from the influenza A (H1N1)pdm09 virus.

Indiana: On July 26, 2012, one person became ill and sought care at a local healthcare provider on July 27, 2012. As part of an ongoing investigation into reported illness in swine and human attendees at several local county fairs, a respiratory specimen was collected from this patient on July 27, 2012 for influenza testing. RT-PCR testing conducted at the Indiana State Department of Health Laboratory indicated a probable influenza A (H3N2)v virus, and the sample was forwarded to CDC for additional testing. On August 1, 2012, CDC confirmed Influenza A (H3N2)v virus with the M gene from the influenza A (H1N1)pdm09 virus in these specimens. These viruses are similar to H3N2v cases detected previously in 2011 and 2012 in the United States. This case reported direct contact with ill swine in the week preceding illness. The person was not hospitalized and recovered from

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Ohio: Between July 24 and 28, 2012, 10 patients who attended a local fair in Ohio developed influenza-like illness. Respiratory specimens were collected from these patients as part of an investigation into reported illness in swine and human attendees of the fair held from July 22 -28, 2012, and were forwarded to the Ohio Department of Health Laboratory. RT-PCR testing on July 28, 2012, indicated probable influenza A (H3N2) variant virus, and the samples were forwarded to CDC for additional testing. On August 1, 2012, CDC confirmed Influenza A (H3N2)v virus with the M gene from the influenza A (H1N1)pdm09 virus in these specimens. These viruses are similar to H3N2v cases detected previously in 2011 and 2012 in the United States. No patients were hospitalized, and all patients recovered. All patients reported contact with swine in the week prior to illness onset.

Indiana: On July 12, 2012, two people developed respiratory symptoms and sought care at a local emergency department. Both reported contact with swine they exhibited at a local county fair. An investigation of reported illness in swine and humans that attended the fair identified two additional symptomatic people. Respiratory specimens were collected from these four persons on July 16, 2012. RT-PCR testing conducted at the Indiana State Department of Health Laboratory indicated a possible influenza A (H3N2) variant virus, (H3N2v) and the samples were forwarded to CDC for additional testing. On July 21, 2012, CDC confirmed influenza A in all four samples using RT-PCR, and partial genome sequencing of the viruses detected the presence of influenza H3N2v virus with the M gene from the influenza A (H1N1)pdm09 virus. Specimens were collected from 12 swine at the same fair and all were positive for influenza A (H3N2). Additional testing to assess the similarity between the swine and variant influenza viruses associated with this outbreak is ongoing. All four of the human cases reported direct contact with ill swine in the week preceding their illness onset. None of the patients were hospitalized, and all recovered from their illnesses.

Missouri: On August 12, 2012, a previously healthy adult female developed respiratory illness, and on August 16, she sought care from a physician who obtained a respiratory specimen for influenza diagnostic testing. The specimen was negative for influenza by rapid influenza diagnostic test on August 16, but was positive for influenza A subtype H1 at the Missouri State Public Health Laboratory; the sample was forwarded to CDC for additional testing. RT-PCR and genomic sequencing completed at CDC on September 11 indicated a triple-reassortant virus with 6 genes from classical swine influenza A (H1N1) and 2 genes from Influenza A (H1N1)pdm09 (PA and M genes). This is the same genome composition as an H1N1v virus identified in 2011 in a patient from Wisconsin; thus, this is the second case of infection with an H1N1v virus with this genome composition identified in the United States. The individual had direct contact with swine and worked at the Missouri State Fair (August 9-19, 2012). The patient was not hospitalized and recovered from her illness. Although there were reports of ill swine at the fair, none were tested for influenza. Two other people with exposure to swine experienced illness, though neither had a positive result when tested for influenza by RT-PCR.

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Minnesota: On August 26, 2012, a previously healthy adult female experienced acute onset of respiratory illness after exhibiting swine at the Minnesota State Fair from August 21-24. A throat swab specimen was obtained on August 26 at the fair as part of a Minnesota Department of Health program of enhanced surveillance for variant influenza viruses among people visiting state and local fairs. On August 27 reverse-transcriptase polymerase chain reaction (RT-PCR) testing at the Minnesota State Public Health Laboratory (MSPHL) identified probable influenza A H1N2v virus. The patient did not seek medical care and recovered from her illness. The specimen was sent to CDC, and H1N2v virus with the matrix gene from the pdm09 H1N1 influenza virus was identified by genomic sequencing on August 31. Additionally, sequencing of H1N2 virus from swine sampled at the same location matched that of the human isolate. Two additional people with H1N2v virus infections were later confirmed. The first, a male child with asthma experienced influenza- like illness (ILI) on August 27. He reported direct, prolonged contact with swine at the Minnesota State Fair on August 24. The second, an elderly female with diabetes, experienced acute onset of ILI on August 26. She also reported direct, prolonged contact with swine at the Minnesota State Fair on August 24. She was admitted to the hospital on August 28 and discharged on August 31. Both individuals have recovered. RT-PCR testing by the MSPHL identified probable influenza H1N2v virus in specimens from both persons. Confirmatory testing at CDC on September 5 identified H1N2v with the matrix gene from the pdm09 H1N1 virus.

13. Measures taken Notifications to state and local public health departments requested enhanced surveillance to detect cases of influenza-like illness outside of the normal season with particular attention to patients having known exposure to swine. Clinicians were advised that licensed antiviral neuraminidase inhibitors such as oseltamivir are expected to be effective treatments. Notices were posted at agricultural fairs advising high-risk individuals to avoid

attendance at swine exhibit events. Educational collaborations with youth groups such as 4H clubs emphasize the potential risks of prolonged exposure to swine. Collaborations have been extended with USDA to enhance surveillance for swine influenza in U.S. swine herds to determine virus strains circulating.

Form B

Information on outbreaks of infectious diseases and similar occurrences, that seem to deviate from the normal pattern5

1. Time of cognizance of the outbreak Mid-July, 2012.

2. Location and approximate area affected Human West Nile Virus (WNV) cases were reported from all of the continental 48 states.

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Approximately 1/3 of total cases were reported from Texas. An additional 40% of the total cases were distributed among 10 states (CA, LA, IL, MS, SD, MI, OK, NE, CO, AZ). Within Texas, 50% of cases reported from Dallas, Tarrant, Collin and Denton counties.

3. Type of disease/intoxication West Nile Virus Neuroinvasive Disease (WNND) and West Nile Fever

4. Suspected source of disease/intoxication Infection with West Nile virus via bite of infected mosquito

5. Possible causative agent(s) West Nile Virus

6. Main characteristics of systems In neuroinvasive presentations: encephalitis, meningitis, acute flaccid paralysis

7. Detailed symptoms, when applicable In neuroinvasive presentations: encephalitis, meningitis, acute flaccid paralysis

8. Deviation(s) from the normal pattern as regards type, etc. By mid-July, case reports exceeded the numbers reported for the same time period since 2003, making 2012 the second-largest WNV outbreak in the U.S. at that early point in the transmission season. This trend continued through the end of 2012, with the number of WNND cases being the highest reported since 2003.

9. Approximate number of primary cases 5387 Total Cases

10. Approximate number of total cases 5387 Total Cases consisting of 2734 WNND and 2653 Fever cases reported as of December 11, 2012. In addition, 597 WNV viremic blood donors were detected in the national blood- donor screening program. Of these, 8 developed WNND and 86 developed West Nile Fever, and are included in the case report totals.

11. Number of deaths 243 deaths reported as of December 11, 2012

12. Development of the outbreak ArboNET is a passive electronic system managed by the Centers for Disease Control and Prevention (CDC). Arboviral surveillance data are reported to ArboNET by 50 state and three local or territorial health departments (New York City, the District of Columbia, and

Puerto Rico). Reporting jurisdictions receive data from public health and commercial reference laboratories, blood-collection agencies, and health-care providers. Jurisdictions

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transmit data to ArboNET using one of three methods: (1) uploading records from an existing electronic system using an Extensible Markup Language (XML) message, (2) uploading from a Microsoft® Access database using an XML message, or (3) entering records manually using a Web-based form. Data are summarized weekly, evaluated for trends compared to previous years, and distributed to state health department stakeholders. By mid-July 2012, case reports submitted to ArboNET indicated that WNV transmission activity was at levels similar to those observed during the large outbreak that occurred nationwide in 2003. From 2002 - 2011, an average of 2845 WNV disease cases per year (range = 663-8621) was reported. This included an average of 1,165 WNND cases and 1,680 non-neuroinvasive disease cases. From 2004-2011 (period for which data are available), an average of 221 WNV viremic blood donors per year (range = 109-395) was reported. The 5,387 human disease cases reported in 2012 is the highest number of cases reported since 2003.

13. Measures taken Local vector control agencies implemented enhanced adult mosquito control. Additional Federal funds provided to Texas Department of State Health Services to support diagnostic laboratory and vector control activities. Press releases with prevention (personal protection) messages were widely distributed throughout the region.

Form B

Information on outbreaks of infectious diseases and similar occurrences, that seem to deviate from the normal pattern5

There were four World Organization for Animal Health (OIE) immediate reports for animal disease events in 2012 (deviations from normal pattern), and three ongoing open reports from 2011. Event summaries can be found on the OIE website: http://web.oie.int/wahis/public.php?page=home.

Summary of Reports

1) ‘Atypical' bovine spongiform encephalopathy (BSE) (OIE Immediate Report June 15, 2012 - Resolved June 30, 2012). Bovine spongiform encephalopathy (BSE) is a fatal neurological disease of adult cattle that was first recognized in Great Britain (GB). It is a transmissible prion disease.

As part of the United States targeted bovine spongiform encephalopathy (BSE) surveillance system, a case of BSE classified as atypical was identified in a dead dairy cow that was to be rendered. An epidemiologic investigation of the event was conducted in accordance with the USDA's 2012 BSE Response Plan. The cow was culled due to lameness and testing results from immunohistochemistry and Western blot tests at USDA's National Veterinary Services Laboratories (NVSL) confirmed the animal positive for atypical BSE, a very rare form of the disease not generally associated with an animal consuming infected feed. The dead animal's

Page 199 of 237 carcass was destroyed. The identified animal was never presented for slaughter for human consumption, did not enter food supply channels, and so at no time did it present any risk to human health. The epidemiological investigation identified all at-risk cattle and cattle of interest in the index and all associated herds. Two offspring of the index animal were designated as at- risk cattle. One of the at-risk offspring was stillborn and the second offspring was traced and tested for BSE. Test results were negative. In conjunction with USDA's investigation, the U.S. Department of Health and Human Services' Food and Drug Administration (FDA) and the California Department of Food and Agriculture (CDFA) conducted an extensive feed investigation. Investigation indicated feed suppliers were in compliance with all FDA and CDFA regulations and requirements. The BSE event classified as Atypical is considered closed.

2) Vesicular Stomatitis Virus (OIE Immediate Report May 1, 2012 - Resolved December 27, 2012). Vesicular stomatitis (VS) is a vesicular disease of horses, cattle, and pigs caused by vesiculoviruses of the family Rhabdoviridae. This disease is clinically indistinguishable from foot-and-mouth disease (FMD), vesicular exanthema of swine (VES), or swine vesicular disease (SVD) when horses are not involved. Although VS may be suspected when horses are involved as well as pigs and cattle, prompt differential diagnosis is essential because the clinical signs of VS are indistinguishable from FMD when cattle and pigs are affected, and from SVD or VES when only pigs are affected.

On April 30, 2012, the National Veterinary Services Laboratories (NVSL) in Ames, Iowa, confirmed a finding of vesicular stomatitis virus (VSV) infection (New Jersey serotype) on an equine premises in Otero County, New Mexico. On August 1, 2012, the NVSL in Ames, Iowa, confirmed a finding of VSV infection (New Jersey serotype) on an equine premises in Las Animas County, Colorado. The USDA Animal Plant Health Inspection Service (APHIS) in conjunction with State animal health officials conducted comprehensive epidemiological investigations of the event. A total of 2 equine premises in 2 Colorado counties and 34 equine premises in 10 New Mexico counties were VSV-positive in 2012. All affected premises in both Colorado and New Mexico have been released from quarantine. All 2012 VSV cases were New Jersey serotype. The vesicular stomatitis event is considered closed.

3) Infection with Bonamia exitosa (OIE Immediate Report August 28, 2012 - Open). Bonamia exitiosa is a Haplosporidia protozoan parasite (Carnegie & Cochennec-Laureau, 2004) infecting haemocytes of several oyster species and inducing physiological disorders and eventually death of the animal (Cranfield et al., 2005; Dinamani et al., 1987).

Bonamia exitiosa was found infecting hatchery-produced C. virginica seed at 93.8% prevalence. No elevated mortality in the affected stock has been observed. C. virginica was thought to be refractory from B. exitiosa and the impact on production or wild populations of C. virginica is unknown. The farmed species were in open water with B. exitiosa susceptible wild species. Previous United States OIE reports indicating that B. exitiosa has “never occurred” in wild were in error. Improved resolution of Bonamia phylogeny allowed parasite infecting wild Ostrea equestris along the United States Southeastern coast to be identified as B. exitiosa. New diagnostics now allow B. exitiosa to be distinguished from other Bonamia species. The event is still open.

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4) White Spot Syndrome Virus (OIE Immediate Report June 18, 2012 - Resolved October 15, 2012). White spot syndrome virus (WSSV) is a Whispovirus of the family Nimaviridae that infects a wide range of aquatic crustaceans. Disease is predominately seen in shrimp and may include color change, the appearance of white spots, lethargy, and high mortality.

WSSV was detected on a shrimp farm on Oahu, Hawaii, during routine testing of broodstock shrimp as part of the Hawaii Department of Agriculture (HDOA) Shrimp Surveillance Certification Program (SSCP). At the time of sample collection, shrimp appeared stressed. All shrimp on the farm subsequently died. The HDOA placed a quarantine order on the movement of shrimp from the premises and a HDOA cleaning and disinfection (C&D) ‘premises clean-up plan' was implemented. The premises remains under a quarantine order, and removal of the quarantine is contingent upon the successful completion of the ’premises clean-up plan' requires additional C&D and surveillance prior to release of the quarantine. No more action in relation to the WSSV event is planned at the time of the report, and the WSSV event is considered closed.

5) White Spot Syndrome Virus (OIE Immediate Report October 24, 2011 - February 9, 2012). White spot syndrome virus (WSSV) is a Whispovirus of the family Nimaviridae that infects a wide range of aquatic crustaceans. Disease is predominately seen in shrimp and may include color change, the appearance of white spots, lethargy, and high mortality.

On October 13, 2011, the National Veterinary Services Laboratories (NVSL) confirmed white spot syndrome virus (WSSV) on a white legged meat shrimp farm on Kauai, Hawaii. A small increase in mortality was noticed in a few of the ponds at the meat production facility. The facility was placed under quarantine, all ponds were covered with nets, and affected ponds were harvested, dried, cleaned and disinfected (C&D). There are currently no clinical signs of WSSV including previously affected ponds that were restocked. The WSSV event is considered closed.

6) Contagious Equine Metritis (OIE Immediate Report July 27, 2011 - Resolved June 27, 2012). Contagious equine metritis is an inflammation of the endometrium of mares caused by Taylorella equigenitalis, which usually results in temporary infertility. It is a nonsystemic infection, the effects of which are restricted to the reproductive tract of the mare. Taylorella equigenitalis is most frequently transmitted by sexual contact with carrier stallions, which are always asymptomatic.

On July 21, 2011, a 4-year-old Arabian stallion in Arizona was confirmed positive for Taylorella equigenitalis, the bacterium that causes contagious equine metritis (CEM), during routine semen exportation screening. There is currently no known relationship between this CEM positive stallion and any other horses associated with previous U.S. cases of CEM. The epidemiological investigation identified 17 stallions and 13 mares that were potentially exposed to the infected stallion. All epidemiologically linked horses were identified and all testing and treatment protocols were completed in accordance with Federal, International, and expert guidance and requirements. All control, testing, and treatment measures that were implemented have been completed and are now closed. The comprehensive epidemiological investigation of this contagious equine metritis (CEM) event is closed.

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7) Equine piroplasmosis - Three OIE Ongoing Reports in 2012. Equine piroplasmosis is a tickborne protozoal disease of horses, mules, donkeys, and zebra. The aetiological agents are blood parasites named Theileria equi and Babesia caballi.

National Outbreak (2 ongoing OIE reports: T. equi and B. caballi): Testing for interstate movement and movement to equine events in response to the recent equine piroplasmosis (EP) outbreaks continues in many States. The USDA Animal Plant Health Inspection Service (APHIS) and the State Departments of Agriculture are conducting comprehensive epidemiological investigations of these events.

As of June 1, 2012, more than 178,589 U.S. horses were tested for equine piroplasmosis (T. equi and B. caballi) from November 2009 to 1 June 2012. As of June 1, 2012, 179 T. equi and 8 Babesia caballi-positive horses were detected in 21 States: AL, CA, CO, FL, GA, IL, IN, IA, KY, LA, MA, MI, MN, MS, NM, NC, OH, OK, SC, TN, and TX. Unlike the South Texas outbreak, transmission of the organism likely resulted from management practices (use of shared needles or substances between horses) rather than by a tick vector. Additionally, some of the EP-positive horses detected were imported prior to August 2005 when the official import test became the competitive enzyme-linked assay (cELISA). These imported horses are considered to have acquired their infections prior to arrival in the United States. Individual State movement testing for equine piroplasmosis continues in 2013.

South Texas Outbreak (Ongoing OIE report) Equine piroplasmosis (Theileria equi) was identified in South Texas on October 19, 2009. During the outbreak investigation, 2,500 horses were tested and 413 T. equi-positive horses were detected. T. equi-positive horses were identified in 17 States: AL, CA, CO, FL, GA, IN, LA, MN, MO, NM, NC, NJ, OK, TX, TN, UT, and WI. The T. equi-positive horses were either moved back to the index ranch in Texas to be managed under long-term quarantine, euthanized, or enrolled in research programs. Approximately 220 quarantined horses are undergoing treatment for research purposes. The results of the epidemiological investigation indicate that infection was likely present on the index ranch prior to 1990. Extensive tick studies on the index premises found one known experimental tick vector for T. equi, Dermacentor variablis, and determined via testing that a second tick species, Amblyomma cajennense, was also capable of transmitting T. equi. The epidemiological investigation has concluded for this outbreak but the OIE report is still open.

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Form C

BWC - Confidence Building Measure

Encouragement of Publication of Results and Promotion of Use of Knowledge

United States of America

April 15, 2013

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Form C

Encouragement of Publication of Results and Promotion of Use of Knowledge

U.S. Department of Health and Human Services (HHS) Open Government Plan and the HHS Strategic Plan 2010-2015

The U.S. Department of Health and Human Services (HHS) Open Government Plan represents the official response of the U.S. Department of Health and Human Services (HHS) to the White House's Open Government Directive, issued on December 8, 2009. The plan embraces the idea of working proactively and energetically to advance a culture of Open Government at HHS. HHS believes that transparency and data sharing are of fundamental importance to its ability to achieve its strategic goals of advancing the health and well-being of the United States. HHS's vast stores of data are a remarkable resource which can be utilized to help citizens understand what HHS does and hold it accountable, help the public hold the private sector accountable, increase awareness of health and human services issues, generate insights into how to improve health and well-being, spark public and private sector innovation and action, and provide the basis for new products and services. This plan also seeks to take Open Government to the next level by expanding opportunities for public participation in HHS activities and for collaboration across HHS and with the world outside HHS - especially via the use of new information and communications technologies. The HHS Open Government Plan is available online at: http://www.hhs.gov/open/plan/opengovernmentplan/openplanversion1_1.pdf, and HHS's Open Government Progress Report, highlighting some of the most important developments in HHS's Open Government Initiative, including Transparency and Data Sharing, is available at: http://www.hhs.gov/open/plan/june2011progressreport/index.html. The HHS Strategic Plan 2010-2015 describes HHS' work to address complex, multifaceted, and ever-evolving health and human service issues. Goal 4 of this plan is to Increase Efficiency, Transparency, and Accountability of HHS Programs. HHS embraces the power of Open Government, recognizing that with openness comes responsibility and accountability for results. Through Open Government, HHS is promoting transparency, participation, and collaboration – vital enablers of success in the HHS mission to improve the health and well-being of all Americans. HHS's Open Government efforts will break new ground in enabling the public to give feedback to HHS programs. HHS can help stakeholders contribute knowledge and experience to help it do jobs better, and HHS can support new kinds of collaborative teamwork that will deliver better results for our citizens. HHS will move forward toward new strategies, new tools, and a new culture of public participation and collaboration in its affairs. The HHS Strategic Plan is available as a web document at: http://www.hhs.gov/secretary/about/priorities/priorities.html

The Policy on Releasing and Sharing Data at the US Department of Health and Human Services (HHS) and its Components

There are a number of federally mandated regulations and clearance functions that affect the research and practice of HHS (for a list of HHS agencies and offices, please see: http://www.hhs.gov/about). They apply to all HHS employees, contractors, and awardees conducting data collection activities, whether the activities are for research or public health practice or occur in

Page 204 of 237 domestic or international settings. Examples include the HHS/FDA regulations for the protection of human research participants and compliance with the Federal Animal Welfare Act (AWA) as well as the Public Health Service Policy on Humane Care and Use of Laboratory Animals. In addition, the Paperwork Reduction Act (PRA), the Privacy Act, the Public Health Service Act (PHSA), the E- Government Act of 2002, the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule, and the Family Educational Rights and Privacy Act (FERPA) all include legislation or regulations that affect research and public health practice. HHS believes that public health and scientific advancement are best served when data are released to, or shared with, other public health agencies, academic researchers, and appropriate private researchers in an open, timely, and appropriate way. While recognizing the value of releasing data quickly and widely, HHS also considers the need to maintain high standards for data quality, the need for procedures that ensure that the privacy of individuals who provide personal information is not jeopardized, and the need to protect information relevant to national security, criminal investigations, or misconduct inquiries and investigations. The goal is to have a policy on data release and sharing that balances the desire to disseminate data as broadly as possible with the need to maintain high standards and protect sensitive information. Within this framework, specific HHS agencies and offices may have their own guidance for releasing and sharing data. The Centers for Disease Control (CDC) Policy on Releasing and Sharing Data is available online at: http://www.cdc.gov/maso/Policy/ReleasingData.pdf, and the National Institutes of Health (NIH) data Sharing Policy and Implementation Guide is available online at: http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm.

The Journal Emerging Infectious Diseases

This journal is published by the Centers for Disease Control and Prevention (CDC), and is ranked 5th out of 70 infectious disease journals. Emerging Infectious Diseases receives more than 1,800 manuscripts each year (most unsolicited, some invited) from authors around the world. It has 2500 subscribers to the print version in more than 100 countries and 66,000 subscribers to the electronic table of contents. The journal site receives hundreds of thousands of hits per month (CDC Web Statistics, http://wwwnc.cdc.gov/eid/pages/about.htm).

Emerging Infectious Diseases is available online at: http://wwwnc.cdc.gov/eid/.

The Morbidity and Mortality Weekly Report (MMWR) and Surveillance Summaries from the Centers for Disease Control and Prevention (CDC)

The MMWR series is often called "the voice of CDC." It is the agency's primary vehicle for scientific publication of timely, reliable, authoritative, accurate, objective, and useful public health information and recommendations. MMWR readership predominantly consists of physicians, nurses, public health practitioners, epidemiologists and other scientists, researchers, educators, and laboratorians. The data in the weekly MMWR are provisional, based on weekly reports to CDC by state health departments. The Surveillance Summaries provide a means for CDC programs to disseminate surveillance findings, permitting detailed interpretation of trends and patterns based on those findings. The MMWR series is available online at: http://www.cdc.gov/mmwr/publications/index.html. The CDC Surveillance Summaries are available online at: http://www.cdc.gov/mmwr/mmwr_ss/ss_cvol.html.

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The Excellence in Science Committee (EISC) at the Centers for Disease Control and Prevention (CDC)

The EISC promotes the CDC's scientific infrastructure and facilitates communication and collaboration that enhance scientific areas and activities needed for state-of-the-art conduct of science to foster, support, and protect an environment for the promotion of scientific integrity, quality assurance, and the rapid dissemination of scientific innovations, technology, and information with the ultimate goal of improving public health. More information about the EISC is available online at: http://www.cdc.gov/od/science/excellence/.

The Center for Disease Control and Prevention (CDC) Clearance Policies

The Office of the Associate Director for Science (OADS) (http://www.cdc.gov/od/science/) at the Center for Disease Control and Prevention (CDC) provides service and support to CDC scientists as they work to protect people's health and improve their quality of life. OADS' focus is on strengthening the quality and integrity of CDC's science and is home to the Office of Science Quality and the Office of Scientific Integrity. Furthermore, by fostering innovative and successful scientific collaborations and partnerships, OADS is also working towards enhancing the relevance of CDC's science and its health impact. OADS is also home to the Office of Science Quality (OSQ) (http://www.cdc.gov/od/science/quality/), which is responsible for advancing the quality of CDC's science and championing the translation of research through the development of science policies and best practices (e.g., authorship, scientific clearance, peer review, and extramural research policies); and the Office of Scientific Integrity (http://www.cdc.gov/od/science/integrity/), which ensures that CDC science and research activities comply with various federal laws, regulations, and policies; coordinates the agency's 301(d) and 308(d) confidentiality protections; ensures leadership in public health ethics; and provides trainings to promote a well-educated and ethical domestic and international workforce at CDC. Publication is encouraged and managed by editorial and clearance policies conducted at all levels of the Center.

Public Health Image Library

The Centers for Disease Control and Prevention (CDC) created the Public Health Image Library (PHIL), recognizing that much of the information critical to the communication of public health messages is pictorial rather than text-based. The PHIL offers an organized, universal electronic gateway to CDC's pictures. Public health professionals, the media, laboratory scientists, educators, students, and the worldwide public are welcome to use this material for reference, teaching, presentation, and public health messages. The content is organized into hierarchical categories of people, places, and science, and is presented as single images, image sets, and multimedia files. The PHIL is available online at: http://phil.cdc.gov/.

U.S. Food and Drug Administration (FDA) Publications

The FDA encourages its scientists to publish their findings in peer-reviewed science journals, books, and related articles. An actively updated and searchable research publications database for all FDA publications is available online at: http://www.accessdata.fda.gov/scripts/publications/.

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U.S. Food and Drug Administration (FDA) Office of Science and Engineering Laboratories (OSEL) Annual Report

The OSEL Annual Report provides current information about the Office's organization and intramural science activities; provides a summary of the Office's direct laboratory support for pre- market review and compliance cases; and provides a bibliography of scientific publications, presentations, and research seminars for the fiscal year. Annual reports are available online at: http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDRH/CDRH Reports/ucm109778.htm.

U.S. Food and Drug Administration (FDA) Center for Biologics Evaluation and Research (CBER) Website

This CBER website provides links to the strategic plan for regulatory science and research, general information about research programs, as well as highlights from selected research publications: http://www.fda.gov/BiologicsBloodVaccines/ScienceResearch/default.htm.

The National Institutes of Health (NIH) Public Access Policy

The NIH Public Access Policy ensures that the public has access to the published results of NIH funded research. It requires scientists to submit final peer-reviewed journal manuscripts that arise from NIH funds to the National Library of Medicine's digital archive PubMed Central (http://www.ncbi.nlm.nih.gov/pmc/) upon acceptance for publication. To help advance science and improve human health, the Policy requires that these papers are accessible to the public on PubMed Central no later than 12 months after publication. The NIH Public Access Policy is available online at: http://publicaccess.nih.gov/policy.htm.

The National Institutes of Health (NIH) Review Mechanism for Dual Use Research Manuscripts

The NIH has established a review mechanism for manuscripts which may involve dual use research of concern. The Publication and Abstract Clearance Form is available online at: http://www1.od.nih.gov/oir/sourcebook/oversight/pub-clear-form.htm. The Dual Use Questionnaire is available online at: http://sourcebook.od.nih.gov/oversight/Dual%20Use%20Questionnaire-4- 2010.pdf.

The National Institutes of Health (NIH) Instruction in the Responsible Conduct of Research

The NIH requires responsible conduct of research (RCR) instruction for all trainees, fellows, participants, and scholars receiving support through NIH training, career development award (individual or institutional), research education grant, and dissertation research grant. RCR is defined as the practice of scientific investigation with integrity. It involves the awareness and application of established professional norms and ethical principles in the performance of all activities related to scientific research. The NIH Policy is available online at: http://grants1.nih.gov/grants/guide/notice-files/NOT-OD-10-019.html. NIH materials for Research Conduct and Ethics Instruction, including case studies for the 2012 theme (Mentoring) are available online at: http://sourcebook.od.nih.gov/resethicscases/cases-toc.htm.

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Form E

BWC - Confidence Building Measure

Declaration of legislation, regulations and other measures

United States of America

April 15, 2013

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Form E

Declaration of legislation, regulations and other measures

Amended Since Last Legislation Regulations Other6 year

(a) Development, production, stockpiling, acquisition or retention of microbial or other biological agents, or YES YES YES NO toxins, weapons, equipment and means of delivery specified in Article I (b) Exports of Micro-Organisms7 and Toxins YES YES YES YES (c) Imports of Micro-Organisms and Toxins YES YES NO NO (d) Biosafety8 and biosecurity9 YES YES YES YES

(b) Exports of Micro-Organisms and Toxins Changes to Regulations

A regulation change was published in the July 2, 2012 Federal Register (77 FR 39353) to amend the Export Administration Regulations (EAR) by adding a note to clarify that items controlled under (Export Control Classification Number) ECCN 1A004 include Powered Air Purifying Respirators (PAPRA) that are designed or modified for defense against biological agents or other specified materials, among other changes. (http://www.bis.doc.gov/federal_register/rules/2012/77fr39353.pdf) A second regulation change was also published in the July 2, 2012 Federal Register (77 FR 39162) to amend the Export Administration Regulations by removing Bartonella quintana and Rickettsia rickettsii from the list of biological agents under (Export Control Classification Number) ECCN 1C351, revising a technical note to include certain de novo chemically synthesized genetic material and artificially-produced organisms under ECCN 1C353, removing the redundant phrase, “without propagation of aerosols,” from the descriptors for cross (tangential) flow filtration equipment under ECCN 2B352, and providing alternative, but equal, descriptors on steam sterilizable freeze-drying (lyophilization) equipment also under 2B352, among other changes. (http://www.bis.doc.gov/federal_register/rules/2012/77fr39162.pdf)

(d) Biosafety and biosecurity Changes to Regulations

Possession, Use, and Transfer of Select Agents and Toxins; Biennial Review The Bioterrorism Preparedness Act requires that the HHS Secretary review and republish the list of select agents and toxins on at least a biennial basis. The rules were also written in response to Executive

6 Including guidelines. 7 Micro-organisms pathogenic to man, animals and plants in accordance with the Convention. 8 In accordance with the latest version of the WHO Laboratory Biosafety Manual or equivalent national or international guidance. 9 In accordance with the latest version of the WHO Laboratory Biosecurity Guidance or equivalent national or international guidance. Page 209 of 237

Order 13546, "Optimizing the Security of Biological Select Agents and Toxins in the United States," which directed the HHS and U.S. Department of Agriculture (USDA) Secretaries to (1) designate a subset of the select agents and toxins list (Tier 1) that presents the greatest risk of deliberate misuse with the most significant potential for mass casualties or devastating effects to the economy, critical infrastructure, or public confidence; (2) explore options for graded protection for these Tier 1 agents and toxins to permit tailored risk management practices based upon relevant contextual factors; and (3) consider reducing the overall number of agents and toxins on the select agents and toxins list. The rules (HHS and USDA) add three new agents and remove twenty-three agents and toxins. The additions and deletions were part of the biennial review required by law and based on study of the existing list of select agents and toxins. The rules will continue the federal government's now 10-year commitment to ensuring the proper oversight of the transfer, storage, and use of select agents and toxins by laboratories throughout the country doing important research to protect the lives of all Americans. (Final Action October 2012) Direct Final Rule and Companion Notice of Proposed Rulemaking: Control of Communicable Diseases: Interstate In this Direct Final Rule, the Centers for Disease Control and Prevention (CDC), located within the Department of Health and Human Services (HHS) is proposing to update the definitions for interstate quarantine regulations to reflect modern terminology and plain language used by private industry and public health partners. These updates will not affect current practices. As part of the update, we are updating two existing definitions and adding eight new definitions to clarify existing provisions, as well as updating regulations to reflect the most recent Executive Order addressing quarantinable communicable diseases. (https://www.federalregister.gov/articles/2012/12/26/2012-30729/control-of- communicable-diseases-interstate-scope-and-definitions) (Final Action -December 2012) Direct Final Rule Stage: Control of Communicable Diseases: Foreign and Possessions This direct final rule and companion notice of proposed rulemaking updates definitions to reflect modern terminology and plain language used globally by industry and public health partners. As part of the update, we are updating five existing definitions; adding thirteen new definitions to help clarify existing provisions; creating a new scope and definitions section for Importations under a new section by reorganizing existing definitions into this new section; and updating regulations to reflect the language used by the most recent Executive Order regarding quarantinable communicable diseases. (https://www.federalregister.gov/articles/2012/12/26/2012-30723/control-of-communicable-diseases- foreign-scope-and-definitions) (Final Action - December 2012)

(d) Biosafety and biosecurity Other measures

Changes to Security of Select Agents and Toxins (HHS, USDA, and DOJ) In accordance with Executive Order 13546 (Optimizing the Security of Biological Select Agents and Toxins in the United States) signed by the President on July 2, 2010, the Federal Select Agent Program convened an Interagency Working Group to execute sections 6(a) and 8 of the Executive Order. This working group, which includes representatives from the Departments of Justice (DOJ), Energy (DOE), Homeland Security (DHS), Defense (DOD), and the Environmental Protection Agency (EPA), has developed procedures and policies to better coordinate the inspections of entities that are federally owned or federally funded; improve information sharing between Departments and Agencies, and implement other activities so that effective oversight can be achieved with a minimal disruption of critical biodefense functions.  Joint inspections: A joint inspection program has been initiated between the Federal Select Agent Program and other federal agencies that fund or own entities where select agent/toxin work is conducted to minimize the number of select agent inspections that these entities undergo per year. Since the initiation of the joint inspection program, the Federal Select Agent Program has participated in 24 joint inspections.

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 Information sharing: Memoranda of understanding have been signed between the Federal Select Agent Program and DHS, DOD, EPA, DOE, and Veterans Health Administration to share information including inspection data.  Inspector Training Program: The Federal Select Agent Program has trained 5 individuals from DHS and 4 individuals from DOD. The goal of the program is to provide the knowledge, skills and experience to federal partners to enable them to conduct "internal" inspections of registered entities they own or fund, or to conduct joint inspections with the Federal Select Agent Program. Select Agent Program Guidance The Federal Select Agent Program issues guidance to the regulated community to assist entities with complying with the requirements of the select agent regulations. Guidance issued in 2012 included:  Containment Facility Design and Construction (Secondary Barriers)  Containment for Work with Eastern Equine Encephalitis virus  Guidance for Meeting Training Requirements of the Select Agent Regulations  Guidance for Suitability Assessments  Guidance for the Inactivation of Select Agents and Toxins  Guidance on the Shipment and Receipt of Packages with Select Agents and Toxins  Guidance on the Use of Infectious Waste Treatment and Radiation Facilities Outside of Registered Space  Guidelines for Avian Influenza Viruses  Incident Response Plan  Information Systems Security Control Guidance Document  Long Term Storage  Occupational Health Program Guidance Document for Working with Tier 1 Select Agents and Toxins  Prudent Practices in the Laboratory: Handling and Management of Chemical Hazards  Responsible Official Guidance Document  “SA Grams” (communication documents to the registered entities)  Security Guidance for Select Agent or Toxin Facilities  Security Risk Assessment Tool  Synthetic Genomics  Toxin Due Diligence Provision A complete list of all of the guidance issued to date is available at the Federal Select Agent Program website: http://www.selectagents.gov/. Updates to the Federal Experts Security Advisory Panel Recommendations Concerning the Select Agent Program The Federal Experts Security Advisory Panel (FESAP) was created in July 2010 by Executive Order (EO) 13546, "Optimizing the Security of Biological Select Agents and Toxins in the United States," and tasked to make recommendations regarding the biosecurity measures of the national Select Agent Program (SAP). In March 2012, the FESAP provided recommendations to the SAP on personnel reliability measures relevant to the Program. These recommendations were taken into consideration and incorporated, as appropriate, in the Guidance Document entitled, "Guidance for Suitability Assessments," which is available online at http://www.selectagents.gov/Guidance_Documents.html along with other Guidance documents. Considerations for the Development and Dissemination of Codes of Conduct for Dual Use Research In addition to its standing charge to advise on strategies and tools to promote awareness of the dual use issue in the life sciences community generally, the U.S. Government charged the National Science Advisory Board for Biosecurity (NSABB) with advising on the development, utilization and promotion of codes of conduct for dual use research to interdisciplinary life scientists, and relevant professional groups. The Board's recommendations address strategies to develop a code of conduct, the importance of strong

Page 211 of 237 institutional support for such endeavor, considerations for the dissemination of a code of conduct, and the need to assess the effectiveness of a code of conduct overtime. The report also provides two tools for developing a code of conduct: a toolkit that includes concrete steps in developing and disseminating a code of conduct for dual use research and an educational module on dual use research that may be used either alone or in conjunction with the toolkit. The NSABB report can be found online at: http://oba.od.nih.gov/oba/biosecurity/documents/COMBINED_Codes_PDFs.pdf. The code of conduct toolkit can be found online at: http://oba.od.nih.gov/oba/biosecurity/documents/A_code_of_conduct_tool_kit_PPJan2012.pdf. The dual use research of concern education module can be found online at: http://oba.od.nih.gov/oba/biosecurity/documents/A_code_of_conduct_tool_kit_PPJan2012.pdf. United States Government Policy for Oversight of Life Sciences Dual Use Research of Concern On March 29, 2012, the United States Government (USG) published a policy for review of USG- funded or conducted research with certain high-consequence pathogens and toxins for its potential to be dual use research of concern (DURC) in order to: (a) mitigate risks where appropriate; and (b) collect information needed to inform the development of an updated policy, as needed, for the oversight of DURC. The fundamental aim of this oversight is to preserve the benefits of life sciences research while minimizing the risk of misuse of the knowledge, information, products, or technologies provided by such research. (http://oba.od.nih.gov/oba/biosecurity/PDF/United_States_Government_Policy_for_Oversight_of_DURC _FINAL_version_032812.pdf) FBI Biosecurity Outreach  During 2012, the FBI conducted 24 academic biosecurity outreach events to research institutions across the United States and two FBI sponsored national-level outreach events were conducted, the first focused on mitigating the potential for misuse of life sciences research (i.e., dual use research) and the second focused on developing strategies to improve biosecurity as research continues to be globalized. The FBI also co-sponsored a meeting to determine the feasibility of harmonizing commercial DNA orders between U.S. and European consortia, allowing for coordination and collaboration to prevent potential misuse of genetic material.  During 2012, the FBI conducted one biosecurity outreach event with amateur biology communities from the United States, Europe, and Southeast Asia. Over the past decade, amateur biology communities have undergone rapid growth. The FBI has developed partnerships with the amateur biology community in order to garner their assistance in preventing, detecting, and responding to incidents of possible misuse. FBI/CDC Joint Criminal and Epidemiological Investigation Training  During 2012, the FBI conducted six Joint Criminal and Epidemiological Investigations training courses across the United States. Through this effort, law enforcement and public health gain mutual familiarity with criminal and epidemiological investigations and learn how each can support the other through the sharing of information, expertise and resources.

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Form F

BWC - Confidence Building Measure

Declaration of Past Activities in Offensive and/or Defensive Biological Research and Development Programmes

United States of America

April 15, 2013

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Form F

Declaration of Past Activities in Offensive and/or Defensive Biological Research and Development Programmes

1. Date of entry into force of the Convention for the State party.

26 March 1975

2. Past offensive biological research and development programmes:

Nothing new to declare

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Form G

BWC - Confidence Building Measure

Declaration of Vaccine Production Facilities

United States of America

April 15, 2013

Page 215 of 237

Form G

Declaration of vaccine production facilities

The U.S. Food and Drug Administration publishes a current list of vaccines licensed in the United States, including associated production facilities. This list is available at: http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm093833.htm.

Data provided on CBM Form G are excerpted from the publicly available website listed above (as accessed on 25 February 2012). Trade names are included when provided by the manufacturer. Specific and current information about a vaccine, and contact information for the manufacturer, are available by following the hyperlinks provided on the above website.

Page 216 of 237

Form G

Declaration of vaccine production facilities

1. Name of facility

Barr Laboratories, Inc. 2. Location (Mailing Address)

2150 Perrowville Road Forest, Virginia 24551

3. General description of the types of diseases covered:

Adenovirus Type 4 and Type 7 Vaccine, Live, Oral

Vaccines: • Adenovirus Type 4 and Type 7 Vaccine, Live, Oral

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Form G

Declaration of vaccine production facilities

1. Name of facility

Emergent BioDefense Operations Lansing, Inc. 2. Location (Mailing Address)

3500 N. Martin Luther King Jr. Blvd. Lansing, Michigan 48906

3. General description of the types of diseases covered:

Anthrax disease caused by Bacillus anthracis

Vaccines: • Anthrax Vaccine Adsorbed - [BioThrax]

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Form G

Declaration of vaccine production facilities

1. Name of facility

MassBiologics 2. Location (Mailing Address)

University of Massachusetts Medical School Boston, Massachusetts 02130

3. General description of the types of diseases covered:

Diphtheria and tetanus caused by Corynebacterium diphtheriae and Clostridium tetani.

Vaccines: • Tetanus and Diphtheria Toxoids Adsorbed

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Form G

Declaration of vaccine production facilities

1. Name of facility

MedImmune LLC 2. Location (Mailing Address)

One MedImmune Way Gaithersburg, Maryland 20878

3. General description of the types of diseases covered:

Influenza disease caused by influenza virus subtypes A and B.

Vaccines: • Influenza Vaccine Live, Intranasal - [FluMist] • Influenza Vaccine Live, Intranasal (FluMist® Quadravalent)

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Form G

Declaration of vaccine production facilities

1. Name of facility

Merck Sharp & Dohme Corp. 2. Location (Mailing Address)

PO Box 1000, UG2D-68 West Point, Pennsylvania 19486-0004

3. General description of the types of diseases covered:

Invasive disease caused by Haemophilus influenzae type b; infection caused by all known subtypes of hepatitis B virus; Hepatitis A disease; cervical, vulvar and vaginal cancer and certain other diseases caused by Human Papillomavirus (HPV) Types 6, 11, 16, and 18; Measles (rubeola); Mumps; diseases caused by Streptococcus pneumoniae; Rotavirus disease; Rubella (German measles) disease; Varicella disease caused by the varicella-zoster virus (VZV); Herpes zoster (shingles) disease.

Vaccines: • Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate) - [PedvaxHIB] • Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate) & Hepatitis B (Recombinant) Vaccine - [COMVAX] • Hepatitis A Vaccine, Inactivated - [VAQTA] • Hepatitis B Vaccine (Recombinant) - [Recombivax HB] • Human Papillomavirus Quadrivalent (Types 6, 11, 16, 18) Vaccine, Recombinant - [Gardasil] • Measles Virus Vaccine Live (ATTENUVAX®) • Measles, Mumps, and Rubella Virus Vaccine, Live - [M-M-R II] • Measles, Mumps, Rubella and Varicella Virus Vaccine Live - [ProQuad] • Mumps Virus Vaccine Live, Jeryl Lynn Strain (Mumpsvax®) [no longer being made] • Pneumococcal Vaccine, Polyvalent - [Pneumovax 23] • Rotavirus Vaccine, Live, Oral, Pentavalent - [RotaTeq] • Rubella Virus Vaccine Live (MERUVAX® II) • Varicella Virus Vaccine Live - [Varivax] • Zoster Vaccine, Live, (Oka/Merck) - [Zostavax]

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Form G

Declaration of vaccine production facilities

1. Name of facility

Organon Teknika Corporation LLC 2. Location (Mailing Address)

100 Rodolphe Street Building 1300 Durham, North Carolina 27712

3. General description of the types of diseases covered:

For the prevention of tuberculosis

Vaccines: • BCG Live (BCG Vaccine)

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Form G

Declaration of vaccine production facilities

1. Name of facility

Protein Sciences Corporation 2. Location (Mailing Address)

1000 Research Parkway Meriden, Connecticut 06450-7159

3. General description of the types of diseases covered:

For active immunization against disease caused by influenza virus subtypes A and B

Vaccines: • Influenza vaccine for subtypes A and B, (Flublock®)

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Form G

Declaration of vaccine production facilities

1. Name of facility

Sanofi Pasteur Biologics Co. 2. Location (Mailing Address)

38 Sidney Street Cambridge, Massachusetts 02139

3. General description of the types of diseases covered:

Smallpox disease

Vaccines: • Smallpox (Vaccinia) Vaccine, Live - [ACAM2000]

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Form G

Declaration of vaccine production facilities

1. Name of facility

Sanofi Pasteur, Inc 2. Location (Mailing Address)

Discovery Drive Swiftwater, Pennsylvania 18370

3. General description of the types of diseases covered:

Diphtheria caused by Corynebacterium diphtheria; tetanus caused by Clostridium tetani; pertussis (whooping cough) caused by Bordetella pertussis; influenza disease caused by pandemic (H1N1) 2009 virus; influenza disease caused by H5N1 subtype; influenza disease caused by influenza virus subtypes A and B; invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135; meningitis and meningococcemia caused by N. meningitidis; and Yellow fever acute viral illness caused by a mosquito-borne flavivirus.

Vaccines: • Diphtheria & Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed - [Tripedia; DTaP] • Diphtheria and Tetanus Toxoids Adsorbed USP (For Pediatric Use) (DT) • Influenza Virus Vaccine (Fluzone®, Fluzone High-Dose and Fluzone Intradermal) • Influenza Virus Vaccine, H5N1 • Meningococcal Polysaccharide (Serogroups A, C, Y and W-135) Diphtheria Toxoid Conjugate Vaccine - [Menactra®] • Meningococcal Polysaccharide Vaccine, Groups A, C, Y and W-135 Combined - [Menomune®-A/C/Y/W-1351] • Tetanus and Diphtheria Toxoids Adsorbed for Adult Use - [DECAVAC] • Tetanus Toxoid Adsorbed • Tetanus Toxoid for Booster Use Only • Yellow Fever Vaccine - [YF-VAX®]

Page 225 of 237

Form G

Declaration of vaccine production facilities

1. Name of facility

Wyeth Pharmaceuticals Inc 2. Location (Mailing Address)

Pfizer, Inc., 235 East 42nd Street New York, New York 10017

3. General description of the types of diseases covered:

Invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F and otitis media caused by Streptococcus pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F and 23F.

Vaccines: • Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein) - [Prevnar 13]

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Appendix A

Biological Select Agents and Toxins

Biological Select Agents and Toxins are biological pathogens and toxins that the United States has determined have the potential to pose a severe threat to public health and safety, animal and plant health, or animal and plant products. The possession, use, and transfer of these agents is regulated by the U.S. Department of Health and Human Services (HHS) Centers for Disease Control and Prevention and the U.S. Department of Agriculture Animal and Plant Health Inspection Service under the Select Agent Regulations found in Part 73 of Title 42 of the Code of Federal Regulations, Part 331 of Title 7 of the Code of Federal Regulations, and Part 121 of Title 9 of the Code of Federal Regulations.

Information on Biological Select Agents and Toxins can be found on the National Select Agent Registry website: http://www.selectagents.gov.

HHS Select Agents and Toxins Abrin Rickettsia rickettsii Botulinum neurotoxins Saxitoxin Botulinum neurotoxin-producing species of Shiga-like ribosome inactivating proteins Clostridium Shigatoxin Cercopithecine herpesvirus 1 (Herpes B virus) South American Haemorrhagic Fever viruses Clostridium perfringens epsilon toxin • Flexal • Machupo • Guanarito • Sabia • Junin Coccidioides posadasii/Coccidioides immitis Staphylococcal enterotoxins Conotoxins T-2 toxin Coxiella burnetii Tetrodotoxin Crimean-Congo haemorrhagic fever virus Tick-borne encephalitis complex (flavi) viruses Diacetoxyscirpenol • Central European Tick-borne encephalitis Eastern Equine Encephalitis virus • Far Eastern Tick-borne encephalitis Ebola virus • Kyasanur Forest disease • Omsk Hemorrhagic Fever Francisella tularensis • Russian Spring and Summer encephalitis Lassa fever virus Variola major virus (Smallpox virus) Marburg virus Variola minor virus (Alastrim) Monkeypox virus Yersinia pestis Reconstructed replication competent forms of the 1918 pandemic influenza virus containing any portion of the coding regions of all eight gene segments (Reconstructed1918 Influenza virus) Ricin Rickettsia prowazekii

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OVERLAP Select Agents and Toxins Bacillus anthracis Burkholderia pseudomallei (formerly Brucella abortus Pseudomonas pseudomallei) Brucella melitensis Hendra virus Brucella suis Nipah virus Burkholderia mallei (formerly Pseudomonas Rift Valley fever virus mallei) Venezuelan Equine Encephalitis virus

USDA Select Agents and Toxins African horse sickness virus Menangle virus African swine fever virus Mycoplasma capricolum subspecies Akabane virus capripneumoniae (contagious caprine Avian influenza virus (highly pathogenic) pleuropneumonia) Bluetongue virus (exotic) Mycoplasma mycoides subspecies mycoides small colony (Mmm SC) (contagious bovine Bovine spongiform encephalopathy agent pleuropneumonia) Camel pox virus Peste des petits ruminants virus Classical swine fever virus Rinderpest virus Ehrlichia ruminantium (Heartwater) Sheep pox virus Foot-and-mouth disease virus Swine vesicular disease virus Goat pox virus Vesicular stomatitis virus (exotic): Indiana Japanese encephalitis virus subtypes VSV-IN2, VSV-IN3 Lumpy skin disease virus Virulent Newcastle disease virus 1

Malignant catarrhal fever virus (Alcelaphine herpesvirus type 1)

USDA PLANT PROTECTION AND QUARANTINE (PPQ) Select Agents and Toxins Peronosclerospora philippinensis Sclerophthora rayssiae var zeae (Peronosclerospora sacchari) Synchytrium endobioticum Phoma glycinicola (formerly Pyrenochaeta Xanthomonas oryzae glycines) Xylella fastidiosa (citrus variegated chlorosis Ralstonia solanacearum race 3, biovar 2 strain) Rathayibacter toxicus

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Appendix A

NIAID Category A, B, and C Priority Pathogens The National Institute of Allergy and Infectious Disease (NIAID) categorization of pathogens identifies specific pathogens as priorities for additional research efforts as part of the NIAID biodefense research agenda.

Additional information on NIAID Category A, B, and C Priority Pathogens is available at: http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/research/Pages/CatA.aspx http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/Documents/categorybandc.pdf

Category A pathogens are those organisms/biological agents that pose the highest risk to national security and public health because they  Can be easily disseminated or transmitted from person to person  Result in high mortality rates and have the potential for major public health impact  Might cause public panic and social disruption  Require special action for public health preparedness

Category A Priority Pathogens Bacillus anthracis (anthrax) Clostridium botulinum toxin (botulism) Yersinia pestis (plague) Variola major (smallpox) and other related pox viruses Francisella tularensis (tularemia) Viral hemorrhagic fevers Arenaviruses (LCMV, Junin virus, Machupo virus, Guanarito virus, Lassa virus) Bunyaviruses (Hantaviruses, Rift Valley Fever virus) Flaviruses (Dengue virus) Filoviruses (Ebola, Marburg viruses)

Category B pathogens are the second highest priority organisms/biological agents. They  Are moderately easy to disseminate  Result in moderate morbidity rates and low mortality rates  Require specific enhancements for diagnostic capacity and enhanced disease surveillance

Category B Priority Pathogens Burkholderia pseudomallei Coxiella burnetii (Q fever) Brucella species (brucellosis) Burkholderia mallei (glanders) Chlamydia psittaci (Psittacosis) Ricin toxin (from Ricinus communis) Epsilon toxin of Clostridium perfringens Staphylococcus enterotoxin B Typhus fever (Rickettsia prowazekii) Food- and Waterborne Pathogens  Bacteria: Diarrheagenic E.coli, Pathogenic Vibrio, Shigella species, Salmonella, Listeria monocytogenes, Campylobacter jejuni, Yersinia enterocolitica  Viruses: Caliciviruses, Hepatitis A virus

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 Protozoa: Cryptosporidium parvum, Cyclospora cayatanensis, Giardia lamblia, Entamoeba histolytica, Toxoplasma  Fungi: Microsporidia Additional viral encephalitides: West Nile Virus, LaCrosse virus, California encephalitis virus, Venezuelan equine encephalitis virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Japanese Encephalitis Virus, Kyasanur Forest Virus

Category C pathogens are the third highest priority and include emerging pathogens that could be engineered for mass dissemination in the future because of  Availability  Ease of production and dissemination  Potential for high morbidity and mortality rates and major health impact

Category C Priority Pathogens Emerging infectious disease threats such as Nipah virus and additional hantaviruses Tickborne hemorrhagic fever viruses (Crimean-Congo Hemorrhagic fever virus) Tickborne encephalitis viruses Yellow fever Tuberculosis, including drug-resistant TB Influenza Other Rickettsias Rabies Prions Chikungunya virus Severe acute respiratory syndrome associated coronavirus (SARS-CoV) Coccidioides immitis Coccidioides posadasii Antimicrobial resistance, excluding research on sexually transmitted organisms10  Research on mechanisms of antimicrobial resistance  Studies of the emergence and/or spread of antimicrobial resistance genes within pathogen populations  Studies of the emergence and/or spread of antimicrobial-resistant pathogens in human populations  Research on therapeutic approaches that target resistance mechanisms  Modification of existing antimicrobials to overcome emergent resistance Antimicrobial research, as related to engineered threats and naturally occurring drug-resistant pathogens, focused on development of broad-spectrum antimicrobials Innate immunity, defined as the study of nonadaptive immune mechanisms that recognize, and respond to, microorganisms, microbial products, and antigens

10 NIAID Category C Antimicrobial Resistance—Sexually Transmitted Excluded Organisms: Bacterial vaginosis, Chlamydia trachomatis, Cytomegalovirus, Granuloma inguinale, Hemophilus ducreyi, Hepatitis B virus, Hepatitis C virus, Herpes Simplex virus, Human immunodeficiency virus, Human papillomavirus, Neisseria gonorrhea, Treponema pallidum, Trichomonas vaginalis Page 230 of 237

Appendix B

Compiled list of biological agents and toxins used for biodefense research

Biological Agents

African swine fever virus

A Alcaligenes faecalis Acanthamoeba castellanii Alternaria spp. Acetivibrio ethanolgignens Anaerobiospirillum Achromobacter xylosidans Anaeroplasma Achromobacter xylosoxidans Andes virus Acidithiobacillus spp. Aneurinibacillus migulanus Acinetobacter baumannii Aspergillus flavus Acinetobacter lwoffii Acinetobacter radioresistens Aspergillus niger Actinobacillus equuli Aspergillus versicolor Actinobacillus lignieresii Avian influenza virus Actinobacillus pleuropneumoniae Avian influenza virus, highly pathogenic Actinomyces naeslundii Avian influenza virus, highly pathogenic Adenovirus (recombinant vaccine reference strains of H5N1 Adenovirus type 5 and H5N3 subtypes) Aerococcus viridans Avian influenza virus, low pathogenicity Aeromonas hydrophila Avian metapneumonvirus Bovine adenovirus

B Bovine calicivirus Brachyspira alvinipulli Bovine herpesvirus Brachyspira hyodysenteriae Bovine herpes and retroviruses (untyped) Brachyspira innocens Bovine immunodeficiency virus Brachyspira pilosicoli Bovine lentivirus Bacillus amyloliquefaciens Bovine papular stomatitis virus Bacillus anthracis Bovine parainfluenza virus Bacillus anthracis Delta Stern Bovine parvovirus Bacillus atrophaeus Bovine respiratory syncytial virus Bacillus benzoevorans Bovine spongiform encephalopathy agent Bacillus brevis Bacillus cereus Bovine spumavirus Bacillus circulans Bovine viral diarrhea virus Bacillus coagulans Brevibacillus parabrevis Bacillus firmus Brucella abortus Bacille Calmette-Guérin Brucella canis Bacillus globigii Brucella ceti Brucella melitensis Bacillus globigii [atrophaeus] spores Bacillus licheniformis Brucella neotomae Bacillus macerans Brucella ovis Bacillus megaterium Brucella pinnipedialis Bacillus mycoides Brucella suis Bacillus polymyxa Brugia malayi Bacillus psychrosaccharolyticus Burkholderia andropogonis Bacillus pumilus Burkholderia caryophylli Bacillus samanii Burkholderia cenocepacia Bacillus sphaericus Burkholderia cepacia

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Bacillus stearothermophilus Burkholderia gladioli Bacillus subtilis Burkholderia glumae Bacillus subtilis FD6404 Bluetongue virus Bacillus subtilis variant niger Border disease virus Bacillus thailandensis Bordetella avium Bacillus thuringiensis Bordetella bronchiseptica Bacillus thuringiensis Al Hakam Bordetella hinzii Bacillus thuringiensis israelensis Bordetella pertussis Bacillus thuringiensis kurstaki Borrelia burgdorferi Bacteriophage Burkholderia mallei Bacteriophage MS2 Burkholderia multivorans Bacteroides fragilis Burkholderia pseudomallei Bacteroides uniformis Burkholderia pyrrocinia Bartonella henselae Burkholderia stabilis Bifidobacterium dentium Burkholderia thailandensis Bifidobacterium longum Burkholderia ubonensis Black Creek Canal virus Burkholderia vietnamensis Citrobacter species

C Classical swine fever virus California encephalitis virus Cladosporium cladosporioides Camel pox virus Clavibacter michiganense Campylobacter coli Clostridium argentinense Campylobacter fetus Clostridium botulinum Campylobacter jejuni Clostridium botulinum, botulinum neurotoxin Campylobacter lari producing species Campylobacter sputorum Clostridium butyricum Candida albicans Clostridium clostridioforme Candida glabrata Clostridium difficile Canine calicivirus Clostridium hathewayi Canine coronavirus Clostridium innocuum Canine Distemper virus Clostridium novyi Canine parvovirus Clostridium orbiscindens Caprine adenovirus Clostridium perfringens Caprine herpesvirus Clostridium septicum Caprine lentivirus Clostridium sordelli Caprine respiratory syncytial virus Clostridium sporogenes Caulobacter vibrioides Clostridium symbiosum Cedecea neteri Clostridium tetani Central European Tick-borne encephalitis virus Coccidiodes immitis Cercopithecine herpesvirus Coronavirus Chaetomium globosum Corynebacterium amycolatum Chapare virus Corynebacterium bovis Chikungunya virus Corynebacterium minutissimum Chlamydia pneumoniae Corynebacterium pseudotuberculosis Chlamydia psittaci Cowpox virus Chlorella pyrenoidosa Coxiella burnetii Chlorella sorokiniana Coxsackievirus Chromobacterium violaceum Crimean-Congo hemorrhagic fever virus Chronic wasting disease Cyanobacteria spp. Chryseobacterium indologenes Cytomegalovirus Chryseobacterium spp. Cytophaga marinoflava Citrobacter freundii

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Dengue virus D Dengue/Langat chimera Deinococcus grandis Dengue/TBEV chimera Deinococcus radiodurans Dobrava virus Delftia acidovorans Epizootic hemorrhagic disease virus

E Equine adenovirus Eastern equine encephalitis virus Equine arteritis virus Ebola virus Equine herpesvirus Encephalomyocarditis virus Erwinia herbicola Enteric viruses of poultry Erysipelothrix spp. Enterobacter aerogenes Escherichia coli BL21 Enterobacter cloacae Enterobacter hormaechei Escherichia coli HB101 Enterococcus casseliflavus Escherichia coli K12 Enterococcus durans Escherichia coli 0157:H7 Enterococcus faecalis Escherichia coli 0157:H7 (killed) Francisella novicida-like isolates

F Francisella novicida Utah 112 Far-Eastern tick-borne encephalitis virus Francisella philomiragia Feline calicivirus Francisella tularensis Feline infectious peritonitis virus Francisella tularensis holartica Feline parvovirus Francisella tularensis LVS strain Flavobacterium mizutaii Francisella tularensis Schu4 (CRP inactivated) Flexal virus Fusarium oxysporum Foot and Mouth Disease virus Fusobacterium Fort Morgan virus Fusobacterium necrophorum Francisella novicida Geobacillus stearothermophilus G Goat pox virus Gemella morbillorum Granulicatella species Geobacillus caldoxylosilyticus Guanarito virus Hanta virus H Hantaan virus Haemophilus avium Helicobacter pylori Haemophilus influenza Hemophilus influenzae Haemophilus paragallinarium Hemorrhagic enteritis virus Haemophilus parainfluenzae Hendra virus Haemophilus parasuis Herbaspirillum seropedicae Haemophilus somnus Herpes simplex virus Hafnia alvei Human immunodeficiency virus Halanaerobium kushneri Human norovirus Halobacterium solanarium Hyphomicrobium vulgare Halomonas halmophilas Influenza virus (reconstructed 1918 ) -

I Reconstructed replication competent forms of the Infectious bursal disease virus 1918 flu pandemic containing any portion of the Influenza virus A coding regions of all eight gene segments Influenza virus B Junin virus J Junin virus vaccine strain Candid 1 Japanese Encephalitis virus Kluyvera ascorbata

K Kocuria kristinae Page 233 of 237

Klebsiella oxytoca Kunjin virus Klebsiella pneumoniae Kyasanur Forest disease virus Leptospira inadai

L Leptospira interrogans La Crosse virus Leptospira kirschneri Lactobacillus casei Leptospira noguchii Lactobacillus delbrueckerii Leptospira santarosai Lactobacillus gasseri Lactobacillus plantarum Leptospira weilii Lactococcus garvieae Leuconostoc mesenteroides Laguna Negra virus Leuconostoc pseudomesenteroides Lampropedia hyalina Liberabacter africanus Langat virus Liberabacter americanus Langat/TBEV chimera Liberabacter asiaticus Lassa virus Listeria monocytogenes Latino virus Listeria monocytogenes LVS Legionella pneumophila Lujo viros Leishmania amazonensis Lymphocytic Choriomeningitis virus Leptospira biflexa Lysinibacillus sphaericus Leptospira borgpetersenii Murid herpes virus

M Murine hepatitis virus Machupo virus Mycobacterium avium Magnaporthe grisea Mycobacterium bovis Mannheimia glucosida Mycobacterium bovis BCG Mannheimia haemolytica Mycobacterium kansasii Marburg virus Mycobacterium paratuberculosis Marek's disease herpesvirus Mycobacterium tuberculosis Menangle virus Mycobacterium tuberculosis (drug resistant) Micrococcus luteus Mycoplasma arginini Micrococcus spp. Mycoplasma capricolum Mink calicivirus Mogibacterium vescum Mycoplasma conjunctivae Monkey pox virus Mycoplasma gallisepticum Moose adenovirus Mycoplasma ovipnuemoniae Moraxella bovis Mycoplasma putrefaciens Moraxella catarrhalis Mycoplasma synoviae Neisseria lactamica N Neisseria mucosa Naegleria fowleri Newcastle disease virus Nannochloropsis spp. Nipah virus Neisseria flavescens Nitrosospira multiformis Neisseria gonorrhoeae Orf virus

O Ornithobacterium rhinotracheale Oceanospirillum maris Ovine adenovirus Ochromobactrum anthropi Ovine lentiviruses Odocoileus adenovirus Ovine parainfluenza virus Omsk Hemorrhagic fevervirus Ovine respiratory syncytial virus O'Nyong Nyong virus Oxalobacter formigenes

Plasmodium falciparum D6

P Plesiomonas shigelloides

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Paenibacillus macerans Plum Pox Virus Paenibacillus napthalenovorans Porcine adenovirus Pantoea agglomerans Porcine calicivirus Paracoccus denitrificans Porcine circovirus Parainfluenza virus Porcine enterovirus Pasteurella canis Porcine hemagglutinating encephalomyelitis virus Pasteurella dagmatis Porcine parvovirus Pasteurella gallinarum Porcine reovirus Pasteurella haemolytica Porcine reproductive and respiratory syndrome Pasteurella langae virus Pasteurella multocida Porcine respiratory coronavirus Pasteurella pnuemotropica Porphyrobacter sanguineus Pasteurella stomatis Powassan virus Pasteurella trehalosi Prevotella nigrescens Pasteurella ureae Prions Penicillium chryogenum Propionibacterium avidum Penicillium funinculosum Prospect Hill virus Peronosclerospora phillipinensis Proteus mirabilis Peronosclerospora sacchari Proteus vulgaris Phakopsora pachyrhizi Providencia stuartii Phanerochaete chrysosporium Pseudocowpox virus Phoma glycinicola (formerly Peronosclerospora Pseudomonas aeruginosa sacchari) Pseudomonas fluorescens Photobacterium damsela Pseudomonas oxalacticus Phytophthora infestans Psittacine herpesvirus Phytophthora kernoviae Puccinia graminis tritici Phytophthora ramorum Puccinia striiformis Pichinde virus Puumala virus Porcine astrovirus Rickettsia felis

R Rickettsia montanensis Rabbit pox virus Rickettsia prowazekii Ralstonia solanacearum Rickettsia rhipicephali Rathayibacter toxicus Rickettsia rickettsii Respiratory syncytial virus Rickettsia typhi Rhinovirus Riemerella anatipestifer Rhizobium leguminosarum Rift Valley Fever virus Rhizobium (Agrobacterium) radiobacter Rift Valley fever virus MP-12 Rhodobacter sphaeroides Rio Bravo virus Rhodococcus equi Ross River virus Rhodococcus erythropolis Russian Spring and Summer encephalitis virus Rickettsia conorii Simonsiella muelleri

S Sindbis virus Sabia virus Sin Nombre virus St. Louis encephalitis virus Soybean Dwarf virus Saccharomyces cerevisiae Sphingobacterium multivorum Salmonella bongori Sphingomonas paucimobilis Salmonella enterica Spiroplasma insolitum Salmonella enteritidis Squirrel fibroma virus Salmonella typhi Staphylococcus arlettae Salmonella typhimurium Staphylococcus aureus

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SARS coronavirus Staphylococcus capitis Semliki Forest virus Staphylococcus caprae Sendai virus Staphylococcus carnosus Seoul virus Staphylococcus intermedius Serratia marcescens Staphylococcus kloosii Sheep pox virus Staphylococcus lentus Shewanella colwelliana Staphylococcus saprophyticus Shewanella oneidensis Staphylococcus sciuri Shigella boydii Staphylococcus simulans Shigella dysenteriae Staphylococcus vitulinus Shigella flexneri Staphylococcus warneri Shigella sonnei Staphylococcus xylosus Simian hemorrhagic fever virus Stenotrophomonas maltophilia Simian Virus 40 Streptococcus agalactiae Staphylococcus chromogenes Streptococcus cricetus Staphylococcus cohnii Streptococcus equinus Staphylococcus epidermidis Streptococcus haemolyticus Staphylococcus equorum Streptococcus pneumoniae Staphylococcus gallinarum Streptococcus pyogenes Staphylococcus haemolyticus Streptomyces coelicolor Staphylococcus hominis Streptomyces lividans Swine influenza virus Thermus aquaticus T Tick-borne encephalitis virus Tacaribe virus Toxoplasma gondii Tatlockia maceachernii Treponema pallidum Thermomonospora chromogena Trypanosoma cruzi Thermomyces lanuginosus Vibrio cholerae 0:139 V Vibrio corallilyticus Vaccinia virus Vibrio fisheri Vaccinia virus modified Ankara Vibrio furnissii Vaccinia virus Western Reserve Vibrio harveyi Varicella zoster virus Vibrio hollisae Variola major virus Vibrio metschnikovii Venezuelan equine encephalitis virus Vibrio mimicus Venezuelan equine encephalitis virus TC-83 Vibrio orientalis Vesicular stomatitis virus Vibrio parahaemolyticus Vibrio cholerae W Western equine encephalitis virus West Nile virus Whitewater Arroyo virus X Xylella fastidiosa Yersinia pestis A1122 Y Yersinia pestis biovar Orientalis strain India 195 Yaba monkey tumor virus Yersinia pestis KIM Yellow fever virus Yersinia pestis (Lcr- strains) Yellow fever virus 17D Yersinia pestis strain pgm- Yersinia enterocolitica Yersinia pseudotuberculosis Yersinia frederiksenii Page 236 of 237

Yersinia intermedia Yersinia rohdei Yersinia pestis Yersinia ruckeri

Toxins and Toxoids

Abrin Clostridium perfringens epsilon toxoid Aflatoxin B1 Conotoxin Aflatoxin B2 Deoxynivalenol Aflatoxin G1 Diacetoxyscirpenol Aflatoxin G2 Diphtheria toxin Agatoxin HT-2 Toxin Anthrax toxin Marine toxins Botulinum Complex Toxoid A Microcystin LR Botulinum Toxoid Neosaxitoxin Botulinum Toxoid B Pertussis toxin Botulinum Toxoid C Ricin Botulinum Toxoid D Ricin A chain Botulinum Toxoid E Saxitoxin Botulinum Toxoid F Shiga toxin 1 and 2 Brevetoxin B pbTx-2 Staphylococcal Enterotoxin A Brevetoxin pbTx-3 Staphylococcal Enterotoxin B Cholera Toxin A subunit Staphylococcal Enterotoxin B toxoid Cholera Toxin B subunit Staphylococcal Enterotoxin C1 Clostridium botulinum neurotoxin Staphylococcal Enterotoxin C2 Clostridium botulinum neurotoxin A Staphylococcal Enterotoxin D Clostridium botulinum toxoids Staphylococcal Enterotoxin E Clostridium perfringens alpha toxoid T-2 Tetraol Tetraacetate Clostridium perfringens beta toxoid T-2 toxin Clostridium perfringens epsilon toxin Tetrodotoxin

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