APPENDIX TABLE of CONTENTS Opinion of the Federal Circuit
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Review of Market for Octane Enhancers
May 2000 • NREL/SR-580-28193 Review of Market for Octane Enhancers Final Report J.E. Sinor Consultants, Inc. Niwot, Colorado National Renewable Energy Laboratory 1617 Cole Boulevard Golden, Colorado 80401-3393 NREL is a U.S. Department of Energy Laboratory Operated by Midwest Research Institute • Battelle • Bechtel Contract No. DE-AC36-99-GO10337 May 2000 • NREL/SR-580-28193 Review of Market for Octane Enhancers Final Report J.E. Sinor Consultants, Inc. Niwot, Colorado NREL Technical Monitor: K. Ibsen Prepared under Subcontract No. TXE-0-29113-01 National Renewable Energy Laboratory 1617 Cole Boulevard Golden, Colorado 80401-3393 NREL is a U.S. Department of Energy Laboratory Operated by Midwest Research Institute • Battelle • Bechtel Contract No. DE-AC36-99-GO10337 NOTICE This report was prepared as an account of work sponsored by an agency of the United States government. Neither the United States government nor any agency thereof, nor any of their employees, makes any warranty, express or implied, or assumes any legal liability or responsibility for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights. Reference herein to any specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise does not necessarily constitute or imply its endorsement, recommendation, or favoring by the United States government or any agency thereof. The views and opinions of authors expressed herein do not necessarily state or reflect those of the United States government or any agency thereof. Available electronically at http://www.doe.gov/bridge Available for a processing fee to U.S. -
Formation of Highly Oxygenated Organic Molecules from Aromatic Compounds
Formation of highly oxygenated organic molecules from aromatic compounds. Ugo Molteni1, Federico Bianchi1-2, Felix Klein1, Imad El Haddad1, Carla Frege1, Michel J. Rossi1, Josef Dommen1, Urs Baltensperger1,* 5 1Laboratory of Atmospheric Chemistry, Paul Scherrer Institute, CH-5232 Villigen, Switzerland 2Department of Physics, University of Helsinki, 00014 Helsinki, Finland Correspondence to: Urs Baltensperger ([email protected]) Abstract 10 Anthropogenic volatile organic compounds (AVOC) often dominate the urban atmosphere and consist to a large degree of aromatic hydrocarbons (ArHC), such as benzene, toluene, xylenes, and trimethylbenzenes, e.g. from handling and combustion of fuels. These compounds are important precursors for the formation of secondary organic aerosol. Despite their recognized importance as atmospheric reactants, the formation of highly oxygenated molecules (HOMs) in the gas phase leading to (extremely) low volatility compounds has not been studied in the past. Here we show that oxidation of 15 aromatics with OH leads to a subsequent autoxidation chain reaction forming HOMs with an O:C ratio of up to 1.09. This is exemplified for five single-ring ArHC (benzene, toluene, o-/m-/p-xylene, mesitylene (1,3,5-trimethylbenzene) and ethylbenzene), as well as two conjugated polycyclic ArHC (naphthalene and biphenyl). We present the identified compounds, differences in the observed oxidation patterns and discuss mechanistic pathways. We report the elemental composition of the HOMs and show the differences in the oxidation patterns of these ArHCs. A potential pathway for the 20 formation of these HOMs from aromatics is presented and discussed. We hypothesize that AVOC may contribute substantially to new particle formation events that have been detected in urban areas. -
In Silico Methods for Drug Repositioning and Drug-Drug Interaction Prediction
In silico Methods for Drug Repositioning and Drug-Drug Interaction Prediction Pathima Nusrath Hameed ORCID: 0000-0002-8118-9823 Submitted in total fulfilment of the requirements for the degree of Doctor of Philosophy Department of Mechanical Engineering THE UNIVERSITY OF MELBOURNE May 2018 Copyright © 2018 Pathima Nusrath Hameed All rights reserved. No part of the publication may be reproduced in any form by print, photoprint, microfilm or any other means without written permission from the author. Abstract Drug repositioning and drug-drug interaction (DDI) prediction are two fundamental ap- plications having a large impact on drug development and clinical care. Drug reposi- tioning aims to identify new uses for existing drugs. Moreover, understanding harmful DDIs is essential to enhance the effects of clinical care. Exploring both therapeutic uses and adverse effects of drugs or a pair of drugs have significant benefits in pharmacology. The use of computational methods to support drug repositioning and DDI prediction en- able improvements in the speed of drug development compared to in vivo and in vitro methods. This thesis investigates the consequences of employing a representative training sam- ple in achieving better performance for DDI classification. The Positive-Unlabeled Learn- ing method introduced in this thesis aims to employ representative positives as well as reliable negatives to train the binary classifier for inferring potential DDIs. Moreover, it explores the importance of a finer-grained similarity metric to represent the pairwise drug similarities. Drug repositioning can be approached by new indication detection. In this study, Anatomical Therapeutic Chemical (ATC) classification is used as the primary source to determine the indications/therapeutic uses of drugs for drug repositioning. -
Lab Standard Operating Procedures (Sops)
QAPP –Watershed Watch Laboratory Assays Revision: 7 Date: September 2020 Appendix A Standard Operation Procedures List of SOPs SOP SOP Revision Description Number Date General Laboratory Safety 001 11/04 1 URI Laboratory Waste Guidebook 001a 09/13 3 URI laboratory Chemical Hygiene Plan 001b 07/04 Laboratory Water 002 11/16 3 General Labware Cleaning Procedure 003 07/19 4 General Autoclave Operation 004 10/18 6 Bottle Autoclaving Procedure 005 01/16 5 Waste Autoclaving Procedure 006 01/16 3 Chlorophyll-A Analysis, Welschmeyer Method 012 04/18 6 Chloride Analysis 013 11/16 5 Ammonia Analysis 014 11/16 5 Orthophosphate and Nitrate + Nitrite Analysis 015 12/16 5 Total Phosphorus and Nitrogen Analysis 016 12/16 5 Salinity Analysis Using a Refractometer 017 11/16 1 Enterococci Analysis Using Enterolert IDEXX Method 018 12/19 4 Analytical Balance Calibration 019 2/06 2 pH Procedure 021 12/19 3 Alkalinity Procedure 022 11/16 2 Filtering Water Samples 023 10/18 2 Fecal coliform Analysis Using Colilert 18 IDEXX 024 01/16 2 Method Laboratory Thermometer Calibration 025 04/19 1 Heterotrophic Plate Count – Quanti-tray 026 05/20 1 Appendix A Standard Operating Procedure 001 Date: 11/04 General Laboratory Safety Revision: 1 Author: Linda Green University of Rhode Island Watershed Watch 1.0 PURPOSE AND DESCRIPTION LAB SAFETY IS EVERYBODY’S JOB! Please be sure to familiarize yourself with these general procedures, as well as the specific handling requirements included in the Standard Operating Procedure (SOP) for each analysis/process. Further general information regarding University of Rhode Island standards for health and safety are found in SOP 001a – University Safety and Waste Handling Document. -
AHFS Pharmacologic-Therapeutic Classification System
AHFS Pharmacologic-Therapeutic Classification System Abacavir 48:24 - Mucolytic Agents - 382638 8:18.08.20 - HIV Nucleoside and Nucleotide Reverse Acitretin 84:92 - Skin and Mucous Membrane Agents, Abaloparatide 68:24.08 - Parathyroid Agents - 317036 Aclidinium Abatacept 12:08.08 - Antimuscarinics/Antispasmodics - 313022 92:36 - Disease-modifying Antirheumatic Drugs - Acrivastine 92:20 - Immunomodulatory Agents - 306003 4:08 - Second Generation Antihistamines - 394040 Abciximab 48:04.08 - Second Generation Antihistamines - 394040 20:12.18 - Platelet-aggregation Inhibitors - 395014 Acyclovir Abemaciclib 8:18.32 - Nucleosides and Nucleotides - 381045 10:00 - Antineoplastic Agents - 317058 84:04.06 - Antivirals - 381036 Abiraterone Adalimumab; -adaz 10:00 - Antineoplastic Agents - 311027 92:36 - Disease-modifying Antirheumatic Drugs - AbobotulinumtoxinA 56:92 - GI Drugs, Miscellaneous - 302046 92:20 - Immunomodulatory Agents - 302046 92:92 - Other Miscellaneous Therapeutic Agents - 12:20.92 - Skeletal Muscle Relaxants, Miscellaneous - Adapalene 84:92 - Skin and Mucous Membrane Agents, Acalabrutinib 10:00 - Antineoplastic Agents - 317059 Adefovir Acamprosate 8:18.32 - Nucleosides and Nucleotides - 302036 28:92 - Central Nervous System Agents, Adenosine 24:04.04.24 - Class IV Antiarrhythmics - 304010 Acarbose Adenovirus Vaccine Live Oral 68:20.02 - alpha-Glucosidase Inhibitors - 396015 80:12 - Vaccines - 315016 Acebutolol Ado-Trastuzumab 24:24 - beta-Adrenergic Blocking Agents - 387003 10:00 - Antineoplastic Agents - 313041 12:16.08.08 - Selective -
Therapeutic Class Overview Anticonvulsants
Therapeutic Class Overview Anticonvulsants INTRODUCTION Epilepsy is a disease of the brain defined by any of the following (Fisher et al 2014): ○ At least 2 unprovoked (or reflex) seizures occurring > 24 hours apart; ○ 1 unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after 2 unprovoked seizures, occurring over the next 10 years; ○ Diagnosis of an epilepsy syndrome. Types of seizures include generalized seizures, focal (partial) seizures, and status epilepticus (Centers for Disease Control and Prevention [CDC] 2018, Epilepsy Foundation 2016). ○ Generalized seizures affect both sides of the brain and include: . Tonic-clonic (grand mal): begin with stiffening of the limbs, followed by jerking of the limbs and face . Myoclonic: characterized by rapid, brief contractions of body muscles, usually on both sides of the body at the same time . Atonic: characterized by abrupt loss of muscle tone; they are also called drop attacks or akinetic seizures and can result in injury due to falls . Absence (petit mal): characterized by brief lapses of awareness, sometimes with staring, that begin and end abruptly; they are more common in children than adults and may be accompanied by brief myoclonic jerking of the eyelids or facial muscles, a loss of muscle tone, or automatisms. ○ Focal seizures are located in just 1 area of the brain and include: . Simple: affect a small part of the brain; can affect movement, sensations, and emotion, without a loss of consciousness . Complex: affect a larger area of the brain than simple focal seizures and the patient loses awareness; episodes typically begin with a blank stare, followed by chewing movements, picking at or fumbling with clothing, mumbling, and performing repeated unorganized movements or wandering; they may also be called “temporal lobe epilepsy” or “psychomotor epilepsy” . -
1-(4-Amino-Cyclohexyl)
(19) & (11) EP 1 598 339 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C07D 211/04 (2006.01) C07D 211/06 (2006.01) 24.06.2009 Bulletin 2009/26 C07D 235/24 (2006.01) C07D 413/04 (2006.01) C07D 235/26 (2006.01) C07D 401/04 (2006.01) (2006.01) (2006.01) (21) Application number: 05014116.7 C07D 401/06 C07D 403/04 C07D 403/06 (2006.01) A61K 31/44 (2006.01) A61K 31/48 (2006.01) A61K 31/415 (2006.01) (22) Date of filing: 18.04.2002 A61K 31/445 (2006.01) A61P 25/04 (2006.01) (54) 1-(4-AMINO-CYCLOHEXYL)-1,3-DIHYDRO-2H-BENZIMIDAZOLE-2-ONE DERIVATIVES AND RELATED COMPOUNDS AS NOCICEPTIN ANALOGS AND ORL1 LIGANDS FOR THE TREATMENT OF PAIN 1-(4-AMINO-CYCLOHEXYL)-1,3-DIHYDRO-2H-BENZIMIDAZOLE-2-ON DERIVATE UND VERWANDTE VERBINDUNGEN ALS NOCICEPTIN ANALOGE UND ORL1 LIGANDEN ZUR BEHANDLUNG VON SCHMERZ DERIVÉS DE LA 1-(4-AMINO-CYCLOHEXYL)-1,3-DIHYDRO-2H-BENZIMIDAZOLE-2-ONE ET COMPOSÉS SIMILAIRES POUR L’UTILISATION COMME ANALOGUES DU NOCICEPTIN ET LIGANDES DU ORL1 POUR LE TRAITEMENT DE LA DOULEUR (84) Designated Contracting States: • Victory, Sam AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU Oak Ridge, NC 27310 (US) MC NL PT SE TR • Whitehead, John Designated Extension States: Newtown, PA 18940 (US) AL LT LV MK RO SI (74) Representative: Maiwald, Walter (30) Priority: 18.04.2001 US 284666 P Maiwald Patentanwalts GmbH 18.04.2001 US 284667 P Elisenhof 18.04.2001 US 284668 P Elisenstrasse 3 18.04.2001 US 284669 P 80335 München (DE) (43) Date of publication of application: (56) References cited: 23.11.2005 Bulletin 2005/47 EP-A- 0 636 614 EP-A- 0 990 653 EP-A- 1 142 587 WO-A-00/06545 (62) Document number(s) of the earlier application(s) in WO-A-00/08013 WO-A-01/05770 accordance with Art. -
Supplementary Information
Supplementary Information Network-based Drug Repurposing for Novel Coronavirus 2019-nCoV Yadi Zhou1,#, Yuan Hou1,#, Jiayu Shen1, Yin Huang1, William Martin1, Feixiong Cheng1-3,* 1Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA 2Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA 3Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA #Equal contribution *Correspondence to: Feixiong Cheng, PhD Lerner Research Institute Cleveland Clinic Tel: +1-216-444-7654; Fax: +1-216-636-0009 Email: [email protected] Supplementary Table S1. Genome information of 15 coronaviruses used for phylogenetic analyses. Supplementary Table S2. Protein sequence identities across 5 protein regions in 15 coronaviruses. Supplementary Table S3. HCoV-associated host proteins with references. Supplementary Table S4. Repurposable drugs predicted by network-based approaches. Supplementary Table S5. Network proximity results for 2,938 drugs against pan-human coronavirus (CoV) and individual CoVs. Supplementary Table S6. Network-predicted drug combinations for all the drug pairs from the top 16 high-confidence repurposable drugs. 1 Supplementary Table S1. Genome information of 15 coronaviruses used for phylogenetic analyses. GenBank ID Coronavirus Identity % Host Location discovered MN908947 2019-nCoV[Wuhan-Hu-1] 100 Human China MN938384 2019-nCoV[HKU-SZ-002a] 99.99 Human China MN975262 -
(12) Patent Application Publication (10) Pub. No.: US 2010/014.3507 A1 Gant Et Al
US 2010.0143507A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/014.3507 A1 Gant et al. (43) Pub. Date: Jun. 10, 2010 (54) CARBOXYLIC ACID INHIBITORS OF Publication Classification HISTONE DEACETYLASE, GABA (51) Int. Cl. TRANSAMINASE AND SODIUM CHANNEL A633/00 (2006.01) A 6LX 3/553 (2006.01) A 6LX 3/553 (2006.01) (75) Inventors: Thomas G. Gant, Carlsbad, CA A63L/352 (2006.01) (US); Sepehr Sarshar, Cardiff by A6II 3/19 (2006.01) the Sea, CA (US) C07C 53/128 (2006.01) A6IP 25/06 (2006.01) A6IP 25/08 (2006.01) Correspondence Address: A6IP 25/18 (2006.01) GLOBAL PATENT GROUP - APX (52) U.S. Cl. .................... 424/722:514/211.13: 514/221; 10411 Clayton Road, Suite 304 514/456; 514/557; 562/512 ST. LOUIS, MO 63131 (US) (57) ABSTRACT Assignee: AUSPEX The present invention relates to new carboxylic acid inhibi (73) tors of histone deacetylase, GABA transaminase, and/or PHARMACEUTICALS, INC., Sodium channel activity, pharmaceutical compositions Vista, CA (US) thereof, and methods of use thereof. (21) Appl. No.: 12/632,507 Formula I (22) Filed: Dec. 7, 2009 Related U.S. Application Data (60) Provisional application No. 61/121,024, filed on Dec. 9, 2008. US 2010/014.3507 A1 Jun. 10, 2010 CARBOXYLIC ACID INHIBITORS OF HISTONE DEACETYLASE, GABA TRANSAMNASE AND SODIUM CHANNEL 0001. This application claims the benefit of priority of Valproic acid U.S. provisional application No. 61/121,024, filed Dec. 9, 2008, the disclosure of which is hereby incorporated by ref 0004 Valproic acid is extensively metabolised via erence as if written herein in its entirety. -
Design, Synthesis, and Evaluation of Antiepileptic Compounds Based on Β-Alanine and Isatin
Design, Synthesis, and Evaluation of Antiepileptic Compounds Based on β-Alanine and Isatin by Robert Philip Colaguori A thesis submitted in conformity with the requirements for the degree of Master of Science Department of Pharmaceutical Sciences University of Toronto © Copyright by Robert Philip Colaguori, 2016 ii Design, Synthesis, and Evaluation of Antiepileptic Compounds Based on β-Alanine and Isatin Robert Philip Colaguori Master of Science Department of Pharmaceutical Sciences University of Toronto 2016 Abstract Epilepsy is the fourth-most common neurological disorder in the world. Approximately 70% of cases can be controlled with therapeutics, however 30% remain pharmacoresistant. There is no cure for the disorder, and patients affected are subsequently medicated for life. Thus, there is a need to develop compounds that can treat not only the symptoms, but also delay/prevent progression. Previous work resulted in the discovery of NC-2505, a substituted β-alanine with activity against chemically induced seizures. Several N- and α-substituted derivatives of this compound were synthesized and evaluated in the kindling model and 4-AP model of epilepsy. In the kindling model, RC1-080 and RC1-102 were able to decrease the mean seizure score from 5 to 3 in aged mice. RC1-085 decreased the interevent interval by a factor of 2 in the 4-AP model. Future studies are focused on the synthesis of further compounds to gain insight on structure necessary for activity. iii Acknowledgments First and foremost, I would like to thank my supervisor Dr. Donald Weaver for allowing me to join the lab as a graduate student and perform the work ultimately resulting in this thesis. -
11.8 Aromatic Compounds Aromatic Compounds Naming Aromatic
11.8 Aromatic Compounds In 1825, Michael Faraday isolated a hydrocarbon called benzene, which consists of a six-carbon ring with alternating double bonds and has the molecular formula C6H6. Learning Goal Describe the bonding in benzene; name aromatic compounds, and draw their skeletal formulas. Chemistry: An Introduction to General, Organic, and Biological Chemistry, Twelfth Edition © 2015 Pearson Education, Inc. Aromatic Compounds Benzene is • an aromatic compound • a ring of six C atoms, each bonded to one H atom • a flat ring structure drawn with three alternating double bonds • represented by two structures because the electrons are shared equally among all the C atoms • represented by a skeletal formula using a circle in the center instead of the alternating double bonds Chemistry: An Introduction to General, Organic, and Biological Chemistry, Twelfth Edition © 2015 Pearson Education, Inc. Naming Aromatic Compounds Aromatic compounds containing a benzene ring and a single substituent are named as benzene derivatives. Since the ring contains only one substituent, the ring is not numbered. Some common names such as toluene, aniline, and phenol are allowed by IUPAC rules. Chemistry: An Introduction to General, Organic, and Biological Chemistry, Twelfth Edition © 2015 Pearson Education, Inc. 1 Naming Aromatic Compounds When there are two or more substituents, the benzene ring is numbered to give the lowest numbers to the substituents. Chemistry: An Introduction to General, Organic, and Biological Chemistry, Twelfth Edition © 2015 Pearson Education, Inc. Naming Aromatic Compounds When a common name such as toluene, phenol, or aniline can be used, • the carbon atom attached to the methyl, hydroxyl, or amine group is numbered as carbon 1 • the other substituents are named alphabetically Chemistry: An Introduction to General, Organic, and Biological Chemistry, Twelfth Edition © 2015 Pearson Education, Inc. -
Dihydro-3H-1,2,4-Triazole-3-Thione (TP-315)—A New Anticonvulsant Drug Candidate—On Living Organisms
International Journal of Molecular Sciences Article Effect of Chronic Administration of 5-(3-chlorophenyl)-4-Hexyl-2,4 -Dihydro-3H-1,2,4-Triazole-3-Thione (TP-315)—A New Anticonvulsant Drug Candidate—On Living Organisms Anna Makuch-Kocka 1,* , Marta Andres-Mach 2, Mirosław Zagaja 2, Anna Smiech´ 3 , Magdalena Pizo ´n 4 , Jolanta Flieger 4, Judyta Cielecka-Piontek 5 and Tomasz Plech 1 1 Department of Pharmacology, Faculty of Health Sciences, Medical University of Lublin, 20-093 Lublin, Poland; [email protected] 2 Isobolographic Analysis Laboratory, Institute of Rural Health, 20-090 Lublin, Poland; [email protected] (M.A.-M.); [email protected] (M.Z.) 3 Sub-Department of Pathomorphology and Forensic Veterinary Medicine, Department and Clinic of Animal Internal Diseases, University of Life Sciences in Lublin, 20-612 Lublin, Poland; [email protected] 4 Department of Analytical Chemistry, Faculty of Pharmacy, Medical University of Lublin, 20-093 Lublin, Poland; [email protected] (M.P.); jolanta.fl[email protected] (J.F.) 5 Department of Pharmacognosy, Faculty of Pharmacy, Poznan University of Medical Sciences, 61-781 Pozna´n,Poland; [email protected] * Correspondence: [email protected] Citation: Makuch-Kocka, A.; Andres-Mach, M.; Zagaja, M.; Smiech,´ Abstract: About 70 million people suffer from epilepsy—a chronic neurodegenerative disease. In A.; Pizo´n,M.; Flieger, J.; most cases, the cause of the disease is unknown, but epilepsy can also develop as the result of a Cielecka-Piontek, J.; Plech, T. Effect of Chronic Administration of stroke, trauma to the brain, or the use of psychotropic substances.