Bioengineering

M. F. Insana, Interim Department Head cooperation among individuals trained in different 3120 Digital Computer Laboratory disciplines. 1304 West Springfield Avenue MC-278 • The program has great strength in medical and biological Urbana, IL 61801 imaging, including ultrasound, MRI, fMRI, optical 217-333-1867 coherence tomography, and fluorescence dynamics, as http://www.bioen.uiuc.edu well as contrast agents to assist many imaging [email protected] modalities. • A program of bioacoustic studies draws heavily on The newly formed Department of Bioengineering researchers with backgrounds in electrical engineering, (December 2003) has completed its startup phase, having physiology, biophysics, and medicine. grown to six faculty members and admitting four classes • Bioinformatics studies are carried out by bioengineers, of undergraduate students (total 112) and graduate students physiologists, microbiologists, and crop scientists. (total 30). It now begins a phase of integrating with and • There are projects in neural engineering, including leveraging campus strengths related to bioengineering, electrode array technology development, neural guidance, beginning with biomedical imaging science and extending computational models, and hearing aids. to cellular and molecular engineering, with likely foci in • A strong effort in cellular biomechanics includes molecular imaging, animal models of disease, nano/micro development of novel fluorescence sensors for monitoring biosensors, and functional genomic modeling. Plans call intracellular signaling pathways. for growth to 16 faculty members, 100 graduate students, • Faculty from many departments are involved in studies and 250 undergraduate students in the next several years. of the properties of normal and diseased bones, orthopedic Bioengineering has a large number of affiliate faculty, implants, immune response, and biomechanics. most of whom have contributed to the nondepartmental • Computational bioengineering includes simulation and program that existed for the previous 30 years of informatics. bioengineering research. However, this number has grown • Bioengineering simulation studies are conducted by with the addition of bioengineering focused faculty in other physicists, chemists, physiologists, integrative biologists, departments and the redirection of research efforts to electrical engineers, and computer scientists. bioengineering by existing Illinois faculty. Thus, there is a • Other areas of research, such as bioinstrumentation, strong base of bioengineering research on campus, much biomaterials, comparative biomedicine, and radiation of which is captured in this Summary report. studies, also require researchers with similar interests but Bioengineering brings to the study of biology and differing fields of expertise. medicine the methods of inquiry—both analytical tools and the design approach—that have been the A significant amount of the bioengineering research underpinnings of engineering and the physical sciences. activity at the University of Illinois is carried out at the Bioengineers seek to better understand biological Beckman Institute for Advanced Science and Technology phenomena and living systems, to create new instruments and at the Institute for Genomic Biology, where and techniques to deal with biologically and medically interdisciplinary work is nurtured and promoted. oriented problems, and ultimately to improve the human The broad scope of research activities described here condition. reflects the interests of participating faculty and students Bioengineering research is conducted by the faculty, currently involved in the field. Graduate education in students, and staff of the College of Engineering as well as bioengineering is closely associated with the various the colleges of Veterinary Medicine; Applied Health research projects described. The research projects Sciences; Agricultural, Consumer, and Environmental conducted in the College of Engineering are also included Sciences; Medicine; and Liberal Arts and Sciences in their respective departmental sections of the Summary (schools of Chemical Sciences, Molecular and Cellular of Engineering Research. Biology, and Integrative Biology). The projects are interdisciplinary in nature and require, in many cases, close

1 Jianjun Cheng Faculty and Their Interests Biomaterials, polymers, gene delivery, nanomedicine, self-assembly Narayan R. Aluru Bioengineering, computational science and engineering, Robert Clegg engineering mechanics, fluid dynamics, nano-, micro-, and Experimental biophysics with an emphasis on kinetics and meso-technology optical spectroscopy

Thomas J. Anastasio Brian Cunningham Computational neuroscience Nanotechnology, photonic crystals, biosensors, micro/ nanofabrication methods and materials detection Rashid Bashir instrumentation BioMEMS and biosensors, bionanotechnology, nanomedicine, applications of MEMS and nanotechnology Howard S. Ducoff, Emeritus in medical and biological problems, multiscale tissue Radiation biophysics engineering. Albert S. Feng Philip M. Best Sound communication, pattern recognition, and Ion channels localization; computational neuroscience; neuroengineering Rohit Bhargava Infrared spectroscopic imaging, automated and Leon A. Frizzell, Emeritus quantitative histopathology, cancer pathology, Ultrasonic biophysics, ultrasonic bioengineering macromolecular dynamics in composites, molecular and tissue engineering, nanotechnology, biophotonics John G. Georgiadis instrumentation and algorithms Bioengineering, computational science and engineering, energy systems and thermodynamics, fluid dynamics, heat Stephen Boppart transfer, nano-, micro-, and meso-technology Optical biomedical imaging, molecular imaging, lasers in medicine and biology, optical coherence tomography, Steve Granick image-guided surgery, medical engineering, optical Polymers and biopolymers, nanorheology/tribology, diagnostics of cancer surface spectroscopies

Richard D. Braatz William T. Greenough Multiscale systems and control Neuronal pattern analysis

Yoram Bresler Dominique J. Griffon Biomedical imaging systems; statistical signal and image Applications of biomaterials in orthopedic surgery processing; inverse problems; statistical pattern recognition; sensor-array processing Bruce M. Hannon Biological modeling Bertram C. Bruce K-12 and university science education, technologies for Elizabeth Hsiao-Wecksler learning, community informatics Bioengineering, control systems, dynamic systems, engineering mechanics Sahraoui Chaieb Bioengineering, computational science and engineering, Michael Insana engineering mechanics, fluid dynamics, materials Development of novel ultrasonic instrumentation and behavior, nano-, micro-, and meso-technology methods for imaging soft tissue microstructure, elasticity, and blood flow John C. Chato, Emeritus Bioengineering, energy systems and thermodynamics, heat Eric G. Jakobsson transfer Computational biology and nanoscience

2 Iwona Jasiuk William D. O'Brien, Jr. Solid mechanics; biomechanics; mechanics of materials; Ultrasonic biophysics and bioeffects, acoustic microscopy, micromechanics; composite, biological and nano- ultrasonic bioengineering, ultrasonic dosimetry, ultrasonic materials; bone mechanics; composite interfaces; elasticity tissue characterization, acoustic imaging techniques

Amy Wagoner Johnson Michael L. Oelze Synthetic biomaterials, failure mechanics of metals and Ultrasound, including backscatter microscopy, biomaterials quantitative imaging, computed tomography; use of ultrasound for cancer diagnosis and therapy; bioeffects of Neil L. Kelleher ultrasound; sonoporation; coded excitation and ultrasound Mass spectrometry, enzymology, "Top Down" proteomics, natural products Daniel W. Pack Drug and gene delivery systems Kyekyoon (Kevin) Kim Growth of GaN-based compound semiconductors and Adrienne L. Perlman fabrication of optoelectronic and electronic devices using Normal and disordered deglutition plasma-assisted MBE; plasma-arc-driven electromagnetic railgun for fueling of plasma devices; charged liquid Gerald J. Pijanowski cluster beam generation and application to thin film Orthopedic biomechanics deposition, micropattern generation, and nanoparticle fabrication; generation of solid and hollow, charged and Nathan D. Price neutral, monodisperse, micro- and nanospheres for Systems biology, cancer, model-guided cellular biomedical and other applications; plasma display panels; engineering, microbial biofuel production development of novel thin film deposition techniques using plasmas, charged particles, electrostatic spraying, Klaus Schulten and their combinations with other techniques; MEMS and Theoretical biological and computational physics, sensors; ionized source (cluster) beam deposition for low- statistical physics temperature growth of high-quality films; inertial confinement fusion targets Mark A. Shannon Bioengineering, combustion and propulsion, Waltraud M. Kriven computational science and engineering, energy systems Phase transformations in oxide ceramics (TEM, high-temp and thermodynamics, heat transfer, materials processing, XRD, and synchrotron), geopolymers, processing- nano-, micro-, and meso-technology microstructure-property relations in structural ceramics and composites, synthesis of oxide fibers, bioceramics, Bradley Sutton electron microscopy Functional magnetic resonance imaging, MR pulse sequence design, dynamic imaging for speech, diffusion Deborah E. Leckband weighted imaging, functional spectroscopic imaging Bioengineering and biophysics Jonathan V. Sweedler Zhi-Pei Liang Neurotransmitter distribution and release Magnetic resonance imaging, pattern recognition, statistical learning, bioinformatics Kimani C. Toussaint Optical microscopy, optical polarization control, Manssour H. Moeinzadeh nanophotonics, biophotonics Biomechanics, dynamic modeling, experimental mechanics Ning Wang Cytoskeletal biomechanics, machanotransduction, bio- Mark E. Nelson imaging of cytoskeletal structures and stress distribution in Computational neuroscience living cells

3 Yongmei Michelle Wang Biomedical imaging and biomedical image/signal Bioacoustics analysis, structural and functional neuroimage analysis, Biomolecular Cochlear Implants multi-model integration of neuroimaging data A. S. Feng,* R. Kollmar, B. C. Wheeler, M. Novak, Yingxiao Wang S. Shah Molecular imaging of live cell dynamics, molecular and University of Illinois Research Board; Mary Jane Neer cellular engineering, nanotechnology, biophotonics Foundation; National Organization of Hearing Research Conducted in the Beckman Institute for Advanced Science Matthew B. Wheeler and Technology Tissue engineering, microfluidics, nanometer-scale integrated systems, biology of single mammalian embryos, The overall goal of this project is to develop high- embryonic and adult stem cells, drug delivery, remote resolution biomolecular cochlear implants using state-of- sensing of embryo metabolism and embryonic health, the-art molecular biological, microfluidic, and NMR imaging, microcalorimetry and MEMS actuators bioengineering techniques. High-Intensity Ultrasound for Prostate Treatment Bruce C. Wheeler L. A. Frizzell,* J. S. Tan, G. M. Warren Analysis of multichannel neural signals, microminiature [email protected] sensors for neural recording, algorithms for enhanced National Institutes of Health, CA81340; SBC Interscience hearing aids, patterned growth of neurons Research, Inc.

Gerard C. L. Wong Conducted in the Beckman Institute for Advanced Science Biopolymers, biomolecular materials, biological and and Technology biomimetic self-assembly, gene therapy, synchrotron x-ray In this study, ultrasound phased arrays are being developed probes for high intensity ultrasound treatment of prostate disease. These arrays will allow electrical scanning of the focus and James F. Zachary will replace currently used transducers that must be Ultrasound-induced bioeffects, contrast-agent induced mechanically scanned. The design will use a cylindrically bioeffects, and acoustic imaging of tumors shaped array with elements larger than a wavelength to keep the number of elements to a reasonable level and Yuanhui Zhang thereby reduce the cost and complexity of manufacture. Indoor air quality; effect of indoor air quality on occupants; The goal is to determine an optimal design that will sensor technology for bioenvironmental systems; heating, minimize the effects of grating lobes by varying the ventilation, and air-conditioning control; waste treatment spacing and size of the elements. Huimin Zhao Ultrasonic Elasticity Imaging of the Breast Biomolecular Engineering and Biotechnology M. F. Insana,* J. Liu, K.-S. Kim, S. Kalyanam National Institutes of Health; National Cancer Institute, Sheng Zhong R01 CA082497 Systems biology and bioinformatics Conducted in the Beckman Institute for Advanced Science and Technology The objective of the research is to develop a new form of ultrasonic imaging that is more sensitive specifically to the presence of breast neoplasms than x-ray mammography. We develop instrumentation with an industrial partner, write new image reconstruction software, construct novel tissue-like phantom media for testing, and apply these techniques on patients. The goals are to understand how mechanical properties indicate disease and then develop new instruments for effective new diagnosis.

* Denotes principal investigator.

4 Oscillation in the Central Auditory System: Roles in close to certain modern military weapons platforms Hearing approach 150 dBA. At these levels, the attenuation A. S. Feng;* W. Y. Lin, S. C. Yang provided by hearing protection devices (HPDs) is limited National Institutes of Health, R01 DC04998 by bone-conducted sound that bypasses the ear canal and its associated protection (earplugs and earmuffs). An Conducted in the Beckman Institute for Advanced Science improved understanding of the transmission mechanisms and Technology for bone-conducted sound is required to enable the design The overall goal of this project is to gain insight into the of improved active and passive hearing protection devices. cellular mechanisms that underlie rapid periodic firing of Creare and the University of Illinois propose a three- single neurons in the bat and frog inferior colliculus, and pronged approach to investigate the transmission of bone- into its functional significance in sound communication. conducted sound and design-improved HPDs. The Evaluation of Acoustic Propagation Paths into the approach involves calculation, using an acoustic wave Human Head propagation model implemented in finite element analysis W. D. O’Brien, Jr.;* C. R. Lansing, software; simulation, using an instrumented physical R. D. Chambers (Speech & Hearing Sci.); L. M. Brault, model of a human head; and human subject tests, W. Han, M. G. Wismer (Bucknell Univ.); J. A. McNew, investigating the nonlinear response of the cochlea to bone A. A. Bellina conduction stimulation. In Phase I, we propose to [email protected] demonstrate the feasibility of each of these techniques. In U.S. Air Force Office of Scientific Research, Phase II, we will conduct a detailed investigation of the FA9550-06-1-0128 phenomena using these techniques and apply the results to the next generation of hearing protection devices. Conducted in the Beckman Institute for Advanced Science and Technology Quantitative Ultrasound Imaging of the Breast W. D. O’Brien, Jr.,* M. L. Oelze; The objective is to develop an understanding, based on first D. G. Simpson (Statistics); principles, of the reception and conduction paths of very- T. A. Bigelow (University of North Dakota); M. N. Do, high-amplitude air-borne sound levels (about 150 dB) to M. R. King, A. Haak, D. P. Hruska, R. J. Miller, the inner ear by soft and hard tissues in order to design an J. P. Blue, Jr., J. L. King; S. Sarwate (Pathology); advanced hearing protector device. The computational T. J. Hall, J. A. Zagzebski, goal is to develop an acoustic propagation model using E. L. Madsen (University of Wisconsin); W. D. O'Brien well-understood and documented computational [email protected] techniques that will model propagated acoustic signals National Institute of Health, National Cancer Institute, around and inside the human head. Modeling of acoustic R01 CA111289 diffraction around stationary and moving complex geometries will be accomplished with finite-element Conducted in the Beckman Institute for Advanced Science analysis (FEA). This model will take into consideration the and Technology effects of diffraction of sound around the human head, and The long-term goal of the Bioengineering Research the direction from which the sound has traveled from the Partnerships (BRP) (between the University of Illinois and acoustic source to the human head. the University of Wisconsin) is to develop, unify, refine, Hearing Protection for High-Noise Environments and implement a fundamentally new approach to W. D. O’Brien, Jr.,* M. G. Wismer (Bucknell Univ.), quantitative ultrasound (QUS) imaging of biological J. A. McNew, A. A. Bellina tissues and mammary tumors by the quantification of tissue [email protected] microstructure through acoustic backscatter. The overall U.S. Air Force Office of Scientific Research, STTR AF06- hypothesis is that a set of QUS parameters can significantly T035; SBC: Creare, Inc. improve breast lesion differentiation and classification. The primary QUS parameters to be exploited include Conducted in the Beckman Institute for Advanced Science attenuation, scatterer size, scatterer number density, and and Technology acoustic concentration (scatterer number density times Hearing protection for personnel working in high-noise their impedance change). environments remains an important challenge for the scientific and engineering community. The sound levels

* Denotes principal investigator.

5 Ultrasound-Induced Tissue Damage Assessment to enhance cell permeabilization. With this method it is W. D. O’Brien, Jr.;* M. L. Oelze; D. G. Simpson (Stat.); possible, by using ultrasound and contrast microbubbles, J. E. Erdman, Jr. (Food Sci. & Human Nutr.); to deliver therapeutic compounds noninvasively into M. M. Forbes, C. A. Johnson, Z. T. Hafez (Bioengr.); specific target cells. J. L. King, R. J. Miller, J. P. Blue, Jr., Inertial Cavitation and Neovascularization S. Sarwate (Pathology) W. D. O'Brien, Jr.,* M. L. Oelze, [email protected] C. A. Johnson (Bioengr.), R. J. Miller, J. P. Blue National Institutes of Health, National Institute of Beckman Institute for Advanced Science and Technology Biomedical Imaging and Bioengineering, R37 EB002641 The objective of this interdisciplinary research project is to Conducted in the Beckman Institute for Advanced Science examine and characterize how the interaction of a contrast and Technology agent with ultrasound alters the expression of vascular The proposed research program is a basic science growth factor molecules following capillary injury. The (nonclinical) investigation of a potentially significant generation of these data will allow for a more clear ultrasound (US)-induced biological effect; that is, whether understanding of the safety issues surrounding the use of the application of ultrasound contrast agents (UCAs) in ultrasound contrast agents to assess blood flow and humans adversely affects the vasculature. The medical myocardial perfusion in human patients. Microbubble profession benefits if it is shown that diagnostic US is a ultrasound contrast agents are valuable diagnostic tools for significant medical risk to the patient—by advising physicians, but their use must be considered in the context clinicians about this risk, and suggesting how the clinician of risk-benefit assessment for each patient. The medical can monitor the degree of risk. Likewise, the medical significance of and long-term potential benefits from the profession benefits if it is shown that diagnostic US is not use of ultrasound contrast agents are clear; however, a significant medical risk to the patient—by eliminating concerns related to their “safe use” have been raised this as a clinical concern. In either case, there is clear because of reports of microbubble ultrasound contrast medical significance. The data necessary to decide this agent-induced vascular injury. Currently, the medical issue are not currently available. Today we are faced with significance and pathogenesis of such phenomena are not a significant challenge about the human use of UCAs; that clearly understood. Because ultrasound contrast agents are is, the lack of knowledge of whether the interaction of US poised to be used to assess myocardial and skeletal muscle with UCAs is a significant medical problem in humans. perfusion, the results of our study are an early step in FDA is also uncertain about the safety and/or effectiveness developing an understanding of the primary bioeffects of UCAs and is waiting until more is known about the risk (injury) of ultrasound contrast agent on capillary beds of of these agents before approving new UCAs, thus denying the heart and circulatory system. their well-known benefits to the patient. Ultrasound Contrast Agents; Dynamic Physical Evaluation of Inertial Cavitation's Role in Behavior and Bioeffects Sonoporation W. D. O'Brien, Jr.,* W. D. O'Brien, Jr.,* M. M. Forbes (Bioengr.), S. L. Bridal (Université Pierre et Marie Curie, D. A. King (Mech. Sci. & Engr.) UMR C.N.R.S. 7623, Paris), A. Haak, Internal Funds D. A. King (Mech. Sci. & Engr.) University of Illinois-Centre National de Las Recherche The objective of this interdisciplinary research project is to Scientifique Collaborative Research Program examine and characterize how the interaction of a contrast agent with ultrasound alters the cell membrane to large Conducted in the Beckman Institute for Advanced Science molecules. A significant problem in cancer therapy is the and Technology compromised quality of life experienced by the patient due The objective of the program is to develop a collaborative to the side effects of the therapeutic compounds. Delivery interaction between the two research groups that will of molecular medicine to solid tumors is often inefficient investigate the physical interaction mechanisms between and as a result, the patient’s healthy cells and tissues are ultrasound and contrast agents. The two research programs subject to the toxic effects of the drugs. Thus, it is important are the Bioacoustics Research Laboratory, Department of to develop approaches that deliver drugs to the appropriate Electrical and Computer Engineering, University of cells within the patient in a way that is specific, efficient, Illinois and Laboratoire d'Imagerie Paramètrique, and safe. One such method involves the use of ultrasound Université Pierre et Marie Curie–Paris 6, Paris, France.

* Denotes principal investigator.

6 Both research programs have contributed significantly to Tumor Diagnosis through Enhanced Ultrasound the capabilities of diagnostic imaging. During the last Imaging decade, ultrasonic contrast agents have provided clinical M. L. Oelze,* J. F. Zachary (Vet. Pathobiol.), ultrasonic imaging with a new and powerful capability to W. D. O'Brien, Jr. image structures not previously possible. These agents are [email protected] made of small microbubbles (< 5 µm in diameter) that are National Institutes of Health, National Cancer Institute, administered into the vascular system of the body to F32CA96419 enhance ultrasound image contrast. Ultrasound contrast Conducted in the Beckman Institute for Advanced Science agents are used as adjuncts in routine ultrasound and Technology evaluations to enhance sonographic contrast and thus increase the opportunity for early detection, diagnosis, and The objective is to develop and refine a fundamentally new treatment of a variety of disease processes including heart approach to enhance ultrasound imaging of biological disease and cancer. Concerns about the potential bioeffects tissues by the quantification of tissue microstructure of inertial cavitation associated with the interaction of through acoustic backscatter. This enhanced imaging ultrasound with contrast agents in human beings have been technique will then be adapted for real-time in situ clinical reported. The center topic involved in this cooperative diagnosis of solid tumors with the expectation of producing program between the two research programs is the acoustic images that will provide an accurate diagnosis of connection between bioeffects and the bubbles responses cancer. Use of enhanced ultrasound imaging is medically to ultrasonic insonification. significant because it offers a quick and noninvasive means of detecting and classifying tumor types. Biomaterials Characterization with High-Frequency Ultrasound Computed Tomography M. L. Oelze* Biochemical and Biomedical [email protected] 3M Corporation Engineering

Conducted in the Beckman Institute for Advanced Science Modeling and Design of Controlled-Release Drug and Technology Delivery Systems The objective is to evaluate diffraction tomography R. D. Braatz,* D. W. Pack,* A. N. Ford, M. Kishida algorithms applicable to soft tissue scattering, construct a National Institutes of Health; U.S. Department of Energy high-frequency ultrasound computed tomography Controlled-release drug delivery systems can provide scanning device, and evaluate model biological systems for therapeutic benefits while reducing side effects and scanning. An ultrasound frequency of up to 100 MHz reducing the frequency of administrations. However, the yielding resolution of 12 to 15 micrometers will be used. design of controlled-release systems can be challenging Elastic properties of cell models, other kinds of tissues, and due to incomplete understanding of the mechanisms that synthetic biomaterials will be imaged and quantified. The regulate release. We are modeling the effects of polymer high-resolution, quantitative information that the high- particle size distribution, molecular weight distribution, frequency ultrasound computed tomography device can pore size distribution, and the accumulation of acidic yield will be beneficial for many kinds of research into degradation byproducts on macromolecule release in properties and functioning of materials. biodegradable polymer drug delivery systems. A model- based optimization algorithm will be developed to design drug delivery systems to produce desired release profiles. Cross-Talk between Integrins and Cadherins in Tumorigenesis P. J. A. Kenis, D. E. Leckband,* J. Silvestre National Institutes of Health, PHS 1 F31CA126500 Cell-surface and cell-cell receptors have been studied extensively to investigate the switch from benign noninvasive to metastatic tumors. However, one of the major limitations has been the lack of studies that explore the effect of the cellular microenvironment on this

* Denotes principal investigator.

7 transition. In this study we use microfluidic platforms to biology techniques. Our findings are providing critical create gradients of surface-bound extracellular matrix insights into the connections between protein mutations (ECM) and N-/E-cadherin proteins, thereby manipulating and human disease. the microenvironment that the cell experiences. Cell Smart Materials for Biomedical Applications migration studies on these gradients are elucidating D. E. Leckband,* C. Mann, X. Zhu, K. Plunkett, J. More, synergies between integrins and cadherins, and thereby N. Wang increasing our understanding of the effects of the tumor National Science Foundation, BES 0349915 microenvironment and gene expression on metastasis. This work focuses on the design of biologically active Cadherin Glycoslation in Oral Cancer materials for cell culture. This program has two main M. Kukurizinska (Boston Univ.), D. E. Leckband, thrusts. The first is to identify the design parameters that M. Langer control the interactions of temperature-responsive polymer National Institutes of Health coatings with biological macromolecules and cells. The Cadherins are essential for development and tissue second related research objective is to develop novel organization. Their malfunction is also linked to a variety microfabrication methods for generating tunable, of different cancers. In some oral cancers, cadherins biomaterials with variable mechanical compliance and express an unusually high level of carbohydrate interfacial properties. These materials will enable the modification. However, whether this is the basis of the identification of both mechanical and surface properties disease or a consequence has not been established. The goal biomaterials that control cell attachment and function in of this project is to determine the impact of abnormal engineered environments. cadherin glycosylation on cadherin function, and to Design and Synthesis of Polymeric Materials for DNA determine whether these changes alter the cadherin Delivery function and thereby contribute to carcinogenesis. D. W. Pack,* D. Drake, N. Gabrielson, V. Shum, Mechanocoupling at Intercellular Junctions M. E. Hwang D. E. Leckband,* N. Wang (Mech. Sci. & Engr.), National Science Foundation, BES-0134163; Siteman F. Chowdury, C. Mann, Q. Shi Center for Cancer Nanotechnology Excellence; University National Institutes of Health, RO1 GM51338 Reid T. of Illinois Milner Professorship (Q. Shi) The goal of this project is to design novel polymers capable We are using magnetic twist cytometry and traction force of safe and efficient delivery of genetic material to microscopy to determine the molecular mechanisms of mammalian cells. A first step of this research is to elucidate transmembrane force transduction and signaling at the structure-function relationships of currently available, intercellular junctions. These studies are identifying off-the-shelf gene-delivery polymers. Thus, researchers mechanical components that couple adhesion receptors to are developing quantitative assays that will allow the team the cytoskeleton and enhance adhesive strength through to probe the various intracellular barriers to transport of mechano-chemical feedback. DNA from outside the cell into the nucleus. The resulting structure-function database will provide a basis for Nanomechanics of Biological Adhesion: from Single intelligent design of new materials with improved safety Molecules to Tissues and efficacy. D. E. Leckband,* V. Maruthamuthu, Y.-H. Chien, Q. Shi National Institutes of Health, RO1 GM51338; Drickamer Design of Materials for Delivery of Small-Interfering Graduate Fellowship (VM) RNA D. W. Pack,* L. Wong In these studies, we are determining the molecular basis of American Cancer Society protein-mediated cell-cell adhesion in tissues. Receptor- mediated cell adhesion is important in wound healing, RNA interference is an emerging technology in which cancer metastasis, and tissue engineering. This work uses small, interfering RNA (siRNA) sequences mediate highly a multiscale approach to establish how the detailed specific shutdown of gene expression. Because many nanomechanics of protein bonds governs the mechanics cancers are caused by undesirable expression of a specific and formation dynamics of intercellular junctions in gene (an oncogene) or abnormally high expression of a tissues. We use a combination of molecular force probe normal gene, RNAi holds the potential to become a new measurements, theoretical modeling, and molecular class of anticancer therapy. Safe and efficient delivery of

* Denotes principal investigator.

8 siRNA molecules is the highest hurdle holding back the BBB and in vivo models to investigate the ability of development of RNAi-based therapies. The goal of this nanoparticles to provide prolonged delivery of drugs to the project is to learn how to design polymers to efficiently brain. carry siRNA into tumor cells. The research team Precision-Release Drug Delivery investigates how specific properties of polymers control D. W. Pack,* K. Stovall, K. Smith cytoplasmic localization and release of siRNA. The National Institutes of Health physicochemical properties of polymers and their complexes with siRNA are evaluated, and gene The research team is encapsulating therapeutic compounds knockdown is investigated in cells growing in culture and in polymer matrices such that the drug can be released at a in animal models. controlled rate over a prolonged period of time in the body. The approach is unique in that researchers have precise Engineering of Viruses for Enhanced Gene Therapy control over particle size, size distribution, and D. W. Pack,* R. Keswani, D. Drake architecture. These characteristics lead to unprecedented National Science Foundation, BES-0602636 control of drug delivery kinetics. Furthermore, the team is The overall goal of this project is to develop a new class of pursuing advanced applications, such as passive targeting gene delivery vectors by combining “bald” retrovirus-like based on particle size, that have not previously been particles (RVLPs) and synthetic components. RVLPs are possible due to the limitations of current fabrication essentially intact virions, but lack the viral envelope methods. protein that is responsible for binding to target cells and for Decoding the Secretome for Systems Analysis of virus-cell membrane fusion. RVLPs are therefore Glioblastoma noninfectious. Synthetic polycations—polymers or lipids N. D. Price,* J. Sung, J. A. Eddy, S. Gupta, —can electrostatically “complex” with RVLPs to L. B. Edelman, J. Dolivo reintroduce cell binding and membrane fusion. In addition, University of Illinois conjugation of appropriate ligands to the synthetic component provides cell-specific targeting. Once inside We are performing a set of fundamental experiments in the cell, the natural virus mechanisms, provided by the glioblastoma cell lines to assess the degree to which the RVLP, take over to provide efficient intracellular secretome can be used to identify causal genetic trafficking and even integration of genes with the host perturbations and to provide information about the state of genome providing stable expression. Preliminary results biomolecular networks. Specific aims are to generate demonstrate the feasibility of hybrid nanovectors for profiles of the secretome in glioblastoma cell lines for efficient gene delivery. This project is laying a foundation specific siRNA knockdowns and drug treatments to for design and optimization of hybrid vectors, especially discover the extent to which specific perturbations are for targeted gene therapies. reproducibly and uniquely identifiable in the secretome; to generate a predictive genetic regulatory network; and to Nanoparticles for Brain Drug Delivery generate a predictive computational model linking D. W. Pack,* S. Anthony observed patterns in the secretome to likely causal genetic Parkinson's Disease Foundation perturbations (or, at a more-coarse level of resolution The brain is isolated from the systemic circulation by the identify likely perturbed "pathways"). We have initial blood-brain barrier (BBB), formed by the very tight "proof of concept" of this approach using novel junctions between brain capillary endothelial cells. As a computational methods integrated with a previously result, most water-soluble drugs, especially available model and data from a model organism, macromolecules, cannot be effectively delivered to the Halobacterium. We will study various glioblastoma and brain from the circulation. Safe and effective delivery glial (noncancerous) cell lines, including the very systems are desperately needed for brain drug delivery, in important subpopulation of cancer stem cells (CD133+), particular for novel treatments of neurological diseases thought to be the primary drivers of tumor growth and (e.g., Parkinson’s and Alzheimer’s diseases) and brain regeneration. cancer. The overall goal of this project is to investigate biodegradable polymer nanoparticles as vehicles for drug delivery to the brain. Nanoparticles are covalently derivatized with targeting ligands that can be transported across the BBB. The team uses both in vitro models of the

* Denotes principal investigator.

9 Model-Guided Cellular Engineering of C. beijerinckii translation (REST), which we use to map observed protein for Increased Biobutanol Production signatures to identify likely ranges of states of internal N. D. Price,* C. Milne, R. Raju, H. Blaschek genetic network states. University of Illinois Biomolecular Engineering via Directed Evolution With the completion of the genome sequence of C. H. Zhao,* M. McLachlan, V. Gonzalez beijerinckii, we can now employ the tools of systems National Science Foundation CAREER biology to gain increased insight into the metabolic and The team is interested in developing a novel receptor-based regulatory networks relevant to solvent production. gene expression system in which activity can be precisely Transcriptional analysis from Hans Blaschek's lab using a regulated by a synthetic ligand. We will use a combined 500 gene microarray of the C. beijerinckii 8052 parent and rational design and directed evolution approach to engineer the hyper-butanol producing BA101 strains during the shift a fully orthogonal ligand–receptor pair consisting of an from acidogenesis to solventogenesis revealed significant estradiol derived synthetic ligand and a human estrogen differences between the two strains with respect to the receptor ligand binding domain mutant. Such a system is transcription of genes in multiple functional classes that are an invaluable tool for gene therapy, temporal control of the necessary for solventogenesis, sporulation, motility, and onset of phenotypes in transgenic animals, regulated sugar transport. A systems understanding of these expression of genes in plants, and biological study of processes will provide the basis for rationale design of this development and other physiological processes. organism in future studies, both in terms of modification beneficial to decreasing the effects of the inhibitors and in Directed Evolution of Metalloenzymes for Organic terms of maximizing solvent production. A systems Synthesis approach of particular interest is constraint-based H. Zhao,* H. Lu modeling of genome-scale metabolic networks that can be National Science Foundation CAREER utilized as a basis for interpreting the outcome of In collaboration with the research group of John Hartwig experiments and as a basis for metabolic engineering. (Chemistry) Relative Expression Analysis for Cancer Diagnosis and Directed evolution has become a proven method for the Prognosis development of enzymes that display non-natural N. D. Price,* J. A. Eddy, S. Gupta, L. B. Edelman, functions. The team is interested in developing J. Dolivo, D. Geman metalloenzyme based selective oxidations for reactions University of Illinois useful in organic synthesis and selective halogenations that The assessment of relative expression reversal patterns provide building blocks for medicinal chemistry. between phenotypes provides a simple, yet powerful Directed Evolution of Novel Homing Endonucleases for approach to aid in the identification of molecular signatures Gene Therapy for disease diagnosis and prognosis. The simplest version H. Zhao,* F. Wen, N. Sun, Y. Nakagawa of this approach is known as top scoring pair analysis, National Institutes of Health; OMT, Inc. which we used to identify a relative expression reversal between two transcripts, OBSCN and PRUNE2, that Gene therapy has the potential to significantly influence separates two very similar-appearing cancers— human health in this millennium and promises new gastrointestinal stromal tumor (GIST) and treatment for a large number of inherited and acquired leiomeiosarcoma (LMS)—that require very different diseases. However, due to the difficulties in achieving treatments (Price et al, PNAS, 2007). We have expanded sustained gene expression and in safe and efficient gene on this idea with the development of a suite of relative delivery, gene therapy has been of limited medical benefit. expression analysis methods, including gene set expression To address these limitations, the proposed research will ordering index (GSEOI), a novel metric for identifying seek to develop a novel technology based on engineered differentially regulated pathways between sets; gene set homing endonucleases that enables correction of diseased expression reversal analysis (GSERA), a new method for genes in mammalian cells, with particular application to comparing sets of high-throughput data based on sickle cell anemia. relationships between a priori defined gene sets (e.g. pathways); relative expression survival analysis (RESA), a method for identifying patterns of marker pairs that aid in cancer prognosis; and relative expression signature

* Denotes principal investigator.

10 Discovery, Design, and Development of Phosphonic This instrument supports nondestructive internal 3-D Acid Antibiotics imaging of samples as thick as 100 µm with 30 nm H. Zhao,* T. Johannes, Z. Shao, C. Denard, N. Nair resolution and will be the first nonsynchrotron based nano- National Institutes of Health CT in the United States. The nano-CT is housed at the Beckman Institute for Advanced Science and Technology In collaboration with research groups of William Metcalf in a shared facility with expert full-time staff and (Microbiology), Wilfred van der Donk and Neil Kelleher equipment to aid with sample prep, acquisition, processing, (Chemistry), and Satish Nair (Biochemistry) analysis, and storage of the nano-CT data. The instrument Phosphonic acids represent a potent, yet underexploited, would complement an already installed National Science group of bioactive compounds with great promise in the Foundation funded micro-CT, filling in the resolution gaps treatment of human diseases. The team is interested in below that instrument’s resolution limit of 5 µm. characterizing and engineering two specific phosphonic Bio-Inspired Active Membranes and Transepidermal acid antibiotics, fosfomycin (an FDA-approved antibiotic) Water and Ion Transport and FR900098 (an antimalarial agent). Both protein J. G. Georgiadis,* C. V. Falkenberg, L. G. Raguin engineering and metabolic engineering approaches are University of Illinois at Urbana-Champaign; National used in combination with a wide variety of biochemical Science Foundation, CTS-0120978; Coordenação de and biophysical methods. Aperfeiçoamento de Pessoal de Nivel Superior (CAPES), Brazil Bioelectric Phenomena Driven by a parallel effort to develop synthetic ion gates and pumps, as well as the study of heat and mass transfer Modeling of Adaptive Filtering Mechanisms in the through human skin, we are developing a model and a Active Electric Sense perm-selective membrane system with extended barrier M. E. Nelson* functionality. The model accounts for the redistribution of National Institute of Mental Health, 1 R01 MH49242 water and active ion transport through a general poroelastic Conducted in the Beckman Institute for Advanced Science medium. The modeling effort is complemented by MRI and Technology experiments. Certain freshwater tropical fish have an active electric Compact MRI-Optical Scanners sense that allows them to detect objects in the environment J. G. Georgiadis,* D. Morris* (Natl. Instit. of Health), based on perturbations in a weak self-generated electric L. G. Raguin field. Electrical signals are detected by specialized University of Illinois at Urbana-Champaign; National receptors on the body surface and analyzed by the brain. Institutes of Health Researchers study the associated neural mechanisms and Recent advances in miniaturization have allowed the computations by constructing biologically detailed design and fabrication of dual modality imaging systems computer models of the early stages of electrosensory combining magnetic resonance imaging (MRI) and processing, including simulations of the self-generated standard systems using visible light. We have designed a electric fields, models of primary afferent response compact MRI scanner based on a permanent magnet and dynamics, multicompartment models of individual millimeter-size radio frequency coils. The bore of the neurons, and neural network models of adaptive filtering scanner allows optical access without degrading MRI in the brain. resolution significantly. The miniature MRI scanner is positioned under the objective of a modified scanning Bioengineering confocal microscope. The setup allows the simultaneous imaging of a submillimeter focal volume by both Acquisition of a Multi-Length Scale Ultra High- instruments. This apparatus is motivated by applications in Resolution X-Ray Nanotomography Instrument the areas of histolopathology and tissue engineering. P. Braun (Mat. Sci. and Engr.),* A. J. Wagoner Johnson,* D. Griffon, W. Hurley, I. Jasiuk National Science Foundation This funding was used to purchase an Xradia ultra-high- resolution x-ray nanotomography instrument (nano-CT).

* Denotes principal investigator.

11 Dynamic Hemodynamic Response and fMRI Signal Cardiovascular and Biomechanical Responses to J. G. Georgiadis,* S. Honecker, L. G. Raguin Firefighting and PPE: Firefighting, PPE, and the Defense Advanced Research Agency; University of Illinois Leading Sources of Firefighter Fatalities and Injuries at Urbana-Champaign G. Horn,* D. Smith,* E. T. Hsiao-Wecksler,* K. S. Rosengren This is a joint experimental and numerical investigation of U.S. Department of Homeland Security the hydrodynamic basis of the BOLD signal during functional MRI scanning of the brain. The first phase Our research project goal is to document cardiovascular involves fabricating an elastomeric perfusion phantom that and biomechanics changes that occur as a result of fire mimics the arterio-venous topology of the visual cortex. fighting activity. We also aim to quantify the extent to The second phase involves the solution of the inverse which enhanced personal protective equipment (PPE) can problem of localizing the injection site of a paramagnetic minimize detrimental changes in cardiovascular and agent in the perfused phentom, which will ultimately biomechanics variables related to the leading causes of line elucidate the connection between the hemodynamic of duty deaths (heart attacks) and injuries (slips, trips, and response and the fMRI BOLD signal. falls). Finally, we will study several novel risk factors to determine their ability to predict an exaggerated Fast, High-Resolution Magnetic Resonance cardiovascular response to firefighting drills. Angiography J. G. Georgiadis,* D. Morris* (Natl. Instit. of Health), Effect of SCBA Bottle Configuration on Gait and L. G. Raguin Balance Performance among Firefighters University of Illinois at Urbana-Champaign; National E. T. Hsiao-Wecksler,* G. Horn, K. Rosengren Institutes of Health [email protected] University of Illinois, Illinois Homeland Security Research This is a comprehensive investigation of Fourier, non- Center Fourier, and q-space magnetic resonance imaging sequences for the quantification of blood perfusion in the As first responders to emergency situations, firefighters microvasculature system. Validation of the new sequences play a crucial role in homeland security. Therefore, is pursued via attendant phantom experiments. providing support to these first responders by examining human factors issues to improve their health and safety is Drug Eluting Scaffolds for Bone Regeneration of critical national importance. Falls and loss of balance on M. Goldwasser,* M. B. Wheeler, the fireground are one of the leading causes of traumatic A. J. Wagoner Johnson,* K. Kim, H. Choi, injuries among firefighters, resulting in ~11K injuries per S. Clark-Deener, F. Bellafiore year (i.e., over 1/4 of all annual fireground injuries). Many Carle University of Illinois at Urbana-Champaign of these events are potentially preventable; however, Translational Research Program Critical Research research examining the underlying mechanisms leading to Initiative these events and efforts to develop intervention programs Bone loss resulting from disease or trauma often requires to prevent falls have been limited. Along with the Illinois a bone graft to restore form and function. The “gold Fire Service Institute (IFSI) at the University of Illinois, standard” for repair is the autograft, which has significant we are developing a research program to explore how disadvantages, including high rates of complication (30%) firefighting equipment and environment affect balance, and significant cost ($2.5 billion/year in the United States). locomotion, and slip, trip, or fall (STF) risk. The The use of an alternative will offer significant economic overarching goal of this program will be to improve savings and will have a major impact on patient quality of firefighter safety by reducing preventable STFs and life. The present study will evaluate the effectiveness of provide knowledge that will aid in the choice and design scaffolds designed to replace autografts. Hydroxyapatite of better firefighting gear. Specifically, we are examining scaffolds containing BMP-2 will be implanted in the pig how the addition of personal protective equipment (PPE), mandible in order to assess the efficacy of drug-eluting which consists of coat, pants, gloves, boots, helmet, hood, scaffolds in bone regeneration. and self-contained breathing apparatus (SCBA), affects STF risk through modification of gait and balance performance.

* Denotes principal investigator.

12 Effect of Tai Chi on Balance and Movement Strategies testbed will culminate with prototypes supplied to health E. T. Hsiao-Wecksler,* K. S. Rosengren care professionals and patients for testing and evaluation. University of Illinois at Urbana-Champaign Gait Analysis of Labrador Retrievers with Cranial Tai Chi has been promoted to older adults as an exercise Cruciate Ligament Deficiency to improve physical and mental fitness. It has also been E. T. Hsiao-Wecksler,* D. J. Griffon,* G. J. Pijanowski found to reduce the likelihood of falling in senior citizens. University of Illinois at Urbana-Champaign; American This project explores how Tai Chi experience may modify Veterinary Medical Association; American Kennel Club postural control mechanisms and movement strategies Cranial cruciate ligament (CCL) rupture is one of the most specifically during unexpected external perturbations to common injuries to the canine hind knee and is the leading balance and while walking over level ground and obstacles. cause of degenerative changes in that joint. Stress injuries We are also investigating new techniques for assessing Tai are believed to result from a combination of conformation Chi skill proficiency. Dynamic systems modeling, control characteristics within the entire limb, resulting in a theory, and movement analysis are used to examine these biomechanical imbalance between forces acting on the issues. We are conducting both cross-sectional studies on cranial tibial thrust. However, the exact role of each of individuals with long-term Tai Chi experience (greater these factors and their significance in relationship with than 2 years) and longitudinal studies on older adults who CCL deficiency has not been defined. The objective of the are receiving Tai Chi training for 5 months. current study is to examine whether there are distinct Fluid Power Assistive Orthoses differences in the kinematics and kinetics of gait in healthy E. T. Hsiao-Wecksler,* A. G. Alleyne, E. Loth and injured Labrador retrievers. To perform the gait [email protected] analysis, we are collecting motion data, which will be National Science Foundation augmented with segment parameter data derived from CT and radiographic images of each animal’s limb. Our long- In the United States alone, there are over 800,000 term goal is to develop a mathematical model integrating individuals affected by gait disabilities caused by a combination of morphometric parameters to estimate the weakness of muscle groups below the knee. This project, risk of developing CCL deficiency in each dog. which is a testbed project for the National Science Foundation funded Engineering Research Center for Multivariate Analysis of Simulated Gait Symmetry Compact and Efficient Fluid Power, will design novel E. T. Hsiao-Wecksler,* J. D. Polk, K. S. Rosengren, ankle foot orthoses (AFOs) with embedded fluid power S. Hong control and actuation that assist a person's functional gait. Applied Life Sciences, University of Illinois at Urbana- Each design iteration will address progressively more Champaign complex gait pathologies, thus allowing for an evolution Acute lower limb injury may lead to chronic gait problems of advanced fluid power concepts, such as power or even disability due to asymmetry between the injured harvesting and fast-response sensing. Initial designs will and uninjured limb. Current clinical gait analysis utilize fluid-controlled (adaptive-passive) systems to techniques used for diagnosis and rehabilitation are correct for toe drop and foot slap, helping to lift the foot qualitative in nature and do not quantitatively assess during swing and initial foot contact during walking. Later recovery. The overall goal of this project is to develop advanced designs will use fluid-powered (active) systems quantitative techniques to assist in the treatment and to provide torque assistance during the propulsive late- monitoring of lower limb injury and asymmetry. Gait is a stance phase of the gait cycle. The testbed will demonstrate dynamic behavior with considerable changes in joint and and integrate compact, efficient, and effective fluid power body positions throughout the gait cycle. We are concepts in a challenging, untethered, human-scale device. developing a novel technique, integrated multivariate gait The long-term goal is to develop and test a series of analysis (IMGA), to distinguish asymmetry in gait and prototype devices that will incorporate current thrust area identify the source of asymmetry. IMGA uses geometric projects, as well as drive new enabling and systems shape analysis (generalized procrustes analysis) with technologies within the center. These technologies will multivariate statistical techniques (principal components follow an evolutionary roadmap addressing the highest analysis and parallel factor analysis) to capture the priority aspects of the overall testbed first, and then dynamic nature of walking behavior that current univariate integrating developments from other center projects as measures cannot capture. they come available over the lifetime of the center. This

* Denotes principal investigator.

13 Optimization-Based Inverse Dynamics to Reduce physiological constraints, limitations, or injuries. Errors in Estimated Joint Torques Specifically, the proposed research will create an E. T. Hsiao-Wecksler* Integrated multivariate motion analysis computational tool University of Illinois at Urbana-Champaign that combines shape-based analysis techniques with multivariate statistical tools; benchmark the statistical Inverse dynamics is a powerful tool for the biomechanical technique against a library of task-specific lower-limb analysis of human movement, and is commonly used to motion patterns; and establish the degree to which the calculate the net torques generated in various limb joints. statistical technique is able to identify the presence and Despite the widespread use of this method, past research degree of constraint in a set of controlled, experimental has shown that the errors in joint torque calculations are data of human ambulation. relatively large. These errors are attributed to inaccuracies in the input variables of the inverse dynamics equations. Tracking Falls and Fall-Related Events throughout the We have determined that the primary contributor is Lifespan inaccuracy in the measured motion (e.g., segment angle E. T. Hsiao-Wecksler,* K. S. Rosengren* profiles), and the secondary contributors include University of Illinois at Urbana-Champaign Initiative on inaccuracies in estimations of body segment parameters Aging (i.e., mass, center of mass location, moment of inertia). To Much of the research related to falls in older adults has used improve the accuracy of inverse dynamics estimations, it retrospective self-reports of falls over the previous 6 is necessary to find techniques to reduce the effects of these months or year. We are developing a prospective slips, error sources. We propose the development of an trips, and falls survey (STAF inventory) to better establish optimization-based approach that can accommodate errors the incident rate of falls and fall-related behaviors. This due to both measured motion and body segment survey evaluates the number of fall-related incidents as parameters. The development of the optimization-based well as the environmental conditions, individual factors, approach will include several studies. The proposed and whether any injuries have occurred over a given study approach has the potential to change the way joint torque period. Falls and fall-related events are being tracked for a estimations are made, and will lead to better clinical and period of 30 days. The STAF inventory is being research tools for the analysis of human movement. administered to college-aged, middle-aged, and older Quantitative Characterization of Complex Motion adults. Patterns Using Shape-Based and Multivariate Variations in Balance and Postural Control throughout Techniques Pregnancy and up to Six Months Postpartum E. T. Hsiao-Wecksler,* H. Dankowicz, S. Hong, E. T. Hsiao-Wecksler* J. D. Polk University of Illinois at Urbana-Champaign National Science Foundation Pregnant women anecdotally state that balance changes as The characterization of complex motion patterns in pregnancy progresses and the circumference of the trunk multisegmented biological organisms is typically achieved and body weight increase. However, no studies have by the identification of normative task-related behaviors examined how balance, and postural control that moderates and the quantitative assessment of deviations from these balance, may vary throughout pregnancy and the normative behaviors. The basic hypothesis of this proposal subsequent postpartum period. This study will assess how is that there are systematic and quantifiable relationships balance and postural control may vary as a consequence of between observed deviations in motion patterns and pregnancy by examining how a subject’s postural sway underlying physiological limitations. Currently available varies over the 9-month pregnancy and a following 6- tools are largely unable to resolve these relationships as month postpartum period. they primarily examine discrete events during a specific task-related motion or are based on univariate statistical Characterization and Modeling of Trabecular Bone techniques. They thus fall short in quantifying I. Jasiuk* spatiotemporally complex motion patterns and in detecting [email protected] interactions across multiple segments and joints. The University of Illinois at Urbana-Champaign fundamental objective of this research effort is to establish We study bone as a hierarchical material and predict its a diagnostic, multivariate, statistical technique for local fields and constitutive responses at different characterizing spatiotemporally complex motion patterns structural scales in healthy and disease states. More and correlating specific motion signatures with

* Denotes principal investigator.

14 specifically, we characterize the hierarchical structure of performance of "snatch" technique. The athlete is modeled normal and osteoporotic bone at several structural levels as a planar 6 degrees of freedom manipulator. The model from nano to macro scales, identify failure and fracture is fixed on one base (toes) and genetic algorithm is used to mechanisms in bone at different structural scales, measure solve the trajectory tracking of the barbell during the lifting in vitro and in vivo bone’s properties at different scales and motion. Generated series of configuration is optimized for develop micromechanics and computational models to minimum total displacement of center of mass (COM) predict local fields and constitutive responses of bone from while preserving maximum stability and minimum total nano to macro scales. consumed energy in each joint. Incorporated in the model are both kinesiological and physiological constraints, Modeling of Bone Adaptation thereby making the model unique and similar to a true I. Jasiuk,* J. A. Dantzig, C. H. Turner (Indiana Univ.) representation of the athlete. University of Illinois at Urbana-Champaign Modeling of Osteonal Cortical Bone Micromechanics We study how bone adapts to mechanical stimuli. Our Fracture modeling is based on the experiments on rat ulna, which M. H. Moeinzadeh,* A. R. Najafi,* A. R. Arshi identified the dependence of bone modeling on the University of Illinois; Amirkabir University of Technology frequency of loading. We use evolution modeling to describe the dependence of the rate of shape change in Microcracks are formed in bone due to fatigue and cyclic cortical bone on the applied mechanical loading and loading. They are associated with loss of bone resistance compare these computational results with the experiments. to fracture. However, the significance of the parameters We analyze this problem computationally using a finite that govern microcrack behavior is not yet fully element software ABAQUS. We obtain finite element understood. The objective of this study is to develop a two- meshes of actual tibia using micro-CT images. The goal of dimensional micromechanical fiber-ceramic matrix this research is to identify important physical parameters composite material model for the osteonal cortical bone. that influence bone remodeling. The solution for the edge dislocations, as a Green's function, is adopted to formulate a system of singular Repair by Regeneration of Large Bone Defects integral equations for the general microcracks in vicinity I. Jasiuk,* N. Fang, J. Cameron of the osteon. The effects of microstructural morphology University of Illinois at Urbana-Champaign and heterogeneity of the bone upon the fracture behavior We study the repair by regeneration of large bone defects is investigated by computing the stress intensity factor near in the adult frog Xenopus laevis limb. Xenopus tadpoles the microcrack tips. have the ability to regenerate limbs but, with age, they lose Mechano-Stimulation and Transduction of Skin Cells this capacity. Thus, in a single animal system we have M. A. Shannon,* S. A. Boppart (Elect. & regeneration capacity and then lack of it. The approach Comput. Engr.), T. E. Euell (Vet. Med.) involves the use of new osteo-inductive bioartificial University of Illinois at Urbana-Champaign scaffolds with optimally designed microstructures for vascularization, cell growth, and mechanical support, in Skin is a mechanically compliant organ that routinely combination with cell transplantation, and chemical undergoes large strains during normal physiological induction to promote regeneration. This research includes function. Several important questions on the 3-D cellular in vitro and in vivo experiments integrated with analytical architecture and intercellular connectivity of the epidermis, and computational modeling. composed primarily of keratinocytes that need answers include: the effect of mechanical strain on the formation, Biomechanics of Weight Lifting: A Stability Analysis maturation, number density, and placement of M. H. Moeinzadeh,* E. Shirzad,* A. R. Arshi desomosomes and hemidesmosomes; the effect of strain [email protected] on the gap junction intercellular communication complex University of Illinois; Amirkabir University of Technology that regulates the equilibrium between keratinocyte growth Most studies on the biomechanics of weight lifting tend to and differentiation; and the effect of local three- concentrate on the injury prevention or performance dimensional topography on the formation of a stratified enhancements via various kinetic or kinematics squamous epithelium during keratinocyte culture on evaluations. An analytical model could prove effective in mechanical compliance. This project utilizes cell culture an individualized approach to performance enhancement. on microfabricated structures to measure the stress and This study simulates the athlete’s motion during the strain within keratinocytes during different stages of

* Denotes principal investigator.

15 development and the formation of mechanical junctions Quantification of the Mechanical Properties of between cells. Hydroxyapatite Scaffolds Containing Multiscale Porosity and BMP-2 using a Swine Mandible Model Aging, Physiological Complexity, Functional A. J. Wagoner Johnson,* M. Goldwasser, M. Wheeler, Limitations, and Disability S. Clark-Deener J. J. Sosnoff,* E. T. Hsiao-Wecksler* Oral Maxillofacial Surgery Foundation Faculty Incentive Grants, University of Illinois at Urbana- Champaign Bone lost to disease or trauma can result in disfigurement and functional impairment. For many, successful repair is The overall goal of our research program is to examine the not possible with current techniques. Furthermore, the longitudinal changes in complexity and its relation to associated costs place an economic burden on affected functional status in older adults. This project seeks to families and the already strained health care system. The establish the validity of utilizing nonlinear dynamical research aims to quantify the mechanical properties of analyses as a tool in identify community dwelling older behavior and bone in growth of the drug-loaded and adults at risk for disability and/or functional limitations. implanted scaffolds, with and without multi-scale porosity Flow in Canaliculi and Lacunae Networks of Bones (MSP). The hypothesis is that MSP increases S. P. Vanka,* I. A. Jasiuk,* D. Marsh osteointegration, which will result in a scaffold construct University of Illinois at Urbana-Champaign with superior mechanical properties and higher likelihood We are making preliminary studies to compute the flow in of success. bone tissue passages consisting of canaliculi and lacunae. A New Approach for Structure-Property in Scaffold The canaliculi are about 100 nm channels feeding Design for Bone Tissue Engineering extravascular flows to lacunae consisting of bone cells. The A. J. Wagoner Johnson* flow in canaliculi can be a combination of continuum and National Science Foundation noncontinuum regimes, and we propose to use a combined The approach here is to focus the scaffold design on the LBM/MD simulation tool to simulate the flow under mechanical properties of the scaffold/tissue composite dynamic loading of the bone. This work is also in rather than on the initial properties. We are constructing a collaboration with Professor Melissa Knothe Tate of Case design space in vitro for different scaffold microstructures Western Reserve University. that represents the range of scaffold/tissue composite Evolution of Bone Formation and the Effects on properties. Bulk hydroxyapatite and composite scaffolds Mechanical Deformation and Damage Mechanisms in containing infiltrated hard and soft polymers, representing Tailorable Scaffolds 100% bone and soft tissue fill, respectively, will be A. J. Wagoner Johnson* fabricated and the mechanical properties determined. A Aircast Foundation subset of microstructures will be implanted in pigs and Bone loss can result in severe disfiguration and loss of evaluated for bone ingrowth and mechanical properties. function. Over 1 million bone graft procedures were Results from the in vivo study will help to make significant reported for 2004, and the associated costs exceed billions advances in understanding structure-property relations in of dollars a year, which places an economic burden on bone tissue engineering scaffolds. families and the health care system. Most bone graft Bioengineering Approaches to Map Stress Propagation procedures use either autograft or allograft, which have in the Cytoskeleton disadvantages. This study examines the role of N. Wang,* S. Na, O. Collin, F. Chowdhury, L. J. Tay, microporosity in osteointegration and the mechanical M. Hong behavior of hydroxyapatite scaffold and scaffold-tissue [email protected] composites. The results will provide a framework for National Institutes of Health, Grant R01 GM072744 assessing the function of an implant, which will guide One of the central questions in cell biology is how clinicians in prescribing rehabilitation strategies for mechanical signals are propagated and distributed inside recovering patients with a range of bone defects. the cytoplasm of living cells. Previously Prof. N. Wang’s lab showed that locally applied stresses were propagated to remote sites in the cytoplasm, a finding that contradicts conventional model predictions. Recently Prof. Wang’s lab demonstrated that force-induced signal transduction

* Denotes principal investigator.

16 (mechanotransduction) is fundamentally different from systems (such as capillary electrophoresis coupled to soluble molecule-induced signal transduction. This matrix-assisted laser desorption/ionization mass important finding is likely to change the direction of spectrometry), and methods that add temporal resolution research of the cell mechanics field since it overturned the for monitoring neurotransmitter release. Currently, these widely held postulate that mechanotransduction is similar approaches are being used to explore the changes in to soluble molecule-induced signal transduction. The work neurons associated with inflammatory pain. has far-reaching implications in an emerging field of mechanomedicine in which mechanics and engineering- Biomaterials based principles and technologies are applied to the diagnosis, treatment, and cure of various human diseases. Controlled Ring-Opening Polymerization J. Cheng,* H. Lu Bioimaging and Neuroimage Analysis University of Illinois Polypeptides are a class of important biomaterials. We Brain Functional Connectivity from fMRI recently developed a group-transfer-ring-opening- Y. M. Wang, J. Xia, J. Marden polymerization (GTROP) method that allows facile University of Illinois Research Board preparation of polypeptides with well-controlled Conducted in the Illini Hall molecular weights and narrow polydispersities. This method may also provide a way for the synthesis of A thorough understanding of the neural mechanisms not peptides with controlled sequence in large quantity, which only requires the accurate delineation of activation regions cannot be readily achieved using existing chemical and (functional segregation or specification) but demands biological methods. precise description of function in terms of the information flow across networks of areas (functional integration). The Cytoplasmic Gene Delivery with Modulated goal of this project is to develop novel statistical methods Copolymer Micelles for robust estimation of functional connectivity or J. Cheng,* R. Tong interactivity by simultaneously examining multiseed University of Illinois correlations via multiple correlation coefficients. Spatially One of the major hurdles in gene delivery is endosomal structured noise in fMRI shall also be taken into account release of delivery vehicles. We are designing block during the identification of functional interconnection copolymer micelle with integrated membrane networks through hypothesis tests. permeability. The membrane permeability can be specifically activated in response to endosomal pH change, Bioinstrumentation resulting in efficient intracellular trafficking and cytoplasmic delivery of nucleic acid therapeutics. The Neurometabolome of a Sensory Neuronal Network Polymer-Drug Nanomedicines for Cancer Therapy J. V. Sweedler,* T. Lapainis, C. Cecala, S. Rubakhin J. Cheng,* R. Tong National Institutes of Health, R01 DE018866 University of Illinois Conducted in the Department of Chemistry It is challenging to make nanoparticles with encapsulated This research involves the development of novel chemotherapeutics or proteins with high loading and microanalytical methodologies to probe metabolites in controlled release profiles. We developed nanoconjugation single cells. As one example, researchers have constructed technology that allows the facile incorporation of various a unique multichannel laser-induced fluorescence therapeutics molecules to degradable polymer detection system that can perform online measurements on nanoparticles at any desirable loading. This technique will zeptomole (10-21 mol) quantities of analyte separated by facilitate the clinical translation of particulate capillary zone electrophoresis. This system increases the nanomedicine in cancer therapy. sensitivity over conventional cellular sampling techniques by several thousandfold. Additionally, researchers have developed and are continuing to investigate new microsampling approaches for analysis of single vesicles, novel multidimensional microseparation-detection

* Denotes principal investigator.

17 Biomineralization and Biomolecular Templates for Nanofabrication BioMEMS and Bionanotechnology G. C. L. Wong,* H. Liang, L. Yang, S. Slimmer, Nano-Therapeutics: Bacterial Mediated Delivery of A. Mishra Nanoparticles into Cells U.S. Department of Energy, Petroleum Research Fund; D. Akin, J. Sturgis, K. Burholder, A. Bhunia, National Science Foundation, Nanoscale Science and J. P. Robinson, R. Bashir* Engineering Center [email protected] In this program, we will use self-assembled biomolecular Purdue University systems as nanoreactors for the formation of inorganic Conducted in the Micro and Nanotechnology Laboratory compounds. The geometric confinement and charge modulation afforded by these self-assembled "templates" In this project, we demonstrate the integration of two allow the synthesis of quantum dots and quantum wires of technologies to develop a simple yet powerful method to controlled sizes, aspect ratios, and crystallographic deliver genes loaded on nanoparticles, which in turn are orientations. carried on the surface of bacteria. Biophysical Approaches to Cystic Fibrosis Therapeutic Electrical Detection of CD4+ Cells from Blood for Strategies Resource Limited Settings (Collaboration with G. C. L. Wong,* L. Sanders, S. Slimmer Harvard University) Beckman Young Investigators Program; Cystic Fibrosis X. Cheng, Y.-S. Liu, D. Irimia, U. Dimirci, Foundation, Cystic Fib Wong 0510 W. Rodriguez, M. Toner, R. Bashir* [email protected] We aim to design new therapeutic technologies for cystic National Institutes of Health fibrosis, CF, based on a fundamental biophysical understanding of the cascade of events that contribute to Conducted in the Micro and Nanotechnology Laboratory respiratory failure. Although CF is a systemic disorder CD4 cell counts measure the health of the immune system affecting a range of epithelial tissues, the major cause of in HIV-infected patients and are essential to diagnose and mortality is lung disease, characterized by persistent monitor HIV-infected patients. The high-end laboratory bacterial infections and the accumulation of viscous equipment used in high-end countries is beyond the reach infected mucus in pulmonary airways. By understanding of third world resource-limited settings. Prof. Toner’s and the structure of interactions of CF mucus, we aim to restore Rodriguez’s groups had developed surfaces functionalized normal immunological function in the airways, as well as with Abs for the specific capture of the target cells. In design a new series of artificial antibiotics. collaboration, Prof. Bashir’s group developed a novel Self-Assembly of Condensed Biomolecular Phases technique for electrical detection of the captured cells that G. C. L. Wong,* T. E. Angelini, J. Butler, R. Coridan, is compatible with large surface area cell capture. O. Rudko, A. Mishra Silicon Field Effect Device Array for Label Free National Science Foundation, DMR 00-71761; U.S. Detection of DNA and Proteins Department of Energy, DE-FG02-91ER45439 O. Elibol, B. Reddy, P. Nair, A. Alam, D. Bergstrom, In cooperation with the Frederick Seitz Materials R. Bashir* Research Laboratory [email protected] National Institutes of Health (NIH); National Science Like-charged polyelectrolytes condense into ordered Foundation (NSF) phases in the presence of multivalent ions. The physical origin of the attractive interaction required for this Conducted in the Micro and Nanotechnology Laboratory condensation has been intensely debated, but no clear In this NIH and NSF funded project, we are working on consensus has emerged. Counterion correlations appear to fabrication, modeling, and selective functionalization of play a key role. In this project, we aim to elucidate the nanoscale thickness field effect transistors for the label free nature of these interactions by mapping out the behavior of detection of micro-RNAs and proteins. Semiconductor multivalent ions on the surfaces of biological based field effect sensing of biomolecules has been shown polyelectrolytes. to be a promising technology for biomedical diagnostics applications.

* Denotes principal investigator.

18 BASIC-Bio-Inspired Assembly of Semiconductor IC motor with micro/nano fabricated devices. The center S. Lee, R. Bashir* overview can be found at (http://www.vet.purdue.edu/ [email protected] PeixuanGuo/NDC/). National Science Foundation Cantilever Based Lab on a Chip for Detection of Conducted in the Micro and Nanotechnology Laboratory Biological Entities K. Park, A. Gupta, J. Jang, D. Akin, S. Broyles, In this work a new process called BASIC (Bio-Inspired M. Ladisch, R. Bashir* Assembly of Semiconductor Integrated Circuits) is [email protected] proposed. The main theme is to use dielectrophoresis and National Institutes of Health (NIH) biochemical molecules for the assembly of useful silicon devices on silicon or other substrate. Conducted in the Micro and Nanotechnology Laboratory Electronic Detection of Spore Germination in Micro- In this NIH funded project, we are developing integrated fluidic Biochips devices with cantilever sensors for detection of viruses. Y.-S. Liu, T. Walter, A. Aronson, R. Bashir* The virus particles we used in the study were vaccinia [email protected] virus, which is a member of the Poxviridae family and National Institutes of Health (NIH); USDA forms the basis of the smallpox vaccine. We have demonstrated the detection of a single vaccinia virus Conducted in the Micro and Nanotechnology Laboratory particle with an average mass of 9.5 fg. In the NIH and USDA funded project, we are developing DNA Nano-Channel Sensors for Single Molecule biochips for the concentration, viability and germination Detection and Characterization detection, and identification of Bacillus anthracis. We M. Venkatesan, D. Peroulis, R. Bashir* have developed a new impedance-based method to detect [email protected] germination of spores in real time within microfluidic NASA/NIH biochips using Bacillus anthracis Sterne spores as the model organism. Conducted in the Micro and Nanotechnology Laboratory Integrated Microfluidic Devices for Detection of In this project we have been working on fabrication of Microorganisms nano-pore channels for the direct characterization of single Y. Liu, S. Bhattacharya, L. Liu, B. Panada, A. Bhunia, molecules of DNA. The nano-pore channels are fabricated M. Ladisch, R. Bashir* in an SOI silicon layer using e-beam lithography and TEM [email protected] beam induced shrinking of the resulting pore. USDA/ARS Center for Food Safety Engineering Conducted in the Micro and Nanotechnology Laboratory Biosensors This USDA funded project through the Center for Food Phospholipid Bilayers at Substrates for Polymer Safety Engineering at Purdue is focused on development Adsorption of technology platforms for the detection and identification S. Granick,* L. Zhang of live bacteria from food and fluid samples. We have U.S. Department of Energy, DE-FG02-02ER 46019 integrated sample preparation, DEP and antibody mediated capture, and capture and culture of bacteria cells inside In cooperation with the Frederick Seitz Materials microfluidic devices. Research Laboratory Nano-Medicine: Use of Phi-29 Packaging RNA A largely unsolved problem in soft materials is to NanoMotor for Active Devices understand how surface reconstruction competes with the J.-M. Moon, D. Akin, C. Mao, P. Guo, R. Bashir* rate of adsorption. Here, we form supported phospholipid [email protected] bilayers and investigate the subsequent adsorption of National Institutes of Health (NIH) charged macromolecules. The stark contrast with well- known views of polymer adsorption onto surfaces whose Conducted in the Micro and Nanotechnology Laboratory structure is “frozen” and unresponsive is relevant not just A specific project recently funded through NIH from biological and biophysical standpoints but also for Nanomedicine Center involves the use of the Phi-29 formulating many cosmetics and pharmaceutical products. packaging RNA nanomotor and interfacing this biological

* Denotes principal investigator.

19 The Materials Science of Phospholipid Bilayers significant challenge for contemporary neurobiology. S. Granick,* A. J. Gewirth,* L. Zhang, V. Feng Researchers are investigating the distribution and release U.S. Department of Energy, DE-FG02-02ER 46019 of neurotransmitters from individual neurons of the marine mollusk Aplysia californica. The application of novel In cooperation with the Frederick Seitz Materials microanalytical methodologies specifically designed for Research Laboratory and the Department of Chemistry these studies allows us to address two questions: Can a Supported lipid bilayers on planar substrates provide neuron target different neuropeptides to specific release model systems to study different physical phenomena on sites? Can a neuron release different neuropeptides at 2-D surfaces with the advantage of a well-defined planar specific terminals under different stimulation paradigms? geometry and, on the practical side, they provide an Using new technologies, more than two hundred new cell- environment in which to study polypeptides and membrane to-cell signaling molecules have been characterized in proteins. In this study we quantify, using AFM (atomic invertebrate model systems. These studies lead to an force microscopy), how the microstructure of a simple improved description of the subcellular dynamics of class of these films evolves during the phase neuronal signaling and contribute to our basic transformation process, from liquid crystalline (fluid) to understanding of the nervous system. solid (gel) phase. Computational Neuroscience Cellular Bioengineering Scale-dependent Processing of Clustered Sensory Neural Repair in the Microcircuit Domain Signals J. V. Sweedler,* R. Nuzzo,* M. Gillette,* L. Millet, M. E. Nelson,* A. S. Feng; N. Ahuja (Elec. & J. Hanson, M. Stewart, M. Zhong Comput. Engr.) W. M. Keck Foundation National Science Foundation, IBN-0422073 Conducted in the Beckman Institute for Advanced Science Conducted in the Beckman Institute for Advanced Science and Technology, Frederick Seitz Materials Research and Technology Laboratory, and Burrill Hall Sensory signals in the real world often arise from signal This project's goal is to develop tools to understand neural sources that are clustered in space and time. Clustered repair and connectivity, and the pathway errors that signals pose both challenges and opportunities for underlie mental retardation, degenerative disease, and biological systems, as well as for intelligent neural neurochemical imbalance-induced depressive illness. By prostheses and machine perception systems. For example, acquiring new insights into local signals that establish an intelligent hearing aid should exhibit robust neuron-neuron interactions, we hope to identify and performance in cluttered environments with other voices implement key effectors of repair to rebuild damaged in the background. This project explores the neural physical agents, determine the effect on the neuron, and mechanisms and computational algorithms that animals finally, to rebuild damaged microcircuits. The project has use to detect, identify, and localize individual signals three phases: fabrication of microdevices and single embedded in an ensemble of similar signals. neuron culture; identification of local signals that selectively alter single synapses; and determination of the essential signaling elements in restoring proper wiring and Control Systems function. Postural Control during Mild Impulsive Perturbations Neurotransmission in Well-Defined Networks E. T. Hsiao-Wecksler* J. V. Sweedler,* S. Rubakhin, N. Hatcher, E. Romanova, University of Illinois at Urbana-Champaign T. Shi, L. Zhang Investigating how individuals respond to disturbances to National Institutes of Health, R01 NS031609 balance is essential to improving our understanding of the Conducted in the Beckman Institute for Advanced Science etiology of falls. Balance and postural control mechanisms and Technology during perturbed stance may change with age. These Understanding the cellular mechanisms that drive differences may manifest themselves in the behavioral neurotransmitter targeting and release represents a very characteristics of the postural response noted immediately after a perturbation. We are particularly interested in the

* Denotes principal investigator.

20 response of the postural control system after a transient current PET and SPECT scanners and in nondestructive perturbation. Limited work has been done to explore evaluation (NDE) in manufacturing, and it will be the basis postural responses to sudden, impulse-like perturbations. for the next generation of diagnostic CT scanners. This will In this investigation, the impulse loading and impulse allow use of CT as a dynamic imaging modality for cardiac response control-theory paradigm will be used to examine imaging, or for real-time surgical guidance in medicine, or the postural response to a mild, quick-release backward as a high-throughput NDE system in manufacturing, or as tug. While impulse response and its associated a high-accuracy security baggage scanner in airports. characteristics are rudimentary concepts in engineering Unfortunately, the high computational cost of current control theory, we have only just begun to extend this cone-beam reconstruction algorithms constitutes a major paradigm to investigate postural control. The purpose of barrier to their applications. We are developing new image this study is to learn more about how to characterize reconstruction techniques that require only computations responses to a transient perturbation, what these responses for an image. These techniques can be 100 times faster than tell us about the postural control system in general, and how current methods for typical images and promise to these responses may vary with age. overcome the computational bottleneck in 3-D cone-beam CT, helping to make it a feasible and commercially viable Digital Signal and Imaging Processing technology for wide use. Fast Algorithms for Tomography Efficient Algorithms for Lossless Data and Image Y. Bresler,* S. Basu, F. Charpentier, J. Brokish, Compression A. George Y. Bresler,* D. Baron National Science Foundation, CCR-9972980 National Science Foundation, CCR-0122293 Conducted in the Coordinated Science Laboratory Conducted in the Coordinated Science Laboratory Computerized Tomography (CT) is the principle In spite of the focus in recent years on lossy compression underlying most of the key diagnostic imaging modalities of audio, images, and video, lossless data compression and many other imaging techniques, including synthetic remains crucial in applications such as text files, aperture radar. We are developing new image facsimiles, software executables, and medical imaging. reconstruction techniques that require only computations Universal source coding algorithms, which deal with for an image, as compared to computations for the current sources whose statistics are unknown, are of particular method of choice, the filtered backprojection (FBP). These importance. The main goal of this research is to develop techniques are orders of magnitude faster than FBP for algorithms featuring fast computation and low memory typical images and promise to overcome the computational use, while providing compression quality near the bottleneck created by new imaging technologies that fundamental theoretical bounds. The resulting algorithms acquire large quantities of data in real time. Similar will have linear complexity and will be better than any developments are pursued for iterative and for 3-D current algorithm with comparable asymptotic reconstruction. compression performance, in terms of computation and/or Minimum-Redundancy Spatiotemporal MRI memory use. Some versions of these algorithms will also Y. Bresler,* Z. P. Liang,* N. Aggarwal have simple structure, admitting fast hardware National Science Foundation, BES-0201876 implementations. A special focus of this research is also on parallel algorithms that allow arbitrary speedup while Conducted in the Coordinated Science Laboratory maintaining the same compression quality. Since its inception in the early 1970s, magnetic resonance Fast Algorithms for 3-D Cone-Beam Tomography imaging (MRI) has become a premier diagnostic imaging Y. Bresler,* J. Brokish, A. George tool. Although its early applications were largely limited [email protected] to stationary objects, MRI has also proven extremely useful National Science Foundation, CCR-0209203 in recent years for dynamic imaging applications, such as cardiac, functional, or interventional imaging. An Conducted in the Coordinated Science Laboratory important challenge confronting dynamic MRI (D-MRI) is In cone-beam tomography, projections are acquired by an to obtain both high spatial and high temporal resolution, area detector, using a source of divergent rays traveling on with three dimensional imaging capability. The goal of this one of several possible trajectories. It is already used in research is to develop, implement, and test rigorously a

* Denotes principal investigator.

21 new unified theoretical framework for minimum- development of a novel graph-theoretic algorithm for redundancy D-MRI data acquisition and image multiscale analysis of MR brain images; further develop, reconstruction. In this framework, dynamic imaging is perfect, and validate a topology-preserving shape treated as a higher-dimensional image reconstruction deformation algorithm so that prior shape information of problem, with time being an independent axis. Instead of brain structures can be incorporated into the image attempting to freeze all motion by sufficiently fast segmentation process effectively; and integrate multiscale acquisition, time variation during acquisition is explicitly analysis with shape deformation for accurate segmentation accounted for in the steps of MRI sequence design, data of brain images and develop a prototype software system acquisition, and image reconstruction. The approach draws to facilitate the application of the developed algorithms for on and extends theories and algorithms introduced by the practical applications in brain mapping. researchers over the past few years and offers the potential Model-Based Tomographic Imaging Methods for significant speedups of the imaging process. Z. P. Liang,* J. Ji, Y. Bresler* Furthermore, combination of the theory and techniques National Institutes of Health, R21 HL62336 developed in this project with fast-scan methods and with methods based on phased-array RF coils will produce Conducted in the Coordinated Science Laboratory combined speedups, greater than any one of the individual The mathematical basis of tomographic imaging is approaches. conventionally rooted in the well-established Fourier or Unwrapping Phase Images radon transform theories, so that image quality is mainly R. Koetter,* D. C. Munson,* Z. P. Liang* dependent on how the data space is sampled. In practice, National Science Foundation, CCR 01-05719 physical and temporal constraints often prevent a sufficient coverage of the data space, resulting in various image Conducted in the Coordinated Science Laboratory artifacts, such as Gibbs ringing, resolution degradation, The primary goal of the project is to develop optimal and various motion effects. This project is aimed at algorithms for the long-standing problem of unwrapping overcoming these problems by developing new model- phase images from various imaging modalities such as based imaging techniques that can incorporate a priori SAR and MRI. Probabilistic inference algorithms will be information into the imaging process effectively. developed and tested using SAR and MRI as testbeds. Prof. Application of these techniques to cardiac imaging and Liang is responsible for phase unwrapping of MRI data. functional brain mapping is also addressed. Brain Image Segmentation by Integrated Multiscale Multisensor Information Fusion Analysis and Shape Deformation Z. P. Liang, H. Pan, K.-Y. Cheng* Z. P. Liang,* S. Wang [email protected] NEC Research Lab; University of Illinois Research Board Defense Advanced Research Projects Agency, MDA972-00-1-0020 Conducted in the Beckman Institute for Advanced Science and Technology Conducted in the Micro and Nanotechnology Laboratory Brain image segmentation is an important and challenging This project is a component of research conducted in the engineering problem confronting brain mapping. By Center for Bio-Optoelectronic Sensor Systems (BOSS). accurately segmenting gray-scale brain images into The primary mission of this center is to develop sensor and various brain structures, we will be able to effectively processing technology for detection of biochemical agents visualize three-dimensional brain structures and carry out in battlefield situations. Prof. Liang is responsible for meaningful neuromorphometric studies. The long-term developing statistical algorithms for multisensor goal of this project is to develop and implement a unified information fusion. processing software platform to effectively support various information processing tasks in neuroimaging or brain mapping. The specific aim of the project is to capitalize on our recent, novel work on graph-based multiscale image analysis and shape deformation to produce an efficient, accurate, and reliable algorithm for identifying brain structures from MR images. We expect to accomplish three specific tasks during the project period: complete the

* Denotes principal investigator.

22 incorporating advances in biomolecular tagging and Energy Systems and recognizing a multiplicity of compounds, making on-chip Thermodynamics analysis of the wide range of biological warfare agents a practical reality. Characterization of Transport and Detection of Toxins in Single Nanopores Experimental Biological and M. A. Shannon,* P. W. Bohn* [email protected] Biomolecular Physics National Science Foundation, Center of Advanced Materials for the Purification of Water with Systems Structural, Functional, and Integration Studies of (WaterCAMPWS) Biocatalysts for Development of Solar Driven, Bio- Hybrid, H -Production Systems The objective is to characterize transport in nanopores by 2 M. Ghirardi* (NREL), K. J. Schulten* studying the properties of isolated single nanofluidic U.S. Department of Energy, NREL XEA-6-55419-01 channels by measuring nanochannel flow and binding characteristics of individual fluorescent probe molecules. In cooperation with the National Renewable Energy A goal is to elucidate mechanisms involved in removal of Laboratory trace contaminates with advanced water purification This research is focused on developing clean and efficient materials. One fundamental problem that pervades all renewable means for hydrogen (H ) production by water purification and reclamation technologies is the 2 understanding of fluid flow and chemical reactions in engineering biocatalysts, integrating them into state-of- restricted geometries that for structures with nanometer the-art photochemical cells, and creating bio-hybrid, characteristic dimensions are fundamentally different than H2-production systems. The project is a collaboration the same phenomena in their larger m-scale counterparts. between experimental and theoretical labs. Therefore, macromolecules may traverse a significant NIRT: Single Molecule Detection in Living Cells using fraction of a nanometer diameter channel while rotating Carbon Nanotube Optical Probes through part of its range, thus significantly changing its M. Strano (Chem. Biomol. Engr.), T. Ha,* K. J. Schulten transport and absorption probabilities. The detection of the National Science Foundation 07-08459 macromolecules within these channels, such as toxins in water, is also a critical need. To do so, we are developing The goal of this project is to investigate and utilize optical a multicompartment, multimembrane biofluidic device transduction mechanisms at the single nanotube level. with characteristic linear dimensions of nanometers and Researchers will develop design rules for macromolecular volumes ranging from tens of attoliters and up, specifically assembly onto carbon nanotubes by calculating designed to manipulate species that must be handled at intermolecular potential functions and simulating optical extremely low masses. Electrical-impedance spectroscopy properties. Kinetic theory and molecular modeling will (EIS) is being investigated for integration into these assist our project in optimizing the strategies for SWNT systems. coating, cellular uptake, and signal enhancement. Theory and modeling will be integrated into the entire DNA Amplification and Detection Chip development effort, providing guidance for selection of M. A. Shannon* biomolecules chosen for coating, explaining the [email protected] mechanism of nanotube internalization and trafficking, and Akonni, Inc. furnishing the quantum mechanical theory for nanotube The objective of this research is to develop a new, rapid optical spectra and their interpretation in terms of method of amplifying DNA using polymerase chain nanotube-adsorbate interactions. reactions (PCR). The PCR chip uses a new micro- nanofluidic device based on the molecular gate, in which multiple types of gates are integrated with PCR reaction chambers to enhance amplification rates, as well as a separation system with electronics and optical systems for detection of completed DNA structures. The device and approach include on-chip heating and cooling,

* Denotes principal investigator.

23 into gelatin microspheres will enhance the bone healing Fluid Dynamics capabilities and augment the natural healing process. Quantitative Visualization of Convective Heat and Embryonic Development in Integrated Microfluidic Mass Transfer in Complex Internal Flows Systems J. G. Georgiadis,* L. G. Raguin M. B. Wheeler,* S. G. Clark, S. Rodriguez-Zas National Science Foundation; National Center for U.S. Department of Agriculture; National Institutes of Supercomputing Applications Health (NIH); Council for Food and Agricultural Research (C-FAR); University of Illinois In applications with complex internal flows, it is the unpredictability of the tortuous fluid particle trajectories The work focuses on identification of embryo viability that produces enhanced heat and mass transfer, beyond the using microfluidics and microelectromechanical systems. level of simple molecular diffusion. The research program The objectives are to develop prototype microscale consists of a combination of noninvasive measurements systems for the handling and evaluation of individual with magnetic resonance imaging (MRI) and numerical embryos and to demonstrate the use of these systems using simulation using Lattice-Boltzmann methods (LBM) of mammalian embryos. The present research is aimed at the such internal flows. Two model systems have been development of technology that will allow study of single considered: a Taylor-Couette reactor and a helical flow cell/embryo biology utilizing integrated embryo transport, mixer driven by a pair of Rushton turbines. culture, and NMR analysis systems. Multi-Factorial Analysis of Porcine Mesenchymal General Engineering: Bioengineering Stem Cells Using High-Speed Robotic Systems M. B. Wheeler,* W. L. Hurley, S. Chaieb, J. Loor, Development of Large Animal Models for Tissue S. G. Clark Engineering Illinois Regenerative Medicine Institute M. B. Wheeler,* S. G. Clark, M. Goldwasser, The use of multi-factorial directed differentiation using A. Wagoner-Johnson high-speed robotic systems, as proposed in this research, University of Illinois; Carle Foundation will enable the examination of large matrices of culture and The lack of large animal models for development and differentiation conditions for stem cells. Studies will testing of scaffolds for hard and soft tissue replacement examine culture conditions in large matrices (i.e. specific limits tissue-engineering research. The objective of this growth factors, differentiation agents) that could not be work is to develop and characterize specific critical size performed manually. Furthermore, our approach enables defects and materials to enable the placement of analysis of genes, known to be involved in the maintenance biomaterial scaffolds into the bone of swine. The surgical of stem cell status or differentiation, from cells cultured techniques accompanying this type of manipulation are under essentially unlimited conditions, as will other cell also being developed. Ultimately this research will provide characteristics that relate to stem cell function in vivo. a robust model to study the replacement of bioengineered Using the automated microscale system in large factorial bone and cartilage. experiments, we will have the capability to establish the foundation for understanding the basic mechanisms Drug-Eluting Scaffolds for Bone Regeneration underlying stem cell development in vitro, and ultimately M. B. Wheeler,* J. S. Bailey, M. Goldwasser, in vivo. A. Wagoner-Johnson, S. G. Clark, H. Choi, K. Kim, F. Bellafiore University of Illinois; Carle Foundation Bone loss, whether from congenital anomalies (e.g. cleft palate), acquired deformities (e.g. resection of tumors, traumatic injuries) or degenerative disease (e.g. osteoporosis, arthritis), often requires reconstructive grafting techniques to restore form and function. The present study will analyze the healing of engineered scaffolds that have been designed to mimic normal bone architecture. The addition of growth factors incorporated

* Denotes principal investigator.

24 MR Imaging of Time-Varying Objects Magnetic Resonance Z. P. Liang,* Y. Bresler,* J. Ji, A. Sen Gupta, A. Guo National Science Foundation, BES 95-02121; National A Cognitive Neuroscience Approach for Enhancing Institutes of Health, NIH-R21-HL062336 Warfighter Training and Performance A. Kramer, M. Fabiani, G. Gratton, W.-T. Fu, B. Sutton, Conducted in the Coordinated Science Laboratory D. Simons Conventional MR imaging techniques have been widely Office of Naval Research; Multidisciplinary University used to obtain high-resolution images from stationary Research Initiative objects. For time-varying objects such as the beating heart, Conducted at the Beckman Institute for Advanced Science however, significant image artifacts often arise that render and Technology the image useless. This project aims to develop a new class of data acquisition and image reconstruction methods for The goal of this project is to examine effective training real-time imaging of cardiac structures and functions. methods and skill transfer in warfighter training. It also seeks to investigate the structural and functional Cognitive Neuroscience of Aging, Culture, and neuroimaging biomarkers of training or of training Cognition potential. The project seeks to develop guidelines for D. C. Park, M. Chee, B. P. Sutton, Y.-Y. Hong effective military training, transfer of skills from training National Institutes of Health; National Institutes of Aging to real-world battlefield situations, and retention of that Conducted at the Beckman Institute for Advanced Science training. and Technology and at the Biomedical Imaging Center Constrained Spectroscopic Imaging The proposed studies are designed to yield benchmark Z. P. Liang,* P. C. Lauterbur* contributions to the study of the neuroscience of culture National Institutes of Health, 1R01CA51430-01A4 and cognition, while simultaneously investigating Conducted in the Beckman Institute for Advanced Science critically important questions about the generality of and Technology neurocognitive aging across cultures. We propose a series of studies that will allow us to assess the interplay between Magnetic resonance spectroscopic imaging promises to experience (through culture) and neurobiology (through provide an entirely new way to examine the dynamics of aging) in sculpting the neurocognitive system. The human biochemical processes in vivo noninvasively. proposed studies also permit a precise evaluation of key However, its practical applications have been limited theories about compensatory neural activations in the because of low sensitivity and long imaging time. The neurocognitive aging process. primary objective of this research is to develop mathematical methods to effectively utilize the readily Neuroimaging of Dedifferentiation and Memory available anatomical information to constrain the spectral Across the Lifespan distribution to reduce imaging time without compromising D. C. Park, B. D. Gonsalves, T. Polk, D. Salat, spatial resolution. B. P. Sutton, Y. M. Wang National Institutes of Health; National Institutes of Aging Functional Brain Imaging Z. P. Liang,* J. Ji Conducted at the Beckman Institute for Advanced Science National Science Foundation, BES 95-02121; Beckman and Technology and the Biomedical Imaging Center Institute for Advanced Science and Technology This work will provide what will be, perhaps, the first Conducted in the Beckman Institute for Advanced Science lifespan characterization of neurocognitive aging, through and Technology an integration of both neuroimaging and behavioral data. We will collect a sample of sufficient size to utilize an The primary objective of this project is to develop new individual differences approach, paying particular signal-processing algorithms for detecting brain activities attention to neural selectivity in ventral visual cortex and from functional MRI data. Researchers are investigating a hippocampal function as predictors of behavioral wavelet-transform-based filtering and t-test method for performance as well as prefrontal activation. signal detection and a multiscale method for image registration and motion correction.

* Denotes principal investigator.

25 Computer Modeling and Magnetic Resonance Imaging signaling transduction in live cells with high tempo-spatial in the Treatment of Speech Disorders in Individuals resolution; and to visualize multiple signaling events Born with Cleft Palate simultaneously in live cells with different fluorescence B. P. Sutton probes and elucidate the molecular hierarchy involved in University of Illinois at Urbana-Champaign Campus cellular signaling transduction. The ultimate goal is to Research Board advance our systematic and insightful understanding of cellular functions leading to physiological and Conducted at the Beckman Institute for Advanced Science pathological consequences. and Technology This project seeks to determine the impact of computer modeling of the oropharyngeal architecture from magnetic Nanoscience resonance images in clinical presurgical planning. National Center for Biomimetic Nanoconductors Specifically, this project used computer visualization and E. Jakobsson,* N. Aluru, H. Bayley, C. J. Brinker, animation to investigate locations of muscle and tissue S. Feller, D. LaVan, A. Parikh, U. Ravaioli, S. Rempe, from pre- and post-surgical MRI scans in cleft palate cases. B. Roux, M. Saraniti, H. L. Scott Developing Novel Methods for Neuroimage Analysis NIH Nanomedicine Roadmap Program with Applications to Cultural Psychology The theme of our center is design of biomimetic Y. M. Wang, D. C. Park, B. P. Sutton nanoconductors and devices utilizing nanoconductors. The Beckman Institute Seed Grant model theoretical systems are native and mutant biological Conducted at the Beckman Institute for Advanced Science channels, ion transport proteins, synthetic channels, and and Technology heterogenous membranes containing channels and Magnetic resonance imaging (MRI) provides an transporters. The model experimental systems are unparalleled opportunity to interrogate both function and engineered protein channels and synthetic channels in structure in the human brain. There is an increasing trend isolation, and in self-assembled membranes supported on to develop large, multisite studies to collect data sets that nanoporous silica scaffolds. The goal is to use biomimetic generalize beyond a single laboratory or geographic area. nanoscale design and engineering of membranes to The techniques for comparing data acquired on different develop therapies. Current active investigators focus on magnets and at different sites by collaborative teams are cystic fibrosis, bacterial and viral infections, and oxidative almost entirely undeveloped. Thus, it is our goal in the damage to membranes. present project to develop more sensitive and improved analysis strategies by considering functional and structural Neural Engineering image analysis of the neuroimaging data acquired at different magnets and sites in an integrated way. Development and Information Processing in 3-D Patterned Neural Circuits Molecular and Cellular Engineering B. C. Wheeler* National Institutes of Health Live Cell Imaging of Signaling Network Conducted in the Beckman Institute for Advanced Science Y. Wang,* M. Ouyang, S. Lu, J. Seong and Technology Translational Biomedical Research Early Career Award, This is a subcontract from Georgia Tech University under Wallace H. Coulter Foundation the group title, "A 3-D Microfluidic/Electronic Neural Conducted in the Beckman Institute for Advanced Science Interface System: In Vitro Studies of Neural Networks, and Technology Plasticity and Injury," sponsored by the National Institutes The objective of this project is to elucidate the molecular of Health Bioengineering Research Partnership Program. mechanism by which cells perceive the external cues and The group proposal is to develop an instrumented three- regulate the intracellular signaling network. Two specific dimensional neural culture system with optical, research interests include the following: to develop microfluidic, electrical, and electronic interfacing so that genetically encoded reporters based on fluorescent experimenters may develop a more sophisticated model of resonance energy transfer (FRET) to visualize and quantify how the brain works. The University of Illinois effort is to extend currently successful two-dimensional patterning

* Denotes principal investigator.

26 technology to three dimensions and to evaluate the predicted increase in the functionality and health of the Optical Imaging neurons. Biophotonics: Optical Coherence Elastography and Engineering Form and Function in Neuronal Networks Biomechanical Modeling of Developing Tissues B. C. Wheeler,* G. J. Brewer (S. Ill. Univ. Med. School) S. A. Boppart,* N. Aluru National Institute of Neural Disorders and Stroke, 1 R01 [email protected] NS052233 National Science Foundation, BES 05-19920 Conducted in the Bioengineering Department and the Conducted in the Beckman Institute for Advanced Science Beckman Institute for Advanced Science and Technology and Technology The immediate goal of this project is to create small As the field of tissue engineering advances, new methods neuronal networks (tens of neurons) that can be designed are needed to develop a more physiological and functional so that their function follows from their geometric form as tissue. This project involves the development a new optical defined by a micrometer chemical pattern. We study diagnostic technique to quantify changing biomechanical correlated input/output functions of extracellularly properties in developing embryos and engineered tissues. stimulated, recorded, and modified action potentials Experimental data will be incorporated into predictive comprising convergent and divergent patterns of activity. computational models to better understand how "form The long-term goal is to design living but artificial neural follows function" and how the biomechanical properties of tissues (a brain on a chip) as a model for fundamental developing tissue contribute to the resulting organization. neuroscience, but with potential application in Ultimately, this will lead to a better understanding of how neuroprosthetics, cell-based biosensors, pharmaceutical external mechanical forces may be used to affect both form screening, and inspiration for computational principles. and function in developing and engineered tissues. Physical Exercise, Mental Activity, and Brain Plasticity CAREER: Functional Optical Coherence Tomography B. C. Wheeler,* W. T. Greenouch* (Phychol.); for Neural Imaging M. B. Wheeler S. A. Boppart,* B. C. Wheeler, W. T. Greenough, National Institutes of Health, PHS 2RO1 AG10154-07 R. Gillette Conducted in the Beckman Institute for Advanced Science [email protected] and Technology National Science Foundation, BES 03-47747 Researchers propose to use morphological and Conducted in the Beckman Institute for Advanced Science morphometric, electrophysiological, and Technology immunocytochemical, and behavioral methods in mature Functional optical coherence tomography (fOCT) is being adult and aging cerebellar cortex to determine which developed to noninvasively track optical changes in neural synapse and neuron types in cerebellar cortex exhibit tissue that occur during electrical activity. In analogy to plasticity in response to learning and to physical exercise; functional MRI, this new technique will permit the analysis which nonneuronal elements exhibit plasticity; the of not only neural structure at high resolutions, but also molecular mechanisms underlying this plasticity; and physiological function at the cellular and molecular level. functional correlates. The use of noninvasive optical techniques can overcome many of the current technical limitations in neurophysiology encountered in the use of single-point micropipette recordings, the use of complex parallel banks of sensitive electronics, or the use of voltage-sensitive dyes that are toxic to cells over extended periods of time.

* Denotes principal investigator.

27 Development of a Multimodality Microscope Optical Coherence Tomography Image-Guided S. A. Boppart,* W. T. Greenough Surgical Resection of Solid Tumors [email protected] S. A. Boppart,* K. Singletary, A. L. Oldenburg National Science Foundation (Major Research [email protected] Instrumentation), BES 06-19257 National Institutes of Health (National Institute of Biomedical Imaging and Bioengineering), 1 R01 Conducted in the Beckman Institute for Advanced Science EB005221 and Technology Conducted in the Beckman Institute for Advanced Science A wealth of structural and functional information can be and Technology obtained from living cells in three-dimensional microenvironments using advanced microscopic Current surgical oncology procedures typically occur at the techniques. This project involves the development of a macro-scale, where a surgeon excises large volumes of novel microscope integrating multiple optical imaging tissue around a tumor in an effort to remove all regions of modalities including optical coherence, multiphoton, and the tumor. Frequently, however, surgical margins are harmonic generation microscopy. The laser sources positive, with microscopic evidence of tumor cells, and the obtained through this Major Research Instrumentation likelihood for residual tumor cells to result in recurrence. grant will enable widely-tunable excitation of exogenous The major goal of this project is to demonstrate and and endogenous fluorophores, as well as ultrabroad validate the use of optical coherence tomography (OCT) bandwidth light for high-resolution optical coherence for high-resolution image-guided surgical resection of microscopy and spectroscopy. This new instrument will solid tumors. With the ability to visualize tissue at the enable simultaneous structural and functional imaging of micrometer (cellular) scale, and in real-time, OCT may cells and tissues, with specific applications in studying alter the paradigm of histological diagnosis by enabling tumor cell biology, optical changes in electrically-active tissue diagnosis to be made intraoperatively, rather than neurons, and the growth of engineered tissues. collecting, processing, and analyzing tissue in the remote pathology laboratory. Magnetomotive Optical Molecular Imaging Probes S. A. Boppart,* K. S. Suslick, K. L. Watkin, A. G. Webb, Optical Coherence Tomography of Breast Cancer: A. L. Oldenburg Feasibility for Tumor Margin Detection and Surgical [email protected] Guidance National Institutes of Health (Roadmap Initiative), 1 R21 S. A. Boppart,* J. G. Kotynek, F. J. Bellafiore, EB005321 P. A. Johnson, K. M. Rowland [email protected] Conducted in the Beckman Institute for Advanced Science Carle Foundation Hospital and Technology Conducted in the Beckman Institute for Advanced Science Molecular imaging involves the use of probes or contrast and Technology and the Carle Foundation Hospital agents targeted to specific molecules such as cell receptors. Virtually every medical and biological imaging modality The major goal is to construct and use a portable optical utilizes some form of contrast agent to enhance the coherence tomography (OCT) system in clinical settings diagnostic utility of the technique. This project involves for the real-time assessment of tissue. The standard of care the development, demonstration, and application of a new typically involves making cell and tissue observations in class of dynamic contrast agent that is responsive to the the pathology laboratory, after collected tissue specimens application of an external, locally-delivered, modulating have been processed, sectioned, stained, and prepared on magnetic field. The magnetomotive effect induced in iron- microscope slides of visualization. This project seeks to oxide nanoparticles produces an optical scattering change this paradigm, by providing real-time, high- signature that is virtually background-free. Molecularly resolution, optical imaging of cells and tissues at the point- targeted magnetic nanoparticles have been shown to of-care. Specifically, our portable OCT system is being provide a unique contrast mechanism for detecting tumor used in the operating rooms at Carle Foundation Hospital cells using optical coherence tomography (OCT). for imaging the surgical margins of resected breast tumor specimens and loco-regional lymph nodes for comparison with corresponding histology, demonstrating feasibility for future intra-operative imaging.

* Denotes principal investigator.

28 Plasmon-Resonant Nanorods as Multifunctional Contrast Agents for Optical Coherence Tomography Optical Physics and Engineering S. A. Boppart, A. Wei* Nanofibrous Scaffolds for Cartilage Engineering [email protected] B. T. Cunningham,* D. Griffon National Institutes of Health, National Cancer Institute, 1 [email protected], [email protected] R01 EB001777 Beckman Institute for Advanced Science and Technology Conducted in the Beckman Institute for Advanced Science Conducted in the Micro and Nanotechnology Laboratory, and Technology the Beckman Institute for Advanced Science and Recent advances in molecular imaging involve the use of Technology, and the College of Veterinary Medicine contrast agents to site-specifically label cells and tissues of The project aims to optimize production of chitosan interest. This project involves the development of novel nanofibers with nanometer-scale diameter for chondrocyte nanoparticle contrast agents that have specific absorption attachment and proliferation. Utilizing nanometer-scale properties detectable with optical coherence tomography. lithography, a silicon template wafer is used to produce Gold particle nanospheres and nanorods will have strong large area rubber molds. By filling the molds with chitosan absorption properties for not only detection, but also for solution, curing the chitosan solution to a solid, and inducing local hyperthermia for the selective destruction harvesting the cured fibers from the mold, large of cancer cells. populations of fibers with any desired diameter can be Targeted Contrast and Therapeutic Agents for produced in large quantities. The fibers produced by this Molecular Biomedical Imaging method will be used to determine the extent to which the S. A. Boppart,* W. D. O'Brien, K. Kim, H. Choi, diameter of chitosan fibers affects in vitro chondrogenesis. M. L. Oelze, K. S. Suslick, J. A. Katzenellenbogen, Our working hypothesis is that decreasing the diameter of M. Strano, D. W. Pack, K. S. Watkin chitosan fibers will improve chondrocytes’ attachment, [email protected] proliferation, and matrix production. Beckman Institute for Advanced Science and Technology Optical Biosensors Conducted across the University of Illinois campus B. T. Cunningham* Recent advances in biomedical imaging have drawn from [email protected] diverse fields to develop multifunctional targeted agents SRU Biosystems that serve to not only generate contrast for detection and Conducted in the Micro and Nanotechnology Laboratory imaging, but also provide a targeted therapeutic approach. An optical biosensor is used to rapidly screen protein-small While many forms of contrast agents exist, and much effort molecule interactions that are not easily screened by other has focused on optimizing contrast enhancement, less is methods. The assay is based upon a sensor technology known about the potential for delivering controlled local called a "photonic crystal" structure that is inexpensively release of drugs or other local therapy, such as manufactured from sheets of plastic film and incorporated hyperthermia or mechanical disruption, from these agents. into disposable microplates. By eliminating the need for a Additionally, our understanding of targeting strategies is label, the assay is less susceptible to errors and artifacts limited, largely due to the complexity of the cellular caused by conformational change or blocking of active biology under normal and disease states. This project binding epitopes. It is envisioned that the technology will assembles an interdisciplinary team of investigators across be used in the context of a primary screen of a chemical campus to focus on these problems, and to develop new library and as a secondary screen for measuring dose- targeted, multifunctional agents. response characteristics of a protein-small molecule combination.

* Denotes principal investigator.

29 Photonic Crystal Biosensor Nanostructures and Integration of Photonic Crystal Sensors with Nanofluid Materials for Advanced Performance Flow Channels B. T. Cunningham* P. Kenis, and B. T. Cunningham* [email protected] [email protected], [email protected] National Science Foundation NSF Center for Nanoscale Chemical-Electrical- Mechanical Manufacturing Systems (NanoCEMMS) Conducted in the Micro and Nanotechnology Laboratory Conducted in the Micro and Nanotechnology Laboratory The specific aims of the research project investigate means and in Roger Adams Laboratory for advancing the state-of-the-art for photonic crystal biosensor performance and applications. Sensor designs The project objective is to incorporate plastic-based will be approached first by computer simulation using photonic crystal optical sensors within nanofluidic flow rigorous coupled wave analysis (RCWA) and finite channels for the detection of biochemical interactions difference time domain (FDTD) methods, followed by between mixed reagents, temperature of reagents, pressure fabrication and testing of the structure. The design goals within sealed reaction vessels, and as a means for will be to produce more narrow resonant spectra, higher indicating the presence or absence of fluid at particular surface/volume ratio, and higher electromagnetic field locations within a fluid network. Using integrated sensors interaction with adsorbed material than first-generation and fluid control within a single small chip, we plan to designs. The incorporation of different materials to demonstrate the ability to simultaneously monitor large increase surface electromagnetic field intensity, and numbers of photonic crystal sensors within the chip using structures to maximize the interaction of the field with a noncontact optical imaging scanner instrument. adsorbed biomolecules, will be demonstrated. Tunable Optical Filters Using Photonic Crystals and Signal and Image Processing Nonlinear Dyes B. T. Cunningham* Practical Compressed Sensing [email protected] M. N. Do,* Y. Bresler Batelle [email protected] National Science Foundation Conducted in the Micro and Nanotechnology Laboratory Conducted in the Coordinated Science Laboratory Photonic crystal narrowband reflectance filters can be designed with resonant wavelengths over the visible A recent breakthrough in mathematics under the name portion of the light spectrum and may have utility as compressed sensing shows that sparse or compressible countermeasures against laser-based systems designed to finite length discrete signals can be recovered from small induce temporary or permanent blindness in pilots. A number of linear, nonadaptive (i.e., universal), and random photonic crystal that would block laser illumination at measurements. This project aims to extend the current specific wavelengths while allowing all other wavelengths methods in compressed sensing to other setups that have to reach the pilot's eyes could be incorporated into the visor overwhelming practical significance. These extensions of a fighter pilot. In addition, a photonic crystal-based visor include constrained acquisition, additional statistical prior might incorporate nonlinear dye material that would on sparse signals, and infinite dimensional cases. The rapidly respond to hostile laser illumination and would specific goals of this project are to: improve signal allow controllable tuning of the filtered wavelength. reconstruction quality; reduce number of measurements required to achieve a specified reconstruction quality; speed up the reconstruction time; and demonstrate these gains on real applications, and in particular in challenging magnetic resonance imaging applications, including functional imaging of the human brain.

* Denotes principal investigator.

30 Resource for Macromolecular Modeling and Theoretical Biological and Bioinformatics Biomolecular Physics K. J. Schulten* National Institutes of Health, PHS 5 P41 RR05969 U.S./U.K. Experiment—Cyberinfrastructure in The Resource develops and maintains computational tools Support of Research that are used by biomedical researchers for simulation and R. Penington,* K. J. Schulten* visualization of biomolecular systems and for remote National Science Foundation, through the National Center collaboration. Moreover, through several collaborations, for Supercomputing Applications the Resource directly serves other research groups by In cooperation with the National Center for providing its scientific and technical expertise. Supercomputing Applications Simulations of Supramolecular Biological Systems The project is a collaboration between the United States K. J. Schulten* and the United Kingdom, and aims at applying GRID University of Illinois computing to biomolecular problems. The U.S. partner will This grant is an umbrella grant providing computer time take advantage of available distributed computational for a wide variety of projects conducted by the Theoretical facilities, both in the United States and in the United and Computational Biophysics Group. All projects employ Kingdom to study various physicochemical properties for large-scale molecular simulations to investigate various a large group of proteins. properties of molecular systems. Mechanisms of Membrane Proteins through In Situ Single Molecule Detection in Living Cells and Tissues Modeling Using a New Class of Optical Sensors Based on Single K. Schulten* Walled Carbon Nanotubes [email protected] M. Strano (Chem. Biomol., Engr.),* K. J. Schulten National Institutes of Health, PHS 1 RO1 GM67887 University of Illinois, Beckman Seed Proposal Membrane proteins function as mediators for exchange of This project investigates the application of carbon material and information across cell membranes as well as nanotubes in designing nanodevices that are of potential converters of electro-osmotic, mechanical, and chemical use in a variety of biological applications. The project is a energy in cells. These proteins are the targets of most combined experimental and theoretical one in which pharmacological interventions and their function is related simulation methodologies are used to design nanotube to many diseases. Often the function of a membrane protein structures and to investigate their interaction with is coupled to the membrane environment through macromolecules such as DNA. The results of the mechanical or electrostatic forces. Advances in simulations will be used to design new molecules, which biomolecular modeling using large parallel computers now will be synthesized and tested by experimental methods. permit the in situ simulation of membrane proteins, the latter requiring, however, simulation volumes of more than Sequencing a DNA Molecule Using a Synthetic 100,000 atoms. Planned research will focus on protein of Nanopore the aquaporin family; the mechanosensitive channel MscL; G. L. Timp,* J-P. Leburton (Elect. & Comput. Engr.); and the chloride channel CIC. A. Aksimentiev, K. J. Schulten, S. Sligar (Biochem.) National Institutes of Health, R01 HG003713 Molecular Mechanisms of Cellular Mechanics K. J. Schulten* In collaboration with Beckman Institute for Advanced National Institutes of Health, R01 GM073655 Science and Technology The focus of this research is on investigating the This project explores the feasibility of sequencing a DNA mechanism of function of various macromolecules in the molecule using a revolutionary type of silicon integrated mechanical function of cells. The project will mainly apply circuit that incorporates a nanopore mechanism with a the method of steered molecular dynamics simulation to molecular trap through a combination of experimental and test and develop hypotheses regarding the structure- theoretical approaches. function relationship of the studied systems that will be Fast and affordable technology for sequencing DNA has tested further by our experimentalist collaborators. the potential to revolutionize medicine by providing a means for accurate diagnostics of about 6,000 genetic and

* Denotes principal investigator.

31 multifactorial diseases, and for tailoring drugs and Development of Methods for Fabricating Uniform treatments to the person's genetic makeup. Micro- and Nanospheres and Capsules of Biodegradable and Biocompatible Materials for Thin Films and Charged Particles Application to Biotechnology K. Kim,* H. Choi,* Y. Choy, C. Kyung, A. Simnick; D. Pack, C. Berkland (Chem. Engr.); Precision Particle Fabrication: The Targeted Delivery R. Jamison (Mat. Sci. & Engr.); of Microsphere Encapsulated Aminobisphosphonates K. Singletary (Food Sci. & Human Nutri.) for Treating Autoimmune and Neoplastic Diseases of [email protected] The Mononuclear Phagocytic System Dong Wha Pharmaceutical; Alkermes T. Fan,* S. Charney,* K. Kim,* H. Choi,* C. Kyung [email protected] Advanced methods of fabricating uniform biodegradable Veterinary Medical Research Funds and biocompatible micro- and nanospheres and multilayer capsules of precise size, shell thickness, porosity, and The main objective of this multidisciplinary initiative is to charge are investigated for various applications in successfully encapsulate two aminobisphosphonates, biotechnology. Applications under investigation include pamidronate and zoledronate, into hydroxyethyl starch advanced drug delivery, tissue engineering, biosensor/ microspheres using a patent-pending technology known as biomarker development, and bioavailability enhancement precision particle fabrication. The long-term goals of this of functional foods. Mechanical, hydrodynamic, electrical, pilot investigation would be to develop a novel, and sol-gel techniques and their combinations are used to commercially viable therapeutic modality for treating fabricate the particles. The smallest particles fabricated to autoimmune and neoplastic disorders involving the date are in the 10-nanometer range, and the largest in the mononuclear phagocytic system. mm range. Tissue Engineered Scaffolds with Imbedded Design of Microparticles for Precision Drug Delivery Microspheres to Improve Bone and Soft Tissue Healing D. Pack,* K. Kim,* H. Choi, C. Berkland, Y. Choy, Through Controlled Delivery of Growth Factors C. Kyung R. Jamison,* K. Kim,* H. Choi,* Y. Choy, A. Morgan, [email protected] A. Sendemir-Urkmez, C. Kearney, C. Kyung National Institutes of Health [email protected] College of Engineering In Collaboration with Chemical and Biomolecular Engineering This research is to optimize the design of tissue engineering substitutes for bone by understanding the relationship The primary goal of this project is to investigate the effects between the size, structure, and distribution of of microparticle size and size distribution, and the shell microspheres in porous scaffolds and their drug release thickness of microcapsules, on small molecule drug characteristics. An array of microspheres from chitosan encapsulation and release. We have developed a novel and hydrogel polymer, biocompatible material currently method for fabrication of uniform polymer microspheres used for treatment of burns and delivery of drugs, will be and microcapsules that allows precise control of the produced, loaded with growth factors, and then embedded particle diameter and shell thickness. By controlling the in porous scaffolds of the same polymers. The rate, particle size, we showed we could achieve zero-order concentration, and duration of drug release will be release of model drugs and discovered several competing measured in vitro for several growth factors that have mechanisms that can affect release rates. Four model drugs shown promise in other studies. that span a range of sizes and water solubility will be investigated: piroxicam, ciprofloxacin, ganciclovir, and cyclosporin.

* Denotes principal investigator.

32 Nam, Y., Brewer, G. J., and Wheeler, B. C. Development Tunneling Microscopy of astroglial cells in patterned neuronal cultures. Journal of Biomaterials Science, Polymer Edition, 18:8, Protein Logic 1091-1100 (Aug. 2007). J. W. Lyding,* S. A. Boppart,* M. Gruebele, G. Timp; N. Aluru* (Indus. & Enter. Syst. Engr.), O'Brien, W. D. Ultrasound-biophysics mechanisms. P. Braun* (Mat. Sci. & Engr.), J. Moore* (Chem.) Progress in Biophysics and Molecular Biology, 93:1-3, National Science Foundation, Nanoscale Interdisciplinary 212-255 (Jan.-Apr. 2007) (http://dx.doi.org/10.1016/ Research Teams j.pbiomolbio.2006.07.010). Conducted in the Beckman Institute for Advanced Science and Technology Oelze, M. L. Bandwidth and resolution enhancement through pulse compression. IEEE Transactions on This program seeks to integrate functional protein arrays Ultrasonics, Ferroelectrics, and Frequency Control, with nanoscale CMOS on silicon. Natural and artificial ion 54:4, 768-781 (Apr. 2007) (http://dx.doi.org/10.1109/ channels are being utilized to interface between biology TUFFC.2007.310). and silicon. Selective chemistry utilizing STM patterning is being used to fabricate the protein templates. Rowe, L., Almasri, M., Lee, K., Fogleman, N., Brewer, G. J., Nam, Y., Wheeler, B. C., Vukasinovic, J., Journal Articles Glezer, A., and Frazier, A. B. Active 3-D microscaffold system with fluid perfusion for culturing in vitro neuronal networks. Lab on a Chip, 4, 475-482 (2007). Bioacoustics Sridhar, M. and Insana, M. F. Ultrasonic measurements Bigelow, T. A., Miller, R. J., Blue, J. P., and of breast viscoelasticity. Medical Physics, 34:12, O'Brien, W. D. Hemorrhage near fetal rat bone exposed 4757-4767 (Dec. 2007). to pulsed ultrasound. Ultrasound in Medicine and Biology, 33:2, 311-317 (Feb. 2007). Sridhar, M., Liu, J., and Insana, M. F. Elasticity imaging of polymeric media. Journal of Biomechanical Church, C. C. and O’Brien, W. D. Evaluation of the Engineering, 129:2, 259-272 (Apr. 2007) (http:// threshold for lung hemorrhage by diagnostic dx.doi.org/10.1115/1.2540804). ultrasound and a proposed new safety index. Ultrasound in Medicine and Biology, 33:5, 810-818 (May Sridhar, M., Liu, J., and Insana, M. F. Viscoelasticity 2007) (http://dx.doi.org/10.1016/j.ultrasmedbio. imaging using ultrasound: Parameters and error 2006.11.006). analysis. Physics in Medicine and Biology, 52:9, 2425-2443 (May 2007) (http://dx.doi.org/ Kim, K. S., Liu, J., and Insana, M. F. Beamforming using 10.1088/0031-9155/52/9/007). spatial matched filtering with annular arrays. Journal of the Acoustical Society of America, 121:4, 1852-1855 Vieira, M., Christensen, B. L., Wheeler, B. C., (Apr. 2007) (http://dx.doi.org/10.1121/1.2642214). Feng, A. S., and Kollmar, R. Survival and stimulation of neurite outgrowth in a serum-free culture of spiral Liu, J., Kim, K. S., and Insana, M. F. SNR comparisons ganglion neurons from adult mice. Hearing Research, of beamforming strategies. IEEE Transactions on 230:1-2, 17-23 (Aug. 2007). Ultrasonics, Ferroelectrics, and Frequency Control, 54:5, 1010-1017 (May 2007) (http://dx.doi.org/10.1109/ Wang, X. M., Galazyuk, A. V., and Feng, A. S. FM signals TUFFC.2007.346). produce robust paradoxical latency shifts in the bat's inferior colliculus. Journal of Comparative Physiology Lyshchik, A., Higashi, T., Asato, R., Tanaka, S., Ito, J., A: Sensory, Neural, and Behavioral Physiology, 193:1, Hiraoka, M., Insana, M. F., Brill, A. B., Saga, T., and 13-20 (Jan. 2007). Togashi, K. Cervical lymph node metastases: Diagnosis at sonoelastography—Initial experience. Radiology, 243:1, 258-267 (Apr. 2007).

* Denotes principal investigator.

33 Yang, S. C. and Feng, A. S. Heterogeneous biophysical Nair, N. and Zhao, H. M. Biochemical characterization properties of frog dorsal medullary nucleus (cochlear of an L-xylulose reductase from Neurospora crassa. nucleus) neurons. Journal of Neurophysiology, 98:4, Applied and Environmental Microbiology, 73:6, 1953-1964 (Oct. 2007). 2001-2004 (Mar. 2007) (http://dx.doi.org/10.1128/AEM. 02515-06). Zemp, R. and Insana, M. F. Imaging with unfocused regions of focused ultrasound beams. Journal of the Pierres, A., Prakasam, A., Touchard, D., Benoliel, A. M., Acoustical Society of America, 121:3, 1491-1498 (Mar. Bongrand, P., and Leckband, D. Dissecting subsecond 2007) (http://dx.doi.org/10.1121/1.2434247). cadherin bound states reveals an efficient way for cells to achieve ultrafast probing of their environment. Biochemical and Biomedical FEBS Letters, 581:9, 1841-1846 (May 2007). Engineering Price, N. D., Trent, J., El-Naggar, A. K., Cogdell, D., Taylor, E., Hunt, K. K., Pollock, R. E., Hood, L., Ang, E. L., Obbard, J. P., and Zhao, H. M. Probing the Shmulevich, I., and Zhang, W. Highly accurate two-gene molecular determinants of aniline dioxygenase classifier for differentiating gastrointestinal stromal substrate specificity by saturation mutagenesis. FEBS tumors and leiomyosarcomas. Proceedings of the Journal, 274:4, 928-939 (Feb. 2007). National Academy of Science of the United States of America, 104, 3414-3419 (2007). Bayas, M. V., Kearney, A., Avramovic, A., van der Merwe, P. A., and Leckband, D. E. Impact of salt Price, N.D. and Shmulevich, I. Biochemical and bridges on the equilibrium binding and adhesion of statistical network models for systems biology. Current human CD2 and CD58. Journal of Biological Chemistry, Opinion in Biotechnology, 18, 365-370 (2007). 282:8, 5589-5596 (Feb. 2007) (http://dx.doi.org/10.1074/ jbc.M607968200). Sullivan, R. and Zhao, H. Cloning, characterization, and mutational analysis of a highly active and stable L- Berkland, C., Pollauf, E., Raman, C., Silverman, R., arabinitol 4-dehydrogenase from Neurospora crassa. Kim, K., and Pack, D. W. Macromolecule release from Applied Microbiology and Biotechnology, 77:4, 845-852 monodisperse PLG microspheres: Control of release (Dec. 2007) (http://dx.doi.org/10.1007/ rates and investigation of release mechanism. Journal s00253-007-1225-0). of Pharmaceutical Sciences, 96:5, 1176-1191 (May 2007). Varde, N. K. and Pack, D. W. Influence of particle size Berkland, C., Pollauf, E., Varde, N., Pack, D. W., and and antacid on release and stability of plasmid DNA Kim, K. Monodisperse liquid-filled biodegradable from uniform PLGA microspheres. Journal of microcapsules. Pharmaceutical Research, 24:5, Controlled Release, 124:3, 172-180 (Dec. 2007) (http:// 1007-1013 (May 2007). dx.doi.org/10.1016/j.jconrel.2007.09.005).

Johannes, T. W., Woodyer, R. D., and Zhao, H. M. Woodyer, R. D., Li, G. Y., Zhao, H. M., and Efficient regeneration of NADPH using an engineered van der Donk, W. A. New insight into the mechanism of phosphite dehydrogenase. Biotechnology and methyl transfer during the biosynthesis of fosfomycin. Bioengineering, 96:1, 18-26 (Jan. 2007). Chemical Communications, 4:4, 359-361 (2007).

Lee, J. K. and Zhao, H. Identification and Wuang, S. C., Neoh, K. G., Kang, E. T., Pack, D. W., characterization of the flavin: NADH reductase (PrnF) and Leckband, D. E. Biomolecules-functionalized PPY- involved in a novel two-component arylamine Fe3O4 nanospheres and their potential for cancer cell oxygenase. Journal of Bacteriology, 189:23, 8556-8563 targeting. Macromolecular Rapid Communications, 28, (Dec. 2007). 816-821 (2007).

Wuang, S. C., Neoh, K. G., Kang, E. T., Pack, D. W., and Leckband, D. E. Polypyrrole nanospheres with magnetic and cell-targeting capabilities. Macromolecular Rapid Communications, 28:7, 816-821 (Apr. 2007) (http://dx.doi.org/10.1002/marc.200600873).

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41 Musick, K. M. and Wheeler, B. C. Three-dimensional Magnetic Resonance microelectrode array for recording dissociated neuronal cultures. 2007 Biomedical Engineering Society Herrington, J. D., Sutton, B. P., and Miller, G. A. Data- Annual Fall Meeting (Los Angeles, CA, Sep. 2007). file formats in neuroimaging: background and tutorial. In Handbook of Psychophysiology, pp. 859-866. Orescanin, M. and Insana, M. F. Ultrasonic radiation (Cacioppo, J. T., Tassinary, L. G., and Berntson, G. G., forces for elasticity imaging of 3-D tissue models. eds.) Cambridge University Press, New York, NY (2007). Medical Imaging 2007: Ultrasonic Imaging and Signal Processing (San Diego, CA, Feb. 2007). Progress in Molecular and Cellular Engineering Biomedical Optics and Imaging: Proceedings of the SPIE, Vol. 6513, 65130 (2007) (http://dx.doi.org/ Botvinick, E. L. and Wang, Y. Laser tweezers in the 10.1117/12.710644). study of mechanobiology in live cells. In Methods in Cell Biology, Volume 82 - Laser Manipulation of Cells and Shah, S. M., Christensen, B. L., Kang, Y.-J, Viera, M., Tissues, pp. 497-523. (Berns, M. W. and Greulich, K. O., Wheeler, B. C., Feng, A. S., and Kollmar, R. Expression eds.) Academic Press, San Diego, CA (2007). of frizzled genes in the inner ear of adult mice. Annual Meeting of the Association for Research in Wang, Y. and Chien, S. Analysis of integrin signaling by Otolaryngology (Denver, CO, Feb. 2007). fluorescence resonance energy transfer. In Methods in Enzymology, Volume 426, pp. 177-201. (Cheresh, D. A., Wheeler, B. C. Engineering form and function in ed.) Elsevier, San Diego, CA (2007). cultured neuronal circuits. 2007 Mediterranean Conference on Medical and Biological Engineering and Papers Presented at Computing (Ljubljana, Slovenia, Jun. 2007). Yapp, R. D., Kalyanam, S., and Insana, M. F. Molecular and structural analysis of viscoelastic properties. Conferences and Medical Imaging 2007: Physiology, Function, and Structure from Medical Images (San Diego, CA, Feb. Symposia 2007). Progress in Biomedical Optics and Imaging: Proceedings of the SPIE, Vol. 6511, 65111 (2007) (http:// Bioacoustics dx.doi.org/10.1117/12.708723).

Dworak, B. J., Scharnweber, R. F., Musick, K. M., Biochemical and Biomedical Khatami, D. B., Brewer, G. J., and Wheeler, B. C. Multi- Engineering compartment neural soma aggregates linked by electrically accessible 3-D axonal microchannels. 2007 Drake, D. M. and Pack, D. W. Active intracellular Biomedical Engineering Society Annual Fall Meeting (Los transport of polyethylenimine/DNA polyplexes. 2007 Angeles, CA, Sep. 2007). American Institute of Chemical Engineers Annual Meeting (Salt Lake City, UT, Nov. 2007). Khatami, D. B., Dworak, B. J., Brewer, G. J., and Wheeler, B. C. Functional connectivity analysis and Drake, D. M. and Pack, D. W. Biochemical investigation tracking in biological neuronal networks patterned on of intracellular transport of polyethylenimine/DNA microelectrode arrays. 2007 Biomedical Engineering polyplexes. 2007 Controlled Release Society Annual Society Annual Fall Meeting (Los Angeles, CA, Sep. Meeting (San Diego, CA, Jul. 2007). 2007). Ford, A. N. and Braatz, R. D. Modeling autocatalytic Kollmar, R., Vieira, M., Christensen, B. L., Shah, S. M., controlled-release drug delivery from PLGA Kang, Y.-J., Wheeler, B. C., and Feng, A. S. Promoting microspheres. 2007 American Institute of Chemical neurite outgrowth from adult spiral ganglion neuron. Engineers Annual Meeting (Salt Lake City, UT, Nov. Age Related Hearing Impairment Congress 2007 2007). (Antwerp, Belgium, May 2007).

42 Kishida, M., Ford, A. N., Pack, D. W., and Braatz, R. D. Varde, N. K. and Pack, D. W. Encapsulation and release Optimal control of cellular uptake rate in tissue of plasmid DNA from uniform PLGA microspheres. scaffolds. 2007 American Institute of Chemical Engineers 2007 Controlled Release Society Annual Meeting (San Annual Meeting (Salt Lake City, UT, Nov. 2007). Diego, CA, Jul. 2007).

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Leckband, D. E. Chemistry of bioadhesion: Supported Hsiao-Wecksler, E. T. and Hur, P. Sway response and membranes and membrane arrays for biosensing relative stability of the postural control system to an applications. Pittcon (Chicago, IL, Feb. 2007). impulsive perturbation. 44th Annual Society of Engineering Science Conference (College Station, TX, Leckband, D. E. Making sticky surfaces: The chemistry Oct. 2007). of biological adhesion. Buergenstock Conference on Stereochemistry (Buergenstock, Switzerland, Apr. 2007). Hur, P., Duiser, B. A., and Hsiao-Wecksler, E. T. Exploring the impulse response of the postural control Leckband, D. E. Microfluidic patterning for system. 31st Annual Meeting of the American Society of investigations of cell migration and adhesion. Gordon Biomechanics (Stanford, CA, Aug. 2007). Research Conferences on Thin Organic Films (Aussois, France, May 2007). Hur, P., Naito, S., and Hsiao-Wecksler, E. T. Estimating lean angle through application of the gravity line Leckband, D. E. Nanomechanics of bioadhesion: From projection algorithm. 31st Annual Meeting of the single molecules to tissues. BIOSURF VII (Zurich, American Society of Biomechanics (Stanford, CA, Aug. Switzerland, Aug. 2007). 2007).

Leckband, D. E. Selective protein adsorption vs cell Jang, J. and Hsiao-Wecksler, E. T. Repeated quiet-stance behavior on surfaces. Graduate Program in Areas of stabilometric balance testing over a 15-month period. Basic and Applied Biology (Porto, Portugal, May 2007). 18th Annual Meeting of the International Society of Posture and Gait Research (Burlington, VT, Jul. 2007). Pack, D. W. (Re)engineering of gene delivery vectors. International Conference on Materials for Advanced Jang, J., Hsiao, K. T., and Hsiao-Wecksler, E. T. Technologies (Singapore, Jul. 2007). Increasing stance width compensates for perceived degradation in balance during pregnancy. 18th Annual Pack, D. W. Hybrid viral/synthetic gene delivery Meeting of the International Society of Posture and Gait nanovectors: Toward an artificial virus. Center for Research (Burlington, VT, Jul. 2007). Nanoscale Science and Technology Nanotechnology Workshop (Urbana, IL, May 2007). Jasiuk, I. Trabecular bone as a complex system. Understanding Complex Systems Conference (Urbana, IL, Pack, D. W. Overcoming delivery challenges in gene May 2007). therapy. 2007 Drug Delivery Conference (San Diego, CA, Jun 2007). Javadi, A. H., Arshi, A. R., Shirzad, E., and Moeinzadeh, M. H. A genetic algorithm approach to Pack, D. W. Precision particle fabrication for singularity avoidance in the analysis of weight lifting controlled-release drug delivery. Design of Medical performance. 31st Annual Meeting of the American Devices Conference (Minneapolis, MN, May 2007). Society of Biomechanics (Stanford, CA, Aug. 2007). Proceedings of the 31st Annual Meeting of the American Society of Biomechanics (2007) (http:// www.stanford.edu/group/asb2007/call.html).

43 Karampinos, D. C., King, K. F., and Georgiadis, J. G. Riemer, R. and Hsiao-Wecksler, E. T. Reducing errors Direction-sensitive perfusion with Q-space MRI: in inverse dynamics–based joint torques through Phantom validation and in-vivo calf muscle probing. optimized body segment parameters and segment International Society for Magnetic Resonance in Medicine, motion profiles. 31st Annual Meeting of the American 15th Scientific Meeting and Exhibition (Berlin, Germany, Society of Biomechanics (Stanford, CA, Aug. 2007). May 2007). Shorter, K. A., Polk, J. D., Rosengren, K. S., and Kumar, N., Jasiuk, I., and Dantzig, J. A. Mathematical Hsiao-Wecksler, E. T. Detecting asymmetries in braced modeling of bone adaptation. 44th Annual Society of and unbraced limbs. 31st Annual Meeting of the Engineering Science Annual Conference (College Station, American Society of Biomechanics (Stanford, CA, Aug. TX, Oct. 2007). 2007).

Major, M. J., Beaudoin, A., Kurath, P., and Shorter, K. A., Polk, J. D., Rosengren, K. S., and Hsiao-Wecksler, E. T. Biomechanical study of Hsiao-Wecksler, E. T. A new method for assessing gait aggressive in-line skating. 1st International Conference symmetry. 18th Annual Meeting of the International on Mathematical Modelling in Sport by the Institute of Society of Posture and Gait Research (Burlington, VT, Jul. Mathematics and Its Applications (Manchester, UK, Jun. 2007). 2007). Proceedings of the 1st International Conference on Mathematical Modelling in Sport by the Institute of Stoitsis, J., Bastouni, E., Karampinos, D. C., Mathematics and Its Applications, Vol. 25(12), 1411-1422 Bosshard, J. C., Lu, J., Golemati, S., Wright, S. M., (2007). Georgiadis, J. G., and Nikita, K. S. Velocity extraction from spin-tagging MRI images using a weighted least- Mintz, E., Harris, W., Bota, K., Mehrabi, S., Moeti, L., squares optical flow method. 2007 Institute of Electrical Chandrasekharan, R., and Shannon, M. A. Preparation and Electronics Engineers International Workshop on of TiO2/Al2O3 and N-doped TiO2/Al2O3 composites, Imaging Systems and Techniques (Krakow, Poland, Mar. and applications to photodeactivation of bacteria and 2007). viruses. 233rd American Chemical Society National Meeting (Chicago, IL, Mar. 2007). Sutton, B. P., Ouyang, C., Karampinos, D. C., Georgiadis, J. G., and Ciobanu, L. Flow enhancement of Monty, C., Oh, I., Masel, R. I., and Shannon, M. A. signal intensity (FENSI): Validation of localized flow Microfabricated acetylcholinesterase-based measurements. International Society for Magnetic electrochemical biosensors for detection of Resonance in Medicine, 15th Scientific Meeting and organophosphorus nerve agents. 211th Meeting of the Exhibition (Berlin, Germany, May 2007). Electrochemical Society (Chicago, IL, May 2007). Computational Biology Naito, S., Obinata, G., Hase, K., and Hsiao-Wecksler, E. T. Effect of dual task on the Chen, C.-C., Zhu, X., and Zhong, S. Selection of postural control system. 28th Conference of the Society thermodynamic models for combinatorial control of of Biomechanisms, Japan (Gifu, Japan, Nov. 2007). multiple transcription factors in early differentiation of embryonic stem cells. International Conference on Raeisi Najafi, A., Arshi, A. R., Eslami, M. R., Bioinformatics and Computational Biology (Las Vegas, Katoozian, H. R., Moeinzadeh, M. H., and Mallakin, E. NV, Jun. 2007). The effect of bone microstructure on microcracks propagation trajectory. 31st Annual Meeting of the American Society of Biomechanics (Stanford, CA, Aug. 2007). Proceedings of the 31st Annual Meeting of the American Society of Biomechanics (2007).

Riemer, R. and Hsiao-Wecksler, E. T. Optimization- based inverse dynamics to reduce the effect of motion errors in joint torque calculations. 44th Annual Society of Engineering Science Conference (College Station, TX, Oct. 2007).

44 Haldar, J. P., Hernando, D., Budde, M. D., Wang, Q., Digital Signal and Imaging Processing Song, S., and Liang, Z. High-resolution MR metabolic imaging. 29th Annual International Conference of Bresler, Y., Aggarwal, N., and Sharif, B. Patient-adaptive Institute of Electrical and Electronics Engineers spatio-temporal MRI: From PARADIGM to Engineering in Medicine and Biology Society (Lyon, PARADISE and beyond. 4th Institute of Electrical and France, Aug. 2007). Proceedings of the 29th Annual Electronics Engineers International Symposium on International Conference of Institute of Electrical and Biomedical Imaging: Macro to Nano (Arlington, VA, Apr. Electronics Engineers Engineering in Medicine and 2007). Proceedings of the 4th Institute of Electrical and Biology Society 4324-4326 (2007) (http://dx.doi.org/ Electronics Engineers International Symposium on 10.1109/IEMBS.2007.4353293). Biomedical Imaging: Macro to Nano 980-983 (2007). Liang, Z. Spatiotemporal imaging with partially Brokish, J. and Bresler, Y. Sampling requirements for separable functions. 4th Institute of Electrical and circular cone beam tomography. 2006 Institute of Electronics Engineers International Symposium on Electrical and Electronics Engineers Nuclear Science Biomedical Imaging: Macro to Nano (Arlington, VA, Apr. Symposium Conference (San Diego, CA, Nov. 2006). 2007). Proceedings of the 4th Institute of Electrical and 2006 Institute of Electrical and Electronics Engineers Electronics Engineers International Symposium on Nuclear Science Symposium Conference Record (2007). Biomedical Imaging: Macro to Nano 988-991 (2007) (http://dx.doi.org/10.1109/ISBI.2007.357020). George, A. K. and Bresler, Y. A fast shear-like divergent- beam backprojection algorithm. 2006 Institute of Sharif, B. and Bresler, Y. Adaptive real-time cardiac Electrical and Electronics Engineers Nuclear Science MRI using PARADISE: Validation by the Symposium (San Diego, CA, Nov. 2006). 2006 Institute of physiologically improved NCAT phantom. 4th Institute Electrical and Electronics Engineers Nuclear Science of Electrical and Electronics Engineers International Symposium Conference Record (2007). Symposium on Biomedical Imaging: Macro to Nano (Arlington, VA, Apr. 2007). Proceedings of the 4th Haldar, J. P. and Liang, Z. High-resolution diffusion Institute of Electrical and Electronics Engineers MRI. 29th Annual International Conference of Institute International Symposium on Biomedical Imaging: Macro of Electrical and Electronics Engineers Engineering in to Nano 1020-1023 (2007). Medicine and Biology Society (Lyon, France, Aug. 2007). Proceedings of the 29th Annual International Conference Sharif, B. and Bresler, Y. Affine-corrected PARADISE: of Institute of Electrical and Electronics Engineers Free-breathing patient-adaptive cardiac MRI with Engineering in Medicine and Biology Society 311-314 sensitivity encoding. 4th Institute of Electrical and (2007) (http://dx.doi.org/10.1109/IEMBS.2007.4352286). Electronics Engineers International Symposium on Biomedical Imaging: Macro to Nano (Arlington, VA, Apr. Haldar, J. P., Hernando, D., and Liang, Z. Shaping spatial 2007). Proceedings of the 4th Institute of Electrical and response functions for optimal estimation of Electronics Engineers International Symposium on compartmental signals from limited Fourier data. 4th Biomedical Imaging: Macro to Nano 1076-1079 (2007) Institute of Electrical and Electronics Engineers (http://dx.doi.org/10.1109/ISBI.2007.357042). International Symposium on Biomedical Imaging: Macro to Nano (Arlington, VA, Apr. 2007). Proceedings of the 4th Institute of Electrical and Electronics Engineers Engineering Education International Symposium on Biomedical Imaging: Macro to Nano 1364-1367 (2007) (http://dx.doi.org/10.1109/ Alley, M., Srajek, L., Wagoner Johnson, A. J., and ISBI.2007.357114). Stickler, M. Evaluation of two workshops for graduate students on communicating research in engineering and science. 37th American Society for Engineering Education/Institute of Electrical and Electronics Engineers Frontiers in Education Conference (Milwaukee, WI, Oct. 2007).

45 Stone, S. S., Yi, H., Hwu, W. W., Haldar, J. P., Magnetic Resonance Sutton, B. P., and Liang, Z. P. How GPUs can improve the quality of magnetic resonance imaging. 1st Haldar, J. P., Hernando, D., Sutton, B. P., and Workshop on General Purpose Processing on Graphics Liang, Z. P. Non-Fourier measurement ensembles for Processing Units (Boston, MA, Oct. 2007). compressed sensing in MRI. International Society for Magnetic Resonance in Medicine 16th Annual Meeting Wang, Y. M. and Xia, J. Functional interactivity in fMRI (Berlin, Germany, May 2007). Proceedings of the using multiple seeds' correlation analyses—Novel International Society for Magnetic Resonance in Medicine methods and comparisons. 20th International 16th Annual Meeting (2007). Conference on Information Processing in Medical Imaging (Kerkrade, the Netherlands, Jul. 2007). Proceedings, Hernando, D., Haldar, J., Sutton, B., and Liang, Z. Lecture Notes in Computer Science 147-159 (2007). Removal of lipid signal in MRSI using spatial-spectral constraints. 4th Institute of Electrical and Electronics Wang, Y. M., Xia, J., and Marden, J. Multiple correlation Engineers International Symposium on Biomedical and multi-seed for robust inference of functional Imaging: From Nano to Macro (Arlington, VA, Apr. 2007). connectivity in fMRI. 4th Institute of Electrical and Proceedings of the 4th Institute of Electrical and Electronics Engineers International Symposium on Electronics Engineers International Symposium on Biomedical Imaging: From Nano to Macro (Arlington, Biomedical Imaging: From Nano to Macro 1360-1363 VA, Apr. 2007). Proceedings of the 4th Institute of (2007) (http://dx.doi.org/10.1109/ISBI.2007.357113). Electrical and Electronics Engineers International Symposium on Biomedical Imaging: From Nano to Macro Jacob, M. and Sutton, B. P. Non-iterative decomposition 408-411 (2007). of fat and water using chemical shift. International Society for Magnetic Resonance in Medicine 16th Annual Zhou, C., Park, D. C., Styner, M., and Wang, Y. M. ROI Meeting (Berlin, Germany, May 2007). Proceedings of the constrained statistical surface morphometry. 4th International Society for Magnetic Resonance in Medicine Institute of Electrical and Electronics Engineers 16th Annual Meeting (2007). International Symposium on Biomedical Imaging: From Nano to Macro (Arlington, VA, Apr. 2007). Proceedings Jacob, M. and Sutton, B. P. Non-iterative Dixon of the 4th Institute of Electrical and Electronics Engineers decomposition of fat and water. 4th Institute of Electrical International Symposium on Biomedical Imaging: From and Electronics Engineers International Symposium on Nano to Macro 1212-1215 (2007). Biomedical Imaging: From Nano to Macro (Arlington, VA, Apr. 2007). Proceedings of the 4th Institute of Electrical and Electronics Engineers International Molecular and Cellular Engineering Symposium on Biomedical Imaging: From Nano to Macro 1356-1359 (2007) (http://dx.doi.org/10.1109/ISBI. Na, S., Wang, Y., and Wang, N. Rapid signal 2007.357112). transduction in the cytoplasm induced by local mechanical stresses. American Society of Cell Biology Karampinos, D. C., King, K. F., Sutton, B. P., and 47th Annual Meeting (Washington, DC, Dec. 2007). Georgiadis, J. G. In vivo study of cross-sectional skeletal muscle fiber asymmetry with diffusion-weighted MRI. Ouyang, M., Xu, J., Weiss, S. J., Giepmans, B. N., and 29th Annual International Conference of the Institute of Wang, Y. Polarized MT1-MMP activity in live cells Electrical and Electronics Engineers Engineering in visualized by a FRET biosensor. 2007 Biomedical Medicine and Biology Society (Lyon, France, Aug. 2007). Engineering Society Annual Fall Meeting (Los Angeles, Proceedings of the 29th Annual International Conference CA, Sep. 2007). of the Institute of Electrical and Electronics Engineers Engineering in Medicine and Biology Society 327-330 Ouyang, M., Xu, J., Weiss, S. J., Giepmans, B. N., and (2007) (http://dx.doi.org/10.1109/IEMBS.2007.4352290). Wang, Y. Polarized MT1-MMP activity in live cells visualized by a FRET biosensor. 5th Annual Biophysics Malandraki, G. A., Perlman, A. L., and Sutton, B. Neural and Computational Biology Symposium (Urbana, IL, Nov. activation of swallowing using fMRI in young adults. 2007). American Speech-Language-Hearing Association Annual Convention (Boston, MA, Nov. 2007).

46 Seong, J., Joo, C., Ha, T., and Wang, Y. Live-cell imaging Bhargava, R., Keith, F. N., Srinivasan, G., Reddy, R. K., of Src activation by FRET in neuronal growth cone. and Kong, R. Practical aspects of automated 37th Annual Meeting of the Society for Neuroscience (San histopathology using FTIR imaging. 33rd Federation of Diego, CA, Nov. 2007). Analytical Chemistry and Spectroscopy Societies Annual Conference (Memphis, TN, Oct. 2007). Seong, J., Joo, C., Ha, T., and Wang, Y. Live-cell imaging of Src activation by FRET in neuronal growth cone. Bhargava, R., Reddy, R. K., and Llora, X. Histopathology 5th Annual Biophysics and Computational Biology without human supervision. 2007 Biomedical Symposium (Urbana, IL, Nov. 2007). Engineering Society Annual Fall Meeting (Los Angeles, CA, Sep. 2007). Seong, J., Lu, S., and Wang, Y. Differential Src activities at subcompartments of the plasma membrane. 2007 Bhargava, R., Srinivasan, G., Reddy, R., Llora, X., and Biomedical Engineering Society Annual Fall Meeting (Los Kong, R. FTIR spectroscopic imaging for cancer Angeles, CA, Sep. 2007). pathology. 2007 Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy (Chicago, IL, Feb. Xu, J., Dong, R., Nuzzo, R., and Wang, Y. 2007). Microenvironment effects on cellular functions visualized by FRET biosensors. 2007 Biomedical Crecea, V., Oldenburg, A. L., Ralston, T. S., and Engineering Society Annual Fall Meeting (Los Angeles, Boppart, S. A. Phase-resolved spectral-domain CA, Sep. 2007). magnetomotive optical coherence tomography. Coherence Domain Optical Methods and Optical Nanoscience Coherence Tomography in Biomedicine XI (San Jose, CA, Jan. 2007). Progress in Biomedical Optics and Imaging: Proceedings of the SPIE, Vol. 6429, 64291 (2007) (http:// Tilson, J. L., Rendon, G., Ger, M.-F, and Jakobsson, E. dx.doi.org/10.1117/12.702649). MotifNetwork: A grid-enabled workflow for high- throughput domain analysis of biological sequences: Keith, F. N. and Bhargava, R. Automated breast tissue Implications for annotation and study of phylogeny, histopathology using mid-IR spectroscopic imaging. protein interactions, and intraspecies variation. 7th 34th Federation of Analytical Chemistry and Spectroscopy Institute of Electrical and Electronics Engineers Societies Annual Conference (Memphis, TN, Oct. 2007). International Conference on Bioinformatics and Bioengineering (Boston, MA, Oct. 2007). Proceedings of Kodali, A. K. and Bhargava, R. Modeling scattering in the 7th Institute of Electrical and Electronics Engineers vibrational spectroscopy and imaging. 34th Federation International Conference on Bioinformatics and of Analytical Chemistry and Spectroscopy Societies Bioengineering 620-627 (2007). Annual Conference (Memphis, TN, Oct. 2007). Optical Imaging Levin, I. W. and Bhargava, R. Fourier-transform infrared histopathologic imaging: A practical protocol. Bhargava, R., Keith, F. N., Srinivasan, G., Reddy, R. K., 4th International Conference on Advanced Vibrational and Kong, R. FTIR imaging for pathology. 2007 Eastern Spectroscopy (Corfu, Greece, Jun. 2007). Analytical Symposium (Somerset, NJ, Nov. 2007). Llora, X., Reddy, R., Matesic, B., and Bhargava, R. Bhargava, R., Keith, F. N., Srinivasan, G., Reddy, R. K., Towards better than human capability in diagnosing and Kong, R. Mid-infrared spectroscopic imaging for prostate cancer using infrared spectroscopic imaging. automated cancer pathology. Engineering Conferences 9th Annual Genetic and Evolutionary Computation International : Advances in Optics for Biotechnology, Conference (London, UK, Jul. 2007). Proceedings of the Medicine and Surgery (Naples, FL, Jun. 2007). 9th Annual Genetic and Evolutionary Computation Conference 2098-2105 (2007) (http://dx.doi.org/ 10.1145/1276958.1277366).

47 Marks, D. L., Ralston, T. S., Carney, P. S., and Boppart, S. A. High numerical aperture fall-field Energy Systems and optical coherence tomography with space-invariant Thermodynamics resolution without scanning the focus. Coherence Domain Optical Methods and Optical Coherence Shannon, M. A., Kuo, T., Sweedler, J. V., and Bohn, P. W. Tomography in Biomedicine XI (San Jose, CA, Jan. 2007). Hybrid Microfluidic and Nanofluidic System [Utility Progress in Biomedical Optics and Imaging: Proceedings Patent Grant], # US 7220345, May 2007. of the SPIE, Vol. 6429, 64291 (2007) (http://dx.doi.org/ 10.1117/12.703372). Optical Imaging Oldenburg, A. L., Hansen, M. N., Wei, A., and Boppart, S. A. Backscattering albedo contrast in OCT Boppart, S. A., Toublan, F. J., Marks, D. L., and Suslick, using plasmon-resonant gold nanorods. Coherence K. S. Optical Contrast Agents for Optically Modifying Domain Optical Methods and Optical Coherence Incident Radiation [Utility Patent Grant], # US Tomography in Biomedicine XI (San Jose, CA, Jan. 2007). 7198777, Apr. 2007. Progress in Biomedical Optics and Imaging: Proceedings of the SPIE, Vol. 6429, 64291 (2007) (http://dx.doi.org/ 10.1117/12.702847). Awards and Honors

Ralston, T. S., Marks, D. L., Carney, P. S., and Narayan R. Aluru Boppart, S. A. Real-time inverse scattering for optical Faculty Early Career Development Program (CAREER) coherence tomography. Biomedical Applications of Award, National Science Foundation, 1999 Light Scattering (San Jose, CA, Jan. 2007). Progress in Faculty Fellowship, National Center for Supercomputing Biomedical Optics and Imaging: Proceedings of the SPIE, Applications, 1999 Vol. 6446, 644608 (2007) (http://dx.doi.org/ Distinguished Young Author Award, Center for Middle 10.1117/12.699285). Eastern Studies, 2001 Xerox Award for Faculty Research, University of Illinois Srinivasan, G., Yapp, R. D., Insana, M. F., and College of Engineering, 2001 Bhargava, R. Characterization of gelatin by FTIR Willett Faculty Scholar Award, University of Illinois spectroscopy and imaging. 2007 Pittsburgh Conference College of Engineering, 2002-2005 on Analytical Chemistry and Applied Spectroscopy Faculty Fellow, National Center for Supercomputing (Chicago, IL, Feb. 2007). Applications, 2006 Gustus L. Larson Memorial Award, American Society of Zysk, A. M., Adie, S. G., Armstrong, J. J., Leigh, M. S., Mechanical Engineers, 2006 Paduch, A., Nguyen, F. T., Sampson, D. D., and R. H. Gallagher Young Investigator Award, U.S. Boppart, S. A. Needle-probe system for the Association for Computational Mechanics (USACM), measurement of tissue refractive index. Advanced 2007 Biomedical and Clinical Diagnostic Systems V (San Jose, CA, Jan. 2007). Progress in Biomedical Optics and Rashid Bashir Imaging: Proceedings of the SPIE, Vol. 6430, 64300 Bliss Professor, University of Illinois (2007) (http://dx.doi.org/10.1117/12.700955). Purdue University Faculty Scholar, 2005-2010 Visiting Professor of Surgery, Harvard Medical School Visiting Professor of Surgery, Shriner's Hospital for Patents Children Visiting Professor of Surgery, Massachusetts General Hospital Bioacoustics Member, United States delegation to Japan for the Second Japan-U.S. Joint Symposium on Nanotechnology in Jones, D., O'Brien, W. D., Feng, A. S., Wheeler, B. C., Advanced Therapy and Diagnostics, Yokohama, Japan, Lansing, C. R., and Bilger, R. C. Intrabody 2003 Communication for a Hearing Aid [Utility Patent Honorary Member, Golden Key International Honor Grant], # US 7206423, Apr. 2007. Society, 2005

48 Education and Mentorship Award, BioMEMS and Ernest W. Thiele Lectureship, University of Notre Dame, Biomedical Nanotechnology World Congress Meeting, 2001 2003 Beckman Associate, University of Illinois Center for Global Indus Technovator Award, MIT Sloan Business Advanced Study, 2002 School and the Indian Business Club, 2003 University Scholar, University of Illinois, 2003 Small Times Magazine Finalist, Innovator of the Year CAST Director's Award, American Institute of Chemical Award, 2005 Engineers, 2003 Agricultural Team Research Award, Purdue University, Curtis W. McGraw Research Award, American Society for 2006 Engineering Education, 2004 Outstanding Paper Award, IEEE Transactions on Control Rohit Bhargava Systems Technology, 2005 List of Teachers Ranked as Excellent by Their Students, CAST Outstanding Young Researcher Award, American University of Illinois at Urbana-Champaign, 2006, 2007 Institute of Chemical Engineers, 2005 Accenture Outstanding Faculty Award for Undergraduate Antonio Ruberti Young Researcher Prize, Institute of Advising, University of Illinois at Urbana-Champaign, Electrical and Electronics Engineers, 2005 2007 Lindsay Distinguished Lecturer, Texas A & M University, Young Investigator Award, Prostate Cancer Research 2005-2006 Program, Department of Defense, 2007 Millennium Chair of Chemical and Biomolecular Engineering, University of Illinois, 2006 Stephen Boppart Excellence in Process Development Research Award, Everitt Award for Teaching Excellence, University of American Institute of Chemical Engineers, 2006 Illinois College of Engineering, 2003, 2005 Fellow, Institute of Electrical and Electronics Engineers, Faculty Early Career Development Program (CAREER) 2007 Award, National Science Foundation, 2004 Young Alumni Achievement Award, University of Illinois Yoram Bresler Department of Electrical and Computer Engineering, Fellow, Institute of Electrical and Electronics Engineers 2005 (IEEE) Tau Beta Pi Outstanding Alumni Award, University of Technion Fellowship, 1995-1996 Illinois, 2005 University Scholar, University of Illinois, 1999 Early Career Achievement Award, Institute of Electrical Associate, University of Illinois Center for Advanced and Electronics Engineers (IEEE) Engineering in Study, 2001-2002 Medicine and Biology Society, 2005 Elected Senior Member, IEEE, 2005 Bertram C. Bruce Excellence in Advising, University of Illinois Engineering University of Illinois Distinguished Teacher/Scholar Council, 2006, 2007 Award, 2006 Visiting Professorship, Raine Medical Research ALISE Pratt-Severn Faculty Innovation Award, 2006 Foundation, 2007 Fulbright Distinguished Chair, National College of Ireland, 2007-2008 Richard D. Braatz Doctoral Thesis Prize, Hertz Foundation, 1994 Sahraoui Chaieb DuPont Young Faculty Award, 1995 Young Scientist Fellowship, Direction des Recherches et Teaching Excellence Award, University of Illinois School Etudes Techniques of the Delegation Generale a of Chemical Sciences, 1997 l'Armement, Ministry of Defense, 1994 Advisors List for Advising Excellence, University of Collins Scholar Award, University of Illinois College of Illinois College of Engineering, 1999, 2002 Engineering, 2001 Xerox Award for Faculty Research, University of Illinois Image of the Week, Image Technology Group, Beckman College of Engineering, 1999 Institute, University of Illinois, Feb. 2001, Sept. 2001 Donald P. Eckman Award, American Automatic Control Strathmore's Who's Who, 2002 Council, 2000 Faculty Early Career Development Program (CAREER) Council of Outstanding Early Career Engineers, Oregon Award, National Science Foundation, 2003 State University, 2000 Grainger Foundation Gift for Emerging Technologies, University of Illinois College of Engineering, 2003

49 Fellow, Center for Advanced Studies and Beckman Fellow, American Association for the Advancement of Fellow, University of Illinois, 2005-2006 Science Who's Who in Engineering Education, 2005 Richard and Margaret Romano Professorial Scholar, University of Illinois, 2004- John C. Chato, Emeritus Alexander von Humboldt Fellowship, 1983-1984, Fellow, American Society of Mechanical Engineers, 1975 1998-1999 Fellow, American Institute for Medical and Biological Treasurer, International Society for Neuroethology, Engineering, 1993 1992-1995, 1995-1998 Postdoctoral Fellow, National Science Foundation, 1961 President, International Society for Neuroethology, Distinguished Engineering Alumnus Award, University of 2001-2004 Cincinnati, 1972 Associate Editor, Journal of Biomechanical Engineering, Leon A. Frizzell, Emeritus 1976-1982 Fellow, Acoustical Society of America Fogarty Senior International Fellow, National Institutes of Fellow, American Institute for Medical and Biological Health, 1978-1979 Engineering Charles Russ Richards Memorial Award, Pi Tau Sigma and Fellow, American Institute of Ultrasound in Medicine American Society of Mechanical Engineers, 1978 Senior Member, Institute of Electrical and Electronics Russell B. Scott Memorial Award, Cryogenic Engineering Engineers Conference, 1979 Engineering Council Advisors List for Outstanding Honorary Visiting Professor, University of New South Advising, University of Illinois, 1995, 1996, 1997, 1998 Wales, Australia, 1986 Andersen Consulting Award for Excellence in Advising, John G. Georgiadis University of Illinois College of Engineering, 1989 Engineering Research Initiation Award, Engineering H. R. Lissner Award, American Society of Mechanical Foundation and American Society of Mechanical Engineers, 1992 Engineers, 1988 Certificate of Appreciation for Outstanding Paper, 46th Presidential Young Investigator Award, National Science Annual International Appliance Technical Conference, Foundation, 1991 1995 American Men and Women of Science, 1992 Engineering Council Advisors List for Outstanding Guest Associate Editor, Journal of Fluids Engineering, Advising, University of Illinois, 1996 1996 Travel Fellowship, Japan Society for the Promotion of Member, Editorial Advisory Board, Journal of Porous Science, 1997 Media, 1996- Dedicated Service Award, American Society of Certificate of Appreciation, American Society of Mechanical Engineers, 2000 Mechanical Engineers, 1998-1999 Fellow, American Society of Heating, Refrigerating, and Engineering Council Award for Excellence in Advising, Air-Conditioning Engineers, 2003 University of Illinois College of Engineering, 1999 Distinguished Alumnus Award, University of Illinois Centre Nacional de la Recherche Scientifique Researcher, Department of Mechanical and Industrial Engineering, Institute of Fluid Mechanics of Toulouse, Toulouse, 2005 France, 1999 Listed in Daily Illini "Incomplete List of Teachers Ranked Jianjun Cheng as Excellent by their Students,” University of Illinois, Competitive Award, Prostate Cancer Foundation, Spring 2001, Fall 2002, Spring 2003 2007-2008 Associate Technical Editor, Journal of Heat Transfer, Faculty Early Career Development Program (CAREER) 2000-2003 Award, National Science Foundation, 2008-2013 Richard W. Kritzer Distinguished Professor, University of Illinois Department of Mechanical and Industrial Howard S. Ducoff, Emeritus Engineering, University of Illinois, 2004-2009 Visiting Biophysicist, University of Lodz, Poland, 1987 Steve Granick Albert S. Feng Fellow, American Physical Society Fellow, Acoustical Society of America SM Young Faculty Award, 1988

50 Fellow, Center for Advanced Study, University of Illinois, Iwona Jasiuk 1990-1991 Guest Editor, Special Issue of Applied Mechanics Award for Special Creativity, National Science Reviews, 1994 Foundation, 1993 Plenary lecture at the Workshop on Phase Distinguished Polymer Lecturer, Lehigh University, 1993 Transformations, Composite Materials and Xerox Award for Faculty Research, University of Illinois Microstructure on “Micromechanics of Composite College of Engineering, 1993 Materials: Influence of Interface, Shape and Geometric Sabbatical Scholar, Kyoto University, Japan, 1994 Arrangement of Fibers,” Institute for Mathematics and Key Tribology Lecturer, Tsinghua University, China, 1996 Its Applications, University of Minnesota, 1995 University Scholar, University of Illinois, 1997 Listed in Marquis Who’s Who in Science and Founder Professor of Engineering, University of Illinois Engineering (2nd & 3rd Editions), 1996 College of Engineering, 1999 Member, Board of Editors, International Journal of Solids Chaire Paris Sciences, City of Paris, France, 2002 and Structures, 1996-2005 Chair-Elect, Division of Polymer Physics, American Listed in Marquis Who’s Who in American Education, (5th Physical Society, 2005 Edition), 1997 Associate, Center for Advanced Study, University of Guest Editor, Special Issue of International Journal of Illinois, 2005 Solids and Structures, 1998, 2001 Chair, Division of Polymer Physics, American Physical Guest Editor, Applied Mechanics in the Americas Vols. 6, Society, 2006 7, 8, Proceedings of the 6th Pan-American Congress of Vice-Chair, Gordon Research Conference on Liquids, Applied Mechanics and 8th International Conference on 2007 Dynamic Problems in Mechanics, Rio de Janeiro, Brazil, 1999 Elizabeth Hsiao-Wecksler Listed in Polish American Who’s Who (1st Edition), 2000 Biology of Aging Research Scholar, American Federation Member, Board of Directors, Society of Engineering for Aging Research and Glenn Foundation, 1998 Science, 2000-2007 New Investigator Recognition Award, Orthopaedic Keynote Speaker, ME '00, The 2000 International Research Society and American Geriatrics Society, Mechanical Engineering Congress and Exposition, 1999 Orlando, Florida, 2000 Fellow, Center for Advanced Study, University of Illinois, Most Helpful Professor Teaching Award, Georgia 2004-2005 Technical University, 2002 Campus Award for Excellence in Guiding Undergraduate Fellow, American Society of Mechanical Engineers, 2003 Research, Honorable Mention, University of Illinois, Vice-Chair, Applied Mechanics Division Composites 2005 Committee, American Society of Mechanical Listed in Daily Illini "Incomplete List of Teachers Ranked Engineers, 2003 as Excellent by Their Students," University of Illinois at Plenary Lecture, “Modeling of Trabecular Bone as a Urbana-Champaign, Fall 2005, 2006 Hierarchical Material," 2nd International Conference on Science & Technology of Composite Materials Michael Insana (COMAT 2003), Mérida, Mexico, 2003 Senior Member, Institute of Electrical and Electronics Member, Board of Editors International Journal of Engineers (IEEE), 2006 Multiscale Computational Engineering, 2003- Fellow, American Institute for Medical and Biological Guest Editor, Special Issue of Mechanics of Materials, Engineering (AIMBE), 2006 2003 Guest Editor, Special Issue of Mechanics of Materials, Eric G. Jakobsson 2004 Undergraduate Advising Award, University of Illinois Chair, Applied Mechanics Division Composites College of Liberal Arts and Sciences, 1989 Committee, American Society of Mechanical Fellow, American Physical Society, 1994 Engineers, 2004 Bioinformatics and Bioengineering Outstanding Member, Board of Editors, Journal of Mechanics of Achievement Award, IEEE, 2007 Materials and Structures, 2005- Member, Board of Directors, Society of Engineering Science, 2000-2007 Vice-President, Society of Engineering Science, 2005

51 President, Society of Engineering Science, 2006 Empire Who's Who of Women in Education, 2006 Member, Editorial Board, International Journal of Academician, World Academy of Ceramics, 2004 Damage Mechanics, 2006- Keynote Lecture, Fourth International Conference on Invited seminar speaker, IT Distinguished Women Advanced Materials (ICAMP-4), Sydney, Australia, Scientists and Engineers Speakers Program, University 2007 of Minnesota, Minneapolis, 2006 Invited Keynote Lecture, Third International Conference Engineering License: Professional Engineers of Ontario, on Alkali Activated Materials, Research, Production and Canada, 2006- Utilization, Prague, Czech Republic, 2007 Representative, U.S. National Committee on Theoretical and Applied Mechanics, Society of Engineering Deborah E. Leckband Science, 2007-2010 Reid T. Milner Professor of Chemical Sciences Member, Scientific Committee, 4th International Fellow, American Institute of Medical and Biological Conference on Science and Technology of Composite Engineering (AIMBE) Materials (COMAT 2007), Rio de Janeiro, Brazil, 2007 Fellow, American Association for the Advancement of Technical Chair, Society of Engineering Science Annual Science (AAAS) Conference, University of Illinois at Urbana- National Science Foundation Research Initiation Award, Champaign, 2008 1993-1996 Advisor (jointly with J. Dantzig) of Natarajan Kumar, 3rd FIRST Award, National Institutes of Health, 1993-1998 place student paper award recipient, Society of Faculty Early Career Development Program (CAREER) Engineering Science Conference, College Station, Award, National Science Foundation, 1995-1999 Texas, 2007 Amoco Lectureship, Stanford University, 1998 Xerox Faculty Research Award, University of Illinois Amy Wagoner Johnson College of Engineering, 1998 Scholarship, Society of Women Engineers/Central Helen Petit Professorship, University of Illinois College of Intelligence Agency, 1993-1994 Liberal Arts and Sciences, 1999-2000 Fontana Scholarship, The Ohio State University Fellow, University of Illinois Center for Advanced Study, Department of Materials Science and Engineering, 1999-2000 1993-1994 University Scholar, University of Illinois, 2001-2004 Scholar, American Society for Materials (ASM), 1995 Plenary Speaker, American Chemical Society Colloids and GANN Fellowship, U.S. Department of Education, Surface Science Symposium, 2001 1996-1998 Keynote Speaker, University of Virginia Bioengineering Paper listed at the Top 10 most downloaded Biomaterials Symposium on Biomechanics of Adhesion, 2002 (IF 5.196) papers, 2007 Provost's Distinguished Lecture Series, University of Texas, Austin, 2003 Neil L. Kelleher Distinguished Lecturer, Cell and Molecular Biology, Pfizer Award in Enzyme Chemistry, American Chemical Boston University School of Dental Medicine, Boston, Society, Division of Biological Chemistry, 2006 2003 A. F. Findeis Award, American Chemical Society, 2006 Britton Chance Distinguished Lecturer in Engineering and Medicine, University of Pennsylvania, 2004 Kyekyoon (Kevin) Kim Fellow, American Institute of Medical and Biological Overseas Member, National Academy of Engineering, Engineering (AIMBE), 2005- Korea, 2002 Fellow, American Association for the Advancement of Science, 2006- Waltraud M. Kriven Fellow, American Ceramic Society, 1995 Zhi-Pei Liang Lifetime Member, America's Registry of Outstanding University Scholar Award Professionals Beckman Fellow, University of Illinois Center for Lifetime Member, Honored Member, Strathmore's Who's Advanced Study, 1997 Who Henry Magnuski Scholar, University of Illinois College of Brunauer Award, American Ceramic Society, 1988, 1991 Engineering, 1999 America's Registry of Outstanding Achievers, 2003-2004 Member, World Academy of Ceramics, 2004

52 Manssour H. Moeinzadeh AIUM William J. Fry Memorial Lecture Award, 2007 Ralph R. Teetor National Educational Award for Teaching 2006 Outstanding Paper Award, IEEE Ultrasonics, Excellence, Society of Automotive Engineers, 1984 Ferroelectronics, and Frequency Control Society, 2007 Campus Award for Excellence in Undergraduate Teaching, Finalist, University of Illinois, 1988, 1989 Michael L. Oelze United States National Committee on Biomechanics, Fellow, National Institute of Health Post-Doctoral Executive Member, 1992- Research, 2002-2004 Centennial Recognition for Exceptional Contribution to American Society for Engineering Education and the Daniel W. Pack Profession of Engineering, 1993 Excellence in Teaching Award, School of Chemical Biomedical Engineering Division Chair Award, American Sciences, University of Illinois, 2000 Society of Engineering Education, 1993 Selection to Frontiers of Engineering Symposium, Development Program Award for Collaborative Research National Academy of Engineering, 2002 and Educational Projects with Overseas Institutions, Faculty Early Career Development Program (CAREER) United Nations, 1994-1995, 1995-1996 Award, National Science Foundation, 2002 List of Teachers Rated Excellent by Their Students, Excellence in Teaching Award, School of Chemical University of Illinois, 2000, 2001, 2002 Sciences, University of Illinois, 2003 Outstanding Advisor Award, University of Illinois, 2003 3M Young Faculty Award, 2003-2006 Beckman Fellow, Center for Advanced Study, University Mark E. Nelson of Illinois, Urbana-Champaign, 2004-2005 Beckman Fellow, University of Illinois Center for Multi-Year Faculty Achievement Award, College of Advanced Study, 1993 Engineering, University of Illinois, Urbana-Champaign, Fellow, American Association for the Advancement of 2007 Science (AAAS), 2006 Nathan D. Price William D. O'Brien, Jr. Bioengineering Department's Nominee for Campus Founding Fellow, American Institute of Medical and Dissertation Prize, University of California, San Diego Biological Engineering (UCSD), 2005-2006 Fellow, Acoustical Society of America Sam E. and Kathleen Henry Postdoctoral Fellowship, Fellow, American Institute of Ultrasound in Medicine American Cancer Society, 2005-2007 (Alum) Tomorrow's Principle Investigator Award, Genome Fellow, Institute of Electrical and Electronics Engineers Technology, 2007 (IEEE) President, American Institute of Ultrasound in Medicine, Klaus Schulten 1988-1991 Parker Fellow, 1970-1972 President, IEEE Sonics and Ultrasonics Group, 1982-1983 Nernst Prize, Deutsche Bunsengesellschaft fur Treasurer, World Federation of Ultrasound in Medicine Physikalische Chemie, 1981 and Biology, 1991-1994 Ludwig-Schaefer Award, Columbia University, 1985 Honorary Member, Society of Vascular Technology DuPont Young Faculty Award, 1989 Centennial Medal, IEEE, 1984 Arnold O. Beckman Award, University of Illinois Center Editor-in-Chief, IEEE Transactions on Ultrasonics, for Advanced Study, 1989 Ferroelectrics, and Frequency Control, 1985-2001 Fellow, American Physical Society, 1993 Distinguished Lecturer, IEEE Ultrasonics, Ferroelectrics Mr. & Mrs. James R. Martin University Scholar, and Frequency Control Society, 1997-1998 University of Illinois, 1996 IEEE Third Millennium Medal, 2000 Swanlund Endowed Chair, University of Illinois, 1996 Donald Biggar Willet Professor of Engineering, College of Humboldt Award, Alexander von Humbolt Foundation, Engineering, University of Illinois, 2003- 2004 Distinguished Service Award, IEEE Ultrasonics, Scientific Advisory Board of the Max-Planck-Institute Ferroelectrics, and Frequency Control Society, 2003 Dortmund (Germany) Engineering Council Award for Excellence in Advising, University of Illinois College of Engineering, 2004 MERIT Award, National Institutes of Health, 2006

53 Mark A. Shannon Special Creativity Extension, National Science Listed in Daily Illini "Incomplete List of Teachers Ranked Foundation, 2002-2004 as Excellent by Their Students," University of Illinois, Theophilus Redwood Lecturer, Analytical Division, Royal Fall 1998; Spring 2002, 2004 Science of Chemistry, 2007 Engineering Council Award for Excellence in Advising, Pittsburgh Analytical Chemistry Award, Society of University of Illinois College of Engineering, 1995, Analytical Chemists of Pittsburgh, 2007 1998, 2002, 2008 Associate Editor, Analytical Chemistry, 2007 Faculty Early Career Development Program (CAREER) Engineering Research and Development Corp's Award for Award, National Science Foundation, 1997 Outstanding Team Effort, Army Corp of Engineers, Accenture Award for Excellence in Advising, University 2007 of Illinois College of Engineering, 2002, 2003 Multi-Year Faculty Achievement Award, University of Kimani C. Toussaint Illinois College of Engineering, 2003 Ruth Hayre Scholarship, 1991 Kritzer Faculty Scholar, University of Illinois Department Philadelphia Mayor's Scholarship, 1991-1996 of Mechanical and Industrial Engineering, 2003-2006 William Penn Fellowship, 1994-1995 Xerox Award for Faculty Research, University of Illinois House Community Service Award, DuBois College, 1996 College of Engineering, 2004 Stone and Webster Scholarship, 1997 Willett Faculty Scholar Award, University of Illinois Gates Millennium Scholarship, 2000-2004 College of Engineering, 2004-2007 FOCUS Fellow, Georgia Institute of Technology, 2003 James W. Bayne Professor in Mechanical and Industrial Minority Postdoctoral Fellowship in Biology, National Engineering, University of Illinois, 2006 Science Foundation, 2005-2007 BP Award for Innovation in Undergraduate Instruction, 18th Annual Kavli Frontiers of Science Symposium, University of Illinois College of Engineering, 2006 National Academy of Science, 2006

Jonathan V. Sweedler Ning Wang New Faculty Award, Henry and Camille Dreyfus Alumni Scholarship, Harvard School of Public Health, Foundation, 1991 1988-1989 David and Lucile Packard Foundation Fellowship in Scholander Award, American Physiological Society, 1991 Science and Engineering, 1992 Caroline tum Suden Professional Opportunity Award, Young Investigator Award, National Science Foundation, American Physiological Society, 1991 1992 Beckman Fellow, University of Illinois Center for Bruce C. Wheeler Advanced Study, 1993 Fellow, American Institute for Medical and Biological Searle Scholars Awards, 1993 Engineering Fellow, A. P. Sloan Foundation, 1995 Fellow, IEEE Camille Dreyfus Teacher Scholar Award, Henry and Editor in Chief, IEEE Transactions on Biomedical Camille Dreyfus Foundation, 1996 Engineering University Scholar, University of Illinois, 1997 Honorary Knight of St. Pat, University of Illinois College Young Analytical Chemist, Analytical Division of the of Engineering, 1999 American Chemical Society, 1997 Outstanding Medical Scholar Advisor, 2004 Benidetti-Pichler Award in Microanalysis, American Microchemical Society, 1999 Gerard C. L. Wong Gill Prize, 2000 Beckman Young Investigator Award, University of Fellow, American Association for the Advancement of Illinois, 2001 Science, 2001 Donald Burnett Teacher of the Year Award, University of Lycan Professorship in Chemistry, University of Illinois, Illinois Materials Science and Engineering Department, 2001 2003 The Heinrich-Emanuel Merck Prize, Merck Company, Alfred P. Sloan Fellowship, University of Illinois, 2004 2002 Top Physics News Stories, American Physical Society Instrumentation Award, American Chemical Society News, 2003, 2004 Analytical Division, 2002 Xerox Award for Faculty Research, University of Illinois College of Engineering, 2005

54 Invited Participant, 2006 National Academy of Xerox Award for Faculty Research, University of Illinois Engineering Frontiers Symposium, 2006 College of Engineering, 2005 Prostate Cancer Foundation Competitive Award, 2007 Dupont Young Professor Award, 2005 Taipei Academica Sinica International Workshop on Soft Helen Corley Petit Scholar, University of Illinois College Matter and Biophysics, 2007 of Liberal Arts and Sciences, 2006 National Science Foundation–Department of Science and University Scholar, University of Illinois, 2007 Technology U.S.-India Nanoscience & Engineering Investigator Award, Division of Biochemical Technology, Workshop, 2008 American Chemical Society (ACS), 2008 Xerox Award for Faculty Research, University of Illinois College of Engineering, 2008

James F. Zachary Diplomate, American College of Veterinary Pathologists Editor-in-Chief, Veterinary Pathology, 1994-1999

Yuanhui Zhang Outstanding Paper Award, American Society of Agricultural Engineers, 1989, 2001 Honorarium Professorship, Beijing University of Agricultural Engineering, China, 1994 Honorarium Professorship, Shadong Institute of Technology, China, 1994 Everitt Award for Teaching Excellence, University of Illinois College of Engineering, 1997 General Electric Scholar, University of Illinois College of Engineering, 1997 Blue Ribbon Award, American Society of Agricultural Engineers, 1998 Teaching Excellence Award, University of Illinois Department of Agricultural Engineering, 1999 Superior Paper Award, American Society of Agricultural Engineers, 2001 Annual Paper Award, American Society of Heating, Refrigeration and Air-Conditioning Engineers, 2002 Fellow, National Center for Supercomputing Applications, 2004 Bliss Faculty Scholar Award, University of Illinois College of Engineering, 2005 Distinguished Service Award, American Society of Heating, Refrigeration and Air Conditioning Engineers, 2007

Huimin Zhao Dow Special Recognition Award, 1999-2000 Collins Scholar, University of Illinois College of Engineering, 2001 Faculty Early Development (CAREER) Program Award, National Science Foundation, 2004-2009 Excellence in Teaching Award, University of Illinois School of Chemical Sciences, 2004 Beckman Fellow, University of Illinois Center for Advanced Study, 2005-2006

55