Activity

American Recovery and Reinvestment Act 2009

Preliminary Notice, Proposals and Awards





Stimulus Award Tracking

UNC Tomorrow legend: GR = Global Readiness, AC = Access to HE, K12 = Public Education, ET = Economic Transformation, HE = Health, EV = Environment, OE = Outreach and Engagement



Status

Date

Amount Amount Prelim. UNCT Submitted/A

Campus PI Requested Awarded Notice Prop. Award Code Sponsor Title Summary Begin Date End Date CFDA# SPS # warded

The College of Agriculture and Life Sciences at North Caorlina State University seeks to obtain

a Leica LMD7000 fluorescent microscope equipped for laser microdisection (LMD) and image

quantification to support molecular analyses of biological specimens from whole organisms at

the cellular level. The LMD7000 provides the highest cutting precision of any LMD and allows

realtime cutting the a ?move and cut? setting. When a high-energy laser pulse hits the tissue,

a fast reaction limited to the focus of the laser light called ?cold ablation? takes place. This

process is very fast, and surrounding tissue is not impaired or heated. Single laser pulses,

strung together, form the cutting line of the system. Only Leica uses high-precision optics to

steer the laser beam along the desired cut line on the tissue, greatly improving cutting

precision. Importantly, the Leica LMD7000 is the first LMD system that integrates these

Acquisition of a Fluorescent contradicting approaches within one system. By controlling the repetition rate, the user can

Microscope Equipped For Laser adjust the laser according to the specimen and make narrow, powerful, and fast cuts with a

Threadgill, GR, AC, National Institutes Capture Microdissection and single system. This overcomes many limitations of previous systems that use fixed laser

NCSU David $293,630 $0 X HE, OE of Health Quantitative Morphology Analysis strengths. The UV offset corrects the focus of the UV laser with respect to the focus of the 4/1/2010 3/31/2011 93.389 2009-1874 3/30/2009

Summary/Abstract: We propose to purchase an Illumina Genomic Analyzer IIX sequencing

platform. The equipment brings deep-read sequencing technology to North Carolina State

GR, AC, National Institutes Acquisition of Next-Gen sequencing University (NCSU), which is needed for continued research competitiveness and to train the

NCSU Schaff, Jennifer $499,800 $0 X ET, HE, OE of Health at NCSU next generation of students in modern biomedical genomic research. The equipment will be 4/1/2010 3/31/2011 93.389 2009-1909 4/2/2009







Northeast

Workforce

Development Board

Sykes, Wanda GR, AC, (NC) (US Dept. of

NCSU D. $300,000 $0 X ET, HE, OE Commerce) WIA Workforce Readiness Summer workforce development program for youth ages 16-24 in a 10 county region 4/1/2009 8/31/2009 17.259 2009-1911 4/2/2009

This application addresses broad Challenge Area (11) Stem Cells and the specific challenge

topic of ?11-EB-106 Technologies for Expanding Stem Cells and Producing Engineered Tissue?.

The long-term goal of this project is the development of propagation systems and controlled

microenvironments for generation of stable populations of human pluripotent stem cells

(hPSCs) that not only maintain their undifferentiated state but also their genomic integrity.

The consequences of a propagation system that generates a genomically unstable hPSC can be

devastating. When hPSC lines are either intentionally selected for specific phenotypes or

genotypes, these cells could also be undergoing unintended selection for altered karyotype.

Engineering cell phenotypes and function based on dynamic cell-cell, cell-surface and adjacent

microenvironment interactions will be critical to generation of stable hPSCs. The specific

hypothesis is that human fibroblast-derived extracellular matrix (hECM) in hyaluronic acid (HA)-

Virginia based ?fall-apart? hydrogels promote stable expansion of hPSCs in suspension culture. We

Commonwealth Naturally Derived Biomaterials for base that hypothesis on the observations that (a) enzymatic passaging of cells using trypsin or

Loboa, University (National Stable Propagation of Human collagenase leads to hPSCs exhibiting abnormal karyotype (b) hECM promotes stable

NCSU Elizabeth G. $200,000 $0 X HE, OE Institutes of Health) Pluripotent Cells expansion of hPSCs in feeder-free settings and (c) ?fall-apart? hydrogels utilize a convenient 9/30/2009 9/29/2011 93.701 2009-1930 4/6/2009









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American Recovery and Reinvestment Act 2009

Preliminary Notice, Proposals and Awards







Diabetes, a leading cause of morbidity and mortality, is projected to increase dramatically

over the coming decades. Medication treatment guidelines must be designed to

simultaneously control multiple risk factors such as cholesterol, blood pressure, and glucose

levels. Imperfect adherence to medication presents a serious barrier to successful

implementation of theoretically optimal treatment guidelines. This grant will study optimal

medication initiation for Type 2 diabetes in older patients with a focus on how uncertainty in

the degree of adherence and the resulting medication effects influence optimal treatment

guidelines. We will also investigate how competing risks from other comorbidities influence

Mayo Foundation Development of Medication the optimal treatment guideline. We will evaluate whether medication prioritization changes

GR, AC, (National Institutes Algorithms for Complex Elderly for older patients and how such changes depend on the degree of adherence and presence of

NCSU Denton, Brian $233,892 $0 X HE, OE of Health) Patients comorbidities. 10/1/2009 9/30/2011 93.701 2009-1988 4/13/2009

Combination chemotherapy is a mainstay of treatment for blood cancers, but often has

significant side effects and is not curative, likely because treatment fails to eradicate the root

cause of disease, the leukemic stem cell. In traditional combination chemotherapy regimens,

patients are exposed to maximum tolerated doses of each drug. Laboratory data, however,

indicate that effectiveness could be maintained with less toxicity if drugs could be

administered in amounts found to optimally inhibit growth of leukemic cells in culture (drug

synergy). However, it is currently not feasible clinically to deliver drug combinations in precise

concentrations and ratios. Furthermore, cancer drugs typically attack both tumor and normal

dividing cells, and tumor cells can survive by actively pumping out the drug. To address these

issues, a novel drug delivery technology has been devised based on a common plant virus

found in the soil. This virus has several unique drug-delivery properties: a) it occurs naturally,

is non-toxic, does not infect human cells and can be modified in many ways to enhance

Duke University Nanoparticle-Targeted specificity for tumor cells, b) drugs are easily loaded and don?t leak out; c) there is a

(National Institutes Combination Chemotherapy For mechanism for release of drug cargo once inside the tumor cell; d) encapsulated drugs cannot

NCSU Franzen, Stefan $290,300 $0 X ET, HE, OE of Health) AML Stem Cells be easily pumped out, and e) the virus can deliver drugs directly to the cell nucleus, where 9/30/2009 9/29/2011 93.701 2009-1998 4/14/2009

In this RC1 application we are proposing to carry out metabolomic profiling of unique plasma

samples to be obtained from participants in the LiTMUS study to address the following specific

aims are: A.1.Primary Aim: To identify metabolomic signatures predictive of Li+OPT

effectiveness and specific side effects. A.1.1.Hypothesis 1: Plasma levels of candidate

metabolites capturing the overall state of intermediary, anabolic and other biosynthetic

metabolic pathways differ significantly between patients classified as remitted and tolerating

lithium well based on improvement on Clinical Global Impression-BP severity scale (CGI-BP-S)

and fewer Necessary Clinical Adjustments (NCAs) over the course of 6 months.

A.1.2.Hypothesis 2: Development of side effects such as anti-thyroid antibodies and

perturbations in kidney function are linked to specific Metabolomic signatures emerging from

Duke University different levels of metabolites in patients having or not these side effects. A.1.2.Hypothesis 3:

Medical Center To identify biomarkers predictive of Lithium response by comparing the baseline and two

Zeng, Zhao- GR, AC, (National Institutes Pharmacometabolomics of Lithium weeks plasma metabolomic profile of in a subset of patients available from the Li+OPT and

NCSU Bang $32,990 $0 X ET, HE, OE of Health) Response in Bipolar Disorder OPT groups. A.2. Secondary Aim: To identify potential metabolomic signatures of depression, 9/30/2009 9/29/2011 93.701 2009-2004 4/14/2009

Alzheimer?s disease (AD) is a major public health and there is an urgent need to validate

biomarkers relevant to early detection and disease progression. AD is accompanied by

neurochemical alterations in multiple systems such as beta-amyloid, tau, inflammation,

oxidative stress, neurotransmitters, energetics, and cellular lipds. Metabolomics, the study of

metabolism at the global or ?-omics? level, is a new but rapidly growing field that has been

earmarked as an important area to develop under the NIH roadmap initiative. In this

collaboration between Duke and the University of Pennsylvania ADRC, we plan to use

complementary and targeted metabolomics technologies to capture biochemical changes in

CSF of a well characterized cohort of 160 subjects (40 AD patients, 40 MCI, 40 controls, 40

neurologic controls). This cohort is unique since it has already been recruited and studied at

Duke University the UPenn using other biomarkers such as CSF amyloid-beta and tau, MRI volumetrics, FDG

Medical Center PET scans, and neurocognitive testing. Hence, there is high confidence that the study will be

Zeng, Zhao- GR, AC, (National Institutes Metabolomic Markers of Preclinical completed in 2 years. Specifically we will test hypotheses that CSF metabolomic signatures can

NCSU Bang $68,920 $0 X ET, HE, OE of Health) and Early Alzheimer's Disease separate AD and MCI subjects from controls, and can predict cognitive decline over a 2 year 9/30/2009 9/29/2011 93.701 2009-2009 4/15/2009









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American Recovery and Reinvestment Act 2009

Preliminary Notice, Proposals and Awards





Statins are the largest single class of drugs prescribed for CVD prevention, with over 120

million prescriptions and over $13 billion in sales in 2003. Statins are HMG CoA reductase

inhibitors, and the primary clinical rationale for the use of statins is to reduce the level of LDL-

cholesterol and, thereby, to reduce CVD risk. This effect is due in large part to increased LDL

and IDL clearance as a result of the upregulation of LDL receptors. Multiple intervention trials

with statin drugs have demonstrated a remarkable degree of consistency in their ability to

reduce risk for both CVD and stroke by an average of approximately 1/4 to 1/3. Nevertheless,

in all of these trials, residual CVD risk remains high (60-75%), and potential drug-related

toxicity, while infrequent, is a significant concern ? i.e., there is large individual variation in the

drug response phenotype after statin therapy. Complicating our understanding of past trials

Duke University and future clinical trials, the most widely accepted immediate surrogate endpoints for

Medical Center cardiovascular disease trials, LDL cholesterol and HDL cholesterol, have recently failed to

Zeng, Zhao- GR, AC, (National Institutes Metabolomic Signatures as predict clinical benefit following drug intervention. The application of a biomarker to predict

NCSU Bang $76,434 $0 X ET, HE, OE of Health) Predictors of Statin Response treatment response to statins therefore represents a major opportunity for translational 9/30/2009 9/29/2011 93.701 2009-2020 4/15/2009

The Lila Lab team will take primary responsibility for the activity-guided fractionation,

dereplication, and structural characterization of bioactive compound leads with activity

against malaria and other infective disease targets. As such, the Lila Lab team will work in

close coordination with partnering laboratories responsible for in vitro screening of

phytochemical mixtures and isolated compounds (U South Florida for antimalarial screening,

USFQ for antileishmanial screening, and Rutgers University for other lead compounds

screening), The Lab will accomplish activity-guided fractionation of prioritized extracts from

Central Asia, using a customized preparatory HPLC protocol established in our laboratory. The

HPLC effluent will be analyzed using LC MS, and mass analysis will be performed using

quadrupole ion trap and time-of-flight (TOF) analyzer. Libraries of plant natural product

chemistry obtained both commercially and in our databases will be used to dereplicate the

phytochemical leads. For complete structural characterization of high priority leads, once

Rutgers University Novel Antimalarial and dereplication process has been completed and the novelty of the structure is determined, we

GR, AC, (National Institutes Antiinfective Pharmacological will utilize a comprehensive, state of the art NMR suite (400-950 MHz) available in the Core

NCSU Lila, Mary Ann $196,001 $0 X ET, HE, OE of Health) Leads from Plants Laboratory of the NCRC. As resident faculty on the campus, our laboratory team has 10/1/2009 9/30/2011 93.701 2009-2029 4/16/2009

The pathogenesis of fibrotic lung disease involves the inability of proliferating alveolar type II

cells (AT2) to differentiate effectively into type I (AT1) cells, leading to faulty epithelial repair,

irreversible damage, loss of function, and fibrosis. The mechanisms that normally control this

process are not fully understood, so potential regulatory molecules or pathways that may be

altered in fibrotic pulmonary diseases have not been elucidated. We propose that the key to

normal alveolar cell differentiation is the relative sulfation of the extracellular matrix (ECM)

microenvironment underlying alveolar cell types. This in turn controls expression of two

important differentiation factors: a member of the forkhead (Fox) family of transcription

factors and specific wingless (Wnt) signaling pathways. These factors act in conjunction with

expression and signaling of transforming growth factor � (TGF�), which enhances Wnt

signaling targets, to collectively drive the cell differentiation process and establish stable

alveolar phenotypes. In this proposal, we will show that following proliferative events

National Institutes Alveolar Basement Membrane/Cell associated with re-epithelialization in the alveolus, there is a critical, dynamic balance

NCSU Sannes, Philip L. $225,720 $0 X HE, OE of Health Interactions in the Lung between alveolar epithelial cells and their ECM microenvironment. This is significantly 4/1/1992 3/31/2014 93.838 1991-1541 4/16/2009









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American Recovery and Reinvestment Act 2009

Preliminary Notice, Proposals and Awards





The current application is specifically designed to build additional capabilities within the

"Metabolomics Network for Drug Response Phenotype" to enable integration of

metabolomics and pharmacogenomics data to achieve a deeper understanding of mechanisms

implicated in drug-response variation towards a more personalized approach to therapy.

Metabolomics is the study of metabolism at the "global" level and involves studies of the

"metabolome", the entire repertoire of small molecules present in cells and/or tissues. The

identities, concentrations and fluxes of these compounds represent the final product of

interactions among gene sequence, gene expression, protein expression and the cellular

environment, an "environment" that in the clinical setting includes drug exposure. We believe

that the inclusion of Metabolomic data as an additional, and highly informative "intermediate

phenotype" might significantly enhance our ability to understand and predict individual

Duke University variation in response to therapeutic agents. In this supplemental application we propose to

Medical Center add informatics and pathway analysis capabilities that can accelerate significantly the effort of

Zeng, Zhao- GR, AC, (National Institutes Metabolomics Network For Drug the network creating and retaining jobs in-line with the Recovery Act Funds for Administrative

NCSU Bang $27,492 $0 X ET, HE, OE of Health) Response Phenotype Supplements (NOT-OD-09-056). Additionally we propose to develop standards that can 12/14/2008 6/30/2011 93.701 2009-1978 4/16/2009

Viral myocarditis affects >5% of the human population, usually with no clinical signs. However

in infants it is often fatal, and in young adults it can progress to a chronic disease requiring

heart transplantation. Investigations proposed here may provide new avenues for therapeutic

National Institutes The Cardiac Interferon Response to intervention. Funds will be used to employ one technician and purchase supplies, consistent

NCSU Sherry, Barbara $101,072 $0 X ET, HE, OE of Health Reovirus Infection with the goals of the ARRA. 7/1/2004 4/30/2010 93.701 2004-0472 4/17/2009





Electrochemical double layer capacitors (EDLCs), or supercapacitors, store energy through

ionic interactions with charged, high specific surface area (SSA) electrodes. They can

complement or replace batteries when high power delivery or uptake is needed. The primary

limitation of EDLCs is their relatively low energy density. The goal is to optimize EDLC energy

density without comprising power delivery, device lifetime, etc. Energy density can be

improved through optimization of the properties of the electrode-electrolyte double layer

SISGR: The Influence of Electrolyte and/or increasing operating voltage. For high SSA carbon electrode EDLCs, the double layer

Structure and Electrode properties are determined by the morphology of the electrode (e.g., surface area and pore

Morphology on the Performance of size) and the physical interactions between the electrode and electrolyte. The operating

Ionic-Liquid Based Supercapacitors: voltage is largely determined by the electrochemical stability of the electrolyte. A molecular-

Henderson, University of Utah A Combined Experimental and level understanding of bulk electrolyte and electrode-electrolyte interactions is therefore

NCSU Wesley $575,804 $0 X GR, EV (US Dept. of Energy) Simulation Study necessary and will be undertaken for further improvements in properties and performance. 11/1/2009 10/31/2012 81.049 2009-2062 4/20/2009

Populations of eastern oysters in North Carolina have reached historic lows, and the NC DMF

is building new oyster reefs in Pamlico Sound to be used as unfished, broodstock reserves for

oyster restoration (Street et al. 2005). Little is known about oyster population dynamics within

each reserve, the potential for reserves to persist as a network of distinct subpopulations

connected by larval dispersal (i.e., a metapopulation), or the ability of reserves to seed other

areas in Pamlico Sound with oyster larvae. North Carolina State University will team with the

North Carolina Coastal Federation and North Carolina Division of Marine Fisheries to (1) assess

North Carolina the ecological performance of this restoration effort, and (2) quantify the impact of this

Coastal Federation restoration effort on species of concern that use oyster reefs as essential fish habitat. The NC

(National Oceanic & Division of Marine Fisheries will (3) quantify the amount of oyster acres restored. A related

Atmospheric study led by Brian Efland and Jack Thigpen, both recreational fishing specialists with NC Sea

Administration Ecological Performance Measures Grant, will (4) quantify changes in recreational angling use in Pamlico Sound as a function of

Eggleston, (NOAA) - National of Large-Scale, Sub-Tidal Oyster this oyster restoration effort. The proposed oyster restoration effort will help to stabilize the

NCSU David B. $285,382 $0 X ET, HE, OE Ocean Service) Restoration oyster metapopulation in Pamlico Sound by presumably increasing overall larval output and 5/1/2009 12/31/2010 11.463 2009-2077 4/22/2009









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American Recovery and Reinvestment Act 2009

Preliminary Notice, Proposals and Awards





This proposed research will address the Challenge Area (02) Bioethic and the Challenge Topic:

02-OD(OSP)-101* Unique Ethical Issues Posed by Emerging Technologies. This study will

document the ethical perceptions of freshmen, seniors, graduate students, and researchers in

Biomedical Engineering, Pharmacology, Materials Science, and Chemistry. Measurements will

be made of perceptions of risks, benefits, regulations, and critical reasoning (reflective

judgment). The field of nanomedical technology has emerged from interdisciplinary research

teams with a speed that has never been experienced before in modern science.

Advancements in nanoscale science and medicine have resulted in part because of new tools

and techniques that allow for specific and targeted manipulation of materials at the molecular

and atomic levels. Nanotechnology?s use in health care may present unique social and ethical

issues that have never been considered before. Furthermore, the ability to directly intervene

Ethics of Nanomedical in human health with constructed nanoscale materials raises new questions about risks,

Technologies: Perceptual benefits, and safety regulations. Most new nanotechnology advancements have resulted from

Jones, Melissa National Institutes Differences Across Domains and teams of researchers from distinct fields of study who have traditionally worked within

NCSU G. $655,281 $0 X HE, OE of Health Degrees of Expertise separate communities of practice. We know little about how researchers within these 10/1/2009 9/30/2011 93.701 2009-2087 4/22/2009

Our proposal titled "Population genetics of transgenes in insect vectors" enabled us to move

ahead with developing a comprehensive modeling framework that can be used by both

theoretical and empirical researchers in determining autocidal and strain replacement

approaches that are most likely to successfully suppress specific insect-borne diseases in

specific regions. We designed our models to encompass a range of detail and goals. The initial

models that we developed were very general and examined basic genetic strategies. We used

results of these initial models to further examine the concepts of genetic pest management

and to make these concepts accessible to a broad scientific audience. A set of intermediate

complexity models that include age and spatial structure of the insect vector species have

recently been completed. The most biologically rich model was developed to fit the biology of

Aedes aegypti, the principal vector of dengue virus (DV). Our proposal specifically stated that

we would 1) develop computer simulation models that were accessible to empirical

researchers in vector biology and others interested in this area of work. 2) use outputs of our

GR, AC, National Institutes Population Genetics of Transgenes models to determine which biological parameters had strong effects on model outputs and

NCSU Gould, Fred L. $99,965 $0 X ET, HE, OE of Health in Insect Vectors required more accurate parameter estimation. 3) develop novel gene drive strategies. We 12/1/2003 5/31/2010 93.701 2003-1335 4/23/2009

Aberrant DNA promoter methylation, an emerging hallmark of cancer, is affected by

environmental exposure and alters gene expression without changing DNA sequence. Changes

in DNA methylation, therefore, appear to constitute an important link between environmental

exposure and disease risk. For the particular case of pesticides, we have previously shown in

an Inuit population, a highly pesticides-exposed population, that higher plasma levels of

pesticide were associated with DNA methylation aberrations. We also demonstrated that

treatment of human blood cells in vitro with pesticides increased methylation of the RASSF1A

promoter. RASSF1A is a tumor suppressor gene. The ultimate goal of my research is to

increase our understanding between pesticide exposure and cancer risk. Based upon the

hypothesis that pesticides increase cancer risk in man by altering DNA methylation, the

specific aims of this research are to: 1) Determine whether pesticide exposure alters DNA

methylation in blood cell DNA, 2) Examine whether pesticide exposed cancer cases have DNA

Northwestern methylation patterns similar to those seen in high pesticide exposed individuals, 3) Investigate

Wallace, University (National DNA Methylation Alterations in whether pesticides can directly affect the methylation of specific genes. This research is

NCSU Andrew Daniel $90,802 $0 X HE, OE Institutes of Health) Response to Pesticide Exposures important and timely. With our increasing reliance upon pesticides, their untoward effects will 10/1/2009 9/30/2010 93.701 2009-2092 4/23/2009



The goal of this project is to measure the impact of an established, research-based, reform

Georgia Institute of introductory electromagnetism curriculum on student problem solving. We will measure

Technology Measuring the Impact on Problem quantitative problem solving ability both on exam problems given in the classroom, and

Kohlmyer, (National Institutes Solving of a Cognitive Science- problems given in a more formal experimental setting. Data will be analyzed based on coding

NCSU Matthew A $34,364 $0 X ET of Health) Based Physics Curriculum student work, for correctness, use of physics principles, and appearance of common errors. 9/30/2009 9/29/2011 93.701 2009-2095 4/23/2009



University of

California - San New therapies will be tested on rhodopsin transgenic pigs. These pigs are a model of retinitis

Petters, Robert Diego (National Drug Therapy in Rhodopsin pigmentosa. Delay of symptoms may indicate a potential treatment that could be applied to

NCSU M. $73,010 $0 X HE, OE Institutes of Health) Transgenic Pigs humans. 9/30/2009 9/29/2010 93.701 2009-2096 4/23/2009









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American Recovery and Reinvestment Act 2009

Preliminary Notice, Proposals and Awards





One of the crucial issues in designing randomized controlled clinical trials is to calculate

sample size needed in the study. Survival models, such as the proportional hazards (PH) model

and competing risk model, are used widely in disease studies. However, the existing method

and software for the sample size calculation in survival analysis only considering the treatment

efficacy. To our knowledge, there is no existing method and software can provide the power

and sample size calculation of the PH model with time varying predictor with or without

competing risk. In order to fill in this gap, we are going to develop a method for the power and

sample size calculation in the PH model with time varying predictor. The method will be

extended to the competing risk model. Furthermore, the user friendly software will be

developed during this grant period with complete user manual. Therefore, the proposed

method provide a useful tool for investigators to explore the optimal sample size accounting

for various dynamic association between the time varying predictor and the user friendly

University of South Sample Size Methods and Software software solves the computational issue in the power and sample size calculation in the

Carolina (National in Survival Trials For Obesity proposed methods. Thus the researchers and practitioners can apply the proposed method in

NCSU Lu, Wenbin $244,933 $0 X HE, OE Institutes of Health) Diseases their study very easily. 9/30/2009 9/29/2011 93.701 2009-2097 4/23/2009



This project will use Pro-Bubbles to enhance the use of ultrasonic imaging for the treatment of

prostate cancer. To accomplish these aims we will: 1) Conduct ultrasound studies to

determine power output requirements for activating ?pro-bubbles into bubbles; 2) Optimize

University of Pro-Bubbles For Ultrasound acoustic parameters required for radiation force assisted localization and marginalization of

Arizona (National Imaging and Treatment of Prostate pro-bubbles; and 3) image activated pro-bubbles in vivo to determine scattering capabilities

NCSU Dayton, Paul A. $399,026 $0 X HE, OE Institutes of Health) Cancer and sensitivity to imaging utilizing optimized ligands, pro-bubbles, and ultrasound. 9/30/2009 9/29/2011 93.701 2009-2101 4/23/2009





Electrochemical double layer capacitors (EDLCs), or supercapacitors, store energy through

ionic interactions with charged, high specific surface area (SSA) electrodes. They can

complement or replace batteries when high power delivery or uptake is needed. The primary

limitation of EDLCs is their relatively low energy density. The goal is to optimize EDLC energy

density without comprising power delivery, device lifetime, etc. Energy density can be

improved through optimization of the properties of the electrode-electrolyte double layer

SISGR: The Influence of Electrolyte and/or increasing operating voltage. For high SSA carbon electrode EDLCs, the double layer

Structure and Electrode properties are determined by the morphology of the electrode (e.g., surface area and pore

Morphology on the Performance of size) and the physical interactions between the electrode and electrolyte. The operating

Ionic-Liquid Based Supercapacitors: voltage is largely determined by the electrochemical stability of the electrolyte. A molecular-

Henderson, University of Utah A Combined Experimental and level understanding of bulk electrolyte and electrode-electrolyte interactions is therefore

NCSU Wesley $636,179 $0 X GR, EV (US Dept. of Energy) Simulation Study necessary and will be undertaken for further improvements in properties and performance. 11/1/2009 10/31/2012 81.049 2009-2062 4/27/2009



The goal of this project is to measure the impact of introducing computational modeling in an

introductory science. We will make comparative quantitative measurements on large numbers

of students in introductory physics courses with and without computation to address whether

Georgia Institute of Measuring the Impact of the use of computational modeling changes the way students think about complex problems,

Technology Computational Modeling on and how student proficiency with computation impacts problem solving. Data from student in-

Kohlmyer, (National Institutes Scientific Thinking in an class work and from student work in more formal experimental setting will be analyzed to

NCSU Matthew A $34,364 $0 X ET of Health) Introductory STEM Course determine the frequency of application of computational methods. 9/30/2009 9/29/2011 93.701 2009-2132 4/28/2009









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American Recovery and Reinvestment Act 2009

Preliminary Notice, Proposals and Awards





The incidence of asthma, especially among children, has dramatically increased in the United

States over the past 30 years, with annual health care cost exceeding $16 billion. Relying on a

new targeting methodology for inhaled drug-aerosols (Kleinstreuer-Seelecke, US patent

pending), optimal asthma-drug delivery to severely inflamed lung sites of children is proposed.

Collaborators on the proposed work include PI Prof. Mark Witten (Pediatrics Laboratory, UA,

Tucson, AZ), Dr. Roni Grad (Pediatric Pulmonary Division, UA), and Prof. S. Hyun (Medical

Image Conversion, Mercer University). The specific aims are as follows: (i) Develop a realistic

and accurate simulation model and validate the computational air-particle dynamic data with

experimental observations using three representative lung casts made from deceased 5-10

year-old children, i.e., the oral-tracheobronchial airways down to Generation 9. A 99mTc-DTPA

Experimental/Computational radioactive tracer will be administered to various particle deposition areas under normal and

Analyses For a Rudimentary Smart pathological inhalation conditions. These studies will provide a predictive computer simulation

University of Inhaler Device For Targeted Drug- model and addresses the problem of subject variability. (ii) For optimally targeted air-particle

Kleinstreuer, GR, AC, Arizona (National Aerosol Delivery Focusing on release as well as particle transport and deposition, two sequential tasks are necessary: (a)

NCSU Clement $473,748 $0 X ET, HE, OE Institutes of Health) Asthmatic Children prediction of the controlled air-particle conditions and optimal release parameters, employing 10/1/2009 9/30/2011 93.701 2009-2135 4/28/2009

The mechanisms that lead to the activation of procaspases play central roles in the regulation

of apoptosis and inflammation. For all procaspases, formation of a dimer is a critical event in

processing because the active sites of the enzyme are comprised of loops contributed by both

monomers of the dimer. However, a fundamental difference exists in the caspase subfamilies

regarding dimerization and maturation, and this difference is a key aspect for regulating

apoptosis. Several inflammatory and initiator procaspases exist as inactive monomers in the

cell, but the proteins have relatively high enzymatic activity upon dimerization. For those

caspases, chain cleavage simply stabilizes the active site. In contrast, the executioner

procaspase-3 is a stable dimer, but it has very little enzymatic activity. In this case, maturation

is dependent on cleavage by the initiator procaspases. Our long-term goals are to understand

how dimerization, activation and enzymatic activity are coupled for procaspases. Overall, we

want to determine why procaspases-1 and -8 are monomers, but yet the active sites form

National Institutes Dimerization Mechanisms of Two properly upon dimerization. In contrast, we want to determine why the stable dimer of

NCSU Clark, Allan C. $312,339 $0 X HE, OE of Health Procaspase Subfamilies procaspase-3 is not active. We hypothesize that the procaspase dimer exists in two primary 7/1/2002 12/31/2014 93.859 2002-0368 4/28/2009

Nanomaterials are promising materials for biomedical applications due to the exceptional

properties they exhibit, and this is particularly true for the use of carbon nanotubes (CNTs) as

prospective reinforcing elements in biomaterials. However, the uncertainty regarding the

cytotoxicity and genotoxicity of CNTs has hindered progress in their use for biomedical

applications. This research aims to reveal that CNTs when introduced into living organisms

through biodegradable medical devices are nontoxic resulting in no or negligible short term or

projected long term effects. These findings will subsequently validate CNTs safe utilization and

compatibility for several orthopedic applications. The specific aims of the proposed research

include 1) Histological assessment of the effect of CNTs-based biomaterials on animals?

connective tissue, epithelial tissue, and major organs (i.e liver, spleen, kidney), 2) Assessment

of the cytotoxic effects of CNTs-based biomaterials, and 3) In vivo characterization and

Texas Tech Short Term & Predictive Long Term documentation of the degradation behavior of CNTs-based biomaterials as a function of their

Marcellin-Little, University (National Response of Residual location in the body. Most studies so far have reported on basic findings conducted in vitro.

NCSU Denis J. $581,200 $0 X ET, HE, OE Institutes of Health) Nanomaterials in Living Organisms However, the in vivo animal testing being suggested in this research will provide a more 9/1/2009 8/31/2011 93.701 2009-2137 4/28/2009









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This application addresses broad Challenge Area (05) Comparative Effectiveness Research and

Specific Challenge Topic, 05-EY-101: Treatment of Age Related Macular Degeneration and

Diabetic Eye Diseases and Disorders. Diseases that exhibit retinal degeneration, such as age

related macular degeneration (aMD), have common themes of photoreceptor (rod and cone)

cell death. Sparing or delaying photoreceptor cell death is the main goal of treatment for age

related macular degeneration and other retinal degenerative diseases. This application will

test one such intervention for its ability to slow the progression of photoreceptor cell death in

animal models of macular degeneration and retinitis pigmentosa (RP). These animal models

will serve as examples for the broader application in retinal diseases such as aMD. Testing of

animal models is key for the ultimate application in people. Transgenic pigs exhibiting an

inherited juvenile form of macular degeneration (Stargardt-like macular dystrophy-3: STGD-3)

and those exhibiting a form of RP will be treated with a nutritional supplement, the omega-3

fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). DHA is a

Petters, Robert GR, AC, National Institutes polyunsaturated fatty acid (PUFA) that is a major component of cell membranes in the retina.

NCSU M. $643,724 $0 X ET, HE, OE of Health DHA and Retinal Degeneration PUFAs are decreased in diseases such as STGD-3 and RP that have common features of retinal 9/30/2009 9/29/2011 93.701 2009-2138 4/28/2009

K-12 schools across the nation are implementing or considering implementing various

curricula that use engineering. From high school curricula that are fairly comprehensive (i.e.

Project Lead the Way) to textbooks intended for middle or high school courses (i.e. Survey of

Engineering from Great Lakes Press) to elementary school after school clubs based on

activities from engineering societies and more comprehensive sets of activities (i.e.

Engineering is Elementary from the Museum of Science, Boston), enthusiam for engineering in

K-12 is increasing. These curricular activites have different foci from increasing technological

literacy to encouraging students to pursue engineering. Although those of us who are

engineers are enthusiatic about this trend, to date, there is only cursory assessment data

available to indicate the efficacy of any of these approaches to meeting their respective goals.

Consequently, there is no guarantee that the overall affect on the fields of engineering won?t

be negative, if these activities become nothing more than an educational ?fad.? Solid research

Do Engineering Curricula Improve on the abililty of engineering curricula to support solid student learning is needed. This

Bottomley, National Institutes Science and Mathematics Learning proposal describes a project designed to comprehensively assess student learning with an

NCSU Laura J $561,153 $0 X HE, OE of Health in Elementary School Students? elementary school curriculum (Engineering is Elementary) and a comprehensive 9/1/2009 8/31/2011 93.701 2009-2139 4/28/2009



Membrane proteins are important constituents of biological cells and currently constitute

over 50% of drug targets aimed at treating a broad spectrum of diseases including cancer,

schizophrenia, ulcers, HIV, and many others. Here, new solid-state Nuclear Magnetic

Membrane Protein Structures and Resonance (NMR) methodology will be developed for structure determination of membrane

Nevzorov, National Institutes Ligand-Induced Conformations By proteins, which will yield an atomic-resolution drug screening method for membrane proteins

NCSU Alexander A. $560,398 $0 X ET of Health Solid-State NMR in their native physiological environment. 9/30/2009 9/29/2011 93.701 2009-2140 4/28/2009

Issues relating to decision-making competence are of increasing interest in the field of

gerontology as the average lifespan increases, along with the number of older individuals who

are faced with important life decisions having to do with health care, finances, end-of-life

care, and housing. One focus of research in this realm is the assessment of the ability to both

comprehend and make decisions in people who may be experiencing initial stages of dementia

or whose health problems are in danger of impairing their mental abilities. It is also critical,

however, that we understand how judgment and decision-making processes in healthy older

adults are affected by factors associated with aging. Changes in our society have resulted in

these individuals being faced with increasingly complex choices in a wide-variety of domains

with important implications for physical and financial well-being, and continued

independence. It is also the case that as families become more widely dispersed and the rate

of technological change accelerates, older adults may be faced with making decisions without

Hess, Thomas National Institutes adequate social and knowledge-based supports. Finally, older adults are increasingly and

NCSU M. $350,075 $0 X ET, HE, OE of Health Social Cognition and Aging disproportionately targeted for marketing scams. Thus, it is important to understand the 1/1/2009 12/31/2013 93.701 2008-2455 4/28/2009









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QUANTITATION AND OPTIMIZATION OF DRUG AND NANOTHERAPEUTICS DELIVERY INTO SKIN

This application addresses broad Challenge Area (15) Translational Science, 15-AR-106:

Transdermal Drug Delivery. The goal of this research is to identify and quantitate those

physicochemical properties of small molecules and nanomedicines that result in significant

skin penetration while not being appreciably absorbed into the blood circulation. We have

identified the knowledge gap and opportunity in drug delivery for skin targeting of small

molecules and nanomedicines. Conventional transdermal drug delivery research focuses on

systemic absorption, yet systemic delivery is not required for many skin diseases including skin

cancer (melanoma, squamous and basal cell carcinoma) and other chronic diseases. At

present, there is no quantitative approach for skin targeted delivery of small drugs and

nanomedicines. We have developed a quantitative structure permeability relationship (QSPeR)

for quantitative assessment of diverse chemicals in complex chemical mixtures, which is

Quantitation and Optimization of applicable to transdermal delivery from realistic clinical formulations. Our approach is based

National Institutes Drug and Nanotherapeutics on using an isolated perfused skin model previously validated for predicting human drug

NCSU Riviere, Jim E. $999,982 $0 X HE, OE of Health Delivery into Skin delivery. This model contains all biological functions of viable skin, making it superior to 10/1/2009 9/30/2011 93.701 2009-2147 4/28/2009

This application addresses broad challenge area (03) Biomarker Discovery and Validation.

Challenge topic 03-AI-101 -- Identification, characterization and evaluation of novel pathogen

or host targets that may lead to the development of antimicrobials with broad spectrum

activity. It is the goal of this research to identify virus components which are essential for

replication of arthropod bourne viruses (Arboviruses) in mammalian cells but not insect cells.

This research will identify targets for production of vaccines and antiviral agents against many

of the 600-700 known agents in this class. Among these agents are dengue fever, West Nile

Fever, Chikungunya Fever Yellow Fever and many forms of viral encephalitis. This will be done

by random mutagenesis of the RNA of the model alphavirus Sindbis. Mutations produced will

be screened for ability to grow in mammalian and insect cells. Those which replicate efficiently

in insect but not mammalian cells will be further characterized by identifying the mutated

genes by complementation with a set of well characterized temperature sensitive (TS)

Hernandez, GR, AC, National Institutes New Targets for Production of mutants. The identified gene will be sequenced to determine changes in sequence and the

NCSU Raquel $447,000 $0 X HE, OE of Health Arbovirus Vaccines and Antivirals nature of any amino acid changes. The suspected mutation will be reproduced in the wild type 10/1/2009 9/30/2011 93.701 2009-2149 4/28/2009

Cancer cells typically have gained the ability to circumvent apoptosis, so the proteins in the

apoptotic cascades have become ideal targets for cancer therapy. Learning to selectively

manipulate the level of apoptosis is expected to provide new therapeutic strategies for the

treatment of cancer. As a proof of this principle, upstream components of the cascades have

been shown to be effective targets, but the therapy is most efficient only when combined to

target multiple proteins. Importantly, current cancer therapeutics activate caspase-3, albeit

indirectly. We have established that procaspase-3, the executioner of cell death, is a viable

target for therapy by showing that the activated zymogen is highly efficient in inducing

apoptosis in mammalian cells. One advantage of directly activating procaspase-3 is that the

polypeptide chain is not cleaved, which may circumvent the endogenous inhibitor XIAP. In

addition, procaspase-3 is the terminal protease in apoptosis, so it is unlikely that cells need to

be sensitized in combined therapies. Once procaspase-3 is activated, the cell dies rapidly by

GR, AC, National Institutes Crystallographic Studies of apoptosis. Under normal conditions, procaspase-3 has very little enzymatic activity until the

NCSU Clark, Allan C. $496,631 $0 X HE, OE of Health Constitutively Active Procaspase-3 polypeptide chain is cleaved by initiator caspases, but structural data are lacking to explain the 10/1/2009 9/30/2011 93.701 2009-2152 4/28/2009









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This project uses a series of data gathering and testing activities to separate unique issues

associated with biotechnology, tissue engineering, nanomedicine, and synthetic biology from

common issues associated with all technologies. Stakeholders involved in these four fields

have significant differences in their levels of understanding. While it may not be necessary for

public communities to have to same level of technical expertise as technical communities, a

baseline must be set for meaningful dialogues. As such we have designed a project that moves

step by step through a fact and opinion gathering process beginning with experts in research

communities to experts in regulation and media to a broad set of stakeholders known as the

public. This call creates some challenges. For example, the emergent nature of these

technologies may present special ethical concerns. As technologies converge and new

applications surface the ethical issues can evolve. Nanomedicine raises ethical concerns

regarding monitoring that takes privacy interest to another level. At other times, we see a

Berube, David National Institutes Emerging Technologies, Societal natural progression of ethical issues, such as how biotechnology through synthetic biology

NCSU M. $671,950 $0 X HE of Health Implications, and Publics impacts human hubris challenging religious beliefs. Another challenge involves how to affect 1/1/2010 12/31/2011 93.701 2009-2159 4/29/2009

NIH - 09-ES-101 Building trust between researchers and communities through capacity

building in Environmental Public Health - Environmental Public Health, Organizational Trust

and Public Communities. Given the complexity of the environmental public health and the high

levels of uncertainty associated with it, deference to researchers as experts is a default.

However, if experts are to entertain high levels of efficacy demands correspondingly high

levels of organizational trust. Researchers function as individuals and as a research

community. They seldom communicate directly with public communities. When they speak to

the media, regulators and policy makers, they speak for their field hence they function as

communities or organizations more than as individuals per se. Indeed, the public perceives

them as speaking as a community. Trust in communities and organizations by individuals and

other communities or organizations while sharing some similarity to interpersonal and

relational trust remains a distinct area of scholarship. Understanding how to best capture,

Environmental Public Health, maintain, or increase trust capacity between research and public communities demands a

Berube, David National Institutes Organizational Trust, and Public different set of exercises and activities than one would undertake during a team-building

NCSU M. $745,718 $0 X HE, OE of Health Communities workshop at a corporate retreat. As such we offer a project with a series of building blocks. 1/1/2010 12/31/2011 93.701 2009-2160 4/29/2009



The Post Doctoral Associate supported by the Administrative Supplement will will work with

the graduate student currently funded on the project to optimize acoustic parameters for

activation of stealth agents; and will then will lead the integration of the custom ultrasound

transducer designed as part of this project with the Visualsonics ultrasound system. This will

require fabricating electronics, software programming, testing, and calibration. The Post

Columbia University Immune-Shielded, Ultrasound- Doctoral Associate will also be the lead person on the animal imaging studies to evaluate in

(National Institutes Stimulated Contrast Agents for vivo performance of the improved ultrasound molecular imaging technology by using

NCSU Dayton, Paul A. $148,970 $0 X HE, OE of Health) Molecular Imaging conventional rodent models of angiogenesis. 9/30/2008 12/31/2012 93701 2008-1247 4/29/2009

The objective of this proposed research is to develop a novel surface-enhanced Raman

scattering (SERS) system based on plasmonics-active nanowire biochips for biomedical

diagnostics, more specifically for early diagnosis of cancers (breast cancer, prostate cancer,

and colon cancer). The introduction of molecular gene signatures in these types of cancers

provides important prognostic and predictive information, and holds promise for

individualized molecular therapy of these patients. In this project we propose wafer-scale

development of molecular sentinels-on-chip for detection of several unlabeled candidate gene

biomarkers known to play a critical role in the different cancers mentioned above. We

propose the reproducible development of plasmonics-active substrates having controlled sub-

5 nm gap between metal-coated nanowire structures over an entire 6-inch wafer from which

the SERS biochips will be obtained. Our methodology employs a hybrid approach integrating a

top-down technique using deep UV lithography with a bottom-up method based on controlled

Duke University Plasmonics-active Nanowire epitaxial growth of silicon germanium on silicon nanostructures to form diamond-shaped

GR, AC, (National Institutes Structures on Chip Platforms for nanowire structures that are coated with a metallic layer to form a plasmonics-active

NCSU Misra, Veena $150,000 $0 X ET, HE, OE of Health) Biomedical Diagnostics substrate. This unique methodology provides the scaling process for bridging the gap between 9/1/2009 8/31/2011 93.701 2009-2161 4/29/2009









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Preliminary Notice, Proposals and Awards





Rapid advances in nanotechnology will be accompanied by the exposure of millions of

individuals to products containing nanomaterials. Carbon Nanotubes (CNTs) are engineered

nanomaterials designed for multiple uses (electronics, engineering, medicine), but have

properties similar to asbestos, a fiber that is linked with the development of pulmonary

fibrosis (tissue scarring) and mesothelioma (a rare cancer on the pleural surface of the lung).

We found that mice which inhaled CNTs have increased platelet-derived growth factor (PDGF)

and monocyte chemotactic protein-1 (MCP-1), two important mediators of fibrosis and pleural

disease. We also found that CNTs activate the tumor suppressor p53, which is implicated in

mesothelioma. The broad challenge area addressed is ?13: Smart Biomaterials ?

Theranostics?. The specific challenge area is ?Methods to evaluate the health and safety of

nanomaterials: 13-ES-101?. The challenge to our laboratory is to determine whether CNTs

inhaled into the lungs of mice cause pathologic effects similar to asbestos fibers and to

The Challenge of Determining explore the mechanisms through which CNTs activate specific cell signaling events linked to

Bonner, James GR, AC, National Institutes Whether Carbon Nanotubes the progression of fibrosis and/or cancer. The specific hypothesis to be tested in this proposal

NCSU C $962,797 $0 X ET, HE, OE of Health Represent the Next Asbestos is that CNTs activate growth factor and chemokine signaling pathways that act coordinately 10/1/2009 9/30/2011 93.701 2009-2162 4/29/2009



The flip side to all the useful applications of nanotechnology is that toxic nanomaterial is being

inhaled during nanoparticle generation, micro-device fabrication, material handling and

product use. The proposed work involves support from experts in experimental toxicology,

pulmonary radiology, petascale computing science, and biomedical/mechanical engineering.

Computational Evaluation of The anticipated results link realistic ambient nanoparticle concentrations with inhaled

Kleinstreuer, GR, AC, National Institutes Inhaled Nanomaterial Deposition in deposition data sets, which are of interest to toxicologists, epidemiologists, health-care

NCSU Clement $912,364 $0 X ET, HE, OE of Health Subject-specific Lung Airways providers and federal regulators alike. 10/1/2009 9/30/2011 93.701 2009-2163 4/29/2009

The concepts of hot carriers and carrier multiplication (CM) in quantum dot (QD) structures

have been demonstrated using spectroscopic techniques. However for photovoltaic

applications, collecting these carriers is a major challenge and was not yet demonstrated.

When QD are configured to allow charge extraction (type I interfaces), new non-radiative

recombination channels are opened that arise from charge delocalization and increased

surface trapping and recombination sites. Also, the time scales for charge separation and

charge transport should be fast compared to carrier cooling and carrier recombination. Our

approach addresses the above challenges by using well-developed lattice matched epitaxial

heterostructures incorporating both type I and type II band line up interfaces for fast carrier

extraction. III-V compounds offer the required flexibilities to address these issues and allow

optical absorption to take place in the QD only. Our experience with Atomic Layer Epitaxy

Extraction of Hot and Multiple (ALE) will allow more effective passivation of these QDs. We will focus our investigation on

Bedair, Salah GR, AC, Exciton Generated Carriers in InAs QDs because the band mass of holes is significantly higher than that of electrons, thus

NCSU M. $2,130,842 $0 X ET, HE, OE US Dept. of Energy Quantum Dot Structures. enhancing the phonon bottleneck and allowing low minimum photon energy for CM. 11/1/2009 10/31/2012 81.049 2009-2165 4/29/2009

Joint degenerative diseases such as osteoarthritis (OA) can be severely debilitating conditions.

The end stages of this disease process are fairly well documented but, the early degenerative

changes are poorly understood and biomarkers that indicate the initiation of the disease and

severity of the disease are unknown. While most cases of joint degeneration are idiopathic in

nature, joint injury is a known predisposing factor. Joint degenerative diseases involve all of

the joint tissues, bone, cartilage and synovium; however, the articular cartilage is the most

significantly affected tissue and tends to see the most damage. Cartilage degeneration is likely

to be a very complex process involving the chondrocytes that are responsible for the

maintenance and health of the tissue and the extracellular matrix that controls the mechanical

environment for the cells and allows for the transmittal of loads and smooth motion of the

Identification of Potential joint. The response to injury will require changes in the chondrocyte phenotype as the cells

Biomarkers Associated With respond and adapt to the new and changing environment post injury. Understanding the

National Institutes Persistent Cartilage Damage After chondrocyte phenotypic changes that occur post injury are a first step in unraveling the

NCSU Mente, Peter L. $1,000,000 $0 X HE, OE of Health an In Vitro Impact Injury changing cell processes. Because of the long time frame over which OA develops transient 10/1/2009 9/30/2011 93.701 2009-2168 4/29/2009









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The overall research goal of our multi-disciplinary research team at North Carolina State

University is to define novel microbial targets to overcome antibiotic resistance. This approach

allows us to define alternative therapeutic approaches that will work synergistically with

conventional antibiotics to control and eliminate multi-drug resistant infections. The two

applications that we focus on are: 1) control of bacterial biofilm development/maintenance

and 2) suppression of antibiotic resistance genes. The reason for focusing on these two

aspects of bacterial behavior is straightforward. First, 3 in 4 bacterial infections are biofilm-

based. Bacteria within a biofilm are known to be upwards of 1000-fold more resistant to

antibiotics and are inherently insensitive to the host immune response. Thus, bacteria in a

biofilm represent a significant hurdle for antibiotic treatment. Second, the dissemination of

antibiotic resistance genes amongst diverse pathogenic bacteria coupled with the dearth of

new antibiotics that have been introduced by the biomedical community has led to a situation

GR, AC, National Institutes Isolation of Novel Targets to in which many microbial infections are multi-drug resistant and extremely difficult/impossible

NCSU Cavanagh, John $997,778 $0 X ET, HE, OE of Health Remediate Vibrio Infections to treat. We have developed a lead compound that will inhibit and disperse biofilms across 9/30/2009 9/29/2011 93.701 2009-2178 4/29/2009

This project took longer time than that of originally expected due to two major reasons. First,

hiring all qualified personnels took 2 years because this is a new investigator?s project.

Second, The project leads an unexpected and physiologically important finding as described

below. Therefore, the project requires additional support. The original specific aims are; 1) to

determine the role of TAK1 in TGF-b signaling; 2) to isolate and characterize

scaffold/regulatroy molecules associated with TAK1; 3) To create and characterize mice with a

skin specific deletion of TAK1. We have completed Aim 1 and have determined the roles of

several TAK1 binding proteins (Aim2); however, characterization of TAB1 and TAB2, which are

constitutive binding partners of TAK1, are currently in progress. Results in Aim 1 and Aim 2

indicated that TAK1 is an essential signaling molecule to induce inflammatory responses.

However, to our suppress, we discovered that TAK1 deletion causes skin inflammation in Aim

3. TAK1 is essential not for inducing but for preventing inflammation in an in vivo setting. This

unexpected finding raised questions that have to be addressed in Aim 3 more than we

National Institutes TAK1 Regulation of TGF-beta and IL- originally anticipated. We are currently attempting to define the molecular mechanism by

NCSU Tsuji, Jun N. $83,140 $0 X ET, HE, OE of Health 1 Signaling which TAK1-deficiency causes inflammation. We have found that TAK1 is essential for reactive 3/1/2004 3/31/2014 93.701 2003-1966 4/29/2009



UNC - UNC Chapel This is to increase the subcontract to NCSU in order to obtain a Bio-Rad Bio-Plex 200 system to

Threadgill, GR, AC, Hill (National Systems Genetics Research run cytokine and adipokine analyses on the Collaborative Cross mice as part of the Systems

NCSU David $66,298 $0 X HE, OE Institutes of Health) Consortium Genetics Reource Consortium. 10/1/2008 8/31/2012 93.701 2009-0725 4/29/2009

It is apparent that MARCKS protein is a major signaling molecule in a variety of cellular

functions. In the lung, MARCKS serves as a crossbridge between stimulation at the cell surface

and subsequent secretion of mucin from epithelial secretory cells. MARCKS also can serve as a

mediator of leukocyte degranulation as well as leukocyte migration, suggesting it also has an

important role in inflammation. One of the key findings of the previous funding period is that

it appears to be the N-terminus of MARCKS that is involved in these functions, as a peptide

identical to the MARCKS N-terminus has potent effects on these parameters when cells are

treated with it. The studies in the next funding period will now investigate and further nail

down the exact molecular mechanism(s) by which MARCKS interacts with other cellular

proteins in each of these cell types in order to carry out its function. We will use some new

imaging techniques as well as develop new methods to assay for secretion and epithelial

function. We plan to use proteomic approaches to identify novel proteins associated with

Adler, Kenneth National Institutes Mechanism of Oxident-Induced mucin granule membranes and investigate their interactions with MARCKS during the

NCSU B. $28,425 $0 X HE, OE of Health Respiratory Mucin Secretion secretory process. We also plan to expand our collaborations with investigators at Duke 4/1/1987 2/28/2014 93.213 1987-1036 4/29/2009









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The aim of this work is to design theranostic liposomes for targeting solid tumors that can be

programmed to simultaneously release a chemotherapeutic agent (doxorubicin) and an

imaging agent. The goal is to maximize the therapeutic index (killing efficacy) per delivered

drug, thus administering lower drug doses to the patient, and reducing toxicities. Concurrent

release of radioactive imaging agents will allow physicians to monitor the effectiveness of the

treatment and the spread of metastatic cells. These goals will be accomplished through a

combined experimental and theoretical approach which optimizes the design of liposomes

formed by combining two different functionalized lipids. The first lipid, DSPS will be

functionalized with PEG tethered to an antibody that targets PSMA on the surface of cancer

cells. The second lipid, 21PC, will be functionalized with a fusion peptide that promotes fusion

Polytechnic with the endosomal membrane. At normal pH, the two different lipids will be uniformly

Institute of NYU Design of Multifunctional Doubly- distributed across the liposome surface with the PEG tails hiding the fusion antibodies because

GR, AC, (National Institutes Fusogenic Liposomes For DSPC is negatively charged at these conditions. At low pH, which is characteristic of the tumor

NCSU Hall, Carol K. $350,000 $0 X ET, HE, OE of Health) Theranostic Applications vasculature, the liposome membrane will phase separate into two domains because DSPC 10/1/2009 9/30/2011 93.395 2009-2182 4/29/2009

The ability to identify and characterize protein interactions has a broad impact in all areas of

health-related research, and thus methods related to their identification and characterization

are important for understanding disease pathogenesis. By elucidating how proteins interact, a

fundamental understanding of their biochemical properties begin to emerge, which can lead

to a better understanding of the underlying mechanisms of protein function. Although NMR or

x-ray crystallography provide the gold standard for high resolution structural detail, these

techniques do not easily lend themselves to the study protein dynamics in dilute aqueous

solutions and are not amenable to the study of large macromolecular complexes comprised of

many proteins isolated from cells or clinical samples. The overall research goal of our multi-

disciplinary research team is to develop a new mass spectrometry approach termed XID-MS.

XID-MS: A Novel Integrated Mass This method integrates recent advances in chemical crosslinking (CXL) reagents, ion mobility

Spectrometry Approach to mass spectrometry (IMMS), and data-independent acquisition (DIA) mass spectrometry (MS)

Structurally Characterize Protein analysis. This XID-MS approach utilizes unique gas phase-based separations and selective low-

Goshe, Michael National Institutes Oligomerization and Mega- energy fragmentation events to enable protein components within mega-macromolecular

NCSU B. $999,653 $0 X ET, HE, OE of Health Macromolecular Complexes complexes (> 200 proteins) to be quantitatively identified while simultaneously providing 10/1/2009 9/30/2011 93.701 2009-2186 4/29/2009

Environmental toxins, such as the herbicide paraquat, cause neuronal cell death through

oxidative stress. Locomotor impairments are sensitive indicators of neurodegeneration. A long-

standing challenge in environmental health science is to assess the effects of environmental

chemicals such as pesticides or herbicides on genetic risk for neurodegenerative diseases as

manifest through locomotor dysfunction (e.g. Parkinson?s disease). Studies on genotype by

environment interactions require a model system in which both the genetic background and

the rearing environment can be controlled precisely. The fruit fly, Drosophila melanogaster,

provides such a model. In this application we propose to capitalize on natural variation in

inbred wild-derived strains of Drosophila to construct genome-wide networks of covariant

transcripts that are associated with a range of locomotor phenotypes, including spontaneous

activity, startle-induced locomotion, and gravitaxis, under control conditions and after chronic

exposure to paraquat at a concentration that is not acutely lethal, but shortens lifespan. In

addition we propose to associate DNA sequence variants in 192 inbred wild-derived

Anholt, Robert GR, AC, National Institutes Oxidative Stress and Neurogenetic Drosophila lines with fully sequenced genomes with variation in these behavioral phenotypes

NCSU R. $720,232 $0 X HE, OE of Health Networks in Drosophila under control conditions and after paraquat exposure. The combined information from these 10/1/2009 9/30/2011 93.701 2009-2191 4/29/2009









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A thorough analysis, for a defined four year period, will be undertaken to review opinions

from the U.S. Patent Board of Interferences & Appeals, the United Sates Court of Appeals for

the Federal Circuit, and the United Sates Supreme Court to determine the extent to which

groups or clusters of patents (commonly referred to as patent thickets) applicable to human

genome discoveries have been discussed and/or issued. Additional reviews, for the same time

period, will be undertaken to search law reviews and journals to ascertain emerging or

prevalent intellectual property principles used in human genome patent efforts together with

the identification of obstacles or barriers anticipated to encumber the utilization of such

patent discoveries in the medical diagnosis, treatment or research on behalf of patients. The

objectives of the planned research are to gauge intellectual property barriers to widespread

use of beneficial genome discoveries and to anticipate new constructs or legal principles likely

Impact of Intellectual Property to arise as genome-related technology accelerates and is more widely used in medicine.

Schanz, National Institutes Issues on Human Genome Specifically, research will examine the extent to which patent thickets have been used in the

NCSU Stephen $463,359 $0 X HE, OE of Health Diagnostic Patents patent issuance process. The cost-effective adoption of new technologies and advances is 1/1/2010 12/31/2011 93.701 2009-2195 4/29/2009

Osseointegrated prosthetics can potentially replace the external prosthetics currently used by

most amputees. Instead of having a loose socket that is fit over the stump the osseointegrated

prosthetics are attached to the bone in the stump surgically and a part of the implant is

breaking the skin barrier. A prosthetic limb can then be attached to the implant once the bone

has grown into the implant and providing a stable fixation. The osseointegrated prosthetics

can resolve many of the current issues with the external prosthetics and provide a better

solution for patients that would like to live an active life style despite their handicap.

Osseointegrated prosthetics have been design, fabricated and implanted by the research team

at NCSU using animals with amputated limbs with great success. The proposed research

project is aimed at laying the way for translating the technology into the human medicine. A

collaborative effort has been initiated with orthopedic surgeons at Duke Medical Center and

the Rehabilitation group at the Durham VA Medical Center. The proposed research will

Harrysson, Ola National Institutes Translational Research For develop custom osseointegrated prosthetics for 10 human amputees and mock surgeries will

NCSU L. $847,573 $0 X HE, OE of Health Osseointegrated Prosthetics be performed using leg replicas. Throughout the project the quality control and implant 10/1/2009 9/30/2011 93.701 2009-2218 4/29/2009

The general long-term objective of this project is to develop theories and statistical methods

to characterize and analyze the genetic architecture of quantitative traits and to learn the

genetic and evolutionary bases of quantitative trait variation within and between natural and

experimental populations. The specific goals of the current application are: (1) Use a score

statistics based re-sampling method to assess the relevant criterion for model selection under

multiple interval mapping for mapping multiple QTL. Develop and assess a procedure to

analyze QTL epistasis under multiple interval mapping. (2) Extend MIM to multiple traits in

multiple environments and populations (MT-MIM) to combine data for QTL analysis, to study

genetic basis of trait correlations and genotype by environment interaction. Specific research

includes formulation and implementation of efficient model selection procedures, assessing

appropriate model selection criterion, implementation of procedures for testing a number of

biologically interesting hypotheses, such as pleiotropy vs. close linkage. (3) Further develop

Statistical Methods For Analyzing and update QTL Cartographer and Windows QTL Cartographer. This includes adding new

Zeng, Zhao- GR, AC, National Institutes the Genetic Architecture of features to the software, constantly updating functions, features and interface of the

NCSU Bang $553,032 $0 X ET, HE, OE of Health Complex Traits software; and maintaining the interaction with users. The new features include various 9/30/2009 9/29/2011 93.701 2009-2197 4/29/2009









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This proposal is in direct response to Challenge Area (12): Science Technology Engineering and

Mathematics Education (STEM), RFA 12-OD-105 Identification of practices that overcome

equity issues in STEM learning. Encouraging diversity within the population of students

interested in STEM careers. Efficacy and effectiveness of specific approaches that aim to

increase diversity in the STEM workforce. This project plan introduces and evaluates a novel

toolkit and program designed to capture and sustain the interest and enthusiasm for science

and discovery of students in Alaska Native or American Indian communities. In this program,

local teachers (and their students) are provided with straightforward, logical and illustrative

field deployable portable assays known as Screens to Nature (STN) technology, and thoroughly

coached on the use of these renewable and extremely safe to use testkits to investigate the

biological activity of indigenous plants, fungi, microbes and marine organisms in their

communities. The inventive STN portfolio is designed to help students recognize the unique

In-Field Biodiscovery Framework a bioactive (human health protective) properties of the local natural resources, to put the

GR, HE, National Institutes Catalyst for Science Education and students in direct charge of making novel discoveries taking advantage of the scientific

NCSU Lila, Mary Ann $978,564 $0 X EV, OE of Health Validation of Traditional Knowledge method, and to validate the traditional ecological knowledge of the community elders through 10/1/2009 9/30/2011 93.701 2009-2201 4/29/2009



Despite the great promise offered by game-based learning environments for middle school

science education, realizing its potential poses significant empirical challenges. In this project

we will conduct a controlled study to evaluate the effectiveness of an intelligent game-based

learning environment, Crystal Island, which leverages both commercial game technologies and

Crystal Island: Evaluating an the inferential capabilities of intelligent tutoring systems. The effectiveness of specific features

Intelligent Game-Based Learning of the Crystal Island intelligent game-based learning environment will be tested in a controlled

National Institutes Environment For Eighth Grade study with a population of eighth grade students. The subject matter focus will be the

NCSU Lester, James C. $999,064 $0 X ET of Health Microbiology standard eighth grade microbiology curriculum. 10/1/2009 9/30/2011 93.701 2009-2206 4/29/2009

Telomerase is the ribonucleoprotein complex responsible for synthesizing telomeric DNA at

the ends of chromosomes, thereby extending the proliferating capacity of the cell and

minimizing genomic instability. Approximately 90% of human cancers involve reactivation of

telomerase; thus, making telomerase an attractive target for cancer therapy, diagnosis, and

prognosis. Human telomerase is composed of an RNA (hTR), a reverse transcriptase protein,

and additional protein subunits. The hTR contains four conserved domains: (1) the pseudoknot

domain which provides the template and enhances repeat amplification processivity, (2) the

CR4/CR5 domain which supports the catalytic activity, (3) the H/ACA and (4) the CR7 domains

which are involved in localization, accumulation, and 3?? end processing. Very little is known

structurally about the telomerase complex, yet this knowledge and an understanding of the

molecular interactions between its RNA and protein components are essential to understand

its function and mechanism. The long term goal of this project is to understand structure-

Three Dimensional Structure function relationships in human telomerase with a special attention to the regulation of

Yingling, National Institutes Prediction and Analysis of telomerase activity, since telomerase inhibitors could be broadly effective cancer

NCSU Yaroslava $321,800 $0 X ET, HE, OE of Health Telomerase RNA therapeutics. Toward this goal, we propose to conduct structural, thermodynamic, and 9/30/2009 9/29/2011 93.701 2009-2208 4/29/2009

Some 30 million people are infected with human immunodeficiency virus. Existing anti-virals

target HIV protein functions. But, HIV is capable of mounting significant resistance to drug

intervention that targets proteins. Antiretroviral resistance develops when viral replication

continues in the presence of the selective pressure of drug exposure, especially when the

drugs are directed against the same or similar protein targets. Unfortunately, vaccine

development has been problematic. Novel targets for intervention are sought in which the

development of resistance will be difficult. The proposed approach changes the focus from

that on HIV proteins alone to the distinctive chemistry and structures of a unique target of

opportunity, HIV?s recruitment of the human tRNALys as the primer of reverse transcription.

All retroviruses use a host cell tRNA species as the primer for reverse transcription. HIV?s

steadfast dedication to the host tRNALys3 species as the primer validates the human tRNA

National Institute of recruitment by viral proteins as a possible target of intervention. This is a target that may

GR, AC, Allergy and HIV Infection: Early Events and New preclude drug resistance because of the central role of the tRNA in viral replication and in host

NCSU Agris, Paul F. $990,071 $0 X ET, HE, OE Infectious Diseases Targets of Intervention cell translation. The HIV proteins polymerase, Gag and nucleocapsid and the human lysyl-tRNA 9/1/2009 8/31/2011 93.701 2009-2212 4/29/2009









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Drug-induced liver injury (DILI) is the major adverse drug event that leads to regulatory actions

on drugs, including failure to approve, restricted indications, and withdrawal from the

marketplace. The most problematic form of DILI is ?idiosyncratic?, meaning the drug is safe

for the vast majority of treated patients while causing catastrophic liver injury in the rare

susceptible patient. A variety of data suggests that genetic factors may largely underlie

susceptibility, and there are now two gene banks established from patients who have

experienced DILI: The Severe Adverse Events Consortium (SAEC) and the Drug Induced Liver

Injury Network (DILIN) Genome-wide association studies and testing of specific hypotheses

based on drug metabolism and transport have met with limited success to date. What is

needed is an unbiased mechanism to generate specific hypotheses that can be tested in these

gene banks. We believe that a newly available mouse genetics resource, the Collaborative

Revolutionizing Preclinical Cross, may facilitate identification of rare alleles that contribute to idiosyncratic DILI. We

Detection of Risk Factors For hypothesize that drugs capable of causing idiosyncratic DILI in patients will produce DILI in a

Threadgill, GR, AC, National Institutes Idiosyncratic Drug-Induced Liver subset of the Collaborative Cross strains allowing detection of genes and pathways that

NCSU David $991,543 $0 X ET, HE, OE of Health Injury underlie DILI susceptibility in human patients. The proposed studies will test this hypothesis 9/30/2009 9/29/2011 93.701 2009-2213 4/29/2009



We propose herein a collaborative program between our two research groups with the

overarching goal of developing novel intracellular biosensors with prescribed properties for

live-cell imaging. The proposed project combines expertise in protein engineering (co-PI Rao),

live-cell imaging (PI Haugh), and quantitative cell biology (both labs). Our overall approach will

be to employ directed evolution of an ensemble of small (~ 10 kDa) protein scaffolds for

recognition of specific protein and lipid targets with relatively modest binding affinity (KD ~

Haugh, Jason National Institutes Novel Protein Biosensors For 0.1?10 �M); whereas most protein engineering efforts to date have sought tight, persistent

NCSU M. $975,163 $0 X ET, HE, OE of Health Imaging Intracellular Dynamics binders, those properties are entirely undesirable for intracellular biosensors. 1/1/2010 12/31/2011 93.701 2009-2215 4/29/2009

Bacterial drug resistance is an increasingly significant threat to the successful treatment of

infectious diseases. As antibiotic resistance continues to evolve, some pathogens that were

once considered routine to treat are developing, or have developed, resistance to almost

every antibacterial agent currently available. Furthermore, because infections caused by

resistant pathogens are associated with higher morbidity and mortality than those caused by

susceptible pathogens, the global impact of increasing resistance is a major concern. Given the

frequency with which gram-positive bacteria [Bacillus, Bifidobacterium, Corynebacterium,

Clostridium, (vancomycin-resistant) Enterococcus (VRE), Erysipelothrix, Listeria, Nocardia,

(multi-resistant) Staphylococcus aureus (MRSA), Streptococcus] are responsible for serious

nosocomial infections, it is no surprise that the emergence of resistance among these

organisms to existing antibiotics has become a serious medical issue in hospital settings, and

National Institute of Characterization and Evaluation of now emerging as community acquired resistance. Only two new classes of antibiotics have

GR, AC, Allergy and Novel Targets of Intervention in been developed and brought to market in decades. Corporate and academic researchers in

NCSU Agris, Paul F. $957,291 $0 X HE, OE Infectious Diseases Gram Positive Pathogens the field of antibacterial drugs, and antibiotic resistance have traditionally looked toward 10/1/2009 9/30/2011 93.701 2009-2217 4/29/2009

The extent of dermal absorption after topical exposure to manufactured nanomaterials under

different conditions is unknown. The focus of this research is to assess the effect of species,

vehicle and skin barrier damage on the dermal absorption or penetration of topically applied

model nanomaterials. Recent data suggests that specific vehicles may enhance nanomaterial

absorption in human skin. These studies will utilize carbon fullerenes and silver nanoparticles,

and cadmium selenide nanocrystals (quantum dots-QD) in human, rodent and porcine skin

using in vitro flow-through diffusion cell systems. The hypotheses to be tested are: I. Species

differences in anatomy and biochemistry will affect dermal disposition of nanomaterials,

specifically in the characteristics of the rate-limiting penetration barrier. II. Vehicle effects that

are primary determinants of chemical partitioning will also affect nanomaterials movement

into skin and must be controlled to make rational interpretation across different studies. III.

Effects of Species, Vehicle and Skin Alterations in skin function, such as would occur with UV irradiation (sunburn) or barrier

Monteiro, National Institutes Damage on Dermal Penetration of disruption to the stratum corneum, will modify nanomaterials penetration. These studies will

NCSU Nancy A. $999,423 $0 X HE, OE of Health Nanomaterial define those properties of skin that modulate nanomaterial absorption. All nanoparticles will 10/1/2009 9/30/2011 93.701 2009-2221 4/29/2009









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A large proportion of cancer patients develop also uncontrolled liver tumors which are then

the actual cause of death. Traditional treatment options of liver tumors range from surgery

(within early stages), via chemotherapy, to whole-body radiation. The latter two are

associated with severe side-effects. Furthermore, as effective as chemotherapy agents and

anti-angiogenic drugs may be, more than 50% of patients with solid tumors experience full

resistance to chemotherapy. Exclusively localized radiation via Y90-microspheres of

unresectable liver malignancies would be an effective and safe form of treatment. This could

be accomplished on a patient-specific basis with a smart micro-catheter which will allow for

Patient-specific optimally targeted delivery of radioactive microspheres. Steady 3-D fluid-particle dynamics

Computational/Clinical Particle- simulations (Kleinstreuer 2006) have demonstrated that the new methodology of optimal

Hemodynamics and Micro-Catheter targeting lung tumors (Kleinstreuer et al., 2008) also works in principle for targeting liver

Analyses for Targeted Delivery of tumors (Kennedy et al., 2009a, b). However, the rheology of blood-microsphere dynamics, the

Kleinstreuer, GR, AC, National Institutes Radioactive Microspheres onto presence of a (well-designed) micro-catheter, the internal microfluidics of the novel catheter

NCSU Clement $737,660 $0 X ET, HE, OE of Health Liver Tumors and its positioning in the hepatic artery for optimal microsphere release have to be 10/1/2009 9/30/2011 93.701 2009-2222 4/29/2009

ABSTRACT This application addresses broad challenge area (01) Behavior, Behavioral Change,

and Prevention and specific Challenge Topic, 01-CA-102: The Role of Nutrition in Cancer

Biology. Iron is an indispensable element in a variety of cellular functions including cell

proliferation. Cancer cells typically have increased iron requirements due to their high growth

and proliferation rates. In fact, cancer cells take advantage of higher availability of intracellular

iron for their rapid cell proliferation. However, little is known about the mechanism through

which cancer cells create the higher availability of iron. Is there a particular gene involved in

determining iron availability in cancer cells? We have recently found that ATF1 transcription

factor shows upregulation of transferrin receptor 1 and downregulation of ferritin H, resulting

in higher iron transport and lower iron storage. Increased ATF1 expression is responsible for

enhanced growth potential of some cancer cells including lymphomas and metastatic

melanoma cells. Furthermore, chromosomal translocation t(12;22)(q13;12) results in the

GR, AC, National Institutes Regulation of Iron Transport and fusion of the Ewings sarcoma oncogene (EWS) to ATF1 (EWS/ATF1) that functions through the

NCSU Tsuji, Yoshiaki $936,491 $0 X ET, HE, OE of Health Storage by Oncogenes ATF1 DNA binding domain and causes clear cell sarcoma and malignant melanoma of soft 10/1/2009 9/30/2011 93.701 2009-2224 4/29/2009





Recognizing patterns in complex data produced by diagnostic tests and other healthcare

processes is a common problem. It is especially challenging when the problem is not only one

of recognition but of discovering the pattern in the first place - and indeed of detecting if a

pattern to match a given desired decision exists in the data, for example when a new

diagnostic method is being investigated for suitability as replacement of an existing one.

Automated machine learning paradigms such as artificial life class of algorithms have been

suggested as suitable for this type of application, but such tools do not handle distributed

learning well. We hypothesize that a general automated learning system which consists of a

A Distributed General Automated perceptron learning machine replicated at diverse locations can be programmed to exchange

Learning and Knowledge learning data over a computer network, and serve as a powerful information technological

National Institutes Generation Tool For Diagnostic and tool for the development of new diagnostic methods. We propose research to design and

NCSU Dutta, Rudra $548,167 $0 X HE of Health Other Healthcare Data build such a system, and develop algorithms for the distributed learning ability. 10/1/2009 9/30/2011 93.701 2009-2231 4/30/2009









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Presently, early oxidative stress response biomarkers are not available and we have no way of

knowing whether an individual is under oxidative stress, which is a risk factor for development

of some diseases, including atherosclerosis. Mouse and rat models have answered many

questions about the biology of the oxidative stress response and will continue to be valuable

resources for researchers investigating redox imbalances. Rodent models, however, may not

be the best model system for discovering oxidative stress response biomarkers in humans.

Atherosclerosis does not lead to a myocardial infarction in mice. Also, the tunica media of the

mouse has less smooth muscle cells than humans, allowing atherosclerotic lesions to cross the

internal elastic lamina in these mice models. The pig is biologically more similar to humans

than the rodent; for example, the lipoprotein profile of the pig is more similar to humans and

pigs and humans have higher amounts of cholesterol than mice. Therefore, the pig has natural

advantages over the mouse as a biomedical model for human disease. Our experimental

Ashwell, South Dakota State Discovery of Oxidative Stress design should capture early biomarkers associated with oxidative stress and atherosclerosis.

Melissa GR, AC, University (National Biomarkers in a Pig Model of Oxidative stress biomarkers discovered by our study will be useful to researchers studying

NCSU Schuster $59,600 $0 X HE, OE Institutes of Health) Artherosclerosis diseases associated with an oxidative stress response. We anticipate that some biomarkers we 9/30/2009 9/29/2011 93.701 2009-2232 4/30/2009



This project will evaluate the utility of current peer review practices in radiation oncology,

with the aim of using this information to develop tools that support moving peer-review from

a retrospective to a prospective activity. The traditional peer-review quality assurance (QA)

methodologies used in complex radiation oncology have been based on physical, ?traditional-

paper? medicals record and physical film radiographs. As radiation oncology evolves toward

an entirely digital system (electronic medical records and digital images) the traditional QA

Development of a Simple Peer- methods need to be re-evaluated. The need to refine our QA procedures is imperative as

UNC - UNC Chapel Review Tracking Tool to Improve evolving radiation techniques become increasingly complex, thereby increasing the risk of

Mazur, Lukasz Hill (National Patient Safety in Clinical Radiation medical errors. The goal of this project is improve patient and community health by

NCSU M $194,859 $0 X HE Institutes of Health) Oncology decreasing medical errors in clinical radiation oncology. 10/1/2009 9/30/2011 93.701 2009-2235 4/30/2009

Elucidation of the structural events occurring within viruses as infection takes place is a major

goal of molecular and structural biology. The overarching goal of this research is to investigate

the structural changes in Sindbis virus which occur during the process of cell infection in a

series of Small Angle Neutron Scattering and X-ray crystallography experiments. Small-angle

neutron scattering with contrast variation is a powerful tool to gain molecular level structural

information of large, nested, multi-density, and spherical systems such as virus particles in

solution. Used in combination of contrast variation techniques, small angle neutron scattering

makes it possible to highlight different structural elements, thereby understanding the

assembly of the whole particle. It is the objective of this work to reproduce in vitro pH driven

conformational changes in Sindbis virus particles to mimic and characterize the structural

Analysis of the Structure and rearrangements that occur upon activation and infection process. X-ray crystallography will be

Function of a Model Alphavirus By used to acquire complementary atomic level information of the fusion peptide. Sindbis virus is

GR, AC, National Institutes Neutron Scattering and X-Ray a member of the Arbovirus group, a group of structurally unique infectious agents that are

NCSU Meilleur, Flora $933,371 $0 X ET, HE, OE of Health Crystallography transmitted by blood-sucking insects and produce some of the most devastating infectious 10/1/2009 9/30/2011 93.701 2009-2236 4/30/2009

Nearly all cellular functions are governed by proteins which mediate their biological specificity

by high affinity three-dimensional recognition. Thus, characterizing how proteins interact is

fundamental to understanding their biochemical properties as well as aberrant protein

function and manifestations of disease. Although many methods are available to study protein

interactions, most techniques are limited by some type of analytical restriction which

precludes the analysis of certain protein classes or higher order complexes. The overall

research goal of our multi-disciplinary research team is to develop a new approach using in-

solution chemical crosslinking and quantitative mass spectrometry analysis to characterize

protein complexes and macromolecular assemblies in their native environment. This will

involve synthesizing a series of chemical crosslinking reagents containing a specially designed

Novel Chemical CID-Crosslinking linker region that can be selectively fragmented upon collision-induced dissociation (CID) and

Reagents and Methods to Study be used to provide enhanced detection of modified proteins and complexes using liquid

Goshe, Michael GR, AC, National Institutes Biological Interactions of Proteins chromatography-tandem mass spectrometry (LC/MS/MS) analysis that cannot be achieved

NCSU B. $550,148 $0 X ET, HE, OE of Health Using LC/MS/MS Analysis with traditional crosslinking reagents. The modular design of these reagents will permit the 10/1/2009 9/30/2011 93.701 2009-2237 4/30/2009









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UNC - UNC Chapel

Tonkonogy, Hill (National Center for Gastrointestinal Biology

NCSU Susan L. $53,000 $0 X HE, OE Institutes of Health) and Disease This request is for funds to purchase an autoclave. 12/1/2007 11/30/2010 93.866 2008-1740 4/30/2009

Molecular recognition is central to biology, forming the foundation for precise hormonal

control of distant organs, immune targeting of nonself proteins, the specificity of enzymatic

catalysis, and exogenous control of biological systems. Many medications and biological

probes act by binding and usually inhibiting a specific macromolecular target. Indeed, the

discovery of a ligand that binds a targeted protein with high affinity is a major goal in the early-

stage drug discovery. However, discovering a small molecule that binds a specific protein

tightly, while retaining favorable pharmacological properties, can be a major challenge. In this

proposal, we intend to address one specific issue to overcome this challenge: how to

accurately describe the interactions with high enough efficiency to positively impact the

prediction of protein-ligand binding. Specifically, we propose the following. Aim 1: We propose

University of to develop a continuum polarizable force field for general organic molecules, based on the

California - Irvine recently developed continuum polarization framework for proteins for more accurate

(National Institutes High Accuracy Energy Models for treatment of polar interactions. Aim 2: We propose to develop a high accuracy finite-

NCSU Li, Zhilin $178,800 $0 X HE, OE of Health) Molecular Recognition difference Poisson-Boltzmann solver that allows coarse grid spacing to be used for high 9/30/2009 8/30/2011 93.701 2009-2259 4/30/2009

The proposed project will develop and surgically evaluate a novel device that will allow safe,

rapid and complete LAA occlusion through the use of shape memory alloy (SMA) tendons. An

estimated 2.3 million Americans have been diagnosed with atrial fibrillation (AF). Risk of

embolic stroke, resulting from increased production of thrombi in the LAA, is one of the most

severe potential outcomes of the arrhythmia. Occlusion or elimination of the LAA alleviates

stroke risk by preventing the release of thrombi from the appendage. The proposed device will

provide long LAA occlusion in the following settings: cardiac surgeries, minimally invasive

(thoracoscopic) epicardial ablation, as well as stand-alone LAA occlusion procedures. Perhaps

its greatest impact will be realized by patients with lone AF due to current procedural risks and

invasiveness of surgery. A reduction in complications (tissue bleeding, tearing) and increased

long-term reliability of closure, provided by the clip, could dramatically increase the number of

Virtual Environment to Develop a patients prescribed for AF treatment, resulting in fewer occurrences of stroke throughout the

Montoya- GR, AC, National Institutes Device for Left Atrial Appendage AF patient population. The device will be the first LAA occlusion method employing suction

NCSU Weiss, Mitzi M. $438,834 $0 X HE, OE of Health Occlusion and the first to use SMA tendons. Use of SMA tendons will pave the way for other devices 10/1/2009 9/30/2011 93.701 2009-2265 5/1/2009



The Lila Lab will be responsible for preparing exogenously 14C labeled bioactive fractions and

subfractions (primarily isoflavone-rich fractions from kudzu and from red clover) for the

metabolic tracking studies. The postdoctoral research associate will work with a Senior

Purdue University Research Associate to rigorously characterize the structural chemistry of labeled fractions that

(National Institutes Botanical Center For Age-Related will be administered in vivo. As appropriate, analysis of metabolites in the animal serum and 93.701,

NCSU Lila, Mary Ann $50,000 $0 X ET, HE, OE of Health) Diseases tissue will be subsequently examined. 7/1/2009 6/30/2011 93 2009-2274 5/1/2009



NCSU will employ St. thermophilus as a cloning and expression host for the Alanyl-Glutamine

(Ala-Glu) rich peptides in an effort to orally deliver maximum amounts of the these peptides,

in vivo. NCSU will identify the optimum bile sensitive strain of St. thermophilus for cloning and

expression of these peptides. NCSU will make the genetic constructs, both plasmid and

chromosomal based. The genes for the peptides will be synthesized using optimal codon usage

for St. thermophilus. Expression of the peptides will be examined and steps taken to maximize

expression using strong constitutive and inducible promoters. Lastly, strains selected as

cloning and expression hosts will be examined for bile induced release of the peptides from

intracellular locations. These constructs will be sent to University of Virginia for evaluation of

University of Tailored Probiotic Delivery of efficacy in their models. NCSU will make genetic modifications, as needed throughout the

Klaenhammer, Virginia (National Glutamine-rich Peptides for study, in order to optimize expression and delivery of the peptides to the gastrointestinal

NCSU Todd R. $226,097 $0 X ET, HE, OE Institutes of Health) Intestinal Repair. tract. 9/30/2009 9/29/2011 93.701 2009-2276 5/1/2009









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The team of urologists at Wake Forest University have made great strides in using natural

decellualar matrices (ECM's) for the repair of tubular urethra, bladder or ureter tissues. While

this approach has yielded positive results, it cannot work equally well with every patient,

because the natural biological matrix is non-uniform and does not provide a consistent and

uniform size, shape and structural integrity to the scaffold and its tissue construct. Martin King

and his team at NCSU have experience using collagen and synthetic resorbable polymers to

prepare uniform and consistent porous elastomeric fiber based scaffolds. They use a number

of fiber spinning and textile fabrication techniques, such as melt spinning, electrospinning,

weaving, knitting and braiding. In this project they plan to combine tubular webs of

electrospun nanofibers with knitted and woven pile structures made from synthetic

resorbable polymers, collagen and/or elastin. However, first it will be necessary to melt or wet

Application of Advanced Fiber spin continuous filaments of nanofiber yarns using a biconstituent fiber spinning process.

GR, AC, National Institutes Technologies for Emgineering These yarns can then be used to knit and weave appropriate pile fabrics with a large enough

NCSU King, Martin W. $960,555 $0 X HE, OE of Health Hollow Renal Tissues surface area to regenerate tubular urethral structures. The WFIRM team will then implant the 9/30/2009 9/29/2011 93.701 2009-2285 5/5/2009



The role of Martin King and his team at NCSU is to fabricate, sterilize and provide tissue

engineering scaffolds that will serve as an extracellular matrix (ECM) for growing pancreatic

islets in experimental quantities. The NCSU team has experience in preparing highly porous

and bioresorbable fiber based scaffolds made from different synthetic resorbable polymers as

well as collagen using a number of fiber spinning and textile fabrication techniques, such as

melt spinning, electrospinning, weaving, knitting and braiding. In this project they plan to

combine electrospun nanofiber webs, knitted or woven pile stuctures with a bioactive surface

coating of collagen and/or laminin. However, first it will be necessary to melt or wet spin

continuous filaments of nanofiber yarns using a biconstituent fiber spinning process. These

yarns can then be used to knit and weave appropriate pile fabrics with a large enough surface

UNC - UNC Chapel area, suitable for pancreatic islet culture. The UNC-CH team will then implant the derived

GR, AC, Hill (National Progenitor Cell Differentiation and tissue constructs in an animal model so as to be able to evaluate their cell viability and

NCSU King, Martin W. $170,105 $0 X HE, OE Institutes of Health) the Generation of Neo-islets functionality in producing insulin. 9/30/2009 9/29/2011 93.701 2009-2287 5/5/2009

Research and anecdotal evidence provide increasing evidence that crimes against Hispanics

are less likely to be reported to law enforcement; if reported, they are less likely to be cleared

by arrest; and if cleared by arrest, they are less likely to be prosecuted. The high rate of

attrition of Hispanic victims in the criminal justice system results permits suspects to continue

to offend, often targeting similar vulnerable victims. Victim attrition undermines the

confidence of Hispanics in the criminal justice system, leaving them highly vulnerable to

further victimization. In this project, N.C. State University will work with three of North

Carolina's District Attorneys representing prosecutorial districts that have had rapid increases

in their Hispanic population and increases in violent crime. NCSU will assist the DA's in hiring

Victim/Crime Prevention Coordinators to collaborate with local law enforcement agencies and

assist Hispanic victims. Hispanic robbery victims will be provided with wrap-around assistance

from the initial report of the crime to responding law enforcement officers and will supervise

Weisel, Enhancing Arrest and Prosecution progress of the case through judicial disposition, bridging gaps between crime investigation

NCSU Deborah L. $592,967 $0 X ET, HE, OE US Dept. of Justice of Suspects Victimizing Hispanics and adjudication and reducing the attrition of victims. We anticipate that the services 8/1/2009 7/31/2011 16.808 2009-2289 5/5/2009









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Disorders of the nervous system have significant negative affects on society. In order to

address this problem, there is an urgent need to develop new techniques to monitor neuronal

activity that will enable improved understanding of the nervous system, and more specifically

brain function. These include ultrasensitive neurotransmitter detection techniques based on

previously developed nanofabrication technologies. The expected result of the innovative

nanofabrication work will be the creation of next-generation sensing devices and

methodologies. In the proposed work, these devices and methodologies will be applied to

monitor exocytotic release from individual neurons and model neurons to improve

understanding of the mechanisms of exocytosis. The expected result of this effort will be new

analytical tools that will enable ultra-sensitive detection of neurologically related molecules of

interest in extremely small volumes of ionic solution. The measurement of these molecules

will enable the acquisition of neuro-physiological data that was not practically available

previously. The analysis of this now available data will lead to new treatment methods for

McCarty, National Institutes Implementing Nanogap Sensors in neurological and neurodegenerative disorders. While these techniques are applicable to a

NCSU Gregory S. $56,534 $0 X HE, OE of Health Neuroscience Research variety of problems in the sciences, initial applications will be focused on neuronal function 5/1/2007 6/30/2010 93.701 2007-0509 5/5/2009

We propose to purchase a new, state of the art X-ray generator, CCD detector and cryo

system to support on-going crystallographic studies at North Carolina State University (NCSU).

In addition we propose to expand our capabilities by adding a small angle X-ray scattering

(SAXS) detector on the second port of the generator. The generator will replace two obsolete

and difficult to maintain generators that are 18 and 19 years old. The generator would be

housed in the newly renovated crystallography facility. Protein crystallography and structural

biology are currently well established and growing at NCSU, requiring access to a more

reliable high intensity source. Crystallographic studies are contributing to a wide variety of

biomedically important topics at NCSU including the study of ras mutations activated in many

cancers, characterizing mutations in transcription factors associated with diabetes, defining

the mechanism of activation of caspases and evasion of apoptosis in cancers, defining the

A High Flux X-Ray Generator For mechanism of RNA modifications required for ribosome assembly, and characterizing the

National Institutes Protein Crystallography and Small structure of a plant virus to be used for drug delivery. The X-ray generator will also support

NCSU Rose, Robert B. $1,232,168 $0 X ET, HE, OE of Health Angle Scattering new efforts in neutron crystallography through ties with Oak Ridge National Labs. This 12/1/2009 11/30/2010 93.701 2009-2293 5/5/2009



Six week summer educational training delivered by staff in Nash, Edgecombe, Wilson, Halifax,

and Northampton Counties to 120 youth. All youth will work 32 hours per week on job sites

through CES and required to attend educational training for 8 hours per week for a total of 40

Turning Point WDB, hours per week. Grant is from stimulus dollars for targeted youth, ages 14-24 years of age.

Sykes, Wanda GR, AC, Inc. (US Dept. of RISE Respect and Integrity through Three temp employees (3 month employment only) will be hired to work with youth to secure

NCSU D. $290,000 $0 X ET, HE, OE Labor) Skills and Education eligibility, secure job placement and assist in educational training component. 6/1/2009 8/14/2009 17.259 2009-2299 5/5/2009



Blankenship, GR, AC, National Institutes Avian National Resource for Renovation of House 231 Lake Wheeler Road and Dearstyne Unit to support Avian Biomedical

NCSU Sylvia M. $4,943,518 $0 X ET, HE, OE of Health Ovarian Cancer Research Ovarian Cancer Research 12/1/2009 11/30/2012 93.702 2009-2312 5/6/2009

This application addresses broad Challenge Area (13): Smart Biomaterials-Theranostics, and

specific Challenge Topic, 13-DK-104: Islet Encapsulation, namely, the Development of novel

islet encapsulation technologies/biomaterials for the optimization of a bioartificial pancreas.

Microencapsulated islets offer the potential to fundamentally cure diabetes and prevent its

complications thereby improving the quality of life of millions of Americans and reduce the

health care cost in the United States. The science and technology of bioartificial pancreas for

the cure of diabetes is sufficiently well developed from a biomedical point of view. Islet

transplants with the Edmonton immunosuppressive regimen and microencapsulated islets

from human and animal donors transplanted without immunosuppressive drugs have been

shown to reverse diabetes in small animals, non-human primates, and humans. The appeal of

the encapsulation technology is its potential to expand the islet donor source such as the use

Massively Parallel Approaches for of pig islets. While, encapsulated pig islets have been successfully used to reverse diabetes in

Ramasubraman GR, AC, National Institutes the Large Volume Production of non-human primates, a major obstacle to realizing the full promise of the technology is the

NCSU ian, Melur K. $949,070 $0 X ET, HE, OE of Health Microencapsulated Islets lack of large scale devices to encapsulate sufficient quantities of viable islets for clinical 10/1/2009 9/30/2011 93.701 2009-2332 5/8/2009









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American Recovery and Reinvestment Act 2009

Preliminary Notice, Proposals and Awards





North Carolina State University (NCSU) and Oak Ridge National Laboratory (ORNL) will

collaborate to develop a holistic (fundamental and accurate) approach for generating thermal

neutron scattering cross section libraries for a collection of important neutron moderators

and reflectors. The primary components of this approach are the physical accuracy and

completeness of the generated data libraries. Consequently, for the first time, thermal

neutron scattering cross section data libraries will be generated that are based on accurate

theoretical models, that are carefully benchmarked against experimental and computational

data, and that contain complete covariance information that can be used in propagating the

data uncertainties through the various components of the nuclear design and execution

process. To achieve the above objectives, NCSU and ORNL will perform computational and

Accurate Development of Thermal experimental investigations of a carefully selected subset of materials that play a key role in all

Neutron Scattering Cross Section stages of the nuclear fuel cycle. The chosen materials are beryllium (Be), reactor-grade

Hawari, Ayman Libraries for Advanced Fuel Cycle graphite, light water (H2O), and silicon dioxide (SiO2). All these materials are important

NCSU I. $514,741 $0 X ET US Dept. of Energy Applications neutron moderators and reflectors. Graphite and H2O are also the main moderators in key 10/1/2009 9/30/2012 81.049 2009-2336 5/8/2009



Pregnant women have been identified as a high risk group for foodborne illness as well as

poor nutrition. Food choices during pregnancy can impact the health of both mother and

child, with risky choices resulting in long-term health consequences. Much information on

food risks such Listeria monocytogenes, methyl mercury and poor diet exist in the public

health literature but connecting with moms-to-be and engaging the audience in a meaningful

discussion around food risks has been problematic. To aid in better food choices and impact

risk-reduction behavior, subject matter experts in food safety and nutrition will create,

participate and populate social media networks. Through focus groups information tone, style

and messages will be developed and tested. Using the results of the focus groups, popular

information sources such as mommy blogs, Facebook, Twitter, Wikipedia and YouTube will be

Investigation, Development and used to connect experts and extension personnel directly with the target audience. An

Evaluation of Social Media evaluation of the effectiveness of the social media networks as an information channel will be

Chapman, GR, AC, National Institutes Networks Supporting Food Choices conducted using self-reported diary techniques, in-depth interviews and behavior

NCSU Benjamin $595,334 $0 X HE, OE of Health of Moms-To-Be assessments. 10/1/2009 9/30/2011 93.701 2009-2350 5/11/2009

The purpose of this application is to examine how bacteriophage resistance confers

attenuation, while preserving immunogenicity of a Listeria monocytogenes strain that is oral-

virulent for mice. Mutants of listerial strain F6214-1 that are resistant to phage P35h4 are

attenuated when inoculated orally into female A/J mice and show impaired replication in

cultured mouse enterocytes. One of these mutants, containing a Tn917 insertion in the glcV

gene, has been extensively characterized. Phage binding studies indicate that the mutant has a

cell surface alteration that precludes phage attachment. All phenotypes associated with the

mutation are complemented in trans by a parental copy of the glcV gene. The glcV gene is

Southeast Regional predicted to encode a group 2 glycosyl transferase. Interestingly, the glcV lesion, while

Center of Excellence preventing phage attachment, does not affect the mutant?s ability to bind to cultured mouse

for Emerging enterocyte monolayers. Rather, the mutation appears to alter a subsequent step in

Infections and intracellular replication measured as a reduction in plaque forming efficiency and plaque size

Biodefense Immunogenicity of an Attenuated in enterocytes. In vivo, the mutant is, in contrast to the highly invasive parent strain,

Orndorff, Paul (SERCEB) (National Listeria Monocytogenes undetectable in the liver and spleen 48 h post oral inoculation. The mutant is important, in

NCSU E. $605,161 $0 X HE Institutes of Health) Bacteriophage Resistant Mutant part, because of its outstanding potential as a live oral vaccine platform. Impediments to 6/15/2009 6/14/2011 93.856 2009-2351 5/11/2009



The proposed research aims at laying the fundaments for developing a sequencing device that

Sequencing DNA by Transverse can be deployed at point-of-care locations. In this capacity it will help guide therapies in which

National Institutes Electrical Measurements in the genetic makeup of a patient is important to the suitability of treatments, or where the

NCSU Riehn, Robert $48,623 $0 X HE of Health Nanochannels genetic identity of pathogens must be known. 9/1/2007 7/31/2010 93.701 2007-0869 5/12/2009









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American Recovery and Reinvestment Act 2009

Preliminary Notice, Proposals and Awards





This application addresses broad Challenge Area (06):Enabling Technologies and specific

Challenge Topic,06-GM-106: Subcellular imaging of metal ions. This project addresses the need

to identify the types of metal ions present in a nanometer-sized (subcellular) region, and

identification of the valence state of those ions. Both aspects of the measurement are crucial

for evaluating the local physiological state of the cell. The ion concentration is crucial for

signaling and metal assisted transport in the cell. The valence state is crucial for understanding

the activity of the particular ions. Ions at different valence states will have very disparate

reaction properties, so will participate differently in cell processes. Imbalance in metal ion

concentrations can result in cell death, while knowledge of how cells regulate ion

concentration and valence can elucidate function and suggest approaches for treatment of

disease cause by or causing ion imbalance. The project will focus on the development of a

Nanoscale Measurement of Metal novel probe rather than use of an existing probe. The design builds upon several past projects,

National Institutes Ions and Valence with Wide-Band and consists of a capillary tube drawn to a point, plugged with an ion nonselective membrane,

NCSU Hallen, Hans D. $485,355 $0 X ET of Health Optical Sensors filled with fluid and one or more types of indicator molecules, and sensed via an optical fiber 9/30/2009 9/29/2011 93.701 2009-2359 5/13/2009





The purpose of this administrative supplement to the NC State Initiative for Maximizing

Student Diversity (IMSD) Program is to increase and extend the science and training

opportunities to IMSD students. Funds from the supplement will allow the program to engage

biomedical and behavioral science researchers, both internal and external to NC State

University, to participate in various professional development and research components of

the program. This will contribute to broadening of students? exposure to the research being

conducted and the professional development and training opportunities available to them in

the areas of biomedical and behavioral sciences. Additionally, this supplement will allow for

recruitment and support of individuals with skills that will help to enhance the overall

experience for the IMSD students. Although the aforementioned activities are being

implemented successfully with funds from the parent grant, funds from the administrative

MacKay, Trudy National Institutes Initiative for Maximizing Student supplement will accelerate the tempo and reach of the program, and improve the ways in

NCSU F. $114,524 $0 X ET, HE, OE of Health Diversity which the current activities are being implemented. 2/1/2008 1/31/2012 93.701 2007-1385 5/13/2009

The purpose of this application is to explore the feasibility of using a bacteriophage resistant

mutant of Listeria monocytogenes as an attenuated, oral vaccine delivery platform. Mutants

of listerial strain F6214-1 that are resistant to phage P35h4 are attenuated when inoculated

orally into female A/J mice and show impaired replication in cultured mouse enterocytes. One

of these mutants, containing a Tn917 insertion in the glcV gene, has been extensively

characterized. Phage binding studies indicate that the mutant has a cell surface alteration that

precludes phage attachment. All phenotypes associated with the mutation are complemented

Southeast Regional in trans by a parental copy of the glcV gene. The glcV gene is predicted to encode a group 2

Center of Excellence glycosyl transferase. The loss of this product results in a defective phage receptor and alters

for Emerging the normal host-pathogen interaction required for virulence. Interestingly, the glcV lesion,

Infections and while preventing phage attachment, does not affect the mutant?s ability to bind to cultured

Biodefense mouse enterocyte monolayers. Rather, the mutation appears to alter a subsequent step in

Orndorff, Paul (SERCEB) (National intracellular replication measured as a reduction in plaque forming efficiency and plaque size.

NCSU E. $616,954 $0 X HE Institutes of Health) Live Oral Listeria Vaccine Vector In vivo, the mutant is, in contrast to the highly invasive parent strain, undetectable in the liver 6/15/2009 6/14/2011 93.856 2009-2361 5/13/2009









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American Recovery and Reinvestment Act 2009

Preliminary Notice, Proposals and Awards





This application addresses broad Challenge Area (05) Comparative Effectiveness Research and

specific Challenge Topic 05-HL-105: Optimizing of anti-platelet treatment after

revascularization procedures. Dual thienopyridine-aspirin anti-platelet therapy, in particular

clopidogrel+aspirin, has been shown to lower the risk of thrombotic complications in patients

with bare-metal and drug-eluting stents but raise the risk of serious bleeding events.

Accordingly, despite numerous studies yielding valuable insights toward optimizing anti-

platelet regimen in these patients, considerable uncertainty remains on the best strategies to

recommend for either type of device. In this project, a new approach will be taken to

identifying optimal anti-platelet therapy regimens that takes into account the fact that

management of patients following stent implantation is really a dynamic process that involves

a series of therapeutic decisions made over time; these include the initial decision on anti-

platelet maintenance regimen and duration, subsequent decisions on whether or not and how

National Institutes Optimal Anti-Platelet Regimes and to modify the regimen if the patient experiences an intercurrent event, and whether or not

NCSU Davidian, Marie $725,307 $0 X HE of Health Clinical Trials Via Learning Methods and how to extend therapy when the intended duration is reached. At each of these ?decision 9/30/2009 9/29/2011 93.701 2009-2362 5/13/2009

Screening of saliva and other oral fluids offers potentially faster, cheaper and safer diagnostic

method than conventional blood sampling. Human saliva contains a large number of proteins

involved in various biological functions including digestion and modulation of microbial levels

and metabolism. Blood pool proteins are also present in saliva in the same relative

concentration. It is now established that the presence of specific bacteria and/or metabolites

could be used for diagnostics of early childhood caries, periodontal diseases, and oral cancer.

While the research in saliva proteomics continues to advance by combing state-of-the art

mass spectrometry and 2-D gel electrophoresis, there is an urgent need for developing new

technologies for rapid label-free screening of oral fluids. We propose to fill the gap in existing

technologies by developing a biosensing platform that is based on newly introduced metallic

New Jersey Institute screens with periodic openings. The screens are covered with graphene - a monolayer of

of Technology carbon crystal. Graphene has many benefits of graphite (biocompatibility, chemical inertness,

Smirnov, Alexej (National Institutes Monitoring Proteins by Graphene absence of IR signature in the 2-20 micron region). The unique electric properties of the

NCSU I. $200,000 $0 X HE of Health) Coated Infrared Platforms graphenated IR screens lead to concentrating the electric field in the centers of the screen 9/30/2009 9/29/2011 93.701 2009-2364 5/13/2009

This application addresses broad Challenge Area (07) Enhancing Clinical Trials and specific

Challenge Topic 07-DK-101: Enhancing clinical trials in diabetes, obesity, and metabolic,

endocrine, digestive, liver, renal and urological diseases. A key issue in solid organ

transplantation is how best to use immunosuppressive medications to prevent rejection of the

transplanted organ. Immunosuppressive strategies must strike a delicate balance between

suppressing the immune system well enough to prevent rejection of the organ and organ

dysfunction and maintaining sufficient immune system response to avoid serious infections,

adverse side effects, and malignancies. Guidelines for using immunosuppressive therapies vary

substantially across different transplant centers, which is a consequence of the unresolved

questions and lack of consensus on how best to use the classes of available

immunosuppressive agents and other therapies. There is thus a critical need for research on

the development of evidence-based immunosuppressive strategies that optimize the long-

Modeling of Immunosuppression term management of transplant recipients. Focusing on renal transplantation, this project will

National Institutes and Clinical Trials in Renal take a new approach to the study of immunosuppression based on quantitative modeling of

NCSU Davidian, Marie $990,425 $0 X HE of Health Transplantation the processes of immunosuppression, which will be facilitated through the efforts of an 9/30/2009 9/29/2011 93.701 2009-2365 5/13/2009









ab25087a-b4cd-4a92-bc82-1fd227824da0.xls 8/22/2009, 2:35 AM

American Recovery and Reinvestment Act 2009

Preliminary Notice, Proposals and Awards





This is a request for an administrative supplement to enable incorporating a proteomics

component in specific aim 2 of grant R01-GM059469 (Molecular genetics of olfaction in

Drosophila). This specific aim focuses on assessment of naturally occurring variation and

environment-dependent plasticity in expression of chemoreceptors in Drosophila through

transcriptional profiling using expression microarrays. The requested supplement will remain

within the scope of this specific aim, but enhance its impact by enabling a correlation between

the transcriptome and the proteome thus providing a more complete picture of

environmental plasticity of chemoreceptor expression, specifically expression of odorant

binding proteins. In preliminary experiments we have established the ability to identify soluble

proteins from the Drosophila antenna using high resolution mass spectrometry. During the

first year of support we will measure expression of odorant binding proteins between virgin

and mated males and females, young versus old flies, and males and females reared in groups

or in isolation or exposed to same sex or opposite sex odor in a standard laboratory Canton S

Anholt, Robert GR, AC, National Institutes Molecular Genetics of Olfaction in (B) strain, and compare protein expression to previously measured transcriptional modulation.

NCSU R. $323,457 $0 X HE, OE of Health Drosophila Based on the results with our Canton S (B) flies, we will target a select number of odorant 7/1/2005 3/31/2012 93.701 2006-0475 5/13/2009



One of the primary goals of the iniatives in in Applications of Nuclear Science and Technology

is the measurement of relevant nuclear data required for advanced reactor fuel cycles. The

neutron capture reaction is very important for the design of the proposed new advanced fuel

Measurement and Analysis of cycle reactors. We propose to measure the neutron capture reaction using the Detector for

Neutron Capture Data for Advanced Neutron Capture Experiments at Los Alamos National Laboratory. In addition to

Mitchell, Gary GR, HE, Advanced Reactor Fuel Cycles and measuring specific key elements, there will be focus on improving the understanding of the

NCSU E. $405,000 $0 X OE US Dept. of Energy Other Applications parameters used in the modeling of the capture reaction. 7/1/2009 6/30/2011 81.049 2009-2367 5/13/2009

The gray, short-tailed opossum, Monodelphis domestica is the predominant laboratory-bred

research marsupial in the world and is used in investigations that span a broad range of topics

relevant to human development, physiology, and disease susceptibility. The recently

completed opossum genome sequence furnishes a critical resource for examining the

evolutionary histories of vertebrate genomes in general and is fostering the development of

new research tools for M. domestica that are expanding its versatility as an experimental

system for a broad range of research applications in basic biology and biomedically oriented

research. The fine-scale accuracy of the opossum sequence is very high and has enabled in-

depth analyses of gene structure, gene content, non-coding element content, and other

Texas A & M characteristics that exist in the range of kilobases (Kb) to a few megabases (Mb). However, as

Research is generally true for newly assembled genome sequences, the large-scale structure contains

Foundation many uncertainties that render studies of regional structure and long-distance functional

Breen, (National Institutes Gene Expression Arrays for the interactions difficult or impossible. In attempting to integrate the opossum genetic linkage

NCSU Matthew $177,721 $0 X ET of Health) Laboratory Opossum map and genome assembly, we detected several examples wherein the linkage map and 7/1/2009 6/30/2011 93.701 2009-2371 5/13/2009

Our overall goal is to identify novel mechanisms by which viruses subvert the host innate

antiviral response to cause disease. Here, we will investigate viral modulation of

immunoreceptor tyrosine-based activation motif (ITAM) pathways during the innate antiviral

response, an interaction not previously investigated for any virus. Viral infections stimulate an

array of innate protective responses. For example, viruses can induce expression and

secretion of interferon-beta (IFN-beta), to induce expression of antiviral genes in neighboring

cells. Not surprisingly, viruses have evolved diverse mechanisms to subvert this IFN response.

ITAM-associated cell receptors can modulate IFN and other cytokine signaling, and yet viral

Southeast Regional subversion of ITAMs has not previously been studied. While several enveloped viruses encode

Center of Excellence viral ITAMs which function as oncogenes, no other viral ITAM functions have been identified.

for Emerging We hypothesize that viral ITAMs can subvert the innate antiviral response. The non-enveloped

Infections and Reoviruses provide an excellent model to study host innate responses. We previously

Biodefense Viral Subversion of identified three viral genes associated with reovirus strain-specific differences in induction of

(SERCEB) (National Immunoreceptor Tyr-Based and sensitivity to IFN: the M1, S2 and L2 genes. More recently, we demonstrated that M1

NCSU Sherry, Barbara $588,748 $0 X ET, HE, OE Institutes of Health) Activation Motif (ITAM) Signaling encodes a repressor of IFN signaling, but additional M1 roles and roles for S2 and L2 remain 6/1/2009 5/31/2011 93.856 2009-2375 5/13/2009

We will apply new concepts developed from recent in vitro modeling of normal human

National Institutes Differentiation of Alveolar alveolar eipthelial cell differentiation and in vivo modeling of pulmonary fibrosis in rats to

NCSU Sannes, Philip L. $0 $74,459 X HE of Health Epithelium and Pulmonary Fibrosis study novel ideas 5/11/2009 4/30/2010 93.701 2008-2185 5/13/2009









ab25087a-b4cd-4a92-bc82-1fd227824da0.xls 8/22/2009, 2:35 AM