American Recovery and Reinvestment Act 2009

Document Sample
American Recovery and Reinvestment Act 2009 Powered By Docstoc
					                                                                                                                                           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

                                   Amount           Amount         Prelim.                         UNCT
Campus          PI                 Requested        Awarded        Notice        Prop.   Award     Code           Sponsor         Title                              Summary                                                                                           Begin Date     End Date      CFDA#        SPS #
                                                                                                                                                                     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                                                     2009-
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 1874
                                                                                                                                                                     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                                                  2009-
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 1909

                                                                                                            Development Board
                Sykes, Wanda                                                                     GR, AC,    (NC) (US Dept. of                                                                                                                                                                                   2009-
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 1911
                                                                                                                                                                       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                                                        2009-
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 1930

d0c0ac99-0c11-46c0-b8fb-7bfdd054fcff.xls                                                                                                                                                                                                                                                                 9/12/2011, 9:48 AM
                                                                                                         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 the optimal
                                                                         Mayo Foundation        Development of Medication          treatment guideline. We will evaluate whether medication prioritization changes for older
                                                              GR, AC,    (National Institutes   Algorithms for Complex Elderly     patients and how such changes depend on the degree of adherence and presence of                                                        2009-
NCSU            Denton, Brian          $233,892      $0   X   HE, OE     of Health)             Patients                           comorbidities.                                                                                          10/1/2009   9/30/2011   93.701 1988
                                                                                                                                   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                                           2009-
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 1998
                                                                                                                                   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                                                 2009-
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 2004
                                                                                                                                   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                                         2009-
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

d0c0ac99-0c11-46c0-b8fb-7bfdd054fcff.xls                                                                                                                                                                                                                           9/12/2011, 9:48 AM
                                                                                                          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                                          2009-
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 2020
                                                                                                                                  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 dereplication process has
                                                                         Rutgers University Novel Antimalarial and                been completed and the novelty of the structure is determined, we will utilize a
                                                              GR, AC,    (National Institutes Antiinfective Pharmacological Leads comprehensive, state of the art NMR suite (400-950 MHz) available in the Core Laboratory of                                              2009-
NCSU            Lila, Mary Ann         $196,001      $0   X   ET, HE, OE of Health)           from Plants                         the NCRC. As resident faculty on the campus, our laboratory team has unrestricted access to               10/1/2009   9/30/2011   93.701 2029
                                                                                                                                  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 between                                            1991-
NCSU            Sannes, Philip L.      $225,720      $0   X   HE, OE     of Health            Interactions in the Lung            alveolar epithelial cells and their ECM microenvironment. This is significantly modulated by               4/1/1992   3/31/2014   93.838 1541

d0c0ac99-0c11-46c0-b8fb-7bfdd054fcff.xls                                                                                                                                                                                                                            9/12/2011, 9:48 AM
                                                                                                        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 variation in response to
                                                                         Duke University                                        therapeutic agents. In this supplemental application we propose to add informatics and
                                                                         Medical Center                                         pathway analysis capabilities that can accelerate significantly the effort of the network creating
                Zeng, Zhao-                                   GR, AC,    (National Institutes Metabolomics Network For Drug     and retaining jobs in-line with the Recovery Act Funds for Administrative Supplements (NOT-                                                  2009-
NCSU            Bang                       $27,492   $0   X   ET, HE, OE of Health)           Response Phenotype                OD-09-056). Additionally we propose to develop standards that can accelerate developments             12/14/2008    6/30/2011         93.701 1978
                                                                                                                                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                                                  2004-
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; 93.702 0472

                                                                                                                                  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                                                2009-
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 2062
                                                                                                                                  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                                          2009-
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 2077

d0c0ac99-0c11-46c0-b8fb-7bfdd054fcff.xls                                                                                                                                                                                                                              9/12/2011, 9:48 AM
                                                                                                       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 in human
                                                                                               Ethics of Nanomedical           health with constructed nanoscale materials raises new questions about risks, benefits, and
                                                                                               Technologies: Perceptual        safety regulations. Most new nanotechnology advancements have resulted from teams of
                Jones, Melissa                                           National Institutes Differences Across Domains and    researchers from distinct fields of study who have traditionally worked within separate                                          2009-
NCSU            G.                     $655,281      $0   X   HE, OE     of Health             Degrees of Expertise            communities of practice. We know little about how researchers within these different              10/1/2009   9/30/2011   93.701 2087
                                                                                                                               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                                          2003-
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 1335
                                                                                                                               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 methylation patterns
                                                                         Northwestern                                          similar to those seen in high pesticide exposed individuals, 3) Investigate whether pesticides
                Wallace,                                                 University (National DNA Methylation Alterations in   can directly affect the methylation of specific genes. This research is important and timely.                                    2009-
NCSU            Andrew Daniel              $90,802   $0   X   HE, OE     Institutes of Health) Response to Pesticide Exposures With our increasing reliance upon pesticides, their untoward effects will only have increased     10/1/2009   9/30/2010   93.701 2092

                                                                                                                                 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                                    2009-
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 2095

d0c0ac99-0c11-46c0-b8fb-7bfdd054fcff.xls                                                                                                                                                                                                                 9/12/2011, 9:48 AM
                                                                                                      American Recovery and Reinvestment Act 2009
                                                                                                        Preliminary Notice, Proposals and Awards

                                                                       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                                             2009-
NCSU            M.                         $73,010   $0   X   HE, OE   Institutes of Health) Transgenic Pigs                humans.                                                                                               9/30/2009    9/29/2010   93.701 2096
                                                                                                                            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                                             2009-
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 2097

                                                                                                                               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 acoustic
                                                                       University of         Pro-Bubbles For Ultrasound        parameters required for radiation force assisted localization and marginalization of pro-
                                                                       Arizona (National     Imaging and Treatment of Prostate bubbles; and 3) image activated pro-bubbles in vivo to determine scattering capabilities and                                       2009-
NCSU            Dayton, Paul A.        $399,026      $0   X   HE, OE   Institutes of Health) Cancer                            sensitivity to imaging utilizing optimized ligands, pro-bubbles, and ultrasound.                   9/30/2009    9/29/2011   93.701 2101

                                                                                                                                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                                       2009-
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 2062

                                                                                                                                 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                                         2009-
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 2132

d0c0ac99-0c11-46c0-b8fb-7bfdd054fcff.xls                                                                                                                                                                                                                   9/12/2011, 9:48 AM
                                                                                                     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)                                         2009-
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 2135
                                                                                                                              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                                                      2002-
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 0368
                                                                                                                              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.                                         2009-
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 2137

d0c0ac99-0c11-46c0-b8fb-7bfdd054fcff.xls                                                                                                                                                                                                                     9/12/2011, 9:48 AM
                                                                                                     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-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.                                            2009-
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 2138
                                                                                                                             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                                                2009-
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 2139

                                                                                                                                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                                          2009-
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 2140
                                                                                                                                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                                             2008-
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 2455

d0c0ac99-0c11-46c0-b8fb-7bfdd054fcff.xls                                                                                                                                                                                                                      9/12/2011, 9:48 AM
                                                                                                    American Recovery and Reinvestment Act 2009
                                                                                                      Preliminary Notice, Proposals and Awards

                                                                                                                                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                                             2009-
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 2147
                                                                                                                                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                                             2009-
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 2149
                                                                                                                                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                                       2009-
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 2152

d0c0ac99-0c11-46c0-b8fb-7bfdd054fcff.xls                                                                                                                                                                                                                     9/12/2011, 9:48 AM
                                                                                                     American Recovery and Reinvestment Act 2009
                                                                                                       Preliminary Notice, Proposals and Awards

                                                                                                                               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                                           2009-
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 2159
                                                                                                                               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, maintain, or increase trust
                                                                                            Environmental Public Health,       capacity between research and public communities demands a different set of exercises and
                Berube, David                                         National Institutes   Organizational Trust, and Public   activities than one would undertake during a team-building workshop at a corporate retreat.                                          2009-
NCSU            M.                     $745,718   $0   X   HE, OE     of Health             Communities                        As such we offer a project with a series of building blocks. This process will produce new data       1/1/2010   12/31/2011   93.701 2160

                                                                                                                               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                                                   2008-
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 1247
                                                                                                                               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                                                2009-
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 2161

d0c0ac99-0c11-46c0-b8fb-7bfdd054fcff.xls                                                                                                                                                                                                                     9/12/2011, 9:48 AM
                                                                                                     American Recovery and Reinvestment Act 2009
                                                                                                       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 explore the mechanisms
                                                                                            The Challenge of Determining         through which CNTs activate specific cell signaling events linked to the progression of fibrosis
                Bonner, James                              GR, AC,    National Institutes   Whether Carbon Nanotubes             and/or cancer. The specific hypothesis to be tested in this proposal is that CNTs activate                                         2009-
NCSU            C                      $962,797   $0   X   ET, HE, OE of Health             Represent the Next Asbestos          growth factor and chemokine signaling pathways that act coordinately with the p53                  10/1/2009    9/30/2011   93.701 2162

                                                                                                                               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                                           2009-
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 2163
                                                                                                                               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                                         2009-
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 2165
                                                                                                                               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                                              2009-
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 2168

d0c0ac99-0c11-46c0-b8fb-7bfdd054fcff.xls                                                                                                                                                                                                                     9/12/2011, 9:48 AM
                                                                                                        American Recovery and Reinvestment Act 2009
                                                                                                          Preliminary Notice, Proposals and Awards

                                                                                                                                   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 in
                                                              GR, AC,    National Institutes   Isolation of Novel Targets to       which many microbial infections are multi-drug resistant and extremely difficult/impossible to                                      2009-
NCSU            Cavanagh, John         $997,778      $0   X   ET, HE, OE of Health             Remediate Vibrio Infections         treat. We have developed a lead compound that will inhibit and disperse biofilms across              9/30/2009   9/29/2011   93.701 2178
                                                                                                                                   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                                            2003-
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 1966

                                                                         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                                         2009-
NCSU            David                      $66,298   $0   X   HE, OE     Institutes of Health) Consortium                           Genetics Reource Consortium.                                                                        10/1/2008   8/31/2012   93.701 0725
                                                                                                                                    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                                                  1987-
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 1036

d0c0ac99-0c11-46c0-b8fb-7bfdd054fcff.xls                                                                                                                                                                                                                        9/12/2011, 9:48 AM
                                                                                                     American Recovery and Reinvestment Act 2009
                                                                                                       Preliminary Notice, Proposals and Awards

                                                                                                                                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
                                                                                                                                with the endosomal membrane. At normal pH, the two different lipids will be uniformly
                                                                      Polytechnic Institute Design of Multifunctional Doubly-   distributed across the liposome surface with the PEG tails hiding the fusion antibodies because
                                                           GR, AC,    of NYU (National      Fusogenic Liposomes For             DSPC is negatively charged at these conditions. At low pH, which is characteristic of the tumor                                   2009-
NCSU            Hall, Carol K.         $350,000   $0   X   ET, HE, OE Institutes of Health) Theranostic Applications            vasculature, the liposome membrane will phase separate into two domains because DSPC               10/1/2009   9/30/2011   93.395 2182
                                                                                                                                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                                               2009-
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 2186
                                                                                                                                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 Drosophila
                Anholt, Robert                             GR, AC,    National Institutes   Oxidative Stress and Neurogenetic   lines with fully sequenced genomes with variation in these behavioral phenotypes under                                            2009-
NCSU            R.                     $720,232   $0   X   HE, OE     of Health             Networks in Drosophila              control conditions and after paraquat exposure. The combined information from these two            10/1/2009   9/30/2011   93.701 2191

d0c0ac99-0c11-46c0-b8fb-7bfdd054fcff.xls                                                                                                                                                                                                                   9/12/2011, 9:48 AM
                                                                                                     American Recovery and Reinvestment Act 2009
                                                                                                       Preliminary Notice, Proposals and Awards

                                                                                                                                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                                       2009-
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 2195
                                                                                                                                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                                            2009-
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 2218
                                                                                                                                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 software;                                    2009-
NCSU            Bang                   $553,032   $0   X   ET, HE, OE of Health             Complex Traits                      and maintaining the interaction with users. The new features include various procedures             9/30/2009    9/29/2011   93.701 2197

d0c0ac99-0c11-46c0-b8fb-7bfdd054fcff.xls                                                                                                                                                                                                                     9/12/2011, 9:48 AM
                                                                                                      American Recovery and Reinvestment Act 2009
                                                                                                        Preliminary Notice, Proposals and Awards

                                                                                                                                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                                               2009-
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 2201

                                                                                                                                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                                                2009-
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 2206
                                                                                                                                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 therapeutics.                                      2009-
NCSU            Yaroslava              $321,800   $0   X   ET, HE, OE of Health             Telomerase RNA                      Toward this goal, we propose to conduct structural, thermodynamic, and dynamics studies of             9/30/2009   9/29/2011   93.701 2208
                                                                                                                                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                                     2009-
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 2212

d0c0ac99-0c11-46c0-b8fb-7bfdd054fcff.xls                                                                                                                                                                                                                       9/12/2011, 9:48 AM
                                                                                                       American Recovery and Reinvestment Act 2009
                                                                                                         Preliminary Notice, Proposals and Awards

                                                                                                                                   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                                                2009-
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 2213

                                                                                                                                 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                                               2009-
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 2215
                                                                                                                                 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 the                                               2009-
NCSU            Agris, Paul F.         $957,291   $0   X   HE, OE     Infectious Diseases Gram Positive Pathogens                field of antibacterial drugs, and antibiotic resistance have traditionally looked toward either          10/1/2009    9/30/2011   93.701 2217
                                                                                                                                 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                                                    2009-
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 2221

d0c0ac99-0c11-46c0-b8fb-7bfdd054fcff.xls                                                                                                                                                                                                                           9/12/2011, 9:48 AM
                                                                                                     American Recovery and Reinvestment Act 2009
                                                                                                       Preliminary Notice, Proposals and Awards

                                                                                                                              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                                         2009-
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 2222
                                                                                                                              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                                              2009-
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 2224

                                                                                                                               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 tool
                                                                      National Institutes   Generation Tool For Diagnostic and for the development of new diagnostic methods. We propose research to design and build                                                2009-
NCSU            Dutta, Rudra           $548,167   $0   X   HE         of Health             Other Healthcare Data              such a system, and develop algorithms for the distributed learning ability.                            10/1/2009   9/30/2011   93.701 2231

d0c0ac99-0c11-46c0-b8fb-7bfdd054fcff.xls                                                                                                                                                                                                                      9/12/2011, 9:48 AM
                                                                                                         American Recovery and Reinvestment Act 2009
                                                                                                           Preliminary Notice, Proposals and Awards

                                                                                                                                      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                                           2009-
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 2232

                                                                                                                                      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 decreasing                                       2009-
NCSU            M                      $194,859      $0   X   HE         Institutes of Health) Oncology                               medical errors in clinical radiation oncology.                                                        10/1/2009   9/30/2011   93.701 2235
                                                                                                                                      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                                           2009-
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 2236
                                                                                                                                      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                                                  2009-
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 2237

d0c0ac99-0c11-46c0-b8fb-7bfdd054fcff.xls                                                                                                                                                                                                                            9/12/2011, 9:48 AM
                                                                                                         American Recovery and Reinvestment Act 2009
                                                                                                           Preliminary Notice, Proposals and Awards

                                                                         UNC - UNC Chapel
                Tonkonogy,                                               Hill (National        Center for Gastrointestinal Biology                                                                                                                                              2008-
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 1740
                                                                                                                                   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-                                                        2009-
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 2259
                                                                                                                                   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                                                   2009-
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 2265

                                                                                                                                     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                                              2009-
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 93.701; 93.702 2274

                                                                                                                                     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
                                                                         University of         Tailored Probiotic Delivery of        intracellular locations. These constructs will be sent to University of Virginia for evaluation of
                Klaenhammer,                                             Virginia (National    Glutamine-rich Peptides for           efficacy in their models. NCSU will make genetic modifications, as needed throughout the                                                   2009-
NCSU            Todd R.                $226,097      $0   X   ET, HE, OE Institutes of Health) Intestinal Repair.                    study, in order to optimize expression and delivery of the peptides to the gastrointestinal tract.   9/30/2009    9/29/2011         93.701 2276

d0c0ac99-0c11-46c0-b8fb-7bfdd054fcff.xls                                                                                                                                                                                                                                 9/12/2011, 9:48 AM
                                                                                                     American Recovery and Reinvestment Act 2009
                                                                                                       Preliminary Notice, Proposals and Awards

                                                                                                                                  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 spin
                                                                                            Application of Advanced Fiber         continuous filaments of nanofiber yarns using a biconstituent fiber spinning process. These
                                                           GR, AC,    National Institutes   Technologies for Emgineering          yarns can then be used to knit and weave appropriate pile fabrics with a large enough surface                                       2009-
NCSU            King, Martin W.        $960,555   $0   X   HE, OE     of Health             Hollow Renal Tissues                  area to regenerate tubular urethral structures. The WFIRM team will then implant the derived         9/30/2009   9/29/2011   93.701 2285

                                                                                                                                  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                                          2009-
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 2287
                                                                                                                                  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                                        2009-
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 provided      8/1/2009   7/31/2011   16.808 2289

d0c0ac99-0c11-46c0-b8fb-7bfdd054fcff.xls                                                                                                                                                                                                                       9/12/2011, 9:48 AM
                                                                                                        American Recovery and Reinvestment Act 2009
                                                                                                          Preliminary Notice, Proposals and Awards

                                                                                                                                   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 neurological
                McCarty,                                                 National Institutes   Implementing Nanogap Sensors in     and neurodegenerative disorders. While these techniques are applicable to a variety of                                               2007-
NCSU            Gregory S.                 $56,534   $0   X   HE, OE     of Health             Neuroscience Research               problems in the sciences, initial applications will be focused on neuronal function due to the        5/1/2007    6/30/2010   93.701 0509
                                                                                                                                   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                                       2009-
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 2293

                                                                                                                               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                                                2009-
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 2299

                Blankenship,                                  GR, AC,    National Institutes   Avian National Resource for         Renovation of House 231 Lake Wheeler Road and Dearstyne Unit to support Avian Biomedical                                             2009-
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 2312

d0c0ac99-0c11-46c0-b8fb-7bfdd054fcff.xls                                                                                                                                                                                                                         9/12/2011, 9:48 AM

Shared By:
Description: Hyaluronic Acid Project Research Proposal document sample