PUBLIC HEALTH RELEVANCE: The proposed research aims to discover and develop medium-sized molecules that selectively inhibit the interaction of protein-RNA interactions that are absolutely essential for HIV-1 viral replication. If successful, these molecules will be the next generation drugs with novel mode of action as anti-HIV therapy.              The proposed research aims to discover and develop medium-sized molecules that selectively inhibit the interaction of protein-RNA interactions that are absolutely essential for HIV-1 viral replication. If successful, these molecules will be the next generation drugs with novel mode of action as anti-HIV therapy. __SpecificAimsTextDelimiter__  A. Specific Aims  The long-term goal of this work is to discover and develop molecular entities that can inhibit the functional interaction between HIV-1 protein and RNA elements (Tat-TAR RNA and Rev-RRE RNA) as effective alternative therapy for HIV/AIDS (Figure 1). One forefront of HIV research is the development of novel strategies that do not rely on combination therapy--highly active anti-retroviral therapy (HAART)--because this therapy is expensive, is not well tolerated, and resistance has started to emerge. We propose to develop inhibitors of protein-RNA interactions that are absolutely essential for the HIV life cycle-excellent targets widely recognized by the community. TAR and RRE RNAs are well-conserved noncoding sequences in the viral genome with defined targetable tertiary structures. The challenge in targeting these RNA structures is that it is difficult to find small molecules with the required selectivity, affinity and pharmacological properties to make it to the clinic. Larger, nucleic acid based inhibition such as RNAi or antisense are effective in-vitro but has suffered from stability and, more importantly, poor delivery inside of target cells. Herein, we propose to use medium-sized branched peptides and borono-branched peptides as cell permeable ligands for RNA with the selectivity, affinity and stability required to inhibit Tat-TAR and Rev-RRE interactions. This proposal is innovative because discovering molecules that inhibit HIV protein-RNA interactions can lead to novel therapy as anti-HIV drugs and to novel molecules that can selectively target RNA that are distantly related to antisense and RNAi agents. The scientific impact will be significant because the same class of compounds can be used to target other RNA structures important in biological pathways involved in disease states.  Inhibit RNA transcription or  RNA function = inhibit viral replication  multivalent  branched peptide HIV-1 RNA block protein binding site Figure 1. Inhibition of HIV-1 viral replication by targeting conserved tertiary RNA structures with multivalent branched peptides.  In the specific aims enumerated below, we expand our library of branched peptides for screening against TAR and RRE RNAs and evaluate the activities of hit compounds using biophysical methods as well as in vitro assays for selective inhibition of TAR and RRE function. Aim 1. To synthesize diversified short branched peptide and borono-branched peptide libraries and screen them against HIV-1 TAR and RRE RNA. We have recently shown that short branched peptides are selective ligands for TAR RNA with good binding affinity because of their capacity to form multivalent interactions; thus a continuation of these efforts is warranted.  1a. To synthesize medium-sized branched peptide libraries of different length  1b. To develop the synthesis of boron-containing amino acid analogs and incorporate them  into branched peptide libraries  1c. To develop a more stringent on-bead assay and screen synthesized libraries Aim 2. To evaluate "branched peptide hits" against TAR and RRE RNA using biophysical methods and cell-based assays. Determining the affinity and selectivity of RNA-binding molecules is important to aid in refining RNA ligand properties.  2a. To perform biophysical characterization (Kd measurements, selectivity and binding site  determination) of hit branched peptides  2b. To synthesize analogs of the hit compounds and define structure-activity relationships to  validate the binding site on TAR and RRE RNA  2c. To determine specificity of inhibition for Tat/TAR and Rev/RRE function using a variety of  cell based assays  2d. To assess the ability of the compounds to inhibit replication of HIV-1 and to measure cell  cytotoxicity


Hyperpolarized C-13 MRI Techniques to Monitor Radiation Therapy Response in Prostate Cancer Patients

PROJECT NARRATIVE The goal of this project is to develop new techniques and apply an innovative MR molecular imaging approach to monitor HP pyruvate metabolism in prostate cancer patients pre- and post-radiation therapy for the first time. While this study focuses on prostate cancer radiation therapy, these methods are designed to be applicable to other prostate cancer HP MRI studies and in general to other cancer investigations.


膵癌の低酸素ストレス耐性を標的とした新規治療開発

難治性消化器癌は豊富な腫瘍内間質増生から腫瘍組織内酸素濃度が低く、この低酸素環境に順応して癌の転移・浸潤・薬剤耐性など悪性形質を獲得している。申請者らは同一患者検体から高酸素・低酸素環境で樹立した異なる3Dオルガノイドを６ペア樹立しており、本研究では他の癌種から樹立したオルガノイドと低酸素環境下に対する細胞ストレス応答性を比較・検証する。細胞ストレスマーカー、かつ膵癌の予後増悪因子であるGDF-15をその指標として用い、低酸素環境下と通常酸素下でのその発現レベルの変化、細胞の悪性度や上皮間葉転換マーカーの発現を評価する。さらに、GDF-15発現を抑制する化合物Xによる抗腫瘍効果を検証する。

Japan Society for the Promotion of Science

Grant-in-Aid for Scientific Research (C)


Combined Cytological, Genomic, and Functional Mapping of Nuclear Genome Organization

PUBLIC HEALTH RELEVANCE:   Our goal is first to develop a genome-wide mapping strategy that predicts contact frequencies and cytological distances of genomic regions relative to all major nuclear compartments. Combining these predictions with other genomic and functional mapping data, our second goal is to determine what DNA sequence and epigenetic features determine nuclear compartmentalization and what impact nuclear compartmentalization has on DNA function.

UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN


NATIONAL CANCER PREVENTION AND CONTROL PROGRAM


Atrial Fibrillation: Bridging genetic discovery and clinical associations

Atrial fibrillation is an increasingly common and morbid cardiac arrhythmia associated with substantial risks of disabling stroke, heart failure, and death,  as well as with significant healthcare costs. It is now recognized that a widespread heritable component underlies atrial fibrillation, and common genetic variants have been discovered that associate with the arrhythmia. We seek to examine the relations between genetic variants associated with atrial fibrillation and clinical manifestations of the arrhythmia in order to asses whether applying genetic and other discoveries to patient management can reduce morbidity from atrial fibrillation.


Mobile X-ray photoelectron emission microscope

No summary - Aucun sommaire

Natural Sciences and Engineering Research Council of Canada

Research Tools and Instruments - Category 3 (>$325,000)


Élaboration d'un projet éducatif d'analyse de données du Grand Collisionneur de Hadrons (LHC)


CORRELATES OR MARKERS OF IMMUNITY IN AIDS


Mathematical Sciences: Quadratic Forms and Related Topics

This project is concerned with research on Witt rings and               quadratic forms.  The principal investigator will focus on the                  computation of Witt kernels for algebraic and transcendental field              extensions.  He will also continue his work on the theory of                    semidefinite polynomials and sums of even powers in rational                    function fields over a real-closed field, with particular attention             to quantitative questions on the higher pythagoras numbers of such              fields.  In another direction, he will carry out further                        investigations on Ore extensions over division rings, in the hope               that this will shed some light on the structure of division rings               themselves.                                                                             The research supported involves the theory of quadratic                 forms. This, in its simplest form, is the study of polynomial forms             of degree two.  Equivalently, it is an analysis of the types of                 inner products that can define the metric geometry of an                        n-dimensional vector space.


Doctoral Dissertation Research: Uniting genre analysis and multidimensional analysis: A corpus based analysis of scientific research articles

Under the direction of Dr. Jeff Connor-Linton, Ms. Budsaba Kanoksilapatham will compile and analyze a corpus of 60 biochemistry research articles. These articles will be randomly selected from five core journals in biochemistry published in the United States. Previous studies of discourse structure and language use in scientific articles have emphasized the communicative functions of rhetorical moves (like 'Summarizing previous research,' and 'Identifying a research niche') and of a few lexical and grammatical features (like past tense and passive voice). Ms. Kanoksilapatham will address both levels of analysis to determine how they are connected. She will analyze rhetorical moves to determine the rhetorical organization conventionally used in each of the four sections of biochemistry research articles (Introduction, Methods, Results, and Discussion) and to assess the reliability of move identification. She will then analyze the use of dozens of lexical and grammatical features to identify the sets of features that are most typically used to construct each type of move.

The importance of this research is threefold. Empirically, the study will offer the most representative review of the rhetorical structure of research articles to date. Theoretically, it is the first study to assess the validity of subjective interpretive constructs like rhetorical moves by analyzing the use of concrete linguistic features within and across those moves and revealing the connection between two ways that meaning is communicated in written texts. Pedagogically, this study may guide language teachers and materials designers in selecting texts and developing learning activities for English as a second or foreign language instruction. Insights from these analyses will help scientists who speak English as a second language to better understand and contribute to reports of scientific discoveries around the world.


Summer Institute in Chemistry and Physics for  Secondary School Teachers


Améliorer l'efficacité en santé et sécurité au travail au niveau du domaine minier

Social Sciences and Humanities Research Council of Canada

Canada Graduate Scholarships Program - Masters Scholarships

Univ. du Québec en Abitibi-Témiscamingue


Impact of Thalamic Impulses On Awake Neocortex


Identification and characterization of vitamin D3-regulated genes in head and neck squamous cell carcinoma


Evaluation capacity network:  aligning evaluative thinking and practice among early childhood stakeholders


GONOCOCCAL POR, OPA, AND NEUTROPHIL ACTIVATION


Neurophysiological Mechanisms Underlying Parkinsonian Motor Signs

PROJECT NARRATIVE Millions of people in the U.S. and worldwide have been diagnosed with Parkinson’s disease, a progressively debilitating disorder characterized by abnormal movement function. The goal of this study is to identify the specific changes in neuronal activity and connectivity between cortical and subcortical brain regions that are associated with the onset and progression of individual motor abnormalities associated with Parkinson’s disease. The results of this study will provide the understanding necessary for the refinement of current and development of future therapies, e.g. deep brain stimulation, transcranial magnetic and electrical stimulation and gene therapy, directed at modulating the neuronal activity in the basal ganglia-thalamocortical circuit responsible for the development of parkinsonian motor symptoms.


Canada Research Chair in Theoretical Condensed Matter Physics

No summary - Aucun sommaire


Development of the Blood Pressure Symptom Subdomain for the SCI-QOL

Spinal cord injury (SCI) is a lifelong condition, requiring care from multiple disciplines to diminish impairments, limit secondary complications, improve social functioning and quality of life (QOL). There are approximately 200,000 persons with SCI in the United States and 22% are veterans; the estimated annual cost to the VA for SCI health care is 2.14 billion. In recognition of the enormous expense associated with the long-term care of these individuals the VA supports and continues to fund research initiatives aimed at identifying optimal clinical practices for the care and management of SCI, by determining if clinical practices translate to improved outcomes and QOL (Quality Enhancement Research Initiative). The goal of this study is to develop a meaningful, relevant, and psychometrically sound tool to determine the impact of blood pressure dysregulation on QOL in persons with SCI.


Structured Protein Scaffolds for Phage-Display


Neural Activity Imaging and Sensing System Using Multifunctional Diamond Nanosens

! Health Relevance Research on neural circuitry is one of the primary drivers in the development of effective treatments and extends our understanding of neurological disorders such as mental disabilities, Alzheimer's disease, Parkinson's disease, and epilepsy. Mental disorders affect one out of every four Americans and cost the US economy over $100 billion a year, with depression being the leading cause of disability. Our program will put a new tool in the hands of neuroscientists aiming to unravel the complexities of neural networks and reverse engineer their circuits, which will accelerate the pace of discovery and lead to more effective treatments for neurological disorders.


Radical/Ion-Containing Block Copolymers: Self-Assembly and Application toward Organic Devices

A well-defined mesostructure of block copolymer templates was successfully functionalized with redox-active radicals and charge-compensating ionic groups via ionic liquid-assisted self-assembly. The obtained PS-b-PEO layer containing TEMPO-IL 1 exhibited morphology-driven modulation of charge-transport (on/off switching) in an organic thin film device. Location of radical and ionic molecules was correlated with resistive memory characteristics (rewritable/WORM, etc). We applied Kelvin Probe Force Microscopy (KPFM) technique and conductive AFM to visualize local surface potential and local conductivity change of microdomains under the programmed bias. Radical- and ion-functionalized block copolymers were also synthesized via controlled radical polymerization and ring-opening metathesis polymerization, and utilized as the active layer for organic memory.

Japan Society for the Promotion of Science


Routes of Congenital  Transmission of Avian Leukosis Viruses


Conscious awareness across time as a function of task and stimulus factors

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.


CLIN CTR CLIN TRIAL/OBSERVATIONAL STUDY OF WHI


Mitochondrial Oxidative Stress in Epileptogenesis

Project Narrative Temporal lobe epilepsy (TLE) is a prevalent form of acquired epilepsy often resistant to drugs and progressive in nature. Metabolic changes including mitochondrial dysfunction occur in TLE but how they contribute to its progression remains unknown. The goal of this project is to determine if a key function of mitochondria (reactive oxygen species) contributes to the development of epilepsy in animal models of TLE. Furthermore, the project will test the efficacy of drugs that are known to prevent mitochondrial dysfunction in TLE animal models.


Global QCD Analysis and Precision Electroweak Physics in High Energy Collider Phenomenology

This award funds the research activities of Professor C.-P. Yuan at Michigan State University (MSU).

Elementary-particle physics addresses the question of determining the smallest building blocks of matter.  Our current understanding is that protons and neutrons, and all other strongly interacting particles, are composed of fundamental particles called partons (quarks and gluons).  The strong interactions between the partons are described by the theory of Quantum Chromodynamics (QCD). In his research, Professor Yuan aims to develop theoretical methods to extract information from the QCD theory --- information which is critical for interpreting experimental data around the world, including data from recent experiments at the CERN Large Hadron Collider (LHC).  As a result, research in this area advances the national interest by promoting the progress of science in one of its most fundamental directions: the discovery and understanding of new physical law. This project is also envisioned to have significant broader impacts.  Professor Yuan will involve graduate students and postdocs in his research, and thereby provide critical training for junior physicists beginning research in this field. He also intends to give public lectures on his research results and develop new course curricula based on the results of his research.

More technically, Professor Yuan will extract the most updated CTEQ-TEA Parton Distribution Functions (PDFs) from a global analysis of the experimental data. (CTEQ is an acronym for "Coordinated Theoretical Experimental Project of QCD", and TEA for "Tung et al".) Professor Yuan will expand the theoretical capabilities of the analysis to include corrections from higher-order QCD interactions, heavy quark-mass effects, next-to-leading-order quantum electrodynamic (QED) interactions, and transverse momentum resummation.  He will also refine the techniques for analyzing the PDF uncertainties and the correlations among the predictions of various physical observables, and investigate the implications of PDFs and their associated uncertainties on the most important physical processes at colliders, particularly at the LHC.  Measurements of production rates for W, Z, top quark pairs, single top quarks and Higgs bosons  at the LHC --- including both inclusive rates and relevant kinematical distributions --- will provide major new input to the determination of PDFs during the next few years.  At the same time, refinements of the PDFs are crucial both for testing the Standard Model in greater precision and for probing New Physics effects at high-energy colliders.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.


Common Operations of Environmental Research Infrastructures

"Frontier environmental research increasingly depends on a wide range of data and advanced capabilities to process and analyse them.  The ENVRI project, “Common Operations of Environmental Research infrastructures” is a collaboration in the ESFRI Environment Cluster, with support from ICT experts, to develop common e-science components and services for their facilities. The results will speed up the construction of these infrastructures and will allow scientists to use the data and software from each facility to enable multi-disciplinary science.
The target is on developing common capabilities including software and services of the environmental and e-infrastructure communities.  While the ENVRI infrastructures are very diverse, they face common challenges including data capture from distributed sensors, metadata standardisation, management of high volume data, workflow execution and data visualisation. The common standards, deployable services and tools developed will be adopted by each infrastructure as it progresses through its construction phase.
Two use cases, led by the most mature infrastructures, will focus the development work on separate requirements and solutions for data pre-processing of primary data and post-processing toward publishing. The project will be based on a common reference model created by capturing the semantic resources of each ESFRI-ENV infrastructure.  This model and the development driven by the testbed deployments result in ready-to-use systems which can be integrated into the environmental research infrastructures.
The project puts emphasis on synergy between advanced developments, not only among the infrastructure facilities, but also with ICT providers and related e-science initiatives. These links will facilitate system deployment and the training of future researchers, and ensure that the inter-disciplinary capabilities established here remain sustainable beyond the lifetime of the project."


Development of spermatogenesis in captive-bred spix's yellow-toothed (Galea spixii, Wagler, 1831)

Fundação de Amparo à Pesquisa do Estado de São Paulo

Universidade de São Paulo (USP). Faculdade de Medicina Veterinária e Zootecnia (FMVZ)


Extracellular anomalies in Schizophrenia: from molecules to symptoms

The relevance of the proposed studies resides in their contribution to the understanding of the pathophysiological mechanisms of extracellular matrix abnormalities in schizophrenia and their relationships to the clinical manifestations of this disease. Investigations on neural and non-neural tissues accessible by biopsy will allow us to assess the potential validity of these abnormalities as clinically and pathophysiologically relevant biomarkers for schizophrenia.


Determining generic indicators of stress in eucalypt leaves for application to the remote sensing of canopy condition and productivity modelling

Biotic and abiotic stresses induce generic alterations of leaf chemistry (e.g. chlorophyll, anthocyanins). We will explore the behaviour of eucalypt leaf reflectance to changes in leaf cellular chemistry and structure arising from exposure to a range of stressful factors. We will relate leaf reflectance to physiological processes using a research radiation interception model. We will report on a) the potential integration of data related to stress, into process-based models for eucalypt plantation growth and b) the exploitation of generic reflectance indicators of stress in the remote acquisition of high resolution multispectral imagery with potential to spatially quantify plantation eucalypt health.


The ToxiFin Platform: Advancing High-Throughput Screening and Mechanistic Insights For Developmental Neurotoxicants Using the Zebrafish Model

NARRATIVE This research addresses the urgent need to assess the neurodevelopmental effects of chemicals on public health. By developing a high-throughput zebrafish screening platform, it offers a cost-effective and efficient alternative to conventional methods. Ultimately, the findings from this study have the potential to inform policies, enhance risk assessment, and guide the development of safer chemical alternatives, thereby reducing illness and disability associated with neurotoxic chemical exposures and promoting overall health and well-being.


Rôle de la dépression et du soutien à l’autonomie dans la pratique d’activités physiques chez des femmes ayant été traitées pour un cancer du sein.

La dépression diminue la motivation de faire de l’exercice. Les femmes atteintes de cancer du sein sont nombreuses à vivre avec des symptômes dépressifs, ce qui expliquerait en partie pourquoi elles sont moins actives et plus sédentaires que les femmes qui n’ont pas eu de cancer. Faire de l’exercice leur permettrait pourtant de diminuer les effets négatifs du cancer et de ses traitements (ex. : fatigue, douleurs, trouble de sommeil) et d’améliorer leur qualité de vie. L’équipe de soins peut aider les patientes à développer et à maintenir la motivation à faire de l’exercice en soutenant son autonomie (ex. : lui offrir des choix, ne pas lui mettre de pression, reconnaître ses émotions). 201 femmes montréalaises, qui ont récemment terminé leurs traitements pour un cancer du sein, ont été suivies pendant 5 ans. On a mesuré leur niveau d’activité physique et leur niveau de dépression et on leur a aussi demandé à quel point elles trouvent que leur équipe de soin soutient son autonomie. Mon projet vise donc à comprendre comment la dépression affecte la pratique d’exercice dans le temps chez les femmes qui ont reçu des traitements pour un cancer du sein et comment la relation avec l’équipe de soin peut aider ces femmes à changer leurs habitudes d’exercice. Les résultats de mon projet vont servir former les équipes de soins à mieux soutenir les femmes atteintes de cancer du sein dans la pratique d’activité physique et à adapter l’aide psychologique offerte à ces femmes selon l’évolution de leurs symptômes et de leurs besoins dans le temps.


瞬発系・持久系トップアスリートに特徴的な遺伝子多型・変異の同定と機能解析

オリンピアン等が有する類いまれな運動能力は、トレーニングといった本人の努力のみならず、生まれもった才能、つまり遺伝要因が影響している。運動能力を規定する機能的な遺伝子多型・変異が解明できれば、その遺伝子多型・変異が制御している遺伝子発現の増加や抑制を誘導させるトレーニング方法等の開発により運動能力の飛躍的向上が期待できる。本研究では、①トップアスリートの全ゲノム塩基配列の解析から瞬発系・持久系運動能力に関連する遺伝子多型・変異を同定し、②その遺伝子多型・変異によって調節される骨格筋や血液の遺伝子発現・生化学的な変化の検討から、運動能力に関連する遺伝子多型や変異の機能的役割を明らかにする。

Grant-in-Aid for Scientific Research (B)


Targeting histone methyltransferase EZH2 for the treatment of hematological cancer

PROJECT NARRATIVE This project aims to develop and validate a novel pharmacological agent for targeting the function of Enhancer of zeste homolog 2 (EZH2; a highly attractive anti-cancer drug target), which can overcome limitations of the currently available enzymatic inhibitor of the same protein. By employing the cutting-edge PROTAC (stands for “proteolysis targeting chimeras”) technology, we have already identified a highly promising PROTAC lead compound; we will further determine the effects of this lead EZH2-targeting small-molecule in the inhibition of tumor cell growth in mouse models as well as define its molecular effects by using integrated genomics profiling technologies. Results of this project are expected to establish a promising preclinical strategy for the treatment of hematological cancer patients displaying very poor clinical outcomes.


Cardiovascular Cell Therapy Research Network


魚肉中のアレルゲンの性状解明

1. メバチなどの抽出液中にパルブアルブミン(PA)とは異なる新規アレルゲンの存在を確認した。このアレルゲンは,本研究室にプールされた日本人の魚アレルギー患者5名中3名もの血中IgEに対して反応陽性であったことから,日本の患者に対して特有なものではなく,かなりの数の患者のIgEが反応する可能性が考えられた。2. 新規アレルゲンの精製,同定を試みたが,従来の手技に従った各種クロマトグラフィーの組み合わせのみでは精製が非常に困難であることがわかった。クロマトグラフィーのステップを変更しても,精製の途中で新規アレルゲンは再現性なく複数のピークに分かれてしまうことから,透析,凍結乾燥などの操作も含め,操作中に何らかの変性を受けるものと判断された。なお,SDS-PAGEによる推定分子量は100k以上であった。3. 市販の魚肉練り製品(かまぼこ,はんぺんなど)のアレルゲン性をELISAで検討した。その結果,冷凍すり身が主原料である加工品に対し,反応陰性と陽性の血清とに二分された。製造工程のうちの水晒しのモデル系でPAの減少を確認した。よってPAのみに反応するIgE保有患者にとって,これらの加工品は低アレルゲン化が実現されていることを明らかにした。一方,新規アレルゲンは水晒し工程では除去できず,陽性血清はすべてこれに対する血中IgE保有者のものであった。また,冷凍すり身未使用のものではPAの残存する製品も見い出され,練り製品が魚アレルギー患者に対して必ずしも安全というわけではないことをin vitroで証明した。4. 新規アレルゲンの精製方法をさらに検討している。これまでの種々の検討から,本新規アレルゲンは筋肉構成タンパク質である可能性も考えられ,既報の筋原線維タンパク質の精製方法も応用して,アレルゲンの精製,同定に努めている。

Grant-in-Aid for Encouragement of Young Scientists (A)


Advancing M&A Research with a Novel Dataset on Post-Acquisition Integration: Performance and Innovation Implications

Post-acquisition integration is the process of aligning operations, structures, and routines between the acquiring and target firms after an M&A deal is closed. While integration can unlock synergies and long-term value, it can also disrupt established practices and create internal resistance. Although post-acquisition integration has been the object of many studies in corporate strategy (e.g., Barkema & Schijven, 2008; Graebner et al., 2017; Larsson & Finkelstein, 1999; Zaheer et al., 2013), data availability and measurement challenges have hindered empirical analysis both on the role of post-acquisition integration in shaping the outcomes of M&A activities (e.g., performance, innovation output) and on the key drivers that lead to the decision to integrate a target firm (e.g., quality or business of the target firm). Studies based on surveys-based measures offer rich but small-scale insights that are subject to generalizability issues. Studies focusing on media-based proxies offer a more scalable measure of post-acquisition integration, but they typically rely on blurred signals of integration occurrence. Overall, the academic community still lacks a comprehensive dataset that can measure post-acquisition integration on a large scale. Thus, this study aims to develop an open-access dataset to measure post-acquisition integration, revisit one of the core findings in M&A research (i.e., the influence of post-acquisition integration on acquisition performance), and explore post-acquisition integration role on firms’ innovation capacity.Subproject #1 primarily aims to develop an open-access dataset of post-acquisition integration by leveraging two existing datasets: SDC Platinum and the National Establishment Time Series (NETS). To do so, it will track structural changes in the acquiring and target firms—such as closing or relocating facilities, reassigning workforces, and restructuring revenue flows—before and after the deal closing. The expected outcome is a dataset of measures of post-acquisition integration covering nearly 190,000 deals in the US from 1989 to the present, representing ~65% of all deals included in the SDC database during the examination period. Subproject #2 utilizes the resulting dataset to revisit one of the core debates in M&A research: Does higher integration necessarily lead to better acquisition performance, or does it destroy value? Under what boundary conditions? Prior studies report mixed findings, highlighting both the benefits of synergy and the potential erosion of routines and key personnel. This subproject will test, on a large scale, whether integration is beneficial on average and under what conditions it is more beneficial—such as organizational similarity or prior M&A experience.Subproject #3 narrows the analyses to the pharmaceutical sector (included in the database of Subproject #1) and explores another key question in M&A research (Paruchuri et al., 2006; Puranam et al., 2006; Valentini, 2012)-i.e., how integration practices influence firms’ innovation capacity. The pharmaceutical sector is an ideal setting to explore the connection between M&A and innovation due to the prominent role of M&A activities in an industry that is heavily dependent on innovation (e.g., pipeline management). By linking the new integration metrics with drug development data, this subproject aims to assess whether specific integration strategies improve R&D outcomes, accelerate clinical trials, raise approval success rates, or stifle promising projects through overly aggressive restructuring.

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

Università della Svizzera italiana – USI


AFRICAN AMERICAN STUDY OF KIDNEY DISEASE


Regulatory mechanisms of intussusceptive (splitting)  angiogenesis and their potential clinical implications

 that mononuclear cells are involved in intussusceptive microvascular growth and that they are likely of bone marrow origin.Our preliminary data obtained from human cancer patients treated with VEGF inhibitors indicate that the switch from sprouting to IA could represent an escape mechanism also in humans accounting for the development of resistance to antiangiogenic treatment. Another important finding is  In the last period we demonstrated that IA permits a rapid expansion of the capillary plexus and plays an essential role in the vascular remodeling and angioadaptation during normal and pathological angiogenesis. Our recently obtained data indicate that, during normal development and in the regenerative stages of nephritis and after partial liver resection, IA is essential for formation and restoration of an organ-specific angioarchitecture. In addition, IA plays an import role as a “escape” mechanism during and after irradiation and anti-VEGF therapy. short history, and we are only now beginning to understand its significance. Intussusceptive angiogenesis has a

novel insights in the regulation mechanisms of IA and translate the findings to clinically relevant topics as tissue regeneration and tumor growth. During the next 3 years we will focus on the following fundamental aspects: i) Blood flow and shear stress as regulatory mechanisms of IA. ii) Genetic predetermination of IA, especially the role of Notch pathway and associated with it EphrinB2/EphB4, α-SMA and Tie-2 signaling. iii) The role of the bone marrow derived stem cells in the IA during tissue regeneration and their contribution to the “escape” mechanism after anti VEGF therapy and irradiation in cancer. is to obtainThe aim of the current project

 e repair, and in tumor angiogenesis. Our data will help us to design more effective pro- and anti-angiogenic treatment strategies.We anticipate that this project will yield important information relating to the role of intussusceptive angiogenesis in the embryonic development, in tissu


Social Sciences and Humanities Research Council of Canada


Annual plan for the implementation of the resources of institutional technical reserve for the renewal of research infrastructure of the School of Public Health - USP, 2016

The Faculty of Public Health, University of São Paulo discussed the implementation of RTI FAPESP 2016 in its various instances. Three departments and the information technology section, this board linked to the FSP, presented their proposals for discussion by members of the Unit of Research Commission which prepared a single plan for the implementation of resources. The plan was submitted to the Congregation for the examination by Mr. members of the Board. Four proposals were approved. The first was presented by Section of Information Technology by the Director of FSP-USP. This was considered a priority, as it will meet students, professors and staff servers in its entirety. The second proposal was presented by the head of the Department of Epidemiology and approved, as will favor the modernization of physical infrastructure occupied by faculty, graduate students and postdocs department. The third proposal was submitted by the head of the Department of Maternal and Child was adopted. The amount requested is small, but the equipment. air conditioning, which will be installed in both enclosures are necessary since they become the most suitable and healthy environments, especially during periods of higher temperature, which undoubtedly is compounded by the use of electronic equipment that generates heat. The fourth proposal was presented by the head of the Department of Nutrition and is part of the renewal plan of laboratories that department. This will be the final stage, as two other proposals for the renewal of these laboratories were provided with RTI resources in previous years. (AU)

Auxílio à Pesquisa - Reserva Técnica para Infraestrutura Institucional de Pesquisa

Universidade de São Paulo (USP). Faculdade de Saúde Pública (FSP)


Nasopharyngeal Microbiome and Risk of Bacterial Pathogen Colonization in Infants

PROJECT NARRATIVE This Mentored Patient-Oriented Research Career Development Award will support didactic and practical training activities in bioinformatics and computational biology for Dr. Matthew Kelly, as well as research to understand how naturally occurring bacteria in the upper respiratory tract impact the risk of colonization and invasion by bacteria that cause pneumonia in children. Findings from this clinical study, involving mother-infant pairs in Botswana, may provide a basis for the development of rationally-designed probiotics that can prevent pneumonia and other respiratory infections.


Cellular Biology Of Host/parasite Interactions

NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Neoropeptide Basis of Social Loss and Depression


NORPLANT EFFECT ON CARDIOVASCULAR RISK IN YOUNG WOMEN


Sugar Salem School/Community Library - to expand public access to computers and the Internet


Omics, mice, and men: Development of precision transfusion medicine

In this study we test a novel hypothesis that inherited variability in genes of red blood cell proteins significantly modulate RBC function and recovery after transfusion. We will explore how donor genotype determines the time limits of blood storage and recovery of cells after storage, to identify super donors versus fragile donors.


GENOMIC ANALYSIS OF INHERITED BREAST AND OVARIAN CANCER

PUBLIC HEALTH RELEVANCE: The goal of this project is characterize the whole genomes from severely affected breast and ovarian cancer families to identify new clinically actionable mutations so that they can be incorporated into clinical care. DNA and RNA samples from women with breast and ovarian cancer and their tumors will be sequenced. Mutations will be evaluated with respect to function and relative risk of breast and ovarian cancer.


Glucocorticoids & adipocyte function in human obesity

PUBLIC HEALTH RELEVANCE: Obesity increases risk for many chronic diseases, including type 2 diabetes, and thus is a major public health problem. People who store more fat inside the abdomen are at greater risk for obesity-related diseases. This proposal will lead to a deeper understanding of how fat distribution is controlled.


The Safety and Impact of Expanded Access to Naloxone in Health Systems

PROJECT NARRATIVE Opioid overdoses have reached epidemic proportions in the United States. Our study will examine the impact and safety of expanded access to naloxone, an effective opioid antidote which reverses opioid overdose, for patients prescribed opioids for pain in two large and diverse health systems. This research will address key evidence needs about expanded access to naloxone to HIV and other primary care practices.


レーザーコンプトン散乱の精密測定による加速電子偏極度測定法の開発

Principal Investigator：鈴木 史郎, Project Period (FY)：1978, Research Category：Grant-in-Aid for General Scientific Research (C), Research Field：核・宇宙線・素粒子

Japan Society for the Promotion of Science


Bioengineering Approach for Advancing Reparative Medicine Stem Cell Technologies

Project Narrative Adipose derived stromal vascular fraction (SVF) transplantation is a promising new therapy for applications spanning from cardiac ischemia to tissue repair based on the idea that SVF can form new vessels. This proposed work will develop a new technology that enables the discovery of SVF dynamics in a real perfused microvascular network environment. Understanding where and how SVF cells contribute to microvascular growth will help guide their therapeutic use.


Was ist der Einfluss stellarer Konvektion auf die Detektierbarkeit kleiner Planeten mit der Radialgeschwindigkeitsmethode?

Eine wesentliche Richtung der Forschung im Bereich extrasolarer Planeten ist die Suche nach kleineren und leichteren Planeten. Diese Suche wird derzeit mit neuen und geplanten Instrumenten massiv vorangetrieben. Bei der Genauigkeit, die mit diesen Instrumenten und der Radialgeschwindigkeitsmethode erreicht werden kann, spielen konvektive Prozesse (jitter), deren Auswirkung im Bereich m/s liegt, eine entscheidende Rolle. In diesem Projekt wird ein entscheidender Schritt gemacht zum Verständnis des Einflusses konvektiver Prozesse auf die Messung von Radialgeschwindigkeiten, insbesondere wie dadurch die Detektierbarkeit extrasolarer Planeten beeinflusst wird, und wie dieser Mechanismus bei der Suche nach immer leichteren Planeten berücksichtigt werden kann. Die Ergebnisse dieser Arbeit liefern grundlegende Erkenntnisse zur Maximierung des wissenschaftlichen Nutzens laufender und zukünftiger Radialgeschwindigkeitsprogramme zur Suche nach extrasolaren Planeten.


PROSTATE CANCER SCREENING PROGRAM FOR AFRICAN AMERICAN M


STUDIES OF CHEMICAL DISPOSITION IN MAMMALS


Wirkungen tiefer Hirnstimulation auf Sprech und Sprachfunktionen

Während die tiefe Hirnstimulation (THS) die Primärsymptome verschiedener Bewegungsstörungen positiv beeinflusst, wurden heterogene und somit weniger kalkulierbare Veränderungen von Sprech-und Sprachleistungen unter dieser Therapie beobachtet. Diesem Problem nähert sich das folgende Projekt auf unterschiedlichen Ebenen. Aufbauend auf Vorarbeiten der Antragsteller soll mit neurophysiologischen, psychometrischen und behavioralen Methoden untersucht werden, ob und welche Funktionen THS-Zielregionen in der Verarbeitung von Sprache haben. In Kooperation mit den Projekten 3, 8 und 9 des Gesamtantrags sollen dadurch einerseits klinisches Optimierungspotenzial der Methode identifiziert bzw. perspektivisch ausgeschöpft werden und andererseits neuroanatomische und funktionelle Modelle kortiko-basaler Sprachverarbeitung fortentwickelt werden.


Modélisation multi-échelle du comportement différé des géomatériaux anisotropes

This proposal is devoted to experimental investigation and numerical modelling of time dependent behaviour of geomaterials, in particular anisotropic rocks materials. The initial anisotropy of such materials is generally related to the presence of initial defeats such as bedding planes, fractures and cracks. During ulterior loading, the initial defeats can evolve and new micro-cracks can develop and grow, leading to microstructure change of materials. These microstructure evolutions can modify the anisotropic nature and significantly affect macroscopic properties of materials. It is then necessary to develop suitable modelling in order to account for microstructure evolution and interaction between initial and induced anisotropies. Moreover, the microstructure evolution is also origin of time dependent behaviour of material. In classical investigations, the time dependent behaviour is generally described by viscoplasticity theory; this approach provides an efficient mathematical tool to deal with time dependent deformation, but can not properly take into account physical origins involved. Indeed, in a number of cases, the viscosity is not the unique origin of time dependent deformation; other important phenomena can exist, such as sub-critical propagation of microcracks with stress corrosion, dissolution of inter-granular contact areas by pressure solution process. In the present project, it is proposed to deal with two complementary features: laboratory testing and in situ investigation in order to identify different phenomena which are origin of time dependent deformation; and develop a multi-scale approach for numerical modelling by including the identified mechanisms. Two representative rocks, sedimentary rock and poly-crystal rock, will be selected in this work. The present proposal will deal with three jointed features: experimental characterization of different mechanisms responsible to time dependent behaviour and determination of overall creep deformation in laboratory and in situ; development of multi-scale and multi-physics approach for numerical modelling; numerical implementation, validation and application. These features will be organized in 8 tasks, which are described in detail in the research program: ? Task 1: experimental characterisation of phenomena; ? Task 2: experimental investigation of chemomechanical coupling; ? Task 3: characterization of overall time dependent deformation; ? Task 4: in situ experimental in situ; ? Task 5: formulation of a basic constitutive model for instantaneous mechanical behaviour of rocks ? Task 6: extension of the basic model to time-dependent behaviour; ? Task 7: consideration of chemomechanical coupling; ? Task 8: numerical implementation and validation.


The genetics of bacterial evolution and biodiversity

The aim of the project is to significantly advance and deepen knowledge of the mechanisms driving evolution and biodiversity in the bacterial kingdom. Bacterial evolutionary change is traditionally explained by the combined effects of mutation and horizontal gene transfer events. However, analysis of the ongoing flood of bacterial genomic data has revealed at least two features of bacterial chromosomes that appear to be discordant with the standard model of genetic change. These are, the recent discoveries of bacterial strains with hybrid chromosomes, and the prevalence of chromosomal gene order rearrangements between bacterial species, neither of which is easily explained by the traditional model. By combining experimental and in silico approaches the project will explore hypotheses to explain the mechanisms driving these changes, their relevance in clinical and natural isolates, and the genetic and environmental features that influence the rates of change associated with these mechanisms. The outcomes will influence our understanding in several important areas, including evolution of virulence and antibiotic resistant pathogens, and the processes of lineage separation and speciation in bacteria. This project concept is highly original and could fundamentally expand our understanding of mechanisms and rates of bacterial evolution.


GEMS, a Short-Term Summer Internship Program for Diverse Students

This short-term internship program at the University of Colorado Anschutz Medical Campus, locally known as GEMS (Graduate Experiences for Multicultural Students) seeks to expose undergraduate and health professional students from backgrounds under-represented in research to summer laboratory or clinical translational experiences in order to increase their representation in research related to cardiovascular, pulmonary or hematologic areas. The goal is to create a workforce of health-related researchers who are as diverse as the community they serve. By exposing these students early in their careers, we hope to capture their interest and excite them about the possibilities of biomedical research.


EVALUATION OF POLICY-RELATED RESEARCH IN THE FIELD OF  MUNICIPAL SYSTEMS, OPERATIONS, AND SERVICES-FRANCHISING AND REGULATION


INNATE IMMUNE RESPONSES TO MALARIA PARASITE


Understanding the origin,initiation,and progression of high-grade serous ovarian

PUBLIC HEALTH RELEVANCE: Currently no diagnostic test or screening can detect ovarian cancer early enough to reduce the mortality. The lack of effective early detection is primarily because the early tumor biology of deadly ovarian cancer has been largely unknown. The proposed research will help improve our understanding on the early tumor mechanism and progression of this deadly cancer, which will offer valuable insights for developing effective earl detection and targeted therapy.


Flexible and sustainable production of high performance rolling bearings

Purpose and goal:
The project aims to increase the production flexibility for the manufacturing of large sized bearings by reducing the number of process steps and improving the properties of the components by using a novel hard turning (HaT) strategy. This will be realised by develop and potentially develop a methodology to qualify the hard-turning process as a finishing process. This strategy will generate a unique high-strength metallic surface, which will improve the surface mechanical properties hence the life of the bearings.

Expected results and effects:
The project aims to improve the manufacturing of bearings which will both enable prolonged life of the bearings as such but also allows for reducing the manufacturing leadtime, the energy consumption and enable mass customization enabled by the HaT process.

Approach and implementation:
TURN2FLEX will be operating in three major phases; Phase 1 involves carrying out the machining tests at Sumitomo in Germany to set the machining conditions. In Phase 2, the tests performed in Phase 1 will be validated at the research centre at SKF. In Phase 3, the machining tests will be carried out in a machining centre resembling similar condition as the production to evaluate the process robustness. All the characterization of the produced parts will be performed by Chalmers and RISE. The mechanical tests will support to reach the set goal with respect to surface integrity properties.


Integrated Antimicrobial Drug Discovery Scheme for Multidrug Resistant Bacteria


Producing experts, practicing expertise:  an ethnographic study of lactation consultation

Social Sciences and Humanities Research Council of Canada


No summary - Aucun sommaire

Natural Sciences and Engineering Research Council of Canada

University Undergraduate Student Research Awards


Research for development of therapy of Machado-Joseph disease by siRNA

Machado-Joseph disease is a progressive heredodegenerative disease that is caused by unstable expansions of CAG repeats in MJD which is located at chromosome 14q32.1. The mutant ataxin-3, the gene product of MJD, carrying the expanded polyglutamine stretch gains an adverse function and causes dysfunction of neurons, leading to neuronal death. No effective therapeutics has been established. If the expression of the mutant protein could be inhibited, we could treat the disease very well. Short interfering RNA (siRNA) would be a good candidate to establish an effective therapeutics.Huntington's disease is also one of the polyglutamine diseases and cased by an abnormally expanded CAG repeats in exon 1 of the HD gene. It was investigated that the effects of siRNAs directed against the HD gene in order to knock down its expression in cultured cells. One siRNA, named as siRNA-HD-Exon1, which is targeted against the region at immediate upstream of the CAG repeats, can efficiently and specifically inhibit the expression of HD exon 1-EGFP fusion mini-gene. It also did efficiently suppress the endogenous huntingtin expression in cultured cell lines derived from human neuroblastoma (Proc Japan Acad 79(Ser B) : 293-298, 2003).There are several single nucleotide polymorphisms (SNPs) in the MJD gene. In Japanese population, there are two haplotypes of those SNPs. One is c527T-c669A-c987C-c1118A and the other is c527C-c669G-c987G-c1118C.Disease chromosomes which carry the abnormally expanded CAG repeats show exclusively the former haplotype. If the expression of the allele carrying that haplotype could be specifically and effectively inhibited by a suitable siRNA, it would be the first step toward the development of a radical therapy for MJD. Two research groups reported successful suppression of the haplotype-specific expression by the siRNA of which the target is the sequence surrounding c987C/G SNP.

Japan Society for the Promotion of Science


Geriatric Oncology: Cognition and Communication

Project Narrative This cancer education training project’s goal is to train healthcare providers (HCPs) to work more effectively with older cancer patients who may have cognitive and functional difficulties. This project is important because it will help prepare the work force to care for the growing numbers of older cancer patients and their families. Results of this study have the potential to improve the knowledge and communication skills of oncology HCPs which will benefit HCPs and older oncology patients and their families.


STRUCTURAL PROPERTIES OF GROUP 1, 11, AND 111  ORGANOMETALLIC COMPOUNDS


Collaboration internationale en Chimie : origines des anomalies thermodynamiques et dynamiques de l'eau liquide métastable

Water is among the most important and most studied substances on earth, yet, the origins of its anomalous thermodynamic, dynamic, and structural properties have eluded complete understanding. Theoretical, computational, and experimental work suggests that clues to these origins lie in the metastable states of water at negative pressures (stretched superheated regime) and at supercooled temperatures. This collaborative proposal brings a broad, new set of techniques to bear on the challenge of providing a complete, experimental analysis of these states. The outcomes of this project will build the foundation of improved understanding of water and will provide a rich training ground for students in experimental physical chemistry. Outstanding questions: Q1) Phase diagram and structure in the stretched superheated and supercooled regimes. The equation of state has never been mapped deep into these regimes, leaving open fundamental questions about features that could explain the anomalous properties of water. Computational studies indicate a tight correlation between the evolution of molecular structure and macroscopic anomalies. The minimal experimental data on structure in the streched superheated regime leave open important questions regarding the accuracy of these predictions and the energetics (enthalpy vs. entropy) that may dictate these phenomena. Q2) Mechanisms of failure of metastable states. In all but one experiment, the observed stability limit in the stretched superheated regime has been several fold lower than predicted theoretically. Recent experiments by Caupin suggest that there may exist a fundamental mechanism of nucleation that is not accounted for in conventional predictions; the elucidation of this mechanism would have profound scientific and technological implications. Q3) Viscosity in the supercooled regime. Only one reliable experiment is available at 1 bar in the supercooled regime; none exist in the streched superheated regime. These measurements, combined with existing diffusivity data, will allow to check the Stokes-Einstein and Stokes-Einstein-Debye relations, thought to be violated in water at higher temperatures than usual glass forming liquids and to provide a signature of the liquid-liquid critical point predicted by simulations in the supercooled region.


A murine model to investigate the mechanisms underlying DOHaD

Recent studies have clearly established a relationship between sub-optimal intrauterine and post-natal development, and later life predisposition to adult disease, including type II diabetes, hypertension, heart disease, stroke and other neurologic disorders a relationship termed "developmental origins of health and disease" (DOHaD). While adverse pre- and postnatal development increases the risk of DOHaD it does not determine that an individual will acquire these disorders suggesting that interactions between an individuals genotype and the environment may contribute to the eventual outcome. Increasing evidence suggests that premature activation of the fetal hypothalamic-pituitary-adrenal (HPA) axis is a central component linking adverse pre and/or post-natal environmental exposures to later poor health outcomes. We have developed a novel mouse model in which dietary restriction of the mothers during pregnancy leads to symptoms of DOHaD disorders in the offspring. We will use this model to define gene-environment interactions that result in DOHaD disorders. We anticipate that this study will enhance progress towards future intervention strategies aimed at reducing the burden of these disorders.

Lunenfeld-Tanenbaum Research Institute (Toronto)


Improving Health Care for Women Veterans:  Addressing Menopause and Mental Health

Advancing comprehensive care for women Veterans is a VA priority, as the number of women Veterans served by the VA has doubled in the past decade and continues to grow rapidly. However, providing gender-sensitive care in this setting is a recognized challenge. Women Veterans have complex care needs, complicated by reproductive health concerns and a high rate of mental health diagnoses. Menopausal symptoms common in this period may contribute to mental health concerns in addition to poor quality of life, health risk behaviors, and chronic health conditions. An estimated half of women Veterans VA users may currently be affected, but little is known about the experience of menopause among women Veterans, or current practices and preferences for menopause-related care among patients and providers in the VA setting. Innovative efforts to increase access to gender-sensitive menopause-related care for women Veterans may provide an opportunity to improve whole health for this population, and healthy aging in the years that follow.


STRUCTURAL AND FUNCTIONAL BASIS OF THE VITAMIN K CYCLE

PROJECT NARRATIVE The proposed research is relevant to public health because VKOR is the target of warfarin, the most commonly prescribed oral anticoagulant. Warfarin is used to treat and prevent thrombosis diseases including deep vein thrombosis, pulmonary embolism, stroke, and myocardial infarction. Understanding the mechanism of VKOR function and warfarin inhibition will help to produce clotting factors to treat bleeding disorders and to design better anticoagulants.


Enhancing motor competence, health-related fitness, and psychosocial wellbeing among children with motor difficulties – A cluster-randomized controlled trial (MoDiSchool)

This study focuses on helping school-aged children with motor difficulties by improving early recognition and support. In the first phase, we will explore how these challenges can be identified using input from children (n=1200), parents (n=1200), and teachers (n=510). We will combine standardized tests, and children's, parents' and teachers' reports to assess motor difficulties and compare the results of different methods. We will also examine teachers' competencies to support motor skill development. In the second phase, we will test a 20-week physical activity intervention program. The study will involve three groups: classroom activities only, classroom and extracurricular activities, and a control group. Outcomes include physical and psycho-social variables, with follow-ups at 5 and 12 months. Teachers will co-design the program to ensure it fits well in schools. Study results can be widely used in schools and teacher education.

Academy Programme for Sport Science and Physical Activity (ACTIVE) 2025 call for applications


腐蝕性根管消毒剤の生体に対する為害性に関する研究

Principal Investigator：藤正 敬夫, Project Period (FY)：1982 – 1984, Research Category：Grant-in-Aid for General Scientific Research (B), Research Field：Conservative dentistry


DEFENSE & STATE MEMORANDUM OF AGREEMENT - COOPERATIVE AGREEMENT

STATE MEMO OF AGREEMENT PROGRAM FOR THE REIMBURSEMENT OF TECHNICAL SERVS


Salmonella pathogenicity island 2 effector proteins


No description available


Lipid Aldehyde and Ethanol Induced Liver Damage


The study to reveal the neuroprotective mechanisms induced by electrical stimulation of the brain

We tried to reveal the neuroprotective mechanisms induced by the electrical stimulation of cerebellar fastigial nucleus (FN) in rats. 1h-FN stimulation decreased, 72h later, the infarct volume by 22%. 1h-FN stimulation increased, 72h later, mRNA level of uncoupling protein 4 (UCP4), a mitochondria protein, to 160% in the brain. Intra-ventricular injection of siRNA decreased the UCP4 mRNA level, and tended to abolish the neuroprotection induced by FN stimulation. Following FN stimulation, up-regulation of UCP4 may be a component of the endogenous neuroprotective mechanisms.


Paracrine and synaptic mechanisms underlying recovery using human stem cell thera

PUBLIC HEALTH RELEVANCE: Stem cells therapy offers hope to the millions of stroke patients in the US who live with its debilitative effects. With its devastating long-term consequences to patients and their families, and the tremendous societal costs in the billions of dollars each year, the implications of a successful treatment for stroke are enormous. Because stem cells target brain repair and thus can have a therapeutic effect months or even years post-injury, their use as a stroke treatment has the potential to impact a vastly larger proportion of te patient population than current therapeutic strategies.


Proposed Meeting Series:  The Message Passing Interface Forum

The work of the proposed Message Passing Interface Forum addresses the continuation of activity focused on enhancing the Message Passing Interface (MPI) for passing data between processors in distributed computing systems built from heterogeneous multi-cores, for parallel remote file operations, and for dynamic process control of such parallel applications. The current standard provides a core of routines used for point-to-point and one-sided data exchange, blocking collective communications routines, remote parallel file access and dynamic process control. In addition, these are augmented with support for features such as derived data types, communications contexts, process groups, and virtual process topologies.
The work of this forum will produce a communications standard suitable for addressing the needs of parallel applications on the next generation computing facilities at the petascale level and beyond.


Defining the Role of ERG in Modulating the AR Cistrome and Antiandrogen Sensitivity

PUBLIC HEALTH RELEVANCE: Over half of prostate cancer cases are caused by chromosome translocations that result in aberrant expression of the ERG transcription factor. This project will shed light on the molecular mechanisms by which ERG causes prostate cancer and the impact of ERG on response to therapies directed against the androgen receptor, the common form of treatment for metastatic prostate cancer.


Mechanisms Regulating Megakaryocyte Development

Megakaryocytes (MKs) are responsible for the production of platelets, which have a major impact on blood homeostasis. MKs is unique among blood cells in attaining states of polyploidy, which precedes platelet biogenesis. Uncontrolled MK proliferation and deregulated polyploidization are hallmarks of blood cells pathology, and this research proposal focuses on novel aspects of regulation of MK expansion and polyploidization, involving Lysyl Oxidase (LOX) as a newly identified regulator of these processes.


Bariatric Surgery's Return on Investment for Veterans and VHA

The proposed study examines weight change after bariatric surgery, the resolution of diabetes,  hypertension, and hyperlipidemia, and the durability of weight change and disease resolution by  follow patients over an entire decade of care (2000-2012). The long-term durability of these  health improvements have been poorly characterized in the literature. We will also identify  patient-level characteristics that are associated with failures - failures to lose weight, failures to  resolve comorbidities, and failures to achieve long-term weight maintenance - in an explicit  attempt to identify important factors associated with less desirable health and economic  outcomes. These new areas of inquiry will address important limitations of our initial work and  the existing bariatric surgery literature.


Neighborhood Effects on Health and Functioning of Elders


A COMPARISON OF THREE APPROACHES TO SUPPORTED EDUCATION


Midcareer Mentoring Award for Patient-Oriented Research in Aging

PUBLIC HEALTH RELEVANCE: With this K24 award, Dr. Rachel Werner will continue to develop her successful research program aimed at improving the delivery of care for older patients with complex and chronic illness, with a new focus on the  implementation and evaluation of delivery system innovations using randomized trials. She will use her research as a platform to mentor new investigators in this field and help them to become independent investigators. Taken together, her ongoing and proposed research, coupled with her mentorship program to train outstanding investigators in the field, will help address the critical need to reform the health care delivery system to efficiently bring high quality care to the millions of aging Americans in need of better care.


Optics For Pre-College Science Teachers and Scientists


RETINAL DISEASE: MOLECULAR BASIS AND PATHOPHYSIOLOGY


Biomechanical Optimization of TE Heart Valves


Cell physiological and molecular biological mechanisms of the function of the stria vascularis in the cochlea

Intermediate cells are melanocytes in the stria vascularis. To examine the contribution of the membrane potential of intermediate cells (E_m) to the endocochlear potential (EP), a comparison was made between the effects of K^+ channel blockers on the E_m and those on the EP. The E_m changed by 55.1 mV per ten-fold changes in extracellular K^+ concentration. Ba^<2+>, Cs^+ and quinine depressed the E_m in a dose-dependent manner, whereas tetraethylammonium at 30 mM and 4-aminopyridine at 10 mM had no effect. To examine the effect of the K^+ channel blockers on the EP, the EP of guinea pigs was maintained by vascular perfusion, and K^+ channel blockers were administered to the artificial blood. Ba^<2+>, Cs^+ and quinine depressed the EP in a dose-dependent manner, whereas tetraethylammonium at 30 mM and 4-aminopyridine at 10 mM did not change the EP. The changes in the EP were similar to those seen in the E_m On the basis of these results, we propose that : the EP is critically dependent…Moreon the voltage jump across the plasma membrane of intermediate cells.The intercellular space in the stria vascularis (intrastrial space) is a closed space and isolated from both the endolymph and the perilymph in normal tissue. Loop diuretics such as bumetanide and furosemide cause an acute enlargement of the intrastrial space in association with a decline in the endocochlear potential. It is known that bumetanide inhibits the Na^+-K^+-2Cl^- cotransporter, which is expressed abundantly in the basolateral membrane of marginal cells. We studied ionic mechanisms underlying the bumetanide-induced enlargement of the intrastrial space using perilymphatic perfusion in guinea pigs. Perilymphatic perfusion with artificial perilymph containing 100 μM bumetanide caused marked enlargement of the intrastrial space, as reported previously. Removal of K^+ from the perilymph did not affect the bumetanide-induced enlargement, whereas removal of Na^+ from the perilymph inhibited it almost completely. Perilymph containing 1 mM amiloride also inhibited the enlargement of the intrastrial space almost completely. These results indicate that perilymphatic Na^+, but not K^+, and amiloride-sensitive pathways are essential to the bumetanide-induced enlargement of the intrastrial space. Two possible pathways could yield these results. Na^+ in the perilymph could enter the endolymph via Reissner's membrane or the basilar membrane ; Na^+ in the endolymph would then be taken up by marginal cells via the apical membrane and secreted into the intrastrial space by Na^+-K^+-ATPase in the basolateral membrane of them. Another, less likely, possibility is that Na^+ in the perilymph is transported into basal cells or fibrocytes in the spiral ligament, then into intermediate cells via gap junctions, and finally secreted into the intrastrial space via Na^+-K^+-ATPase of intermediate cells.Less

Japan Society for the Promotion of Science


Regulation of Cellular Cholesterol Homeostasis

PUBLIC HEALTH RELEVANCE: Lipid homeostasis is essential for cell function and disruptions to lipid homeostasis lead to common diseases that are public health imperatives in the United States. Elevated serum cholesterol is a primary risk factor for heart disease, and diabetes causes fatty liver that frequently progresses to liver cirrhosis and cancer. This proposal seeks to understand the function and regulation of the SREBP transcription factors that control lipid homeostasis, thereby identifying new points for prevention and therapeutic intervention for these widespread diseases.


Managing Digital Data Collections for the Earth & Ocean Sciences:  Geoinformatics for Geochemistry and the Marine Geoscience Data System

Intellectual Merit:  This research combines major geochemical database operations for the marine geosciences at the Lamont Doherty Earth Observatory of Columbia University into a fully integrated management system called the Geoinformatics for Geochemistry Program. The work allows the combined efforts to build on substantial synergies between the presently disparate efforts.  It will enhance interoperability of the present web accessible database and allows the program to achieve both sustainability and economies of scale in terms of staffing, education and outreach, and staffing.

Broader Impacts: Broader impacts of the work are to enhance the infrastructure for research in the marine geosciences and allow fundamental new understandings in the Earth and Ocean Sciences due to the ease of combining and visualizing various disparate data sets.  The new management structure allows universal public and scientific access to global data compilations that support research and education in the Earth and Ocean Sciences.

Columbia University Lamont Doherty Earth Observatory


Epidemiological features, national burden of several HPV-related diseases and estimation of cost-effectiveness of HPV vaccines in Vietnam

This project is designed to collect the evidence that will be needed to support the introduction of the cancer-preventing vaccine HPV (Human Papillomavirus) into the national immunization program of Vietnam. HPV is the second vaccine that has been developed that can prevent cancer (the first being Hepatitis B vaccine which prevents liver cancer). HPV vaccine prevents HPV infection, which is responsible for almost all cases of cancer of the cervix in women. In Western countries cancer of the cervix is much less common than in developing countries, because the regular cervical screening (Pap smears) identifies and treats very early cases. HPV is very common in developing countries like Vietnam, and the cancers that it causes are usually detected late, leading to high mortality. HPV is also responsible for a variety of other cancers affecting both men and women, including penile cancer, anal cancer and throat cancer. The vaccine is used is most industrialized countries, and is given to girls, and in some countries to boys as well. It has been introduced into very few developing countries, because of its high price, and the lack of evidence about HPV infection and disease in those countries. Vietnam is a rapidly modernizing country, with a booming economy and a population that is becoming increasingly westernized. HPV is spread by unprotected sex, and rates of infection are very high among sex workers and men who have sex with men. This project will study the rate of HPV infection among young university students in north, south and central Vietnam to get a national perspective. We will also study two important high risk groups, sex workers and men who have sex with men in both the north and south. We will use the records of the cancer hospitals in Vietnam to estimate the proportion of the population who were affected by HPV associated cancer, and to understand better the ages affected and the outcome and treatment costs of cases. This will enable us to predict the effect of HPV vaccine introduction on the community and calculate the money that will be saved by the health system if those cancers are prevented. Finally we will develop, within Vietnam, the laboratory skills that are needed to study HPV disease, and especially to undertake a trial of HPV vaccines in Vietnam. The trial is not covered by this proposal, but we hope in future to do a trial that will help us to decide which is the simplest and therefore least expensive, way to introduce HPV vaccine into a developing country like Vietnam. The project will be undertaken jointly by five institutions. The three Vietnamese institutions (two in the north and one in the south) will be able to share their expertise in this area and also develop new skills with help from expert groups in London (London School of Hygiene and Tropical Medicine) and Australia (Murdoch Childrens Research Institute).


Food Safety & BSE/Ruminant Feed Ban Support Project

The safety of the nation's food supply is critical in the advent of recent pathogenic outbreaks and global food and feed adulteration incidents. Agricultural production systems form the base for a healthy population and a strong economy. This grant will address human and animal safety by evaluating feed products for adulterants and natural toxins that have not been scrutinized in the past with the aim of a safer food supply for the United States.


Purpose and goal:
The aim was to update the image of what an innovator is today and who innovates. The project was announced to the VA´s netwok and readers, and winners were highlighted in a special innovation edition of the magazine.

Expected results and effects:
By Veckans Affärer reaches Vinnova over 300,000 decision makers in business: online, newsletter, magazine and event.

Approach and implementation:
The collaboration at the event was successful and the results were estimated according to the evaluation. All according to contract.


Commercialization and Design of Radio Frequency Coils and Hardware for MRI

No summary - Aucun sommaire

Natural Sciences and Engineering Research Council of Canada


Cell biological mechanisms of centromere drive

Per FOA PA-20-272 this document is not required


Carbon conversion in mixotrophic cultivation by a thermophilic cyanobaterium producing PHB

In the present research, the utilization properties of carbon and energy sources were characterized in the photomixotrophic cultures of a thermophilic cyanobacterium (Synechococcus sp.MA19) and liverwort cells (Marchantia polymorpha HYA-2F), and the following results were obtained.(1) Sucrose was selected as an organic carbon source which was utilized by strain MA19 under a photomixotrophic condition. It was found that phosphate was a key factor governing the productivity of poly-β-hydroxybutyrate (PHB) by the strain.(2) In the cultures of stratn MA19 with sucrose medium in the range of incident light intensity of 0-67 W/m^2, the cellular carbon recovery of 1.1 and CO_2 evolution ratio of -0.18 were obtained when the total light energy absorbed by the cells was 5.8×10^6 J/g-cells. This result inducated that CO_2 released via respiratory actions was trapped and reused for the cell formation by photosynthetic activity of the strain.(3) A bioreactor system was developed for the photomixotrophic cultures of M.polymorpha HYA-2F, which consisted of a glass vessel with external light irradiation and a light moderator installed in a process controller. Batch culture in the bioreactor was conducted in glucose medium while keeping the value of absorbed light energy at 3.5×10^2 W/kg by regulating incident light intensity ranging from 19 to 220 W/m^2. During this culture under light control, CO_2 evolution was suppressed and the high value of cell yield was achieved compared with that in the culture conducted at constant incident light intensity of 50 W/m^2.(4) The characteristics of energy conversion through respiratory and photosynthetic actions in the mixotrophic cells were examined based on the metabolic flux analysis. In the culture with light regulation where the efficiency of overall energy conversion to ATP was considered, the enhanced cell yield was obtained on the basis of energy provided to the system in comparison with those in the cultures without light control.


Community Partnership for Ethical Research

7. PROJECT NARRATIVE This project from Virginia Commonwealth University proposes to address the challenging goal of translating best practices into the community and subsequently improving health outcomes in minority, underserved and vulnerable populations by building research partnerships with these communities. We will work with affected communities to build, monitor, adjust and evaluate a community consultation and public disclosure plan for an emergency medicine research project. We hypothesize that this community based participatory research strategy will result in open communication channels for this project and test a larger, enterprise wide, sustainable, model of community participation in biomedical and social/behavioral research.


異種のフテロ元素の特性を活用したハイブリッド型不斉触媒の開発

本研究は異種のヘテロ元素の特性を活用したハイブリッド型不斉触媒を開発し新しい不斉反応の可能性を開拓するものである。まず、不斉配位子としてイミダゾール誘導体の合成を検討した。従来の触媒的不斉合成法は適用することができなかったので、光学活性な保護基の導入による不斉合成を検討した。光学活性な6-フェニルテトラヒドロピラニル基をイミダゾールの1位に導入後2位のリチオ化と続くアルデヒドへの付加により種々の(1-ヒドロキシアルキル)イミダゾール誘導体を合成した。また、光学分割による合成も行った。一方、ピラゾール誘導体の合成も検討し、軸不斉ピラゾール誘導体が得られた。これらの光学活性なヘテロ環化合物を不斉配位子として種々の反応に用いた。その結果、エノラートの不斉プロトン化でイミダゾール誘導体が60%eeを超える不斉誘起を示した。また、ランタノイド金属イオンを用いる不斉マイケル付加反応では軸不斉ピラゾール誘導体が有用で、50%ee以上の付加体が得られた。最後にサレンマンガン錯体と今回合成したヘテロ環化合物とのハイブリッド型不斉触媒による反応を検討した。サレンマンガン錯体は遊離のオレフィンの不斉エポキシ化の触媒として大変有用であることが筆者らの研究等により既に明らかになっている(有合化,53.940(1995))。この錯体に光学活性な軸配位子を導入すればさらに有用な反応になると期待される。そこで、まず光学活性な軸配位子による不斉誘起能を明らかにする目的で、アキラルなサレンマンガン錯体と種々の光学活性な軸配位子とのハイブリッド化を検討した。その結果、今回合成したイミダゾール誘導体を用いた時に初めて20%eeを超える光学純度のエポシキドが得られることが判明した。高くはないが不斉誘起が観測されたことは、反応機構などを考察するうえで大変重要である。また、不斉触媒反応における新しい方法論を提供するものとして実用上も有用であると考えている。


Food Allergy Research Consortium and Statistical Center


Innate immune response to microbial infection


Gokova Geometry-Topology Conference will be held during the last week of May of each year in Hotel Yucelen's conference facilities in Gokova/Turkey. The annual international Gokova Geometry-Topology Conferences was founded in 1992 with the purpose of creating a lively informal environment where the latest results of Geometry and Topology are discussed by active world-renowned experts and junior researchers along with enthusiastic graduate students. Many junior now-well-known mathematicians of the field got their early international exposure in these friendly conferences. These conferences aim to increase participation of junior researchers and experts from US. Gokova conferences will continue to provide a platform for exchanging ideas between American, European and Asian mathematicians in timely fashion.

The focus topics for each conference are  determined by the Scientific Committee during the previous year based on the major scientific breakthroughs that occur in the field, and on  availability of outstanding speakers to present them to a broad audience of geometers and topologists. The list of the topics of current interest that the organizers hope to explore via mini-courses and/or lecture series in the next few years include: C. Manolescu's solution of the triangulation conjecture (Manolescu will be giving a minicourse in 2015 meeting); Flexibility phenomena in symplectic and contact topology (Y. Eliashberg, E. Murphy, and collaborators,one of them will be  minicourse); Geometric approaches to mirror symmetry and extensions of the Strominger-Yau-Zaslow conjecture (D. Auroux, K. Fukaya, M. Abouzaid, T. Ekholm); Corks, surgeries, and exotic 4-manifolds (Akbulut, Yasui, Ruberman); Refined enumerations and knot theory (Cherednik, Goettsche, Shende). More information can be found on the conference web page.
 http://gokovagt.org/


酵素類似機能を有する有機金属錯体の合成とN_2, CO_2固定に関する研究

Principal Investigator：御園生 晃, Project Period (FY)：1968, Research Category：Grant-in-Aid for General Scientific Research (B)


Chaire de recherche du Canada en études allemandes et européennes /

Canada Research Chair in German and European Studies

Social Sciences and Humanities Research Council of Canada


Studies in cochlear hair cell transduction

Of the well over 30 million people in the US with auditory problems, the vast majority have defects in outer hair cell (OHC) function. These sensory receptor cells within the cochlea are required for normal sensitivity and frequency selectivity. Because their loss or malfunction results in major processing difficulties, our work on both normal and genetically altered OHCs is required in order to improve clinical outcomes.


兼任取締役の忠実義務に関する研究

Principal Investigator：北村 雅史, Project Period (FY)：1992, Research Category：Grant-in-Aid for Encouragement of Young Scientists (A), Research Field：Civil law


Processes of litter and soil organic matter transformation during extreme drying/wetting as assessed by compoundspecific isotope approaches

Recently, intensive droughts followed by heavy rainfall can already be observed in Europe as proposed by climate models. Shifts in amount, intensity and frequency of precipitation could change soil structure and soil organic matter quality and thus turnover in temperate forest ecosystems. Contradicting results have been reported from drying and wetting experiments in field and laboratory studies or from observations of natural drying and wetting periods. To verify different interpretations, a combination of stable and radio-isotopes and biomarker .analyses seems a promising tool. This can be achieved by establishing tracer experiments in the drying and wetting fields (13C and 15NJ and in controlled laboratory studies (14C, 13C, and 15N) and by analysing the 13C, 14C and 15N signatures not only in the bulk SOM but also in biomarkers characterizing chemically defined SOM pools, e.g. microbially and plant-derived sugars, phospholipid fatty acids (PLFA) and benzenepolycarboxylic acids (BPCA). The combination of biomarker and isotope (δ13C, 14C and δ 15N) analysis allows not only deducing SOM turnover after drying / wetting but also to identify the involved microbial community and the fate of chemically defined compounds during SOM decomposition and turnover under the experimental manipulations.


琉球石灰岩地域の地下水・湧水, 河川水の汚染に関する研究

Principal Investigator：渡久山 章, Project Period (FY)：1984, Research Category：Grant-in-Aid for Environmental Science


PROPOSAL NUMBER: CNS-0448246
PRINCIPAL INVESTIGATOR: Gupta, Indranil
INSTITUTION: University of Illinois at Urbana-Champaign
PROPOSAL TITLE: CAREER: Systematic Design of Distributed Protocols
- from Methodologies and Toolkits to Systems

Distributed protocols such as resource discovery, cooperative caching, replication, etc., are crucial to the scalability and reliability of large-scale distributed systems such as the Web and the Grid. Today, however, the critical activity of designing a distributed protocol relies on an ad-hoc approach - literature, experience, and basic Computer Science knowledge provide the only assistance. This often leads to complex protocols, increased design times and costs, and eventually to inefficient use of research potential.

This project is exploring systematic techniques for designing distributed protocols, assisted by the use of Design Methodologies for distributed protocols. Design methodologies augment the creative process of protocol innovation, without stifling it. The project is creating new methodologies that systematically convert naturally observed phenomena into protocols with predictable properties. One innovative methodology translates differential equation systems into equivalent distributed protocols. Composable methodologies are also being developed, allowing protocol designers flexibility to enrich protocols with desired properties.

The methodologies invented and discovered in this project will be used to design new system designs for cooperative web caching, adaptive Grid computing, persistent distributed file systems, and disaster response and recovery. The methodologies will be made available to the community as Integrated design Toolkits (IdTs) that automate methodologies and enable a designer to automatically generate compilable code for a protocol. While methodologies have been used with varying degrees of success in other fields of science, this project is the one of the first to study its benefits and drawbacks in certain focus areas of distributed systems.


Partnering with stakeholders to set research priorities in pediatric obesity management

Our purpose is to create a 'Top 10' list of research priorities for managing pediatric obesity in Canada. To achieve this goal, we will survey adolescents (n=270), caregivers (n=270), and healthcare professionals (n=100; doctors, nurses, dietitians, mental health professionals) about the questions they have related to managing pediatric obesity. We will recruit families and healthcare professionals through Obesity Canada and from pediatric obesity management clinics in Vancouver, Calgary, Edmonton, Thunder Bay, Mississauga, Toronto, Hamilton, Ottawa, and Montreal. From January to December 2023, we will complete a multi-step process called a Priority Setting Partnership, which includes (1) collecting numerous research questions from participants (in English and French), (2) organizing and refining questions, and (3) creating a 'Top 10' list of research priorities. Our team has a long, successful history of conducting research together. This study will generate a list of questions that we will use to plan future research related to managing pediatric obesity. The information we learn from this study will ensure that our future research addresses topics that are most important to families and healthcare professionals.

Planning and Dissemination Grant - Institute Community Support


BIFUNCTIONAL CHELATING AGENTS IN TUMOR LOCALIZATION


BIOLOGY OF ONCOGENES AND TUMOR SUPPRESSOR GENES


Responsivity Biomarkers of Maximum Oxygen Consumption in Aerobic Training: A Metabolomics Approach

Maximal Oxygen Consumption (VO2MAX) is the gold standard measurement of cardiorespiratory fitness levels, and is positively associated with maintenance and health enhancement. Even though the recommendations for aerobic levels enhancements can promote benefits for the great majority of people, the responses may vary from individual to individual, who will be classified as either high or low responders. The understanding of factors related to aerobic training responsivity, as well as identification of specific biomarkers that can assist in individual response capacity diagnosis, may contribute to an adoption of more efficient and biologically individualized training strategies. Thus, the current study will investigate metabolic biomarkers in skeletal muscles and blood samples related to the responsivity of 68 healthy young men (18-30 years old) to VO2MAX. Subjects will undergo 8 weeks of continuous aerobic training (TAC - 40 min/day, 3-4 times/week with 70% heart rate reserve, n=34) and high intensity interval training (HIIT - 40 min/day, 3-4 times/week with 50-90% heart rate reserve, n=34) using a cycle ergometer. Blood samples and muscle tissue (vastus lateralis) will be collected pre and post training protocol. All samples will be analyzed through metabolomics method (1H NMR spectroscopy). The main goal is identifying metabolites that can be predictors of enhancement in VO2MAX due to individual responses. After the training protocol, based on the changing magnitude of VO2MAX the individuals will be classified as either ""high"" or ""low"" responders after. Finally, metabolites identification will be used to explain differences in VO2MAX of ""high"" and ""low"" responders after TAC and HIIT program. Identification will be found through correlations and multivariate statistical analysis such as principal components analysis (PCA), partial least squares discriminant analysis (PLS-DA) and linear regressions. Receiver operating characteristic curve (ROC) will be utilized to characterize metabolites and biomarkers, their accuracy will be assessed through sensibility and specificity tests. (AU)

Fundação de Amparo à Pesquisa do Estado de São Paulo

Universidade Estadual de Campinas (UNICAMP). Faculdade de Educação Física (FEF)


血管新生部の血管内皮細胞と周細胞との細胞質突起相互陥入の三次元電顕免疫学的研究

Principal Investigator：和久井 信, Project Period (FY)：1991, Research Category：Grant-in-Aid for Encouragement of Young Scientists (A), Research Field：基礎獣医学

Japan Society for the Promotion of Science


Biomedical Informatics Research Training at Oregon Health & Science University

Project Narrative The Oregon Health & Science University (OHSU) Biomedical Informatics Fellowship Program trains future researchers and leaders in biomedical and health informatics, the field devoted to improving personal health, health care, public health, and biomedical research through the use of information and its associated technologies. This National Library of Medicine (NLM) Training Grant will enable us to support predoctoral (PhD students) and postdoctoral fellows for training that includes courses, research, and related activities. This proposal is a competitive renewal for a fifth five-year cycle of funding for the OHSU program, which has been a leader and innovator in the program for 20 years.


SBIR Phase I:  Improved Photoionization Source for LC/MS Analysis for Food Safety

This Small Business Innovation Research (SBIR) Phase I project will lead to a new technology for analyzing contaminants in food substances. This is an extremely challenging analytical problem due to the vast range of contaminants that need to be screened and the complex and varied matrices of different food commodities. The state-of-the-art in analysis is based on electrospray ionization (ESI) and liquid chromatography mass spectrometry (LC-MS). Unfortunately for environmental and biological samples ESI suffers several limitations including matrix ion suppression, poor dynamic range, and inability to ionize nonpolar compounds. We will significantly improve on the analytical accuracy of food contaminants by implementing atmospheric pressure photoionization (APPI), which allows much better control of the undesirable ion-molecule chemistry that plagues ESI. We will test combined ESI/APPI configurations and modes of operation and achieve critical control of ion-molecule interactions from dual ionization. A total system approach will be investigated to develop the optimum technology solution.

The broader/commercial impacts of this research are: (i) significantly improved analysis of harmful compounds in foods providing significant societal benefit in terms of health, well being, and lower healthcare costs, (ii) significant new revenue to Syagen through increased sales off APPI-based products, (iii) improve the technical competitiveness of the U.S. in food safety for which Europe currently leads, and (iv) increase the value proposition for expensive analytical instrumentation by improving the quality and speed of chemical analyses.


Preterm Infants: Light Effects on Health and Development


RESEARCH FOR THE PATHOMECHANISM, EPIDEMILOGY AND TREATMENTS FOR HAM AND HTLV-I RELATED DISORDERS.

This research provided several important results during these two years of investigation. In Kasari-town, which is a remote island in Kagoshima, we examined 384 inhabitants. Among them, 36(9.4%) had anti-HTLV-I antibodies in the serum. A longitudinal study of carriers will be done in the coming ten years. Lymphocyte separation was performed from 800 patients and family members who were admitted at Kagoshima University hospital. All of these samples were stored in liquid nitrogen.The clinical features and the laboratory data of 208 patients with HAM were entered in the computer for analysis. The results provided several important information regarding HAM. For instance, HAM may not sometimes have anti-HTLV-I antibodies in cerebrospinal fluid. The associated diseases in patients with HAM were also analyzed and their prevalence were calculated. The pathomechanisms of HTLV-I associated arthropathy, alveolitis, Shjogren syndrome, myositis. IgA nephropathy and pseudohypoparathyroidism were investigated and several important findings could be obtained. Five autopsied cases HAM were studied for neuropathological analysis. The specific importance of CD8lymphocytes was observed. Cytotoxic CD8 cells for the pX region were also found in the blood of patients. More than ten different therapeutic regimens were tried in HAM with very encouraging results.


EPSTEIN-BARR VIRUS AND AUTOIMMUNE DISEASE


MicroRNAs in Tissue-resident memory T cells

Narrative A defining feature of the immune system is the existence of memory cells, which originate in response to an infection, and provide durable immunity during subsequent infections; tissue-resident memory (TRM) cells are one class of memory cells, and reside in each adult tissue and provide localized response to infection. Here, we propose to systematically examine whether microRNAs, a class of gene regulatory RNAs, contribute to TRM cell regulatory programs, using human and mouse cells. This study is a pivotal first step towards understanding how specific miRNAs can be used to promote more durable immunity by increasing the formation and survival of TRM cells.


CAREER : Filling In the Design Landscape of Probabilistic Programming Languages

Probabilistic behavior is pervasive in computing, so it is critical that we have tools for reasoning about it in our programs. Probabilistic programming languages (PPLs) address this need by enriching programming languages with probabilistic semantics, enabling applications in software verification and artificial intelligence that rely on reasoning about the uncertain behavior. The challenge is scalability: probabilistic inference is computationally hard, even for very restricted programming languages. However, scaling inference is not hopeless: its inherent hardness can be tamed by careful language design. There are special PPLs, called tractable probabilistic models, for which inference is computationally easy. Unfortunately, tractable probabilistic models are too low-level to ergonomically program in. The goal of this project is to bridge the gap between high-level ergonomic languages and low-level tractable languages. This project's novelty is a new compiler-oriented approach to designing and implementing PPLs: the team will (1) develop new high-level ergonomic PPLs that compile to low-level tractable probabilistic models; (2) develop new compilation targets that enable scalable probabilistic inference for richer classes of programs; and (3) create new PPLs for teaching probability to broad audiences. This project's impact is a new generation of scalable, reliable, and usable PPLs, enabling new applications in software verification and artificial intelligence.

To achieve these goals, the project will fill in the design landscape for probabilistic programming language design and implementation. The key tradeoff in designing a PPL is between tractability and expressivity of the language. More tractable languages afford efficient and scalable inference strategies but are not easy to program in. More expressive languages have ergonomic programming features like loops, data structures, and modules, but these features make performing inference hard. The project's first research thrust will develop and grow a new expressive compiled PPL that supports a significant subset of the Racket programming language. The project's second thrust will use type systems to develop new tractable probabilistic programming languages that ensure high-performance Markov-Chain Monte-Carlo sampling with guarantees on mixing times. The project's final thrust will develop a sequence of increasingly rich PPLs for teaching probability to broad audiences. The project's education plan will enable (1) a new pedagogy for teaching probability using probabilistic programs; and (2) new courses on probabilistic programming. The project's broader impacts are (1) development of new educational tools for teaching probability to broad audiences; (2) technology transfer of probabilistic programming tools and techniques into industry and government; and (3) empowering a broader set of developers to create machine learning models.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.


Network-based Analysis of Kinetics and Regulation


THE EPIDEMIOLOGY OF EARLY REPRODUCTIVE LOSS


Presidential Award for Excellence in Secondary Mathematics  (PA)


Rhenium-Osmium Isotope Study of the Mantle

9526329  Walker  Despite its importance in understanding the chemical evolution of the Earth, the Os isotopic composition of the mantle is poorly constrained.  This is to continue characterization of the Os isotopic composition of various mantle domains through time, via the analysis of ultramafic rocks that are otherwise geochemically and isotopically well-characterized, and that have relatively high Os concentrations and low Re/Os ratios.  Specific targets for analysis will be ultramafic magmatic systems that represent upper oceanic lithospheric materials, and materials derived from likely mantle plumes.  Both whole rock samples and mineral separates will be analyzed from each location.  The resulting information should lead to:  1) a better understanding of how Os has evolved in plume and upper mantle reservoirs, and 2) provide insights into where Re and Os are sited in these types of rocks and what phases or combination of phases provide the most useful information about initial isotopic compositions.


Coordinated Regulation of Virulence Genes in C. neoformans

In order to better treat infectious diseases, we must understand the ways in which infectious microorganisms survive within their host. The experiments in this proposal will study Cryptococcus neoformans, an important opportunistic fungal pathogen in AIDS patients, to define the cellular factors required for formation of a protective surface capsule. Capsule production will also be used as a model to better understand more fundamental issues of the interaction between microorganisms and the infected host.


INSERTIONAL MUTANTS AND DEVELOPMENT IN TRANSGENIC MICE


MODULATION OF GLOMERULAR ULTRAFILTRATION COEFFICIENT


UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON


ヘムタンパク質及び金属ポルフィリンの機能及び構造とそれらの分子制御に関する研究

Principal Investigator：城 宣嗣, Project Period (FY)：1986, Research Category：Grant-in-Aid for Encouragement of Young Scientists (A), Research Field：工業物理化学


Factors affecting compensation decisions of Canadian firms, and the impact of compensation schemes on managerial decision-making

Social Sciences and Humanities Research Council of Canada