Fatty liver versus autoimmunity of the bile ducts - defining the gut signals driving steatosis and inflammatory disease of the gut-liver axis

The obesity epidemic has caused a surge of metabolic-dysfunction associated steatotic liver disease (MASLD), an important cause of morbidity and mortality. This also leads to other liver diseases presenting with steatotic (fatty) liver as a “second hit”, with unpredictable impact on clinical outcome. In the present project, I will use the co-existence of two different liver diseases to study how the gut microbiome interacts with steatosis and autoimmunity. Both MASLD and primary sclerosing cholangitis (PSC), an autoimmune disease of the bile ducts, are more common in inflammatory bowel disease (IBD) than in the population, suggesting they are driven by gut microbial activity (gut signals). However, MASLD and PSC co-exist less frequently than expected, appearing to protect against each other. Separate gut signals could therefore influence these conditions, and a driver of one disease could even protect against the other.  Studies of PSC-MASLD-IBD provide a unique window to define how gut signals interact to cause and drive liver health, which would be of great importance in MASLD and PSC, where few effective therapies are available.I have in the ongoing ERC Starting Grant StopAutoimmunity shown that PSC is associated with large changes in microbial functions, motivating the novel hypothesis that distinct gut-derived signals drive autoimmunity of the bile ducts and steatotic liver disease. I will use an extensive set of methods established in my group to define the gut signals acting in PSC and MASLD and liver health. I have available unique cohorts and materials from these conditions, and experimental models based on human microbiome. The expected outcomes include the first detailed description of this clinical problem and the identification of distinct gut signals driving and protecting against steatosis and biliary autoimmunity, serving as basis for diagnostic and prognostic tools, and new targets relevant for trials to prevent and treat liver disease.

HORIZON EUROPE European Research Council


The proposed workshop will bring together scientists and                        database researchers to identify the requirements and design                    criteria appropriate for scientific database software.  In                      particular, the workshop participants will seek to identify the                 problems which can be solved by existing database software and,                 more importantly, determine those problems which are not being                  addressed by existing database software and for which solutions                 needs to be developed.  The goal will be to produce a planning                  document to help guide research toward producing viable                         scientific database management systems.


Cars for field work and equipment repairs.

Cars for fieldwork and repair of equipments:The itens requested include two Pick-up for fieldwork and funds for maintenance of the da meteorological Tower of IAG.Two Pick-up are needed for fieldwork in Applied Geophysics, in their studies of exploration of mineral resources. Some examples are: silting of rivers and lakes in the Pantanal basin at  Mato Grosso (Coxim-MT); studies of arqueologicalsubaquatic sites at the  baixada Maranhense(Santa Helena-MA); geophysical investigations of the exploration of natural resources such as barite ore (Tunas do Paraná-PR); exploration of industrial sand (Leme-SP) and exploration of marmore(Campos de Jordão-SP), hydrogeological studies at Extrema-MG and at Guarapuava-PR, among others.The item  maintenance of meteorological Tower of IAG refers to the fact that in the last 20 years the measurements are carried out with automatic stations, with no interruption, at the Parque Cientec.Differently from the conventional instruments, the sensors of the automatic stations require maintenance, calibration and more frequent exchange of pieces. The dismounting and remounting aimsat moving the Tower to the new place where there will be only the automatic instruments and sensors. (AU)

Fundação de Amparo à Pesquisa do Estado de São Paulo

Auxílio à Pesquisa - Reserva Técnica para Infraestrutura Institucional de Pesquisa

Universidade de São Paulo (USP). Instituto de Astronomia, Geofísica e Ciências Atmosféricas (IAG)


Paleomagnetism of the Avalonian Margin of Iapetus

The northern Appalachians contain a number of exotic terranes, accreted during  the closure of the Iapetus ocean that involved elements of North America and Laurentia as well as  Gondwana.  However, the timing, geometry and terrane positions are still incompletely known.  This  project will focus on the western margin of Avalon, one of the more important terranes, in Maine, and  the Maritime provinces of eastern Canada and will involve paleomagnetic, geochronologic and tectonic  investigations.  Results will be useful in testing the large number of contrasting tectonic scenarios  that have been proposed for the Appalachian Caledonian belt, in particular the tectonic setting and  locations of major arc/back arc systems in the southern portion of Iapetus.

Regents of the University of Michigan - Ann Arbor


Determining the roles(s) of HIV-1 Nef in enhancement of virion infectivity


生理活性ペプチドによる冠血管調節機構

Principal Investigator：斎藤 亜紀良, Project Period (FY)：1988, Research Category：Grant-in-Aid for Encouragement of Young Scientists (A), Research Field：General pharmacology

Japan Society for the Promotion of Science


REVISION OF THE WORLD HEALTH ORGANIZATION MANUALS


Habermasian Bioethics: a new approach to emerging biomedical technologies?

The objectives are as follows: 1. To bring together a group of scholars working in bioethics to explore the theoretical coherence of the Habermasian approach. 2. To produce a body of work that is potentially publishable on the topic. 3. To set agendas based on the need for further investigation of developing themes and issues. 4. To plan for further seminars.


Managing medium density development: a municipal case study

There has been no applied, local government-focused research on medium-density residential development. This issue creates the most political and planning problems for many urban local governments in Australia. Using the case study municipality of Boroondara (Melbourne), the aim is to identify, explain and address the many problems associated with such development. This will advance our knowledge about the implications of medium density housing for municipalities and thus enable the implementation of better management practices.


Neural control of respiration in lampreys

Respiration is a vital motor behaviour that begins at birth and is maintained throughout life. Pathological changes in breathing can have dire consequences and it is thus crucial to understand the neural mechanisms generating respiration.  To do this, both the synaptic connectivity of the entire network as well as the membrane properties of the comprising generator neurons must be identified. The complexity of the mammalian Central Nervous System (CNS) has rendered this task difficult and we believe that the simpler CNS of lampreys could help provide a detailed understanding. In lampreys, the neural circuitry generating respiration stays active for two days after isolation in vitro of their CNS, and continues to generate respiratory output very similar to that observed in intact animals. We propose to examine the neural circuitry both at the system (synaptic connectivity) and cellular (intrinsic properties of neurons) levels in the CNS of lampreys.  The relative contribution of synaptic and intrinsic properties in respiration will also be examined.  Finally, we will examine the modulation of respiration by other motor circuits in the isolated CNS.  The onset of movements is accompanied by increases in the respiratory drive and previous work from our lab has revealed that the changes are pre-programmed in the CNS.  We propose to identify the neural circuitry responsible for these changes. We believe that the information gained in this lower vertebrate CNS will be useful to provide testable hypotheses on the neural organization responsible for respiration in higher vertebrates, including humans.

Natural Sciences and Engineering Research Council of Canada

Research Tools and Instruments - Category 1 (<$150,000)


CAM Use in Hispanics 75+ Years Old in US &Mexico

UNIVERSITY OF TEXAS MEDICAL BR GALVESTON


Effects of Common Polymorphisms in Immune Sensors in Tumor Immunosurveillance

PUBLIC HEALTH RELEVANCE: At least 30% of individuals in the general population are carriers of a limited set of polymorphisms in pattern recognition receptors (PRRs) genes. Although these polymorphisms are compatible with a healthy life, they are functionally relevant because the carriers' susceptibility to develop certain infectious and/or autoimmune diseases is altered. Still, how mechanisms of tumor immunosurveillance are affected in these individuals remains completely unknown. The proposed studies will exert a profound impact in the field by elucidating how 7- 10% of individuals in the general population carrying a polymorphism that inactivates TLR5 function in a dominant negative fashion respond differently to primordial mutagenic events, orchestrate superior anti-tumor immunity and, correspondingly, exhibit better prognosis. Besides providing a mechanistic rationale to establish novel prognostic models, results derived from the proposed Aims will also contribute to understand whether these carriers may be more responsive to immunotherapeutic interventions, thus providing a significant advance towards the goal of personalized Medicine.


AIDS Malignancies Training and Research International Program (AMTRIP)

PUBLIC HEALTH RELEVANCE: While AIDS-associated cancers are a major cause of death around the globe, those in low- and middle-income countries (LMICs), particularly in sub-Saharan Africa, are much more likely to die from cancer due to shortages of trained cancer researchers, oncologists, and support staff and a lack of healthcare infrastructure and expertise for diagnosing and treating cancers. The proposed program will train a cadre of Zambian biomedical researchers and practitioners from the Cancer Diseases Hospital (the main LMIC institution) and partnering organizations in the skills necessary to further the country's research agenda in cancer biology and genomics. Upon completion of master's and doctoral training, program fellows will be provided employment in Zambian medical institutions in order to begin addressing these challenges in-country.


Advances in Design of Automated Wire and Die Bonding        Machinery in Microelectronic Manufacturing

This research addresses two discrete problems that have                    arisen in the automated machinery that performs the die and wire                bonding operations in microelectronic manufacturing with very                   high throughput.  The problems in machine design are a result of                inadequate fundamental understanding of problems in heat transfer               and metal to metal and metal to semiconductor bonding partly due                to diffusion at the material interface.  The research considers                 each of these problems and addresses the solution through a                     combined experimental program with physical/numerical modeling.                 Laboratory facilities are available for the experimental research               and access to large scale computers is available for the                        numerical modeling.


Development of a novel mouse model of mosaic mutation-induced diseases caused by somatic mutations

皮膚病では体細胞突然変異が原因となり生じるモザイク変異疾患が数多く見られる。汗孔角化症の皮疹は直径数mm程度の大きさで皮膚に多発するが、皮疹のゲノムのみに後天的な遺伝子変異（セカンドヒット）が生じると考えられている。疾患モデルマウスを作製し発症機構を調べるためには、表皮細胞の一部だけに遺伝子ノックアウトまたは変異を導入し、かつその細胞を蛍光標識して解析する必要がある。本研究では、頻度は稀であるが一個の細胞内では確実にCre反応が起きるシステム及び皮膚疾患において高頻度で起きていることが明らかになったLOH(loss of heterozygosity）検出マウスの作製のための技術開発を行う。

Grant-in-Aid for Scientific Research (C)


ECHOCARDIOGRAPHY OF REGIONAL MYOCARDIAL PERFUSION


Untersuchung von Hypothesen zur magnetischen Orientierung von ziehenden Fledermäusen unter Laborbedingungen und im freien Flug

Für das ganzheitliche Verständnis der Magnetrezeption und Navigation der Vertebraten, ist es essentiell zu verstehen, ob die Mechanismen und Prinzipien der Magnetwahrnehmung auf diverse Artengruppen übertragbar sind. In diesem Projekt werden wandernde Fledermäuse studiert. Wir erfassen das Orientierungsverhalten der Tiere unter Einfluss von Magnetfeldmanipulationen einerseits in einem kontrollierbaren Feldlaboratorium, und andererseits mithilfe automatisierter Radiotelemetrie-Stationen im freien Flug, unter natürlichen Umweltbedingungen, um so die Hypothesen zum Radikalpaar- und den auf Magnetpartikeln basierenden Mechanismus zu testen.

Carl von Ossietzky Universität Oldenburg


The role of diet, as mediated by the gut microbiome, on childhood arthritis disease activity: a feasibility intervention study.

Families of children with arthritis are highly interested in the benefits of diet to improve their child's disease state and future health outcomes. We know from previous research that the germs - bacteria and other organisms - that live in our intestines (gut microbiome) are important to how well our immune systems work, and we know that what we eat changes our gut microbiome. We want to study whether a certain diet - the Mediterranean Diet - will improve the microbiome and will, in turn, improve arthritis for children. Thirty-six participants in this study will change their diet for an 8-week period, and will have the option of remaining on the diet for an additional 4 weeks. Participants will have 4 study visits. The first visit will be a study orientation visit. During the other visits, participants will provide stool and blood samples, will complete questionnaires about diet and other aspects of lifestyle and health, and will complete a disease assessment by a clinician. We will determine whether we can collect all of these samples and information; then we will be able to plan a study to determine if the followed diet was successful in improving disease activity in children with arthritis and if the way of doing so was through changing the bacteria and other organisms that live in our intestines. This research will indicate whether it is possible to do this type of study in a much larger population across Canada and the United States, which would provide important scientific confirmation of the effect of diet on disease activity in childhood arthritis. If successful, this research will provide scientific knowledge to help families make their way through this difficult-to-navigate topic.


構造指向剤の複合化による新規構造ゼオライトの開発

安価で比較的容易に入手可能な有機化合物,あるいは単純な構造の有機化合物を構造指向剤(SDA)として用いることにより,新規構造を持つゼオライト物質の探索を行った。計画最終年度である本年度は,引き続き新規構造物質の探索研究を行いながら,合成の対象を拡張し,安価で環境負荷の低い合成法を開発した。前年度に引き続き,ヒドロキシル基を持つ四級アンモニウムカチオンをSDAとして用いゼオライトを合成した。様々なヒドロキシル基含有SDAから新規構造を持つ層状シリケート物質が得られ,それらを焼成することによりゼオライト物質が得られた。層状シリケートの合成に最適な合成条件(母ゲル中のケイ酸濃度やpH,合成温度など)は,通常のゼオライト合成で用いられる条件とは異なるため,これまでに行われていない領域での合成が可能となった。最終的に得られたゼオライト物質は既知構造物質であったが,この層状シリケートを経由するアプローチが新規ゼオライト合成に対して有効である可能性が示唆された。次に,同様の単純な構造のSDAを用いながら,工業触媒としても用いられているチタノシリケートへと合成対象を拡張した。この合成法では,チタニアのような安価な原料を粉砕、混合して調製した複合粉に単純な構造のSDAを加え,水蒸気中で熱処理することによりチタノシリケートを結晶化させた。この合成法の開発により,安価な原材料が利用可能なだけでなく,廃液や副生成物の生成無しにチタノシリケートを得ることが可能となった。なお,これまでの研究成果としていくつかの未知構造物質が得られているが,計画年度内にこれらの結晶構造を解明するまでには至らなかった。ゼオライトの構造解析は一般に困難であるが,得られた生成物の結晶性が低いこともこの原因となっている。これらの未知構造物質については,引き続き合成条件の検討と最適化を行いながら,結晶構造の解明に努めたい。

The University of Kitakyushu(2007)Tohoku University(2005-2006)


SBIR Phase I:  Low-Power, Wireless Crop Quality Sensors for Grain Quality Preservation and Storage Automation

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to increase the returns of grain storage for farmers and reduce overall postharvest loss due to toxin and insect damage.  Ten billion bushels, over half of US grains, are stored on-farm each year for 3-12 months.  During this period, grain is susceptible to spoilage, infestation, and moisture loss?all of which impacts the price a farmer receives at the time of market delivery.  There is no easy way to monitor grain quality changes throughout the storage season to optimize for best times to run aeration controls to preserve, condition or maintain the grain.  This leaves farmers with a ?gut check? system of driving to each grain bin site and climbing up and inside units.  Since grain is priced based on moisture baselines, farmers are essentially selling water and weight, their final price outcome can vary significantly based on how well they managed grain conditions throughout the storage period.  In the US, an annual $3 to $ 5 billion dollars (3 ? 5%) of crop value is lost due to toxin, insect and moisture mismanagement that could be prevented through the introduction of affordable and accessible monitoring technology.

The proposed project would advance internet of things automation and wireless sensor applications as applied to production agriculture and the postharvest supply chain.  There are certain, manual processes of farm production that are strenuous due to time burdens and the lack of obtainable information to make decisions.  Monitoring grain assets, the product of farmers? toil and the safety net of global food supply, in farm bins, commercial storage, and barges is one such process. Sensing for when loss and spoilage risks occur, but more importantly connecting and turning the data into automation opportunities before they exist is the aim of this proposal.  Cable-based monitoring solutions exist, but adoption is restricted due to physical installation limitations, electricity/power constraints, and investment costs.  This project will validate the feasibility of a low-power, wireless sensor that can detect grain conditions and last a full postharvest cycle (18 months).  Such a device will create opportunities to track grain qualities across the agriculture value chain, beginning with its use to monitor and automate farm grain storage.  By characterizing, and testing against cable systems and within grain science 3D models, this project will prove the wireless sensor?s direct functionality within this first farm application.

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.

Iowa State Research and Demonstration Farms


Theoretical and Experimental Studies of Particle and Energy  Transport in a Low-Voltage Cesium Discharge


植物プランクトンの産生する特異な遊離脂肪酸の生理活性に関する研究

Principal Investigator：村上 昌弘, Project Period (FY)：1987, Research Category：Grant-in-Aid for Encouragement of Young Scientists (A), Research Field：Fisheries chemistry


Chronic Renal Insufficiency Cohort (CRIC) Study

PUBLIC HEALTH RELEVANCE: This project will study nearly 4,000 patients to better understand the factors and pathways leading to end stage kidney failure, cardiovascular disease and premature death in individuals with diminished kidney function. Understanding the mechanism of progression of chronic kidney disease and its relationship to cardiovascular disease will advance the Objective 4-1 of Health People 2010 to improve the renal health of Americans.


HAN Digital Library of Electronic Resources and Services


EFFECTIVENESS OF UNDERGROUND CONSTRUCTION


MINORITY HIGH SCHOOL STUDENT RESEARCH APPRENTICE PROGRAM


The GEne Therapy INnovation Training Network

Gene therapy has transitioned from a distant hope to reality. To date 3 rAAV gene therapies are approved in the EU, >30 phase III clinical trials ongoing, and exciting developments in therapeutic gene editing in the pipeline. However, fundamental limitations in the bioprocessing of gene therapy vectors limit broader application. Manufacturing is not automated, with an open process environment, limited scalability and robustness, and inefficient downstream processing, resulting in huge footprint and exceedingly high cost of goods. The field requires scalable manufacturing technology with modular design to produce high doses for large patient groups at a fraction of cost. Improved delivery approaches with increased specificity and efficacy at lower doses are needed to overcome emerging safety concerns observed in clinical trials. Prediction of therapeutic efficacy in man is challenging due to a species barrier, underlining the need for humanized models to reduce attrition rates in the development pipeline.

To overcome these challenges, innovation driven by multidisciplinary approaches is direly needed. GET-IN is a doctoral network of 7 academic and 8 non-academic partners, with expertise in vectorology, genome editing, process engineering, biomanufacturing and innovative humanized models. Together, they provide an excellent training framework for 10 Doctoral Candidates (DCs) who will be the future innovators in the gene therapy field. Research in GET-IN will investigate disruptive innovations including optimised bioprocessing, digital simulation, novel and improved vectors and genome editors, targeted delivery systems, and human organ-on-chip models for more relevant safety and efficacy evaluation. The joint training programme will emphasise responsible, cooperative research and innovation, creativity, and entrepreneurship to maximize the career potential of the DCs.


窒素空孔中心ダイヤモンドを用いたメタマテリアルのナノスケール磁場計測と特性評価

Principal Investigator：田中 拓男, Project Period (FY)：2016-04-22 – 2018-03-31, Research Category：Grant-in-Aid for JSPS Fellows, Section：外国, Research Field：Optical engineering, Photon science

Japan Society for the Promotion of Science

Institute of Physical and Chemical Research


Stress Concentrations in Composite  Materials


STUDIES IN LOW ENERGY NUCLEAR SCIENCE


Responsible governance of gene editing of animals: Situating and expanding debates in a Canadian context

Social Sciences and Humanities Research Council of Canada


３次元子宮内膜組織を用いた新規受精卵着床モデルの構築と新規治療法の開発

妊娠成立には受精卵が子宮内膜へ着床し維持されることが重要であるがそのメカニズムは未だに謎が多い。この子宮内膜と受精卵の関係を観察した研究はほとんどなく、より生体に近い状態での観察研究が望まれている。我々が用いている細胞シート工学は、本来ばらばらでしか存在できない細胞をシートの状態で取り扱うことが出来る再生医療技術である。回収した子宮内膜細胞シートを積層化し3次元の子宮内膜組織の作成することで、受精卵との関係を観察することが可能である。この技術を用いることによって、さらなる妊娠率向上に向けた新規診断法や治療法の発見・開発の基礎となることが期待できる。

Grant-in-Aid for Early-Career Scientists


Analysis of spatio-temporarl mechanisms on outer plexiform layer in retina by the multichannel microprobe electrodes array chip

We have developed multichannel microprobe electrode array chips for recording neural responses to light from retina, and mathematical model of retinal neurons to analyze retinal mechanisms involved in the recorded light-induced responses.Prototypes of the microprobe electrode array(MEA) chip have been fabricated on Si(111) substrates by selective Vapor-Liquid-Solid(VLS) growth method. The prototype MEA could detect light responses whose characteristics to a white flash and sensitivities to monochromatic stimulus were consistent with photopic electoretinogram(ERG). We also demonstrated that the changes of localized ERG responses were obtained with stimulus of slit light by the MEA.In order to analyze inner retinal mechanisms involved in the measured ERG responses, we have developed models of retinal neuron and the retinal neural circuit by physiological engineering technique. The models of horizontal cell and bipolar cells which is closely related to form b-wave in ERG responses were described mathematically by their ionic mechanisms. It is allow us to analyze the relationship between light responses and the ionic mechanisms in their neuron.These results suggest that the developed MEA chip is applicable to retinal neural recordings as a new measurement tool, and the models of retinal neuron would play a role to understand visual information preprocessing of retina.

Grant-in-Aid for Scientific Research (B)


LUPUS COHORT-THROMBOTIC EVENTS &CORONARY ARTERY DISEASE


Novel Direct Approaches Toward Bioactive Heterocycles

The synthetic part of the proposed work will be focused on the synthesis of diversely substituted indolizines not easily available by existing techniques, potential selective group V sPLA2 inhibitors; lamellarin D and its analogs; novel lamellarin-campthothecin hybrid pentacyclic scaffolds, potential topoisomerase I inhibitors, and tetra- and pentacyclic heterocyclic skeletons, potential QR2 and aromatase inhibitors. This work is essential as it may lead to discovery of potent anti-inflammatory and anticancer agents. The methodological part of this proposal toward general and efficient methods for construction and functionalization of diverse fused heterocycles has even broader impact, as upon development, it would dramatically broaden the arsenal of libraries of biologically important molecules available for medicinal chemists and biologists, and will most certainly impact drug discovery research and related health-oriented sciences.


Elucidating the molecular characteristics of deltaFosB as a transcriptional activ


Human Aging, Exercise & FMD: Translational Physiology


Improvement of audio-visual speech recognition using multi-modal cooperation and integration techniques

本研究では、音声と発声時の口唇動画像を用いたマルチモーダル音声認識において、音声と画像それぞれの情報を相互利用する情報協調手法、および、音声と画像の情報を効果的にまとめる情報統合方法に関するさまざまな検討を通じて、マルチモーダル音声認識の認識性能の向上を試みた。その結果、認識性能の向上を達成しただけでなく、情報協調や情報統合に関する多くの新しい知識を得ることができた。


The avian influenza pandemic: the role of the media, science and government policy in forging public perceptions in the South.

At present, H5NI, the highly pathogenic strain ofAvian Influenza has been identified in 51 nations. The ability of the strain to foster a global human influenza pandemic is presently unknown. However, given the potential consequences of such an outcome, the Avian Influenza pan-zootic is gripping the world's media. Historically, the media has often been attributed a primary role in shaping public understanding of specific issues (Van Dijk, 1988; Sorenson, 1991; Fowler, 1991; Norris et al., 2003; Achugar, 2004; McCann- Mortimer et al., 2004). However, it is well known that despite the ethic of impartiality professed by journalists, the way in which information is presented often orients the reader towards specific values, ideas and/or an interpretation of events which is neither neutral nor objective (Sorenson, 1991). Therefore, the manner in which current outbreaks are portrayed is likely to influence public attitudes. Further, while the media is often utilised by governments to shape opinions, the media itself equally has a major influence on government policies. Within this milleau, science is often utilised to bolster arguments on both sides of any given debate. However, to date, little work has been undertaken which explores the inter-relationship between public policy, the media and science with regard to Avian infuenza.


No summary - Aucun sommaire

Natural Sciences and Engineering Research Council of Canada

Industrial Undergraduate Student Research Awards


Estudo da estabilidade de dispersoes de nanoparticulas em cristais liquidos.

O objetivo desse projeto é a investigação de propriedades dinâmicas e da estrutura microscópica de dispersões de nanopartículas em um meio anisotrópico. Nesse estudo serão utilizadas técnicas de espalhamento de raios-X, relaxação dielétrica, espalhamento de luz e observação de textura em microscópio de luz polarizada. As nanopartículas a serem utilizadas na preparação de soluções em cristais líquidos são inicialmente dispersas em água, podendo ser de origem comercial (Rhodia) ou produzidas em laboratórios de pesquisa. O meio anisotrópico a ser utilizado consiste em um cristal líquido liotrópico que apresenta fases nemáticas uniaxiais e biaxial em um largo intervalo de temperatura. Esses sistemas permitem uma abordagem tanto experimental como teórica para a compreensão das forças intermoleculares que governam a estabilidade de suspensões coloidais. Esse é um tema que aborda várias questões relevantes, seja do ponto de vista da físico-química seja do ponto de vista das aplicações industriais. (AU)

Fundação de Amparo à Pesquisa do Estado de São Paulo

Universidade de São Paulo (USP). Instituto de Física (IF)


Structure/Function of Varicella Zoster Virus DNA


WOUNDED WARRIOR SERVICE DOG PROGRAM

UNIFORMED SERVICES UNIVERSITY MEDICAL RESEARCH PROJECTS


Rapid hormonal modulation of feeding circuit dynamics and its disruption in obesity

PROJECT NARRATIVE The prevalence of obesity and metabolic disease continue to rise, and are thought to develop in part due to excessive consumption of carbohydrate-rich diets and impaired communication between the gut and the brain. We have previously shown that glucose infusion directly into the gut rapidly modulates the activity of feeding circuits in the hypothalamus and inhibits subsequent feeding, but the mechanism remains unclear. Here we propose using cutting-edge neuroscience and genetic techniques to determine the hormonal and neural mediators of these gut-brain dynamics, and to understand how obesity alters these pathways.


Algorithmic strategies for detecting structural variation in genomes

Project Narrative The proposed computational tools will be used to detect structural variations in human populations as a starting point for understanding their role in normal evolution and disease, specifically cancer. The architecture of tumor genomes will help reveal genes that are disrupted and di!erentially expressed in tumor cells. The targeted detection of genomic lesions in a heterogenous mix of mutated and wildtype cells, will find application as an early diagnostic for cancer. Thus, our computational methods will have an immediate and long term e!ect on human health.


Oligo-Vascular Crosstalk in the Developing Brain: Implications For White Matter Injury In Congenital Heart Disease

The proposed study will investigate cellular and molecular mechanisms of brain injury resulting from Congenital heart disease (CHD). Experiments will focus on oligodendrocyte-vascular crosstalk in normal development and how they support myelination and how they are altered in chronic hypoxemic conditions as seen in CHD to cause white matter metabolic dysfunction, maturation delay and injury


Regulation of adipocytes differentiation by marine lipids

Obesity is now recognized as a world wide problem. It is multiple risk factors for the life style-related diseases such as diabetes, hypertension, hyperlipidemia, and cardiovascular disease. Visceral fat accumulation plays crucial roles in the development of these diseases. So, it is important to prevent the life style-related diseases through significantly reducing excess accumulation of visceral fat. Fucoxanthin is a major carotenoid found in edible seaweed such as Undaria pinnatifida and Hijikia fusiformis. Fucoxanthin and its metabolite, fucoxanthinol, inhibited intercellular lipid accumulation and suppressed glycerol-3-phosphate dehydrogenase activity during adipocyte differentiation of 3T3-L1 cells. In addition, in 3T3-L1 cells treated with fucoxanthin and fucoxanthinol, peroxisome proliferators-activated receptor (PPAR_γ), which regulates adipogenic gene expression, was down-regulated in a dose-dependent manner. N-3 Highly unsaturated fatty acid, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which are major fatty acids in fish oil, also suppressed adipocyte differentiation of 3T3-L1 cells by down regulation PPAR_γ And C/EBP_α. White adipose tissue weight of mice fed fucoxanthin was significantly lower than that of mice fed control diet. Uncoupling protein 1(UCP1), a key molecule for metabolic thermogenesis, was clearly found in WAT of mice fed fucoxanthin. The anti-obesity effect of fucoxanthin was enhanced by the combination with fish oil containing DHA and EPA

Japan Society for the Promotion of Science


The Examination of Infection Prevention and Crowding in the Emergency Department

Healthcare associated infections (HAIs) are a major public health concern, despite being largely preventable. Millions of patients utilize the emergency department (ED) each year. During periods of ED crowding, patients are often exposed to unsafe conditions, which likely inhibit their receipt of guideline-based infection prevention care.  This study will be the first to examine infection prevention in the context of ED crowding and will  foreseeably demonstrate the need for improved evidence-based practices.


水溶液中の有機ハロゲン化合物類の溶解度と固体粒子への吸脱着挙動

ダイオキシン類の水溶液中の飽和溶解度および吸脱挙動の実測例は、社会的要求度の割には非常に少ない。しかも、難処理廃棄物の水洗処理の際に必要となる、塩類を含んだ系や酸、アルカリを含んだ水溶液での実測値は国内外ともにほとんど見当たらず、早急に測定値が求められている。そこで、本研究では、種々の塩類を含む水溶液中での有機ハロゲン化合物類の溶解度測定とそれらの水溶液中における物理化学的挙動に関して調査した。さらに、分子軌道法による水溶液中での溶質分子の電子状態計算から溶解度の推算を行い、実測値との対応を調べた。ジェネレータカラム法により3種のクロロベンゼン類、ビフェニルおよび8種のダイオキシン類の水溶解度の測定を行った。測定結果より、水溶解度と置換塩素数間に線形的な相関関係が見られた。水溶解度の温度依存性を5〜55℃を測定し、溶解エンタルピーを導出した。また、NaCl、KClおよびCaCl_2水溶液中(0-0.8mol/L)の水溶解度を測定し、以下のような塩析効果が得られた。K^+<Na^+<Cl^<2+>。COSMO-RS法により水溶解度を計算予測した。COSMO-RS法とは、連続誘電体モデルで分子軌道計算を行い、混合溶液中の分子間の相互作用エネルギーを見積もり、物性値を推測する方法である。その結果、室温の溶解度および温度依存性に関して、測定値と計算値間に良い整合性が得られ、多種異性体に渡る残留性有機汚染化合物の溶解度計算予測に利用できることがわかった。また、塩化物水溶液中の溶解度に関しても、強イオン性化合物に対してはモデルの改良が必要だが、COSMO-RS法によるある程度の予測の可能性が示された。また、フラスコ法により水中でのクロロベンゼン類のシリカ粉末および活性炭への平衡吸着量を測定し、粉末比表面積と吸着量の関係を得た。


Data Collection Methodology for Research Instrumentation

SCIENCE APPLICATIONS INTERNATIONAL CORPORATION


Nature of Mammalian Cutaneous Permeability Barrier


Comprehensive elucidation of the film growth and bonding mechanisms of ceramic coatings on different substrate materials via single particle investigation

Dense coatings had been developed on different substrates of metallic, ceramics, glass, and plastics. However, it is difficult to clarify the influence of substrate materials during the coating formation, where huge number of particles are deposited on substrate. This study proposes a new concept to clarify the substrate effect via elucidating: ① Investigates deformation, adhesion phenomenon, bonding mechanism of single particle. ② Develop 3D simulation modeling to validate the experimental hypothesis. ③ Process upgrading and integration to achieve strong adhesion on different substrates.

National Institute of Advanced Industrial Science and Technology


Vascular Ultrasound Analysis Workstation


ADRENAL CORTEX STEROIDOGENESIS--ENZYMOLOGY &CONTROL


RI: Small: Visual Parts for Image and Video Analysis

Images and video are analyzed in terms of parts. Qualitatively,
a part of an image is a region that can be extracted consistently, even if the image changes somewhat because of differences in quality, resolution, lighting, viewpoint, or small variations in the shape of the objects being depicted. In video, these regions are extruded into time, forming tubes of sorts that persist over relatively long time intervals.

Technically, parts are regions with high saliency and stability, two notions that are defined anew in this research based on mathematical tools that span from harmonic functions to new developments in computational topology and spectral graph theory.

Parts are a key handle into image and video structure, as they allow describing the visual information succinctly and in a stable manner. They lead to indices for retrieval, and provide primitives that make it possible for computer software to recognize objects and activities. The main result from this effort is a systematic comparison of advantages and limitations of the new definition with descriptors from the literature.

Applications of part-based visual analysis range from image retrieval, medical and biological imaging, and video interpretation for military and intelligence scenarios, to surveillance, the annotation and editing of images and video clips, and more. Work involves graduate students and undergraduates funded through the NSF REU program. Results of this research are disseminated through scholarly publications and classes at Duke University. A benchmark of evaluation images and video is developed for open use by the research community.


IMPROMALT: Improving winter malting barley quality and developing an understanding of the interactions of introgressions with genetic background

Maltsters, brewers and distillers are concerned about the long-term sustainability of the barley crop. Seasonal problems in many parts of Europe resulted in a restricted malting barley supply that has only just been alleviated by an above average harvest in Argentina. Within the UK, drought conditions resulted in reduced barley crop quality, i.e. higher protein samples, particularly in Eastern England, where much English malting barley is sourced. Under predicted climate change scenarios, such drought conditions are likely to become more frequent and will affect the spring crop much more than the winter crop, which can escape the worst effects of summer drought through a much earlier maturity. Whilst winter barley might therefore provide a more consistent supply, the proportion bought by English maltsters has declined by over 25% over the past 20 years. This decline is due to the reduced quality level of the winter crop compared to the spring so that distillers can produce 16 more litres of raw spirit per tonne of malt on average from the latter. For an industry predicted to use 600,000t of barley from the 2012 harvest, this is a highly significant difference in production efficiency.

All current UK winter barley malting varieties have been derived from Maris Otter, first recommended in 1965. Maris Otter combined the spring malting quality attributes of an older variety, Proctor, with the winter habit of Pioneer. Proctor was the major spring malting variety in the UK for many years but the introduction of Triumph was a quantum leap forward for the spring crop in terms of both quality and yield. In a previous project, we have analysed DNA fingerprints of UK spring and winter barley malting cultivars to identify genetic differences between the two crops that are associated with malting quality. Whilst plant breeders have previously tried to introgress spring quality attributes into winter barley, they have relied on chance events to assemble the right genes, which is an impossible task when the crops differ at thousands of genes. But we now have the knowledge and tools to conduct the introgression of spring attributes into winter barley in a highly targeted manner to test the hypothesis that their introduction will improve winter malting quality. The germplasm emerging from this proposal will then be used by the plant breeding partners of the project in further rounds of crossing and selection to develop improved winter malting quality cultivars that approached the spring quality levels but in a suitable agronomic background for contemporary farming practise and would thus re-generate interest in using winter barley for malting for use in brewing and distilling. As indicated in the previous paragraph, greater use of the winter crop is likely to provide a more consistent supply of malting barley in the future. As malting supplies are becoming tighter due to a variety of market factors, a switch to the higher yielding winter crop would also mean that the effects of competition for land for more profitable crops would have a less pronounced effect upon malting barley supply. As six row barley varieties tend to have a higher yield than two row, a longer term aim is to develop six row malting types that would further decrease the land area required to secure a malting barley supply.

Biotechnology and Biological Sciences Research Council


Funktionelle Charakterisierung von dynamischen Signalkomplexen der BRAF Kinase und deren Modulation durch tumorspezifische Mutationen und klinisch relevante KinaseInhibitoren

BRAF spielt eine zentrale Rolle bei der Aktivierung des RAS/ERK-Signalweges. Der Aktivierungszyklus dieser Kinase wird durch RAS-induzierte Homo- oder Heterodimerisierung, Protein-Protein-Wechselwirkungen und post-translationale Modifikationen (PTM) kontrolliert.In vielen Tumoren ist BRAF durch Mutationen dereguliert. Die häufigste Mutation, V600E, erzeugt einen Kurzschluss im noch unvollständig verstandenen BRAF-Aktivierungszyklus. Die BRAFV600E-Kinasedomäne befindet sich in einer Konformation, die von wildtypischem BRAF (BRAFWT) nur durch RAS-induzierte Aktivierung erreicht wird. Diese Erkenntnis führte zur Entwicklung von BRAFV600E-selektiven Inhibitoren, die z.T. beeindruckende Ansprechraten erzielen. Leider sind diese jedoch, durch das Auftreten von Resistenzen, oft kurzlebig. Die BRAF-Inhibitor induzierte, paradoxe Aktivierung des ERK Signalweges stellt einen häufigen Resistenzmechanismus dar. Dieses Phänomen wird durch die Eigenschaft von klinisch angewendeten, BRAF selektiven Inhibitoren verursacht, die die Ausbildung von Heterodimeren zwischen Inhibitor gebundenem BRAF und ungebundenen RAF Isoformen in RAS abhängiger Weise fördern. Hierbei wirkt inhibiertes BRAF als allosterischer Aktivator des Wirkstoff-freien RAF Protomers, wodurch ERK-Reaktivierung und Tumorwachstum begünstigt werden. Wahrscheinlich basiert die paradoxe Wirkung von BRAF-Inhibitoren auf Prozessen, die auch bei der physiologischen Aktivierung des Signalwegs auftreten. Insofern liefert die Aufklärung der räumlich-zeitlichen Dynamik von quaternären BRAF Komplexen im physiologischen wie pharmakologischen Kontext wichtige Beiträge zur Wirkstoffentwicklung.Unter Verwendung von Blue Native PAGE und SEC-PCP-SILAC basierter Massenspektrometrie (MS) konnten wir zeigen, dass BRAFWT und BRAFV600E Multiproteinkomplexe unterschiedlicher Größe und Zusammensetzung bilden. Zudem induzierte RAS BRAFWT-enthaltende Komplexe, deren Größe mit BRAFV600E Komplexen vergleichbar war. Interessanterweise, beeinflussen klinisch relevante Inhibitoren die Stabilität dieser Komplexe. Daher postulieren wir, dass der Aktivitätsstatus der Kinasedomäne die Anordnung von BRAF-Signalkomplexen bestimmt. In dem beantragten Projekt wollen wir diese Hypothese durch eine ausführliche Charakterisierung der Zusammensetzung und des PTM-Musters von BRAF-Komplexen, die unter physiologischen Bedingungen und in Gegenwart von Kinase-Inhibitoren mit (prä)klinischer Relevanz gebildet wurden, bestätigen. Wir werden unsere MS Protokolle mit neuartigen biochemischen Methoden kombinieren, um kurzlebige dynamische Interaktionen zu identifizieren. Unsere Studien sollen außerdem auf Komplexe von Nicht-V600E BRAF-Onkoproteinen ausgedehnt werden, die zunehmend durch Tumorsequenzierungen nachgewiesen werden und bisher kaum im Hinblick auf Ihre Wirkweise und Inhibitorempfindlichkeit charakterisiert sind. Hierdurch werden wir wichtige Informationen zum Pathomechanismus und zur pharmakologischen Blockade dieser Mutanten erhalten.


SYNTHETIC STUDIES RELATED TO CANCER RESEARCH/TREATMENT


ANTICARDIOLIPIN ANTIBODIES, BETA 2GI AND THROMBOSIS


Success and Vulnerability in America's Tropical Forests

Few tasks in science are more urgent than revealing the rules that govern why some living things dominate and which will be most vulnerable in our rapidly changing world. Most life on Earth is tropical, but understanding and predicting responses here is challenging. Amazonia, for example, still includes 5 million km2 of forest, nearly 20 times the size of the United Kingdom. South American forests are perhaps the most important ecosystems on Earth. They support astonishing diversity (15,000 tree species in the Amazon alone), lock up huge amounts of carbon (>100 billion tonnes), slow climate change, and support livelihoods (e.g., ter Steege et al. 2013, Phillips et al. 2017). How species and ecosystems here respond to climate change will define the future of life everywhere.

The aim of the project is to discover why some species are so much more successful than others, and if the rules of "success" are now changing.

This project takes advantage of three major developments in biodiversity science that make it possible to measure species' success and vulnerability in the most vital part of the planet (e.g., Enquist et al. 2016, Baker et al. 2017, Esquivel-Muelbert et al. 2017, Coelho de Sousa 2017). (1)biogeographical advances provide precision to map species and analytical tools let us model biogeographical records and their reliability. It is now possible to reveal species ranges and the climate and soil conditions they occupy. (2)ecological, long-term fieldwork to measure tropical species and dynamics is being integrated as never before, enabling assessment of abundance, biomass, growth and change over time (e.g., ForestPlots.net 2021). Thus it is possible to trace how successful species are, where, and in which conditions. Finally, (3)evolutionary scientists are piecing together the tree-of-life, the relatedness of everything, with extraordinary precision. Thus it is possible for the first time to explore how evolutionary history affects ecological success.

Focusing on the Amazon and adjacent dry and moist forests and savannas, key questions to develop include:

*Does biogeographic success predict ecological success? (For example, do well-distributed species also capture most carbon?).
*Is ecological success predictable from evolutionary history, or random across the tree-of-life? (For example, are forest dominants closely related to one-another?)
*Are species' climate-change-sensitivities written into their biogeography? (For example, are tree species from savannas and drier forests benefitting from recent climate changes, or are those phylogenetic clades that switched biomes in the past also those which are resilient now?).

The project will explore these and related questions working with leaders in these fields:

Remeasuring Amazon plots with partners in areas of rapid change.
Analysing long-term records of tree size, growth and death across neotropical forests.
Modelling species ranges from millions of records of occurrences and associated data.
Advanced biogeographic and evolutionary analyses, including visiting external partners Brian Enquist, founder of BIEN plant network, and Tiina Sarkinen, evolutionary scientist, for further training.

Potential for High Impact Outcomes
This project addresses key questions at the intersection of ecology, biodiversity, evolution, and climate change. It contributes to global understanding on what makes plants successful, or vulnerable - with potential for risk-profiling and developing conservation responses to help those at risk. The supervisors and collaborators have strong records of high-impact outcomes from research on tropical biodiversity, ecology, and carbon storage and sequestration.


Linking basal forebrain and entorhinal cortex vulnerability to preclinical Alzheimer's disease

Project Narrative To achieve early detection of Alzheimer’s disease (AD), which is critical for effective intervention, mechanistic models of preclinical AD pathological changes must be more comprehensive, incorporating all regions affected early in AD. The current proposal will use multiple approaches to demonstrate that two key AD-vulnerable regions historically studied separately, the basal forebrain and the entorhinal cortex, are affected similarly by early AD pathology with distinct cognitive consequences. This work will help to uncover drivers of AD-vulnerability in cortical and subcortical regions and to develop a more holistic understanding of preclinical AD, including variability in early cognitive decline.


Mass Spectrometric Studies of Spin Control in Open-Shell Molecules

The project involves mass spectrometry studies of the thermochemical properties of the reactivity of open-shell molecules and ions. The proposal describes studies designed to investigate the mechanisms through which electrons can interact in open-shell systems.  The goal of the work is to provide insight into how to control the spin of open-shell system by strategically choosing structural motifs that exploit the appropriate mechanistic aspects.  The three methods of controlling spin are:
1)	Topological approaches : the focus of this area is on disjoint diradicals and using connectivity to create them in either triplet or singlet states.  The role of topology will be investigated by contrasting the properties, such as electron affinities, of structurally related but topologically distinct bis-allylic diradicals.
2)	Heteroatom substitution : replacing a carbon in well-studied hydrocarbon diradicals with nitrogen or oxidized nitrogen can change the ground and excited state energy orderings.  This effect will be investigated by examining the thermochemical properties of pyridine- and pyridine-n-oxide based diradicals, determined by using energy-resolved collision-induced dissociation studies.
3)	Substitution : the electronic state ordering of aromatic nitrenes is altered by using substituents either on the aromatic ring or next to the nitrene center.  Negative ion photoelectron spectroscopy of substituted phenylnitrene radical anions will be used to investigate the electron affinities and the energies of the excited states in the neutral phenyl nitrenes.
Gas-phase studies of reactivity and structure can impact all areas of chemistry as well as other disciplines such as material science and engineering.  Mechanistic studies provide insight that can be used to develop new reactivity methodologies.  Whereas structural studies of open-shell species such as diradicals and triradicals provide insight into bonding and reactivity, they also provide a foundation for engineering and material science approaches to magnetic materials.  The work described in this proposal is also an important component of the education of a diverse and talented group of graduate students at Purdue University.  This support also allows the PI to utilize his experience with the NSF Graduate Research Fellowship Program to encourage and activities of the undergraduate students in the local ACS Student Affiliates and Alpha Chi Sigma chapters, particularly in regards to developing creative ways for the students to serve and impact the community.


Prevention of growth cone collapse in severed axons after a spinal cord injury, by inhibiting ROCK and by stimulating the cAMP/PKA pathway

The spinal cord consists of "electric cables", the axons, which connect the rest of the body to the brain. When these "cables" are severed due to a spinal cord injury, the consequences are disastrous: permanent paralysis of the arms and/or legs, loss of sensation, loss of control over critical body functions. Thus it is imperative that clinical treatments be developed to repair damage to the spinal cord. A major hurdle is how to stimulate the severed axons to grow across the site of injury, due to the presence of a multitude of inhibitory molecules which act on the tips of severed axons called the growth cones (GC). Inhibitors found at the injury site activate multiple signaling pathways causing GC collapse and failed regeneration attempt. Because it is impossible to individually block all inhibitors, I focus on interrupting the intracellular signaling pathways at a point of convergence. My targets are to inhibit the Rho protein and its downstream effector ROCK, and also to increase the cyclic nucleotide (cAMP) level in the GCs through pharmacologically manipulations. A specific cell-permeable inhibitor to ROCK, and another inhibitor to a cAMP-degrading protein, phosphodiesterase, will be used both in cell culture and in animal models to address their potential in therapeutic treatment of SCI. It is expected that these drugs will reverse the repulsive properties of the injured spinal cord environment and prevent the collapse of GCs. Hopefully, this new pharmacological approach will be useful in the clinical treatment of SCI.

Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships


STRUCTURES, INTERACTIONS AND DYNAMICS OF NUCLEIC ACIDS


Balancing Immunogenicity of a Tetravalent Live Attenuated Dengue Vaccine

PUBLIC HEALTH RELEVANCE: Dengue virus (DENV) infections are the leading mosquito-borne human viral disease globally with 2.5 billion people at risk, and 100,000,000 infections annually. Despite large investment over decades (both public and private) an effective vaccines has remained elusive. Here we will overcome limitations of previous dengue vaccine developments, by employing a novel synthetic biology method that allows for the more precise balancing of the immune response against the four individual serotypes in a new tetravalent dengue vaccine.


Therapeutic development of cystic fibrosis correctors

Cystic fibrosis is the most common fatal genetic disease. It affects at least 80,000 patients worldwide, imposing enormous burdens on the patient, their families and on society. Advances in early detection, antibiotic therapy and care have seen the median age for survival of CF patients increase to 37 years. However, despite the discovery 20 years ago, of the gene for CFTR and the most common mutation DeltaF508 causing CF, there is no therapy based on correcting the basic defect. It is known that the mutant DeltaF508CFTR protein is retained in the endoplasmic reticulum and does not traffic to the plasma membrane where it can function. We have developed an assay for screening "correctors" of this trafficking defect and isolated a variety of hit compounds that are effective in a variety of trafficking and functional assays that we have developed. In this collaboration with GlaxoSmithKline Inc., we will develop some of these compounds as therapeutics. As an orphan disease, CF has not been a priority with major pharmaceutical companies, thus this project is an excellent opportunity to combine the strengths and resources of university and pharmaceutical company expertise to develop a CF corrector therapy.

Operating Grant: Industry-partnered Collaborative Research - Rx&D partner


New Approach Methodologies for Assessing Neurodegeneration Risk from Food Contaminant Mixtures

neuroNAMix targets the critical nexus of food contaminants (FC) and neurodegenerative diseases using New Advanced Methodologies. Based on data science and in vitro methods, neuroNAMix aims to prioritise FCs for neurotoxic potential, explore their effects on cells and barriers interconnecting the gut and brain, and test new risk assessment approaches. It aims to provide food authorities and consumers with tools for a healthy and safer tomorrow.


Mecanismos fisiopatologicos da reversao do diabetes mellitus tipo 2 apos cirurgia bariatrica.

O aumento da prevalência da obesidade é acompanhado por um aumento do número de casos de DM2 (diabetes mellitus tipo 2), sendo que metade destes são atribuídos à obesidade. Para ambos, a cirurgia bariátrica é uma forma de tratamento. A perda de peso após a cirurgia é explicada pela restrição gástrica e má absorção intestinal decorrentes, porém o mecanismo do controle glicêmico não foi completamente elucidado. O fator mais evidente desta melhora seria a perda de peso, entretanto, foi demonstrado que o controle glicêmico a antecede, sugerindo que ele estaria relacionado primariamente à inanição do pós-operatório, que melhora da lipotoxicidade e da glicotoxicidade. Mas isto não explica completamente a reversão do DM2. Uma explicação mais interessante seria as alterações nos peptídeos gastrointestinais como a diminuição da grelina e o aumento do GLP-1 que teriam um efeito incretínico sobre a secreção de insulina. O objetivo deste trabalho é avaliar o potencial da cirurgia bariátrica em alterar os mecanismos fisiopatológicos do DM2, caracterizando as respostas das orexinas, anorexinas e incretinas endógenas a um teste de refeição padrão em obesos diabéticos e não diabéticos submetidos ou não à cirurgia bariátrica pela técnica de Gastroplastia Vertical com ""bypass"" gástrico em Y de Roux que tiveram e que não tiveram reversão do DM2, e ainda caracterizar a ação da insulina exógena neles. Serão selecionados pacientes do Ambulatório de Cirurgia de Obesidade do HC-UNICAMP em pré e pós-operatório. A análise do padrão de secreção hormonal nos diversos grupos será feita calculando-se a área sob a curva que correlaciona tempo de secreção e concentração plasmática de cada um dos hormônios, sendo estes valores comparados entre os grupos. Os resultados deverão contribuir para elucidar os mecanismos de reversão do DM2, assim como explicar porque a cirurgia bariátrica é incapaz de desativar estes mecanismos em pacientes que permanecem diabéticos. (AU)

Fundação de Amparo à Pesquisa do Estado de São Paulo

Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas (FCM)


Polychaete worm jaws - protein and metal for hard material


Promoting Student Education & Outreach at the 17th Annual Green Chemistry & Engineeering Conference

ABSTRACT

Green chemistry and green engineering offer fundamental sustainable solutions to the global challenges facing this planet. Green chemistry is the design of chemical products and processes that reduce or eliminate the use and generation of hazardous substances. Green engineering is the development and commercialization of industrial processes that are economically feasible and reduce the risk to human health and the environment. Green chemistry and engineering are absolutely essential to the development of solutions to global challenges. The impact of green chemistry and engineering approaches on sustainable development are significant, since these design philosophies unite the pursuit of economic prosperity with environmental and public health protection.

The annual Green Chemistry and Engineering Conference (www.GCandE.org) is organized each year by the American Chemical Society (ACS) Green Chemistry Institute® (ACS GCI) with the active involvement of an organizing committee comprised of scientists from other non-profit organizations, U.S. government agencies, academic institutions and industry. Dr. Jennifer MacKellar serves as the PI for the ACS Green Chemistry Institute.

The 17th Annual GC&E Conference in 2013 will have as its theme Sustainable Chemistry and Engineering in the 21st Century. Students participating in the GC&E workshop and/or conference will have a unique opportunity to engage in topics not commonly encountered in traditional university courses and conferences. The meeting is expected to convene a record number of approximately 700 plus leading international researchers from industry, academe, and government to discuss the latest advances in green chemistry and engineering from across the spectrum of the chemical enterprise. This dynamic event provides students with excellent opportunities to learn about the newest research developments across all topics of GC&E, dialog with other academic, industrial, and governmental researchers, and expand their network of professional contacts.


TRP Channel-Dependent Regulation of Arterial Tone (Renewal)

Project Narrative: The long-term goal for this project is to better understand molecular and cellular processes that control blood vessels and how these functions are affected by cardiovascular disease. Here, we describe a series of studies that will discover how a specific protein called TRPML1 affects the ability of vascular smooth muscle cells that make up the walls of blood vessels to properly contract and relax. We propose that TRPML1 enables a specific signaling pathway in these cells that promotes muscle relaxation and dilation of blood vessels. When this pathway is disrupted, blood vessels constrict more, leading to high blood pressure or hypertension. We will also study how TRPML1 affects the growth of smooth muscle during hypertension. A fuller understanding of these interactions may help to explain why blood vessels become dysfunctional in patients with hypertension.


Generation of Position Specific organoids to study human neuromuscular system development and disease

Locomotion results from the interaction between muscles and the nervous system. Dysfunction of such cells results in deadly diseases such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). These diseases often show regional selectivity but the underlying reasons remain obscure due to the lack of a suitable model system.  In previous work of my laboratory, we established a 3D neuromuscular organoid (NMO) model that allows the simultaneous generation of spinal cord neurons and skeletal muscle cells from human pluripotent stem cells (hPSCs) through a bipotent neuromesodermal progenitor (NMP). NMPs, located in the posterior part of the embryo, are driving axial elongation and coordinated growth of the trunk neuromuscular system. We coaxed hPSC derived NMPs to develop into neuromuscular organoids that form functional neuromuscular junctions supported by the presence of terminal Schwann cells and central pattern generator-like circuits. Thus, we are in the unique position to study in an organoid model the regulatory mechanisms involved in the formation and maintenance of the human neuromuscular system, and the disruption of these mechanisms in diseases. We will (i) identify the molecular requirements for the Generation of Position Specific (GPS) organoids representing distinct spinal cord segments, (ii) use NMOs to model and study ALS and SMA including the establishment of a drug screening platform and (iii) assemble hPSC-derived cerebral organoids and NMOs to include in the model human corticospinal tracts. In the long term, the information gained will have important implications for understanding and eventually treating neuromuscular diseases.

MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC)


ADD APP 21 ANG FACILITIES O&M

NATIONAL GUARD MILITARY OPERATIONS AND MAINTENANCE (O&M) PROJECTS


塵肺の発症における肺胞マクロファージの活性酸素産生と脱共役蛋白質の関係

塵肺の原因は粉塵暴露である。現在、吸入粉塵を貪食して活性化された肺胞マクロファージが活性酸素や活性窒素酸化物を放出し、これらが酸化的ストレスとなって肺の慢性炎症を惹き起こし、さらに線維化に至るという考えのもと、塵肺の発生機序について研究を進めている。マクロファージ系RAW264.7細胞およびJ774細胞を培養し、アスベスト(クリソタイルB,クロシドライト)またはその代替線維(グラスウール,ロックウール,セラミックファイバー)を加えて貪食させたところ、24時間後にはRAW264.7細胞およびJ774細胞いずれも多量の一酸化窒素(NO)を生じることを明らかにした。同時に、培養上清中にニトロソチオール(RS-NO)が増加することも明らかにした。この時、細胞内還元型グルタチオン(GSH)量は有意に減少し、従ってアスベスト等に曝露されたマクロファージはROS,RNSの生成だけでなく、細胞内の主要な抗酸化物質であるGSHの減少によっても酸化ストレスを受けることが示唆された。さらに、Wistar系雄ラットにクリソタイルを気管内注入し、24時間または48時間後の気管支肺胞洗浄液および血漿中RS-NO量を測定した結果、いずれもクリソタイル注入群で有意に高値を示した。このことから、クリソタイルの気管内注入により、肺内のみにとどまらず、生体内のあらゆる器官における酸化ストレスが増大する可能性を示した。また、RAW264.7細胞およびJ774細胞にクリソタイルおよびロックウールを加えた場合、3時間後からスーパーオキシドアニオン(O_2^-)の産生が有意に増加することを明らかにした。そこで、RAW264.7細胞にクリソタイルを添加後24時間の脱共役蛋白質(UCP)-2発現量を測定したところ、クリソタイル添加群でUCP-2発現量の増加傾向が見られた。このことから、クリソタイルを貪食したマクロファージ系RAW264.7細胞においては、ミトコンドリアの呼吸鎖における酸化的リン酸化に関与するUCPの発現量が増加することによりO_2^-産生が増加している可能性が示唆された。

Japan Society for the Promotion of Science

Otemae Junior College(2005)Hyogo Medical University(2004)


Kalamazoo Community Clinical Oncology Program


Theoretische und experimentelle Untersuchungen zur Pulsfrontverformung für die Lasermaterialbearbeitung mit ultrakurzen Laserpulsen

In unterschiedlichsten Anwendungsgebieten hat sich im Laufe der letzten Jahre der Einsatz ultrakurzer Laserpulse etabliert, um verschiedenste Werkstoffe mit hoher Präzision zu bearbeiten. Durch die Reduzierung der Pulsdauer lässt sich bei gleichbleibender mittlerer Leistung eine höhere Leistungsdichte erzielen, die die Anregung nichtlinearer Prozesse und somit eine effiziente Absorption der Laserstrahlung ermöglicht.In Kombination mit Scansystemen lassen sich großflächige Werkstücke mit hohen Prozessgeschwindigkeiten bearbeiten, da sich hohe Vorschubgeschwindigkeiten und Beschleunigungen des fokussierten Laserstrahls gegenüber dem Werkstück realisieren lassen.Bei der Propagation von ultrakurzen Pulsen durch dispersive optische Elemente tritt, aufgrund des Unterschieds zwischen Gruppen- und Phasengeschwindigkeit, eine Verzögerung (Propagation Time Difference bzw. PTD) zwischen Puls- und Phasenfront auf. Propagiert z. B. ein Puls achsparallel durch eine Positivlinse, tritt die größte Verzögerung entlang der optischen Achse auf, während die Verzögerungen entlang der Randstrahlen aufgrund geringerer Glasdicke minimal werden. Im Fokus führt dieser Effekt zu einer effektiv höheren Pulsdauer. In der Literatur werden Verfahren diskutiert, die eine Kompensation des Effektes für Systeme mit achsparallelem Lichteinfall ermöglichen.Sowohl die simulativen als auch die experimentellen Vorarbeiten zeigen, dass die PTD stark von dem Feldwinkel abhängt und bei Objektiven für Laserscanner zu scanwinkelabhängigen Pulsdeformationen und Pulsdauern führt. Ersten Simulationen lässt sich entnehmen, dass für vergleichsweise kleine Scanwinkel von 6° bei konventionellen Scanneroptiken bereits Pulsausdehnungen in der Größenordnung von 100 fs auftreten. Bei sensitiven Prozessen, wie z. B. der Bearbeitung von transparenten Dielektrika mit Pulsdauern im Bereich von 500 fs, sind durch die Variation von Pulsform und -dauer scanwinkelabhängige Bearbeitungsergebnisse zu erwarten.Ziel ist die Entwicklung neuer Konzepte und Methoden im Optikdesign, um Fokussieroptiken für Laserscanner mit homogenen Pulseigenschaften im gesamten Scanbereich auszulegen.Das geplante Arbeitsprogramm gliedert sich in die Bereiche Modellierung/Simulation, Konzepte/Designmethoden und experimentelle Validierung. Zu den Arbeiten im Bereich Modellierung/Simulation gehört die Untersuchung unterschiedlicher Strahlen- und Wellenoptischer Verfahren auf ihre Gültigkeit im Hinblick auf die Beschreibung von Pulsdeformationen hinter Fokussieroptiken. Gleichzeitig soll ein Messverfahren aufgebaut werden, um die Pulsfront für unterschiedliche Feldwinkel an Scanner-Objektiven messen und mit den Ergebnissen der Simulation vergleichen zu können. Darauf Aufbauend werden unterschiedliche Designmethoden verfolgt und mit geeigneten Verfahren aus der Simulation verknüpft. Abschließend ist die experimentelle Validierung beispielhaft ausgelegter Objektive u. a. durch Versuche in der Bearbeitung von Glasproben geplant.


Anatomical Plasticity and HPA Axis Dysfunction


Role of extracellular vesicles in the outcome of CAR T cell therapy in cancer

Chimeric antigen receptor T (CAR-T) cell therapy has significantly advanced cancer immunotherapy for haematological malignancies by redirecting the cytotoxic activity of patient T cells to tumour cells. Application of CAR-T technology for haematological and solid cancers is the focus of intense clinical research currently. While in some patients CAR-T infusion leads to complete and sustained clearance of the cancer, a significant proportion have primary resistance to treatment or fail to achieve durable clinical responses. Efficacy in solid tumours has not met the success levels seen in liquid cancers. There is a clear need for better understanding of CAR-T cell function to increase clinical success.

Outcome This project will establish the metabolic basis of CAR-T cell motility investigating both environmental and cell-intrinsic metabolic factors. Finally, we will uncover the role these factors may play in therapeutic response.


Towards a grounded theory of knowledge intrapreneurship.

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung


木材腐朽菌のフェニルアラニンアンモニアリアーゼのリグニン分解過程での役割

前年度に引き続き、木材腐朽菌Phenerochaete chrysosporiumの二次代謝産物Veratryl alcohol(VA)の蓄積が、培地へのフェニルアラニン添加により阻害される機構を明らかにするために、フェニルアラニン、又、アンモニウムイオンの添加がアンモニア同化酵素(L-Glutamate:NADP^+ oxidoreductase,EC1.4.1.4(GDH),L-Glutamate:ammonia ligase,EC6.3.1.2(GS))活性に与える影響を検討した。まず、培地に添加したアンモニウムイオン、又、フェニルアラニンは、添加後5日、又、7日で代謝され培地より消失した事を見出した。フェニルアラニンの減少と、誘導されるフェニルアラニンアンモニアリアーゼ活性(PAL)は同期していたため、菌体は、PAL活性が高い時期に、フェニルアラニンからの窒素を獲得できたと考えられた。しかし、フェニルアラニン、又、アンモニウムイオン添加数時間後のGS,GDH活性には変動が観察されなかった。その点に関し、菌体内の窒素代謝の様相を解明するには、本研究のように酵素活性の変動の検討だけでは限界があると考えられた。その間、米国のTowersらが^<15>N標識したアミノ酸を用い、木材腐朽菌Lentinus lepideusにおいて、フェニルアラニンアンモニアリアーゼを中心とした窒素のリサイクル機構を、^<15>N-NMRを用い報告した。この^<15>N標識化合物を用いる方法は、本研究で行っている酵素活性の変動から考察する方法に比べ、菌体に対するアンモニウムイオン、フェニルアラニン添加の影響を検討する点においては適当な方法ではないかもしれないが、リサイクルの証明には最も強力な方法と考えられた。しかしながら、助成を受ける間には、実験を進めることはかなわなかった。現在、これまでの結果を取りまとめているところである。


Using Targeted Lipid Nanoparticles to Deliver Chemotherapeutic Agents against  Pancreatic Cancer

Project Narrative This proposal develops targeted drug carriers for precise delivery of anticancer drugs to pancreatic cancers. These carriers achieve high drug concentrations in tumors and minimal concentrations in healthy tissues, resulting in enhanced tumor destruction and reduction of adverse effects of anticancer drugs. These drug carriers extend the lifespan and enhance the quality of patients’ life.


Sex-Based Differences in Post-Infarction Remodeling


The role of the endocannabinoid system in regulating hepatic glucose fluxes

Narrative: It is well established that a tight relationship exists between obesity and type 2 diabetes. Weight gain worsens glucose control and conversely, weight loss improves glycemic control and thereby decreases the risk of diabetic complications. Here we wish to understand how hormones that play important roles in energy homeostasis, leptin and endocannabinoid control glucose homeostasis advancing our understanding of pathophysiology and treatment of diabetes.


Epigenetische Mechanismen vermitteln adaptive epitheliale Resilienz zur Förderung der Darmregeneration

Das Darmepithel stellt die erste physische Abwehrbarriere gegen Umwelt- und mikrobielle Angriffe dar und ist ständig einer rauen Verdauungsumgebung ausgesetzt. Unterschiedliche gastrointestinale Erkrankungen beruhen auf einer gestörten Barriere und Regeneration. Die epitheliale Integrität kann durch Faktoren wie Infektionen, Dysbalance kommensaler Bakterien, Stoffwechselprodukten, bis hin zum Lebensstil (z. B. Alkoholkonsum, Ernährung) beeinträchtigt werden, und die Grundlage für ein Spektrum von Krankheiten wie Krebs und chronischen Entzündungen bilden. Ein tiefgreifendes Verständnis regenerativen Mechanismen zur Gewährleistung der epithelialen Schutzfunktion ist unerlässlich, um wirkungsvolle Behandlungsstrategien für Magen-Darm-Erkrankungen zu entwickeln. Schnelle regenerative Prozesse schützen den Organismus nach Schädigung des Darmepithels. Die Wiederherstellung der Gewebearchitektur und Barrierefunktion nach Epithelschädigung erfordert eine zelluläre Reorganisation und Aktivierung regenerative Prozesse. Das Darmepithel weist eine hohe Regenerationsfähigkeit auf und kann die epitheliale Architektur rekonstruieren. Dieser Regenerationsprozess wird durch eine hohe Plastizität der Epithelzellen ermöglicht. Diverse Vorläuferzellen sowie terminal differenzierte Epithelzellen können in diesem Prozess in Stammzellen reprogrammieren, aus denen neues Epithel regeneriert wird. In vorangegangenen Studien konnten wir die Rolle des epigenetischen Modifizierers MLL1 in der Spezifikation von Epithelzellen und in der Kontrolle von Krebs-Stammzellen aufklären. Hingegen ist die Bedeutung von MLL1 bei der Regeneration bisher nicht verstanden. In der Haut wurde gezeigt, dass epigenetische Regulationsmechanismen bei wiederholter Schädigung ursächlich für eine schnellere Wundheilungsreaktion sind. Diese Daten implizieren eine Art epithelialer Gedächtnisfunktion, die durch Entzündungsreize ausgelöste wird.  Wie während bzw. durch entzündliche Bedingungen die Plastizität intestinaler Epithelzellen induziert wird, und wie Darmepithelzellen in Stammzellen reprogrammieren ist nicht verstanden. Ob epigenetische Mechanismen ebenfalls an diesem Prozess beteiligt sind und ob sie die Aktivierung von regenerationsregulierenden Genen erleichtern ist ebenfalls nicht geklärt. Mit der Unterstützung dieser Forschungsförderung soll die Rolle des epigenetischen Regulator MLL1 bei der Regeneration nach Epithelschädigung und entzündlicher Darmerkrankung aufgeklärt werden. Es soll aufgeklärt werde, ob Darmepithelien Anpassungsfähigkeiten auf wiederholten Gewebeschädigung aufweisen und ob ein entsprechendes epitheliales Gedächtnis, sowie regenerative Programme durch den epigenetischen Modifizierer MLL1 vermittelt werden. Darüber hinaus wird diese Studie untersuchen, ob eine Ursache einer entzündlichen Kolitis beim Patienten ein Überschießen eines epithelial-intrinsischen Anpassungsprogramms ist.


Big Data Value Spaces for COmpetitiveness of European COnnected Smart FacTories 4.0

EFFRA recommendations on Factories 4.0 and Beyond (Sept 2016) clearly stated the need for development of large scale experimentation and demonstration of data-driven “connected smart” Factories 4.0, to retain European manufacturing competitiveness. BOOST 4.0 will address this need, by demonstrating in a measurable and replicable way, an open standardised and transformative shared data-driven Factory 4.0 model through 10 lighthouse factories. BOOST 4.0 will also demonstrate how European industry can build unique strategies and competitive advantages through big data across all phases of product and process lifecycle (engineering, planning, operation, production and after-market services) building upon the connected smart Factory 4.0 model to meet the Industry 4.0 challenges (lot size one distributed manufacturing, operation of zero defect processes and products, zero break down sustainable operations, agile customer-driven manufacturing value network management and human centred manufacturing). Our chief objectives include:
(1) Establish 10 big data lighthouse smart connected factories (VW, FILL, AutoEuropa, +GF+, FIAT, Phillips, Volvo, GESTAMP, Benteler, Whirlpool).
(2) Provide the RAMI 4.0 and IDS based BOOST 4.0 open EU framework and governance model, for both services and data assets.
(3) Put together methodologies, assets, models and communities in order to maximise visibility, mobilization, replication potential, and impact (business, financial, standardization) of BOOST 4.0
The investment leveraging factor of BOOST 4.0 will be well above the 4:1 ratio, up to 10:1. In terms of exploitation, in 5-years horizon after the project end, just only the participating lighthouse factories will make a direct follow-on investment above 33Meuro (ROI 10,61), while the commercialisation of the BOOST 4.0 products in the market is expected to generate some 96Meuro cumulative profits  (ROI 4,73) for the rest of the partners.

H2020 LEIT Information and Communication Technologies


"STRUCTURE AND OPTICAL PROPERTIES OF NOBLE METAL NANOPARTICLES " (THE GRANTEE'S TECHNICAL PROPOSAL)  DATED  21 JULY 2008 THE RESEARCH TERMS AND CONDI

AIR FORCE DEFENSE RESEARCH SCIENCES PROGRAM


Predicting Pediatric Readmission: Development of a Validated Risk Prediction Tool

NARRARTIVE After leaving the hospital, many children will need to be rehospitalized within a month. The results of this study will enable clinicians and researchers to predict which children are most likely to return to the hospital. Understanding which children are at risk, will allow for increased hospital to home transition support to prevent unnecessary hospitalization.


KoKonstruktion von Erklärungen mit emotionaler Ausrichtung zwischen KIErklärer und menschlichem Adressaten

In sozialen Interaktionen sind emotionale Reaktionen unvermeidbar. Die dem Projekt A03 zugrunde liegende Annahme ist, dass emotionale Hinweise des Adressaten ein wichtiges Feedback für den Erklärenden sind. Außerdem beeinflussen Emotionen den menschlichen Verstehensprozess, was sich in den Fragen widerspiegelt, die ein Adressat stellt. Das Ziel dieses Projekts ist die technologische Entwicklung eines emotionsbasierten Modells des Verstehens, das die Entscheidungsfindung von Adressaten unterstützt.


Kiskinowâpamew (s/he imitates her/him in order to learn): An Indigenous-led organization's research journey

Social Sciences and Humanities Research Council of Canada

Indigenous Research Capacity and Reconciliation - Connection Grants


WISCONSIN'S ENVIRONMENTAL PUBLIC HEALTH TRACKING NETWORK IMPLEMENTATION


MOLECULAR APPROACHES TO PEDIATRIC SCIENCE - CHRC


NEUTROPHIL ACTIVATION AND EXPRESSION OF SURFACE ANTIGENS


Development of hemoglobin-based blood substitutes


Development of a New Method for Circuit Complexity Based on Large Scale Mathematical Programs

論理回路モデルを代表とする各種計算モデルに対する, 論理関数の計算量の下限導出手法に関する研究を行った. 特に, 計算量下限導出問題を大規模数理計画問題へと帰着するアプローチについて重点的に研究を行った. その結果, 限定乱雑性を持つ論理関数に対する論理回路のサイズや, 多数決関数を近似する論理関数に対する定数段数論理回路のサイズの漸近的値を明らかにすることに成功した. 更には, 単キュービット量子回路に対して, その表現の一意性が担保される正規形の概念を提案したる.

Japan Society for the Promotion of Science


Sexual Violence Prevention and Education


Developing a whole-genome sequencing method for single human cells

We propose to develop a whole-genome sequencing method for single human cells and apply it to study clonal diversity in a breast tumor sample. This study is directly aligned with the interests of the Single Cell Analysis Program (SCAP) to develop new technologies to study genomics in single cells and with the mission of NIH to decreased morbidity in breast cancer through the development of new methods to diagnosing and detecting tumor cells. The single-cell sequencing tools developed in this grant are also highly relevant to public health because they will have a broad positive impact on many other human diseases, including neurological disorders, infectious disease, immunological diseases and developmental disorders.


Mechanisms of Double-strand Break Repair in Yeast


9625549  Prange  This grant supports work of this senior, distinguished  theorist whose past contributions have ranged over a variety  of diverse areas in condensed matter physics.  More recently  the PI has been involved in the general area of quantum  nonlinear science.  This subject, on the interface between  quantum disorder problems and such nonlinear properties as  chaos and fractals is expected to have strong influence on  the emerging fields of nanoscale devices.  The PI has been  instrumental in a major conceptual advance in this field,  namely the removal of the divergence in a quasiclassical  approach.  This grant will further develop the applications  of the quasiclassical approach.  In another project the PI  will explore the synergism of the random matrix theory and  the quasiclassical methods in their application to the  properties of disorder at quantum scale.  %%%  Small scale (nanoscale) devices have properties whose  description sometimes poses a special mathematical  challenge.  In this continuing work of a distinguished  theorist, attempts are being made to try a variety of modern  mathematical techniques, such as random matrix theory and  quasiclassical approximation in search of a effective and  efficient computation of the material properties.  This work  will advance the state of quantum nonlinear science.  ***


Development of Tunable Squeezed-light Source and Its Application to Spectroscopy

We generate amplitude squeezed light tunable around 430nm using a frequency-doubling ring cavity with a KNbO_3 crystal. The cavity is pumped by a single-frequency Ti : sapphire laser, which is pumped by a frequency-doubled all solid-state Nd : YVO_4 laser. The degree of squeezing is O.2dB at 20MHz with second harmonic (fundamental) power of 95mW (300mW). The observed degree of squeezing is consistent with theoretical calculation applicable to our cavity, but smaller than a previously reported value. We also study the optical properties of CuCI and ZnCdSe quantum dots, for future application to solid-state spectroscopy with squeezed or nonclassical light.


高度好塩菌の光エネルギー変換分子;バクテリオロドプシンの機能と構造

高度好塩菌のバクテリオロドプシン(BR)は細胞膜に存在し、光駆動プロトンポンプの機能を持つ、即ち、光エネルギーを電気化学的エネルギーに変換する一種のエネルギー変換素子である。BRが光を吸収すると、数種の吸収スペクトルの異なる中間体を経て元に戻る。この光反応に伴ってプロトンが膜の一方から他方へ運ばれる。本研究ではこのプロトンポンプの分子機構を明らかにすることを目的とした。本年度は酵素(キモトリプシン)処理したBR(以下ch-BR)及び未処理BR(native BR)を用いて中間体の生成・崩壊、プロトンの取り込み等について比較検討した。M中間体の崩壊は速度定数の異なる2成分から成る。遅い成分の速度はch-BRでは遅くなっているのに対し、速い成分の速度は両者で大きな差がない。M中間体の両成分の量の温度依存性を比較すると、速い成分については、ch-BRでは温度が高くなるほど増加する傾向にあるが、nativeではほとんど変化しない。また、遅い成分については、native BR.ch-BR共に温度が高くなるほど減少する。M中間体の崩壊の速い成分の速度とO中間体の生成速度はすべての温度でほぼ一致する。しかし、O中間体の量は温度が高くなるにつれて増加していくのに対し、M中間体の速い成分の量はほとんど増加しない。これは吸光係数の温度変化だけでは説明できず、M中間体の崩壊の速い成分に2つあり、O中間体を経る成分と直接BRに戻る成分のあることを示唆する。ch-BRもプロトン活性を持つ。プロトンの膜への再吸着速度はnative BRとch-BRでほとんど差が見られない。プロトンの吸着量の温度依存性を見ると、共に温度が高くなるにつれ、その量が減少している。しかし、ch-BRではプロトン輸送の効率が低下している。M中間体の遅い成分の量とプロトンの量は共に温度が高くなるほど減少していることから、プロトンはM中間体の遅い成分に伴って取り込まれていると考えられる。


9.4テスラ小動物用高磁場撮像装置を用いた急性頸髄損傷の包括的探索

本研究では、超急性期の外傷性頸髄損傷による死亡例を対象とし、剖検により採取された脊髄を固定後、9.4テスラ小動物用高磁場撮像装置を用いて撮像する。得られた画像とMRIパラメータを剖検所見と照合し、死因となる急性頸髄損傷の病態を包括的に探索するものである。解剖執刀医の解釈が分かれる肉眼的所見や、受傷から死亡までの経過が短いために判然としない病理組織学的所見だけなく、MRIによって得られる定量的数値を元にした、客観的な死後診断プロセスの確立を目指す。


Chromatin's Role in Repair of Radiation-induced Damage.


Instructional Scientific Equipment Program


Epidemiologic Research on Screening for Vestibular and Balance Disorders

PUBLIC HEALTH RELEVANCE: This study will develop and evaluate new screening tests of the vestibular system (inner ear) in a well- controlled environment and then in field tests at less controlled sites, for eventual use in performing public health studies of the American population to determine the frequency of occurrence of inner ear problems in the population. These tests will also be useful for screening people who have symptoms of inner ear problems in nursing homes and other environments where sophisticated diagnostic testing is not available, including astronauts at distant landing sites when they return from space flight. Using these tests may also provide more information about the effect of HIV/AIDS on the health of the inner ear.


Vroegsignalering van betalingsproblemen in het mkb

Optreden voordat schulden ontstaan

Het vangnet voor ondernemers in financiële problemen (BBZ) werkt niet optimaal. Bij een belangrijk deel van de gevestigde en oudere ondernemers is het maatschappelijk rendement negatief (Kok, Croon, Scholte en Tempelman, 2018). Ondernemers in de BBZ stoppen eerder met hun bedrijf en/of gaan er in inkomen op achteruit in vergelijking tot eenzelfde controlegroep.

Vroegsignalering kan de instroom in de BBZ reduceren. Daarbij is de rol van financiële adviseurs en/of coaches cruciaal. Zij zijn de meest geraadpleegde partij bij financiële ondersteuning (Van der Veen, Van Teeffelen, Ibrahimovic en Lentz, 2015). Tegelijkertijd geven financieel adviseurs/coaches aan dat zij niet tijdig zien aankomen dat een ondernemer betalingsproblemen heeft of krijgt.

Om betalingsproblemen te voorkomen is beter zicht nodig op de interactie van zakelijke en private risicofactoren. Er zijn geen onderzoekpublicaties bekend die de zakelijke en de privésituatie van de ondernemers in samenhang bespreken. Ook uit de praktijk van onze consortiumleden blijkt dat zij óf de zakelijke óf de privésituatie kunnen overzien. Niet beiden. Er is daarmee een blinde vlek voor financieel adviseurs/coaches in hun signaleringsrol.

Wetenschappelijk onderzoek richt zich vooral op grote bedrijven met beursnoteringen. Wat ontbreekt zijn geteste voorspellers voor het mkb om betalingsproblemen te signaleren. Daarnaast willen financiële adviseurs en coaches weten welke interventies effectief zijn.

Ons project beoogt:

1.      De risicofactoren, een risicomatrix - zakelijk en privé - en de handelingsmogelijkheden van ondernemers in kaart te brengen.

2.      De risicomatrix en belemmeringen tot handelen intern en extern te valideren.

3.      Twee eenvoudige preventieve interventies met ons consortium te ontwerpen.

4.      De effectiviteit van deze twee interventies te testen.

Daarmee worden financieel adviseurs, coaches en toekomstige beroepsbeoefenaars - onze studenten - beter toegerust om betalingsproblemen bij ondernemers te voorkomen. De opgedane kennis wordt verspreid bij vier brancheorganisaties, meerdere landelijke platforms en drie hogescholen.

Nederlandse Organisatie voor Wetenschappelijk Onderzoek


空間グラフの位相幾何学的研究

1.Conway-Gordonは6頂点完全グラフの3次元球面への任意の埋蔵は分離しない絡み目を含むことを示した。 この結果の一般化として(2n+3)次元単体のn-骨格の(2n+1)次元球面への任意の埋蔵は2つのn次元球面からなる分離しない絡み目を含むことを示した。2.大山淑之氏(名古屋工業大学)との共同研究において空間グラフ内の結び目のバシリエフ不変量達の間の関係について考察した。3.安原晃氏(東京学芸大)との共同研究において空間グラフ内の結び目・絡み目の実現問題について研究した。4.Przytycki氏(George Washington University)との共同研究においてBrunnian絡み目のHOMFLY-PT多項式について研究した。5.高々可算個の単体からなる任意の1次元局所有限単体Xと任意の自然数nについてXの互いに交わらず互いに同相なn個の部分空間でそれらの和集合がXになるものが存在することを示した。6.安原晃氏(東京学芸大)との共同研究において結び目の局所変形とバシリエフ不変量に関する葉広和夫氏(東大)の定理の一般化を行った。


Aromatic Cations and  Aromatic Cyclization


We have tried to think about Insolvency Practitioner(IP) from historical point and comparative point, particularly,insolvency court, insolvency lawyer, debtor and creditor. As time went by, the role of Insolvency Practitioner has changed. We can understand that the role of Insolvency Practitioner is influenced by the purpose of insolvemcy proceedings.


METABOLISM AND FUNCTION OF COMPLEX LIPIDS


Layer-Specific Functional & Perfusion Imaging of Retina


The physiological relevance of bile pigments

Bilirubin; Biliverdin; Antioxidant; Anti-mutagenicity; Anti-carcinogenicity; Vasoprotection


Impact of Drug Policy Reform on the HIV Risk Environment among IDUs in Tijuana

We propose a longitudinal, mixed methods study to address the impact of Mexican drug policy reform on the following outcomes among IDUs in Tijuana over time: 1) Changes in knowledge, attitudes and experiences about the enactment of Mexican drug policy reform and their relation to drug using behaviors and treatment readiness; 2) Temporal trends in drug use behaviors; 3) Health risks and protective behaviors; 4) Experiences with drug treatment: i) proportion of drug users over time choosing treatment over incarceration; ii) incidence and experiences with voluntary and involuntary drug treatment and 5) Law enforcement practices and interactions with IDUs. To address these aims, we will recruit a cohort of 750 IDUs in Tijuana who will undergo semi-annual quantitative interviews and testing for HIV antibodies. At each visit, a sub- sample who report receiving a 1st, 2nd or 3rd strike for drug possession will undergo qualitative in- depth interviews to address the context of their knowledge of the law (Aim 1), changes in drug use and health risks (Aims 2&3) experiences with drug treatment (Aim 4) and police (Aim 5).


腎薬物トランスポータ遺伝子多型に基づいた炭酸リチウム副作用発現予測

Principal Investigator：赤嶺 由美子, Project Period (FY)：2016, Research Category：Grant-in-Aid for Encouragement of Scientists, Research Field：薬学Ⅰ


RESEARCH TRAINING IN INTERVENTIONAL RADIOLOGY


Synthesis and catalytic properties of ruthenium amido complexes

No summary - Aucun sommaire

Natural Sciences and Engineering Research Council of Canada


Solutions for constructions and bulding MAteRials based on The eNeRGy absorption

Energy efficiency in buildings is a critical aspect of addressing climate change and reducing greenhouse gas emissions. To contribute to this endeavor, our research project focuses on the development and optimization of phase change materials (PCMs) derived from biomass as a sustainable solution for thermal energy storage in buildings. PCMs have shown promise in enhancing energy efficiency by storing and releasing thermal energy as they undergo phase transitions. However, challenges such as low thermal conductivity and leakage have limited their widespread application, especially in construction materials. Our project seeks to address these challenges by exploring the use of natural biomass materials, such as plant fibers, wood particles, endocarps, and husks, as containers for PCMs. These lignocellulosic materials possess unique properties, including high deformation capacity and porosity, which make them promising candidates for effectively containing and activating PCMs. By utilizing biomass as PCM containers, we aim to improve the thermal performance of building materials, reducing energy consumption and greenhouse gas emissions. To achieve our objectives, we will conduct a comprehensive research program that includes experimental testing, numerical simulations, and optimization techniques.

HORIZON EUROPE Marie Sklodowska-Curie Actions


PERSONALITY DISORDERS, GROUP THERAPY AND CHANGE


Organ-specific autoimmunity resulting from two genetic defects in tolerance

Project Narrative Most human autoimmune disease is believed to result from genetic susceptibility combined with environmental or stochastic events resulting in a break in immune tolerance to a limited number of components of the individual. In this project, we shall use a new digenic mouse model of spontaneous organ-specific autoimmune disease, directed against an eye autoantigen, to determine in detail how defects in two different immune tolerance pathways can interact to create disease susceptibility. These studies will provide insights into the nature of the genetic inheritance of susceptibility to autoimmune disease and how disease is initiated.


The dynamics of fluid flow, fluid mixing and ore mineralization in the Navan Ore body.

In order to be successful in exploration in an increasingly competitive environment, interdisciplinary research with new innovative ideas is clearly needed. This project merges state-of-the-art numerical models of fluid flow, mixing and mineral precipitation with one of the best geochemical datasets that is available from a structurally controlled world-class ore deposit. The structural control at Navan deposit in Ireland implies that fluids travel along faults and fractures, however, horizontal stratigraphy-controlled flow has also been observed. It is not clear in detail how faulting, fluid flow and mixing influence the ore precipitation. In addition it is not clear how the metal-bearing fluids enter the system, multiple pathways exist at the level of the mine, but does this pattern represent multiple deeper sources or one pathway?
The main objectives of this study are to understand fluid flow, fluid mixing and consequent ore mineralization in the Navan ore-body in Ireland, in order to predict the potential location of additional resources. Based on previous work, the hypothesis is that metal-carrying fluids from a deep source move up in semi-vertical pipes in the footwall of a larger fault system and then spread out horizontally into the sedimentary host to form the large ore deposits when the deep fluids mix with a shallow brine, charged with bacteriogenic sulphide. The student will combine novel numerical modeling techniques with a detailed analysis of a world-class 3D dataset of the distribution of mineralization and isotope data in the Navan ore body coupled with a detailed microstructural study of the local ore structure.


Diabetes is a growing epidemic associated with severe comorbidities including heart disease, stroke, non-traumatic amputations, and kidney disease, significantly reducing life expectancy, and imposing substantial economic and healthcare burdens. Available treatment options largely manage symptoms of the disease rather than addressing underlying causes, and there is presently no cure. Dr. Prentice aims to take an integrative physiology approach to unravel the mechanisms underlying diabetes pathogenesis. Diabetes is a multifactorial disorder that involves dysfunction of numerous tissues long before disease onset. Her goal is to understand the complex interplay between insulin-producing beta cells and insulin-responsive tissues, such as the liver and fat, during the prediabetic period to uncover disease mechanisms and identify therapeutic targets. While most studies focus on comparing individual tissues between healthy and diseased states, Dr. Prentice's work will use innovative strategies to explore communication between numerous tissue types over the time course of disease development. She hypothesizes that factors secreted from fat and liver in the prediabetic period actively contribute to beta cell dysfunction, leading to diabetes. By identifying and characterizing these factors we may be able to better monitor disease risk and progression, and develop therapeutics targeting these causal factors to delay, prevent, and cure diabetes. Dr. Prentice recently identified the Fabkin hormone complex as a novel target that is dysregulated in the prediabetic period in humans and pre-clinical models. She showed that Fabkin contributes to the development of overt diabetes in mice, and targeting Fabkin prevents and reverses Type 1 (T1D) and Type 2 Diabetes (T2D) in these models. For the Canada Research Chair in Diabetes Pathogenesis, Dr. Prentice will perform in-depth studies examining the role of Fabkin complex component NDPK in the development of T1D and T2D. She will elucidate roles in whole body metabolic homeostasis, evaluate sources and signaling pathways of Fabkin in beta cells, fat, and liver, and use cutting-edge techniques to determine mechanism of action, building toward the development of Fabkin-targeting therapeutics for the treatment and prevention of diabetes. Overall, Dr. Prentice's research will enhance our understanding of Fabkin as a therapeutic target and reshape our understanding of organ crosstalk in diabetes pathogenesis.

Canada Research Chairs - CIHR Funded - Tier 2


Romantic Imagination and the History of Methodology: Inductivism and Hypothetical Thinking in the Eighteenth-Century Newtonian Paradigm

This research project reinterprets Romantic modes of thought in terms of the methodological issues associated with inductive procedures in 18th century empirical science. For this purpose I traced how hypothetical reasoning, which emerged from the limitations of inductivism, historically developed into a “principle” of imagination and creativity in the Romantic era. By chiefly examining the texts of S.T. Coleridge, which cover multiple fields of knowledge such as literary criticism, philosophy, science, history, and medicine (physiology and pathology), I analyzed the procedures of argumentation and the formation of theories as found in Romantic critical discourse. I also clarified how these Romantic ways of thinking contributed to shaping paradigms that supported various fields of thought that newly emerged in the early 19th century.

Japan Society for the Promotion of Science

Osaka Medical and Pharmaceutical University


Chronic Pain Management in Veterans with Co-occurring Substance Use Disorders

Approximately 500,000 Veterans receiving care through VHA have one or more substance use disorders (SUDs), and a significant proportion of these Veterans experience chronic pain. Unfortunately, pain treatment as usual may ineffectively manage pain for these Veterans, and undertreated pain is associated with early dropout from specialized SUD treatment, continued substance abuse and relapse following completion of specialty SUD treatment, and poor long-term psychosocial functioning. Managing pain in Veterans with SUDs is critically important, yet little is known about current pain treatment practices within VA for Veterans with co- occurring chronic pain and SUDs, nor treatments that effectively manage pain and reduce substance abuse in this population. The proposed research addresses this current knowledge gap.


Regulation of hepatic cytochrome P450 expression and activity in a rat pain model

Cytochromes P450 (CYPs) comprise a large family of hemoproteins, and are believed to play important roles in biotransformation of xenobiotics. The expression of CYPs is altered by numerous drugs and environmental chemicals, as well as during the operation of host defence mechanisms. It is fairly well accepted that for most of the enzyme forms, there is a loss in the specific mRNA and subsequent protein synthesis during inflammation and infection. Regulation of various CYPs involves protein intermediates, believed to be transcription factors belonging to the nuclear receptor superfamily. An exciting challenge for the future will be to understand the more general aspects of CYPs and nuclear receptor biology, as related to the design of novel therapeutics. In drug development, the set up of an effective strategy for testing new analgesics is dependant on the pre-clinical availability of well-documented pain-models that will reproduce conditions in man. The aim of this project is to elucidate the molecular mechanisms underlying the complex signalling network involving inflammation-regulated nuclear receptors and CYPs, to better our knowledge of variability in drug metabolism, for the ultimate goal of designing safer medications.


The Conformational Dynamics of Two-Way DNA Junctions: A common first step in aberrant DNA recognition?

study of the conformational dynamics of aberrant DNAs. Experimental data from single-molecule FRET, fluorescent lifetimes spectroscopy, and other biophysical techniques, will be combined with molecular dynamic simulations (with Kresten Lindorff-Larsen in Copenhagen) to produce the most detailed view of aberrant DNA conformational dynamics to date. This multidisciplinary approach will help us understand the first step in aberrant DNA detection.
The successful student will join a vibrant and world-leading research grouping within the Krebs Institute for Mechanistic Biology and Imagine: Imaging Life, developing skills in cutting-edge single-molecule and ultrafast spectroscopy, and molecular modelling, with opportunities for industrial engagement as the project progresses.

Biotechnology and Biological Sciences Research Council


Narrative: Dr. Joshua Bauer's cancer-related projects within the Vanderbilt High-Throughput Screening (HTS) Facility are focused on three areas: 1) compound library screening and other HTS drug screening, 2) functional genomic (siRNA) library screening, and 3) high-content screening (HCS) and analysis. His integral role and success stems from his ability to collaborate, design and perform screens, and intellectually contribute to projects, grant proposals, and manuscripts. The blend of his skills, expertise, and knowledge provide a unique, indispensable role within the Vanderbilt cancer research program to mend cancer research, chemical biology, genomics, drug discovery, and translational drug investigation.


Synthesis and Assembly of Flagellar Proteins


CHARACTERISTICS OF HERBAGE GRASS ECOTYPES COLLECTED AT ALPINE REGIONS IN NORTH - EASTERN JAPAN AND IN SOUTHERN GERMANY.

To investigate genetic resources suitable for Kitakami highland, characteristics of herbage grass ecotypes collected at alpine regions in north-eastern Japan and in southern Germany were evaluated at an experiment field (970m a.s.1.) near Morioka from 1992 to 1995. Investigated characters were general agricultural characters, digestibility, morphological characters, mineral content, and mineral release rates from cross section of leaves.Materials were perennial ryegrass, orchardgrass, tall fescue and timothy. For perennial ryegrass, 13 Japanese ecotypes, 2 Japanese cultivars, 9 German ecotypes, and 3 German cultivars. For orchardgrass, 11 Japanese ecotypes, and one of each German ecotype and cultivar, six Japanese ecotypes for tall fescue and 8 German ecotypes for timothy were used for this study.For perennial ryegrass, German ecotypes were better in winter hardiness, earlier in heading date, and more in number of heads than the other groups. Japanese ecotypes were larger than German ecotypes, but characters related with digestibility were not differ. German ecotypes would be one of promising genetic resources suitable for Kitakami highland.Cross sections of leaves of three grass species were soaked in water for 5 minutes to 12 hours. Mineral release analyzed with Energy Dispersive X-ray analyzer. Release percentage was highest in K.It was medium in CI and Ca, Low in S,P and Mg, and lowest in Si. Varietal differences in the water-solubility of minerals were small.

Grant-in-Aid for General Scientific Research (C)