本研究提出一种相互匹配的试验与数值综合模拟技术，用以探索沥青混合料的细观断裂行为规律。首先采用切口小梁三点弯曲试验模拟沥青混合料的断裂过程，并通过数字图像相关技术对其细观裂缝的启裂与扩展过程进行观测，测定沥青混合料的细观断裂参数，分析其细观断裂判据；进而采用简单性能试验及劈裂试验测定沥青砂浆与玄武岩集料的力学参数及断裂参数，并通过数字图像处理技术分析沥青混合料截面图像，生成兼顾计算效率与精度的沥青混合料数字试件；在此基础上采用扩展有限元技术进行沥青混合料虚拟切口小梁三点弯曲试验，模拟其细观断裂过程，探索细观裂缝启裂判据、细观裂缝扩展路径等规律。最后利用试验结果对数值模型的有效性与数值模拟结果的正确性进行验证。研究结果可为沥青混合料的细观断裂机理研究提供一个有效的方法，同时也为沥青混凝土路面的抗裂设计及养护修复技术研究提供理论支持。

肾小球硬化是CKD进展至ESRD的主要病理基础。研究发现,GMCs凋亡是肾小球硬化的主要病理特征，且Notch信号通路参与细胞凋亡的发生过程。益肾散结复方可防治肾小球硬化，但配伍机制尚待研究。因此，本课题展开研究:①体内实验：建立阿霉素肾病大鼠模型，将其分为正常组、盐酸贝那普利组、温肾益精化瘀组、滋阴益肾化瘀组、益气化瘀组及益肾散结复方组，药物干预后检测药效学指标;RT-PCR、Western-Blot测定肾组织Notch信号通路相关蛋白的表达；免疫组化验证相关蛋白表达；电镜观察形态学改变;②体外实验：培养大鼠肾系膜细胞，分组同上，药物干预后,CCK-8法检测增殖活力；流式细胞术检测凋亡和周期变化;Western-Blot、ELISA、RT-PCR测定其Notch信号通路相关蛋白表达情况；电镜观察形态学改变。从细胞分子水平探讨益肾散结复方防治肾小球硬化的作用靶点及机制，揭示配伍的科学内涵。

DESCRIPTION (provided by applicant): Osteocytes (OCY) are intrinsically three-dimensional (3D), mature bone cells encased in 3D mineralized extracellular bone matrix. Recent studies indicate the critical roles of osteocytes in detecting mechanical signals and maintaining skeleton integrity. These roles have significant clinical implications, such as in the etiology of osteoporosis or new pharmaceutical targets for osteoporosis treatment. A novel 3D trabecular bone explant co-culture model for osteocyte-osteoblast mechanobiology in this proposal allows for live osteocytes to be surrounded by their native extracellular matrix environment and to interconnect with osteoblasts (OB) through intercellular processes in the canaliculi channels. We propose to use this novel 3D trabecular bone co-culture model to test a central scientific hypothesis that that dynamic deformational loading induces OCYs to send anabolic signals to OBs to promote bone formation through intraceluar calcium [Ca2+]i oscillations in osteocytic network, followed by prostaglandin E2 (PGE2) production/secretion via gap junctions/hemi-channels to OBs. We will test the following working hypotheses: Hypothesis H1: PGE2 production, changes in bone formation, and elastic modulus of 3D bovine trabecular bone explants with seeded primary bovine OBs depend on calmodulin kinase (CaMK) dependent Ca2+ oscillations in OCYs. Hypothesis H2: PGE2 production, changes in bone formation, and elastic modulus of 3D bovine trabecular bone explants with seeded primary bovine OBs depend on the gap junctions/hemi-channels connexin 43 (Cx43) in OCYs. Hypothesis H3: Bone formation response of OBs seeded in 3D trabecular bone explants under dynamic deformational loading and changes in elastic modulus of trabecular bone depend on PGE2 pathway. With this new co-culture system of trabecular bone explants, the interaction between osteocytes and osteoblasts under mechanical loading can be investigated in vitro under conditions that are more physiologically relevant than previously possible: (1) both osteocytes and osteoblasts are included and positioned in their native 3D trabecular bone environment when subjected to dynamic deformational loading; (2) functional bone formation and elastic modulus of trabecular bone will be assessed in vitro, linking important factors in osteocyte-osteoblast mechanotransduction to bone functions; (3) selectively manipulating biochemical pathways in OCYs and OBs independently with sophisticated molecular biology technique, which cannot be achieved in vivo, and (4) micromechanical environments surrounding osteocytes and/or osteoblasts will be quantified, respectively, using specimen specific finite element models. New insights will be gained regarding cellular and molecular mechanisms of bone cell mechanotransduction and will contribute to our general understanding of the etiology of osteoporosis, and may lead to therapeutic interventions aimed at the mitigation or treatment of osteoporosis.

Project Summary Stroke is the number 1 cause of disability in the United States and a global public health problem.Globally, approximately 15 million people suffer a stroke each year,leading to 5 million deaths and another 5 million patients who suffer permanent disability from their stroke.Strokes that are caused by blockage of large blood vessels supplying blood to the brain are typically the most disabling.Over the last 5 years,there have been major breakthroughs in acute stroke therapy for this type of stroke.In 2015,multiple trials demonstrated a profound benefit from endovascular stroke therapy for patients with a large vessel ischemic stroke who present in the early time-window(within 6 hours after symptom onset).This success was followed by the DEFUSE 3 and DAWN trials showing a very strong benefit from endovascular therapy in the delayed time-window(6-24 hours after symptom onset).These therapies have now become standard of care at specialty hospitals (comprehensive stroke centers)across the country.Despite this new highly effective therapy,stroke-related disability continues to be substantial for patients with large-vessel occlusions,because of brain damage that occurs in the time-period before patients receive endovascular therapy that restores blood flow to the brain.The time period before blood flow is restored can be long(several hours)especially if patients need to be transferred from a community hospital that does not have the capability to provide endovascular therapy to a comprehensive stroke center that does.Because of this delay,significant brain damage can occur between the time that a patient initially presents to a hospital and the time that blood flow is restored.To address this problem,we need to conduct clinical trials of therapies that protect the brain in the crucial time-period before blood flow is restored. In order to conduct such trials,we first need tools to identify patients who are most likely to benefit from treatments that protect the brain and tools that can be used to determine if the treatments are effective.The overall aim of this project is to develop these tools.We will achieve this aim using both an existing imaging dataset and using new data that we will obtain from patients who are being transferred from a community hospital to a comprehensive stroke center for endovascular therapy.To identify patients who will likely benefit from treatments that protect the brain,we will develop a CT-based tool that visualizes how much brain damage a patient is likely to sustain during transport.To be able to determine if a treatment is effective at protecting the brain,we will develop a CT-based tool that can accurately measure the amount of brain damage(infarct volume) that is already present prior to transport.

Цель проекта-реконструкция истории экосистем центра Европейской России в суббореальном и субатлантическом периодах голоцена(от 5000 л.н.до современности)и оценка вклада биотических и антропогенных факторов в динамику экосистем. В результате выполнения проекта будет разработана и апробирована оригинальная методология реконструкции истории лесных ландшафтов,основанная на экосистемном подходе и направленная на выявление прямых факторов и механизмов экосистемных смен.Оригинальность и новизна проекта заключается в комплексном использовании методов почвенной морфологии,педоантракологии и палеоботаники. Исследования будут проводиться на модельных участках,расположенных в ландшафтах различных типов в подзонах хвойно-широколиственных и широколиственных лесов.Участки расположены в в различных регионах центра Европейской России и имеют разную историю хозяйственного освоения. На основе анализа результатов почвенно-морфологических,педоантракологических,палинологических исследований,анализа свойств торфяных залежей будет выполнена реконструкция событий в истории экосистем модельных участков на территориях ряда областей центра Европейской России,выявлены факторы экосистемных смен в лесных ландшафтах.Радиоуглеродное датирование углей и органического вещества дневных почв и торфяных отложений позволит синхронизировать информацию,полученную разными методами.Будут построены хроноряды долговременной динамики экосистем и их компонентов на локальном и региональном уровнях.Впервые на основе сопряженного анализа дневных почв и торфяных залежей будет дана оценка вклада биотических и антропогенных факторов в динамику экосистем на разных пространственных уровнях для наиболее показательных временных срезов второй половины голоцена.

The aim of this study is to investigate rare variants associated with asthma by exome analysis using next generation sequencer. We performed exome analyses on 67 patients who were diagnosed with asthma. Control genotype/allele frequencies were obtained from Human Genetic Variation Database. In the genomic regions which were identified to be associated with asthma by genome-wide association studies, we found two missense variants (one in IL1RL1 and the other in GSDMB) to be possibly associated with asthma (P < 0.05). We also found several candidate rare variants to be associated with asthma.

In public spaces, not only human conversation and ordinary public address announcements but also warnings and evacuation information in an emergency must be clearly transmitted. To tackle this theme, comprehensive research is needed not only by building acoustics but also by speech science, electro-acoustics, signal-processing, cognitive psychology and so on. Then, five components which were 1：sound environment and acoustical transmission characteristics in public spaces, 2：electro-acoustic system, 3：speech synthesis, 4：sign-signal design, and 5：auditory perception and cognition were set, and an acoustic design system using auralization techniques combined with the five components was built.