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关键词： 桥梁工程   车-桥耦合系统   数值模拟   随机车流   伸缩缝  

摘要： 大跨桥梁上的车流重力动态分布和作用在变形主梁上的时变纵向力,决定梁端伸缩缝纵向变形,实现伸缩缝纵向变形分析,车-桥耦合系统是核心,实现车流重力分布和纵向力计算加载的车流微观行驶行为仿真及力学化的理论方法是关键.首先,从元胞尺寸和行驶规则2个角度对仿真方法进行精细:把实测车型典型轴距对标当前市场车型,确定各车型车辆前、后悬长并纳入车长考虑,基于多车型的车长公约数综合确定元胞尺寸,使得各车型的车长在仿真交通流中得到差异且全面的元胞表达,奠定精细仿真元胞基础;在车间距基础上,把车速差纳入考虑,丰富车辆微观行驶决策因素,并设定多级变速和变道优先权,从宏观规则和处置细节上对车流行驶微观行为进行精细化.其次考虑到车速是车辆行驶行为的直观表现,采用动量定理实现车辆变速行为到纵向力(力矩)的转换;把纵向力(力矩)均分加载在车辆占据的各元胞中心,实现车辆出、入桥力学过程的适度精细模拟;匹配车辆行驶行为,调整车流判断流程和加载识别部分,完善微观车流-桥梁分析系统.最后,以一座斜拉桥为工程背景,对不同密度组成的车流作用下伸缩缝的纵向变形进行分析.结果 表明:①与单向车流相比,计算密度下双向车流的总体纵向力在均值和极值上的加强度的极值分别为1.6和1.5,即双向车流有相互作用,总体表现为抵消;②车流重力因素产生的主梁纵向变形较为稳定,伸缩缝纵向响应时程曲线围绕重力产生的伸缩缝纵向变形均值上下波动,波动幅度总体趋势受密度控制,在正、负(方向)上的极值和均值随车流密度增大大体均呈增大趋势,波动局部受上下行密度差控制,当双向车流密度之和一定时,双向车流的密度差越大,极值和均值就越大;③伸缩缝纵向位移服从正态分布,伸缩缝累积行程随车流总密度、上下行密度差增大呈增大趋势,车流密度、密度差越大,伸缩缝磨损范围越大,磨损程度越严重.

关键词： Tetravalent dengue DNA vaccine   Tetravalent dengue inactivated vaccine   Tetravalent dengue live-attenuated vaccine   Prime-boost   Non-human primates   VIRUS-VACCINE   PHASE-II   IMMUNOGENICITY   SAFETY   BLOOD   PATHOGENESIS   INFECTION  

摘要： We previously reported the efficacy of prime-boost vaccination using three tetravalent (T) dengue vaccines, DNA (TDNA), purified inactivated vaccine (TPIV), and live attenuated vaccine (TLAV). We demonstrated that the TPIV/TLAV prime-boost vaccination yielded the highest and most durable neutralizing antibodies and 100% protection to all 4 serotypes of dengue virus in rhesus macaques. This study compares gene transcription, T and B cell responses elicited by these prime-boost combinations in rhesus macaques. This study shows that the TLAV vaccine increased the expression of the innate immune genes, DDX58 and TLR7, IL1A, IL1B, TNF, CXCL8, CXCL10, IRF1, IRF7, and IFNB, more robustly as compared to TDNA and TPIV vaccines. Overall, two doses of TDNA and one dose of TLAV efficiently elicited a T cell IFN gamma response to PrM/E with a comparable magnitude. Compared to TDNA vaccine, the TLAV vaccine elicited additional IFN gamma response to C, NS1, NS3, and NS5. The TPIV vaccine alone produced poor IFNc response; however, the TLAV significantly boosted its IFN gamma response. The T cell response repertoire associated with TPIV/TLAV prime-boost was to both the structural C/PrM/E and NS proteins, and the T cells were multifunctional as the CD4(+) T cells produced IFNc, TNF alpha, and IL2 and the CD8(+) cells produced TNF alpha and IFN gamma. Opposite to the pattern of CMI, the TPIV vaccine alone elicited the highest B-Mem compared to the other two vaccines, which continuously remained as the highest after boosting. In summary, the TDNA and TLAV vaccines elicited a strong T cell response whereas the TPIV vaccine elicited a superior B-Mem. The T cell response of the TPIV vaccine was significantly boosted by the TLAV vaccine. The elevated T cell response may have provided T cell help for a sustained antibody response for TPIV/TLAV vaccines, which is required for a protective immunity against a live virus challenge. Published by Elsevier Ltd.

关键词： IN-VIVO   CUTANEOUS LEISHMANIASIS   VISCERAL LEISHMANIASIS   INTERFERON-GAMMA   INFECTION   SKIN   TUBERCULOSIS   RESPONSES   REVEALS   PROMASTIGOTES  

摘要： Nitric oxide (NO) is an important antimicrobial effector but also prevents unnecessary tissue damage by shutting down the recruitment of monocyte-derived phagocytes. Intracellular pathogens such as Leishmania major can hijack these cells as a niche for replication. Thus, NO might exert containment by restricting the availability of the cellular niche required for efficient pathogen proliferation. However, such indirect modes of action remain to be established. By combining mathematical modeling with intravital 2-photon biosensors of pathogen viability and proliferation, we show that low L. major proliferation results not from direct NO impact on the pathogen but from reduced availability of proliferation-permissive host cells. Although inhibiting NO production increases recruitment of these cells, and thus pathogen proliferation, blocking cell recruitment uncouples the NO effect from pathogen proliferation. Therefore, NO fulfills two distinct functions for L. major containment: permitting direct killing and restricting the supply of proliferation-permissive host cells.

摘要： Background : Standard of care (SOC) for second-line (2L) therapy (tx) of relapsed/refractory aggressive B-cell non-Hodgkin lymphomas (R/R aNHL) includes platinum-based chemotherapy (PCT) followed by autologous hematopoietic cell transplantation (aHCT) in responders. Outcomes are poor for patients (pts) with R/R aNHL who experience progression during or within 12 months (mo) of 1L tx. Tisagenlecleucel (tisa-cel) is an autologous chimeric antigen receptor (CAR) T-cell tx targeting CD19 approved for pts with large B-cell lymphoma (LBCL; US) and diffuse LBCL (non-US) after ≥2 lines of tx. BELINDA (NCT03570892) is a Phase III, randomized, global (18 countries) study of tisa-cel vs SOC as 2L tx for R/R aNHL. Methods : Adults with confirmed R/R aNHL within 12 mo after 1L chemo-immunotherapy were eligible. All pts underwent leukapheresis for tisa-cel production and were randomized 1:1 to receive tisa-cel (Arm A) or SOC (Arm B) and stratified by 1L duration of response, International Prognostic Index (IPI), and geographic region. Arm A received optional bridging tx (investigator choice of protocol-defined PCT regimens) followed by lymphodepletion (LD; generally, fludarabine 25 mg/m 2 /day [d] + cyclophosphamide 250 mg/m 2 /d for 3 d) and followed by a single tisa-cel infusion (0.6-6×10 8 CAR-T cells). Arm B received investigator choice of PCT regimen followed by aHCT in responders or a second PCT in nonresponders. Disease assessments were performed at 6 and 12 weeks (wk), then planned every 3 mo for year (y) 1 and every 6 mo for y 2. The primary endpoint was event-free survival (EFS), defined as time from randomization to stable disease (SD) or progressive disease (PD) at or after wk 12 assessment or death at any time. SD/PD at wk 6 was not considered an event on either Arm. Arm A's wk 6 assessment evaluated disease burden before tisa-cel infusion and after bridging if administered. Arm B's wk 6 assessment determined if response was sufficient for aHCT or if a second PCT reg

关键词： 道路桥梁   桥梁工程   伸缩缝技术  

摘要： 为有效避免后续道路桥梁出现裂缝的情况,对伸缩缝施工技术进行应用。通过道路桥梁工程中伸缩缝技术应用策略探究,并以实际工程建设进行应用和验证,为后期道路桥梁工程安全、平稳的使用,增强施工技术的准确性,确保整体道路桥梁工程的美观性提供可靠依据。

关键词： 道路桥梁工程   伸缩缝   施工技术   质量控制  

摘要： 随着社会经济的飞速发展,建筑行业为了适应当前经济发展需求,也呈现出了快速的发展态势。在我国的市政道路工程当中,高速公路的建设是公路建设的重中之重。我国的人均汽车保有量逐年上升,车流量越来越大,车速越来越快,在一些良田、保护区、山区、丘陵等地区需要架设高速公路桥,在桥梁的架设过程中,伸缩缝是施工技术的重要组成部分。伸缩缝施工质量是保障桥梁质量、路面平整度及行车安全的核心之一。许多技术人员对桥梁工程伸缩缝施工技术进行了研究,在实际的施工当中不断发现问题,并进行总结,寻找到了一套比较完善的伸缩缝施工技术和施工质量控制方法。在桥梁工程伸缩缝施工当中,由于受到外界环境的影响,如果处理不好这些影响因素,会导致桥梁建设后质量不达标等问题,严重的可能会在桥梁使用过程中出现塌陷等情况,严重威胁行车安全,所以,桥梁项目伸缩缝作业人员一定要利用科学的、合理的作业质量控制技术来管理伸缩缝的作业质量。