课程文献中心 更多>>

关键词： glycosyltransferase   mannosyltransferase   protein structure   molecular dynamics   mannan   cell wall   Aspergillus   CATALYTIC MECHANISM   FORCE-FIELD   SIDE-CHAIN   ALPHA-1,2-MANNOSYLTRANSFERASE   KRE2P/MNT1P   MANNOSYLTRANSFERASE   GLYCOSYLATION   KTR1P  

摘要： Fungal cell walls and their biosynthetic enzymes are potential targets for novel antifungal agents. Recently, two mannosyltransferases, namely core-mannan synthases A (CmsA/Ktr4) and B (CmsB/Ktr7), were found to play roles in the core-mannan biosynthesis of fungal-type galactomannan. CmsA/Ktr4 is an alpha-(1 -> 2)-mannosyltransferase responsible for alpha-(1 -> 2)-mannan biosynthesis in fungal-type galactomannan, which covers the cell surface of Aspergillus fumigatus. Strains with disrupted cmsA/ktr4 have been shown to exhibit strongly suppressed hyphal elongation and conidiation alongside reduced virulence in a mouse model of invasive aspergillosis, indicating that CmsA/Ktr4 is a potential novel antifungal candidate. In this study we present the 3D structures of the soluble catalytic domain of CmsA/Ktr4, as determined by X-ray crystallography at a resolution of 1.95 angstrom, as well as the enzyme and Mn2+/GDP complex to 1.90 angstrom resolution. The CmsA/Ktr4 protein not only contains a highly conserved binding pocket for the donor substrate, GDP-mannose, but also has a unique broad cleft structure formed by its N- and C-terminal regions and is expected to recognize the acceptor substrate, a mannan chain. Based on these crystal structures, we also present a 3D structural model of the enzyme-substrate complex generated using docking and molecular dynamics simulations with alpha-Man-(1 -> 6)-alpha-Man-(1 -> 2)-alpha-Man-OMe as the model structure for the acceptor substrate. This predicted enzyme-substrate complex structure is also supported by findings from single amino acid substitution CmsA/Ktr4 mutants expressed in Delta cmsA/ktr4 A. fumigatus cells. Taken together, these results provide basic information for developing specific alpha-mannan biosynthesis inhibitors for use as pharmaceuticals and/or pesticides.

关键词： Trigeneation   Portable   PVT   PV   PEMFC   STEADY-STATE   PERFORMANCE   ENERGY   POWER  

摘要： Developing micro-trigeneration systems is an important step in military applications. Therefore, suggesting new portable trigeneration systems that use several energy sources is necessary. The importance of the issue is enhanced when renewable energy sources are used in suggested systems for places with no accessibility to energy sources. In this paper, different useful micro-personal trigenertion systems are proposed based on photovoltaic/thermal (PVT) and combination of photovoltaic (PV) with proton exchange membrane fuel cell (PEMFC). The proposed systems are designed to provide all or a part of personal demand loads by photovoltaic phenomena. Using different energy sources such as solar and hydrogen electrochemical energies in the proposed systems increases the flexibility and reliability of the system. The trigeneration performance of suggested cycles is simulated in the engineering equation solver software (EES) and the results based on different prime movers are compared with the system based on ultra-micro gas turbine (UMGT), which was studied in the previous work under extremely cold/hot weather. Although utilizing the PV module and PVT collector improves the performance of the system, it increases its weight as well, which is not suitable in portable applications. Therefore, the size of elements must be selected carefully. Results showed that the system based on PVT generated more power in summer so that the maximum of 105 and 17 W electrical power were generated with overall efficiency of 14% and 9% in summer and winter at maximum solar irradiance respectively. In addiotion, the most efficient system was the system based on UMGT in which the maximum overall efficiency was 21% and 28% in summer and winter respectively. The effects of the water mass flow rate of PVT on power and overall efficiency were investigated too. We found that increasing in mass flow rate increases the power and overall efficiency slightly about 16% and 15% in summer and about 33% an

关键词： NEWLY-DIAGNOSED GLIOBLASTOMA   RANDOMIZED PHASE-III   LYMPHOPROLIFERATIVE DISEASE   BEVACIZUMAB   CYTOMEGALOVIRUS   TEMOZOLOMIDE   THERAPY   EXPRESSION   RADIOTHERAPY   SURVIVAL  

摘要： BACKGROUND. The recent failure of checkpoint-blockade therapies for glioblastoma multiforme (GBM) in late-phase clinical trials has directed interest toward adoptive cellular therapies (ACTs). In this open-label, first-in-human trial, we have assessed the safety and therapeutic potential of cytomegalovirus-specific (CMV-specific) ACT in an adjuvant setting for patients with primary GBM, with an ultimate goal to prevent or delay recurrence and prolong overall survival. METHODS. Twenty-eight patients with primary GBM were recruited to this prospective study, 25 of whom were treated with in vitro-expanded autologous CMV-specific T cells. Participants were monitored for safety, progression-free survival, overall survival (OS), and immune reconstitution. RESULTS. No participants showed evidence of ACT-related toxicities. Of 25 evaluable participants, 10 were alive at the completion of follow-up, while 5 were disease free. Reconstitution of CMV-specific T cell immunity was evident and CMVspecific ACT may trigger a bystander effect leading to additional T cell responses to nonviral tumor-associated antigens through epitope spreading. Long-term follow-up of participants treated before recurrence showed significantly improved OS when compared with those who progressed before ACT (median 23 months, range 7-65 vs. median 14 months, range 5-19; P = 0.018). Gene expression analysis of the ACT products indicated that a favorable T cell gene signature was associated with improved long-term survival. CONCLUSION. Data presented in this study demonstratethat CMV-specific ACT can be safely used as an adjuvant therapy for primary GBM and, if offered before recurrence, this therapy may improve OS of GBM patients.

关键词： 高速公路   桥梁伸缩缝   病害分析   快速维修  

摘要： 截至2019年底,我国高速公路总里程接近15万km,1998~2016年,我国高速公路年平均通车里程为6642km,平均增速20%,为全国180亿人次的出行和130亿t货物流通提供基础设施。但同时,高速公路桥梁施工也存在一些容易造成质量事故的因素,存在制约着高速公路质量管控的问题,分析桥梁伸缩病害原因,给出解决办法,希望能给相关人员提供借鉴。

关键词： 市政   道路桥梁   伸缩缝   施工  

摘要： 随着社会地不断发展和进步,工程建设的施工技术也在不断的提升,而作为与民生息息相关的市政工程基础设施建设,更是在工程建设中占据了相当重要的地位。其中,道路桥梁工程是最为常见的市政工程之一,在市政工程施工环节,占据了相当重要的地位,因此道路桥梁的施工质量很大程度上决定了该市政工程的使用寿命,而伸缩缝施工就是其中一个重点内容,其施工质量将会对路桥质量安全和行车体验产生直接影响,现场施工技术人员应对这部分施工内容引起重视并有效解决相关问题才能保证市政工程更加稳定运行。本文主要结合桥梁伸缩缝伸缩装置在施工过程中的研究,探讨市政道路桥梁施工中伸缩缝应用情况及施工要点。

关键词： 设计说明   私人空间   和谐融合   婚庆   工作室   公共空间   功能分区  

摘要： 设计说明:SOHO模式下的婚庆工作室,商住两用。将办公与家居融为一体,现代简约的设计风格让不同的功能分区和谐融合。整个设计以灰色为基调,墙面以白色和暖色为主,便于展示婚纱,同时让客户更易放松下来,达到私人空间与公共空间的自然转换。