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关键词： PEPTIDES   ADENOSINE triphosphate   CHEMICAL inhibitors   LIGANDS (Biochemistry)   CHEMICAL reactions  

摘要： ERK2 primarily recognizes substrates through two recruitment sites, which lie outside the active site cleft of the kinase. These recruitment sites bind modular-docking sequences called docking sites and are potentially attractive sites for the development of non-ATP competitive inhibitors. The D-recruitment site (DRS) and the F-recruitment site (FRS) bind D-sites and F-sites, respectively. For example, peptides that target the FRS have been proposed to inhibit all ERK2 activity (Galanis, A., Yang, S. H., and Sharrocks, A. D. (2001) J. Biol. Chem. 276, 965-973);however, it has not been established whether this inhibition is steric or allosteric in origin. To facilitate inhibitor design and to examine potential coupling of recruitment sites to other ligand recognition sites within ERK2, energetic coupling within ERK2 was investigated using two new modular peptide substrates for ERK2. Modeling shows that one peptide (Sub-D) recognizes the DRS, while the other peptide (Sub-F) binds the FRS. A steady-state kinetic analysis reveals little evidence of thermodynamic linkage between the peptide substrate and ATP. Both peptides are phosphorylated through a random-order sequential mechanism with a k(cat)/K-m comparable to Ets-1, a bona fide ERK2 substrate. Occupancy of the FRS with a peptide containing a modular docking sequence has no effect on the intrinsic ability of ERK2 to phosphorylate Sub-D. Occupancy of the DRS with a peptide containing a modular docking sequence has a slight effect (1.3 +/- 0.1-fold increase in k(cat)) on the intrinsic ability of ERK2 to phosphorylate Sub-F. These data suggest that while docking interactions at the DRS and the FRS are energetically uncoupled, the DRS can exhibit weak communication to the active site. In addition, they suggest that peptides bound to the FRS inhibit the phosphorylation of protein substrates through a steric mechanism. The modeling and kinetic data suggest that the recruitment of ERK2 to cellular locations via its DRS ma

关键词： 细菌学   医院   感染  

摘要： 医院感染又称医院内感染或医院内获得性感染，其伴随医院的出现而发生，感染率有迅速增长之势，不仅增加了患者的发病和痛苦死亡率上升，而且住院时间明显延长，加重了患者的经济负担。因此医院感染成为一个广大医务工作者当前严峻的问题。

关键词： 质量提升   检验检疫协会   作用  

摘要： 检验检疫机构是国家进出口质量监管机构,对进出口产品质量负有监管责任,在履行质量监管责任过程中,如何借助社会力量,以解决在某些领域对产品质量监管缺位问题值得探究。检验检疫协会作为社会力量的一部分,依托检验检疫机构的技术优势,发挥行业协会组织、引导、协调、建议等职能,拓展检企沟通渠道,在实现产品质量提升过程中作用越来越显著。

关键词： 医学检验   临床   地位及作用  

摘要： 医学检验是现代实验室科学技术与临床的结合，是一门多学科交叉，相互渗透的新兴学科。近年来，随着科学和医疗卫生事业的发展，人们对疾病的认识越来越深入。为了准确诊断疾病，为临床治疗提供科学依据，检验工作者必须做出更准确的检验结果协助临床诊断和鉴别诊断各种疾病。医学检验范同十分广泛，其中有临床生化检验、临床微生物检验、免疫学、寄生虫学、形态学、血清学检验。

关键词： child welfare   children   community intervention   evidence-based practice   intervention   quantitative  

摘要： Objectives: The purpose of this study was to evaluate Parent-Child Interaction Therapy (PCIT) deployed in a community setting comparing in-home with the standard office-based intervention. Child behavior, parent stress, parent functioning, and attrition were examined. Methods: Using a quasi-experimental design, standardized measures at three time points were collected from parent-child dyads (n=120) with thirty-seven families completing treatment. Results: Growth modeling analyses indicate significant improvements in child and parent outcomes in both treatment settings with more rapid improvements in parent outcomes within office-based treatment. Attrition was predicted by income and parent functioning. Conclusion: PCIT delivered in the community can produce measureable improvements. In-home PCIT is a feasible option but future research should consider benefits and costs. Treatment completion remains a challenge.

关键词： Partial Little Square   Data Type   Random Forest   Molecular Data   Classification Algorithm  

摘要： Background: Combining clinical and molecular data types may potentially improve prediction accuracy of a classifier. However, currently there is a shortage of effective and efficient statistical and bioinformatic tools for true integrative data analysis. Existing integrative classifiers have two main disadvantages: First, coarse combination may lead to subtle contributions of one data type to be overshadowed by more obvious contributions of the other. Second, the need to measure both data types for all patients may be both unpractical and (cost) inefficient. Results: We introduce a novel classification method, a stepwise classifier, which takes advantage of the distinct classification power of clinical data and high-dimensional molecular data. We apply classification algorithms to two data types independently, starting with the traditional clinical risk factors. We only turn to relatively expensive molecular data when the uncertainty of prediction result from clinical data exceeds a predefined limit. Experimental results show that our approach is adaptive: the proportion of samples that needs to be re-classified using molecular data depends on how much we expect the predictive accuracy to increase when re-classifying those samples. Conclusions: Our method renders a more cost-efficient classifier that is at least as good, and sometimes better, than one based on clinical or molecular data alone. Hence our approach is not just a classifier that minimizes a particular loss function. Instead, it aims to be cost-efficient by avoiding molecular tests for a potentially large subgroup of individuals;moreover, for these individuals a test result would be quickly available, which may lead to reduced waiting times (for diagnosis) and hence lower the patients distress. Stepwise classification is implemented in R-package stepwiseCM and available at the Bioconductor website.

关键词： SUSTAINABLE architecture   SUSTAINABLE building design & construction   CONSTRUCTION contracts  

摘要： The article reports on the plan of the American Institute of Architects (AIA) to issue green model contract forms in order to minimize the exposure of sustainable projects to legal issues in the U.S. Institute associate counsel Joshua Balance explains that the goal of the forms is to ensure the correct definition of the roles and responsibilities. The forms are based on contract agreements between owner and architect and between owner and contractor.

关键词： 3D lithography   cell–cell interactions   hydrogels   neuro–muscular junctions   tissue engineering  

摘要： A spatially organized three-dimensional (3D) co-culture of multiple cell types is required to recapitulate cellular interactions and microenvironments in complex tissues. Although there are limited reports for 3D patterning of cells and materials, approaches to examine functional interactions of 3D spatially patterned multiple cell types are lacking entirely. This is mostly due to difficulties in controlling the physical arrangement of cells in a 3D matrix and the physical properties of the cell-encapsulating matrix, while keeping the cells alive and functional for extended periods of time. In this study, an automated maskless fabrication technique is combined with a tunable polymer blend to spatially organize primary hippocampus neurons (HNs) and skeletal muscle myoblast cells (MCs) in a 3D hydrogel matrix with tunable mechanical and degradation properties. The spatial organization of these multiple cell types revealed that the presence of MCs resulted in increased cholinergic functionality of the HNs, as quantified by their choline acetyltransferase activity. The presence of a factor alone is not sufficient, but its spatiotemporal control is necessary;a condition that is possibly true for many cellular interactions. Therefore, the system described here offers a different approach to examine such previously unknown interactions. The approach proposed in this study can be used to examine interactions between many different cell types and shift the 3D fabrication paradigm to a next level, which is to fabricate tissues that are not only viable but also functional.

关键词： 医学检验   感染管理   制度规程   防护处理  

摘要： 医院感染与医疗质量和医疗安全密切相关,直接影响到患者的安全和医务人员的健康。本文针对当前医院检验科在感染管理工作方面存在的一些问题,提出了相应的对策和意见。

关键词： 生化检验   肾上腺皮质疾病   应用  

摘要： 目的探讨生化检验在肾上腺皮质疾病诊断中的作用。方法回顾性分析2009年4月至2011年4月因肾上腺皮质疾病入住我院的64位患者的临床资料,按所采取检验方法的不同分为生化检验组和常规检验组。其中生化检验组38例,常规检验组26例。结果生化检验组检验有效36例,检验无效2例,有效率为94.7%;常规检验组检验有效19例,检验无效7例,有效率73.1%。结论生化检验较常规检验在肾上腺皮质疾病诊断中的作用显著,可作为肾上腺皮质疾病的例行检查。