Highly Sulfated Forms of Heparin Sulfate Are Involved in Japanese Encephalitis Virus Infection

AbstractJapanese encephalitis virus (JEV) infects a broad range of cell types in vitro, though little is known about the initial events of JEV infection. In the present study, we found that highly sulfated glycosaminoglycans (GAGs) are involved in infection of both neurovirulent (RP-9) and attenuated (RP-2ms) JEV strains. Competition experiments using highly sulfated GAGs, heparin and dextran sulfate, demonstrated an inhibition of JEV's attachment and subsequent infection of BHK-21 cells. Treatment of target cells by a potent sulfation inhibitor, sodium chlorate, greatly reduced viral binding ability as well as infection, suggesting a critical role of GAGs' sulfation status on the cellular surface in JEV infection. This phenomenon was confirmed by the manifestation of a distinct binding efficiency of JEV to the wild-type CHO cell line and its mutants with defects in GAG biosynthesis. We also demonstrated the binding of JEV particles and virus envelope glycoprotein to immobilized heparin beads. Furthermore, the addition of heparin suppressed the cytopathic effects induced by JEV infection in cultured cells. Our results establish that the highly sulfated form of GAGs on cell surfaces plays a determining role in the early stage of in vitro JEV infection

State Transportation Improvement Program for Federal Fiscal Years 2011-2014

OBJECTIVES:To develop and validate a Taiwanese version of the Health Enhancement Lifestyle Profile (HELP-T) for community-dwelling older Taiwanese adults (≥ 55 years). METHODS:The original Health Enhancement Lifestyle Profile (HELP) is a 56-item self-report questionnaire measuring various aspects of health-related lifestyles in older adults. The standard cultural-adaptation procedure was used for questionnaire translation and modification. A field test was conducted for culturally specific item selection, rating-scale analysis, and psychometric validation of the HELP-T in a sample of 274 community-dwelling older adults via classical test theory. RESULTS:The 59-item HELP-T is culturally adapted from the original 56-item HELP. The original 6-point rating scale was modified to a 3-point scale for easy use by Taiwanese older adults. The HELP-T had good internal consistency (Cronbach's alpha = 0.82). The test-retest reliability for the total score was high (0.92), and moderate to high (range: 0.57-0.92) for subscales. The construct validity was supported by the significant correlations between each subscale and the total score (Spearman's rho = 0.41-0.67, p < 0.0001) and by the ability of the scores to significantly discriminate between participants with different levels of self-rated health (p = 0.0001). CONCLUSIONS:The HELP-T is a suitable clinical tool for assessing and monitoring lifestyle risk factors, establishing client-centered lifestyle intervention goals, and determining the outcomes of lifestyle interventions

Studying China’s IT Services Industry: Generalizations, Particularities, and the Competitive Outlook

China’s IT Services industry has grown rapidly in the last decade. Chinese government has made it a priority to invest in the improvement of the capabilities of Chinese vendors, which helped vendors to expand and grow in local and global markets. Despite the fact that China is the second largest industrial economy, IS researchers are only now starting to pay serious attention to China’s IT Services industry. This panel is aimed at stimulating research in this area by debating two approaches: one approach that focuses on unique opportunities offered by this setting for developing insights generalizable to other settings and a second approach focused on generating theories that focus on the specifics of the Chinese context. Academic panelists, all of whom have conducted studies of China’s IT Services, will argue these different positions. They will be joined by an industry leader from IT services industry in China, who would talk about the future of the industry

Report on grade assessment situation of the 12 prevention and control center pilot in Sichuan Province

目的  了解疾病预防控制机构（简称疾控机构）能力建设、经费保障、运行管理等情况，探索全省疾控等级评审方法和程序。方法  组织专家按照统一的评审标准对12家试点单位在政策环境、基础条件、疾病预防控制、检验检测、健康危害相关因素、信息化建设等7大类38个指标167个参数进行现场评审。结果  机构得分最高是自贡市，考核内容得分率较低的是检验检测和健康危害因素监测与控制，创建过程中各级政府对疾控机构在人、财、物方面均有不同程度的投入，A类和B类项目开展率有所增加，制定了疾控机构三级两等的评审标准。结论  疾控机构等级评审是疾控机构标准化建设和发展的有力抓手，通过评审能发现短板、弥补不足，增强政府在卫生防病方面的主体责任意识。Objective: To understand the situation of ability construction, funds guarantee, operation management of disease control agency, trying to figure out assessment method and program for prevention and control center. Methods: According to the unified standard, evaluation experts were organized to evaluate 12 pilot units. The assessment include 7 categories, 38 indicators and 167 parameters:  the policy environment, basic conditions, disease prevention and control, inspection, health relative factors, information construction, etc. Results: Zigong scored highest in all instituions. Inspection and health hazards monitoring and control scored lower in all categories.  In the process of setting up, all levels of government have different input on personnel, property and goods to prevention and control center. The development rate of type A and type B project increased. The classification standards were produced. Conclusion: Grade assessment is important to construction and development standardization of disease control agency. The assessment can find the weakness, make up the deficiency, strengthen responsibility consciousness of the government

A novel pathway regulates memory and plasticity via SIRT1 and miR-134

The NAD-dependent deacetylase Sir2 was initially identified as a mediator of replicative lifespan in budding yeast and was subsequently shown to modulate longevity in worms and flies. Its mammalian homologue, SIRT1, seems to have evolved complex systemic roles in cardiac function, DNA repair and genomic stability. Recent studies suggest a functional relevance of SIRT1 in normal brain physiology and neurological disorders. However, it is unknown if SIRT1 has a role in higher-order brain functions. We report that SIRT1 modulates synaptic plasticity and memory formation via a microRNA-mediated mechanism. Activation of SIRT1 enhances, whereas its loss-of-function impairs, synaptic plasticity. Surprisingly, these effects were mediated via post-transcriptional regulation of cAMP response binding protein (CREB) expression by a brain-specific microRNA, miR-134. SIRT1 normally functions to limit expression of miR-134 via a repressor complex containing the transcription factor YY1, and unchecked miR-134 expression following SIRT1 deficiency results in the downregulated expression of CREB and brain-derived neurotrophic factor (BDNF), thereby impairing synaptic plasticity. These findings demonstrate a new role for SIRT1 in cognition and a previously unknown microRNA-based mechanism by which SIRT1 regulates these processes. Furthermore, these results describe a separate branch of SIRT1 signalling, in which SIRT1 has a direct role in regulating normal brain function in a manner that is disparate from its cell survival functions, demonstrating its value as a potential therapeutic target for the treatment of central nervous system disorders

Prospects for detection rate of very-high-energy {\gamma}-ray emissions from short {\gamma}-ray bursts with the HADAR experiment

The observation of short gamma ray bursts (SGRBs) in the TeV energy range plays an important role in understanding the radiation mechanism and probing new areas of physics such as Lorentz invariance violation. However, no SGRB has been observed in this energy range due to the short duration of SGRBs and the weakness of current experiments. New experiments with new technology are required to detect sub-TeV SGRBs. In this work, we observe the very high energy (VHE) $\gamma$-ray emissions from SGRBs and calculate the annual detection rate with the High Altitude Detection of Astronomical Radiation HADAR (HADAR) experiment. First, a set of pseudo-SGRB samples is generated and checked using the observations of Fermi-GBM, Fermi-LAT, and SWIFT measurements. The annual detection rate is calculated from these SGRB samples based on the performance of the HADAR instrument. As a result, the HADAR experiment can detect 0.5 SGRB per year if the spectral break-off of $\gamma$-rays caused by the internal absorption is larger than 100 GeV. For a GRB09010-like GRB in HADAR's view, it should be possible to detect approximately 2000 photons considering the internal absorption. With a time delay assumption due to the Lorentz invariance violation effects, a simulated light curve of GRB090510 has evident energy dependence. We hope that the HADAR experiment can perform the SGRB observations and test our calculations in the future

Identification of Enriched Driver Gene Alterations in Subgroups of Non-Small Cell Lung Cancer Patients Based on Histology and Smoking Status

BACKGROUND: Appropriate patient selection is needed for targeted therapies that are efficacious only in patients with specific genetic alterations. We aimed to define subgroups of patients with candidate driver genes in patients with non-small cell lung cancer. METHODS: Patients with primary lung cancer who underwent clinical genetic tests at Guangdong General Hospital were enrolled. Driver genes were detected by sequencing, high-resolution melt analysis, qPCR, or multiple PCR and RACE methods. RESULTS: 524 patients were enrolled in this study, and the differences in driver gene alterations among subgroups were analyzed based on histology and smoking status. In a subgroup of non-smokers with adenocarcinoma, EGFR was the most frequently altered gene, with a mutation rate of 49.8%, followed by EML4-ALK (9.3%), PTEN (9.1%), PIK3CA (5.2%), c-Met (4.8%), KRAS (4.5%), STK11 (2.7%), and BRAF (1.9%). The three most frequently altered genes in a subgroup of smokers with adenocarcinoma were EGFR (22.0%), STK11 (19.0%), and KRAS (12.0%). We only found EGFR (8.0%), c-Met (2.8%), and PIK3CA (2.6%) alterations in the non-smoker with squamous cell carcinoma (SCC) subgroup. PTEN (16.1%), STK11 (8.3%), and PIK3CA (7.2%) were the three most frequently enriched genes in smokers with SCC. DDR2 and FGFR2 only presented in smokers with SCC (4.4% and 2.2%, respectively). Among these four subgroups, the differences in EGFR, KRAS, and PTEN mutations were statistically significant. CONCLUSION: The distinct features of driver gene alterations in different subgroups based on histology and smoking status were helpful in defining patients for future clinical trials that target these genes. This study also suggests that we may consider patients with infrequent alterations of driver genes as having rare or orphan diseases that should be managed with special molecularly targeted therapies

Measurement of the Z/gamma* + b-jet cross section in pp collisions at 7 TeV

The production of b jets in association with a Z/gamma* boson is studied using proton-proton collisions delivered by the LHC at a centre-of-mass energy of 7 TeV and recorded by the CMS detector. The inclusive cross section for Z/gamma* + b-jet production is measured in a sample corresponding to an integrated luminosity of 2.2 inverse femtobarns. The Z/gamma* + b-jet cross section with Z/gamma* to ll (where ll = ee or mu mu) for events with the invariant mass 60 < M(ll) < 120 GeV, at least one b jet at the hadron level with pT > 25 GeV and abs(eta) < 2.1, and a separation between the leptons and the jets of Delta R > 0.5 is found to be 5.84 +/- 0.08 (stat.) +/- 0.72 (syst.) +(0.25)/-(0.55) (theory) pb. The kinematic properties of the events are also studied and found to be in agreement with the predictions made by the MadGraph event generator with the parton shower and the hadronisation performed by PYTHIA.Comment: Submitted to the Journal of High Energy Physic

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns