On the Origin of Mass and Angular Momentum of Stellar Objects

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Domain structure of human complement C4b extends with increasing NaCl concentration: implications for its regulatory mechanism

During the activation of complement C4 to C4b, the exposure of its thioester domain (TED) is crucial for the attachment of C4b to activator surfaces. In the C4b crystal structure, TED forms an Arg(104)-Glu(1032) salt bridge to tether its neighbouring macroglobulin (MG1) domain. Here, we examined the C4b domain structure to test whether this salt bridge affects its conformation. Dual polarisation interferometry of C4b immobilised at a sensor surface showed that the maximum thickness of C4b increased by 0.46 nm with increase in NaCl concentration from 50 mM to 175 mM NaCl. Analytical ultracentrifugation showed that the sedimentation coefficient s20, w of monomeric C4b of 8.41 S in 50 mM NaCl buffer decreased to 7.98 S in 137 mM NaCl buffer, indicating that C4b became more extended. Small angle X-ray scattering reported similar RG values of 4.89-4.90 nm for C4b in 137-250 mM NaCl. Atomistic scattering modelling of the C4b conformation showed that TED and the MG1 domain were separated by 4.7 nm in 137-250 mM NaCl, this being greater than that of 4.0 nm in the C4b crystal structure. Our data reveal that in low NaCl concentrations, both at surfaces and in solution, C4b forms compact TED-MG1 structures. In solution, physiologically-relevant NaCl concentrations lead to the separation of the TED and MG1 domain, making C4b less able to bind to its complement regulators. These conformational changes are similar to those seen previously for complement C3b, confirming the importance of this salt bridge for regulating both C4b and C3b

Clinicopathological study of renal biopsies after liver transplantation

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Chinese social media reaction to the MERS-CoV and avian influenza A(H7N9) outbreaks

BACKGROUND: As internet and social media use have skyrocketed, epidemiologists have begun to use online data such as Google query data and Twitter trends to track the activity levels of influenza and other infectious diseases. In China, Weibo is an extremely popular microblogging site that is equivalent to Twitter. Capitalizing on the wealth of public opinion data contained in posts on Weibo, this study used Weibo as a measure of the Chinese people's reactions to two different outbreaks: the 2012 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) outbreak, and the 2013 outbreak of human infection of avian influenza A(H7N9) in China. METHODS: Keyword searches were performed in Weibo data collected by The University of Hong Kong's Weiboscope project. Baseline values were determined for each keyword and reaction values per million posts in the days after outbreak information was released to the public. RESULTS: The results show that the Chinese people reacted significantly to both outbreaks online, where their social media reaction was two orders of magnitude stronger to the H7N9 influenza outbreak that happened in China than the MERS-CoV outbreak that was far away from China. CONCLUSIONS: These results demonstrate that social media could be a useful measure of public awareness and reaction to disease outbreak information released by health authorities.published_or_final_versio

Development of human single-chain antibodies against SARS-associated coronavirus.

The outbreak of severe acute respiratory syndrome (SARS), caused by a distinct coronavirus, in 2003 greatly threatened public health in China, Southeast Asia as well as North America. Over 1,000 patients died of the SARS virus, representing 10% of infected people. Like other coronaviruses, the SARS virus also utilizes a surface glycoprotein, namely the spike protein, to infect host cells. The spike protein of SARS virus consists of 1,255 amino acid residues and can be divided into two sub-domains, S1 and S2. The S1 domain mediates the binding of the virus to its receptor angiotensin-converting enzyme 2, which is abundantly distributed on the surface of human lung cells. The S2 domain mediates membrane fusion between the virus and the host cell. Hence two strategies can be used to block the infection of the SARS virus, either by interfering with the binding of the S1 domain to the receptor or by blocking the fusion of the virus with the cell membrane mediated by the S2 domain. Several antibodies against the S1 domain have been generated and all of them are able to neutralize the virus in vitro and in vivo using animal models. Unfortunately, point mutations have been identified in the S1 domain, so that the virus isolated in the future may not be recognized by these antibodies. As no mutation has been found in the S2 domain indicating that this region is more conserved than the S1 domain, it may be a better target for antibody binding. After predicting the immunogenicity of the epitopes of the S2 domain, we chemically synthesized two peptides and also expressed one of them using a recombinant DNA method. We screened a phage displaying library of human single-chain antibodies (ScFv) against the predicted epitopes and obtained a human ScFv which can recognize the SARS virus in vitro

Chinese Social Media Reaction to Information about 42 Notifiable Infectious Diseases

This study aimed to identify what information triggered social media users' responses regarding infectious diseases. Chinese microblogs in 2012 regarding 42 infectious diseases were obtained through a keyword search in the Weiboscope database. Qualitative content analysis was performed for the posts pertinent to each keyword of the day of the year with the highest daily count. Similar posts were grouped and coded. We identified five categories of information that increased microblog traffic pertaining to infectious diseases: news of an outbreak or a case; health education / information; alternative health information / Traditional Chinese Medicine; commercial advertisement / entertainment; and social issues. News unrelated to the specified infectious diseases also led to elevated microblog traffic. Our study showcases the diverse contexts from which increased social media traffic occur. Our results will facilitate better health communication as causes underlying increased social media traffic are revealed.published_or_final_versio

Low dose 13C-Urea breath test (13C-UBT) with citrate is equally reliable for the detection of Helicobacter pylori infection in Chinese

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Simple non-laboratory-based and laboratory-based risk assessment algorithms and nomogram for detecting undiagnosed diabetes mellitus

This journal suppl. entitled: Abstracts of the 10th International Diabetes Federation–Western Pacific Region Congress and the 6th AASD Scientific MeetingBACKGROUND: Early detection for undiagnosed diabetes mellitus (DM), through routine screening periodically, is critical to prevent or delay severe diabetes-related complications. In order to classify high-risk subjects for DM screening, risk algorithms for undiagnosed DM detection have been richly developed and validated in diverse populations and health care settings. However, the majority of risk algorithms developed within Chinese population were developed and validated in low income setting. Furthermore, there are no nomograms for the use in detecting undiagnosed DM, of which are simple-to-use graphical tool to guide decision-making in both routine clinical practice and community setting. The purpose of this study was to develop simple a nomogram to predict the risk of undiagnosed DM for use in asymptomatic general population, based on non-laboratory-based ...postprin

Cobalt chloride pretreatment promotes cardiac differentiation of human embryonic stem cells under atmospheric oxygen level

Our previous study demonstrated the direct involvement of the HIF-1α subunit in the promotion of cardiac differentiation of murine embryonic stem cells (ESCs). We report the use of cobalt chloride to induce HIF-1α stabilization in human ESCs to promote cardiac differentiation. Treatment of undifferentiated hES2 human ESCs with 50μM cobalt chloride markedly increased protein levels of the HIF-1α subunit, and was associated with increased expression of early cardiac specific transcription factors and cardiotrophic factors including NK2.5, vascular endothelial growth factor, and cardiotrophin-1. When pretreated cells were subjected to cardiac differentiation, a notable increase in the occurrence of beating embryoid bodies and sarcomeric actinin-positive cells was observed, along with increased expression of the cardiac-specific markers, MHC-A, MHC-B, and MLC2V. Electrophysiological study revealed increased atrial-and nodal-like cells in the cobalt chloride-pretreated group. Confocal calcium imaging analysis indicated that the maximum upstroke and decay velocities were significantly increased in both noncaffeine and caffeine-induced calcium transient in cardiomyocytes derived from the cobalt chloride-pretreated cells, suggesting these cells were functionally more mature. In conclusion, our study demonstrated that cobalt chloride pretreatment of hES2 human ESCs promotes cardiac differentiation and the maturation of calcium homeostasis of cardiomyocytes derived from ESCs. © 2011 Mary Ann Liebert, Inc.published_or_final_versio

Simple Non-laboratory- and Laboratory-based Risk Assessment Algorithms and Nomogram for Detecting Undiagnosed Diabetes Mellitus

Background: To develop a simple nomogram which can be used to predict the risk of diabetes mellitus (DM) in asymptomatic non-diabetic general population based on non-laboratory-based and laboratory-based risk algorithms. Methods: Anthropometric data, plasma fasting glucose, full lipid profile, exercise habit and family history of DM were collected from Chinese non-diabetic subjects aged 18-70. Logistic regression analysis was performed on the data of a random sample of 2518 subjects to construct non-laboratory-based and laboratory-based risk assessment algorithms for the detection of undiagnosed DM; both algorithms were validated on the data of the remaining sample (n=839). Hosmer-Lemeshow χ2 statistic and area under the receiver-operating characteristic curve (AUC) were employed to assess the calibration and discrimination of the different DM risk algorithms. Results: Of 3357 subjects recruited, 271 (8.1%) had undiagnosed DM defined by fasting glucose≥7.0mmol/L or 2-hour post-load plasma glucose≥11.1mmol/L after oral glucose tolerance test. The non-laboratory-based risk algorithm, with score ranging from 0 to 33, included age, body mass index, family history of DM, regular exercise and uncontrolled blood pressure; the laboratory-based risk algorithm, with score ranging from 0 to 37, added triglyceride level to the risk factors. Both algorithms demonstrated acceptable calibration (Hosmer-Lemeshow test: P=0.229 and P=0.483, respectively) and discrimination (AUC: 0.709 and 0.711, respectively) for the detection of undiagnosed DM. The optimal cutoff point on the receiver-operating characteristic curve was 18 for the detection of undiagnosed DM in both algorithms. Conclusions: Simple-to-use nomogram for detecting undiagnosed DM has been developed using the validated non-laboratory-based and laboratory-based risk algorithms.postprin