1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function

HapMap imputed genome-wide association studies (GWAS) have revealed > 50 loci at which common variants with minor allele frequency > 5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 x 10(-8) previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until wholegenome sequencing becomes feasible in large samples

Observation of bound states of solitons in a passively mode-locked fiber laser

We report on an experimental observation of bound states of solitons in a passively mode-locked fiber soliton ring laser. The observed bound solitons are stable and have discrete, fixed soliton separations that are independent of the experimental conditions

A single residue substitution in the receptor-binding domain of H5N1 hemagglutinin is critical for packaging into pseudotyped lentiviral particles

© 2012 Tang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Serological studies for influenza infection and vaccine response often involve microneutralization and hemagglutination inhibition assays to evaluate neutralizing antibodies against human and avian influenza viruses, including H5N1. We have previously characterized lentiviral particles pseudotyped with H5-HA (H5pp) and validated an H5pp-based assay as a safe alternative for high-throughput serological studies in BSL-2 facilities. Here we show that H5-HAs from different clades do not always give rise to efficient production of H5pp and the underlying mechanisms are addressed. Methodology/Findings: We have carried out mutational analysis to delineate the molecular determinants responsible for efficient packaging of HA from A/Cambodia/40808/2005 (H5Cam) and A/Anhui/1/2005 (H5Anh) into H5pp. Our results demonstrate that a single A134V mutation in the 130-loop of the receptor binding domain is sufficient to render H5Anh the ability to generate H5Anh-pp efficiently, whereas the reverse V134A mutation greatly hampers production of H5Cam-pp. Although protein expression in total cell lysates is similar for H5Anh and H5Cam, cell surface expression of H5Cam is detected at a significantly higher level than that of H5Anh. We further demonstrate by several independent lines of evidence that the behaviour of H5Anh can be explained by a stronger binding to sialic acid receptors implicating residue 134. Conclusions: We have identified a single A134V mutation as the molecular determinant in H5-HA for efficient incorporation into H5pp envelope and delineated the underlying mechanism. The reduced binding to sialic acid receptors as a result of the A134V mutation not only exerts a critical influence in pseudotyping efficiency of H5-HA, but has also an impact at the whole virus level. Because A134V substitution has been reported as a naturally occurring mutation in human host, our results may have implications for the understanding of human host adaptation of avian influenza H5N1 virusesThis work was supported by grants from the Research Fund for the Control of Infectious Diseases of Hong Kong (RFCID#08070972), the Area of Excellence Scheme of the University Grants Committee (grant AoE/M-12/-06 of the Hong Kong Special Administrative Region, China), the French Ministry of Health, and the RESPARI project of the Institut Pasteur International Network

Beam based calibration of X-ray pinhole camera in SSRF

The Shanghai Synchrotron Radiation Facility (SSRF) contains a 3.5-GeV storage ring serving as a national X-ray synchrotron radiation user facility characterized by a low emittance and a low coupling. The stability and quality of the electron beams are monitored continuously by an array of diagnostics. In particular, an X-ray pinhole camera is employed in the diagnostics beamline of the ring to characterize the position, size, and emittance of the beam. The performance of the measurement of the transverse electron beam size is given by the width of the point spread function (PSF) of the X-ray pinhole camera. Typically the point spread function of the X-ray pinhole camera is calculated via analytical or numerical method. In this paper we will introduce a new beam based calibration method to derive the width of the PSF online

A Resource Aware MapReduce Based Parallel SVM for Large Scale Image Classifications

Machine learning techniques have facilitated image retrieval by automatically classifying and annotating images with keywords. Among them support vector machines (SVMs) are used extensively due to their generalization properties. However, SVM training is notably a computationally intensive process especially when the training dataset is large. This paper presents RASMO, a resource aware MapReduce based parallel SVM algorithm for large scale image classifications which partitions the training data set into smaller subsets and optimizes SVM training in parallel using a cluster of computers. A genetic algorithm based load balancing scheme is designed to optimize the performance of RASMO in heterogeneous computing environments. RASMO is evaluated in both experimental and simulation environments. The results show that the parallel SVM algorithm reduces the training time significantly compared with the sequential SMO algorithm while maintaining a high level of accuracy in classifications.National Basic Research Program (973) of China under Grant 2014CB34040

A Garlic Derivative, S-allylcysteine (SAC), Suppresses Proliferation and Metastasis of Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is highly malignant and metastatic. Currently, there is no effective chemotherapy for patients with advanced HCC leading to an urgent need to seek for novel therapeutic options. We aimed to investigate the effect of a garlic derivative, S-allylcysteine (SAC), on the proliferation and metastasis of HCC. Methodology/Principal Findings: A series of in vitro experiments including MTT, colony-forming, wound-healing, invasion, apoptosis and cell cycle assays were performed to examine the anti-proliferative and anti-metastatic effects of SAC on a metastatic HCC cell line MHCC97L. The therapeutic values of SAC single and combined with cisplatin treatments were examined in an in vivo orthotopic xenograft liver tumor model. The result showed that the proliferation rate and colony-forming abilities of MHCC97L cells were suppressed by SAC together with significant suppression of the expressions of proliferation markers, Ki-67 and proliferating cell nuclear antigen (PCNA). Moreover, SAC hindered the migration and invasion of MHCC97L cells corresponding with up-regulation of E-cadherin and down-regulation of VEGF. Furthermore, SAC significantly induced apoptosis and necrosis of MHCC97L cells through suppressing Bcl-xL and Bcl-2 as well as activating caspase-3 and caspase-9. In addition, SAC could significantly induce the S phase arrest of MHCC97L cells together with down-regulation of cdc25c, cdc2 and cyclin B1. In vivo xenograft liver tumor model demonstrated that SAC single or combined with cisplatin treatment inhibited the progression and metastasis of HCC tumor. Conclusions/Significance: Our data demonstrate the anti-proliferative and anti-metastatic effects of SAC on HCC cells and suggest that SAC may be a potential therapeutic agent for the treatment of HCC patients. © 2012 Ng et al.published_or_final_versio

Effect of real-time computer-aided polyp detection system (ENDO-AID) on adenoma detection in endoscopists-in-training: a randomized trial

Background The effect of computer-aided polyp detection (CADe) on adenoma detection rate (ADR) among endoscopists-in-training remains unknown. Methods We performed a single-blind, parallel-group, randomized controlled trial in Hong Kong between April 2021 and July 2022 (NCT04838951). Eligible subjects undergoing screening/surveillance/diagnostic colonoscopies were randomized 1:1 to receive colonoscopies with CADe (ENDO-AID(OIP-1), Olympus Co., Japan) or not (control) during withdrawal. Procedures were performed by endoscopists-in-training with <500 procedures and <3 years’ experience. Randomization was stratified by patient age, sex, and endoscopist experience (beginner vs intermediate-level, <200 vs 200-500 procedures). Image enhancement and distal attachment devices were disallowed. Subjects with incomplete colonoscopies or inadequate bowel preparation were excluded. Treatment allocation was blinded to outcome assessors. The primary outcome was ADR. Secondary outcomes were ADR for different adenoma sizes and locations, mean number of adenomas, and non-neoplastic resection rate. Results 386 and 380 subjects were randomized to CADe and control groups, respectively. The overall ADR was significantly higher in CADe than control group (57.5% vs 44.5%, adjusted relative risk 1.41, 95%CI 1.17-1.72, p<0.001). The ADRs for <5mm (40.4% vs 25.0%) and 5-10mm adenomas (36.8% vs 29.2%) were higher in CADe group. The ADRs were higher in CADe group in both right (42.0% vs 30.8%) and left colon (34.5% vs 27.6%), but there was no significant difference in advanced ADR. The ADRs were higher in CADe group among beginners (60.0% vs 41.9%) and intermediate-level endoscopists (56.5% vs 45.5%). Mean number of adenomas (1.48 vs 0.86) and non-neoplastic resection rate were higher in CADe group (52.1% vs 35.0%). Conclusions Among endoscopists-in-training, the use of CADe during colonoscopies was associated with increased overall ADR. (ClinicalTrials.gov: NCT04838951

Engaging service users and carers in health and social care education: : challenges and opportunities in the Chinese Community

This is an accepted manuscript of an article published by Taylor & Francis Group in Social Work Education on 25 June 2010, available online at: http://dx.doi.org/10.1080/02615479.2010.491542.Service users' and carers' involvement in health and social care education has become a mainstream activity in Britain. However, members from black and minority ethnic communities (BME) remain under-represented in this area of participation. In this article, we will take the readers across the globe to explore the difficulties and opportunities of engaging such an under-represented group, the Chinese community. The journey will begin in Britain where barriers to engagement of service users and carers from the Chinese community will be discussed. We will then travel to Hong Kong, a cosmopolitan city, where successful engagement in work with Chinese service users and carers will be explored. Throughout the journey, we will highlight the importance of the consideration of cultural factors, particularly Confucian beliefs such as social harmony and collectivism, when working with Chinese people. We will also fully explore the issue of ‘trust’ as a culturally laden concept in Chinese societies and its significance for successful engagement in work with Chinese service users and carers in different parts of the world.Peer reviewedFinal Accepted Versio