COMPARATIVE RESEARCH ON THE STROKE RHYTHM OF MEN AND WOMEN KAYAKERS IN THE INTERNATIONAL COMPETITION

The text studied the stroke rate and rhythm of men and women kayakers in the world cup competition on the base of defined division of time phase for each stroke. It is found that the time proportion of the pull and air-work phase in the two sides of men kayakers are both 65% to 35%, while the time proportion of the same phase in the right-side of women kayakers is 66% to 34%, and that in the lefl-side is 69% to 31%; the power time proportion in the right-side of men kayakers is 40% and in the left-side is 41 %, while that in the right-side of women kayakers is 39% and in the lefl-side is 41 %. Men kayakers command a better symmetry and consistency between the left and right side in stroke rhythm than women kayakers. Men kayakers increase the stroke rate mainly accompanied with shortening the air-work time proportion while womenkayakers mainly with shortening the pull time proportion

Spatial analysis of malaria in Anhui province, China

<p>Abstract</p> <p>Background</p> <p>Malaria has re-emerged in Anhui Province, China, and this province was the most seriously affected by malaria during 2005–2006. It is necessary to understand the spatial distribution of malaria cases and to identify highly endemic areas for future public health planning and resource allocation in Anhui Province.</p> <p>Methods</p> <p>The annual average incidence at the county level was calculated using malaria cases reported between 2000 and 2006 in Anhui Province. GIS-based spatial analyses were conducted to detect spatial distribution and clustering of malaria incidence at the county level.</p> <p>Results</p> <p>The spatial distribution of malaria cases in Anhui Province from 2000 to 2006 was mapped at the county level to show crude incidence, excess hazard and spatial smoothed incidence. Spatial cluster analysis suggested 10 and 24 counties were at increased risk for malaria (<it>P </it>< 0.001) with the maximum spatial cluster sizes at < 50% and < 25% of the total population, respectively.</p> <p>Conclusion</p> <p>The application of GIS, together with spatial statistical techniques, provide a means to quantify explicit malaria risks and to further identify environmental factors responsible for the re-emerged malaria risks. Future public health planning and resource allocation in Anhui Province should be focused on the maximum spatial cluster region.</p

Projecting potential spatial and temporal changes in the distribution of Plasmodium vivax and Plasmodium falciparum malaria in China with climate change.

BACKGROUND: Global climate change is likely to increase the geographic range and seasonality of malaria transmission. Areas suitable for distribution of malaria vectors are predicted to increase with climate change but evidence is limited on future distribution of malaria with climate in China. OBJECTIVE: Our aim was to assess a potential effect of climate change on Plasmodium vivax (P. vivax) and Plasmodium falciparum (P. falciparum) malaria under climate change scenarios. METHODS: National malaria surveillance data during 2005-2014 were integrated with corresponding climate data to model current weather-malaria relationship. We used the Generalized Additive Model (GAM) with a spatial component, assuming a quasi-Poisson distribution and including an offset for the population while accounting for potential non-linearity and long-term trend. The association was applied to future climate to project county-level malaria distribution using ensembles of Global Climate Models under two climate scenarios - Representative Concentration Pathways (RCP4.5 and RCP8.5). RESULTS: Climate change could substantially increase P. vivax and P. falciparum malaria, under both climate scenarios, but by larger amount under RCP8.5, compared to the baseline. P. falciparum is projected to increase more than P. vivax. The distributions of P. vivax and P. falciparum malaria are expected to increase in most regions regardless of the climate scenarios. A high percentage (>50%) increases are projected in some counties of the northwest, north, northeast, including northern tip of the northeast China, with a clearer spatial change for P. vivax than P. falciparum under both scenarios, highlighting potential changes in the latitudinal extent of the malaria. CONCLUSION: Our findings suggest that spatial and temporal distribution of P. vivax and P. falciparum malaria in China will change due to future climate change, if there is no policy to mitigate it. These findings are important to guide the malaria elimination goal for China

A covalently bound inhibitor triggers EZH2 degradation through CHIP‐mediated ubiquitination

Abstract Enhancer of zeste homolog 2 (EZH2) has been characterized as a critical oncogene and a promising drug target in human malignant tumors. The current EZH2 inhibitors strongly suppress the enhanced enzymatic function of mutant EZH2 in some lymphomas. However, the recent identification of a PRC2‐ and methyltransferase‐independent role of EZH2 indicates that a complete suppression of all oncogenic functions of EZH2 is needed. Here, we report a unique EZH2‐targeting strategy by identifying a gambogenic acid (GNA) derivative as a novel agent that specifically and covalently bound to Cys668 within the EZH2‐SET domain, triggering EZH2 degradation through COOH terminus of Hsp70‐interacting protein (CHIP)‐mediated ubiquitination. This class of inhibitors significantly suppressed H3K27Me3 and effectively reactivated polycomb repressor complex 2 (PRC2)‐silenced tumor suppressor genes. Moreover, the novel inhibitors significantly suppressed tumor growth in an EZH2‐dependent manner, and tumors bearing a non‐GNA‐interacting C668S‐EZH2 mutation exhibited resistance to the inhibitors. Together, our results identify the inhibition of the signaling pathway that governs GNA‐mediated destruction of EZH2 as a promising anti‐cancer strategy

Effects of partner proteins on BCA2 RING ligase activity

Abstract Background BCA2 is an E3 ligase linked with hormone responsive breast cancers. We have demonstrated previously that the RING E3 ligase BCA2 has autoubiquitination activity and is a very unstable protein. Previously, only Rab7, tetherin, ubiquitin and UBC9 were known to directly interact with BCA2. Methods Here, additional BCA2 binding proteins were found using yeast two-hybrid and bacterial-II-hybrid screening techniques with Human breast and HeLa cDNA libraries. Co-expression of these proteins was analyzed through IHC of TMAs. Investigation of the molecular interactions and effects were examined through a series of in vivo and in vitro assays. Results Ten unique BCA2 interacting proteins were identified, two of which were hHR23a and 14-3-3sigma. Both hHR23a and 14-3-3sigma are co-expressed with BCA2 in breast cancer cell lines and patient breast tumors (n = 105). hHR23a and BCA2 expression was significantly correlated (P = \u3c 0.0001 and P = 0.0113) in both nucleus and cytoplasm. BCA2 expression showed a statistically significant correlation with tumor grade. High cytoplasmic hHR23a trended towards negative nodal status. Binding to BCA2 by hHR23a and 14-3-3sigma was confirmed in vitro using tagged partner proteins and BCA2. hHR23a and 14-3-3sigma effect the autoubiquitination and auto-degradation activity of BCA2. Ubiquitination of hHR23a-bound BCA2 was found to be dramatically lower than that of free BCA2, suggesting that hHR23a promotes the stabilization of BCA2 by inactivating its autoubiquitination activity, without degradation of hHR23a. On the other hand, phosphorylated BCA2 protein is stabilized by interaction with 14-3-3sigma both with and without proteasome inhibitor MG-132 suggesting that BCA2 is regulated by multiple degradation pathways. Conclusions The interaction between BCA2 and hHR23a in breast cancer cells stabilizes BCA2. High expression of BCA2 is correlated with grade in breast cancer, suggesting regulation of this E3 ligase is important to cancer progression

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Inferring structural variant cancer cell fraction

Abstract: We present SVclone, a computational method for inferring the cancer cell fraction of structural variant (SV) breakpoints from whole-genome sequencing data. SVclone accurately determines the variant allele frequencies of both SV breakends, then simultaneously estimates the cancer cell fraction and SV copy number. We assess performance using in silico mixtures of real samples, at known proportions, created from two clonal metastases from the same patient. We find that SVclone’s performance is comparable to single-nucleotide variant-based methods, despite having an order of magnitude fewer data points. As part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) consortium, which aggregated whole-genome sequencing data from 2658 cancers across 38 tumour types, we use SVclone to reveal a subset of liver, ovarian and pancreatic cancers with subclonally enriched copy-number neutral rearrangements that show decreased overall survival. SVclone enables improved characterisation of SV intra-tumour heterogeneity

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Adsorption Behaviors of Cobalt on the Graphite and SiC Surface: A First-Principles Study

Graphite and silicon carbide (SiC) are important materials of fuel elements in High Temperature Reactor-Pebble-bed Modules (HTR-PM) and it is essential to analyze the source term about the radioactive products adsorbed on graphite and SiC surface in HTR-PM. In this article, the adsorption behaviors of activation product Cobalt (Co) on graphite and SiC surface have been studied with the first-principle calculation, including the adsorption energy, charge density difference, density of states, and adsorption ratios. It shows that the adsorption behaviors of Co on graphite and SiC both belong to chemisorption, with an adsorption energy 2.971 eV located at the Hollow site and 6.677 eV located at the hcp-Hollow site, respectively. Combining the charge density difference and density of states, it indicates that the interaction of Co-SiC system is stronger than Co-graphite system. Furthermore, the variation of adsorption ratios of Co on different substrate is obtained by a model of grand canonical ensemble, and it is found that when the temperature is close to 650 K and 1700 K for graphite surface and SiC surface, respectively, the Co adatom on the substrate will desorb dramatically. These results show that SiC layer in fuel element could obstruct the diffusion of Co effectively in normal and accidental operation conditions, but the graphite may become a carrier of Co radioactivity nuclide in the primary circuit of HTR-PM