Trace initial interaction from final state observable in relativistic heavy ion collisions

In order to trace the initial interaction in ultra-relativistic heavy ion collision in all azimuthal directions, two azimuthal multiplicity-correlation patterns -- neighboring and fixed-to-arbitrary angular-bin correlation patterns -- are suggested. From the simulation of Au + Au collisions at 200 GeV by using the Monte Carlo models RQMD with hadron re-scattering and AMPT with and without string melting, we observe that the correlation patterns change gradually from out-of-plane preferential one to in-plane preferential one when the centrality of collision shifts from central to peripheral, meanwhile the anisotropic collective flow v_2 keeps positive in all cases. This regularity is found to be model and collision energy independent. The physics behind the two opposite trends of correlation patterns, in particular, the presence of out-of-plane correlation patterns at RHIC energy, are discussed.Comment: 5pages, 4figure

Perspective on Therapeutic Strategies of Leukemia Treatment — Focus on Arsenic Compounds

Leukemia is a type of cancer of the body’s blood-forming tissues, including the bone marrow and the lymphatic system. Treatments for leukemia are complex, depending upon the type of leukemia and other factors. Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) and accounts for approximately 10-15% of all cases of AML in adults. Arsenic and its compounds are widely distributed in the environment and have been used medicinally for over 2,000 years. In fact, investigators from China and the USA have demonstrated that treatment with ATO (As2O3, AsIII) results in complete remission in 90% of relapsed APL patients since mid-1990s. Moreover, As2S2 or As4S4, also known as realgar, has been gaining increasing attention and is traditionally used to treat certain types of hematological disorders including chronic myeloid leukemia (CML), AML, myelodysplastic syndrome (MDS) and MDS/AML in China. In this chapter, we first highlight the pharmacokinetics of ATO and realgar in leukemia patients and/or healthy volunteer. We will further summarize the detailed mechanisms underlying the cytocidal effects of these arsenic compounds. We also provide detailed insight into potential future clinical application of those promising candidates endowed with potent antitumor activities in view of combination with arsenic compounds

Truncated KCNQ1 mutant, A178fs/105, forms hetero-multimer channel with wild-type causing a dominant-negative suppression due to trafficking defect

AbstractWe identified a novel mutation Ala178fs/105 missing S3–S6 and C-terminus portions of KCNQ1 channel. Ala178fs/105-KCNQ1 expressed in COS-7 cells demonstrated no current expression. Co-expression with wild-type (WT) revealed a dominant-negative effect, which suggests the formation of hetero-multimer by mutant and WT. Confocal laser microscopy displayed intracellular retention of Ala178fs/105-KCNQ1 protein. Co-expression of the mutant and WT also increased intracellular retention of channel protein compared to WT alone. Our findings suggest a novel mechanism for LQT1 that the truncated S1–S2 KCNQ1 mutant forms hetero-multimer and cause a dominant-negative effect due to trafficking defect

Comparison of Gross Primary Productivity Derived from GIMMS NDVI3g, GIMMS, and MODIS in Southeast Asia

Gross primary production (GPP) plays an important role in the net ecosystem exchange of CO2 between the atmosphere and terrestrial ecosystems. It is particularly important to monitor GPP in Southeast Asia because of increasing rates of tropical forest degradation and deforestation in the region in recent decades. The newly available, improved, third generation Normalized Difference Vegetation Index (NDVI3g) from the Global Inventory Modelling and Mapping Studies (GIMMS) group provides a long temporal dataset, from July 1981 to December 2011, for terrestrial carbon cycle and climate response research. However, GIMMS NDVI3g-based GPP estimates are not yet available. We applied the GLOPEM-CEVSA model, which integrates an ecosystem process model and a production efficiency model, to estimate GPP in Southeast Asia based on three independent results of the fraction of photosynthetically active radiation absorbed by vegetation (FPAR) from GIMMS NDVI3g (GPPNDVI3g), GIMMS NDVI1g (GPPNDVI1g), and the Moderate Resolution Imaging Spectroradiometer (MODIS) MOD15A2 FPAR product (GPPMOD15). The GPP results were validated using ground data from eddy flux towers located in different forest biomes, and comparisons were made among the three GPPs as well as the MOD17A2 GPP products (GPPMOD17). Based on validation with flux tower derived GPP estimates the results show that GPPNDVI3g is more accurate than GPPNDVI1g and is comparable in accuracy with GPPMOD15. In addition, GPPNDVI3g and GPPMOD15 have good spatial-temporal consistency. Our results indicate that GIMMS NDVI3g is an effective dataset for regional GPP simulation in Southeast Asia, capable of accurately tracking the variation and trends in long-term terrestrial ecosystem GPP dynamics

Thermodynamics of deformed AdS5_5 model with a positive/negative quadratic correction in graviton-dilaton system

By solving the Einstein equations of the graviton coupling with a real scalar dilaton field, we establish a general framework to self-consistently solve the geometric background with black-hole for any given phenomenological holographic models. In this framwork, we solve the black-hole background, the corresponding dilaon field and the dilaton potential for the deformed AdS$_5$ model with a positive/negative quadratic correction. We systematically investigate the thermodynamical properties of the deformed AdS$_5$ model with a positive and negative quadratic correction, respectively, and compare with lattice QCD on the results of the equation of state, the heavy quark potential, the Polyakov loop and the spatial Wilson loop. We find that the bulk thermodynamical properties are not sensitive to the sign of the quadratic correction, and the results of both deformed holographic QCD models agree well with lattice QCD result for pure SU(3) gauge theory. However, the results from loop operators favor a positive quadratic correction, which agree well with lattice QCD result. Especially, the result from the Polyakov loop excludes the model with a negative quadratic correction in the warp factor of ${\rm AdS}_5$.Comment: 26 figures,36 pages,V.3: an appendix,more equations and references added,figures corrected,published versio

Separase Phosphosite Mutation Leads to Genome Instability and Primordial Germ Cell Depletion during Oogenesis

To ensure equal chromosome segregation and the stability of the genome during cell division, Separase is strictly regulated primarily by Securin binding and inhibitory phosphorylation. By generating a mouse model that contained a mutation to the inhibitory phosphosite of Separase, we demonstrated that mice of both sexes are infertile. We showed that Separase deregulation leads to chromosome mis-segregation, genome instability, and eventually apoptosis of primordial germ cells (PGCs) during embryonic oogenesis. Although the PGCs of mutant male mice were completely depleted, a population of PGCs from mutant females survived Separase deregulation. The surviving PGCs completed oogenesis but produced deficient initial follicles. These results indicate a sexual dimorphism effect on PGCs from Separase deregulation, which may be correlated with a gender-specific discrepancy of Securin. Our results reveal that Separase phospho-regulation is critical for genome stability in oogenesis. Furthermore, we provided the first evidence of a pre-zygotic mitotic chromosome segregation error resulting from Separase deregulation, whose sex-specific differences may be a reason for the sexual dimorphism of aneuploidy in gametogenesis

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