Yi Chen

Bio: Yi Chen is an academic researcher from Chinese Academy of Sciences. The author has contributed to research in topics: Large Hadron Collider & Medicine. The author has an hindex of 217, co-authored 4342 publications receiving 293080 citations. Previous affiliations of Yi Chen include Rochester Institute of Technology & National Institutes of Health.

Targeting RPL39 and MLF2 reduces tumor initiation and metastasis in breast cancer by inhibiting nitric oxide synthase signaling.

Abstract: We previously described a gene signature for breast cancer stem cells (BCSCs) derived from patient biopsies. Selective shRNA knockdown identified ribosomal protein L39 (RPL39) and myeloid leukemia factor 2 (MLF2) as the top candidates that affect BCSC self-renewal. Knockdown of RPL39 and MLF2 by specific siRNA nanoparticles in patient-derived and human cancer xenografts reduced tumor volume and lung metastases with a concomitant decrease in BCSCs. RNA deep sequencing identified damaging mutations in both genes. These mutations were confirmed in patient lung metastases (n = 53) and were statistically associated with shorter median time to pulmonary metastasis. Both genes affect the nitric oxide synthase pathway and are altered by hypoxia. These findings support that extensive tumor heterogeneity exists within primary cancers; distinct subpopulations associated with stem-like properties have increased metastatic potential.

Cross-section measurements of the Higgs boson decaying into a pair of τ-leptons in proton-proton collisions at √s=13 TeV with the ATLAS detector

Abstract: A measurement of production cross sections of the Higgs boson in proton-proton collisions is presented in the H→ττ decay channel. The analysis is performed using 36.1 fb-1 of data recorded by the ATLAS experiment at the Large Hadron Collider at a center-of-mass energy of s=13 TeV. All combinations of leptonic (τ→vv with =e,μ) and hadronic (τ→hadrons v) τ decays are considered. The H→ττ signal over the expected background from other Standard Model processes is established with an observed (expected) significance of 4.4 (4.1) standard deviations. Combined with results obtained using data taken at 7 and 8 TeV center-of-mass energies, the observed (expected) significance amounts to 6.4 (5.4) standard deviations and constitutes an observation of H→ττ decays. Using the data taken at s=13 TeV, the total cross section in the H→ττ decay channel is measured to be 3.77-0.59+0.60 (stat) -0.74+0.87 (syst) pb, for a Higgs boson of mass 125 GeV assuming the relative contributions of its production modes as predicted by the Standard Model. Total cross sections in the H→ττ decay channel are determined separately for vector-boson-fusion production and gluon-gluon-fusion production to be σH→ττVBF=0.28±0.09 (stat) -0.09+0.11 (syst) pb and σH→ττggF=3.1±1.0 (stat) -1.3+1.6 (syst) pb, respectively. Similarly, results of a fit are reported in the framework of simplified template cross sections. All measurements are in agreement with Standard Model expectations.

Search for heavy ZZ resonances in the l(+) l(-) l(+) l(-) and l(+) l(-) nu(nu)over-bar final states using proton-proton collisions at root s=13 TeV with the ATLAS detector

Abstract: A search for heavy resonances decaying into a pair of $$Z$$ bosons leading to $$\ell ^+\ell ^-\ell ^+\ell ^-$$ and $$\ell ^+\ell ^- u \bar{ u }$$ final states, where $$\ell $$ stands for either an electron or a muon, is presented. The search uses proton–proton collision data at a centre-of-mass energy of 13 $$\text {TeV}$$ corresponding to an integrated luminosity of 36.1 $$\hbox {fb}^{-1}$$ collected with the ATLAS detector during 2015 and 2016 at the Large Hadron Collider. Different mass ranges for the hypothetical resonances are considered, depending on the final state and model. The different ranges span between 200 and 2000 $$\text {GeV}$$ . The results are interpreted as upper limits on the production cross section of a spin-0 or spin-2 resonance. The upper limits for the spin-0 resonance are translated to exclusion contours in the context of Type-I and Type-II two-Higgs-doublet models, while those for the spin-2 resonance are used to constrain the Randall–Sundrum model with an extra dimension giving rise to spin-2 graviton excitations.

Recurrent Mutations of Chromatin-Remodeling Genes and Kinase Receptors in Pheochromocytomas and Paragangliomas

Abstract: Purpose: Pheochromocytomas and paragangliomas (PPGL) are genetically heterogeneous tumors of neural crest origin, but the molecular basis of most PPGLs is unknown. Experimental Design: We performed exome or transcriptome sequencing of 43 samples from 41 patients. A validation set of 136 PPGLs was used for amplicon-specific resequencing. In addition, a subset of these tumors was subjected to microarray-based transcription, protein expression, and histone methylation analysis by Western blotting or immunohistochemistry. In vitro analysis of mutants was performed in cell lines. Results: We detected mutations in chromatin-remodeling genes, including histone-methyltransferases, histone-demethylases, and histones in 11 samples from 8 patients (20%). In particular, we characterized a new cancer syndrome involving PPGLs and giant cell tumors of bone (GCT) caused by a postzygotic G34W mutation of the histone 3.3 gene, H3F3A . Furthermore, mutations in kinase genes were detected in samples from 15 patients (37%). Among those, a novel germline kinase domain mutation of MERT K detected in a patient with PPGL and medullary thyroid carcinoma was found to activate signaling downstream of this receptor. Recurrent germline and somatic mutations were also detected in MET , including a familial case and sporadic PPGLs. Importantly, in each of these three genes, mutations were also detected in the validation group. In addition, a somatic oncogenic hotspot FGFR1 mutation was found in a sporadic tumor. Conclusions: This study implicates chromatin-remodeling and kinase variants as frequent genetic events in PPGLs, many of which have no other known germline driver mutation. MERTK , MET , and H3F3A emerge as novel PPGL susceptibility genes. Clin Cancer Res; 22(9); 2301–10. ©2015 AACR .

Detection template families for gravitational waves from the final stages of binary--black-hole inspirals: Nonspinning case

Abstract: We investigate the problem of detecting gravitational waves from binaries of nonspinning black holes with masses m=5-20M., moving on quasicircular orbits, which are arguably the most promising sources for first-generation ground-based detectors. We analyze and compare all the currently available post-Newtonian approximations for the relativistic two-body dynamics; for these binaries, different approximations predict different waveforms. We then construct examples of detection template families that embed all the approximate models and that could be used to detect the true gravitational-wave signal (but not to characterize accurately its physical parameters). We estimate that the fitting factor for our detection families is greater than or similar to0.95 (corresponding to an event rate loss less than or similar to15%) and we estimate that the discretization of the template family, for similar to10(4) templates, increases the loss to less than or similar to20%.

I and i

Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

KEGG: Kyoto Encyclopedia of Genes and Genomes

Abstract: Kyoto Encyclopedia of Genes and Genomes (KEGG) is a knowledge base for systematic analysis of gene functions in terms of the networks of genes and molecules. The major component of KEGG is the PATHWAY database that consists of graphical diagrams of biochemical pathways including most of the known metabolic pathways and some of the known regulatory pathways. The pathway information is also represented by the ortholog group tables summarizing orthologous and paralogous gene groups among different organisms. KEGG maintains the GENES database for the gene catalogs of all organisms with complete genomes and selected organisms with partial genomes, which are continuously re-annotated, as well as the LIGAND database for chemical compounds and enzymes. Each gene catalog is associated with the graphical genome map for chromosomal locations that is represented by Java applet. In addition to the data collection efforts, KEGG develops and provides various computational tools, such as for reconstructing biochemical pathways from the complete genome sequence and for predicting gene regulatory networks from the gene expression profiles. The KEGG databases are daily updated and made freely available (http://www.genome.ad.jp/kegg/).

limma powers differential expression analyses for RNA-sequencing and microarray studies

Abstract: limma is an R/Bioconductor software package that provides an integrated solution for analysing data from gene expression experiments. It contains rich features for handling complex experimental designs and for information borrowing to overcome the problem of small sample sizes. Over the past decade, limma has been a popular choice for gene discovery through differential expression analyses of microarray and high-throughput PCR data. The package contains particularly strong facilities for reading, normalizing and exploring such data. Recently, the capabilities of limma have been significantly expanded in two important directions. First, the package can now perform both differential expression and differential splicing analyses of RNA sequencing (RNA-seq) data. All the downstream analysis tools previously restricted to microarray data are now available for RNA-seq as well. These capabilities allow users to analyse both RNA-seq and microarray data with very similar pipelines. Second, the package is now able to go past the traditional gene-wise expression analyses in a variety of ways, analysing expression profiles in terms of co-regulated sets of genes or in terms of higher-order expression signatures. This provides enhanced possibilities for biological interpretation of gene expression differences. This article reviews the philosophy and design of the limma package, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.

Atherosclerosis — An Inflammatory Disease

Abstract: Atherosclerosis is an inflammatory disease. Because high plasma concentrations of cholesterol, in particular those of low-density lipoprotein (LDL) cholesterol, are one of the principal risk factors for atherosclerosis,1 the process of atherogenesis has been considered by many to consist largely of the accumulation of lipids within the artery wall; however, it is much more than that. Despite changes in lifestyle and the use of new pharmacologic approaches to lower plasma cholesterol concentrations,2,3 cardiovascular disease continues to be the principal cause of death in the United States, Europe, and much of Asia.4,5 In fact, the lesions of atherosclerosis represent . . .