0000000000174764
AUTHOR
Li Chen
showing 13 related works from this author
The genomic landscape of the Ewing Sarcoma family of tumors reveals recurrent STAG2 mutation.
2014
The Ewing sarcoma family of tumors (EFT) is a group of highly malignant small round blue cell tumors occurring in children and young adults. We report here the largest genomic survey to date of 101 EFT (65 tumors and 36 cell lines). Using a combination of whole genome sequencing and targeted sequencing approaches, we discover that EFT has a very low mutational burden (0.15 mutations/Mb) but frequent deleterious mutations in the cohesin complex subunit STAG2 (21.5% tumors, 44.4% cell lines), homozygous deletion of CDKN2A (13.8% and 50%) and mutations of TP53 (6.2% and 71.9%). We additionally note an increased prevalence of the BRCA2 K3326X polymorphism in EFT patient samples (7.3%) compared …
Global Functional Analyses of Cellular Responses to Pore-Forming Toxins
2011
Here we present the first global functional analysis of cellular responses to pore-forming toxins (PFTs). PFTs are uniquely important bacterial virulence factors, comprising the single largest class of bacterial protein toxins and being important for the pathogenesis in humans of many Gram positive and Gram negative bacteria. Their mode of action is deceptively simple, poking holes in the plasma membrane of cells. The scattered studies to date of PFT-host cell interactions indicate a handful of genes are involved in cellular defenses to PFTs. How many genes are involved in cellular defenses against PFTs and how cellular defenses are coordinated are unknown. To address these questions, we pe…
Analysis of a Parabolic Cross-Diffusion Semiconductor Model with Electron-Hole Scattering
2007
The global-in-time existence of non-negative solutions to a parabolic strongly coupled system with mixed Dirichlet–Neumann boundary conditions is shown. The system describes the time evolution of the electron and hole densities in a semiconductor when electron-hole scattering is taken into account. The parabolic equations are coupled to the Poisson equation for the electrostatic potential. Written in the quasi-Fermi potential variables, the diffusion matrix of the parabolic system contains strong cross-diffusion terms and is only positive semi-definite such that the problem is formally of degenerate type. The existence proof is based on the study of a fully discretized version of the system…
Tbx1 regulates Vegfr3 and is required for lymphatic vessel development
2010
Defects in lymphangiogenesis are added to the broad clinical manifestations of DiGeorge syndrome, caused by deletion of the T box transcription factor Tbx1.
Variable scale effects on hillslope soil erosion during rainfall-runoff processes
2021
Abstract The variation of soil erosion across scales remains a controversial issue. A theoretical framework, coupling the normalized Green-Ampt equation for infiltration, 1D kinematic wave model for overland flow, and WEPP erosion modeling approaches for soil erosion, was used to explain and quantify the direct effect of scale on the soil erosion process. The results show that the relation between interrill erosion and slope length accords with a power-law decreasing trend, while the relation of rill erosion versus slope length shows a power-law increasing trend. Moreover, the power-law scaling of interrill erosion becomes more prominent with an increase of rainfall duration and intensity b…
Analysis of a parabolic cross-diffusion population model without self-diffusion
2006
Abstract The global existence of non-negative weak solutions to a strongly coupled parabolic system arising in population dynamics is shown. The cross-diffusion terms are allowed to be arbitrarily large, whereas the self-diffusion terms are assumed to disappear. The last assumption complicates the analysis since these terms usually provide H 1 estimates of the solutions. The existence proof is based on a positivity-preserving backward Euler–Galerkin approximation, discrete entropy estimates, and L 1 weak compactness arguments. Furthermore, employing the entropy–entropy production method, we show for special stationary solutions that the transient solution converges exponentially fast to its…
Variable power-law scaling of hillslope Hortonian rainfall–runoff processes
2019
Hydrological studies focused on Hortonian rainfall–run-off scaling have found that the run-off depth generally declines with the plot length in power-law scaling. Both the power-law proportional coefficient and the scaling exponent show great variability for specific conditions, but why and how they vary remain unclear. In the present study, the scaling of hillslope Hortonian rainfall–run-off processes is investigated for different rainfall, soil infiltration, and hillslope surface characteristics using the physically based cell-based rainfall-infiltration-run-off model. The results show that both temporally intermittent and steady rainfalls can result in prominent power-law scaling at the …
Full-automatic computer aided system for stem cell clustering using content-based microscopic image analysis
2017
Abstract Stem cells are very original cells that can differentiate into other cells, tissues and organs, which play a very important role in biomedical treatments. Because of the importance of stem cells, in this paper we propose a full-automatic computer aided clustering system to assist scientists to explore potential co-occurrence relations between the cell differentiation and their morphological information in phenotype. In this proposed system, a multi-stage Content-based Microscopic Image Analysis (CBMIA) framework is applied, including image segmentation, feature extraction, feature selection, feature fusion and clustering techniques. First, an Improved Supervised Normalized Cuts (IS…
Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study
2012
BACKGROUND: High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian randomisation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal. METHODS: We performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20,913 myocardial infarction cases, 95,407 controls). Se…
Design of the Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) Study
2010
Background— Recent genome-wide association studies (GWAS) of myocardial infarction (MI) and other forms of coronary artery disease (CAD) have led to the discovery of at least 13 genetic loci. In addition to the effect size, power to detect associations is largely driven by sample size. Therefore, to maximize the chance of finding novel susceptibility loci for CAD and MI, the Coronary ARtery DIsease Genome-wide Replication And Meta-analysis (CARDIoGRAM) consortium was formed. Methods and Results— CARDIoGRAM combines data from all published and several unpublished GWAS in individuals with European ancestry; includes >22 000 cases with CAD, MI, or both and >60 000 controls; and unifies …
Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
2016
Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation o…
Search for an excess of events with an identical flavour lepton pair and significant missing transverse momentum in root s=7 TeV proton-proton collis…
2011
Results are presented of a search for supersymmetric particles decaying into final states with significant missing transverse momentum and exactly two identical flavour leptons (e or mu) of opposite charge in sqrt{s}=7 TeV collisions at the Large Hadron Collider. This channel is particularly sensitive to supersymmetric particle cascade decays producing flavour correlated lepton pairs. Flavour uncorrelated backgrounds are subtracted using a sample of opposite flavour lepton pair events. Observation of an excess beyond Standard Model expectations following this subtraction procedure would offer one of the best routes to measuring the masses of supersymmetric particles. In a data sample corres…
Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial …
2015
BACKGROUND: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated.METHODS: ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population …