154 research outputs found

    Dependency Parsing by Inference over High-recall Dependency Predictions

    Get PDF

    One-dimensional models of disordered quantum wires: general formalism

    Full text link
    In this work we describe, compile and generalize a set of tools that can be used to analyse the electronic properties (distribution of states, nature of states, ...) of one-dimensional disordered compositions of potentials. In particular, we derive an ensemble of universal functional equations which characterize the thermodynamic limit of all one-dimensional models and which only depend formally on the distributions that define the disorder. The equations are useful to obtain relevant quantities of the system such as density of states or localization length in the thermodynamic limit

    Frustration - how it can be measured

    Full text link
    A misfit parameter is used to characterize the degree of frustration of ordered and disordered systems. It measures the increase of the ground-state energy due to frustration in comparison with that of a relevant reference state. The misfit parameter is calculated for various spin-glass models. It allows one to compare these models with each other. The extension of this concept to other combinatorial optimization problems with frustration, e.g. p-state Potts glasses, graph-partitioning problems and coloring problems is given.Comment: 10 pages, 1 table, no figures, uses revtex.st

    Three-dimensional effects on extended states in disordered models of polymers

    Get PDF
    We study electronic transport properties of disordered polymers in the presence of both uncorrelated and short-range correlated impurities. In our procedure, the actual physical potential acting upon the electrons is replaced by a set of nonlocal separable potentials, leading to a Schr\"odinger equation that is exactly solvable in the momentum representation. We then show that the reflection coefficient of a pair of impurities placed at neighboring sites (dimer defect) vanishes for a particular resonant energy. When there is a finite number of such defects randomly distributed over the whole lattice, we find that the transmission coefficient is almost unity for states close to the resonant energy, and that those states present a very large localization length. Multifractal analysis techniques applied to very long systems demonstrate that these states are truly extended in the thermodynamic limit. These results reinforce the possibility to verify experimentally theoretical predictions about absence of localization in quasi-one-dimensional disordered systems.Comment: 16 pages, REVTeX 3.0, 5 figures on request from FDA ([email protected]). Submitted to Phys. Rev. B. MA/UC3M/09/9

    Anticancer, Biophysical and Computational Investigations of Half-Sandwich Ruthenium(II) Thiosemicarbazone Complexes: The Effect of Arene \u3ci\u3eVersus\u3c/i\u3e Thiacrown Face-Cap

    Get PDF
    A series of half-sandwich ruthenium complexes, two containing an arene face-cap and the other a thiacrown ether face-cap were synthesized to investigate the necessity of the arene for anticancer activity in this class of compounds. The complexes are formulated as [(h6-p-cymene)Ru(dmabTSC)Cl]PF6, [(h6-benzene)Ru(dmabTSC)Cl]PF6 (arene complexes), and [([9]aneS3(dmabTSC)Cl]PF6 (dmabTSC = dimethylaminobenzaldehye thiosemicarbazone). It was observed that none of the complexes showed good anticancer activity in vitro against HCT-116 and Caco-2 (colon adenocarcinoma) cells. All three complexes can bind strongly to calf-thymus DNA with binding constants on the order of 105 M-1. In addition they all bind strongly to human serum albumin with binding constants between 105 and 106 M-1. There appears to be a single binding site on the protein for these complexes. A computational investigation of these complexes and their hydrolysis products was carried out by molecular docking with DNA and topoisomerase II. From this analysis it is noted that the type of face-capping ligand had different effects on the two macromolecules. It is therefore noted that the knowledge gained from this study will be useful in identifying the type of complexes in this class that show useful metallodrug potential

    Integrative analysis of genomic amplification-dependent expression and loss-of-function screen identifies ASAP1 as a driver gene in triple-negative breast cancer progression

    Get PDF
    The genetically heterogeneous triple-negative breast cancer (TNBC) continues to be an intractable disease, due to lack of effective targeted therapies. Gene amplification is a major event in tumorigenesis. Genes with amplification-dependent expression are being explored as therapeutic targets for cancer treatment. In this study, we have applied Analytical Multi-scale Identification of Recurring Events analysis and transcript quantification in the TNBC genome across 222 TNBC tumors and identified 138 candidate genes with positive correlation in copy number gain (CNG) and gene expression. siRNA-based loss-of-function screen of the candidate genes has validated EGFR, MYC, ASAP1, IRF2BP2, and CCT5 genes as drivers promoting proliferation in different TNBC cells. MYC, ASAP1, IRF2BP2, and CCT5 display frequent CNG and concurrent expression over 2173 breast cancer tumors (cBioPortal dataset). More frequently are MYC and ASAP1 amplified in TNBC tumors (>30%, n = 320). In particular, high expression of ASAP1, the ADP-ribosylation factor GTPase-activating protein, is significantly related to poor metastatic relapse-free survival of TNBC patients (n = 257, bc-GenExMiner). Furthermore, we have revealed that silencing of ASAP1 modulates numerous cytokine and apoptosis signaling components, such as IL1B, TRAF1, AIFM2, and MAP3K11 that are clinically relevant to survival outcomes of TNBC patients. ASAP1 has been reported to promote invasion and metastasis in various cancer cells. Our findings that ASAP1 is an amplification-dependent TNBC driver gene promoting TNBC cell proliferation, functioning upstream apoptosis components, and correlating to clinical outcomes of TNBC patients, support ASAP1 as a potential actionable target for TNBC treatment

    Integrative analysis of genomic amplification-dependent expression and loss-of-function screen identifies ASAP1 as a driver gene in triple-negative breast cancer progression

    Get PDF
    The genetically heterogeneous triple-negative breast cancer (TNBC) continues to be an intractable disease, due to lack of effective targeted therapies. Gene amplification is a major event in tumorigenesis. Genes with amplification-dependent expression are being explored as therapeutic targets for cancer treatment. In this study, we have applied Analytical Multi-scale Identification of Recurring Events analysis and transcript quantification in the TNBC genome across 222 TNBC tumors and identified 138 candidate genes with positive correlation in copy number gain (CNG) and gene expression. siRNA-based loss-of-function screen of the candidate genes has validated EGFR, MYC, ASAP1, IRF2BP2, and CCT5 genes as drivers promoting proliferation in different TNBC cells. MYC, ASAP1, IRF2BP2, and CCT5 display frequent CNG and concurrent expression over 2173 breast cancer tumors (cBioPortal dataset). More frequently are MYC and ASAP1 amplified in TNBC tumors (>30%, n = 320). In particular, high expression of ASAP1, the ADP-ribosylation factor GTPase-activating protein, is significantly related to poor metastatic relapse-free survival of TNBC patients (n = 257, bc-GenExMiner). Furthermore, we have revealed that silencing of ASAP1 modulates numerous cytokine and apoptosis signaling components, such as IL1B, TRAF1, AIFM2, and MAP3K11 that are clinically relevant to survival outcomes of TNBC patients. ASAP1 has been reported to promote invasion and metastasis in various cancer cells. Our findings that ASAP1 is an amplification-dependent TNBC driver gene promoting TNBC cell proliferation, functioning upstream apoptosis components, and correlating to clinical outcomes of TNBC patients, support ASAP1 as a potential actionable target for TNBC treatment.Toxicolog

    Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial

    Get PDF
    Item does not contain fulltextBACKGROUND: Platelet transfusion after acute spontaneous primary intracerebral haemorrhage in people taking antiplatelet therapy might reduce death or dependence by reducing the extent of the haemorrhage. We aimed to investigate whether platelet transfusion with standard care, compared with standard care alone, reduced death or dependence after intracerebral haemorrhage associated with antiplatelet therapy use. METHODS: We did this multicentre, open-label, masked-endpoint, randomised trial at 60 hospitals in the Netherlands, UK, and France. We enrolled adults within 6 h of supratentorial intracerebral haemorrhage symptom onset if they had used antiplatelet therapy for at least 7 days beforehand and had a Glasgow Coma Scale score of at least 8. With use of a secure web-based system that concealed allocation and used biased coin randomisation, study collaborators randomly assigned participants (1:1; stratified by hospital and type of antiplatelet therapy) to receive either standard care or standard care with platelet transfusion within 90 min of diagnostic brain imaging. Participants and local investigators giving interventions were not masked to treatment allocation, but allocation was concealed from outcome assessors and investigators analysing data. The primary outcome was shift towards death or dependence rated on the modified Rankin Scale (mRS) at 3 months, and analysed by ordinal logistic regression, adjusted for stratification variables and the Intracerebral Haemorrhage Score. The primary analysis was done in the intention-to-treat population and safety analyses were done in the intention-to-treat and as-treated populations. This trial is registered with the Netherlands Trial Register, number NTR1303, and is now closed. FINDINGS: Between Feb 4, 2009, and Oct 8, 2015, 41 sites enrolled 190 participants. 97 participants were randomly assigned to platelet transfusion and 93 to standard care. The odds of death or dependence at 3 months were higher in the platelet transfusion group than in the standard care group (adjusted common odds ratio 2.05, 95% CI 1.18-3.56; p=0.0114). 40 (42%) participants who received platelet transfusion had a serious adverse event during their hospital stay, as did 28 (29%) who received standard care. 23 (24%) participants assigned to platelet transfusion and 16 (17%) assigned to standard care died during hospital stay. INTERPRETATION: Platelet transfusion seems inferior to standard care for people taking antiplatelet therapy before intracerebral haemorrhage. Platelet transfusion cannot be recommended for this indication in clinical practice. FUNDING: The Netherlands Organisation for Health Research and Development, Sanquin Blood Supply, Chest Heart and Stroke Scotland, French Ministry of Health

    Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21

    Get PDF
    There are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, cis\textit{cis}-acting variants represent an important source of phenotypic variation. Consequently, cis\textit{cis}-regulatory SNPs associated with differential allelic expression are functional candidates for further investigation as disease-causing variants. To investigate whether common variants associated with differential allelic expression were involved in breast cancer susceptibility, a list of genes was established on the basis of their involvement in cancer related pathways and/or mechanisms. Thereafter, using data from a genome-wide map of allelic expression associated SNPs, 313 genetic variants were selected and their association with breast cancer risk was then evaluated in 46,451 breast cancer cases and 42,599 controls of European ancestry ascertained from 41 studies participating in the Breast Cancer Association Consortium. The associations were evaluated with overall breast cancer risk and with estrogen receptor negative and positive disease. One novel breast cancer susceptibility locus on 4q21 (rs11099601) was identified (OR = 1.05, P\textit{P} = 5.6x10−6^{-6}). rs11099601 lies in a 135 kb linkage disequilibrium block containing several genes, including, HELQ\textit{HELQ}, encoding the protein HEL308 a DNA dependant ATPase and DNA Helicase involved in DNA repair, MRPS18C\textit{MRPS18C} encoding the Mitochondrial Ribosomal Protein S18C and FAM175A (ABRAXAS)\textit{FAM175A (ABRAXAS)}, encoding a BRCA1\textit{BRCA1} BRCT domain-interacting protein involved in DNA damage response and double-strand break (DSB) repair. Expression QTL analysis in breast cancer tissue showed rs11099601 to be associated with HELQ \textit{HELQ } (P\textit{P} = 8.28x10−14^{-14}), MRPS18C\textit{MRPS18C} (P\textit{P} = 1.94x10−27^{-27}) and FAM175A \textit{FAM175A } (P\textit{P} = 3.83x10−3^{-3}), explaining about 20%, 14% and 1%, respectively of the variance inexpression of these genes in breast carcinomas.Information regarding funding can be found in the published article or the publisher's website. Funders include Cancer Research UK and the National Institute for Health Research
    • …
    corecore