3,723 research outputs found

    Measurement of the differential tt̄ cross section in the boosted all-hadronic channel for the CMS experiment at the LHC at √ s = 8TeV

    Get PDF
    The first measurement of the differential tt̄ cross section at using 19.7 fb −1 of all-jet events with boosted high-p T top quark jets collected by the CMS detector at √s =8 TeV is presented. A boosted top jet is one in which the subjets have merged. A data-driven method is used to calculate the standard model background dominated by QCD multijet production. The tt̄ cross section is extracted in bins of measured leading top quark p T using a binned likelihood fit of the invariant mass distribution of top jet candidates. The tt̄ cross section as a function of measured leading top quark pT is then unfolded to parton-level in order to facilitate comparison with theory. This is the first measurement of the differential tt̄ cross secton in the boosted regime in the all-jet channel at √s = 8 TeV

    Prospective Molecular Profiling of Canine Cancers Provides a Clinically Relevant Comparative Model for Evaluating Personalized Medicine (PMed) Trials.

    Get PDF
    Background Molecularly-guided trials (i.e. PMed) now seek to aid clinical decision-making by matching cancer targets with therapeutic options. Progress has been hampered by the lack of cancer models that account for individual-to-individual heterogeneity within and across cancer types. Naturally occurring cancers in pet animals are heterogeneous and thus provide an opportunity to answer questions about these PMed strategies and optimize translation to human patients. In order to realize this opportunity, it is now necessary to demonstrate the feasibility of conducting molecularly-guided analysis of tumors from dogs with naturally occurring cancer in a clinically relevant setting. Methodology A proof-of-concept study was conducted by the Comparative Oncology Trials Consortium (COTC) to determine if tumor collection, prospective molecular profiling, and PMed report generation within 1 week was feasible in dogs. Thirty-one dogs with cancers of varying histologies were enrolled. Twenty-four of 31 samples (77%) successfully met all predefined QA/QC criteria and were analyzed via Affymetrix gene expression profiling. A subsequent bioinformatics workflow transformed genomic data into a personalized drug report. Average turnaround from biopsy to report generation was 116 hours (4.8 days). Unsupervised clustering of canine tumor expression data clustered by cancer type, but supervised clustering of tumors based on the personalized drug report clustered by drug class rather than cancer type. Conclusions Collection and turnaround of high quality canine tumor samples, centralized pathology, analyte generation, array hybridization, and bioinformatic analyses matching gene expression to therapeutic options is achievable in a practical clinical window (\u3c1 \u3eweek). Clustering data show robust signatures by cancer type but also showed patient-to-patient heterogeneity in drug predictions. This lends further support to the inclusion of a heterogeneous population of dogs with cancer into the preclinical modeling of personalized medicine. Future comparative oncology studies optimizing the delivery of PMed strategies may aid cancer drug development

    Extracellular Signal–Regulated Kinase (Erk) Activation by the Pre-T Cell Receptor in Developing Thymocytes in Vivo

    Get PDF
    The first checkpoint in T cell development occurs between the CD4−CD8− and CD4+CD8+ stages and is associated with formation of the pre-T cell receptor (TCR). The signaling mechanisms that drive this progression remain largely unknown. Here, we show that extracellular signal–regulated kinases (ERKs)-1/2 are activated upon engagement of the pre-TCR. Using a novel experimental system, we demonstrate that expression of the pre-TCR by developing thymocytes induces ERK-1/2 activation within the thymus. In addition, the activation of this pre-TCR signaling cascade is mediated through Lck. These findings directly link pre-TCR complex formation with specific downstream signaling components in vivo

    Evidence That γδ versus αβ T Cell Fate Determination Is Initiated Independently of T Cell Receptor Signaling

    Get PDF
    Two types of T cells, αβ and γδ, develop in vertebrates. How these two T cell lineages arise from a common thymic T progenitor is poorly understood. Differentiation of αβ lineage T cells requires the surrogate α chain (pTα), which associates with the T cell receptor (TCR) β chain to form the pre-TCR. γδ lineage development does not appear to involve an obligatory surrogate chain, but instead requires productive rearrangement and expression of both TCR γ and δ genes. It has been proposed that the quality of signals transmitted by the pre-TCR and γδ TCR are distinct and that these “instructive” signals determine the lineage fate of an uncommitted progenitor cell. Here we show that the thymic T progenitor cells (CD25+CD44+c-kit+CD3−CD4−CD8− thymocytes, termed pro-T cells) from young adult mice that have yet to express TCRs can be subdivided based on interleukin 7 receptor (IL-7R) expression. These subsets exhibit differential potential to develop into γδ versus αβ lineage (CD4+CD8+ cells) in the thymus. Upon intrathymic injection, IL-7Rneg-lo pro-T cells generated a 13-fold higher ratio of αβ lineage to γδ lineage cells than did IL-7R+ pro-T cells. Much of this difference was due to a fivefold greater potential of IL-7R+ pro-T cells to develop into TCR-γδ T cells. Evidence indicates that this biased developmental potential is not a result of enhanced TCR-γ gene rearrangement/expression in IL-7R+ pro-T cells. These results indicate that the pro-T cells are heterogeneous in developmental potential before TCR gene rearrangement and suggest that in some precursor cells the initial lineage commitment is independent of TCR-mediated signals

    Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

    Get PDF
    The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

    Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV