The rockefeller university

The first observation of the Z boson decaying to four leptons in proton-proton collisions is presented. The analyzed data set corresponds to an integrated luminosity of 5.02 fb(-1) at root s = 7 TeV collected by the CMS detector at the Large Hadron Collider. A pronounced resonance peak, with a statistical significance of 9.7 sigma, is observed in the distribution of the invariant mass of four leptons (electrons and/or muons) with mass and width consistent with expectations for Z boson decays. The branching fraction and cross section reported here are defined by phase space restrictions on the leptons, namely, 80 < m(4l) < 100 GeV, where m(4l) is the invariant mass of the four leptons, and m(ll) > 4 GeV for all pairs of leptons, where m(ll) is the two-lepton invariant mass. The measured branching fraction is B(Z -> 4(l)) = 4.2(-0.8)(+0.9)(stat.) +/- 0.2(syst.)) x 10(-6) and agrees with the standard model prediction of 4.45 x 10(-6). The measured cross section times branchi!

Purpose of review Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent symptomatic infection of the nails, skin and mucosae mostly by Candida albicans. CMC is common in patients with profound primary T-cell immunodeficiency, who often display multiple infectious and autoimmune diseases. Patients with syndromic CMC, including autosomal dominant hyper IgE syndrome (AD-HIES) and autosomal recessive autoimmune polyendocrinopathy syndrome type I (APS-I), display fewer other infections. Patients with isolated CMC (CMCD) rarely display any other severe disease. We review here recent progress in the genetic dissection of these three types of inherited CMC. Recent findings Low IL-17 T-cell proportions were reported in patients with AD-HIES bearing heterozygous STAT3 mutations, prone to CMC and staphylococcal diseases, and in a kindred with autosomal recessive CARD9 deficiency, prone to CMC and other fungal infections. High levels of neutralizing autoantibodies against IL-17 cytokines were documented in patients with APS-I presenting with CMC as their only infectious disease. The first three genetic causes of CMCD were then reported: autosomal recessive IL-17RA and autosomal dominant IL-17F deficiencies and autosomal dominant STAT1 gain-of-function, impairing IL-17-producing T-cell development. Summary Inborn errors of human IL-17 immunity underlie CMC. Impaired IL-17 immunity may therefore account for CMC in other settings, including patients with acquired immunodeficiency.

There is evidence accumulating for nonrandom segregation of one or more chromosomes during mitosis in different cell types. We use cell synchrony and two methods to show that all chromatids of budding yeast segregate randomly and that there is no mother-daughter bias with respect to Watson and Crick-containing strands of DNA.

The mass of the top quark is measured using a sample of t (t) over bar candidate events with one electron or muon and at least four jets in the final state, collected by CMS in pp collisions at root s = 7TeV at the LHC. A total of 5174 candidate events is selected from data corresponding to an integrated luminosity of 5.0 fb(-1). For each event the mass is reconstructed from a kinematic fit of the decay products to a t (t) over bar hypothesis. The top-quark mass is determined simultaneously with the jet energy scale (JES), constrained by the known mass of the W boson in q (q) over bar decays, to be 173.49 +/- 0.43 (stat.+JES)+/- 0.98(syst.) GeV.

Successful cell division requires the precise and timely coordination of chromosomal, cytoskeletal and membrane trafficking events. These processes are regulated by the competing actions of protein kinases and phosphatases. Aurora B is one of the most intensively studied kinases. In conjunction with inner centromere protein (INCENP), borealin (also known as Dasra) and survivin it forms the chromosomal passenger complex (CPC). This complex targets to different locations at differing times during mitosis, where it regulates key mitotic events: correction of chromosome-microtubule attachment errors; activation of the spindle assembly checkpoint; and construction and regulation of the contractile apparatus that drives cytokinesis. Our growing understanding of the CPC has seen it develop from a mere passenger riding on the chromosomes to one of the main controllers of mitosis.

Introduction: Clinical research participants perceptions regarding their experiences during research protocols provide outcome-based insights into the effectiveness of efforts to protect rights and safety, and opportunities to enhance participants clinical research experiences. Use of validated surveys measuring patient-centered outcomes is standard in hospitals, yet no instruments exist to assess outcomes of clinical research processes. Methods: We derived survey questions from data obtained from focus groups comprised of research participants and professionals. We assessed the survey for face/content validity, and privacy/confidentiality protections and fielded it to research participants at 15 centers. We conducted analyses of response rates, sample characteristics, and psychometrics, including survey and item completion and analysis, internal consistency, item internal consistency, criterion-related validity, and item usefulness. Responses were tested for fit into exi!

MicroRNAs (miRNAs) are essential components of gene regulation, but identification of miRNA targets remains a major challenge. Most target prediction and discovery relies on perfect complementarity of the miRNA seed to the 3' untranslated region (UTR). However, it is unclear to what extent miRNAs target sites without seed matches. Here, we performed a transcriptome-wide identification of the endogenous targets of a single miRNA-miR-155-in a genetically controlled manner. We found that approximately 40% of miR-155-dependent Argonaute binding occurs at sites without perfect seed matches. The majority of these noncanonical sites feature extensive complementarity to the miRNA seed with one mismatch. These noncanonical sites confer regulation of gene expression, albeit less potently than canonical sites. Thus, noncanonical miRNA binding sites are widespread, often contain seed-like motifs, and can regulate gene expression, generating a continuum of targeting and regulation.

In vivo cortical recording reveals that indirectly driven neural assemblies can produce reliable and temporally precise spiking patterns in response to stereotyped stimulation. This suggests that despite being fundamentally noisy, the collective activity of neurons conveys information through temporal coding. Stochastic integrate-and-fire models delineate a natural theoretical framework to study the interplay of intrinsic neural noise and spike timing precision. However, there are inherent difficulties in simulating their networks' dynamics in silico with standard numerical discretization schemes. Indeed, the well-posedness of the evolution of such networks requires temporally ordering every neuronal interaction, whereas the order of interactions is highly sensitive to the random variability of spiking times. Here, we answer these issues for perfect stochastic integrate-and-fire neurons by designing an exact event-driven algorithm for the simulation of recurrent networks, with delayed Dirac-like interactions. In addition to being exact from the mathematical standpoint, our proposed method is highly efficient numerically. We envision that our algorithm is especially indicated for studying the emergence of polychronized motifs in networks evolving under spike-timing-dependent plasticity with intrinsic noise.

The results of a search for the pair production of a fourth-generation up-type quark (t') in proton-proton collisions at root s = 7 TeV are presented, using data corresponding to an integrated luminosity of about 5.0 fb(-1) collected by the Compact Muon Solenoid experiment at the LHC. The t' quark is assumed to decay exclusively to a W boson and a b quark. Events with a single isolated electron or muon, missing transverse momentum, and at least four hadronic jets, of which at least one must be identified as a b jet, are selected. No significant excess of events over standard model expectations is observed. Upper limits for the t'(t) over bar' production cross section at 95% confidence level are set as a function of t' mass, and t'-quark production for masses below 570 GeV is excluded. The search is equally sensitive to nonchiral heavy quarks decaying to Wb. In this case, the results can be interpreted as upper limits on the production cross section times the branching fraction to Wb. (C) 2012 CERN. Published by Elsevier B.V. All rights reserved.