1,587 research outputs found

    Triad3a induces the degradation of early necrosome to limit RipK1-dependent cytokine production and necroptosis.

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    Understanding the molecular signaling in programmed cell death is vital to a practical understanding of inflammation and immune cell function. Here we identify a previously unrecognized mechanism that functions to downregulate the necrosome, a central signaling complex involved in inflammation and necroptosis. We show that RipK1 associates with RipK3 in an early necrosome, independent of RipK3 phosphorylation and MLKL-induced necroptotic death. We find that formation of the early necrosome activates K48-ubiquitin-dependent proteasomal degradation of RipK1, Caspase-8, and other necrosomal proteins. Our results reveal that the E3-ubiquitin ligase Triad3a promotes this negative feedback loop independently of typical RipK1 ubiquitin editing enzymes, cIAPs, A20, or CYLD. Finally, we show that Triad3a-dependent necrosomal degradation limits necroptosis and production of inflammatory cytokines. These results reveal a new mechanism of shutting off necrosome signaling and may pave the way to new strategies for therapeutic manipulation of inflammatory responses

    Search for Second-Generation Scalar Leptoquarks in ppˉ\bm{p \bar{p}} Collisions at s\sqrt{s}=1.96 TeV

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    Results on a search for pair production of second generation scalar leptoquark in ppˉp \bar{p} collisions at s\sqrt{s}=1.96 TeV are reported. The data analyzed were collected by the CDF detector during the 2002-2003 Tevatron Run II and correspond to an integrated luminosity of 198 pb1^{-1}. Leptoquarks (LQ) are sought through their decay into (charged) leptons and quarks, with final state signatures represented by two muons and jets and one muon, large transverse missing energy and jets. We observe no evidence for LQLQ production and derive 95% C.L. upper limits on the LQLQ production cross sections as well as lower limits on their mass as a function of β\beta, where β\beta is the branching fraction for LQμqLQ \to \mu q.Comment: 9 pages (3 author list) 5 figure

    SUPPORT FOR COLLABORATIVE AUTHORING VIA EMAIL - THE MESSIE ENVIRONMENT

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    MESSIE is a collaborative authoring environment to support the production of large-scale documents by teams of geographically distributed groups of authors working with hetereogenous systems. The environment allows authors to submit text at various stages of gestation (e.g. list of topics, first draft) to a shared filestore via email. All authors collaborating on a document can read each others’ contributions, and add suggestions, comments and additional material directly to the document. The system integrates automatically answered electronic mail, shared file store administration, and a version control tool in a UNIX environment. The paper describes design and implementation strategy, and reports observations and a number of changes which were made during a 4-month trial period with three collaborative authoring teams

    Performance of the CMS Cathode Strip Chambers with Cosmic Rays

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    The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

    Local and systemic immunomodulatory mechanisms triggered by Human Papillomavirus transformed cells: a potential role for G-CSF and neutrophils

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    Cervical cancer is the last stage of a series of molecular and cellular alterations initiated with Human Papillomavirus (HPV) infection. The process involves immune responses and evasion mechanisms, which culminates with tolerance toward tumor antigens. Our objective was to understand local and systemic changes in the interactions between HPV associated cervical lesions and the immune system as lesions progress to cancer. Locally, we observed higher cervical leukocyte infiltrate, reflected by the increase in the frequency of T lymphocytes, neutrophils and M2 macrophages, in cancer patients. We observed a strong negative correlation between the frequency of neutrophils and T cells in precursor and cancer samples, but not cervicitis. In 3D tumor cell cultures, neutrophils inhibited T cell activity, displayed longer viability and longer CD16 expression half-life than neat neutrophil cultures. Systemically, we observed higher plasma G-CSF concentration, higher frequency of immature low density neutrophils, and tolerogenic monocyte derived dendritic cells, MoDCs, also in cancer patients. Interestingly, there was a negative correlation between T cell activation by MoDCs and G-CSF concentration in the plasma. Our results indicate that neutrophils and G-CSF may be part of the immune escape mechanisms triggered by cervical cancer cells, locally and systemically, respectively.Tis study was supported by Sao Paulo Research foundation: grants 2008/57889-1, 2010/20010-4, 2014/19326-6, by the Brazilian National Counsel of Technological and Scientifc Development: grant 573799/2008-3. KLFA and RAMR had PhD fellowships by Sao Paulo Research Foundation, CRSF has a Coordination for the Improvement of Higher Education Personnel PhD fellowship. We thank the Pathology Department of the School of Medicine, coordinated by Prof. Venâncio Avancini Ferreira Alves, Universidade de São Paulo for the slides containing histological samples from the biopsies used in this study. We thank Sandra Alexandre Alves for her technical support.info:eu-repo/semantics/publishedVersio

    Measurement of the Dipion Mass Spectrum in X(3872) -> J/Psi Pi+ Pi- Decays

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    We measure the dipion mass spectrum in X(3872)--> J/Psi Pi+ Pi- decays using 360 pb-1 of pbar-p collisions at 1.96 TeV collected with the CDF II detector. The spectrum is fit with predictions for odd C-parity (3S1, 1P1, and 3DJ) charmonia decaying to J/Psi Pi+ Pi-, as well as even C-parity states in which the pions are from Rho0 decay. The latter case also encompasses exotic interpretations, such as a D0-D*0Bar molecule. Only the 3S1 and J/Psi Rho hypotheses are compatible with our data. Since 3S1 is untenable on other grounds, decay via J/Psi Rho is favored, which implies C=+1 for the X(3872). Models for different J/Psi-Rho angular momenta L are considered. Flexibility in the models, especially the introduction of Rho-Omega interference, enable good descriptions of our data for both L=0 and 1.Comment: 7 pages, 4 figures -- Submitted to Phys. Rev. Let

    Achieving a Preoperative Target HbA1c of < 69 mmol/mol in Elective Vascular and Orthopedic Surgery: A Retrospective Single Center Observational Study

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    Introduction Diabetes mellitus (DM) is present in 10–15% of the surgical population. It is a known risk factor for adverse postoperative outcomes. UK perioperative guidance recommends optimizing glycemic control preoperatively, aiming for a target glycated hemoglobin (HbA1c) of < 69 mmol/mol. However, real-world compliance with this guidance remains unknown. The aim of our study was to determine how many patients with DM undergoing elective orthopedic and vascular surgery had a preoperative HbA1c of < 69 mmol/mol. We also reviewed the surgical reasons for non-concordance with the recommended preoperative HbA1c target. Methods This was a retrospective observational study of 1000 consecutive patients who had been referred for elective vascular and orthopedic surgery at a large tertiary center. Data were collected on these patients, both those with and without DM, between January 2016 and February 2017. Electronic databases were used to collect information on the patients’ preoperative HbA1c concentration and to determine whether there was a resulting delay in surgery when the preoperative HbA1c target of < 69 mmol/mol was exceeded. Results Of the 1000 patients referred for surgery (500 orthopedic and 500 vascular patients) included in the study, 201 (20%) had diabetes. Among these 201 people with DM, 155 (77%) had a preoperative HbA1c < 69 mmol/mol. Among the 46 people with DM whose HbA1c exceeded the recommended target, 41 were operated on despite the high HbA1c level, and only five had their surgery deferred or canceled due to suboptimal preoperative glycemic control. Conclusions Our data shows that the majority (77% ) of people undergoing elective vascular and orthopedic surgery were able to achieve a target HbA1c of < 69 mmol/mol. The current preoperative guidance is therefore achievable in a real-life setting. However, as is stated in the national guidance, this target should only be used where it is safe to do so and a degree of clinical discretion is necessary

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

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    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

    Visualizing chemical states and defects induced magnetism of graphene oxide by spatially-resolved-X-ray microscopy and spectroscopy

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    [[abstract]]This investigation studies the various magnetic behaviors of graphene oxide (GO) and reduced graphene oxides (rGOs) and elucidates the relationship between the chemical states that involve defects therein and their magnetic behaviors in GO sheets. Magnetic hysteresis loop reveals that the GO is ferromagnetic whereas photo-thermal moderately reduced graphene oxide (M-rGO) and heavily reduced graphene oxide (H-rGO) gradually become paramagnetic behavior at room temperature. Scanning transmission X-ray microscopy and corresponding X-ray absorption near-edge structure spectroscopy were utilized to investigate thoroughly the variation of the C 2p(π*) states that are bound with oxygen-containing and hydroxyl groups, as well as the C 2p(σ*)-derived states in flat and wrinkle regions to clarify the relationship between the spatially-resolved chemical states and the magnetism of GO, M-rGO and H-rGO. The results of X-ray magnetic circular dichroism further support the finding that C 2p(σ*)-derived states are the main origin of the magnetism of GO. Based on experimental results and first-principles calculations, the variation in magnetic behavior from GO to M-rGO and to H-rGO is interpreted, and the origin of ferromagnetism is identified as the C 2p(σ*)- derived states that involve defects/vacancies rather than the C 2p(π*) states that are bound with oxygen-containing and hydroxyl groups on GO sheets.[[notice]]補正完
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