5,773 research outputs found

    Siglec receptors impact mammalian lifespan by modulating oxidative stress.

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    Aging is a multifactorial process that includes the lifelong accumulation of molecular damage, leading to age-related frailty, disability and disease, and eventually death. In this study, we report evidence of a significant correlation between the number of genes encoding the immunomodulatory CD33-related sialic acid-binding immunoglobulin-like receptors (CD33rSiglecs) and maximum lifespan in mammals. In keeping with this, we show that mice lacking Siglec-E, the main member of the CD33rSiglec family, exhibit reduced survival. Removal of Siglec-E causes the development of exaggerated signs of aging at the molecular, structural, and cognitive level. We found that accelerated aging was related both to an unbalanced ROS metabolism, and to a secondary impairment in detoxification of reactive molecules, ultimately leading to increased damage to cellular DNA, proteins, and lipids. Taken together, our data suggest that CD33rSiglecs co-evolved in mammals to achieve a better management of oxidative stress during inflammation, which in turn reduces molecular damage and extends lifespan

    Impedance measurements and simulations on the TCT and TDI LHC collimators

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    The LHC collimation system is a critical element for the safe operation of the LHC machine and it is subject to continuous performance monitoring, hardware upgrade and optimization. In this work we will address the impact on impedance of the upgrades performed on the injection protection target dump (TDI), where the absorber material has been changed to mitigate the device heating observed in machine operation, and on selected secondary (TCS) and tertiary (TCT) collimators, where beam position monitors (BPM) have been embedded for faster jaw alignment. Con- cerning the TDI, we will present the RF measurements per- formed before and after the upgrade, comparing the result to heating and tune shift beam measurements. For the TCTs, we will study how the higher order modes (HOM) intro- duced by the BPM addition have been cured by means of ferrite placement in the device. The impedance mitigation campaign has been supported by RF measurements whose results are in good agreement with GdfidL and CST simula- tions. The presence of undamped low frequency modes is proved not to be detrimental to the safe LHC operation

    Heavy-flavour production in Pb-Pb collisions at the LHC, measured with the ALICE detector

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    We present the first results from the ALICE experiment on the nuclear modification factors for heavy-flavour hadron production in Pb-Pb collisions at sqrt{s_NN}=2.76 TeV. Using proton-proton and lead-lead collision samples at sqrt{s}=7 TeV and sqrt{s_NN}=2.76 TeV, respectively, nuclear modification factors R_AA(pt) were measured for D mesons at central rapidity (via displaced decay vertex reconstruction), and for electrons and muons, at central and forward rapidity, respectively.Comment: 8 pages, 5 figures, plenary talk at Quark Matter 2011, Annecy, Franc

    Effect of ω-3 and ω-9 fatty acid rich oils on lipoxygenases and cyclooxygenases enzymes and on the growth of a mammary adenocarcinoma model

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    Background Nutritional factors play a major role in cancer initiation and development. Dietary polyunsaturated fatty acids (PUFAs) have the ability to induce modifications in the activity of lipoxygenase (LOX) and cyclooxygenase (COX) enzymes that affect tumour growth. We studied the effect of two diets enriched in 6% Walnut and Peanut oils that are rich in ω-3 and ω9 PUFAs respectively on a murine mammary gland adenocarcinoma as compared with the control (C) that received commercial diet. Results Peanut oil enriched diet induced an increase in membrane arachidonic acid (AA) content and the cyclooxygenase enzyme derived 12-HHT (p < 0.05) and simultaneously showed decrease in 12-LOX, 15-LOX-2, 15-LOX-1 and PGE activities (p < 0.05) that corresponded to higher apoptosis and lower mitosis seen in this group (p < 0.05). Furthermore, Peanut oil group showed lower T-cell infiltration (p < 0.05), number of metastasis (p < 0.05) and tumour volume (p < 0.05) and longer survival rate compared to other groups. Conclusions The results of the present study showed that Peanut oil-enriched diet protects against mammary cancer development by modulating tumour membrane fatty acids composition and LOX and COX enzyme activities.Fil: Comba, Andrea. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Biología Celular; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Cátedra de Histología,embriología y Genética I; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Maestri, Damian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Berra, María Alejandra. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Biología Celular; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Cátedra de Histología,embriología y Genética I; ArgentinaFil: Garcia, Carolina Paola. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Biología Celular; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Cátedra de Histología,embriología y Genética I; ArgentinaFil: Das, Undurti N.. Jawaharlal Nehru Technological University; India. Undurti Narasimha Das; Estados Unidos. Krishna Institute of Medical Sciences; IndiaFil: Eynard, Aldo Renato. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Biología Celular; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Cátedra de Histología,embriología y Genética I; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Pasqualini, María Eugenia. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Biología Celular; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Cátedra de Histología,embriología y Genética I; Argentin

    Device Therapies Among Patients Receiving Primary Prevention Implantable Cardioverter-Defibrillators in the Cardiovascular Research Network

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    BACKGROUND: Primary prevention implantable cardioverter-defibrillators (ICDs) reduce mortality in selected patients with left ventricular systolic dysfunction by delivering therapies (antitachycardia pacing or shocks) to terminate potentially lethal arrhythmias; inappropriate therapies also occur. We assessed device therapies among adults receiving primary prevention ICDs in 7 healthcare systems. METHODS AND RESULTS: We linked medical record data, adjudicated device therapies, and the National Cardiovascular Data Registry ICD Registry. Survival analysis evaluated therapy probability and predictors after ICD implant from 2006 to 2009, with attention to Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups: left ventricular ejection fraction, 31% to 35%; nonischemic cardiomyopathy \u3c9 \u3emonths\u27 duration; and New York Heart Association class IV heart failure with cardiac resynchronization therapy defibrillator. Among 2540 patients, 35% wereold, 26% were women, and 59% were white. During 27 (median) months, 738 (29%) received ≥1 therapy. Three-year therapy risk was 36% (appropriate, 24%; inappropriate, 12%). Appropriate therapy was more common in men (adjusted hazard ratio [HR], 1.84; 95% confidence interval [CI], 1.43-2.35). Inappropriate therapy was more common in patients with atrial fibrillation (adjusted HR, 2.20; 95% CI, 1.68-2.87), but less common among patients ≥65 years old versus younger (adjusted HR, 0.72; 95% CI, 0.54-0.95) and in recent implants (eg, in 2009 versus 2006; adjusted HR, 0.66; 95% CI, 0.46-0.95). In Centers for Medicare and Medicaid Services Coverage With Evidence Development analysis, inappropriate therapy was less common with cardiac resynchronization therapy defibrillator versus single chamber (adjusted HR, 0.55; 95% CI, 0.36-0.84); therapy risk did not otherwise differ for Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups. CONCLUSIONS: In this community cohort of primary prevention patients receiving ICD, therapy delivery varied across demographic and clinical characteristics, but did not differ meaningfully for Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups

    Comparison of Inappropriate Shocks and Other Health Outcomes Between Single- and Dual-Chamber Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death: Results from the Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter-Defibrillators

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    Background In US clinical practice, many patients who undergo placement of an implantable cardioverter‐defibrillator (ICD) for primary prevention of sudden cardiac death receive dual‐chamber devices. The superiority of dual‐chamber over single‐chamber devices in reducing the risk of inappropriate ICD shocks in clinical practice has not been established. The objective of this study was to compare risk of adverse outcomes, including inappropriate shocks, between single‐ and dual‐chamber ICDs for primary prevention. Methods and Results We identified patients receiving a single‐ or dual‐chamber ICD for primary prevention who did not have an indication for pacing from 15 hospitals within 7 integrated health delivery systems in the Longitudinal Study of Implantable Cardioverter‐Defibrillators from 2006 to 2009. The primary outcome was time to first inappropriate shock. ICD shocks were adjudicated for appropriateness. Other outcomes included all‐cause hospitalization, heart failure hospitalization, and death. Patient, clinician, and hospital‐level factors were accounted for using propensity score weighting methods. Among 1042 patients without pacing indications, 54.0% (n=563) received a single‐chamber device and 46.0% (n=479) received a dual‐chamber device. In a propensity‐weighted analysis, device type was not significantly associated with inappropriate shock (hazard ratio, 0.91; 95% confidence interval, 0.59–1.38 [P=0.65]), all‐cause hospitalization (hazard ratio, 1.03; 95% confidence interval, 0.87–1.21 [P=0.76]), heart failure hospitalization (hazard ratio, 0.93; 95% confidence interval, 0.72–1.21 [P=0.59]), or death (hazard ratio, 1.19; 95% confidence interval, 0.93–1.53 [P=0.17]). Conclusions Among patients who received an ICD for primary prevention without indications for pacing, dual‐chamber devices were not associated with lower risk of inappropriate shock or differences in hospitalization or death compared with single‐chamber devices. This study does not justify the use of dual‐chamber devices to minimize inappropriate shocks

    Effects of new physics in neutrino oscillations in matter

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    A new flavor changing electron neutrino interaction with matter would always dominate the nu_e oscillation probability at sufficiently high neutrino energies. Being suppressed by theta_{13}, the energy scale at which the new effect starts to be relevant may be within the reach of realistic experiments, where the peculiar dependence of the signal with energy could give rise to a clear signature in the nu_e --> nu_tau channel. The latter could be observed by means of a coarse large magnetized detector by exploiting tau --> mu decays. We discuss the possibility of identifying or constraining such effects with a high energy neutrino factory. We also comment on the model independent limits on them.Comment: 11 pages, 5 figure

    The short term debt vs. long term debt puzzle: a model for the optimal mix

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    This paper argues that the existing finance literature is inadequate with respect to its coverage of capital structure of small and medium sized enterprises (SMEs). In particular it is argued that the cost of equity (being both conceptually ill defined and empirically non quantifiable) is not applicable to the capital structure decisions for a large proportion of SMEs and the optimal capital structure depends only on the mix of short and long term debt. The paper then presents a model, developed by practitioners for optimising the debt mix and demonstrates its practical application using an Italian firm's debt structure as a case study

    Linear ubiquitin assembly complex regulates lung epithelial–driven responses during influenza infection

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    Influenza A virus (IAV) is among the most common causes of pneumonia-related death worldwide. Pulmonary epithelial cells are the primary target for viral infection and replication and respond by releasing inflammatory mediators that recruit immune cells to mount the host response. Severe lung injury and death during IAV infection result from an exuberant host inflammatory response. The linear ubiquitin assembly complex (LUBAC), composed of SHARPIN, HOIL-1L, and HOIP, is a critical regulator of NF-κB–dependent inflammation. Using mice with lung epithelial–specific deletions of HOIL-1L or HOIP in a model of IAV infection, we provided evidence that, while a reduction in the inflammatory response was beneficial, ablation of the LUBAC-dependent lung epithelial–driven response worsened lung injury and increased mortality. Moreover, we described a mechanism for the upregulation of HOIL-1L in infected and noninfected cells triggered by the activation of type I IFN receptor and mediated by IRF1, which was maladaptive and contributed to hyperinflammation. Thus, we propose that lung epithelial LUBAC acts as a molecular rheostat that could be selectively targeted to modulate the immune response in patients with severe IAV-induced pneumonia.Fil: Brazee, Patricia L.. Northwestern University; Estados UnidosFil: Morales Nebreda, Luisa. Northwestern University; Estados UnidosFil: Magnani, Natalia Daniela. Northwestern University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; ArgentinaFil: Garcia, Joe G. N.. University of Arizona; Estados UnidosFil: Misharin, Alexander V.. Northwestern University; Estados UnidosFil: Ridge, Karen M.. Northwestern University; Estados UnidosFil: Budinger, G.R. Scott. Northwestern University; Estados UnidosFil: Iwai, Kazuhiro. Kyoto University; JapónFil: Dada, Laura Andrea. Northwestern University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; ArgentinaFil: Sznajder, Jacob I.. Northwestern University; Estados Unido
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