Modulation of CD4 T cell function via CD6-targeting

In recent years molecules involved on the immune synapse became successful targets for therapeutic immune modulation. CD6 has been extensively studied, yet, results regarding CD6 biology have been controversial, in spite of the ubiquitous presence of this molecule on virtually all CD4 T cells. We investigated the outcome of murine and human antibodies targeting CD6 domain 1. We found that CD6-targeting had a major impact on the functional specialization of CD4 cells, both human and murine. Differentiation of CD4 T cells towards a Foxp3+ Treg fate was prevented with increasing doses of anti-CD6, while Th1 polarization was favoured. No impact was observed on Th2 or Th17 specialization. These in vitro results provided an explanation for the dose-dependent outcome of in vivo anti-CD6 administration where the anti-inflammatory action is lost at the highest doses. Our data show that therapeutic targeting of the immune synapse may lead to paradoxical dose-dependent effects due to modification of T cell fate.Funded by UID/BIM/50005/2019, project funded by Fundação para a Ciência e a Tecnologia (FCT) / Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) throught Fundos do Orçamento do Estado, pela Fundação para a Ciência e a Tecnologia (FCT) ( PTDC/DTP-FTO/3080/2014 ); and by the project SRecognite Infect - ERA/0003/2015 using national funds through FCT . Funders did not have a role in study design, data collection, analysis, and interpretation, or in the writing of the manuscript

Statin short-term inhibition of insulin sensitivity and secretion during acute phase of ST-elevation myocardial infarction

Hyperglycemia during myocardial infarction (MI) has a strong and direct association with mortality. In stable patients and experimental models, statins favor the elevation of glycaemia. The present study investigated whether short-course treatment with statins during MI can influence glucose homeostasis and thus the clinical outcome. In this prospective study, euglycemic hyperinsulinemic clamp (EHC) was performed at second (D2) and sixth (D6) day after MI in patients randomized to simvastatin (S)10 or 80 mg/day during hospitalization (n = 27). In addition, patients (n = 550) were treated without (WS) or with simvastatin (S) at 20, 40 or 80 mg/day had HOMA2S on admission (D1) and fifth (D5) day after MI. According to EHC, insulin sensitivity increased by 20 +/- 60% in S10 and decreased by -6 +/- 28% in S80 (p = 0.025). Consistently, the changes in HOMA2S between D1 and D5 were 40 +/- 145% (WS), 22 +/- 117% (S20), 16 +/- 61% (S40) and -2% +/- 88% (S80) (p = 0.001). In conclusion, statin during the acute phase of MI reduces insulin sensitivity in a dose-dependent manner.9CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ301465/2017-

Heart Rate Variability Analysis in Revascularized Individuals Submitted to an Anaerobic Potency Test

The objective of this study was to analyze the behavior of autonomic modulation before, during and after the Modified Wingate Test (WanMT), through the analysis of Heart Rate Variability (HRV). Six volunteers between the ages of 40 and 70, post-revascularization procedures (angioplasty and/or surgery, mean duration 10 months), were submitted to supervised training for at least 10 to 14 months. The following protocol, divided into 5 phases, was used: 1) Rest Phase (RP): 180 seconds; 2) Submaximum Phase (SP): 30 seconds; 3) Maximum Phase (MP): 30 seconds; 4) Active Recuperation Phase (ARP); 120 seconds and; 5) Passive Recuperation Phase (PRP): 180 seconds. For the WanMT Test, we selected the load of 3.75% of corporal weight for all volunteers. To analyze the HRV, we used the following parameters: the interval RRr, MNN, SDNN, RMSSD and PNN50. We only observed results for the group according to RMSSD parameters during the rest phase of the test protocol in which the group remained in vagal presence and during all other phases in vagal depression. However, when we analyzed the PNN50, we observed that the group was in medium vagal presence during all of the phases of the test though there was no statistically significant difference (p> 0.05) between the phases. Therefore, we can say that all of the individuals had a similar profile in the autonomic response to the WanMT, confirmed by the parameters studied in the analysis of the HRV in the time domain

Electronic and optical properties of lead iodide

ABSTRACT: Lead iodide (PbI2) is a very important material with a technological applicability as a room-temperature radiation detector. It is a wide-band-gap semiconductor (Eg.2 eV) with high environmental stability efficiency. The performance of the detector cannot be fully understood unless its electronic and optical properties are determined. Recently, its band-gap energy and thermal properties were determined by photoacoustic spectroscopy. A single crystal of PbI2 was grown by the Bridgman method with the c-axis oriented perpendicular to the growth axis. The purpose of this work is to obtain the electronic structure of PbI2, its dielectric functions e 1 and e 2 by ellipsometry and theoretically by full-potential linear muffin-tinorbital ~FPLMTO! method, and the temperature dependence of the measured band-gap energy by optica absorption. The obtained Eg(T) can be fitted by two different methods, leading to Eg ~0 K! and Eg ~300 K!

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Measurement of the t t-bar production cross section in the dilepton channel in pp collisions at sqrt(s) = 7 TeV

The t t-bar production cross section (sigma[t t-bar]) is measured in proton-proton collisions at sqrt(s) = 7 TeV in data collected by the CMS experiment, corresponding to an integrated luminosity of 2.3 inverse femtobarns. The measurement is performed in events with two leptons (electrons or muons) in the final state, at least two jets identified as jets originating from b quarks, and the presence of an imbalance in transverse momentum. The measured value of sigma[t t-bar] for a top-quark mass of 172.5 GeV is 161.9 +/- 2.5 (stat.) +5.1/-5.0 (syst.) +/- 3.6(lumi.) pb, consistent with the prediction of the standard model.Comment: Replaced with published version. Included journal reference and DO

Combined search for the quarks of a sequential fourth generation

Results are presented from a search for a fourth generation of quarks produced singly or in pairs in a data set corresponding to an integrated luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in 2011. A novel strategy has been developed for a combined search for quarks of the up and down type in decay channels with at least one isolated muon or electron. Limits on the mass of the fourth-generation quarks and the relevant Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a simple extension of the standard model with a sequential fourth generation of fermions. The existence of mass-degenerate fourth-generation quarks with masses below 685 GeV is excluded at 95% confidence level for minimal off-diagonal mixing between the third- and the fourth-generation quarks. With a mass difference of 25 GeV between the quark masses, the obtained limit on the masses of the fourth-generation quarks shifts by about +/- 20 GeV. These results significantly reduce the allowed parameter space for a fourth generation of fermions.Comment: Replaced with published version. Added journal reference and DO

Search for anomalous t t-bar production in the highly-boosted all-hadronic final state

A search is presented for a massive particle, generically referred to as a Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are sufficiently massive to produce highly Lorentz-boosted top quarks, which yield collimated decay products that are partially or fully merged into single jets. The analysis uses new methods to analyze jet substructure, providing suppression of the non-top multijet backgrounds. The analysis is based on a data sample of proton-proton collisions at a center-of-mass energy of 7 TeV, corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits in the range of 1 pb are set on the product of the production cross section and branching fraction for a topcolor Z' modeled for several widths, as well as for a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any enhancement in t t-bar production beyond expectations of the standard model for t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version includes a minor typo correction that will be submitted as an erratu

Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets