Quasivariational solutions for first order quasilinear equations with gradient constraint

We prove the existence of solutions for an evolution quasi-variational inequality with a first order quasilinear operator and a variable convex set, which is characterized by a constraint on the absolute value of the gradient that depends on the solution itself. The only required assumption on the nonlinearity of this constraint is its continuity and positivity. The method relies on an appropriate parabolic regularization and suitable {\em a priori} estimates. We obtain also the existence of stationary solutions, by studying the asymptotic behaviour in time. In the variational case, corresponding to a constraint independent of the solution, we also give uniqueness results

The regulator LdhR and the d-lactate dehydrogenase LdhA of Burkholderia multivorans play a role in carbon overflow and in planktonic cellular aggregates formation

This paper version is the accepted manuscript posted online 21 July 2017. It has peer-review. This publication hasn't any creative commons license associated. The deposited article version contains attached the supplementary materials within the pdf.LysR-type transcriptional regulators (LTTR) are the most commonly found regulators in Burkholderia cepacia complex, comprising opportunistic pathogens causing chronic respiratory infections in cystic fibrosis (CF) patients. Despite LTTRs being global regulators of pathogenicity in several bacteria, few have been characterized in Burkholderia Here, we showed that gene ldhR of B. multivorans encoding a LTTR is co-transcribed with ldhA encoding a d-lactate dehydrogenase, and evaluate their implication in virulence traits like exopolysaccharide (EPS) synthesis and biofilm formation. Comparison of wild-type (WT) and its isogenic ΔldhR mutant grown in medium with 2% d-glucose revealed a negative impact on EPS biosynthesis and on cells' viability in the presence of LdhR. Loss of viability in WT cells was caused by intracellular acidification as consequence of cumulative organic acids secretion including d-lactate, this last one absent from the ΔldhR mutant supernatant. Furthermore, LdhR is implicated in the formation of planktonic cellular aggregates. WT cell aggregates reached 1000 μm after 24 hours in liquid cultures; in contrast to ΔldhR mutant aggregates that never grew more than 60 μm. Overexpression of d-lactate dehydrogenase LdhA in the ΔldhR mutant partially restored formed aggregates size, suggesting a role for fermentation inside aggregates. Similar results were obtained for surface-attached biofilms, with WT cells producing more biofilm. A systematic evaluation of planktonic aggregates in Burkholderia CF clinical isolates showed aggregates in 40 out of 74. As CF patients' lung environment is microaerophilic and bacteria are found as free aggregates/biofilms, LdhR and LdhA might have central roles in adaptation to this environment.IMPORTANCE Cystic fibrosis patients often suffer from chronic respiratory infections caused by several microorganisms. Among them are the Burkholderia cepacia complex bacteria which cause progressive deterioration of lung function and, in some patients, might develop into fatal necrotizing pneumoniae with bacteremia, known as "cepacia syndrome". Burkholderia pathogenesis is multifactorial since they express several virulence factors, form biofilms, and are highly resistant to antimicrobial compounds, making their eradication from the CF patients' airways very difficult. As Burkholderia is commonly found in the CF lungs in the form of cell aggregates and biofilms, the need to investigate the mechanisms of cellular aggregation is obvious. In this study we demonstrate the importance of a d-lactate dehydrogenase and a regulator, in regulating carbon overflow, cellular aggregates and surface-attached biofilm formation. This not only enhances our understanding of Burkholderia pathogenesis, but can also lead to the development of drugs against these proteins to circumvent biofilm formation.Instituto Gulbenkian de Ciência (Gene Expression Unit); Programa Operacional 833 Regional de Lisboa 2020 grant: (LISBOA-01-0145-FEDER-007317); Fundação para a Ciência e a Tecnologia grants: (PTDC/QUI-BIQ/118260/2010, UID/BIO/04565/2013, SFRH/BPD/86475/2012).info:eu-repo/semantics/acceptedVersio

Elliptic flow of charged particles in Pb-Pb collisions at 2.76 TeV

We report the first measurement of charged particle elliptic flow in Pb-Pb collisions at 2.76 TeV with the ALICE detector at the CERN Large Hadron Collider. The measurement is performed in the central pseudorapidity region (|$\eta$|<0.8) and transverse momentum range 0.2< $p_{\rm T}$< 5.0 GeV/$c$. The elliptic flow signal v$_2$, measured using the 4-particle correlation method, averaged over transverse momentum and pseudorapidity is 0.087 $\pm$ 0.002 (stat) $\pm$ 0.004 (syst) in the 40-50% centrality class. The differential elliptic flow v$_2(p_{\rm T})$ reaches a maximum of 0.2 near $p_{\rm T}$ = 3 GeV/$c$. Compared to RHIC Au-Au collisions at 200 GeV, the elliptic flow increases by about 30%. Some hydrodynamic model predictions which include viscous corrections are in agreement with the observed increase.Comment: 10 pages, 4 captioned figures, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/389

Suppression of charged particle production at large transverse momentum in central Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV

Inclusive transverse momentum spectra of primary charged particles in Pb-Pb collisions at $\sqrt{s_{_{\rm NN}}}$ = 2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0-5% and 70-80% of the hadronic Pb-Pb cross section. The measured charged particle spectra in $|\eta|<0.8$ and $0.3 < p_T < 20$ GeV/$c$ are compared to the expectation in pp collisions at the same $\sqrt{s_{\rm NN}}$, scaled by the number of underlying nucleon-nucleon collisions. The comparison is expressed in terms of the nuclear modification factor $R_{\rm AA}$. The result indicates only weak medium effects ($R_{\rm AA} \approx$ 0.7) in peripheral collisions. In central collisions, $R_{\rm AA}$ reaches a minimum of about 0.14 at $p_{\rm T}=6$-7GeV/$c$ and increases significantly at larger $p_{\rm T}$. The measured suppression of high-$p_{\rm T}$ particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb-Pb collisions at the LHC.Comment: 15 pages, 5 captioned figures, 3 tables, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/98

Two-pion Bose-Einstein correlations in central Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/388

CD4+ Regulatory and Effector/Memory T Cell Subsets Profile Motor Dysfunction in Parkinson’s Disease

Animal models and clinical studies have linked the innate and adaptive immune system to the pathology of Parkinson’s disease (PD). Despite such progress, the specific immune responses that influence disease progression have eluded investigators. Herein, we assessed relationships between T cell phenotype and function with PD progression. Peripheral blood lymphocytes from two separate cohorts, a discovery cohort and a validation cohort, totaling 113 PD patients and 96 age- and environment-matched caregivers were examined by flow cytometric analysis and T cell proliferation assays. Increased effector/memory T cells (Tem), defined as CD45RO+ and FAS+ CD4+ T cells and decreased CD31+ and α4β7+ CD4+ T cells were associated with progressive Unified Parkinson’s Disease Rating Scale III scores. However, no associations were seen between immune biomarkers and increased age or disease duration. Impaired abilities of regulatory T cells (Treg) from PD patients to suppress effector T cell function was observed. These data support the concept that chronic immune stimulation, notably Tem activation and Treg dysfunction is linked to PD pathobiology and disease severity, but not disease duration. The association of T cell phenotypes with motor symptoms provides fresh avenues for novel biomarkers and therapeutic designs

The complete genome sequence of Corynebacterium pseudotuberculosis FRC41 isolated from a 12-year-old girl with necrotizing lymphadenitis reveals insights into gene-regulatory networks contributing to virulence

Trost E, Ott L, Schneider J, et al. The complete genome sequence of Corynebacterium pseudotuberculosis FRC41 isolated from a 12-year-old girl with necrotizing lymphadenitis reveals insights into gene-regulatory networks contributing to virulence. BMC Genomics. 2010;11(1): 728

Measurement of event background fluctuations for charged particle jet reconstruction in Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV

The effect of event background fluctuations on charged particle jet reconstruction in Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV has been measured with the ALICE experiment. The main sources of non-statistical fluctuations are characterized based purely on experimental data with an unbiased method, as well as by using single high $p_{\rm T}$ particles and simulated jets embedded into real Pb-Pb events and reconstructed with the anti-$k_{\rm T}$ jet finder. The influence of a low transverse momentum cut-off on particles used in the jet reconstruction is quantified by varying the minimum track $p_{\rm T}$ between 0.15 GeV/$c$ and 2 GeV/$c$. For embedded jets reconstructed from charged particles with $p_{\rm T} > 0.15$ GeV/$c$, the uncertainty in the reconstructed jet transverse momentum due to the heavy-ion background is measured to be 11.3 GeV/$c$ (standard deviation) for the 10% most central Pb-Pb collisions, slightly larger than the value of 11.0 GeV/$c$ measured using the unbiased method. For a higher particle transverse momentum threshold of 2 GeV/$c$, which will generate a stronger bias towards hard fragmentation in the jet finding process, the standard deviation of the fluctuations in the reconstructed jet transverse momentum is reduced to 4.8-5.0 GeV/$c$ for the 10% most central events. A non-Gaussian tail of the momentum uncertainty is observed and its impact on the reconstructed jet spectrum is evaluated for varying particle momentum thresholds, by folding the measured fluctuations with steeply falling spectra.Comment: 21 pages, 5 captioned figures, 3 tables, authors from page 16, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/350

GWAS of Suicide Attempt in Psychiatric Disorders Identifies Association With Major Depression Polygenic Risk Scores

Objective: Over 90% of suicide attempters have a psychiatric diagnosis, however twin and family studies suggest that the genetic etiology of suicide attempt (SA) is partially distinct from that of the psychiatric disorders themselves. Here, we present the largest genome-wide association study (GWAS) on suicide attempt using major depressive disorder (MDD), bipolar disorder (BIP) and schizophrenia (SCZ) cohorts from the Psychiatric Genomics Consortium. Method: Samples comprise 1622 suicide attempters and 8786 non-attempters with MDD, 3264 attempters and 5500 non-attempters with BIP and 1683 attempters and 2946 non-attempters with SCZ. SA GWAS were performed by comparing attempters to non-attempters in each disorder followed by meta-analyses across disorders. Polygenic risk scoring was used to investigate the genetic relationship between SA and the psychiatric disorders. Results: Three genome-wide significant loci for SA were found: one associated with SA in MDD, one in BIP, and one in the meta-analysis of SA in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with SA in MDD (R2=0.25%, P=0.0006), BIP (R2=0.24%, P=0.0002) and SCZ (R2=0.40%, P=0.0006). Conclusions: This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size hold potential to robustly identify genetic associations and gain biological insights into the etiology of suicide attempt

Neutral pion and η\eta meson production in proton-proton collisions at s=0.9\sqrt{s}=0.9 TeV and s=7\sqrt{s}=7 TeV

The first measurements of the invariant differential cross sections of inclusive $\pi^0$ and $\eta$ meson production at mid-rapidity in proton-proton collisions at $\sqrt{s}=0.9$ TeV and $\sqrt{s}=7$ TeV are reported. The $\pi^0$ measurement covers the ranges $0.4<p_T<7$ GeV/$c$ and $0.3<p_T<25$ GeV/$c$ for these two energies, respectively. The production of $\eta$ mesons was measured at $\sqrt{s}=7$ TeV in the range $0.4<p_T<15$ GeV/$c$. Next-to-Leading Order perturbative QCD calculations, which are consistent with the $\pi^0$ spectrum at $\sqrt{s}=0.9$ TeV, overestimate those of $\pi^0$ and $\eta$ mesons at $\sqrt{s}=7$ TeV, but agree with the measured $\eta/\pi^0$ ratio at $\sqrt{s}=7$ TeV.Comment: 17 pages, 5 captioned figures, 2 tables, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/310