Cryogenic Gaseous Photomultiplier for position reconstruction of liquid argon scintillation light

Presented here are first tests of a Gaseous Photomultiplier based on a cascade of Thick GEM structures intended for gamma-ray position reconstruction in liquid argon. The detector has a MgF2 window, transparent to VUV light, and a CsI photocathode deposited on the first THGEM . A gain of 8⋅ 105 per photoelectron and ~ 100% photoelectron collection efficiency are measured at stable operation settings. The excellent position resolution capabilities of the detector (better than 100 μm) at 100 kHz readout rate, is demonstrated at room temperature. Structural integrity tests of the detector and seals are successfully performed at cryogenic temperatures by immersing the detector in liquid Nitrogen, laying a good foundation for future operation tests in noble liquids

Neuroimmunomodulatory and neuroprotective effects of the flavonoid apigenin in in vitro models of neuroinflammation associated with Alzheimer's disease

Neurodegenerative disorders (ND) are characterized by the progressive and irreversible loss of neurons. Alzheimer’s Disease (AD) is the most incident age-related ND, in which the presence of a chronic inflammatory compound seems to be related to its pathogenesis. Different stimuli in the central nervous system (CNS) can induce activation, proliferation, and changes in phenotype and glial function, which can be modulated by anti-inflammatory agents. Apigenin (4,5,7–trihydroxyflavone) is a flavonoid found in abundance in many fruits and vegetables, that has shown important effects upon controlling the inflammatory response. This study evaluated the neuroprotective and neuroimmunomodulatory potential of apigenin using in vitro models of neuroinflammation associated with AD. Co-cultures of neurons and glial cells were obtained from the cortex of newborn and embryonic Wistar rats. After 26 days in vitro, cultures were exposed to lipopolysaccharide (LPS; 1 μg/ml), or IL-1β (10 ng/ml) for 24 h, or to Aβ oligomers (500 nM) for 4 h, and then treated with apigenin (1 μM) for further 24 h. It was observed that the treatment with apigenin preserved neurons and astrocytes integrity, determined by Rosenfeld’s staining and immunocytochemistry for β-tubulin III and GFAP, respectively. Moreover, it was observed by Fluoro-Jade-B and caspase-3 immunostaining that apigenin was not neurotoxic and has a neuroprotective effect against inflammatory damage. Additionally, apigenin reduced microglial activation, characterized by inhibition of proliferation (BrdU+ cells) and modulation of microglia morphology (Iba-1 + cells), and decreased the expression of the M1 inflammatory marker CD68. Moreover, as determined by RT-qPCR, inflammatory stimuli induced by IL-1β increased the mRNA expression of IL-6, IL-1β, and CCL5, and decreased the mRNA expression of IL-10. Contrary, after treatment with apigenin in inflammatory stimuli (IL-1β or LPS) there was a modulation of the mRNA expression of inflammatory cytokines, and reduced expression of OX42, IL-6 and gp130. Moreover, apigenin alone and after an inflammatory stimulus with IL-1β also induced the increase in the expression of brain-derived neurotrophic factor (BDNF), an effect that may be associated with anti-inflammatory and neuroprotective effects. Together these data demonstrate that apigenin presents neuroprotective and anti-inflammatory effects in vitro and might represent an important neuroimmunomodulatory agent for the treatment of neurodegenerative conditions

Função energia generalizada de controle para estabilização de sistemas não lineares

Neste trabalho, o conceito de função de Lyapunov de controle é estendido em duas direções principais. Na primeira direção, o conceito de função energia de controle (FEC) é proposto com o objetivo de não somente projetar leis de controle estabilizantes para sistemas não lineares mas também com o objetivo de fornecer uma estimativa da região de estabilidade do sistema em malha fechada. A FLC garante estabilidade local de um certo ponto de equilíbrio do sistema em malha fechada, mas usualmente não fornece estimativasótimas da região de estabilidade. O conceito de FEC é mais exigente que o conceito de FLC. Além de garantir estabilidade local do equilíbrio, a FEC fornece informações globais a respeito dos conjuntos limites e estimativas ótimas das regiões de estabilidade. A segunda direção está relacionada com o fato de que, em geral, é difícil encontrar FLC ou FEC para muitos sistemas não lineares. De forma a minimizar este problema e aplicar õ conceito de CEF em uma classe maior de sistemas, propõe-se neste artigo o conceito de função energia generalizada de controle (FEGC). A FEGC permite o projeto de controladores mesmo quando a derivada da função energia é positiva em algumas regiões limitadas do espaço de estados.extended in two main directions. In the first direction, the concept of control energy function (CEF) is proposed not only to design stabilizing feedback control laws but also to provide an estimate of the stability region of the closed-loopsystem. The CLF guarantees local stability of the closedloop- system but usually cannot provide optimal estimates of its stability region. The CEF concept is more restrict than the CLF concept. Beyond the guarantee of local stability, the CEF provides global information about limit sets and optimal estimates of stability region. The second direction is related to the fact that, in general, it is difficult to find a CLF or a CEF for many nonlinear systems. In order to overcome this problem and apply the concept of CEF for a larger class of systems, the concept of generalized control energy function (GCEF) is proposed in this paper. The GCEF allows the design of nonlinear controllers even when the derivative of the energy function is positive in some bounded regions of the state space

ER stress activation in the intestinal mucosa but not in mesenteric adipose tissue is associated with inflammation in Crohn’s disease patients

Chronic/abnormal activation of endoplasmic reticulum (ER) stress is linked to the exacerbation of the inflammatory process and has been recently linked to Crohn’s disease (CD) pathophysiology. We investigated the intestinal mucosa and the mesenteric adipose tissue (MAT) collected from CD patients with active disease (CD group) and from non-IBD patients (CTR group) to study ER stress activation and to address tissue-specific modulation in CD. The intestinal mucosa of CD patients showed an upregulation in the expression of ER stress related genes, including ATF3, DNAJC3, STC2, DDIT3, CALR, HSPA5 and HSP90B1. Results showed that EIF2AK3 gene was upregulated, along with increased protein expression of p-eIF2α and p-eIF2α/eIF2α ratio. Additionally, ERN1 gene expression was upregulated, along with an increased spliced/activated form sXBP1 protein. Despite the upregulation of ATF6 gene expression in the intestinal mucosa of CD patients, no differences were found in ATF6 protein expression. Lastly, the analysis of MAT revealed unchanged levels of ER stress markers along with no differences in the activation of UPR. However, chaperone gene expression was modulated in the MAT of CD patients. To conclude, our results address tissue-specific differences in UPR activation in CD and point the ER stress as an important pro-inflammatory mechanism in CD, specifically in the intestinal mucosa149CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP401270/2016-502-P-28707/20122016/01638-

Role of zika virus envelope protein domain iii as a target of human neutralizing antibodies

Zika virus (ZIKV) is a flavivirus that is structurally highly similar to the related viruses, dengue virus (DENV), West Nile virus, and yellow fever virus. ZIKV causes an acute infection that often results in mild symptoms but that can cause severe disease in rare instances. Following infection, individuals mount an adaptive immune response, composed of antibodies (Abs) that target the envelope (E) glycoprotein of ZIKV, which covers the surface of the virus. Groups have studied monoclonal antibodies and polyclonal immune sera isolated from individuals who recovered from natural ZIKV infections. Some of these antibodies bind to domain III of E (EDIII), but the functional importance of these antibodies is unknown. In this study, we aimed to determine if EDIII is a major target of the potent serum neutralizing antibodies present in people after ZIKV infection. By generating a chimeric virus containing ZIKV EDIII in a DENV4 virus backbone, our data show a minor role of EDIIItargeting antibodies in human polyclonal neutralization. These results reveal that while monoclonal antibody (MAb) studies are informative in identifying individual antibody epitopes, they can overestimate the importance of epitopes contained within EDIII as targets of serum neutralizing antibodies. Additionally, these results argue that the major target of human ZIKV neutralizing antibodies resides elsewhere in E; however, further studies are needed to assess the epitope specificity of the neutralizing response at the population level. Identification of the major epitopes on the envelope of ZIKV recognized by serum neutralizing antibodies is critical for understanding protective immunity following natural infection and for guiding the design and evaluation of vaccines. IMPORTANCE Zika virus is a flavivirus that was recently introduced to Latin America, where it caused a massive epidemic. Individuals infected with ZIKV generate an immune response composed of antibodies which bind to the envelope (E) protein. These anti-E antibodies are critical in protecting individuals from subsequent infection. Multiple groups have found that many ZIKV antibodies bind to domain III of E (EDIII), suggesting that this region is an important target of neutralizing antibodies. Here, we generated a chimeric virus containing ZIKV EDIII in a dengue virus backbone to measure ZIKV EDIIIspecific antibody responses. We found that while polyclonal ZIKV immune serum contains antibodies targeting EDIII, they constitute only a small fraction of the total population of antibodies that neutralize ZIKV. Further studies are needed to define the main targets on the viral envelope recognized by human neutralizing antibodies, which is critical for guiding the development of ZIKV vaccines

Adiabatic perturbation theory: from Landau-Zener problem to quenching through a quantum critical point

We discuss the application of the adiabatic perturbation theory to analyze the dynamics in various systems in the limit of slow parametric changes of the Hamiltonian. We first consider a two-level system and give an elementary derivation of the asymptotics of the transition probability when the tuning parameter slowly changes in the finite range. Then we apply this perturbation theory to many-particle systems with low energy spectrum characterized by quasiparticle excitations. Within this approach we derive the scaling of various quantities such as the density of generated defects, entropy and energy. We discuss the applications of this approach to a specific situation where the system crosses a quantum critical point. We also show the connection between adiabatic and sudden quenches near a quantum phase transitions and discuss the effects of quasiparticle statistics on slow and sudden quenches at finite temperatures.Comment: 20 pages, 3 figures, contribution to "Quantum Quenching, Annealing and Computation", Eds. A. Das, A. Chandra and B. K. Chakrabarti, Lect. Notes in Phys., Springer, Heidelberg (2009, to be published), reference correcte

Constraints on Dark Matter Annihilation in Clusters of Galaxies with the Fermi Large Area Telescope

Nearby clusters and groups of galaxies are potentially bright sources of high-energy gamma-ray emission resulting from the pair-annihilation of dark matter particles. However, no significant gamma-ray emission has been detected so far from clusters in the first 11 months of observations with the Fermi Large Area Telescope. We interpret this non-detection in terms of constraints on dark matter particle properties. In particular for leptonic annihilation final states and particle masses greater than ~200 GeV, gamma-ray emission from inverse Compton scattering of CMB photons is expected to dominate the dark matter annihilation signal from clusters, and our gamma-ray limits exclude large regions of the parameter space that would give a good fit to the recent anomalous Pamela and Fermi-LAT electron-positron measurements. We also present constraints on the annihilation of more standard dark matter candidates, such as the lightest neutralino of supersymmetric models. The constraints are particularly strong when including the fact that clusters are known to contain substructure at least on galaxy scales, increasing the expected gamma-ray flux by a factor of ~5 over a smooth-halo assumption. We also explore the effect of uncertainties in cluster dark matter density profiles, finding a systematic uncertainty in the constraints of roughly a factor of two, but similar overall conclusions. In this work, we focus on deriving limits on dark matter models; a more general consideration of the Fermi-LAT data on clusters and clusters as gamma-ray sources is forthcoming.Comment: accepted to JCAP, Corresponding authors: T.E. Jeltema and S. Profumo, minor revisions to be consistent with accepted versio