Function inferences from a molecular structural model of bacterial ParE toxin

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Differential cross section measurements for the production of a W boson in association with jets in proton-proton collisions at √s=7 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Measurements of jet multiplicity and differential production cross sections of Z plus jets events in proton-proton collisions at root s=7 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Measurement of J/ψ and ψ(2S) Prompt Double-Differential Cross Sections in pp Collisions at s√=7 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Measurement of the inclusive 3-jet production differential cross section in proton-proton collisions at 7 TeV and determination of the strong coupling constant in the TeV range

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Measurement of differential cross sections for the production of a pair of isolated photons in pp collisions at root s=7TeV

A measurement of differential cross sections for the production of a pair of isolated photons in proton-proton collisions at root s = 7 TeV is presented. The data sample corresponds to an integrated luminosity of 5.0 fb(-1) collected with the CMS detector. A data-driven isolation template method is used to extract the prompt diphoton yield. The measured cross section for two isolated photons, with transverse energy above 40 and 25 GeV respectively, in the pseudorapidity range vertical bar eta vertical bar < 2.5, vertical bar eta vertical bar (sic) [1.44, 1.57] and with an angular separation Delta R > 0.45, is 17.2 +/-0.2 (stat) +/-1.9 (syst) +/- 0.4 (lumi) pb. Differential cross sections are measured as a function of the diphoton invariant mass, the diphoton transverse momentum, the azimuthal angle difference between the two photons, and the cosine of the polar angle in the Collins-Soper reference frame of the diphoton system. The results are compared to theoretical predictions at leading, next-to-leading, and next-to-next-to-leading order in quantum chromodynamics.

Tradução para o português brasileiro, adaptação transcultural e validação do 3D Assessment of Hand Function

Pós-graduação em Bases Gerais da Cirurgia - FMB

Differential calculus and integration of generalized functions over membranes

In this paper we continue the development of the differential calculus started in Aragona et al. (Monatsh. Math. 144: 13-29, 2005). Guided by the so-called sharp topology and the interpretation of Colombeau generalized functions as point functions on generalized point sets, we introduce the notion of membranes and extend the definition of integrals, given in Aragona et al. (Monatsh. Math. 144: 13-29, 2005), to integrals defined on membranes. We use this to prove a generalized version of the Cauchy formula and to obtain the Goursat Theorem for generalized holomorphic functions. A number of results from classical differential and integral calculus, like the inverse and implicit function theorems and Green's theorem, are transferred to the generalized setting. Further, we indicate that solution formulas for transport and wave equations with generalized initial data can be obtained as well.

Plasma cortisol in first episode drug-naive mania: Differential levels in euphoric versus irritable mood

Background: Dysregulation of HPA axis has been widely described in subjects with bipolar disorder (BD), including changes in cortisol levels during mood episodes and euthymia. However, most of the studies were done with medicated BD patients with variable length of illness, which was shown to interfere on peripheral cortisol levels. Therefore, the present study aims to evaluate plasma cortisol levels in drug-naive BD subjects during the first manic episode, as well as investigate the relationship between plasma cortisol levels and manic symptomatology. Methods: Twenty-six drug-naive patients were enrolled meeting criteria for a first manic episode in bipolar I disorder. Severity of mania was assessed using the Young Mania Rating Scale (YMRS). The control group included 27 healthy subjects matched by age and gender. Cortisol was quantified using a direct radioimmunoassay. Results: Plasma cortisol levels were decreased during first manic episode compared to healthy controls. Higher cortisol levels were positively associated with the presence of irritability (dysphoria), while elated mania showed lower cortisol levels compared to controls. Limitation: Data including larger samples are lacking. Conclusion: Higher cortisol in dysphoric mania compared to predominantly elated/euphoric mania may indicate a clinical and neurobiological polymorphic phenomenon, potentially involving a higher biological sensitivity to stress in the presence of irritable mood. The present findings highlight the importance to add a dimensional approach to the traditional categorical diagnosis for future neurobiological studies in BD. (C) 2011 Elsevier B.V. All rights reserved.

Investigating Smart Sampling as a population initialization method for Differential Evolution in continuous problems

Recently, researches have shown that the performance of metaheuristics can be affected by population initialization. Opposition-based Differential Evolution (ODE), Quasi-Oppositional Differential Evolution (QODE), and Uniform-Quasi-Opposition Differential Evolution (UQODE) are three state-of-the-art methods that improve the performance of the Differential Evolution algorithm based on population initialization and different search strategies. In a different approach to achieve similar results, this paper presents a technique to discover promising regions in a continuous search-space of an optimization problem. Using machine-learning techniques, the algorithm named Smart Sampling (SS) finds regions with high possibility of containing a global optimum. Next, a metaheuristic can be initialized inside each region to find that optimum. SS and DE were combined (originating the SSDE algorithm) to evaluate our approach, and experiments were conducted in the same set of benchmark functions used by ODE, QODE and UQODE authors. Results have shown that the total number of function evaluations required by DE to reach the global optimum can be significantly reduced and that the success rate improves if SS is employed first. Such results are also in consonance with results from the literature, stating the importance of an adequate starting population. Moreover, SS presents better efficacy to find initial populations of superior quality when compared to the other three algorithms that employ oppositional learning. Finally and most important, the SS performance in finding promising regions is independent of the employed metaheuristic with which SS is combined, making SS suitable to improve the performance of a large variety of optimization techniques. (C) 2012 Elsevier Inc. All rights reserved.

Melatonin reduces LH, 17 beta-estradiol and induces differential regulation of sex steroid receptors in reproductive tissues during rat ovulation

Abstract Background Melatonin is associated with direct or indirect actions upon female reproductive function. However, its effects on sex hormones and steroid receptors during ovulation are not clearly defined. This study aimed to verify whether exposure to long-term melatonin is able to cause reproductive hormonal disturbances as well as their role on sex steroid receptors in the rat ovary, oviduct and uterus during ovulation. Methods Twenty-four adult Wistar rats, 60 days old (+/- 250 g) were randomly divided into two groups. Control group (Co): received 0.9% NaCl 0.3 mL + 95% ethanol 0.04 mL as vehicle; Melatonin-treated group (MEL): received vehicle + melatonin [100 μg/100 g BW/day] both intraperitoneally during 60 days. All animals were euthanized by decapitation during the morning estrus at 4 a.m. Results Melatonin significantly reduced the plasma levels of LH and 17 beta-estradiol, while urinary 6-sulfatoximelatonin (STM) was increased at the morning estrus. In addition, melatonin promoted differential regulation of the estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR) and melatonin receptor (MTR) along the reproductive tissues. In ovary, melatonin induced a down-regulation of ER-alpha and PRB levels. Conversely, it was observed that PRA and MT1R were up-regulated. In oviduct, AR and ER-alpha levels were down-regulated, in contrast to high expression of both PRA and PRB. Finally, the ER-beta and PRB levels were down-regulated in uterus tissue and only MT1R was up-regulated. Conclusions We suggest that melatonin partially suppress the hypothalamus-pituitary-ovarian axis, in addition, it induces differential regulation of sex steroid receptors in the ovary, oviduct and uterus during ovulation.

Differential effects of task-specific practice on performance in a simulated penalty kick under high-pressure

Objectives The current study investigated to what extent task-specific practice can help reduce the adverse effects of high-pressure on performance in a simulated penalty kick task. Based on the assumption that practice attenuates the required attentional resources, it was hypothesized that task-specific practice would enhance resilience against high-pressure. Method Participants practiced a simulated penalty kick in which they had to move a lever to the side opposite to the goalkeeper's dive. The goalkeeper moved at different times before ball-contact. Design Before and after task-specific practice, participants were tested on the same task both under low- and high-pressure conditions. Results Before practice, performance of all participants worsened under high-pressure; however, whereas one group of participants merely required more time to correctly respond to the goalkeeper movement and showed a typical logistic relation between the percentage of correct responses and the time available to respond, a second group of participants showed a linear relationship between the percentage of correct responses and the time available to respond. This implies that they tended to make systematic errors for the shortest times available. Practice eliminated the debilitating effects of high-pressure in the former group, whereas in the latter group high-pressure continued to negatively affect performance. Conclusions Task-specific practice increased resilience to high-pressure. However, the effect was a function of how participants responded initially to high-pressure, that is, prior to practice. The results are discussed within the framework of attentional control theory (ACT).

Differential cell type-specific transcriptional regulation of the CYP1A1 gene

Cytochrome P450 1A1 (CYP1A1) monooxygenase plays an important role in the metabolism of environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs) and halogenated polycyclic aromatic hydrocarbons (HAHs). Oxidation of these compounds converts them to the metabolites that subsequently can be conjugated to hydrophilic endogenous entities e.g. glutathione. Derivates generated in this way are water soluble and can be excreted in bile or urine, which is a defense mechanism. Besides detoxification, metabolism by CYP1A1 may lead to deleterious effects since the highly reactive intermediate metabolites are able to react with DNA and thus cause mutagenic effects, as it is in the case of benzo(a) pyrene (B[a]P). CYP1A1 is normally not expressed or expressed at a very low level in the cells but it is inducible by many PAHs and HAHs e.g. by B[a]P or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Transcriptional activation of the CYP1A1 gene is mediated by aryl hydrocarbon receptor (AHR), a basic-helix-loop-helix (bHLH) transcription factor. In the absence of a ligand AHR stays predominantly in the cytoplasm. Ligand binding causes translocation of AHR to the nuclear compartment, its heterodimerization with another bHLH protein, the aryl hydrocarbon nuclear translocator (ARNT) and binding of the AHR/ARNT heterodimer to a DNA motif designated dioxin responsive element (DRE). This process leads to the transcriptional activation of the responsive genes containing DREs in their regulatory regions, e.g. that coding for CYP1A1. TCDD is the most potent known agonist of AHR. Since it is not metabolized by the activated enzymes, exposure to this compound leads to a persisting activation of AHR resulting in diverse toxic effects in the organism. To enlighten the molecular mechanisms that mediate the toxicity of xenobiotics like TCDD and related compounds, the AHR-dependent regulation of the CYP1A1 gene was investigated in two cell lines: human cervix carcinoma (HeLa) and mouse hepatoma (Hepa). Study of AHR activation and its consequence concerning expression of the CYP1A1 enzyme confirmed the TCDD-dependent formation of the AHR/ARNT complex on DRE leading to an increase of the CYP1A1 transcription in Hepa cells. In contrast, in HeLa cells formation of the AHR/ARNT heterodimer and binding of a protein complex containing AHR and ARNT to DRE occurred naturally in the absence of TCDD. Moreover, treatment with TCDD did not affect the AHR/ARNT dimer formation and binding of these proteins to DRE in these cells. Even though the constitutive complex on DRE exists in HeLa, transcription of the CYP1A1 gene was not increased. Furthermore, the CYP1A1 level in HeLa cells remained unchanged in the presence of TCDD suggesting repressional mechanism of the AHR complex function which may hinder the TCDD-dependent mechanisms in these cells. Similar to the native, the mouse CYP1A1-driven reporter constructs containing different regulatory elements were not inducible by TCDD in HeLa cells, which supported a presence of cell type specific trans-acting factor in HeLa cells able to repress both the native CYP1A1 and CYP1A1-driven reporter genes rather than species specific differences between CYP1A1 genes of human and rodent origin. The different regulation of the AHR-mediated transcription of CYP1A1 gene in Hepa and HeLa cells was further explored in order to elucidate two aspects of the AHR function: (I) mechanism involved in the activation of AHR in the absence of exogenous ligand and (II) factor that repress function of the exogenous ligand-independent AHR/ARNT complex. Since preliminary studies revealed that the activation of PKA causes an activation of AHR in Hepa cells in the absence of TCDD, the PKA-dependent signalling pathway was the proposed endogenous mechanism leading to the TCDD-independent activation of AHR in HeLa cells. Activation of PKA by forskolin or db-cAMP as well as inhibition of the kinase by H89 in both HeLa and Hepa cells did not lead to alterations in the AHR interaction with ARNT in the absence of TCDD and had no effect on binding of these proteins to DRE. Moreover, the modulators of PKA did not influence the CYP1A1 activity in these cells in the presence and in the absence of TCDD. Thus, an involvement of PKA in the regulation of the CYP1A1 Gen in HeLa cells was not evaluated in the course of this study. Repression of genes by transcription factors bound to their responsive elements in the absence of ligands has been described for nuclear receptors. These receptors interact with protein complex containing histone deacetylase (HDAC), enzyme responsible for the repressional effect. Thus, a participation of histone deacetylase in the transcriptional modulation of CYP1A1 gene by the constitutively DNA-bound AHR/ARNT complex was supposed. Inhibition of the HDAC activity by trichostatin A (TSA) or sodium butyrate (NaBu) led to an increase of the CYP1A1 transcription in the presence but not in the absence of TCDD in Hepa and HeLa cells. Since amount of the AHR and ARNT proteins remained unchanged upon treatment of the cells with TSA or NaBu, the transcriptional upregulation of CYP1A1 gene was not due to an increased expression of the regulatory proteins. These findings strongly suggest an involvement of HDAC in the repression of the CYP1A1 gene. Similar to the native human CYP1A1 also the mouse CYP1A1-driven reporter gene transfected into HeLa cells was repressed by histone deacetylase since the presence of TSA or NaBu led to an increase in the reporter activity. Induction of reporter gene did not require a presence of the promoter or negative regulatory regions of the CYP1A1 gene. A promoter-distal fragment containing three DREs together with surrounding sequences was sufficient to mediate the effects of the HDAC inhibitors suggesting that the AHR/ARNT binding to its specific DNA recognition site may be important for the CYP1A1 repression. Histone deacetylase is recruited to the specific genes by corepressors, proteins that bind to the transcription factors and interact with other members of the HDAC complex. Western blot analyses revealed a presence of HDAC1 and the corepressors mSin3A (mammalian homolog of yeast Sin3) and SMRT (silencing mediator for retinoid and thyroid hormone receptor) in both cell types, while the corepressor NCoR (nuclear receptor corepressor) was expressed exclusively in HeLa cells. Thus the high inducibility of CYP1A1 in Hepa cells may be due to the absence of NCoR in these cells in contrast to the non-responsive HeLa cells, where the presence of NCoR would support repression of the gene by histone deacetylase. This hypothesis was verified in reporter gene experiments where expression constructs coding for the particular members of the HDAC complex were cotransfected in Hepa cells together with the TCDD-inducible reporter constructs containing the CYP1A1 regulatory sequences. An overexpression of NCoR however did not decrease but instead led to a slight increase of the reporter gene activity in the cells. The expected inhibition was observed solely in the case of SMRT that slightly reduced constitutive and TCDD-induced reporter gene activity. A simultaneous expression of NCoR and SMRT shown no further effects and coexpression of HDAC1 with the two corepressors did not alter this situation. Thus, additional factors that are likely involved in the repression of CYP1A1 gene by HDAC complex remained to be identified. Taking together, characterisation of an exogenous ligand independent AHR/ARNT complex on DRE in HeLa cells that repress transcription of the CYP1A1 gene creates a model system enabling investigation of endogenous processes involved in the regulation of AHR function. This study implicates HDAC-mediated repression of CYP1A1 gene that contributes to the xenobiotic-induced expression in a tissue specific manner. Elucidation of these processes gains an insight into mechanisms leading to deleterious effects of TCDD and related compounds.

Measurement of the differential cross section of tt pairs in pp collision at sqrt(s) = 7TeV with the ATLAS detector at the LHC

In this thesis three measurements of top-antitop differential cross section at an energy in the center of mass of 7 TeV will be shown, as a function of the transverse momentum, the mass and the rapidity of the top-antitop system. The analysis has been carried over a data sample of about 5/fb recorded with the ATLAS detector. The events have been selected with a cut based approach in the "one lepton plus jets" channel, where the lepton can be either an electron or a muon. The most relevant backgrounds (multi-jet QCD and W+jets) have been extracted using data driven methods; the others (Z+ jets, diboson and single top) have been simulated with Monte Carlo techniques. The final, background-subtracted, distributions have been corrected, using unfolding methods, for the detector and selection effects. At the end, the results have been compared with the theoretical predictions. The measurements are dominated by the systematic uncertainties and show no relevant deviation from the Standard Model predictions.

Generalized Differential Quadrature Finite Element Method applied to Advanced Structural Mechanics

Over the years the Differential Quadrature (DQ) method has distinguished because of its high accuracy, straightforward implementation and general ap- plication to a variety of problems. There has been an increase in this topic by several researchers who experienced significant development in the last years. DQ is essentially a generalization of the popular Gaussian Quadrature (GQ) used for numerical integration functions. GQ approximates a finite in- tegral as a weighted sum of integrand values at selected points in a problem domain whereas DQ approximate the derivatives of a smooth function at a point as a weighted sum of function values at selected nodes. A direct appli- cation of this elegant methodology is to solve ordinary and partial differential equations. Furthermore in recent years the DQ formulation has been gener- alized in the weighting coefficients computations to let the approach to be more flexible and accurate. As a result it has been indicated as Generalized Differential Quadrature (GDQ) method. However the applicability of GDQ in its original form is still limited. It has been proven to fail for problems with strong material discontinuities as well as problems involving singularities and irregularities. On the other hand the very well-known Finite Element (FE) method could overcome these issues because it subdivides the computational domain into a certain number of elements in which the solution is calculated. Recently, some researchers have been studying a numerical technique which could use the advantages of the GDQ method and the advantages of FE method. This methodology has got different names among each research group, it will be indicated here as Generalized Differential Quadrature Finite Element Method (GDQFEM).