Impact-parameter dependent nuclear parton distribution functions: EPS09s and EKS98s and their applications in nuclear hard processes

We determine the spatial (impact parameter) dependence of nuclear parton distribution functions (nPDFs) using the $A$-dependence of the spatially independent (averaged) global fits EPS09 and EKS98. We work under the assumption that the spatial dependence can be formulated as a power series of the nuclear thickness functions $T_A$. To reproduce the $A$-dependence over the entire $x$ range we need terms up to $[T_A]^4$. As an outcome, we release two sets, EPS09s (LO, NLO, error sets) and EKS98s, of spatially dependent nPDFs for public use. We also discuss the implementation of these into the existing calculations. With our results, the centrality dependence of nuclear hard-process observables can be studied consistently with the globally fitted nPDFs for the first time. As an application, we first calculate the LO nuclear modification factor $R^{1jet}_{AA}$ for primary partonic-jet production in different centrality classes in Au+Au collisions at RHIC and Pb+Pb collisions at LHC. Also the corresponding central-to-peripheral ratios $R_{CP}^{1jet}$ are studied. We also calculate the LO and NLO nuclear modification factors for single inclusive neutral pion production, $R_{dAu}^{\pi^0}$, at mid- and forward rapidities in different centrality classes in d+Au collisions at RHIC. In particular, we show that our results are compatible with the PHENIX mid-rapidity data within the overall normalization uncertainties given by the experiment. Finally, we show our predictions for the corresponding modifications $R_{pPb}^{\pi^0}$ in the forthcoming p+Pb collisions at LHC.Comment: 36 page

Personality disorders and psychosocial problems in a group of participants to therapeutic processes for people with severe social disabilities

<p>Abstract</p> <p>Background</p> <p>Homeless people have high dropout rates when they participate in therapeutic processes. The causes of this failure are not always known. This study investigates whether dropping-out is mediated by personality disorders or whether psychosocial problems are more important.</p> <p>Method</p> <p>Eighty-nine homeless people in a socio-laboral integration process were assessed. An initial interview was used, and the MCMI II questionnaire was applied to investigate the presence of psychosocial disorders (DSM-IV-TR axis IV). This was designed as an <it>ex post-facto </it>prospective study.</p> <p>Results</p> <p>Personality disorders were very frequent among the homeless people examined. Moreover, the high index of psychosocial problems (axis IV) in this population supported the proposal that axis IV disorders are influential in failure to complete therapy.</p> <p>Conclusion</p> <p>The outcomes of the study show that the homeless people examined presented with more psychopathological symptoms, in both axis II and axis IV, than the general population. This supports the need to take into account the comorbidity between these two types of disorder among homeless people, in treatment and in the development of specific intervention programs. In conclusion, the need for more psychosocial treatments addressing the individual problems of homeless people is supported.</p

Brief wide-field photostimuli evoke and modulate oscillatory reverberating activity in cortical networks

Cell assemblies manipulation by optogenetics is pivotal to advance neuroscience and neuroengineering. In in vivo applications, photostimulation often broadly addresses a population of cells simultaneously, leading to feed-forward and to reverberating responses in recurrent microcircuits. The former arise from direct activation of targets downstream, and are straightforward to interpret. The latter are consequence of feedback connectivity and may reflect a variety of time-scales and complex dynamical properties. We investigated wide-field photostimulation in cortical networks in vitro, employing substrate-integrated microelectrode arrays and long-term cultured neuronal networks. We characterized the effect of brief light pulses, while restricting the expression of channelrhodopsin to principal neurons. We evoked robust reverberating responses, oscillating in the physiological gamma frequency range, and found that such a frequency could be reliably manipulated varying the light pulse duration, not its intensity. By pharmacology, mathematical modelling, and intracellular recordings, we conclude that gamma oscillations likely emerge as in vivo from the excitatory-inhibitory interplay and that, unexpectedly, the light stimuli transiently facilitate excitatory synaptic transmission. Of relevance for in vitro models of (dys)functional cortical microcircuitry and in vivo manipulations of cell assemblies, we give for the first time evidence of network-level consequences of the alteration of synaptic physiology by optogenetics

An investigation of the phase locking index for measuring of interdependency of cortical source signals recorded in the EEG

The phase locking index (PLI) was introduced to quantify in a statistical sense the phase synchronization of two signals. It has been commonly used to process biosignals. In this article, we investigate the PLI for measuring the interdependency of cortical source signals (CSSs) recorded in the Electroencephalogram (EEG). To this end, we consider simple analytical models for the mapping of simulated CSSs into the EEG. For these models, the PLI is investigated analytically and through numerical simulations. An evaluation is made of the sensitivity of the PLI to the amount of crosstalk between the sources through biological tissues of the head. It is found that the PLI is a useful interdependency measure for CSSs, especially when the amount of crosstalk is small. Another common interdependency measure is the coherence. A direct comparison of both measures has not been made in the literature so far. We assess the performance of the PLI and coherence for estimation and detection purposes based on, respectively, a normalized variance and a novel statistical measure termed contrast. Based on these performance measures, it is found that the PLI is similar or better than the CM in most cases. This result is also confirmed through analysis of EEGs recorded from epileptic patients

Specificity of Transmembrane Protein Palmitoylation in Yeast

Many proteins are modified after their synthesis, by the addition of a lipid molecule to one or more cysteine residues, through a thioester bond. This modification is called S-acylation, and more commonly palmitoylation. This reaction is carried out by a family of enzymes, called palmitoyltransferases (PATs), characterized by the presence of a conserved 50- aminoacids domain called “Asp-His-His-Cys- Cysteine Rich Domain” (DHHC-CRD). There are 7 members of this family in the yeast Saccharomyces cerevisiae, and each of these proteins is thought to be responsible for the palmitoylation of a subset of substrates. Substrate specificity of PATs, however, is not yet fully understood. Several yeast PATs seem to have overlapping specificity, and it has been proposed that the machinery responsible for palmitoylating peripheral membrane proteins in mammalian cells, lacks specificity altogether

Bayesian Approach to Model CD137 Signaling in Human M.tuberculosis in vitro Responses

Abstract Immune responses are qualitatively and quantitatively influenced by a complex network of receptor-ligand interactions. Among them, the CD137:CD137L pathway is known to modulate innate and adaptive human responses against Mycobacterium tuberculosis. However, the underlying mechanisms of this regulation remain unclear. In this work, we developed a Bayesian Computational Model (BCM) of in vitro CD137 signaling, devised to fit previously gathered experimental data. The BCM is fed with the data and the prior distribution of the model parameters and it returns theirposterior distribution and the model evidence, which allows comparing alternative signaling mechanisms. The BCM uses a coupled system of non-linear differential equations to describe the dynamics of Antigen Presenting Cells, Natural Killer and T Cells together with the interpheron (IFN)-c and tumor necrosis factor (TNF)-a levels in the media culture. Fast and complete mixing of the media is assumed. The prior distribution of the parameters that describe the dynamics of the immunological response was obtained from the literature and theoretical considerations Our BCM applies successively the Levenberg-Marquardt algorithm to find the maximum a posteriori likelihood (MAP); the Metropolis Markov Chain Monte Carlo method to approximate the posterior distribution of the parameters and Thermodynamic Integration to calculate the evidence of alternative hypothesis. Bayes factors provided decisive evidence favoring direct CD137 signaling on T cells. Moreover, the posterior distribution of the parameters that describe the CD137 signaling showed that the regulation of IFNc levels is based more on T cells survival than on direct induction. Furthermore, the mechanisms that account for the effect of CD137 signaling on TNF-a production were based on a decrease of TNF-a production by APC and, perhaps, on the increase in APC apoptosis. BCM proved to be a useful tool to gain insight on the mechanisms of CD137 signaling during human response against Mycobacterium tuberculosis.Fil: Darío A Fernández Do Porto. UNIV.DE BUENOS AIRES. FAC.DE CS.EXACTAS Y NATURALES. UNIV.DE BUENOS AIRES. FAC.DE CS.EXACTAS Y NATURALES. INST QUIM FISICA D/L/MATERIALES MED AMB Y ENERG.Fil: Jerónimo Auzmendi. UNIV.DE BUENOS AIRES. FAC.DE CS.EXACTAS Y NATURALES. INST QUIM FISICA D/L/MATERIALES MED AMB Y ENERG.Fil: Delfina Peña. UNIV.DE BUENOS AIRES. FAC.DE CS.EXACTAS Y NATURALES. CONSEJO NAC.DE INVEST.CIENTIF.Y TECNICAS. OFICINA DE COORDINACION ADMINISTRATIVA CIUDAD UNIVERSITARIA. INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES. UNIV.DE BUENOS AIRES. FAC.DE CS.EXACTAS Y NATURALES. DTO.DE QUIMICA BIOLOGICA.Fil: Veronica E Garcia. CONSEJO NAC.DE INVEST.CIENTIF.Y TECNICAS. OFICINA DE COORDINACION ADMINISTRATIVA CIUDAD UNIVERSITARIA. INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES.Fil: Luciano Moffatt. UNIV.DE BUENOS AIRES. FAC.DE CS.EXACTAS Y NATURALES. INST QUIM FISICA D/L/MATERIALES MED AMB Y ENERG

PI3K Signaling in Normal B Cells and Chronic Lymphocytic Leukemia (CLL).

B cells provide immunity to extracellular pathogens by secreting a diverse repertoire of antibodies with high affinity and specificity for exposed antigens. The B cell receptor (BCR) is a transmembrane antibody, which facilitates the clonal selection of B cells producing secreted antibodies of the same specificity. The diverse antibody repertoire is generated by V(D)J recombination of heavy and light chain genes, whereas affinity maturation is mediated by activation-induced cytidine deaminase (AID)-mediated mutagenesis. These processes, which are essential for the generation of adaptive humoral immunity, also render B cells susceptible to chromosomal rearrangements and point mutations that in some cases lead to cancer. In this chapter, we will review the central role of PI3K s in mediating signals from the B cell receptor that not only facilitate the development of functional B cell repertoire, but also support the growth and survival of neoplastic B cells, focusing on chronic lymphocytic leukemia (CLL) B cells. Perhaps because of the central role played by PI3K in BCR signaling, B cell leukemia and lymphomas are the first diseases for which a PI3K inhibitor has been approved for clinical use

Synchronous chaos and broad band gamma rhythm in a minimal multi-layer model of primary visual cortex

Visually induced neuronal activity in V1 displays a marked gamma-band component which is modulated by stimulus properties. It has been argued that synchronized oscillations contribute to these gamma-band activity [... however,] even when oscillations are observed, they undergo temporal decorrelation over very few cycles. This is not easily accounted for in previous network modeling of gamma oscillations. We argue here that interactions between cortical layers can be responsible for this fast decorrelation. We study a model of a V1 hypercolumn, embedding a simplified description of the multi-layered structure of the cortex. When the stimulus contrast is low, the induced activity is only weakly synchronous and the network resonates transiently without developing collective oscillations. When the contrast is high, on the other hand, the induced activity undergoes synchronous oscillations with an irregular spatiotemporal structure expressing a synchronous chaotic state. As a consequence the population activity undergoes fast temporal decorrelation, with concomitant rapid damping of the oscillations in LFPs autocorrelograms and peak broadening in LFPs power spectra. [...] Finally, we argue that the mechanism underlying the emergence of synchronous chaos in our model is in fact very general. It stems from the fact that gamma oscillations induced by local delayed inhibition tend to develop chaos when coupled by sufficiently strong excitation.Comment: 49 pages, 11 figures, 7 table

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders