Size limiting in Tsallis statistics

Power law scaling is observed in many physical, biological and socio-economical complex systems and is now considered as an important property of these systems. In general, power law exists in the central part of the distribution. It has deviations from power law for very small and very large step sizes. Tsallis, through non-extensive thermodynamics, explained power law distribution in many cases including deviation from the power law, both for small and very large steps. In case of very large steps, they used heuristic crossover approach. In real systems, the size is limited and thus, the size limiting factor is important. In the present work, we present an alternative model in which we consider that the entropy factor q decreases with step size due to the softening of long range interactions or memory. This explains the deviation of power law for very large step sizes. Finally, we apply this model for distribution of citation index of scientists and examination scores and are able to explain the entire distribution including deviations from power law.Comment: 22 pages, 8 figure

N-benzylpiperidine derivatives as α7 nicotinic receptor antagonists

This document is the accepted manuscript version of a Published Work that appeared in final form in ACS Chemical Neuroscience 7.8, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see DOI: 10.1021/acschemneuro.6b00122.A series of multitarget directed propargylamines, as well as other differently susbstituted piperidines have been screened as potential modulators of neuronal nicotinic acetylcholine receptors (nAChRs). Most of them showed antagonist actions on α7 nAChRs. Especially, compounds 13, 26, and 38 displayed submicromolar IC50 values on homomeric α7 nAChRs, whereas they were less effective on heteromeric α3β4 and α4β2 nAChRs (up to 20-fold higher IC50 values in the case of 13). Antagonism was concentration dependent and noncompetitive, suggesting that these compounds behave as negative allosteric modulators of nAChRs. Upon the study of a series of less complex derivatives, the N-benzylpiperidine motif, common to these compounds, was found to be the main pharmacophoric group. Thus, 2-(1-benzylpiperidin-4-yl)-ethylamine (48) showed an inhibitory potency comparable to the one of the previous compounds and also a clear preference for α7 nAChRs. In a neuroblastoma cell line, representative compounds 13 and 48 also inhibited, in a concentration-dependent manner, cytosolic Ca2+ signals mediated by nAChRs. Finally, compounds 38 and 13 inhibited 5-HT3A serotonin receptors whereas they had no effect on α1 glycine receptors. Given the multifactorial nature of many pathologies in which nAChRs are involved, these piperidine antagonists could have a therapeutic potential in cases where cholinergic activity has to be negatively modulated.This work was supported by grants SAF2011-22802 to S.S., SAF2012-33304 to J.M.-C., CSD2008-00005 (the Spanish Ion Channel Initiative-CONSOLIDER INGENIO 2010) to M.C. from the Spanish Ministry of Science and Innovation (Ministerio de Economía y Competitividad)

Seasonal and interannual fluctuation of the microbial soil community in a maize field under long-term conservation agriculture management

Soil’s microbiological settlement in a Zea mays parcel under long-term agricultural practices aiming to minimize the disruption of the soil’s structure, composition and natural biodiversity was analyzed by culture-dependent and culture-independent processes. Of the different processes, morphological-type differentiation of cultured microflora produced the best results and, while Polymerase Chain Reaction (PCR)-agarose electrophoresis has also provided us with reliable ones, soil PCR-DGGE (Denaturing Gradient Gel Electrophoresis) did not, which may occur because of the dependence of the method on the practice. Over a three-year period, this soil seemed very stable as its C/N ratio remained roughly constant and available for microbial growth. Because no soil overturning occurred, we were able to maintain most of the cultured microbial population whose fluctuations depended only on edaphoclimatic conditions. The number of cultured bacteria, molds, total microorganisms, and the biodiversity indices were usually lower in the driest season (fall) than in the rest of the year, except for Acinetobacter and Stenotrophomonas, which showed the opposite behavior. Coincident with the rise in temperature during the summer, the relative abundance of Gram+ bacteria increased, mostly reflecting an increase in the spore-forming bacteria Streptomyces and Bacillus. Despite these variations, the evenness index and the quantity of distinct microbiological life remained practically unaltered, recovering their maximum levels when the proper edaphoclimatic conditions were present, which indicates the long-term stability of the microbial community in this soil. The performed study put forward important insights for assessing the sustainability of maize production under long-term conservation agriculture management systems, highlighting that adequate management might prevent the degradation of soil quality, thus contributing to promote sustainable agricultureinfo:eu-repo/semantics/publishedVersio

The effect of mPEGA/EHA ratio and copolymer composition on the solution behavior of amphiphilic, comb‐shape copolymers synthesized via Cu(0)‐mediated SET‐LRP for potential drug delivery applications

Comb-shape, block copolymers from hydrophilic poly(ethylenglycol) monomethyl ether acrylate (mPEGA, A) and hydrophobic 2-ethylhexyl acrylate (EHA, B) are synthesized by copper(0)-mediated single-electron transfer living radical polymerization (SET-LRP) via sequential addition of the two monomers, resulting in different compositions (AB, ABA, BAB, BA), molar masses, and mPEGA/EHA ratios. All polymers show narrow molar mass distributions and molecular weights of 7.7-25.50 kg mol-1, demonstrating precise control over the polymerization and molecular weights through the utilization of SET-LRP. Kinetic experiments are conducted to investigate the polymerization behavior of mPEGA and EHA in N,N-dimethylformamide as a rather uncommon solvent for SET-LRP further underlining a living-type polymerization. Amphiphilic properties are investigated by critical micelle concentration (CMC) measurements and formation of micelles in water. A reverse relation between mPEGA/EHA ratio and CMC values reveals that an increased hydrophobicity leads to decreased CMC values. The self-assembly behavior of polymers in water confirms the formation of uniform and stable micelles in water with a size between 12 and 184 nm depending on the composition of the polymers. With increased hydrophilicity, micelle sizes increase as well. In vitro tests of the obtained polymers show excellent biocompatibility even at high concentrations further affirming their suitability for drug delivery applications.Federal Ministry of Education and ResearchBaden‐Württemberg Ministry of ScienceGerman Federal and State Government

Pesquisa em enfermagem psiquiátrica: concepções e expectativas de enfermeiros que atuam em instituições psiquiátricas

This research has as objects of study the conceptions and expectations of the clinical nurses in psychiatric institutions about the research developed in this area. It has the purpose to identify conceptions and expectations, enabling the identification of the process of dissemination and utilization of the research in the attention and administration of psychiatric nursing care. It was developed with nurses that work in psychiatric instituitions at Salvador, in March, 1997. 25 nurses who worked in the period were interviewed expressing their opinions concerning the theme in study, through semi-structured interview. Results were quantitatively analised, based on the theoretical-methodological design of the Social Representations. It was possible to conclude that the great part of the nurses interviewed mentioned that they did not have acess to research in this area, as well as demonstrated difficulty to find the relations and influence of these research in their service, however they admit its importance to personal and professional development, that certainly, reflects on nursing care.Esta investigación tiene como objeto de estudio las concepciones y expectativas de los enfermeros actuantes en instituiciones psiquiátricas sobre las investigaciones desarolladas en esta area. Tiene como objetivo, identificar esas concepciones y expectativas, permitindo esbozar el proceso de divulgación y utilización de esas investigaciones en la atención y administración de la assistencia de enfermería psiquiátrica. Fue desarrollada con enfermeros que trabajam en instituciones psiquiátricas de la ciudad de Salvador, durante el mes de marzo de 1997. Fueron entrtevistados 25 enfermeros que se encontraban en servicio en el periodo previsto para la realización de la colecta de datos, quienes emitieron sus opiniones a través de guía de entrevista semi-estructurada. Los resultados fueron cualitativamente analizados y se apoyaron en los principios teórico-metodológicos de las Representaciones Sociales, permitindo concluir que la mayoría de los enfermeros entrevistados refirió no tener acceso a las investigaciones específicas del área, y demostró dificultad en establecer relación e influencia desas investigaciones en sus servicios aunque admitieron su importancia en le desarrollo personal y profesional, lo que repercutiría sobremanera en la asistencia prestada por los enfermeros.Esta investigação tem como objeto de estudo as concepções e expectativas de enfermeiros que atuam em instituições psiquiátricas, em relação às pesquisas desenvolvidas nessa área. Tem como objetivo, identificar essas concepções e expectativas, possibilitando traçar um perfil sobre o processo de divulgação e utilização dessas pesquisas na atenção e administração da assistência de Enfermagem Psiquiátrica. Foi desenvolvida junto a enfermeiros que trabalham em instituições psiquiátricas da cidade de Salvador, durante o mês de março do corrente ano. Foram entrevistados 25 enfermeiros que se encontravam em serviço no período previsto para a realização da coleta de dados, os quais emitiram suas opiniões concernentes ao tema em apreço, através de um roteiro de entrevista semi-estruturada. Os resultados, qualitativamente analisados, apoiaram-se nos pressupostos teórico-metodológicos das Representações Sociais, permitindo concluir-se que a maioria dos enfermeiros entrevistados referiu não ter acesso às pesquisas específicas da área, bem como demonstrou dificuldade em estabelecer relação e influência dessas pesquisas nos seus serviços, muito embora admitissem sua importância para o desenvolvimento pessoal e profissional, o que, por certo repercutiria, sobremaneira, na assistência prestada pelo enfermeiro

Structured Observations Reveal Slow HIV-1 CTL Escape

The existence of viral variants that escape from the selection pressures imposed by cytotox- ic T-lymphocytes (CTLs) in HIV-1 infection is well documented, but it is unclear when they arise, with reported measures of the time to escape in individuals ranging from days to years. A study of participants enrolled in the SPARTAC (Short Pulse Anti-Retroviral Thera- py at HIV Seroconversion) clinical trial allowed direct observation of the evolution of CTL es- cape variants in 125 adults with primary HIV-1 infection observed for up to three years. Patient HLA-type, longitudinal CD8+ T-cell responses measured by IFN- γ ELISpot and lon- gitudinal HIV-1 gag , pol , and nef sequence data were used to study the timing and preva- lence of CTL escape in the participants whilst untreated. Results showed that sequence variation within CTL epitopes at the first time point (within six months of the estimated date of seroconversion) was consistent with most mutations being transmitted in the infecting viral strain rather than with escape arising within the first few weeks of infection. Escape arose throughout the first three years of infection, but slowly and steadily. Approximately one third of patients did not drive any new escape in an HLA-restricted epitope in just under two years. Patients driving several escape mutations during these two years were rare and the median and modal numbers of new escape events in each patient were one and zero re- spectively. Survival analysis of time to escape found that possession of a protective HLA type significantly reduced time to first escape in a patient (p = 0.01), and epitopes escaped faster in the face of a measurable CD8+ ELISpot response (p = 0.001). However, even in an HLA matched host who mounted a measurable, specific, CD8+ response the average time before the targeted epitope evolved an escape mutation was longer than two year

HIV-1 DNA predicts disease progression and post-treatment virological control

In HIV-1 infection, a population of latently infected cells facilitates viral persistence despite antiretroviral therapy (ART). With the aim of identifying individuals in whom ART might induce a period of viraemic control on stopping therapy, we hypothesised that quantification of the pool of latently infected cells in primary HIV-1 infection (PHI) would predict clinical progression and viral replication following ART. We measured HIV-1 DNA in a highly characterised randomised population of individuals with PHI. We explored associations between HIV-1 DNA and immunological and virological markers of clinical progression, including viral rebound in those interrupting therapy. In multivariable analyses, HIV-1 DNA was more predictive of disease progression than plasma viral load and, at treatment interruption, predicted time to plasma virus rebound. HIV-1 DNA may help identify individuals who could safely interrupt ART in future HIV-1 eradication trials

A framework for variable content document generation with multiple actors

“NOTICE: this is the author’s version of a work that was accepted for publication in Information and Software Technology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Information and Software Technology, Volume 56, Issue 9, September 2014, Pages 1101–1121 DOI10.1016/j.infsof.2013.12.006Context - Advances in customization have highlighted the need for tools supporting variable content document management and generation in many domains. Current tools allow the generation of highly customized documents that are variable in both content and layout. However, most frameworks are technology-oriented, and their use requires advanced skills in implementation-related tools, which means their use by end users (i.e. document designers) is severely limited. Objective - Starting from past and current trends for customized document authoring, our goal is to provide a document generation alternative in which variants are specified at a high level of abstraction and content reuse can be maximized in high variability scenarios. Method Based on our experience in Document Engineering, we identified areas in the variable content document management and generation field open to further improvement. We first classified the primary sources of variability in document composition processes and then developed a methodology, which we called DPL based on Software Product Lines principles to support document generation in high variability scenarios. Results - In order to validate the applicability of our methodology we implemented a tool DPLfw to carry out DPL processes. After using this in different scenarios, we compared our proposal with other state-of-the-art tools for variable content document management and generation. Conclusion - The DPLfw showed a good capacity for the automatic generation of variable content documents equal to or in some cases surpassing other currently available approaches. To the best of our knowledge, DPLfw is the only framework that combines variable content and document workflow facilities, easing the generation of variable content documents in which multiple actors play different roles.This work has been partially funded by the Spanish Ministerio de Economia y Competitividad under Grant TIPEx (TIN2010-19859-C03-03).Gómez Llana, A.; Penadés Gramage, MC.; Canos Cerda, JH.; Borges, MR.; Llavador Campos, M. (2014). A framework for variable content document generation with multiple actors. Information and Software Technology. 56(9):1101-1121. https://doi.org/10.1016/j.infsof.2013.12.006S1101112156

Effects of highly active antiretroviral therapy with nelfinavir in vertically HIV-1 infected children: 3 years of follow-up. Long-term response to nelfinavir in children

BACKGROUND: Antiretroviral treatment (ART) in children has special features and consequently, results obtained from clinical trials with antiretroviral drugs in adults may not be representative of children. Nelfinavir (NFV) is an HIV-1 Protease Inhibitor (PI) which has become as one of the first choices of PI for ART in children. We studied during a 3-year follow-up period the effects of highly active antiretroviral therapy with nelfinavir in vertically HIV-1 infected children. METHODS: Forty-two vertically HIV-infected children on HAART with NFV were involved in a multicentre prospective study. The children were monitored at least every 3 months with physical examinations, and blood sample collection to measure viral load (VL) and CD4+ cell count. We performed a logistic regression analysis to determinate the odds ratio of baseline characteristics on therapeutic failure. RESULTS: Very important increase in CD4+ was observed and VL decreased quickly and it remained low during the follow-up study. Children with CD4+ <25% at baseline achieved CD4+ >25% at 9 months of follow-up. HIV-infected children who achieved undetectable viral load (uVL) were less than 40% in each visit during follow-up. Nevertheless, HIV-infected children with VL >5000 copies/ml were less than 50% during the follow-up study. Only baseline VL was an important factor to predict VL control during follow-up. Virological failure at defined end-point was confirmed in 30/42 patients. Along the whole of follow-up, 16/42 children stopped HAART with NFV. Baseline characteristics were not associated with therapeutic change. CONCLUSION: NFV is a safe drug with a good profile and able to achieve an adequate response in children

Identification of Essential Sequences for Cellular Localization in BRMS1 Metastasis Suppressor

10 páginas, 5 figuras. PMID: 19649328 [PubMed] PMCID: PMC2713406BACKGROUND: Breast cancer metastasis suppressor 1 (BRMS1) reduces the number and the size of secondary tumours in a mouse model without affecting the growth of the primary foci upon its re-expression. Knockdown of BRMS1 expression associates with metastasis. The molecular details on BRMS1 mechanism of action include its ability to function as a transcriptional co-repressor and consistently BRMS1 has been described as a predominantly nuclear protein. Since cellular distribution could represent a potential mechanism of regulation, we wanted to characterize BRMS1 sequence motifs that might regulate its cellular distribution. According to its amino acids sequence, BRMS1 contain two putative nuclear localization signals, however none of them has been proved to work so far. METHODOLOGY/PRINCIPAL FINDINGS: By using well known in vivo assays to detect both nuclear import and export signal, we have characterized, in the present study, one functional nuclear localisation signal as necessary and sufficient to promote nuclear transport. Additionally, the outcome of a directed yeast two-hybrid assay identify importin alpha6 as a specific partner of BRMS1 thus speculating that BRMS1 nuclear import could be specifically mediated by the reported nuclear transporter. Besides, the combination of a computational searching approach along the utilization of a nuclear export assay, identified a functional motif within the BRMS1 sequence responsible for its nuclear export, that resulted not affected by the highly specific CRM1 inhibitor Leptomycin-B. Interspecies heterokaryon assay demonstrate the capability of BRMS1 to shuttle between the nuclear and cytosolic compartments CONCLUSIONS/SIGNIFICANCE: Our results show for the first time that BRMS1 contains both nuclear import and export signals enabling its nucleo-cytoplasmic shuttling. These findings contributes new data for the understanding of the BRMS1 functions and allow us to speculate that this phenomenon could represent a novel mechanism for regulating the activity of BRMS1 or its associated cytosolic partnersThis work was supported by Spanish Ministerio de Ciencia y Tecnología (Grant SAF2006-10269), Ministerio de Ciencia e Innovación (Grant SAF2008-04048-E) and by a grant from Fundación Mutua Madrileña.Peer reviewe