The mass accretion rate of galaxy clusters: a measurable quantity

We explore the possibility of measuring the mass accretion rate (MAR) of galaxy clusters from their mass profiles beyond the virial radius $R_{200}$. We derive the accretion rate from the mass of a spherical shell whose inner radius is $2R_{200}$, whose thickness changes with redshift, and whose infall velocity is assumed to be equal to the mean infall velocity of the spherical shells of dark matter halos extracted from $N$-body simulations. This approximation is rather crude in hierarchical clustering scenarios where both smooth accretion and aggregation of smaller dark matter halos contribute to the mass accretion of clusters.Nevertheless, in the redshift range $z=[0,2]$, our prescription returns an average MAR within $20-40 \%$ of the average rate derived from the merger trees of dark matter halos extracted from $N$-body simulations. The MAR of galaxy clusters has been the topic of numerous detailed numerical and theoretical investigations, but so far it has remained inaccessible to measurements in the real universe. Since the measurement of the mass profile of clusters beyond their virial radius can be performed with the caustic technique applied to dense redshift surveys of the cluster outer regions, our result suggests that measuring the mean MAR of a sample of galaxy clusters is actually feasible. We thus provide a new potential observational test of the cosmological and structure formation models.Comment: 11 pages, 7 figures, 5 tables, minor text modifications to match the published version, typos correcte

Epigenetic Analysis in Human Neurons: Considerations for Disease Modeling in PD

Parkinson’s disease (PD) is the second most common neurodegenerative disorder next to Alzheimer’s disease. Most PD cases are considered to be sporadic and despite considerable scientific effort, the underlying cause(s) still remain(s) enigmatic. In particular, it is unknown to which extent epigenetic alterations contribute to the pathophysiology of this devastating disorder. This is partly due to the fact that appropriate PD models are not yet available. Moreover, epigenetic patterns and mechanisms are species specific and murine systems reflect only a few of the idiosyncrasies of human neurons. For several years now, patient-specific stem cell-derived neural and non-neural cells have been employed to overcome this limitation allowing the analysis and establishment of humanized disease models for PD. Thus, several studies tried to dissect epigenetic alterations such as aberrant DNA methylation or microRNA patterns using lund human mesencephalic cell lines or neurons derived from (patient-specific) induced pluripotent stem cells. These studies demonstrate that human neurons have the potential to be used as model systems for the study of epigenetic modifications in PD such as characterizing epigenetic changes, correlating epigenetic changes to gene expression alterations and hopefully using these insights for the development of novel therapeutics. However, more research is required to define the epigenetic (age-associated) landscape of human in vitro neurons and compare these to native neurons before they can be established as suitable models for epigenetic studies in PD. In this review, we summarize the knowledge about epigenetic studies performed on human neuronal PD models, and we discuss advantages and current limitations of these (stem cell-derived) neuronal models for the study of epigenetic alterations in PD

SIMPLES NACIONAL: UM ESTUDO DE CASO SOBRE AS VANTAGENS E DESVANTAGENS DE UMA INDÚSTRIA DE FABRICAÇÃO DE RESERVATÓRIO E ESTRUTURAS METÁLICAS NO MUNICÍPIO DE ÁLVARES FLORENCE-SP

The Simples Nacional is a simplified tax regime, applicable to Microenterprises (ME) and Small Businesses (EPP). It was created on December 14, 2006 by the Federal Government, with the aim of reducing the bureaucratic process of companies. An important aspect of this tax regime is the unification of tax collection, in which amounts are collected through a single guide, which generates greater efficiency in companies' tax and accounting processes. The objective of this work is to demonstrate the advantages and disadvantages of the option for the Simples Nacional regime, applicable to a Microenterprise in the industry sector, compared to other tax regimes. Through the analysis of revenue, the research showed that the Simples Nacional is the tax regime with the least burden of taxes.Simples Nacional es un régimen tributario simplificado, aplicable a Microempresas (ME) y Pequeñas Empresas (EPP). Fue creado el 14 de diciembre de 2006 por el Gobierno Federal, con el objetivo de reducir el proceso burocrático de las empresas. Un aspecto importante de este sistema tributario es la unificación de la recaudación tributaria, en la cual los montos son recaudados a través de una guía única, lo que genera mayor eficiencia en los procesos tributarios y contables de las empresas. La metodología de investigación utilizada para este estudio se caracteriza por ser cualitativa con carácter descriptivo y exploratorio, realizada a través de un estudio y caso, utilizando investigación bibliográfica y análisis de datos secundarios. El objetivo de este trabajo es realizar una comparación entre los regímenes tributarios, demostrando las ventajas y desventajas de la opción Simples Nacional, aplicable a una Microempresa en la industria. Mediante el análisis de la facturación, la investigación arrojó que Simples Nacional es el régimen tributario con menor carga tributaria.O Simples Nacional é um regime tributário simplificado, aplicável às Microempresas (ME) e às Empresas de Pequeno Porte (EPP). Foi criado em 14 de dezembro de 2006 pelo Governo Federal, com o intuito de reduzir o processo burocrático das empresas. Um aspecto importante deste regime tributário é a unificação da arrecadação dos impostos, no qual os valores são recolhidos através de guia única, o que gera maior eficiência nos processos fiscais e contábeis das empresas. A metodologia de pesquisa utilizada para este estudo caracteriza-se como qualitativa de cunho descritiva e exploratória, realizada por meio de um estudo e caso, utilizando a pesquisa bibliográfica e análise de dados secundários. O objetivo deste trabalho é fazer a comparação entre os regimes tributários, demonstrando as vantagens e desvantagens da opção pelo do Simples Nacional, aplicável a uma Microempresa do ramo de indústria. Através da análise do faturamento a pesquisa evidenciou que o Simples Nacional é o regime tributário com menor oneração de tributos

SIMPLES NACIONAL: UM ESTUDO DE CASO SOBRE AS VANTAGENS E DESVANTAGENS DE UMA INDÚSTRIA DE FABRICAÇÃO DE RESERVATÓRIO E ESTRUTURAS METÁLICAS NO MUNICÍPIO DE ÁLVARES FLORENCE-SP

The Simples Nacional is a simplified tax regime, applicable to Microenterprises (ME) and Small Businesses (EPP). It was created on December 14, 2006 by the Federal Government, with the aim of reducing the bureaucratic process of companies. An important aspect of this tax regime is the unification of tax collection, in which amounts are collected through a single guide, which generates greater efficiency in companies' tax and accounting processes. The objective of this work is to demonstrate the advantages and disadvantages of the option for the Simples Nacional regime, applicable to a Microenterprise in the industry sector, compared to other tax regimes. Through the analysis of revenue, the research showed that the Simples Nacional is the tax regime with the least burden of taxes.Simples Nacional es un régimen tributario simplificado, aplicable a Microempresas (ME) y Pequeñas Empresas (EPP). Fue creado el 14 de diciembre de 2006 por el Gobierno Federal, con el objetivo de reducir el proceso burocrático de las empresas. Un aspecto importante de este sistema tributario es la unificación de la recaudación tributaria, en la cual los montos son recaudados a través de una guía única, lo que genera mayor eficiencia en los procesos tributarios y contables de las empresas. La metodología de investigación utilizada para este estudio se caracteriza por ser cualitativa con carácter descriptivo y exploratorio, realizada a través de un estudio y caso, utilizando investigación bibliográfica y análisis de datos secundarios. El objetivo de este trabajo es realizar una comparación entre los regímenes tributarios, demostrando las ventajas y desventajas de la opción Simples Nacional, aplicable a una Microempresa en la industria. Mediante el análisis de la facturación, la investigación arrojó que Simples Nacional es el régimen tributario con menor carga tributaria.O Simples Nacional é um regime tributário simplificado, aplicável às Microempresas (ME) e às Empresas de Pequeno Porte (EPP). Foi criado em 14 de dezembro de 2006 pelo Governo Federal, com o intuito de reduzir o processo burocrático das empresas. Um aspecto importante deste regime tributário é a unificação da arrecadação dos impostos, no qual os valores são recolhidos através de guia única, o que gera maior eficiência nos processos fiscais e contábeis das empresas. A metodologia de pesquisa utilizada para este estudo caracteriza-se como qualitativa de cunho descritiva e exploratória, realizada por meio de um estudo e caso, utilizando a pesquisa bibliográfica e análise de dados secundários. O objetivo deste trabalho é fazer a comparação entre os regimes tributários, demonstrando as vantagens e desvantagens da opção pelo do Simples Nacional, aplicável a uma Microempresa do ramo de indústria. Através da análise do faturamento a pesquisa evidenciou que o Simples Nacional é o regime tributário com menor oneração de tributos

Analysis of α-synuclein species enriched from cerebral cortex of humans with sporadic dementia with Lewy bodies.

Since researchers identified α-synuclein as the principal component of Lewy bodies and Lewy neurites, studies have suggested that it plays a causative role in the pathogenesis of dementia with Lewy bodies and other 'synucleinopathies'. While α-synuclein dyshomeostasis likely contributes to the neurodegeneration associated with the synucleinopathies, few direct biochemical analyses of α-synuclein from diseased human brain tissue currently exist. In this study, we analysed sequential protein extracts from a substantial number of patients with neuropathological diagnoses of dementia with Lewy bodies and corresponding controls, detecting a shift of cytosolic and membrane-bound physiological α-synuclein to highly aggregated forms. We then fractionated aqueous extracts (cytosol) from cerebral cortex using non-denaturing methods to search for soluble, disease-associated high molecular weight species potentially associated with toxicity. We applied these fractions and corresponding insoluble fractions containing Lewy-type aggregates to several reporter assays to determine their bioactivity and cytotoxicity. Ultimately, high molecular weight cytosolic fractions enhances phospholipid membrane permeability, while insoluble, Lewy-associated fractions induced morphological changes in the neurites of human stem cell-derived neurons. While the concentrations of soluble, high molecular weight α-synuclein were only slightly elevated in brains of dementia with Lewy bodies patients compared to healthy, age-matched controls, these observations suggest that a small subset of soluble α-synuclein aggregates in the brain may drive early pathogenic effects, while Lewy body-associated α-synuclein can drive neurotoxicity

Consensus classification of human prion disease histotypes allows reliable identification of molecular subtypes: an inter-rater study among surveillance centres in Europe and USA

The current classification of human sporadic prion diseases recognizes six major phenotypic subtypes with distinctive clinicopathological features, which largely correlate at the molecular level with the genotype at the polymorphic codon 129 (methionine, M, or valine, V) in the prion protein gene and with the size of the protease-resistant core of the abnormal prion protein, PrP(Sc) (i.e. type 1 migrating at 21 kDa and type 2 at 19 kDa). We previously demonstrated that PrP(Sc) typing by Western blotting is a reliable means of strain typing and disease classification. Limitations of this approach, however, particularly in the interlaboratory setting, are the association of PrP(Sc) types 1 or 2 with more than one clinicopathological phenotype, which precludes definitive case classification if not supported by further analysis, and the difficulty of fully recognizing cases with mixed phenotypic features. In this study, we tested the inter-rater reliability of disease classification based only on histopathological criteria. Slides from 21 cases covering the whole phenotypic spectrum of human sporadic prion diseases, and also including two cases of variant Creutzfeldt-Jakob disease (CJD), were distributed blindly to 13 assessors for classification according to given instructions. The results showed good-to-excellent agreement between assessors in the classification of cases. In particular, there was full agreement (100 %) for the two most common sporadic CJD subtypes and variant CJD, and very high concordance in general for all pure phenotypes and the most common subtype with mixed phenotypic features. The present data fully support the basis for the current classification of sporadic human prion diseases and indicate that, besides molecular PrP(Sc) typing, histopathological analysis permits reliable disease classification with high interlaboratory accuracy

Development and validation of a recommended checklist for assessment of surgical videos quality: the LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS) video assessment tool

Introduction There has been a constant increase in the number of published surgical videos with preference for open-access sources, but the proportion of videos undergoing peer-review prior to publication has markedly decreased, raising questions over quality of the educational content presented. The aim of this study was the development and validation of a standard framework for the appraisal of surgical videos submitted for presentation and publication, the LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS) video assessment tool. Methods An international committee identified items for inclusion in the LAP-VEGaS video assessment tool and finalised the marking score utilising Delphi methodology. The tool was finally validated by anonymous evaluation of selected videos by a group of validators not involved in the tool development. Results 9 items were included in the LAP-VEGaS video assessment tool, with every item scoring from 0 (item not presented in the video) to 2 (item extensively presented in the video), with a total marking score ranging from 0 to 18. The LAP-VEGaS video assessment tool resulted highly accurate in identifying and selecting videos for acceptance for conference presentation and publication, with high level of internal consistency and generalisability. Conclusions We propose that peer review in adherence to the LAP-VEGaS video assessment tool could enhance the overall quality of published video outputs.[GRAPHICS]