Towards compact laser-driven accelerators: exploring the potential of advanced double-layer targets.

The interest in compact, cost-effective, and versatile accelerators is increasing for many applications of great societal relevance, ranging from nuclear medicine to agriculture, pollution control, and cultural heritage conservation. For instance, Particle Induced X-ray Emission (PIXE) is a non-destructive material characterization technique applied to environmental analysis that requires MeV-energy ions. In this context, superintense laser-driven ion sources represent a promising alternative to conventional accelerators. In particular, the optimization of the laser-target coupling by acting on target properties results in an enhancement of ion current and energy with reduced requirements on the laser system. Among the advanced target concepts that have been explored, one appealing option is given by double-layer targets (DLTs), where a very low-density layer, which acts as an enhanced laser absorber, is grown to a thin solid foil. Here we present some of the most recent results concerning the production with deposition techniques of advanced DLTs for laser-driven particle acceleration. We assess the potential of these targets for laser-driven ion acceleration with particle-in-cell simulations, as well as their application to PIXE analysis of aerosol samples with Monte Carlo simulations. Our investigation reports that MeV protons, accelerated with a ∼20 TW compact laser and optimized DLTs, can allow performing PIXE with comparable performances to conventional sources. We conclude that compact DLT-based laser-driven accelerators can be relevant for environmental monitoring.

Concordance Analysis of ALK Gene Fusion Detection Methods in Patients with Non-Small-Cell Lung Cancer from Chile, Brazil, and Peru.

About 4% to 7% of the non-small-cell lung cancer patients have anaplastic lymphoma kinase (ALK) rearrangements, and specific targeted therapies improve patients' outcomes significantly. ALK gene fusions are detected by immunohistochemistry or fluorescent in situ hybridization as gold standards in South America. Next-generation sequencing-based assays are a reliable alternative, able to perform simultaneous detection of multiple events from a single sample. We analyzed 4240 non-small-cell lung cancer samples collected in 37 hospitals from Chile, Brazil, and Peru, where ALK rearrangements were determined as part of their standard of care (SofC) using either immunohistochemistry or fluorescent in situ hybridization. A subset of 1450 samples was sequenced with the Oncomine Focus Assay (OFA), and the concordance with the SofC tests was measured. An orthogonal analysis was performed using a real-time quantitative PCR echinoderm microtubule-associated protein-like 4-ALK fusion detection kit. ALK fusion prevalence is similar for Chile (3.67%; N = 2142), Brazil (4.05%; N = 1013), and Peru (4.59%; N = 675). Although a comparison between OFA and SofC assays showed similar sensitivity, OFA had significantly higher specificity and higher positive predictive value, which opens new opportunities for a more specific determination of ALK gene rearrangements.

A comparison between SOLiD 5500XLand Ion Torrent PGM-derived miRNA expression profiles in two breast cell lines.

Next-generation sequencing (NGS) platforms allow the analysis of hundreds of millions of molecules in a single sequencing run, revolutionizing many research areas. NGS-based microRNA studies enable expression quantification in unprecedented scale without the limitations of closed-platforms. Yet, whereas a massive amount of data produced by these platforms is available, comparisons of quantification/discovery capabilities between platforms are still lacking. Here we compare two NGS-platforms: SOLiD and PGM, by evaluating their microRNA identification/quantification capabilities using two breast-derived cell-lines. A high expression correlation (R2 > 0.9) was achieved, encompassing 97% of the miRNAs, and the few discrepancies in miRNA counts were attributable to molecules that have very low expression. Quantification divergences indicative of artefactual representation were seen for 14 miRNAs (higher in SOLiD-reads) and another 10 miRNAs more abundant in PGM-data. An inspection of these revealed an increased and statistically significant count of uracyls and uracyl-stretches for PGM-enriched miRNAs, compared to SOLiD and to the miRBase. In parallel, adenines and adenine-stretches were enriched for SOLiDderived miRNA reads. We conclude that, whereas both platforms are overall consistent and can be used interchangeably for microRNA expression studies, particular sequence features appear to be indicative of specific platform bias, and their presence in microRNAs should be considered for database-analyses.

The impact of HER2 overexpression on the miRNA and circRNA transcriptomes in two breast cell lines and their vesicles.

HER2 upregulation is related with poor outcome in many tumor types. Whereas anti-HER2 treatment is the standard approach as adjuvant therapy in HER2-overexpressing breast cancer, the frequent relapses reinforce the need for alternative treatments. Here we used next-generation sequencing (NGS) to evaluate miRNAs and circRNAs in the cell-lines HB4a and C5.2, where the latter is a HER2-overexpressing clone of the former, and also from two different populations of their secreted extracellular vesicles. Whereas circRNA-levels were stable, we found at least 16 miRNAs apparently modulated by HER2-expression. The miR223-3p, miR-421 and miR-21-5p were validated in an independent cohort of 431 breast cancer patients from The Cancer Genome Atlas (TCGA). The consistent modulation of these molecules and their possible involvement in the HER2-axis makes them promising new targets to overcome HER2-activation.

Socioeducação: origem, significado e implicações para o atendimento socioeducativo / Socio-education: origin, meaning and implications for socio-educational services

The notion of socio-education emerged with the implementation of socio-educational measures set forth by the Brazilian Child and Adolescent Statute, representing an important achievement for the assistance to and work with adolescents who have committed offenses. However, despite being a breakthrough, said statute was not clear as to the conception of socio-educational support that can effectively promote the development of activities with adolescents subjected to socio-educational measures. In order to overcome the fragility and inaccuracy of what is meant by socio-education, this paper presents and discusses conceptual and theoretical elements relating to socio-education and socio-educational practices, aiming to bring greater clarity to the professional practices of those who work daily with adolescents under socio-educational measures. Socio-education is a set of programs, services and activities developed through the articulation between educational practices, social demands and human rights in order to allow for new stances among youths, without, however, breaking with ethical and social rules. This leads to the understanding that, beyond the judicial process, the socio-educational measure includes a network of actionswhich, by means of pedagogical and intentional practices, has potential to redefine trajectories marked by offenses and build up new life projects. Managers and professionals responsible for implementing socio-educational services must discuss crystallized and reductionist meanings in order to consider the perpetration of offenses as a complex and multi-determined phenomenon through which socio-educational activities of critical and emancipatory nature can cause transformative breaks

La noción de socio educación apareció en el Estatuto del Niño y del Adolescente con la aplicación de medidas socioeducativas, lo que representa un logro importante en la atención e intervención con adolescentes que han cometido delitos. A pesar de que representa un gran avance, el estatuto no aclaró sobre la concepción de socio educación que puede promover las intervenciones con los adolescentes en el cumplimiento de las medidas socioeducativas. Con el fin de superar la vaguedad de lo que se entiende por socio educación, en este estudio se presentan los elementos conceptuales y teóricos relativos al socio educación y las prácticas socioeducativas, con el objetivo de contribuir a una mejor claridad de las prácticas profesionales de los que trabajan a diario con adolescentes. Partiendo del concepto de la educación social, socio educación es un conjunto articulado de programas, servicios y actividades desarrollados a partir de la vinculación entre las prácticas educativas, las demandas sociales y los derechos humanos con el fin de movilizar a las nuevas posiciones jóvenes, pero sin romper las reglas éticas y sociales. Aparte del proceso judicial, la medida socioeducativa incluye acciones conjuntas y la creación de redes que a través de acciones educativas e intencionales posibiliten la redefinición de las trayectorias ofensivas y el desarrollo de nuevos proyectos de vida. Los gestores y los profesionales encargados de la ejecución del servicio socioeducativo deben discutir los significados acerca de los actos ilegales con el fin de considerar su complejidad, en el que las actividades socioeducativas pueden generar roturas transformadoras

Socioeducação: origem, significado e implicações para o atendimento socioeducativo / Socio-education: origin, meaning and implications for socio-educational services / Socio educación: origen, significado e implicaciones para servicios socioeducativos

A noção de socioeducação surgiu no Estatuto da Criança e do Adolescente quando da implementação das medidas socioeducativas, representando importante conquista na atenção e intervenção com adolescentes autores de atos infracionais. Contudo, apesar de representar um avanço, o estatuto pouco esclareceu sobre a concepção de socioeducação que pudesse subsidiar intervenções efetivamente promotoras do desenvolvimento dos adolescentes em cumprimento de medidas socioeducativas. Buscando superar a fragilidade e imprecisão do que se entende por socioeducação, o presente artigo apresenta e discute elementos conceituais e teóricos relativos à socioeducação e às práticas socioeducativas, almejando contribuir para conferir maior clareza e intencionalidade às práticas profissionais daqueles que trabalham diariamente com adolescentes em medida socioeducativa. Partindo da concepção de educação social, a socioeducação é um conjunto articulado de programas, serviços e ações desenvolvidos a partir da articulação entre práticas educativas, demandas sociais e direitos humanos com o objetivo de mobilizar nos jovens novos posicionamentos sem, contudo, romper com as regras éticas e sociais vigentes...

The notion of socio-education emerged with the implementation of socio-educational measures set forth by the Brazilian Child and Adolescent Statute, representing an important achievement for the assistance to and work with adolescents who have committed offenses. However, despite being a breakthrough, said statute was not clear as to the conception of socio-educational support that can effectively promote the development of activities with adolescents subjected to socio-educational measures. In order to overcome the fragility and inaccuracy of what is meant by socio-education, this paper presents and discusses conceptual and theoretical elements relating to socio-education and socio-educational practices, aiming to bring greater clarity to the professional practices of those who work daily with adolescents under socio-educational measures...

La noción de socio educación apareció en el Estatuto del Niño y del Adolescente con la aplicación de medidas socioeducativas, lo que representa un logro importante en la atención e intervención con adolescentes que han cometido delitos. A pesar de que representa un gran avance, el estatuto no aclaró sobre la concepción de socio educación que puede promover las intervenciones con los adolescentes en el cumplimiento de las medidas socioeducativas. Con el fin de superar la vaguedad de lo que se entiende por socio educación, en este estudio se presentan los elementos conceptuales y teóricos relativos al socio educación y las prácticas socioeducativas, con el objetivo de contribuir a una mejor claridad de las prácticas profesionales de los que trabajan a diario con adolescentes. Partiendo del concepto de la educación social, socio educación es un conjunto articulado de programas, servicios y actividades desarrollados a partir de la vinculación entre las prácticas educativas, las demandas sociales y los derechos humanos con el fin de movilizar a las nuevas posiciones jóvenes, pero sin romper las reglas éticas y sociales...

Estudo de vesículas extracelulares em linhagens celulares e empacientes com câncer de mama positivas para a amplificação deERBB2/HER2 / Study of extracellular vesicles in cell lines and breast cancer patients positive for ERBB2/HER2 amplification

As Vesículas Extracelulares (EVs) são organelas essenciais para processos fisiológicos e aparentemente contribuem para o desenvolvimento de diversas doenças através da transferência entre células de ácidos nucléicos e proteínas contidos em seu interior. Deste modo, EVs são promissoras como fonte de biomarcadores. Neste trabalho, avaliamos o conteúdo de EVs secretadas in vitro e in vivo, com o intuito de identificar moléculas relacionadas com a amplificação do oncogene ERBB2/HER2 e com estádios de progressão tumoral de câncer de mama HER2+. Utilizando um modelo de duas linhagens celulares - HB4a derivada de mama normal e C5.2, um clone de HB4a que superexpressa o oncogene ERBB2/HER2 - isolamos duas populações de EVs provenientes do meio de cultura celular condicionado: 20K, enriquecida para microvesículas e 100K, enriquecida para exossomos. Demonstramos que a superexpressão de um único oncogene (ERBB2/HER2) altera o perfil proteômico das EVs secretadas pela células C5.2. Proteínas capazes de induzir a transformação maligna foram encontradas superexpressas nas duas populações de EVs da linhagem C5.2, e interessantemente observamos uma maior expressão de HER2 nas EVs em relação a esta mesma linhagem celular. Uma análise por sequenciamento de nova geração do transcriptoma completo (RNAs pequenos e longos) das EVs e células secretoras revelou centenas de transcritos diferencialmente representados entre as duas linhagens, que podem estar direta ou indiretamente sendo afetados pela superexpressão de HER2, e possibilitou uma investigação das moléculas preferencialmente incorporadas nas EVs...

Extracellular vesicles (EVs) are essential organelles involved in physiological processes and apparently contribute to the development of several pathological conditions by the transfer between cells of nucleic acid and protein cargo. Therefore, EVs are promising sources of biomarkers. In the study presented here, we evaluated the content of EVs secreted in vitro and in vivo, aiming to identify molecules related to ERBB2/HER2 oncogene amplification and with progressing tumor stages of HER2+ breast cancer. Using a model of two cell lines – HB4a derived from normal breast and C5.2, a clone of HB4a that overexpresses ERBB2/HER2 – we isolated two populations of EVs derived from the conditioned cell culture medium: 20K, enriched for microvesicles and 100K, enriched for exosomes. We demonstrate that the overexpression of a single oncogene (ERBB2/HER2) alters the proteomic landscape of EVs secreted by C5.2 cells. Proteins capable of inducing malignant transformation were found overexpressed in both EVs populations secreted by C5.2 cells, and interestingly, we observed an increased expression of HER2 in the EVs compared to the secreting cells. Next generation sequencing analysis of the entire transcriptome (long and short RNAs) of EVs and secreting cells revealed hundreds of transcripts differentially expressed between the two cell lines, which may be directly or indirectly affected by HER2 overexpression, and enabled the investigation of molecules that are preferentially shuttled in EVs...

Comportamentos de risco na alta adolescência: um estudo de caso em proposta transdisciplinar

Este trabalho é resultante do desafio de se buscar ampliar o escopo de compreensão e análise do(s) sentido(s) da manifestação de comportamentos e práticas de risco, com ênfase no consumo de bebidas alcoólicas, no período referido como alta adolescência (a partir dos 17 anos de idade) e no contexto pós-tradicional de uma alta modernidade na qual a vida social implica numa reflexividade que se torna parte das formas de ação adotadas pelos indivíduos e grupos, de tal forma que a modernidade acaba sendo constituída por e através de conhecimento reflexivamente aplicado e socialmente refratado. Ao partir de inquietações advindas da práxis psicológica clínica, pela aplicação de um viés inicial de base comportamental, cada novo encontro clínico realizado com o paciente aqui chamado Murilo - recortado como um estudo de caso propício à discussão da temática em questão - serviu para constatar a importância de se desenvolver um olhar mais abrangente que recorresse a aportes das ciências humanas para uma relativização e expansão de noções como: comportamentos, escolhas e exposição ao 'risco', relacionadas ao indivíduo em sua interação com o mundo. Partiu-se, assim, rumo a uma proposta de investigação efetuada em dimensão transdisciplinar - mais que formulada em meras e habituais descrições e enquadramentos psicológicos comportamentais que priorizam a função e o contexto em detrimento do sentido. O paciente foi abordado na concretude de sua situação e relação existencial, na temporalidade e historicidade de seu existir e ressaltando-se a singularidade ilustrada pela proposta de compreensão do caso, como possibilidade de transcendência de conhecimentos e diagnósticos univocamente psicológicos, para além dos limites de análise das condições espaço-temporais clínicas compartilhadas em consultório. Ao conclamar uma proposta transdisciplinar ao caso e tema foram buscados contribuições e aportes, inter-relacionados em interfaces possíveis.

This work results from the challenge of trying to expand the scope of comprehension and analysis of the meaning(s) of manifestation of risk behaviors and practices, with an emphasis on the consumption of alcoholic beverages in the period referred as late adolescence (starting at 17 years of age) and in the post-traditional context of a late modernity in which social life implies in a reflexivity that becomes part of the ways of action adopted by individuals and groups, in such a way that modernity ends up being constituted by and through reflexively applied and socially refracted knowledge. Starting from inquietudes aroused from the clinical psychological praxis, through an initial behaviorist frame, each new clinical session with the patient here called Murilo – portrayed as a case study propitious to the discussion of the theme at hand – helped to evidence the importance of developing a broader glance which would call upon contributions from human sciences in order to relativize and expand notions such as: behaviors, choices and exposure to “risk”, related to the interaction of the individual with the world. The aim was to set out towards a proposal of investigation carried out in a transdiciplinary dimension – beyond the usual descriptions and psychological behavioral frames which prioritize function and context to the detriment of meaning. The patient was approached in the concreteness of his existential relation and situation, in the temporality and historicity of his existence and through the highlighting of the singularity illustrated by the case´s proposal of comprehension, as a possibility of transcendence of solely psychological diagnoses and knowledge, far beyond the limits of analysis and clinical space-time conditions shared in the psychologist’s office. In calling out for a transdisciplinary proposal to the case and theme, contributions and data were interrelated in possible interfaces to the following areas...(AU)