An active feedback recovery technique from disruption events induced by m=2 n=1 tearing modes in ohmically heated tokamak plasmas

We present experimental results of magnetic feedback control on the m=2, n=1 tearing mode in RFX-mod operated as a circular ohmically heated tokamak. The feedback suppression of the non-resonant m=2, n=1 Resistive Wall Mode (RWM) in q(a)<2 plasmas is a well-established result of RFX-mod. The control of the tearing counterpart, which develops in q(a)>2 equilibrium, is instead a more difficult issue. In fact, the disruption induced by a growing amplitude m=2, n=1 tearing mode can be prevented by feedback only when the resonant surface q=2 is close to the plasma edge, namely 2<q(a)<2.5, and the electron density does not exceed approximately half of the Greenwald limit. A combined technique of tearing mode and q(a) control has been therefore developed to recover the discharge from the most critical conditions: the potentially disruptive tearing mode is converted into the relatively benign RWM by suddenly decreasing q(a) below 2. The experiments demonstrate the concept with 100% of successful cases. The q(a) control has been performed through the plasma current, given the capability of the toroidal loop-voltage power supply of RFX-mod. We also propose a path for controlling q(a) by acting on the plasma shape, which could be applied to medium size elongated tokamaks

Investimento em Intangível e Criação de Valor: uma Análise das Companhias Abertas Brasileiras no Período 2000-2014

Este artigo analisa a relação entre investimentos em ativos intangíveis e criação de valor das empresas brasileiras de capital aberto no Brasil, medida pelo Q de Tobin. No artigo, aplica-se o system GMM em um painel de dados formado por 208 firmas com ações negociadas na Bolsa de Valores (B3) brasileira no período 2000-2014. Os dados são provenientes da Economática e Instituto Nacional de Propriedade Industrial (INPI). O principal resultado mostra impactos positivos do fluxo de investimento em ativos intangíveis (mas não seu acúmulo) sobre o valor das empresas

Efficient Delivery of MicroRNA and AntimiRNA Molecules Using an Argininocalix[4]arene Macrocycle

MicroRNAs (miRNAs) are short non-coding RNA molecules acting as gene regulators by repressing translation or by inducing degradation of the target RNA transcripts. Altered expression of miRNAs may be involved in the pathogenesis of many severe human diseases, opening new avenues in the field of therapeutic strategies, i.e., miRNA targeting or miRNA mimicking. In this context, the efficient and non-toxic delivery of premiRNA and antimiRNA molecules might be of great interest. The aim of the present paper is to determine whether an argininocalix[4]arene is able to efficiently deliver miRNA, premiRNA, and antimiRNA molecules to target cells, preserving their biological activity. This study points out that (1) the toxicity of argininocalix[4]arene 1 is low, and it can be proposed for long-term treatment of target cells, being that this feature is a pre-requisite for the development of therapeutic protocols; (2) the delivery of premiRNA and antimiRNA molecules is efficient, being higher when compared with reference gold standards available; and (3) the biological activity of the premiRNAs and antimiRNAs is maintained. This was demonstrated using the argininocalix[4]arene 1 in miRNA therapeutic approaches performed on three well-described experimental model systems: (1) the induction of apoptosis by antimiR-221 in glioma U251 cells; (2) the induction of apoptosis by premiR-124 in U251 cells; and (3) the inhibition of pro-inflammatory IL-8 and IL-6 genes in cystic fibrosis IB3-1 cells. Our results demonstrate that the argininocalix[4]arene 1 should be considered a very useful delivery system for efficient transfer to target cells of both premiRNA and antimiRNA molecules, preserving their biological activity

A peptide-nucleic acid targeting miR-335-5p enhances expression of cystic fibrosis transmembrane conductance regulator (CFTR) gene with the possible involvement of the CFTR scaffolding protein NHERF1

(1) Background: Up-regulation of the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) might be of great relevance for the development of therapeutic protocols for cystic fibrosis (CF). MicroRNAs are deeply involved in the regulation of CFTR and scaffolding proteins (such as NHERF1, NHERF2 and Ezrin). (2) Methods: Content of miRNAs and mRNAs was analyzed by RT-qPCR, while the CFTR and NHERF1 production was analyzed by Western blotting. (3) Results: The results here described show that the CFTR scaffolding protein NHERF1 can be upregulated in bronchial epithelial Calu-3 cells by a peptide-nucleic acid (PNA) targeting miR-335-5p, predicted to bind to the 3′-UTR sequence of the NHERF1 mRNA. Treatment of Calu-3 cells with this PNA (R8-PNA-a335) causes also up-regulation of CFTR. (4) Conclusions: We propose miR-335-5p targeting as a strategy to increase CFTR. While the efficiency of PNA-based targeting of miR-3355p should be verified as a therapeutic strategy in CF caused by stop-codon mutation of the CFTR gene, this approach might give appreciable results in CF cells carrying other mutations impairing the processing or stability of CFTR protein, supporting its application in personalized therapy for precision medicine

Inclusão x formação de professor

Uma nova perspectiva surge no sistema educacional: a inclusão, que contempla a construção de uma sociedade não excludente em que a diversidade é respeitada. Na declaração de Salamanca (1884), “inclusão e participação são essenciais à dignidade humana e ao gozo e exercício dos direitos humanos. No campo da educação, tal se reflete no desenvolvimento de estratégias que procuram proporcionar uma equalização genuína de oportunidades”. Assim sendo, é importante que haja ressignificação da formação de professores para o desenvolvimento de culturas, políticas e práticas de inclusão. O presente trabalho teve como objetivo investigar as deficiências na capacitação dos profissionais de educação com relação à orientação inclusiva para os alunos com necessidades educacionais especiais. A pesquisa evidenciou-se por meio de uma abordagem qualitativa, onde os sujeitos não são concebidos como seres passivos e sim como sujeitos históricos possuidores de constituição subjetiva construída a partir da inserção em determinado contexto social e segundo suas singularidades. Conforme Lüdke e André (1986) a “pesquisa qualitativa supõe o contato direto e prolongado do pesquisador com o ambiente e a situação que está sendo investigada, via de regra através do trabalho intensivo de campo”. A pesquisa realizou-se em uma escola pública de ensino fundamental do Distrito Federal. Essa escola é de ensino regular com turmas de inclusão. Os sujeitos da pesquisa foram: professor regente, diretor, coordenador pedagógico e aluno. Foram aplicados os seguintes instrumentos: análise documental, observação participante e entrevistas semi-estruturadas. Os resultados foram organizados em três categorias de análise: inclusão, mediação e formação de professores. Nesta escola, a inclusão não acontece, pois não há recursos físicos, administrativos e pedagógicos necessários para atender os alunos com necessidades educacionais especiais. A mediação é evidenciada, pois professores e alunos produzem conhecimento em interação, num diálogo coletivo que oportuniza uma aprendizagem significativa. A escola não se reconhece como espaço de formação para professores, as coordenações coletivas não favorecem estudos que gerem movimentos de busca e de renovação por novas teorias e novas práticas. As categorias apontam pontos positivos e negativos, sendo que na escola pesquisada, os pontos negativos sobressaem-se sobre os positivos. A análise dos resultados remete à conclusão de que há um longo caminho a ser percorrido, pois a inclusão ainda encontra-se em processo de construção e a deficiência na formação dos professores dificulta e até mesmo, inviabiliza esse processo. Entretanto a mediação se efetiva num processo dinâmico e coletivo que se dá na interação professor-aluno-meio

Complexation to cationic microspheres of double-stranded peptide nucleic acid-DNA chimeras exhibiting decoy activity

The major aim of this paper was to determine whether cationic microspheres (CM), consisting of the permeable polymer Eudragit\uc2\uae RS 100 plus the cationic surfactant dioctadecyl-dimethyl-ammonium bromide (DDAB18), could bind to double-stranded peptide nucleic acid PNA-DNA-PNA (PDP) chimeras exhibiting decoy activity against NF-\uce\ubaB transcription factors. Microspheres were produced by the 'solvent evaporation method' and centrifugation at 500, 1,000 and 3,000 rpm to obtain different-sized microparticles. Microsphere morphology, size and size distribution were determined by optical and electron microscopy observations. In order to determine their binding activity, double-stranded DNA-based and PDP-based decoy molecules were incubated with different amounts of microparticles in the presence of 100 ng of either32P-labeled DNA-DNA or DNA-PDP hybrid molecules or cold PDP-PDP hybrids. The complexes were analyzed by agarose gel electrophoresis. The resistance of32P-labeled DNA-DNA and DNA-PDP molecules in the presence of serum or cellular extracts was evaluated after binding to CM by gel electrophoresis analysis. DDAB18Eudragit RS 100 microspheres are able to bind to DNA-PDP and PDP-PDP hybrids, to deliver these molecules to target cells and to protect DNA-PDP molecules from enzymatic degradation in simulated biological fluids. In addition, when assayed in ex vivo conditions, DDAB18Eudragit RS 100 microspheres exhibited low toxicity. The results presented in this paper demonstrate that CM can be considered suitable formulations for pharmacogenomic therapy employing double-stranded PDP chimeras

Guaranteed optimal reachability control of reaction-diffusion equations using one-sided Lipschitz constants and model reduction

We show that, for any spatially discretized system of reaction-diffusion, the approximate solution given by the explicit Euler time-discretization scheme converges to the exact time-continuous solution, provided that diffusion coefficient be sufficiently large. By "sufficiently large", we mean that the diffusion coefficient value makes the one-sided Lipschitz constant of the reaction-diffusion system negative. We apply this result to solve a finite horizon control problem for a 1D reaction-diffusion example. We also explain how to perform model reduction in order to improve the efficiency of the method

Altered multisensory temporal integration in obesity

Eating is a multisensory behavior. The act of placing food in the mouth provides us with a variety of sensory information, including gustatory, olfactory, somatosensory, visual, and auditory. Evidence suggests altered eating behavior in obesity. Nonetheless, multisensory integration in obesity has been scantily investigated so far. Starting from this gap in the literature, we seek to provide the first comprehensive investigation of multisensory integration in obesity. Twenty male obese participants and twenty male healthy-weight participants took part in the study aimed at describing the multisensory temporal binding window (TBW). The TBW is defined as the range of stimulus onset asynchrony in which multiple sensory inputs have a high probability of being integrated. To investigate possible multisensory temporal processing deficits in obesity, we investigated performance in two multisensory audiovisual temporal tasks, namely simultaneity judgment and temporal order judgment. Results showed a wider TBW in obese participants as compared to healthy-weight controls. This holds true for both the simultaneity judgment and the temporal order judgment tasks. An explanatory hypothesis would regard the effect of metabolic alterations and low-grade inflammatory state, clinically observed in obesity, on the temporal organization of brain ongoing activity, which one of the neural mechanisms enabling multisensory integration