Regulação do comportamento alimentar e novos alvos terapêuticos

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Veículos e vetores em terapia génica

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

AS PRÁTICAS DE TREINAMENTO COMO MECANISMOS DISCIPLINARES E DE REGULAÇÃO EM ORGANIZAÇÃO DE DESENVOLVIMENTO E COMÉRCIO DE SOFTWARE DE RECURSOS HUMANOS

Este trabalho tem como objetivo investigar na prática organizacional as articulações e desarticulações entre as práticas de treinamento, vistas como mecanismo que disciplina o indivíduo (normas e padronização de procedimentos de trabalho), e as diretrizes de práticas de treinamento, vistas como mecanismo de regulação (normas, padrões de conduta), das relações entre a organização e os funcionários. A pesquisa permite trazer para o ambiente acadêmico científico um aprofundamento quanto aos mecanismos de poder disciplinar exercidos pela organização estudada sobre os funcionários e os mecanismos de regulação sobre o mesmo fenômeno práticas de treinamento , além de explorar a questão da distinção e complementaridade entre ambos. Foi utilizada pesquisa qualitativa e uma proposta teóricometodológica de análise de conteúdo e análise de discurso, a partir de uma amostra indicativa e intencional, sendo a empresa do ramo de desenvolvimento e comércio de software de recursos humanos. Utilizou-se de três instrumentos para a coleta de dados: a entrevista em profundidade, observações do pesquisador e pesquisa documental. As análises feitas entre a teoria e os dados empíricos comprovaram a existência de articulações e desarticulações entre os mecanismos, além de outros achados, confirmados através da norma de treinamento e dos depoimentos dos entrevistados.

Branqueamento de Capitais e Bitcoin: A Regulação e o Fenómeno da Inovação

O branqueamento de capitais surge em meados dos anos 30, tendo como base as operações realizadas com fundos provenientes de atividades ilícitas, que eram ―lavados‖ e reintegrados no sistema financeiro. Perceber-se-á que, desde essa altura, as práticas utilizadas no branqueamento de capitais têm sofrido várias alterações, tendo evoluído no que à complexidade de operações diz respeito, o que será compreensível se forem analisadas as alterações a que o sistema financeiro tem sido exposto. Muitas vezes, a regulação e o quadro legal não acompanham a evolução de instrumentos dos mercados financeiros, dando oportunidade para o aproveitamento dessas lacunas em atividades menos lícitas. O ponto de partida para este trabalho foi o de perceber como é que o fenómeno do branqueamento de capitais se comporta quando confrontado com a inovação das moedas virtuais e em especial, da bitcoin, a moeda virtual com maior sucesso atualmente. A dimensão que a moeda bitcoin assumiu no mercado levou a que um cada vez maior número de investigadores se debruçasse sobre esta moeda procurando entender a sua génese e funcionamento, bem como, perceber quais seriam os seus pontos favoráveis ou desfavoráveis. A bitcoin apresenta-se no mercado como uma moeda virtual de simples utilização, que pode ser transacionada em qualquer parte do mundo. A moeda cresceu, quer em valor e quer em volume de transações, de forma significativa, nos últimos anos. No presente estudo, são abordados ambos os temas com o intuito de ser analisada a possibilidade de existir uma relação entre o branqueamento de capitais e as transações realizadas em bitcoins. Após uma revisão bibliográfica sobre ambos os temas, bem como, da análise de um conjunto de notícias recolhidas, conclui-se a existência de uma ténue linha que divide esta moeda da prática de branquear capitais e que a associação de ambas é reconhecida por várias entidades reguladoras

O princípio da eficiência administrativa na regulação da prestação do serviço de voz sobre internet - VoIP

The present work aims to demonstrate the link of the principle of efficiency - as expressed in the Constitution of 1988, by Constitutional Amendment No. 19 - with regulatory agencies, more specifically the ANATEL (National Telecommunications Agency). It also includes this principle’s importance to regulation - to monitor and manage public services - as well as when an activity will be considered efficient, keeping in mind that agencies are subjected to other principles of public administration. The increasing use of telephony has enabled further development of technologies that provide improvements in the provision of this service. The VoIP (Voice over IP), is nothing more than a technological breakthrough that directly targets the providers of conventional telephone service, both by modifying the business working for a long time with the same technology as the amount of new competitors’ dispute on market share. It also analyses the difficulty of understanding and definition of what is VoIP telephony, its growth and the threats that the traditional and mostly which is ANATEL’s role concerning this telephony technology. As regulator of the telecommunications service, ANATEL not yet regulated the voice telephony service using the IP protocol. What looks over the years is that ANATEL exercise its regulatory function to provide better conditions for competition among providers of VoIP and traditional telephone companies, obviously some difficulties are expected, given that VoIP is a technology that provides two services, through conventional telephony and using the internet.

Universalização do acesso à saúde e regulação dos planos privados de assistência à saúde: a atuação regulatória da ANS como instrumento de harmonia contratual e viabilização do papel suplementar da iniciativa privada na efetivação do direito social à saúde

While essential to human nature, health and life have been protected since ancient times by various areas of knowledge, particularly by the Law, given its dynamics within the regulation of social interactions. In Brazil, health has been granted major importance by the Federal Constitution of 1988, which, disrupting the dictatorial authoritarianism, inaugurating a Social State and focusing on the values of freedom and human dignity, raises health to the condition of a social right, marked predominantly by an obligational bias directed, primarily, to the State, through the enforcement of public policies. Although, given the limitation of the State action to the reserve for contingencies, it turns clear that an universalizing access to public health is impossible, seen that the high cost of medical provisions hinders the State to meet all the health needs of the rightholders. As a result of the inefficiency of the State, the effort of the Constituent Assembly of 1988 in creating a hybrid health system becomes nuclear, which, marked by the possibility of exploration of healthcare by the private initiative, assigns to the private enterprise a key role in supplementing the public health system, especially through the offer of health insurance plans. At this point, however, it becomes clear that health provisions rendered by the private agents are not unlimited, which involves discussions about services and procedures that should be excluded from the contractual coverage, for purposes of sectoral balance, situation which draws the indispensability of deliberations between Fundamental Rights on one hand, related to the protection of health and life, and contractual principles on the other hand, connected to the primacy of private autonomy. At this point, the importance of the regulation undertaken by the ANS, Brazilian National Health Agency, appears primordial, which, by means of its seized broad functions, considerable autonomy and technical discretion, has conditions to implement an effective control towards the harmonization of the regulatory triangle, the stability and development of the supplementary health system and, consequently, towards the universalization of the right to health, within constitutional contours. According to this, the present essay, resorting to a broad legislative, doctrinal and jurisprudential study, concludes that economic regulation over the private healthcare sector, when legitimately undertaken, provides progress and stability to the intervening segment and, besides, turns healthcare universalization feasible, in a way that it can not be replaced efficiently by any other State function.

Caracterização de um homólogo de HINT1 em cana-de-açúcar encontrado em bibliotecas subtrativas de CDNA para floração

The sugarcane is a monocot plant grown in tropical and subtropical regions, with Brazil being the largest producer. Despite its economic importance, little is known about the molecular flowering process in sugarcane. This physiological process can promote a loss up to 60% in sugar or bioethanol. Thus, this work had as objective characterize a HINT1 homologous gene previously identified in subtractive libraries of flowering. Genomic analysis of gene and promoter region structure allowed the observation that there are at least two distinct genes homologous to HINT on sugarcane. Bioinformatics analyses showed the conservation of the characteristic protein domain of HIT superfamily and indicate a phylogenetic relationship associated to cell location. Moreover, a possible relation with the SBTILISIN-like protein family through the information available in interatomas was observed. This suggests that the HINT gene of sugarcane can be related to plant development, there are several possibilities of interactions in the regulation of floral induction process, because the sequences present in regulatory regions indicate that differential expression of HINT was related to with climatic factors in the Northeast region of Brazil as well as to biotic stress and phytohormones. Furthermore, the sugarcane phenotypes indicate that the influence of HINT may happen due to product accumulation of its enzymatic activity. For these characteristics this gene can be used as a marker in the selection of new varieties.

Benchmarking e regulação do setor de distribuição de energia elétrica nacional: proposta para avaliação dos custos operacionais eficientes

In Brazil, the National Agency of Electric Energy (ANEEL) represents the energy regulator. The rates review have been one of its main tasks, which establish a pricing practice at a level to cover the efficient operating costs and also the appropriate return of the distributors investments. The changes in the procedures to redefine the efficient costs and the several studies on the methodologies employed to regulate this segment denote the challenge faced by regulators about the best methodological strategy to be employed. In this context, this research aims to propose a benchmarking evaluation applied to the national regulation system in the establishment of efficient operating costs of electricity distribution utilities. The model is formulated to promote the electricity market development, partnering with government policies ant to society benefit. To conduct this research, an integration of Data Envelopment Analysis (DEA) with the Stochastic Frontier Analysis (SFA) is adopted in a three stages procedure to correct the efficiency in terms of environmental effects: (i) evaluation by means of DEA to measure operating costs slacks of the utilities, in which environmental variables are omitted; (ii) The slacks calculated in the first stage are regressed on a set of environmental variables by means of SFA and operating costs are adjusted to account the environmental impact and statistical noise effects; and, (iii) reassess the performance of the electric power distribution utilities by means of DEA. Based on this methodology it is possible to obtain a performance evaluation exclusively expressed in terms of management efficiency, in which the operating environment and statistical noise effects are controlled.

Construção de bibliotecas de cDNAs subtraídos a partir das sementes de Mamona submetidas à estresse hídrico e análise in silico de transcritos potencialmente expressos sob condições de estresse: Metalotioneina, proteína reprimida por auxina de 12.5 kDa e Glutelina tipo-A3

Estresses ambientais abióticos são fatores que causam respostas ao nível molecular, fisiológico e morfológico em plantas, dependendo também de sua intensidade e duração. É visto que algumas espécies apresentam tolerância a condições estressantes e ao mesmo tempo são fontes naturais de matéria prima para indústria. Nesse contexto encontra-se a mamona (Ricinus comunnis L.), principal fonte de óleo de rícino valorizado por suas aplicações farmacêuticas e principalmente industriais, vem sendo usada como cultura em regiões onde a disponibilidade de água é reduzida, usada como fonte de renda para agricultura da região nordeste brasileira. Visto que pouco se sabe sobre as respostas moleculares que levam essa planta a tolerar regiões secas e como as sementes, principais foco de interesse, respondem a essa escassez, nesse trabalho foram construídas duas bibliotecas de cDNAs, onde a partir de uma abordagem subtrativa, continham RNAs diferencialmente expressos em sementes de plantas mamona submetidas ao estresse hídrico durante 5 dias (biblioteca L7), e a outra RNAs diferencialmente expressos em sementes controle (biblioteca L5). A biblioteca L7 apresentou a maior variedade de transcritos com um total de 182. A maior parte das funções estabelecidas pelo sistema Gene Ontology - GO, foram direcionadas aos “Processos Metabólicos” (526), em segundo “Respostas a estímulos” (57), o terceiro termo mais abundante foram referentes a “Desenvolvimento”(26). Já na biblioteca L5, foram encontrados 91 transcritos, com maior parte de suas funções referentes a “Processos Metabólicos”(413), em segundo “Respostas a estímulos” (8) e em terceiro Regulação (6). Alguns dos transcritos da biblioteca L7 foram escolhidos para análise por repetirem-se mais de 3x e não aparecerem na biblioteca L5, o que indica uma possível regulação positiva sobre estresse. As análises sobre Metalotioneína (4x), mostraram que a sequência de proteica apresentava os domínios conservados que a caracterizava como tipo II, onde são encontrados dois domínios funcionais ricos em cisteína com posições altamente conservadas, desempenhando a função de ligar-se a metais pesados, correlacionadas assim como a atividade de eliminação EROs e defesa contra o estresse oxidativo, além de apresentar homologia com a sequência de Bruguiera gymnorhiza, uma planta de mangue adaptada a ambientes salinos. Analisamos também os transcritos da referente a proteína AUXIN-REPRESSED 12.5 KDA (3x), apontada como sendo reprimida pelo hormônio auxina e associada ao processo de dormência da semente, é descrito em uma família gênica onde vários membros pertencem as vias de resposta ao estresse. Por último, analisamos a proteína GLUTELIN TYPE-A 3 (5x), uma importante proteína de armazenamento com caráter hidrofílico, possivelmente direcionada para o vacúolo. Em nosso trabalho foi possível observar um aumento de transcritos em relação a subtração controle, possivelmente reflexo do aumento do metabolismo da semente, tanto para resposta defensiva ao estresse hídrico quanto para o amadurecimento rápido da semente onde foram observados transcritos referentes a resposta oxidativa, controle hormonal, proteínas de reserva e produção de óleo.

Alterações hepáticas na expressão gênica e atividade da catalase e superóxido dimutase em ratos diabéticos induzidos por estreptozootocina

The correlation between the type 1 diabetes mellitus and oxidative stress have been described in several studies, however its underlying mechanisms are not fully elucidated. The present work aimed to evaluate the effects of four weeks of streptozootocin-induced (STZ) diabetes in the redox homeostasis of rat hepatocytes. Thus, the liver of male Wistar rats from control and diabetic groups were collected and the activity and expression of antioxidant enzymes, as well the main markers of oxidative stress and content of H2O2 in these tissues were measured. The diabetes induced the activity of superoxide dismutase (SOD) and the gene expression of its mitochondrial isoform, SOD2. However, the expression of SOD1, the cytoplasmic isoform, was reduced by this disease. The activity and expression of catalase (CAT), as well the expression of glutathione peroxidase 1 (GPX1) and peroxiredoxin 4 (PRX4) were drastically reduced in the hepatocytes of diabetics rats. Even with this debility in the peroxidases mRNA expression, the content of H2O2 was reduced in the liver of diabetics rats when compared to the control group. The diabetes caused an increase of lipid peroxidation and a decrease of protein thiol content, showing that this disease causes distinct oxidative effects in different cell biomolecules. Our results indicate that four week of diabetes induced by STZ is already enough to compromise the enzymatic antioxidant systems of the hepatocytes.

Referência e contra referência em saúde bucal: regulação do acesso aos centros de especialidades odontológicas

Objective Based on the system of reference and counter-reference and comprehensiveness in oral health care, we aimed to examine ways of refering users to Specialized Dental Care Centers (SDCC) and the interface between them and Primary Care. Methods This is a cross-sectional study carried out with users and dentists of SDCC in a metropolitan region of Northeast of Brazil. Analyses were descriptive, and the association test was done with chi-square. Results Six forms of entry to specialized service were identified: free demand (13.8 %) and reference by the Primary Care dentist (63.2 %) were most frequent. Users referred by the basic health unit dentist had more interest in making a counter-reference than the others (p<0.001, PR=4.65, 95 % CI: 2.74 to 7.91), while individuals without this referral had 1.49 times more difficulty obtaining care (95 % CI: 1.02 to 2.17). Referral procedures are a decisive factor for counter-references. However, the high demand for primary care services and the short supply these services can offer in the face of needs make SDCC performance difficult. Conclusion The analysis of oral health practices from the perspective of network modeling points to the service's need to establish protocols for regulation in a bid to improve access to and the quality of care provided.

Referência e contra referência em saúde bucal: regulação do acesso aos centros de especialidades odontológicas

Objective Based on the system of reference and counter-reference and comprehensiveness in oral health care, we aimed to examine ways of refering users to Specialized Dental Care Centers (SDCC) and the interface between them and Primary Care. Methods This is a cross-sectional study carried out with users and dentists of SDCC in a metropolitan region of Northeast of Brazil. Analyses were descriptive, and the association test was done with chi-square. Results Six forms of entry to specialized service were identified: free demand (13.8 %) and reference by the Primary Care dentist (63.2 %) were most frequent. Users referred by the basic health unit dentist had more interest in making a counter-reference than the others (p<0.001, PR=4.65, 95 % CI: 2.74 to 7.91), while individuals without this referral had 1.49 times more difficulty obtaining care (95 % CI: 1.02 to 2.17). Referral procedures are a decisive factor for counter-references. However, the high demand for primary care services and the short supply these services can offer in the face of needs make SDCC performance difficult. Conclusion The analysis of oral health practices from the perspective of network modeling points to the service's need to establish protocols for regulation in a bid to improve access to and the quality of care provided.

A regulação da exploração e produção de hidrocarbonetos não convencionais no Brasil

The global energy crisis triggered the possibility of unconventional hydrocarbons exploration and production, culminating in the US energy revolution as well as making other countries interested in the development of these natural resources. The justification for this research comes from Brazil's interest in the use of hydraulic fracturing techniques in unconventional resources since the Brazilian National Agency of Petroleum, Natural Gas and Biofuels (ANP) organized the 12th acquisition process and published the Resolution no. 21 of April 10, 2014. The conflict between economic viability and the social and environmental damage from exploration and production of unconventional hydrocarbons in Brazil resulted in the search for a legal solution that would consider the economic, social and environmental interests. The main purpose here is to analyze the regulation of unconventional oil exploration and production in Brazil in order to show lack of regulatory instruments so far. The specific objectives are to investigate how the lack of effective regulation may ultimately prevent the development itself, analyze the importance of systematization of a new regulatory tool for ensuring legal security and energy, identify the key negative environmental and social impacts, and suggest possibilities approaches within the new regulatory framework. The research methodology stands out the hypothetico-deductive model as approach, and the comparative model as procedural method. Moreover, the research techniques used here are performance of a theoretical and descriptive questioning over literature search, analysis of Brazilian standardization and case laws, and a brief comparative study, in order to provide suggested approaches for a new regulatory framework.

A regulação da exploração e produção de hidrocarbonetos não convencionais no Brasil

The global energy crisis triggered the possibility of unconventional hydrocarbons exploration and production, culminating in the US energy revolution as well as making other countries interested in the development of these natural resources. The justification for this research comes from Brazil's interest in the use of hydraulic fracturing techniques in unconventional resources since the Brazilian National Agency of Petroleum, Natural Gas and Biofuels (ANP) organized the 12th acquisition process and published the Resolution no. 21 of April 10, 2014. The conflict between economic viability and the social and environmental damage from exploration and production of unconventional hydrocarbons in Brazil resulted in the search for a legal solution that would consider the economic, social and environmental interests. The main purpose here is to analyze the regulation of unconventional oil exploration and production in Brazil in order to show lack of regulatory instruments so far. The specific objectives are to investigate how the lack of effective regulation may ultimately prevent the development itself, analyze the importance of systematization of a new regulatory tool for ensuring legal security and energy, identify the key negative environmental and social impacts, and suggest possibilities approaches within the new regulatory framework. The research methodology stands out the hypothetico-deductive model as approach, and the comparative model as procedural method. Moreover, the research techniques used here are performance of a theoretical and descriptive questioning over literature search, analysis of Brazilian standardization and case laws, and a brief comparative study, in order to provide suggested approaches for a new regulatory framework.

Aplicación del sistema de recombinación específica de secuencia β-six al estudio de la regulación de la expresión génica en células eucariotas y modelos animales

Las recombinasas específicas de secuencia son herramientas muy valiosas en la generación de modificaciones génicas condicionales. Estos sistemas permiten controlar la recombinación de forma específica de tejido, temporalmente, o ambas, y sortean diversas limitaciones de los sistemas de knockout (KO) convencionales, como la letalidad embrionaria o la generación de mecanismos compensatorios. Actualmente los sistemas Cre/loxP y Flp/FRT son los más empleados tanto en modelos animales como vegetales. La necesidad de realizar modificaciones más complejas en un mismo organismo hace que sea primordial caracterizar otras recombinasas que complementen a las existentes. La b recombinasa (b-rec) es originaria del plásmido pSM19035 de Streptococcus pyogenes. A diferencia de Cre y Flp, que en ausencia de factores adicionales catalizan la integración en un nuevo sustrato, la b-rec necesita un sustrato superenrollado y un cofactor de la reacción, una proteína asociada a la cromatina (como la procariota Hbsu o la eucariota HMG1). Se ha demostrado que la b-rec cataliza de forma específicamente intramolecular (resolución o inversión) la recombinación en células eucariotas, tanto de sustratos episomales como integrados en la cromatina, lo que indica que el entorno eucariota es capaz de proveer del cofactor y del superenrollamiento necesarios para que la b-rec realice su función. En este trabajo hemos determinado que la tasa de recombinación mediada por la b-rec no se ve afectada en absoluto por la deficiencia en el cofactor HMG1, alcanzando el mismo valor de recombinación en MEF KO en HMG1 que en wt. Este y otros datos confirman que en el entorno eucariota hay otras proteínas accesorias que pueden actuar de cofactores y sugiere que estas reacciones pueden ocurrir en la mayor parte de tejidos y tipos celulares. Para estudiar detalladamente el potencial de la b-rec en eucariotas desarrollamos un sistema de RAGE (activación génica mediada por recombinación) dependiente de la actividad b-rec; este sistema ha resultado funcional tanto en sustratos episomales como en sustratos integrados en la cromatina. También hemos generado un vector retroviral que porta la proteína de fusión b-Egfp, permitiendo de forma rápida y eficiente la integración y expresión funcional de nuestra proteína...