Muito se têm noticiado sobre as possibilidades de expansão do uso do gás combustível como energético no âmbito comercial e residencial, porém entende-se que tal promessa deveria ser precedida de uma vasta e ampla discussão estratégica sobre os mecanismos necessários a serem desenvolvidos pelos agentes da sociedade para que tal expansão possa se concretizar. Dentro desse enfoque, entende-se como preocupante o desconhecimento a respeito das características de produtos e serviços utilizados, bem como o baixo grau de capacitação da indústria de prestação de serviços de instalações, andando de mãos dadas com a própria indústria da construção civil. Sem produtos ou serviços adequados é difícil prever a possibilidade concreta da expansão do gás no segmento residencial. Obviamente existem as abordagens sobre mudanças culturais a respeito da utilização do gás como energético, disponibilidade de aparelhos adequados para sua utilização, fatores econômicos envolvendo o preço do gás e uma centena de outros temas complementares. Todos esses tópicos podem ser considerados estratégicos. A dissertação pretende focar o problema da conformidade e da conseqüente disponibilização de produtos e serviços ao mercado. O trabalho explora as estratégias utilizadas para provocar melhoria e capacitação de segmentos de mercado, atrelando-os à resultados de competência e competitividade, através de monitoramento da sua conformidade com requisitos de produtos e serviços previamente estabelecidos. Discorre-se sobre as estratégias passíveis de serem utilizadas para fomento do desenvolvimento deste segmento de mercado e aborda-se os modelos válidos de avaliação de conformidade existentes atualmente no Brasil, discutindo propostas para o caso específico do monitoramento da infra-estrutura de distribuição de gás combustível no país. Utilizando-se, então, de um arcabouço de estruturas teóricas, apresenta-se um caso real do ponto de vista do mercado consumidor, particularizando a atuação da Comgás no Estado de São Paulo, discorrendo sobre as preocupações da empresa com relação à conformidade no mercado e estabelecendo paralelos entre tais iniciativas, as premissas teóricas e lacunas existentes no processo. O trabalho levanta o histórico técnico sobre modelos de avaliação de conformidade, apresentando um exercício de reflexão a respeito de propostas a serem potencialmente adotadas pelo segmento de mercado no caso de construção da infra-estrutura para condução e distribuição de gás combustível aos consumidores finais. / It has been noticed about the possibilities of gas uses expansion in commercial and residential scope, however it understands that such promise would have to be preceded of a great strategic discussion concerning the necessary ways to be developed for the society agents so that such expansion can be materialize. Looking for this approach, its worry about the unfamiliarity regarding the products and services characteristics, as well as the low degree of services installations industry qualification, walking together with the building construction industry. Without adequate products or services it is difficult to foresee the concrete possibility of the gas expansion in the residential segment. Obviously its necessary to consider the aspects on cultural changes regarding the gas uses, availability of gas appliances, economic factors involving the gas price and a hundred of other complementary subjects. All these topics can be considered like strategic. The paper intends to focus the problem of the conformity and the consequent availability of products and service to the market. The work explores the strategies used to improve qualification of market segments, connecting them with the results of ability and competitiveness, through inspection of its conformity with requirements of products and services previously established. It is discoursed on the strategies to be used for promotion this market segment development and currently approaches the valid conformity evaluation models existing of conformity in Brazil, arguing proposals for the specific case of the combustible gas distribution infrastructure inspection in the country. Using the theoretical structures, it presents a real case of the consuming market point of view, distinguishing the performance of the Comgás in the São Paulo State, discoursing on the concerns of the company with regard to conformity in the market and establishing parallel between such initiatives, the theoretical premises and existing gaps in the process. The paper raises the description technician on conformity models evaluation, presenting an exercise of reflection regarding proposals to be potentially adopted for the market segment in case of infrastructure construction for gas conduction and distribution to the end consumers.

Muito se têm noticiado sobre as possibilidades de expansão do uso do gás combustível como energético no âmbito comercial e residencial, porém entende-se que tal promessa deveria ser precedida de uma vasta e ampla discussão estratégica sobre os mecanismos necessários a serem desenvolvidos pelos agentes da sociedade para que tal expansão possa se concretizar. Dentro desse enfoque, entende-se como preocupante o desconhecimento a respeito das características de produtos e serviços utilizados, bem como o baixo grau de capacitação da indústria de prestação de serviços de instalações, andando de mãos dadas com a própria indústria da construção civil. Sem produtos ou serviços adequados é difícil prever a possibilidade concreta da expansão do gás no segmento residencial. Obviamente existem as abordagens sobre mudanças culturais a respeito da utilização do gás como energético, disponibilidade de aparelhos adequados para sua utilização, fatores econômicos envolvendo o preço do gás e uma centena de outros temas complementares. Todos esses tópicos podem ser considerados estratégicos. A dissertação pretende focar o problema da conformidade e da conseqüente disponibilização de produtos e serviços ao mercado. O trabalho explora as estratégias utilizadas para provocar melhoria e capacitação de segmentos de mercado, atrelando-os à resultados de competência e competitividade, através de monitoramento da sua conformidade com requisitos de produtos e serviços previamente estabelecidos. Discorre-se sobre as estratégias passíveis de serem utilizadas para fomento do desenvolvimento deste segmento de mercado e aborda-se os modelos válidos de avaliação de conformidade existentes atualmente no Brasil, discutindo propostas para o caso específico do monitoramento da infra-estrutura de distribuição de gás combustível no país. Utilizando-se, então, de um arcabouço de estruturas teóricas, apresenta-se um caso real do ponto de vista do mercado consumidor, particularizando a atuação da Comgás no Estado de São Paulo, discorrendo sobre as preocupações da empresa com relação à conformidade no mercado e estabelecendo paralelos entre tais iniciativas, as premissas teóricas e lacunas existentes no processo. O trabalho levanta o histórico técnico sobre modelos de avaliação de conformidade, apresentando um exercício de reflexão a respeito de propostas a serem potencialmente adotadas pelo segmento de mercado no caso de construção da infra-estrutura para condução e distribuição de gás combustível aos consumidores finais. / It has been noticed about the possibilities of gas uses expansion in commercial and residential scope, however it understands that such promise would have to be preceded of a great strategic discussion concerning the necessary ways to be developed for the society agents so that such expansion can be materialize. Looking for this approach, its worry about the unfamiliarity regarding the products and services characteristics, as well as the low degree of services installations industry qualification, walking together with the building construction industry. Without adequate products or services it is difficult to foresee the concrete possibility of the gas expansion in the residential segment. Obviously its necessary to consider the aspects on cultural changes regarding the gas uses, availability of gas appliances, economic factors involving the gas price and a hundred of other complementary subjects. All these topics can be considered like strategic. The paper intends to focus the problem of the conformity and the consequent availability of products and service to the market. The work explores the strategies used to improve qualification of market segments, connecting them with the results of ability and competitiveness, through inspection of its conformity with requirements of products and services previously established. It is discoursed on the strategies to be used for promotion this market segment development and currently approaches the valid conformity evaluation models existing of conformity in Brazil, arguing proposals for the specific case of the combustible gas distribution infrastructure inspection in the country. Using the theoretical structures, it presents a real case of the consuming market point of view, distinguishing the performance of the Comgás in the São Paulo State, discoursing on the concerns of the company with regard to conformity in the market and establishing parallel between such initiatives, the theoretical premises and existing gaps in the process. The paper raises the description technician on conformity models evaluation, presenting an exercise of reflection regarding proposals to be potentially adopted for the market segment in case of infrastructure construction for gas conduction and distribution to the end consumers.

Glucagon-like peptide-1 (GLP-1) is an anti-diabetic intestinal L cell hormone. The monounsaturated fatty acid, oleic acid (OA), is an effective GLP-1 secretagogue that crosses the cell membrane by an unknown mechanism. Immunoblotting demonstrated the presence of fatty acid transport proteins (CD36 and FATP1, 3 and 4) in the murine GLUTag L cell model. The cells demonstrated specific 3H-OA uptake, which was dose-dependently inhibited by unlabeled-OA. Phloretin and SSO, inhibitors of carrier-mediated transport and CD36, respectively, also significantly decreased 3H-OA uptake, as did knocking down FATP4 by transfection of siRNA. OA dose-dependently increased GLP-1 secretion in GLUTag cells, while phloretin and FATP4 knockdown, but not SSO, decreased this response. OA injected directly into the ileum of wild-type mice increased plasma GLP-1 levels; in contrast, preliminary findings suggest decreased GLP-1 levels in FATP4 null mice at 60 min. Collectively, these findings indicate a role for FATP4 in OA-induced GLP-1 secretion.

Glucagon-like peptide-1 (GLP-1) is an anti-diabetic intestinal L cell hormone. The monounsaturated fatty acid, oleic acid (OA), is an effective GLP-1 secretagogue that crosses the cell membrane by an unknown mechanism. Immunoblotting demonstrated the presence of fatty acid transport proteins (CD36 and FATP1, 3 and 4) in the murine GLUTag L cell model. The cells demonstrated specific 3H-OA uptake, which was dose-dependently inhibited by unlabeled-OA. Phloretin and SSO, inhibitors of carrier-mediated transport and CD36, respectively, also significantly decreased 3H-OA uptake, as did knocking down FATP4 by transfection of siRNA. OA dose-dependently increased GLP-1 secretion in GLUTag cells, while phloretin and FATP4 knockdown, but not SSO, decreased this response. OA injected directly into the ileum of wild-type mice increased plasma GLP-1 levels; in contrast, preliminary findings suggest decreased GLP-1 levels in FATP4 null mice at 60 min. Collectively, these findings indicate a role for FATP4 in OA-induced GLP-1 secretion.

Introduction: Stroke is caused from the occlusion of any cerebral artery leading to cerebral ischemia, brain damage and consequent neurological impairments and disability. The primary causes of mortality in western populations is stroke. Diabetes type 2 is a high risk factor for stroke. Stroke leads to an observable increase of neural stem cell proliferation in the subventricular zone and enhances neurogenesis in the adult rodent and human brain which suggest a mechanism contributing to stroke recovery. Neurogenesis in type 2 diabetes patients is impaired. However, whether stroke-induced neurogenesis is impaired in diabetes has not been studied. Exendin-4 is a drug for clinical treatment of type 2 diabetes which has been shown to have neuroprotective properties in animal studies. However whether Exendine-4 leads to increased neurogenesis after  stroke in the diabetic brain has not been previously studied.  Aims: The specific aims of this project were to determine whether stroke-induced stem cell proliferation is impacted by diabetes in the mouse, and if Exendine-4 regulates stroke-induced stem cell proliferation in normal and diabetic mice. Material and Methods: Aged obese/type 2 diabetic mice were subjected to stroke. The Exendin-4 treatment was started 1.5 hours thereafter. Treatment was continued for one week before animals were sacrificed. Brains were isolated and the neurons were immunostained using the specific proliferation marker Ki67. Neural stem cell proliferation was quantified by counting Ki67+ cells in the ipsilateral (subventricular zone in stroke hemisphere).The estimation was assessed by stereological counts of proliferating stem cell in the subventricular zone.  Results: The number of proliferating stem cell after stroke was statistically significantly higher in the normal mice versus diabetic mice. The effect was present in both sides (control and stroke) of the subventricular zone. Exendine-4 treatment induced statistically significant increased of  stem cell proliferation in normal mice but not in diabetic mice.   Conclusions: The result of this study shows that type 2 diabetes decreased the proliferation of neural stem cell in the subventricular zone and that Exendin-4 enhanced the subventricular proliferation in a preclinical model of clinical relevance. The data suggest that the Exendin-4 treatment could be administered to normal patients suffering from stroke in the ambulance or in the emergency room although more studies are needed.

A scourge of Type I and Type II diabetes impacts the health of hundreds of millions worldwide. The number and prevalence of diabetics are expected to rise dramatically in the next two decades. Diabetes is defined by chronic hyperglycemia which can result in a number of detrimental and costly metabolic, renal, cardiovascular and neurological disorders. Identification of at risk individuals and effective blood glucose management are critical to improving diabetic outcomes and preventing hyperglycemic complications. Diabetes prevention and treatment is limited by the understanding of islet function and mass in the diabetogenic and diabetic state. The islets of Langerhans are dispersed throughout the pancreas and comprise <2% of the pancreatic mass. The reclusive nature of islet cells presents unique challenges understanding disease development. No agent capable of exclusively targeting pancreatic β-cells within the islet has been discovered and the lack of targeting agent specificity impedes efforts to: quantify β-cell mass and develop novel therapeutics. We propose β-cell targeting can be improved by targeting unique combinations of receptors simultaneously with multivalent ligands. A synthetic multivalent agent composed of two β-cell specific diabetic therapeutics, glucagon-like peptide-1 (GLP-1) and glibenclamide (Glb), targeted against the GLP-1R and the sulfonylurea-1 receptor (SUR1) is a lead compound for the development of specific bi-functional islet cell targeting agents for use in the in vivo detection and treatment of β -cells. Herein, we describe the synthesis and initial characterization of a heterobivalent ligand composed of GLP-1 coupled to Glb. The heterobivalent ligand binds to an unaltered β-cell line with increased specificity relative to a human pancreatic exocrine cell line. Additionally, receptor cross-linking modifies β-cell signaling. Exposure of β-cells to the heterobivalent ligand results in antagonism of SUR1-Ca²⁺ signaling and equipotent agonism of GLP-1R-cAMP signaling, in comparison to the cognate monomeric ligands (Glb and GLP-1). Perturbations in intracellular signaling modifies β-cell insulin secretion resulting in decreased basal insulin secretion and with maintained yet reduced ability to potentiate β-cell glucose stimulated insulin secretion. GLP-1/Glb β-cell specificity and functional modulation suggests combinatorial receptor targeting is an effective strategy for the development of bi-functional cell-specific targeting agents, warranting further investigation and optimization.

Objective: Glucagon-like peptide-1 receptor (GLP-1R) agonists have been shown to reduce atherosclerosis in non-diabetic mice. We hypothesized that treatment with GLP-1R agonists would reduce the development of atherosclerosis in diabetic Apoe-/- mice. Results: Exendin-4 treatment (10 nmol/kg/day) of high-fat diet-induced glucose-intolerant mice for 22 weeks did not significantly reduce oral glucose tolerance (P=0.62) or HbA1c (P=0.85), and did not reduce plaque size at the aortic sinus (P = 0.35). Taspoglutide treatment for 12 weeks (0.4-mg tablet/month) of diabetic mice reduced body weight (P<0.05), food intake (P<0.05), oral glucose tolerance (P<0.05), intrahepatic triglycerides (P<0.05) and cholesterol (P<0.001), and plasma IL-6 levels (P<0.01); increased insulin:glucose (P<0.05); and unaltered oral lipid tolerance (P=0.21), plasma triglycerides (P=0.45) or cholesterol (P=0.92). Nonetheless, taspoglutide unaltered aortic atherosclerosis (P=0.18, sinus; P=0.19, descending aorta) or macrophage infiltration (P=0.45, sinus; P=0.26, arch). Conclusions: GLP-1R activation in either glucose-intolerant or diabetic mice does not significantly modify the development of atherosclerosis.

Objective: Glucagon-like peptide-1 receptor (GLP-1R) agonists have been shown to reduce atherosclerosis in non-diabetic mice. We hypothesized that treatment with GLP-1R agonists would reduce the development of atherosclerosis in diabetic Apoe-/- mice. Results: Exendin-4 treatment (10 nmol/kg/day) of high-fat diet-induced glucose-intolerant mice for 22 weeks did not significantly reduce oral glucose tolerance (P=0.62) or HbA1c (P=0.85), and did not reduce plaque size at the aortic sinus (P = 0.35). Taspoglutide treatment for 12 weeks (0.4-mg tablet/month) of diabetic mice reduced body weight (P<0.05), food intake (P<0.05), oral glucose tolerance (P<0.05), intrahepatic triglycerides (P<0.05) and cholesterol (P<0.001), and plasma IL-6 levels (P<0.01); increased insulin:glucose (P<0.05); and unaltered oral lipid tolerance (P=0.21), plasma triglycerides (P=0.45) or cholesterol (P=0.92). Nonetheless, taspoglutide unaltered aortic atherosclerosis (P=0.18, sinus; P=0.19, descending aorta) or macrophage infiltration (P=0.45, sinus; P=0.26, arch). Conclusions: GLP-1R activation in either glucose-intolerant or diabetic mice does not significantly modify the development of atherosclerosis.

The syndrome known as Gastric Dilation Air Sacculitis (GDAS) has recently been described by Lumsden et al. (2002) for Chinook salmon (Oncorhynchus tshawytscha, Walbaum), in seawater (SW) culture in New Zealand. The syndrome is characterised by distended abdomens, gastric dilation and air sacculitis, increased feed conversion ratios (FCR) and mortality. Consequently, financial returns on affected stocks are greatly reduced. A study into the epidemiology and physiology of the syndrome was initiated, working with the major aquaculture company, The New Zealand King Salmon Company (NZKS). The study revealed causative factors of GDAS. GDAS was experimentally induced only in saltwater by feeding a commercially manufactured low-cohesion pelleted diet. Control groups were fed a different diet with high physical cohesion. Low-cohesion pellets have previously been associated with a high incidence of GDAS in commercial sea cages. These data implicated osmoregulatory stress and physical properties of the feed in GDAS development. In addition, gastrointestinal (GI) physiology in GDAS -affected and -control fish was characterised. The process of GDAS development in O. tshawytscha is characterised by a loss of smooth muscle tone of the stomach as it distends. Laplace's law (P= 2T/r, where P is the distending pressure, T is the tension in the wall and r is the radius of the cylinder) predicts that unless muscle mass increases, the ability of the stomach wall to contract will be lost and consequently a loss of GI motor function will result. Therefore, GI circular smooth muscle integrity in terms of (1) stimulated and maximal contractility, (2) osmoregulatory ability of the intestine and the (3) control of the GI system was studied in pathologically affected (+ve) and unaffected (-ve) smolt. Affected fish showed changes in GI circular smooth muscle function and osmoregulatory dysfunction. Feeding different diets induced distinct gastric evacuation patterns. The intestinal brake hypothesis is presented and argued to be the probable mechanism for GDAS development. GDAS (+ve) serum showed the presence of factors capable of contracting gut smooth muscle. In addition, potential humoral mediators of the intestinal brake in fish were investigated.

Submitted by Automação e Estatística (sst@bczm.ufrn.br) on 2018-07-03T14:17:15Z No. of bitstreams: 1 JeanMarioMoreiraDeLima_DISSERT.pdf: 2889834 bytes, checksum: f4a43ed1a203489a4ac1293aa8e04bf0 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2018-07-11T11:19:44Z (GMT) No. of bitstreams: 1 JeanMarioMoreiraDeLima_DISSERT.pdf: 2889834 bytes, checksum: f4a43ed1a203489a4ac1293aa8e04bf0 (MD5) / Made available in DSpace on 2018-07-11T11:19:44Z (GMT). No. of bitstreams: 1 JeanMarioMoreiraDeLima_DISSERT.pdf: 2889834 bytes, checksum: f4a43ed1a203489a4ac1293aa8e04bf0 (MD5) Previous issue date: 2018-05-28 / Atualmente, diante de um mercado cada vez mais competitivo, produzir de forma eficiente é essencial para se obter um balanço econômico positivo. Reduzir custos, realizar processos otimizados e ofertar produtos cada vez melhores são fatores que influenciam diretamente na economia de qualquer indústria. Diante disso, técnicas que podem melhorar e/ou otimizar processos, como o monitoramento da qualidade de produto ou controle avançado tornam-se fundamentais para a indústria como um todo. No caso de Unidades de Processamento de Gás Natural (UPGNs), o monitoramento da qualidade do produto produzido é intrínseco a uma produção satisfatória, e esse controle da qualidade faz-se, como na maioria dos processos químicos, através da composição química dos produtos. Entretanto, mesmo quando cromatógrafos a gás são utilizados para análise química dos componentes, tem-se lentidão no processo analítico e longos intervalos de medição são observados. Isso impede que técnicas de monitoramento em tempo real, ou de controle, sejam estabelecidas para obtenção de melhor rendimento do processo. Dentre esses produtos, em termos econômicos, o principal é o GLP (Gás Liquefeito de Petróleo), composto por propano, butano e contaminantes como etano e pentano. Neste trabalho é proposto um sistema chamado de soft sensor que faça a inferência, baseada em redes neurais, da composição do GLP, isto é, dos seus principais componentes. Dessa forma, o monitoramento, em tempo real, da qualidade do GLP produzido torna-se possível, uma vez que a medição de sua composição não será feita através do lento processo analítico. Assim, melhora-se a qualidade do processo, do produto e, consequentemente, a lucratividade. Para o desenvolvimento deste trabalho, utilizou-se uma UPGN simulada no software HYSYS, formada por uma coluna deetanizadora em série com uma coluna debutanizadora. Na instrumentação da planta, têm-se alguns controladores PIDs. O sensor virtual tem como entradas algumas das variáveis de processo desses controladores. Neste tabalho, é proposto também um sistema de correção do erro, em tempo real, do soft sensor, tendo com base a leitura da composição do GLP feita por cromatógrafos presentes no processo. Os resultados se mostraram promissores, atestando o funcionamento adequado do soft sensor. / In face of an increasingly competitive market, producing efficiently and effectively is essential for a positive economic balance. Reducing costs, optimizing processes and offering even better products are factors that directly influence the economy of any industry. In this view, techniques that can improve and / or guarantee optimization of processes, such as the monitoring of product quality or advanced and intelligent control become fundamental for the industry as a whole. In case of Natural Gas Processing Units (NGPUs), monitoring the quality of the product is intrinsic to a satisfactory production, and quality control has been done such as in most chemical processes, through the chemical composition of the products. However, even when chromatographs are used for chemical analysis of the components, the analytical process is slow and long measurement intervals are observed. This hampers real-time product monitoring or control techniques from being established to obtain better process performance.Among these products, the most important, economically speaking, is LPG (Liquefied Petroleum Gas) composed of propane, butane and contaminats such as ethane and pentane. In this work, a system called soft sensor that makes the inference of the main components of GLP based on artificial neural network is proposed. Then, the real-time monitoring of the quality of the produced LPG becomes possible, since the measurement of the composition of the LPG will not be obtained through the slow analytical process. Thus, the quality of the process, the LPG itself, consequently, its profitability are improved.In the development of this work, a simulated GNPU has been used in HYSYS, consisting of a deethanizing column in series with a debutanizer column. In the instrumentation of the plant, there are some PID controllers. The virtual sensor is based on process variables of these controllers. In this work, a real-time error correction module of the softsensor is also proposed, based on the measuruments of the LPG composition made by the chromatographs present in the process. The results are promising, attesting the adequate behavior of the soft sensor.