An introduction to the fractional continuous- time linear systems: the 21st century systems

IEEE CIRCUITS AND SYSTEMS MAGAZINE, Third Quarter

Maritime Security in the Gulf of Guinea: Issues and Solutions for the 21st Century

A producer of 5.4 M bbl/d, totalling almost half of the consumption of the entire European Union, the Gulf of Guinea is a fundamental lifeline and maritime link between Europe, the Americas and Africa. Geographically positioned as a staging post for transit originating in Latin America and coupled with its relatively porous borders, the region is also the perfect stepping stone for contraband heading to European shores. While blessed with an enviable wealth of marine and mineral resources, the region is also plagued by an ever-increasing spectre of maritime piracy; accounting for around 30% of incidents in African waters from 2003 to 2011. It is for these reasons that this research centres around the issues of maritime security in the Gulf of Guinea, with a particular focus on the first two decades of the 21st century. This research looks to examine the overall picture of the present state of play in the area, before going on to provide an analysis of potential regional developments in maritime security. This research begins with the analysis of concepts/phenomena that have played a notable role in the shaping of the field of maritime security, namely Globalisation and security issues in the post-Cold War era. The ensuing chapter then focuses in on the Gulf of Guinea and the issues dominating the field of maritime security in the region. The penultimate chapter presents a SWOT analysis, undertaken as part of this research with the aim of correlating opinions from a variety of sectors/professions regarding maritime security in the Gulf of Guinea. The final chapter builds upon the results obtained from the abovementioned SWOT analysis, presenting a series of potential proposals/strategies that can contribute to the field of maritime security in the region over the coming years. This research draws to a close with the presentation of conclusions taken from this particular investigation, as well as a final overview of the earlier presented proposals applicable to the field of maritime security during the second decade of the 21st century.

Portuguese business groups at the beginning of the 21st century: Trends, characteristics and configurations

This study considers the literature on the persistence of business groups in developed economies and analyzes the Portuguese case. The reconstruction of the largest business groups assembles information relevant to define characteristics that enable them to thrive. Increasing internationalization, more specialization in core activities and family control define these types of big businesses. New sectors also emerge as a characteristic of these business groups when compared to the ones existing 40 years ago.

The perfect paint in modern art conservation: a comparative study of 21st century vinyl emulsions

Contemporary painting places, and will continue to place, several questions about its meaning, its chemical nature, its durability and the best way to preserve it. This research aims at putting together comprehensive data on vinyl based paints, including their components, their properties, their aging behavior and their response to selected cleaning products. In this project degradation mechanisms of vinyl binders and formulations used in the 20th and 21st century were studied. Stability over time of selected vinyl polymers was assessed through natural indoor and artificially aging. The objective was to enhance knowledge and understanding of vinyl emulsion formulations and their performance over time. Overall conservation state of pictorial layers namely, adhesion, cohesion and discoloration of selected case studies from the Portuguese artist Julião Sarmento (b.1948) was correlated with the observed molecular level changes studied in laboratory experiments. Sarmento’s paintings were chosen due to conservation concerns (discoloration) on some of his works from the 90’s. Besides, research was carried out to start increasing the knowledge of what can be expected of PVAc based paints in terms of response to conservation treatments namely, surface cleaning. Artificial aging showed that the most recent formulations which are based on a poly(vinyl acetate), poly(vinyl chloride) and polyethylene terpolymer are less stable when compared to some homopolymer formulations. From the four pigments studied, titanium dioxide rutile and a carbon based black proved to be stabilizers for both types of polymer. The mixture lithopone plus calcium carbonate has showed to have a photocatalytic effect on the binders. The studied paintings showed to be in an overall good state of conservation except for the paintings created in the 90’s with white glue and a mixture of white lithoponeand calcium carbonate. Discoloration of this white paint seems to be irreversible and ongoing and is still a major concern. The disapearance of the plasticizer was the only change detected. The current works created by Sarmento are expected to be more stable as they were painted using the rutile titanium dioxide. Immersion/cleaning tests showed that vinyl based paints can be susceptible to water and organic solvents like ethanol as some evidences point to the removal/diffusion of additives from the paint. The observations made point to the need to further proceed in this research field.

The Gap Between Knowledge and Action: Obstacles, Restraints and Deficits During the Execution of Refurbishments

This article outlines the initial draft of a PhD project which investigates refurbishment or rehabilitation projects in two German cities. The study focuses on obstacles, restraints and deficits as well as factors of success, which can be identified during the execution of the refurbishments. Moreover the study examines the process of the refurbishment itself, the general conditions under which the refurbishments are being executed as well as the implementation of sustainability criteria. First the article gives a short summary of the theoretical considerations of the study. In this respect it shortly outlines the global conditions of urban development and conducting challenges for cities in the 21st century, guiding principles of a sustainable urban development as well as goals of sustainable refurbishments. Finally the article shortly describes the case studies and presents the initial results of the empirical work.

Cities and emerging networks of learning communities

In the 21st century the majority of people live in urban settings and studies show a trend to the increase of this phenomenon. Globalisation and the concentration of multinational and clusters of firms in certain places are attracting people who seek employment and a better living. Many of those agglomerations are situated in developing countries, representing serious challenges both for public and private sectors. Programmes and initiatives in different countries are taking place and best practices are being exchanged globally. The objective is to transform these urban places into sustainable learning cities/regions where citizens can live with quality. The complexity of urban places, sometimes megacities, opened a new field of research. This paper argues that in order to understand the dynamics of such a complex phenomenon, a multidisciplinary, systemic approach is needed and the creation of learning cities and regions calls for the contribution of a multitude of fields of knowledge, ranging from economy to urbanism, educational science, sociology, environmental psychology and others.

Crystallographic studies on two hyperthermophilic enzymes

Dissertation presented to obtain the Ph.D degree in Biochemistry

A efetividade das estratégias de prevenção da obesidade infantil : estudo de caso no concelho de Faro

RESUMO - A obesidade é um problema de saúde pública com dimensões alarmantes, motivo pelo qual foi classificada como uma das principais epidemias do século XXI. Estudos recentes demonstram que a prevalência da obesidade tem vindo a aumentar, sendo Portugal um dos países onde as taxas de prevalência são mais elevadas. No caso da obesidade infantil a situação também é muito preocupante. As crianças com excesso de peso ou obesas têm um risco acrescido de se tornarem adultos com doenças crónicas pelo que importa, desde cedo, desenvolver estratégias que permitam promover estilos de vida saudáveis e prevenir as várias doenças associadas. O desenvolvimento de intervenções durante a infância é considerado como uma das mais promissoras estratégias para a redução do excesso de peso e obesidade. Por outro lado, a escola é considerada como um dos locais mais atrativos e populares para se desenvolverem esses programas. Com este estudo pretendeu-se avaliar a intervenção realizada no concelho de Faro e verificar a sua efetividade no cumprimento dos objetivos definidos. A intervenção realizada em Faro, durante os anos letivos de 2007/2008 a 2010/2011, a 857 alunos do ensino básico, com idades compreendidas entre os 6 e os 10 anos de idade, teve como objetivos: avaliar e estabilizar a prevalência da obesidade infantil nas escolas do ensino básico do concelho de Faro, no ano letivo de 2007/2008; avaliar a evolução da prevalência da obesidade infantil durante os anos letivos de 2007/2008 a 2010/2011; e desenvolver estratégias para a promoção, em meio escolar, de uma alimentação mais saudável durante a intervenção. Os resultados levam-nos a concluir que a prevalência do excesso de peso e obesidade (15,2% e 10,5%, respetivamente) continua a níveis muito preocupantes nas crianças, tendo as raparigas apresentado uma prevalência maior do que os rapazes. A avaliação dos alunos, acompanhados prospetivamente ao longo dos primeiros 3 anos de intervenção, demonstrou uma diminuição da prevalência da obesidade de 9,6% no ano inicial para 8,3% no 3.º ano, e uma subida da taxa de prevalência do excesso de peso de 12,9% para 21,0%. A avaliação deste tipo de intervenções, apesar de difícil realização, é importante para que se possam definir novas estratégias, novas metodologias e novos caminhos para combater a obesidade infantil.

Effects of a monetary union on a small peripheral country: Stabilization and competitiveness in Portugal

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Economics from the NOVA – School of Business and Economics

Popular music exhibitions in Portugal: practices of representation from 2007 to 2013

This thesis focuses on the representation of Popular Music in museums by mapping, analyzing, and characterizing its practices in Portugal at the beginning of the 21st century. Now that museums' ability to shape public discourse is acknowledged, the examination of popular music's discourses in museums is of the utmost importance for Ethnomusicology and Popular Music Studies as well as for Museum Studies. The concept of 'heritage' is at the heart of this processes. The study was designed with the aim of moving the exhibiting of popular music in museums forward through a qualitative inquiry of case studies. Data collection involved surveying pop-rock music exhibitions as a qualitative sampling of popular music exhibitions in Portugal from 2007 to 2013. Two of these exhibitions were selected as case studies: No Tempo do Gira-Discos: Um Percurso pela Produção Fonográfica Portuguesa at the Museu da Música in Lisbon in 2007 (also Faculdade de Letras, 2009), and A Magia do Vinil, a Música que Mudou a Sociedade at the Oficina da Cultura in Almada in 2008 (and several other venues, from 2009 to 2013). Two specific domains were observed: popular music exhibitions as instances of museum practice and museum professionals. The first domain encompasses analyzing the types of objects selected for exhibition; the interactive museum practices fostered by the exhibitions; the concepts and narratives used to address popular music discursively, as well as the interpretative practices they allow. The second domain, focuses museum professionals and curators of popular music exhibitions as members of a group, namely their goals, motivations and perspectives. The theoretical frameworks adopted were drawn from the fields of ethnomusicology, popular music studies, and museum studies. The written materials of the exhibitions were subjected of methods of discourse analysis methods. Semi-structured interviews with curators and museum professional were also conducted and analysed. From the museum studies perspective, the study research suggests that the practice adopted by popular music museums largely matches that of conventional museums. From the ethnomusicological and popular music studies stand point, the two case studies reveal two distinct conceptual worlds: the first exhibition, curated by an academic and an independent researcher, points to a mental configuration where popular music is explained through a framework of genres supported by different musical practices. Moreover, it is industry actors such as decision makers and gatekeepers that govern popular music, which implies that the visitors' romantic conception of the musician is to some extent dismantled; the second exhibition, curated by a record collector and specialist, is based on a more conventional process of the everyday historical speech that encodes a mismatch between “good” and “bad music”. Data generated by a survey shows that only one curator, in fact that of my first case study, has an academic background. The backgrounds of all the others are in some way similar to the curator of the second case study. Therefore, I conclude that the second case study best conveys the current practice of exhibiting Popular Music in Portugal.

How Does Cultural Context Stimulate Creativity: A study of African Musicians in Lisbon, Portugal

The 21st century bodes an interesting time for companies and individuals alike with an increased focus on using creativity as a way to stimulate innovation to create competitive advantage. Several studies have looked at how creativity is stimulated within a corporate environment or how creativity is stimulated by people in a specific place. This study aimed to look at how the contextual environment fosters creativity in individuals and groups. With the increase in popularity of African and world music In Europe over the last ten years it was decided that the context of Lisbon, Portugal be used with a specific focus on African musicians living there and working in the Lisbon music scene. It became apparent themes of Creative crossovers, Geographical Location, a dynamic environment, Entrepreneurial encouragement and the presence of open-minded and flexible individual were involved in Lisbon’s ability to foster and empower creative individuals.

Managing talent through developmental job experiences (DJE): The mediating role of DJE between HPWS and employees' outcomes

In the competitive landscape of the 21st century, effectively managing human capital in firms is considered to be a potential source of sustainable performance. Therefore, in this study, we tested the influence of high-performance work systems, as a talent management tool, on employees’ experience of developmental jobs. Then, we tested the mediating effect of such experiences on employees’ engagement, exhaustion, performance and turnover intention. With a sample of 254 employees of a diversity of companies and sectors of activity, our findings demonstrated that high-performance practices increase engagement, via the promotion of developmental experiences of fit, which improves performance and decreases turnover intention. Besides, those practices do not control for the pressure dimension of the developmental job experiences that increases exhaustion and turnover intention despite not worsening performance.

The role of s-nitrosothiols and rho-kinase 1 in glucose and lipid metabolism

RESUMO: Na sociedade contemporânea a diabetes tipo 2 e a obesidade estão a aumentar exponencialmente, representando um grave problema de saúde pública. De acordo com a IDF “A diabetes e a obesidade são o principal problema de saúde pública do século XXI’. Para além destas duas patologias, a prevalência de esteatose hepática não-alcoólica (NAFLD), entre a população obesa e diabética, é de cerca de 90%. O aumento da obesidade, diabetes e NAFLD tem uma forte correlação com o aumento do consumo de gorduras e açúcares, acompanhado de um decréscimo acentuado da actividade física. A obesidade, diabetes e NAFLD tem sido escrupolosamente investigada mas as terapêuticas disponíveis continuam a ser muito limitadas. Tendo em conta o número crescente e alarmante de obesos e diabéticos o conhecimento detalhado da patofisiologia da obesidade, diabetes e NAFLD, tendo em vista a necessidade extrema de desenvolvimento de novas estratégias terapêuticas, é da mais elevada urgência. O fígado é reconhecido como um orgão primordial no controlo da homeostase. No estado pós-prandial, o fígado converte a glucose em glicogénio e lípidos. Em contraste, no estado de jejum, o fígado promove a produção de glucose. Sistemas neuronais e hormonais, bem como o estado metabólico do fígado, controlam de forma muito precisa a alternância entre os diferentes substratos metabólicos, dependente do estado prandial. A insulina tem um papel central no controlo do metabolismo energético no fígado; se, por um lado, inibe a produção hepática de glucose e corpos cetónicos, por outro, promove a glicólise e a lipogénese. O metabolismo energético no fígado é também regulado por vários factores de transcrição e co-reguladores que, por sua vez, são regulados pela insulina, glucagina e outras hormonas metabólicas. Em conjunto, todos estes factores e reguladores vão controlar de forma muito estreita a gluconeogénese, a β-oxidação e a lipogénese, no fígado. Para além dos já conhecidos reguladores do metabolismo hepático, novas moléculas têm sido estudadas como tendo um papel fundamental na regulação do metabolismo energético no fígado. Qualquer desequilíbrio no metabolismo hepático vai contribuir para a insulino-resistência, NAFLD e diabetes tipo 2. O principal objectivo do trabalho de investigação aqui apresentado é o contributo para o estudo detalhado da patogénese da diabetes e obesidade, num contexto de dietas ricas em açúcares e gorduras, e com a perspectiva de explorar novas estratégias terapêuticas. Os objectivos específicos deste trabalho eram: primeiro, determinar se o tratamento com glutationo (GSH) e óxido nítrico (NO) era suficiente para melhorar a insulino-resistência associada ao elevado consumo de sacarose; segundo, determinar o papel da Rho-kinase 1 (ROCK1) na regulação do metabolismo hepático da glucose e dos lípidos; e terceiro, estudar o efeito do metilsulfonilmetano (MSM) em doenças metabólicas associadas à obesidade. Na primeira parte deste trabalho de investigação foram utilizados ratos Wistar machos sujeitos a uma dieta rica em sacarose (HS). Tal como esperado, estes animais apresentavam insulino-resistência e hiperinsulinémia. A dieta HS levou ao aumento dos níveis hepáticos de NO e ao decréscimo dos níveis de GSH no fígado. Em jejum, a administração intraportal de GSH e NO, a animais saudáveis promoveu um aumento significativo da sensibilidade à insulina. Também nestes animais, a administração intravenosa de S-nitrosotióis, compostos orgânicos que contém um grupo nitroso acoplado a um átomo de enxofre de um tiol, promoveu o aumento significativo da sensibilidade à insulina. Pelo contrário, em animais sujeitos à dieta HS, as doses padrão de GSH + NO e de S-nitrosotióis não conseguiram promover o aumento da sensibilidade à insulina. No entanto, ao aumentar a dose de S-nitrosotióis administrados por via intravenosa, foi possível observar o aumento da sensibilidade à insulina dependente da dose, indicando um possível papel dos S-nitrosotióis como sensibilizadores de insulina. O estudo detalhado do papel dos S-nitrosotióis na via de sinalização da insulina revelou que há um aumento da fosforilação do receptor da insulina (IR) e da proteína cinase B (Akt), sugerindo um efeito dos S-nitrosotióis nesta via de sinalização. Os resultados apresentados nesta primeira parte sugerem que os S-nitrosotióis promovem a correcta acção da insulina, podendo vir a ser importantes alvos terapêuticos. Na segunda parte deste trabalho de investigação utilizámos murganhos, com uma delecção específica da ROCK1 no fígado, e sujeitos a uma dieta rica em lípidos (HFD). Foi possível concluir que a ausência da ROCK1 no fígado previne a obesidade, melhora a sensibilidade à insulina e protege contra a esteatose hepática. A ausência de ROCK1 no fígado levou a um decréscimo significativo da expressão génica de genes associados à lipogénese, com uma diminuição acentuada do fluxo metabólico associado a esta via. Pelo contrário, a sobreexpressão de ROCK1, exclusivamente no fígado, promove a insulino-resistência e a esteatose hepática no contexto de obesidade induzida pela dieta. Para além disto, a delecção da ROCK1 no fígado de animais obesos e diabéticos, os murganhos deficientes em leptina, corroborou os dados obtidos no primeiro modelo animal, com a franca melhoria da hiperglicémia, hiperinsulinémia e esteatose hepática. Os dados que compõem esta parte do trabalho de investigação sugerem que a ROCK1 tem um papel crucial na regulação do metabolismo lipídico. Na terceira e última parte deste trabalho de investigação foi investigado o efeito do composto metilsulfunilmetano (MSM), um composto organosulfúrico naturalmente presente em plantas e utilizado também como suplemento dietético, em murganhos obesos e insulino-resistentes, por exposição a uma dieta rica em lípidos (DIO). O tratamento com MSM melhorou a insulino-resistência e protegeu contra a esteatose hepática. O conteúdo hepático em triglicéridos e colesterol também diminuíu de forma significativa nos animais DIO sujeitos ao tratamento com MSM, bem como a expressão génica associada à lipogénese. Para além disto, o tratamento com MSM levou a uma diminuição da expressão génica associada à inflamação. De realçar que o tratamento com MSM levou a uma melhoria do perfil hematopoiético destes animais, tanto na medula óssea como no sangue. Para comprovar o efeito benéfico do MSM na obesidade e insulino-resistência utilizámos murganhos deficientes no receptor da leptina, e por isso obesos e diabéticos, tendo observado um perfil semelhante ao obtido para murganhos sujeitos a uma dieta rica em lípidos e tratados com MSM. Concluímos, através dos dados recolhidos, que o MSM como suplemento pode ter efeitos benéficos na hiperinsulinémia, insulino-resistência e inflamação que caracterizam a diabetes tipo 2. Em resumo, os dados obtidos neste trabalho de investigação mostram que os S-nitrosotióis podem ter um papel importante como sensibilizadores da insulina, promovendo um aumento da sensibilidade à insulina num contexto de dietas ricas em sacarose. Para além disto, estudos in vitro, sugerem que os S-nitrosotióis regulam, especificamente, a via de sinalização da insulina. Este trabalho teve também como objectivo o estudo da ROCK1 como regulador do metabolismo da glucose e dos lípidos no fígado. Através do estudo de animais com uma delecção ou uma sobreexpressão da ROCK1 no fígado mostrou-se que esta tem um papel crucial na patogénese da obesidade e diabetes tipo 2, especificamente através do controlo da lipogénese de novo. Finalmente, foi também objectivo deste trabalho, explorar o efeito do MSM em animais DIO e deficientes em leptina. O tratamento com MSM protege de forma evidente contra a obesidade e insulino-resistência, com especial enfâse para a capacidade que esta molécula demonstrou ter na protecção contra a inflamação. Em conjunto os vários estudos aqui apresentados mostram que tanto os S-nitrosotióis como a ROCK1 têm um papel na patogénese da obesidade e diabetes tipo 2 e que a utilização de MSM como suplemento às terapêuticas convencionais pode ter um papel no tratamentos de doenças metabólicas.-------------------------------ABSTRACT: In modern western societies type 2 diabetes and obesity are increasing exponentially, representing a somber public concern. According to the International Diabetes Federation (IDF) ‘Diabetes and Obesity are the biggest public health challenges of the 21st century’. Aside from these the prevalence of nonalcoholic fatty liver disease (NAFLD), among the diabetic and obese population, is as high as 90%. It is now well established that the increase in obesity, diabetes and NAFLD strongly correlates with an increase in fat and sugar intake in our diet, alongside physical inactivity. The pathogenesis of obesity, diabetes and NAFLD has been thoroughly studied but the treatment options available are still narrow. Considering the alarming number in the obese and diabetic population the complete understanding of the pathogenesis, keeping in mind that new therapeutic strategies need to be attained, is of the highest urgency. The liver has been well established as a fundamental organ in regulating whole-body homeostasis. In the fed state the liver converts the glucose into glycogen and lipids. Conversely, in the fasted state, glucose will be produced in the liver. Neuronal and hormonal systems, as well as the hepatic metabolic states, tightly control the fast to fed switch in metabolic fuels. Insulin has a central role in controlling hepatic energy metabolism, by suppressing glucose production and ketogenesis, while stimulating glycolysis and lipogenesis. Liver energy metabolism is also regulated by various transcription factors and coregulators that are, in turn, regulated by insulin, glucagon and other metabolic hormones. Together, these regulators will act to control gluconeogenesis, β-oxidation and lipogenesis in the liver. Aside from the well-established regulators of liver energy metabolism new molecules are being studied has having a role in regulating hepatic metabolism. Any imbalance in the liver energy metabolism is a major contributor to insulin resistance, NAFLD and type 2 diabetes. The overall goal of this research work was to contribute to the understanding of the pathogenesis of diabetes and obesity, on a setting of high-sucrose and high-fat diets, and to explore potential therapeutic options. The specific aims were: first, to determine if treatment with glutathione (GSH) and nitric oxide (NO) was sufficient to ameliorate insulin resistance induced by high-sucrose feeding; second, to determine the physiological role of rho-kinase 1 (ROCK1) in regulating hepatic and lipid metabolism; and third, to study the effect of methylsulfonylmethane (MSM) on obesity-linked metabolic disorders. In the first part of this research work we used male Wistar rats fed a high-sucrose (HS) diet. As expected, rats fed a HS diet were insulin resistant and hyperinsulinemic. HS feeding increased hepatic levels of NO, while decreasing GSH. In fasted healthy animals administration of both GSH and NO, to the liver, was able to increase insulin sensitivity. Intravenous administration of S-nitrosothiols, organic compounds containing a nitroso group attached to the sulfur atom of a thiol, in fasted control animals also increased insulin sensitivity. Under HS feeding the standard doses of GSH + NO and S-nitrosothiols were unable to promote an increase in insulin sensitivity. However, the intravenous administration of increasing concentrations of S-nitrosothiols was able to restore insulin sensitivity, suggesting that S-nitrosothiols have an insulin sensitizing effect. Investigation of the effect of S-nitrosothiols on the insulin signaling pathway showed increased phosphorylation of the insulin receptor (IR) and protein kinase B (Akt), suggesting that S-nitrosothiols may have an effect on the insulin signaling pathway. Together, these data showed that S-nitrosothiols promote normal insulin action, suggesting that they may act as potential pharmacological tools. In the second part of this research work we used liver-specific ROCK1 knockout mice fed a high-fat (HF) diet. Liver-specific deletion of ROCK1 prevented obesity, improved insulin sensitivity and protected against hepatic steatosis. Deficiency of ROCK1 in the liver caused a significant decrease in the gene expression of lipogenesis associated gene, ultimately leading to decreased lipogenesis. Contrariwise, ROCK1 overexpression in the liver promoted insulin resistance and hepatic steatosis in diet-induced obesity. Furthermore, liver-specific deletion of ROCK1 in obese and diabetic mice, the leptin-deficient mice, improved the typical hyperglycemia, hyperinsulinemia and liver steatosis. Together, these data identify ROCK1 as a crucial regulator of lipid metabolism. In the third and final part of this research work we investigated the effect of MSM, an organosulfur compound naturally found in plants and used as a dietary supplement, on diet-induced obese (DIO) and insulin resistant mice. MSM treatment ameliorated insulin resistance and protected against hepatosteatosis. Hepatic content in triglycerides and cholesterol was significantly decreased by MSM treatment, as well as lipogenesis associated gene expression. Furthermore, MSM treated mice had decreased inflammation associated gene expression in the liver. Importantly, FACS analysis showed that MSM treatment rescued the inflammatory hematopoietic phenotype of DIO mice in the bone marrow and the peripheral blood. Moreover, MSM treatment of the obese and diabetic mice, the leptin-deficient mice, resulted in similar effects as the ones observed for DIO mice. Collectively, these data suggest that MSM supplementation has a beneficial effect on hyperinsulinemia, insulin resistance and inflammation, which are often found in type 2 diabetes. In conclusion, this research work showed that S-nitrosothiols may play a role as insulin sensitizers, restoring insulin sensitivity in a setting of high-sucrose induced insulin resistance. Furthermore, in vitro studies suggest that S-nitrosothiols specifically regulate the insulin signaling pathway. This research work also investigated the role of hepatic ROCK1 in regulation of glucose and lipid metabolism. Using liver-specific ROCK 1 knockout and ROCK1 overexpressing mice it was shown that ROCK1 plays a role in the pathogenesis of obesity and type 2 diabetes, specifically through regulation of the de novo lipogenesis pathway. Finally, this research work aimed to explore the effect of MSM in DIO and leptin receptor-deficient mice. MSM strongly protects against obesity and insulin resistance, moreover showed a robust ability to decrease inflammation. Together, the individual studies that compose this dissertation showed that S-nitrosothiols and ROCK1 play a role in the pathogenesis of obesity and type 2 diabetes and that MSM supplementation may have a role in the treatment of metabolic disorders.

How small accounting firms can compete in an environment in which the big four are getting bigger

This paper sets out to determine how small accounting firms can compete in the United States in the early 21st century. The first chapter identifies the central goal of the paper: namely, to use existing literature and market data to define a business strategy for Ross & Moncure, Inc., a small accounting firm in the metropolitan Washington area. The second chapter is a literature review, and in it the author finds that large accounting firms are advantaged in terms of reputation, ability to diversify, and ability to retain employees, but are disadvantaged in their ability to form longstanding successful relationships with clients. In the third chapter, the author explores the relationship between the Big Four firms and their employees. The goal of this chapter is to determine how small accounting firms can compete for top talent in the HR market, and the author finds that this can be done by offering faster career progression and more client interaction. The fourth chapter looks at the market for accounting services in the United States, exploring the different options that consumers have to meet their accounting needs. It is found in this chapter that big and small accounting firms tend to compete for clients of different profiles. In the fifth chapter, the author uses proprietary company data to explore the composition, existing strategy and culture of Ross & Moncure. In the sixth chapter, all of the previous chapters come together to formulate a strategy and plan for action for Ross & Moncure: specifically, that the firm should further cultivate networks and relationships, and should create a fulfilling professional environment by increasing client-employee interaction, encouraging external education, and allowing employees to take on many different projects