Obesity is a disease that increases risk of developing metabolic diseases including insulin resistance (IR), metabolic syndrome (MS), and type 2 diabetes (T2D). Adipose tissue expansion during obesity leads to immune cell infiltration, causing local inflammation and disruption of lipid homeostasis. There is an association between exposure to environmental chemicals, like p,p’-DDE, a metabolite of p,p’-DDT, and diagnosis of obesity, dyslipidemia, IR, and prevalence of MS and T2D. DDE accumulates in fatty tissues and has been shown to have immunomodulatory properties, affecting macrophage and T cell populations. Potential mechanisms were studied by which DDE could modulate adipocyte and immune cell function and facilitate an increased risk of obesity and immune dysregulation, potentially through cyclooxygenase-2 (COX-2). 3T3-L1 preadipocytes and J774A.1 macrophages were studied for the effects of DDE on adipogenesis and macrophage reactivity, respectively. 3T3-L1 cells were induced to differentiate to adipocytes using a sub-optimal differentiation cocktail with increasing concentrations of DDE (0.5uM-100uM). It was determined that DDE enhanced adipogenesis in a concentration dependent manner and the expression of adipogenic and lipogenic genes, indicating that DDE enhances adipogenesis. In J774A.1 cells, the ability of DDE or 10uM NS-398, a specific COX-2 inhibitor, to inhibit the production of the prostaglandins PGE2, PGD2, PGF2a, was assessed in vitro and in a cellree system. DDE or NS-398 followed by immune challenge reduced cellular PG secretion and reduced PG production in a cell free system, indicating that DDE may interfere with lipid mediator signaling. Additionally, DDE or NS-398 exposure altered gene expression in J774A.1 cells following M1 or M2 polarization stimulus. Lastly, male C57Bl mice were exposed to 2mg/kg DDE for 5 days and the macrophage population of the adipose stromal vascular fraction was analyzed by flow cytometry. Adipose from DDE treated animals contained approximately 40% F4/80+CD11b+ macrophages. These results indicate that DDE may alter the homeostasis of adipose tissue by both enhancing adipogenesis and altering the reactivity of the resident macrophage population in a manner that may contribute to adipose dysfunction. These data suggest a possible mechanism by which DDE exposure may contribute to adiposity and adipose tissue dysfunction commonly seen in metabolic disease.

Type 2 diabetes mellitus (T2DM) is classified as a metabolic disorder characterized by hyperglycemia that results from defects in insulin action and/or secretion, and currently affects 8.3% of the US population according to the CDC’s 2011 National Diabetes Fact Sheet. Several contributing factors have been identified to development of this disease. Published evidence indicates type 2 diabetes mellitus (T2DM) patients display lower overall paraoxonase activity and that this may be partially due to genetic variations in the paraoxonase-1 (PON-1) gene. Some bioaccumulative organochlorine (OC) pesticides have been shown to contribute to increased T2DM prevalence. In addition, these OC compound levels have been associated with alterations in adipocyte cytokine levels as well as increased inflammatory markers. Three hundred blood samples with clinical and demographic information were obtained from two US Air Force hospitals. A total of 151 non-diabetics and 149 T2DM subjects were evaluated for PON-1 activity, PON-1 Q192R and L55M genetic polymorphisms, OC compound concentrations, inflammatory marker levels and adipokine concentrations. PON-1 activity, using diazoxon as the substrate, was decreased in the T2DM subjects. Some of the PON-1 genetic polymorphisms tested were also associated with decreased PON-1 activity. OC compound levels were increased in the T2DM subjects. The non-diabetic subjects possessing elevated DDE and trans-nonachlor were associated with increased inflammation, a common hallmark of early T2DM development. Additionally, elevated OC levels were seen in association with altered adipokine concentrations. Overall, a decrease in the antioxidant properties of PON-1 as well as factors contributing to chronic low level inflammation such as elevated OC plasma concentration appear to be significant contributors to T2DM prevalence in the population studied.

Measuring transmembrane water exchange can provide potential biomarkers for tumors and brain disorders. Diffusion Magnetic Resonance Imaging (dMRI) is a well-established tool that can non-invasively measure water exchange across cell membranes. Diffusion Exchange Spectroscopy (DEXSY) is one of the dMRI-based frameworks used to estimate exchange. DEXSY provides a detailed picture of multi-site exchange processes but requires a large quantity of data. Several models based on the DEXSY framework have been proposed to reduce the acquisition time. Filter Exchange Imaging (FEXI) and curvature models are two of them that only require certain samples of the DEXSY dataset. Diffusion-Exchange Weighted (DEW) Imaging model is another data reduction method accounting for restricted diffusion within cells and can use a specific subset of the DEXSY dataset to measure exchange. Furthermore, a more general expression of the DEXSY signal, referred to as the general model, can theoretically analyze the full space or reduced DEXSY datasets and estimate exchange. However, the results of the subsampling schemes and the data reduction models have not been compared to the full space estimation.  Therefore, this thesis aims to experimentally explore the feasibility of estimating exchange using these four models (the general, FEXI, curvature and DEW models) with the data acquired using a low-field benchtop MR scanner, and compare the estimates from the general model with different subsampling schemes and the data reduction models to the full space estimation. For this purpose, a double diffusion encoding (DDE) sequence was modified from an existing sequence on the benchtop MR scanner and a DEXSY experiment was conducted on this MR scanner and a yeast phantom to acquire a full space dataset. The exchange parameters estimated from the full space dataset using the general model were used as "ground truths" to evaluate the estimates from the reduced datasets analyzed using the general, FEXI and curvature models. Moreover, two alternative subsampling schemes named the shifted DEW and new trajectory schemes were proposed and employed to measure exchange. The results indicate that all the methods except the curvature sampling scheme employed with both the general and curvature models provided comparable estimates to the "ground truths". The shifted DEW and new trajectory sampling schemes performed better over others in terms of consistency with the "ground truths" and low variations between voxels, suggesting the theoretical and experimental optimization of these two subsampling schemes can be further studied and developed.

<p>The shallow soils of a former orchard area in Point Pelee National Park, near Leamington, Ontario, Canada have elevated concentrations of chlorinated pesticides above the regulatory limits. Previous studies in this area have shown that the DDT, DOE and ODD are highly persistent with an estimated half-life of DDT in the range of 15-30 years. In 2002 a pilot-scale field remediation experiment involving the application of cyclodextrin was conducted. This experiment resulted in substantial decrease of DDT, DDE and DDD concentrations in the upper soil layer within the remediation grid. Soil samples were collected within the treatment plots a year after the cyclodextrin application was completed to assess any further changes in concentrations of DDT, DDE and DDD. Groundwater samples were collected in the vicinity of the soil remediation grid which provided DDT, DDE and DDD concentrations in groundwater to assess the vertical mobilization of the compounds. Mass balance of the "soil - groundwater" system was calculated in order to estimate the degradation rate of DDT within the remediation zone. The 2-D unsaturated/saturated flow and solute transport numerical model "HYDRUS 2-D" was used to gain a better estimation of DDT, DDE and DDD mass and distribution in groundwater. The effectiveness of cyclodextrin application for remediation of DDT contaminated soils was assessed. After remediation treatments had stopped, there was no indication of further degradation of DDT and its metabolites in the upper layer of soil. The groundwater concentration of DDT, DDE and DDD near the remediation grid was 10-100 times higher than background value. This increase in groundwater concentration is a direct indication of DDT, DDE and DDD mobilization by cyclodextrin. The estimates of total mass of DDT in groundwater are less than 1% of mass leached from the soil. It was concluded that the application of cyclodextrin promoted enhanced co-metabolic biodegradation of DDT and it metabolites DDE and DDD. The estimated half-life for the displaced DDT was less than 2 months. This work demonstrates that cyclodextrin can be a highly effective agent for remediation of DDT contaminated soils.<p> / Thesis / Master of Science (MSc)

No description available.

L'hexaclorobenzè (HCB) és un compost organoclorat àmpliament distribuït per tot el planeta, altament lipofílic que s'acumula als sistemes biològics. Els nounats s'exposen a aquests compostos organoclorats (OCs) a través de la placenta i de la lactància materna. Tot i que l'HCB és un dels OCs més comuns, la seva transferència a través de la placenta de la mare al fetus durant la gestació i a través de l'alletament matern està poc documentada. El coneixement sobre els seus possibles efectes sobre la salut infantil és també bastant limitat. A Flix, un poble de la Ribera d'Ebre, es van detectar nivells molt elevats d'HCB a l'atmosfera degut a la seva proximitat a una empresa electroquímica. Els objectius del present treball són els d'avaluar l'exposició a OCs a través de la placenta i de la lactància materna i els seus efectes sobre la salut infantil durant el primer any de vida en el conjunt de nounats d'aquesta població. / Hexachlorobenzene (HCB) is an organochlorine compound widely spread in the environment, highly lipophyilic which accumulates in all biological systems. Newborns are exposed to organochlorine compounds (OCs) through placenta and via breastfeeding. Although HCB is one of the most common OCs, its transference from the mother to the child through placenta and via breastfeeding is poorly documented. The knowledgement of the possible adverse effects on infant's health is also limited. In Flix, a small village in the Ribera d'Ebre area, high levels of HCB were detected in the atmosphere of the village due to the vicinity of an electrochemical factory. The objectives of the present study are to evaluate OCS exposition through placenta and breastfeeding and its effects on infant's health during the first year of life.

[pt] A terceirização de atividades de apoio à administração pública, no Brasil, toma impulso na atualidade através das reformas neoliberais do aparelho do Estado, como veículo de racionalização de recursos públicos. Mas, ao extrapolar os limites de sua função institucional auxiliar, tornando-se artifício de ocupação privada e precária de competências estatais, a prática enseja graves repercussões deletérias sobre relevantes valores constitucionais referidos a princípios republicanos e relacionados à proteção dos direitos fundamentais dos trabalhadores. Traçando os caminhos evolutivos a partir da sua gênese na iniciativa privada, o presente estudo buscará captar a conflituosidade imanente ao movimento de terceirização, perquirindo o modo como o Direito tem traduzido a tensa relação entre os fundamentos de legitimidade e as repercussões deletérias da prática sobre os interesses da sociedade. Na argumentação jurisprudencial sobre a questão, especialmente no âmbito da Justiça do Trabalho, será identificada uma lógica de ponderação de interesses que permeia sua interpretação. O objetivo central da pesquisa é alcançado com a proposição de uma leitura jurídica interdisciplinar do fenômeno, sob a perspectiva da nova hermenêutica constitucional pós- positivista, visando auxiliar a construção teórica de soluções normativas que delimitem os espaços legítimos da terceirização no serviço público, à luz da proporcionalidade. Propugna-se, assim, pela máxima concretização dos princípios constitucionais referidos à matéria: a eficiência administrativa, os princípios republicanos e a proteção dos direitos fundamentais dos trabalhadores terceirizados. Trata-se, portanto, de um estudo intradogmático, comprometido com respostas interpretativamente construídas no espaço dialógico entre o Direito e a moral, e inspirado na efetividade e na unidade da Constituição. / [es] La subcontratación de actividades de apoyo a la administración pública, en Brasil, toma impulso, en la actualidad, en las reformas neoliberales del aparato del Estado, como vehículo de racionalización de recursos públicos. Pero, al ultrapasar los límites de su función institucional auxiliar, tornándose artificio de ocupación privada y precaria de habilidades estatales, la práctica espera la oportunidad de graves repercusiones deletéreas sobre relevantes valores constitucionales referidos a principios republicanos y relacionados a la protección de los derechos fundamentales de los trabajadores. Delineando sus caminos evolutivos a partir de su génesis en la iniciativa privada, el presente estudio buscará captar el conflicto inherente al movimiento de subcontratación, investigando el modo como el Derecho ha traducido la tensa relación entre los fundamentos de la legitimidad y las repercusiones deletéreas de la práctica sobre los intereses de la sociedad. En la argumentación jurisprudencial sobre la cuestión, especialmente en el ámbito de la Justicia del Trabajo, será identificada una lógica de ponderación de intereses que transmite su interpretación. El objetivo central de la investigación es alcanzado con la proposición de una lectura jurídica interdisciplinar del fenómeno, bajo la perspectiva de la nueva hermenéutica constitucional pos- positivista, pretendiendo auxiliar la construcción teórica de soluciones normativas delimitadoras de los espacios legítimos de la subcontratación en el servicio público, a la luz de la proporcionalidad, con máxima concretización de los principios constitucionales referidos a la materia: la eficiencia administrativa, los principios republicanos y la protección de los derechos sociales de los trabajadores subcontratados. Se trata, por lo tanto, de un estudio intra-dogmático, comprometido con respuestas interpretativamente construidas en el espacio del diálogo entre el Derecho y la moral, e inspirado en la afectividad y en la unidad de la Constitución.

Se analiza la responsabilidad social empresarial (RSE) como medio eficaz para reducir costos y fortalecer la cuota de mercado, tomando como caso. la banca comercial de Perú y Brasil, y  aspectos relacionados con la implementación de acciones concretas vinculadas a la atención de las necesidades de los consumidores, con el compromiso de los derechos laborales y con la protección medio ambiental; Sobre la base de los resultados, se puede concluir que ninguno de los casos peruanos presentaron acciones que permitan clasificarlos en un nivel regular de avance, mientras que en Brasil dos casos se destacan: ABN Amro Real y Bradesco. Asimismo, entre 2007 y 2009, en las instituciones financieras peruanas se ha avanzado muy poco en cuanto a la implementación de políticas que impliquen acciones permanentes de medio ambiente y atención a consumidores y trabajadores, aunque  se ha podido observar mejorías en este período en Interbank y el Banco de Crédito del Perú.

RESUMENEscenarios como una deficiente asignación de riesgos o conductas oportunistas de los postores, enfrentan al gobierno a la presión de modificar contratos de Asociación Público-Privada, al poco tiempo de haber sido adjudicados, bajo la justificación se requerirse precisiones para su financiamiento. En estas denominadas “adendas de bancabilidad”, el peligro de trasladar el riesgo de financiamiento y que se reduzca el beneficio esperado del proyecto para el Estado es alto, pudiendo llegar incluso a cuestionar la legitimidad del propio esquema de Asociación Público-Privada. Nuestra propuesta a esta problemática es la aplicación general de la técnica del Project Finance al desarrollo de estos proyectos. En primer lugar, porque el trabajo de debida diligencia para la evaluación de viabilidad del proyecto, característico del Project Finance, garantizaría que lleguen para adjudicación sólo aquellos proyectos que sean técnica, económica y financieramente viables, y, por ende, capaces de atraer el interés de los prestamistas en el mercado, eliminando con ello la necesidad de suscribir posteriomente adendas de bancabilidad. En segundo lugar, porque al tratarse de una técnica de financiamiento basada en la capacidad del proyecto de generar flujos de caja futuros, el Project Finance mitigaría además el riesgo de compleción de la obra y puesta en operación de la infraestructura, en tanto que la evaluación para el financiamiento se enfocará en la realización de los flujos una vez que el proyecto esté en funcionamiento, esto es, cuando el servicio esté siendo efectivamente prestado a los usuarios, lo que constituye el fin último del Estado para la promoción de estos proyectos. Ello, claramente implicará la eliminación de cualquier mecanismo de pago antes del inicio de operación del proyecto. Así, el Project Finance es la forma de financiamiento que realmente aseguraría al Estado el beneficio esperado de implementar los proyectos de inversión bajo la modalidad de Asociaciones Público-Privadas

La presente investigación propone un grupo de conductores con sus respectivos criterios, adaptados de la Norma Técnica para la Gestión de la Calidad de Servicios en el Sector Público, que responden a generar calidad de servicios para los ciudadanos en los trámites digitales gubernamentales. Esta propuesta se construye en función a un proceso de análisis de literatura, la Norma Técnica para la Gestión de la Calidad de Servicios en el Sector Público y la validación de especialistas y ciudadanos. El enfoque metodológico del presente trabajo es de tipo cualitativo, con alcance exploratorio. Este inicia con el análisis de herramientas internacionales de medición de calidad de servicios digitales gubernamentales. Estas al ser contrastadas se obtuvo un modelo común de conductores y criterios que pasan a ser comparadas con la Norma Técnica para la Gestión de la Calidad de Servicios en el Sector Público. Obteniendo como resultado un primer grupo de variables con sus respectivas sub-variables. Este proceso se complementa con la validación de especialistas y ciudadanos usuarios, los cuales evaluarán la validez de la adaptación de los conductores propuestos para los servicios digitales gubernamentales, así como, la incorporación de un conductor a partir de los resultados. Finalmente, como consecuencia de lo antes mencionado, se propone 7 conductores que inciden en la satisfacción del ciudadano en el uso de servicios digitales públicos, de los cuales 6 se forman de la adaptación de sus criterios y solo uno es propuesto y no vinculado con la Norma Técnica para la Gestión de la Calidad de Servicios en el Sector Público.