Bioactive food components containing n-3 polyunsaturated fatty acids (PUFA) and curcumin modulate multiple determinants that link inflammation to cancer initiation and progression. In this dissertation, both transgenic and dietary mouse models were used to elucidate the effect of n-3 PUFA and curcumin treatment on murine intestinal inflammation. Specifically, fat-1 transgenic mice, which convert endogenous n-6 PUFA to n-3 PUFA in multiple tissues, exhibited a reduced number of colonic adenocarcinomas per mouse (1.05 plus/minus 0.29 versus 2.12 plus/minus 0.51, P = 0.033), elevated apoptosis (P = 0.03), and a decrease in n-6 PUFA–derived eicosanoids compared with wild-type (wt) mice in an azoxymethane (AOM) - dextran sodium sulfate (DSS) model. Following a 2-week recovery period after 5 days of DSS exposure, colonic inflammation and ulceration scores returned to pretreatment levels only in fat-1 mice. In addition, fat-1 vs wt mice exhibited decreased (P < 0.05) levels of CD3 , CD4 T helper, and macrophage cell numbers in the colon. The ability of n-3 PUFA to favorably modulate the resolution of intestinal inflammation in fat-1 mice was linked to an enhancement (P < 0.05) in the percentage of colonic lamina propria (cLP) CD4 FoxP3 cells and a decrease in both splenic and cLP Th17 cells (0.8 vs 1.2 percent in spleen, 1.4 vs 1.7 percent in colon) (P < 0.05) in fat-1 mice compared to wt. These results suggest that the antitumorigenic effect of n-3 PUFA may be mediated via its anti-inflammatory properties. The combined effect of n-3 PUFA and curcumin on DSS induced colitis was assessed in C57BL/6 mice. Addition of fish oil (FO) and/or curcumin to a corn oil (CO) based diet increased animal mortality compared to CO alone (P < 0.05). Consistently, following 1 or 2 cycles of DSS treatment, both dietary FO and curcumin promoted mucosal injury/ulceration compared to CO. However, compared to other diets, FO and curcumin combined feeding enhanced the resolution of chronic inflammation and suppressed (p < 0.05) a key inflammatory mediator, NF-kB, in colon mucosa. Mucosal microarray analysis revealed that dietary FO and curcumin differentially modulated the expression of genes induced by DSS treatment. These results suggest that dietary lipids and curcumin interact to regulate mucosal homeostasis and the resolution of chronic inflammation in the colon.

Sorghum contains many phenolic compounds which have potential antioxidant, anti-inflammatory, and chemopreventive properties as well as natural colorants in foods. Phenolic compounds of stalks, sheaths, leaves, glumes and grains from tan (ARTx631/RTx436), red (Tx2911) and purple (Tx3362) sorghum plants were characterized by UPLC-MS/MS. Antiproliferative properties of selected sorghum extracts were evaluated using HT-29 colon cancer cells and absorption of their polyphenolics was determined by a Caco-2 in vitro model system. Phenolic acids, flavones, 3-deoxyanthocyanidins and chalcones were found in all plant components. Phenolic acids were predominant in the stalks, sheaths and grains of all sorghum types. Flavone glycosides were predominant in leaves, sheaths and stalks while flavone aglycones in glumes and grains. 3-Deoxyanthocyanidins and chalcones were mostly found in sheaths, leaves, glumes and grains of Tx2911 (red) and Tx3362 (purple) genotypes. Sorghum leaves showed high levels of flavone glycosides while glumes had high levels of flavones aglycones. Glume extract of ATx631/RTx436 (tan) and Tx2911 genotypes had the strongest antiproliferation activity (IC_(50) = 85-178 µg/ml), these extracts had also the highest levels of flavone aglycones (19.6-49.8 mg/g). Absorption of flavones (30.4-42.3 %) was higher than 3-deoxyantocyanidins (1.4-11.3%), while absorption of methoxylated 3-deoxyanthocyanidins (11.3%) was higher than non-methoxylated 3-deoxyanthocyanidins (1.4 – 1.6 %). Flavones had high absorption compared to other sorghum phenolics suggesting that sorghum flavone aglycones are more bioavailable than other sorghum phenolic compounds. Consequently, sorghum glumes could be used as used as a source of phytochemicals to increase value of sorghum crop.

In block-selective solvent, the rod-coil block copolymers can form various micellar structures. With block copolymers that contain a conjugated polymer block, the conformation of the conjugated polymer can be reflected by spectral changes in the solution. Therefore, it is of interest to study the relationship between the spectral changes and the nature of the conjugated polymer. The fundamental physical properties of poly(3-hexyl thiophene) (P3HT) were studied. Five P3HT samples with different molecular weights were used. We have determined the relationship between physical and spectral properties of this polymer and its molecular weight. In particular, we have found that the refractive index increments, the maximum absorbance wavelength, extinction coefficients, and the emission wavelengths, increase with molecular weight. Diblock copolymers of poly(3-hexyl thiophene)-block-poly(2-hydroxyethyl methacrylate) (P3HT-b-PHEMA) were also studied. The morphological and spectral changes of these block copolymers were studied at various stages of micelle formation in block selective solvents. The relationship between the volume fraction of the P3HT block and their physical and spectral properties were also discussed. / Thesis (Master, Chemistry) -- Queen's University, 2010-03-31 11:30:44.539

A series of medium-chain-length poly(3-hydroxyalkanoates) (MCL-PHAs) with enriched 3-hydroxynonanoate (HN) content (up to 95.8 mol% compared to 68.6 mol% without acrylic acid) or 3-hydroxyoctanoate (HO) content (up to 97.5 mol% compared to 88.0 mol% without acrylic acid) was produced in continuous culture by co-feeding fatty acid and glucose plus inhibiting fatty acid β-oxidation using acrylic acid. Using a similar feeding strategy in fed-batch fermentation, similar monomeric compositions but a higher biomass concentration and PHA content could be obtained. However, at a lower growth rate (0.15 h-1 vs. 0.25 h-1), the biomass concentration and PHA content could be greatly enhanced from 17.1 to 71.4 g L-1 and from 64.4 to 75.5%, respectively, while the HN content decreased slightly from 92.2 to 88.9 mol%. PHAs produced under acrylic acid inhibition possessed improved physical properties including a higher melting point, faster crystallization rate, and greater tensile strength at break and Young’s modulus. Two recovery methods were developed for the recovery of MCL-PHA from Pseudomonas putida KT2440. One applied acetone extraction which was capable of recovering all the PHA from the cells with a purity of 91.6% and no detectable polymer molecular weight loss using Soxhlet extraction. Further purification was achieved by redissolving in acetone and reprecipitating in cold methanol. The other method used sodium hydroxide to solubilize the non-PHA cellular material. PHA purity of about 85% was obtained from a biomass containing 65.6% PHA after treatment with 0.2 N NaOH at 22 ± 1oC for 2 h or with 0.1 N at 80 ± 1oC for 15 min. However, a treatment at 22 ± 1oC followed by a second NaOH treatment at 80 ± 1oC resulted in higher PHA purity (94.7%) with a recovery efficiency of 88%. Under these conditions, NaOH digestion had a negligible effect on PHA molecular weight. / Thesis (Ph.D, Chemical Engineering) -- Queen's University, 2010-08-30 22:44:44.501

No description available.

No description available.

No description available.

Se parte de la premisa de identificar las vulnerabilidades sociales y los procesos de exclusión de los adolescentes en conflicto con la ley, para establecer la relación entre la vulnerabilidad y la generación de trayectorias delictivas, así como su tratamiento en el escenario y su proyección al itinerario. Para dotar de coherencia este trabajo y facilitar el seguimiento de la argumentación se ha optado por dividirlo en tres partes: La primera parte comprende del capítulo primero al quinto, y concreta los fundamentos teóricos. Se inicia con la explicación del paradigma de la vulnerabilidad y exclusión social como telón de fondo del objeto investigado; continúa con las referencias históricas,pues hallamos que conceptos y prácticas actuales provienen del pasado y sencillamente se han adaptado en el devenir de los tiempos; prosigue con una incursión a las teorías sociológicas de la delincuencia juvenil para fijar posiciones en el origen social, remarcar su complejidad y dificultades de conceptualización. Asimismo, se analizan los modelos de tratamiento pues decantarse por uno o por otro es una opción de política criminal relacionada con el modelo de justicia juvenil y con la concepción del delito y la delincuencia de una sociedad. Se explora el marco jurídico español, su evolución, sus debates y sus orientaciones, así como el encaje en el ordenamiento internacional. Se finaliza con una revisión de las investigaciones realizadas en España y en la Comunitat Valenciana sobre los adolescentes en conflicto con la ley, desde una perspectiva integral, es decir, que incorporen en sus análisis lo social y lo jurídico. La segunda parte abarca del capítulo sexto al undécimo, donde se incluye los fundamentos metodológicos y el análisis empírico. Se inicia con el posicionamiento del investigador, la metodología, las técnicas a utilizar y el proceso de aterrizaje en el campo. Posteriormente se realiza el tratamiento empírico, comenzando a partir de los datos obtenidos con la técnica SAATY donde adquiere relevancia la participación del grupo de expertos delimitando con ellos las variables, categorías e indicadores; posteriormente se muestran los resultados de las técnicas cuantitativas, en primer lugar con el análisis y presentación de los datos de las fuentes secundarias, y en segundo, con la generación de los perfiles sociales construidos a partir de los datos de las fuentes primarias y utilizando como instrumento el programa estadístico SPSS. Se finaliza con los resultados de las técnicas cualitativas que se desprenden de las entrevistas focales a profesionales, centradas fundamentalmente en el análisis del escenario social y judicial, y complementándolo con la subjetividad y narrativa aportada por los relatos de jóvenes que fueron adolescentes en conflicto con la ley. La tercera parte incluye los capítulos decimosegundo y decimotercero destinados a las conclusiones. El primero de ellos es la discusión sobre los resultados triangulados desde las diferentes técnicas, comparándolos con otras investigaciones y aportes teóricos para hallar semejanzas, diferencias y avances en el conocimiento del fenómeno. En este sentido se realiza el contraste de las hipótesis. Y el segundo, aventura implicaciones políticas y metodológicas para la práctica profesional. Reflexiona sobre el modelo de justicia juvenil y propone el anclaje en lo local, en el territorio y en la proximidad para intervenir con garantías de éxito en las trayectorias, en los escenarios y en los itinerarios. Sólo así se garantizan políticas preventivas no selectivas, escenarios socioeducativos e itinerarios integradores. Finalmente se hallan las fuentes bibliográficas y los anexos que recogen todos los datos obtenidos y su tratamiento desde las diferentes técnicas. / This work starts from the premise to identify vulnerabilities and social exclusion processes of adolescents in conflict with the law, to establish the relationship between vulnerability and criminal trajectories generation just as its treatment at the scene and its projection to the itinerary .To facilitate understanding of the argument we divide it into three parts: The first part extends from the first chapter to the fifth one, and specifies the theoretical foundations of the study. It begins explaining the paradigm of vulnerability and social exclusion as background of the object under investigation, it continues with a foray into sociological theories of juvenile delinquency to determine positions on its social origin, highlight its complexity and the difficulties of conceptualization. Also are analyzed the treatment models because opting for one and not for another is a criminal policy option related to criminal juvenile justice model and to the concept of crime and delinquency in a society. The second part covers the sixth to the eleventh chapter, includes the methodological foundations and empirical analysis. It starts with the technique Saaty where is very important the participation of the expert group to define the variables, categories and indicators; later are showed the results of quantitative techniques with the analysis of secondary sources, and with the generation of social profiles constructed from the data of primary sources. It ends with the results of qualitative techniques from focal interviews with professionals and supplemented with the subjectivity provided by the stories of young people. The third part includes the twelfth and thirteenth chapters devoted to the conclusions. The first of them contains the discussion on the triangulated results from the different techniques, comparing them with other research and theoretical contributions to find similarities, differences and advances in the understanding of the phenomenon. Finally the last chapter ventures methodological and political implications for professional practice. It reflects on the model of juvenile justice and proposes anchoring to the local issues, to the territory and proximity to intervene in the trajectories, scenarios and routes.

Background: Anthracyclines, in particular Doxorubicin (DOX), are highly effective chemotherapeutic agents in the breast cancer setting, which are limited by their cardiotoxic side effects. Recently, the introduction of Trastuzumab (TRZ), a novel monoclonal antibody against the HER2 receptor, in the breast cancer setting compounds the issue of DOX mediated cardiac dysfunction. Amongst the potential mechanisms for the deleterious effects of this drug-induced cardiomyopathy, the relationship between nitric oxide synthase 3 (NOS3) and oxidative stress has gained recent attention. Objective: To determine the role of NOS3 in a clinically relevant female murine model of DOX+TRZ induced heart failure. Methods: A total of 120 C57Bl/6 female mice [60 wild type (WT) and 60 NOS3 knockout (NOS3-/-)] were treated with either 0.9% saline, DOX (20 mg/kg), TRZ (10 mg/kg), or DOX+TRZ. Serial echocardiography was performed daily for a total of 10 days, after which the mice were euthanized for histological and biochemical analyses. Results: As compared to WT, NOS3-/- mice demonstrated increased cardiotoxicity following treatment with DOX. This effect was potentiated with DOX+TRZ combination therapy. In WT female mice receiving DOX+TRZ, left ventricular ejection fraction (LVEF) decreased from 75±3% at baseline to 46±2% at day 10 (p<0.05). In the NOS3-/- group, LVEF decreased from 72±3% at baseline to 35±2% at day 10 (p<0.05). LVEF was significantly lower in NOS3-/- mice than WT at day 10 in those receiving DOX+TRZ (p<0.05). As compared to WT, NOS3-/- mice also demonstrated increased mortality following treatment with DOX+TRZ, corroborating the echocardiographic findings. Histological analysis using light and electron microscopy demonstrated increased loss of cell integrity including myofibrillar degradation, cytoplasmic vacuolization, and enlargement of the smooth endoplasmic reticulum in both the WT and NOS3-/- mice treated with DOX+TRZ. There was no significant difference, however, in the degree of cardiac remodeling between the WT and NOS3-/- groups. There was an increasing trend in the degree of cardiac apoptosis in both WT and NOS3-/- mice treated with DOX+TRZ therapy. Conclusion: Congenital absence of NOS3 potentiates the cardiotoxic effects of DOX+TRZ in an acute female murine model of chemotherapy-induced cardiomyopathy.

Esta tesis es una investigación cualitativa cuyo objetivo es explorar y comprender los cuidados ofrecidos a los moribundos desde la perspectiva enfermera. Se siguen los procedimientos de la Teoría Fundamentada y por ello, la pregunta de investigación: ¿Cómo viven las enfermeras de ámbitos no especializados (con) los cuidados cercanos a la muerte?, se abordará desde el análisis de la voz de las profesionales. Palabras que entrañan significados y valores determinando su actitud y participación en el cuidado. Los ejes emergentes: morir de una persona, cuidados al moribundo y la familia y repercusiones del cuidar, muestran la importancia de estos procesos. Importancia plasmada en la cocreacíon de un sistema que los acoge y donde la buena muerte es el objetivo prioritario. Espacio donde afloran elementos en sintonía con la teoría del Ser Humano en Devenir de Parse; desde donde se analizarán con el fin de aportar herramientas útiles para los cuidados al final de la vida. / This thesis is a qualitative research which aim is to explore and understand the care given to the moribund patients from the nursing perspective. Procedures of grounded theory are followed and therefore the research question (how nurses of non-specialized area live (with) care near the death?) will be addressed from the analysis of the meanings and values of the professional word that determine their attitude and participation in care. The focus of analysis: the death of a person, care for the moribund patient and the family, and the impact of caring for the professional, show the importance of these processes and the positioning of the nurses at the phenomenon of study. It is co created a system where the search for a good death is the priority. A space where elements emerge in harmony with the Human Becoming theory of Parse which will be analyzed in order to provide useful tools for care at the end of life.