Effects of supplemental osteopontin on intestinal development and serum antibody responses to rotavirus vaccination in piglets

Milk contains numerous bioactive substances including immunoglobulins, cytokines, growth factors and components that exert antibiotic and prebiotic activity (Field, 2005). Little is known about the biological effects of individual milk bioactives, despite the fact that natural milk improves intestinal development and immune system functions in neonates (Donovan et al., 1994; Field, 2005) relative to milk formula. Characterization of the biological effects of such components is important for optimal production of infant milk formulas to be used when mother’s milk is not available. Milk components with preliminary evidence of positive effects on the intestinal growth and mucosal immunity include osteopontin (OPN). Osteopontin is a phosphorylated acidic glycoprotein expressed by a number of different immune and non-immune cells and tissues (Sodek et al., 2000). It is also present in body fluids including blood, bile and milk (Sodek et al., 2000). Osteopontin is a multifunctional protein that is implicated in a wide number of biological processes including cell survival, bone remodeling, and immune modulatory functions (Sodek et al., 2000). Furthermore, Schack and colleagues (2009) demonstrated that the concentration of OPN in human milk is considerably higher than in bovine milk and infant formulas. Taken together, it is likely that OPN plays a role in the early development of gastrointestinal tract and mucosal immune responses in infants. Since the neonatal pig shares anatomical, physiological, immunological, and metabolic similarities with the human infants (Moughan, et al., 1992), they were selected as the animal model in our studies. Our first aim was to investigate the effects of OPN on piglet intestinal development. Newborn, colostrum-deprived piglets (n=27) were randomized to receive three treatments: formula with bovine OPN (OPN; 140 mg/L); formula alone (FF); or sow reared (SR) for 21 days. Body weight, intestinal weight and length, mucosal protein and DNA content, disaccharidase activity, villus morphology, and crypt cell proliferation were measured. Statistical significance was assigned at P<0.05. No significant effects of OPN were observed for body weight, intestinal weight and length. Mucosal protein content of SR piglets was lower than FF and OPN piglets in the duodenum, but higher than FF and OPN piglets in the ileum. No significant effects of diet in mucosal DNA content were detected for the three regions of the small intestine. Lactase and sucrase activities of SR piglets were higher than the two formula-fed groups in the duodenum, lower in the ileum. No significant effects of diet on lactase and sucrase activities were noted between two formula-fed groups in the duodenum and ileum. Jejunal lactase activity of FF piglets was higher than SR piglets, whereas no significant effect of diet was observed in jejunal sucrase activity among the three groups. Duodenal and ileal villus height and villus area of SR piglets were lower than two formula-fed groups, while OPN piglets did not differ from FF piglets. There was a significant effect of diet (P<0.0001) on jejunal crypt cell proliferation, with proliferation in OPN piglets being intermediate between that of FF and SR. In summary, supplemental OPN increased jejunal crypt cell proliferation, independent of evident morphological growth, and had a minor impact on disaccharidase activity in the small intestine of neonatal piglets. Rotavirus (RV) is the most common viral cause of severe gastroenteritis in infants and young children worldwide (Parashar et al., 2006). Maeno et al. (2009) reported that OPN knockout (OPN-KO) suckling mice were more susceptible to RV infection compared to wild-type (WT) suckling mice. To detect the role of OPN in intestinal immune responses of neonates, the goal of the second study was to evaluate whether supplemental OPN influenced the serum antibody responses to RV vaccination in neonatal piglets. Newborn, colostrum-deprived piglets were randomized into two dietary groups: formula with bovine OPN (OPN; 140 mg/L) and formula alone (FF) for 35 days. On d7, piglets in each dietary group were further randomized to receive rotavirus (RV) vaccination (Rotarix®) (FF+RV and OPN+RV) or remained non-vaccinated (FF+NV and OPN+NV). Booster vaccination was provided on d14. Blood samples were collected on d7, 14, 21, 28 and 35. RV-specific serum immunoglobulin (Ig) G, IgA, IgM and total serum IgG, IgA, IgM were measured by ELISA. Statistical significance was assigned at P<0.05, with trends reported as P<0.10. Body weight gain was unaffected by diet and/or vaccination. No significant effect of oral OPN supplementation was observed for RV-specific antibody responses and total Igs levels. After the combination of dietary groups, RV piglets had significantly higher RV-specific IgM concentrations compared to NV piglets. Although there were higher means of RV-specific IgG and RV-specific IgA concentrations in RV group than their counterparts in NV group, the difference did not reach statistical significance. RV-specific IgM reached a peak at d7 post booster vaccination (PBV), whereas the RV-specific IgG and IgA peaked later at PBV 14 or 21. Total Igs were unaffected by RV vaccination but were significantly increased over time, following similar pattern as RV-specific Igs. In summary, neonatal piglets generated weak antibody responses to RV vaccination. Supplemental OPN did not enhance RV-specific serum antibody responses and total serum Igs levels in neonatal piglets with or without RV vaccination. In conclusion, we observed normal developmental changes in the small intestine and serum Igs levels in neonatal piglets over time. Oral OPN supplementation showed minimal impacts on intestinal development and no effect on serum Igs levels. The role of supplemental OPN on the growth and development of infants is still inconclusive. Future studies should measure other physiological and immunological parameters by using different models of vaccination or infection.

Haemocompatibility of iron oxide nanoparticles synthesized for theranostic applications: a high-sensitivity microfluidic tool

The poor heating efficiency of the most reported magnetic nanoparticles (MNPs), allied to the lack of comprehensive biocompatibility and haemodynamic studies, hampers the spread of multifunctional nanoparticles as the next generation of therapeutic bio-agents in medicine. The present work reports the synthesis and characterization, with special focus on biological/toxicological compatibility, of superparamagnetic nanoparticles with diameter around 18 nm, suitable for theranostic applications (i.e. simultaneous diagnosis and therapy of cancer). Envisioning more insights into the complex nanoparticle-red blood cells (RBCs) membrane interaction, the deformability of the human RBCs in contact with magnetic nanoparticles (MNPs) was assessed for the first time with a microfluidic extensional approach, and used as an indicator of haematological disorders in comparison with a conventional haematological test, i.e. the haemolysis analysis. Microfluidic results highlight the potential of this microfluidic tool over traditional haemolysis analysis, by detecting small increments in the rigidity of the blood cells, when traditional haemotoxicology analysis showed no significant alteration (haemolysis rates lower than 2 %). The detected rigidity has been predicted to be due to the wrapping of small MNPs by the bilayer membrane of the RBCs, which is directly related to MNPs size, shape and composition. The proposed microfluidic tool adds a new dimension into the field of nanomedicine, allowing to be applied as a highsensitivity technique capable of bringing a better understanding of the biological impact of nanoparticles developed for clinical applications.

Anteproyecto arquitectónico diseño de un conjunto de residencias universitarias

El presente trabajo de grado previo a la obtención del título de Arquitecto, presenta una propuesta de diseño de un conjunto de residencias universitarias, un servicio y equipamiento que la ciudad evidencia que ya lo necesita. El anteproyecto no sólo está dirigido a la edificación de vivienda para estudiantes sino como un espacio apto para actividades académicas, espacios destina¬dos a dar un lugar para descansar y a su vez para estudiar y prepararse para la próxima vida profesional que le tocará vivir. La edificación está resuelta en base a módulos habitacionales para uno, dos, tres o cuatro usuarios, y otro destinado a un usuario con capacidades diferentes. Los espacios son multifuncionales y versátiles, ayudando así a las diversas tareas que podrían desarrollar los usuarios en las distintas carreras profesionales. Además el proyecto prevé la ubicación de espacios y servicios complementa¬rios indispensables para facilidad de los usuarios: cajeros, salas de estudio, cafetería, gimnasio, etc. Finalmente el proyecto se localizó de tal manera que quedará a distancias equitativas de las princi¬pales universidades de Cuenca.

Estudo do papel da proteína multifuncional APE1/Ref-1 sobre a resposta inflamatória na meningite bacteriana

Despite advances in antibiotic therapy, bacterial meningitis (BM) remains with high mortality and morbidity rates in worldwide. One important mechanism associated to sequels during disease is the intense inflammatory response which promotes an oxidative burst and release of reactive oxygen species, consequently leading to cell death. Activation of DNA repair enzymes during oxidative stress has been demonstrated in several neurological disorders. APE1/Ref-1 is a multifunctional protein involved in DNA repair and plays a redox function on transcription factors such as NFkB and AP-1.The aim of this study was assess the role of APE1/Ref-1 on inflammatory response and the possibility of its modulation to reduce the sequels of the disease. Firstly it was performed an assay to measure cytokine in cerebrospinal fluid of patients with BM due to Streptococcus pneumoniae and Neisseriae meningitides. Further, a cellular model of inflammation was used to observe the effect of the inhibition of the endonuclease and redox activity of APE1/Ref-1 on cytokine levels. Additionally, APE1/Ref-1 expression in cortex and hippocampus of rat with MB after vitamin B6 treatment was evaluated. Altogether, results showed a similar profile of cytokines in the cerebrospinal fluid of patients from both pathogens, although IFNy showed higher expression in patients with BM caused by S. pneumoniae. On the other hand, inhibitors of APE1/Ref-1 reduced cytokine levels, mainly TNF-α. Reduction of oxidative stress markers was also observed after introduction of inhibitors in the LPS-stimulated cell. In the animal model, BM increased the expression of the protein APE1/Ref-1, while vitamin B6 promoted reduction. Thereby, this data rise important factors to be considered in pathogenesis of BM, e.g., IFNy can be used as prognostic factor during corticosteroid therapy, APE1/Ref-1 can be an important target to modulate the level of inflammation and VIII oxidative stress, and vitamin B6 seems modulates several proteins related to cell death. So, this study highlights a new understanding on the role of APE1/Ref-1 on the inflammation and the oxidative stress during inflammation condition

Proton conductivity and luminiscence properties of lanthanide aminotriphosphonates

Metal phosphonates are multifunctional solids with tunable properties, such as internal H-bond networks, and high chemical and thermal stability [1]. In the present work, we describe the synthesis, structural characterization, luminescent properties and proton conduction performance of a new family of isostructural cationic compounds with general formula [Ln(H4NMP)(H2O)2]Cl·2H2O [Ln = La3+, Pr3+, Sm3+, Gd3+, Tb3+, Dy3+, Ho3+, H6NMP = nitrilotris(methylphosphonic acid)]. These solids are formed by positively charge layers, which consist of isolated LnO8 polyhedra and bridge chelating NMP2- ligands, held apart by chloride ions and water molecules. This arrangement result in extended interlayer hydrogen networks with possible proton transfer pathways. The proton conductivity of Gd3+ sample, selected as prototype of the series, was measured. In the range between range 25º and 80 ºC, the conductivity increase with the temperature up to a maximum value of 3.10-4 S·cm-1, at relative humidity of 95 %. The activation energy obtained from the Arrhenius plot (Figure 1) is in the range corresponding to a Grotthuss transfer mechanism.

Aqueous solubilities of five N-(diethylaminothiocarbonyl)benzimido derivatives at T = 298.15 K

N-(diethylaminothiocarbonyl)benzimido derivatives are polar multifunctional substances. A set of these compounds was synthesised by successive substitution on the enamine side, resulting in similar substances with different polarities, providing a set of model compounds with respect to the study of substituent effects on physico-chemical properties. Experimental aqueous solubility data, at T = 298.15 K, of N-(diethylaminothiocarbonyl)benzamidine, PhCNH2NCSNEt2 (1),N-(diethylaminothiocarbonyl)-N'-phenylbenzamidine, PhCNHPhNCSNEt2 (2), N-(diethylaminothiocarbonyl)-N'-monoethylbenzamidine, PhCNHEtNCSNEt2 (3), N-(diethylaminothiocarbonyl)-N',N'-diethylbenzamidine, PhCNEt2NCSNEt2 (4), and N-(diethylaminothiocarbonyl)benzimido ethylester, PhCOEtNCSNEt2 (5) were measured at T = 298.15 K. The obtained data are supplemented by COSMO-RS aqueous solubility predictions as well as other environmentally important partition coefficients. This information is shown in a two-dimensional chemical space diagram, providing indications about the compartment into which the bulk of the compounds is likely to concentrate. The expected quality of COSMO-RS predictions for this type of screening exercise is illustrated on a set of pesticides with established thermophysical property data.

Integración de dispositivos electrónicos inteligentes en Smart Grid

El sector eléctrico está experimentando cambios importantes tanto a nivel de gestión como a nivel de mercado. Una de las claves que están acelerando este cambio es la penetración cada vez mayor de los Sistemas de Generación Distribuida (DER), que están dando un mayor protagonismo al usuario a la hora de plantear la gestión del sistema eléctrico. La complejidad del escenario que se prevé en un futuro próximo, exige que los equipos de la red tenga la capacidad de interactuar en un sistema mucho más dinámico que en el presente, donde la interfaz de conexión deberá estar dotada de la inteligencia necesaria y capacidad de comunicación para que todo el sistema pueda ser gestionado en su conjunto de manera eficaz. En la actualidad estamos siendo testigos de la transición desde el modelo de sistema eléctrico tradicional hacia un nuevo sistema, activo e inteligente, que se conoce como Smart Grid. En esta tesis se presenta el estudio de un Dispositivo Electrónico Inteligente (IED) orientado a aportar soluciones para las necesidades que la evolución del sistema eléctrico requiere, que sea capaz de integrase en el equipamiento actual y futuro de la red, aportando funcionalidades y por tanto valor añadido a estos sistemas. Para situar las necesidades de estos IED se ha llevado a cabo un amplio estudio de antecedentes, comenzando por analizar la evolución histórica de estos sistemas, las características de la interconexión eléctrica que han de controlar, las diversas funciones y soluciones que deben aportar, llegando finalmente a una revisión del estado del arte actual. Dentro de estos antecedentes, también se lleva a cabo una revisión normativa, a nivel internacional y nacional, necesaria para situarse desde el punto de vista de los distintos requerimientos que deben cumplir estos dispositivos. A continuación se exponen las especificaciones y consideraciones necesarias para su diseño, así como su arquitectura multifuncional. En este punto del trabajo, se proponen algunos enfoques originales en el diseño, relacionados con la arquitectura del IED y cómo deben sincronizarse los datos, dependiendo de la naturaleza de los eventos y las distintas funcionalidades. El desarrollo del sistema continua con el diseño de los diferentes subsistemas que lo componen, donde se presentan algunos algoritmos novedosos, como el enfoque del sistema anti-islanding con detección múltiple ponderada. Diseñada la arquitectura y funciones del IED, se expone el desarrollo de un prototipo basado en una plataforma hardware. Para ello se analizan los requisitos necesarios que debe tener, y se justifica la elección de una plataforma embebida de altas prestaciones que incluye un procesador y una FPGA. El prototipo desarrollado se somete a un protocolo de pruebas de Clase A, según las normas IEC 61000-4-30 e IEC 62586-2, para comprobar la monitorización de parámetros. También se presentan diversas pruebas en las que se han estimado los retardos implicados en los algoritmos relacionados con las protecciones. Finalmente se comenta un escenario de prueba real, dentro del contexto de un proyecto del Plan Nacional de Investigación, donde este prototipo ha sido integrado en un inversor dotándole de la inteligencia necesaria para un futuro contexto Smart Grid.

Diamond Surface Modification to Enhance Interfacial Thermal Conductivity in Al/Diamond Composites

Diamond/metal composites are very attractive materials for electronics because their excellent thermal properties make them suitable for use as heat sink elements in multifunctional electronic packaging systems. To enlarge the potential applications of these composites, current efforts are mainly focused on investigating different ways to improve the contact between metal and diamond. In the present work, a theoretical study has been carried out to determine the differences between the interfacial thermal conductance of aluminum/diamond and aluminum/graphite interfaces. Additionally, diamond particles were surface modified with oxygen to observe how it affects the quality of the diamond surface. The characterization of the surface of diamonds has been performed using different surface analysis techniques, especially x-ray photoelectron spectroscopy and temperature-programmed desorption.

Construir no construído

Dissertação de Mestrado para obtenção do grau de Mestre em Arquitectura, apresentada na Universidade de Lisboa - Faculdade de Arquitectura.

O interface do Campo Grande

Dissertação para obtenção do grau de Mestre em Arquitectura com Especialização em Urbanismo, apresentada na Universidade de Lisboa - Faculdade de Arquitectura.

Parques de campismo. Uma proposta de projeto para a Mata Nacional do Urso

Dissertação de Mestrado, Arquitetura Paisagista, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2016

Flexibilidade da casa

Dissertação para obtenção do grau de Mestre em Arquitectura, apresentada na Universidade de Lisboa - Faculdade de Arquitectura.

O redesenho urbano como gerador de espaços colectivos

Dissertação para obtenção do grau de Mestre em Arquitectura, apresentada na Universidade de Lisboa - Faculdade de Arquitectura.

A viabilidade económica da gestão sustentável do montado de sobreiro. Caso de estudo - Aldeia das Amoreiras

Dissertação de Mestrado, Economia do Turismo e Desenvolvimento Regional, Faculdade de Economia, Universidade do Algarve, 2016

Revitalização da cidade construída

Dissertação para obtenção do grau de Mestre em Arquitetura de Interiores, apresentada na Universidade de Lisboa - Faculdade de Arquitetura.