Impact of genetic SLC28 transporter and ITPA variants on ribavirin serum level, hemoglobin drop and therapeutic response in patients with HCV infection

In the last decade, pegylated interferon-α (PegIFN-α) plus ribavirin (RBV) was the standard treatment of chronic hepatitis C for genotype 1, and it remains the standard for genotypes 2 and 3. Recent studies reported associations between RBV-induced anemia and genetic polymorphisms of concentrative nucleoside transporters such as CNT3 (encoded by SLC28A3) and inosine triphosphatase (encoded by ITPA). We aimed at studying genetic determinants of RBV kinetics, efficacy and treatment-associated anemia.

Clasificación de madera estructural de gran escuadría de Pinus sylvestris l. mediante métodos no destructivos

Esta Tesis Doctoral aborda el estudio de algunas técnicas no destructivas para la clasificación de madera de pino silvestre (Pinus sylvestris L.) de procedencia española y de gruesa escuadría para uso estructural. Para la estimación del módulo de elasticidad y de la resistencia se han aplicado técnicas basadas en la propagación de una onda a través de la madera: onda de ultrasonidos (Sylvatest) o de impacto (Microsecond Timer) en dirección longitudinal, o vibración en dirección longitudinal y transversal (PLG). Para la estimación de la densidad se han utilizado métodos puntuales basados en el penetrómetro (Pilodyn) y en la resistencia al arranque de un tornillo. Las variables obtenidas han sido relacionadas con los resultados de la clasificación visual y con las propiedades de la madera determinadas mediante ensayo mecánico. Además, se ha estudiado la influencia de la humedad de la madera en la velocidad de propagación de la onda para definir factores de corrección a los equipos comerciales utilizados en esta Tesis Doctoral. La muestra de estudio está formada por 244 piezas procedentes de El Espinar, Segovia, con dimensiones nominales 150 x 200 x 4000 mm (218 piezas) y 100 x 150 x 3000 mm (26 piezas). De todas las piezas se tomaron datos de dimensiones, contenido de humedad y clasificación visual según la norma UNE 56544. En las primeras 218 vigas se aplicaron las técnicas de ultrasonidos, onda de impacto y vibraciones, se determinó la densidad de cada pieza completa y se ensayaron según la norma UNE-EN 408 para obtener el módulo de elasticidad global (en todos los casos) y local (en un porcentaje), así como de la tensión de rotura. Se extrajeron tres rebanadas para los ensayos puntuales y para el cálculo de la densidad. En las otras 26 piezas se repitieron los ensayos (transmisión de onda, vibración y clasificación visual) durante el proceso de secado natural, desde que la madera se encontraba húmeda (en torno al 40 %) hasta la humedad de equilibrio higroscópico (en torno al 9%). Respecto a la clasificación visual no se han observado diferencias significativas entre la calidad MEG o las rechazadas. Se han estudiado las consecuencias del secado (principalmente las deformaciones) y no se ha encontrado justificación para que estos defectos penalicen la clasificación. Para la densidad, el mayor R2 obtenido ha sido de un 47% a partir del uso combinado de los dos equipos puntuales (penetrómetro y arranque de tornillo). Para el módulo de elasticidad y la tensión de rotura, la mejor relación se ha obtenido a partir de la técnica de vibración longitudinal, con unos coeficientes de 79% y un 52% respectivamente. Se ha estimado que el aumento de un punto porcentual en el contenido de humedad de la madera produce una pérdida de velocidad de onda del 0,58% para Sylvatest y Microsecond Timer, y del 0,71% para PLG. Estos valores son generalizables para un rango de humedades entre 9 y 25 %. Abstract This Doctoral Thesis approach the study of some non-destructive techniques as a classification method for structural use of Scots pine wood of Spanish origin with large cross section. To estimate the modulus of elasticity and strength have been used techniques based on the propagation of a wave through the timber: ultrasonic wave (Sylvatest) or stress wave (Microsecond Timer) in longitudinal direction, or vibration in longitudinal and transversal direction (PLG). Local probing methods have been applied to estimate the density, based on penetrometer (Pilodyn) and the screw withdrawal resistance meter. The different variables obtained were compared with the results of the visual grading and the values of the properties of the wood determined by the standardized test of the pieces. Furthermore, the influence of the moisture content of the wood on the velocity of propagation of the waves through the timber has been analyzed in order to establish a correction factor for the commercial devices used in this Doctoral Thesis. The sample tested consists of 244 pieces from El Espinar, Segovia, with nominal dimensions 150 x 200 x 4000 mm (218 pieces) and 100 x 150 x 3000 mm (26 pieces). Data collection about dimensions, moisture content and visual grading according to the UNE 56544 standard were carried out on all the pieces. The first 218 pieces were tested by non destructive techniques based on ultrasonic wave, stress wave and vibration, the density was measured on each piece and bending test according to the UNE-EN 408 standard was carried out for calculating the global modulus of elasticity (all the pieces) and the local one (only a representative group), as well as the bending strength. Three slices were removed for implementing the local probing and to calculate the density. In the other 26 pieces the tests (wave transmission, vibration and visual grading) were repeated during the natural drying process, from wet timber (around 40 % moisture content) up to the equilibrium moisture content (around 9%). Regarding the visual grading no significant differences were observed between MEG or rejected pieces. The effects of drying (deformations) have been studied, and justification for the specification hasn't been found. To estimate the density, the greater R2 obtained was 47% by using both penetrometer and screw withdrawal. For the modulus of elasticity and bending strength, the best relationship has been found with the longitudinal vibration, with coefficients of 79% and 52% respectively. It has been estimated that an increase of a point of the moisture content of the wood produces a decrease on the velocity obtained from ultrasonic or stress wave of 0,58%, and 0,71 % for the one obtained from vibration. Those values can be generalized for a range of moisture content from 9 to 25 %.

Conserved biological function between Pax-2 and Pax-5 in midbrain and cerebellum development: Evidence from targeted mutations

The development of two major subdivisions of the vertebrate nervous system, the midbrain and the cerebellum, is controlled by signals emanating from a constriction in the neural primordium called the midbrain/hindbrain organizer (Joyner, A. L. (1996) Trends Genet. 12, 15–201). The closely related transcription factors Pax-2 and Pax-5 exhibit an overlapping expression pattern very early in the developing midbrain/hindbrain junction. Experiments carried out in fish (Krauss, S., Maden, M., Holder, N. & Wilson, S. W. (1992) Nature (London) 360, 87–89) with neutralizing antibodies against Pax-b, the orthologue of Pax-2 in mouse, placed this gene family in an regulatory cascade necessary for the development of the midbrain and the cerebellum. The targeted mutation of Pax-5 has been reported to have only slight effects in the development of structures derived from the isthmic constriction, whereas the Pax-2 null mutant mice show a background-dependent phenotype with varying penetrance. To test a possible redundant function between Pax-2 and Pax-5 we analyzed the brain phenotypes of mice expressing different dosages of both genes. Our results demonstrate a conserved biological function of both proteins in midbrain/hindbrain regionalization. Additionally, we show that one allele of Pax-2, but not Pax-5, is necessary and sufficient for midbrain and cerebellum development in C57BL/6 mice.

Properties of seawater from a Sea-Bird TSG temperature and conductivity sensor mounted on the continuous surface water sampling system during campaign TARA_20100624Z of the Tara Oceans expedition 2009-2013

The Tara Oceans Expedition (2009-2013) sampled the world oceans on board a 36 m long schooner, collecting environmental data and organisms from viruses to planktonic metazoans for later analyses using modern sequencing and state-of-the-art imaging technologies. Tara Oceans Data are particularly suited to study the genetic, morphological and functional diversity of plankton. The present data publication contains measurements from the Continuous Surface Sampling System [CSSS] made during one campaign of the Tara Oceans Expedition. Water was pumped at the front of the vessel from ~2m depth, then de-bubbled and circulated to a Sea-Bird TSG temperature and conductivity sensor. System maintenance (instrument cleaning, flushing) was done approximately once a week and in port between successive legs. All data were stamped with a GPS.

Étude du mécanisme de décalage de phase de lecture en-1 du virus de l'immunodéficience humaine de type 1 et de son importance dans la réplication du virus

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Étude du mécanisme de décalage de phase de lecture en-1 du virus de l'immunodéficience humaine de type 1 et de son importance dans la réplication du virus

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

A Rare Presentation of Leptospirosis

Leptospirosis has a wide spectrum of clinical manifestations. Acute renal failure, an important complication, generally involves interstitial and tubular damage. We describe the case of a 42-year-old man who was admitted with fever, back pain and periorbital oedema. He had hypertension, thrombocytopenia, acute renal failure, hypoalbuminaemia, hypertriglyceridaemia and proteinuria >4.00 g/l. The renal biopsy showed mesangioproliferative glomerulonephritis. Due to the epidemiological context and clinical picture, ceftriaxone was started with rapid clinical improvement. Blood PCR for leptospira came back positive. The presentation of leptospirosis as nephrotic syndrome is rare and this diagnosis should be considered before performing a renal biopsy.

A Cavalaria Portuguesa e as Missões de Paz : Reflexos da mudança da Arte Militar

O Exército Português tem projetado contingentes para participar em Missões de Paz sob e égide das principais Organizações Internacionais. Estas missões, pela sua complexidade exigiram das instituições militares a capacidade de atuar em conflitos em que as entidades desestabilizadoras se encontram no seio da população. O presente trabalho está subordinado ao tema: “A Cavalaria Portuguesa e as Missões de Paz – Reflexos da Mudança da Arte Militar” e o objectivo desta investigação é compreender as alterações efetuadas nas Unidades de Cavalaria projetadas em Operações de Apoio à Paz no Teatro de Operações do Kosovo. A metodologia utilizada para a realização do mesmo foi feita através do método indutivo, em que foi feito um estudo de caso baseado em Unidades de Cavalaria projetadas em Operações de Apoio à Paz no Teatro de Operações do Kosovo, com o objetivo de formular ideias e princípios a serem utilizados no Exército Português quer no mesmo teatro, quer em outros. A recolha de informação surgiu da análise documental e de algumas entrevistas feitas a militares que participaram em missões no Teatro de Operações do Kosovo. Os resultados espelharam que as mais notáveis alterações a nível orgânico, de instrução e treino e de emprego de viaturas blindadas no teatro refletiram-se sobretudo pela integração na Reserva Tática do Kosovo Force e consequentemente pela gradual pacificação do conflito.