Pharmacogenetics of MicroRNAs and MicroRNAs Biogenesis Machinery in Pediatric Acute Lymphoblastic Leukemia

Despite the clinical success of acute lymphoblastic leukemia (ALL) therapy, toxicity is frequent. Therefore, it would be useful to identify predictors of adverse effects. In the last years, several studies have investigated the relationship between genetic variation and treatment-related toxicity. However, most of these studies are focused in coding regions. Nowadays, it is known that regions that do not codify proteins, such as microRNAs (miRNAs), may have an important regulatory function. MiRNAs can regulate the expression of genes affecting drug response. In fact, the expression of some of those miRNAs has been associated with drug response. Genetic variations affecting miRNAs can modify their function, which may lead to drug sensitivity. The aim of this study was to detect new toxicity markers in pediatric B-ALL, studying miRNA-related polymorphisms, which can affect miRNA levels and function. We analyzed 118 SNPs in pre-miRNAs and miRNA processing genes in association with toxicity in 152 pediatric B-ALL patients all treated with the same protocol (LAL/SHOP). Among the results found, we detected for the first time an association between rs639174 in DROSHA and vomits that remained statistically significant after FDR correction. DROSHA had been associated with alterations in miRNAs expression, which could affect genes involved in drug transport. This suggests that miRNA-related SNPs could be a useful tool for toxicity prediction in pediatric B-ALL.

Structured discriminative models for noise robust continuous speech recognition

Recently there has been interest in structured discriminative models for speech recognition. In these models sentence posteriors are directly modelled, given a set of features extracted from the observation sequence, and hypothesised word sequence. In previous work these discriminative models have been combined with features derived from generative models for noise-robust speech recognition for continuous digits. This paper extends this work to medium to large vocabulary tasks. The form of the score-space extracted using the generative models, and parameter tying of the discriminative model, are both discussed. Update formulae for both conditional maximum likelihood and minimum Bayes' risk training are described. Experimental results are presented on small and medium to large vocabulary noise-corrupted speech recognition tasks: AURORA 2 and 4. © 2011 IEEE.

Model-based approaches to handling additive noise in reverberant environments

Model-based approaches to handle additive and convolutional noise have been extensively investigated and used. However, the application of these schemes to handling reverberant noise has received less attention. This paper examines the extension of two standard additive/convolutional noise approaches to handling reverberant noise. The first is an extension of vector Taylor series (VTS) compensation, reverberant VTS, where a mismatch function including reverberant noise is used. The second scheme modifies constrained MLLR to allow a wide-span of frames to be taken into account and projected into the required dimensionality. To allow additive noise to be handled, both these schemes are combined with standard VTS. The approaches are evaluated and compared on two tasks, MC-WSJ-AV, and a reverberant simulated version of AURORA-4. © 2011 IEEE.

Derivative Kernels for Noise Robust ASR

Recently there has been interest in combined gen- erative/discriminative classifiers. In these classifiers features for the discriminative models are derived from generative kernels. One advantage of using generative kernels is that systematic approaches exist how to introduce complex dependencies beyond conditional independence assumptions. Furthermore, by using generative kernels model-based compensation/adaptation tech- niques can be applied to make discriminative models robust to noise/speaker conditions. This paper extends previous work with combined generative/discriminative classifiers in several directions. First, it introduces derivative kernels based on context- dependent generative models. Second, it describes how derivative kernels can be incorporated in continuous discriminative models. Third, it addresses the issues associated with large number of classes and parameters when context-dependent models and high- dimensional features of derivative kernels are used. The approach is evaluated on two noise-corrupted tasks: small vocabulary AURORA 2 and medium-to-large vocabulary AURORA 4 task.

Derivative kernels for noise robust ASR

Recently there has been interest in combining generative and discriminative classifiers. In these classifiers features for the discriminative models are derived from the generative kernels. One advantage of using generative kernels is that systematic approaches exist to introduce complex dependencies into the feature-space. Furthermore, as the features are based on generative models standard model-based compensation and adaptation techniques can be applied to make discriminative models robust to noise and speaker conditions. This paper extends previous work in this framework in several directions. First, it introduces derivative kernels based on context-dependent generative models. Second, it describes how derivative kernels can be incorporated in structured discriminative models. Third, it addresses the issues associated with large number of classes and parameters when context-dependent models and high-dimensional feature-spaces of derivative kernels are used. The approach is evaluated on two noise-corrupted tasks: small vocabulary AURORA 2 and medium-to-large vocabulary AURORA 4 task. © 2011 IEEE.

Extending noise robust structured support vector machines to larger vocabulary tasks

This paper describes a structured SVM framework suitable for noise-robust medium/large vocabulary speech recognition. Several theoretical and practical extensions to previous work on small vocabulary tasks are detailed. The joint feature space based on word models is extended to allow context-dependent triphone models to be used. By interpreting the structured SVM as a large margin log-linear model, illustrates that there is an implicit assumption that the prior of the discriminative parameter is a zero mean Gaussian. However, depending on the definition of likelihood feature space, a non-zero prior may be more appropriate. A general Gaussian prior is incorporated into the large margin training criterion in a form that allows the cutting plan algorithm to be directly applied. To further speed up the training process, 1-slack algorithm, caching competing hypothesis and parallelization strategies are also proposed. The performance of structured SVMs is evaluated on noise corrupted medium vocabulary speech recognition task: AURORA 4. © 2011 IEEE.

Kernelized log linear models for continuous speech recognition

Large margin criteria and discriminative models are two effective improvements for HMM-based speech recognition. This paper proposed a large margin trained log linear model with kernels for CSR. To avoid explicitly computing in the high dimensional feature space and to achieve the nonlinear decision boundaries, a kernel based training and decoding framework is proposed in this work. To make the system robust to noise a kernel adaptation scheme is also presented. Previous work in this area is extended in two directions. First, most kernels for CSR focus on measuring the similarity between two observation sequences. The proposed joint kernels defined a similarity between two observation-label sequence pairs on the sentence level. Second, this paper addresses how to efficiently employ kernels in large margin training and decoding with lattices. To the best of our knowledge, this is the first attempt at using large margin kernel-based log linear models for CSR. The model is evaluated on a noise corrupted continuous digit task: AURORA 2.0. © 2013 IEEE.

Androgen receptor targets NFKB and TSPI to suppress prostate tumor growth in vivo

The androgen role in the maintenance of prostate epithelium is subject to conflicting opinions. While androgen ablation drives the regression of normal and cancerous prostate, testosterone may cause both proliferation and apoptosis. Several investigators note decreased proliferation and stronger response to chemotherapy of the prostate cancer cells stably expressing androgen receptor (AR), however no mechanistic explanation was offered. In this paper we demonstrate in vivo anti-tumor effect of the AR on prostate cancer growth and identify its molecular mediators. We analyzed the effect of AR on the tumorigenicity of prostate cancer cells. Unexpectedly, the AR-expressing cells formed tumors in male mice at a much lower rate than the AR-negative controls. Moreover, the AR-expressing tumors showed decreased vascularity and massive apoptosis. AR expression lowered the angiogenic potential of cancer cells, by increasing secretion of an anti-angiogenic protein, thrombospondin-1. AR activation caused a decrease in RelA, a subunit of the pro-survival transcription factor NF kappa B, reduced its nuclear localization and transcriptional activity. This, in turn, diminished the expression of its anti-apoptotic targets, Bcl-2 and IL-6. Increased apoptosis within AR-expressing tumors was likely due to the NF kappa B suppression, since it was restricted to the cells lacking nuclear (active) NF kappa B. Thus we for the first time identified combined decrease of NF kappa B and increased TSP1 as molecular events underlying the AR anti-tumor activity in vivo. Our data indicate that intermittent androgen ablation is preferable to continuous withdrawal, a standard treatment for early-stage prostate cancer. (C) 2007 Wiley-Liss, Inc.

AE指数的可靠性研究

Auroral electrojet index (AE) are usually used to quantitatively describe the activity of the geomagnetic field in the polar region. AE is a means to identify the level of a substorm as well. The auroral electrojet indices (AU, AL, and AE) have served well for more than four decades as measures of magnetospheric substorm activity. However, as substorm studies have progressed considerably during the past several years, the accuracy of the present electrojet indices have become an important issue. Thus it is fortunate for us to reexamine and evaluate the accuracy of the present electrojet indices and improve them if necessary. For a better use of the present indices and for future improvement we examine the limitations of the auroral electrojet indices as an accurate quantitative measure of the auroral electrojets and magnetospheric substorms. Some of the limitations arise from the data availability and also from the present simplified scheme in deriving them, but some of them originate in the definition themselves. In the present paper, we analyze the characteristics of aurora, ionospheric current system and the AE index. It is noted that for the pseudo-breakup events the variations of AE ( > 500 nT) clearly show the sudden increase and slow decrease phases. However, aurora does not expand to poleward or equatorward, and the ionospheric currents presents the features of the magnetic convection. We mainly focus on investigating what time the AE could be used to identify the subtorm.

CULTIVARES de soja convencionais: Mato Grosso safra 2010/2011.

Grupo de maturidade; Peso médio de sementes; Mancha "olho-de-rã"; Cancro da haste; Oídio; Nematóides de galhas; Cultivares de soja convencional; BRSGO 7560; BRSMG 752S; BRSGO 7960; BRS 217 [Flora]; BRSMG 68 [Vencedora]; BRSMG 810 C; MG/BR-46 Conquista; BRSGO 8360; BRS Jiripoca; BRSGO Luziâna; BRSGO Chapadões; BRSGO Jataí; BRS Pétala; BRS Gralha; BRS 252 [Serena]; BRS Aurora; BRS Raimunda.

Crias de cabras portadoras do CAEV podem nascer contaminadas.

2005

Targeting aberrant kinase activity in myeloid leukaemias

Acute myeloid leukaemia (AML) is the most common form of acute leukaemia in adults. Its treatment has remained largely unchanged for the past 30 years. Chronic myeloid leukaemia (CML) represents a tremendous success story in the era of targeted therapy but significant challenges remain including the development of drug resistance and disease persistence due to presence of CML stem cells. The Aurora family of kinases is essential for cell cycle regulation and their aberrant expression in cancer prompted the development of small molecules that selectively inhibit their activity. Chapter 2 of this thesis outlines the efficacy and mechanism of action of alisertib, a novel inhibitor of Aurora A kinase, in preclinical models of CML. Alisertib possessed equipotent activity against CML cells expressing unmutated and mutated forms of BCR-ABL. Notably, this agent retained high activity against the T315I and E255K BCR-ABL mutations, which confer the greatest degree of resistance to standard CML therapy. Chapter 3 explores the activity of alisertib in preclinical models of AML. Alisertib disrupted cell viability, diminished clonogenic survival, induced expression of the forkhead box O3 (FOXO3a) targets p27 and BCL-2 interacting mediator (BIM), and triggered apoptosis. A link between Aurora A expression and sensitivity to ara-C was established. Chapter 4 outlines the role of the proto-oncogene serine/threonine-protein (PIM) kinases in resistance to ara-C in AML. We report that the novel small molecule PIM kinase inhibitor SGI-1776 disrupted cell viability and induced apoptosis in AML. We establish a link between ara-C resistance and PIM over-expression. Finally, chapter 5 explores how the preclinical work outlined in this thesis may be translated into clinical studies that may lead to novel therapeutic approaches for patients with refractory myeloid leukaemia.

Dinámica y distribución de macro nutrientes en Nothofagus antarctica creciendo en distintas condiciones en Patagonia Sur

Nothofagus antarctica (ñire) es una de las especies forestales más importantes en abundancia en Patagonia Sur, siendo utilizado principalmente bajo sistemas silvopastoriles. En esta tesis se estudió la acumulación de biomasa y nutrientes (N, P, K, Ca, S y Mg) en componentes aéreos y subterráneos de ñire de distintas edades (5-20, 21-110 y 120-220 años), clases de copa (dominantes, codominantes, intermedios, suprimidos) y creciendo en tres calidades de sitio diferentes (alta, mediana y baja). Se encontró que la cantidad de biomasa y nutrientes varió significativamente según la edad, clase de copa y calidad de sitio, detectándose interacciones entre estos factores. Basado en un enfoque alométrico se determinó que la partición de biomasa varió según el sitio aunque no con la clase de copa, mientras que la partición de nutrientes varió significativamente con ambas. Los árboles creciendo en los mejores sitios destinaron mayor cantidad de todos los recursos hacia el componente aéreo mientras que los sitios de baja calidad incrementaron el destino hacia raíces. Los árboles dominantes destinaron mayor proporción de nutrientes hacia el componente aéreo con excepción del N, el cual fue derivado en mayor proporción hacia la parte aérea por los suprimidos. Por otra parte, se evaluó la dinámica del N en un sistema silvopastoril de ñire (1600 árboles ha-1). Se utilizó fertilizante enriquecido con 15N y se estudió su dinámica en un sistema silvopastoril (estrato herbáceo + árboles + suelo) en comparación con un pastizal abierto adyacente. El sistema silvopastoril absorbió casi tres veces más 15N que el pastizal abierto, y el estrato herbáceo absorbió casi un 70 por ciento más del fertilizante que el componente arbóreo. En conclusión, este estudio brinda información relevante y original en cuanto a dinámica y partición de recursos (biomasa y nutrientes) en ñire, y se presentan reglas alométricas como herramienta para estimaciones a futuro en diversos estudios ecológicos de ciclo de nutrientes y fertilidad mineral. Por otra parte, los resultados obtenidos indican que en sistemas silvopastoriles de ñire existiría un efecto de facilitación de N por parte del componente arbóreo hacia el estrato herbáceo, siendo estos sistemas más eficientes en la absorción y retención de N en comparación a un pastizal abierto.

La cadena agroindustrial porcina en Brasil

p.29-35

Distribución de fertilizantes marcados con 15 N en la rotación ajo - moha

p.105-110