Protease inhibitor 15, a candidate gene for abdominal aortic internal elastic lamina ruptures in the rat

The inbred Brown Norway (BN) rat develops spontaneous ruptures of the internal elastic lamina (RIEL) of the abdominal aorta (AA) and iliac arteries. Prior studies with crosses of the BN/Orl RJ (susceptible) and LOU/M (resistant) showed the presence of a significant QTL on chromosome 5 and the production of congenic rats proved the involvement of this locus. In this study, we further dissected the above-mentioned QTL by creating a new panel of LOU.BN(chr5) congenic and sub-congenic lines and reduced the locus to 5.2 Mb. Then 1002 HS rats were studied, whose phenotyping revealed a low prevalence and high variability for RIEL. High resolution mapping in the HS panel detected the major locus on chromosome 5 (log P>35) and refined it to 1.4Mb. Subsequently, RNA-seq analysis on AA of BN, congenics and LOU revealed expression differences for only protease inhibitor15 (Pi15) gene and a putative long intergenic noncoding RNA (lincRNA) within the linkage region. The high abundance of lincRNA with respect to reduced Pi15 expression, in conjunction with exertion of longitudinal strain, may be related to RIEL, indicating the potential importance of proteases in biological processes related to defective aortic IEL structure. Similar mechanisms may be involved in aneurysm initiation in the human AA

Variation in nucleotide homology obtained by amplification, cloning and sequencing of complete S1 gene from field samples of avian infectious bronchitis virus.

Projeto/Plano de Ação: 02.09.01.030

Numerical Analysis of an Overtopping Wave Energy Converter Subjected to the Incidence of Irregular and Regular Waves from Realistic Sea States

The present study aims to evaluate the difference in the fluid-dynamic behavior of an overtopping wave energy converter under the incidence of irregular waves based on a realistic sea state when compared to the incidence of regular waves, representative of this sea state. Thus, the sea data of three regions from the Rio Grande do Sul coast, Brazil, were considered. Fluent software was employed for the computational modeling, which is based on the finite volume method (FVM). The numerical generation of waves occurred through the imposition of the velocity boundary conditions using transient discrete values through the WaveMIMO methodology. The volume of fluid (VOF) multiphase model was applied to treat the water–air interaction. The results for the water amount accumulated in the device reservoir showed that the fluid-dynamic behavior of the overtopping converter has significant differences when comparing the two proposed approaches. Differences up to 240% were found for the water mass accumulated in the overtopping device reservoir, showing evidence that the results can be overestimated when the overtopping device is analyzed under the incidence of the representative regular waves. Furthermore, for all studied cases, it was possible to approximate the water volume accumulated over time in the overtopping reservoir through a first-degree polynomial function

Enhanced recovery after surgery: are we ready, and can we afford not to implement these pathways for patients undergoing radical cystectomy?

Enhanced recovery after surgery (ERAS) for radical cystectomy seems logical, but our study has shown a paucity in the level of clinical evidence. As part of the ERAS Society, we welcome global collaboration to collect evidence that will improve patient outcomes

Numerical Relativity Using a Generalized Harmonic Decomposition

A new numerical scheme to solve the Einstein field equations based upon the generalized harmonic decomposition of the Ricci tensor is introduced. The source functions driving the wave equations that define generalized harmonic coordinates are treated as independent functions, and encode the coordinate freedom of solutions. Techniques are discussed to impose particular gauge conditions through a specification of the source functions. A 3D, free evolution, finite difference code implementing this system of equations with a scalar field matter source is described. The second-order-in-space-and-time partial differential equations are discretized directly without the use first order auxiliary terms, limiting the number of independent functions to fifteen--ten metric quantities, four source functions and the scalar field. This also limits the number of constraint equations, which can only be enforced to within truncation error in a numerical free evolution, to four. The coordinate system is compactified to spatial infinity in order to impose physically motivated, constraint-preserving outer boundary conditions. A variant of the Cartoon method for efficiently simulating axisymmetric spacetimes with a Cartesian code is described that does not use interpolation, and is easier to incorporate into existing adaptive mesh refinement packages. Preliminary test simulations of vacuum black hole evolution and black hole formation via scalar field collapse are described, suggesting that this method may be useful for studying many spacetimes of interest.Comment: 18 pages, 6 figures; updated to coincide with journal version, which includes some expanded discussions and a new appendix with a stability analysis of a simplified problem using the same discretization scheme described in the pape

Genetical genomics: spotlight on QTL hotspots

No abstract available

Study Protocol: insulin and its role in cancer

<p>Abstract</p> <p>Background</p> <p>Studies have shown that metabolic syndrome and its consequent biochemical derangements in the various phases of diabetes may contribute to carcinogenesis. A part of this carcinogenic effect could be attributed to hyperinsulinism. High levels of insulin decrease the production of IGF-1 binding proteins and hence increase levels of free IGF-1. It is well established that bioactivity of free insulin growth factor 1 (IGF-1) increases tumor turnover rate. The objective is to investigate the role of insulin resistance/sensitivity in carcinogenesis by studying the relation between insulin resistance/sensitivity and IGF-1 levels in cancer patients. We postulate that hyperinsulinaemia which prevails during initial phases of insulin resistance (condition prior to overt diabetes) increases bioactivity of free IGF-1, which may contribute to process of carcinogenesis.</p> <p>Methods/Design</p> <p>Based on our pilot study results and power analysis of the same, we have designed a two group case-control study. 800 proven untreated cancer patients (solid epithelial cell tumors) under age of 50 shall be recruited with 200 healthy subjects serving as controls. Insulin resistance/sensitivity and free IGF-1 levels shall be determined in all subjects. Association between the two parameters shall be tested using suitable statistical methods.</p> <p>Discussion</p> <p>Well controlled studies in humans are essential to study the link between insulin resistance, hyperinsulinaemia, IGF-1 and carcinogenesis. This study could provide insights to the role of insulin, insulin resistance, IGF-1 in carcinogenesis although a precise role and the extent of influence cannot be determined. In future, cancer prevention and treatment strategies could revolve around insulin and insulin resistance.</p