Generation of gravity waves in an experimental facility

The development of a computational tool to study the propagation of gravity waves in water is carried out by reproducing the conditions of an experimental study. The problem consists in the propagation of a gravity wave in a channel with a bottom topography where the is already a mean flow in the opposite direction. The physics of such problem is analogous to the one involved in the Hawking radiation of a black hole, which stresses the practical importance of the computational tool being developed, given that black holes are phenomena difficult for us to study. The problem will be analyzed with both a theoretical and a numerical approach. The numerical simulations will be performed by means of the software Gerris. As a first approach, a simpler version of the problem in which the channel is straight is analyzed. From the theoretical point of view, in these conditions and under some assumptions about the nature of the flow, the equations describing the motion of the fluid (Navier-Stokes equations) can be simplified up to a linear theory which provides an analytical solution. The analytical linear results are then contrasted with those obtained with a numerical simulation in order to check the validity of the latter. Once this step is accomplished, the actual problem of a flow in channel with a bottom topography will be studied by means of a numerical simulation, using the same computational methodology. The results obtained will be compared to those obtained in the experimental study mentioned earlier. The aim of this project is to implement a numerical tool that allows us to investigate up to which point the experimental analogy between gravity waves propagating against a flume in a channel of variable depth and the Hawking radiation of a black hole is applicable. The computational tool we will derive can be later extended to the study of the propagation of water gravity waves in flows under different conditions.Ingeniería Aeroespacia

Proteomic approach in the search of new cardiovascular biomarkers

Proteomic approach in the search of new cardiovascular biomarkers With the increasing incidence of cardiovascular diseases worldwide, specifically atherosclerosis and heart failure, the search for novel biomarkers remains a priority. As opposed to complex diagnostic techniques that may not be suitable to be applied to the wider population, biomarkers are useful for population screening. The search for novel biomarkers is based on knowledge of the molecular and cellular processes that take place in the development of a specific disease. Atherosclerosis and heart failure are characterized by a long period of silent disease progression, allowing early diagnosis and the potential of early therapeutic intervention. The use of the so-called proteomic techniques allows not only protein identification but partial characterization, which includes expression and also post-translational modification of these proteins. This allows for the discovery of previously unknown proteins involved in cardiovascular diseases, including some that may be suitable to be used as biomarkers. However, to approach this issue, we have to overcome difficulties such as tissue heterogeneity (vessel wall or myocardium) and the lack of fresh human samples. We discuss the proteomic study of human plaques, secreted proteins by pathologic and normal vessel wall, and left ventricular hypertrophy as potential sources of new biologic markers of cardiovascular disease

Easy-To-Synthesize Spirocyclic Compounds Possess Remarkable in Vivo Activity against Mycobacterium tuberculosis

Society urgently needs new, effective medicines for the treatment of tuberculosis. To kick-start the required hit-to-lead campaigns, the libraries of pharmaceutical companies have recently been evaluated for starting points. The GlaxoSmithKline (GSK) library yielded many high-quality hits, and the associated data were placed in the public domain to stimulate engagement by the wider community. One such series, the spiro compounds, are described here. The compounds were explored by a combination of traditional in-house research and open source methods. The series benefits from a particularly simple structure and a short associated synthetic chemistry route. Many members of the series displayed striking potency and low toxicity, and highly promising in vivo activity in a mouse model was confirmed with one of the analogues. Ultimately the series was discontinued due to concerns over safety, but the associated data remain public domain, empowering others to resume the series if the perceived deficiencies can be overcome

Contemplata : momentos místicos

Ante

Diversification and Development of Spiros Compounds for the Treatment of Tuberculosis

This thesis reports the synthesis and biological evaluation of novel molecules intended for the treatment of tuberculosis. Tuberculosis is a dangerous infectious disease caused by the bacterium Mycobacterium tuberculosis, which if not treated or treated inefficiently can be fatal. It was estimated that in 2012 tuberculosis was responsible for the death of 1.3 million people and the infection of 8.6 million more. The current treatment for tuberculosis consists of a combination of drugs, which typically involve excessively long term treatments, resulting in many cases in the partial completion of the treatment. In recent years multi– and extensively drug resistant strains have evolved. New drugs with new mechanisms of action are urgently needed. The anti–tubercular drug pipeline is weak, with few new chemical entities currently in clinical trials. In an attempt to fulfil this need, GlaxoSmithKline recently reported several new chemical series with potential for the treatment of TB. One, based on a thiophene spirocycle core, and named the Spiros family, was found to inhibit the growth of Mycobacterium tuberculosis through a different mechanism of action from any other approved anti–tubercular drug. A synthesis of this Spiros family has recently been developed via a three-steps oxa–Pictet–Spengler reaction, and several members of this family have exhibited potency vs. virulent strains of TB. This thesis reports the synthesis of several novel compounds with variation in the heterocyclic ring of the Spiros family, a portion of the molecule that has not been explored to date. The oxa–Pictet–Spengler reaction was used as the key transformation of this reaction, tolerating a range of aromatic heterocycles. Initial biological activity data for the compounds synthesised were obtained, indicating promising levels of potency comparable with already-reported analogs in this series vs. the virulent strain of TB. It was found that potent anti-TB molecules are available in one chemical step from commercial materials