High-throughput drug screen to identify compounds working selectively and synergistically with CQ to inhibit proliferation of TSC-2 deficient cells

Tuberous sclerosis complex (TSC) is a multisystem genetic disease that is caused by a germ line mutation in the genes TSC1 and TSC2. Patients with the disease tend to suffer from benign tumors of the brain, heart, kidneys, skin, and other organs that contain giant cells. Although mTORC1 inhibitors (rapamycin and rapalogs) are often used to treat TSC because of their efficacy in promoting tumor shrinkage, clinical studies in the past have shown that when treatment is taken away, the tumor size returns to its original state. The objective of this study was to identify compounds that selectively inhibit proliferation of TSC2-deficient cells. A high-throughput screen of about 4000 compounds was performed using a lysosomal inhibitor (chloroquine [CQ], 5 μM) and a “repurposing” library of compounds. Through some yet to be determined mechanism, the combination of ritanserin (a selective serotonin reuptake inhibitor [SSRI]) and chloroquine was found to synergize to selectively inhibit the cell viability of DJK MEFs and TSC2-/-KO cells (TFFs) starting at 48 hours after treatment. The effects of this combination treatment were confirmed in a second cell line (TFFs) exhibiting similar reduction in proliferation. Interestingly, treatment with CQ (5 μM) and ritanserin (20 μM) showed synergistic action (combination index [CI] = 0.6) against TSC2-deficient cells. This combination treatment induced apoptosis (41%) in TSC2-deficient cells but not in TSC2-expressing cells. These results suggest a novel treatment approach in tuberous sclerosis complex and provide an incentive for further investigation of the mechanisms contributing to the vulnerability of TSC2-deficient cells. Moreover, the use of an already Food and Drug Administration (FDA)-approved compound can lead to a more rapid pharmacologic approach for TSC patients

Reír o no reír: (meta)humorismo y violencia en la literatura contemporánea de Colombia y México

Humor can be underestimated, but to laugh or not to laugh is as transcendental as the decision to be or not to be. That is the question of this dissertation: the productive encounter of challenging instances of humor in Latin-American literary texts that not only display humor in charged violent backgrounds, but create humorous traps and spaces for meta-humorist reflections, inviting the reader to judge whether to laugh or not to laugh in an aesthetic and ethical sense. Those instances of perplexity would ask the reader to reflect on the nature of the humor displayed, its targets, context, refinement, creativity, meaning and outcomes, among other questions that laugher implies. This would foster a more solicitous public who recognizes a liberating good laugh from a violent one, avoiding the reproduction of stereotypes, hate speeches or the consent of an oppressive status quo.Romance Languages and Literature

Spatio-temporal covariance descriptors for action and gesture recognition

We propose a new action and gesture recognition method based on spatio-temporal covariance descriptors and a weighted Riemannian locality preserving projection approach that takes into account the curved space formed by the descriptors. The weighted projection is then exploited during boosting to create a final multiclass classification algorithm that employs the most useful spatio-temporal regions. We also show how the descriptors can be computed quickly through the use of integral video representations. Experiments on the UCF sport, CK+ facial expression and Cambridge hand gesture datasets indicate superior performance of the proposed method compared to several recent state-of-the-art techniques. The proposed method is robust and does not require additional processing of the videos, such as foreground detection, interest-point detection or tracking

MRF-based background initialisation for improved foreground detection in cluttered surveillance videos

Robust foreground object segmentation via background modelling is a difficult problem in cluttered environments, where obtaining a clear view of the background to model is almost impossible. In this paper, we propose a method capable of robustly estimating the background and detecting regions of interest in such environments. In particular, we propose to extend the background initialisation component of a recent patch-based foreground detection algorithm with an elaborate technique based on Markov Random Fields, where the optimal labelling solution is computed using iterated conditional modes. Rather than relying purely on local temporal statistics, the proposed technique takes into account the spatial continuity of the entire background. Experiments with several tracking algorithms on the CAVIAR dataset indicate that the proposed method leads to considerable improvements in object tracking accuracy, when compared to methods based on Gaussian mixture models and feature histograms

Numerical simulation of the inlet channel geometry influence in the torque generated at the gravitation water vortex turbine

The gravitational water vortex turbine is presented as an alternative for electric power generation for both low head and water flow conditions, additionally it is easy and low cost to implement and maintenance. However, the experimentally reported efficiencies motivate the scientific community to develop new geometries in order to improve its performance. First, it is not clear how the efficiency of the turbine is obtained and second, not all studies report it. The turbine is mainly made up of a tank, the rotor and the electric generator. The geometry of the tank is important because it stabilizes the fluid and in this component that the generation of the vortex is induced, which determines, added to other factors like tank geometry and runner, the global efficiency of the turbine. The primary purpose of this study is to compare numerically the torque generated at six (6) geometrical configurations of the basin inlet channel for Gravitational Vortex Turbine (GVT) with a Savonius rotor. The study was developed in ANSYS® CFX, where a transient state VOF model was configured with a BSL K − ω turbulence model and a discretization a discretization of the control volume made in the ICEM module. The highest torque was 0.553 Nm at 25 rpm for the trapezoidal curved inlet channel geometry, increasing the efficiency respect to the conventional Square inlet channel of the 2.73 %. The increase of tangential velocity contributes positively to the vortex generation, and consequently, an increase in torque is obtained. On the other hand, the design of the rotor considerably affects the performance of the GVT, where it may or may not take advantage of the kinetic energy of the vorte

Relation Between Mechanical Properties and 3D Printer Configurations Parameters Using PLA at Open-Source Prusa I3

This paper presents an experimental study on specimens made with the additive manufacturing (AM) Fused Deposition Material (FDM) technique with PLA material. Several configurations of geometry and printing temperature were made in order to evaluate these parameters over a tensile test. The geometry of the specimen was fabricated according to the ASTM D638 and the curvature of fillet radius were varied (76-std, 144, 244mm and straight) to obtain optimal fillet radius for tensile test. The nozzle temperature was varied (200, 210, 220 and 230°C) to show its influence on PLA stress-strain behavior. Results have shown that the fillet radius of the specimen and the printer parameters affect material quantity deposited during 3D printing process, leaving to progressive damage areas. Better performance was obtained at 210 °C printing temperature with a fillet radius of 144 mm. A modification geometry specimen were proposed in order to change the increase Z nozzle level point that generates a stress concentrator at the specimen avoiding failure zone at calibrating length of the specimen

Asymmetric effects of monetary policy on the Colombian house prices

En este artículo se examinan los efectos asimétricos que tiene la política monetaria sobre la dinámica asociada a la tasa de crecimiento de las viviendas. Se estima un modelo Markov Switching utilizando datos mensuales entre 1994 y 2015 para las tasas de crecimiento asociadas a los precios de las viviendas en Colombia. Los resultados empíricos sugieren que la tasa de crecimiento de estos precios tiene una disminución mayor ante la implementación de una política monetaria contractiva en períodos de alta volatilidad frente a aquellos donde hay calma financiera, sin ser estos tan persistentes como los asociados al caso con menor volatilidad. Lo anterior sugiere que la política monetaria es más efectiva para disminuir el crecimiento en los precios de las viviendas en períodos de crisis que en aquellos en los que las condiciones económicas son más favorables.This article examines asymmetric effects of monetary policy on real estate price growth dynamics. We estimate a Markov Switching model using monthly data from 1994 to 2015 for the Colombian house prices growth rates. Empirical results suggest that housing price growth has a larger magnitude decrease with a contractionary monetary shock in higher volatility periods than during calm ones, but is not as persistently as in less volatile ones. This suggests that monetary policy is more effective in terms of reducing housing price growths during crisis periods than those when economic conditions are more favorable.Magíster en EconomíaMaestrí

Improving representation and classification of image and video data for surveillance applications

Due to global security issues, the use of surveillance cameras has increased dramatically over the last decade. However, security cameras have not been altogether successful for preventing crime, mainly because the security videos are monitored by human operators who can become tired and distracted. Automatic visual surveillance systems have great potential for overcoming the bottleneck caused by humans in the surveillance process. A typical surveillance system includes four modules: (i) foreground extraction, (ii) object detection, (iii) tracking, and (iv) scene analysis. The main aim of this thesis is to contribute towards automatic visual surveillance. We approach this by identifying potential areas of improvement in three of the above modules. First, for the foreground extraction module we recognise shadow removal as the best way of improving the results of current foreground extraction methods, which in turn helps with object detection and tracking. Second, in the case of object detection, as humans are the main objects of interest in surveillance applications, we focu

Improved shadow removal for robust person tracking in surveillance scenarios

Shadow detection and removal is an important step employed after foreground detection, in order to improve the segmentation of objects for tracking. Methods reported in the literature typically have a significant trade-off between the shadow detection rate (classifying true shadow areas as shadows) and the shadow discrimination rate (discrimination between shadows and foreground). We propose a method that is able to achieve good performance in both cases, leading to improved tracking in surveillance scenarios. Chromacity information is first used to create a mask of candidate shadow pixels, followed by employing gradient information to remove foreground pixels that were incorrectly included in the mask. Experiments on the CAVIAR dataset indicate that the proposed method leads to considerable improvements in multiple object tracking precision and accuracy. © 2010 IEE

Asymmetric effects of monetary policy on the Colombian house prices

En este artículo se examinan los efectos asimétricos que tiene la política monetaria sobre la dinámica asociada a la tasa de crecimiento de las viviendas. Se estima un modelo Markov Switching utilizando datos mensuales entre 1994 y 2015 para las tasas de crecimiento asociadas a los precios de las viviendas en Colombia. Los resultados empíricos sugieren que la tasa de crecimiento de estos precios tiene una disminución mayor ante la implementación de una política monetaria contractiva en períodos de alta volatilidad frente a aquellos donde hay calma financiera, sin ser estos tan persistentes como los asociados al caso con menor volatilidad. Lo anterior sugiere que la política monetaria es más efectiva para disminuir el crecimiento en los precios de las viviendas en períodos de crisis que en aquellos en los que las condiciones económicas son más favorables.This article examines asymmetric effects of monetary policy on real estate price growth dynamics. We estimate a Markov Switching model using monthly data from 1994 to 2015 for the Colombian house prices growth rates. Empirical results suggest that housing price growth has a larger magnitude decrease with a contractionary monetary shock in higher volatility periods than during calm ones, but is not as persistently as in less volatile ones. This suggests that monetary policy is more effective in terms of reducing housing price growths during crisis periods than those when economic conditions are more favorable