Interference of Mycobacterium tuberculosis with macrophage responses

Tuberculosis, caused by Mycobacterium tuberculosis, has become an important health and economic burden, with more than four thousand people succumbing to the disease every day. Thus, there is an urgent need to understand the molecular basis of this pathogen's success in causing disease in humans, in order to develop new drugs superior to conventional drugs available at present. One reason why M. tuberculosis is such a dangerous microbe lies within its ability to survive within infected hosts, thereby efficiently circumventing host immune responses. Over the past few years, a number of mechanisms have been unravelled that are utilized by M. tuberculosis to survive within hosts and to avoid immune defence mechanisms. Several of these mechanisms have been described in this communication that may be useful for the development of novel compounds to treat tuberculosis

Exploring prospects of novel drugs for tuberculosis

Tuberculosis remains a disease with an enormous impact on public health worldwide. With the continuously increasing epidemic of drug-resistant tuberculosis, new drugs are desperately needed. However, even for the treatment of drug-sensitive tuberculosis, new drugs are required to shorten the treatment duration and thereby prevent development of drug resistance. Within the past ten years, major advances in tuberculosis drug research have been made, leading to a considerable number of antimycobacterial compounds which are now in the pipeline. Here we discuss a number of these novel promising tuberculosis drugs, as well as the discovery of two new potential drug targets for the development of novel effective drugs to curb the tuberculosis pandemic, ie, the coronin 1 and protein kinase G pathways. Protein kinase G is secreted by mycobacteria and is responsible for blocking lysosomal delivery within the macrophage. Coronin 1 is responsible for activating the phosphatase, calcineurin, and thereby preventing phagosome-lysosome fusion within the macrophage. Blocking these two pathways may lead to rapid killing of mycobacteri

USDA's Healthy Eating Index and Nutrition Information

A comprehensive model is developed to measure the extent that nutrition knowledge and diet-health awareness, among other factors, influence an individual's Healthy Eating Index (HEI), USDA's measure of overall diet quality. This is the first study that rigorously attempts to examine variation in the index across population groups by controlling for personal and household characteristics and nutrition information levels, as well as test for the endogeneity of nutrition information. Results indicate that one's level of nutrition information has an important influence on one's HEI and that nutrition information and the HEI are simultaneously determined. Other factors explaining variations in HEI's across individuals are income and education levels, race, ethnicity, and age. Evidence supports the hypothesis that higher education promotes more healthful food choices through better acquisition and use of health information.diet quality, Healthy Eating Index, nutrient demand, nutrition knowledge, health inputs, health production, Food Consumption/Nutrition/Food Safety,

Central polar cap convection response to short duration southward Interplanetary Magnetic Field

International audienceCentral polar cap convection changes associated with southward turnings of the Interplanetary Magnetic Field (IMF) are studied using a chain of Canadian Advanced Digital Ionosondes (CADI) in the northern polar cap. A study of 32 short duration (~1 h) southward IMF transition events found a three stage response: (1) initial response to a southward transition is near simultaneous for the entire polar cap; (2) the peak of the convection speed (attributed to the maximum merging electric field) propagates poleward from the ionospheric footprint of the merging region; and (3) if the change in IMF is rapid enough, then a step in convection appears to start at the cusp and then propagates antisunward over the polar cap with the velocity of the maximum convection. On the nightside, a substorm onset is observed at about the time when the step increase in convection (associated with the rapid transition of IMF) arrives at the polar cap boundary

A SIMPLE RP-HPLC METHOD FOR SIMULTANEOUS ESTIMATION OF ORGANIC IMPURITIES, ENANTIOMER AND ASSAY OF DEXLANSOPRAZOLE

Objective: To develop a simple and accurate RP-HPLC method for simultaneous estimation of organic impurities, enantiomer and assay of Dexlansoprazole, proposed method was validated according to an International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use (ICH) guidelines.Methods: Cellulose tris-(3,5-dichlorophenylcarbamate) bonded on silica gel (Chiralpak IC) were used as stationary phase. Acetonitrile (ACN) and 10 mM dibasic potassium phosphate buffer of pH 7.20, adjusted with dilute ortho phosphoric acid, were used as mobile phase in gradient composition at a flow rate of 1.0 ml/min. UV detection was made at 283 nm and run time was 27 min.Results: Limit of detection (LOD) and Limit of quantification (LOQ) was 42 and 126 ng/ml, respectively. Analytes response was studied from 0.25-1.50 µg/ml and r2 value of the calibration curve was>0.999. Accuracy was studied in three different concentrations, the mean recovery was observed between 93.8 and 102.5%. To the maximum of 0.01% impurity variation was observed between the results of inter and intra-day precision.Conclusion: Proposed method is specific, precise, sensitive, linear and accurate. As a significance of this proposed method, the listed known impurities of Lansoprazole monograph [United States, British and European pharmacopoeias (USP/BP/Ph. Eur.)] Were used in method development and separation was demonstrated. Apart from this, enantiomer resolution was achieved and the same chromatogram was used for assay calculation.Â

Occurrence of Hysteresis like behavior of resistance of Sb2Te3Sb_2 Te_3 film in heating-cooling cycle

Experimental observations of a peculiar behavior observed on heating and cooling ${\rm Sb_2Te_3}$ films at different heating and cooling rate are detailed. The film regained its original resistance, forming a closed loop, on the completion of the heating-cooling cycle which was reproducible for identical conditions of heating and cooling. The area enclosed by the loop was found to depend on (i) the thickness of the film, (ii) the heating rate, (iii) the maximum temperature to which film was heated and (iv) the cooling rate. The observations are explained on basis of model which considers the film to be a resultant of parallel resistances. The film's finite thermal conductivity gives rise to a temperature gradient along the thickness of the film, due to this and the temperature coefficient of resistance, the parallel combination of resistance changes with temperature. Difference in heating and cooling rates give different temperature gradient, which explains the observed hysteresis.Comment: 21 pages and 10 figure

Optimal configuration of microstructure in ferroelectric materials by stochastic optimization

An optimization procedure determining the ideal configuration at the microstructural level of ferroelectric (FE) materials is applied to maximize piezoelectricity. Piezoelectricity in ceramic FEs differ significantly from that of single crystals because of the presence of crystallites (grains) possessing crystallographic axes aligned imperfectly. The piezoelectric properties of a polycrystalline (ceramic) FE is inextricably related to the grain orientation distribution (texture). The set of combination of variables, known as solution space, which dictates the texture of a ceramic is unlimited and hence the choice of the optimal solution which maximizes the piezoelectricity is complicated. Thus a stochastic global optimization combined with homogenization is employed for the identification of the optimal granular configuration of the FE ceramic microstructure with optimum piezoelectric properties. The macroscopic equilibrium piezoelectric properties of polycrystalline FE is calculated using mathematical homogenization at each iteration step. The configuration of grains characterised by its orientations at each iteration is generated using a randomly selected set of orientation distribution parameters. Apparent enhancement of piezoelectric coefficient $d_{33}$ is observed in an optimally oriented BaTiO$_3$ single crystal. A configuration of crystallites, simultaneously constraining the orientation distribution of the c-axis (polar axis) while incorporating ab-plane randomness, which would multiply the overall piezoelectricity in ceramic BaTiO$_{3}$ is also identified. The orientation distribution of the c-axes is found to be a narrow Gaussian distribution centred around ${45^\circ}$. The piezoelectric coefficient in such a ceramic is found to be nearly three times as that of the single crystal.Comment: 11 pages, 7 figure