Cell-to-Cell Transfer of M. tuberculosis Antigens Optimizes CD4 T Cell Priming

SummaryDuring Mycobacterium tuberculosis and other respiratory infections, optimal T cell activation requires pathogen transport from the lung to a local draining lymph node (LN). However, the infected inflammatory monocyte-derived dendritic cells (DCs) that transport M. tuberculosis to the local lymph node are relatively inefficient at activating CD4 T cells, possibly due to bacterial inhibition of antigen presentation. We found that infected migratory DCs release M. tuberculosis antigens as soluble, unprocessed proteins for uptake and presentation by uninfected resident lymph node DCs. This transfer of bacterial proteins from migratory to local DCs results in optimal priming of antigen-specific CD4 T cells, which are essential in controlling tuberculosis. Additionally, this mechanism does not involve transfer of the whole bacterium and is distinct from apoptosis or exosome shedding. These findings reveal a mechanism that bypasses pathogen inhibition of antigen presentation by infected cells and generates CD4 T cell responses that control the infection

Interconverting Lanthanum Hydride and Borohydride Catalysts for C=O Reduction and C−O Bond Cleavage

The high catalytic reactivity of homoleptic tris(alkyl) lanthanum La{C(SiHMe2)3}3 is highlighted by C−O bond cleavage in the hydroboration of esters and epoxides at room temperature. The catalytic hydroboration tolerates functionality typically susceptible to insertion, reduction, or cleavage reactions. Turnover numbers (TON) up to 10 000 are observed for aliphatic esters. Lanthanum hydrides, generated by reactions with pinacolborane, are competent for reduction of ketones but are inert toward esters. Instead, catalytic reduction of esters requires activation of the lanthanum hydride by pinacolborane

Modelling of Heat Loss in Closed Vessels during propellant Burning

Closed vessel technique is essentially used to determine the force constant, vivacity and the burning rate of gun propellants. In fact, it is the only method to find out these three parameters experimentally. It is a well-known fact that however small the propellant burning time may be, there will be heat loss to the walls of the vessel due to conduction, convection, radiation and also due to the expansion of the vessel. This fact necessitates applying correction to the observed maximum pressure in the experiment. An analysis is presented in this paper as to how this heat loss can be modelled along with discussion about other models reported in this field

Effects of Different Meteorological Standards on Projectile Path

Projectile path is dictated by estimated line of fire. Line of fire can be estimated by referring RT as well as trajectory model on computer. RT is prepared under ISA/ICAO meteorological standard conditions without wind effect. Meteorological conditions like density, humidity, pressure, wind, temperature affect the path of the trajectory. Meteorological data plays very important role in trajectory prediction. Trajectory is predicted using RT for a particular weapon where ICAO standard met data is used. Ind Std met data is different from ICAO data. Use of Ind Std data improves the accuracy of trajectory prediction for Indian field deployment. In this paper, comparative study of effect on projectile path under ICAO, Ind Std and actual Indian prevailing met have been carried out and analyzed. From this analysis, a new model has been established that if actual prevailing met is not available then trajectory prediction can be carried out using Ind Std met data with wind data as perdate and time. It predicts trajectory very close to actual. Effect of wind has been studied and found that wind effect is very dominant on projectile path. Study of effect of density also has been carried out in this paper. It is observed that Ind Std density values are much close to actual as compared to ICAO. Therefore, if insufficient met is recorded then Ind std density can be used to fill density values for that region.Defence Science Journal, 2013, 63(1), pp.101-107, DOI:http://dx.doi.org/10.14429/dsj.63.264

IN-VITRO IN-VIVO STUDIES OF LAMOTRIGINE TABLETS PREPARED BY HOT MELT EXTRUSION TECHNIQUE

Objective: Present study deals with improvement in dissolution and bioavailability of poorly water soluble Lamotrigine (Lamo), an antiepileptic drug (AED) of phenyltriazine class. Formulation of poorly water soluble drug for oral delivery is one of the biggest challenge. Amongst all the approaches, the novel solid dispersion (SD) technique known as hot melt extrusion (HME) has found to be the most widely used method in improving dissolution and bioavailability.Methods: Dissolution enhancement of Lamo were done by HME technology where crystalline form of API is converted to amorphous form using hydrophilic polymer Kollidon VA64. Plasticizers like Polyethylene glycol (PEG 4000), polyoxyl 35 castor oil (Cremophor EL) and Sorbiton monolaurate (Montane 20PHA) were used. Physical blends of drug, polymer and plasticizer were prepared in the ratio of 1:1:0.1. These physical mixtures were subjected to melt and the resultant formulations were subjected to physical characterization, dissolution, permeability and in vivo testing. Pharmacokinetics of Lamo was studied in rats. Drug efflux pump like P-glycoprotein (P-gp) was recognized to posses' functional role in determining the pharmacokinetics of drugs.Results: Drug release showed the similar profile for all the HME formulations while the permeability studies showed improved permeability of formulations containing Montane 20PHA. In comparison to Non HME, HME formulations showed a significant enhancement in permeability. SD prepared by Cremophor EL resulted in 765.22% enhancement in extent of absorption.Conclusion: HME technology could be a promising formulation approach to enhance the dissolution and bioavailability of Lamo

Machine Learning Aided Static Malware Analysis: A Survey and Tutorial

Malware analysis and detection techniques have been evolving during the last decade as a reflection to development of different malware techniques to evade network-based and host-based security protections. The fast growth in variety and number of malware species made it very difficult for forensics investigators to provide an on time response. Therefore, Machine Learning (ML) aided malware analysis became a necessity to automate different aspects of static and dynamic malware investigation. We believe that machine learning aided static analysis can be used as a methodological approach in technical Cyber Threats Intelligence (CTI) rather than resource-consuming dynamic malware analysis that has been thoroughly studied before. In this paper, we address this research gap by conducting an in-depth survey of different machine learning methods for classification of static characteristics of 32-bit malicious Portable Executable (PE32) Windows files and develop taxonomy for better understanding of these techniques. Afterwards, we offer a tutorial on how different machine learning techniques can be utilized in extraction and analysis of a variety of static characteristic of PE binaries and evaluate accuracy and practical generalization of these techniques. Finally, the results of experimental study of all the method using common data was given to demonstrate the accuracy and complexity. This paper may serve as a stepping stone for future researchers in cross-disciplinary field of machine learning aided malware forensics.Comment: 37 Page

Evaluation of knowledge, attitude and behavior about rational use of medicines in second year medical students

Background: To assess the knowledge about various issues concerned with rational use of medicines in second year medical studentsMethods: This was a survey-based, cross-sectional study in which a self developed, pre-tested, semi-structured questionnaire was used. Respondents were 153 students of second year MBBS (beginning of third semester). They were explained about nature and purpose of study and necessary consent obtained. Questions were framed to obtain information about various issues concerned with use of medicines, common beliefs /misconceptions, purchase of medicines, sources of information about medicines etc. Results were expressed as counts and percentages.Results: Majority of respondents were aware about OTC (54%) and generic medicines (96.7%), importance of reading medicine label (58.8%), that medicines are not needed for every illness (86.2%), medicines manufactures by big multinational companies are not always better (67.9%). 75.8% respondents were not influenced by direct to consumer advertising for purchase of medicines and 69.9% opined that medicines obtained from government hospital are not of inferior quality. 83.6% of respondents opined that they never mixed treatment of more than one doctor at a time and 83% always purchased all medicines written in prescription. For 93.4% respondents’ doctors’ advice was the most important factor that influenced medicine purchase.Conclusion: Though majority of respondents were aware about most of the issues addressed in the questionnaire which seems to be a positive finding, those still unaware needs to be educated by adopting suitable interventions

Chandra Observations of X-ray Weak Narrow-Line Seyfert 1 Galaxies

We present Chandra observations of 17 optically-selected, X-ray weak narrow-line Seyfert 1 (NLS1) galaxies. These objects were optically identified by Williams et al. (2002) in the Sloan Digital Sky Survey Early Data Release, but were not found in the ROSAT All-Sky Survey (RASS) despite having optical properties similar to RASS-detected NLS1s. All objects in this sample were detected by Chandra and exhibit a range of 0.5-2 keV photon indices Gamma=1.1-3.4. One object was not detected in the soft band, but has a best-fit Gamma=0.25 over the full 0.5-8 keV range. These photon indices extend to values far below what are normally observed in NLS1s. A composite X-ray spectrum of the hardest objects in this sample does not show any signs of absorption, although the data do not prohibit one or two of the objects from being highly absorbed. We also find a strong correlation between Gamma and L_1keV; this may be due to differences in L_bol/L_Edd among the NLS1s in this sample. Such variations are seemingly in conflict with the current paradigm that NLS1s accrete near the Eddington limit. Most importantly, this sample shows that strong, ultrasoft X-ray emission is not a universal characteristic of NLS1s; in fact, a substantial number may exhibit weak and/or low-Gamma X-ray emission.Comment: Minor changes, added section on X-ray weakness. 25 pages incl. 6 figures, 3 tables, accepted to Ap