Biochemical and structural characterization of mycobacterial aspartyl-tRNA synthetase AspS, a promising TB drug target.

The human pathogen Mycobacterium tuberculosis is the causative agent of pulmonary tuberculosis (TB), a disease with high worldwide mortality rates. Current treatment programs are under significant threat from multi-drug and extensively-drug resistant strains of M. tuberculosis, and it is essential to identify new inhibitors and their targets. We generated spontaneous resistant mutants in Mycobacterium bovis BCG in the presence of 10× the minimum inhibitory concentration (MIC) of compound 1, a previously identified potent inhibitor of mycobacterial growth in culture. Whole genome sequencing of two resistant mutants revealed in one case a single nucleotide polymorphism in the gene aspS at 535GAC>535AAC (D179N), while in the second mutant a single nucleotide polymorphism was identified upstream of the aspS promoter region. We probed whole cell target engagement by overexpressing either M. bovis BCG aspS or Mycobacterium smegmatis aspS, which resulted in a ten-fold and greater than ten-fold increase, respectively, of the MIC against compound 1. To analyse the impact of inhibitor 1 on M. tuberculosis AspS (Mt-AspS) activity we over-expressed, purified and characterised the kinetics of this enzyme using a robust tRNA-independent assay adapted to a high-throughput screening format. Finally, to aid hit-to-lead optimization, the crystal structure of apo M. smegmatis AspS was determined to a resolution of 2.4 Å

General specifications for a captive power driven compressors and dryer system

Design, Construction, Manufacture, Supply to, Erection, Testing, Commissioning of the captive power driven compressors and dryer system (CPDCDS

Mild Functional Ischemic Mitral Regurgitation Following Acute Coronary Syndrome: A Retrospective Study

Background: Ischemic mitral regurgitation is a frequent complication of acute coronary syndrome. It primarily occurs in patients with a prior myocardial infarction but also may be seen with acute ischemia, a setting in which the MR typically resolves after the ischemia resolves.none The vast majority of patients have "functional" ischemic MR. In these individuals, the papillary muscles, chordae, and valve leaflets are normal. However, the leaflets do not coapt and restricted leaflet motion is frequently noted on echocardiography. Ischemic mitral regurgitation indicates a poor prognosis after acute myocardial infarction. This study addresses the clinical characteristics of patients of acute coronary syndrome with mild functional ischemic mitral regurgitation and its impact on immediate in-hospital cardiovascular outcomes and death. Patients and Methods: From March 2006 through May 2007, patients who underwent 2-dimensional (2D) color doppler echocardiographic quantification of ischemic mitral regurgitation within 10 days of admission for acute coronary syndrome (ACS) in Manipal Teaching Hospital, a tertiary hospital in the western region of Nepal were noted. The demographic details, conventional risk factors of coronary artery disease, clinical and laboratory findings, treatment course and in-hospital outcomes of all the patients with mild functional ischemic MR following ACS in that time duration were recorded in a designated Performa. A total of 94 patients enrolled in the study were divided into two groups: Group I with mild functional ischemic MR and Group II without MR on 2D echocardigraphic assessment. Patient characteristics, risk factors, ejection fraction, and cardiovascular outcome and death among the two groups were compared and analyzed using software package SPSS 17.0 version. Results : Group I constituted 64.89% of the study population and Group II comprised of 35.11%. The patients in Group I was more likely to be elderly diabetic (P<0.05), and smokers with hypertension (P < 0.05). Mild functional ischemic MR was more common in patients with STEMI as compared to those with unstable angina and NSTEMI (55.7%, 36.1%, and 8.2%; P < 0.05).The mean ejection fraction in the first group was 54.84% in contrast to 58.92% observed in group II (P < 0.05).The type of wall involvement inferred from EKG analysis was homogeneously distributed in both the groups. Finally, there was no difference in immediate in-hospital (within 10 days) mortality or cardiovascular outcomes (heart failure, ventricular tachycardia/fibrillation, hypotension, and cardiogenic shock) between these two groups. Conclusion: Ischemic mitral regurgitation following acute coronary syndromeare more likely in elderly diabetics and hypertensive smokers. It is a more common finding in STEMI. Although mild MR following ACS does reduce ejection fraction, the immediate (within 10 days) in-hospital mortality and cardiovascular outcomes are not significantly altered

A Review on the Classifications of Organic/Inorganic/Carbonaceous Hole Transporting Materials for Perovskite Solar Cell Application

The rapid increase in the efficiency of perovskite solar cells (PSCs) in last few decades have made them very attractive to the photovoltaic (PV) community. However, the serious challenge is related to the stability under various conditions and toxicity issues. A huge number of articles have been published in PSCs in the recent years focusing these issues by employing different strategies in the synthesis of electron transport layer (ETL), active perovskite layer, hole transport layer (HTL) and back contact counter electrodes. This article tends to focus on the role and classification of different materials used as HTL in influencing long-term stability, in improving the photovoltaic parameters and thereby enhancing the device efficiency. Hole Transport Materials (HTMs) are categorized by dividing into three primary types, namely; organic, inorganic and carbonaceous HTMs. To analyze the role of HTM in detail, we further divide these primary type of HTMs into different subgroups. The organic-based HTMs are subdivided into three categories, namely; long polymer HTMs, small molecule HTMs and cross-linked polymers and the inorganic HTMs have been classified into nickel (Ni) derivatives and copper (Cu) derivatives based HTMs, p-type semiconductor based HTMs and transition metal based HTMs. We further analyze the dual role of carbonaceous materials as HTM and counter electrode in the perovskite devices. In addition, in this review, an overview of the preparation methods, and the influence of the thickness of the HTM layers on the performance and stability of the perovskite devices are also provided. We have carried out a detailed comparison about the various classification of HTMs based on their cost-effectiveness and considering their role on effective device performance. This review further discusses the critical challenges involved in the synthesis and device engineering of HTMs. This will provide the reader a better insight into the state of the art of perovskite solar devices

Patient-adjusted deep-brain stimulation programming is time saving in dystonia patients

Deep-brain stimulation (DBS) programming for dystonia patients is a complex and time-consuming task

Structures of different LOS subclasses from <i>M</i>. <i>kansasii</i>

<p>(A) LOS-I-III (n = 1–3), (B) LOS-IV-VII (n = 2–4), (C) LOS-VII; R1, R2 and R3 represents the acyl chain attached to tetra glucose core of LOS. (D) Schematic showing predicted domains and topology of <i>MKAN27435</i>. The amino and carboxy terminals are indicated as ‘N’ and ‘C’ respectively, and numbers represent predicted borders of domains which are depicted as grey areas. The regions corresponding to the predicted transmembrane domains are indicated with black bars.</p