Role of a Conserved Glutamate Residue in the \u3cem\u3eEscherichia coli\u3c/em\u3e SecA ATPase Mechanism

Escherichia coli SecA uses ATP to drive the transport of proteins across cell membranes. Glutamate 210 in the “DEVD” Walker B motif of the SecA ATP-binding site has been proposed as the catalytic base for ATP hydrolysis (Hunt, J. F., Weinkauf, S., Henry, L., Fak, J. J., McNicholas, P., Oliver, D. B., and Deisenhofer, J. (2002) Science 297, 2018–2026). Consistent with this hypothesis, we find that mutation of glutamate 210 to aspartate results in a 90-fold reduction of the ATP hydrolysis rate compared with wild type SecA, 0.3 s–1versus 27 s–1, respectively. SecA-E210D also releases ADP at a slower rate compared with wild type SecA, suggesting that in addition to serving as the catalytic base, glutamate 210 might aid turnover as well. Our results contradict an earlier report that proposed aspartate 133 as the catalytic base (Sato, K., Mori, H., Yoshida, M., and Mizushima, S. (1996) J. Biol. Chem. 271, 17439–17444). Re-evaluation of the SecA-D133N mutant used in that study confirms its loss of ATPase and membrane translocation activities, but surprisingly, the analogous SecA-D133A mutant retains full activity, revealing that this residue does not play a key role in catalysis

High-Speed Real-Time Simulators for Engineering Design

The use of computer simulations is now an established technique in engineering design. Many of these simulations are used to predict the expected behavior of systems that are not yet built, or of existing systems in modes of operation, such as catastrophic failure, in which it is not feasible to test the real system. Another use of computer simulations is for training and testing purposes in which the simulation is interfaced to real hardware, software and/or a human operator and is required to operate in real-time. Examples are plant simulators for operator training or simulated environments for testing hardware or software components. The primary requirement of a real-time simulation is that it must complete all the calculations necessary to update the simulator outputs as well as all the necessary data I/O within the allotted frame time. Many real-time simulations use frame times in the range of a few milliseconds and greater.There is an increasing number of applications, for example in power electronics and automotive systems, in which much shorter frame rates are required. This paper reviews some of these applications and the approaches to real-time simulation that can achieve frame times in the range 5 to 100 microseconds.

Comparison of the spatial QRS-T angle derived from digital ECGs recorded using conventional electrode placement with that derived from Mason-Likar electrode position

Background: The spatial QRS-T angle is ideally derived from orthogonal leads. We compared the spatial QRS-T angle derived from orthogonal leads reconstructed from digital 12-lead ECGs and from digital Holter ECGs recorded with the Mason-Likar (M-L) electrode positions. Methods and results: Orthogonal leads were constructed by the inverse Dower method and used to calculate spatial QRS-T angle by (1) a vector method and (2) a net amplitude method, in 100 volunteers. Spatial QRS-T angles from standard and M-L ECGs differed significantly (57° ± 18° vs 48° ± 20° respectively using net amplitude method and 53° ± 28° vs 48° ± 23° respectively by vector method; p < 0.001). Difference in amplitudes in leads V4–V6 was also observed between Holter and standard ECGs, probably due to a difference in electrical potential at the central terminal. Conclusion: Mean spatial QRS-T angles derived from standard and M-L lead systems differed by 5°–9°. Though statistically significant, these differences may not be clinically significant

Voltage Stability Analysis of Grid-Connected Wind Farms with FACTS: Static and Dynamic Analysis

Recently, analysis of some major blackouts and failures of power system shows that voltage instability problem has been one of the main reasons of these disturbances and networks collapse. In this paper, a systematic approach to voltage stability analysis using various techniques for the IEEE 14-bus case study, is presented. Static analysis is used to analyze the voltage stability of the system under study, whilst the dynamic analysis is used to evaluate the performance of compensators. The static techniques used are Power Flow, V–P curve analysis, and Q–V modal analysis. In this study, Flexible Alternating Current Transmission system (FACTS) devices- namely, Static Synchronous Compensators (STATCOMs) and Static Var Compensators (SVCs) - are used as reactive power compensators, taking into account maintaining the violated voltage magnitudes of the weak buses within the acceptable limits defined in ANSI C84.1. Simulation results validate that both the STATCOMs and the SVCs can be effectively used to enhance the static voltage stability and increasing network loadability margin. Additionally, based on the dynamic analysis results, it has been shown that STATCOMs have superior performance, in dynamic voltage stability enhancement, compared to SVCs

Program Synthesis using Natural Language

Interacting with computers is a ubiquitous activity for millions of people. Repetitive or specialized tasks often require creation of small, often one-off, programs. End-users struggle with learning and using the myriad of domain-specific languages (DSLs) to effectively accomplish these tasks. We present a general framework for constructing program synthesizers that take natural language (NL) inputs and produce expressions in a target DSL. The framework takes as input a DSL definition and training data consisting of NL/DSL pairs. From these it constructs a synthesizer by learning optimal weights and classifiers (using NLP features) that rank the outputs of a keyword-programming based translation. We applied our framework to three domains: repetitive text editing, an intelligent tutoring system, and flight information queries. On 1200+ English descriptions, the respective synthesizers rank the desired program as the top-1 and top-3 for 80% and 90% descriptions respectively

Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis

Background A non-invasive method to grade the severity of steatohepatitis and liver fibrosis is magnetic resonance imaging (MRI) based corrected T1 (cT1). We aimed to identify genetic variants influencing liver cT1 and use genetics to understand mechanisms underlying liver fibroinflammatory disease and its link with other metabolic traits and diseases. Methods First, we performed a genome-wide association study (GWAS) in 14,440 Europeans in UK Biobank with liver cT1 measures. Second, we explored the effects of the cT1 variants on liver blood tests, and a range of metabolic traits and diseases. Third, we used Mendelian randomisation to test the causal effects of 24 predominantly metabolic traits on liver cT1 measures. Results We identified six independent genetic variants associated with liver cT1 that reached GWAS significance threshold (p<5x10-8). Four of the variants (rs75935921 in SLC30A10, rs13107325 in SLC39A8, rs58542926 in TM6SF2, rs738409 in PNPLA3) were also associated with elevated transaminases and had variable effects on liver fat and other metabolic traits. Insulin resistance, type 2 diabetes, non-alcoholic fatty liver and BMI were causally associated with elevated cT1 whilst favourable adiposity (instrumented by variants associated with higher adiposity but lower risk of cardiometabolic disease and lower liver fat) was found to be protective. Conclusion The association between two metal ion transporters and cT1 indicates an important new mechanism in steatohepatitis. Future studies are needed to determine whether interventions targeting the identified transporters might prevent liver disease in at risk individuals

Evaluation of Machine Learning Methods to Predict Coronary Artery Disease Using Metabolomic Data

Metabolomic data can potentially enable accurate, non-invasive and low-cost prediction of coronary artery disease. Regression-based analytical approaches however might fail to fully account for interactions between metabolites, rely on a priori selected input features and thus might suffer from poorer accuracy. Supervised machine learning methods can potentially be used in order to fully exploit the dimensionality and richness of the data. In this paper, we systematically implement and evaluate a set of supervised learning methods (L1 regression, random forest classifier) and compare them to traditional regression-based approaches for disease prediction using metabolomic data

EVALUATION OF IN VITRO ANTICANCER ACTIVITY OF SYMPLOCOS RACEMOSA BARK AGAINST HEPATOCELLULAR CARCINOMA

Objective: To investigate in vitro anticancer activity of different extracts of bark of Symplocos racemosa against hepatocellular carcinoma.Methods: Different successive extracts of Symplocos racemosa bark were prepared using hexane, chloroform, ethyl acetate, n-butanol and water and were tested in vitro for cytotoxicity using (3-4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay in rat normal liver cells (BRL-3A) and human hepatocellular carcinoma (Hep3B) cells.Results: Ethyl acetate and chloroform extract of Symplocos racemosa exhibited cytotoxicity against human hepatocellular carcinoma (Hep3B) cells in vitro with IC50 value (µg/ml) of 63.45 and 75.55 respectively and not affected the normal liver (BRL-3A) cells.Conclusion: Symplocos racemosa bark extracts showed potential cytotoxic effects on human hepatocellular carcinoma cells. The anticancer activity exhibited by ethyl acetate and chloroform extract might be due to presence of phenolics and flavonoid constituents present in the bark. Ethyl acetate extract can further be explored for possible cytotoxic activity using in vivo models of liver cancer.Â

High strength stainless steel 14301 for prestressed concrete structures protection

High Strength Stainless Steels (HSSS) are being developed with the aim to improve corrosion resistance of prestressed concrete structures in aggressive environments. In the present paper focus is given to mechanical and corrosion performance of a HSSS type 14301. The ability of passivation in alkaline media and the risk of local corrosion (pitting) in presence of chlorides, has been determined. Besides, the response of the stainless steel submitted to mechanical strains similar to those in service is considered with respect to the risk of corrosion, Stress Corrosion Cracking (SCC) and Hydrogen Embrittlement (HE). The cold-drawn HSSS 14301 shows higher tolerance to chloride ion than conventional prestressing steel. The local corrosion becomes significant for chloride contents above 0.75 M. The applied load moves pitting corrosion initiation at lower concentrations of chlorides. The pitting enhances risk for SCC developing, although the steel is more resistance to HE in comparison with conventional presstressing ste