K30, H150, and H168 Are Essential Residues for Coordinating Pyridoxal 5′-Phosphate of O-Acetylserine Sulfhydrylase from Acidithiobacillus ferrooxidans

O-acetylserine sulfhydrylase (OASS) is a key enzyme involved in the pathway of the cysteine biosynthesis. The gene of OASS from Acidithiobacillus ferrooxidans ATCC 23270 was cloned and expressed in E. coli, the soluble protein was purified by one-step affinity chromatography to apparent homogeneity. Colors and UV–vis scanning results of the recombinant protein confirmed that it was a pyridoxal 5′-phosphate (PLP)-containing protein. Sequence alignment and site-directed mutation of the enzyme revealed that the cofactor PLP is covalently bound in Schiff base linkage with K30, as well as the two residues H150 and H168 were the crucial residues for PLP binding and stabilization

Dimethyl sulfoxide blocks herpes simplex virus-1 productive infection in vitro acting at different stages with positive cooperativity. Application of micro-array analysis

BACKGROUND: Dimethyl sulfoxide (DMSO) is frequently used at a concentration of up to 95% in the formulation of antiherpetic agents because of its properties as a skin penetration enhancer. Here, we have analyzed the effect of DMSO on several parameters of Herpes Simplex Virus replication. METHODS: Productive infection levels of HSV-1 were determined by plaque assay or by reporter gene activity, and its DNA replication was estimated by PCR. Transcript levels were evaluated with HSV-specific DNA micro-arrays. RESULTS: DMSO blocks productive infection in vitro in different cell types with a 50% inhibitory concentration (IC(50)) from 0.7 to 2% depending upon the multiplicity of infection. The concentration dependence exhibits a Hill coefficient greater than 1, indicating that DMSO blocks productive infection by acting at multiple different points (mechanisms of action) with positive cooperativity. Consistently, we identified at least three distinct temporal target mechanisms for inhibition of virus growth by DMSO. At late stages of infection, DMSO reduces virion infectivity, and markedly inhibits viral DNA replication. A third mode of action was revealed using an oligonucleotide-based DNA microarray system for HSV. These experiments showed that DMSO reduced the transcript levels of many HSV-1 genes; including several genes coding for proteins involved in forming and assembling the virion. Also, DMSO markedly inhibited some but not all early transcripts indicating a previously unknown mode for inhibiting the early phase of HSV transcription-replication cycle. CONCLUSION: These observations suggest that DMSO itself may have a role in the anti-herpetic activity of formulations utilizing it as a dispersant

Women's Experiences and Views about Costs of Seeking Malaria Chemoprevention and other Antenatal Services: A Qualitative Study from two Districts in Rural Tanzania.

The Tanzanian government recommends women who attend antenatal care (ANC) clinics to accept receiving intermittent preventive treatment against malaria during pregnancy (IPTp) and vouchers for insecticide-treated nets (ITNs) at subsidized prices. Little emphasis has been paid to investigate the ability of pregnant women to access and effectively utilize these services. To describe the experience and perceptions of pregnant women about costs and cost barriers for accessing ANC services with emphasis on IPTp in rural Tanzania. Qualitative data were collected in the districts of Mufindi in Iringa Region and Mkuranga in Coast Region through 1) focus group discussions (FGDs) with pregnant women and mothers to infants and 2) exit-interviews with pregnant women identified at ANC clinics. Data were analyzed manually using qualitative content analysis methodology. FGD participants and interview respondents identified the following key limiting factors for women's use of ANC services: 1) costs in terms of money and time associated with accessing ANC clinics, 2) the presence of more or less official user-fees for some services within the ANC package, and 3) service providers' application of fines, penalties and blame when failing to adhere to service schedules. Interestingly, the time associated with travelling long distances to ANC clinics and ITN retailers and with waiting for services at clinic-level was a major factor of discouragement in the health seeking behaviour of pregnant women because it seriously affected their domestic responsibilities. A variety of resource-related factors were shown to affect the health seeking behaviour of pregnant women in rural Tanzania. Thus, accessibility to ANC services was hampered by direct and indirect costs, travel distances and waiting time. Strengthening of user-fee exemption practices and bringing services closer to the users, for example by promoting community-directed control of selected public health services, including IPTp, are urgently needed measures for increasing equity in health services in Tanzania

Combining Deep Facial and Ambient Features for First Impression Estimation

14th European Conference on Computer Vision (ECCV) -- OCT 08-16, 2016 -- Amsterdam, NETHERLANDSFirst impressions influence the behavior of people towards a newly encountered person or a human-like agent. Apart from the physical characteristics of the encountered face, the emotional expressions displayed on it, as well as ambient information affect these impressions. In this work, we propose an approach to predict the first impressions people will have for a given video depicting a face within a context. We employ pre-trained Deep Convolutional Neural Networks to extract facial expressions, as well as ambient information. After video modeling, visual features that represent facial expression and scene are combined and fed to a Kernel Extreme Learning Machine regressor. The proposed system is evaluated on the ChaLearn Challenge Dataset on First Impression Recognition, where the classification target is the Big Five personality trait labels for each video. Our system achieved an accuracy of 90.94% on the sequestered test set, 0.36% points below the top system in the competition

The Surgical Infection Society revised guidelines on the management of intra-abdominal infection

Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations. Methods: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council. Results: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included. Summary: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline

Modelling human performance within manufacturing systems design:from a theoretical towards a practical framework

Computer-based simulation is frequently used to evaluate the capabilities of proposed manufacturing system designs. Unfortunately, the real systems are often found to perform quite differently from simulation predictions and one possible reason for this is an over-simplistic representation of workers' behaviour within current simulation techniques. The accuracy of design predictions could be improved through a modelling tool that integrates with computer-based simulation and incorporates the factors and relationships that determine workers' performance. This paper explores the viability of developing a similar tool based on our previously published theoretical modelling framework. It focuses on evolving this purely theoretical framework towards a practical modelling tool that can actually be used to expand the capabilities of current simulation techniques. Based on an industrial study, the paper investigates how the theoretical framework works in practice, analyses strengths and weaknesses in its formulation, and proposes developments that can contribute towards enabling human performance modelling in a practical way

Effect of Recombinant Cytokines on the Expression of Natural Killer Cell Receptors from Patients with TB or/and HIV Infection

BACKGROUND: NK cells express several specialized receptors through which they recognize and discriminate virally-infected/tumor cells efficiently from healthy cells and kill them. This ability to lyse is regulated by an array of inhibitory or activating receptors. The present study investigated the frequency of various NK receptors expressed by NK cell subsets from HIV-infected TB patients. The effect of IL-15+IL-12 stimulation on the expression of NK receptors was also studied. METHODOLOGY/PRINCIPAL FINDINGS: The study included 15 individuals each from normal healthy subjects, pulmonary tuberculosis patients, HIV-infected individuals and patients with HIV and tuberculosis co-infection. The expression of NK cell receptors was analyzed on two NK cell subsets within the peripheral blood: CD16+CD3- and CD56+CD3- using flow cytometry. The expression of inhibitory receptors (CD158a, CD158b, KIRp70, CD85j and NKG2A) on NK subsets was increased in HIV, when compared to NHS. But the response in HIV-TB was not uniform. Stimulation with IL-15+IL-12 dropped (p<0.05) the expression of CD85j and NKG2A in HIV. The basal expression of natural cytotoxicity receptors (NKp30 and NKp46) on NK cell subsets was lowered (p<0.05) in HIV and HIV-TB as compared to NHS. However, the expression of NKp44 and NKG2D was elevated in HIV. Enhanced NKp46 and NKG2D expression was observed in HIV with IL-15+IL-12 stimulation. The coreceptor NKp80 was found to be expressed in higher numbers on NK subsets from HIV compared to NHS, which elevated with IL-15+IL-12 stimulation. The expression of NK receptors and response to stimulation was primarily on CD56+CD3- subset. CONCLUSIONS/SIGNIFICANCE: IL-15+IL-12 has an immunomodulatory effect on NK cell subsets from HIV-infected individuals viz down-regulation of iNKRs, elevation of activatory receptors NKp46 and NKG2D, and induction of coreceptor NKp80. IL-15+IL-12 is not likely to be of value when co-infected with TB probably due to the influence of tuberculosis

Acute Beneficial Hemodynamic Effects of a Novel 3D-Echocardiographic Optimization Protocol in Cardiac Resynchronization Therapy

Post-implantation therapies to optimize cardiac resynchronization therapy (CRT) focus on adjustments of the atrio-ventricular (AV) delay and ventricular-to-ventricular (VV) interval. However, there is little consensus on how to achieve best resynchronization with these parameters. The aim of this study was to examine a novel combination of doppler echocardiography (DE) and three-dimensional echocardiography (3DE) for individualized optimization of device based AV delays and VV intervals compared to empiric programming.25 recipients of CRT (male: 56%, mean age: 67 years) were included in this study. Ejection fraction (EF), the primary outcome parameter, and left ventricular (LV) dimensions were evaluated by 3DE before CRT (baseline), after AV delay optimization while pacing the ventricles simultaneously (empiric VV interval programming) and after individualized VV interval optimization. For AV delay optimization aortic velocity time integral (AoVTI) was examined in eight different AV delays, and the AV delay with the highest AoVTI was programmed. For individualized VV interval optimization 3DE full-volume datasets of the left ventricle were obtained and analyzed to derive a systolic dyssynchrony index (SDI), calculated from the dispersion of time to minimal regional volume for all 16 LV segments. Consecutively, SDI was evaluated in six different VV intervals (including LV or right ventricular preactivation), and the VV interval with the lowest SDI was programmed (individualized optimization).EF increased from baseline 23±7% to 30±8 (p<0.001) after AV delay optimization and to 32±8% (p<0.05) after individualized optimization with an associated decrease of end-systolic volume from a baseline of 138±60 ml to 115±42 ml (p<0.001). Moreover, individualized optimization significantly reduced SDI from a baseline of 14.3±5.5% to 6.1±2.6% (p<0.001).Compared with empiric programming of biventricular pacemakers, individualized echocardiographic optimization with the integration of 3-dimensional indices into the optimization protocol acutely improved LV systolic function and decreased ESV and can be used to select the optimal AV delay and VV interval in CRT