Design, synthesis, characterization and in vitro evaluation of some novel thiol-substituted 1,3,4-oxadiazoles as GlmS inhibitors

The development of novel medications with previously unidentified action mechanisms is required due to the increasing in antibiotic resistance amongst dangerous microbes. The major goal of the research was to develop in silico and in vitro antibacterial methods for designing an active thiol substituted oxadiazole inhibitor targeting gram-negative and gram-positive bacteria's GlmS receptor. 1,3,4-Oxadiazole was proposed as a scaffold, and the possibility of its synthesis was examined. The least amount of free energy in the ligand configurations was chosen. Analyses of the novel molecules' characteristics were done using ADMET studies. There were four distinct reactions used in the synthesis processes. As the first reagent, substituted carboxylic acids were utilized. Synthesized compounds were characterized by spectral studies and minimum inhibitory concentration was evaluated by in vitro antibacterial examinations of synthesized compounds. Ciprofloxacin served as the study's reference drug. Based on in vitro studies and in silico molecular docking, ROS1-4 established strong binding energy, while ROS3 revealed significant antibacterial activity. These findings support the hypothesis that the proposed scaffold significantly inhibits the GlmS receptor protein

Bianchi Type I Cosmology in Generalized Saez-Ballester Theory via Noether Gauge Symmetry

In this paper, we investigate the generalized Saez-Ballester scalar-tensor theory of gravity via Noether gauge symmetry (NGS) in the background of Bianchi type I cosmological spacetime. We start with the Lagrangian of our model and calculate its gauge symmetries and corresponding invariant quantities. We obtain the potential function for the scalar field in the exponential form. For all the symmetries obtained, we determine the gauge functions corresponding to each gauge symmmetry which include constant and dynamic gauge. We discuss cosmological implications of our model and show that it is compatible with the observational data.Comment: 13 pages, 2 figures, accepted for publication in 'European Physical Journal C

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Reassessing climate classification for buildings under climate change: Indian context

Climate classification is essential for buildings because it influences the planning and design of a building, its orientation, building geometry and design of building envelopes such as walls, roofs and openings. In the event of climate change, the existing classifications must be revised or updated to provide both proper guidelines for the design and construction of buildings and adaptation strategies for the existing buildings. The study attempted a comprehensive review of the existing global and Indian classification of climates on buildings. The paper analysed the existing Indian climate classification to include the climate change scenarios by studying 310 locations. The warming trend observed in the locations establishes a need for revision in classification

An updated review on factors and their inter-linked influences on photovoltaic system performance

Globally installed solar photovoltaics (PV) capacity has crossed three hundred gigawatts and is increasing each year. As the share of solar PV in the energy mix of a country increases, forecasting PV power available will be crucial. To forecast the instantaneous and long-term PV power output, understanding the factors influencing them is necessary. In this view, this work elaborates on the factors that impact the PV system through tabulation and graphical explanation. Further, a discussion of the articles related to the dust-induced change in performance is made. To understand the impact of dust on solar PV systems in depth, advanced instrumentation and methodologies have been used in the past few years. One of the methods is the measurement of spectral transmittance/reflectance/absorptance of the dust layer on the PV panel. This has led to the question whether a thin layer of some specific dust can be beneficial by absorbing infrared (IR) heat and hence allowing the PV cells to operate at a lower temperature. Many controlled experiments in the laboratory have been made using the artificial dust and sun simulators; and such studies aid in the development of numerical models. Research in modeling, mathematical analysis (from first principles) of dust deposition, and calculation of its impact on panels have been given importance in recent years. Outdoor experiments are relatively more common than other modes of research in this field. Studies involving the interaction of deposited dust with spectral radiation, improving the correlation between artificial and natural dust deposition, the interplay between dust and atmospheric parameters are to be encouraged

Comparison of performance of solar photovoltaics on dual axis tracker with fixed axis at 13 degrees N latitude

Tracking systems, that continually orient photovoltaic (PV) panels towards the Sun, are expected to increase the power output from the PV panels. Tremendous amount of research is being done and funds are being spent in order to increase the efficiency of PV cells to generate more power. We report the performance of two almost identical PV systems; one at a fixed latitude tilt and the other on a two-axis tracker. We observed that the fixed axis PV panels generated 336.3 kWh, and the dual-axis Sun-tracked PV panels generated 407.2 kWh during August 2012 March 2013. The tracked panels generated 21.2% more electricity than the optimum tilt angle fixed-axis panels. The cost payback calculations indicate that the additional cost of the tracker can be recovered in 450 days

Design, synthesis, characterization and in vitro evaluation of some novel thiol-substituted 1,3,4-oxadiazoles as GlmS inhibitors

148-155The development of novel medications with previously unidentified action mechanisms is required due to the increasing in antibiotic resistance amongst dangerous microbes. The major goal of the research was to develop in silico and in vitro antibacterial methods for designing an active thiol substituted oxadiazole inhibitor targeting gram-negative and grampositive bacteria's GlmS receptor. 1,3,4-Oxadiazole was proposed as a scaffold, and the possibility of its synthesis was examined. The least amount of free energy in the ligand configurations was chosen. Analyses of the novel molecules' characteristics were done using ADMET studies. There were four distinct reactions used in the synthesis processes. As the first reagent, substituted carboxylic acids were utilized. Synthesized compounds were characterized by spectral studies and minimum inhibitory concentration was evaluated by in vitro antibacterial examinations of synthesized compounds. Ciprofloxacin served as the study's reference drug. Based on in vitro studies and in silico molecular docking, ROS1-4 established strong binding energy, while ROS3 revealed significant antibacterial activity. These findings support the hypothesis that the proposed scaffold significantly inhibits the GlmS receptor protein

Deformation processing of an aluminum alloy containing particles: studies on AI-5 pct Si alloy 4043

Al-5 wt pct Si alloy is processed by upset forging in the temperature range 300 K to 800 K and in the strain rate range 0.02 to 200 s−1. The hardness and tensile properties of the product have been studied. A "safe" window in the strain rate-temperature field has been identified for processing of this alloy to obtain maximum tensile ductility in the product. For the above strain rate range, the temperature range of processing is 550 K to 700 K for obtaining high ductility in the product. On the basis of microstructure and the ductility of the product, the temperature-strain rate regimes of damage due to cavity formation at particles and wedge cracking have been isolated for this alloy. The tensile fracture features recorded on the product specimens are in conformity with the above damage mechanisms. A high temperature treatment above ≈600 K followed by fairly fast cooling gives solid solution strengthening in the alloy at room temperature

Correlation of gingival thickness with gingival width, probing depth, and papillary fill in maxillary anterior teeth in students of a dental college in Navi Mumbai

Context: The gingival biotype is of utmost importance for esthetics and biologic function. Anatomical characteristic of periodontium such as gingival thickness (GT), width of keratinized gingiva, and alveolar bone morphology will determine the behavior of periodontium when subjected to physical, chemical, or bacterial insult or during therapeutic procedure. Aims: The aim of this study was to correlate the GT with gingival width (GW), probing depth (PD), and papillary fill (PF) in relation to maxillary anterior region. Settings and Design: Undergraduate dental students and interns from a dental college in Navi Mumbai were enrolled in the study according to the inclusion criteria. Six teeth per subject were assessed; a total of 2178 maxillary anterior teeth were examined. Subjects and Methods: Subjects were examined clinically for GT, width of keratinized gingiva, pocket depth, and interdental PF. The data obtained was tabulated and subjected to statistical analysis. Statistical Analysis Used: Spearman's correlation analysis test was performed to find the correlation of GT with GW, PD, and PF. Results: Positive correlation was found between GT and GW (r = 0.241). No significant correlation could be found between GT and PD; and between GT and PF. Conclusions: The present study confirmed a positive correlation between GT and GW. A weak negative correlation was found between GT and PD