The formation of supermassive black holes in the first galaxies

We discuss the formation of supermassive black holes in the early universe, and how to probe their subsequent evolution with the upcoming mm/sub-mm telescope ALMA. We first focus on the chemical and radiative conditions for black hole formation, in particular considering radiation trapping and molecular dissociation effects. We then turn our attention towards the magnetic properties in the halos where the first black holes form, and show that the presence of turbulence may lead to a magnetic dynamo, which could support the black hole formation process by providing an efficient means of transporting the angular momentum. We finally focus on observable properties of high-redshift black holes with respect to ALMA, and discuss how to distinguish between chemistry driven by the starburst and chemistry driven by X-rays from the black hole.Comment: Contribution to AIP conference proceedings "First Stars and Galaxies: Challenges in the Next Decade". 4 pages, 3 figure

In silico and in vitro validation of some benzimidazole derivatives as adenosine deaminase inhibitors

1175-1182Benzimidazole nucleus considered as an important scaffold for developing drug candidates against a wide spectrum of diseases. Adenosine deaminase (ADA), an enzyme present in purine metabolic pathway, has a significant role in inflammatory and malignant diseases and hence it is considered as a major target for drug development. The present study investigates ADA inhibitory potential of selected benzimidazole derivatives by using in silico and in vitro methods. Molecular docking and dynamics simulations have been carried out to identify potential ADA activesite binders from benzimidazole derivatives. Compounds having strong binding affinities were selected for enzyme inhibition assays and fluorescent binding studies. The results showed that the pyridinyl and butyl derivatives of benzimidazole possess significant ADA inhibitory potential.The study proposes these compounds can be used as potent candidates for developing ADA inhibitor drugs

In silico and in vitro validation of some benzimidazole derivatives as adenosine deaminase inhibitors

Benzimidazole nucleus considered as an important scaffold for developing drug candidates against a wide spectrum of diseases. Adenosine deaminase (ADA), an enzyme present in purine metabolic pathway, has a significant role in inflammatory and malignant diseases and hence it is considered as a major target for drug development. The present study investigates ADA inhibitory potential of selected benzimidazole derivatives by using in silico and in vitro methods. Molecular docking and dynamics simulations have been carried out to identify potential ADA activesite binders from benzimidazole derivatives. Compounds having strong binding affinities were selected for enzyme inhibition assays and fluorescent binding studies. The results showed that the pyridinyl and butyl derivatives of benzimidazole possess significant ADA inhibitory potential.The study proposes these compounds can be used as potent candidates for developing ADA inhibitor drugs

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

An improved Evaporation Rate-Water Cycle Algorithm based Genetic Algorithm for solving generalized ratio problems

This paper presents an efficient metaheuristic approach for optimizing the generalized ratio problems such as the sum and multiplicative of linear or nonlinear ratio objective function with affine constraints. This paper focuses on the significance of hybrid techniques, which are implemented by using GA and ER-WCA to increase efficiency and robustness for solving linear and nonlinear generalized ratio problems. Initially, GA starts with an initial random population and it is processed by genetic operators. ER-WCA will observe and preserve the GAs fittest chromosome in each cycle and every generation. This Genetic ER-WCA algorithm is provided with better optimal solutions while solving constrained ratio optimization problems. Also, the effectiveness of the proposed genetic ER-WCA algorithm is analyzed while solving the large scale ratio problems. The results and performance of the proposed algorithm ensures a strong optimization and improves the exploitative process when compared to the other existing metaheuristic techniques. Numerical problems and applications are used to test the performance of the convergence and the accuracy of the approached method. The behavior of this Genetic ER-WCA algorithm is compared with those of evolutionary algorithms namely Neural Network Algorithm, Grey Wolf Optimization, Evaporation Rate - Water Cycle Algorithm, Water Cycle Algorithm, Firefly algorithm, Cuckoo search algorithm. The evaluated results show that the proposed algorithm increases the convergence and accuracy more than other existing algorithms

Approaching global education development with a decolonial lens:teachers’ reflections

Abstract In this paper, we as the teachers and researchers of a course titled Global education development informed by theories of decoloniality, report on our analysis of our self-critical and constructive dialogue on the course design, its underlying assumptions, expectations, implementation, success and needs for improvement. We centered decoloniality from the beginning of the course, problematised binary-thinking and encouraged our students to look at issues within the field of development and education in pluriversal ways. Our gestures toward decolonial pedagogy in the course were complicated by our own entanglements with coloniality as well as structural factors such as the context of Finland, where the colonial past is seldom addressed. Despite these contradictions and challenges, we aspire to continue thinking through decoloniality to decenter the dominant liberal frameworks within global education development

Physiological Screening of Green Gram (Vigna radiata L.) Varieties by Seedling Germination Traits under Salinity Stress

Among the legumes, pulses are the most important component in India as they have very high protein resources. Green gram (Vigna radiata) is the most essential one when compared to other pulses regarding high nutritional value, enriching soil fertility and being a short duration crop. In India, pulses cultivation faces salinity stress which is a most constraint factor on its production. Hence, an experiment was performed with the purpose of analyzing morpho- physiological differences in high difference green gram varieties, which are MH 421,VBN 2,VBN 4,CO 8 and CO(Gg) 912 under salinity stress condition. This experiment was done at laboratory condition under various concentration level of Sodium Chloride (NaCl). These levels create different levels of salinity stress, the above five green gram varieties where screened for identifying their salinity stress and the important parameters which include radicle length, shoot length, plant height, germination percentage and seed Vigor were recorded

<em>In vitro</em> Assessment of Selected Benzoic Acid Derivatives as Anti-Inflammatory Compounds

330-336Inflammation is a major reason of pathophysiology of several diseases, causing a number of disarrays. The present research involved exploring inhibition of soybean 5-lipoxygenase (5-LOX) by various benzoic acid derivatives (eudesmic acid, veratric acid, cumic acid, and syringic acid) and their kinetics studies, comparing with vanillin as a standard reference. Isothermal titration calorimetry (ITC) was performed to determine kinetics of the biomolecular interactions. Further, molecular docking studies were performed using GLIDE module of Schrodinger software to determine the inter-molecular interactions between the ligand and the target. Result underlined that four of the investigated derivatives exhibited potent inhibition of 5-LOX in a competitive manner with IC50 values <60 µM. ITC study demonstrated that all derivatives bind effectively with a single domain of the target. Molecular docking studies revealed that all the four candidates displayed good interaction with the target. As found from Glide scores, veratric acid interacted stronger than other derivatives (GLIDE Score of -10.72 kcal/mol), forming two hydrogen bonds with residues GLN514 and GLN716, quite similar to the standard reference. ITC and GLIDE score analyses showed difference in the binding strength of the derivatives. This study would help in developing novel inhibitors, anti-inflammation as well as understanding mechanism(s) of ligand-enzyme interaction

A clinical study on musculoskeletal changes seen in type 2 diabetes mellitus: A single-center study

Background: Type 2 Diabetes mellitus (T2DM) may affect the musculoskeletal (MSK) system in a variety of ways. The impacts can be debilitating enough to impair functional ability and quality of life. MSK complications are the most common endocrine arthropathies which are often under-recognized and poorly treated. This study was done to evaluate the prevalence of MSK complications and its correlation with microvascular complications of T2DM given the paucity of similar studies in India particularly South India. Materials and Methods: A cross-sectional study was conducted on 130 diabetic patients at a tertiary care hospital in Bengaluru. The patient's demographic details, clinical profile including history, general physical examination, systemic examination, and relevant investigations were done to record microvascular complications. A thorough MSK system examination along with imaging of bones and joints was also performed. Results: Out of 130 diabetic patients, 21 patients (16.2%) had MSK complications of which 47.6% (n = 10) of them had carpal tunnel syndrome and 42.8% (n = 9) had frozen shoulder and 9.5% (n = 2) had diabetic amyotrophy. It was also noted that patients who were on oral hypoglycemic agents alone were more likely to develop MSK complications (57.14%) than patients solely on insulin (14.2%). Poor glycemic control, existing microvascular complications, and low high-density lipoprotein were found to be associated with increased risk of MSK complications. Conclusion: The prevalence of MSK complications in T2DM patients is quite significant and is also associated with microvascular complications. Improved glycemic control in T2DM was found to reduce the burden of such complications. Early identification of MSK complications can improve the quality of life in diabetic patients and hence demands proper screening and follow-up

Designing of enzyme inhibitors based on active site specificity: lessons from methyl gallate and its lipoxygenase inhibitory profile

<p>Methyl gallate was purified, by lipoxygenase (LOX) inhibitory activity-guided method since its alleged anti-inflammatory property, from <i>Bergenia ligulata</i> (Wall), a plant used in the traditional, Ayurvedic system of medicine extensively. The LOX inhibitory property of methyl gallate was studied by enzyme kinetics, isothermal titration calorimetry and molecular docking followed by molecular simulation studies. The wet-laboratory experiments and <i>in silico</i> studies showed complete agreement, and promise of methyl gallate as a drug-lead molecular scaffold for anti-inflammatory therapy, based on LOX inhibition. The expressed work shows the need of nonactive site binding parameters to be considered while designing of inhibitors based on the specificities toward active sites of enzymes.</p