Reflection on Peer Assisted Learning at PAHS

Peer tutoring is an organized learning experience in which one studentserves as the teacher or tutor, and one is the learner or tutee. Peerteachers and their students share a similar knowledge base and learning experience, which allows the peer-teachers to use language that their learners understand and to explain concepts at an appropriate level. Peerteachers and student-learners also share a similar social context because of their similar social roles, and because of this, student learners feel more at ease with a peer teacher than with a senior clinician. Peer tutoring is a beneficial way for students to learn from each other in the classroom and in small groups, so benefit is not only for the tutee but also to the tutor, predominantly through the development of their own clinical and teaching skills and from the positive feedback obtained by their tutees, thus creating a highly pleasant learning atmosphere and a win-win situation for all.Keywords: peer assisted learning (PAL), PBL, tuto

Land Use and Land Cover Change Detection and Analysis of Indore District

Indore, one of the cities in India's central region, is responsible for the sluggish but steady increase of the country's population and industrialisation. Three decades ago, the city's population and size were minimal. In recent years, however, Indore has assumed charge of the city's economic activity in order to assess the changes and determine the city's future planning. To achieve this objective, remotely sensed Landsat 8 pictures from 2014 and 2022 were used to detect changes. This study included both unsupervised and supervised classification methods, however the accuracy of the supervised classification algorithm is approximately 92.5 percent in 2014 and 90 percent in 2022. This outcome informs the formation of the change detection for what has changed. Keywords: Unsupervised classification, LULC, Indore

Land Use and Land Cover Change Detection and Analysis of Indore District

Indore, one of the cities in India's central region, is responsible for the sluggish but steady increase of the country's population and industrialisation. Three decades ago, the city's population and size were minimal. In recent years, however, Indore has assumed charge of the city's economic activity in order to assess the changes and determine the city's future planning. To achieve this objective, remotely sensed Landsat 8 pictures from 2014 and 2022 were used to detect changes. This study included both unsupervised and supervised classification methods, however the accuracy of the supervised classification algorithm is approximately 92.5 percent in 2014 and 90 percent in 2022. This outcome informs the formation of the change detection for what has changed. Keywords: Unsupervised classification, LULC, Indore

Translation and cultural adaptation of EORTC QLQ-LC 29 into Nepalese language for lung cancer patients in Nepal

Background: The quality of life (QoL) of patients with lung cancer (LC) may be affected by disease-related limitations such as patients’ functioning, the severity of symptoms, financial problems resulting along with the side effects of the treatment. The objective of this study was to translate LC-specific QoL questionnaire EORTC QLQ-LC29 into Nepalese language for Nepalese LC patients. Methods: In the process of translation, the European Organization for Research and Treatment of Cancer (EORTC) translations guidelines were followed. The translated questionnaire was pilot-tested in a sample of 15 patients with LC. Descriptive statistics were calculated with SPSS version 21.0. Results: All steps of the EORTC translation guideline were followed successfully. Fifteen lung cancer patients were included in the pilot study. Sixty percent were male and the mean age was 49.87 (range 21–76 years). For all items not related to thoracic surgery, patients used the entire range of the response options from 1 to 4 and no missing responses were observed. The highest mean (indicating a high symptom burden) was observed for the item number. 35 (shortness of breath; Mean = 3.33, SD = 1.11) and the lowest mean for an item number. 45 (dizzy; Mean = 1.73, SD = 0.96). Conclusion: The Nepalese version of EORTC QLQ-LC29 is a result of a successfully conducted rigorous translation procedure, and is highly comprehensible as well as acceptable to Nepalese LC patients. Thus, the Nepalese version of EORTC QLQ-LC29 is ready to be used in international clinical studies as well as in Nepalese clinical practice

Metabolic signaling directs the reciprocal lineage decisions of αβ and γδ T cells

Wiring metabolic signaling circuits in thymocytes Cell differentiation is often accompanied by metabolic changes. Yang et al. report that generation of double-positive (DP) thymocytes from double-negative (DN) cells coincides with dynamic regulation of glycolytic and oxidative metabolism. Given the central role of mechanistic target of rapamycin complex 1 (mTORC1) signaling in regulating metabolic changes, they examined the role of mTORC1 pathway in thymocyte development by conditionally deleting RAPTOR, the key component of the mTORC1 complex, in thymocytes. Loss of RAPTOR impaired the DN-to-DP transition, but unexpectedly also perturbed the balance between αβ and γδ T cells and promoted the generation of γδ T cells. Their studies highlight an unappreciated role for mTORC1-dependent metabolic changes in controlling thymocyte fates. The interaction between extrinsic factors and intrinsic signal strength governs thymocyte development, but the mechanisms linking them remain elusive. We report that mechanistic target of rapamycin complex 1 (mTORC1) couples microenvironmental cues with metabolic programs to orchestrate the reciprocal development of two fundamentally distinct T cell lineages, the αβ and γδ T cells. Developing thymocytes dynamically engage metabolic programs including glycolysis and oxidative phosphorylation, as well as mTORC1 signaling. Loss of RAPTOR-mediated mTORC1 activity impairs the development of αβ T cells but promotes γδ T cell generation, associated with disrupted metabolic remodeling of oxidative and glycolytic metabolism. Mechanistically, we identify mTORC1-dependent control of reactive oxygen species production as a key metabolic signal in mediating αβ and γδ T cell development, and perturbation of redox homeostasis impinges upon thymocyte fate decisions and mTORC1-associated phenotypes. Furthermore, single-cell RNA sequencing and genetic dissection reveal that mTORC1 links developmental signals from T cell receptors and NOTCH to coordinate metabolic activity and signal strength. Our results establish mTORC1-driven metabolic signaling as a decisive factor for reciprocal αβ and γδ T cell development and provide insight into metabolic control of cell signaling and fate decisions. Development of αβ and γδ T cells requires coupling of environmental signals with metabolic and redox regulation by mTORC1. Development of αβ and γδ T cells requires coupling of environmental signals with metabolic and redox regulation by mTORC1

Retrofitting parallelism onto OCaml.

OCaml is an industrial-strength, multi-paradigm programming language, widely used in industry and academia. OCaml is also one of the few modern managed system programming languages to lack support for shared memory parallel programming. This paper describes the design, a full-fledged implementation and evaluation of a mostly-concurrent garbage collector (GC) for the multicore extension of the OCaml programming language. Given that we propose to add parallelism to a widely used programming language with millions of lines of existing code, we face the challenge of maintaining backwards compatibility--not just in terms of the language features but also the performance of single-threaded code running with the new GC. To this end, the paper presents a series of novel techniques and demonstrates that the new GC strikes a balance between performance and feature backwards compatibility for sequential programs and scales admirably on modern multicore processors

Novel Inhibitor Design for Hemagglutinin against H1N1 Influenza Virus by Core Hopping Method

The worldwide spread of H1N1 avian influenza and the increasing reports about its resistance to the current drugs have made a high priority for developing new anti-influenza drugs. Owing to its unique function in assisting viruses to bind the cellular surface, a key step for them to subsequently penetrate into the infected cell, hemagglutinin (HA) has become one of the main targets for drug design against influenza virus. To develop potent HA inhibitors, the ZINC fragment database was searched for finding the optimal compound with the core hopping technique. As a result, the Neo6 compound was obtained. It has been shown through the subsequent molecular docking studies and molecular dynamic simulations that Neo6 not only assumes more favorable conformation at the binding pocket of HA but also has stronger binding interaction with its receptor. Accordingly, Neo6 may become a promising candidate for developing new and more powerful drugs for treating influenza. Or at the very least, the findings reported here may provide useful insights to stimulate new strategy in this area

Who should be prioritized for renal transplantation?: Analysis of key stakeholder preferences using discrete choice experiments

Background Policies for allocating deceased donor kidneys have recently shifted from allocation based on Human Leucocyte Antigen (HLA) tissue matching in the UK and USA. Newer allocation algorithms incorporate waiting time as a primary factor, and in the UK, young adults are also favoured. However, there is little contemporary UK research on the views of stakeholders in the transplant process to inform future allocation policy. This research project aimed to address this issue. Methods Discrete Choice Experiment (DCE) questionnaires were used to establish priorities for kidney transplantation among different stakeholder groups in the UK. Questionnaires were targeted at patients, carers, donors / relatives of deceased donors, and healthcare professionals. Attributes considered included: waiting time; donor-recipient HLA match; whether a recipient had dependents; diseases affecting life expectancy; and diseases affecting quality of life. Results Responses were obtained from 908 patients (including 98 ethnic minorities); 41 carers; 48 donors / relatives of deceased donors; and 113 healthcare professionals. The patient group demonstrated statistically different preferences for every attribute (i.e. significantly different from zero) so implying that changes in given attributes affected preferences, except when prioritizing those with no rather than moderate diseases affecting quality of life. The attributes valued highly related to waiting time, tissue match, prioritizing those with dependents, and prioritizing those with moderate rather than severe diseases affecting life expectancy. Some preferences differed between healthcare professionals and patients, and ethnic minority and non-ethnic minority patients. Only non-ethnic minority patients and healthcare professionals clearly prioritized those with better tissue matches. Conclusions Our econometric results are broadly supportive of the 2006 shift in UK transplant policy which emphasized prioritizing the young and long waiters. However, our findings suggest the need for a further review in the light of observed differences in preferences amongst ethnic minorities, and also because those with dependents may be a further priority.</p

Piperidinols that show anti-tubercular activity as inhibitors of arylamine N-acetyltransferase: an essential enzyme for mycobacterial survival inside macrophages

Latent M. tuberculosis infection presents one of the major obstacles in the global eradication of tuberculosis (TB). Cholesterol plays a critical role in the persistence of M. tuberculosis within the macrophage during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into cell-wall lipids. Arylamine N-acetyltransferase (NAT) is encoded within a gene cluster that is involved in the cholesterol sterol-ring degradation and is essential for intracellular survival. The ability of the NAT from M. tuberculosis (TBNAT) to utilise propionyl-CoA links it to the cholesterol-catabolism pathway. Deleting the nat gene or inhibiting the NAT enzyme prevents intracellular survival and results in depletion of cell-wall lipids. TBNAT has been investigated as a potential target for TB therapies. From a previous high-throughput screen, 3-benzoyl-4-phenyl-1-methylpiperidinol was identified as a selective inhibitor of prokaryotic NAT that exhibited antimycobacterial activity. The compound resulted in time-dependent irreversible inhibition of the NAT activity when tested against NAT from M. marinum (MMNAT). To further evaluate the antimycobacterial activity and the NAT inhibition of this compound, four piperidinol analogues were tested. All five compounds exert potent antimycobacterial activity against M. tuberculosis with MIC values of 2.3-16.9 µM. Treatment of the MMNAT enzyme with this set of inhibitors resulted in an irreversible time-dependent inhibition of NAT activity. Here we investigate the mechanism of NAT inhibition by studying protein-ligand interactions using mass spectrometry in combination with enzyme analysis and structure determination. We propose a covalent mechanism of NAT inhibition that involves the formation of a reactive intermediate and selective cysteine residue modification. These piperidinols present a unique class of antimycobacterial compounds that have a novel mode of action different from known anti-tubercular drugs

Ethanol-Mediated Regulation of Cytochrome P450 2A6 Expression in Monocytes: Role of Oxidative Stress-Mediated PKC/MEK/Nrf2 Pathway

Cytochrome P450 2A6 (CYP2A6) is known to metabolize nicotine, the major constituent of tobacco, leading to the production of toxic metabolites and induction of oxidative stress that result in liver damage and lung cancer. Recently, we have shown that CYP2A6 is induced by ethanol and metabolizes nicotine into cotinine and other metabolites leading to generation of reactive oxygen species (ROS) in U937 monocytes. However, the mechanism by which CYP2A6 is induced by ethanol is unknown. In this study, we have examined the role of the PKC/Nrf2 pathway (protein kinase C-mediated phosphorylation and translocation of nuclear erythroid 2-related factor 2 to the nucleus) in ethanol-mediated CYP2A6 induction. Our results showed that 100 mM ethanol significantly induced CYP2A6 mRNA and protein (∼150%) and increased ROS formation, and induction of gene expression and ROS were both completely blocked by treatment with either a CYP2E1 inhibitor (diallyl sulfide) or an antioxidant (vitamin C). The results suggest the role of oxidative stress in the regulation of CYP2A6 expression. Subsequently, we investigated the role of Nrf2 pathway in oxidative stress-mediated regulation of CYP2A6 expression in U937 monocytes. Our results showed that butylated hydroxyanisole, a stabilizer of nuclear Nrf2, increased CYP2A6 levels >200%. Staurosporine, an inhibitor of PKC, completely abolished ethanol-induced CYP2A6 expression. Furthermore, our results showed that a specific inhibitor of mitogen-activated protein kinase kinase (MEK) (U0126) completely abolished ethanol-mediated CYP2A6 induction and Nrf2 translocation. Overall, these results suggest that CYP2E1-mediated oxidative stress produced as a result of ethanol metabolism translocates Nrf2 into the nucleus through PKC/MEK pathway, resulting in the induction of CYP2A6 in monocytes. An increased level of CYP2A6 in monocytes is expected to further increase oxidative stress in smokers through CYP2A6-mediated nicotine metabolism. Thus, this study has clinical relevance because of the high incidence of alcohol use among smokers, especially in HIV-infected individuals