A systematic first-principles investigation of the structural, electronic, mechanical, optical, and thermodynamic properties of Half-Heusler ANiX (ASc, Ti, Y, Zr, Hf; XBi, Sn) for spintronics and optoelectronics applications.

This paper is the first to look at the structural, electronic, mechanical, optical, and thermodynamic properties of the ANiX (ASc, Ti, Y, Zr, Hf; XBi, Sn) half-Heusler (HH) using DFT based first principles method. The lattice parameters that we have calculated are very similar to those obtained in prior investigations with theoretical and experimental data. The positive phonon dispersion curve confirm the dynamical stability of ANiX (ASc, Ti, Y, Zr, Hf; XBi, Sn). The electronic band structure and DOS confirmed that the studied materials ANiX (ASc, Ti, Y, Zr, Hf; XBi, Sn) are direct band gap semiconductors. The investigation also determined significant constants, including dielectric function, absorption, conductivity, reflectivity, refractive index, and loss function. These optical observations unveiled our compounds potential utilization in various electronic and optoelectronic device applications. The elastic constants were used to fulfill the Born criteria, confirming the mechanical stability and ductility of the solids ANiX (ASc, Ti, Y, Zr, Hf; XBi, Sn). The calculated elastic modulus revealed that our studied compounds are elastically anisotropic. Moreover, ANiX (ASc, Ti, Y, Zr, Hf; XBi, Sn) has a very low minimum thermal conductivity (Kmin), and a low Debye temperature (θD), which indicating their appropriateness for utilization in thermal barrier coating (TBC) applications. The Helmholtz free energy (F), internal energy (E), entropy (S), and specific heat capacity (Cv) are determined by calculations derived from the phonon density of states.

Load frequency stabilization of distinct hybrid conventional and renewable power systems incorporated with electrical vehicles and capacitive energy storage.

Maintaining a power balance between generation and demand is generally acknowledged as being essential to maintaining a system frequency within reasonable bounds. This is especially important for linked renewable-based hybrid power systems (HPS), where disruptions are more likely to occur. This paper suggests a prominent modified "Fractional order-proportional-integral with double derivative (FOPIDD2) controller" as an innovative HPS controller in order to navigate these obstacles. The recommended control approach has been validated in power systems including wind, reheat thermal, solar, and hydro generating, as well as capacitive energy storage and electric vehicle. The improved controller's performance is evaluated by comparing it to regular FOPID, PID, and PIDD2 controllers. Furthermore, the gains of the newly structured FOPIDD2 controller are optimized using a newly intended algorithm terms as squid game optimizer (SGO). The controller's performance is compared to benchmarks such as the grey wolf optimizer (GWO) and jellyfish search optimization. By comparing performance characteristics such as maximum frequency undershoot/overshoot, and steadying time, the SGO-FOPIDD2 controller outperforms the other techniques. The suggested SGO optimized FOPIDD2 controller was analyzed and validated for its ability to withstand the influence of power system parameter uncertainties under various loading scenarios and situations. Without any complicated design, the results show that the new controller can work steadily and regulate frequency with an appropriate controller coefficient.

Frequency regulation of interconnected hybrid power system with Assimilation of electrical vehicles.

Recent widespread connections of renewable energy resource (RESs) in place of fossil fuel supplies and the adoption of electrical vehicles in place of gasoline-powered vehicles have given birth to a number of new concerns. The control architecture of linked power networks now faces an increasingly pressing challenge: tie-line power fluctuations and reducing frequency deviations. Because of their nature and dependence on external circumstances, RESs are analogous to continually fluctuating power generators. Using a fractional order-based frequency regulator, this work presents a new method for improving the frequency regulation in a two-area interconnected power system. In order to deal with the frequency regulation difficulties of the hybrid system integrated with RES, the suggested controller utilizes the modified form of fractional order proportional integral derivative (FOPID) controller known as FOI-PDN controller. The new proposed controllers are designed using the white shark optimizer (WSO), a current powerful bioinspired meta heuristic algorithm which has been motivated by the learning abilities of white sharks when actively hunting in the environment. The suggested FOI-PDN controller's performance was compared to that of various control methodologies such as FOPID, and PID. Furthermore, the WSO findings are compared to those of other techniques such as the salp swarm algorithm, sine cosine algorithm and fitness dependent optimizer. The recommended controller and design approach have been tested and validated at different loading conditions and different circumstances, as well as their robustness against system parameter suspicions. The simulation outcomes demonstrate that the WSO-based tuned FOI-PDN controller successfully reduces peak overshoot by 73.33%, 91.03%, and 77.21% for region-2, region-1, and link power variation respectively, and delivers minimum undershoot of 89.12%, 83.11%, and 78.10% for both regions and tie-line. The obtained findings demonstrate the new proposed controller's stable function and frequency controlling performance with optimal controller parameters and without the requirement for a sophisticated design process.

Stabilization and tracking control of underactuated ball and beam system using metaheuristic optimization based TID-F and PIDD2-PI control schemes.

In this paper, we propose two different control strategies for the position control of the ball of the ball and beam system (BBS). The first control strategy uses the proportional integral derivative-second derivative with a proportional integrator PIDD2-PI. The second control strategy uses the tilt integral derivative with filter (TID-F). The designed controllers employ two distinct metaheuristic computation techniques: grey wolf optimization (GWO) and whale optimization algorithm (WOA) for the parameter tuning. We evaluated the dynamic and steady-state performance of the proposed control strategies using four performance indices. In addition, to analyze the robustness of proposed control strategies, a comprehensive comparison has been performed with a variety of controllers, including tilt integral-derivative (TID), fractional order proportional integral derivative (FOPID), integral-proportional derivative (I-PD), proportional integral-derivative (PI-D), and proportional integral proportional derivative (PI-PD). By comparing different test cases, including the variation in the parameters of the BBS with disturbance, we examine step response, set point tracking, disturbance rejection analysis, and robustness of proposed control strategies. The comprehensive comparison of results shows that WOA-PIDD2-PI-ISE and GWO-TID-F- ISE perform superior. Moreover, the proposed control strategies yield oscillation-free, stable, and quick response, which confirms the robustness of the proposed control strategies to the disturbance, parameter variation of BBS, and tracking performance. The practical implementation of the proposed controllers can be in the field of under actuated mechanical systems (UMS), robotics and industrial automation. The proposed control strategies are successfully tested in MATLAB simulation.

NCT/DKFZ MASTER handbook of interpreting whole-genome, transcriptome, and methylome data for precision oncology.

Analysis of selected cancer genes has become an important tool in precision oncology but cannot fully capture the molecular features and, most importantly, vulnerabilities of individual tumors. Observational and interventional studies have shown that decision-making based on comprehensive molecular characterization adds significant clinical value. However, the complexity and heterogeneity of the resulting data are major challenges for disciplines involved in interpretation and recommendations for individualized care, and limited information exists on how to approach multilayered tumor profiles in clinical routine. We report our experience with the practical use of data from whole-genome or exome and RNA sequencing and DNA methylation profiling within the MASTER (Molecularly Aided Stratification for Tumor Eradication Research) program of the National Center for Tumor Diseases (NCT) Heidelberg and Dresden and the German Cancer Research Center (DKFZ). We cover all relevant steps of an end-to-end precision oncology workflow, from sample collection, molecular analysis, and variant prioritization to assigning treatment recommendations and discussion in the molecular tumor board. To provide insight into our approach to multidimensional tumor profiles and guidance on interpreting their biological impact and diagnostic and therapeutic implications, we present case studies from the NCT/DKFZ molecular tumor board that illustrate our daily practice. This manual is intended to be useful for physicians, biologists, and bioinformaticians involved in the clinical interpretation of genome-wide molecular information.

Research Integrity, Governance and Misconduct.

Null.

In Silico Structural and Functional Analyses of NLRP3 Inflammasomes to Provide Insights for Treating Neurodegenerative Diseases.

Inflammasomes are cytoplasmic intracellular multiprotein complexes that control the innate immune system's activation of inflammation in response to derived chemicals. Recent advancements increased our molecular knowledge of activation of NLRP3 inflammasomes. Although several studies have been done to investigate the role of inflammasomes in innate immunity and other diseases, structural, functional, and evolutionary investigations are needed to further understand the clinical consequences of NLRP3 gene. The purpose of this study is to investigate the structural and functional impact of the NLRP3 protein by using a computational analysis to uncover putative protein sites involved in the stabilization of the protein-ligand complexes with inhibitors. This will allow for a deeper understanding of the molecular mechanism underlying these interactions. It was found that human NLRP3 gene coexpresses with PYCARD, NLRC4, CASP1, MAVS, and CTSB based on observed coexpression of homologs in other species. The NACHT, LRR, and PYD domain-containing protein 3 is a key player in innate immunity and inflammation as the sensor subunit of the NLRP3 inflammasome. The inflammasome polymeric complex, consisting of NLRP3, PYCARD, and CASP1, is formed in response to pathogens and other damage-associated signals (and possibly CASP4 and CASP5). Comprehensive structural and functional analyses of NLRP3 inflammasome components offer a fresh approach to the development of new treatments for a wide variety of human disorders.

Entropy in Education System: Transformation of an Individual Through Meaningful Interactions in a Community of Inquiry.

Every individual is unique and may serve a unique purpose in this life. Education is widely accepted to be the means of transformation of individuals so that they may achieve their unique success or create their own lives. However, not every individual seems to be realizing their true potential. This paper explores the concept of entropy in education system as a force that is usually imagined to oppose realization of potential of an individual during life in this phenomenal world. Alternatively, the same may provide an impetus that is necessary to bring in organization in oneself to realize the hidden potential. A one group Pretest-Posttest quasi-experimental design was used to draw the conclusions on data obtained from participants of workshops in three different modes, viz. face-to-face Pre COVID-19, face-to-face in COVID-19 with SOPs, and online in COVID-19. Realization of an individual's potential was represented as a dependent variable, i.e. transformation in cognition, skills, and attitude while the independent variables taken into account were the meaningful interactions of an individual with peers and advanced learners in a designed environment. It was inferred from the results that transformation in learners' cognition (6-30 %), skills (0-20 %), and attitude (5-32 %) occurred through human discourse, in a community of inquiry.

Sustainable Use of Marble Waste in Industrial Production of Fired Clay Bricks and Its Employment for Treatment of Flue Gases.

In the current study, waste marble powder was utilized to produce lightweight fired clay bricks and in the treatment of flue gases. Marble waste powder used in clay bricks and flue gas treatment was collected from local marble processing plants, and its chemical composition was analyzed using energy-dispersive X-ray analysis and X-ray fluorescence. Clay bricks were produced in local fired clay brick kiln by partial replacement (10-40%) of clay with calcined and uncalcined waste marble powder. The temperature in the firing zone of the kiln was 1000-1100 °C. Clay brick properties such as compressive strength, bulk density, porosity, and water absorption were analyzed. Results show that the porosity of clay bricks increases with an increase in marble waste percentage, and due to an increase in porosity, water absorption of clay bricks also increases, while compressive strength and bulk density decrease. Clay bricks with 10% uncalcined marble waste and 20% calcined marble waste satisfy the required Turkish and European compressive strength standard. Marble waste decreases the concentration of sulfur dioxide and particulate matter in flue gases. There is up to 43 and 65% reduction in the concentration of sulfur dioxide and particulate matters, respectively, in flue gases, after treatment with marble waste. The addition of marble waste to clay bricks is an effective and economical solution for waste marble powder management. Furthermore, it can be used for the treatment of flue gases from brick kilns before its addition to clay bricks.

The role of miR-200b/c in balancing EMT and proliferation revealed by an activity reporter.

Since their discovery, microRNAs (miRNAs) have been widely studied in almost every aspect of biology and medicine, leading to the identification of important gene regulation circuits and cellular mechanisms. However, investigations are generally focused on the analysis of their downstream targets and biological functions in overexpression and knockdown approaches, while miRNAs endogenous levels and activity remain poorly understood. Here, we used the cellular plasticity-regulating process of epithelial-to-mesenchymal transition (EMT) as a model to show the efficacy of a fluorescent sensor to separate cells with distinct EMT signatures, based on miR-200b/c activity. The system was further combined with a CRISPR-Cas9 screening platform to unbiasedly identify miR-200b/c upstream regulating genes. The sensor allows to infer miRNAs fundamental biological properties, as profiling of sorted cells indicated miR-200b/c as a molecular switch between EMT differentiation and proliferation, and suggested a role for metabolic enzymes in miR-200/EMT regulation. Analysis of miRNAs endogenous levels and activity for in vitro and in vivo applications could lead to a better understanding of their biological role in physiology and disease.

Thymidylate synthase drives the phenotypes of epithelial-to-mesenchymal transition in non-small cell lung cancer.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) enhances motility, stemness, chemoresistance and metastasis. Little is known about how various pathways coordinate to elicit EMT's different functional aspects in non-small cell lung cancer (NSCLC). Thymidylate synthase (TS) has been previously correlated with EMT transcription factor ZEB1 in NSCLC and imparts resistance against anti-folate chemotherapy. In this study, we establish a functional correlation between TS, EMT, chemotherapy and metastasis and propose a network for TS mediated EMT. METHODS: Published datasets were analysed to evaluate the significance of TS in NSCLC fitness and prognosis. Promoter reporter assay was used to sort NSCLC cell lines in TSHIGH and TSLOW. Metastasis was assayed in a syngeneic mouse model. RESULTS: TS levels were prognostic and predicted chemotherapy response. Cell lines with higher TS promoter activity were more mesenchymal-like. RNA-seq identified EMT as one of the most differentially regulated pathways in connection to TS expression. EMT transcription factors HOXC6 and HMGA2 were identified as upstream regulator of TS, and AXL, SPARC and FOSL1 as downstream effectors. TS knock-down reduced the metastatic colonisation in vivo. CONCLUSION: These results establish TS as a theranostic NSCLC marker integrating survival, chemo-resistance and EMT, and identifies a regulatory network that could be targeted in EMT-driven NSCLC.

Novel Mutations in NSP1 and PLPro of SARS-CoV-2 NIB-1 Genome Mount for Effective Therapeutics

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the etiologic agent of Coronavirus Disease-2019 (COVID-19), is rapidly accumulating new mutations. Analysis of these mutations is necessary for gaining knowledge regarding different aspects of therapeutic development. Recently, we have reported a Sanger method based genome sequence of a viral isolate named SARS-CoV-2 NIB-1, circulating in Bangladesh. The genome has four novel mutations in V121D, V843F, A889V and G1691C positions. V121D substitution has the potential to destabilize the Non-Structural Protein (NSP-1) which inactivates the type-1 Interferon-induced antiviral system hence this mutant could be the basis of attenuated vaccines against SARS-CoV-V843F, A889V and G1691C are all located in NSP3. G1691C can decrease the flexibility of the protein while V843F and A889V changed the binding pattern of SARS-CoV-2 Papain-Like protease (PLPro) inhibitor GRL0617. V843F PLPro showed reduced affinity for Interferon Stimulating Gene-15 (ISG-15) protein whereas V843F+A889V double mutants exhibited the same binding affinity as wild type PLPro. Here, V843F is a conserved position of PLPro that damaged the structure but A889V, a less conserved residue, most probably neutralized that damage. Mutants of NSP1 could provide attenuated vaccines against coronavirus. Also, these mutations of PLPro could be targeted to develop anti-SARS therapeutics.

Ovarian dermoid cyst presenting with unusual complaint of hair coming out of the anal orifice - A case report.

Dermoid cyst of the ovary is a common benign condition. It is usually asymptomatic but can present with pain, mass, hormone related symptoms or paraneoplastic syndrome. Hair is a common morphological component of the dermoid cyst; however, it rarely manifests as a presenting complain. We report a case, who presented with the complaints of hair coming out through her anal orifice for a year. Ultrasound and computed tomography scan revealed a dermoid cyst of the right ovary adherent to the rectum. Surgical removal showed hair coming out of the cyst. Primary repair of the defect in rectal wall was performed which resulted in resolution of the symptoms.

Post parotidectomy facial nerve palsy: A retrospective analysis.

BACKGROUND &OBJECTIVES: Transient paralysis of facial nerve is seen to vary from 15 % to 66 % in post-parotid surgery. The objective of this study was to find out the complications in post-parotidectomy with regards to facial nerve dysfunction since it is a vital structure encountered in parotid surgeries. METHODS: This was a retrospective study through non probability convenient sampling technique carried from September 2010 to January 2019 in the Department of Otorhinolaryngology, Dow University of Health Sciences, Dr. Ruth K.M.Pfau Civil Hospital, Karachi. Clinical data were recorded from 75 patients and out of them 70 patients had undergone surgery with parotid gland tumours and were reported on the morphology, age, sex, surgical procedure and complications, particularly facial nerve dysfunctions. In most cases ante-grade technique was performed to identify the facial nerve, whereas retrograde technique was used in recurring tumours, and in difficult cases. The stimulator of the nerve has not been used. The nature or severity of Facial nerve dysfunction was assessed in terms of either it is, permanent or temporary, total or incomplete in respect to its branches. RESULTS: Among total 75 patients; the mean age was 38.75 ± 9.26 years with male to female ratio of 1:1. Majority of the patients were diagnosed as pleomorphic adenoma, i.e. 78.6% after which 12% were diagnosed as mucoepidermoid carcinoma. 88.6% of patients had superficial parotidectomy and 11.4% of patients had total parotidectomy. About 75% of patients had no complications. 5(7.1%) patients had complete facial nerve palsy. Damage to the mandibular, buccal and temporozygomatic branch was observed in 10(14%), 2(3%) and 1(1.4%) patients respectively. CONCLUSION: The most prevalent benign parotid tumour in this study was pleomorphic adenoma. After performing parotid surgery, it was predicted that the rate of complications related to the facial nerve injury was reduced as compared to the previous studies.

Influence of temperature on enhancement of volatile fatty acids fermentation from organic fraction of municipal solid waste: Synergism between food and paper components.

This study explores individual contributions and synergistic effects of food and paper, main components of organic fraction of municipal solid waste (OFMSW) towards volatile fatty acids (VFA) fermentation under different temperatures (25, 37, 42 and 52 °C). Thanks to the synergism of food and paper component (FC & PC), the results revealed that OFMSW is suitable for VFA production. Maximum VFA production was noticed to be 21.5 mg/L at 42 °C, ~2.1, and 1.42 times higher than fermentation of PC and FC. Enhanced hydrolysis of PC occurred at >37 °C, increasing alkalinity in leachate to 6.7 g/L at 42 °C, thus maintaining a stable pH (5.4-5.6) during acidogenic fermentation. Additionally, 74% of COD is hydrolyzed, of which 79% is converted to VFA based on biodegradable carbon at 42 °C. It is suggested that co-existence of FC and PC can enhance VFA production of OFMSW, and targeted VFA production can be maximized through process optimization.

Thymidylate synthase maintains the de-differentiated state of triple negative breast cancers.

Cancer cells frequently boost nucleotide metabolism (NM) to support their increased proliferation, but the consequences of elevated NM on tumor de-differentiation are mostly unexplored. Here, we identified a role for thymidylate synthase (TS), a NM enzyme and established drug target, in cancer cell de-differentiation and investigated its clinical significance in breast cancer (BC). In vitro, TS knockdown increased the population of CD24+ differentiated cells, and attenuated migration and sphere-formation. RNA-seq profiling indicated repression of epithelial-to-mesenchymal transition (EMT) signature genes upon TS knockdown, and TS-deficient cells showed an increased ability to invade and metastasize in vivo, consistent with the occurrence of a partial EMT phenotype. Mechanistically, TS enzymatic activity was found essential for maintenance of the EMT/stem-like state by fueling a dihydropyrimidine dehydrogenase-dependent pyrimidine catabolism. In patient tissues, TS levels were found significantly higher in poorly differentiated and in triple negative BC, and strongly correlated with worse prognosis. The present study provides the rationale to study in-depth the role of NM at the crossroads of proliferation and differentiation, and depicts new avenues for the design of novel drug combinations for the treatment of BC.

Localized Injection of Streptomycin, Kenacort and Lidocaine combination for Symptomatic Pain Management of Knee Osteoarthritis.

OBJECTIVE: To determine the frequency of reduction of pain in symptomatic knee osteoarthritis by using combination injections. METHODS: The experimental study was conducted from January 1, 2010, to December 31, 2016,at Al-Noor Surgery Hospital, Chakwal, Pakistan, and comprised patients suffering from symptomatic knee osteoarthritis. All patients were injected intra-articularly and peri-articularily with a combination of streptomycin, kenacort and lidocaine. The effects of this injection were recorded immediately after injection, after a month and after a year. Data was analyzed using SPSS 21. RESULTS: Of the 169 patients, there were 70(41.40%) males and 99(58.60%) females. The overall mean age and pain duration was 59.27±7.79 years and10.5±5.1 years respectively. No patient had pain immediately after the injection and after a month of follow-up. After a year, 145(86%) had a complete loss of pain compared to the baseline. Three (1.77%) patients required repetition of injection after a year. None of the patients suffered from septic arthritis or localised flare-ups and no one opted for knee joint arthoplasty. CONCLUSIONS: Combination of streptomycin, low-dose corticosteroids and lidocaine hadimmediate and prolonged effect in reducing pain in patients with knee osteoarthritis.

Program to Improve Private Early Education (PIPE): a case study of a systems approach for scaling quality early education solutions.

FSG is a mission-driven nonprofit organization supporting leaders in creating large-scale, lasting social change. A survey conducted by FSG in 2015 across 4407 low-income families in urban India showed that 95% of them send their children to preschools, a majority of choosing affordable private preschools (APSs), as parents perceive the quality of government schools to be poor. Parents use and value rote-based methods (e.g., reciting poems) to assess their children's learning in school; however, these methods fail to measure conceptual understanding. The APS system delivers on these rote approaches using inappropriate pedagogy, leading to poor learning outcomes. Affordable high-quality activity-based preschool solutions exist and could be brought to the APS to significantly improve the classroom environment and learning outcomes. This requires changing mindsets of all actors-solution provider companies, APS owners, APS teachers, and low-income parents. We present FSG's approach to shaping demand for quality preschool services and to improve learning outcomes in urban Indian APSs through the implementation of the pilot Program to Improve Private Early Education (PIPE).

Ameliorative effect of chitosan-conjugated 17α-methyltestosterone on testicular development in Clarias batrachus.

Chitosan nanoparticles conjugated with 17α-methyltestosterone (CS + MT) were used for studying their effect on the testicular development of Clarias batrachus during different reproductive phases. The size of chitosan nanoparticles was 127.2 nm and the nano-conjugated 17α methyltestosterone (17α-MT) was 196.1 nm (20 mg/100 ml of chitosan). Single injections of CS + MT at different doses such as 0.01, 0.1 and 0.5 µg/g body weight were administered to adults during the pre-spawning, spawning and post-spawning phase. Nano-conjugated steroid was effective at the lower dose; showing an increase in the Gonadosomatic Index (GSI) and 11-ketotestosterone level compared to the control group. Histological observations confirmed the dose-dependent advancement in spermatogenesis. These findings indicate the possibility of using CS + MT for enhancing gonadal maturity of C. batrachus.

Post-PCNL Renal Artery Pseudoanurysm.

A renal artery pseudoaneurysm is a rare but important complication that can occur after renal trauma, renal biopsy, percutaneous nephrostomy, percutaneous nephrolithotomy (PCNL), and partial nephrectomy. The incidence of this potentially life-threatening complication is less than 1%, but is likely to increase with the increasing popularity of endoscopic renal procedures. We present a case of a 30-year female who underwent right PCNL for a right renal pelvic stone. Two weeks later, she presented with massive hematuria. Renal angiography revealed psuedoanurysm of interlobar artery which was successfully treated with coil embolization.