An Energy Efficient and Temperature Stable Digital FLL-based Wakeup Timer with Time-Domain Temperature Compensation.

This brief presents an on-chip digital intensive frequency-locked loop (DFLL)-based wakeup timer with a time-domain temperature compensation featuring a embedded temperature sensor. The proposed compensation exploits the deterministic temperature characteristics of two complementary resistors to stabilize the timer's operating frequency across the temperature by modulating the activation time window of the two resistors. As a result, it achieves a fine trimming step (± 1 ppm), allowing a small frequency error after trimming (<± 20 ppm). By reusing the DFLL structure, instead of employing a dedicated sensor, the temperature sensing operates in the background with negligible power (2 %) and hardware overhead (< 1 %). The chip is fabricated in 40 nm CMOS, resulting in 0.9 pJ/cycle energy efficiency while achieving 8 ppm/ºC from -40ºC to 80ºC.

Binding and displacement study of gentamicin, 5-fluorouracil, oxytetracycline and rolitetracycline with (BSA: Drug2) complex using spectroscopic and calorimetric techniques: Biophysical approach.

Understanding of energetics of interactions between drug and protein is essential in pharmacokinetics and pharmacodynamics study. The binding affinity (K) helps in investigating how tightly or loosely drug is bound to protein. The binding, displacement, conformational change and stability study of drugs- gentamicin (GM), 5-Fluorouracil (5FU), oxytetracycline (OTC) and rolitetracycline (RTC) with bovine serum albumin (BSA) has been carried out in presence of each other drug by fluorescence, UV-visible spectroscopy, molecular docking, circular dichroism techniques and thermal denaturation method. The site marker study and docking methods have confirmed that 5FU and GM are able to bind at site 1 and OTC and RTC at site II of BSA. The order of their binding affinities with BSA for the binary system were as GM <5FU < OTC < RTC with the order of 102 < 103 < 105 < 105-6 M-1. The displacement study has shown that higher affinity drug decreases the equilibrium constant of another drug already in bound state with BSA if both these drugs are having the same binding site. Therefore 5FU, GM (binding site 1) drugs were not able to displace OTC and RTC (binding site 2) and vice-versa as they are binding at two different sites. The binding constant values were found to be decreasing with increasing temperature for all the systems involved which suggests static or mixed type of quenching, however can only confirmed with the help of TCSPC technique. The ΔG0 (binding energy) obtained from docking method were in accordance with the ITC method. From molecular docking we have determined the amino acid residues involved in binding process for binary and ternary systems by considering first rank minimum binding energy confirmation. From CD it has been observed that RTC causes most conformational change in secondary and tertiary structure of BSA due to the presence of pyrrole ring. OTC-RTC with higher affinity showed highest melting temperature Tm values while low affinity drugs in (5FU-GM) combination showed lowest Tm value. 5FU showed large endothermic denaturation enthalpy ΔHd0 due to the presence of highly electronegative fluorine atom in the pyridine analogue.

Laboratory Investigations of the Leica RTC360 Laser Scanner-Distance Measuring Performance.

A Leica RTC360 laser scanner was investigated using a linear horizontal comparator system with four targets of different reflectance. Several thousand panorama scans were conducted along the 30 m long comparator, basically in 40 mm steps. For a selected target, more detailed investigations were carried out with a 2 mm step width for a 2 m wide section. The absolute offset between the scanner and the relative interferometer measurements was determined with a calibrated total station. The investigations revealed several systematic effects like an offset in the distance measurement of about 1.3 mm. Furthermore, sections with stochastic behavior as well as sections with pseudo-cyclic parts were observed, depending on the reflectance of the target. The deterministic sections showed curved and striped patterns with some discontinuities of about 2 mm at 20 m, resulting in a saw-tooth like pattern along the distances. Within all the experiments, the distance deviations were below the manufacturer specifications of the 3D point accuracy. However, it was demonstrated that the distance measurements had clear systematic components. In using these new findings, the specification of the measurement "noise" in the data sheet has to be seen as critical.

Smart roofs featuring predictive control: An upgrade for mitigating precipitation extreme-induced pluvial floods.

In the face of escalating urban pluvial floods exacerbated by climate change, conventional roof systems fall short of effectively managing precipitation extremes. This paper introduces a smart predictive solution: the Smart Internal Drainage Roof (SIDR) system, which leverages forecasted data to enhance the mitigation of pluvial floods in Central Business District (CBD) areas. Unlike traditional approaches, SIDRs utilize a synergistic combination of Rule-based Control (RBC) and Model Predictive Control (MPC) algorithms, tailored to optimize the operational efficiency of both grey and green roofs. Within the examined 1.3 km2 area in Beijing, China, SIDRs, covering 11% of the site, decreased total flooded areas by 30%-50% and eliminated 60%-100% of high-risk zones during three actual events. Moreover, SIDRs streamlined outflow processes without extending discharge time and reduced flood duration at a high-risk underpass by more than half. The SIDR's distinct features, including a high control resolution of 5 min, integration with existing waterproofs, and advanced 2D dynamic runoff visualization, position it as a scalable and cost-efficient upgrade in urban flood resilience strategies.

Realising smarter stormwater management: A review of the barriers and a roadmap for real world application.

Effective management of stormwater systems is necessary for protection of both the built and natural environments. However, stormwater management is facing multiple, growing challenges, including climate change, ageing infrastructure, population growth, urbanisation, environmental concerns, regulatory and institutional changes and public awareness. While the potential of 'smart', internet-of-things enabled stormwater management systems to address these challenges is increasingly being recognised, with considerable evidence in literature for the benefits of more data-driven approaches, implementation to date remains low. This paper, therefore, provides a comprehensive review of the potential barriers to adoption of smarter stormwater management practices that require addressing, and provides a roadmap for real world application. Barriers related to all elements of stormwater management, from the asset sensing to the data analytics and online optimisation, are identified. Technical challenges discussed include the availability and reliability of technologies, technological and physical limitations, decision making, uncertainty and security. Technical barriers are rapidly reducing and there is increasing evidence in the academic literature of the efficacy of smart technologies. However, socio-economic barriers remain a significant challenge, and issues such as trust and lack of confidence, resistance to change, expense, and lack of knowledge and guidance are reviewed. A 'smart stormwater management wheel' that provides a flexible and iterative approach for implementing smart functionality is also presented. Whilst acting as a roadmap, this aims to facilitate a structured methodology for overcoming barriers and benchmarking progress, and may be used to explore trade-offs and relationships between differing levels of implementation for each of the constituent technologies in a smart stormwater system.

Utilising Sentinel-1's Orbital Stability for Efficient Pre-Processing of Radiometric Terrain Corrected Gamma Nought Backscatter.

Radiometric Terrain Corrected (RTC) gamma nought backscatter, which was introduced around a decade ago, has evolved into the standard for analysis-ready Synthetic Aperture Radar (SAR) data. While working with RTC backscatter data is particularly advantageous over undulated terrain, it requires substantial computing resources given that the terrain flattening is more computationally demanding than simple orthorectification. The extra computation may become problematic when working with large SAR datasets such as the one provided by the Sentinel-1 mission. In this study, we examine existing Sentinel-1 RTC pre-processing workflows and assess ways to reduce processing and storage overheads by considering the satellite's high orbital stability. By propagating Sentinel-1's orbital deviations through the complete pre-processing chain, we show that the local contributing area and the shadow mask can be assumed to be static for each relative orbit. Providing them as a combined external static layer to the pre-processing workflow, and streamlining the transformations between ground and orbit geometry, reduces the overall processing times by half. We conducted our experiments with our in-house developed toolbox named wizsard, which allowed us to analyse various aspects of RTC, specifically run time performance, oversampling, and radiometric quality. Compared to the Sentinel Application Platform (SNAP) this implementation allowed speeding up processing by factors of 10-50. The findings of this study are not just relevant for Sentinel-1 but for all SAR missions with high spatio-temporal coverage and orbital stability.

Comparing the effect of the Model of Therapeutic Engagement in cardiac rehabilitation on the sense of coherence and adherence to treatment: a randomized clinical trial.

PURPOSE: The study aimed to compare the effectiveness of a traditional cardiac rehabilitation (CR) program with an enhanced program incorporating the model of therapeutic engagement (MTE) and extended remote support for patients undergoing coronary artery bypass graft (CABG) patients. MATERIALS AND METHODS: In a randomized controlled trial, 88 CABG patients were assigned to experimental and control groups. The experimental group received integrated MTE cardiac rehabilitation, and assessments were conducted at three time points: pre-CR, one month later, and three months post-CR. The study measured medication adherence (MARS-5) and sense of coherence (SoC-13) scales. RESULTS: The study found no significant differences in demographic factors between the experimental and control groups. However, significant differences were observed in MARS and individuals' SoC scores over time in the experimental group, with notable improvements (p < 0.001). The control group showed significant changes only up to one month. Group effects were evident, with consistent increases in the experimental group's outcomes at each assessment point. CONCLUSION: Integrating the MTE into CR programs offers benefits in terms of medication adherence and individuals' sense of coherence, which warrants further investigation and clinical implementation.

Cardiac rehabilitation (CR) is recognized as one of the most effective interventions for secondary prevention, but its accessibility is limited in middle-income countries (MICs).This study represents one of the first theoretically-informed CR trials in a MIC that incorporates the model of therapeutic engagement (MTE) combined with extended remote support services into CR program.The MTE model, as a theoretical framework, was highly suitable for CR settings and demonstrated favorable outcomes.This approach has the potential to greatly benefit cardiac patients, particularly those who may initially show hesitance or reluctance towards engaging in CR.

Maxillofacial fractures in Pondicherry, India: An eight-year single centre retrospective study.

Background: The purpose of the present study was to analyze the etiology, incidence, pattern, and treatment modalities of patients with maxillofacial fractures treated at the Department of Dentistry of a medical college in Pondicherry during the period between June 2011 and June 2019. Materials and Methods: A retrospective epidemiological study of 277 patients treated for maxillofacial fractures between June 2011 and June 2019 was performed. Data regarding age, gender, etiology, site of the fracture, time of injury, presence of associated injuries, treatment modalities, and complications were recorded. Results: A total of 491 maxillofacial fractures were seen in 277 patients. These were 261 males (94.2%) and 16 females (5.8%) with a male to female ratio of 16.3:1. Most of the patients 79.8% were in the age group of 11 to 40 years. Most common cause of injury was Road Traffic Collisions (RTCs; 62.1%), followed by fall (20.2%), assault (14.4%) and others (3.3%). Fractures of the mandible (52.3%) and zygomatic complex (18.9%) were the most common maxillofacial fractures reported in our study. 196 patients sustained associated injuries with a prevalence of soft tissue injury (61.2%). Majority of fractures were treated with open reduction and internal fixation (ORIF; 71.9%) of patients followed by closed reduction (17.7%) and observation only (10.4%). Postoperative complications were presented in 16.8% of the patients in the study. Conclusion: RTC is the commonest cause of maxillofacial injury with a male predominance in our study. Mandibular and zygomatic complex fractures were the most common. ORIF remains the preferred method of treatment.s.

Systematic review and meta-analysis of the prevalence of the retrotransverse foramen of the atlas.

The retrotransverse foramen (RTF) is a nonmetric variant of the atlas vertebra that can accommodate an anastomotic vertebral vein and occipital nerve. An understanding of this variation and its occurrence is crucial, as it could aid in explanation of the unidentified cause of the high prevalence of variability in this region. The aim of this meta-analysis was to obtain data on the prevalence of the RTF and its variations according to anatomy, sex, and ethnicity. A large-scale search was conducted through the major online databases to establish and determine the pool of studies reporting data relevant to the RTF. No date or language restrictions were applied. The data collection was categorized by prevalence, type (incomplete/complete), side, sex, ethnicity, laterality, and diameter. A total of 17 studies (n = 1979 subjects) were incorporated into our analysis. The overall pooled prevalence for a complete RTF was 11.4% and the overall pooled prevalence of an incomplete (partial) RTF was 9.6%. A complete RTF was most prevalent in Africa (Sub-Saharan population) (12.1%), followed by Europe (11.8%) and Asia (9.7%). As this variant occurs in a significant number of patients in all of the aforementioned populations, recognition, and awareness, especially with thorough investigation with computer tomography angiography (CTA) should be implemented, as it is the only possible way to visualize the possible contents of RTF.

A Low-Power Hardware Architecture for Real-Time CNN Computing.

Convolutional neural network (CNN) is widely deployed on edge devices, performing tasks such as objective detection, image recognition and acoustic recognition. However, the limited resources and strict power constraints of edge devices pose a great challenge to applying the computationally intensive CNN models. In addition, for the edge applications with real-time requirements, such as real-time computing (RTC) systems, the computations need to be completed considering the required timing constraint, so it is more difficult to trade off between computational latency and power consumption. In this paper, we propose a low-power CNN accelerator for edge inference of RTC systems, where the computations are operated in a column-wise manner, to realize an immediate computation for the currently available input data. We observe that most computations of some CNN kernels in deep layers can be completed in multiple cycles, while not affecting the overall computational latency. Thus, we present a multi-cycle scheme to conduct the column-wise convolutional operations to reduce the hardware resource and power consumption. We present hardware architecture for the multi-cycle scheme as a domain-specific CNN architecture, which is then implemented in a 65 nm technology. We prove our proposed approach realizes up to 8.45%, 49.41% and 50.64% power reductions for LeNet, AlexNet and VGG16, respectively. The experimental results show that our approach tends to cause a larger power reduction for the CNN models with greater depth, larger kernels and more channels.

Targeting viral proteins for restraining SARS-CoV-2: focusing lens on viral proteins beyond spike for discovering new drug targets.

INTRODUCTION: Emergence of highly infectious SARS-CoV-2 variants are reducing protection provided by current vaccines, requiring constant updates in antiviral approaches. The virus encodes four structural and sixteen nonstructural proteins which play important roles in viral genome replication and transcription, virion assembly, release , entry into cells, and compromising host cellular defenses. As alien proteins to host cells, many viral proteins represent potential targets for combating the SARS-CoV-2. AREAS COVERED: Based on literature from PubMed and Web of Science databases, the authors summarize the typical characteristics of SARS-CoV-2 from the whole viral particle to the individual viral proteins and their corresponding functions in virus life cycle. The authors also discuss the potential and emerging targeted interventions to curb virus replication and spread in detail to provide unique insights into SARS-CoV-2 infection and countermeasures against it. EXPERT OPINION: Our comprehensive analysis highlights the rationale to focus on non-spike viral proteins that are less mutated but have important functions. Examples of this include: structural proteins (e.g. nucleocapsid protein, envelope protein) and extensively-concerned nonstructural proteins (e.g. NSP3, NSP5, NSP12) along with the ones with relatively less attention (e.g. NSP1, NSP10, NSP14 and NSP16), for developing novel drugs to overcome resistance of SARS-CoV-2 variants to preexisting vaccines and antibody-based treatments.

Glycyrrhizin as a promising kryptonite against SARS-CoV-2: Clinical, experimental, and theoretical evidences.

COVID-19 is the most devastating disease in recent times affecting most people globally. The higher rate of transmissibility and mutations of SARS-CoV-2 along with the lack of potential therapeutics has made it a global crisis. Potential molecules from natural sources could be a fruitful remedy to combat COVID-19. This systematic review highlights the detailed therapeutic implication of naturally occurring glycyrrhizin and its related derivatives against COVID-19. Glycyrrhizin has already been established for blocking different biomolecular targets related to the SARS-CoV-2 replication cycle. In this article, several experimental and theoretical evidences of glycyrrhizin and related derivatives have been discussed in detail to evaluate their potential as a promising therapeutic strategy against COVID-19. Moreover, the implication of glycyrrhizin in traditional Chinese medicines for alleviating the symptoms of COVID-19 has been reviewed. The potential role of glycyrrhizin and related compounds in affecting various stages of the SARS-CoV-2 life cycle has also been discussed in detail. Derivatization of glycyrrhizin for designing potential lead compounds along with combination therapy with other anti-SARS-CoV-2 agents followed by extensive evaluation may assist in the formulation of novel anti-coronaviral therapy for better treatment to combat COVID-19.

Clinical trial data-sharing policies among journals, funding agencies, foundations, and other professional organizations: a scoping review.

BACKGROUND AND OBJECTIVES: To identify the similarities and differences in data-sharing policies for clinical trial data that are endorsed by biomedical journals, funding agencies, and other professional organizations. Additionally, to determine the beliefs, and opinions regarding data-sharing policies for clinical trials discussed in articles published in biomedical journals. METHODS: Two searches were conducted, a bibliographic search for published articles that present beliefs, opinions, similarities, and differences regarding policies governing the sharing of clinical trial data. The second search analyzed the gray literature (non-peer-reviewed publications) to identify important data-sharing policies in selected biomedical journals, foundations, funding agencies, and other professional organizations. RESULTS: A total of 471 articles were included after database search and screening, with 45 from the bibliographic search and 426 from the gray literature search. A total of 424 data-sharing policies were included. Fourteen of the 45 published articles from the bibliographic search (31.1%) discussed only advantages specific to data-sharing policies, 27 (27/45; 60%) discussed both advantages and disadvantages, and 4 (4/45; 8.9%) discussed only disadvantages specific. A total of 216 journals (of 270; 80%) specified a data-sharing policy provided by the journal itself. One hundred industry data-sharing policies were included, and 32 (32%) referenced a data-sharing policy on their website. One hundred and thirty-six (42%) organizations (of 327) specified a data-sharing policy. CONCLUSION: We found many similarities listed as advantages to data-sharing and fewer disadvantages were discussed within the literature. Additionally, we found a wide variety of commonalities and differences-such as the lack of standardization between policies, and inadequately addressed details regarding the accessibility of research data-that exist in data-sharing policies endorsed by biomedical journals, funding agencies, and other professional organizations. Our study may not include information on all data sharing policies and our data is limited to the entities' descriptions of each policy.

Emergence and spreading of the largest SARS-CoV-2 deletion in the Delta AY.20 lineage from Uruguay.

The genetic variability of SARS-CoV-2 (genus Betacoronavirus, family Coronaviridae) has been scrutinized since its first detection in December 2019. Although the role of structural variants, particularly deletions, in virus evolution is little explored, these genome changes are extremely frequent. They are associated with relevant processes, including immune escape and attenuation. Deletions commonly occur in accessory ORFs and might even lead to the complete loss of one or more ORFs. This scenario poses an interesting question about the origin and spreading of extreme structural rearrangements that persist without compromising virus viability. Here, we analyze the genome of SARS-CoV-2 in late 2021 in Uruguay and identify a Delta lineage (AY.20) that experienced a large deletion (872 nucleotides according to the reference Wuhan strain) that removes the 7a, 7b, and 8 ORFs. Deleted viruses coexist with wild-type (without deletion) AY.20 and AY.43 strains. The Uruguayan deletion is like those identified in Delta strains from Poland and Japan but occurs in a different Delta clade. Besides providing proof of the circulation of this large deletion in America, we infer that the 872-deletion arises by the consecutive occurrence of a 6-nucleotide deletion, characteristic of delta strains, and an 866-nucleotide deletion that arose independently in the AY.20 Uruguayan lineage. The largest deletion occurs adjacent to transcription regulatory sequences needed to synthesize the nested set of subgenomic mRNAs that serve as templates for transcription. Our findings support the role of transcription sequences as a hotspot for copy-choice recombination and highlight the remarkable dynamic of SARS-CoV-2 genomes.

Slower progression of amyotrophic lateral sclerosis with external application of a Chinese herbal plaster-The randomized, placebo-controlled triple-blinded ALS-CHEPLA trial.

Background: Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterized by gradually increasing damage to the upper and lower motor neurons. However, definitive and efficacious treatment for ALS is not available, and oral intake in ALS patients with bulbar involvement is complicated due to swallowing difficulties. Hypothesis/purpose: This study investigated whether the external plaster application of the herbal composition Ji-Wu-Li efficiently slows ALS progression because prior studies obtained promising evidence with oral herbal applications. Study design: The randomized, triple-blinded study compared the efficacy, safety, and tolerability of the application of Ji-Wu-Li plaster (JWLP) with placebo plaster (PLAP). Methods: In total, 120 patients with definite ALS, clinically probable ALS, or clinically probable laboratory-supported ALS were randomized in a 1:1 ratio to receive JWLP or PLAP. Patients were treated and observed for 20 weeks. The primary outcome was the ALSFRS-R score, while the secondary outcomes were the ALS-SSIT score and weight loss. Results: The mean±SD decrease in the ALSFRS-R over 20 weeks differed by 0.84 points in a group comparison (JWLP, -4.44 ± 1.15; PLAP, -5.28 ± 1.98; p = 0.005). The mean increase in the ALS-SSIT over 20 weeks differed by 2.7 points in a group comparison (JWLP, 5.361.15; PLAP, 8.06 ± 1.72; p < 0.001). The mean weight loss over 20 weeks differed by 1.65 kg in a group comparison (JWLP, -3.98 ± 2.61; PLAP, -5.63 ± 3.17; p = 0.002). Local allergic dermatitis suspected as causal to the intervention occurred in 10 of 60 participants in the JWLP group and 9 of 60 participants in the PLAP group. Systemic adverse events were mild, temporary, and considered unrelated to the intervention. Conclusion: The JWLP showed clinical efficacy in the progression of ALS, as measured by the ALSFRS-R, ALS-SSIT, and weight loss in a randomized, placebo-controlled trial. Because skin reactions occurred in both groups, the covering material needs improvement. All of the Ji Wu Li herbal ingredients regulate multiple mechanisms of neurodegeneration in ALS. Hence, JWLP may offer a promising and safe add-on therapy for ALS, particularly in patients with bulbar involvement, but a confirmative long-term multicentre study is required.

Therapeutic approaches and vaccination in fighting COVID-19 infections: A review.

Coronavirus disease 2019 (COVID-19) is a remarkably contagious and pathogenic viral infection arising from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first appeared in Wuhan, China. For the time being, COVID-19 is not treated with a specific therapy. The Food and Drug Administration (FDA) has approved Remdesivir as the first drug to treat COVID-19. However, many other therapeutic approaches are being investigated as possible treatments for COVID-19. As part of this review, we discussed the development of various drugs, their mechanism of action, and how they might be applied to different cases of COVID-19 patients. Furthermore, this review highlights an update in the emergence of new prophylactic or therapeutic vaccines against COVID-19. In addition to FDA or The World Health Organization (WHO) approved vaccines, we intended to incorporate the latest published data from phase III trials about different COVID-19 vaccines and provide clinical data released on the networks or peer-review journals.

Moving to a future of smart stormwater management: A review and framework for terminology, research, and future perspectives.

Stormwater hazards are a significant threat across the globe. These are continuing to increase in line with urbanisation and climate change, leading to a recognition that the historic paradigm of passive management using centralised infrastructure is insufficient to manage future hazards to our society, environment, and economy. The cross-sector Internet of Things revolution has inspired a new generation of smart stormwater management systems which offer an effective, cost beneficial and adaptive solution to enhance network capacities and reduce hazards. However, despite growing prominence within research, this technology remains under-utilised, in a large part due to fragmented and inconsistent alignment and terminology, obscuring the strategic co-ordination of research. We respond to this through systematically reviewing the terminology, practice and trajectory for smart stormwater management and developing a framework which can be applied to both coordinate and understand the existing research landscape, as well as identifying key research gaps for future development. We find that literature almost universally agrees that smart technology is, or will be, beneficial to stormwater management and that technology has reached partial maturity in terms of quantity management, although this has not yet transferred to water quality. However, research is dominated by proof-of-concept modelling studies, with limited practical application beyond real time control of large assets, individual pilot studies and monitoring. We recommend that future research explores and evidences the substantial benefits likely through expanding current implementation towards a coordinated, decentralised, and optimised catchment-scale approach.

The status and analysis of common mutations found in the SARS-CoV-2 whole genome sequences from Bangladesh.

Rapid emergence of covid-19 variants by continuous mutation made the world experience continuous waves of infections and as a result, a huge number of death-toll recorded so far. It is, therefore, very important to investigate the diversity and nature of the mutations in the SARS-CoV-2 genomes. In this study, the common mutations occurred in the whole genome sequences of SARS-CoV-2 variants of Bangladesh in a certain timeline were analyzed to better understand its status. Hence, a total of 78 complete genome sequences available in the NCBI database were obtained, aligned and further analyzed. Scattered Single Nucleotide Polymorphisms (SNPs) were identified throughout the genome of variants and common SNPs such as: 241:C>T in the 5'UTR of Open Reading Frame 1A (ORF1A), 3037: C>T in Non-structural Protein 3 (NSP3), 14,408: C>T in ORF6 and 23,402: A>G, 23,403: A>G in Spike Protein (S) were observed, but all of them were synonymous mutations. About 97% of the studied genomes showed a block of tri-nucleotide alteration (GGG>AAC), the most common non-synonymous mutation in the 28,881-28,883 location of the genome. This block results in two amino acid changes (203-204: RG>KR) in the SR rich motif of the nucleocapsid (N) protein of SARS-CoV-2, introducing a lysine in between serine and arginine. The N protein structure of the mutant was predicted through protein modeling. However, no observable difference was found between the mutant and the reference (Wuhan) protein. Further, the protein stability changes upon mutations were analyzed using the I-Mutant2.0 tool. The alteration of the arginine to lysine at the amino acid position 203, showed reduction of entropy, suggesting a possible impact on the overall stability of the N protein. The estimation of the non-synonymous to synonymous substitution ratio (dN/dS) were analyzed for the common mutations and the results showed that the overall mean distance among the N-protein variants were statistically significant, supporting the non-synonymous nature of the mutations. The phylogenetic analysis of the selected 78 genomes, compared with the most common genomic variants of this virus across the globe showed a distinct cluster for the analyzed Bangladeshi sequences. Further studies are warranted for conferring any plausible association of these mutations with the clinical manifestation.

Identification of Papain-Like Protease inhibitors of SARS CoV-2 through HTVS, Molecular docking, MMGBSA and Molecular dynamics approach.

Coronaviruses (CoVs) are a large group of enveloped positive sense single-stranded RNA viruses that can cause disease to humans. These are zoonotic having potential to cause large-scale outbreaks of infections widely causing morbidity and mortality. Papain-Like Protease (PLpro) is a cysteine protease, essential for viral replication and proliferation, as a highly conserved enzyme it cleaves peptide linkage between Nsp1, Nsp2, Nsp3, and Nsp4. As a valid therapeutic target, it stops viral reproduction and boosts host immune response thereby halting further spread of infection. In the purpose of identifying inhibitors targeting Papain-Like Proteases (PLpro) we initiated a high throughput virtual screening (HTVS) protocol using a SuperNatural Database. The XP docking results revealed that two compounds SN00334175 and SN00162745 exhibited docking scores of -10.58 kcal/mol and -9.93 kcal/mol respectively. The Further PRIME MMGB-SA studies revealed Van der Waal energy and hydrophobic energy terms as major contributors for total binding free energy. The 100 ns molecular dynamics simulation of SN00334175/7JN2 and SN00162745/7JN2 revealed that these complexes were stabilized with ligand binding forming interactions with Gly266, Asn267, Tyr268, Tyr273, Thr301 and Asp302, Lys157, Leu162, Asp164, Arg166, Glu167, Pro248 and Tyr264.

Design and Simulation Study of the Induction Heated Injection Mold with Sliders.

In order to increase the quality of the products manufactured by injection molding, RTC technology can be used to achieve higher mold temperatures. As a result, the path of the injected melt can be extended, allowing the production of parts with more complex shapes and greater length. Induction heating allows heating only selected forming surfaces of the mold which increases the speed and efficiency of the process. This paper presents the concept of a detachable inductor integrated with sliders to enable the application of this technology in an injection mold with sliders, along with the theoretical model used to perform the tests. First, the effect of the magnetic concentrator shape on the process was analyzed. This was followed by a simulation study of the influence of process parameters: heating time, frequency, and electric current. An extensive analysis of the test results of the temperature distribution on the insert allowed for the selection of parameter sets that would enable obtaining the desired surface temperature without a major increase in process time. The results of simulation studies confirm the possible applications and present the range of parameters for obtaining the optimal process.