The main protease of SARS-CoV-2 (called Mpro or 3CLpro) is essential for processing polyproteins encoded by viral RNA. Macromolecules adopt several favored conformations in solution depending on their structure and shape, determining their dynamics and function. Integrated methods combining the lowest-frequency movements obtained by Normal Mode Analysis (NMA), and the faster movements from Molecular Dynamics (MD), and data from biophysical techniques, are necessary to establish the correlation between complex structural dynamics of macromolecules and their function. In this article, we used a hybrid simulation method to sample the conformational space to characterize the structural dynamics and global motions of WT SARS-CoV-2 Mpro and 48 mutants, including several mutations that appear in P.1, B.1.1.7, B.1.351, B.1.525 and B.1.429+B.1.427 variants. Integrated Hybrid methods combining NMA and MD have been useful to study the correlation between the complex structural dynamics of macromolecules and their functioning mechanisms. Here, we applied this hybrid approach to elucidate the effects of mutation in the structural dynamics of SARS-CoV-2 Mpro, considering their flexibility, solvent accessible surface area analyses, global movements, and catalytic dyad distance. Furthermore, some mutants showed significant changes in their structural dynamics and conformation, which could lead to distinct functional properties.

This is a review of the article "It’s Time to Talk About HPC Storage: Perspectives on the Past and Future," for the Leadership Computing department.Comments:Great article! I have only a few small suggestions for clarity/readability below. Abstract: suggest changing "especially as relates to the use of HPC" to "especially related to the use of HPC"paragraph 2: " ORNL Health Data Sciences Institute" -> "Oak Ridge National Laboratory (ORNL) Health Data Sciences Institute"Fig 2 caption: "Each access must traverse multiple distinct protocol hops, with its own interrupt processing, buffering, handshaking, serialization, and access control conventions  " The "its" is ambiguous here, suggest " Each access must traverse multiple distinct protocol hops, where each protocol hop has its own interrupt processing, buffering, handshaking, serialization, and access control conventions ." First paragraph in section "Emerging Challenges in HPC Storage": " Specifically, storage servers were designed to mediate all access to hard drives. By doing so, they could shape traffic (e.g., serializing and batching), buffer data (e.g., caching based on locality), and process I/O requests on more powerful host CPUs (e.g., handling interrupts, packing and unpacking Remote Procedure Call (RPC) requests, and enforcing authorization) to make the most of hard drive capabilities."  Suggest a couple filler words for clarity: " Specifically, storage servers were designed to mediate all access to hard drives. By doing so, they could shape traffic (e.g., by serializing and batching requests), buffer data (e.g., through caching based on locality), and process I/O requests on more powerful host CPUs (e.g., by handling interrupts, packing and unpacking Remote Procedure Call (RPC) requests, and enforcing authorization) to make the most of hard drive capabilities.    "Subsection headers throughout use inconsistent capitalization. I am not certain on the magazine style preference but from the department template it looks like capitalizing the first word and lowercase for the rest of the words is preferred for subsections, e.g., "Low Latency access to Storage" => "Low latency access to storage" In the paragraph beginning " From a device interface perspective, storage system", suggest adding a comma to this clause between "computation" and "reducing": "...  that affects device performance and cost, and as storage becomes disaggregated from computation, reducing data movement between the device and host becomes crucial.    "Same paragraph as above comment, for sentence "...     but recently most storage abstraction innovation has occurred elsewhere, with cloud service providers offering column stores, document stores, key-value stores, streaming data infrastructure, and object stores just to name a few options." Suggest rewording slightly to "...      but recently most storage abstraction innovation has occurred elsewhere, with cloud service providers offering numerous options including column stores, document stores, key-value stores, streaming data infrastructure, and object stores." Or maybe it would be clearer with a comma before "just to name a few options."

A document by Muhammad Anwar Hossain, written on Authorea.

Maxillary sinus melanoma is a rare mucosal melanoma difficult to diagnose in the absence of pigmentation. Intranasal masses presenting with the features of occult malignancy and rapid progression should always be investigated in the line of melanoma irrespective of pigmentation. The histopathological and immunohistochemical examination helps to confirm the diagnosis.

Climate change (CC) can alter the configuration of marine ecosystems, however ecosystem response and resilience to change are usually case-specific. The effect of CC on the demersal resources of the Aegean Sea (east Mediterranean Sea) was investigated during the past six decades applying a combination of multivariate analysis, non-additive modelling and the Integrated Resilience Assessment (IRA) framework. We focused on the study of: (i) the biological ‘system’ complex, using proxies of biomass (landings per unit of capacity) for 12 demersal taxa and (ii) the environmental ‘stressor’ complex, described by 12 abiotic variables. Pronounced changes have occurred in both the environmental and biological system over the studied period. The majority of the environmental stressors exhibited strikingly increasing trends (temperature, salinity, primary production indices) with values started exceeding the global historical means during late 1980s-early 1990s. It is suggested that the biological system exhibited a discontinuous response to CC, with two apparently climate-induced regime shifts occurring in the past 25 years. There is evidence for two fold bifurcations and four tipping points in the system, forming a folded stability landscape with three basins of attraction. The shape of the stability landscape for the Aegean Sea’s biological system suggests that while the initial state (1966-1991) was rather resilient to CC, absorbing two environmental step-changes, this was not the case for the two subsequent ones (intermediate: 1992-2002; recent: 2003-2016). Given the current trajectory of environmental change, it is highly unlikely that the biological system will ever return to its pre-1990s state, as it is entering areas of unprecedented climatic conditions and there is some evidence that the system may be even shifting towards a new state. Our approach and findings may be relevant to other marine areas of the Mediterranean and beyond, undergoing climate-driven regime shifts, and can assist to their adaptive management.

Aims: To evaluate the efficacy, effectiveness, and safety of integrase inhibitors in the treatment of HIV/AIDS in patients coinfected with tuberculosis (TB). Methods: Clinical trials or observational studies were included. The searches were performed in the MEDLINE, EMBASE, LILACS, COCHRANE, Web of Science, Scopus, and CINAHL databases using the terms “HIV”, “AIDS”, “tuberculosis”, “raltegravir potassium”, “dolutegravir”, “elvitegravir”, “bictegravir”, “integrase inhibitor”, and their respective synonyms. The methodological quality of the studies was independently assessed using the Cochrane risk of bias and Newcastle Ottawa scales. Results: Reports from three randomised clinical trials and a historical cohort were included. Patients coinfected with TB and HIV/AIDS showed a good response to TB treatment, which was above 85% in all arms of the evaluated studies. As a primary outcome, the HIV viral load suppression rates at week 48 were greater than 60% in all arms. The therapies evaluated in patients coinfected with TB and HIV/AIDS were also proven to be safe. However, there was no statistically significant difference in the efficacy outcomes between the efavirenz and integrase inhibitor arms, and regarding safety outcomes, there were few events compared with the total. Furthermore, the certainty of the evidence of the outcomes assessed was low, indicating that future research is likely to have an important impact on this estimate. Conclusion: Integrase inhibitors are effective and well tolerated, being an alternative to efavirenz in clinical protocols. However, more studies with high quality evidence are needed on the use of this treatment in health systems.

Interoceanic canals can facilitate biological invasions as they connect the world’s oceans and dissolve dispersal barriers between bioregions. As a consequence, multiple opportunities for biotic exchange arise and the resulting establishment of migrant species often causes adverse ecological and economic impacts. The Panama Canal is a key region for biotic exchange as it connects the Pacific and Atlantic Oceans in Central America. In this study, we used two complementary methods (environmental DNA (eDNA) and gillnetting) to survey fish communities in this unique waterway. Using COI (cytochrome oxidase subunit I) metabarcoding, we detected a total of 142 taxa, including evidence for the presence of sixteen Atlantic and eight Pacific marine fish inside different sections of the Canal. Of these, ten are potentially new records of marine taxa detected in the freshwater segment of the Canal. Molecular data did not capture all species caught with gillnets, but generally provided a more complete image of the fish fauna. Diversity indices based on eDNA surveys revealed significant differences across different sections of the Canal reflecting in part the prevailing environmental conditions. The observed increase in the presence of marine fish species in the Canal indicates a growing potential for interoceanic exchange of fishes across the Isthmus. Monitoring using eDNA is a rapid and efficient way to assess potential changes in the fishes of this important waterway.

Introduction: Pulmonary agenesis is a complete absence of the pulmonary parenchyma, bronchi beyond the bifurcation, and pulmonary vasculature unilaterally or bilaterally. Because of the rare occurrence, its pathophysiology and outcome remain elusive. We evaluate the clinical features and risk factors for mortality due to pulmonary agenesis. Methods: Two patients we experienced are presented as index cases. All reported cases of pulmonary agenesis were collected from online and publication databases between 1955 and 2020. We assessed the impact of comorbidity and intervention on the survival outcome. Results: We identified 230 patients—138 (60%) with right-sided, and 14 (6%) with bilateral agenesis—among 164 articles and our cases. There were 93 (40%) cardiovascular, 70 (30%) skeletal, and 48 (21%) gastrointestinal anomalies; 47 (20%) tracheal stenoses; and 33 (14%) genitourinary anomalies. Fifty-two (23%) patients had isolated pulmonary agenesis. The 2-year overall survival (OS) rate was 66% and there was no subsequent death until 13 years of age. The right agenesis was significantly associated with a lower 2-year OS rate (58% vs. 78%, p=0.019) or more frequent tracheal stenosis (28% vs. 12%, p=0.006) than left-sided disease. A multivariable analysis indicated that tracheal stenosis (hazard ratio [HR] 2.4, 95% confidence interval [CI] 1.5-4.1, p=0.004) and gastrointestinal anomaly (HR 1.9, 95% CI 1.1-3.3, p=0.018) were prognostic factors for mortality. Conclusions: The poor prognostic factors were tracheal stenosis, right agenesis and gastrointestinal anomaly. Tracheal and gastrointestinal controls are targeted at birth and in infancy for the improved survival of unilateral pulmonary agenesis.

Physics is beautiful & amazing. This paper contains 17 easy-to-read essays on modern physics over various aspects that can easily manifest a curiosity in the young minds. Essays are there without any math which entails for a easier read. They are, Complexity of Physical Law In Unification, Levitation Using Superconductivity, Cryogenics, Nuclear Energies, Speed of The Sound, To Travel In Time Is To Travel In Space, Restricted 3-Body Problem of Mechanics, Sonoluminescence, Acoustic Levitation, Evolution & Physics, 11-Dimensional Super-Gravity, Black Hole Titbits, Frequency & Wavelength (Å), Investigating The Possible shapes Of The Universe, Chaos & Unpredictability, Cat’s Schrodinger, Isoperimetric Inequality.

COVID-19 patients are prone to co-infections during their hospitalization. These co-infections are challenging as they involve longer hospital stays, high costs, and higher mortality risk. Here we present a case of a patient with multi-infection by resistant parasites, fungi, and bacteria during his hospitalization in a Peruvian hospital

Host switching allows parasites to expand their niches. However, successful switching may require suites of adaptations and also may decrease performance on the old host. As a result, reductions in gene flow accompany many host switches, driving speciation. Because host switches tend to be rapid, it is difficult to study their demographic parameters in real-time. Fundamental factors that control subsequent parasite evolution, such as the size of the switching population or the extent of immigration from the original host, remain largely unknown. To shed light on the host switching process, we explored the history of independent switches by two ectoparasitic honey bee mites (Varroa destructor and V. jacobsoni). Both switched to the western honey bee (Apis mellifera) after it was brought into contact with their ancestral host (Apis cerana), ~70 and ~12 years ago, respectively. Varroa destructor subsequently caused worldwide collapses of honey bee populations. Using whole-genome sequencing on 63 mites collected in their native ranges from both the ancestral and novel hosts, we were able to reconstruct the known temporal dynamics of the switch. We further found multiple previously undiscovered mitochondrial lineages on the novel host, along with the genetic equivalent of tens of individuals that were involved in the initial host switch. Despite being greatly reduced, some gene flow remains between mites adapted to different hosts. Our findings suggest that while reproductive isolation may facilitate the fixation of traits beneficial for exploitation of the new host, ongoing genetic exchange may allow genetic amelioration of inbreeding effects.

Half and half nail or Lindsay's nail is a rare clinical finding that can be seen in many chronic diseases, such as chronic renal failure. We report 2 cases of half and half nail aspect during severe Covid-19 infection suggesting that it can be considered as a severity marker.

Foot-and-mouth disease (FMD) is widely distributed in Sudan where outbreaks occur on an annual basis especially during the winter months (December-February). This study aimed to increase our understanding of the epidemiological patterns of FMD in Sudan and connections to neighbouring countries by characterising the genetic sequences of FMD viruses (FMDV) collected from seven Sudanese states over a 10-year period (between 2009 and 2018). FMDV was detected in 91 of the 265 samples using an antigen-detection ELISA. Three serotypes were detected: O (46.2%), A (34.1%), and SAT 2 (19.8%). Fifty-three of these samples were submitted for sequence analyses, generating sequences that were characterised as belonging to O/EA-3 (n=18), A/AFRICA/G-IV (n=23) and SAT 2/VII/Alx-12 (n=12) viral lineages. Phylogenetic analyses provided evidence that FMDV lineages were maintained within Sudan, and also highlighted epidemiological connections to FMD outbreaks reported in neighbouring countries in East and North Africa (such as Ethiopia and Egypt). This study motivates continued FMD surveillance in Sudan to monitor the circulating viral lineages and broader initiatives to improve our understanding of the epidemiological risks in the region.

Comment: Time itself being the temporal dimensions can be manipulated by means of clever physics so as to make a time travelling domain in the backyard of your own garden. The principles of this are introduced along with physics, so as to capture the beauty of time travelling on a grander scale by some arbitrarily modified civilizations in the faraway futures. This starts with the basic notions on the perspectives of time with regards to its implications in the physics of the time travel.

The Digital Imaging and Vision Applications in Science (DIVAS) program was built to improve the computational self-efficacy and skill of first- and second-year college students majoring in biological and chemical sciences. Our three-year pilot study showed that the program could be successful in both fronts. The scholars, faculty, and staff who participated formed a community of practice that became the heart of the DIVAS program. Through this community, we expanded access to the image processing workshop in collaboration with The Carpentries, supported faculty and secondary educators in developing computing modules for their classrooms, and created and staffed a "writing center for computing" on the host campus. Overall, the DIVAS program has sparked a local computing culture. DIVAS interventions and resources are freely available for adoption by other institutions. We hope to grow the community in a way that builds student access and opportunities and supports educators in the process.

Fertility preservation for women with ovarian endometriosis: it is time to adopt it as routine practice

This article aims to investigate the numerical study of electroosmotic flow of the Eyring Powell fluid under the peristaltic mechanism with the influence of the porous medium in the micro-channel. The modified system is applied externally to an electrical field in the horizontal direction and to a magnetic field in the transverse direction. The flow of nanofluids is considered in the computation. The governing equations in the nano-fluid flow are modulated. Influence of lubrication theory approximation longequations are shortened. Reduced coupled nonlinear partial differential equations like velocity and energy equations are numerically solved using the powerful and well-known mathematical software MATHEMATICA by built in NDSolve command. The influence of various important parameters on the velocity and temperature profile is summarised by graphs.

Lo spazio urbano, forma complessa di rappresentazione socio-culturale, esprime il tempo incarnato della storia umana. Il presente saggio si propone di ricucire gli edifici sacri ed il loro passato alla realtà del territorio, che per secoli ne hanno determinato forme e modalità di sviluppo. In questo processo si colloca la Congregazione Verginiana, fondata nel XII secolo secondo i dettami di San Guglielmo da Vercelli. Partendo dall'abbazia benedettina di Montevergine è stato creato un itinerario storico religioso, "Sul cammino dei Padri Verginiani", elaborando il materiale rinvenuto attraverso un accurato studio archivistico-bibliografico, sitografico e di atti presenti presso gli uffici tecnici comunali. Dalla disamina sopra cennata è emersa l'esistenza di 163 insediamenti Verginiani, tre dei quali non individuabili geograficamente. Gli edifici sono stati mappati ed inseriti in un database opportunamente strutturato in ambiente GIS, una metodologia sperimentale efficace tanto alla divulgazione in chiave turistica che, per supportare politiche di sviluppo delle aree in cui gli itinerari si materializzano. La conoscenza dell'architettura, delle tecniche costruttive ed il rapporto tra questi edifici e l'ambiente circostante siano indispensabili per adeguati interventi di valorizzazione, recupero e riqualificazione.

INTRODUCTION The fungal seed born disease popularly known as Karnal bunt is generally expressed as a cool winter/spring weather disease in the North. The weather conditions during the susceptible period are critical factors in bunt development. An average temperature range of 18 °C to 22 °C, coupled with high relative humidity (morning) or the day relative humidity, is considered optimum for infection. In the study of various diseases, it appearance in or over the crops, plants, trees and its economical product parts or grains of the crops i.e. wheat, field crops and other which were influenced by the weather condition along with the crucial parameters. The weather fluctuation and variability and environment condition will be play the very crucial role to create the optimum favourable condition and resulted to cause the infestation. Long term weather parameters were analyzed i.e. temperature, relative humidity, radiation and rainfall from 1st to 12th standard meteorological weeks but 6th to 12 SMWs are favored to development of the grain infestation disease. Workneh et al. (2007) studied the weather variables (temperature and rainfall amount and frequency) were collected and used as predictors in discriminant analysis for classifying bunt positive and -negative fields using incidence data for 1997 and 2000 to 2003 in San Saba County. Due to western disturbance in the North West part of the country were received the periodically rainfall to maintained the high level of relative humidity (Singh et al ., 2018). The higher level of relative humidity that can be maintained the higher humidity within the crop canopy and favored the fungal growth might be due to the increasing leaf or canopy wetting period. The momentum within the crop canopy will be reduced so higher level of humidity will be maintained. The simple linear regression model showed that the maximum temperature and morning relative humidity had maximum influence on the development of leafhopper population. The stepwise linear regression model was explained the coefficient of determination (R²) of leafhopper population with the range 40 to 90 per cent in respective year (Janu et al.,2018). sStansbury and McKirdy (2002) reported that there was a strong correlation (r :0.83) between the Humid Thermal Index (HTI) model, which used long-term, average-monthly data, and the rainfall model, which was based on the per cent chance of at least three Suitable Rain Events (SRE) during the susceptible period (August to October). Results suggest that northern wheat growing areas are too hot and dry (HTI<2.2, chance of SRE 15–27%), southern areas are marginal to too cold and/or wet (HTI > 3, chance of SRE 68–97%), eastern areas are marginal to too hot and dry (HTI around 2.2, chance of SRE 24–50%), and western areas are suitable (HTI between 2.2 and 3.3, chance of SRE 41–78%).

INTRODUCTIONThe 2018 Cape Town Declaration identifies the activities of the tobacco industry as incompatible with the human right to health1. The Global Burden of Disease Study estimates the annual global death toll from smoking to be 8.71 million2. Through the cultivation, production, processing and disposal of its products, the industry creates a substantial burden on the environment, which falls mainly in low and middle-income countries3. Tobacco multinationals stand condemned as a major obstacle to the achievement of the UN’s sustainable development goals4.Based on its market share of at least 12% of cigarettes sold worldwide, (https://tobaccotactics.org/wiki/philip-morris-international/), Philip Morris International (PMI) kills more than a million people per year. PMI’s bid to take over Vectura, an inhaler company whose products are used extensively by people with COPD and asthma, conditions caused and aggravated by its products, is therefore a cause for concern. A range of consequences follow from such a takeover. Vectura, its employees, and anyone continuing to work for or collaborate withVectura, become excluded from membership of respiratory professional societies as well as collaboration with academic institutions, on grants and from publication in medical journals5,6. The details of these policies vary, but as an example, the European Respiratory Society excludes anyone with tobacco industry links in the last 10 years. Many Vectura scientists will choose to leave rather than face long-term pariah status. Policies that exclude the tobacco industry from interaction with government (Article 5.3 of the WHO’s Framework Convention on Tobacco Control) would also apply to Vectura.Vectura currently receives income from the sale of a range of inhalers currently in widespread use. If a takeover by PMI goes ahead, The European Respiratory Society states that “health professionals will avoid prescribing drugs from any company that enriches the tobacco industry due to the ethical implications”.5 Patients with lung disease are also likely to be reluctant to use tobacco industry linked devices.We discuss the ethical issues raised around choice of medication in this context, and present potential alternative medications for clinicians, commissioners and patients considering switching.

The impoundment of dams can significantly alter shorelines, hydrological regime, sediment and nutrient cycle. With the completion of Chushandian reservoir dam, land use types around the reservoir have been profoundly affected by flooding. As yet, the characteristics of soil properties on different land use types in new built reservoir have not been fully elaborated. In this work, we investigated the variation of soil physical and chemical properties at distance scale for different land use types after short-term inundating. Soil physical properties, chemical properties, soil particle structure were determined. This study reported that short-term inundating had impacts on soil physical and chemical properties of different land use types. Our results indicated that the soil physical and chemical properties at 0 m site of each land use types may be mainly affected by the nutrient status of overlying water. The soil TN, TC of all land use types decreased gradually with the increase of distance from river bank, among which the contents of TN and TC at W2 were significantly higher than those at other sites. Compared with woodland, both abandoned cropland and grass land showed the phenomenon of soil particle loss and nutrient leaching. The characteristics of low NH4-N and high NO3-N were observed in the woodland after flooding, which may be related to denitrification. The main influencing factor is soil microbial activity at W20. The main influencing factor is soil nutrient status At W2. And at abandoned cropland and grassland, the main influencing factor is soil physical properties. The response of different land use types to short-term flooding may be mainly related to the degree of vegetation coverage. Abandoned cropland showed stronger resilience, while grassland showed stronger tolerance. The present study suggested that early and timing restoration will be an effective way to repair the riparian habitat.

Cancer, one of the leading causes of death worldwide, derives from an uncontrolled division of abnormal cells in a given part of the body. Targeted immunotherapy is a promising avenue of cancer treatments, galvanizing the body's own immune system to marshal B and T cells against abnormal cell growth, pathologically inhibiting antigen function and proliferation. In the current landscape of cancer immunotherapy, however, medicine industries are belabored with the need to use painstaking trial and error and numerous wet-lab investigations to test amino acid sequences' affinities to cancer antigens. Furthermore, most cancer antigens and the structures of their epitopes are unknown, and although most malignancies can be cured when diagnosed early, organ-specific assessments cannot be used for early-stage cancers. To bridge this gap, I innovate a deep convolutional neural network (CNN) model pipeline, which analyzes the complex amino acid makeup of tumor infiltrating B/T cell receptors based on the relationships of biochemical properties among adjacent amino acids predictive of how these receptor polypeptides fold in three-dimensional space, computing high affinity amino acid sequences to revolutionize both targeted drug discovery and early diagnosis.

Keywords:   food allergens; sensitization routes; allergic rhinitis; asthma; food allergy The full names of authors :(1) Vladimir V. KLIMOV1, PhD, ScD, MD, Prof., e-mail: klimov@mail.tomsknet.ru;ORCID iD 0000-0001-6673-7556;(2) Andrew V. KLIMOV1,2, PhD, MD, Assoc. Prof., e-mail: klimov.lor@mail.ru;ORCID iD 0000-0002-2776-5834.The author’s institutional affiliations :1 Immunology & Allergy Department, Siberian State Medical University, 2 Moscowsky tr, Tomsk, 634050, Russia;2 ENT Department, Siberian State Medical University, 2 Moscowsky tr, Tomsk, 634050, Russia.Author for correspondence: Vladimir V. KLIMOV, postal address: 28 Vershinin Str, Ap. 5, Tomsk, 634041, Russia; e-mail: klimov@mail.tomsknet.ru

In this study, via the Bernoulli sub-equation, the analytical traveling wave solution of the (2+1)-dimensional resonant Davey-Stewartson system is investigated. In the beginning, Based on the Riemann-Liouville fractional derivative, the time-fractional imaginary (2+1)-dimensional resonant Davey-Stewatson equation by using travelling wave is changed into a nonlinear differential system. The homogeneous balance method between the highest power terms and the highest derivative of the ordinary differential equation is authorized on the resultant outcome equation, and finally, the ordinary differential equations are solved to obtain some new exact solutions. Different cases, as well as different values of physical constants to investigate the optical soliton solutions of the resulting system, are used. The outcomes results of this study are shown in 3D dimensions graphically via Wolfram Mathematica Package.