Certolizumab

Certolizumab is a Fab fragment of a humanized monoclonal antibody against tumor necrosis factor-alpha (TNF-alpha). Differing from the other TNF-alpha inhibitors due to the absence of Fc fragment and pegylation, it binds to both the soluble and transmembrane forms of TNF-alpha, creating a strong TNF-alpha blockage. Previously approved for psoriatic arthritis, certolizumab received another approval from FDA in 2018 for the treatment of moderate to severe chronic plaque psoriasis that does not respond to conventional systemic treatments or for which these treatments are contraindicated. Administered via subcutaneous injections, certolizumab also has a low-dose option for patients weighing less than 90 kg. Certolizumab is considered a safe biological drug that can be preferred during pregnancy and lactation.Copyright © 2022 by Turkish Society of Dermatology and Venereology.

The SARS-CoV-2 Antibody and Drug Research Based on the Structure of the Spike Protein and the Mechanism of Cell Entry.

COVID-19 is a severe acute respiratory syndrome caused by a novel coronavirus, SARS-CoV- 2.COVID-19 is now a pandemic, and is not yet fully under control.As the surface spike protein (S) mediates the recognition between the virus and cell membrane and the process of cell entry, it plays an important role in the course of disease transmission.The study on the S protein not only elucidates the structure and function of virus-related proteins and explains their cellular entry mechanism, but also provides valuable information for the prevention, diagnosis and treatment of COVII)-19.Concentrated on the S protein of SARS-CoV-2, this review covers four aspects: (1 ) The structure of the S protein and its binding with angiotensin converting enzyme II (ACE2) , the specific receptor of SARS-CoV-2, is introduced in detail.Compared with SARS-CoV, the receptor binding domain (RBD) of the SARS-CoV- 2 S protein has a higher affinity with ACE2, while the affinity of the entire S protein is on the contrary.(2) Currently, the cell entry mechanism of SARS-CoV-2 meditated by the S protein is proposed to include endosomal and non-endosomal pathways.With the recognition and binding between the S protein and ACE2 or after cell entry, transmembrane protease serine 2(TMPRSS2) , lysosomal cathepsin or the furin enzyme can cleave S protein at S1/S2 cleavage site, facilitating the fusion between the virus and target membrane.(3) For the progress in SARS-CoV-2 S protein antibodies, a collection of significant antibodies are introduced and compared in the fields of the target, source and type.(4) Mechanisms of therapeutic treatments for SARS-CoV-2 varied.Though the antibody and medicine treatments related to the SARS-CoV-2 S protein are of high specificity and great efficacy, the mechanism, safety, applicability and stability of some agents are still unclear and need further assessment.Therefore, to curb the pandemic, researchers in all fields need more cooperation in the development of SARS-CoV-2 antibodies and medicines to face the great challenge.Copyright © Palaeogeography (Chinese Edition).All right reserved.

Getting Students to (and Through) Advanced Math: Where Course Offerings and Content Are Not Adding Up. American Educator Panels. Research Report. RR-A827-10

This report uses Spring 2022 data from nationally representative surveys of principals and math teachers in kindergarten through grade 12 (K-12) to explore students' opportunities to prepare for and take advanced math. The authors found that small high schools, high schools in rural areas, and high schools that predominantly serve students from historically marginalized communities tend to offer fewer advanced math courses (e.g., precalculus, Advanced Placement math courses) and that uneven access to advanced math begins in middle school. K-12 teachers who work in schools that predominately serve students living in poverty are more likely to report skipping standards-aligned content and replacing the skipped content with concepts from previous grade levels. Also, more than half of K-12 math teachers said they need additional support for delivering high-quality math instruction, especially teachers who work in schools that serve predominantly high-poverty students. In the wake of the disproportionate impacts of the COVID-19 pandemic on students living in poverty and students of color, these results highlight a critical need for resources to support teachers and to increase student access to advanced courses. [For technical information about the surveys and analysis in this report, see "Learn Together Surveys. 2022 Technical Documentation and Survey Results. Research Report. RR-A827-9" (ED626092).]

IMPACT OF THE CORONA PANDEMIC ON THE DEMOGRAPHIC STRUCTURE IN AUSTRIA

The COVID-19 pandemic and the policy measures imposed to contain the virus affected people's health and lifestyles. Based on data available to the Federal Agency "Statistics Austria”, this paper asks about the impact of the pandemic years 2020 and 2021 (and partly beyond) on the Austrian demographics and population. It shows that mortality increased significantly during this period but varied by waves of infection also with the introduction of different policy measures (e.g., lockdowns). There are also changes in the number of births over the course of the pandemic, which can be interpreted through insecurities related to lockdowns and vaccinations. People who wanted to marry or get divorced during the pandemic years were confronted with closed offices and restrictions on holding celebrations, which is why there were significantly fewer marriages and divorces. International migration dropped significantly, especially in the spring of 2020, when European and global mobility was severely restricted, with differences between people of different nationalities. This was also reflected in the number of asylum applications filed in Austria. Migrations within Austria were strongly reduced during the first lockdown in 2020, all further lockdowns had less influence on them. However, in 2020 and 2021 there were several phases in which more people moved from urban to rural areas than before the pandemic. The number of registered secondary residences – which took on new relevance in the context of mobility restrictions and the use of home offices – also changed: overall, their number increased during the pandemic, but in many municipalities, deregistrations of seasonal workers were also noticeable. © 2022 Austrian Geographical Society. All rights reserved.

Introduction

This chapter is contextual in nature. It provides an overview of the impact of COVID-19, highlighting both the significant number of deaths caused by the pandemic as well as the economic disruption that occurred. Particular attention is paid to the role of digital technologies during the pandemic, which enabled a wide range of activities (e.g. work, education and shopping) to go online. The disruptive impact of COVID-19 is widespread and far-reaching, with the pandemic acting as a 'change agent' expanding and encouraging the greater use of digital technologies. The second half of the chapter presents summaries of the other chapters in the book. In doing so, it illustrates the scope and scale of the impact of COVID-19, the multitude of different challenges it has caused, and how these varied across different regions and contexts, as well as the diversity of reactions to the pandemic. Some of these reactions are technical in nature, while others are commercial and political. The summaries also draw attention to ongoing policy debates, the significance of which has been heightened by the pandemic. © 2023 the authors.

Fast de novo antibody structure prediction with atomic accuracy

Background: In the field of antibody engineering, an essential task is to design a novel antibody whose paratopes bind to a specific antigen with correct epitopes. Understanding antibody structure and its paratope can facilitate a mechanistic understanding of its function. Therefore, antibody structure prediction from its sequence alone has always been a highly valuable problem for de novo antibody design. AlphaFold2 (AF2), a breakthrough in the field of structural biology, provides a solution to this protein structure prediction problem by learning a deep learning model. However, the computational efficiency and undesirable prediction accuracy on antibody, especially on the complementarity-determining regions limit its applications in de novo antibody design. Method(s): To learn informative representation of antibodies, we trained a deep antibody language model (ALM) on curated sequences from observed antibody space database via a well-designed transformer model. We also developed a novel model named xTrimoABFold++ to predict antibody structure from antibody sequence only based on the pretrained ALM as well as efficient evoformers and structural modules. The model was trained end-to-end on the antibody structures in PDB by minimizing the ensemble loss of domain-specific focal loss on CDR and the frame aligned point loss. Result(s): xTrimoABFold++ outperforms AF2 and OmegaFold, HelixFold-Single with 30+% improvement on RMSD. Also, it is 151 times faster than AF2 and predicts antibody structure in atomic accuracy within 20 seconds. In recently released antibodies, for example, cemiplimab of PD1 (PDB: 7WVM) and cross-neutralizing antibody 6D6 of SARS-CoV-2 (PDB: 7EAN), the RMSD of xTrimoABFold++ are 0.344 and 0.389 respectively. Conclusion(s): To the best of our knowledge, xTrimoABFold++ achieved the state-of-the-art in antibody structure prediction. Its improvement on both accuracy and efficiency makes it a valuable tool for de novo antibody design, and could make further improvement in immuno-theory.

Farmers' willingness to stabilize the land contract relationship facing the upcoming expiry of land contracts

On the verge of the expiry of land contracts, it is theoretically and practically important to explore the willingness and motivations of farmers to stabilize the land contract relationship, with regards to protecting their land contract rights, addressing potential contradictions during the land contract extension, and maintaining the stability of contracted land. Using China Land Economic Survey Data in 2020, this paper explores the impact of differences in areas per capita of household contracted land on farmers' willingness to stabilize land contract relationship. The findings show that most farmers support the stability of land contract relationship;the smaller areas per capita of contracted land are occupied by households than the average in the village, the weaker of the farmers' willingness to stabilize the land contract relationship. The difference between the areas per capita of contracted land ownership of a household and the average in the village has a greater impact on the willingness to stabilize land contract relationship for middle-and low-income farmers, while the development of land transfer market does not increased the willingness. Affected by the COVID-19 pandemic, the land plays a more important role of employment security, which reduces farmers' willingness to stabilize the land contract relationship. Furthermore, the promotion of socialized agricultural service has also mitigated the willingness of farmers o stabilize the land contract relationship.

The Application of PageRank model in urban epidemic prevention and control

The ongoing COVID-19 epidemic has had a great impact on social activities and the economy. The usage technical analysis tools to provide a more accurate and efficient reference for epidemic control measures is of great significance. This paper analyzes the characteristics and deficiencies of the existing technical methods, such as regression model, simulation calculation, differential equation and so on. By analyzing past outbreak cases and comparing the epidemic prevention measures of different cities, we discuss the importance of early and timely prevention in controlling the epidemic, and the importance of analyzing and formulating plans in advance. We then make the key observation that the spread of the virus is related to the topology of the urban network. This paper further proposes an epidemic analysis model of the optimized PageRank model, and gives a ranking algorithm for virus transmission risk levels based on road nodes, forming a visual risk warning level map, and applies the algorithm to the epidemic analysis of Yuegezhuang area in Beijing. Finally, more in-depth research directions and suggestions for prevention and control measures are put forward. © 2023 SPIE.

Realization of Coronavirus Testing Kit Using a Combination of a Triangular Photonic Crystal (PhC) Structure and a 412 nm Laser Beam

The design of a Covid-19 testing kit is proposed in this research using a photonic crystal structure (PhC) and a violet laser beam. The basic principle of this structure relies on the phenomenon of absorbance reflectance and transmission at the signal of a 412 nm laser beam. Finally, the transmitted light energy through the PhC structure is the conclusive factor to detect the types of virus which is the function of the reflectance and absorbance. The reflected light energy is computed by plane wave expansion (PWE) whereas the absorbance of light energy is obtained through numerical computation. The notable advantages of this technique are that the virus related to Covid-19 can be recognized by observing the colour of transmitted energy through a photo energy meter. Finally, the outcomes of the research affirm that the sample could be Covid-19 if the output energy would be infrared (IR). Similarly, the sample could be a normal coronavirus, if the output energy would lie within the visible regime.

Research on Chest X-Ray Image Diagnosis of Covid-19 Based on Improved ResNet

With the outbreak of covid-19 in 2020, timely and effective diagnosis and treatment of each covid-19 patient is particularly important. This paper combines the advantages of deep learning in image recognition, takes RESNET as the basic network framework, and carries out the experiment of improving the residual structure on this basis. It is tested on the open source new coronal chest radiograph data set, and the accuracy rate is 82.3%. Through a series of experiments, the training model has the advantages of good generalization, high accuracy and fast convergence. This paper proves the feasibility of the improved residual neural network in the diagnosis of covid-19. © 2023 SPIE.

FAIR TAXATION UNDER THE GLOBAL ANTI-BASE EROSION RULES?

In 2021 the OECD launched the Global Minimum Company Tax to implement the Action 1 of the BEPS Project. This instrument has seen as a good mechanism to prevent company avoiding taxes at the global level and to stop existence of the harmful tax regimes worldwide, as well as a good mechanism to achieve fair taxation in the era of global digitalization. However, the broke-out of the COVID-19 pandemic and, consequently, the close of the national borders, then armed conflict between Russia and Ukraine, boost financial crisis and the crises in almost all social and industrial spheres at the global level. Such unwilling trend, between all, has influenced behavior of the companies and the initial optimism of the OECD and other international organizations that the global minimum company tax, at the very end, would end existence of the harmful tax regimes, tax avoidance and unfair taxation, dropped significantly. Therefore, at the very end of the 2022 and the beginning of the 2023, the OECD launched consultation document on tax certainty in the application of the Pillar Two of the global minimum tax known as a GloBE (Global Anti-Base Erosion) Model Rules. This paper deals with mentioned issue and actual problems that the application of the GLoBE rules is faced with.

Breaking the exascale barrier for the electronic structure problem in ab-initio molecular dynamics

The non-orthogonal local submatrix method applied to electronic structure–based molecular dynamics simulations is shown to exceed 1.1 EFLOP/s in FP16/FP32-mixed floating-point arithmetic when using 4400 NVIDIA A100 GPUs of the Perlmutter system. This is enabled by a modification of the original method that pushes the sustained fraction of the peak performance to about 80%. Example calculations are performed for SARS-CoV-2 spike proteins with up to 83 million atoms. [ FROM AUTHOR] Copyright of International Journal of High Performance Computing Applications is the property of Sage Publications, Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Conditional dependence structure and risk spillovers between Bitcoin and fiat currencies

This paper investigates the extreme dependence and risk spillovers between Bitcoin and the currencies of the BRICS and G7 economies. We find time-varying dependence between Bitcoin and all currencies. Moreover, when analysing risk spillovers from Bitcoin to currencies, we find that Bitcoin exercises significant power over most currencies, with the South African rand and Brazilian real holding both the highest downside and upside risk before and during the COVID-19 pandemic period, respectively. When considering risk spillovers from currencies towards Bitcoin, the Japanese yen exhibits the highest downside spillovers. Importantly, we find asymmetric spillovers between extreme upward and downward movements. • We study dependencies between Bitcoin and the currencies of the BRICS and G7 economies. • We find time-varying dependence between Bitcoin and all of the fiat currencies. • Bitcoin exercises significant power over most of the considered currencies. • We find asymmetric spillovers between extreme upward and downward movements. [ FROM AUTHOR] Copyright of Emerging Markets Review is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

The impact of Covid-19 on the capital structure in emerging economies: evidence from India

PurposeCapital structure is an important corporate financing decision, particularly for companies in emerging economies. This paper attempts to understand whether the pandemic had any significant impact on the capital structure of companies in emerging economies. India being a prominent emerging economy is an ideal candidate for the analysis.Design/methodology/approachThe study utilizes three leverage ratios in an extended market index, BSE500, for the period 2015–2021. The ratios considered are short-term leverage ratio (STLR), long-term leverage ratio (LTLR) and total leverage ratio (TLR). A dummy variable differentiates the pre-epidemic (2015–2019) and pandemic (2020–2021) period. Control variables are used to represent firm characteristics such as growth, tangibility, profit, size and liquidity. Dynamic panel data regression is employed to address endogeneity.FindingsThe findings point out that Covid-19 has had a significant, negative effect on LTLR, while the impact on STLR and TLR was insignificant. The findings indicate that companies based in a culturally risk-averse environment, such as India, would reduce the long-term debt to avoid bankruptcy in times of uncertainty.Research limitations/implicationsThe study covers the impact of the pandemic on Indian companies. Hence, generalization of the findings to global context might not be valid.Practical implicationsTo maintain economic growth in the post-crisis period, Indian policymakers should ensure accessibility to low-cost capital. The findings provide impetus to deepen the insignificant corporate bond market in India for future economic revival.Originality/valueDeveloping countries are struggling to revive the economies postpandemic. This is particularly true for Asian economies which are heavily reliant on banks for survival. This research finds evidence to utilize bond market as a source of raising capital for economic revival.

A comprehensive review on technological advances in alternate drug discovery process:Drug repurposing

The traditional de novo drug discovery is time consuming, costly and in some instances the drugs will fail to treat the disease which result in a huge loss to the organization. Drug repurposing is an alternative drug discovery process to overcome the limitations of the De novo drug discovery process. Ithelps for the identification of drugs to the rare diseases as well as in the pandemic situationwithin short span of time in a cost-effective way. The underlying principle of drug repurposing is that most of the drugs identified on a primary purpose have shown to treat other diseases also. One such example is Tocilizumab is primarily used for rheumatoid arthritis and it is repurposed to treat cancer and COVID-19. At present, nearly30% of the FDA approved drugs to treat various diseases are repurposed drugs. The drug repurposing is either drug-centric or disease centric and can be studied by using both experimental and in silico studies. The in silico repurpose drug discovery process is more efficient as it screens thousands of compounds from the diverse libraries within few days by various computational methods like Virtual screening, Docking, MD simulations,Machine Learning, Artificial Intelligence, Genome Wide Association Studies (GWAS), etc. with certain limitations.These limitationscan be addressed by effective integration of advanced technologies to identify a novel multi-purpose drug.Copyright © 2023, Association of Biotechnology and Pharmacy. All rights reserved.

Post COVID-19 changes in the structure and function of the thyroid in patients with autoimmune thyroiditis with hypothyroidism

COVID-19 is a severe immunosuppressive disease that can cause changes in the clinical course of autoimmune diseases. Autoimmune thyroiditis (AIT) is no exception. It is relevant to study the features of the clinical course of existing AIT in the post-COVID-19 period. The work aims to study the changes in the structure and function of the thyroid in patients with AIT with subclinical and manifest compensated hypothyroidism who had moderate COVID-19. A total of 123 patients aged 21-49 with AIT with subclinical hypothyroidism - 43 (group 1, 12 of whom had moderate COVID-19) and manifest hypothyroidism in the stage of medical compensation - 80 (group 2, 32 of whom had moderate COVID-19). The duration of AIT ranged from 4 to 13 years. In all cases, upon inclusion in the study and 2 and 6 months after it, changes in the structure of the thyroid gland were studied according to ultrasound data, as well as its functional capacity and the degree of compensation of hypothyroidism according to the thyroid-stimulating hormone indicator. In all patients with AIT, COVID-19 caused the progression of structural changes in the thyroid within one of two variants of the ultrasound picture of thyroiditis - hypoechoic heterogeneous or pseudo micronodular. The hormone-producing function also changed: in 7 out of 12 patients of group 1 of the main subgroup, hypothyroidism changed from subclinical to manifest hypothyroidism in the postoperative period, and in all patients of group 2 of the main subgroup, a further decrease in hormone synthesis was noted. In the post-COVID-19 period, patients with AIT undergo a progression of structural changes in the thyroid gland and a decrease in the synthesis of thyroid hormones.Copyright © 2023 The Authors.

Novel Degree-Based Topological Descriptors of Fenofibrate Using M-Polynomial

Chemical graph theory is currently expanding the use of topological indices to numerically encode chemical structure. The prediction of the characteristics provided by the chemical structure of the molecule is a key feature of these topological indices. The concepts from graph theory are presented in a brief discussion of one of its many applications to chemistry, namely, the use of topological indices in quantitative structure-activity relationship (QSAR) studies and quantitative structure-property relationship (QSPR) studies. This study uses the M-polynomial approach, a newly discovered technique, to determine the topological indices of the medication fenofibrate. With the use of degree-based topological indices, we additionally construct a few novel degree based topological descriptors of fenofibrate structure using M-polynomial. When using M-polynomials in place of degree-based indices, the computation of the topological indices can be completed relatively quickly. The topological indices are also plotted. Using M-polynomial, we compute novel formulas for the modified first Zagreb index, modified second Zagreb index, first and second hyper Zagreb indices, SK index, SK1 index, SK2 index, modified Albertson index, redefined first Zagreb index, and degree-based topological indices.

Evaluation of regional features of electronic commerce in Europe

The subject of the study in the article is the e-commerce market in Europe. The aim of the article is to analyze the regional features of e-commerce in Europe using the main development indicators of e-commerce. The paper uses the method of desktop research, i.e. the analysis of available data, which is to obtain and study information that is already in the form of reports, statistics and research. In addition, the impact of COVID-19 on the development of e-commerce in Europe was presented. © 2022 - IOS Press. All rights reserved.

DEATH LANDSCAPES AND COVID-19 IN THE AMERICAS: NORMATIVE RESPONSES OF THE INTER-AMERICAN COMMISSION OF HUMAN RIGHTS TOWARDS VULNERABILITY-DEATH

The article engages with the death landscapes of the Americas' two largest democracies – Brazil and the United States – during the Covid-19 crisis, offering a conceptual tool entitled vulnerability-death binomial to consider the extent to which a politics of tragedy is a turning point in the ways institutional politics addresses vulnerability and death, emphasizing the work of the Inter-American Commission on Human Rights (IACHR). When analyzing the normative responses of IACHR, no articulation was found between vulnerability and death but, instead, a bifurcation of each. Although it reveals that there is not a normative interplay between vulnerability and death, the bifurcation does not mean a choice between binary paths. While the two democracies have raised institutional challenges, the IACHR deepened certain senses of vulnerability and a normative movement towards death: issues historically absent from the international basic structure and capable of challenging the international justice theory © 2023, Lua Nova.All Rights Reserved.

Primary immunodeficiency associated with a SAMD9L mutation

Background: SAMD9L is a tumor suppressor involved in regulating the proliferation and maturation of cells, particularly those derived from the bone marrow, and appears to play an important role in cerebellar function. It can be activated in hematopoietic stem cells by type I and type II interferons. It has been hypothesized to act as a critical antiviral gatekeeper regulating interferon dependent demand driven hematopoiesis. Gain of function mutations can present with an immunodeficiency due to transient severe cytopenias during viral infection. Case presentation: We report a 3-year-old boy born full term with a history of severe thrombocytopenia requiring transfusions, developmental delay, ataxia, seizure disorder, and recurrent severe respiratory viral infections. His infectious history was significant for respiratory syncytial virus with shock requiring extracorporeal membrane oxygenation complicated by cerebral infarction and a group A streptococcus empyema, osteomyelitis requiring a left below the knee amputation, and infections with rhinovirus, COVID-19, and parainfluenza requiring hospitalizations for respiratory support. Initial immunologic evaluation was done during his hospitalization for parainfluenza. His full T cell subsets was significant for lymphopenia across all cell lines with CD3 934/microL, CD4 653/microL, CD8 227/microL, CD19 76/microL, and CD1656 61/microL. His mitogen stimulation assay to phytohemagglutinin and pokeweed was normal. Immunoglobulin panel showed a mildly decreased IgM of 25 mg/dL, but normal IgA and IgG. Vaccine titers demonstrated protective titers to 12/22 pneumococcus serotypes, varicella, diphtheria, mumps, rubella, and rubeola. Repeat full T cell subsets 6 weeks later revealed marked improvement in lymphocyte counts with CD3 3083/microL, CD4 2101/microL, CD8 839/microL, CD19 225/microL, and CD1656/microL. A primary immunodeficiency genetic panel was ordered and positive for a heterozygous SAMD9L c.1549T>C (p.Trp517Arg) mutation classified as a variant of unknown significance. Discussion(s): This patient's history of severe viral infections, ataxia, thrombocytopenia, and severe transient lymphopenia during infection is suggestive of a SAM9DL gain of function mutation. Protein modeling done by the laboratory suggests this missense mutation would affect protein structure. The mutation found has been observed in individuals with thrombocytopenia. This case highlights the importance of immunophenotyping both during acute illness and once recovered.Copyright © 2023 Elsevier Inc.