Application Of Rules Research Articles

Identification of RdRp-NiRAN/JAK1 Dual-Target Drugs for COVID-19 Treatment.

Inhibition of virus replication and inflammatory response is important for the treatment of severe COVID-19 patients. RNA-dependent RNA polymerase (RdRp) is indispensable for SARS-CoV-2 replication, and Janus kinase (JAK) 1 inhibitors exert immunosuppressive effects. RdRp/JAK1 dual-target drugs are expected to ameliorate the severity of the COVID-19 disease. The N-terminal nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain of RdRp is a pseudokinase, and it has structural similarities with JAK1. Herein, we evaluated the inhibitory effects of triphosphate forms of 31 nucleoside drugs in the DrugBank database on the NiRAN domain and JAK1 through a combination of theoretical and experimental methods. By analyzing the three properties of 31 nucleoside drugs (total hydrophobic surface area, number of hydrophobic atoms, and molecular weight), these drugs met the application rule of our developed molecular docking with conformer-dependent charges (MDCC). Based on the MDCC method combined with molecular dynamics simulations, Azvudine and Citicoline among these 31 drugs showed stronger predicted binding affinities with the NiRAN domain as well as JAK1 compared to the reference drug Remdesivir. Further experimental verification, including a thermal shift assay and homogeneous time-resolved fluorescence assay, demonstrated that Azvudine was an RdRp-NiRAN/JAK1 dual-target drug. This work provided a previously unexplored mechanism of Azvudine for COVID-19 treatment and proposed a design concept for RdRp-NiRAN/JAK1 dual-target nucleoside drugs.

A Novel Sensitivity Maximization at a Given Specificity Method for Binary Classifications

Abstract In the cancer early detection field, logistic regression is a frequently used approach to establish a combination rule that differentiates cancer from non-cancer. However, the application of logistic regression relies on a maximum likelihood approach, which may not yield optimal combination rules for maximizing sensitivity at a clinically desirable specificity and vice versa. Here, we have developed an improved regression framework, Sensitivity Maximization At a Given Specificity, SMAGS, for binary classification that finds the linear decision rule yielding the maximum sensitivity for a given specificity or the maximum specificity for a given sensitivity. We additionally expand the framework for feature selection that satisfies sensitivity and specificity maximizations. We compare our SMAGS method with normal logistic regression using two synthetic datasets and reported data for colorectal cancer (CRC) from the 2018 CancerSEEK study. In the CRC CancerSEEK dataset, we report 14% improvement in sensitivity at 98.5% specificity (0.31 vs 0.57; p-value:<0.05). The SMAGS method provides an alternative to logistic regression for modeling combination rules for biomarkers and early detection applications.

Rukun Kematian Dalam Pertukaran dan Sanksi (Studi Kasus di Desa Hadungdung, Kecamatan Portibi, Kabupaten Padang Lawas Utara)

The pillar of death is a community tradition in Hadungdung Village which is carried out to ease the burden on families who are experiencing misfortune due to the death of one of their family members. The pillar of death is not just a cultural tradition but in the pillar of death there is a high value of solidarity between communities. Exchange and sanctions in the pillar of death are one of the forms of practice carried out in the pillar of death in Hadungdung village. The formulation of the problem in this study is what is the meaning of the pillar of death in the community of Hadungdung village, how the exchange is practiced in the pillar of death in Hadungdung village and how sanctions are practiced on members of the pillar of death in Hadungdung village. The informants of this study amounted to 6 (six) people, namely the chairman of the death pillar and members of the death pillar, in determining the research informants, the researcher used the purposive technique. Data collection was carried out using observation, interview and documentation methods. The results of the study show that the pillar of death for the people of Hadungdung village as a form of help, the exchange system carried out in the pillar of death is not just in the form of labor and material assistance, people who come to condole and help will get a packet of rice and side dishes as a sign of gratitude. Clear and firm sanctions in the pillar of death make the members of the pillar of death more responsible and obedient to the applicable rules.

Family member experience with restricted family presence in Canadian PICUs: an interpretive descriptive study

PurposeWe performed this study to explore family member experiences with restrictions to family presence during their child’s PICU admission, leveraging the unique context of the COVID-19 pandemic to aid in future ethical and informed decision-making.MethodsQualitative interpretive descriptive study with family members of Canadian PICU patients admitted from March 2020 to April 2021 who experienced restricted family presence (RFP) policies. Respondents were purposively sampled for demographic-based maximum variation.We generated themes through inductive thematic analysis of open-ended interviews.ResultsFourteen parental figures from five regions across Canada participated. We identified four themes associated with the lived experience and impact of the restrictions on family members of critically ill children: (1) challenges to fulfilling the parent role, (2) isolation from primary supports during a time of crisis, (3) navigating increased logistical difficulties, and (4) seeking compassionate approaches within the healthcare system.Conclusion: RFP policies created a range of barriers for family members of critically ill children. Healthcare organizations and teams may play a role in removing barriers through consistent and empathetic application of rules with consideration for the duality of the parent role in PICUs, providing important post-pandemic policy and practice implications.What is known:• Parental presence with critically ill children may improve health outcomes for patients and their families.• Restrictions to family presence in PICUs continue to occur internationally and, during COVID-19, resulted in parental isolation, anxiety, and increased stress. What is new:• By isolating family members and removing supports, COVID-19-related restrictions in Canadian PICUs challenged family members’ ability to fulfil their parent roles while meeting their own needs. • Families need empathetic, advocacy-based approaches from clinicians and healthcare systems to maintain trust and therapeutic relationships in a family-centered organization.

Conceptual framework for data harmonisation in mental health using the International Classification of Functioning, Disability and Health: an example with the R2D2-MH consortium

IntroductionAdvancing research and support for neurologically diverse populations requires novel data harmonisation methods that are capable of aligning with contemporary approaches to understanding health and disability.ObjectivesWe present the International Classification...

Stylus Romanae curiae in Historical and Positive Canon Law

Stylus Romanae Curiae, as an important element influencing, guiding and supplementing the application of the rules of canon law in practice, originally developed from the collections of forms and rules of the Apostolic Office. The popes initially wished that the central administrative and judicial bodies, designed in a centralist manner and established by them, not only exercised control over the application of universal rules, but also supplemented them and acted as a guide to jurisprudence. Thus, the Stylus Romanae Curiae began to influence not only the further development of canon-law science, but also legal practice in a significant manner, which occurred mainly when filling gaps in the law, but also when interpreting and deciding recurring types of cases in terms of administrative instructions or judicial precedents. However, recognition of the value of the source of law by several canonists made it an undesirable element over time, which the papacy managed to eliminate only at the beginning of the 20th century. The main goal of the study is to point out the conceptual definition and practical functioning of the Stylus Romanae Curiae in history and the gradual weakening of its position in the codified law of the Catholic Church, which culminated in the positive law.

Investigation of cross-association behavior in water-ethanol solutions: A combined computational-ATR spectroscopy study.

The water/ethanol system possesses complexities at the molecular level, which render its description a difficult task. For the elucidation of the system's hydrogen bonding features that are the key factors in its complex behavior, we conduct a Density Functional Theory analysis on relevant water/ethanol clusters inside implicit solvent cavities for the determination of the ethanol donor hydrogen bond strength. We record Attenuated Total Reflectance spectra of water/ethanol-OD solutions and utilize our density and refractive index measurements for post-processing. The application of the Badger-Bauer rule reveals a minimum in the strength of the ethanol donor hydrogen bond for a composition of xwater = 0.74. We attempt to analyze further this result by estimating the effect of the implicit solvent on the ethanol donor hydrogen bond strength, finding it to be incremental. A brief analysis of different cluster conformations is carried out to determine the cooperativity conditions that can potentially explain the observed minimum in the ethanol donor hydrogen bond strength. These observations are related to notions of microheterogeneity in water/alcohol mixtures and provide context toward a more elaborate picture of association in heteroclusters.

From single-objective to multi-objective reinforcement learning-based model transformation

AbstractModel-driven optimization allows to directly apply domain-specific modeling languages to define models which are subsequently optimized by applying a predefined set of model transformation rules. Objectives guide the optimization processes which can range from one single objective formulation resulting in one single solution to a set of objectives that necessitates the identification of a Pareto-optimal set of solutions. In recent years, a multitude of reinforcement learning approaches has been proposed that support both optimization cases and competitive results for various problem instances have been reported. However, their application to the field of model-driven optimization has not gained much attention yet, especially when compared to the extensive application of meta-heuristic search approaches such as genetic algorithms. Thus, there is a lack of knowledge about the applicability and performance of reinforcement learning for model-driven optimization. We therefore present in this paper a general framework for applying reinforcement learning to model-driven optimization problems. In particular, we show how a catalog of different reinforcement learning algorithms can be integrated with existing model-driven optimization approaches that use a transformation rule application encoding. We exemplify this integration by presenting a dedicated reinforcement learning extension for MOMoT. We build on this tool support and investigate several case studies for validating the applicability of reinforcement learning for model-driven optimization and compare the performance against a genetic algorithm. The results show clear advantages of using RL for single-objective problems, especially for cases where the transformation steps are highly dependent on each other. For multi-objective problems, the results are more diverse and case-specific, which further motivates the usage of model-driven optimization to utilize different approaches to find the best solutions.

Effect of Critical Thinking Skills on Misconceptions of Students in Learning Mathematics at the Elementary School Level

The aim of mathematics education in schools is to create logical reasoning and critical thinking ability in students. These skills development not only help students understand better but can also help remove the misconceptions they have about mathematical concepts. The purpose of this study was to investigate how critical thinking skills can help address misconceptions in mathematics learning at the elementary level. The research used an A-B-A design to determine the effects of an intervention, which is a perfect design for this purpose. 35 eighth-grade students who were enrolled in the current academic year were participants in this study. Three researcher-developed tools facilitated data collection. The first and initial tool was called the Test of Critical Thinking Skills (ToCTS), which measured students' critical thinking math skills. The second tool, the Test of Misconceptions (ToM), was developed to identify specifically how the students thought they were solving the problems. Finally, an interview protocol was used to learn about the students' reasoning regarding their answers on the tests. The mathematics curriculum of grades three to eight formed the basis of the development of these instruments, both close-ended and open-ended questions. Descriptive and inferential statistical methods were used in data analysis, and qualitative content from the interviews was applied to thematic analysis. A poor level of critical thinking skills in factoring equations and selecting proper solving methods for linear equations was shown by students. In addition, students had difficulty solving complete mathematical problems with linear equations. A significant gap was identified in their understanding and application of the BODMAS rule during algebraic operations. Based on these findings, the study recommended fostering critical thinking skills to improve students' abilities in factoring equations. Teachers should provide clear and comprehensive guidance to help students solve mathematical problems effectively. To address misconceptions, educators could introduce simplified problem-solving methods and reinforce students’ understanding of fundamental operations and rules. Specifically, it is essential to provide targeted instruction on the application of the BODMAS rule in algebraic contexts to enhance students' problem-solving capabilities.

Transfer Pricing End-of-Year Adjustments in France

Tough there are no specific provisions on year-end adjustments in French law and regulations, the application of the general transfer rules and a rather well-established practice are reasons to allow, and even recommend, to perform such adjustments where TNMM methods are applied. This article indicates how to properly perform and document such adjustments.The article is part of a special issue of the International Transfer Pricing Journal on transfer pricing end-of-year adjustments. The other articles include the General Report and contributions on Belgium, Germany, Ireland, Italy, Korea, the Netherlands, Spain, the United Kingdom and the United States.

Optimal sequential detection by sparsity likelihood

We propose here a sparsity likelihood stopping rule to detect change-points when there are multiple data streams. It is optimal in the sense of minimizing, asymptotically, the detection delay when the change-points is present in only a small fraction of the data streams. This optimality holds at all levels of change-point sparsity. A key contribution of this paper is that we show optimality when there is extreme sparsity. Extreme sparsity refers to the number of data streams with change-points increasing very slowly as the number of data streams goes to infinity. The theoretical results are backed by a numerical study that shows the sparsity likelihood stopping rule performing well at all levels of sparsity. Applications of the stopping rule on non-normal models are also illustrated here.

Kekerasan Fisik Yang Dilakukan Oleh Anggota Polri Terhadap Masyarakat

Introduction: The National Police is a public security protection agency, but now many individuals are caught committing acts that disrupt security and even persecute the community. The existence of these violations adds to the long blacklist of increased violations of discipline and code of ethics committed by members of the National Police.Purposes of the Research: To analyze physical violence committed by members of the National Police against the community, this is because the police is a subsystem that is directly related to the perpetrators of crimes and the community, so that the duties and responsibilities of the police can be said to be greater than other subsystems.Methods of the Research: The method used to analyze and discuss this problem is Normative Juridical.Results of the Research: Increased police commitment to better protection and promotion of human rights at the national level. This was realized by the birth of Law No. 39 of 1999 concerning Human Rights. As stipulated in international human rights law and standards, the police have rights, but there are also limits to the powers of the police. However, different from the expected reality, the presence of the police in the midst of the community has caused a scourge for the community. There is police behavior that deviates from the expected professional ethics and there are also those that make the community miserable, such as pungli, arrogant and violent behavior. This causes a fall in public trust in the police Regardless of whether the actions of the National Police are true or not, in the institution of the National Police if there are irregularities, violations of the law and abuse of authority, then members of the National Police will be processed based on the applicable rules.

Application of the Bruun rule in evaluating the effect of water level fall on the Caspian Sea profile evolution

ABSTRACT The combined effects of climate change and anthropogenic activities induce significant sea-level alterations, changing beach morphologies. While the effects of water level rise on coastal regions have been extensively studied, the consequences caused by water level fall, particularly in enclosed water basins, have received limited attention. The Bruun rule is an empirical approach for estimating the erosion of sandy beaches in response to sea level rise. This study evaluates the efficacy of the Bruun rule and associated methods under water-level fall conditions. An extensive investigation was followed to understand Bruun’s rule application and its hypotheses in this context. Cross-shore profiles were collected from three stations: Larim, Farahabad, and Miankaleh, located along the southeastern coast of the Caspian Sea between 2013 and 2021. Results indicate that Bruun’s predictions are more reliable, considering their accuracy and applicability. Additionally, active zone bed slope emerges as the most significant factor influencing Bruun prediction, performing well with slopes between 0.013 and 0.016. Moreover, Bruun’s hypotheses were assessed by comparing the observed profiles and water levels over 7 months, 2 years, and 3 years, revealing a lag time contradicting Bruun’s hypothesis. Results further indicate that the Bruun rule overlooks the impacts of water level fluctuations.

Charting a way forward for the use of data science in competition enforcement and platform regulation

ABSTRACT Competition authorities and other regulators already rely on data science to monitor markets and check compliance with applicable rules. The Digital Markets Act and the Digital Services Act have made the use of data science by regulators even more relevant, given the scale and complexity of the oversight required. The existing use of data science shows that regulators are able to adapt their organizations and processes to realize the potential of using technology tools in their activities. At the same time, the use of data science poses challenges in terms of data reliability and individual privacy. Beyond involvement in specific investigations, data science also has the potential to reform the work of regulators by moving towards a more proactive form of enforcement. The sharing of data science expertise and tools between regulators deserves to be further facilitated to increase collaboration and share resources in monitoring the platform economy.

Early Voter Engagement Through Smart Voting Movement RRI Makassar

General elections target novice voters as a flying vote. Novice voters are those who are eligible to participate in general elections for the first time with a minimum age of 17 years. Among them are class XII SMA/MA or new students. In the 2024 General Election, novice voters as a whole dominated the permanent voter list (DPT) with a number reaching around 56.45% of the total voters. However, the level of voter participation has decreased, due to disappointment in the results of previous elections and local elections. Various problems have resulted in a decrease in voter participation, including the tendency of pragmatic political elites who do not want to know about citizens' participation rights. In order to increase public confidence in domestic democracy, a strategy to increase political participation is needed. The development of Indonesian politics must be known to all citizens, in order to understand the correct political choices and in accordance with decisions without tendency and intimidation according to applicable rules. The research method used is descriptive qualitative method, because it explores the phenomenon in depth. The Smart Choosing Movement (GCM) is effective in increasing political awareness among first-time voters. GCM succeeded in raising awareness of the importance of elections, government functions, and rights and responsibilities as citizens. GCM is effective in increasing understanding of the electoral process, from registration to voting. The program is able to increase the motivation of novice voters to be directly involved in elections.

Pseudoentropy sum rule by analytical continuation of the superposition parameter

In this paper, we establish a sum rule that connects the pseudoentropy and entanglement entropy of the superposition state. Through analytical continuation of the superposition parameter, we demonstrate that the transition matrix and density matrix of the superposition state can be treated in a unified manner. Within this framework, we naturally derive sum rules for the (reduced) transition matrix, pseudo-Rényi entropy, and pseudoentropy. Furthermore, we demonstrate the close relationship between the sum rule for pseudoentropy and the singularity structure of the entropy function for the superposition state after analytical continuation. We also explore potential applications of the sum rule, including its relevance to understanding the gravity dual of non-Hermitian transition matrices and establishing upper bounds for the absolute value of pseudoentropy.

Enhancing Metalinguistic Awareness Through Microlearning: A Comparative Analysis of Catalan Acquisition Between Multilingual French and English Learners

Knowing that previously learned languages may influence and support language learning among multilingual learners, equipping educators with diverse tools and resources empowers them to make more informed decisions in facilitating language learning. This holds particular significance in the case of minority languages like Catalan, where resource availability tends to be more restricted. This paper presents the findings of a project aimed at identifying the specific needs of multilingual B1 learners of Catalan. Using a comprehensive five-way classification system, the study compares the written productions of multilingual learners from different linguistic backgrounds (English and French L1 learners of Catalan). Analyses revealed a similar pattern regarding the nature of the errors, with incorrect word selections at the lexical-semantic, syntactic, and orthographic levels being the most frequent. Both groups differ significantly in terms of the distribution of errors; however, they did not differ when the analyses were conducted by error types. In both cases, the most frequent error was the lexical-semantic misselections, with false analogies and incomplete applications of rules explaining the errors. These findings led to the creation of just-in-time microlearning capsules tailored to address these issues. The microlearning capsules were designed to enhance students' metalinguistic awareness. Students' and teachers' perceptions of the tool were also assessed, and both groups predominantly viewed interlinguistic information as beneficial to language learning. This project highlights how microlearning, tailored to frequent errors, can bolster multilingual learners' acquisition and provides promising tools for language teaching.

Examining the Regulatory Frameworks Governing Prohibition of Torture in Warfare

The aim of the paper is to examine the regulatory frameworks governing the prohibitions of torture in warfare to determine their adequacy in protecting civilian populations against torture during armed hostilities. To address the threat posed by torture in warfare against the civilian populations, the regulatory frameworks on International Humanitarian Law (IHL), International Human Rights Law (IHRL) and International Criminal Law (ICL) are examined. It may be argued that although this regulatory framework is aimed at guaranteeing safety of the civilian populations in situations of armed hostilities but are not capable of dealing with the current challenges. The paper employs a doctrinal approach by identifying and analyzing the applicable rules of IHL, IHRL, and ICL. It demonstrates how these laws impact the basic rights of civilian populations during armed conflicts. The paper found that despite the performance of the Tribunals as regulatory measures, they are confronted with several challenges prosecution and enforcement of their decisions. The paper concludes with recommendations that are relevant to address the challenges in order to ensure that the various frameworks are effectively implemented by States to safeguard the civilian populations from acts of torture during armed hostilities.

Excessive Pharmaceutical Pricing and Repercussions on Paediatric Health Services

Context: Paediatric pharmaceutics have a significant share in expensive drugs. Recent years have seen significant calls for intervention against high prices for pharmaceutical products. The prohibition of prices that are excessive as a form of abuse of dominance is considered as Competition law violation in the European Union Law and national legal orders of its Member States. Majority of the Organization for Economic Cooperation and Development (OECD) member countries have similar prohibitions in their respective Competition laws with important exemption of United States (US) Antirust Law, although there is some indication of change in US exactly in the area of pharmaceutical sector. Regulation of excessive prices also exists in Competition laws of all BRICS (Brazil, Russian Federation, India, China, and South Africa) countries. The problem of excessive prices in pharmaceutics is one of the emerging themes in Competition law literature and case law development. This is the area where intellectual property rights, usually patent protection, collide with competition rules. Costs of research and development for such pharmaceutics are often very high emphasizing the need for balance between colliding legitimate interests: access to health and research development. Aim: To present regulatory and case law development of application of excessive prices as form of abuse of dominance in pharmaceutical sector with emphasis on paediatric health services. Data source: OECD, PubMed, Google Scholar, Scopus. Conclusion: Balance between competition rules on excessive prices as form of abuse of dominance and intellectual property rights in the area of expensive paediatric pharmaceutics can be regarded as suboptimal. Thus, there is a need for further regulatory development and application of rules on excessive prices in that field.

Spillover Effects of the SEC's Regulatory Oversight on Private Debt Contracting: Evidence from Cross‐listed Foreign Firms

ABSTRACTWe examine the effect of the Securities and Exchange Commission's (SEC) regulatory oversight on private debt contracting outcomes, using the signing of the multilateral memorandum of understanding (MMoU) as a natural experiment. The MMoU enables the SEC to take stricter punitive actions against wealth expropriation by cross‐listed firms’ insiders and enforce better compliance with applicable rules and regulations. We find that enhanced SEC oversight in the post‐MMoU regime lowers loan spreads by 36 basis points, thus saving an average cross‐listed firm approximately $9 million in direct loan costs over the life of a bank loan. Cross‐sectional analyses show that the effect is more pronounced for borrowers from countries with weaker institutions, borrowers with greater accounting discretion, and for loans arranged by top lenders or loans not secured by collateral. Conversely, the effect is less pronounced for borrowers who use IFRS or when the SEC faces greater budgetary constraints. Enhanced SEC oversight also leads to an increase in loan maturity and a decrease in financial covenants. Our evidence suggests that while the SEC's primary mandate is to protect public equity and bond investors, its supervision yields substantial borrowing cost savings and more lenient nonprice loan terms in the private debt markets as well.