Aspects Of Validation Research Articles

Uncovering ASO-Targetable Deep Intronic AIRE Variants: Insights and Therapeutic Implications.

High-throughput DNA sequencing has accelerated the discovery of disease-causing genetic variants, yet only in 10-40% of cases yield a genetic diagnosis. Increased implementation of genome sequencing has enabled a deeper exploration of the noncoding genome and recognition of noncoding variants as major contributors to disease. In a recent study, we identified a deep intronic variant in the AutoImmune REgulator (AIRE) gene (c.1504-818 G>A) as the cause of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a life-threatening monogenic autoimmune disorder most often caused by biallelic AIRE defects. This deep intronic variant disrupts normal splicing AIRE , causing pseudoexon inclusion and altered protein function. By developing an antisense oligonucleotide (ASO) targeting the pseudoexon sequence, we restored normal AIRE transcript in vitro, thereby revealing a potential genotype-specific candidate treatment. Our study illustrates key aspects of intronic variant detection, validation, and candidate ASO development. Herein, we briefly highlight the growing potential of ASO-based therapies for deep intronic variants, addressing the unmet need of personalized, genotype-specific therapies in diseases lacking curative options.

Force versus Response: Methods for Activating and Characterizing Mechanosensitive Ion Channels and GPCRs.

Mechanotransduction is the process whereby cells convert mechanical signals into electrochemical responses, where mechanosensitive proteins mediate this interaction. To characterize these critical proteins, numerous techniques have been developed that apply forces and measure the subsequent cellular responses. While these approaches have given insight into specific aspects of many such proteins, subsequent validation and cross-comparison between techniques remain difficult given significant variations in reported activation thresholds and responses for the same protein across different studies. Accurately determining mechanosensitivity responses for various proteins, however, is essential for understanding mechanotransduction and potential physiological implications, including therapeutics. This critical review provides an assessment of current and emerging approaches used for mechanosensitive ion channel and G-Coupled Receptors (GPCRs) stimulation and measurement, with a specific focus on the ability to quantitatively measure mechanosensitive responses.

Aplikasi E-Modul Suhu dan Kalor sebagai Rancangan Bahan Ajar Fisika di SMA

Physics learning in SMA Negeri 1 Lumajang often uses textbooks rather than learning modules as learning resources, so it is necessary to develop physics e-modules. This study aims to determine the development design and the validity of physics e-modules of temperature and heat material in senior high school. The research method used is descriptive which describe phenomena or characteristics of the population under the study. The research instrument is a validation questionnaire, interview guidelines, and documentation. The data obtained were the results of validation conducted by 3 expert validators and 2 user validators. The results showed that the average value of the five validators covering four aspect of eligibility namely content, construct, language, the content feasibility aspect gets a score of 83%, the construct feasibility aspect gets a score of 83%, the language feasibility aspect gets a score of 90%, the display feasibility aspect gets a score of 86%. The overall average validation aspects of the five validators get a value of 85,8% with very valid criteria. Based on the research results obtained, it can be concluded that the physics e-module of temperature and heat material gets validity results with very valid criteria and can be tested for development to students at the research school.

Improved performance of three mirror anastigmat telescope with freeform surface: Optical design, testing and validation aspects

"In this paper, the optical design of a Three Mirror Anastigmat (TMA) Telescope is modified by substitution of a convex freeform secondary and optimization carried out to obtain improved performance. The proposed convex freeform surface is precisely manufactured using the bonnet polishing technique and tested with a sub-aperture stitched algorithm, meeting the specified surface accuracy requirements. Further, to validate the design, the realized secondary freeform optic is tested in conjunction with primary and tertiary optics in the conceived TMA configuration. The telescope system performance is established using a double-pass interferometric test setup. The modified design enhances the telescope system's performance in the extended field of view (FoV) from ±2.5° to ±3.5° across the track and from ±0.4° to ±0.6° along the track. Measured performance results demonstrate an average modulation transfer function (MTF) of 0.56 and an average Strehl ratio of 0.64 at all field points. The effective focal length of the system is computed to be 975 mm. In summary, the proposed freeform surface significantly improves the optical system performance within the available real estate of the envisaged space telescope system."

THE DEVELOPMENT OF BLENDED LEARNING-BASED DIGITAL TEACHING MATERIALS ON KINEMATICS FOR ISLAMIC PRIMARY SCHOOL PROSPECTIVE TEACHERS IN SCIENCE LEARNING

Kinematics is one of fundamental materials in Basic Science Courses for Islamic Primary Schools Prospective Teacher. Kinematics often difficult for student because it needs schematic drawings and formula for motion. Thus, the kinematics teaching materials absolutely needed for Islamic Primary Schools Prospective Teacher. The current findings suggest that the environment in which Islamic Primary Schools Prospective Teachers learn has not been conducive to their growth and development. These initial observations indicate that certain factors may be hindering their progress. Therefore, digital teaching materials are needed that can facilitate the entire science learning process. The purpose of this research is to explicate the development process, along with the validation and comprehensibility of digital science teaching materials as learning media for prospective elementary school teachers in Islamic education. The Lee and Owens development model was used in the creation of this digital teaching material. The Lee Owens developmental model consist of assessment/analysis, need assessment, front-end analysis, design, development, implementation, and evaluation. A material validation questionnaire, media, and a student readability test were used in the questionnaire with Likert scale. The subject of this research are 24 students of Islamic Primary Schools Prospective Teacher in UIN Maulana Malik Ibrahim Malang. The material aspect of product validation showed an average result of 92.08%, while the media validation aspect scored 90.90%. The readability test for digital science teaching materials obtained a score of 83.2%. These findings suggest that digital science teaching materials are highly valid and suitable for use as learning media for prospective Islamic elementary school teachers. As a result, it is possible to conclude that digital science teaching materials are extremely valid and appropriate for use as learning media for prospective Islamic elementary school teachers.

An ultra-fast green ultra-high-performance liquid chromatography-tandem mass spectrometry method for estimating the in vitro metabolic stability of zotizalkib in human liver microsomes.

Zotizalkib (ZTK, TPX-0131) is a fourth-generation highly effective inhibitor of wild-type anaplastic lymphoma kinase (ALK) and ALK-resistant mutations that can penetrate the central nervous system. It exhibited greater potency compared to all five officially approved ALK inhibitors. The aim of this study was to develop a rapid, accurate, eco-friendly, and highly sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for measuring the concentration of ZTK in human liver microsomes (HLMs). The validation aspects of the current UHPLC-MS/MS methodology in the HLMs were conducted in accordance with the bioanalytical method validation standards specified by the US Food and Drug Administration. ZTK and encorafenib were separated using an Agilent C8 column (Eclipse Plus) and an isocratic mobile phase. The calibration curve for the developed ZTK exhibited a linear relationship within the concentration range of 1-3000ng/mL. The results from the Analytical Green-ness Metric Approach program (0.76) suggested that the created method demonstrated a significant degree of environmental sustainability. The in vitro half-life (t1/2) and intrinsic clearance (Clint) of ZTK were determined to be 15.79min and 51.35mL/min/kg, respectively that suggests the ZTK exhibits characteristics similar to those of a medication with a high extraction ratio. These approaches are crucial for the progress of novel pharmaceutical development, especially in improving metabolic stability.

Strategies for Herbal Knowledge Inheritance Through Non-Formal Education in Traditional Villages

In the current context of globalization, the process of passing on traditional knowledge, particularly in relation to medicinal plant applications, faces significant hurdles. Kampung Adat Dangiang, facing this challenge, has initiated the establishment of Sekolah Adat as a non-formal education initiative aimed at the conservation and transmission of cultural and traditional knowledge to the next generation. This research investigates Sekolah Adat in Kampung Dangiang as an institution that plays an important role in knowledge preservation, where traditional healing principles and ritualistic practices are passed on across generations. Qualitative methodology, specifically case studies, was adopted in this research, providing a more narrative and exploratory approach to data collection. Through direct interaction, observation of daily rituals, and literature review, the research gathered information enriched by snowball sampling techniques from informants. The results reveal Sekolah Adat as an entity steeped in traditional values, functioning not only as an educational institution but as a living repository of medicinal plant knowledge and ritual practices. The Sekolah Adat introduces a unique pedagogical approach, combining lectures, demonstrations and practical applications, which overall enriches the spiritual existence of learners. The program creates a synergy between traditional herbal wisdom, modern chemical principles, and deep inner healing techniques. Although this integration of tradition and modernity poses challenges, especially in the aspect of scientific validation of ancestral practices, a strong commitment to the efficacy of traditional medicine, supported by generations of knowledge and anecdotes, continues to overcome such obstacles. In conclusion, Sekolah Adat Dangiang stands as a testament to the resilience of traditions that are able to adapt elegantly amidst the changing modern world. It signifies the importance of local wisdom in keeping cultural heritage alive and relevant amidst fast-changing global dynamics.

Development of Web-Based Modules to Improve Digital Literacy and Learning Outcomes in Science Learning

This study aims to produce e-modules for science lessons that are valid, practical, and effective to improve junior high school students' digital literacy and learning outcomes. This study used research and development methods with the ADDIE model. The data collection techniques were observation, interviews, validation sheets, student activity sheets using e-modules, learning outcomes tests, digital literacy assessment rubrics, student response questionnaires, and documentation. The data analysis techniques used in this study were validity test techniques, practicality tests and effectiveness tests. The results of the validation data analysis obtained a validation value of 91% with a very valid category, including aspects of content and construct validation. The practicality analysis results obtained a value of 91.20% with an efficient category. The results of the effectiveness analysis were based on the increase in learning outcomes, which resulted in an n-gain of 0.61 with a moderate category. Meanwhile, the results of the effectiveness analysis based on the ability of digital literacy indicators got an n-gain of 0.71 with a high category. The results of the effectiveness analysis were seen from student questionnaires, which scored 83.23% in the excellent category. Thus, the e-module product that has been developed is said to be feasible to be implemented in junior high school science learning to improve digital literacy and learning outcomes of junior high school students.

AERODROME MAPPING DATA DESIGN DEVELOPMENT APPROACH HIGHLIGHTS

In accordance with the trend in further intellectualization of mapping data design systems, this article deals with the problem of development methods for obtaining aerodrome mapping data more efficient than the existing methods that use manual vectorization on a raster base. Data usage areas were listed, including automated control systems, flight deck automation, simulators and simulation systems. Much attention was given to main aerodrome mapping data design approaches analysis, which shows that existing aerodrome cartographic data obtaining methods lack functionality. A description and basic requirements for an aerodrome mapping data design system, as well as requirements for the data itself, are presented. Additionally, data validation aspects are noted, including those of a taxi route network. Results of the research suggest that computer-aided design methods make it possible to significantly reduce labor intensity and time required to obtain mapping data. A new approach, which consists in using computer-aided design methods for such data, is proposed. Areas in which this approach can provide a significant effect were identified. Methods, algorithms and programs that implement the approach are being developed in context of the new data design system. It will provide a wide range of functions for aerodrome mapping design. General scheme of the system describing its main components was given. An example of aircraft parking elements design as a part of routing network design is provided.

An appraisal of statistical and probabilistic models in highway pavements

Accurate performance prediction is crucial for safe and efficient travel on highway pavements. Within pavement engineering, statistical models play a pivotal role in understanding pavement behavior and durability. This comprehensive study critically evaluates a spectrum of statistical models utilized in pavement engineering, encompassing mechanistic-empirical, Weibull distribution, Markov chain, regression, Bayesian networks, Monte Carlo simulation, artificial neural networks, support vector machines, random forest, decision tree, fuzzy logic, time series analysis, stochastic differential equations, copula, hidden semi-Markov, generalized linear, survival analysis, response surface methodology and extreme value theory models. The assessment meticulously examines equations, parameters, data prerequisites, advantages, limitations, and applicability of each model. Detailed discussions delve into the significance of equations and parameters, evaluating model performance in predicting pavement distress, performance assessment, design optimization, and life-cycle cost analysis. Key findings emphasize the critical aspects of accurate input parameters, calibration, validation, data availability, and model complexity. Strengths, limitations, and applicability across various pavement types, materials, and climate conditions are meticulously highlighted for each model. Recommendations are outlined to enhance the effectiveness of statistical models in pavement engineering. These suggestions encompass further research and development, standardized data collection, calibration and validation protocols, model integration, decision-making frameworks, collaborative efforts, and ongoing model evaluation. Implementing these recommendations is anticipated to enhance prediction accuracy and enable informed decision-making throughout highway pavement design, construction, maintenance, and management. This study is anticipated to serve as a valuable resource, providing guidance and insights for researchers, practitioners, and stakeholders engaged in asphalt engineering, facilitating the effective utilization of statistical models in real-world pavement projects.

Analytical Method Development and Validation Of Stability Indicating RP-HPLC Method For Assay and Related Substances of Paracetamol and Caffeine Effervescent Tablets: Review

he ongoing, interdependent tasks related to the departments of research and development, quality control, and quality assurance are the creation and validation of analytical methods. Analytical methods are essential for risk management and equivalency assessments. It aids in the development of acceptability standards unique to a product and the consistency of outcomes. Validations establish whether the analytical process is appropriate for the goal for which it was designed. A review of the literature indicates that paracetamol and caffeine can be determined individually or in combination with other medications using analytical techniques based on UV spectroscopy, RP-HPLC, and HPTLC. The parameters were checked for correctness, precision, robustness, and other aspects of analytical validation in accordance with ICH guidelines. The discovered techniques can be applied to the bulk and tablet dosage form analysis of paracetamol and caffeine in effervescent form since they are straight forward, sensitive, and repeatable. The review also outlines the applicability and constraints of numerous published analytical techniques for paracetamol and caffeine analysis. Stability studies have to be conducted on time and in compliance with the standards issued by the World Health Organization, International Conference of Harmonization, and other bodies. The capacity of a pharmaceutical product to meet the physical, chemical, microbiological, toxicological, protective, and informational requirements of a specific formulation in a particular container-closure system is known as its stability. It also ensures that a pharmaceutical product's effectiveness, safety, and performance will be maintained for the duration of its shelf life, which is seen as a need for approval and acceptability. The requirement for ongoing quality and purity monitoring of medications and products gave rise to various stability test techniques. This review covers the various drug substance stability categories as well as the applicability of various techniques for drug substances that are stable, the applicability of various methods used to test the pharmaceutical product's stability, guidelines released to test the pharmaceutical product's stability, protocols for stability testing that outline the essential elements of a well-managed and regulated stability test, and other aspects of stability are all covered in this review. The researcher working on paracetamol and caffeine in effervescent form will greatly benefit from this thorough review study.

Development of Web-Based Learning Media for Junior High School Level Physics Olympiad Material With Islamic Integration

The Development of Islamic Integrated Learning Website-Based Media for Junior High School Physics Olympiad Material aims to determine the feasibility of the website-based learning media for junior high school physics Olympiad material integrated with Islam. The learning media is developed based on the stages in this research, adopting modifications from Borg & Gall. The data collection instrument used in this research and development is a questionnaire. The results of the development of the junior high school physics Olympiad material website integrated with Islam meet the validity criteria. The average total score of the website media expert is 89.2, the material expert's website validation is 86.15, and the integration of Islamic website validation is 81.82. Considering the overall aspects of validation and meeting the feasibility criteria, it is declared in the "valid/appropriate" category.

PHYSICOCHEMICAL ANALYSIS OF SIDDHA POLY-HERBAL FORMULATION NELLIMULLI ILAGAM

Introduction: The Siddha system is an ancient, holistic system. The medicine in this system is prepared from raw materials of herbs, metals, minerals and animal products. In recent years, considerable research has focused on validation and standardisation aspects. Nellimulli ilagam is a polyherbal Siddha formulation used to manage Veluppu noi. Aim: To study the physicochemical analysis of Nellimulli ilagam. Methods: Standardization parameters such as organoleptic characteristics, physicochemical analysis, test for aflatoxins, pesticide residues, specific pathogens, and heavy metal analysis were carried out as per PLIM guidelines. Results: The results obtained from the trial drug Nellimulli ilagam study show that it has a dark, brownish-coloured semi-solid texture with a strong characteristic odour and is non-free-flowing. Physicochemical analysis reveals that pH was 7.2, total ash value was 10±0.4 and acid insoluble ash value was 0.02±0.004. Loss on drying at 105 0C is 8.4±0.9. The test for aflatoxins and pesticide residues showed negative results. Test for microbial contamination and specific pathogen shows absent. Test for heavy metals shows below the limit of quantification (BLQ).

Problem-Based Learning (PBL) Physics Teaching Books Newton’s Gravity Force

The purpose of this research is to test the validity and feasibility of physics textbooks that have been developed based on Problem Based Learning (PBL) on Newton's gravitational force material. This research uses development research methods. The validation sheet is used as a research instrument. The validation sheet was validated by two experts and declared valid according to predetermined criteria. Textbook validation data was collected from two experts, one textbook media expert and one physics material expert. There are two aspect criteria that are tested for validity, the form of dialogical and interactive presentation of language and the contextual nature of textbooks. The purpose of this research approach is to describe the effectiveness, validity and feasibility of using physics textbooks. The research results obtained are the percentage of aspects of dialogic and interactive language validation as well as aspects of contextual nature that have been tested by material experts obtained an average percentage of 87.5%, which means that the physics textbooks that have been developed are included in the feasible criteria. The results of the research tested by media experts on aspects of dialogic and interactive language as well as on aspects of contextual nature both obtained an average percentage of 100%. This means that a physics textbook based on Problem Based Learning (PBL) on Newton's gravitational force is very feasible to be tested based on validity testing by one material expert and one media expert.

Annual Daily Irradiance Analysis of Clusters in Mexico by Machine Learning Algorithms

The assessment of solar resources involves the utilization of physical or satellite models for the determination of solar radiation on the Earth’s surface. However, a critical aspect of model validation necessitates comparisons against ground-truth measurements obtained from surface radiometers. Given the inherent challenges associated with establishing and maintaining solar radiation measurement networks—characterized by their expense, logistical complexities, limited station availability and the imperative consideration of climatic criteria for siting—countries endowed with substantial climatic diversity face difficulties in station placement. In this investigation, the measurements of annual solar irradiation, from meteorological stations of the National Weather Service in Mexico, were compared in different regions clustered by similarities in altitude, TL Linke, albedo and cloudiness index derived from satellite images; the main objective is to find the best ratio of annual solar irradiation in a set of clusters. Employing machine learning algorithms, this research endeavors to identify the most suitable model for predicting the ratio of annual solar irradiation and to determine the optimal number of clusters. The findings underscore the efficacy of the L-method as a robust technique for regionalization. Notably, the cloudiness index emerges as a pivotal feature, with the Random Forest algorithm yielding superior performance with a R2 score of 0.94, clustering Mexico into 17 regions.

AI for Detection of Tuberculosis: Implications for Global Health.

Tuberculosis, which primarily affects developing countries, remains a significant global health concern. Since the 2010s, the role of chest radiography has expanded in tuberculosis triage and screening beyond its traditional complementary role in the diagnosis of tuberculosis. Computer-aided diagnosis (CAD) systems for tuberculosis detection on chest radiographs have recently made substantial progress in diagnostic performance, thanks to deep learning technologies. The current performance of CAD systems for tuberculosis has approximated that of human experts, presenting a potential solution to the shortage of human readers to interpret chest radiographs in low- or middle-income, high-tuberculosis-burden countries. This article provides a critical appraisal of developmental process reporting in extant CAD software for tuberculosis, based on the Checklist for Artificial Intelligence in Medical Imaging. It also explores several considerations to scale up CAD solutions, encompassing manufacturer-independent CAD validation, economic and political aspects, and ethical concerns, as well as the potential for broadening radiography-based diagnosis to other nontuberculosis diseases. Collectively, CAD for tuberculosis will emerge as a representative deep learning application, catalyzing advances in global health and health equity. Keywords: Computer-aided Diagnosis (CAD), Conventional Radiography, Thorax, Lung, Machine Learning Supplemental material is available for this article. © RSNA, 2024.

Incorporating uncertainty into the validation of automotive crash simulation models for component analysis

The design and development of crashworthy vehicles depend increasingly on credible crash simulation results. This credibility requires a careful process of verification and validation (V&V). The former relates to assessing the correctness of the calculation while the latter relates to the appropriateness of the physical and numerical test results. In this context, various sources of uncertainty exist in crash tests as well as in simulation models, which can influence the validation outcomes. Hence, it is essential to study statistical validation approaches for crash applications. In this paper, we elaborate on two important aspects of validation for crash simulation models: quantification of the credibility of simulation models, and consideration of uncertainties in the validation. Limited and noisy experimental data, typical in crash applications, impose a challenge on the investigation of validation approaches. To address these challenges, we use synthetic experimental results in our study. A crash-box model is validated using the V&V20-2009 validation standard. Two case studies are considered. The first case study aims to show the application of the V&V20 approach to a crash problem. The second case is a more complex scenario and aims to explore the impact of different experimental factors, such as experimental noise, hidden uncertainties, and the number of experiments on the validation results. In the end, we examine how underlying assumptions in the validation approach affect the conservativity of the validation results.

Pengembangan Media Pembelajaran Sejarah Indonesia Berbasis Infografis Materi Kekuasaan Kongsi Dagang VOC di SMA Negeri 10 Medan

The use of learning media is increasingly being used day by day. History is one example of a subject that feels quite high benefits from the use of learning media. This research aims to develop infographic media in history learning at the high school level. To determine the quality of infographic media as a learning medium in terms of feasibility validation aspects, and to determine the effectiveness of infographic media in learning based on student learning outcomes. This research was carried out at SMA Negeri 10 Medan, with the research sample being class X IPS 1. This research used the R&D method. The data collection technique is in the form of a questionnaire or questionnaire, while the data analysis technique uses percentage calculations. The results of this research indicate that the media developed meets the requirements and is suitable for use as learning media. The validation results of material experts and media experts respectively obtained a score percentage of 98% and 96%. Meanwhile, the results of small group trials showed a score percentage of 84%. Then, the results of large group use trials and effectiveness tests respectively showed a score percentage of 84% and 93%. With these results, it can be concluded that this infographic media is very valid and therefore suitable and effective for use in learning.

Improved Path Testing Using Multi-Verse Optimization Algorithm and the Integration of Test Path Distance

Emerging technologies in artificial intelligence (AI) and advanced optimization methodologies have opened up a new frontier in the field of software engineering. Among these methodologies, optimization algorithms such as the multi-verse optimizer (MVO) provide a compelling and structured technique for identifying software vulnerabilities, thereby enhancing software robustness and reliability. This research investigates the feasibility and efficacy of applying an augmented version of this technique, known as the test path distance multiverse optimization (TPDMVO) algorithm, for comprehensive path coverage testing, which is an indispensable aspect of software validation. The algorithm’s versatility and robustness are examined through its application to a wide range of case studies with varying degrees of complexity. These case studies include rudimentary functions like maximum and middle value extraction, as well as more sophisticated data structures such as binary search trees and AVL trees. A notable innovation in this research is the introduction of a customized fitness function, carefully designed to guide TPDMVO towards traversing all possible execution paths in a program, thereby ensuring comprehensive coverage. To further enhance the comprehensiveness of the test, a metric called ‘test path distance’ (TPD) is utilized. This metric is designed to guide TPDMVO towards paths that have not been explored before. The findings confirm the superior performance of the TPDMVO algorithm, which achieves complete path coverage in all test scenarios. This demonstrates its robustness and adaptability in handling different program complexities.

Validation Aspects for Grid-Forming Converters Based on System Characteristics and Inertia Impact

Grid-forming converters are considered a key technology for electrical grids with a high share of renewable energy. However, there is a lack of a general, robust and verifiable definition of what constitutes this behaviour. Therefore, this paper presents three simple scenarios that enable such a definition. They are based on simple black-box simulations that allow manufacturers to protect their development work. It can be shown that grid forming can be clearly distinguished from grid-following controls by their grid behaviour in the proposed scenarios. Extensive results illustrate this and also provide suggestions to deepen the understanding of grid-forming grid behaviour and its impact on system inertia. These findings should inspire the development of a clear definition and ultimately new requirements for converter systems.