System Level Research Articles

UnifiedGreatMod: A New Holistic Modelling Paradigm for Studying Biological Systems on a Complete and Harmonious Scale.

Computational models are crucial for addressing critical questions about systems evolution and deciphering system connections. The pivotal feature of making this concept recognisable from the biological and clinical community is the possibility of quickly inspecting the whole system, bearing in mind the different granularity levels of its components. This holistic view of system behaviour expands the evolution study by identifying the heterogeneous behaviours applicable, for example, to the cancer evolution study. To address this aspect, we propose a new modelling paradigm, UnifiedGreatMod, which allows modellers to integrate fine-grained and coarse-grained biological information into a unique model. It enables functional studies by combining the analysis of the system's multi-level stable states with its fluctuating conditions. This approach helps to investigate the functional relationships and dependencies among biological entities. This is achieved thanks to the hybridisation of two analysis approaches that capture a system's different granularity levels. The proposed paradigm was then implemented into the open-source, general modelling framework GreatMod, in which a graphical meta-formalism is exploited to simplify the model creation phase and R languages to define user-defined analysis workflows. The proposal's effectiveness was demonstrated by mechanistically simulating the metabolic output of Echerichia coli under environmental nutrient perturbations and integrating a gene expression dataset. Additionally, the UnifiedGreatMod was used to examine the responses of luminal epithelial cells to Clostridium difficile infection. GreatMod https://qbioturin.github.io/epimod/, epimod_FBAfunctions https://github.com/qBioTurin/epimod_FBAfunctions, first case study E.coli https://github.com/qBioTurin/Ec_coli_modelling, second case study C. difficile https://github.com/qBioTurin/EpiCell_CDifficile. Supplementary data are available at Bioinformatics online.

Formation of sets of septenary sequences with low cross-correlation level for digital information transmission systems

Formation of sets of septenary sequences with low cross-correlation level for digital information transmission systems

VanGO: Alaminos to Dagupan Van Scheduling, Queuing, and Booking System for the Convenience of Commuters

Abstract: The VanGO Alaminos to Dagupan Van scheduling, queuing, and booking system for convenience commuters addresses the challenges faced by van drivers, dispatchers, and commuters along the route, focusing on enhancing transportation efficiency and improving the overall travel experience. Using the Rapid Application Development (RAD) methodology, this study aims to design and develop a strong system that integrates key features such as real-time updates on van locations, efficient route optimization, and reliable scheduling algorithms. Through interviews, observations, and literature review, insights were gathered into the commuting experience and operational challenges along the specified route. A purposive sampling method was employed to select respondents, resulting in a total of 50 participants including commuters and van drivers/dispatchers. The system's acceptance level will be evaluated using a Likert Scale survey questionnaire, and statistical analysis will be conducted to validate usability and performance. By addressing the inefficiencies in van scheduling, queuing, and booking processes, this study contributes to the improvement of transportation systems and enhances commuter satisfaction along the Alaminos to Dagupan route.

The Role of CRISPR-Cas9 in Gene Editing

The CRISPR-Cas9 technique is a contemporary technology that has transformed the process of genetic modification, allowing scientists to target genomes in living organisms with precision and simplicity. Numerous practical applications of significant importance, including the introduction of new genes into living cells, are facilitated by the CRISPR-Cas9 system's advanced level of gene targeting, precision, and simplicity of use. An enigmatic process involving repeated DNA sequences in E. coli initiated the emergence of this CRISPR-Cas9 mechanism. After observing this phenomenon in bacteria, scientists initiated an investigation into its function. It was noted that E. coli employs it as a self-defence mechanism against bacteriophage attacks and plasmids. CRISPR-Cas9, a novel method for genetic modification, was created as a result of this investigation. This system has been re-engineered by scientists to be more broadly applicable, allowing for the modification of the genetic code of virtually any organism, surpassing the scope of self-defence. The CRISPR-Cas9 system-based gene editing mechanisms have the potential to produce substantial results that were previously difficult to achieve. Nevertheless, the question of genetic modification through the application of this technology prompts debates and demands for the resolution of the ethical, social, and legal issues that are associated with its application. The potential applications of the CRISPR-Cas9 system are seemingly boundless.

Determination of Zea Mays Plant Fertility Level in Automatic Fodder Systems using Supervised Learning based on GLCM and Physical Feature

The problem during the dry season is the availability of animal feed, especially for cattle. One of the efforts made is to use fermented feed and corn fodder. Automated feedstock monitoring and control is one of the technologies that has been developed. This study proposes a method to determine the fertility of Zea May sp plants in automatic fodder using supervised learning based on Self-Organizing Map (SOM), Gray Level Co-occurrence Matrix (GLCM), and physical features. The results showed that the system worked satisfactorily, where both methods achieved an accuracy of 93.5% on 3-day Zea Mays fodder using SOM and the highest on 12-day Zea Mays fodder using both methods with an accuracy of 96%. Although this system has shown good performance using both SOM and K-means, in some conditions, K-means achieved higher performance. These contributions are expected to help farmers provide animal feed.

The Evaluation of a New ELISA-Based Kit for Total Microcystins as an Early Detection Tool for Microcystin Blooms in Source Waters and Its Application State-Wide to Oregon Source and Finished Drinking Waters.

Due to cyanobacterial toxin (cyanotoxin) contamination issues in 2018, the city of Salem, Oregon, issued a 33-day do-not-drink advisory for vulnerable people among the 200,000 residents. After the incident, the state of Oregon put in place drinking water rules to require the routine testing of raw water, as well as finished water, in cases where the raw water cyanotoxin concentrations exceeded trigger values. The United States Environmental Protection Agency (EPA) total microcystins drinking water health advisory level (HAL) for small children is 0.3 µg/L. This is equivalent to the minimum reporting level (MRL) for EPA Method 546. Consequently, there was no ability to provide early warnings via toxin testing for total microcystins using the EPA method. In this study, we performed a comparison of the precision and accuracy of the enzyme-linked immunosorbent assay (ELISA) described in the EPA method to a more sensitive assay, the Streptavidin-enhanced Sensitivity (SAES) assay. Based on these precision and accuracy studies and quantitation limit determinations and confirmations, the EPA Office of Ground Water and Drinking Water (OGWDW) has concluded the SAES kit meets the requirements of EPA Method 546. With an MRL that is one-third of the original concentration, the new kit provides a small but critical window for identifying early warnings. Challenges remain with providing early warnings due to the variability in bloom dynamics; however, the new MRL allowed Oregon to lower the trigger level for susceptible systems, thereby providing an additional early warning.

Nonbonded Molecular Interaction Controls Aggregation Kinetics of Hydrophobic Molecules in Water.

Molecular aggregation frequently occurs during material synthesis, cellular processes, and drug delivery systems, often resulting in decreased performance and efficiency. One major reason for such aggregation in an aqueous solution is hydrophobicity. While the basic understanding of the aggregation process of hydrophobic molecules from a thermodynamic standpoint is known, the present literature lacks a connection between the aggregation kinetics and the molecular basis of hydrophobicity. This study explores how various fluorescent probes (rhodamine dyes) aggregate in an aqueous solution due to their hydrophobicity. The method employs a combination of modeling and characterization to comprehend the aggregation process by examining the nonbonded intermolecular interactions. The aggregation kinetics was analyzed by measuring the average diffusivity of the molecules using fluorescent correlation spectroscopy and NMR diffusion measurements. Through all-atom molecular dynamics (MD) simulations, it has been observed that the level of hydrophobicity is strongly correlated to the total number of hydrogen bonds between water molecules and dyes. In addition, the aggregation frequency of colliding species, which depends on the concentration, is inversely related to hydrogen bonding and the diffusivity of the molecules. This study of small molecules was applied to predict protein aggregation rates, demonstrating strong alignment with the existing literature. The study has also helped to identify and understand the concentration at which a hydrophobic molecule does not aggregate in an aqueous solution. The method developed here could help investigate the aggregation process and its root causes at the molecular level in aqueous systems to develop strategies to control it.

Advancing haptic realism: modelling grasp contact vibrations for enhanced virtual environment interaction

Abstract In haptic technology, achieving realistic tactile feedback is crucial for enhancing the user experience in virtual environments. Previous studies lack effective methods for transmitting high-frequency vibrations crucial for realistic tactile feedback in haptic interfaces, highlighting the need for our research to address this gap. This paper explores the application of a tactile gripping interface to transmit the high-frequency vibrations produced when contacting a hard object's surface. These short vibrations improve the tactile sensation of hard virtual surfaces when overlaid on traditional position-based force feedback within a haptic environment. The enhanced realism of virtual objects is achieved by effectively estimating the vibration composition from user-induced parameters. This work presents a prototype grasping interface and empirically demonstrates this device's utility. We examine empirical grasp contact data, recorded and interpreted, to recognise the relationship between dynamic user-controlled parameters and the resulting vibration transients. This relationship effectively incorporates these changing dynamics to model the grasp impact and estimate the essential system parameters to understand the influence of the user's grasp force. Through our multi-point grasping interface design, this work demonstrates a mathematical relationship between the user's grasp force and the high-frequency vibrations from contact with hard surfaces. The study found that the proposed haptic interface had an RMSE of 0.05, demonstrating the system's high level of accuracy. This low RMSE value indicates that the predicted vibrations closely matched the actual measured vibrations, proving the effectiveness of our methods through objective validation.

A Comprehensive Survey on the Integrity of Localization Systems.

This survey extends and refines the existing definitions of integrity and protection level in localization systems (localization as a broad term, i.e., not limited to GNSS-based localization). In our definition, we study integrity from two aspects: quality and quantity. Unlike existing reviews, this survey examines integrity methods covering various localization techniques and sensors. We classify localization techniques as optimization-based, fusion-based, and SLAM-based. A new classification of integrity methods is introduced, evaluating their applications, effectiveness, and limitations. Comparative tables summarize strengths and gaps across key criteria, such as algorithms, evaluation methods, sensor data, and more. The survey presents a general probabilistic model addressing diverse error types in localization systems. Findings reveal a significant research imbalance: 73.3% of surveyed papers focus on GNSS-based methods, while only 26.7% explore non-GNSS approaches like fusion, optimization, or SLAM, with few addressing protection level calculations. Robust modeling is highlighted as a promising integrity method, combining quantification and qualification to address critical gaps. This approach offers a unified framework for improving localization system reliability and safety. This survey provides key insights for developing more robust localization systems, contributing to safer and more efficient autonomous operations.

INTERNATIONAL AND NATIONAL LEGAL MECHANISMS OF JUDICIAL LIABILITY IN THE CONDITIONS OF ECONOMIC GLOBALISATION OF MODERN SOCIETY

The subject matter of the study is the conceptual, theoretical, empirical, methodological and applied foundations of international and national legal mechanisms of judicial liability in the context of economic globalisation of modern society. Methodology. The present study employed a combination of general scientific and special legal methodologies. Through meticulous analysis, the quantitative and qualitative characteristics of the economic and legal essence of an independent and impartial judiciary as the nation's sole arbiter of justice were systematically delineated. The synthesis yielded a comprehensive overview of the legal framework governing the judicial accountability of judges across diverse legal systems, with particular consideration for each system's economic level of development. The employment of a comparative legal methodology has facilitated the identification of both common and distinctive characteristics in both international and national legislation. This is a scientific development that is indicative of the legal mechanism for holding judges to disciplinary liability. The formal-legal method established the foundations for formulating conclusions regarding the effectiveness of existing national legal regimes for holding judges accountable. The purpose of the present article is to determine the specific features of international and national legal mechanisms of judicial liability in the context of economic globalisation in modern societies. The results of the study show that the existing international legal mechanism of judicial liability developed by international institutions is quite effective and promising for implementation within the framework of national legal regimes, and the national mechanism of judicial liability needs to be improved both in terms of procedure and means of its implementation in connection with the economic development of society. Conclusion. The establishment of functional indicators of the judiciary has been undertaken, which are convergent in combination with economic indicators of the population's well-being, conditions for opening one's own business, ensuring financial and banking stability, GDP growth, the level of development of relevant sectors of industry and the economic sphere as a whole, etc. Among the indicators that reproduce the productivity of all three branches of government, the following are highlighted: the government efficiency index - the executive branch, the legislation quality index - the legislative branch, the rule of law index - the judiciary. A direct dependence of the economic development and rule of law indices has been revealed, since under the condition of ensuring the latter, there is a guarantee of the harmonious existence of all sectors of society, and conditions are created to prevent the emergence of existential threats to the national interests of the state, including the provision of human rights and freedoms. The mechanism for bringing judges to disciplinary responsibility has been established in accordance with international standards, including 1) a special procedure for bringing judges to disciplinary responsibility, which is defined by law; 2) the formation of an independent body that should consider such cases; 3) ensuring the right of a judge to participate in such procedure directly or through a representative, to exercise his right of defence and to express his opinion; 4) the right to appeal against the decision taken on the basis of the results of this procedure; 5) the exhaustiveness of the sanctions that can be applied and their proportionality. Within the framework of the national legal systems of the countries under consideration, the features of holding judges accountable in relation to their professional activities and for offences committed outside them are determined, which mediate the implementation of the content of the immunity and immunity of such officials. The procedure for holding judges criminally and disciplinarily liable is highlighted separately, and the reasons, grounds, procedure and subjects of the above-mentioned proceedings are determined, which indicates the special status of bodies that ensure the achievement of a social compromise in the influence of society on the judiciary, in combination with the construction of ensuring the immunity of judges.

Investigation of the Potential Mechanism of Compound Dragon's Blood Capsule against Myocardial Ischemia Based on Network Pharmacology.

Dragon's blood is widely consumed in China, Vietnam and Laos to promote blood circulation. A Compound Dragon's blood capsule (CDC) is a patented medicine composed of dragon's blood, notoginseng, and borneol. This combination is purported to stabilize coronary heart disease and myocardial ischemia. However, the possible mechanisms and the characterization of its drug targets' relevance at the systemic level remain unclear. The present study aims to reveal the potential mechanisms of CDC's anti-myocardial ischemia effect. The potential mechanisms were investigated by network pharmacology and qRT-PCR was used to verify the expression levels of key genes of PI3k-Akt pathway. S1PR2 and AGTR1 were the common targets, which involved 6 biological processes annotated by KEGG and GO analysis. The qRT-PCR results showed a remarkable increase in the expression of Pi3k, Pdk1, Akt, Mdm2, Bcl2, and mTOR. Results also showed a decline in the expression of P53 and Casp3 after CDC intervention. CDC has a significant anti-myocardial ischemia effect through the PI3k/Akt pathway, which demonstrates that CDC is a suitable adjuvant to treat CHD and provides a theoretical basis for its further clinical application.

Unraveling the spatial heterogeneity of dissolved organic matter characteristics from the optical level in slope-gully systems

Unraveling the spatial heterogeneity of dissolved organic matter characteristics from the optical level in slope-gully systems

Limestone reaction in sandy soil: Rate effects, limestone type, moisture regime, and time

AbstractAn experiment was conducted in the greenhouse facilities of Embrapa Maize and Sorghum to evaluate the limestone reaction in sandy soil based on rates, limestone type, effective calcium carbonate equivalent (ECCE), and moisture regime over time. A factorial design of 4 × 2 + 3 was adopted, consisting of four limestone rates with 76% ECCE (0, 1, 2, and 4 Mg ha−1), two irrigation types (daily and monthly, simulating constant and intermittent moisture regime), and three additional treatments (three rates of “filler” limestone—99% ECCE—under monthly irrigation). Soil chemical characteristics were analyzed at 1, 2, 3, 6, and 12 months after treatment application. Soil fertility improved at the first month after treatment application, with emphasis on higher limestone rates, monthly moisture regime, and filler lime stone. The highest limestone rate did not increase the pH above 7.0. The recommended limestone rate was insufficient to elevate Ca + Mg levels to the adequate level for current production genotypes and systems, which demand higher standards. These outcomes reinforce the need for carrying out further studies and potential revision in liming recommendations for sandy soils.

Stochastic optimal harmonic suppression with permissible photovoltaic penetration level for grid-linked systems using Monte Carlo-based hybrid NSGA2-MOPSO

Stochastic optimal harmonic suppression with permissible photovoltaic penetration level for grid-linked systems using Monte Carlo-based hybrid NSGA2-MOPSO

Image charge effects under metal and dielectric boundary conditions.

Theimage charge(IC)effect is a fundamental problem in electrostatics. However, proper treatment at the continuum level for many-ion systems, such as electrolyte solutions or ionic liquids, remains an open theoretical question. Here, we demonstrate and systematically compare the IC effects under metal and dielectric boundary conditions (BCs), based on a renormalized Gaussian-fluctuation theory. Our calculations for a simple 1:1 symmetric electrolyte in the point-charge approximation show that the double-layer structure, capacitance, and interaction forces between like-charged plates depend strongly on the types of boundaries, even in the weak-coupling regime. Like-charge attraction is predicted for both metal and dielectric BCs. Finally, we comment on the effects of a dielectricallysaturated solvent layer on the metal surface. We provide these results to serve as a baseline for comparison with more realistic molecular dynamics simulations and experiments.

Ecotoxicological and metabolomic investigation of chronic exposure of Daphnia magna (Straus, 1820) to yttrium environmental concentrations

Ecotoxicological and metabolomic investigation of chronic exposure of Daphnia magna (Straus, 1820) to yttrium environmental concentrations

Differences in Symptom Burden in Primary Brain Tumor Patients Based on Sex, Race, and Ethnicity: a Single-Center Retrospective Study.

Symptom burden affects quality of life and prognosis in primary brain tumor (PBT) patients. Knowing whether symptom burden varies based on sex, race, or ethnicity may affect the interpretation of the relationship between symptoms and survival may reveal issues with applying the tools to measure symptom burden to different groups and may identify inequities in symptom management that need to be addressed at a system level. To determine whether symptoms in PBT patients vary across demographic groups, we conducted a retrospective chart review of symptom burden collected as part of routine care in a diverse population. Patient demographics and scores on the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) module were extracted from the electronic medical record for patients seen in the Inova Neuro-oncology Clinic between March 2021 and June 2022. MDASI-BT scores were compared based on side of tumor, sex, race, and ethnicity for the entire population and for the subset with gliomas. We included 125 people, of whom 85 had gliomas. For both the entire group and the subgroup with gliomas, about 40% were female and about 40% were non-White race. No differences in symptom burden were seen between males and females. Pain and numbness/tingling symptom burden were higher in both the entire population and the glioma subgroup for people of Hispanic/Latino/Spanish ethnicity and for people of races other than White or Middle Eastern self-identification. Pain, weakness, and numbness/tingling varied significantly across racial and ethnic groups. Further research is needed to validate this finding in other populations and determine its cause.

Joint Optimization of Mode Switching, Loading Level, and Maintenance for Production Systems With Dynamic Tasks

Joint Optimization of Mode Switching, Loading Level, and Maintenance for Production Systems With Dynamic Tasks

The Evolution of the Acylation Mechanism in β-Lactamase and Rapid Protein Dynamics.

β-Lactamases are a class of well-studied enzymes that are known to have existed since billions of years ago, starting as a defense mechanism to stave off competitors and are now enzymes responsible for antibiotic resistance. Using ancestral sequence reconstruction, it is possible to study the crystal structure of a laboratory resurrected 2-3 billion year-old β-lactamase. Comparing the ancestral enzyme to its modern counterpart, a TEM-1 β-lactamase, the structural changes are minor, and it is probable that dynamic effects play an important role in the evolution of function. We used molecular dynamics simulations and employed transition path sampling methods to identify the presence of rate-enhancing dynamics at the femtosecond level in both systems, found that these fast motions are more efficiently coordinated in the modern enzyme, and examined how specific dynamics can pinpoint evolutionary effects that are essential for improving enzymatic catalysis.

Methodological framework for impact evaluation of Building‐Integrated Greenery (BIG‐impact)

Methodological framework for impact evaluation of Building‐Integrated Greenery (BIG‐impact)