Regulatory Systems Research Articles

Microbial Primer: Phase variation - survival and adaptability by generation of a diverse population.

Phase variation is defined as the rapid and reversible switching of gene expression, and typically occurs in genes encoding surface features in small genome bacterial pathogens. Phase variation has evolved to provide an extra survival mechanism in bacteria that lack multiple 'sense-and-respond' gene regulation systems. Many bacterial pathogens also encode DNA methyltransferases that are phase-variable, controlling systems called 'phasevarions' (phase-variable regulons). This primer will summarize the current understanding of phase variation, describing the role of major phase-variable factors, and phasevarions, in bacterial pathobiology.

A holistic approach to different regulations for acoustic improvements in industrial facilities

With the developing technology and mechanization, the number of industrial facilities has increased. It is important for the worker’s physical and mental health to be in suitable working conditions. This paper analyses the regulations applied in the examination and evaluation of the acoustic environment in industrial facilities. The European Parliament and Council Directive, the United States, Singapore, Canada, Australia, Mexico, Japan, and WHO principles were analysed in detail. Simultaneously, analyses were conducted on the auditory perception of the workers in industrial facilities. As a result of the study, 85, 87, and 90 dBA noise exposure levels were determined for 8 h in different regulations examined. It has been determined that the regulative systems for the auditory perception of the workers in industrial facilities are insufficient. It was found necessary to develop regulation systems for evaluating noise exposure levels and the auditory perception of the workers together. It is important for the occupational health and safety of workers to develop a holistic approach in the update and revision of international regulation and to evaluate the control mechanisms within this scope. The protection of mental and physical health of the workers is presented as the most fundamental requirement. Moreover, it should be ensured that the noise control measures that can be taken (at the source, at the transmission path, and at the receiver) are formed by reducing the noise exposure and increasing the auditory perception of the workers in a positive view.

Distributed control of virtual energy storage systems for voltage regulation in low voltage distribution networks subjects to varying time delays

Distributed communication-based strategies are popular for regulating nodal voltages in distribution networks with high penetration of Photovoltaic (PV) sources. Time delays inevitably pose challenges to efficient voltage regulation and power sharing. In response, this paper presents a distributed, event-triggered voltage regulation approach that enables power sharing across virtual energy storage systems (VESS) with different parameters while accommodating diverse time delays. The process begins by determining the delay margin for the primary Volt/Watt controller in a low-voltage distribution network (LVDN), laying the foundation for stable feedback control gain design. To accommodate any arbitrary large and time-varying delays, a distributed resilient event-triggered secondary controller for VESS is designed to share voltage regulation tasks according to their capacities and state of energy (SoE) values. A mathematical analysis, grounded in the Lyapunov–Krasovskii approach, evaluates the stability and convergence of the proposed controller amidst time delays thoroughly. To validate the proposed method, simulation studies are conducted, which demonstrate the effectiveness in mitigating voltage limit violations, even with variable communication delays, and highlight balanced power sharing and SoE among VESS.

Cellular Stress in Dry Eye Disease-Key Hub of the Vicious Circle.

Disturbance or insufficiency of the tear film challenges the regulatory systems of the ocular surfaces. The reaction of the surfaces includes temporary mechanisms engaged in the preservation of homeostasis. However, strong or persisting challenges can lead to the potential exhaustion of the coping capacity. This again activates the vicious circle with chronic inflammation and autocatalytic deterioration. Hence, the factors challenging the homeostasis should be addressed in time. Amongst them are a varying osmolarity, constant presence of small lesions at the epithelium, acidification, attrition with mechanical irritation, and onset of pain and discomfort. Each of them and, especially when occurring simultaneously, impose stress on the coping mechanisms and lead to a stress response. Many stressors can culminate, leading to an exhaustion of the coping capacity, outrunning normal resilience. Reaching the limits of stress tolerance leads to the manifestation of a lubrication deficiency as the disease we refer to as dry eye disease (DED). To postpone its manifestation, the avoidance or amelioration of stress factors is one key option. In DED, this is the target of lubrication therapy, substituting the missing tear film or its components. The latter options include the management of secondary sequelae such as the inflammation and activation of reparative cascades. Preventive measures include the enhancement in resilience, recovery velocity, and recovery potential. The capacity to handle the external load factors is the key issue. The aim is to guard homeostasis and to prevent intercellular stress responses from being launched, triggering and invigorating the vicious circle. Considering the dilemma of the surface to have to cope with increased time of exposure to stress, with simultaneously decreasing time for cellular recovery, it illustrates the importance of the vicious circle as a hub for ocular surface stress. The resulting imbalance triggers a continuous deterioration of the ocular surface condition. After an initial phase of the reaction and adaption of the ocular surface to the surrounding challenges, the normal coping capacity will be exhausted. This is the time when the integrated stress response (ISR), a protector for cellular survival, will inevitably be activated, and cellular changes such as altered translation and ribosome pausing are initiated. Once activated, this will slow down any recovery, in a phase where apoptosis is imminent. Premature senescence of cells may also occur. The process of prematurization due to permanent stress exposures contributes to the risk for constant deterioration. The illustrated flow of events in the development of DED outlines that the ability to cope, and to recover, has limited resources in the cells at the ocular surface. The reduction in and amelioration of stress hence should be one of the key targets of therapy and begin early. Here, lubrication optimization as well as causal treatment such as the correction of anatomical anomalies (leading to anatomical dry eye) should be a prime intent of any therapy. The features of cellular stress as a key hub for the vicious circle will be outlined and discussed.

Physiological Responses and Salt Tolerance Evaluation of Different Varieties of Bougainvillea under Salt Stress.

Soil salinization significantly impacts the ecological environment and agricultural production, posing a threat to plant growth. Currently, there are over 400 varieties of Bougainvillea with horticultural value internationally. However, research on the differences in salt tolerance among Bougainvillea varieties is still insufficient. Therefore, this study aims to investigate the physiological responses and tolerance differences of various Bougainvillea varieties under different concentrations of salt stress, reveal the effects of salt stress on their growth and physiology, and study the adaptation mechanisms of these varieties related to salt stress. The experimental materials consisted of five varieties of Bougainvillea. Based on the actual salinity concentrations in natural saline-alkali soils, we used a pot-controlled salt method for the experiment, with four treatment concentrations set: 0.0% (w/v) (CK), 0.2% (w/v), 0.4% (w/v), and 0.6% (w/v). After the Bougainvillea plants grew stably, salt stress was applied and the growth, physiology, and salt tolerance of the one-year-old plants were systematically measured and assessed. The key findings were as follows: Salt stress inhibited the growth and biomass of the five varieties of Bougainvillea; the 'Dayezi' variety showed severe salt damage, while the 'Shuihong' variety exhibited minimal response. As the salt concentration and duration of salt stress increase, the trends of the changes in antioxidant enzyme activity and osmotic regulation systems in the leaves of the five Bougainvillea species differ. Membrane permeability and the production of membrane oxidative products showed an upward trend with stress severity. The salt tolerance of the five varieties of Bougainvillea was comprehensively evaluated through principal component analysis. It was found that the 'Shuihong' variety exhibited the highest salt tolerance, followed by the 'Lvyehuanghua', 'Xiaoyezi', 'Tazi', and 'Dayezi' varieties. Therefore, Bougainvillea 'Shuihong', 'Lvyehuanghua', and 'Xiaoyezi' are recommended for extensive cultivation in saline-alkali areas. The investigation focuses primarily on how Bougainvillea varieties respond to salt stress from the perspectives of growth and physiological levels. Future research could explore the molecular mechanisms behind the responses to and tolerance of different Bougainvillea varieties as to salt stress, providing a more comprehensive understanding and basis for practical applications.

Comparison of Domestic and Foreign Accounting Regulatory Systems from the Perspective of China

The purpose of this article is to compare the accounting supervision system of China and other countries, to reveal their characteristics, advantages and shortcomings, and to discuss how to use the international experience to improve China's accounting supervision system. This paper summarizes the basic framework of accounting supervision system at home and abroad. Through comparative analysis, it points out the deficiencies of our country's accounting supervision system and the advantages of foreign systems. In addition, the paper also discusses the common challenges facing the accounting supervision system at home and abroad. Based on the results of comparative analysis, this article puts forward countermeasures and suggestions to improve our accounting supervision system. Through these measures, the aim is to build a more efficient, transparent and adaptable accounting supervision system.

Evaluation of Enzymatic and Non-enzymatic Antioxidant Defense Responses of Durum Wheat (Triticum durum Desf.) in Coping with Boron Stress

Wheat, one of the world's most important agricultural products, plays a vital role in meeting the nutritional needs of our growing global population. However, arid and semi-arid regions face a potential threat from boron (B) toxicity. While boron is an essential nutrient for plant growth and development, its excessive presence can be toxic. It disrupts physiological processes, causing chlorosis and necrosis, ultimately leading to yield loss or plant death. Although B deficiency is a problem in the soils of many countries, Türkiye is one of the few experiencing B toxicity problems in its agricultural areas. This study investigated the physiological and biochemical responses of durum wheat to various B concentrations (0-20 mg L-1) under controlled air-conditioned cabin conditions. Durum wheat exhibited a decrease in chlorophyll content, phenolic content, and antiradical capacity at B doses exceeding 10 mg L-1. However, carotene content increased steadily with increasing B concentrations. The activities of antioxidant enzymes, including superoxide dismutase (SOD), ascorbate peroxidase (APX), and glutathione S-transferase (GST), increased up to a B dose of 15 mg L-1. Catalase (CAT) and glutathione reductase (GR) activities increased up to 10 mg L-1 B dose but decreased at higher B levels. Proline content increased tenfold up to a B dose of 10 mg L-1, indicating an attempt to mitigate stress. Conversely, malondialdehyde (MDA) accumulation increased continuously (approximately 150%) with increasing B doses, suggesting membrane damage. Despite being considered B-sensitive, this study demonstrated that durum wheat can effectively cope with B stress up to a B dose of 10 mg L-1 under controlled conditions. Beyond this threshold, physiological and biochemical changes indicate a decline in stress tolerance. Many osmoregulators, carotenes, alkaloids, flavonoids, tocopherols, phenolic compounds, non-protein amino acids, and several unidentified metabolites are activated to support antioxidant defense. The SOS pathway and the released ROS force gene regulatory systems come into play. Following these, the ROS released in the organism are neutralized, and ionic homeostasis and cellular stress resistance are achieved.

Motivating factors affecting formalization of small informal enterprises: Evidence from an emerging economy

AbstractThis study investigates the motivating factors behind the formalization of small informal enterprises in Bangladesh, an emerging economy, employing the lens of institutional theory. It emphasizes how regulatory structures, normative pressures, and cognitive understandings shape the decisions of SME owners in emerging economies like Bangladesh. A significant portion of small enterprises in Bangladesh remain informal, leading to concerns over economic development, productivity, and efficiency. Informal enterprises often face challenges such as limited access to finance, market entry barriers, and regulatory hurdles. Recognizing the need for formalization, this research aims to understand the drivers behind this transition. A questionnaire survey of 304 informal enterprises reveals that streamlined regulatory systems, particularly one‐stop solutions and simplified registration processes, are primary motivators for formalization. Additionally, flexible collateral requirements for financing and lower levels of technological adoption also significantly influence this transition. These findings contribute to the academic discourse on informal businesses in emerging economies and provide key policy implications for fostering formalization through targeted strategies and policies.

Differential role of negative and positive parenting styles on resting-state brain networks in middle-aged adolescents

Parenting styles encompass negative and positive approaches, potentially affecting adolescents' brain reward and emotion regulation systems. However, the association between parenting style and brain networks remains unknown. This study investigates the link between parenting style and functional connectivity (FC) within the reward and emotion regulation brain networks, using resting-state functional magnetic resonance imaging (rs-fMRI). A total of forty-two middle-aged adolescents (26 males; 16 females) with no neurological or psychiatric symptoms participated in this study. We assessed parenting behaviors and extracted reward/emotion regulation FC from rs-fMRI. We examined the association between FC and parenting style, identified through principal component analysis. Correlation analysis investigated these links while controlling for sex. We delineated both positive (love-autonomy) and negative (hostility-control) parenting styles, accounting for 79 % of the explained variance in parenting behaviors. The negative parenting style displayed connections with FC within the reward system, particularly in the left nucleus accumbens (NAc), showcasing links to multiple frontal regions. Furthermore, it correlated with the social reward network, specifically the insula-NAc FC in bilateral hemispheres. Conversely, the positive parenting style exhibited an association with FC between the hippocampus and right lateral prefrontal cortex. Our findings support negative parenting's association with an immature reward system and suggest positive parenting's potential to enhance emotion regulation in brain function. These observations highlight two distinct parenting styles, including single-parenting behaviors. Thus, we advance understanding of each style's unique contributions to adolescent reward- and emotion regulation-related brain network development.

A series of vectors for inducible gene expression in multidrug-resistant Acinetobacter baumannii.

Clinical isolates of bacterial pathogens often harbor resistance to multiple antibiotics, with Acinetobacter baumannii being a prime example. The drug-resistance phenotypes associated with these pathogens represent a significant hurdle to researchers who wish to study modern isolates due to the limited availability of plasmid tools. Here, we present a series of freely replicating and Tn7-insertion vectors that rely on selectable markers to less frequently encountered antibiotics, apramycin, and hygromycin. We demonstrate the utility of these plasmid tools through a variety of experiments looking at a multidrug-resistant strain of A. baumannii, strain AB5075. Strain AB5075 is an established model strain for present-day A. baumannii, due in part to its genetic tractability and because it is a representative isolate of the globally disseminated multidrug-resistant clade of A. baumannii, global clone 1. In addition to the drug-selection markers facilitating use in strains resistant to more commonly used antibiotics, the vectors allow for controllable expression driven by several regulatory systems, including isopropyl β-D-1-thiogalactopyranoside (IPTG), arabinose, anhydrotetracycline, and toluic acid.

Resistance, regulation, and governmentality: interrogating the defunding of homeopathy in France and England (2000 to 2022)

AbstractThis paper employs a governmentality framework to explore resistance by CAM sceptics to homeopathy’s partial settlement in the public health systems of England and France, resulting in its defunding in both countries in 2018 and 2021, respectively. While partly dependent upon long-standing problematisations (namely, that homeopathy’s ability to heal is unproven, its mechanisms implausible, and its consequences for patients potentially dangerous), the defunding of homeopathy was also driven by the conduct of CAM sceptics, who undermined homeopathy’s position in strikingly different ways in both contexts. This difference, we suggest, is a consequence of the diverging regulatory arrangements surrounding homeopathy (and CAMs more generally) in England and France—and the ambivalent effects of CAM’s regulation. If law and regulation have been a key component of CAM’s integration and (partial) acceptance over the past four decades, the fortunes of homeopathy in England and France highlight their unpredictability as techniques of governmentality: just as the formal regulatory systems in England and France have helped to normalise homeopathy in different ways, they have also incited and galvanised opposition, providing specific anchor-points for resistance by CAM sceptics.

Post-Bariatric Hypoglycemia: an Impaired Metabolic Response to a Meal

Aims/HypothesisPost-bariatric hypoglycemia (PBH) is caused by postprandial hyperinsulinemia, due to anatomical alterations and changes in post-prandial metabolism after bariatric surgery. The mechanisms underlying the failing regulatory and compensatory systems are unclear. In this study, we investigated the differences in post-prandial hormones and metabolic profiles between patients with and without PBH.MethodsWe performed a mixed meal test (MMT) in 63 subjects before and 1 year after Roux-en-Y gastric bypass (RYGB) surgery. Blood was withdrawn at 0, 10, 20, 30, 60, and 120 min after ingestion of a standardized meal. Glucose, insulin, GLP-1, FGF-19, and FGF-21 were measured and untargeted metabolomics analysis was performed on blood plasma to analyze which hormonal and metabolic systems were altered between patients with and without PBH.ResultsOut of 63, a total of 21 subjects (33%) subjects developed PBH (glucose < 3.1 mmol/L) after surgery. Decreased glucose and increased insulin excursions during MMT were seen in PBH (p < 0.05). GLP-1, FGF-19, and FGF-21 were elevated after surgery (p < 0.001), but did not differ between PBH and non-PBH groups. We identified 20 metabolites possibly involved in carbohydrate metabolism which differed between the two groups, including increased carnitine and acylcholines in PBH.ConclusionOverall, 33% of the subjects developed PBH 1 year after RYGB surgery. While GLP-1, FGF-19, and FGF-21 were similar in PBH and non-PBH patients, metabolomics analysis revealed changes in carnitine and acyclcholines that are possibly involved in energy metabolism, which may play a role in the occurrence of PBH.Graphical

Research on the Mechanisms by Which Green Finance Policies Promote Low-Carbon Economic Development

This paper explores the mechanisms by which green finance policies promote low-carbon economic development, analyzing their implementation effects and challenges in China, and proposing corresponding policy recommendations. Green finance, defined as financial activities supporting environmental protection and sustainable development, aims to direct funds towards environmentally friendly and low-carbon projects. It includes green credit, green bonds, green investment funds, and green insurance, and involves providing preferential loans, issuing green bonds, establishing investment funds, and developing insurance products to support green projects and reduce environmental risks. Additional policies such as green incentives, environmental information disclosure, green ratings, and international cooperation further enhance the effectiveness of green finance. The mechanisms by which green finance policies promote low-carbon development include guiding funds to low-carbon industries, optimizing resource allocation, promoting technological innovation, supporting industrial structure transformation, enhancing market competitiveness, and promoting socially responsible investment. Despite significant progress, challenges such as insufficient supply of green finance resources, regional disparities in policy implementation, limited innovation in green finance products, and imperfect information disclosure and regulatory systems remain. The paper concludes with policy recommendations to increase policy support, improve information disclosure and regulatory systems, promote product innovation, strengthen regional coordinated development, and enhance international cooperation.

Research on the Construction and Optimization of Financial Regulatory Systems in Vocational Institutions

Research on the Construction and Optimization of Financial Regulatory Systems in Vocational Institutions

Enhancing portability of trans-ancestral polygenic risk scores through tissue-specific functional genomic data integration.

Portability of trans-ancestral polygenic risk scores is often confounded by differences in linkage disequilibrium and genetic architecture between ancestries. Recent literature has shown that prioritizing GWAS SNPs with functional genomic evidence over strong association signals can improve model portability. We leveraged three RegulomeDB-derived functional regulatory annotations-SURF, TURF, and TLand-to construct polygenic risk models across a set of quantitative and binary traits highlighting functional mutations tagged by trait-associated tissue annotations. Tissue-specific prioritization by TURF and TLand provide a significant improvement in model accuracy over standard polygenic risk score (PRS) models across all traits. We developed the Trans-ancestral Iterative Tissue Refinement (TITR) algorithm to construct PRS models that prioritize functional mutations across multiple trait-implicated tissues. TITR-constructed PRS models show increased predictive accuracy over single tissue prioritization. This indicates our TITR approach captures a more comprehensive view of regulatory systems across implicated tissues that contribute to variance in trait expression.

Pharmaceutical Market Access in Latin America: Analyzing Approval Requirements in Three Key Nations: Ecuador, Dominican Republic and Nicaragua

: This article presents a comprehensive and comparative analysis of the regulatory frameworks governing the approval of pharmaceuticals in the Dominican Republic, Ecuador, and Nicaragua. It delves into the intricate scientific terminology and complex procedures inher-ent in these regulatory systems, shedding light on the demanding requirements that pharmaceu-tical companies must fulfil to secure market access in these countries. Employing a comparative approach, the article explores both the analogy and differences in the approval processes, focus-ing on factors such as safety standards, efficacy assessments, clinical trial prerequisites, post-marketing surveillance, and overall transparency. The findings contribute to a deeper under-standing of the scientific accuracy and ongoing efforts towards regulatory harmonisation within the pharmaceutical industry across these countries. Furthermore, this study aims to define the regulatory requirements for drug approval in the LATAM region, explicitly emphasising the Dominican Republic, Ecuador, and Nicaragua. It provides insights into the current pharmaceuti-cal market landscape in Latin America, compares the regulatory requirements for drug approval in these three countries, and offers guidance on preparing dossiers for obtaining authorisation of pharmaceutical drug products. By examining the similarities and differences in regulatory stand-ards, this article facilitates a comprehensive understanding of the stringency ratios between these countries and assists companies in navigating the specific regulatory landscapes to achieve suc-cessful drug approvals

Occupational Disease in New York State: The Political Economic Context.

In 1987 Landrigan and Markowitz co-authored a report entitled "Occupational Disease in New York State." They found that death and illness from occupational disease were common and that the costs of exposure to hazardous conditions warranted public funding for new occupational health infrastructure in New York State. A recent confirmatory report recognized a wider spectrum of contemporary hazards and emphasized how public health problems connect to work. These reports provide factual snapshots at 2 points in time, but they do not explain nor analyze the changing conditions they describe. Including macro-contexts such as globalization, financialization, and neoliberalism, this article demonstrates several unique occupational safety and health implications by clarifying key themes related to the state's role, especially regulation and healthcare delivery systems. Conclusions directly tie the trajectory of occupational disease to workers' collective ability to confront and roll back neoliberalism while pushing occupational disease out of its medical/science silo.

Improved stability analysis of delayed frequency regulation systems for a cyber-physical microgrid

Improved stability analysis of delayed frequency regulation systems for a cyber-physical microgrid

Development of a Type I-E CRISPR-Based Programmable Repression System for Fine-Tuning Metabolic Flux toward D-Pantothenic Acid in Bacillus subtilis.

The CRISPR-based regulation tools enable fine-tuning of gene transcription, showing potential in areas of biomanufacturing and live therapeutics. However, the cell toxicity and PAM specificity of existing CRISPR-based regulation systems limit their broad application. The development of new and less-toxic CRISPR-controlled expression systems remains highly desirable for expanding the application scope of CRISPR-based tools. Here, we reconstituted the type I CRISPR-Cas system from Escherichia coli to finely tune gene expression in Bacillus subtilis. Through engineering the 5' untranslated region (UTR) of mRNAs of cas genes, we remarkably improved the efficacy of the type I CRISPRi system. The improved type I CRISPRi system was applied in engineering the D-pantothenic acid (DPA)-producing B. subtilis, which was generated by strengthening the metabolic flux toward β-alanine and (R)-pantoate via enhancing expression of key enzymes at both transcriptional and translational levels. Through controlling the expression of pdhA with the CRISPRi system for fine-tuning the metabolic flux toward DPA and the TCA cycle, we elevated the DPA titer to 0.88 g/L in shake flasks and 12.81 g/L in fed-batch fermentations without the addition of the precursor β-alanine. The type I CRISPRi system and the strategy for fine-tuning metabolic flux reported here not only enrich the CRISPR toolbox in B. subtilis and facilitate DPA production through microbial fermentation but also provide a paradigm for programming important organisms to produce value-added chemicals with cheap raw materials.

Identification of alternative splicing regulatory patterns and characteristic splicing factors in heart failure using RNA-seq data and machine learning

Heart failure (HF) represents the advanced stage of several cardiovascular disorders. This study aimed to build an alternative splicing regulatory network and identify potential splicing factors involved in HF utilizing RNA-seq data and machine learning algorithms. We performed bioinformatics analysis on RNA-seq datasets containing samples from HF patients and normal individuals to obtain gene expression matrices and identify differently regulated alternative splicing events in HF. By calculating percent spliced-in (PSI) value, we identified 4055 abnormal alternative splicing events of 3142 genes in HF. These genes were significantly enriched in PPAR signaling, regulation of actin cytoskeleton, and muscle contraction. Interestingly, based on abnormal alternative splicing events, two distinct clusters of HF patients with distinct molecular mechanisms and pathways were identified using unsupervised clustering. Additionally, we built a regulatory network consisting of heart failure-related alternative splicing and splicing factors. Subsequently, we identify 203 HF specific pairs between splicing factors and alternative splicing events. Four splicing factors (RBM5, ZRANB2, HnRNPF, and HnRNPA0) were found using LASSO and SVM-RFE algorithms, their expression patterns were confirmed in two other microarray datasets. Our study clarifies involvement of splicing factors and alternative splicing events in HF by thoroughly analyzing RNA-seq data with machine learning methods. The findings may advance our understanding of the regulatory systems underlying biological processes associated with heart failure by providing candidates for further investigation and markers for diagnostic and therapeutic purposes.