Search results for: transcriptional regulatory systems

Authors: Juliana Lukša, Bazilė Ravoitytė, Elena Servienė, Saulius Serva

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Totiviridae L-A virus is a persistent Saccharomyces cerevisiae dsRNA virus. It encodes the major structural capsid protein Gag and Gag-Pol fusion protein, responsible for virus replication and encapsulation. These features also enable the copying of satellite dsRNAs (called M dsRNAs) encoding a secreted toxin and immunity to it (known as killer toxin). Viral capsid pore presumably functions in nucleotide uptake and viral mRNA release. During cell division, sporogenesis, and cell fusion, the virions remain intracellular and are transferred to daughter cells. By employing high throughput RNA sequencing data analysis, we describe the influence of solely L-A virus on the expression of genes in three different S. cerevisiae hosts. We provide a new perception into Totiviridae L-A virus-related transcriptional regulation, encompassing multiple bioinformatics analyses. Transcriptional responses to L-A infection were similar to those induced upon stress or availability of nutrients. It also delves into the connection between the cell metabolism and L-A virus-conferred demands to the host transcriptome by uncovering host proteins that may be associated with intact virions. To better understand the virus-host interaction, we applied differential proteomic analysis of virus particle-enriched fractions of yeast strains that harboreither complete killer system (L-A-lus and M-2 virus), M-2 depleted orvirus-free. Our analysis resulted in the identification of host proteins, associated with structural proteins of the virus (Gag and Gag-Pol). This research was funded by the European Social Fund under the No.09.3.3-LMT-K-712-19-0157“Development of Competences of Scientists, other Researchers, and Students through Practical Research Activities” measure.

Keywords: totiviridae, killer virus, proteomics, transcriptomics

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Authors: Pedro Paulino

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The majority of the world’s population is already living in urban areas and the urban population is expected to keep increasing in the next decades. This exponential increase in urban population carries with it obvious mobility problems. Not only a new paradigm in the transport sector is needed in order to address these problems; effective regulatory policies to ensure the quality of services, passenger rights, competition between operators and consistency of the entire mobile ecosystem are needed as well. The purpose of this paper is to present the problems the world faces in this sector and contribute to their solution. Indeed, our study concludes that only through the active supervision of the markets and the activity of monitoring the various operators will it be possible to develop a sustainable and efficient transport system which meets the needs of a changing world.

Keywords: mobility, regulation policies, sanctioning powers, sustainable transport

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Authors: Nino Pailodze, Malkhaz Sulashvili, Vladimer Kekenadze, Tea Khutsishvili, Irma Makharashvili, Aleksandre Kekenadze

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In the nearest future among the important problems which Georgia has solve the most important is economic stability, that bases on fiscal policy and the proper definition of the its directions. The main source of the Budget revenue is the national income. The State uses taxes, loans and emission in order to create national income, were the principal weapon are taxes. As well as fiscal function of the fulfillment of the budget, tax systems successfully implement economic and social development and the regulatory functions of foreign economic relations. A tax is a mandatory, unconditional monetary payment to the budget made by a taxpayer in accordance with this Code, based on the necessary, nonequivalent and gratuitous character of the payment. Taxes shall be national and local. National taxes shall be the taxes provided for under this Code, the payment of which is mandatory across the whole territory of Georgia. Local taxes shall be the taxes provided for under this Code, introduced by normative acts of local self-government representative authorities (within marginal rates), the payment of which is mandatory within the territory of the relevant self-governing unit. National taxes have the leading role in tax systems, but also the local taxes have an importance role in tax systems. Exactly in the means of local taxes, the most part of the budget is formatted. National taxes shall be: income tax, profit tax, value added tax (VAT), excise tax, import duty, property tax shall be a local tax The property tax is one of the significant taxes in Georgia. The paper deals with the taxation mechanism that has been operated in Georgia. The above mention has the great influence in financial accounting. While comparing foreign legislation towards Georgian legislation we discuss the opportunity of using their experience. Also, we suggested recommendations in order to improve the tax system in financial accounting. In addition to accounting, which is regulated according the International Accounting Standards we have tax accounting, which is regulated by the Tax Code, various legal orders / regulations of the Minister of Finance. The rules are controlled by the tax authority, Revenue Service. The tax burden from the tax values are directly related to expenditures of the state from the emergence of the first day. Fiscal policy of the state is as well as expenditure of the state and decisions of taxation. In order to get the best and the most effective mobilization of funds, Government’s primary task is to decide the kind of taxation rules. Tax function is to reveal the substance of the act. Taxes have the following functions: distribution or the fiscal function; Control and regulatory functions. Foreign tax systems evolved in the different economic, political and social conditions influence. The tax systems differ greatly from each other: taxes, their structure, typing means, rates, the different levels of fiscal authority, the tax base, the tax sphere of action, the tax breaks.

Keywords: international accounting standards, financial accounting, tax systems, financial obligations

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Authors: I. Diaz Sanchez, I. M. Martinez-Conesa, M. Illueca

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Accounting conservatism is a desirable quality of earnings that is positively associated with the stridency of regulatory and supervisory regimen and high market discipline. But how these three pillars interact each other is the main research question that is not empirically solved. We analyze how regulatory and supervisory regimes interact with the market discipline measures, such as listing status, ownership and market concentration using a sample of 14,651 bank-year observations covering 54 countries over the period 1997-2009. We evidence that regulation a supervision and extend on which they are enforcement is a strong mechanism to achieved accounting conservatism in those countries or situations where the market discipline fails. Generally, the supervisory power reinforces the effect of listing status, ownership and concentration on conservatism, while capital regulatory mitigates the effect of market discipline on conservatism. This paper may contribute to debate about the mechanism introduced by Basel III that strongly increases the regulation, his enforcement, and the supervisory power after long deregulation period. Although Market discipline is relevant to achieve the financial stability, strong Pillar I and II can ensure the quality of the accounting earnings to prevent bank failures.

Keywords: accounting conservatism, bank regulation, bank supervision, loan loss recognition, market discipline

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Authors: Wafula Simon Peter, Kimuli Nabayego Ibtihal, Nabaggala Kimuli Nashua

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The worldwide use of information and communications technology (ICT) equipment and other electronic equipment is growing and consequently, there is a growing amount of equipment that becomes waste after its time in use. This growth is expected to accelerate since equipment lifetime decreases with time and growing consumption. As a result, e-waste is one of the fastest-growing waste streams globally. The United Nations University (UNU) calculates in its second Global E-waste Monitor 44.7 million metric tonnes (Mt) of e-waste were generated globally in 2016. The study population was 80 respondents, from which a sample of 69 respondents was selected using simple and purposive sampling techniques. This research was carried out to investigate the problem of e-waste and come up with a framework to improve e-waste management. The objective of the study was to develop a framework for improving e-waste management at the College of Engineering, Design, Art and Technology (CEDAT). This was achieved by breaking it down into specific objectives, and these included the establishment of the policy and other Regulatory frameworks being used in e-waste management at CEDAT, the determination of the effectiveness of the e-waste management practices at CEDAT, the establishment of the critical challenges constraining e-waste management at the College, development of a framework for e-waste management. The study reviewed the e-waste regulatory framework used at the college and then collected data which was used to come up with a framework. The study also established that weak policy and regulatory framework, lack of proper infrastructure, improper disposal of e-waste and a general lack of awareness of the e-waste and the magnitude of the problem are the critical challenges of e-waste management. In conclusion, the policy and regulatory framework should be revised, localized and strengthened to contextually address the problem. Awareness campaigns, the development of proper infrastructure and extensive research to establish the volumes and magnitude of the problems will come in handy. The study recommends a framework for the improvement of e-waste.

Keywords: e-waste, treatment, disposal, computers, model, management policy and guidelines

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Authors: David Sarpong, Waleed Khursheed, Ernest Danquah, Erin Murphy

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Shigella is a pathogenic bacterium responsible for shigellosis, a severe diarrheal disease that claims the lives of immunocompromised individuals worldwide. To develop therapeutics against this disease, an understanding of the molecular mechanisms underlying the pathogen’s physiology is crucial. Small non-coding RNAs (sRNAs) have emerged as important regulators of bacterial physiology, including as components of toxin-antitoxin systems. In this study, we investigated the role of RyfA in S. flexneri physiology and virulence. RyfA, originally identified as an sRNA in Escherichia coli, is conserved within the Enterobacteriaceae family, including Shigella. Whereas two copies of ryfA are present in S. dysenteriae, all other Shigella species contain only one copy of the gene. Additionally, we identified a putative open reading frame within the RyfA transcript, suggesting that it may be a dual-functioning gene encoding a small protein in addition to its sRNA function. To study ryfA in vitro, we cloned the gene into an inducible plasmid and observed the effect on bacterial growth. Here, we report that RyfA production inhibits the growth of S. flexneri, and this inhibition is dependent on the contained open reading frame. In-silico analyses have revealed the presence of two divergently transcribed sRNAs, RyfB1 and RyfB2, which share nucleotide complementarity with RyfA and thus are predicted to function as anti-toxins. Our data demonstrate that RyfB2 has a stronger antitoxin effect than RyfB1. This regulatory pattern suggests a novel form of a toxin-antitoxin system in which the activity of a single toxin is inhibited to varying degrees by two sRNA antitoxins. Studies are ongoing to investigate the regulatory mechanism(s) of the antitoxin genes, as well as the downstream targets and mechanism of growth inhibition by the RyfA toxin. This study offers distinct insights into the regulatory mechanisms underlying Shigella physiology and may inform the development of new anti-Shigella therapeutics.

Keywords: sRNA, shigella, toxin-antitoxin, Type 1 toxin antitoxin

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Authors: Mohammaad Afzal Khan, Ghazi Abdulmalik Ashoor , Fatimah Alanazi, Talal Shamma, Abdullah Altuhami, Hala Abdalrahman Ahmed, Abdullah Mohammed Assiri, Dieter Clemens Broering

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Microvascular injuries during inflammation are key causes of transplant malfunctioning and permanent failure, which play a major role in the development of chronic rejection of the transplanted organ. Inflammation-induced microvascular loss is a promising area to investigate the decisive roles of regulatory and effector responses. The present study was designed to investigate the impact of IL-10 on immunotolerance, in particular, the microenvironment of the allograft during rejection. Here, we investigated the effects of IL-10 blockade/ reconstitution and serially monitored regulatory T cells (Tregs), graft microvasculature, and airway epithelium in rejecting airway transplants. We demonstrated that the blocking/reconstitution of IL-10 significantly modulates CD4+FOXP3+ Tregs, microvasculature, and airway epithelium during rejection. Our findings further highlighted that blockade of IL-10 upregulated proinflammatory cytokines, IL-2, IL-1β, IFN-γ, IL-15, and IL-23, but suppressed IL-5 secretion during rejection; however, reconstitution of IL-10 significantly upregulated CD4+FOXP3+ Tregs, tissue oxygenation/blood flow and airway repair. Collectively, these findings demonstrate a potential reparative modulation of IL-10 during microvascular and epithelial repair, which could provide a vital therapeutic window to rejecting transplants in clinical practice.

Keywords: interleukin -10, regulatory T cells, allograft rejection, immunotolerance

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Authors: Waqas Shafqat Chattha, Muhammad Iqbal, Amir Shakeel

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Transcriptional factors are proteins that play a vital role in regulating the transcription of target genes in different biological processes and are being widely studied in different plant species. In the current era of genomics, plant genomes sequencing has directed to the genome-wide identification, analyses and categorization of diverse transcription factor families and hence provide key insights into their structural as well as functional diversity. The DNA-binding with One Finger (DOF) proteins belongs to C2-C2-type zinc finger protein family. DOF proteins are plant-specific transcription factors implicated in diverse functions including seed maturation and germination, phytohormone signalling, light-mediated gene regulation, cotton-fiber elongation and responses of the plant to biotic as well as abiotic stresses. In this context, a genome-wide in-silico analysis of DOF TF family in diploid cotton species i.e. Gossypium raimondii has enabled us to identify 55 non-redundant genes encoding DOF proteins renamed as GrDofs (Gossypium raimondii Dof). Gene distribution studies have shown that all of the GrDof genes are unevenly distributed across 12 out of 13 G. raimondii chromosomes. The gene structure analysis illustrated that 34 out of 55 GrDof genes are intron-less while remaining 21 genes have a single intron. Protein sequence-based phylogenetic analysis of putative 55 GrDOFs has divided these proteins into 5 major groups with various paralogous gene pairs. Molecular evolutionary studies aided with the conserved domain as well as gene structure analysis suggested that segmental duplications were the principal contributors for the expansion of Dof genes in G. raimondii.

Keywords: diploid cotton , G. raimondii, phylogenetic analysis, transcription factor

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Authors: P. Asiabi, M. Shahhoseini, R. Favaedi, F. Hassani, N. Nassiri, B. Movaghar, L. Karimian, P. Eftekhariyazdi

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Introduction: Polycystic Ovary Syndrome is a common gynecologic disorder. Many factors including environment, metabolism, hormones and genetics are involved in etiopathogenesis of PCOS. Of genes that have altered expression in human reproductive system disorders are HOX family genes which act as transcription factors in regulation of cell proliferation, differentiation, adhesion and migration. Since recent evidences consider epigenetic factors as causative mechanisms of PCOS, evaluation of association between known epigenetic marks of acetylation/methylation of histone 3 (H3K9ac/me) with regulatory regions of these genes can represent better insight about PCOS. In the current study, cumulus cells (CCs) which have critical roles during folliculogenesis, oocyte maturation, ovulation and fertilization were aimed to monitor epigenetic alterations of HOX genes. Material and methods: CCs were collected from 20 PCOS patients and 20 fertile women (18-36 year) with male infertility problems referred to the Royan Institute to have ICSI under GnRH antagonist protocol. Informed consents were obtained from the participants. Thirty six hours after hCG injection, ovaries were punctured and cumulus oocyte complexes were dissected. Soluble chromatin were extracted from CCs and Chromatin Immune precipitation (ChIP) coupled with Real Time PCR was performed to quantify the epigenetic marks of histone H3K9 acetylation/methylation (H3K9ac/me) on regulatory regions of 15 members of HOX genes from A-D subfamily. Results: Obtained data showed significant increase of H3K9ac epigenetic mark on regulatory regions of HOXA1, HOXB2, HOXC4, HOXD1, HOXD3 and HOXD4 (P < 0.01) and HOXC5 (P < 0.05) and also significant decrease of H3K9ac into regulatory regions of HOXA2, HOXA4, HOXA5, HOXB1 and HOXB5 (P < 0.01) and HOXB3 (P<0.05) in PCOS patients vs. control group. On the other side, there was a significant decrease in incorporation of H3K9me level on regulatory region of HOXA2, HOXA3, HOXA4, HOXA5, HOXB3 and HOXC4 (P≤0.01) and HOXB5 (P < 0.05) in PCOS patients vs. control group. This epigenetic mark (H3K9me2) has significant increase on regulatory region of HOXB1, HOXB2, HOXC5, HOXD1, HOXD3 and HOXD4 (P ≤ 0.01) and HOXB4 (P < 0.05) in patients vs. control group. There were no significant changes in acetylation/methylation levels of H3K9 on regulatory regions of the other studied genes. Conclusion: Current study suggests that epigenetic alterations of HOX genes can be correlated with PCOS and consequently female infertility. This finding might offer additional definitions of PCOS, and eventually provides insight for novel treatments with epidrugs for this disease.

Keywords: epigenetic, HOX genes, PCOS, female infertility

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Authors: Mengjia Zhi, Xingmei Wei, Xiang Gao, Shiyang Liu, Zhiran Huang, Li Yang, Jing Sun

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Background: To understand the consumption trend of opioid analgesics and the consumption adequacy of opioid analgesic treatment for moderate to severe pain in China, as well as the pain control level of China with international perspective. Importance: To author’s best knowledge, this is the first study in China to measure the adequacy of opioid analgesic treatment for moderate to severe pain considering disease pattern and with the standardized pain treatment guideline. Methods: A retrospective analysis was carried out to show the consumption frequency (daily defined doses, DDDs) of opioid analgesics and its trend in China from 2006 to 2016. Adequacy of consumption measure (ACM) was used to measure the number of needed morphine equivalents and the overall adequacy of opioid analgesic treatment of moderate to severe pain in China, and compared with international data. Results: The consumption frequency of opioid analgesics (DDDs) in China increased from 13,200,000 DDDs in 2006 to 44,200,000 DDDs in 2016, and showed an increasing trend. The growth rate was faster at first, especially in 2013, then slowed down, decreased slightly in 2015. The ACM of China increased from 0.0032 in 2006 to 0.0074 in 2016, with an overall trend of growth. The ACM level of China has been always a very poor level during 2006-2016. Conclusion: The consumption of opioid analgesics for the treatment of moderate to severe pain in China has always been inadequate. There is a huge gap between China and the international level. There are many reasons behind this problem, which lie in different aspects, including medical staff, patients and the public, health systems and social & cultural aspects. It is necessary to strengthen the training and education of medical staff and the patients, to use mass media to disseminate scientific knowledge of pain management, to encourage communications between doctors and patients, to improve regulatory system for the controlled medicines and the overall health systems, and to balance the regulatory goal for avoidance of abuse, and the social goal of meeting the increasing needs of the people for better life.

Keywords: opioid analgesics, adequate consumption measure, pain control, China

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Authors: Ivan Poza Martínez

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The international energy landscape has been significantly affected by the Covid-19 pandemic and te conflict in Ukraine. The Vaca Muerta sedimentary formation in Argentina´s Neuquén province has become a crucial area for energy production, specifically in the shale gas ad shale oil sectors. The massive investment required for theexploitation of this reserve make it essential to understand te determinants of the investment in the upstream sector at both local ad international levels. The aim of this study is to identify the qualitative and quantitative determinants of investment in Vaca Muerta. The research methodolody employs both quantiative ( econometrics ) and qualitative approaches. A linear regression model is used to analyze the impact in non-conventional hydrocarbons. The study highlights that, in addition to quantitative factors, qualitative variables, particularly the design of a regulatory framework, significantly influence the level of the investment in Vaca Muerta. The analysis reveals the importance of attracting both domestic and foreign capital investment. This research contributes to understanding the factors influencing investment inthe Vaca Muerta regioncomapred to other published studies. It emphasizes to role of qualitative varibles, such as regulatory frameworks, in the development of the shale gas and oil sectors. The study uses a combination ofquantitative data , such a investment figures, and qualitative data, such a regulatory frameworks. The data is collected from various rpeorts and industry publications. The linear regression model is used to analyze the relationship between the variables and the investment in Vaca Muerta. The research addresses the question of what factors drive investment in the Vaca Muerta region, both from a quantitative and qualitative perspective. The study concludes that a combination of quantitative and qualitative factors, including the design of a regulatory framework, plays a significant role in attracting investment in Vaca Muerta. It highlights the importance of these determinants in the developmentof the local energy sector and the potential economic benefits for Argentina and the Southern Cone region.

Keywords: vaca muerta, FDI, shale gas, shale oil, YPF

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Authors: Ramazan I. Kadiev, Arcady Ponosov

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Mathematical models of gene regulatory networks can in many cases be described by ordinary differential equations with switching nonlinearities, where the initial value problem is ill-posed. Several regularization methods are known in the case of deterministic networks, but the presence of stochastic noise leads to several technical difficulties. In the presentation, it is proposed to apply the methods of the stochastic singular perturbation theory going back to Yu. Kabanov and Yu. Pergamentshchikov. This approach is used to regularize the above ill-posed problem, which, e.g., makes it possible to design stable numerical schemes. Several examples are provided in the presentation, which support the efficiency of the suggested analysis. The method can also be of interest in other fields of biomathematics, where differential equations contain switchings, e.g., in neural field models.

Keywords: ill-posed problems, singular perturbation analysis, stochastic differential equations, switching nonlinearities

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Authors: N. Umasuthan, S. D. N. K. Bathige, W. S. Thulasitha, I. Whang, J. Lee

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The MyD88 is an evolutionarily conserved host-expressed adaptor protein that is essential for proper TLR/ IL1R immune-response signaling. A previously identified complete cDNA (1626 bp) of OfMyD88 comprised an ORF of 867 bp encoding a protein of 288 amino acids (32.9 kDa). The gDNA (3761 bp) of OfMyD88 revealed a quinquepartite genome organization composed of 5 exons (with the sizes of 310, 132, 178, 92 and 155 bp) separated by 4 introns. All the introns displayed splice signals consistent with the consensus GT/AG rule. A bipartite domain structure with two domains namely death domain (24-103) coded by 1st exon, and TIR domain (151-288) coded by last 3 exons were identified through in silico analysis. Moreover, homology modeling of these two domains revealed a similar quaternary folding nature between human and rock bream homologs. A comprehensive comparison of vertebrate MyD88 genes showed that they possess a 5-exonic structure. In this structure, the last three exons were strongly conserved, and this suggests that a rigid structure has been maintained during vertebrate evolution. A cluster of TATA box-like sequences were found 0.25 kb upstream of cDNA starting position. In addition, putative 5'-flanking region of OfMyD88 was predicted to have TFBS implicated with TLR signaling, including copies of NFB1, APRF/ STAT3, Sp1, IRF1 and 2 and Stat1/2. Using qPCR technique, a ubiquitous mRNA expression was detected in liver and blood. Furthermore, a significantly up-regulated transcriptional expression of OfMyD88 was detected in head kidney (12-24 h; >2-fold), spleen (6 h; 1.5-fold), liver (3 h; 1.9-fold) and intestine (24 h; ~2-fold) post-Fla challenge. These data suggest a crucial role for MyD88 in antibacterial immunity of teleosts.

Keywords: MyD88, innate immunity, flagellin, genomic analysis

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Authors: Thelma Maria Melo Pinheiro, Guilherme Raposo Diniz Vieira, Sidney Matos da Silva, Leonardo Mendonça de Oliveira Queiroz, Mateus Sousa Pinheiro, Danyllo Wenceslau de Oliveira Lopes

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The present article has the objective to describe the regulatory impact analysis (RIA) of the contracting efficiency of the Brazilian transmission system usage. This contracting is made by users connected to the main transmission network and is used to guide necessary investments to supply the electrical energy demand. Therefore, an inefficient contracting of this energy amount distorts the real need for grid capacity, affecting the sector planning accuracy and resources optimization. In order to provide this efficiency, the Brazilian Electricity Regulatory Agency (ANEEL) homologated the Normative Resolution (NR) No. 666, from July 23th of 2015, which consolidated the procedures for the contracting of transmission system usage and the contracting efficiency verification. Aiming for a more efficient and rational transmission system contracting, the resolution established economic incentives denominated as Inefficiency installment for excess (IIE) and inefficiency installment for over-contracting (IIOC). The first one, IIE, is verified when the contracted demand exceeds the established regulatory limit; it is applied to consumer units, generators, and distribution companies. The second one, IIOC, is verified when the distributors over-contract their demand. Thus, the establishment of the inefficiency installments IIE and IIOC intends to avoid the agent contract less energy than necessary or more than it is needed. Knowing that RIA evaluates a regulatory intervention to verify if its goals were achieved, the results from the application of the above-mentioned normative resolution to the Brazilian transmission sector were analyzed through indicators that were created for this RIA to evaluate the contracting efficiency transmission system usage, using real data from before and after the homologation of the normative resolution in 2015. For this, indicators were used as the efficiency contracting indicator (ECI), excess of demand indicator (EDI), and over-contracting of demand indicator (ODI). The results demonstrated, through the ECI analysis, a decrease of the contracting efficiency, a behaviour that was happening even before the normative resolution of 2015. On the other side, the EDI showed a considerable decrease in the amount of excess for the distributors and a small reduction for the generators; moreover, the ODI notable decreased, which optimizes the usage of the transmission installations. Hence, with the complete evaluation from the data and indicators, it was possible to conclude that IIE is a relevant incentive for a more efficient contracting, indicating to the agents that their contracting values are not adequate to keep their service provisions for their users. The IIOC also has its relevance, to the point that it shows to the distributors that their contracting values are overestimated.

Keywords: contracting, electricity regulation, evaluation, regulatory impact analysis, transmission power system

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Authors: Jian-Jun Shu

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The statistical properties of CRMs are explored by estimating similar-word set occurrence distribution. It is observed that CRMs tend to have a fat-tail distribution for similar-word set occurrence. Thus, the fat-tail test with two fatness coefficients is proposed to distinguish CRMs from non-CRMs, especially from exons. For the first fatness coefficient, the separation accuracy between CRMs and exons is increased as compared with the existing content-based CRM prediction method – fluffy-tail test. For the second fatness coefficient, the computing time is reduced as compared with fluffy-tail test, making it very suitable for long sequences and large data-base analysis in the post-genome time. Moreover, these indexes may be used to predict the CRMs which have not yet been observed experimentally. This can serve as a valuable filtering process for experiment.

Keywords: statistical approach, transcription factor binding sites, cis-regulatory modules, DNA sequences

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Authors: Jill Round

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In the economic system, the financial sector plays a crucial role as an intermediary between market participants, other financial institutions, and customers. Financial institutions such as banks have to make decisions to satisfy the demands of all the participants by keeping abreast of regulatory change. In recent years, progress has been made regarding frameworks, development of rules, standards, and processes to manage risks in the banking sector. The increasing focus of regulators and policymakers placed on risk management, corporate governance, and the organization’s culture is of special interest as it requires a well-resourced risk controlling function, compliance function, and internal audit function. In the past years, the relevance of these functions that make up the so-called Three Lines of Defense has moved from the backroom to the boardroom. The approach of the model can vary based on the various organizational characteristics. Due to the intense regulatory requirements, organizations operating in the financial sector have more mature models. In less regulated industries there is more cloudiness about what tasks are allocated where. All parties strive to achieve their objectives through the effective management of risks and serve the identical stakeholders. Today, the Three Lines of Defense model is used throughout the world. The research looks at trends and emerging issues in the professions of the Three Lines of Defense within the banking sector. The answers are believed to helping to explain the increasing regulatory requirements for the banking sector. While the number of supervisory practices increases the risk management requirements intensify and demand more regulatory compliance at the same time. The Structural Equation Modeling (SEM) is applied by making use of conducted surveys in the research field. It aims to describe (i) the theoretical model regarding the applicable linearity relationships, (ii) the causal relationship between multiple predictors (exogenous) and multiple dependent variables (endogenous), (iii) taking into consideration the unobservable variables and (iv) the measurement errors. The surveys conducted on the research field suggest that the observable variables are caused by various latent variables. The SEM consists of the 1) measurement model and the 2) structural model. There is a detectable correlation regarding the cause-effect relationship among the performed supervisory practices and the increasing scope of regulation. Supervisory practices reinforce the regulatory density. In the past, controls were placed after supervisory practices were conducted or incidents occurred. In further research, it is of interest to examine, whether risk management is proactive, reactive to incidents and supervisory practices or can be both at the same time.

Keywords: risk management, structural equation model, supervisory practice, three lines of defense

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Authors: Kalbende Krunal Ramesh

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The Carbon Capture and Storage Technology (CCS) provides a veritable platform to bridge the gap between the seemingly irreconcilable twin global challenges of ensuring a secure, reliable and diversified energy supply and mitigating climate change by reducing atmospheric emissions of carbon dioxide. Making its proper regulatory policy and making it flexible for the government and private company by law to regulate, also exploring the opportunity in this sector is the main aim of this paper. India's total annual emissions was 1725 Mt CO2 in 2011, which comprises of 6% of total global emission. It is very important to control the greenhouse gas emission for the environment protection. This paper discusses the various regulatory policy and technology adopted by some of the countries for successful using CCS technology. The brief geology of sedimentary basins in India is studied, ranging from the category I to category IV and deep water and potential for mature technology in CCS is reviewed. Areas not suitable for CO2 storage using presently mature technologies were over viewed. CSS and Clean development mechanism was developed for India, considering the various aspects from research and development, project appraisal, approval and validation, implementation, monitoring and verification, carbon credit issued, cap and trade system and its storage potential. The opportunities in oil and gas operations, power sector, transport sector is discussed briefly.

Keywords: carbon credit issued, cap and trade system, carbon capture and storage technology, greenhouse gas

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Authors: Lateefat Amao, Misagh Faezipour

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Implementing electronic health records (EHR) in healthcare is a pivotal transition aimed at digitizing and optimizing patient health information management. The expectations associated with this transition are high, even towards other health information systems (HIS) and health technology. This multifaceted process involves careful planning and execution to improve the quality and efficiency of patient care, especially as healthcare technology is a sensitive niche. Key considerations include a thorough needs assessment, judicious vendor selection, robust infrastructure development, and training and adaptation of healthcare professionals. Comprehensive training programs, data migration from legacy systems and models, interoperability, as well as security and regulatory compliance are imperative for healthcare staff to navigate EHR systems adeptly. The purpose of this work is to offer a comprehensive review of the literature on EHR implementation. It explores the impact of this health technology on health practices, highlights challenges and barriers to its successful utility, and offers practical strategies that can impact its success in healthcare. This paper provides a thorough review of studies on the adoption of EHRs, emphasizing the wide range of experiences and results connected to EHR use in the medical field, especially across different types of healthcare organizations.

Keywords: healthcare, electronic health records, EHR implementation, patient care, interoperability

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Authors: Ilya B. Tsyrlov, Dmitry Y. Oshchepkov

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A computational search for dioxin response elements (DREs) in genes of proteins comprising the Ah receptor (AhR) cytosolic core complex was performed by highly efficient tool SITECON. Eventually, the following number of new DREs in 5’flanking region was detected by SITECON: one in AHR gene, five in XAP2, eight in HSP90AA1, and three in HSP90AB1 genes. Numerous DREs found in genes of AhR and AhR cytosolic complex members would shed a light on potential mechanisms of expression, the stoichiometry of unliganded AhR core complex, and its degradation vs biosynthesis dynamics resulted from treatment of target cells with the AhR most potent ligand, 2,3,7,8-TCDD. With human viruses, reduced susceptibility to TCDD of geneencoding HIV-1 P247 was justified by the only potential DRE determined in gag gene encoding HIV-1 P24 protein, whereas the regulatory region of CMV genes encoding IE gp/UL37 has five potent DRE, 1.65 kb/UL36 – six DRE, pp65 and pp71 – each has seven DRE, and pp150 – ten DRE. Also, from six to eight DRE were determined with SITECON in the regulatory region of HSV-1 IE genes encoding tegument proteins, UL36 and UL37, and of UL19 gene encoding bindingglycoprotein C (gC). So, TCDD in the low picomolar range may activate in human cells AhR: Arnt transcription pathway that triggers CMV and HSV-1 reactivation by binding to numerous promoter DRE within immediate-early (IE) genes UL37 and UL36, thus committing virus to the lytic cycle.

Keywords: dioxin response elements, Ah receptor, AhR: Arnt transcription pathway, human and viral genes

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Authors: Paulina Pietrzak

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The understanding of the role of the contemporary translator is fraught with contradictions and idealistic visions of individuals who, by definition, should be fully competent and versatile. In spite of the fact that lots of translation researchers have probed into the identification and exploration of the concept of translator competence, little study has been devoted to its metacognitive aspects. Due to the dynamic nature of the translator’s occupation, it is difficult to predict what specific skills will prove useful for novice translators in their professional career. Thus, it is crucial that the translator is self-regulated enough to adapt to changing job demands and effectively function in the contemporary, highly dynamic, translation market. The objective of the presentation is to investigate the role and nature of the translator’s self-regulation. It will also demonstrate the results of a pilot study into translation trainees’ self-regulatory skills and explore implications of these findings for translator training in relation to theories of student empowerment.

Keywords: cognitive translation research, translator competence, self-regulatory skills, translator training

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Authors: Xinxiu Li, Chuqian Zheng, Yanyan Qian, Hong Fan

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Objectives: In hepatocellular carcinoma (HCC), oncogenes are continuously and robustly transcribed due to aberrant expression of essential components of the trans-acting super-enhancers (SE) complex. Preclinical and clinical trials are now being conducted on small-molecule inhibitors that target core-transcriptional components, including as transcriptional bromodomain protein 4 (BRD4) and cyclin-dependent kinase 7 (CDK7), in a number of malignant tumors. This study aims to explore whether co-overexpression of BRD4 and CDK7 is a potential marker of worse prognosis and a combined therapeutic target in HCC. Methods: The expression pattern of BRD4 and CDK7 and their correlation with prognosis in HCC were analyzed by RNA sequencing data and survival data of HCC patients from TCGA and GEO datasets. The protein levels of BRD4 and CDK7 were determined by immunohistochemistry (IHC), and survival data of patients were analyzed using the Kaplan-Meier method. The mRNA expression levels of genes in HCC cell lines were evaluated by quantitative PCR (q-PCR). CCK-8 and colony formation assays were conducted to assess cell proliferation of HCC upon treatment with BRD4 inhibitor JQ1 or/and CDK7 inhibitor THZ1. Results: It was shown that BRD4 and CDK7 were often overexpressed in HCCs and were associated with poor prognosis of HCC by analyzing the TCGA and GEO datasets. BRD4 or CDK7 overexpression was related to a lower survival rate. It's interesting to note that co-overexpression of CDK7 and BRD4 was a worse prognostic factor in HCC. Treatment with JQ1 or THZ1 alone had an inhibitory effect on cell proliferation; however, when JQ1 and THZ1 were combined, there was a more notable suppression of cell growth. At the same time, the combined use of JQ1 and THZ1 synergistically suppresses the expression of HCC driver genes. Conclusion: Our research revealed that BRD4 and CDK7 coupled can be a useful biomarker in HCC prognosis and the combination of JQ1 and THZ1 can be a promising therapeutic therapy against HCC.

Keywords: BRD4, CDK7, cell proliferation, combined inhibition

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Authors: Guldana Zhigerbayeva, Ming Yang

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Transportation of hazardous materials (HAZMAT) is inevitable in the process industries. The statistics show a significant number of accidents has occurred during the transportation of HAZMAT. This makes risk management of HAZMAT transportation an important topic. The tree-based methods including fault-trees, event-trees and cause-consequence analysis, and Bayesian network, have been applied to risk management of HAZMAT transportation. However, there is limited work on the development of a systematic approach. The existing approaches fail to build up the linkages between the regulatory requirements and the safety measures development. The analysis of historical data from the past accidents’ report databases would limit our focus on the specific incidents and their specific causes. Thus, we may overlook some essential elements in risk management, including regulatory compliance, field expert opinions, and suggestions. A systematic approach is needed to translate the regulatory requirements of HAZMAT transportation into specified safety measures (both technical and administrative) to support the risk management process. This study aims to first adapt the House of Quality (HoQ) to House of Safety (HoS) and proposes a new approach- Safety Function Deployment (SFD). The results of SFD will be used in a multi-criteria decision-support system to develop find an optimal route for HazMats transportation. The proposed approach will be demonstrated through a hypothetical transportation case in Kazakhstan.

Keywords: hazardous materials, risk assessment, risk management, quality function deployment

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Authors: Aikaterini Tsalampouni

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The European Union has long been the most developed model of economic and political integration that has brought a common market, a common currency and a standardization of national policies in certain areas in consistent with EU values and principles. To this direction, there is a parallel process of social integration that effect public policy decisions of member states. Even though social policy, i.e. social protection and moreover healthcare policy, still remains in state's responsibility to develop, EU applies different mechanisms in order to influence health policy systems, since from a more federalist point of view, EU ought to expand its regulatory and legislative roles in as many policy areas as possible. Recently, the pandemic has become a turning point for health care provision and at the same time has also highlighted the need to strengthen the EU’s role in coordinating health care. This paper analyses the EU health policy in general, as well as the response to COVID-19 pandemic with an attempt to identify indications of interaction between EU policies and the promotion of sustainable and resilient health systems. More analytically, the paper investigates the EU binding legal instruments, non-binding legal instruments, monitoring and assessment instruments and instruments for co-financing concerning health care provision in member states and records the evolution of health policies before and during the COVID-19 pandemic. The paper concludes by articulating some remarks regarding the improvement of health policy in EU. Since the ability to deal with a pandemic depends on continuous and increased investment in health systems, the involvement of the EU can lead to a policy convergence, necessary for the resilience of the systems, maintaining at the same time, a strong health policy framework in Europe.

Keywords: EU health policy, EU response to COVID-19, European Health Union, health systems in Europe

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Authors: Eugene Stepanov, Arkadi Ponossov

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Ordinary differential equations with switching nonlinearities constitute a very useful tool in many applications. The solutions of such equations can usually be calculated analytically if they cross the discontinuities transversally. Otherwise, one has trajectories that slides along the discontinuity, and the calculations become less straightforward in this case. For instance, one of the problems one faces is non-uniqueness of the sliding modes. In the presentation, it is proposed to apply the theory of hybrid dynamical systems to calculate the solutions that are ‘hidden’ in the discontinuities. Roughly, one equips the underlying switched system with an explicitly designed discrete dynamical system (‘automaton’), which governs the dynamics of the switched system. This construction ‘splits’ the dynamics, which, as it is shown in the presentation, gives uniqueness of the resulting hybrid trajectories and at the same time provides explicit formulae for them. Projecting the hybrid trajectories back onto the original continuous system explains non-uniqueness of its trajectories. The automaton is designed with the help of the attractors of the specially constructed adjoint dynamical system. Several examples are provided in the presentation, which supports the efficiency of the suggested scheme. The method can be of interest in control theory, gene regulatory networks, neural field models and other fields, where switched dynamics is a part of the analysis.

Keywords: hybrid dynamical systems, singular perturbation analysis, sliding modes, switched dynamics

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Authors: Eugene Stepanov, Arcady Ponosov

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To model gene regulatory networks one uses ordinary differential equations with switching nonlinearities, where the initial value problem is known to be well-posed if the trajectories cross the discontinuities transversally. Otherwise, the initial value problem is usually ill-posed, which lead to theoretical and numerical complications. In the presentation, it is proposed to apply the theory of hybrid dynamical systems, rather than switched ones, to regularize the problem. 'Hybridization' of the switched system means that one attaches a dynamic discrete component ('automaton'), which follows the trajectories of the original system and governs its dynamics at the points of ill-posedness of the initial value problem making it well-posed. The construction of the automaton is based on the classification of the attractors of the specially designed adjoint dynamical system. Several examples are provided in the presentation, which support the suggested analysis. The method can also be of interest in other applied fields, where differential equations contain switchings, e.g. in neural field models.

Keywords: hybrid dynamical systems, ill-posed problems, singular perturbation analysis, switching nonlinearities

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Authors: Clara Franch de la Cal, Christopher J Morris, Michael McArthur

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Cystic fibrosis (CF) is an autosomal recessive genetic disorder characterized by abnormal transport of chloride and sodium across the lung epithelium, leading to thick and viscous secretions. Within which CF patients suffer from repeated bacterial pulmonary infections, with Pseudomonas aeru-ginosa (PA) eliciting the greatest inflammatory response, causing an irreversible loss of lung func-tion that determines morbidity and mortality. The cell wall of PA is a permeability barrier to many antibacterials and the rise of Mutli-Drug Resistant strains (MDR) is eroding the efficacy of the few remaining clinical options. In addition when PA infection becomes established it forms an antibi-otic-resistant biofilm, embedded in which are slow growing cells that are refractive to drug treat-ment. Making the development of new antibacterials a major challenge. This work describes the development of new type of nanoparticulate oligonucleotide antibacterial capable of tackling PA infections, including MDR strains. It is being developed to both block growth and prevent biofilm formation. These oligonucleotide therapeutics, Transcription Factor Decoys (TFD), act on novel genomic targets by capturing key regulatory proteins to block essential bacterial genes and defeat infection. They have been successfully transfected into a wide range of pathogenic bacteria, both in vitro and in vivo, using a proprietary delivery technology. The surfactant used self-assembles with TFD to form a nanoparticle stable in biological fluids, which protects the TFD from degradation and preferentially transfects prokaryotic membranes. Key challenges are to adapt the nanoparticle so it is active against PA in the context of biofilms and to formulate it for administration by inhalation. This would allow the drug to be delivered to the respiratory tract, thereby achieving drug concentrations sufficient to eradicate the pathogenic organisms at the site of infection.

Keywords: antibacterials, transcriptional factor decoys (TFDs), pseudomonas aeruginosa

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Authors: Vincent Murray

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The chromatin structure at the transcription start sites (TSSs) of genes is very important in the control of gene expression. In order for gene expression to occur, the chromatin structure at the TSS has to be altered so that the transcriptional machinery can be assembled and RNA transcripts can be produced. In particular, the nucleosome structure and positioning around the TSS has to be changed. Bleomycin is utilized as an anti-tumor agent to treat Hodgkin's lymphoma, squamous cell carcinoma, and testicular cancer. Bleomycin produces DNA damage in human cells and DNA strand breaks, especially double-strand breaks, are thought to be responsible for the cancer chemotherapeutic activity of bleomycin. Bleomycin is a large glycopeptide with molecular weight of approximately 1500 Daltons and hence its DNA strand cleavage activity can be utilized as a probe of chromatin structure. In this project, Illumina next-generation DNA sequencing technology was used to determine the position of DNA double-strand breaks at the TSSs of genes in intact cells. In this genome-wide study, it was found that bleomycin cleavage preferentially occurred at the TSSs of actively transcribed human genes in comparison with non-transcribed genes. There was a correlation between the level of enhanced bleomycin cleavage at TSSs and the degree of transcriptional activity. In addition, bleomycin was able to determine the position of nucleosomes at the TSSs of human genes. Bleomycin analogues were also utilized as probes of chromatin structure at the TSSs of human genes. In a similar manner to bleomycin, the bleomycin analogues 6′-deoxy-BLM Z and zorbamycin preferentially cleaved at the TSSs of human genes. Interestingly this degree of enhanced TSS cleavage inversely correlated with the cytotoxicity (IC50 values) of BLM analogues. This indicated that the degree of cleavage by bleomycin analogues at the TSSs of human genes was very important in the cytotoxicity of bleomycin and analogues. It also provided a deeper insight into the mechanism of action of this cancer chemotherapeutic agent since actively transcribed genes were preferentially targeted.

Keywords: anti-cancer activity, chromatin structure, cytotoxicity, gene expression, next-generation DNA sequencing

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Authors: Laura Mion

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The implementation of quality management systems in higher education in different countries is determined by national regulatory choices and supranational indications (such as the European Standard Guidelines for Quality Assurance). The effective functioning and transformative capacity of these quality management systems largely depend on the organizational context in which they are applied and, more specifically, on the culture of quality developed in single universities or in single countries. The University's concept of quality culture integrates the structural dimension of QA (quality management manuals, process definitions, tools) with the value dimension of an organization (principles, skills, and attitudes). Within the EHEA (European Higher Education Area), countries such as Portugal, the Netherlands, the UK, and Norway demonstrate a greater integration of QA principles in the various organizational levels and areas of competence of university institutions or have greater experience in implementation or scientific and political debate on the matter. Therefore, the study, through an integrative literature review, of the quality management systems of these countries is aimed at determining a framework of the culture of quality, helpful in defining the elements which, both in structural-organizational terms and in terms of values and skills and attitudes, have proved to be factors of success in the effective implementation of quality assurance systems in universities and in the countries considered in the research. In order for a QA system to effectively aim for continuous improvement in a complex and dynamic context such as the university one, it must embrace a holistic vision of quality from an integrative perspective, focusing on the objective of transforming the reality being evaluated.

Keywords: higher education, quality assurance, quality culture, Portugal, Norway, Netherlands, United Kingdom

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Authors: Sarah Marie

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In today's dynamic financial landscape, cryptocurrencies represent a paradigm shift characterized by innovation and intense debate. This study probes into their transformative potential and the challenges they present, offering a balanced perspective that recognizes both their promise and pitfalls. Emulating the engaging style of a TED Talk, this research goes beyond academic analysis, serving as a critical bridge to reconcile the perspectives of cryptocurrency skeptics and enthusiasts, fostering a well-informed dialogue. The study employs a mixed-method approach, analyzing current trends, regulatory landscapes, and public perceptions in the cryptocurrency domain. It distinguishes genuine innovators in this field from ostentatious opportunists, echoing the sentiment that real innovation should be separated from mere showmanship. If one is unfamiliar with who is being referenced, they can likely spot them leaning against their Lamborghinis outside "Crypto" conventions, looking greasy. Major findings reveal a complex scenario dominated by regulatory uncertainties, market volatility, and security issues, emphasizing the need for a coherent regulatory framework that balances innovation with risk management and sustainable practices. The study underscores the importance of transparency and consumer protection in fostering responsible growth within the cryptocurrency ecosystem. In conclusion, the research advocates for education, innovation, and ethical governance in the realm of cryptocurrencies. It calls for collaborative efforts to navigate the intricacies of this evolving landscape and to realize its full potential in a responsible, inclusive, and forward-thinking manner.

Keywords: financial landscape, innovation, public perception, transparency

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Authors: Jasini Waida, Usman Rilwan, S. I. Ikpughul, E. I. Ugwu

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Carcinogenic substances are those that induce tumours (benign or malignant), increase their incidence or malignancy, or shorten the time of tumour occurrence when they get into the body through inhalation, injection, dermal application, or ingestion. Using X-Ray Fluorescence, this study reveals the accumulation of heavy metals in Jos East. The results of this study showed that the Geo-Accumulation Index (Igeo) of water for different heavy metals decreased in the order of Cd (0.15) > Cr and As (0.03) > Pb (-0.13) > Ni (-0.6). The soil content for different heavy metals decreased in the order of As and Cd (0.4) > Ni, Cr and Pb (0.2). The edible plants for different heavy metals decreased in the order of Cd (0.512) > As (0.25) > Pb (0.23) > Ni (0.01) > Ni (-0.06). 21% of these points are uncontaminated, except for a few points that are found within the uncontaminated to moderately contaminated level. It is possible to conclude that the area is uncontaminated to moderately contaminated, necessitating regulation. Hence, this study can be used as reference data for regulatory bodies like the Nigerian Nuclear Regulatory Authority (NNRA) and the rest.

Keywords: heavy metals, soil, plants, water, contamination factor

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