Search results for: transcriptional regulatory systems

Authors: Salwa M. Almomen, Mona A. Almaghrabi, Saja M. Alhabardi, Adel A. Alrwisan

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Background: Hepatotoxicity is a major reason for medication withdrawal from the markets. Unfortunately, serious adverse hepatic effects can occur after marketing with limited indicators during clinical development. Therefore, finding possible predictors for hepatotoxicity might guide the monitoring program of various stakeholders. Methods: We examined the clinical review documents for drugs approved in the US from 2011 to 2016 to evaluate their hepatic safety profile. Predictors: we assessed whether these medications meet Hy’s Law with hepatotoxicity grade ≥ 3, labeled hepatic adverse effects at approval, or accelerated approval status. Outcome: post-marketing regulatory action related to hepatotoxicity, including product withdrawal or updates to warning, precaution, or adverse effects sections. Statistical analysis: drugs were included in the analysis from the time of approval until the end of 2019 or the first post-marketing regulatory action related to hepatotoxicity, whichever occurred first. The hazard ratio (HR) was estimated using Cox-regression analysis. Results: We included 192 medications in the study. We classified 48 drugs as having grade ≥ 3 hepatotoxicities, 43 had accelerated approval status, and 74 had labeled information about hepatotoxicity prior to marketing. The adjusted HRs for post-marketing regulatory action for products with grade ≥ 3 hepatotoxicity was 0.61 (95% confidence interval [CI], 0.17-2.23), 0.92 (95%CI, 0.29-2.93) for a drug approved via accelerated approval program, and was 0.91 (95%CI, 0.33-2.56) for drugs with labeled hepatotoxicity information at approval time. Conclusion: This study does not provide conclusive evidence on the association between post-marketing regulatory action and grade ≥ 3 hepatotoxicity, accelerated approval status, or availability of labeled information at approval due to sampling size and channeling bias.

Keywords: accelerated approvals, hepatic adverse effects, drug-induced liver injury, hepatotoxicity predictors, post-marketing withdrawal

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Authors: Sami Adwan, Alaa Alhaj Ismail, Claudia Girardone

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This paper examines the changes in the value relevance of book value of equity and net income of financial firms over the crisis period. It also examines how these changes vary with three variables, namely, fair value exposure, ownership concentration, and regulatory capital ratios. Using a sample of financial firms operating in the European Economic Area over 2005-2011, our findings suggest that the value relevance of book value of equity increases while that of net income decreases during the financial crisis. We find that more exposure to fair value accounting mitigates the impact of the crisis on the value relevance of book value of equity and net income. We also find that more concentrated ownership appears to have a mitigating impact on the changes in the value relevance of both book value of equity and net income in times of financial crisis. Finally, we find evidence that the level of regulatory capital ratios tends to have an attenuating effect on the changes in the value relevance of net income (but not book value of equity) in times of financial crisis.

Keywords: value relevance, financial crisis, financial firms, fair value, ownership concentration, regulatory capital

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Authors: Mehdi Nasr-Esfahani, Leila Mohammad Bagheri, Ava Nasr-Esfahani

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Root and collar rot disease caused by Phytophthora capsici (Leonian) is one of the most serious diseases in pepper, Capsicum annuum L. In this study, a diverse collection of 37 commercial edible and ornamental pepper genotypes infected with P. capsici were investigated for biomass parameters and enzymatic activity of peroxidase or peroxide reductases (EC), superoxide dismutase (SOD), polyphenol oxidase (PPOs), catalase (CAT) and phenylalanine ammonia-lyase (PAL). Seven candidate DEG genes were also evaluated on resistant and susceptible pepper cultivars, through measuring product formation, using spectrophotometry and real-time polymerase chain reaction. All the five enzymes and seven defense-gene candidates were up-regulated in all inoculated pepper accessions to P. capsici. But, the enzymes and DEG genes were highly expressed in resistant cv. 19OrnP-PBI, 37ChillP-Paleo, and “23CherryP-Orsh". The expression level of enzymes were 1.5 to 5.6-fold higher in the resistant peppers, than the control non-inoculated genotypes. Also, the transcriptional levels of related candidate DEG genes were 3.16 to 5.90-fold higher in the resistant genotypes. There was a direct and high correlation coefficient between resistance, bio-mass parameters, enzymatic activity, and resistance gene expression. The related enzymes and candidate genes expressed herein will provide a basis for further gene cloning and functional verification studies, and also will aid in an understanding of the regulatory mechanism of pepper resistance to P. capsici.

Keywords: AP2/ERF, cDNA, enzymes, MIP gene, q-RTPCR, XLOC

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Authors: G. L. Rithika, Arvind B. S., Akash R., Ananda Vinayak, Hema M. S.

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Cryptocurrencies were first launched in the year 2009 and have been a great asset to own. Cryptocurrencies are a representation of a completely distinct decentralization model for money. They also contribute to the elimination of currency monopolies and the liberation of money from control. The fact that no government agency can determine a coin's value or flow is what cryptocurrency advocates believe makes them safe and secure. The aim of this paper is to analyze the economic implications of cryptocurrency and how it would disrupt traditional financial systems. This paper analyses the growth of Cryptocurrency over the years and the potential threats of cryptocurrency to financial systems. Our analysis shows that although the DeFi design, like the traditional financial system, may have the ability to lower transaction costs, there are multiple layers where rents might build up because of endogenous competition limitations. The permissionless and anonymous design of DeFi poses issues for ensuring tax compliance, anti-money laundering laws and regulations, and preventing financial misconduct.

Keywords: cryptocurrencies, bitcoin, blockchain technology, traditional financial systems, decentralisation, regulatory framework

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Authors: Mark Lokanan

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The paper analyzes the processing of complaints against investment brokers and dealer members through the Investment Industry Regulatory Organization of Canada (IIROC) from 2008 to 2017. IIROC is the self-regulatory organization (SRO) that is responsible for policing investment dealers and brokerage firms that trade in Canada’s securities market. Data from the study came from IIROC's enforcement annual reports for the years examined. The case processing is evaluated base on the misconduct funnel that was originally designed for street crime and applies to the enforcement of investment fraud. The misconduct funnel is used as a framework to examine IIROC’s claim that it brought in more complaints (funnel in) than government regulators and shows how these complaints are funneled out and funneled away as they are processed through IIROC’s enforcement system. The results indicate that IIROC is ineffective in disciplining its members and is unable to handle the more serious quasi-criminal and improper sales practices offenses. It is hard not to see the results of the paper being used by the legislator in Ottawa to show the importance of a federal securities regulatory agency such as the Securities and Exchange Commission (SEC) in the United States.

Keywords: investment fraud, securities regulation, compliance, enforcement

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Authors: Mohamed Aljarallah, Mohamed Nurullah, George Saridakis

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This paper aims and objectives are to investigate how the structural change of the financial regulatory bodies affect the financial supervision and how the regulators can design such a structure with taking into account; the Central Bank, the conduct of business and the prudential regulators, it will also consider looking at the structure of the international regulatory bodies and what barriers are found. There will be five questions to be answered; should conduct of business and prudential regulation be separated? Should the financial supervision and financial stability be separated? Should the financial supervision be under the Central Bank? To what extent the politician should intervene in changing the regulatory and supervisory structure? What should be the regulatory and supervisory structure when there is financial conglomerate? Semi structure interview design will be applied. This research sample selection contains a collective of financial regulators and supervisors from the emerged and emerging countries. Moreover, financial regulators and supervisors must be at a senior level at their organisations. Additionally, senior financial regulators and supervisors would come from different authorities and from around the world. For instance, one of the participants comes from the International Bank Settlements, others come from European Central Bank, and an additional one will come from Hong Kong Monetary Authority and others. Such a variety aims to fulfil the aims and objectives of the research and cover the research questions. The analysis process starts with transcription of the interview, using Nvivo software for coding, applying thematic interview to generate the main themes. The major findings of the study are as follow. First, organisational structure changes quite frequently if the mandates are not clear. Second, measuring structural change is difficult, which makes the whole process unclear. Third, effective coordination and communication are what regulators looking for when they change the structure and that requires; openness, trust, and incentive. In addition to that, issues appear during the event of crisis tend to be the reason why the structure change. Also, the development of the market sometime causes a change in the regulatory structure. And, some structural change occurs simply because of the international trend, fashion, or other countries' experiences. Furthermore, when the top management change the structure tends to change. Moreover, the structure change due to the political change, or politicians try to show they are doing something. Finally, fear of being blamed can be a driver of structural change. In conclusion, this research aims to provide an insight from the senior regulators and supervisors from fifty different countries to have a clear understanding of why the regulatory structure keeps changing from time to time through a qualitative approach, namely, semi-structure interview.

Keywords: financial regulation bodies, financial regulatory structure, global financial regulation, financial crisis

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Authors: Fady Tawakol

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BitCoin is a decentralized cryptocurrency that can be used without the need of traditional central banks to accomplish any e-commerce trade. The use of such currency could facilitate new economic interactions and linkages. However, without effective and efficient regulations, cryptocurrency transactions are mostly used by criminals to commit crimes such as money laundering, theft, and blackmailing. And because law is one step behind technological developments, this paper discusses the importance of regulations and supervision for the BitCoin-system, to provide unified regulatory solutions for our digital future in the Middle East. It will provide a detailed analysis of the legal nature of BitCoin along with, its regulation with respect to criminal and civil law.

Keywords: BitCoin, financial protection, crypto currency, money laundering

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Authors: Andrew Thayer, Courtney Rondeau, Paraskevi Papadopoulou

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The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) gene-editing technologies have generated considerable discussion about the applications and ethics of their use. However, no consistent guidelines for using CRISPR technologies have been developed -nor common legislation passed related to gene editing, especially as it is connected to genetically modified organisms (GMOs) in the European Union. The recent announcement that the first babies with CRISPR-edited genes were born, along with new studies exploring CRISPR’s applications in treating thalassemia, sickle-cell anemia, cancer, and certain forms of blindness, have demonstrated that the technology is developing faster than the policies needed to control it. Therefore, it can be seen that a reasonable and coherent regulatory framework for the use of CRISPR in human somatic and germline cells is necessary to ensure the ethical use of the technology in future years. The European Union serves as a unique region of interconnected countries without a standard set of regulations or legislation for CRISPR gene-editing. We posit that the EU would serve as a suitable model in comparing the legislations of its affiliated countries in order to understand the practicality and effectiveness of adopting majority-approved practices. Additionally, we present a proposed set of guidelines which could serve as a basis in developing a consistent regulatory framework for the EU countries to implement but also act as a good example for other countries to adhere to. Finally, an additional, multidimensional framework of smart solutions is proposed with which all stakeholders are engaged to become better-informed citizens.

Keywords: CRISPR, ethics, regulatory framework, European legislation

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Authors: Sharon Yunger, Liat Altman, Yuval Garini, Yaron Shav-Tal

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Understanding the dynamics of transcription in living cells has improved since the development of quantitative fluorescence-based imaging techniques. We established a method for following transcription from a single copy gene in living cells. A gene tagged with MS2 repeats, used for mRNA tagging, in its 3' UTR was integrated into a single genomic locus. The actively transcribing gene was detected and analyzed by fluorescence in situ hybridization (FISH) and live-cell imaging. Several cell clones were created that differed in the promoter regulating the gene. Thus, comparative analysis could be obtained without the risk of different position effects at each integration site. Cells in S/G2 phases could be detected exhibiting two adjacent transcription sites on sister chromatids. A sharp reduction in the transcription levels was observed as cells progressed along the cell cycle. We hypothesized that a change in chromatin structure acts as a general mechanism during the cell cycle leading to down-regulation in the activity of some genes. We addressed this question by treating the cells with chromatin decondensing agents. Quantifying and imaging the treated cells suggests that chromatin structure plays a role both in regulating transcriptional levels along the cell cycle, as well as in limiting an active gene from reaching its maximum transcription potential at any given time. These results contribute to understanding the role of chromatin as a regulator of gene expression.

Keywords: cell cycle, living cells, nucleus, transcription

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Authors: Peaceman Sopazi, Mabila Mathebula, John Smallwood

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Recent health and safety (H&S) concerns and their resultant impact on railway operations, namely, the severe acute respiratory syndrome (SARS) or collectively known as SARS-CoV-2 (Covid-19) pandemic and the Fourth Industrial Revolution (4IR), which have dominated public discourse, brought into question as to whether, or not, some aspects of how we have so far managed safety oversight as railway regulatory bodies and operators will remain relevant in a changing railway environment. Railway practitioners have generally found themselves between a proverbial rock and a hard place by being confronted by emerging challenges which have brought along great opportunities for sustainability. As witnesses and participants to the progressively introduced railway safety management, and transformation regimes, this paper attempts to share gathered field experience on adaptable regulatory oversight and safety awareness. The discourse is approached from a South African context but also with an informed perspective of what seems to work and what usually does not. The authors share their own multi and transdisciplinary experience coupled with insights they have gained as researchers of global trends in general safety management and specific aspects of railway safety management, for sustainability. In addition to sharing a largely experience-based methodology for survival, suggestions are offered for consideration as a way of keeping the railway safety management discourse alive as practitioners navigate a new path which is shrouded in a cloud of untold uncertainty. The authors further believe that the right timing for the implementation of the proposed suggestions in this paper will produce beneficial outcomes. Finally, the paper will identify areas that are still open for further investigation for and by researchers and practitioners alike.

Keywords: health & safety management, safety awareness, railway safety management, railway systems sustainability

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Authors: Razieh Zarei, Hassan zm, Abolghasem Ajami, Darush Moslemi, Narges Afsary, Amrollah Mostafa-zade

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Introduction: IL-23 is responsible for the differentiation and expansion of Th17/ThIL-17 cells from naive CD4+ T cells. Therefore, may be IL-23/IL17 axis involve in a variety of allergic and autoimmune diseases, such as RA, MS, inflammatory bowel disease (IBD), and asthma. TGF-β is also share for the differentiation Th17 producing IL-17 and CD4+CD25+Foxp3hiT regulatory cells from naïve CD4+ T cells which are involved in the regulation of immune response, maintaining immunological self-tolerance and immune homeostasis ,and the control of autoimmunity and cancer surveillance. Therefore, T regulatory cells play a key role in autoimmunity, allergy, cancer, infectious disease, and the induction of transplantation tolerance. Vitamin A and it's derivatives (retinoids) inhibit or reverse the carcinogenic process in some types of cancers in oral cavity,head and neck, breast, skin, liver, and blood cells. Shark is a murine organism and its cartilage has antitumor peptides to prevent angiogenesis, in vitro. Our purpose is whether simultaneous oral treatment vitamin A and shark cartilage can modulate IL-23/IL-17 and CD4CD25Foxp3 T regulatory cell/TGF-β pathways and Th1/Th2 immunity in patients with gastric cancer. Materials and Methods: First investigated an imbalanced supernatant of cytokines exist in patients with gastric cancer by ELISA. Associated with cytokines measuring such as IL-23,IL-17,TGF-β,IL-4 and γ-IFN, then flow cytometry was employed to determine whether the peripheral blood mononuclear cells such as CD4+CD25+Foxp3highT regulatory cells in patients with gastric cancer were changed correspondingly. Results: An imbalance between IL-17 secretion and TGF-β/Foxp3 t regulatory cell pathway and so, Th1 immunity (γ-IFN production) and TH2 immunity (IL-4 secretion) was not seen in patients with gastric cancer treated by vitamin A and shark cartilage. But, the simultaneously presented down-regulation of IL-23 indicated, at least cytokine level. Conclusion: Il-23, as a pro-angiogenesis cytokine, probably, help to tumor growth. Hence, suggested that down-regulation of IL-23, at least cytokine level, is useful for anti-tumor immune responses in patients with gastric cancer.

Keywords: IL-23/IL17 axis, TGF-β/CD4CD25Foxp3 T regulatory pathway, γ-IFN, IL-4, shark cartilage and gastric cancer

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Authors: Fatimah Opebiyi

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Economic growth promotion, inflation reduction and consumer protection are among the core public interest aims of governments. Nevertheless, higher rates of default by consumers in relation to credit card loans and mortgages in recent times illustrate that government’s performance in balancing the protection of the economy and consumer is subpar. This thereby raises an important question on the role of government in protecting consumers during prolonged spells of inflation, particularly when such inflationary trends may be traceable to the acts of the government. Adopting a doctrinal research methodology, this article investigates the evolution of the concept of consumer protection in the United Kingdom and also brings to the fore the tensions and conflicts of interests in the aims and practices of the main regulators within the financial services industry. Relying on public interest theories of regulation and responsive regulatory theory, the article explores the limitations in the state’s ability to strike the right balance in meeting regulatory aims of the regulatory agencies at the opposite ends of the spectrum.

Keywords: financial regulation, consumer protection, prudential regulation, public interest theories of regulation, central bank

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Authors: Qingxin Chen, Liben Jiang, Andrew Smith, Karim Hadjri

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Since 2007, the Chinese food industry has undergone serious food contamination in the baby dairy industry, especially milk powder contamination. One of the milk powder products was found to contain melamine and a significant number (294,000) of babies were affected by kidney stones. Due to growing concerns among consumers about food safety and protection, and high pressure from central government, companies must take radical action to ensure food quality protection through the use of an appropriate quality management system. Previously, though researchers have investigated the health and safety aspects of food industries and products, quality issues concerning food products in China have been largely over-looked. Issues associated with baby dairy products and their quality issues have not been discussed in depth. This paper investigates the impact of quality management systems on the Chinese baby dairy product industry. A literature review was carried out to analyse the use of quality management systems within the Chinese milk power market. Moreover, quality concepts, relevant standards, laws, regulations and special issues (such as Melamine, Flavacin M1 contamination) have been analysed in detail. A qualitative research approach is employed, whereby preliminary analysis was conducted by interview, and data analysis based on interview responses from four selected Chinese baby dairy product companies was carried out. Through the analysis of literature review and data findings, it has been revealed that for quality management system that has been designed by many practitioners, many theories, models, conceptualisation, and systems are present. These standards and procedures should be followed in order to provide quality products to consumers, but the implementation is lacking in the Chinese baby dairy industry. Quality management systems have been applied by the selected companies but the implementation still needs improvement. For instance, the companies have to take measures to improve their processes and procedures with relevant standards. The government need to make more interventions and take a greater supervisory role in the production process. In general, this research presents implications for the regulatory bodies, Chinese Government and dairy food companies. There are food safety laws prevalent in China but they have not been widely practiced by companies. Regulatory bodies must take a greater role in ensuring compliance with laws and regulations. The Chinese government must also play a special role in urging companies to implement relevant quality control processes. The baby dairy companies not only have to accept the interventions from the regulatory bodies and government, they also need to ensure that production, storage, distribution and other processes will follow the relevant rules and standards.

Keywords: baby dairy product, food quality, milk powder contamination, quality management system

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Authors: Raphaël Weuts, Mykyta Petik, Anton Vedder

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Artificial Intelligence has the potential to create and already creates enormous value in healthcare. Prescriptive systems might be able to make the use of healthcare capacity more efficient. Such systems might entail interpretations that exclude the effect of confounders that brings risks with it. Those risks might be mitigated by regulation that prevents systems entailing such risks to come to market. One modality of regulation is that of legislation, and the European AI Act is an example of such a regulatory instrument that might mitigate these risks. To assess the risk mitigation potential of the AI Act for those risks, this research focusses on a case study of a hypothetical application of medical device software that entails the aforementioned risks. The AI Act refers to the harmonised norms for already existing legislation, here being the European medical device regulation. The issue at hand is a causal link between a confounder and the value the algorithm optimises for by proxy. The research identifies where the AI Act already looks at confounders (i.a. feedback loops in systems that continue to learn after being placed on the market). The research identifies where the current proposal by parliament leaves legal uncertainty on the necessity to check for confounders that do not influence the input of the system, when the system does not continue to learn after being placed on the market. The authors propose an amendment to article 15 of the AI Act that would require high-risk systems to be developed in such a way as to mitigate risks from those aforementioned confounders.

Keywords: AI Act, healthcare, confounders, risks

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Authors: Ezra Kavana

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This article analyses the role those East African countries play in enforcing crude oil pipeline regulations. The paper finds that countries are more likely to have responsibility for enforcing these regulations if they have larger networks of gathering and transmission lines and if their citizens are more liberal and more pro-environment., Pipeline operations, transportation costs, new pipeline construction, and environmental effects are all heavily controlled. All facets of pipeline systems and the facilities connected to them are governed by statutory bodies. In order to support the project manager on such new pipeline projects, companies building and running these pipelines typically include personnel and consultants who specialize in these permitting processes. The primary permissions that can be necessary for pipelines carrying different commodities are mentioned in this paper. National, regional, and local municipalities each have their own permits. Through their right-of-way group, the contractor's project compliance leadership is typically directly responsible for obtaining those permits, which are typically obtained through government agencies. The whole list of local permits needed for a planned pipeline can only be found after a careful field investigation. A country's government regulates pipelines that are entirely within its borders. With a few exceptions, state regulations governing ratemaking and safety have been enacted to be consistent with regulatory requirements. Countries that produce a lot of energy are typically more involved in regulating pipelines than countries that produce little to no energy. To identify the proper regulatory authority, it is important to research the several government agencies that regulate pipeline transportation. Additionally, it's crucial that the scope determination of a planned project engage with a various external professional with experience in linear facilities or the company's pipeline construction and environmental professional to identify and obtain any necessary design clearances, permits, or approvals. These professionals can offer precise estimations of the costs and length of time needed to process necessary permits. Governments with a stronger energy sector, on the other hand, are less likely to take on control. However, the performance of the pipeline or national enforcement activities are unaffected significantly by whether a government has taken on control. Financial fines are the most efficient government enforcement instrument because they greatly reduce occurrences and property damage.

Keywords: crude oil, pipeline, regulatory compliance, and construction permits

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Authors: Meysam Saidi

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While the specific externalities and required regulatory measures in relation to Islamic banking are fairly uncertain, the business is growing across the world. Unofficial data indicate that the Islamic Finance market is growing with annual rate of 15% and it has reached 1.3 $ trillion size. This trend is associated with inherent systematic connection of Islamic financial institutions to other entities and different sectors of economies. Islamic banking has been subject of market development policies in major economies, most notably the UK. This trend highlights the need for identification of distinct risk features of Islamic banking and crafting customized regulatory measures. So far there has not been a significant systemic crisis in this market which can be attributed to its distinct nature. However, the significant growth and spread of its products worldwide necessitate an in depth study of its nature for customized congruent regulatory measures. In the post financial crisis era some market analysis and reports suggested that the Islamic banks fairly weathered the crisis. As far as heavily blamed conventional financial products such as subprime mortgage backed securities and speculative credit default swaps were concerned the immunity claim can be considered true, as Islamic financial institutions were not directly exposed to such products. Nevertheless, similar to the experience of the conventional banking industry, it can be only a matter of time for Islamic banks to face failures that can be specific to the nature of their business. Using the experience of conventional banking regulations and identifying those peculiarities of Islamic banking that need customized regulatory approach can aid to prevent major failures. Frank Knight has stated that “We perceive the world before we react to it, and we react not to what we perceive, but always to what we infer”. The debate over congruent Islamic banking regulations might not be an exception to Frank Knight’s statement but I will try to base my discussion on concrete evidences. This paper first analyzes both theoretical and actual features of Islamic banking in order to ascertain to its peculiarities in terms of market stability and other externalities. Next, the paper discusses distinct features of Islamic financial transactions and banking which might require customized regulatory measures. Finally, the paper explores how a more transparent path for the Islamic banking regulations can be drawn.

Keywords: Islamic banking, regulation, risks, capital requirements, customer protection, financial stability

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Authors: Jiandong Ren, Lijun Zhao, Peng Chen

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Nafamostat (NA), a synthetic broad-spectrum serine protease inhibitor, has been routinely employed for the treatment of acute pancreatitis (AP) and other inflammatory-associated diseases in some East Asia countries. Although the potent inhibitory activity against inflammation-related proteases such as thrombin, trypsin, kallikrein, plasmin, coagulation factors and complement factors is generally considered to be responsible for the anti-inflammatory effects of NA, precise target and molecular mechanism underlying the anti-inflammatory activity in the treatment of AP remain largely unknown yet. As an intracellular inflammatory signaling platform, the NOD-like receptor protein 3 (NLRP3) inflammasome is recently identified to be involved in the development of AP. In present study, we have revealed that NA alleviated pancreatic injury in a caerulein-induced AP model by inhibiting the NLRP3 inflammasome activation in pancreas. Mechanistically, NA interacted with HDAC6, a cytoplasmic deacetylase implicated in the NLRP3 inflammasome pathway, and efficiently abrogated the function of HDAC6. This property enabled NA to influence HDAC6 dependent NF-κB transcriptional activity and thus block NF-κB-driven transcriptional priming of NLRP3 inflammasome. Moreover, NA exerted the potential to interfere HDAC6-mediated intracellular transport of NLRP3, thereby leading to the failure of NLRP3 inflammasome activation. Our current work has provided valuable insight into the molecular mechanism underlying the immunomodulatory effect of NA in treatment of AP, highlighting its promising application in prevention of NLRP3 inflammasome-associated inflammatory pathological damage.

Keywords: acute pancreatitis, HDAC6, nafamostat, NLRP3 inflammasome

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Authors: V. Petkova, V. Valchanova, D. Grekova, K. Andreevska, S. T. Geurguiev, V. Madgarov, D. Grekov

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Introduction: Production, distribution and sale of cosmetics is a global industry, which played a key role in the European Union (EU), the US and Japan. A major participant EU whose market cosmetics is greater than in the US and 2 times greater than that in Japan. The output value of the cosmetics industry in the EU is estimated at about € 35 billion in 2001. Nearly 5 billion cosmetic products (number of packages) are sold annually in the EU, and the main markets are France, Germany, Italy, Spain and the UK. The aim of the study is legal and marketing analysis of cosmetic products dispensed in a pharmacy. Materials and methodology: Historical legislative analysis - the method is applied in the analysis of changes in the legislative regulation of the activities of cosmetic products in Japan and Bulgaria Comparative legislative analysis - the method is applied when comparing the legislative requirements for cosmetic products in the already mentioned countries. Both methods are applied to the following regulations: 1) Japanese Pharmaceuticals Affairs Law, Tokyo, Japan, Ministry of Health, Labour and Welfare; 2) Law on Medicinal Products for Human Use; effective from 3.01.2014. Results: The legislative framework for cosmetic products in Bulgaria and Japan is close and generally includes general guidelines: Definition of a medicinal product; Categorization of drugs (with differences in sub-categories); Pre-registration and marketing approval of the competent authorities; Compulsory compliance with gmp (unlike cosmetics); Regulatory focus on product quality, efficacy and safety; Obligations for labeling of such products; Created systems Pharmacovigilance and commitment of all parties - industry and health professionals; The main similarities in the regulation of products classified as cosmetics are in the following segments: Full producer responsibility for product safety; Surveillance of market regulatory authorities; No need for pre-registration or pre-marketing approval (a basic requirement for notification); Without restrictions on sales channels; GMP manuals for cosmetics; Regulatory focus on product safety (than over efficiency); General requirements in labeling: The main differences in the regulation of products classified as cosmetics are in the following segments: Details in the regulation of cosmetic products; Future convergence of regulatory frameworks can contribute to the removal of barriers to trade, to encourage innovation, while simultaneously ensuring a high level of protection of consumer safety.

Keywords: cosmetics, legislation, comparative analysis, Bulgaria, Japan

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Authors: M. Macchiaroli, L. Dolores, V. Pellecchia

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With the recent Resolution n. 580/2019/R/idr, the Italian Regulatory Authority for Energy, Networks, and Environment (ARERA) for the Urban Water Management has introduced, for water managements characterized by persistent critical issues regarding the planning and organization of the service and the implementation of the necessary interventions for the improvement of infrastructures and management quality, a new mechanism for determining tariffs: the regulatory scheme of Convergence. The aim of this regulatory scheme is the overcoming of the Water Service Divided in order to improve the stability of the local institutional structures, technical quality, contractual quality, as well as in order to guarantee transparency elements for Users of the Service. Convergence scheme presupposes the identification of the cost items to be considered in the tariff in parametric terms, distinguishing three possible cases according to the type of historical data available to the Manager. The study, in particular, focuses on operations that have neither data on tariff revenues nor data on operating costs. In this case, the Manager's Constraint on Revenues (VRG) is estimated on the basis of a reference benchmark and becomes the starting point for defining the structure of the tariff classes, in compliance with the TICSI provisions (Integrated Text for tariff classes, ARERA's Resolution n. 665/2017/R/idr). The proposed model implements the recent studies on optimization models for the definition of tariff classes in compliance with the constraints dictated by TICSI in the application of the Convergence mechanism, proposing itself as a support tool for the Managers and the local water regulatory Authority in the decision-making process.

Keywords: decision-making process, economic evaluation of projects, optimizing tools, urban water management, water tariff

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Authors: Chandra Mukherjee

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The prevalent knowledge of the biological systems is based on the standard scientific perception of natural equilibrium, determination and predictability. Recently, a rethinking of concepts was presented and a new scientific perspective emerged that involves complexity theory with deterministic chaos theory, nonlinear dynamics and theory of fractals. The unpredictability of the chaotic processes probably would change our understanding of diseases and their management. The mathematical definition of chaos is defined by deterministic behavior with irregular patterns that obey mathematical equations which are critically dependent on initial conditions. The chaos theory is the branch of sciences with an interest in nonlinear dynamics, fractals, bifurcations, periodic oscillations and complexity. Recently, the biomedical interest for this scientific field made these mathematical concepts available to medical researchers and practitioners. Any biological network system is considered to have a nominal state, which is recognized as a homeostatic state. In reality, the different physiological systems are not under normal conditions in a stable state of homeostatic balance, but they are in a dynamically stable state with a chaotic behavior and complexity. Biological systems like heart rhythm and brain electrical activity are dynamical systems that can be classified as chaotic systems with sensitive dependence on initial conditions. In biological systems, the state of a disease is characterized by a loss of the complexity and chaotic behavior, and by the presence of pathological periodicity and regulatory behavior. The failure or the collapse of nonlinear dynamics is an indication of disease rather than a characteristic of health.

Keywords: HRV, HRVI, LF, HF, DII

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Authors: Ali Alshamrani

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This article aims to give a comprehensive and critical review of sukuk issuance in Saudi Arabia, and the extent to which the issuance of sukuk in Saudi Arabia is consistent with Shariah requirements. The article is divided into two sections. Accordingly, the first section of this article begins with an examination of sukuk in general, and includes the concept of sukuk, the basic principles of sukuk, common types of sukuk, and a critical analysis of the most important differences between sukuk and conventional bonds. The second section gives a critical analysis of how sukuk work in Saudi Arabia, offering the regulatory framework of the issuance of sukuk in the KSA, and the legal challenges from Shariah point of view, and provide recommendations to overcome these challenges.

Keywords: sukuk issuance, Shariah, Saudi Arabia, capital market authority

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Authors: Abderrahim El Maslouhi

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The paper aims to analyze an often-overlooked dimension of global constitutionalism, which is the rise of the regulatory state and its impact on parliamentary dynamics in transition regimes. In contrast to Majone’s technocratic vision of convergence towards a single regulatory system based on competence and efficiency, national transpositions of regulatory governance and, in general, the relationship to global standards primarily depend upon a number of distinctive parameters. These include policy formation process, speed of change, depth of parliamentary tradition and greater or lesser vulnerability to the normative conditionality of donors, interstate groupings and transnational regulatory bodies. Based on a comparison between three post-Arab Spring countries -Morocco, Tunisia, and Egypt, whose constitutions have undergone substantive review in the period 2011-2014- and some European Union state members, the paper intends, first, to assess the degree of permeability to global constitutionalism in different contexts. A noteworthy divide emerges from this comparison. Whereas European constitutions still seem impervious to the lexicon of global constitutionalism, the influence of the latter is obvious in the recently drafted constitutions in Morocco, Tunisia, and Egypt. This is evidenced by their reference to notions such as ‘governance’, ‘regulators’, ‘accountability’, ‘transparency’, ‘civil society’, and ‘participatory democracy’. Second, the study will provide a contextual account of internal and external rationales underlying the constitutionalization of regulatory governance in the cases examined. Unlike European constitutionalism, where parliamentarism and the tradition of representative government function as a structural mechanism that moderates the de-parliamentarization effect induced by global constitutionalism, Arab constitutional transitions have led to a paradoxical situation; contrary to the public demands for further parliamentarization, the 2011 constitution-makers have opted for a de-parliamentarization pattern. This is particularly reflected in the procedures established by constitutions and regular legislation, to handle the interaction between lawmakers and regulatory bodies. Once the ‘constitutional’ and ‘independent’ nature of these agencies is formally endorsed, the birth of these ‘fourth power’ entities, which are neither elected nor directly responsible to elected officials, will raise the question of their accountability. Third, the paper shows that, even in the three selected countries, the de-parliamentarization intensity is significantly variable. By contrast to the radical stance of the Moroccan and Egyptian constituents who have shown greater concern to shield regulatory bodies from legislatures’ scrutiny, the Tunisian case indicates a certain tendency to provide lawmakers with some essential control instruments (e. g. exclusive appointment power, adversarial discussion of regulators’ annual reports, dismissal power, later held unconstitutional). In sum, the comparison reveals that the transposition of the regulatory state model and, more generally, sensitivity to the legal implications of global conditionality essentially relies on the evolution of real-world power relations at both national and international levels.

Keywords: Arab legislatures, de-parliamentarization, global constitutionalism, normative conditionality, regulatory state

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Authors: Chang-Hui Shen, Michelle Esposito, Andrew J. Shen, Michael Adejokun, Diana Laterman

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The packaging of DNA into nucleosomes is critical to genomic compaction, yet it can leave gene promoters inaccessible to activator proteins or transcription machinery and thus prevents transcriptional initiation. Both chromatin remodelers and histone acetylases (HATs) are the two main transcription co-activators that can reconfigure chromatin structure for transcriptional activation. Ino80p is the core component of the INO80 remodeling complex. Recently, it was shown that Ino80p dissociates from the yeast INO1 promoter after induction. However, when certain HATs were deleted or mutated, Ino80p accumulated at the promoters during gene activation. This suggests a link between HATs’ presence and Ino80p’s dissociation. However, it has yet to be demonstrated that Ino80p can be acetylated. To determine if Ino80p can be acetylated, wild-type Saccharomyces cerevisiae cells carrying Ino80p engineered with a double FLAG tag (MATa INO80-FLAG his3∆200 leu2∆0 met15∆0 trp1∆63 ura3∆0) were grown to mid log phase, as were non-tagged wild type (WT) (MATa his3∆200 leu2∆0 met15∆0 trp1∆63 ura3∆0) and ino80∆ (MATa ino80∆::TRP1 his3∆200 leu2∆0 met15∆0 trp1∆63 ura3∆0) cells as controls. Cells were harvested, and the cell lysates were subjected to immunoprecipitation (IP) with α-FLAG resin to isolate Ino80p. These eluted IP samples were subjected to SDS-PAGE and Western blot analysis. Subsequently, the blots were probed with the α-FLAG and α-acetyl lysine antibodies, respectively. For the blot probed with α-FLAG, one prominent band was shown in the INO80-FLAG cells, but no band was detected in the IP samples from the WT and ino80∆ cells. For the blot probed with the α-acetyl lysine antibody, we detected acetylated Ino80p in the INO80-FLAG strain while no bands were observed in the control strains. As such, our results showed that Ino80p can be acetylated. This acetylation can explain the co-activator’s recruitment patterns observed in current gene activation models. In yeast INO1, it has been shown that Ino80p is recruited to the promoter during repression, and then dissociates from the promoter once de-repression begins. Histone acetylases, on the other hand, have the opposite pattern of recruitment, as they have an increased presence at the promoter as INO1 de-repression commences. This Ino80p recruitment pattern significantly changes when HAT mutant strains are studied. It was observed that instead of dissociating, Ino80p accumulates at the promoter in the absence of functional HATs, such as Gcn5p or Esa1p, under de-repressing processes. As such, Ino80p acetylation may be required for its proper dissociation from the promoters. The remodelers’ dissociation mechanism may also have a wide range of implications with respect to transcriptional initiation, elongation, or even repression as it allows for increased spatial access to the promoter for the various transcription factors and regulators that need to bind in that region. Our findings here suggest a previously uncharacterized interaction between Ino80p and other co-activators recruited to promoters. As such, further analysis of Ino80p acetylation not only will provide insight into the role of epigenetic modifications in transcriptional activation, but also gives insight into the interactions occurring between co-activators at gene promoters during gene regulation.

Keywords: acetylation, chromatin remodeler, epigenetic modification, Ino80p

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Authors: Khaled Alkadamani

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Using the simultaneous equations model, this paper examines the impact of capital requirements on bank risk-taking during the recent financial crisis. It also explores the relationship between capital and risk decisions and the impact of economic instability on this relationship. By analyzing the data of 20 Islamic commercial banks between 2004 and 2014 from four Middle East countries, the study concludes a positive effect of regulatory pressure on bank capital in Saudi Arabia and UAE and a negative effect in Jordan and Kuwait. Moreover, the results show a negative impact of regulatory pressure on bank risk taking in Saudi Arabia, Jordan and UAE. The findings reveal also that banks close to the minimum regulatory capital requirements improve their capital adequacy by increasing their capital and decreasing their risk taking. Furthermore, the results show that economic crisis negatively affects bank risk changes, suggesting that banks react to the impact of uncertainty by reducing their risk taking. Finally, the estimations show a negative correlation between banks profitability and capital adequacy ratio (CAR), implying that as more capital is set aside as a buffer for banks safety; it affects the performance of Islamic banks.

Keywords: bank capital, bank regulation, crisis, Islamic banks, risk taking

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Authors: Agi Sunday, Agih Ukuru Agih

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In Nigeria, the food processing sector is dominated by small and medium enterprises, as well as multinational food companies. Quality standards are usually related to improving the safety of food products suitable for consumption in accordance to specifications by food regulatory bodies. These standards are essential elements for local and international businesses which contribute to economic progress through industrial development and trade. This review takes a critical look on the Nigerian food industry development in terms of quality standards that are necessary to be given consideration in the production of food and also ways of improving food production in Nigeria through the use of Total Quality Management (TQM) technique and the use of computerized systems to produce high quality and high value products while at the same time reducing production time and cost.

Keywords: food industry, quality assurance, Nigeria, TQM, computerized systems

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Authors: Felice Elefant, Akanksha Bhatnaghar, Keegan Krick, Elizabeth Heller

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Context: The severity of Alzheimer’s Disease (AD) progression involves an interplay of genetics, age, and environmental factors orchestrated by histone acetyltransferase (HAT) mediated neuroepigenetic mechanisms. While disruption of Tip60 HAT action in neural gene control is implicated in AD, alternative mechanisms underlying Tip60 function remain unexplored. Altered RNA splicing has recently been highlighted as a widespread hallmark in the AD transcriptome that is implicated in the disease. Research Aim: The aim of this study was to identify a novel RNA binding/splicing function for Tip60 in human hippocampus and impaired in brains from AD fly models and AD patients. Methodology/Analysis: The authors used RNA immunoprecipitation using RNA isolated from 200 pooled wild type Drosophila brains for each of the 3 biological replicates. To identify Tip60’s RNA targets, they performed genome sequencing (DNB-SequencingTM technology, BGI genomics) on 3 replicates for Input RNA and RNA IPs by Tip60. Findings: The authors' transcriptomic analysis of RNA bound to Tip60 by Tip60-RNA immunoprecipitation (RIP) revealed Tip60 RNA targets enriched for critical neuronal processes implicated in AD. Remarkably, 79% of Tip60’s RNA targets overlap with its chromatin gene targets, supporting a model by which Tip60 orchestrates bi-level transcriptional regulation at both the chromatin and RNA level, a function unprecedented for any HAT to date. Since RNA splicing occurs co-transcriptionally and splicing defects are implicated in AD, the authors investigated whether Tip60-RNA targeting modulates splicing decisions and if this function is altered in AD. Replicate multivariate analysis of transcript splicing (rMATS) analysis of RNA-Seq data sets from wild-type and AD fly brains revealed a multitude of mammalian-like AS defects. Strikingly, over half of these altered RNAs were bonafide Tip60-RNA targets enriched for in the AD-gene curated database, with some AS alterations prevented against by increasing Tip60 in fly brain. Importantly, human orthologs of several Tip60-modulated spliced genes in Drosophila are well characterized aberrantly spliced genes in human AD brains, implicating disruption of Tip60’s splicing function in AD pathogenesis. Theoretical Importance: The authors' findings support a novel RNA interaction and splicing regulatory function for Tip60 that may underlie AS impairments that hallmark AD etiology. Data Collection: The authors collected data from RNA immunoprecipitation experiments using RNA isolated from 200 pooled wild type Drosophila brains for each of the 3 biological replicates. They also performed genome sequencing (DNBSequencingTM technology, BGI genomics) on 3 replicates for Input RNA and RNA IPs by Tip60. Questions: The question addressed by this study was whether Tip60 has a novel RNA binding/splicing function in human hippocampus and whether this function is impaired in brains from AD fly models and AD patients. Conclusions: The authors' findings support a novel RNA interaction and splicing regulatory function for Tip60 that may underlie AS impairments that hallmark AD etiology.

Keywords: Alzheimer's disease, cognition, aging, neuroepigenetics

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Authors: Anupama Sahoo, Bongyong Lee, Katia Boniface, Julien Seneschal, Sanjaya K. Sahoo, Tatsuya Seki, Chunyan Wang, Soumen Das, Xianlin Han, Michael Steppie, Sudipta Seal, Alain Taieb, Ranjan J. Perera

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Vitiligo is a common, chronic skin disorder characterized by loss of epidermal melanocytes and progressive depigmentation. Vitiligo has a complex immune, genetic, environmental, and biochemical etiology, but the exact molecular mechanisms of vitiligo development and progression, particularly those related to metabolic control, are poorly understood. Here we characterized the human vitiligo cell line PIG3V and the normal human melanocytes, HEM-l by RNA-sequencing, targeted metabolomics, and shotgun lipidomics. Melanocyte-enriched miR-211, a known metabolic switch in non-pigmented melanoma cells, was severely downregulated in vitiligo cell line PIG3V and skin biopsies from vitiligo patients, while its novel predicted targets transcriptional co-activator PGC1-α (PPARGC1A), ribonucleotide reductase regulatory subunit M2 (RRM2), and serine-threonine protein kinase TAO1 (TAOK1) were reciprocally upregulated. miR-211 binds to PGC1-α 3’UTR locus and represses it. Although mitochondrial numbers were constant, mitochondrial complexes I, II, and IV and respiratory responses were defective in vitiligo cells. Nanoparticle-coated miR-211 partially augmented the oxygen consumption rate in PIG3V cells. The lower oxygen consumption rate, changes in lipid and metabolite profiles, and increased reactive oxygen species production observed in vitiligo cells appear to be partly due to abnormal regulation of miR-211 and its target genes. These genes represent potential biomarkers and therapeutic targets in human vitiligo.

Keywords: metabolism, microRNA, mitochondria, vitiligo

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Authors: Cai Qianyi

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In the midst of global digital revolution, the flow of data poses security threats that call China's existing legislative framework for protecting personal information into question. As a preliminary procedure for risk analysis and prevention, the risk assessment of personal data transmission lacks detailed guidelines for support. Existing provisions reveal unclear responsibilities for network operators and weakened rights for data subjects. Furthermore, the regulatory system's weak operability and a lack of industry self-regulation heighten data transmission hazards. This paper aims to compare the regulatory pathways for data information transmission risks between China and Europe from a legal framework and content perspective. It draws on the “Data Protection Impact Assessment Guidelines” to empower multiple stakeholders, including data processors, controllers, and subjects, while also defining obligations. In conclusion, this paper intends to solve China's digital security shortcomings by developing a more mature regulatory framework and industry self-regulation mechanisms, resulting in a win-win situation for personal data protection and the development of the digital economy.

Keywords: personal information data transmission, risk assessment, DPIA, internet service provider, personal information data transimission, risk assessment

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Authors: Iman Kamranfar, Gang-Ping Xue, Salma Balazadeh, Bernd Mueller-Roeber

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Adverse environmental conditions such as salinity stress, high temperature and drought limit plant growth and typically lead to precocious tissue degeneration and leaf senescence, a process by which nutrients from photosynthetic organs are recycled for the formation of flowers and seeds to secure reaching the next generation under such harmful conditions. In addition, abiotic stress affects developmental patterns that help the plant to withstand unfavourable environmental conditions. We discovered an NAC (for NAM, ATAF1, 2, and CUC2) transcription factor (TF), called RAF in the following, which plays a central role in abiotic drought stress-triggered senescence and the control of developmental adaptations to stressful environments. RAF is an ABA-responsive TF; RAF overexpressors are hypersensitive to abscisic acid (ABA) and exhibit precocious senescence while knock-out mutants show delayed senescence. To explore the RAF gene regulatory network (GRN), we determined its preferred DNA binding sites by binding site selection assay (BSSA) and performed microarray-based expression profiling using inducible RAF overexpression lines and chromatin immunoprecipitation (ChIP)-PCR. Our studies identified several direct target genes, including those encoding for catabolic enzymes acting during stress-induced senescence. Furthermore, we identified various genes controlling drought stress-related developmental changes. Based on our results, we conclude that RAF functions as a central transcriptional regulator that coordinates developmental programs with stress-related inputs from the environment. To explore the potential agricultural applications of our findings, we are currently extending our studies towards crop species.

Keywords: abiotic stress, Arabidopsis, development, transcription factor

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Authors: Kuladip Jana, Bhaswati Banerjee, Parimal C. Sen

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Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems along with carcinogenesis in skin, prostate, ovary, lung and mammary glands. Our study was focused on elucidating the molecular mechanism of B(a)P induced male reproductive toxicity and its prevention with phytochemical like resveratrol. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of Wistar rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased Reactive Oxygen Species (ROS), altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38 mitogen activated protein kinase (p38MAPK), cytosolic translocation of cytochrome-c, upregulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of poly ADP ribose polymerase (PARP) and down regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like steroidogenic acute regulatory protein (StAR), cytochrome P450 IIA1 (CYPIIA1), 3β hydroxy steroid dehydrogenase (3β HSD), 17β hydroxy steroid dehydrogenase (17β HSD) showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis. Next we investigated the role of resveratrol on B(a)P induced male reproductive toxicity. Our study highlighted that resveratrol co-treatment with B(a)P maintained testicular redox potential, increased serum testosterone level and prevented steroidogenic dysfunction with enhanced expression of major testicular steroidogenic proteins (CYPIIA1, StAR, 3β HSD,17β HSD) relative to treatment with B(a)P only. Resveratrol suppressed B(a)P-induced testicular activation of p38 MAPK, ATF2, iNOS and ROS production; cytosolic translocation of Cytochome c and Caspase 3 activation thereby prevented oxidative stress of testis and inhibited apoptosis. Resveratrol co-treatment also decreased B(a)P-induced AhR protein level, its nuclear translocation and subsequent CYP1A1 promoter activation, thereby decreased protein and mRNA levels of testicular cytochrome P4501A1 (CYP1A1) and prevented BPDE-DNA adduct formation. Our findings cumulatively suggest that resveratrol prevents activation of B(a)P by modulating the transcriptional regulation of CYP1A1 and acting as an antioxidant thus prevents B(a)P-induced oxidative stress and testicular apoptosis.

Keywords: benzo(a)pyrene, resveratrol, testis, apoptosis, cytochrome P450 1A1 (CYP1A1), aryl hydrocarbon receptor (AhR), p38 MAPK/ATF2/iNOS

Procedia PDF Downloads 197