Search results for: transcriptional regulation

Authors: Jakob Krause

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Past Financial Crisis has shown that contemporary risk management models provide an unjustified sense of security and fail miserably in situations in which they are needed the most. In this paper, we start from the assumption that risk is a notion that changes over time and therefore past data points only have limited explanatory power for the current situation. Our objective is to derive the optimal amount of representative information by optimizing between the two adverse forces of estimator convergence, incentivizing us to use as much data as possible, and the aforementioned non-representativeness doing the opposite. In this endeavor, the cornerstone assumption of having access to identically distributed random variables is weakened and substituted by the assumption that the law of the data generating process changes over time. Hence, in this paper, we give a quantitative theory on how to perform statistical analysis in non-ergodic systems. As an application, we discuss the impact of a paragraph in the last iteration of proposals by the Basel Committee on Banking Regulation. We start from the premise that the severity of assumptions should correspond to the robustness of the system they describe. Hence, in the formal description of physical systems, the level of assumptions can be much higher. It follows that every concept that is carried over from the natural sciences to economics must be checked for its plausibility in the new surroundings. Most of the probability theory has been developed for the analysis of physical systems and is based on the independent and identically distributed (i.i.d.) assumption. In Economics both parts of the i.i.d. assumption are inappropriate. However, only dependence has, so far, been weakened to a sufficient degree. In this paper, an appropriate class of non-stationary processes is used, and their law is tied to a formal object measuring representativeness. Subsequently, that data set is identified that on average minimizes the estimation error stemming from both, insufficient and non-representative, data. Applications are far reaching in a variety of fields. In the paper itself, we apply the results in order to analyze a paragraph in the Basel 3 framework on banking regulation with severe implications on financial stability. Beyond the realm of finance, other potential applications include the reproducibility crisis in the social sciences (but not in the natural sciences) and modeling limited understanding and learning behavior in economics.

Keywords: banking regulation, non-ergodicity, risk management, semimartingale modeling

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Authors: Pumela Msweli, Dexter L. Ryneveldt

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This paper seeks to shed light on institutional logics and institutionalization processes that influence the successful implementation of financial sector regulations. We use the neo-institutional theory lens to interrogate how the newly promulgated Financial Sector Regulations Act (FSRA) provides for the institutionalisation of the Twin Peaks Model. With the enactment of FSRA, previous financial regulatory institutions were dismantled, and new financial regulators established. In point, the Financial Services Conduct Authority (FSCA) replaced the Financial Services Board (FSB), and accordingly, the Prudential Authority (PA) was established. FSRA is layered with complexities that make it mandatory to co-exist, cooperate, and collaborate with other institutions to fulfill FSRA’s overall financial stability objective. We use content analysis of the financial regulations that established the Twin Peaks Models (TPM) in South Africa and in the Netherlands, to map out the three-stage institutionalization processes: (1) habitualisation, (2) objectification and (3) sedimentation. This allowed for a comparison of how South Africa, as a developing country and Netherlands as a developed country, have institutionalized the Twin Peak model. We provide valuable insights into how differences in the institutional and societal logics of the developing and developed contexts shape the institutionalization of financial regulations.

Keywords: financial industry, financial regulation, financial stability, institutionalisation, habitualization, objectification, sedimentation, twin peaks model

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Authors: Bruno de Almeida Vilela, Heinz Ahn, Ana Lúcia Miranda Lopes, Marcelo Azevedo Costa

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Benchmarking public utilities such as transmission system operators (TSOs) is one of the main strategies employed by regulators in order to fix monopolistic companies’ revenues. Since 2007 the Brazilian regulator has been utilizing Data Envelopment Analysis (DEA) to benchmark TSOs. Despite the application of DEA to improve the transmission sector’s efficiency, some problems can be pointed out, such as the high price of electricity in Brazil; the limitation of the benchmarking only to operational expenses (OPEX); the absence of variables that represent the outcomes of the transmission service; and the presence of extremely low and high efficiencies. As an alternative to the current concept of benchmarking the Brazilian regulator uses, we propose a goal-oriented approach. Our proposal supports input/output selection by taking traditional organizational goals and measures as a basis for the selection of factors for benchmarking purposes. As the main advantage, it resolves the classical DEA problems of input/output selection, undesirable and dual-role factors. We also provide a demonstration of our goal-oriented concept regarding service quality. As a result, most TSOs’ efficiencies in Brazil might improve when considering quality as important in their efficiency estimation.

Keywords: decision making, goal-oriented benchmarking, input/output factor determination, TSO regulation

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Authors: Suman Podder

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As Australian ‘Open Banking’ allows customers to share their financial data with accredited Third-Party Providers (‘TPPs’), it is necessary to evaluate whether the regulators have achieved the balance between protecting customer data privacy and promoting data-related innovation. Recognising the need to increase customers’ influence on their own data, and the benefits of data-related innovation, the Australian Government introduced ‘Consumer Data Right’ (‘CDR’) to the banking sector through Open Banking regulation. Under Open Banking, TPPs can access customers’ banking data that allows the TPPs to tailor their products and services to meet customer needs at a more competitive price. This facilitated access and use of customer data will promote innovation by providing opportunities for new products and business models to emerge and grow. However, the success of Open Banking depends on the willingness of the customers to share their data, so the regulators have augmented the protection of data by introducing new privacy safeguards to instill confidence and trust in the system. The dilemma in policymaking is that, on the one hand, lenient data privacy laws will help the flow of information, but at the risk of individuals’ loss of privacy, on the other hand, stringent laws that adequately protect privacy may dissuade innovation. Using theoretical and doctrinal methods, this paper examines whether the privacy safeguards under Open Banking will add to the compliance burden of the participating financial institutions, resulting in the undesirable effect of stifling other policy objectives such as innovation. The contribution of this research is three-fold. In the emerging field of customer data sharing, this research is one of the few academic studies on the objectives and impact of Open Banking in the Australian context. Additionally, Open Banking is still in the early stages of implementation, so this research traces the evolution of Open Banking through policy debates regarding the desirability of customer data-sharing. Finally, the research focuses not only on the customers’ data privacy and juxtaposes it with another important objective of promoting innovation, but it also highlights the critical issues facing the data-sharing regime. This paper argues that while it is challenging to develop a regulatory framework for protecting data privacy without impeding innovation and jeopardising yet unknown opportunities, data privacy and innovation promote different aspects of customer welfare. This paper concludes that if a regulation is appropriately designed and implemented, the benefits of data-sharing will outweigh the cost of compliance with the CDR.

Keywords: consumer data right, innovation, open banking, privacy safeguards

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Authors: Siavash Ostovar

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The Iranian national Law on the Ramsar Convention (officially known as the Convention of International Wetlands and Aquatic Birds' Habitat Wetlands) was approved by the Senate and became a law in 1974 after the ratification of the National Council. There are other national laws with the aim of preservation of environment in the country. However, Lake Urmia which is declared a wetland of international importance by the Ramsar Convention in 1971 and designated a UNESCO Biosphere Reserve in 1976 is now at the brink of total disappearance due mainly to the climate change, water mismanagement, dam construction, and agricultural deficiencies. Lake Urmia is located in the north western corner of Iran. It is the third largest salt water lake in the world and the largest lake in the Middle East. Locally, it is designated as a National Park. It is, indeed, a unique lake both nationally and internationally. This study investigated how effective the national legal regulation of the ecosystem of Lake Urmia is in Iran. To do so, the Iranian national laws as Enforcement of Ramsar Convention in the country including three nationally established laws of (i) Five sets of laws for the programme of economic, social and cultural development of Islamic Republic of Iran, (ii) The Iranian Penal Code, (iii) law of conservation, restoration and management of the country were investigated. Using black letter law methods, it was revealed that (i) regarding the national five sets of laws; the benchmark to force the implementation of the legislations and policies is not set clearly. In other words, there is no clear guarantee to enforce these legislations and policies at the time of deviation and violation; (ii) regarding the Penal Code, there is lack of determining the environmental crimes, determining appropriate penalties for the environmental crimes, implementing those penalties appropriately, monitoring and training programmes precisely; (iii) regarding the law of conservation, restoration and management, implementation of this regulation is adjourned to preparation, announcement and approval of several categories of enactments and guidelines. In fact, this study used a national environmental catastrophe caused by drying up of Lake Urmia as an excuse to direct the attention to the weaknesses of the existing national rules and regulations. Finally, as we all depend on the natural world for our survival, this study recommended further research on every environmental issue including the Lake Urmia.

Keywords: conservation, environmental law, Lake Urmia, national laws, Ramsar Convention, water management, wetlands

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Authors: Alan S. Weber

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This contribution reviews the current biomedical and qualitative arts research on arts-in-health interventions to improve both individual and population health outcomes. Arts therapies–for example, music therapy with roots in Aristoxenus’s Ἁρμονικὰ στοιχεῖα and the Pythagorean sect–have long been employed in therapeutic contexts. However, the 20th century witnessed the increasing use of the visual and plastic arts (drawing, painting, sculpting), performing arts (drama and dance), and other expressive arts modalities into occupational therapy, well-being medicine, and psychological and psychiatric counselling, diagnosis, and treatment. A significant body of peer-reviewed evidence in the medical and neurological sciences on the role of arts-in-health has developed, and specifically, research on music and art therapy has led to their inclusion within the current biomedical paradigm of evidence-based practice. The arts cannot only aid in public and population health promotion (promoting healthy behaviors and lifestyles, preventing disease onset) but also in addressing psychological issues (regulation of emotion; stress, anxiety, and depression reduction), behavioural issues (basic life skills, coping), and physiological response (immune system function, hormonal regulation, homeostatis). Working as a cross-disciplinary researcher in the arts in an American medical college, the author has developed several successful arts-in-health programs at the national and international level.

Keywords: arts-in-health, evidence based medicine, arts for health, expressive arts therapies

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Authors: Neda Menbari, Ramin Mehdiabadi

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Background: breast cancer remains a critical global health issue, constituting a leading cause of cancer-related mortality in women. MicroRNAs (miRs) are natural RNA molecules that play an important role in cellular processes and regulate post-transcriptional gene expression. MiR-216b-5p is a miR that acts as a tumor suppressor. The expression levels of FoxM1 and miR-216b-5p in malignant and control cells have been evaluated by quantitative polymerase chain reaction (qPCR) technique and flow cytometry. Results: the results of this study revealed a significant downregulation of miR-216b-5p in cancerous cells compared to the control MCF-10A cells (P=0.0004). Interestingly, the expression of miR-216b-5p exhibited an inverse relationship with key clinical indicators such as tumor size, grade, and lymph node invasion. Conclusion: The study's findings showed the prognostic value of miR-216b-5p levels in breast cancer, and its reduced expression correlates with unfavorable tumor characteristics. This research recommends performing more studies on the role of FoxM1 and miR-216b-5p in breast cancer pathology which potentially paving the way for targeted therapeutic interventions.

Keywords: breast cancer, gene expression, FOXM1, microRNA

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Authors: Aslanova Aida Ramiz

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One of the important aspects of rheophysical problems in oil and gas extraction is the regulation of thermohydrodynamic properties of liquid systems using physical and physicochemical methods. It is known that the constituent parts of real fluid systems in oil and gas production are practically non-conducting, non-magnetically active components. Real heterogeneous hydrocarbon systems, from the structural point of view, consist of an infinite number of microscopic local ion-electrostatic cores distributed in the volume of the dispersion medium. According to Cohen's rule, double electric layers are formed at the contact boundaries of components in contact (oil-gas, oil-water, water-condensate, etc.) in a heterogeneous system, and as a result, each real fluid system can be represented as a complex composition of a set of local electrostatic fields. The electrokinetic properties of this structure are characterized by a certain electrode potential. Prof. F.H. Valiyev called this potential the α-factor and came up with the idea that many natural and technological rheophysical processes (effects) are essentially electrokinetic in nature, and by changing the α-factor, it is possible to adjust the physical properties of real hydraulic systems, including thermohydrodynamic parameters. Based on this idea, extensive research work was conducted, and the possibility of reducing hydraulic resistances and improving rheological properties was experimentally discovered in real liquid systems by reducing the electrical potential with various physical and chemical methods.

Keywords: microcracked, electrode potential, hydraulic resistance, Newtonian fluid, rheophysical properties

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Authors: Anjani Kumar Tiwari, Neelam Kumari, Anil Mishra

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The family of phosphodiesterases (PDEs) plays a critical role in control of the level, localization, and duration of intracellular 3’-5’-cyclic adenosine monophosphate (cAMP) and 3’-5’-cyclic guanosine monophosphate (cGMP) signals by specifically hydrolyzing these cyclic nucleotides. As the involvement of cyclic nucleotide second messengers in cell signaling and homeostasis is established, the regulation of these pathways in the brain by various PDE isoforms is an area of considerable interest, as they are involved in nearly all brain functions and in the etiology of neuropsychiatric diseases. The PDE10A isoform, isolated from different species and characterized regarding structure and function, has received much attention in recent years, particularly in the context of schizophrenia and Huntington’s disease, which are both related to a role of PDE10A in the regulation of striatal dopaminergic neurotransmission. Quinazoline analogue 1-(4-methoxyphenyl)-6,7-dimethoxyquinazoline, was evaluated as specific PET marker for phosphodiesterase (PDE) 10A. Here, we report the radiosynthesis of [11C]2 and the in vitro and in vivo evaluation of [11C]2 as a potential positron emission tomography (PET) radiotracer for imaging PDE10A in the central nervous system (CNS). The radiosynthesis of [11C]2 was achieved by O-methylation of the corresponding des-methyl precursor with [11C]methyl iodide. [11C]2 was obtained with ∼50% radiochemical yield. PET imaging studies in rat brain displayed initial specific uptake with very rapid clearance of [11C]2 from brain. Though [11C]2 is not an ideal radioligand for clinical imaging of PDE10A in the CNS. Modified analogue of quinazoline having a higher potency for inhibiting PDE10A and improved pharmacokinetic properties will be necessary for imaging this enzyme with PET.

Keywords: PDE10A, PET, radiotracer, quinazoline

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Authors: Tamas Bezsenyi, Noemi Katona

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Fighting Human Trafficking is a highly important issue worldwide that states need to deal with in international politics. In the EU combatting human trafficking is emphasized in international policy making and also in the work of international law enforcement, thus in the work of the EUROPOL. While the EU Directive against Human Trafficking prescribes how states should fight this transnational crime and also how victims should be assisted, the EUROPOL focuses on the effective cooperation between national law enforcement agencies. However, despite the aims of the common fight, human trafficking is regulated differently in the punitive law of various nation states. This deeply defines the work and possibilities of national law enforcement organizations. Among the manifold differences in this paper, we focus on the role of regulating asset recovery. We highlight that money, and the regulation and practice how the law enforcement deals with income gained from criminal activities, play essential role in combatting human trafficking. While doing research on the investigation of transnational human trafficking by the Hungarian Law Enforcement Agencies, we have found that the unfortunate regulation of asset recovery determines the lower effectiveness of eliminating criminal organizations. While i.e. in the Netherlands confiscation of property takes place in an early stage of the criminal procedure, in Hungary it can be conducted only if money laundering is also assumed. Our presentation builds on the comparison of criminal procedures which we analyse based on criminal files and interviews with coworkers of the National Bureau of Investigation.

Keywords: human trafficking, law enforcement, asset recovery, organized crime

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Authors: Liya Abraham

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Eritrea is located along the Red Sea, north of the Horn of Africa, between Djibouti and Sudan and has a population of about 3.2 million as of 2010. It has six administrative regions; Anseba, Debub, Debubawi K’eyih Bahri, Gash-Barka, Ma'akel, and Semenawi K’eyih Bahri. Eritrea has got its independence in 1991 after 30 years war of liberation. The country is blessed with various medicinal flora and fauna, and marine and terrestrial biodiversity. Traditional Medicine (TM) has been an integral part of the Eritrean culture for centuries. So far, more than 19 TM modalities have been recognized, and are broadly categorized as; herbal, procedure-based and spiritual. Despite the availability of modern medicine to the majority of the population, TM is still widely practiced. The rationale behind widespread use is accessibility, affordability and cultural acceptability. Hence, TM is of great contribution to the Eritrean health care system. As a matter of fact, harnessing the potential contribution of effective and safe TM in order to attain Universal Health Coverage (UHC) has been emphasized in the WHO TM strategy 2014-2023. The Eritrean TM, however, was operating without regulation and reliable scientific justification behind its safety and efficacy. Thus, the Ministry of Health (MoH), in recognition of the role of TM in primary healthcare and safeguard public health, established a regulatory body for TM so-called as Traditional Medicine Unit (TMU) in 2012. The mission of the unit is to ensure rational TM use through an integrated health service delivery system and contribute to the country’s economic and social development. The unit has established its national TM policy in 2017. The activities of the unit are guided by the National TM Advisory Committee (TMAC), responsible for the provision of technical assistance and advisory role. Moreover, the Legal Framework and Code of Ethics and Practice which provide a legal basis for the regulation of TM have also been drafted. In recognition of the importance of TM research and development, the unit launched a nationwide TM survey in 2017 and had surveyed two zones (Gash-Barka and Debub). The findings of the survey were subjected to a research dissemination workshop and publication in international journals. Furthermore, TM-related adverse events reporting tool (Green Form) aiming to guide regulatory interventions and researches have been established by the unit, and ever since reports are flowing. The unit has also been offering training to THPs, pharmacy students and health care professionals regarding TM and its regulatory activities. In addition, as part of the establishment of the national medicinal plants' database and herbal monograph, more than 329 and 30 medicinal plants, have been compiled respectively. In conclusion, TM is still widely accepted and practiced in Eritrea. The TMU ever since its establishment is endeavoring to ensure the safety and efficacy of the TM, and its integration in the mainstream health service delivery system.

Keywords: efficacy, regulation, safety, traditional medicine, traditional medicine unit, universal health coverage

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Authors: Ana Tsokilauri

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The uppermost factor in the regulation of lignin-cellulose activity of decaying white rot or free rot are the substances serving as carbon and nitrogen nutrition of microorganisms and are considered as the most important factor of generative activity of white rot. The research object was Basidiomycete Fungi, peculiar and common in Georgia, and the separation of 10 of them as pure crops. The unidentified pure crops have tasted in order to be determined the potential of synthesis of lignin-degrading enzymes and the substrate of optimal lignocellulose growth. One of the most important aspects of the research conducted on Basidiomycetes was the use of specific lignocellulosic residues for selecting Fungi as a substrate of their growth. In order to increase lignocellulose with the help of substrate, crops were selected from the screening stage that showed good laccase activity. (Dusheti 1; Dusheti 10; Fshavi 5; Fshavi1; Fshavi 8; Fshavi 32; Manglisi 26; Sabaduri20; Dusheti 7; Sabaduri 1 ), Among the selected cultures, the crops with good laccase activity against the following substances, in particular: Dusheti 1- in this case, the rate of enzymatic activity on bran substrate was -105,6 u/ml, mandarin-96,4 u/ml. In case of corn - 102,9 u/ml. In case of Dusheti 7- the indicators were as follows: bananas-121,7 u/ml, mandarin-125,4 u/ml, corn - 117,1 u/ml. In the case of Sanaduri 32, the laccase activity was as follows: pomegranate- 101,2 u/ml. As a result of conducted experiments, the synthesis and activity rates of enzymes depending on plant substrates varied within a fairly wide range, which is still being under research.

Keywords: Lignocellulosic substrate, Basidiomycetes, white-rot basidiomycetes, Laccase

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Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang

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Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.

Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation

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Authors: Chin Ku, Han liang Lin

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The purpose of this study is to visualize how the rule related to urban design influences the building form by 3D modeling software CityEngine. In order to make the goal of urban design clearly connect to urban form, urban planner or designer should understand how the rule affects the form, especially the building form. In Taiwan, the rule pertained to urban design includes traditional zoning, urban design review and building codes. However, zoning cannot precisely expect the outcome of building form and lack of thinking about public realm and 3D form. In addition to that, urban design review is based on case by case, do not have a comprehensive regulation plan and the building code is just for general regulation. Therefore, rule cannot make the urban form reach the vision or goal of the urban design. Consequently, another kind of zoning called Form-based code (FBC) has arisen. This study uses the component of FBC which pertained to urban fabric such as street width, block and plot size, etc., to be the variants of building form, and find out the relationship between the rule and building form. There are three stages of this research, it will start from a field survey of Taichung City in Taiwan to induce the rule-building form relationship by using cluster analysis and descriptive Statistics. Second, visualize the relationship through the parameterized and codified process in CityEngine which is the procedural modeling, and can analyze, monitor and visualize the 3D world. Last, compare the CityEngine result with real world to examine how extent do this model represent the real world appearance.

Keywords: 3D visualization, CityEngine, form-based code, urban form

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Authors: Arash Sepehri bonab

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One of the regions of critical development in medical devices has been the part of the software - as an indispensable component of a therapeutic device, as a standalone device, and more as of late, as applications on portable gadgets. The chance related to a breakdown of the standalone computer program utilized inside healthcare is in itself not a model for its capability or not as a medical device. It is, subsequently, fundamental to clarify a few criteria for the capability of a stand-alone computer program as a medical device. The number of computer program items and therapeutic apps is persistently expanding and so as well is used in wellbeing education (e. g., in clinics and doctors' surgeries) for determination and treatment. Within the last decade, the use of information innovation in healthcare has taken a developing part. In reality, the appropriation of an expanding number of computer devices has driven several benefits related to the method of quiet care and permitted simpler get to social and health care assets. At the same time, this drift gave rise to modern challenges related to the usage of these modern innovations. The program utilized in healthcare can be classified as therapeutic gadgets depending on the way they are utilized and on their useful characteristics. In the event that they are classified as therapeutic gadgets, they must fulfill particular directions. The point of this work is to show a computer program improvement system that can permit the generation of secure and tall, quality restorative gadget computer programs and to highlight the correspondence between each program advancement stage and the fitting standard and/or regulation.

Keywords: medical devices, regulation, software, development, healthcare

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Authors: Siqing Guan, Fumiyo Oshima, Eiji Shimizu, Nozomi Tomita, Toru Takahashi, Hiroaki Kumano

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Risk factors for social anxiety in autism spectrum conditions involve executive attention, emotion regulation, and thought regulation as processes of cognitive dysregulation. Social camouflaging behaviors as strategies used to mask and/or compensate for autism characteristics during social interactions in autism spectrum conditions have also been emphasized. However, the role of cognitive dysregulation and social camouflaging related to social anxiety in autism spectrum conditions has not been clarified. Whether these factors are specific to social anxiety in autism spectrum conditions or common to social anxiety independent of autism spectrum conditions needs to be clarified. Here, we explored risk factors specific to social anxiety in autism spectrum conditions and general risk factors for social anxiety independent of autism spectrum conditions. From the Japanese participants in early adulthood (age=18~39) of the online survey in Japan, those who exceeded the Japanese version Autism-Spectrum Quotient cutoff (33 points or more )were divided into the autism spectrum conditions group (ASC; N=255, mean age=32.08, SD age=5.16)and those who did not exceed the cutoff were divided into the non-autism spectrum conditions group (Non-ASC; N=255, mean age=31.70, SD age=5.09). Using the Japanese versions of the Social Phobia Scale, the Social Interaction Anxiety Scale, and the Short Fear of Negative Evaluation Scale, a composite score for social anxiety was calculated using a method of principal. We also measured emotional control difficulties using the Difficulties in Emotion Regulation Scale, executive attention using the Effortful Control Scale for Adults, rumination using the Rumination-Reflection Questionnaire, and worry using the Penn State Worry Questionnaire. This study was passed through the review of the Ethics Committee. No conflicts of interest. Multiple regression analysis with forced entry method was used to predict social anxiety in the ASC and non-ASC groups separately, based on executive attention, emotion dysregulation, worry, rumination, and social camouflage. In the ASC group, emotion dysregulation (β=.277, p<.001), worry (β=.162, p<.05), assimilation (β=.308, p<.001) and masking (β=.275, p<.001) were significant predictors of social anxiety (F (7,247) = 45.791, p <.001, R2=.565). In the non-ASC groups,emotion dysregulation (β=.171, p<.05), worry (β=.344，p <.001), assimilation (β=.366,p <.001) and executive attention (β=-.132,p <.05) were significant predictors of social anxiety (F (7,207) =47.333, p <.001, R2=.615).The findings suggest that masking was shown to be a risk factor for social anxiety specific to autism spectrum conditions, while emotion dysregulation, worry, and assimilation were shown to be common risk factors for social anxiety, regardless of autism spectrum conditions. In addition, executive attention is a risk factor for social anxiety without autism spectrum conditions.

Keywords: autism spectrum, cognitive control, social anxiety, social camouflaging

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Authors: Lu Yang, Keng Po Lai

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Metformin, a well-known clinical drug against diabetes, is found with potential anti-diabetic and anti-obese benefits, as reported in increasing evidences. However, the current clinical and experimental investigations are not to reveal the detailed mechanisms of metformin-anti-obesity/hypertension. We have used the bioinformatics strategy, including network pharmacology and molecular docking methodology, to uncover the key targets and pathways of bioactive compounds against clinical disorders, such as cancers, coronavirus disease. Thus, in this report, the in-silico approach was utilized to identify the hug targets, pharmacological function, and mechanism of metformin against obesity and hypertension. The networking analysis identified 154 differentially expressed genes of obesity and hypertension, 21 interaction genes, and 6 hug genes of metformin treating hypertensive obesity. As a result, the molecular docking findings indicated the potent binding capability of metformin with the key proteins, including interleukin 6 (IL-6) and chemokine (C-C motif) Ligand 2 (CCL2), in hypertensive obesity. The metformin-exerted anti-hypertensive obesity action involved in metabolic regulation, inflammatory reaction. And the anti-hypertensive obesity mechanisms of metformin were revealed, including regulation of inflammatory and immunological signaling pathways for metabolic homeostasis in tissue and microenvironmental melioration in blood pressure. In conclusion, our identified findings with bioinformatics analysis have demonstrated the detailed hug and pharmacological targets, biological functions, and signaling pathways of metformin treating hypertensive obesity.

Keywords: metformin, obesity, hypertension, bioinformatics findings

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Authors: Marin Mandić, Elis Sutlović, Tonći Modrić, Luka Stanić

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With the restructuring and deregulation of the power system, storage owners, generation companies or private producers can offer their multiple services on various power markets and earn income in different types of markets, such as the day-ahead, real-time, ancillary services market, etc. During the COVID-19 pandemic, electricity prices, as well as ancillary services prices, increased significantly. The optimization of the energy storage operation was performed using a suitable model for simulating the operation of a pumped storage hydropower plant under market conditions. The objective function maximizes the income earned through energy arbitration, regulation-up, regulation-down and spinning reserve services. The optimization technique used for solving the objective function is mixed integer linear programming (MILP). In numerical examples, the pumped storage hydropower plant operation has been optimized considering the already achieved hourly electricity market prices from Nord Pool for the pre-pandemic (2019) and the pandemic (2020 and 2021) years. The impact of the electricity market prices during the COVID-19 pandemic on energy storage operation is shown through the analysis of income, operating hours, reserved capacity and consumed energy for each service. The results indicate the role of energy storage during a significant fluctuation in electricity and services prices.

Keywords: electrical market prices, electricity market, energy storage optimization, mixed integer linear programming (MILP) optimization

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Authors: Sheng-Hui Lan, Shan-Ying Wu, Shu-Ching Lin, Wei-Chen Wang, Hsiao-Sheng Liu

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Autophagy is an essential mechanism to maintain cellular homeostasis through its degradation function, and the autophagy deficiency is related various diseases including tumorigenesis in several cancers. MicroRNAs (miRNAs) are small none coding RNAs, which regulate gene expression through degradation of mRNA or inhibition of translation. However, the relationship between autophagy deficiency and dysregulated miRNAs is still unclear. We revealed a mechanism that autophagy up-regulates miR-449a expression at the transcriptional level through activation of forkhead transcription factor family member FoxO1 and then suppresses tumorigenesis in CRC. Our data showed that the autophagic activity and miR-449a expression were lower in colorectal cancer (CRC) and has a positive correlation. We further reveal that autophagy degrades p300 expression and then suppresses acetylation of FoxO1. Under autophagic induction conditions, FoxO1 is transported from the cytoplasm to the nucleus and binds to the miR-449a promoter and then promotes miR-449a expression. In addition, either miR-449a overexpression or amiodarone-induced autophagy inhibits cell cycle progression, proliferation, colony formation migration, invasion, and tumor formation of SW480 cells. Our findings indicate that autophagy inducers may have the potential to be used for prevention and treatment of CRC through upregulation of miR-449a expression.

Keywords: autophagy, MiR-449a, FoxO1, colorectal cancer

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Authors: Emanuela Chiarella, Annamaria Aloisio, Nisticò Clelia, Maria Mesuraca

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ZNF521 is a stem cell-associated transcription co-factor, that plays a crucial role in the homeostatic regulation of the stem cell compartment in the hematopoietic, osteo-adipogenic, and neural system. In normal hematopoiesis, primary human CD34+ hematopoietic stem cells display typically a high expression of ZNF521, while its mRNA levels rapidly decrease when these progenitors progress towards erythroid, granulocytic, or B-lymphoid differentiation. However, most acute myeloid leukemias (AMLs) and leukemia-initiating cells keep high ZNF521 expression. In particular, AMLs are often characterized by chromosomal translocations involving the Mixed Lineage Leukemia (MLL) gene, which MLL gene includes a variety of fusion oncogenes arisen from genes normally required during hematopoietic development; once they are fused, they promote epigenetic and transcription factor dysregulation. The chromosomal translocation t(9;11)(p21-22;q23), fusing the MLL gene with AF9 gene, results in a monocytic immune phenotype with an aggressive course, frequent relapses, and a short survival time. To better understand the dysfunctional transcriptional networks related to genetic aberrations, AML gene expression profile datasets were queried for ZNF521 expression and its correlations with specific gene rearrangements and mutations. The results showed that ZNF521 mRNA levels are associated with specific genetic aberrations: the highest expression levels were observed in AMLs involving t(11q23) MLL rearrangements in two distinct datasets (MILE and den Boer); elevated ZNF521 mRNA expression levels were also revealed in AMLs with t(7;12) or with internal rearrangements of chromosome 16. On the contrary, relatively low ZNF521 expression levels seemed to be associated with the t(8;21) translocation, that in turn is correlated with the AML1-ETO fusion gene or the t(15;17) translocation and in AMLs with FLT3-ITD, NPM1, or CEBPα double mutations. Invitro, we found that the enforced co-expression of ZNF521 in cord blood-derived CD34+ cells induced a significant proliferative advantage, improving MLL-AF9 effects on the induction of proliferation and the expansion of leukemic progenitor cells. Transcriptome profiling of CD34+ cells transduced with either MLL-AF9, ZNF521, or a combination of the two transgenes highlighted specific sets of up- or down-regulated genes that are involved in the leukemic phenotype, including those encoding transcription factors, epigenetic modulators, and cell cycle regulators as well as those engaged in the transport or uptake of nutrients. These data enhance the functional cooperation between ZNF521 and MA9, resulting in the development, maintenance, and clonal expansion of leukemic cells. Finally, silencing of ZNF521 in MLL-AF9-transformed primary CD34+ cells inhibited their proliferation and led to their extinction, as well as ZNF521 silencing in the MLL-AF9+ THP-1 cell line resulted in an impairment of their growth and clonogenicity. Taken together, our data highlight ZNF521 role in the control of self-renewal and in the immature compartment of malignant hematopoiesis, which, by altering the gene expression landscape, contributes to the development and/or maintenance of AML acting in concert with the MLL-AF9 fusion oncogene.

Keywords: AML, human zinc finger protein 521 (hZNF521), mixed lineage leukemia gene (MLL) AF9 (MLLT3 or LTG9), cord blood-derived hematopoietic stem cells (CB-CD34+)

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Authors: Renu Yadav, Sanjeev Kumar

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In northern India, chickpea (Cicer arietinum L.) come across with terminal high-temperature stress during reproductive stage which leads to reduced yield. Hence, stable production of chickpea will depend on the development of new methods like ‘priming’ which allow improved adaptation to the drought and heat stress. In the present experiment, 11-day chickpea seedling was primed with mild drought stress and put on recovery stage by irrigating and finally 30-day seedlings were exposed to heat stress 38°C (4 hours), 35°C (8 hours) and 32°C (12 hours). To study the effect of combinatorial stress, heat and drought stress was applied simultaneously. Analyses of various physiological parameters like membrane damage assay, photosynthetic pigments, antioxidative enzyme, total sugars were estimated at all stages. To study the effect of heat stress on the metabolites of the plants, GC-MS and HPLC were performed, while at transcriptional level Real-Time PCR of predicted heat stress-related genes was done. It was concluded that the heat stress significantly affected the chickpea plant at physiological and molecular level in all the five varieties. Results also show less damaging effect in primed plants by increasing the activity of antioxidative enzymes and increased expression of heat shock proteins and heat shock factors.

Keywords: chickpea, combinatorial stress, heat stress, oxidative stress, priming, RT-PCR

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Authors: Jie Ding, Yingying Pan, Shammy Raj, Lindy Schaffrick, Jolene Wong, Antoinette Nguyen, Sharada Manchikanti, Larry Unsworth, Peter Kwan, Edward E. Tredget

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Background: Exosomes (EXOs) have been considered a new target that is thought to be involved in and treat wound healing. More research is needed to fully understand the EXO characteristics and mechanisms of EXO-mediated wound healing, especially wound healing after burn injury. Methods: Total EXOs were isolated from 85 serum samples of 29 burn patients and 13 healthy individuals. We characterized the EXOs for morphology and density, serum concentration, protein level, marker expression, size distribution, and cytokine content. After confirmation of EXO uptake by dermal fibroblasts, we also explored functional regulation of primary human normal skin and hypertrophic scar fibroblast cell lines by the EXOs in vitro, including cell proliferation and apoptosis. Results: EXOs dynamically changed their morphology, density, size, and cytokine level during wound healing in burn patients, which were correlated with burn severity and the stages of wound healing. EXOs from both burn patients and healthy individuals stimulated dermal fibroblast proliferation and apoptosis. Conclusion: EXO features may be important signals that influence wound healing after burn injury; however, to understand the mechanisms by which EXOs regulated the fibroblasts in healing wounds, further studies will be required in the future.

Keywords: exosome, burn, wound healing, hypertrophic scarring, cytokines

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Authors: Shuchi Bharti

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This article intends to analyse the transforming nature of state and corporate sector relationship in the light of evolving regulatory and institutional aspects pertaining to Corporate Social Responsibility (CSR) in India. The focus is on evaluating the accounts of law and decentred discourses, relevant within the changing regulatory and institutional paradigm that substantially goes ahead of formal legal control of state towards corporate actors. At this vantage point, it is important to understand the state’s posture towards a changing scenario particularly as the tone is set by regulatory parameters pertaining to CSR to drive process of engagement with the stakeholders. The tripartite framework of the article intends to focus on finding on the vital interconnected aspects of the CSR provisions (Section 135) of The Companies Act 2013 (The Act), rise of new institutions and the emergence of the decentred regulatory space. Thus is earmarked in a neo-liberal paradigm; state is witnessed to perform a responsive function in engendering enhanced public role for the corporate sector. In this overarching framework the aim is to undertake a causal, exploratory and relational analysis of aspects pertaining law, regulation and institutional transformations. Firstly, focus is drawn on to investigate the relational facets of the advent of law and regulatory framework of CSR. Secondly, in the light of the historical evolution, a causal connection is attempted between globalization, emergence of international soft law framework and the Indian case of CSR. Finally, I look into how the new Companies Act mandates CSR expenditure vis- a -vis multiple parameters and guidelines.

Keywords: corporate social responsibility, stakeholders, soft law, decentred regulation

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Authors: Hayyan ul Haq, Zainal Asikin

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This work aims to explore the appropriate solution in solving legal problems stemmed from managing and exploiting strategic natural resources in Indonesia. This discussion will be focused on the exploitation of gold mining, i.e. divestation process in the New Mont Corporation, West Nusa Tenggara. These legal problems relate to the deviation of the national budget regulation, UU. No. 19/2012, and the implementation of the divestastion process, which infringes PP. No. 50/2007 concerning the Impelementation Procedure of Regional Cooperation, which is an implementation regulation of UU No. 1/2004 on State’s Treasury. The cooperation model, have been developed by the Provincial Government, failed to create a permanent legal solution through normative approach. It has merely used practical approach that tends (instant solution), by using some loopholes in the divestation process. The above blunders have accumulated by other secondary legal blunders, i.e. good governance principles, particularly justice, transparency, efficiency, effective principles and competitiveness principle. To solve the above problems, this work offers constitutionalisation of contract that aimed at reviewing and coherencing all deviated contracts, rules and policies that have deprived the national and societies’ interest to optimize the strategic natural resources towards the greatest benefit for the greatest number of people..

Keywords: constitutionalisation of contract, strategic national resources, divestation, the greatest benefit for the greatest number of people, Indonesian Pancasila values

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Authors: Jacolien Barnard, Corlia Van Heerden

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Effective and accessible consensual dispute resolution and in particular alternative dispute resolution, are central to consumer protection legislation. In this regard, the Consumer Protection Act 68 of 2008 (CPA) of South Africa is no exception. Due to the nature of consumer disputes, alternative dispute resolution (in theory) is an effective vehicle for the adjudication of disputes in a timely manner avoiding overburdening of the courts. The CPA sets down as one of its core purposes the provision of ‘an accessible, consistent, harmonized, effective and efficient system of redress for consumers’ (section 3(1)(h) of the CPA). Section 69 of the Act provides for the enforcement of consumer rights and provides for the National Consumer Commission to be the Central Authority which streamlines, adjudicates and channels disputes to the appropriate forums which include Alternative Dispute Resolution Agents (ADR-agents). The purpose of this paper is to analyze the regulation of these enforcement and redress mechanisms with particular focus on the Central Authority as well as the ADR-agents and their crucial role in successful and efficient adjudication of disputes in South Africa. The South African position will be discussed comparatively with the European Union (EU) position. In this regard, the European Union (EU) Directive on Alternative Dispute Resolution for Consumer Disputes (2013/11/EU) will be discussed (The ADR Directive). The aim of the ADR Directive is to solve contractual disputes between consumers and traders (suppliers or businesses) regardless of whether the agreement was concluded offline or online or whether or not the trader is situated in another member state (Recitals 4-6). The ADR Directive provides for a set of quality requirements that an ADR body or entity tasked with resolving consumer disputes should adhere to in member states which include regulatory mechanisms for control. Transparency, effectiveness, fairness, liberty and legality are all requirements for a successful ADR body and discussed within this chapter III of the Directive. Chapters III and IV govern the importance of information and co-operation. This includes information between ADR bodies and the European Commission (EC) but also between ADR bodies or entities and national authorities enforcing legal acts on consumer protection and traders. (In South Africa the National Consumer Tribunal, Provincial Consumer Protectors and Industry ombuds come to mind). All of which have a responsibility to keep consumers informed. Ultimately the papers aims to provide recommendations as to the successfulness of the current South African position in light of the comparative position in Europe and the highlight the importance of proper regulation of these redress and enforcement institutions.

Keywords: alternative dispute resolution, consumer protection law, enforcement, redress

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Authors: Renata Hrecska

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This research seeks to fully examine the internal employment law of international organizations by comparing it with the characteristics of the national civil service. The aim of the research is to compare the legal system that has developed over many centuries and the relatively new internal staffing regulations to find out what solution schemes can help each other through mutual legal development in order to respond effectively to the social challenges of everyday life. Generally, the rules of civil service of any country or international entity have in common that they have, in their pragmatics inherently, the characteristic that makes them serving public interests. Though behind the common base there are many differences: there is the clear fragmentation of state regulation and the unity of organizational regulation. On the other hand, however, this difference disappears to some extent: the public service regulation of international organizations can be considered uniform until we examine it within, but not outside an organization. As soon as we compare the different organizations we may find many different solutions for staffing regulations. It is clear that the national civil service is a strong model for international organizations, but the question may be whether the staffing policy of international organizations can serve the national civil service as an example, too. In this respect, the easiest way to imagine a legislative environment would be to have a single comprehensive code, the general part of which is the Civil Service Act itself, and the specific part containing specific, necessarily differentiating rules for each layer of the civil service. Would it be advantageous to follow the footsteps of the leading international organizations, or is there any speciality in national level civil service that we cannot avoid during regulating processes? In addition to the above, the personal competencies of officials working in international organizations and public administrations also show a high degree of similarity, regardless of the type of employment. Thus, the whole public service system is characterized by the fundamental and special values that a person capable of holding a public office must be able to demonstrate, in some cases, even without special qualifications. It is also interesting how we can compare the two spheres of employment in light of the theory of Lawyer Louis Brandeis, a judge at the US Supreme Court, who formulated a complex theory of profession as distinguished from other occupations. From this point of view we can examine the continuous development of research and specialized knowledge at work; the community recognition and social status; that to what extent we can see a close-knit professional organization of altruistic philosophy; that how stability grows in the working conditions due to the stability of the profession; and that how the autonomy of the profession can prevail.

Keywords: civil service, comparative law, international organizations, regulatory systems

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Authors: Ekta Yadav, Sukanta Bhattacharya, Brijesh Yadav, Ariel Hus, Jagjit Yadav

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Background and Significance: Respiratory exposure to toxicants (chemicals or particulates) causes disruption of lung homeostasis leading to lung toxicity/injury manifested as pulmonary inflammation, edema, and/or other effects depending on the type and extent of exposure. This emphasizes the need for investigating toxicant type-specific mechanisms to understand therapeutic targets. Aquaporins, aka water channels, are known to play a role in lung homeostasis. Particularly, the two major lung aquaporins AQP5 and AQP1 expressed in alveolar epithelial and vasculature endothelia respectively allow for movement of the fluid between the alveolar air space and the associated vasculature. In view of this, the current study is focused on understanding the regulation of lung aquaporins and other targets during inhalation exposure to toxic chemicals (Cigarette smoke chemicals) versus toxic particles (Carbon nanoparticles) or co-exposures to understand their relevance as markers of injury and intervention. Methodologies: C57BL/6 mice (5-7 weeks old) were used in this study following an approved protocol by the University of Cincinnati Institutional Animal Care and Use Committee (IACUC). The mice were exposed via oropharyngeal aspiration to multiwall carbon nanotube (MWCNT) particles suspension once (33 ugs/mouse) followed by housing for four weeks or to Cigarette smoke Extract (CSE) using a daily dose of 30µl/mouse for four weeks, or to co-exposure using the combined regime. Control groups received vehicles following the same dosing schedule. Lung toxicity/injury was assessed in terms of homeostasis changes in the lung tissue and lumen. Exposed lungs were analyzed for transcriptional expression of specific targets (AQPs, surfactant protein A, Mucin 5b) in relation to tissue homeostasis. Total RNA from lungs extracted using TRIreagent kit was analyzed using qRT-PCR based on gene-specific primers. Total protein in bronchoalveolar lavage (BAL) fluid was determined by the DC protein estimation kit (BioRad). GraphPad Prism 5.0 (La Jolla, CA, USA) was used for all analyses. Major findings: CNT exposure alone or as co-exposure with CSE increased the total protein content in the BAL fluid (lung lumen rinse), implying compromised membrane integrity and cellular infiltration in the lung alveoli. In contrast, CSE showed no significant effect. AQP1, required for water transport across membranes of endothelial cells in lungs, was significantly upregulated in CNT exposure but downregulated in CSE exposure and showed an intermediate level of expression for the co-exposure group. Both CNT and CSE exposures had significant downregulating effects on Muc5b, and SP-A expression and the co-exposure showed either no significant effect (Muc5b) or significant downregulating effect (SP-A), suggesting an increased propensity for infection in the exposed lungs. Conclusions: The current study based on the lung toxicity mouse model showed that both toxicant types, particles (CNT) versus chemicals (CSE), cause similar downregulation of lung innate defense targets (SP-A, Muc5b) and mostly a summative effect when presented as co-exposure. However, the two toxicant types show differential induction of aquaporin-1 coinciding with the corresponding differential damage to alveolar integrity (vascular permeability). Interestingly, this implies the potential of AQP1 as a differential marker of toxicant type-specific lung injury.

Keywords: aquaporin, gene expression, lung injury, toxicant exposure

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Authors: Nazari Maryam, Gorji Saman

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For most competitions, athletes usually engage in a process called rapid weight loss (RWL) and subsequent rapid weight gain (RWG) in the days preceding the event. Besides the perfection of performance, weight regulation mediates a self-image of being “a real athlete” which is mentally important as a part of the pre-competition preparation. This feeling enhances the focus and commitment of the athlete. There is a large body of evidence that weight loss, particularly in combat sports, results in several health benefits. However, intentional weight loss beyond normal levels might have unknown negative special effects on the immune system. As the results show, a high prevalence (50%) of RWL is happening among combat athletes. It seems that energy deprivation and intense exercise to reach RWL results in altered blood cell distribution through modification of body composition that, in turn, changes B and T-Lymphocyte and/or CD4 T-Helper response. Moreover, it may diminish IgG antibody levels and modulate IgG glycosylation after this course. On the other hand, some studies show suppression of signaling and regulation of IgE antibody and chemokine production are responsible for immunodeficiency following a period of low-energy availability. Some researchers hypothesize that severe glutamine depletion, which occurs during exercise and calorie restriction, is responsible for this immune system weakness. However, supplementation by this amino acid is not prescribed yet. Therefore, weight loss is achieved not only through chronic strategies (body fat losses) but also through acute manipulations prior to competition should be supervised by a sports nutritionist to minimize side effects on the immune system and other body systems.

Keywords: athletes, immune system, rapid weight loss, weight loss strategies

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Authors: Inga Žukovaitė

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This paper aims to present postdoc research on remote criminal proceedings in court. In this period, when most countries have introduced the possibility of remote criminal proceedings in their procedural laws, it is not only possible to identify the weaknesses and strengths of the legal regulation but also assess the effectiveness of the instrument used and to develop an approach to the process. The example of some countries (for example, Italy) shows, on the one hand, that criminal procedure, based on orality and immediacy, does not lend itself to easy modifications that pose even a slight threat of devaluation of these principles in a society with well-established traditions of this procedure. On the other hand, such strong opposition and criticism make us ask whether we are facing the possibility of rethinking the traditional ways to understand the safeguards in order to preserve their essence without devaluing their traditional package but looking for new components to replace or compensate for the so-called “loss” of safeguards. The reflection on technological progress in the field of criminal procedural law indicates the need to rethink, on the basis of fundamental procedural principles, the safeguards that can replace or compensate for those that are in crisis as a result of the intervention of technological progress. Discussions in academic doctrine on the impact of technological interventions on the proceedings as such or on the limits of such interventions refer to the principles of criminal procedure as to a point of reference. In the context of the inferiority of technology, scholarly debate still addresses the issue of whether the court will not gradually become a mere site for the exercise of penal power with the resultant consequences – the deformation of the procedure itself as a physical ritual. In this context, this work seeks to illustrate the relationship between remote criminal proceedings in court and the principle of immediacy, the concept of which is based on the application of different models of criminal procedure (inquisitorial and adversarial), the aim is to assess the challenges posed for legal regulation by the interaction of technological progress with the principles of criminal procedure. The main hypothesis to be tested is that the adoption of remote proceedings is directly linked to the prevailing model of criminal procedure, arguing that the more principles of the inquisitorial model are applied to the criminal process, the more remote criminal trial is acceptable, and conversely, the more the criminal process is based on an adversarial model, more the remote criminal process is seen as incompatible with the principle of immediacy. In order to achieve this goal, the following tasks are set: to identify whether there is a difference in assessing remote proceedings with the immediacy principle between the adversarial model and the inquisitorial model, to analyse the main aspects of the regulation of remote criminal proceedings based on the examples of different countries (for example Lithuania, Italy, etc.).

Keywords: remote criminal proceedings, principle of orality, principle of immediacy, adversarial model inquisitorial model

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Authors: Avent Grange, Frederic Bertrand, Jean-Baptiste Droin, Amandine Marrel, Jean-Henry Ferrasse, Olivier Boutin

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CEA and its industrial partners are designing a gas Power Conversion System (PCS) based on a Brayton cycle for the ASTRID Sodium-cooled Fast Reactor. Investigations of control and regulation requirements to operate this PCS during operating, incidental and accidental transients are necessary to adapt core heat removal. To this aim, we developed a methodology to optimize the thermal-hydraulic behavior of the reactor during normal operations, incidents and accidents. This methodology consists of a multi-objective optimization for a specific sequence, whose aim is to increase component lifetime by reducing simultaneously several thermal stresses and to bring the reactor into a stable state. Furthermore, the multi-objective optimization complies with safety and operating constraints. Operating, incidental and accidental sequences use specific regulations to control the thermal-hydraulic reactor behavior, each of them is defined by a setpoint, a controller and an actuator. In the multi-objective problem, the parameters used to solve the optimization are the setpoints and the settings of the controllers associated with the regulations included in the sequence. In this way, the methodology allows designers to define an optimized and specific control strategy of the plant for the studied sequence and hence to adapt PCS piloting at its best. The multi-objective optimization is performed by evolutionary algorithms coupled to surrogate models built on variables computed by the thermal-hydraulic system code, CATHARE2. The methodology is applied to a loss of off-site power sequence. Three variables are controlled: the sodium outlet temperature of the sodium-gas heat exchanger, turbomachine rotational speed and water flow through the heat sink. These regulations are chosen in order to minimize thermal stresses on the gas-gas heat exchanger, on the sodium-gas heat exchanger and on the vessel. The main results of this work are optimal setpoints for the three regulations. Moreover, Proportional-Integral-Derivative (PID) control setting is considered and efficient actuators used in controls are chosen through sensitivity analysis results. Finally, the optimized regulation system and the reactor control procedure, provided by the optimization process, are verified through a direct CATHARE2 calculation.

Keywords: gas power conversion system, loss of off-site power, multi-objective optimization, regulation, sodium fast reactor, surrogate model

Procedia PDF Downloads 281