Letteratura scientifica selezionata sul tema "Co-regulators"

Background and Aim: The incidence of nonalcoholic fatty liver disease (NAFLD), ranging from mild steatosis to hepatocellular injury and inflammation, increases with the rise of obesity. However, the implications of transcription factors network in progressive NAFLD remain to be determined. Methods: A co-regulatory network approach by combining gene expression and transcription influence was utilized to dissect transcriptional regulators in different NAFLD stages. In vivo, mice models of NAFLD were used to investigate whether dysregulated expression be undertaken by transcriptional regulators. Results: Through constructing a large-scale co-regulatory network, sample-specific regulator activity was estimated. The combinations of active regulators that drive the progression of NAFLD were identified. Next, top regulators in each stage of NAFLD were determined, and the results were validated using the different experiments and bariatric surgical samples. In particular, Adipocyte enhancer-binding protein 1 (AEBP1) showed increased transcription activity in nonalcoholic steatohepatitis (NASH). Further characterization of the AEBP1 related transcription program defined its co-regulators, targeted genes, and functional organization. The dynamics of AEBP1 and its potential targets were verified in an animal model of NAFLD. Conclusions: This study identifies putative functions for several transcription factors in the pathogenesis of NAFLD and may thus point to potential targets for therapeutic interventions.

Abstract Recent reforms have given regulators broad powers to “bail-in” bank creditors during financial crises. We analyze efficient bail-ins and their implementation. To preserve liquidity, regulators must avoid signaling negative private information to creditors. Therefore, optimal bail-ins in bad times only depend on public information. As a result, the optimal policy cannot be implemented if regulators have wide discretion, due to an informational time-inconsistency problem. Rules mandating tough bail-ins after bad public signals, or contingent convertible (co-co) bonds, improve welfare. We further show that bail-in and bailout policies are complementary: if bailouts are possible, then discretionary bail-ins are more effective.

Estrogen-related receptors (ERRα, β and γ in mammals) are orphan members of the nuclear receptor superfamily acting as transcription factors. ERRs are expressed in several cell types and they display various functions in normal and pathological contexts. Amongst others, they are notably involved in bone homeostasis, energy metabolism and cancer progression. In contrast to other nuclear receptors, the activities of the ERRs are apparently not controlled by a natural ligand but they rely on other means such as the availability of transcriptional co-regulators. Here we focus on ERRα and review the variety of co-regulators that have been identified by various means for this receptor and their reported target genes. ERRα cooperates with distinct co-regulators to control the expression of distinct sets of target genes. This exemplifies the combinatorial specificity of transcriptional regulation that induces discrete cellular phenotypes depending on the selected coregulator. We finally propose an integrated view of the ERRα transcriptional network.

ABSTRACTEuropean networks of regulators in industries such as telecommunications, securities, energy and transport have been cited as important examples of the growth of network governance in Europe. Using a principal-agent perspective as a starting point, the article examines why a double delegation to networks of regulators has taken place. It looks at how and why the European Commission, national governments and independent regulatory agencies have driven the creation of networks, their institutional character and their implications for regulatory governance in Europe. It argues that problems of co-ordination were the main factor advanced to justify establishing networks of regulators. The new networks have been given a wide range of tasks and broad membership, but enjoy few formal powers or resources. They are highly dependent on the European Commission and face rivals for the task of co-ordinating European regulators. Thus in institutional terms the spread of network governance has in fact been limited.

Background: It is unclear why AQP4-IgG primarily causes central nervous system lesions by activating complement, but generally spares peripheral AQP4-expressing organs. Objectives: To determine whether peripheral AQP4-expressing cells are protected from complement-mediated damage by expressing complement regulators. Methods: Human tissue and cultured human cells were immunostained for aquaporin-4 (AQP4), CD46, CD55 and CD59. We also determined the vulnerability to AQP4-IgG and complement-mediated damage of astrocytes cultured alone or co-cultured with endothelial cells. Results: In normal brain, astrocyte end-feet express AQP4, but are devoid of CD46, CD55 and CD59. Immunoreactivity for CD46, CD55 and CD59 is not increased in or around neuromyelitis optica lesions. In kidney AQP4 is co-expressed with CD46 and CD55, in stomach AQP4 is co-expressed with CD46 and in skeletal muscle AQP4 is co-expressed with CD46. Astrocytes cultured alone co-express AQP4 and CD59 but, in astrocyte-endothelial co-cultures, AQP4 is found in cell processes devoid of CD59. Astrocytes co-cultured with endothelial cells are more vulnerable to AQP4-IgG and complement-mediated lysis than astrocytes cultured alone. Conclusions: Complement regulators protect peripheral organs, but not the central nervous system, from AQP4-IgG and complement-mediated damage. Our findings may explain why neuromyelitis optica primarily damages the central nervous system, but spares peripheral organs.

We determined the protein expression of adipogenic transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ) and its co-repressor and co-activator complexes in adipose tissue from the obese offspring of under- and over-nourished dams. Female rats were fed either a high-fat (60% kcal) or control (10% kcal) diet before mating, and throughout pregnancy and lactation (Mat-OB). Additional dams were 50% food-restricted from pregnancy day 10 to term [intrauterine growth-restricted (IUGR)]. Adipose tissue protein expression was analyzed in newborn and adult male offspring. Normal birth weight Mat-OB and low birth weight IUGR newborns had upregulated PPARγ with variable changes in co-repressors and co-activators. As obese adults, Mat-OB and IUGR offspring had increased PPARγ with decreased co-repressor and increased co-activator expression. Nutritionally programmed increased PPARγ expression is associated with altered expression of its co-regulators in the newborn and adult offspring. Functional studies of PPARγ co-regulators are necessary to establish their role in PPARγ-mediated programmed obesity.

Thesis (Ph.D.)--Boston University PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.
Type I collagen overexpression is a major contributor to fibrosis. This thesis investigates the function of two transcriptional co-regulator complexes involved in collagen expression. Interferon γ induces class II transactivator (CIITA), which is a potent activator of major histocompatibility class (MHC) II expression while concomitantly repressing collagen transcription. It was hypothesized that mutation of CIITA would alter the immune response and increase collagen transcription during bleomycin-induced fibrosis. Two CIITA partial knockout strains had decreased macrophage and T cell recruitment after bleomycin injury. Compared to WT, mutant CIITA mice had elevated IL-4 and IL-10 cytokine expression coinciding with decreased lung disease. Since CIITA hypomorphic mice maintained the collagen repression domain, there was equivalent fibrosis as judged by morphology and biochemical quantification of collagen. These studies determined that CIITA mediates injury and inflammatory responses in the lung. Myofibroblasts, characterized by the expression of smooth muscle cell actin (SMA) and collagen, are important regulators of the repair of tissue injury and fibrosis progression. The transcriptional co-activator, myocardin related transcription factor A (MRTF-A) is known to regulate SMA gene expression. It was hypothesized that MRTF-A might also activate expression of type I collagen in fibrotic cells. MRTF-A strongly transactivated type I collagen gene reporters in lung fibroblasts. Expression of a dominant negative MRTF-A or shRNA targeting MRTF-A resulted in a significant reduction in type I collagen synthesis. MRTF-A is known to activate gene transcription via serum response factor (SRF), which binds to CArG boxes within responsive promoters. Analysis of the COL1A2 promoter revealed a non-canonical CArG box [CCAAACTTGG] as well as several specific protein 1 (Sp1) sites that were important for MRTF-A activation. Fibroblasts from MRTF-A knockout mice exhibited impaired myofibroblast differentiation compared to WT controls. These findings indicate that MRTF-A is an important regulator of collagen synthesis in lung fibroblasts and it depends on both SRF and Sp1 to enhance collagen expression. Taken together, these studies identified two important transcriptional co-regulator complexes with potential regulatory roles in lung fibrosis.

Abstract One of the major tasks in cancer research is to understand the regulation of transcription factors that are crucial in controlling cell proliferation, differentiation and apoptosis. To achieve this, transcriptional co-regulators and signaling pathways that control transcription factors have been extensively studied. One good example is the Runx family of proteins and two of their co-regulators, transcription co-activator with PDZ domain-binding motif (TAZ) and Yes-associated protein (YAP). TAZ and YAP are paralogous and serve as either co-activators or co-repressors depending on the cellular context. In an attempt to understand the underlying molecular mechanisms for this dual role in transcription regulation, and especially considering that Yorkie (a Drosophila homologue of YAP) is under control of the hippo kinase pathway, we considered the possibility that TAZ and YAP are the target of this pathway. As such, we sought to test the signaling pathways, including the hippo-like pathway, that regulate the function of TAZ and YAP in mammalian cells. In this thesis research, I first set out to characterize how TAZ, in synergy with the histone acetyltranserase monocytic leukemia zinc finger protein (MOZ), activates Runx-dependent transcription in a signal-responsive manner. Then I used Runx-dependent transcription as a model system to study the regulation of TAZ. I found that both class I and II histone deacetylases interacted with TAZ and repressed its co-activator activity. In addition, TAZ is acetylated by and synergizes with CBP and p300, two paralogous acetyltransferases, to activate transcription. These results suggest that the activity of TAZ is subjected to regulation by acetylation and deacetylation. These results also provide a molecular basis for the hypothesis that TAZ and YAP recruit or release co-repressors in response to cellular stimuli. I then investigated the hippo-like pathway in mammalian cells. Excitingly, I found that the ki
Résumé Un des défis majeurs de la recherche sur le cancer est de comprendre la régulation de certains facteurs de transcription qui jouent un rôle clé dans le contrôle de la prolifération, de la différenciation et de l'apoptose. Pour cette raison, de nombreuses études approfondies sur les corégulateurs et les voies de signalisation ont été menées. Parmi celles-ci, la famille des protéines Runx et deux de leurs corégulateurs, TAZ (transcription co-activator with PDZ domain-binding motif) et YAP (Yes-associated protein) en sont un bon exemple. TAZ et YAP sont des protéines paralogues et agissent comme des coactivateurs ou des corepresseurs en fonction du contexte cellulaire. Puisque Yorkie, l'orthologue de YAP chez la drosophile, est contrôlé par la voie de signalisation de hippo, l'identification de celle qui régule les fonctions de TAZ et de YAP dans les cellules de Mammifères a été menée afin de comprendre les mécanismes moléculaires du double rôle de ces corégulateurs dans la régulation transcriptionnelle. Dans ce travail de thèse, la manière dont TAZ active la transcription dépendante de Runx, en synergie avec l'histone acétyltransférase MOZ (monocytic leukemia zinc finger protein) a été étudiée. Par la suite, la transcription médiée par Runx a été utilisée comme modèle afin d'étudier la régulation de TAZ. Il a ainsi été démontré que les histones deacétylases de classe I et II interagissent avec TAZ et répriment son activité de coactivateur dans la transcription dépendante de Runx. En outre, TAZ est acétylé par CBP/p300, deux acétyltransférases paralogues, et synergise avec ces deux protéines pour activer la transcription. Ces résultats suggèrent donc que l'activité de TAZ est régulée par un mécanisme d'acétylation et de déacétylation et que TAZ et YAP recrutent et relâchent des corépresseurs en réponse à différents stimuli cellulaires. À la lumière de ces informations, la voie de sig

Le muscle squelettique (MS) est un tissu métabolique important. L'objectif de ma thèse était de caractériser le rôle des corégulateurs de la transcription, PGC-1β (transcriptional coactivator peroxisome proliferator-activated receptor-gammacoactivator 1beta) et TIF2 (Transcriptional Intermediary Factor 2) dans ce tissu. Mon travail a démontré que PGC-1β limite le stress oxydatif est crucial dans le maintien de la structure et de la fonction mitochondriale, via le contrôle de l’expression de gènes impliqués dans les voies de signalisation liées à l’énergie, à la dynamique mitochondriale et à la machinerie d’import mais n'est pas indispensable pour le contenu mitochondrial. Mon travail aussi démontré que TIF2 de la MS a un impact négatif sur la durée de vie des mammifères. De plus, la déplétion de TIF2 conduit à une protection partielle du MS contre les dommages oxydatifs induits par le stress. Ainsi notre travail représente une avancée dans l’établissement futur de traitements contre les troubles liés au stress oxydatif et au vieillissement
Skeletal muscle (SM) accounting for ~ 40% of total body mass is an important metabolic tissue. The aim of my thesis was to characterize the role of transcriptional coregulators, peroxisome proliferator-activated receptor-gamma coactivator-1β (PGC-1β) and transcriptional intermediary factor 2 (TIF2) in this tissue. My work demonstrated that PGC-1β is crucial to maintain SM mitochondrial structure and function, by controlling expression of genes involved in energy pathways, mitochondrial dynamics and import machinery, but is dispensable for mitochondrial content and fiber type maintenance. Furthermore, it limits oxidative stress. The second part of my work demonstrated that myofiber TIF2 has negative impact onmammalian life span. Moreover, TIF2 ablation leads to partial protection of SM from oxidative stress-induced damage. In conclusion, our work provides a better understanding of SM homeostasis regulation and insights in treatments for disordersrelated to oxidative stress and aging

Thesis (Ph. D.) -- University of Maryland, College Park, 2004.
Thesis research directed by: Molecular and Cell Biology. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.

Thesis (M.S.)--University of California, San Diego, 2009.
Title from first page of PDF file (viewed September 15, 2009). Available via ProQuest Digital Dissertations. Includes bibliographical references (p. 58-61).

The subject matter of this thesis is a regulatory innovation termed co-regulation: a mode of regulation that includes formal involvement of both state and non-state actors. Its emergence and development is the result of two broad and significant changes in the nature of the statehood: the emergence of the regulatory state and the shift from government to governance. In the regulatory state, the dominant mode of intervention in economy and society is regulation, thus forms such as co-regulation are used to ‘govern’ or ‘steer’ the society. In addition, with the shift to governance, there is a greater reliance on non-state actors to perform this ‘steering’. Since co-regulation is used to implement public policy objectives, which has traditionally been the role of government departments, but it implies formalized and substantive role of non-state actors, it is a qualitatively new regulatory development that justifies research interest into its nature. Consequently, it should be evaluated as any other form of governance: to what extent it can be described as democratic, and precisely this is the basis for the normative framework developed for this thesis that has been used as a tool to evaluate the nature and quality of co-regulation. One of the basic premises of this research is that any form of governance should have as its ultimate goal the achievement of public interest objectives. It has been further argued that public interest objectives can be achieved only if institutional structures of regulatory bodies enable transparency, deliberative participation by the citizens, and enable citizens to hold the regulators to account. Only by providing such structures, co-regulatory bodies would empower the citizens to be the ultimate authority and could thus be considered a democratic form of governance. The case studies chosen to evaluate whether this normative ideal has been achieved in practice comprise three different bodies: Ofcom, ASA and ATVOD. What has in particular been looked at is the way Ofcom handled the delegation of regulatory functions to ASA and ATVOD, and the way these bodies dealt with the regulation of 3 alcohol ads and product placement. These studies involve an element of controversy and conflicting interests and as such represent the most suitable test in order to determine whether the possibilities offered by co-regulation to be a truly democratic form of governance have been achieved. The main conclusion reached is that, mainly due to NPM reforms, citizens are confined to the role of the consumers, where their active engagement is seen in terms of complaints and regulators are held accountable for the level of service they provide in handling these complaints. However, this does not empower the citizens. Therefore, it appears that Ofcom, ASA and ATVOD are not characterized by institutional structures that would enable democratic governance: there are no transparent institutional structures that would enable the public to perform the role of the citizens and deliberate regarding regulatory decisions and hold Ofcom, ASA and ATVOD to account. The institutional structures modelled on the premises of corporate governance are not empowering citizens, but are instead creating consumers.

This chapter explores the different ways in which market actors are “co-opted” as corporate law regulators. It considers the preconditions for generating “endogenous self-regulation” through the lens of the formation and operation of the UK Takeover Code and Panel. From endogenous self-regulation, the chapter moves onto consider “market-controlled” regulation where the state directly co-opts market actors as regulators. The chapter shows that the regulatory biases generated by self-regulation are more multi-faceted than, and often inconsistent with, the standard account that self-regulation is likely to generate rules that favour the regulated.

This chapter focuses on the functions of the Prudential Regulation Authority (PRA) and the Financial Conduct Authority (FCA) as statutory regulators of the financial services sector in the UK. It begins with a discussion of the constitutional provisions establishing the FCA and the PRA by virtue of the Financial Services and Markets Act 2000 (FSMA). It then considers the remit of the FCA and the PRA, along with their general functions and duties, statutory objectives, and regulatory principles with respect to financial services regulation. It also examines the boundary between FCA and PRA responsibilities, arrangements for the supervision of regulated firms and for enforcement, and the co-ordination between the FCA and the PRA in the exercise of their function. Finally, it describes the PRA's power of direction, directions relating to consolidated supervision, and central government and Parliamentary oversight of the regulators.

EU law recognizes the regulatory role of social partners—the bodies representing management and labour—but provides neither a legal nor a fully developed conceptual framework. An output analysis of the texts produced by the social partners demonstrates that they fulfil a variety of functions, both as stakeholders and co-regulators. However, only a small percentage of the documents produced in the European social dialogue have the status of EU collective agreements. It is the latter group which is most interesting from the point of view of regulation. A further analysis tracks the different interactions between EU law and EU collective agreements and highlights the tension between horizontal and vertical subsidiarity created by the REFIT agenda.

Key points• Older people, often with high levels of co-morbidity and polypharmacy, are increasing in number as the population ages.• Study populations in clinical trials have often not mirrored the population that will consume the drugs or treatments being investigated.• Regulators, ethics committees, and funding bodies must recognize the need for inclusion of older people and the complexities this imposes on investigators.• Across all aspects of medicine, funding for research into how best to safely include older people in clinical trials is vital.• Researchers should not be disadvantaged by designing studies to meet the needs of the age range of patients expected to receive the treatment being investigated; this should include provision for older people.

Privatization began in the 1970s with Carter's deregulation of some business, and increased with the Thatcher administration in the United Kingdom, the Reagan administration in the United States, and many communist and socialist countries. One area of concern in privatization is transportation—airports, water ports, roads, and mass transit. Privatization can be implemented in financing, construction, operation, and maintenance of the transportation system, the main motives being the belief that the private sector can be more efficient than the public sector, and because public funds are becoming less plentiful for a variety of reasons. The focus is on ideas and innovations for expanding the private role in transportation. Specifically covered are ideas and innovations for expanding the role of private sector in U.S. transportation projects, private financing of urban transportation, airport privatization, water port improvement, toll roads, and competitive contracting for transit services. The distinguished list of contributors includes the co-recipient of the 1996 Nobel Prize in Economics, William Vickrey. The audience for the work are scholars dealing with the discussions concerning the economics and politics of privatization, business people who are likely to be interested in potential opportunities, governmental regulators and staff, and policy makers.

Fibroblast growth factor 23 (FGF23) and Klotho have emerged as major hormonal regulators of phosphorus (P) and vitamin D metabolism. FGF23 is secreted by bone cells and acts in the kidneys to increase urinary P excretion and inhibit the synthesis of 1,25 dihydroxyvitamin D (1,25(OH)2D) and in the parathyroid glands to inhibit the synthesis and secretion of parathyroid hormone. Phosphorus excess stimulates FGF23 secretion, likely as an appropriate physiological adaptation to maintain normal P homeostasis by enhancing urinary P excretion and diminishing intestinal P absorption via lower 1,25(OH)2D. The FGF23 concentrations are elevated early in the course of chronic kidney disease (CKD) and may be a primary initiating factor for the development of secondary hyperparathyroidism in this setting. Klotho exists in two forms: a transmembrane form and a secreted form, each with distinct functions. The transmembrane form acts as the key co-factor needed for FGF23 to bind to and activate its cognate receptor in the kidneys and the parathyroid glands. The secreted form of Klotho has FGF23-independent effects on renal P and calcium handling, insulin sensitivity, and endothelial function. Disturbances in the expression of Klotho may play a role in the development of altered bone and mineral metabolism in early CKD. In addition, abnormal circulating concentrations of both FGF23 and Klotho have been linked to excess cardiovascular disease, suggesting that both play an important role in maintaining cardiovascular health.

AbstractThe three chapters in this Part reflect on their authors’ respective experiences of the challenges presented by the realpolitik of implementing projects in values-based practice. The challenges reflect the ‘3 Rs’ of values-based practice by which (as described in our concluding chapter 47, “Co-writing Values: What We Did and Why We Did It”) we have been guided in developing this book: Raising awareness, chapter 44, “Reflections on the Impact of Mental Health Ward Staff Training in Race Equality and Values-Based Practice”, a project combining race equality training and values-based practice for ward staff; Recognition, chapter 45, “Connecting Patients, Practitioners and Regulators in Supporting Positive Experiences and Processes of Shared Decision-Making in Osteopathy: A Case Study in Co-production”, a project in positive practice bringing together regulators, clinicians and patients; and Respect, chapter 46, “Beyond the Colour Bar: Sharing Narratives in Order to Promote a Clearer Understanding of Mental Health Issues Across Cultural and Racial Boundaries”, a project aimed at getting beyond the colour bar between white and black in mental health diagnosis. The chapter concludes with a note on the significance of the resources available from a culturally enriched form of values-based mental health practice for meeting the challenges of implementation.

AbstractThis chapter describes a project in osteopathy exploring how regulators can support shared decision-making by positively promoting good practice rather than by way of traditionally adopted methods based on fitness to practice and disciplinary action. The project is built in part on a background development programme in values-based osteopathy. The regulator (the General Osteopathic Council), osteopaths and patients worked together co-productively in a series of workshops to develop support resources for shared decision-making based on what is important to the individual patient in question. Central to the project was an emerging understanding of the cultural values of osteopathy as a profession and how these impact on their practice. A summary of and links to the resources produced by the project are included. The chapter starts with a case narrative (the story of ‘Jennifer’) adapted from one used in the background development programme.

The conclusion of contracts was known in ancient times and is still relevant today. Shares that are not distributed in kind can cause certain difficulties that force the interested parties to decide on distribution.Joint ownership of inherited property received from a family member necessitates joint decision-making on its maintenance, ownership, use, and disposal, and it is difficult to achieve such a consensus on all issues. Therefore, quite often a certain period may pass from the acquisition of the right to a share in the joint property to its distribution, but due to conflicts regarding the use of the property or in the case of the need to receive funds or for other reasons, the joint property is divided by the co-owners. That is, the reasons may even be questions of how to use agricultural land, for example, to rent it out, sow it yourself, plant a garden, etc. However, the complexity of the division of land plots is because it is difficult to «divide» agricultural lands at least. After all, their intended use depends on the size, etc. Quite often, disputes also arise regarding the use of residential buildings, since the size and location of the rooms make their use impossible or difficult, as well as the distribution in kind according to the inherited shares. In other words, there is a certain «trading» of assets. If the situation is related to the distribution of a small plot of land where the house is located, then questions also arise regarding the establishment of an easement, as well as mutual concessions for the compensation of a part of the house in exchange for most of the land. In general, there are protracted negotiations, from the point of view of which these parties, who are still in a family relationship, agree on the division of property.Factors that can affect the outcome of property division include unique family circumstances, the specific nature of assets, and traditional legal practices. The parties will use different mechanisms for the division of joint assets: sale, donation, or exchange, under the terms of which they «trade» with the consent of others their rights as co-owners of jointly owned objects. The various evolutionary stages of the agreement on the division of property by the testator’s family culminate in the final stage of agreeing. The agreement on the division of inheritance is a complex legal process. Potentially, in a single transaction, the beneficiaries can choose and implement the division by sale, exchange, or donation. These different legal constructions reflect the uniqueness of the decisions in each agreement and to some extent demonstrate the specific legal practice of the individual Old Babylonian city-state and the particular circumstances of each family.However, in addition to the division of property, there are other agreements regarding the division of inheritance. For example, an agreement on quasi-partition upon adoption (quasi-adoption), an agreement on the division of residential property by the owner between its future beneficiaries.The need to conclude such agreements arises when an agreement on the division of property is required, which differs from such concepts as sale, donation, exchange, etc.Domestic scientists consider the agreement on the distribution of joint property very broadly and include other types of agreements in the list of such agreements, establishing that the agreement on changing the succession of the right to inheritance by law is atypical. It was determined that the contract under investigation belongs to contracts on the distribution of inheritance. Agreements on the distribution of inheritance are concluded in the field of inheritance, which indicates that they belong to inheritance agreements. It is proposed to supplement the existing classifications of civil law contracts by distinguishing a new type of civil law contracts – contracts in the law of inheritance on the level with the selection of a new type of inheritance contracts – contracts on the distribution of inheritance.» This is a bold hypothesis, but it is difficult to agree with it for various reasons, not least because the distribution of inheritance has been known since ancient times.The factor that the term «distribution» of inheritance and giving it a broad legal meaning is analyzed is an interesting author’s hypothesis. At the same time, according to our position, the term «distribution of inheritance» is more balanced, since in Art. 1278 of the Civil Code does not quite successfully use the term «division», when in the content of this norm it is about the equality of shares in the inheritance and the allocation of a share in kind, and not about division. However, in Part 1 of Art. 1280 of the Civil Code, the term «distribution» is used with a direct meaning and «redistribution» as an opportunity to review the results of the distribution under new circumstances – in the case of acceptance of the inheritance by other heirs. In essence, the obvious meaning of the term «distribution» follows from this norm as the initial determination of the ownership of the share of each of the heirs. In this sense, the redistribution of the inheritance should be connected with the possible introduction of changes to the previously made distribution, that is, in this case, we do not limit the number of subsequent redistributions of the inheritance. This hypothesis is related to the fact that the number of heirs who missed the deadline for valid reasons is not limited by legislation and cannot be limited, but is determined by various legal circumstances.Therefore, it is hardly expedient and possible, to apply in Art. 1280 of the Civil Code, the concept of «distribution» should be given a wider meaning than it has in the Civil Code, as this would lead to its ambiguous perception and application both in theory and in legislation and practice. Usually, theoretical terms should be distinguished by being original and should accurately reflect the legal meaning of actions, events, or conditions.But an important element of the procedure for the distribution of common inheritance property or its redistribution are the subjects who must fix the relevant agreement or carry out such distribution according to their conviction.It is indicated that the practice of concluding contracts by the living owner with his future heirs is widespread in foreign countries. At the same time, German experts equate inheritance with what they consider to be contractual inheritance.It should be noted that the practice of concluding contracts on the distribution of inheritance in the practice of the Ukrainian notary is relatively new and does not have clear boundaries in regulation, which complicates the activity of notaries in certifying such contracts. There are several difficulties in the application of relevant legal norms in practice, as there is a lack of understanding of the legal nature and essence of the conclusion of contracts, the term of conclusion, and the procedure for notarization.The opinions of individual authors are studied, about legal relations regarding the division of inheritance characterized by a weak state policy, this obliges the participants of such relations to draw up the content of agreements on the division of inheritance independently. For agreements between heirs on the distribution of inheritance to be valid regulators of the relations of its participants (heirs), conditions (clauses) must be clarified and formulated, which will be disclosed with sufficient completeness and consistency of the content of the relevant agreement and the purpose of its conclusion.We do not agree with this point of view of the scientist regarding «weak state policy», since the Central Committee of Ukraine was not created by politicians or the Ministry of Justice of Ukraine, but by leading scientists of Ukraine. It is also difficult to agree with the statement that the lack of clear regulation of the terms of inheritance contracts «obliges the participants of such relationships to independently draw up the content of inheritance distribution contracts.» In Ukraine, some good notaries and lawyers can draw up high-quality contracts for the distribution of inheritance. Moreover, according to Art. 4 of the Law of Ukraine «On Notaries», notaries have the right to draw up relevant draft contracts. In our opinion, it is worth emphasizing here that this is a right, not a duty of a notary public. That is, the notary may not undertake the drafting of the relevant project, but this provision is positive for interested parties since the lack of experience in drafting original contracts will most likely lead to the drafting of a low-quality draft contract. Indeed, in this case, it is worth looking for an experienced notary who will be able to draw up a draft contract, but this will make it possible to prevent errors in its drafting with a high probability.Thus, the agreement on the distribution of inheritance enters into force if the parties reach an agreement in the proper form on all the essential terms of the agreement. The main essential condition for agreeing on the division of inheritance is the subject of the agreement. However, either party may consider this condition insufficient and propose to include additional conditions in the contract. In this case, these conditions become essential. In connection with the instability of the regulation of the content of contracts between heirs on the distribution of inheritance, it can be concluded that the inclusion of normal conditions in the contract is currently impossible. We believe that such a general scheme of perception of contract terms is not entirely rational, since how to perceive ordinary terms or essential terms of a contract quite often in practice depends on the judgments of the parties to the contract unless otherwise regulated by legislation. This issue can be approached more precisely if we take into account the possibility of interpreting transactions and contracts (Article 213 of the Civil Code).So, based on the essence of the process of concluding contracts, it should be taken into account that the notary who drafts the contract can edit it, therefore it is worth recognizing the right of the notary to interpret it, since according to Art. 5 of the Law of Ukraine «On Notaries», he is obliged to clarify the legal consequences that will arise for persons after his certification. It follows from this that the notary must be given the official right to interpret the contract upon its certification, then it will be clear that after its certification, the court can interpret the content of the contract. In this regard, Art. 213 of the Civil Code is proposed to be supplemented with a corresponding provision regarding the powers of the notary, namely: his duty to interpret the content of the deed or contract before and during its certification.The Inheritance Regulation, which envisages wide acceptance of the inheritance contract, is considered. It is noted that it is worth revising Ukrainian inheritance law in advance for compliance with European standards since after Ukraine accedes to the EU it will be necessary to inform all EU countries about what types of contracts in Ukraine will be related to the issuance of the European Certificate of Succession.This is also important for inheritance by law, because, in case of non-fulfillment of the terms of the lifetime maintenance (care) agreement and the inheritance agreement, they will have to be terminated or recognized as invalid or unfulfilled by the acquirer, so the property that was the subject of this agreement will be inherited by law. At the same time, if the terms of these agreements are fulfilled, the part of the property that belonged to the testator will not be inherited but will become the property of the acquirers.The process of accepting the inheritance is quite long, and the inheritance law allows for several agreements between the heirs, which can significantly affect the size of the inheritance shares and the real things in each share in the inheritance. Therefore, it is necessary to analyze the possibility of agreements between the heirs at different stages of accepting or not accepting the inheritance. From communication with one of the clients, the author learned that the notary unofficially advised the heirs to agree on the distribution of the inheritance, as well as for certain heirs to waive the right to inheritance, but to receive a proper share of the inheritance in household items. When the author was informed of all the circumstances of the inheritance case, it became clear that the notary could not solve the complex inheritance problem, since the inheritance took place based on a will and some heirs had the right to a mandatory share, as well as part of the property remained. So, in such a situation, it was necessary to solve an arithmetical and at the same time legal problem, the complexity of which was determined by the complex subject composition of numerous heirs. Therefore, the notary tried to simplify its solution by artificially «transforming» the heirs who have the right to a mandatory share into ordinary heirs who claim property that is not subject to recording in the certificate of the right to inheritance.A natural will was considered, when the testator bequeathed the specific property to each of the heirs, namely: a house to a daughter, a factory to one son, and a yacht to another let’s say. In such a case, the will of the testator is formulated in the Shodo of the objects of inheritance, so it is difficult to perceive the consequences of the refusal of one of the heirs to inherit, when the yacht will be divided into equal shares between the son and the daughter, because: firstly, the value of the factory and the house will be different, so someone from the testator gave the children a larger inheritance than the other. Secondly, in the case of the existence of a part of the inheritance not covered by the will, it can be assumed with a high degree of probability that the will of the testator was formulated about a certain property and nothing more. Therefore, in case of refusal of one of the heirs to inherit under the will, the property bequeathed to him should be considered as not covered by the will and should be inherited according to the law. That is, if the will of the testator regarding the entire property is revealed, it can be assumed that he thus intended to deprive one of the heirs of the right to inheritance.At the same time, the will must be interpreted not only by the heirs under the will but also by the heirs under the law, when its content concerns the right to a mandatory share in the inheritance, which belongs to the heirs under the law of the first rank, who due to incapacity have the right to claim it, as well as the recipients of the response. With a high degree of probability, it can be assumed that the inheritance, which consists of household items, will be divided even without a written agreement. However, the interpretation of a will, which concerns a substantial inheritance between a significant number of heirs, requires not only a written form of recording of agreements – a contract, but also, in our opinion, a notarial form that will allow recording the agreement more reliably, to explain to the parties to the contract the consequences of its conclusion. If all interested parties sign the agreement, and the notary recognizes it as legal, then it will be difficult to recognize it as illegal or invalid in the next one. Therefore, the agreement on the interpretation of the will, which will establish the specific rights of the heirs and their obligations regarding the coverage of the testator’s debts, is a rational form of specification of the terms of the inheritance, which will allow establishing the executor of the will, if he was not determined by the testator.We can assume with a high degree of probability that similar «simplified calculations» are made by other notaries, as well as directly by the heirs, and certain agreements are not necessary here.

Abstract This chapter covers the reforms brought about by the Enterprise and Regulatory Reform Act (ERRA) to the concurrency regime, with a view to strengthening the co-operation between the CMA and the sectoral regulators (Ofcom, Ofgem, Ofwat, ORR, NIAUR, CAA, Monitor, PSR, and FCA). It discusses the fact that the sectoral regulators had, in the eyes of many observers, not used their powers to enforce competition law robustly enough. It outlines the innovations brought about by the ERRA, including conferral on the CMA of the power to decide which regulator should lead an investigation, and granting the Secretary of State the power to remove concurrent competition powers from sectoral regulators, and to make regulations on information exchange between the CMA and the regulators. There is also a discussion of the newly created UK Competition Network. The chapter concludes that the changes may have altered the balance between regulation and competition law enforcement.

Abstract Innovation is a complex process which is increasingly dependent on interfirm co-operation for the sharing of economic risks and pooling of complementary resources. Regulation of inter-firm collaboration is inherently more problematic when patent rights are involved, since the patent grant provides the holder with legal rights which sometimes extend beyond those permitted under normal competition law principles. In this chapter, I examine the requirements for innovation, including inter-firm co-operation; the potential conflicts between the objectives of the patent and competition laws; and attempt to draw insights from comparing the policies followed by competition and antitrust law. regulators in the European Community (EC) and the USA in analysing patent licensing arrangements.

Abstract This chapter explores how Chinese online platforms self-regulate in the shadow of the dynamic pyramid model of regulation. As consumers rarely resort to public institutions due to their small-value claims, platforms become de facto regulators, enforcing internal rules through various sanctioning mechanisms. Platforms leverage reputation systems, sometimes tolerating fake promotional reviews, to mitigate information asymmetry and boost user engagement. However, this also creates more conflicts, pushing platforms to improve their dispute-resolution systems. While some platforms have substantial resources for enforcing rules, others lean on state support when their punitive actions lack a legal basis or implementation capacity. This co-regulation with the judiciary aids the growth of the Chinese platform economy, acting as a “helping hand” and lending credibility to platforms’ self-regulation, contrasting with the “grabbing hand” tendency of public regulation.

Due to environmental regulations, Nitrogen oxides (NOx), Carbon Monoxide (CO) and Sulfur Dioxide (SO2) emissions are key issues for gas turbine plants. Regulators are becoming more and more involved and they often require complete and real-time emission information. The measurements can be done with gas analyzers, this technology is called CEMS: Continuous Emissions Monitoring System. An alternative method [1][2] is to use a calculation based on the turbine instrumentation. This technology is called PEMS: Predictive Emissions Monitoring System. But these technologies do not provide all the information required by the regulator. GRTgaz, the main gas transmission company in France managing 44 turbines spread over 27 stations across France, has decided to monitor its emissions by PEMS for many years. Two years ago, GRTgaz developed successfully its own PEMS equations, organized answers to regulators around this technology and decided to spread the technology across its gas turbine fleet. The complete intellectual path followed is described in the paper GT2014-25242. This 2016 3-part paper describes the PEMS project steps forward. In the first part of the paper, a review is done of the PEMS equations used at GRTgaz for NOx and CO concentrations. The various lean premixed combustion turbines differ in terms of combustion design, control and instrumentation. These differences are analyzed considering their influence on combustion and their impact on the PEMS results accuracy. In order to comply with regulators requirements a calibration of the PEMS results is done every quarter. The results of the first 2 stations equipped with PEMS are described in this first part. The second part of the paper introduces the smoke developed and the neutral air flow to complete the real time calculation required by the regulators: SO2 concentration and the mass flowrates for NOx, CO and SO2. The final calculation integrates the mass flowrate in order to elaborate the total mass emitted into the atmosphere over different time periods. The last part deals with developing personnel involvement, managing the data and compiling the results given to regulators. These aspects were more difficult to implement than expected. The importance of these aspects should not be underestimated because the scientific credibility of PEMS cannot be confirmed without them.

Automated vehicles (AVs)—and the automated driving systems (ADSs) that enable them—are increasing in prevalence but remain far from ubiquitous. Progress has occurred in spurts, followed by lulls, while the motor transportation system learns to design, deploy, and regulate AVs. Automated Vehicles: A Human/Machine Co-learning Experience focuses on how engineers, regulators, and road users are all learning about a technology that has the potential to transform society. Those engaged in the design of ADSs and AVs may find it useful to consider that the spurts and lulls and stakeholder tussles are a normal part of technology transformations; however, this report will provide suggestions for effective stakeholder engagement.

Trailblazing grassroots community advocates from across the United States joined with the Union of Concerned Scientists and Coming Clean to co-develop The Community Guide to Cumulative Impacts: Organizing, Science, and Environmental Policy. Harmful chemicals are typically regulated one at a time. Yet in the real world we are all exposed to multiple harmful chemicals, from the products we use, to pollution sources in our neighborhoods, to legacy pollution in our communities and us. These exposures combine with stressors on health that are often driven by systemic racism and unjust public policies: barriers to healthy food, existing health conditions, and poor access to healthcare. These cumulative impacts add up to harm people, especially in Environmental Justice communities. The Guide will help you take action in your community by providing an overview of strategies, tools, and state and local policies that give regulators more power to deny permits.

The future of food safety assessment in the UK depends on the Food Standards Agency’s (FSA) adaptability and flexibility in responding to and adopting the accelerating developments in science and technology. The Tox21 approach is an example of one recent advancement in the development of alternative toxicity testing approaches and computer modelling strategies for the evaluation of hazard and exposure (New Approach Methodologies (NAMs). A key aspect is the ability to link active concentrations in vitro to likely concentrations in vivo, for which physiologically based pharmacokinetic (PBPK) modelling is ideally suited. The UK FSA and the Committee on Toxicity of Chemicals in Food, Consumer Products, and the Environment (COT) held an “PBPK for Regulators” workshop with multidisciplinary participation, involving delegates from regulatory agencies, government bodies, academics, and industry. The workshop provided a platform to enable expert discussions on the application of PBPK to health risk assessment in a regulatory context. Presentations covered current application of PBPK modelling in the agrochemical industry for in vitro to in vivo extrapolation (IVIVE), pharmaceutical industry for drug absorption related issues (e.g., the effect of food on drug absorption) and drug-drug interaction studies, as well as dose extrapolations to special populations (e.g., those with a specific disease state, paediatric/geriatric age groups, and different ethnicities), environmental chemical risk assessment, an overview of the current regulatory guidance and a PBPK model run-through. This enabled attendees to consider the wide potential and fitness for purpose of the application of PBPK modelling in these fields. Attendees considered applicability in the context of future food safety assessment for refining exposure assessments of chemicals with narrow margins of exposure and/or to fill data gaps from more traditional approaches (i.e., data from animal testing). The overall conclusions from the workshop were as follows: PBPK modelling tools were applicable in the areas of use covered, and that expertise was available (though it is in small numbers). PBPK modelling offers opportunities to address questions for compounds that are otherwise not possible (e.g., considerations of human variability in kinetics) and allows identification of “at risk” subpopulations. The use of PBPK modelling tends to be applied on a case-by-case basis and there appears to be a barrier to widespread acceptance amongst regulatory bodies due to the lack of available in-house expertise (apart from some medical and environmental agencies such as the European Medicines Agency, United States Food and Drug Administration, and the US Environmental Protection Agency, respectively). Familiarisation and further training opportunities on the application of PBPK modelling using real world case studies would help in generating interest and developing more experts in the field, as well as furthering acceptance. In a regulatory context, establishing fitness for purpose for the use of PBPK models requires transparent discussion between regulatory agencies, government bodies, academics, and industry and the development of a harmonised guidance such as by the Organisation for Economic Co-operation and Development (OECD) would provide a starting point. Finally, PBPK modelling is part of the wider “new approach methodologies” for risk assessment, and there should be particular emphasis in modelling both toxicodynamics and toxicokinetics.

This paper presents a comprehensive evaluation of the performance of an interior permanent magnet (IPM) traction motor drive, and analyses the impact of different modulation techniques. The most widely used modulation methods in traction motor drives are Space vector modulation (SVPWM), over-modulation, and six-step modulation have been implemented. A two-dimensional electromagnetic finite element model of the motor is co-simulated with a dynamic model of a field-oriented control (FOC) circuit. For accurate tuning of the current controllers, extended complex vector synchronous frame current regulators are employed. The DC-link voltage utilization, harmonics in the output waveforms, torque ripple, iron losses, and AC copper losses are calculated and compared with sinusoidal excitation. Overall, it is concluded that the selection of modulation technique is related to the operating condition and motor speed, and a smooth transition between different modulation techniques is essential to achieve a better performance.