Paradigm For Regulation Research Articles

Current constraints to reconcile tropical forest restoration and bioeconomy

AbstractLarge-scale forest restoration is vital for delivering a broad array of ecosystem services benefits to society. However, it is often perceived as an economically noncompetitive land use choice. Integrating economic opportunities into restoration aligns socioeconomic and environmental goals, reducing conflicts between forest production and conservation-oriented management decisions. Supply chains focusing on high-value goods can enhance the reach of forest restoration efforts and unite ecological and economic benefits in a multifunctional manner. The bioeconomy has emerged as a potential but critical driver for attracting investments in restoration. We outline the challenges and solutions to reconcile forest restoration and bioeconomy, specifically about (i) native timber production, (ii) non-timber forest products, (iii) biotechnological products, and (iv) intangible ecosystem services. This requires collaborative and multidisciplinary efforts to improve investment in large-scale projects. The intricacies of these issues intersect with research development, market dynamics, legal frameworks, and regulatory paradigms, underscoring the necessity for nuanced and tailored public policy interventions. These integrated approaches should enable tropical countries to lead the global forest-based economy and usher in a new era of forest restoration. Graphical abstract

Going Dutch? Comparing Regulatory and Contracting Policy Paradigms via Amsterdam and London SPAC Experiences

AbstractThe special purpose acquisition company (SPAC) is a cash shell listed with the sole purpose of acquiring an operating business. Although SPACs, in a high interest rate environment, may have recently fallen out of favor, it was not long ago when they dominated the US markets. SPACs did not, though, come without controversy. Arguably, the incentives ingrained in typical SPACs make them poor investments for long-term shareholders, while lucrative for their sponsors and shareholders seeking to exit prior to an acquisition. Europe was not immune to the SPAC craze, but London and Amsterdam took differing approaches. While London employs a regulatory paradigm pursuant to which SPACs (to avoid a trading suspension upon announcement of an acquisition) must adopt specific terms, Amsterdam follows a contracting paradigm, giving market participants broad scope to implement any SPAC terms that they see fit. In this article, the terms of the cohort of London- and Amsterdam-listed SPACs from 2021 and 2022 are comprehensively scrutinized in the context of the terms that are embedded in the typical US SPAC. This article finds that many of the terms mandated by London’s regulatory rules are also found in Amsterdam-listed SPACs. However, many of those London- and Amsterdam-listed SPACs also display many of the qualities seen in the US which have caused so much consternation. Taking inspiration from the phrase ‘going Dutch’, it is argued that an optimal SPAC policy that assuages concerns levied at US SPACs should take contributions from both the regulatory and contracting paradigms.

Cell Mediated Reactions Create TGF-β Delivery Limitations in Engineered Cartilage

During native cartilage development, endogenous TGF-β activity is tightly regulated by cell-mediated chemical reactions in the extracellular milieu (e.g., matrix and receptor binding), providing spatiotemporal control in a manner that is localized and short acting. These regulatory paradigms appear to be at odds with TGF-β delivery needs in tissue engineering (TE) where administered TGF-β is required to transport long distances or reside in tissues for extended durations. In this study, we perform a novel examination of the influence of cell-mediated reactions on the spatiotemporal distribution of administered TGF-β in cartilage TE applications. Reaction rates of TGF-β binding to cell-deposited ECM and TGF-β internalization by cell receptors are experimentally characterized in bovine chondrocyte-seeded tissue constructs. TGF-β binding to the construct ECM exhibits non-linear Brunauer–Emmett–Teller (BET) adsorption behavior, indicating that as many as seven TGF-β molecules can aggregate at a binding site. Cell-mediated TGF-β internalization rates exhibit a biphasic trend, following a Michaelis-Menten relation (Vmax=2.4 molecules cell-1 s-1, Km=1.7 ng mL-1) at low ligand doses (≤130ng/mL), but exhibit an unanticipated non-saturating power trend at higher doses (≥130ng/mL). Computational models are developed to illustrate the influence of these reactions on TGF-β spatiotemporal delivery profiles for conventional TGF-β administration platforms. For TGF-β delivery via supplementation in culture medium, these reactions give rise to pronounced steady state TGF-β spatial gradients; TGF-β concentration decays by ∼90% at a depth of only 500 μm from the media-exposed surface. For TGF-β delivery via heparin-conjugated affinity scaffolds, cell mediated internalization reactions significantly reduce the TGF-β scaffold retention time (160 to 360-fold reduction) relative to acellular heparin scaffolds. This work establishes the significant limitations that cell-mediated chemical reactions engender for TGF-β delivery and highlights the need for novel delivery platforms that account for these reactions to achieve optimal TGF-β exposure profiles. Statement of SignificanceDuring native cartilage development, endogenous TGF-β activity is tightly regulated by cell-mediated chemical reactions in the extracellular milieu (e.g., matrix and receptor binding), providing spatiotemporal control in a manner that is localized and short acting. However, the effect of these reactions on the delivery of exogenous TGF-β to engineered cartilage tissues remains not well understood. In this study, we demonstrate that cell-mediated reactions significantly restrict the delivery of TGF-β to cells in engineered cartilage tissue constructs. For delivery via media supplementation, reactions significantly limit TGF-β penetration into constructs. For delivery via scaffold loading, reactions significantly limit TGF-β residence time in constructs. Overall, these results illustrate the impact of cell-mediated chemical reaction on TGF-β delivery profiles and support the importance of accounting for these reactions when designing TGF-β delivery platforms for promoting cartilage regeneration.

Giant and robust thermal nonreciprocity in a fluid–solid multiphase circulator

Nonreciprocal heat transfer is crucial for modern energy utilization and conversion. Rotational bias in circulators made of fluid or solid monophase materials enables thermal nonreciprocity at two output ports. However, sensitivity to multiple factors like port position and circulator radius necessitates precise rotational bias, making giant thermal nonreciprocity fragile. Here, we propose a fluid–solid multiphase circulator by incorporating a solid rotating ring into a fluid circulator. The rotation speed flexibly controls the heat exchange ratio between the fluid–solid interface. Giant thermal nonreciprocity is obtained when the solid and fluid speeds are nearly synchronized, yielding distinctly different temperature amplitudes at two output ports. The rectification ratio robustly reaches the maximum due to its independence of port position and circulator radius. These findings also apply to more ports and other diffusion domains like mass transport, inspiring a fluid–solid hybrid paradigm for diffusion regulation.

Preferred Distance in Human-Drone Interaction.

In two augmented-reality experiments, we transferred the paradigm of interpersonal distance regulation to human-drone interaction. In the first experiment, we used a simple spherical drone model and explored how both hovering height and approach angle affect the preferred distance. Drone height above the ground had a strong effect. The preferred distance to the drone was larger than that typically found toward human actors, in particular, when the drone trajectory was very high. In the second experiment, we sought to gain a deeper understanding of the factors that may influence this effect. In addition to the simple spherical drone model used in the first experiment, we also varied its appearance and attachment to the ground. Surprisingly, anthropomorphic features increased preferred distances. We, therefore, discuss the extent to which social aspects and subjectively perceived danger influence the preferred distance for interaction with drones, which thus need to be considered in the design of human-drone interaction.

Перспективы применения критерия de minimis в делах о картелях

This article presents an analysis of the phenomenon of cartels in the paradigm of antimonopoly legal regulation. The author examines domestic and foreign judicial practice on the application of the de minimis criterion in cartel cases and assesses the prospects for its use.

A developmental gradient reveals biosynthetic pathways to eukaryotic toxins in monocot geophytes

Numerous eukaryotic toxins that accumulate in geophytic plants are valuable in the clinic, yet their biosynthetic pathways have remained elusive. A notable example is the >150 Amaryllidaceae alkaloids (AmAs), including galantamine, an FDA-approved treatment for Alzheimer's disease. We show that while AmAs accumulate to high levels in many daffodil tissues, biosynthesis is localized to nascent, growing tissue at the leaf base. A similar trend is found in the production of steroidal alkaloids (e.g., cyclopamine) in corn lily. This model of active biosynthesis enabled the elucidation of a complete set of biosynthetic genes that can be used to produce AmAs. Taken together, our work sheds light on the developmental and enzymatic logic of diverse alkaloid biosynthesis in daffodils. More broadly, it suggests a paradigm for biosynthesis regulation in monocot geophytes, where plants are protected from herbivory through active charging of newly formed cells with eukaryotic toxins that persist as above-ground tissue develops.

MiR-31-mediated local translation at the mitotic spindle is important for early development.

miR-31 is a highly conserved microRNA that plays crucial roles in cell proliferation, migration and differentiation. We discovered that miR-31 and some of its validated targets are enriched on the mitotic spindle of the dividing sea urchin embryo and mammalian cells. Using the sea urchin embryo, we found that miR-31 inhibition led to developmental delay correlated with increased cytoskeletal and chromosomal defects. We identified miR-31 to directly suppress several actin remodeling transcripts, including β-actin, Gelsolin, Rab35 and Fascin. De novo translation of Fascin occurs at the mitotic spindle of sea urchin embryos and mammalian cells. Importantly, miR-31 inhibition leads to a significant a increase of newly translated Fascin at the spindle of dividing sea urchin embryos. Forced ectopic localization of Fascin transcripts to the cell membrane and translation led to significant developmental and chromosomal segregation defects, highlighting the importance of the regulation of local translation by miR-31 at the mitotic spindle to ensure proper cell division. Furthermore, miR-31-mediated post-transcriptional regulation at the mitotic spindle may be an evolutionarily conserved regulatory paradigm of mitosis.

Crystallographically textured zinc nucleation and planar electrodeposition for zinc metal batteries via magnetoelectric and magnetization effects

The premature failure of zinc metal anodes is critically associated with the uncontrollable nucleation and random orientation of hexagonal Zn electrodeposits. Herein, we realize to control the crystallographical texture of zinc crystal nuclei and enable planar electrodeposition by simply applying a magnetic field. We unveil the novel mechanism of magnetoelectric and magnetization effects on the different deposition behavior under magnetic fields. The magnetohydrodynamic effect can flatten the uneven electrode surface during electrodeposition by deflecting the motion of Zn2+ ions. Especially, influences of the Hall effect on electrode polarization and magnetization effect on crystallographical Zn nucleation are first uncovered and validated. We demonstrate the proper use of these magnetic field-related effects is propitious to dense, homogeneous, and highly reversible deposition/dissolution of Zn metal anodes. The cycle lives of Zn anodes are extended 2–4 times at different currents and cycling capacities. Moreover, exceptional reversibility of 99.85 % is achieved. Full cells with a low N/P ratio of 5.4 and ultrahigh cathode mass loading of 19.98 mg cm−2 can release stable capacity up to 3.2 mAh cm−2. Our study provides new paradigms for magnetic field regulation of Zn metal battery electrochemistry, as well as for other external field applications in adjusting battery performance.

The Transformative Impact of Financial Technology (FinTech) on Regulatory Compliance in the Banking Sector

Financial Technology (FinTech) has emerged as a disruptive force in the banking sector, revolutionizing the way financial services are delivered and consumed. This review explores the transformative impact of FinTech on regulatory compliance within the banking industry. The integration of advanced technologies such as artificial intelligence, blockchain, and big data analytics has enabled financial institutions to enhance operational efficiency, improve customer experience, and expand market reach. However, these innovations have also posed unprecedented challenges to traditional regulatory frameworks designed to safeguard financial stability and consumer protection. This review examines how FinTech innovations have necessitated regulatory adaptation and evolution. It highlights the complexities introduced by novel financial products, digital payment systems, and decentralized finance (DeFi) platforms, which often operate beyond conventional regulatory boundaries. Regulatory compliance in areas such as anti-money laundering (AML), know your customer (KYC) requirements, and data privacy has become more intricate as FinTech solutions blur geographical and jurisdictional lines. Moreover, the strategies employed by regulatory bodies and financial institutions to address these challenges effectively. These include leveraging regulatory technology (RegTech) solutions for enhanced monitoring and compliance automation, fostering collaboration between regulators and industry stakeholders, and advocating for agile regulatory frameworks capable of accommodating rapid technological advancements. Looking ahead, the review anticipates ongoing shifts in regulatory paradigms to accommodate the transformative impact of FinTech. It emphasizes the importance of proactive regulatory approaches that balance innovation with risk management, ensuring the integrity and resilience of the banking sector amidst a rapidly evolving digital landscape. This provides a comprehensive overview of how FinTech is reshaping regulatory compliance in banking. It underscores the need for adaptive regulatory strategies and collaborative efforts to harness the full potential of FinTech while safeguarding financial stability and consumer trust.

Global regulation via modulation of ribosome pausing by the ABC-F protein EttA

Having multiple rounds of translation of the same mRNA creates dynamic complexities along with opportunities for regulation related to ribosome pausing and stalling at specific sequences. Yet, mechanisms controlling these critical processes and the principles guiding their evolution remain poorly understood. Through genetic, genomic, physiological, and biochemical approaches, we demonstrate that regulating ribosome pausing at specific amino acid sequences can produce ~2-fold changes in protein expression levels which strongly influence cell growth and therefore evolutionary fitness. We demonstrate, both in vivo and in vitro, that the ABC-F protein EttA directly controls the translation of mRNAs coding for a subset of enzymes in the tricarboxylic acid (TCA) cycle and its glyoxylate shunt, which modulates growth in some chemical environments. EttA also modulates expression of specific proteins involved in metabolically related physiological and stress-response pathways. These regulatory activities are mediated by EttA rescuing ribosomes paused at specific patterns of negatively charged residues within the first 30 amino acids of nascent proteins. We thus establish a unique global regulatory paradigm based on sequence-specific modulation of translational pausing.

Ammonia transporter RhBG initiates downstream signaling and functional responses by activating NFκB

Transceptors, solute transporters that facilitate intracellular entry of molecules and also initiate intracellular signaling events, have been primarily studied in lower-order species. Ammonia, a cytotoxic endogenous metabolite, is converted to urea in hepatocytes for urinary excretion in mammals. During hyperammonemia, when hepatic metabolism is impaired, nonureagenic ammonia disposal occurs primarily in skeletal muscle. Increased ammonia uptake in skeletal muscle is mediated by a membrane-bound, 12 transmembrane domain solute transporter, Rhesus blood group-associated B glycoprotein (RhBG). We show that in addition to its transport function, RhBG interacts with myeloid differentiation primary response-88 (MyD88) to initiate an intracellular signaling cascade that culminates in activation of NFκB. We also show that ammonia-induced MyD88 signaling is independent of the canonical toll-like receptor-initiated mechanism of MyD88-dependent NFκB activation. In silico, in vitro, and in situ experiments show that the conserved cytosolic J-domain of the RhBG protein interacts with the Toll-interleukin-1 receptor (TIR) domain of MyD88. In skeletal muscle from human patients, human-induced pluripotent stem cell-derived myotubes, and myobundles show an interaction of RhBG-MyD88 during hyperammonemia. Using complementary experimental and multiomics analyses in murine myotubes and mice with muscle-specific RhBG or MyD88 deletion, we show that the RhBG-MyD88 interaction is essential for the activation of NFkB but not ammonia transport. Our studies show a paradigm of substrate-dependent regulation of transceptor function with the potential for modulation of cellular responses in mammalian systems by decoupling transport and signaling functions of transceptors.

Addressing chemically-induced obesogenic metabolic disruption: selection of chemicals for in vitro human PPARα, PPARγ transactivation, and adipogenesis test methods.

Whilst western diet and sedentary lifestyles heavily contribute to the global obesity epidemic, it is likely that chemical exposure may also contribute. A substantial body of literature implicates a variety of suspected environmental chemicals in metabolic disruption and obesogenic mechanisms. Chemically induced obesogenic metabolic disruption is not yet considered in regulatory testing paradigms or regulations, but this is an internationally recognised human health regulatory development need. An early step in the development of relevant regulatory test methods is to derive appropriate minimum chemical selection lists for the target endpoint and its key mechanisms, such that the test method can be suitably optimised and validated. Independently collated and reviewed reference and proficiency chemicals relevant for the regulatory chemical universe that they are intended to serve, assist regulatory test method development and validation, particularly in relation to the OECD Test Guidelines Programme. To address obesogenic mechanisms and modes of action for chemical hazard assessment, key initiating mechanisms include molecular-level Peroxisome Proliferator-Activated Receptor (PPAR) α and γ agonism and the tissue/organ-level key event of perturbation of the adipogenesis process that may lead to excess white adipose tissue. Here we present a critical literature review, analysis and evaluation of chemicals suitable for the development, optimisation and validation of human PPARα and PPARγ agonism and human white adipose tissue adipogenesis test methods. The chemical lists have been derived with consideration of essential criteria needed for understanding the strengths and limitations of the test methods. With a weight of evidence approach, this has been combined with practical and applied aspects required for the integration and combination of relevant candidate test methods into test batteries, as part of an Integrated Approach to Testing and Assessment for metabolic disruption. The proposed proficiency and reference chemical list includes a long list of negatives and positives (20 chemicals for PPARα, 21 for PPARγ, and 11 for adipogenesis) from which a (pre-)validation proficiency chemicals list has been derived.

Physiological Roles of an Acinetobacter-specific σ Factor.

The Gram-negative pathogen Acinetobacter baumannii is considered an "urgent threat" to human health due to its propensity to become antibiotic resistant. Understanding the distinct regulatory paradigms used by A. baumannii to mitigate cellular stresses may uncover new therapeutic targets. Many γ-proteobacteria use the extracytoplasmic function (ECF) σ factor, RpoE, to invoke envelope homeostasis networks in response to stress. Acinetobacter species contain the poorly characterized ECF "SigAb;" however, it is unclear if SigAb has the same physiological role as RpoE. Here, we show that SigAb is a metal stress-responsive ECF that appears unique to Acinetobacter species and distinct from RpoE. We combine promoter mutagenesis, motif scanning, and ChIP-seq to define the direct SigAb regulon, which consists of sigAb itself, the stringent response mediator, relA, and the uncharacterized small RNA, "sabS." However, RNA-seq of strains overexpressing SigAb revealed a large, indirect regulon containing hundreds of genes. Metal resistance genes are key elements of the indirect regulon, as CRISPRi knockdown of sigAb or sabS resulted in increased copper sensitivity and excess copper induced SigAb-dependent transcription. Further, we found that two uncharacterized genes in the sigAb operon, "aabA" and "aabB", have anti-SigAb activity. Finally, employing a targeted Tn-seq approach that uses CRISPR-associated transposons, we show that sigAb, aabA, and aabB are important for fitness even during optimal growth conditions. Our work reveals new physiological roles for SigAb and SabS, provides a novel approach for assessing gene fitness, and highlights the distinct regulatory architecture of A. baumannii.

CDKL3 is a targetable regulator of cell cycle progression in cancers.

Cell cycle regulation is largely abnormal in cancers. Molecular understanding and therapeutic targeting of the aberrant cell cycle are essential. Here, we identified that an underappreciated serine/threonine kinase, cyclin-dependent kinase-like 3 (CDKL3), crucially drives rapid cell cycle progression and cell growth in cancers. With regard to mechanism, CDKL3 localizes in the nucleus and associates with specific cyclin to directly phosphorylate retinoblastoma (Rb) for quiescence exit. In parallel, CDKL3 prevents the ubiquitin-proteasomal degradation of cyclin-dependent kinase 4 (CDK4) by direct phosphorylation on T172 to sustain G1 phase advancement. The crucial function of CDKL3 in cancers was demonstrated both in vitro and in vivo. We also designed, synthesized, and characterized a first-in-class CDKL3-specific inhibitor, HZ1. HZ1 exhibits greater potency than CDK4/6 inhibitor in pan-cancer treatment by causing cell cycle arrest and overcomes acquired resistance to CDK4/6 inhibitor. In particular, CDKL3 has significant clinical relevance in colon cancer, and the effectiveness of HZ1 was demonstrated by murine and patient-derived cancer models. Collectively, this work presents an integrated paradigm of cancer cell cycle regulation and suggests CDKL3 targeting as a feasible approach in cancer treatment.

Regulation in the age of calamity: Changing the regulatory paradigm.

Regulation in the age of calamity: Changing the regulatory paradigm.

Relevance of EIA in Sustainable Development with Labour Law

The process of drafting legislation that concerns the livelihood of many people needs to be a careful and participatory process, the Job Creation Bill has crucial problems when viewed from the methodological aspects, paradigm and substance of regulation in the policy field of over-regulated and over-lapping issues that occur in the regulation of fields related to development and investment will not be resolved because the Job Creation Bill requires around 500 derivative regulations so that it has the potential to create a complex hyper-regulated. Realising that there is a need to create a conducive investment climate to realise development, it should not ignore the principle of sustainable development. The purpose of this research was to find out the relevance of EIA in sustainable development in Indonesia where the problem with the current job creation law is suspected of changing the function of EIA which was previously one of the licensing requirements to something whose function is no longer important or only needs to increase the problem with the concept of regulation regarding the environment which was previously regulated by Law Number 32 of 2009 concerning Environmental Protection and Management (UPPLH) using a licensing-based approach. This research used normative or doctrinal research methods.

A Review of the MFS Regulatory Framework to Control IFF in Bangladesh

Mobile financial services (MFS), with their focus on technology and ease of use, have emerged as a novel approach for developing countries to address the problem of adopting best practices to promote financial inclusivity. However, if there are no effective regulations or guidelines in place on a national and international level, the purpose of achieving full financial inclusion and the Sustainable Development Goals might go in vain. For instance, to prevent illicit financial flow (IFF) and ensure that this financial system operates properly, the central bank of Bangladesh, one of the world’s fastest-developing nations, implemented the most recent MFS rule. However, a number of MFS-related fraud incidents have prompted scholars to critically assess the Bangladesh Bank’s (BB) MFS regulatory system with a focus on the efficiency of IFF prevention. This study has demonstrated that the current regulatory system has a weak KYC verification system using a comparative methodology. Following that, if someone has access to someone’s personal information, they also have access to their MFS accounts. In general, the current MFS adheres to a risk-based regulatory paradigm that forces regulators to wait until a hazard occurs and limits them to this legal framework. Policy makers would then be advised by this study to implement a smart regulatory approach in order to establish a climate that is anti-IFF.

Social Determinants of Health as a Dimension of State Policy: A Comparative Analysis

This article explores the extensive international regulatory frameworks governing the healthcare sector, with a primary focus on developed nations worldwide, encompassing the United States, France, Germany, and the United Kingdom. The authors offer insights into various national healthcare systems, contending that the regulatory paradigms within this industry are inextricably linked to the socio-economic policies specific to each country. Modern healthcare systems are deemed "advantageous" due to the emergence of mixed healthcare structures and diverse organizational forms, undergoing constant reform across the globe. The authors underscore the imperative need for effectively institutionalizing the healthcare sector. While acknowledging the inherent imperfections within the various healthcare organizational models mentioned, the article posits that a judiciously structured healthcare paradigm uniquely possesses the capacity to augment both the quality and accessibility of healthcare—a pivotal determinant for the amelioration of overall quality of life and citizen well-being.

A Review on various aspects of Regulatory Affairs

In order to guarantee the efficacy, safety, and calibre of medications, medical equipment, and other healthcare supplies, Regulatory Affairs is essential. Anticipating future trends and difficulties in Regulatory Affairs is crucial as the healthcare sector changes due to technological breakthroughs, globalization, and new regulatory paradigms. This abstract examines the consequences of developing fields for regulatory frameworks, including gene treatments, digital health, artificial intelligence, and personalized medicine. It also covers the increased significance of real-world evidence, patient-centric approaches, and international harmonization in regulatory decision-making. In addition, it looks at the difficulties presented by supply chain interruptions, cybersecurity risks, and regulatory divergence in a world that is changing quickly. Stakeholders may effectively navigate the complicated regulatory landscape of the future by embracing innovation, collaboration, and adaptive regulatory methods facilitate the timely delivery of safe and effective healthcare products to patients worldwide.