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Pharmaceutical developers are encouraged to adopt the best practices of being purposefully thoughtful about the use of animals, seeking alternatives wherever possible. They should engage with health authorities to increase their familiarity with the methods, study designs, data outputs, and the context of use for new approach methodologies (NAMs). Although current state of technology does not yet provide adequate models to fully replace in vivo studies, many models are sufficiently good for an augmented approach that will enhance our understanding of in vitro to in vivo correlations and advance the long-term goal of reducing animal use through innovative NAMs. The goal of future nonclinical safety packages is to advance the utilization of such enabling technologies toward appropriate human risk characterization. Establishing confidence in NAMs is a critical first step. For example, sponsors may include both "traditional" and NAM-based nonclinical safety data in regulatory submissions to establish confidence with health authorities. In addition, regulators should create a "safe harbor" for hybrid nonclinical data packages to facilitate iterative learning, refinement, and implementation of NAM-based safety assessment strategies. Sponsors are urged to contribute to NAMs evolution through consortia participation, peer-reviewed publications, and documenting animal reduction in studies/programs, accelerating the eventual elimination of animal use in pharmaceutical development, as envisioned in the FDA Modernization Act 3.0. [ABSTRACT FROM AUTHOR]

Safe Harbor Agreements (SHAs) are one of the voluntary incentive programs designed to neutralize some of the costs and burdens associated with endangered species protection on private lands under the Endangered Species Act. They have demonstrated mixed success in terms of landowner participation, indicating that merely offering an SHA is not enough to persuade landowners to enter into agreements with government entities to protect endangered species. Yet little research has investigated landowner decision‐making and the programmatic structures that influence participation in SHAs. In this study, we employed hypothetical choice experiment offerings of Houston toad (Bufo houstonensis) SHAs to explore the reasoning behind Texas landowners' (n = 956) willingness to participate in the program, and to reveal programmatic characteristics most appealing to landowners. Respondents were most frequently willing to enroll in an SHA because of beliefs about and a sense of responsibility towards conserving nature, and were unwilling to potentially enroll in an SHA because they did not know enough about SHAs, did not want the government involved in their land management, and did not want to enter a binding agreement regarding endangered species. Additionally, respondents were more likely to enroll in hypothetical SHAs if the agreements included 10‐year contract durations and full future assurances, and less likely to enroll if they included 30‐year contract durations. This study provides program administrators with insights into how to improve the design and delivery of SHAs to increase participation among private landowners. [ABSTRACT FROM AUTHOR]

The democratization of technology to re-create content and make that content publicly available has spurred a wave of user-generated content (UGC), which has produced remarkable social and economic benefits. However, under current copyright law, UGC creators face the dilemma of being deterred from creating UGC because of the risk of copyright infringement, copyright owners can rarely obtain remuneration from UGC, and UGC platforms profit from UGC without being held liable for copyright infringement. Recent proposals to extend fair use and compulsory licenses to UGC creators and impose direct liability on UGC platforms cannot solve the UGC dilemma due to the inadequate or unreasonable regulation of UGC platforms. This study aims to solve the UGC dilemma by proposing a non-exploitative UGC levy on UGC platforms. We demonstrate the necessity of the non-exploitative UGC levy by conducting a comparative study of existing proposals and illustrate the feasibility of the non-exploitative UGC levy through an institutional analysis of its framework and enforcement mechanisms. Justification of the proposed levy and responses to possible criticism are also provided. The levy scheme also provides inspiration for how copyright law can address burgeoning artificial intelligence-generated content (AIGC). [ABSTRACT FROM AUTHOR]

This Article examines the often-overlooked practice of "selective performance" of standard form consumer contracts--where sellers permit employees to exercise discretion by waiving or modifying contractual terms to maintain customer satisfaction. While such flexibility can benefit consumers, it raises serious concerns about discrimination. Through both theoretical analysis and empirical evidence, this Article demonstrates that discretionary performance can disproportionately favor certain consumer groups, particularly along racial and gender lines, leading to biased and inequitable outcomes. Drawing on examples from diverse sectors, including retail, insurance, and mortgage services, the Article highlights how marginalized communities, especially Black consumers, frequently face harsher treatment and greater obstacles in the enforcement of contractual rights. In response, the Article proposes actionable strategies to mitigate bias in the performance of consumer contracts. These strategies include debiasing training, the implementation of more objective decision-making criteria, increased monitoring and accountability, diversifying personnel, and leveraging artificial intelligence to detect and prevent discriminatory patterns. Additionally, the Article explores how regulators can incentivize sellers to adopt these bias-reducing measures through a "safe harbor" framework. By integrating insights from psychology and institutional design, this Article offers a roadmap for promoting fairness and reducing discrimination in the performance of consumer contracts, ultimately advocating for a more equitable marketplace. [ABSTRACT FROM AUTHOR]

On 13 April 2021, a mesoscale convective system (MCS) swept across the southeastern Louisiana coast, capsizing the 39-m Seacor Power roughly 7 km from shore and leaving 13 mariners drowned or missing. In addition to the severe straight-line winds that sank the vessel, sustained surface winds > 20 m s−1 behind the leading convection persisted well after the main convective band, inhibiting search and rescue efforts. Though complete historical fatality statistics are unavailable, the 13 deaths associated with this event likely represent one of the deadliest severe convective weather events in modern U.S. maritime history. This analysis integrates in situ, remotely sensed, and reanalysis datasets to reconstruct the 2021 Seacor Power accident as well as ascertain its depiction in day-of operational convection-allowing model (CAM) guidance. Results suggest that the MCS formed along an unanalyzed coastal boundary and developed a strong mesohigh to the east of the wreck as it moved offshore. The resulting zonally oriented pressure gradient directed stiff easterly winds over the wreck for several hours, even as the squall line had propagated well away from the coast. This multihour period of severe weather along the Louisiana coast was relatively well resolved by morning-of CAM guidance, providing optimism that future such events may be anticipated with the lead times required by vulnerable seacraft to reach safe harbor. Future severe convective weather watches containing marine zones might include a "marine" section detailing the potential sea conditions, analogous to the "aviation" section in current severe weather watches. [ABSTRACT FROM AUTHOR]

In the early 2000s, the EU adopted the Electronic Commerce Directive to regulate information society service providers. An important part of this piece of legislation was the safe harbor provisions, which exempted intermediary service providers from liability for illegal content transmitted or hosted by their users, provided that they complied with specific conditions. After more than twenty years, the emergence of significant online platforms and the increased use of those services has resulted in new risks and challenges for individuals, companies, and society as a whole, which led the European Union to adopt a new regulatory framework for intermediary services. The Digital Services Act retains the liability exemption regime of the Electronic Commerce Directive but introduces new transparency and due diligence obligations for intermediary services, especially for online platforms. The new regulatory framework is expected to substantially impact globally, as it applies to all intermediary service providers offering services within the EU, regardless of their location. This study explores the main features of the DSA and their potential effects on the future development of the Internet. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Social Sciences Institute / Sosyal Bilimler Enstitüsü Dergisi is the property of Bingol University / Rectorate and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Genomic Safe Harbors (GSH) are loci used for the insertion of exogenous genetic elements, enabling exogenous gene expressing predictably without alterations of the host genome. These sites are becoming increasingly important as the gene editing technologies advance rapidly. Currently, only a few GSHs have been identified in the pig genome. In this study, a novel strategy was demonstrated for the efficient insertion of exogenous genetic material into the third exon of the UTY gene on the Y chromosome using CRISPR/Cas9-mediated homology arm-mediated end joining. The safety of the locus was verified according to the proper expression of the inserted EGFP gene without altering the expression of UTY. This approach enables the integration and expression of the exogenous gene at this locus, indicating that the UTY locus serves as a genomic safe harbor site for gene editing in the pig genome. Located on the Y chromosome, this site can be utilized for sex-biased pig breeding and developing biomedical models. [ABSTRACT FROM AUTHOR]

Background: The recent rise of large language models has triggered renewed interest in medical free text data, which holds critical information about patients and diseases. However, medical free text is also highly sensitive. Therefore, de-identification is typically required but is complicated since medical free text is mostly unstructured. With the Masketeer algorithm, we present an effective tool to de-identify German medical text. Methods: We used an ensemble of different masking classes to remove references to identifiable data from over 35,000 clinical notes in accordance with the HIPAA Safe Harbor Guidelines. To retain additional context for readers, we implemented an entity recognition scheme and corpus-wide pseudonymization. Results: The algorithm performed with a sensitivity of 0.943 and specificity of 0.933. Further performance analyses showed linear runtime complexity (O(n)) with both increasing text length and corpus size. Conclusions: In the future, large language models will likely be able to de-identify medical free text more effectively and thoroughly than handcrafted rules. However, such gold-standard de-identification tools based on large language models are yet to emerge. In the current absence of such, we hope to provide best practices for a robust rule-based algorithm designed with expert domain knowledge. [ABSTRACT FROM AUTHOR]

Standard zebrafish transgenesis involves random transgene integration with resource-intensive screening. While phiC31 integrase-based attP/attB recombination has streamlined transgenesis in mice and Drosophila, validated attP-based landing sites for universal applications are lacking in zebrafish. Here, we developed phiC31 Integrase Genomic Loci Engineered for Transgenesis (pIGLET) as transgenesis approach, with two attP landing sites pIGLET14a and pIGLET24b from well-validated Tol2 transgenes. Both sites facilitate diverse transgenesis applications including reporters and Cre/loxP transgenes. The pIGLET14a and pIGLET24b landing sites consistently yield 25 to 50% germline transmission, substantially reducing the resources needed for transgenic line generation. Transgenesis into these sites enables reproducible expression patterns in F0 zebrafish embryos for enhancer discovery and testing of gene regulatory variants. Together, our new landing sites streamline targeted, reproducible zebrafish transgenesis as a robust platform for various applications while minimizing the workload for generating transgenic lines. [ABSTRACT FROM AUTHOR]

Since the widespread adoption of the Uniform Commercial Code (UCC) in the 1960s, the UCC's name-based filing system has been a constant embarrassment to its drafters. System overhauls in 1998 and 2010 failed to fix it. In Florida, the problem came to a head in 1944 Beach Boulevard, LLC u. Live Oak Banking. Based on a widely shared misunderstanding of how Florida's unorthodox, privatized UCC filing system worked, the Florida Supreme Court held that the system had no search logic, so the UCC § 9-506(c) safe harbor from debtor name errors did not apply. Instead, a "zerotolerance" test applied, with the consequence that any error in a debtor's name on a financing statement "no matter how minor" renders the financing statement ineffective and the secured party unperfected. This Article presents the first formal empirical study estimating an error rate for UCC filings anywhere in the United States. The study found that under the Florida Supreme Court's zero-tolerance test, 32% of UCC filings in Florida against registered organizations-over 230,000 filings-are ineffective by reason of name errors alone. Even if Florida had adopted the traditional search logic used in other states and qualified for the safe harbor, 5% of the filings-about 11,650 filings-would still have been ineffective for name errors alone. This Article argues that, with respect to filings against registered organizations, the states should replace the UCC's name-based filing system with a point-and-click filing system. In a point-and-click system, UCC filings against registered organizations would be made, stored, and searched in the state's entity records. Such a system is already operational in the United Kingdom. Instead of filers and searchers trying to reproduce the elusive "public organic record" names of registered organizations in the correct boxes on filing and search requests, filers and searchers would need only to navigate to the debtor's entity record on the state's website. There, lenders could click on their debtors' correct names to file financing statements, and searchers could see all UCC filings against their debtors in one place. All information a filer or searcher would need to determine whether it was filing or searching against the correct entity would be visible to it on the same page. That would include addresses, public organic records, and annual reports. Point-and-click would eliminate debtor name errors in filing and searching, eliminate the need for debtor name amendments and debtor name monitoring, greatly simplify the processes of filing and searching, and dramatically reduce wrong-entity and wrong-state filing errors. It would increase the accuracy of the UCC filing system while cutting its costs to filers, searchers, and the state to a fraction of their current levels. [ABSTRACT FROM AUTHOR]

Individuals chronically infected with hepatitis B virus (HBV) and hepatitis Delta virus (HDV) present an increased risk of developing cirrhosis and hepatocellular carcinoma in comparison to HBV mono-infected individuals. Although HDV only replicates in individuals coinfected or superinfected with HBV, there is currently no in vitro model that can stably express both viruses simultaneously, mimicking the chronic infections seen in HBV/HDV patients. Here, we present the HepG2BD cell line as a novel in vitro culture system for long-term replication of HBV and HDV. HepG2BD cells derive from HepG2.2.15 cells in which a 2 kb HDV cDNA sequence was inserted into the adeno-associated virus safe harbor integration site 1 (AAVS1) using CRISPR-Cas9. A Tet-Off promoter was placed 5′ of the genomic HDV sequence for reliable initiation/repression of viral replication and secretion. HBV and HDV replication were then thoroughly characterized. Of note, non-dividing cells adopt a hepatocyte-like morphology associated with an increased production of both HDV and HBV virions. Finally, HDV seems to negatively interfere with HBV in this model system. Altogether, HepG2BD cells will be instrumental to evaluate, in vitro, the fundamental HBV–HDV interplay during simultaneous chronic replication as well as for antivirals screening targeting both viruses. [ABSTRACT FROM AUTHOR]

American consumer credit regulation is in the midst of a doctrinal revolution. Usury laws, for centuries the mainstay of consumer credit regulation, have been repealed, preempted, or otherwise undermined. At the same time, changes in the structure of the consumer credit marketplace have weakened the traditional alignment of lender and borrower interests. As a result, lenders cannot be relied upon to avoid making excessively risky loans out of their own self-interest. Two new doctrinal approaches have emerged piecemeal to fill the regulatory gap created by the erosion of usury laws and lenders' self-interested restraint: a revived unconscionability doctrine and ability-to-repay requirements. Some courts have held loan contracts unconscionable based on excessive price terms, even if the loan does not violate the applicable usury law. Separately, for many types of credit products, lenders are now required to evaluate the borrower's repayment capacity and to lend only within such capacity. The nature of these ability-to-repay requirements varies considerably, however, by product and jurisdiction. This Article terms these doctrinal developments collectively as the "New Usury." The New Usury represents a shift from traditional usury law's bright-line rules to fuzzier standards like unconscionability and ability-to-repay. Although there are benefits to this approach, it has developed in a fragmented and haphazard manner. Drawing on the lessons from the New Usury, this Article calls for a more comprehensive and coherent approach to consumer credit price regulation through a federal ability-to-repay requirement for all consumer credit products coupled with product-specific regulatory safe harbors, a combination that offers the best balance of functional consumer protection and business certainty. [ABSTRACT FROM AUTHOR]

We examine the joint effects of litigation risk and regulation in shaping firms' financial reporting decisions. Specifically, we investigate how these disciplining mechanisms influence firms' disclosure of non‐GAAP earnings metrics, which have been at the forefront of the SEC's regulatory concerns in recent years. We employ a plausibly exogenous shock to litigation risk based on a US circuit court ruling to explore how litigation risk influences firms' non‐GAAP earnings disclosures. We find a robust negative relation between litigation risk and both the likelihood and aggressiveness of non‐GAAP reporting. However, we find a significant attenuation in the sensitivity of non‐GAAP disclosure to litigation risk after the implementation of Regulation G (Reg G), despite evidence that aggressive non‐GAAP reporting persists in the post‐Reg G environment. Additional analyses indicate that this attenuation is actually the net result of two unique effects. First, we find that Reg G created a de facto "safe harbor" for non‐GAAP reporting among firms in circuits with higher litigation risk and a "curtailment effect" among firms in the circuit with the lowest litigation risk. Overall, Reg G led to a convergence in non‐GAAP reporting practices irrespective of firms' circuit‐specific litigation risk. We posit that this net attenuation of litigation risk's influence on non‐GAAP reporting is likely an unintended consequence of Reg G. [ABSTRACT FROM AUTHOR]

This rejoinder acknowledges the thoughtful commentary of Tushnet (2023) on Wlömert et al. (2023) and summarizes the study's relevance for questions concerning platform regulation. Tushnet [Tushnet R (2023) Comment on "Frontiers: The interplay of user-generated content, content industry revenues, and platform regulation: Quasi-experimental evidence from YouTube". Marketing Sci. 43(1):13–15] provides a commentary on Wlömert et al. [Wlömert N, Papies D, Clement M, Spann M (2023) Frontiers: The interplay of user-generated content, content industry revenues, and platform regulation: Quasi-experimental evidence from YouTube. Marketing Sci. 43(1):1–12], who analyzed the quasi-experiment that occurred when numerous songs became available as user-generated content (UGC) on YouTube, following an agreement between YouTube and the German collecting society GEMA. Tushnet's thoughtful commentary centers around the scope of legal protection that UGC platforms enjoy, and whether the situation examined in Wlömert et al. qualifies as a "legal safe harbor." In our rejoinder, we clarify the study's relevance for questions concerning platform regulation, highlight the implications of these regulatory aspects for platforms' strong bargaining power, as reflected in comparatively low payouts to rightsholders, and discuss how the sampling versus cannibalization effects that we study impact market outcomes for different stakeholders under these market conditions. History: Olivier Toubia served as the senior editor. [ABSTRACT FROM AUTHOR]

A large quasi-experiment in Germany shows that user generated video streaming helps the niche but hurts big artists total music industry revenues. An ongoing debate among firms, rightsholders, particularly in the music industry, and policymakers in the United States and the European Union concerns potential changes to the regulation of user-generated content (UGC) video streaming platforms (e.g., YouTube). Currently, safe harbor provisions protect platforms from liability for copyright-infringing content uploaded by users, and requirements for compensating rightsholders for UGC are weak, resulting in comparatively low payouts. At the same time, it is unclear how a change in these regulations would affect consumer demand for this content on other platforms with higher payouts (e.g., Spotify), that is, whether UGC platforms stimulate or displace demand on other platforms. We study a quasi-experiment that occurred when numerous songs became available as UGC on YouTube after an agreement between YouTube and the German royalty collecting society. Our analysis of an unprecedented data set covering 600,000 songs by 38,000 artists reveals an intriguing finding: Although UGC availability stimulates demand in other streaming channels for most songs, cannibalization occurs for recent releases and hit releases, turning the overall revenue effect negative. We discuss how policymakers can use these findings to understand the implications of changes in regulation, and how labels and artists can decide which content to block or allow on UGC platforms. History: Olivier Toubia served as the senior editor. This paper was accepted through the Marketing Science: Frontiers review process. Supplemental Material: The data and online appendices are available at https://doi.org/10.1287/mksc.2022.0080. [ABSTRACT FROM AUTHOR]

Patents incentivize the disclosure of novel technology by granting the inventor the right to exclude others from the production, use, import, or sale of their invention for a limited time. When considered in the context of medical devices and pharmaceutical drug therapies, patent exclusivity implicates patient and societal health and wellness. Amidst the rise in drug prices, the Drug Price Competition and Patent Term Restoration Act of 1984, commonly referred to as the Hatch-Waxman Act, addressed the seemingly competing interests of incentivizing medical innovation through patent protection and lowering consumer drug prices by increasing access to generic drug products. Congress bridged this divide, in part, by establishing a new statutory scheme aimed at resolving two unintended distortions in an invention's patent term. The Hatch-Waxman Act altered the patent law landscape by providing the first legislative exemption to patent infringement, known as the "Safe Harbor." Generally, for the Safe Harbor infringement exemption to shield an otherwise infringing activity, the "patented invention" must be used for specific purposes of creating information required under a federal law regulating the manufacture, use, or sale of drugs. But what are the types of "patented inventions" that Congress envisioned? Did Congress intend the scope of Safe Harbor's "patented invention" clause to exclusively encompass inventions subject to regulatory approvals, like drugs, or did the clause encompass a broader, more general collection of patented research technology, like a fluorescent tagged antibody? This note argues that the term "patent invention" should be interpreted broadly, to include research tools that are not themselves subject to federal regulatory approval. First, principles of statutory interpretation support the plain reading of the Safe Harbor provision to include research tools and weigh against reading unfounded restrictions into the provision's terms. Second, endorsement of this broad interpretation is checked by the Safe Harbor's additional requirement that the unauthorized use of the "patented invention" be solely for uses reasonably related to the creation of information required under federal law regulating drugs. And, ultimately, public policy favors lowering drug prices by increasing the number of competitive drugs in the marketplace, which would be facilitated by opening research tools to the statutory protections afforded by the Safe Harbor. [ABSTRACT FROM AUTHOR]

The Internal Revenue Service issued Notice 2024-2 on December 20, 2023. It is a grab bag of guidance for certain provisions of the SECURE 2.0 Act of 2022. The guidance covers many of the SECURE 2.0 Act provisions, but omits some of the complex items, such as the mandatory flip from 401(k) plan deferrals to Roth deferrals for highly compensated employees beginning in 2026 and the optional student loan matching contribution provision. Following a user-friendly Q&A format, the guidance includes clarifications regarding the 2025 required automatic enrollment provisions, de minimis incentives for employee plan contributions, optional treatment of employer contributions as Roth contributions, optional terminal illness distributions, safe harbor corrections of certain deferral failures, and extended deadlines for formal amendments adopting provisions of the SECURE 2.0 Act of 2022 and other prior legislation. [ABSTRACT FROM AUTHOR]

Innovations in fnancial technology have enabled nonbank frms to market, originate, and service consumer loans entirely online via web-based lending platforms. These online lenders promote themselves as a faster, disintermediated alternative to traditional lending that leverages technology to provide borrowers with convenient and near-instantaneous access to a wider variety of credit products. Yet despite its claimed advantages, the online lending industry remains perpetually entangled in litigation and controversy surrounding its prevailing business model. Most prominently, lawmakers, regulators, and courts are sharply divided as to whether online lending platforms should be able to escape otherwise applicable state usury laws by "partnering" with chartered depository institutions to originate high-interest loans. Experts also question the (mis)alignment of incentives between parties at each stage of the lending process, particularly given that the online lender performs a traditionally bank-like role in the transaction but typically bears no economic interest in the loans it originates. In response, this Note argues that a recent settlement between Colorado authorities and two online lenders offers a uniquely practicable template for resolving these interrelated challenges by applying pressure to the incentive mechanisms that lead online lenders to originate high-risk--and therefore high-interest--loans that state usury laws would ordinarily prohibit. [ABSTRACT FROM AUTHOR]

Gene integration at site-specific loci is a critical approach for understanding the function of a gene in cells or animals. The AAVS1 locus is a well-known safe harbor for human and mouse studies. In this study, we found an AAVS1-like sequence (pAAVS1) in the porcine genome using the Genome Browser and designed TALEN and CRISPR/Cas9 to target the pAAVS1. The efficiency of CRISPR/Cas9 in porcine cells was superior to that of TALEN. We added a loxP-lox2272 sequences to the pAAVS1 targeting donor vector containing GFP for further exchange of various transgenes via recombinase-mediated cassette exchange (RMCE). The donor vector and CRISPR/Cas9 components were transfected into porcine fibroblasts. Targeted cells of CRISPR/Cas9-mediated homologous recombination were identified by antibiotic selection. Gene knock-in was confirmed by PCR. To induce RMCE, another donor vector containing the loxP-lox2272 and inducible Cre recombinase was cloned. The Cre-donor vector was transfected into the pAAVS1 targeted cell line, and RMCE was induced by adding doxycycline to the culture medium. RMCE in porcine fibroblasts was confirmed using PCR. In conclusion, gene targeting at the pAAVS1 and RMCE in porcine fibroblasts was successful. This technology will be useful for future porcine transgenesis studies and the generation of stable transgenic pigs. [ABSTRACT FROM AUTHOR]

Innovations in financial technology have enabled nonbank firms to market, originate, and service consumer loans entirely online via web-based lending platforms. These online lenders promote themselves as a faster, disintermediated alternative to traditional lending that leverages technology to provide borrowers with convenient and near-instantaneous access to a wider variety of credit products. Yet despite its claimed advantages, the online lending industry remains perpetually entangled in litigation and controversy surrounding its prevailing business model. Most prominently, lawmakers, regulators, and courts are sharply divided as to whether online lending platforms should be able to escape otherwise applicable state usury laws by "partnering" with chartered depository institu-tions to originate high-interest loans. Experts also question the (mis)alignment of incentives between parties at each stage of the lending process, particularly given that the online lender performs a traditionally bank-like role in the transaction but typically bears no economic interest in the loans it originates. In response, this Note argues that a recent settlement between Colorado authorities and two online lenders offers a uniquely practicable template for resolving these interrelated challenges by applying pressure to the incentive mechanisms that lead online lenders to originate high-risk--and therefore high-interest--loans that state usury laws would ordinarily prohibit. [ABSTRACT FROM AUTHOR]

A recent article in the journal "Science" highlights a potential breakthrough in gene therapy, where a little-known gene editor called ARCUS was used to restore a missing liver enzyme in an infant with a severe metabolic disorder. The therapy aims to integrate the curative gene into a "safe harbor" location in the genome to avoid disrupting existing DNA and triggering cancer. While the success of this approach is promising, some researchers caution about potential long-term risks, such as liver cancer, associated with gene-insertion strategies. Despite the risks, experts believe that the safe harbor approach is a valuable advancement in treating devastating diseases like urea cycle disorders. [Extracted from the article]

This article analyzes the importance of supply-side fluctuations for corporate hedging. To establish a causal link, we exploit a regulatory change that allows derivatives counterparties to circumvent the Bankruptcy Code's automatic stay: the Safe Harbor Reform of 2005. Following the reform-induced expansion in the availability of derivatives, fuel hedging by airlines nearing financial distress (those that benefited most from the reform) significantly increased in comparison with financially sound airlines. We find that the hedging propensity similarly increased in a general sample of nonfinancial firms. In line with theory, we also find that operating performance increased for the affected firms. [ABSTRACT FROM AUTHOR]

According to the Pension Rights Center only 54 percent of all civilian workers participated in a workplace retirement plan. Further, the median account balance for all workers was only $15,000. Congress, cognizant of the need to increase participation in workplace plans, eased the rules for multiple-employer plans, enhanced plan safe harbor opportunities, and made other improvements. [ABSTRACT FROM AUTHOR]

An online marketplace operator that incorporates its own and third-party sellers' offers uses an identical sign to an EU trademark in the goods offered by third-party sellers without the proprietor's consent if a well-informed and reasonably observant internet user establishes a link between the services of that operator and the sign, and, in particular, when the user may form the impression that the operator itself is marketing, in its own name and on its own account, the goods bearing that sign. [ABSTRACT FROM AUTHOR]

Narrow parity clauses seem to be exempt under the new Vertical BER. The European Commission apparently considers narrow parity clauses typically to fulfill the exemption requirements under Art. 101(3) TFEU, at least below the marketshare threshold. This contrasts with the decision of the German Federal Supreme Court (BGH) in Booking.com, in which the BGH decided that narrow best price clauses have “manifest restrictive effects on competition“ and do not – at least not typically – fulfil the exemption requirements under Art. 101(3) TFEU. This article concludes that the block exemption of narrow parity clauses is incompatible with Art. 101(3) AEUV and therefore null and void. Undertakings using narrow parity clauses do not benefit from the safe harbor. [ABSTRACT FROM AUTHOR]

In recent years, generative artificial intelligence (AI) has become a major technological innovation that has attracted global attention due to its revolutionary efficiency, triggering a new wave of technological revolution. Companies from all over the world are actively engaged in research and development of generative AI models, such as OpenAI’s ChatGPT, Google’s Bard, and Chinese companies such as Baidu’s Wenxin Yiyan and iFlytek’s SparkDesk Large Language Model. At the same time, legislative activities targeting generative AI have also begun, such as the European Union’s proposed Artificial Intelligence Act, and related regulatory white papers and blue papers have been released by the United States and the United Kingdom. Therefore, from the perspective of international competitiveness, it is also necessary for China to quickly improve its legal regulations for artificial intelligence and promote industry development. While generative AI brings about an efficiency revolution, the content it generates also poses risks to national security, public safety, and private rights. China has already established existing laws and drafted departmental regulations specifically to regulate the risks of AI-generated content. However, there are still shortcomings in terms of disclosure of AI-generated content, content responsibility, and complaint mechanisms. From an improvement perspective, disclosure should have two sets of systems: explicit disclosure and implicit disclosure, where service providers are responsible for implicit disclosure obligations, and users are responsible for explicit disclosure obligations. In terms of content responsibility, the binary division of content providers and technical service providers is no longer applicable to the scenario of AI-generated content. Service providers should not be simply classified as content providers, as this will impose a heavy burden on service providers and be detrimental to the healthy development of the industry. A safe harbor mechanism that adapts to the characteristics of generative AI should be explored on the basis of reference to the safe harbor rules, and this mechanism should be compatible with the user’s content responsibility. In terms of complaint mechanisms, it is not reasonable to require service providers to take targeted blocking measures based on user complaints. Two schemes can be considered to improve this: one is to decouple complaints from targeted blocking measures as stipulated in the previous departmental regulations, and the other is to significantly raise the threshold for taking targeted blocking measures in response to complaints. Finally, when formulating policies for regulating the risks of generative AI content, the issue of the industry’s international competitiveness should be considered, and a regulatory path that classifies risks themselves should be adopted to achieve the dual objectives of promoting the healthy development of the industry and preventing risks. Existing academic papers on the regulation of generative AI mainly study it from the perspective of overall risk regulations, while this article explores it from the perspective of content risk regulation, and there are very few similar studies. In terms of research perspective, the innovation of this article mainly lies in: first, it clearly proposes that existing safe harbor rules should not apply to generative AI service providers, and new content responsibility“safe harbors”should be created for them. Second, the classification of risks has shifted from different products to different risks generated by the same product. For high-risk illegal and harmful content such as national security and public safety risks, service providers have a heavier obligation to take blocking measures, while for lower-risk illegal and harmful content such as infringement of private rights, service providers have a relatively lighter obligation to take blocking measures. [ABSTRACT FROM AUTHOR]

Using the records of hundreds of thousands of court cases filed across the United States between 2010 and 2016, we assess whether residence in public housing reduces the risk of facing an eviction filing. Comparing with similar sets of private market renters, we demonstrate that those living in public housing face equal risk. Once filed against, public housing residents face a far higher risk of serial eviction filing. Within states, public and private market serial eviction filing rates are strongly correlated—evidence that public housing property managers respond to local eviction policies in ways that resemble their private market counterparts. We report on in-depth interviews with property managers from two housing authorities in Ohio. Property managers use the courts to facilitate rent collection in jurisdictions that enable the practice, but doing so does not necessarily result in better outcomes on evaluations conducted by the Department of Housing and Urban Development. [ABSTRACT FROM AUTHOR]

Efficient and stable expression of foreign genes in cells and transgenic animals is important for gain-of-function studies and the establishment of bioreactors. Safe harbor loci in the animal genome enable consistent overexpression of foreign genes, without side effects. However, relatively few safe harbor loci are available in pigs, a fact which has impeded the development of multi-transgenic pig research. We report a strategy for efficient transgene knock-in in the endogenous collagen type I alpha 1 chain (COL1A1) gene using the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system. After the knock-in of a 2A peptide-green fluorescence protein (2A-GFP) transgene in the last codon of COL1A1 in multiple porcine cells, including porcine kidney epithelial (PK15), porcine embryonic fibroblast (PEF) and porcine intestinal epithelial (IPI-2I) cells, quantitative PCR (qPCR), Western blotting, RNA-seq and CCK8 assay were performed to assess the safety of COL1A1 locus. The qPCR results showed that the GFP knock-in had no effect (P=0.29, P=0.66 and P=0.20 for PK15, PEF and IPI-2I cells, respectively) on the mRNA expression of COL1A1 gene. Similarly, no significant differences (P=0.64, P=0.48 and P=0.80 for PK15, PEF and IPI-2I cells, respectively) were found between the GFP knock-in and wild type cells by Western blotting. RNA-seq results revealed that the transcriptome of GFP knock-in PEF cells had a significant positive correlation (P

This article explores the ongoing debate among lawyers regarding the use of arbitration as a method for resolving disputes between lawyers and clients. Supporters of arbitration argue that it is a faster, more cost-effective, and confidential alternative to litigation. However, critics point out that arbitration may not always be the quickest or most economical option and lacks appellate review. The article provides guidance to lawyers who wish to include arbitration clauses in their engagement agreements and enforce them against resistant clients. It also discusses the varying requirements for binding arbitration clauses and the additional obligations imposed by state ethics committees. The article examines the views of courts and ethics committees on arbitration of fee disputes, legal malpractice claims, and ethical complaints. It concludes by outlining six key considerations that lawyers must address to ensure the enforceability of their arbitration agreements. The article emphasizes the importance of providing clients with sufficient information to make informed decisions about arbitration and ensuring that the terms of the agreement are fair and reasonable. It also highlights the need for clear and straightforward language in arbitration clauses and the potential for clients to argue waiver of arbitration based on litigation conduct or unnecessary delay. [Extracted from the article]

This article discusses a recent memorandum opinion by the Tax Court in ES NPA Holding LLC v. Commissioner, which clarifies the application of the profits interest safe harbor to tiered partnership structures. The court ruled that the taxpayer's receipt of a profits interest in a lower-tier partnership qualified as a non-taxable event under the safe harbor provided in Revenue Procedure 93-27. The court's decision provides guidance on the use of such structures and settles certain previously unsettled tax issues. However, it should be noted that the court's analysis was limited to the facts and arguments specific to this case and may not apply to all tiered partnership structures. The decision is expected to be cited by practitioners to support the application of the profits interest safe harbor in similar situations involving tiered partnership structures. [ABSTRACT FROM AUTHOR]

Background: One of the most prominent questions in the field of transgenesis is 'Where in the genome to integrate a transgene?'. Escape from epigenetic silencing and promoter shutdown of the transgene needs reliable genomic safe harbor (GSH) loci. Advances in genome engineering technologies combined with multi-omics bioinformatics data have enabled rational evaluation of GSH loci in the host genome. Currently, no validated GSH loci have been evaluated in the chicken genome. Results: Here, we analyzed and experimentally examined two GSH loci in the genome of chicken cells. To this end, putative GSH loci including chicken HIPP-like (cHIPP; between DRG1 and EIF4ENIF1 genes) and chicken ROSA-like (cROSA; upstream of the THUMPD3 gene) were predicted using multi-omics bioinformatics data. Then, the durable expression of the transgene was validated by experimental characterization of continuously-cultured isogenous cell clones harboring DsRed2-ΔCMV-EGFP cassette in the predicted loci. The weakened form of the CMV promoter (ΔCMV) allowed the precise evaluation of GSH loci in a locus-dependent manner compared to the full-length CMV promoter. Conclusions: cHIPP and cROSA loci introduced in this study can be reliably exploited for consistent bio-manufacturing of recombinant proteins in the genetically-engineered chickens. Also, results showed that the genomic context dictates the expression of transgene controlled by ΔCMV in GSH loci. [ABSTRACT FROM AUTHOR]

This paper re-examines the impact of the EU Market Abuse Directive (MAD) on the market reaction around share repurchase announcements. We use a unique hand-collected dataset of firms listed on the Athens Stock Exchange, and we find evidence that contrasts with previous conclusions for large European economies. The implementation of the MAD is followed by a significant increase in announcement abnormal returns, which is more pronounced in initial repurchase programs. Our results remain robust to a series of robustness tests. We attribute our findings to cross-country differences in institutional framework and pre-MAD existing national laws. Collectively, our results support the notion that EU directives do not have a uniform effect across Member States. Thus, the impact of such reforms should also be examined in individual capital market studies. [ABSTRACT FROM AUTHOR]

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The paper provides useful information about music consumption, but not about legal safe harbors, whose effects it cannot test because they did not change between periods. This useful article about the effects of music on YouTube on consumption of the same music elsewhere should be understood for what it is: An empirical investigation of YouTube's effects. It allows no conclusions about "safe harbors" both because YouTube was not relying on the safe harbor regime either before or after the relevant policy change and because, as YouTube's lack of reliance shows, the safe harbor regime primarily protects thousands of websites that don't behave like YouTube. Under the European Union's new Article 17, sites like YouTube are now required to negotiate with copyright owners to license works uploaded by users who do not own the copyright thereto. YouTube, however, was already doing this. The article [Wlömert N, Papies D, Clement M, Spann M (2023) Frontiers: The interplay of user-generated content, content industry revenues, and platform regulation: Quasi-experimental evidence from YouTube. Marketing Sci. 43(1):1–12] has implications for what music companies should ask for in these negotiations. However, it would be a mistake to generalize from YouTube to the Internet as a whole. History: Olivier Toubia served as the senior editor. [ABSTRACT FROM AUTHOR]