The Rise of State-Specific Attempts to Decipher the Sufficiency-of-a-Debtor-Name Standard Under Revised Article 9 and the End of Uniformity in Secured Transactions

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Extreme Policy Makeover: Re-Evaluating Current U.S.-Vietnam Relations under the International Religious Freedom Act

Following the signing of the Paris Peace Accord in 1973, the relationship between the United States and Vietnam remained essentially frozen. In 2000, the signing of the United States-Vietnam Bilateral Trade Agreement was an epic step in the normalization of relations. In addition, the BTA was hailed as a means of effectuating positive change in the area of Vietnam\u27s human rights. Unfortunately, the state of religious freedom in Vietnam has deteriorated while economic ties with the United States have strengthened. Despite Vietnam\u27s purported respect for religious freedom, violations continue. Vietnam restricts the practice of religion, detains religious leaders, and tolerates forced renunciations of faith by local officials. These acts violate the International Covenant on Civil and Political Rights, to which Vietnam has acceded. Vietnam\u27s violations of the right to religious freedom have also drawn the concern of the international community. Specifically, the United States has called for improvements in Vietnam\u27s religious rights record, utilizing diplomatic mean coupled with continued engagement in the hopes that Vietnam will voluntarily enact changes. However, this approach has failed to yield concrete progress. In 2004, the U.S. Department of State designated Vietnam a Country of Particular Concern as provided in the International Religious Freedom Act. Because the IRFA mandates affirmative action against violators of religious freedom, the United States must abandon constructive engagement in Vietnam. Instead, the IRFA provides the framework for opposing violations under the responsible engagement doctrine. In doing so, the United States may employ economic pressure to narrowly target violators, while allowing the liberalizing effect of engagement to continue where it does not sustain violations. By fully implementing the IRFA in accordance with the tenets of responsible engagement, the United States would actively oppose violations rather than engaging Vietnam with the hope that improvements will occur. Moreover, this extreme makeover of current policy would balance the dual interests of improved religious freedom and bilateral relations

Blockchain Stock Ledgers

American corporate law contains a seemingly innocuous mandate. Corporations must maintain appropriate books and records, including a stock ledger with the corporation\u27s shareholders and stock ownership. The importance of accurate stock ownership records is obvious. Corporations must know who owns each of its outstanding shares at any point in time. Among other things, this allows corporations to determine who receives dividends and who is entitled to vote. In theory, keeping accurate records of stock ownership should be a simple matter. But despite diligent efforts, serious share discrepancies plague corporations, and reconciliation is often functionally impossible. Doing so may require the examination of records from millions of trades, including records from hundreds of participant brokers and custodial banks (not to mention records from their individual clients). So, when disputes arise, there is frequently no easy answer. This Article charts the use of blockchain technology as a potential solution to the systemic issues hindering efforts to maintain accurate records of stock transactions. In doing so, this Article accomplishes three goals. First, it establishes that federal efforts to resolve the paperwork crisis of the 1970\u27s created a concomitant problem the lack of reliable records of stock ownership, which now threatens the exercise of shareholder rights. Second, it demonstrates that practical constraints, not legal barriers, stand as the most significant impediment to the application of blockchain technology to corporate recordkeeping and global capital markets. Third, it argues that despite reasons for skepticism, states should proactively amend corporate codes to authorize the use of blockchain technology because it enables corporate choice and facilitates efforts by private actors to assess the viability of innovative solutions. This Article concludes by drawing transferable lessons to improve law and policy as new applications of blockchain technology continue to emerge

Rethinking Virtual Currency Regulation in the Bitcoin Age

This Article investigates an increasingly important yet under-developed body of law: regulation of virtual currency. At its peak in March of 2014, the daily volume of Bitcoin transactions in United States dollars exceeded $575,000,000. The growing mainstream acceptance of Bitcoin, however, is best illustrated by the growing number of leading merchants that have decided to accept Bitcoin payments. While Bitcoin’s rise as an alternative payment method is well-chronicled, Bitcoin’s impact extends further due to its use as an investment vehicle and its ability to spur the growth of an industry of Bitcoin-based businesses. Despite increasingly widespread use, Bitcoin (and other virtual currencies) have largely operated without the burden of regulation. Why? Like the potentially transformative innovations that preceded Bitcoin, virtual currency raises unique challenges for which existing legal models may be unprepared. As policymakers struggle to catch-up, the effort to develop an appropriate regulatory regime for virtual currency is at a critical juncture. The response in the United States has thus far involved regulatory bodies acting independently to clarify the treatment of virtual currency under a variety of different laws designed to regulate traditional payment systems, financial services, and investments. This Article argues, contrary to this approach, that a narrow focus on the technical application and extension of existing law creates a deficient regulatory regime. Instead, we suggest that policymakers should: (1) engage the various agency stakeholders to promote cross-communication; (2) think more globally about the wide spectrum of issues arising from virtual currency; and (3) embrace the unique and distinct characteristics of virtual currency. In support of this proposition, we show that refocusing on the collection of policy goals advanced by existing law offers policymakers an additional tool to aid in the development of a comprehensive, cohesive, and appropriately-scaled virtual currency regulatory model

miR-21 Plays a Dual Role in Tumor Formation and Cytotoxic Response in Breast Tumors

Breast cancer (BrCa) relies on specific microRNAs to drive disease progression. Oncogenic miR-21 is upregulated in many cancers, including BrCa, and is associated with poor survival and treatment resistance. We sought to determine the role of miR-21 in BrCa tumor initiation, progression and treatment response. In a triple-negative BrCa model, radiation exposure increased miR-21 in both primary tumor and metastases. In vitro, miR-21 knockdown decreased survival in all BrCa subtypes in the presence of radiation. The role of miR-21 in BrCa initiation was evaluated by implanting wild-type miR-21 BrCa cells into genetically engineered mouse models where miR-21 was intact, heterozygous or globally ablated. Tumors were unable to grow in the mammary fat pads of miR-21−/− mice, and grew in ~50% of miR-21+/− and 100% in miR-21+/+ mice. The contribution of miR-21 to progression and metastases was tested by crossing miR-21−/− mice with mice that spontaneously develop BrCa. The global ablation of miR-21 significantly decreased the tumorigenesis and metastases of BrCa, while sensitizing tumors to radio-and chemotherapeutic agents via Fas/FasL-dependent apoptosis. Therefore, targeting miR-21 alone or in combination with various radio or cytotoxic therapies may represent novel and efficacious therapeutic modalities for the future treatment of BrCa patients

An Intermittent Live Cell Imaging Screen for siRNA Enhancers and Suppressors of a Kinesin-5 Inhibitor

Kinesin-5 (also known as Eg5, KSP and Kif11) is required for assembly of a bipolar mitotic spindle. Small molecule inhibitors of Kinesin-5, developed as potential anti-cancer drugs, arrest cell in mitosis and promote apoptosis of cancer cells. We performed a genome-wide siRNA screen for enhancers and suppressors of a Kinesin-5 inhibitor in human cells to elucidate cellular responses, and thus identify factors that might predict drug sensitivity in cancers. Because the drug's actions play out over several days, we developed an intermittent imaging screen. Live HeLa cells expressing GFP-tagged histone H2B were imaged at 0, 24 and 48 hours after drug addition, and images were analyzed using open-source software that incorporates machine learning. This screen effectively identified siRNAs that caused increased mitotic arrest at low drug concentrations (enhancers), and vice versa (suppressors), and we report siRNAs that caused both effects. We then classified the effect of siRNAs for 15 genes where 3 or 4 out of 4 siRNA oligos tested were suppressors as assessed by time lapse imaging, and by testing for suppression of mitotic arrest in taxol and nocodazole. This identified 4 phenotypic classes of drug suppressors, which included known and novel genes. Our methodology should be applicable to other screens, and the suppressor and enhancer genes we identified may open new lines of research into mitosis and checkpoint biology

The conservation status of the world's freshwater molluscs

With the biodiversity crisis continuing unchecked, we need to establish levels and drivers of extinction risk, and reassessments over time, to effectively allocate conservation resources and track progress towards global conservation targets. Given that threat appears particularly high in freshwaters, we assessed the extinction risk of 1428 randomly selected freshwater molluscs using the IUCN Red List Categories and Criteria, as part of the Sampled Red List Index project. We show that close to one-third of species in our sample are estimated to be threatened with extinction, with highest levels of threat in the Nearctic, Palearctic and Australasia and among gastropods. Threat levels were higher in lotic than lentic systems. Pollution (chemical and physical) and the modification of natural systems (e.g. through damming and water abstraction) were the most frequently reported threats to freshwater molluscs, with some regional variation. Given that we found little spatial congruence between species richness patterns of freshwater molluscs and other freshwater taxa, apart from crayfish, new additional conservation priority areas emerged from our study. We discuss the implications of our findings for freshwater mollusc conservation, the adequacy of a sampled approach and important next steps to estimate trends in freshwater mollusc extinction risk over time

Clonal Hematopoiesis and Risk of Prostate Cancer in Large Samples of European Ancestry Men

Little is known regarding the potential relationship between clonal hematopoiesis (CH) of indeterminate potential (CHIP), which is the expansion of hematopoietic stem cells with somatic mutations, and risk of prostate cancer, the fifth leading cause of cancer death of men worldwide. We evaluated the association of age-related CHIP with overall and aggressive prostate cancer risk in two large whole-exome sequencing studies of 75 047 European ancestry men, including 7663 prostate cancer cases, 2770 of which had aggressive disease, and 3266 men carrying CHIP variants. We found that CHIP, defined by over 50 CHIP genes individually and in aggregate, was not significantly associated with overall (aggregate HR = 0.93, 95% CI = 0.76-1.13, P = 0.46) or aggressive (aggregate OR = 1.14, 95% CI = 0.92-1.41, P = 0.22) prostate cancer risk. CHIP was weakly associated with genetic risk of overall prostate cancer, measured using a polygenic risk score (OR = 1.05 per unit increase, 95% CI = 1.01-1.10, P = 0.01). CHIP was not significantly associated with carrying pathogenic/likely pathogenic/deleterious variants in DNA repair genes, which have previously been found to be associated with aggressive prostate cancer. While findings from this study suggest that CHIP is likely not a risk factor for prostate cancer, it will be important to investigate other types of CH in association with prostate cancer risk

An electrochromic ionic liquid: design, characterisation and performance in a solid state platform

This work describes the synthesis and characteristics of a novel electrochromic ionic liquid (IL) based on a phosphonium core tethered to a viologen moiety. When integrated into a solid-state electrochromic platform, the viologen modified IL behaved as both the electrolyte and the electrochromic material. Platform fabrication was achieved through in situ photo-polymerisation and encapsulation of this novel IL within a hybrid sol-gel. Important parameters of the platform performance, including its coloration efficiency, switching kinetics and optical properties were characterised using UV/Vis spectroscopy and cyclic voltammetry in tandem. The electrochromic platform exhibits a coloration efficiency of 10.72 cm2C-1, and a varied optical output as a function of the incident current. Despite the rather viscous nature of the material, the platform exhibited approximately two orders of magnitude faster switching kinetics (221 seconds to reach 95 % absorbance) when compared to previously reported electrochromic ILs (18,000 seconds)

Roles for the Conserved Spc105p/Kre28p Complex in Kinetochore-Microtubule Binding and the Spindle Assembly Checkpoint

Kinetochores attach sister chromatids to microtubules of the mitotic spindle and orchestrate chromosome disjunction at anaphase. Although S. cerevisiae has the simplest known kinetochores, they nonetheless contain approximately 70 subunits that assemble on centromeric DNA in a hierarchical manner. Developing an accurate picture of the DNA-binding, linker and microtubule-binding layers of kinetochores, including the functions of individual proteins in these layers, is a key challenge in the field of yeast chromosome segregation. Moreover, comparison of orthologous proteins in yeast and humans promises to extend insight obtained from the study of simple fungal kinetochores to complex animal cell kinetochores.We show that S. cerevisiae Spc105p forms a heterotrimeric complex with Kre28p, the likely orthologue of the metazoan kinetochore protein Zwint-1. Through systematic analysis of interdependencies among kinetochore complexes, focused on Spc105p/Kre28p, we develop a comprehensive picture of the assembly hierarchy of budding yeast kinetochores. We find Spc105p/Kre28p to comprise the third linker complex that, along with the Ndc80 and MIND linker complexes, is responsible for bridging between centromeric heterochromatin and kinetochore MAPs and motors. Like the Ndc80 complex, Spc105p/Kre28p is also essential for kinetochore binding by components of the spindle assembly checkpoint. Moreover, these functions are conserved in human cells.Spc105p/Kre28p is the last of the core linker complexes to be analyzed in yeast and we show it to be required for kinetochore binding by a discrete subset of kMAPs (Bim1p, Bik1p, Slk19p) and motors (Cin8p, Kar3p), all of which are nonessential. Strikingly, dissociation of these proteins from kinetochores prevents bipolar attachment, even though the Ndc80 and DASH complexes, the two best-studied kMAPs, are still present. The failure of Spc105 deficient kinetochores to bind correctly to spindle microtubules and to recruit checkpoint proteins in yeast and human cells explains the observed severity of missegregation phenotypes