Despite impressive advances in the treatment of HIV/AIDS over the past 30 years, there is much we do not understand about the HIV life-cycle. While it is well-known that HIV and related primate lentiviruses induce an aberrant DNA damage response (DDR) in infected cells, it remains unclear exactly how or why this occurs. Working from a curated list of 40 human genes associated with DDR, bearing markers of positive selection, and induced by interferon gamma signaling, we performed a CRISPR screen for genes that increased or decreased infectivity upon knockout in primary CD4+ T cells. The results were analyzed by one-sample T-test to identify putative susceptibility and antiviral genes. Subsequently, preliminary experiments were conducted to verify the results of the screen via overexpression and shRNA silencing experiments. This study has identified ESPL1, PALB2, and RBBP8 as potential susceptibility factors, and POLG, MUTYH, and BRIP1 as potential antiviral factors.
This Article analyzes the role of Latin American international economic law scholarship within the global economic order. Many of the problems that Latin Americans face today relate to the global economy, such as labor conditions, access to medicine, and the use of natural resources, among others. The discussion of these problems, however, seldom recognizes the role of international economic law scholarship. Although the knowledge created by this scholarship may not completely explain why States actively behave in a certain way, it can serve to explain why they may refrain from certain actions. This Article argues that scholarship on international economic law plays a crucial role in the creation and reproduction of the current global economic order. If this claim is correct, regional scholarship can do more for Latin America than serving the advisory and litigation needs of States. By recognizing its role in constituting the global economic order, international economic law scholarship can promote alternative theories and practices that may help Latin America and its people find their place in the global economy.
Groundwater management is important and challenging, and nowhere is this more evident than in California. Managed aquifer recharge (MAR) projects can play an important role in ensuring California manages its groundwater sustainably. Although the benefits and economic costs of surface water storage have been researched extensively, the benefits and economic costs of MAR have been little researched. Historical groundwater data are sparse or proprietary within the state, often impairing groundwater analyses. General obligation bonds from ballot propositions offer a strategic means of mining information about MAR projects, because the information is available publicly. We used bond-funding applications to identify anticipated MAR project benefits and proposed economic costs. We then compared these costs with actual project costs collected from a survey, and identified factors that promote or limit MAR. Our analysis indicates that the median proposed economic cost for MAR projects in California is $410 per acre-foot per year ($0.33 per cubic meter per year). Increasing Water Supply, Conjunctive Use, and Flood Protection are the most common benefits reported. Additionally, the survey indicates that (1) there are many reported reasons for differences between proposed and actual costs ($US 2015) and (2) there is one primary reason for differences between proposed recharge volumes and actual recharge volumes (AFY): availability of source water for recharge. Although there are differences between proposed and actual costs per recharge volume ($US 2015/AFY), the ranges for proposed costs per recharge volume and actual costs per recharge volume for the projects surveyed generally agree. The two most important contributions to the success of a MAR project are financial support and good communication with stakeholders.
When litigants entered Southern courtrooms after the end of the Civil War, they encountered a tangled morass of unexpected legal questions related to the end of slavery. Though the need to face such problems was ubiquitous across the former slaveholding republic, each state contended with such matters uniquely, producing a series of different solutions to the same fundamental problems. Principal among them: Why were there so many legacies of slavery contested in court? How should the law treat slavery and former slaves after the supposed end of the peculiar institution? In what ways did litigants themselves help to shape the meaning of freedom? How complete was the abolition of slavery if the institution itself remained open to ongoing litigation?
State courts and individual petitioners were forced to confront the altered legal terrain of the post-Civil War South and negotiate the precise meanings of the Thirteenth Amendment, the end of slavery, the transformation of the former slave states, and ultimately, the reunification of the United States. Evaluating the many responses to these issues exposes legal Reconstruction’s many possibilities; some would become the road not taken, while others set the standard for managing slavery’s remaining legal quandaries. In some courtrooms, jurists were committed to a total eradication of slavery and the laws that had once supported it, revealing Reconstruction’s fleeting potential to secure true freedom for four million former slaves. The outcomes of other cases reveal judges clinging to assumptions about race, law, and Southern society that reflected the antebellum past. As this dissertation shows, the more conservative route ultimately became the prevailing legal paradigm, but it took nearly ten years to arrive at this conclusion, challenging the notion that there was ever a fixed meaning or moment of emancipation.
As the consequences of liberal opioid prescribing have become apparent, efforts to address the role of the health care system in supporting more balanced opioid use and the prevention and treatment of opioid use disorder have increased. Developing a unified and multidisciplinary approach can lead to an integrated care model that emphasizes primary prevention, harm reduction, and transition to life-sustaining treatment while also maintaining attentiveness to effective pain management. A model for this, which follows the nomenclature in proscribing antimicrobial use, is the development of an opioid stewardship program. Such programs allow for the integration of diverse perspectives and new mandates and uses a patient-centered approach with an iterative evaluation process. We describe a group of adoptable efforts that have been utilized successfully at our institutions and may be adapted and optimized to the needs and resources of other hospitals and health care systems.
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