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Novel Oxindoles as Potent Anti-HIV Agents

合成化学 2004年第Z1期12卷 8-8页

作者： David Ellis Beth Anaclerio Kelli L. Kuhen Karen Wolff Kimberly Bieza Badry Bursulaya Tove Tuntland Perry Gordon jeremy caldwell Department of Medicinal Chemistry Genomics Institute of Novartis Research Foundation (GNF)10675 John Hopkins Drive San Diego CA 92121 U.S.A

Non-nucleoside reverse transcriptase inhibitors (NNRTI's) are a major component of the current therapy for AIDS. However, in recent years, significant resistance has been generated against the marketed NNRTI's (nevirapine, delavirdine and efavirenz) due to viral mutations. New NNRTI's are needed to overcome the increasing resistance. We have discovered a novel series of oxindoles that exhibit single digit nanomolar potency against WT HIV and drug-resistant mutants. The synthesis and structure activity relationship (SAR) of this novel series of NNRTI's will be discussed.

关键词： HIV AIDS NNRTI oxindoles SAR

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Implications of de Facto Reuse on Future Regulatory Developments for Beaufort-Jasper Water & Sewer Authority in Okatie, South Carolina, USA

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Journal of Environmental Protection 2024年第2期15卷 173-192页

作者： Tricia H. Kilgore Shubhashini Oza jeremy Hatfield Katherine Y. Bell Department of Technology and Innovation Beaufort-Jasper Water & Sewer Authority Okatie SC USA Department of Research and Innovation Brown and Caldwell Charlotte NC USA Department of Digital Solutions Brown and Caldwell Cleveland OH USA Department of Research and Innovation Brown and Caldwell Nashville TN USA

A significant portion of the national water supply can be attributed to de facto or unplanned potable reuse, though the extent of its contribution is difficult to estimate. Fortunately, the contribution of Water Resource Recovery Facility (WRRF) effluent to waters that supply drinking water treatment plants has been documented by some communities. In the United States (US), among the top 25 most impacted drinking water treatment plants by upstream WRRF, 16% of the influent flow to the drinking water treatment plant under average streamflow and up to 100% under low-flow conditions is WRRF effluent. Currently, the full extent of de facto reuse in the US may be much higher because of population growth. The scenario is no different for Beaufort-Jasper Water and Sewer Authority (BJWSA) in South Carolina, US, with contributions to the Savannah River originating from numerous WRRF and other upstream dischargers. South Carolina coastal utilities such as BJSWA are considering direct and indirect potable reuse options, driven by disposal limitations and challenges. Currently, South Carolina does not have a framework, guidelines, or regulations for reuse, but discussions have started among the regulated community. In addition to understanding the extent of de facto reuse, the state will need to develop standards and best practices to enable future adoption of planned potable reuse solutions to water resources challenges. Such guidance should address human health risk management and technical considerations regarding treatment in addition to other factors, including source control, storage, fail-safe operation, monitoring, non-cost factors, and public acceptance. This study conducted a mapping assessment specific to BJWSA, sampled at four locations on Savannah River, and observed that de facto reuse is approximately 4.6% to 5.9% during low-flow months and is within the range generally observed nationwide. When coupled with evidence that planned potable reuse can improve human h

关键词： Water Reuse De Facto Reuse Planned Potable Reuse Water Recycling Wastewater Derived Contaminants

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