15 research outputs found

    Seasons, Storms and Seawalls: A Comparison of Constrained and Unconstrained Beaches in Groton, Connecticut

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    A study was done in order to evaluate the impact of a seawall on a beach in Groton, Connecticut. Literature predicts beaches containing seawalls will inhibit functioning as a normal beach and lead to increased erosion. Groton Long Point is developed and backed by a seawall while Bluff Point is located on a state park and receives much less human usage. Profiles were measured to study the effect of storms, seasonality and time on these two barrier beaches. Two transects at each beach were used to determine changes in profiles throughout the year. Profiles were then compared to previous research (Campbell, 2004) to analyze long-term change. The beach at Bluff Point reacted normally to the seasons and the storm and showed a trend of accretion over the four year period. On the other hand, Groton Long Point beach showed no change in beach features in regard to the seasons and storms and exhibited extreme variability in the long-term. While it cannot be proven the seawall at Groton Long Point is increasing erosion, there is strong evidence of erosion on the beach. The irregular system created makes it hard to predict how the beach will behave in the future

    Discovery of biphenylacetamide-derived inhibitors of BACE1 using de novo structure-based molecular design

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    β-Secretase (BACE1), the enzyme responsible for the first and rate-limiting step in the production of amyloid-β peptides, is an attractive target for the treatment of Alzheimer’s disease. In this study, we report the application of the de novo fragment-based molecular design program SPROUT to the discovery of a series of nonpeptide BACE1 inhibitors based upon a biphenylacetamide scaffold. The binding affinity of molecules based upon this designed molecular scaffold was increased from an initial BACE1 IC50 of 323 μM to 27 μM following the synthesis of a library of optimized ligands whose structures were refined using the recently developed SPROUT-HitOpt software. Although a number of inhibitors were found to exhibit cellular toxicity, one compound in the series was found to have useful BACE1 inhibitory activity in a cellular assay with minimal cellular toxicity. This work demonstrates the power of an in silico fragment-based molecular design approach in the discovery of novel BACE1 inhibitors

    Quantifying Uncertainty in Exposure to Coastal Hazards Associated with Both Climate Change and Adaptation Strategies: A U.S. Pacific Northwest Alternative Coastal Futures Analysis

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    Coastal communities face heightened risk to coastal flooding and erosion hazards due to sea-level rise, changing storminess patterns, and evolving human development pressures. Incorporating uncertainty associated with both climate change and the range of possible adaptation measures is essential for projecting the evolving exposure to coastal flooding and erosion, as well as associated community vulnerability through time. A spatially explicit agent-based modeling platform, that provides a scenario-based framework for examining interactions between human and natural systems across a landscape, was used in Tillamook County, OR (USA) to explore strategies that may reduce exposure to coastal hazards within the context of climate change. Probabilistic simulations of extreme water levels were used to assess the impacts of variable projections of sea-level rise and storminess both as individual climate drivers and under a range of integrated climate change scenarios through the end of the century. Additionally, policy drivers, modeled both as individual management decisions and as policies integrated within adaptation scenarios, captured variability in possible human response to increased hazards risk. The relative contribution of variability and uncertainty from both climate change and policy decisions was quantified using three stakeholder relevant landscape performance metrics related to flooding, erosion, and recreational beach accessibility. In general, policy decisions introduced greater variability and uncertainty to the impacts of coastal hazards than climate change uncertainty. Quantifying uncertainty across a suite of coproduced performance metrics can help determine the relative impact of management decisions on the adaptive capacity of communities under future climate scenarios
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