David E. Clark

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This review examines the progress that is being made towards the in silico prediction of brain permeation. Following a brief introduction to the blood-brain barrier, the datasets currently available for in silico modeling are discussed. Recent developments in in silico models of brain permeation are summarized in the context of the current state of the art(More)
An increase in the activity of mitogen-activated protein kinase (MAPK) has been correlated with the progression of prostate cancer to advanced disease in humans. The serine/threonine protein kinase p90-kDa ribosomal S6 kinase (RSK) is an important downstream effector of MAPK but its role in prostate cancer has not previously been examined. Increasing RSK(More)
This article describes the implementation of a new docking approach. The method uses a Tabu search methodology to dock flexibly ligand molecules into rigid receptor structures. It uses an empirical objective function with a small number of physically based terms derived from fitting experimental binding affinities for crystallographic complexes. This means(More)
Seventy adult and pediatric patients with blunt splenic injury were managed nonsurgically using previously published clinical criteria without regard to the appearance of the spleen on computed tomographic (CT) scans. Seven patients (10%) who underwent delayed surgery were considered failures of nonsurgical therapy; all recovered after total splenectomy.(More)
Trauma registries are databases that document acute care delivered to patients hospitalised with injuries. They are designed to provide information that can be used to improve the efficiency and quality of trauma care. Indeed, the combination of trauma registry data at regional or national levels can produce very large databases that allow unprecedented(More)
17beta-Estradiol (E(2)) reduces oxidative stress-induced depolarization of mitochondrial membrane potential (MMP) in cultured human lens epithelial cells (HLE-B3). The mechanism by which the nongenomic effects of E(2) contributed to the protection against mitochondrial membrane depolarization was investigated. Mitochondrial membrane integrity is regulated(More)
BACKGROUND Pediatric colorectal cancer (CRC) is rare. Comparison with adult CRC tumors, management, and outcomes may identify opportunities for improvement in pediatric CRC care. STUDY DESIGN CRC patients in the National Cancer Data Base from 1998 to 2011, were grouped into Pediatric (≤21years), early onset adult (22-50) and older adult (>50) patients.(More)
We report the cases of 3 patients who survived cardiac chamber rupture resulting from blunt external trauma. All were drivers in motor vehicle collisions. All were seen with signs of pericardial tamponade and were treated by pericardiocentesis followed by emergency thoracotomy performed in the operating room. Ruptures of the right atrium and right and left(More)
This paper describes the functionality of a Feature Recognition system, known as FeatureFinder. The system's algorithm has been developed from a graph-based approach to feature recognition and is now capable of identifying a variety of features on a wide range of machined components. The system has been designed to be used within a solids machining package(More)