Robert Howes

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Inhibitors of the Hsp90 molecular chaperone are showing considerable promise as potential chemotherapeutic agents for cancer. Here, we describe the structure-based design, synthesis, structure-activity relationships and pharmacokinetics of potent small-molecule inhibitors of Hsp90 based on the 4,5-diarylisoxazole scaffold. Analogues from this series have(More)
This study evaluated the amount and depth of root resorption associated with varying concentrations and frequencies of injectable, exogenous prostaglandin E2 (PGE2) in conjunction with orthodontic tooth movement in rats. The sample consisted of 155 maxillary right and left first molars from 88, 8-week old, male Sprague-Dawley rats. The animals were divided(More)
The long-term effects of varying concentrations and frequencies of injectable, exogenous prostaglandin E2 (PGE2) on the rate of tooth movement and the amount of root resorption were evaluated. There were 132 male Sprague-Dawley rats 8 weeks old that initially weighed 225 to 250 gm. Five animals were in a pilot study, while seven were baseline controls and(More)
Cell surface sugar residues in neurulating ectoderms of bantam chick embryos of stage 4–11 were examined using ferritin-labeledRicinus communis (RCAI) and Wheat germ agglutinin (WGA). RCAI binding sites densely covered the apical surfaces of the basal plate cells during the neural plate stage (1,322.8±28.8 ferritin particles/μm2). As neural tube formation(More)
Novel piperazinyl, morpholino and piperidyl derivatives of the pyrazole-based Hsp90 inhibitor CCT018159 are described. Structure-activity relationships have been elucidated by X-ray co-crystal analysis of the new compounds bound to the N-terminal domain of human Hsp90. Key features of the binding mode are essentially identical to the recently reported(More)
The purpose of this investigation was to study the changes in temporomandibular joint tissues, in particular the disc and its attachments, associated with muscle-powered continuous posterior displacement of the mandible for 33 days. After measurement of incisal relationships, food and water consumption, histologic and morphometric analysis, and radiologic(More)
Enamel microabrasion using hydrochloric acid and pumice is an effective method to remove superficial enamel discoloration. This procedure is used in many dental offices but little is known about how different treatment combinations of hand applicator pressure on the tooth, number of applications, and duration of application affect the amount of enamel loss.(More)
Wingless is a key morphogen in Drosophila. Although it is evident that Wingless acts at a distance from its site of synthesis, there is considerable debate about how the protein travels across a field of cells. Recent studies have provided important new insights into this process, though the issue is still far from being resolved.