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Dyadic Decision Trees This thesis introduces a new family of classifiers called dyadic decision trees (DDTs) and develops their theoretical properties within the framework of statistical learning theory. First, we show that DDTs achieve optimal rates of convergence for a broad range of classification problems and are adaptive in three important respects:(More)
Incubation of platelet-rich plasma (PRP) with ouabain, an inhibitor of sodium/potassium ATPase (Na+/K+ ATPase), induced a significant rise in basal platelet intracellular calcium concentration [( Ca2+]i) when measured using fura 2. Ouabain induced an enhanced aggregation response to low doses of collagen in both PRP and washed platelets loaded with(More)
Platelet activation may occur during immunoglobulin E antibody (IgE)-mediated reactions. In these studies, we confirm that platelet-derived supernatants (PDS) induce histamine release from human mixed leukocytes containing basophils, one of the initial target cells in IgE-mediated reactions. In extending this observation, we have shown that this PDS-induced(More)
We describe the design, synthesis, and optimization of first-in-class series of inhibitors of NADPH oxidase isoform 4 (Nox4), an enzyme implicated in several pathologies, in particular idiopathic pulmonary fibrosis, a life-threatening and orphan disease. Initially, several moderately potent pyrazolopyridine dione derivatives were found during a(More)
Cardiopulmonary bypass (CPB) induces a bleeding defect which leads to enhanced blood loss. A double-blind study was carried out comparing aprotinin with placebo in patients undergoing re-operation for heart valve replacement. The results confirm that aprotinin is effective at reducing such loss. In the placebo treated group, significant increases were(More)
Prostacyclin production by human umbilical artery rings was measured in a variety of incubation media and related to gestational age, mode of delivery, and birth weight. Prostacyclin production was directly correlated with the status of essential free fatty acid in the tissue as assessed by the ratio of tissue concentrations of arachidonic acid and Mead's(More)
The biological half-life of prostacyclin in Krebs solution, human cell-free plasma or whole blood was measured by bracket assay on ADP-induced platelet aggregation. At 37 degrees C, pH 7.4, plasma and blood reduced the rate of loss of antiaggregatory activity compared with Krebs solution. The protective effect of plasma was greater than that of whole blood.(More)
Pyrazolo-pyrido-diazepine, -pyrazine and -oxazine dione derivatives are new chemical entities with good and attractive druglikeness properties. A series of pyrazolo-pyrido-diazepine dione analogs demonstrated to be particularly amenable to lead optimization through a couple of cycles in order to improve specificity for isoforms Nox4 and Nox1 and had(More)
Fresh aortic rings incubated in serum produce more 6-oxo-PGF1 alpha, the stable hydrolysis product of prostacyclin, than in plasma or buffer. A method is described of recovering this stimulatory activity from a dialysate of serum, showing that the activity is due to a prostacyclin stimulating factor. This factor is formed during coagulation initiated by the(More)
Immunocytochemical studies demonstrate that annexin V relocates to the plasma membranes of intact stimulated blood platelets. Anti-annexin V antibodies label the cytoplasmic side of the substrate-adherent plasma membrane of mechanically unroofed, glass-activated platelets and colocalize with actin. In addition, crosslinking experiments using(More)