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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)
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)
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)
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)
Annexins are a family of proteins that have been implicated in a range of intracellular processes. In this paper we confirm the existence of annexin V in human platelets (0.02 +/- 0.005% of cell protein). We also demonstrate that 13.7 +/- 6.8% of intracellular annexin V becomes tightly associated with membranes in response to platelet activation by the(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)
We have previously reported that stimulation of platelets causes a relocation of annexin V to the cytoplasmic side of the plasma membrane where it associates with actin. This study examined the association of annexin V with the platelet cytoskeleton and its binding to actin, following both physiological activation with thrombin and Ca2+ -ionophore(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)