Abstract: The present invention relates to bifunctional compounds, which find utility to degrade and (inhibit) one or more of the following kinases: DYRK1A, DYRK1B, DYRK2, DYRK3, CLKI, CLK2, CLK3, CLK4, and HASPIN. In particular, the present invention is directed to compounds, which contain on one end an E3 ubiquitin ligase binding moiety which binds to an E3 ubiquitin ligase and on the other end a moiety which binds one or more of the following kinases: DYRK1A, DYRK1B, DYRK2, DYRK3, CLK1, CLK2, CLK3, CLK4, and HASPIN, such that the one or more kinases is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of the one or more kinases. The bifunctional compounds serve as therapeutics for the treatment of Alzheimer's disease, down syndrome, diabetes, an autoimmune disease, an inflammatory disorder (e.g., airway inflammation, osteoarthritis (e.g., knee related osteoarthritis)), cancer (e.g.

Abstract: A self-adhesive roll roofing product is configured to form lap joint seams in which a selvage edge portion of one strip of the roofing product is overlapped and bonded to an opposite marginal side edge portion of a next-successive strip of the roofing product. In order to desirably form such a lap joint seam that is resistant to moisture entrapment and blistering, the selvage edge portion of the roofing product is tapered and configured to form a lap joint seam substantially free of void volume and trapped air. A method of making the self-adhesive roll roofing product is also described.

Abstract: A plumbing fixture (10) for carrying drinking water comprised of metal, particularly of copper and its alloys with portions of zinc and lead, which is provided with a lining or coating of tin (18) disposed on at least the interior surface of the fixture.