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  • William R Cook, Alan Snyder, Walt Hill, Walter Olthoff, Peter Canning, Chris +15 others
  • 1989
This thesis develops a semantic model of inheritance and investigates its applications for the analysis and design of programming languages. Inheritance is a mechanism for incre-mental programming in the presence of self-reference. This interpretation of inheritance is formalized using traditional techniques of fixed-point theory, resulting in a(More)
Bounded quantification was introduced by Cardelli and Wegner as a means of typing functions that operate uniformly over all subtypes of a given type. They defined a simple " object " model and used bounded quantifica-tion to type-check functions that make sense on all objects having a specified set of " attributes. " A more realistic presentation of(More)
This paper develops a system of explicit interfaces for object-oriented programming. The system provides the benefits of module interfaces found in languages like Ada and Modula-2 while preserving the expressiveness that gives untyped object-oriented languages like Smalltalk their flexibility. Interfaces are interpreted as polymorphic types to make the(More)
Cullin-RING ligases are multisubunit E3 ubiquitin ligases that recruit substrate-specific adaptors to catalyze protein ubiquitylation. Cul3-based Cullin-RING ligases are uniquely associated with BTB adaptors that incorporate homodimerization, Cul3 assembly, and substrate recognition into a single multidomain protein, of which the best known are(More)
The DDR1 receptor tyrosine kinase is activated by matrix collagens and has been implicated in numerous cellular functions such as proliferation, differentiation, adhesion, migration, and invasion. Here we report the discovery of a potent and selective DDR1 inhibitor, DDR1-IN-1, and present the 2.2 Å DDR1 co-crystal structure. DDR1-IN-1 binds to DDR1 in the(More)
E3 ubiquitin ligases that direct substrate proteins to the ubiquitin-proteasome system are promising, though largely unexplored drug targets both because of their function and their remarkable specificity. CRLs [Cullin-RING (really interesting new gene) ligases] are the largest group of E3 ligases and function as modular multisubunit complexes constructed(More)
The discoidin domain receptors (DDRs), DDR1 and DDR2, form a unique subfamily of receptor tyrosine kinases that are activated by the binding of triple-helical collagen. Excessive signaling by DDR1 and DDR2 has been linked to the progression of various human diseases, including fibrosis, atherosclerosis and cancer. We report the inhibition of these unusual(More)
There are currently no effective therapies for fibrodysplasia ossificans progressiva (FOP), a debilitating and progressive heterotopic ossification disease caused by activating mutations of ACVR1 encoding the BMP type I receptor kinase ALK2. Recently, a subset of these same mutations of ACVR1 have been identified in diffuse intrinsic pontine glioma (DIPG)(More)
Tumor suppressors p53, p63 and p73 comprise a family of stress-responsive transcription factors with distinct functions in development and tumor suppression. Most human cancers lose p53 function, yet all three proteins are capable of inducing apoptosis or cellular senescence. Mechanisms are therefore under investigation to activate p73-dependent apoptosis(More)