5 research outputs found

    μCAD2NC : a declarative lathe-workplanning model transforming CAD-like geometries into abstract NC programs

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    μCAD2NC is a knowledge-based system generating workplans for idealized lathe CNC machines. It transforms CAD-like geometries of rotational-symmetric workpieces into abstract NC programs, using declarative term representations for all processing steps. The system has been developed using COLAB, a hybrid-knowledge compilation laboratory which integrates the power of forward and backward reasoning (incI. functional programming), constraint propagation, and taxonomic classification. The focus of this work is on exemplifying techniques of the hybrid, declarative COLAB formalisms for the central subtasks of CAD-to-NC transformations

    Reversible Aggregation Plays a Crucial Role on the Folding Landscape of p53 Core Domain

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    The role of tumor suppressor protein p53 in cell cycle control depends on its flexible and partially unstructured conformation, which makes it crucial to understand its folding landscape. Here we report an intermediate structure of the core domain of the tumor suppressor protein p53 (p53C) during equilibrium and kinetic folding/unfolding transitions induced by guanidinium chloride. This partially folded structure was undetectable when investigated by intrinsic fluorescence. Indeed, the fluorescence data showed a simple two-state transition. On the other hand, analysis of far ultraviolet circular dichroism in 1.0 M guanidinium chloride demonstrated a high content of secondary structure, and the use of an extrinsic fluorescent probe, 4,4′-dianilino-1,1′ binaphthyl-5,5′-disulfonic acid, indicated an increase in exposure of the hydrophobic core at 1 M guanidinium chloride. This partially folded conformation of p53C was plagued by aggregation, as suggested by one-dimensional NMR and demonstrated by light-scattering and gel-filtration chromatography. Dissociation by high pressure of these aggregates reveals the reversibility of the process and that the aggregates have water-excluded cavities. Kinetic measurements show that the intermediate formed in a parallel reaction between unfolded and folded structures and that it is under fine energetic control. They are not only crucial to the folding pathway of p53C but may explain as well the vulnerability of p53C to undergo departure of the native to an inactive state, which makes the cell susceptible to malignant transformation
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