Prion diseases are associated with the conversion of the normal prion protein, PrP(C), to the infectious disease form PrP(Sc). Discrimination between these isoforms would significantly enhance diagnosis of these diseases, and it has recently been reported that PrP(Sc) is specifically recognized by the serine protease zymogen plasminogen (Fischer et al. (2000) Nature 408, 479). Here we have tested the hypothesis that PrP is a regulator of the plasminogen activation system. The effect of recombinant PrP, either containing copper (holo-PrP) or devoid of it (apo-PrP), on plasminogen activation by both uPA and tPA was determined. PrP had no effect on plasminogen activation by uPA. By contrast, the activity of tPA was stimulated by up to 280-fold. This was observed only with the apo-PrP isoforms. The copper-binding octapeptide repeat region of PrP was involved in the effects, as a mutant lacking this region failed to stimulate plasminogen activation, although a synthetic peptide corresponding to this region was unable to stimulate tPA activity. Competition experiments demonstrated that, in addition to plasminogen binding, the stimulation required a high-affinity interaction between tPA and PrP (K(d) < 2.5 nM). Kinetic analysis revealed a template mechanism for the stimulation, suggesting independent binding sites for tPA and plasminogen. Lack of copper-binding may be an early event in the conversion of PrP(C) to PrP(Sc), and our data therefore suggest that tPA-catalyzed plasminogen activation may provide the basis for a sensitive detection system for the early stages of prion diseases and also play a role in the pathogenesis of these diseases.
Simulated annealing is a provably convergent optimiser for single-objective problems. Previously proposed multiobjective extensions have mostly taken the form of a singleobjective simulated annealer optimising a composite function of the objectives. We propose a multi-objective simulated annealer utilising the relative dominance of a solution as the system energy for optimisation, eliminating problems associated with composite objective functions. We also propose a method for choosing perturbation scalings promoting search both towards and across the Pareto front.We illustrate the simulated annealer's performance on a suite of standard test problems and provide comparisons with another multi-objective simulated annealer and the NSGA-II genetic algorithm. The new simulated annealer is shown to promote rapid convergence to the true Pareto front with a good coverage of solutions across it comparing favourably with the other algorithms.An application of the simulated annealer to an industrial problem, the optimisation of a Code Division Multiple Access (CDMA) mobile telecommunications network's air interface, is presented and the simulated annealer is shown to generate non-dominated solutions with an even and dense coverage that outperform single objective genetic algorithm optimisers.
Introduction: Non-carious lesions are caused as a result of tooth surface loss. Several categories of tooth surface loss exist, including erosion, attrition, abrasion and abfraction. Numerous factors, such as bruxism, clenching, disease, dietary considerations, lifestyle choices, improper tooth brushing, abrasive dentrifices, craniofacial complex, iatrogenic dentistry and ageing might contribute to this problem. It can be challenging to identify the cause, but it is feasible by observing the pattern of tooth surface loss on the teeth, and it is essential for treatment planning to avoid failure. Prevention, tooth remineralization and active treatment by repairing the affected teeth are all methods of managing this process. Treatment options include minimally invasive and adhesive dentistry to full mouth rehabilitation, and restoring the lost vertical height. Case Report: A 45-year-old female patient reported to the Department of Conservative Dentistry and Endodontics with a chief complaint of sensitivity in the upper front teeth for the past 2 months. The clinical examination showed abrasion on the buccal surface of teeth 13 and 23 with dentin exposure. And also, abfraction with respect to 14. No signs of mobility or pain on percussion. Conclusion: The steps of problem identification, diagnosis, etiological factor removal or treatment, and, if necessary, restoration, are components of treating non-caries lesions. The restorative treatment must be considered for dentin hypersensitivity and for the re-establishing of dental esthetics.
Introduction: Internal resorption, which starts in the pulpal cavity, either in the pulpal chamber or in the root canal, is a very uncommon resorption of dentine that continues to destroy the surrounding dental hard tissues. Other aetiological reasons have been proposed; however trauma or persistent pulpal inflammation are likely to be the initial events in internal root resorption. Treatment for minor internal resorption lesions has a favorable prognosis. However, the prognosis is poor and tooth extraction must be considered if the tooth structure has been significantly compromised and perforation has occurred. Case Report: A 36-year-old male patient came to the department with a chief complaint of dull pain in lower right back tooth region in the last one month.The clinical examination showed distal caries in tooth no 45. Caries was also present in tooth no 46. Conclusion: Internal resorption is an uncommon condition with most of cases being idiopathic. The detection of internal resorption can be done in routine radiographs, while others require advanced diagnostic techniques like dental CT scans for its diagnosis
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