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排序方式: 共有3421条查询结果,搜索用时 14 毫秒
81.
María Conde-Gimnez Juan Jos Galano-Frutos María Galiana-Cameo Alejandro Mahía Bruno L. Victor Sandra Salillas Adrin Velzquez-Campoy Rui M. M. Brito Jos Antonio Glvez María D. Díaz-de-Villegas Javier Sancho 《International journal of molecular sciences》2022,23(9)
Phenylketonuria (PKU) is a rare metabolic disease caused by variations in a human gene, PAH, encoding phenylalanine hydroxylase (PAH), and the enzyme converting the essential amino acid phenylalanine into tyrosine. Many PKU-causing variations compromise the conformational stability of the encoded enzyme, decreasing or abolishing its catalytic activity, and leading to an elevated concentration of phenylalanine in the blood, which is neurotoxic. Several therapeutic approaches have been developed to treat the more severe manifestations of the disorder, but they are either not entirely effective or difficult to adhere to throughout life. In a search for novel pharmacological chaperones to treat PKU, a lead compound was discovered (compound IV) that exhibited promising in vitro and in vivo chaperoning activity on PAH. The structure of the PAH-IV complex has been reported. Here, using alchemical free energy calculations (AFEC) on the structure of the PAH-IV complex, we design a new generation of compound IV-analogues with a higher affinity for the enzyme. Seventeen novel analogues were synthesized, and thermal shift and isothermal titration calorimetry (ITC) assays were performed to experimentally evaluate their stabilizing effect and their affinity for the enzyme. Most of the new derivatives bind to PAH tighter than lead compound IV and induce a greater thermostabilization of the enzyme upon binding. Importantly, the correspondence between the calculated alchemical binding free energies and the experimentally determined ΔΔGb values is excellent, which supports the use of AFEC to design pharmacological chaperones to treat PKU using the X-ray structure of their complexes with the target PAH enzyme. 相似文献
82.
Tomáš Brázdil Javier Esparza Stefan Kiefer Antonín Kučera 《Formal Methods in System Design》2013,43(2):124-163
The paper gives a summary of the existing results about algorithmic analysis of probabilistic pushdown automata and their subclasses. 相似文献
83.
Javier Solano Martínez Jérôme Mulot Fabien Harel Daniel Hissel Marie-Cécile Péra Robert I. John Michel Amiet 《Engineering Applications of Artificial Intelligence》2013,26(7):1772-1779
The aim of this paper is to present experimental validation results of an energy management system for hybrid electrical vehicles based on type-2 fuzzy logic. The energy management system (EMS) is designed by extracting knowledge from several experts using surveys. The consideration of interval type-2 fuzzy sets enables modeling the uncertainty in the answers of the experts. The validation of the EMS is performed on a real-scale heavy duty vehicle equipped with different energy sources such as batteries, fuel cell system and ultracapacitors. Experimental results are strong evidence that type-2 fuzzy logic is wide adapted for performing the energy management in hybrid electrical vehicles. 相似文献
84.
Fermín L. Cruz José A. Troyano Fernando Enríquez F. Javier Ortega Carlos G. Vallejo 《Expert systems with applications》2013,40(8):3174-3184
Nowadays, people do not only navigate the web, but they also contribute contents to the Internet. Among other things, they write their thoughts and opinions in review sites, forums, social networks, blogs and other websites. These opinions constitute a valuable resource for businesses, governments and consumers. In the last years, some researchers have proposed opinion extraction systems, mostly domain-independent ones, to automatically extract structured representations of opinions contained in those texts. In this work, we tackle this task in a domain-oriented approach, defining a set of domain-specific resources which capture valuable knowledge about how people express opinions on a given domain. These resources are automatically induced from a set of annotated documents. Some experiments were carried out on three different domains (user-generated reviews of headphones, hotels and cars), comparing our approach to other state-of-the-art, domain-independent techniques. The results confirm the importance of the domain in order to build accurate opinion extraction systems. Some experiments on the influence of the dataset size and an example of aggregation and visualization of the extracted opinions are also shown. 相似文献
85.
On the measurement of privacy as an attacker’s estimation error 总被引:1,自引:0,他引:1
David Rebollo-Monedero Javier Parra-Arnau Claudia Diaz Jordi Forné 《International Journal of Information Security》2013,12(2):129-149
A wide variety of privacy metrics have been proposed in the literature to evaluate the level of protection offered by privacy-enhancing technologies. Most of these metrics are specific to concrete systems and adversarial models and are difficult to generalize or translate to other contexts. Furthermore, a better understanding of the relationships between the different privacy metrics is needed to enable more grounded and systematic approach to measuring privacy, as well as to assist system designers in selecting the most appropriate metric for a given application. In this work, we propose a theoretical framework for privacy-preserving systems, endowed with a general definition of privacy in terms of the estimation error incurred by an attacker who aims to disclose the private information that the system is designed to conceal. We show that our framework permits interpreting and comparing a number of well-known metrics under a common perspective. The arguments behind these interpretations are based on fundamental results related to the theories of information, probability, and Bayes decision. 相似文献
86.
Carlos Rodriguez Guerrero Juan Carlos Fraile Marinero Javier Perez Turiel Victor Muñoz 《Computer methods and programs in biomedicine》2013
Human motor performance, speed and variability are highly susceptible to emotional states. This paper reviews the impact of the emotions on the motor control performance, and studies the possibility of improving the perceived skill/challenge relation on a multimodal neural rehabilitation scenario, by means of a biocybernetic controller that modulates the assistance provided by a haptic controlled robot in reaction to undesirable physical and mental states. Results from psychophysiological, performance and self assessment data for closed loop experiments in contrast with their open loop counterparts, suggest that the proposed method had a positive impact on the overall challenge/skill relation leading to an enhanced physical human–robot interaction experience. 相似文献
87.
The use of phase change materials (PCM) and their possible architectural integration is a path in the search for optimizing energy efficiency in construction. As part of this path, a pavement has been designed which, in combination with the PCM, serves as a passive thermal conditioning system (new patent n°. ES2333092 A1) [1]. The prototype has been tested experimentally and the results proved that it is a viable constructive solution improving the energy performance of sunny locals. 相似文献
88.
Miguel Vega Javier Mateos Rafael Molina Aggelos K. Katsaggelos 《Journal of Signal Processing Systems》2011,65(3):509-523
In this paper we propose a novel super-resolution based algorithm for the pansharpening of multispectral images. Within the Bayesian formulation, the proposed methodology incorporates prior knowledge on the expected characteristics of multispectral images; that is, it imposes smoothness within each band by means of the energy associated with the ℓ1 norm of vertical and horizontal first order differences of image pixel values and also takes into account the correlation among the bands of the multispectral image. The observation process is modeled using the sensor characteristics of both panchromatic and multispectral images. The method is tested on real and synthetic images, compared with other pansharpening methods, and the quality of the results assessed both qualitatively and quantitatively. 相似文献
89.
Manuel Bethencourt Francisco Javier Botana María José Cano Leandro González-Rovira Mariano Marcos José María Sánchez-Amaya 《Metallurgical and Materials Transactions A》2012,43(1):182-194
A wide variety of anticorrosive treatments for aluminum alloys that can be employed as “green” alternatives to those based on Cr(VI) are currently under development. This article reports a study of the morphological and anticorrosive characteristics of surface layers formed on the Al–Cu alloy AA2017 by immersion treatment in baths of cerium salt, accelerated by increased temperature and the employment of hydrogen peroxide. Scanning electron microscopy (SEM)/X-ray energy dispersive spectroscopy (XEDS) studies of the samples treated have demonstrated the existence of a heterogeneous layer formed by a film of aluminum oxide/hydroxide on the matrix, and a series of dispersed islands of cerium over the cathodic intermetallics. The protective efficacy has been evaluated using electrochemical techniques, linear polarizations (LP) and electrochemical impedance spectroscopy (EIS), and salt spray tests. The results obtained indicate that the layer provided good resistance to corrosion in media with chlorides, and the method gives a considerable reduction of the time required for the immersion treatments. 相似文献
90.
Ricardo M. Souto Yaiza González-García Javier Izquierdo Sergio González 《Corrosion Science》2010,52(3):748-9601
Scanning electrochemical microscopy in feedback mode was used to monitor changes in the surface state of a polymeric film applied on a metallic substrate when exposed to an aqueous electrolytic environment. The protected metal consisted of a carbon steel substrate coated with a polyurethane-based polymeric film. SECM measurements performed in the presence and absence of chloride anions permitted a specific effect caused by Cl− anions at early exposures to be detected. Significant surface roughening is observed for immersion times shorter than 1 day when the electrolyte contains chloride ions. Additionally, the growth of an individual blister could also be investigated. 相似文献