Ubiquitin specific protease 7 (USP7) has attracted increasing attention because of its multifaceted roles in different tumor types. The crystal structures of USP7-inhibitor complexes resolved recently provide reliable...
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Ubiquitin specific protease 7 (USP7) has attracted increasing attention because of its multifaceted roles in different tumor types. The crystal structures of USP7-inhibitor complexes resolved recently provide reliable models for computational structure-based drug design (SBDD) towards USP7. How to accurately estimate USP7-ligand binding affinity is quite critical to guarantee the reliability of SBDD. In this study, we assessed the reliability of multiple computational methods to the binding affinity prediction for a series of USP7 inhibitors with the pyrimidinone scaffold, including molecular docking scoring, MM/PB(GB)SA, and umbrella sampling (US). It was found that the accuracy of the evaluated computational methods for binding affinity prediction follows the order: US-based method > MM/PB(GB)SA > Glide XP scoring. The calculation results demonstrate that incorporating protein flexibility through induced-fit docking or ensemble docking cannot improve the performance of the Glide scoring based on rigid-receptor docking. For the MM/PB(GB)SA methods, the choice of the protein structure and the calculation procedure has a marked impact on the predictions. More importantly, we discovered for the first time that there are significant differences in the dissociation pathways of strong-binding inhibitors and weak-binding inhibitors of USP7, which may be used as a new criterion to judge whether an inhibitor is a strong binder or not. It is expected that our work can provide valuable guidance on the design and discovery of potent USP7 inhibitors.
Four N-substituted and two NN-disubstituted acetamides of related structures were studied with NMR spectroscopic and/or computational methods (force field, semiempirical and Hartree-Fock ab initio codes). The rotamers...
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Four N-substituted and two NN-disubstituted acetamides of related structures were studied with NMR spectroscopic and/or computational methods (force field, semiempirical and Hartree-Fock ab initio codes). The rotamers and the conformers were mapped. A possible extension of the amide conjugation and the existance/non-existance of the rotamers were explored. (c) 2006 Elsevier B.V. All rights reserved.
This paper describes a new methodology to predict and analyze rotorcraft noise, This methodology includes 1) a combined computational fluid dynamics and Kirchhoff scheme for far-field noise predictions, 2) parallel co...
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This paper describes a new methodology to predict and analyze rotorcraft noise, This methodology includes 1) a combined computational fluid dynamics and Kirchhoff scheme for far-field noise predictions, 2) parallel computer implementation of the Kirchhoff integrations, 3) audio and visual rendering of the computed acoustic predictions over large far-field regions, and 4) acoustic tracebacks to the Kirchhoff surface to pinpoint the sources of the rotor noise. This paper describes each method and presents sample results for three test cases, The first case consists of in-plane high-speed impulsive noise, and the other two cases show idealized parallel and oblique blade-vortex interactions, The computed results show good agreement with available experimental data, but convey much more information about the far-field noise propagation, When taken together, these analysis techniques exploit the power of new computer technologies and offer the potential to significantly improve our prediction and understanding of rotorcraft noise.
The proceedings contain 43 papers. The topics discussed include: study on static and creep properties of CFRP using rubber modified matrix;testing of palm fibre as reinforcement material in polyester composites;experi...
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ISBN:
(纸本)9781845640804
The proceedings contain 43 papers. The topics discussed include: study on static and creep properties of CFRP using rubber modified matrix;testing of palm fibre as reinforcement material in polyester composites;experimental study on fracture behaviour of polycrystalline ceramics under shock loading;blocking and self-locking of superdislocations in intermetallics;the properties and performance of polymer fibre reinforced bituminous mixtures;hardness determination of EBiD-layers containing tungsten and cobalt;an investigation into martensitic transformation in hot stamping process;quantitative assessment of strain and heat treatment on twin formation in commercially pure nickel;three-dimensional crystallographic characterization and mechanical modeling of a commercial stainless steel;and impedance spectroscopy as a tool to study modifications in the microstructure of concrete in ionic migration experiments.
The volume of available data has been growing exponentially, increasing data problem's complexity and obscurity. In response, visual analytics (VA) has gained attention, yet its solutions haven't scaled well f...
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The volume of available data has been growing exponentially, increasing data problem's complexity and obscurity. In response, visual analytics (VA) has gained attention, yet its solutions haven't scaled well for big data. computational methods can improve VA's scalability by giving users compact, meaningful information about the input data. However, the significant computation time these methods require hinders real-time interactive visualization of big data. By addressing crucial discrepancies between these methods and VA regarding precision and convergence, researchers have proposed ways to customize them for VA. These approaches, which include low-precision computation and iteration-level interactive visualization, ensure real-time interactive VA for big data.
In order to verify and validate the computational methods for neutron flux calculation in TRIGA research reactor calculations a series of experiments has been performed The neutron activation method was used to verify...
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In order to verify and validate the computational methods for neutron flux calculation in TRIGA research reactor calculations a series of experiments has been performed The neutron activation method was used to verify the calculated neutron flux distribution in the TRIGA reactor Aluminium (99 9 wt%)-Gold (0 1 wt%) foils (disks of 5 mm diameter and 02 mm thick) were irradiated in 33 locations 6 in the core and 27 in the carrousel facility in the reflector The experimental results were compared to the calculations performed with Monte Carlo code MCNP using detailed geometrical model of the reactor The calculated and experimental normalized reaction rates in the core are in very good agreement for both isotopes indicating that the material and geometrical properties of the reactor core are modelled well In conclusion one can state that our computational model describes very well the neutron flux and reaction rate distribution in the reactor core In the reflector however the accuracy of the epithermal and thermal neutron flux distribution and attenuation is lower mainly due to lack of information about the material properties of the graphite reflector surrounding the core but the differences between measurements and calculations are within 10% Since our computational model properly describes the reactor core it can be used for calculations of reactor core parameters and for optimization of research reactor utilization (C) 2010 Elsevier Ltd All rights reserved
Nowadays, lasers are used in a wide variety of manufacturing processes, such as cutting, sintering and welding. The evolution of laser technologies has led to the creation of ultrashort pulsed lasers, with a pulse dur...
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Nowadays, lasers are used in a wide variety of manufacturing processes, such as cutting, sintering and welding. The evolution of laser technologies has led to the creation of ultrashort pulsed lasers, with a pulse duration below 10 ps, which have the ability, on the contrary with the conventional lasers, to stimulate separately the electrons and the lattice. Thus, two different temperatures, the electron temperature and the lattice temperature appear. This cannot be described by the classical Fourier heat equations and thus the Two-Temperature Model (TTM) has been proposed. In the TTM, a heat equation that describes the electron temperature is conjugated with a heat equation that describes the lattice temperature. Except from the correct implementation of the heat equations, other factors that should be taken into consideration during the development of the TTM simulation are the correct and accurate modelling of the ultrashort pulsed laser and the appropriate selection of the computational method regarding the targets of each specific study. The aim of this review paper is not only to present the current literature regarding the different TTMs, ultrashort pulsed laser models and computational methods, but also to create mind maps that will help the researcher to choose the most appropriate TTM and computational method regarding the targets of each specific study. Moreover, in this review paper, recommendations for future work are given, regarding the more accurate and realistic modelling of the laser source.
Computing systems are rapidly changing with multicore, graphics processing units (GPUs), clusters, volunteer systems, clouds, and grids offering a confusing dazzling array of opportunities. New programming paradigms s...
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Computing systems are rapidly changing with multicore, graphics processing units (GPUs), clusters, volunteer systems, clouds, and grids offering a confusing dazzling array of opportunities. New programming paradigms such as Google MapReduce and many-task computing have joined the traditional repertoire of workflow and parallel computing for the highest performance systems. Meanwhile, the life sciences are continuing to expand in data generated with continuing improvement in the instruments for high-throughput analysis. This ‘fourth paradigm’ (data driven science) is joined by complex systems or biocomplexity that can build phenomenological models of biological systems and processes. This special issue for Emerging computational methods for the Life Sciences Workshop ECMLS2012 [1], juxtaposes these trends seeking those computational methods that will enhance scientific discovery. Within this overall scope, this special issue encouraged researchers to submit and present original work related to the latest trends in parallel and distributed high-performance systems applied to life science problems.
Mass flowrate is very important, as it determines the frontal area, volume, size, and weight of the engine, and consequently, the momentum drag at certain flight conditions, specific fuel consumption, and the aircraft...
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Mass flowrate is very important, as it determines the frontal area, volume, size, and weight of the engine, and consequently, the momentum drag at certain flight conditions, specific fuel consumption, and the aircraft total loading. The mass flowrate is also needed to determine the shaft power and the thrust power developed by the engine when the specific work output is obtained. Different computational methods have been used in this research to find out their relative accuracy in determining the mass flow passing through an already designed, but not built, stage. The methods employed are free vortex variation of density using approximate scheme including mean radius, arithmetic average density, and numerical integration using the trapezoidal and Simpson's rule. Moreover, closed-form integration (theoretical) with free vortex, linear variation, and parabolic variation of density along the height of the blade was considered. The arithmetic average method was found to give the highest accuracy. The mean-radius method is the least accurate but the simplest. Hence, it is advised to be used especially in quick estimates.. The difference in accuracy is not so great to justify using tedious and time-consuming methods.
This paper attempts to construct a sound basis to support real-time negotiation decision-making by carefully applying concepts from the area of computational geometry, to meet the increasing decision requirements of e...
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This paper attempts to construct a sound basis to support real-time negotiation decision-making by carefully applying concepts from the area of computational geometry, to meet the increasing decision requirements of electronic commerce. To achieve this, a method is discussed that models decision preferences and traces exact or close matches to these preferences in real-time, therefore allowing the decision maker to form a starting point of negotiations, while being realistic in individual expectations. The paper also discusses the implications and restrictions of such an approach and its future application in the deployment of decision support systems. (C) 2002 Elsevier Science B.V. All rights reserved.
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