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1.
Alkema WB Hensgens CM Snijder HJ Keizer E Dijkstra BW Janssen DB 《Protein engineering, design & selection : PEDS》2004,17(5):473-480
Penicillin acylase catalyses the condensation of Calpha-substituted phenylacetic acids with beta-lactam nucleophiles, producing semi-synthetic beta-lactam antibiotics. For efficient synthesis a low affinity for phenylacetic acid and a high affinity for Calpha-substituted phenylacetic acid derivatives is desirable. We made three active site mutants, alphaF146Y, betaF24A and alphaF146Y/betaF24A, which all had a 2- to 10-fold higher affinity for Calpha-substituted compounds than wild-type enzyme. In addition, betaF24A had a 20-fold reduced affinity for phenylacetic acid. The molecular basis of the improved properties was investigated by X-ray crystallography. These studies showed that the higher affinity of alphaF146Y for (R)-alpha-methylphenylacetic acid can be explained by van der Waals interactions between alphaY146:OH and the Calpha-substituent. The betaF24A mutation causes an opening of the phenylacetic acid binding site. Only (R)-alpha-methylphenylacetic acid, but not phenylacetic acid, induces a conformation with the ligand tightly bound, explaining the weak binding of phenylacetic acid. A comparison of the betaF24A structure with other open conformations of penicillin acylase showed that betaF24 has a fixed position, whereas alphaF146 acts as a flexible lid on the binding site and reorients its position to achieve optimal substrate binding. 相似文献
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The focus of this work is a novel application of configurational forces to tendon layout optimisation problems in prestressed concrete beams. To this end, the application of the method of the configurational forces is extended to two-dimensional plane stress analysis. The optimum tendon position is obtained by iteratively arriving at vanishing configurational forces. The performance of the optimisation algorithm is illustrated by means of numerical examples. 相似文献
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Harm op den Akker Valerie M. Jones Hermie J. Hermens 《User Modeling and User-Adapted Interaction》2014,24(5):351-392
Technology mediated healthcare services designed to stimulate patients’ self-efficacy are widely regarded as a promising paradigm to reduce the burden on the healthcare system. The promotion of healthy, active living is a topic of growing interest in research and business. Recent advances in wireless sensor technology and the widespread availability of smartphones have made it possible to monitor and coach users continuously during daily life activities. Physical activity monitoring systems are frequently designed for use over long periods of time placing usability, acceptance and effectiveness in terms of compliance high on the list of design priorities to achieve sustainable behavioral change. Tailoring, or the process of adjusting the system’s behavior to individuals in a specific context, is an emerging topic of interest within the field. In this article we report a survey of tailoring techniques currently employed in state of the art real time physical activity coaching systems. We present a survey of state of the art activity coaching systems as well as a conceptual framework which identifies seven important tailoring concepts that are currently in use and how they relate to each other. A detailed analysis of current use of tailoring techniques in real time physical activity coaching applications is presented. According to the literature, tailoring is currently used only sparsely in this field. We underline the need to increase adoption of tailoring methods that are based on available theories, and call for innovative evaluation methods to demonstrate the effectiveness of individual tailoring approaches. 相似文献
4.
纳米CaCO3合成及原位改性的研究 总被引:3,自引:0,他引:3
在旋转填充床反应器中合成了纳米CaCO3悬浮液,利用pH计跟踪Ca(OH)2碳化反应过程,研究了碳化反应过程原理。结果表明:旋转填充床能极大地强化相间传质与微观混合,提高体系中CaCO3的过饱和度,增大其成核及生长速率。加入适当的添加剂对纳米CaCO3进行原位改性;利用TEM照片研究了原位改性过程中纳米CaCO3的成核生长机理,并考察了添加剂的作用机理。 相似文献
5.
X‐ray diagnostics of plasma deposited thin layers Grazing incidence x‐ray diffractometry (GIXD) and x‐ray reflectometry (XR) have been introduced as well suited tools for investigations of plasma deposited thin layers. They are non‐destructive techniques, therefore a sample can be reused and measured with other techniques. A combination of GIXD and XR can give a range of interesting information about chemical, physical and crystallographic properties of thin films. Conclusions can be drawn how plasma deposition techniques and plasma parameters influence the film growth. In three examples we present the analysis of phase and chemical composition, defect structure and measurements of kinetic process parameters. 相似文献
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Nienke Visser Harm Jan Lourens Gerwin Huls Edwin Bremer Valerie R. Wiersma 《International journal of molecular sciences》2021,22(5)
Elevated activation of the autophagy pathway is currently thought to be one of the survival mechanisms allowing therapy-resistant cancer cells to escape elimination, including for cytarabine (AraC)-resistant acute myeloid leukemia (AML) patients. Consequently, the use of autophagy inhibitors such as chloroquine (CQ) is being explored for the re-sensitization of AraC-resistant cells. In our study, no difference in the activity of the autophagy pathway was detected when comparing AraC-Res AML cell lines to parental AraC-sensitive AML cell lines. Furthermore, treatment with autophagy inhibitors CQ, 3-Methyladenine (3-MA), and bafilomycin A1 (BafA1) did not re-sensitize AraC-Res AML cell lines to AraC treatment. However, in parental AraC-sensitive AML cells, treatment with AraC did activate autophagy and, correspondingly, combination of AraC with autophagy inhibitors strongly reduced cell viability. Notably, the combination of these drugs also yielded the highest level of cell death in a panel of patient-derived AML samples even though not being additive. Furthermore, there was no difference in the cytotoxic effect of autophagy inhibition during AraC treatment in matched de novo and relapse samples with differential sensitivity to AraC. Thus, inhibition of autophagy may improve AraC efficacy in AML patients, but does not seem warranted for the treatment of AML patients that have relapsed with AraC-resistant disease. 相似文献
8.
A new multi‐scale dispersive gradient elasticity model with micro‐inertia: Formulation and
‐finite element implementation 下载免费PDF全文
Dario De Domenico Harm Askes 《International journal for numerical methods in engineering》2016,108(5):485-512
Motivated by nano‐scale experimental evidence on the dispersion characteristics of materials with a lattice structure, a new multi‐scale gradient elasticity model is developed. In the framework of gradient elasticity, the simultaneous presence of acceleration and strain gradients has been denoted as dynamic consistency. This model represents an extension of an earlier dynamically consistent model with an additional micro‐inertia contribution to improve the dispersion behaviour. The model can therefore be seen as an enhanced dynamic extension of the Aifantis' 1992 strain‐gradient theory for statics obtained by including two acceleration gradients in addition to the strain gradient. Compared with the previous dynamically consistent model, the additional micro‐inertia term is found to improve the prediction of wave dispersion significantly and, more importantly, requires no extra computational cost. The fourth‐order equations are rewritten in two sets of symmetric second‐order equations so that ‐continuity is sufficient in the finite element implementation. Two sets of unknowns are identified as the microstructural and macrostructural displacements, thus highlighting the multi‐scale nature of the present formulation. The associated energy functionals and variationally consistent boundary conditions are presented, after which the finite element equations are derived. Considerable improvements over previous gradient models are observed as confirmed by two numerical examples. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
9.
Keulen Ron F.; Adam Jos J.; Fischer Martin H.; Kuipers Harm; Jolles Jelle 《Canadian Metallurgical Quarterly》2002,28(3):515
Students participated in 3 experiments investigating the use of environment- and action-centered reference frames in selective reaching. They pointed to a green target appearing either with or without a red distractor. Target-distractor distance was manipulated, and distractor interference (difference between distractor trials and no-distractor trials) was measured in reaction time, movement time, and movement endpoint. Target-distractor distance determined the dominant frame of reference. Small distances evoked an environment-centered framework that encoded targets within an external context. Large distances evoked an action-centered framework that encoded targets relative to the start position of the hand. Results support the hypothesis that the brain represents spatial information in multiple frames of reference, with the dominant frame of reference being dependent on the task demands. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
10.
Harm Askes Miguel A. Gutirrez 《International journal for numerical methods in engineering》2006,67(3):400-416
A new formulation of gradient elasticity is derived and implemented. Padé approximations are used to introduce an implicit relation between non‐local strains and displacements. As a result, the finite element interpolation requires only ??0‐continuous (rather than ??1‐continuous) shape functions. The underlying energy functional is presented and it is found that the present formulation is of the mixed type, whereby the non‐local strains act as the primary unknowns and the displacements as the auxiliary unknowns. The implications on the interpolation are studied. Finally, the influence of the additional length scale parameter on the global response is assessed. Copyright © 2006 John Wiley & Sons, Ltd. 相似文献