Modulating functional loop movements: the role of highly conserved residues in the correlated loop motions

Loop flexibility in enzymes plays a vital role in correctly positioning catalytically important residues. This strong relationship between enzyme flexibility and function provides an opportunity to engineer new substrates and inhibitors. It further allows the design of site-directed mutagenesis experiments to explore enzymatic activity through the control of flexibility of a functional loop. Earlier, we described a novel mechanism in which a small loop triggers the motions of a functional loop in three enzymes (beta-1,4-galactosyltransferase, lipase, and enolase) unrelated in sequence, structure, or function. Here, we further address the question of how the interactions between various flexible loops modulate the movements of the functional loop. We examine beta-1,4-galactosyltransferase as a model system in which a Long loop undergoes a large conformational change (moves in space up to 20 A) upon substrate binding in addition to a small loop (Trp loop) that shows a considerably smaller conformational change. Our molecular-dynamics simulations carried out in implicit and explicit solvent show that, in addition to these two loops, two other neighboring loops are also highly flexible. These loops are in contact with either the Long loop or the Trp loop. Analysis of the covariance of the spatial displacement of the residues reveals that coupled motions occur only in one of these two loops. Sequence analysis indicates that loops correlated in their motions also have highly conserved residues involved in the loop-loop interactions. Further, analysis of crystal structures and simulations in explicit water open the possibility that the Trp loop that triggers the movement of the Long loop in the unbound conformation may also play the same role in the substrate-bound conformation through its contact with the conserved and correlated third loop. Our proposition is supported by the observation that four of the five conserved positions in the third loop are at the interface with the Trp loop. Evolution appears to select residues that drive the functional Long loop to a large conformational change. These observations suggest that altering selected loop-loop interactions might modulate the movements of the functional loop.     

Model based development of access policies

In this paper we present a novel approach for the specification of user rights in the context of an object oriented use case driven development process. Basically, we extend the specification of methods by a permission section describing the right of some actor to call the method of an object. Our approach is both role based and context based while allowing for permissions to be specified at a fine-grained data-dependent level. We use first-order logic with a built-in notion of objects and classes (provided with an algebraic semantics) as our syntactic and semantic framework. In the second part of the paper, we demonstrate the application of this approach in a model-based context to generate permissions in distributed peer-to-peer networks.     

Asking the right questions about leadership: Discussion and conclusions.

Five questions prompted by the articles in the American Psychologist special issue on leadership (January 2007, Vol. 62, No. 1., see records 2006-23492-001, 2006-23492-002, 2006-23492-003, 2006-23492-004, 2006-23492-005, and 2006-23492-006) suggest some new directions for leadership research: (1) Not do leaders make a difference, but under what conditions does leadership matter? (2) Not what are the traits of leaders, but how do leaders' personal attributes interact with situational properties to shape outcomes? (3) Not do there exist common dimensions on which all leaders can be arrayed, but are good and poor leadership qualitatively different phenomena? (4) Not how do leaders and followers differ, but how can leadership models be reformulated so they treat all system members as both leaders and followers? (5) Not what should be taught in leadership courses, but how can leaders be helped to learn? (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Synthesis and materials characterization of Li2MnO3-LiCrO2 system nanocomposite electrode materials

A series of Li[Cr_xLi_(1−x)/3Mn_2(1−x)/3]O₂, (0.2 ≤ x ≤ 0.4) with nanocomposite structures was synthesized by a solution method with subsequent quenching. The sample structures were investigated by X-ray diffraction (Rietveld refinement), electron diffraction and HRTEM. According to co-indexed electron diffraction patterns and HRTEM images, Li[Cr_0.211Li_0.268Mn_0.520]O₂ was found to be composed of solid solution powders and Li[Cr_0.290Li_0.240Mn_0.470]O₂ and Li[Cr_0.338Li_0.225Mn_0.436]O₂ of nanocomposite powders indexed in monoclinic and hexagonal structure. Among the three compounds, the nanocomposite Li[Cr_0.290Li_0.240Mn_0.470]O₂ cathode prevented spinel-like structural transformation during cycling and delivered a good reversible capacity of about 195 mAh/g.     

Leveraging decision‐making tools in capacity building planning: The Indonesian scientific network case

Abstract

The development of investment alternatives for the Government of Indonesia's proposed scientific network forms the background to this case. The goal was to rationalize a structure for developing and sustaining a broad‐based network capable of serving scientists throughout the country, including very remote areas. It became clear that one approach could combine both technological as well as entrepreneurial elements, since the data communications linkages for serving scientists could also be available for private customers. The process of defining and costing out this approach was a textbook example of a bottom‐up analysis, beginning with customer needs and working toward structures to satisfy the needs. The World Bank and the Government of Indonesia are in the process of implementing several features of the recommended system. The proposed approach can ultimately pay for itself through private sector revenues for user services. While the context of the decision is telecommunications, the methodology is appropriate for many decision‐making situations. Samples of actual data and bottom‐line results are discussed.     

Applications of real number theorem proving in PVS

Real number theorem proving has many uses, particularly for verification of safety critical systems and systems for which design errors may be costly. We discuss a chain of developments building on real number theorem proving in PVS. This leads from the verification of aspects of an air traffic control system, through work on the integration of computer algebra and automated theorem proving to a new tool, NRV, first presented here that builds on the capabilities of Maple and PVS to provide a verified and automatic analysis of Nichols plots. This automates a standard technique used by control engineers and greatly improves assurance compared with the traditional method of visual inspection of the Nichols plots.     

Pummelos as Concept Generators for Biomimetically Inspired Low Weight Structures with Excellent Damping Properties

Natural materials often exhibit excellent mechanical properties. An example of outstanding impact resistance is the pummelo fruit (Citrus maxima) which can drop from heights of 10 m and more without showing significant outer damage. Our data suggest that this impact resistance is due to the hierarchical organization of the fruit peel, called pericarp. The project presented in the current paper aims at transferring structural features from the pummelo pericarp to engineering materials, in our case metal foams, produced by the investment casting process. The transfer necessitates a detailed structural and mechanical analysis of the biological model on the one hand, and the identification and development of adequate materials and processes on the other hand. Based on this analysis, engineering composite foam structures are developed and processed which show enhanced damping and impact properties. The modified investment casting process and the model alloy Bi57Sn43 proved to be excellent candidates to make these bio‐inspired structures. Mechanical testing of both the natural and the engineering structures has to consider the necessity to evaluate the impact of the different hierarchical features. Therefore, specimens of largely varying sizes have to be tested and size effects cannot be ignored, especially as the engineering structures might be upscaled in comparison with the natural role model. All in all, the present results are very promising: the basis for a transfer of bio‐inspired structural hierarchical levels has been set.