In vitro selection and evolution of functional proteins by using ribosome display

We report here a system with which a correctly folded complete protein and its encoding mRNA both remain attached to the ribosome and can be enriched for the ligand-binding properties of the native protein. We have selected a single-chain fragment (scFv) of an antibody 108-fold by five cycles of transcription, translation, antigen-affinity selection, and PCR. The selected scFv fragments all mutated in vitro by acquiring up to four unrelated amino acid exchanges over the five generations, but they remained fully compatible with antigen binding. Libraries of native folded proteins can now be screened and made to evolve in a cell-free system without any transformation or constraints imposed by the host cell.

Dissociation of response conflict, attentional selection, and expectancy with functional magnetic resonance imaging

Two different attentional networks have been associated with visuospatial attention and conflict resolution. In most situations either one of the two networks is active or both are increased in activity together. By using functional magnetic resonance imaging and a flanker task, we show conditions in which one network (anterior attention system) is increased in activity whereas the other (visuospatial attention system) is reduced, showing that attentional conflict and selection are separate aspects of attention. Further, we distinguish between neural systems involved in different forms of conflict. Specifically, we dissociate patterns of activity in the basal ganglia and insula cortex during simple violations in expectancies (i.e., sudden changes in the frequency of an event) from patterns of activity in the anterior attention system specifically correlated with response conflict as evidenced by longer response latencies and more errors. These data provide a systems-level approach in understanding integrated attentional networks.

Altered thymic positive selection and intracellular signals in Cbl-deficient mice

Cbl is the product of the protooncogene c-cbl and is involved in T cell antigen receptor (TCR)-mediated signaling. To understand the role of Cbl for immune system development and function, we generated a Cbl-deficient mouse strain. In Cbl-deficient mice, positive selection of the thymocytes expressing major histocompatibility complex class II-restricted transgenic TCR was significantly enhanced. Two factors may have contributed to the altered thymic selection. First, Cbl deficiency markedly up-regulated the activity of ZAP-70 and mitogen-activated protein kinases. The mitogen-activated protein kinase pathway was shown previously to be involved in thymic positive selection. Second, Cbl-deficient thymocytes expressed CD3 and CD4 molecules at higher levels, which consequently may increase the avidity of TCR/major histocompatibility complex/coreceptor interaction. Thus, Cbl plays a novel role in modulating TCR-mediated multiple signaling pathways and fine-tunes the signaling threshold for thymic selection.

The design and implementation of a repository for the management of spatial data integrity constraints

This paper reviews the key features of an environment to support domain users in spatial information system (SIS) development. It presents a full design and prototype implementation of a repository system for the storage and management of metadata, focusing on a subset of spatial data integrity constraint classes. The system is designed to support spatial system development and customization by users within the domain that the system will operate.

Design and implementation of a windows-based parallel computing environment for large scale optimization

A parallel computing environment to support optimization of large-scale engineering systems is designed and implemented on Windows-based personal computer networks, using the master-worker model and the Parallel Virtual Machine (PVM). It is involved in decomposition of a large engineering system into a number of smaller subsystems optimized in parallel on worker nodes and coordination of subsystem optimization results on the master node. The environment consists of six functional modules, i.e. the master control, the optimization model generator, the optimizer, the data manager, the monitor, and the post processor. Object-oriented design of these modules is presented. The environment supports steps from the generation of optimization models to the solution and the visualization on networks of computers. User-friendly graphical interfaces make it easy to define the problem, and monitor and steer the optimization process. It has been verified by an example of a large space truss optimization. (C) 2004 Elsevier Ltd. All rights reserved.

A case study in specification and implementation testing

Achieving consistency between a specification and its implementation is an important part of software development In previous work, we have presented a method and tool support for testing a formal specification using animation and then verifying an implementation of that specification. The method is based on a testgraph, which provides a partial model of the application under test. The testgraph is used in combination with an animator to generate test sequences for testing the formal specification. The same testgraph is used during testing to execute those same sequences on the implementation and to ensure that the implementation conforms to the specification. So far, the method and its tool support have been applied to software components that can be accessed through an application programmer interface (API). In this paper, we use an industrially-based case study to discuss the problems associated with applying the method to a software system with a graphical user interface (GUI). In particular, the lack of a standardised interface, as well as controllability and observability problems, make it difficult to automate the testing of the implementation. The method can still be applied, but the amount of testing that can be carried on the implementation is limited by the manual effort involved.

Selection and application of risk management tools and techniques for build-operate-transfer projects

Construction projects are risky. However, the characteristics of the risk highly depend on the type of procurement being adopted for managing the project. A build-operate-transfer (BOT) project is recognized as one of the most risky project schemes. There are instances of project failure where a BOT scheme was employed. Ineffective rts are increasingly being managed using various risk management tools and techniques. However, application of those tools depends on the nature of the project, organization's policy, project management strategy, risk attitude of the project team members, and availability of the resources. Understanding of the contents and contexts of BOT projects, together with a thorough understanding of risk management tools and techniques, helps select processes of risk management for effective project implementation in a BOT scheme. This paper studies application of risk management tools and techniques in BOT projects through reviews of relevant literatures and develops a model for selecting risk management process for BOT projects. The application to BOT projects is considered from the viewpoints of the major project participants. Discussion is also made with regard to political risks. This study would contribute to the establishment of a framework for systematic risk management in BOT projects.

Risk based decision support system for effective implementation of projects

Conventional project management techniques are not always sufficient to ensure time, cost and quality achievement of large-scale construction projects due to complexity in planning, design and implementation processes. The main reasons for project non-achievement are changes in scope and design, changes in government policies and regulations, unforeseen inflation, underestimation and improper estimation. Projects that are exposed to such an uncertain environment can be effectively managed with the application of risk management throughout the project's life cycle. However, the effectiveness of risk management depends on the technique through which the effects of risk factors are analysed/quantified. This study proposes the Analytic Hierarchy Process (AHP), a multiple attribute decision making technique, as a tool for risk analysis because it can handle subjective as well as objective factors in a decision model that are conflicting in nature. This provides a decision support system (DSS) to project management for making the right decision at the right time for ensuring project success in line with organisation policy, project objectives and a competitive business environment. The whole methodology is explained through a case application of a cross-country petroleum pipeline project in India and its effectiveness in project management is demonstrated.

Design and implementation of graphical user interfaces for complex simulations

The development of increasingly powerful computers, which has enabled the use of windowing software, has also opened the way for the computer study, via simulation, of very complex physical systems. In this study, the main issues related to the implementation of interactive simulations of complex systems are identified and discussed. Most existing simulators are closed in the sense that there is no access to the source code and, even if it were available, adaptation to interaction with other systems would require extensive code re-writing. This work aims to increase the flexibility of such software by developing a set of object-oriented simulation classes, which can be extended, by subclassing, at any level, i.e., at the problem domain, presentation or interaction levels. A strategy, which involves the use of an object-oriented framework, concurrent execution of several simulation modules, use of a networked windowing system and the re-use of existing software written in procedural languages, is proposed. A prototype tool which combines these techniques has been implemented and is presented. It allows the on-line definition of the configuration of the physical system and generates the appropriate graphical user interface. Simulation routines have been developed for the chemical recovery cycle of a paper pulp mill. The application, by creation of new classes, of the prototype to the interactive simulation of this physical system is described. Besides providing visual feedback, the resulting graphical user interface greatly simplifies the interaction with this set of simulation modules. This study shows that considerable benefits can be obtained by application of computer science concepts to the engineering domain, by helping domain experts to tailor interactive tools to suit their needs.

INTAMAP: the design and implementation of an interoperable automated interpolation web service

INTAMAP is a Web Processing Service for the automatic spatial interpolation of measured point data. Requirements were (i) using open standards for spatial data such as developed in the context of the Open Geospatial Consortium (OGC), (ii) using a suitable environment for statistical modelling and computation, and (iii) producing an integrated, open source solution. The system couples an open-source Web Processing Service (developed by 52°North), accepting data in the form of standardised XML documents (conforming to the OGC Observations and Measurements standard) with a computing back-end realised in the R statistical environment. The probability distribution of interpolation errors is encoded with UncertML, a markup language designed to encode uncertain data. Automatic interpolation needs to be useful for a wide range of applications and the algorithms have been designed to cope with anisotropy, extreme values, and data with known error distributions. Besides a fully automatic mode, the system can be used with different levels of user control over the interpolation process.

Architecture and Implementation of Reporting Means in Adaptive Dynamically Extended Information Systems

This article describes architecture and implementation of subsystem intended for working with queries and reports in adaptive dynamically extended information systems able to dynamically extending. The main features of developed approach are application universality, user orientation and opportunity to integrate with external information systems. Software implementation is based on multilevel metadata approach.

Development and Implementation of NURBS Models of Quadratic Curves and Surfaces

This article goes into the development of NURBS models of quadratic curves and surfaces. Curves and surfaces which could be represented by one general equation (one for the curves and one for the surfaces) are addressed. The research examines the curves: ellipse, parabola and hyperbola, the surfaces: ellipsoid, paraboloid, hyperboloid, double hyperboloid, hyperbolic paraboloid and cone, and the cylinders: elliptic, parabolic and hyperbolic. Many real objects which have to be modeled in 3D applications possess specific features. Because of this these geometric objects have been chosen. Using the NURBS models presented here, specialized software modules (plug-ins) have been developed for a 3D graphic system. An analysis of their implementation and the primitives they create has been performed.

Kontraszelekció és erkölcsi kockázat a politikában. Vázlat az információs aszimmetria közgazdaságtani fogalmainak politikatudományi alkalmazhatóságáról (Negative selection and moral risk in politics. An outline of the usefulness to political science of the economic concept of information asymmetry)

Az írás a kontraszelekció és az erkölcsi kockázat információ-gazdaságtani fogalmának politikatudományi alkalmazhatósága mellett érvel. Azt kívánja bemutatni, hogy a politikai piac szereplői közti információs aszimmetria mechanizmusainak éppúgy lehetnek súlyos negatív hatásai a demokratikus politikai rendszer működésére nézve, mint ahogy a gazdasági szereplők közti információs aszimmetria - Nobel-díjas közgazdászok érvei szerint - alááshatja a piaci verseny hatékonyságát. Az írás új megvilágításba helyezi a - már Platón óta ismert - politikai kontraszelekció jelenségét, továbbá részletesen foglalkozik az erkölcsi kockázat és a megbízó-megbízott relációk megjelenésével a politikában. Érinti tovább azoknak a mechanizmusoknak - a jelzésnek és a szűrésnek - a megjelenését a politikában, melyeket a közgazdászok az információs aszimmetria csökkentésére ajánlanak. / === / The paper argues in favour of employing in political science the economic concept of information asymmetry, seeking to show that the mechanisms of information asymmetry among the players on the political market may have negative effects on the operation of a democratic political system as information asymmetry among economic actors – according to arguments of Nobel prize-winning economists – has on the efficiency of market competition. The paper sheds new light on the phenomenon of negative political selection (known since Plato's time), and goes on to deal in detail with the appearance of moral risk and client/agent relations in politics. The author touches also on the appearance in politics of mechanisms – signals and filters – that economists suggest for reducing information asymmetry.

System design and resource management in the next-generation integrated WLAN and 3G cellular networks

Next-generation integrated wireless local area network (WLAN) and 3G cellular networks aim to take advantage of the roaming ability in a cellular network and the high data rate services of a WLAN. To ensure successful implementation of an integrated network, many issues must be carefully addressed, including network architecture design, resource management, quality-of-service (QoS), call admission control (CAC) and mobility management. ^ This dissertation focuses on QoS provisioning, CAC, and the network architecture design in the integration of WLANs and cellular networks. First, a new scheduling algorithm and a call admission control mechanism in IEEE 802.11 WLAN are presented to support multimedia services with QoS provisioning. The proposed scheduling algorithms make use of the idle system time to reduce the average packet loss of realtime (RT) services. The admission control mechanism provides long-term transmission quality for both RT and NRT services by ensuring the packet loss ratio for RT services and the throughput for non-real-time (NRT) services. ^ A joint CAC scheme is proposed to efficiently balance traffic load in the integrated environment. A channel searching and replacement algorithm (CSR) is developed to relieve traffic congestion in the cellular network by using idle channels in the WLAN. The CSR is optimized to minimize the system cost in terms of the blocking probability in the interworking environment. Specifically, it is proved that there exists an optimal admission probability for passive handoffs that minimizes the total system cost. Also, a method of searching the probability is designed based on linear-programming techniques. ^ Finally, a new integration architecture, Hybrid Coupling with Radio Access System (HCRAS), is proposed for lowering the average cost of intersystem communication (IC) and the vertical handoff latency. An analytical model is presented to evaluate the system performance of the HCRAS in terms of the intersystem communication cost function and the handoff cost function. Based on this model, an algorithm is designed to determine the optimal route for each intersystem communication. Additionally, a fast handoff algorithm is developed to reduce the vertical handoff latency.^