Okadaic acid-induced lens epithelial cell apoptosis requires inhibition of phosphatase-1 and is associated with induction of gene expression including p53 and bax

We report the 2.2 A resolution structure of the Drosophila engrailed homeodomain bound to its optimal DNA site. The original 2.8 A resolution structure of this complex provided the first detailed three-dimensional view of how homeodomains recognize DNA, and has served as the basis for biochemical studies, structural studies and molecular modeling. Our refined structure confirms the principal conclusions of the original structure, but provides important new details about the recognition interface. Biochemical and NMR studies of other homeodomains had led to the notion that Gln50 was an especially important determinant of specificity. However, our refined structure shows that this side-chain makes no direct hydrogen bonds to the DNA. The structure does reveal an extensive network of ordered water molecules which mediate contacts to several bases and phosphates (including contacts from Gln50), and our model provides a basis for detailed comparison with the structure of an engrailed Q50K altered-specificity variant. Comparing our structure with the crystal structure of the free protein confirms that the N and C termini of the homeodomain become ordered upon DNA-binding. However, we also find that several key DNA contact residues in the recognition helix have the same conformation in the free and bound protein, and that several water molecules also are "preorganized" to contact the DNA. Our structure helps provide a more complete basis for the detailed analysis of homeodomain-DNA interactions.     

Exploring the genetic and environmental etiology of high general cognitive ability in fourteen- to thirty-six-month-old twins

Two definitions of normality ("isolated" or "correlated") are considered. The boundaries of "isolated" normality were determined by a statistical procedure, whereas the "correlated" approach was related to a clinical or predictive definition. In the latter case, the biological variations were considered abnormal if they implied a hazard with some significant future ailment as a risk factor. In this pragmatic approach, the upper limit of normal/abnormal variations is the point beyond which medical strategy is related to the most expected benefit when applied to a definite population or to an individual patient. The capacity of a diagnostic test to discriminate between patients with a defined risk and those without risk depends strictly on the value of the parameter chosen. In medical care for the prevention of vascular complications in diabetic patients or with foetal risks in pregnant women, the limits of the so-called normal range of glycaemia and other parameters should be determined according to the objective of the preventive and/or therapeutic measures to be prescribed.     

Aerosol MALDI with a Reflectron Time-of-Flight Mass Spectrometer

Aerosol matrix-assisted laser desorption/ionization (MALDI) has been combined with a reflectron time-of-flight mass spectrometer for improved mass resolution. A methanol solution of matrix and analyte was sprayed directly into a reflectron time-of-flight mass spectrometer, and the aerosol particles were irradiated and ionized with a frequency-tripled Nd:YAG laser at 355 nm. Mass resolution of over 300 was observed for the peptides bradykinin, angiotensin II, and gramicidin D and for vitamin B(12). This represents a resolution enhancement of approximately 10-fold over that previously reported for aerosol MALDI with a linear time-of-flight instrument.     

A new scalable multicast routing algorithm for interactive real-time applications

Quality of service (QoS) provisioning generally assumes more than one QoS measure that implies that QoS routing can be categorized as an instance of routing subject to multiple constraints: delay jitter, bandwidth, cost, etc. We study the problem of constructing multicast trees to meet the QoS requirements of real-time interactive applications where it is necessary to provide bounded delays and bounded delay variation among the source and all destinations while keeping overall cost of the multicast tree low. The main contribution of our work is a new strategy for constructing multiconstrained multicast trees. We first derive mathematically a new delay-variation estimation scheme and prove its efficiency. Thereafter, we propose a simple and competitive (in terms of running time) heuristic algorithm, for delay and delay variation constrained routing problem based on the proposed delay-variation estimation scheme and using the Extended Prim-Dijkstra tradeoffs’ algorithm. Our contribution also extends previous works in providing some properties and analyses of delay bounded paths satisfying delay variation constraints. Extensive simulation results show that our algorithm outperforms DVDMR in terms of multicast delay variation with the same time complexity as DVDMR.     

Performance analysis of security aspects by weaving scenarios extracted from UML models

Aspect-oriented modeling (AOM) allows software designers to describe features that address pervasive concerns separately as aspects, and to systematically incorporate the features into a design model using model composition techniques. The goal of this paper is to analyze the performance effects of different security features that may be represented as aspect models. This is part of a larger research effort to integrate methodologies and tools for the analysis of security and performance properties early in the software development process. In this paper, we describe an extension to the AOM approach that provides support for performance analysis. We use the performance analysis techniques developed previously in the PUMA project, which take as input UML models annotated with the standard UML Profile for Schedulability, Performance and Time (SPT), and transform them first into Core Scenario Model (CSM), and then into different performance models. The composition of the aspects with the primary (base) model is performed at the CSM level. A new formal definition of CSM properties and operations is described as a foundation for scenario-based weaving. The proposed approach is illustrated with an example that utilizes two standards, TPC-W and SSL.     

Using Developer Activity Data to Enhance Awareness during Collaborative Software Development

Software development is a global activity unconstrained by the bounds of time and space. A major effect of this increasing scale and distribution is that the shared understanding that developers previously acquired by formal and informal face-to-face meetings is difficult to obtain. This paper proposes a shared awareness model that uses information gathered automatically from developer IDE interactions to make explicit orderings of tasks, artefacts and developers that are relevant to particular work contexts in collaborative, and potentially distributed, software development projects. The research findings suggest that such a model can be used to: identify entities (developers, tasks, artefacts) most associated with a particular work context in a software development project; identify relevance relationships amongst tasks, developers and artefacts e.g. which developers and artefacts are currently most relevant to a task or which developers have contributed to a task over time; and, can be used to identify potential bottlenecks in a project through a ‘social graph’ view. Furthermore, this awareness information is captured and provided as developers work in different locations and at different times.     

The BIOPHILE Sample Process Management System - Automated Sample Access at Ultra Low Temperatures

The genomics, proteomics, clinical, and drug discovery laboratories have a growing need to maintain valuable samples at ultra-low (−80°C) temperatures in a validated, secure environment. Automated sample processing systems have until now required manual (off-line) storage of samples at −80°C, reducing system reliability and speed. Both of these important needs are addressed by the Sample Process Management System being introduced by BIOPHILE Inc. Conventional sample management processes, such as storage, retrieval, and cataloging, are increasingly strained by the growing sample populations. There are variable sample types, access requirements and storage requirements. Security and inventory procedures are implemented manually. The evolving technologies present in the laboratory cannot interface with conventional manual storage techniques. Addressing these limitations, the primary benefits of BIOPHILE's solutions are:

• Fully validated sample management process that coordinates the life-cycles of samples and their related data.

• Robotic technology to securely store and retrieve samples, improving their accessibility and stability. Thermal shock is reduced, improving sample longevity and quality. The robotic technology allows integration with larger automation systems.

• A process program to develop a Sample Management Strategy. This strategy is developed by analyzing long-term research goals, current baseline processes, and identification of current sample life cycles. A full validation documentation package can be generated, providing a high level of quality assurance.

• Improved sample visibility and quality assurance - automated sample population cataloging; controlled sample management access and security.

     

1994 construction outlook: Dodge/Sweet's finds bright spots for 1994

Constrained by the excesses of the previous decade and tepid performance in the general economy, the rebound by construction from its 1990-91 downturn could best be described as subdued and selective. Single-family housing led the way before faltering this year, and only scattered help has come from the industry's other sectors. The big question facing construction at the end of 1993 is whether the current recovery is in danger of stalling or, put differently, does it have the stamina to become more broad-based?