Multiplex SNP genotyping using Locked Nucleic Acid and microfluidics

Locked Nucleic Acid's or LNA are a new class of bicyclic DNA analogues that have a high affinity and specificity towards complementary nucleic acids. LNA containing oligonucleotides were used to develop a multiplex SNP genotyping assay based entirely on hybridization between capture probe and target. The approach incorporates a polymer microarray platform, photochemistry for immobilization of oligonucleotides onto microarrays, and a dedicated software tool to aid primer and capture probe design for highly multiplex genotyping. Furthermore, these technologies are combined in an integrated microfluidics platform for simple, highly multiplex and robust SNP genotyping.     

Fluorescence Array Scanner Employing a Flying Objective

DNA-based fluorescent microarrays (sometimes called “biochips”) are fast becoming the preferred tool for studying a variety of complex biochemical phenomena ranging from multiplex mutation detection, to gene mapping and expression monitoring, to high throughput screening for new drug candidates. Fluorescence is a low energy phenomenon. The need for rapid, high resolution, wide field imaging of fluorescent microarrays calls for a specialized microscope architecture. We now describe the design of a “Flying Objective” epi-fluorescence microscope that is ideally suited to this application, and compare the performance of this novel instrument with two other commercial epi-fluorescence microscopes designed to read DNA microarrays.     

A concept of local observability

A notion of local observability, which is natural in the context of nonlinear input/output regulation, is introduced. A simple characterization is provided, a comparison is made with other local nonlinear observability definitions, and its behavior under constant-rate sampling is analyzed.     

A computerised construction project management evaluation system

A study approaches to construction project management evaluation revealed inadequacies in for example, the lack of a systematic strategy that is based on clearly defined criteria, historical databanks and standardised techniques. Further study confirmed the need for a computer-based evaluation system that facilitates more realistic assessments, by using relevant criteria, appropriate indicators, suitable tools and a knowledge-based front-end that helps select and integrate the necessary modules from a comprehensive knowledge-bank. Project specific evaluation instruments derived from such a computer-based system are shown to be more efficient in the effective assessment of construction projects and their management.     

Domain decomposition PCG methods for serial and parallel processing

In this paper two domain decomposition formulations are presented in conjunction with the preconditioned conjugate gradient method (PCG) for the solution of large-scale problems in solid and structural mechanics. In the first approach, the PCG method is applied to the global coefficient matrix, while in the second approach it is applied to the interface problem after eliminating the internal degrees of freedom. For both implementations, a subdomain-by-subdomain (SBS) polynomial preconditioner is employed, based on local information of each subdomain. The approximate inverse of the global coefficient matrix or the Schur complement matrix, which acts as the preconditioner, is expressed by a truncated Neumann series resulting in an additive type local preconditioner. Block type preconditioning, where full elimination is performed inside each block, is also studied and compared with the proposed polynomial preconditioning.     

Microfluidic Enabling Platform for Cell-based Assays

We have developed proprietary technologies for executing continuous flow assays in biochips which mimic human capillaries. Such technologies are integral to the rapidly growing laboratory instrumentation sector for applications in drug discovery, biotechnology, medical diagnostics and environmental studies. A common link between all sectors is the movement toward miniaturization to increase throughput, accuracy and efficiency in the development of new drugs. The miniaturization process itself leads to a demand for new instruments and tools capable of handling microlitre quantities of biological fluids and reagents, thus, we present an instrument which is capable of doing so in the form of a microfluidic enabling platform.     

A simulation model for eliciting scheduling knowledge: an application to the precast manufacturing process

This paper discusses the process of eliciting scheduling knowledge from a simulation model and the development of a dynamic modelling approach to the scheduling process in the precast concrete industry. Due to the problems associated with eliciting scheduling knowledge from an ‘expert’ in the precast industry or perhaps in most of the manufacturing industries, simulation is used to complement human knowledge in this paper. Such knowledge will be used for online support to advise production schedulers and for further development of the simulation model by incorporating the knowledge in the model and making it more dynamic. The paper suggests that dynamic selection of scheduling rules during real-time operation has been recognised as a promising approach to the scheduling process in the precast industry. For this strategy to work effectively, sufficient knowledge is required to enable the model to predict the most effective scheduling rule to meet current factory status. The paper concludes that if the knowledge rules are used effectively, they could be a considerable managerial tool for exploring and improving managerial practices. Recommendations have been made regarding the development of a more realistic and practical scheduling system.     

A computer-aided system to improve production rates in construction

Production rates for similar activities on construction sites can vary considerably. Many factors can produce these variations in addition to the shear dynamics associated with any construction project. Factors which influence production rates and methods in order to improve the accuracy of estimates are considered in this paper. Better estimates are obtained from a detailed analysis of factors occurring at the work site. To determine what these factors might be, field observations were made of construction activities using video and time study techniques. The knowledge and data gathered from these observations were combined with the knowledge acquired from literature sources, questionnaires, and interviews with experts in construction to form a knowledge-base. This cumulative knowledge was then used to create an expert system, or estimating tool, which prompts less experienced estimators to consider the complex factors which affect production rates.     

Global controllability of linear autonomous systems: A geometric consideration

The global controllability in finite time of a linear autonomous system with restrained controls is investigated. Necessary and sufficient conditions are obtained by an approach based on the consideration of geometric properties of the system.     

An extension of the Bene filter and some identification problems solved by nonlinear filtering methods

An extension of Benne ' filtering theorem to time dependent, parameter dependent and unknown initial conditions filtering problems is proved. A new approach for the identification of linear diffusions with unknown drift coefficients follows. New finite dimensional filters, which may also be regarded as identification filters, are derived and related to W.S. Wong's earlier work which used algebraic methods.     

Engineering An Experimental Platform For High Throughput Reactivity Screening

The genomics revolution coupled to advances in computational power, informatics and robotics is driving drug discovery programs to produce drug candidates faster. This need has resulted in advances in high throughput methods for performing organic chemistry such as combinatorial and parallel synthesis. Yet there has not been a corollary advance in the ability to collect quantitative information on reactions that can be used to produce these drug candidates. This lack of an efficient and robust analytical method has resulted in a significant chemistry bottleneck. This work outlines a set of methods that helps address this chemistry bottleneck by using analytical constructs to detect and quantify reaction outcomes. To accomplish this, an integrated experimentalcheminformatics platform has been developed which couples an experimental design system, automated high throughput parallel and combinatorial synthesis methodology, sample processing, quantitative mass spectroscopy and automated data analysis. This platform is being used to optimize single reactions and the syntheses of whole libraries of compounds, and to generate large databases on specific reaction classes.     

Functional integration in CAD systems

This paper examines the issue of integration in CAD systems and argues that for integration to be effective, it must address the functional aspects of a CAD system. It discusses the need for integrated systems and, within a structural engineering context, identifies several facets of integration that should be targeted. These include 2-D drafting and 3-D modelling, graphical and nongraphical design information, the CAD data structure and its user interface, as well as integration of the drafting function with other engineering applications. Means of achieving these levels of integration are briefly discussed and a prognosis for the future development of integrated systems explored. Particular attention is paid to the emergence (and potential role) of ‘product models’ which seek to encapsulate the full range of data elements required to define completely an engineering artefact.     

A Demonstration of High-Throughput Electrophoresis

Automating electrophoresis significantly reduces the time required for loading a large number of samples, increases the speed of electrophoresis analysis, and maximizes the resolution power (clear separation of fragments) of this technique. In addition, automation increases the precision of electrophoresis analysis. Here we demonstrate an automated, high-throughput method of loading 96 samples simultaneously onto an electrophoresis gel, using the Apogent Discoveries Tango™ system and the Invitrogen™ E-Gel® 96 system.     

A note on the Hankel norm

It is shown that the triangle inequality for the Hankel norm of a stable, linear time-invariant system can be derived using properties of the system's controllability and observability Gramians.     

A simple framework for real-time cryptographic protocol analysis with compositional proof rules

A real-time process algebra, enhanced with specific constructs for handling cryptographic primitives, is proposed to model cryptographic protocols in a simple way. We show that some security properties, such as authentication and secrecy, can be re-formulated in this timed setting. Moreover, we show that they can be seen as suitable instances of a general information flow-like scheme, called timed generalized non-deducibility on compositions (tGNDC), parametric w.r.t. the observational semantics of interest. We show that, when considering timed trace semantics, there exists a most powerful hostile environment (or enemy) that can try to compromise the protocol. Moreover, we present a couple of compositionality results for tGNDC, one of which is time dependent, and show their usefulness by means of a case study.     

A finite and an infinite Whittaker integral transform

This paper is concerned with the construction and study of specific finite and infinite integral transforms arising from a singular Sturm-Liouville problem on a half line, which is connected to the hydrogen atom equation. The paper goes further to describe fully the image of some spaces of square integrable functions with respect to some measure under the finite and infinite integral transforms.     

A new measure of consistency for positive reciprocal matrices

The analytic hierarchy process (AHP) provides a decision maker with a way of examining the consistency of entries in a pairwise comparison matrix and the hierarchy as a whole through the consistency ratio measure. It has always seemed to us that this commonly used measure could be improved upon. The purpose of this paper is to present an alternative consistency measure and demonstrate how it might be applied in different types of matrices.