Novel miniaturized systems in high-throughput screening

High-throughput screening (HTS) using high-density microplates is the primary method for the discovery of novel lead candidate molecules. However, new strategies that eschew 2D microplate technology, including technologies that enable mass screening of targets against large combinatorial libraries, have the potential to greatly increase throughput and decrease unit cost. This review presents an overview of state-of-the-art microplate-based HTS technology and includes a discussion of emerging miniaturized systems for HTS. We focus on new methods of encoding combinatorial libraries that promise throughputs of as many as 100 000 compounds per second.

Boundary value problems for systems of difference equations associated with systems of second-order ordinary differential equations

We study difference equations which arise as discrete approximations to two-point boundary value problems for systems of second-order ordinary differential equations. We formulate conditions which guarantee a priori bounds on first differences of solutions to the discretized problem. We establish existence results for solutions to the discretized boundary value problems subject to nonlinear boundary conditions. We apply our results to show that solutions to the discrete problem converge to solutions of the continuous problem in an aggregate sense. (C) 2002 Elsevier Science Ltd. All rights reserved.

Universal simulation of Hamiltonian dynamics for quantum systems with finite-dimensional state spaces

What interactions are sufficient to simulate arbitrary quantum dynamics in a composite quantum system? Dodd [Phys. Rev. A 65, 040301(R) (2002)] provided a partial solution to this problem in the form of an efficient algorithm to simulate any desired two-body Hamiltonian evolution using any fixed two-body entangling N-qubit Hamiltonian, and local unitaries. We extend this result to the case where the component systems are qudits, that is, have D dimensions. As a consequence we explain how universal quantum computation can be performed with any fixed two-body entangling N-qudit Hamiltonian, and local unitaries.

Nutritional strategies for the prevention of hypocalcaemia at calving for dairy cows in pasture-based systems

This review considers the current literature on the macro-mineral nutrition of the soon-to-calve, or transition, dairy cow. Calcium is the main focus, since milk fever (clinical hypocalcaemia) appears to be the most common mineral-related problem faced by the transition cow Australia-wide. The importance of minimising calcium intake and optimising the balance of the key dietary electrolytes, sodium, potassium, sulfate, and chloride, in the weeks before calving is highlighted. Excess dietary potassium can, in some situations, induce milk fever, perhaps even more effectively than excess calcium. Excess sodium remains under suspicion. In contrast, excess dietary chlorine and, to a lesser extent, sulfur can improve the ability of the cow to maintain calcium homeostasis. Diets that promote either a hypomagnesaemia or hyperphosphataemia have also the potential to precipitate milk fever at calving. Current prevention strategies focus on the use of forages with moderate to low levels of calcium, potassium, and sodium, and also rely on or utilise addition of chloride and sulfate in the form of 'anionic' feeds. Anionic salts are one example of an anionic feed. However, legitimate questions remain as to the effectiveness of anionic salts in pasture-feeding systems. The causes and prevention of milk fever are considered from the perspective of the variety of Australian feedbases. Impediments to the use of anionic feeds in Australia feeding systems are outlined. The potential for improving maternal reserves of calcium around calving to reduce the risk of milk fever is also discussed.

Phase variable restriction-modification systems in Moraxella catarrhalis

A repetitive DNA motif was used as a marker to identify novel genes in the mucosal pathogen Moraxella catarrhalis. There is a high prevalence of such repetitive motifs in virulence genes that display phase variable expression. Two repeat containing loci were identified using a digoxigenin-labelled 5'-(CAAC)(6)-3' oligonucleotide probe. The repeats are located in the methylase components of two distinct type III restriction-modification (R-M) systems. We suggest that the phase variable nature of these R-M systems indicates that they have an important role in the biology of M. catarrhalis. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Microbiological Societies.

Partial automation of database processing of simulation outputs from L-systems models of plant morphogenesis

Models of plant architecture allow us to explore how genotype environment interactions effect the development of plant phenotypes. Such models generate masses of data organised in complex hierarchies. This paper presents a generic system for creating and automatically populating a relational database from data generated by the widely used L-system approach to modelling plant morphogenesis. Techniques from compiler technology are applied to generate attributes (new fields) in the database, to simplify query development for the recursively-structured branching relationship. Use of biological terminology in an interactive query builder contributes towards making the system biologist-friendly. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Perp-systems and partial geometries

A perp-system R(r) is a maximal set of r-dimensional subspaces of PG(N,q) equipped with a polarity rho, such that the tangent space of an element of R(r) does not intersect any element of R(r). We prove that a perp-system yields partial geometries, strongly regular graphs, two-weight codes, maximal arcs and k-ovoids. We also give some examples, one of them yielding a new pg(8,20,2).

The development and psychometric properties of a measure of social and adaptive functioning for children and adolescents

Developed, piloted, and examined the psychometric properties of the Child and Adolescent Social and Adaptive Functioning Scale (CASAFS), a self-report measure designed to examine the social functioning of young people in the areas of school performance, peer relationships, family relationships, and home duties/self-care. The findings of confirmatory and exploratory factor analysis support a 4-factor solution consistent with the hypothesized domains. Fit indexes suggested that the 4-correlated factor model represented a satisfactory solution for the data, with the covariation between factors being satisfactorily explained by a single, higher order factor reflecting social and adaptive functioning in general. The internal consistency and 12-month test-retest reliability of the total scale was acceptable. A significant, negative correlation was found between the CASAFS and a measure of depressive symptoms, showing that high levels of social functioning are associated with low levels of depression. Significant differences in CASAFS total and subscale scores were found between clinically depressed adolescents and a matched sample of nonclinical controls. Adolescents who reported elevated but subclinical levels of depression also reported lower levels of social functioning in comparison to nonclinical controls.

A uniform white-noise model for fixed-point roundoff errors in digital systems

Fixed-point roundoff noise in digital implementation of linear systems arises due to overflow, quantization of coefficients and input signals, and arithmetical errors. In uniform white-noise models, the last two types of roundoff errors are regarded as uniformly distributed independent random vectors on cubes of suitable size. For input signal quantization errors, the heuristic model is justified by a quantization theorem, which cannot be directly applied to arithmetical errors due to the complicated input-dependence of errors. The complete uniform white-noise model is shown to be valid in the sense of weak convergence of probabilistic measures as the lattice step tends to zero if the matrices of realization of the system in the state space satisfy certain nonresonance conditions and the finite-dimensional distributions of the input signal are absolutely continuous.

Geography's emerging cross-disciplinary links: Process, causes, outcomes and challenges

In Australian universities the discipline of Geography has been the pace-setter in forging cross-disciplinary links to create multidisciplinary departments and schools, well ahead of other disciplines in humanities, social sciences and sciences, and also to a greater extent than in comparable overseas university systems. Details on all cross-disciplinary links and on immediate outcomes have been obtained by surveys of all heads of departments/schools with undergraduate Geography programs. These programs have traced their own distinctive trajectories, with ramifying links to cognate fields of enquiry, achieved through mergers, transfers, internal initiatives and, more recently, faculty-wide restructuring to create supradisciplinary schools. Geography's `exceptionalism' has proved short-lived. Disciplinary flux is now extending more widely within Australian universities, driven by a variety of internal and external forces, including: intellectual questioning and new ways of constituting knowledge; technological change and the information revolution; the growth of instrumentalism and credentialism, and managerialism and entre-preneurial imperatives; reinforced by a powerful budgetary squeeze. Geographers are proving highly adaptive in pursuit of cross-disciplinary connections, offering analytical tools and selected disciplinary insights useful to non-geographers. However, this may be at cost to undergraduate programs focussing on Geography's intellectual core. Whereas formerly Geography had high reproductive capacity but low instrumental value it may now be in a phase of enhanced utility but perilously low reproductive capacity.

Contribution of cholinergic systems to state-dependent modulation of respiratory control

Respiration is altered during different stages of the sleep-wake cycle. We review the contribution of cholinergic systems to this alteration, with particular reference to the role of muscarinic acetylcholine receptors (MAchRs) during rapid eye movement (REM) sleep. Available evidence demonstrates that MAchRs have potent excitatory effects on medullary respiratory neurones and respiratory motoneurones, and are likely to contribute to changes in central chemosensitive drive to the respiratory control system. These effects are likely to be most prominent during REM sleep, when cholinergic brainstem neurones show peak activity levels. It is possible that MAchR dysfunction is involved in sleep-disordered breathing, Such as obstructive sleep apnea. (C) 2002 Elsevier Science B.V. All rights reserved.