A hybrid molecular dynamics/fluctuating hydrodynamics method for modelling liquids at multiple scales in space and time

A new 3D implementation of a hybrid model based on the analogy with two-phase hydrodynamics has been developed for the simulation of liquids at microscale. The idea of the method is to smoothly combine the atomistic description in the molecular dynamics zone with the Landau-Lifshitz fluctuating hydrodynamics representation in the rest of the system in the framework of macroscopic conservation laws through the use of a single "zoom-in" user-defined function s that has the meaning of a partial concentration in the two-phase analogy model. In comparison with our previous works, the implementation has been extended to full 3D simulations for a range of atomistic models in GROMACS from argon to water in equilibrium conditions with a constant or a spatially variable function s. Preliminary results of simulating the diffusion of a small peptide in water are also reported.

A simple, sensitive and selective quantum-dot-based western blot method for the simultaneous detection of multiple targets from cell lysates

Quantum dots (Qdots) are fluorescent nanoparticles that have great potential as detection agents in biological applications. Their optical properties, including photostability and narrow, symmetrical emission bands with large Stokes shifts, and the potential for multiplexing of many different colours, give them significant advantages over traditionally used fluorescent dyes. Here, we report the straightforward generation of stable, covalent quantum dot-protein A/G bioconjugates that will be able to bind to almost any IgG antibody, and therefore can be used in many applications. An additional advantage is that the requirement for a secondary antibody is removed, simplifying experimental design. To demonstrate their use, we show their application in multiplexed western blotting. The sensitivity of Qdot conjugates is found to be superior to fluorescent dyes, and comparable to, or potentially better than, enhanced chemiluminescence. We show a true biological validation using a four-colour multiplexed western blot against a complex cell lysate background, and have significantly improved previously reported non-specific binding of the Qdots to cellular proteins.

Visualising and controlling the flow in biomolecular systems at and between multiple scales:from atoms to hydrodynamics at different locations in time and space

A novel framework for modelling biomolecular systems at multiple scales in space and time simultaneously is described. The atomistic molecular dynamics representation is smoothly connected with a statistical continuum hydrodynamics description. The system behaves correctly at the limits of pure molecular dynamics (hydrodynamics) and at the intermediate regimes when the atoms move partly as atomistic particles, and at the same time follow the hydrodynamic flows. The corresponding contributions are controlled by a parameter, which is defined as an arbitrary function of space and time, thus, allowing an effective separation of the atomistic 'core' and continuum 'environment'. To fill the scale gap between the atomistic and the continuum representations our special purpose computer for molecular dynamics, MDGRAPE-4, as well as GPU-based computing were used for developing the framework. These hardware developments also include interactive molecular dynamics simulations that allow intervention of the modelling through force-feedback devices.

A novel, dynamic, in vivo, non-contact method of measuring oxygen depletion rate of the anterior eye

Despite the importance of oxygen measurements, techniques have been limited by their invasive nature and small corneal area of assessment. The aim of this study was to assess a non-contact way of measuring oxygen uptake of the whole anterior eye.

Evidence and implications of multiple paradigms in accounting knowledge production

This paper uses evidence gathered in two perception studies ofAustralasian and British accounting academics to reflect on aspects of the knowledge production systemwithin accounting academe. We provide evidence of the representation of multiple paradigms in many journals that are scored by participants as being of high quality. Indeed most of the journals we surveyed are perceived by accounting academics as incorporating research from more than one paradigm. It is argued that this ‘catholic’ approach by journal editors and the willingness of many respondents in our surveys to score journals highly on material they publish from both paradigm categories reflects a balanced acceptance of the multi-paradigmatic state of accounting research. Our analysis is set within an understanding of systems of accounting knowledge production as socially constructed and as playing an important role in the distribution of power and reward in the academy. We explore the impact of our results on concerns emerging from the work of a number of authors who carefully expose localised 'elites'. The possibilities for a closer relationship between research emerging from a multi-paradigm discipline and policy setting and practice are also discussed. The analysis provides a sense of optimism that the broad constituency of accounting academics operates within an environment conducive for the exchange of ideas. That optimism is dampened by concerns about the impact of local 'elites' and the need for more research on their impact on accounting academe.

Recovery of multiple amplitude levels from a DQPSK NRZ signal using a single Mach-Zehnder Interferometer

In this research the recovery of a DQPSK signal will be demonstrated using a single Mach-Zehnder Interferometer (MZI). By changing the phase delay in one of the arms it will be shown that different delays will produce different output levels. It will also be shown that with a certain level of phase shift the DQPSK signal can be converted into four different equally spaced optical power levels. With each decoded level representing one of the four possible bit permutations. By using this additional phase shift in one of the arms the number of MZIs required for decoding can be reduced from two to one.

Structure and dynamics of multiple cationic vectors-siRNA complexation by all-atomic molecular dynamics simulations

Understanding the molecular mechanism of gene condensation is a key component to rationalizing gene delivery phenomena, including functional properties such as the stability of the gene-vector complex and the intracellular release of the gene. In this work, we adopt an atomistic molecular dynamics simulation approach to study the complexation of short strand duplex RNA with four cationic carrier systems of varying charge and surface topology at different charge ratios. At lower charge ratios, polymers bind quite effectively to siRNA, while at high charge ratios, the complexes are saturated and there are free polymers that are unable to associate with RNA. We also observed reduced fluctuations in RNA structures when complexed with multiple polymers in solution as compared to both free siRNA in water and the single polymer complexes. These novel simulations provide a much better understanding of key mechanistic aspects of gene-polycation complexation and thereby advance progress toward rational design of nonviral gene delivery systems.

Ophthalmological manifestations of multiple sclerosis

Optic neuritis, as a result of the formation of demyelination plaques in the optic nerve, is one of the commonest early symptoms of multiple sclerosis. Hence, it is important that optometrists are aware of the symptoms of optic neuritis and of the conditions with which it can be confused. However, only a proportion of patients with optic neuritis will develop the symptoms of multiple sclerosis. The first part of the article describes the symptoms and differential diagnosis of optic neuritis and its relationship with multiple sclerosis. In the second part of the article, the variety of visual changes and symptoms which can be observed in multiple sclerosis patients will be described.

Immunoinformatic evaluation of multiple epitope ensembles as vaccine candidates:E coli 536

Epitope prediction is becoming a key tool for vaccine discovery. Prospective analysis of bacterial and viral genomes can identify antigenic epitopes encoded within individual genes that may act as effective vaccines against specific pathogens. Since B-cell epitope prediction remains unreliable, we concentrate on T-cell epitopes, peptides which bind with high affinity to Major Histacompatibility Complexes (MHC). In this report, we evaluate the veracity of identified T-cell epitope ensembles, as generated by a cascade of predictive algorithms (SignalP, Vaxijen, MHCPred, IDEB, EpiJen), as a candidate vaccine against the model pathogen uropathogenic gram negative bacteria Escherichia coli (E-coli) strain 536 (O6:K15:H31). An immunoinformatic approach was used to identify 23 epitopes within the E-coli proteome. These epitopes constitute the most promiscuous antigenic sequences that bind across more than one HLA allele with high affinity (IC50 <50nM). The reliability of software programmes used, polymorphic nature of genes encoding MHC and what this means for population coverage of this potential vaccine are discussed.

Developments and extensions of Roth's method of double Fourier series with applications to the solution of electromagnetic field problems

The first part of the thesis compares Roth's method with other methods, in particular the method of separation of variables and the finite cosine transform method, for solving certain elliptic partial differential equations arising in practice. In particular we consider the solution of steady state problems associated with insulated conductors in rectangular slots. Roth's method has two main disadvantages namely the slow rate of con­vergence of the double Fourier series and the restrictive form of the allowable boundary conditions. A combined Roth-separation of variables method is derived to remove the restrictions on the form of the boundary conditions and various Chebyshev approximations are used to try to improve the rate of convergence of the series. All the techniques are then applied to the Neumann problem arising from balanced rectangular windings in a transformer window. Roth's method is then extended to deal with problems other than those resulting from static fields. First we consider a rectangular insulated conductor in a rectangular slot when the current is varying sinusoidally with time. An approximate method is also developed and compared with the exact method.The approximation is then used to consider the problem of an insulated conductor in a slot facing an air gap. We also consider the exact method applied to the determination of the eddy-current loss produced in an isolated rectangular conductor by a transverse magnetic field varying sinusoidally with time. The results obtained using Roth's method are critically compared with those obtained by other authors using different methods. The final part of the thesis investigates further the application of Chebyshdev methods to the solution of elliptic partial differential equations; an area where Chebyshev approximations have rarely been used. A poisson equation with a polynomial term is treated first followed by a slot problem in cylindrical geometry.

General features of Multiple System Atrophy

Multiple system atrophy (MSA) is a rare movement disorder and a member of a group of neurodegenerative diseases referred to collectively as the ‘parkinsonian syndromes’. Characteristic of these syndromes is that the patient exhibits symptoms of ‘parkinsonism’, viz., a range of problems involving movement, most typically manifest in Parkinson’s disease (PD) itself1, but also seen in progressive supranuclear palsy (PSP), and to some extent in dementia with Lewy bodies (DLB). MSA is a relatively ‘new’ descriptive term and is derived from three previously described diseases, viz., olivopontocerebellar atrophy, striato-nigral degeneration, and Shy-Drager syndrome. The classical symptoms of MSA include parkinsonism, ataxia, and autonomic dysfunction.6 Ataxia describes a gross lack of coordination of muscle movements while autonomic dysfunction involves a variety of systems that regulate unconscious bodily functions such as heart rate, blood pressure, bladder function, and digestion. Although primarily a neurological disorder, patients with MSA may also develop visual signs and symptoms that could be useful in differential diagnosis. The most important visual signs may include oculomotor dysfunction and problems in pupil reactivity but are less likely to involve aspects of primary vision such as visual acuity, colour vision, and visual fields. In addition, the eye-care practitioner can contribute to the management of the visual problems of MSA and therefore, help to improve quality of life of the patient. Hence, this first article in a two-part series describes the general features of MSA including its prevalence, signs and symptoms, diagnosis, pathology, and possible causes.

Visual signs and symptoms of Multiple System Atrophy

Multiple system atrophy (MSA) is a rare movement disorder and a member of a group of neurodegenerative diseases, which include Parkinson’s disease (PD) and progressive supranuclear palsy (PSP), and referred to as the ‘parkinsonian syndromes’. Although primarily a neurological disorder, patients with MSA may also develop visual signs and symptoms that could be useful in differential diagnosis. In addition, the eye-care practitioner may contribute to the management of visual problems of MSA patients and therefore, help to improve quality of life. This second article in the series considers the visual signs and symptoms of MSA with special reference to those features most useful in differential diagnosis of the parkinsonian syndromes.