Functional neuroimaging and behavioural studies on global form processing in the human visual system

Magnetoencephalography (MEG), functional magnetic resonance imaging (fMRI) and behavioural experiments were used to investigate the neural processes underlying global form perception in human vision. Behavioural studies using Glass patterns examined sensitivity for detecting radial, rotational and horizontal structure. Neuroimaging experiments using either Glass patterns or arrays of Gabor patches determined the spatio-temporal neural responseto global form. MEG data were analysed using synthetic aperture magnetometry (SAM) to spatially map event-related cortical oscillatory power changes: the temporal sequencing of activity within a discrete cortical area was determined using a Morlet wavelet transform. A case study was conducted to determine the effects of strbismic amblyopia on global form processing: all other observers were normally-sighted. The main findings from normally-sighted observers were: 1) sensitivity to horizontal structure was less than for radial or rotational structure; 2) the neural response to global structure was a reduction in cortical oscillatory power (10-30 Hz) within a network of extrastriate areas, including V4 and V3a; 3) the extend of reduced cortical power was least for horizontal patters; 4) V1 was not identified as a region of peak activity with either MEG or fMRI. The main findings with the strabismic amblyope were: 1) sensitivity for detection of radial, rotational, and horizontal structure was reduced when viewed with the amblyopic- relative to the fellow- eye; 2) cortical power changes within V4 to the presentation of rotational Glass patterns were less when viewed with the amblyopic- compared with the fellow- eye. The main conclusions are: 1) a network of extrastriate cortical areas are involved in the analysis of global form, with the most prominent change in neural activity being a reduction in oscillatory power within the 10-30 Hz band; 2) in strabismic amblyopia, the neuronal assembly associated with form perception in extrastriate cortex may be dysfunctional, the nature of this dysfunction may be a change in the normal temporal pattern of neuronal discharges; 3) MEG, fMRI and behavioural measures support the notion that different neural processes underlie the perception of horizontal as opposed to radial or rotational structure.

An optical study of human ocular dimensions

Many workers have studied the ocular components which occur in eyes exhibiting differing amounts of central refractive error but few have ever considered the additional information that could be derived from a study of peripheral refraction. Before now, peripheral refraction has either been measured in real eyes or has otherwise been modelled in schematic eyes of varying levels of sophistication. Several differences occur between measured and modelled results which, if accounted for, could give rise to more information regarding the nature of the optical and retinal surfaces and their asymmetries. Measurements of ocular components and peripheral refraction, however, have never been made in the same sample of eyes. In this study, ocular component and peripheral refractive measurements were made in a sample of young near-emmetropic, myopic and hyperopic eyes. The data for each refractive group was averaged. A computer program was written to construct spherical surfaced schematic eyes from this data. More sophisticated eye models were developed making use of linear algebraic ray tracing program. This method allowed rays to be traced through toroidal aspheric surfaces which were translated or rotated with respect to each other. For simplicity, the gradient index optical nature of the crystalline lens was neglected. Various alterations were made in these eye models to reproduce the measured peripheral refractive patterns. Excellent agreement was found between the modelled and measured peripheral refractive values over the central 70o of the visual field. This implied that the additional biometric features incorporated in each eye model were representative of those which were present in the measured eyes. As some of these features are not otherwise obtainable using in vivo techniques, it is proposed that the variation of refraction in the periphery offers a very useful optical method for studying human ocular component dimensions.

Measurement of ocular component contributions to residual astigmatism in adult human eyes

The aim of this study was to determine whether an ophthalmophakometric technique could offer a feasible means of investigating ocular component contributions to residual astigmatism in human eyes. Current opinion was gathered on the prevalence, magnitude and source of residual astigmatism. It emerged that a comprehensive evaluation of the astigmatic contributions of the eye's internal ocular surfaces and their respective axial separations (effectivity) had not been carried out to date. An ophthalmophakometric technique was developed to measure astigmatism arising from the internal ocular components. Procedures included the measurement of refractive error (infra-red autorefractometry), anterior corneal surface power (computerised video keratography), axial distances (A-scan ultrasonography) and the powers of the posterior corneal surface in addition to both surfaces of the crystalline lens (multi-meridional still flash ophthalmophakometry). Computing schemes were developed to yield the required biometric data. These included (1) calculation of crystalline lens surface powers in the absence of Purkinje images arising from its anterior surface, (2) application of meridional analysis to derive spherocylindrical surface powers from notional powers calculated along four pre-selected meridians, (3) application of astigmatic decomposition and vergence analysis to calculate contributions to residual astigmatism of ocular components with obliquely related cylinder axes, (4) calculation of the effect of random experimental errors on the calculated ocular component data. A complete set of biometric measurements were taken from both eyes of 66 undergraduate students. Effectivity due to corneal thickness made the smallest cylinder power contribution (up to 0.25DC) to residual astigmatism followed by contributions of the anterior chamber depth (up to 0.50DC) and crystalline lens thickness (up to 1.00DC). In each case astigmatic contributions were predominantly direct. More astigmatism arose from the posterior corneal surface (up to 1.00DC) and both crystalline lens surfaces (up to 2.50DC). The astigmatic contributions of the posterior corneal and lens surfaces were found to be predominantly inverse whilst direct astigmatism arose from the anterior lens surface. Very similar results were found for right versus left eyes and males versus females. Repeatability was assessed on 20 individuals. The ophthalmophakometric method was found to be prone to considerable accumulated experimental errors. However, these errors are random in nature so that group averaged data were found to be reasonably repeatable. A further confirmatory study was carried out on 10 individuals which demonstrated that biometric measurements made with and without cycloplegia did not differ significantly.

Psychophysical investigations of human peripheral vision

This thesis investigates various aspects of peripheral vision, which is known not to be as acute as vision at the point of fixation. Differences between foveal and peripheral vision are generally thought to be of a quantitative rather than a qualitative nature. However, the rate of decline in sensitivity between foveal and peripheral vision is known to be task dependent and the mechanisms underlying the differences are not yet well understood. Several experiments described here have employed a psychophysical technique referred to as 'spatial scaling'. Thresholds are determined at several eccentricities for ranges of stimuli which are magnified versions of one another. Using this methodology a parameter called the E2 value is determined, which defines the eccentricity at which stimulus size must double in order to maintain performance equivalent to that at the fovea. Experiments of this type have evaluated the eccentricity dependencies of detection tasks (kinetic and static presentation of a differential light stimulus), resolution tasks (bar orientation discrimination in the presence of flanking stimuli, word recognition and reading performance), and relative localisation tasks (curvature detection and discrimination). Most tasks could be made equal across the visual field by appropriate magnification. E2 values are found to vary widely dependent on the task, and possible reasons for such variations are discussed. The dependence of positional acuity thresholds on stimulus eccentricity, separation and spatial scale parameters is also examined. The relevance of each factor in producing 'Weber's law' for position can be determined from the results.

Neuro-electromagnetic imaging of the human visual cortex

Methods of solving the neuro-electromagnetic inverse problem are examined and developed, with specific reference to the human visual cortex. The anatomy, physiology and function of the human visual system are first reviewed. Mechanisms by which the visual cortex gives rise to external electric and magnetic fields are then discussed, and the forward problem is described mathematically for the case of an isotropic, piecewise homogeneous volume conductor, and then for an anisotropic, concentric, spherical volume conductor. Methods of solving the inverse problem are reviewed, before a new technique is presented. This technique combines prior anatomical information gained from stereotaxic studies, with a probabilistic distributed-source algorithm to yield accurate, realistic inverse solutions. The solution accuracy is enhanced by using both visual evoked electric and magnetic responses simultaneously. The numerical algorithm is then modified to perform equivalent current dipole fitting and minimum norm estimation, and these three techniques are implemented on a transputer array for fast computation. Due to the linear nature of the techniques, they can be executed on up to 22 transputers with close to linear speedup. The latter part of the thesis describes the application of the inverse methods to the analysis of visual evoked electric and magnetic responses. The CIIm peak of the pattern onset evoked magnetic response is deduced to be a product of current flowing away from the surface areas 17, 18 and 19, while the pattern reversal P100m response originates in the same areas, but from oppositely directed current. Cortical retinotopy is examined using sectorial stimuli, the CI and CIm ;peaks of the pattern onset electric and magnetic responses are found to originate from areas V1 and V2 simultaneously, and they therefore do not conform to a simple cruciform model of primary visual cortex.

Substances hazardous to health:the nature of the expertise associated with competent risk assessment

This research investigated expertise in hazardous substance risk assessment (HSRA). Competent pro-active risk assessment is needed to prevent occupational ill-health caused by hazardous substance exposure occurring in the future. In recent years there has been a strong demand for HSRA expertise and a shortage of expert practitioners. The discipline of Occupational Hygiene was identified as the key repository of knowledge and skills for HSRA and one objective of this research was to develop a method to elicit this expertise from experienced occupational hygienists. In the study of generic expertise, many methods of knowledge elicitation (KE) have been investigated, since this has been relevant to the development of 'expert systems' (thinking computers). Here, knowledge needed to be elicited from human experts, and this stage was often a bottleneck in system development, since experts could not explain the basis of their expertise. At an intermediate stage, information collected was used to structure a basic model of hazardous substance risk assessment activity (HSRA Model B) and this formed the basis of tape transcript analysis in the main study with derivation of a 'classification' and a 'performance matrix'. The study aimed to elicit the expertise of occupational hygienists and compare their performance with other health and safety professionals (occupational health physicians, occupational health nurses, health and safety practitioners and trainee health and safety inspectors), as evaluated using the matrix. As a group, the hygienists performed best in the exercise, and this group were particularly good at process elicitation and at recommending specific control measures, although the other groups also performed well in selected aspects of the matrix and the work provided useful findings and insights. From the research, two models of HSRA have been derived, an HSRA aid, together with a novel videotape KE technique and interesting research findings. The implications of this are discussed with respect to future training of HS professionals and wider application of the videotape KE method.

Tear analysis and lens-tear interactions:part II. Ocular lipids-nature and fate of meibomian gland phospholipids

Purpose: Published data indicate that the polar lipid content of human meibomian gland secretions (MGS) could be anything between 0.5% and 13% of the total lipid. The tear film phospholipid composition has not been studied in great detail and it has been understood that the relative proportions of lipids in MGS would be maintained in the tear film. The purpose of this work was to determine the concentration of phospholipids in the human tear film. Methods: Liquid chromatography mass spectrometry (LCMS) and thin layer chromatography (TLC) were used to determine the concentration of phospholipid in the tear film. Additionally, an Amplex Red phosphatidylcholine-specific phospholipase C (PLC) assay kit was used for determination of the activity of PLC in the tear film. Results: Phospholipids were not detected in any of the tested human tear samples with the low limit of detection being 1.3 µg/mL for TLC and 4 µg/mL for liquid chromatography mass spectrometry. TLC indicated that diacylglycerol (DAG) may be present in the tear film. PLC was in the tear film with an activity determined at approximately 15 mU/mL, equivalent to the removal of head groups from phosphatidylcholine at a rate of approximately 15 µM/min. Conclusions: This work shows that phospholipid was not detected in any of the tested human tear samples (above the lower limits of detection as described) and suggests the presence of DAG in the tear film. DAG is known to be at low concentrations in MGS. These observations indicate that PLC may play a role in modulating the tear film phospholipid concentration.

Future research on human resource management systems in Asia

Re-emphasizing the need to examine human resource management (HRM) in context, this article builds around four themes. First, it analyses the main issues discussed in the existing literature regarding HRM in the Asian context. Second, it highlights the critical challenges facing HRM function in the region. Third, along with the analysis, it presents an agenda for future research. Fourth, it presents a framework useful for highlighting the context specific nature of Asian HRM functions and the main determinants of HRM policies and practices from a cross-national comparative perspective.

Improving recombinant human adenosine A2A receptor production in yeast

Over 50% of clinically-marketed drugs target membrane proteins; in particular G protein-coupled receptors (GPCRs). GPCRs are vital to living cells, performing an active role in many processes, making them integral to drug development. In nature, GPCRs are not sufficiently abundant for research and their structural integrity is often lost during extraction from cell membranes. The objectives of this thesis were to increase recombinant yield of the GPCR, human adenosine A2A receptor (hA2AR) by investigating bioprocess conditions in large-scale Pichia pastoris and small-scale Saccharomyces cerevisiae cultivations. Extraction of hA2AR from membranes using novel polymers was also investigated. An increased yield of hA2AR from P. pastoris was achieved by investigating the methanol feeding regime. Slow, exponential feed during induction (μlow) was compared to a faster, exponential feed (μhigh) in 35 L pilot-scale bioreactors. Overall hA2AR yields were increased for the μlow cultivation (536.4pmol g-1) compared to the μhigh148.1 pmol g-1. hA2AR levels were maintained in cytotoxic methanol conditions and unexpectedly, pre-induction levels of hA2AR were detected. Small-scale bioreactor work showed that Design of Experiments (DoE) could be applied to screen for bioprocess conditions to give optimal hA2AR yields. Optimal conditions were retrieved for S. cerevisiae using a d-optimal screen and response surface methodology. The conditions were 22°C, pH 6.0, 30% DO without dimethyl sulphoxide. A polynomial equation was generated to predict hA2AR yields if conditions varied. Regarding the extraction, poly (maleic anhydride-styrene) or PMAS was successful in solubilising hA2AR from P. pastoris membranes compared with dodcecyl-β-D-maltoside (DDM) detergent. Variants of PMAS worked well as solubilising agents with either 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) or cholesteryl hemisuccinate (CHS). Moreover, esterification of PMAS improved solubilisation, suggesting that increased hydrophobicity stabilises hA2AR during extraction. Overall, hA2AR yields were improved in both, P. pastoris and S. cerevisiae and the use of novel polymers for efficient extraction was achieved.

Transglutaminases:nature's biological glues

Transglutaminases (Tgases) are a widely distributed group of enzymes that catalyse the post-translational modification of proteins by the formation of isopeptide bonds. This occurs either through protein cross-linking via epsilon-(gamma-glutamyl)lysine bonds or through incorporation of primary amines at selected peptide-bound glutamine residues. The cross-linked products, often of high molecular mass, are highly resistant to mechanical challenge and proteolytic degradation, and their accumulation is found in a number of tissues and processes where such properties are important, including skin, hair, blood clotting and wound healing. However, deregulation of enzyme activity generally associated with major disruptions in cellular homoeostatic mechanisms has resulted in these enzymes contributing to a number of human diseases, including chronic neurodegeneration, neoplastic diseases, autoimmune diseases, diseases involving progressive tissue fibrosis and diseases related to the epidermis of the skin. In the present review we detail the structural and regulatory features important in mammalian Tgases, with particular focus on the ubiquitous type 2 tissue enzyme. Physiological roles and substrates are discussed with a view to increasing and understanding the pathogenesis of the diseases associated with transglutaminases. Moreover the ability of these enzymes to modify proteins and act as biological glues has not gone unnoticed by the commercial sector. As a consequence, we have included some of the present and future biotechnological applications of this increasingly important group of enzymes.

The challenges of representing human behaviour in simulation models:some case examples from supply chain, evacuation modelling and rail disruption

As more of the economy moves from traditional manufacturing to the service sector, the nature of work is becoming less tangible and thus, the representation of human behaviour in models is becoming more important. Representing human behaviour and decision making in models is challenging, both in terms of capturing the essence of the processes, and also the way that those behaviours and decisions are or can be represented in the models themselves. In order to advance understanding in this area, a useful first step is to evaluate and start to classify the various types of behaviour and decision making that are required to be modelled. This talk will attempt to set out and provide an initial classification of the different types of behaviour and decision making that a modeller might want to represent in a model. Then, it will be useful to start to assess the main methods of simulation in terms of their capability in representing these various aspects. The three main simulation methods, System Dynamics, Agent Based Modelling and Discrete Event Simulation all achieve this to varying degrees. There is some evidence that all three methods can, within limits, represent the key aspects of the system being modelled. The three simulation approaches are then assessed for their suitability in modelling these various aspects. Illustration of behavioural modelling will be provided from cases in supply chain management, evacuation modelling and rail disruption.

Human brain slices for epilepsy research:pitfalls, solutions and future challenges

Increasingly, neuroscientists are taking the opportunity to use live human tissue obtained from elective neurosurgical procedures for electrophysiological studies in vitro. Access to this valuable resource permits unique studies into the network dynamics that contribute to the generation of pathological electrical activity in the human epileptic brain. Whilst this approach has provided insights into the mechanistic features of electrophysiological patterns associated with human epilepsy, it is not without technical and methodological challenges. This review outlines the main difficulties associated with working with epileptic human brain slices from the point of collection, through the stages of preparation, storage and recording. Moreover, it outlines the limitations, in terms of the nature of epileptic activity that can be observed in such tissue, in particular, the rarity of spontaneous ictal discharges, we discuss manipulations that can be utilised to induce such activity. In addition to discussing conventional electrophysiological techniques that are routinely employed in epileptic human brain slices, we review how imaging and multielectrode array recordings could provide novel insights into the network dynamics of human epileptogenesis. Acute studies in human brain slices are ultimately limited by the lifetime of the tissue so overcoming this issue provides increased opportunity for information gain. We review the literature with respect to organotypic culture techniques that may hold the key to prolonging the viability of this material. A combination of long-term culture techniques, viral transduction approaches and electrophysiology in human brain slices promotes the possibility of large scale monitoring and manipulation of neuronal activity in epileptic microcircuits.

Human resource management in China and India

The first decade of the twenty-first century has witnessed further growth in emerging markets, which is significantly influencing the global economic landscape. For the first time in almost two hundred years, it is in this decade that the emerging economies have caught up with, and raced ahead of, the developed ones in terms of gross domestic product. This is a trend that is likely to continue for some time as many of the developed economies struggle to recover from the global financial crisis. In particular, China and India as two fast growing economies are significantly contributing to the world economic growth and are the flag bearers of this transformation. Acknowledged as favourite destinations for global manufacturing (China) and services (India) related outsourcing, both nations offer huge growth opportunities in most products and services. However, in order to sustain their phenomenal economic growth of the past decades, both countries are facing a number of challenges to their human resource management (HRM). From a macro perspective, these issues tend to appear similar (e.g., attraction and retention of talent), but given the significant sociocultural, institutional, political, legal and other differences between the two nations, the logics underpinning the approaches to managing human resources issues appear somewhat different. This chapter therefore aims to highlight the key forces determining the nature of HRM in China and India. The chapter consists of three main sections, in addition to the Introduction and Conclusions.

Using an in vitro human airway model to study the toxic effects of components of e-cigarettes

Cigarette smoke is a complex mixture of more than 4000 hazardous chemicals including the carcinogenic benzopyrenes. Nicotine, the most potent component of tobacco, is responsible for the addictive nature of cigarettes and is a major component of e-cigarette cartridges. Our study aims to investigate the toxicity of nicotine with special emphasis on the replacement of animals. Furthermore, we intend to study the effect of nicotine, cigarette smoke and e-cigarette vapours on human airways. In our current work, the BEAS 2B human bronchial epithelial cell line was used to analyse the effect of nicotine in isolation, on cell viability. Concentrations of nicotine from 1.1µM to 75µM were added to 5x105 cells per well in a 96 well plate and incubated for 24 hours. Cell titre blue results showed that all the nicotine treated cells were more metabolically active than the control wells (cells alone). These data indicate that, under these conditions, nicotine does not affect cell viability and in fact, suggests that there is a stimulatory effect of nicotine on metabolism. We are now furthering this finding by investigating the pro-inflammatory response of these cells to nicotine by measuring cytokine secretion via ELISA. Further work includes analysing nicotine exposure at different time points and on other epithelial cells lines like Calu-3.