Photochemical delivery of nitric oxide.

There remains considerable interest in developing methods for the targeted delivery of nitric oxide and other small molecule bioregulators such as carbon monoxide to physiological targets. One such strategy is to use a "caged" NO that is "uncaged" by excitation with light. Such photochemical methods convey certain key advantages such as the ability to control the timing, location and dosage of delivery, but also have some important disadvantages, such as the relatively poor penetration of the ultraviolet and visible wavelengths often necessary for the uncaging process. Presented here is an overview of ongoing studies in the author's laboratory exploring new photochemical NO precursors including those with nanomaterial antennas designed to enhance the effectiveness of these precursors with longer excitation wavelengths

The e-revolution and post-compulsory education: using e-business models to deliver quality education

The best practices of e-business are revolutionising not just technology itself but the whole process through which services are provided; and from which important lessons can be learnt by post-compulsory educational institutions. This book aims to move debates about ICT and higher education beyond a simple focus on e-learning by considering the provision of post-compulsory education as a whole. It considers what we mean by e-business, why e-business approaches are relevant to universities and colleges and the key issues this raises for post-secondary education

ERP analysis of cognitive sequencing : a left-anterior negativity related to structural transformation processing

A major objective of cognitive neuroscience is to identify those neurocomputational processes that may be shared by multiple cognitive functions vs those that are highly specifc. This problem of identifying general vs specialized functions is of particular interest in the domain of language processing. Within this domain, event related brain potential (ERP) studies have demonstrated a left anterior negativity (LAN) in a range 300 to 700 ms, associated with syntactic processing, often linked to grammatical function words. These words have little or no semantic content, but rather play a role in encoding syntactic structure required for parsing. In the current study we test the hypothesis that the LAN reflects the operation of a more general sequence processing capability in which special symbols encode structural information that, when combined with past elements in the sequence, allows the prediction of successor elements. We recorded ERPs during a non-linguistic sequencing task that required subjects (nà10) to process special symbols possessing the functional property defined above. When compared to ERPs in a control condition, function symbol processing elicits a left anterior negative shift between with temporal and spatial characteristics quite similar to the LAN described during function word processing in language, supporting our hypothesis. These results are discussed in the context of related studies of syntactic and cognitive sequence processing

Developmental Stages of Perception and Language Acquisition in a Perceptually Grounded Robot

The objective of this research is to develop a system for language learning based on a minimum of pre-wired language-specific functionality, that is compatible with observations of perceptual and language capabilities in the human developmental trajectory. In the proposed system, meaning (in terms of descriptions of events and spatial relations) is extracted from video images based on detection of position, motion, physical contact and their parameters. Mapping of sentence form to meaning is performed by learning grammatical constructions that are retrieved from a construction inventory based on the constellation of closed class items uniquely identifying the target sentence structure. The resulting system displays robust acquisition behavior that reproduces certain observations from developmental studies, with very modest “innate” language specificity

The growing challenge: a strategic review of HIV social care, support and information services across the UK.

This report appears 10 years after the widespread introduction of anti-retroviral therapies. Availability of effective HIV treatment has transformed the UK epidemic, producing a dramatic reduction in mortality and, for many people living with HIV, an increase in health and well-being. Yet, in spite of medical advances, many services seem to continue to follow a historical pattern. Against this background we commissioned Sigma Research to review service commissioning in the HIV sector in order to inform members’ future grant making strategies. Results in the report indicate that commissioners and providers of services believe that people from ethnic minority backgrounds, migrants, children, carers and people from different age groups have unmet needs. Other findings in this research indicate that many more services have been commissioned recently for Africans, on the basis that Africans make up a significant part of the current UK epidemic. We believe this is a valid focus but are discouraged by the approach to these varied communities as one homogenous population. It seems timely to ask whether configuring services to follow broad epidemiological categories without any further refinement is sufficient. The report further suggests that commissioners and providers believe the needs of gay men are well met. This is a surprise and does not accord with the views and experiences of many gay men living with the virus. A significant minority of HIV positive people are neither gay men nor Africans. Even within these two groups the experience of living with HIV varies by age, geographical location and length of infection. HIV positive individuals may look at their needs from another starting point – for example, as a woman or an injecting drug user. The picture appears to be, increasingly, one of fragmentation and isolation. This poses the question: do we have the service models to meet the needs of HIV positive people in the third decade of the epidemic? The report further shows that many of the problems with access to services – including housing and welfare rights – are structural problems, present across health and social care, and are not unique to HIV. HIV support services are funded from budgets which must also contain the increasing costs of anti-retroviral drugs and other medical interventions, and which are therefore subject to continuous attrition and dissaggregation. Also highlighted is the lack of needs-based planning, the diminishing levels of knowledge and expertise among commissioners and the lack of a national strategic vision. In view of the fact that the Government has established a cross-departmental task force to address the epidemic in developing countries this lack of a national strategic vision is lamentable and has the effect of keeping the issue off the political agenda and almost invisible within local funding priorities. This is a concern both to us as funders and to agencies working within the HIV voluntary sector

Thiyl radicals are co-products of dinitrosyl iron complex (DNIC) formation.

Thiyl radicals are detected by EPR as co-products of dinitrosyl iron complex (DNIC) formation. In demonstrating that DNIC formation generates RS˙ in a NO rich environment, these results provide a novel route for S-nitroso thiol formation

From curiosity to applications. A personal perspective on inorganic photochemistry

Over the past several decades, the photochemistry and photophysics of transition metal compounds has blossomed from a relatively niche topic to a major research theme. Applications arising from the elucidation of the fundamental principles defining this field now range from probing the rates and mechanisms of small molecules with metalloproteins to light activated molecular machines. Offered here is a personal perspective of metal complex photochemistry drawn from this author's long involvement with this field. Several examples are described. Topics include characterizing key excited states and tuning these to modify chemical reactivity and/or photoluminescence properties, as well as using photoreactions as an entry to reactive intermediates relevant to homogeneous catalysts. This is followed by discussions of applying these concepts to developing precursors and precursor-antenna conjugates for the photochemical delivery of small molecule bioregulators to physiological targets

Catabolism of cholesterol to bile salts by rat hepatocytes maintained in monolayers

The liver plays a central role in the metabolism of cholesterol being the major site at which lipoproteins are both assembled and degraded and the only organ where cholesterol can be degraded to bile salts. The synthesis of bile salts by the liver provides the major pathway for the removal of cholesterol from the body.The results in this thesis describe the characterisation of a rat hepatocyte monolayer system, suitable for studying the synthesis of bile salts. The utilization of the cholesterol derived from a high density lipoprotein subfraction (HDL2) for the synthesis of bile salts was also investigated.Following the isolation of a viable cell preparation, hepatocytes were maintained in monolayers for up to 24h. During this period hepatocytes were shown to maintain their viability and to synthesise and secrete bile salts, as determined by radioimmunoassay of conjugated cholic, chenodeoxycholic and ß-muricholic acids. The rate of synthesis of these bile salts by hepatocytes was increased by feeding rats cholestyramine for at least 5 days prior to the preparation of hepatocyte monolayers.Incubation of hepatocyte monolayers with rat HDL2 had no effect on the synthesis of the three bile acid conjugates measured when the cells were obtained from rats fed the pellet diet. However, when the experiment was repeated using hepatocytes obtained from rats fed cholestyramine, HDL2 was found to increase the synthesis of the bile salts measured. This is the first report that a defined lipoprotein fraction can increase the synthesis of bile salts.In an attempt to ascertain the reason for the increase in the synthesis of bile salts, hepatocytes isolated from cholestyramine- vi fed rats were incubated in the presence of HDL2 radiolabelled with either [4- 14Clcholesterol or [4- 14C]cholesteryl oleate. The degradation of the radiolabelled HDL2-cholesterol to bile salts was subsequently determined. The results indicated that the increase in the synthesis of bile salts was due to the utilization of HDL2-cholesteryl ester.Finally, the effect of HDL2 on the synthesis of cholesterol and the utilization of newly synthesised cholesterol for the synthesis of bile salts in hepatocyte monolayers was determined. The results showed that HDL2 had no effect on either cholesterol synthesis or the utilization of newly synthesised cholesterol for the synthesis of bile salts