Computational Mechanistic and Stereochemical Studies of Single-Site Polymerisation Catalysts and Reactions

Computational investigations into four metal-centred polymerisation catalysts are presented. The work investigates how and why the catalysts behave as they do, focusing on specific interactions within the catalyst structure itself and also on the transition states involved in the polymerisation reactions. Density functional theory has been used to examine the effect of the metal, the role of the ligand and the interplay between the two. Each study addresses particular mechanistic and structural questions that have been raised during experimental investigations and that are difficult to answer experimentally. Chapter one provides a general overview of computational techniques used in chemical modelling. The specific methods used in this work are presented as well as a brief review of modern trends. Chapter two investigates an unusual pair of metal-hydrogen interactions in a tin bis(triazenide) complex. We have termed this double M-H interaction “bifurcated” and compared other systems in which this interaction is present (and often unidentified). A variety of computational techniques are used to analyse the nature of the interactions both in qualitative and quantitative terms. The third chapter investigates the mechanism of alkyl transfer in a magnesium bis(imino)pyridine complex. A number of mechanistic pathways are explored to explain the original report of non-electrophilic alkylation at a pyridine nitrogen. We consider in particular how the solvent and the role of other species in the reaction mixture may influence the mechanism. Chapter four describes the inversion of configuration occurring in a pseudo-C3- symmetric zirconium tris(phenolate) complex. Variable temperature NMR spectra and simulations complement DFT calculations to explore the mechanism of inversion. We question the long-held assumption that the inversion process is concerted. In chapter five, the polymerisation of rac-lactide by an aluminium salen-type system is investigated in detail through characterisation of the transition state structures. Specifically, we have aimed to explain the different behaviour of two structurally similar catalytic species’ which produce polymer of different tacticity. Application of a variety of additional computational techniques in a number of these studies supplements the density functional calculations. They provide insight into specific interactions in both starting materials and transition states and detailed information about the reaction mechanisms

Modelling the effects of space weather at the Earth’s surface : a UK geoelectric field model

Geomagnetically Induced Currents (GIC), which can flow in technological systems such as power transmission grids, are a consequence of the geoelectric field induced at the surface of the Earth during geomagnetic storms. This poster describes the development of a new 3D 'Thin-Sheet' geoelectric field model which covers the whole of the UK and includes the influence of the surrounding shelf seas. The model can be used to compute the response of the geoelectric field to geomagnetic storms. In conjunction with a power grid model this enables us to estimate GIC flow in power networks. As an example, we consider the major geomagnetic storm of October 2003. It is envisaged that the model will form one component of a near real time GIC warning package which is currently being developed by the British Geological Survey (BGS) in conjunction with Scottish Power Plc. The magnetic field associated with the induced geoelectric field is easily calculated. Thus, the electric field model may also be of interest to those studying the effect of internal (induced) geomagnetic field signals on the total measured geomagnetic field

Linking genetics with biology in disease research: an interview with Nick Hastie

Professor Nick Hastie is Director of the MRC Human Genetics Unit in Edinburgh, a centre originally famous for early studies of chromosome biology. He is also Director of the newly formed Institute of Genetics and Molecular Medicine, which includes the Human Genetics Unit. In addition to overseeing the work on cancer and developmental genetics in his own lab, he is involved in a number of large-scale genetic studies aimed at uncovering genetic risk factors for various human diseases

Specimens as research objects: reconciliation across distributed repositories to enable metadata propagation

Botanical specimens are shared as long-term consultable research objects in a global network of specimen repositories. Multiple specimens are generated from a shared field collection event; generated specimens are then managed individually in separate repositories and independently augmented with research and management metadata which could be propagated to their duplicate peers. Establishing a data-derived network for metadata propagation will enable the reconciliation of closely related specimens which are currently dispersed, unconnected and managed independently. Following a data mining exercise applied to an aggregated dataset of 19,827,998 specimen records from 292 separate specimen repositories, 36% or 7,102,710 specimens are assessed to participate in duplication relationships, allowing the propagation of metadata among the participants in these relationships, totalling: 93,044 type citations, 1,121,865 georeferences, 1,097,168 images and 2,191,179 scientific name determinations. The results enable the creation of networks to identify which repositories could work in collaboration. Some classes of annotation (particularly those regarding scientific name determinations) represent units of scientific work: appropriate management of this data would allow the accumulation of scholarly credit to individual researchers: potential further work in this area is discussed.Comment: 9 pages, 1 table, 3 figure

Local production of medical technologies and its effect on access in low and middle income countries: a systematic review of the literature

Objectives: The objective of this study was to assess the existing theoretical and empirical literature examining the link between "local production" of pharmaceuticals and medical devices and increased local access to these products. Our preliminary hypothesis is that studies showing a robust relationship between local production and access to medical products are sparse, at best. Methods: An extensive literature search was conducted using a wide variety of databases and search terms intending to capture as many different aspects of this issue as possible. The results of the search were reviewed and categorized according to their relevance to the research question. The literature was also reviewed to determine the rigor used to examine the effects of local production and what implications these experiences hold for other developing countries. Results: Literature addressing the benefits of local production and the link between it and access to medical products is sparse, mainly descriptive and lacking empirical evidence. Of the literature we reviewed that addressed comparative economics and strategic planning of multinational and domestic firms, there are few dealing with emerging markets and lower-middle income countries and even fewer that compare local biomedical producers with multinational corporations in terms of a reasonable metric. What comparisons exist mainly relate to prices of local versus foreign/multinational produced medicines. Conclusions: An assessment of the existing theoretical and empirical literature examining the link between "local production" of pharmaceuticals and medical devices and increased local access to these products reveals a paucity of literature explicitly dealing with this issue. Of the literature that does exist, methods used to date are insufficient to prove a robust relationship between local production of medical products and access to these products. There are mixed messages from various studies, and although the studies may correctly depict specific situations in specific countries with reference to specific products, such evidence cannot be generalized. Our review strongly supports the need for further research in understanding the dynamic link between local production and access to medical product

Avian Resistance to Campylobacter jejuni Colonization Is Associated with an Intestinal Immunogene Expression Signature Identified by mRNA Sequencing

peer-reviewedThis research was funded by the The Irish Department of Agriculture and Food’s Food Institutional Research Measure (http://www.agriculture.gov.ie/ research/foodinstitutionalresearchmeasurefirm) – Grant No: 06_RDD_486.Campylobacter jejuni is the most common cause of human bacterial gastroenteritis and is associated with several post-infectious manifestations, including onset of the autoimmune neuropathy Guillain-Barré syndrome, causing significant morbidity and mortality. Poorly-cooked chicken meat is the most frequent source of infection as C. jejuni colonizes the avian intestine in a commensal relationship. However, not all chickens are equally colonized and resistance seems to be genetically determined. We hypothesize that differences in immune response may contribute to variation in colonization levels between susceptible and resistant birds. Using high-throughput sequencing in an avian infection model, we investigate gene expression associated with resistance or susceptibility to colonization of the gastrointestinal tract with C. jejuni and find that gut related immune mechanisms are critical for regulating colonization. Amongst a single population of 300 4-week old chickens, there was clear segregation in levels of C. jejuni colonization 48 hours post-exposure. RNAseq analysis of caecal tissue from 14 C. jejuni-susceptible and 14 C. jejuni-resistant birds generated over 363 million short mRNA sequences which were investigated to identify 219 differentially expressed genes. Significantly higher expression of genes involved in the innate immune response, cytokine signaling, B cell and T cell activation and immunoglobulin production, as well as the renin-angiotensin system was observed in resistant birds, suggesting an early active immune response to C. jejuni. Lower expression of these genes in colonized birds suggests suppression or inhibition of a clearing immune response thus facilitating commensal colonization and generating vectors for zoonotic transmission. This study describes biological processes regulating C. jejuni colonization of the avian intestine and gives insight into the differential immune mechanisms incited in response to commensal bacteria in general within vertebrate populations. The results reported here illustrate how an exaggerated immune response may be elicited in a subset of the population, which alters host-microbe interactions and inhibits the commensal state, therefore having wider relevance with regard to inflammatory and autoimmune disease

Multiculture and public parks : researching super-diversity and attachment in public green spaces

Situating itself in encounter and public space debates and borrowing from non-representational theory approaches this paper uses data from the authors’ two-year ESRC research project to consider how local urban parks can work as sites of routine encounter, mixity and place belonging. The paper explores how parks as green public spaces are not only important as sites of inclusive openness but that the materiality of parks is a key dynamic in affective encounter processes. Parks can work as animators of social interactions, participatory practices and place affinities across ethnic and cultural difference. The paper concludes that the concept of convivial encounter can be extended to incorporate the concept of elective practices - choosing to be in shared public space can generate connective sensibilities which are not necessarily contingent on exchange. In using parks as a lens to examine localities and diversity the paper critically reflects on research practices for understanding and describing heterogeneous formations of multiculture and argues that the project’s research design and the fieldwork methods present an attempt to carefully and appropriately respond to research with complexly different places and populations

Conditional expression in corticothalamic efferents reveals a developmental role for nicotinic acetylcholine receptors in modulation of passive avoidance behavior

Prenatal nicotine exposure has been linked to attention deficit hyperactivity disorder and cognitive impairment, but the sites of action for these effects of nicotine are still under investigation. High-affinity nicotinic acetylcholine receptors (nAChRs) contain the .2 subunit and modulate passive avoidance (PA) learning in mice. Using an inducible, tetracycline-regulated transgenic system, we generated lines of mice with expression of high-affinity nicotinic receptors restored in specific neuronal populations. One line of mice shows functional .2 subunit-containing nAChRs localized exclusively in corticothalamic efferents. Functional, presynaptic nAChRs are present in the thalamus of these mice as detected by nicotine-elicited rubidium efflux assays from synaptosomes. Knock-out mice lacking high-affinity nAChRs show elevated baseline PA learning, whereas normal baseline PA behavior is restored in mice with corticothalamic expression of these nAChRs. In contrast, nicotine can enhance PA learning in adult wild-type animals but not in corticothalamic-expressing transgenic mice. When these transgenic mice are treated with doxycycline in adulthood to switch off nAChR expression, baseline PA is maintained even after transgene expression is abolished. These data suggest that high-affinity nAChRs expressed on corticothalamic neurons during development are critical for baseline PA performance and provide a potential neuroanatomical substrate for changes induced by prenatal nicotine exposure leading to long-term behavioral and cognitive deficits