Improving the function of islet and beta-cell grafts

Background: Human islet transplantation would offer a less invasive and more physiological alternative than whole pancreas transplantation and insulin injections respectively for the treatment of diabetes mellitus if islet graft survival can be improved. Initial recipient post-transplant insulin independence declines to <10% after 5 years. Factors contributing to graft failure include enzymatic disruption of the islet microenvironment during isolation, diabetogenic effects of immunosuppressants and metabolic stress resulting from slow revascularisation. Aims: To investigate the effect of co-culture in both static (SC) and rotational culture (RC) of BRINBDII beta-cells (Dl1) and human umbilical vein endothelial cells (HUVEC) on Dl1 insulin secretion; and the effect of a thiazolidinedione (TZD) on DII function and HUVEC proliferation. To assess the effect of culture media, SC, RC and a TZD on human islet morphology, insulin secretion and VEGF production. To initiate in vivo protocol development for assessment of revascularisation of human islet grafts. Methods: D11 cells were cultured +/-TZD and co-cultured with HUVEC +/-TZD in SC and RC. Dl1 insulin secretion was induced by static incubation with low glucose (1.67mM), high glucose (l6.7mM: and high glucose with 10mM theophylline (G+T) and determined by ELISA. HUVEC were cultured +/-TZD in SC and RC and proliferation was assessed by ATP luminescence assay and VEGF ELISA. D II and HUVEC morphology was determined by immunocytochemistry. Human islets were cultured in SC and RC in various media +/-TZD. Insulin secretion was determined as above and VEGF production by fluorescence immunocytochemistry (FI) and ELISA. Revascularisation of islet grafts was assessed by vascular corrosion cast and FI. Results: Dll cultures showed significantly increased insulin secretion in response to 16.7mM and G+T over basal; this was enhanced by RC and further improved by adding 10mM TZD. Untreated Dll/HUVEC co-cultures displayed significantly increased insulin secretion in response to 16.7mM and G+T over basal, again enhanced by RC and improved with 10mM TZD. 10mM TZD significantly increased HUVEC proliferation over control. Human islets maintained in medium 199 (mI99) in SC and RC exhibited comparable maintenance of morphology and insulin secretory profiles compared to islets maintained in RPMI, endothelial growth media and dedicated islet medium Miami# I. All cultures showed significantly increased insulin secretion in response to 16.7mM and G+T over basal; this was enhanced by RC and in certain instances further improved by adding 25mM TZD. TZD increased VEGF production and release as determined by ELISA. Post-implant vascular corrosion casts of mouse kidneys analysed by x-ray micro tomography indicates a possible TZD enhancement of microvessel growth via VEGF upregulation. Conclusions: D II /HUVEC co-culture in SC or RC does not alter the morphology of either cell type and supports D 11 function. TZD improves 0 I I and D I I/HUVEC SC and RC co-culture insulin secretion while increasing HUVEC proliferation. Human islet RC supports islet functional viability and structural integrity compared to SC while the addition of TZD occasionally further improves secretagogue induced insulin secretion. Expensive, 'dedicated' islet media showed no advantage over ml99 in terms of maintaining islet morphology or function. TZD upregulates VEGF in islets as shown by ELISA and suggested by x-ray micro tomography analysis of vascular corrosion casts. Maintenance of islets in RC and treatment with TZD prior to transplant may improve the functional viability and revascularisation rate of islet grafts.

Using QFD for e-business planning and analysis in a micro-sized enterprise

Purpose - The purpose of this paper is to show how QFD can be used as part of a structured planning and analysis framework for micro-sized enterprises to build-up their e-business capabilities. Design/methodology/approach - This case study has been produced using a new framework which integrates the balanced scorecard, value chain and quality function deployment techniques into an integrated framework known as the E-Business Planning and Analysis Framework (E-PAF). It has been produced using an action research approach. Findings - A new framework with a supporting case study is provided. This case study has demonstrated that the framework can be applied successfully to micro-sized enterprises (those with less than ten employees) to successfully plan new strategic and technical developments. This will enhance the online service that the company is able to provide. Research limitations/implications - This paper presents a single case study. The technical recommendations are currently being implemented. Originality/value - Such analytical techniques are most commonly associated with large organisations, and are not specifically associated with e-business planning. This paper provides a new framework that will be of general applicability to other similarly sized enterprises that are looking to improve e-business capabilities. © Emerald Group Publishing Limited.

Spatial topography of the neurofibrillary tangles in cortical and subcortical regions in progressive supranuclear palsy

Objective: To study the topography of neurofibrillary tangles (NFT) in cortical and subcortical areas in progressive supranuclear palsy (PSP). Methods: Pattern analysis was carried out on tau-positive NFT in eight PSP cases. Results: Of the areas studied, NFT were randomly distributed in 68%, regularly distributed in 3%, and clustered in 29%. A regular distribution of clusters was more frequent in cortical than subcortical areas. Conclusion: NFT topography in subcortical areas was similar to inclusions in the synucleinopathy multiple system atrophy (MSA) but in cortical areas was comparable to other tauopathies. © 2006 Elsevier Ltd. All rights reserved.

The influence of social e-atmospherics in practice:a website content analysis perspectives from Turkey as an illustration of emerging market and France as a mature market

E-atmospherics have been often analyzed in terms of functional features, leaving its characteristics' link to social capital co-creation as a fertile research area. Prior research have demonstrated the capacity of e-atmospherics' at modifying shopping habits towards deeper engagement. Little is known on how processes and cues emerging from the social aspects of lifestyle influence purchasing behavior. The anatomy of social dimension and ICT is the focus of this research, where attention is devoted to unpack the meanings and type of online mundane social capital creation. Taking a cross-product/services approach to better investigate social construction impact, our approach also involves both an emerging and a mature market where exploratory content analysis of landing page are done on Turkish and French web sites, respectively. We contend that by comprehending social capital, daily micro practices, habits and routine, a better and deeper understanding on e-atmospherics incumbent and potential effects on its multi-national e-customer will be acquired.

An investigation of thin amorphous carbon-based sputtered coatings for MEMS and micro-engineering applications

The work presented in this thesis describes an investigation into the production and properties of thin amorphous C films, with and without Cr doping, as a low wear / friction coating applicable to MEMS and other micro- and nano-engineering applications. Firstly, an assessment was made of the available testing techniques. Secondly, the optimised test methods were applied to a series of sputtered films of thickness 10 - 2000 nm in order to: (i) investigate the effect of thickness on the properties of coatingslcoating process (ii) investigate fundamental tribology at the nano-scale and (iii) provide a starting point for nanotribological coating optimisation at ultra low thickness. The use of XPS was investigated for the determination of Sp3/Sp2 carbon bonding. Under C 1s peak analysis, significant errors were identified and this was attributed to the absence of sufficient instrument resolution to guide the component peak structure (even with a high resolution instrument). A simple peak width analysis and correlation work with C KLL D value confirmed the errors. The use of XPS for Sp3/Sp2 was therefore limited to initial tentative estimations. Nanoindentation was shown to provide consistent hardness and reduced modulus results with depth (to < 7nm) when replicate data was suitably statistically processed. No significant pile-up or cracking of the films was identified under nanoindentation. Nanowear experimentation by multiple nanoscratching provided some useful information, however the conditions of test were very different to those expect for MEMS and micro- / nano-engineering systems. A novel 'sample oscillated nanoindentation' system was developed for testing nanowear under more relevant conditions. The films were produced in an industrial production coating line. In order to maximise the available information and to take account of uncontrolled process variation a statistical design of experiment procedure was used to investigate the effect of four key process control parameters. Cr doping was the most significant control parameter at all thicknesses tested and produced a softening effect and thus increased nanowear. Substrate bias voltage was also a significant parameter and produced hardening and a wear reducing effect at all thicknesses tested. The use of a Cr adhesion layer produced beneficial results at 150 nm thickness, but was ineffective at 50 nm. Argon flow to the coating chamber produced a complex effect. All effects reduced significantly with reducing film thickness. Classic fretting wear was produced at low amplitude under nanowear testing. Reciprocating sliding was produced at higher amplitude which generated three body abrasive wear and this was generally consistent with the Archard model. Specific wear rates were very low (typically 10-16 - 10-18 m3N-1m-1). Wear rates reduced exponentially with reduced film thickness and below (approx.) 20 nm, thickness was identified as the most important control of wear.

Chronotopographical analysis of the pattern onset visual evoked magnetic response (VEMR):Implications for waveform peak identification

The topography of the visual evoked magnetic response (VEMR) to a pattern onset stimulus was studied in five normal subjects using a single channel BTi magnetometer. Topographic distributions were analysed at regular intervals following stimulus onset (chronotopograpby). Two distinct field distributions were observed with half field stimulation: (1) activity corresponding to the C11 m which remains stable for an average of 34 msec and (2) activity corresponding to the C111 m which remains stable for about 50 msec. However, the full field topography of the largest peak within the first 130 msec does not have a predictable latency or topography in different subjects. The data suggest that the appearance of this peak is dependent on the amplitude, latency and duration of the half field C11 m peaks and the efficiency of half field summation. Hence, topographic mapping is essential to correctly identify the C11 m peak in a full field response as waveform morphology, peak latency and polarity are not reliable indicators. © 1993.

Precise orbit determination and analysis from satellite altimetry and laser ranging

For optimum utilization of satellite-borne instrumentation, it is necessary to know precisely the orbital position of the spacecraft. The aim of this thesis is therefore two-fold - firstly to derive precise orbits with particular emphasis placed on the altimetric satellite SEASAT and secondly, to utilize the precise orbits, to improve upon atmospheric density determinations for satellite drag modelling purposes. Part one of the thesis, on precise orbit determinations, is particularly concerned with the tracking data - satellite laser ranging, altimetry and crossover height differences - and how this data can be used to analyse errors in the orbit, the geoid and sea-surface topography. The outcome of this analysis is the determination of a low degree and order model for sea surface topography. Part two, on the other hand, mainly concentrates on using the laser data to analyse and improve upon current atmospheric density models. In particular, the modelling of density changes associated with geomagnetic disturbances comes under scrutiny in this section. By introducing persistence modelling of a geomagnetic event and solving for certain geomagnetic parameters, a new density model is derived which performs significantly better than the state-of-the-art models over periods of severe geomagnetic storms at SEASAT heights. This is independently verified by application of the derived model to STARLETTE orbit determinations.

A sociological analysis of four police consultative committees in Birmingham

Consultation between the police and the community was a recommendation of Lord Scarman in his report into the Brixton riots in 1981. By 1982 the West Midlands Police Authority had established local consultative committees on each police sub-division. This thesis is a study of four Police Consultative Committees in Birmingham, using qualitative methods of attendance at committee meetings and interviews with committee members. The research was carried out between 1990 and 1992 - ten years after formal consultation was established, and aimed to examine the relationship between the micro social processes of the committees and key sociological theoretical concepts. The analysis of the four committees contextualises them within the social and political parameters of urban policing in the late 1980s. Each committee is taken as a case study to highlight the following aspects of consultation:- relations between the police and black communities; membership, representation and accountability; responding to community conflict; crime prevention agencies and networks of social control. The findings are then generalised to the sociological theoretical concepts of hegemony, legitimation, community conflict and social control. The central proposition of this thesis is that, whilst these committees are not fulfilling the role Lord Scarman envisaged for them (of involving local community representatives in policing strategies and policies), they do have important policing and political roles. It is argued that they offer a platform from which senior police officers can engage local people into supporting policing objectives without actually involving them in determining those objectives. Furthermore, such committees have political symbolism in that they enable the government to be seen to be responding to the issues of accountability and relations between the police and black communities following the urban disorders, without actually devolving any statutory powers to the community.

Elastic-plastic analysis of complete building structures

In this Thesis, details of a proposed method for the elastic-plastic failure load analysis of complete building structures are given. In order to handle the problem, a computer programme in Atlas Autocode is produced. The structures consist of a number of parallel shear walls and intermediate frames connected by floor slabs. The results of an experimental investigation are given to verify the theoretical results and to demonstrate various factors that may influence the behaviour of these structures. Large full scale practical structures are also analysed by the proposed method and suggestions are made for achieving design economy as well as for extending research in various aspects of this field. The existing programme for elastic-plastic analysis of large frames is modified to allow for the effect of composite action of structural members, i.e. reinforced concrete floor slabs and the supporting steel beams. This modified programme is used to analyse some framed type structures with composite action as well as those which incorporate plates and shear walls. The results obtained are studied to ascertain the influence of composite action and other factors on the load carrying capacity of both bare frames and complete building structures. The theoretical failure load presented in this thesis does not predict the overall failure load of the structure nor does it predict the partial failure load of the shear walls and slabs but it merely predicts the partial failure load of a single frame and assumes that the loss of stiffess of such a frame renders the overall structure unusable. For most structures the analysis proposed in this thesis is likely to break down prematurely due to the failure of the slab and shear wall system and this factor must be taken into account in any future work on such structures. The experimental work reported in this thesis is acknowledged to be unsatisfactory as a verification of the limited theory proposed. In particular perspex was not found to be a suitable material for testing at high loads, micro-concrete may be more suitable.

Police interviews with women reporting rape: a critical discourse analysis

This study investigates the discursive patterns of interactions between police interviewers and women reporting rape in significant witness interviews. Data in the form of video recorded interviews were obtained from a UK police force for the purposes of this study. The data are analysed using a multi-method approach, incorporating tools from micro-sociology, Conversation Analysis and Discursive Psychology, to reveal patterns of interactional control, negotiation, and interpretation. The study adopts a critical approach, which is to say that as well as describing discursive patterns, it explains them in light of the discourse processes involved in the production and consumption of police interview talk, and comments on the relationship between these discourse processes and the social context in which they occur. A central focus of the study is how interviewers draw on particular interactional resources to shape interviewees? accounts in particular ways, and this is discussed in relation to the institutional role of the significant witness interview. The discussion is also extended to the ways in which mainstream rape ideology is both reflected in, and maintained by, the discursive choices of participants. The findings of this study indicate that there are a number of issues to be addressed in terms of the training currently offered to officers at Level 2 of the Professionalising Investigation Programme (PIP) (NPIA, 2009) who intend to conduct significant witness interviews. Furthermore, a need is identified to bring the linguistic and discursive processes of negotiation and transformation identified by the study to the attention of the justice system as a whole. This is a particularly pressing need in light of judicial reluctance to replace written witness statements, the current „end product? of significant witness interviews, with the video recorded interview in place of direct examination in cases of rape.

A penny for your thoughts! Patterns of fMRI activity reveal the content and the spatial topography of visual mental images

Visual mental imagery is a complex process that may be influenced by the content of mental images. Neuropsychological evidence from patients with hemineglect suggests that in the imagery domain environments and objects may be represented separately and may be selectively affected by brain lesions. In the present study, we used functional magnetic resonance imaging (fMRI) to assess the possibility of neural segregation among mental images depicting parts of an object, of an environment (imagined from a first-person perspective), and of a geographical map, using both a mass univariate and a multivariate approach. Data show that different brain areas are involved in different types of mental images. Imagining an environment relies mainly on regions known to be involved in navigational skills, such as the retrosplenial complex and parahippocampal gyrus, whereas imagining a geographical map mainly requires activation of the left angular gyrus, known to be involved in the representation of categorical relations. Imagining a familiar object mainly requires activation of parietal areas involved in visual space analysis in both the imagery and the perceptual domain. We also found that the pattern of activity in most of these areas specifically codes for the spatial arrangement of the parts of the mental image. Our results clearly demonstrate a functional neural segregation for different contents of mental images and suggest that visuospatial information is coded by different patterns of activity in brain areas involved in visual mental imagery. Hum Brain Mapp 36:945-958, 2015.

Rationality as a barrier to peace:micro-evidence from Kosovo

Despite a significant expansion of the literature on conflicts and fragility of states, only a few systematic attempts have been made to link the theoretical literature on social conflicts to the available micro-level information about the people who are involved in these conflicts. We address this lacuna in the literature using a household-level data set from Kosovo. Our analysis suggests that it is individually rational for competing ethnic communities, Kosovar Albanians and Kosovar Serbs, to resist a quick agreement on a social contract to share the region's resources.

A comparative analysis of cultural value orientations of Polish and Turkish employees:implications for international human resource management

This study empirically compares and contrasts the cultural value orientations of employees from Poland and Turkey by testing the compatibility of their values in three stages through seven cultural dimensions. The first phase of the study deals with the assessment of inter-country cultural value differences; the second phase investigates the intra-country cultural dynamics between selected demographic groups; and the third phase examines the inter-country cultural differences among the selected demographic groups of employees. The research has been conducted adopting the Maznevski, DiStephano, and Nason's (1995) version of cultural perspectives questionnaire with a sample of 744 (548 Polish and 196 Turkish) respondents. The results show significant cultural differences between Poland and Turkey, a presence of cultural dynamics among certain demographic groups within the country, and a mixture of convergence and divergence in the value systems of certain demographic groups both within and between the two nation(s). The research findings convey important messages to international human resource strategists in order for them to employ an effective and rational employment policy and business negotiation approach(es) to effectively operate in these countries. It also highlights that diversity of cultural values not only requires viewing each of them through cultural dimensions at a macro-level with a cross-country reference, but also requires monitoring their dynamics at the micro-level with reference to controlled demographic groups. © 2013 Taylor & Francis.