Contributions to our understanding of T cell physiology through unveiling the T cell proteome

Since the sequencing of the human genome was completed, attention has turned to examining the functionality of the molecular machinery, in particular of protein expression. Differential proteome analysis by two-dimensional electrophoresis has been adopted to study changes in T cell proteomes during T cell activation, and this work is increasing our understanding of the complexity of signals elicited across multiple pathways. The purpose of this review is to summarize the available evidence in the application of proteomic techniques and methodologies to understand T cell receptor activation from lipid raft and cytoskeletal rearrangements, through to signalling cascades, transcription factor modulation and changes in protein expression patterns. These include post-translational modifications, which are not encoded by the genome. © 2007 British Society for Immunology.

Managerial perceptions of factors influencing technology management in South Africa

A challenge for developing countries is to become part of the global economy. Their economic well being is dependent on their ability to attain the levels of technological development which could make them globally competitive. Infrastructural and educational problems pose immediate barriers which should be addressed as these countries embark on projects to enhance their technological base. The technology selected should be appropriate for the country's level of development and expertise. The implementation of that technology will place a new set of demands on managers and workers. This paper describes an investigation of perceptions of technology management in South Africa, a country which is developed in certain areas, but which remains desperately poor in other respects. South Africa's politics and history have always confronted managers with unique demands. The paper examines the perceptions of 132 South African managers regarding technology management by studying the relationship between the importance of different factors in managing new technology, and the extent to which a manager can control them. An importance-control grid framework is used to isolate individual parameters and to assess these in relation to the complexity of a manager's environment. The research highlights imbalances between importance and control, and suggests reasons therefor. Some broader implications for managers are also discussed. © 2002 Elsevier Science Ltd. All rights reserved.

Social impact assessment of a sewerage project in Barbados

This report investigates why a nationally important and internationally funded infrastructural project within the Caribbean island of Barbados — The South Coast Sewerage Project — spurned a substantial level of negative socio-economic externalities. Primary and secondary research evaluated the presence or effectiveness of social impact assessment as a mitigation tool. The mitigation measures suggested within the appraisal report appear to have been considered by the Project Execution Unit (PEU) of Government of Barbados. The primary obstacle seems to have been the implementation of the mitigation process by the contractor. This highlights the need to foster an interconnected and symbiotic relationship between appraisal and implementation, if an initiative is to be conducted efficiently and effectively. Additionally, the South Coast Sewerage Project exemplifies the importance of establishing and sustaining a monitoring/control mechanism as an integral part of project construction.

Transforming the eastern neighbourhood: the security implications of European Union Activity in Ukraine 2000-2006

This thesis examines the external activities of the European Union conducted in the wider Europe against the backdrop of eastern enlargement. It focuses on the technical aspects of EU diplomacy, using qualitative research methodology to study the programmes and initiatives launched since the year 2000 in the countries lying along the Union’s new border to the east. Drawing on evidence from Ukraine, it hypothesises that the EU is an agent of transformation in the eastern neighbourhood and that this transformation has important implications for the regional order in the post-Soviet space. The thesis constitutes an investigation into the transformational activities engaged by the EU in Ukraine conducted with an eye to their strategic implications. It documents and analyses three instances of EU intervention in Ukraine’s internal processes that relate to management of cross-border traffic in the Ukrainian-Russian borderland, restructuring of the country’s energy sector, and conduct of its contentious presidential election in 2004. It is argued that while these interventions have explicitly sought to advance the Union’s security with respect to certain twenty-first century transnational threats, they have at the same time served to confer important strategic advantages on the EU that include giving the bloc greater knowledge and control over developments in Ukraine and that contribute to the dismantling of infrastructural, institutional and other ties between Kiev and the other Soviet successor states, notably Russia. The effect of the European Union’s actions in the region, whether intended or not, has thus been to undermine any competing regional initiatives that cut across its own functions, and thereby to assert itself as the primary integration project in Europe. By showing how technical interventions in the politics, economics and administration of Ukraine can yield important geopolitical dividends, this thesis demonstrates that, in the context of EU external relations, high and low politics are interlinked.

Foreign direct investment and corruption

In the last few decades, the world has witnessed an enormous growth in the volume of foreign direct investment (FDI). The global stock of FDI reached US$ 7.5 trillion in 2003 and accounted for 11% of world Gross Domestic Product, up from 7% in 1990. The sales of multinational enterprises at around US$ 19 trillion were more than double the level of world exports. Substantial FDI inflows went into transition countries. Inflows into one of the region's largest recipient, the Russian Federation, almost doubled, enabling Russia to become one of the five top FDI destinations in 2005-2006. FDI inflows in Russia have increased almost threefold from 13.6% in 2003 to 35% in 2007. In 2003, these flows were twice greater than those into China; whilst in 2007 they were six times larger. Russia's FDI inflows were also about 2.5 times greater than those of Brazil. Efficient government institutions are argued by many economists to foster FDI and growth as a result. However, the magnitude of this effect has yet to be measured. This thesis takes a Political Economy approach to explore, empirically, the potential impact of malfunctioning governmental institutions, proxied by three indices of perceived corruption, on FDI stocks accumulation/distribution within Russia over the period of 2002-2004. Using a regional data-set it concentrates on three areas relating to FDI. Firstly, it considers the significance, the size and the sign of the impact of perceived corruption on accumulation of FDI stocks within Russia. Secondly, it quantifies the impact of perceived corruption on the volume of FDI stocks simultaneously estimating the impact of the investment in public capital such as telecommunications and transportation networks on FDI in the presence of corruption. In particular, it addresses the question whether more corrupt regions in Russia are also those that could have accumulated more of FDI stocks, and investigates whether those 'more corrupt' regions would have had lower level of public capital investment. Finally, it examines whether decentralisation increases or decreases corruption and whether a larger extent of decentralisation has a positive or negative impact on FDI (stocks). The results of three studies are as follows. Firstly, along with market potential, corruption is found to be one of the key factors in explaining FDI distribution within Russia between 2002 and 2004. Secondly, corruption on average is found to be related to FDI positively suggesting that it may act as speed money: to save their time foreign direct investors might be willing to bribe the regional authorities so to move in front of the bureaucratic lines. Thirdly, although when corruption is controlled for, the impact of the latter on unobservable FDI is found to be on average positive, no association between FDI and public investment is observed with the only exception of transportation infrastructure (i.e., railway). The results might suggest therefore that it is possible that not only regions with high levels of perceived corruption attract more FDI but also that expansions in public capital investments are not accompanied by an increase of the volume of FDI (stocks) in regions with high levels of corruption. This casts some doubt on the productivity of the investment in public capital in these regions as it might be that bureaucrats may prefer to use these infrastructural projects for rent extraction. Finally, we find decentralisation to have a significant and positive impact on both FDI stock accumulation and corruption, suggesting that local governments may spend more on public goods to make the area more attractive to foreign investors but at the same time they may be interested into extracting rents from foreign investors. These results support the idea that the regulation of FDI is associated with and facilitated by a larger public sector, which distorts competition and introduces opportunities for rent-seeking by particular economic and political factors.

Physiological effects of oxidized phospholipids and their cellular signaling mechanisms in inflammation

Oxidized phospholipids, such as the products of the oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine by nonenzymatic radical attack, are known to be formed in a number of inflammatory diseases. Interest in the bioactivity and signaling functions of these compounds has increased enormously, with many studies using cultured immortalized and primary cells, tissues, and animals to understand their roles in disease pathology. Initially, oxidized phospholipids were viewed largely as culprits, in line with observations that they have proinflammatory effects, enhancing inflammatory cytokine production, cell adhesion and migration, proliferation, apoptosis, and necrosis, especially in vascular endothelial cells, macrophages, and smooth muscle cells. However, evidence has emerged that these compounds also have protective effects in some situations and cell types; a notable example is their ability to interfere with signaling by certain Toll-like receptors (TLRs) induced by microbial products that normally leads to inflammation. They also have protective effects via the stimulation of small GTPases and induce up-regulation of antioxidant enzymes and cytoskeletal rearrangements that improve endothelial barrier function. Oxidized phospholipids interact with several cellular receptors, including scavenger receptors, platelet-activating factor receptors, peroxisome proliferator-activated receptors, and TLRs. The various and sometimes contradictory effects that have been observed for oxidized phospholipids depend on their concentration, their specific structure, and the cell type investigated. Nevertheless, the underlying molecular mechanisms by which oxidized phospholipids exert their effects in various pathologies are similar. Although our understanding of the actions and mechanisms of these mediators has advanced substantially, many questions do remain about their precise interactions with components of cell signaling pathways.

Hsc70-induced changes in clathrin-auxilin cage structure suggest a role for clathrin light chains in cage disassembly

The molecular chaperone, Hsc70, together with its cofactor, auxilin, facilitates the ATP-dependent removal of clathrin during clathrin-mediated endocytosis in cells. We have used cryo-electron microscopy to determine the 3D structure of a complex of clathrin, auxilin401-910 and Hsc70 at pH 6 in the presence of ATP, frozen within 20 seconds of adding Hsc70 in order to visualize events that follow the binding of Hsc70 to clathrin and auxilin before clathrin disassembly. In this map,we observe density beneath the vertex of the cage that we attribute to bound Hsc70. This density emerges asymmetrically from the clathrin vertex, suggesting preferential binding by Hsc70 for one of the three possible sites at the vertex. Statistical comparison with a map of whole auxilin and clathrin previously published by us reveals the location of statistically significant differences which implicate involvement of clathrin light chains in structural rearrangements which occur after Hsc70 is recruited. Clathrin disassembly assays using light scattering suggest that loss of clathrin light chains reduces the efficiency with which auxilin facilitates this reaction. These data support a regulatory role for clathrin light chains in clathrin disassembly in addition to their established role in regulating clathrin assembly. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The synthesis and properties of some hydrazines

A new synthetic method, applicable to the preparation of a wide range of hydrazine derivatives, is described. This involves the diborane reduction of a hydrazone, or, more conveniently, the reductive-condensation of a hydrazine and the appropriate aldehyde (or ketone). The method gives high yields and provides a particularly simple route to the relatively inaccessible 1,2-disubstituted hydrazines bearing a different group on each nitrogen. The new method has also been applied to the preparation of 1,2-disubstituted hydrazines with the same group on both nitrogens (via the azine), the very rare 1 ,2-disubstituted hydrazines bearing a tert-butyl group, trisubstituted hydrazines and monosubstituted hydrazines. Application of the reaction to the preparation of diaziridines has also been investigated. A mechanism for the reduction, supported by the isolation of a boron-containing intermediate, is suggested. Some limitations of the procedure are discussed. A general i.r. method of distinguishing the isomeric disubstituted hydrazines, as stable salts, has been developed. This has the advantages of speed and simplicity over previous methods. The mass spectra of a series of monosubstituted hydrazines, a series of 1,2-disubstituted hydrazines and some 1-benzoyl 2-alkylhydrazines have been examined in detail. The spectra are generally dominated byα -cleavage processes and the compounds show a variety of interesting rearrangement reactions. The mass spectra of some 1, 1-disubstituted hydrazines and some trisubstituted hydrazines have also been examined. Rearrangement processes occurring in the mass spectrum of tropylium fluoroborate have been examined. Similar rearrangements have been found in the spectrum of trityl fluoroborate and may be of general occurrence in the mass spectra of aromatic fluoroborates. Chemical shift values for some groups on hydrazine nitrogen are recorded and the results of tumour inhibitory tests on some hydrazines are also given.

Lessons for African economies from Irish and East Asian industry policy

When comparisons in terms of industrial policy lessons to be learned have taken place, it has tended to be solely vis-a-vis the ‘development state’ East Asian experience. This paper broadens the analysis and considers lessons which African countries can learn from other so-called ‘tiger’ economies including Ireland and the East and South Asian countries. We recognise that the latter are indeed clearly significant as many African countries at the time of independence had economic structures and levels of income quite similar to East Asian countries, yet have grown at vastly different rates since then. Exploring why this has been the case can thus offer important insights into possibilities for industrial policy. Yet this comes with some health warnings over East Asian experience. We suggest that another important contribution can come by looking at the Irish example, given its emphasis on corporatism rather than simply relying on state direction in the operation of industrial policy. The Irish model is also more democratic in some senses and has protected workers’ rights during the development process in contrast to the often highly dirigisite East Asian model. Overall we suggest that some immediate actions are needed, notably with regard to the financial system in small African economies. Without such changes, a poorly functioning financial system will continue to keep investment at low levels. In relation to the small size of the African economies, the paper recommends regional integration and sufficient overseas development assistance (ODA) for infrastructural development. It is also critical to note that the various small African economies each face their own industrial and economic development challenges, and that a ‘one size fits all’ approach is not appropriate; rather the key is to tailor policies and systems to the unique opportunities and development challenges in each African country.

A framework for assessing business-incubation input, process and output performance:proceedings of the RENT XXVII Conference, 20-22 November 2013, Vilnius, Lithuania

With business incubators deemed as a potent infrastructural element for entrepreneurship development, business incubation management practice and performance have received widespread attention. However, despite this surge of interest, scholars have questioned the extent to which business incubation delivers added value. Thus, there is a growing awareness among researchers, practitioners and policy makers of the need for more rigorous evaluation of the business incubation output performance. Aligned to this is an increasing demand for benchmarking business incubation input/process performance and highlighting best practice. This paper offers a business incubation assessment framework, which considers input/process and output performance domains with relevant indicators. This tool adds value on different levels. It has been developed in collaboration with practitioners and industry experts and therefore it would be relevant and useful to business incubation managers. Once a large enough database of completed questionnaires has been populated on an online platform managed by a coordinating mechanism, such as a business incubation membership association, business incubator managers can reflect on their practices by using this assessment framework to learn their relative position vis-à-vis their peers against each domain. This will enable them to align with best practice in this field. Beyond implications for business incubation management practice, this performance assessment framework would also be useful to researchers and policy makers concerned with business incubation management practice and impact. Future large-scale research could test for construct validity and reliability. Also, discriminant analysis could help link input and process indicators with output measures.

Gamification for servitization

The study described in this paper has set out to explore gamification from a servitization perspective to understand the opportunities and research challenges. A systematic literature review has been conducted to capture key characteristics of differing forms of gamification processes in a servitization context. The findings of our study focus on two area: (1) structural, organization’s physical bricksand-mortar attribute and (2) infrastructural, policies and practices in how structural aspects of servitization are to be managed. Six key findings are presented and collectively these contribute to our understanding of the broader gamification technologies that can help to transform servitization. The contribution of our research is twofold. First it captures a set of theoretical framework for analysing gamification in servitization context. Second, it provide an in-depth roadmap in how gamification can be applied to target major challenges in servitization.

Online-questionnaire design:establishing guidelines and evaluating existing eupport

As a new medium for questionnaire delivery, the internet has the potential to revolutionise the survey process. Online (web-based) questionnaires provide several advantages over traditional survey methods in terms of cost, speed, appearance, flexibility, functionality, and usability [1, 2]. For instance, delivery is faster, responses are received more quickly, and data collection can be automated or accelerated [1- 3]. Online-questionnaires can also provide many capabilities not found in traditional paper-based questionnaires: they can include pop-up instructions and error messages; they can incorporate links; and it is possible to encode difficult skip patterns making such patterns virtually invisible to respondents. Like many new technologies, however, online-questionnaires face criticism despite their advantages. Typically, such criticisms focus on the vulnerability of online-questionnaires to the four standard survey error types: namely, coverage, non-response, sampling, and measurement errors. Although, like all survey errors, coverage error (“the result of not allowing all members of the survey population to have an equal or nonzero chance of being sampled for participation in a survey” [2, pg. 9]) also affects traditional survey methods, it is currently exacerbated in online-questionnaires as a result of the digital divide. That said, many developed countries have reported substantial increases in computer and internet access and/or are targeting this as part of their immediate infrastructural development [4, 5]. Indicating that familiarity with information technologies is increasing, these trends suggest that coverage error will rapidly diminish to an acceptable level (for the developed world at least) in the near future, and in so doing, positively reinforce the advantages of online-questionnaire delivery. The second error type – the non-response error – occurs when individuals fail to respond to the invitation to participate in a survey or abandon a questionnaire before it is completed. Given today’s societal trend towards self-administration [2] the former is inevitable, irrespective of delivery mechanism. Conversely, non-response as a consequence of questionnaire abandonment can be relatively easily addressed. Unlike traditional questionnaires, the delivery mechanism for online-questionnaires makes estimation of questionnaire length and time required for completion difficult1, thus increasing the likelihood of abandonment. By incorporating a range of features into the design of an online questionnaire, it is possible to facilitate such estimation – and indeed, to provide respondents with context sensitive assistance during the response process – and thereby reduce abandonment while eliciting feelings of accomplishment [6]. For online-questionnaires, sampling error (“the result of attempting to survey only some, and not all, of the units in the survey population” [2, pg. 9]) can arise when all but a small portion of the anticipated respondent set is alienated (and so fails to respond) as a result of, for example, disregard for varying connection speeds, bandwidth limitations, browser configurations, monitors, hardware, and user requirements during the questionnaire design process. Similarly, measurement errors (“the result of poor question wording or questions being presented in such a way that inaccurate or uninterpretable answers are obtained” [2, pg. 11]) will lead to respondents becoming confused and frustrated. Sampling, measurement, and non-response errors are likely to occur when an online-questionnaire is poorly designed. Individuals will answer questions incorrectly, abandon questionnaires, and may ultimately refuse to participate in future surveys; thus, the benefit of online questionnaire delivery will not be fully realized. To prevent errors of this kind2, and their consequences, it is extremely important that practical, comprehensive guidelines exist for the design of online questionnaires. Many design guidelines exist for paper-based questionnaire design (e.g. [7-14]); the same is not true for the design of online questionnaires [2, 15, 16]. The research presented in this paper is a first attempt to address this discrepancy. Section 2 describes the derivation of a comprehensive set of guidelines for the design of online-questionnaires and briefly (given space restrictions) outlines the essence of the guidelines themselves. Although online-questionnaires reduce traditional delivery costs (e.g. paper, mail out, and data entry), set up costs can be high given the need to either adopt and acquire training in questionnaire development software or secure the services of a web developer. Neither approach, however, guarantees a good questionnaire (often because the person designing the questionnaire lacks relevant knowledge in questionnaire design). Drawing on existing software evaluation techniques [17, 18], we assessed the extent to which current questionnaire development applications support our guidelines; Section 3 describes the framework used for the evaluation, and Section 4 discusses our findings. Finally, Section 5 concludes with a discussion of further work.

Enhanced connectivity and QoE through LTE-WiFi interworking in Smart Cities

Mobile communication and networking infrastructures play an important role in the development of smart cities, to support real-time information exchange and management required in modern urbanization. Mobile WiFi devices that help offloading data traffic from the macro-cell base station and serve the end users within a closer range can significantly improve the connectivity of wireless communications between essential components including infrastructural and human devices in a city. However, this offloading function through interworking between LTE and WiFi systems will change the pattern of resource distributions operated by the base station. In this paper, a resource allocation scheme is proposed to ensure stable service coverage and end-user quality of experience (QoE) when offloading takes place in a macro-cell environment. In this scheme, a rate redistribution algorithm is derived to form a parametric scheduler to meet the required levels of efficiency and fairness, guided by a no-reference quality assessment metric. We show that the performance of resource allocation can be regulated by this scheduler without affecting the service coverage offered by the WLAN access point. The performances of different interworking scenarios and macro-cell scheduling policies are also compared.

Exploring the biological basis for Salmonella persistence in food manufacturing environments

The persistence of Salmonella spp. in low moisture foods is a challenge for the food industry as despite control strategies already in place, notable outbreaks still occur. The aim of this study was to characterise isolates of Salmonella, known to be persistent in the food manufacturing environment, by comparing their microbiological characteristics with a panel of matched clinical and veterinary isolates. The gross morphology of the challenge panel was phenotypically characterised in terms of cellular size, shape and motility. In all the parameters measured, the factory isolates were indistinguishable from the human, clinical and veterinary strains. Further detailed metabolic profiling was undertaken using the biolog Microbial ID system. Multivariate analysis of the metabolic microarray revealed differences in metabolism of the factory isolate of S.Montevideo, based on its upregulated ability to utilise glucose and the sugar alcohol groups. The remainder of the serotype-matched isolates were metabolically indistinguishable. Temperature and humidity are known to influence bacterial survival and through environmental monitoring experimental parameters were defined. The results revealed Salmonella survival on stainless steel was affected by environmental temperatures that may be experienced in a food processing environment; with higher survival rates (D25=35.4) at temperatures at 25°C and lower humidity levels of 15% RH, however a rapid decline in cell count (D10=3.4) with lower temperatures of 10°C and higher humidity of 70% RH. Several resident factories strains survived in higher numbers on stainless steel (D25=29.69) compared to serotype matched clinical and veterinary isolates (D25=22.98). Factory isolates of Salmonella did not show an enhanced growth rate in comparison to serotype matched solates grown in Luria broth, Nutrient broth and M9 minimal media indicating that as an independent factor, growth was unlikely to be a major factor driving Salmonella persistence. Using a live / dead stain coupled with fluorescence microscopy revealed that when no longer culturable, isolates of S.Schwarzengrund entered into a viable nonculturable state. The biofilm forming capacity of the panel was characterised and revealed that all were able to form biofilms. None of the factory isolates showed an enhanced capability to form biofilms in comparison to serotype-matched isolates. In disinfection studies, planktonic cells were more susceptible to disinfectants than cells in biofilm and all the disinfectants tested were successful in reducing bacterial load. Contact time was one of the most important factors for reducing bacterial populations in a biofilm. The genomes of eight strains were sequenced. At the nucleotide and amino acid level the food factory isolates were similar to those of isolates from other environments; no major genomic rearrangements were observed, supporting the conclusions of the phenotypic and metabolic analysis. In conclusion, having investigated a variety of morphological, biochemical and genomic factors, it is unlikely that the persistence of Salmonella in the food manufacturing environment is attributable to a single phenotypic, metabolic or genomic factor. Whilst a combination of microbiological factors may be involved it is also possible that strain persistence in the factory environment is a consequence of failure to apply established hygiene management principles.