In silico identified CCR4 antagonists target regulatory T cells and exert adjuvant activity in vaccination

Adjuvants are substances that enhance immune responses and thus improve the efficacy of vaccination. Few adjuvants are available for use in humans, and the one that is most commonly used (alum) often induces suboptimal immunity for protection against many pathogens. There is thus an obvious need to develop new and improved adjuvants. We have therefore taken an approach to adjuvant discovery that uses in silico modeling and structure-based drug-design. As proof-of-principle we chose to target the interaction of the chemokines CCL22 and CCL17 with their receptor CCR4. CCR4 was posited as an adjuvant target based on its expression on CD4(+)CD25(+) regulatory T cells (Tregs), which negatively regulate immune responses induced by dendritic cells (DC), whereas CCL17 and CCL22 are chemotactic agents produced by DC, which are crucial in promoting contact between DC and CCR4(+) T cells. Molecules identified by virtual screening and molecular docking as CCR4 antagonists were able to block CCL22- and CCL17-mediated recruitment of human Tregs and Th2 cells. Furthermore, CCR4 antagonists enhanced DC-mediated human CD4(+) T cell proliferation in an in vitro immune response model and amplified cellular and humoral immune responses in vivo in experimental models when injected in combination with either Modified Vaccinia Ankara expressing Ag85A from Mycobacterium tuberculosis (MVA85A) or recombinant hepatitis B virus surface antigen (rHBsAg) vaccines. The significant adjuvant activity observed provides good evidence supporting our hypothesis that CCR4 is a viable target for rational adjuvant design.

Assessment of physical and hydrological properties of biological soil crusts using x-ray microtomography and modelling

Biological soil crusts (BSCs) are formed by aggregates of soil particles and communities of microbial organisms and are common in all drylands. The role of BSCs on infiltration remains uncertain due to the lack of data on their role in affecting soil physical properties such as porosity and structure. Quantitative assessment of these properties is primarily hindered by the fragile nature of the crusts. Here we show how the use of a combination of non-destructive imaging X-ray microtomography (XMT) and Lattice Boltzmann method (LBM) enables quantification of key soil physical parameters and the modeling of water flow through BSCs samples from Kalahari Sands, Botswana. We quantify porosity and flow changes as a result of mechanical disturbance of such a fragile cyanobacteria-dominated crust. Results show significant variations in porosity between different types of crusts and how they affect the flow and that disturbance of a cyanobacteria-dominated crust results in the breakdown of larger pore spaces and reduces flow rates through the surface layer. We conclude that the XMT–LBM approach is well suited for study of fragile surface crust samples where physical and hydraulic properties cannot be easily quantified using conventional methods.

Forms of capital, mixed embeddedness and Somali enterprise

What form is small business activity taking among new migrants in the UK? This question is addressed by examining the case of Somalis in the English city of Leicester.We apply a novel synthesis of the Nee and Sanders' (2001) `forms of capital' model with the `mixed embeddedness' approach (Rath, 2000) to enterprises established by newly arrived immigrant communities, combining agency and structure perspectives. Data are drawn from business-owners (and workers) themselves, rather than community representatives. Face-to-face in-depth interviews were held with 25 business owners and 25 employees/`helpers', supplemented by 3 focus group encounters with different segments of the Somali business population.The findings indicate that a reliance solely on social capital explanations is not sufficient. An adequate understanding of business dynamics requires an appreciation of how Somalis mobilize different forms of capital within a given political, social and economic context.

Protestantism, nation and diaspora in Imperial Germany

This article examines the close connection between Protestantism and nationalism in Imperial Germany within a transnational context. In the years before 1914, the Prussian State Church in particular strengthened the legal and organisational framework for an increasing number of diaspora congregations to become attached. These acted as an important vehicle to embed the nationalist rhetoric produced within the Reich into emigrants' notions of belonging. Whilst previous scholarship has noted this connection in general, the article sheds more detailed light on the mechanics and structure, but also on the limits, of this process. Feedback processes from periphery to centre, in turn, had an impact on German national identity construction as that of a nation that was not confined to state borders. Applying a constructionist theoretical framework, the contested question of whether the heterogeneity of Germans abroad allows for the application of the diaspora concept is answered affirmatively.

Extreme events, organizations and the politics of decision making

Purpose – Threats of extreme events, such as terrorist attacks or infrastructure breakdown, are potentially highly disruptive events for all types of organizations. This paper seeks to take a political perspective to power in strategic decision making and how this influences planning for extreme events. Design/methodology/approach – A sample of 160 informants drawn from 135 organizations, which are part of the critical national infrastructure in the UK, forms the empirical basis of the paper. Most of these organizations had publicly placed business continuity and preparedness as a strategic priority. The paper adopts a qualitative approach, coding data from focus groups. Findings – In nearly all cases there is a pre-existing dominant coalition which keeps business continuity decisions off the strategic agenda. The only exceptions to this are a handful of organizations which provide continuous production, such as some utilities, where disruption to business as usual can be readily quantified. The data reveal structural and decisional elements of the exercise of power. Structurally, the dominant coalition centralizes control by ensuring that only a few functional interests participate in decision making. Research limitations/implications – Decisional elements of power emphasize the dominance of calculative rationality where decisions are primarily made on information and arguments which can be quantified. Finally, the paper notes the recursive aspect of power relations whereby agency and structure are mutually constitutive over time. Organizational structures of control are maintained, despite the involvement of managers charged with organizational preparedness and resilience, who remain outside the dominant coalition. Originality/value – The paper constitutes a first attempt to show how planning for emergencies fits within the strategy-making process and how politically controlled this process is.

An interdisciplinary approach to designing and evaluating a hybrid solar-biomass power plant

Purpose: Energy security is a major concern for India and many rural areas remain un-electrified. Thus, innovations in sustainable technologies to provide energy services are required. Biomass and solar energy in particular are resources that are widely available and underutilised in India. This paper aims to provide an overview of a methodology that was developed for designing and assessing the feasibility of a hybrid solar-biomass power plant in Gujarat. Design/methodology/approach: The methodology described is a combination of engineering and business management studies used to evaluate and design solar thermal collectors for specific applications and locations. For the scenario of a hybrid plant, the methodology involved: the analytical hierarchy process, for solar thermal technology selection; a cost-exergy approach, for design optimisation; quality function deployment, for designing and evaluating a novel collector - termed the elevation linear Fresnel reflector (ELFR); and case study simulations, for analysing alternative hybrid plant configurations. Findings: The paper recommended that for a hybrid plant in Gujarat, a linear Fresnel reflector of 14,000 m2 aperture is integrated with a 3 tonne per hour biomass boiler, generating 815 MWh per annum of electricity for nearby villages and 12,450 tonnes of ice per annum for local fisheries and food industries. However, at the expense of a 0.3 ¢/kWh increase in levelised energy costs, the ELFR can increase savings of biomass (100 t/a) and land (9 ha/a). Research limitations/implications: The research reviewed in this paper is primarily theoretical and further work will need to be undertaken to specify plant details such as piping layout, pump sizing and structure, and assess plant performance during real operational conditions. Originality/value: The paper considers the methodology adopted proved to be a powerful tool for integrating technology selection, optimisation, design and evaluation and promotes interdisciplinary methods for improving sustainable engineering design and energy management. © Emerald Group Publishing Limited.

A case study analysis on information and communication technology usage in small logistics service companies

The impact of ICT (information and communications technology) on the logistics service industry is reshaping its organisation and structure. Within this process, the nature of changes resulting from ICT dissemination in small 3PLs (third party logistics providers) is still unclear, although a large number of logistics service markets, especially in the EU context, are populated by a high number of small 3PLs. In addition, there is still a gap in the literature where the role of technological capability in small 3PLs is seriously underestimated. This gives rise to the need to develop investigation in this area. The paper presents the preliminary results of a case study analysis on ICT usage in a sample of 7 small Italian 3PLs. The results highlight some of the barriers to effective ICT implementation, as well as some of the critical success factors.

Eastern Christianity and politics in the Twenty-First Century

This book provides an up-to-date, comprehensive overview of Eastern Christian churches in Europe, the Middle East, America, Africa, Asia and Australia. Written by leading international scholars in the field, it examines both Orthodox and Oriental churches from the end of the Cold War up to the present day. The book offers a unique insight into the myriad church-state relations in Eastern Christianity and tackles contemporary concerns, opportunities and challenges, such as religious revival after the fall of communism; churches and democracy; relations between Orthodox, Catholic and Greek Catholic churches; religious education and monastic life; the size and structure of congregations; and the impact of migration, secularisation and globalisation on Eastern Christianity in the twenty-first century.

Global HR roles and factors influencing their development:evidence from emerging Indian IT services multinationals

The rapid growth of emerging markets’ multinational companies (MNCs) is a recent phenomenon and, as such, their nature and structure of key management processes, functions, and roles need further examination. While an abundance of low-cost labor is often the starting point of competitive advantage for many of the emerging markets’ MNCs, it is the optimum configuration of people, processes, and technology that defines how they leverage their intangible resources. Based on case studies of four Indian IT services MNCs, involving 51 in-depth interviews of business and human resource (HR) leaders at the corporate and subsidiary levels, we identify five key HR roles—namely, strategic business partner, guardian of culture, builder of global workforce and capabilities, champion of processes, and facilitator of employee development. The analysis also highlights that the HR function in Indian IT service MNCs faces several challenges in consolidating the early gains of internationalization, such as lack of decentralized decision making, developing a global mind-set, localization of the workforce, and developing a global leadership pipeline. Based on our exploratory findings, we propose a framework outlining the global HR roles pursued by emerging IT services MNCs, the factors influencing them, and the challenges facing their HR function for future research.

From art for arts sake to art as means of knowing:a rationale for advancing arts-based methods in research, practice and pedagogy

This paper advances a philosophically informed rationale for the broader, reflexive and practical application of arts-based methods to benefit research, practice and pedagogy. It addresses the complexity and diversity of learning and knowing, foregrounding a cohabitative position and recognition of a plurality of research approaches, tailored and responsive to context. Appreciation of art and aesthetic experience is situated in the everyday, underpinned by multi-layered exemplars of pragmatic visual-arts narrative inquiry undertaken in the third, creative and communications sectors. Discussion considers semi-guided use of arts-based methods as a conduit for topic engagement, reflection and intersubjective agreement; alongside observation and interpretation of organically employed approaches used by participants within daily norms. Techniques span handcrafted (drawing), digital (photography), hybrid (cartooning), performance dimensions (improvised installations) and music (metaphor and structure). The process of creation, the artefact/outcome produced and experiences of consummation are all significant, with specific reflexivity impacts. Exploring methodology and epistemology, both the "doing" and its interpretation are explicated to inform method selection, replication, utility, evaluation and development of cross-media skills literacy. Approaches are found engaging, accessible and empowering, with nuanced capabilities to alter relationships with phenomena, experiences and people. By building a discursive space that reduces barriers; emancipation, interaction, polyphony, letting-go and the progressive unfolding of thoughts are supported, benefiting ways of knowing, narrative (re)construction, sensory perception and capacities to act. This can also present underexplored researcher risks in respect to emotion work, self-disclosure, identity and agenda. The paper therefore elucidates complex, intricate relationships between form and content, the represented and the representation or performance, researcher and participant, and the self and other. This benefits understanding of phenomena including personal experience, sensitive issues, empowerment, identity, transition and liminality. Observations are relevant to qualitative and mixed methods researchers and a multidisciplinary audience, with explicit identification of challenges, opportunities and implications.

Understanding the IT-related attitudes and needs of persons with age-related macular degeneration:a case study

In the UK, 20 per cent of people aged 75 years and over are living with sight loss; this percentage is expected to increase as the population ages (RNIB, 2011). Age-Related Macular Degeneration (AMD) is the UK’s leading cause of severe visual impairment amongst the elderly. It accounts for 16,000 blind/partial sight registrations per year and is the leading cause of blindness among people aged 55 years and older in western countries (Bressler, 2004). Our ultimate goal is to develop an assistive mobile application to support accurate and convenient diet data collection on which basis to then provide customised dietary advice and recommendations in order to help support individuals with AMD to mitigate their ongoing risk and retard the progression of the disease. In this paper, we focus on our knowledge elicitation activities conducted to help us achieve a deep and relevant understanding of our target user group. We report on qualitative findings from focus groups and observational studies with persons with AMD and interviews with domain experts which enable us to fully appreciate the impact that technology may have on our intended users as well as to inform the design and structure of our proposed mobile assistive application.