Role of fibroblast growth factor receptor in regulation of membrane traffic

Several studies show that membrane transport mechanisms are regulated by signalling molecules. Recently, genome-wide screen analyses in C.elegans have enabled scientists to identify novel regulators in membrane trafficking and also signalling molecules which are found to couple with this machinery. Fibroblast growth factor (FGF) via binding to fibroblast growth factor receptor (FGFR) mediate signals which are essential in the development of an organism, patterning, cell migration and tissue homeostasis. Impaired FGFR-mediated signalling has been associated with various developmental, neoplastic, metabolic and neurological diseases and cancer. In this study, the potential role of FGFR-mediated signalling pathway as a regulator of membrane trafficking was investigated. The GFP-tagged yolk protein YP170-GFP trafficking was analysed in worms where 1) FGFR signalling cascade components were depleted by RNAi and 2) in mutant animals. From these results, it was found that the disruption of the genes egl-15 (FGFR), egl-17(FGF), let-756(FGF), sem-5, let-60, lin-45, mek-2, mpk-1 and plc-3 lead to abnormal localization of YP170-GFP, suggesting that signalling downstream of FGFR via activation of MAPK and PLC-γ pathway is regulating membrane transport. The route of trafficking was further investigated, to pinpoint which membrane step is regulated by worm FGFR, by analysing a number of GFP-tagged intracellular membrane markers in the intestine of Wild Type (WT) and FGFR mutant worms. FGFR mutant worms showed a significant difference in the localisation of several endosomal membrane markers, suggesting its regulatory role in early and recycling steps of endocytosis. Finally, the trafficking of transferrin in a mammalian NIH/3T3 cell line was investigated to identify the conservation of these membrane trafficking regulatory mechanisms between organisms. Results showed no significant changes in transferrin trafficking upon FGFR stimulation or inhibition.

Practice report: the role of environmental factors in industrial site selection activities: a case of limestone quarry expansion in Barbados, West Indies

Site selection is a key activity for quarry expansion to support cement production, and is governed by factors such as resource availability, logistics, costs, and socio-environmental factors. Adequate consideration of all factors facilitates both industrial productivity and sustainable economic growth. This study illustrates the site selection process that was undertaken for the expansion of limestone quarry operations to support cement production in Barbados. First, alternate sites with adequate resources to support a 25-year development horizon were identified. Second, socio-environmental conditions were described and potential impacts identified. Third, a comparative matrix was constructed to evaluate relative site characteristics with respect to physical, ecological, socio-cultural and economic factors. The study shows that environmental factors were essential to the final site recommendation.

Privatisation and sustainable competitive advantage in the emerging economies of Central Europe

Extant research on the impact of privatization in the Central Europe (CE) region has focused on improvements in efficiency and the nature of cost-based advantages. This study argues that the development of a vibrant privatized sector requires attention to the broader resource configurations of domestic enterprises. Empirical research was conducted on a large sample of firms in Poland, Hungary and Slovenia. Foreign investment was found to significantly impact on resource accumulation with implications for the development of strategic capabilities and competitive advantage. Foreign direct investment is an effective vehicle for the transfer of financial resources, reputation and new brands but not organizational capabilities. In terms of practice, this study demonstrates the important role of outside investment in the development of a firm's resource base (Frydman et al. 1999). Companies can gain a competitive advantage in their domestic markets through gaining access to the resources of foreign investors.

Identification, mutagenesis, and transcriptional analysis of the methanesulfonate transport operon of methylosulfonomonas methylovora

Recently identified genes located downstream (3') of the msmEF (transport encoding) gene cluster, msmGH, and located 5' of the structural genes for methanesulfonate monooxygenase (MSAMO) are described from Methylosulfonomonas methylovora. Sequence analysis of the derived polypeptide sequences encoded by these genes revealed a high degree of identity to ABC-type transporters. MsmE showed similarity to a putative periplasmic substrate binding protein, MsmF resembled an integral membraneassociated protein, and MsmG was a putative ATP-binding enzyme. MsmH was thought to be the cognate permease component of the sulfonate transport system. The close association of these putative transport genes to the MSAMO structural genes msmABCD suggested a role for these genes in transport of methanesulfonic acid (MSA) into M. methylovora. msmEFGH and msmABCD constituted two operons for the coordinated expression of MSAMO and the MSA transporter systems. Reverse-transcription-PCR analysis of msmABCD and msmEFGH revealed differential expression of these genes during growth on MSA and methanol. The msmEFGH operon was constitutively expressed, whereas MSA induced expression of msmABCD. A mutant defective in msmE had considerably slower growth rates than the wild type, thus supporting the proposed role of MsmE in the transport of MSA into M. methylovora.

Industrial relations in the road passenger transport industry-a political-economic analysis.

This thesis examines the British Bus and Tram Industry from 1889 to 1988. The first determinant of the pattern of industrial relations is the development of the labour-process. The labour process changes with the introduction of new technology (electrified trams and mechanised buses), the concentration and centralisation of ownership, the decline of competition, changing market position, municipal and state regulation, ownership and control. The tram industry, as a consequence of electrification, is almost wholly municipally owned and the history of the labour process from horse-trams to the decline of the industry is examined. The bus industry has a less unified structure and is examined by sector; London, Municipal, and Territorial/Provincial. The small independent sector is largely ignored. The labour process is examined from the horse-bus to the present day. The development of resistance in the labour process is discussed both as a theoretical problematic (the `Braverman Debate') and through the process of unionisation, the centralisation and bureaucratisation of the unions, the development of national bargaining structures (National Joint Industrial Council and the National Council for the Omnibus Industry), and the development of resistance to those processes. This resistance takes either a syndicalist form, or under Communist Party leadership the form of rank and file movements, or simply unofficial organisations of branch officials. The process of centralisation of the unions, bureaucratisation and the institutionalisation of bargaining and the relationship between this process and the role of the Unions in the Labour Party is examined. Neo-corporatism, that is the increasing integration of the leadership of the main Union, the T.G.W.U.with the Labour Party and with the State is discussed. In theoretical terms, this thesis considers the debate around the notion of `labour process', the relationship between labour process and labour politics and between labour process and labour history. These relationships are placed within a discussion of class consciousness.

Role of β-adrenergic receptors in the anti-obesity and anti-diabetic effects of zinc-α2-glycoprotien (ZAG)

Objectives: The goal of the current study is to determine whether the ß-adrenoreceptor (ß-AR) plays a role in the anti-obesity and anti-diabetic effects of zinc-a2-glycoprotein (ZAG). Material and methods: This has been investigated in CHO-K1 cells transfected with the human ß1-, ß2-, ß3-AR and in ob/ob mice. Cyclic AMP assays were carried out along with binding studies. Ob/ob mice were treated with ZAG and glucose transportation and insulin were examined in the presence or absence of propranolol. Results: ZAG bound to the ß3-AR with higher affinity (Kd 46±1nM) than the ß2-AR (Kd 71±3nM) while there was no binding to the ß1-AR, and this correlated with the increases in cyclic AMP in CHO-K1 cells transfected with the various ß-AR and treated with ZAG. Treatment of ob/ob mice with ZAG increased protein expression of ß3-AR in gastrocnemius muscle, and in white and brown adipose tissues, but had no effect on expression of ß1- and ß2-AR. A reduction of body weight was seen and urinary glucose excretion, increase in body temperature, reduction in maximal plasma glucose and insulin levels in the oral glucose tolerance test, and stimulation of glucose transport into skeletal muscle and adipose tissue, were completely attenuated by the non-specific ß-AR antagonist propranolol. Conclusion: The results suggest that the effects of ZAG on body weight and insulin sensitivity in ob/ob mice are manifested through a ß-3AR, or possibly a ß2-AR.

Greening operations management:an online sustainable procurement course for practitioners

In the Operations Management field, sustainable procurement has emerged as a way to green the purchasing and supply process. This paper explores issues in sustainable procurement training. The authors formed an interdisciplinary team to design, deliver and evaluate a training programme to promote and develop sustainable procurement in the United Kingdom health sector. Particular features of the project were its engagement with evolving and contested understandings of sustainable procurement and of the underlying concept of sustainable development and its recognition that relevant knowledge in the field is both incomplete and widely diffused through the procurement community. Eight practitioner groups worked together on themes to develop their understanding of sustainable procurement using the Blackboard virtual learning environment. Group interviews were conducted upon completion of the course and again three months later to explore qualitatively participants' experience of learning and implementing sustainable procurement. Although the course was delivered to practitioners, it might be modified for undergraduate and graduate students as it comprised the use of online activities in virtual learning environments, case studies and a broad range of literature. The course was also particularly significant in the context of contemporary policy moves in the United Kingdom and elsewhere to promote the role of higher education institutions in delivering workplace-based, high-skills education consistent with strategic policy considerations (see, for example, DIUS, 2008).

Institutional work at field-configuring events:shaping industry change within sustainable transitions

Adopting an institutional approach from organization studies, this paper explores the role of key actors on “purposeful governance for sustainability” (Smith, Voss et al. 2010: 444) through the case of smart metering in the UK. Institutions are enduring patterns in social life, reflected in identities, routines, rules, shared meanings and social relations, which enable, and constrain, the beliefs and behaviours of individual and collective actors within a field (Thornton and Ocasio 2008). Large-scale external initiatives designed to drive regime-level change prompt ‘institutional entrepreneurs’ to perform ‘institutional work’ – “purposive action aimed at creating, maintaining and disrupting institutions” (Lawrence and Suddaby, 2006). Organization scholars are giving increasing attention to ‘field-configuring events’ (FCEs) which provide social spaces for diverse organizational actors to come together to collectively shape socio-technical pathways (Lampel and Meyer 2008). Our starting point for this exploratory study is that FCEs can offer important insights to the dynamics, politics and governance of sustainability transitions. Methodologically, FCEs allow us to observe and “link field evolution at the macro-level with individual action at the micro-level” (Lampel and Meyer, 2008: 1025). We examine the work of actors during a series of smart metering industry forums over a three-year period (industry presentations [n= 77] and panel discussions [n= 16]). The findings reveal new insights about how institutional change unfolds, alongside technological transitions, in ways that are partial and aligned with the interests of powerful incumbents whose voices are frequently heard at FCEs. The paper offers three contributions. First, the study responds to calls for more research examining FCEs and the role they play in transforming institutional fields. Second, the emergent findings extend research on institutional work by advancing our understanding of a specific site of institutional work, namely a face-to-face inter-organizational arena. Finally, in line with the research agenda for innovation studies and sustainability transitions elaborated by Smith et al (2010), the paper illustrates how actors in a social system respond to, translate, and enact interventions designed to promote industrial transformation, ultimately shaping the sustainability transition pathway.

IT as enabler of sustainable farming:an empirical analysis of farmers' adoption decision of precision agriculture technology

Precision agriculture (PA) describes a suite of IT based tools which allow farmers to electronically monitor soil and crop conditions and analyze treatment options. This study tests a model explaining the difficulties of PA technology adoption. The model draws on theories of technology acceptance and diffusion of innovation and is validated using survey data from farms in Canada. Findings highlight the importance of compatibility among PA technology components and the crucial role of farmers' expertise. The model provides the theoretical and empirical basis for developing policies and initiatives to support PA technology adoption.

Reverse resource exchanges in service supply chains:the case of returnable transport packaging

Purpose: The purpose of this paper is to understand how reverse resource exchanges and resource dependencies are managed in the service supply chain (SSC) of returnable transport packaging (RTP). Design/methodology/approach: A single case study was conducted in the context of automotive logistics focusing on the RTP SSC. Data were collected through 16 interviews, primarily with managers of a logistics service provider (LSP) and document analysis of contractual agreements with key customers of the packaging service. Findings: Resource dependencies among actors in the SSC result from the importance of the RTP for the customer’s production processes, the competition among users for RTP and the negative implications of the temporary unavailability of RTP for customers and the LSP (in terms of service performance). Amongst other things, the LSP is dependent on its customers and third-party users (e.g. the customer’s suppliers) for the timely return of package resources. The role of inter-firm integration and collaboration, formal contracts as well as customers’ power and influence over third-party RTP users are stressed as key mechanisms for managing LSP’s resource dependencies. Research limitations/implications: A resource dependence theory (RDT) lens is used to analyse how reverse resource exchanges and associated resource dependencies in SSCs are managed, thus complementing the existing SSC literature emphasising the bi-directionality of resource flows. The study also extends the recent SSC literature stressing the role of contracting by empirically demonstrating how formal contracts can be mobilised to explicate resource dependencies and to specify, and regulate, reverse exchanges in the SSC. Practical implications: The research suggests that logistics providers can effectively manage their resource dependencies and regulate reverse exchanges in the SSC by deploying contractual governance mechanisms and leveraging their customers’ influence over third-party RTP users. Originality/value: The study is novel in its application of RDT, which enhances our understanding of the management of reverse exchanges and resource dependencies in SSCs.

Logistics by rail:is this the key to more sustainable traffic policies in Northern Germany?

Despite the fact that Germany has a well- expanded traffic infrastructure, the country con-fronts a strong growth in freight volumes and it is very likely that in the forthcoming yearsit will not be able to reasonably cope with the increasing demand. Against this back-ground, the aim of this paper is to provide an in-depth analysis of the transport sector in North Germany in an effort to identify, if any, the possibilities of collapse as a result of the continuous increase in the demand of freight traffic. The research based on the DelphiTechnique, collects, analyses and summarizes the opinions of a group of experts in theaforementioned issues. Results indicate that railways could represent the solution to theforecasted growing freight volumes in the next years, not only in Germany, but also in thewhole European transport sector. In spite of continuous efforts undertaken by the politicsand the economy, the existing logistics and freight traffic concepts are not sufficient. Fi-nancing is too scarce; traffic concepts take issues like sustainability, environment protec-tion and working conditions into little consideration.

Role of GSH in estrone sulfate binding and translocation by the multidrug resistance protein 1 (MRP1/ABCC1)

Multidrug resistance protein 1 (MRP1/ABCC1) is an ATP-dependent efflux pump that can confer resistance to multiple anticancer drugs and transport conjugated organic anions. Unusually, transport of several MRP1 substrates requires glutathione (GSH). For example, estrone sulfate transport by MRP1 is stimulated by GSH, vincristine is co-transported with GSH, or GSH can be transported alone. In the present study, radioligand binding assays were developed to investigate the mechanistic details of GSH-stimulated transport of estrone sulfate by MRP1. We have established that estrone sulfate binding to MRP1 requires GSH, or its non-reducing analogue S-methyl GSH (S-mGSH), and further that the affinity (Kd) of MRP1 for estrone sulfate is 2.5-fold higher in the presence of S-mGSH than GSH itself. Association kinetics show that GSH binds to MRP1 first, and we propose that GSH binding induces a conformational change, which makes the estrone sulfate binding site accessible. Binding of non-hydrolyzable ATP analogues to MRP1 decreases the affinity for estrone sulfate. However, GSH (or S-mGSH) is still required for estrone sulfate binding, and the affinity for GSH is unchanged. Estrone sulfate affinity remains low following hydrolysis of ATP. The affinity for GSH also appears to decrease in the post-hydrolytic state. Our results indicate ATP binding is sufficient for reconfiguration of the estrone sulfate binding site to lower affinity and argue for the presence of a modulatory GSH binding site not associated with transport of this tripeptide. A model for the mechanism of GSH-stimulated estrone sulfate transport is proposed.

The role of third party logistics providers (3PLs) in the adoption of green supply chain initiatives

The increasing importance of environmental sustainability has sharpened the focus on the need for innovative approaches to the purchasing of transport and logistics services. This article points out some of the challenges that purchasers of transport and logistics services, as well as their suppliers in the third party logistics (3PL) industry, are facing. These include the need for closer collaboration between 3PLs and their customers, as well as developing systems for the robust assessment of the environmental sustainability of services. The article is based on several years’ research experience in Ireland, Italy and Sweden.

Purchasing green transport and logistics services:implications from the environmental sustainability attitude of 3PLs

Environmental sustainability is an area of increasing importance for third party logistics (3PL) companies. As the design and implementation of services requires interaction between buyer and 3PL, the 3PLs are in a critical position to support the efforts towards greening operations of different supply chain participants. However the literature in this field reflects a gap between the perspectives of buyers and 3PLs. This chapter attempts to fill this void through an explorative case study analysis on the environmental attitude of 3PLs in order to derive implications for buyers’ behavior. The results indicate that the buyer’s role is critical in different ways in the development of green initiatives among 3PLs. An increased orientation towards longer-term contracts and joint development would likely enhance the level of green initiatives. Indirectly, the buyer has the opportunity to influence its 3PLs through interaction with employees on different levels in the company, including top management.

An agent approach to improving radio frequency identification enabled Returnable Transport Equipment

Returnable transport equipment (RTE) such as pallets form an integral part of the supply chain and poor management leads to costly losses. Companies often address this matter by outsourcing the management of RTE to logistics service providers (LSPs). LSPs are faced with the task to provide logistical expertise to reduce RTE related waste, whilst differentiating their own services to remain competitive. In the current challenging economic climate, the role of the LSP to deliver innovative ways to achieve competitive advantage has never been so important. It is reported that radio frequency identification (RFID) application to RTE enables LSPs such as DHL to gain competitive advantage and offer clients improvements such as loss reduction, process efficiency improvement and effective security. However, the increased visibility and functionality of RFID enabled RTE requires further investigation in regards to decision‐making. The distributed nature of the RTE network favours a decentralised decision‐making format. Agents are an effective way to represent objects from the bottom‐up, capturing the behaviour and enabling localised decision‐making. Therefore, an agent based system is proposed to represent the RTE network and utilise the visibility and data gathered from RFID tags. Two types of agents are developed in order to represent the trucks and RTE, which have bespoke rules and algorithms in order to facilitate negotiations. The aim is to create schedules, which integrate RTE pick‐ups as the trucks go back to the depot. The findings assert that: - agent based modelling provides an autonomous tool, which is effective in modelling RFID enabled RTE in a decentralised utilising the real‐time data facility. ‐ the RFID enabled RTE model developed enables autonomous agent interaction, which leads to a feasible schedule integrating both forward and reverse flows for each RTE batch. ‐ the RTE agent scheduling algorithm developed promotes the utilisation of RTE by including an automatic return flow for each batch of RTE, whilst considering the fleet costs andutilisation rates. ‐ the research conducted contributes an agent based platform, which LSPs can use in order to assess the most appropriate strategies to implement for RTE network improvement for each of their clients.