An empirical study of the imperatives for a supply chain implementation project in Seagate Technology International

Singapore's electronics manufacturers are facing many questions. In the computer hard-drive industry, where the problem of obsolescence is common and where a product's lifecycle may be only six months, manufacturers are anxious to know what the next order-winning criteria will be. Since low labour costs are no longer a key factor, many organisations are developing their competencies in research and development, sales and marketing, logistics and supply chain management in order to maintain competitiveness. This paper illustrates how Seagate has envisaged a climate of cooperation and collaboration to better serve its customers in the areas of technology, cost and delivery. The paper is based on observations and findings following a longitudinal case study approach at the Seagate Storage Product Group (SPG) in Singapore. The seven-stage implementation framework adopted by Seagate in their SCM project is discussed, together with the process of how Seagate has created a paradigm shift towards a new culture of teamwork-based collaboration.

Delivery and stability of antisense oligonucleotide conjugates in vitro

The efficacy of antisense oligonucleotide (ODN) therapy is dependent on four major parameters: delivery to cells, intracellular stability and localisation and efficient action at the target site.The aim of this project was to study the delivery of ODNs to macrophages and to assess the stability of two ODN conjugates, in vitro. The first conjugate aimed to improve uptake of ODNs via mannose receptor mediated delivery, the second investigated the improved delivery of ODN conjugates via non-specific lipophilic interaction with the cell membrane. A mono-mannose phosphoramidite derivative was designed and synthesised and a mono-mannose ODN conjugate synthesised by standard phosphoramidite chemistry. Delivery of this conjugate was enhanced to RAW264.7 and J774 macrophage cell lines via a mechanism of receptor mediated endocytosis. The delivery of three lipophilic ODN conjugates, cholesterol (cholhex), 16-carbon alkyl chain (C16) and hexa-ethylene glycol (HEG) moieties and an unconjugated ODN were assessed in RAW264.7 macrophages. All three conjugates increased the lipophilicity of the ODN as assessed from partition coefficient data. Both the cholhex and unconjugated ODNs were found to have higher degrees of cellular association than the C16 and HEG conjugates. Cellular uptake studies implicated internalisation of these ODNs by an adsorptive endocytosis mechanism. Following endocytosis, ODNs must remain stable during their residence in endosomal/lysosomal compartments prior to exiting and exerting their biological action in either the cytosol or nucleus. Assessment of in vitro stability in a lysosomal extract revealed the cholhex conjugate and unconjugated ODNs to have a longer half-life than the C16 and HEG conjugated ODNs, highlighting the influence of conjugate moieties on lysosomal stability. The effects of base composition and length on stability in a lysosomal extract revealed the longest half-life for homo-cytidine ODNs and ODNs over 20 nucleotides in length. These studies suggest that the above conjugates can enhance cellular association and delivery of antisense ODNs to cultured macrophages. This may lead to their use in treating disorders such as HIV infection, which affects this cell type.

Novel biodegradable fibres for applications in tissue engineering and drug delivery

The preparation and characterisation of novel biodegradable polymer fibres for application in tissue engineering and drug delivery are reported. Poly(e-caprolactone) (PCL) fibres were produced by wet spinning from solutions in acetone under low shear (gravity flow) conditions. The tensile strength and stiffness of as-spun fibres were highly dependent on the concentration of the spinning solution. Use of a 6% w/v solution resulted in fibres having strength and stiffness of 1.8 MPa and 0.01 GPa respectively, whereas these values increased to 9.9 MPa and 0.1 GPa when fibres were produced from 20% w/v solutions. Cold drawing to an extension of 500% resulted in further increases in fibre strength (up to 50 MPa) and stiffness (0.3 GPa). Hot drawing to 500% further increased the fibre strength (up to 81 MPa) and stiffness (0.5 GPa). The surface morphology of as-spun fibres was modified, to yield a directional grooved pattern by drying in contact with a mandrel having a machined topography characterised by a peak-peak separation of 91 mm and a peak height of 30 mm. Differential scanning calorimetery (DSC) analysis of as-spun fibres revealed the characteristic melting point of PCL at around 58°C and a % crystallinity of approximately 60%. The biocompatibility of as-spun fibres was assessed using cell culture. The number of attached 3T3 Swiss mouse fibroblasts, C2C12 mouse myoblasts and human umbilical vein endothelial cells (HUVECs) on as-spun, 500% cold drawn, and gelatin coated PCL fibres were observed. The results showed that the fibres promoted cell proliferation for 9 days in cell culture and was slightly lower than on tissue culture plastic. The morphology of all cell lines was assessed on the various PCL fibres using scanning electron microscopy. The cell function of HUVECs growing on the as-spun PCL fibres was evaluated. The ability HUVECs to induce an immune response when stimulated with lipopolysaccaride (LPS) and thereby to increase the amount of cell surface receptors was assessed by flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR). The results showed that PCL fibres did not inhibit this function compared to TCP. As-spun PCL fibres were loaded with 1 % ovine albumin (OVA) powder, 1% OVA nanoparticles and 5% OVA nanoparticles by weight and the protein release was assessed in vitro. PCL fibres loaded with 1 % OVA powder released 70%, 1% OVA nanoparticle released 60% and the 5% OVA nanoparticle released 25% of their protein content over 28 days. These release figures did not alter when the fibres were subjected to lipase enzymatic degradation. The OVA released was examined for structural integrity by SDS-PAGE. This showed that the protein molecular weight was not altered after incorporation into the fibres. The bioactivity of progesterone was assessed following incorporation into PCL fibres. Results showed that the progesterone released had a pronounced effect on MCF-7 breast epithelial cells, inhibiting their proliferation. The PCL fibres display high fibre compliance, a potential for controlling the fibre surface architecture to promote contact guidance effects, favorable proliferation rate of fibroblasts, myoblasts and HUVECs and the ability to release pharmaceuticals. These properties recommended their use for 3-D scaffold production in soft tissue engineering and the fibres could also be exploited for controlled presentation and release of biopharmaceuticals such as growth factors.

Polymer-peptide conjugate hydrogels:towards controlled drug delivery

Peptide-based materials exhibit remarkable supramolecular self-assembling behavior, owing to their overwhelming propensity to from hierarchical structures from a-helices and ß-sheets. Coupling a peptide sequence to a synthetic polymer chain allows greater control over the final physical properties of the supermolecular material. So-called ‘polymer-peptide conjugates’ can be used to create biocompatible hydrogels which are held together by reversible physical interactions. Potentially, the hydrogels can be loaded with aqueous-based drug molecules, which can be injected into targeted sites in the body if they can exhibit a gel-sol-gel transition under application and removal of a shear force. In this review, we introduce this topic to readers new to the field of polymer-peptide conjugates, discussing common synthetic strategies and their self-assembling behavior. The lack of examples of actual drug delivery applications from polymer-peptide conjugates is highlighted in an attempt to incite progress in this area.

Local delivery of the KCa3.1 blocker, TRAM-34, prevents acute angioplasty-induced coronary smooth muscle phenotypic modulation and limits stenosis

Objective-We previously demonstrated that upregulation of intermediate-conductance Ca2+ -activated K+ channels (KCa 3.1) is necessary for mitogen-induced phenotypic modulation in isolated porcine coronary smooth muscle cells (SMCs). The objective of the present study was to determine the role of KCa3.1 in the regulation of coronary SMC phenotypic modulation in vivo using a swine model of postangioplasty restenosis. Methods and Results-Balloon angioplasty was performed on coronary arteries of swine using either noncoated or balloons coated with the specific KCa3.1 blocker TRAM-34. Expression of KCa3.1, c-jun, c-fos, repressor element-1 silencing transcription factor (REST), smooth muscle myosin heavy chain (SMMHC), and myocardin was measured using qRT-PCR in isolated medial cells 2 hours and 2 days postangioplasty. KCa3.1, c-jun, and c-fos mRNA levels were increased 2 hours postangioplasty, whereas REST expression decreased. SMMHC expression was unchanged at 2 hours, but decreased 2 days postangioplasty. Use of TRAM-34 coated balloons prevented KCa3.1 upregulation and REST downregulation at 2 hours, SMMHC and myocardin downregulation at 2 days, and attenuated subsequent restenosis 14 and 28 days postangioplasty. Immunohistochemical analysis demonstrated corresponding changes at the protein level. Conclusion-Blockade of KCa3.1 by delivery of TRAM-34 via balloon catheter prevented smooth muscle phenotypic modulation and limited subsequent restenosis. © 2008 American Heart Association, Inc.

Investigating local delivery by road to retail and non-retail customers in the UK logistics sector

Over recent years, hub-and-spoke distribution techniques have attracted widespread research attention. Despite there being a growing body of literature in this area there is less focus on the spoke-terminal element of the hub-and-spoke system as being a key component in the overall service received by the end-user. Current literature is highly geared towards discussing bulk optimization of freight units rather than to the more discrete and individualistic profile characteristics of shared-user Less-than-truckload (LTL) freight. In this paper, a literature review is presented to review the role hub-and-spoke systems play in meeting multi-profile customer demands, particularly in developing sectors with more sophisticated needs, such as retail. The paper also looks at the use of simulation technology as a suitable tool for analyzing spoke-terminal operations within developing hub-and spoke systems.

A strategy formulation process for the delivery of technology enabled service delivery systems

The Product Service Systems, servitization, and Service Science literature continues to grow as organisations seek to protect and improve their competitive position. The potential of technology applications to deliver service delivery systems facilitated by the ability to make real time decisions based upon ‘in the field’ performance is also significant. Research identifies four key questions to be addressed. Namely: how far along the servitization continuum should the organisation go in a single strategic step? Does the organisation have the structure and infrastructure to support this transition? What level of condition monitoring should it employ? Is the product positioned correctly in the value chain to adopt condition monitoring technology? Strategy consists of three dimensions, namely content, context, and process. The literature relating to PSS, servitization, and strategy all discuss the concepts relative to content and context but none offer a process to deliver an aligned strategy to deliver a service delivery system enabled by condition based management. This paper presents a tested iterative strategy formulation methodology which is the result of a structured development programme.

Supply chain "mega-trends":current status and future trends

The supply chain management (SCM) concept has become embedded in the thinking of many organisations in recent years. Originally introduced by management consultants in the early 1980s, SCM has a strong focus on integration of processes across functions within firms, as well as between the organisations that comprise the wider extended enterprise. There is a significant body of research to support the notion that the consistent delivery of value to customers is predicated on higher levels of intra-firm and inter-firm integration. Putting the supply chain integration (SCI) concept into practice is critically dependent on the ability of firms to manage material, money and information flows in a holistic manner. It also depends on the way in which relationships between key supply chain actors are managed. This article explores the “mega-trends” that are evident across most sectors and which have a potentially significant impact on the ability of organisations to put SCM theory into practice. The late Don Bowersox and his colleagues from Michigan State University introduced the idea of supply chain “mega-trends” over a decade ago in their widely cited article in the Journal of Business Logistics (Bowersox et al., 2000). This article explores the current status of these “mega-trends” in an Irish context based on research being undertaken at the National Institute for Transport and Logistics (NITL). It also identifies some key factors that are likely to impact upon progress in these key areas in the medium term.