Clusters and supply chain management: challenges and obstacles

Purpose: This paper provides an insight into cluster supply chain (CSC) management by identifying challenges and obstacles in the design, implementation and improvement of CSC. This evaluation aims to propose future research directions for the management of CSC. Research Approach: A systematic review of published research on CSC management between 2006 and 2013 is conducted in order to round up previous research in this area and identify the gaps in the design, implementation and management of CSC; up on which the paper closes with a proposed agenda for future work. Findings and Originality: There is a limited understanding of the supply chain cluster concept and the implementation of its practices in addition to the lack of studies that focused on how to model, manage and improve the performance of CSC. Therefore, this paper would contribute to knowledge by providing an insight into CSC management and identifying future research directions for developing SC cluster theories in order to maximize the integration of supply chain and accordingly improving the performance of firms. Research Impact: A limited number of studies have been conducted to demonstrate the potential impact of CSC. The previous research did not provide a comprehensive review focusing on the evolution and the development of CSC idea. The review in this paper will summarise the research up to now in CSC area in order to identify challenges and obstacles in the design, implementation and improvement of CSC and propose future research directions. Practical Impact: This paper helps companies to understand benefits that can be raised from creating CSC and gives them directions for improving their capabilities to create CSC and select SC partners, which consequently help in increasing their competitiveness in terms of enhancing performance and increasing sustainability

Quantitative proteomic analysis of sphere-forming stem-like oral cancer cells.

IntroductionThe purpose of this study is to identify target proteins that may play important functional roles in oral cancer stem-like cells (CSCs) using mass spectrometry-based quantitative proteomics.MethodsSphere-formation assays were performed on highly invasive UM1 and lowly invasive UM2 oral cancer cell lines, which were derived from the same tongue squamous cell carcinoma, to enrich CSCs. Quantitative proteomic analysis of CSC-like and non-CSC UM1 cells was carried out using tandem mass tagging and two-dimensional liquid chromatography with Orbitrap mass spectrometry.ResultsCSC-like cancer cells were found to be present in the highly invasive UM1 cell line but absent in the lowly invasive UM2 cell line. Stem cell markers SOX2, OCT4, SOX9 and CD44 were up-regulated, whereas HIF-1 alpha and PGK-1 were down-regulated in CSC-like UM1 cells versus non-CSC UM1 cells. Quantitative proteomic analysis indicated that many proteins in cell cycle, metabolism, G protein signal transduction, translational elongation, development, and RNA splicing pathways were differentially expressed between the two cell phenotypes. Both CREB-1-binding protein (CBP) and phosphorylated CREB-1 were found to be significantly over-expressed in CSC-like UM1 cells.ConclusionsCSC-like cells can be enriched from the highly invasive UM1 oral cancer cell line but not from the lowly invasive UM2 oral cancer cell line. There are significant proteomic alterations between CSC-like and non-CSC UM1 cells. In particular, CBP and phosphorylated CREB-1 were significantly up-regulated in CSC-like UM1 cells versus non-CSC UM1 cells, suggesting that the CREB pathway is activated in the CSC-like cells

Operation and control of a current source converter series tapping of an LCC-HVDC link for integration of offshore wind power plants

This work presents a series tapping station for integrating Offshore Wind Power Plants (OWPP) into a (Line Commutated Converter High Voltage Direct Current) LCC-HVDC transmission system. The tapping station allows to integrate wind power resources without building a new HVDC link and it is based on a Current Source Converter (CSC). However, the CSC requires a minimum DC current to extract the power coming from the OWPP which may not be guaranteed depending on the power conditions of the HVDC corridor. For this reason, this paper proposes a coordinated operation and control of the CSC and the OWPP. A steady-state analysis is performed to determine the appropriate AC voltage level of the CSC. A power reduction algorithm is presented to limit power extraction during a reduction in the current of the HVDC transmission system and under loss of communications between the CSC and the OWPP. The proposed algorithm and the performance of the system are validated through simulation results.Peer ReviewedPostprint (author's final draft

YB-1 dependent oncolytic adenovirus efficiently inhibits tumor growth of glioma cancer stem like cells

Background: The brain cancer stem cell (CSC) model describes a small subset of glioma cells as being responsible for tumor initiation, conferring therapy resistance and tumor recurrence. In brain CSC, the PI3-K/AKT and the RAS/mitogen activated protein kinase (MAPK) pathways are found to be activated. In consequence, the human transcription factor YB-1, knowing to be responsible for the emergence of drug resistance and driving adenoviral replication, is phosphorylated and activated. With this knowledge, YB-1 was established in the past as a biomarker for disease progression and prognosis. This study determines the expression of YB-1 in glioblastoma (GBM) specimen in vivo and in brain CSC lines. In addition, the capacity of Ad-Delo3-RGD, an YB-1 dependent oncolytic adenovirus, to eradicate CSC was evaluated both in vitro and in vivo. Methods: YB-1 expression was investigated by immunoblot and immuno-histochemistry. In vitro, viral replication as well as the capacity of Ad-Delo3-RGD to replicate in and, in consequence, to kill CSC was determined by real-time PCR and clonogenic dilution assays. In vivo, Ad-Delo3-RGD-mediated tumor growth inhibition was evaluated in an orthotopic mouse GBM model. Safety and specificity of Ad-Delo3-RGD were investigated in immortalized human astrocytes and by siRNA-mediated downregulation of YB-1. Results: YB-1 is highly expressed in brain CSC lines and in GBM specimen. Efficient viral replication in and virus-mediated lysis of CSC was observed in vitro. Experiments addressing safety aspects of Ad-Delo3-RGD showed that (i) virus production in human astrocytes was significantly reduced compared to wild type adenovirus (Ad-WT) and (ii) knockdown of YB-1 significantly reduced virus replication. Mice harboring othotopic GBM developed from a temozolomide (TMZ)-resistant GBM derived CSC line which was intratumorally injected with Ad-Delo3-RGD survived significantly longer than mice receiving PBS-injections or TMZ treatment. Conclusion: The results of this study supported YB-1 based virotherapy as an attractive therapeutic strategy for GBM treatment which will be exploited further in multimodal treatment concepts

On the conservation of spin currents in spin-orbit coupled systems

Applying the Gordon-decomposition-like technique, the convective spin current (CSC) is extracted from the total angular-momentum current. The CSC describes the transport properties of the electron spin and is conserved in the relativistic quantum mechanics approach where the spin-orbit coupling has been intrinsically taken into account. Arrestingly, in the presence of external electromagnetic field, the component of the convective spin along the field remain still conserved. This conserved CSC is also derived for the first time in the nonrelativistic limit using the Foldy-Wouthuysen transformation.Comment: 5 pages, RevTeX

Anti-proliferative but not anti-angiogenic tyrosine kinase inhibitors enrich for cancer stem cells in soft tissue sarcoma.

BackgroundIncreasing studies implicate cancer stem cells (CSCs) as the source of resistance and relapse following conventional cytotoxic therapies. Few studies have examined the response of CSCs to targeted therapies, such as tyrosine kinase inhibitors (TKIs). We hypothesized that TKIs would have differential effects on CSC populations depending on their mechanism of action (anti-proliferative vs. anti-angiogenic).MethodsWe exposed human sarcoma cell lines to sorafenib, regorafenib, and pazopanib and assessed cell viability and expression of CSC markers (ALDH, CD24, CD44, and CD133). We evaluated survival and CSC phenotype in mice harboring sarcoma metastases after TKI therapy. We exposed dissociated primary sarcoma tumors to sorafenib, regorafenib, and pazopanib, and we used tissue microarray (TMA) and primary sarcoma samples to evaluate the frequency and intensity of CSC markers after neoadjuvant therapy with sorafenib and pazopanib. Parametric and non-parametric statistical analyses were performed as appropriate.ResultsAfter functionally validating the CSC phenotype of ALDHbright sarcoma cells, we observed that sorafenib and regorafenib were cytotoxic to sarcoma cell lines (P < 0.05), with a corresponding 1.4 - 2.8 fold increase in ALDHbright cells from baseline (P < 0.05). In contrast, we observed negligible effects on viability and CSC sub-populations with pazopanib. At low doses, there was progressive CSC enrichment in vitro after longer term exposure to sorafenib although the anti-proliferative effects were attenuated. In vivo, sorafenib improved median survival by 11 days (P < 0.05), but enriched ALDHbright cells 2.5 - 2.8 fold (P < 0.05). Analysis of primary human sarcoma samples revealed direct cytotoxicity following exposure to sorafenib and regorafenib with a corresponding increase in ALDHbright cells (P < 0.05). Again, negligible effects from pazopanib were observed. TMA analysis of archived specimens from sarcoma patients treated with sorafenib demonstrated significant enrichment for ALDHbright cells in the post-treatment resection specimen (P < 0.05), whereas clinical specimens obtained longitudinally from a patient treated with pazopanib showed no enrichment for ALDHbright cells (P > 0.05).ConclusionsAnti-proliferative TKIs appear to enrich for sarcoma CSCs while anti-angiogenic TKIs do not. The rational selection of targeted therapies for sarcoma patients may benefit from an awareness of the differential impact of TKIs on CSC populations