2,973 research outputs found

    Impact of supply chain actor citizenship behavior on supply chain learning processes

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    Critical evaluation of early literature into supply chain learning indicates lack of research into the impact of supply chain actor citizenship behavior on supply chain learning processes. Therefore, this study explores the impact of supply chain actor citizenship behavior impact on supply chain learning processes. The study uses constructivist epistemology, interpretative theoretical perspective, case study research methodology and grounded theory thematic technique in data analysis. Findings of the study indicate that different elements of the supply chain actor citizenship behavior concept are connected to different levels of supply chain learning processes. Self-development is found to have an impact on intuition process, helping behavior is found to have an impact on interpretation process, tolerance is found to have an impact on integration process and constructiveness is found to have an impact on institutionalization process. An original contribution to theory includes extending organizational learning theory and citizenship behavior concept to supply chain context. And practitioners are recommended to explore dynamics of self-development, helping behavior, tolerance, and constructiveness on enhancing supply chain learning processes.  </p

    Achieving near-zero carbon dioxide emissions from energy use: The case of Sri Lanka

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    Signatories to the Paris Agreement are to achieve net zero Green House Gas (GHG) emissions during the half-century to pursue the efforts limiting global average temperature increase by 2 °C compared to pre-industrial levels. This study models ambitious to challenging scenarios involving energy demand and supply side actions for energy system transition toward net-zero for Sri Lanka. To analyze these scenarios a least cost optimization-based bottom-up type energy system model was developed from 2015 to 2050. A Business-as-usual (BAU) scenario and four countermeasure (CM) scenarios termed Plausible, Ambitious, Challenging, and Stringent were developed. Four different carbon tax rates were used to fathom the level of carbon tax needed to achieve net-zero emissions. The CM scenarios were formulated considering different technology options and policy measures such as the diffusion of efficient technologies, availability of renewable energy sources, use of cleaner fuels, the introduction of nuclear and carbon capture and storage technologies, and green hydrogen for power generation. The result of this study reveals that the stringent scenario which includes aggressive policy measures in both the energy supply and demand sectors, such as nuclear, and renewable energy for power generation, diffusion of efficient Enduse devices, fuel switching, including the introduction of electric cars, and increased share for public transport achieves the near carbon-neutral scenario at a carbon tax trajectory of 32 US/tCO2in2020and562US/tCO2 in 2020 and 562US/tCO2 in 2050. The Net Energy Import Dependency (NEID) of the country decreases to 13 % in 2050 compared to that of the BAU scenario (65 %) under the near carbon neutral scenario, which is a positive sign from the energy security perspective

    Pathological Angiogenesis Requires Syndecan-4 for Efficient VEGFA-Induced VE-Cadherin Internalization

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    Objective: VEGFA (Vascular endothelial growth factor A) and its receptor VEGFR2 (vascular endothelial growth factor receptor 2) drive angiogenesis in several pathologies, including diabetic retinopathy, wet age-related macular degeneration, and cancer. Studies suggest roles for HSPGs (heparan sulfate proteoglycans) in this process, although the nature of this involvement remains elusive. Here, we set to establish the role of the HSPG SDC4 (syndecan-4) in pathological angiogenesis. Approach and Results: We report that angiogenesis is impaired in mice null for SDC4 in models of neovascular eye disease and tumor development. Our work demonstrates that SDC4 is the only SDC whose gene expression is upregulated during pathological angiogenesis and is selectively enriched on immature vessels in retinas from diabetic retinopathy patients. Combining in vivo and tissue culture models, we identified SDC4 as a downstream mediator of functional angiogenic responses to VEGFA. We found that SDC4 resides at endothelial cell junctions, interacts with vascular endothelial cadherin, and is required for its internalization in response to VEGFA. Finally, we show that pathological angiogenic responses are inhibited in a model of wet age-related macular degeneration by targeting SDC4. Conclusions: We show that SDC4 is a downstream mediator of VEGFA-induced vascular endothelial cadherin internalization during pathological angiogenesis and a potential target for antiangiogenic therapies

    Pathological Angiogenesis Requires Syndecan-4 for Efficient VEGFA-Induced VE-Cadherin Internalization.

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    Objective: VEGFA (Vascular endothelial growth factor A) and its receptor VEGFR2 (vascular endothelial growth factor receptor 2) drive angiogenesis in several pathologies, including diabetic retinopathy, wet age-related macular degeneration, and cancer. Studies suggest roles for HSPGs (heparan sulfate proteoglycans) in this process, although the nature of this involvement remains elusive. Here, we set to establish the role of the HSPG SDC4 (syndecan-4) in pathological angiogenesis. / Approach and Results: We report that angiogenesis is impaired in mice null for SDC4 in models of neovascular eye disease and tumor development. Our work demonstrates that SDC4 is the only SDC whose gene expression is upregulated during pathological angiogenesis and is selectively enriched on immature vessels in retinas from diabetic retinopathy patients. Combining in vivo and tissue culture models, we identified SDC4 as a downstream mediator of functional angiogenic responses to VEGFA. We found that SDC4 resides at endothelial cell junctions, interacts with vascular endothelial cadherin, and is required for its internalization in response to VEGFA. Finally, we show that pathological angiogenic responses are inhibited in a model of wet age-related macular degeneration by targeting SDC4. / Conclusions: We show that SDC4 is a downstream mediator of VEGFA-induced vascular endothelial cadherin internalization during pathological angiogenesis and a potential target for antiangiogenic therapies

    Immunohistochemical detection of Claudin low breast cancer; which subcellular level to be assessed?

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    Objectives: Claudin low breast cancers are often high grade, triple negative tumours with poor prognosis.  They are identified at genetic level and are not diagnosed routinely by immunohistochemistry. The objective was to determine the best subcellular level to detect Claudin low breast cancer by immunohistochemistry, in terms of their histopathological prognostic features.Methods: This cross sectional study included all archival breast cancer tissue collected up to December 2015 in our unit. Tissue microarrays (TMA) were constructed using 23 breast cancer cores with a diameter of 2mm, in each TMA. TMAs were immunohistochemically stained for Claudin 3 expression and was scored as; no staining=0, weak staining=1, moderate staining=2 and strong staining=3, separately for membrane, cytoplasmic and nuclear staining. A score <2 was considered Claudin low and analysed against the histopathological prognostic features of the breast cancer.Results: A total of 546 breast cancers were assessed. Claudin low expression was identified at cytoplasmic, membrane and nuclear level in 74.9%, 74.5% and 42% of breast cancers respectively. Low nuclear expression of Claudin 3 was associated with high grade (p=0.028), Nottingham Prognostic Index of >3.4 (p=0.028), ER and PR negative (p<0.001) and HER 2 negative (p=0.013) tumours while low membrane staining was associated with low grade (p=0.038), HER 2 negative (p<0.001) breast cancers. Low cytoplasmic staining was associated with HER 2 negative breast cancer only (p=0.002).Conclusions: Nuclear staining for Claudin should be assessed to identify Claudin low breast cancer by immunohistochemistry as it significantly associates with most of the Claudin low breast cancer characteristics

    The Chagos Islands cases: the empire strikes back

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    Good governance requires the accommodation of multiple interests in the cause of decision making. However, undue regard for particular sectional interests can take their toll upon public faith in government administration. Historically, broad conceptions of the good of the commonwealth were employed to outweigh the interests of groups that resisted colonisation. In the decision making of the British Empire, the standard approach for justifying the marginalisation of the interests of colonised groups was that they were uncivilised and that particular hardships were the price to be paid for bringing to them the imperial dividend of industrial society. It is widely assumed that with the dismantling of the British Empire, such impulses and their accompanying jurisprudence became a thing of the past. Even as decolonisation proceeded apace after the Second World War, however, the United Kingdom maintained control of strategically important islands with a view towards sustaining its global role. In an infamous example from this twilight period of empire, in the 1960s imperial interests were used to justify the expulsion of the Chagos islanders from the British Indian Ocean Territory (BIOT). Into the twenty-first century, this forced elision of the UK’s interests with the imperial “common good” continues to take centre stage in courtroom battles over the islanders’ rights, being cited before domestic and international tribunals in order to maintain the Chagossians’ exclusion from their homeland. This article considers the new jurisprudence of imperialism which has emerged in a string of decisions which have continued to marginalise the Chagossians’ interests

    A Study of the Natural History of Vitreomacular Traction Syndrome by OCT

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    PURPOSE: To examine the natural history of vitreomacular traction syndrome (VMTS) in the absence of other ocular comorbidities. DESIGN: Retrospective clinical case series. PARTICIPANTS: A total of 183 eyes of 159 patients diagnosed with VMTS with no other ocular comorbidity. METHODS: Patients with VMTS were identified from an OCT database at Moorfields Eye Hospital, London. Sequential OCT scans and patient notes were reviewed over a minimum period of 6 months. Data collected included patient demographics, best-corrected visual acuity, and OCT features of vitreomacular adhesion. Contingency tests and binary logistic modeling were used to identify baseline predictors of stability and progression. MAIN OUTCOME MEASURES: The rates of spontaneous resolution (defined by release of traction), progression to full-thickness macular hole, and surgical intervention were analyzed. RESULTS: Presenting visual acuity was 0.3±0.3 logMAR units. The mean length of follow-up was 17.4±12.1 months. During this period, VMTS persisted in 60% and resolved in 20% (occurring on average at 15 months). Of the remainder, 12% developed a macular hole and 8% elected to proceed with surgery for symptoms. Focal adhesion <1500 Όm was present in 87%. A premacular membrane with macular pucker (PMM) was present in 20%. With persistent VMTS, vision and central foveal thickness remained unchanged. The relative risk of resolution increased in those cases with better presenting visual acuities, lesser foveal thicknesses, and no associated PMMs; vision significantly improved in those cases with resolution. CONCLUSIONS: VMTS persists in the majority of patients but despite this, visual acuities did not deteriorate significantly over the study period unless patients developed a full-thickness macular hole or required surgical intervention for symptoms. Resolution spontaneously occurred in 20%, with an improvement in vision
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