858 research outputs found

    Seeking legitimacy through CSR: Institutional Pressures and Corporate Responses of Multinationals in Sri Lanka

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    Arguably, the corporate social responsibility (CSR) practices of multinational enterprises (MNEs) are influenced by a wide range of both internal and external factors. Perhaps most critical among the exogenous forces operating on MNEs are those exerted by state and other key institutional actors in host countries. Crucially, academic research conducted to date offers little data about how MNEs use their CSR activities to strategically manage their relationship with those actors in order to gain legitimisation advantages in host countries. This paper addresses that gap by exploring interactions between external institutional pressures and firm-level CSR activities, which take the form of community initiatives, to examine how MNEs develop their legitimacy-seeking policies and practices. In focusing on a developing country, Sri Lanka, this paper provides valuable insights into how MNEs instrumentally utilise community initiatives in a country where relationship-building with governmental and other powerful non-governmental actors can be vitally important for the long-term viability of the business. Drawing on neo-institutional theory and CSR literature, this paper examines and contributes to the embryonic but emerging debate about the instrumental and political implications of CSR. The evidence presented and discussed here reveals the extent to which, and the reasons why, MNEs engage in complex legitimacy-seeking relationships with Sri Lankan institutions

    Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

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    Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

    Influence of socioeconomic factors on medically unnecessary ambulance calls

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    <p>Abstract</p> <p>Background</p> <p>Unnecessary ambulance use has become a socioeconomic problem in Japan. We investigated the possible relations between socioeconomic factors and medically unnecessary ambulance calls, and we estimated the incremental demand for unnecessary ambulance use produced by socioeconomic factors.</p> <p>Methods</p> <p>We conducted a self-administered questionnaire-based survey targeting residents of Yokohama, Japan. The questionnaire included questions pertaining to socioeconomic characteristics, dichotomous choice method questions pertaining to ambulance calls in hypothetical nonemergency situations, and questions on the city's emergency medical system. The probit model was used to analyze the data.</p> <p>Results</p> <p>A total of 2,029 out of 3,363 targeted recipients completed the questionnaire (response rate, 60.3%). Probit regression analyses showed that several demographic and socioeconomic factors influence the decision to call an ambulance. Male respondents were more apt than female respondents to state that they would call an ambulance in nonemergency situations (p < 0.05). Age was an important factor influencing the hypothetical decision to call an ambulance (p < 0.05); elderly persons were more apt than younger persons to state that they would call an ambulance. Possession of a car and hesitation to use an ambulance negatively influenced the hypothetical decision to call an ambulance (p < 0.05). Persons who do not have a car were more likely than those with a car to state that they would call an ambulance in unnecessary situations.</p> <p>Conclusion</p> <p>Results of the study suggest that several socioeconomic factors, i.e., age, gender, household income, and possession of a car, influence a person's decision to call an ambulance in nonemergency situations. Hesitation to use an ambulance and knowledge of the city's primary emergency medical center are likely to be important factors limiting ambulance overuse. It was estimated that unnecessary ambulance use is increased approximately 10% to 20% by socioeconomic factors.</p

    Improved precision on the experimental E0 decay branching ratio of the Hoyle state

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    Stellar carbon synthesis occurs exclusively via the 3α3\alpha process, in which three α\alpha particles fuse to form 12^{12}C in the excited Hoyle state, followed by electromagnetic decay to the ground state. The Hoyle state is above the α\alpha threshold, and the rate of stellar carbon production depends on the radiative width of this state. The radiative width cannot be measured directly, and must instead be deduced by combining three separately measured quantities. One of these quantities is the E0E0 decay branching ratio of the Hoyle state, and the current 1010\% uncertainty on the radiative width stems mainly from the uncertainty on this ratio. The E0E0 branching ratio was deduced from a series of pair conversion measurements of the E0E0 and E2E2 transitions depopulating the 02+0^+_2 Hoyle state and 21+2^+_1 state in 12^{12}C, respectively. The excited states were populated by the 12^{12}C(p,p)(p,p^\prime) reaction at 10.5 MeV beam energy, and the pairs were detected with the electron-positron pair spectrometer, Super-e, at the Australian National University. The deduced branching ratio required knowledge of the proton population of the two states, as well as the alignment of the 21+2^+_1 state in the reaction. For this purpose, proton scattering and γ\gamma-ray angular distribution experiments were also performed. An E0E0 branching ratio of ΓπE0/Γ=8.2(5)×106\Gamma^{E0}_{\pi}/\Gamma=8.2(5)\times10^{-6} was deduced in the current work, and an adopted value of ΓπE0/Γ=7.6(4)×106\Gamma^{E0}_{\pi}/\Gamma=7.6(4)\times10^{-6} is recommended based on a weighted average of previous literature values and the new result. The new recommended value for the E0E0 branching ratio is about 14% larger than the previous adopted value of ΓπE0/Γ=6.7(6)×106\Gamma^{E0}_{\pi}/\Gamma=6.7(6)\times10^{-6}, while the uncertainty has been reduced from 9% to 5%.Comment: Accepted for publication as a Regular Article in Phys. Rev. C on July 29 202

    Focal Adhesion Kinase contributes to insulin-induced actin reorganization into a mesh harboring Glucose transporter-4 in insulin resistant skeletal muscle cells

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    <p>Abstract</p> <p>Background</p> <p>Focal Adhesion Kinase (FAK) is recently reported to regulate insulin resistance by regulating glucose uptake in C2C12 skeletal muscle cells. However, the underlying mechanism for FAK-mediated glucose transporter-4 translocation (Glut-4), responsible for glucose uptake, remains unknown. Recently actin remodeling was reported to be essential for Glut-4 translocation. Therefore, we investigated whether FAK contributes to insulin-induced actin remodeling and harbor Glut-4 for glucose transport and whether downregulation of FAK affects the remodeling and causes insulin resistance.</p> <p>Results</p> <p>To address the issue we employed two approaches: gain of function by overexpressing FAK and loss of function by siRNA-mediated silencing of FAK. We observed that overexpression of FAK induces actin remodeling in skeletal muscle cells in presence of insulin. Concomitant to this Glut-4 molecules were also observed to be present in the vicinity of remodeled actin, as indicated by the colocalization studies. FAK-mediated actin remodeling resulted into subsequent glucose uptake via PI3K-dependent pathway. On the other hand FAK silencing reduced actin remodeling affecting Glut-4 translocation resulting into insulin resistance.</p> <p>Conclusion</p> <p>The data confirms that FAK regulates glucose uptake through actin reorganization in skeletal muscle. FAK overexpression supports actin remodeling and subsequent glucose uptake in a PI3K dependent manner. Inhibition of FAK prevents insulin-stimulated remodeling of actin filaments resulting into decreased Glut-4 translocation and glucose uptake generating insulin resistance. To our knowledge this is the first study relating FAK, actin remodeling, Glut-4 translocation and glucose uptake and their interrelationship in generating insulin resistance.</p

    Solenogam: A new detector array for γ-ray and conversion-electron spectroscopy of long-lived states in fusion-evaporation products

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    A new detector array, Solenogam, has been developed at the Australian National University Heavy Ion Accelerator Facility. Coupled initially to the SOLITAIRE 6.5 T, gas-filled, solenoidal separator, and later to an 8 T solenoid, the system enables the study of long-lived nuclear states through -ray and conversion-electron spectroscopy in a low-background environment. The detector system is described and results from the commissioning experiments are presented.The authors are grateful to the academic and technical staff of the Department of Nuclear Physics (Australian National University) and the Heavy Ion Accelerator Facility for their continued support. This re- search was supported by the Australian Research Council through grant numbers FT100100991, DP120101417, DP14102986, and DP140103317. M.S.M.G., A.A., B.J.C., J.T.H.D., T.J.G., B.Q.L., and T.P. acknowledge the support of the Australian Government Research Training Program. Support for the ANU Heavy Ion Accelerator Facility operations through the Australian National Collaborative Research Infrastructure Strategy (NCRIS) program is acknowledge

    Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

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    Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

    Genetic Polymorphism in a VEGF-Independent Angiogenesis Gene ANGPT1 and Overall Survival of Colorectal Cancer Patients after Surgical Resection

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    Background The VEGF-independent angiogenic signaling plays an important role in the development of colorectal cancer (CRC). However, its implication in the clinical outcome of CRC has not been reported. This study aimed to investigate the association between genetic variations in several major VEGF-independent signaling pathway genes and the overall survival of CRC patients. Methods Seven single nucleotide polymorphisms (SNPs) in four important VEGF-independent angiogenic genes (ANGPT1, AMOT, DLL4 and ENG) were genotyped in a Chinese population with 408 CRC patients. Results One SNP, rs1954727 in ANGPT1, was significantly associated with CRC overall survival. Compared to patients with the homozygous wild-type genotype of rs1954727, those with heterozygous and homozygous variant genotypes exhibited a favorable overall survival with a hazard ratio (HR) of 0.89 (95% confidence interval [CI] 0.55–1.43, P = 0.623), and 0.32 (95% CI 0.15–0.71, P = 0.005), respectively (P trend = 0.008). In stratified analysis, this association remained significant in patients receiving chemotherapy (P trend = 0.012), but not in those without chemotherapy. We further evaluated the effects of chemotherapy on CRC survival that was stratified by rs1954727 genotypes. We found that chemotherapy resulted in a significantly better overall survival in the CRC patients (HR = 0.44, 95% CI 0.26–0.75, P = 0.002), which was especially prominent in those patients with the heterozygous genotype of rs1954727 (HR = 0.45, 95%CI 0.22–0.92, P = 0.028). Conclusion Our data suggest that rs1954727 in ANGPT1 gene might be a prognostic biomarker for the overall survival of CRC patients, especially in those receiving chemotherapy, a finding that warrants validation in larger independent populations

    Cell cycle regulation by the Wee1 Inhibitor PD0166285, Pyrido [2,3-d] pyimidine, in the B16 mouse melanoma cell line

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    BACKGROUND: Wee1 kinase plays a critical role in maintaining G2 arrest through its inhibitory phosphorylation of cdc2. In previous reports, a pyridopyrimidine molecule PD0166285 was identified to inhibit Wee1 activity at nanomolar concentrations. This G2 checkpoint abrogation by PD0166285 was demonstrated to kill cancer cells, there at a toxic highest dose of 0.5 μM in some cell lines for exposure periods of no longer than 6 hours. The deregulated cell cycle progression may have ultimately damaged the cancer cells. We herein report one of the mechanism by which PD0166285 leads to cell death in the B16 mouse melanoma cell line. METHODS: Tumor cell proliferation was determined by counting cell numbers. Cell cycle distribution was determined by flow cytometry. Morphogenesis analysis such as microtubule stabilization, Wee1 distribution, and cyclin B location were observed by immunofluorescence confocal microscopy. An immunoblot analysis of cdc2-Tyr15, cyclin D, E, p16, 21, 27, and Rb. A real-time PCR of the mRNA of cyclin D were completed. RESULTS: In our experiment, B16 cells also dramatically abrogated the G2 checkpoint and were found to arrest in the early G1 phase by treatment with 0.5 μM for 4 hours observed by flow cytometry. Cyclin D mRNA decreased within 4 hours observed by Real-time PCR. Rb was dephosphrylated for 24 hours. However, B16 cells did not undergo cell death after 0.5 μM treatment for 24 hours. Immnofluoscence microscopy showed that the cells become round and small in the morphogenesis. More interesting phenomena were that microtubule stabilization was blocked, and Wee1 distribution was restricted after treatment for 4 hours. CONCLUSION: We analyzed the effect of Wee1 inhibitor PD0166285 described first by Wang in the G2 transition in the B16 melanoma cell line. The inhibitor PD0166285 abrogated G2/M checkpoint inducing early cell division. Moreover, we found that the treatment of cells with the inhibitor is related to microtubule stabilization and decrease in cyclin D transcription. These effects together suggest that Wee1 inhibitor may thus be a potentially useful anti-cancer therapy
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