67 research outputs found

    Time-Periodic Solutions of the Einstein's Field Equations II

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    In this paper, we construct several kinds of new time-periodic solutions of the vacuum Einstein's field equations whose Riemann curvature tensors vanish, keep finite or take the infinity at some points in these space-times, respectively. The singularities of these new time-periodic solutions are investigated and some new physical phenomena are found. The applications of these solutions in modern cosmology and general relativity can be expected.Comment: 10 pages, 1 figur

    Phosphorylated ERK is a potential predictor of sensitivity to sorafenib when treating hepatocellular carcinoma: evidence from an in vitro study

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    <p>Abstract</p> <p>Background</p> <p>Sorafenib is the first agent that has demonstrated an improved overall survival benefit in advanced hepatocellular carcinoma (HCC), setting a new standard for first-line treatment. However, no one has yet been able to predict sensitivity to sorafenib. Pre-treatment pERK level has been shown to be associated with favorable response to such therapy in a phase II clinical study, indicating that pERK may be a potential biomarker for treatment of HCC with sorafenib.</p> <p>Methods</p> <p>The effects of sorafenib and 5-fluorouracil (5-FU) on cell proliferation were evaluated by cell viability assays in four HCC cell lines (SMMC-7721, MHCC97-L, MHCC97-H and HCCLM6) with different metastatic potential and basal pERK expression levels. Expression levels of pERK were determined by immunocytochemical quantification together with western blot analysis, and pERK density values were also calculated. Correlation analyses were then carried out between the IC<sub>50 </sub>values of drugs and pERK density values. After basal ERK phosphorylation was down-regulated with U0126 in MHCC97-H cells, cellular responsiveness to sorafenib was assessed by cell viability assay.</p> <p>Results</p> <p>Basal pERK levels increased stepwise in cell lines in accordance with their metastatic potential. Sorafenib inhibited ERK phosphorylation in a dose-dependent manner in all four cell lines at a concentration between 5 and 20 μM, but the degree of inhibition was significantly different according to their basal pERK expression level (<it>P </it>< 0.0001). In contrast, no significant change was observed after 5-FU treatment. Correlation analyses between the IC<sub>50 </sub>values and pERK densities revealed that the effects of sorafenib on cell proliferation were significantly correlated with basal pERK levels (Spearman r = -0.8671, <it>P </it>= 0.0003). Resistance to 5-FU was also significantly associated with basal pERK expression in these HCC cell lines (Spearman r = 0.7832, <it>P </it>= 0.0026). After the basal ERK phosphorylation level in MHCC97-H cells was reduced with U0126, they were significantly less sensitive to sorafenib-mediated growth inhibition, with an IC<sub>50 </sub>of 17.31 ± 1.62 μM versus 10.81 ± 1.24 μM (<it>P </it>= 0.0281).</p> <p>Conclusion</p> <p>In this <it>in vitro </it>study, pERK was confirmed to be a potential biomarker predictive of sensitivity to sorafenib in treating HCC. The RAF/MEK/ERK pathway may be involved in drug resistance to traditional chemotherapy in HCC.</p

    The Kuroshio Extension : a leading mechanism for the seasonal sea-level variability along the west coast of Japan

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    Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Ocean Dynamics 60 (2010): 667-672, doi:10.1007/s10236-009-0239-9.Sea level changes coherently along the two coasts of Japan on the seasonal time scale. AVISO satellite altimetry data and OFES (OGCM for the Earth Simulator) results indicate that the variation propagates clockwise from Japan's east coast through the Tsushima Strait into the Japan/East Sea (JES) and then northward along the west coast. In this study, we hypothesize and test numerically that the sea level variability along the west coast of Japan is remotely forced by the Kuroshio Extension (KE) off the east coast. Topographic Rossby waves and boundary Kelvin waves facilitate the connection. Our 3-d POM model when forced by observed wind stress reproduces well the seasonal changes in the vicinity of JES. Two additional experiments were conducted to examine the relative roles of remote forcing and local forcing. The sea level variability inside the JES was dramatically reduced when the Tsushima Strait is blocked in one experiment. The removal of the local forcing, in another experiment, has little effect on the JES variability. Both experiments support our hypothesis that the open-ocean forcing, possibly through the KE variability, is the leading forcing mechanism for sea level change along the west coast of Japan.This work was conducted when Chao Ma was a visiting graduate student at WHOI. His visit has been supported by China Scholarship Council and WHOI Academics Office. This study has been supported by WHOI’s Coastal Ocean Institute, the National Basic Research Program of China 2005CB422303 and 2007CB481804), the International Science and Technology Cooperation Program of China (2006DFB21250), the Natural Science Foundation of China (40706006) , and the Ministry of Education’s 111 Project (B07036). Lin was supported by the Program for New Century Excellent Talents in University (NECT-07-0781)

    First-Principles Study of the Band Gap Structure of Oxygen-Passivated Silicon Nanonets

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    A net-like nanostructure of silicon named silicon nanonet was designed and oxygen atoms were used to passivate the dangling bonds. First-principles calculation based on density functional theory with the generalized gradient approximation (GGA) were carried out to investigate the energy band gap structure of this special structure. The calculation results show that the indirect–direct band gap transition occurs when the nanonets are properly designed. This band gap transition is dominated by the passivation bonds, porosities as well as pore array distributions. It is also proved that Si–O–Si is an effective passivation bond which can change the band gap structure of the nanonets. These results provide another way to achieve a practical silicon-based light source

    An analysis of farmers' perception of the new cooperative medical system in Liaoning Province, China

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    <p>Abstract</p> <p>Background</p> <p>Since 2003, the number of pilot areas of the New Rural Cooperative Medical System (NRCMS) has increased in rural China. And the major efforts have been concentrated on the enrollment of prospective members. In this study, we examined the satisfaction of the rural residents with the NRCMS as well as factors affecting their attitudes towards the NRCMS.</p> <p>Methods</p> <p>The data for this study were collected from a survey involving twenty counties in Liaoning Province. Interviews and focus groups were conducted between 10<sup>th </sup>January and 20<sup>th </sup>August 2008. A total of 2,780 people aged 18-72 were randomly selected and interviewed. Data were evaluated by nonparametric tests and ordinal regression models.</p> <p>Results</p> <p>71.6% of the study subjects were satisfied with the NRCMS. Single factor analysis showed that attitudes towards the NRCMS were influenced by gender, age, marital status, and self-rated health status. In the ordinal regression analysis, gender, age, and self-rated health status affect satisfaction (P < 0.05).</p> <p>Conclusions</p> <p>We found that a considerable proportion of farmers were satisfied with the NRCMS. Gender, age, and self-rated health status had significant effects on farmers' attitudes towards the NRCMS. The Chinese Central Government attempted to adopt active measures in the future to continuously improve the NRCMS, including initiating educational programs, building new medical facilities and increasing financial investment.</p

    Prevalence of primary biliary cirrhosis in adults referring hospital for annual health check-up in Southern China

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    <p>Abstract</p> <p>Background</p> <p>Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the presence of anti-mitocondrial autoantibodies (AMA) which has an essential role also for diagnosis. In addition, also some anti-nuclear antibodies (ANA) have been shown to be highly specific PBC. The purpose of this study was to assess the prevalence of PBC among the adults referring hospital for annual health check-up in Southern China by screening sera for PBC-specific autoantibodies.</p> <p>Methods</p> <p>AMA and ANA were screened in 8,126 adults (mean age 44 ± 15 years, 48% females) by indirect immunofluorenscence (IIF). Positive sera were tested by ELISA/immunoblotting for AMA-M2, anti-sp100 and anti-gp210. A diagnosis of PBC was re-assessed six months after the initial testing.</p> <p>Results</p> <p>Out of 8,126 individuals 35 were positive for AMA and 79 positive for ANA. Nineteen, 4, and 3 of the subjects positive for AMA and/or ANA showed reactivity for AMA-M2, anti-sp100 or gp210, respectively, further tested with ELISA/immunoblotting. Fourteen in the 39 individuals positive for AMA at IIF, AMA-M2, anti-gp210, or anti-sp100 had abnormal cholestatic liver functional indices. One definite and 3 probable PBC diagnosis could be made in 4 cases including 3 females and 1 male after half a year.</p> <p>Conclusions</p> <p>We found a point prevalence rate of PBC among Southern Chinese adults attending for yearly health check-up of 492 cases per million (95% CI, 128 to 1,093) and 1,558 cases per million (95% CI, 294 to 3,815) for women over 40, a finding similar to prevalence reported in other geographical areas.</p

    GPVI and GPIbα Mediate Staphylococcal Superantigen-Like Protein 5 (SSL5) Induced Platelet Activation and Direct toward Glycans as Potential Inhibitors

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    Background Staphylococcus aureus (S. aureus) is a common pathogen capable of causing life-threatening infections. Staphylococcal superantigen-like protein 5 (SSL5) has recently been shown to bind to platelet glycoproteins and induce platelet activation. This study investigates further the interaction between SSL5 and platelet glycoproteins. Moreover, using a glycan discovery approach, we aim to identify potential glycans to therapeutically target this interaction and prevent SSL5-induced effects. Methodology/Principal Findings In addition to platelet activation experiments, flow cytometry, immunoprecipitation, surface plasmon resonance and a glycan binding array, were used to identify specific SSL5 binding regions and mediators. We independently confirm SSL5 to interact with platelets via GPIbα and identify the sulphated-tyrosine residues as an important region for SSL5 binding. We also identify the novel direct interaction between SSL5 and the platelet collagen receptor GPVI. Together, these receptors offer one mechanistic explanation for the unique functional influences SSL5 exerts on platelets. A role for specific families of platelet glycans in mediating SSL5-platelet interactions was also discovered and used to identify and demonstrate effectiveness of potential glycan based inhibitors in vitro. Conclusions/Significance These findings further elucidate the functional interactions between SSL5 and platelets, including the novel finding of a role for the GPVI receptor. We demonstrate efficacy of possible glycan-based approaches to inhibit the SSL5-induced platelet activation. Our data warrant further work to prove SSL5-platelet effects in viv

    Cu-64-Labeled Phosphonate Cross-Bridged Chelator Conjugates of c(RGDyK) for PET/CT Imaging of Osteolytic Bone Metastases

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    Objective: The goal of this research was to evaluate c(RGDyK) conjugated to phosphonate-based cross-bridged chelators using Cu-free click chemistry in the 4T1 mouse mammary tumor bone metastasis model in comparison with Cu-64-CB-TE2A-c(RGDyK), which previously showed selective binding to integrin v3 on osteoclasts. Experimental: Two phosphonate-based cross-bridged chelators (CB-TE1A1P and CB-TE1K1P) were conjugated to c(RGDyK) through bio-orthogonal strain-promoted alkyne-azide cycloaddition. In vitro and in vivo evaluation of the Cu-64-labeled TE1A1P-DBCO-c(RGDyK) (AP-c(RGDyK)), TE1K1P-PEG4-DBCO-c(RGDyK) (KP-c(RGDyK)), and CB-TE2A-c(RGDyK) were compared in the 4T1 mouse model of bone metastasis. The affinities of the unconjugated and chelator-c(RGDyK) analogs for v3 integrin were determined using a competitive-binding assay. For in vivo evaluation, BALB/c mice were injected with 1x10(5) 4T1/Luc cells in the left ventricle. Formation of metastases was monitored by bioluminescence imaging (BLI) followed by small-animal PET/CT 2 h postinjection of radiotracers. Results: The chelator-peptide conjugates showed similar affinity to integrin v3, in the low nM range. PET imaging demonstrated a higher uptake in bones having metastases for all Cu-64-labeled c(RGDyK) analogs compared with bones in nontumor-bearing mice. The correlation between uptake of Cu-64-AP-c(RGDyK) and Cu-64-KP-c(RGDyK) in bones with metastases based on PET/CT imaging, and osteoclast number based on histomorphometry, was improved over the previously investigated Cu-64-CB-TE2A-c(RGDyK). Conclusion: These data suggest that the phosphonate chelator conjugates of c(RDGyK) peptides are promising PET tracers suitable for imaging tumor-associated osteoclasts in bone metastases
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