5,491 research outputs found

    SPHK1 regulates proliferation and survival responses in triplenegative breast cancer

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    Triple-negative breast cancer (TNBC) is characterized by unique aggressive behavior and lack of targeted therapies. Among the various molecular subtypes of breast cancer, it was observed that TNBCs express elevated levels of sphingosine kinase 1 (SPHK1) compared to other breast tumor subtypes. High levels of SPHK1 gene expression correlated with poor overall and progression- free survival, as well as poor response to Doxorubicin-based treatment. Inhibition of SPHK1 was found to attenuate ERK1/2 and AKT signaling and reduce growth of TNBC cells in vitro and in a xenograft SCID mouse model. Moreover, SPHK1 inhibition by siRNA knockdown or treatment with SKI-5C sensitizes TNBCs to chemotherapeutic drugs. Our findings suggest that SPHK1 inhibition, which effectively counteracts oncogenic signaling through ERK1/2 and AKT pathways, is a potentially important anti-tumor strategy in TNBC. A combination of SPHK1 inhibitors with chemotherapeutic agents may be effective against this aggressive subtype of breast cancer

    Syngas Production from Glycerol-dry(CO2) Reforming Over La-promoted Ni/Al2O3 Catalyst

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    A 3 wt% La-promoted Ni/Al2O3 catalyst was prepared via wet co-impregnation technique and physicochemically-characterized. Lanthanum was responsible for better metal dispersion; hence higher BET specific surface area (96.0 m2 g−1) as compared to the unpromoted Ni/Al2O3 catalyst (85.0 m2 g−1). In addition, the La-promoted catalyst possessed finer crystallite size (9.1 nm) whilst the unpromoted catalyst measured 12.8 nm. Subsequently, glycerol dry reforming was performed at atmospheric pressure and temperatures ranging from 923 to 1123 K employing CO2-to-glycerol ratio from zero to five. Significantly, the reaction results have yielded syngas as main gaseous products with H2:CO ratios always below than 2.0 with concomitant maximum 96% glycerol conversion obtained at the CO2-to-glycerol ratio of 1.67. In addition, the glycerol consumption rate can be adequately captured using power law modelling with the order of reactions equal 0.72 and 0.14 with respect to glycerol and CO2 whilst the activation energy was 35.0 kJ mol−1. A 72 h longevity run moreover revealed that the catalyst gave a stable catalytic performance

    Immunofluorescence Assay for Serologic Diagnosis of SARS

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    We evaluated a virus-infected cell-based indirect immunofluorescence assay for detecting anti–severe acute respiratory syndrome-associated coronavirus (SARS-CoV) immunoglobulin (Ig) G antibody. All confirmed SARS cases demonstrated seroconversion or fourfold rise in IgG antibody titer; no control was positive. Sensitivity and specificity of this assay were both 100%. Immunofluorescence assay can ascertain the status of SARS-CoV infection

    EFFECT OF CALCINATION ON THE SINTERING BEHAVIOUR OF HYDROXYAPATITE

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    In this study, a wet chemically produced hydroxyapatite (HA) powder was subjected to calcination at 700, 800, 900 and 1000oC. Subsequently, the sintering behaviour of these calcined powders was studied at various temperatures, ranging from 1050 to 1350oC. XRD results revealed that calcination has no effect on the phase stability of hydroxyapatite. However, the XRD peaks showed that the crystallinity of the powder increased with increasing calcination temperature. The specific surface area of powder reduced drastically from 60.74 m2 ∙g-1 to 9.45 m2 ∙g-1 with increasing calcination temperature. The SEM micrographs of calcined powder showed the coarsening of powder particles as the calcination temperature was increased. In terms of sinterability, the uncalcined HA powder sintered at 1150oC was found to possess the optimum properties with the following values being recorded: ~ 99 % relative density, Vickers hardness of 7.23 GPa and fracture toughness of 1.12 MPa∙m1/2. The present research indicated that calcination of the HA powder prior to sintering has a negligible effect on the sintering behaviour of the HA compacts and that calcination at 1000oC was found to be unfavourable to the properties of sintered HA

    Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces

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    TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of TRIM5α to the assembled capsid is essential for restriction and requires the coiled-coil and B30.2/SPRY domains, but the molecular mechanism of restriction is not fully understood. In this study, we investigated, by cryoEM combined with mutagenesis and chemical cross-linking, the direct interactions between HIV-1 capsid protein (CA) assemblies and purified TRIM5αrh containing coiled-coil and SPRY domains (CC-SPRYrh). Concentration-dependent binding of CC-SPRYrh to CA assemblies was observed, while under equivalent conditions the human protein did not bind. Importantly, CC-SPRYrh, but not its human counterpart, disrupted CA tubes in a non-random fashion, releasing fragments of protofilaments consisting of CA hexamers without dissociation into monomers. Furthermore, such structural destruction was prevented by inter-hexamer crosslinking using P207C/T216C mutant CA with disulfide bonds at the CTD-CTD trimer interface of capsid assemblies, but not by intra-hexamer crosslinking via A14C/E45C at the NTD-NTD interface. The same disruption effect by TRIM5αrh on the inter-hexamer interfaces also occurred with purified intact HIV-1 cores. These results provide insights concerning how TRIM5α disrupts the virion core and demonstrate that structural damage of the viral capsid by TRIM5α is likely one of the important components of the mechanism of TRIM5α-mediated HIV-1 restriction. © 2011 Zhao et al

    Graft-vs-tumor effect in patients with advanced nasopharyngeal cancer treated with nonmyeloablative allogeneic PBSC transplantation

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    While nonmyeloablative peripheral blood stem cell transplantation (NST) has shown efficacy against several solid tumors, it is untested in nasopharyngeal cancer (NPC). In a phase II clinical trial, 21 patients with pretreated metastatic NPC underwent NST with sibling PBSC allografts, using CY conditioning, thymic irradiation and in vivo T-cell depletion with thymoglobulin. Stable lymphohematopoietic chimerism was achieved in most patients and prophylactic CYA was tapered at a median of day +30. Seven patients (33%) showed partial response and three (14%) achieved stable disease. Four patients were alive at 2 years and three showed prolonged disease control of 344, 525 and 550 days. With a median follow-up of 209 (4–1147) days, the median PFS was 100 days (95% confidence interval (CI), 66–128 days), and median OS was 209 days (95% CI, 128–236 days). Patients with chronic GVHD had better survival—median OS 426 days (95% CI, 194–NE days) vs 143 days (95% CI, 114–226 days) (P=0.010). Thus, NST may induce meaningful clinical responses in patients with advanced NPC

    Advances in small lasers

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    M.T.H was supported by an Australian Research council Future Fellowship research grant for this work. M.C.G. is grateful to the Scottish Funding Council (via SUPA) for financial support.Small lasers have dimensions or modes sizes close to or smaller than the wavelength of emitted light. In recent years there has been significant progress towards reducing the size and improving the characteristics of these devices. This work has been led primarily by the innovative use of new materials and cavity designs. This Review summarizes some of the latest developments, particularly in metallic and plasmonic lasers, improvements in small dielectric lasers, and the emerging area of small bio-compatible or bio-derived lasers. We examine the different approaches employed to reduce size and how they result in significant differences in the final device, particularly between metal- and dielectric-cavity lasers. We also present potential applications for the various forms of small lasers, and indicate where further developments are required.PostprintPeer reviewe
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