883 research outputs found

    Satisfaction With Businesses?

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    We examine how power distance belief (PDB) -the prevalence of inequality in society -affects consumers' satisfaction with loyalty programs. Five studies support the counterintuitive hypothesis that high (vs. low) PDB contexts decrease, rather than increase, nonloyalty-status consumers' satisfaction with such businesses, and illuminate the underlying mechanisms

    Methoxy-phenyl groups reduce the cytotoxicity and increase the aqueous solubility of phosphonium zwitterions and salts

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    The ability of phosphonium cations to act as intracellular transport vectors is well-established. Previous research has demonstrated that phosphonioalkylthiosulfate zwitterions, and -thioacetylalkylphosphonium salts are useful precursors for the formation of phosphonium-functionalised gold nanoparticles and enable the nanoparticles to be transported into cells for diagnostic and therapeutic purposes. In this report we describe the synthesis and characterisation of a series of phosphonioalkylthiosulfate zwitterions, and-thioacetylalkylphosphonium salts derived from the methoxy-phenylphosphines tris(2,4,6-trimethoxyphenyl)phosphine, tris(2,6-dimethoxyphenyl)phosphine and tri(4-methoxyphenyl)phosphine. The methoxyphenyl-substituted phosphonium compounds show greater solubility in aqueous systems than the corresponding phenyl derivatives and cytotoxicity studies reveal that the compounds are significantly less toxic than the related triphenylphosphonium derivatives. The solid-state structures of the tris(2,4,6-trimethoxyphenyl)- and tris(2,6-dimethoxyphenyl)-phosphoniopropylthiosulfate zwitterions have been investigated by single crystal X-ray crystallography. The differences in the molecular packing of the compounds may account for greater solubility of these zwitterions in aqueous solutions

    Replication in the Mononuclear Phagocyte System (MPS) as a Determinant of Hantavirus Pathogenicity

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    Members of different virus families including Hantaviridae cause viral hemorrhagic fevers (VHFs). The decisive determinants of hantavirus-associated pathogenicity are still enigmatic. Pathogenic hantavirus species, such as Puumala virus (PUUV), Hantaan virus (HTNV), Dobrava-Belgrade virus (DOBV), and Sin Nombre virus (SNV), are associated with significant case fatality rates. In contrast, Tula virus (TULV) only sporadically causes mild disease in immunocompetent humans and Prospect Hill virus (PHV) so far has not been associated with any symptoms. They are thus defined here as low pathogenic/apathogenic hantavirus species. We found that productive infection of cells of the mononuclear phagocyte system (MPS), such as monocytes and dendritic cells (DCs), correlated well with the pathogenicity of hantavirus species tested. HTNV (intermediate case fatality rates) replicated more efficiently than PUUV (low case fatality rates) in myeloid cells, whereas low pathogenic/apathogenic hantavirus species did not produce any detectable virus titers. Analysis of PHPUV, a reassortant hantavirus derived from a pathogenic (PUUV) and an apathogenic (PHV) hantavirus species, indicated that the viral glycoproteins are not decisive for replication in MPS cells. Moreover, blocking acidification of endosomes with chloroquine decreased the number of TULV genomes in myeloid cells suggesting a post-entry block for low pathogenic/apathogenic hantavirus species in myeloid cells. Intriguingly, pathogenic but not low pathogenic/apathogenic hantavirus species induced conversion of monocytes into inflammatory DCs. The proinflammatory programming of MPS cells by pathogenic hantavirus species required integrin signaling and viral replication. Our findings indicate that the capacity to replicate in MPS cells is a prominent feature of hantaviral pathogenicity

    Triphenylarsonium-functionalised gold nanoparticles: potential nanocarriers for intracellular therapeutics.

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    This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.Two new triphenylarsonium alkylthiolate precursors, a thiosulfate zwitterion and a thioacetate salt, have been structurally characterised and their cytotoxicity evaluated against PC3 cells. The arsonium compounds have been used to prepare gold nanoparticles decorated with triphenylarsonium groups.Sheffield Hallam University and Indian Institute of Science (NL)

    Axitinib inhibits retinal and choroidal neovascularization in in vitro and in vivo models

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    AbstractAge-related Macular Degeneration (AMD) is the leading cause of visual impairment and blindness in the elderly in developed countries. Neovascular/exudative (wet) AMD is the aggressive form of AMD and can involve choroidal neovascularization and vascular leakage. Anti-vascular endothelial growth factor (anti-VEGF) medications have significantly improved treatment of wet-AMD. However, only approximately 40% of patients obtain full benefit from anti-VEGF therapy and the medications are given by intravitreal injection. Axitinib, a small molecule multi-receptor tyrosine kinase inhibitor used for the treatment of advanced renal cell carcinoma, is taken orally and inhibits VEGF activity by blocking VEGF receptors. Axitinib also has the advantage of blocking platelet derived growth factor (PDGF) receptors which play a role in neovascularization. Using in vitro human retinal microvascular endothelial cells (HRMVECs), human brain vascular pericytes (HBVRs), 3D co-culture vessel sprout assay, and in vivo laser induced rat choroidal neovascularization (CNV) models, the effect of axitinib on neovascularization was evaluated. Axitinib inhibited neovascularization better than anti-VEGF and/or anti-hPDGF-B mAb in the in vitro models demonstrating that combined inhibition of both VEGF and PDGF pathways may be synergistic in treating wet-AMD. Additionally, axitinib showed good efficacy at a low dose (0.875 mg/day) in laser-induced CNV model in rats. In conclusion our data shows that axitinib, an inhibitor of VEGF and PDGF-B pathways may be useful in ameliorating wet-AMD therapy

    Tissue-specific calibration of extracellular matrix material properties by transforming growth factor-beta and Runx2 in bone is required for hearing

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    Publisher version: http://www.nature.com/embor/journal/v11/n10/full/embor2010135.htmlDA - 20100917 IS - 1469-3178 (Electronic) IS - 1469-221X (Linking) LA - ENG PT - JOURNAL ARTICLEDA - 20100917 IS - 1469-3178 (Electronic) IS - 1469-221X (Linking) LA - ENG PT - JOURNAL ARTICLEDA - 20100917 IS - 1469-3178 (Electronic) IS - 1469-221X (Linking) LA - ENG PT - JOURNAL ARTICLEPhysical cues, such as extracellular matrix stiffness, direct cell differentiation and support tissue-specific function. Perturbation of these cues underlies diverse pathologies, including osteoarthritis, cardiovascular disease and cancer. However, the molecular mechanisms that establish tissue-specific material properties and link them to healthy tissue function are unknown. We show that Runx2, a key lineage-specific transcription factor, regulates the material properties of bone matrix through the same transforming growth factor-beta (TGFbeta)-responsive pathway that controls osteoblast differentiation. Deregulated TGFbeta or Runx2 function compromises the distinctly hard cochlear bone matrix and causes hearing loss, as seen in human cleidocranial dysplasia. In Runx2(+/-) mice, inhibition of TGFbeta signalling rescues both the material properties of the defective matrix, and hearing. This study elucidates the unknown cause of hearing loss in cleidocranial dysplasia, and demonstrates that a molecular pathway controlling cell differentiation also defines material properties of extracellular matrix. Furthermore, our results suggest that the careful regulation of these properties is essential for healthy tissue functio

    Monocyte apoptosis in patients with active lupus

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    No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37808/1/1780390827_ftp.pd

    A prospective study of hearing changes after beginning zidovudine or didanosine in HIV-1 treatment-naĂŻve people

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    BACKGROUND: While hearing loss in HIV-infected people after beginning nucleoside reverse transcriptase inhibitors (NRTIs) has been reported, there have been no prospective studies that measured hearing changes longitudinally in treatment-naĂŻve HIV-infected subjects following initiation of regimens containing NRTIs. The goal of this study was to conduct a prospective assessment of the contribution of zidovudine (ZDV) and didanosine (ddI) to hearing loss METHODS/DESIGN: A prospective observational pilot study to determine whether ZDV or ddI, alone or in combination, are associated with sensorineural hearing loss in HIV-infected persons. Changes in hearing levels at all frequencies and in low and high frequency pure tone averages were measured at baseline, 16, and 32 weeks after initiating antiretroviral therapy. DISCUSSION: Treatment with ZDV and ddI did not result in loss of hearing, even after taking into account noise exposure, immune status and age. The results of this prospective pilot study do not support the notion that treatment with nucleoside antiretrovirals damages hearing
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