308 research outputs found

    Applying positive psychology to selling behaviors: A moderated–mediation analysis integrating subjective well-being, coping and organizational identity

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    Subjective well-being (SWB) has been widely found to have a profound impact on the individual, yet its application in the sales field remains unexplored. Applying Broaden and Build theory, this study examines SWB and its influence on the selling behaviors, specifically adaptive selling and sales creativity. Using salesperson coping as a mediator and organizational identity (OI) as a moderator, the relationship between SWB and selling behaviors was further explored. Survey results from 334 sales professionals from multiple industries in India showed that SWB enhances adaptive selling and sales creativity directly and via the mediating effect of salesperson coping. Our results helps us to better understand this potential strategic synergy between salespeople's internal qualities and skills and their organizational identity, our research highlights on what we believe are three key contributors to salesperson creativity and adaptive selling: subjective wellbeing (SWB), positive coping, and organizational identity (OI)

    Sorting Nexin 1 Down-Regulation Promotes Colon Tumorigenesis

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    PURPOSE: Colon cancer is one of the most common human malignancies, yet studies have only begun to identify the multiple mechanisms that underlie the development of this tumor. In this study, we have identified a novel mechanism, dysregulation of endocytic sorting, which promotes colon cancer development. EXPERIMENTAL DESIGN: Immunohistochemical and microarray analyses were done on human colon cancer tissue specimens to determine the levels of one endocytic protein, sorting nexin 1 (SNX1). SW480 cells, a human colon cancer cell line that retains a relatively high level of SNX1 expression, were used to assess the effects of down-regulating this protein by small hairpin RNA. Activation of signal transduction cascades was evaluated in these cells using Western blotting, and multiple functional assays were done. RESULTS: We determined by immunohistochemistry that the level of SNX1 was significantly down-regulated in 75% of human colon cancers. In corroborative studies using microarray analysis, SNX1 message was significantly decreased (log(2) ratio less than -1) for 8 of 19 colon carcinomas. Cell lines with reduced SNX1 levels showed increased proliferation, decreased apoptosis, and decreased susceptibility to anoikis. They also showed increased activation of epidermal growth factor receptor and extracellular signal-regulated kinase 1/2 in response to epidermal growth factor. This increased activation was abolished by inhibition of endocytosis. CONCLUSIONS: These data suggest that loss of SNX1 may play a significant role in the development and aggressiveness of human colon cancer, at least partially through the mechanism of increased signaling from endosomes. Further, these findings suggest that dysregulation of endocytic proteins may represent a new paradigm in the process of carcinogenesis.Fil: Nguyen, Lananh N.. University of Washington; Estados UnidosFil: Holdren, Matthew S.. University of Washington; Estados UnidosFil: Nguyen, Anthony P.. Baylor College of Medicine; Estados UnidosFil: Furuya, Momoko H.. University of Washington; Estados UnidosFil: Bianchini, Michele. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Levy, Estrella Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Mordoh, Jose. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Liu, Annie. University of Washington; Estados UnidosFil: Guncay, Gabriela D.. University of Washington; Estados UnidosFil: Campbell, Jean S.. University of Washington; Estados UnidosFil: Parks, W. Tony. University of Washington; Estados Unido

    The Caltech CSN project collects sensor data from thousands of personal devices for realtime response to dangerous earthquakes

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    The proliferation of smartphones and other powerful sensor-equipped consumer devices enables a new class of Web application: community sense and response (CSR) systems, distinguished from standard Web applications by their use of community-owned commercial sensor hardware. Just as social networks connect and share human-generated content, CSR systems gather, share, and act on sensory data from users' Internet-enabled devices. Here, we discuss the Caltech Community Seismic Network (CSN) as a prototypical CSR system harnessing accelerometers in smartphones and consumer electronics, including the systems and algorithmic challenges of designing, building, and evaluating a scalable network for real-time awareness of dangerous earthquakes

    Engineering Plateau Phase Transition in Quantum Anomalous Hall Multilayers

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    The plateau phase transition in quantum anomalous Hall (QAH) insulators corresponds to a quantum state wherein a single magnetic domain gives way to multiple magnetic domains and then re-converges back to a single magnetic domain. The layer structure of the sample provides an external knob for adjusting the Chern number C of the QAH insulators. Here, we employ molecular beam epitaxy (MBE) to grow magnetic topological insulator (TI) multilayers with an asymmetric layer structure and realize the magnetic field-driven plateau phase transition between two QAH states with odd Chern number change {\Delta}C. In multilayer structures with C=+-1 and C=+-2 QAH states, we find two characteristic power-law behaviors between temperature and the scaling variables on the magnetic field at transition points. The critical exponents extracted for the plateau phase transitions with {\Delta}C=1 and {\Delta}C=3 in QAH insulators are found to be nearly identical, specifically, k1~0.390+-0.021 and k2~0.388+-0.015, respectively. We construct a four-layer Chalker-Coddington network model to understand the consistent critical exponents for the plateau phase transitions with {\Delta}C=1 and {\Delta}C=3. This work will motivate further investigations into the critical behaviors of plateau phase transitions with different {\Delta}C in QAH insulators and provide new opportunities for the development of QAH chiral edge current-based electronic and spintronic devices.Comment: 18 pages, 4 figures. Comments are welcom

    Telomerase and Telomere Length in Pulmonary Fibrosis

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    In addition to its expression in stem cells and many cancers,telomerase activity is transiently induced inmurine bleomycin (BLM)induced pulmonary fibrosis with increased levels of telomerase transcriptase (TERT) expression, which is essential for fibrosis. To extend these observations to human chronic fibrotic lung disease,we investigated the expression of telomerase activity in lung fibroblasts from patients with interstitial lung diseases (ILDs), including idiopathic pulmonaryfibrosis (IPF).The resultsshowedthat telomerase activity was induced in more than 66% of IPF lung fibroblast samples, in comparison with less than 29% from control samples,some of which were obtained from lung cancer resections. Less than 4%of the humanIPF lung fibroblast samples exhibited shortened telomeres,whereas less than 6% of peripheral blood leukocyte samples from patients with IPF or hypersensitivity pneumonitis demonstrated shortened telomeres. Moreover, shortened telomeres in lategeneration telomerase RNA component knockout mice did not exert a significant effect on BLM-induced pulmonary fibrosis. In contrast, TERT knockout mice exhibited deficient fibrosis that was independent of telomere length. Finally, TERT expression was up-regulated by a histone deacetylase inhibitor, while the induction of TERT in lung fibroblastswasassociatedwiththebindingofacetylatedhistoneH3K9to the TERT promoter region. These findings indicate that significant telomerase inductionwas evident in fibroblasts from fibroticmurine lungs and a majority of IPF lung samples, whereas telomere shortening was not a common finding in the human blood and lung fibroblast samples. Notably, the animal studies indicated that the pathogenesis of pulmonary fibrosis was independent of telomere length

    Analytical and biological variability in biomarker measurement in the Hispanic Community Health Study/Study of Latinos

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    Biomarker variability, which includes within-individual variability (CVI), between-individual variability (CVG) and methodological variability (CVP+A) is an important determinant of our ability to detect biomarker-disease associations. Estimates of CVI and CVG may be population specific and little data exists on biomarker variability in diverse Hispanic populations. Hence, we evaluated all 3 components of biomarker variability in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) using repeat blood collections (n=58) and duplicate blood measurements (n = 761 – 929 depending on the biomarker)

    Staphylococcus aureus α-toxin impairs early neutrophil localization via electrogenic disruption of store-operated calcium entry

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    The pore-forming S. aureus α-toxin (Hla) contributes to virulence and disease pathogenesis. While high concentrations of toxin induce cell death, neutrophils exhibit relative resistance to lysis, suggesting that the action of Hla may not be solely conferred by lytic susceptibility. Using intravital microscopy, we observed that Hla disrupts neutrophil localization and clustering early in infection. Hla forms a narrow, ion-selective pore, suggesting that Hla may dysregulate calcium or other ions to impair neutrophil function. We found that sub-lytic Hla did not permit calcium influx but caused rapid membrane depolarization. Depolarization decreases the electrogenic driving force for calcium, and concordantly, Hla suppressed calcium signaling in vitro and in vivo and calcium-dependent leukotriene B4 (LTB4) production, a key mediator of neutrophil clustering. Thus, Hla disrupts the early patterning of the neutrophil response to infection, in part through direct impairment of neutrophil calcium signaling. This early mis-localization of neutrophils may contribute to establishment of infection

    Proactive vaccination using multiviral Quartet Nanocages to elicit broad anti-coronavirus responses

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    Defending against future pandemics requires vaccine platforms that protect across a range of related pathogens. Nanoscale patterning can be used to address this issue. Here, we produce quartets of linked receptor-binding domains (RBDs) from a panel of SARS-like betacoronaviruses, coupled to a computationally designed nanocage through SpyTag/SpyCatcher links. These Quartet Nanocages, possessing a branched morphology, induce a high level of neutralizing antibodies against several different coronaviruses, including against viruses not represented in the vaccine. Equivalent antibody responses are raised to RBDs close to the nanocage or at the tips of the nanoparticle’s branches. In animals primed with SARS-CoV-2 Spike, boost immunizations with Quartet Nanocages increase the strength and breadth of an otherwise narrow immune response. A Quartet Nanocage including the Omicron XBB.1.5 ‘Kraken’ RBD induced antibodies with binding to a broad range of sarbecoviruses, as well as neutralizing activity against this variant of concern. Quartet nanocages are a nanomedicine approach with potential to confer heterotypic protection against emergent zoonotic pathogens and facilitate proactive pandemic protection

    An image analysis toolbox for high-throughput C. elegans assays

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    We present a toolbox for high-throughput screening of image-based Caenorhabditis elegans phenotypes. The image analysis algorithms measure morphological phenotypes in individual worms and are effective for a variety of assays and imaging systems. This WormToolbox is available through the open-source CellProfiler project and enables objective scoring of whole-worm high-throughput image-based assays of C. elegans for the study of diverse biological pathways that are relevant to human disease.National Institutes of Health (U.S.) (U54 EB005149

    Identification of QTL genes for BMD variation using both linkage and gene-based association approaches

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    Low bone mineral density (BMD) is a risk factor for osteoporotic fracture with a high heritability. Previous large scale linkage study in Northern Chinese has identified four significant quantitative trait loci (QTL) for BMD variation on chromosome 2q24, 5q21, 7p21 and 13q21. We performed a replication study of these four QTL in 1,459 Southern Chinese from 306 pedigrees. Successful replication was observed on chromosome 5q21 for femoral neck BMD with a LOD score of 1.38 (nominal p value = 0.006). We have previously identified this locus in a genome scan meta-analysis of BMD variation in a white population. Subsequent QTL-wide gene-based association analysis in 800 subjects with extreme BMD identified CAST and ERAP1 as novel BMD candidate genes (empirical p value of 0.032 and 0.014, respectively). The associations were independently replicated in a Northern European population (empirical p value of 0.01 and 0.004 for CAST and ERAP1, respectively). These findings provide further evidence that 5q21 is a BMD QTL, and CAST and ERAP1 may be associated with femoral neck BMD variation
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