Glycogen synthase kinase 3 beta (GSK3β) is highly inactivated in epithelial cancers and is known to inhibit tumor migration and invasion. The zinc-finger-containing transcriptional repressor, Slug, ...represses E-cadherin transcription and enhances epithelial-mesenchymal transition (EMT). In this study, we find that the GSK3β-pSer9 level is associated with the expression of Slug in non-small cell lung cancer. GSK3β-mediated phosphorylation of Slug facilitates Slug protein turnover. Proteomic analysis reveals that the carboxyl terminus of Hsc70-interacting protein (CHIP) interacts with wild-type Slug (wtSlug). Knockdown of CHIP stabilizes the wtSlug protein and reduces Slug ubiquitylation and degradation. In contrast, nonphosphorylatable Slug-4SA is not degraded by CHIP. The accumulation of nondegradable Slug may further lead to the repression of E-cadherin expression and promote cancer cell migration, invasion and metastasis. Our findings provide evidence of a de novo GSK3β-CHIP-Slug pathway that may be involved in the progression of metastasis in lung cancer.
The unified theory of acceptance and use of technology (UTAUT) is a little over a decade old and has been used extensively in information systems (IS) and other fields, as the large number of ...citations to the original paper that introduced the theory evidences. In this paper, we review and synthesize the IS literature on UTAUT from September 2003 until December 2014, perform a theoretical analysis of UTAUT and its extensions, and chart an agenda for research going forward. Based on Weber's (2012) framework of theory evaluation, we examined UTAUT and its extensions along two sets of quality dimensions; namely, the parts of a theory and the theory as a whole. While our review identifies many merits to UTAUT, we also found that the progress related to this theory has hampered further theoretical development in research into technology acceptance and use. To chart an agenda for research that will enable significant future work, we analyze the theoretical contributions of UTAUT using Whetten's (2009) notion of cross-context theorizing. Our analysis reveals several limitations that lead us to propose a multi-level framework that can serve as the theoretical foundation for future research. Specifically, this framework integrates the notion of research context and cross-context theorizing with the theory evaluation framework to: 1) synthesize the existing UTAUT extensions across both the dimensions and the levels of the research context and 2) highlight promising research directions. We conclude with recommendations for future UTAUT-related research using the proposed framework.
Complex topological configurations are fertile ground for exploring emergent phenomena and exotic phases in condensed-matter physics. For example, the recent discovery of polarization vortices and ...their associated complex-phase coexistence and response under applied electric fields in superlattices of (PbTiO
)
/(SrTiO
)
suggests the presence of a complex, multi-dimensional system capable of interesting physical responses, such as chirality, negative capacitance and large piezo-electric responses
. Here, by varying epitaxial constraints, we discover room-temperature polar-skyrmion bubbles in a lead titanate layer confined by strontium titanate layers, which are imaged by atomic-resolution scanning transmission electron microscopy. Phase-field modelling and second-principles calculations reveal that the polar-skyrmion bubbles have a skyrmion number of +1, and resonant soft-X-ray diffraction experiments show circular dichroism, confirming chirality. Such nanometre-scale polar-skyrmion bubbles are the electric analogues of magnetic skyrmions, and could contribute to the advancement of ferroelectrics towards functionalities incorporating emergent chirality and electrically controllable negative capacitance.
This paper investigates the drivers and inhibitors of Internet privacy concern. Applying the Multidimensional Development Theory to the online environment, we identify the important factors under ...four dimensions—i.e., environmental, individual, information management, and interaction management. We tested our model using data from an online survey of 2417 individuals in Hong Kong. The results show that the factors under all four dimensions are significant in the formation of Internet privacy concern. Specifically, familiarity with government legislation, Internet knowledge, benefit of information disclosure, privacy protection, and social presence reduce Internet privacy concern, while individuals’ previous privacy invasion experience, risk avoidance personality, and sensitivity of information requested by websites increase Internet privacy concern. We conducted an analysis of unobserved heterogeneity to confirm the significance of these factors. A follow-up moderation analysis shows that the individual factors (i.e., previous privacy invasion experience, risk avoidance personality, and Internet knowledge) moderate the effects of the information management factor (i.e., information sensitivity) and the interaction management factors (i.e., privacy protection and social presence). The findings provide an integrated understanding of the formation of Internet privacy concern.
A nasopharyngeal carcinoma (NPC) mass screening trial using a combination of immunoglobulin A antibodies to Epstein-Barr virus capsid antigen and nuclear antigen-1 by enzyme-linked immunosorbent ...assay in addition to indirect mirror examination in the nasopharynx and/or lymphatic palpation (IMLP) was conducted in southern China. Cantonese aged 30-59 years residing in 2 cities randomly selected by cluster sampling, Sihui and Zhongshan, were invited to participate in this screening from May 2008 through May 2010. Participants were offered fiberoptic endoscopy examination and/or pathologic biopsy if their serologic tests reached our predefined level of high risk or if results from the physical examination indicated possible cancer (i.e., were IMLP positive). A total of 28,688 individuals were voluntarily screened in the initial round. The overall NPC detection rate was 0.14% (41/28,688) with an early diagnosis rate of 68.3% (28/41) during the first year of follow-up. Thirty-eight of 41 cases (92.7%) were detected among the high-risk group, and 7 of 41 cases (17.1%) were detected among the IMLP-positive group. The 2 Epstein-Barr virus serologic tests by enzyme-linked immunosorbent assay could be a feasible alternative for NPC screening in endemic areas. Further follow-up is needed to examine whether screening has an effect on decreasing mortality from NPC in these areas.
Internet privacy concerns (IPC) is an area of study that is receiving increased attention due to the huge amount of personal information being gathered, stored, transmitted, and published on the ...Internet. While there is an emerging literature on IPC, there is limited agreement about its conceptualization in terms of its key dimensions and its factor structure. Based on the multidimensional developmental theory and a review of the prior literature, we identify alternative conceptualizations of IPC. We examine the various conceptualizations of IPC with four online surveys involving nearly 4,000 Internet users. As a baseline, study 1 compares the integrated conceptualization of IPC to two existing conceptualizations in the literature. While the results provide support for the integrated conceptualization, the second-order factor model does not outperform the correlated first-order factor model. Study 2 replicates the study on a different sample and confirms the results of study 1. We also investigate whether the prior results are affected by the different perspectives adopted in the wording of items in the original instruments. In study 3, we find that focusing on one's concern for website behavior (rather than one's expectation of website behavior) and adopting a consistent perspective in the wording of the items help to improve the validity of the factor structure. We then examine the hypothesized third-order conceptualizations of IPC through a number of alternative higher-order models. The empirical results confirm that, in general, the third-order conceptualizations of IPC outperform their lower-order alternatives. In addition, the conceptualization of IPC that has the best fit with the data contains a third-order general IPC factor, two second-order factors of interaction management and information management, and six first-order factors (i.e., collection, secondary usage, errors, improper access, control, and awareness). Study 4 cross-validates the results with another data set and examines IPC within the context of a nomological network. The results confirm that the third-order conceptualization of IPC has nomological validity, and it is a significant determinant of both trusting beliefs and risk beliefs. Our research helps to resolve inconsistencies in the key underlying dimensions of IPC, the factor structure of IPC, and the wording of the original items in prior instruments of IPC. Finally, we discuss the implications of this research.
Abstract Background Programmed death-ligand 1 (PD-L1) expression has been suggested as a potential predictive biomarker of response to anti-PD-1/PD-L1 therapy. In this study, we investigated whether ...the expression of PD-L1 in tumour cells is affected by neoadjuvant concurrent chemoradiotherapy (CCRT) or chemotherapy in oesophageal squamous cell carcinoma. Patients and methods Between 2004 and 2014, we collected the medical records of locally advanced oesophageal cancer patients consecutively diagnosed and treated with neoadjuvant CCRT or chemotherapy, followed by curative resection. PD-L1 expression in acquired tissue specimens was evaluated by immunohistochemistry using the H-score. The changes in PD-L1 expression between paired samples were evaluated and we also analysed PD-L1 expression in surgical tumour specimens to evaluate its prognostic role. Results Twenty-eight paired tumour tissues that were acquired before and after neoadjuvant therapy were available: 19 patients with CCRT and 9 with chemotherapy before complete oesophagectomy. The PD-L1 H-score increased significantly from baseline tumour tissues to surgical tumour tissues after neoadjuvant CCRT ( P = 0.007, median H-score from 28 to 52), whereas it decreased significantly after neoadjuvant chemotherapy ( P = 0.048, median H-score from 53 to 22). In a total of 73 patients, including 45 additional cases for the prognosis analysis, patients with higher PD-L1 H-scores (≥20) had poorer overall survival (median 16.7 versus 32.9 months, P = 0.02) than those with lower H-scores (<20). Conclusions PD-L1 expression in tumour cells increased in oesophageal cancer patients who received neoadjuvant CCRT. Further studies with more cases are necessary to validate these findings.
This paper discusses the value of context in theory development in information systems (IS) research. We examine how prior research has incorporated context in theorizing and develop a framework to ...classify existing approaches to contextualization. In addition, we expound on a decomposition approach to contextualization and put forth a set of guidelines for developing context-specific models. We illustrate the application of the guidelines by constructing and comparing various context-specific variations of the technology acceptance model (TAM)-i.e., the decomposed TAM that incorporates interaction effects between context-specific factors, the extended TAM with context-specific antecedents, and the integrated TAM that incorporates mediated moderation and moderated mediation effects of context-specific factors. We tested the models on 972 individuals in two technology usage contexts: a digital library and an agile Web portal. The results show that the decomposed TAM provides a better understanding of the contexts by revealing the direct and interaction effects of context-specific factors on behavioral intention that are not mediated by the TAM constructs of perceived usefulness and perceived ease of use. This work contributes to the ongoing discussion about the importance of context in theory development and provides guidance for context-specific theorizing in IS research.
Galectin-1 (Gal-1), a homodimeric prototype of the galectins with a single carbohydrate-recognition domain, was recently identified as being overexpressed in tumor-associated capillary endothelial ...cells. The role of Gal-1 in endothelial cellular functions and the mechanism of action of Gal-1 remain unknown. Neuropilin-1 (NRP1) is a neuronal receptor that mediates repulsive growth cone guidance, and NRP1 functions in endothelial cells as a coreceptor (with vascular endothelial growth factor receptors (VEGFRs)) for VEGF(165). In this study, we found that Gal-1 was overexpressed in the tumor-associated endothelial cells of oral squamous cell carcinomas (P<0.001). Gal-1 increased the proliferation and adhesion of endothelial cells, and enhanced cell migration in combination with VEGF(165). Surprisingly, Gal-1 selectively bound NRP1 via the carbohydrate-recognition domain, but did not bind VEGFR-1, VEGFR-2 or VEGFR-3. The Gal-1-NRP1 interaction mediated the migration and adhesion of endothelial cells. The binding of Gal-1 to NRP1 enhanced VEGFR-2 phosphorylation and stimulated the activation of the mitogen activated protein (MAP) kinases SAPK1/JNK (stress activated protein kinase-1/c-Jun NH2-terminal kinase). These findings show, for the first time, that Gal-1 can directly bind to NRP1 on endothelial cells, and can promote the NRP1/VEGFR-2-mediated signaling pathway as well as NRP1-mediated biological activities.
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