667 research outputs found

    Annexin 2A sustains glioblastoma cell dissemination and proliferation.

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    Glioblastoma (GBM) is the most devastating tumor of the brain, characterized by an almost inevitable tendency to recur after intensive treatments and a fatal prognosis. Indeed, despite recent technical improvements in GBM surgery, the complete eradication of cancer cell disseminated outside the tumor mass still remains a crucial issue for glioma patients management. In this context, Annexin 2A (ANXA2) is a phospholipid-binding protein expressed in a variety of cell types, whose expression has been recently associated with cell dissemination and metastasis in many cancer types, thus making ANXA2 an attractive putative regulator of cell invasion also in GBM.Here we show that ANXA2 is over-expressed in GBM and positively correlates with tumor aggressiveness and patient survival. In particular, we associate the expression of ANXA2 to a mesenchymal and metastatic phenotype of GBM tumors. Moreover, we functionally characterized the effects exerted by ANXA2 inhibition in primary GBM cultures, demonstrating its ability to sustain cell migration, matrix invasion, cytoskeletal remodeling and proliferation. Finally, we were able to generate an ANXA2-dependent gene signature with a significant prognostic potential in different cohorts of solid tumor patients, including GBM.In conclusion, we demonstrate that ANXA2 acts at multiple levels in determining the disseminating and aggressive behaviour of GBM cells, thus proving its potential as a possible target and strong prognostic factor in the future management of GBM patients

    Memory effect in silicon time-gated single-photon avalanche diodes

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    We present a comprehensive characterization of the memory effect arising in thin-junction silicon Single-Photon Avalanche Diodes (SPADs) when exposed to strong illumination. This partially unknown afterpulsing-like noise represents the main limiting factor when time-gated acquisitions are exploited to increase the measurement dynamic range of very fast (picosecond scale) and faint (single-photon) optical signals following a strong stray one. We report the dependences of this unwelcome signal-related noise on photon wavelength, detector temperature, and biasing conditions. Our results suggest that this so-called "memory effect" is generated in the deep regions of the detector, well below the depleted region, and its contribution on detector response is visible only when time-gated SPADs are exploited to reject a strong burst of photons

    The Effects of Business Failure Experience on Successive Entrepreneurial Engagements: An Evolutionary Phase Model

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    This study draws insights from the literatures on entrepreneurial learning from failure and organizational imprinting to develop an evolutionary phase model to explain how prior business failure experience influences successive newly started businesses. Using multiple case studies of entrepreneurs located in an institutionally developing society in Sub-Sahara Africa, we uncover four distinctive phases of post-entrepreneurial business failure: grief and despair, transition, formation and legacy phases. We find that while the grieving and transition phases entailed processes of reflecting and learning lessons from the business failure experiences, the formation and legacy phases involve processes of imprinting entrepreneurs’ experiential knowledge on their successive new start-up firms. We conclude by outlining a number of fruitful avenues for future research

    The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

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    Background: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard care for locally advanced rectal cancer, but tumour response to CRT and disease outcome are variable. The current study aimed to investigate the effectiveness of plasma telomerase reverse transcriptase (TERT) levels in predicting tumour response and clinical outcome. Methods: 176 rectal cancer patients were included. Plasma samples were collected at baseline (before CRT\ubcT0), 2 weeks after CRT was initiated (T1), post-CRT and before surgery (T2), and 4\u20138 months after surgery (T3) time points. Plasma TERT mRNA levels and total cell-free RNA were determined using real-time PCR. Results: Plasma levels of TERT were significantly lower at T2 (Po0.0001) in responders than in non-responders. Post-CRT TERT levels and the differences between pre- and post-CRT TERT levels independently predicted tumour response, and the prediction model had an area under curve of 0.80 (95% confidence interval (CI) 0.73\u20130.87). Multiple analysis demonstrated that patients with detectable TERT levels at T2 and T3 time points had a risk of disease progression 2.13 (95% CI 1.10\u20134.11)-fold and 4.55 (95% CI 1.48\u201313.95)-fold higher, respectively, than those with undetectable plasma TERT levels. Conclusions: Plasma TERT levels are independent markers of tumour response and are prognostic of disease progression in rectal cancer patients who undergo neoadjuvant therapy

    ENTREPRENEURIAL AND MARKET-ORIENTED ACTIVITIES, FINANCIAL CAPITAL, ENVIRONMENT TURBULENCE, AND EXPORT PERFORMANCE IN AN EMERGING ECONOMY

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    This study examines the impact of the simultaneous implementation of entrepreneurial and market-oriented export activities on export success and whether this relationship depends on levels of financial capital and market environment turbulence. The findings from a study of 164 Ghanaian exporting small and medium-sized enterprises (SMEs) indicate that high levels of both entrepreneurial and market orientation generate better export performance. The relationship is stronger when firms have greater financial capital and operate in more turbulent export market environments. These results extend existing knowledge of how SMEs can improve export performance by seeking fit between firm-specific capabilities and external environment conditions

    Evaluation of foliar resistance to downy mildew in different cv. Albariño clones

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    Resistance to downy mildew was studied in different Vitis vinifera L. cv. Albariño clones belonging to the collection of the Mision Biológica de Galicia, CSIC (Spain). V. riparia, V. vinifera cv. Solaris and V. vinifera cv. Müller-Thurgau were used as controls. Plants were inoculated with Plasmospora viticola in the laboratory using the leaf disc, whole leaf and whole plant techniques. The results were compared with those obtained in the field for the same Albariño clones. The most susceptible group of clones included MBG-2, MBG-14, MBG-12 and MBG-9, while MBG-13, MBG-3 and MBG-6 formed the most resistant group. The remaining clones showed intermediate resistance. These results coincide with observations made in the field. The resistance observed in MBG-12 could have been generated from in vitro culture, because this induces changes in the downy mildew resistance.

    Optimisation of ITER Nb3Sn CICCs for coupling loss, transverse electromagnetic load and axial thermal contraction

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    The ITER cable-in-conduit conductors (CICCs) are built up from sub-cable bundles, wound in different stages, which are twisted to counter coupling loss caused by time-changing external magnet fields. The selection of the twist pitch lengths has major implications for the performance of the cable in the case of strain sensitive superconductors, i.e. Nb3Sn, as the electromagnetic and thermal contraction loads are large but also for the heat load from the AC coupling loss. Reduction of the transverse load and warm-up cool-down degradation can be reached by applying longer twist pitches in a particular sequence for the sub-stages, offering a large cable transverse stiffness, adequate axial flexibility and maximum allowed lateral strand support. Analysis of short sample (TF conductor) data reveals that increasing the twist pitch can lead to a gain of the effective axial compressive strain of more than 0.3 % with practically no degradation from bending. For reduction of the coupling loss, specific choices of the cabling twist sequence are needed with the aim to minimize the area of linked strands and bundles that are coupled and form loops with the applied changing magnetic field, instead of simply avoiding longer pitches. In addition we recommend increasing the wrap coverage of the CS conductor from 50 % to at least 70 %. The models predict significant improvement against strain sensitivity and substantial decrease of the AC coupling loss in Nb3Sn CICCs, but also for NbTi CICCs minimization of the coupling loss can be achieved. Although the success of long pitches to transverse load degradation was already demonstrated, the prediction of the combination with low coupling loss needs to be validated by a short sample test.Comment: to be published in Supercond Sci Techno
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