760 research outputs found

    Типовая учебная программа по учебной дисциплине для специальности1-21 02 01 Философия

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    This article studies the extent to which corporate entrepreneurial intentions are enacted differently by academic and non-academic entrepreneurs. Using constructs from cognitive research and exploiting the theory of institutional logics, we observe that academic entrepreneurs, notwithstanding their engagement in entrepreneurship, still implement their corporate entrepreneurial intentions acting in accordance with the academic institutional environment to which they belong. Using a matched-pairs research design, our results show that academic entrepreneurs (compared to non- academic ones) leverage their awareness of technical competencies significantly more and their entrepreneurial self-efficacy and awareness of managerial skills considerably less. We discuss the theoretical and managerial implications related to how cognitive and institutional factors interact to foster entrepreneurial value in newly established firms.This article studies the extent to which corporate entrepreneurial intentions are enacted differently by academic and non-academic entrepreneurs. Using constructs from cognitive research and exploiting the theory of institutional logics, we observe that academic entrepreneurs, notwithstanding their engagement in entrepreneurship, still implement their corporate entrepreneurial intentions acting in accordance with the academic institutional environment to which they belong. Using a matched-pairs research design, our results show that academic entrepreneurs (compared to non-academic ones) leverage their awareness of technical competencies significantly more and their entrepreneurial self-efficacy and awareness of managerial skills considerably less. We discuss the theoretical and managerial implications related to how cognitive and institutional factors interact to foster entrepreneurial value in newly established firms

    MiR-33a Controls hMSCS Osteoblast Commitment Modulating the Yap/Taz Expression Through EGFR Signaling Regulation

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    Mesenchymal stromal cells (hMSCs) display a pleiotropic function in bone regeneration. The signaling involved in osteoblast commitment is still not completely understood, and that determines the failure of current therapies being used. In our recent studies, we identified two miRNAs as regulators of hMSCs osteoblast differentiation driving hypoxia signaling and cytoskeletal reorganization. Other signalings involved in this process are epithelial to mesenchymal transition (EMT) and epidermal growth factor receptor (EGFR) signalings through the regulation of Yes-associated protein (YAP)/PDZ-binding motif (TAZ) expression. In the current study, we investigated the role of miR-33a family as a (i) modulator of YAP/TAZ expression and (ii) a regulator of EGFR signaling during osteoblast commitments. Starting from the observation on hMSCs and primary osteoblast cell lines (Nh-Ost) in which EMT genes and miR-33a displayed a specific expression, we performed a gain and loss of function study with miR-33a-5p and 3p on hMSCs cells and Nh-Ost. After 24 h of transfections, we evaluated the modulation of EMT and osteoblast genes expression by qRT-PCR, Western blot, and Osteoimage assays. Through bioinformatic analysis, we identified YAP as the putative target of miR-33a-3p. Its role was investigated by gain and loss of function studies with miR-33a-3p on hMSCs; qRT-PCR and Western blot analyses were also carried out. Finally, the possible role of EGFR signaling in YAP/TAZ modulation by miR-33a-3p expression was evaluated. Human MSCs were treated with EGF-2 and EGFR inhibitor for different time points, and qRT-PCR and Western blot analyses were performed. The above-mentioned methods revealed a balance between miR-33a-5p and miR-33a-3p expression during hMSCs osteoblast differentiation. The human MSCs phenotype was maintained by miR-33a-5p, while the maintenance of the osteoblast phenotype in the Nh-Ost cell model was permitted by miR-33a-3p expression, which regulated YAP/TAZ through the modulation of EGFR signaling. The inhibition of EGFR blocked the effects of miR-33a-3p on YAP/TAZ modulation, favoring the maintenance of hMSCs in a committed phenotype. A new possible personalized therapeutic approach to bone regeneration was discussed, which might be mediated by customizing delivery of miR-33a in simultaneously targeting EGFR and YAP signaling with combined use of drugs

    Multimodal Emotion Recognition with Modality-Pairwise Unsupervised Contrastive Loss

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    Emotion recognition is involved in several real-world applications. With an increase in available modalities, automatic understanding of emotions is being performed more accurately. The success in Multimodal Emotion Recognition (MER), primarily relies on the supervised learning paradigm. However, data annotation is expensive, time-consuming, and as emotion expression and perception depends on several factors (e.g., age, gender, culture) obtaining labels with a high reliability is hard. Motivated by these, we focus on unsupervised feature learning for MER. We consider discrete emotions, and as modalities text, audio and vision are used. Our method, as being based on contrastive loss between pairwise modalities, is the first attempt in MER literature. Our end-to-end feature learning approach has several differences (and advantages) compared to existing MER methods: i) it is unsupervised, so the learning is lack of data labelling cost; ii) it does not require data spatial augmentation, modality alignment, large number of batch size or epochs; iii) it applies data fusion only at inference; and iv) it does not require backbones pre-trained on emotion recognition task. The experiments on benchmark datasets show that our method outperforms several baseline approaches and unsupervised learning methods applied in MER. Particularly, it even surpasses a few supervised MER state-of-the-art

    Institutional determinants of university spin-off quantity and quality: a longitudinal, multilevel, cross-country study

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    The creation of spin-off firms from universities is seen as an important mechanism for the commercialization of research, and hence the overall contribution from universities to technological development and economic growth. Governments and universities are seeking to develop framework conditions that are conductive to spin-off creation. The most prevalent of such initiatives are legislative changes at national level and the establishment of technology transfer offices at university level. The effectiveness of such initiatives is debated, but empirical evidence is limited. In this paper, we analyze the full population of universities in Italy, Norway, and the UK; three countries adopting differing approaches to framework conditions, to test whether national- and university-level initiatives have an influence on the number of spin-offs created and the quality of these spin-offs. Building on institutional theory and using multilevel analysis, we find that changes in the institutional framework conditions at both national and university levels are conductive to the creation of more spin-offs, but that the increase in quantity is at the expense of the quality of these firms. Hence, the effect of such top–down changes in framework conditions on the economic impact from universities seems to be more symbolic than substantive

    How miR-31-5p and miR-33a-5p Regulates SP1/CX43 Expression in Osteoarthritis Disease: Preliminary Insights

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    Osteoarthritis (OA) is a degenerative bone disease that involved micro and macro-environment of joints. To date, there are no radical curative treatments for OA and novel therapies are mandatory. Recent evidence suggests the role of miRNAs in OA progression. In our previous studies, we demonstrated the role of miR-31-5p and miR-33a families in different bone regeneration signaling. Here, we investigated the role of miR-31-5p and miR-33a-5p in OA progression. A different expression of miR-31-5p and miR-33a-5p into osteoblasts and chondrocytes isolated from joint tissues of OA patients classified in based on different Kellgren and Lawrence (KL) grading was highlighted; and through a bioinformatic approach the common miRNAs target Specificity proteins (Sp1) were identified. Sp1 regulates the expression of gap junction protein Connexin43 (Cx43), which in OA drives the modification of (i) osteoblasts and chondrocytes genes expression, (ii) joint inflammation cytokines releases and (iii) cell functions. Concerning this, thanks to gain and loss of function studies, the possible role of Sp1 as a modulator of CX43 expression through miR-31-5p and miR-33a-5p action was also evaluated. Finally, we hypothesize that both miRNAs cooperate to modulate the expression of SP1 in osteoblasts and chondrocytes and interfering, consequently, with CX43 expression, and they might be further investigated as new possible biomarkers for OA

    Multiple Myeloma-Derived Extracellular Vesicles Induce Osteoclastogenesis through the Activation of the XBP1/IRE1\u3b1 Axis

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    Bone disease severely affects the quality of life of over 70% of multiple myeloma (MM) patients, which daily experience pain, pathological fractures, mobility issues and an increased mortality. Recent data have highlighted the crucial role of the endoplasmic reticulum-associated unfolded protein response (UPR) in malignant transformation and tumor progression; therefore, targeting of UPR-related molecules may open novel therapeutic avenues. Endoplasmic reticulum (ER) stress and UPR pathways are constitutively activated in MM cells, which are characterized by an increased protein turnover as a consequence of high production of immunoglobulins and high rates of protein synthesis. A great deal of scientific data also evidenced that a mild activation of UPR pathway can regulate cellular differentiation. Our previous studies revealed that MM cell-derived small extracellular vesicle (MM-EV) modulated osteoclasts (OCs) function and induced OCs differentiation. Here, we investigated the role of the UPR pathway, and in particular of the IRE1\u3b1/XBP1 axis, in osteoclastogenesis induced by MM-EVs. By proteomic analysis, we identified UPR signaling molecules as novel MM-EV cargo, prompting us to evaluate the effects of the MM-EVs on osteoclastogenesis through UPR pathway. MM-EVs administration in a murine macrophage cell line rapidly induced activation of IRE1\u3b1 by phosphorylation in S724; accordingly, Xbp1 mRNA splicing was increased and the transcription of NFATc1, a master transcription factor for OCs differentiation, was activated. Some of these results were also validated using both human primary OC cultures and MM-EVs from MM patients. Notably, a chemical inhibitor of IRE1\u3b1 (GSK2850163) counteracted MM-EV-triggered OC differentiation, hampering the terminal stages of OCs differentiation and reducing bone resorption

    Serial Ultrasound Assessment of Diaphragmatic Function and Clinical Outcome in Patients with Amyotrophic Lateral Sclerosis.

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    Background: Ultrasound (US) evaluation of the diaphragm may be a non-volitional useful tool in the clinical management of patients with ALS. Aim of the present study was then to evaluate the impact of serial assessment of ΔTmax index on clinical outcomes during the follow-up in these patients and to correlate non-volitional US indices and other volitional measures with these outcomes. Methods: A cohort of 39 consecutive patients with ALS was followed up to 24 months. At baseline and every 3-month spirometry (forced vital capacity-FVC), sniff inspiratory nasal pressure (SNIP), and US of the diaphragm (ΔTdi and ΔTmax) were recorded. These parameters were correlated with clinical outcomes (hypercapnia, nocturnal hypoventilation, NIV start in the following 6 month, and death within 1 year). Results: The occurrence of ΔTmax >0.75 during follow-up increased the risk for NIV (HR=5.6, p=0.001) and death (HR=3.7, p=0.0001) compared with patients with stable lower values. The evidence of diaphragmatic dysfunction, i.e. ΔTmax >0.75, occurs 3.2 month earlier than the onset of NIV. Moreover, ΔTmax >0.75 correlated with onset of nocturnal hypoventilation, NIV initiation within 6 months, and death within 12 months, similarly to FVC <50% predicted and better than other functional indices. Conclusions: Serial monitoring of diaphragmatic ΔTmax by US may be useful to predict initiation of NIV and death in patients with ALS. The occurrence of an abnormal ΔTmax value in the follow-up precedes the decision for starting NIV

    Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation

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    Bone disease is the most frequent complication in multiple myeloma (MM) resulting in osteolytic lesions, bone pain, hypercalcemia and renal failure. In MM bone disease the perfect balance between bone-resorbing osteoclasts (OCs) and bone-forming osteoblasts (OBs) activity is lost in favour of OCs, thus resulting in skeletal disorders. Since exosomes have been described for their functional role in cancer progression, we here investigate whether MM cell-derived exosomes may be involved in OCs differentiation. We show that MM cells produce exosomes which are actively internalized by Raw264.7 cell line, a cellular model of osteoclast formation. MM cell-derived exosomes positively modulate pre-osteoclast migration, through the increasing of CXCR4 expression and trigger a survival pathway. MM cell-derived exosomes play a significant pro-differentiative role in murine Raw264.7 cells and human primary osteoclasts, inducing the expression of osteoclast markers such as Cathepsin K (CTSK), Matrix Metalloproteinases 9 (MMP9) and Tartrate-resistant Acid Phosphatase (TRAP). Pre-osteoclast treated with MM cell-derived exosomes differentiate in multinuclear OCs able to excavate authentic resorption lacunae. Similar results were obtained with exosomes derived from MM patient's sera. Our data indicate that MM-exosomes modulate OCs function and differentiation. Further studies are needed to identify the OCs activating factors transported by MM cell-derived exosomes

    GIANO and HARPS-N together: towards an Earth-mass detection instrument

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    This article describes the works we are doing for modifying the interface between the high resolution infrared spectrograph GIANO (0.97-2.4 micron) and the TNG telescope, passing from a fiber feed configuration to the original design of a direct light-feeding from the telescope to the spectrograph. So doing the IR spectrograph, GIANO, will work in parallel to HARPS-N spectrometer (0.38-0.70 micron), the visible high resolution spectrograph, thanks to a new telescope interface based on a dichroic window that simultaneously feeds the two instrumentes: this is GIARPS (GIAno and haRPS). The scientific aims of this project are to improve the radial velocity accuracy achievable with GIANO, down to a goal of 1 m/s, the value necessary to detect Earth-mass planets on habitable orbits around late-M stars, to implement simultaneous observations with Harps-N and GIANO optimizing the study of planets around cool stars. The very broad wavelengths range is particularly important to discriminate false radial velocity signals caused by stellar activity. We therefore include several absorption cells with different mixtures of gases and a stabilized Fabry Perot cavity, necessary to have absorption lines over the 0.97-2.4 microns range covered by GIANO. The commissioning of GIARPS is scheduled by the end of 2016
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