509 research outputs found

    (De)centralized governance and the value of platform-based new ventures: The moderating role of teams and transparency

    Get PDF
    This is the final version. Available from Springer via the DOI in this record. Drawing on institutional and demand-side perspectives, we investigate performance implications of (de)centralized governance modes in platform-based new ventures, and the conditions under which (de)centralization generates more value. Using a sample of 1,431 Initial Coin Offerings (ICOs), a new source of entrepreneurial finance, we find that centralization of decision-making is positively associated with platforms’ market value. Further, we consider how platform characteristics affect this relationship, finding that both the presence of an experienced Chief Technology Officer (CTO) and project transparency negatively moderate the positive relationship between centralization and market value. Thus, decentralized platforms need leaders with technical experience and project transparency to generate more value. Overall, this study provides a better understanding of the boundary conditions that increase the value of (de)centralized governance. Plain English Summary - This study investigates how different governance structures impact the market value of new blockchain-based ventures that conduct Initial Coin Offerings (ICOs). We explore the roles of centralized and decentralized decision-making and how these structures affect platform performance. Our findings show that centralized governance, where decision-making is concentrated, tends to increase a platform’s market value. However, having an experienced Chief Technology Officer (CTO) and clear project transparency can reduce the reliance on centralization. This implies that decentralized platforms can also achieve high market value if they have transparent processes and skilled leaders who can manage the technical aspects. The primary implication for practice is that new blockchain platforms should focus on hiring experienced technical leaders and ensuring transparency in their projects to attract investors and customers.Università di Pis

    Cyclin A2 Mutagenesis Analysis: A New Insight into CDK Activation and Cellular Localization Requirements

    Get PDF
    Cyclin A2 is essential at two critical points in the somatic cell cycle: during S phase, when it activates CDK2, and during the G2 to M transition when it activates CDK1. Based on the crystal structure of Cyclin A2 in association with CDKs, we generated a panel of mutants to characterize the specific amino acids required for partner binding, CDK activation and subcellular localization. We find that CDK1, CDK2, p21, p27 and p107 have overlapping but distinct requirements for association with this protein. Our data highlight the crucial importance of the N-terminal α helix, in conjunction with the α3 helix within the cyclin box, in activating CDK. Several Cyclin A2 mutants selectively bind to either CDK1 or CDK2. We demonstrate that association of Cyclin A2 to proteins such as CDK2 that was previously suggested as crucial is not a prerequisite for its nuclear localization, and we propose that the whole protein structure is involved

    Relocation to get venture capital : a resource dependence perspective

    Get PDF
    This is the author accepted manuscript. The final version is available from SAGE via the DOI in this record.Using a resource dependence perspective, we theorize and show that non-venture-capital-backed ventures founded in U.S. states with a lower availability of venture capital (VC) are more likely to relocate to California (CA) or Massachusetts (MA)—the two VC richest states—compared to ventures founded in states with a greater availability of VC. Moreover, controlling for self-selection, ventures that relocate to CA or MA subsequently have a greater probability of attracting initial VC compared to ventures that stay in their home state. We discuss the implications for theory, future research, and practice

    Vibrotactile Feedback for Brain-Computer Interface Operation

    Get PDF
    To be correctly mastered, Brain-Computer Interfaces (BCIs) need an uninterrupted flow of feedback to the user. This feedback is usually delivered through the visual channel. Our aim is to explore the benefits of vibrotactile feedback during users� training and control of EEG-based BCI applications. A protocol for delivering vibrotactile feedback, including specific hardware and software arrangements, was specified. In three studies with 33 subjects (including 3 with spinal cord injury) we compared vibrotactile and visual feedback, addressing: (I) the feasibility of subjects� training to master their EEG rhythms using tactile feedback; (II) the compatibility of this form of feedback in presence of a visual distracter; and (III) the performance in presence of a complex visual task on the same (visual) or different (tactile) sensory channel. The stimulation protocol we developed supports a general usage of the tactors; preliminary experimentations. All studies indicated that the vibrotactile channel can function as a valuable feedback modality with reliability comparable to the classical visual feedback. Advantages of using a vibrotactile feedback emerged when the visual channel was highly loaded by a complex task. In all experiments, vibrotactile feedback felt (after some training) more natural for both controls and SCI users

    Vibrotactile Feedback in the Context of Mu-Rhythm based BCI

    Get PDF
    Brain-Computer Interfaces (BCIs) need an uninterrupted flow of feedback to the user, which is usually delivered through the visual channel. Our aim is to explore the benefits of vibrotactile feedback during users� training and control of EEG-based BCI applications. An experimental setup for delivery of vibrotactile feedback, including specific hardware and software arrangements, was specified. We compared vibrotactile and visual feedback, addressing the performance in presence of a complex visual task on the same (visual) or different (tactile) sensory channel. The preliminary experimental setup included a simulated BCI control. in which all parts reflected the computational and actuation process of an actual BCI, except the souce, which was simulated using a �noisy� PC mouse. Results indicated that the vibrotactile channel can function as a valuable feedback modality with reliability comparable to the classical visual feedback. Advantages of using a vibrotactile feedback emerged when the visual channel was highly loaded by a complex task

    The origins and development of Zuwīla, Libyan Sahara: an archaeological and historical overview of an ancient oasis town and caravan centre

    Get PDF
    Zuwīla in southwestern Libya (Fazzān) was one of the most important early Islamic centres in the Central Sahara, but the archaeological correlates of the written sources for it have been little explored. This paper brings together for the first time a detailed consideration of the relevant historical and archaeological data, together with new AMS radiocarbon dates from several key monuments. The origins of the settlement at Zuwīla were pre-Islamic, but the town gained greater prominence in the early centuries of Arab rule of the Maghrib, culminating with the establishment of an Ibāḍī state ruled by the dynasty of the Banū Khaṭṭāb, with Zuwīla its capital. The historical sources and the accounts of early European travellers are discussed and archaeological work at Zuwīla is described (including the new radiocarbon dates). A short gazetteer of archaeological monuments is provided as an appendix. Comparisons and contrasts are also drawn between Zuwīla and other oases of the ash-Sharqiyāt region of Fazzān. The final section of the paper presents a series of models based on the available evidence, tracing the evolution and decline of this remarkable site

    The RIP140 Gene Is a Transcriptional Target of E2F1

    Get PDF
    RIP140 is a transcriptional coregulator involved in energy homeostasis and ovulation which is controlled at the transcriptional level by several nuclear receptors. We demonstrate here that RIP140 is a novel target gene of the E2F1 transcription factor. Bioinformatics analysis, gel shift assay, and chromatin immunoprecipitation demonstrate that the RIP140 promoter contains bona fide E2F response elements. In transiently transfected MCF-7 breast cancer cells, the RIP140 promoter is transactivated by overexpression of E2F1/DP1. Interestingly, RIP140 mRNA is finely regulated during cell cycle progression (5-fold increase at the G1/S and G2/M transitions). The positive regulation by E2F1 requires sequences located in the proximal region of the promoter (−73/+167), involves Sp1 transcription factors, and undergoes a negative feedback control by RIP140. Finally, we show that E2F1 participates in the induction of RIP140 expression during adipocyte differentiation. Altogether, this work identifies the RIP140 gene as a new transcriptional target of E2F1 which may explain some of the effect of E2F1 in both cancer and metabolic diseases

    Immunocytochemical determination of the subcellular distribution of ascorbate in plants

    Get PDF
    Ascorbate is an important antioxidant in plants and fulfills many functions related to plant defense, redox signaling and modulation of gene expression. We have analyzed the subcellular distribution of reduced and oxidized ascorbate in leaf cells of Arabidopsis thaliana and Nicotiana tabacum by high-resolution immuno electron microscopy. The accuracy and specificity of the applied method is supported by several observations. First, preadsorption of the ascorbate antisera with ascorbic acid or dehydroascorbic acid resulted in the reduction of the labeling to background levels. Second, the overall labeling density was reduced between 50 and 61% in the ascorbate-deficient Arabidopsis mutants vtc1-2 and vtc2-1, which correlated well with biochemical measurements. The highest ascorbate-specific labeling was detected in nuclei and the cytosol whereas the lowest levels were found in vacuoles. Intermediate labeling was observed in chloroplasts, mitochondria and peroxisomes. This method was used to determine the subcellular ascorbate distribution in leaf cells of plants exposed to high light intensity, a stress factor that is well known to cause an increase in cellular ascorbate concentration. High light intensities resulted in a strong increase in overall labeling density. Interestingly, the strongest compartment-specific increase was found in vacuoles (fourfold) and in plastids (twofold). Ascorbate-specific labeling was restricted to the matrix of mitochondria and to the stroma of chloroplasts in control plants but was also detected in the lumen of thylakoids after high light exposure. In summary, this study reveals an improved insight into the subcellular distribution of ascorbate in plants and the method can now be applied to determine compartment-specific changes in ascorbate in response to various stress situations

    Galectin-3 Facilitates Cell Motility in Gastric Cancer by Up-Regulating Protease-Activated Receptor-1(PAR-1) and Matrix Metalloproteinase-1(MMP-1)

    Get PDF
    BACKGROUND: Galectin-3 is known to regulate cancer metastasis. However, the underlying mechanism has not been defined. Through the DNA microarray studies after galectin-3 silencing, we demonstrated here that galectin-3 plays a key role in up-regulating the expressions of protease-activated receptor-1 (PAR-1) and matrix metalloproteinase-1 (MMP-1) PAR-1 thereby promoting gastric cancer metastasis. METHODOLOGY/PRINCIPAL FINDINGS: We examined the expression levels of Galectin-3, PAR-1, and MMP-1 in gastric cancer patient tissues and also the effects of silencing these proteins with specific siRNAs and of over-expressing them using specific lenti-viral constructs. We also employed zebrafish embryo model for analysis of in vivo gastric cancer cell invasion. These studies demonstrated that: a) galectin-3 silencing decreases the expression of PAR-1. b) galectin-3 over-expression increases cell migration and invasion and this increase can be reversed by PAR-1 silencing, indicating that galectin-3 increases cell migration and invasion via PAR-1 up-regulation. c) galectin-3 directly interacts with AP-1 transcriptional factor, and this complex binds to PAR-1 promoter and drives PAR-1 transcription. d) galectin-3 also amplifies phospho-paxillin, a PAR-1 downstream target, by increasing MMP-1 expression. MMP-1 silencing blocks phospho-paxillin amplification and cell invasion caused by galectin-3 over-expression. e) Silencing of either galectin-3, PAR-1 or MMP-1 significantly reduced cell migration into the vessels in zebrafish embryo model. f) Galectin-3, PAR-1, and MMP-1 are highly expressed and co-localized in malignant tissues from gastric cancer patients. CONCLUSIONS/SIGNIFICANCE: Galectin-3 plays the key role of activating cell surface receptor through production of protease and boosts gastric cancer metastasis. Galectin-3 has the potential to serve as a useful pharmacological target for prevention of gastric cancer metastasis
    corecore