108 research outputs found

    Dividing the ICO Jungle: Extracting and Evaluating Design Archetypes

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    The sale of blockchain-based digital tokens as a novel funding mechanism, referred to as initial coin offerings (ICO), has grown exponentially, resulting in $12bn raised globally during the first half of 2018. Due to the novelty of the phenomenon, the concept is not yet entirely understood. Existing research provides first insights into ICO endeavors and design only. To date, comprehensive and in-depth analyses of ICO design archetypes to better understand prevailing ICO characteristics are missing. We bridge this gap by enriching an existing ICO taxonomy and applying a cluster analysis to identify predominant ICO archetypes. As a result, we identify five ICO design archetypes: the average ICO, the liberal ICO, the visionary ICO, the compliant ICO, and the native ICO. We thereby contribute to a comprehensive and in-depth understanding of the ICO phenomenon and its implications. Further, we offer practitioners tangible design suggestions for future ICOs

    Detection of small tendon lesions by sonoelastographic visualization of strain profile differences: initial experiences

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    Purpose: To assess the capability of a commercial sonoelastography system to detect small tendon lesions by quantitative analysis of elastogram profiles. Materials and methods: Strips of equine digital flexor tendons were used to model small human tendons. Two tendons were examined. From each tendon, six unmodified tendon strips (controls) and six tendon strips with a central defect of the same tendons were compared. The tendon strips were placed under a physiological tensile strain of 5%. Sonoelastographic visualization of the strain profile was performed. Regions of interest (ROI) were defined left and right of the tendon defects. Average tissue strains in these ROI were compared with tissue strain in controls. Results: In the first series of experiments, there was a significant (p = 0.011) difference in the strain profile in regions proximal and distal to the tendon lesions compared with the respective tendon areas in the control tendon strips. In a second series of experiments, similar trends were observed, but the differences were not significant (p = 0.824). Conclusion: Even under carefully controlled experimental conditions using computational post-processing of sonoelastograms, tendon lesions could only be partially detected within elastograms from a clinical sonoelastography system. The ability to detect differences in some strain profiles indicates that tensile sonoelastography has the potential to identify small tendon lesions (such as those in the hand), but that substantial improvements with respect to quantitative analysis are required to make such measures diagnostically relevan

    Tarzan and chain: exploring the ICO jungle and evaluating design archetypes

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    The phenomenon of a blockchain use case called initial coin offering (ICO) is drawing increasing attention as a novel funding mechanism. ICO is a crowdfunding type that utilizes blockchain tokens to allow for truly peer-to-peer investments. Although more than \$7bn has been raised globally via ICOs as at 2018, the concept and its implications are not yet entirely understood. The research lags behind in providing in-depth analyses of ICO designs and their long-term success. We address this research gap by developing an ICO taxonomy, applying a cluster analysis to identify prevailing ICO archetypes, and providing an outlook on the token value market performance for individual archetypes. We identify five ICO design archetypes and display their secondary market development from both a short-term and a long-term perspective. We contribute to an in-depth understanding of ICOs and their implications. Further, we offer practitioners tangible design and success indications for future ICOs

    GREENLION Project: Advanced Manufacturing Processes for Low Cost Greener Li-Ion Batteries

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    GREENLION is a Large Scale Collaborative Project within the FP7 (GC.NMP.2011-1) leading to the manufacturing of greener and cheaper Li-Ion batteries for electric vehicle applications via the use of water soluble, fluorine-free, high thermally stable binders, which would eliminate the use of VOCs and reduce the cell assembly cost. The project has 6 key objectives: (i) development of new active and inactive battery materials viable for water processes (green chemistry); (ii) development of innovative processes (coating from aqueous slurries) capable of reducing electrode production cost and avoid environmental pollution; (iii) development of new assembly procedures (including laser cutting and high temperature pre-treatment) capable of substantially reduce the time and the cost of cell fabrication; (iv) lighter battery modules with easier disassembly through eco-designed bonding techniques; (v) waste reduction, which, by making use of the watersolubility of the binder, allows the extensive recovery of the active and inactive battery materials; and (vi) development of automated process and construction of fully integrated battery module for electric vehicle applications with optimized electrodes, cells, and other ancillaries. Achievements during the first 18 months of the project, especially on materials development and water-based electrode fabri cation are reported herein

    Subtype-specific differentiation of cardiac pacemaker cell clusters from human induced pluripotent stem cells

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    Background: Human induced pluripotent stem cells (hiPSC) harbor the potential to differentiate into diverse cardiac cell types. Previous experimental efforts were primarily directed at the generation of hiPSC-derived cells with ventricular cardiomyocyte characteristics. Aiming at a straightforward approach for pacemaker cell modeling and replacement, we sought to selectively differentiate cells with nodal-type properties. Methods: hiPSC were differentiated into spontaneously beating clusters by co-culturing with visceral endoderm-like cells in a serum-free medium. Subsequent culturing in a specified fetal bovine serum (FBS)-enriched cell medium produced a pacemaker-type phenotype that was studied in detail using quantitative real-time polymerase chain reaction (qRT-PCR), immunocytochemistry, and patch-clamp electrophysiology. Further investigations comprised pharmacological stimulations and co-culturing with neonatal cardiomyocytes. Results: hiPSC co-cultured in a serum-free medium with the visceral endoderm-like cell line END-2 produced spontaneously beating clusters after 10–12 days of culture. The pacemaker-specific genes HCN4, TBX3, and TBX18 were abundantly expressed at this early developmental stage, while levels of sarcomeric gene products remained low. We observed that working-type cardiomyogenic differentiation can be suppressed by transfer of early clusters into a FBS-enriched cell medium immediately after beating onset. After 6 weeks under these conditions, sinoatrial node (SAN) hallmark genes remained at high levels, while working-type myocardial transcripts (NKX2.5, TBX5) were low. Clusters were characterized by regular activity and robust beating rates (70–90 beats/min) and were triggered by spontaneous Ca2+ transients recapitulating calcium clock properties of genuine pacemaker cells. They were responsive to adrenergic/cholinergic stimulation and able to pace neonatal rat ventricular myocytes in co-culture experiments. Action potential (AP) measurements of cells individualized from clusters exhibited nodal-type (63.4%) and atrial-type (36.6%) AP morphologies, while ventricular AP configurations were not observed. Conclusion: We provide a novel culture media-based, transgene-free approach for targeted generation of hiPSC-derived pacemaker-type cells that grow in clusters and offer the potential for disease modeling, drug testing, and individualized cell-based replacement therapy of the SAN

    O MAPA “SOLIDARIEDADE E ASSISTÊNCIA SOCIAL”: LITORAL NORTE (RS) - PANDEMIA COVID-19

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    A Pandemia da COVID-19 ilumina necessidades históricas das trabalhadoras(es) no país, escancara-se a desigualdade e a precarização da vida. Neste momento, ações populares despem as demandas sociais exigindo a presença do Estado Brasileiro, que imbuído da prática neoliberal, aprofunda uma política de destruição de direitos sociais. O contexto exige que as instituições públicas insurjam contra as determinações políticas deste Governo, e nas universidades, que seja fortalecida a relação entre pesquisa, extensão e ensino, sob uma perspectiva popular. Como força somatória a essas ações, pesquisadoras(es) da UFRGS Litoral produziu um mapa articulado à mobilização de solidariedade promovida por lideranças comunitárias na região. Tais movimentações são importantes: a produção do mapa forjado na prática social; o envolvimento expressivo de estudantes; a problematização da ausência dos dados públicos para a análise social e o debate político sobre as estratégias para o enfrentamento da Pandemia. Reconhecemos que a necessidade do isolamento social tem evidenciado: as condições de vida no Litoral Norte/RS e a urgência da universalização das políticas sociais para a consolidação do Sistema Único de Assistência Social. Este trabalho contribui na efervescência dos mapeamentos que se colocam estrategicamente como representações críticas e ao mesmo tempo como mobilizador das lutas sociais, sem perder de vista o fundamento histórico da miséria no Brasil

    Architecture of soil microaggregates: Advanced methodologies to explore properties and functions

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    The functions of soils are intimately linked to their three-dimensional pore space and the associated biogeochemical interfaces, mirrored in the complex structure that developed during pedogenesis. Under stress overload, soil disintegrates into smaller compound structures, conventionally named aggregates. Microaggregates (<250 µm) are recognized as the most stable soil structural units. They are built of mineral, organic, and biotic materials, provide habitats for a vast diversity of microorganisms, and are closely involved in the cycling of matter and energy. However, exploring the architecture of soil microaggregates and their linkage to soil functions remains a challenging but demanding scientific endeavor. With the advent of complementary spectromicroscopic and tomographic techniques, we can now assess and visualize the size, composition, and porosity of microaggregates and the spatial arrangement of their interior building units. Their combinations with advanced experimental pedology, multi-isotope labeling experiments, and computational approaches pave the way to investigate microaggregate turnover and stability, explore their role in element cycling, and unravel the intricate linkage between structure and function. However, spectromicroscopic techniques operate at different scales and resolutions, and have specific requirements for sample preparation and microaggregate isolation; hence, special attention must be paid to both the separation of microaggregates in a reproducible manner and the synopsis of the geography of information that originates from the diverse complementary instrumental techniques. The latter calls for further development of strategies for synlocation and synscaling beyond the present state of correlative analysis. Here, we present examples of recent scientific progress and review both options and challenges of the joint application of cutting-edge techniques to achieve a sophisticated picture of the properties and functions of soil microaggregates

    Spindle assembly checkpoint robustness requires Tpr-mediated regulation of Mad1/Mad2 proteostasis

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    Tpr is a conserved nuclear pore complex (NPC) protein implicated in the spindle assembly checkpoint (SAC) by an unknown mechanism. Here, we show that Tpr is required for normal SAC response by stabilizing Mad1 and Mad2 before mitosis. Tpr coimmunoprecipitated with Mad1 and Mad2 (hereafter designated as Tpr/Mad1/Mad2 or TM2 complex) during interphase and mitosis, and is required for Mad1–c-Mad2 recruitment to NPCs. Interestingly, Tpr was normally undetectable at kinetochores and dispensable for Mad1, but not for Mad2, kinetochore localization, which suggests that SAC robustness depends on Mad2 levels at kinetochores. Protein half-life measurements demonstrate that Tpr stabilizes Mad1 and Mad2, ensuring normal Mad1–c-Mad2 production in an mRNA- and kinetochore-independent manner. Overexpression of GFP-Mad2 restored normal SAC response and Mad2 kinetochore levels in Tpr-depleted cells. Mechanistically, we provide evidence that Tpr might spatially regulate SAC proteostasis through the SUMO-isopeptidases SENP1 and SENP2 at NPCs. Thus, Tpr is a kinetochore-independent, rate-limiting factor required to mount and sustain a robust SAC response

    Restriction of HIV-1 Replication in Monocytes Is Abolished by Vpx of SIVsmmPBj

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    Background: Human primary monocytes are refractory to infection with the human immunodeficiency virus 1 (HIV-1) or transduction with HIV-1-derived vectors. In contrast, efficient single round transduction of monocytes is mediated by vectors derived from simian immunodeficiency virus of sooty mangabeys (SIVsmmPBj), depending on the presence of the viral accessory protein Vpx. Methods and Findings: Here we analyzed whether Vpx of SIVsmmPBj is sufficient for transduction of primary monocytes by HIV-1-derived vectors. To enable incorporation of PBj Vpx into HIV-1 vector particles, a HA-Vpr/Vpx fusion protein was generated. Supplementation of HIV-1 vector particles with this fusion protein was not sufficient to facilitate transduction of human monocytes. However, monocyte transduction with HIV-1-derived vectors was significantly enhanced after delivery of Vpx proteins by virus-like particles (VLPs) derived from SIVsmmPBj. Moreover, pre-incubation with Vpx-containing VLPs restored replication capacity of infectious HIV-1 in human monocytes. In monocytes of non-human primates, single-round transduction with HIV-1 vectors was enabled. Conclusion: Vpx enhances transduction of primary human and even non-human monocytes with HIV-1-derived vectors, only if delivered in the background of SIVsmmPBj-derived virus-like particles. Thus, for accurate Vpx function the presence of SIVsmmPBj capsid proteins might be required. Vpx is essential to overcome a block of early infection steps in primary monocytes
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