973 research outputs found

    CLIP-170/Tubulin-Curved Oligomers Coassemble at Microtubule Ends and Promote Rescues

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    AbstractBackground: CLIP-170 is a microtubule binding protein specifically located at microtubule plus ends, where it modulates their dynamic properties and their interactions with intracellular organelles. The mechanism by which CLIP-170 is targeted to microtubule ends remains unclear today, as well as its precise effect on microtubule dynamics.Results: We used the N-terminal part of CLIP-170 (named H2), which contains the microtubule binding domains, to investigate how it modulates in vitro microtubule dynamics and structure. We found that H2 primarily promoted rescues (transitions from shrinkage to growth) of microtubules nucleated from pure tubulin and isolated centrosomes, and stimulated microtubule nucleation. Electron cryomicroscopy revealed that H2 induced the formation of tubulin rings in solution and curved oligomers at the extremities of microtubules in assembly conditions.Conclusions: These results suggest that CLIP-170 targets specifically at microtubule plus ends by copolymerizing with tubulin and modulates microtubule nucleation, polymerization, and rescues by the same basic mechanism with tubulin oligomers as intermediates

    PAR7 MODELLING OF THE COST-EFFECTIVENESS OF RITUXIMAB FOR TREATMENT OF RHEUMATOID ARTHRITIS IN ITALY

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    Guidelines for choosing between multi-item and single-item scales for construct measurement: A predictive validity perspective

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    Establishing predictive validity of measures is a major concern in marketing research. This paper investigates the conditions favoring the use of single items versus multi-item scales in ter

    Risk factors for tuberculosis in dialysis patients: a prospective multi-center clinical trial

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    <p>Abstract</p> <p>Background</p> <p>Profound alterations in immune responses associated with uraemia and exacerbated by dialysis increase the risk of developing active tuberculosis (TB) in chronic haemodialysis patients (HDPs). In the current study, was determined the impact of various risk factors on TB development. Our aim was to identify which HDPs need anti-TB preventive therapy.</p> <p>Methods</p> <p>Prospective study of 272 HDPs admitted, through a 36-month period, to our institutions. Specific Relative Risk (RR) for TB was estimated, considering age matched subjects from the general population as reference group. Entering the study all patients were tested with tuberculin (TST). Using Cox's proportional hazard model the independent effect of various risk factors associated with TB development was estimated.</p> <p>Results</p> <p>History of TB, dialysis efficiency, use of Vitamin D supplements, serum albumin and zinc levels were not proved to influence significantly the risk for TB, in contrast to: advanced age (>65 years), BMI, diabetes mellitus, tuberculin reactivity, healed TB lesions on chest X-ray and time on dialysis. Elderly (>70 years old) HDPs (Adjusted RR 25.3, 95%CI 20.4-28.4, P < 0.02), diabetics (Adj.RR 25.3, 95%CI 17.2-21.1, P < 0.03), underweighted (Adj.RR 72.3, 95%CI 65.2-79.8 P < 0.001), tuberculin responders (Adj.RR 41.4, 95%CI 37.9-44.8, P < 0.03), HDPs with fibrotic lesions on chest x-ray (Adj.RR 82.3, 95%CI 51.3-95.5, P < 0.03) and those treated with haemodialysis for < 12 months (Adj.RR 110.0, 95%CI 97.4-135.3, P < 0.001), presented significantly higher specific RR for TB even after adjusting for the effect of the remaining studied risk factors.</p> <p>Conclusion</p> <p>The above mentioned factors have to be considered by the clinicians, evaluating for TB in HDPs. Positive TST, the existence of predisposing risk factors and/or old TB lesions on chest X-ray, will guide the diagnosis of latent TB infection and the selection of those HDPs who need preventive chemoprophylaxis.</p

    Quantifizierung von kapillarem Fluss, Filmfluss und Dampffluss durch inverse Simulation transienter Verdunstungsexperimente

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    Die Evaporation aus dem unbewachsenen Boden ist eine wichtige Komponente im Wasserhaushalt und der Energiebilanz der ErdoberflĂ€che, insbesondere in ariden und semiariden Gebieten mit geringer Vegetationsdichte. Die Modellierung des Wasserflusses in trockenen Böden und die Vorhersage von realer Evaporation und Grundwasserneubildung stellen eine stĂ€ndige Herausforderung fĂŒr die Bodenhydrologie dar und erfordern angemessene Modellkonzepte und Parametrisierungen der bodenhydraulischen Funktionen. WĂ€hrend die BerĂŒcksichtigung des Wasserdampftransports in trockenen porösen Medien inzwischen hĂ€ufig erfolgt, steckt die Parametrisierung der hydraulischen LeitfĂ€higkeitsfunktion im mittleren Wasserspannungsbereich noch immer in den Kinderschuhen und basiert in den meisten FĂ€llen weiterhin auf der Anwendung von KapillarbĂŒndelmodellen und wenigen DatensĂ€tzen aus der Literatur mit teilweise eingeschrĂ€nkter QualitĂ€t. Prozesse wie Film- und Eckenfluss wurden zwar an Hand einiger weniger DatensĂ€tze untersucht, werden jedoch in der Modellierung von Wasser- und EnergieflĂŒssen kaum berĂŒcksichtigt. In diesem Beitrag zeigen wir Daten aus transienten Verdunstungsversuchen an großen gepackten BodensĂ€ulen mit erweiterter Instrumentierung in den trockenen Bereich, die mit der Methode der inversen Modellierung prozessbasiert ausgewertet wurden. Es wird untersucht, welche Parametrisierung der hydraulischen LeitfĂ€higkeit zu einer korrekten Beschreibung der Zeitreihen der Wasserspannung fĂŒhrt. Die Analyse wird durch gekoppelte Simulationen des Wasser-, Dampf- und WĂ€rmetransports erweitert. Die Ergebnisse zeigen eindeutig das Scheitern klassischer Parametrisierungen der bodenhydraulischen Funktionen im mittleren und trockenen Bereich. Eine korrekte Beschreibung der Messdaten war nur durch Hinzunahme einer weiteren Komponente in der hydraulischen LeitfĂ€higkeitsfunktion möglich, deren physikalische Ursache wahrscheinlich der Film- und Eckenfluss ist

    Distributed, end-to-end verifiable, and privacy-preserving internet voting systems

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    We present the D-DEMOS suite of distributed, privacy-preserving, and end-to-end verifiable e-voting systems; one completely asynchronous and one with minimal timing assumptions but better performance. Their distributed voting operation is human verifiable; a voter can vote over the web, using an unsafe web client stack, without sacrificing her privacy, and get recorded-as-cast assurance. Additionally, a voter can outsource election auditing to third parties, still without sacrificing privacy. We provide a model and security analysis of the systems, implement prototypes of the complete systems, measure their performance experimentally, demonstrate their ability to handle large-scale elections, and demonstrate the performance trade-offs between the two versions

    Feasibility of tumour-focused adaptive radiotherapy for bladder cancer on the MR-linac.

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    Bladder tumour-focused magnetic resonance image-guided adaptive radiotherapy using a 1.5 Tesla MR-linac is feasible. A full online workflow adapting to anatomy at each fraction is achievable in approximately 30 min. Intra-fraction bladder filling did not compromise target coverage with the class solution employed

    Retrospective Assessment of Islet Cell Autoantibodies in Pancreas Organ Donors

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    OBJECTIVE—Of deceased pancreas donors, 3–4% may have autoantibodies (AAb) to pancreatic islet cell antigens; these autoantibodies are well-established markers of type 1 diabetes. We investigated whether donor AAb positivity could affect the outcome of pancreas transplantation

    Connecting the Edges: A Universal, Mobile-Centric, and Opportunistic Communications Architecture

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    The Internet has crossed new frontiers with access to it getting faster and cheaper. Considering that the architectural foundations of today's Internet were laid more than three decades ago, the Internet has done remarkably well until today coping with the growing demand. However, the future Internet architecture is expected to support not only the ever growing number of users and devices, but also a diverse set of new applications and services. Departing from the traditional host-centric access paradigm, where access to a desired content is mapped to its location, an information-centric model enables the association of access to a desired content with the content itself, irrespective of the location where it is being held. UMOBILE tailors the information-centric communication model to meet the requirements of opportunistic communications, integrating those connectivity approaches into a single architecture. By pushing services near the edge of the network, such an architecture can pervasively operate in any networking environment and allows for the development of innovative applications, providing access to data independent of the level of end-to-end connectivity availability
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