1,260 research outputs found

    Property Meeting the Challenge of the Commons

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    Sound generation by impulse excited plates coupled to acoustics cavities.

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    International audienceThis paper is concerned with vibroacoustics in the time domain. One of the aims is to compare results given by an semi-analytical technique based on the resonance modes with a finite difference technique. An other goal is to describe the response of a fluid-loaded plate (displacement of the structure and sound pressure in the fluid) coupled to a rigid cavity when it is excited by a Ricker wavelet and to see the influence of the excitation on the response of system

    Aeroacoustic source analysis in a corrugated flow pipe

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    International audienceThis study is focused on a phenomenon often encountered in flow carrying pipes, since flow instabilities caused by geometric features may generate acoustic signals and thereafter interact with these signals in such a way that powerful pure tones are produced. A modern example is found in the so-called " singing risers " , or the gas pipes connecting gas production platforms to the transport network. But the flow generated resonance in a fully corrugated circular pipe may be silenced by the addition of relatively low frequency flow oscillations induced by an acoustic generator. Experiments reported here, aimed at investigating in more detail the coupling between the flow in the pipe, the acoustically generated flow oscillations and the emitted resulting noise, are performed in a specifically designed facilit

    The October 1985 Long Outburst of U Geminorum: Revealing the Viscous Time Scale in Long Orbital Period Dwarf Novae

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    We examine the AAVSO light curve of U Geminorum from 1908 to 2002, with particular focus on the October 1985 outburst. This outburst was longer than any other seen in U Gem by about a factor of 2, and appears to be unique among all dwarf nova outbursts seen in systems with orbital periods longer than 3 hr in that one can measure the decay time scale during the initial slow decay. This rate is ~26+-6 d/mag. Using estimates of the rate of accretion during outburst taken from Froning et al., one can show that ~1e24 g of gas was accreted onto the white dwarf during the outburst. When coupled with the viscous time inferred from the (short orbital period) SU UMa stars, the U Gem viscous time scale lends support to the standard model in which the decays in dwarf novae can either be viscous or thermal, with the ratio between them being roughly h/r where h is the vertical pressure scale height in the disk.Comment: 11 pages, 3 figure

    Evaluation of a prostate cancer e-health-tutorial

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    Hintergrund: Angesichts verschiedener Behandlungsoptionen ist die Information und Therapieentscheidung beim lokalisierten Prostatakarzinom eine Herausforderung. Die digitale Informationstechnologie bietet im Vergleich zu gedruckten Informationen mehr Möglichkeiten, die Information und die Patientenkommunikation bedarfsgerecht zu gestalten. Ziele: Zur Unterstützung der Therapieentscheidung und der Kommunikation mit Patienten ist in der deutschsprachigen Schweiz ein Online-Tutorial in einem systematischen Prozess entwickelt und in einer Pilotstudie getestet worden. In der Evaluation interessierten die Nutzerzufriedenheit, die Erfüllung der Informationsbedürfnisse, die Vorbereitung auf die Therapieentscheidung und deren subjektive Qualität. Material und Methoden: Die Plattform wurde in einem iterativen Prozess mittels Fokusgruppen mit Ärzten und Patienten auf der Grundlage von Informationen aus bestehenden Broschüren entwickelt. Für den Test der Plattform wurden in 8 urologischen Kliniken 87 Patienten zur Teilnahme eingeladen. Die 56 Nutzer wurden 4 Wochen nach dem Login und 3 Monate nach dem Therapieentscheid online befragt, 48 Nutzer füllten beide Befragungen aus. Eingesetzte Instrumente waren die Preparation for Decision Making Scale (PDMS), die Decisional Conflict Scale (DCS) und die Decisional Regret Scale (DRS). Ergebnisse und Diskussion: Die Nutzenden sind mit der Plattform sehr zufrieden und finden ihre Informationsbedürfnisse gut erfüllt. Sie zeigen 3 Monate nach dem Entscheid eine gute Vorbereitung auf die Entscheidung (MW PDMS 75, SD 23) und berichten über niedrigen Entscheidungskonflikt (MW DCS 9.6, SD 11) und kaum Bedauern über die Entscheidung (MW DRS 6.4, SD 9.6). Basierend auf diesen Erkenntnissen kann die Plattform zur weiteren Nutzung empfohlen werden.Background: Due to the multitude of therapy options the treatment decision after diagnosis of a localised prostate cancer is challenging. Compared to printed booklets, web based information technology offers more possibilities to tailor information to patients’ individual needs. Objectives: To support the decision making process as well as the communication with patients we developed an online tutorial in a systematic process in the German speaking part of Switzerland and then tested it in a pilot study. The study investigated users’ satisfaction, the coverage of information needs, the preparation for decision making and the subjective quality of the decision. Materials and methods: Based on already existing information material the online tutorial was developed in an iterative process using focus groups with patients and urologists. For the following evaluation in eight clinics a total of 87 patients were invited to access the platform and participate in the study. From these patients 56 used the tutorial and 48 answered both surveys (the first one 4 weeks after the first login and the second one 3 months after treatment decision). The surveys used the Preparation for Decision Making Scale (PDMS), the Decisional Conflict Scale (DCS), and the Decisional Regret Scale (DRS). Results and Conclusion: Satisfaction with the tutorial is very high among patients with newly diagnosed localized prostate cancer. Users find their information needs sufficiently covered. Three months after the decision they felt that they were well prepared for the decision making (Mean PDMS 75, SD 23), they had low decisional conflict (Mean DCS 9.6, SD 11) and almost no decisional regret (Mean DRS 6.4, SD 9.6). Based on these findings the further use of the tutorial can be recommended

    Peripheral T-cell lymphoma unspecified (PTCL-U): a new prognostic model from a retrospective multicentric clinical study

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    To assess the prognosis of peripheral T-cell lymphoma unspecified, we retrospectively analyzed 385 cases fulfilling the criteria defined by the World Health Organization classification. Factors associated with a worse overall survival (OS) in a univariate analysis were age older than 60 years (P=.0002), equal to or more than 2 extranodal sites (P=.0002), lactic dehydrogenase (LDH) value at normal levels or above (P<.0001), performance status (PS) equal to or more than 2 (Pless than or equal to.0001), stage III or higher (P=.0001), and bone marrow involvement (P=.0001). Multivariate analysis showed that age (relative risk, 1.732; 95% CI, 1.300-2.309; P<.0001), PS (relative risk, 1.719; 95% CI, 1.269-2.327, P<.0001), LDH level (relative risk, 1.905; 95% CI, 1.415-2.564; P<.0001), and bone marrow involvement (relative risk, 1.454; 95% CI, 1.045-2.023; P=.026) were factors independently predictive for survival. Using these 4 variables we constructed a new prognostic model that singled out 4 groups at different risk: group 1, no adverse factors, with 5-year and 10-year OS of 62.3% and 54.9%, respectively; group 2, one factor, with a 5-year and 10-year OS of 52.9% and 38.8%, respectively; group 3, 2 factors, with 5-year and 10-year OS of 32.9% and 18.0%, respectively; group 4,3 or 4 factors, with a 5-year and 10-year OS of 18.3 and 12.6%, respectively (Pless than or equal to.0001; log-rank, 66.79)

    A CRISPR-Cas9-engineered mouse model for GPI anchor deficiency mirrors human phenotype and shows hippocampal synaptic dysfunctions

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    Pathogenic germline mutations in PIGV lead to glycosylphosphatidylinositol biosynthesis deficiency. Individuals with pathogenic biallelic mutations in genes of the glycosylphosphatidylinositol anchor pathway show cognitive impairments, a motor delay and in many cases epilepsy. Thus far, the pathophysiology underlying the disease remains unclear and suitable rodent models that mirror human pathophysiology have not been available. We therefore generated a mouse model using CRISPR-Cas9 to introduce the most prevalent hypomorphic missense mutation in European patients, at a site that is also conserved in mice, Pigv:c.1022C>A (p.A341E). Reflecting the human pathology mutant Pigv(341E) mice showed deficits in motor coordination and cognitive impairment with poorer long-term spatial memory than wild-type mice, as well as alterations in sociability and sleep patterns. Furthermore, immunohistochemistry showed decreased synaptophysin-immunoreactivity and electrophysiology recordings demonstrated reduced hippocampal synaptic transmission in Pigv(341E) mice that may underlie impaired memory formation. To gain a deeper and broader molecular understanding of the consequences of glycosylphosphatidylinositol anchor deficiency, we performed single-cell RNA sequencing on acutely isolated hippocampal cells of Pigv(341E) and wild-type mice. We found that hippocampal cells from adult Pigv(341E) mice exhibited changes in gene expression, most prominently in a subtype of microglia and subicular neurons. A significant reduction of Abl1 transcripts in several cell clusters suggests a link to the signaling pathway of glycosylphosphatidylinositol-anchored ephrins. We also observed increased levels of Hdc that might affect histamine metabolism with consequences in circadian rhythm. In summary, we present here the first mouse model with a patient-specific hypomorphic mutation that mirrors the human phenotype and shows a hippocampal synaptic defect. This new mouse model will not only open the doors for further investigation into the pathophysiology of glycosylphosphatidylinositol biosynthesis deficiency in future studies, but will also deepen our understanding in the role of glycosylphosphatidylinositol-anchor related pathways in brain development

    Analyses of circRNA expression throughout the light-dark cycle reveal a strong regulation of (Cdr1as), associated with light entrainment in the SCN

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    Circular RNAs (circRNAs) are a large class of relatively stable RNA molecules that are highly expressed in animal brains. Many circRNAs have been associated with CNS disorders accompanied by an aberrant wake-sleep cycle. However, the regulation of circRNAs in brain homeostasis over daily light-dark (LD) cycles has not been characterized. Here, we aim to quantify the daily expression changes of circRNAs in physiological conditions in healthy adult animals. Using newly generated and public RNA-Seq data, we monitored circRNA expression throughout the 12:12 h LD cycle in various mouse brain regions. We identified that (Cdr1as), a conserved circRNA that regulates synaptic transmission, is highly expressed in the suprachiasmatic nucleus (SCN), the master circadian pacemaker. Despite its high stability, (Cdr1as) has a very dynamic expression in the SCN throughout the LD cycle, as well as a significant regulation in the hippocampus following the entry into the dark phase. Computational integration of different public datasets predicted that (Cdr1as) is important for regulating light entrainment in the SCN. We hypothesize that the expression changes of (Cdr1as) in the SCN, particularly during the dark phase, are associated with light-induced phase shifts. Importantly, our work revises the current beliefs about natural circRNA stability and suggests that the time component must be considered when studying circRNA regulation

    Presymptomatic geographical distribution of ALS patients suggests the involvement of environmental factors in the disease pathogenesis

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    BackgroundGiven that the pathogenetic process of ALS begins many years prior to its clinical onset, examining patients' residential histories may offer insights on the disease risk factors. Here, we analyzed the spatial distribution of a large ALS cohort in the 50 years preceding the disease onset.MethodsData from the PARALS register were used. A spatial cluster analysis was performed at the time of disease onset and at 1-year intervals up to 50 years prior to that.ResultsA total of 1124 patients were included. The analysis revealed a higher-incidence cluster in a large area (435,000 inhabitants) west of Turin. From 9 to 2 years before their onset, 105 cases were expected and 150 were observed, resulting in a relative risk of 1.49 (P = 0.04). We also found a surprising high number of patients pairs (51) and trios (3) who lived in the same dwelling while not being related. Noticeably, these occurrences were not observed in large dwellings as we would have expected. The probability of this occurring in smaller buildings only by chance was very low (P = 0.01 and P = 0.04 for pairs and trios, respectively).ConclusionsWe identified a higher-incidence ALS cluster in the years preceding the disease onset. The cluster area being densely populated, many exposures could have contributed to the high incidence ALS cluster, while we could not find a shared exposure among the dwellings where multiple patients had lived. However, these findings support that exogenous factors are likely involved in the ALS pathogenesis
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