1,079 research outputs found

    A statistical model for application of maneuver flight loads data to structural design criteria

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    Statistical model for application of maneuver flight loads data to structural design dat

    Fatigue life estimates for helicopter loading spectra

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    Helicopter loading histories applied to notch metal samples are used as examples, and their fatigue lives are calculated by using a simplified version of the local strain approach. This simplified method has the advantage that it requires knowing the loading history in only the reduced form of ranges and means and number of cycles from the rain-flow cycle counting method. The calculated lives compare favorably with test data

    Hidden in Plain Sight: Subgroup Shifts Escape OOD Detection

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    The safe application of machine learning systems in healthcare relies on valid performance claims. Such claims are typically established in a clinical validation setting designed to be as close as possible to the intended use, but inadvertent domain or population shifts remain a fundamental problem. In particular, subgroups may be differently represented in the data distribution in the validation compared to the application setting. For example, algorithms trained on population cohort data spanning all age groups may be predominantly applied in elderly people. While these data are not “out-of distribution”, changes in the prevalence of different subgroups may have considerable impact on algorithm performance or will at least render original performance claims invalid. Both are serious problems for safely deploying machine learning systems. In this paper, we demonstrate the fundamental limitations of individual example out-of-distribution detection for such scenarios, and show that subgroup shifts can be detected on a population-level instead. We formulate population-level shift detection in the framework of statistical hypothesis testing and show that recent state-of-the-art statistical tests can be effectively applied to subgroup shift detection in a synthetic scenario as well as real histopathology images

    Formation and Recognition of UV-Induced DNA Damage within Genome Complexity

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    Ultraviolet (UV) light is a natural genotoxic agent leading to the formation of photolesions endangering the genomic integrity and thereby the survival of living organisms. To prevent the mutagenetic effect of UV, several specific DNA repair mechanisms are mobilized to accurately maintain genome integrity at photodamaged sites within the complexity of genome structures. However, a fundamental gap remains to be filled in the identification and characterization of factors at the nexus of UV-induced DNA damage, DNA repair, and epigenetics. This review brings together the impact of the epigenomic context on the susceptibility of genomic regions to form photodamage and focuses on the mechanisms of photolesions recognition through the different DNA repair pathways

    Das schilddrüsenähnliche follikuläre Nierenzellkarzinom

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    Das schilddrüsenähnliche follikuläre Nierenzellkarzinom wurde auf der Grundlage von bisher 9 Fallbeschreibungen als eigenständige Nierentumorentität postuliert. Diese neue Tumorentität ist bis dato nicht in der Tumorklassifikation der World Health Organisation (WHO) aufgeführt. Wir beschreiben hier einen weiteren Fall, der als Zufallsbefund bei der Autopsie eines 58-jährigen Patienten identifiziert wurde. Der Patient verstarb an den Folgen einer akuten myeloischen Leukämie nach Chemotherapie und hatte zusätzlich ein Adenokarzinom der Prostata. Der Nierentumor war im Nierenoberpol links lokalisiert und hatte einen Durchmesser von 3 cm bei grau-brauner Schnittfläche. Histologisch zeigte der Tumor das typische schilddrüsenähnliche mikro- und makrofollikuläre Bild sowie eosinophiles intrafollikuläres kolloidähnliches Material mit teils multifokalen Verkalkungsherden. Immunhistologisch war er CD10-positiv sowie TTF1- (thyroidaler Transkriptionsfaktor-1-) und Thyreoglobulin-negativ. Die Zusammenschau der publizierten Fälle zeigt, dass diese Tumoren ein geringes Metastasierungsrisiko besitzen. Die bisherigen Erfahrungen mit diesem Tumor sind allerdings zu gering, um das schilddrüsenähnliche follikuläre Nierenzellkarzinom als eigenständige Tumorentität für die nächste WHO-Klassifikation uneingeschränkt empfehlen zu können. = Thyroid-like follicular carcinoma of the kidney is postulated as a potentially new entity of renal tumor based on nine previously published case reports. This tumor entity is not yet integrated into the classification of tumors of the World Health Organization (WHO). In this article a new case of thyroid-like follicular carcinoma of kidney is described which was incidentally detected at autopsy. The 58-year-old patient died of complications of acute myeloid leukemia after chemotherapy and also had prostatic adenocarcinoma. The renal tumor in the left kidney had a diameter of 3 cm and showed a grey-brown cut surface. Histologically, the tumor presented with a typical thyroid-like microfollicular and macrofollicular structure filled with eosinophilic, colloid-like material with calcification. Immunohistologically the renal tumor was CD 10 positive and negative for thyroid transcription factor 1 (TTF1) and thyroglobulin. A synopsis of the published case reports indicates that thyroid-like follicular carcinoma of the kidney has a low risk of metastasis. More experience with further cases of thyroid-like follicular renal carcinoma is necessary before a recommendation of a separate tumor entity in the next WHO classification is justified

    Das schilddrüsenähnliche follikuläre Nierenzellkarzinom: Eine eigene Tumorentität?

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    Zusammenfassung: Das schilddrüsenähnliche follikuläre Nierenzellkarzinom wurde auf der Grundlage von bisher 9 Fallbeschreibungen als eigenständige Nierentumorentität postuliert. Diese neue Tumorentität ist bis dato nicht in der Tumorklassifikation der World Health Organisation (WHO) aufgeführt. Wir beschreiben hier einen weiteren Fall, der als Zufallsbefund bei der Autopsie eines 58-jährigen Patienten identifiziert wurde. Der Patient verstarb an den Folgen einer akuten myeloischen Leukämie nach Chemotherapie und hatte zusätzlich ein Adenokarzinom der Prostata. Der Nierentumor war im Nierenoberpol links lokalisiert und hatte einen Durchmesser von 3cm bei grau-brauner Schnittfläche. Histologisch zeigte der Tumor das typische schilddrüsenähnliche mikro- und makrofollikuläre Bild sowie eosinophiles intrafollikuläres kolloidähnliches Material mit teils multifokalen Verkalkungsherden. Immunhistologisch war er CD10-positiv sowie TTF1- (thyroidaler Transkriptionsfaktor-1-) und Thyreoglobulin-negativ. Die Zusammenschau der publizierten Fälle zeigt, dass diese Tumoren ein geringes Metastasierungsrisiko besitzen. Die bisherigen Erfahrungen mit diesem Tumor sind allerdings zu gering, um das schilddrüsenähnliche follikuläre Nierenzellkarzinom als eigenständige Tumorentität für die nächste WHO-Klassifikation uneingeschränkt empfehlen zu können

    Retinal horizontal cells use different synaptic sites for global feedforward and local feedback signaling

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    In the outer plexiform layer (OPL) of the mouse retina, two types of cone photoreceptors (cones) provide input to more than a dozen types of cone bipolar cells (CBCs). This transmission is modulated by a single horizontal cell (HC) type, the only interneuron in the outer retina. Horizontal cells form feedback synapses with cones and feedforward synapses with CBCs. However, the exact computational role of HCs is still debated. Along with performing global signaling within their laterally coupled network, HCs also provide local, cone-specific feedback. Specifically, it has not been clear which synaptic structures HCs use to provide local feedback to cones and global forward signaling to CBCs. Here, we reconstructed in a serial block-face electron microscopy volume the dendritic trees of five HCs as well as cone axon terminals and CBC dendrites to quantitatively analyze their connectivity. In addition to the fine HC dendritic tips invaginating cone axon terminals, we also identified “bulbs”, short segments of increased dendritic diameter on the primary dendrites of HCs. These bulbs are located well below the cone axon terminal base and make contact to other cells mostly identified as other HCs or CBCs. Using immunolabeling we show that HC bulbs express vesicular gamma-aminobutyric acid transporters and co-localize with GABA receptor γ2 subunits. Together, this suggests the existence of two synaptic strata in the mouse OPL, spatially separating cone-specific feedback and feedforward signaling to CBCs. A biophysics-based computational model of a HC dendritic branch supports the hypothesis that the spatial arrangement of synaptic contacts allows simultaneous local feedback and global feedforward signaling

    The Glass Transition Temperature of Water: A Simulation Study

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    We report a computer simulation study of the glass transition for water. To mimic the difference between standard and hyperquenched glass, we generate glassy configurations with different cooling rates and calculate the TT dependence of the specific heat on heating. The absence of crystallization phenomena allows us, for properly annealed samples, to detect in the specific heat the simultaneous presence of a weak pre-peak (``shadow transition''), and an intense glass transition peak at higher temperature. We discuss the implications for the currently debated value of the glass transition temperature of water. We also compare our simulation results with the Tool-Narayanaswamy-Moynihan phenomenological model.Comment: submitted to Phys. Re

    Elastin is Localised to the Interfascicular Matrix of Energy Storing Tendons and Becomes Increasingly Disorganised With Ageing

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    Tendon is composed of fascicles bound together by the interfascicular matrix (IFM). Energy storing tendons are more elastic and extensible than positional tendons; behaviour provided by specialisation of the IFM to enable repeated interfascicular sliding and recoil. With ageing, the IFM becomes stiffer and less fatigue resistant, potentially explaining why older tendons become more injury-prone. Recent data indicates enrichment of elastin within the IFM, but this has yet to be quantified. We hypothesised that elastin is more prevalent in energy storing than positional tendons, and is mainly localised to the IFM. Further, we hypothesised that elastin becomes disorganised and fragmented, and decreases in amount with ageing, especially in energy storing tendons. Biochemical analyses and immunohistochemical techniques were used to determine elastin content and organisation, in young and old equine energy storing and positional tendons. Supporting the hypothesis, elastin localises to the IFM of energy storing tendons, reducing in quantity and becoming more disorganised with ageing. These changes may contribute to the increased injury risk in aged energy storing tendons. Full understanding of the processes leading to loss of elastin and its disorganisation with ageing may aid in the development of treatments to prevent age related tendinopathy

    Does the maturation of early sleep patterns predict language ability at school entry? : A Born in Bradford study

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    Children's vocabulary ability at school entry is highly variable and predictive of later language and literacy outcomes. Sleep is potentially useful in understanding and explaining that variability, with sleep patterns being predictive of global trajectories of language acquisition. Here, we looked to replicate and extend these findings. Data from 354 children (without English as an additional language) in the Born in Bradford study were analysed, describing the mean intercepts and linear trends in parent-reported day-time and night-time sleep duration over five time points between 6 and 36 months-of-age. The mean difference between night-time and day-time sleep was predictive of receptive vocabulary at age five, with more night-time sleep relative to day-time sleep predicting better language. An exploratory analysis suggested that socioeconomic status was predictive of vocabulary outcomes, with sleep patterns partially mediating this relationship. We suggest that the consolidation of sleep patterns acts as a driver of early language development
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