1,343 research outputs found

    Fibroblasts in head neck squamous cell carcinoma associated with perineural invasion have high level nuclear Yes-Associated Protein (YAP) expression

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    Paul A. Reynolds, PhD, is supported by the Melville Trust for the Care and cure of Cancer.We retrospectively studied the expression of Yes-associated protein (YAP) using immunohistochemical staining in 10 cases of head and neck squamous cell carcinoma with associated perineural invasion. We find that fibroblasts in areas associated with perineural invasion show higher levels of nuclear YAP compared to fibroblasts in the stroma of normal mucosa, with a median cell count of 35.4 per high-power field in the former and 3.9 in the latter. No differences were observed between the expression of YAP phosphorylated at Ser127 in the tumoral stroma compared to that in the normal mucosa, with a median cell count expression of 4.9 in the former versus 5.0 in the latter. Therefore, a strong and increased nuclear YAP expression in fibroblasts associated with perineural invasion in head and neck squamous cell carcinoma suggests that YAP-mediated transcription programs in these fibroblasts may contribute to perineural invasion.PostprintPublisher PDFPeer reviewe

    Stochastic urban pluvial flood hazard maps based upon a spatial-temporal rainfall generator

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    It is a common practice to assign the return period of a given storm event to the urban pluvial flood event that such storm generates. However, this approach may be inappropriate as rainfall events with the same return period can produce different urban pluvial flooding events, i.e., with different associated flood extent, water levels and return periods. This depends on the characteristics of the rainfall events, such as spatial variability, and on other characteristics of the sewer system and the catchment. To address this, the paper presents an innovative contribution to produce stochastic urban pluvial flood hazard maps. A stochastic rainfall generator for urban-scale applications was employed to generate an ensemble of spatially—and temporally—variable design storms with similar return period. These were used as input to the urban drainage model of a pilot urban catchment (~9 km2) located in London, UK. Stochastic flood hazard maps were generated through a frequency analysis of the flooding generated by the various storm events. The stochastic flood hazard maps obtained show that rainfall spatial-temporal variability is an important factor in the estimation of flood likelihood in urban areas. Moreover, as compared to the flood hazard maps obtained by using a single spatially-uniform storm event, the stochastic maps generated in this study provide a more comprehensive assessment of flood hazard which enables better informed flood risk management decisions

    Rapid Dynamics of Contrast Responses in the Cat Primary Visual Cortex

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    The visual information we receive during natural vision changes rapidly and continuously. The visual system must adapt to the spatiotemporal contents of the environment in order to efficiently process the dynamic signals. However, neuronal responses to luminance contrast are usually measured using drifting or stationary gratings presented for a prolonged duration. Since motion in our visual field is continuous, the signals received by the visual system contain an abundance of transient components in the contrast domain. Here using a modified reverse correlation method, we studied the properties of responses of neurons in the cat primary visual cortex to different contrasts of grating stimuli presented statically and transiently for 40 ms, and showed that neurons can effectively discriminate the rapidly changing contrasts. The change in the contrast response function (CRF) over time mainly consisted of an increment in contrast gain (CRF shifts to left) in the developing phase of temporal responses and a decrement in response gain (CRF shifts downward) in the decay phase. When the distribution range of stimulus contrasts was increased, neurons demonstrated decrement in contrast gain and response gain. Our results suggest that contrast gain control (contrast adaptation) and response gain control mechanisms are well established during the first tens of milliseconds after stimulus onset and may cooperatively mediate the rapid dynamic responses of visual cortical neurons to the continuously changing contrast. This fast contrast adaptation may play a role in detecting contrast contours in the context of visual scenes that are varying rapidly

    Finite-time reliable nonfragile control for fractionalorder nonlinear systems with asymmetrical saturation and structured uncertainties

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    This paper investigates the finite-time stabilization problem of fractional-order nonlinear differential systems via an asymmetrically saturated reliable control in the sense of Caputo’s fractional derivative. In particular, an asymmetrical saturation control problem is converted to a symmetrical saturation control problem by using a linear matrix inequality framework criterion to achieve the essential results. Specifically, in this paper, we obtain two sets of sufficient conditions under different scenarios of structured uncertainty, namely, norm-bounded parametric uncertainty and linear fractional transformation uncertainty. The uncertainty considered in this paper is a combination of polytopic form and structured form. With the help of control theories of fractional-order system and linear matrix inequality technique, some sufficient criteria to ensure reliable finite-time stability of fractional-order differential systems by using the indirect Lyapunov approach are derived. As a final point, the derived criteria are numerically validated by means of examples based on financial fractional-order differential system and permanent magnet synchronous motor chaotic fractional-order differential system

    Structural biology of calcium phosphate nanoclusters sequestered by phosphoproteins

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    Biofluids that contain stable calcium phosphate nanoclusters sequestered by phosphopeptides make it possible for soft and hard tissues to co-exist in the same organism with relative ease. The stability diagram of a solution of nanocluster complexes shows how the minimum concentration of phosphopeptide needed for stability increases with pH. In the stable region, amorphous calcium phosphate cannot precipitate. Nevertheless, if the solution is brought into contact with hydroxyapatite, the crystalline phase will grow at the expense of the nanocluster complexes. The physico-chemical principles governing the formation, composition, size, structure, and stability of the complexes are described. Examples are given of complexes formed by casein, osteopontin, and recombinant phosphopeptides. Application of these principles and properties to blood serum, milk, urine, and resting saliva is described to show that under physiological conditions they are in the stable region of their stability diagram and so cannot cause soft tissue calcification. Stimulated saliva, however, is in the metastable region, consistent with its role in tooth remineralization. Destabilization of biofluids, with consequential ill-effects, can occur when there is a failure of homeostasis, such as an increase in pH without a balancing increase in the concentration of sequestering phosphopeptides

    Genetic Pharmacotherapy

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    Bi-objective optimization for low-carbon product family design

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    [EN] Consumers, industry, and government entities are becoming increasingly concerned about the issue of global warming. With this in mind, manufacturers have begun to develop products with consideration of low-carbon. In recent years, many companies are utilizing product families to satisfy various customer needs with lower costs. However, little research has been conducted on the development of a product family that considers environmental factors. In this paper, a low-carbon product family design that integrates environmental concerns is proposed. To this end, a new method of platform planning is investigated with considerations of cost and greenhouse gas (GHG) emission of a product family simultaneously. In this research, a lowcarbon product family design problem is described at first, and then a GHG emission model of product family is established. Furthermore, to support lowcarbon product family design, an optimization method is applied to make a significant trade-off between cost and GHG emission to implement a feasible platform planning. Finally, the effectiveness of the proposed method is illustrated through a case study. (C) 2016 Elsevier Ltd. All rights reserved.This research was carried out as a part of the CASES project which is supported by a Marie Curie International Research Staff Exchange Scheme Fellowship within the 7th European Community Framework Programme under the Grant agreement no. 294931. This research was also supported by National Natural Science Foundation of China (Nos. 51175262, 51575264); and Jiangsu Province Science Foundation for Excellent Youths under Grant BK2012032.Wang, Q.; Dunbing, T.; Yin, L.; Salido, MA.; Giret Boggino, AS.; Xu, Y. (2016). Bi-objective optimization for low-carbon product family design. Robotics and Computer-Integrated Manufacturing. 41:53-65. https://doi.org/10.1016/j.rcim.2016.02.001S53654

    Change in neighborhood socioeconomic status and childhood weight status and body composition from birth to adolescence

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    Background: We aim to assess the associations between the change in neighborhood socioeconomic score (SES) between birth and 6 years and childhood weight status and body composition from 6 to 13 years.Methods: Data for 3909 children from the Generation R Study, a prospective population-based cohort in the Netherlands were analyzed. The change in neighborhood SES between birth and 6 years was defined as static-high, static-middle, static-low, upward, and downward mobility. Child body mass index (BMI), overweight and obesity (OWOB), fat mass index (FMI) and lean mass index (LMI) were measured at age 6, 10, and 13 years. The associations were explored using generalized estimating equations. The effect modification by child sex was examined. Results: In total, 19.5% and 18.1% of children were allocated to the upward mobility and downward mobility neighborhood SES group. The associations between the change in neighborhood SES and child weight status and body composition were moderated by child sex (p &lt; 0.05). Compared to girls in the static-high group, girls in the static-low group had relatively higher BMI-SDS (β, 95% confidence interval (CI): 0.24, 0.09–0.40) and higher risk of OWOB (RR, 95% CI: 1.98, 1.35–2.91), together with higher FMI-SDS (β, 95% CI: 0.27, 0.14–0.41) and LMI-SDS (β, 95% CI: 0.18, 0.03–0.33). The associations in boys were not significant. Conclusions: An increased BMI and fat mass, and higher risk of OWOB from 6 to 13 years were evident in girls living in a low-SES neighborhood or moving downward from a high- to a low-SES neighborhood. Support for children and families from low-SES neighborhoods is warranted.</p
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