713 research outputs found

    Trakhtenbrot's Theorem in Coq, A Constructive Approach to Finite Model Theory

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    We study finite first-order satisfiability (FSAT) in the constructive setting of dependent type theory. Employing synthetic accounts of enumerability and decidability, we give a full classification of FSAT depending on the first-order signature of non-logical symbols. On the one hand, our development focuses on Trakhtenbrot's theorem, stating that FSAT is undecidable as soon as the signature contains an at least binary relation symbol. Our proof proceeds by a many-one reduction chain starting from the Post correspondence problem. On the other hand, we establish the decidability of FSAT for monadic first-order logic, i.e. where the signature only contains at most unary function and relation symbols, as well as the enumerability of FSAT for arbitrary enumerable signatures. All our results are mechanised in the framework of a growing Coq library of synthetic undecidability proofs

    The importance of sleep: attentional problems in school-aged children with Down syndrome and Williams syndrome

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    Authors: Anna Ashworth ; Catherine M. Hill ; Annette Karmiloff-Smith ; Dagmara Dimitriou Article URL: http://www.tandfonline.com/doi/full/10.1080/15402002.2014.940107?ai=2gs&mi=3h6sxt&af=R Citation: Behavioral Sleep Medicine Publication Date: Fri, 15 Aug 2014 14:22:59 GM

    Processing-Induced Disorder in Pharmaceutical Materials

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    This chapter focuses on the major types of pharmaceutical processing methods that have been widely reported to produce disordered material either intentionally or unintentionally. Milling is one of the most frequently used unit operations used by the pharmaceutical industry for reducing the particle size of solids. Thermal processing techniques are mainly used for controlling or improving the release and the subsequent bioavailability of an active pharmaceutical ingredient (API). Techniques such as melt-mixing, spray-congealing, sintering, melt-granulation, and hot-melt extrusion (HME) have developed and evolved rapidly for large-scale pharmaceutical production. Solvent-evaporation-based methods are important processing techniques for both raw materials, such as crystallization of the raw drug, and formulation manufacturing in the pharmaceutical industry. The chapter discusses the processing that can potentially induce the formation of the disordered state during the manufacture of formulations. The widely used solvent-evaporation-based processing techniques in pharmaceutical formulation production include spray-drying, freeze-drying, film casting, and film coating

    Incompressible Fluids of the de Sitter Horizon and Beyond

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    There are (at least) two surfaces of particular interest in eternal de Sitter space. One is the timelike hypersurface constituting the lab wall of a static patch observer and the other is the future boundary of global de Sitter space. We study both linear and non-linear deformations of four-dimensional de Sitter space which obey the Einstein equation. Our deformations leave the induced conformal metric and trace of the extrinsic curvature unchanged for a fixed hypersurface. This hypersurface is either timelike within the static patch or spacelike in the future diamond. We require the deformations to be regular at the future horizon of the static patch observer. For linearized perturbations in the future diamond, this corresponds to imposing incoming flux solely from the future horizon of a single static patch observer. When the slices are arbitrarily close to the cosmological horizon, the finite deformations are characterized by solutions to the incompressible Navier-Stokes equation for both spacelike and timelike hypersurfaces. We then study, at the level of linearized gravity, the change in the discrete dispersion relation as we push the timelike hypersurface toward the worldline of the static patch. Finally, we study the spectrum of linearized solutions as the spacelike slices are pushed to future infinity and relate our calculations to analogous ones in the context of massless topological black holes in AdS4_4.Comment: 27 pages, 8 figure

    Local induction of lymphangiogenesis with engineered fibrin-binding VEGF-C promotes wound healing by increasing immune cell trafficking and matrix remodeling

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    Lymphangiogenesis occurs in inflammation and wound healing, yet its functional roles in these processes are not fully understood. Consequently, clinically relevant strategies for therapeutic lymphangiogenesis remain underdeveloped, particularly using growth factors. To achieve controlled, local capillary lymphangiogenesis with protein engineering and determine its effects on fluid clearance, leukocyte trafficking, and wound healing, we developed a fibrin-binding variant of vascular endothelial growth factor C (FB-VEGF-C) that is slowly released upon demand from infiltrating cells. Using a novel wound healing model, we show that implanted fibrin containing FB-VEGF-C, but not free VEGF-C, could stimulate local lymphangiogenesis in a dose-dependent manner. Importantly, the effects of FB-VEGF-C were restricted to lymphatic capillaries, with no apparent changes to blood vessels and downstream collecting vessels. Leukocyte intravasation and trafficking to lymph nodes were increased in hyperplastic lymphatics, while fluid clearance was maintained at physiological levels. In diabetic wounds, FB-VEGF-C-induced lymphangiogenesis increased extracellular matrix deposition and granulation tissue thickening, indicators of improved wound healing. Together, these results indicate that FB-VEGF-C is a promising strategy for inducing lymphangiogenesis locally, and that such lymphangiogenesis can promote wound healing by enhancing leukocyte trafficking without affecting downstream lymphatic collecting vessels. (C) 2017 The Authors. Published by Elsevier Ltd

    A three-dimensional atlas of human dermal leukocytes, lymphatics, and blood vessels.

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    Dendritic cells (DCs), macrophages (Mφ), and T cells are major components of the skin immune system, but their interstitial spatial organization is poorly characterized. Using four-channel whole-mount immunofluorescence staining of the human dermis, we demonstrated the three-dimensional distribution of CD31(+) blood capillaries, LYVE-1(+) lymphatics, discrete populations of CD11c(+) myeloid DCs, FXIIIa(+) Mφ, and lymphocytes. We showed phenotypic and morphological differences in situ between DCs and Mφ. DCs formed the first dermal cellular layer (0-20 μm beneath the dermoepidermal junction), Mφ were located deeper (40-60 μm), and CD3(+) lymphocytes were observed throughout (0-60 μm). Below this level, DCs, T cells, and the majority of Mφ formed stable perivascular sheaths. Whole-mount imaging revealed the true extent of dermal leukocytes previously underestimated from cross-section views. The total area of apical dermis (0-30 μm) contained approximately 10-fold more myeloid DCs than the entire blood volume of an average individual. Surprisingly, <1% of dermal DCs occupied lymphatics in freshly isolated skin. Dermal DCs rapidly accumulated within lymphatics, but Mφ remained fixed in skin explants cultured ex vivo. The leukocyte architecture observed in normal skin was distorted in inflammation and disease. These studies illustrate the micro-anatomy of dermal leukocytes and provide further insights into their functional organization

    Public awareness and healthcare professional advice for obesity as a risk factor for cancer in the UK:a cross-sectional survey

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    BACKGROUND: Overweight and obesity is the second biggest preventable cause of cancer after smoking, causing ~3.4 million deaths worldwide. This study provides current UK data on awareness of the link between obesity and cancer by socio-demographic factors, including BMI, and explores to what degree healthcare professionals provide weight management advice to patients. METHODS: Cross-sectional survey of 3293 adults completed an online survey in February/March 2016, weighted to be representative of the UK population aged 18+. RESULTS: Public awareness of the link between obesity and cancer is low (25.4% unprompted and 57.5% prompted). Higher levels of awareness existed for least deprived groups (P < 0.001), compared to more deprived groups. Most respondents had seen a healthcare practitioner in the past 12 months (91.6%) and 17.4% had received advice about their weight, although 48.4% of the sample were overweight/obese. CONCLUSION: Cancer is not at the forefront of people’s minds when considering health conditions associated with overweight or obesity. Socio-economic disparities exist in health knowledge across the UK population, with adults from more affluent groups being most aware. Healthcare professionals are uniquely positioned to provide advice about weight, but opportunities for intervention are currently under-utilized in healthcare settings

    Running away experience and psychoactive substance use among adolescents in Taiwan: multi-city street outreach survey

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    <p>Abstract</p> <p>Background</p> <p>This study aimed to examine: 1) the relationship between being a runaway and the time since the first absconding event and adolescent substance use; 2) whether different kinds of psychoactive substances have a different temporal relationship to the first absconding event; and 3) whether the various reasons for the first absconding event are associated with different risks of substance use.</p> <p>Methods</p> <p>Participants were drawn from the 2004-2006 nationwide outreach programs across 26 cities/towns in Taiwan. A total of 17,133 participants, age 12-18 years, who completed an anonymous questionnaire on their experience of running away and substances use and who were now living with their families, were included in the analysis.</p> <p>Results</p> <p>The lifetime risk of tobacco, alcohol, betel nut, and illegal drug/inhalant use increased steadily from adolescents who had experienced a trial runaway episode (one time lasting ≤ 1 day), to those with extended runaway experience (≥ 2 times or lasting > 1 day), when compared to those who had never ran away. Adolescents who had their first running away experience > 6 months previously had a greater risk of betel nut or illegal drug/inhalant use over the past 6-months than those with a similar experience within the last 6 months. Both alcohol and tobacco use were most frequently initiated before the first running away, whereas both betel nut and illegal drug/inhalant use were most frequently initiated after this event. When adolescents who were fleeing an unsatisfactory home life were compared to those who ran away for excitement, the risk of alcohol use was similar but the former tended to have a higher risk of tobacco, betel nut, and illegal drug/inhalant use.</p> <p>Conclusions</p> <p>More significant running away and a longer time since the first absconding experience were associated with more advanced substance involvement among adolescents now living in a family setting. Once adolescents had left home, they developed additional psychoactive substance problems, regardless of their reasons for running away. These findings have implications for caregivers, teachers, and healthcare workers when trying to prevent and/or intervening in adolescent substance use.</p
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