381 research outputs found

    Theory of first-order layering transitions in thin helium films

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    Journals published by the American Physical Society can be found at http://journals.aps.org/Thin liquid He-4 films on graphite show evidence of layered growth with increasing number density via a succession of first-order phase transitions. These so-called ''layering transitions'' separate uniformly covering phases, such as monolayers and bilayers. The present work is a detailed theoretical study of such layering transitions using a Maxwell construction. We model the graphite surface by a strong substrate potential, and using a microscopic variational theory we obtain the uniform coverage solutions for liquid helium. For each layer, the theory yields the chemical potential mu and surface tension alpha as functions of coverage n, and from this we deduce mu(a). For each set of adjacent layers, we then obtain the crossing point in the curves of mu(alpha). In this way we obtain the values of mu, alpha, and surface coverages for the transition. Particular attention is paid to the monolayer-bilayer transition

    The molecular function of kallikrein-related peptidase 14 demonstrates a key modulatory role in advanced prostate cancer

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    Kallikrein-related peptidase 14 (KLK14) is one of several secreted KLK serine proteases involved in prostate cancer (PCa) pathogenesis. While relatively understudied, recent reports have identified KLK14 as overexpressed during PCa development. However, the modulation of KLK14 expression during PCa progression and the molecular and biological functions of this protease in the prostate tumour microenvironment remain unknown. To determine the modulation of KLK14 expression during PCa progression, we analysed the expression levels of KLK14 in patient samples using publicly available databases and immunohistochemistry. In order to delineate the molecular mechanisms involving KLK14 in PCa progression, we integrated proteomic, transcriptomic and in vitro assays with the goal to identify substrates, related-signalling pathways and functional roles of this protease. We showed that KLK14 expression is elevated in advanced PCa, and particularly in metastasis. Additionally, KLK14 levels were found to be decreased in PCa tissues from patients responsive to neo-adjuvant therapy compared to untreated patients. Furthermore, we also identified that KLK14 expression re-occurred in patients who developed castrate-resistant PCa. The combination of proteomic and transcriptomic analysis as well as functional assays revealed several new KLK14-substrates (agrin, desmoglein 2, vitronectin, laminins) and KLK14-regulated genes (Interleukin 32, midkine, Sox9), particularly an involvement of the MAPK1 and IL1RN pathways, and an involvement of KLK14 in the regulation of cellular migration, supporting its involvement in aggressive features of PCa progression. In conclusion, our work showed that KLK14 expression is associated with the development of aggressive PCa suggesting that targeting this protease could offer a novel route to limit the progression of prostate tumours. Additional work is necessary to determine the benefits and implications of targeting/co-targeting KLK14 in PCa as well as to determine the potential use of KLK14 expression as a predictor of PCa aggressiveness or response to treatment

    Inside the guts of wood-eating catfishes: can they digest wood?

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    To better understand the structure and function of the gastrointestinal (GI) tracts of wood-eating catfishes, the gross morphology, length, and microvilli surface area (MVSA) of the intestines of wild-caught Panaque nocturnus, P. cf. nigrolineatus “Marañon”, and Hypostomus pyrineusi were measured, and contrasted against these same metrics of a closely related detritivore, Pterygoplichthys disjunctivus. All four species had anatomically unspecialized intestines with no kinks, valves, or ceca of any kind. The wood-eating catfishes had body size-corrected intestinal lengths that were 35% shorter than the detritivore. The MVSA of all four species decreased distally in the intestine, indicating that nutrient absorption preferentially takes place in the proximal and mid-intestine, consistent with digestive enzyme activity and luminal carbohydrate profiles for these same species. Wild-caught Pt. disjunctivus, and P. nigrolineatus obtained via the aquarium trade, poorly digested wood cellulose (<33% digestibility) in laboratory feeding trials, lost weight when consuming wood, and passed stained wood through their digestive tracts in less than 4 h. Furthermore, no selective retention of small particles was observed in either species in any region of the gut. Collectively, these results corroborate digestive enzyme activity profiles and gastrointestinal fermentation levels in the fishes’ GI tracts, suggesting that the wood-eating catfishes are not true xylivores such as beavers and termites, but rather, are detritivores like so many other fishes from the family Loricariidae

    Demography and disorders of German Shepherd Dogs under primary veterinarycare in the UK

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    The German Shepherd Dog (GSD) has been widely used for a variety of working roles. However, concerns for the health and welfare of the GSD have been widely aired and there is evidence that breed numbers are now in decline in the UK. Accurate demographic and disorder data could assist with breeding and clinical prioritisation. The VetCompassTM Programme collects clinical data on dogs under primary veterinary care in the UK. This study included all VetCompassTM dogs under veterinary care during 2013. Demographic, mortality and clinical diagnosis data on GSDs were extracted and reported

    Do herbivorous minnows have “plug-flow reactor” guts? Evidence from digestive enzyme activities, gastrointestinal fermentation, and luminal nutrient concentrations

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    Few investigations have empirically analyzed fish gut function in the context of chemical reactor models. In this study, digestive enzyme activities, levels of gastrointestinal fermentation products [short chain fatty acids (SCFA)], luminal nutrient concentrations, and the mass of gut contents were measured along the digestive tract in herbivorous and carnivorous minnows to ascertain whether their guts function as “plug-flow reactors” (PFRs). Four of the species, Campostoma anomalum, C. ornatum, C. oligolepis, and C. pauciradii, are members of a monophyletic herbivorous clade, whereas the fifth species, Nocomis micropogon, is a carnivore from an adjacent carnivorous clade. In the context of a PFR model, the activities of amylase, trypsin and lipase, and the concentrations of glucose, protein, and lipid were predicted to decrease moving from the proximal to the distal intestine. I found support for this as these enzyme activities and nutrient concentrations generally decreased moving distally along the intestine of the four Campostoma species. Furthermore, gut content mass and the low SCFA concentrations did not change (increase or decrease) along the gut of any species. Combined with a previous investigation suggesting that species of Campostoma have rapid gut throughput rates, the data presented here generally support Campostoma as having guts that function as PFRs. The carnivorous N. micropogon showed some differences in the measured parameters, which were interpreted in the contexts of intake and retention time to suggest that PFR function breaks down in this carnivorous species

    A Genetics-First Approach to Dissecting the Heterogeneity of Autism: Phenotypic Comparison of Autism Risk Copy Number Variants

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    OBJECTIVE: Certain copy number variants (CNVs) greatly increase the risk of autism. The authors conducted a genetics-first study to investigate whether heterogeneity in the clinical presentation of autism is underpinned by specific genotype-phenotype relationships. METHODS: This international study included 547 individuals (mean age, 12.3 years [SD=4.2], 54% male) who were ascertained on the basis of having a genetic diagnosis of a rare CNV associated with high risk of autism (82 16p11.2 deletion carriers, 50 16p11.2 duplication carriers, 370 22q11.2 deletion carriers, and 45 22q11.2 duplication carriers), as well as 2,027 individuals (mean age, 9.1 years [SD=4.9], 86% male) with autism of heterogeneous etiology. Assessments included the Autism Diagnostic Interview-Revised and IQ testing. RESULTS: The four genetic variant groups differed in autism symptom severity, autism subdomain profile, and IQ profile. However, substantial variability was observed in phenotypic outcome in individual genetic variant groups (74%-97% of the variance, depending on the trait), whereas variability between groups was low (1%-21%, depending on the trait). CNV carriers who met autism criteria were compared with individuals with heterogeneous autism, and a range of profile differences were identified. When clinical cutoff scores were applied, 54% of individuals with one of the four CNVs who did not meet full autism diagnostic criteria had elevated levels of autistic traits. CONCLUSIONS: Many CNV carriers do not meet full diagnostic criteria for autism but nevertheless meet clinical cutoffs for autistic traits. Although profile differences between variants were observed, there is considerable variability in clinical symptoms in the same variant

    Bone pain and extremely low bone mineral density due to severe vitamin D deficiency in celiac disease

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    Case report A 29-year-old wheelchair-bound woman was presented to us by the gastroenterologist with suspected osteomalacia. She had lived in the Netherlands all her life and was born of Moroccan parents. Her medical history revealed iron deficiency, growth retardation, and celiac disease, for which she was put on a gluten-free diet. She had progressive bone pain since 2 years, difficulty with walking, and about 15 kg weight loss. She had a short stature, scoliosis, and pronounced kyphosis of the spine and poor condition of her teeth. Laboratory results showed hypocalcemia, an immeasurable serum25-hydroxyvitamin D level, and elevated parathyroid hormone and alkaline phosphatase levels. Spinal radiographs showed unsharp, low contrast vertebrae. Bone mineral density measurement at the lumbar spine and hip showed a T-score of -6.0 and -6.5, respectively. A bone scintigraphy showed multiple hotspots in ribs, sternum, mandible, and long bones. A duodenal biopsy revealed villous atrophy (Marsh 3C) and positive antibodies against endomysium, transglutaminase, and gliadin, compatible with active celiac disease. A bone biopsy showed severe osteomalacia but normal bone volume. She was treated with calcium intravenously and later orally. Furthermore, she was treated with high oral doses of vitamin D and a gluten-free diet. After a few weeks of treatment, her bone pain decreased, and her muscle strength improved. Discussion In this article, the pathophysiology and occurrence of osteomalacia as a complication of celiac disease are discussed. Low bone mineral density can point to osteomalacia as well as osteoporosis. © International Osteoporosis Foundation and National Osteoporosis Foundation 2011

    Early Geometrical Thinking in the Environment of Patterns, Mosaics and Isometries

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    This book discusses the learning and teaching of geometry, with a special focus on kindergarten and primary education. It examines important new trends and developments in research and practice, and emphasizes theoretical, empirical and developmental issues. Further, it discusses various topics, including curriculum studies and implementation, spatial abilities and geometric reasoning, as well as the psychological roots of geometrical thinking and teacher preparation in geometry education. It considers these issues from historical, epistemological, cognitive semiotic and educational points of view in the context of students' difficulties and the design of teaching and curricula

    Modelling the Costs and Effects of Selective and Universal Hospital Admission Screening for Methicillin-Resistant Staphylococcus aureus

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    Background: Screening at hospital admission for carriage of methicillin-resistant Staphylococcus aureus (MRSA) has been proposed as a strategy to reduce nosocomial infections. The objective of this study was to determine the long-term costs and health benefits of selective and universal screening for MRSA at hospital admission, using both PCR-based and chromogenic media-based tests in various settings. Methodology/Principal Findings: A simulation model of MRSA transmission was used to determine costs and effects over 15 years from a US healthcare perspective. We compared admission screening together with isolation of identified carriers against a baseline policy without screening or isolation. Strategies included selective screening of high risk patients or universal admission screening, with PCR-based or chromogenic media-based tests, in medium (5%) or high nosocomial prevalence (15%) settings. The costs of screening and isolation per averted MRSA infection were lowest using selective chromogenic-based screening in high and medium prevalence settings, at 4,100and4,100 and 10,300, respectively. Replacing the chromogenic-based test with a PCR-based test costs 13,000and13,000 and 36,200 per additional infection averted, and subsequent extension to universal screening with PCR would cost 131,000and131,000 and 232,700 per additional infection averted, in high and medium prevalence settings respectively. Assuming 17,645benefitperinfectionaverted,themostcostsavingstrategiesinhighandmediumprevalencesettingswereselectivescreeningwithPCRandselectivescreeningwithchromogenic,respectively.Conclusions/Significance:Admissionscreeningcosts17,645 benefit per infection averted, the most cost-saving strategies in high and medium prevalence settings were selective screening with PCR and selective screening with chromogenic, respectively. Conclusions/ Significance: Admission screening costs 4,100-$21,200 per infection averted, depending on strategy and setting. Including financial benefits from averted infections, screening could well be cost saving
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