2,836 research outputs found

    Semantics and Proof Theory of the Epsilon Calculus

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    The epsilon operator is a term-forming operator which replaces quantifiers in ordinary predicate logic. The application of this undervalued formalism has been hampered by the absence of well-behaved proof systems on the one hand, and accessible presentations of its theory on the other. One significant early result for the original axiomatic proof system for the epsilon-calculus is the first epsilon theorem, for which a proof is sketched. The system itself is discussed, also relative to possible semantic interpretations. The problems facing the development of proof-theoretically well-behaved systems are outlined.Comment: arXiv admin note: substantial text overlap with arXiv:1411.362

    Growth Hormone (GH)-Releasing Peptide Stimulation of GH Release from Human Somatotroph Adenoma Cells: Interaction with GH-Releasing Hormone, Thyrotropin- Releasing Hormone, and Octreotide.

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    The synthetic hexapeptide GH-releasing peptide (GHRP; His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) specifically stimulates GH secretion in humans in vivo and in animals in vitro and in vivo via a still unknown receptor and mechanism. To determine the effect of GHRP on human somatotroph cells in vitro, we stimulated cell cultures derived from 12 different human somatotroph adenomas with GHRP alone and in combination with GH-releasing hormone (GHRH), TRH, and the somatostatin analog octreotide. GH secretion of all 12 adenoma cultures could be stimulated with GHRP, whereas GHRH was active only in 6 adenoma cultures. In GHRH-responsive cell cultures, simultaneous application of GHRH and GHRP had an additive effect on GH secretion. TRH stimulated GH release in 4 of 7 adenoma cultures; in TRH-responsive cell cultures there was also an additive effect of GHRP and TRH on GH secretion. In 5 of 9 adenoma cultures investigated, octreotide inhibited basal GH secretion. In these cell cultures, GHRP-induced GH release was suppressed by octreotide. In 5 of 5 cases, the protein kinase-C inhibitor phloretin partly inhibited GHRP-stimulated GH release, but not basal GH secretion. In summary, GH secretion was stimulated by GHRP in all somatotroph adenomas investigated, indicating that its unknown receptor and signaling pathway are expressed more consistently in somatotroph adenoma cells than those for GHRH, TRH, and somatostatin. Our data give further evidence that GHRP-stimulated GH secretion is mediated by a receptor different from that for GHRH or TRH, respectively, and that protein kinase-C is involved in the signal transduction pathway. Because human somatotroph adenoma cell cultures respond differently to various neuropeptides (GHRH, TRH, somatostatin, and others), they provide a model for further investigation of the mechanism of action of GHRP-induced GH secretion

    Analytical study of the effect of recombination on evolution via DNA shuffling

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    We investigate a multi-locus evolutionary model which is based on the DNA shuffling protocol widely applied in \textit{in vitro} directed evolution. This model incorporates selection, recombination and point mutations. The simplicity of the model allows us to obtain a full analytical treatment of both its dynamical and equilibrium properties, for the case of an infinite population. We also briefly discuss finite population size corrections

    Uterine NK cells are critical in shaping DC immunogenic functions compatible with pregnancy progression.

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    Dendritic cell (DC) and natural killer (NK) cell interactions are important for the regulation of innate and adaptive immunity, but their relevance during early pregnancy remains elusive. Using two different strategies to manipulate the frequency of NK cells and DC during gestation, we investigated their relative impact on the decidualization process and on angiogenic responses that characterize murine implantation. Manipulation of the frequency of NK cells, DC or both lead to a defective decidual response characterized by decreased proliferation and differentiation of stromal cells. Whereas no detrimental effects were evident upon expansion of DC, NK cell ablation in such expanded DC mice severely compromised decidual development and led to early pregnancy loss. Pregnancy failure in these mice was associated with an unbalanced production of anti-angiogenic signals and most notably, with increased expression of genes related to inflammation and immunogenic activation of DC. Thus, NK cells appear to play an important role counteracting potential anomalies raised by DC expansion and overactivity in the decidua, becoming critical for normal pregnancy progression

    Irreversible Performance of a Quantum Harmonic Heat Engine

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    The unavoidable irreversible losses of power in a heat engine are found to be of quantum origin. Following thermodynamic tradition a model quantum heat engine operating by the Otto cycle is analyzed. The working medium of the model is composed of an ensemble of harmonic oscillators. A link is established between the quantum observables and thermodynamical variables based on the concept of canonical invariance. These quantum variables are sufficient to determine the state of the system and with it all thermodynamical variables. Conditions for optimal work, power and entropy production show that maximum power is a compromise between the quasistatic limit of adiabatic following on the compression and expansion branches and a sudden limit of very short time allocation to these branches. At high temperatures and quasistatic operating conditions the efficiency at maximum power coincides with the endoreversible result. The optimal compression ratio varies from the square root of the temperature ratio in the quasistatic limit where their reversibility is dominated by heat conductance to the temperature ratio to the power of 1/4 in the sudden limit when the irreversibility is dominated by friction. When the engine deviates from adiabatic conditions the performance is subject to friction. The origin of this friction can be traced to the noncommutability of the kinetic and potential energy of the working medium.Comment: 25 pages, 7 figures. Revision added explicit heat-transfer expression and extended the discussion on the quantum origin of frictio

    About the role of visual field defects in pure alexia

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    Pure alexia is an acquired reading disorder characterized by a disproportionate prolongation of reading time as a function of word length. Although the vast majority of cases reported in the literature show a right-sided visual defect, little is known about the contribution of this low-level visual impairment to their reading difficulties. The present study was aimed at investigating this issue by comparing eye movement patterns during text reading in six patients with pure alexia with those of six patients with hemianopic dyslexia showing similar right-sided visual field defects. We found that the role of the field defect in the reading difficulties of pure alexics was highly deficit-specific. While the amplitude of rightward saccades during text reading seems largely determined by the restricted visual field, other visuo-motor impairments—particularly the pronounced increases in fixation frequency and viewing time as a function of word length—may have little to do with their visual field defect. In addition, subtracting the lesions of the hemianopic dyslexics from those found in pure alexics revealed the largest group differences in posterior parts of the left fusiform gyrus, occipito-temporal sulcus and inferior temporal gyrus. These regions included the coordinate assigned to the centre of the visual word form area in healthy adults, which provides further evidence for a relation between pure alexia and a damaged visual word form area. Finally, we propose a list of three criteria that may improve the differential diagnosis of pure alexia and allow appropriate therapy recommendation

    Metabolomics reveals effects of maternal smoking on endogenous metabolites from lipid metabolism in cord blood of newborns

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    Introduction: A general detrimental effect of smoking during pregnancy on the health of newborn children is well-documented, but the detailed mechanisms remain elusive. Objectives: Beside the specific influence of environmental tobacco smoke derived toxicants on developmental regulation the impact on the metabolism of newborn children is of particular interest, first as a general marker of foetal development and second due to its potential predictive value for the later occurrence of metabolic diseases. Methods: Tobacco smoke exposure information from a questionnaire was confirmed by measuring the smoking related metabolites S-Phenyl mercapturic acid, S-Benzyl mercapturic acid and cotinine in maternal urine by LC–MS/MS. The impact of smoking on maternal endogenous serum metabolome and children’s cord blood metabolome was assessed in a targeted analysis of 163 metabolites by an LC–MS/MS based assay. The anti-oxidative status of maternal serum samples was analysed by chemoluminiscence based method. Results: Here we present for the first time results of a metabolomic assessment of the cordblood of 40 children and their mothers. Several analytes from the group of phosphatidylcholines, namely PCaaC28:1, PCaaC32:3, PCaeC30:1, PCaeC32:2, PCaeC40:1, and sphingomyelin SM C26:0, differed significantly in mothers and children’s sera depending on smoking status. In serum of smoking mothers the antioxidative capacity of water soluble compounds was not significantly changed while there was a significant decrease in the lipid fraction. Conclusion: Our data give evidence that smoking during pregnancy alters both the maternal and children’s metabolome. Whether the different pattern found in adults compared to newborn children could be related to different disease outcomes should be in the focus of future studies

    Spirometry reference equations for central European populations from school age to old age.

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    Spirometry reference values are important for the interpretation of spirometry results. Reference values should be updated regularly, derived from a population as similar to the population for which they are to be used and span across all ages. Such spirometry reference equations are currently lacking for central European populations. To develop spirometry reference equations for central European populations between 8 and 90 years of age. We used data collected between January 1993 and December 2010 from a central European population. The data was modelled using "Generalized Additive Models for Location, Scale and Shape" (GAMLSS). The spirometry reference equations were derived from 118'891 individuals consisting of 60'624 (51%) females and 58'267 (49%) males. Altogether, there were 18'211 (15.3%) children under the age of 18 years. We developed spirometry reference equations for a central European population between 8 and 90 years of age that can be implemented in a wide range of clinical settings

    Ricci curvature of finite Markov chains via convexity of the entropy

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    We study a new notion of Ricci curvature that applies to Markov chains on discrete spaces. This notion relies on geodesic convexity of the entropy and is analogous to the one introduced by Lott, Sturm, and Villani for geodesic measure spaces. In order to apply to the discrete setting, the role of the Wasserstein metric is taken over by a different metric, having the property that continuous time Markov chains are gradient flows of the entropy. Using this notion of Ricci curvature we prove discrete analogues of fundamental results by Bakry--Emery and Otto--Villani. Furthermore we show that Ricci curvature bounds are preserved under tensorisation. As a special case we obtain the sharp Ricci curvature lower bound for the discrete hypercube.Comment: 39 pages, to appear in Arch. Ration. Mech. Ana
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