784 research outputs found

    Network growth models and genetic regulatory networks

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    We study a class of growth algorithms for directed graphs that are candidate models for the evolution of genetic regulatory networks. The algorithms involve partial duplication of nodes and their links, together with innovation of new links, allowing for the possibility that input and output links from a newly created node may have different probabilities of survival. We find some counterintuitive trends as parameters are varied, including the broadening of indegree distribution when the probability for retaining input links is decreased. We also find that both the scaling of transcription factors with genome size and the measured degree distributions for genes in yeast can be reproduced by the growth algorithm if and only if a special seed is used to initiate the process.Comment: 8 pages with 7 eps figures; uses revtex4. Added references, cleaner figure

    Scaling property of the critical hopping parameters for the Bose-Hubbard model

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    Recently precise results for the boundary between the Mott insulator phase and the superfluid phase of the homogeneous Bose-Hubbard model have become available for arbitrary integer filling factor g and any lattice dimension d > 1. We use these data for demonstrating that the critical hopping parameters obey a scaling relationship which allows one to map results for different g onto each other. Unexpectedly, the mean-field result captures the dependence of the exact critical parameters on the filling factor almost fully. We also present an approximation formula which describes the critical parameters for d > 1 and any g with high accuracy.Comment: 5 pages, 5 figures. to appear in EPJ

    Sex-dependent influence of endogenous estrogen in pulmonary hypertension

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    Rationale: The incidence of pulmonary arterial hypertension (PAH) is greater in women suggesting estrogens may play a role in the disease pathogenesis. Experimentally, in males exogenously administered estrogen can protect against PH; however in models that display female susceptibility estrogens may play a causative role. Objectives: To clarify the influence of endogenous estrogen and gender in PH and assess the therapeutic potential of a clinically available aromatase inhibitor. Methods: We interrogated the effect of reduced endogenous estrogen in males and females using the aromatase inhibitor, anastrozole, in two models of PH; the hypoxic mouse and Sugen 5416/hypoxic rat. We also determined the effects of gender on pulmonary expression of aromatase in these models and in lungs from PAH patients. Results: Anastrozole attenuated PH in both models studied, but only in females. To verify this effect was due to reduced estrogenic activity we confirmed that in hypoxic mice inhibition of estrogen receptor alpha also has a therapeutic effect specifically in females. Female rodent lung displays increased aromatase and decreased BMPR2 and Id1 expression compared to male. Anastrozole treatment reversed the impaired BMPR2 pathway in females. Increased aromatase expression was also detected in female human pulmonary artery smooth muscle cells compared to male. Conclusions: The unique phenotype of female pulmonary arteries facilitates the therapeutic effects of anastrozole in experimental PH confirming a role for endogenous estrogen in the disease pathogenesis in females and suggests aromatase inhibitors may have therapeutic potential

    'A new kind of rays': gothic fears, cultural anxieties and the discovery of X-rays in the 1890s

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    In 1895, the world of modern physics was effectively ushered in with the discovery of X-rays by the German physicist, Wilhelm Conrad Röntgen. X-rays rapidly changed the ways in which the human body was perceived, and their discovery was documented and fiercely debated in scientific articles, newspaper reports, literary writings, cartoons and films. This article examines a range of these responses, both 'scientific' and 'popular', and considers the particular significance of their repeated recourse to the Gothic and the uncanny as a means of expressing both excitement and disquiet at what the new X-ray phenomenon might mean

    Neutralization of SARS-CoV-2 by highly potent, hyperthermostable, and mutation-tolerant nanobodies

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    Monoclonal anti-SARS-CoV-2 immunoglobulins represent a treatment option for COVID-19. However, their production in mammalian cells is not scalable to meet the global demand. Single-domain (VHH) antibodies (also called nanobodies) provide an alternative suitable for microbial production. Using alpaca immune libraries against the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein, we isolated 45 infection-blocking VHH antibodies. These include nanobodies that can withstand 95°C. The most effective VHH antibody neutralizes SARS-CoV-2 at 17–50 pM concentration (0.2–0.7 µg per liter), binds the open and closed states of the Spike, and shows a tight RBD interaction in the X-ray and cryo-EM structures. The best VHH trimers neutralize even at 40 ng per liter. We constructed nanobody tandems and identified nanobody monomers that tolerate the K417N/T, E484K, N501Y, and L452R immune-escape mutations found in the Alpha, Beta, Gamma, Epsilon, Iota, and Delta/Kappa lineages. We also demonstrate neutralization of the Beta strain at low-picomolar VHH concentrations. We further discovered VHH antibodies that enforce native folding of the RBD in the E. coli cytosol, where its folding normally fails. Such “fold-promoting” nanobodies may allow for simplified production of vaccines and their adaptation to viral escape-mutations

    Cell shape analysis of random tessellations based on Minkowski tensors

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    To which degree are shape indices of individual cells of a tessellation characteristic for the stochastic process that generates them? Within the context of stochastic geometry and the physics of disordered materials, this corresponds to the question of relationships between different stochastic models. In the context of image analysis of synthetic and biological materials, this question is central to the problem of inferring information about formation processes from spatial measurements of resulting random structures. We address this question by a theory-based simulation study of shape indices derived from Minkowski tensors for a variety of tessellation models. We focus on the relationship between two indices: an isoperimetric ratio of the empirical averages of cell volume and area and the cell elongation quantified by eigenvalue ratios of interfacial Minkowski tensors. Simulation data for these quantities, as well as for distributions thereof and for correlations of cell shape and volume, are presented for Voronoi mosaics of the Poisson point process, determinantal and permanental point processes, and Gibbs hard-core and random sequential absorption processes as well as for Laguerre tessellations of polydisperse spheres and STIT- and Poisson hyperplane tessellations. These data are complemented by mechanically stable crystalline sphere and disordered ellipsoid packings and area-minimising foam models. We find that shape indices of individual cells are not sufficient to unambiguously identify the generating process even amongst this limited set of processes. However, we identify significant differences of the shape indices between many of these tessellation models. Given a realization of a tessellation, these shape indices can narrow the choice of possible generating processes, providing a powerful tool which can be further strengthened by density-resolved volume-shape correlations.Comment: Chapter of the forthcoming book "Tensor Valuations and their Applications in Stochastic Geometry and Imaging" in Lecture Notes in Mathematics edited by Markus Kiderlen and Eva B. Vedel Jense

    Spectral fiber dosimetry with beryllium oxide for quality assurance in hadron radiation therapy

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    Using the radioluminescence light of solid state probes coupled to long and flexible fibers for dosimetry in radiotherapy offers many advantages in terms of probe size, robustness and cost efficiency. However, especially in hadron fields, radioluminophores exhibit quenching effects dependent on the linear energy transfer. This work describes the discovery of a spectral shift in the radioluminescence light of beryllium oxide in dependence on the residual range at therapeutic proton energies. A spectrally resolving measurement setup has been developed and tested in scanned proton fields. It is shown that such a system can not only quantitatively reconstruct the dose, but might also give information on the residual proton range at the point of measurement
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