1,694 research outputs found

    Functional anatomy of the middle and inner ears of the red fox, in comparison to domestic dogs and cats

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    Anatomical middle and inner ear parameters are often used to predict hearing sensitivities of mammalian species. Given that ear morphology is substantially affected both by phylogeny and body size, it is interesting to consider whether the relatively small anatomical differences expected in related species of similar size have a noticeable impact on hearing. We present a detailed anatomical description of the middle and inner ears of the red fox Vulpes vulpes, a widespread, wild carnivore for which a behavioural audiogram is available. We compare fox ears to those of the well‐studied and similarly sized domestic dog and cat, taking data for dogs and cats from the literature as well as providing new measurements of basilar membrane (BM) length and hair cell numbers and densities in these animals. Our results show that the middle ear of the red fox is very similar to that of dogs. The most obvious difference from that of the cat is the lack of a fully formed bony septum in the bulla tympanica of the fox. The cochlear structures of the fox, however, are very like those of the cat, whereas dogs have a broader BM in the basal cochlea. We further report that the mass of the middle ear ossicles and the bulla volume increase with age in foxes. Overall, the ear structures of foxes, dogs and cats are anatomically very similar, and their behavioural audiograms overlap. However, the results of several published models and correlations that use middle and inner ear measurements to predict aspects of hearing were not always found to match well with audiogram data, especially when it came to the sharper tuning in the fox audiogram. This highlights that, although there is evidently a broad correspondence between structure and function, it is not always possible to draw direct links when considering more subtle differences between related species

    Solution of the Dyson--Schwinger equation on de Sitter background in IR limit

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    We propose an ansatz which solves the Dyson-Schwinger equation for the real scalar fields in Poincare patch of de Sitter space in the IR limit. The Dyson-Schwinger equation for this ansatz reduces to the kinetic equation, if one considers scalar fields from the principal series. Solving the latter equation we show that under the adiabatic switching on and then off the coupling constant the Bunch-Davies vacuum relaxes in the future infinity to the state with the flat Gibbons-Hawking density of out-Jost harmonics on top of the corresponding de Sitter invariant out-vacuum.Comment: 20 pages, including 4 pages of Appendix. Acknowledgements correcte

    Catalytic activation of pre-substrates via dynamic Fragment assembly on Protein templates

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    Sensitive detection of small molecule fragments binding to defined sites of biomacromolecules is still a considerable challenge. Here we demonstrate that protein-binding fragments are able to induce enzymatic reactions on the protein surface via dynamic fragment ligation. Fragments binding to the S1 pocket of serine proteases containing a nitrogen, oxygen or sulphur nucleophile are found to activate electrophilic pre-substrates through a reversible, covalent ligation reaction. The dynamic ligation reaction positions the pre-substrate molecule at the active site of the protein thereby inducing its enzymatic cleavage. Catalytic activation of pre-substrates is confirmed by fluorescence spectroscopy and by high-performance liquid chromatography. The approach is investigated with 3 pre-substrates and 14 protein-binding fragments and the specific activation and the templating effect exerted by the enzyme is quantified for each protease–fragment–pre- substrate combination. The described approach enables the site-specific identification of protein-binding fragments, the functional characterization of enzymatic sites and the quantitative analysis of protein template-assisted ligation reactions. View full text Subject terms: Chemical sciences Chemical biology Medicinal chemistry At a glance Figures First | 1-4 of 6 | Last View all figures left The concept of pre-substrate activation by protein-binding fragments. Figure 1 Proof-of-concept. Figure 2 Structure of potential pre- substrates 1–3 and S1-binding fragments 4–17. Figure 3 Model for the activation of pre-substrates by nucleophilic protein-binding fragments. Figure 4 Activation of pre-substrate 3. Figure 5 Three-fragment assembly. Figure 6 right Compounds Genes and Proteins References Abstract• References• Author information• Supplementary information Rees, D. C., Congreve, M., Murray, C. W. & Carr, R. Fragment-based lead discovery. Nat. Rev. Drug Discov. 3, 660–672 (2004). 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Discovery of potent inhibitors of dihydroneopterin aldolase using CrystaLEAD high-throughput X-ray crystallographic screening and structure-directed lead optimization. J. Med. Chem. 47, 1709–1718 (2004). CAS ISI PubMed Article Patterson, A. W., Wood, W. J. L. & Ellman, J. A. Substrate activity screening (SAS): a general procedure for the preparation and screening of a fragment-based non-peptidic protease substrate library for inhibitor discovery. Nat. Protoc. 2, 424–433 (2007). ISI PubMed Article Mares-Guia, M. & Shaw, E. Substrate side chain guanidines as model of the binding of amidines and studies on the active center of trypsin. J. Biol. Chem. 240, 1579–1585 (1965). CAS PubMed Schmidt, M. F. et al. Sensitized detection of inhibitory fragments and iterative development of non- peptidic protease inhibitors by dynamic ligation screening. Angew. Chem. Int. Ed. 47, 3275–3278 (2008). Article Schmidt, M. F., El-Dahshan, A., Keller, S. & Rademann, J. Selective identification of cooperatively binding fragments in a high-throughput ligation assay enables development of a picomolar caspase-3 inhibitor. Angew. Chem. Int. Ed. 48, 6346–6349 (2009). CAS Article Schmidt, M. F., Groves, M. & Rademann, J. Dynamic substrate enhancement for the identification of specific, second-site-binding fragments targeting a set of protein tyrosine phosphatases. Chembiochem 12, 2640–2646 (2011). ISI PubMed Article Al-Gharabli, S. I. et al. An efficient method for the synthesis of peptide aldehyde libraries employed in the discovery of reversible SARS coronavirus main protease (SARS-CoV Mpro) inhibitors. Chembiochem 7, 1048–1055 (2006). ISI PubMed Article Reek J. N. H., Otto S. (eds)Dynamic Combinatorial Chemistry Wiley-VCH (2010). Osowska, K. & Miljanic, O. S. Oxidative kinetic self-sorting of a dynamic imine library. J. Am. Chem. Soc. 133, 724–727 (2011). ISI PubMed Article Hermann, A. 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CAS ISI Article Download references Author information Abstract• References• Author information• Supplementary information Affiliations Institute of Pharmacy, Medicinal Chemistry, University of Leipzig, Brüderstraße 34, 04103 Leipzig, Germany Edyta Burda & Jörg Rademann Institute of Pharmacy, Medicinal Chemistry, Freie Universität Berlin, Königin-Luise-Straße 2+4, 14195 Berlin, Germany Jörg Rademann Contributions J.R. and E.B. conceived and designed the experiments, E.B. performed the experiments. Both authors discussed the results and co-wrote the manuscript. Competing financial interests The authors declare no competing financial interests. Corresponding author Correspondence to: Jörg Rademann Supplementary information Abstract• References• Author information• Supplementary information PDF files Supplementary Information (915 KB) Supplementary Figures 1-11, Supplementary Methods and Supplementary References. Additional data 3-Oxo-(N-(4-methyl-2-oxo-2H- chromen-7-yl)-propanoylamide N-(4-Methyl-2-oxo-2H-chromen-7-yl)-acrylamide 3-((2-Aminoethyl)thio)-N-(4-methyl-2-oxo-2H-chromen-7-yl)propanamide npj Genomic Medicine - Open for Submissions Science jobs Science events NatureEvents Directory The 1st Annual Translational Microbiome Conference 14 May 2015 — 15 May 2015 Boston, MA, United States rTMS for depression, OCD and new developments: 2-day rTMS course 19 November 2015 — 20 November 2015 Bijleveldsingel 34, Nijmegen, Netherlands Human Health in the Face of Climate Change: Science, Medicine, and Adaptation 14 May 2015 — 15 May 2015 Carrer d' Isaac Newton, 26, Barcelona, Spain Post a free event More science events Discover more LIF negatively regulates tumour-suppressor p53 through Stat3/ID1/MDM2 in colorectal cancers Nature Communications 17 Oct 2014 Interlocked loops trigger lineage specification and stable fates in the Drosophila nervous system Nature Communications 28 Jul 2014 O-GlcNAc- modification of SNAP-29 regulates autophagosome maturation Nature Cell Biology 24 Nov 2014 Most read Nature.com Open innovation Pavillion Intravenous Sustained Release Drug Delivery Technology Deadline: Mar 21 2015 Reward: 30,000USDIntravenousdeliveryallowsfortherapiddistributionofinjecteddrugsfromtheveinsthroughouttheentirebody.OftentimWirelessInternetConnectivityforFieldApplicationsDeadline:Apr052015Reward:30,000 USD Intravenous delivery allows for the rapid distribution of injected drugs from the veins throughout the entire body. Oftentim… Wireless Internet Connectivity for Field Applications Deadline: Apr 05 2015 Reward: 20,000 USD Data collection in outdoor field studies is problematic and inefficient without a reliable wireless internet connection. The… Powered by:innocentive Sensitive detection of small molecule fragments binding to defined sites of biomacromolecules is still a considerable challenge. Here we demonstrate that protein-binding fragments are able to induce enzymatic reactions on the protein surface via dynamic fragment ligation. Fragments binding to the S1 pocket of serine proteases containing a nitrogen, oxygen or sulphur nucleophile are found to activate electrophilic pre-substrates through a reversible, covalent ligation reaction. The dynamic ligation reaction positions the pre-substrate molecule at the active site of the protein thereby inducing its enzymatic cleavage. Catalytic activation of pre-substrates is confirmed by fluorescence spectroscopy and by high-performance liquid chromatography. The approach is investigated with 3 pre-substrates and 14 protein-binding fragments and the specific activation and the templating effect exerted by the enzyme is quantified for each protease–fragment–pre- substrate combination. The described approach enables the site-specific identification of protein-binding fragments, the functional characterization of enzymatic sites and the quantitative analysis of protein template-assisted ligation reactions.1\. Auflag

    Asymmetric correlation matrices: an analysis of financial data

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    We analyze the spectral properties of correlation matrices between distinct statistical systems. Such matrices are intrinsically non symmetric, and lend themselves to extend the spectral analyses usually performed on standard Pearson correlation matrices to the realm of complex eigenvalues. We employ some recent random matrix theory results on the average eigenvalue density of this type of matrices to distinguish between noise and non trivial correlation structures, and we focus on financial data as a case study. Namely, we employ daily prices of stocks belonging to the American and British stock exchanges, and look for the emergence of correlations between two such markets in the eigenvalue spectrum of their non symmetric correlation matrix. We find several non trivial results, also when considering time-lagged correlations over short lags, and we corroborate our findings by additionally studying the asymmetric correlation matrix of the principal components of our datasets.Comment: Revised version; 11 pages, 13 figure

    Maximal entropy random walk in community finding

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    The aim of this paper is to check feasibility of using the maximal-entropy random walk in algorithms finding communities in complex networks. A number of such algorithms exploit an ordinary or a biased random walk for this purpose. Their key part is a (dis)similarity matrix, according to which nodes are grouped. This study encompasses the use of the stochastic matrix of a random walk, its mean first-passage time matrix, and a matrix of weighted paths count. We briefly indicate the connection between those quantities and propose substituting the maximal-entropy random walk for the previously chosen models. This unique random walk maximises the entropy of ensembles of paths of given length and endpoints, which results in equiprobability of those paths. We compare performance of the selected algorithms on LFR benchmark graphs. The results show that the change in performance depends very strongly on the particular algorithm, and can lead to slight improvements as well as significant deterioration.Comment: 7 pages, 4 figures, submitted to European Physical Journal Special Topics following the 4-th Conference on Statistical Physics: Modern Trends and Applications, July 3-6, 2012 Lviv, Ukrain

    Renal cell carcinoma drug and cell therapy: today and tomorrow

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    The paper also looks at clinically applicable targeted immune drugs and the principle of their effect on tumorous cells. Besides, modern clinical studies of cell drugs have been considere

    Portfolio Optimization and the Random Magnet Problem

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    Diversification of an investment into independently fluctuating assets reduces its risk. In reality, movement of assets are are mutually correlated and therefore knowledge of cross--correlations among asset price movements are of great importance. Our results support the possibility that the problem of finding an investment in stocks which exposes invested funds to a minimum level of risk is analogous to the problem of finding the magnetization of a random magnet. The interactions for this ``random magnet problem'' are given by the cross-correlation matrix {\bf \sf C} of stock returns. We find that random matrix theory allows us to make an estimate for {\bf \sf C} which outperforms the standard estimate in terms of constructing an investment which carries a minimum level of risk.Comment: 12 pages, 4 figures, revte

    Casimir effect for massless minimally coupled scalar field between parallel plates in de Sitter spacetime

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    Casimir effect for massless minimally coupled scalar field is studied. An explicit answer for de Sitter spacetime is obtained and analized. Cosmological implications of the result are discussed.Comment: 7 pages, 2 figure

    The Okun Misery Index in the European Union Countries from 2000 to 2009

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    The study is composed of four main parts and a summary. The first part, introduction, discusses various measures of the economic system's efficiency that are used in practice. Part two emphasises that the GDP per capita according to purchasing power parity still remains the most popular among those measures. Further, it presents the ranking of the European Union countries taking that measure into account, the research period being 1999-2009. Part three points out that it is also the level of poverty (misery) that determines the economic system's efficiency. That level can be measured by means of various indicators, among others, the so called HPI-2 index calculated by the UN. It will be the Okun misery index, however, computed as the sum of inflation and unemployment rates that will be presented as an alternative being of interest from the macroeconomic point of view. The ranking of the European Union member states according to that measure in the 2000-2004 and 2005-2009 periods will be provided in part four. The article will end in a summary containing synthetic conclusions drawn from earlier observations.Opracowanie składa się z czterech części zasadniczych i podsumowania. W punkcie pierwszym omówiono różnorodne mierniki sprawności systemu gospodarczego wykorzystywane w praktyce. W części drugiej podkreślono, iż nadal najpopularniejszym z nich jest PKB per capita według parytetu siły nabywczej. Zgodnie z tym miernikiem przedstawiono ranking państw Unii Europejskiej w latach 1999-2009. W punkcie trzecim podkreślono, że o sprawności systemu gospodarczego decyduje także poziom ubóstwa. Może być on mierzony różnymi wskaźnikami, m.in. tzw. indeksem HPI-2 obliczanym przez ONZ. Jako ciekawą z makroekonomicznego punktu widzenia alternatywę ukazano jednak miarę wskaźnika ubóstwa Okuna obliczanego poprzez zsumowanie stopy inflacji i stopy bezrobocia. Ranking państw Unii Europejskiej według tej miary w okresach 2000-2004 oraz 2005-2009 zaprezentowano w części czwartej. Całość zamknięto podsumowaniem, w którym zawarto syntetyczne wnioski z przeprowadzonych obserwacji

    Levy targeting and the principle of detailed balance

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    We investigate confined L\'{e}vy flights under premises of the principle of detailed balance. The master equation admits a transformation to L\'{e}vy - Schr\"{o}dinger semigroup dynamics (akin to a mapping of the Fokker-Planck equation into the generalized diffusion equation). We solve a stochastic targeting problem for arbitrary stability index 0<μ<20<\mu <2 of L\'{e}vy drivers: given an invariant probability density function (pdf), specify the jump - type dynamics for which this pdf is a long-time asymptotic target. Our ("μ\mu-targeting") method is exemplified by Cauchy family and Gaussian target pdfs. We solve the reverse engineering problem for so-called L\'{e}vy oscillators: given a quadratic semigroup potential, find an asymptotic pdf for the associated master equation for arbitrary μ\mu
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