10,131 research outputs found

    Fusion of twisted representations

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    The comultiplication formula for fusion products of untwisted representations of the chiral algebra is generalised to include arbitrary twisted representations. We show that the formulae define a tensor product with suitable properties, and determine the analogue of Zhu's algebra for arbitrary twisted representations. As an example we study the fusion of representations of the Ramond sector of the N=1 and N=2 superconformal algebra. In the latter case, certain subtleties arise which we describe in detail.Comment: 24 pages, LATE

    A Systems Biology Approach towards Deciphering the Unfolded Protein Response in Huntington's Disease

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    Although the disease causing gene huntingtin has been known for some time, the exact cause of neuronal cell death during _Huntington's disease_ (HD) remains unknown. One potential mechanism contributing to the massive loss of neurons in HD brains might be the _Unfolded Protein Response_ (UPR) which is activated by accumulation of misfolded proteins in the endoplasmic reticulum (ER). As an adaptive response, UPR upregulates transcription of chaperones, temporarily attenuating new translation and activates protein degradation via the proteasome. However, at high levels of ER stress, UPR signalling can contribute to neuronal apoptosis.

Our primary aims include (a) construction of the UPR signalling network, (b) curation and bioinformatical identification of UPR target genes and finally (c) examination of HD gene expression data sets for UPR transcriptional signatures and differential regulation of UPR pathways.

The UPR signalling pathway is reconstructed based on literature review and using the "Unified Interactome database":http://www.unihi.org. Lists of UPR target genes detected by previous experiments or as predicted by computational analysis are compiled. This allows us to perform enrichment analysis for differential HD gene expression and to assess whether UPR expression signatures are prominent during HD pathogenesis.

Results: The canonical UPR pathway is complemented with additional protein interaction data allowing us to assess its embedding into the cellular context and to identify potential modifiers as well as novel drug targets.

Conclusions: The in depth systems biology analysis can give us valuable insights about the involvement of the UPR in HD.
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    The Unfolded Protein Response and its potential role in Huntington's disease

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    Huntington's disease (HD) is a progressive, neurodegenerative disease with fatal outcome. Although the disease-causing gene (huntingtin) has been known for some time, the exact cause of neuronal cell death is still unknown. One potential mechanism contributing to the massive loss of neurons in the brain of HD patients might be the unfolded protein response (UPR), which is activated by accumulation of misfolded proteins in the endoplasmatic reticulum (ER). As an adaptive response to counter-balance accumulation of un- or misfolded proteins, the UPR upregulates transcription of chaperones, temporarily attenuates new translation, and activates protein degradation via the proteasome. However, it is known that persistent ER stress and activated UPR can cause cell death by triggering of apoptosis. Nevertheless, the evidence linking UPR with HD progression remains inconclusive. Here, we present first analyses of UPR activation during HD based on available expression data. To elucidate the potential role of UPR as a disease-relevant process, we examine its connection to cell death and inflammatory processes. Due to the complexity of these molecular mechanisms, a systems biology approach was pursued

    Intonation in unaccompanied singing: Accuracy, drift, and a model of reference pitch memory

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    Copyright 2014 Acoustical Society of America. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the Acoustical Society of America. The following article appeared in J. Acoust. Soc. Am. 136, 401 (2014) and may be found at http://dx.doi.org/10.1121/1.4881915

    Flow in linearly sheared two dimensional foams: from bubble to bulk scale

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    We probe the flow of two dimensional foams, consisting of a monolayer of bubbles sandwiched between a liquid bath and glass plate, as a function of driving rate, packing fraction and degree of disorder. First, we find that bidisperse, disordered foams exhibit strongly rate dependent and inhomogeneous (shear banded) velocity profiles, while monodisperse, ordered foams are also shear banded, but essentially rate independent. Second, we introduce a simple model based on balancing the averaged drag forces between the bubbles and the top plate and the averaged bubble-bubble drag forces. This model captures the observed rate dependent flows, and the rate independent flows. Third, we perform independent rheological measurements, both for ordered and disordered systems, and find these to be fully consistent with the scaling forms of the drag forces assumed in the simple model, and we see that disorder modifies the scaling. Fourth, we vary the packing fraction ϕ\phi of the foam over a substantial range, and find that the flow profiles become increasingly shear banded when the foam is made wetter. Surprisingly, our model describes flow profiles and rate dependence over the whole range of packing fractions with the same power law exponents -- only a dimensionless number kk which measures the ratio of the pre-factors of the viscous drag laws is seen to vary with packing fraction. We find that k∼(ϕ−ϕc)−1k \sim (\phi-\phi_c)^{-1}, where ϕc≈0.84\phi_c \approx 0.84, corresponding to the 2d jamming density, and suggest that this scaling follows from the geometry of the deformed facets between bubbles in contact. Overall, our work suggests a route to rationalize aspects of the ubiquitous Herschel-Bulkley (power law) rheology observed in a wide range of disordered materials.Comment: 16 pages, 14 figures, submitted to Phys. Rev. E. High quality version available at: http://www.physics.leidenuniv.nl/sections/cm/gr

    Mixtures of Charged Colloid and Neutral Polymer: Influence of Electrostatic Interactions on Demixing and Interfacial Tension

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    The equilibrium phase behavior of a binary mixture of charged colloids and neutral, non-adsorbing polymers is studied within free-volume theory. A model mixture of charged hard-sphere macroions and ideal, coarse-grained, effective-sphere polymers is mapped first onto a binary hard-sphere mixture with non-additive diameters and then onto an effective Asakura-Oosawa model [S. Asakura and F. Oosawa, J. Chem. Phys. 22, 1255 (1954)]. The effective model is defined by a single dimensionless parameter -- the ratio of the polymer diameter to the effective colloid diameter. For high salt-to-counterion concentration ratios, a free-volume approximation for the free energy is used to compute the fluid phase diagram, which describes demixing into colloid-rich (liquid) and colloid-poor (vapor) phases. Increasing the range of electrostatic interactions shifts the demixing binodal toward higher polymer concentration, stabilizing the mixture. The enhanced stability is attributed to a weakening of polymer depletion-induced attraction between electrostatically repelling macroions. Comparison with predictions of density-functional theory reveals a corresponding increase in the liquid-vapor interfacial tension. The predicted trends in phase stability are consistent with observed behavior of protein-polysaccharide mixtures in food colloids.Comment: 16 pages, 5 figure

    The Incidence and Clinical Relevance of Graft Hypertrophy After Matrix-Based Autologous Chondrocyte Implantation

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    Background: Graft hypertrophy is the most common complication of periosteal autologous chondrocyte implantation (p-ACI). Purpose: The aim of this prospective study was to analyze the development, the incidence rate, and the persistence of graft hypertrophy after matrix-based autologous chondrocyte implantation (mb-ACI) in the knee joint within a 2-year postoperative course. Study Design: Case series; Level of evidence, 4. Methods: Between 2004 and 2007, a total of 41 patients with 44 isolated cartilage defects of the knee were treated with the mb-ACI technique. The mean age of the patients was 35.8 years (standard deviation [SD], 11.3 years), and the mean body mass index was 25.9 (SD, 4.2; range, 19-35.3). The cartilage defects were arthroscopically classified as Outerbridge grades III and IV. The mean area of the cartilage defect measured 6.14 cm2 (SD, 2.3 cm2). Postoperative clinical and magnetic resonance imaging (MRI) examinations were conducted at 3, 6, 12, and 24 months to analyze the incidence and course of the graft. Results: Graft hypertrophy developed in 25% of the patients treated with mb-ACI within a postoperative course of 1 year; 16% of the patients developed hypertrophy grade 2, and 9% developed hypertrophy grade 1. Graft hypertrophy occurred primarily in the first 12 months and regressed in most cases within 2 years. The International Knee Documentation Committee (IKDC) and visual analog scale (VAS) scores improved during the postoperative follow-up time of 2 years. There was no difference between the clinical results regarding the IKDC and VAS pain scores and the presence of graft hypertrophy. Conclusion: The mb-ACI technique does not lead to graft hypertrophy requiring treatment as opposed to classic p-ACI. The frequency of occurrence of graft hypertrophy after p-ACI and mb-ACI is comparable. Graft hypertrophy can be considered as a temporary excessive growth of regenerative cartilage tissue rather than a true graft hypertrophy. It is therefore usually not a persistent or systematic complication in the treatment of circumscribed cartilage defects with mb-ACI

    Nonequilibrium fluctuation dissipation relations of interacting Brownian particles driven by shear

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    We present a detailed analysis of the fluctuation dissipation theorem (FDT) close to the glass transition in colloidal suspensions under steady shear using mode coupling approximations. Starting point is the many-particle Smoluchowski equation. Under shear, detailed balance is broken and the response functions in the stationary state are smaller at long times than estimated from the equilibrium FDT. An asymptotically constant relation connects response and fluctuations during the shear driven decay, restoring the form of the FDT with, however, a ratio different from the equilibrium one. At short times, the equilibrium FDT holds. We follow two independent approaches whose results are in qualitative agreement. To discuss the derived fluctuation dissipation ratios, we show an exact reformulation of the susceptibility which contains not the full Smoluchowski operator as in equilibrium, but only its well defined Hermitian part. This Hermitian part can be interpreted as governing the dynamics in the frame comoving with the probability current. We present a simple toy model which illustrates the FDT violation in the sheared colloidal system.Comment: 21 pages, 13 figures, submitted to Phys. Rev.

    Giant Magnetoelastic Effects in BaTiO3-based Extrinsic Multiferroic Hybrids

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    Extrinsic multiferroic hybrid structures consisting of ferromagnetic and ferroelectric layers elastically coupled to each other are promising due to their robust magnetoelectric effects even at room temperature. For a quantitative analysis of these magnetoelectric effects, a detailed knowledge of the piezoelectric and magnetoelastic behavior of both constituents as well as their mutual elastic coupling is mandatory. We here report on a theoretical and experimental study of the magnetic behavior of BaTiO3-based extrinsic multiferroic structures. An excellent agreement between molecular dynamics simulations and the experiments was found for Fe50Co50/BaTiO3 and Ni/BaTiO3 hybrid structures. This demonstrates that the magnetic behavior of extrinsic multiferroic hybrid structures can be determined by means of ab-initio calculations, allowing for the design of novel multiferroic hybrids
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