966 research outputs found

    La recepción de la Política aristotélica y el desarrollo del concepto de Estado en el Medioevo tardío en Tomás de Aquino y Marsilio de Padua

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    The author analyzes the contribution of Aristotle’s Politics to the process of separation between theology and politics, in which the predominance of political theology concludes. He emphasizes specially three aspects of Aristotelian thought and their influence on this process: Aristotle answers the question about the origins of state authority; he considers the human community as a genuine dimension of the reality; his practical philosophy offers elements to distinguish between politics and ethics. Finally, the author studies the autonomy of politics in the political thought of Aquinas and Marsilius of Padua.Este trabajo analiza la contribución de la Política de Aristóteles al proceso de separación entre la teología y la política, que le da fin a la predominancia de la teología política. Se enfaniza centralmente en tres aspectos del pensamiento aristotélico y su influencia en este proceso: la respuesta de Aristóteles a la cuestión acerca de los orígenes de la autoridad estatal; la comunidad humana como una dimensión genuina de la realidad y su filosofía práctica que brinda elementos para distinguir entre la política y la ética. Finalmente, se estudia la autonomía de la política en el pensamiento político de Tomás de Aquino y Marsilio de Padua

    Natural ligand motifs of H-2E molecules are allele specific and illustrate homology to HLA-DR molecules

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    Motifs of peptldes naturally associated with H-2Ek and Ed molecules were determined by (i) pool sequencing of natural ligand mixtures and (ii) sequencing of individual natural ligands followed by their alignment to the basic motif suggested by pool sequencing. The data reveal nine amino acid motifs with interaction sites at relative positions P1, P4, P6 and P9, with specificities that are identical at some but different at other anchor positions between Ed and Ek motifs, illustrating the different requirements for peptides to be presented by these two MHC molecules. The anchors with the most restricted specificity are P1 and P9. P1 is aliphatic for Ek and predominantly aromatic for Ed. P9 is positively charged for both molecules. P4 and P6 show a totally different amino acid preference between Ek and Ed ligand motifs. An alignment of Ed and Ek protein sequences to the recently reported HLA-DR1 pocket residues is in agreement with observed anchor residues in Ek and Ed motifs, thus confirming the predicted similarity of mouse class II E molecules with human DR molecules. Furthermore, this alignment was extended to the putative pockets of class II Eb and E* molecules, and allowed, together with sequence information of previously Identified natural ligands of Eb and E5 molecules, a prediction of their respective motifs. The information obtained by this study should be useful to identify putative class II E epltopes in proteins and to design peptides for blocking class II E molecule

    Identification of Zoophilic Dermatophytes Using MALDI-TOF Mass Spectrometry

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    Dermatophytoses represent a major health burden in animals and man. Zoophilic dermatophytes usually show a high specificity to their original animal host but a zoonotic transmission is increasingly recorded. In humans, these infections elicit highly inflammatory skin lesions requiring prolonged therapy even in the immunocompetent patient. The correct identification of the causative agent is often crucial to initiate a targeted and effective therapy. To that end, matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) represents a promising tool. The objective of this study was to evaluate the reliability of species identification of zoophilic dermatophytes using MALDI-TOF MS. The investigation of isolates from veterinary clinical samples suspicious of dermatophytoses suggests a good MALDI-TOF MS based identification of the most common zoophilic dermatophyte Microsporum canis. Trichophyton (T.) spp. usually achieved scores only around the cutoff value for secure species identification because of a small number of reference spectra. Moreover, these results need to be interpreted with caution due to the close taxonomic relationship of dermatophytes being reflected in very similar spectra. In our study, the analysis of 50 clinical samples of hedgehogs revealed no correct identification using the provided databases, nor for zoophilic neither for geophilic causative agents. After DNA sequencing, adaptation of sample processing and an individual extension of the inhouse database, acceptable identification scores were achieved (T. erinacei and Arthroderma spp., respectively). A score-oriented distance dendrogram revealed clustering of geophilic isolates of four different species of the genus Arthroderma and underlined the close relationship of the important zoophilic agents T. erinacei, T. verrucosum and T. benhamiae by forming a subclade within a larger cluster including different dermatophytes. Taken together, MALDI-TOF MS proofed suitable for the identification of zoophilic dermatophytes provided fresh cultures are used and the reference library was previously extended with spectra of laboratory-relevant species. Performing independent molecular methods, such as sequencing, is strongly recommended to substantiate the findings from morphologic and MALDI-TOF MS analyses, especially for uncommon causative agents

    Resveratrol differentially regulates NAMPT and SIRT1 in hepatocarcinoma cells and primary human hepatocytes

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    Resveratrol is reported to possess chemotherapeutic properties in several cancers. In this study, we wanted to investigate the molecular mechanisms of resveratrol-induced cell cycle arrest and apoptosis as well as the impact of resveratrol on NAMPT and SIRT1 protein function and asked whether there are differences in hepatocarcinoma cells (HepG2, Hep3B cells) and non-cancerous primary human hepatocytes. We found a lower basal NAMPT mRNA and protein expression in hepatocarcinoma cells compared to primary hepatocytes. In contrast, SIRT1 was significantly higher expressed in hepatocarcinoma cells than in primary hepatocytes. Resveratrol induced cell cycle arrest in the S- and G2/M- phase and apoptosis was mediated by activation of p53 and caspase-3 in HepG2 cells. In contrast to primary hepatocytes, resveratrol treated HepG2 cells showed a reduction of NAMPT enzymatic activity and increased p53 acetylation (K382). Resveratrol induced NAMPT release from HepG2 cells which was associated with increased NAMPT mRNA expression. This effect was absent in primary hepatocytes where resveratrol was shown to function as NAMPT and SIRT1 activator. SIRT1 inhibition by EX527 resembled resveratrol effects on HepG2 cells. Furthermore, a SIRT1 overexpression significantly decreased both p53 hyperacetylation and resveratrol-induced NAMPT release as well as S-phase arrest in HepG2 cells. We could show that NAMPT and SIRT1 are differentially regulated by resveratrol in hepatocarcinoma cells and primary hepatocytes and that resveratrol did not act as a SIRT1 activator in hepatocarcinoma cells

    Embrace the Gap: VAEs Perform Independent Mechanism Analysis

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    Variational autoencoders (VAEs) are a popular framework for modeling complex data distributions; they can be efficiently trained via variational inference by maximizing the evidence lower bound (ELBO), at the expense of a gap to the exact (log-)marginal likelihood. While VAEs are commonly used for representation learning, it is unclear why ELBO maximization would yield useful representations, since unregularized maximum likelihood estimation cannot invert the data-generating process. Yet, VAEs often succeed at this task. We seek to elucidate this apparent paradox by studying nonlinear VAEs in the limit of near-deterministic decoders. We first prove that, in this regime, the optimal encoder approximately inverts the decoder -- a commonly used but unproven conjecture -- which we refer to as {\em self-consistency}. Leveraging self-consistency, we show that the ELBO converges to a regularized log-likelihood. This allows VAEs to perform what has recently been termed independent mechanism analysis (IMA): it adds an inductive bias towards decoders with column-orthogonal Jacobians, which helps recovering the true latent factors. The gap between ELBO and log-likelihood is therefore welcome, since it bears unanticipated benefits for nonlinear representation learning. In experiments on synthetic and image data, we show that VAEs uncover the true latent factors when the data generating process satisfies the IMA assumption.Comment: 47 pages, accepted at NeurIPS202

    Highly Efficient and Scalable Separation of Semiconducting Carbon Nanotubes via Weak Field Centrifugation

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    The identification of scalable processes that transfer random mixtures of single-walled carbon nanotubes (SWCNTs) into fractions featuring a high content of semiconducting species is crucial for future application of SWCNTs in high-performance electronics. Herein we demonstrate a highly efficient and simple separation method that relies on selective interactions between tailor-made amphiphilic polymers and semiconducting SWCNTs in the presence of low viscosity separation media. High purity individualized semiconducting SWCNTs or even self-organized semiconducting sheets are separated from an as-produced SWCNT dispersion via a single weak field centrifugation run. Absorption and Raman spectroscopy are applied to verify the high purity of the obtained SWCNTs. Furthermore SWCNT - network field-effect transistors were fabricated, which exhibit high ON/OFF ratios (105^{5}) and field-effect mobilities (17 cm2^{2}/Vs). In addition to demonstrating the feasibility of high purity separation by a novel low complexity process, our method can be readily transferred to large scale production
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