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Search Results: 1 - 10 of 220417 matches for " Markus Daμμe "
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Sedu??o e persuas?o: os "deliciosos" perigos da sofística
Silva, Markus Figueira da;
Cadernos CEDES , 2004, DOI: 10.1590/S0101-32622004000300005
Abstract: this paper updates a polemic that goes through the relations between philosophy and education, since the encounter among plato and the sophists: is it the virtue that has to be taught? is it politics? is it rhetoric? the thesis defended here is that the current dominion of the ignorance and the utility is a result of the regrettable result of the triumph from the ideals of the sophists over the platonic ones.
A No o Epicúrea de Eustatheía e a Téchne Hé Ietriké
Markus Figueira da Silva
Princípios : Revista de Filosofia , 1998,
Epicuro e a Morte como a Perda da Subjetividade
Markus Figueira da Silva
Princípios : Revista de Filosofia , 1995,
Ensaio acerca da imagem Poética: Bachelard e Jo o do Rio
Markus Figueira da Silva
Princípios : Revista de Filosofia , 1995,
Morte, de Giovanni Casertano
Markus Figueira da Silva
Princípios : Revista de Filosofia , 2004,
Abstract: Resenha do livro "Morte", de Giovanni Casertano.
Disruption of the Autophagy-Lysosome Pathway Is Involved in Neuropathology of the nclf Mouse Model of Neuronal Ceroid Lipofuscinosis
Melanie Thelen, Markus Daμμe, Michaela Schweizer, Christian Hagel, Andrew M.S. Wong, Jonathan D. Cooper, Thomas Braulke, Giovanna Galliciotti
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0035493
Abstract: Variant late-infantile neuronal ceroid lipofuscinosis, a fatal lysosomal storage disorder accompanied by regional atrophy and pronounced neuron loss in the brain, is caused by mutations in the CLN6 gene. CLN6 is a non-glycosylated endoplasmic reticulum (ER)-resident membrane protein of unknown function. To investigate mechanisms contributing to neurodegeneration in CLN6 disease we examined the nclf mouse, a naturally occurring model of the human CLN6 disease. Prominent autofluorescent and electron-dense lysosomal storage material was found in cerebellar Purkinje cells, thalamus, hippocampus, olfactory bulb and in cortical layer II to V. Another prominent early feature of nclf pathogenesis was the localized astrocytosis that was evident in many brain regions and the more widespread microgliosis. Expression analysis of mutant Cln6 found in nclf mice demonstrated synthesis of a truncated protein with a reduced half-life. Whereas the rapid degradation of the mutant Cln6 protein can be inhibited by proteasomal inhibitors, there was no evidence for ER stress or activation of the unfolded protein response in various brain areas during postnatal development. Age-dependent increases in LC3-II, ubiquitinated proteins, and neuronal p62-positive aggregates were observed, indicating a disruption of the autophagy-lysosome degradation pathway of proteins in brains of nclf mice, most likely due to defective fusion between autophagosomes and lysosomes. These data suggest that proteasomal degradation of mutant Cln6 is sufficient to prevent the accumulation of misfolded Cln6 protein, whereas lysosomal dysfunction impairs constitutive autophagy promoting neurodegeneration.
The Stack-Size of Combinatorial Tries Revisited
Markus E. Nebel
Discrete Mathematics & Theoretical Computer Science , 2002,
Abstract: In the present paper we consider a generalized class of extended binary trees in which leaves are distinguished in order to represent the location of a key within a trie of the same structure. We prove an exact asymptotic equivalent to the average stack-size of trees with α internal nodes and β leaves corresponding to keys; we assume that all trees with the same parameters α and β have the same probability. The assumption of that uniform model is motivated for example by the usage of tries for the compression of blockcodes. Furthermore, we will prove asymptotics for the r-th moments of the stack-size and we will show that a normalized stack-size possesses a theta distribution in the limit.
Applying Length-Dependent Stochastic Context-Free Grammars to RNA Secondary Structure Prediction
Frank Weinberg,Markus E. Nebel
Algorithms , 2011, DOI: 10.3390/a4040223
Abstract: In order to be able to capture effects from co-transcriptional folding, we extend stochastic context-free grammars such that the probability of applying a rule can depend on the length of the subword that is eventually generated from the symbols introduced by the rule, and we show that existing algorithms for training and for determining the most probable parse tree can easily be adapted to the extended model without losses in performance. Furthermore, we show that the extended model is suited to improve the quality of predictions of RNA secondary structures. The extended model may also be applied to other fields where stochastic context-free grammars are used like natural language processing. Additionally some interesting questions in the field of formal languages arise from it.
Evaluating the effect of disturbed ensemble distributions on SCFG based statistical sampling of RNA secondary structures
Anika Scheid, Markus E Nebel
BMC Bioinformatics , 2012, DOI: 10.1186/1471-2105-13-159
Abstract: In this work, we will consider the SCFG based approach in order to perform an analysis on how the quality of generated sample sets and the corresponding prediction accuracy changes when different degrees of disturbances are incorporated into the needed sampling probabilities. This is motivated by the fact that if the results prove to be resistant to large errors on the distinct sampling probabilities (compared to the exact ones), then it will be an indication that these probabilities do not need to be computed exactly, but it may be sufficient and more efficient to approximate them. Thus, it might then be possible to decrease the worst-case time requirements of such an SCFG based sampling method without significant accuracy losses. If, on the other hand, the quality of sampled structures can be observed to strongly react to slight disturbances, there is little hope for improving the complexity by heuristic procedures. We hence provide a reliable test for the hypothesis that a heuristic method could be implemented to improve the time scaling of RNA secondary structure prediction in the worst-case – without sacrificing much of the accuracy of the results.Our experiments indicate that absolute errors generally lead to the generation of useless sample sets, whereas relative errors seem to have only small negative impact on both the predictive accuracy and the overall quality of resulting structure samples. Based on these observations, we present some useful ideas for developing a time-reduced sampling method guaranteeing an acceptable predictive accuracy. We also discuss some inherent drawbacks that arise in the context of approximation. The key results of this paper are crucial for the design of an efficient and competitive heuristic prediction method based on the increasingly accepted and attractive statistical sampling approach. This has indeed been indicated by the construction of prototype algorithms.
Fbw7/hCDC4 dimerization regulates its substrate interactions
Markus Welcker, Bruce E Clurman
Cell Division , 2007, DOI: 10.1186/1747-1028-2-7
Abstract: We found that Fbw7 binds efficiently to itself through a domain just upstream of its F-box. We further show that dimerization is essential for the stable interaction of Fbw7 with the cyclin E T380 phospho-degron. Surprisingly, the requirement for dimerization can be suppressed by an additional phosphorylation of this phospho-degron at the +4 position (S384), which creates a binding site with higher affinity for monomeric Fbw7.Degradation of cyclin E by the Fbw7 pathway can, thus, be conditionally regulated either by Fbw7 dimerization or by hyperphosphorylation of the T380 phospho-degron. Other substrates, which cannot accommodate an extra phosphate in their phospho-degrons, or which don't provide a negatively charged amino acid in the +4 position, may be absolutely dependent on Fbw7 dimerization for their turnover. Our results point to an additional level of regulation for substrate interaction and turnover by Fbw7.Fbw7 is the mammalian homolog of budding yeast CDC4 and mediates the degradation of several proteins involved in cell growth and division, including cyclin E, c-Myc, c-Jun, Notch, Presenilin, and SREBP [1-10]. Fbw7 recognizes a phospho-epitope, termed CPD (for Cdc4 Phospho-Degron), contained within these substrates. Via its F-box, Fbw7 recruits the remainder of an SCF ubiquitin ligase complex, thus promoting substrate ubiquitination and rapid degradation by the proteasome [11]. Mammalian cells contain three Fbw7 isoforms (Fbw7α, Fbw7β, and Fbw7γ) that are produced by alternative splicing and that localize to the nucleoplasm, cytoplasm, and nucleolus, respectively [12-14].Numerous cancer-associated mutations have been identified within CPDs of Fbw7 substrates that render them insensitive to Fbw7 regulation. Accordingly, the Fbw7 gene is deleted in a large number of tumors. Moreover, many somatic point mutations have been found that eliminate Fbw7's function either by terminating the protein prematurely or disabling its substrate recognition domain, the C-t
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