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141.
This is an English translation of Paul Feyerabend's earliest extant essay “Der Begriff der Verständlichkeit in der modernen Physik” (1948). In it, Feyerabend defends positivism as a progressive framework for scientific research in certain stages of scientific development. He argues that in physics visualizability (Anschaulichkeit) and intelligibility (Verständlichkeit) are time-conditioned concepts: what is deemed visualizable in the development of physical theories is relative to a specific historical context and changes over time. He concludes that from time to time the abandonment of visualizability is crucial for progress in physics, as it is conducive to major theory change, illustrating the point on the basis of advances in atomic theory. 相似文献
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Vincent A. van der Mark Mohammed Ghiboub Casper Marsman Jing Zhao Remco van Dijk Johan K. Hiralall Kam S. Ho-Mok Zoë Castricum Wouter J. de Jonge Ronald P. J. Oude Elferink Coen C. Paulusma 《Cellular and molecular life sciences : CMLS》2017,74(4):715-730
P4-ATPases are lipid flippases that catalyze the transport of phospholipids to create membrane phospholipid asymmetry and to initiate the biogenesis of transport vesicles. Here we show, for the first time, that lipid flippases are essential to dampen the inflammatory response and to mediate the endotoxin-induced endocytic retrieval of Toll-like receptor 4 (TLR4) in human macrophages. Depletion of CDC50A, the β-subunit that is crucial for the activity of multiple P4-ATPases, resulted in endotoxin-induced hypersecretion of proinflammatory cytokines, enhanced MAP kinase signaling and constitutive NF-κB activation. In addition, CDC50A-depleted THP-1 macrophages displayed reduced tolerance to endotoxin. Moreover, endotoxin-induced internalization of TLR4 was strongly reduced and coincided with impaired endosomal MyD88-independent signaling. The phenotype of CDC50A-depleted cells was also induced by separate knockdown of two P4-ATPases, namely ATP8B1 and ATP11A. We conclude that lipid flippases are novel elements of the innate immune response that are essential to attenuate the inflammatory response, possibly by mediating endotoxin-induced internalization of TLR4. 相似文献
145.
This article studies Man and Tiao's (2006) low‐order autoregressive fractionally integrated moving‐average (ARFIMA) approximation to Tsai and Chan's (2005b) limiting aggregate structure of the long‐memory process. In matching the autocorrelations, we demonstrate that the approximation works well, especially for larger d values. In computing autocorrelations over long lags for larger d value, using the exact formula one might encounter numerical problems. The use of the ARFIMA(0, d, d?1) model provides a useful alternative to compute the autocorrelations as a really close approximation. In forecasting future aggregates, we demonstrate the close performance of using the ARFIMA(0, d, d?1) model and the exact aggregate structure. In practice, this provides a justification for the use of a low‐order ARFIMA model in predicting future aggregates of long‐memory process. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献
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Masroor Ahmad Bhat Rayees A. Zargar Anchit Modi Manju Aror N.K. Gaur 《自然科学进展(英文版)》2016,26(6):579-583
Silver ions substituted samarium strontium manganite (Sm0.55Sr0.30Ag0.15MnO3) pervoskite was synthesized by using respective oxides in stoichiometric ratio through solid state reaction. The as-prepared sample was characterized by various analytical techniques to confirm its formation and understand the effect of monovalent silver ions in pervoskite lattice. X-ray diffraction pattern confirms the single phase formation while grain morphology in SEM image indicates good connectivity among the grains. The enhancement in metal to insulator transition temperature shows quenched disorder and magnetoresistance phenomena. The magnetoresistance (MR) and temperature coefficient of resistance (TCR) emerge from grain growth factor and homogeneity induced by Ag+ ions in the lattice. The reduction in hysteresis loss resulted from antiferromagnetic - ferromagnetic (TN) and ferromagnetic - paramagnetic (Tc) transitions reveals the removal of disorder in perovskite lattice by Ag+ ions substitution. This increases the magnetic moment across distinct ions on the applying magnetic field. The rise in MR% (~99%) with silver doping emerging from smooth spin tunneling of the grains across the boundary and suppression of the disordered magnetic fluctuations with increase in magnetic field has been reported. The present compound exhibits the first order nature of magnetism and observed first time the highest value of TCR ~ 95%. 相似文献
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Novel neurotrophic factor CDNF protects and rescues midbrain dopamine neurons in vivo 总被引:1,自引:0,他引:1
Lindholm P Voutilainen MH Laurén J Peränen J Leppänen VM Andressoo JO Lindahl M Janhunen S Kalkkinen N Timmusk T Tuominen RK Saarma M 《Nature》2007,448(7149):73-77
In Parkinson's disease, brain dopamine neurons degenerate most prominently in the substantia nigra. Neurotrophic factors promote survival, differentiation and maintenance of neurons in developing and adult vertebrate nervous system. The most potent neurotrophic factor for dopamine neurons described so far is the glial-cell-line-derived neurotrophic factor (GDNF). Here we have identified a conserved dopamine neurotrophic factor (CDNF) as a trophic factor for dopamine neurons. CDNF, together with its previously described vertebrate and invertebrate homologue the mesencephalic-astrocyte-derived neurotrophic factor, is a secreted protein with eight conserved cysteine residues, predicting a unique protein fold and defining a new, evolutionarily conserved protein family. CDNF (Armetl1) is expressed in several tissues of mouse and human, including the mouse embryonic and postnatal brain. In vivo, CDNF prevented the 6-hydroxydopamine (6-OHDA)-induced degeneration of dopaminergic neurons in a rat experimental model of Parkinson's disease. A single injection of CDNF before 6-OHDA delivery into the striatum significantly reduced amphetamine-induced ipsilateral turning behaviour and almost completely rescued dopaminergic tyrosine-hydroxylase-positive cells in the substantia nigra. When administered four weeks after 6-OHDA, intrastriatal injection of CDNF was able to restore the dopaminergic function and prevent the degeneration of dopaminergic neurons in substantia nigra. Thus, CDNF was at least as efficient as GDNF in both experimental settings. Our results suggest that CDNF might be beneficial for the treatment of Parkinson's disease. 相似文献
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In developing progeny of mammals the two parental genomes are differentially expressed according to imprinting marks, and embryos with only a uniparental genetic contribution die. Gene expression that is dependent on the parent of origin has also been observed in the offspring of flowering plants, and mutations in the imprinting machinery lead to embryonic lethality, primarily affecting the development of the endosperm-a structure in the seed that nourishes the embryo, analogous to the function of the mammalian placenta. Here we have generated Arabidopsis thaliana seeds in which the endosperm is of uniparental, that is, maternal, origin. We demonstrate that imprinting in developing seeds can be bypassed and viable albeit smaller seedlings can develop from seeds lacking a paternal contribution to the endosperm. Bypassing is only possible if the mother is mutant for any of the FIS-class genes, which encode Polycomb group chromatin-modifying factors. Thus, these data provide functional evidence that the action of the FIS complex balances the contribution of the paternal genome. As flowering plants have evolved a special reproduction system with a parallel fusion of two female with two male gametes, our findings support the hypothesis that only with the evolution of double fertilization did the action of the FIS genes become a requirement for seed development. Furthermore, our data argue for a gametophytic origin of endosperm in flowering plants, thereby supporting a hypothesis raised in 1900 by Eduard Strasburger. 相似文献