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221.
This paper aims to show that the development of Feyerabend's philosophical ideas in the 1950s and 1960s largely took place in the context of debates on quantum mechanics.In particular, he developed his influential arguments for pluralism in science in discussions with the quantum physicist David Bohm, who had developed an alternative approach to quantum physics which (in Feyerabend's perception) was met with a dogmatic dismissal by some of the leading quantum physicists. I argue that Feyerabend's arguments for theoretical pluralism and for challenging established theories were connected to his objections to the dogmatism and conservatism he observed in quantum physics.However, as Feyerabend gained insight into the physical details and historical complexities which led to the development of quantum mechanics, he gradually became more modest in his criticisms. His writings on quantum mechanics especially engaged with Niels Bohr; initially, he was critical of Bohr's work in quantum mechanics, but in the late 1960s, he completely withdrew his criticism and even praised Bohr as a model scientist. He became convinced that however puzzling quantum mechanics seemed, it was methodologically unobjectionable – and this was crucial for his move towards ‘anarchism’ in philosophy of science. 相似文献
222.
Vonk WI de Bie P Wichers CG van den Berghe PV van der Plaats R Berger R Wijmenga C Klomp LW van de Sluis B 《Cellular and molecular life sciences : CMLS》2012,69(1):149-163
Menkes disease (MD) is an X-linked recessive disorder characterized by copper deficiency resulting in a diminished function
of copper-dependent enzymes. Most MD patients die in early childhood, although mild forms of MD have also been described.
A diversity of mutations in the gene encoding of the Golgi-resident copper-transporting P1B-type ATPase ATP7A underlies MD. To elucidate the molecular consequences of the ATP7A mutations, various mutations in ATP7A associated with distinct phenotypes of MD (L873R, C1000R, N1304S, and A1362D) were analyzed in detail. All mutants studied
displayed changes in protein expression and intracellular localization parallel to a dramatic decline in their copper-transporting
capacity compared to ATP7A the wild-type. We restored these observed defects in ATP7A mutant proteins by culturing the cells
at 30°C, which improves the quality of protein folding, similar to that which as has recently has been demonstrated for misfolded
ATP7B, a copper transporter homologous to ATP7A. Further, the effect of the canine copper toxicosis protein COMMD1 on ATP7A
function was examined as COMMD1 has been shown to regulate the proteolysis of ATP7B proteins. Interestingly, in addition to
adjusted growth temperature, binding of COMMD1 partially restored the expression, subcellular localization, and copper-exporting
activities of the ATP7A mutants. However, no effect of pharmacological chaperones was observed. Together, the presented data
might provide a new direction for developing therapies to improve the residual exporting activity of unstable ATP7A mutant
proteins, and suggests a potential role for COMMD1 in this process. 相似文献
223.
J. M. de Vries M. L. C. Hagemans J. B. J. Bussmann A. T. van der Ploeg P. A. van Doorn 《Cellular and molecular life sciences : CMLS》2010,67(5):701-713
Fatigue accounts for an important part of the burden experienced by patients with neuromuscular disorders. Substantial high
prevalence rates of fatigue are reported in a wide range of neuromuscular disorders, such as Guillain–Barré syndrome and Pompe
disease. Fatigue can be subdivided into experienced fatigue and physiological fatigue. Physiological fatigue in turn can be
of central or peripheral origin. Peripheral fatigue is an important contributor to fatigue in neuromuscular disorders, but
in reaction to neuromuscular disease fatigue of central origin can be an important protective mechanism to restrict further
damage. In most cases, severity of fatigue seems to be related with disease severity, possibly with the exception of fatigue
occurring in a monophasic disorder like Guillain–Barré syndrome. Treatment of fatigue in neuromuscular disease starts with
symptomatic treatment of the underlying disease. When symptoms of fatigue persist, non-pharmacological interventions, such
as exercise and cognitive behavioral therapy, can be initiated. 相似文献
224.
Remco van Horssen Marieke Willemse Anna Haeger Francesca Attanasio Tuba Güneri Albrecht Schwab Christian M. Stock Roberto Buccione Jack A. M. Fransen Bé Wieringa 《Cellular and molecular life sciences : CMLS》2013,70(12):2175-2190
Oncogenic transformation involves reprogramming of cell metabolism, whereby steady-state levels of intracellular NAD+ and NADH can undergo dramatic changes while ATP concentration is generally well maintained. Altered expression of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of NAD+-salvage, accompanies the changes in NAD(H) during tumorigenesis. Here, we show by genetic and pharmacological inhibition of NAMPT in glioma cells that fluctuation in intracellular [NAD(H)] differentially affects cell growth and morphodynamics, with motility/invasion capacity showing the highest sensitivity to [NAD(H)] decrease. Extracellular supplementation of NAD+ or re-expression of NAMPT abolished the effects. The effects of NAD(H) decrease on cell motility appeared parallel coupled with diminished pyruvate-lactate conversion by lactate dehydrogenase (LDH) and with changes in intracellular and extracellular pH. The addition of lactic acid rescued and knockdown of LDH-A replicated the effects of [NAD(H)] on motility. Combined, our observations demonstrate that [NAD(H)] is an important metabolic component of cancer cell motility. Nutrient or drug-mediated modulation of NAD(H) levels may therefore represent a new option for blocking the invasive behavior of tumors. 相似文献
225.
In this paper, we present empirical and theoretical results on classification trees for randomized response data. We considered
a dichotomous sensitive response variable with the true status intentionally misclassified by the respondents using rules
prescribed by a randomized response method. We assumed that classification trees are grown using the Pearson chi-square test
as a splitting criterion, and that the randomized response data are analyzed using classification trees as if they were not
perturbed. We proved that classification trees analyzing observed randomized response data and estimated true data have a
one-to-one correspondence in terms of ranking the splitting variables. This is illustrated using two real data sets. 相似文献
226.
This research introduces a holistic framework called Design for Availability that uses the principles of Lean Sigma and Design for X to cost-effectively optimize the availability of capital goods(i.e., technical systems used in the production of end-products or -services such as medical systems, airplanes,and manufacturing equipment) throughout their entire lifetime.Manufacturers require such a framework because users of capital goods increasingly insist on high system availability levels against reduced lifetime costs.The Design for Availability framework allows manufacturers to determine the current status of system availability and associated lifetime costs,and to identify opportunities to create additional value for themselves and their customers.A case study at a global manufacturer of capital goods in the food processing industry illustrates how the framework can be used in practice and to what extent the manufacturer and customers may profit from applying Design for Availability. 相似文献
227.
228.
229.
Valentina Libri Pascal Miesen Ronald P. van Rij Amy H. Buck 《Cellular and molecular life sciences : CMLS》2013,70(19):3525-3544
MicroRNAs (miRNAs) are a ubiquitous component of gene regulatory networks that modulate the precise amounts of proteins expressed in a cell. Despite their small size, miRNA genes contain various recognition elements that enable specificity in when, where and to what extent they are expressed. The importance of precise control of miRNA expression is underscored by functional studies in model organisms and by the association between miRNA mis-expression and disease. In the last decade, identification of the pathways by which miRNAs are produced, matured and turned-over has revealed many aspects of their biogenesis that are subject to regulation. Studies in viral systems have revealed a range of mechanisms by which viruses target these pathways through viral proteins or non-coding RNAs in order to regulate cellular gene expression. In parallel, a field of study has evolved around the activation and suppression of antiviral RNA interference (RNAi) by viruses. Virus encoded suppressors of RNAi can impact miRNA biogenesis in cases where miRNA and small interfering RNA pathways converge. Here we review the literature on the mechanisms by which miRNA biogenesis and turnover are regulated in animals and the diverse strategies that viruses use to subvert or inhibit these processes. 相似文献
230.