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21.
Tyk2 belongs to the Janus kinase (JAK) family of receptor associated tyrosine kinases, characterized by a large N-terminal region, a kinase-like domain and a tyrosine kinase domain. It was previously shown that Tyk2 contributes to interferon-alpha (IFN-alpha) signaling not only catalytically, but also as an essential intracellular component of the receptor complex, being required for high affinity binding of IFN-alpha. For this function the tyrosine kinase domain was found to be dispensable. Here, it is shown that mutant cells lacking Tyk2 have significantly reduced IFN-alpha receptor 1 (IFNAR1) protein level, whereas the mRNA level is unaltered. Expression of the N-terminal region of Tyk2 in these cells reconstituted wild-type IFNAR1 level, but did not restore the binding activity of the receptor. Studies of mutant Tyk2 forms deleted at the N terminus indicated that the integrity of the N-terminal region is required to sustain IFNAR1. These studies also showed that the N-terminal region does not directly modulate the basal autophosphorylation activity of Tyk2, but it is required for efficient in vitro IFNAR1 phosphorylation and for rendering the enzyme activatable by IFN-alpha. Overall, these results indicate that distinct Tyk2 domains provide different functions to the receptor complex: the N-terminal region sustains IFNAR1 level, whereas the kinase-like domain provides a function toward high affinity ligand binding.  相似文献   
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To define conditions promoting inherited infection by Lyme disease spirochetes in Ixodes ticks, we variously infected ticks with Borrelia afzelii and examined their progenies by dark-field microscopy, immunofluorescence, PCR, and serial passage. No episode of inherited infection was evident, regardless of instar or gender infected or frequency of exposure. We suggest that these spirochetes rarely, if ever, are inherited by vector ticks.  相似文献   
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The Journal of Supercomputing - Scientific application codes are often long-running time- and energy-consuming parallel codes, and the tuning of these methods towards the characteristics of a...  相似文献   
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Zusammenfassung Es werden pharmakokinetische Modelle angegeben, um den Konzentrationsverlauf von Arzneimittelrückständen im Menschen zu berechnen, die mit der Nahrung aufgenommen werden. Dabei lassen sich zwei Kompartimentmodelle für die Kinetik in der Nahrung und im Menschen koppeln: Das erste System liefert die Anfangswerte (bzw. eine Folge von Anfangswerten) für das zweite System. Das Modell wird auf die Übertragung von Chloramphenicol durch Speisefische auf den Menschen und auf die Übertragung von Theophyin durch die Muttermilch auf gestillte Säuglinge angewendet. Durch Einführung einer günstigsten und ungünstigsten Parameterkombination werden Grenzverläufe für die Blutspiegel berechnet, die als Grundlage einer Rückstandsbewertung dienen können.
Residues of active substances following the consumption of contaminated food —Status report on the evaluation of residues based on two drugs
Summary Pharmacokinetic models are presented for the computation of time courses of blood levels of drugs in man following the consumption of contaminated food. Mathematically, two linear systems of differential equations are set up for the donor organism (e.g., trout) and for the recipient, (e.g., man), where the first system generates the initial conditions for the second. Models of this kind are applied to the transfer of chloramphenicol to man via carp and trout (which had previously been administered this drug) and to the transfer of theophylline to infants via breast milk. Limiting concentration profiles are computed by constructing the most favourable and most adverse combinations of parameters with respect to drug elimination in both the donor and recipient organism.
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Brillouin scattering (BS), photon correlation spectroscopy (PCS), and ultrasonic (US) measurements were conducted to study the curing process of diglycidyl ether of bisphenol A with butane-1,4-diol at a curing temperature of 100°C. The experimental techniques probe the primary glass-rubber transition during the curing reaction. The primary relaxation time τ obtained from the BS and US velocity and absorption increases with curing time and hence the BS experiment measures τ at earlier stages of cure than the US experiment. The relaxation times at a different extent of reaction and for different measuring temperatures are consistent with BS, US, PCS, and DSC measurements and conform to a single reduced Vogel–Fulcher–Hesse–Tamann equation. Furthermore, the US experiments show evidence of secondary relaxations in the epoxy system.  相似文献   
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Different polyurethanes were synthesized by varying the diol as well as the diisocyanate components and chain extenders. Polyurethanes with OH-groups were obtained by photo- and thermoinitiation of the radical polymerization of hydroxy alkyl acrylates in the presence of the polyurethanes. The polymers were evaluated with respect to their biocompatibility by measuring the cell spreading, the rates of DNA- and protein synthesis and the swelling behaviour. The differences in the surfaces and the bulks between the selected basic polyurethane and the functionalized modification were determined and characterized by XPS, FTIR-ATR and 13C-FT-NMR-spectroscopy. The mechanical data of Tecoflex EG 60D® and Pellethane 2363–80AE® were compared with the data of the synthesized polyurethanes.  相似文献   
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The characterization of thin, selectively imprinted films of nylon‐6 was performed. Amino acids were used as template molecules. Spin‐cast films were prepared with sizes ranging from 2 μm to 300 nm, depending on the nylon and template concentration in the casting solution. The morphological characteristics of the film surface were examined by atomic force microscopy, and the structure within the films was observed by freeze‐fracture scanning electron microscopy. The film activity was clearly coordinated with the appearance of nanometer‐sized pores both on the surface and within the film. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 2919–2926, 2006  相似文献   
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The exponential growth of Internet during the last decade leads us to make more efforts in the researching and developing of sustainable Web servers in order to decrease the global energy demand. In this paper, we cover, as a first step, a proper review of the literature related to the energy efficiency research in Web server systems to depict the state of the art to plan further contributions as more research in sustainable Web systems. We also propose and implement an energy metric that permits to establish a relation between the Quality of Service (QoS) obtained by the system and the power it consumes.  相似文献   
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