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71.
72.
73.
Cover Picture: Selective Inhibitors of the Protein Tyrosine Phosphatase SHP2 Block Cellular Motility and Growth of Cancer Cells in vitro and in vivo (ChemMedChem 5/2015)
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74.
The tetrasaccharide 4, a substructure of ganglioside GQ1balpha, shows a remarkable affinity for the myelin-associated glycoprotein (MAG) and was therefore selected as starting point for a lead optimization program. In our search for structurally simplified and pharmacokinetically improved mimics of 4, antagonists with modifications of the core disaccharide Galbeta(1-3)GalNAc, as well as the terminal alpha(2-3)- and the internal alpha(2-6)-linked neuraminic acid were synthesized and tested in target-based binding assays. Compared to the reference tetrasaccharide 4, the most potent antagonist 17 exhibits a 360-fold improved affinity. Furthermore, pharmacokinetic parameters such as stability in the cerebrospinal fluid, logD and permeation through the BBB indicate the drug-like properties of antagonist 17. 相似文献
75.
Tatiana A. Kolesnikova Dmitry A. Gorin Paulo Fernandes Stefanie Kessel Gennady B. Khomutov Andreas Fery Dmitry G. Shchukin Helmuth Möhwald 《Advanced functional materials》2010,20(7):1189-1195
A water suspension of nanocomposite microcapsules with embedded ZnO nanoparticles in the capsule shell is reported. The microcapsule morphology is characterized by confocal microscopy, TEM, SEM, and AFM before and after ultrasound treatment. A remarkably high capsule sensitivity to ultrasound is evidenced, and it is observed to grow with increasing number of ZnO nanoparticle layers in the nanocomposite shell. This effect is correlated with the mechanical properties of microcapsules measured with AFM. 相似文献
76.
Leščić Ašler I Ivić N Kovačić F Schell S Knorr J Krauss U Wilhelm S Kojić-Prodić B Jaeger KE 《Chembiochem : a European journal of chemical biology》2010,11(15):2158-2167
Several hydrolases of the SGNH superfamily, including the lipase SrLip from Streptomyces rimosus (Q93MW7), the acyl-CoA thioesterase I TesA from Pseudomonas aeruginosa (Q9HZY8) and the two lipolytic enzymes EstA (from P. aeruginosa, O33407) and EstP (from Pseudomonas putida, Q88QS0), were examined for promiscuity. These enzymes were tested against four chemically different classes of a total of 34 substrates known to be hydrolysed by esterases, thioesterases, lipases, phospholipases, Tweenases and proteases. Furthermore, they were also analysed with respect to their amino acid sequences and structural homology, and their phylogenetic relationship was determined. The Pseudomonas esterases EstA and EstP each have an N-terminal domain with catalytic activity together with a C-terminal autotransporter domain, and so the hybrid enzymes EstA(N)-EstP(C) and EstP(N)-EstA(C) were constructed by swapping the corresponding N- and C-terminal domains, and their hydrolytic activities were compared. Interestingly, substrate specificity and kinetic measurements indicated a significant influence of the autotransporter domains on the catalytic activities of these enzymes in solution. TesA, EstA and EstP were shown to function as esterases with different affinities and catalytic efficacies towards p-nitrophenyl butyrate. Of all the enzymes tested, only SrLip revealed lipase, phospholipase, esterase, thioesterase and Tweenase activities. 相似文献
77.
Adolf Heißner Stefanie Schmidt Burkhardt von Elsner 《Journal of the science of food and agriculture》2005,85(4):539-548
Covering the soil with plastic film is an important method to modify soil temperature and improve the conditions for plant growth. For the optimal use of films in horticulture, it is necessary to quantify this effect, which depends particularly on the optical properties of the film. Five films, used mainly for soil covering in asparagus cultivation, were tested by measuring the soil temperature as well as the transmittance and reflectance in the short‐ and long‐wavelength bands: ‘Taschenfolie schwarz/weiß’, a film with black and white surfaces and pockets for fastening; ‘Antitaufolie’, a film with anti‐condensation coating, ‘Solartherm plus Folie’, a film with black top and transparent sides; ‘MaterBi Folie’, a biodegradable film; and ‘Thermoplus Folie’, a black polyethylene with transparent sides. All films were produced in Germany. The temperature measurements were carried out under controlled irradiation (short‐wavelength band) and ambient temperature conditions in the laboratory: first, 182 W m?2 and 11 °C at a depth of 0.4 m, and second, 340 W m?2 at 20 °C. A significant relationship between the temperature increase or decrease by covering the soil with the film and the calculated apparent quantities of the reflectance in the short and long‐wavelength band was derived (r2 = 0.85, n = 12). Furthermore, first tests with a physical model were carried out to obtain basic information, which should be used in the development of strategies for film management in the field. Copyright © 2004 Society of Chemical Industry 相似文献
78.
Fredi Schwägele Carmen Haschke Gerhard Krauss Karl O. Honikel 《Zeitschrift für Lebensmitteluntersuchung und -Forschung A》1996,203(1):14-20
A fast breakdown of glycogen is observed in muscles of stress-susceptible pigs leading to pale, soft and exudative (PSE) meat. We report a comparative study of pyruvate kinase from muscles of normal and PSE-prone pigs. Compared with the enzyme from normal muscle, pyruvate kinase isolated from PSE muscle shows a five times lower Michaelis constant,K
m, for phosphoenol pyruvate and a more than ten times higherk
cat/K
m value. The pH dependency of the enzymatic activity is shifted to more acidic values for pyruvate kinase from PSE muscles. According to isoelectric focusing, pyruvate kinase from PSE muscle consists of three isoforms, while only two isoforms are detectable in pyruvate kinase preparations from normal pigs. The various isoforms were isolated by preparative isoelectric focusing and their steady-state properties were compared. Isoform 3, which is found only in PSE muscle, shows a 10-fold higher specific activity, a 30-fold lowerK
m value and a 100-fold increasedk
cat/K
m value for phosphoenol pyruvate as compared to isoform 1. The presence of isoform 3 in PSE muscle appears to be responsible for the high activity of this enzyme under the more acidic conditions prevailing in PSE muscle. In vitro phosphorylation and dephosphorylation experiments using total enzyme and purified isoenzyme 1 suggest that isoforms 2 and 3 arise from isoform 1 by phosphorylation. Thus protein phosphorylation seems to be responsible for the shift in activity of pyruvate kinase, a key enzyme of glycolysis, under the acidic conditions of PSE muscles. 相似文献
79.
Marco Schwarze Stefanie Reese 《International journal for numerical methods in engineering》2011,85(3):289-329
In this paper we address the extension of a recently proposed reduced integration eight‐node solid‐shell finite element to large deformations. The element requires only one integration point within the shell plane and at least two integration points over the thickness. The possibility to choose arbitrarily many Gauss points over the shell thickness enables a realistic and efficient modeling of the non‐linear material behavior. Only one enhanced degree‐of‐freedom is needed to avoid volumetric and Poisson thickness locking. One key point of the formulation is the Taylor expansion of the inverse Jacobian matrix with respect to the element center leading to a very accurate modeling of arbitrary element shapes. The transverse shear and curvature thickness locking are cured by means of the assumed natural strain concept. Further crucial points are the Taylor expansion of the compatible cartesian strain with respect to the center of the element as well as the Taylor expansion of the second Piola–Kirchhoff stress tensor with respect to the normal through the center of the element. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
80.
Ivo Bendix Corina Schulze Clarissa von Haefen Alexandra Gellhaus Stefanie Endesfelder Rolf Heumann Ursula Felderhoff-Mueser Marco Sifringer 《International journal of molecular sciences》2012,13(10):12939-12951
Autophagy is a self-degradative process that involves turnover and recycling of cytoplasmic components in healthy and diseased tissue. Autophagy has been shown to be protective at the early stages of programmed cell death but it can also promote apoptosis under certain conditions. Earlier we demonstrated that oxygen contributes to the pathogenesis of neonatal brain damage, which can be ameliorated by intervention with recombinant human erythropoietin (rhEpo). Extrinsic- and intrinsic apoptotic pathways are involved in oxygen induced neurotoxicity but the role of autophagy in this model is unclear. We analyzed the expression of autophagy activity markers in the immature rodent brain after exposure to elevated oxygen concentrations. We observed a hyperoxia-exposure dependent regulation of autophagy-related gene (Atg) proteins Atg3, 5, 12, Beclin-1, microtubule-associated protein 1 light chain 3 (LC3), LC3A-II, and LC3B-II which are all key autophagy activity proteins. Interestingly, a single injection with rhEpo at the onset of hyperoxia counteracted these oxygen-mediated effects. Our results indicate that rhEpo generates its protective effect by modifying the key autophagy activity proteins. 相似文献