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M. Sc. Yasemin Akbulut Hannah J. Gaunt Prof. Katsuhiko Muraki Dr. Melanie J. Ludlow Dr. Mohamed S. Amer Dr. Alexander Bruns Dr. Naveen S. Vasudev Dr. Lea Radtke Dr. Matthieu Willot M. Sc. Sven Hahn M. Sc. Tobias Seitz Dr. Slava Ziegler Prof. Dr. Mathias Christmann Prof. Dr. David J. Beech Prof. Dr. Herbert Waldmann 《Angewandte Chemie (International ed. in English)》2015,54(12):3787-3791
Current therapies for common types of cancer such as renal cell cancer are often ineffective and unspecific, and novel pharmacological targets and approaches are in high demand. Here we show the unexpected possibility for the rapid and selective killing of renal cancer cells through activation of calcium‐permeable nonselective transient receptor potential canonical (TRPC) calcium channels by the sesquiterpene (?)‐englerin A. This compound was found to be a highly efficient, fast‐acting, potent, selective, and direct stimulator of TRPC4 and TRPC5 channels. TRPC4/5 activation through a high‐affinity extracellular (?)‐englerin A binding site may open up novel opportunities for drug discovery aimed at renal cancer. 相似文献
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Tanya Zelevinsky Dr. Sebastian Blatt Martin M. Boyd Dr. Gretchen K. Campbell Dr. Andrew D. Ludlow Jun Ye Prof. 《Chemphyschem》2008,9(3):375-382
Cooling and trapping of neutral atoms using laser techniques has enabled extensive progress in precise, coherent spectroscopy. In particular, trapping ultracold atoms in optical lattices in a tight confinement regime allows us to perform high‐resolution spectroscopy unaffected by atomic motion. We report on the recent developments of optical lattice atomic clocks that have led to optical spectroscopy coherent at the one second timescale. The lattice clock techniques also open a promising pathway toward trapped ultracold molecules and the possible precision measurement opportunities such molecules offer. 相似文献
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This study examined whether vocal fold kinematics prior to phonation differed between hard (glottal), normal, or breathy onsets in men and women. Glottal landmarks were identified and digitized from videotape recorded with a rigid laryngoscope during different voice onset types. Significant linear relationships (p 0.0055) were found among onset types on measures of (a) gesture duration when moving from 80% to 20% of maximum distance during adduction, (b) maximum velocity, (c) duration between the completion of adduction and phonation onset, and (d) ratios of maximum velocity to maximum distance between the vocal processes, an estimate of stiffness. The gesture duration was greatest for breathy onsets and least for hard onsets, while the maximum velocity, latency between adduction and phonation onset, and estimated stiffness were greatest for hard onsets and least for breathy onsets. The results suggest that one trajectory seems to be used with increases in gesture duration being accompanied by decreases in articulator stiffness when moving from hard to normal to breathy voice onset types. 相似文献
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Gareth AD Hardy Nesrina Imami Mark R Nelson Ann K Sullivan Ron Moss Marlén MI Aasa-Chapman Brian Gazzard Frances M Gotch 《Journal of immune based therapies and vaccines》2007,5(1):6-12
Background
Fully functional HIV-1-specific CD8 and CD4 effector T-cell responses are vital to the containment of viral activity and disease progression. These responses are lacking in HIV-1-infected patients with progressive disease. We attempted to augment fully functional HIV-1-specific CD8 and CD4 effector T-cell responses in patients with advanced chronic HIV-1 infection. 相似文献9.
Carl Mayer Clinton Ludlow Green Werner Trueb Peter Christian Wlchli Conrad Hans Eugster 《Helvetica chimica acta》1978,61(2):905-921
Degradation of palustrin to (?)-dihydropalustramic acid ((2R,6S,1′S)-[6-(1′-hydroxypropyl)-2-piperidyl]acetic acid), and the structure of palustrin and palustridin The structure of the macrocyclic alkaloid palustrin is shown to be 1a . Its piperidine unit can be obtained as (?)-dihydropalustramic acid ( 6a ) by the following sequence of degradation reactions (Scheme 1): catalytic hydrogenation of 1a followed by methylation and Hofmann degradation provides the allyl base 4 . the regioselectivity of the Hofmann elimination is explained by intramolecular proton abstraction at C(3) by C(18)-O?. Catalytic reduction of 4 and subsequent acidic hydrolysis yielded 6a and N, N-dimethylputrescine (?N,N-dimethyl-1,4-butanediamine; 7 ). Loss of the N-alkyl group in the formation of 6a occurs during the catalytic hydrogenation step. This interpretation is supported by the results of model experiments. The position of the double bond in 1a is deduced from the IR. spectrum of the bromo-δ-lactone 19 prepared by treatment of 1a with N-bromosuccinimide at pH 4 (Scheme 3). Some of our previously published results on the degradation of dihydropalustrin ( 2a ) are obviously at variance with the newly proposed structure for palustrin ( 1a ). They can easily be explained by assuming a partial hydrogenolysis of the C(17)-N(1) bond during the preparation of dihydropalustrin from palustrin. Periodate cleavage of dihydropalustramic acid methyl ester ( 6b ) liberates propionaldehyde, which can be trapped by working at pH 7.5 (Scheme 2); at lower pH values it condenses rapidly with the simultaneously generated 3,4,5,6-tetrahydropyridine derivative 15 . The structure of the condensation product is proposed to be 16 on the basis of the isolation of its hydrogenation product, an isomeric dihydropalustramic acid ( 17 ). 相似文献
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David K. Ludlow Peter A. Clarkson & Andrew P. Bassom 《Studies in Applied Mathematics》1999,103(3):183-240
We study similarity reductions and exact solutions of the (2+1)-dimensional incompressible Navier–Stokes equations using the direct method originally developed by Clarkson and Kruskal [37]. The Navier–Stokes equations are reduced to their conventional stream function form, and it is shown that there exist essentially five reductions into lower-order partial differential equations. Furthermore, we study the possibilities for reducing each of these five forms to ordinary differential equations, some of which can be solved analytically, while others necessitate numerical treatment. In particular we exhibit several new reductions that are not obtained using the classical Lie group method of infinitesimal transformations, and thus we generate new exact solutions of the governing equations. Some of our solutions admit physical interpretations, and many of them contain well-known Navier–Stokes solutions as special examples. 相似文献