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1.
Katja F. Hellendahl Felix Kaspar Dr. Xinrui Zhou Zhaoyi Yang Prof. Dr. Zhen Huang Prof. Dr. Peter Neubauer Dr. Anke Kurreck 《Chembiochem : a European journal of chemical biology》2021,22(11):2002-2009
Selenium-modified nucleosides are powerful tools to study the structure and function of nucleic acids and their protein interactions. The widespread application of 2-selenopyrimidine nucleosides is currently limited by low yields in established synthetic routes. Herein, we describe the optimization of the synthesis of 2-Se-uridine and 2-Se-thymidine derivatives by thermostable nucleoside phosphorylases in transglycosylation reactions using natural uridine or thymidine as sugar donors. Reactions were performed at 60 or 80 °C and at pH 9 under hypoxic conditions to improve the solubility and stability of the 2-Se-nucleobases in aqueous media. To optimize the conversion, the reaction equilibria in analytical transglycosylation reactions were studied. The equilibrium constants of phosphorolysis of the 2-Se-pyrimidines were between 5 and 10, and therefore differ by an order of magnitude from the equilibrium constants of any other known case. Hence, the thermodynamic properties of the target nucleosides are inherently unfavorable, and this complicates their synthesis significantly. A tenfold excess of sugar donor was needed to achieve 40−48 % conversion to the target nucleoside. Scale-up of the optimized conditions provided four Se-containing nucleosides in 6–40 % isolated yield, which compares favorably to established chemical routes. 相似文献
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Reading requires the orchestration of visual, attentional, language-related, and oculomotor processing constraints. This study replicates previous effects of frequency, predictability, and length of fixated words on fixation durations in natural reading and demonstrates new effects of these variables related to 144 sentences. Such evidence for distributed processing of words across fixation durations challenges psycholinguistic immediacy-of-processing and eye-mind assumptions. Most of the time the mind processes several words in parallel at different perceptual and cognitive levels. Eye movements can help to unravel these processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
4.
Gotlib Ian H.; Krasnoperova Elena; Yue Dana Neubauer; Joormann Jutta 《Canadian Metallurgical Quarterly》2004,113(1):127
An information-processing paradigm was used to examine attentional biases in clinically depressed participants, participants with generalized anxiety disorder (GAD), and nonpsychiatric control participants for faces expressing sadness, anger, and happiness. Faces were presented for 1,000 ms, at which point depressed participants had directed their attention selectively to depression-relevant (i.e., sad) faces. This attentional bias was specific to the emotion of sadness; the depressed participants did not exhibit attentional biases to the angry or happy faces. This bias was also specific to depression; at 1,000 ms, participants with GAD were not attending selectively to sad, happy, or anxiety-relevant (i.e., angry) faces. Implications of these findings for both the cognitive and the interpersonal functioning of depressed individuals are discussed and directions for future research are advanced. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
5.
R. Breil T. Fries J. Garnaes J. Haycocks D. Hüser J. Joergensen W. Kautek L. Koenders N. Kofod K. R. Koops R. Korntner B. Lindner W. Mirand A. Neubauer J. Peltonen G. B. Picotto M. Pisani H. Rothe M. Sahre M. Stedman G. Wilkening 《Precision Engineering》2002,26(3)
Comparison measurements on reference standards are reported in which 13 partners with different instruments took part. A set of prototype standards which had been produced and calibrated within a European project were used for the measurements. Here, results of measurements on a 240 nm step height standard and a two-dimensional lateral standard with a nominal pitch of 1 μm are reported. 相似文献
6.
A. Neubauer 《Computing》1987,39(1):43-55
We discuss the numerical realization of an a-posteriori parameter choice for Tikhonov regularization of linear integral equations of the first kind in Hilbert scales that leads to optimal convergence rates and that does not need any information about the exact solution. Numerical examples confirm the theoretical results. 相似文献
7.
W. Fallmann P. Hudek I. Kostic A. Neubauer D. Pum I. Rangelow K. Riedling F. Rüdenauer U. B. Sleytr G. Stangl 《e & i Elektrotechnik und Informationstechnik》1998,115(7-8):349-353
This contribution describes the preparation, based upon a chemically amplified novolak resist (CAR), electron beam lithography, and ECR plasma etching, of structures with a high aspect ratio (10∶1) and lateral dimensions in the sub-micrometer range (150nm–300nm) which may serve as collector surfaces for sub-μm dust particles in a space experiment. 相似文献
8.
M Kaefer JE Audia N Bruchovsky RL Goode KC Hsiao IY Leibovitch JH Krushinski C Lee CP Steidle DM Sutkowski BL Neubauer 《Canadian Metallurgical Quarterly》1996,58(2):195-205
Each amino acid is represented by a vector of numerical measurements for the attributes of volume, area, hydrophilicity, polarity, hydrogen bonding, shape, and charge. Inter-residue distances are then calculated according to common metrics, and we introduce a new clustering objective function derived from information-theoretic considerations. The arguments of the function are the inter-object distances of the things to be clustered: in this case the amino acids. By means of approximating the solution of an integer programming problem, then, the residues are partitioned into clusters. The clusters obtained are compared with groups obtained in substitution/mutation studies and found to be similar. Thus, probably the strongest and most objective evidence to date is supplied for believing that physico-chemical properties account for the viability of substitutions and that the important similarities/differences are explained by a relatively small and simple set of properties. 相似文献
9.
NJ Watkins A Gottschalk G Neubauer B Kastner P Fabrizio M Mann R Lührmann 《Canadian Metallurgical Quarterly》1998,4(12):1549-1568
The eukaryotic nucleolus contains a large number of small nucleolar RNAs (snoRNAs) that are involved in preribosomal RNA (pre-rRNA) processing. The H box/ACA-motif (H/ACA) class of snoRNAs has recently been demonstrated to function as guide RNAs targeting specific uridines in the pre-rRNA for pseudouridine (psi) synthesis. To characterize the protein components of this class of snoRNPs, we have purified the snR42 and snR30 snoRNP complexes by anti-m3G-immunoaffinity and Mono-Q chromatography of Saccharomyces cerevisiae extracts. Sequence analysis of the individual polypeptides demonstrated that the three proteins Gar1p, Nhp2p, and Cbf5p are common to both the snR30 and snR42 complexes. Nhp2p is a highly basic protein that belongs to a family of putative RNA-binding proteins. Cbf5p has recently been demonstrated to be involved in ribosome biogenesis and also shows striking homology with known prokaryotic psi synthases. The presence of Cbf5p, a putative psi synthase in each H/ACA snoRNP suggests that this class of RNPs functions as individual modification enzymes. Immunoprecipitation studies using either anti-Cbf5p antibodies or a hemagglutinin-tagged Nhp2p demonstrated that both proteins are associated with all H/ACA-motif snoRNPs. In vivo depletion of Nhp2p results in a reduction in the steady-state levels of all H/ACA snoRNAs. Electron microscopy of purified snR42 and snR30 particles revealed that these two snoRNPs possess a similar bipartite structure that we propose to be a major structural determining principle for all H/ACA snoRNPs. 相似文献
10.
Nadine Kretschmer Antje Hufner Christin Durchschein Katrin Popodi Beate Rinner Birgit Lohberger Rudolf Bauer 《International journal of molecular sciences》2021,22(5)
Melanoma is the deadliest form of skin cancer and accounts for about three quarters of all skin cancer deaths. Especially at an advanced stage, its treatment is challenging, and survival rates are very low. In previous studies, we showed that the constituents of the roots of Onosma paniculata as well as a synthetic derivative of the most active constituent showed promising results in metastatic melanoma cell lines. In the current study, we address the question whether we can generate further derivatives with optimized activity by synthesis. Therefore, we prepared 31, mainly novel shikonin derivatives and screened them in different melanoma cell lines (WM9, WM164, and MUG-Mel2 cells) using the XTT viability assay. We identified (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl 2-cyclopropyl-2-oxoacetate as a novel derivative with even higher activity. Furthermore, pharmacological investigations including the ApoToxGloTM Triplex assay, LDH assay, and cell cycle measurements revealed that this compound induced apoptosis and reduced cells in the G1 phase accompanied by an increase of cells in the G2/M phase. Moreover, it showed hardly any effects on the cell membrane integrity. However, it also exhibited cytotoxicity against non-tumorigenic cells. Nevertheless, in summary, we could show that shikonin derivatives might be promising drug leads in the treatment of melanoma. 相似文献