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Dr. Timo Broese Dr. Peter Ehlers Dr. Peter Langer Dr. Jan von Langermann 《Chembiochem : a European journal of chemical biology》2021,22(23):3314-3318
Fluoro-substituted and heteroaromatic compounds are valuable intermediates for a variety of applications in pharma- and agrochemistry and synthetic chemistry. This study investigates the chemoenzymatic preparation of chiral alcohols bearing a heteroaromatic ring with an increasing degree of fluorination in α-position. Starting from readily available picoline derivatives prochiral α-halogenated acyl moieties were introduced with excellent selectivity and 64–95 % yield. The formed carbonyl group was subsequently reduced to the corresponding alcohols using the alcohol dehydrogenase from Lactobacillus kefir, yielding an enantiomeric excess of 95–>99 % and up to 98 % yield. 相似文献
3.
Friederike Freiin von Hvel Ekaterini Kefalakes Claudia Grothe 《International journal of molecular sciences》2021,22(1)
Fibroblast growth factor 2 (FGF-2), ubiquitously expressed in humans and mice, is functionally involved in cell growth, migration and maturation in vitro and in vivo. Based on the same mRNA, an 18-kilo Dalton (kDa) FGF-2 isoform named FGF-2 low molecular weight (FGF-2LMW) isoform is translated in humans and rodents. Additionally, two larger isoforms weighing 21 and 22 kDa also exist, summarized as the FGF-2 high molecular weight (FGF-2HMW) isoform. Meanwhile, the human FGF-2HMW comprises a 22, 23, 24 and 34 kDa protein. Independent studies verified a specific intracellular localization, mode of action and tissue-specific spatiotemporal expression of the FGF-2 isoforms, increasing the complexity of their physiological and pathophysiological roles. In order to analyze their spectrum of effects, FGF-2LMW knock out (ko) and FGF-2HMWko mice have been generated, as well as mice specifically overexpressing either FGF-2LMW or FGF-2HMW. So far, the development and functionality of the cardiovascular system, bone formation and regeneration as well as their impact on the central nervous system including disease models of neurodegeneration, have been examined. This review provides a summary of the studies characterizing the in vivo effects modulated by the FGF-2 isoforms and, thus, offers a comprehensive overview of its actions in the aforementioned organ systems. 相似文献
4.
Dr. Raysa Khan Tareque Dr. Storm Hassell-Hart Dr. Tobias Krojer Dr. Anthony Bradley Dr. Srikannathasan Velupillai Dr. Romain Talon Dr. Michael Fairhead Dr. Iain J. Day Kamlesh Bala Dr. Robert Felix Dr. Paul D. Kemmitt Prof. Paul Brennan Prof. Frank von Delft Dr. Laura Díaz Sáez Prof. Kilian Huber Prof. John Spencer 《ChemMedChem》2020,15(24):2513-2520
Combined photochemical arylation, “nuisance effect” (SNAr) reaction sequences have been employed in the design of small arrays for immediate deployment in medium-throughput X-ray protein–ligand structure determination. Reactions were deliberately allowed to run “out of control” in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono- and bisarylations combined with SNAr processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified. 相似文献
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Dr. Vlastimil Jirasko Dr. Nils-Alexander Lakomek Dr. Susanne Penzel Dr. Marie-Laure Fogeron Prof. Dr. Ralf Bartenschlager Prof. Dr. Beat H. Meier Dr. Anja Böckmann 《Chembiochem : a European journal of chemical biology》2020,21(10):1453-1460
Proton-detected 100 kHz magic-angle-spinning (MAS) solid-state NMR is an emerging analysis method for proteins with only hundreds of microgram quantities, and thus allows structural investigation of eukaryotic membrane proteins. This is the case for the cell-free synthesized hepatitis C virus (HCV) nonstructural membrane protein 4B (NS4B). We demonstrate NS4B sample optimization using fast reconstitution schemes that enable lipid-environment screening directly by NMR. 2D spectra and relaxation properties guide the choice of the best sample preparation to record 2D 1H-detected 1H,15N and 3D 1H,13C,15N correlation experiments with linewidths and sensitivity suitable to initiate sequential assignments. Amino-acid-selectively labeled NS4B can be readily obtained using cell-free synthesis, opening the door to combinatorial labeling approaches which should enable structural studies. 相似文献
7.
The present study investigates the impact of different key solutions of mobile phones on users' effectiveness and efficiency using the devices. In the first experiment, 36 children (9 - 14 years) and in the second experiment 45 young adults (19 - 33 years) completed four common phone tasks twice consecutively on three simulated phones that had identical menus, but different key solutions. An approach was undertaken to quantify the complexity of keys in three models, incorporating different factors contributing to the keys' complexity (number of key options, number of modes and number of modes with a semantically dissimilar meaning), in order to predict users' performance decrements. As a further main factor, the degree of the users' locus of control (LOC) was measured and interactions with performance outcomes were studied. As dependent measures, the number of inefficient keystrokes, the number of tasks solved and the processing time were determined. Results showed a significant effect of control key solutions on users' efficiency and effectiveness for both children and young adults. Moreover, children's LOC values significantly interacted with performance: children with low LOC values showed the lowest performance and no learnability, especially when using keys with a high complexity. From the three factors contributing to the complexity of keys, keys exerting different functions with semantically inconsistent meanings had the worst effect on performance. It is concluded that in mobile user interface design keys with semantically inconsistent meanings should be generally avoided. 相似文献
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Test Case Generation as an AI Planning Problem 总被引:6,自引:0,他引:6
Adele E. Howe Anneliese von Mayrhauser Richard T. Mraz 《Automated Software Engineering》1997,4(1):77-106
While Artificial Intelligence techniques have been applied to a variety of software engineering applications, the area of automated software testing remains largely unexplored. Yet, test cases for certain types of systems (e.g., those with command language interfaces and transaction based systems) are similar to plans. We have exploited this similarity by constructing an automated test case generator with an AI planning system at its core. We compared the functionality and output of two systems, one based on Software Engineering techniques and the other on planning, for a real application: the StorageTek robot tape library command language. From this, we showed that AI planning is a viable technique for test case generation and that the two approaches are complementary in their capabilities. 相似文献
10.
Osvath P. Zingales G. Bartnikas R. Salama M.M.A. von Glahn P. Gulski E. Quinlan J. Steiner J.P. Stone G.C. 《Dielectrics and Electrical Insulation, IEEE Transactions on》1995,2(4):685-699
Some of the more salient aspects of the digital processing technology of PD signals are examined. Most of the efforts in this field are concentrated on the application of digital analyzers for pulse height analysis, pattern recognition and identification of the physical phenomena. It is demonstrated that errors in the signal processing unit can lead to dominant mistakes in the interpretation of the test results 相似文献