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51.
Werten Marc W. T.; Wisselink Wouter H.; Jansen-van den Bosch Tanja J.; de Bruin Eric C.; de Wolf Frits A. 《Protein engineering, design & selection : PEDS》2001,14(6):447-454
A custom-designed, highly hydrophilic gelatin was produced in
Pichia pastoris
. Secreted production levels in single-copytransformants were in the range 36 g/l of clarified brothand purification to near homogeneity could be accomplished bydifferential ammonium sulfate precipitation. Despite the factthat gelatins are highly susceptible to proteolysis becauseof their unfolded structure, the recombinant protein was shownto be fully intact by SDSPAGE, N-terminal sequencing,gel filtration chromatography and mass spectrometry. Owing toits highly hydrophilic nature, the migration of the syntheticgelatin in SDSPAGE was severely delayed. Esterificationof the carboxylic amino acid side chains resulted in normalmigration. The high polarity of the synthetic gelatin also accountsfor its negligible surface activity in water at concentrationsup to 5% (w/v), as determined by tensiometry. Circular dichroismspectrometry showed that the non-hydroxylated gelatin did notform triple helices at 4°C. The spectrum was even more representativeof the random coil conformation than the spectrum of naturalnon-hydroxylated gelatins. 相似文献
52.
Alexander Paasche Markus Schiller Dr. Tanja Schirmeister Prof. Dr. Bernd Engels Prof. Dr. 《ChemMedChem》2010,5(6):869-880
We investigated the reactions between substituted α,β‐unsaturated carbonyl compounds (Michael systems) and thiols by computations as well as chemoassays. The results give insight into variations in the underlying mechanisms as a function of the substitution pattern. This is of interest for the mechanisms of inhibition of the SARS coronavirus main protease (SARS‐CoV Mpro) by etacrynic acid derivatives as well as for the excess toxicity of substituted α,β‐unsaturated carbonyl compounds. This study compares possible reaction courses including 1,4‐addition followed by a ketonization step, and underscores the importance of a base‐catalyzed step for the reactivity of thiol groups in enzymes. Phenyl and methyl substituents at the Michael system decrease the reactivity of the electrophilic compound, but chlorophenyl substituents partly recover the reactivity. Computations also indicate that electron‐pushing substituents lead to a change in the reaction mechanism. The conformation of the Michael system is also found to significantly influence reactivity: the s‐cis conformation leads to higher reactivity than the s‐trans conformation. The computed data explain the trends in measured inhibition potencies of substituted α,β‐unsaturated carbonyl compounds and of reaction rates in chemical assays. They also indicate that the reversibility of inhibition does not stand in contrast to the formation of a new covalent bond between inhibitor and protease. 相似文献
53.
Stefan Strobl Peter Supancic Tanja Lube Robert Danzer 《Journal of the European Ceramic Society》2012,32(8):1491-1501
The Newman and Raju formula for the stress intensity factor of a semi-elliptical surface crack loaded in uniaxial tension or in bending has been developed about 30 years ago using an FE-analysis for several geometric parameters and fitting an empirical equation to the data points. The Poisson's ratio analyzed was 0.3.In this paper a reassessment of the Newman and Raju formula is made, where all relevant geometric parameters of crack and specimen and the Poisson's ratio are considered. The deviations of the old formula from the new results are up to 21%, if the full range of Poisson's ratio is taken into account. Furthermore the influence of the crack-surface intersection angle is discussed.The results of this work are important for more precise fracture toughness measurements in brittle materials and give a practical guidance for appropriate specimen preparation for fracture toughness measurements, which is also considered here. 相似文献
54.
Tanja Zseby Joachim Fabini Dipika Rani 《e & i Elektrotechnik und Informationstechnik》2014,131(1):8-13
Synchronized phasor measurements provide the basis for fine-grained wide area power quality monitoring in electric grids. Time-synchronized phasor measurement units (PMUs) are deployed at different locations in the grid and report 10–60 measurements/second to energy management systems or other applications. For control applications it is crucial to receive measurement data as soon as possible after a state change in order to trigger corrective actions in time to prevent incidents in the grid. In this paper we analyze characteristics of synchrophasor M2M communication for different network technologies, including VDSL, HSPA and LTE networks. We briefly review synchrophasor communication approaches and real-time demands. We then emulate PMU traffic and perform measurements on different networks. We show how the underlying technology influences one-way delay patterns for synchrophasor communication, which has direct implication on the achievable real-time properties. 相似文献
55.
Contemporary urban policies in various liberal democracies are purposefully crafted to foster both economic efficiency and social justice. For Barel (1989), achieving these directives constitutes a ‘paradox’. Yet, as argued here, this paradox is not new. Rather, it is rooted in liberalism, which, in turn, shapes mainstream planning practices and modes of government. This paper therefore turns to the ‘ethico-politics’ of planning in order to demonstrate how the City of Johannesburg articulates its economic growth and social responsibility policies. It is proposed that unless planners challenge the often unquestioned liberal norms of planning, entrenched norms will continue to obscure alternative possibilities. 相似文献
56.
57.
Tanja E. J. Vos Felix F. Lindlar Benjamin Wilmes Andreas Windisch Arthur I. Baars Peter M. Kruse Hamilton Gross Joachim Wegener 《Software Quality Journal》2013,21(2):259-288
During the past years, evolutionary testing research has reported encouraging results for automated functional (i.e. black-box) testing. However, despite promising results, these techniques have hardly been applied to complex, real-world systems and as such, little is known about their scalability, applicability, and acceptability in industry. In this paper, we describe the empirical setup used to study the use of evolutionary functional testing in industry through two case studies, drawn from serial production development environments at Daimler and Berner & Mattner Systemtechnik, respectively. Results of the case studies are presented, and research questions are assessed based on them. In summary, the results indicate that evolutionary functional testing in an industrial setting is both scalable and applicable. However, the creation of fitness functions is time-consuming. Although in some cases, this is compensated by the results, it is still a significant factor preventing functional evolutionary testing from more widespread use in industry. 相似文献
58.
59.
Lipids encompass a myriad of natural compounds with many essential biological functions and applications across the areas of food and nutrition, health and medicine, and modern nanotechnologies. Arsenic has long been known as a highly toxic element. What happens when the two come together? 相似文献
60.
Synthesis and Biological Evaluation of Papain‐Family Cathepsin L‐Like Cysteine Protease Inhibitors Containing a 1,4‐Benzodiazepine Scaffold as Antiprotozoal Agents 下载免费PDF全文
Dr. Roberta Ettari Dr. Andrea Pinto Dr. Lucia Tamborini Dr. Ilenia C. Angelo Prof. Silvana Grasso Prof. Maria Zappalà Dr. Natale Capodicasa Dr. Laura Yzeiraj Dr. Esther Gruber Dr. Makoah N. Aminake Dr. Gabriele Pradel Prof. Tanja Schirmeister Prof. Carlo De Micheli Prof. Paola Conti 《ChemMedChem》2014,9(8):1817-1825
Novel papain‐family cathepsin L‐like cysteine protease inhibitors endowed with antitrypanosomal and antimalarial activity were developed, through an optimization study of previously developed inhibitors. In the present work, we studied the structure–activity relationships of these derivatives, with the aim to develop new analogues with a simplified and more synthetically accessible structure and with improved antiparasitic activity. The structure of the model compounds was significantly simplified by modifying or even eliminating the side chain appended at the C3 atom of the benzodiazepine scaffold. In addition, a simple methylene spacer of appropriate length was inserted between the benzodiazepine ring and the 3‐bromoisoxazoline moiety. Several rhodesain and falcipain‐2 inhibitors displaying single‐digit micromolar or sub‐micromolar antiparasitic activity against one or both parasites were identified, with activities that were one order of magnitude more potent than the model compounds. 相似文献