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11.
Sebastian Roth Peter Stockinger Jakob Steff Simon Steimle Dr. Viktor Sautner Prof. Dr. Kai Tittmann Prof. Dr. Jürgen Pleiss Prof. Dr. Michael Müller 《Chembiochem : a European journal of chemical biology》2020,21(18):2615-2619
The family of NAD(P)H-dependent short-chain dehydrogenases/reductases (SDRs) comprises numerous biocatalysts capable of C=O or C=C reduction. The highly homologous noroxomaritidine reductase (NR) from Narcissus sp. aff. pseudonarcissus and Zt_SDR from Zephyranthes treatiae, however, are SDRs with an extended imine substrate scope. Comparison with a similar SDR from Asparagus officinalis (Ao_SDR) exhibiting keto-reducing activity, yet negligible imine-reducing capability, and mining the Short-Chain Dehydrogenase/Reductase Engineering Database indicated that NR and Zt_SDR possess a unique active-site composition among SDRs. Adapting the active site of Ao_SDR accordingly improved its imine-reducing capability. By applying the same strategy, an unrelated SDR from Methylobacterium sp. 77 (M77_SDR) with distinct keto-reducing activity was engineered into a promiscuous enzyme with imine-reducing activity, thereby confirming that the ability to reduce imines can be rationally introduced into members of the “classical” SDR enzyme family. Thus, members of the SDR family could be a promising starting point for protein approaches to generate new imine-reducing enzymes. 相似文献
12.
Potential mGAT4 inhibitors derived from the lead substance (S)-SNAP-5114 have been synthesized and characterized for their inhibitory potency. Variations from the parent compound included the substitution of one of its aromatic 4-methoxy and 4-methoxyphenyl groups, respectively, with a more polar moiety, including a carboxylic acid, alcohol, nitrile, carboxamide, sulfonamide, aldehyde or ketone function, or amino acid partial structures. Furthermore, it was investigated how the substitution of more than one of the aromatic 4-methoxy groups affects the potency and selectivity of the resulting compounds. Among the synthesized test substances (S)-1-{2-[(4-formylphenyl)bis(4-methoxyphenyl)-methoxy]ethyl}piperidine-3-carboxylic acid, that features a carbaldehyde function in place of one of the aromatic 4-methoxy moieties of (S)-SNAP-5114, was found to have a pIC50 value of 5.89±0.07, hence constituting a slightly more potent mGAT4 inhibitor than the parent substance while showing comparable subtype selectivity. 相似文献
13.
Karim Gharbi Louise Matthews James Bron Ron Roberts Alan Tinch Michael Stear 《Journal of the Royal Society Interface》2015,12(110)
Sea lice threaten the welfare of farmed Atlantic salmon and the sustainability of fish farming across the world. Chemical treatments are the major method of control but drug resistance means that alternatives are urgently needed. Selective breeding can be a cheap and effective alternative. Here, we combine experimental trials and diagnostics to provide a practical protocol for quantifying resistance to sea lice. We then combined quantitative genetics with epidemiological modelling to make the first prediction of the response to selection, quantified in terms of reduced need for chemical treatments. We infected over 1400 young fish with Lepeophtheirus salmonis, the most important species in the Northern Hemisphere. Mechanisms of resistance were expressed early in infection. Consequently, the number of lice per fish and the ranking of families were very similar at 7 and 17 days post infection, providing a stable window for assessing susceptibility to infection. The heritability of lice numbers within this time window was moderately high at 0.3, confirming that selective breeding is viable. We combined an epidemiological model of sea lice infection and control on a salmon farm with genetic variation in susceptibility among individuals. We simulated 10 generations of selective breeding and examined the frequency of treatments needed to control infection. Our model predicted that substantially fewer chemical treatments are needed to control lice outbreaks in selected populations and chemical treatment could be unnecessary after 10 generations of selection. Selective breeding for sea lice resistance should reduce the impact of sea lice on fish health and thus substantially improve the sustainability of Atlantic salmon production. 相似文献
14.
Thin Film Thermoelectric Metal–Organic Framework with High Seebeck Coefficient and Low Thermal Conductivity 下载免费PDF全文
15.
Digital technology becomes more powerful, intelligent, pervasive and ubiquitous. Ethical aspects of this development have not yet drawn the appropriate attention of researchers and engineers. This paper presents an instrument that aims at measuring the individual ethical position with regard to the design and development of computer software. The development of the Epos tool was based on two data collections. The data of the first survey (n1 = 147 participants) were used to select items and to determine the factorial structure of the questionnaire. Results show that the Epos instrument reliably assesses peoples’ ethical opinion with respect to five central components: (1) regulation, (2) data privacy, (3) domain specific knowledge, (4) societal responsibility and (5) company responsibility. In the second survey, we determined the stability of the instruments factor structure by assessing a sample of n2?=?196 participants. A confirmatory factor analysis (CFA) supported the initial factor structure. Next steps and further implications are discussed regarding the final version of the questionnaire. 相似文献
16.
Lingfeng Zhou Zhipeng Zeng Michael P. Brady Donovan N. Leonard Harry M. Meyer Yukinori Yamamoto Wenyuan Li Greg Collins Xingbo Liu 《International Journal of Hydrogen Energy》2021,46(41):21619-21633
The chromium (Cr) evaporation behavior of several different types of iron (Fe)-based AFA alloys and benchmark Cr2O3-forming Fe-based 310 and Ni-based 625 alloys was investigated for 500 h exposures at 800 °C to 900 °C in air with 10% H2O. The Cr evaporation rates from alumina-forming austenitic (AFA) alloys were ~5 to 35 times lower than that of the Cr2O3-forming alloys depending on alloy and temperature. The Cr evaporation behavior was correlated with extensive characterization of the chemistry and microstructure of the oxide scales, which also revealed a degree of quartz tube Si contamination during the test. Long-term oxidation kinetics were also assessed at 800 to 1000 °C for up to 10,000 h in air with 10% H2O to provide further guidance for SOFC BOP component alloy selection. 相似文献
17.
In this paper, we first re-examine the previous protocol of controlled quantum secure direct communication of Zhang et al.’s scheme, which was found insecure under two kinds of attacks, fake entangled particles attack and disentanglement attack. Then, by changing the party of the preparation of cluster states and using unitary operations, we present an improved protocol which can avoid these two kinds of attacks. Moreover, the protocol is proposed using the three-qubit partially entangled set of states. It is more efficient by only using three particles rather than four or even more to transmit one bit secret information. Given our using state is much easier to prepare for multiqubit states and our protocol needs less measurement resource, it makes this protocol more convenient from an applied point of view. 相似文献
18.
19.
A Stimulation Method to Assess the Contractile Status of the Lumbar Extensors in a Seated Posture 下载免费PDF全文
The purpose of present study was to develop and evaluate methods to assess stimulation responses of the lumbar extensors, as part of a longer‐term goal of detecting fatigue during prolonged sitting. Three stimulation frequencies (2, 5, and 8 Hz) were tested in separate stages, which include 3 stimulation trains and 4 sampling blocks. Repeated measures analyses of variance were used to determine whether any significant differences in mean stimulation responses occurred with respect to stimulation frequency, sampling block, and stimulation train. Reliability of measured stimulation responses was assessed within and between sampling blocks using intraclass correlation coefficients. Stimulation frequencies significantly affected the stimulation responses and time‐to‐potentiation differed between the 3 stimulation frequencies; it was highest for 2 Hz stimulation. All 3 stimulation frequencies resulted in excellent reliability within and between sampling blocks. Use of the current protocol at 2 Hz is recommended as appropriate to measure the lumbar extensors status during prolonged sitting. 相似文献
20.
Dr. Yahu A. Liu Dr. Qihui Jin Qiang Ding Dr. Xueshi Hao Tingting Mo Shanshan Yan Dr. Yefen Zou Dr. Zhihong Huang Xiaoyue Zhang Wenqi Gao Dr. Tom Y.-H. Wu Chun Li Dr. Badry Bursalaya Dr. Michael Di Donato Dr. You-Qing Zhang Lisa Deaton Dr. Weijun Shen Dr. Brandon Taylor Anwesh Kamireddy Dr. George Harb Dr. Jing Li Dr. Yong Jia Dr. Andrew M. Schumacher Dr. Bryan Laffitte Dr. Richard Glynne Dr. Shifeng Pan Dr. Peter McNamara Dr. Valentina Molteni Dr. Jon Loren 《ChemMedChem》2020,15(16):1562-1570
Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation. 相似文献