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1.
Dr. Lei Wang Louis P. Riel Dr. Bekim Bajrami Prof. Dr. Bin Deng Prof. Dr. Amy R. Howell Prof. Dr. Xudong Yao 《Chembiochem : a European journal of chemical biology》2021,22(3):505-515
The utilities of an α-methylene-β-lactone (MeLac) moiety as a warhead composed of multiple electrophilic sites are reported. We demonstrate that a MeLac-alkyne not only reacts with diverse proteins as a broadly reactive measurement probe, but also recruits reduced endogenous glutathione (GSH) to assemble a selective chemical probe of GSH-β-lactone (GSH-Lac)-alkyne in live cells. Tandem mass spectrometry reveals that MeLac reacts with nucleophilic cysteine, serine, lysine, threonine, and tyrosine residues, through either Michael or acyl addition. A peptide-centric proteomics platform demonstrates that the proteomic selectivity profiles of orlistat and parthenolide, which have distinct reactivities, are measurable by MeLac-alkyne as a high-coverage probe. The GSH-Lac-alkyne selectively probes the glutathione S-transferase P responsible for multidrug resistance. The assembly of the GSH-Lac probe exemplifies a modular and scalable route to develop selective probes with different recognizing moieties. 相似文献
2.
AI & SOCIETY - This paper is addressed to recent theoretical discussions of the Anthropocene, in particular Bernard Stiegler’s Neganthropocene (Open Universities Press, 2018), which... 相似文献
3.
Maarten Sijm Julianna Siciliano de Araújo Alba Ramos Llorca Dr. Kristina Orrling Lydia Stiny An Matheeussen Prof. Dr. Louis Maes Prof. Dr. Iwan J. P. de Esch Dr. Maria de Nazaré Correia Soeiro Dr. Geert Jan Sterk Prof. Dr. Rob Leurs 《ChemMedChem》2019,14(18):1662-1668
Chagas disease is becoming a worldwide problem; it is currently estimated that over six million people are infected. The two drugs in current use, benznidazole and nifurtimox, require long treatment regimens, show limited efficacy in the chronic phase of infection, and are known to cause adverse effects. Phenotypic screening of an in-house library led to the identification of 2,2′-methylenebis(5-(4-bromophenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one), a phenyldihydropyrazolone dimer, which shows an in vitro pIC50 value of 5.4 against Trypanosoma cruzi. Initial optimization was done by varying substituents of the phenyl ring, after which attempts were made to replace the phenyl ring. Finally, the linker between the dimer units was varied, ultimately leading to 2,2′-methylenebis(5-(3-bromo-4-methoxyphenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one (NPD-0228) as the most potent analogue. NPD-0228 has an in vitro pIC50 value of 6.4 against intracellular amastigotes of T. cruzi and no apparent toxicity against the human MRC-5 cell line and murine cardiac cells. 相似文献
4.
Brittleness is an important parameter controlling the mechanical behavior and failure characteristics of rocks under loading and unloading conditions,such as fracability,cutability,drillability and rockburst proneness.As such,it is of high practical value to correctly evaluate rock brittleness.However,the definition and measurement method of rock brittleness have been very diverse and not yet been standardized.In this paper,the definitions of rock brittleness are firstly reviewed,and several representative definitions of rock brittleness are identified and briefly discussed.The development and role of rock brittleness in different fields of rock engineering are also studied.Eighty brittleness indices publicly available in rock mechanics literature are compiled,and the measurement method,applicability and limitations of some indices are discussed.The results show that(1)the large number of brittleness indices and brittleness definitions is attributed to the different foci on the rock behavior when it breaks;(2)indices developed in one field usually are not directly applicable to other fields;and(3)the term“brittleness”is sometimes misused,and many empirically-obtained brittleness indices,which lack theoretical basis,fail to truly reflect rock brittleness.On the basis of this review,three measurement methods are identified,i.e.(1)elastic deformation before fracture,(2)shape of post-peak stressestrain curves,and(3)methods based on fracture mechanics theory,which have the potential to be further refined and unified to become the standard measurement methods of rock brittleness.It is highly beneficial for the rock mechanics community to develop a robust definition of rock brittleness.This study will undoubtedly provide a comprehensive timely reference for selecting an appropriate brittleness index for their applications,and will also pave the way for the development of a standard definition and measurement method of rock brittleness in the long term. 相似文献
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6.
Boundary colors are observed when light from a scene is dispersed by a prism or diffraction grating. We discovered that patterns with repeating black and white stripes can produce repeating bands of boundary colors with two hues. These hues are virtually constant as measured by chromaticity or CIELAB. We found seven cases of this kind using a new appearance model for boundary colors. The model correctly predicts that green and magenta bands recur as stripe widths and dispersion strength vary. The first green/magenta case in the sequence traces out an accurate ellipse in XYZ color space. Green and magenta bands are prominent in supernumerary rainbows and interference rings, and we explain why that might be the case. The explanation is based on an interesting property of the visible spectrum. In addition to the green/magenta cases, the other cases are orange/cyan, yellowish‐green/purple, and yellow/violet. The success of the boundary color appearance model implies that bands are perceived as if the wavelength responses of the cones were essentially independent, which contradicts the actual behavior of cones. © 2014 Wiley Periodicals, Inc. Col Res Appl, 40, 135–146, 2015 相似文献
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Antonia Loibl Frank Marscheider-Weidemann Katrin Ostertag Sonja Rosenberg Luis Tercero Espinoza Matthias Pfaff Christian Sartorius 《化学,工程师,技术》2020,92(4):414-422
The socio-economic and ecological impacts of selected projects of the BMBF funding program “r4 – Innovative Technologies for Resource Efficiency – Research for the Provision of Raw Materials of Strategic Economic Importance” are presented. Many, but not all, research projects indicate a potential improvement of the supply situation in Germany. In some cases, the provision of secondary raw materials is unprofitable or ecologically detrimental. These cases require a balancing between security of supply and other economic and ecological objectives. 相似文献
9.
Current pot ventilation system is designed in a conservative manner to prevent hazardous gases from escaping aluminum smelting pots. Reduction of pot draft is an initiative of both efficiently using waste heat in the exhaust gas and significantly reducing fan power of the ventilation system. This work presents a systematic analysis on the reduction of pot draft and the consequent problem, ie, fugitive emissions from the smelting pot. Numerical models with different length scales are developed to simulate the fluid flow and heat transfer in pots and potroom. The superstructure of a typical aluminum smelting pot is successfully modified to maintain the pot tightness in the reducing pot draft. The results show that the current pot draft could be reduced by 50% at least using the developed technology. The techno-economic analysis of power generation from the waste heat in aluminum smelting pot is made based on organic Rankine cycle (ORC), and the potential benefits of using the pot exhaust gas of both normal and 50% reduced flow rates are estimated. It is found that the levelized energy cost of the optimized ORC system using 50% reduced exhaust gas is 0.048 $/kWh with a system's lifespan of 10 years and 0.038 $/kWh with a lifespan of 15 years while the payback time of investment is 5.2 years. 相似文献