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991.
Simultaneous Multiple MS Binding Assays for the Dopamine,Norepinephrine, and Serotonin Transporters
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Patrick Neiens Dr. Angela De Simone Dr. Georg Höfner Prof. Dr. Klaus T. Wanner 《ChemMedChem》2018,13(5):453-463
In this work, we present label‐free, mass‐spectrometry‐based binding assays (MS Binding Assays), targeting the human dopamine, norepinephrine, and serotonin transporters (hDAT, hNET, and hSERT) in simultaneous binding experiments. Using a validated LC–ESI‐MS/MS method for quantification of the selective dopamine transporter inhibitor (R,R)‐4‐(2‐benzhydryloxyethyl)‐1‐(4‐fluorobenzyl)piperidin‐3‐ol ((R,R)‐D‐84), the selective norepinephrine transporter inhibitor (S,S)‐reboxetine, and the selective serotonin reuptake inhibitor (S)‐citalopram, binding affinities at the three monoamine transporters could be characterized simultaneously in a single binding experiment. The performed simultaneous saturation and competition experiments yielded results that are in good accordance with those determined in MS Binding Assays addressing the monoamine transporters individually. The results obtained from this study underscore the potential of MS Binding Assays for simultaneous affinity determination at different targets, which is difficult to accomplish with conventional radioligand binding assays. 相似文献
992.
Synthesis of a Series of Structurally Diverse MB327 Derivatives and Their Affinity Characterization at the Nicotinic Acetylcholine Receptor
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Sebastian Rappenglück Sonja Sichler Dr. Georg Höfner Dr. Thomas Wein Karin V. Niessen Dr. Thomas Seeger Prof. Dr. Franz F. Paintner Prof. Dr. Franz Worek Prof. Dr. Horst Thiermann Prof. Dr. Klaus T. Wanner 《ChemMedChem》2018,13(17):1806-1816
A novel series of 30 symmetric bispyridinium and related N‐heteroaromatic bisquaternary salts with a propane‐1,3‐diyl linker was synthesized and characterized for their binding affinity at the MB327 binding site of nicotinic acetylcholine receptor (nAChR) from Torpedo californica. Compounds targeting this binding site are of particular interest for research into new antidotes against organophosphate poisoning, as therapeutically active 4‐tert‐butyl‐substituted bispyridinium salt MB327 was previously identified as a nAChR re‐sensitizer. Efficient access to the target compounds was provided by newly developed methods enabling N‐alkylation of sterically hindered or electronically deactivated heterocycles exhibiting a wide variety of functional groups. Determination of binding affinities toward the MB327 binding site at the nAChR, using a recently developed mass spectrometry (MS)‐based Binding Assay, revealed that several compounds reached affinities similar to that of MB327 (pKi=4.73±0.03). Notably, the newly prepared lipophilic 4‐tert‐butyl‐3‐phenyl‐substituted bispyridinium salt PTM0022 ( 3 h ) was found to have significantly higher binding affinity, with a pKi value of 5.16±0.07, thus representing considerable progress toward the development of more potent nAChR re‐sensitizers. 相似文献
993.
Klaus M. Zwilsky Nicholas J. Grant 《JOM Journal of the Minerals, Metals and Materials Society》1957,9(10):1197-1201
Utilizing relatively coarse copper powders and several sizes of silica and alumina powders, alloys containing up to 10 volume pct of oxide were made. The alloys were prepared by mechanical mixing of powders, followed by cold hydrostatic pressing, sintering, and hot extrusion. Measurements were made of room temperature tensile properties, recrystallization temperature, creep rupture properties from 250° to 450°C, and resistivity. In addition, metallographic studies were made of the resultant structures. Of particular interest was the stability of the structure with respect to temperature, time, and stress. 相似文献
994.
Archimedes’ principle was applied to strand lengths of up to 14 m of round 177 mm diameter billets to determine cavity volume V (in cm3/m) for a series of tubemaking steels. Under steady state casting conditions, V depends primarily on the chemical composition and solidification behaviour of the steels. Averages ranged up to in an extreme case (bearing steel; vC = 2.0 m/min). Stopping the strand and abrupt lowering of withdrawal speed made it possible to artificially induce individual shrinkage cavities with peak values of V = 45 cm3/m. In the round mould, subsequent necking of the liquid crater is initiated in this process. Whisker-like and icicle-like dendrites can be observed in horizontally formed macroscopic shrinkage cavities. The liquid crater is broken off by periodic bridging (the mini-lingot model). As permeability decreases, the bridges deflect downward in a U-shape under the ferrostatic load. The residual inter-dendritic melt is squeezed out in this plastic deformation process. Some bridges ultimately break. This interpretation is based on comprehensive CMA studies and concentration maps. Cores taken from the centre of a strand of bearing steel were submitted to various heat treatments between 1100 and 1350°C. Homogenization occurs below solidus (T < 1225°C). Carbides dissolve and sulfides become globular. Spatial segregation, on the other hand, increases, above solidus. In the extreme case at 1350°C/30 h, the residual melt at the grain boundaries migrates practically completely from the surface zone to the centre of the cylindrical sample (40 mm diameter). The propellent forces for this macro-heterogenization are provided by the activity gradient from the cylindrical surface to the centre and minimization of interface energy γ/I. 相似文献
995.
Electrochemically Active Polymers for Rechargeable Batteries 总被引:3,自引:0,他引:3
996.
Oxygen activities in Fe-O-Cr melts, equilibrated with chromium oxide, were determined as a function of chromium content by EMF measurements using ZrO2(CaO) plug-type sensors with a Cr-Cr2O3 reference. Plug-type sensors with or without Cr2O3 saturator were used in the experiments. From the experimental results values for the activity coefficient fO and the interaction parameters and were evaluated. Raoultian chromium activity features a slight positive deviation from ideal solution behaviour in the temperature range from 1550 to 1650°C. Taking into account the calculated interaction parameters, the equilibrium constant KCr-O was redetermined at 1550 to 1650°C. In comparison with previous studies a better agreement was obtained with existing thermochemical data. 相似文献
997.
Foued Ameur Paul Fischer Klaus -U. Höffgen Friedhelm Meyer auf der Heide 《Acta Informatica》1996,33(5):621-630
A pac-learning algorithm isd-space bounded, if it stores at mostd examples from the sample at any time. We characterize thed-space learnable concept classes. For this purpose we introduce the compression parameter of a concept classb and design our Trial and Error Learning Algorithm. We show: b isd-space learnable if and only if the compression parameter ofb is at mostd. This learning algorithm does not produce a hypothesis consistent with the whole sample as previous approaches e.g. by Floyd, who presents consistent space bounded learning algorithms, but has to restrict herself to very special concept classes. On the other hand our algorithm needs large samples; the compression parameter appears as exponent in the sample size. We present several examples of polynomial time space bounded learnable concept classes: - all intersection closed concept classes with finite VC-dimension. - convexn-gons in ?2. - halfspaces in ?n. - unions of triangles in ?2. We further relate the compression parameter to the VC-dimension, and discuss variants of this parameter. 相似文献
998.
We provide a view of the literature aging features in the sciences and social sciences, at different aggregation levels, of major fields, subfields, journals and individual papers and from different perspectives. Against to the wide belief that scientific literature may become more rapidly obsolete, we found that, in general, the share of more recent references were distinctly lower in 2014 than that in 1992, which holds for all aggregation levels. As exceptions, the subfields related to Chemistry and the subfield energy and fuels, have shown a clear trend to cite more recent literature than older articles. Particle and nuclear physics and astronomy and astrophysics, the two subfields which strongly rely on e-print archives, have shown a ‘polarization’ tendency of reference distribution. Furthermore, we stress that it is very important to measure the Price Index at the paper level to account for differences between the documents published in the same journals and (sub-)fields. 相似文献
999.
Irina Akhmetova Konstantin Schutjajew Manuel Wilke Ana Buzanich Klaus Rademann Christina Roth Franziska Emmerling 《Journal of Materials Science》2018,53(19):13390-13399
Two divalent manganese aminophosphonates, manganese mono(nitrilotrimethylphosphonate) (MnNP3) and manganese bis(N-(carboxymethyl)iminodi(methylphosphonate)) (Mn(NP2AH)2), have been prepared by mechanochemical synthesis and characterized by powder X-ray diffraction (PXRD). The structure of the novel compound Mn(NP2AH)2 was determined from PXRD data. MnNP3 as well as Mn(NP2AH)2 exhibits a chain-like structure. In both cases, the manganese atom is coordinated by six oxygen atoms in a distorted octahedron. The local coordination around Mn was further characterized by extended X-ray absorption fine structure. The synthesis process was followed in situ by synchrotron X-ray diffraction revealing a three-step reaction mechanism. The as-prepared manganese(II) phosphonates were calcined on air. All samples were successfully tested for their suitability as catalyst material in the oxygen evolution reaction. 相似文献
1000.