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1.
Henry Dring David Kreutzer Christoph Ritter Andreas Hilgeroth 《Molecules (Basel, Switzerland)》2021,26(1)
Despite the development of targeted therapies in cancer, the problem of multidrug resistance (MDR) is still unsolved. Most patients with metastatic cancer die from MDR. Transmembrane efflux pumps as the main cause of MDR have been addressed by developed inhibitors, but early inhibitors of the most prominent and longest known efflux pump P-glycoprotein (P-gp) were disappointing. Those inhibitors have been used without knowledge about the expression of P-gp by the treated tumor. Therefore the use of inhibitors of transmembrane efflux pumps in clinical settings is reconsidered as a promising strategy in the case of the respective efflux pump expression. We discovered novel symmetric inhibitors of the symmetric efflux pump MRP4 encoded by the ABCC4 gene. MRP4 is involved in many kinds of cancer with resistance to anticancer drugs. All compounds showed better activities than the best known MRP4 inhibitor MK571 in an MRP4-overexpressing cell line assay, and the activities could be related to the various substitution patterns of aromatic residues within the symmetric molecular framework. One of the best compounds was demonstrated to overcome the MRP4-mediated resistance in the cell line model to restore the anticancer drug sensitivity as a proof of concept. 相似文献
2.
3.
Marcel Oliver 《Theoretical and Computational Fluid Dynamics》1997,9(3-4):311-324
The so-called lake equations arise as the shallow-water limit of the rigid-lid equations—three-dimensional Euler equations
with a rigid-lid upper boundary condition—in a horizontally periodic basin with bottom topography. We prove an a priori estimate in the Sobolev space H
m
for m≥ 3 which shows that a solution to the rigid-lid equations can be approximated by a solution of the lake equations for an
interval of time which can be estimated in terms of the initial deviation from a columnar configuration and the magnitude
of the initial data in H
m
, the gradient of the bottom topography in H
m+1
, and the aspect ratio of the basin. In particular, any solution to the lake equations remains close to some solution of the
rigid-lid equations for an interval of time that can be made arbitrarily large by choosing the aspect ratio of the basin small.
Received 10 October 1996 and accepted 15 May 1997 相似文献
4.
von Eynatten G. Ritter T. Bömmel H. E. Dransfeld K. 《Zeitschrift für Physik B Condensed Matter》1987,65(3):341-345
A new model is presented which explains well the dramatic decrease of the Mössbauer line intensities with raising temperatures for freely dispersed iron microscrystals. In contrast to other theories which consider mainly vibration to be responsible we discuss here the decrease in terms of large amplitude diffusive rotational or translational jumps of the particles. Such diffusive jumps lead — in agreement with the observation — to a strong reduction of the Mössbauer-intensity without broadening the line width in a noticeable way. The typical potential well for a diffusing particle in an equilibrium position is derived quantitatively to be 13 meV. The model might be important also for a new understanding of the dynamics of catalytic clusters either in contact with each other or with larger solid surfaces.Part of this work was supported by the DFG Sonderforschungsbereich 306, Konstanz 相似文献
5.
Marcel Crabbé 《Comptes Rendus Mathematique》2004,338(6):433-436
We investigate the notion of substitution in an abstract way, without defining it explicitly. We single out the essential features of the operation of performing a substitution in order to define a concept of substitutive structure, called logos. We then prove a completeness theorem making precise and justifying the intuition that formulas true for the usual substitution can be proved from the logos axioms only. To cite this article: M. Crabbé, C. R. Acad. Sci. Paris, Ser. I 338 (2004). 相似文献
6.
Dedicated to the memory of John Oxtoby 相似文献
7.
Marcel Erné 《Order》1991,8(2):159-173
We introduce a special type of order-preserving maps between quasiordered sets, the so-called cut-stable maps. These form the largest morphism class such that the corresponding category of quasiordered sets contains the category of complete lattices and complete homomorphisms as a full reflective subcategory, the reflector being given by the Dedekind-MacNeille completion (alias normal completion or completion by cuts). Suitable restriction of the object class leads to the category of separated quasiordered sets and its full reflective subcategory of completely distributive lattices. Similar reflections are obtained for continuous lattices, algebraic lattices, etc. 相似文献
8.
M. Köhl A. Öttl S. Ritter T. Donner T. Bourdel T. Esslinger 《Applied physics. B, Lasers and optics》2007,86(3):391-393
We report an experimental investigation of two-particle correlations between neutral atoms in a Hanbury Brown and Twiss experiment.
Both an atom laser beam and a pseudo-thermal atomic beam are extracted from a Bose–Einstein condensate and the atom flux is
measured with a single atom counter. We determine the conditional and the unconditional detection probabilities for the atoms
in the beam and find good agreement with the theoretical predictions.
PACS 03.75.Pp; 05.30.Jp; 07.77.Gx; 42.50.Pq 相似文献
9.
We present a Bayesian theory of object identification. Here, identifying an object means selecting a particular observation from a group of observations (variants), this observation (the regular variant) being characterized by a distributional model. In this sense, object identification means assigning a given model to one of several observations. Often, it is the statistical model of the regular variant, only, that is known. We study an estimator which relies essentially on this model and not on the characteristics of the “irregular” variants. In particular, we investigate under what conditions this variant selector is optimal. It turns out that there is a close relationship with exchangeability and Markovian reversibility. We finally apply our theory to the case of irregular variants generated from the regular variant by a Gaussian linear model. 相似文献
10.
The syntheses of two rigid organic molecular rods bearing a nitronyl-nitroxide radical and a terminal nitrogen-based functionality like a pyridine or a cyano group are reported. Both new paramagnetic molecules are fully characterized, including crystal structure analysis. Furthermore their magnetic behaviours in the crystalline state are investigated and their spin concentration corroborate their excellent purity. While the pyridine functionalized rod is synthesized by converting the corresponding benzaldehyde to the phenyl-nitronyl-nitroxide radical, the synthesis of the cyano functionalized rod demonstrates the accessibility of highly sophisticated spin-labelled molecules via cross-coupling reaction with a meta-iodo-phenyl-nitronyl-nitroxide moiety. 相似文献