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31.
Annabelle Ballesta Jean Clairambault Sandrine Dulong Francis Levi 《Applied Mathematics Letters》2011,24(7):1251-1256
The anticancer drug Irinotecan (CPT11) is known to trigger the induction of ATP-Binding Cassette (ABC) transporters, responsible for the efflux of the drug and its metabolites outside of the cells. The drug-modulated overexpression of those transporters prevents its accumulation in the intracellular medium, therefore decreasing its efficacy. A critical clinical concern lies in the design of CPT11-based therapeutic strategies which eradicate a maximum number of cancer cells despite their ability to become resistant. In order to address this issue, we supplemented an existing mathematical model of CPT11 molecular pharmacokinetics–pharmacodynamics (PK–PD) with a new model of CPT11-induced overexpression of ABC transporters. We then theoretically optimized exposure to CPT11 given as a single agent or combined either with ABC transporter inhibitors, or with inhibitors of nuclear factors whose activation is responsible for transporter overexpression. We firstly considered a cancer cell population endowed with the ability of inducing their transporters. For any drug combination, we concluded that the highest concentration of CPT11 should be administered in order to kill a maximum number of cancer cells, despite the triggering of resistance. We then considered a population of healthy cells which were assumed to be identical to cancer cells except that they were not able to become resistant. Optimal schemes were defined as the ones which maximized DNA damage in cancer cells under the constraint of DNA damage in healthy cells not exceeding a tolerability threshold. The optimal therapeutic strategy consisted in combining CPT11 with ABC transporter inhibitors as it achieved a complete reversal of resistance by means of the lowest concentrations of CPT11. 相似文献
32.
An expeditious synthesis of 1-epitrehazolamine is presented from readily available 2,3,4,6-tetra-O-benzyl-D-glucose. The key step involves a samarium diiodide-promoted reductive cyclization of a masked keto-nitrone to form a five-membered ring aminocyclitol. The excellent cis selectivity observed in this nitrone-ketone reductive coupling contrasts surprisingly with the trans selectivity of ketone-oxime reductive couplings. 相似文献
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A new three-component domino reaction catalyzed by palladium was devised, producing polysubstituted bicyclic molecules in good yields from readily available substrates. The reaction conditions and the scope of the process were examined, and a possible mechanism is proposed. [reaction: see text] 相似文献
35.
László Erdős Sandrine Péché José A. Ramírez Benjamin Schlein Horng‐Tzer Yau 《纯数学与应用数学通讯》2010,63(7):895-925
We consider N × N Hermitian Wigner random matrices H where the probability density for each matrix element is given by the density ν(x) = e?U(x). We prove that the eigenvalue statistics in the bulk are given by the Dyson sine kernel provided that U ∈ C6( \input amssym $\Bbb R$ ) with at most polynomially growing derivatives and ν(x) ≥ Ce?C|x| for x large. The proof is based upon an approximate time reversal of the Dyson Brownian motion combined with the convergence of the eigenvalue density to the Wigner semicircle law on short scales. © 2010 Wiley Periodicals, Inc. 相似文献
36.
An efficient route to a 5,6-dihydropyrano[3,4-b]pyridin-8-one core in two steps from enaminolactones
Cheikh Sall Sandrine Paquelet Jean Michel Chezal Yves Blache 《Tetrahedron letters》2008,49(8):1301-1304
A convenient two step conversion of heterocyclic enaminolactones to heterocyclic fused 2-pyran-1-ones is reported. The use of this method can be applied to a wide variety of aromatic and heteroaromatic amines to give potentially biologically active compounds in good yields. 相似文献
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Efficient reaction conditions have been developed to prepare highly functionalized chiral pyranosido-pyrimidine by regioselective alkylation of the pyranoside ring and palladium-catalyzed cross-coupling reaction on the pyrimidine ring under microwave activation. Such scaffold contains three different functions suitable for selective derivatization and could find applications in the design of peptidomimetics. 相似文献
39.
Aline Bonami Sandrine Grellier Mohammad Kacim 《Transactions of the American Mathematical Society》2008,360(3):1377-1390
We extend to multilinear Hankel operators the fact that some truncations of bounded Hankel operators are still bounded. We prove and use a continuity property of bilinear Hilbert transforms on products of Lipschitz spaces and Hardy spaces.
40.
Hannah DC Dunn NJ Ithurria S Talapin DV Chen LX Pelton M Schatz GC Schaller RD 《Physical review letters》2011,107(17):177403
We report heat dissipation times in semiconductor nanocrystals of CdSe. Specifically, a previously unresolved, subnanosecond decay component in the low-temperature photoluminescence decay dynamics exhibits longer decay lifetimes (tens to hundreds of picoseconds) for larger nanocrystals as well as a size-independent, ~25-meV spectral shift. We attribute the fast relaxation to transient phonon-mediated relaxation arising from nonequilibrium acoustic phonons. Following acoustic phonon dissipation, the dark exciton state recombines more slowly via LO-phonon assistance resulting in the observed spectral shift. The measured relaxation time scales agree with classical calculations of thermal diffusion, indicating that interfacial thermal conductivity does not limit thermal transport in these semiconductor nanocrystal dispersions. 相似文献