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排序方式: 共有271条查询结果,搜索用时 15 毫秒
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Diane S. Abou Nikki A. Thiele Nicholas T. Gutsche Alexandria Villmer Hanwen Zhang Joshua J. Woods Kwamena E. Baidoo Freddy E. Escorcia Justin J. Wilson Daniel L. J. Thorek 《Chemical science》2021,12(10):3733
Targeted alpha therapy is an emerging strategy for the treatment of disseminated cancer. [223Ra]RaCl2 is the only clinically approved alpha particle-emitting drug, and it is used to treat castrate-resistant prostate cancer bone metastases, to which [223Ra]Ra2+ localizes. To specifically direct [223Ra]Ra2+ to non-osseous disease sites, chelation and conjugation to a cancer-targeting moiety is necessary. Although previous efforts to stably chelate [223Ra]Ra2+ for this purpose have had limited success, here we report a biologically stable radiocomplex with the 18-membered macrocyclic chelator macropa. Quantitative labeling of macropa with [223Ra]Ra2+ was accomplished within 5 min at room temperature with a radiolabeling efficiency of >95%, representing a significant advancement over conventional chelators such as DOTA and EDTA, which were unable to completely complex [223Ra]Ra2+ under these conditions. [223Ra][Ra(macropa)] was highly stable in human serum and exhibited dramatically reduced bone and spleen uptake in mice in comparison to bone-targeted [223Ra]RaCl2, signifying that [223Ra][Ra(macropa)] remains intact in vivo. Upon conjugation of macropa to a single amino acid β-alanine as well as to the prostate-specific membrane antigen-targeting peptide DUPA, both constructs retained high affinity for 223Ra, complexing >95% of Ra2+ in solution. Furthermore, [223Ra][Ra(macropa-β-alanine)] was rapidly cleared from mice and showed low 223Ra bone absorption, indicating that this conjugate is stable under biological conditions. Unexpectedly, this stability was lost upon conjugation of macropa to DUPA, which suggests a role of targeting vectors in complex stability in vivo for this system. Nonetheless, our successful demonstration of efficient radiolabeling of the β-alanine conjugate with 223Ra and its subsequent stability in vivo establishes for the first time the possibility of delivering [223Ra]Ra2+ to metastases outside of the bone using functionalized chelators, marking a significant expansion of the therapeutic utility of this radiometal in the clinic.The therapeutic alpha-emitter 223Ra can be stably complexed in vivo, creating opportunities for the development of targeted radiopharmaceutical agents with this radionuclide. 相似文献
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The paper deals with two-dimensional slow-fast systems and more specifically with multi-layer canard cycles. These are canard cycles passing through n layers of fast orbits, with n?2. The canard cycles are subject to n generic breaking mechanisms and we study the limit cycles that can be perturbed from the generic canard cycles of codimension n. We prove that this study can be reduced to the investigation of the fixed points of iterated translated power functions. 相似文献
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Julien Barré Freddy Bouchet Thierry Dauxois Stefano Ruffo 《Journal of statistical physics》2005,119(3-4):677-713
We discuss a method to solve models with long-range interactions in the microcanonical and canonical ensemble. The method closely follows the one introduced by R.S. Ellis, Physica D 133:106 (1999), which uses large deviation techniques. We show how it can be adapted to obtain the solution of a large class of simple models, which can show ensemble inequivalence. The model Hamiltonian can have both discrete (Ising, Potts) and continuous (HMF, Free Electron Laser) state variables. This latter extension gives access to the comparison with dynamics and to the study of non-equilibrium effects. We treat both infinite range and slowly decreasing interactions and, in particular, we present the solution of the α-Ising model in one-dimension with 0
⩽ α < 1. 相似文献
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Dr. Rubén Orihuela Freddy Monteiro Dr. Ayelén Pagani Prof. Mercè Capdevila Prof. Sílvia Atrian 《Chemistry (Weinheim an der Bergstrasse, Germany)》2010,16(41):12363-12372
It has previously been shown that recombinant synthesis, under metal‐supplemented conditions, of diverse metallothioneins (MTs) results in the recovery of a subpopulation of S2?‐containing complexes in addition to the S2?‐devoid canonical metal–MT species. Further significance of this finding has remained veiled by the possibility of it being a mere consequence of synthesis in a heterologous bacterial system. Herein, we present definitive evidence that S2? ligands are also constituents of native metal–MT complexes. Because, although practically universal, the highest S2? content is incorporated by copper‐thioneins when coordinating divalent metal ions, we adapted the Saccharomyces cerevisiae Cup1 protein, which is the most paradigmatic copper‐thionein, as an experimental model. Most significantly, native Cd–Cup1 complexes were purified and fully spectroscopically and spectrometrically characterized from the 301N mutant yeast strain, which allows Cup1 synthesis even in the absence of copper. These results undoubtedly revealed the presence of a Cd–S2?–Cup1 species in native preparations, which were only recovered when carefully avoiding the use of ion‐exchange chromatography in the purification protocol. Furthermore, complete analysis of recombinant (Escherichia coli) Zn–Cup1, Cd–Cup1, and Cu–Cup1 and those complexes that result from Zn/Cd and Zn/Cu replacements in vitro and acidification/renaturalization processes yielded a comprehensive and comparative overview of the metal‐binding abilities of Cup1. Overall, we consider the main conclusions of this study to go beyond the mere study of the particular Cup1 MT, so that they should be considered to delineate a new point of view on the interaction between copper‐thioneins and divalent metal ions, still an unexplored aspect in MT research. 相似文献
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In this paper we introduce a kind of “noncommutative neighbourhood” of a semiclassical parameter corresponding to the Planck
constant. This construction is defined as a certain filtered and graded algebra with an infinite number of generators indexed
by planar binary leaf-labelled trees. The associated graded algebra (the classical shadow) is interpreted as a “distortion”
of the algebra of classical observables of a physical system. It is proven that there exists a q-analogue of the Weyl quantization, where q is a matrix of formal variables, which induces a nontrivial noncommutative analogue of a Poisson bracket on the classical
shadow. 相似文献
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Peter De Maesschalck Freddy Dumortier Robert Roussarie 《Comptes Rendus Mathematique》2014,352(4):317-320
We introduce transitory canard cycles for slow–fast vector fields in the plane. Such cycles separate “canards without head” and “canards with head”, like for example in the Van der Pol equation. We obtain optimal upper bounds on the number of periodic orbits that can appear near the cycle under whatever condition on the related slow divergence integral I , including the challenging case I=0. 相似文献