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1.
Mycophenolic acid (MPA), a frequently used immunosuppressant, exhibits large inter‐patient pharmacokinetic variability. This study (a) developed and validated a sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) assay for MPA and metabolites [MPA glucuronide (MPAG) and acyl‐glucuronide (AcMPAG)] in the culture medium of HepaRG cells; and (b) characterized the metabolism interaction between MPA and p‐cresol (a common uremic toxin) in this in vitro model as a potential mechanism of pharmacokinetic variability. Chromatographic separation was achieved with a C18 column (4.6 × 250 mm,5 μm) using a gradient elution with water and methanol (with 0.1% formic acid and 2 mm ammonium acetate). A dual ion source ionization mode with positive multiple reaction monitoring was utilized. Multiple reaction monitoring mass transitions (m/z) were: MPA (320.95 → 207.05), MPAG (514.10 → 303.20) and AcMPAG (514.10 → 207.05). MPA‐d3 (323.95 → 210.15) and MPAG‐d3 (517.00 → 306.10) were utilized as internal standards. The calibration curves were linear from 0.00467 to 3.2 μg/mL for MPA/MPAG and from 0.00467 to 0.1 μg/mL for AcMPAG. The assay was validated based on industry standards. p‐Cresol inhibited MPA glucuronidation (IC50 ≈ 55 μm ) and increased MPA concentration (up to >2‐fold) at physiologically relevant substrate‐inhibitor concentrations (n = 3). Our findings suggested that fluctuations in p‐cresol concentrations might be in part responsible for the large pharmacokinetic variability observed for MPA in the clinic. 相似文献
2.
Motivated by the quasi-local mass problem in general relativity, we study the rigidity of isometric immersions with the same mean curvature into a warped product space. As a corollary of our main result, two star-shaped hypersurfaces in a spatial Schwarzschild or AdS-Schwarzschild manifold with nonzero mass differ only by a rotation if they are isometric and have the same mean curvature. We also prove similar results if the mean curvature condition is replaced by an -curvature condition. 相似文献
3.
Antonio Kumpera 《Journal of Differential Equations》2019,266(2-3):911-935
We first discuss the problems in the theory of ordinary differential equations that gave rise to the concept of a flag system and illustrate these with the Cartan criterion for Monge equations (1st order) as well as the Cartan statement concerning the local equivalence of Monge–Ampère type equations (2nd order). Next, we describe a prolongation functor operating on the infinitesimal symmetries (automorphisms) of the Darboux flag and extending these, isomorphically, to all the symmetries of any other flag. Hence, flag systems cannot be distinguished by their symmetry algebras and the local classification of these objects is approached by considering higher order isotropies of these algebras as well as the groupoids of k-th order formal equivalences since the differential equations defining the latter provide precious information for the application of flag systems to differential equations (e.g., Cartan's criterion for non-linear Monge equations). In examining the behavior of the isotropy algebras, that can either diminish or remain the same, when passing from a derived system to the consecutive system , we obtain a full set of numerical invariants for the elementary flag systems that moreover specifies the local models. 相似文献
4.
The radius of spatial analyticity for solutions of the KdV equation is studied. It is shown that the analyticity radius does not decay faster than as time t goes to infinity. This improves the works of Selberg and da Silva (2017) [30] and Tesfahun (2017) [34]. Our strategy mainly relies on a higher order almost conservation law in Gevrey spaces, which is inspired by the I-method. 相似文献
5.
Charles Almeida Aline V. Andrade Rosa M. Miró-Roig 《Journal of Pure and Applied Algebra》2019,223(4):1817-1831
Let be a minimal monomial Togliatti system of forms of degree d. In [4], Mezzetti and Miró-Roig proved that the minimal number of generators of lies in the interval . In this paper, we prove that for and , the integer values in cannot be realized as the number of minimal generators of a minimal monomial Togliatti system. We classify minimal monomial Togliatti systems of forms of degree d with or 3n (i.e. with the minimal number of generators reaching the border of the non-existence interval). Finally, we prove that for , and there exists a minimal monomial Togliatti system of forms of degree d with . 相似文献
6.
This paper will deal with an anisotropic area-preserving flow which keeps the convexity of the evolving curve and the limiting curve converges to a homothety of a symmetric smooth strictly convex plane curve. 相似文献
7.
Timothy Buttsworth 《Mathematische Nachrichten》2019,292(4):747-759
Let G be a three‐dimensional unimodular Lie group, and let T be a left‐invariant symmetric (0,2)‐tensor field on G. We provide the necessary and sufficient conditions on T for the existence of a pair consisting of a left‐invariant Riemannian metric g and a positive constant c such that , where is the Ricci curvature of g. We also discuss the uniqueness of such pairs and show that, in most cases, there exists at most one positive constant c such that is solvable for some left‐invariant Riemannian metric g. 相似文献
8.
George Victor McIlvaine 《Expositiones Mathematicae》2019,37(3):333-346
This paper reports on findings relating to catenaries since the publication in Expositiones Mathematicae of Denzler and Hinz’s pioneering 1999 paper, Catenaria Vera – the True Catenary. New governing differential equations and explicit solutions are derived for the catenary in positive and negative radial potentials with physical constants incorporated in the derivations. In keeping with precedent by Denzler and Hinz, a measure of historical perspective is offered as homage to Gottfried Wilhelm Leibniz, Christiaan Huygens and Johann Bernoulli, the original first-solvers of the catenary. 相似文献
9.
Johannes Wittmann 《Mathematische Nachrichten》2019,292(7):1627-1635
Let M be a closed spin manifold and let N be a closed manifold. For maps and Riemannian metrics g on M and h on N, we consider the Dirac operator of the twisted Dirac bundle . To this Dirac operator one can associate an index in . If M is 2‐dimensional, one gets a lower bound for the dimension of the kernel of out of this index. We investigate the question whether this lower bound is obtained for generic tupels . 相似文献
10.