A novel HIF (hypoxia-inducible factor)-1α inhibitor, the (aryloxyacetylamino)benzoic acid derivative LW6, is an anticancer agent that inhibits the accumulation of HIF-1α. The aim of this study was to characterize and determine the structures of the metabolites of LW6 in ICR mice. Metabolite identification was performed using a predictive multiple reaction monitoring-information dependent acquisition-enhanced product ion (pMRM-IDA-EPI) method in negative ion mode on a hybrid triple quadrupole-linear ion trap mass spectrometer (QTRAP). A total of 12 metabolites were characterized based on their MS/MS spectra, and the retention times were compared with those of the parent compound. The metabolites were divided into five structural classes based on biotransformation reactions: amide hydrolysis, ester hydrolysis, mono-oxidation, glucuronidation, and a combination of these reactions. From this study, 2-(4-((3r,5r,7r)-adamantan-1-yl)phenoxy)acetic acid (APA, M7), the metabolite produced via amide hydrolysis, was found to be a major circulating metabolite of LW6 in mice. The results of this study can be used to improve the pharmacokinetic profile by lowering the clearance and increasing the exposure relative to LW6. 相似文献
Hot-wire measurement and multi-smoke wire flow visualization method are employed to study vortex pairing in the jet column
mode under two-frequency forcing with controlled initial phase differences. For the range of 0.3<StD<0.6, vortex pairing can be easily controlled by means of the fundamental and its subharmonic forcing with varying initial
phase differences. As stable vortex pairing dominates, the variation of the subharmonic component with the initial phase difference
changes from a sine shape to a cusp-like shape. The harmonics of the subharmonic also show similar trends. The detuning induces
the amplitude and phase modulations of the u-signal in the time trace and the sideband growth in the spectra. The u-signal reflects the subharmonic variation with the initial phase difference in its envelope. For 0.6<StD<0.9, non-pairing advection of vortices due to improper phase difference is sometimes observed under single-frequency forcing.
In this case, vortex pairing can be made to occur by the addition of a subharmonic with very small amplitude. As the initial
level of this subharmonic is increased, the onset position of vortex pairing moves upstream. In this range, the initial phase
difference is not an effective parameter in controlling vortex pairing.
Received: 22 May 1997 / Accepted: 16 October 1997 相似文献
Analytical solutions for the plane Couette flow and the plane Poiseuille flow of the one-mode Giesekus fluid without any retardation time have been obtained by considering the domain of definition for each of the two branch solutions which arise due to the presence of the quadratic stress terms in the constitutive equations. For each fixed value of the mobility parametera, the limiting value of the Weissenberg number for the upper branch solution, i.e., the physically realistic solution is determined in terms of the corresponding dimensionless shear stress for the plane Couette flow and in terms of the corresponding dimensionless pressure gradient for the plane Poiseuille flow. In the case of the plane Couette flow, it is shown that fora falling in the range 0a1/2 only the physically realistic solution exists while for 1/2<a 1 a nonphysical solution coexists with the realistic one. In the case of the plane Poiseuille flow, it is shown that the non-physical solution cannot even exist around the center plane of the channel, and the effects of the mobility parameter and the dimensionless pressure gradient on the flow variables are investigated. Possible extensions of the present approach to other steady simple shear flows with and without the introduction of the retardation time are also discussed. 相似文献
Three‐dimensional (3D) carbon nitride (C3N4)‐based materials show excellent performance in a wide range of applications because of their suitable band structures. To realize the great promise of two‐dimensional (2D) allotropes of various 3D materials, it is highly important to develop routes for the production of 2D C3N4 materials, which are one‐atom thick, in order to understand their intrinsic properties and identify their possible applications. In this work, water‐dispersible, atomically thin, and small carbon nitride nanodots were produced using the chemical oxidation of graphitic C3N4. Various analyses, including X‐ray diffraction, X‐ray photoelectron, Fourier‐transform infrared spectroscopy, and combustion‐based elemental analysis, and thermogravimetric analysis, confirmed the production of 3D oxidized C3N4 materials. The 2D C3N4 nanodots were successfully exfoliated as individual single layers; their lateral dimension was several tens of nanometers. They showed strong photoluminescence in the visible region as well as excellent performances as cell‐imaging probes in an in vitro study using confocal fluorescence microscopy. 相似文献
A single function approximation (SFA) approach for event-triggered output-feedback tracker design is presented for uncertain nonlinear time-delay systems in lower-triangular form. Contrary to the existing event-triggered output-feedback control methods dependent on multiple function approximators in the presence of lower-triangular nonlinearities, the proposed SFA approach provides the following advantages: (i) the simple observer structure independent of function approximators; (ii) one event-triggering condition based on only a tracking error; and (iii) the simple control scheme using one function approximator. Thus, the structural simplicity is allowed for implementing the observer and the event-triggering law in the sensor part and the adaptive tracker in the control part. Under the proposed SFA-based event-triggered control scheme, it is shown that the boundedness of closed-loop signals and the existence of a minimum inter-event time are guaranteed regardless of unknown time-delay nonlinearities and unmeasurable state variables.
Mathematische Zeitschrift - Mazur’s fundamental work on the Eisenstein ideal of prime level has a variety of arithmetic applications. In this article, we generalize some of his work to... 相似文献