SAR-943 (32-deoxo rapamycin) is a proliferation signal inhibitor via interaction with the mammalian target of rapamycin (mTOR). Most importantly, SAR-943 has improved chemical stability compared to rapamycin (sirolimus) and is currently under investigation as a drug coated on coronary stents. It was the goal of this study to identify the SAR-943 metabolites generated after incubation with human liver microsomes using high-resolution mass spectrometry (MS) and MS/iontrap (MS(n)) and comparison of fragmentation patterns of the metabolites with those of SAR-943 and other known rapamycin derivatives. Our study showed that SAR-943 is mainly hydroxylated and/or demethylated by human liver microsomes. The structures of the following metabolites were identified: O-demethylated metabolites: 39-O-desmethyl, 16-O-desmethyl and 27-O-desmethyl SAR-943; hydroxylated metabolites: hydroxy piperidine SAR-943, 11-hydroxy, 12-hydroxy, 14-hydroxy, 23-hydroxy, 24-hydroxy, 25-hydroxy, 46-hydroxy and 49-hydroxy SAR-943; didemethylated metabolites: 16,39-O-didesmethyl and 27,39-O-didesmethyl SAR-943; demethylated-hydroxylated metabolites: 39-O-desmethyl, 23- or 24-hydroxy and 39-O-desmethyl, hydroxy piperidine SAR-943 and dihydroxylated metabolites: 12-,23- or 24-dihydroxy SAR-943. In addition, several other demethylated-hydroxylated and dihydroxylated metabolites were detected. However, their exact structures could not be identified. 相似文献
A simultaneous visualization and measurement study on some specific points on demand curves, such as onset of nucleate boiling (ONB), onset of significant void (OSV), onset of flow instability (OFI), and two-phase flow patterns in a single-side heated narrow rectangular channel, having a width of 40 mm and a gap of 3 mm, was carried out. New experimental approaches were adopted to identify OSV and OFI in a narrow rectangular channel. Under experimental conditions, the ONB could be predicted well by the Sato and Matsumura model. The OSV model of Bowring can reasonably predict the OSV if the single-side heated condition is considered. The OFI was close to the saturated boiling point and could be described accurately by Kennedy’s correlation. The two-phase flow patterns observed in this experiment could be classified into bubbly, churn, and annular flow. Slug flow was never observed. The OFI always occurred when the bubbles at the channel exit began to coalesce, which corresponded to the beginning of the bubbly–churn transition in flow patterns. Finally, the evolution of specific points and flow pattern transitions were examined in a single-side heated narrow rectangular channel. 相似文献
In this paper, heavy crude oil–water flows are studied in a horizontal stainless steel test section with 25.4 mm ID and overall length of 50 m. Crude oil (viscosity = 628.1 mPa s, interfacial tension with water = 10.33 mN/m at 60 °C) and water, collected from an oilfield, were used as test fluids. Visual observations, local sampling and pressure drop measurements were used to identify the flow patterns and their transitions. It was found that in all conditions studied there was a water-in-oil emulsion present. At low mixture velocities and water fractions this occupied the whole pipe cross section. As the velocity or the volume fraction increased water appeared to segregate. At high water fractions and mixture velocities annular flow appeared with the water-in-oil emulsion in the core surrounded by a water layer. The results were compared with those from a model oil with the same viscosity. At low water fractions there was a similarity between the patterns observed with the two oil systems characterized by water segregation from an oil continuous dispersion with increasing water fraction or mixture velocity. However, at high water fractions an oil-in-water dispersion formed with the model oil that was not seen with the crude oil. Pressure drop was generally higher for the crude oil system compared to the model one, while in both cases it decreased when water started to segregate and form layers in contact with the pipe wall. The differences between the two oil systems are attributed to the natural surfactants present in the heavy crude oil (such as asphaltenes and resins), which tend to accumulate on the water/oil interface, retard film drainage and maintain the stability of water drops in oil. 相似文献
A reaction‐diffusion two‐predator‐one‐prey system with prey‐taxis describes the spatial interaction and random movement of predator and prey species, as well as the spatial movement of predators pursuing preys. The global existence and boundedness of solutions of the system in bounded domains of arbitrary spatial dimension and any small prey‐taxis sensitivity coefficient are investigated by the semigroup theory. The spatial pattern formation induced by the prey‐taxis is characterized by the Turing type linear instability of homogeneous state; it is shown that prey‐taxis can both compress and prompt the spatial patterns produced through diffusion‐induced instability in two‐predator‐one‐prey systems. 相似文献
In this paper, we concentrate on the spatiotemporal patterns of a delayed reaction‐diffusion Holling‐Tanner model with Neumann boundary conditions. In particular, the time delay that is incorporated in the negative feedback of the predator density is considered as one of the principal factors to affect the dynamic behavior. Firstly, a global Turing bifurcation theorem for τ = 0 and a local Turing bifurcation theorem for τ > 0 are given. Then, further considering the degenerated situation, we derive the existence of Bogdanov‐Takens bifurcation and Turing‐Hopf bifurcation. The normal form method is used to study the explicit dynamics near the Turing‐Hopf singularity. It is shown that a pair of stable nonconstant steady states (stripe patterns) and a pair of stable spatially inhomogeneous periodic solutions (spot patterns) could be bifurcated from a positive equilibrium. Moreover, the Turing‐Turing‐Hopf–type spatiotemporal patterns, that is, a subharmonic phenomenon with two spatial wave numbers and one temporal frequency, are also found and explained theoretically. Our results imply that the interaction of Turing and Hopf instabilities can be considered as the simplest mechanism for the appearance of complex spatiotemporal dynamics. 相似文献
This paper is primarily concern with the formulation and analysis of a reliable numerical method based on the novel alternating direction implicit finite difference scheme for the solution of the fractional reaction–diffusion system. In the work, the integer first‐order derivative in time is replaced with the Caputo fractional derivative operator. As a case study, the dynamics of predator–prey model is considered. In order to provide a good guidelines on the correct choice of parameters for the numerical simulation of full fractional reaction–diffusion system, its linear stability analysis is also examined. The resulting scheme is applied to solve both self‐diffusion and cross‐diffusion problems in two‐dimensions. We observed in the experimental results a range of spatiotemporal and chaotic structures that are related to Turing pattern. It was also discovered in the simulations that cross‐diffusive case gives rise to spatial patterns faster than the diffusive case. Apart from chaotic spiral‐like structures obtained in this work, it should also be mentioned that Turing patterns such as stationary spots and stripes are obtainable, depending on the initial and parameters choices. 相似文献
This paper proposes a new method for eliminating impulse noise. Based on the space characteristic of object and noise, three kinds of basic noise patterns are introduced to describe noise and detect noise candidates. Correspondingly, noise removal operators are presented to remove the impulse noise. Extensive experiment results have shown that the proposed method is better than some of the state-of-the-art methods. 相似文献
Currently surrogate data analysis can be used to determine if data is consistent with various linear systems, or something else (a nonlinear system). In this paper we propose an extension of these methods in an attempt to make more specific classifications within the class of nonlinear systems.
In the method of surrogate data one estimates the probability distribution of values of a test statistic for a set of experimental data under the assumption that the data is consistent with a given hypothesis. If the probability distribution of the test statistic is different for different dynamical systems consistent with the hypothesis, one must ensure that the surrogate generation technique generates surrogate data that are a good approximation to the data. This is often achieved with a careful choice of surrogate generation method and for noise driven linear surrogates such methods are commonly used.
This paper argues that, in many cases (particularly for nonlinear hypotheses), it is easier to select a test statistic for which the probability distribution of test statistic values is the same for all systems consistent with the hypothesis. For most linear hypotheses one can use a reliable estimator of a dynamic invariant of the underlying class of processes. For more complex, nonlinear hypothesis it requires suitable restatement (or cautious statement) of the hypothesis. Using such statistics one can build nonlinear models of the data and apply the methods of surrogate data to determine if the data is consistent with a simulation from a broad class of models. These ideas are illustrated with estimates of probability distribution functions for correlation dimension estimates of experimental and artificial data, and linear and nonlinear hypotheses. 相似文献
Because of the complicated geometry of the slotted structure, analytical theories of such structures are inevitably developed
on the basis of simplifying assumptions. On the other hand, the accuracy of the theory is of importance to the design of microwave
interaction structures. In this study, modes of the slotted waveguide are investigated analytically and simulated with the
HFSS code. It is shown that, in spite of the approximations made, the dispersion relation and field patterns of the standard
analytical theory are in excellent agreement with the HFSS simulations over the complete range of the slot depth. Modes not
built into the theory will also be noted. 相似文献