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1.
Tumor and inflammation have many common features. One hallmark of both is enhanced vascular permeability, which is mediated by various factors including bradykinin, nitric oxide (NO), peroxynitrite, prostaglandins etc. A unique characteristic of tumors, however, is defective vascular anatomy. The enhanced vascular permeability in tumors is also distinctive in that extravasated macromolecules are not readily cleared. We utilized the enhanced permeability and retention (EPR) effect of tumors for tumor selective delivery of macromolecular drugs. Consequently, such drugs, nanoparticles or lipid particles, when injected intravenously, selectively accumulate in tumor tissues and remain there for long periods. The EPR effect of tumor tissue is frequently inhomogeneous and the heterogeneity of the EPR effect may reduce the tumor delivery of macromolecular drugs. Therefore, we developed methods to augment the EPR effect without inducing adverse effects for instance raising the systemic blood pressure by infusing angiotensin II during arterial injection of SMANCS/Lipiodol. This method was validated in clinical setting. Further, benefits of utilization of NO-releasing agent such as nitroglycerin or angiotensin-converting enzyme (ACE) inhibitors were demonstrated. The EPR effect is thus now widely accepted as the most basic mechanism for tumor-selective targeting of macromolecular drugs, or so-called nanomedicine.  相似文献   

2.
We present two types of Molecular Dynamics (MD) simulation for calculating the desorption rate of molecules from a surface. In the first, the molecules move freely between two surfaces, and the desorption rate is obtained either by counting the number of desorption events in a given time, or by looking at the average density of the molecules as a function of distance from the surface and then applying transition state theory (TST). In the second, the potential of mean force (PMF) for a molecule is determined as a function of distance from the surface and the desorption rate is obtained by means of TST. The methods are applied to water on the MgO(0 0 1) surface at low coverage. Classical potentials are used so that long simulations can be performed, to minimise statistical errors. The two sets of MD simulations agree well at high temperatures. The PMF method reproduces the 0 K adsorption energy of the molecule to within 5 meV, and finds that the well depth of the PMF is not linear with temperature. This implies the prefactor frequency f in the Polanyi-Wigner equation is a function of temperature, increasing at lower temperatures due to the reduction of the available configuration space associated with an adsorbed molecule compared with a free molecule.  相似文献   

3.
The effect of an external magnetic field on the L3 subshell fluorescence yields (ω3 ) and level widths ($\Gamma_{L_3}$) for paramagnetic Ta, W, Tl, Th and U have been investigated using the 59.54 keV incident photon energy in the external magnetic field of intensities ±0.60 T. L3 X-ray fluorescence cross sections ($\sigma_{L_3}^{X}$) have been measured for the same elements. The measured ω 3, $\Gamma_{L_3} $ and $ \sigma_{L_3}^X$ values for B = 0 are in good agreement with the theoretical values. It was observed that the values of $\sigma_{L_3}^X$ and ω3 with the applied magnitude of the magnetic field in both directions show a decreasing trend for paramagnetic Ta, W, Tl, Th and U. Furthermore, in the presence of an external magnetic field, the values of $\Gamma_{L_3}$ show an increasing trend for the same elements. The results show that the atomic parameters such as spectral linewidth, radiation rates, photoionization cross section and fluorescence yield can change when the irradiation is conducted in a magnetic field.  相似文献   

4.
I.A. Shalimova 《Physica A》2010,389(21):4436-4449
The response of an elastic half-space to random excitations of displacements on the boundary under the condition of no shearing forces is studied. We analyze the white noise excitations and general random fluctuations of displacements prescribed on the boundary. We consider the case of partially ordered defects on the boundary whose positions are governed by an exponential-cosine-type correlation function. The analysis is based on a Poisson-type integral formula which we derive here for the case of zero shearing forces on the boundary. We obtain exact representations for the displacement correlation tensor and the Karhunen-Loève expansion for the solution of the Lamé equation itself, and analyze some features of the correlation structure of the displacements. The Monte Carlo technique developed can be applied to a wide class of differential equations with random boundary conditions.  相似文献   

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