Development,In-Vitro Characterization and Preclinical Evaluation of Esomeprazole-Encapsulated Proniosomal Formulation for the Enhancement of Anti-Ulcer Activity

Objective: The present study aimed to develop and optimize esomeprazole loaded proniosomes (EZL-PNs) to improve bioavailability and therapeutic efficacy. Method: EZL-PNs formulation was developed by slurry method and optimized by 33 box-Bhekhen statistical design software. Span 60 (surfactant), cholesterol, EZL concentration were taken as independent variables and their effects were evaluated on vesicle size (nm), entrapment efficiency (%, EE) and drug release (%, DR). Furthermore, optimized EZL-PNs (EZL-PNs-opt) formulation was evaluated for ex vivo permeation, pharmacokinetic and ulcer protection activity. Result: The EZL-PNs-opt formulation showed 616 ± 13.21 nm of vesicle size, and 81.21 ± 2.35% of EE. EZL-PNs-opt exhibited negative zeta potential and spherical confirmed scanning electron microscopy. EZL-PNs-opt showed sustained release of EZL (95.07 ± 2.10% in 12 h) than pure EZL dispersion. The ex-vivo gut permeation result exhibited a significantly (p < 0.05) enhanced flux than pure EZL. The in vivo results revealed 4.02-fold enhancement in bioavailability and 61.65% protection in ulcer than pure EZL dispersion (43.82%). Conclusion: Our findings revealed that EZL-PNs formulation could be an alternative delivery system of EZL to enhance oral bioavailability and antiulcer activity.     

量子体系的相空间规范变换

外尔于1918年引入的规范变换实际上是相位变换而非真正的尺度变换,但规范不变性、规范理论等概念都沿袭了下来。我们发现,针对由量子化条件[x, p]=iℏ而来的量子体系之本征值问题存在规范变换,或者说尺度变换,x → x/α,p → αp,该变换保体系的能量谱不变。量子谐振子、氢原子问题及一类多体问题的精确解析解证实了这一点。量子化条件 [x, p]=iℏ看来是个对量子力学很强的约束,不止于能量的量子化。这个规范变换提醒我们相空间的体积及其量子化才是物理的关键,这也是量子力学和统计物理在潜意识里一直沿用却未予关注的思路。有趣的是,从量子谐振子体系的相空间表述似乎不能导向这个结论。如同规范理论所断言的电磁学量在给定坐标系下的数值表征与标度无关,我们认为量子体系的物理量,如能量谱等,在给定坐标系下的数值表征亦应与标度无关。此尺度变换与德布罗意关系相恰。     

Existence of strong minimizers for the Griffith static fracture model in dimension two

We consider the Griffith fracture model in two spatial dimensions, and prove existence of strong minimizers, with closed jump set and continuously differentiable deformation fields. One key ingredient, which is the object of the present paper, is a generalization to the vectorial situation of the decay estimate by De Giorgi, Carriero, and Leaci. This is based on replacing the coarea formula by a method to approximate $SB{D}^p$ functions with small jump set by Sobolev functions, and is restricted to two dimensions. The other two ingredients will appear in companion papers and consist respectively in regularity results for vectorial elliptic problems of the elasticity type and in a method to approximate in energy $GSB{D}^p$ functions by $SB{V}^p$ ones.     

Extreme beam attenuation in double-slit experiments: Quantum and subquantum scenarios

Combining high and low probability densities in intensity hybrids  , we study some of their properties in double-slit setups. In particular, we connect to earlier results on beam attenuation techniques in neutron interferometry and study the effects of very small transmission factors, or very low counting rates, respectively, at one of the two slits. We use a “superclassical” modeling procedure which we have previously shown to produce predictions identical with those of standard quantum theory. Although in accordance with the latter, we show that there are previously unexpected new effects in intensity hybrids for transmission factors below a?10⁻⁴$a?10^{-4}$, which can eventually be observed with the aid of weak measurement techniques. We denote these as quantum sweeper effects, which are characterized by the bunching together of low counting rate particles within very narrow spatial domains. We give an explanation of this phenomenology by the circumstance that in reaching down to ever weaker channel intensities, the nonlinear nature of the probability density currents becomes ever more important, a fact which is generally not considered–although implicitly present–in standard quantum mechanics.     

用量子力学研究膦化三氢化铝储氢材料在磷化氢催化作用下的释氢反应机理

利用量子力学第一原理研究了储氢材料膦化三氢化铝(AlH3PH3)在催化剂膦(PH3)作用下的释氢反应机理;首先在MP2/aug-cc-pVDZ水平上计算了反应物、过渡态和产物的几何构型和频率,进而利用内禀反应坐标理论确定了反应的最小能量路径,随后在CCSD(T)/aug-cc-pVDZ水平上对基于MP2优化的几何构型进行了能量校正.结果表明,AlH3PH3释氢的能垒高于Al―P键的离解能,而催化剂PH3不能降低AlH3PH3的释氢能垒.因此,需要寻找其他的催化剂以使AlH3PH3成为一种合用的储氢材料.     

Water PMF for predicting the properties of water molecules in protein binding site

Water is an important component in living systems and deserves better understanding in chemistry and biology. However, due to the difficulty of investigating the water functions in protein structures, it is usually ignored in computational modeling, especially in the field of computer‐aided drug design. Here, using the potential of mean forces (PMFs) approach, we constructed a water PMF (wPMF) based on 3946 non‐redundant high resolution crystal structures. The extracted wPMF potential was first used to investigate the structure pattern of water and analyze the residue hydrophilicity. Then, the relationship between wPMF score and the B factor value of crystal waters was studied. It was found that wPMF agrees well with some previously reported experimental observations. In addition, the wPMF score was also tested in parallel with 3D‐RISM to measure the ability of retrieving experimentally observed waters, and showed comparable performance but with much less computational cost. In the end, we proposed a grid‐based clustering scheme together with a distance weighted wPMF score to further extend wPMF to predict the potential hydration sites of protein structure. From the test, this approach can predict the hydration site at the accuracy about 80% when the calculated score lower than ?4.0. It also allows the assessment of whether or not a given water molecule should be targeted for displacement in ligand design. Overall, the wPMF presented here provides an optional solution to many water related computational modeling problems, some of which can be highly valuable as part of a rational drug design strategy. © 2012 Wiley Periodicals, Inc.     

From Dislocation Motion to an Additive Velocity Gradient Decomposition, and Some Simple Models of Dislocation Dynamics

A mathematical theory of time-dependent dislocation mechanics of unrestricted geometric and material nonlinearity is reviewed. Within a ``small deformation" setting, a suite of simplified and interesting models consisting of a nonlocal Ginzburg Landau equation, a nonlocal level set equation, and a nonlocal generalized Burgers equation is derived. In the finite deformation setting, it is shown that an additive decomposition of the total velocity gradient into elastic and plastic parts emerges naturally from a micromechanical starting point that involves no notion of plastic deformation but only the elastic distortion, material velocity, dislocation density and the dislocation velocity. Moreover, a plastic spin tensor emerges naturally as well.     

Compression testing of continuous fiber reinforced polymer composites with out-of-plane fiber waviness and circular notches

We investigated the face-stabilized Open-Hole Compression (OHC) test method for evaluating the effects of fiber waviness on the compression strength of continuous carbon fiber reinforced polymer composites. Temporal evaluations of the load-deformation response, acoustic emissions and optical microscopy are used to understand the failure modes and damage progression in the OHC specimen. The failure modes observed are structurally correlated to matrix failure and kink zone formation leading to fiber fracture. The results show how the resin pocket plays a more critical role than the layup in influencing the initiation of damage in the composite specimens.