Benign preparation of aqueous core poly lactic-co-glycolic acid (PLGA) microcapsules.

Poly lactic-co-glycolic acid (PLGA) has attracted considerable attention as a polymer for drug delivery carriers. However, the hydrophobic property of PLGA often leads to the use of harmful organic solvents and poor encapsulation efficiency of hydrophilic materials. To our knowledge, a preparation method of aqueous core PLGA microcapsules without using harmful organic solvents has not been proposed. In this study, we attempted to establish an encapsulation technique of hydrophilic materials in aqueous core biodegradable and biocompatible PLGA microcapsules using vegetable oil as a continuous phase. As a result, the temperature of the oil/water mixture was required to be above the glass transition temperature. In this condition, two different types of morphology were prepared. When the water volume was below the solubility limit, PLGA microcapsules with a smooth shell were formed. In contrast, when the water volume was above the solubility limit, colloidosome-like microcapsules with PLGA nanoparticles assembled at the interface were formed. The obtained microcapsules were then heated at the glass transition temperature. The result is that aqueous core PLGA microcapsules with a smooth shell were prepared using plant oil as a continuous phase. Rhodamine B used as a hydrophilic model encapsulant, was successfully encapsulated in the PLGA microcapsules

An inertial range length scale in structure functions

It is shown using experimental and numerical data that within the traditional inertial subrange defined by where the third order structure function is linear that the higher order structure function scaling exponents for longitudinal and transverse structure functions converge only over larger scales, $r>r_S$, where $r_S$ has scaling intermediate between $\eta$ and $\lambda$ as a function of $R_\lambda$. Below these scales, scaling exponents cannot be determined for any of the structure functions without resorting to procedures such as extended self-similarity (ESS). With ESS, different longitudinal and transverse higher order exponents are obtained that are consistent with earlier results. The relationship of these statistics to derivative and pressure statistics, to turbulent structures and to length scales is discussed.Comment: 25 pages, 9 figure

Statins prevent pulsatile stretch-induced proliferation of human saphenous vein smooth muscle cells via inhibition of Rho/Rho-kinase pathway

Objective: Pulsatile forces regulate vascular remodeling and trigger vascular diseases such as saphenous vein graft disease. The saphenous vein is exposed to high pressure and pulsatility only after implantation. Statins have been proved to reduce the incidence of vein graft failure. Thus, we investigated the molecular mechanisms of pulsatile stretch-induced saphenous vein smooth muscle cell (SMC) proliferation and potential beneficial effects of statins. Methods and results: Human saphenous vein SMCs were subjected to cyclic stretch (60 cycles/min) in Flex I plates. Cerivastatin and simvastatin significantly prevented stretch-induced increase in SMC proliferation. Stretch induced the membrane accumulation of Rho A and Rho kinase inhibitors (Y-27632 and hydroxyfasudil) and dominant negative Rho A mutant significantly prevented stretch-induced SMC proliferation. In addition, stretch increased the levels of both p44/42 mitogen-activated protein (MAP) kinase and Akt phosphorylation. MAP kinase kinase (MEK)1/2 inhibitor U0126, phosphatidylinositol (PI) 3-kinase inhibitors (wortmaninn and LY294002), and dominant negative Akt mutant significantly prevented stretch-induced SMC proliferation. Cerivastatin significantly prevented stretch-induced membrane accumulation of Rho A. On the other hand, stretch-induced phosphorylation of p44/42 MAP kinase and Akt was not prevented by cerivastatin. Mevalonate restored the preventive effect of cerivasatain on stretch-induced Rho A membrane accumulation. Stretch induced hyperphosphorylation of retinoblastoma protein (pRb), which was prevented by cerivastatin and the Rho kinase inhibitors. Conclusion: Statins prevent stretch-induced saphenous vein SMC proliferation via inhibition of the Rho/Rho-kinase pathway. This may explain the beneficial effects of this class of drug, especially for patients after coronary artery bypass graftin

Felodipine inhibits nuclear translocation of p42/44 mitogen-activated protein kinase and human smooth muscle cell growth

Objective: Smooth muscle cell (SMC) proliferation contributes to vascular structural changes in cardiovascular disease. Ca2+ antagonists exert antiproliferative effects and may also be clinically beneficial in the patients. However, the underlying mechanisms of action remain elusive. Activation of mitogen-activated protein kinases (MAPK), in particular p42/44mapk plays a central role in cell proliferation. We hypothesise that Ca2+ antagonists inhibit cell proliferation by interfering with the p42/44mapk pathway in human SMC. Methods: SMC were cultured from human aorta. Cell proliferation was analysed by [3H]thymidine incorporation. Activation of p42/44mapk and the nuclear target protein Elk-1 was analysed by phosphorylation and p42/44mapk nuclear translocation by confocal microscope. Results: PDGF-BB (10 ng/ml) stimulated [3H]thymidine incorporation, phosphorylated p42/44mapk, caused nuclear translocation of the enzymes and phosphorylated the nuclear target protein Elk-1. Felodipine (10−7 to 10−5 mol/l) inhibited [3H]thymidine incorporation to PDGF-BB, had no effect on p42/44mapk phosphorylation. However, p42/44mapk nuclear translocation and Elk-1 activation stimulated by PDGF-BB were prevented by the Ca2+ antagonist. Conclusion: Activation of p42/44mapk, subsequent nuclear translocation and activation of Elk-1 are essentially associated with human SMC proliferation. The Ca2+ antagonist felodipine prevents p42/44mapk nuclear translocation (but not its activation) associated with inhibition of human SMC growt

Effects of small Hsp genes on developmental stability and microenvironmental canalization

Background: Progression of development has to be insulated from the damaging impacts of environmental and genetic perturbations to produce highly predictable phenotypes. Molecular chaperones, such as the heat shock proteins (HSPs), are known to buffer various environmental stresses, and are deeply involved in protein homeostasis. These characteristics of HSPs imply that they might affect developmental buffering and canalization. Results: We examined the role of nine Hsp genes using the GAL4/UAS-RNAi system on phenotypic variation of various morphological traits in Drosophila melanogaster. The stability of bristle number, wing size and wing shape was characterized through fluctuating asymmetry (FA) and the coefficient of variation (CV), or among-individual variation. Progeny of the GAL4/Hsp-RNAi crosses tended to have reduced trait means for both wing size and wing shape. Transcriptional knockdown of Hsp67Bc and Hsp22 significantly increased FA of bristle number, while knockdown of Hsp67Ba significantly increased FA and among-individual variation of wing shape but only in males. Suppression of Hsp67Bb expression significantly increased among-individual variation of bristle number. The knockdown of gene expression was confirmed for Hsp67Ba, Hsp67Bc, Hsp22, and Hsp67Bb. Correlation between FA and CV or among-individual variation of each trait is weak and not significant except for the case of male wing shape. Conclusion: Four small Hsp genes (Hsp22, Hsp67Ba, Hsp67Bb and Hsp67Bc) showed involvement in the processes of morphogenesis and developmental stability. Due to possible different functions in terms of developmental buffering of these small Hsps, phenotypic stability of an organism is probably maintained by multiple mechanisms triggered by different environmental and genetic stresses on different traits. This novel finding may lead to a better understanding of non-Hsp90 molecular mechanisms controlling variability in morphological traits

Convergence of the Gaussian Expansion Method in Dimensionally Reduced Yang-Mills Integrals

We advocate a method to improve systematically the self-consistent harmonic approximation (or the Gaussian approximation), which has been employed extensively in condensed matter physics and statistical mechanics. We demonstrate the {\em convergence} of the method in a model obtained from dimensional reduction of SU($N$) Yang-Mills theory in $D$ dimensions. Explicit calculations have been carried out up to the 7th order in the large-N limit, and we do observe a clear convergence to Monte Carlo results. For $D \gtrsim 10$ the convergence is already achieved at the 3rd order, which suggests that the method is particularly useful for studying the IIB matrix model, a conjectured nonperturbative definition of type IIB superstring theory.Comment: LaTeX, 4 pages, 5 figures; title slightly changed, explanations added (16 pages, 14 figures), final version published in JHE

Non-thermal Leptogenesis and a Prediction of Inflaton Mass in a Supersymmetric SO(10) Model

The gravitino problem gives a severe constraint on the thermal leptogenesis scenario. This problem leads us to consider some alternatives to it if we try to keep the gravitino mass around the weak scale $m_{3/2} \sim 100$ GeV. We consider, in this paper, the non-thermal leptogenesis scenario in the framework of a minimal supersymmetric SO(10) model. Even if we start with the same minimal SO(10) model, we have different predictions for low-energy phenomenologies dependent on the types of seesaw mechanism. This is the case for leptogenesis: it is shown that the type-I see-saw model gives a consistent scenario for the non-thermal leptogenesis but not for type-II. The predicted inflaton mass needed to produce the observed baryon asymmetry of the universe is found to be $M_I \sim 5 \times 10^{11}$ GeV for the reheating temperature $T_R = 10^6$ GeV.Comment: 9 pages, 2 figures; the version to appear in JCA

Positronium reemission yield from mesostructured silica films

The reemission yield of ortho-positronium (o-Ps) into vacuum outside mesoporous silica films on glass is measured in reflection mode with a specially designed lifetime (LT) spectrometer. Values as high as 40% are found. The intensity of the 142 ns vacuum LT is recorded as a function of reemission depth. The LT depth profiling is correlated to the 2gamma and 3gamma energy ones to determine the annihilation characteristics inside the films. Positron lifetime in capped films is used to determine the pore size. For the first time, a set of consistent fingerprints for Ps annihilation, o-Ps reemission into vacuum, and pore size, is directly determined in CTACl-TEOS films

Pattern formation of reaction-diffusion system having self-determined flow in the amoeboid organism of Physarum plasmodium

The amoeboid organism, the plasmodium of Physarum polycephalum, behaves on the basis of spatio-temporal pattern formation by local contraction-oscillators. This biological system can be regarded as a reaction-diffusion system which has spatial interaction by active flow of protoplasmic sol in the cell. Paying attention to the physiological evidence that the flow is determined by contraction pattern in the plasmodium, a reaction-diffusion system having self-determined flow arises. Such a coupling of reaction-diffusion-advection is a characteristic of the biological system, and is expected to relate with control mechanism of amoeboid behaviours. Hence, we have studied effects of the self-determined flow on pattern formation of simple reaction-diffusion systems. By weakly nonlinear analysis near a trivial solution, the envelope dynamics follows the complex Ginzburg-Landau type equation just after bifurcation occurs at finite wave number. The flow term affects the nonlinear term of the equation through the critical wave number squared. Contrary to this, wave number isn't explicitly effective with lack of flow or constant flow. Thus, spatial size of pattern is especially important for regulating pattern formation in the plasmodium. On the other hand, the flow term is negligible in the vicinity of bifurcation at infinitely small wave number, and therefore the pattern formation by simple reaction-diffusion will also hold. A physiological role of pattern formation as above is discussed.Comment: REVTeX, one column, 7 pages, no figur