关键词： Nanoparticles   Nanosuspension   Intestinal absorption   Permeability   Modelling   Biopharmaceutics   Colloidal structures  

摘要： Particle size reduction is a traditional approach to increase the intestinal absorption of active pharmaceutical ingredients with poor intestinal solubility, by increasing the particle dissolution rate. However, an increase in the dissolution rate cannot always fully explain the effects of nanoformulations, and a method of assessing the potential benefits of a nanoformulation in vivo would hence be of great value in drug development. A novel mathematical model of a nanoformulation, including interlinked descriptions of the hydrodynamics, particle dissolution and diffusion of particles and colloidal structures (CS), was developed to predict the combined in vivo effects of these mechanisms on drug absorption. The model successfully described previously reported in vivo observations of nanoformulated aprepitant in rats, at various drug concentrations and in the presence or absence of CS. The increase in absorption rate was explained as a direct consequence of the increased drug concentration at the membrane, caused by the contributing effects of the diffusion of both nanoparticles and CS into which the drug had partitioned. Further simulations supported the conclusion that the model can be applied during drug development to provide a priori assessments of the potential benefits of nanoformulations.

ISBN: (纸本)9787568047869

关键词： Free energy   QM/MM   Molecules   Solvents   Hydration  

摘要： The solvation of carbon dioxide in solution represents a key step for the capture and fixation CO2 in nature, which may be further influenced by the formation of (bi)carbonate species and/or the formation of CO2 clusters in solution. The latter processes are strongly dependent on the exact environment of the liquid state (e.g., pH value, solvated ions, etc.) and may interfere with the experimental determination of structural, dynamical, and thermodynamic properties. In this work a hybrid quantum mechanical/molecular mechanical (QM/MM) simulation approach at correlated ab initio level of theory resolution-of-identity second-order Moller-Plesset Perturbation Theory (RI-MP2) has been applied in the framework of thermodynamic integration (TI) to study structure, dynamics, and the hydration free energy of a single carbon dioxide molecule in aqueous solution. A detailed analysis of the individual QM/MM potential energy contributions demonstrate that the overall potential remains highly consistent over the entire sampling phase and that no artificial contributions are influencing the determination of the hydration free energy. The latter value of 0.01 +/- 0.92 kcal/mol was found in very good agreement with the values of 0.06 and 0.24 kcal/mol obtained via quasi-chemical theory and experimental measurements, respectively. In order to obtain detailed information about the C- and O-c-water interaction, conically restricted regions with respect to the main axis of the CO2 molecule have been employed in structural analysis. The presented data not only provide detailed information about the hydration properties of CO2 but act as a critical validation of the simulation technique, which will be beneficial in the study of nonaqueous solvents such as pure and aqueous NH3 solutions, which have been suggested as potential candidates to capture CO2 from anthropogenic sources.

关键词： alpha-Glucosidase   Flavonoid   Geraniaceae   Geranium asphodeloides   Tannin  

摘要： Some Geranium species have been used to treat diabetes. To evaluate the scientific basis of this ethnopharma-cological use, we aimed to isolate potent alpha-glucosidase inhibitory metabolites of Geranium asphodeloides Burm. through in vitro bioactivity-guided fractionation. All the tested extracts showed high alpha-glucosidase inhibitory effect compared to acarbose. Among the tested extracts, the ethyl acetate subextract showed the highest activity with an IC50 value of 0.85 +/- 0.01 mu M. A hydrolysable tannin, 1,2,4 tri-O-galloyl-beta-D-glucopyranose (1), and five flavonoid glycosides, kaempferol-3-O-alpha-rhamnopyranoside (2), kaempferol-3-O-alpha-rabinofuranoside (3), quercetin-3-O-beta-glucopyranoside (4), quercetin-3-O-alpha-rhamnopyranoside (5), and quercetin-3-O-alpha-rhamnofuranoside (6), were isolated from the ethyl acetate subextract. Their structures were identified by 1D- and 2D-NMR experiments. 1 exhibited the highest alpha-glucosidase inhibitory effect, approximately 61 times more potent than positive control, acarbose, with an IC50 value of 0.95 +/- 0.07 mu M. Also, 2 was more potent than acarbose. An enzyme kinetics analysis revealed that compounds 2, 3 and 4 were competitive, whereas 1 and 6 uncompetitive inhibitors. Molecular docking studies were performed to get insights into inhibition mechanisms of the isolated compounds in the light of the enzyme kinetic studies using various binding sites of the enzyme model.

关键词： Graphene oxide (GO)   Cement composites   Hydration   Pore structure   Calcium silicate hydrate (C-S-H) gels  

摘要： The effects of graphene oxide (GO) on the hydration kinetics, pore structure, mechanical properties, and the structure of calcium silicate hydrate (C-S-H) gels were systematically investigated by combinatorial techniques. GO can accelerate the cement hydration, refine the pore structure and increase the polymerization degree of C-S-H gels due to the nucleation effects of GO. The specific surface area of cement paste and the number of gel pores were reduced with the addition of GO. A 3D network structure of GO modified C-S-H gels was originally proposed based on the obtained results that GO could intercalate into the interlayer space of C-S-H gels through ionic bonding with Ca2+ and fill in the gel pores. A small fraction of GO (0.022 wt%) increased the 28 d compressive strength by 16.31%-25.60% at a various water to cement ratios, indicating that GO is a potential nano-reinforcing material for cement composites. The results would provide a well understanding of the reinforcing mechanisms of GO in cement composites and pave a pathway for the design of high-performance cement composites. (C) 2018 Elsevier Ltd. All rights reserved.

摘要： Several regimes of motion are evident in red blood cells (RBCs) under shear flow and are known to be controlled by the shear flow rate and by the deformability of the cell. Above a certain shear flow rate, healthy RBCs present a fluidized regime analogous to that of a droplet: the membrane adopts a tank-treading motion, i.e. rotates around the centre of mass of the cell, and its orientation oscillates around a mean value (Fig. 1). This motion is not observed in rigid RBCs which keep the same regime of motion as with low shear flow rate. The transition from one motion to the other depends on several intrinsic parameters including membrane viscosity, elasticity and cytoplasmic viscosity. Sickle cell disease (SCD) is a hereditary hemolytic anemia due to the presence of mutant hemoglobin, Hb S, which tends to polymerize in RBCs, reducing its deformability and resulting ultimately in RBC sickling. We postulate that SCD may affect RBCs capacity to adopt the tank-treading motion. Thanks to microfluidic chips coupled with high speed video, we studied the fraction of RBCs displaying a tank-treading motion (% of TT) at moderate shear stresses (0.4-0.6 Pa), in homozygous SCD patients (n=30) and in normal subjects (n=12). At the time of sampling, SCD patients were in steady state (no vaso-occlusive crisis or other acute complications) and not transfused for at least 3 months. Around 3 microL of total blood were necessary for each measurement. RBCs were studied under atmospheric conditions and exhibited the normal discoid shape. We showed first that the % of TT is significantly different in SCD patients compared to controls, with no overlap between the values of each groups (respectively 70.4±12.9% versus 98.6±0.9%). Second, measurements performed on different cells fractions isolated by cell density or in the presence of different NaCl concentrations, showed that the % of TT cells is sensitive to cell density and hydration status, both in normal subjects and in SCD patients. Fi

关键词： Bark beetle   Ips   Disturbance interaction   Picea abies   Wind disturbance   Root rot  

摘要： Interaction of disturbance agents may cause cascading effects in forests. The three most important disturbance agents of Norway spruce (Picea abies) in northern Europe are Heterobasidion root rot, wind and the European spruce bark beetle (Ips typographus). In this study, we present a mechanistic individual agent based model to simulate the dynamics of the bark beetle and integrate it in the simulation framework WINDROT to further study the interactive dynamics of root rot, wind and bark beetles. We carried out model performance analysis concluding that the model is sensitive to the parameters of optimal bark thickness for reproduction. Stand level interaction between wind and bark beetle disturbances was also evaluated against field data. The stand level simulations show the interaction between the disturbance agents;the root rot increases wind disturbance and bark beetles benefit from wind fallen trees. No direct interaction was found in the simulation study between the root rot and bark beetles. Further experimental research and large scale simulation studies are needed to better understand the underlying mechanisms in the interaction between the disturbance agents.

关键词： C3S   C-S-H   Nano-indentation   SEM/EDX/BSE   Ca/Si ratio   Molecular dynamics  

摘要： Calcium silicate hydrate (C-S-H) is the most important hydration product in cementitious material. Due to its complexity, the investigation on its mechanical properties is still in progress. In this study, synthesized C3S was utilized to produce relatively pure C-S-H gels with two different water/solid ratios. Then mechanical properties of the C-S-H were measured and characterized by nano-indentation and SEM/EDX/BSE. Two types of C-S-H with Ca/Si ratio around 1.8 were observed through statistical analysis of the indentation modulus (Er) and hardness (H). The looser one possessing lower Er around 25-30 GPa while the denser one possesses higher Er of 35.9 GPa. Both phases have higher stiffness than those of high density (HD) and low density (LD) phase obtained from cement pastes. Furthermore, molecular dynamics provides mechanical understanding of C-S-H gel at nano-scale. Based on the crystal structure of tobermorite 11 angstrom, 64 models with Ca/Si ratios from 1.3 to 2.0 were constructed for uniaxial tension test. The stiffness and cohesive strength of the C-S-H gel are greatly influenced by Ca/Si ratio, water content and nano-porosity. With increasing Ca/Si ratio from 1.3 to 2.0, long silicate chains were broken to shorter ones and more water molecules penetrated into defect regions. The destroyed silicate skeleton and the "hydrolytic weakening" effect resulted in the reduction of the mechanical properties of C-S-H gels. Concurrently considering the intrinsic porosity and chemical compositions, the appropriate micromechanical models are utilized to upscale the molecular properties to higher level. (C) 2018 Elsevier Ltd. All rights reserved.

关键词： Viscosity   Density   Mechanical seal   Ferrofluids   Spiral groove  

摘要： Purpose The purpose of this study is to investigate the hydrodynamic lubrication characteristics of ferrofluid film for spiral groove mechanical seal in external electromagnetic field and to analyze the effects of the volume fraction of ferrofluid, parameters of the electromagnetic field, operating parameters and geometrical parameters of mechanical seal on the characteristics of ferrofluid film. Design/methodology/approach The relationship between the ferrofluid viscosity and the intensity of external electromagnetic field was established. Based on the Muijderman narrow groove theory, the pressure distribution was calculated with the trial method by trapezoid formula. Findings It was found that pressure, average viscosity, average density and opening force of ferrofluid between end faces increase with the increase in intensity of current, volume fraction of ferrofluid, rotating speed, pressure differential and spiral angle;decrease with the increase in temperature;and increase at first and then decrease with the increase in the ratio of groove width to weir and the groove length. All of them reach the maximum value when the ratio of width of groove to weir is 0.7 and the ratio of groove length is 0.6. Leakage of ferrofluid increases with an increase in intensity of current, volume fraction of ferrofluid, rotating speed, pressure differential, spiral angle and ratio of groove length;decreases with an increase in temperature;and increases at first and then decreases with the increase in the ratio of groove width to weir. The tendencies of characteristics of silicone oil are consistent with those of ferrofluid, and the characteristics of silicone oil are smaller than those of ferrofluid under the same condition. Originality/value The volume fraction of ferrofluid, rotating speed, spiral angle, ratio of groove width to weir, groove length and temperature have a significant influence on the characteristics of ferrofluid film;however, intensity of current and the pressur

关键词： Vegetables  

摘要： As a new type of machine, field vegetable power machinery can realize different pre-harvest mechanization operations. The frame is subjected to various loads during field operations, which is accompanied by dynamic load. It is necessary to carry out strength research and optimization design of the frame. The multi-objective topology optimization design method based on field measured strain data was studied. HyperWorks software was used to carry out finite element analysis of the frame, the stress distribution under static stress analysis conditions was obtained, and the fatigue damage hotspot of the frame was determined. On the basis of data analysis, the strain gauges were pasted, and the dynamic strain test system was set up to collect the load time history under typical working conditions of field vegetable power machinery. The measured strain time history data was preprocessed, and the force of the frame under the corresponding working conditions was analyzed. The load spectrum was compiled by nCode software, and the fatigue analysis and life prediction of the frame were performed. Based on the analysis and life prediction, the topology optimization was proposed, and a multi-objective topology optimization mathematical model with multiple frame conditions and dynamic low-order natural frequency response was constructed to carry out lightweight design. The test results showed that the fatigue life at the cross weld of the frame was 7.5×104 h, the fatigue life was the shortest among the 15 points, which met the service life requirement, and the overall structural strength of the frame was over-designed. The optimized frame quality was reduced by 443.55 kg, which was reduced by 53.47%. © 2018, Chinese Society of Agricultural Machinery. All right reserved.