The Development of an In Vitro Horizontal Diffusion Cell to Monitor Nasal Powder Penetration Inline

The development of in vitro investigation models could be important using sensitive and fast methods during formulation. Intranasal applied drugs (meloxicam, lamotrigine, and levodopa) avoid the gastrointestinal tract and can achieve higher bioavailability, therefore a penetration extent is a key property. In this study, the in vitro adaptability of a modified horizontal diffusion cell was tested by using these model active pharmaceutical ingredients (APIs). The special factors consisted of the volume of the chambers, the arrangement of the stirrers, the design of probe input for real-time analysis and decreased membrane area. Membranes were impregnated by isopropyl myristate and by using phosphate buffer to evaluate the effect of API hydrophilicity on the diffusion properties. The lipophilicity of the API was proportional to the penetration extent through isopropyl myristate-impregnated membranes compared with buffer-soaked membranes. After evaluating the arithmetic mean of standard relative deviations and the penetrated extent of APIs at 15 min, Metricel® could be suggested for levodopa and meloxicam, and Whatman™ for lamotrigine. The modified model is suitable for inline, real-time detection, at nasal conditions, using small volumes of phases, impregnated membrane, to monitor the diffusion of the drug and to determine its concentration in the acceptor and donor phases.

A New Horizontal Mixing-Length Formulation for Numerical Simulations of Tropical Cyclones

A new physically-based horizontal mixing-length formulation is introduced and evaluated in the Hurricane Weather and Research Forecast (HWRF) model. Recent studies have shown that the structure and intensity of tropical cyclones (TCs) simulated by numerical models are sensitive to horizontal mixing length in the parameterization of horizontal diffusion. Currently, many numerical models including the operational HWRF model formulate the horizontal mixing length as a fixed fraction of grid spacing or a constant value, which is not realistic. To improve the representation of the horizontal diffusion process, the new formulation relates the horizontal mixing length to local wind and its horizontal gradients. The resulting horizontal mixing length and diffusivity are much closer to those derived from field measurements. To understand the impact of different mixing-length formulations, we analyze the evolutions of an idealized TC simulated by the HWRF model with the new formulation and with the current formulation (i.e., constant values) of horizontal mixing length. In two real-case tests, the HWRF model with the new formulation produces the intensity and track forecasts of Hurricanes Harvey (2017) and Lane (2018) that are much closer to observations. Retrospective runs of hundreds of forecast cycles of multiple hurricanes show that the mean errors in intensity and track simulated by HWRF with the new formulation can be reduced approximately by 10%.

Numerical Analysis of the Hydrogen Dispersion Behavior in Different Directions in a Naturally Ventilated Space

Studies on hydrogen leakage have mainly focused on the influences of location and geometrical configuration on the distribution of the hydrogen in various spaces. The present study developed a simplified model for the leakage diffusion of hydrogen in an enclosed cuboid space with two vents, at the top and at the bottom, respectively. The effect of different leakage positions on the diffusion of the hydrogen was analyzed. The results showed that when hydrogen diffused vertically from the bottom to the top of the space, the farther the leakage position was from the vent on the side wall, the more hydrogen accumulated. When the hydrogen leaked in the vertical direction from the floor, the distance between the leakage position and the bottom vent had little effect on the horizontal diffusion speed of the hydrogen at the top of the space. The diffusion speed for the leakage in the horizontal direction was faster than that in the vertical direction. When the hydrogen leaked in the horizontal direction from the side wall, the height of the leakage had little effect on the horizontal diffusion speed of the hydrogen at the top of the space. Stratification occurred for models set up in the present study whenever the envelope of 1% mole fraction, or 4% mole fraction, of hydrogen extended to the whole ceiling.

Direct democracy, policy diffusion, and medicalized marijuana

Virtually all studies of policy diffusion are based on statutory enactments by state legislatures. But a substantial number of medicalized marijuana laws were initiated through citizen initiatives and ratified by referenda (I&R). This case study suggests that the diffusion of laws adopted by I&R requires two modifications to the conventional model of policy diffusion. First, early policy adoptions must occur through direct democracy so that horizontal diffusion results when those past adoptions by the I&R process lead to future adoptions. Second, the necessity of bypassing institutions of representative government must be operationalized as an interaction between the availability of direct democracy and the precise political variable that blocks legislative enactments.

Calculative Width of Pile Foundation on Slope Based on Particle Image Velocimetry (PIV)

The calculative width directly affecting the horizontal bearing capacity of the pile is an important parameter of the horizontal loaded pile foundation and its effective value will change with the variation of slope angle. In order to research the effect of slope on calculative width, 4 groups of model test under static lateral loading with different slope angles were carried out indoor. Based on the PIV system, the horizontal diffusion angle was obtained by the quantitative analysis of the vectorial displacement field of soil around the pile. The calculative width of pile under 4 slopes was then calculated based on the Horizontal Diffusion Principle. Compared with numerical simulation and full-scale test, calculative width based on Horizontal Diffusion Principle is greater than that based on the code of China (JGJ94-2008) and it decreases by about 3.3 m by every 10° increase of slope. After correcting the calculative width based on Horizontal Diffusion Principle, m-value that can characterize the horizontal resistance of the pile is greater than that based on the code of China (JGJ94-2008); the average difference of two m-values is about 75 MN/m4. Slope has a strong weakening effect on m-value. These conclusions provide a certain reference for the selection of calculative width in engineering.

The effect of horizontal diffusion parameterization in convection-permitting REMO-NH simulations over Germany

<p><span>Moving towards convection permitting simulations up to few kilometers scale are emerging solutions to the challenge and complexities in simulating different convective phenomena especially over mountainous regions. In this study we execute sensitivity experiments with the non-hydrostatic regional climate model REMO-NH at convection permitting resolution (~3km). We use this model in three setups where different parameterization schemes for horizontal diffusion are tested. In the first setup “DIFF2” we utilize the standard 2</span><sup><span>nd</span></sup><span> order diffusion while the second setup “DIFF4” applies 4</span><sup><span>th</span></sup><span> order diffusion. The higher order has a smaller impact on larger scales so that the atmospheric fields exhibit more details, especially in regions with high convective activity. In the third setup “TURB3D”, REMO-NH runs with a new 3D Smagorinsky-type turbulence scheme instead of the artificial diffusion schemes. Though turbulent horizontal diffusion is of second order in this setup, it incorporates a spatially and temporally varying exchange coefficient so that flows with little deformation remain unaffected. The domain of the simulations driven with EURO-CORDEX boundary data covers Germany and the time integration spans the year 2006. </span></p><p><span>Selected cases reveal a better representation of convective elements in DIFF4 and TURB3D when compared with DIFF2. We cannot compare these individual cases directly to observations since REMO-NH is not a reanalysis but a climate model. However, the spatial precipitation fields deduced from DWD radar data have characteristics which are more similar to DIFF4 and TURB3D than to DIFF2. More details are resolved in DIFF4 and TURB3D since the diffusion mainly act at the smallest spatial scales resolved by the model. DIFF2 smoothes convective activity drastically so that it appears in the form of unrealistically wide convective cells. On the other hand, the statistics of precipitation (seasonal average, standard deviation and 95th percentile) show a better agreement with observations in the simulation DIFF2 and TURB3D. TURB3D appears to be the best compromise regarding the simulation of precipitations fields. However, TURB3D exhibits a warm bias in the 2m temperature field in autumn and winter. Further model development may help to overcome this issue.</span></p>