Characterizing scale dependence of effective diffusion driven by fluid flows

We study the scale dependence of effective diffusion of fluid tracers, specifically, its dependence on the P\'{e}clet number, a dimensionless parameter of the ratio between advection and molecular diffusion. Here, we address the case that length and time scales on which the effective diffusion can be described are not separated from those of advection and molecular diffusion. For this, we propose a new method for characterizing the effective diffusivity without relying on the scale separation. For a given spatial domain inside which the effective diffusion can emerge, a time constant related to the diffusion is identified by considering the spatio-temporal evolution of a test advection-diffusion equation, where its initial condition is set at a pulse function. Then, the value of effective diffusivity is identified by minimizing the $L_\infty$ distance between solutions of the above test equation and the diffusion one with mean drift. With this method, for time-independent gyre and time-periodic shear flows, we numerically show that the scale dependence of the effective diffusivity changes beyond the conventional theoretical regime. Their kinematic origins are revealed as the development of the molecular diffusion across flow cells of the gyre and as the suppression of the drift motion due to a temporal oscillation in the shear.Comment: 10 pages, 4 figure

極低温磁化・比熱測定で探る擬一次元磁性体の量子臨界現象

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 瀧川 仁, 東京大学教授 金道 浩一, 東京大学教授 福山 寛, 東京大学教授 小形 正男, 東京大学准教授 村川 智University of Tokyo(東京大学

極低温磁化・比熱測定で探る擬一次元磁性体の量子臨界現象

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 瀧川 仁, 東京大学教授 金道 浩一, 東京大学教授 福山 寛, 東京大学教授 小形 正男, 東京大学准教授 村川 智University of Tokyo(東京大学

Identification of a Novel Deactivating Small-Molecule Compound for Fibrogenic Hepatic Stellate Cells

Background: Liver fibrosis progresses to decompensated liver cirrhosis, for which medical needs remain unmet. We recently developed IC-2, a small-molecule compound that suppresses Wnt/β-catenin signaling, and found that IC-2 also suppresses liver fibrosis. In this study, we performed three-step screening of newly synthesized IC-2 derivatives to identify other small-molecule compounds that suppress liver fibrosis. Methods: The screening system consisted of three steps: a cell viability assay, a transcription factor 4 (TCF4) reporter assay, and induction of α-smooth muscle actin (α-SMA) and collagen 1α1 (Col1A1) expression in response to each compound. Screening using human LX-2 hepatic stellate cells (HSCs) was performed to target HSCs, which are the driver cells of liver fibrosis. Results: In the first step, since 9b and 9b-CONH2 at 100 μM did not have any effects on cell viability, they were omitted in the next screening. Additionally, the conditions that led to > 40% inhibition of the controls were also excluded in subsequent screening. The second step was performed under 31 conditions for 19 small-molecule compounds. Sixteen small-molecule compounds caused significant reduction of TCF4 activity relative to that of 0.1% DMSO. Of the 16 compounds, the 10 showing the greatest suppression of TCF4 activity were selected for the third step. Expressions of mRNA for α-SMA and Col1A1 were significantly reduced by seven and three small-molecule compounds, respectively. The greatest reductions in the α-SMA and Col1A1 mRNA expressions were observed in the cells treated with IC-2-F. Protein expressions of α-SMA and Col1A1 caused by IC-2-F were also comparable to those caused by IC-2. Conclusion: IC-2-F was identified as a novel deactivating small-molecule compound for HSCs in vitro. These data suggest that IC-2-F is a promising medicine for liver fibrosis