A symmetrical method to obtain shear moduli from microrheology

Passive microrheology typically deduces shear elastic loss and storage moduli from displacement time series or mean-squared displacement (MSD) of thermally fluctuating probe particles in equilibrium materials. Common data analysis methods use either Kramers-Kronig (KK) transformations or functional fitting to calculate frequency-dependent loss and storage moduli. We propose a new analysis method for passive microrheology that avoids the limitations of both of these approaches. In this method, we determine both real and imaginary components of the complex, frequency-dependent response function $\chi(\omega) = \chi^{\prime}(\omega)+i\chi^{\prime\prime}(\omega)$ as direct integral transforms of the MSD of thermal particle motion. This procedure significantly improves the high-frequency fidelity of $\chi(\omega)$ relative to the use of KK transformation, which has been shown to lead to artifacts in $\chi^{\prime}(\omega)$. We test our method on both model data and experimental data. Experiments were performed on solutions of worm-like micelles and dilute collagen solutions. While the present method agrees well with established KK-based methods at low frequencies, we demonstrate significant improvement at high frequencies using our symmetric analysis method, up to almost the fundamental Nyquist limit.Comment: 8 pages, 4 figure

モデル高分子網目からなるゲルの反応動力学および弾性-構造相関に関する研究

学位の種別:課程博士University of Tokyo(東京大学

Differential roles of prostaglandin E-type receptors in activation of hypoxia-inducible factor 1 by prostaglandin E1 in vascular-derived cells under non-hypoxic conditions

Prostaglandin E1 (PGE1), known pharmaceutically as alprostadil, has vasodilatory properties and is used widely in various clinical settings. In addition to acute vasodilatory properties, PGE1 may exert beneficial effects by altering protein expression of vascular cells. PGE1 is reported to be a potent stimulator of angiogenesis via upregulation of VEGF expression, which is under the control of the transcription factor hypoxia-inducible factor 1 (HIF-1). However, the molecular mechanisms behind the phenomenon are largely unknown. In the present study, we investigated the mechanism by which PGE1 induces HIF-1 activation and VEGF gene expression in human aortic smooth muscle cells (HASMCs) and human umbilical vein endothelial cells (HUVECs), both vascular-derived cells. HUVECs and HASMCs were treated with PGE1 at clinically relevant concentrations under 20% O2 conditions and HIF-1 protein expression was investigated. Expression of HIF- 1α protein and the HIF-1-downstream genes were low under 20% O2 conditions and increased in response to PGE1 treatment in both HUVECs and HASMCs in a dose- and time-dependent manner under 20% O2 conditions as comparable to exposure to 1% O2 conditions. Studies using EP-receptor-specific agonists and antagonists revealed that EP1 and EP3 are critical to PGE1-induced HIF-1 activation. In vitro vascular permeability assays using HUVECs indicated that PGE1 increased vascular permeability in HUVECs. Thus, we demonstrate that PGE1 induces HIF- 1α protein expression and HIF-1 activation under non-hypoxic conditions and also provide evidence that the activity of multiple signal transduction pathways downstream of EP1 and EP3 receptors is required for HIF-1 activation

The Novel Monoclonal Antibody 9F5 Reveals Expression of a Fragment of GPNMB/Osteoactivin Processed by Furin-like Protease(s) in a Subpopulation of Microglia in Neonatal Rat Brain

To differentiate subtypes of microglia (MG), we developed a novel monoclonal antibody, 9F5, against one subtype (type 1) of rat primary MG. The 9F5 showed high selectivity for this cell type in Western blot and immunocytochemical analyses and no cross‐reaction with rat peritoneal macrophages (Mφ). We identified the antigen molecule for 9F5: the 50‐ to 70‐kDa fragments of rat glycoprotein nonmetastatic melanoma protein B (GPNMB)/osteoactivin, which started at Lys170. In addition, 9F5 immunoreactivity with GPNMB depended on the activity of furin‐like protease(s). More important, rat type 1 MG expressed the GPNMB fragments, but type 2 MG and Mφ did not, although all these cells expressed mRNA and the full‐length protein for GPNMB. These results suggest that 9F5 reactivity with MG depends greatly on cleavage of GPNMB and that type 1 MG, in contrast to type 2 MG and Mφ, may have furin‐like protease(s) for GPNMB cleavage. In neonatal rat brain, amoeboid 9F5+ MG were observed in specific brain areas including forebrain subventricular zone, corpus callosum, and retina. Double‐immunοstaining with 9F5 antibody and anti‐Iba1 antibody, which reacts with MG throughout the CNS, revealed that 9F5+ MG were a portion of Iba1+ MG, suggesting that MG subtype(s) exist in vivo. We propose that 9F5 is a useful tool to discriminate between rat type 1 MG and other subtypes of MG/Mφ and to reveal the role of the GPNMB fragments during developing brain

The Molecular Outflows in the rho Ophiuchi Main Cloud: Implications For Turbulence Generation

We present the results of CO (J=3-2) and CO (J=1-0) mapping observations toward the active cluster forming clump, L1688, in the rho Ophiuchi molecular cloud. From the CO (J=3-2) and CO (J=1-0) data cubes, we identify five outflows, whose driving sources are VLA 1623, EL 32, LFAM 26, EL 29, and IRS 44. Among the identified outflows, the most luminous outflow is the one from the prototypical Class 0 source, VLA 1623. We also discover that the EL 32 outflow located in the Oph B2 region has very extended blueshifted and redshifted lobes with wide opening angles. This outflow is most massive and have the largest momentum among the identified outflows in the CO (J=1-0) map. We estimate the total energy injection rate due to the molecular outflows identified by the present and previous studies to be about 0.2 L_solar, larger than or at least comparable to the turbulence dissipation rate [~(0.03 - 0.1) L_solar]. Therefore, we conclude that the protostellar outflows are likely to play a significant role in replenishing the supersonic turbulence in this clump.Comment: 37 pages, 9 figures, accepted for publication in The Astrophysical Journa

Versatile whole-organ/body staining and imaging based on electrolyte-gel properties of biological tissues

Whole-organ/body three-dimensional (3D) staining and imaging have been enduring challenges in histology. By dissecting the complex physicochemical environment of the staining system, we developed a highly optimized 3D staining imaging pipeline based on CUBIC. Based on our precise characterization of biological tissues as an electrolyte gel, we experimentally evaluated broad 3D staining conditions by using an artificial tissue-mimicking material. The combination of optimized conditions allows a bottom-up design of a superior 3D staining protocol that can uniformly label whole adult mouse brains, an adult marmoset brain hemisphere, an ~1 cm3 tissue block of a postmortem adult human cerebellum, and an entire infant marmoset body with dozens of antibodies and cell-impermeant nuclear stains. The whole-organ 3D images collected by light-sheet microscopy are used for computational analyses and whole-organ comparison analysis between species. This pipeline, named CUBIC-HistoVIsion, thus offers advanced opportunities for organ- and organism-scale histological analysis of multicellular systems

Nationwide multicentre kidney biopsy study of Japanese patients with type 2 diabetes

金沢大学医薬保健研究域医学系Background. The clinical and pathologic manifestations of nephropathy due to type 2 diabetes are diverse, but large-scale pathologic studies with long-termobservations are limited. Methods. Kidney biopsies and clinical data of 600 patients with type 2 diabetes were collected retrospectively from 13 centres across Japan. Thirteen pathologic findings (nine glomerular lesions, two interstitial lesions and two vascular lesions) were clearly defined and scored. Results. During the observation period, there were 304 composite kidney events [dialysis, doubling of creatinine or reduction of estimated glomerular filtration rate (eGFR) by half], 31 instances of chronic kidney disease (CKD) G5D, 76 cardiovascular events and 73 deaths. The mean observation period was 72.4 months. The distribution of CKD heat map categories for the 600 patients was 103 green or yellow, 149 orange and 348 red. Even in the cases in the green and yellow category, diffuse lesions (81.6%), polar vasculosis (42.6%) and subendothelial space widening (35.1%) were commonly detected. Cox proportional hazard analysis revealed that the presence of nodular lesions [hazard ratio (HR) 21.1, 95% confidence interval (CI) 5.3-84.6], exudative lesions (HR 5.1, 95% CI 1.3-20.3) and mesangiolysis (HR 7.6, 95% CI 2.0-28.8) in cases in the green and yellow category were associated with significantly great impact on composite kidney events after adjustment for clinical risk factors. Conclusions. This nationwide study on kidney biopsy of 600 cases with type 2 diabetes revealed that pathologic findings (presence of nodular lesions, exudative lesions and mesangiolysis) were strong predictors of kidney events in low-risk patients. © The Author 2017.Embargo Period 12 month

Improved kinetic model of hydrogen absorption and desorption in titanium with subsurface transport

We improve our previous kinetic model of hydrogen transport in Ti [Y. Hamamoto et al., Nucl. Mater. Energy 23 (2020) 100751]. The model becomes applicable to both the directional processes of absorption and desorption. The limitation in the covered range of hydrogen molar fraction, previously up to 1 mol-H/mol-Ti, is dissolved. The numerical calculations based on the model with a single set of kinetic parameters closely reproduce a series of experimental hydrogen absorption and desorption data for various temperatures, and thus verify the validity of the model