An automated multiscale ensemble simulation approach for vascular blood flow

Cerebrovascular diseases such as brain aneurysms are a primary cause of adult disability. The flow dynamics in brain arteries, both during periods of rest and increased activity, are known to be a major factor in the risk of aneurysm formation and rupture. The precise relation is however still an open field of investigation. We present an automated ensemble simulation method for modelling cerebrovascular blood flow under a range of flow regimes. By automatically constructing and performing an ensemble of multiscale simulations, where we unidirectionally couple a 1D solver with a 3D lattice-Boltzmann code, we are able to model the blood flow in a patient artery over a range of flow regimes. We apply the method to a model of a middle cerebral artery, and find that this approach helps us to fine-tune our modelling techniques, and opens up new ways to investigate cerebrovascular flow properties.This work has received funding from the CRESTA project within the EC-FP7 (ICT-2011.9.13) under Grant Agreements no. 287703, and from EPSRC Grants EP/I017909/1 (www.2020science.net) and EP/I034602/1

カルシウム依存的な鞭毛運動の制御に関わるタンパク質カラクシンの構造解析

学位の種別: 課程博士審査委員会委員 : （主査）東京大学准教授 永田 宏次, 東京大学教授 伏信 進矢, 東京大学准教授 葛山 智久, 東京大学准教授 鈴木 道生, 東京大学特任准教授 村瀬 浩司University of Tokyo(東京大学

Morphological descriptions of laboratory reared larvae and post-larvae of the Australian shovel-nosed lobster Thenus australiensis Burton & Davie, 2007 (Decapoda, Scyllaridae)

Complete larval development from newly hatched larvae up to the juvenile stage was successfully achieved in the Australian shovel-nosed lobster Thenus australiensis under laboratory conditions. The larvae of this species passed through four phyllosoma stages (each stage has a single instar), and developed into the first juvenile stage via a post-larval, nisto stage. The shortest and mean durations from hatching to metamorphosis at a water temperature of 25°C were 32 and 38 days, respectively. Morphologies of body and appendages for all four phyllosoma stages and the nisto stage were described. The phyllosomas were fed exclusively on the jellyfish Aurelia aurita throughout their culture. Our results indicate that jellyfish may be a viable diet for T. australiensis phyllosoma's in culture and may therefore be useful for commercial-scale lobster production

Crystal structure of a Ca2+-dependent regulator of flagellar motility reveals the open-closed structural transition

Sperm chemotaxis toward a chemoattractant is very important for the success of fertilization. Calaxin, a member of the neuronal calcium sensor protein family, directly acts on outer-arm dynein and regulates specific flagellar movement during sperm chemotaxis of ascidian, Ciona intestinalis. Here, we present the crystal structures of calaxin both in the open and closed states upon Ca2+ and Mg2+ binding. The crystal structures revealed that three of the four EF-hands of a calaxin molecule bound Ca2+ ions and that EF2 and EF3 played a critical role in the conformational transition between the open and closed states. The rotation of α7 and α8 helices induces a significant conformational change of a part of the α10 helix into the loop. The structural differences between the Ca2+- and Mg2+-bound forms indicates that EF3 in the closed state has a lower affinity for Mg2+, suggesting that calaxin tends to adopt the open state in Mg2+-bound form. SAXS data supports that Ca2+-binding causes the structural transition toward the closed state. The changes in the structural transition of the C-terminal domain may be required to bind outer-arm dynein. These results provide a novel mechanism for recognizing a target protein using a calcium sensor protein

Identifying Japanese students’ core spatial reasoning skills by solving 3D geometry problems: An exploration

This is the final version. Available on open access from SAGE Publications via the DOI in this recordTaking the importance of spatial reasoning skills, this article aims to identify “core” spatial reasoning skills which are likely to contribute to successful problem-solving in three-dimensional (3D) geometry. “Core” spatial skills are those which might be particularly related to students’ successful problem-solving in 3D geometry. In this article, spatial reasoning skills are malleable and can be improved with teaching/interventions with mental rotation, spatial orientation, spatial visualization, and property-based reasoning. To achieve the study aim, we conducted a survey in total of 2,303 Japanese Grade 4–9 students (10–15 years old). We take the following stages of the procedures in this article: (a) Descriptive statistics; (b) 2 parameter logistic model (2PLM) analysis; and (c) Experiments with the Pearson correlation coefficient. As a result, we identified that a set of a few tasks can be used to check if students have “core” spatial skills in 3D geometry. For both primary and secondary, rotating given representations mentally, and imagining and drawing 3D shapes, are important, and for secondary schools, property-based reasoning is also crucial for further problem-solving skills. Our findings and methodological approach have implications for mathematics education research and practice as our results provide clear, and promising principles for task/units/curriculum design for spatial reasoning in which more robust teaching intervention is necessary

Iron bioavailability in two commercial cultivars of wheat: a comparison between wholegrain and white flour and the effects of nicotianamine and 2'-deoxymugineic acid on iron uptake into Caco-2 cells

Iron bioavailability in unleavened white and wholegrain bread made from two commercial wheat varieties was assessed by measuring ferritin production in Caco-2 cells. The breads were subjected to simulated gastrointestinal digestion and the digests applied to the Caco-2 cells. Although Riband grain contained a lower iron concentration than Rialto, iron bioavailability was higher. No iron was taken up by the cells from white bread made from Rialto flour or from wholegrain bread from either variety, but Riband white bread produced a small ferritin response. The results probably relate to differences in phytate content of the breads, although iron in soluble monoferric phytate was demonstrated to be bioavailable in the cell model. Nicotianamine, an iron chelator in plants involved in iron transport, was a more potent enhancer of iron uptake into Caco-2 cells than ascorbic acid or 2'-deoxymugineic acid, another metal chelator present in plants

WNT signalling in prostate cancer

Genome sequencing and gene expression analyses of prostate tumours have highlighted the potential importance of genetic and epigenetic changes observed in WNT signalling pathway components in prostate tumours-particularly in the development of castration-resistant prostate cancer. WNT signalling is also important in the prostate tumour microenvironment, in which WNT proteins secreted by the tumour stroma promote resistance to therapy, and in prostate cancer stem or progenitor cells, in which WNT-β-catenin signals promote self-renewal or expansion. Preclinical studies have demonstrated the potential of inhibitors that target WNT receptor complexes at the cell membrane or that block the interaction of β-catenin with lymphoid enhancer-binding factor 1 and the androgen receptor, in preventing prostate cancer progression. Some WNT signalling inhibitors are in phase I trials, but they have yet to be tested in patients with prostate cancer

The effect of aneurysm geometry on the intra-aneurysmal flow condition

Various anatomical parameters affect on intra-aneurysmal hemodynamics. Nevertheless, how the shapes of real patient aneurysms affect on their intra-aneurysmal hemodynamics remains unanswered. Quantitative computational fluid dynamics simulation was conducted using eight patients’ angiograms of internal carotid artery–ophthalmic artery aneurysms. The mean size of the intracranial aneurysms was 11.5 mm (range 5.8 to 19.9 mm). Intra-aneurysmal blood flow velocity and wall shear stress (WSS) were collected from three measurement planes in each aneurysm dome. The correlation coefficients (r) were obtained between hemodynamic values (flow velocity and WSS) and the following anatomical parameters: averaged dimension of aneurysm dome, the largest aneurysm dome dimension, aspect ratio, and dome–neck ratio. Negative linear correlations were observed between the averaged dimension of aneurysm dome and intra-aneurysmal flow velocity (r = −0.735) and also WSS (r = −0.736). The largest dome diameter showed a negative correlation with intra-aneurysmal flow velocity (r = −0.731) and WSS (r = −0.496). The aspect ratio demonstrated a weak negative correlation with the intra-aneurysmal flow velocity (r = −0.381) and WSS (r = −0.501). A clear negative correlation was seen between the intra-aneurysmal flow velocity and the dome–neck ratio (r = −0.708). A weak negative correlation is observed between the intra-aneurysmal WSS and the dome–neck ratio (r = −0.392). The aneurysm dome size showed a negative linear correlation with intra-aneurysmal flow velocity and WSS. Wide-necked aneurysm geometry was associated with faster intra-aneurysmal flow velocity