The circular SiZer, inferred persistence of shape parameters and application to early stem cell differentiation

We generalize the SiZer of Chaudhuri and Marron (J. Amer. Statist. Assoc. 94 (1999) 807-823, Ann. Statist. 28 (2000) 408-428) for the detection of shape parameters of densities on the real line to the case of circular data. It turns out that only the wrapped Gaussian kernel gives a symmetric, strongly Lipschitz semi-group satisfying "circular" causality, that is, not introducing possibly artificial modes with increasing levels of smoothing. Some notable differences between Euclidean and circular scale space theory are highlighted. Based on this, we provide an asymptotic theory to make inference about the persistence of shape features. The resulting circular mode persistence diagram is applied to the analysis of early mechanically-induced differentiation in adult human stem cells from their actin-myosin filament structure. As a consequence, the circular SiZer based on the wrapped Gaussian kernel (WiZer) allows the verification at a controlled error level of the observation reported by Zemel et al. (Nat. Phys. 6 (2010) 468-473): Within early stem cell differentiation, polarizations of stem cells exhibit preferred directions in three different micro-environments.Comment: Published at http://dx.doi.org/10.3150/15-BEJ722 in the Bernoulli (http://isi.cbs.nl/bernoulli/) by the International Statistical Institute/Bernoulli Society (http://isi.cbs.nl/BS/bshome.htm

星湖心学形成の研究 : 堅守と自得の折衷そして西学

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 川原 秀城, 東京大学教授 早乙女 雅博, 東京大学准教授 六反田 豊, 埼玉大学教授 権 純哲, 京都府立大学教授 中 純夫University of Tokyo(東京大学

Analysis of Long-Range Transport of Carbon Dioxide and Its High Concentration Events over East Asian Region Using GOSAT Data and GEOS-Chem Modeling

This study aims to evaluate the long-range transport of CO2 in East Asian region, using concentration data in a surface measurement site (Gosan Station), column averaged concentration data of satellite-borne instrument (GOSAT), and GEOS-Chem modeling results for the period of June 2009 to May 2011. We perform a validation of the data from GOSAT and GEOS-Chem with total column observations (TCCON). The analysis of the long-range transport and high concentration (HC) events using surface/satellite observations and modeling results is conducted. During the HC events, the concentrations in CO2 and other air pollutants such as SO2 and CO are higher than that of all episodes. It means that CO2, known as a globally well-mixed gas, may also act as a fingerprint of human activity with unique regional characteristics like other air pollutants. This comprehensive analysis, in particular with GOSAT CO2 observation data, shows that CO2 plume with high concentration can be long-range transported with 1-2 days' duration with regional scale. We can find out with GEOS-Chem tagging simulation that more than 45% of the elevated CO2 concentration over central/eastern China, Korea, and Japan on high concentration days can be explained by emission sources of East Asia mainland.open0

Principal nested shape space analysis of molecular dynamics data

Molecular dynamics simulations produce huge datasets of temporal sequences of molecules. It is of interest to summarize the shape evolution of the molecules in a succinct, low-dimensional representation. However, Euclidean techniques such as principal components analysis (PCA) can be problematic as the data may lie far from in a flat manifold. Principal nested spheres gives a fundamentally different decomposition of data from the usual Euclidean sub-space based PCA (Jung et al., 2012). Sub-spaces of successively lower dimension are fitted to the data in a backwards manner, with the aim of retaining signal and dispensing with noise at each stage. We adapt the methodology to 3D sub-shape spaces and provide some practical fitting algorithms. The methodology is applied to cluster analysis of peptides, where different states of the molecules can be identified. Also, the temporal transitions between cluster states are explored

Smoothing splines on Riemannian manifolds, with applications to 3D shape space

© 2020 The Authors. Journal of the Royal Statistical Society: Series B (Statistical Methodology) published by John Wiley & Sons Ltd on behalf of Royal Statistical Society There has been increasing interest in statistical analysis of data lying in manifolds. This paper generalizes a smoothing spline fitting method to Riemannian manifold data based on the technique of unrolling, unwrapping and wrapping originally proposed by Jupp and Kent for spherical data. In particular, we develop such a fitting procedure for shapes of configurations in general m-dimensional Euclidean space, extending our previous work for two-dimensional shapes. We show that parallel transport along a geodesic on Kendall shape space is linked to the solution of a homogeneous first-order differential equation, some of whose coefficients are implicitly defined functions. This finding enables us to approximate the procedure of unrolling and unwrapping by simultaneously solving such equations numerically, and so to find numerical solutions for smoothing splines fitted to higher dimensional shape data. This fitting method is applied to the analysis of some dynamic 3D peptide data

Prospective Validation of FibroTest in Comparison with Liver Stiffness for Predicting Liver Fibrosis in Asian Subjects with Chronic Hepatitis B

Liver stiffness measurement (LSM) and FibroTest (FT) are frequently used as non-invasive alternatives for fibrosis staging to liver biopsy. However, to date, diagnostic performances of Enhanced Liver Fibrosis (ELF) test, which consists of hyaluronic acid, aminoterminal propeptide of procollagen type-III, and tissue inhibitor of matrix metalloproteinases-1, have not been compared to those of LSM and FT in Asian chronic hepatitis B (CHB) patients.Between June 2010 and November 2011, we prospectively enrolled 170 CHB patients who underwent liver biopsies along with LSM, FT, and ELF. The Batts system was used to assess fibrosis stages.Areas under receiver operating characteristic curves (AUROCs) to predict significant fibrosis (F≥2), advanced fibrosis (F≥3), and cirrhosis (F = 4) were 0.901, 0.860, and 0.862 for ELF, respectively; 0.937, 0.956, and 0.963 for LSM; and 0.896, 0.921, and 0.881 for FT. AUROCs to predict F≥2 were similar between each other, whereas LSM and FT had better AUROCs than ELF for predicting F≥3 (both p<0.05), and LSM predicted F4 more accurately than ELF (p<0.05). Optimized cutoffs of ELF to maximize sum of sensitivity and specificity were 8.5, 9.4, and 10.1 for F≥2, F≥3, and F = 4, respectively. Using suggested ELF, LSM and FT cutoffs to diagnose F1, F2, F3, and F4, 91 (53.5%), 117 (68.8%), and 110 (64.7%) patients, respectively, were correctly classified according to histological results.ELF demonstrated considerable diagnostic value in fibrosis staging in Asian CHB patients, especially in predicting F≥2. However, LSM consistently provided better performance for predicting F≥3 and F4

Functional role of aspartic proteinase cathepsin D in insect metamorphosis

BACKGROUND: Metamorphosis is a complex, highly conserved and strictly regulated development process that involves the programmed cell death of obsolete larval organs. Here we show a novel functional role for the aspartic proteinase cathepsin D during insect metamorphosis. RESULTS: Cathepsin D of the silkworm Bombyx mori (BmCatD) was ecdysone-induced, differentially and spatially expressed in the larval fat body of the final instar and in the larval gut of pupal stage, and its expression led to programmed cell death. Furthermore, BmCatD was highly induced in the fat body of baculovirus-infected B. mori larvae, suggesting that this gene is involved in the induction of metamorphosis of host insects infected with baculovirus. RNA interference (RNAi)-mediated BmCatD knock-down inhibited programmed cell death of the larval fat body, resulting in the arrest of larval-pupal transformation. BmCatD RNAi also inhibited the programmed cell death of larval gut during pupal stage. CONCLUSION: Based on these results, we concluded that BmCatD is critically involved in the programmed cell death of the larval fat body and larval gut in silkworm metamorphosis

The Effect of Environmental Enrichment on Glutathione-Mediated Xenobiotic Metabolism and Antioxidation in Normal Adult Mice

Olfactory bulb (OB) plays an important role in protecting against harmful substances via the secretion of antioxidant and detoxifying enzymes. Environmental enrichment (EE) is a common rehabilitation method and known to have beneficial effects in the central nervous system. However, the effects of EE in the OB still remain unclear. At 6 weeks of age, CD-1® (ICR) mice were assigned to standard cages or EE cages. After 2 months, we performed proteomic analysis. Forty-four up-regulated proteins were identified in EE mice compared to the control mice. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes Pathway demonstrated that the upregulated proteins were mainly involved in metabolic pathways against xenobiotics. Among those upregulated proteins, 9 proteins, which participate in phase I or II of the xenobiotic metabolizing process and are known to be responsible for ROS detoxification, were validated by qRT-PCR. To explore the effect of ROS detoxification mediated by EE, glutathione activity was measured by an ELISA assay. The ratio of reduced glutathione to oxidized glutathione was significantly increased in EE mice. Based on a linear regression analysis, GSTM2 and UGT2A1 were found to be the most influential genes in ROS detoxification. For further analysis of neuroprotection, the level of iNOS and the ratio of Bax to Bcl-2 were significantly decreased in EE mice. While TUNEL+ cells were significantly decreased, Ki67+ cells were significantly increased in EE mice, implicating that EE creates an optimal state for xenobiotic metabolism and antioxidant activity. Taken together, our results suggested that EE protects olfactory layers via the upregulation of glutathione-related antioxidant and xenobiotic metabolizing enzymes, eventually lowering ROS-mediated inflammation and apoptosis and increasing neurogenesis. This study may provide an opportunity for a better understanding of the beneficial effects of EE in the OB