Asymmetric Agglomerative Hierarchical Clustering Algorithms and Their Evaluations

This paper presents asymmetric agglomerative hierarchical clustering algorithms in an extensive view point. First, we develop a new updating formula for these algorithms, proposing a general framework to incorporate many algorithms. Next we propose measures to evaluate the fit of asymmetric clustering results to data. Then we demonstrate numerical examples with real data, using the new updating formula and the indices of fit. Discussing empirical findings, through the demonstrative examples, we show new insights into the asymmetric clustering.     

Targetted correction of a mutant HPRT gene in mouse embryonic stem cells

Two recent developments suggest a route to predetermined alterations in mammalian germlines. These are, first, the characterization of mouse embryonic stem (ES) cells that can still enter the germline after genetic manipulation in culture and second, the demonstration that homologous recombination between a native target chromosomal gene and exogenous DAN can be used in culture to modify specifically the target locus. We here use gene targetting functionally to correct the mutant hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene in the ES cell line which has previously been isolated and used to produce an HPRT-deficient mouse. This modification of a chosen gene in pluripotent ES cells demonstrates the feasibility of this route to manipulating mammalian genomes in predetermined ways.     

Chemical compass model of avian magnetoreception

Approximately 50 species, including birds, mammals, reptiles, amphibians, fish, crustaceans and insects, are known to use the Earth's magnetic field for orientation and navigation. Birds in particular have been intensively studied, but the biophysical mechanisms that underlie the avian magnetic compass are still poorly understood. One proposal, based on magnetically sensitive free radical reactions, is gaining support despite the fact that no chemical reaction in vitro has been shown to respond to magnetic fields as weak as the Earth's ( approximately 50 muT) or to be sensitive to the direction of such a field. Here we use spectroscopic observation of a carotenoid-porphyrin-fullerene model system to demonstrate that the lifetime of a photochemically formed radical pair is changed by application of < or =50 microT magnetic fields, and to measure the anisotropic chemical response that is essential for its operation as a chemical compass sensor. These experiments establish the feasibility of chemical magnetoreception and give insight into the structural and dynamic design features required for optimal detection of the direction of the Earth's magnetic field.     

弹性体材料拌合的离散元模拟及拌合装置的改进

为了现实有效地离散弹性体材料拌合的数值模拟,采用离散元法,开发了离散弹性体材料拌合离散元模拟系统.通过塑料球落下拌合实验对数值模拟系统进行了验证.实验结果与计算结果接近,表明该系统具有可信性.应用数值模拟系统对现有拌合装置的拌合原理进行了分析,阐明了现有拌合装置的问题,开发了一种新型拌合装置,并对其进行了实验验证和数值模拟.结果表明新型拌合装置的拌合能力高.该材料拌合离散元模拟系统与参数确定方法能够合理地模拟离散体的拌合.     

p53-induced inhibition of Hif-1 causes cardiac dysfunction during pressure overload

Cardiac hypertrophy occurs as an adaptive response to increased workload to maintain cardiac function. However, prolonged cardiac hypertrophy causes heart failure, and its mechanisms are largely unknown. Here we show that cardiac angiogenesis is crucially involved in the adaptive mechanism of cardiac hypertrophy and that p53 accumulation is essential for the transition from cardiac hypertrophy to heart failure. Pressure overload initially promoted vascular growth in the heart by hypoxia-inducible factor-1 (Hif-1)-dependent induction of angiogenic factors, and inhibition of angiogenesis prevented the development of cardiac hypertrophy and induced systolic dysfunction. Sustained pressure overload induced an accumulation of p53 that inhibited Hif-1 activity and thereby impaired cardiac angiogenesis and systolic function. Conversely, promoting cardiac angiogenesis by introducing angiogenic factors or by inhibiting p53 accumulation developed hypertrophy further and restored cardiac dysfunction under chronic pressure overload. These results indicate that the anti-angiogenic property of p53 may have a crucial function in the transition from cardiac hypertrophy to heart failure.     

Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations

Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function-related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function-related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10(-8)). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ～110,347 individuals. We identify pleiotropic associations among these loci with kidney function-related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.     

Primary structure and functional expression of the inositol 1,4,5-trisphosphate-binding protein P400

Cloning and expression of functional P400 protein from cerebellar Purkinje neurons shows that this protein is a receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium.     

Restoration of the poor oxygen transport function of ACD-stored blood by pyridoxal 5′-phosphate

Summary Pyridoxal 5-phosphate is easily incorporated into ACD-stored erythrocytes without decrease of ATP, and restores the poor oxygen transport function with a similar effect to 2,3-diphosphoglycerate.