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An atlas-based fuzzy connectedness method for automatic tissue classification in brain MRI

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Progress in Natural science:Materials International 2006年第10期16卷 1106-1110页

作者： ZHOU Yongxin and BAI Jing (department of Biomedical Engineering, tsinghua university, beijing 100084, china) department of Biomedical Engineering Tsinghua University Beijing 100084 China

A framework incorporating a subject-registered atlas into the fuzzy connectedness (FC) method is proposed for the automatic tissue classification of 3D images of brain MRI. The pre-labeled atlas is first registered onto the subject to provide an initial approximate segmentation. The initial segmentation is used to estimate the intensity histograms of gray matter and white matter. Based on the estimated intensity histograms, multiple seed voxels are assigned to each tissue automatically. The normalized intensity histograms are utilized in the FC method as the intensity probability density function (PDF) directly. Relative fuzzy connectedness technique is adopted in the final classification of gray matter and white matter. Experimental results based on the 20 data sets from IBSR are included, as well as comparisons of the performance of our method with that of other published methods. This method is fully automatic and operator-independent. Therefore, it is expected to find wide applications, such as 3D visualization, radiation therapy planning, and medical database construction.

关键词： fuzzy connectedness atlas-based segmentation brain tissue classification MR1.

A quantification model for apoptosis in mouse embryos in the early stage of fetation

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science china(life sciences) 2009年第10期52卷 922-927页

作者： WANG PengFei1, FU JianHua1, MA WanYun1, CHEN DieYan1, Lü DanYu2 & BAI WenJia3 1 Key Laboratory for Atomic and Molecular Nanosciences of Education Ministry, department of Physics, tsinghua university, beijing 100084, china 2 department of Anatomy & Histology and Embryology, School of Basic medical sciences Peking university Health science Center, beijing 100083, china 3 department of Automation, tsinghua university, beijing 100084, china Key Laboratory for Atomic and Molecular Nanosciences of Education Ministry Department of Physics Tsinghua University Beijing China department of Anatomy & Histology and Embryology School of Basic Medical Sciences Peking University Health Science Center Beijing China department of Automation Tsinghua University Beijing China

Apoptosis is the most important inducement and modulator for embryos in the early stage of fetation, i.e. after the 8-cell stage, mostly the morula and blastula stage, to proceed to the stage of nonlinear development. Using a two-photon laser scanning microscopy (TPLSM) system, we obtained 3-dimensional (3D) fluorescent images of preimplantation mouse embryos. A model for quantification was established. The statistical results for the spatial location of apoptosis bodies in embryos was obtained following image processing, as well as investigation of the kinetics of apoptosis. It was found that most (70%) apoptosis occurred in the trophectoderm, and the departure between the centroid and geometric center of embryos had a step transition when embryos developed into the 32-cell stage, which was consistent with the theoretical prediction that the blastocele would induce a symmetry break of the distribution of cells in embryos.

关键词： apoptosis preimplantation mouse embryo TPLSM quantification model

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A normalized thoracic coordinate system for atlas mapping in 3D CT images

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Progress in Natural science:Materials International 2008年第1期18卷 111-117页

作者： Hongkai Wang,Jing Bai*,Yonghong Zhang department of Biomedical Engineering,tsinghua university,beijing 100084,china department of Biomedical Engineering Tsinghua University Beijing 100084 China

In this paper,a normalized thoracic coordinate system(NTCS)is defined for rapidly mapping the 4D thoracic organ atlas into indi- vidual CT volume *** coordinate system is defined based on the thoracic *** coordinate values are normalized by the size of the individual thorax so that this coordinate system is universal to different *** compensating the respiratory motion of the organs,a 4D dynamic torso atlas is introduced.A method for mapping this dynamic atlas into the individual image using the NTCS is also *** this method,the dynamic atlas was mapped into the clinical thoracic CT images and rough positions of the organs were found *** NTCS-based 4D atlas mapping method may provide a novel way for estimating the thoracic organ positions in low-resolution molecular imaging modalities,as well as in modern 4D medical images.

关键词： Atlas mapping Registration Segmentation Molecular imaging

Role of inositol 1,4,5-trisphosphate receptors in α1-adrenergic receptorinduced cardiomyocyte hypertrophy

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Acta Pharmacologica Sinica 2006年第7期27卷 895-900页

作者： Da-li LUO~(2,3,5) Jian GAO~2 Xiao-mei LAN~3 Gang WANG~4 Sheng WEI~4 Rui-ping XIAO~4 Qi-de HAN~32 department of Pharmacology,School of Chemical Biology & Pharmaceutical sciences,Capital university of medical sciences,beijing 100069,china 3 institute of Cardiovascular science at Health science Center,Peking university beijing 100083,china 4 institute of Molecular Medicine and College of life science,Peking university,beijing 100871,china department of Pharmacology School of Chemical Biology & Pharmaceutical Sciences Capital University of Medical Sciences Beijing China institute of Cardiovascular science at Health science Center Peking University Beijing China institute of Molecular Medicine and College of life science Peking University Beijing China

Aim:Intracellular Ca2+plays pivotal roles in diverse cellular functions,includinggene transcription that underlies cardiac remodeling during stress ***,the role of inositol 1,4,5-trisphosphate receptors（IP3Rs）in the media-tion of cardiac intracellular Ca2+and hypertrophic growth remains *** with neonatal rat ventricular myocytes suggests that activation of IP3Rsmay be linked to α1adrenergic receptor（α1AR）increased stereotyped Ca2+sparkoccurrence and global Ca2+***,we hypothesized that Ca2+releasethrough IP3Rs was necessary for α1AR-stimulated cardiac ***:We used myoinositol 1,4,5-trisphosphate hexakis（butyryloxymethyl）ester（IP3BM）,a membrane-permeant ester of IP3,to activate IP3Rs directly,and Fluo 4/AM tomeasure intracellular Ca2+***:IP3BM(10μmol·L-1)mimicked theeffects of phenylephrine,a selective agonist of α1AR,in increments in local Ca2+spark release（especially in the perinuclear area）and global Ca2+*** importantly,IP3R inhibitors,2-aminoethoxydiphenyl borateand Xestospongin C,abolished the IP3BM-induced Ca2+responses,and signifi-cantly suppressed α1AR-induced cardiomyocyte hypertrophy assayed by cellsize,[3H]leucine incorporation and atrial natriuretic factor gene expression,dur-ing sustained（48 h）phenylephrine ***:These results,therefore,provide cellular mechanisms that link IP3R signaling to α1AR-stimulatedgene expression and cardiomyocyte hypertrophy.

关键词： inositol 1,4,5-trisphosphate receptors Ca2+sparks α1 adrenergic stimulation cardiac hypertrophy

Right prefrontal laterality of Chinese boys during a Chinese high conflict Stroop task measured by multi-channel near-infrared spectroscopy imaging

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Progress in Natural science:Materials International 2007年第9期17卷 1023-1028页

作者： Liu Jiacheng1,Bai Jing1,Peng Miao2,Fan Xiaofei1 and Guo Qiyong3(1.department of Biomedical Engineering,tsinghua university,beijing 100084,china 2.department of Electroneurophysiology,the Sixth Hospital of Peking university,beijing 100085,china 3.department of Radiology,The Second Hospital of china medical university,Shenyang 110003,china) department of Biomedical Engineering Tsinghua University Beijing 100084 China department of Electroneurophysiology Sixth Hospital of Peking University Beijing 100085 China department of Radiology Second Hospital of China Medical University Shenyang 110003 China

Some studies have shown that native Chinese speakers have different laterality in matched Stroop tasks from native English ***,many imaging data,which show left laterality of English-matched Stroop interference,have been *** a few functional imaging studies have been conducted to investigate the phenomenon of the Chinese version of Stroop *** this study,functional activity in the lateral prefrontal cortex of a group of normal Chinese boys with functional near-infrared imaging during a Stroop color-word task was measured to show different Stroop interferences in the prefrontal *** results show obvious fluctuation of the cerebral blood volume in the right prefrontal cortex in all boys,which agrees with the finding of previous studies,that is,Chinese native boys have right laterality in their brain when the Chinese version of Stroop color-word task is applied.

关键词： laterality Stroop effect prefrontal cortex near-infrared

Detecting robust gene signature through integrated analysis of multiple types of high-throughput data in liver cancer

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Acta Pharmacologica Sinica 2007年第12期28卷 2005-2010页

作者： Xin-yu ZHANG~(2,3,4,6),Tian-tian LI~(5,6),Xiang-jun LIU~(2,3,4,7)~2 department of Biological science and Biotechnology,~3 School of Biomedicine and ~4 Ministry of Education Key Laboratory of Bioinformatics,tsinghua university beijing 100084,china ~5 Laboratory of medical Genetics,department of Biology,Harbin medical university,Harbin150086.china department of Biological science and Biotechnology Tsinghua University Beijing China School of Biomedicine Tsinghua University Beijing China Ministry of Education Key Laboratory of Bioinformatics Tsinghua University Beijing China department of Biology Laboratory of Medical Genetics Harbin Medical University Harbin China

Aim:To investigate the robust gene signature in liver cancer,we applied anintegrated approach to perform a joint analysis of a highly diverse collection ofliver cancer genome-wide datasets,including genomic alterations and transcrip-tion ***:1-class Significance Analysis of Microarrays coupled withranking score method were used to identify the robust gene signature in livertumor ***:In total,1 625 051 gene expression measurements from 16public microarrays,2 pairs of serial analyses of gene expression experiments,and252 loss of heterozygosity reports obtained from 568 publications were used inthis integrated *** resulting robust gene signatures included 90 genes,which may be of great importance to liver cancer research.A system assessmentanalysis revealed that our integrative method had an accuracy of 92% and acorrelation coefficient value of ***:The system assessment resultsindicated that our method had the ability of integrating the datasets from varioustypes of sources,and eliciting more accurate results,as can be very useful in thestudy of liver cancer.

关键词： liver cancer integrated analysis robust gene signature gene expression map microarray SAGE

Effects of disinhibition on spatiotemporal pattern of neuronal first recruitment in neuronal networks

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Progress in Natural science:Materials International 2009年第5期19卷 615-621页

作者： Liangbin Pana,b,c,1, Xindong Songa,b,c,1, Guangxin Xiang a,b,c, Jing Zhua,b,c, Jing Cheng a,b,c,d,a medical Systems Biology Research Center, tsinghua university School of Medicine, beijing 100084, china b department of Biological sciences and Biotechnology, tsinghua university, beijing 100084, china c National Engineering Research Center for beijing Biochip Technology, 18 life science Parkway, beijing 102206, china d State Key Laboratory of Biomembrane and Membrane Biotechnology, tsinghua university, beijing 100084, china medical Systems Biology Research Center Tsinghua University School of Medicine Beijing 100084 China department of Biological sciences and Biotechnology Tsinghua University Beijing 100084 China National Engineering Research Center for beijing Biochip Technology 18 Life Science Parkway Beijing 102206 China State Key Laboratory of Biomembrane and Membrane Biotechnology Tsinghua University Beijing 100084 China

The propagation of neuronal activities is a key feature to understanding information processing in networks. The analysis based on first-spikes of bursts in turn plays an important role in the research of neuronal activity propagation. Our focus here is to investigate how spatiotemporal patterns of neuronal first-spikes are affected by disinhibition. Multi-electrode arrays were used to record stimulation-evoked bursts of multiple neurons in randomly cultured neuronal networks. Both the precise timing of and the rank relationships between first-spikes were analyzed. Compared with evoked bursts in the network’s native state, the precise first-spike latencies in its dis-inhibited state are more consistent and the propagation of its bursting activities is much faster. Additional points of interest are that disinhibited neuronal networks can be evoked to generate stable and distinguishable neuronal first recruitment spatiotemporal patterns specific to the stimulation site, and that the disinhibition may cause the original spatiotemporal patterns to change in a heterogeneous manner with regards to different propagation pathways.

关键词： Neuronal recruitment Spatiotemporal pattern Disinhibition Network Multi-electrode array

Establishment of liver specific glucokinase gene knockout mice: a new animal model for screening anti-diabetic drugs

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Acta Pharmacologica Sinica 2004年第12期25卷 93-99页

作者： Ya-li ZHANG, Xiao-hong TAN2, Mei-fang XIAO, Hui LI, Yi-qing Mao, Xiao YANG2, Huan-ran TAN3 department of Pharmacology, School of Basic medical science, Peking university Health science Center, beijing 100083 2institute of Biotechnology Academy ofMilitary medical science, beijing 100071, china department of Pharmacology School of Basic Medical Science Peking University Health Science Center 北京 100083 institute of Biotechnology Academy of Military medical science 北京 100071

AIM: To characterize the liver-specific role of glucokinase in maintaining glucose homeostasis and to create an animal model for diabetes. METHODS: We performed hepatocyte-specific gene knockout of glucokinase in mice using Cre-loxP gene targeting strategy. First, two directly repeated loxP sequences were inserted to flank the exon 9 and exon 10 of glucokinase in genomic DNA. To achieve this, linearized targeting vector was electroporated into ES cells. Then G418- and Gancyclovir-double-resistant clones were picked and screened by PCR analysis and the positives identified by PCR were confirmed by Southern blot. A targeted clone was selected for microinjection into C57BL/6J blastocysts and implanted into pseudopregnant FVB recipient. Chimeric mice and their offspring were analyzed by Southern blot. Then by intercrossing the Alb-Cre transgenic mice with mice containing a conditional gk allele, we obtained mice with liver-specific glucokinase gene knockout. RESULTS: Among 161 double resistant clones 4 were positive to PCR and Southern blot and only one was used for further experiments. Eventually we generated the liver specific glucokinase knockout mice. These mice showed increased glucose level with age and at the age of 6 weeks fasting blood glucose level was significantly higher than control and they also displayed impaired glucose tolerance. CONCLUSION: Our studies indicate that hepatic glucokinase plays an important role in glucose homeostasis and its deficiencies contribute to the development of diabetes. The liver glucokinase knock- out mouse is an ideal animal model for MODY2, and it also can be applied for screening anti-diabetic drugs.

关键词： animal disease model non insulin dependent diabetes mellitus type 2 diabetes mellitus glucokinase knockout mice

Tissue-specific expression of GFP reporter gene in germline driven by GATA-2 promoter and enhancers in zebrafish

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Chinese science Bulletin 2000年第1期45卷 31-34,97页

作者： MENG Anming & LIN Shuo1. Laboratory of Developmental Biology, department of Biological sciences and Biotechnology, tsinghua university, beijing 100084, china 2. institute of Molecular Medicine and Genetics, medical College of Georgia, Augusta, GA 30912, USA Laboratory of Developmental Biology Department of Biological Sciences and Biotechnology Tsinghua University Beijing China institute of Molecular Medicine and Genetics Medical College of Georgia Augusta USA

GATA-2, a transcription factor, is expressed in several types of blood cells and in the central nervous system (CNS), and regulates the differentiation of these cells. We have obtained five zebrafish transgenic germlines that carry and express the green fluorescent protein (GFP) gene ligated to various 5’ flanking sepuences of zebrafish GATA-2 gene. The spatial pattern of GFP expression varies, mainly depending on which regulatory sequence is used, among the germlines. In some of the germlines, the expression of GFP is restricted to the CNS and the enveloping layer (EVL) cells, while in some other lines GFP is observed only in the CNS. it is noted that the intensity of GFP in the transgenic fish remain unchanged after a six-generation passage of the transgenes. The transgenic fish could find its uses in the future in generating tissue-specific, even cellspecific mutant fish and in functional study of related genes through transgenesis.

关键词： zebrafish transgenic GATA-2 GFP germline.

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