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小鼠Rad1基因剔除引发皮肤肿瘤易感性

生物物理学报 2009年第S1期25卷 452-452页

作者：韩璐胡志上刘宇恒王向远 Kevin M.Hopkins howard b.lieberman 杭海英国家大分子重点实验室生物物理研究所中国科学院系统中心实验室生物物理研究所中国科学院 Department of Genetics & Development and Obstetrics & Gynecology and The Institute for Human Nutritionand Herbert Irving Comprehensive Cancer CenterColumbia University Medical Center1130St.Nicholas AvenueRoom311BNew YorkNY10032 Center for Radiological Research Columbia UniversityCollege of Physicians and Surgeons630W.168th St.New YorkNY10032 Department of Environmental Health Sciences Columbia UniversityMailman School of Public Health60Haven AvenueSuite B1New YorkNY10032

生物时刻都面对着细胞内源自由基和环境污染物及辐射等 DNA 损伤因素。DNA 复制过程中也会产生 DNA 损伤。生物经过长期进化。

关键词： Mrad1 Mrad9 基因打靶肿瘤发生 DNA损伤

Rad9基因的小鼠角质细胞条件基因敲出增加遗传毒性致癌率

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Rad9基因的小鼠角质细胞条件基因敲出增加遗传毒性致癌率

Surfactant protein A (SP-A) binds to phosphatidylserine and competes with annexin V binding on late apoptotic cells

中国科学技术协会第十届年会21分会场环境因素、遗传毒性与肿瘤学术会议

作者：胡志上刘宇恒张春波赵云何伟韩璐杨蕾蕾 Kevin M.Hopkins 杨晓 howard b.lieberman 杭海英中国科学院生物物理研究所生物大分子重点实验室中国科学院生物物理研究所感染与免于中心首都师范大学生命学院军事医学科学院生物技术研究所遗传发育疾病研究室 Center for Radiological Research College of Physicians and Surgeons Columbia UniversityMailman School of Public HealthNew YorkNew York Department of Environmental Health Sciences Columbia UniversityMailman School of Public HealthNew YorkNew York

生物每天都面对着细胞内源白由基和环境辐射等各种各样的DNA损伤因素,它们依靠高度保守的DNA修复机制抵抗内外源物质的损伤效应,维持细胞基因组的稳定性。在真核生物中,有细胞周期监控点。细胞周期监控点参与DNA损伤修复过程。一个生物...

生物每天都面对着细胞内源白由基和环境辐射等各种各样的DNA损伤因素,它们依靠高度保守的DNA修复机制抵抗内外源物质的损伤效应,维持细胞基因组的稳定性。在真核生物中,有细胞周期监控点。细胞周期监控点参与DNA损伤修复过程。一个生物体受到多大的伤害和其细胞如何应对这种伤害很大程度上决定了他是否会患癌症。Rad9是一个进化上从酵母到人都高度保守的基因,在参与DNA修复和细胞周期监控点调控、维持基因组稳定性中起重要作用。但是,Rad9基因在肿瘤发生中的具体作用还不太清晰。因此,我们建立了基因敲除小鼠模型来研究这个问题。由于将小鼠Rad9基因全身剔除会导致其胚胎致死,所以我们构建了特异地只在角质细胞中剔除Rad9基因的小鼠,来研究该基因在肿瘤发生中的作用。在正常饲养的情况下,杂合和敲除型的Rad9条件剔除小鼠与野生小鼠表型无明显差异。但在小鼠背部皮肤上涂抹DNA损伤药物DMbA后,发现Rad9基因敲除的小鼠比对照鼠显著地易诱导发生皮肤肿瘤,同时易产生皮肤衰老。检测DNA损伤响应基因p21,p53和Rad9的同源基因Mrad9b发现敲除小鼠皮肤中的这些基因与野生小鼠相比表达升高。体外分离培养原代角质细胞发现Rad9基因敲除的细胞与野生细胞相比,其自发DNA损伤以及DMbA诱导的DNA双链断裂均明显增加。若在培养过程中加入抗氧化剂EGCG可以减少这种损伤,提示空气中的氧可导致皮肤角质细胞中DNA损伤,而Rad9有抗这种DNA损伤的作用。综合上述数据可知,基因组不稳定性应是本研究中小鼠皮肤肿瘤诱导发生的关键原因,而Rad9基因在维持角质细胞基因组稳定性和防止皮肤肿瘤发生方面有重要作用。我们利用组织特异性剔除Rad9基因的小鼠第一次从体内水平证明了Rad9是抑癌基因。由此我们有理由关注人体内的Mrad9同源基因是否起到抑癌作用,是否有癌症患者体内存在Rad9突变。我们的工作将有益于对人类肿瘤发生机制的深入探索和发展新的临床检测及治疗方法。

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Protein & Cell 2010年第2期1卷 188-197页

作者： Anne Jäkel Kenneth b.M.Reid howard Clark Department of Pharmacology University of OxfordMansfield RoadOxford OX13QTUK MRC Immunochemistry Unit Department of BiochemistryUniversity of OxfordSouth Parks RoadOxford OX13QUUK University of Southampton MP 803 Level FSouth BlockSouthampton General HospitalSouthampton SO166YDUK

The role of surfactant protein A(SP-A)in the recognition and clearance of apoptotic cells is well established,but to date,it is still not clear which surface molecules of apoptotic cells are involved in the *** we present evidence that phosphatidylserine(PS)is a relevant binding molecule for human *** binding is Ca^(2+)-dependent and is not inhibited by mannose,suggesting that the sugar-binding site of the carbohydrate recognition domain(CRD)of SP-A is not *** cytometry studies on apoptotic Jurkat cells revealed apparent inhibition of annexin V binding by increasing concentrations of SP-A in late apoptotic but not early apoptotic cells,and this was consistent for Jurkat cells and *** these data,confocal microscopy results show a co-localisation of annexin V and SP-A in late apoptotic but not early apoptotic ***,we cannot conclude that this inhibition is exclusively due to the binding of SP-A to PS on the cell surface,as annexin V is not wholly specific for PS and SP-A also interacts with other phospholipids that might become exposed on the apoptotic cell surface.

关键词： surfactant proteins phosphatidylserine apoptotic cells

Surface-bound myeloperoxidase is a ligand for recognition of late apoptotic neutrophils by human lung surfactant proteins A and D

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Protein & Cell 2010年第6期1卷 563-572页

作者： Anne Jäkel howard Clark Kenneth b.M.Reid Robert b.Sim Department of Pharmacology University of OxfordMansfield RoadOxford OX13QTUK University of Southampton School of MedicineDivision of Infection Inflammation&ImmunitySouthampton General HospitalSouthampton SO166YDUK MRC Immunochemistry Unit Department of BiochemistryUniversity of OxfordSouth Parks RoadOxford OX13QUUK

Surfactant proteins A(SP-A)and D(SP-D),both members of the collectin family,play a well established role in apoptotic cell recognition and *** in vitro data show that SP-A and SP-D interact with apoptotic neutrophils in a distinct ***-A and SP-D bind in a Ca^(2+)-dependent manner to viable and early apoptotic neutrophils whereas the much greater interaction with late apoptotic neutrophils is Ca^(2+)-*** surface molecules on the apoptotic target cells responsible for these interactions had not been identified and this study was done to find candidate target ***(MPO),a specific intracellular defense molecule of neutrophils that becomes exposed on the outside of the cell upon apoptosis,was identified by affinity purification,mass-spectrometry and western blotting as a novel binding molecule for SP-A and *** confirm its role in recognition,it was shown that purified immobilised MPO binds SP-A and SP-D,and that MPO is surface-exposed on late apoptotic ***-A and SP-D inhibit binding of an anti-MPO monoclonal Ab to late apoptotic *** microscopy confirmed that anti-MPO mAb and SP-A/SP-D colocalise on late apoptotic *** was identified as a further potential ligand for SP-A,and neutrophil defensin as a target for both proteins.

关键词： SP-A SP-D myeloperoxidase neutrophils flow cytometry mass spectrometry

Optimization of Artificial Viscosity in Production Codes based on Gaussian Regression Surrogate Models

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Communications on Applied Mathematics and Computation 2024年第3期6卷 1521-1550页

作者： Vitaliy Gyrya Evan lieberman Mark Kenamond Mikhail Shashkov Applied Mathematics and Plasma Physics Theoretical DivisionMail Stop B284Los Alamos National LaboratoryLos AlamosNM 87545USA Continuum Models and Numerical Methods Group X-Computational Physics DivisionMail Stop F644Los Alamos National LaboratoryLos AlamosNM 87545USA Lagrangian Codes Group X-Computational Physics DivisionMail Stop T086Los Alamos National LaboratoryLos AlamosNM 87545USA

To accurately model flows with shock waves using staggered-grid Lagrangian hydrodynamics, the artificial viscosity has to be introduced to convert kinetic energy into internal energy, thereby increasing the entropy across shocks. Determining the appropriate strength of the artificial viscosity is an art and strongly depends on the particular problem and experience of the researcher. The objective of this study is to pose the problem of finding the appropriate strength of the artificial viscosity as an optimization problem and solve this problem using machine learning (ML) tools, specifically using surrogate models based on Gaussian Process regression (GPR) and bayesian analysis. We describe the optimization method and discuss various practical details of its implementation. The shock-containing problems for which we apply this method all have been implemented in the LANL code FLAG (burton in Connectivity structures and differencing techniques for staggered-grid free-Lagrange hydrodynamics, Tech. Rep. UCRL-JC-110555, Lawrence Livermore National Laboratory, Livermore, CA, 1992, 1992, in Consistent finite-volume discretization of hydrodynamic conservation laws for unstructured grids, Tech. Rep. CRL-JC-118788, Lawrence Livermore National Laboratory, Livermore, CA, 1992, 1994, Multidimensional discretization of conservation laws for unstructured polyhedral grids, Tech. Rep. UCRL-JC-118306, Lawrence Livermore National Laboratory, Livermore, CA, 1992, 1994, in FLAG, a multi-dimensional, multiple mesh, adaptive free-Lagrange, hydrodynamics code. In: NECDC, 1992). First, we apply ML to find optimal values to isolated shock problems of different strengths. Second, we apply ML to optimize the viscosity for a one-dimensional (1D) propagating detonation problem based on Zel’dovich-von Neumann-Doring (ZND) (Fickett and Davis in Detonation: theory and experiment. Dover books on physics. Dover Publications, Mineola, 2000) detonation theory using a reactive burn model. We compare re

关键词： Optimization Artificial viscosity Gaussian regression surrigate model

Hypoestoxide inhibits tumor growth in the mouse CT26 colon tumor model

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World Journal of Gastroenterology 2007年第34期13卷 4586-4588页

作者： Emmanuel A Ojo-Amaize howard b Cottam Olusola A Oyemade Joseph I Okogun Emeka J Nchekwube Immune Modulation Inc. 2273B South Cactus Avenue Bloomington California 92316 United States

AIM: To evaluate the effect of the natural diterpenoid, hypoestoxide (HE) on the growth of established colon cancer in mice. METHODS: The *** mouse colon carcinoma cell line was grown and expanded in vitro. Following the expansion, bALb/c mice were inoculated s.c. with viable tumor cells. After the tumors had established and developed to about 80-90 mm3, the mice were started on chemotherapy by oral administration of HE, 5-fluorouracil (5-FU) or combination. RESULTS: The antiangiogenic HE has previously been shown to inhibit the growth of melanoma in the b16F1 tumor model in C57bL/6 mice. Our results demonstrate that mean volume of tumors in mice treated with oral HE as a single agent or in combination with 5-FU, were significantly smaller (> 60%) than those in vehicle control mice (471.2 mm3 vs 1542.8 mm3, P burden resulted in pronounced mean survival times (MST) and increased life spans (ILS) in the treated mice. CONCLUSION: These results indicate that HE is an effective chemotherapeutic agent for colorectal cancer in mice and that HE may be used alone or in combination with 5-FU.

关键词： Hypoestoxide 5-Fluorouracil Colon, Cancer Mice

Parallel DNA Constrained by“CC^+Clamps”

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Chemical Research in Chinese Universities 1999年第2期15卷 42-47页

作者： LIU Ke-liang H.Todd Miles Frank b.howard Joe Frazier V.Sasisekharan Laboratory of Molecular biology NIDDKNational Institutes of HealthBethesdaMaryland20892USA

Parallel DNA helices with reverse WatsonCrick pairing have been described in several *** has been pointed out,however,that the parallel structures may also be in equilibrium with antiparallel WatsonCrick helices due to their closely similar *** avoid the problem we have prepared and characterized DNA helices which are constrained to possess parallel polarity by two dC residues,or CC+clamps,at both the ends of AT oligomer *** residues are hemiprotonated below neutral pH,forming two stable CC+base pairs with three hydrogen bonds at each end of the *** physical properties of these constructs can then be used to calibrate those of duplexes having the same sequences but lacking the terminal C *** recent studies indicate that dC acid selfstructures are fourstranded with intercalated bases,gel electrophoresis indicates that these structures are not present in the molecules described here.

关键词： Parallel DNA helices Reverse Watson-Crick pairing CC+ base pair Oligonucleotide helices, Reverse WatsonCrick pairing, CC+ base pair, Oligonucleotide

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山东寒武系馒头组等刺虫化石的发现

古生物学报 2010年第3期49卷 398-406页

作者：王雨楠黄迪颖 lieberman b S 现代古生物学与地层学国家重点实验室中国科学院南京地质古生物研究所南京210008 Department of Geology 1475 Jayhawk Boulevard University of Kansas 120 Lindley Hall Lawrence 66045-7613

等刺虫(Isoxys)是寒武纪海洋中一类分布广泛的双瓣壳节肢动物,在北美、欧洲、澳大利亚、西伯利亚及中国均有发现,但延续时间并不长,目前已经描述了16个已命名的种以及一些未定种化石。等刺虫在我国扬子地台云南滇东地区、贵州凯里、湖... 详细信息

等刺虫(Isoxys)是寒武纪海洋中一类分布广泛的双瓣壳节肢动物,在北美、欧洲、澳大利亚、西伯利亚及中国均有发现,但延续时间并不长,目前已经描述了16个已命名的种以及一些未定种化石。等刺虫在我国扬子地台云南滇东地区、贵州凯里、湖北长阳等地寒武系第二、第三统均有发现。文中报道的等刺虫发现于山东省临沂市刘庄镇馒头组顶部,没有保存软体部分,被命名为一个新种Isoxys shandongensis Wang and Huang ***.。同时,对美国寒武系Spence页岩保存的未定名等刺虫软体部分特征进行修订,并进行形态比较。等刺虫的新发现对探讨这类常见的寒武纪节肢动物的演化、分布和多样性均有一定意义。

关键词：等刺虫馒头组寒武系山东

Review of relaxation oscillations in plasma processing discharges

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Chinese Physics b 2007年第3期16卷 758-765页

作者：周筑文 M. A. lieberman Sungjin Kimb Department of Physics Guizhou Educational College Guiyang 550003 China Department of Electrical Engineering and Computer Sciences- 1770 University of California Berkeley CA 94720 U.S.A

Relaxation oscillations due to plasma instabilities at frequencies ranging from a few Hz to tens of kHz have been observed in various types of plasma processing discharges. Relaxation oscillations have been observed in electropositive capacitive discharges between a powered anode and a metallic chamber whose periphery is grounded through a slot with dielectric spacers. The oscillations of time-varying optical emission from the main discharge chamber show, for example, a high-frequency （- 40 kHz） relaxation oscillation at 13.33Pa, with an absorbed power being nearly the peripheral breakdown power, and a low-frequency （- 3 Hz） oscillation, with an even higher absorbed power. The high-frequency oscillation is found to ignite plasma in the slot, but usually not in the peripheral chamber. The kilohertz oscillations are modelled using an electromagnetic model of the slot impedance, coupled to a circuit analysis of the system including the matching network. The model results are in general agreement with the experimental observations, and indicate a variety of behaviours dependent on the matching conditions. In low-pressure inductive discharges, oscillations appear in the transition between low-density capacitively driven and high-density inductively driven discharges when attaching gases such as SF6 and Ar/SF6 mixtures are used. Oscillations of charged particles, plasma potential, and light, at frequencies ranging from a few Hz to tens of kHz, are seen for gas pressures between 0.133 Pa and 13.33 Pa and discharge powers in a range of 75 1200 W. The region of instability increases as the plasma becomes more electronegative, and the frequency of plasma oscillation increases as the power, pressure, and gas flow rate increase. A volume-averaged （global） model of the kilohertz instability has been developed; the results obtained from the model agree well with the experimental observations.

关键词： relaxation oscillation capacitive discharges inductive discharges plasma instability