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LQT1 Genotype in Tachypaced Cardiomyopathy Causes Discordance of Baseline and VF Refractoriness

BIOPHYSICAL JOURNAL 2010年第3期98卷 334A-334A页

作者： Ziv, Ohad Lau, Emily Schofield, Lorraine Chaves, Lenny peng, xuwen Choi, Bum-Rak Koren, Gideon Rhode Isl Hosp Providence RI USA Penn State Univ Hershey PA USA

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Dynamics behavior of homogeneous dielectric barrier discharge at atmospheric pressure

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JOURNAL OF APPLIED PHYSICS 2009年第2期106卷 023307-023307-6页

作者： Zhang, Yan Gu, Biao Wang, Wenchun Wang, Dezhen peng, xuwen Dalian Univ Technol State Key Lab Mat Modificat Laser Ion & Elect Bea Dalian 116024 Peoples R China Henan Polytech Univ Sch Mech & Power Engn Henan 454000 Peoples R China Dalian Univ Technol Sch Phys & Optoelect Technol Dalian 116024 Peoples R China

An experimental study on the dynamics behavior of homogeneous dielectric barrier discharge (HDBD) at atmospheric pressure is described in this paper. Two kinds of discharge mode, glow and Townsend discharge modes, can be easily identified according to the differential conductivity of current-voltage relationship in the ascent stage of discharge current for the atmospheric HDBD. A (three-dimensional) 3D phase space made by discharge current, gas gap voltage, and charge density of dielectric-plate surface was utilized in the study. By projecting the discharge evolution trajectory in the 3D space, the 3D trajectory of multiple current peaks discharge in atmospheric helium shows a limited cycle with convolutions and undergoes a series of bifurcation process;however, the 3D trajectory of atmospheric N-2 HDBD is a limited cycle without any convolution and bifurcation process. In addition, the first ionization coefficient of working gas plays a key role to determine the discharge mode of atmospheric HDBD, the transition of discharge mode and the dynamics stability of atmospheric HDBD. (C) 2009 American Institute of Physics. [DOI: 10.1063/1.3159881]

关键词： DIELECTRICS ATMOSPHERIC pressure IONIZATION (Atomic physics) HELIUM CONVOLUTIONS (Mathematics) PHASE space (Statistical physics)

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Experimental investigation on large-area dielectric barrier discharge in atmospheric nitrogen and air assisted by the ultraviolet lamp

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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2009年第3期72卷 460-464页

作者： Zhang, Yan Gua, Biao Wang, Wenchun Wang, Dezhen peng, xuwen Dalian Univ Technol State Key Lab Mat Modificat Laser Ion & Electron Dalian 116024 Peoples R China Dalian Univ Technol Sch Phys & Optoelect Technol Dalian 116024 Peoples R China

In this paper, ultraviolet radiation produced by the ultraviolet lamp is employed to supply pre-ionization for the dielectric barrier discharge in N-2 or air at atmospheric pressure. The effect of the ultraviolet preionization on improving the uniformity of the dielectric barrier discharge is investigated experimentally. The atmospheric pressure glow discharge of the large area (270 mm x 120 mm) is obtained successfully via the ultraviolet pre-ionization in atmospheric DBD in N-2 when the gas gap decrease to 3 mm. Based on the emission spectra, the mechanism which ultraviolet pre-ionization improves the uniformity of the dielectric barrier discharge is discussed. (c) 2008 Elsevier B.V. All rights reserved.

关键词： Pre-ionization Ultraviolet lamp Emission spectra Dielectric barrier discharge Atmospheric pressure

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Origin of complex behaviour of spatially discordant alternans in a transgenic rabbit model of type 2 long QT syndrome

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JOURNAL OF PHYSIOLOGY-LONDON 2009年第19期587卷 4661-4680页

作者： Ziv, Ohad Morales, Eduardo Song, Yoon-kyu peng, xuwen Odening, Katja E. Buxton, Alfred E. Karma, Alain Koren, Gideon Choi, Bum-Rak Brown Univ Warren Alpert Med Sch Rhode Isl Hosp Div CardiolCardiovasc Res Ctr Providence RI 02903 USA Brown Univ Div Engn Providence RI 02903 USA Penn State Univ Coll Med Dept Comparat Med Hershey PA USA Northeastern Univ Dept Phys Boston MA 02115 USA

Enhanced dispersion of repolarization has been proposed as an important mechanism in long QT related arrhythmias. Dispersion can be dynamic and can be augmented with the occurrence of spatially out-of-phase action potential duration (APD) alternans (discordant alternans;DA). We investigated the role of tissue heterogeneity in generating DA using a novel transgenic rabbit model of type 2 long QT syndrome (LQT2). Littermate control (LMC) and LQT2 rabbit hearts (n = 5 for each) were retrogradely perfused and action potentials were mapped from the epicardial surface using di-4-ANEPPS and a high speed CMOS camera. Spatial dispersion (delta APD and delta slope of APD restitution) were both increased in LQT2 compared to LMC (delta APD: 34 +/- 7 ms vs. 23 +/- 6 ms;delta slope:1.14 +/- 0.23 vs. 0.59 +/- 0.19). Onset of DA under a ramp stimulation protocol was seen at longer pacing cycle length (CL) in LQT2 compared to LMC hearts (206 +/- 24 ms vs. 156 +/- 5 ms). Nodal lines between regions with APD alternans out of phase from each other were correlated with conduction velocity (CV) alternation in LMC but not in LQT2 hearts. In LQT2 hearts, larger APD dispersion was associated with onset of DA at longer pacing CL. At shorter CLs, closer to ventricular fibrillation induction (VF), nodal lines in LQT2 (n = 2 out of 5) showed persistent complex beat-to-beat changes in nodal line formation of DA associated with competing contribution from CV restitution and tissue spatial heterogeneity, increasing vulnerability to conduction block. In conclusion, tissue heterogeneity plays a significant role in providing substrate for ventricular arrhythmia in LQT2 rabbits by facilitating DA onset and contributing to unstable nodal lines prone to reentry formation.

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Strong and Specific Protective and Therapeutic Immunity Induced by Single HLA-A2.1 Restricted Epitope DNA Vaccine in Rabbits

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Procedia in Vaccinology 2009年第1期1卷 4-14页

作者： Hu, Jiafen Schell, Todd D. peng, xuwen Cladel, Nancy M. Balogh, Karla K. Christensen, Neil D. Jake Gittlen Cancer Research Foundation Pennsylvania State University College of Medicine Hershey PA 17033 United States Department of Pathology Pennsylvania State University College of Medicine Hershey PA 17033 United States Department of Microbiology and Immunology Pennsylvania State University College of Medicine Hershey PA 17033 United States Department of Comparative Medicine Pennsylvania State University College of Medicine Hershey PA 17033 United States

An HLA-A2.1 transgenic rabbit /Cottontail rabbit papillomavirus (CRPV) infection model has been reported previously. In this study, we incorporated online MHCI epitope prediction software and HLA-A2.1 transgenic mouse and rabbit systems together to demonstrate an efficient way to identify and test immunogenicity of two HLA-A2.1 restricted epitopes from CRPVE1 (161-169 LLFRQAHSV and 303-311 MLQEKPFQL). Both epitopes were able to induce specific cytotoxic CD8 T cells in HLA-A2.1 mice and rabbits after peptide and DNA immunization and in vitro stimulation respectively. Using an epitope DNA vaccination method, we achieved partial and complete protection against CRPV DNA challenge by CRPVE1/161-169 and CRPVE1/303-311 respectively in HLA-A2.1 transgenic outbred rabbits. CRPVE1/303-311 also showed strong and specific therapeutic effects in CRPV-infected HLA-A2.1 transgenic outbred rabbits. Interestingly, epitope CRPVE1/303-311 (but not E1/161-169) showed strong protective immunity in non-transgenic EIII/JC inbred (but not outbred) NZW rabbits. Our data demonstrates an efficient way to identify HLA-A2.1 restricted epitopes for the development of prophylactic and therapeutic vaccines. © 2009.

关键词： A2 CRPV Epitope DNA vaccine Transgenic mouse Transgenic rabbit

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Estradiol and Progesterone Exert Opposite Effects on Cardiac Repolarization and Arrhythmogenesis in Transgenic Long QT Syndrome 2 Rabbits

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BIOPHYSICAL JOURNAL 2009年第3期96卷 563A-563A页

作者： Odening, Katja E. peng, xuwen Choi, Bum-Rak Brunner, Michael Chaves, Leonard Schofield, Lorraine Zehender, Manfred Koren, Gideon Brown Univ Rhode Isl Hosp Warren Alpert Med Sch Cardiovasc Res CtrDiv Cardiol Providence RI 02903 USA Penn State Univ Coll Med Dept Comparat Med Hershey PA USA Univ Freiburg Kardiol Innere Med 3 Freiburg Germany

Introduction: Adult women with LQT2 are at higher risk for sudden cardiac death (SCD) than men with an increased risk during the postpartum. We have created transgenic rabbits over-expressing a pore mutant of the human ERG channel in the heart (LQT2) and showing the human long QT phenotype (Brunner et al. JCI, 2008). 4/4 LQT2 females used for breeding died of SCD during the postpartum. We hypothesize that sex hormones modulate cardiac repolarization and arrhythmogenesis in LQT2 females. Methods: Prepubertal ovariectomized LQT2 females were implanted with 90day release-pellets of estradiol (EST), progesterone (Prog), dihydrotestosterone (DHT), or placebo (OVX) (n=6 each). All groups underwent telemetric ECG monitoring and in vivo electrophysiological studies (EPS) after 8 weeks and first optical mapping experiments were performed in OVX, EST- and DHT-treated rabbits. Results: EST treatment steepened the QT/RR slope of prepubertal rabbits (p<0.05), whereas DHT or OVX decreased the QT/RR slope steepness (p<0.05). Prog did not alter the QT/RR slope. In vivo EPS revealed a longer ventricular refractory period (VERP) in EST- than in DHT- or Prog-treated rabbits (DHT: p<0.05, Prog: p<0.01). Within 8 weeks of hormone-treatment, 4 of 6 EST-treated rabbits died of polymorphic VT, while no SCD occurred in 6 DHT- and 6 Prog-treated LQT2 females (p<0.05). Preliminary optical mapping experiments revealed heterogeneous APD dispersion with islands of prolonged refractoriness in EST- rabbits contrasting with smoother APD dispersion in OVX and DHT-treated rabbits. Conclusions: EST increases the QT/RR steepness and prolongs cardiac refractoriness, whereas DHT and Prog shorten cardiac refractoriness. EST predisposes prepubertal LQT2 rabbits to polymorphic VT. Heterogeneous ADP dispersion might underlie this proarrhythmic effect of EST. We are currently using high-throughput molecular approaches to elucidate the underlying mechanisms.

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Multiple current peaks and mode conversion of atmospheric pressure glow dielectric barrier discharge in helium

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THIN SOLID FILMS 2008年第21期516卷 7547-7554页

作者： Zhang, Yan Gu, Biao peng, xuwen Wang, Dezhen Wang, Wenchun Dalian Univ Technol State Key Lab Mat Modificat Laser Ion & Elect Bea Dalian 116024 Peoples R China Dalian Univ Technol Sch Phys & Optoelect Technol Dalian 116024 Peoples R China

Experimental research was performed on the multiple current peaks (MCP) in atmospheric pressure glow dielectric barrier discharge in helium. In a MCP discharge sequence, the next discharge pulse is always affected by the previous one. The accumulated charges on the dielectric plate play an important role in the MCP formation. In addition, two discharge modes, glow and Townsend discharge modes, can be observed in a MCP discharge sequence. The discharge mode tends to convert from glow to Townsend discharge mode when increasing the applied voltage, decreasing the gas gap and reducing driving frequency, respectively. (C) 2008 Elsevier B.V. All rights reserved.

关键词： glow dielectric barrier discharge multiple current peaks discharge mode atmospheric pressure

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Protective immunity with an E1 multivalent epitope DNA vaccine against cottontail rabbit papillomavirus (CRPV) infection in an HLA-A2.1 transgenic rabbit model

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VACCINE 2008年第6期26卷 809-816页

作者： Hu, Jiafen Cladel, Nancy peng, xuwen Balogh, Karla Christensen, Neil D. Penn State Univ Coll Med Dept Immunol & Microbiol Hershey PA 17033 USA Penn State Univ Coll Med Jake Gittien Canc Res Fdn Hershey PA 17033 USA Penn State Univ Coll Med Dept Pathol Hershey PA 17033 USA Penn State Univ Coll Med Dept Comparat Med Hershey PA 17033 USA

Cottontail rabbit papillomavirus (CRPV)/rabbit model is widely used to study pathogenesis of papillomavirus infections and malignant tumor progression. Recently, we established HLA-A2.1 transgenic rabbit lines and demonstrated efficacy for the testing of immunogenicity of a well-known A2-resticted epitope (HPV16E7/82-90) [Hu J, peng X, Schell TD, Budgeon LR, Cladel NM, Christensen ND. An HLA-A2.1-transgenic rabbit model to study immunity to papillomavirus infection. J Immunol 2006;177(11):8037-45]. In the present study, we screened five HLA-A2.1 restricted epitopes from CRPVE1 (selected using online MHCI epitope prediction software) and constructed a multivalent epitope DNA vaccine (CRPVE1ep1-5). CRPVE1ep1-5 and a control DNA vaccine (Ub3) were then delivered intracutaneously onto normal and HLA-A2.1 transgenic rabbits, respectively, by a helium-driven gene-gun delivery system. One, two or three immunizations were given to different groups of animals from both New Zealand White outbred and EIII/JC inbred genetic background. Two and three immunizations with CRPVE1ep1-5 DNA vaccine provided complete protection against viral DNA infection of HLA-A2.1 transgenic rabbits from both genetic backgrounds but not in the control-vaccinated groups. One immunization, however, failed to protect HLA-A2.1 transgenic rabbits against viral DNA infection. This study further demonstrated that the HLA-A2.1 transgenic rabbits can be used to test the immunogenicity of HLA-A2.1 restricted epitopes identified by MHCI epitope predication software. (c) 2007 Elsevier Ltd. All rights reserved.

关键词： CRPVE1 epitope DNA vaccine HLA-A2.1 transgenic rabbit vaccination protective immunity

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Pharmacogenomics of anesthetic drugs in transgenic LQT1 and LQT2 rabbits reveal genotype-specific differential effects on cardiac repolarization

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AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY 2008年第6期295卷 H2264-H2272页

作者： Odening, Katja E. Hyder, Omar Chaves, Leonard Schofield, Lorraine Brunner, Michael Kirk, Malcolm Zehender, Manfred peng, xuwen Koren, Gideon Brown Univ Warren Alpert Med Sch Rhode Isl Hosp Cardiovasc Res CtrDiv Cardiol Providence RI 02903 USA Univ Freiburg Innere Med 3 D-7800 Freiburg Germany Penn State Univ Coll Med Dept Comparat Med Hershey PA USA

Odening KE, Hyder O, Chaves L, Schofield L, Brunner M, Kirk M, Zehender M, peng X, Koren G. Pharmacogenomics of anesthetic drugs in transgenic LQT1 and LQT2 rabbits reveal genotype-specific differential effects on cardiac repolarization. Am J Physiol Heart Circ Physiol 295: H2264-H2272, 2008. First published October 3, 2008;doi: 10.1152/ajpheart. 00680.2008. Anesthetic agents prolong cardiac repolarization by blocking ion currents. However, the clinical relevance of this blockade in subjects with reduced repolarization reserve is unknown. We have generated transgenic long QT syndromes type 1 (LQT1) and type 2 (LQT2) rabbits that lack slow delayed rectifier K+ currents (I-Ks) or rapidly activating K+ currents (I-Kr) and used them as a model system to detect the channel-blocking properties of anesthetic agents. Therefore, LQT1, LQT2, and littermate control (LMC) rabbits were administered isoflurane, thiopental, midazolam, propofol, or ketamine, and surface ECGs were analyzed. Genotype-specific heart rate correction formulas were used to determine the expected QT interval at a given heart rate. The QT index (QTi) was calculated as percentage of the observed QT/expected QT. Isoflurane, a drug that blocks I-Ks, prolonged the QTi only in LQT2 and LMC but not in LQT1 rabbits. Midazolam, which blocks inward rectifier K+ current (I-Ks), prolonged the QTi in both LQT1 and LQT2 but not in LMC. Thiopental, which blocks both I-Ks and I-K1, increased the QTi in LQT2 and LMC more than in LQT1. By contrast, ketamine, which does not block I-Kr, I-Ks, or I-K1, did not alter the QTi in any group. Finally, anesthesia with isoflurane or propofol resulted in lethal polymorphic ventricular tachycardia (pVT) in three out of nine LQT2 rabbits. Transgenic LQT1 and LQT2 rabbits could serve as an in vivo model in which to examine the pharmacogenomics of drug-induced QT prolongation of anesthetic agents and their proarrhythmic potential. Transgenic LQT2 rabbits developed pVT under isoflurane an

关键词： repolarization reserve long QT syndrome types 1 and 2 sudden cardiac death ventricular fibrillation

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Transgenic LQT1 and LQT2 rabbits provide a new model for safety screening for I Kr or I Ks blocking propensity of drugs

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Journal of Pharmacological and Toxicological Methods 2008年第2期58卷 148-149页

作者： Katja E. Odening Malcolm Kirk Peem Lorvidhaya Michael Brunner Omar Hyder Jason Centracchio Lorraine Schofield Tammy Donahay Lenny Chaves xuwen peng Manfred Zehender Gideon Koren Cardiovascular Research Center RIH Brown Medical School Providence RI USA

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