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Tenofovir vs lamivudine plus adefovir in chronic hepatitis B:TENOSIMP-B study

World Journal of Gastroenterology 2017年第41期23卷 7459-7469页

作者： Manuel Rodríguez Juan Manuel Pascasio Enrique Fraga Javier Fuentes Martín Prieto Gloria Sánchez-Antolín jose Luis Calleja Esther Molina María Luisa García-Buey María Angeles Blanco Javier Salmerón María Lucía Bonet jose antonio pons jose Manuel González Miguel Angel Casado Francisco Jorquera 无 Division of Gastroenterology and Hepatology.Hospital Universitario Central de Asturias Unit for the Clinical Management of Digestive Diseases IBISHospital Universitario Virgen del Rocío Liver Transplantation and Hepatology Unit Gastroenterology ServiceHospital Universitario Reina Sofía Digestive Medicine Service Hospital Universitario Miguel Servet Hepatology Unit Digestive Medicine ServiceHospital Universitari i Politècnic La Fe Hepatology Unit Hospital Universitario Rio Hortega Liver Unit Hospital Universitario Puerta de Hierro de MajadahondaUniversidad Autónoma de Madrid Digestive Medicine Service Hospital Clínico de Santiago de Compostela Liver Unit Hospital Universitario de La Princesa Digestive Medicine Service Hospital General Universitario Gregorio Maranon Digestive Medicine Unit Complejo Hospitalario de Granada Digestive Medicine Service Hospital Universitario Son Espases Hepatology Unit IMIB Hospital Universitario Virgen de la Arrixaca Digestive Medicine Service Hospital Clínico Universitario de Valladolid Pharmacoeconomics and Outcomes Research Iberia Division of Gastroenterology and Hepatology Complejo Asistencial Universitario de León the TENOSIMP-B Research Group

AIM To demonstrate the non-inferiority(15% non-inferiority limit) of monotherapy with tenofovir disoproxil fumarate(TDF) vs the combination of lamivudine(LAM) plus adefovir dipivoxil(ADV) in the maintenance of virologic response in patients with chronic hepatitis B(CHB) and prior failure with *** This study was a Phase IV prospective, randomized, open, controlled study with 2 parallel groups(TDF and LAM+ADV) of adult patients with hepatitis B e antigen(HBe Ag)-negative CHB, prior failure with LAM, on treatment with LAM+ADV for at least 6 mo, without prior resistance to ADV and with an undetectable viral load at the start of the study, in 14 Spanish hospitals. The follow-up time for each patient was 48 wk after randomization, with quarterly visits in which the viral load, biochemical and serological parameters, adverse effects, adherence to treatment and consumption of hospital resources were *** Forty-six patients were evaluated [median age: 55.4 years(30.2-75.2); 84.8% male], including 22 patients with TDF and 24 with LAM+ADV. During study development, hepatitis B virus DNA(HBV-DNA) remained undetectable, all patients remained HBe Ag negative, and hepatitis B surface antigen(HBs Ag) positive. Alanine aminotransferase(ALT) values at the end of the study were similar in the 2 groups(25.1± 7.65, TDF vs 24.22 ± 8.38, LAM+ADV, P = 0.646). No significant changes were observed in creatinine or serum phosphorus values in either group. No significant differences between the 2 groups were noted in the identification of adverse effects(AEs)(53.8%, TDF vs 37.5%, LAM+ADV, P = 0.170), and none of the AEs which occurred were serious. Treatment adherence was 95.5% and 83.3% in the TDF and the LAM+ADV groups, respectively(P = 0.488). The costs associated with hospital resource consumption were significantly lower with the TDF treatment than the LAM+ADV treatment(€4943 ± 1059 vs €5811 ± 1538, respectively, P < 0.001).CONCLUSION TDF monotherapy proved to be safe

关键词： Tenofovir Lamivudine+Adefovir Efficacy Safety Adherence Costs Hepatitis B

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Brent *** Texas Intermediate in the US petro derivatives price formation

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Petroleum Science 2024年第1期21卷 729-739页

作者： Alejandro Almeida antonio A.Golpe Juan Manuel Martín-Alvarez jose Carlos Vides Universidad Internacional de La Rioja Department of Quantitative Methods for Economics and BusinessLa RiojaSpain University of Huelva Department of Economics and Centro de Estudios Avanzados en FisicaMatematicas y Computacion and ICEIHuelvaSpain Complutense University of Madrid Department of Applied and Structural Economics and History and ICEIMadridSpain

In this paper,we apply the spatial panel model to explore the relationship between the dynamic of two types of crude oil prices(WTI and Brent crude oil)and their refined products over *** the turbulent months of 2011,when Cushing Oklahoma had reached capacity and the crude oil export ban removal in 2015 as breakpoints,we apply this method both in the full sample and the three resultant ***,results suggest our results show that both WTI and Brent display very similar behaviour with the refined ***,when attending to each regime,results derived from the first and third regimes are quite similar to the full sample ***,during the second regime,Brent crude oil became the benchmark in the petrol market,and it influenced the distillate ***,our model can let us determine the price-setters and price-followers in the price formation mechanism through refined *** results possess important considerations to policymakers and the market participants and the price formation.

关键词： Crude oil prices Spatial panel model Refined products Price formation

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Analysing vaccine efficacy evaluated in phase 3 clinical trials carried out during outbreaks

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Infectious Disease Modelling 2024年第4期9卷 1027-1044页

作者： Francisco antonio Bezerra Coutinho Marcos Amaku Fernanda Castro Boulos jose Alfredo de Sousa Moreira Joao Italo DiasFranca Julio antonio do Amaral Eliana Nogueira Castro de Barros Claudio jose Struchiner Esper Jorge Kallas Eduardo Massad School of Medicine University of Sao PauloBrazil Instituto Butantan Sao PauloBrazil School of Applied Mathematics Fundacao Getulio VargasRio de JaneiroBrazil

In this paper we examine several definitions of vaccine efficacy(VE)that we found in the literature,for diseases that express themselves in outbreaks,that is,when the force of infection grows in time,reaches a maximum and then *** fact that the disease occurs in outbreaks results in several problems that we *** propose a mathematical model that allows the calculation of VE for several *** trials usually needs a large number of volunteers that must be ***,all volunteers should be enrolled in approximately the same time,but this is generally impossible for logistic reasons and they are enrolled in a fashion that can be replaced by a continuous density function(for example,a Gaussian function).The outbreak can also be replaced by a continuous density function,and the use of these density functions simplifies the ***,for example Gaussian functions,one of the problems one can immediately notice is that the peak of the two curves do not occur at the same *** model allows us to conclude:First,the calculated vaccine efficacy decreases when the force of infection increases;Second,the calculated vaccine efficacy decreases when the gap between the peak in the force of infection and the peak in the enrollment rate increases;Third,different trial protocols can be simulated with this model;different vaccine efficacy definitions can be calculated and in our simulations,all result are approximately the *** final,and perhaps most important conclusion of our model,is that vaccine efficacy calculated during outbreaks must be carefully examined and the best way we can suggest to overcome this problem is to stratify the enrolled volunteer's in a cohort-by-cohort basis and do the survival analysis for each cohort,or apply the Cox proportional hazards model for each cohort.

关键词： Vaccine efficacy Clinical trials Mathematical models Simulations Covid-19

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碳基固体氧化物燃料电池研究进展

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洁净煤技术 2024年第1期30卷 239-264页

作者：张伟魏嘉璐 jose antonio Alonso 孙春文中国矿业大学(北京)化学与环境工程学院北京100083 Instituto de Ciencia de los Materiales de Madrid CSICCantoblanco-Madrid 28049Spain

随着人们对绿色能源和环境友好型社会需求的日益增长,先进能量转换装置或系统的研发亟待加速,而燃料电池系统被认为是最有希望的未来发电装置。在不同种类的燃料电池中,固体氧化物燃料电池(SOFCs)是一种清洁环保的发电装置,因其独特的... 详细信息

随着人们对绿色能源和环境友好型社会需求的日益增长,先进能量转换装置或系统的研发亟待加速,而燃料电池系统被认为是最有希望的未来发电装置。在不同种类的燃料电池中,固体氧化物燃料电池(SOFCs)是一种清洁环保的发电装置,因其独特的多燃料运行能力及能量转化效率高等优点而前景广阔。然而,传统使用镍-金属陶瓷阳极的SOFCs,在碳氢化合物燃料下运行时,由于燃料的不完全氧化会使阳极产生积碳,从而导致电池性能下降。讨论了碳基SOFC中碳沉积机理和解决阳极积碳的策略,重点介绍了目前广泛研究的具有混合离子-电子导体的双金属-金属陶瓷材料的种类以及研究进展,并总结了双金属-金属陶瓷材料的抗积碳机理,主要表现为降低阳极表面的碳沉积速率以及加速积碳的去除。还介绍了在还原性气氛中,钙钛矿材料中纳米粒子原位偏析的原理,并讨论了原位偏析所形成的纳米颗粒以及其与钙钛矿主体所形成的金属氧化物异质结构在抗积碳阳极中的应用。此外,还探究了多层阳极和单原子催化剂阳极在中温SOFCs中的应用。在燃料电池技术巨大进步的推动下,人们对可用于固定式发电的集成煤气化的燃料电池发电系统(IGFCs)产生了新的兴趣,该系统对于实现煤炭的清洁高效利用具有重要意义,该技术的关键依托于SOFCs的成熟度。最后,总结并指出了碳基SOFCs未来的一些研究方向。

关键词：固体氧化物燃料电池阳极材料碳氢燃料碳沉积整体煤气化燃料电池

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Multi-tissue transcriptomics of a unique monozygotic discordant twin case of severe progressive osseous heteroplasia

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Genes & Diseases 2024年第3期11卷 22-25页

作者： Alberto Gomez-Carballa Maria jose Curras-Tuala Sara Pischedda Miriam Cebey-Lopez jose Gomez-Rial Irene Rivero-Cale Jacobo Pardo-seco Xabier Bello Sandra Viz-Lasheras antonio Justicia-Grande Julian Montoto-Louzao Alba Camino-Mera Isabel Ferreiros-Vidal Maximo Fraga jose RAntunez Rodolfo Gomez Federico Martinon-Torres antonio Salas Genetics Vaccines and Infections Research Group(GENVIP)Instituto de Investigacion Sanitaria de SantiagoSantiagode CompostelaGalicia 15706Spain Translational Pediatrics and Infectious Diseases Department of PediatricsHospital Clinico Universitario de Santiago de CompostelaServicio Galego de Saude(SERGAS)Galicia 15706Spain Laboratorio de Inmunologia Servicio de Andlisis ClinicosHospital Clinico Universitario de Santiago de CompostelaServicio Galego de Saude(SERGAS)Galicia 15706Spain Unidade de Xenetica Instituto de Ciencias Forenses(INCIFOR)Facultade de MedicinaUniversidade de Santiago de Compostelaand GenPoB Research GroupInstituto de Investigacion SanitariaHospital Clinico Universitario de Santiago de CompostelaServicio Galego de Saude(SERGAS)Galicia 15706Spain Musculoskeletal Pathology Group Instituto de Investigacion Sanitaria de SantiagoServicio Galego de Saude(SERGAS)Santiago de CompostelaGalicia 15706Spain Department of Pathology Hospital Clinico Universitario de Santiago de Compostela(SERGAS)Galicia 15706Spain Unidad Integrada de BiobancosBiomodelos 3D y Modelos Animales IDIS(lnstituto de Investigacion Sanitaria de Santiagode Compostela)Galicia15706Spain Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias(CIBER-ES) MadridSpain

Progressive osseous heteroplasia(POH)is an ultra-rare autosomal dominant disabling disorder characterized by heterotopic ossification(HO).It is caused by heterozygous inactivating mutations in the GNAS(guanine nucleotide-binding protein alpha-stimulating activity polypeptide)***,the molecular mechanisms underlying HO remain poorly *** a treatment for POH is not yet available,the identification of the mechanisms driving POH in affected tissues using gene expression may be of great help to underestand the molecular basis of POH and develop new therapeutic approaches.

关键词： stimulating driving asi

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Effectiveness and safety of first-generation protease inhibitors in clinical practice:Hepatitis C virus patients with advanced fibrosis

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World Journal of Gastroenterology 2015年第30期21卷 9163-9174页

作者： Javier Salmeron Carmen Vinaixa Ruben Berenguer Juan Manuel Pascasio Juan jose Sanchez Ruano Miguel angel Serra Ana Gila Moises Diago Manuel Romero-Gomez jose Maria Navarro Milagros Testillano Conrado Fernandez Dolores Espinosa Isabel Carmona jose antonio pons Francisco Jorquera Francisco Javier Rodriguez Ramon Perez jose Luis Montero Rafael Granados Miguel Fernandez Ana Belen Martin Paloma Munoz de Rueda Rosa Quiles CIBERehd Instituto de Salud Carlos Ⅲ28029 MadridSpain Unit for Clinical Management of Digestive Diseases Complejo Hospitalario Universitario de Granada Instituto de Investigacion Biosanitaria de Granada University Hospital Politecnico La Fe Unit for Clinical Management of Digestive Diseases University Hospital Virgen Del Rocio Hospital Toledo University Clinic Hospital of Valencia University General Hospital of Valencia Unit for Clinical Management of Digestive Diseases University Hospital Nuestra Senora de Valme Department of Gastroenterology and Hepatology Agencia Sanitaria Costa del Sol University Hospital Cruces Gastroenterology Unit University Hospital Fundacion Alcorcon University Hospital Virgen Macarena University Hospital Virgen de la Arrixaca Hospital of Leon University General Hospital Reina Sofia Department Gastroenterology and Hepatology University Hospital Central de Asturias University Hospital Reina Sofia University Hospital De Gran Canaria Dr. Negrin Hospital San Pedro de Alcantara

AIM:To evaluates the effectiveness and safety of the first generation,NS3/4A protease inhibitors(PIs) in clinical practice against chronic C virus,especially in patients with advanced fibrosis. METHODS:Prospective study and non-experimental analysis of a multicentre cohort of 38 Spanish hospitals that includes patients with chronic hepatitis C genotype 1,treatment-na?ve(TN) or treatment-experienced(TE),who underwent triple therapy with the first generation NS3/4A protease inhibitors,boceprevir(BOC) and telaprevir(TVR),in combination with pegylated interferon and ribavirin. The patients were treatment in routine practice settings. Data on the study population and on adverse clinical and virologic effects were compiled during the treatment period and during follow ***:One thousand and fifty seven patients were included,405(38%) were treated with BOC and 652(62%) with TVR. Of this total,30%(n = 319) were TN and the remaining were TE:28%(n = 298) relapsers,12%(n = 123) partial responders(PR),25%(n = 260) null-responders(NR) and for 5%(n = 57) with prior response unknown. The rate of sustained virologic response(SVR) by intention-to-treatment(ITT) was greater in those treated with TVR(65%) than in those treated with BOC(52%)(P ponse(51%):this outcome was

关键词： Hepatitis C Boceprevir Telaprevir First-generation protease inhibitors Advanced fibrosis

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New therapeutic strategy with extracorporeal membrane oxygenation for refractory hepatopulmonary syndrome after liver transplant: A case report

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World Journal of Transplantation 2024年第1期14卷 210-214页

作者： Belinda Sánchez Pérez María Pérez Reyes jose Aranda Narvaez Julio Santoyo Villalba jose antonio Perez Daga Claudia Sanchez-Gonzalez Julio Santoyo-Santoyo Hepatobiliary and Trasplantation Unit General and Digestive Surgery DepartmentUniversity Regional HospitalMalaga 29010Spain Department of General and Digestive Surgery Regional University Hospital of MalagaMalaga 29010Spain

BACKGROUND Due to the lack of published literature about treatment of refractory hepatopulmonary syndrome(HPS)after liver transplant(LT),this case adds information and experience on this issue along with a treatment with positive *** is a complication of end-stage liver disease,with a 10%-30%incidence in cirrhotic *** can reverse the physiopathology of this process and restore normal ***,in some cases,refractory hypoxemia persists,and extracorporeal membrane oxygenation(ECMO)can be used as a rescue therapy with good *** SUMMARY A 59-year-old patient with alcohol-related liver cirrhosis and portal hypertension was included in the LT waiting list for *** had good liver function(Model for End-Stage Liver Disease score 12,Child-Pugh class B7).He had pulmonary fibrosis and a mild restrictive respiratory pattern with a basal oxygen saturation of 82%.The macroaggregated albumin test result was>*** demonstrated a forced expiratory volume in one second(FEV1)of 78%,forced vital capacity(FVC)of 74%,FEV1/FVC ratio of 81%,diffusion capacity for carbon monoxide of 42%,and carbon monoxide transfer coefficient of 57%.He required domiciliary oxygen at 2 L/min(16 h/d).The patient was admitted to the intensive care unit(ICU)and extubated in the first 24 h,needing high-flow therapy and non-invasive ventilation and inhaled nitric oxide *** was needed after 72 *** to the non-response to supportive therapies,installation of ECMO was decided with progressive recovery after 9 *** was possible on the tenth day,maintaining a high-flow nasal cannula and de-escalating to conventional oxygen therapy after 48 *** was discharged from ICU on postoperative day(POD)20 with a 90%-92%oxygen *** recycling was needed twice for acute *** patient was discharged from hospital on POD 27 with no symptoms,with an 89%-90%oxygen *** Due to the favorable results observed,ECMO could bec

关键词： Liver transplantation Hepatopulmonary syndrome Refractory hypoxemia Treatment Extracorporeal membrane oxygenation Case report

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Plant cell wall-mediated disease resistance:Current understanding and future perspectives

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Molecular Plant 2024年第5期17卷 699-724页

作者： antonio Molina Lucıa Jorda Miguel Angel Torres Marina Martın-Dacal Diego jose Berlanga Patricia Fernandez-Calvo Elena Gomez-Rubio Sonsoles Martın-Santamarıa Centro de Biotecnología y Genómica de Plantas Universidad Politécnica de Madrid(UPM)-Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria(INIA/CSIC)Campus de Montegancedo UPMPozuelo de Alarcon(Madrid)Spain Departamento de Biotecnologıa-Biología Vegetal Escuela Técnica Superior de Ingenierıa AgronomicaAlimentarıa y de BiosistemasUPMMadridSpain Centro de Investigaciones Biologicas Margarita Salas Consejo Superior de Investigaciones Científicas(CSIC)Ramiro de Maeztu 928040 MadridSpain Misión Biológica de Galicia Consejo Superior de Investigaciones Científicas(CSIC)Campus de Montegancedo UPMPozuelo de Alarcón(Madrid)Spain

Beyond their function as structural barriers,plant cell walls are essential elements for the adaptation of plants to environmental *** walls are dynamic structures whose composition and integrity can be altered in response to environmental challenges and developmental *** wall changes are perceived by plant sensors/receptors to trigger adaptative responses during development and upon stress *** cell wall damage caused by pathogen infection,wounding,or other stresses leads to the release of wall molecules,such as carbohydrates(glycans),that function as damage-associated molecular patterns(DAMPs).DAMPs are perceived by the extracellular ectodomains(ECDs)of pattern recognition receptors(PRRs)to activate pattern-triggered immunity(PTI)and disease ***,glycans released from the walls and extracellular layers of microorganisms interacting with plants are recognized as microbe-associated molecular patterns(MAMPs)by specific ECD-PRRs triggering PTI *** number of oligosaccharides DAMPs/MAMPs identified that are perceived by plants has increased in recent ***,the structural mechanisms underlying glycan recognition by plant PRRs remain ***,this knowledge is mainly focused on receptors of the LysM-PRR family,which are involved in the perception of various molecules,such as chitooligosaccharides from fungi and lipo-chitooligosaccharides(i.e.,Nod/MYC factors from bacteria and mycorrhiza,respectively)that trigger differential physiological ***,additional families of plant PRRs have recently been implicated in oligosaccharide/polysaccharide *** include receptor kinases(RKs)with leucine-rich repeat and Malectin domains in their ECDs(LRR-MAL RKs),Catharanthus roseus RECEPTOR-LIKE KINASE 1-LIKE group(CrRLK1L)with Malectin-like domains in their ECDs,as well as wall-associated kinases,lectin-RKs,and *** characterization of structural basis of glycans recogniti

关键词： Arabidopsis thaliana cell wall damage-associated molecular patterns DAMPs disease resistance glycans oligosaccharides pattern-triggered immunity PTl pattern recognition receptor PRRs

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Multi-omic study to unmask genes involved in prostate cancer development in amulti-case family

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Cancer Communications 2024年第3期44卷 443-447页

作者： Lucia Chica-Redecillas Sergio Cuenca-Lopez Eduardo Andres-Leon Laura Carmen Terron-Camero Blanca Cano-Gutierrez jose Manuel Cozar jose antonio Lorente Fernando Vazquez-Alonso Luis Javier Martinez-Gonzalez Maria Jesus Alvarez-Cubero GENYO Centre for Genomics and Oncological ResearchPfizerUniversity of GranadaAndalusian Regional GovernmentPTS GranadaGranadaGranadaSpain Department of Biochemistry Molecular Biology III and ImmunologyFaculty of MedicineUniversity of GranadaPTS GranadaGranadaGranadaSpain Bioinformatics Unit Institute of Parasitology and Biomedicine“López-Neyra”Spanish National Research CouncilGranadaGranadaSpain Nursery Service.University Hospital Clínico San Cecilio GranadaGranadaSpain Urology Department University Hospital Virgen de las NievesGranadaGranadaSpain Legal Medicine and Toxicology Department Faculty of MedicineUniversity of GranadaPTS GranadaGranadaGranadaSpain Ibs Biosanitary Research InstituteGranadaGranadaSpain

Dear Editor,Hereditary prostate cancer(PC)comprises 5%-10%of all PC *** increased risk of PC in menwith a family his-tory of the disease is well known and is commonly caused by germline mutations,leading to clinical guidelines men-tioning various genes for identifying high-risk ***,the complex inheritance patterns involvingmul-tiple single nucleotide polymorphisms(SNPs)make it a genetically heterogeneous disease,with genetic testing still in its early stages.

关键词： cancer clinical cases

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High-repetition-rate source of nanosecond duration kA-current pulses driven by relativistic laser pulses

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High Power Laser Science and Engineering 2024年第3期12卷 106-115页

作者： Michael Ehret Jakub Cikhardt Philip Wykeham Bradford Iuliana-Mariana Vladisavlevici Tomas Burian Diego de Luis jose Luis Henares Rubén Hernández Martín Jon Imanol Apiñaniz Roberto Lera Joséantonio Pérez-Hernández João Jorge Santos Giancarlo Gatti Centro de Láseres Pulsados(CLPU) VillamayorSpain Czech Technical University in Prague Faculty of Electrical EngineeringPragueCzech Republic Univ.Bordeaux-CNRS-CEA Centre Lasers Intenses et Applications(CELIA)UMR 5107TalenceFrance Department of Radiation and Chemical Physics FZU-Institute of Physics of the Czech Academy of SciencesPragueCzech Republic

We report the first high-repetition-rate generation and simultaneous characterization of nanosecond-scale return currents of kA-magnitude issued by the polarization of a target irradiated with a PW-class high-repetition-rate titanium:sapphire laser system at relativistic *** present experimental results obtained with the VEGA-3 laser at intensities from5×10^(18)to 1.3×10^(20)W cm^(-2).A non-invasive inductive return-current monitor is adopted to measure the derivative of return currents of the order of kA ns-1and analysis methodology is developed to derive return *** compare the current for copper,aluminium and Kapton targets at different laser *** data show the stable production of current peaks and clear prospects for the tailoring of the pulse shape,which is promising for future applications in highenergy-density science,for example,electromagnetic interference stress tests,high-voltage pulse response measurements and charged particle beam *** compare the target discharge of the order of hundreds of nC with theoretical predictions and a good agreement is found.

关键词： current pulses electromagnetic pulse application high-power laser relativistic laser plasma

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