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Endosomal escape of protein nanoparticles engineered through humanized histidine-rich peptides

Science China Materials 2020年第4期63卷 644-653页

作者： Hector Lopez-Laguna rafael Cubarsi Ugutz Unzueta Ramon Mangues Esther Vazquez Antonio Villaverde Institut de Biotecnologia i de Biomedicina Universitat Aut6noma de BarcelonaBellaterra08193 BarcelonaSpain Departament de Genetica i de Microbiologia Universitat Aut6noma de BarcelonaBellaterra08193 BarcelonaSpain CIBER de Bioingenieria Biomateriales y Nanomedicina(CIBER-BBN)C/Monforte de Lemos 3-528029 MadridSpain Departament de Matematiques Universitat Politecnica de Catalunya08034BarcelonaSpain Institut d'Investigacions Biomediques Sant Pau Hospital de la Santa Creu i Sant Pau08025 BarcelonaSpain

Poly-histidine peptides such as H6(HHHHHH)are used in protein biotechnologies as purification tags,protein-assembling agents and endosomal-escape *** pleiotropic properties of such peptides make them appealing to design protein-based smart materials or nanoparticles for imaging or drug delivery to be produced in form of recombinant ***,the clinical applicability of H6-tagged proteins is restricted by the potential immunogenicity of these *** this study,we have explored several humanized histidine-rich peptides in tumor-targeted modular proteins,which can specifically bind and be internalized by the target cells through the tumoral marker *** were particularly interested in exploring how protein purification,self-assembling and endosomal escape perform in proteins containing the variant histidine-rich *** the tested candidates,the peptide H5 E(HEHEHEHEH)is promising as a good promoter of endosomal escape of the associated fulllength protein upon endosomal *** numerical modelling of cell penetration and endosomal escape of the tested proteins has revealed a negative relationship between the amount of protein internalized into target cells and the efficiency of cytoplasmic *** fact demonstrates that the His-mediated,proton sponge-based endosomal escape saturates at moderate amounts of internalized protein,a fact that might be critical for the design of protein materials for cytosolic molecular delivery.

关键词： protein materials nanoparticles genetic design endosomal escape poly-histidines

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Determination of the ground vibration attenuation law from a singleblast: A particular case of trench blasting

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Journal of Rock Mechanics and Geotechnical Engineering 2021年第5期13卷 1182-1192页

作者： rafael Rodríguez Laura García de Marina Marc Bascompta Cristóbal Lombardía Department of Mining Exploitation and Prospecting School of MiningEnergy and Materials EngineeringUniversity of OviedoIndependencia 13Oviedo33004Spain Department of Mining Industrial and ICT EngineeringPolytechnic University of Catalonia(UPC)ManresaAv.Bases de Manresa61-73Barcelona08242Spain Perforaciones Noroeste S.A Longoria Carbajal No.3Oviedo33004Spain

The general transmissivity law of ground vibrations was studied,and a user-friendly methodology for determining the behavior of vibrations generated in any rock mass is *** study was based on a single blast in a trench excavation,analyzing the vibration components recorded from two fixed *** attenuation law and the main variables according to the legal requirements,frequency and peak particle velocity(PPV),are defined with this novel method,achieving a high confidence level in a simple *** proposed approach can also have an important impact in terms of reducing the potential consequences of vibrations for the surrounding construction and achieving the required definition of rock *** the cost and time in many projects where blasting techniques are applied is particularly useful for the design of future blasts.

关键词： Empirical analysis Blasting Ground vibration Trenching Wave propagation

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Solution of the Center Problem for a Class of Polynomial Differential Systems

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Acta Mathematica Sinica,English Series 2024年第7期40卷 1685-1696页

作者： Chang Jian Liu Jaume Llibre rafael Ramírez Valentín Ramírez School of Mathematics(Zhuhai) Sun Yat-sen UniversityZhuhai519086P.R.China Departament de Matemàtiques Universitat Autònoma de Barcelona08193BellaterraBarcelonaCataloniaSpain Departament d’Enginyeria Informàtica i Matemàtiques Universitat Rovira i VirgiliAvinguda dels Paiïsos Catalans 2643007TarragonaCataloniaSpain

Consider the polynomial differential system of degree m of the form x=-y(1+μ(a_(2)x-a_(1)y))+x(v(a_(1)x+a_(2)y)+Ω_(m-1)(x,y)),y=x(1+μ(a_(2)x-a_(1)y))+y(v(a_(1)x+a_(2)y)+Ω_(m-1)(x,y)),whereμandνare real numbers such that(μ^(2)+v^(2))(μ+v(m-2))(a_(1)^(2)+a_(2)^(2))≠m>2 andΩ_(m−1)(x,y)is a homogenous polynomial of degree m−1.A conjecture,stated in *** Equations 2019,suggests that whenν=1,this differential system has a weak center at the origin if and only if after a convenient linear change of variable(x,y)→(X,Y)the system is invariant under the transformation(X,Y,t)→(−X,Y,−t).For every degree m we prove the extension of this conjecture to any value ofνexcept for a finite set of values ofμ.

关键词： Center problem polynomial differential system

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Validation of a steel dual-core self-centering brace （DC-SCB） for seismic resistance： from brace member to one-story one-bay braced frame tests

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Frontiers of Structural and Civil Engineering 2016年第3期10卷 303-311页

作者： Chung-Che CHOU Ping-Ting CHUNG Tsung-Han WU Alexis rafael Ovalle BEATO Department of Civil Engineering Taiwan University Taipei Taiwan China Director Center for Earthquake Engineering Research (CEER) Taiwan University Taipei Taiwan China

A steel dual-core self-centering brace （DC-SCB） is an innovative structural member that provides both energy dissipation and self-centering properties to structures, reducing maximum and residual drifts of structures in earthquakes. The axial deformation capacity of the DC-SCB is doubled by a parallel arrangement of two inner cores, one outer box and two sets of tensioning elements. This paper presents cyclic test results of a DC-SCB component and a full- scale one-story, one-bay steel frame with a DC-SCB. The DC-SCB that was near 8 m-long was tested to evaluate its cyclic behavior and durability. The DC-SCB performed well under a total of three increasing cyclic loading tests and 60 low- cycle fatigue loading tests without failure. The maximum axial load of the DC-SCB was near 1700 kN at an interstory drift of 2.5%. Moreover, a three-story dual-core self-centering braced frame （DC-SCBF） with a single-diagonal DC-SCB was designed and its first-story, one-bay DC-SCBF subassembly specimen was tested in multiple earthquake-type loadings. The one-story, one-bay subassembly frame specimen performed well up to an interstory drift of 2% with yielding at the column base and local buckling in the steel beam; no damage of the DC-SCB was found after all tests. The maximum residual drift of the DC-SCBF caused by beam local buckling was 0.5% in 2.0% drift cycles.

关键词： dual-core self-centering brace (DC-SCB) braced frame tests residual deformation

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Complex hepatic outflow reconstruction in domino liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2014年第1期13卷 98-100页

作者： rafael S Pinheiro Quirino Lai Carola Dahrenmoller Jan Lerut Starzl Unit of Abdominal Transplantation University Hospitals Saint Luc Université Catholique Louvain UCL Brussels Belgium Department of Gastroenterology So Paulo University School of Medicine So Paulo Brazil

Domino liver transplantation has been accepted as a safe procedure to further expand the organ donor pool. The most important technical challenge of the procedure resides in restoring a proper hepatic venous allograft outflow in the familial amyloidotic polyneuropathy-liver recipient. To overcome this issue, combined techniques were used to perform an innovative outflow reconstruction. A domino liver transplantation was successfully performed with reconstruction of complex venous outflow. The inferior vena cava sparing hepatectomy technique in the familial amyloidotic polyneuropathy-donor was used to cut the hepatic vein to the liver parenchyma. To overcome this issue the venous outflow tract was reconstructed using a longitudinally opened iliac vein graft from a post-mortem donor to create a new outflow tract using a diamond patch between the right and middle/left hepatic veins.

关键词： liver transplantation intraoperative anatomy hepatic vein

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Human sperm chromatin epigenetic potential： genomics, proteomics, and male infertility

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Asian Journal of Andrology 2015年第4期17卷 601-609页

作者： ludit Castillo Josep Maria Estanyol Josep Lluis Ballesca rafael Oliva Human Genetics Research Group IDIBAPS Faculty of Medicine University of Barcelona Casanova 143 08036 Barcelona Spain Biochemistry and Molecular GeneticsService Biomedical Diagnostic Centre Hospital Clinic Villarroel 170 08036 Barcelona Spain Proteomics Unit Scientific and Technological Centres of the Universityof Barcelona (CCiTUB) Casanova 143 08036 Barcelona Spain Clinic Institute of Gynaecology Obstetrics and Neonatology Hospital Clinic Villarroel 170 08036Barcelona Spain.

The classical idea about the function of the mammalian sperm chromatin is that it serves to transmit a highly protected and transcriptionally inactive paternal genome, largely condensed by protamines, to the next generation. In addition, recent sperm chromatin genome-wide dissection studies indicate the presence of a differential distribution of the genes and repetitive sequences in the protamine-condensed and histone-condensed sperm chromatin domains, which could be potentially involved in regulatory roles after fertilization. Interestingly, recent proteomic studies have shown that sperm chromatin contains many additional proteins, in addition to the abundant histones and protamines, with specific modifications and chromatin affinity features which are also delivered to the oocyte. Both gene and protein signatures seem to be altered in infertile patients and, as such, are consistent with the potential involvement of the sperm chromatin landscape in early embryo development. This present work reviews the available information on the composition of the human sperm chromatin and its epigenetic potential, with a particular focus on recent results derived from high-throughput genomic and proteomic studies. As a complement, we provide experimental evidence for the detection of phosphorylations and acetylations in human protamine 1 using a mass spectrometry approach. The available data indicate that the sperm chromatin is much more complex than what it was previously thought, raising the possibility that it could also serve to transmit crucial paternal epigenetic information to the embryo.

关键词： genomics male infertility proteomics sperm chromatin sperm epigenetics

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Cooperative Virus-Virus Interactions:An Evolutionary Perspective

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BioDesign Research 2022年第1期2022卷 111-123页

作者： Ernesto Segredo-Otero rafael Sanjuán Institute for Integrative Systems Biology(I2SysBio) Consejo Superior de Investigaciones Científicas-Universitat de ValènciaC/Catedrático Agustín Escardino 946980 PaternaValènciaSpain

Despite extensive evidence of virus-virus interactions,not much is known about their biological ***,virusvirusinteractions could have evolved as a form of cooperation or simply be a by-product of other ***,we review anddiscuss different types of virus-virus interactions from the point of view of social evolution,which provides a well-establishedframework for interpreting the fitness costs and benefits of such *** also classify interactions according to theirmechanisms of action and speculate on their evolutionary *** in any other biological system,the evolutionarystability of viral cooperation critically requires cheaters to be excluded from cooperative *** discuss how cheaterviruses exploit cooperative traits and how viral populations are able to counteract this maladaptive process.

关键词： interpreting spite classify

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Degradation of indomethacin in river water under stress and non-stress laboratory conditions:degradation products,long-term evolution and adsorption to sediment

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Journal of Environmental Sciences 2017年第1期29卷 13-20页

作者： Juan J.Jimenez Maria I.Sanchez rafael Pardo Beatriz E.Munoz Department of Analytical Chemistry Faculty of SciencesCampus Miguel DelibesUniversity of ValladolidPaseo de Belen 747012 ValladolidSpain I.U.CINQUIMA Campus Miguel DelibesUniversity of ValladolidPaseo de Belen 547011 ValladolidSpain Department of Analytical Chemistry School of Industrial EngineersUniversity of ValladoliclFrancisco Mendizdbal 147014 ValladolidSpain

The pharmaceutical compound indomethacin is not totally removed in wastewater treatment plants,whose effluents flow into aquatic environments;concentrations in the 0.1-100 ng/L range are commonly found in surface waters,and its fate is ***,biological,photochemical and thermal degradation assays were conducted under stress and non-stress conditions to estimate its degradation rate in river water and establish its degradation products over *** results revealed that direct sunlight irradiation promoted the complete degradation of indomethacin（2 μg/L） in less than 6 hr,but indomethacin was detected over a period of 4 months when water was kept under the natural day-night cycle and the exposure to sunlight was partially limited,as occurs inside a body of *** biological degradation in water was negligible,while the hydrolysis at pH 7.8 was *** were monitored by ultra-pressure liquid chromatography/quadrupole time-of-flight/mass spectrometry after solid-phase extraction,and six degradation products were found;their structures were proposed based on the molecular formulae and fragmentation observed in high-resolution tandem mass spectra.4-Chlorobenzoic and 2-acetamido-5-methoxybenzoic acids were the long-term transformation products,persisting for at least 30 weeks in water kept under non-stress ***,the degradation in the presence of sediment was also monitored over time,with some differences being *** adsorption coefficients of indomethacin and degradation products on river sediment were calculated;long-term degradation products did not have significant adsorption to sediment.

关键词： Indomethacin Degradation products River water Adsorption coefficients High-resolution mass spectrometry

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Diagnostic value of sperm DNA fragmentation and sperm high-magnification for predicting outcome of assisted reproduction treatment

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Asian Journal of Andrology 2013年第6期15卷 790-794,I0008-I0009页

作者： Gemma López rafael Lafuente Miguel A Checa Ramón Carreras Mario Brassesco Centre de Infertilidad y Reproduccion Humana (ClRH) E-08017 Barcelona Spain Department of Obstetrics and Gynecology Hospital Universitari del Mar Universitat AutOnoma de Barcelona E-08003 Barcelona Spain

Over the last years, major improvements in the field of male infertility diagnosis have been achieved. The aim of this study was to determine the diagnostic usefulness of sperm DNA integrity and sperm vacuolisation for predicting outcome in infertile couples undergoing in vitroferti lisation （IVF） and intracytoplasmic sperm injection （ICSI） treatments. A cohort study from 152 infertile couples undergoing sperm DNA fragmentation and high-magnification tests prior to an assisted reproduction treatment was designed. We found that the most predictive cutoff for pregnancy was 25.5% of DNA fragmentation with a negative predictive value of 72.7% （P=0.02）. For the degree of vacuolisation, the best predictor of pregnancy was 73.5% of vacuolated sperm grades Ⅲ ＋ Ⅳ with a negative predictive value of 39.4% （P=0.09）, which was not statistically significant. In conclusion, sperm DNA fragmentation greater than 25.5% could be associated with higher probability of failure IVF treatment. Regarding the results of the sperm analysis at high magnification, they do not allow us to predict whether or not oatients will become pregnant.

关键词： DNA fragmentation high-magnification IVF vacuoles

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Endothelial nitric oxide synthase regulation is altered in pancreas from cirrhotic rats

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World Journal of Gastroenterology 2006年第2期12卷 228-233页

作者： Jean-Louis Frossard rafael Quadri Antoine Hadengue Philippe Morel Catherine M Pastor Division de Gastroenterologie Hpitaux Universitaires de Geneve Departement de Chirurgie Hopitaux Universitaires de Geneve Laboratoire de Physiopathologie Hepatique et Imagerie Moleculaire Hpitaux Universitaires de Geneve

AIM： To determine whether biliary cirrhosis could induce pancreatic dysfunction such as modifications in endothelial nitric oxide synthase（eNOS） expression and whether the regulation of eNOS could be altered by the regulatory proteins caveolin and heat shock protein 90 （Hsp90）, as well as by the modifications of calmodulin binding to eNOS. METHODS： Immunoprecipitations and Western blotting analysis were performed in pancreas isolated from sham and cirrhotic rats. RESULTS： Pancreatic injury was minor in cirrhotic rats but eNOS expression importantly decreased with the length （and the severity） of the disease. Because coimmunoprecipitation of eNOS with both Hsp90 and caveolin similarly decreased in cirrhotic rats, eNOS activity was not modified by this mechanism. In contrast, drrhosis decreased the calmodulin binding to eNOS with a concomitant decrease in eNOS activity. CONCLUSION： In biliary cirrhosis, pancreatic injury is minor but the pancreatic nitric oxide （NO） production is significantly decreased by two mechanisms： a decreased expression of the enzyme and a decreased binding of calmodulin to eNOS.

关键词： Pancreas Biliary cirrhosis Endothelial NO synthase Caveolin Heat shock protein 90

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