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Study and ICH validation of a reverse-phase liquid chromatographic method for the quantification of the intact monoclonal antibody cetuximab

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Journal of Pharmaceutical Analysis 2016年第2期6卷 117-124页

作者： antonio martinez-Ortega Agustin Herrera antonio Salmeron-garcia Jose Cabeza luis Cuadros-Rodriguez Natalia Navas Department of Analytical Chemistry University of Granada Faculty of Science Campus Fuentenueva s/n E-18071 Granada Spain UgC intercentro Interniveles Farmacia granada San Cecilio Hospital Biomedical Research Institute ibs. GRANADA. Hospitales Universitarios de Granada University of Granada E-18012 Granada Spain Department of Analytical Chemistry Science Faculty Biomedical Research Institute ibis. GRANADA University of Granada Campus Fuentenuevo s/n E-18071 Granada Spain

Cetuximab （CTX） is a potent chimeric mouse/human monoclonal antibody （mAb） approved worldwide for treatment of metastatic colorectal cancer. Among the various biological and physical analyses per- formed for full study on this biopharmaceutic, the determination of the concentration preparations throughout manufacturing and subsequent handling in hospital is particularly relevant. In the present work, the study and validation of a method for quantifying intact CTX by reverse-phase high-perfor- mance liquid chromatography with diode array detection （（RP）HPLC/DAD） is presented. With that end, we checked the performance of a chromatographic method for quantifying CTX and conducted a study to validate the method as stability-indicating in accordance with the International Conference on Harmo- nization guidelines （ICH） for biotechnological drugs; therefore, we evaluated linearity, accuracy, preci- sion, detection and quantification limits, robustness and system suitability. The specificity of the method and the robustness of the mAb formulation against external stress factors were estimated by compre- hensive chromatographic analysis by subjecting CTX to several informative stress conditions. As de- monstrated, the method is rapid, accurate, and reproducible for CTX quantification. It was also suc- cessfully used to quantify CTX in a long-term stability study performed under hospital conditions.

关键词： Reverse-phase high performance liquidchromatography Diode detector Stress study Biopharmaceuticals Cetuximab

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The biosynthesis and wall-binding of hemicelluloses in cellulose-deficient maize cells:An example of metabolic plasticity

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Journal of Integrative Plant Biology 2015年第4期57卷 373-387页

作者： maría de Castro Janice g.miller José luis Acebes antonio Encina Penélope garcía-Angulo Stephen C.Fry The Edinburgh Cell Wall group Institute of Molecular Plant SciencesSchool of Biological SciencesDaniel Rutherford BuildingThe King's Buildings Laboratory of Plant Physiology Faculty of Biological and Environmental SciencesUniversity of Léon

Cell-suspension cultures（zea mays L.,Black mexican sweet corn） habituated to 2,6-dichlorobenzonitrile（DCB） survive with reduced cellulose owing to hemicellulose network modification. We aimed to de fine the hemicellulose metabolism modifications in DCB-habituated maize cells showing a mild reduction in cellulose at different stages in the culture cycle. Using pulse-chase radiolabeling, we fed habituated and non-habituated cultures with [3H]arabinose,and traced the distribution of 3H-pentose residues between xylans, xyloglucans and other polymers in several cellular compartments for 5 h. Habituated cells were slower taking up exogenous [3H]arabinose. Tritium was incorporated into polysaccharide-bound arabinose and xylose residues, but habituated cells diverted a higher proportion of their new [3H]xylose residues into（hetero） xylans at the expense of xyloglucan synthesis. During logarithmic growth, habituated cells showed slower vesicular traf ficking of polymers,especially xylans. moreover, habituated cells showed a decrease in the strong wall-binding of all pentose-containing polysaccharides studied; correspondingly, especially in log phase cultures, habituation increased the proportion of 3H-hemicelluloses（[3H]xylans and [3H]xyloglucan） sloughed into the medium. These findings could be related to the cel walls’ cellulose-deficiency, and consequent reduction in binding sites for hemicelluloses; the data could also re fl ect the habituated cells’ reduced capacity to integrate arabinox ylans by extra-protoplasmic phenolic cross-linking, as well as xyloglucans, during wall assembly.

关键词： Arabinoxylan cell wall cross-linking 2,6-dichlorobenzonitrile Hemicellulose biosynthesis xyloglucan

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化学与微生物实验室

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现代装饰 2024年第3期 62-69页

作者： Jose luis Esteban Penelas(设计) Yolanda Hernandez Lorente(设计) maria Esteban Casanas(设计) antonio guijarro(设计) marina Rodriguez Sotoca(设计) Kevin Roman Cruz(设计) Yakaterina Savina(设计) Imagen Subliminal(摄影) 舒禹(编译) 不详 miguel de guzman+Rocio Romero

建筑呈现明显的后工业美学特征,内设有一个微生物和化学分析实验室,功能设施极为复杂,使用中需要极高的功能效率与超先进的图像兼容。设计重新激活地区周围的强大工业景观,通过穿孔立面,过滤环境并生成独特的室内景观。

关键词：微生物实验室工业景观室内景观功能设施美学特征

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COVID-19 and Indirect Liver Injury:A Narrative Synthesis of the Evidence

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Journal of Clinical and Translational Hepatology 2021年第5期9卷 760-768页

作者： Francisco Idalsoaga gustavo Ayares Juan Pablo Arab luis antonio Díaz Departamento de gastroenterología Escuela de MedicinaPontificia Universidad Católica de ChileSantiagoChile Centro de Envejecimiento y Regeneración(CARE) Facultad de Ciencias BiológicasPontificia Universidad Católica de ChileSantiagoChile

The liver is frequently affected by severe acute respiratory syndrome-coronavirus 2(SARS-CoV-2)*** most common manifestations are mildly elevated alanine aminotransferase and aspartate aminotransferase,with a prevalence of 16-53%among *** with severe coronavirus disease 2019(COVID-19)seem to have higher rates of acute liver dysfunction,and the presence of abnormal liver tests at admission signifies a higher risk of severe disease during *** with chronic liver diseases also have a higher risk of severe disease and mortality(mainly seen in patients with metabolic-associated fatty liver disease).Several pathways of damage have been proposed in the liver involvement of COVID-19 patients;although,the end-cause is most likely *** liver tests have been attributed to the expression of angiotensin-converting enzyme 2 receptors in SARS-CoV-2 *** enzyme is expressed widely in cholangiocytes and less in *** factors attributed to liver damage include drug-induced liver injury,uncontrolled release of proinflammatory molecules(“cytokine storm”),pneumonia-associated hypoxia,and direct damage by the *** steatosis,vascular thrombosis,fibrosis,and inflammatory features(including Kupffer cell hyperplasia)are the most common liver histopathological findings in deceased COVID-19 patients,suggesting important indirect mechanisms of liver *** this translational medicinebased narrative review,we summarize the current data on the possible indirect mechanisms involved in liver damage due to COVID-19,the histopathological findings,and the impact of these mechanisms in patients with chronic liver disease.

关键词： COVID-19 SARS-CoV-2 Liver hepatitis Liver injury Novel coronavirus

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Ni-based catalysts obtained from perovskites oxides for ethanol steam reforming

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燃料化学学报 2018年第11期46卷 1332-1341页

作者： Fabiola Nerina Agüero Jose antonio Alonso maria Teresa Fernández-Díaz luis Eduardo Cadus Instituto de Investigaciones en Tecnología Química(INTEQUI) UNSL-CONICETAlmirante Brown 14555700 San LuisArgentina Instituto de Ciencia de materiales de madrid Consejo Superior de Investigaciones CientíficasCantoblanco28049 MadridSpain Institut Laue-Langevin B.P.156F-38042 Grenoble Cedex 9France

Perovskites as host structures of cations were used in order to generate in situ active and stable catalysts for ethanol steam reforming. For this purpose,La_(1-x)mg_xAl_(1-y)Ni_yO_3(x = 0.1; y = 0,0.1,0.2,0.3) perovskites were synthetized by the citrate *** segregation is evident for a substitution level higher than 0. 2. The segregation of Ni as NiO generated species interacts with different metal-support after the reduction step. The y = 0.1 catalyst presents the highest H_2 yield value about 85% during reaction time,with low mean values of CH_4 and CO selectivities of 3.4% and 11%,respectively and a low carbon formation. The better performance of y = 0.1 catalyst could be attributed to the minor proportion of segregated phases,thus a controlled expulsion of Ni is successfully reached.

关键词： perovskites catalyst design ethanol steam reforming

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Reliability Inference for multicomponent Stress–strength model under Pareto Distribution

Reliability Inference for Multicomponent Stress–strength Mo...

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作者： luis antonio Vasquez Ellis 浙江工商大学

学位级别：硕士

This study considers the reliability of a multi componentstress-strength model involving one stress and multiple strengths from a series *** the maximum likelihood and Bayesian methods are presented to obtain the estimates of the reliability when the stress and strength variables follow the general Pareto distribution with the common shape parameter and different scale ***,the model with unequal shape parameters is *** likelihoodmethod,theexistenceanduniqueness of maximum likelihood estimators are shown,while for the Bayesian method,the necessary and sufficient conditions of the propriety of the posterior distribution based on the Jeffreys prior are *** both methods we need to calculate the Jacobian matrix with derivatives of the distribution functions and the determinant of this *** proving all these things,*** methodsisevaluatedby monte Carlo simulation by running thousands of samples runs with set parameters to estimate these *** running the simulation,the results show that the Bayesian method outperforms the maximum likelihood method,especially for bigger sample *** all these simulations are ran then we use a real dataset proposed by other authors and is analyzed for illustration.

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Changes in Cinnamic Acid Derivatives Associated with the Habituation of maize Cells to Dichlobenil

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molecular Plant 2011年第5期4卷 869-878页

作者： Hugo melida Jesus Alvarez Jose luis Acebes antonio Encina Stephen C. Fry Area de Fisiologia Vegetal Facultad de CC Biologicas y Ambientales Universidad de Leon E-24071 Leon Spain Edinburgh Cell Wall group Institute of Molecular Plant Sciences School of Biological Sciences University of Edinburgh Daniel Rutherford Building The King＇s Buildings Edinburgh EH9 3JH UK

The habituation of cell cultures to cellulose biosynthesis inhibitors such as dichlobenil （DCB） represents a valu- able tool to improve our knowledge of the mechanisms involved in plant cell wall structural plasticity. maize cell lines habituated to lethal concentrations of DCB were able to grow through the acquisition of a modified cell wall in which cellulose was partially replaced by a more extensive network of arabinoxylans. The aim of this work was to investigate the phenolic metabolism of non-habituated and DCB-habituated maize cell cultures. maize cell cultures were fed [14C]cinnamate and the fate of the radioactivity in different intra-protoplasmic and wall-localized fractions throughout the culture cycle was analyzed by autoradiography and scintillation counting. Non-habituated and habituated cultures did not markedly differ in their ability to uptake exogenous [14C]cinnamic acid. However, interesting differences were found in the radiolabeling of low- and high-mr metabolites. Habituated cultures displayed a higher number and amount of radiola-beled low-mr compounds, which could act as reserves later used for polysaccharide feruloylation. DCB-habituated cultures were highly enriched in esterified [14C]dehydrodiferulates and larger coupling products. In conclusion, an extensive and early cross-linking of hydroxycinnamates was observed in DCB-habituated cultures, probably strengthening their cellulose-deficient walls.

关键词： Cell wall zea mays maize dichlobenil DCB dehydrodiferulate ferulate cinnamic acid.

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Embryo and Endosperm Phytochemicals from Polyembryonic maize Kernels and Their Relationship with Seed germination

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Phyton-International Journal of Experimental Botany 2022年第5期91卷 929-941页

作者： J.David garcía-Ortíz Rebeca gonzález-Centeno maría Alejandra Torres-Tapia J.A.Ascacio-Valdés JoséEspinoza-Velázquez Raúl Rodríguez-Herrera Food Research Department School of ChemistryAutonomous University of CoahuilaSaltillo25280México Plant Breeding Department Universidad Autonoma Agraria Antonio Narro(UAAAN)Saltillo25315México

Because of the growing worldwide demand for maize grain,new alternatives have been sought for breeding of this cereal,e.g.,development of polyembryonic varieties,which agronomic performance could positively impact the grain yield per unit area,and nutritional *** objectives of this study were to(1)determine the phytochemicals present in the embryo and endosperm of grain from maize families with high,low,and null polyembryony frequency,which were planted at different locations,and(2)state the relationship between these compounds and seed *** extracted phytochemicals from corn were identified by *** results showed that the genotype with the highest presence of phytochemicals was the brachytic population with high polyembryony called“BAP”,which also required less water during the germination *** number of phytochemicals in both embryo and endosperm tissues was not related to the sowing location where they came from or the type of *** number of different phytochemicals depended on the grain tissue from where they were *** chemical compounds found in the different maize tissues were related to the development of the plant,either in roots or nibs because these are mainly associated with the lignin synthesis.

关键词： zea mays L HPLC-mS locations kernels phytochemicals

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Dynamics of Droplets of Biological Fluids on Smooth Superhydrophobic Surfaces under Electrostatic Actuation

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Journal of Bionic Engineering 2016年第2期13卷 220-234页

作者： Ana Sofia moita Catarina Laurencia Joana Anastacio Ramos Duarte miguel Franca Prazeres antonio luis Nobre moreira IN+ - Center for Innovation Technology and Policy Research Instituto Superior Tecnico Universidade de Lisboa Av. Rovisco Pais 1049-001 Lisboa Portugal iBB - Institute for Bioengineering and Biosciences Department of Bioengineering Instituto Superior Tecnico Universidade de Lisboa Av. Rovisco Pais 1049-001 Lisboa Portugal

This study describes the dynamic behaviour of droplets of biological liquids on hydrophobic surfaces under electrostatic actuation, to devise sample handling in lab-on-chip diagnostic tools. Bovine Serum Albumin （BSA） is taken as a representative biomolecule, since it is often used in adsorption studies. green Fluorescence Protein （gFP） is also considered, given its natural fluorescence. Several effects such as sample concentration and pH are discussed. The results show negligible effects of proteins concentration in electrowetting, although increased concentrations endorse passive adsorption mechanisms, which alter the local wettability of the substrates precluding droplet motion. Bioinspired surfaces promote the largest spreading diameter, which is beneficial for droplet motion. However, surface roughness promotes energy dissipation limiting the receding droplet motion. Hence, the most effective approach is altering the surface chemistry. The coating is applied to a surface with a mean roughness smaller than 20 nm and does not alter significantly the topography, thus leading to the so-called smooth superhydrophobic surface. This coating also reduces passive proteins adsorption, as confirmed by Confocal microscopy （Cm）, which is beneficial for droplet motion. Evaluating absorption spectra of protein solutions evidences an increase in protein concentration ascribed to droplet evaporation as confirmed by theoretical analysis and time resolved infrared visualization.

关键词： bioinspired surfaces biofluids electrostatic actuation hydrophobicity adsorption evaporation

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gene expression and physiological responses to salinity and water stress of contrasting durum wheat genotypes

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Journal of Integrative Plant Biology 2016年第1期58卷 48-66页

作者： Salima Yousfi antonio J.marquez marco Betti Jose luis Araus maria Dolores Serret Unit of Plant Physiology Department of Plant BiologyFaculty of BiologyUniversity of Barcelona08028Spain Department of Plant Biochemistry and molecular Biology Faculty of ChemistryUniversity of SevilleSevilla 41012Spain

Elucidating the relationships between gene expression and the physiological mechanisms remains a bottleneck in breeding for resistance to salinity and drought. This study related the expression of key target genes with the physiological performance of durum wheat under different combinations of salinity and irrigation. The candidate genes assayed included two encoding for the DREB（dehydration responsive element binding） transcription factors Ta DREB1 A and Ta DREB2 B, another two for the cytosolic and plastidic glutamine synthetase（Ta gS1 and Ta gS2）, and one for the specific Na^＋/H^＋ vacuolar antiporter（Ta NHX1）. Expression of these genes was related to growth and different trait indicators of nitrogen metabolism（nitrogen content, stable nitrogen isotope composition, and glutamine synthetase and nitrate reductase activities）, photosynthetic carbon metabolism（stable carbon isotope composition and different gas exchange traits） and ion accumulation. Significant interaction between genotype and growing conditions occurred for growth, nitrogen content, and the expression of most *** general terms, higher expression of Ta gS1, Ta gS2,Ta DREB2 B, and to a lesser extent of Ta NHX1 were associated with a better genotypic performance in growth, nitrogen, and carbon photosynthetic metabolism under salinity and water stress. However, Ta DREB1 A was increased in expression under stress compared with control conditions, with tolerant genotypes exhibiting lower expression than susceptible ones.

关键词： Durum wheat (Triticum turgidum ssp. durum) geneexpression nitrogen metabolism salinity stable isotope

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