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Integrative phosphoproteomics defines two biologically distinct groups of KMT2A rearranged acute myeloid leukaemia with different drug response phenotypes

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Signal Transduction and Targeted Therapy 2023年第3期8卷 1318-1331页

作者： pedro casado Ana Rio-Machin Juho JMiettinen Findlay Bewicke-copley Kevin Rouault-Pierre Szilvia Krizsan Alun Parsons Vinothini Rajeeve Farideh Miraki-Moud David cTaussig csaba Bödör John Gribben caroline Heckman Jude Fitzgibbon pedro R.cutillas cell Signalling and Proteomics Group Centre for Genomics and Computational BiologyBarts Cancer InstituteQueen Mary University of LondonLondon EC1M6BQUK centre for Genomics and computational Biology Barts Cancer InstituteQueen Mary University of LondonLondon EC1M6BQUK Institute for Molecular Medicine Finland-FIMM HiLIFE-Helsinki Institute of Life ScienceiCAN Digital Precision Cancer Medicine FlagshipUniversity of HelsinkiHelsinkiFinland centre for Haemato-Oncology Barts Cancer InstituteQueen Mary University of LondonLondon EC1M6BQUK HcEMM-SU Molecular Oncohematology Research Group 1st Department of Pathology and Experimental Cancer ResearchSemmelweis University BudapestBudapestHungary cancer Research UK cancer Therapeutics Unit Division of Cancer TherapeuticsThe Institute of Cancer ResearchSuttonUK a The Alan Turing Institute The British Library2QR96 Euston RdLondon NW12DBUK

Acute myeloid leukaemia(AML)patients harbouring certain chromosome abnormalities have particularly adverse *** these patients,targeted therapies have not yet made a significant clinical *** understand the molecular landscape of poor prognosis AML we profiled 74 patients from two different centres(in UK and Finland)at the proteomic,phosphoproteomic and drug response phenotypic *** data were complemented with transcriptomics analysis for 39 *** integration highlighted a phosphoproteomics signature that define two biologically distinct groups of KMT2A rearranged leukaemia,which we term MLLGA and *** presented increased DOT1L phosphorylation,HOXA gene expression,cDK1 activity and phosphorylation of proteins involved in RNA metabolism,replication and DNA damage when compared to MLLGB and no KMT2A rearranged *** was particularly sensitive to 15 compounds including genotoxic drugs and inhibitors of mitotic kinases and inosine-5-monosphosphate dehydrogenase(IMPDH)relative to other ***-risk KMT2A-MLLT3 cases were mainly represented in a third group closer to MLLGA than to *** expression of IMPDH2 and multiple nucleolar proteins was higher in MLLGA and correlated with the response to IMPDH inhibition in KMT2A rearranged leukaemia,suggesting a role of the nucleolar activity in sensitivity to *** summary,our multilayer molecular profiling of AML with poor prognosis and KMT2A-MLLT3 karyotypes identified a phosphoproteomics signature that defines two biologically and phenotypically distinct groups of KMT2A rearranged *** data provide a rationale for the potential development of specific therapies for AML patients characterised by the MLLGA phosphoproteomics signature identified in this study.

关键词： metabolism signature biologically

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In vivo optical quality of posterior-chamber phakic implantable collamer lenses with a central port

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Eye and Vision 2021年第5期8卷 295-302页

作者： Robert Montés-Micó Francisco Pastor-Pascual Enrique Artiaga-Elordi Ramón Ruiz-Mesa pedro Tañá-Rivero Optics and Optometry&Vision Sciences Department University of Valenciac/o Dr Moliner 5046100 ValenciaSpain Oftalvist clinic ValenciaSpain

Background:The aim of this review is to summarize the optical quality results in patients following the implantation of the V4c implantable collamer lens with a central port(IcL,STAAR Surgical Inc.).Main text:A literature search in several databases was carried out to identify those publications,both prospective,retrospective and/or comparative with other refractive surgery procedures,reporting optical outcomes of patients who were implanted with the V4c IcL model.A total of 17 clinical studies published between 2012 and 2021 were included in this review.A detailed analysis of the available data was performed including number of eyes,follow-up and preoperative spherical ***,the review focused on several optical parameters including higher-order aberrations(HOAs),modulation transfer function(MTF)cut-off frequency and Strehl *** review encompassed a total of 817 eyes measured using different optical devices based on Hartmann-Shack,retinal image quality measurement and ray-tracing technologies at different ***:The outcomes found in this review lead us to conclude that the IcL V4c model provides good optical quality,by means of different metrics,when implanted.

关键词： Implantable collamer lens Phakic Optical quality Higher order aberrations Modulation transfer function

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Deadly oasis:Recurrent annihilation of cretaceous desert bryophyte colonies;the role of solar,climate and lithospheric forcing

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Geoscience Frontiers 2021年第1期12卷 1-12页

作者： Juan pedro Rodríguez-Lópeza Eduardo Barrón Daniel Peyrot Gary B.Hughes Department of Geology.Faculty of Science.United Arab Emirates University.50009.Al Ain Abu DhabiUnited Arab Emirates Instituto Geológico y Minero de Espana(IGME) Ríos Rosas 23E-28003MadridSpain School of Earth and Environment University of Western Australia.6101CrawleyWestern AustraliaAustralia centre for Energy Geosciences University of Western Australia.6101CrawleyWestern AustraliaAustralia Physics Department University of CaliforniaSanta BarbaraCA93106USA

Many oases(wet interdunes)are sedimentary systems characterized by high-frequency water-level oscillations,marked changes in salinity and intense biological activity at their *** are considered to be one of the most challenging environments on Earth for ecosystem *** dynamic,depositional settings are usually unfavourable for fossilization and subsequent preservation of vegetal *** paper describes bryophyte(liverwort)assemblages occurring in three successive horizons interpreted to represent(i)recurrent early successional phases of biological soil crust colonization of wet interdune margins or(ii)exceptional preservation of floating or riparian liverworts in oasis pond waters associated with a progressive fall of the interdune water *** record of in situ colonization surfaces characterized by delicate(***-free)three-dimensional structures represents an exceptional type of preservation herein associated with a rapid variation in phreatic interdune water level and the subsequent establishment of anoxic and reducing *** occurrence of exceptionally preserved liverwort colonies coincides with the sedimentary record of,at least,three seismite levels in the *** gathered from the site suggests that the water table of the oasis was controlled by a combination of(i)a positive creation of accommodation space due to subsidence associated with movement on syn-sedimentary extensional faults,and(ii)the rise and fall of the oasis water table controlled by the oscillations of the groundwater system due to orbital changes which appear to drive the variability of the climate *** groundwater levels flooded the oasis soil crusts and lead to the exceptional recurrent preservation of liverwort colonies at the oasis ***,considering the hypothesis of floating or riparian liverworts in the oasis pond waters,the fall in the level of the oasis water table placed the floating liverworts in contact with the

关键词： Oasis cretaceous Liverworts colonies Extensional tectonics Solar cyclicity

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P2X7 receptor blockade decreases inflammation,apoptosis,and enteric neuron loss during clostridioides difficile toxin A-induced ileitis in mice

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World Journal of Gastroenterology 2022年第30期28卷 4075-4088页

作者： Ana A Q A Santos Deiziane V S costa Danielle A Foschetti Antoniella S G Duarte conceicao S Martins pedro M G Soares Patricia castelucci Gerly A c Brito Department of Morphology School of MedicineFederal University of CearaFortaleza 60430-170CearaBrazil Department of Physiology and Pharmacology School of MedicineFederal University of CearáFortaleza 60430-170CearaBrazil Department of Pathology and Legal Medicine School of MedicineFederal University of CearaFortaleza 60430-170CearaBrazil Department of Morphology(UFc) Federal University of CearaFortaleza 60430-170CearaBrazil Department of Anatomy Institute of Biomedical SciencesUniversity of São PauloSao Paulo 05508-270Brazil Department of Morphology Federal University of CearaFortaleza 60140-170CearaBrazil

clostridioides difficile(***)is the most common pathogen causing health care-associated *** TcdA and TcdB have been shown to activate enteric neurons;however,what population of these cells is more profoundly influenced and the mechanism underlying these effects remain *** To characterize a specific population of TcdA-affected myenteric neurons and investigate the role of the P2X7 receptor in TcdA-induced ileal inflammation,cell death,and the changes in the enteric nervous system in *** Swiss mice were used to model TcdA-induced ileitis in ileal loops exposed to TcdA(50μg/Loop)for 4 *** investigate the role of the P2X7 receptor,Brilliant Blue G(50 mg/kg,i.p.),which is a nonspecific P2X7 receptor antagonist,or A438079(0.7μg/mouse,i.p.),which is a competitive P2X7 receptor antagonist,were injected one hour prior to TcdA *** samples were collected to analyze the expression of the P2X7 receptor(by quantitative real-time polymerase chain reaction and immunohistochemistry),the population of myenteric enteric neurons(immunofluorescence),histological damage,intestinal inflammation,cell death(terminal deoxynucleotidyltransferasemediated dUTP-biotin nick end labeling),neuronal loss,and S100B synthesis(immunohistochemistry).RESULTS TcdA upregulated(Pceptor gene in the ileal tissues,increasing the level of this receptor in myenteric neurons compared to that in control *** with the control mice indicated that TcdA promoted(Pc calretinin+(calr)and choline acetyltransferase+neurons and increased the number of nitrergic+and calr+neurons expressing the P2X7 *** of the P2X7 receptor decreased TcdAinduced intestinal damage,cytokine release[interleukin(IL)-1β,IL-6,IL-8,and tumor necrosis factor-α],cell death,enteric neuron loss,and S100B synthesis in the mouse *** Our findings demonstrated that TcdA induced the upregulation of the P

关键词： clostridioides difficile clostridioides difficile toxin A P2X7 receptor Enteric nervous system Enteric neuron Enteric glia

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The aryl hydrocarbon receptor and the gut–brain axis

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cellular & Molecular Immunology 2021年第2期18卷 259-268页

作者： Andreia Barroso João Vitor Mahler pedro Henrique Fonseca-castro Francisco J.Quintana Ann Romney center for Neurologic Diseases Brigham and Women’s HospitalHarvard Medical SchoolBostonMAUSA Faculdade de Medicina FMUSP Universidade de São PauloSão PauloSPBrazil Broad Institute of MIT and Harvard CambridgeMAUSA

The aryl hydrocarbon receptor(AHR)is a ligand-activated transcription factor initially identified as the receptor for *** half a century after its discovery,AHR is now recognized as a receptor for multiple physiological ligands,with important roles in health and *** this review,we discuss the role of AHR in the gut–brain axis and its potential value as a therapeutic target for immune-mediated diseases.

关键词： Aryl hydrocarbon receptor Autoimmune diseases Infectious diseases cancer

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Insights into induction of the immune response by the hepatitis B vaccine

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World Journal of Gastroenterology 2022年第31期28卷 4249-4262页

作者： Federico Alejandro Di Lello Alfredo pedro Martínez Diego Martín Flichman Microbiology Universidad de Buenos Aires.Facultad de Farmacia y Bioquímica.Instituto de Investigaciones en Bacteriología y Virología MolecularBuenos Aires C1113AADArgentina consejo Nacional de Investigaciones científicas y Técnicas Buenos Aires C1425FQBArgentina Virology Section Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno“CEMIC”Buenos Aires C1431FWOArgentina Microbiology Universidad de Buenos AiresInstituto de Investigaciones Biomédicas en Retrovirus y Síndrome de Inmunodeficiencia AdquiridaBuenos Aires C1121ABGArgentina

After more than four decades of hepatitis B virus(HBV)vaccine implementation,its safety and efficacy in preventing HBV infection have been proven and several milestones have been *** countries have included HBV immunization schedules in their health policies and progress has been made regarding universalization of the first HBV vaccine dose at *** of these actions have significantly contributed to reducing both the incidence of HBV infection and its related ***,there are still many drawbacks to *** main concerns are the deficient coverage rate of the dose at birth and the large adult population that has not been reached timely by universal ***,the current most widely used second-generation vaccines do not induce protective immunity in 5%to 10%of the population,particularly in people over 40-years-old,obese(body mass index>25 kg/m2),heavy smokers,and patients undergoing dialysis or infection with human immunodeficiency *** developed and approved novel vaccine formulations using more potent adjuvants or multiple antigens have shown better performance,particularly in difficult *** advances re-launch the expectations of achieving the World Health Organization’s objective of completing hepatitis control by 2030.

关键词： Hepatitis B virus Vaccine Immune response Antibodies Neutralizing

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具有温度梯度的电流体动力学传导的数值研究

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Acta Mechanica Sinica 2023年第11期39卷 15-25页

作者：杜中林 pedro A.Vazquez 吴健 School of Energy Science and Engineering Harbin Institute of TechnologyHarbin 150001China Heilongjiang Key Laboratory of Micro-and Nano-scale Fluid Flow and Hea Transfer Harbin 150001China Departamento de Fisica Aplicada Ⅱ SUniversidad de SeillaCamino de los Descubrimientos s/nSevilla 41092Spain

本文模拟研究了温度梯度对电传导现象的流动特性的影响,通过有量纲模拟研究了温度对介电液体物性及介电力的影响.为了更好地辨别不同力的影响,本文考虑了具有温度梯度的二维非对称平行电极配置,研究了介电力对电传导机制的流动模式和强... 详细信息

本文模拟研究了温度梯度对电传导现象的流动特性的影响,通过有量纲模拟研究了温度对介电液体物性及介电力的影响.为了更好地辨别不同力的影响,本文考虑了具有温度梯度的二维非对称平行电极配置,研究了介电力对电传导机制的流动模式和强度的影响.为此,我们通过增大施加的电场强度和温度梯度来改变作用在流场上的介电力.在此过程中,我们同样讨论了介电力方向对流场的影响.结果表明,与流场中单独存在库仑力的情况相比,介电力的存在显着改变了系统的流动模式和强度随着施加的电场强度和温度梯度的增大,介电力对电传导机制的流动特性的影响增强.

关键词：电流体动力学温度梯度电场强度流动模式流动特性电传导库仑力平行电极

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Put Yourself in My Shoes: Perspectives of Adolescents about What Makes an Obesity Intervention Effective

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Health 2015年第14期7卷 1833-1840页

作者： Ana Prioste Helena Fonseca pedro Sousa pedro Gaspar Rita Francisco Maria do céu Machado Researcher at PTDc/DTP-PIc/0769/2012 Project Funded by Fundacao para a Ciência e Tecnologia Lisboa Portugal Department of Paediatrics Hospital de Santa Maria Lisboa Portugal Faculty of Medicine University of Lisbon Lisbon Portugal Instituto Politécnico de Leiria Leiria Portugal Faculdade de Psicologia Universidade de Lisboa Lisboa Portugal

Purpose: This study aims to investigate the adolescents’ perspectives about 1) the changing process promoted by a weight management program;2) the factors which may act as facilitators and barriers to obesity management;3) the strategies that should be included in order to design a successful weight management program. Methods: Data were collected by in-depth interviews and focus group discussions with 16 overweight adolescents, aged 12 - 18 years. Thematic analysis was used for analysing the data. Results: Findings suggest that attributions (internal and external), functions (barriers and facilitators) and perceptual changes (lifestyle and body and mind changes) play distinct roles in the changing process. Interactions recognized as high quality ones, acquisition of new knowledge and competencies and encouragement throughout the process, were identified as facilitators. Negative patterns of interaction, collection of anthropometric data and internal resistances, were identified as barriers. The relevance of developing systemic interventions including family and peers, and the use of Information and communication Technologies were highlighted. conclusion: This study aims to contribute for a deeper understanding of the factors and processes behind adherence to weight management. Implications for the design of future more effective strategies and implementation of appropriate interventions are discussed.

关键词： Adolescence Overweight Weight Management Adherence

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Engineering bionic T cells: signal 1, signal 2, signal 3, reprogramming and the removal of inhibitory mechanisms

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cellular & Molecular Immunology 2020年第6期17卷 576-586页

作者： Iñaki Etxeberria Irene Olivera Elixabet Bolaños Asunta cirella Álvaro Teijeira pedro Berraondo Ignacio Melero Program of Immunology and Immunotherapy Center for Applied Medical Research(CIMA)PamplonaSpain Navarra Institute for Health Research(IDISNA) PamplonaSpain centro de Investigación Biomédica en Red de cáncer(cIBERONc) MadridSpain Department of Immunology and Immunotherapy Clínica Universidad de NavarraPamplonaSpain

Gene engineering and combinatorial approaches with other cancer immunotherapy agents may confer capabilities enabling full tumor rejection by adoptive T cell therapy(AcT).The provision of proper costimulatory receptor activity and cytokine stimuli,along with the repression of inhibitory mechanisms,will conceivably make the most of these treatment *** this sense,T cells can be genetically manipulated to become refractory to suppressive mechanisms and exhaustion,last longer and differentiate into memory T cells while endowed with the ability to traffic to malignant *** antitumor effects can be dramatically augmented with permanent or transient gene transfer maneuvers to express or delete/repress genes.A combination of such interventions seeks the creation of the ultimate bionic T cell,perfected to seek and destroy cancer cells upon systemic or local intratumor delivery.

关键词： Adoptive cell therapy T cell engineering cancer immunotherapy

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Searching for ductile superconducting Heusler X_(2)YZ compounds

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npj computational Materials 2023年第1期9卷 919-927页

作者： Noah Hoffmann Tiago F.T.cerqueira pedro Borlido Antonio Sanna Jonathan Schmidt Miguel A.L.Marques Institut für Physik Martin-Luther-Universität Halle-WittenbergD-06099 HalleGermany cFisUc Department of PhysicsUniversity of CoimbraRua Larga 3004-516 CoimbraPortugal Max-Planck-Institut für Mikrostrukturphysik Weinberg 2D-06120 HalleGermany

Heusler compounds attract a great deal of attention from researchers thanks to a wealth of interesting properties,among which is *** we perform an extensive study of the superconducting and elastic properties of the cubic(full-)Heusler family using a mixture of ab initio methods,as well as interpretable and predictive machine-learning *** analyzing the statistical distributions of these properties and comparing them to anti-perovskites,we recognize universal behaviors that should be common to all conventional superconductors while others turn out to be specific to the material *** total,we discover a total of eight hypothetical materials with critical temperatures above 10 K to be compared with the current record of T_(c)=4.7 K in this ***,we expect most of these materials to be highly ductile,making them potential candidates for the manufacture of wires and tapes for superconducting magnets.

关键词： ductile compounds superconducting

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