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Dermatofibrosarcoma protuberans: from translocation to targeted therapy

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Cancer Biology & Medicine 2015年第4期12卷 375-384页

作者： Jonathan Noujaim Khin Thway Cyril Fisher robin l.jones Sarcoma Unit Royal Marsden NHS Foundation Trust

Dermatofibrosarcoma protuberans(DFSP), the most common dermal sarcoma, is a low-grade, slow growing fibroblastic malignant neoplasm that most frequently affects middle aged adults and is characterized by a high local recurrence rate and a low propensity for metastasis. Wide surgical resection or Mohs micrographic surgery(MMS) are the preferred approaches for localized disease, while radiation therapy is warranted for inoperable disease or for cases with positive margins where re-excision is not possible. DFSP is generally regarded as refractory to conventional chemotherapy. Treatment options for systemic disease were limited until the discovery of a unique translocation, t(17;22)(q22;q13)(COl1A1;PDGFB) found in a majority of cases. In recent years, imatinib, a PDGFβR, ABl and KIT inhibitor, has revolutionized systemic therapy in DFSP. In this review, we summarize the epidemiological, clinical, histological and genetic characteristics of DFSP and update the readers on its current management.

关键词： Dermatofibrosarcoma protuberans(DFSP) imatinib Mohs micrographic surgery(MMS) translocation targeted therapy

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Pazopanib in advanced soft tissue sarcomas

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Signal Transduction and Targeted Therapy 2019年第1期4卷 538-547页

作者： Alex T.J.lee robin l.jones Paul H.Huang Division of Molecular Pathology The Institute of Cancer ResearchLondonUK Sarcoma Unit The Royal Marsden NHS Foundation TrustLondonUK Division of Clinical Studies Institute of Cancer ResearchLondonUK

Pazopanib is the first and only tyrosine kinase inhibitor currently approved for the treatment of multiple histological subtypes of soft tissue sarcoma(STS).Initially developed as a small molecule inhibitor of vascular endothelial growth factor receptors,preclinical work indicates that pazopanib exerts an anticancer effect through the inhibition of both angiogenic and oncogenic signaling *** the establishment of optimal dosing and safety profiles in early phase studies and approval for the treatment of advanced renal cell carcinoma,pazopanib was investigated in STS.A landmark phase III randomized study demonstrated improved progression-free survival with pazopanib compared to that with placebo in pretreated patients with STS of various *** efficacy of pazopanib in specific STS subtypes has been further described in real-world-based case series in both mixed and subtype-specific STS *** present,there are no clinically validated predictive biomarkers for use in selecting patients with advanced STS for pazopanib therapy,limiting the clinical effectiveness and cost-effectiveness of the *** this review,we summarize the preclinical and clinical data for pazopanib,outline the evidence base for its effect in STS and explore reported studies that have investigated putative biomarkers.

关键词： sarcoma clinical approval

Functional mechanism study of the allelochemical myrigalone A identifies a group of ultrapotent inhibitors of ethylene biosynthesis in plants

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Plant Communications 2024年第6期5卷 246-262页

作者： George Heslop-Harrison Kazumi Nakabayashi Ana Espinosa-Ruiz Francesca Robertson Robert Baines Christopher R.l.Thompson Katrin Hermann David Alabadí Gerhard leubner-Metzger robin S.B.Williams Centre for Biomedical Sciences Department of Biological SciencesRoyal Holloway University of LondonEgham TW200EXUK Centre for Plant Molecular Sciences Department of Biological SciencesRoyal Holloway University of LondonEgham TW200EXUK Instituto de Biología Molecular y Celular de Plantas(CSIC-UPV) 46022 ValenciaSpain Centre for life’s Origins and Evolution Department of GeneticsEvolution and EnvironmentUniversity College LondonLondonUK Syngenta Crop Protection AGSteinSwitzerland

Allelochemicals represent a class of natural products released by plants as root,leaf,and fruit exudates that interfere with the growth and survival of neighboring *** how allelochemicals function to regulate plant responses may provide valuable new approaches to better control plant *** such allelochemical,Myrigalone A(MyA)produced by Myrica gale,inhibits seed germination and seedling growth through an unknown ***,we investigate MyA using the tractable modelDictyostelium discoideum and reveal that its activity depends on the conserved homolog of the plant ethylenesynthesis protein 1-aminocyclopropane-1-carboxylic acid oxidase(ACO).Furthermore,in silico modeling predicts the direct binding of MyA to ACO within the catalytic *** ***,ablation of ACO mimics the MyA-dependent developmental delay,which is partially restored by exogenous ethylene,and MyA reduces ethylene *** Arabidopsis thaliana,MyA treatment delays seed germination,and this effect is rescued by exogenous *** also mimics the effect of established ACO inhibitors on root and hypocotyl extension,blocks ethylenedependent root hair production,and reduces ethylene ***,in silico binding analyses identify a rangeof highlypotentethylene inhibitorsthatblock ethylene-dependent responseand reduce ethyleneproduction in ***,we demonstrate a molecular mechanism by which the allelochemical MyA reduces ethylene biosynthesis and identify a range of ultrapotent inhibitors of ethylene-regulated responses.

关键词： 1-aminocyclopropane-1-carboxylic acid ACC ACC oxidase ACO allelochemicals ethylene synthesis inhibitors structure-activity relationship

A study on wildfire impacts on greenhouse gas emissions and regional air quality in South of Orléans,France

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Journal of Environmental Sciences 2024年第1期135卷 521-533页

作者： Chaoyang Xue Gisèle Krysztofiak Yangang Ren Min Cai Patrick Mercier Frédéric le Fur Corinne robin Benoit Grosselin Véronique Daele Max RMcGillen Yujing Mu Valéry Catoire Abdelwahid Mellouki laboratoire de Physique et Chimie de l’Environnement et de l’Espace(lPC2E) CNRS–UniversitéOrléans–CNES(UMR 7328)Orléans Cedex 245071France Institut de Combustion AérothermiqueRéactivitéEnvironnement(ICARE)CNRSOrléans Cedex 245071France Research Centre for Eco-Environmental Sciences Chinese Academy of SciencesBeijing 100085China lig’Air-Association de surveillance de la qualitéde l’air en région Centre-Val de loire Saint-Cyr-en-Val 45590France Mohammed V University RabatMorocco

Wildfire events are increasing globally which may be partly associated with climate change,resulting in significant adverse impacts on local,regional air quality and global *** September 2020,a small wildfire(burned area:36.3 ha)event occurred in Souesmes(loiret-Cher,Sologne,France),and its plume spread out over 200 km on the following day as observed by the MODIS *** on measurements at a suburban site(~50 km northwest of the fire location)in Orléans and backward trajectory analysis,young wildfire plumes were *** increases in gaseous pollutants(CO,CH_(4),N_(2)O,VOCs,etc.)and particles(including black carbon)were found within the wildfire plumes,leading to a reduced air *** factors,defined as EF(X)=ΔX/ΔCO(where,X represents the target species),of various trace gases and black carbon within the young wildfire plumes were determined accordingly and compared with previous *** in the ambient ions(such as ammonium,sulfate,nitrate,chloride,and nitrite in the particle-and gasphase)and aerosol properties(e.g.,aerosol water content,aerosol p H)were also quantified and ***,we estimated the total carbon and climate-related species(e.g.,CO_(2),CH_(4),N_(2)O,and BC)emissions and compared them with fire emission *** biomass burning emission inventories have uncertainties in estimating small fire burned areas and *** instance,we found that the Global Fire Assimilation System(GFAS)may underestimate emissions(e.g.,CO)of this small wildfire while other inventories(GFED and FINN)showed significant *** that it is the first time to record wildfire plumes in this region,related atmospheric implications are presented and discussed.

关键词： Wildfire Air quality Emission factor Emission inventory VOlTAIRE supersite

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Properties and Characterization of Two Clays Raw Material from Mountain District (West of Côte d’Ivoire) for Use in low-Carbon Cements

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Advances in Materials Physics and Chemistry 2024年第8期14卷 137-145页

作者： Wedjers Max robin Manouan Bi Irié Hervé Gouré Doubi lébé Prisca Marie-Sandrine Kouakou Atta Kouamé Brice Koffi Alfred Niamien Kouamé Namory Méité UFR Sciences et Technologies Universit de Man Man Cte dIvoire UFR Sciences Biologiques Universit Peleforo GON COULIBALY Korhogo Cte dIvoire laboratoire de constitution et de raction de la matire Universit Felix Houphout-Boigny Abidan Cte dIvoire

This work was devoted to the study of the physico-chemical properties of two clay minerals from the Mountain District (West Côte d'Ivoire) referenced ME1 and ME2. These samples were characterized by the experimental techniques, such as X-ray diffraction (XRD), Infrared spectroscopy (IR), Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-AES), Differential Thermal Analysis and Thermogravimetry (DTA-TG), Brunauer, Emett and Teller method (BET), laser particle size analysis and Scanning Electron Microscope (SEM). The main results of these analyses reveal that the two clay samples mainly contain quartz (52.91% for ME1 and 51.72% for ME2), kaolinite (36.60% for ME1 and 41.6% for ME2) and associated phases, namely goethite and hematite (13.47% for ME1 and 11.00% for ME2). The specific surface values obtained for samples ME1 and ME2 are 34.78 m2/g and 29.18 m2/g respectively. The results obtained show that the samples studied belong to the kaolinite family. After calcination, they could have good pozzolanic activity and therefore be used in the manufacture of low-carbon cements.

关键词： Quartz Kaolinite Mountain District low-Carbon Cements

Molecular basis of inherited calcium channelopathies:role of mutations in pore-forming subunits

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Acta Pharmacologica Sinica 2006年第7期27卷 799-812页

作者： lynn MCKEOWN Philip robin Owen T jones Faculty of life Sciences the University of ManchesterManchesterUK

The pore-forming alpha subunits of voltage-gated calcium channels contain theessential biophysical machinery that underlies calcium influx in response to *** combination with requisite auxiliary subunits,these pore sub-units form calcium channel complexes that are pivotal to the physiology andpharmacology of diverse cells ranging from sperm to *** surprisingly,mutations in the pore subunits generate diverse pathologies,termedchannelopathies,that range from failures in excitation-contraction coupling tonight *** the last decade,major insights into the mechanisms ofpathogenesis have been derived from animals showing spontaneous or *** parallel,there has been considerable growth in our understandingof the workings of voltage-gated ion channels from a structure-function,regula-tion and cell biology *** we document our current understandingof the mutations underlying channelopathies involving the voltage-gated calciumchannel alpha subunits in humans and other species.

关键词： calcium channels channelopathies mutation

Genome-wide Studies Reveal Genetic Risk Factors for Hepatic Fat Content

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Genomics, Proteomics & Bioinformatics 2024年第2期22卷 57-68页

作者： Yanni li Eline H.van den Berg Alexander Kurilshikov Dasha V.Zhernakova Ranko Gacesa Shixian Hu Esteban A.lopera-Maya Alexandra Zhernakova lifelines Cohort Study Vincent E.de Meijer Serena Sanna robin P.F.Dullaart Hans Blokzijl Eleonora A.M.Festen Jingyuan Fu Rinse K.Weersma Department of Gastroenterology and Hepatology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Genetics University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300052China laboratory of Genomic Diversity Center for Computer TechnologiesITMO UniversitySaint Petersburg 199034Russia Institute of Precision Medicine the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Department of Surgery Section of Hepatobiliary Surgery and Liver TransplantationUniversity of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Endocrinology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Pediatrics University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands 不详

Genetic susceptibility to metabolic associated fatty liver disease(MAFlD)is complex and poorly *** characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk *** performed genome-wide association study(GWAS)on two noninvasive definitions of hepatic fat content:magnetic resonance imaging proton density fat fraction(MRI-PDFF)in 16,050 participants and fatty liver index(FlI)in 388,701 participants from the United Kingdom(UK)Biobank(UKBB).Heritability,genetic overlap,and similarity between hepatic fat content phenotypes were analyzed,and replicated in 10,398 participants from the University Medical Center Groningen(UMCG)Genetics lifelines Initiative(UGlI).Meta-analysis of GWASs of MRI-PDFF in UKBB revealed five statistically significant loci,including two novel genomic loci harboring CREB3l1(rs72910057-T,P=5.40E−09)and GCM1(rs1491489378-T,P=3.16E−09),respectively,as well as three previously reported loci:PNPlA3,TM6SF2,and *** of FlI in UKBB identified 196 genome-wide significant loci,of which 49 were replicated in UGlI,with top signals in ZPR1(P=3.35E−13)and FTO(P=2.11E−09).Statistically significant genetic correlation(rg)between MRI-PDFF(UKBB)and FlI(UGlI)GWAS results was found(rg=0.5276,P=1.45E−03).Novel MRI-PDFF genetic signals(CREB3l1 and GCM1)were replicated in the FlI *** identified two novel genes for MRI-PDFF and 49 replicable loci for *** a difference in hepatic fat content assessment between MRI-PDFF and FlI,a substantial similar genetic architecture was *** is identified as an easy and reliable approach to study hepatic fat content at the population level.

关键词： Hepatic fat content MAFlD Genome-wide association study Fatty liver index Magnetic resonance imaging proton density fat fraction

Changing face of hepatic encephalopathy:Role of inflammation and oxidative stress

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World Journal of Gastroenterology 2010年第27期16卷 3347-3357页

作者： Amit S Seyan robin D Hughes Debbie l Shawcross Institute of liver Studies King's College London School of Medicine at King's College HospitalKing's College Hospital

The face of hepatic encephalopathy(HE) is *** review explores how this neurocognitive disorder,which is associated with both acute and chronic liver injury,has grown to become a dynamic syndrome that spans a spectrum of neuropsychological impairment,from normal performance to *** central role of ammonia in the pathogenesis of HE remains ***,over the past 10 years,the HE community has begun to characterise the key roles of inflammation,infection,and oxidative/nitrosative stress in modulating the pathophysiological effects of ammonia on the *** review explores the current thoughts and evidence base in this area and discusses the potential role of existing and novel therapies that might abrogate the oxidative and nitrosative stresses inflicted on the brain in patients with,or at risk of developing,HE.

关键词： Hepatic encephalopathy Ammonia Inflammation Oxidative stress Astrocyte

Gaming Narratives as Frameworks for Writing Self-assessments

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Journalism and Mass Communication 2013年第9期3卷 585-594页

作者： robin Craft-jones Eastern Michigan University Ypsilanti USA

The paper addresses the disconnected students experience between evaluating their own writing and traditional evaluation methods, despite effective discussion and analysis in the classroom, especially, wide when students＇ reading skills are limited. The paper considers the application of flipping students＇ intense interest and intimate comprehension of video gaming into a lens for evaluating their writing. The sophisticated storylines in some literacy-laden video games rivet students＇ attention in higher order applications while the intricate plots and characters mirror those literary elements taught in print media. Garner comprehension is demandingly complex; transferring literary elements from the game storyline to their writing provides the comprehension carry-over for effective self-evaluation. They can ＂see＂ as a metaphor, those parallel concepts from screen to print, from playing strengths to reading and writing, for them, literary qualities become more transparent, and thus more accessible.

关键词： literacy-rich gaming narratives self-assessment additional revision lens