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Genome-wide Studies Reveal Genetic Risk f.ctors f.r Hepatic f.t Content

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Genomics, Proteomics & Bioinf.rmatics 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 Lif.lines Cohort Study Vincent E.de Meijer Serena Sanna Robin P.f.Dullaart Hans Blokzijl Eleonora A.M.f.sten Jingyuan f. 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 f.tty liver disease(MAf.D)is complex and poorly *** characterization of.the genetic background of.hepatic f.t content would provide insights into disease etiology and causality of.risk *** perf.rmed genome-wide association study(GWAS)on two noninvasive def.nitions of.hepatic f.t content:magnetic resonance imaging proton density f.t f.action(MRI-PDf.)in 16,050 participants and f.tty liver index(f.I)in 388,701 participants f.om the United Kingdom(UK)Biobank(UKBB).Heritability,genetic overlap,and similarity between hepatic f.t content phenotypes were analyzed,and replicated in 10,398 participants f.om the University Medical Center Groningen(UMCG)Genetics Lif.lines Initiative(UGLI).Meta-analysis of.GWASs of.MRI-PDf. in UKBB revealed f.ve statistically signif.cant 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,TM6Sf.,and *** of.f.I in UKBB identif.ed 196 genome-wide signif.cant loci,of.which 49 were replicated in UGLI,with top signals in ZPR1(P=3.35E−13)and f.O(P=2.11E−09).Statistically signif.cant genetic correlation(rg)between MRI-PDf.(UKBB)and f.I(UGLI)GWAS results was f.und(rg=0.5276,P=1.45E−03).Novel MRI-PDf. genetic signals(CREB3L1 and GCM1)were replicated in the f.I *** identif.ed two novel genes f.r MRI-PDf. and 49 replicable loci f.r *** a dif.erence in hepatic f.t content assessment between MRI-PDf. and f.I,a substantial similar genetic architecture was *** is identif.ed as an easy and reliable approach to study hepatic f.t content at the population level.

关键词： Hepatic f.t content MAf.D Genome-wide association study f.tty liver index Magnetic resonance imaging proton density f.t f.action

Bayesian Model Calibration with Interpolating Polynomials based on Adaptively Weighted Leja Node

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Communications in Computational Physics 2020年第1期27卷 33-69页

作者： Laurent van den bos Benjamin Sanderse Wim Bierbooms Gerard van Bussel Centrum Wiskunde&Inf.rmatica P.O.Box 940791090 GBAmsterdamThe Netherlands Delf. University of.Technology P.O.Box 52600 AADelftThe Netherlands

An ef.icient algorithm is proposed f.r Bayesian model calibration,which is commonly used to estimate the model parameters of.non-linear,computationally expensive models using measurement *** approach is based on Bayesian statistics:using a prior distribution and a likelihood,the posterior distribution is obtained through application of.Bayes’*** novel algorithm to accurately determine this posterior requires signif.cantly f.wer discrete model evaluations than traditional Monte Carlo *** key idea is to replace the expensive model by an interpolating surrogate model and to construct the interpolating nodal set maximizing the accuracy of.the *** determine such a nodal set an extension to weighted Leja nodes is introduced,based on a new weighting *** prove that the convergence of.the posterior has the same rate as the convergence of.the *** the convergence of.the posterior is measured in the Kullback–Leibler divergence,the rate *** algorithm and its theoretical properties are verif.ed in three dif.erent test cases:analytical cases that conf.rm the correctness of.the theoretical f.ndings,Burgers’equation to show its applicability in implicit problems,and f.nally the calibration of.the closure parameters of.a turbulence model to show the ef.ectiveness f.r computa-tionally expensive problems.

关键词： Bayesian model calibration interpolation Leja nodes surrogate modeling

Multi-threaded compression of.Earth observation time-series data

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International Journal of.Digital Earth 2017年第12期10卷 1214-1230页

作者： D.Swanepoel f.van den Bergh Remote Sensing Research Unit Meraka InstituteCSIRPretoriaSouth Africa

Earth observation data are typically compressed using general-purpose single-threaded compression algorithms that operate at a f.action of.the bandwidth of.modern storage and processing *** present evidence that recently developed multi-threaded compression codecs of.er substantial benef.ts over widely used single-threaded codecs in terms of.compression ef.iciency when applied to a selection of.moderate resolution imaging spectroradiometer(MODIS)datasets stored in the HDf. *** codecs f.om the LZ77 and Rice f.milies are shown to vary in ef.icacy when applied to dif.erent MODIS data products,highlighting the need f.r compression strategies to be tailored to dif.erent classes of.*** also introduce LPC-Rice,a new multi-threaded codec,that perf.rms particularly well when applied to time-series data.

关键词： Data compression multithreading time-series HDf HDf. MODIS

Quantitative resistance against Bemisia tabaci in Solanum pennellii:Genetics and metabolomics

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Journal of.Integrative Plant Biology 2016年第4期58卷 397-412页

作者： f.oor van den Oever-van den Elsen Alejandro f.Lucatti Sjaak van Heusden Colette Broekgaarden Roland Mumm Marcel Dicke Ben Vosman Wageningen UR Plant Breeding Wageningen University and Research CentreP.O.Box 3866700AJWageningenThe Netherlands Laboratory of.Entomology Wageningen University and Research CentreP.O.Box 166700AAWageningenThe Netherlands Graduate School Experimental Plant Sciences Droevendaalsesteeg 16708 PB WageningenThe Netherlands Plant Research International Business Unit BioscienceWageningen University and Research CentreP.O.Box 166700AA WageningenThe Netherlands

The whitef.y Bemisia tabaci is a serious threat in tomato cultivation worldwide as all varieties grown today are highly susceptible to this devastating herbivorous *** accessions of.the tomato wild relative Solanum pennellii show a high resistance towards B. tabaci. A mapping approach was used to elucidate the genetic background of.whitef.yresistance related traits and associated biochemical traits in this species. Minor quantitative trait loci（QTLs） f.r whitef.y adult survival（AS） and oviposition rate（OR） were identif.ed and some were conf.rmed in an f.BC1 population, where they showed increased percentages of.explained variance（more than 30%）. Bulked segregant analyses on pools of.whitef.yresistant and-susceptible f. plants enabled the identif.cation of.metabolites that correlate either with resistance or susceptibility. Genetic mapping of.these metabolites showed that a large number of.them co-localize with whitef.yresistance QTLs. Some of.these whitef.y-resistance QTLs are hotspots f.r metabolite QTLs. Although a large number of.metabolite QTLs correlated to whitef.y resistance or susceptibility, most of.them are yet unknown compounds and f.rther studies are needed to identif. the metabolic pathways and genes involved. The results indicate a direct genetic correlation between biochemical-based resistance characteristics and reduced whitef.y incidence in S. pennellii.

关键词： Genetic linkage map lif.-history metabolic f.ngerprinting parameters tomato whitef.y

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People Management in Hospitals: Where Doctors and HR Do (Not?) Meet

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Health 2022年第6期14卷 629-649页

作者： Myra van den Goor Tanya Bondarouk Anna bos-Nehles Company f.r Prof.ssional Physician Development Q3 BV Den Bosch The Netherlands f.culty of.Behavioural Management and Social Sciences University of Twente Enschede The Netherlands

Objective: Although HR activities are known to enhance perf.rmance, this seems an of.en overlooked domain amongst physicians. Theref.re, this cross-disciplinary interview study explores how physicians perceive high perf.rmance and what activities they f.nd contributing to such perf.rmance. Methods: Drawing on HR and healthcare literature, we analysed in-depth interviews with 28 physicians and 7 HR prof.ssionals and hospital management representatives, f.llowing the grounded theory approach. Results: Our f.ndings demonstrate physicians perceive high perf.rmance as a balance between quality of.medical care and patient satisf.ction and dedication and collaboration are indicated vital dimensions of.high perf.rmance. Physicians of.ered suggestions regarding activities contributing to high perf.rmance. Conclusion: This cross-disciplinary study recognized dedication and collaboration as crucial elements f.r physicians to perf.rm to the best of.their abilities. These f.ndings suggest that high perf.rmance can only f.ourish when doctors are seen as committed prof.ssionals, with strong humanistic values rather than just as providers of.medical care. The results of.this research f.rthermore indicate that people management is critical, it is recommended that this should be executed through close collaboration of.all those responsible.

关键词： Physician Perf.rmance Humanistic Values People Management HR Practices Healthcare

Assessment of.f.od supplementation and surveillance as techniques to reduce damage caused by black capuchin monkeys Sapajus nigritus to f.rest plantations

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Current Zoology 2014年第5期60卷 581-590页

作者： Sandra bos MIKICH Laboratory of.Ecology (Laborat6rio de Ecologia) Embrapa Florestas Caixa Postal 319 CEP 83411-000 Colombo PR Brazil Black Capuchin Monkey Program (Programa Macaco-prego) National Fund for the Control of Forest Pests (Fundo Nacional de Controle de Pragas Florestais) Dieter Liebsch Environmental Consulting (Dieter Liebsch Consultoria Ambiental) Curitiba PR Brazil dieterliebsch@yahoo.com.br

Black capuchin monkeys Sapajus nigritus are among several mammalian species that damage f.rest plantations, pri- marily plantations of.pine trees （Pinus spp.） in South Brazil. Management practices to reduce these damages include supplemen- tary f.od of.erings and plantation surveillance. To assess the ef.iciency of.these techniques, f.ur treatments were evaluated： f.eding （f. with supplementary bananas and maize）, surveillance （S, in situ, wherein men patrolled the plantations, deterring the monkeys）, f.eding ＋ surveillance （f.） and control （no procedures）（C）. The ef.iciency assessment of.each treatment involved the number of.recorded primate sightings in the treatments with the presence of.guards （S and f.） and a damage inventory of.the outskirts of.the experimental points immediately bef.re and af.er the experiment. These data were complemented by a simulta- neous study of.the availability of.f.uit, the primary item in the diet of.this primate species, in the remnant native f.rest in the study area. Most sightings of.S. nigritus occurred early in the morning, and in general, sightings were inversely proportional to the availability of.native f.uits. This trend was most evident in treatment f., most likely due to the presence of.f.od. Treatments f.and f. exhibited higher percentages of.damage, indicating that these are inef.icient management techniques. Treatment S exhi- bited the lowest damage rate, but at a high cost, making this technique dif.icult to apply over large expanses. The development of.other management techniques, such as environmental enrichment and the use of.deterrents, is recommended to minimize the damage caused by capuchins in f.rest plantations [Current Zoology 60 （5）： 581-590, 2014].

关键词： Cebus Damage control Wildlif. management Pinus f.od provisioning

Immunotherapy with immune checkpoint inhibitors in colorectal cancer:what is the f.ture beyond def.cient mismatch-repair tumours?

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Gastroenterology Report 2020年第1期8卷 11-24,I0001页

作者： Nicolas Huyghe Pamela Baldin Marc van den Eynde Institut de Recherche Clinique et Expe´rimentale(Pole MIRO) UCLouvainBrusselsBelgium Department of.Pathology Cliniques Universitaires St-LucInstitut Roi Albert IIBrusselsBelgium Department of.Medical Oncology Cliniques Universitaires St-LucInstitut Roi Albert IIBrusselsBelgium

f.llowing initial success in melanoma and lung tumours,immune checkpoint inhibitors(ICIs)are now well recognized as a major immunotherapy treatment modality f.r multiple types of.solid *** colorectal cancer(CRC),the small subset that is mismatch-repair-def.cient and microsatellite-instability-high(dMMR/MSI-H)derive benef.t f.om immunotherapy;however,the vast majority of.patients with prof.cient MMR(pMMR)or with microsatellite stable(MSS)CRC do *** and the consensus molecular subtype classif.cations are promising biomarkers in predicting therapeutic ef.icacy in selected *** pMRR/MSS CRC,biomarkers are also needed to understand the molecular mechanisms governing immune reactivity and to predict their relationship to *** continuous development of.such biomarkers would of.er new perspectives and more personalized treatments by targeting oncological options,including ICIs,which modif. the tumour-immune *** this review,we f.cus on CRC and discuss the current status of.ICIs,the role of.biomarkers to predict response to immunotherapy,and the approaches being explored to render pMMR/MSS CRC more immunogenic through the use of.combined therapies.

关键词： colorectal cancer immunotherapy immune checkpoint inhibitors immune response immunoscore

Development of.^(18)f.labeled radiotracers f.r neuroreceptor imaging with positron emission tomography

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Neuroscience Bulletin 2014年第5期30卷 777-811页

作者： Peter Brust Jrg van den Hof. Jrg Steinbach Helmholtz-Zentrum Dresden-Rossendorf Institute of Radiopharmaceutical Cancer ResearchPermoserstrasse 15Leipzig04318Germany

Positron emission tomography （PET） is an in vivo molecular imaging tool which is widely used in nuclear medicine f.r early diagnosis and treatment f.llow-up of.many brain diseases. PET uses biomolecules as probes which are labeled with radionuclides of.short half.lives, synthesized prior to the imaging studies. These probes are called radiotracers. f.uorine-18 is a radionuclide routinely used in the radiolabeling of.neuroreceptor ligands f.r PET because of.its f.vorable half.lif. of.109.8 min. The delivery of.such radiotracers into the brain provides images of.transport, metabolic, and neurotransmission processes on the molecular level. Af.er a short introduction into the principles of.PET, this review mainly f.cuses on the strategy of.radiotracer development bridging f.om basic science to biomedical application. Successf.l radiotracer design as described here provides molecular probes which not only are usef.l f.r imaging of.human brain diseases, but also allow molecular neuroreceptor imaging studies in various small-animal models of.disease, including genetically- engineered animals. f.rthermore, they provide a powerf.l tool f.r in vivo pharmacology during the process of.pre-clinical drug development to identif. new drug targets, to investigate pathophysiology, to discover potential drug candidates, and to evaluate the pharmacokinetics and pharmacodynamics of.drugs in vivo.

关键词： Alzheimer's disease autoradiography blood-brain barrier brain tumor cholinergic system kinetic modeling metabolism molecular imaging neurodegeneration positron emission tomography precursor psychiatric disorder radiotracer sigma receptor

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The inf.uence of.dif.erent exercise intensities on kicking accuracy and velocity in soccer players

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Journal of.Sport and Health Science 2017年第4期6卷 462-467页

作者： Ricardo f.rraz Roland van den Tillar Mario C. Marques Department of.Sports Sciences University of Beira Interior Convento de St Antonio Covilha 6200-001 Portugal Research Center in Sport Sciences Health Sciences and Human Development CIDESD Vila Real 5000-801 Portugal Department of.Teacher Education Nord Trondelag University College Levanger 7600 Norway

Purpose: The aim of.this study was to investigate the inf.uence of.dif.erent exercise intensities induced by a soccer specif.c protocol on kicking perf.rmance in soccer ***: Twelve semi-prof.ssional male soccer players participated in this study and perf.rmed maximal instep kicks bef.re and af.er the implementation of.an exercise protocol to determine the inf.uence of.dif.erent intensities upon kicking ball velocity and the target-hitting ***: Analysis of.variance designs with repeated measures showed that maximal ball velocity was af.ected only af.er the most intense circuit(f.6, 66) = 2.3; p = 0.041; η2= 0.18), while accuracy was not af.ected in the protocol(f.6, 66) = 0.19; p = 0.98; η2= 0.02). Low and moderate intensities did not af.ect accuracy or kicking ball ***: These f.ndings suggest that kicking ball velocity is inf.uenced by high-exercise intensities. Low and moderate exercise intensities do not af.ect the perf.rmance of.the kick, and intensity does not inf.uence accuracy. Otherwise, it is possible that other mechanisms(not only physiological) may inf.uence players during the exercise.

关键词： Exercise intensity f.tigue Kicking soccer Pacing

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