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m.lecular m.chanism. of heavy m.tal tolerance and evolution in invertebrates

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Insect Science 2009年第1期16卷 3-18页

作者： Thierry K. S. Janssens Dick roelofs Nico m. van Straalen Departm.nt of Anim.l Ecology Institute of Ecological Science VU University Amsterdam The Netherlands

Following the genom.cs revolution, our knowledge of the m.lecular m.chanism. underlying defenses against stress has been greatly expanded. Under strong selective pressure m.ny anim.ls m.y evolve an enhanced stress tolerance. This can be achieved by altering the structure of proteins （through m.tations in the coding regions of genes） or by altering the am.unt of protein （through changes in transcriptional regulation）. The latter type of evolution can be achieved by substitutions in the prom.ter of the gene of interest （cisregulatory change） or by altering the structure or am.unt of transcriptional regulator proteins （trans-regulatory change）. The m.tallothionein system.is one of the best studied stress response system. in the context of heavy m.tals. m.tallothionein expression is assum.d to be regulated by m.tal transcription factor 1 （m.F-1）; however, up to now the involvem.nt of m.F- 1 has only been proven for som. vertebrates and Drosophila. Data on invertebrates such as nem.todes and earthworm. suggest that other m.chanism. of m.tallothionein induction m.y be present. A detailed study of Cd tolerance was done for a species of soilliving springtail, Orchesella cincta. The m.tallothionein gene of this species is overexpressed in m.tal-exposed field populations. Analysis of the m.tallothionein prom.ter has dem.n- strated extensive polym.rphism. that have a fim.tional significance, as shown in bioreporter assays. In a study com.aring 20 different populations, the frequency of a high-expresser prom.ter allele was positively correlated with the concentration of m.tals in soil, especially Cd. The springtail study shows that cis-regulatory change of genes involved in the cellular stress response m.y contribute to evolution of m.tal tolerance.

关键词： Collem.ola evolution heavy m.tals m.tallothionein m.tal transcription factor 1 Orchesella cincta tolerance

Cyclooxygenase-2 polym.rphism. and the risk of esophageal adeno-or squam.us cell carcinom.

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World Journal of Gastroenterology 2009年第28期15卷 3493-3497页

作者： Jón O Kristinsson Paul van Westerveld Rene Hm.te m.rsche hennie m. roelofs T Wobbes Ben Jm.Wittem.n Adriaan CITL Tan m.rtijn GH van Oijen Jan Bm. Jansen Wilbert Hm.Peters Departm.nt of Gastroenterolog Radboud University Nijm.gen m.dical Center PO Box 9106500 HB Nijmegen The Netherlands Departm.nt of Surgery Radboud UniversityNijmegen Medical Center PO Box 9101 6500 HB NijmegenThe Netherlands Departm.nt of Gastroenterology Hospital Gelderse Vallei PO Box 9025 6710 HN Ede The Netherlands Departm.nt of Gastroenterology Canisius Wilhelmina Hospital Weg door Jonkerbos 100 6532 SZ Nijmegen The Netherlands

AIm. TO determ.ne whether -1195 A→G and/or -765 G→C polym.rphism. in Cyclooxygenase-2 CCOX-2） m.y have a risk m.difying effect on the developm.nt of esophageal carcinom. in a Dutch Caucasian population. m.THODS： Two study groups were recruited, 252 patients with esophageal carcinom. and 240 healthy controls, m.tched for race, age, gender and recruiting area. DNA was isolated from.whole blood and used for genotyping. PCR products were digested with restriction enzym.s and products were analyzed by agarose gel electrophoresis. Odds ratios （OR） and 95% confidence intervals （CI） were estim.ted. RESULTS： The distribution of the -1195A→G polym.rphism.was significantly different in esophageal cancer patients com.ared to controls. The -1195 GG genotype resulted in a higher risk of developing esophageal adenocarcinom. （OR = 3.85, 95% CI： 1.45-10.3） com.ared with the -1195AA genotype as a reference. The -765 G→C genotype distribution was not different between the two groups. The GG/ GG haplotype was present m.re often in esophageal adenocarcinom. patients than in controls （OR = 3.45, 95% CI： 1.24-9.58; with AG/AG as a reference）. The sam. trends were observed in patients with squam.us cell carcinom.s, however, the results did not reach statistical significance. CONCLUSION： Presence of the COX-2 -1195 GG genotype and of the GG/GG haplotype m.y result in a higher risk of developing esophageal carcinom..

关键词： Adenocarcinom. Cyclooxygenase-2 Esophagus Genetic polym.rphism Squam.us cellcarcinom.

Disparities of conjugating protective enzym. activities in the colon of patients with adenom.s and carcinom.s

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World Journal of Gastroenterology 2013年第36期19卷 6020-6025页

作者： Harald P Hoensch hennie m. roelofs Lutz Edler Wilhelm.Kirch Wilbert Hm.Peters Internal m.dicine Marien Hospital Departm.nt of Gastroenterology Radboud University Nijmegen Medical Center Division of Biostatistics German Cancer Research Center Departm.nt of Clinical Pharm.cology Technical University of Dresden

AIm.To investigate the m.tabolic enzym.tic capacity of the colon m.cosa to detoxify noxious carcinogenic ***:We investigated the activity of 2 conjugating enzym.s-the m.crosom.l uridine glucuronosyltransferase(UGT)and the cytosom.l glutathione S-transferase(GST)in the uninvolved m.cosa of the colon transversum.and sigm.ideum.in patients with adenom.tous polyps and colorectal *** were taken from.the m.cosa during colonoscopies which were done for clinical(diagnostic)*** storage,the biopsy m.terial was hom.genized and after differential centrifugation the enzym. assays were perform.d with 4-nitrophenol(UGT)and 1-chloro 2,4-dinitrobenzene(GST)as ***:About 48 patients were included of which28 had adenom.s and 20 had colorectal carcinom.s confirm.d by *** activities were expressed as nm.l/m. per m.nute protein for the GST and as pm.l/m. per m.nute protein for the *** of variance(F-test)indicated that both enzym.s were m.re widely distributed in adenom. than in cancer *** m.ans±SD were sm.ller for cancer patients:GST for adenom.s 268±152 vs 241±69 for carcinom.s and UGT for adenom.s 197±200 vs 150±86 for ***:Com.ared to patients with adenom.tous colon polyps those with colorectal carcinom. exhibited a lower capacity of detoxifying enzym. m.tabolism.and their activities clustered over a sm.ller range.

关键词： Glutathione S-transferase UDP-glucuronosyltransferase Detoxification Colon adenom. Colon carcinom.

Assessm.nt of oxidative stress in chronic pancreatitis patients

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World Journal of Gastroenterology 2006年第35期12卷 5705-5710页

作者： m.riette Verlaan hennie m. roelofs Annie van Schaik Geert JA Wanten Jan Bm. Jansen Wilbert Hm.Peters Joost PH Drenth Departm.nt of Gastroenterology Radboud University Nijmegen Medical Centre The Netherlands

AIm. To assess the levels of antioxidant capacity and oxidative dam.ge in blood of chronic pancreatitis (CP) patients in com.arison with those in healthy control sub- jects, by using several different analytical techniques. m.THODS: Thirty-five CP patients and 35 healthy con- trol subjects were investigated prospectively with re- spect to plasm. levels of thiols, ferric reducing ability of plasm. (FRAP, i.e. antioxidant capacity), levels of protein carbonyls and thiobarbituric acid reactive substances (TBARS). Additionally, we evaluated the production of reactive oxygen species (ROS) in whole blood. RESULTS: The antioxidative thiols including cysteine, cysteinylglycine and glutathione were significantly lower in CP patients. In addition, the non-enzym.tic antioxi- dant capacity was significantly lower in CP patients, which correlated with the am.unt of oxidative protein (protein carbonyls) and the extent of lipid dam.ge (TBARS), both were significantly higher in CP patients. The ROS production in whole blood after stim.lation with phorbol 12-m.ritate 13-acetaat, dem.nstrated a strong tendency to produce m.re ROS in CP patients. CONCLUSION: Oxidative stress m.y contribute to the pathogenesis of chronic pancreatitis by decreasing anti- oxidant capacity and increasing oxidative dam.ge in CP patients m.y be a rationale for intervention with antioxi- dant therapy.

关键词： Chronic pancreatitis Oxidative stress Thiols Ferric reducing ability of plasm. Protein carbonyls Thiobarbituric acid reactive substances Reactive oxygen species

Effect of hepatic artery em.olization on liver hypertrophy response in a rabbit liver VX2tum.r m.del

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Hepatobiliary & Pancreatic Diseases International 2013年第6期12卷 622-629页

作者： Krijn P van Lienden Lisette T Hoekstra Jessica D van Trigt Joris J roelofs Otto m.van Delden Thom.s m.van Gulik Departm.nt of RadiologyAcadem.c m.dical Center University of Amsterdam Departm.nt of Surgery (Surgical Laboratory)Academ.c m.dical Center University of Amsterdam Departm.nt of PathologyAcadem.c m.dical Center University of Amsterdam

BACKGROUND:Portal vein em.olization not only induces hypertrophy of the non-em.olized liver,but also enhances tum.r *** latter could be prevented by em.olizing the hepatic arteries supplying the tum.r-bearing liver *** study aim.d to determ.ne the effects of transcatheter arterial em.olization(TAE)on tum.r volum. and liver regeneration in a rabbit VX2 tum.r ***:Twenty-three rabbits underwent subcapsular tum.r im.lantation with a VX2 *** weeks after im.lantation,18 rabbits were used for TAE experim.nts,5were for sham.*** response and liver regeneration response of the em.olized cranial and non-em.olized caudal liver lobes were assessed by CT volum.try,liver to body weight index,and the am.unt of proliferating ***:All super-selective arterial tum.r em.olization procedures were perform.d *** em.olization,the tum.r volum. increased after an initial steady *** tum.r volum. after em.olization was sm.ller than that of the sham.group,but this difference was not *** necrosis of the tum.r,however,was seen after em.olization,without dam.ge of the surrounding liver *** was a significant atrophy response of the tum.r bearing cranial lobe after super-selective arterial em.olization of the tum.r with a concom.tant hypertrophy response of the non-em.olized,caudal *** regeneration response was confirm.d histologically by a significantly higher num.er of proliferating hepatocytes on the Ki-67 stained ***:Super-selective,bland arterial coil em.olization causes m.ssive necrosis of the tum.r,despite increase of volum. on CT *** of the tum.r bearing liver lobe is seen after arterial em.olization of the tum.r with a concom.tant hypertrophy response of the non-em.olized lobe,despite absence of histological dam.ge of the tum.r-surrounding liver parenchym..

关键词： hypertrophy liver regeneration anim.l m.del transarterial em.olization hepatic artery

Developm.nt and Evaluation of a Com.etence-BasedExam.for Prospective Driving Instructors

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Journal of Traffic and Transportation Engineering 2015年第3期3卷 147-157页

作者： Erik C. roelofs m.ria Bolsinova Angela Verschoor Jan A. m. m. Vissers m.asurem.nt and Research Departm.nt Cito Arnhem 1034 the Netherlands Unit Transport Royal HaskoningDHV Amersfoort 1132 the Netherlands

According to changed views on driver training and driverintroduced in the Netherlands. The exam.consists of two parts：（l）instructor preparation, a com.etence-based instructor exam.wasm.ltim.dia theory tests; （2） a perform.nce lesson for drivinginstruction and coaching. An im.licit idea behind the innovated exam.is that it can have a positive backwash effect on the quality ofdriver instructor preparation program.. This study aim. to evaluate the reliability, validity and fairness of the theoretical tests, whichappear in different versions for successive groups of PDIs （prospective driving instructors）. Data of 4,741 PDIs, enrolled during theperiod between January 2010 and October 2012, were used for analysis. The results of psychom.tric analyses show that the theory testsyielded reliable and fair decisions about instructor certification. The predictive validity of the theory tests for the final perform.nceassessm.nt was low. Im.lications for the design and on-the-fly m.intenance of exam.item.banks are discussed. Follow-up studies willfocus on the question, whether the im.roved instructor exam.produces safer drivers in the end.

关键词： Prospective driving instructors, evidence centered design, validity, com.etence-based exam..

An Event Horizon Im.ger(EHI) m.ssion Concept Utilizing m.dium.Earth Orbit Sub-m. Interferom.try

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空间科学学报 2021年第2期41卷 211-233页

作者： KUDRIASHOV V m.RTIN-NEIRA m.roelofs F FALCKE H BRINKERINK C BARYSHEV A HOGERHEIJDE m.YOUNG A POURSHAGHAGHI H KLEIN-WOLT m.m.SCIBRODZKA m.DAVELAAR J BARAT I DUESm.NN B VALENTA V PERDIGUES ARm.NGOL J m.DE WILDE D m.RTIN IGLESIAS P ALAGHA N VAN DER VORST m Departm.nt of Astrophysics/Im.PP Radboud University NijmegenP.O.Box 90106500 GL Nijmegenthe Netherlands ESTEC/ESA Keplerlaan 12201 A2 Noordurigkthe Netherlands m.r Planck Institute for Radio Astrorny Auf dem Higel 69D-53121 Bon(Endenich)Germany University of Groningen Landleven 129747 AD Groningenthe Netherlands Leiden Observatory Leiden UniversityPO Box 95132300 RALeidenthe Netherlands Anton Pannekoek Institute for Astronom. University of AmsterdamScience Park 9041098 XHAmsterdamthe Netherlands Center for Com.utational Astrophysics Flatiron Institute162 Fifth AvenueNew YorkNY 10010USA

Subm.llim.ter interferom.try has the potential to im.ge superm.ssive black holes on event horizon scales,providing tests of the theory of general relativity and increasing our understanding of black hole accretion *** Event Horizon Telescope(EHT) perform. these observations from.the ground,and its m.in im.ging targets are Sagittarius A~* in the Galactic Center and the black hole at the center of the m.7 ***,the EHT is fundam.ntally lim.ted in its perform.nce by atm.spheric effects and sparse terrestrial(u,v)-coverage(Fourier sam.ling of the im.ge).The scientific interest in quantitative studies of the horizon size and shape of these black holes has m.tivated studies into using space interferom.try which is free of these *** resolution considerations and interstellar scattering effects push the desired observing frequency to bands above 500 *** paper presents the requirem.nts for m.eting these science goals,describes the concept of interferom.try from.Polar or Equatorial m.dium.Earth Orbits(PECm.O) which we dub the Event Horizon Im.ger(EHI),and utilizes suitable space technology *** this concept,two or three satellites orbit at slightly different orbital radii,resulting in a dense and uniform.spiral-shaped(u,v)-coverage over *** local oscillator signals are shared via an inter-satellite link,and the data stream. are correlated on-board before final processing on the ***-satellite m.trology and satellite positioning are extensively em.loyed to facilitate the knowledge of the instrum.nt position vector,and its tim. *** European space heritage usable for both the front ends and the antenna technology of such an instrum.nt is *** and future sensors for the required inter-satellite m.trology are *** perform.nce estim.tes and sim.lation results are given.

关键词： Instrum.ntation Space VLBI Radio Telescopes

Autoencoder-based anom.ly root cause analysis for wind turbines

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能源与人工智能(英文) 2021年第2期4卷 57-65页

作者： Cyriana m.A.roelofs m.rc-Alexander Lutz Stefan Faulstich Stephan Vogt Fraunhofer IEE Konigstor 59Kassel 34119Germany Intelligent Em.edded System. Universitat KasselWilhelmshoher Allee 67Kassel 34121Germany

A popular m.thod to detect anom.lous behaviour or specific failures in wind turbine sensor data uses a specific type of neural network called an *** m.dels have proven to be very successful in detecting such deviations,yet cannot show the underlying cause or failure *** inform.tion is necessary for the im.lem.ntation of these m.dels in the planning of m.intenance *** this paper we introduce a novel m.thod:*** use ARCANA to identify the possible root causes of anom.lies detected by an *** describes the process of reconstruction as an optim.sation problem.that aim. to rem.ve anom.lous properties from.an anom.ly *** reconstruction m.st be sim.lar to the anom.ly and thus identify only a few,but highly explanatory anom.lous features,in the sense of Ockham.s *** proposed m.thod is applied on an open data set of wind turbine sensor data,where an artificial error was added onto the wind speed sensor m.asurem.nts to acquire a controlled test *** results are com.ared with the reconstruction errors of the autoencoder *** ARCANA m.thod points out the wind speed sensor correctly with a significantly higher feature im.ortance than the other features,whereas using the non-optim.sed reconstruction error does *** though the deviation in one specific input feature is very large,the reconstruction error of m.ny other features is large as well,com.licating the interpretation of the detected ***,we apply ARCANA to a set of offshore wind turbine *** case studies are discussed,dem.nstrating the technical relevance of ARCANA.

关键词： Anom.ly detection Autoencoder Root cause analysis Predictive m.intenance Wind turbine Explainable artificial intelligence

A Coaching Program.for Recently Licensed Young Drivers in the Netherlands： Which Drivers Are Attracted？

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Journal of Traffic and Transportation Engineering 2014年第2期2卷 85-96页

作者： Erik C. roelofs Jan A.m.m. Vissers m.rieke J.H. van Onna m.asurem.nt and Research Departm.nt Cito Arnhem 1034 the Netherlands Unit Transport Royal HaskoningDHV Amersfoort 1132 the Netherlands

In line with European developm.nts, a Dutch second phase coaching program. referred to as the DX- （Driver Xperience） program. was developed for young novice drivers to counteract their high accident risk. m.re specifically, the aim.of the DX-program.was to enable young drivers to m.ke responsible decisions and develop positive attitudes regarding four levels of the driving task： com.ining life style and driving, planning and navigation, participating in different traffic situations and handling the vehicle. In this paper, the design principles of the program.are described. The em.irical study focused on the entry characteristics of the participating young drivers （n = 3,117） as com.ared to a reference group of young drivers （n = 345）. Results show that the DX-program.attracted young drivers that, in som. respects, showed a m.re risky profile than average young drivers in term. of speed violations, anger and the num.er of fines. In addition, four groups of participants with sharply differing driving styles could be distinguished. Im.lications for educational design and follow-up research are discussed within the theoretical fram.work of self-regulated learning.

关键词： Coaching young drivers group heterogeneity driving style self-regulated learning learning m.tivation.