Heterogeneous reactive systems modeling and correct-by-construction deployment
以大肠杆菌为异源表达复杂的聚酮类化合物生物合成抗菌肽yersiniabactin

A PPLIED AND E NVIRONMENTAL M ICROBIOLOGY,Nov.2003,p.6698–6702Vol.69,No.11 0099-2240/03/$08.00ϩ0DOI:10.1128/AEM.69.11.6698–6702.2003Copyright©2003,American Society for Microbiology.All Rights Reserved.Biosynthesis of Yersiniabactin,a Complex Polyketide-Nonribosomal Peptide,Using Escherichia coli as a Heterologous HostBlaine A.Pfeifer,1Clay C.C.Wang,1Christopher T.Walsh,2and Chaitan Khosla3,4* Chemical Engineering,1Chemistry,3and Biochemistry,4Stanford University,Stanford,California94305,and Department of Biological Chemistry and Molecular Pharmacology,Harvard Medical School,Boston,Massachusetts021152Received20June2003/Accepted18August2003The medicinal value associated with complex polyketide and nonribosomal peptide natural products hasprompted biosynthetic schemes dependent upon heterologous microbial hosts.Here we report the successfulbiosynthesis of yersiniabactin(Ybt),a model polyketide-nonribosomal peptide hybrid natural product,usingEscherichia coli as a heterologous host.After introducing the biochemical pathway for Ybt into E.coli,biosynthesis was initially monitored qualitatively by mass spectrometry.Next,production of Ybt was quantifiedin a high-cell-density fermentation environment with titers reaching67؎21(mean؎standard deviation)mg/liter and a volumetric productivity of1.1؎0.3mg/liter-h.This success has implications for basic andapplied studies on Ybt biosynthesis and also,more generally,for future production of polyketide,nonribosomalpeptide,and mixed polyketide-nonribosomal peptide natural products using E.coli.Polyketides and nonribosomal peptides represent two natu-ral product classes with tremendous therapeutic value(1). Erythromycin(a polyketide antibiotic),vancomycin(a nonri-bosomal peptide antibiotic),and epothilone(a mixed poly-ketide-nonribosomal peptide antitumor agent)represent just a few of these important natural compounds.Harnessing this medicinal relevance,however,is often limited by the rudimen-tary knowledge or poor growth and culturability profiles asso-ciated with the original microbial hosts.In addition,the com-plex structure of these compounds limits efficient synthetic production and leaves microbial fermentation as the only economical route to these plex nonribosomal peptides and polyketides derive from complex or modular en-zymatic systems that show the potential for controlled manip-ulation,given the appropriate cellular host(7).To this end,an initiative to transfer the genetic and biochemical pathways responsible for these natural products from their original mi-crobial hosts to heterologous(and often more amenable)hosts has been implemented(12).This transfer would then offer the best of both worlds:an ideal(or significantly better)and po-tentially universal heterologous host for the controlled produc-tion of therapeutic natural products.However,this simple con-cept faces significant challenges posed by the nature of the complex natural products being produced.To generalize,the heterologous host must generate active enzymatic complexes (either a polyketide synthase[PKS]or nonribosomal peptide synthetase[NRPS])and the substrates that these complexes use for polyketide or nonribosomal peptide biosynthesis.The individual gene size and overall gene number for most modular PKS or NRPS systems pose problems for successful and coor-dinated gene expression(a problem compounded by the need for posttranslational modification of PKS and NRPS via phos-phopantetheinylation).In addition,the individual PKS or NRPS will need a pool of intracellular substrates to biosynthe-size the respective natural product;PKS systems require small acyl coenzyme A substrates,while NRPS complexes use both proteinogenic and nonproteinogenic amino acids.These sub-strates may or may not be native to the heterologous host. Recently,the use of Escherichia coli for the heterologous pro-duction of complex polyketide natural products has been de-scribed(11).E.coli offers many advantages as a heterologous host,and the successful production of a complex polyketide opens future biosynthetic potential for other polyketide prod-ucts with this“user-friendly”organism.There also exists the potential to use this heterologous host to generate other com-plex natural products such as nonribosomal peptides or mixed polyketide-nonribosomal peptides.A candidate system to test the heterologous potential of E. coli further is that for yersiniabactin(Ybt),a siderophore nat-urally produced by Yersinia pestis(the causative agent for bu-bonic plague)during times of iron starvation(9).Ybt is bio-synthesized intracellularly by the modular Ybt synthetase composed of four primary enzymes that were recently used to reconstitute Ybt production in vitro(8)(Fig.1).Initially,YbtE adenylates a salicylate unit for addition to the second biosyn-thesis enzyme,HMWP2.HMWP2consists of two multidomain NRPS modules;as thefirst module accepts the activated sa-licylate unit through an aryl carrier protein,an adenylation domain attaches two cysteine units through thioester bonds to thefirst and second peptidyl carrier proteins.HMWP2then catalyzes the successive addition and cyclization of each cys-teine unit as the growing Ybt chain is then passed to HMWP1. HMWP1contains both a polyketide and nonribosomal peptide module.The ketosynthase domain initially accepts the partial Ybt chain from HMWP2.The PKS portion of HMWP1then catalyzes the addition of a malonate unit(preloaded onto the acyl carrier protein through the acyltransferase domain),and the resultant enzyme-tethered product is reduced(through an NADPH-dependent ketoreductase domain)and methylated (through thefirst methyltransferase domain using S-adenosyl-methionine as a substrate).The HMWP1NRPS module then catalyzes the addition,cyclization,and methylation of afinal*Corresponding author.Mailing address:Department of Chemical Engineering,Stanford University,Stanford,CA94305-5025.Phone and fax:(650)723-6538.E-mail:ck@.6698cysteine unit (presumably loaded through the A domain of HMWP2)before the final thioesterase domain catalyzes the release of Ybt from HMWP1.YbtU acts as a reductase,re-ducing the second thiazoline ring of the growing enzyme-teth-ered product during biosynthesis.YbtT (not depicted in Fig.1)represents an auxiliary enzyme thought responsible for in vivo biosynthetic editing (3).HMWP1,as indicated above,has both an NRPS function (through the addition of a cysteine unit)and a PKS activity (through the incorporation of a malonyl coen-zyme A unit).Hence,Ybt is a mixed polyketide-nonribosomal peptide natural product.In this work,we report the heterologous production of Ybt using E.coli and the implications for this success in both basic and applied studies.Successful production of Ybt further ex-pands the potential to use E.coli as a route to therapeutic polyketide,nonribosomal peptide,and mixed polyketide-non-ribosomal peptide products.For Ybt production,the high cell density titers achieved compare favorably to the industrial pro-duction of other heterologously produced complex natural products.A robust route to Ybt opens the possibility of using this high-af finity molecular ligand to speci fically target or in-hibit pathogenic microbes dependent upon Ybt for survival.MATERIALS AND METHODSStrains and plasmids.E.coli strain K207-3[BL21(DE3)⌬prpRBCD ::T7pro-moter-sfp -T7promoter-prpE panD ::panD25A ygfG ::T7promoter-accA1-T7pro-moter-pccB -T7terminator]was used for all experiments (K207-3is a derivative of BAP1[11]).Plasmids containing the genes for Ybt biosynthesis as well as ybtT were provided on individual expression plasmids as described previously (8).Standard molecular biology protocols were then used to couple these individual genes on multicystronic expression plasmids.pBP198(carbenicillin resistant and derived from pET21c [Novagen,Milwaukee,Wis.])contained (in order)HMWP2and ybtU ,with each gene under the control of its own T7promoter.Likewise,pBP205(kanamycin resistant and derived from pET28a)contained ybtE followed by HMWP1,with each gene under individual T7promoters.An additional plasmid,pBP200,contained ybtT under a T7promoter on a chloram-phenicol-resistant plasmid derived from pGZ119EH (5,10).In vivo gene expression and biosynthesis.Strains K207-3/pBP198/pBP205and K207-3/pBP198/pBP205/pBP200were used for Ybt biosynthesis with all plasmids or plasmid combinations introduced to K207-3via electroporation.All cultures used Luria-Bertani (LB)broth media and contained 100g of carbenicillin/ml,50g of kanamycin/ml,and 34g of chloramphenicol/ml where needed.Cul-tures (typically 5to 10ml)were inoculated 3%(vol/vol)with a previous starter culture,and growth was carried out at 37°C on a rotary shaker (250rpm)to an optical density at 600nm (OD 600)between 0.6and 0.8.Cultures were then cooled at 20°C for 10min.At this point,75M isopropyl--D -thiogalactopyranoside (IPTG)was added together with 1mM salicylate.The culture was then incubated between 12and 30h at either 13or 22°C on a rotary shaker (200rpm).For analysis,samples were centrifuged and 5mM FeCl 3was then added to the resultant supernatant.The supernatant was then either extracted with ethyl acetate or submitted to the Stanford mass spectrometry facility for liquid chro-matography-mass spectrometry (LC-MS)analysis directly.Samples extracted were done so twice with an equal volume of ethyl acetate each time.These samples were dried and also submitted for LC-MS analysis.The gradient used for the LC-MS was a linear method from 2to 98%acetonitrile (balance water)with Ybt-Fe 3ϩobserved by MS at ϳ60%acetonitrile.The fragmentation patternforFIG.1.The Ybt synthetase and its substrates needed to reconstitute Ybt production in E.coli .ArCP,aryl carrier protein;A,adenylation;PCP,peptidyl carrier proteins;Cy,cyclization;KS,ketosynthase;ACP,acyl carrier protein;AT,acyltransferase;KR,NADPH-dependent ketoreductase;MT,methyltransferase;SAM,S -adenosylmethionine;TE,thioesterase.See the text for details on biosynthesis.V OL .69,2003YERSINIABACTIN PRODUCTION IN E.COLI 6699Ybt-Fe3ϩwas also determined and compared to previous reports(2,4).Finally,samples taken experimentally were compared by retention times and fragmen-tation patterns to an authentic sample of Ybt-Fe3ϩ.Negative controls includedK207-3/pBP198,K207-3/pBP205,and K207-3/pBP198/pBP205without added sa-licylate.Cell pellets were sonicated,clarified,and analyzed by sodium dodecylsulfate-polyacrylamide gel electrophoresis to examine the extent of gene expres-sion for both positive and negative controls.High cell density fed-batch fermentation for yersiniabactin purification and quantification.The fermentation procedure derives from a similar effort used for complex polyketide production(10).Briefly,the fermentation medium(termedF1medium)contained KH2PO4at1.5g/liter,K2HPO4at4.34g/liter,(NH4)2SO4at0.4g/liter,MgSO4at150.5mg/liter,glucose at5g/liter,trace metal solution at1.25ml/liter,and vitamin solution at1.25ml/liter.The feed medium contained(NH4)2SO4at110g/liter,MgSO4at3.9g/liter,glucose at430g/liter;trace metalsolution at10ml/liter;vitamin solution at10ml/liter.The trace metals solutionconsisted of FeCl3⅐6H2O at27g/liter,ZnCl2⅐4H2O at2g/liter,CaCl2⅐6H2O at 2g/liter,Na2MoO4⅐2H2O at2g/liter,CuSO4⅐5H2O at1.9g/liter,H3BO3at0.5 g/liter,and concentrated HCl at100ml/liter.The vitamin solution consisted ofriboflavin at0.42g/liter,pantothenic acid at5.4g/liter,niacin at6g/liter,pyri-doxine at1.4g/liter,biotin at0.06g/liter,and folic acid at0.04g/liter.Fed-batch aerated fermentations were conducted by use of an Applikon3LBiobundle system(Applikon Inc.,Foster City,Calif.).A starter culture of K207-3/pBP198/pBP205was grown in1.5ml of LB medium(with100mg of carben-icillin/liter and50mg of kanamycin/liter).After reaching late exponential phaseat37°C and250rpm,the culture was centrifuged and resuspended in50ml of LB(at100-mg of carbenicillin/liter and50mg of kanamycin/liter).The culture grewovernight at30°C and200rpm to stationary phase,was centrifuged,and wasresuspended in20ml of phosphate-buffered saline for inoculation into the3-litervessel containing2liters of F1medium.Growth was conducted at37°C with pHmaintained throughout the experiment at7.1with1M H2SO4and concentratedNH4OH.Aeration was maintained at2.8liters/min with agitation controlled at600to900rpm to maintain dissolved oxygen over50%of air saturation.Thefermentation apparatus including a salt solution[KH2PO4,K2HPO4,and(NH4)2SO4]was autoclaved,whereas the additional components(MgSO4,glucose,tracemetals,and vitamins)werefilter sterilized and added aseptically prior to inocu-lation along with carbenicillin at150mg/liter and kanamycin at75mg/liter.Thefeed medium was alsofilter sterilized.Once the glucose was exhausted from thestarting medium(as indicated by a sudden decrease in the oxygen requirementof the culture),the temperature was reduced to22°C,and IPTG(75M)andsalicylate(0.160g/liter)were added.At that point a peristaltic pump started todeliver0.1ml of the feed medium/min,and samples were typically taken twicedaily thereafter.Initially,afinal fermentation broth was extracted with ethyl acetate(2liters,twice).The extract was dried,resuspended in water and10%acetonitrile,andloaded onto a preparatory high-performance liquid chromatography(HPLC)instrument.A10to100%acetonitrile(balance water)gradient at an8-ml/minflow rate was used to obtain pure Ybt(isolated as an Fe3ϩchelate).Due to Ybtacid sensitivity,no trifluoroacetic acid was used in the HPLC purification pro-cess.The Ybt fractions eluted at75%acetonitrile,and these fractions were pooled,dried,and confirmed to contain Ybt-Fe3ϩby MS.The remaining purified prod-uct was resuspended in water and quantified at385nm by using the knownextinction coefficient(εϭ2884)for Ybt-Fe3ϩ(2).This initial purified batch ofYbt-Fe3ϩwas then used to generate a calibration curve to quantify productionfrom subsequent fermentation time point samples that werefirst clarified beforedirectly loading the fermentation broth onto a preparatory HPLC instrument foranalysis.RESULTSGene expression and biosynthesis.Based upon earlier polyketide biosynthetic schemes,the potential to produce Ybt in E.coli was evaluated.The Ybt synthetase genes were intro-duced into E.coli strain K207-3by using the multicystronic plasmids previously developed(11).Initially,gene expression was analyzed at13or22°C based on previous work using similar postinduction temperatures(8,11).Qualitatively,the large gene products were more abundant at22°C(data not shown),and this postinduction temperature was subsequently used.After successful gene expression was confirmed,in vivo ex-periments commenced for Ybt biosynthesis.The main differ-ence between these and previous experiments was the addition of salicylate upon induction with IPTG.The rest of the Ybt synthetase substrates were presumed to be native to E.coli. Isolation efforts indicated the production of Ybt found to be chelated to Fe3ϩ.This compound was analyzed by LC-MS (Fig.2)with LC retention times nearly identical to those indi-cated in previous reports(2,4)and an authentic Ybt-Fe3ϩstandard.Furthermore,MS and MS fragmentation patterns for the proposed Ybt-Fe3ϩcompound also matched those of previous reports and the authentic standard.Relative compar-isons showed increased Ybt production at22°C compared to that observed at13°C.Production could be eliminated by ex-cluding either of the two expression plasmids needed to recon-stitute the Ybt pathway or by omitting the addition of salicylate to cultures that had been induced for gene expression. Finally,the addition of YbtT,an enzyme thought to edit the biosynthetic production of yersiniabactin,resulted in increased levels of Ybt.Again,based on relative comparisons,the inclu-sion of YbtT increased yersiniabactin productionϳ2.5times over that observed for strains without this enzyme.High-cell-density yersiniabactin production and quantifica-tion.A high-cell-density fermentation was performed to gen-erate Ybt in sufficient quantities needed to readily quantify cellular productivity and overall titers.The fed-batch fermen-tation was initially used as a way to obtain pure Ybt.Upon completion of the fermentation run,Ybt was purified from the fermentation broth by using a combination of organic phase extraction and preparatory HPLC.The purified product was then quantified at385nm by using the known extinction coef-ficient(2).This purified Ybt then served as a standard to quantify thefinal titers for subsequent fermentations.Figure3 shows the results for a typical fermentation run.Final titers of 67Ϯ21mg/liter were reached;the maximum specific produc-tivity of the recombinant E.coli strain was1.2Ϯ0.3mg/liter-h. Both parameters compare well to the biosynthesis of6-deoxy-erythronolide B in the same host(final6-deoxyerythronolide B titer,95.2Ϯ7.7mg/liter;maximum6-deoxyerythronolide B specific productivity,1.1Ϯ0.007mg/liter-h)(10).DISCUSSIONThe development of E.coli-derived Ybt marks an important step forward for heterologously produced complex nonriboso-mal peptide products.Although E.coli has the ability to gen-erate simple nonribosomal peptide products(for example,the native E.coli siderophore enterobactin),Ybt biosynthesis rep-resents an advance due to the complex,modular nature of the Ybt biosynthetic pathway.This biochemical complexity is a hallmark for many important polyketide and nonribosomal peptides(including those examples cited at the beginning of this report),and the present example of heterologous produc-tion through E.coli helps support the notion that this host has the capacity to support production of both natural product classes.In addition,hybrid polyketide-nonribosomal peptide natural products like Ybt should also then be viable options for heterologous production using E.coli.Complex natural product heterologous biosynthesis requires both an active PKS or NRPS and intracellular substrates re-6700PFEIFER ET AL.A PPL.E NVIRON.M ICROBIOL.quired by these enzymes to catalyze their respective products.For Ybt,the yersiniabactin synthetase enzyme complex (con-taining two large,modular proteins in HMWP1and HMWP2)was introduced with multicistronic expression plasmids that facilitated the coordinate expression of all the needed biosyn-thetic genes upon induction with IPTG.Induction by IPTG also called for the expression of a chromosomally located sfp gene needed to activate the biosynthetic enzymesthroughFIG.2.LC-MS analysis of Ybt from K207-3/pBP198/pBP205.The top LC trace shows the Ybt-Fe 3ϩcompound eluting at 16.35min as analyzed by UV at A 210.The bottom trace presents the elution pro file for compounds within the mass range of 535to 536(molecular weight of Ybt-Fe 3ϩ,535).Finally,the MS pattern for the Ybt-Fe 3ϩpeak is presented.FIG.3.Representative fed-batch fermentation for Ybt production.The time courses of OD 600and Ybt titers for strain K207-3/pBP198/pBP205are shown.pBP198(carbenicillin resistant)contained HMWP2and ybtU ,whereas pBP205(kanamycin resistant)held ybtE and HMWP1.Together,pBP198and pBP205expressed the needed genes for complete Ybt reconstitution within the cellular environment of K207-3,a strain genetically engineered to support biosynthesis.V OL .69,2003YERSINIABACTIN PRODUCTION IN E.COLI 6701posttranslational modification.(The sfp gene encodes an Sfp phosphopantetheinyltransferase that was transferred to K207-3from Bacillus subtilus to facilitate complex natural product biosynthesis[11].)Unlike most complex polyketide systems,many of the substrates needed for Ybt biosynthesis are native to E.coli.The exception was a salicylate unit used to initiate biosynthesis.To overcome this,salicylate was simply fed to the media after gene induction.Thus,for biosynthetic substrates that are not native to E.coli or that cannot be metabolically engineered for intracellular production,exoge-nous substrate feeding is yet another option.This study also indicated the enhanced effect that YbtT has on in vivo Ybt production.YbtT is thought to act as an auxil-iary thioesterase enzyme that edits the biosynthetic process, perhaps by removing“misprimed”units that have been incor-rectly attached to the Ybt synthetase complex.In these exper-iments,YbtT increased Ybt productionϳ2.5times.This result supports previous observations that YbtT increases Ybt pro-duction in vivo(3).Interestingly,analogous polyketide systems employing a YbtT analog also show an approximately twofold increase in in vivo polyketide production(10).Finally,the biosynthetic capabilities of this Ybt system were expanded by using the high-cell-density capabilities of E.coli in the context of a fed-batch ing this route pro-duced Ybt at levels comparable to those of heterologous host systems that produce the macrolide6-deoxyerythronolide B(6, 10)and highlights the potential for future heterologous(and therapeutic)polyketide,nonribosomal peptide,or mixed polyketide-nonribosomal peptide product biosynthesis in E. coli.Moreover,given the role of Ybt in establishing virulence for pathogenic microbes,its heterologous production(from a nonpathogenic organism)provides a source of this compound for inhibitor design or targeted drug delivery applications.For example,Ybt analogs,generated through manipulation of the modular Ybt synthetase,or Ybt-drug conjugates might present unique and high-affinity ways to inhibit and target pathogens (such as Yersinia species or other pathogens[13])that have a distinct dependence on Ybt for survival.ACKNOWLEDGMENTSWe thank Sumati Murli at Kosan Biosciences for providing E.coli K207-3.Research in the authors’laboratories was supported by grants from the NIH(GM067937to C.K.and AI42708to C.T.W.).B.A.P.and C.C.C.W.were recipients of an ARCS predoctoral fellowship and an NIH postdoctoral fellowship,respectively.REFERENCES1.Cane,D.E.,and C.T.Walsh.1999.The parallel and convergent universe ofpolyketide synthases and nonribosomal peptide synthetases.Chem.Biol.6:R319–R325.2.Drechsel,H.,H.Stephan,R.Lotz,H.Haag,H.Zahner,K.Hantke,and G.Jung.1995.Structural elucidation of yersiniabactin,a siderophore from highly virulent Yersinia strains.Liebigs Ann.10:1727–1733.3.Geoffroy,V.A.,J.D.Fetherston,and R.D.Perry.2000.Yersinia pestis YbtUand YbtT are involved in synthesis of the siderophore yersiniabactin but have different effects on regulation.Infect.Immun.68:4452–4461.4.Haag,H.,K.Hantke,H.Drechsel,I.Stojiljkovic,G.Jung,and H.Zahner.1993.Purification of yersiniabactin:a siderophore and possible virulence factor of Yersinia enterocolitica.J.Gen.Microbiol.139:2159–2165.5.Lessl,M.,D.Balzer,R.Lurz,V.L.Waters,D.G.Guiney,and nka.1992.Dissection of IncP conjugative plasmid transfer:definition of the trans-fer region Tra2by mobilization of the Tra1region in trans.J.Bacteriol.174:2493–2500.6.Lombo,F.,B.Pfeifer,T.Leaf,S.Ou,Y.S.Kim,D.E.Cane,P.Licari,andC.Khosla.2001.Enhancing the atom economy of polyketide biosyntheticprocesses through metabolic engineering.Biotechnol.Prog.17:612–617. 7.McDaniel,R.,A.Thamchaipenet,C.Gustafsson,H.Fu,M.Betlach,and G.Ashley.1999.Multiple genetic modifications of the erythromycin polyketide synthase to produce a library of novel“unnatural”natural products.Proc.A96:1846–1851.ler,D.A.,L.Luo,N.Hillson,T.A.Keating,and C.T.Walsh.2002.Yersiniabactin synthetase:a four-protein assembly line producing the non-ribosomal peptide/polyketide hybrid siderophore of Yersinia pestis.Chem.Biol.9:333–344.9.Perry,R.D.,P.B.Balbo,H.A.Jones,J.D.Fetherston,and E.DeMoll.1999.Yersiniabactin from Yersinia pestis:biochemical characterization of the siderophore and its role in iron transport and regulation.Microbiology 145:1181–1190.10.Pfeifer,B.,Z.Hu,P.Licari,and C.Khosla.2002.Process and metabolicstrategies for improved production of Escherichia coli-derived6-deoxyeryth-ronolide B.Appl.Environ.Microbiol.68:3287–3292.11.Pfeifer,B.A.,S.J.Admiraal,H.Gramajo,D.E.Cane,and C.Khosla.2001.Biosynthesis of complex polyketides in a metabolically engineered strain ofE.coli.Science291:1790–1792.12.Pfeifer,B.A.,and C.Khosla.2001.Biosynthesis of polyketides in heterolo-gous hosts.Microbiol.Mol.Biol.Rev.65:106–118.13.Welch,R.A.,V.Burland,G.Plunkett III,P.Redford,P.Roesch,D.Rasko,E.L.Buckles,S.R.Liou,A.Boutin,J.Hackett,D.Stroud,G.F.Mayhew,D.J.Rose,S.Zhou,D.C.Schwartz,N.T.Perna,H.L.Mobley,M.S.Donnenberg,and F.R.Blattner.2002.Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli.Proc.A99:17020–17024.6702PFEIFER ET AL.A PPL.E NVIRON.M ICROBIOL.。
橡胶英语翻译

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extrusion共挤吹塑coextrusion blow molding同轴挤塑coaxial extrusion吹胀挤塑blown extrusion挤出吹塑extrusion blow molding挤拉吹塑成型extrusion draw blow molding反应性挤塑reactive extrusion固相挤出solid-phase extrusion发泡expanding foam后发泡post expansion物理发泡physical foam化学发泡chemical foam吹塑blow molding多层吹塑multi-layer blow molding拉伸吹塑成型stretch blow molding滚塑rotational moulding反应注射成型reaction injection molding,RIM 真空成型vacuum forming无压成型zero ressure molding真空烧结vacuum sintering真空袋成型vacuum bag molding热成型thermal forming拉伸热成型stretch thermoforming袋模塑bag molding糊塑paste molding镶铸imbedding冲压成型impact molding触压成型impression molding层压材料laminate泡沫塑料成型foam molding包模成型drape molding充气吹胀inflation橡胶胶乳rubber latex胶乳latex高分子胶体polymer colloid生橡胶raw rubber,crude rubber硬质胶ebonite再生胶reclaimed rubber充油橡胶oil-extended rubber母胶masterbatch交联crosslinking固化cure光固化photo-cure硫化vulcanization后硫化post cure,post vulcanization自硫[化] bin cure自交联self crosslinking ,self curing过硫over cure返硫reversion欠硫under cure动态硫化dynamic vulcanization不均匀硫化heterogeneous vulcanization开始[硫化]效应set-up effect自动硫化self-curing,self-vulcanizing焦烧scorching无压硫化non-pressure cure模压硫化moulding curing常温硫化auto-vulcanization热硫化heat curing蒸汽硫化steam curing微波硫化micro wave curing辐射硫化radiation vulcanization辐射交联radiation crosslinking连续硫化continuous vulcanization无模硫化open vulcanization成纤fiber forming可纺性spinnability纺丝spinning干纺dry spinning湿纺wet spinning干湿法纺丝dry wet spinning干喷湿法纺丝dry jet wet spinning溶液纺丝solution spinning乳液纺丝emulsion spinning乳液闪蒸纺丝法emulsion flash spinning process 喷射纺丝jet spinning喷纺成形spray spinning液晶纺丝liquid crystal spinning熔纺melt spinning共混纺丝blended spinning凝胶纺[丝] gel spinning反应纺丝reaction spinning静电纺丝electrostatic spinning高压纺丝high-pressure spinning复合纺丝conjugate spinning无纺布non-woven fabrics单丝monofilament,monofil复丝multifilament全取向丝fully oriented yarn中空纤维hollow fiber皮芯纤维sheath core fiber共纺cospinning冷拉伸cold drawing,cold stretching单轴拉伸uniaxial drawing,uniaxial elongation双轴拉伸biaxial drawing多轴拉伸multiaxial drawing皮心效应skin and core effect皮层效应skin effect防缩non-shrink熟成ripening垂挂sag定型sizing起球现象pilling effect捻度twist旦denier特tex纱yarn股strand粘合adhesion反应粘合reaction bonding压敏粘合pressure sensitive adhesion底漆primer浸渍impregnation浸渍树脂solvent impregnated resin基体matrix聚合物表面活性剂polymeric surfactant高分子絮凝剂polymeric flocculant预发颗粒pre-expanded bead高分子膜polymeric membraneH-膜H-filmLB膜Langmuir Blodgett film (LB film)半透膜semipermeable membrane反渗透膜Reverse osmosis membrance多孔膜porous membrane各向异性膜anisotropic membrane正离子交换膜cation exchange membrane 负离子交换膜anionic exchange membrane 吸附树脂polymeric adsorbent添加剂additive固化剂curing agent潜固化剂latent curing agent硫化剂vulcanizing agent给硫剂sulfur donor agent,sulfur donor 硫化促进剂vulcanization accelerator硫化活化剂vulcanization activator活化促进剂activating accelerator活化剂activator防焦剂scorch retarder抗硫化返原剂anti-reversion agent塑解剂peptizer偶联剂coupling agent硅烷偶联剂silane coupling agent钛酸酯偶联剂titanate coupling agent铝酸酯偶联剂aluminate coupling agent增强剂reinforcing agent增硬剂hardening agent惰性填料inert filler增塑剂plasticizer辅增塑剂coplasticizer增粘剂tackifier增容剂compatibilizer增塑增容剂plasticizer extender分散剂dispersant agent结构控制剂constitution controller色料colorant荧光增白剂optical bleaching agent抗降解剂antidegradant防老剂anti-aging agent防臭氧剂antiozonant抗龟裂剂anticracking agent抗疲劳剂anti-fatigue agent抗微生物剂biocide防蚀剂anti-corrosion agent光致抗蚀剂photoresist防霉剂antiseptic防腐剂rot resistor防潮剂moisture proof agent除臭剂re-odorant抗氧剂antioxidant热稳定剂heat stabilizer抗静电添加剂antistatic additive抗静电剂antistatic agent紫外线稳定剂ultraviolet stabilizer紫外光吸收剂ultraviolet absorber光稳定剂light stabilizer,photostabilizer 光屏蔽剂light screener发泡剂foaming agent物理发泡剂physical foaming agent化学发泡剂chemical foaming agent脱模剂releasing agent内脱模剂internal releasing agent外脱模剂external releasing agent阻燃剂flame retardant防火剂fire retardant烧蚀剂ablator润滑剂lubricant湿润剂wetting agent隔离剂separant增韧剂toughening agent抗冲改性剂impact modifier消泡剂antifoaming agent减阻剂drag reducer破乳剂demulsifier粘度改进剂viscosity modifier增稠剂thickening agent,thickener阻黏剂abhesive洗脱剂eluant附聚剂agglomerating agent后处理剂after-treating agent催干剂drier防结皮剂anti-skinning agent纺织品整理剂textile finishing agent橡胶专业英文词汇橡胶工艺学-Principles of Rubber Processing 橡胶-Rubber聚合物-Polymer拉伸强度-Tensile strength定伸应力-Modulus撕裂强度-Tear Strength拉断伸长率-Elongation at break永久变形-Permanent Set回弹性-Resilience硬度-Hardness磨耗-Abrasion Resistance抗湿滑性-Wet Skid Resistance生热-Heat build-up门尼粘度-Mooney Viscosity生胶-Gum混炼胶-Compound硫化胶-Vulcanizate硫化体系-Curing System补强填充体系-Reinforcing agents and Filler 防护体系-antiagent增塑体系-Plasticizer塑炼-Plasticate混炼-Mixing or compounding压延-Calendering压出-Extruding硫化-Curing or Crosslinking or Vulcanizing 韩泰-Hancock固特异-Goodyear邓录普-Dunlop生胶-Raw Rubber天然橡胶-NR丁苯橡胶-SBR顺丁橡胶-BR丁腈橡胶-NBR氯丁橡胶-CR乙丙橡胶-EPM,EPDM丁基橡胶-IIR异戊橡胶-IR氟橡胶-FPM硅橡胶-MVQ or Q聚氨酯橡胶-PU丙烯酸酯橡胶-ACM聚硫橡胶-T氯化聚乙烯-CPE氯磺化聚乙烯-CSM聚醚橡胶或氯醇橡胶-CO,ECO环氧化天然橡胶-ENR塑性保持率(抗氧指数)-PRI配合与加工-Compound and Processing粉末橡胶-Powder Rubber胶粉-Crumb,ground rubber再生胶-Reclaimed rubber硫化体系-Curing System硫化仪-valcameter高铁-Gotech硫化曲线-Curing curve诱导期-Induction time焦烧时间-Scorch time焦烧-Scorch工艺正硫化时间(T90)-Optimum curing time理论正硫化时间-Theoretical curing time硫化返原-Curing reversion喷霜-Bloom促进剂-Accelerating agent or Accelerator活性剂-Activating agent or Activator噻唑类-Thiazoles次磺酰胺类-Sulfenamides秋兰姆类-Thiuramsulfides二硫代氨基甲酸盐类-Dithiocarbamates胍类-Guanidines硫脲类-Thioureas醛胺类-Aldehyde amines磺酸盐类-Xanthate普通硫磺硫化体系-Conventional Vulcanization CV 有效硫化体系-Effective Vulcanization EV半有效硫化体系-Semi Effective Vulcanization SEV 平衡硫化体系-Equilibrium cure EC过氧化物硫化体系-Peroxide curing systems金属氧化物硫化体系-Metallic oxides树脂硫化体系-Resin curing system补强与填充体系-Reinforcing and filling system补强-Reinforcing填充-Filling炭黑-Carbon Black炭黑粒径-Particle size of CB炭黑比表面积-Specific surface area of CB氮气吸附-Nitrogen absorption碘吸附-Iodine absorption结构-Structure微观结构-Microstructure炭黑粒子-Carbon Black Particle聚集体-Aggregate附聚体-Agglomerate颗粒-Pellet表面性质-surface activity凝胶-bonded rubber化学吸附-Chemical absorption物理吸附-Physical absorption包容胶-Occluded rubber应力软化效应-Stress softening effect气相法白炭黑-Cas phase silica沉淀法白炭黑-Precipitated silica有机补强剂-organic reinforcer偶联剂-Coupling agent表面活性剂-Surfactant老化-Aging防护-Stabilization塑炼-Mastication or Plastication开炼机-Open roll mill or Open mixer or Rolling mill 密炼机-Internal mixer混炼工艺-Compounding process压延工艺-Calendering process挤出工艺-Extrusion process。
6-酸性树脂催化下液相反应动力学Kinetic of liquid-phase reactions catalyzed by acidic resins

Applied Catalysis A:General197(2000)165–173Kinetic of liquid-phase reactions catalyzed by acidic resins:the formation of peracetic acid for vegetable oil epoxidationR.L.Musante1,R.J.Grau2,M.A.Ba1tanás∗Instituto de Desarrollo Tecnológico para la Industria Qu´ımica(INTEC)Güemes3450,3000Santa Fe,ArgentinaAbstractA heterogeneous kinetic model which takes into account the complete physicochemical interaction of reactive species in a polar liquid phase with an ion-exchange resin acting both as selective sorbent and heterogeneous catalyst has been employed to analyze the peracetic acid synthesis from acetic acid and hydrogen peroxide in an aqueous solution.Model parameters were estimated using uncoupled data from phase equilibria,polymer sorption,chemical equilibrium and reaction kinetics.Activities rather than molar concentrations in the polymer phase and specific(dry weight of catalyst basis)rather than volume-based expressions were found to give the best constitutive equations for the heterogeneous reaction rate.©2000Elsevier Science B.V.All rights reserved.Keywords:Vegetable oil epoxidation;Heterogeneous models;Acidic resins1.IntroductionThe epoxidation of unsaturated triglycerides with percarboxylic acids is a common practice for obtain-ing low cost plasticisers of good performance from natural and renewable sources such as vegetable oils. Cost constrictions dictate the use of inexpensive per-acetic acid(PAA)as the active reagent,while safety concerns demand an in situ preparation of the reagent, to avoid the handling of a pre-formed concentrated peracid.The in situ process involves a heterogeneous system,as epoxidation reaction occurs in the organic phase whereas the formation of PAA takes place ∗Corresponding author.Tel.:+54-342-4559175;fax:+54-342-4550944.E-mail address:tderliq@.ar(M.A.Ba1tan´a s)1Research Assistant of U.N.L.2Professor at U.N.L.and member of CONICET research staff.in an aqueous medium.The latter step is slow and controls the overall reaction rate;then,high conver-sions are generally achieved after several hours of reaction.Traditionally,homogeneous acidic catalysts(e.g. sulfuric acid)have been used to facilitate the forma-tion of peracetic acid by reacting acetic acid(AA) and hydrogen peroxide(HP):CH3COOH(AA)+H2O2(HP)H+←−−→CH3COOOH(PAA)+H2O(W) Hydrogen peroxide(an oxygen source)reacts with acetic acid(an oxygen carrier)in the aqueous phase in the presence of the acidic catalyst(solvated pro-tons)to give peracetic acid(PAA).The latter,in turn, transfers to the organic phase and quickly attacks the double bonds of the unsaturated vegetable oil(VO)to form the oxirane ring in the homogeneous epoxidation0926-860X/00/$–see front matter©2000Elsevier Science B.V.All rights reserved. PII:S0926-860X(99)00547-5166R.L.Musante et al./Applied Catalysis A:General197(2000)165–173 reaction:R1CH=CHR2 (VO)+CH3COOOH (PAA)→R1CHOCHR2(EVO)+CH3COOH (AA)The co-produced AA returns to the aqueous phase to close the sequence and re-start the production cycle. Mass and heat transfer limitations may impose severe process constraints(epoxidations are highly exothermic)or may lead to undesirable side reac-tions.So,numerous workers have studied the epoxi-dation reaction pathway and a qualitative picture of it was agreed upon in the past decades[1–3].The rate-limiting step of the in situ process is the forma-tion of PAA in the aqueous phase.However,quan-titative determination of the kinetic parameters was lacking,and only for two-phase epoxidations using homogeneous mineral acids more rigorous kinetic models had begun to emerge in the recent past[4,5]. As mentioned,secondary(acid-catalyzed)side re-actions do appear.Invariably,they involve an opening of the oxirane ring and,consequently,lower yields of epoxidized vegetable oil[5]:R1CHOCHR2+CH3COOHH+→R1CH(OH)CH(OOCH3)R2R1CHOCHR2+CH3COOOHH+→R1CH(OH)CH(OOOCCH3)R2R1CHOCHR2H +→R1COCH2R2R1CHOCHR2+H2O H+→R1CH(OH)CH(OH)R2R1CHOCHR2+H2O2H+→R1CH(OH)CH(OOH)R2 Heterogeneous catalysts such as functionalized micro-reticular ion-exchange resins(IER)can be advanta-geously used instead,since only the small carboxylic acid molecules can enter into their gel-like structure, while the bulky epoxidized triglyceride molecules cannot.The oxirane ring can thence be protected from the attack of the protons which are confined inside the gel matrix and,as a result,further ring decomposition is prevented.Also,catalyst recovery and/or regeneration is much easier then.Several such strongly acidic sulfonic IER(e.g.Dowex50;Am-berlite IR120,Chempro C20)have been reported to contribute to minimizing oxirane ring opening[6–9]. Three phases are present in the in situ processes cat-alyzed by IER:(1)a polymer phase,whose behavior (notably its swelling properties)is highly dependent on the physicochemical properties of the system,to-gether with(2)an aqueous phase,immiscible with(3) the organic phase.A heterogeneous kinetic model of this three-phase system using IER has not been pre-sented so far.We are presently developing a complete study of the epoxidation process,uncoupling the reac-tion and transport system into sub-systems of increas-ing complexity to allow a better quantification of the relevant process parameters.This piece of work presents the modeling of one of these sub-systems whose understanding is crucial: the kinetics of formation of PAA in the heteroge-neous aqueous phase-polymer(acidic catalyst)phase system.For this,the partition of each component between the two phases,as well as the swelling ra-tio(relative increase of the volume of the resin)are first quantified.Selective sorption/swelling leads to values of the relative compositions in the reaction locus(i.e.the polymer resin)and of the reactants’polymer-phase concentration which are different from those in the liquid phase.Both aspects are taken into account in the modeling.Then,the chemical equilibrium constant and kinetic parameters are esti-mated from the equilibrium and kinetics experimental data,respectively,using operating conditions typical of the industrial stly,the activation en-ergy of the acid-catalyzed reaction is estimated from non-isothermal experimental data.The appropriate-ness of managing the kinetic equations in terms of activities,rather than concentrations,and mass of dry resin,rather than its volume,are discussed.2.Experimental2.1.Activation and conditioning of the ion-exchange resinRohm&Haas Amberlite IR-120microreticular gel-type resin,DVB-styrene matrix,8%cross-linking, d p(dry)=215–775m(54.5%<530m;75.3%<R.L.Musante et al./Applied Catalysis A:General197(2000)165–173167600m;94.8%<670m),functionalized withsulfonic groups,was used throughout this work.AsIER is commercially available in sodium form,hy-drochloric acid(10%w/w)was used to fully activateit in successive ion-exchange steps(7in total),withfurther washing(1:10w/w)using distilled demineral-ized water until complete elimination of the residualstly,glacial acetic acid(purity:>99.7%w/w)was used to replace water inside the ion ex-change resin.The exchange capacity of the resin,as determinedby titration using conventional volumetric tech-niques,was:[H+]o=4.507meq/g(dry basis).The dry polymer density,as measured by pycnometry usingn-heptane[10],was1.437kg/m3.A portion of the dryresin was crushed and sieved;successive washing anddecantation in distilled demineralized water allowedthe removal of undesiredfines adhered to the crushedparticles.Two fractions,<53and>595m,wereused to evaluate the possible impact of mass-transferresistances on the process rate.2.2.Determination of phase equilibrium partitioningof reactants between the aqueous and polymericphasesDifferent dilutions of either acetic acid or hydro-gen peroxide in water(40g)were added to the dryresin(15g).The system was kept at333K with occa-sional stirring until physicochemical equilibrium wasachieved in about4h.The equilibrium compositionof the liquid phase was measured by volumetric tech-niques(see below).A portion of the swollen resin wascentrifuged at2000g for5min to eliminate any resid-ual interstitial liquid[10].The amount of sorbed liq-uid retained by the resin was found by weighting thecentrifuged resin before and after drying in a stove at378K for12h[11].2.3.Reactor and experimental proceduresThe rate of formation of PAA was studied in exper-imental runs conducted in a1000cm3closed cylin-drical Pyrex reactor,furnished with a variable speed(0–1000rpm)mechanical stirrer.The device had fourteflon baffles to eliminate vorticity,an overhead re-flux condenser and a fast-sampling device for collect-ing representative liquid-resin samples of the reacting system.An internal cooling coil(OD:1/4 ;316SS), combined with an external cylindrical heating mantle (400W)linked to a PID temperature controller,en-sured operating within±0.1K.In a typical experiment,glacial AA and pre-activated IER were added to the empty reactor and slowly heated to the reaction temperature under stirring.Si-multaneously,the desired volume of a solution of HP (30%w/w)was also heated to that temperature,under reflux,and then added,at once,to the reactor(zero time of the reaction).Samples were periodically taken and immediatelyfiltered to separate the resin and stop the reaction.Next,aliquots of thefiltrates(1cm3) were diluted in ethanol(100cm3)and refrigerated for further analysis by GLC.2.4.Analytical techniquesThe concentration of AA and HP were measured by volumetric titration,using NaOH(0.l N)and KMnO4 (0.1N),respectively.The contents of PAA acid in the reaction samples was determined by GLC after a previous derivatization with methyl p-tolyl sulphide; n-octadecane was used as internal standard[12].A glass column(500×2mm)packed with3%FFAP on Chromosorb W AW DMCS(80–100mesh)was em-ployed.3.Results and discussion3.1.Intra-and extra-particle mass-transfer resistancesThe absence of intra-particle mass-transfer resis-tances to any significant extent was experimentally corroborated using two widely differing particle sizes of the resin:>595and<53m,under typical reaction conditions of the well-stirred mixture(375rpm).Both runs gave identical results as is shown in Fig.1.Also, the ratio of initial rates was close to unity even though particle diameters differed by more than10-fold. Hence,extra-particle mass-transfer resistances are of no concern either and,thus,the commercial un-crushed lER beads were used to perform the kinetic study.168R.L.Musante et al./Applied Catalysis A:General 197(2000)165–173Fig.1.Influence of particle size of the ion-exchange resin (Amberlite IR-120)on the reaction rate and final concentration of PAA at 333K (reactants molar ratio:H 2O 2/HOAc =1.1/0.5).The full line corresponds to model predictions.3.2.Kinetic modelAs we have pointed out in Section 1,the selec-tive sorption and swelling of the resin can have a strong influence on the observable reaction rate of this two-phase system,even though no change in the se-quence of involved reaction steps (as compared to the homogeneous reaction)is to be expected for a strongly acidic material being the active catalyst.Then,a pseu-dohomogeneous kinetic model such as the following:dd t C PAA =k 1C IER C HP C AA −1K C PAA C W(1)which considers IER merely as a source of protons in the multicomponent liquid mixture would be certainly insufficient.In fact,for the set of experimental runs summarized in Table 2,every attempt we made to get satisfactory data fittings by means of a non-linear re-gression algorithm was unacceptable.So,a new model was developed to include explicitly the presence of the polymer phase.Two approaches can be followed to solve this hur-dle.The first one focuses exclusively on the catalytic reaction pathway at the reaction locus,where two ex-treme situations are recognizable according to whether slightly dissociated sulphonic groups or free solvated protons are the catalytic agents [13–15].The first case applies whenever the resin is imbedded into a slightly polar medium;the classic LHHW formalism can then be applied to model the reaction kinetics [16,17].Here,the inclusion of adsorption parameters is both justifi-able and flexible enough so as to fit up any observ-able changes in catalytic activity due to the presenceof polar components in minor amounts.If the resin operates into a strongly polar solvent such as water,the sulphonic groups are fully dissociated and the free solvated protons catalyze the reaction through ionic mechanisms of protonation.In many such situations,specially if just small amounts of resin are used,a pseudohomogenous model describing the reaction rate in terms of power-law kinetics suffices,as it does in homogeneous catalysis.However,none of these models takes into account the selective sorption and swelling of the resin,which leads to values of the reactants’polymer-phase con-centration and of the relative composition of both reactants and products in the polymer phase (i.e.the reaction locus)that are different from those in the liquid phase.A second approach is then needed,to ex-plicitly differentiate the compositions of the aqueous and polymer phases whenever a significant amount of resin is used as a catalyst.For such purposes,the overall system can be considered as a two-phase sys-tem composed of a highly viscous multicomponent fluid phase containing N +l species (with the swollen polymer as (N +1)th species,)in physicochemical equilibrium with the N -component liquid phase,since the characteristic time for reaching phase-equilibrium conditions between them is usually of the order of a few minutes [18].3.3.Activities of the species in the liquid phase A predictive model is needed to compute the ac-tivity of the four species in the aqueous phase,rather than a correlative one,due to the scant informationR.L.Musante et al./Applied Catalysis A:General197(2000)165–173169 available in the open literature about this reactingsystem.For these components,just a pair of binarydata is available:water–hydrogen peroxide[19]andwater–acetic acid[20].Then,the UNIFAC group con-tribution method[21]is a suitable tool,as it does notinvolve any adjustable parameter.The central con-cept of the method rests on considering any mixtureas a solution of functional groups interacting amongthemselves.Most of the extensions and refinementof the original concept have rested onfinding newprocedures for calculating the molecular interactionparameters between components,which initially camefrom vapor–liquid equilibrium data(UNIFAC VLE).Later,a new set of interaction parameters has beenderived from the liquid–liquid equilibrium data(UNI-FAC LLE)for making predictions related to thesesystems[22].More recently,the dependence of theinteraction parameters with temperature has also beenincluded,in the Modified UNIFAC method[23].We used each of these methods to predict the activ-ities in the aqueous phase.The UNIFAC LLE methodwas found to give the closestfit when a comparison ofmodel predictions with experimental data taken fromthe available vapor–liquid equilibria was made.It wasthen adopted for further use in our calculations.3.4.Activities of the species in the polymer phaseThe activity a P i of the i th species of a multicompo-nent polymeric solution can be evaluated in the frame-work of the extended Flory–Huggins model[25]:ln a P i=1+ln v i−N+1j=1m ij v j+N+1j=1χij v j−N+1j=1j−1k=1m ik v j v kχkj+ηV i53v1/3P−76v P(2)where N is the number of components excluding thepolymer,which is the(N+l)th species;νandνP are thevolume fractions of the i th species and of the polymerin the polymer phase,respectively;m ij is the ratio ofmolar volumes of the i th and j th species(m iP=0); V i is the molar volume of i th species;ηrepresentsthe number of moles of active elastic chains per unitvolume andχij represents the molecular interaction between components i and j.The latter parameters are known to be temperature-dependent[24]. According to Eq.(2),11adjustable parameters would have to be determined for calculating the set of a P i of the four species in the polymer phase:η,and 10molecular interaction parameters,four of them corresponding to interactions between the polymer and the other species(χiP)and six binary interaction parameters among the liquid phase components(χij), sinceχij=χji andχii=0(see Ref.[18]for a full discussion on the subject).The elasticity parameter andfive of the binary interaction parameters were found independently (i.e.uncoupled),from the sorption equilibria of the water–acetic acid and water–hydrogen peroxide bi-nary mixtures in contact with the resin.For this purpose,the activities of each pair of components in the aqueous phase were calculated using the UNIFAC LLE routine,which does not involve any adjustable parameter.Next,as in thermodynamic equilibriuma L i=a P i(3) Eq.(2)was used for each binary mixture,using the Levemberg–Marquardt algorithm,to estimate the cor-responding interaction parameters.Fig.2shows representative sets of tie lines,in adsorbent-free mass coordinates(N=g dry resin/g ad-sorbate),obtained experimentally at333K.These data clearly indicate that water is more strongly sorbed than either acetic acid or hydrogen peroxide,and that the resin swelling is much higher in water than in acetic acid.It is also apparent that the polymer beads can expand even more(albeit slightly)with higher concentration of hydrogen peroxide.Fig.3re-plots the experimental data(tie lines) shown in Fig.2,as molar fractions in the polymer and liquid phases,for the water–acetic acid and water–hydrogen peroxide binary pairs,together with model predictions using the calculated parameters (the latter are included in Table1).The agreement is satisfactory.The experimental determination of the partition of PAA was not made owing to the obvious experi-mental difficulties and hazards involved in handling a highly concentrated peracid.Instead,the heuristic assumption was made that in the polymer phase the analogs—carboxylic acids(acetic and peracetic)—can be assumed to behave as identical molecules,as170R.L.Musante et al./Applied Catalysis A:General 197(2000)165–173Fig.2.Binary sorption and phase partition equilibria on Amberlite IR-120of (a)water–acetic acid and (b)water–hydrogen peroxide binary mixtures,obtained experimentally at 333K,in adsorbent-free mass coordinates (N =g dry resin/gadsorbate).parison of experimental data and model predictions for the water–acetic acid (a)and water–hydrogen (b)binary pairs shown in Fig.2(333K).far as their molecular interactions are concerned,and so χAA −PAA =0.Likewise,an uncoupled estimation of the interaction parameters of the reactive binary pairs,PAA–water and acetic acid–hydrogen peroxide cannot be made,for obvious reasons.Nevertheless,under the previous hypothesis χW −PAA is identical to χW −AA .Lastly,the remaining interaction parameter can be estimated from chemical equilibrium data us-Table 1Estimated values of the interaction parameters of the extended Flory–Huggins model [Eq.(2)],at 333K.χij j i AA HP Water PAA Resin AA 0−0.00880.339000.1592HP −0.00360−1.9670−0.00360.8809Water 0.1039−1.488600.1039−0.6673PAA−0.00880.33900.1592ing asymptotic compositions (i.e.after long enough contact times)of the experimental runs.The proce-dure is described below,in Section 3.5.As is shown in Table 1,the complete set of χij inter-action parameters indicates relatively low interaction between acetic acid,PAA and hydrogen peroxide,and moderate interactions of these with water and of the four liquid components with resin.The value obtained for the elasticity parameter was:η=0.022mol/cm 3,which is about one order of magnitude higher than the theoretical one.However,by imposing progres-sively lower values to this parameter there is worse agreement between model predictions and experimen-tal data results,owing to the tight correlation among the parameters in Eq.(2).This problem has been dis-cussed in a recent work on the kinetics of liquid-phase esterification of acetic acid with ethanol using Am-berlyst 15,where about two orders of magnitude dif-ferences were encountered [18].Despite these shortcomings of presently available phase partition equilibrium models,they allow one to reproduce rather satisfactorily the experimental data and seem sufficient to help in describing the kinetic behavior of these systems under reaction conditions.3.5.Chemical equilibriumBy solving the set of multicomponent sorption equi-librium equations,Eq.(3),together with the mass bal-ances of each of the i th species:n L i +n P i =n 0i +νi ξ(4)R.L.Musante et al./Applied Catalysis A:General 197(2000)165–173171Table 2Initial loading and operating conditions of the batch experimental runs Run Temp (K)AA (moles)HP (moles)Water (moles)Resin mass (g)13331.329 2.73411.4707.44723331.345 3.48015.2058.66733332.783 2.73411.945.22643335.497 2.73411.9474.820533310.945 2.73411.9475.61663330.768 2.73411.94711.99373330.574 2.73411.94721.37583231.329 2.73411.9477.44793431.3292.73411.9477.447and the condition of chemical equilibrium:K =(a P PAAa P W /a P AA a PHP )eq (5)it is possible to jointly estimate the interaction param-eters for the reactive couple acetic acid–hydrogen per-oxide and the equilibrium constant,K .Indeed,owing to a lack of reliable data,it was impossible to estimate K from G 0data,as the standard free energy of the formation of PAA is known within broad uncertainty limits.The calculated value of χHP −AA is given in Table 1.At 333K the equilibrium constant was found to be K =2.18.Values ranging from 0.7to 5,which were found to be dependent both on the initial molar ratio of reac-tants and on the catalyst concentration,calculated from the equilibrium concentrations,have been reported by Rangarajan et al.[5].With our approach,for the broad set of experimental conditions given in Table 2,a good fit of the data could be achieved using a single value of K ,as is shown in Fig.4.The values of K at 323and 343K,obtained exper-imentally,were 1.911and 2.778,respectively.Fig.4.Experimental and calculated concentrations of PAA in liquid phase at equilibrium conditions (333K).3.6.Kinetic equationFrom Eq.(4)it is straightforward to recognize thatin the well-mixed isothermal batch reactor the time rate of change of the observable degree of advance-ment of the reaction (ξ)is sufficient to fully describe the reaction process whenever equilibrium conditions between the bulk liquid and the polymer phase hold.Also,because the catalyzed reaction proceeds only in-side the polymer phase:dd tξ=W P R P (6)where W P indicates mass of dry resin placed in the system (an invariable property)and R P is the specific reaction rate (dry weight basis).Another choice,which is to write Eq.(6)in terms of a volumetric reaction rate,leads to awkward rate ‘constants’,as the volume of the polymer phase continuously changes during the reaction owing to the swelling properties of the resin.In addition,as the system is highly non-ideal,the kinetic equation describing the reaction rate has to be written in terms of activities [26],accounting for the172R.L.Musante et al./Applied Catalysis A:General 197(2000)165–173Fig.5.Concentration of PAA in the liquid phase as a function of time for various values of the initial composition of the reacting mixture:(a)Run 7;(b)Run 6;(c)Run 3.Full lines represent model predictions.chemical equilibrium as well (Eq.(5)).The simplest expression which satisfies these requirements is the following:R P =ka P AA a P HP [1−K −1a P PAA a P W /a P AA a PHP ](7)where k [mol s −1(g dry resin)−1]=k 0[H +]0.Its value was estimated by means of the Marquardt–Levemberg algorithm,solving for Eqs.(2),(3),(5)-(7)and using the experimental data from the runs indicated in Table 2,all of them obtained in the absence of mass-transfer limitations.The previous calculation of the interaction parameters and of the chemical equilibrium constants at each temperature allowed the uncoupled estimation of k .The values of the interaction parameters at 323and 343K were obtained from those at 333K using the well-tested derivation of Flory [24]:χ(T )T =χ(T )T .The estimated values of the pre-exponential factor and activation energy of k are (8.48±l.l6)×10mol s −1(g dry resin)−1and 48.4±0.47kJ mol −1,respectively,for a 95%confidence level.Given that the absence of mass transfer constraints was corroborated,this some-what low E act value,as compared with the onereportedFig.6.Concentration of PAA in the liquid phase as a function of time for various values of the reaction temperature:(a)Run 8;(b)Run 1;(c)Run 9.Full lines represent model predictions.in homogeneous systems,might be due to the steric constraints imposed on the acid-catalyzed bimolecu-lar rds of the reaction [3,4]by the microreticular resin rather than an incomplete degree of solvation [27].Figs.5and 6compare experimental results and model predictions which are fair.Additional fittings were made using empirical kinetic expressions for:(a)the specific reaction rate (dry weight basis)in terms of molar concentrations instead of activities of the re-actants,and (b)the volumetric reaction rate in terms of activities of the components,factorized by the resin volume.In both such cases the new predictions were poorer than the one using the more sound Eq.(7),as the residual sum of squares were 58and 238%higher,respectively.4.ConclusionsA two-phase model has been proposed to describe the catalyzed reaction of the formation of PAA from acetic acid and hydrogen peroxide under a broadR.L.Musante et al./Applied Catalysis A:General197(2000)165–173173range of conditions,using a sulphonated ion-exchange resin acting as both a sorbent and a heterogeneous catalyst.The developed model incorporates relevant aspects with regard to the different affinities of the reactive species toward the liquid and resin phases. The selective partitioning of each component be-tween the two phases and the relative increase of the volume of the resin(i.e.its swelling ratio)with vary-ing composition were corroborated,quantified and taken into account in kinetic modelling.These fea-tures,which have adequate literature support,had not been previously considered for this particular reactive system.A progressive,uncoupled estimation of the model parameters was made using:(a)phase equilib-rium/sorption data of unreactive pairs of components, to obtain the binary interaction parameters;(b)chem-ical equilibrium data,to estimate the thermodynamic equilibrium constant and binary interaction parame-ters of the reactive pairs,and(c)reaction rate data in absence of mass-transfer resistances to estimate the specific kinetic rate constant.Activities rather than molar concentrations and specific(dry weight of cat-alyst based)rather than volume-based reaction rates were used throughout the work.For processing purposes the preferential partition of water inside the catalytic polymer phase(the reaction locus)is inconvenient because,being both a diluent and a reaction product,water lowers the rate of for-mation of PAA from the reversible reaction which is involved.Yet,the use of microreticular ion-exchange resins as heterogeneous catalysts for epoxidizing un-saturated triglycerides is desirable.Protons are then confined inside the polymer phase,which prevents their further attack on the oxirane ring and,so,higher oxirane indexes than those achievable in homogeneous catalytic processes can be realised. AcknowledgementsThanks are given to Leonardo Machaca González and Adolfo Larese for their dedicated experimen-tal work and to Dante L.Chiavassa for his selfless help in handling the computer programs.Thefi-nancial help of Universidad Nacional del Litoral,CONICET,ANPCyT(PD No.019)and JICA is grate-fully acknowledged.References[1]F.Greenspan,R.Gall,JAOCS33(1956)391.[2]H.Wohlers,M.Sack,H.LeVan,Ind.Eng.Chem.50(11)(1958)1685.[3]M.Abraham,R.Benenati,AIChE J.18(4)(1972)807.[4]T.Chou T,J.Chang,mun.41(1986)253.[5]B.Rangarajan,A.Havey,E.Grulke,P.D.Culnan,JAOCS72(10)(1995)1161.[6]R.Gall,F.Greenspan,JAOCS34(1957)161.[7]V.Nagiah,H.Dakshinamurthy,J.Aggarwal,Indian J.Technol.4(1966)280.[8]J.Wisniak,E.Navarrete,Ind.Eng.Chem.Prod.Res.Dev.9(1970)33.[9]B.M.Badran,F.M.El-Mehelmy,N.A.Ghanem,J.Oil ColourChem.Assoc.59(8)(1976)291.[10]B.M.P.Cornel,F.M.H.Sontheimer,Chem.Eng.Sci.41(7)(1986)1791.[11]M.Iborra,C.Fité,J.Tejero,F.Cunill,J.Izquierdo,ReactivePolymers21(1993)65.[12]F.Di Furia,M.Prato,U.Quintily,S.Salvagno,G.Scorrano,Analyst109(1984)985.[13]B.Gates,W.Rodr´ıguez,J.Catal.31(1973)27.[14]J.Tejero,F.Cunill,M.Iborra,J.Mol.Catal.42(1987)257.[15]J.Aragón,J.Vegas,L.Jodra,Ind.Eng.Chem.Res.32(1993)2555.[16]A.AI-Jarallah,A.Siddiqui,K.Lee,Can.J.Chem.Eng.66(1988)802.[17]A.Rehfinger,U.Hoffmann,Chem.Eng.Sci.456(1990)1605.[18]M.Mazzotti,B.Neri,D.Gelosa,A.Kruglov,M.Morbidelli,Ind.Eng.Chem.Res.36(1997)3.[19]G.Scatchard,G.Kavanagh,L.Ticknor,J.Am.Chem.Soc.74(15)(1952)3715.[20]J.Gmehling,U.Onken,Vapor–Liquid Equilibria DataCollection V ol I,Part I,DECHEMA,Frankfurt,1977. [21]A.Fredenslund,R.Jones,J.Prausnitz,AIChE J.21(6)(1975)1086.[22]T.Magnussen,P.Rasmussen, A.Fredenslund,Ind.Eng.Chem.Proc.Des.Dev.20(1981)331.[23]rsen,A.Fredenslund,Ind.Eng.Chem.Res.26(1987)2274.[24]P.J.Flory,Principles of Polymer Science,Cornell UniversityPress,Ithaca,NY,1953.[25]M.Mazzotti,V.Kruglov,B.Neri,D.Gelosa,M.Morbidelli,Chem.Eng.Sci.51(10)(1996)1827.[26]G.Froment,K.B.Bischoff,Chemical Reactor Analysis andDesign,2nd Edition,Wiley,New York,1990,p.39. [27]F.Ancillotti,M.Massi Mauri,E.Pescarollo,L.Romagnoni,J.Mol.Catal.4(1978)37.。
著作一:荧光分析法 (第三版)许金钩 王尊本 主编

有机化学1.David A. Evans,* Daniel Seidel, Magnus Rueping, Hon Wai Lam, Jared T. Shaw, and C. Wade Downey, A New Copper Acetate-Bis(oxazoline)-Catalyzed, Enantioselective Henry Reaction, J. AM. CHEM. SOC. 2003, 125, 12692-12693.2. Brian D. Dangel and Robin Pol,Catalysis by Amino Acid-Derived Tetracoordinate Complexes: Enantioselective Addition of Dialkylzincs to Aliphatic and Aromatic Aldehydes, Org. Lett. 2007, 2, 3003.3. Benjamin List, Proline-catalyzed asymmetric reactions, Tetrahedron, 2002, 58, 5573.4. Vishnu Maya, Monika Raj, and Vinod K. Singh, Highly Enantioselective Organocatalytic Direct Aldol Reaction in an Aqueous Medium, Org. Lett. 2007, 9, 2593.5. Sanzhong Luo, Jiuyuan Li, Hui Xu, Long Zhang, and Jin-Pei Cheng, Chiral Amine-Polyoxometalate Hybrids as Highly Efficient and Recoverable Asymmetric Enamine Catalysts, Org. Lett. 2007, 9, 3675.6. Xiao-Ying Xu, Yan-Zhao Wang, and Liu-Zhu Gong, Design of Organocatalysts for Asymmetric Direct Syn-Aldol Reactions, Org. Lett. 2007, 9, 4247.7. Jung Woon Yang, Maria T. Hechavarria Fonseca, Nicola Vignola, and Benjamin List, Metal-Free, Organocatalytic Asymmetric Transfer Hydrogenation of a,b-Unsaturated Aldehydes, Angew. Chem. Int. Ed. 2005, 44, 108–110.8. Giuseppe Bartoli, Massimo Bartolacci, Marcella Bosco, et. al., The Michael Addition of Indoles to r,â-Unsaturated Ketones Catalyzed by CeCl3â7H2O-NaI Combination Supported on Silica Gel, J. Org. Chem. 2003, 68, 4594-4597.9. Jayasree Seayad, Abdul Majeed Seayad, and Benjamin List, Catalytic Asymmetric Pictet-Spengler Reaction, J. AM. CHEM. SOC. 2006, 128, 1086-1087.10. Jingjun Yin, Matthew P. Rainka, Xiao-Xiang Zhang, and Stephen L. Buchwald, A Highly Active Suzuki Catalyst for the Synthesis of Sterically Hindered Biaryls: Novel Ligand Coordination, J. AM. CHEM. SOC. 9 VOL. 124, NO. 7, 2002 1162.11. Ulf M. Lindstro¨m, Stereoselective Organic Reactions in Water, Chem. Rev. 2002, 102, 2751-2772 .12. Sanzhong Luo, Hui Xu, Jiuyuan Li, Long Zhang, and Jin-Pei Cheng, A Simple Primary-Tertiary Diamine-Brønsted Acid Catalyst for Asymmetric Direct Aldol Reactions of Linear Aliphatic Ketones, J. AM. CHEM. SOC. 2007, 129, 3074-3075.13. Xin Cui, Yuan Zhou, Na Wang, Lei Liu and Qing-Xiang Guo, N-Phenylurea as an inexpensive and efficient ligand for Pd-catalyzed Heck and room-temperature Suzuki reactions, TL, 2007, 48, 163.14. Yoshiharu Iwabuchi, Mari Nakatani, Nobiko Yokoyama, and Susumi Hatakeyama, Chiral Amine-Catalyzed Asymmetric Baylis-Hillman Reaction: A Reliable Route to Highly Enantiomerically Enriched (r-Methylene-â-hydroxy)esters, J. Am. Chem. Soc. 1999, 121, 10219-10220.15. Satoko Kezuka, Taketo Ikeno, and Tohru Yamada, Optically Active â-Ketoiminato Cationic Cobalt(III) Complexes: Efficient Catalysts for Enantioselective Carbonyl-Ene Reaction of Glyoxal Derivatives, Org. Lett. 2001, 3, 1937.分析化学16. Lei Liu, Qin-Xiang Guo, Isokinetic relationship, isoequilibrium relationship, and enthalpy-entropy compensation , Chem. Rev. 2001, 101, .17. Sui-Yi Lin, Shi-Wei Liu, Chia-Mei Lin, and Chun-hsien Chen,Recognition of Potassium Ion in Water by 15-Crown-5 Functionalized Gold Nanoparticles, Anal. Chem. 2002, 74, 330-33518. Mikhail V. Rekharsky and Yoshihisa Inoue, Complexation and Chiral Recognition Thermodynamics of 6-Amino-6-deoxy-â-cyclodextrin with Anionic, Cationic, and Neutral Chiral Guests: Counterbalance between van der Waals and Coulombic Interactions, J. AM. CHEM. SOC., 2002, 124: 813-82619. Yu Liu, Li Li, Zhi Fan, Heng-Yi Zhang, Xue Wu, Xu-Dong Guan, Shuang-Xi Liu, Supramolecular Aggregates Formed by Intermolecular Inclusion Complexation of Organo-Selenium Bridged Bis(cyclodextrin)s with Calix[4]arene Derivative, nano letters, 2002, 2:257-262.20. CARLITO B. LEBRILLA, The Gas-Phase Chemistry of Cyclodextrin InclusionComplexes, Acc. Chem. Res. 2001, 34: 653-66121. Jian-Jun Wu, Yu Wang, Jian-Bin Chao, Li-Na Wang, and Wei-Jun Jin. Room Temperature Phosphorescence of 1-Bromo-4-(bromoacetyl) Naphthalene Induced Synergetically by -cyclodextrin and Brij30 in the Presence of Oxygen. The Journal of Physical Chemistry: B, 2004, 108: 8915-8919.22. Xiang-feng Guo, Xu-hong Qian, and Li-hua Jia. A Highly Selective and Sensitive Fluorescent Chemosensor for Hg2+in Neutral Buffer Aqueous Solution. J. Am. Chem. Soc. 2004,126: 2272-2273.23. Yu Wang, Jian-Jun Wu, Yu-Feng Wang, Li-Pin Qin, Wei-Jun Jin. Selective Sensing of Cu (Ⅱ) at ng ml-1level Based on Phosphorescence Quenching of 1-Bromo-2-methylnaphthalene Sandwiched in Sodium Deoxycholate Dimer. Chem. Commun. 2005, 1090-1091.24. Yong-fen Chen and Zeev Rosenzweig(2002) Luminescent CdS Quantum Dots as Selective Ion Probes. Anal. Chem., 74: 5132-513825. Thorfinnur Gunnlaugsson, Mark Glynn, Gillian M. Tocci (née Hussey), Paul E. Kruger, Frederick M. Pfeffer Anion recognition and sensing in organic and aqueous media using luminescent and colorimetric sensors. Coordination Chemistry Reviews 2006, 250: 3094–3117.26. E.M. Martin Del Valle, Cyclodextrins and their uses: a review, Process Biochemistry 2004, 39 : 1033–104627. Ahmet Gu rses, Mehmet Yalcin, Cetin Dogar,Electrocoagulation of some reactive dyes: a statistical investigation of some electrochemical variables, Waste Management 22 (2002) 491–428. K. Lang, J. Mosinger, D.M. Wagnerová, V oltammetric studies of anthraquinone dyes adsorbed at a hanging mercury drop electrode using fast pulse techniques, Coordination Chemistry Reviews 248 (2004) 321–35029. You Qin Li, Yu Jing Guo, Xiu Fang Li, Jing Hao Pan, Electrochemical studies of the interaction of Basic Brown G with DNA and determination of DNA, 2007,71: 123-128.30. P.J. Almeida, J.A. Rodrigues, A.A. Barros, A.G. Fogg, Photophysical properties of porphyrinoid sensitizers non-covalently bound to host molecules; models for photodynamic therapy, Analytica Chimica Acta 385 (1999) 287-293.无机化学31. Silvia Miret, Robert J. Simpson, and Andrew T. McKie, PHYSIOLOGY ANDMOLECULAR BIOLOGY OF DIETARY IRON ABSORPTION, Annu. Rev. Nutr. 2003. 23:283–301.32. Joy J. Winzerling and John H. Law, COMPARATIVE NUTRITION OF IRON AND COPPER, Annu. Rev. Nutr. 1997. 17:501–26.33. Kurt Dehnicke and Andreas Greiner, Unusual Complex Chemistry of Rare-Earth Elements: Large Ionic Radii—Small Coordination Numbers, Angew. Chem. Int. Ed. 2003, 42, No. 12, 1341-1354.34. Todor Dudev, Principles Governing Mg, Ca, and Zn Binding and Selectivity in Proteins, Chem. Rev. 2003, 103, 773-787.35. Maria M. O. Pena, Jaekwon Lee and Dennis J. Thiele, A Delicate Balance: Homeostatic Control of Copper Uptake and Distribution, J. Nutr. 129: 1251–1260, 1999.36. Elza V. Kuzmenkina, Colin D. Heyes, and G. Ulrich Nienhaus, Single-molecule Forster resonance energy transfer study of protein dynamics under denaturing conditions, PNAS, October 25, 2005, vol. 102 _ no. 43 _ 15471–15476.37. Simon Silver, Bacterial resistances to toxic metal ions - a review, Gene 179 (1996) 9-19.38. David A Zacharias, Geoffrey S Baird and Roger Y Tsien, Recent advances in technology for measuring and manipulating cell signals, Current Opinion in Neurobiology 2000, 10:416–421.39. Edward Luk Laran T. Jensen Valeria C. Culotta, The many highways for intracellular trafficking of metals, J Biol Inorg Chem (2003) 8: 803–809.40. JOHN B. VINCENT, Elucidating a Biological Role for Chromium at a Molecular Level, Acc. Chem. Res. 2000, 33, 503-510.41. Mark D. Harrison, Christopher E. Jones, Marc Solioz, Intracellular copper routing: the role of copper chaperones, TIBS 25 – JANUARY 2000, 29-32.42. R.J.P. Williams, My past and a future role for inorganic biochemistry, Journal of Inorganic Biochemistry 100 (2006) 1908–1924.43. Gray H B., ‘Biological Inorganic Chemistry at the Beginning of the 21th Century’, PNAS, 2003, 100(7), 3563-3583.物理化学/应用化学44.Chemistry of Aerogels and Their Applications, Alain C. Pierre and Ge´rard M.Pajonk, Chem. Rev. 2002, 102, -4265.45.Mechanisms of catalyst deactivation, Calvin H. Bartholomew, Applied Catalysis A:General 212 (2001) 17–60.anic chemistry on solid surfaces, Zhen Ma, Francisco Zaera, Surface ScienceReports , 61 (2006) 229–281.47.Heterogeneous catalysis: looking forward with molecular simulation, J.W.Andzelm, A.E. Alvarado-Swaisgood, F.U. Axe, M.W. Doyle, G. Fitzgerald 等,Catalysis Today,50 (1999) 451-477.48.Current Trends in the Improvement and Development of Catalyst PreparationMethods,N. A. Pakhomov and R. A. Buyanov,Kinetics and Catalysis, V ol. 46, No. 5, 2005, pp. 669–683.49.Temperature-programmed desorption as a tool to extract quantitative kinetic orenergetic information for porous catalysts,J.M. Kanervo ∗, T.J. Keskitalo, R.I.Slioor, A.O.I. Krause,Journal of Catalysi s 238 (2006) 382–393.50.Adsorption _ from theory to practice,A. Da˛browski,Advances in Colloid andInterface Science93(2001)135-224.51.Characterization of solid acids by spectroscopy,Eike Brunner,Catalysis Today,38 (1997) 361-376.52.Chemical Strategies To Design Textured Materials: from Microporous andMesoporous Oxides to Nanonetworks and Hierarchical Structures,Galo J. de A. A.Soler-Illia, Cle´ment Sanchez等,Chem. Rev.2002, 102, 4093-4138.53.Solid-State Nuclear Magnetic Resonance,Cecil Dybowski,Shi Bai, and Scott vanBramer,Anal. Chem. 2004, 76, 3263-3268.54.Aerogel applications,Lawrence W. Hrubesh,Journal of Non-Crystalline Solids225_1998.335–342.55.Application of computational methods to catalytic systems,Fernando Ruette,Morella S´anchezb, Anibal Sierraalta, Journal of Molecular Catalysis A: Chemical 228 (2005) 211–225.56.Applications of molecular modeling in heterogeneous catalysis research,Linda J.Broadbelt1, Randall Q. Snurr,Applied Catalysis A: General 200 (2000) 23–46. 57.IR spectroscopy in catalysis,Janusz Ryczkowski,Catalysis Today 68 (2001)263–381.58.The surface chemistry of catalysis: new challenges ahead,Francisco Zaera,Surface Science 500 (2002) 947–965.药学60. Peishan Xie, Sibao Chen, Yi-zeng Liang, Xianghong Wang, Runtao Tian, Roy Upton,Chromatographic fingerprint analysis—a rational approach for quality assessment of traditional Chinese herbal medicine,J. Chromatogr. A 1112 (2006) 171–180.61. Yi-Zeng Lianga, Peishan Xieb, Kelvin Chan, Quality control of herbal medicines, Journal of Chromatography B, 812 (2004) 53–70.62. 刘昌孝, 代谢组学的发展与药物研究开发, 天津药学2005 年4 月第17 卷第2 期.63. 徐曰文,林东海,刘昌孝,代谢组学研究现状与展望,药学学报2005, 40 (9) : 769 – 774。
肿瘤相关巨噬细胞的脂质代谢重编程

四川大学学报(医学版)2021,52(1) :45-49J Sichuan Univ (Med Sci)doi: 10.12182/20210160202肿瘤相关巨噬细胞的脂质代谢重编程+赵昆,时荣臣,缪洪明4中国人民解放军陆军军医大学(第三军医大学)基础医学院生物化学与分子生物学教研室(重庆400038)【摘要】肿瘤相关巨唾细胞(tumor associated macrophages, TAMs)是实质肿瘤中最常见的间质细胞类型之一,且与 肿瘤微环境的免疫抑制状态有着紧密联系,并促进肿瘤的恶性进展。
TAMs内的代谢发生了重编程,并且参与调控其自身 的极化以及相应的功能表型。
本文详细论述了 TAMs中包括三酰甘油、脂肪酸及其衍生物、胆固醇和磷脂在内的脂质代 谢重编程以及它们对肿瘤进展的调控。
然而,肿瘤细胞与肿瘤微环境间质细胞的代谢极具异质性。
肿瘤细胞与间质细胞 之间脂代谢重编程的异同点以及重编程如何调控细胞活性的机制值得深人探索。
同时,综合考虑肿瘤不同的组织类型、不同的发展阶段,精准靶向干预TAMs脂质代谢重编程,促进TAMs向M l样巨噬细胞极化,将成为代谢调节肿瘤免疫治疗 的新策略。
【关键词】肿瘤相关巨噬细胞 免疫抑制 脂质代谢重编程 肿瘤进展A Review of the Lipid Metabolism Reprogramming in Tumor Associated Macrophages Z H A O K u n, SH I R ong-chen,M IA O H o n g-m in g A. D e p a r tm e n t o f B io c h e m is try a n d M o le c u la r B io lo g y y S ch o o l o f B a sic M e d ic in e, A r m y M e d ic a lU n iversity (T h ird M ilita ry M e d ica l U n iversity)y Chongqing 400038, ChinaACorrespondingauthor,E-mail:*********************【Abstract】Tumor associated macrophages (TAMs) are one of the most common types of stromal cells in solid tumors. They are closely related to the immunosuppressive status of tumor microenvironment and potentiate the malignant progress of tumors. Studies have shown that metabolism in tumor associated macrophages has been reprogrammed and involved in the regulation of their own polarization and corresponding functions and phenotypes.Metabolic reprogramming refers to the alteration of key enzymes activity, substrate and its associated metabolites’concentration in a certain metabolic pathway, which accounts for the disorder of original metabolic states. In this paper, we mainly concentrated on the lipid metabolic reprogramming of TAMs, including triglycerides, fatty acids and their derivatives, cholesterol, phospholipids, and their regulations on tumor progression. However, the metabolism of tumor and tumor microenvironment cells is highly heterogeneous. It is worthy of further exploration on the similarities and differences of lipid metabolism reprogramming between stromal cells and tumor cells, and the mechanism of how reprogramming modulates cell activity. It will be a new strategy for immunotherapy of tumor with metabolic intervention to accurately target the lipid metabolism reprogramming of TAMs, so as to promote the polarization of TAMs to Ml like macrophages, when synthetically considering the diverse types of tumors and different stages of development.[K e y w o rd s] Tum or associated m acrophages Im m unosuppression Lipid m etabolism reprogramming Tumor progression肿瘤相关巨唾细胞(tumor associated macrophages, TAMs),—般指实体肿瘤微环境中的巨噬细胞,在实体肿 瘤内浸润的髓源细胞中占有最大比例,并与癌症患者的 不良预后密切相关。
高分子专业英语词汇汉译英(精)

--- 均方末端距mean-aquare end-to-end distance 均方末端距- 非交联的uncross-linked 非交联的- 三维有序的three-dimensionally ordered 三维有序的- 三乙基硼氟酸羊triethyloxonium-borofluoride 三乙基硼氟酸羊 - 射线光X-ray x 射线 x 光- 缨状微束理论fringed-micelle theory 缨状微束理论- 折叠链片晶理论folded-chain lamella theory 折叠链片晶理论 - 逐步聚合step-growth polymerization 逐步聚合(表面)发粘的, 粘连性tacky (表面)发粘的 , 粘连性(空间)排布,排列arrangement (空间)排布,排列(链)引发initiation (链)引发(链)终止terminate (链)终止(链)转移,(热)传递transfer (链)转移,(热)传递(生)面团,揉好的面dough (生)面团,揉好的面 (作用于分子间的intermolecular (作用于分子间的氨基,氨基的amino 氨基,氨基的氨基甲酸酯urethane 氨基甲酸酯把…相互连接起来连接interlink 把…相互连接起来连接半晶semicrystalline 半晶半径radius 半径饱和saturation 饱和苯基锂phenyllithium 苯基锂苯基钠phenyl sodium 苯基钠变化,改变variation 变化,改变变形deformation 形变变形性,变形能力deformability 变形性,变形能力表面活性剂surfactant 表面活性剂表征成为…的特征characterize 表征成为…的特征玻璃(态)的glassy 玻璃态的玻璃化温度glass transition temperature 玻璃化温度玻璃态glassy 玻璃(态)的玻璃态的glassy state 玻璃态不饱和的unsaturated 不饱和的不规则性,不均匀的irregularity 不规则性,不均匀的不均匀的,非均匀的heterogeneous 不均匀的,非均匀的不了或缺的indispensable 不了或缺的不完全的imperfect 不完全的参数parameter 参数侧基pendant group 侧基缠结,纠缠entanglement 缠结,纠缠产率yield 产率超声波ultrasonic 超声波超速离心(分离)ultracentrifugation 超速离心(分离)撤出evacuate 撤出沉淀,澄清settle 沉淀,澄清沉降(法)sedimentation 沉降(法)衬里,贴面line 衬里,贴面成分ingredient 成分成型shaping 成型尺寸dimension 尺寸尺寸稳定性dimensional stability 尺寸稳定性稠度,粘稠度consistency 稠度,粘稠度纯度purity 纯度醇(碱金属)烯催化剂Alfin catalyst 醇(碱金属)烯催化剂催化剂,触媒catalyst 催化剂,触媒脆的,易碎的brittle 脆的,易碎的错位,位错dislocation 错位,位错大分子,高分子macromelecule 大分子,高分子单官能度的monofunctional 单官能度的单键single bond 单键单体monomer 单体单轴的uniaxial 单轴的弹性模量elastic modulus 弹性模量弹性体elastomer 弹性体弹性指数slastic parameter 弹性指数当量的,化学计算量的stoichiometric 当量的,化学计算量的导电材料conductive material 导电材料等规立构的isotactic 等规立构的丁二烯butadiene 丁二烯丁基锂butyllithium 丁基锂定向,取向orient 定向,取向定向orientation 定向动力学kinetics 动力学动力学链长kinetic chain length 动力学链长断裂rupture 断裂堆积物,沉积deposit 堆积物,沉积堆砌packing 堆砌多分散的polydisperse 多分散的多分散性polydispersity 多分散性多官能度的polyfunctional 多官能度的多孔性,孔隙率porosity 多孔性,孔隙率二(元)胺diamine 二(元)胺二(元)醇diol 二(元)醇二(元)酸diacid 二(元)酸二次成型secondary shaping operation 二次成型二聚物(体)dimer 二聚物(体)二烯烃diolefin 二烯烃二元的dibasic 二元的反应物,试剂reactent 反应物,试剂反应性,活性reactivity 反应性,活性反应性的,活性的reactive 反应性的,活性的芳香(族)的aromatic 芳香(族)的非弹性的nonelastic 非弹性的分级fractionation 分级分解,分散,分离disintegrate 分解,分散,分离分解decomposition 分解分类(法)categorization 分类(法)分散剂dispersant 分散剂分子量molecular weight distribution 分子量分布分子量分布molecular weight 分子量粉状的powdery 粉状的副作用side reaction 副作用改性modify 改性隔离基团spacer group 隔离基团各项同性的isotropic 各项同性的功能聚合物functional polymer 功能聚合物功能聚合物functionalized polymer 功能聚合物共聚(合)copolymerization 共聚(合)共聚物copolymer 共聚物构象conformation 构象固有的intrinsic 固有的官能团functional group 官能团光敏剂photosensitizer 光敏剂光气,碳酰氯phosgene 光气,碳酰氯光散射light scattering 光散射合成synthesis 合成合成synthesize 合成合成的synthetic 合成的核磁共振nuclear magnetic resonance 核磁共振核径迹探测器nuclear track detector 核径迹探测器红外光谱法infrared spectroscopy 红外光谱法花纹,图样式样pattern 花纹,图样式样缓释剂corrosion inhibitor 缓释剂机理mechanism 机理基体,结晶crystal 基体,结晶基体,母体,基质,矩阵matrix 基体,母体,基质,矩阵挤出extrusion 注射成型挤压squeeze 挤压加成聚合物,加聚物addition polymer 加成聚合物,加聚物加工,成型processing 加工,成型加重,恶化aggravate 加重,恶化夹杂(带)的occluded 夹杂(带)的假定的,理想的,有前提的hypothetical 假定的,理想的,有前提的间歇式的intermittent 间歇式的碱金属alkali metal 碱金属键断裂能bond dissociation energy 键断裂能降解depropagation 降解交联crosslinking 交联胶体colloid 胶体搅拌agitation 搅拌结构,组织texture 结构,组织结晶的crystalline 晶体,晶态,结晶的,晶态的结晶性,结晶度crystallinity 结晶性,结晶度解除,松开release 解除,松开解聚depolymerization 解聚介质中等的,中间的medium 介质中等的,中间的界限,范围boundary 界限,范围晶体,晶态,结晶的,晶态的crystalline 结晶的竞聚率reactivity ratio 竞聚率聚苯烯polypropylene 聚苯烯聚苯乙烯polystyrene 聚苯乙烯聚丁烯polybutene 聚丁烯聚合(物)的polymeric 聚合(物)的聚合度degree of polymerization 聚合度聚合物【体】,高聚物polymer 聚合物【体】,高聚物聚氯乙烯polyvinylchloride 聚氯乙烯聚酰胺polyamide 聚酰胺聚乙烯polyethylene 聚乙烯聚乙烯醇polyvinyl alcohol 聚乙烯醇聚酯化(作用)polyesterification 聚酯化(作用)开链unzippering 开链开始,着手commence 开始,着手抗静电剂antistatic agent 抗静电剂抗氧剂antioxidant 抗氧剂抗张强度tensile strength 抗张强度控制释放controlled release 控制释放口模成型dieforming 口模成型扩散diffuse 扩散拉直,拉长stretch 拉直,拉长冷冻水chilled water 冷冻水离解dissociate 离解离心centrifuge 离心离子ion exchange resin 离子交换树脂离子的ionic polymerization 离子型聚合离子交换树脂ion 离子离子型聚合ionic 离子的理想的,概念的ideal 理想的,概念的力学性能,机械性能mechanical property 力学性能,机械性能立构规整性【度】srereoregularity 立构规整性【度】连锁反应chain reaction 连锁反应链段segment 链段链段segment 链段链间的interchain 链间的链终止chain termination 链终止流动性mobility 流动性流体静力学hydrostatic 流体静力学硫化vulcanization 硫化络合物complex 络合物氯(气)chlorine 氯(气)氯乙烯vinyl 乙烯基(的)密度density 密度密封seal 密封模塑成型moulding 模塑成型模型model 模型逆流countercurrent 逆流黏弹态viscoelastic 黏弹性的黏弹性的viscoelastic state 黏弹态黏度viscosity average molecular weight 黏均分子量黏均分子量viscosity 黏度黏流态viscofluid state 黏流态凝胶 gel 凝胶农药,化肥 agrochemical 排列成行 align 配方 formulation 喷洒sprinkle 喷洒片晶 platelet 片晶平衡 equilibrium 潜在的 latent 平衡潜在的嵌入,埋入,包埋氢键排列成行配方农药,化肥嵌入,埋入,包埋 imbed 强度 strength 强度氢(气)hydrogen bonding 氢键 hydrogen 缺陷 defect 缺陷氢(气)取代,代替substitution 取代,代替热成型 thermoforming 热固性的 thermoset 热解 pyrolysis 热成型热固性的热解热塑性的热传递 heat transfer 热传递热力学地thermondynamically 热力学地热塑性的 thermoplastic 溶剂 solvent 溶解 dissolution 溶解度 solubility 溶胀 swell 熔化的 molten 柔量 compliance 溶胀熔化的柔量溶剂溶解溶解度溶胀的 swollen 溶胀的柔软的 flexible 柔软的三苯甲基钾 triphenylenthyl potassium 三苯甲基钾三聚物(体)trimer 三聚物(体)三氯化铁三元的,叔(特)的三氯化铁 titanium trichloride 三元的,叔(特)的 tertiary 筛子,筛分scalp 熵 entropy 熵伸长率,延伸率 elongation 渗透性 permeability 渗透性生物(学)的 biological 生物医学的 biomedical 食盐 common salt 食盐生长链,活性链growing chain 生物(学)的生物医学的生长链,活性链伸长率,延伸率筛子,筛分使…变形,扭曲 distort 使脱氢 dehydrogenate 收缩 retract 收缩使…变形,扭曲使脱氢数均分子量使…溶解 dissolve 使…溶解数均分子量 number average molecular weight 双键 double bond 双键四氯化钛 titanium tetrachloride 四氯化钛四氢呋喃 tetrahydrofuran 塑料 plastics 塑料碎屑,碎片 fragment 羧基 carboxyl 羧基羧基酸 hydocy acid 羧基酸缩(合)聚(合)polycondensation 缩合聚合物,缩聚物condensation polymer 太阳能 solar energy 太阳能炭 char 炭特性 peculiarity 烃基hydroxyl 统计的 statistical 涂覆 coating 涂覆脱单塔 stripping tower 脱水 dewater 脱水外形,轮廓 contour 外形,轮廓烷基铝 aluminum alkyl 微晶 crystallite 稳定剂stabilizer 稳定性 stability 稳定性污物 contaminant 污物无定型的,非晶体的amorphous 无规降解 random decomposition 无规立构的 atactic 无规立构的无规线团random coil 无规线团无机聚合物 inorganic polymer 烯丙基 allyl 烯丙基烯烃的olefinic 烯烃的细分区分 subdivide 纤维 fiber 线团 coil 线团纤维细分区分微晶稳定剂烷基铝脱单塔特性烃基同时,同步统计的碎屑,碎片四氢呋喃缩(合)聚(合)缩合聚合物,缩聚物同时,同步 simultaneously 无定型的,非晶体的无规降解无机聚合物酰胺化(作用)amidation 酰胺化(作用)线团状的 coiling 线团状的相互作用相互作用 interaction 橡胶 rubber 橡胶想象,推测 imagine 想象,推测橡胶态的 rubbery 橡胶态的消除,打开,除去eliminate 形变 deformation 变形形态(学)morphology 形态(学)型柸 parison 型柸性能,行为 behavior 性能,行为性能,特征 performance 性能,特征絮凝剂flocculating agent 压延 calendering 衍射 diffraction 氧鎓羊 oxonium 药品,药物 drug 液晶 liquid crystal 液晶依数性 colligative 乙烯基醚 vinyl chloride 异丁烯 isobutylene 异氰酸酯 isocyanate 阴(负)离子的 anionic 引发剂 initiator 引发剂引力,吸引attraction 硬度 hardness 油轮,槽车 tanker 淤浆 slurry 淤浆硬度油轮,槽车引力,吸引异丁烯异氰酸酯阴(负)离子的依数性乙烯基醚氯乙烯异丙醇金属,异丙氧化金属乙烯基(的)vinyl ether 压延成型压延衍射氧鎓羊药品,药物,药物的,医药的药品,药物絮凝剂旋转,回旋 gyration 旋转,回旋压延成型calendering 消除,打开,除去小球,液滴,颗粒 globule 小球,液滴,颗粒阳(正)离子的 cationic 阳(正)离子的药品,药物,药物的,医药的pharmaceutical 异丙醇金属,异丙氧化金属 isopropylate 有规立构的,立构规整性的stereoregular 有规立构的,立构规整性的运动,流动 mobilize 运动,流动杂质impurity 杂质载体 carrier 载体增进,改善 improve 增进,改善粘稠的 viscous 粘稠的照射,辐射 irradiation 真是的 real 真是的照射,辐射争论,争议 controversy 争论,争议正[阳]离子 cation 正[阳]离子正的,阳(性)的 positive 正的,阳(性)的脂肪(族)的 aliphatic 脂肪(族)的酯化(作用)esterification 酯化(作用)中性的 neutral 中性的重复单元重均分子量主链,骨干助催化剂挤出转化率转化自由基聚合种类,类型 category 种类,类型重复单元 repeating unit 主链,骨干 backbone 助催化剂 cocatalyst 注射成型 extrusion 转化 conversion 转化率conversion 转矩 torsion 转矩自由基阻燃剂最佳的,最佳值[点,状态] 最小化最小值,最小的模型活化(作用)重均分子量 weight average molecular weight 自由基radical polymerization 自由基聚合 radical 阻燃剂 flame retardant 最小化 minimise ( 模型 mo(ulding 最佳的,最佳值[点,状态]optimum 最小值,最小的 minimum 活化(作用)activation 手风琴手风琴。
MDSC的免疫调节机制及其在免疫治疗中的作用

MDSC的免疫调节机制及其在免疫治疗中的作用作者:李诗杨志刚来源:《中国医学创新》2017年第13期【摘要】肿瘤微环境由通过癌细胞和周围基质细胞之间复杂的相互作用产生的免疫抑制性网络组成。
这种环境的一个关键组成部分是髓源性抑制细胞(MDSC),代表未成熟骨髓细胞的异质群体,在分化的不同阶段停滞,并响应各种肿瘤因子而扩增。
此外,这些细胞获得抑制表型,表达抗炎细胞因子和活性氧和氮物质,并抑制T细胞免疫应答。
MDSC在调节免疫效应细胞和恶性细胞之间的相互作用中发挥不同的作用,其数量增加与肿瘤发生进展,不良预后和免疫治疗策略有效性降低相关。
了解MDSC的免疫调节功能及机制有助于探求有效的免疫治疗策略。
【关键词】髓源抑制性细胞;肿瘤;免疫调节;免疫治疗【Abstract】 Tumor microenvironment is composed of immunosuppressive networks produced by complex interactions between cancer cells and surrounding stromal cells.A key component of the environment is myeloid-derived suppressor cells(MDSCs),heterogeneous populations representing immature bone marrow cells,stagnating at different stages of differentiation,and amplifying in response to various tumor factors.In addition,these cells obtained inhibition of phenotype,expressed anti-inflammatory cytokines,reactive oxygen species and nitrogen substances,and inhibited the T cell immune response.MDSC plays a different role in regulating the interaction between immune effector cells and malignant cells,and the expansion of MDSCs is associated with tumor progression, poor prognosis and reduced efficacy of immunotherapy strategies.Understanding the immune function and mechanism of MDSC can help to explore effective immunotherapy strategies.【Key words】 Myeloid-derived suppressor cells; Tumor; Immunomodulation;ImmunotherapyFirst-author’s address:Affiliated Hospital of Guangdong Medical University,Zhanjiang 524003,Chinadoi:10.3969/j.issn.1674-4985.2017.13.0401 MDSC的生物学功能及表型特征髓源性抑制细胞(myeloid-derived suppressor cells,MDSCs)作为专业术语在2007年第一次被用于描述癌症患者体内富含的骨髓来源的非淋巴细胞免疫抑制细胞群体。
《地理信息系统--原理、方法和应用》 邬伦等 参考书目

参考文献1.书和专著[德]阿.赫特纳(王兰生译),地理学——它的历史、性质和方法,1997,北京:商务印书馆[俄]K.A. 萨里谢夫(李道义译),地图制图学概论,1982,北京:测绘出版社[美]A. H. 罗宾逊,R. D.塞尔,J.L.莫里逊,P.C.墨尔克(李道义、刘耀珍译),地图学原理,1989,北京:测绘出版社[美]D.J.沃姆斯利、G.J.刘易斯(王兴中、郑国强、李贵才译),行为地理学导论,1988,西安,陕西人民出版社[美]R.哈特向(黎樵译),地理学性质的透视,1997,北京:商务印书馆[美]T.哈默格兰(曾增强译),数据仓库技术,1998,北京:中国水利水电出版社[美]丹尼斯.伍德(王志弘、李根芳、魏庆嘉译),地图的力量,2000,北京:中国社会科学出版社[美]杰克.吉多、詹姆斯.P.克莱门特(张金成译),成功的项目管理,1999,北京:机械工业出版社[美]尼葛洛庞帝(胡泳、范海燕译),数字化生存,1997,海口:海南出版社[日]遥感研究会(刘勇卫、贺雪鸿译),遥感精解,1993,北京:测绘出版社[英]大卫.哈维(高泳源、刘立华、蔡运龙译),地理学中的解释,1996,北京:商务印书馆Andrej Vckovski, Interoperatable and Distributed Processing in GIS, 1998, London: Taylor & FrancisAndrew S. Tanenbaum,Computer Networks,1996,北京清华大学出版社Andrew S. Tanenbaum,Distributed Operating Systems,1996,北京清华大学出版社C. Dana Tomlin,Geographic Information Systems and Cartographic Modeling,1990,Englewood Cliffs,New Jersey:Prentice-Hall Inc.Christopher B. Jones, Geographical Information Systems and Computer Cartography,1997, Addison Wesley Longman Ltd.D.R.F. Taylor, Policy Issues in Modern Cartography, 1998, Oxford: Elsevier Science LtdGrady Booch,Object-Oriented Analysis and Design with Applications,1994,Redwood City,CA:The Benjamin/Cummings Publishing Company,Inc.Hilary M. Hearnshaw & Divid J. Unwin,Visualization in Geographical Information Systems,1994,Chichester:John Wiley & SonsIan Masser,Harlan J. Onsrud,Diffusion and Use of Geographic Information,Dordrecht, 1992,Kluwer Academic PublishersJeffrey D. Ullman & Jennifer Widom, A First Course in Database Systems, 1998,北京:清华大学出版社Jonathan Raper,Three Dimensional Applications in Geographical Information Systems,1989,London: Taylor & FrancisKenneth R. Castleman, Digital Image Processing, 1998,北京:清华大学出版社Leung, Yee,Intelligent Spatial Decision Support Systems. 1997,Berlin: Springer M. Birkin , G. Clarke , M. Clarke & A Wilson , Intelligent GIS , Location Decisions and Strategic Planning , 1996, Cambridge, GeoInformation International M.F.Goodchild & D.W.Rhind, Geographical Information Systems: Principles and Applications. 1991,London: LongmanManfred M. Fischer & Peter Nijkamp,Geographic Information Systems, Spatial Modelling and Policy Evaluation,Berlin:Springer-VerlagMarc van Kreveld, Jurg Nievergelt, Thomas Roos & Peter Widmayer, Algorithmic Foundation of Geographic Information Systems, 1997, Berlin:Springer Martien Molenaar, An Introdcution to the Theory of Spatial Object Modelling, 1998, London:Taylor & Francis Ltd.Massimo Craglia & Harlan Onsrud, Geographic Information Research: Trans-Atlantic Perspectives ,1999, Bristol:Taylor & FrancisMichael F. Worboys, GIS : A Computing Perspective ,1995,London:Taylor & Francis Ltd.Michael N. DeMers, Fundamentals of Geographic Information Systems,1997,New York:John Wiley & Sons Inc.Michael Stonebraker & Dorothy Moore(杨冬青、唐世渭、裴芳译),对象-关系数据库管理系统——下一个浪潮,1997,北京:北京大学出版社Michel Scholl & Agnes Woisard ,Advances in Spatial Databases,1997,Berlin:SpringerNabil R. Adam & Aryya Gangopadhyay, Database Issues in Geographic Information Systems, 1997, Dordrecht: Kluwer Acadamic PublishersP. van Oosterom, Reactive Data Structure for Geographic Information Systems, 1993, New York: Oxford University Press.P.A.Buffough & R.A. McDonnel, Principles of Geographical Information Systems, 1998, New York: Oxford PressP.A.Buffough, Principles of Geographical Information Systems for Land Resource Assessment,1986, Oxford: Clarendon PressPeter Coad & Edward Yourdon(邵维忠、廖钢城、李力译),面向对象的分析,1992,北京,北京大学出版社Peter Coad & Edward Yourdon(邵维忠、廖钢城、李力译),面向对象的设计,1992,北京,北京大学出版社Robert Lloyd, Spatial Cognition, 1997, Dordrecht: Kluwer Acadamic Publishers S.Fotheringham & P.Rogerson, Spatial Anaysis and GIS,1994,Lodon:Taylor and FrancisSamet H.. Applications of spatial data structure. Computer Graphics, Image Processing , and GIS, Massachusetts :Addison-Wesley Publishing Company, Inc. , 1994.Samet H.. The design and analysis of spatial data structure . Massachusetts: Addison-Wesley Publishing Company, Inc. , 1990.Stewart Fortheringham & Peter Rogerson,Spatial Analysis and GIS,1994,London:Taylor & Francis Ltd.Timothy W. Foresman, The History of Geographic Information Systems:Perspectives from the Pioneers, 1997,Englewood Cliffs,New Jersey:Prentice-Hall Inc.Tor Bernhardsen,Geographic information systems : an introduction,1999,New York : WileyWolfram, Stephen,Theory and applications of cellular automata,1986,Singapore,World ScientificZhou Qiming,Li Zhilin,Lin Hui&Shi Wenzhong, Spatial Information Technology Towards 2000 and Beyond,1998,Berkeley:CPGIS边馥苓,地理信息系统原理和方法,1996,北京,测绘出版社陈俊、宫鹏,实用地理信息系统——成功地理信息系统的建设与管理,1998,北京:科学出版社陈述彭、鲁学军、周成虎,地理信息系统导论,1999,北京:科学出版社承继成、李琦、易善桢,国家空间信息基础设施与数字地球,1999,北京:清华大学出版社崔伟宏,空间数据结构研究,1995,北京:中国科学技术出版社崔屹,图像处理与分析——数学形态学方法及应用,2000,北京:科学出版社杜道生、陈军、李征航,RS GIS GPS的集成与应用,1995,北京:测绘出版社宫鹏,城市地理信息系统:方法与应用,1996,Berkeley:CPGIS宫鹏、史培军、浦瑞良、郭华东,对地观测技术地球系统科学,1996,北京:科学出版社龚健雅,当代GIS的若干理论与技术,1999,武汉:武汉测绘大学出版社郭德方,遥感图像的计算机处理和模式识别,1987,北京,电子工业出版社郭仁中,空间分析,2000,武汉:武汉测绘大学出版社胡毓钜、龚剑文、黄伟,地图投影,1981,北京:测绘出版社黄杏元、汤勤,地理信息系统概论,1990,北京:高等教育出版社科技部国家遥感中心,地理信息系统与管理决策,2000,北京:北京大学出版社李德仁、龚健雅、边馥苓,地理信息系统导论,1993,北京:测绘出版社南京大学、北京大学、中山大学、西北大学地理系,测量学与地图学,1979,北京:人民教育出版社齐东旭,分形及其计算机生成,1994,北京:科学出版社邵维忠、杨芙清,面向对象的系统分析,1998,北京:清华大学出版社史文中,空间数据误差处理的理论与方法,1998,北京:科学出版社宋小冬、叶嘉安,地理信息系统及其在城市规划与管理中的应用,1995,北京:科学出版社孙铁成,计算机与法律,1998,北京:法律出版社王长耀、郑兴年、崔伟宏等,资源环境动态遥感与模型分析试验研究,1993,北京:宇航出版社王立福、张世琨、朱冰,软件工程——技术、方法与环境,1997,北京:北京大学出版社王桥、毋河海,地图信息的分形描述与自动综合研究,1998,武汉:武汉测绘大学出版社邬伦、任伏虎、谢昆青、程承旗,地理信息系统教程,1994,北京:北京大学出版社徐绍铨、张华海、杨志强、王泽民,GPS测量原理及应用,1998,武汉:武汉测绘大学出版社严蔚敏、吴伟民,数据结构,1992,北京:清华大学出版社阎正,城市地理信息系统标准化指南,1998,北京:科学出版社杨东援,交通规划决策支持系统,1997,上海:同济大学出版社应明,计算机软件的版权保护,1991,北京:北京大学出版社张超、陈丙咸,地理信息系统,1995,北京:高等教育出版社张海藩,软件工程导论,1998,北京:清华大学出版社张力果、赵淑梅、周占鳌,地图学,1990,北京:高等教育出版社张永生,遥感图像信息系统,2000,北京:科学出版社中国21世纪议程管理中心,中国地理信息元数据标准研究,1999,北京:科学出版社周成虎,孙战利,谢一春,地理元胞自动机研究,1999,北京:科学出版社周成虎、骆剑承、杨晓梅、杨存建、刘庆生,遥感影像地学理解与分析,1999,北京:科学出版社周培德,计算几何——算法分析与设计,1999,北京:清华大学出版社周忠谟、易杰军、周琪,GPS卫星测量原理与应用,1991,北京:测绘出版社2.标准和规范Capability Maturity Model SM for Software, Version 1.1,1993,CMU-SEIOpenGIS® Simple Features Specification For OLE/COM, Revision 1.1, 1999, Open GIS Consortium, Inc.The OpenGIS™Abstract Specification, Version 4, 1999, Open GIS Consortium, Inc.OMG Unified Modeling Language Specification,Version 1.3,1999,Object Management Group Inc.The Common Object Request Broker:Architecture and Specification,Version 2.1, Object Management Group Inc.ISO/TC 211 Geographic Information/Geomatics,1998,ISO3.杂志Int. J. Geographical Information ScienceCartography and Geoghraphic Information地理科学进展地理学报武汉测绘科技大学学报测绘学报遥感学报Int. J. Remote SensingPhotogrammetric Engineering and Remote Sensing4.Websitehttp://www.statkart.no/isotc211/m.emr.ca5.论文A. Sheth & J. Larson, Federated database systems for managing distributed, heterogeneous,and autonomous databases. ACM Computing Surveys, 1990, 22(3).Brinkhoff T. and Kriegel H. P. et al. Multi-step processing of spatial joins. In the processing of the ACM SIGMOD International Conference on Management of Data, Minneapolis MN,1994Buffough,P.A,Development of Intelligent Geographical Information Systems, Int. J. of Geographical Information Systems, 1992,6David M. Mark & Max J. Egenhofer, Modeling Spatial Relations Between Lines and Regions: Combining Formal Mathematical Models and Human Subject Testing, Cartography and Geographic Information Systems, 1995, 21(4)Elisabeth S. Nelson , A Cognitive Map Experiment : Mental Representation and the Encoding Process, Cartography and Geographic Information Systems, 1996, 23(4) Eric Sheppard, GIS and Society: Towards a Research Agenda, Cartography and Geographic Information Systems, 1995, 22(1)G. Alonso & C. Hagen, Geo-Opera: Workflow Concepts for Spatial Processes, In the proceeding of Advances in Spatial Databases,1995Georg Kosters, Bernd-uwe Pagel, & Hans-werner Six, GIS-application Development with GeoOOA, Int. J. Geographical Information Science, 1997,11(4)I. D. Moore, R. B. Grayson & A. R. Ladson, Digital Terrain Modelling: A Review of Hydrological Geomorphological and Biological Application, Hydrological Processes, 1991,5J. C. Hinter, GIS and Remote Sensing Integration for Environmental Applications, Int. J. Geographical Information Systems, 1996,10(7)J. Fairfield & P. Leymarie,Drainage Networks from Grid Digital Elevation Models,Water Resource Research,1991,27K. Koperski, & J. Han, Discovery of Spatial Association Rules in Geographic Information Databases. In the proceeding of Advances in Spatial Databases,1995 L. E. Band, Topographic partitioning of watersheds with digital elevation models,Water Resources Research, 1986,22M.P. Amstrong, & P.J.Densham, Database orgnazation strategies for spatialdecision support systems, Int. J. of Geographical Information Systems, 1990,4 Oliver Gunther & Volker Gaede, Oversize Shelves: a Storage Technique for Large Spatial Data Objects, Int. J. Geographical Information Science, 1997,11(1) Stefanakis E.,et al. Point representation of spatial objects and query window extension: a new technique for spatial access methods. International Journal Geographical Information Science, 1997, 11(6)V.B. Robinson & A.U. Frank, Expert Systems for Geographical Information Systems, Photogrammetric Engineering and Remote Sensing, 1987,53Yuemin Ding & Paul J. DENSHAM, Spatial Strategies for Parallel Spatial Modelling, Int. J. of Geographical Information Systems, 1996,10(6)陈常松、何建帮,面向GIS数据共享的概念模型设计研究,遥感学报,1999,3(3)陈友飞、许世远,因特网上的地理学资源及其开发,地理学报,1999,54(3)戴洪磊、吴守荣、徐泮林、郭金运,GIS中平面线位误差带的可视化表达,中国图像图形学报,1999,4(3)邸凯昌、李德仁、李德毅,空间数据发掘和知识发现的框架,武汉测绘科技大学学报,1997,22(4)龚建华、林辉、肖乐斌、谢传节,地学可视化探讨,遥感学报,1999,3(3)韩海洋、龚建雅、袁相儒,Internet环境下用Java/JDBC实现地理信息的互操作与分布式管理及处理,测绘学报,1999,28(2)黄波、林辉,GeoSQL:一种可视化空间扩展SQL查询语言,武汉测绘科技大学学报,1999,24(3)黎夏、叶嘉安,约束性单元自动演化CA模型及可持续城市发展形态的模拟,地理学报,1999,54(7)李德仁,信息高速公路、空间数据基础设施与数字地球,测绘学报,1999,28(1)李德仁、关泽群,将GIS数据直接纳入图像处理,武汉测绘科技大学学报,1999,24(3)鲁学军、周成虎、龚建华,论地理空间形象思维,地理学报,1999,54(5)闾国年、钱亚东、陈钟明,基于栅格数字高程模型提取特征地貌技术研究,1998,地理学报,53(6)齐清文、张安定,论地图学知识创新体系的构建,地理科学进展,1999,18(1)王晓栋、崔伟宏,数字地球的时空维实现,地理学报,1990,18(2)王之卓,从测绘学到Geomatics,武汉测绘科技大学学报,1998,23(4)杨群、阎国年、陈钟明,地理信息数据仓库的技术研究,中国图像图形学报,1999,4(8)余生晨、刘大有、刘洪,山脊线与山谷线的计算机自动检测,中国图像图形学报,1999,4(8)袁相儒、龚建雅、林辉、陈莉丽,异构地理信息处理环境互操作的Internet GIS方法,武汉测绘科技大学学报,1999,24(3)张保钢、朱波、朱光,GIS中位置信息的通用数据质量模型及其质量控制,武汉测绘科技大学学报,1999,24(2)张新生、何建邦,城市空间增长与土地开发时空格局,遥感学报,1997,1(2)。
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R. Alur and பைடு நூலகம். Lee (Eds.): EMSOFT 2003, LNCS 2855, pp. 35–50, 2003. c Springer-Verlag Berlin Heidelberg 2003
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A. Benveniste et al.
particular, difficulties arise when the target architecture for the embedded system has a distributed nature that badly matches the synchronous assumption because of large variance in computation and communication times and because of the difficulty of maintaining a global notion of time. This is increasingly the case for many important classes of embedded applications in avionics, industrial plants, and the automotive industry. Here, multiple processing elements operating at different clock frequencies are distributed on an extended area and connected via communication media such as busses (e.g., CAN for automotive applications, ARINC for avionics, and Ethernet for industrial automation) or serial links. Busses and serial links can, however, be carefully designed to comply with a notion of global synchronization as the family of Time-Triggered Architectures (tta), introduced and promoted by H. Kopetz [17], testifies. A synchronous implementations must be conservative, forcing the clock to run as slow as the slowest computation/communication process (worst-case approach). The overhead implied by time-triggered architectures and synchronous implementations is often enough to convince designers to use asynchronous communication architectures such as the ones implemented by the busses mentioned above. We argue that imposing an “homogeneous” design policy, such as the fully synchronous approach, on complex designs will be increasingly difficult. Heterogeneity will manifest itself at the component level where different models of computation may be used to represent component operation and, more frequently, at different levels of abstraction, where, for example, a synchronous-language specification of the design may be refined into a globally asynchronous locally synchronous (GALS) architecture. In this paper, we provide a mathematical framework for the heterogeneous modeling of reactive and real-time systems to allow freedom of choice between different synchronization policies at different stages of the design. The focus of our framework is handling communication and coordination among heterogeneous processes in a mathematically sound way. Interesting work along similar lines has been the Ptolemy project [13,22], the MoBIES project [1], the ModelIntegrated Computing (MIC) framework [16], and Interface Theories [12]. Our main contributions are a mathematical model for heterogeneous system built as a variation of the “Tagged-Signal Model” of Lee and SangiovanniVincentelli [21] (in this paper, called the LSV model) and a set of theorems that support effective techniques to generate automatically correct-by-construction adaptors between designs formulated using different design policies. We illustrate these concepts with two applications that are of particular relevance for the design of embedded systems: the deployment of a synchronous design over a GALS architecture and over a so-called Loosely Time-Triggered Architecture (Ltta) [7]. The idea followed in these examples is to abstract away from the synchronous specifications the constraints among events of different signals due to the synchronous paradigm and, then, to map the “unconstrained” design into a different architecture characterized by a novel set of constraints among events. In doing so, we must make sure that, when we remap the design, the intended “behaviour” of the system is retained. To do so we introduce a formal notion
Irisa/Inria, Campus de Beaulieu, 35042 Rennes cedex, France, Albert.Benveniste@irisa.fr http://www.irisa.fr/sigma2/benveniste/ 2 Verimag, Centre Equation, 2, rue de Vignate, F-38610 Gieres, Paul.Caspi@imag.fr http://www.imag.fr/VERIMAG/PEOPLE/Paul.Caspi 3 U.C. Berkeley, Berkeley, CA 94720, {lcarloni,alberto}@ /HomePages/{lcarloni,alberto}
1
Introduction
The notion of time has been a crucial aspect of electronic system design for years. Dealing with concurrency, time and causality has become increasingly difficult as the complexity of the design grows. The synchronous programming model has had major successes at the specification level because it provides a simpler way to access the power of concurrency in functional specification. Synchronous Languages like Esterel [8], Lustre [14], and Signal [19], the Statecharts modeling methodology [15], and design environments like Simulink/Stateflow [23] all benefit from the simplicity of the synchronous assumption, i.e.: (1) the system evolves through an infinite sequence of successive atomic reactions indexed by a global logical clock, (2) during a reaction each component computes new events for all its output signals based on the presence/absence of events computed in the previous reaction and, (3) the communication of events among components occur instantaneously between two successive reactions. However, if the synchronous assumption simplifies system specification, the problem of deriving a correct physical implementation from it does remain. In