Ch0302
Histone Methylation by PRC2 Is Inhibited by Active Chromatin Marks
Molecular CellArticleHistone Methylation by PRC2Is Inhibitedby Active Chromatin MarksFrank W.Schmitges,1,6Archana B.Prusty,2,6Mahamadou Faty,1Alexandra Stu¨tzer,3Gondichatnahalli M.Lingaraju,1 Jonathan Aiwazian,1Ragna Sack,1Daniel Hess,1Ling Li,4Shaolian Zhou,4Richard D.Bunker,1Urs Wirth,5Tewis Bouwmeester,5Andreas Bauer,5Nga Ly-Hartig,2Kehao Zhao,4Homan Chan,4Justin Gu,4Heinz Gut,1 Wolfgang Fischle,3Ju¨rg Mu¨ller,2,7,*and Nicolas H.Thoma¨1,*1Friedrich Miescher Institute for Biomedical Research,Maulbeerstrasse66,CH-4058Basel,Switzerland2Genome Biology Unit,EMBL Heidelberg,Meyerhofstrasse1,D-69117Heidelberg,Germany3Laboratory of Chromatin Biochemistry,Max Planck Institute for Biophysical Chemistry,Am Fassberg11,D-37077Go¨ttingen,Germany4China Novartis Institutes for Biomedical Research,Lane898Halei Road,Zhangjiang,Shanghai,China5Novartis Institutes for Biomedical Research,CH-4002Basel,Switzerland6These authors contributed equally to this work7Present address:Max Planck Institute of Biochemistry,Am Klopferspitz18,D-82152Martinsried,Germany*Correspondence:muellerj@biochem.mpg.de(J.M.),nicolas.thoma@fmi.ch(N.H.T.)DOI10.1016/j.molcel.2011.03.025SUMMARYThe Polycomb repressive complex2(PRC2)confers transcriptional repression through histone H3lysine 27trimethylation(H3K27me3).Here,we examined how PRC2is modulated by histone modifications associated with transcriptionally active chromatin. We provide the molecular basis of histone H3 N terminus recognition by the PRC2Nurf55-Su(z)12 submodule.Binding of H3is lost if lysine4in H3is trimethylated.Wefind that H3K4me3inhibits PRC2 activity in an allosteric fashion assisted by the Su(z)12C terminus.In addition to H3K4me3,PRC2 is inhibited by H3K36me2/3(i.e.,both H3K36me2 and H3K36me3).Direct PRC2inhibition by H3K4me3and H3K36me2/3active marks is con-served in humans,mouse,andfly,rendering tran-scriptionally active chromatin refractory to PRC2 H3K27trimethylation.While inhibition is present in plant PRC2,it can be modulated through exchange of the Su(z)12subunit.Inhibition by active chromatin marks,coupled to stimulation by transcriptionally repressive H3K27me3,enables PRC2to autono-mously template repressive H3K27me3without over-writing active chromatin domains.INTRODUCTIONPolycomb(PcG)and trithorax group(trxG)proteins form distinct multiprotein complexes that modify chromatin.These com-plexes are conserved in animals and plants and are required to maintain spatially restricted transcription of HOX and other cell fate determination genes(Henderson and Dean,2004; Pietersen and van Lohuizen,2008;Schuettengruber et al., 2007;Schwartz and Pirrotta,2007).PcG proteins act to repress their target genes while trxG protein complexes are required to keep the same genes active in cells where they must be expressed.Among the PcG protein complexes,Polycomb repressive complex2(PRC2)is a histone methyl-transferase(HMTase) that methylates Lys27of H3(H3K27)(Cao et al.,2002;Czermin et al.,2002;Kuzmichev et al.,2004;Mu¨ller et al.,2002).High levels of H3K27trimethylation(H3K27me3)in the coding region generally correlate with transcription repression(Cao et al., 2008;Nekrasov et al.,2007;Sarma et al.,2008).PRC2contains four core subunits:Enhancer of zeste[E(z),EZH2in mammals], Suppressor of zeste12[Su(z)12,SUZ12in mammals],Extra-sex combs[ESC,EED in mammals]and Nurf55[Rbbp4/ RbAp48and Rbbp7/RbAp46in mammals](reviewed in Schuet-tengruber et al.,2007;Wu et al.,2009).E(z)is the catalytic subunit;it requires Nurf55and Su(z)12for nucleosome associa-tion,whereas ESC is required to boost the catalytic activity of E(z)(Nekrasov et al.,2005).Recent studies reported that ESC binds to H3K27me3and that this interaction stimulates the HMTase activity of the complex(Hansen et al.,2008;Margueron et al.,2009;Xu et al.,2010).The observation that PRC2is able to bind to the same modification that it deposits led to a model for propagation of H3K27me3during replication.In this model, recognition of H3K27me3on previously modified nucleosomes promotes methylation of neighboring nucleosomes that contain newly incorporated unmodified histone H3(Hansen et al.,2008; Margueron et al.,2009).However,it is unclear how such a positive feedback loop ensures that H3K27trimethylation remains localized to repressed target genes and does not invade the chromatin of nearby active genes.In organisms ranging from yeast to humans,chromatin of actively transcribed genes is marked by H3K4me3, H3K36me2,and H3K36me3modifications:while H3K4me3is tightly localized at and immediately downstream of the transcrip-tion start site,H3K36me2peaks adjacently in the50coding region and H3K36me3is specifically enriched in the30coding region(Bell et al.,2008;Santos-Rosa et al.,2002).Among the trxG proteins that keep PcG target genes active are the HMTases Trx and Ash1,which methylate H3K4and H3K36, respectively(Milne et al.,2002;Nakamura et al.,2002;Tanaka330Molecular Cell42,330–341,May6,2011ª2011Elsevier Inc.et al.,2007).Studies in Drosophila showed that Trx and Ash1 play a critical role in antagonizing H3K27trimethylation by PRC2,suggesting a crosstalk between repressive and activating marks(Papp and Mu¨ller,2006;Srinivasan et al.,2008).In this study we investigated how PRC2activity is modulated by chromatin marks typically associated with active transcrip-tion.We found that the Nurf55WD40propeller binds the N terminus of unmodified histone H3and that H3K4me3 prevents this binding.In the context of the tetrameric PRC2 complex,wefind that H3K4me3and H3K36me2/3(i.e.,both H3-K36me2and H3-K36me3)inhibit histone methylation by PRC2in vitro.Dissection of this process by usingfly,human, and plant PRC2complexes suggests that the Su(z)12subunit is important for mediating this inhibition.PRC2thus not only contains the enzymatic activity for H3K27methylation and a recognition site for binding to this modification,but it also harbors a control module that triggers inhibition of this activity to prevent deposition of H3K27trimethylation on transcription-ally active genes.PRC2can thus integrate information provided by pre-existing histone modifications to accurately tune its enzymatic activity within a particular chromatin context.RESULTSStructure of Nurf55Bound to the N Terminusof Histone H3Previous studies reported that Nurf55alone is able to bind to histone H3(Beisel et al.,2002;Hansen et al.,2008;Song et al., 2008;Wysocka et al.,2006)but not to a GST-H3fusion protein (Verreault et al.,1998).By usingfluorescence polarization(FP) measurements,we found that Nurf55binds the very N terminus of unmodified histone H3encompassing residues1–15(H31–15) with a K D of$0.8±0.1m M but does not bind to a histone H319–38 peptide(Figure1A).Crystallographic screening resulted in the successful cocrystallization of Nurf55in complex with an H31–19peptide.After molecular replacement with the known structure of Nurf55(Song et al.,2008),the initial mF oÀDF c differ-ence map showed density for H3residues1–14in bothNurf55molecules in the crystallographic asymmetric unit. Figures1B–1E show the structure of H31–19bound to Drosophila Nurf55,refined to2.7A˚resolution(R/R free=20.1%and25.0%, Table1;Figure S1A,available online).The H3peptide binds to theflat surface of the Nurf55WD40propeller(Figure1B),subse-quently referred to as the canonical binding site(c-site)(Gaudet et al.,1996).The H3peptide is held in an acidic pocket(Figures 1C and1E)and traverses the central WD40cavity in a straight line across the propeller(Figure1B).Nurf55binds the H3peptide by contacting H3residues Ala1, Arg2,Lys4,Ala7,and Lys9.Each of these residues forms side-chain specific contacts with the Nurf55propeller(Figures 1D and1E).The bulk of the molecular recognition is directed toward H3Arg2and Lys4.Ala1sits in a buried pocket with its a-amino group hydrogen bonding to Nurf55Asp252,which recognizes andfixes the very N terminus of histone H3.The neighboring Arg2is buried deeper within the WD40propeller fold,with its guanidinium group sandwiched by Nurf55residues Phe325and Tyr185(Figure1D).H3Lys4binds to a well-defined surface pocket on Nurf55located on blade2,near the central cavity of the propeller.Its3-amino group is specifically coordi-nated by the carboxyl groups of Nurf55residues Glu183andGlu130and through the amide oxygen of Asn132(Figure1E).Lys9is stabilized by hydrophobic interactions on the WD40surface while having its3-amino group held in solvent-exposedfashion(Figure1D).Ser10of histone H3marks the beginningof a turn that inverses the peptide directionality.Histone H3residues Thr11–Lys14become progressively disordered andare no longer specifically recognized.No interpretable densitywas observed beyond Lys14.Taken together,Nurf55specificallyrecognizes an extended region of the extreme N terminus ofhistone H3(11residues long,700A˚2buried surface area)in thecanonical ligand binding location of WD40propeller domains. Structure of the Nurf55-Su(z)12Subcomplex of PRC2 The H3-Nurf55structure prompted us to investigate how Nurf55might bind histone tails in the presence of Su(z)12,its interactionpartner in PRC2(Nekrasov et al.,2005;Pasini et al.,2004).Asafirst step we mapped the Nurf55-Su(z)12interaction in detailby carrying out limited proteolysis experiments on reconstitutedDrosophila PRC2,followed by isolation of a Nurf55-Su(z)12subcomplex.Mass spectrometric analysis and pull-down exper-iments with recombinant protein identified Su(z)12residues73–143[hereafter referred to as Su(z)1273–143]as sufficient forNurf55binding(Figures S1C and S1D).Crystals were obtained when Drosophila Nurf55and Su(z)12residues64–359were set up in the presence of0.01%subtilisinprotease(Dong et al.,2007).After data collection,the structurewas refined to a maximal resolution of2.3A˚(Table1).Molecularreplacement with Nurf55as search model provided clear initialmF oÀDF c difference density for a13amino acid-long Su(z)12 fragment spanning Su(z)12residues79–91(Figures2A–2C).Thefinal model was refined to2.3A˚(R/R free=17.5%/20.9%)and verified by simulated annealing composite-omit maps(Fig-ure S1B).The portion of Su(z)12involved in Nurf55binding willhenceforth be referred to as the Nurf55binding epitope(NBE).The Su(z)12binding site on Nurf55is located on the side of thepropeller between the stem of the N-terminal a helix(a1)andthe PP loop(Figures2A and2B).Binding between Su(z)12andNurf55occurs mostly through hydrophobic interactions in anextended conformation.The interaction surface betweenNurf55and the NBE is large for a peptide,spanning around800A˚2.Sequence alignment between Su(z)12orthologs revealsthat the NBE is highly conserved(53%identity and84%similarity)in animals and in plants(Figure2E).With the exceptionof Su(z)12Arg85,the majority of the conserved Su(z)12NBEresidues engage in hydrophobic packing with Nurf55(Figures2B and2C).Together with the Su(z)12VEFS domain and theC2H2zincfinger(C5domain)(Birve et al.,2001),the NBE consti-tutes the only identifiable motif in Su(z)12found conserved in allSu(z)12orthologs.The NBE binding site on Nurf55has previously been shown tobe occupied by helix1of histone H4(Figure2D)(Murzina et al.,2008;Song et al.,2008),an epitope not accessible in assemblednucleosomes(Luger et al.,1997).Nurf55binds H4and theSu(z)12NBE epitope in a different mode,and importantly,withopposite directionality(Figure2D).The detailed comparison ofthe Nurf55-Su(z)12structure with that of H4bound to Nurf55Molecular CellAllosteric PRC2Inhibition by H3K4me3/H3K36me3Molecular Cell42,330–341,May6,2011ª2011Elsevier Inc.331strongly suggests that binding of Su(z)12(NBE)and of H4(helix 1)are mutually exclusive (Figure 2D).We therefore refer to the Su(z)12and H4binding site on Nurf55as the S/H -site.Su(z)12fragments that include the NBE have poor solubility by themselves and generally require Nurf55coexpression for solu-bilization.However,we were able to measure binding of a chem-ically synthesized Su(z)1275–93peptide to Nurf55by isothermal titration calorimetry (ITC)and found that the peptide was bound with a K D value of 6.7±0.3m M in a 1:1stoichiometry (Fig-ure 2F).Pull-down experiments with recombinant proteinandFigure 1.Crystal Structure of Nurf55in Complex with a Histone H31–19Peptide(A)Nurf55binds to an H31–15peptide with an affinity of $0.8±0.1m M as measured by FP.It has similar affinity for an H31–31peptide (2.2±0.2m M)but no binding can be detected to an H319–38peptide.(B)Ribbon representation of Nurf55-H31–19.Nurf55is shown in rainbow colors and H31–19is depicted in green.The peptide is bound to the c -site of the WD40propeller.(C)Electrostatic surface potential representation (À10to 10kT/e)of the c -site with the H3peptide shown as a stick model in green.(D)Close-up of the c -site detailing the interactions between Nurf55(yellow)and the H31–19peptide (green),with a water molecule shown as a red sphere.(E)Schematic representation of interactions between the H31–19peptide (green)and Nurf55(yellow).Molecular CellAllosteric PRC2Inhibition by H3K4me3/H3K36me3332Molecular Cell 42,330–341,May 6,2011ª2011Elsevier Inc.streptavidin beads suggest that Su(z)12residues 94–143harbor an additional Nurf55binding site not visible in the structure (Figure S1E).Su(z)12144–359,lacking the N-terminal 143residues,no longer binds to Nurf55.The NBE (residues 79–93)and the region adjacent to the NBE (residues 94–143)are thus required for stable interaction with Nurf55.The extended NBE was found enriched after limited proteolysis and in subsequent gel filtration runs coupled with quantitative mass spectrometry (Figure S1C).As the NBE was the only fragment visible after structure determi-nation,we conclude that it represents the major Su(z)12interac-tion epitope for Nurf55binding.The Nurf55-Su(z)12Complex Binds to Histone H3In order to study the potential interdependence of the identified Nurf55binding sites we compared binding of Nurf55and Nurf55-Su(z)12to the histone H3N terminus.FP experiments showed similar affinities for binding of a histone H31–15peptide to Nurf55(K D $0.8±0.1m M;Figure 1A)and a Nurf55-Su(z)1273–143complex (K D $0.6±0.1m M;Figure 2G).Importantly,mutation of Nurf55resi-dues contacting H3via its c -site drastically reduced binding to an H31–15peptide (Figure S2A),demonstrating that the Nurf55-Su(z)1273–143complex indeed binds the H31–15peptide through the c -site.We conclude that the presence of Su(z)12is compatible with Nurf55binding to H3via its c -site and that the two binding interactions are not interdependent.The observation that the Su(z)12NBE occupies the same Nurf55pocket that was previously shown to bind to helix 1of histone H4prompted us to test whether the Su(z)1273–143-Nurf55complex could still bind to histone H4.We performed pull-down experiments with a glutathione S-transferase (GST)fusion protein containing histone H41–48(Murzina et al.,2008)and found that H4stably interacted with isolated Nurf55but not with Su(z)1273–143-Nurf55(Figure 2H).In PRC2,the presence of Su(z)12in the Nurf55S/H -site therefore precludes binding to helix 1of histone H4.H3Binding by Nurf55-Su(z)12Is Sensitive to the Methylation Status of Lysine 4We next investigated how posttranslational modifications of the H3tail affect binding to the Nurf55-Su(z)1273–143complex.Modi-fications on H3Arg2,Lys9,and Lys14did not change affinity of Nurf55-Su(z)12for the modified H31–15peptide (Figures S2B and S2D).In contrast,peptides that were mono-,di-,or trimethylated on Lys4were bound with significantly reduced affinity exhibiting K D values of 17±3m M (H3K4me1),24±3m M (H3K4me2),and >70m M (H3K4me3),respectively (Figure 2I).The FP binding data were independently confirmed by ITC measurements (Figures S2C–S2F).Together,these findings are in accord with the structural data,which show that H3K9and H3K14are being held with their 3-amino moiety solvent-exposed,while the H3K4side chain is tightly coordinated (Figure 1E).The additional methyl groups on the H3K43-amino group are expected to progressively decrease affinity because of increased steric clashes within the H3K4binding pocket.H3K27Methylation by PRC2Is Inhibited by Histone H3K4me3MarksWe then examined the effect of H3K4me3modifications,which are no longer retained by Nurf55-Su(z)12,on the catalytic activity of PRC2.In a first set of experiments,we determined PRC2steady-state parameters on histone H31–45peptide substrates that were either unmodified or methylated at Lys 4.We observed similar K M values for H3and H3K4me3peptides of 0.84±0.21m M and 0.36±0.07m M,respectively (Figure 3A),and similar K M values for SAM (5.42±0.65m M for H3and 10.04±1.56m M for H3K4me3).The turnover rate constant k cat ,however,was 8-fold reduced in the presence of H3K4me3:2.53±0.21min -1for unmodified H3and 0.32±0.08min -1in the presence of H3K4me3(Figure 3A).While substrate binding is largely unaf-fected,turnover is thus severely inhibited in the presence of H3K4me3.This behavior,which results in a k cat /K M specificity constant of 7.83103M -1s -1(unmodified H3)compared to 0.533103M -1s -1(H3K4me3),is consistent with heterotrophic allosteric inhibition of the PRC2HMTase triggered by the pres-ence of the H3K4me3.To investigate the effect of the H3K4me3modification on PRC2activity in the context of nucleosomes,we reconstituted mononucleosomes with a trimethyllysine analog (MLA)at Lys4in H3(referred to as H3Kc4me3;Figure S3A)(Simon et al.,2007).We found that total H3K27methylation (measured by incorporation of 14C-labeled methyl groups)was substantially impaired on H3Kc4me3-containing nucleosomes compared to wild-type nucleosomes (Figures S3B and S3C).We used western blot analysis to monitor how levels of H3K27mono-,di-,and trimethylation were affected by the H3Kc4me3modifica-tion.While H3K27me1formation was reduced by more than 50%on H3Kc4me3nucleosomes compared to unmodified nucleosomes (Figures 3B and 3C),H3K27dimethylationandTable 1.Crystallographic Data and Refinement StatisticsNurf55–Su(z)12Nurf55–H31–19Space Group P212121P212121theses.Molecular CellAllosteric PRC2Inhibition by H3K4me3/H3K36me3Molecular Cell 42,330–341,May 6,2011ª2011Elsevier Inc.333titrant H3:S/H-siteN CNCSu(z)12 79-91Histone H4 31-41PP-loophelix α10.00.51.0 1.52.0 2.5-16.00-14.00-12.00-10.00-8.00-6.00-4.00-2.000.00-2.00-1.50-1.00-0.500.00020406080100120Time (min)µc a l /s e cMolar RatioK C a l /M o l e o f I n j e c t a n tK D = 6.7 ± 0.3 µMtitrant: H31-15DEFGH ICA B protein concentration [µM]Nurf55-Su(z)12protein concentration [µM]00.20.40.60.81.000.20.40.60.81.00.010.11101000.010.1110100Nurf55Nurf55-Su(z)12unmod K4me1K4me2K4me3f r a c t i o n b o u n df r a c t i o n b o u n d G ST -H 41-48 + N u r f 55G S T -H 41-48 + N u r f 55-S u (z )1273-143N u r f 55(m o c k c o n t r o l )N u r f 55-S u (z )1273-143(m o c k c o n t r o l )Nurf55GST-H41-48Su(z)1273-143i np ut i n p u t i n p u t i n p u t G S T -p u l l d o w n G S T -p u l l d o w n G S T -p u l l d o w n G S T -p u l l d o w n Figure 2.Crystal Structure and Characterization of Nurf55in Complex with the Su(z)12Binding Epitope for Nurf55(A)Ribbon representation of Nurf55-Su(z)12.Nurf55(rainbow colors)depicts the WD40domain nomenclature and Su(z)12is shown in magenta.The S/H -site is marked by a dashed box.(B)Detailed interactions of Su(z)12(magenta)with the S/H -site (yellow).Water molecules are depicted as red spheres.(C)Schematic representation of interactions between Su(z)12(magenta)and Nurf55(yellow).(D)Overlay of the backbone trace of Su(z)12(magenta)and the H4helix a 1(orange)(Song et al.,2008)in the S/H -site.(E)Alignment of the Su(z)12NBE with sequences from Drosophila melanogaster (dm,Q9NJG9),mouse (mm,NP_954666),human (hs,AAH15704),Xenopus tropicalis (xt,BC121323),zebrafish (dr,BC078293),and the three Arabidopsis thaliana (at)homologs Fis2(ABB84250),EMF2(NP_199936),and VRN2(NP_567517).Identical residues are highlighted in yellow.(F)ITC profile for binding of a Su(z)1275–93peptide to Nurf55.Data were fitted to a one-site model with stoichiometry of 1:1.The derived K D value is 6.7±0.3m M.(G)Binding of H31–15to Nurf55(0.8±0.1m M)and Nurf55-Su(z)1273–143(0.6±0.1m M)measured by FP.Molecular CellAllosteric PRC2Inhibition by H3K4me3/H3K36me3334Molecular Cell 42,330–341,May 6,2011ª2011Elsevier Inc.trimethylation were impaired by more than 80%by using H3Kc4me3nucleosomes (Figure 3C).In order to ascertain that inhibition of PRC2is indeed due to trimethylation of the aminogroup in the lysine side chain,and not due to the use of the MLA,we performed HMTase assays on H3K4me3-containing nucleosomes generated by native peptide ligation (Shogren-Knaak et al.,2003)and on H3Kc4me0and H3K4A nucleosomes.H3K27mono-,di-,and trimethylation was comparably inhibited on H3K4me3and on H3Kc4me3-containing nucleosomes,but was not affected by H3Kc4me0and H3K4A (Figures S3D and S3E).We conclude that H3K4me3specifically inhibits PRC2-mediated H3K27methylation with the most pronounced inhibi-tory effects observed for H3K27di-and trimethylation.We next tested whether the H3K4me3modification affects PRC2nucleosome binding.In electrophoretic mobility shift assays (EMSA),we found that PRC2binds unmodified or H3Kc4me3-modified nucleosomes with comparable affinity (Fig-ure S4A).Even though binding of Nurf55to the N terminus of ABC571141712290286571141712290286unmodified H3Kc4me3H3K27me3H4dmPRC2 [nM]H3K27me2H4H3K27me1H4H3K27me1H3K27me3H3K27me2dmPRC2 + unmod H3dmPRC2 + H3Kc4me3r e l a t i v e H M T a s e a c t i v i t ySubstrate Apparent Km of SAM (µM)Apparent Km of peptide (nM)k cat (min )-1k cat /Km (M S )-1-1H31-45 -biotin H3K4me31-45 -biotin5.42 ± 0.6510.04 ± 1.56355 ± 74.60.32 ± 0.080.53 x 10836 ± 207 2.53 ± 0.217.8 x 1033Figure 3.HMTase Activity of PRC2Is In-hibited by H3K4me3Marks(A)HMTase assay with PRC2and H31–45-biotin peptides measuring the concentration of SAH produced by the enzymatic reaction.When an H3K4me3-modified peptide is used,the specificity constant (k cat /K M )is drastically reduced,indicative of heterotrophic allosteric inhibition.(B)Western blot-based HMTase assay by using recombinant Drosophila mononucleosomes (571nM)and increasing amounts of PRC2.HMTase activity was monitored with antibodies against H3K27me1,H3K27me2,or H3K27me3as indicated;in each case the membrane was also probed with an antibody against unmodified histone H4to control for equal loading and western blot processing.Deposition of K27di-and trime-thylation is drastically reduced when nucleosomes are used that carry a H3Kc4me3modification.(C)Quantification of HMTase activity of Drosophila PRC2(286nM)on unmodified and H3Kc4me3-modified nucleosomes by quantitative western blotting.histone H3is almost 100-fold reduced byH3K4me3(Figure 2I and Figure S2F),inter-action of the Nurf55c -site with H3K4does not seem to make a detectable con-tribution to nucleosome binding by PRC2in this assay.Consistent with the allosteric mechanism of H3K4me3inhibition that we had observed in the peptide assays (Figure 3A),inhibition of the PRC2HMTase activity by H3K4me3-containingnucleosomes is not caused by impaired nucleosome binding,but is rather the consequence of reduced catalytic turnover.H3K4me3Needs to Be Present on the Same Tail as K27to Inhibit PRC2We then assessed whether inhibition of the PRC2HMTase activity by H3K4me3requires the K4me3mark to be located on the substrate nucleosome (in cis ),or whether it could also be trig-gered if the H3K4me3modification was provided on a separate peptide (in trans ).We performed HMTase assays on unmodified oligonucleosomes in the presence of increasing amounts of a histone H31–15peptide trimethylated at K4(H31–15-K4me3)(Figure 4A).Addition of the H31–15-K4me3peptide did not affect PRC2HMTase activity at peptide concentrations as high as $200m M.When testing H31–19-unmodified peptide in controls at comparable concentrations,we did observe concentration-dependent PRC2inhibition (Figure 4A),probably because of substrate competition at large peptide excess.As H3K4me3-(H)GST pull-down assay with recombinant GST-H41–48and Nurf55and Nurf55-Su(z)1273–143proteins.GST-H41–48is able to bind Nurf55alone but in the Nurf55-Su(z)1273–143complex the binding site is occupied by Su(z)12(left panel).Control pull-downs with GST beads and either Nurf55or Nurf55-Su(z)1273–143alone showed no unspecific binding (right panel).(I)Binding of different H31–15peptides to Nurf55-Su(z)1273–143measured by FP.While unmodified H3is bound with 0.8±0.1m M affinity,methylation of Lys 4drastically reduces binding affinity (17±3m M for K4me1,24±3m M for K4me2,and >70m M for K4me3).Molecular CellAllosteric PRC2Inhibition by H3K4me3/H3K36me3Molecular Cell 42,330–341,May 6,2011ª2011Elsevier Inc.335modified peptides did not show this competitive behavior,we conclude that PRC2is not inhibited by H3K4me3in trans and that H3K4me3and unmodified H3peptides are probably bound to PRC2in a different fashion.Analogously,we saw no inhibition when testing the effect of H3K4me3in trans by using peptides as substrates (Figure S4B ).Taken together,our findings strongly argue that H3K4me3only inhibits PRC2if present on the same tail that contains the H3K27target lysine (in cis ).Previous studies reported that addition of H3K27me3peptides in trans enhances H3K27methylation of oligonucleosomes by human PRC2through binding to the EED WD40domain (Margueron et al.,2009;Xu et al.,2010).We tested whether addition of H3K27me3peptides in trans would stimulate H3K27methylation by PRC2on H3Kc4me3-modified nucleosomes.We observed that the inhibitory effect of H3Kc4me3-containing nucleosomes can,at least in part,be overcome through addition of high concentrations of H3K27me3peptides (Figure 4B and Figure S4C).PRC2is therefore able to simultaneously integrate inhibitory (H3K4me3)and activating (H3K27me3)chromatin signatures and adjust its enzymatic activity in response to the surrounding epigenetic environment.PRC2Inhibition of H3K4me3Is Conserved in Mammalian PRC2Our results with Drosophila PRC2prompted us to investigate to what extent inhibition by H3K4me3is an evolutionarily conserved mechanism.H3K27methylation by human and mouse PRC2on nucleosome substrates carrying H3Kc4me3modifications was also strongly inhibited,comparable to the inhibition observed for Drosophila PRC2(Figure 5A and Figure S5A).The Su(z)12Subunit Codetermines Whether PRC2Is Inhibited by H3K4me3In Arabidopsis thaliana ,three different E(z)homologs combined with three Su(z)12homologs have been described.The distinct PRC2complexes in plants harboring the different E(z)or Su(z)12subunits are implicated in the control of distinct developmental processes during Arabidopsis development (He,2009).In this study we focused on PRC2complexes con-taining the E(z)homolog CURLY LEAF (CLF).We expressed and reconstituted the Arabidopsis PRC2complex comprising CLF,FERTILIZATION INDEPENDENT ENDOSPERM (FIE,a homolog of ESC),EMBRYONIC FLOWER 2(EMF2,a homolog of Su(z)12),and MULTICOPY SUPPRESSOR OF IRA (MSI1,a homolog of Nurf55).We found that CLF indeed functions as a H3K27me3HMTase (Figure 5B).Moreover,H3K27methylation by the CLF-FIE-EMF2-MSI1complex on nucleosome arrays containing H3Kc4me3was inhibited (Figure 5B)in a manner comparable to human or Drosophila PRC2.We next tested a related Arabidopsis PRC2complex again composed of CLF,FIE,and MSI1but containing the Su(z)12homolog vernalization 2(VRN2)instead of EMF2.The VRN2protein is specifically implicated as a repressor of the FLC locus,thereby controlling flowering time in response to vernalization (reviewed in Henderson and Dean,2004).The CLF-FIE-MSI1-VRN2complex was active on unmodified nucleosomes but,strikingly,it was not inhibited on H3Kc4me3-modified nucle-osomes (Figure 5C).Substitution of a single subunit (i.e.,EMF2by VRN2)thus renders the complex nonresponsive to the H3K4methylation state.While PRC2inhibition by H3K4me3appears hardwired in mammals and flies,in which only a single-Su(z)12ortholog is present,Arabidopsis inhibition can be enabled or disabled through exchange of the Su(z)12homolog.The Su(z)12C Terminus Harboring the VEFS Domain Is the Minimal Su(z)12Domain Required for Activation and Active Mark InhibitionThe importance of the Su(z)12subunit in active mark H3K4me3inhibition prompted us to map the Su(z)12domains required for inhibition.Previous findings showed that E(z)or E(z)-ESC in the absence of Su(z)12is enzymatically inactive (Nekrasov et al.,2005).Moreover,the VEFS domain (Birve et al.,2001)was found to be the major E(z)binding domain (Ketel et al.,2005).We reconstituted mouse PRC2complexes containing EZH2,EED,and either SUZ12C 2H 2domain +VEFS (residues 439–741)or SUZ12VEFS alone (residues 552–741).Both of these minimal complexes were active in HMTase assays on nucleosomes (Figure 5D)but with lower activity than that of the full PRC2complex.We therefore focused on formation ofAB26511030206H3K27me3H4peptides in trans[µM]H3K27me2H4H3K27me1H4H3 unmod H3K4me3H3K36me326511032062651103206n o e n z ym e26511030H3K27me3H4peptides in trans[µM]H3K27me2H4H3K27me1H4H3K27me3n oe n z y m eFigure 4.PRC2Activity Is Not Inhibited by H3K4me3Peptides in trans(A)Western blot-based HMTase assay by using unmodified 4-mer oligonu-cleosomes (36nM)and increasing amounts of H3peptides added in trans .Enzyme concentration was kept constant at 86nM.Western blots were pro-cessed as described in Figure 3B.HMTase activity is inhibited by an unmodified H31–19peptide (left),but not by H3K4me3-or H3K36me3-modified peptides.(B)HMTase assay with H3Kc4me3-modified oligonucleosomes (36nM),86nM PRC2,and H3K27me3peptide in trans .Western blots were processed as described in Figure 3B.HMTase activity of PRC2can be stimulated by the H3K27me3peptide even on inhibiting substrate leading to increased levels of H3K27di-and trimethylation.Molecular CellAllosteric PRC2Inhibition by H3K4me3/H3K36me3336Molecular Cell 42,330–341,May 6,2011ª2011Elsevier Inc.。
MATLAB数值运算
四川师范大学数学与软件科学学院
3.2 插值和拟合
2、拟合
❖ 线性最小二乘拟合
polyfit
❖ 非线性最小二乘拟合
lsqcurvefit
四川师范大学数学与软件科学学院
3.2 插值和拟合
2、拟合
❖ 多项式拟合函数polyfit
p = polyfit(x,y,n)
❖ 常微分方程的数值解的思路
对求解区间进行剖分,然后对微分方程离散成在节点上
的近似公式或近似方程,最后结合给定条件求出近似解。
线性方程组的解法
❖ 直接法
通过有限步四则运算求得方程组准确解。主要有矩阵相
除和消去法。
❖ 迭代法
先给定一个解的初始值,然后按一定的法则逐步求出解
的近似值。
四川师范大学数学与软件科学学院
3.4 线性方程组的数值解
1、直接法
❖ 矩阵相除法
对线性方程组AX=B用矩阵除法来完成,即
X=A\B
若A为m × 矩阵,
当m=n且A可逆时,给出唯一解;
当n>m时,矩阵除给出方程的最小二乘解;
当n<同时,矩阵给出方程的最小范数解。
四川师范大学数学与软件科学学院
3.4 线性方程组的数值解
1、直接法
❖ 消去法
方程的个数和未知数的个不])化简为简化阶梯形,若系数矩阵的秩不等于
增广矩阵的秩,则方程组无解;若两者的秩相等,则方
在某海域测得一些点(x,y)处的水深z由下表给出,
船的吃水深度为5英尺,在矩形区域(75,200)
×(-50,150)里的哪些地方船要避免进入?
x
y
z
129 140 103.5 88 185.5 195
选修五 0302 醛(整理)
P52 在有机化学反应里,通常还可以从加氢 ( 2)
或去氢来分析氧化还原反应,即加氢就是还原 反应去氢就是氧化反应。
作
业
1、《同步学案》P57 2、《基础训练》 P68 1-10删2、8题
随堂检测
1、下列有机物中氧化产物不能发生银镜反应的是(
B
)
A CH3OH B CH3CHOHCH3 C CH3CH2CH2OH D (CH3)3CCH2OH
此醛完全燃烧时生成5.4g水,通过计算求该醛可能的化
学式。n(Ag)=0.2mol CnH2nO ~ 2Ag
1 0.1 2 0.2
n(H2O)=0.3mol n( H)=0.6mol 该醛若饱和则化学式为:C3H6O
该醛若不饱和则化学式为:C4H6O
再见!
△
CH3COONa + Cu2O↓ + 3H2O
(红色) 氧化亚铜
注意: 1、碱必须过量 2、加热至沸腾
应用:检验醛基、糖尿病的检验方法!
5、醛可使溴水和酸性KMnO4溶液褪色
练
一
练
某学生做乙醛的还原实验,取1mol/L的
CuSO4溶液2mL和0.4mol/L的NaOH溶液5mL,在
一个试管中混合加入40%的乙醛溶液加热至沸
腾,无红色沉淀,实验失败的原因是( B )
A、乙醛溶液太少 C、硫酸铜不够 B、氢氧化钠太少 D、加热时间不够
醛的性质的小结:
结论:乙醛既有氧化性又有还原性,但氧化性较弱, 还原性较强。 1、还原反应(加成反应) (1)催化氧化 (2)银镜反应
2、氧化反应
(3)与新制的Cu(OH)2反应 (4)使酸性高锰酸钾溶液、溴水褪色 (5)燃烧
催化剂
HoYbglassceramic
Upconversion luminescence of Ho 3+sensitized by Yb 3+in transparent glass ceramic embedding BaYF 5nanocrystalsZhifa Shan,Daqin Chen,Yunlong Yu,Ping Huang,Fangyi Weng,Hang Lin,Yuansheng Wang *State Key Laboratory of Structural Chemistry,Fujian Institute of Research on the Structure of Matter,Chinese Academy of Sciences,Graduate University of Chinese Academy of Sciences,Yangqiao West Road 155#,Fuzhou,Fujian 350002,China1.IntroductionIn recent years,the rare earth (RE)doped oxyfluoride glass ceramics have attracted great attention for their merits combined of low phonon energy for fluoride and desirable mechanical and chemical performances for oxide [1–3].This kind of material,generally fabricated through controlled crystallization of the definite fluoride nanophase from the precursor glass by heat-treatment,could improve the luminescence properties by incor-porating abundant RE ions into nanocrystals with no loss in the transparency.The first successful synthesis of glass ceramic with high upconversion (UC)efficiency can date back to (Pb,Cd)F 2system by Wang and Ohwaki [4].Some other glass ceramics,such as those containing CaF 2or YF 3nanocrystals which exhibited better RE ions solid solubility,were reported subsequently [5,6].As an excellent optical host,RE doped BaYF 5crystal exhibits superior UC ability.It was reported that when pumped by a Si-doped GaAs diode the luminescence of the Er 3+-doped BaYF 5is about a factor of 8brighter than that of the Er 3+-doped LaF 3phosphor [7].However,the growth of BaYF 5bulk crystal was proved to be difficult and expensive as well [8].Therefore,developing the substitute of the BaYF 5nanocrystals contained glass ceramic is of scientific and technical significance.It was found in our previous investigations that the oxyfluoride glass ceramic may behave as a desirable candidate for developing BaYF 5bulkmaterial,and the UC luminescence of the glass ceramic containing Er 3+:BaYF 5nanocrystals was rather strong [9].Due to its numerous radiative emission channels in the visible and IR region,Ho 3+has been extensively studied in glasses and crystals [10–13].However,there have been few investigations on Ho 3+UC luminescence in the oxyfluoride glass ceramics so far.In present work,the Yb 3+/Ho 3+co-doped transparent glass ceramics containing BaYF 5nanocrystals were fabricated,and the micro-structure and UC luminescence of Ho 3+sensitized by Yb 3+were studied.Some interesting results were revealed and discussed.2.ExperimentThe Yb 3+/Ho 3+co-doped precursor glasses were prepared with the following nominal composition (in mol%):40.0SiO 2–25.0Al 2O 3–15.0BaCO 3–10.0YF 3–10.0BaF 2–0.5HoF 3–x YbF 3(x =0,1.0,2.0and 3.0respectively).For each batch,about 10g of raw materials was fully mixed and melted in a covered platinum crucible in air atmosphere at 14508C for 1h,and then cast into a brass mold followed by annealing to relinquish the inner stress.The precursor glasses (PG)thus were prepared then heated for 2h at 7008C to form glass ceramics (GC)through crystallization.The actual composition of the as-prepared glass was detected by X-ray photoelectron spectroscopy (XPS)using a VG Scientific ESCA Lab Mark II spectrometer equipped with two ultra-high vacuum 6(UHV)chambers.All the binding energies were referenced to the C 1s peak of the surface adventitious carbon at 284.8eV.To identify the crystallization phase and determine the mean size of the crystallites,X-ray diffraction (XRD)analysis wasMaterials Research Bulletin 45(2010)1017–1020A R T I C L E I N F O Article history:Received 11September 2009Received in revised form 27January 2010Accepted 1April 2010Available online 8April 2010Keywords:A.Optical materials D.Microstructure D.Luminescence D.Optical propertiesA B S T R A C TTransparent SiO 2–Al 2O 3–BaCO 3–YF 3–BaF 2glass ceramics co-doped with Yb 3+/Ho 3+ions were prepared by melt quenching and subsequent heating.X-ray diffraction and transmission electron microscopy observation revealed that BaYF 5nanocrystals incorporated with Yb 3+and Ho 3+were precipitated homogeneously among the oxide glass matrix.Three upconversion emission bands centered at 483nm,545nm and 645nm,corresponding to the 5F 3!5I 8,5S 2,5F 4!5I 8and 5F 5!5I 8transitions of Ho 3+respectively,were detected under 976nm excitation,ascribing to the efficient energy transfer from Yb 3+to Ho 3+.The red emission is prevailing in the precursor glass,while the green one turns to be dominant in the glass ceramic.ß2010Elsevier Ltd.All rights reserved.*Corresponding author.Tel.:+8659183705402;fax:+8659183705402.E-mail address:yswang@ (Y.Wang).Contents lists available at ScienceDirectMaterials Research Bulletinj o u r n a l h o m e p a ge :w w w.e l s e v i e r.c o m /l o c a t e /m a t r e s b u0025-5408/$–see front matter ß2010Elsevier Ltd.All rights reserved.doi:10.1016/j.materresbull.2010.04.004carried out with a powder diffractometer (DMAX2500RIGAKU)using Cu K a radiation (l =0.154nm).The microstructures of the samples were studied using a transmission electron microscope (TEM,JEM-2010)equipped with an energy dispersive X-ray spectroscope (EDS).The upconversion emission spectra were recorded using a Hamamatsu R943-02photomultiplier tube (PMT)and a Spex 1000M monochromator under 976nm Ti sapphire laser excitation.All the measurements were carried out at room temperature.3.Results and discussionThe XPS measured actual composition of the 40.0SiO 2–25.0Al 2O 3–15.0BaCO 3–10.0YF 3–10.0BaF 2–1.0YbF 3–0.5HoF 3glass,together with its nominal composition (in atom%),is presented in Table 1.Noticeably,compared with the nominal ones,the actual contents of Ba,Y,Yb,Ho and F elements are more or less reduced,which is due to the thermal evaporation of the fluoride raw materials during high temperature melting.Fig.1shows the XRD patterns of the Yb 3+/Ho 3+co-doped precursor glass and glass ceramic.There are only two humps for the precursor glass,indicating its amorphous structure.After heat-treatment at 7008C,several intense diffraction peaks ascribed to the tetragonal BaYF 5(JCPDS No.46-0039)appear.Based on the width of the diffraction peaks,the mean size of BaYF 5crystallites was evaluated to be about 16nm by Debye–Scherrer formula.As an example,Fig.2a presents the typical TEM micrograph of the 2.0%Yb 3+/0.5%Ho 3+co-doped sample heat treated at 7008C,demonstrating the homoge-neous distribution of spherical nanocrystals with 15–25nm in size among the glassy matrix,which might be a key factor determining the optical performance of the glass ceramic [14,15].The diffraction rings in the corresponding selected area electron diffraction (SAED)pattern shown in Fig.2b can be well indexed to the pure BaYF 5crystalline phase.The high-resolution TEM (HRTEM)image,as exhibited in Fig.2c,shows the lattice structure of an individual BaYF 5nanocrystal.In the inset of Fig.2c,the Fast Fourier Transform (FFT)pattern taken from the marked squareregion is indexed to a tetragonal BaYF 5crystal along the ½¯11¯1 zone axis.In order to detect the distribution of RE 3+ions in the sample,the EDS spectra with nanosized probe taken from an individual nanocrystal and from the glass matrix respectively were recorded.The spectrum from a nanocrystal,shown in Fig.3a,exhibits Ba,Y,F,Yb,and Ho signals,and the emergence of Al,Si,and O peaks is attributed to the glass matrix surrounding the nanocrystal;while in the spectrum from the glass matrix (Fig.3b),no Yb and Ho signals are detected.The Cu peaks are originated from the copper grid supporting the TEM specimen.This result indicates that Ho 3+Table 1Nominal and actual compositions (atom%)of the glass.Element Nominal Actual Si 11.4012.39Al 14.2513.57Ba 7.12 4.35Y 2.85 2.40O 48.4355.48F 15.5311.45Yb 0.280.23Ho0.140.13Fig.1.XRD patterns of PG (a)and GC (b)samples.Fig.2.(a)TEM micrograph,(b)SAED pattern,and (c)HRTEM image of 2.0%Yb 3+/0.5%Ho 3+co-doped GC;inset in (c)is FFT pattern taken from the marked square region.Z.Shan et al./Materials Research Bulletin 45(2010)1017–10201018and Yb3+ions are mainly concentrated in the BaYF5nanocrystals after crystallization.Typical room temperature UC emission spectra of the Yb3+/Ho3+ co-doped glass ceramics under976nm excitation are presented in Fig.4.There are several optical emission bands centered at483nm, 545nm and645nm originated from5F3!5I8,5S2,5F4!5I8and 5F5!5I8transitions of Ho3+respectively.The visible UC emission is originated from the energy transfer of Yb3+to Ho3+by promoting electrons from the ground state to the diverse excited states of Ho3+[16].The visible emission intensifies significantly with increasing Yb3+content from1.0%to2.0%.However,it turns to be weakened when Yb3+content reaches 3.0%,owing to the concentration quenching of Ho3+.The number of photons involved in the UC process was determined by analyzing the dependence of the upconverted signal intensity(I UP)as function of the pumping intensity(I IR).It is well known that this dependence is expressed by the equation:I UP/ðI IRÞn(1) where n denotes the number of photons absorbed to produce the upconverted emission.The inset in Fig.4presents the log–log plot of the green emission intensity versus the excitation power for the 2.0%Yb3+/0.5%Ho3+co-doped glass ceramic.The value of n is determined to be 1.2,indicating a two photons absorption mechanism for the upconversion emission.The small value of n (much smaller than2)is ascribed to the typical saturation of UC luminescence resulted from the population exhausting in the ground state[17].The proposed UC mechanism is described in the energy diagram shown in Fig.5.The excitation signal(976nm)was initially absorbed by Yb3+ions.Then Yb3+electrons decay non-radiatively by transferring their energy to the nearby Ho3+ions to populate the5I6excited level.The excess of energy between the two levels was dissipated by the vibration of the host lattice.The population in the5I6level is promoted to the5F4,5S2levels either by excited state absorption(ESA)or by energy transfer(ET)from another excited Yb3+ion.Once the5F4and5S2levels are populated,the majority of the excited electrons radiatively relax to the ground state,resulting in the intense green emissions.As for the red emission,there exist two possible energy ways for the population of the5F5emitting level:(1)Yb3+:2F5/2+Ho3+:5I7!Yb3+:2F7/2+Ho3+:5F5where the5I7level is populated through the non-radiative decay of the5I6 level;(2)non-radiative phonon-assisted relaxation from the5F4,5S2excited levels to the5F5level.For the Yb3+/Ho3+co-doped precursor glass,only weak green and red emission bands were observed,with the redemissionFig.4.UC emission spectra of Yb3+/Ho3+co-doped GCs with various Yb3+contentsunder976nm excitation;inset shows the log–log plots of green upconversionemission intensity versus excitationpower.Fig.5.Schematic diagrams illustrating the mechanisms of Yb3+-sensitized Ho3+upconversion luminescence.Z.Shan et al./Materials Research Bulletin45(2010)1017–10201019stronger than the green one,in contrary with the case for the glass ceramic,as shown in Fig.6.It is well known that the undesirable energy dissipation originates mainly from the multi-phonon relaxation of rare earth ions,and the probability of the non-radiative decay decreases exponentially with the increasing of the number of required phonons [18].Since the fluoride has lower phonon energy than the oxide,in the glass ceramic,electrons tend to stay at the metastable 5I 6level and then be excited to 5F 4,5S 2levels through ESA or ET approaches;while in the precursor glass,owing to its high phonon energy of the oxide glass matrix,electrons populated in the 5I 6level can easily relax to the metastable 5I 7level and then be excited to the 5F 5level.4.ConclusionsTransparent oxyfluoride glass ceramics containing Yb 3+/Ho 3+:BaYF 5nanocrystals were prepared by controlled crystalli-zation,and the infrared to visible UC luminescence of the precursor glass and glass ceramic was investigated.The red UC emission is stronger than the green one in the precursor glass.After crystallization,the UC luminescence intensifies remarkably owing to the incorporation of Yb 3+/Ho 3+ions into the BaYF 5nanocrystals,and the green emission turns to be preponderated over the red one.AcknowledgementsThis work was supported by the National Natural Science Foundation of China (10974201and 50902130)and State Key Laboratory of Optoelectronic Materials and Technologies (KF2008-ZD-05).References[1]L.Kassab,F.Bomfim,J.Martinelli,N.Wetter,o,C.de Arau´jo,Appl.Phys.B 94(2009)239.[2]D.Q.Chen,Y.S.Wang,F.Bao,Y.L.Yu,J.Appl.Phys.101(2007)113511.[3]J.Me´ndez-Ramos,M.Abril,I.Martı´n,U.Rodrı´guez-Mendoza,vin,V.Rodri-guez,P.Nu´ez,A.Lozano-Gorrı´n,J.Appl.Phys.99(2006)113510.[4]Y.Wang,J.Ohwaki,Appl.Phys.Lett.63(1993)3268.[5]D.Q.Chen,Y.S.Wang,Y.L.Yu,P.Huang,Appl.Phys.Lett.91(2007)051920.[6]S.Ye,B.Zhu,J.Chen,J.Luo,J.Qiu,Appl.Phys.Lett.92(2008)141112.[7]H.Guggenheim,L.Johnson,Appl.Phys.Lett.15(1969)51.[8]G.S.Yi,W.B.Lee,G.M.Chow,J.Nanosci.Nanotech.7(2007)2790.[9]F.Liu,Y.S.Wang,D.Q.Chen,Y.L.Yu,E.Ma,L.H.Zhou,P.Huang,Mater.Lett.61(2007)5022.[10]E.De la Rosa,P.Salas,H.Desirena,C.Angeles,R.Rodrı´guez,Appl.Phys.Lett.87(2005)241912.[11]A.Kiry´anov,V.Aboites,A.Belovolov,M.Timoshechkin,M.Belovolov,M.Damzen,A.Minassian,Opt.Express.10(2002)832.[12]I.R.Martı´n,V.D.Rodrı´guez,vı´n,U.R.Rodrı´guez-Mendoza,J.Alloys Compd.275(1998)345.[13]L.Feng,J.Wang,Q.Tang,L.Liang,H.Liang,Q.Su,J.Lumin.124(2007)187.[14]hoz,I.Martin,J.Calvilla-Quintero,Appl.Phys.Lett.86(2005)051106.[15]K.Driesen,V.Tikhomirov,C.Grller-Walrand,V.Rodrı´guez,A.Seddon,Appl.Phys.Lett.88(2006)073111.[16]J.Qiu,A.Makishima,Sci.Technol.Adv.Mater.5(2004)313.[17]M.Pollnau,D.R.Gamelin,S.R.Luthi,H.U.Gudel,Phys.Rev.B 61(2000)3337.[18]T.Miyakawa,D.Dexter,Phys.Rev.B 1(1970)2961.Fig.6.UC spectra of 2.0%Yb 3+/0.5%Ho 3+co-doped PG and GC under 976nm excitation;inset shows the magnified UC spectrum of PG.Z.Shan et al./Materials Research Bulletin 45(2010)1017–10201020。
kronos_titanium_dioxide_all_types-dry_pigment_usa
Personal protective equipment General protective and hygienic The usual precautionary measures for handling chemicals should be followed. measures Titanium dioxide pigments are not irritant but as with all fine powders can absorb moisture and natural oil from the surface of the skin during prolonged exposure. Prolonged exposure should be avoided by wearing suitable protective gloves and clothing. Breathing equipment: Use suitable respiratory protective device when high concentrations are present. For example use a NIOSH-approved respirator for particulates with N100, P100, or R100 filter. The respirator must be selected by a technically qualified individual. Use gloves ons to minimize prolonged skin contact and prevent drying and subsequent irritation of skin. Check protective gloves prior to each use for their proper condition. Preventive skin protection by use of skin-protecting agents is recommended. Safety glasses Protective work clothing. (Contd. on page 4)
合成盐酸工艺流程
管道代号对照
一、管道号例如:86056-CA21H-6"-P-IH中86056为管线号,CA21H为管道等级,6"为管道尺寸,P 为管道介质代码,IH绝热类型1、管道等级CA21H中第一个字母为法兰压力等级,第二个字母为管道材料,第三个数字为腐蚀余量,第四个数字为序列号,第五个字母为后缀(特殊要求)(1)、法兰压力等级A:150C:300E:600F:900H:1500J:2500S:BDO合成高压管道特殊等级(2)、管道材料A:碳钢C:碳钢(低温)D:304SS/304LSSE:316SS/316LSSF:321SSP:20合金R:HASTELLOY合金(3)、后缀(特殊要求)C:碱液专用G:镀锌H:氢气专用J:夹套管N:高压蒸汽专用R:衬里管S:强酸专用T:催化剂专用U:地管2、管道介质代码(1) BDO装置P:工艺介质、化学品IA:仪表空气NG:氮气PA:工厂空气FOS:燃料油供给FOR:燃料油返回FG:燃料气LO:润滑油SO:废油CWS:循环上水CWR:循环回水FW:消防水STM:蒸汽LS:低压蒸汽IS:次中压蒸汽MS:中压蒸汽HS:高压蒸汽SPS:SPD用高压蒸汽CN:冷凝液LSC:低压蒸汽凝液ISC:次中压蒸汽凝液MSC:中压蒸汽凝液HSC:高压蒸汽凝液PW:饮用水SW:生产水DW:脱盐水BFW:锅炉给水RW:生活水AB:乙炔排污B:放空气排污CWW:化学污水OWW:含油污水SWW:生活污水SL:浆料OS:含油浆料NOS:无油浆料SSW:地表雨水PS:工艺排污GCS:冷冻上水GCR:冷冻回水RCS:冷冻剂上水RCR:冷冻剂回水(2) 甲醛装置BB:导热油冷凝器排污BFW:锅炉给水DC:导热油(液)DI:去离子水DN:脱盐水+0.054%氢氧化钠DV:导热油(气)FA:新鲜空气FD:甲醛溶液(浓度0-2%)FG:甲醛气(浓度0.1-10%)FM:甲醛溶液(浓度2.1-56%)FW:工业水GL:乙二醇HS:高压蒸汽HC:高压蒸汽凝液LS:低压蒸汽LC:低压蒸汽凝液ME:甲醇NA:25%氢氧化钠NG:天然气OD:废液排放P:工艺液PG:工艺气体PW:工艺水RG:循环气(浓度小于0.1%的甲醛气) RWR:冷冻回水RWS:冷冻上水VG:放空气CH:化学品(3) 乙炔清净ACE:乙炔DOW:生活水IW:工业水LD:清净下水(乙炔凝液)N:氮气PSUA:98%浓硫酸WW:废水WCA:含乙炔水(4) 提氢A:工艺空气BO:排污液HY:氢气VT:放空气SC:蒸汽冷凝液MW:补充水系统PW:生产生活水系统IW:低压给水FW:高压消防水CNS:清净下水系统RD:雨水系统、事故消防水系统3、绝热类型ET:电伴热JS:蒸汽夹套管ST:蒸汽伴热IA:隔音IC:保冷IH:保温IS:人设防护FS:泡沫二、设备位号BA-80:乙炔净化BY-81:BYD合成BS-82:BDO合成BC-83:BDO浓缩+丁醇回收BR-84:BDO精馏Y-86:公用工程P:泵MX:搅拌器R:反应器C:压缩机E:换热器D:贮槽T:贮罐V:塔J:喷射器S:排放池FS:火炬F:过滤器L:起重机/装车鹤管SL:消音器PA:加药系统三、PID02:乙炔清净03:提氢04:甲醛装置05:BDO装置10:空压制氮、冷冻站四、图号解释解释:前两位为工段号,三四位为专业,1、工段00:厂区外管00-**-0500厂区外管00-**-0501:1#管廊00-**-0502:2#管廊00-**-0503:3#管廊00-**-0504:4#管廊02:乙炔装置02-**-0000:乙炔装置02-**-0100:电石储运02-**-0101电石卸车02-**-0102:筒仓02-**-0103:筒仓除尘02-**-0104:破碎楼02-**-0105:1#栈桥02-**-0106:2#栈桥02-**-0107:3#栈桥02-**-0300:乙炔清净02-**-0500:乙炔气柜02-**-2100:乙炔装置管廊03 制氢装置03-**-0100:制氢工序03-**-0900:装置地下管网04:甲醛装置04-**-0100:甲醛框架04-**-0200:甲醛中间罐区04-**-0300:甲醛装置管廊05:BDO装置05-**-0100:乙炔供应+BYD合成05-**-0101:BYD反应框架05-**-0102催化剂厂房05-**-0103催化剂储罐框架05-**-0104板框压滤机厂房05-**-0105乙炔循环压缩机厂房05-**-0106:BYD精馏05-**-0200:BDO合成05-**-0201:合成厂房05-**-0202:压缩厂房05-**-0300:BDO提浓05-**-0301:BDO提浓与精馏框架05-**-0302:丁醇提浓与精馏框架05-**-0400:BDO精馏05-**-0500:中间罐区05-**-0700:BDO装置管廊05-**-0900:乙炔净化05-**-1000:辅助设施+冷冻站09**-0000 公用工程09-**-0100:循环冷却水站09-**-0101:冷却塔09-**-0102:循环水泵房09-**-0200:脱盐水站10-**-0000:辅助设施10-**-0100:冷冻站10-**-0200:空压制氮站10-**-0201:空压制氮厂房10-**-0300:中央控制楼与分析楼10-**-0500:储运设施10-**-0501:成品罐区(液体罐区)10-**-0502:泡沫消防10-**-0503:汽车装车站10-**-0700:生产生活消防水站10-**-0701:综合泵站10-**-0800:回用水处理站10-**-0900:全厂火炬10-**-1000:综合仓库10-**-1100:综合维修10-**-1200:泡沫消防站10-**-1400:换热站10-**-1600:污水收集10-**-1604:污水收集泵房2、专业11:热工15:安全/消防/卫生30:总体31:粉体工程40:化工工艺41:工艺系统42:管道46:管道材料49:分析化验50:自控61:建筑62:结构70:暖通80:给排水/化水90:电气。
植物分类检索表-详细编排【范本模板】
植物界分类检索表姓名:班级:学院:植物界分类检索表及种子植物分科检索表一、植物界分类检索表1。
植物体无根、茎、叶的分化;雌性生殖器官由单细胞构成。
2。
无叶绿素3。
细胞中无细胞核的分化..。
.。
.。
.....。
...。
....。
..。
..。
..。
.。
..1)细菌3. 细胞中有细胞核的分化。
..。
.。
.。
.。
...。
.。
.。
..。
.。
.。
....。
..2)真菌2. 有叶绿素..。
.。
...。
.。
.。
...。
...。
...。
.....。
.。
...。
.。
..。
...。
3)藻类植物1. 植物体有根、茎、叶分化(苔藓除外);雌性生殖器官由多细胞构成。
4。
无维管束。
.。
...。
...。
...。
....。
..。
.。
....。
.。
.。
..。
....。
..。
....。
.4)苔藓植物4. 有维管束5. 无种子...。
.。
.。
..。
.。
.。
.。
....。
.。
..。
..。
....。
...。
.。
..5)蕨类植物5. 有种子6. 种子外面无子房包被...。
..。
..。
....。
...。
....。
.。
..。
.。
.。
.。
..6)裸子植物6. 种子外面有子房包被.。
.。
.。
.。
..。
....。
..。
.。
.。
.。
.。
..7)被子植物二、种子植物分科检索表1. 胚珠裸露,不包于子房内;种子裸露,不包于果实内..。
.。
.裸子植物Gymnospermae2. 花无假花被,胚珠无细长的珠被管.3. 叶羽状深裂,集生于常不分枝的树干顶部或块状茎上。
.。
..。
.。
..。
.苏铁科Cycadaceae3。
叶不为羽状深裂,树干多分枝。
4。
叶扇形,具多数2叉状细脉,叶柄长..。
.。
..。
..。
...。
....。
.。
银杏科Ginkgoaceae4. 叶不为扇形,无柄或有短柄。
5. 雌球花发育成球果;种子无肉质假种皮。
6。
雌雄异株,稀同株,雄蕊具4~20个悬垂的花药,苞鳞腹面仅l粒种子。
..。
.南洋杉科 Arauc afiaceae6。
雌雄同株,稀异株;雄蕊具2~9个背腹面排列的花药,种鳞腹面有1至多粒种子。
项目档案分类编号规则
项目档案分类编号规则一、目的为规范统一中国石油呼和浩特石化公司500万吨/年炼油扩能改造工程(以下简称500万项目)文件的管理与控制,统一项目的文件编号系统,特制定本规定。
二、适用范围本规定适用于500万项目中包括呼和浩特石化公司500万吨/年炼油扩能改造工程项目部(以下简称项目部),工程总承包、设计、施工、监理等承建单位以及供货商需要正式发布及受控文件,均应按照本程序的规定进行编码。
三、项目文件内容项目文件包括项目前期文件、项目竣工文件、项目竣工验收文件。
其中项目竣工文件又包括项目施工文件、项目竣工图和项目监理文件。
四、项目文件编号名词定义(一)项目号中国石油呼和浩特石化公司500万吨/年炼油扩能改造工程项目号定为“P5311”。
(二)部门及专业代码部门/专业代码为3 位代码,见附件1,技术类文件专业代码见附件2。
(三)文件类型码文件类型码为 3 位代码,文件的类型分类及编码定义见附件3。
1(四)装置号装置号为4位代码。
(五)工段号工段号应由设计单位在相关设计文件中明确,工段号应设置为2位数字代码。
(六)单位码项目部应对项目的相关单位进行编码,单位编码为4位代码。
单位码规定见附件5。
五、项目文件编号规定(一)项目前期文件1、可行性研究、任务书。
项目可行性性研究报告批复前的文件编号规定按照计划与控制部相关规定执行。
2、项目基础资料。
项目基础资料可不编号。
3、项目准许类文件。
项目准许类文件可不编号。
(二) 项目管理文件1、项目管理制度文件。
包括项目部针对综合管理、财务、项目管理、质量安全、技术与设计、物资采购、施工管理和项目控制,发布的规定、程序、计划及招投标、各类报告相关文件等,均采用如下编号方式:P5311 , VVVV , XXXX , WWW ,ZZZ序列号(3位)文件类型号(3位)部门/专业代码(4位)装置号(4位)项目号(5位)22、项目沟通文件项目部发布/接受的非技术类文件,主要指项目沟通文件,包括项目部与最终用户、承包商、供货商及第三方之间的信函、传真、文件传送单、备忘录等,编号规则如下:P5311 , VVVV , WWWW/XXXX , YYY ,ZZZ序列号(3位)文件类型号(3位)接受单位码(4位)发送单位码(4位)装置号(4位)项目号(5位)3、会议纪要P5311 ,WWWW ,XXXX , YYY ,ZZZ序列号(3位)文件类型号(3位)单位码(4位)装置号(4位)项目号(5位)4、项目合同文件项目合同编号,由项目部计划控制部统一编号。
有机化学综合复习题及解答
有机化学综合复习题及解答1.写出下列反应的主要产物:OH OH+(1).H SO (CH 43)23CCH 2OH(2).(CH 3)2CC(CH 3)H 2(3).H 2SO 4(4).OHNaBr,H 2SO 4OH(5).OHHBr(6).OHPCC CH 2Cl 2CH 3CH 3(7).PBr HOH 3(8).O ()C MgBr C acetone12H 52H 5CH 3(2)H 3O +CH 3OCHCH CH 2OH(9).(10).CH H 5IO 6CH 33OHCH 3(11).H SO 4(A1)O 3H CH 23B(2)Zn,H 2OOH解答:O(1).(CH 3)2CCHCH 3(2).CH 3CC(CH 3)3(3).Br(4).CH 3(CH 2)3CH 2Br(5).(6).CH 3(CH 2)5CHOCH 3CH 3(7).HBr (8).OH +antiomer C 2H 5C 2H 5CH 3OHH 3C CH 3OO(9).(10).CH 3C(CH 2)4CCH(11).ACH 33CH 3CHCH CH 2CH 3CH 3BO CH 3O 2.解释下列现象:(1)为什么乙二醇及其甲醚的沸点随分子量的增加而降低?b.p.CH 2OH CH 2OH197CCH 2OCH 3CH 2OH125CCH 2OCH 3CH 2OCH 384C(2)下列醇的氧化(A)比(B)快?(A)OHMnO 2O(B)MnO 2OHO(3)在化合物(A )和(B )的椅式构象中,化合物(A )中的-OH 在e 键上,而化合物(B )中的-OH 却处在a 键上,为什么?(A)OH(B)OOOH解答:2.(1)醇分子中的羟基是高度极化的,能在分子间形成氢键,这样的羟基越多,形成的氢键越多,分子间的作用力越强,沸点越高。
甲醚的形成导致形成氢键的能力减弱,从而沸点降低。
(2)从产物看,反应(A )得到的是共轭体系的脂芳酮,而(B )没有这样的共轭体系。
Synthesis, Crystal Structure, and Photoluminescence of Sr-α-SiAlON Eu2+
Synthesis,Crystal Structure,and Photoluminescenceof Sr-a -SiAlON:Eu 21Kousuke Shioi wSHOWA DENKO K.K.,Midori,Chiba 267-0056,JapanNaoto Hirosaki,*Rong-Jun Xie,*Takashi Takeda,and Yuan Qiang LiNational Institute for Materials Science,Tsukuba,Ibaraki 305-0044,JapanYoshitaka MatsushitaNational Institute for Materials Science,NIMS-SPring-8,Sayo,Hyogo 679-5148,JapanSr-containing a -SiAlON (Sr m /2Si 12-m –n Al m 1n O n N 16–n :Eu 21)phosphor was obtained as a major phase in compositions hav-ing small m and n values,by firing the powder mixture of SrSi 2,SrO,a -Si 3N 4,AlN,and Eu 2O 3at 20001C for 2h under 1MPa nitrogen atmosphere.The crystal structure of Sr-a -SiAlON was refined by the Rietveld analysis of the synchrotron X-ray powder diffraction pattern.The crystal structure showed that the Sr–N2bonding distance of Sr-a -SiAlON was fairly large compared with that of Ca-a -SiAlON.The displacement of N2sites prob-ably allow the interstices in a -SiAlON to accommodate the in-troduction of the large Sr ion.Sr-a -SiAlON:Eu 21phosphor has an excitation wavelength ranging from the ultraviolet region to 500nm and emits a strong yellow light.I.IntroductionWHITE light-emitting diodes (white LEDs)are considered as next-generation solid-state lighting systems because of their promising features such as low power consumption,high efficiency,long lifetime,and the lack of mercury.The availabil-ity of white-LEDs should open up a great number of new ex-citing application fields:white light sources to replace traditional incandescent and fluorescent lamps,backlights for portable elec-tronics,automobile headlights,medical,and architecture light-ing,etc.1–5Recently,rare earth-doped (oxy)nitride phosphors are gaining considerable attention due to their nontoxicity,and promising luminescence properties that enable them to be used in white-LEDs.Typical examples are red M 2Si 5N 8:Eu 21(M 5Ca,Sr,and Ba)6,7and CaAlSiN 3:Eu 21,8,9yellow Ca-a -SiAlON:Eu 21,10–13green b -SiAlON:Eu 21,14and yellow Ce-melilite.15Among these (oxy)nitride luminescence materials,Eu 21-doped a -SiAlON has a strong absorption in the range of 280–470nm and exhibits a broad yellow emission band covering the range of 550–590nm,11which is,therefore,expected to be used in white LEDs when combined with a blue LED chip.16In addition,due to its unique crystal structure,the a -SiAlON host lattice has the following advantages:(i)better flexibility of ma-terial design without changing the crystal structure,(ii)strong absorption in the visible light spectral region and long wave-length emissions,and (iii)chemical and thermal stability,as its basic structure is based on (Si,Al)–(O,N)4tetrahedral networks.a -SiAlON ceramics have been widely studied as structural materials because of their low linear expansion coefficients,high strength and hardness,and high thermal and chemical stabili-ties.It has an overall composition given by the formulaM m =v Si 12-m -n Al m þn O n N 16-n(1)where M is the modifying cations such as Li,Mg,Ca,Y,and rare earth (excluding La,Ce,Pr,and Eu),and v is the valency of the cation M.The crystal structure of a -SiAlON is derived from a -Si 3N 4by partial replacement of Si 41by Al 31and stabilized by trapping cations M into the interstices of the (Si,Al)–(O,N)4network.17It has been generally accepted that Sr 21ion alone cannot stabilize the a -SiAlON structure due to its large ionic size,but it can if codoped with calcium or yttrium.18Hwang addressed that the reaction product from the powder mixture with the com-position of Sr alone a -SiAlON without Y and Ca was the mixture of (a 1b )-SiAlON.Similar observations were also made by Man-dal 19and Liu et al .20A common feature of these reports is that the composition of Sr single-doped a -SiAlON has large m and n values.In this work,the synthesis of Sr-a -SiAlON:Eu 21with small m and n compositions is attempted,and the crystal structure of Sr-a -SiAlON is analyzed by the Rietveld refinement and then compared with that of Ca-a -SiAlON.Finally,the luminescent properties of Sr-a -SiAlON:Eu 21phosphor are reported.II.Experimental ProcedureSr-a -SiAlON:Eu 21samples were prepared from a -Si 3N 4(SN-E10,Ube Industries Ltd.,Tokyo,Japan),SrSi 2(KojyundoChemicalSr 1.5Al 3N 4Si 3N 4Fig.1.Schematic illustration of the a -SiAlON plane with the compo-sition numbers in Table I.D.Johnson—contributing editor*Member,The American Ceramic Society.wAuthor to whom correspondence should be addressed.e-mail:shioi.kousuke@nims.go.jpManuscript No.26102.Received April 7,2009;approved August 13,2009.J ournalJ.Am.Ceram.Soc.,93[2]465–469(2010)DOI:10.1111/j.1551-2916.2009.03372.x r 2009The American Ceramic Society465Laboratory Co.Ltd.,Saitama,Japan),SrO (Kojyundo Chemical Laboratory Co.Ltd.),AlN (Type F,Tokuyama Co.Ltd.,Shunan-shi,Japan),and Eu 2O 3(Shin-Etsu Chemical Co.Ltd.,Tokyo,Japan).SrSi 2was used as the Sr 21source to investigate small n compositions with an aim to eliminate the influence of the oxidation of raw materials in air,because SrSi 2is very stable against oxidation compared with metallic Sr or Sr 3N 2.The chemical compositions of the samples are plotted and listed in Fig.1and Table I.The powder mixtures were ground in the Si 3N 4mortar and pestle.The mixed powders were loaded in h-BN crucibles and then fired in a graphite resistance furnace at 20001C for 2h under 1MPa nitrogen atmosphere.The Eu 31ion in the starting powder Eu 2O 3is reduced to Eu 21under the nitrogen atmosphere during firing,which is confirmed by the absorption and emission spectra given later.Ca-a -SiAlON and Sr-a -SiAlON samples for the Rietveld refinement with nominal compositions Ca 0.375Si 11.25Al 0.75N 16and Sr 0.375Si 11.25Al 0.75N 16were also prepared by using the same firing conditions.The phase products of synthesized powders were identified by X-ray powder diffraction (XRD),operating at 40kV and 40mA and using Cu K a radiation (RINT2000,Rigaku,Tokyo,Japan).A step size of 0.0212y was used with a scan speed of 21/min.High-resolution synchrotron powder XRD data for Rietveldrefinements were recorded using wavelength l 50.65297Aat the NIMS beamline BL15XU of SPring-8synchrotron radiation facility.21The crystal structures were refined by the Rietveld method using the computer program RIETAN-FP,22and then visualized using the software package VESTA.23The photoluminescence spectra of the powder samples were mea-sured by a fluorescent spectrophotometer (Model F-4500,Hitachi Ltd.,Tokyo,Japan)at room temperature with a 150W Ushio xenon short-arc lamp.The emission spectrum was corrected for the spectral response of a monochromater and photomultiplier tube by a light diffuser (model R928P,Hamamatsu,Bridgewater,NJ)and tungsten lamp (10V,4A;Noma Electric Corp.,New York,NY).The excitation spectrum was also corrected for the spectral distribution of the xenon lamp intensity by measuring rhodamine-B as reference.III.Results and Discussion(1)SynthesisFigure 2shows the XRD patterns of samples with different m values (m 50.40–2.00)and a constant n value (n 50.02).As seen in Fig.2,the a -SiAlON phase is obtained as a major phase and SrSi 6N 8as a minor phase in samples with the m value varying from 0.70to 0.80,indicating that Sr 21can be dissolved in the a -SiAlON structure.The b -phase (b -Si 3N 4or b -SiAlON)is ob-served to coexist with a -SiAlON when m is below 0.70,the vol-ume of which increases with decreasing m value.With m values 40.80,the volume of SrSi 6N 8increases obviously,suggesting that the solubility limit of Sr 21in a -SiAlON is o 0.80.Figure 3presents XRD patterns of the samples with different n values (n 50–0.30)and a constant m value (m 50.75)As shown,the volume of the b -phase increases when n increases.As n stands for the oxygen content in the composition,a large n indicates an oxygen-rich composition.As mentioned previously,24the incre-Table I.Starting Compositions and Chemical Formula of the SamplesNo.m n Starting composition (wt%)Chemical formulaSrSi 2SrO a -Si 3N 4AlN Eu 2O 310.400.02 4.53091.84 3.010.62Sr 0.18Eu 0.02Si 11.58Al 0.42O 0.02N 15.9820.500.02 5.77089.90 3.720.61Sr 0.23Eu 0.02Si 11.48Al 0.52O 0.02N 15.9830.600.027.00087.97 4.420.61Sr 0.28Eu 0.02Si 11.38Al 0.62O 0.02N 15.9840.700.028.22086.05 5.110.61Sr 0.33Eu 0.02Si 11.28Al 0.72O 0.02N 15.9850.750.028.83085.10 5.460.61Sr 0.355Eu 0.02Si 11.23Al 0.77O 0.02N 15.9860.800.029.44084.15 5.810.61Sr 0.38Eu 0.02Si 11.18Al 0.82O 0.02N 15.987 1.100.0213.03078.527.850.60Sr 0.53Eu 0.02Si 10.88Al 1.12O 0.02N 15.988 1.500.0217.72071.1810.510.59Sr 0.73Eu 0.02Si 10.48Al 1.52O 0.02N 15.989 2.000.0223.40062.2713.750.58Sr 0.98Eu 0.02Si 9.98Al 2.02O 0.02N 15.98100.750.058.060.5485.13 5.660.61Sr 0.355Eu 0.02Si 11.20Al 0.80O 0.05N 15.95110.750.10 6.80 1.4285.19 5.990.60Sr 0.355Eu 0.02Si 11.15Al 0.85O 0.10N 15.90120.750.20 4.29 3.1885.29 6.640.60Sr 0.355Eu 0.02Si 11.05Al 0.95O 0.20N 15.80130.750.30 1.82 4.9185.407.280.60Sr 0.355Eu 0.02Si 10.95Al 1.05O 0.30N 15.70SSN,SrSi 6N 8;a ,Sr-a -SiAlON;AN-p,SrSi 10Àn Al 181n O n N 32Àn ;X,Unknown phase;s,strong;m,medium;w,weak.20I n t (a .u . ):β:αm=1.50m=1.10m=0.80m=0.75m=0.60m=0.70m=0.40m=0.50m=2.002530354045502θ (deg): SrSi 6N 8Fig.2.X-ray powder diffraction patterns of the compositions with different m values (n 50.02),a ,a -SiAlON;b ,b -SiAlON.20I n t (a .u .):α:βn=0.10n=0.20n=0.05n=0.02n=0.302530354045502θ ( deg )Fig.3.X-ray powder diffraction patterns of the compositions with different n values (m 50.75),a ,a -SiAlON;b ,b -SiAlON.466Journal of the American Ceramic Society—Shioi et al.Vol.93,No.2ment of b -phase with increasing n values is attributable to the excess formation of liquid phase during firing,and in turn pro-motes the formation of b -phase.Therefore,we demonstrate that Sr-a -SiAlON can be formed as the major phase in compositions with small m and n values (m 50.70–0.80and n 50–0.05).As mentioned above,Sr solely doped a -SiAlON was not avail-able in previous studies.It is due to the fact that the m and n values are too large in those investigations (Hwang et al .,18m 51and n 51;Mandal,19m 51.25and n 51.15;Liu et al .,20m 51.6,n 51.6),which make Sr unable to stabilize the a -SiAlON.(2)Crystal StructureThe diffraction data obtained by synchrotron powder X-ray of Sr-a -SiAlON and Ca-a -SiAlON with the nominal compositionsSr 0.375Si 11.25Al 0.75N 16and Ca 0.375Si 11.25Al 0.75N 16were used for structural refinement.Because the Sr-a -SiAlON sample contains a small amount of SrSi 6N 8,a two-phase structural refinement was conducted on Sr-a -SiAlON.As shown in Fig.4(a),a fairly good result was obtained,and the final refinement converged with the reliability indexes:R wp 51.31%,R p 50.89%.R I and R F are 4.85%,2.66%for Sr-a -SiAlON and 4.18%,1.54%for SrSi 6N 8,respectively.The mole fraction of Sr-a -SiAlON to SrSi 6N 8is 0.96–0.04.Figure 4(b)shows the refinement result of Ca-a -SiAlON.The reliability indexes obtained are:R wp 52.39%,R p 51.43%,R I 52.39%,and R F 51.29%.The refined fractional coordinates of Sr-a -SiAlON and Ca-a -Si AlON are listed in Table II.The occupancy of each Ca and Sr were 0.1825(7)and 0.1380(7),respectively.The smaller occupancy of Sr1is due to the formation of SrSi 6N 8.The calculated occupancy of Ca-a -SiAlON is smaller than that derived from the nominal composition:0.1875.The deviation of the occupancy of Ca-a -SiAlON can be ascribed to the vol-atilization of Ca at the high firing temperature of 20001C.It is seen that Ca-a -SiAlON and Sr-a -SiAlON have similar latticeconstants,and they are a 57.79277(3)A ,c 55.65325A for Ca-a -SiAlON and a 57.79189(5)A ,and c 55.65377A forSr-a -SiAlON.As mentioned previously,the lattice constants decrease with decreasing m value,13indicating that the lattice constants of Sr-a -SiAlON are influenced by the formation of SrSi 6N 8.The crystal structure of Sr-or Ca-a -SiAlON is shown in Fig.5(a).The a -SiAlON structure has the expanded a -Si 3N 4structure built up of the (Si,Al)–(O,N)network.17The intro-duction of Ca or Sr in the sevenfold coordination sites stabi-lizes the a -SiAlON structure.The local structure of the Ca or Sr site in the a -SiAlON structure is shown in Fig.5(b).Selected bonding distances and bonding angles are listed in Table III.The first nearest Ca/Sr–N2bond is much shorter than the other six Ca/Sr–N bonds.Ca–N2and Sr–N2bondingdistances are 2.367(5)Aand 2.412(7)A ,respectively,and the difference of the bonding distances between Ca–N2and Sr–N2is large compared with the other six bonds.Si/Al1–N2–Si/Al1bond angles of Ca-a -SiAlON and Sr-a -SiAlON are 116.7(2)1and 117.5(3)1,respectively.This means that the displacement of N2sites parallel to the c axis probably allow the interstices in a -SiAlON to accommodate the introduction of the large Sr ion.(3)Photoluminescence PropertiesFigure 6shows the typical excitation and emission spectra:of (a)Sr-a -SiAlON:Eu 21,(b)Ca-a -SiAlON:Eu 21phosphors.The excitation and emission spectra of Sr-a -SiAlON:Eu 21are comparable with those of Ca-a -SiAlON:Eu 21.The exci-52015302540351060555045I n t e n s i t y (b)52015302540351060555045I n t e n s i t y(a)2θ / deg2θ / degFig.4.Observed and calculated X-ray powder diffraction patterns for nominal compositions:(a)Sr 0.375Si 11.25Al 0.75N 16,(b)Ca 0.375Si 11.25Al 0.75N 16.Solid line is the pattern calculated from the refined crystal structure.Residual errors are drawn at the bottom of the figure.Vertical short lines are the permitted peak positions satisfying the Bragg condi-tion.The first row is Sr-a -SiAlON,and the second row is SrSi 6N 8in (a).Table II.The Refined Atomic Coordinates,Occupancies,and Isotropic Atomic Displacement Parameters for Ca-and Sr-a -SiAlONAtomWykoff positionOccxyzB (A2)Ca-a -SiAlONCa 2b 0.1825(7)1/32/30.23604(4)0.460(67)Si/Al16c 0.8175/0.18250.51156(6)0.0824(6)0.21097(48)0.424(8)Si/Al26c 0.8175/0.18250.16813(5)0.2527(5)0.00271(48)0.256(7)N12a 10000.34N22b 11/32/30.65475(55)0.34N36c 10.34473(12)À0.04598(15)À0.00922(63)0.34N46c 10.31852(13)0.31533(14)0.25714(56)0.34Sr-a -SiAlON Sr 2b 0.1380(7)1/32/30.2357(9)0.77(8)Si/Al16c 0.862/0.1380.51122(10)0.08219(9)0.2110(8)0.40(1)Si/Al26c 0.862/0.1380.16817(8)0.25288(7)0.0015(8)0.21(1)N12a 10000.34N22b 11/32/30.6624(9)0.34N36c 10.3453(2)À0.0426(2)À0.0037(11)0.34N46c10.3209(2)0.3139(2)0.2582(9)0.34Space group:P 31c (no.159).Refined lattice parameters are Ca-a -SiAlON:a 57.79277(3)A,c 55.65325(1)A ,Sr-a -SiAlON:a 57.79189(5)A ,c 55.65377(2)A .February 2010Synthesis,Crystal Structure,and Photoluminescence of Sr-a -SiAlON:Eu 21467tation spectrum of Sr-a -SiAlON:Eu 21covers the spectral re-gion from the UV to the visible part.Two broad bands are observed in the excitation spectrum with the maxima at about 288and 399nm corresponding to 4f 7-4f 65d transition of Eu 21.It is consistent with previous study on Ca-a -Si AlON:Eu 21.13The emission spectrum shows a single intense broad emission band ranging from 470to 750nm,peaking at about 575nm,which is attributable to the permitted 4f 65d -4f 7transition of Eu 21.The emission intensities of Sr-a -Si AlON:Eu 21(583nm)and Ca-a -SiAlON:Eu 21(575nm)were about 122%and 116%of YAG:Ce 31(P46-Y3).The emission peak of Sr-and Ca-a -SiAlON:Eu 21were longer than that of YAG:Ce 31(560nm).It means that the Sr-and Ca-a -Si AlON:Eu 21phosphors could be good yellow phosphor can-didates for creating warm white light when combined with blue LED.A very weak emission band centered at 450nm is ascribed to the luminescence of the small amount of SrSi 6N 8:Eu 21.25The characteristic Eu 31luminescence,which ex-hibits sharp and line-shaped spectrum between 600and 630nm is not observed.This suggests that the europium ion in Sr-a -SiAlON phosphor is in the divalent state.In comparisonwith Ca-a -SiAlON:Eu 21,the positions of the excitation and emission spectra are very similar (Fig.6),because the PL spectra are fixed by the network of (Si,Al)–(O,N)in a -Si AlON and nearly independent of the local structure around Sr (Eu 21)or Ca (Eu 21)ions.IV.ConclusionsNovel Sr-a -SiAlON:Eu 21phosphors have been successfully syn-thesized by gas-pressure sintering at 20001C for 2h under 1MPa nitrogen atmosphere.Nearly single phase of Sr-a -SiAlON:Eu 21sample was obtained with small m and n values (m 50.70–0.80and n 50–0.05).The Rietveld refinements have revealed that the displacement of N2site parallel to the c -axis could be the main reason for the introduction of Sr atom into the a -SiAlON struc-ture.This phosphor shows the wide excitation spectrum cover-ing from the ultra violet region to 500nm and emits a strong yellow light.It is expected that Sr-a -SiAlON:Eu 21phosphor can also be a good wavelength-conversion yellow phosphor for use in white LEDs based on a blue (Ga,In)N chip.AcknowledgmentsWe thank Drs.M.Tanaka,H.Yoshikawa,and K.Kobayashi of the National Institute for Materials Science for their suggestions and encouragements.We thank Dr.Y.Katsuya and Ms.J.Uchida of SPring-8service for their support in the diffraction experiments.References1S.Nakamura and G.Fasol,The Blue Laser Diode:GaN Based Light Emitters and Lasers .Springer-Verlag,Berlin,1997.2Y.Sato,N.Takahashi,and S.Sato,‘‘Full-Color Fluorescent Display Devices Using a Near-UV Light-Emitting Diode,’’Jpn.J.Appl.Phys.,35[7A]838–9(1996).3Y.Narukawa,I.Niki,K.Izuno,M.Yamada,Y.Murazaki,and T.Mukai,‘‘Phosphor-Conversion White Light Emitting Diode Using InGaN Near-Ultra-violet Chip,’’Jpn.J.Appl.Phys.,41[4A]371–3(2002).4Y.D.Huh,J.H.Shim,Y.Kim,and Y.R.Do,‘‘Optical Properties of Three-Band White Light Emitting Diodes,’’J.Electrochem.Soc.,150[2]H57–60(2003).5C.W.Tang,S.A.Van Slyke,and C.H.Chen,‘‘Electroluminescence of Doped Organic Thin Films,’’J.Appl.Phys.,65[9]3610–6(1989).ca(b)(a)bSi/Al1iiiN4vN4viN2ivN3ivCa/Sr ivN3viN3vN4ivSi/Al1iiSi/Al1iFig.5.(a)Crystal structures of a -SiAlON projected along the [110]direction.(b)The local structure of the Ca/Sr site in the a -SiAlON structure.Table III.Selected Bonding Distances and Angles in the LocalStructure of the Ca/Sr SiteCa-a -SiAlONSr-a -SiAlONDistance (A )M iv –N2iv 2.367(5) 2.412(7)M iv –N3vi 2.597(3) 2.600(4)M v –N3v 2.597(3) 2.600(4)M iv –N3iv 2.597(3) 2.600(4)M iv –N4v 2.6847(7) 2.7049(12)M iv –N4vi 2.6847(7) 2.7049(11)M iv –N4iv 2.6847(11) 2.705(2)Average 2.602 2.618Angle (deg)Si/Al1ii –N2iv –Si/Al1iii 116.7(2)117.5(3)Si/Al1i –N2iv –Si/Al1ii 116.7(2)117.5(2)Si/Al1iii –N2iv –Si/Al1i116.74(13)117.5(2)Symmetry operations are (i)x ,y ,z ;(ii)Ày ,x Ày ,z ;(iii)Àx 1y ,Àx ,z ;(iv)y ,x ,z 11/2;(v)x Ày ,Ày ,z 11/2;(vi)Àx ,Àx 1y ,z 11/2.M 5Ca and Sr.P L e m / e x -I n t ( a .u )(a)ExcitationEmission 200Wavelength ( nm )P L e m / e x -I n t ( a .u )(b)ExcitationEmission λem = 575 nm λem = 583 nm λex = 400 nmλex = 400 nmCa-α-SiAlON300400500600700200Wavelength ( nm )300400500600700Sr-α-SiAlONFig.6.Excitation and emission spectra of the samples with the nominal compositions:(a)Sr 0.355Eu 0.02Si 11.23Al 0.77O 0.02N 15.98,(b)Ca 0.355Eu 0.02Si 11.23Al 0.77O 0.02N 15.98.468Journal of the American Ceramic Society—Shioi et al.Vol.93,No.26H.A.Hoppe,H.Lutz,P.Morys,W.Schnick,and A.Seilmeier,‘‘Luminescence in Eu21-doped Ba2Si5N8:Fluorescence,Thermoluminescence,and Upconver-sion,’’J.Phys.Chem.Solids,61[12]2001–6(2000).7Y.Q.Li,J.E.J.van Steen,J.W.H.van Krevel,G.Botty,A.C.A.Delsing, F.J.DiSalvo,G.de With,and H.T.Hintzen,‘‘Luminescence Properties of Red-Emitting M2Si5N8:Eu21(M5Ca,Sr,Ba)LED Conversion Phosphors,’’pd.,417,273–9(2006).8K.Uheda,N.Hirosaki,Y.Yamamoto,A.Naito,T.Nakajima,and H.Yama-moto,‘‘Luminescence Properties of a Red Phosphor,CaAlSiN3:Eu21,for White Light-Emitting Diodes,’’Electrochem.Solid State Lett.,9,H22–5(2006).9K.Uheda,N.Hirosaki,and H.Yamamoto,‘‘Host Lattice Materials in the System Ca3N2-AlN-Si3N4for White Light Emitting Diode,’’Phys.Status Solid, A203,2712–7(2006).10J.W.H.van Krevel,J.W.T.van Rutten,H.Mandal,H.T.Hintzen,and R.Metselaar,‘‘Luminescence Properties of Terbium-,Cerium-,or Europium-Doped a-Sialon Materials,’’J.Solid State 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Sakuma,‘‘Optical Properties of Eu21in a-SiAlON,’’J.Phys.Chem.B,108[32] 12027–31(2004).14N.Hirosaki,R.-J.Xie,K.Kimoto,T.Sekiguchi,Y.Yamamoto,T.Suehiro, and M.Mitomo,‘‘Characterization and Properties of Green-Emitting b-SiAlON: Eu21Powder Phosphors for White Light-Emitting Diodes,’’Appl.Phys.Lett.,86, 211905,3pp(2005).15J.W.H.van Krevel,H.T.Hintzen,R.Metselaar,and A.Meijerink,‘‘Long Wavelength Ce31Emission in Y–Si–O–N Materials,’’pd.,268,272–7(1998).16K.Sakuma,N.Hirosaki,and R.-J.Xie,‘‘Red-Shift of Emission Wavelength Caused by Reabsorption Mechanism of Europium Activated Ca-a-SiAlON Ce-ramic Phosphor,’’J.Lumin.,126,843–52(2007).17G.Z.Cao and R.Metselaar,‘‘a0-Sialon Ceramics:A Review,’’Chem.Mater., 3[2]242–52(1991).18C.J.Hwang,D.W.Susnitzky,and D.R.Beaman,‘‘Preparation of Multi-cation a-SiAlON Containing Strontium,’’J.Am.Ceram.Soc.,78[3]588–92 (1995).19H.Mandal,‘‘New Developments in a-SiAlON Ceramics,’’J.Eur.Ceram. Soc.,19,2349–57(1999).20G.Liu,K.Chen,H.Zhou,K.Ren,C.Pereira,and J.F.M.Ferreira,‘‘Fab-rication of(Ca1Yb)-and(Ca1Sr)-Stabilized a-SiAlON by Combustion Synthe-sis,’’Mater.Res.Bull.,41,547–52(2006).21M.Tanaka,Y.Katsuya,and A.Yamamoto,‘‘A New Large Radius Imaging Plate Camera High-Resolution and High-Throughput Synchrotron X-ray Powder Diffraction by Multiexposure Method,’’Rev.Sci.Instrum.,79,075106, 6pp(2008).22F.Izumi and K.Momma,‘‘Three-Dimensional Visualization in Powder Diffraction,’’Solid State Phenom.,130,15–20(2007).23Momma and K.Izumi,‘‘VESTA:A Three-Dimensional Visualization System for Electronic and Structural Analysis,’’J.Appl.Crystallogr.,41,653–8(2008). 24H.L.Li,R.-J.Xie,N.Hirosaki,T.Suehiro,and Y.Yajima,‘‘Phase Purity and Luminescence Properties of Fine Ca-a-SiAlON:Eu Phosphors Synthesized by Gas Reduction Nitridation Method,’’J.Electrochem.Soc.,155[6]J175–9(2008).25K.Shioi,N.Hirosaki,R.-J.Xie,T.Takeda,and Y.Q.Li,‘‘Luminescence Properties of SrSi6N8:Eu2,’’J.Mater.Sci.,43[16]5659–61(2008).&February2010Synthesis,Crystal Structure,and Photoluminescence of Sr-a-SiAlON:Eu21469。
semi-syntheticar...
Semi-synthetic aristolactams—inhibitors of CDK2enzymeVinod R.Hegde *,Scott Borges,Haiyan Pu,Mahesh Patel,Vincent P.Gullo,Bonnie Wu,Paul Kirschmeier,Michael J.Williams,Vincent Madison,Thierry Fischmann,Tze-Ming ChanSchering Plough Research Institute,2015Galloping Hill Road,Kenilworth,NJ 07033,USAa r t i c l e i n f o Article history:Received 7August 2009Revised 23December 2009Accepted 4January 2010Available online 7January 2010Keywords:Semi-synthetic analogs Aristolactams IC 50SARa b s t r a c tSeveral analogs of aristolochic acids were isolated and derivatized into their lactam derivatives to study their inhibition in CDK2assay.The study helped to derive some conclusions about the structure–activity relation around the phenanthrin moiety.Semi-synthetic aristolactam 21showed good activity with inhi-bition IC 50of 35nM in CDK2assay.The activity of this compound was comparable to some of the most potent synthetic compounds reported in the literature.Ó2010Elsevier Ltd.All rights reserved.In the preceding Letter we have reported on the isolation of a potent CDK2enzyme inhibitor SCH 546909,a natural product aris-tolactam analog with an inhibition IC 50of 140nM.This prompted us to undertake a semi-synthetic study of different analogs from this class.Many total syntheses of aristolactam analogs have been reported in the literature,1,2however sub-structure literature searches revealed that these compounds could be easily prepared from naturally occurring,aristolochic acids.HO H 3CONHOHOSCH 546909Several publications and reviews have been published on the occurrence,synthesis and biological activities of aristolochic acids.Aristolochic acids and aristolactams are classified as aporphinoids because of their basic skeleton which bears a distinct similarity to that of aporphins.Aristolochic acids exhibit tumor inhibitory activ-ity against the adenocarcinoma 755test system but in mice they induced papiloma.3They are also known to form covalent DNA adducts by enzymatic reductive activation of aristolochic acids in the presence of DNA.4They are also shown to induce mutagenicity in mice.5Aristolochic acid is commercially available from SigmaChemical Co.and ACROS.The commercially available aristolochic acid is a complex mixture of several analogs,with the major com-ponents being aristolochic acids II &I in 1:4ratio.We have sepa-rated commercial aristolochic acid mixtures on a preparative HPLC using YMC ODS-A C-18,10l m,5Â50cm HPLC column,eluting with 0.05%trifluoroacetic acid and acetonitrile (60:40)to obtain compounds 1–8.A typical 600mg of commercial aristolo-chic acid afforded 27.7,4.6,7.8,71.6,5.4,6.8,315.8,and 3.2mg of aristolochic acid C (5),6aristolochic D (7),77-hydroxy aristolo-chic A(6),8aristolochic acid II (1),aristolochic acid IV (4),97-meth-oxy aristolochic acid A (3),10aristolochic acid I (2),2and aristolochic acid III (8).11In our semi-synthetic modifications to prepare aristolactam analogs,the aristolochic acids were first converted to their lactams.The purified aristolochic acids were hydrogenated in ethanolic solution under 40psi hydrogen in presence of Pd/C catalyst,over-night at room temperature.The amino compound produced on reduction of nitro group,on further ring closure results in lactam.After separation and derivatization to the resulting lactam,the aromatic phenol ether derivatives were deprotected with BBr 3in methylene chloride solution.A typical demethylation 12involved stirring the aristolochic methyl ethers (15mg)in CH 2Cl 2(50ml)at 0°C with the dropwise addition of BBr 3(7.5ml,1M)in CH 2Cl 2at 0°C and then continue stirring overnight at room temperature.The reaction mixture was quenched in ice,extracted with ethyl acetate,and dried.The demethylated product was purified by HPLC.The Methylenedioxy group was removed by stirring aristolac-tams in CH 2Cl 2at 0°C and dropwise addition of a solution of PCl 5(1:1ratio).The reaction mixture was slowly allowed to attain room0960-894X/$-see front matter Ó2010Elsevier Ltd.All rights reserved.doi:10.1016/j.bmcl.2010.01.007*Corresponding author.Tel.:+19088203871;fax:+19088206166.E-mail address:**********************(V.R.Hegde).Bioorganic &Medicinal Chemistry Letters 20(2010)1384–1387Contents lists available at ScienceDirectBioorganic &Medicinal Chemistry Lettersj o ur na l h om e pa ge :w w w.e lse v ie r.c om /lo c at e/bm c ltemperature during2h and then quenched with ice,extracted with CH2Cl2and dried.The O-dihydroxy compound formed was purified by HPLC.3,4-Dihydroxy-12-chloro aristolactams were prepared from methylenedioxy containing derivatives via treatment with the dropwise addition of PCl5(1:2.5ratio)in CH2Cl2at0°C and slowly allowing the reaction mixture to attain room temperature during 3h.The reaction mixture was quenched in ice,extracted with CH2Cl2and dried.The halogenated product was further purified by HPLC.O OCOOHNO2OONR1R2R31. R1 = R2 = R3 = -H2. R1 = -OCH3, R2 = R3 = -H3. R1 = R2 = -OCH3, R3 = -H4. R1 = R3 = -OCH3, R2 = -H5.R1 = R2 = -H, R3 = -OH6. R1 = -OCH3, R2 = -OH, R3 = -H7. R1 = -OCH3, R2 = -H, R3 = -OH8. R1 = -OH,R2 = R3 = -H9. R1 = R2 = -OCH3, R3 = -HOR1R2R3R4R515. R1 = R2 = R3 = R4 = R5 =-H16. R1 = -OCH3, R2 = R3 = R4 =R5 = -H17. R1 = R2 =-OCH3 ,R3 =R4 = R5 = -H18. R1 = R3 = -OCH3, R2 = R4 = R5 = -H19. R1 = -OCH3, R2 = -OH, R3 = R4 =R5 = -H20. R1 = -OCH3, R3 = -OH, R2 = R4 = R5 = -H21. R1 = -OH, R2 = R3 = R4 = R5 = -H22. R1 = R2 = -OH, R3 = R4 = R5 = -H23. R1 = R3 = -OH, R2 = R4 = R5 = -H24. R1 = R2 = R4 = R5 = -H, R3 = -OH,25. R1 = -OCH3, R2 = R3 = R4 = -H, R5 = -CH326. R1 = -OH, R2 = R3 = R4 = -H, R5 = -CH3ARISTOLOCHIC ACID ANALOGSHO HOCOOHNO2R4R1R2R310. R1 = R2 = R3 = R4 = -H11. R1 = R2 = R3 = -H, R4 = -Cl12. R1 = -OCH3, R2 = R3 = R4 = -H13. R1 = -OH, R2 = R3 = R4 = -H14. R1 = -OCH3, R2 = R3 = -H, R4 = -Cl 27. R1 = R2 = R3 = R4 = -H28. R1 = R2 = R3 = -H, R4 = -Cl29. R1 = -OCH3, R2 = R3 = R4 = -H30. R1 = -OH, R2 = R3 = R4 = -H31. R1 = -OCH3,R2 =R3 = -H, R4 = -ClHOHONHOR4R1R2R3The aristolochic acid analogs prepared were tested in CDK2as-say13with the resulting inhibition IC50s are tabulated in Table1. Many analogs showed CDK2activity>10l M,however compounds 13,16,19,21,and24exhibited CDK2inhibition under10l M. Compound21showed a CDK2inhibition IC50of35nM,potency similar to the most potent CDK2inhibitor reported in the litera-ture14Compound13,having a hydroxyl group at C-9also showed activity in the l M range.Several natural products,like aporphinoids,morphine,and fused berberine classes of compounds,were also tested to evaluate importance of the lactam ring in the CDK2activity.All these com-pounds excepting sinomenine,sinoacutine,and tetrahydroberber-ine,have tetrahydro pyridine ring attached to phenanthrine moiety.Sinomenine and sinoacutine have morphine like ring sys-tem but tetrahydroberberine has two tetrahydro-isoquinoline ring system.All these compounds failed to show inhibition in CDK2as-say at50l M.Only compound21,displayed strong CDK2inhibition,about threefold better than the natural product SCH546909.Based on the activity profile of the different aristolochic acid and aristolactam analogs,it appears the lactam ring is essential for potent CDK2inhibition.This has been shown to be true for sev-eral potent inhibitors reported in literature.31,32Hydroxyl groups at C-7or C-9positions also appear to enhance CDK2inhibition. Additionally,theprotection of the dihydroxy groups atthe C-4 and C-5positions contributes toward the potency.However,pro-tection of amide–NH by a methyl group or substitution by a halo-gen at C-10results in reduced activity.The observations are only empirical and a detailed study would be necessary to evaluate a complete structure–activity relationship.Protection increasesthe potency in CDK2assay-CH3 in this positiondecreases activityhalogen in this positiondecrease in potencyincreases the potencyAristolochic acids and aristolactams have phenanthrin aromatic moiety similar to another class of natural product that includes staurosporine,isolated from fungus.Staurosporins are also potent kinase inhibitors and have been extensively studied as antitumor compounds.Like staurosporine,these compounds are also planar molecules and are sparingly soluble in various solvents including water.Increasing the solubility properties by salt formation or by Table1CDK2inhibition IC50s of aristolochic acids and aristolactam analogs Compound CDK2IC50(l M)1>202>203>204>205306257258159>201013.4111812>3013 5.71416.51516151616 1.217>151815>1519 2.92018>3521180.03522>302318>502420,21 2.152519,21>352617>35274>3528>2529>353016>353110Dicentrine22>50Crebanine23>50Roemerine-HBr24>50Isocorydine25>50Corydine26>50Corytuberine27>50Sinoacutine28>50Sinomenine29>50Stephanine,25>50Tetrahydro-berberine30>50V.R.Hegde et al./Bioorg.Med.Chem.Lett.20(2010)1384–13871385forming inclusion compounds with b -cyclodextrin appear to improve cellular activity.Aristolactam 21was further tested in a kinase counter screen assays,along with the natural product SCH 546909and 3233,as shown in Table 2.The results indicate that the inhibitors share a similar activity in the CDC2(cyclin-A dependent kinase,$90%homology)assay,and a lesser selectivity in other kinases assays like CDK4,AUR2(Aurora kinase),MAPK (mitogen-activated protein kinase),and AKT (ATP kinase).Cellular activities:Compound 21,the most potent and selective CDK2inhibitor from this series,was evaluated in two cellular pro-liferation assays:a colony forming assay and a soft agar growth as-say.In the soft agar growth assay compound 21showed comparable activity to 32,although compound 32appeared to lose some potency in this assay format compared to the clonogenicity assay (Table 2).In the clonogenicity assay using MCF-7cells,all three compounds inhibited growth at similar micromolar pound 21inhibited proliferation of tumor cells,with IC 50values consistent with CDK2inhibitors that are competitive with respect to ATP.The anti-proliferative activity of the com-pounds was up to eightfold selective for the tumor cells relative to the HFF normal cell line.The anti-proliferative activity of 21ar-rests the tumor cells and protects the normal cells from chemo-therapy-induced toxicity.32These data are consistent with an anti-proliferative mechanism expected for inhibition of CDK2and revealed that the aristolactam class of compounds have potential for treating proliferative disorders,including chemotherapy-in-duced alopecia.NN HNORPyrazoloquinolines32. R = -OCH 3 (SCH47089)Computer based interaction design of 21with CDK2enzyme:Thedocking experiments on CDK2enzyme with 21(SCH535270)and staurosporine were performed and are shown in Figure 1A and B.The computer docking model suggests the lactam of 21(SCH 535270)interacts with CDK2enzyme active sites in a manner anal-ogous to that observed for compounds of staurosporine class of inhibitors bound to fibroblast growth factor receptor kinase.34Two hydrogen bonds were formed between the c -lactam moi-ety of 21and CDK2.Specifically,the amide nitrogen was hydrogen bonded to the backbone carbonyl of glu-81of the CDK2enzyme and the lactam carbonyl oxygen was hydrogen bonded with the backbone NH of leu-83amide.Staurosporin also binds to the CDK2enzyme in a similar fashion.The C-9hydroxy group also ap-pears to stabilize the binding at some other sight of enzyme core.35SCH 535270,like staurosporin,is a planar molecule and exhibits similar biological properties.X-ray crystallography:Our attempts to determine the X-ray structure of inhibitor SCH 535270bound to CDK2have failed.The crystals were prepared by soaking the compound in presence of CDK2enzyme and cyclin A.The parameters like compound concentration and duration of soak were screened.Examination of the electronic density maps did not reveal the binding mode of the compound.In some cases,X-ray crystallogra-phy has failed to determine the co-structures of a compound bound to the CDK2protein even in the case of potent inhibitors.A possible explanation is that inhibitor binding requires the com-plete CDK2-cyclin-A complex,which is protocol in our screening assay.CDK2is activated by complexing with cyclin-A that induces conformational changes in the protein that affect the ATP binding site to some degree.The most significant effect involves a rotation of the C-helix,which alters the active-site geometry in the region of the triad of catalytic active-site residues Lys-33,Glu-51,and Asp-145.The amino group of Lys-33can be potential interaction site for inhibitors.The amino nitrogen appears to hydrogen bond with the oxygen of methylenedioxy group.Efforts to grow crystalsTable 2Inhibition (IC 50)of SCH 546909,21and 32in different kinases CompoundActivity IC 50(nM)Selectivity (nM)Cellular activity (l M)CDC2CDK4AUR2MAPK AKT SAG MCF7Clonogenicity SCH5469091402141420214035,335———32(SCH47089)2020020005000>50,000—>10 3.021(SCH535270)352009000350012,00011,4002–2.53.5Figure puter modeling of binding of 21(SCH 535270)and staurosporin with CDK2enzyme.1386V.R.Hegde et al./Bioorg.Med.Chem.Lett.20(2010)1384–1387of the activated CDK2-cyclin-A protein complex are in progress and will be reported in future publications.The aristolactam class of compounds represents a novel class of CDK2inhibitors.Exploration into semi-synthetic analogs provided a potent CDK2inhibitor from this class.Binding interactions by docking experiments suggested carbonyl of glu-81and NH of leu-83amide of the CDK2enzyme are involved in hydrogen bond-ing with the lactam functionality of aristolactams.CDK2inhibition causes an arrest of the cell cycle and exhibits a selective killing effect on several tumor cell lines.36AcknowledgmentsAuthors gracefully acknowledge Dr.E.Lees and Dr.R.Doll for their helpful discussion on CDK2inhibitors.References and notes1.Mix,D.B.;Guinaudeau,H.;Shamma,M.J.Nat.Prod.1982,45,657.2.Shamma,M.;Monit,J.C.Isoquinoline Alkaloids Research1972–1977;PlenumPress:New York,1978.3.(a)Kupchan,S.M.;Wormser,.Chem.1965,30,3792;(b)Kupchan,S.M.;Merianos,.Chem.1968,33,3735.4.(a)Stiborova,M.;Frei,E.;Breuer,C.A.;Schmeiser,H.H.Cancer Res.1990,50,5464;(b)Cinca,S.;Voiculetz,N.;Schmeiser,H.;Wiessler,M.J.Med.Biochem.1997,1,3.5.Pistelli,L.;Nieri,E.;Bilia,A.R.;Marsili,A.;Scarpato,R.J.Nat.Prod.1993,56,1605.6.Hong,L.;Sakagami,Y.;Marumo,S.;Xinmin,C.Phytochemistry1994,37,237.7.Nakanishi,T.;Iwasaki,K.;Nasu,M.;Miura,I.;Yoneda,K.Phytochemistry1982,21,1759.8.Wu,T.-S.;Leu,Y.-L.;Chan,Y.-Y.Chem.Pham.Bull.1999,47,571.9.De 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E.;Farnsworth,N.R.;Cordell,G.A.;Kinghorn,A.D.;Pezzuto,J.M.J.Nat.Prod.1995,58,598.25.Roblot,F.;Hocquemiller,R.;Cave,A.;Moretti,C.J.Nat.Prod.1983,46,862.26.Manske,R.H.F.Can.J.Res.1932,7,258.27.Wang,C.-C.;Kuoh,C.-S.;Wu,T.-S.J.Nat.Prod.1996,59,409.28.Kunitomo,J.;Ju-Ichi,M.;Yoshikawa,Y.;Chikamatsu,H.J.Pharm.Soc.Jpn.1974,94,97.29.Terui,Y.;Tori,K.;Maeda,S.;Sawa,Y.K.Tetrahedron Lett.1975,33,2853.30.Chen,C.Y.;MacLean,D.B.Can.J.Chem.1968,46,2501.31.Dumas,J.Exp.Opin.Ther.Patents2000,11,405.32.Davis,S.T.;Benson,B.G.;Bramson,H.N.;Chapman,D.E.;Dickerson,S.H.Science2001,291,134.33.Afonso,A.;Kelly,J.M.;Chackalamannil,S.U.S.Patent5459146,1995,pp13.34.Mohammadi,M.;McMahon,G.;Sun,L.;Tang,C.;Hirth,P.Science1997,276,955.35.Bramson,H.N.;Corona,J.;Davis,S.T.;Dickerson,S.H.;Edelstein,M.;Frye,S.V.,;Gampe,R.T.,Jr.;Harris,P.A.;Hassell,A.;Holmes,W.D.;Hunter,R.N.;Lackey,K.E.;Lovejoy,B.;Luzzio,M.J.;Montana,V.;Rocque,W.J.;Rusnak,R.D.;Shewchuk,L.;Veal,J.M.;Walker,D.H.;Kuyper,L.F.J.Med.Chem.2001,44, 4339.36.Walker,D.H.;Luzzio,M.;Veal,J.;Dold,K.;Edelstein,M.Proc.Am.Assoc.CancerRes.1999,40,A4783Physico-chemical properties:Aristolochic acid C(5):UV k max:225,256,308,410nm;FABMS328(M+H)+,350 (M+Na)+,366(M+K)+,1H NMR(DMSO-d6)d:10.63(COO H),8.48(9-H),8.46(d, J=4Hz,5-H),8.10(d,J=17Hz,8-H),7.75(s,2H),7.29(dd,J=17,4Hz,7-H),6.48(s,12-H2).13C NMR(DMSO-d6)ppm:168.0(11-C),159.8(6-C),145.8(3-C),145.5(4-C),143.1(10-C),132.5(8-C),131.0(4b-C),126.4(9-C),123.7(1-C),121.5(8a-C),118.8(7-C),117.2(10a-C),116.2(4a-C),111.9(2-C),111.1(5-C), 102.8(12-C).7-Hydroxy aristolochic acid A(6):UV k max:224,271,318,384nm;ESMSÀve mode,m/z356(MÀH)À.Aristolochic acid D(7):UV k max:224,243,333,408nm;ESMS m/z358(M+H)+.Compound(21)18:UV k max:214,242,258,294,328,398nm;ESMS:m/z280 (M+H)+;1H NMR(DMSO-d6)d:10.72(s,NH),10.2(s,–OH),8.03(d,J=15Hz,5-H),7.63(s,2-H),7.37(t,J=15Hz,6-H),7.36(s,9-H),7.06(d,J=15Hz,7-H),6.46(s,12-H2).13C NMR(DMSO-d6)ppm:168.1(11-C),153.8(8-C),148.8(3-C),147.1(4-C),134.0(10-C),125.8(6-C),125.3(4b-C),125.3(10a-C),123.2(8a-C),119.3(1-C),117.5(5-C),112.3(7-C),111.3(4a-C),105.4(2-C),103.2 (12-C),98.7(9-C).Compound(16)16:UV k max:225,239,258,295,329,394nm;ESMS:m/z294 (M+H)+;1H NMR(DMSO-d6)d:10.67(s,NH),8.22(d,J=16Hz,5-H),7.70(s,2-H),7.50(t,J=16Hz,6-H),7.35(s,9-H),7.20(d,J=16Hz,7-H),6.48(s,12-H2),4.0(s,13-H3).13C NMR(DMSO-d6)ppm:168.1(11-C),155.3(8-C),148.8(3-C),147.1(4-C),134.7(10-C),125.7(6-C),125.0(11a-C),124.8(4b-C),124.0(10a-C),119.3(1-C),118.7(5-C),111.0(4a-C),108.3(7-C),105.7(2-H),103.3(12-C),97.9(9-C)add–OCH3value.Compound(29):ESMS:m/z316(M+H)+;1H NMR(DMSO-d6)d:9.12(d, J=16Hz,5-H),7.52(t,J=16Hz,6-H),7.50(s,2-H),7.22(d,J=16Hz,7-H),3.92 (s,–OCH3),13C NMR(DMSO-d6)ppm:NOE from–OCH3to proton doublet at d7.22due to7-H and no NOE from–OCH3.All the new compounds were purified by HPLC and identified by MS.V.R.Hegde et al./Bioorg.Med.Chem.Lett.20(2010)1384–13871387。
中国天气预报代码大全
中国天气预报代码大全阿巴嘎旗 CHXX0243 阿城 CHXX0001爱辉CHXX0174阿合奇 CHXX0210阿拉尔 CHXX0212 阿勒泰 CHXX0196安达CHXX0187敖汉旗 CHXX0002安康CHXX0394 安宁CHXX0003 安庆CHXX0452鞍山 CHXX0004安顺CHXX0005 安阳CHXX0269 安县CHXX0182 巴楚 CHXX0211百灵庙CHXX0247 班戈CHXX0324 百色CHXX0488 白银 CHXX0006巴仑台CHXX0204 保定CHXX0308 宝鸡CHXX0387 宝清 CHXX0188保山CHXX0370 包头CHXX0007 巴中CHXX0348 巴塘 CHXX0352巴音毛道 CHXX0225 巴音布鲁克 CHXX0206 北塔山 CHXX0201北海CHXX0499 北京CHXX0008 蚌埠CHXX0444 本溪 CHXX0296毕节CHXX0418 彬县CHXX0439 波阳CHXX0009 博克图 CHXX0287长岛CHXX0312 长白CHXX0299 长春CHXX0010 常德 CHXX0416昌吉CHXX0011 长岭CHXX0277 长平CHXX0012 长沙 CHXX0013常熟CHXX0014 长汀CHXX0472 常州CHXX0015 朝阳 CHXX0294承德CHXX0302 成都CHXX0016 成山头CHXX0314 郴州 CHXX0435赤峰CHXX0286 重庆CHXX0017 楚雄CHXX0373 达县 CHXX0400大柴旦 CHXX0230 大陈岛 CHXX0464 达拉特旗 CHXX0018 大理 CHXX0371大连CHXX0019 丹东CHXX0306 单县CHXX0505 稻城 CHXX0357Daodi CHXX0020 Daolin CHXX0021 Darlag CHXX0336 大同 CHXX0251大通CHXX0022 大悟CHXX0347 大兴CHXX0023 德格 CHXX0344德令哈 CHXX0231 丁青 CHXX0342 堆龙德庆 CHXX0360 定海 CHXX0455定陶CHXX0320 定西CHXX0024 定县CHXX0025 东方 CHXX0504东沙岛CHXX0503 东升CHXX0255 东台CHXX0445 都兰 CHXX0235敦化CHXX0284 敦煌CHXX0223 多伦CHXX0285 独山 CHXX0432伊金霍洛旗CHXX0220 峨眉山CHXX0359 恩施 CHXX0406二连浩特 CHXX0240 房县 CHXX0395 凤城CHXX0026 奉节 CHXX0401丰宁CHXX0292 丰台CHXX0027 佛冈CHXX0483 佛山 CHXX0028扶绥CHXX0030 福鼎CHXX0469 富锦CHXX0185 抚顺 CHXX0029阜阳(富阳) CHXX0442 富蕴 CHXX0197 福州CHXX0031 刚察 CHXX0232甘谷CHXX0032 赣榆CHXX0438 赣州CHXX0436 高要 CHXX0491高邑CHXX0033 甘孜CHXX0345 耿马CHXX0377 格尔木 CHXX0234贡嚘CHXX0034 珙县CHXX0035 拐子湖CHXX0222 广安 CHXX0036广昌CHXX0470 广华CHXX0396 广南CHXX0477 广州 CHXX0037贵定CHXX0038 桂林CHXX0434 桂平CHXX0489 贵阳 CHXX0039固始CHXX0443 固阳CHXX0040 海城CHXX0041 海口 CHXX0502海拉尔CHXX0175 海林CHXX0244 海伦CHXX0183 海宁 CHXX0042海晏CHXX0319 Haliut CHXX0246 哈密CHXX0219 汉沽 CHXX0043杭州CHXX0044 汉江CHXX0045 汉中CHXX0390 哈尔滨 CHXX0046河池CHXX0478 合川CHXX0047 合肥CHXX0448 合江 CHXX0048河南CHXX0337 河曲CHXX0256 河源CHXX0492 菏泽 CHXX0339和布克塞尔 CHXX0199 呼和浩特 CHXX0249 香港 CHXX0049和田CHXX0216 华山CHXX0388 淮阳CHXX0052 化德 CHXX0248桦甸CHXX0290 怀来CHXX0301 华家岭CHXX0239 黄山 CHXX0453黄陂CHXX0050 黄石CHXX0051会理CHXX0366 惠民 CHXX0311会泽CHXX0367 惠州CHXX0053 呼兰CHXX0054 虎林 CHXX0194呼玛CHXX0172 霍山CHXX0447 胡四台CHXX0055 湖州 CHXX0056吉兰太 CHXX0252 扎鲁特旗 CHXX0275 集安 CHXX0425 江城 CHXX0384江津CHXX0057 江陵CHXX0408 江门CHXX0058 建阳 CHXX0059胶南CHXX0060 焦县CHXX0061 嘉兴CHXX0062 介休 CHXX0268吉林CHXX0063 济南CHXX0064 景德镇CHXX0457 静海 CHXX0065精河CHXX0202 景洪CHXX0380 靖远CHXX0066 济宁 CHXX0250锦州CHXX0067 九江CHXX0068 九龙CHXX0361 酒泉 CHXX0226九台CHXX0069 九仙山CHXX0475 久镇CHXX0070 鸡西 CHXX0193朱日和 CHXX0245 句容 CHXX0071 哈巴河CHXX0195 开封 CHXX0072开阳 CHXX0073 康定 CHXX0358 克拉玛依CHXX0200 喀什 CHXX0074克山 CHXX0181 King's Park CHXX0170 库尔勒 CHXX0209库伦旗CHXX0075 宽甸CHXX0305 昆明CHXX0076 昆阳 CHXX0077库车CHXX0208 澜沧CHXX0379 阆中CHXX0399 兰西 CHXX0078兰州CHXX0079 冷湖CHXX0227 乐亭CHXX0307 拉萨 CHXX0080乐至CHXX0329 连县CHXX0481 梁平CHXX0405 连平 CHXX0484辽阳CHXX0081 利津CHXX0365 临沧CHXX0378 临东 CHXX0276零陵CHXX0429 陵县CHXX0310 临海CHXX0463 临河 CHXX0253临江CHXX0297 临潼CHXX0082 林西CHXX0281 灵石 CHXX0264丽水CHXX0461 理塘CHXX0353 浏阳CHXX0083 柳州 CHXX0479溧阳CHXX0450 龙口CHXX0313 龙里CHXX0084 龙州 CHXX0494庐山CHXX0456 漯河CHXX0085 罗甸CHXX0431 洛阳 CHXX0086卢氏CHXX0389 泸水CHXX0087 吕泗CHXX0446 泸溪 CHXX0376泸州CHXX0088 澳门CHXX0512 麻城CHXX0403 玛多 CHXX0335玛纳斯 CHXX0089 满都拉 CHXX0242 茫崖CHXX0217 茂名 CHXX0090马鬃山CHXX0221 梅县CHXX0486 眉山CHXX0091 勐腊 CHXX0383蒙山CHXX0480 孟州CHXX0092 蒙自CHXX0385 绵阳 CHXX0351民和CHXX0093 民勤CHXX0229 闽清CHXX0094 米泉 CHXX0095密云CHXX0096 漠河CHXX0171 牡丹江CHXX0278 那曲 CHXX0325南昌CHXX0097 南城CHXX0465 南充CHXX0098 南京 CHXX0099南宁CHXX0100 南平CHXX0471 南沙岛CHXX0511 南通 CHXX0101南县CHXX0102 南阳CHXX0391 南岳CHXX0423 那坡 CHXX0487那仁宝力格 CHXX0241 内江 CHXX0103 嫩江 CHXX0177New Kowloon CHXX0104 牛庄CHXX0105 Nyingchi CHXX0356鄂托克旗 CHXX0254 帕里 CHXX0330 平凉CHXX0270平潭CHXX0476 平武CHXX0350 平遥CHXX0106 平阴 CHXX0107皮山CHXX0215 勃力CHXX0108 泊头CHXX0309 蒲城 CHXX0468蒲口 CHXX0109 恰卜恰 CHXX0343 前郭尔罗斯 CHXX0190Qijiaojing CHXX0205 青岛 CHXX0110 清江CHXX0111 青龙 CHXX0303清远CHXX0289 钦州CHXX0498 琼海CHXX0506 齐齐哈尔 CHXX0112奇台CHXX0113 渠县CHXX0460 泉州CHXX0114 曲麻莱 CHXX0333日照CHXX0322 榕江CHXX0433 瑞丽CHXX0375 若尔盖 CHXX0338若羌CHXX0214 桑植CHXX0410 珊瑚岛CHXX0509 三水 CHXX0426色达CHXX0346 上蔡CHXX0115 上川岛CHXX0501 上海 CHXX0116尚志CHXX0192 汕头CHXX0493 汕尾CHXX0496 韶关 CHXX0482邵武CHXX0466 绍兴CHXX0117 邵阳CHXX0422 沙市 CHXX0118嵊泗CHXX0454 深县CHXX0458 沈阳CHXX0119 深圳 CHXX0120射阳CHXX0441 石拐CHXX0121 石家庄CHXX0122 石楼 CHXX0123石浦CHXX0459 狮泉河CHXX0323 双城CHXX0124 沭阳 CHXX0125思茅CHXX0381 思南CHXX0420 四平CHXX0283 索县 CHXX0341松潘 CHXX0349 石炭井 CHXX0126 绥芬河CHXX0279 绥宁 CHXX0127孙吴CHXX0178 塔城CHXX0198 塔河CHXX0128 泰山 CHXX0316泰来CHXX0186 太原CHXX0129 塘沽CHXX0130 唐山 CHXX0131腾冲CHXX0369 天冈CHXX0132 天津CHXX0133 天水 CHXX0386铁岭 CHXX0134 铁干里克 CHXX0213 铁力CHXX0328 通道 CHXX0427通河CHXX0191 通辽CHXX0282 图里河CHXX0173 托托河 CHXX0331吐鲁番CHXX0207 Uliastai CHXX0189 。
Perkins 1006-6 FED CC T6.60CC 6周期柴油发动机说明书
APPLICATION: Forklifts: Linde Unknown (YB50528);Sweepers: Johnston Unknown (YE70301);(10)Used When Taper Press Tooling Is Not Available (Machine Taper After Boring To Size) (11)Used With Proper Taper Press ToolingPK-365-J 5/1/2010QTY ITEM # DESCRIPTION LETTERED ITEMSINCLUDED IN KIT6 171554 Piston Assembly (Grade J-L / 2.7622" Compression Dist)6 171555 Piston Assembly (Grade F-H / 2.7677" Compression Dist)6 171367 Cylinder Liner (Flange/Finished/Fire Dam/4.1035" OD) (1)6 171366 Cylinder Liner (Flange/Semi-Finished/FD/4.1055" OD) (2)6 171468 005 Liner Shim6 171281 Ring Set (1-3.5K 1-2.5 1-4.0)6 271261 STD Rod Bearing (Locating Tangs For Notched Rods)6 271262 .010 Rod Bearing (Locating Tangs For Notched Rods)6 271263 .020 Rod Bearing (Locating Tangs For Notched Rods)6 271264 .030 Rod Bearing (Locating Tangs For Notched Rods)1 271191 STD Main Set, wo/Thrust Washers: "YE" Build Lists (3)1 271192 .010 Main Set, wo/Thrust Washers: "YE" Build Lists (3)1 271193 .020 Main Set, wo/Thrust Washers: "YE" Build Lists (3)1 271194 .030 Main Set, wo/Thrust Washers: "YE" Build Lists (3)1 271119 STD Thrust Washer Set (Offset Lug)1 271125 .007 Thrust Washer Set (Offset Lug)1 271126 .010 Thrust Washer Set (Offset Lug)1 371451 Head Gasket Set "Head Gasket - 371324"1 371219 Valve Cover Gasket (Aluminum Cover)1 371148 Valve Cover Gasket (Composite Cover)12 371143 Valve Seal1 371454 Lower Gasket Set wo/Seals: (5) (No Compressor)1 371461 Lower Gasket Set wo/Seals: (6) (Compressor Gear Case)1 371393 Timing Cover Gasket: (5) (No Compressor)1 371462 Timing Cover Gasket: (6) (Compressor Gear Case)1 371181 Pan Gasket Set (.032" Composite) "Pan Gkt Only - 371182"1 371362 Pan Gkt, Optional For Stressed Pan (.048" Perf Metal Core)1 371146 Front Crank Seal (Viton Lip Type) (7)1 371145 Rear Crank Seal, Thru U764751H (Viton Lip Type) (8)1 371297 Rear Crank Seal & Housing, After U764751H (9)6 271244 Pin Bush, Butt Split Rod (Straight / 1.563" Pin / 1.660" OD)6 271198 Pin Bush, Fractured Rod (Straight/1.563" Pin/1.698" OD) (10)6 271289 Pin Bush, Fractured Rod (Taper/1.563" Pin/1.698" OD) (11)1 271127 Cam Bearing (Finished ID)12 771368 Rod Capscrew (Doweled Flat Butt Split/1/2 x 2.766 Hex Hd) 12 771323 Rod Capscrew (Fractured Split / 7/16 x 2.580 12 Pt Head)6 771352 Connecting Rod (1.563" Pin)1 771343 Head Bolt Kit (32 Bolts)(1).010 OS Finished Liner - 171368 (2).020 OS Semi-Finished Liner - 171511(3)YB50528 Uses 271311 STD / 271312 .010 / 271313 .020 / 271314 .030 (5)YE70301 (6)YB50528 (7)Wear Sleeve - 301115(8)Lip Seal Housing Gasket - 371187 / Wear Sleeve - 301143 (9)Wear Sleeve - 371366Sweepers: Johnston Unknown (YE70301);(12)Adjusting Screw-471226 / Lock Nut - 571139(13)Rocker Arm Shaft Snap Ring - 471228PK-365-J(14)Includes 2 Bushings - 5711445/1/2010QTY ITEM # DESCRIPTION LETTERED ITEMSINCLUDED IN KIT1 979527 Camshaft Kit: "YE" Build Lists C1 979526 Camshaft Kit: YB50528 C1 979164 Valve Train Kit (High Speed / Dual Springs)V1 571242 Camshaft: YE Build Lists "M12 x 45MM Cam Bolt - 771363" C1 571183 Camshaft: YB50528 "M12 x 45MM Cam Bolt - 771363" C1 271249 Thrust Washer12 571123 Tappet C C6 6 471129 471116 Exhaust Valve (45º / 37.5MM Hd Dia) Intake Valve (45º / 45.0MM Hd Dia) V V6 471132 Exhaust Guide V6 471131 Intake Guide V12 471144 Outer Valve Spring (8 Coils / 1.8" Free Length) V12 471143 Inner Valve Spring (9 Coils / 1.7" Free Length) V12 471229 Spring Seat (Stepped/.640" ID)24 471146 Keeper (Half) V6 471288 Exhaust Seat (1.290 x 1.681 x .374 Stepped Top)6 471289 Intake Seat (45º / 1.584x2.019x.285)6 471224 LH Rocker Arm (Adj Screw & Lock Nut Not Included) (12)6 471225 RH Rocker Arm (Adj Screw & Lock Nut Not Included) (12)1 471345 Rocker Arm Shaft (13) "Includes 471176 Plugs"1 571171 Cam Gear (Steel / 56 Teeth)1 571131 Crank Gear (28 Teeth / 1.632" Wide)1 571163 Idler Gear (Steel / 63 Teeth) (14)12 571117 Push Rod1 671153 Oil Pump1 671195 Oil Pump Idler Gear "Includes Bush - 571124"1 671174 Relief Valve Assembly: YE703011 671196 Relief Valve Assembly: YB505286 671157 Piston Cooling Jet6 671158 Check Valve1 671198 Oil Cooler: Early (7 Plate/Vertical Studs)1 671173 Oil Cooler: Late (8 Plate/Angled Studs)1 771139 Crank Kit: YE Build Lists (Notched Rod / Full Groove Mains)1 771175 Crank Kit: YB50528 (Notched Rod / Half Groove Mains)1 771443 Cylinder Head Asb, 45º Intake (Includes Valves & Springs)1 771436 Expansion Plug Kit (22 Head & Block Plugs)2 871138 Thermostat (2.125" / Bypass)1 871294 Water Pump: YE703011 871163 Water Pump: YB505281 871274 Bypass Hose Kit。
专业名称及类码
专业代码专业名称AB0101 马、恩、列、斯思想研究AB0102 毛泽东思想邓小平理论研究AB0103 马克思主义发展史AB0104 科学社会主义AB0105 世界社会主义运动史AB0106 国外马克思主义研究AB0107 马克思主义哲学AB0108 科学技术哲学AB0109 中国哲学AB0110 东方哲学史AB0111 西方哲学史AB0112 现代外国哲学AB0113 逻辑学AB0114 伦理学AB0115 美学AB0116 哲学其他学科AB0201 宗教学理论AB0202 无神论AB0203 原始宗教AB0204 古代宗教AB0205 佛教AB0206 基督宗教AB0207 伊斯兰教AB0208 道教AB0209 印度教AB0210 犹太教AB0211 外国其他宗教AB0212 神道教AB0213 中国民间宗教与民间信仰AB0214 中国少数民族宗教AB0215 当代宗教AB0216 宗教学其他学科AC0101 英语-留学国别1为美国AC0102 英语-留学国别1为加拿大AC0103 英语-留学国别1为英国AC0104 英语-留学国别1为澳大利亚AC0105 英语-留学国别1为其他国家AC0201 德语-德语国家AC0301 法语-法语国家AC0401 日语-留学国别1为日本AC0501 俄语-俄语国家AC0601 其他语种-其他AD0101 音乐AD0201 戏剧AD0202 电影AD0205 戏曲AD0203 舞蹈AD0204 广播电视文艺AD0301 美术AD0302 工艺美术AD0303 书法AD0206 摄影AD0304 艺术学其他学科AE0101 史学史AE0102 史学理论AE0103 历史文献学AE0104 中国通史AE0111 中国古代史AE0112 中国近代史、现代史AE0113 世界通史AE0114 亚洲史AE0105 非洲史AE0106 美洲史AE0107 欧洲史AE0108 澳洲、大洋洲史AE0109 专门史AE0110 历史学其他学科AE0201 考古理论AE0202 考古学史AE0203 考古技术AE0204 中国考古AE0205 外国考古AE0206 专门考古AE0207 考古学其他学科AL0101 政治学理论AL0102 政治制度AL0103 行政学AL0104 国际政治学AL0105 政治学其他学科AF0101 理论法学AF0102 刑事法学AF0201 民法经济法学AF0301 国际法学AF0103 法学其他学科AG0101 社会学史AG0102 社会学理论AG0103 社会学方法AG0104 实验社会学AG0105 数理社会学AG0106 应用社会学AG0107 比较社会学AG0108 社会地理学AG0109 文化社会学AG0110 历史社会学AG0111 科学社会学AG0112 经济社会学AG0113 军事社会学AG0114 社会心理学AG0115 公共关系学AG0116 社会人类学AG0117 组织社会学AG0118 发展社会学AG0119 福利社会学AG0120 人口学AG0121 社会学其他学科AG0201 军事学AH0101 民族学文化人类学AH0102 民俗学AH0103 藏学突厥学蒙古学朝鲜学AH0104 民族文物及博物馆学AH0105 世界民族研究AH0106 民族社会学AH0107 民族经济学AH0108 民族政治学AH0109 民族学其他学科AI0101 新闻理论AI0102 新闻史AI0103 新闻业务AI0104 新闻事业经营管理AI0105 广播与电视AI0106 传播学AI0107 新闻学与传播学其他学科AJ0101 教育史AJ0102 教育学原理AJ0103 教学论AJ0104 德育原理AJ0105 教育社会学AJ0106 教育心理学AJ0107 教育经济学AJ0108 教育统计学AJ0109 教育管理学AJ0110 比较教育学AJ0111 教育技术学AJ0112 军事教育学AJ0113 学前教育学AJ0114 普通教育学AJ0115 高等教育学AJ0116 成人教育学AJ0117 职业技术教育学AJ0118 特殊教育学AJ0119 教育学其他学科AK0101 体育史AK0102 体育理论AK0103 运动生物力学AK0104 运动生理学AK0105 运动心理学AK0106 运动生物化学AK0107 体育保健学AK0108 运动训练学AK0109 体育教育学AK0110 武术理论与方法AK0111 体育管理学AK0112 体育经济学AK0113 体育科学其他学科BA0101 数学史BA0102 数理逻辑与数学基础BA0103 数论BA0104 组合数学BA0105 非标准分析BA0201 拓扑学BA0202 代数学BA0203 代数几何学BA0301 离散数学BA0302 几何学BA0303 常微分方程BA0304 偏微分方程BA0305 积分方程BA0306 动力系统BA0106 数学分析BA0307 函数论BA0308 泛函分析BA0401 计算数学BA0402 应用统计数学BA0403 数理统计学BA0404 概率论BA0405 运筹学BA0406 模糊数学BA0204 应用数学BA0205 数学其他学科BB0101 信息科学与系统科学基础学科BB0102 控制理论BB0103 系统学BB0104 系统工程方法论BB0105 系统评估与可行性分析BB0106 系统工程(信息科学与系统科学)BC0201 理论物理学BC0202 原子核物理学BC0203 高能物理学BC0204 计算物理学BC0101 电磁学BC0102 声学BC0103 热学BC0104 无线电物理BC0105 电子物理学BC0205 凝聚态物理学BC0206 等离子体物理学BC0207 光学BC0208 应用物理学BC0209 原子分子物理学BC0210 物理学史BC0211 物理学交叉学科BC0301 天文学史BC0302 天体演化学BC0303 天体生物学BC0304 天文学其他学科BC0305 天体力学BC0306 天体物理学BC0307 天体测量学BC0308 射电天文学BC0309 空间天文学BC0310 天体化学BC0311 星系与宇宙学BC0312 恒星与银河系BC0313 太阳与太阳系BD0101 物理化学BD0102 化学物理学BD0103 高分子化学与物理BD0104 化学生物学BD0105 有机化学BD0201 分析化学BD0202 无机化学BD0203 核化学BD0204 化学史BD0205 应用化学BD0206 化学其他学科BF0101 地球科学史BF0102 地球科学其他学科BF0201 水文学BF0202 海洋科学BF0103 大地测量学BF0104 地图学BF0105 固体地球物理学BF0106 空间物理学BF0301 地球化学BF0302 地质学BF0401 大气科学BG0101 生物进化论BG0102 生物数学BG0103 生物物理学BG0104 病毒学BG0201 微生物学BG0202 细胞生物学BG0203 发育生物学BG0105 遗传学BG0106 生物工程BG0107 生物化学BG0108 分子生物学BG0109 放射生物学BG0301 神经生物学BG0302 生理学BG0303 动物学BG0401 人类学BG0402 昆虫学BG0403 植物学BG0501 生态学BG0502 生物学其他学科BG0601 心理学CA0101 一般力学与力学基础CA0102 固体力学CA0103 流体力学CA0104 工程力学(力学)CB0101 工程数学CB0102 工程控制论CB0103 工程力学(工程与技术科学基础学科)CB0104 工程物理学CB0105 计量学CB0106 工程图学CB0107 工程地质学CB0108 工程水文学CB0109 勘查技术CB0110 工程仿生学CB0111 工程心理学CB0112 标准化科学技术CB0113 工程通用技术CB0114 工业工程学CB0115 工程与技术科学基础学科其他学科CC0101 大地测量科学技术CC0102 摄影测量与遥感技术CC0103 地图制图与地理信息系统技术CC0104 工程测量技术CC0105 海洋测绘技术CC0106 测绘仪器技术CC0107 测绘科学技术其他学科CD0101 无机非金属材料CD0201 有机高分子材料CD0301 材料合成与加工工艺CD0401 材料表面与界面CD0402 复合材料CD0403 金属材料CD0404 材料科学CD0501 材料失效与保护CD0502 材料检测与分析技术CD0503 材料实验CD0504 材料科学与工程其他学科CE0101 矿山地质学CE0102 矿山测量CE0103 矿山设计CE0104 矿山地面工程CE0105 井巷工程CE0106 采矿工程CE0107 选矿工程CE0108 钻井工程CE0109 油气田井开发工程CE0110 石油、天然气储存与运输工程CE0111 矿山机械工程CE0112 矿山电气工程CE0113 采矿环境工程CE0114 矿山安全CE0115 矿山综合利用工程CE0116 矿山工程技术其他学科CF0101 冶金物理化学CF0102 冶金反应工程CF0103 冶金原料与预处理CF0104 冶金热能工程CF0105 冶金技术CF0106 钢铁冶金CF0107 有色金属冶金CF0108 轧制CF0109 冶金工程技术其他学科CF0110 冶金机械及自动化CG0101 机械史CG0102 机械学CG0103 机械设计CG0201 机械制造工艺与设备CG0202 刀具技术CG0203 机床技术CG0301 仪器仪表技术CG0302 流体传动与控制CG0303 机械制造自动化CG0204 专用机械工程CG0205 机械工程其他学科CH0101 工程热物理CH0102 热工学CH0103 动力机械工程(工程热物理)CH0201 动力机械工程(热工学)CH0202 电气工程CH0203 动力与电气工程其他学科CI0101 能源化学CI0102 能源地理学CI0103 能源计算与测量CI0104 储能技术CI0105 节能技术CI0106 一次能源CI0107 二次能源CI0108 能源系统工程CI0109 能源科学技术其他学科CJ0101 辐射物理与技术CJ0102 核探测技术与核电子学CJ0103 放射性计量学CJ0104 核仪器、仪表CJ0105 核材料与工艺技术CJ0106 粒子加速器CJ0107 裂变堆工程技术CJ0108 核聚变工程技术CJ0109 核动力工程技术CJ0110 同位素技术CJ0111 核爆炸工程CJ0112 核安全CJ0113 乏燃料后处理技术CJ0114 辐射防护技术CJ0115 核设施退役技术CJ0116 放射性三废处理、处置技术CJ0117 核科学技术其他学科CKCL 电子科学技术、信息与通讯工程、控制科学与工程CK0101 物理电子学CK0102 微电子学与固体电子学CK0103 光电子学与激光技术CK0104 电路与系统CK0105 电磁场与微波技术CK0106 电子科学与技术其他学科CK0201 广播与电视工程技术CK0202 信号与信息处理CK0301 通信与信息系统CK0302 信息与通讯工程其他学科CK0401 控制理论与控制工程CK0403 导航、制导与控制CK0501 模式识别与智能系统CK0502 检测技术与自动化装置CK0503 控制科学与工程其他学科CM0101 计算机科学技术基础学科CM0102 计算机软件CM0201 计算机系统结构CM0202 计算机科学技术其他学科CM0301 人工智能CM0401 信息安全CM0501 计算机应用技术CM0502 计算机网络技术CM0503 计算机工程CN0101 化学工程基础学科CN0102 化工测量技术与仪器仪表CN0103 化工传递过程CN0104 化学分离工程CN0105 化学反应工程CN0106 化工系统工程CN0107 化工机械与设备CN0108 无机化学工程CN0109 有机化学工程CN0110 电化学工程CN0111 高聚物工程CN0112 煤化学工程CN0113 石油化学工程CN0114 精细化学工程CN0115 造纸技术CN0116 毛皮与制革工程CN0117 制药工程CN0118 生物化学工程CN0119 化学工程其他学科CO0101 纺织材料CO0102 化学纤维CO0103 纺织技术CO0104 染整技术CO0105 服装技术CO0106 纺织机械与设备CO0107 纺织科学技术其他学科CP0101 食品基础学科(含食品化学食品营养食品安全食品分析与CP0201 食品工程CP0202 食品机械与包装CP0203 食品储藏与资源开发CP0204 食品工业企业管理学CP0205 食品贸易与文化CP0102 食品科学技术其他学科CQ0102 土木建筑结构CQ0103 建筑史CQ0104 土木建筑工程基础学科CQ0105 土木建筑工程测量CQ0106 土木建筑工程设计CQ0107 土木建筑工程施工CQ0108 土木建筑工程其他学科CQ0109 建筑材料CQ0110 土木工程机械与设备CQ0111 市政工程CQ0112 建筑经济学CR0101 水利水电工程CR0102 水文学及水资源CR0103 水工结构工程CR0104 水利学与河流动力学CR0105 港口、海岸与近海工程CR0106 水利工程其他学科CS0101 道路工程CS0102 公路运输CS0103 铁道工程CS0104 铁路运输CS0201 水路运输CS0202 船舶、舰船工程CS0301 航空运输CS0401 交通运输系统工程CS0402 交通运输安全工程CS0403 交通运输工程其他学科CT0101 航空、航天科学技术基础学科CT0102 航空器结构与设计CT0103 航天器结构与设计CT0104 航空、航天推进系统CT0105 飞行器仪表、设备CT0106 飞行器控制、导航技术CT0107 航空、航天材料CT0108 飞行器制造技术CT0109 飞行器试验技术CT0110 飞行器发射、飞行技术CT0111 航天地面设施、技术保障CT0112 航空、航天系统工程CT0113 航空、航天科学技术其他学科CU0101 环境科学与技术CU0102 环境规划与管理CU0103 环境工程CU0104 环境科学其他学科CV0101 安全科学技术基础学科CV0102 安全学CV0103 安全工程技术CV0104 职业卫生工程CV0105 安全管理工程CV0106 安全科学技术其他学科DA0101 人体解剖学DA0102 人体组织胚胎学DA0103 病理学DA0201 医学寄生虫学DA0202 医学微生物学DA0301 药理学(基础医学)DA0401 人体免疫学DA0501 医学生物化学DA0601 放射医学DA0602 医学细胞生物学DA0603 人体生理学DA0604 病理生理学DA0605 医学遗传学DA0606 生物医学工程学DA0701 医学实验动物学DA0702 医学心理学DA0703 医学统计学DA0704 基础医学其他学科DB0101 保健医学(大外科)DB0102 康复医学(大外科)DB0103 麻醉学DB0104 护理学(大外科)DB0105 临床医学其他学科(大外科)DB0106 急诊及危重病医学(大外科)DB0107 临床诊断学(大外科)DB0401 耳鼻咽喉科学DB0201 口腔医学DB0301 眼科学DB0402 外科学DB0501 影像医学与核医学(大外科)DB0502 肿瘤学(大外科)DB0601 内科学(大外科)DB0602 神经病学(大外科)DB0603 精神病学(大外科)DB0701 妇产科学DB0702 儿科学(大外科)DB0801 皮肤病学(大外科)DB0802 性医学(大外科)DC0101 保健医学(大内科)DC0102 康复医学(大内科)DC0103 护理学(大内科)DC0104 临床医学其他学科(大内科)DC0105 急诊及危重病医学(大内科)DC0106 临床诊断学(大内科)DC0201 影像医学与核医学(大内科)DC0202 肿瘤学(大内科)DC0301 内科学(大内科)DC0302 传染病学(大内科)DC0303 神经病学(大内科)DC0304 精神病学(大内科)DC0401 儿科学(大内科)DD0101 毒理学DD0201 消毒学DD0202 流行病学DD0203 传染病学(预防医学与公共卫生学)DD0301 职业病学DD0302 地方病学DD0303 营养学DD0304 卫生检验学DD0305 食品卫生学DD0306 环境卫生学DD0307 劳动卫生学DD0308 放射卫生学DD0309 卫生工程学DD0401 卫生经济学DD0402 社会医学DD0403 儿少卫生学DD0404 妇幼卫生学DD0405 健康教育学DD0406 卫生事业管理学DD0407 预防医学与卫生学其他学科DE0101 军事医学DE0102 特种医学DE0103 军事医学与特种医学其他学科DF0101 药物化学DF0102 生物药物学DF0103 微生物药物学DF0104 放射性药物学DF0105 药剂学DF0106 药理学(药学)DF0107 药物管理学DF0108 药学其他学科DG0101 中医学DG0102 民族医学DG0103 中西医结合医学DG0104 中药学DG0105 中医学与中药学其他学科EA0701 农业史EA0101 农业基础学科EA0201 农艺学EA0301 园艺学EA0401 土壤学EA0501 植物保护学EA0601 农业工程EA0702 农学其他学科EB0101 林业基础学科EB0102 林木遗传育种学EB0103 森林培育学EB0104 森林经理学EB0105 森林保护学EB0106 野生动物保护与管理EB0107 防护林学EB0108 经济林学EB0109 园林学EB0110 林业工程EB0111 森林统计学EB0112 林业经济学EB0113 林学其他学科EC0101 临床兽医学EC0102 基础兽医学EC0103 预防兽医学EC0201 动物遗传EC0202 繁育学EC0203 动物生产学EC0204 动物营养学ED0101 水产学基础学科ED0102 水产增殖学ED0103 水产养殖学ED0104 水产饲料学ED0105 水产保护学ED0106 捕捞学ED0107 水产品贮藏与加工ED0108 水产工程学ED0109 水产资源学ED0110 水产经济学ED0111 水产学其他学科FA0101 管理思想史FA0102 管理理论FA0103 管理计量学、管理经济学FA0104 部门经济管理FA0105 管理学其他学科FA0106 管理心理学FA0107 未来学FA0201 科学学与科技管理FA0301 企业管理FA0401 行政管理FA0501 管理工程FA0601 人力资源开发与管理FA0701公共管理学FB0101 世界经济学FB0201 技术经济学FB0202 产业经济学FB0301 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WEKA Cryogenic Components紧凑型低温阀门说明书
Compact cryogenic valves for liquefied hydrogen fuelled carsDr. David Brütsch, Fridolin HoldenerWEKA AG, Schuerlistrasse 8, CH-8344 BaeretswilABSTRACT:Based on the long-term experience WEKA has developed a compact valve with integrated pneumatic actuator for extreme low temperature applications. Due to the compact design, these valves are preferred for mobile use. The valves can handle a temperature gradient of over 250 degrees and guarantee a perfect tightness over the whole temperature range. To prevent freezing at the warm end of the valve, WEKA designed a compound spindle of extremely low heat load, made in composite material. For further compactness a valve block design will be developed.KEYWORDS: compact cryogenic valve, liquid hydrogen fuelled car, cryogenic automotive tank1. IntroductionWEKA Cryogenic Components provide optimal solutions for handling of low-temperature liquefied gases under extreme operating conditions. Cryogenic respectively cold comes from the Greek word ?????. Generally "cryogenic" refers to the temperature range below about 120K (-153 °C). WEKA Cryogenic Components are generally used in applications involving liquid and gaseous media below 20K (-253 °C). Cryogenic technology is used for cooling of superconducting solenoids and acceleration cavities in high energy physics and in fusion research. Cryogenic pumps generate ultrahigh vacuums. Liquid hydrogen is used as fuel for rockets and more and more as energy source. Cryogenic distillation processes are used for the production and storage of Helium and Hydrogen as well as for Oxygen, Nitrogen and Argon. Due to its physical properties Helium (He) in the gas, liquid or super fluid state is the most used cooling fluid with WEKA Cryogenic Components. The normal boiling point of Helium is 4.2K. Liquid hydrogen (LH2, normal boiling point at 20K) has been used as fuel in space vehicles, and is now drawing attention as an alternative energy source as well as for fuelling automobiles. Until this moment WEKA has delivered more than 2’500 cryogenic valves (with pressures up to 600bar). About 500 valves are used in the liquid hydrogen supply chain. Also used are WEKA Cryogenic Components with gases like Oxygen (O2, normal boiling point at90K), Argon (Ar, normal boiling point at 87K), Air, Nitrogen (N2, normal boiling point at 77K) and Hydrogen (H2,) as well as for rare gases like Xenon (Xe), Krypton (Kr) and Neon (Ne).2. WEKA standard cryogenic valvesThe design of a standard cryogenic valve is particularly intended for the employment in He- and H2-systems. These valves have to meet specific requirements which were the base for our new development of compact cryogenic valves.Keeping in mind that 1W cooling capacity at 4.5K has a power demand of 200...2000W the entire equipment (valves, connecting tubes, heat exchangers, sensors, etc.) will be placed into an insulation vacuum with a final pressure of p < 1*10-4mbar. Reducing the cooling down time of such a system means mass-poor design of the valves, e.g. minimized thickness of walls. Choosing the right size of a valve may also affect the efficiency of the whole system.Today, cryogenic systems are designed for continuous operation. Liquefaction or cooling plants are turned off only for planned revisions. Causing high costs, the complete warming up of a plant is avoided if possible. Therefore, cryogenic valves must offer a high reliability with a minimum of maintenance effort. E.g. for changing the seat seal or the control plug the valve stem has to be withdrawn through the housing, in order not to destroy the vacuum insulation.Frequently applied dimensions are from DN2 to DN200 where “DN” means diameter nominal and the number indicates the diameter of the valve bore in "mm". Primarily the size of the valve bore and valve travel determines the flow characteristic of the valve. A second important factor is the size and the design of the volume after the valve bore (outlet side). Reducing the flow resistance in a valve means minimal pressure drop. This can be achieved by a design with sufficient space after the bore for pressure increase. While selecting or purchasing cryogenic valves same nominal diameters from different suppliers are compared. The very central aspect is to compare the real valve bore and the associated Kv value (Cv = 1.16 * Kv). This will give you the best idea of the efficiency of a valve. WEKA standard cryogenic valves have a leading position in aspect of valve efficiency.So far normal operating pressures for cryogenic valves are from vacuum up to 25bar or 40bar. Beside these standard applications, WEKA has delivered also bellows sealed control valves for up to 630bar. In the future higher pressure valves will draw more attention because they enable smaller and more efficient plants and applications. Generally WEKA Cryogenic Valves are available asa) Bellows sealed valves followed by a security back-up sealing and a plugged leak test port. This high quality sealing system guarantees the highest tightness and safety under pressure and vacuum conditions. Preferably it will be used for low density fluids like He or H2. For high purity gases it is also recommended to use bellows sealed valves.b) Packing sealed valves with an elastomeric quad-ring for applications which have reduced requirements regarding tightness e.g. for fluids like Nitrogen (N2), Air, etc. However these valves could also be used for low density gases. Static seal to outside between valve body and bonnet and inset respectively is made with an elastomeric o-ring joint at the warm top end of the valve.The valve body is completely welded and manufactured from stainless steel (tubes and forged bars). Therefore the valves have a high operational reliability in continuous service and offer high protection against losing the insulation vacuum. Different applications require different body patterns. Standard for cryogenic cold boxes is the angle pattern (E-pattern). In transfer lines or pipes the globe or straight pattern is often used (see D-pattern or Z-pattern). On special request the Y-pattern is also available.E-Pattern D-pattern Z-pattern Y-patternFigure 1: Different body patternThe cryogenic length of a valve depends on the nominal diameter, the operating temperature and the space available in the installation. Standard cryogenic length’s are h = 600, 875, 1000 or 1300mm. If needed, other dimensions will be manufactured between the minimum (h = 300mm) up to max. 2000mm. Up to 1000mm the standard design is used. Considering the thermal expansion, valves with a cryogenic length longer than 1000mm need special compensating elements.The wall thickness of body and inset is optimized regarding minimal heat load by thermal conductivity and pressure and shut-off loads. For further reduction of heat loads, a thermal contact could be brazed to body pipe to contact a cooling shield.The valve seat is integrally machined into the valve body at the cold bottom end. It will be closed by a polymeric soft seal. The cardanic stem inset design guarantee seat tightness over the full temperature range. Some movement by thermal contraction of the piping could be compensated. Seal heads of valves size >= DN20 are spherical flexible joined to the inset. Smaller valves have elastically buckling spindle tubes. The seat tightness and flow control characteristic are separated by the design and adaptable to different specifications required.Figure 2: Flexible seal headGuiding elements in the warm and cold part of the valve are usually made from Aluminium-Bronze. Not by cold medium contacted areas could also consist of brass alloys. Best results regarding seat tightness and temperature stability will show thermoplastics like PTFE, PCTFE or PE UHMW. Also PEEK is very suitable in specific conditions. Designing the valve seat means also consider the special characteristics of theseplastics at ambient and cryogenic temperatures. Normally used for the O-ring seals are the elastomers NBR or FPM.Exact tolerances of the valve bore made it possible to use for both, on/off- (digital-) and control applications. For control valves appropriate standard flow plugs with either equal- % (1:100) or linear flow characteristics are available. Plugs with other special flow characteristics will be calculated and produced on request. Digitalvalves will be equipped with a flow trim which assures highest possible Kv value.0102030405060708090100relative valve travel (%)r e l a t i v e v a l v e f l o w c o e f f i c i e n t k v (%)Figure 3: Different flow characteristicsStandard cryogenic valves are equipped with a vacuum weld-in flange for cold-box mounting from the bottom side. On request we deliver valves without weld-in flange or valves with bigger flange diameter forassembling through the top plate. In special cases valves with vacuum jacket or with special vacuum flange assembly could be designed and manufactured.2.1 Valve ActuatorsWEKA Cryogenic Valves are normally equipped with pneumatic diaphragm actuators. Selectable are also manual drives or electric actuators. Actuator control accessories like limit switches, positioner, 3/2-way solenoid valves etc. could be selected according the specified valve function (control or on/off valve).with positioner with inductive sensors electric actuator manual driveFigure 4: Actuator typesThe actuator size and type is derived by the nominal valve size (DN), the specified operating or shut off pressure, the available energy (air pressure, power supply) and the plant control system. Particularly to consider are also the specifications about actuating time, fail function in case of energy loss and other restrictions like x-ray radiation or explosion proofed equipment.Due to large spatial expansion of cryogenic systems the newest developments of the field bus technology have an improved relevance for the process control. Communicating with the field devices the will be more and more important, e.g. WEKA valves are available with profibus or foundation fieldbus interface. This opens new perspectives for the operation and maintenance of a plant. Valves equipped with a digital electro-pneumatic position controller may receive over the field bus new operating parameters. On the other hand, number of valve movements, travel and actuating time could be logged. Deviations or special alarm limits could be processed by the master control.3. Compact cryogenic valves for LH2 fuelled carsThree years ago, an automotive OEM asked for compact valves with on/off function. Based on the long-term experience WEKA has developed a special valve with integrated pneumatic actuator for liquid hydrogen (LH2) application. The valves are built in a LH2 tank, where every tank needs two or three valves. The following figure shows the basic elements of such a tank. Two containers are separated by an insulation vacuum and super insulation carried by two suspensions. The pressure in the tank is controlled by an electrical heater and a relief valve. Extracting hydrogen normally happens in gaseous state; whileaccelerating or in other power consuming situations hydrogen will be extracted in liquid form.heat exchangerShieldOuter vessel(Shut off valves)Figure 5: Automotive tank for LH2Due to limited space the valves had to be very short. The actual valve design has an overall length of 300mm. Resulting fact is, that the valve has to handle a temperature gradient of over 200 degrees over a cryogenic length of 130mm. To prevent freezing at the warm end of the valve, WEKA designed a compound spindle of extremely low heat load, made in composite material.Furthermore reducing the evaporation rate is a goal of all tank manufacturers. Therefore the valve has to guarantee a perfect tightness over the whole temperature range. On one hand the valve is bellows sealed,on the other hand the soft-sealing head has a parabolic geometry.Pneumaticpiston actuatorSpring loaded cap(safety position)Weld-in flange forvaccuum insulationMinimized cryogeniclength h=130mmHousing with Z-patterninlet & outlet 90° rotatedFigure 6: Compact cryogenic valve for LH2Such valves have already been ordered by gas suppliers and/or distributors and automotive OEM’s. These compact valves – built in LH2 tanks – are at this moment in daily use. Several automobiles are driving with this valves; one of them has already logged more than 60,000km on the road.3.1 Energy less safety positionThe valve and in special the pneumatic actuator has an energy less safety position. In case of energy loss a preloaded spring will move the piston in the actuator and close the valve. In this closed position the valve is perfectly tight. Therefore only for opening a pneumatic actuation is needed. Two energy less positions could be designed by using a latching principle. In this case laterally arranged springs hold the valve spindle in two end positions.3.2 actuation principlesAs usually mounted on standard cryogenic valves the compact cryogenic valve has also a pneumatic actuator. The spindle is fixed to a piston which is hold in the closed position by a spring. On board of an automobile often the energy is available in electrical form. Therefore concepts are needed with electrical actuation or electro-hydraulic actuation. WEKA is testing hydraulic actuation systems for cryogenic valves. Big advantages are the compactness and the resulting actuation forces.3.3 integration aspectsOnboard of a car or a bus, the cryogenic valves usually are nearby the LH2 tank. From our point of view we do not see at the moment other insulating variants than the weld-in in a vacuum insulation. Therefore the valves are equipped with a weld-in flange and a withdrawal inset. Depending on space and geometric situation the valve has to be mounted either vertically or horizontally. Mounting a cryogenic valve horizontally means prevent the liquid medium to flow to the warm end of the valve. The existing design is adaptable to other mounting situations or customer specific needs. For further compactness the valves could be combined in one valve block. In the following picture a liquid hydrogen tank is shown with an attached valve box. Three valves are mounted in one weld’in flange and could be mounted as one pre-manufactured unit. The shown valves are actuated with a hydraulic fluid. Therefore the actuators could be designed very compact.Figure 7: Compact valve box unit attached to a tank4. ConclusionCompact cryogenic valves have some similar aspects compared with standard cryogenic valves. Regarding the minimized heat load highly relevant are the design and the manufacturing of the compound spindle. Completely welded housings guarantee a long-term stability of the vacuum insulation. In the future producing large series of valves may change the manufacturing method of the housings. Standards for cryogenic valve tightness in automotive area are to define. WEKA’s values of seat tightness and the measuring method are derived from the vacuum technology and satisfy our customers.The design and the manufactured compact valves have been proven in everyday use. Several automobiles are driving with this valves; one of them has already logged more than 60,000km on the road. Future developments will continuously improve the actual design and show the suitability for mass production. References:.Frey, H., Haefer, R.A., Tieftemperaturtechnologie, Hrsg.: Eder, F.X., VDI Verlag GmbH, Düsseldorf, 1981 Holdener, F., Ventile in der Kryotechnik in: DKV Tagungsbericht, 24. Jahrgang, Band 1, Deutscher Kälte- und Klimatechnischer Verein e.V., Hamburg, 1997, pages 85 - 94Holdener, F., Einsatz, Auslegung, Konstruktion und Fabrikation von Ventilen für die Kryotechnik, in: Dick, S., Kecke, H.J., (Hrsg.), Industriearmaturen 2000, Vulkan Verlag GmbH, Essen, 2000, pages 44 – 53 Wutz, M., Hermann, A., Walcher, W, Theorie und Praxis der Vakuumtechnik, 4. Auflage 1988, F. Vieweg & Sohn Verlagsgesellschaft mbH, Braunschweig, 1988。
CivilV介绍0302
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Civil MIDAS
Integrated Solution System For Bridge and Civil Structure
2007 版
分析 1.2 考虑P-Delta效应的施工阶段分析功能
2006200703midas设计功能介绍新增功能及civil2006功能介绍200703midas分析设计操作界面任意截面消隐显示等6项主要介绍内容主要介绍内容psc设计rc设计及输出计算书功能后处理自定义梁单元内力输出图等5项前处理复制钢束功能等7项midascivilintegratedsolutionsystemcivilstructure2007操作界面操作界面增加了工作面板功能用户可将某类工程建模顺序保存后用于以后类似工程midascivilintegratedsolutionsystemcivilstructure2007表单式图标菜单midascivilintegratedsolutionsystemcivilstructure2007用户定义工作面板命令行输入midascivilintegratedsolutionsystemcivilstructure2007前处理前处理psc桥梁建模助手可以定义截面各部位不同的变化规律自动计算箱形截面有效翼缘宽度非线性弹性支承midascivilintegratedsolutionsystemcivilstructure2007可以在类型模型中共享建模助手信息
Integrated Solution System For Bridge and Civil Structure
甲醇计算
年产40万吨甲醇工艺设计物料衡算:年工作时间8000h一.进塔新鲜气组成计算:1.精馏塔出甲醇量:40*104*103/8000/32.04=1560.549Kmol/h2.设精馏塔损失3%,设计裕度4.5%,则进入精馏塔的粗甲醇中甲醇的含量为:1560.549/(1-4.5%)=1634.083Kmol/h设CO,CO2转化为甲醇的转化率为96%,则进入合成器的新鲜气量为:1634.083/0.96/(0.14+0.13)=6304.333Kmol/h3.则进塔新鲜气组成:CO:6304.333*0.14=882.607Kmol/hCO2:6304.333*0.13=819.563Kmol/hN2: 6304.333*0.01=63.043Kmol/hH2:6304.333*0.69=4343.989Kmol/hCH4:6304.333*0.03=189.129Kmol/h二.出塔物料组成:1. 出塔时粗甲醇中的物料组成:所以: 粗甲醇的摩尔总量: 1634.083/67.416%=2423.88Kmol/h异丁醇的摩尔流量: 2423.88*0.026%=0.63Kmol/h二甲醚的摩尔流量: 2433.88*0.188%=4.557Kmol/h水的摩尔流量: 2433.88*32.37%=784.610Kmol/h 即:2.出塔其他的物料计算:→根据元素守恒: 设 CO 2的摩尔量为A,CO 的摩尔量为B, H 2的摩尔量为C.(1) C 守恒:1634.083+4.557*2+0.63*4+A+B=882.607+819.563…….(M)(2) H守恒:1634.083*4+0.63*10+784.610*2+4.557*6+2C=4343.989*2…….(N)(3) O守恒:1634.083+0.63+784.610+4.557+2A+B=882.607+819.563*2……(F) (4)根据上3式求的: A=41.4Kmol/hB=15.053Kmol/hC=274.392Kmol/h则出塔不凝气体的量:出合成塔的各物料组成:3.有关驰放气的计算:驰放气占气体总量的8%,则排放后剩余92%.所以:剩余的驰放气进入系统循环.三.精馏塔的计算:进精馏塔前粗甲醇中各物料量1.要求精甲醇的纯度为99.98%,则其量:1560.549*0.998=1557.428Kmol/h要求含水量为0.02%,则其量:1560.549*0.0002=0.312Kmol/h2.其余的物料如二甲醚,异丁醇等暂不考虑,其量不变.1、进出合成塔各组分一览表2、进出精馏塔各组分一览表3、有关驰放气各组分一览表。
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第二节 洛必达法则在第一章中,我们曾计算过两个无穷小之比以及两个无穷大之比的未定式的极限. 在那里,计算未定式的极限往往需要经过适当的变形,转化成可利用极限运算法则或重要极限的形式进行计算. 这种变形没有一般方法,需视具体问题而定,属于特定的方法. 本节将用导数作为工具,给出计算未定式极限的一般方法,即洛必达法则. 本节的几个定理所给出的求极限的方法统称为洛必达法则.分布图示⎪⎭⎫ ⎝⎛00 ★ 例1-2 ★ 例3 ★ 例4⎪⎭⎫ ⎝⎛∞∞ ★ 例5★ 例6-7 综合应用 ★ 例8★ 例9★ 例10)0(∞⋅★ 例11)(∞-∞ ★ 例12 ★ 例13★ 例14)0(0★ 例15 ★ 例16 )1(∞★ 例17 ★ 例18★ 例19)(0∞★ 例20★ 例21 ★ 内容小结 ★ 课堂练习 ★ 习题3-2内容要点一、未定式的基本类型:00型与∞∞型;.)()(lim)()(limx F x f x F x f ax ax ''=→→.)()(lim)()(limx F x f x F x f x x ''=∞→∞→二、未定式的其它类型:∞⋅0型,∞-∞型,00,1,0∞∞型 (1)对于∞⋅0型,可将乘积化为除的形式,即化为00或∞∞型的未定式来计算.(2)对于∞-∞型,可利用通分化为0型的未定式来计算.(3) 对于00,1,0∞∞型,可先化以e 为底的指数函数的极限,再利用指数函数的连续性,化为直接求指数的极限,指数的极限为∞⋅0的形式,再化为0或∞∞型的未定式来计算.例题选讲0型例1 (E01) 求 ⋅≠→)0(sin limk xkx x解 原式)()(sin lim''=→x kx x 1cos limkx k x →=.k =例2 (E02) 求 ⋅+--+-→123lim2331x x x x x x解 原式12333lim221---=→x x x x 266lim1-=→x x x .23=注: 上式中, 266lim1-→x x x 已不是未定式,不能再对它应用洛必达法则.例3 (E03) 求.sin 2limx x xe e xxx ----→解 x x xee xx x s i n 2lim----→xe e xxx c o s 12l i m---=-→xee xx x s i n l i m-→-=xee xx x c o s l i m-→+=.2=例4 (E04) 求 xx x 1arctan 2lim-+∞→π.解 xx x 1a r c t a n 2lim-+∞→π22111l i mxxx -+-=+∞→221limxxx +=+∞→1=注: 若求n nn n (1arctan 2lim-+∞→π为自然数)则可利用上面求出的函数极限,得11arctan 2lim=-+∞→nn n π.例5 (E05) 求.ln cot ln limxxx +→解 xxx ln cot ln lim+→xxxx 1)s i n 1(c o t 1lim2-⋅=+→xx x x c o s s i n lim+→-=xxx xx x cos 1limcos sin lim++→→⋅-=.1-=例6 (E06) 求 )0(ln lim>+∞→n xx nx .解 原式11lim-+∞→=n x nxx nx nx1lim+∞→=.0=例7 (E07) 求 ⋅+∞→xnx ex λlim(n 为正整数, 0>λ)解 反复应用洛必达法则n 次,得原式xn x enxλλ1lim-+∞→=xn x exn n λλ22)1(lim-+∞→-= =xn x en λλ!lim+∞→=.0=注:对数函数x ln 、幂函数n x 、指数函数)0(>λλx e 均为当∞→x 时的无穷大,但它们增大的速度很不一样,其增大速度比较: 对数函数<<幂函数<<指数函数.例8 求 .tan tan lim2xx x x x -→解 注意到,~tan x x 则有xx x x x tan tan lim2-→3tan limxx x x -=→2231seclimxx x -=→xxx x 6tan sec2lim2→=xx x x x tan limseclim 3102→→⋅=xx x tan lim310→=.31=注: 洛必达法则虽然是求未定式的一种有效方法, 但若能与其它求极限的方法结合使用, 效果则更好. 例如能化简时应尽可能先化简,可以应用等价无穷小替换或重要极限时,应尽可能应用,以使运算尽可能简捷.例9 (E08) 求 .)21ln()cos 1(3sin 3limx x x x x +--→解 当0→x 时, ,21~cos 12x x -,2~)21ln(x x -故 )21l n ()c o s 1(3s i n 3limx x xx x +--→303s i n 3l i m x x x x -=→2033c o s 33lim xx x -=→x x x 23s i n 3lim 0→=.29=例10 (E09) 求 xxx x sin 1sinlim2→.解 所求极限属于0的未定式.但分子分母分别求导数后,将化为,cos 1cos1sin2limxx xx x -→此式振荡无极限,故洛必达法则失效,不能使用.但原极限是存在的,可用下法求得:xx x x sin 1sin lim2→)1sinsin (lim 0xx xx x ⋅=→xx x x x x sin lim 1sin lim 00→→=.010==例11 (E10) 求 .lim 2x x e x -+∞→ (∞⋅0型)解 对于)0(∞⋅型,可将乘积化为除的形式,即化为0或∞∞型的未定式来计算.xx e x2lim -+∞→2limxe x x +∞→=xexx 2lim+∞→=2limxx e+∞→=.+∞=例12 (E11) 求 )tan (sec lim 2x x x -→π. (∞-∞型)解 对于∞-∞型,可利用通分化为0型的未定式来计算.)tan (sec lim 2x x x -→π)cos sin cos 1(lim 2xx xx -=→πxx x cos sin 1lim2-=→πxx x sin cos lim2--=→π.010==例13 求 )..(1sin 1lim 0∞-∞⎪⎭⎫⎝⎛-→x xx 解 )1sin 1(lim 0xxx -→xx x x x sin sin lim⋅-=→2sin limxx x x -=→xx x 2cos 1lim-=→2sin limx x →=.0=例14 求)].()2[(lim /1∞-∞-+∞→x e x x x解 原式]1)12[(lim 1-+=∞→x x e xx .xe xx x 11)21(lim1-+=∞→直接用洛必达法则,计算量较大.为此作变量替换,令,1xt =则当∞→t 时, ,0→t 所以])2[(lim 1x ex xx -+∞→te t tt 1)21(lim-+=→tt e t 1)12(2lim++=→.3=,1,0∞∞型步骤⎪⎭⎪⎬⎫∞∞0010⇒取对数⎪⎩⎪⎨⎧∞⋅⋅∞⋅ln 01ln 0ln 0⇒.0∞⋅例15 求.lim 0xx x → )0(0解 xx x x x ex ln 0lim lim ++→→=xx x eln lim 0+→=xxx e 1ln lim+→=2011l i m xx x e-+→=0e=.1=例16 (E12) 求 x x x tan 0lim +→. (00型)解 将它变形为xx x x x e x ln tan lim tan 0lim +→=+→由于xx xx x x x x x 2csc1limcot ln limln tan lim +→+→+→==xxx 2sinlim-=+→.01cos sin 2lim=-=+→xx x故.1lim 0tan 0==+→e x x x例17 求)1.(lim 111∞-→xx x解 xx x-→111l i m xxx eln 111lim -→=xx x e-→=1ln lim111l i m 1-→=x x e.1-=e例18 (E13) 求.sin lim cos 110xx x x -→⎪⎭⎫⎝⎛ (∞1型) 解 x x xx co s11)s i n (l i m -→xx xx e s i n lncos 11lim -→=x x x x e c o s1ln sin ln lim--→=由于xx x x cos 1ln sin ln lim--→x x x x sin 1cot lim-=→x x x x x x 20sin sin cos lim -=→30sin cos lim xxx x x -=→23sin limxx x x -=→.31-=所以.31cos 11)sin (lim --→=exx x x例19 求 ().coslim 0xx xπ+→ )1(∞解一 利用洛必达法则.xx x π)(coslim 0+→xxx ecos ln limπ+→=xxx x e21cossin lim⋅-+→=π.2π-=e解二 利用两个重要极限.xx x π)(coslim 0+→xx x π)1cos1(lim 0-+=+→π⋅-⋅-+→-+=xx x x x 1cos1cos 1)1cos1(lim .2π-=e例20 (E14) 求 x x x ln 1)(cot lim +→. (0∞型)解 x x x ln 10)(cot lim +→xx x eln cot ln 0lim +→=xxx e ln cot ln lim+→=xxx x e1csctan lim2⋅-+→=xxx x e sin cos 1lim⋅-+→=.1-=e例21 求().5lim /13xxx xe-+∞→ )(0∞解 xxx x e13)5(l i m -+∞→)5l n (13lim x e x x xe-+∞→=)5l n (1l i m 3x e xxx e-+∞→=因为 )5l n (1lim3x e xxx -+∞→xx e xx )5l n (lim3-=+∞→ )(∞∞1553lim33x eexxx --=+∞→x e e x xx 553lim 33--=+∞→ )(∞∞5333lim33-⋅⋅⋅=+∞→xxx ee xx e3539lim-=+∞→.3=所以 .313)5(lim e x e xx x =-+∞→课堂练习1.设)(x f 有一阶导数,,1)0()0(='=f f 求 .)(ln 1)(sin lim 0x f x f x -→2.设)()(limx g x f 是未定式极限, 如果)()(x g x f ''的极限不存在且不为∞, 是否)()(x g x f 的极限也一定不存在? 举例说明.洛必达(L ’ Hospital ,1661~1704)简介:洛必达(L ’Hospital)是法国数学家,1661年生于巴黎,1704年2月2日卒于巴黎。