Quasi-equilibrium models for triaxially deformed rotating compact stars
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Article A TRP Channel Senses Lysosome Neutralization by Pathogens to Trigger Their ExpulsionGraphical AbstractHighlightsd Intracellular UPEC are encased in exosomes when expelledfrom BECsd UPEC are delivered from autophagosome into MVB,eventually reaching lysosomesd Neutralization of bacteria-bearing lysosomes induceslysosome exocytosisd TRPML3senses neutralized lysosomal pH and triggers Ca2+efflux AuthorsYuxuan Miao,Guojie Li,...,Haoxing Xu, Soman N.AbrahamCorrespondencesoman.abraham@In BriefNon-lytic expulsion of bacteria from infected cells is a powerful cell-autonomous defense strategy to rapidly reduce infection burden in the bladder. The expulsion from infected BECs is triggered by TRPML3.This lysosomal TRP channel senses the UPEC-mediated lysosome neutralization and releasesCa2+,triggering lysosome exocytosis to expel thebacteria. Miao et al.,2015,Cell161,1306–1319June4,2015ª2015Elsevier Inc./10.1016/j.cell.2015.05.009Article A TRP Channel Senses Lysosome Neutralizationby Pathogens to Trigger Their ExpulsionYuxuan Miao,1Guojie Li,2,6Xiaoli Zhang,5Haoxing Xu,5and Soman N.Abraham1,2,3,4,*1Department of Molecular Genetics&Microbiology,Duke University Medical Center,Durham,NC27710,USA2Department of Pathology,Duke University Medical Center,Durham,NC27710,USA3Department of Immunology,Duke University Medical Center,Durham,NC27710,USA4Program in Emerging Infectious Diseases,Duke-National University of Singapore,Singapore169857,Singapore5Department of Molecular,Cellular,and Developmental Biology,University of Michigan,Ann Arbor,MI48109,USA6Present address:Duke Institute for Genome Sciences and Policy,Duke University Medical Center,Durham,NC27710,USA*Correspondence:soman.abraham@/10.1016/j.cell.2015.05.009SUMMARYVertebrate cells have evolved elaborate cell-auto-nomous defense programs to monitor subcellular compartments for infection and to evoke counter-responses.These programs are activated by path-ogen-associated pattern molecules and by various strategies intracellular pathogens employ to alter cellular microenvironments.Here,we show that, when uropathogenic E.coli(UPEC)infect bladder epithelial cells(BECs),they are targeted by autophagy but avoid degradation because of their capacity to neutralize lysosomal pH.This change is detected by mucolipin TRP channel3(TRPML3),a transient receptor potential cation channel localized to lyso-somes.TRPML3activation then spontaneously initi-ates lysosome exocytosis,resulting in expulsion of exosome-encased bacteria.These studies reveal a cellular default system for lysosome homeostasis that has been co-opted by the autonomous defense program to clear recalcitrant pathogens. INTRODUCTIONThe cell-autonomous defense(CAD)program comprises a multi-layered intracellular surveillance system to detect and counter infections.The highly compartmentalized nature of host cells has resulted in the development of various organelle-specific sensors for pathogen-associated molecular patterns(PAMPs), directly noticing molecular signatures of pathogens(Akira et al., 2006).It has recently been proposed that additional sensors exist that detect specific hostile actions of pathogens(also referred to as patterns of pathogenesis),such as penetration of subcellular membrane and disruption of the actin cytoskeleton(Vance et al.,2009).Once these sensors are engaged,the CAD program elicits robust responses to clear the pathogens.A common measure for clearing intracellular pathogens involves detection followed by sequestration of pathogen in an autophagosome,a de-novo-generated membrane-bound compartment,which is promptly shuttled to the lysosome where the pathogens are degraded(Levine et al.,2011).The lysosome is arguably the epicenter of the CAD.Its sterilizing power originates from the concerted actions of numerous factors in the lysosome lumen,such as antimicrobial peptides and proteases,as well as reactive oxygen and nitrogen species,which are highly toxic to the bacteria(Goren,1977).Importantly,the bactericidal actions of these agents are greatly enhanced by the low pH (4.5–5.0)generated inside lysosomes by proton pumping vacuolar (v)-ATPases(Goren,1977).Lysosome function is also exquisitely sensitive to ion homeostasis,and a subfamily of transient receptor potential(TRP)cation channels,referred to as mucolipin TRP channel1-3(TRPML1-3),can be found on the lysosomal membranes,regulating ionflux across lysosomes(Xu and Ren, 2015).In view of the powerful degradative actions of lysosomes, several pathogens have evolved capacities to block the activity of v-ATPases,which markedly attenuates the lysosomes by impairing its acidification(Sturgill-Koszycki et al.,1994).At this time,it is not known whether the CAD program has additional strategies in its arsenal to counter pathogen-mediated subversion of lysosomes.A distinct cellular mechanism for the elimination of invading bacteria involving non-lytic expulsion of intracellular bacteria back to the extracellular milieu was recently described in bladder epithelial cells(BECs)(Bishop et al.,2007).Uropathogenic E.coli (UPEC)circumvent the normally impregnable bladder epithelium by binding avidly to the uroepithelium,triggering focal exocy-tosis of specialized Rab27+fusiform vesicles,which serve as repositories for extra plasma membrane necessary for bladder expansion.When these extruded membranes are subsequently retracted into BECs,adherent UPEC gain entry and slip into Rab27+vesicles(Bishop et al.,2007).Remarkably,the BECs have the innate capacity to expel nearly70%of the infecting bac-teria(Bishop et al.,2007).Much of the underlying mechanisms of how intracellular UPEC are detected and shuttled from their intra-cellular location to the plasma membrane remain a mystery.In this report,we reveal that UPEC expulsion from BECs is initiated in lysosomes and is triggered by a TRP channel upon sensing pathogen-mediated neutralization of lysosomal pH.RESULTSInfected BECs Expel Membrane-Encased UPECImpetus for this study came from the surprisingfinding that a significant portion of UPEC,when freshly isolated from urineof1306Cell161,1306–1319,June4,2015ª2015Elsevier Inc.patients with urinary tract infections (UTIs),were consistently resistant to tobramycin.However,upon subculture,these iso-lates promptly lost their resistance.Given that tobramycin is not membrane permeable (Menashe et al.,2008),we speculated that this transient resistance was attributable to the presence of an encapsulating host membrane.To test this hypothesis,a suspension of bacteria collected from urine of infected mice was treated for 1hr with gentamycin (an antibiotic more routinely used in antibiotic protection assays)with or without 0.1%Triton X-100,which selectively disrupts host membranes.We observed that,in contrast to the gentamicin-alone-treated samples,Triton X-100-treated bacteria were no longer resistant to gentamycin (Figure 1A).We then found at least 10%of the bacteria in urine were stained positive for Caveolin-1,a host membrane marker (Figure 1B).The presence of membrane-encased bacteria in urine of human patients with acute UTIs was similarly observed (Figure 1C),thus validating our notion.To elucidate the underlying basis for this phenomenon,we established an in vitro model of UTIs.The human BEC line 5637was infected by UPEC,and after 8hr of incubation,the extracellular medium was assayed for the presence ofmem-Figure 1.Expelled UPEC Are Encased in Membrane-Bound Vesicles(A)Cell-free urine from infected C57BL/6mice was collected at 6hr post-infection (h.p.i.)and treated with gentamicin with/without 0.1%Triton X-100for 1hr.The surviving colony-forming units (CFU)were quantified.Error bars,SEM;n =9.(B–D)Immunofluorescence staining for Caveolin-1(green)and UPEC (red)in cell-free urine collected from infected mouse at 6hr p.i.(B),UTI patients (C),or culture medium collected from infected BEC line at 8hr p.i.(D).Arrow depicts naked bacteria,and arrowhead depicts vesicle-encased UPEC.The membrane-encased UPEC were quantified and expressed as the percentage of total examined UPEC shown in the parenthesis.Scale bar,5m m.n =3slides.(E)Bacterial viability assay performed on cell-free medium collected from BECs infected with UPEC strain CI5or E.coli K-12strain MG1655at 8hr p.i.and treated with gentamicin or 0.1%Triton X-100alone or gentamicin plus 0.1%Triton X-100for 1hr.Error bars,SEM;n =18.(F)TEM image of extracellular bacteria collected from the culture medium of infected BECs.Arrowhead depicts vesicle-encased bacterium,and arrow depicts a naked bacterium.The membrane-encased ECU were quantified and expressed as the percentage of total examined UPEC shown in the parenthesis.Scale bar,0.2m m.n =3gridsbrane-encased bacteria.Data similar to that found from in vivo studies were ob-tained (Figures 1D and 1E).Interestingly,the presence of membrane-bound bacte-ria was not detectable when using a nonpathogenic E.coli K-12strain to infectthe BECs (Figure 1E).Shown in Figure 1F is a transmission electron microscope image of an extracellular UPEC revealing a distinct membrane around the bacteria.Cumulatively,our in vivo and in vitro data reveal that intracellular UPEC are exported within host-cell-derived vesicles.Expelled UPEC Are Contained within ExosomesBecause several cellular products have been reported to be ex-ported in microvesicles termed exosomes (Simons and Raposo,2009),we explored the possibility that the extracellular UPEC-containing vesicles (EUCVs)were exosomes.Exosomes are typically derived from the inward budding of multivesicular bodies (MVBs)and are of interest because they serve as highlyefficient export vehicles (The´ry et al.,2002).Immunofluorescent staining of EUCVs revealed colocalization of several proteins frequently found in exosomes,including the ESCRT proteins Alix and Tsg101,as well as the tetraspanin CD63(Thery et al.,2006)(Figure 2A).To more quantitatively confirm the presence of exosome markers on EUCVs,the bacteria were first covalentlylinked to magnetic beads before exposure to BECs (Lo¨nnbro et al.,2008),and EUCV-encased bacteria were isolated from cell-free medium on a magnetic rack.We confirmed theCell 161,1306–1319,June 4,2015ª2015Elsevier Inc.1307Figure2.Vesicles Encasing Expelled Bacteria Are Exosomes(A)Immunofluorescence staining of colocalization between exosome markers(green)and extracellular bacteria(red)collected from infected5637BEC line at8hr p.i.The vesicle-encased UPEC were quantified and expressed as the percentage of total examined UPEC shown in the parenthesis.Scale bar,5m m.n=3slides.(B)Immunoblot analysis of lysates of EUCV purified at12hr p.i.from BECs infected with either UPEC,E.coli K12strain,or UPEC with mannose in the medium. Total cell lysates(TCLs)were used to show similar number of cells were treated.(C and D)Bacterial expulsion at6hr p.i.in infected BECs treated with DMSO(vehicle)or15nM dimethyl amiloride(DMA)(C)or transfected with control siRNA or Alix/Tsg101siRNA.Knockdown efficiency is indicated by the western blot alongside.Error bar,SEM;n=18.(E)Bacterial load at24hr p.i.in infected bladder treated with either vehicle(DMSO)or15nM DMA.Error bar,SEM;n=9.(legend continued on next page)1308Cell161,1306–1319,June4,2015ª2015Elsevier Inc.presence of various exosome markers in the EUCV fractions (Figure2B).As controls,we included2%D-mannose in the medium to prevent UPEC adherence and entry(Abraham et al.,1988).We also infected BECs with nonpathogenic E.coli K12MG1655.In both controls,we did not detect any exosome markers associating with extracellular bacteria(Figure2B).As further controls to confirm the rigor of the EUCV purification pro-cedure and to exclude the possibility that EUCV are a result of cell lysis,in the EUCV fraction,we demonstrated the absence of intracellular organelle markers such as GM130,a marker of the Golgi,as well as the absence of Rab27b,a marker for the vacuole in which UPEC initially harbor(Bishop et al.,2007) (Figure2B).We then confirmed involvement of exosomes in bacterial export employing functional assays.To block exosome secre-tion pathway,we either treated UPEC-infected BECs with dimethyl amiloride(DMA),a known inhibitor of exosome release by disrupting calcium signaling(Savina et al.,2003),or knocked down expression of Alix or Tsg101,two key components impli-cated in exosome biogenesis(Baietti et al.,2012).We found that both DMA treatment(Figure2C)and Alix or Tsg101KD(Fig-ure2D)markedly inhibited bacterial expulsion.To evaluate the relevance of exosome-mediated expulsion as a defense mecha-nism against UTI,DMA was transurethrally applied to the blad-ders at2hr post-infection(p.i.).At24hr p.i.,we found that the bacterial load in the DMA-treated mice was markedly more enhanced than controls(Figure2E).Examination of these in-fected bladders revealed that,when the BECs failed to expel bacteria,UPEC accumulated within the uroepithelium,forming large bacterial aggregates(Figure2F).Cumulatively,our data point to exosomes as powerful vehicles for bacterial export following infection.Intracellular UPEC Are Sequestered in MVBs Prior to ExportWe next sought to identify the upstream activities leading to the packaging of UPEC in exosomes.Because exosomes originate from MVBs,we investigated whether UPEC could be found in MVBs.Shown in Figure2G is a representative EM image of a compartment resembling the MVB,which harbors multiple intraluminal vesicles(ILVs)and membrane-bound UPEC.CD63 is a marker of MVBs(Kobayashi et al.,2000),andfluorescent lipid phospholipid N-(Lissamine)rhodamine B sulfonyl dioleoyl-phosphatidylethanolamine(N-Rh-PE)preferentially localizes in MVBs(Vidal et al.,1997).Employing both probes,we verified that some of the intracellular compartments harboring UPEC were doubly positive for CD63and N-Rh-PE(Figure2H).Quan-tification revealed that the percentage of intracellular UPEC found in CD63+vesicles gradually increased,reaching a peak at6hr p.i.(Figure2H).Bacterial Expulsion Involves Autophagy MachineryIn view of the striking reduction in bacterial burden associated with expulsion activity,we hypothesized that this action was initi-ated by the cell-autonomous defense system.To identify the pu-tative intracellular surveillance mechanism involved in expulsion, we analyzed the molecular composition of the purified EUCVs. Interestingly,several components of the autophagy pathway (LC3,Beclin1,and ATG5)were detected in EUCV fractions (Figures3A and S1A).Although autophagy is best known as a cellular homeostasis process,there is also recognition of their involvement in the immune detection of intracellular pathogens (Levine et al.,2011).LC3is a specific membrane marker of the autophagosome that,upon activation,becomes lipidated and converts to LC3II(Kabeya et al.,2000).We detected LC3II in the BEC extract as early as15min after exposure to UPEC(Fig-ure3B).Correspondingly,in the same time frame,we observed intracellular UPEC being captured in the LC3+autophagosomes (Figure3C).Maximum association between autophagosome and UPEC was observed at4hr p.i.(Figure3C).Most of the UPEC that were encased in autophagosomes also colocalized with ubiquitin and P62,markers that tag cargo for sequestration in autophagosomes(Levine et al.,2011)(Figures S1B and S1C). To investigate the involvement of the autophagy machinery in bacterial expulsion,wefirst exposed UPEC-infected BECs to chemical inducers of autophagy.We found that both rapamycin and carbamazepine(CBZ)markedly enhanced bacterial expul-sion(Figure3D).The increased number of extracellular bacteria is not the result of autophagy-induced cell death because neither terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)nor lactate dehydrogenase(LDH)release assays re-vealed any significantly enhanced signs of cell death following rapamycin treatment of infected BECs(Figures S1D and S1E). Conversely,when substrates involved in autophagosome forma-tion,such as ATG5or Beclin1were knocked down,bacterial expulsion was significantly reduced without affecting bacterial entry(Figures3E and S1F).Additionally,we overexpressed ATG4C74A,a dominant-negative mutant that has previously been shown to inhibit autophagosome formation(Fujita et al., 2008).Although there was no difference in the bacterial uptake (Figure S1F),bacterial expulsion was markedly inhibited in these mutant BECs(Figure3F).Because the involvement of autophagy in bacterial expulsion was surprising,we attempted to visualize this process.We un-dertook live-cell imaging of GFP-LC3-expressing BECs infected with RFP-labeled UPEC.In the video(Movie S1)and still images (Figure3G),we observed UPEC encased in LC3-positive vesi-cles trafficking within a BEC before being expelled.Importantly, the autophagosome-encased bacteria rapidly moved toward the cell surface,and following ejection,the expelled bacterium was still encased in the LC3+vesicles.(Movie S1).(F)Immunofluorescence staining of infected bladder treated with either vehicle or DMA for24hr.Collapsed bladder:superficial epithelium(blue),intermediate epithelium(red),UPEC(green).Arrowhead depicts single bacteria,and arrow depicts bacterial aggregates.The bacterial aggregates(>10m m)were quantified. Scale bar:100m m.n=3mice.(G)TEM image shows intracellular UPEC encased in MVBs at4hr p.i.The arrow depicts ILVs encased in MVBs.Bacteria encased in MVBs were quantified and expressed as a percentage of total examined UPEC,shown in the parenthesis.Scale bar,0.2m m.n=3grids(H)Immunofluorescence staining of UPEC(blue)and MVB markers CD63(green)andfluorescent N-Rh-PE(red)at4hr p.i.Scale bar,5m m.The CD63+ compartment-encased UPEC was quantified at2,4,and6hr,expressed as the percentage of total examined UPEC,Scale bar,5m m.n=3slides.Cell161,1306–1319,June4,2015ª2015Elsevier Inc.1309Figure3.Bacterial Expulsion Involves Autophagy Components(A)Immunoblot analysis of autophagy components in EUCVs collected from infected BECs at12hr p.i.(B)Immunoblot of naive BECs(lane1)and infected BECs(lane2)showing increase in LC3II upon UPEC infection for15min.(legend continued on next page)1310Cell161,1306–1319,June4,2015ª2015Elsevier Inc.To further implicate the autophagy pathway in reducing bac-terial burden through bacterial expulsion in BECs,we adminis-tered a peptide,recently shown to trigger autophagy without harmful effects(Shoji-Kawata et al.,2013),into the infected bladder via a pared to the control peptide-treated bladders,the autophagy-inducing peptide markedly reduced bacterial burden of infected bladders(Figure3H).We then sought to specifically knock out Atg3,a key gene involved in autophagosome biogenesis in the superficial epithelial layer of the bladder.To achieve this,mice homologous for the floxed Atg3allele were bred with ER-Cre mice to generate Atg3flox/flox ER-Cre mice,where the Atg3could be inducibly deleted solely in the bladder epithelium by administering4-hy-droxytamoxin(4-OHT)locally in the bladder(see Experimental Procedures).As expected,in the exfoliated superficial epithe-lium extract(see Experimental Procedures),we confirmed that this strategy ensured reproducible knockout of Atg3in the superficial epithelium(Figure3I).Using this animal model, we indeed observed significantly higher bacterial load in the autophagy-deficient bladder epithelium compared to the con-trol(Figure3I).Taken together,our in vitro and in vivo studies reveal the involvement of the autophagy pathway in the expul-sion of bacteria by BECs.Bacterial Neutralization of the Lysosome Triggers ExocytosisBecause the ultimate fate of autophagic cargo is degradation within lysosomes,it was imperative to elucidate why this was replaced by expulsion in UPEC-infected BECs.We verified that autophagosomes still frequently fused with lysosomes in infected BECs(Figure S1G).However,the resulting autolyso-somes failed to become acidified(Figure4A).To test whether this observation was specifically mediated by UPEC,we substituted the UPEC with the relatively innocuous E.coli K-12 strain MG1655,and in this case,bacteria-containing lysosomes were strongly acidified(Figure4A).Intracellular degradation of P62is critically dependent on the pH of lysosomes(Klionsky et al.,2012).We found that,upon in-duction of autophagy in BECs by rapamycin,there was a marked reduction in P62levels(Figure4B).However,UPEC infection,but not E.coli K-12infection,caused dramatic accumulation of P62 in BECs,similar to the effect of bafilomycin A1,a well-known lysosomal v-ATPase inhibitor(Figure4B).It is noteworthy that,when the bafilomycin A1or ammonium chloride was added to E.coli K-12-infected BECs,the number of intracellular bacteria increased compared to vehicle-treated BECs,as these bacteria were no longer killed(Figure4C). When these agents were added to UPEC-infected BECs,no change in intracellular bacterial numbers occurred,presumably because the lysosomes were already neutralized(Figure4C). These observations led us to hypothesize that the neutraliza-tion of the lysosome was a critical signal triggering the expulsion of bacteria-containing exosomes from lysosomes.In earlier experiments,when the E.coli K-12was used to infect BECs, we failed to detect these bacteria in exosomes,as they were usually degraded in the lysosome(Figure1E).However,when we infected BECs with E.coli K-12,followed by bafilomycin A1treatment,we were able to detect significant amounts of extracellular E.coli associated with membranes enriched in CD63and LAMP1(Figure4D).To further test whether neutraliza-tion of lysosomal pH was sufficient to trigger exocytic events from lysosomes,we mimicked the infection condition by inducing autophagy with rapamycin in uninfected BECs for 4hr,followed by bafilomycin A1treatment.We then isolated and examined regular exosomes shed from these cells.Remark-ably,compared to untreated or rapamycin-alone-treated BECs, bafilomycin A1treatment induced a striking increase in the amount of secreted exosomes(Figure4E).Importantly,auto-phagic protein LC3and the lysosomal marker LAMP1were only present in exosomes after bafilomycin A1treatment(Fig-ure4E).Based on these observations,we speculate that bacte-rial expulsion within exosomes is actually mediated by lysosome exocytosis,when the pH of lysosomes is neutralized.A hallmark for lysosome exocytosis is the appearance of lysosomal markers in the plasma membrane.Indeed,fluorescence-acti-vated cell sorting(FACS)analysis of bafilomycin A1-treated BECs,as well as UPEC,but not E.coli K-12-infected BECs, showed striking increases in the cell-surface LAMP1(Figure4F). Probing LAMP1in isolated plasma membrane proteins fractions from BECs(Figure S2A)or assessing lysosomal enzyme activity in the medium of BECs treated with similar conditions also confirmed this pattern of lysosome trafficking(Figure S2B). This movement is restricted to lysosomes,as none of the other organelles markers appeared on the plasma membrane of BECs treated with similar conditions(Figure S2A).Figure4G shows that silencing synaptotagmin7(SYT7),a key mediator of lyso-some exocytosis(Reddy et al.,2001),led to significant abroga-tion of bacterial expulsion,further supporting the notion that bacterial expulsion is mediated by lysosome exocytosis.In sum,these results reveal that lysosome exocytosis resulting in expulsion of UPEC is actually a spontaneous cellular response to alteration of lysosomal conditions.(C)Immunofluorescence staining revealing co-association of autophagosome marker LC3(green)with UPEC(red)in infected BECs at2hr p.i.The number of the LC3-encased UPEC was quantified at2,4,8,and30hr p.i.and expressed as the percentage of total examined UPEC.Scale bar,5m m.n=3slides.(D–F)Bacterial expulsion levels at6hr p.i.in infected BECs treated with(D)DMSO(vehicle),200nm Rapamycin,or30m M CBZ;(E)transfected with control siRNA, ATG5siRNA,or Beclin1siRNA;or(F)transfected with empty vector or plasmid overexpressing ATG4C74A.Knockdown efficiency in(E)is indicated by the western blot alongside.Error bars,SEM(n=18).(G)Still shots from a movie showing intracellular UPEC encapsulation in autophagosomes followed by export.Green,LC3;red,UPEC.For each time point:left, LC3only;right:LC3&UPEC overlay.Dashed lines indicate the cell border assessed from backgroundfluorescence,and the white arrows point to expelled bacteria.(H)Bacterial load at24hr p.i in infected bladder treated with either control or30m g TAT-Beclin peptide.Error bars,SEM;n=9.(I)Bacterial load at24hr p.i.in infected bladder of the WT,4-OHT-treated control Atg3flox/flox,or4-OHT-induced Atg3KO in Atg3flox/flox ER-Cre mice.Western blot probing Atg3in exfoliated superficial epithelium extract shows efficient knockout of Atg3in the superficial epithelial cells of the bladder.Error bars,SEM;n=9.Cell161,1306–1319,June4,2015ª2015Elsevier Inc.1311Figure4.Neutralization of Bacteria-Bearing Lysosomes Triggers Lysosome Exocytosis(A)Immunofluorescence staining of UPEC(blue)or E.coli K-12(blue)-containing lysosomes(green)and lysotracker(red)at6hr p.i.Lysotracker+populations of bacteria-containing lysosomes were quantified and expressed as the percentage of total examined lysosome-enclosed bacteria.Scale bar,5m m.n=3slides.(B)P62level dynamics in naive BECs(lane1)and BECs treated with200nM rapamycin alone(lane2)or rapamycin combined with UPEC(lane3),E.coli K-12(lane4),or1m M bafilomycin A1(lane5).(C)Intracellular bacteria CFU at8hr p.i in BECs infected with either UPEC or E.coli K-12and treated with either vehicle,1m M bafilomycinA1,or50mM NH4Cl. Error bars,SEM;n=18.(D)Immunoblot quantification of CD63or LAMP1present in the EUCV purified from UPEC,E.coli K-12-infected BECs,or E.coli K-12-infected BECs treated with bafilomycin parable CD63or LAMP1in total cell lysate(TCL)suggests that similar numbers of cells were used.(E)Immunoblot quantification of CD63in exosomes purified from naive BECs,BECs treated with200nM rapamycin alone,or BECs treated with200nM rapamycin for4hr,followed by1m M bafilomycinA1treatment parable CD63level in total cell lysate suggests that a similar number of cells were used.(F)FACS analysis of cell-surface LAMP1+populations in naive BECs,BECs treated with rapamycin for4hr followed by bafilomycin A1treatment for12hr,or BECs infected with UPEC CI5or E.coli K-12for12hr.(G)Bacterial expulsion levels at6hr p.i.in infected BECs expressing control shRNA or SYT7shRNA.Knockdown efficiency is indicated by the western blot alongside.Error bars,SEM;n=18.1312Cell161,1306–1319,June4,2015ª2015Elsevier Inc.Sequence of Bacterial Trafficking through Various Subcellular Compartments in BECsSo far,our studies have independently revealed the relevance of exosome formation,autophagy induction,and lysosome exocy-tosis in bacterial expulsion from infected BECs.However,the sequence of these events remains undefined.To better define the trafficking of intracellular UPEC,we undertook a morpho-logical characterization of compartments(see Supplemental Experimental Procedures for identification criteria)housing the intracellular UPEC.At1hr p.i.,which is relatively soon after bac-terial invasion,most intracellular UPEC were contained within a single membrane vacuole(Figure5A,i).This is consistent with earlier reports that UPEC initially reside in fusiform vesicles of BECs(Bishop et al.,2007).However,after further incubation ( 2hr p.i.),UPEC started to partially or completely escape into the cytosol,as they did not appear to be completely encapsu-lated by a membrane(Figure5A,ii).At the same time point, some bacteria could also be found within autophagosomes, which are defined by their tightlyfitting double-layered mem-branes(Figure5A,iii).At4hr p.i.,intracellular UPEC were observed within MVBs,which we defined as single membrane compartments that house membrane-bound bacteria,as well as ILVs(Figure5A,iv).Next,we demonstrated that autophagosome encapsulation precedes deposition of bacteria in ILVs within MVBs.When autophagy was enhanced,the number of exosome-encased UPEC increased correspondingly(Figures5B and5C),whereas this number was significantly reduced in ATG5or Beclin1KD BECs(Figures5B and5C).Additionally,when we examined Alix or Tsg101KD BECs,we failed to detect rapamycin-enhanced expulsion in these cells(Figure5D).We also observed that LC3colocalizes with CD63+compartments that house UPEC(Figure5E),and when autophagy was abrogated,bacte-rial localization in CD63+compartments was markedly reduced (Figure5F).We further sought to investigate whether the lysosome is the site where bacterial expulsion occurred.We genetically blocked each key stage of the proposed trafficking pathway by selectively knocking down functionally relevant components,such as auto-phagosome formation(ATG5KD),autophagosome and MVB fusion(VAMP3KD)(Figure S2C)(Fader et al.,2009),MVB and lysosome fusion(Rab7KD)(Figure S2C)(Vanlandingham and Cer-esa,2009),and lysosome exocytosis(SYT7KD)or simultaneously deficient in two of these processes.If parallel routes exist for bac-terial export,then the impact of blocking traffic at an early stage (e.g.,at autophagosome formation)or simultaneously inhibiting two of these processes will predictably have a larger inhibitory impact on exocytosis than any single blockage at the later stages, (e.g.,lysosome exocytosis).However,we found that the inhibition with each of the KD was highly significant and,importantly,com-parable(Figure5G).Furthermore,examination of the extracellular UPEC revealed that no detectable exosome associated with UPEC in SYT7KD or Rab7KD BECs(Figure5H).The abovefindings confirm that the exosome-encased UPEC are exclusively being exported from the lysosomes.This is sur-prising,as under physiologic conditions,exosomes are routinely released from MVBs(The´ry et al.,2002).We hypothesized that, upon induction of autophagy,MVBs follow a distinct trafficking rout preferentially targeting their contents into lysosomes.We found that,if we only induced autophagy in BECs,the expected exosome release is dramatically abrogated(Figure4E).Addition-ally,although rapamycin plus bafilomycin A1treatment led to a large-scale release of exosomes(Figure4E),this induced-exo-some release was drastically reduced in Rab7KD BECs where the fusion between MVBs and lysosomes was impaired,indi-cating that the exosomes released from lysosomes originated from MVBs(Figure S2D).To confirm this notion,we examined exosome release in SYT7KD BECs.In these cells,only lysosome exocytosis is affected,but not MVB.We observed that,whereas the induced large-scale exosome release was markedly impaired in the SYT7KD cells(Figure S2E),the normal MVB-mediated exosomes secretion under physiological conditions was unaffected(Figure S2E).Cumulatively,our data support the model that UPEC are transported sequentially through multiple intracellular compartments,but they are not expelled from BECs until they reach the lysosomes and only when the lysosomal pH is neutralized by UPEC.TRPML3Initiates Bacterial Expulsion from Lysosomes Next,we sought to identify the critical lysosomal sensor capable of detecting pH changes and regulating bacterial expulsion from infected BECs.Because calcium is essential for most exocytic events(Jahn and Su¨dhof,1999),we pretreated BECs with BAPTA-AM,an intracellular calcium chelator,and found that BAPTA-AM,but not BAPTA(which cannot penetrate BECs), significantly suppressed bacterial expulsion(Figure6A),indi-cating that an intracellular calcium store was important for initi-ating bacterial expulsion.Several recent studies have revealed that the lysosome is actually a key calcium store,and multiple calcium channels,including a subfamily of TRP cation channel known as mucolipin TRP channels(TRPML1-3),are located on lysosomes to regulate calcium efflux upon stimulation(Xu and Ren,2015).Based on this knowledge,we decided to examine the involvement of any specific TRPMLs.Wefirst tested the effect of SN2,a recently described agonist for the TRPMLs(Grimm et al.,2010),and found it drastically increased bacterial expulsion(Figure6B)without accompanying cell lysis (Figure S3A).On the other hand,the ML-SI1(Samie et al., 2013),an antagonist of the TRPMLs,markedly blocked bacterial expulsion(Figure6C).To examine which of these TRPMLs is important for bacterial expulsion,we constructed BECs stably expressing shRNA targeting each of TRPMLs,and we found that TRPML3KD was most effective in abolishing bacterial expulsion activity,even in SN2-treated BECs(Figures6D and 6B).In addition,we are able to detect CD63associated with extracellular bacteria emanating from control but not from TRPML3KD BECs,which further verified that TRPML3is involved in the expulsion of exosome-encased UPEC(Fig-ure6E).TRPML3is localized on the lysosome,including the ones encapsulating UPEC(Figure6F).Interestingly,bacterial clearance is deficient in TRPML3KD BECs,which failed to expel intralysosomal UPEC,resulting in marked increase of the intracellular bacterial load(Figure6G).Consistent with this observation,in the TRPML3KD BECs,many bacteria in the lysosome appeared to have multiplied,forming large intracel-lular aggregates(Figure6H).Cell161,1306–1319,June4,2015ª2015Elsevier Inc.1313。
腺癌的疗效和安全性分析[J].国际肿瘤学杂志,2022,49(11):671-676.[18]李原.白蛋白紫杉醇对比多西他噻治疗对晚期乳腺癌患者生存质量的影响[J].中国药物与临床,2021,21(23):3880-3883.[19] YONESHIMA Y,MORITA S,ANDO M,et al. Phase 3trial comparing Nanoparticle Albumin-bound Paclitaxel with Docetaxel for previously treated advanced NSCLC[J]. J ThoracOncol,2021,16(9):1523-1532.[20]罗艳,敖秋玲,谢文亮,等.白蛋白结合型紫杉醇联合表柔比星治疗复发转移性乳腺癌患者的效果[J].中国民康医学,2021,33(23):26-27,30.[21]师文聪,邓智平.白蛋白结合型紫杉醇联合表柔比星及环磷酰胺在乳腺癌新辅助化疗中的效果及安全性[J].肿瘤研究与临床,2021,33(3):200-203.(收稿日期:2023-04-07) (本文编辑:程旭然)①江苏省第二中医院 江苏 南京 210000益肾泄浊汤加减治疗肾虚湿浊证尿毒症的效果孙凡舒① 李立① 杨亚丽① 赵亮①【摘要】 目的:探讨益肾泄浊汤加减治疗肾虚湿浊证尿毒症的效果。
方法:选取2020年1月—2022年12月江苏省第二中医院收治的102例肾虚湿浊证尿毒症患者。
根据随机数表法将其分为对照组和观察组,各51例。
两组均给予常规治疗,观察组给予益肾泄浊汤加减治疗。
比较两组临床疗效,治疗前及治疗4周后营养指标、肾功能指标、中医症状积分及不良反应。
结果:观察组总有效率高于对照组,差异有统计学意义(P <0.05)。
治疗4周后,观察组转铁蛋白(TRF)、血红蛋白(Hb)、前白蛋白(PA)水平均高于对照组,差异有统计学意义(P <0.05)。
Designation:D5084–03Standard Test Methods forMeasurement of Hydraulic Conductivity of Saturated PorousMaterials Using a Flexible Wall Permeameter1This standard is issued under thefixed designation D5084;the number immediately following the designation indicates the year oforiginal adoption or,in the case of revision,the year of last revision.A number in parentheses indicates the year of last reapproval.Asuperscript epsilon(e)indicates an editorial change since the last revision or reapproval.1.Scope*1.1These test methods cover laboratory measurement of thehydraulic conductivity(also referred to as coeffıcient of per-meability)of water-saturated porous materials with aflexiblewall permeameter at temperatures between about15and30°C(59and86°F).Temperatures outside this range may be used;however,the user would have to determine the specific gravityof mercury and R T(see10.3)at those temperatures using datafrom Handbook of Chemistry and Physics.There are sixalternate methods or hydraulic systems that may be used tomeasure the hydraulic conductivity.These hydraulic systemsare as follows:1.1.1Method A—Constant Head1.1.2Method B—Falling Head,constant tailwater elevation1.1.3Method C—Falling Head,rising tailwater elevation1.1.4Method D—Constant Rate of Flow1.1.5Method E—Constant V olume–Constant Head(bymercury)1.1.6Method F—Constant V olume–Falling Head(by mer-cury),rising tailwater elevation1.2These test methods use water as the permeant liquid;see4.3and Section6on Reagents for water requirements.1.3These test methods may be utilized on all specimentypes(undisturbed,reconstituted,remolded,compacted,etc.)that have a hydraulic conductivity less than about1310−6m/s(1310−4cm/s),providing the head loss requirements of5.2.3are met.For the constant-volume methods,the hydraulicconductivity typically has to be less than about1310−7m/s.1.3.1If the hydraulic conductivity is greater than about1310−6m/s,but not more than about1310−5m/s;then thesize of the hydraulic tubing needs to be increased along withthe porosity of the porous end pieces.Other strategies,such asusing higher viscosityfluid or properly decreasing the cross-sectional area of the test specimen,or both,may also bepossible.The key criterion is that the requirements covered inSection5have to be met.1.3.2If the hydraulic conductivity is less than about1310−11m/s,then standard hydraulic systems and tempera-ture environments will typically not suffice.Strategies that maybe possible when dealing with such impervious materials mayinclude the following:(a)controlling the temperature moreprecisely,(b)adoption of unsteady state measurements byusing high-accuracy equipment along with the rigorous analy-ses for determining the hydraulic parameters(this approachreduces testing duration according to Zhang et al.(1)2),and(c)shortening the length or enlarging the cross-sectional area,orboth,of the test specimen.Other items,such as use of higherhydraulic gradients,lower viscosityfluid,elimination of anypossible chemical gradients and bacterial growth,and strictverification of leakage,may also be considered.1.4The hydraulic conductivity of materials with hydraulicconductivities greater than1310−5m/s may be determined byTest Method D2434.1.5All observed and calculated values shall conform to theguide for significant digits and rounding established in PracticeD6026.1.5.1The procedures used to specify how data are collected,recorded,and calculated in this standard are regarded as theindustry standard.In addition,they are representative of thesignificant digits that should generally be retained.The proce-dures used do not consider material variation,purpose forobtaining the data,special purpose studies,or any consider-ations for the user’s objectives;and it is common practice toincrease or reduce significant digits of reported data to becommensurate with these considerations.It is beyond the scopeof this standard to consider significant digits used in analysismethods for engineering design.1.6This standard also contains a Hazards section aboutusing mercury,see Section7.1.7The time to perform this test depends on such items asthe Method(A,B,C,D,E,or F)used,the initial degree ofsaturation of the test specimen and the hydraulic conductivityof the test specimen.The constant volume Methods(E and F)and Method D require the shortest period-of-time.Typically atest can be performed using Methods D,E,or F within two to 1This standard is under the jurisdiction of ASTM Committee D18on Soil andRock and is the direct responsibility of Subcommittee D18.04on HydrologicProperties of Soil and Rocks.Current edition approved Nov.1,2003.Published January2004.Originallyapproved st previous edition approved in2000as D5084–00e1.2The boldface numbers in parentheses refer to the list of references appended tothis standard.*A Summary of Changes section appears at the end of this standard.Copyright©ASTM International,100Barr Harbor Drive,PO Box C700,West Conshohocken,PA19428-2959,United States.three days.Methods A,B,and C take a longer period-of-time,from a few days to a few weeks depending on the hydraulic conductivity.Typically,about one week is required for hydrau-lic conductivities on the order of 1310–9m/s.The testing time is ultimately controlled by meeting the equilibrium criteria for each Method (see 9.5).1.8The values stated in SI units are to be regarded as the standard,unless other units are specifically given.By tradition in U.S.practice,hydraulic conductivity is reported in centime-ters per second,although the common SI units for hydraulic conductivity is meters per second.1.9This standard does not purport to address all of the safety concerns,if any,associated with its use.It is the responsibility of the user of this standard to establish appro-priate safety and health practices and determine the applica-bility of regulatory limitations prior to use.2.Referenced Documents 2.1ASTM Standards:3D 653Terminology Relating to Soil,Rock,and Contained FluidsD 698Test Methods for Laboratory Compaction Character-istics of Soil Using Standard Effort (12,4000ft-lbf/ft 3(600kN-m/m 3))D 854Test Method for Specific Gravity of Soil Solids by Water PycnometerD 1557Test Methods for Laboratory Compaction Charac-teristics of Soil Using Modified Effort (56,000ft-lbf/ft 3(2,700kN-m/m 3))D 1587Practice for Thin-Walled Tube Geotechnical Sam-pling of SoilsD 2113Practice for Rock Core Drilling and Sampling for Site InvestigationD 2216Test Method for Laboratory Determination of Water (Moisture)Content of Soil and Rock by MassD 2434Test Method for Permeability of Granular Soils (Constant Head)D 2435Test Method for One-Dimensional Consolidation Properties of SoilD 3550Practice for Ring-Lined Barrel Sampling of Soils D 3740Practice for Minimum Requirements for Agencies Engaged in the Testing and/or Inspection of Soil and Rock Used in Engineering Design and ConstructionD 4220Practices for Preserving and Transporting Soil SamplesD 4753Specification for Evaluating,Selecting and Speci-fying Balances and Scales for Use in Soil,Rock,and Construction Materials TestingD 4767Test Method for Consolidated Undrained Triaxial Compression Test for Cohesive SoilsD 5079Practices for Preserving and Transporting Rock Core SamplesD 6026Practice for Using Significant Digits in Geotechni-cal DataD 6151Practice for Using Hollow-Stem Augers for Geo-technical Exploration and Soil SamplingD 6169Guide for Selection of Soil and Rock Sampling Devices Used with Drill Rigs for Environmental Investi-gations 3.Terminology3.1Definitions:3.1.1For common definitions of other terms in this stan-dard,see Terminology D 653.3.1.2head loss,h L or h —the change in total head of water across a given distance.3.1.2.1Discussion —In hydraulic conductivity testing,typi-cally the change in total head is across the influent and effluent lines connected to the permeameter,while the given distance is typically the length of the test specimen.3.1.3permeameter —the apparatus (cell)containing the test specimen in a hydraulic conductivity test.3.1.3.1Discussion —The apparatus in this case is typically a triaxial-type cell with all of its components (top and bottom specimen caps,stones,and filter paper;membrane;chamber;top and bottom plates;valves;etc.).3.1.4hydraulic conductivity,k —the rate of discharge of water under laminar flow conditions through a unit cross-sectional area of porous medium under a unit hydraulic gradient and standard temperature conditions (20°C).3.1.4.1Discussion —In hydraulic conductivity testing,the term coeffıcient of permeability is often used instead of hydraulic conductivity ,but hydraulic conductivity is used exclusively in this standard.A more complete discussion of the terminology associated with Darcy’s law is given in the literature.(2,3)3.1.5pore volume of flow —in hydraulic conductivity test-ing ,the cumulative quantity of flow into a test specimen divided by the volume of voids in the specimen.4.Significance and Use4.1These test methods apply to one-dimensional,laminar flow of water within porous materials such as soil and rock.4.2The hydraulic conductivity of porous materials gener-ally decreases with an increasing amount of air in the pores of the material.These test methods apply to water-saturated porous materials containing virtually no air.4.3These test methods apply to permeation of porous materials with water.Permeation with other liquids,such as chemical wastes,can be accomplished using procedures simi-lar to those described in these test methods.However,these test methods are only intended to be used when water is the permeant liquid.See Section 6.4.4Darcy’s law is assumed to be valid and the hydraulic conductivity is essentially unaffected by hydraulic gradient.4.5These test methods provide a means for determining hydraulic conductivity at a controlled level of effective stress.Hydraulic conductivity varies with varying void ratio,which changes when the effective stress changes.If the void ratio is changed,the hydraulic conductivity of the test specimen will likely change,see Appendix X2.To determine the relationship3For referenced ASTM standards,visit the ASTM website,,or contact ASTM Customer Service at service@.For Annual Book of ASTM Standards volume information,refer to the standard’s Document Summary page on the ASTMwebsite.between hydraulic conductivity and void ratio,the hydraulic conductivity test would have to be repeated at different effective stresses.4.6The correlation between results obtained using these test methods and the hydraulic conductivities of in-placefield materials has not been fully investigated.Experience has sometimes shown that hydraulic conductivities measured on small test specimens are not necessarily the same as larger-scale values.Therefore,the results should be applied tofield situations with caution and by qualified personnel.4.7In most cases,when testing high swell potential mate-rials and using a constant-volume hydraulic system,the effec-tive confining stress should be about 1.5times the swell pressure of the test specimen or a stress which prevents swelling.If the confining stress is less than the swell pressure, anomalousflow conditions my occur;e.g.,mercury column(s) move in the wrong direction.N OTE1—The quality of the result produced by this standard is dependent of the competence of the personnel performing it and the suitability of the equipment and facilities used.Agencies that meet the criteria of Practice D3740are generally considered capable of competent and objective testing,sampling,inspection,ers of this standard are cautioned that compliance with Practice D3740does not in itself assure reliable results.Reliable results depend on many factors;Practice D3740 provides a means of evaluating some of those factors.5.Apparatus5.1Hydraulic System—Constant head(Method A),falling head(Methods B and C),constant rate offlow(Method D), constant volume-constant head(Method E),or constant volume-falling head(Method F)systems may be utilized provided they meet the following criteria:5.1.1Constant Head—The system must be capable of maintaining constant hydraulic pressures to65%or better and shall include means to measure the hydraulic pressures to within the prescribed tolerance.In addition,the head loss across the permeameter must be held constant to65%or better and shall be measured with the same accuracy or better.A pressure gage,electronic pressure transducer,or any other device of suitable accuracy shall measure pressures to a minimum of three significant digits.The last digit may be due to estimation,see5.1.1.1.5.1.1.1Practice D6026discusses the use or application of estimated digits.When the last digit is estimated and that reading is a function of the eye’s elevation/location,then a mirror or another device is required to reduce the reading error caused by parallax.5.1.2Falling Head—The system shall allow for measure-ment of the applied head loss,thus hydraulic gradient,to65% or better at any time.In addition,the ratio of initial head loss divided byfinal head loss over an interval of time shall be measured such that this computed ratio is accurate to65%or better.The head loss shall be measured with a pressure gage, electronic pressure transducer,engineer’s scale,graduated pipette,or any other device of suitable accuracy to a minimum of three significant digits.The last digit may be due to estimation,see5.1.1.1.Falling head tests may be performed with either a constant tailwater elevation(Method B)or a rising tailwater elevation(Method C),see Fig.1.This schematic of a hydraulic system presents the basic components needed to meet the objectives of Method C.Other hydraulic systems or schematics that meet these objectives are acceptable.5.1.3Constant Rate of Flow—The system must be capable of maintaining a constant rate offlow through the specimen to 65%or better.Flow measurement shall be by calibrated syringe,graduated pipette,or other device of suitable accuracy. The head loss across the permeameter shall be measured to a minimum of three significant digits and to an accuracy of 65%or better using an electronic pressure transducer(s)or other device(s)of suitable accuracy.The last digit may be due to estimation,see5.1.1.1.More information on testing with a constant rate offlow is given in the literature(4).5.1.4Constant Volume-Constant Head(CVCH)—The sys-tem,with mercury to create the head loss,must be capable of maintaining a constant head loss cross the permeameter to 65%or better and shall allow for measurement of the applied head loss to65%or better at any time.The head loss shall be measured to a minimum of three significant digits with an electronic pressure transducer(s)or equivalent device,(5)or based upon the pressure head caused by the mercury column, see10.1.2.The last digit may be due to estimation,see5.1.1.1.5.1.4.1Schematics of two CVCH systems are shown in Fig. 2and Fig.3.In each of these systems,the mercury-filled portion of the tubing may be continuous for constant head loss to be maintained.For the system showed in Fig.2,the head loss remains constant provided the mercury column is vertical and is retained in only one half of the burette system(left burette in Fig.2).In the system shown in Fig.3,the head loss remains constant provided the water-mercury interface on the effluent end remains in the upper horizontal tube,and the water-mercury interface on the influent end remains in the lower horizontal tube.These schematics present the basic components needed to meet the objectives of Method E.Other hydraulic systems or schematics that meet these objectives are acceptable.5.1.4.2These types of hydraulic systems are typically not used to study the temporal or pore-fluid effect on hydraulic conductivity.The total volume of the specimen is maintained constant using this procedure,thereby significantly reducing effects caused by seepage stresses,porefluid interactions,etc. Rather,these systems are intended for determining the hydrau-lic conductivity of a material as rapidly as possible.5.1.4.3Hazards—Since this hydraulic system contains mer-cury,special health and safety precautions have to be consid-ered.See Section7.5.1.4.4Caution—For these types of hydraulic systems to function properly,the separation of the mercury column has to be prevented.To prevent separation,the mercury and“constant head”tube have to remain relatively clean,and the inside diameter of this tube cannot be too large;typically a capillary tube is used.The larger diameterflushing tube(Fig.2)is added to enableflushing clean water through the system without excessive mercury displacement.Traps to prevent the acciden-talflow of mercury out of the“Constant Head”tube orflushing tube are not shown in Fig.2and Fig.3.5.1.5Constant Volume-Falling Head(CVFH)—The system, with mercury to create the head loss,shall meet thecriteriagiven in 5.1.2.The head loss shall be measured to a minimum of three significant digits with an electronic pressure transduc-er(s)or equivalent device(s),(5)or based upon the differential elevation between the top surfaces of the mercury level in the headwater and tailwater tubes.The last digit may be due to estimation,see 5.1.1.1.5.1.5.1A schematic drawing of a typical CVFH hydraulic system is shown in Fig.4(5).Typically,the tailwater tube has a smaller area than the headwater tube to increase the sensi-tivity of flow measurements,and to enable flushing clean water through the system without excessive mercury displacement in the headwater tube.The schematic of the hydraulic system in Fig.4presents the basic components needed to meet the objectives of Method F.Other hydraulic systems or schematics that meet these objectives are acceptable.The development of the hydraulic conductivity equation for this type of system is given in Appendix X1.5.1.5.2See 5.1.4.2.5.1.5.3Hazards —Since this hydraulic system contains mer-cury,special health and safety precautions have to be consid-ered.See Section 7.5.1.5.4Caution —For these types of hydraulic systems to function properly,the separation of the mercury column and entrapment of water within the mercury column have to be prevented.To prevent such problems,the mercury and tubes have to remain relatively clean.In addition,if different size headwater and tailwater tubes are used,capillary head might have to be accounted for,see Appendix X1,X1.2.3.2,and X1.4.Traps to prevent the accidental flow of mercury out of the tubes are not shown in Fig.4.5.1.6System De-airing —The hydraulic system shall be designed to facilitate rapid and complete removal of free air bubbles from flow lines;e.g.,using properly sized tubing and ball valves and fittings without pipe threads.Properly sized tubing,etc.,means they are small enough to prevent entrap-ment of air bubbles,but not so small that the requirements of 5.2.3cannot be met.5.1.7Back Pressure System —The hydraulic system shall have the capability to apply back pressure to the specimen to facilitate saturation.The system shall be capable of maintain-ing the applied back pressure throughout the duration of hydraulic conductivity measurements.The back pressure sys-tem shall be capable of applying,controlling,and measuring the back pressure to 65%or better of the applied pressure.The back pressure may be provided by a compressed gas supply,a deadweight acting on a piston,or any other method capable of applying and controlling the back pressure to the tolerance prescribed in thisparagraph.FIG.1Falling Head –Rising Tail System,MethodCN OTE 2—Application of gas pressure directly to a fluid will dissolve gas in the fluid.A variety of techniques are available to minimize dissolution of gas in the back pressure fluid,including separation of gas and liquid phases with a bladder and frequent replacement of the liquid with de-aired water.5.2Flow Measurement System —Both inflow and outflow volumes shall be measured unless the lack of leakage,conti-nuity of flow,and cessation of consolidation or swelling can be verified by other means.Flow volumes shall be measured by a graduated accumulator,graduated pipette,vertical standpipe in conjunction with an electronic pressure transducer,or other volume-measuring device of suitable accuracy.5.2.1Flow Accuracy —Required accuracy for the quantity of flow measured over an interval of time is 65%or better.5.2.2De-airing and Compliance of the System —The flow-measurement system shall contain a minimum of dead space and be capable of complete and rapid pliance of the system in response to changes in pressure shall be minimized by using a stiff flow measurement system.Rigid tubing,such as metallic or rigid thermoplastic tubing,or glass shall be used.5.2.3Head Losses —Head losses in the tubes,valves,po-rous end pieces,and filter paper may lead to error.To guard against such errors,the permeameter shall be assembled with no specimen inside and then the hydraulic system filled.5.2.3.1Constant or Falling Head —If a constant or falling head test is to be used,the hydraulic pressures or heads that will be used in testing a specimen shall be applied,and the rate of flow measured with an accuracy of 65%or better.This rate of flow shall be at least ten times greater than the rate of flow that is measured when a specimen is placed inside the permeameter and the same hydraulic pressures or heads are applied.5.2.3.2Constant Rate of Flow —If a constant rate of flow test is to be used,the rate of flow to be used in testing a specimen shall be supplied to the permeameter and the head loss measured.The head loss without a specimen shall be less than 0.1times the head loss when a specimen is present.5.3Permeameter Cell Pressure System —The system for pressurizing the permeameter cell shall be capable of applying and controlling the cell pressure to 65%or better oftheFIG.2Constant Volume –Constant Head System,Method E(5)applied pressure.However,the effective stress on the test specimen (which is the difference between the cell pressure and the pore water pressure)shall be maintained to the desired value with an accuracy of 610%or better.The device for pressurizing the cell may consist of a reservoir connected to the permeameter cell and partially filled with de-aired water,with the upper part of the reservoir connected to a compressed gas supply or other source of pressure (see Note 3).The gas pressure shall be controlled by a pressure regulator and measured by a pressure gage,electronic pressure transducer,or any other device capable of measuring to the prescribed tolerance.A hydraulic system pressurized by deadweight acting on a piston or any other pressure device capable of applying and controlling the permeameter cell pressure within the tolerance prescribed in this paragraph may be used.N OTE 3—De-aired water is commonly used for the cell fluid to minimize potential for diffusion of air through the membrane into the specimen.Other fluids that have low gas solubilities such as oils,are also acceptable,provided they do not react with components of the permeame-ter.Also,use of a long (approximately 5to 7m)tube connecting the pressurized cell liquid to the cell helps to delay the appearance of air in the cell fluid and to reduce the flow of dissolved air into the cell.5.4Permeameter Cell —An apparatus shall be provided in which the specimen and porous end pieces,enclosed by a membrane sealed to the cap and base,are subjected to controlled fluid pressures.A schematic diagram of a typical permeameter cell and falling head (raising tailwater)hydraulic system is shown in Fig.1.5.4.1The permeameter cell may allow for observation of changes in height of the specimen,either by observation through the cell wall using a cathetometer or other instrument,or by monitoring of either a loading piston or an extensometer extending through the top plate of the cell bearing on the top cap and attached to a dial indicator or other measuring device.The piston or extensometer should pass through a bushing and seal incorporated into the top plate and shall be loaded with sufficient force to compensate for the cell pressure acting over the cross-sectional area of the piston where it passes through the seal.If deformations are measured,the deformation indi-cator shall be a dial indicator or cathetometer graduated to 0.5mm or 0.01in.or better and having an adequate travel range.Any other measuring device meeting these requirements is acceptable.5.4.2In order to facilitate gas removal,and thus saturation of the hydraulic system,four drainage lines leading to the specimen,two each to the base and top cap,are recommended.The drainage lines shall be controlled by no-volume-change valves,such as ball valves,and shall be designed to minimize dead space in the lines.5.4.3Top Cap and Base —An impermeable,rigid top cap and base shall be used to support the specimen and provide for transmission of permeant liquid to and from the specimen.The diameter or width of the top cap and base shall be equal to the diameter or width of the specimen to 65%or better.The base shall prevent leakage,lateral motion,or tilting,and the topcapFIG.3Constant Volume—Constant Head System,MethodEshall be designed to receive the piston or extensometer,if used,such that the piston-to-top cap contact area is concentric with the cap.The surface of the base and top cap that contacts the membrane to form a seal shall be smooth and free of scratches.5.4.4Flexible Membranes —The flexible membrane used to encase the specimen shall provide reliable protection against leakage.The membrane shall be carefully inspected prior to use.If any flaws or pinholes are evident,the membrane shall be discarded.To minimize restraint to the specimen,the diameter or width of the non-stretched membrane shall be between 90and 95%of that of the specimen.The membrane shall be sealed to the specimen base and cap with rubber O-rings for which the unstressed,inside diameter or width is less than 90%of the diameter or width of the base and cap,or by any other method that will produce an adequate seal.N OTE 4—Membranes may be tested for flaws by placing them around a form sealed at both ends with rubber O-rings,subjecting them to a small air pressure on the inside,and then dipping them into water.If air bubbles come up from any point on the membrane,or if any visible flaws are observed,the membrane shall be discarded.5.4.5Porous End Pieces —The porous end pieces shall be of silicon carbide,aluminum oxide,or other material that is not attacked by the specimen or permeant liquid.The end pieces shall have plane and smooth surfaces and be free of cracks,chips,and discontinuities.They shall be checked regularly to ensure that they are not clogged.5.4.5.1The porous end pieces shall be the same diameter or width (65%or better)as the specimen,and the thickness shall be sufficient to prevent breaking.5.4.5.2The hydraulic conductivity of the porous end pieces shall be significantly greater than that of the specimen to be tested.The requirements outlined in 5.2.3ensure this criterion is met.5.4.6Filter Paper —If necessary to prevent intrusion of material into the pores of the porous end pieces,one or more sheets of filter paper shall be placed between the top and bottom porous end pieces and the specimen.The paper shall have a negligibly small hydraulic impedance.The require-ments outlined in 5.2.3ensure that the impedance is small.5.5Equipment for Compacting a Specimen —Equipment (including compactor and mold)suitable for the method of compaction specified by the requester shall be used.5.6Sample Extruder —When the material being tested is a soil core,the soil core shall usually be removed from the sampler with an extruder.The sample extruder shall be capable of extruding the soil core from the sampling tube in the same direction of travel in which the sample entered the tube and with minimum disturbance of the sample.If the soil core is not extruded vertically,care should be taken to avoid bending stresses on the core due to gravity.Conditions at the time of sample extrusion may dictate the direction of removal,but the principal concern is to keep the degree of disturbanceminimal.FIG.4Constant Volume –Falling Head System,Method F(5)。
In 1887, the German physicist Erwin Schrödinger proposed a radial solution to the Maxwell-Schrödinger equation. This equation describes the behavior of an electron in an atom and is used to calculate its energy levels. The radial solution was found to be valid for all values of angular momentum quantum number l, which means that it can describe any type of atomic orbital.The existence and multiplicity of this radial solution has been studied extensively since then. It has been shown that there are infinitely many solutions for each value of l, with each one corresponding to a different energy level. Furthermore, these solutions can be divided into two categories: bound states and scattering states. Bound states have negative energies and correspond to electrons that are trapped within the atom; scattering states have positive energies and correspond to electrons that escape from the atom after being excited by external radiation or collisions with other particles.The existence and multiplicity of these solutions is important because they provide insight into how atoms interact with their environment through electromagnetic radiation or collisions with other particles. They also help us understand why certain elements form molecules when combined together, as well as why some elements remain stable while others decay over time due to radioactive processes such as alpha decay or beta decay.。
专利名称:Quasi-asynchronous sampling method andsystem发明人:Randall, Bruce E.申请号:EP83401854.1申请日:19830923公开号:EP0104998A2公开日:19840404专利内容由知识产权出版社提供专利附图:摘要:K samples of L successive cycles of an electrical signal that is at leastapproximately periodic are taken, where K = LN + D, to cause corresponding samples of successive cycles to unidirectionally drift. The value of N defines the number of samples per waveform cycle, the value of D is related to drift sampling rate. Unidirectionalsampling drift ensures that all points on the signal wave form over a number of cycles are sampled to avoid missing a periodic waveform characteristic that might tend to occur between samples. Since the sampling rate is synchronized to L cycles of the input signal,the number of samples per cycle of the input signal is substantially constant as a function of input signal frequency. Quasi-asynchronous sampling in accordance with the invention is particularly useful for making electrical power line measurements in environmentswhere power line frequency tends to vary.申请人:SANGAMO WESTON, INC.地址:180 Technology Drive Norcross Georgia 30092 US 国籍:US代理机构:Chareyron, Lucien更多信息请下载全文后查看。
土木工程专业英语生词整理声明:本文档是笔者结合清华大学俞家欢老师《土木工程专业英语》与同济大学苏小卒老师《土木工程专业英语》上下册整理的一些土木工程领域常用的生词,仅供有需要的朋友学习交流使用。
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barrages 水库canals 运河distributary 引流工程highway 公路expressway 高速公路(美式)levee 码头mitigate floods 减轻洪水construction 建造→施工survey 调查→工程勘察helipad 停机坪truck terminal 铁路站台sewage treatment 污水处理demolish 拆毁central government or local administration中央或地方政府reinvestment 再投资petroleum revenue 石油财政(指迪拜)resort island 度假岛desert country 沙漠地区国家waterfront 滨海区residential apartment 公寓住宅gulf 海湾buttressed design 扶壁设计tripod foundation 三脚架式基础tide and current 潮起潮落traffic congestion 交通拥挤regulate 限制financial crisis 金融危机escalate rent cost 租金持续上涨mega-project 大项目revale 媲美microcosm 缩影tropical cyclone 热带气旋(台风)downstream 产业链下游desalination 海水淡化distillation 蒸馏ubiquitous 无处不在的marine species 海洋生物density 重度(类似密度)gravity 重力→比重toughness 韧性ductility 延性brittleness 脆性creep 徐变,蠕变stiffness 刚度impact strength 冲击强度thermal 热力学特性corrosion resistance 耐腐蚀性acidity 酸性,酸度alkalinity 碱性,碱度sound 声absorption 吸收transmission 传导reflection 反射acoustical 声学特性optical 光学特性physiochemical 生化特性abrasion 磨损indentation 缺口,凹痕machining 蚀刻scratch 切削oxidize 氧化cement-mortar 水泥砂浆quarry 采掘lintel 过梁ballast 压载材料(铁轨下的垫材)brick 砖refractory brick 耐火砖ventilator 通风设备railway coaches 铁路车厢wagon 马车sleeper 枕木masonry construction 砌体结构gravel 砂石,砾石property 性能plastic stage 塑性workability 和易性mix 混合→拌和place 放置→浇筑compacte 压实finish 竣工homogeneity 同质性segregation 离析性coarse aggregate 粗骨料water tightness 水密性bleeding 裂隙pore 孔隙porous 多孔的harshness 粗糙的poorly graded aggregate 骨料级配不良withstand 抵抗moisture variation 潮湿变化freeze and thaw 冻融impermeability 密闭性resistance to wear and tear 耐磨性reinforced cement concrete 钢筋混凝土prestressed cement concrete 预应力混凝土silo 筒仓bunker 煤仓,地堡,掩体ornamental structure 装饰性结构tensile load 抗拉强度slab 板tall chimney 高烟囱aqueduct 高架渠ferro-cement 钢纤维混凝土skeletal steel 钢骨架pre-cast unit 预制单元(构件)vault 拱顶shell 壳结构grid surface 网格表面folded plate 褶皱板partition 隔断ductile 延展性好的susceptible to damage 易损坏harmony express 和谐号动车asbestos cement sheet 石棉水泥板shape memory alloy 形状记忆合金magnetostrictioe material 磁致伸缩材料piezoelectric material 压电材料electrorheological fluid 电流变材料viscosity 黏性deflection 挠度vibration 振动noise mitigation 噪声抑制bridge deck 桥面bridge pier 桥墩slab 板beam 梁grider 大梁、桁架restrained structure 超静定结构differential settlement 不均匀沉降hydrostatic load 静水荷载earth load 土压力earthquake load 地震荷载tile 瓦felt and gravel 毡及卵石层gypsum block 石膏wood stud 木栓texture of the building surface建筑表面形状纹理stiffness of the structure 建筑结构刚度stagnation pressure 风压wind suction 风吸力leeward 背风面的coefficient 系数gust factor 阵风系数essential factor 重要性系数hazardous facility 危险设备seismic load 地震荷载vibration 振型whiplash effect 鞭梢效应a portion of the base shear force底部剪力法storey 楼层hydraulic 水运elevator shaft 电梯井筒folded plate 折板屋顶bearing wall 承重墙shear wall 剪力墙unobstructed surface 无障碍表面erect 建造,建立residential 民用建筑institutional 公共结构serviceability 实用性failure 极限状态rehabilitation 加固verification 验证load transfer mechanism 荷载传递机理flexure 弯曲,屈曲torsion 扭转shear 剪切membrane 拱grid 柱reinforcement bars(rebars)钢筋patent 专利precast concrete 预制混凝土cast concrete 现浇混凝土brick chip 碎砖块cement hydrates 水泥水化物microscopic opaque crystal 微小透明晶体microscopic rigid lattice 微观晶格corrugated 有螺纹的cohesion 黏结力passivate 钝化(钢筋)chloride 氯离子provision 规定,要求moisture 潮湿,水分humidity 湿度,湿热curvature 弯曲,曲度,曲率singly-reinforced beam 单筋梁under-reinforced beam 少筋梁over-reinforced beam 超筋梁balanced-reinforced beam 适筋梁instantaneous 立即,突然material-safety factor 安全系数allowable stress design 许用应力设计flake 剥落mix design 配合比设计penetrate 侵入serviceability failure in limit state design正常使用极限状态破坏bond failure 黏结失效carbonation 碳化作用neutralisation 中和作用(即碳化作用)optimal 最佳选择phenolphthalein indicator 酚酞指示剂admixtures 外加剂rapid set-up 快速初凝mitigate 减轻,缓和capillary 毛细管sound attenuating layer 隔音层slump 坍落度concrete vibrating 振捣steel sire 箍筋iron chain suspension bridge 铁链吊桥rivets connection 铆钉连接wrought iron technology 锻铁技术cast iron 铸铁high-strength bolt 高强度螺栓fabrication 制作technical code 技术规程cold-formed thin-wall steel 冷弯薄壁型钢masonry 砌体材料plasticity 塑性tenacity 韧性isotropic 各项异性ideal elastic-plastic 理想弹塑体proportional limit 比例极限(σp)yield strength 屈服强度tensile strength 抗拉强度fabrication 制作weldability 焊接性能air tightness 气密性press vessel 压力容器heat resistance 耐热性non-refractory 防火性能差fire proof protection 防火保护brittle fracture 脆性断裂large span structure 大跨度结构crane 吊车profiled steel sheet 异型钢板mega-frame structure 组合结构demountable structure 可拆卸结构steel scaffolding 钢脚桁架rupture 破裂buckling 搭扣,屈曲formation of mechanism 形成机构(塑性铰)wind induced oscillation 风致振动provision 规定load-carrying structure 承重结构percentage of elongation 伸长率cold-bending test 冷弯实验single story frame 单层结构bridge crane 桥式起重机residual stress 残余应力sun-dried mud 晒干的泥土shale 页岩lateral load 水平荷载seismic 地震raw material 原材料mortar 砂浆mica 云母filthy 有机杂质odor 气体iron compound 铁化合物mold 模具stirrup 箍筋gravel 砾石compact sand 紧密的砂土trench 沟槽over footing 地梁adherence 黏结性confining column 构造柱minimum covering for concrete最小保护层厚度water cement ratio 水灰比mid-rise segment 中高层建筑glulam beam 胶合木梁dwelling 住宅sport arene 运动场better seismic performance更好的抗震性能interior 内部gypsum 石膏板external cladding 外覆盖层fire-rated assembly 防火组件hybrid construction 混合结构practical 实用的exterior infill wall 外部填充墙energy performance 节能性能renovation 装修flat roof 平屋面extra accommodation 阁楼solid wood panel 实木板freight 运送到up-front invesrment 前期投资mortise 榫眼,榫接tenon 榫erected 直立的flammable 易燃物purlin 檩条spatial construction 空间结构high load-bearing capacity很高的荷载承担能力compaction 密实erection 建造hollow steel tube 中空钢管unfilled tube 中空钢管confinement 约束作用schematic view 示意图favorable stress distribution有利的荷载分布terrain 地形cantilever bridge 悬臂桥arch bridge 拱桥suspension bridge 悬索桥cable-stayed bridge 斜拉桥truss bridge 桁架桥pier 桥墩dissipation 消散(荷载)box girder 箱梁meticulous analysis 精细分析foot bridge 人行桥false work 脚手架counter balance 平衡抵消anchor arm 锚固臂outermost 最外侧pinned joint 铰接节点segment construction 分布施工canyon 峡谷abutment 桥墩(基台)viaduct 高架桥thrust 推力spandrel 拱尖catenary 锁链aforementioned 如前所述的bluff 悬崖pillar 塔架slender 细的parabola 抛物线lattice girder 格构梁drought 干旱flood 洪水cyclone 飓风environmental degradation 环境恶化meteological disaster 气象灾害casualty 伤亡invariably 始终如一的secondary disaster 次生灾害earthquake portent 地震预警landslide 滑坡collapse 崩塌debris flow 泥石流river erosion 河流侵蚀turbid 浑浊fissure 裂缝resilient 弹回,有弹力的sewerage 污水,排水设备snowmelt 融雪水escalation of cast 超过预算time overrun 工期延长pharmaceutical 制药mitigate potential risk 化解潜在风险tenet 宗旨aqueduct 高架渠,渡槽ballistic 弹道学causeway 长堤,堤道channel 沟渠,海峡,槽钢equilibrium 平衡(状态)excavation 挖掘hydraulic 水力的mason 砖瓦石匠obelisk 方尖石塔quarry 采石场sewage 污水reimbursable 可报销的,可补偿的aerated concrete 加气混凝土aggregate 骨料binding agent 粘合剂bitumen 沥青blunt 钝的bolt 螺栓cast 浇筑clamp 夹子corrode 腐蚀course (砖)层,行form 模板grout 薄砂浆,灰浆multistory building 多层建筑rate of contraction 收缩率rate of expansion 膨胀率rivet 铆钉,铆接screw 螺丝钉slab 平板spray 喷射tarlike 沥青thread 螺纹tile 瓦片versatile 多用途的weld 焊接blastfurnace 高炉矿渣asbestos 石棉瓦modulus of rupture 断裂模量hydration 水化作用cohesive 粘性的rapid-hardening 速凝grading 级配dampness 湿度,含水量accelerator 速凝剂inhibitor 抑制剂plasticizer 塑化剂grouting agent 灌浆剂consistency 稠度mobility 流动性compactability 可密实性biaxial 二轴的distortion 扭曲,变形elongate 拉长,延长moment 力矩prismatic 棱柱形的superposition 迭加作用transverse 横向的triaxial 三轴的,空间的vessel 容器bracing 拉条,撑杆conservation of energy 能量守恒conveyor 输送机deviation 偏差flexibility coefficient 柔度系数method of section 截面法pin connection 铰接principle of virtual work 虚功原理redundant force 冗余力sever 断开,分开support reaction 支反力truss 桁架unit-load method 单位荷载法corridor 走廊counteration 退化ductile failure 延性破坏erection 直立建筑物impact factor 冲击系数iterative 重复的,反复的layout 规划,设计图案maintainability 可维护性monorail 单轨铁路quasi-permanent 准永久的sustained 持续不变的tenant 承租人torque 扭矩torsional 扭力,扭转的buggy 手推运料车commentary 注释,条文规范contractor 承包商couple 力偶entrain 加气(给混凝土)fire rating 耐火等级oscillate 摆动,震动rigidity 刚度shoring 支撑anchorage 锚固centroid 形心concrete cover 混凝土保护层eccentricity 偏心距helix 螺旋线的incipient 刚出现的lap splice 搭接longitudinal 纵向的pitch 坡度spall 剥落symmetrical 对称的tie 绑扎(钢筋)curvature 曲率detrimental 有害的flange 翼缘web 腹板render 粉刷,抹灰foundry 铸造厂incombustible 防火的residual 残余的stocky 短粗的vitreous 玻璃的withstand 抵抗,承受gusset 节点板,角板imperfection 缺陷purlin 檩条rafter 椽子slenderness 长细比spandrel 拱肩,托梁stringer 桁条,纵梁sway 晃动,侧接移forge 锻造inspection 检查,弹伤shank 末梢wrench 扳手nut 螺母slag 钢渣coordinate 坐标cruise 勘察datum 基准面elevation 高程,海拔remote sensing 遥感conductivity 传导性gradient 梯度ballast 石渣boulder 漂石cobble 卵石cohesive 有粘聚力的consolidation 固结depression 降低fine 细粒grit 粗砂silt 淤泥immediate settlement 瞬时沉降consolidation settlement 固结沉降pore water 孔隙水back-acting shovel 反铲(挖掘机的)bearing capacity 承载力bore hole 钻孔boring 钻探coefficient of permeability 渗透系数proposed structure 拟建结构shear vane test 十字板剪切试验consistency 稠度attorney 代理人currency 流通货币dispatch 派遣elicit 引出procure 获得remuneration 报酬stipulate 规定surety 担保tendering 招标,投标withhold 保留bidder 投标人contemplate 注视letting 公开开标recourse 追索stock holder 股东performance bond 履约profit margin 利润率stem from 基于a letter of intent 意向书rule of thumb 经验方法radius of gyration 回转半径transverse load 横向荷载shop-fabricated 工厂预制的capping beam 压顶梁channel element 槽型构件cladding brickwork 维护砌体cornice 檐口,飞檐finish 饰面,粉刷flat slab 无梁板footing 基础,垫层head room 净空高度joist 托梁,肋maritime 靠海的,港口的two-way slab 双向板waffle slab 密肋板yield line 塑性铰线inflate 充气,使膨胀perturbation 摄动,扰动cavity wall 空心墙chicken-wire 铁丝织网cut-and-try 试验性的emulsion 乳胶head(end) joint 端灰缝high-lift 高扬程的mortar bed 砂浆平缝partition 分隔墙mortar joint 灰缝retarder 缓凝剂rubble 毛石,块石veneer 饰面,镶板retaining wall 挡土墙custom-designed 定制cut-and-fill 挖方和填方placement 浇捣concrete batching plant 混凝土搅拌站bentonite slurry 泥浆asphalt 沥青,柏油gutter 排水沟auger boring 螺纹钻探group pile-efficiency 群桩效应in-situ 现场的,原位的fracture 断裂hysteresis 滞回inter-storey drift 层间位移longitudinal reinforcement 纵筋monotonic loading 单调加载partial safety factor 分项系数secondary-order effects 二阶效应shear span 剪跨sidesway 侧倾,侧移。
Discrete Applied Mathematics157(2009)2217–2220Contents lists available at ScienceDirectDiscrete Applied Mathematicsjournal homepage:/locate/damPreface$This special issue on Networks in Computational Biology is based on a workshop at Middle East Technical University in Ankara,Turkey,September10–12,2006(.tr/Networks_in_Computational_Biology/). Computational biology is one of the many currently emerging areas of applied mathematics and science.During the last century,cooperation between biology and chemistry,physics,mathematics,and other sciences increased dramatically,thus providing a solid foundation for,and initiating an enormous momentum in,many areas of the life sciences.This special issue focuses on networks,a topic that is equally important in biology and mathematics,and presents snapshots of current theoretical and methodological work in network analysis.Both discrete and continuous optimization,dynamical systems, graph theory,pertinent inverse problems,and data mining procedures are addressed.The principal goal of this special issue is to contribute to the mathematical foundation of computational biology by stressing its particular aspects relating to network theory.This special issue consists of25articles,written by65authors and rigorously reviewed by70referees.The guest editors express their cordial thanks to all of them,as well as to the Editors-in-Chief of Discrete Applied Mathematics,Prof.Dr.Endre Boros and his predecessor,Prof.Dr.Peter L.Hammer,who was one of the initiators of this special issue but left us in2006, and to Mrs.Katie D’Agosta who was at our side in each phase of preparation of this DAM special issue.The articles are ordered according to their contents.Let us briefly summarize them:In the paper of Jacek Błażewicz,Dorota Formanowicz,Piotr Formanowicz,Andrea Sackmann,and MichałSajkowski, entitled Modeling the process of human body iron homeostasis using a variant of timed Petri nets,the standard model of body iron homeostasis is enriched by including the durations of the pertinent biochemical reactions.A Petri-net variant in which, at each node,a time interval is specified is used in order to describe the time lag of the commencement of conditions that must be fulfilled before a biochemical reaction can start.Due to critical changes in the environment,switches can occur in metabolic networks that lead to systems exhibiting simultaneously discrete and continuous dynamics.Hybrid systems represent this accurately.The paper Modeling and simulation of metabolic networks for estimation of biomass-accumulation parameters by Uˇg ur Kaplan,Metin Türkay,Bülent Karasözen,and Lorenz Biegler develops a hybrid system to simulate cell-metabolism dynamics that includes the effects of extra-cellular stresses on metabolic responses.Path-finding approaches to metabolic-pathway analysis adopt a graph-theoretical approach to determine the reactions that an organism might use to transform a source compound into a target compound.In the contribution Path-finding approaches and metabolic pathways,Francisco J.Planes and John E.Beasley examine the effectiveness of using compound-node connectivities in a path-finding approach.An approach to path finding based on integer programming is also presented. Existing literature is reviewed.This paper is well illustrated and provides many examples as well as,as an extra service,some supplementary information.In A new constraint-based description of the steady-state flux cone of metabolic networks,Abdelhalim Larhlimi and Alexander Bockmayr present a new constraint-based approach to metabolic-pathway analysis.Based on sets of non-negativity constraints,it uses a description of the set of all possible flux distributions over a metabolic network at a steady state in terms of the steady-state flux cone.The constraints can be identified with irreversible reactions and,thus,allow a direct interpretation.The resulting description of the flux cone is minimal and unique.Furthermore,it satisfies a simplicity condition similar to the one for elementary flux modes.Most biological networks share some properties like being,e.g.,‘‘scale free’’.Etienne Birmeléproposes a new random-graph model in his contribution A scale-free graph model based on bipartite graphs that can be interpreted in terms of metabolic networks,and exhibits this specific feature.$Dedicated to our dear teacher and friend Prof.Dr.Peter Ladislaw Hammer(1936–2006).0166-218X/$–see front matter©2009Elsevier B.V.All rights reserved.doi:10.1016/j.dam.2009.01.0212218Preface/Discrete Applied Mathematics157(2009)2217–2220Differential equations have been established to quantitatively model the dynamic behaviour of regulatory networks representing interactions between cell components.In the paper Inference of an oscillating model for the yeast cell cycle, Nicole Radde and Lars Kaderali study differential equations within a Bayesian setting.First,an oscillating core network is learned that is to be extended,in a second step,using‘‘Bayesian’’methodology.A specifically designed hierarchical prior distribution over interaction strengths prevents overfitting and drives the solutions to sparse networks.An application to a real-world data set is provided,and its dynamical behaviour is reconstructed.The contribution An introduction to the perplex number system by Jerry L.R.Chandler derives from his approach to theoretical chemistry,and provides a universal source of diagrams.The perplex number system,a new logic for describing relationships between concrete objects and processes,provides in particular an exact notation for chemistry without invoking either chemical or‘‘alchemical’’symbols.Practical applications to concrete compounds(e.g.,isomers of ethanol and dimethyl ether)are given.In conjunction with the real number system,the relations between perplex numbers and scientific theories of concrete systems(e.g.,intermolecular dynamics,molecular biology,and individual medicine)are described.Since exact determination of haplotype blocks is usually impossible,a method is desired which can account for recombinations,especially,via phylogenetic networks or a simplified version.In their work Haplotype inferring via galled-tree networks using a hypergraph-covering problem for special genotype matrices,Arvind Gupta,Ján Maňuch,Ladislav Stacho, and Xiaohong Zhao reduce the problem via galled-tree networks to a hypergraph-covering problem for genotype matrices satisfying a certain combinatorial condition.Experiments on real data show that this condition is mostly satisfied when the minor alleles(per SNP)reach at least30%.Recently the Quartet-Net or,for short,‘‘QNet’’method was introduced by Stefan Grünewald et al.as a method for computing phylogenetic split networks from a collection of weighted quartet trees.Here,Stefan Grünewald,Vincent Moulton,and Andreas Spillner show that QNet is a‘‘consistent’’method.This key property of QNet does not only guarantee to produce a tree if the input corresponds to a tree—and an outer-labeled planar split network if the input corresponds to such a network;the proof given in their contribution Consistency of the QNet algorithm for generating planar split networks from weighted quartets also provides the main guiding principle for the design of the method.Kangal and Akbash dogs are the two well-known shepherd dog breeds in Turkey.In the article The genetic relationship between Kangal,Akbash,and other dog populations,Evren Koban,Çigdem Gökçek Saraç,Sinan Can Açan,Peter Savolainen, andİnci Togan present a comparative examination by mitochondrial DNA control region,using a consensus neighbour-joining tree with bootstrapping which is constructed from pairwise FST values between populations.This study indicates that Kangal and Akbash dogs belong to different branches of the tree,i.e.,they might have descended maternally from rather different origins created by an early branching event in the history of the domestic dogs of Eurasia.In their paper The Asian contribution to the Turkish population with respect to the Balkans:Y-chromosome perspective,Ceren Caner Berkman and inci Togan investigate historical migrations from Asia using computational approaches.The admixture method of Chikhi et al.was used to estimate the male genetic contribution of Central Asia to hybrids.The authors observed that the male contribution from Central Asia to the Turkish population with reference to the Balkans was13%.Comparison of the admixture estimate for Turkey with those of neighboring populations indicated that the Central Asian contribution was lowest in Turkey.Split-decomposition theory deals with relations between real-valued split systems and metrics.In his work Split decomposition over an Abelian group Part2:Group-valued split systems with weakly compatible support,Andreas Dress uses a general conceptual framework to study these relations from an essentially algebraic point of view.He establishes the principal results of split-decomposition theory regarding split systems with weakly compatible support within this new algebraic framework.This study contributes to computational biology by analyzing the conceptual mathematical foundations of a tool widely used in phylogenetic analysis and studies of bio-diversity.The contribution Phylogenetic graph models beyond trees of Ulrik Brandes and Sabine Cornelsen deals with methods for phylogenetic analysis,i.e.,the study of kinship relationships between species.The authors demonstrate that the phylogenetic tree model can be generalized to a cactus(i.e.,a tree all of whose2-connected components are cycles)without losing computational efficiency.A cactus can represent a quadratic rather than a linear number of splits in linear space.They show how to decide in linear time whether a set of splits can be accommodated by a cactus model and,in that case,how to construct it within the same time bounds.Finally,the authors briefly discuss further generalizations of tree models.In their paper Whole-genome prokaryotic clustering based on gene lengths,Alexander Bolshoy and Zeev Volkovich present a novel method of taxonomic analysis constructed on the basis of gene content and lengths of orthologous genes of 66completely sequenced genomes of unicellular organisms.They cluster given input data using an application of the information-bottleneck method for unsupervised clustering.This approach is not a regular distance-based method and, thus,differs from other recently published whole-genome-based clustering techniques.The results correlate well with the standard‘‘tree of life’’.For characterization of prokaryotic genomes we used clustering methods based on mean DNA curvature distributions in coding and noncoding regions.In their article Prokaryote clustering based on DNA curvature distributions,due to the extensive amount of data Limor Kozobay-Avraham,Sergey Hosida,Zeev Volkovich,and Alexander Bolshoy were able to define the external and internal factors influencing the curvature distribution in promoter and terminator regions.Prokaryotes grow in the wide temperature range from4◦C to100◦C.Each type of bacteria has an optimal temperature for growth.They found very strong correlation between arrangements of prokaryotes according to the growth temperature and clustering based on curvature excess in promoter and terminator regions.They found also that the main internal factors influencingPreface/Discrete Applied Mathematics157(2009)2217–22202219 the curvature excess are genome size and A+T composition.Two clustering methods,K-means and PAM,were applied and produced very similar clusterings that reflect the aforementioned genomic attributes and environmental conditions of the species’habitat.The paper Pattern analysis for the prediction of fungal pro-peptide cleavage sites by SüreyyaÖzöˇgür Ayzüz,John Shawe-Taylor,Gerhard-Wilhelm Weber,and Zümrüt B.Ögel applies support-vector machines to predict the pro-peptide cleavage site of fungal extra-cellular proteins displaying mostly a monobasic or dibasic processing site.A specific kernel is expressed as an application of the Gaussian kernel via feature spaces.The novel approach simultaneously performs model selection, tests the accuracy,and computes confidence levels.The results are found to be accurate and compared with the ones provided by a server.Preetam Ghosh,Samik Ghosh,Kalyan Basu,and Sajal Das adopt an‘‘in silico’’stochastic-event-based simulation methodology to determine the temporal dynamics of different molecules.In their paper Parametric modeling of protein–DNA binding kinetics:A discrete event-based simulation approach,they present a parametric model for predicting the execution time of protein–DNA binding.It considers the actual binding mechanism along with some approximated protein-and DNA-structural information using a collision-theory-based approach incorporating important biological parameters and functions into the consideration.Murat Ali Bayır,Tacettin Doˇg acan Güney,and Tolga Can propose a novel technique in their paper Integration of topological measures for eliminating non-specific interactions in protein interaction networks for removing non-specific interactions in a large-scale protein–protein interaction network.After transforming the interaction network into a line graph,they compute betweenness and other clustering coefficients for all the edges in the network.The authors use confidence estimates and validate their method by comparing the results of a test case relating to the detection of a molecular complex with reality.The article Graph spectra as a systematic tool in computational biology by Anirban Banarjee and Jürgen Jost deals with the obviously important question of how biological content can be extracted from the graphs to which biological data are often reduced.From the spectrum of the graph’s Laplacian that yields an essentially complete qualitative characterization of a graph,a spectral density plot is derived that can easily be represented graphically and,therefore,analyzed visually and compared for different classes of networks.The authors apply this method to the study of protein–protein interaction and other biological and infrastructural networks.It is detected that specific such classes of networks exhibit common features in their spectral plots that readily distinguish them from other classes.This represents a valuable complement to the currently fashionable search for universal properties that hold across networks emanating from many different contexts.Konstantin Klemm and Peter F.Stadler’s Note on fundamental,nonfundamental,and robust cycle bases investigates the mutual relationships between various classes of cycle bases in a network that have been studied in the literature.The authors show for instance that strictly fundamental bases are not necessarily cyclically robust;and that,conversely, cyclically robust bases are not necessarily fundamental.The contribution focuses on cyclically robust cycle bases whose existence for arbitrary graphs remains open despite their practical use for generating all cycles of a given2-connected graph. It presents also a class of cubic graphs for which cyclically robust bases can be constructed explicitly.Understanding the interplay and function of a system’s components also requires the study of the system’s functional response to controlled experimental perturbations.For biological systems,it is problematic with an experimental design to aim at a complete identification of the system’s mechanisms.In his contribution A refinement of the common-cause principle,Nihat Ay employs graph theory and studies the interplay between stochastic dependence and causal relations within Bayesian networks and information theory.Applying a causal information-flow measure,he provides a quantitative refinement of Reichenbach’s common-cause principle.Based on observing an appropriate collection of nodes of the network, this refinement allows one to infer a hitherto unknown lower bound for information flows within the network.In their article Discovering cis-regulatory modules by optimizing barbecues,Axel Mosig,Türker Bıyıkoˇg lu,Sonja J.Prohaska, and Peter F.Stadler ask for simultaneously stabbing a maximum number of differently coloured intervals from K arrangements of coloured intervals.A decision version of this best barbecue problem is shown to be NP-complete.Because of the relevance for complex regulatory networks on gene expression in eukaryotic cells,they propose algorithmic variations that are suitable for the analysis of real data sets comprising either many sequences or many binding sites.The optimization problem studied generalizes frequent itemset mining.The contribution A mathematical program to refine gene regulatory networks by Guglielmo Lulli and Martin Romauch proposes a methodology for making sense of large,multiple time-series data sets arising in expression analysis.It introduces a mathematical model for producing a reduced and coherent regulatory system,provided a putative regulatory network is given.Two equivalent formulations of the problem are given,and NP-completeness is established.For solving large-scale instances,the authors implemented an ant-colony optimization procedure.The proposed algorithm is validated by a computational analysis on randomly generated test instances.The practicability of the proposed methodology is also shown using real data for Saccharomyces cerevisiae.Jutta Gebert,Nicole Radde,Ulrich Faigle,Julia Strösser,and Andreas Burkovski aim in their paper Modelling and simulation of nitrogen regulation in Corynebacterium glutamicum at understanding and predicting the interactions of macromolecules inside the cell.It sets up a theoretical model for biochemical networks,and introduces a general method for parameter estimation,applicable in the case of very short time series.This approach is applied to a special system concerning nitrogen uptake.The equations are set up for its main components,the corresponding optimization problem is formulated and solved, and simulations are carried out.2220Preface/Discrete Applied Mathematics157(2009)2217–2220Gerhard-Wilhelm Weber,Ömür Uˇg ur,Pakize Taylan,and Aysun Tezel model and predict gene-expression patterns incorporating a rigorous treatment of environmental aspects,and aspects of errors and uncertainty.For this purpose,they employ Chebyshev approximation and generalized semi-infinite optimization in their paper On optimization,dynamics and uncertainty:A tutorial for gene–environment networks.Then,time-discretized dynamical systems are studied,the region of parametric stability is detected by a combinatorial algorithm and,then,the topological landscape of gene–environment networks is analyzed in terms of its‘‘structural stability’’.We are convinced that all papers selected for this special issue constitute valuable contributions to many different areas in computational biology,employing methods from discrete mathematics and related fields.We again thank all colleagues who have participated in this exciting endeavor with care,foresight,and vision,for their highly appreciated help.Guest editorsAndreas DressBülent KarasözenPeter F.StadlerGerhard-Wilhelm Weber125July2008Available online29March2009 1Assistant to the guest editors:Mrs.Cand.MSc.Bengisen Pekmen(Institute of Applied Mathematics,METU,Ankara).。
SWISS-MODEL 蛋白质结构预测SWISS-MODEL是一项预测蛋白质三级结构的服务,它利用同源建模的方法实现对一段未知序列的三级结构的预测。
该服务创建于1993年,开创了自动建模的先河,并且它是讫今为止应用最广泛的免费服务之一。
同源建模法预测蛋白质三级结构一般由四步完成:1.从待测蛋白质序列出发,搜索蛋白质结构数据库(如PDB,SWISS-PROT等),得到许多相似序列(同源序列),选定其中一个(或几个)作为待测蛋白质序列的模板;2.待测蛋白质序列与选定的模板进行再次比对,插入各种可能的空位使两者的保守位置尽量对齐;3.建模:调整待测蛋白序列中主链各个原子的位置,产生与模板相同或相似的空间结构——待测蛋白质空间结构模型;4.利用能量最小化原理,使待测蛋白质侧链基团处于能量最小的位置。
最后提供给用户的是经过如上四步(或重复其中某几步)后得到的蛋白质三级结构。
SWISS-MODEL工作模式SWISS-MODEL服务器是以用户输入信息的最小化为目的设计的,即在最简单的情况下,用户仅提供一条目标蛋白的氨基酸序列。
由于比较建模程序可以具有不同的复杂性,用户输入一些额外信息对建模程序的运行有时是有必要的,比如,选择不同的模板或者调整目标模板序列比对。
该服务主要有以下三种方式:?First Approach mode(简捷模式):这种模式提供一个简捷的用户介面:用户只需要输入一条氨基酸序列,服务器就会自动选择合适的模板。
或者,用户也可以自己指定模板(最多5条),这些模板可以来自ExPDB模板数据库(也可以是用户选择的含坐标参数的模板文件)。
如果一条模板与提交的目标序列相似度大于25%,建模程序就会自动开始运行。
但是,模板的可靠性会随着模板与目标序列之间的相似度的降低而降低,如果相似度不到50%往往就需要用手工来调整序列比对。
这种模式只能进行大于25个残基的单链蛋白三维结构预测。
?Alignment Interface(比对界面):这种模式要求用户提供两条已经比对好的序列,并指定哪一条是目标序列,哪一条是模板序列(模板序列应该对应于ExPDB模板数据库中一条已经知道其空间结构的蛋白序列)。
第16卷第1期精密成形工程2024年1月JOURNAL OF NETSHAPE FORMING ENGINEERING33基于机器学习的钛合金弹性模量预测方法研究王园园,武川*,彭志伟,时文才(天津职业技术师范大学汽车模具智能制造技术国家地方联合工程实验室,天津 300222)摘要:目的探索一种高效可行的预测方法以提高钛合金弹性模量的预测精度,采用第一性原理计算方法与机器学习相结合的方式建立高精度的预测模型。
方法通过数据挖掘获取材料数据库中钛合金的力学性质微观结构参数,结合第一性原理计算方法构建初始数据集,并对其进行预处理,包括噪音消除、归一化及标准化,以得到高质量的数据集。
同时,采用随机森林特征重要性分析法对输入参数进行筛选,去除弱相关变量以降低预测模型的复杂度。
在此基础上,构建随机森林模型、支持向量机模型、BP神经网络模型及优化后的GA-BP神经网络模型,综合对比各模型的回归能力,分析误差后选出最优的算法模型。
结果最终建立了钛合金弹性模量预测模型,其中随机森林模型、支持向量机模型、BP神经网络模型、GA-BP神经网络模型的预测相关系数R分别为0.836、0.943、0.917、0.986。
结论 GA-BP模型对弹性模量的预测误差基本保持在5%~7%。
遗传算法可以优化BP神经网络的权值和阈值,使预测精度大幅提升。
说明通过该方法可以实现钛合金弹性模量的预测,大大节省研发和实验成本,加快高性能材料的筛选。
关键词:钛合金;第一性原理;机器学习;遗传算法;力学性能DOI:10.3969/j.issn.1674-6457.2024.01.004中图分类号:TG135+.1 文献标志码:A 文章编号:1674-6457(2024)01-0033-10Prediction Method of Elastic Modulus of Titanium Alloy Based on Machine LearningWANG Yuanyuan, WU Chuan*, PENG Zhiwei, SHI Wencai(National-local Joint Engineering Laboratory of Intelligent Manufacturing Oriented Automobile Die & Mould,Tianjin University of Technology and Education, Tianjin 300222, China)ABSTRACT: The work aims to improve the prediction accuracy of elastic modulus of titanium alloy through an efficient and feasible prediction method, and establish a high-precision prediction model which combines first-principle calculation and ma-chine learning. Through data mining, the microstructure parameters of mechanical properties of titanium alloy in the material database were obtained, and the initial data set was calculated and constructed based on the first principle, which was pretreated, including noise elimination, normalization and standardization, so as to obtain a high-quality data set. At the same time, the random forest characteristic importance analysis method was used to screen the input parameters and remove the weakly corre-收稿日期:2023-09-06Received:2023-09-06基金项目:国家自然科学基金(52075386);天津市自然科学基金多投入重点项目(22JCZDJC00650);中国博士后科学基金第67项研究基金(2020M672309);陕西省高性能精密成形技术与装备重点实验室项目(PETE2019KF02)Fund:National Natural Science Foundation of China (52075386); China-Multi-input Key Project of Tianjin Natural Science Foundation (22JCZDJC00650); Research Fund 67 of China Postdoctoral Science Foundation (2020M672309); Shaanxi Key Laboratory of High-performance Precision Forming Technology and Equipment (PETE2019KF02)引文格式:王园园, 武川, 彭志伟, 等. 基于机器学习的钛合金弹性模量预测方法研究[J]. 精密成形工程, 2024, 16(1): 33-42. WANG Yuanyuan, WU Chuan, PENG Zhiwei, et al. Prediction Method of Elastic Modulus of Titanium Alloy Based on Machine Learning[J]. Journal of Netshape Forming Engineering, 2024, 16(1): 33-42.*通信作者(Corresponding author)34精密成形工程 2024年1月lated variables to reduce the complexity of the prediction model. On this basis, a random forest model, a support vector machine model, a BP neural network model and an optimized GA-BP neural network model were constructed, and the optimal algorithm model was selected after comprehensive comparison of regression capacity of each model and error rate analysis. Finally, a pre-diction model for elastic modulus of titanium alloy was established, in which the correlation coefficient R of the random forest model, the support vector machine model, the BP neural network model and the optimized GA-BP neural network model was0.836, 0.943, 0.917, and 0.986. Through comparative analysis, the prediction error of elastic modulus of GA-BP models is basi-cally kept at 5%-7%, showing high prediction accuracy. It is found that genetic algorithm can optimize the weight and threshold of the BP neural network, so as to give higher prediction accuracy. This method can realize the prediction of elastic modulus of titanium alloy, greatly save the research and development and experimental costs, and is applicable to the selection of high-performance materials.KEY WORDS: titanium alloy; first principles; machine learning; genetic algorithm; mechanical property目前,我国正在积极推动高端装备领域的结构材料向高强度、轻量化、高可靠性和可持续性等方向发展。
两类带两个形状参数的三角Quasi-Bézier曲面陈军;周联【期刊名称】《农业机械学报》【年(卷),期】2013(44)6【摘要】Two kinds of bivariate basis functions with two shape parameters over the triangular domain were presented.The corresponding triangular surfaces inherited the most properties of classical triangular Bézier surface,and adjusted the shape by changing the value of shape parameters with the fixed control points.When the shape parameters were equal to some specified values,the new triangular surfaces degenerated to the triangular Bézie r surface.The obvious geometric significance of shape parameters made it easier for the designer to adjust the shape of new surfaces,even if when the boundaries of triangular surfaces were fixed.The numerical examples indicated that the new surfaces were valid and easy for operation.%构造了两种定义在三角域上带两个形状参数的二元Quasi-Bernstein基函数.与之相应的两类三角Quasi-Bézier曲面其性质与传统的三角Bézier曲面相仿.当形状参数取某些特定值时,三角Quasi-Bézier曲面就退化为三角Bézier曲面.在控制顶点固定时,三角Quasi-Bézier曲面的外形可以通过改变形状参数的值来进行调整.两个形状参数几何意义明显,便于操作,其中一个在3条边界曲线固定后仍能够调整曲面的外形.数值实例表明了这两类三角Quasi-Bézier曲面在调整外形时的有效性与便捷性.【总页数】6页(P263-268)【作者】陈军;周联【作者单位】宁波工程学院理学院,宁波315211;上海海事大学文理学院,上海201306【正文语种】中文【中图分类】TP391.72【相关文献】1.三角域上带形状参数的三次Bézier曲面 [J], 刘植;檀结庆;陈晓彦2.三角域上带形状参数的四次Bézier曲面 [J], 严兰兰;樊继秋;马力3.三角域上带两个形状参数的Bézier曲面的扩展 [J], 于立萍4.三角域上带形状参数的四次Bézier曲面 [J], 严兰兰; 樊继秋; 马力5.带形状参数的三次三角域Bézier曲面 [J], 查东东;刘华勇;王曾珍因版权原因,仅展示原文概要,查看原文内容请购买。
上册:立方体抗压强度cube strength 极限状态limit state ultimate state预制混凝土prefabricated concrete 现浇混凝土Cast-in-situ concrete预应力混凝土prestressed concrete 设计基准期design reference period设计使用年限design working life 收缩shrinkage双筋梁doubly reinforced section 轴心受压柱axially loaded column偏心受压柱eccentrically loaded column 偏心距eccentricity 恒荷载permanent load or dead load 活荷载variable load or live load组合系数combination reduction factor 准永久值系数quasi-permanent reducing coefficient结构重要性系数coefficient of structural importance 界限配筋balanced reinforcement超筋over-reinforced 适筋under-reinforced等效应力矩形equivalent stress block 最小配筋率minimum steel ratio 最大配筋率balanced steel ratio 截面有效高度effective depth双筋梁doubly reinforced section T形截面翼缘flangeT形截面腹板web 有效翼缘宽度effective flange width主压应力迹线trajectories of the principal compressive stress 斜裂缝diagonal crack腹筋transverse reinforcement; web reinforcement 箍筋ties or stirrups弯起钢筋inclined bars bent-up bars 斜拉破坏diagonal splitting剪压破坏shear compression 斜压破坏diagonal compression剪跨比shear span ratio 名义剪跨比generalized shear span配箍率transverse tie ratio 材料弯矩抵抗图diagram of bending resistance不需要面cut-off section 充分利用面fully-developed section充分利用点fully usable point of bar 理论截断点theoretical cutting point of bar实际截断点real cutting point of bar 锚固长度anchorage length 绑扎搭接binding lapped splice 钢筋表bar schedule连接区段connection sector 肋梁楼板结构girder-beam-slab structural system现浇楼板cast-in-place slab 预应力楼板pre-cast slab刚度rigidity 弯矩包络图moment envelope diagram ;ultimate moment diagram剪力包络图shear envelope diagram塑性铰plastic hinge无梁楼盖flat slab塑性内力重分布法plastic redistribution of stresses analysis method弯矩调幅法the method of amplitude modulation for bending moment CHAPTER 1Plain Concrete 素混凝土,Reinforced Concrete 钢筋混凝土,Prestressed Concrete 预应力混凝土,reinforcement steel bar 钢筋(也有人直接用bar,fiber),Portland cement 波特兰水泥Light-weight concrete 轻质混凝土,high-strength concrete 高强混凝土,Fiber reinforcedconcrete(FRC)纤维混凝土load 荷载,span 跨径,strain 应变,stress 应力,compression 压力,tension 拉力,moment 弯矩,torsion 扭矩,扭转thermal expansion coefficients 热膨胀系数,corrosion protection 防腐蚀,Fire resistance耐火,hollow floor 空心楼板,wall 墙面,girder 主梁,beam 横梁,column 柱,footing 基础allowable stress design method 允许应力法,ultimate strength design method 极限强度设计法,limit state design method 极限状态设计法,composite structure 混合结构CHAPTER 2smooth bar 光圆钢筋,deformed bar 螺纹钢筋,hot rolled bar 热轧钢筋,cold drawn bar冷拉钢筋,steel wires 钢绞线,heat treated steel bar 热处理钢筋stress-strain curve 应力应变曲线,yield plateau 屈服平台deformation 变形,deflection 挠度,yield strength 屈服强度,ultimate strength 极限强度,ductility 韧性,hardening 强化,cold drawn 冷拉,tempering treatment 回火,quenching treatment 淬火fatigue 疲劳,shrinkage 收缩,creep 徐变,crack 开裂,crush 压溃water-cement ratio 水灰比cubic compressive strength 立方体抗压强度,prismatic compressive strength 棱柱体抗压强度elasticity modulus 弹性模量(杨氏模量),secant modulus 割线模量,tangent modulus 切线模量,shear modulus 剪切模量,poisson’s ratio 泊松比uniaxial tension 单轴拉伸,biaxial loading 双轴加载,triaxial loading 三轴加载CHAPTER 3bond 粘结,anchorage 锚固,bar splicing 钢筋搭接,splitting 撕裂,crush 压溃,pull-out failure 刮出式破坏splice length 搭接长度,embedded length 埋置长度,development length 锚固长度shape coefficient 外形系数ribs 钢筋肋CHAPTER 4axial load 轴向加载,axial tension 轴向拉伸,axial compression 轴向压力elasticity 弹性,plasticity 塑性longitudinal bars 主筋(纵向钢筋),stirrup 箍筋,hanger bar 架立筋,bent bar 弯起钢筋brittle failure 脆性破坏,load carrying capacity 承载能力short column 短柱,slender column 长柱,stability coefficient 稳定系数cross section 截面,cross-sectional dimension 截面尺寸spiral stirrup 螺旋箍筋CHAPTER 5box section 箱形截面,hollow slab 空心板,T-section T 形截面over-reinforced beam 超筋梁,under-reinforced beam 少筋梁,balanced-reinforced beam适筋梁brittle failure 脆性破坏concrete cover 混凝土保护层minimum reinforcement ratio 最小配筋率flexure theory 弯曲理论,plane section assumption 平截面假定neutral axis 中性轴,coefficient 系数,parameter 参数,constant 常数stress distribution 应力分布,shear span ratio 剪跨比stress block depth 应力区高度(受压区高度),relative stress block depth 相对应力区高度(相对受压区高度),nominal stress block depth 名义应力区高度(名义受压区高度),flexural capacity 抗弯承载能力symmetry reinforcement 对称配筋effective flange width 有效翼缘宽度,flange 翼缘,web 腹板shear-lag effect 剪力滞效应simple-supported beam 简支梁,continuous beam 连续梁deep-bending member 深受弯构件,deep beam 深梁,transfer girder 转换梁,tie-reinforcement 拉结筋,horizontal distributing reinforcement 水平分布钢筋spacing 间距CHAPTER 6eccentricity 偏心率,second-order effect 二阶效应ultimate limit state 使用极限状态additional eccentricity 附加偏心距eccentricity magnifying coefficient 偏心距放大系数tensile failure 受拉破坏,compressive failure 受压破坏larger eccentricity 大偏心,small eccentricity 小偏心out-plane strength 片面外强度geometric central axis 几何中心轴CHAPTER 7shear failure 剪切破坏diagonal tension 斜向拉应力shear flow 剪力流diagonal cracks 斜裂缝,flexural crack 弯曲裂缝,compression strut 受压杆web reinforcement 腹筋(抗剪钢筋)truss model 桁架模型slope angle 倾角upper end of the crack 裂缝上端maximum spacing of stirrup 箍筋最大间距concentrated load 集中荷载,uniform load 均布荷载detailing requirement 构造要求moment envelope 弯矩包络图,moment diagram 弯矩图embedded length 锚固长度points of bend 弯起点CHAPTER 8equilibrium torsion 均衡扭转,compatibility torsion 协调扭转static equilibrium 静力平衡principal stress 主应力cracking torque 开裂弯曲transverse reinforcement 横向钢筋elasto-plastic mode 弹塑性模型Plastic space truss design method 塑性空间桁架设计方法,Skew bending design method斜弯设计方法hollow section 空心截面perimeter 周长hook 弯钩minimum stirrup ratio 最小配箍率distribution of reinforcement 钢筋分布CHAPTER 9punching shear 冲切,local compression 局部受压two way shear 双向剪切slab-column joint 板柱交接点column cap 柱帽,drop panel 托板linear interpolation 线形内插effective depth 有效高度critical width 临界宽度punching shear cone 冲压椎体polar moment of inertia 极惯性矩net area 净面积spiral stirrup 螺旋箍筋,mat reinforcement 钢筋网splitting 劈裂,chipping 崩裂CHAPTER 10prestressed concrete 预应力混凝土pretensioning system 先张法,post-tensioning system 后张法wire 钢丝,strand 钢绞线,tendon 钢束bottom 台座,casting-yard 预制场duct 孔道,jack 张拉,grout 灌浆,bond 粘结,unbond 无粘结friction 摩擦full prestressing 全预应力,partial prestressing 部分预应力creep 徐变,shrinkage 收缩stress loss 应力损失grippers 夹具,anchorage 锚具permissible stress 容许应力,stretching stress 拉伸应力,effective prestress 有效预应力loss of prestress 预应力损失,loss due to friction 摩擦损失,anchorage-sections 锚具滑移,elastic shortening of concrete 混凝土塑性回缩,steel stress relaxation 钢筋应力松弛,creep loss 徐变损失,shrinkageloss 收缩损失tendon profile 钢束形状,deviation force 偏向力,curvature effect 曲率效应,wobbleeffect 抖动效应fixed end 固定端,tension end 张拉端overstretching 超张拉curvature friction coefficient 曲率摩擦系数transfer length 传递长度,bond stress 粘结应力concrete depositing 混凝土浇注service stage 使用阶段,construction stage 施工阶段Transformed area 换算面积,moment of inertia 惯性矩hoisting 吊装,transporting 运输dynamic factor 动力系数ordinary reinforced steel 普通钢筋normal section 正截面,oblique section 斜截面CHAPTER 11serviceability 使用性能reliability 可靠性:safety 安全,applicability 实用,durability 耐久deflection 挠度,crack width 裂缝宽度transverse crack 横向裂缝,plastic crack 塑性裂缝,temperature crack 温度裂缝,shrinkage crack 收缩裂缝,cracks due to rust 锈蚀引起的裂缝,cracks due to differential settlement 不均匀沉降引起的裂缝,load-induced crack 荷载引起的裂缝freezing-thawing 冻容,alkali-aggregate reaction 碱骨料反应standard value 标准值,frequent value 频遇值,quasi-permanent value 准永久值maximum crack width 最大裂缝宽度crack control 开裂控制bond-slip theory 粘结滑移理论,non-slipping theory 无滑移理论flexural stiffness 弯曲刚度__。
a r X i v :0809.0673v 1 [a s t r o -p h ] 3 S e p 2008Quasi-equilibrium models for triaxially deformed rotating compact starsXing Huang,1Charalampos Markakis,1Noriyuki Sugiyama,1and K¯o ji Ury¯u 21Department of Physics,University of Wisconsin-Milwaukee,P.O.Box 413,Milwaukee,WI 532012Department of Physics,University of the Ryukyus,Senbaru,Nishihara,Okinawa 903-0213,Japan(Dated:September 3,2008)Quasi-equilibrium models of rapidly rotating triaxially deformed stars are computed in general relativistic gravity,assuming a conformally flat spatial geometry (Isenberg-Wilson-Mathews for-mulation)and a polytropic equation of state.Highly deformed solutions are calculated on the initial slice covered by spherical coordinate grids,centered at the source,in all angular directions up to a large truncation radius.Constant rest mass sequences are calculated from nearly axisym-metric to maximally deformed triaxial configurations.Selected parameters are to model (proto-)neutron stars;the compactness is M/R =0.001,0.1,0.14,0.2for polytropic index n =0.3and M/R =0.001,0.1,0.12,0.14for n =0.5.We confirmed that the triaxial solutions exist for these parameters as in the case of Newtonian polytropes.However,it is also found that the triaxial sequences become shorter for higher compactness,and those may disappear at a certain large com-pactness for the n =0.5case.In the scenario of the contraction of proto-neutron stars being subject to strong viscosity and rapid cooling,it is plausible that,once the viscosity driven secular instabil-ity sets in during the contraction,the proto-neutron stars are always maximally deformed triaxial configurations,as long as the compactness and the equation of state parameters allow such triaxial sequences.Detection of gravitational waves from such sources may be used as another probe for the nuclear equation of state.I.INTRODUCTIONRapidly rotating compact objects are expected to be formed as new born neutron stars after stellar core collapses,or as differentially rotating hypermas-sive neutron stars after binary neutron star merg-ers.Accretion onto neutron stars in X-ray binaries can also lead to rapid rotation.All of these have been extensively studied as strong sources of gravita-tional waves for the ground based laser interferometers LIGO/GEO600/VIRGO/TAMA (See e.g.[1]and refer-ences therein).Classical models of rotating stars are a class of ellip-soidal figures of equilibrium;self-gravitating rotating in-compressible fluids in Newtonian gravity.Such solutions include sequences of axisymmetric Maclaurin ellipsoids,or non-axisymmetic Jacobi,Dedekind,or Riemann S-type ellipsoids [2].These models are used to study the secular evolutions of rapidly rotating stars due to the viscosity and the radiation back-reaction of gravitational waves [3].Lai and Shapiro [4]have developed an ellip-soidal approximation to the rotating polytropes,and ap-plied the model to clarify the secular evolution of rapidly rotating neutron stars in detail,and more recently fo-cused on the viscosity driven secular instability [5].As discussed in [1,3,4],and shown by a number of numerical simulations of rapidly rotating compact stars,core collapse,and binary neutron star mergers [6,7,8],a transient triaxially deformed compact object may sur-vive within a secular time scale.In this paper,we con-sider uniformly rotating models of such triaxially de-formed compact objects,an extension of the Jacobi el-lipsoid in general relativity.In Newtonian gravity,such solutions exist for rotating polytropes with polytropic in-dex n <0.808[9].Here,the polytropic equation of state(EOS)p =κρ1+1/n relates the pressure p with the baryon rest mass density ρ.In general relativity,such configurations are not in equilibrium due to the back-reaction of gravitational ra-diation.However as in the case of quasi-equilibrium ini-tial data of binary neutron stars,triaxially deformed uni-formly rotating stars are in quasi-equilibrium,as long as the gravitational luminosity is small enough that the en-ergy radiated away within a rotational period is small compared to the binding energy of the star,which is al-ways the case,and if the viscosity is strong enough for the flow field to become uniformly rotating during the evolution.Therefore,as an important application,a se-quence of uniformly rotating quasi-equilibrium solutions may model a secular evolution from the proto-neutron star to the neutron star in the strong viscosity limit,and each solution may serve as the initial data for the general relativistic hydrodynamic simulations of such objects.Models of rapidly rotating neutron stars have been extensively studied as stationary,axisymmetric,perfect-fluid spacetimes [10],while less attention has been paid to uniformly rotating triaxial solutions,not only because they are not exact equilibria due to gravitational radia-tion reaction,but also because,in early calculations [11],models of the EOS above nuclear density did not allow large enough values of T/|W |∼0.14where a triaxial sequence is expected to bifurcate from an axisymmet-ric sequence.Here,T/|W |is the ratio of kinetic en-ergy T to gravitational potential energy W .However,as seen,for example,in [12],a value n ∼0.5(an effec-tive adiabatic index Γ∼3)may be possible for recent models of EOS for high density nuclear matter,aboveρ>ρnuc ∼2×1014g /cm 3,and,as we will see below,tri-axial quasi-equilibrium solutions do exist even in strong gravity for relatively small polytropic indexes,such as2 n=0.5or n=0.3,as in the Newtonian case.About a decade ago,Nozawa succeeded in comput-ing uniformly rotating triaxial polytropes in general rel-ativistic gravity in his thesis[13],although his cal-culations were limited by the computational resourcesto low resolutions.A few studies approximating thefluid as an ellipsoidal configuration in general relativisticgravity have been made[14],and perturbative analyseshave located the bifurcation point suggesting the exis-tence of solutions having triaxial bar-mode deformations[15,16,17,18,19,20].Our computations of triaxially de-formed stars can be used to locate the instability pointson the axisymmetric sequence as well as to estimate thegravitational wave amplitude and luminosity from suchobjects.In this paper,we present ourfirst results on triax-ial configurations of rapidly rotating general relativisticstars as models of neutron stars in extreme rotation.We assume a conformallyflat spatial slice,and solve theconstraints and spatial trace of the Einstein equation (Isenberg-Wilson-Mathews(IWM)formulation)[21,22] 1.This is different from the formulation used by Nozawa [13]in which the line element is chosen to be the sameform as that of stationary axisymmetric spacetime,but an azimuthal dependence is allowed(see[25]for the same formulation).The formulations and the code are de-scribed in the next section.For testing the code,selected axisymmetric solutions are compared with the results in the literature,and the bifurcation points of axisymmet-ric and triaxial sequences in weak gravity are examined. Then,we present the results of deformation sequences of constant rest mass systematically in the range of two parameters,the compactness M/R and the polytropic index n,appropriate for realistic neutron stars.Appli-cations of such triaxial solutions in the contraction of a newly born proto-neutron star are briefly discussed in thefinal section.Throughout the paper,we use units such that G=c=1.For our tensor notation,we adopt the use of Greek letters for spacetime indices,and Latin letters for spatial indices.II.FORMULATION AND NUMERICALMETHODA.IWM formulationThe IWM formulation for computing spatially con-formallyflat initial data we use for computing non-axisymmetric quasi-equilibrium of rotating compact star is briefly described.The spacetime M=R×Σis foliated by the family of spacelike hypersurfacesΣt={t}×Σ. The future-pointing timelike normal nαtoΣt is related2α∂tγab+12nαnβ =0,(5)where thefirst and second equations are the constraints. These equations are written in the form of elliptic equa-tions with the non-linear source terms,respectively,◦∆ψ=−ψ53K2 −2πψ5ρH,(6)◦∆˜βa+1α+48A ab A ab+52α £βf ab−12α ◦D a˜βb+◦D b˜βa−23 where£βdenotes the Lie derivative with respect toβa.Thefield equations Eqs.(6)-(8)are thus rewritten◦∆ψ=−ψ53◦D a◦D b˜βb=−2αA a b◦D b lnψ68αψ5A ab A ab+2παψ5(ρH+2S).(13)Eq.(12)is decomposed further to improve the accuracy in numerical computation.Following the decomposition proposed by Shibata[26],we write Eq.(12)as◦∆˜βa+18◦D a(B−x b B b),(15)where x a are coordinates that satisfy◦D a x b=δa b.Sub-stituting the decomposition(15)into Eq.(14)yields◦∆˜βa+16◦D a(◦∆B−x b◦∆B b)=S a.(16)The elliptic equations◦∆B a=S a and◦∆B−x b◦∆B b=0 are separated,and the former is substituted to the latter:◦∆B a=S a:=−2αA a b◦D b ln ψ6√−g)=0.(22)Consequently,the conservation of specific entropy alongthefluid world line,uα∇αs=£u s=0,(23)and,the relativistic Euler equations,uβ∇β(huα)+∇αh=£u(huα)+∇αh=0,(24)are obtained.Assuming theflowfield to be isentropiceverywhere inside the neutron star matter,s=const,wehave a one-parameter equations of state(EOS)p=p(ρ).We assume a stationary state in the rotating frame forthefluid source.Imposing symmetry along the helicalvector kα=tα+ΩφαwhereΩis a constant angularvelocity of a rotating frame,we have£k(ρu t√u t=E=constant,(26)where E is the injection energy.From the normalizationof the four velocity uαuα=−1,one obtainsu t=1α2−ωaωa=1α2−ψ4f abωaωb,(27)whereωa=βa+Ωφa.As afirst step in the calculation of a highly deformedtriaxial compact star,we assume a simple polytropicEOS,p=κρ1+1/n,(28)whereκis a constant,and n is the polytropic index.Then h is related to p/ρbyh=1+(n+1)p4source terms,are similar to the ones used in a previ-ously developed initial data code for binary black holes and neutron stars[27,28].However,the code itself has been completely rewritten,so that further extensions can be incorporated easily.One of the revisions of the code is that no symmetry is a priori assumed on the spatial sliceΣ0;that is,the spherical coordinate grids centered at the source cover all angular directions,up to a certain large truncation radius.Hence,for example,asymmet-ric magneticfields may be later included without major modifications to the putation of binary solu-tions using the same coordinate setup is also possible. The other major change is a simpler,more robust choice offinite differencing.In this section,we briefly describe the necessary steps for constructing the code,which are 1.Spherical coordinates and the length scale,2.Sum-mary of variables and equations for coding,3.Poisson solver,4.Grid spacing,5.Finite differencing and itera-tion,putation of a sequence of solutions.1.Spherical coordinates and the length scaleThe sliceΣ0is covered by a spherical coordinate patch (r,θ,φ)∈[r a,r b]×[0,π]×[0,2π].For a single star calcula-tion,the radial coordinate extends from the center of the star r=r a=0to the asymptotic radius r=r b=104R0, where R0is the radius of the neutron star along the semi-major axis,defined by theθ=π/2andφ=0,πlines.We also refer to Cartesian coordinates(x,y,z)whose pos-itive x,y and z directions are along(θ,φ)=(π/2,0), (π/2,π/2)andθ=0,respectively.The quantity R0is introduced as an additional param-eter in the formulation used in our code,normalizing the radial coordinate asˆr=r/R0.(30) For a polytropic EOS,one can rescale the length using the polytropic constantκasκ−n/2R0,or simply setting κ=1(see e.g.[27]).As a result,we have three parame-ters{Ω,E,R0}in our formulation.Furthermore,we introduce surfacefitted coordinates on which thefluid variables are defined.Assuming that the surface of a neutron star can be described by a func-tion of the angular coordinate R(θ,φ)=R0ˆR(θ,φ),the surfacefitted coordinates(ˆr f,θf,φf)are defined byˆr f:=ˆr/ˆR(θ,φ),θf=θ,φf=φ,(31) whereˆr f is defined in a regionˆr f∈[0,1].2.Summary of variables and equations for codingAs mentioned in Sec.II A,thefield equations(11), (13),(17)and(18)are solved for the metric potentials {ψ,αψ,B a,B}and,as in Sec.II B and II C1,a comoving fluid in equilibrium is characterized by onefluid variable,which is chosen to be the relativistic enthalpy{h},and three parameters{Ω,E,R0}.Thefield equations are normalized to have the fol-lowing form;representing each of the metric potentials {ψ,αψ,B a,B}byΦ,◦∆Φ=S g+R20S m,(32)where theflat Laplacian◦∆corresponds now to the nor-malized coordinateˆr.The source term S g includes the metric potentials and their derivatives,while S m also in-cludes the matter variables and the parameters{Ω,E}, while the dependence on the length scale R0is explicitly separated in Eq.(32).Thefluid variable{h}is determined by Eq.(26)cou-pled to the EOS(28),and the relations(27)and(29). The three parameters{Ω,E,R0}are determined by the following three quantities:the surface radii along two of the three semi-major axes,and the value of the central density.These quantities are used to impose three con-ditions on Eq.(26),which are solved with respect to the three parameters{Ω,E,R0}in each iteration cycle.3.Poisson solverThe elliptic equations(11),(13)(17),and(18)are inte-grated on the spherical grid using Green’s formula.Rep-resenting each of the potentials{ψ,αψ,B a,B}byΦ,the latter is given byΦ(x)=−14π ∂V[G(x,x′)∇′aΦ(x′)−Φ(x′)∇′a G(x,x′)]dS′a.(33) where x and x′are positions,x,x′∈V⊆Σ0.We choose the Green function G(x,x′)without boundary,◦∆G(x,x′)=−4πδ(x−x′),(34) and perform a multipole expansion in associated Legen-dre functions,G(x,x′)=1(ℓ+m)!×P mℓ(cosθ)P mℓ(cosθ′)cos m(ϕ−ϕ′),(35) where the radial Green function gℓ(r,r′)is defined bygℓ(r,r′)=rℓ<5TABLE I:Summary of grid parameters.4.Grid spacingThefield equations in the integral form(33)are dis-cretized on the spherical grids,and iterated until con-vergence is achieved.Our code allows us to use any non-equidistant grid spacing in all the spatial coordi-nates,(r i,θj,φk),i=0,···,N r,j=0,···,Nθ,and k=0,···,Nφ.The radial grid points are equidistant in the region[r a,r c]and non-equidistant in[r c,r b],as follows:writing∆r i:=r i−r i−1,we have∆r i=∆r=r c−r ak−1∆r.(39)We choose equidistant grid spacing forθj andφk,that is,∆θi=∆θ=π/Nθ,and∆φi=∆φ=2π/Nφ.Our notations for the grid points are summarized in Table I.5.Finite differencing and iterationFor the numerical integration of Eq.(33)we select the mid-point rule.Accordingly,source terms are evaluated at the middle of successive grid points.The linear inter-polation formula and the second order Lagrange formula are applied for computing the source termfields and their derivatives respectively,at the mid-points of the r,θand φgrids.The reason for selecting a rather low(second)order finite difference scheme is the following:When thefield quantities vary rapidly,such as at a density discontinuity in a neutron star,higher order interpolating formulas as well asfinite difference formulas tend to overshoot near the region,and may cause a non-convergent iteration. To overcome this behavior,one may either(i)separate the computing regions at the discontinuity,or(ii)use lower order polynomial approximations.With thefirst approach,pseudo-spectral methods have been success-fully implemented by[29]and achieved an evanescent error.We select the second idea to keep the code as sim-ple andflexible as possible,and improve the accuracy by simply increasing the number of grid points.In each iteration cycle,the Poisson solver(33)is called for each variable.Writing the L.H.S.of Eq.(33)asˆΦ, eachfield variable is updated from the N th iteration cycle to the(N+1)th in the mannerΦ(N+1)=λˆΦ+(1−λ)Φ(N),(40) where the softening parameterλis chosen to be0.3∼0.5 for accelerated convergence.Then we check the relative difference of successive cycles2|Φ(N+1)−Φ(N)|6I-101041.25602016244812I-201041.25903024367212I-301041.251204032489612I-401041.2518060487214412I-501041.2524080649619212TABLE II:Coordinate parameters,and the number of grid points with different resolutions.L is the highest multipole included in the Legendre expansion.polytropic EOS,one can normalize these quantities by a certain power of the polytropic constant κ,as shown in the same Appendix.Hence we choose κ=1units to present solution sequences.A sequence of solutions with constant rest mass is con-sidered as an evolutionary track of adiabatic changes in quasi-equilibrium.Under this assumption,the solutions in each sequence are parameterized by the angular veloc-ity Ω,and the first-law relationδM ADM =ΩδJ(42)is satisfied,as proved in [32].III.CODE TESTA.Axisymmetric solutionsAxisymmetricsolutions calculated by ournew codeare compared with the results in the literature [23,33].We show the results of comparisons for models presented in Table I of Cook,Shapiro and Teukolsky [23](here-after CST),which correspond to a solution sequence with constant rest mass M 0=0.14840for the case with the polytropic index n =0.5.This value of M 0is close to the maximum rest mass of a non-rotating spherical so-lution;the gravitational mass and the compactness of the same non-rotating solution are M =0.12304and M/R =0.29605.In Table III,selected solutions calcu-lated with the highest resolution I-5in Table II are com-pared with the results shown in Table I of [23].Fractional errors in any quantities are less than 0.5%.As discussed in the section II C 5,our choice of finite difference approximations is second order.The rate of convergence of our code is checked using different resolu-tions,whose setups of coordinate grids are shown in Table II.The grid spacing of each coordinate (∆r,∆θ,∆φ)is proportionally scaled as 2/3,3/4,2/3,3/4,from type I-1to I-5.Here,we show the results of the convergence test with respect to the resolutions,fixing the maximumPresent 0.46140.52520.12470.042810.7911CST 0.45920.52320.12470.042530.7911Present 0.75810.72220.12810.13100.5614CST 0.75850.72140.12840.13140.56141−(¯Rz /¯R x )2where the radii ¯Rx ,¯R z along the x and z axes are measured in proper length as in Eq.(A11).number of multipoles L as shown in Table II.2.When a sufficient number of multipoles is kept,the dif-ferences between numerically computed quantities with different resolutions and their exact value are writtenf I -i −f exact =A ∆n I -i +O (∆n +1I -i )(43)where f I -i (i =1,···,5)is a quantity computed using one of the resolution types I-i in Table II,f exact is its exact value,∆I -i represents the grid spacing associated with the type I-i setup,and A is a constant.Then,keeping the leading term,differences between different resolutions becomef I -k −f I -i =A∆I -k2For the convergence tests with respect to the order of the Leg-endre expansion,see [28]710-210-1100e r r o r [%]FIG.1:The convergence of quantities,Ω,M ADM ,J ,T /|W |and e :=p8-1.00.01.0-1.00.01.0z /R 0x/R-1.00.01.0-1.00.01.0z /R 0y/R 0-1.00.01.0-1.00.01.0y /R 0x/R 0FIG.3:Contours of the p/ρon xz -plane (top left panel),on yz -plane (top right panel),and on xy -plane (bottom left panel)are shown for the most deformed triaxial model of n =0.3and M/R =0.2.Contours are drawn linearly from 0.0to 0.1every 0.01step.gest that the value of T/|W |at the bifurcation point strongly depends on compactness M/R .In Table IV,approximate values of quantities at the bifurcation point of each model are shown,which are evaluated by linearly extrapolating the triaxial sequence to the corresponding axisymmetric sequence.The value of T/|W |at the bi-furcation point becomes ∼0.169for the compact model M/R =0.2,n =0.3,and it will certainly increase for a more compact sequence.As seen in the plot of Fig.5,the triaxial solution se-quence for n =0.5becomes shorter as M/R increases.In fact,we were not able to find a triaxial solution sequence for M/R =0.2;the triaxial sequence may disappear at a certain value of M/R between 0.14-0.2.We discuss an interesting consequence of the disappearance of triaxial sequences for high compactness in the last section.V.DISCUSSION:PROTO-NEUTRON STARCONTRACTIONAs a result of massive stellar core collapses,proto-neutron stars are formed and contract to more compact neutron stars within the time scale of cooling of a few tens of seconds [36].Even for the small rotation rate of the col-lapsing stellar core,the ratio T/|W |of the proto-neutron star becomes much higher than the value where the ax-isymmetric solution becomes secularly unstable against the viscosity driven ℓ=m =2bar mode instability [4,5].Therefore,uniformly rotating triaxial solutions discussed in this paper may describe a quasi-stationary model of proto-neutron star contraction in the range of M/R ∼0.1−0.2,assuming the following:(1)a cer-tain mechanism of strong viscosity operates during theT /|W |ΩMFIG.4:Plots for T /|W |(top panel)and ΩM (bottom panel)versus eccentricity e :=p90.30.10.3226(0.3718)0.5634(0.5693)0.38880.65292.8444×10−28.794×10−40.15071.347×10−30.13280.30.140.3435(0.4220)0.5531(0.5619)0.44450.71614.4203×10−21.903×10−30.15782.657×10−30.20190.30.20.3561(0.4860)0.5394(0.5535)0.52440.80636.9865×10−24.351×10−30.16885.395×10−30.33110.50.10.5153(0.5919)0.5461(0.5536)0.20590.43914.2103×10−21.913×10−30.14934.356×10−30.12810.50.120.5209(0.6169)0.5439(0.5531)0.23190.46985.2155×10−22.753×10−30.15195.861×10−30.15940.50.140.5314(0.6482)0.5366(0.5482)0.25810.49956.2304×10−23.734×10−30.15427.476×10−30.19323In their work,changes in the entropy during the evolution is mod-eled by the changes in the adiabatic constantκof the polytropicEOS.10source is within a few tens of Mpc [4,18].Detection of the persistent GW signals even after the proto-neutron star contraction phase suggests a large effective Γ 3,while the shutdown of the signal during the contraction implies the relatively smaller Γ 3.Detection of such GW sig-nal may set another constraint on the EOS parameter of high density matter.Source modeling for constructing the wave templates may be straightforward because one can concentrate on calculating the maximally deformed configurations.Our next plan is to include more realis-tic nuclear EOS in the code,then to estimate the grav-itational wave amplitude for those EOSs that allow the triaxial solutions.AcknowledgmentsWe would like to thank John Friedman for discus-sions and warm encouragement.KU thanks YoshiharuEriguchi for discussions and for providing a reprint of PhD thesis by Tetsuo Nozawa,and Shin Yoshida for discussions.This work was supported by NSF grants No.PHY0071044,PHY0503366,NASA Grant No.NNG05GB99G,the Greek State Scholarships Founda-tion,and JSPS Grant-in-Aid for Scientific Research(C)20540275.APPENDIX A:FORMULAS FOR MASS ANDANGULAR MOMENTUMDefinitions of the quantities shown in tables and figures that characterize each solution of a rotating relativistic star,and their expressions in terms of the metric poten-tials in the IWM formulation,are summarized in this Appendix.The rest mass of the star M 0is written asM 0:= Σρu αdS α= Σρu t αψ6−gd 3x and√fd 3x =αψ6r 2sin θdrdθdφ.The ADM mass M ADM becomesM ADM :=12π∞◦D a ψd ◦S a =−12π Σ1fd 3x,(A2)where d ◦S a =∇a r √fd 3x ,and dS acoincides with d ◦S a at spatial infinity.The Komar mass associated with a timelike Killing field t αis writtenM K :=−14πΣR αβt βdS α=Σ(2T αβ−T g αβ)t βdS α,(A3)and,in the IWM formulation,we haveM K =Σ[α(ρH +S )−2j a βa ]ψ6γd 3x was used.The above derivationholds if the global timelike Killing field exists.For the spacetime of a triaxially deformed rotating star,no such timelike Killing field exists.Instead,an asymptotic Ko-mar mass can be writtenM K :=−14π∞D a αdS a =14π Σα˜A ab ˜A ab +4πα(ρH +S ) ψ68π∞πa b φb dS a =18πΣD a (K a b φb )dS(A6)=1fd 3x.(A7)The relativistic analog of the kinetic energy T is de-fined byT :=12ΩJ .Alsothe relativistic analog of the gravitational potential en-ergy W is defined byW :=M p +T −M ADM ,(A9)where M p is the proper mass defined byM p :=Σǫu αdS α= Σǫu t αψ611where R x is the coordinate length of the same axis.The proper lengths along the y or z directions are calculated using the same formula,replacing x by y or z respectively. In the above,the source terms of thefield equations,ρH,j a,and S,are obtained from the stress energy ten-sor.We write down the projection of the stress tensor in terms of elementaryfluid variables and metric poten-tials.The4-velocity for the corotationalflow uα=u t kαis decomposed with respect to the foliationΣt asuαnα=−αu t(A12)uαγαa=u tωa.(A13) Using these relations,the source terms of thefield equa-tions becomeρH:=Tαβnαnβ=hρ(αu t)2−p,(A14)j a:=−Tαβγaαnβ=hρα(u t)2ψ4˜ωa,(A15)S:=Tαβγαβ=hρ (αu t)2−1 +3p,(A16)where˜ωa:=f abωb=f ab(βb+Ωφb)=˜βa+Ω˜φa. 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