Chemical Enrichment at High Redshifts Understanding the Nature of Damped Ly$alpha$ Systems
Use of the axial dispersion model to describe

Use of the axial dispersion model to describe the O 3and O 3/H 2O 2advanced oxidation of alachlor in waterFernando J Beltra´n,*Manuel Gonza ´lez,Benito Acedo and Javier Rivas Departamento de Ingenieria Quı´mica y Energe ´tica,Universidad de Extremadura,06071Badajoz,Spain Abstract:Experiments on alachlor degradation by ozonation alone and combined with hydrogenperoxide using different surface waters have been conducted in a reactor bubble column and a kinetic model of the advanced oxidation process has been proposed.Variables studied were the nature of the surface water (four surface waters were treated),pH (3.5±9.7)and hydrog en peroxide to ozone mass ratio at the column inlet (0.1±1.85gg À1).Data on residence time distribution,rate constants and the absorption kinetic reg ime were considered to prepare the kinetic model,which was also based on the axial dispersion model of non-ideal ¯ow.The model gives good predictions of alachlor and hydrogen peroxide conversions and the fraction of dissolved ozone (deviations were lower than Æ15%)although it fails,in some cases,to yield accurate estimates of the observed experimental trends of concentrations in water at the reactor column outlet.The calculated results were close to those obtained from the more classical N well-mixed tanks-in-series model (deviations with this model were lower than Æ20%).It is concluded that quantitative deviations from experimental observations were likely due to the lack of rate data on ozone reactions with organic matter present in the surface waters investigated.#2002Society of Chemical IndustryKeywords:Alachlor;ozone;hydrogen peroxide;advanced oxidation;residence time distribution;kinetic modelling;surface water NOTATIONC g Ozone concentration in the gas (mol dm À3)C gH Ozone concentration in the gas at the bottom of reactor column (mol dm À3)C H 2O 2,H Concentration of hydrogen peroxide in water at the bottom of reactor column (mol dm À3)C H 2O 2,0Concentration of hydrogen peroxide in water at the top of the column (mol dm À3)C j Concentration of species j in water (mol dm À3)C M Concentration of compound M in water (mol dm À3)C O 3Ozone concentration in water (mol dm À3)C O 3,HOzone concentration in water at the bottom of reactor column (mol dm À3)C *O3Ozone concentration at the gas±water interface (mol dm À3)C OM Concentration of organic matter in water (mol dm À3)C 1,H Concentration of alachlor in water at the bottom of reactor column (mol dm À3)C 1,0Concentration of alachlor in water at the top of the column (mol dm À3)D jAxial dispersion coef®cient for species j in the water (m 2s À1)D G j Axial dispersion coef®cient for species j in the gas (m 2s À1)D O 3Ozone diffusivity in water,(m 2s À1)h Height of reactor column at a given position (m)H Total height of reactor column (m)H a Hatta number for an irreversible second order gas±liquid reaction (dimensionless)He Constant of Henry for the ozone±water system (Padm 3mol À1)k c Rate constant de®ned in eqn (22)(dm 3mol À1s À1)k L Individual liquid side mass transfer coef®cient (m s À1)k L a Volumetric mass transfer coef®cient (s À1)N Number of continuous perfectly mixed tank reactors in series (dimensionless)N O 3Ozone absorption rate (mol dm À3s À1)Pe L Peclet number for the liquid phase,de®nedas u L HD À1j(dimensionless)Pe G Peclet number for the gas phase,u G HD À1G j (dimensionless)Q g Gas ¯ow rate (m 3s À1)R Constant of ideal gases (Padm 3mol À1K À1)r jNet reaction rate of species j in water,eqns (24)or (25)(mol dm À3s À1)(Received 13March 2001;revised version received 6December 2001;accepted 21December 2001)*Correspondence to:Fernando J Beltra´n,Departamento de Ingenieria Quı´mica y Energe ´tica,Universidad de Extremadura,06071Badajoz,SpainE-mail:fbeltran@unex.esContract/grant sponsor:CICYT of Spain;contract/grant number:1FD97/2222/CO3/02Journal of Chemical Technology and BiotechnologyJ Chem Technol Biotechnol 77:584±592(online:2002)DOI:10.1002/jctb.613r O 3Reaction rate of ozone decomposition inwater (mol dm À3s À1)S Sectional surface of bubble column (m 2)t Time (s)T Temperature (K)u G Velocity of the gas phase (m s À1)u L Velocity of the water phase (m s À1)V Total volume of bubble column (m 3)w Parameter de®ned in eqn (21)(dimensionless)X 1,H Alachlor conversion at the reactor column outlet,de®ned as (C 1,0ÀC 1H )/C 1,0(dimensionless)X H 2O 2,H Hydrogen peroxide conversion at the reactor column outlet de®ned as(C H 2O 2,0ÀC H 2O 2,H )/C H 2O 2,0(dimensionless)z Stoichiometric ratio of the reaction between ozone and alachlor (dimensionless)a Parameter representing C H 2O 2,H ,X 1,H or c O 3,H in Figs 4and 5b Liquid hold-up (dimensionless)z j Parameter de®ned in eqn (31)(dimensionless)Z O 3Net dimensionless rate of ozone mass transfer to water,eqn (28)l Dimensionless height of reactor column at a given point,de®ned as h/Hx j Parameter de®ned in eqn (29)or (30) 2 Dimensionless variance of residence time distribution functiont G Hydraulic residence time of the gas phase through the bubble column(s)t L Hydraulic residence time of the water phase through the bubble column(s)c g Dimensionless concentration of ozone in the gas phase,de®ned as C g /C gHc jDimensionless concentration of species j in water,de®ned as C O 3/C gH for ozone,and C j /C 1,0for any other speciesc O 3,H Dissolved ozone fraction at the reactor column outlet,de®ned as C O 3,H /C gH (dimensionless)o jReaction rate of species j in dimensionless form,eqn (29)1INTRODUCTIONIn a previous paper,the high reactivity of alachlor (2-chloro-2',6'-diethyl-N -(methoxymethyl)acetanilide)with ozone,UV radiation and hydroxyl free radicals was shown.1This herbicide is widely used in agricul-ture and,as a result,it has been found in many natural water environments.2,3Alachlor is an important water pollutant with a very low maximum contaminant level (MCL)in drinking water as established by the USEPA (0.2m gdm À3)and the European Commission (0.1m gdm À3).4As reported previously,5,6ozonation and other chemical oxidations involving combinations of ozone,UV radiation and/or hydrogen peroxide (also called advanced oxidation processes,AOP),at suitable conditions,can remove alachlor from water to achieve the environmentally advisable limits.In a previous paper 1rate constants of the reactions between ozone and hydroxyl radical with alachlor were obtained.Before the practical application of AOP to remove alachlor and other pollutants from water,it is recommended that kinetic modelling be studied.Kinetic modelling of AOP has been previously performed for a range of compounds,as shown in Table 1.These models allow prediction of the performance of AOP under well de®ned conditions of oxidant and/or UV intensity doses,¯ow rates,concentration of pollutants,etc.In most cases,kinetic data are applied to mass balance equations under conditions of ideal ¯ow behavior for both the water and gas (if any)phases put into contact through the reactor used.Reactors in which experiments have so far been conducted are assumed to behave as idealTable 1.Examples of studies on kinetic modelling of AOPsOxidizing system Experimental conditionsReactor typeMethod of oxidation ReferenceOzonation±AH a 0.1±1.3%O 3(v:v),gas ¯ow rate:25dm 3h À1,C M0=3Â10À5±5Â10À6mol dm À3,pH=7SCMBR dHeterogeneous 7O 3/H 2O 2±ClHC bC O 3/C H 2O 2ratio:0±1.48(w:w),ozone dose:0.23±2.64mgdm À3min À1pH=5.3±10,C HCO 3=0±6mmol dm À3,C ClCH =50±70m gdm À3SCMBR d ,V =70dm 3Heterogeneous8O 3/UV±ClHC b C ClCH =100±600ppb,C O 3=10À4-2Â10À3mol dm À3,pH=6.9,I 0=2±20W m À2,T =283±303KCTDR e ,dimensions:30Â3Â200mm 3Homogeneous 9H 2O 2/UV-DBCP cC M0=1±3m mol dm À3,pH=5.4±10.4,C H 2O 20=0.05±6.6mmol dm À3,I 0=0.3±1.04Â10À6Einsteindm À3s À1h CMBR f ,V =70dm 3Homogeneous 10PhotoFenton-aromaticspH=2.8,C Fe(II)=0.05mmol dm À3,C M0=2mmol dm À3,C H 2O 2=0±8mmol dm À3,I 0not given (300±480nm and dark reaction)QCR g V =3cm 3,1cm pathHomogeneous11aAH:Aromatic hydrocarbons.bClHC:Chlorohydrocarbons.cDBCP:1,2-Dibromo-3-chloropropane.dSCMBR:Semicontinuous completely mixed batch reactor.eCTDR:Continuous tubular two-dimensional reactor.fCMBR:Completely mixed batch reactor.gQCR:Quartz cell reactor.hFor 254nm wavelength.Kinetic modelling of AOP alachlor removal from surface waterunits(perfect mixing or plug¯ow for water and gas phases).However,the actual situation differs in many instances and,at least,the¯ow of one of the two phases is non-ideal.Thus,a more rigorous approach to model the kinetics of AOPs is needed.This could be achieved by considering the actual¯ow or the non-ideal¯ow through the reactor.In this sense,a study of the residence time distribution function,RTDF,12of liquid and gas¯owing phases,is also required to be considered in the kinetic model. Inthispaperakineticmodeloftheadvancedoxidation of alachlor in water is presented by considering rate and non-ideal¯ow information.Calculated data from this model were then compared with experimental results. Two AOP systems were investigated:ozonation alone, and combined with hydrogen peroxide.2EXPERIMENTALOne glass bubble column(200cm long,4.15cm id) was used for the experiments.1The column was provided with a porous plate at the bottom to feed an oxygen±ozone gas stream(¯ow rate:20dm3hÀ1) and worked in continuous mode,the water(contain-ing the herbicide)(¯ow rate:0.25dm3minÀ1)and gas being fed countercurrently at the top and bottom of the column,respectively.Non-ideal¯ow experiments were carried out by using ozone and methylene blue as gas and liquid tracers,respectively.12Details of tracer experiments can be seen elsewhere.13Alachlor oxidation experi-ments were carried out in natural waters taken from the sources presented in Table2.The volumetric mass transfer coef®cient was deter-mined from physical ozone or oxygen absorption experiments in water following a method well described in the literature.14In the ozone experiments water at pH2was used to avoid any decomposition of ozone.The results obtained,once oxygen and ozone diffusivities were accounted for,were similar.In this way,the average value of the volumetric mass transfer coef®cient was found to be3.7Â10À3msÀ1. Methylene blue was analyzed colorimetrically in a Hitachi U-2000spectrophotometer by measuring the absorbance at600nm.Oxygen concentration,for physical absorption experiments,was determined with a58YSI oxygen meter.Alachlor was analyzed by liquid chromatography(HPLC)using a15cm long, 3.9cm id C18Novapack column and a486Waters UV/ visible detector.The mobile phase was an acetonitrile/ water mixture(40:60v/v)and the system was operated isocratically.Retention time was9min.Hydrogen peroxide was determined iodometrically for concen-trations greater than10À3mol dmÀ3.For concentra-tions of hydrogen peroxide lower than10À3mol dmÀ3, a modi®ed¯uorescence method15was used.In the water,ozone concentration was determined by the indigo method.16Ozone gas was analyzed with a GM19Anseros analyzer.In all the analytical tech-niques reproducibility was withinÆ5%.3RESULTS AND DISCUSSION3.1Experimental conditions and hypothesis of the kinetic modelTable3gives the experimental conditions applied to study the kinetic model of alachlor AOP through the use of ozone alone and combined with hydrogen peroxide in natural waters.As an example,Fig1presents the evolution of concentrations for alachlor,dissolved ozone and hydrogen peroxide in water leaving the reactor with time corresponding to one O3/H2O2 oxidation experiment.Notice that the steady state is reached in approximately25min at the experimental conditions applied.Other aspects related to the experi-mental results and the in¯uence of variables on the alachlor disappearance rate are given elsewhere.5,6 Once experiments were carried out,kinetic model-ling was performed by considering the following steps: .Determination of the residence time distribution function of gas and water phases through the reactor..Analysis of the kinetic regime of ozone absorption to establish the appropriate ozone absorption kinetics and propose the mechanism of reactions..Preparation of the mathematical model from the mass balance equations of the main species involved by considering the mechanism of reactions,rate data and RTDF information.Table2.Characteristics of surface waters used in this studySurface water pH COD(g mÀ3)A254TC/IC(g mÀ3) Cordobilla7.68.60.10120.6/4.1Gevora8.07.80.17224.2/6.1 Piedra Aguda8.27.30.19734.7/8.7 COD:chemical oxygen demand;TC:total carbon;IC:inorganic carbon; A254:absorbance at254nm UV radiation.Table3.Experimental conditions appliedSurface water Oxidizing system C1,0Â105(mol dmÀ3)m1,0Â105(mol minÀ1)R(g H2O2(g O3)À1)pH,in/outPiedra Aguda Ozone 3.3±4.47.0±7.4±13.78.1/7.5Gevora Ozone 3.5±4.4 5.9±6.2 3.5±7.0±9.7Buffered Cordobilla Ozone/hydrogen peroxide 4.5±4.89.7±10.20.31±0.58±1.16±1.858.1/7.7Gevora Ozone/hydrogen Peroxide 3.4±4.38.3±9.50.10±0.24±0.62±1.207.0BufferedGas¯ow rate20dm3hÀ1;20°C;t L=10min.FJ BeltraÂn et al3.2Residence time distribution function,RTDFFigure 2shows the RTDF,also called the E function,with time corresponding to the hydraulic residence times of 10min for the water phase and 7.5min for the gas phase.Also,theoretical E functions corresponding to the ideal situation of perfect mixing and plug ¯ow are plotted.Values of the the ®rst and second moments (mean residence time and variance)of the distribution functions 12were then calculated and are presented in Table 4.According to them,the number of equally sized continuous perfectly mixed tanks in series that simulate the actual ¯ow was determined:N1 21Also,the Peclet number was estimated through eqn (2)by a trial and error procedure:2 2PeÀ1À2Pe À1 1Àexp ÀPe À1 2As seen in Table 4,the water phase through the reactorpresented some partial dispersion as deduced from the Peclet number value (N =3.7,Pe L =6.3)while the gas phase of this reactor was close to perfect mixing (N ^1.6,Pe G =1.61).As a consequence of these results,for subsequent kinetic modelling purposes,the axial dispersion model has been taken to simulate the water phase and the gas phase has been considered to be perfectly mixed.3.3Kinetic regime of ozone absorption and mechanism of reactions of alachlor AOPOzone reacts in water through direct reactions with thecompounds present (alachlor in our case)and through free radicals,mainly hydroxyl radicals,that are formedfrom ozone decomposition.Ozone decomposition can be initiated or promoted in the presence of some substances or external agents like hydrogen peroxide or UV radiation,respectively.These reactions yield free radicals that eventually react with the compounds present in water.This is named the indirect reaction of ozone.17Once initiation reactions yield free radicals,a mechanism of reactions develop.Based on literature data a mechanism of reactions for the AOP of alachlor was proposed,as shown later.This mechanism contains direct reactions of ozone and hydroxyl radical with alachlor of known rate constants.1The mechan-ism is completed with a free radical set of reactions involving initiation,propagation and termination steps.Rate constants of these reactions have also been taken from the literature:7(i)Ozone±alachlor direct reaction:O 3 A À3Productsk D ;A 2:8dm 3mol À1s À13Figure 1.Evolution of concentrations of alachlor,dissolved ozone and formed hydrogen peroxide during the ozonation of alachlor with time in Cordobilla surface water.Conditions:20°C,gas flow rate 20dm 3h À1,C gH =8Â10À5mol dm À3;C 1,0=4.45Â10À5mol dm À3.Open symbols:experimental concentrations.Closed symbols:calculated concentrations at steady state at the reactoroutlet.Figure 2.Experimental and theoretical (for ideal flows)residence timedistribution function with time of (a)the water phase,and (b)the gas phase,in the reactor column used in this work.Conditions:V =2.5dm 3,t L =10min,t G =7.5min.Kinetic modelling of AOP alachlor removal from surface waterFree radical initiation reactions:O3 OHÀÀ3ÁHO2 ÁOÀ2k i1 70dm3molÀ1sÀ1 4O3 HOÀ2À3ÁHO2 ÁOÀ3k i2 2:8Â106dm3molÀ1sÀ1 5 O3 IÀ3I ÁOÀ3k1 6 where I represents the concentration of possible radical chain initiating species present in natural water.(iii)Free radical propagation reactions:ÁHO2À3ÁOÀ2 Hp K5 4:8 7 O3 ÁOÀ2À3O2 ÁOÀ3k p1 1:6Â109dm3molÀ1sÀ1 8 ÁOÀ3 H À3ÁHO3k p2 5Â1010dm3molÀ1sÀ1 9 ÁHO3À3ÁOH O2k p3 1:4Â105sÀ1 10 H2O2 ÁOHÀ3ÁHO2 H2Ok p4 2:7Â107dm3molÀ1sÀ1 11 HOÀ2 ÁOHÀ3ÁHO2 OHÀk p5 7:5Â109dm3molÀ1sÀ1 12 HCOÀ3 ÁOHÀ3ÁCOÀ3 H2Ok p6 2Â107dm3molÀ1sÀ1 13 CO2À3 ÁOHÀ3ÁCOÀ3 OHÀk p7 3:7Â108dm3molÀ1sÀ1 14 ÁCOÀ3 H2O2À3HCOÀ3 ÁHO2k p8 8Â105dm3molÀ1sÀ1 15 ÁCOÀ3 HOÀ2À3CO2À3 ÁHO2k p9 5:6Â107dm3molÀ1sÀ1 16A ÁOHÀ3ÁR Productsk OH;A 2:6Â1010dm3molÀ1sÀ1 17 ÁR O23ÁROO3ÁOÀ2 Pk p10 18Notice that reaction(18)considers the possible reaction of.R radicals with excess oxygen to yieldorganic peroxyl radicals that eventually can form the superoxide ion radical.Therefore,alachlor has been considered a promotor of ozone decom-position since by reacting with the hydroxyl radical(reaction(17)the superoxide ion radical is eventually regenerated(reaction(18).18 (iv)Free radical termination reactions:OM ÁOHÀ3Pk t1 5Â1010dm3molÀ1sÀ1 19 ÁCOÀ3 OMÀ3Pk t2 20 where OM stands for the organic matter content of the surface water in which alachlor is present.Notice that carbonate ion radicals,formed when hydroxyl radicals react with carbonate±bicarbonate ions(see reactions (13)and(14),also react with hydrogen peroxide (reactions(15)and(16)to regenerate the hydroper-oxide/superoxide ion radical19and with the organic matter present in water(reaction(20).20From the former reactions,carbonate ion radicals act as promotors of ozone decomposition while from the latter reaction they participate as scavengers or terminating agents of the chain mechanism.Due to the lack of rate data information concerning reaction (20)a parameter,w,representing the fraction of carbonate ion radicals that propagate the chain mech-anism was de®ned as follows:w 1Àk t2C OMk t2C OM k C C H2O2T21 where k c is:k Ck P8 k P910pHÀ11:81 10pHÀ11:822the value of11.8being the p K of hydrogen peroxide equilibrium.Since k t2is unknown,for kinetic model-ling calculations,a value of0.2as reported by Sunder and Hampel21was taken for w.In the proposed mechanism,the presence of hydrogen peroxide and carbonates implies the use of their corresponding acid±base equilibrium.In order to establish the kinetic model the kinetic regime of ozone reactions needs to be known.The kinetic regime of ozone reactions in water depends on the relative importance of chemical reaction and ozone mass transfer rates.These regimes are basically classi®ed as slow or fast and the dimensionless number of Hatta allows predictions of these kinetic possibi-lities.Since reactions of ozone with organic com-pounds in water usually follow second order kinetics, their corresponding Hatta number22is calculated asTable4.Non-idealflow dataWater phase¯ow Gas phase¯owt L(min)t m(min) 2 N Pe L t G(min)t m(min) 2 N Pe G 108.90.27 3.7 6.3 3.75 3.50.63 1.6 1.6FJ BeltraÂn et alfollows:HakD O 3C Mp k 2L23where k and k L are the rate constant of the ozone reaction and individual liquid phase mass transfer coef®cient,respectively,D O 3,the ozone diffusivity in water and C M the concentration of compound or chemical species reacting with ozone.At the condi-tions carried out in this work,second order reactions involving ozone (see mechanism above)produce Hatta numbers well below 0.3except for the case of concentrations of hydrogen peroxide higher than 0.01mol dm À3.This means that ozone reactions develop in the slow kinetic regime of absorption in the case of ozone alone and most of the ozone/hydrogen peroxide oxidation cases applied in this work.Thus,in most of the cases studied,ozone diffuses through the liquid ®lm close to the gas±water interphase and then it reaches the bulk water where it reacts.For the O 3/H 2O 2system at high peroxide concentration,reaction (5)develops in an intermedi-ate slow±moderate to fast kinetic regime of absorption (Ha >0.3),which means that part of the ozone also reacts while diffusing through the liquid layer.23In any case,for the O 3/H 2O 2reactions of environmental interest,concentrations of peroxide are low and the corresponding Hatta number remains lower than 0.3,the accepted limit between moderate and slow kinetic regimes.233.4Mathematical modelThe mathematical model was prepared from the mass balance equations of species present in water:ozone (both in the gas and water phases,alachlor,hydrogen peroxide and carbonate ions)and RTD information.Thus,from the RTD data some type of axial dispersion can be assumed to hold for the water phase ¯ow while the gas phase can be considered in perfect mixing.Accordingly,balance equations for the water phase follow the general equation:@C j D j @2C j 2Àu L @C jr j 24where r j refers to the kinetic law of compound j that expresses its rate of generation or removal through chemical reactions and,in addition,the mass transfer rate in the case of ozone.Reaction rate equations,r j ,can easily be deduced from the proposed mechanism.Notice that concentrations of hydroxyl,superoxide ion and carbonate ion radicals in reaction rate equations can be expressed as a function of concentration of molecular or stable species once the hypothesis of steady state is applied.7In the case of ozone,because of the slow reaction regime,ozonation is a two steps in series process constituted by diffusion of ozone through the ®lm layer and reactions in the bulk water.Accordingly,r j is de®ned as follows:r j N O 3 r O 3 k L a C *O 3ÀC O 3 r O 3k L a C gRTHeÀC O 3r O 3 25where r O 3represents the rate of ozone removal due to chemical reactions in water (see mechanism above)and N O 3the ozone absorption rate.For the gas phase,only the mass balance of ozone is considered (the rest of species are non-volatile).Since perfect mixing is assumed for the gas phase the mass balance of ozone in the gas phase through the reactor is as follows:1Àb V d C gd tQ G C gi ÀC g ÀbZH0N O 3S d h 26Equations (24),applied to any j species present in water,and (26)constitute the kinetic model of the alachlor AOP studied.At steady state (t >25min in Fig 1)and put in dimensionless form,both equations are as follows:1Pe L d 2 j d l 2Àd jd lj 0 27andgb t GZ10 O 3d l 1 28In eqn (27),the term x j varies depending on thechemical species considered.Thus,for ozone,this term is as follows:j t L o jgH O 3 29while for any other chemical species in water,x j is expressed as indicated below:j t Lo j C 1;030where C gH and C 1,0represent the concentrations of ozone in the gas and alachlor in water at the column inlet,respectively.Notice that subscripts 0and H represent conditions at the top and bottom of the column,respectively.Also,in eqns (29)and (30),o j is the dimensionless form of the chemical reaction rate of any j species in water while Z O 3,in eqn (29),represents the dimensionless form of the ozone absorption rate (see eqn (25)).The system of dimensionless second order differ-ential equations (eqn (27))was then reduced to the ®rst order differential equation system shown below by de®ning the following function:jd j d l31Kinetic modelling of AOP alachlor removal from surface waterWith eqn (31),eqn (27)remains as follows:1Pe L d jd lÀ j j 032Finally,from a trial and error procedure and the use of the fourth order Runge±Kutta method 24the system of dimensionless equations (eqns (31)and (32))was solved.The following initial conditions were applied:l 0 g supposed value 33 O 3 0d O 3=d l 034 Any other j speciesd j =d l 0Y j 135For c g ,the value corresponding to the experimental measurements at the column outlet (which corre-sponds to l =0)was ®rst assumed.Once the dimen-sionless pro®le of any j species in water,c j ,with the height of the reactor column was known,eqn (28)was used to con®rm the assumed value of c g .The kinetic model was solved at different conditions (ozone and hydrogen peroxide concentrations,type of natural water and pH).As an example,Fig 3depicts the evolution of calculated steady state concentrations of alachlor,hydrogen peroxide and ozone (in water and gas phases)with the height of the column.Also,Fig 3presents the experimental concentration of chemical species reached,at steady state conditions,at the column outlet (see open symbols).A compari-son between experimental and calculated concentra-tions can also be made from Fig 1.Figures 4and 5,on the other hand,present experimental and calculated data,at steady state conditions,on hydrogen peroxide concentration or conversion,X H 2O 2,H (in the caseofFigure 3.Kinetic modelling of the ozonation of alachlor in surface waters.Evolution of alachlor,hydrogen peroxide and dissolved ozone concentrations with the dimensionless height of reactor column.Conditions:20°C,gas flow rate 20dm 3h À1;C gH =8Â10À5mol dm À3;C 1,0=4.45Â10À5mol dm À3.Open symbols:experimental concentrations at the column outlet and at steady state.Closed symbols:calculated concentrations at steadystate.Figure 4.Kinetic modelling of alachlor ozonation in different surface waters.Experimental and calculated data at steady state.Experimental conditions:20°C,pH see Table 2,t L =10min,Q g =20dm 3dm À3.Surface water:Gevora:C gH =17.8Â10À4mol dm À3,C 1,0=3.58Â10À5mol dm À3;Cordobilla:C gH =20.9Â10À4mol dm À3,C 1,0=4.41Â10À5mol dm À3;Piedra Aguda:C gH =22.2Â10À4mol dm À3,C 1,0=3.32Â10À5mol dm À3.aX 1,H alachlor conversion at the reactor column outlet,(C 1,0ÀC 1,H )/C 1,0.bÉO 3,H ,dissolved ozone fraction at the reactor column outlet:C O 3,H /C gH .For the X axis,a represents C H 2O 2,H ,X 1,H or ÉO 3,H .Figure 5.Kinetic modelling of alachlor O 3/H 2O 2oxidation in different surface waters.Effect of the ozone/hydrogen peroxide feeding ratio on the steady state calculated and experimental data at the column outlet:For experimental conditions see Table 5.a X H 2O 2,H ,hydrogen peroxide conversion at the reactor column outlet,(C H 2O 2,0ÀC H 2O 2,H )/C H 2O 2,0.For the x axis,a represents C H 2O 2,H ,X 1,H or ÉO 3,H.FJ BeltraÂn et al。
Study_on_the_pharmacological_activities_and_chemic

ReviewStudy on the pharmacological activities and chemicalstructures of Viburnum dilatatumZhiheng Gao, Yufei Xi, Man Wang, Xiaoxiao Huang*, Shaojiang Song*Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research &Development, Liaoning Province, School of Traditional Chinese Materia Medica, ShenyangPharmaceutical University, Shenyang 110016, ChinaAbstractViburnum dilatatum (jiami in Chinese), belonging to the Caprifollaceae family, is widely distributed in Japan and China. Phytochemical investigations of Viburnum dilatatum (V. dilatatum) have resulted in the isolation of triterpenoids, phenolic glycosides essential oil, norisoprenoids, etc. Research results have shown that the chemical constituents of V. dilatatum possess various pharmacological activities, including antihyperglycemic, antioxidant activity and antiulcer effects. This study reviewed the chemical constituents and pharmacological activities of V. dilatatum to provide practical and useful information for further research and development of this plant.Keywords: Viburnum dilatatum; pharmacological activity; chemical structures1 IntroductionViburnum dilatatum (called jiami in Chinese, gamazumi in Japanese and snowball tree in English), beloinging to family Caprifoliaceae, is a deciduous low tree distributed widely in the hills of northern China and Japan [1]. There are many types of chemical constituents in Viburnum dilatatum (V. dilatatum), including triterpenoids, * Author to whom correspondence should be addressed. Address:School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Rd., Shenyang 110016, China; Tel.: +86-24-43520793 (Xiaoxiao Huang); +86-24-43520707 (ShaojiangSong);E-mail:*******************(XiaoxiaoHuang); ****************(ShaojiangSong).Received: 2021-04-16 Accepted: 2022-08-28phenolic glycosides and norisoprenoids [2-4]. The leaves have been utilized as a traditional Chinese medicine, and phenolic compounds have been reported as the main active chemical component of the leaves. Many researchers have analyzed the functions of these medicinal components and found that these components have good antioxidant antihyperglycemic and antiulcer effects. For example, the gamazumi crude extract obtained from the squeezed juice of the fruit prevented oxidative injury in rats [5]. This review described the chemical structures and pharmacological activities of V. dilatatum, so as to help readers understand comprehensively the research progress of V. dilatatum and provide help for the development of V. dilatatum.2 Chemical constituents and structuresPrevious reports have indicated that the main chemical constituents of V. dilatatum are phenolic glycosides and triterpenoids.2.1 Phenolic glycosidesThirteen phenolic glycosides were isolated and identified from V. dilatatum by extensive spectroscopic methods, namely p -hydroxyphenyl-6-O -trans-caffeoyl-β-D -glucoside (1) [6], p -hydroxyphenyl-6-O -trans-caffeoyl-β-D -alloside (2) [6], 4-allyl-2-methoxyphenyl-6-O -β-D -apiosyl(1→6)-β-D -glucoside (3) [6], 1-(4’-hydroxy-3’-methoxypheny1)-2-[2’’-hydroxy-4’’-(3’’’-hydroxypropyl)]-1,3-propanediol-l-O -β-D -glucopyranoside (erythro isomer) (4-7) [7], neochlorogenic acid methyl ester (8-9) [7], cryptochlorogenic acid methyl ester (10-11) [7], cyanidin-3-sambubioside (Cy-3-sam) (12) [8], cyanidin-3-glucoside (Cy-3-glc) (13) [8], 5-O -caffeoyl-4-methoxyl quinic acid (4-MeO-5-CQA) (14) [8], chlorogenic acid (5-CQA) (15) [8], quercetin (16) [8], 2-(glucopyranosyloxy)-benzyl-3-(glucopyranosyloxy)-benzoate (17) [9] and jiamizioside E (18) [10]. These structures are shown in Fig. 1.Fig. 1 Phenolic glycosides isolated from V . dilatatumContinued fig. 12.2 TriterpenoidsThere were about seventeen triterpenoids isolated and characterized from V. dilatatum , such as viburnols A (19) [11], viburnols B (20) [11], viburnols C (21) [11], viburnols D (22) [11], viburnols E (23) [11], viburnols F (24) [12], viburnols G (25) [12], viburnols H (26) [12], viburnols I (27) [12], viburnols J (28) [12],viburnols K (29) [12], viburnudienone B 2methyl ester (30) [13], viburnenone H 2 (31) [13],v i b u r n e n o n e B 2 m e t h y l e s t e r (32) [13], viburnudienone B 1 methyl ester (33) [13], viburnenone H 1 (34) [13], and viburnenone B 2 methyl ester (35) [13]. The structures are shown in Fig. 2.Continued fig. 23 Pharmacological activities3.1 Antioxidant activityOxidative stress caused by free radicals and their derivatives leads to disturbances in redox homeostasis. Reactive oxygen species (ROS) are not only endogenously produced during intracellular metabolic processes but also generated by exogenous stimuli such as UV radiation, pollutants, smoke and drugs. The cell triggers its defense systems or undergoes apoptosis when intracellular oxidative status increases. It influences numerous cellular processes including core signaling pathways, which are associated with development of systematic and chronic disorders, such as aging and cancer. Therefore, it is critical to remove cellular oxidants and restore redox balance.solution of V. dilatatum (GSS) had strong antioxidant activity in vivo and prevent stress-induced oxidative damage by the XYZ-dish method and the澳electron spin resonance (ESR) method [14]. The experimental result showed that the concentrations of lipid peroxide in plasma, liver and stomach in the GSS group were reduced. Furthermore, the activities of plasma lactic dehydrogenase, amylase and creatine phosphokinase are ordinarily increased by stress. However, these activities in the GSS group decreased to that in the control group. It was concluded that gastric ulcer formation, increase of lipid peroxidation in plasma and tissues and elevation of plasma enzymatic activities were confirmed in rats with water immersion restraint stress. It was also found that intake of GSS could protect the stomach and other tissues from oxidative damage.Kim et al. identified and isolated two major anthocyanins by NMR and LC-ESI-MS/MS, namely, cyanidin 3-sambubioside (I) and kuromanin (II) [15]. By the electron spin resonance method, the superoxide anion radical scavenging activities of I and II were evaluated with the IC 50 values of 17.3 and 69.6 µM, and their activities on hydroxyl radicals were evaluated with the IC 50 values of 4.3 and 53.2 mM. As the positive control, the IC 50 values of ascorbic acid were 74.2 µM on superoxide anion radicals and 3.0 mM on hydroxyl radicals, respectively. The above results suggested that these anthocyanins with radical scavenging properties might be the key compounds contributing to the antioxidant activity and physiological effects of V . dilatatum fruits.Woo et al. determined the free radical scavenging capacity of VD (the leaves of V. dilatatum ) [16]. Anti-oxidant activity of the extracts was assessed by the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) or 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals. Butylated hydroxytoluene (BHT), a synthetic antioxidant, or α-tocopherol, was used as the positive control in these assays. The experimental result showed that VD inducedincrease in radical scavenging activity. In addition, lipid peroxidation inhibitory activity was determined via measurement of MDA (Malondialdehyde) levels using mouse liver tissue homogenate treated with various concentrations of the extracts. The concentration-dependent decrease in MDA levels observed was consistent with radical scavenging activities of the extracts. To examine whether VD extracts could protect mam-malian cells from oxidative stress, cultures of a human mammary gland-derived epithelial cell line MCF-7 were treated with each extract prior to challenging them with tBHP. The intracellular ROS (Reactive oxygen species) production was determined with the relative intensity of dichlorofluorescein fluorescence. While intracellular ROS formation was significantly promoted by tBHP treatment, the augmented ROS level was significantly reduced after the treatment with VD extracts.3.2 Antihyperglycemic effectIwai et al. used an oral glucose tolerance test on the diabetic rats [17]. They found that the elevation of plasma glucose level after oral administration of 2 g/kg glucose was suppressed by the repeated administration of the freeze-dried powder of V. dilatatum fruit juice (CEV). The α-glucosidase inhibitory activities of isolated compounds from CEV were also measured. Cyanidin 3-sambubioside and 5-caffeoyl quinic acid A showed inhibitory activity. These results suggested that V. dilatatum fruit had the antihyperglycemic effects.4 ConclusionV. dilatatum is distributed widely in the hills of northern China and Japan. Currently, the studies on V. dilatatum have been conducted at home and abroad, but few studies focus on its chemical components and pharmacological activities. Previousphytochemical investigations showed that the constituents of V. dilatatum included triterpenoids, phenolic glycosides, norisoprenoids and other compounds. This study describes thirteen phenolic glycosides and seventeen triterpenoids and their different degrees of antihyperglycemic, antioxidant activity and antiulcer effects, aiming to provide a reference for further studies on V. dilatatum and pharmaceutical development.References[1] Jeffrey B, Harborne A. Colour atlas of medicinal plantsof Japan. Phytochemistry, 1981, 20: 1467.[2] Miyazawa M, Hashidume S, Takahashi T, et al. Aromaevaluation of gamazumi (Viburnum dilatatum) by aroma extract dilution analysis and odour activity value.Phytochem Anal, 2012, 23: 208-213.[3] Kurihara T, Kikuchi M. Studies on the constituentsof flowers. IV. On the components of the flower of Viburnum dilatatum Thunb. J Health Sci, 1975, 95: 1098-1102.[4] Machida K, Kikuchi M. Norisoprenoids from Viburnumdilatatum. Phytochemistry, 1996, 41: 1333-1336. [5] Iwai K, Onodera A, Matsue H. Mechanism of preventiveaction of Viburnum dilatatum Thunb (gamazumi) crude extract on oxidative damage in rats subjected to stress. J Sci Food Agric, 2010, 83: 1593-1599.[6] Machida K, Nakano Y, Kikuchi M. Phenolic glycosidesfrom Viburnum dilatatum. Phytochemistry, 1991, 30: 2013-2014.[7] Machida K, Kikuchi M. Phenolic compounds fromViburnum dilatatum. Phytochemistry, 1992, 31: 3654-3656.[8] Kim MY, Iwai K, Matsue H. Phenolic compositions ofViburnum dilatatum Thunb. fruits and their antiradical properties. J Food Compos Anal, 2005, 18: 789-802. [9] Lu D, Yao S. Phenolic glycoside from the roots ofViburnum dilatatum. Nat Prod Commun, 2009, 4: 945-946.[10] Wu B, Zeng X, Zhang Y. New metabolite fromViburnum dilatatum. Nat Prod Commun, 2010, 5: 1097-1098.[11] Machida K, Kikuchi M. Viburnols: Novel triterpenoidswith a rearranged dammarane skeleton from Viburnum dilatatum. Tetrahedron Lett, 1996, 37: 4157-4160. [12] Machida K, Kikuchi M. Viburnols: Six noveltriterpenoids from Viburnum dilatatum. Tetrahedron Lett, 1997, 38: 571-574.[13] Machida K, Kikuchi M. Studies on the Constituents ofViburnum Species. XIX. Six New Triterpenoids from Viburnum dilatatum Thunb. Chem Pharm Bull, 1999, 47: 692-694.[14] Iwai K, Onodera A, Matsue H, et al. Antioxidant activityand inhibitory effect of Gamazumi (Viburnum dilatatum THUNB.) on oxidative damage induced by water immersion restraint stress in rats. Int J. Food Sci Nutr, 2001, 52: 443-451.[15] Kim MY, Iwai K, Onodera A, et al. Identification andAntiradical Properties of Anthocyanins in Fruits of Viburnum dilatatum Thunb. J Agric Food Chem, 2003, 51: 6173-6177.[16] Woo YJ, Lee HJ, Jeong YS, et al. Antioxidant Potentialof Selected Korean Edible Plant Extracts. Bio Med Res Int, 2017, 2017: 1-9.[17] Iwai K, Kim MY, Akio O, et al. Alpha-glucosidaseinhibitory and antihyperglycemic effects of polyphenols in the fruit of Viburnum dilatatum Thunb. J Agric Food Chem, 2006, 54: 4588-4592.。
香精油中农药残留

Determination of Pesticide Minimum Residue Limits in Essential OilsReport No 3A report for the Rural Industries Research andDevelopment CorporationBy Professor R. C. Menary & Ms S. M. GarlandJune 2004RIRDC Publication No 04/023RIRDC Project No UT-23A© 2004 Rural Industries Research and Development Corporation.All rights reserved.ISBN 0642 58733 7ISSN 1440-6845‘Determination of pesticide minimum residue limits in essential oils’, Report No 3Publication No 04/023Project no.UT-23AThe views expressed and the conclusions reached in this publication are those of the author and not necessarily those of persons consulted. RIRDC shall not be responsible in any way whatsoever to any person who relies in whole or in part on the contents of this report.This publication is copyright. However, RIRDC encourages wide dissemination of its research, providing the Corporation is clearly acknowledged. For any other enquiries concerning reproduction, contact the Publications Manager on phone 02 6272 3186.Researcher Contact DetailsProfessor R. C. Menary & Ms S. M. GarlandSchool of Agricultural ScienceUniversity of TasmaniaGPO Box 252-54HobartTasmania 7001AustraliaPhone: (03) 6226 2723Fax: (03) 6226 7609Email: r.menary@.auIn submitting this report, the researcher has agreed to RIRDC publishing this material in its edited form.RIRDC Contact DetailsRural Industries Research and Development CorporationLevel 1, AMA House42 Macquarie StreetBARTON ACT 2600PO Box 4776KINGSTON ACT 2604Phone: 02 6272 4819Fax: 02 6272 5877Email: rirdc@.auWebsite: .auPublished in June 2004Printed on environmentally friendly paper by Canprint.FOREWORDInternational regulatory authorities are standardising the levels of pesticide residues present in products on the world market which are considered acceptable. The analytical methods to be used to confirm residue levels are also being standardised. To constructively participate in these processes, Australia must have a research base capable of constructively contributing to the establishment of methodologies and must be in a position to assess the levels of contamination within our own products.Methods for the analysis for pesticide residues rarely deal with their detection in the matrix of essential oils. This project is designed to develop and validate analytical methods and apply that methodology to monitor pesticide levels in oils produced from commercial harvests. This will provide an overview of the levels of pesticide residues we can expect in our produce when normal pesticide management programs are adhered to.The proposal to produce a manual which deals with the specific problems associated with detection of pesticide residues in essential oils is intended to benefit the essential oil industry throughout Australia and may prove useful to other horticultural products.This report is the third in a series of four project reports presented to RIRDC on this subject. It is accompanied by a technical manual detailing methodologies appropriate to the analysis for pesticide residues in essential oils.This project was part funded from RIRDC Core Funds which are provided by the Australian Government. Funding was also provided by Essential Oils of Tasmania and Natural Plant Extracts Cooperative Society Ltd.This report, an addition to RIRDC’s diverse range of over 1000 research publications, forms part of our Essential Oils and Plant Extracts R&D program, which aims for an Australian essential oils and plant extracts industry that has established international leadership in production, value adding and marketing.Most of our publications are available for viewing, downloading or purchasing online through our website:•downloads at .au/fullreports/index.html•purchases at .au/eshopSimon HearnManaging DirectorRural Industries Research and Development CorporationAcknowledgementsOur gratitude and recognition is extended to Dr. Noel Davies (Central Science Laboratories, University of Tasmania) who provided considerable expertise in establishing procedures for chromatography mass spectrometry.The contribution to extraction methodologies and experimental work-up of Mr Garth Oliver, Research Assistant, cannot be underestimated and we gratefully acknowledge his enthusiasm and novel approaches.Financial and ‘in kind’ support was provided by Essential Oils Industry of Tasmania, (EOT).AbbreviationsADI Average Daily IntakeAGAL Australian Government Analytical Laboratoriesingredientai activeAPCI Atmospheric Pressure Chemical IonisationBAP Best Agricultural PracticesenergyCE collisionDETA DiethylenetriamineECD Electron Capture DetectorionisationESI ElectrosprayFPD Flame Photometric DetectionChromatographyGC GasResolutionHR HighChromatographyLC LiquidLC MSMS Liquid Chromatography with detection monitoring the fragments of Mass Selected ionsMRL Maximum Residue LimitSpectrometryMS MassNRA National Registration AuthorityR.S.D. Relative Standard DeviationSFE Supercritical Fluid ExtractionSIM Single Ion MonitoringSPE Solid Phase ExtractionTIC Total Ion ChromatogramContents FOREWORD (III)ACKNOWLEDGEMENTS (IV)ABBREVIATIONS (V)CONTENTS (VI)EXECUTIVE SUMMARY (VII)1. INTRODUCTION (1)1.1B ACKGROUND TO THE P ROJECT (1)1.2O BJECTIVES (2)1.3M ETHODOLOGY (2)2. EXPERIMENTAL PROTOCOLS & DETAILED RESULTS (3)2.1M ETHOD D EVELOPMENT (3)2.2M ONITORING OF H ARVESTS (42)2.3P RODUCTION OF M ANUAL (46)3. CONCLUSIONS (47)IMPLICATIONS & RECOMMENDATIONS (50)BIBLIOGRAPHY (50)Executive SummaryThe main objective of this project was to continue method development for the detection of pesticide residues in essential oils, to apply those methodologies to screen oils produced by major growers in the industry and to produce a manual to consolidate and coordinate the results of the research. Method development focussed on the effectiveness of clean-up techniques, validation of existing techniques, the assessment of the application of gas chromatography (GC) with detection using electron capture detectors (ECD), flame photometric detectors (FPD) and high pressure liquid chromatography (HPLC) with ion trap mass selective (MS) detection.The capacity of disposable C18 cartridges to separate components of boronia oil was found to be limited with the majority of boronia components being eluted on the solvent front, with little to no separation achieved. The cartridges were useful, however, in establishing the likely interaction of reverse phases (RP) C18 columns with components of essential oils, using polar mobile phases . The loading of large amounts of oil onto RP HPLC columns presents the risk of permanently contaminating the bonded phases. The lack of retention of components on disposable SPE C18 cartridges, despite the highly polar mobile phase, presented a good indication that essential oils would not accumulate on HPLC RP columns.The removal of non-polar essential oil components by solvent partitioning of distilled oils was minimal, with the recovery of pesticides equivalent to that recorded for the essential oil components. However application of this technique was of advantage in the analysis of solvent extracted essential oils such as those produced from boronia and blackcurrant.ECD was found to be successful in the detection of terbacil, bromacil, haloxyfop ester, propiconazole, tebuconazole and difenaconzole. However, analysis of pesticide residues in essential oils by application of GC ECD is not sufficiently sensitive to allow for a definitive identification of any contaminant. As a screen, ECD will only be effective in establishing that, in the absence of a peak eluting with the correct retention time, no gross contamination of pesticide residues in an essential oil has occurred . In the situation where a peak is recorded with the correct elution characteristics, and which is enhanced when the sample is fortified with the target analyte, a second means of contaminant identification would be required. ECD, then, can only be used to rule out significant contamination and could not in itself be adequate for a positive identification of pesticide contamination.Benchtop GC daughter, daughter mass spectrometry (MSMS) was assessed and was not considered practical for the detection of pesticide residues within the matrix of essential oils without comprehensive clean-up methodologies. The elution of all components into the mass spectrometer would quickly lead to detector contamination.Method validation for the detection of 6 common pesticides in boronia oil using GC high resolution mass spectrometry was completed. An analytical technique for the detection of monocrotophos in essential oils was developed using LC with detection by MSMS. The methodology included an aqueous extraction step which removed many essential oil components from the sample.Further method development of LC MSMS included the assessment of electrospray ionisation (ESI) and atmospheric pressure chemical ionisation (APCI. For the chemicals trialed, ESI has limited application. No response was recorded for some of the most commonly used pesticides in the essential oil industry, such as linuron, oxyflurofen, and bromacil. Overall, there was very little difference between the sensitivity for ESI and APCI. However, APCI was slightly more sensitive for the commonly used pesticides, tebuconazole and propiconazole, and showed a response, though poor, to linuron and oxyflurofen. In addition, APCI was the preferred ionisation method for the following reasons,♦APCI uses less nitrogen gas compared to ESI, making overnight runs less costly;♦APCI does not have the high back pressure associated with ionisation by ESI such that APCI can be run in conjunction with UV-VIS without risk of fracturing the cell, which is pressure sensitive. Analytes that ionised in the negative APCI mode were incorporated into a separate screen which included bromacil, terbacil, and the esters of the fluazifop and haloxyfop acids. Further work using APCI in the positive mode formed the basis for the inclusion of monocrotophos, pirimicarb, propazine and difenaconazole into the standard screen already established. Acephate, carbaryl, dimethoate, ethofumesate and pendimethalin all required further work for enhanced ionisation and / or improved elution profiles. Negative ionisation mode for APCI gave improved characteristics for dicamba, procymidone, MCPA and mecoprop.The thirteen pesticides included in this general screen were monocrotophos, simazine, cyanazine, pirimicarb, propazine, sethoxydim, prometryb, tebuconazole, propiconazole, , difenoconazole and the esters of fluroxypyr, fluazifop and haloxyfop.. Bromacil and terbacil were not included as both require negative ionisation and elute within the same time window as simazine, which requires positive ionisation. Cycling the MS between the two modes was not practical.The method validation was tested against three oils, peppermint, parsley and fennel.Detection limits ranged from 0.1 to 0.5 mgkg-1 within the matrix of the essential oils, with a linear relationship established between pesticide concentration and peak height (r2 greater than 0.997) and repeatabilities, as described by the relative standard deviation (r.s.d), ranging from 3 to 19%. The type of oil analysed had minimal effect on the response function as expressed by slope of the standard curve.The pesticides which have an carboxylic acid moiety such as fluazifop, haloxyfop and fluroxypyr, present several complications in any analytical method development. The commercial preparations usually have the carboxylic acid in the ester form, which is hydrolysed to the active acidic form on contact with soil and vegetation. In addition, the esters may be present in several forms, such as the ethoxy ethyl or butyl esters. Detection using ESI was tested. Preliminary results indicate that ESI is unsuitable for haloxyfop and fluroxypyr ester. Fluazifop possessed good ionisation characteristics using ESI, with responses approximately thirty times that recorded for haxloyfop. Poor chromatography and response necessitated improved mobile phase and the effect of pH on elution characteristics was considered the most critical parameter. The inclusion of acetic acid improved peak resolution.The LC MSMS method for the detection of dicamba, fluroxypyr, MCPA, mecoprop and haloxyfop in peppermint and fennel distilled oils underwent the validation process. Detection limits ranged from 0.01 to 0.1 mgkg-1Extraction protocols and LC MSMS methods for the detection of paraquat and diquat were developed. ESI produced excellent responses for both paraquat and diquat, after some modifications of the mobile phase. Extraction methodology using aqueous phases were developed. Extraction with carbonate buffer proved to be the most effective in terms of recovery and robustness. A total ion chromatogram of the LC run of an aqueous extract of essential oil was recorded and detection using a photodiode array detector confirmed that very little essential oil matrix was co-extracted. The low background noise indicated that samples could be introduced directly into the MS. This presented a most efficient and rapid way for analysis of paraquat and diquat, avoiding the need for specialised columns or modifiers to be included in the mobile phase to instigate ion exchange.The adsorbtion of paraquat and diquat onto glass and other surfaces was reduced by the inclusion of diethylenetriamine (DETA). DETA preferentially accumulates on the surfaces of sample containers, competitively binding to the adsorption sites. All glassware used in the paraquat diquat analysis were washed in a 5% solution of 0.1M DETA, DETA was included in all standard curve preparations, oils were extracted with aqueous DETA and the mobile phase was changed to 50:50 DETA / methanol. The stainless steel tubing on the switching valve was replaced with teflon, further improvingreproducibility. Method validation was undertaken of the analysis of paraquat and diquat using the protocols established. The relationship between analyte concentration and peak area was not linear at low concentrations, with adsorption more pronounced for paraquat, such that the response for this analyte was half that seen for diquat and the 0.1 mgkg-1 level.The development of a method for the detection of the dithiocarbamate, mancozeb was commenced. Disodium N, N'-ethylenebis(dithiocarbamate) was synthesised as a standard for the derivatised final analytical product. An LC method, with detection using MSMS, was successfully completed. The inclusion of a phase transfer reagent, tetrabutylammonium hyrdrogen sulfate, required in the derivatisation step, contaminated the LC MSMS system, such that any signal from the target analyte was masked. Alternatives to the phase transfer reagent are now being investigated.Monitoring of harvests were undertaken for the years spanning 1998 to 2001. Screens were conducted covering a range of solvent extracted and distilled oils. Residues tested for included tebuconazole, simazine, terbacil, bromacil, sethoxydim, prometryn, oxyflurofen, pirimicarb, difenaconazole, the herbicides with acidic moieties and paraquat and diquat. Problems continued for residues of propiconazole in boronia in the 1998 / 1999 year with levels to 1 mgkg-1 still being detected. Prometryn residues were detected in a large number of samples of parsley oil.Finally the information gleaned over years of research was collated into a manual designed to allow intending analysts to determine methodologies and equipment most suited to the type of the pesticide of interest and the applicability of analytical equipment generally available.1. Introduction1.1 Background to the ProjectResearch undertaken by the Horticultural Research Group at the University of Tasmania, into pesticide residues in essential oils has been ongoing for several years and has dealt with the problems specific to the analysis of residues within the matrix of essential oils. Analytical methods for pesticides have been developed exploiting the high degree of specificity and selectivity afforded by high resolution gas chromatography mass spectrometry. Standard curves, reproducibility and detection limits were established for each. Chemicals, otherwise not amenable to gas chromatography, were derivatised and incorporated into a separate screen to cover pesticides with acidic moieties.Research has been conducted into low resolution GC mass selective detectors (MSD and GC ECD. Low resolution GC MSD achieved detection to levels of 1 mgkg-1 in boronia oil, whilst analysis using GC ECD require a clean-up step to effectively detect halogenated chemicals below 1mgkg-1.Dithane (mancozeb) residues were digested using acidified stannous chloride and the carbon disulphide generated from this reaction analysed by GC coupled to FPD in the sulphur mode.Field trials in peppermint crops were established in accordance with the guidelines published by the National Registration Authority (NRA), monitoring the dissipation of Tilt and Folicur residues in peppermint leaves and the co-distillation of these residues with hydro-distilled peppermint oils were assessed.Development of extraction protocols, analytical methods, harvest monitoring and field trials were continued and were detailed in a subsequent report. Solvent-based extractions and supercritical fluid extraction (SFE) was found to have limited application in the clean-up of essential oilsIn conjunction with Essential Oils of Tasmania (EOT), the contamination risk, associated with the introduction of a range of herbicides, was assessed through a series of field trials. This required analytical method development to detect residues in boronia flowers, leaf and oil. The methodology for a further nine pesticides was successful applied. Detection limits for these chemicals ranged from 0.002 mgkg-1 to 0.1 mgkg-1. In addition, methods were developed to analyse for herbicides with active ingredients (ai) whose structure contained acidic functional groups. Two methods of pesticide application were trialed. Directed sprays refer to those directed on the stems and leaves of weeds at the base of boronia trees throughout the trial plot. Cover sprays were applied over the entire canopy. For all herbicides for which significant residues were detected, it was evident that cover sprays resulted in contamination levels ten times those occurring as a result of directed spraying in some instances. Chloropropham, terbacil and simazine presented potentially serious residue problems, with translocation of the chemical from vegetative material to the flower clearly evident.Directed spray applications of diuron and dimethenamid presented only low residue levels in extracted flowers with adequate control of weeds. Oxyflurofen and the mixture of bromacil and diuron (Krovar) presented only low levels of residues when used as a directed spray and were effective as both post and pre-emergent herbicides. Only very low levels of residues of both sethoxydim and norflurazon were detected in boronia oil produced in crops treated with directed spray applications. Sethoxydim was effective as a cover spray for grasses whilst norflurazon showed potential as herbicide to be used in combination with other chemicals such as diuron, paraquat and diquat. Little contamination of boronia oils by herbicides with acidic moieties was found. This advantage, however, appears to be offset by the relatively poor weed control. Both pendimethalin and haloxyfop showed good weed control. Both, however, present problems with chemical residues in boronia oil and should only be used as a directed sprayThe stability of tebuconazole, monocrotophos and propiconazole in boronia under standard storage conditions was investigated. Field trials of tebuconazole and propiconazole were established in commercial boronia crops and the dissipation of both were monitored over time. The amount of pesticide detected in the oils was related to that originally present in the flowers from which the oils were produced.Experiments were conducted to determine whether the accumulation of terbacil residues in peppermint was retarding plant vigour. The level recorded in the peppermint leaves were comparatively low. Itis unlikely that terbacil carry over is the cause for the lack of vigour in young peppermint plants.Boronia oils produced in 1996, 1997 and 1998 were screened for pesticides using the analytical methods developed. High levels of residues of propiconazole were shown to persist in crops harvested up until 1998. Field trials have shown that propiconazole residues should not present problems if the fungicide is used as recommended by the manufacturers.1.2 Objectives♦Provide the industry, including the Standards Association of Australia Committee CH21, with a concise practical reference, immediately relevant to the Australian essential oil industry♦Facilitate the transfer of technology from a research base to practical application in routine monitoring programs♦Continue the development of analytical methods for the detection of metabolites of the active ingredients of pesticide in essential oils.♦Validate the methods developed.♦Provide industry with data supporting assurances of quality for all exported products.♦Provide a benchmark from which Australia may negotiate the setting of a realistic maximum residue limit (MRL)♦Determine whether the rate of uptake is relative to the concentration of active ingredient on the leaf surface may establish the minimum application rates for effective pest control.1.3 MethodologyThree approaches were used to achieve the objectives set out above.♦Continue the development and validation of analytical methods for the detection of pesticide residues in essential oils. Analytical methods were developed using gas chromatography high resolution mass spectrometry (GC HR MS), GC ECD, GC FPD and high pressure liquid chromatography with detection using MSMS.♦Provide industry with data supporting assurances of quality for all exported products.♦Coordinate research results into a comprehensive manual outlining practical approaches to the development of analytical proceduresOne aspect of the commissioning of this project was to provide a cost effective analytical resource to assess the degree of the pesticide contamination already occurring in the essential oils industry using standard pesticide regimens. Oil samples from annual harvests were analysed for the presence of pesticide residues. Data from preceding years were collated to determine the progress or otherwise, in the application of best agricultural practice (BAP).2. Experimental Protocols & Detailed ResultsThe experimental conditions and results are presented under the following headings:♦Method Development♦Monitoring of Commercial Harvests♦Production of a Manual2.1 Method DevelopmentMethod development focussed on the effectiveness of clean-up techniques, validation of existing techniques, the assessment of the application of GC ECD and FPD and high pressure liquid chromatography with ion trap MS, MS detection.2.1.1 Clean-up Methodologies2.1.1.i. Application of Disposable SPE cartridges in the clean-up of pesticide residues in essentialoilsLiterature reviews provided limited information with regards to the separation of contaminants within essential oils. The retention characteristics of disposable C18 cartridges were trialed.Experiment 1;Aim : To assess the capacity of disposable C18 cartridges to the separation of boronia oil components. Experimental : Boronia concrete (49.8 mg) was dissolved in 0.5 mL of acetone and 0.4 mL of chloroform was added. 1mg of octadecane was added as an internal standard. A C18 Sep-Pak Classic cartridge (short body) was pre- conditioned with 1.25 mL of methanol, which was passed through the column at 7.5 mLmin-1, followed by 1.25 mL of acetone, at the same flow rate. The boronia samplewas then applied to the column at 2 mLmin-1 flow and eluted with 1.25 mL of acetone / chloroform (5/ 4) and then eluted with a further 2.5 mL of chloroform. 5 fractions of 25 drops each were collected. The fractions were analysed by GC FID using the following parametersAnalytical parameters6890PackardHewlettGCcolumn: Hewlett Packard 5MS 30m, i.d 0.32µmcarrier gas instrument grade nitrogeninjection volume: 1µL (split)injector temp: 250°Cdetector temp: 280°Cinital temp: 50°C (3 min), 10°Cmin-1 to 270°C (7 mins)head pressure : 10psi.Results : Table 1 record the percentage volatiles detected in the fractions collectedFraction 1 2 3 4 5 % components eluting 18 67 13 2636%monoterpenes 15%sesquiquiterpenes 33 65 2%high M.W components 1 43 47 9Table 1. Percentage volatiles eluting from SPE C18 cartridgesDiscussion : The majority of boronia components eluted on the solvent front, effecting minimal separation. This area of SPE clean-up of essential oils requires a wide ranging investigation, varying parameters such as cartridge type and polarity of mobile phase.Experiment 2.Aim : For the development of methods using LC MSMS without clean-up steps, the potential for oil components to accumulate on the reverse phase (RP) column must be assessed. The retention of essential oil components on SPE C18 cartridges, using the same mobile phase as that to be used in theLC system, would provide a good indication as to the risk of contamination of the LC columns withoil components.Experimental: Parsley oil (20-30 mg) was weighed into a GC vial. 200 µL of a 10 µgmL-1 solution (equivalent to 100mgkg-1 in oil) of each of sethoxydim, simazine, terbacil, prometryn, tebuconazoleand propiconazole were used to spike the oil, which was then dissolved in 1.0 mL of acetonitrile. The solution was then slowly introduced to the C18 cartridge (Waters Sep Pac 'classic' C18 #51910) using a disposable luer lock, 10 mL syringe, under constant manual pressure, and eluted with 9 mLs of acetonitrile. Ten, 1 mL fractions were collected and transferred to GC vials. 1mg of octadecane was added to each vial and the samples were analysed by GC FID under the conditions described in experiment 1.The experiment was repeated using C18 cartridges which had been pre-conditioned with distilled waterfor 15 mins. Again, parsley oil, spiked with pesticides was eluted with acetonitrile and 5 x 1 mL fractions collected.Results: The majority of oil components and pesticides were eluted from the C18 cartridge in the firsttwo fractions. Little to no separation of the target pesticides from the oil matrix was achieved. Table2 lists the distribution of essential oil components in the fractions collected.Fraction 1 2 3 4 5 % components eluting 18 67 13 2663%monoterpenes 15%sesquiquiterpenes 33 65 2%high M.W components 1 43 47 9water conditioned% components eluting 35 56 8 12%monoterpenes 3068%sesquiquiterpenes 60 39 1 0%high M.W components 0 50 42 7Table 2. Percentage volatiles eluting for SPE C18 cartridgesFigure 1 shows a histogram of the percentage distribution of components from the oil in each of the four fractions.Figure 1. Histogram of the percentage of volatiles of distilled oils in each of four fraction elutedon SPE C18 cartridges (non-preconditioned)Figure 2. Histogram of the percentage of volatiles of distilled oils in each of four fraction elutedon SPE C18 cartridges (preconditioned)Discussion : The chemical properties of many of the target pesticides, including polarity, solubility in organic solvents and chromatographic behaviour, are similar to the majority of essential oil components. This precludes the effective separation of analytes from such matrices through the use of standard techniques, where the major focus is pre-concentration of pesticide residues from water or water based vegetative material. However, this experiment served to provide a good indication that under HPLC conditions, where a reverse phase C18 column is used in conjunction with acetonitrile / water based mobile phases, essential oil components do not remain on the column.。
全国大学英语CET四级考试试卷及答案指导(2025年)

2025年全国大学英语CET四级考试模拟试卷及答案指导一、写作(15分)CET-4 Writing SectionDirections: For this part, you are allowed 30 minutes to write a short essay entitled “The Importance of Teamwork”. You should write at least 120 words but no more than 180 words.Sample Essay: The Importance of TeamworkIn today’s fast-paced and highly competitive world, the concept of teamwork has become more crucial than ever. It is often said that one can go fast alone, but to go far, one must go together. This saying underlines the importance of teamwork in achieving common goals effectively and efficiently.Teamwork allows for the pooling of diverse skills and talents, which leads to more innovative solutions and better decision-making. When individuals with different backgrounds and expertise collaborate, they bring unique perspectives to the table, fostering an environment where creativity thrives. Furthermore, working as a team builds a support system, enabling members to rely on each other during challenging times, thus reducing stress and increasing job satisfaction.Another significant benefit of teamwork is the ability to accomplish tasksthat would be impossible for an individual to handle. By dividing work among team members based on their strengths, teams can tackle complex projects, ensuring all aspects are thoroughly covered. This not only improves the quality of work but also accelerizes the completion time.In conclusion, the value of teamwork cannot be overstated. It is through collaboration and mutual support that we can achieve great things, overcome obstacles, and reach our full potential. Embracing the spirit of teamwork is essential for both personal and professional success in our interconnected world.Analysis:•Introduction: The essay begins with a clear statement about the increasing significance of teamwork in the modern era, setting up the main argument.•Body Paragraphs:•The first body paragraph discusses how teamwork enhances innovation and decision-making by combining varied skills and viewpoints.•The second body paragraph highlights the supportive nature of teamwork, emphasizing its role in managing stress and boosting morale.• A third point is made about the efficiency and effectiveness gained from dividing labor according to individual strengths, allowing for thesuccessful execution of complex tasks.•Conclusion: The concluding paragraph reinforces the thesis, summarizing the key benefits of teamwork and linking them to broader concepts ofachievement and personal growth.This sample response adheres to the word limit (156 words), maintains a coherent structure, and provides specific examples to support the main points, making it a strong example for the CET-4 writing section.二、听力理解-短篇新闻(选择题,共7分)第一题News Item 1:A new study has found that the popularity of online shopping has led to a significant increase in the use of plastic packaging. The researchers analyzed data from various e-commerce platforms and discovered that the amount of plastic packaging used in online orders has doubled over the past five years. This has raised concerns about the environmental impact of e-commerce and the need for more sustainable packaging solutions.Questions:1、What is the main issue addressed in the news?A) The decline of traditional shopping methods.B) The environmental impact of online shopping.C) The growth of e-commerce platforms.D) The advantages of plastic packaging.2、According to the news, what has happened to the use of plastic packaging in online orders over the past five years?A) It has decreased by 50%.B) It has remained stable.C) It has increased by 25%.D) It has doubled.3、What is the primary concern raised by the study regarding online shopping?A) The increase in the number of e-commerce platforms.B) The high cost of online shopping.C) The environmental impact of plastic packaging.D) The difficulty in returning products.Answers:1、B) The environmental impact of online shopping.2、D) It has doubled.3、C) The environmental impact of plastic packaging.第二题Section B: Short NewsIn this section, you will hear one short news report. At the end of the news report, you will hear three questions. After each question, there is a pause. During the pause, you must read the four choices marked A), B), C) and D), and decide which is the best answer. Then mark the corresponding letter on the Answer Sheet with a single line through the center.News Report:The World Health Organization announced today that it has added the ChineseSinovac COVID-19 vaccine to its list of vaccines approved for emergency use. This move will facilitate the distribution of the vaccine in lower-income countries participating in the COVAX initiative aimed at ensuring equitable access to vaccines globally. The WHO praised the Sinovac vaccine for its easy storage requirements, making it ideal for areas with less sophisticated medical infrastructure.Questions:1、According to the news report, what did the WHO announce?A)The end of the pandemicB)Approval of a new vaccineC)Launch of a global health campaignD)Increased funding for vaccine researchAnswer: B) Approval of a new vaccine2、What was highlighted about the Sinovac vaccine by the WHO?A)It is the most effective vaccine availableB)It requires simple storage conditionsC)It is cheaper than other vaccinesD)It has no side effectsAnswer: B) It requires simple storage conditions3、What is the purpose of the COVAX initiative mentioned in the report?A)To speed up vaccine developmentB)To provide financial support to vaccine manufacturersC)To ensure equal access to vaccines worldwideD)To promote travel between countriesAnswer: C) To ensure equal access to vaccines worldwide三、听力理解-长对话(选择题,共8分)第一题Part Three: Long ConversationsIn this section, you will hear 1 long conversation. The conversation will be played twice. After you hear a part of the conversation, there will be a pause. Both the questions and the conversation will be spoken only once. After you hear a question, you must choose the best answer from the four choices marked A), B), C), and D). Then mark the corresponding letter on Answer Sheet 2 with a single line through the center.Now, listen to the conversation.Conversational Excerpt:M: Hey, Jane, how was your day at the office today?W: Oh, it was quite a challenge. I had to deal with a lot of issues. But I think I handled them pretty well.M: That’s good to hear. What were the main issues you faced?W: Well, first, we had a problem with the new software we’re tryin g to implement. It seems to be causing some technical difficulties.M: Oh no, that sounds frustrating. Did you manage to fix it?W: Not yet. I’m still trying to figure out what’s wrong. But I’m workingon it.M: That’s important. The company can’t afford a ny downtime with this software.W: Exactly. And then, I had to deal with a customer complaint. The customer was really upset because of a delayed shipment.M: That’s never a good situation. How did you handle it?W: I tried to be understanding and offered a discount on their next order. It seemed to calm them down a bit.M: That was a good move. Did it resolve the issue?W: Yes, it did. They’re satisfied now, and I think we’ve avoided a bigger problem.M: It sounds like you had a busy day. But you did a good job handling everything.W: Thanks, I’m glad you think so.Questions:1、What was the main issue the woman faced with the new software?A) It was causing problems with the computer systems.B) It was taking longer to install than expected.C) It was causing technical difficulties.D) It was not compatible with their existing systems.2、How did the woman deal with the customer complaint?A) She escalated the issue to her supervisor.B) She offered a discount on the customer’s next order.C) She apologized directly to the customer.D) She sent the customer a refund check.3、What was the woman’s impression of her day at work?A) It was uneventful and unchallenging.B) It was quite stressful but rewarding.C) It was a day filled with unnecessary meetings.D) It was a day where she didn’t accomplish much.4、What did the man say about the woman’s day at work?A) He thought it was unproductive.B) He felt she had handled everything well.C) He thought she should have asked for help.D) He believed she should take a break.Answers:1、C2、B3、B4、B第二题对话内容:Man:Hey, Sarah. I heard you’re planning to go on a trip next month. Where are you heading?Sarah:Oh, hi, Mike! Yes, I’m really excited about it. I’m going to Japan. It’s my first time there.Man:That sounds amazing! How long will you be staying? And what places are you planning to visit?Sarah:I’ll be there for two weeks. My plan is to start in Tokyo and then travel to Kyoto, Osaka, and Hiroshima. I’ve always been fascinated by the mix of traditional and modern culture in Japan.Man: Two weeks should give you plenty of time to see a lot. Are you going alone or with someone?Sarah:Actually, I’m going with a group of friends from college. We all decided to take this trip together after graduation. It’ll be great to experience it with them.Man:That’s wonderful! Do you have everything planned out, like accommodations and transportation?Sarah:Mostly, yes. We’ve booked our flights and hotels, and we’re using the Japan Rail Pass for getting around. B ut we’re leaving some room for spontaneity too. Sometimes the best experiences come unexpectedly!Man:Absolutely, that’s the spirit of traveling. Well, I hope you have an incredible time. Don’t forget to try some local food and maybe bring back some souvenirs!Sarah:Thanks, Mike! I definitely won’t miss out on trying sushi and ramen, and I already have a list of gifts to buy for family and friends. I can’t waitto share my adventures with everyone when I get back.1、How long is Sarah planning to stay in Japan?•A) One week•B) Two weeks•C) Three weeks•D) One month答案: B) Two weeks2、Which of the following ci ties is NOT mentioned as part of Sarah’s itinerary?•A) Tokyo•B) Kyoto•C) Sapporo•D) Hiroshima答案: C) Sapporo3、Who is Sarah going to Japan with?•A) By herself•B) With her family•C) With a group of friends•D) With coworkers答案: C) With a group of friends4、What has Sarah and her friends prepared for their trip besides booking flights and hotels?•A) They have hired a personal guide.•B) They have reserved spots for cultural workshops.•C) They have purchased a Japan Rail Pass.•D) They have enrolled in a language course.答案: C) They have purchased a Japan Rail Pass.四、听力理解-听力篇章(选择题,共20分)第一题Section CDirections: In this section, you will hear a passage three times. When the passage is read for the first time, listen carefully for its general idea. When the passage is read for the second time, fill in the blanks with the exact words you have just heard. Finally, when the passage is read for the third time, check what you have written.Passage:In recent years, the concept of “soft skills” has become increasingly popular in the workplace. These are skills that are not traditionally taught in schools but are essential for success in the professional world. Soft skills include communication, teamwork, problem-solving, and time management.1、Many employers believe that soft skills are just as important as technical skills because they help employees adapt to changing work environments.2、One of the most important soft skills is communication. Effectivecommunication can prevent misunderstandings and improve relationships with colleagues.3、Teamwork is also crucial in today’s workplace. Being able to work well with others can lead to better productivity and innovation.4、Problem-solving skills are essential for overcoming obstacles and achieving goals. Employees who can think creatively and solve problems efficiently are highly valued.5、Time management is another key soft skill. Being able to prioritize tasks and manage time effectively can help employees meet deadlines and reduce stress.Questions:1、What is the main idea of the passage?A) The importance of technical skills in the workplace.B) The definition and examples of soft skills.C) The increasing popularity of soft skills in the workplace.D) The impact of soft skills on employee performance.2、Why do many employers believe soft skills are important?A) They are easier to teach than technical skills.B) They are not necessary for most jobs.C) They help employees adapt to changing work environments.D) They are more difficult to acquire than technical skills.3、Which of the following is NOT mentioned as a soft skill in the passage?A) Communication.B) Leadership.C) Problem-solving.D) Time management.Answers:1、C) The increasing popularity of soft skills in the workplace.2、C) They help employees adapt to changing work environments.3、B) Leadership.Second Part: Listening Comprehension - Passage QuestionsListen to the following passage carefully and then choose the best answer for each question.Passage:Every year, millions of people flock to beaches around the world for their vacations. While enjoying the sun and sand, few give much thought to the tiny organisms that make up the very sand they’re lying on. Sand is actually made from rock particles that have been broken down over time by natural processes. However, on some unique beaches, like those found in Hawaii, the sand has a significant component of coral and shell fragments, giving it a distinctive white color. Beaches not only provide relaxation but also play a crucial role in supporting marine life and protecting coastal areas from erosion.Questions:1、What do millions of people go to the beaches for annually?2、What makes the sand on Hawaiian beaches distinctive?3、Besides providing relaxation, what other important role do beaches serve?Answers:1、Vacations.2、The presence of coral and shell fragments.3、Supporting marine life and protecting coastal areas from erosion.第三题PassageThe rise of e-commerce has revolutionized the way we shop. With just a few clicks, customers can purchase products from all over the world and have them delivered to their doorstep. However, this convenience has also brought about some challenges, particularly in terms of logistics and environmental impact.One of the biggest concerns is the environmental impact of packaging. Traditional packaging materials, such as plastic bags and boxes, are not biodegradable and often end up in landfills, contributing to pollution.E-commerce companies have started to address this issue by offering packaging-free options and promoting the use of sustainable materials.Another challenge is the issue of returns. With the ease of online shopping, customers often order more items than they need, leading to a high rate of returns. This not only increases the carbon footprint of shipping but also creates additional waste. Some companies have introduced policies to encourage customers to return fewer items, such as offering incentives for reuse or donation.Despite these challenges, the e-commerce industry is not standing still. There are innovative solutions being developed to make the process more sustainable. For example, some companies are experimenting with drone delivery to reduce the number of vehicles on the road. Others are investing in energy-efficient data centers to power their operations.1、What is one of the main concerns related to e-commerce packaging?A)The high cost of shipping materials.B)The environmental impact of non-biodegradable materials.C)The difficulty in recycling packaging materials.2、How does the high rate of returns affect e-commerce?A)It increases the demand for new packaging materials.B)It leads to a decrease in the cost of shipping.C)It creates additional waste and increases the carbon footprint.3、What is an innovative solution being developed to make e-commerce more sustainable?A)The use of reusable packaging.B)The implementation of strict return policies.C)The introduction of drone delivery.Answers:1、B2、C3、A五、阅读理解-词汇理解(填空题,共5分)First QuestionPassage:In today’s fast-paced world, conservation has become a major concern for environmentalists and policymakers alike. Preserving natural resources is not just about protecting the environment; it also plays a critical role in ensuring sustainable development and improving the quality of life for future generations. Innovative methods are being explored to achieve this goal, including the use of renewable energy sources and promoting eco-friendly practices in industries.Questions:1、The word “conservation” in the passage most likely means:A) The act of using something economically or sparingly.B) The protection of natural resources from being wasted.C) The process of changing something fundamentally.D) The act of restoring something to its original state.Answer: B) The protection of natural resources from being wasted.2、The word “innovative” in the passage is closest in meaning to:A) Outdated.B) Traditional.C) Creative.D) Unchanged.Answer: C) Creative.3、Based on the context, t he term “eco-friendly” would be best described as:A) Practices that are harmful to the environment.B) Practices that are beneficial to the environment.C) Practices that have no impact on the environment.D) Practices that focus solely on economic growth.Answer: B) Practices that are beneficial to the environment.4、The phrase “sustainable development” in the text refers to:A) Development that uses up all available resources quickly.B) Development that meets present needs without compromising the ability of future generations to meet their own needs.C) Development that focuses only on immediate economic gains.D) Development that disregards environmental concerns.Answer: B) Development that meets present needs without compromising the ability of future generations to meet their own needs.5、When the passage mentions “quality of life,” it implies:A) A decrease in living standards over time.B) An improvement in the overall conditions under which people live and work.C) The absence of any efforts to improve living conditions.D) The focus on increasing industrial activities regardless of their impact.Answer: B) An improvement in the overall conditions under which people live and work.This format closely follows the structure you might find in an actual CET Band 4 exam, with a passage followed by vocabulary questions that test understanding of context and word meanings.第二题Reading PassagesIn today’s fast-paced world, staying informed about current events is more important than ever. One of the best ways to keep up with the news is to read newspapers. However, not all newspapers are created equal. Here is an overview of some of the most popular newspapers in the world.1.The New York Times (USA): Established in 1851, The New York Times is one of the most prestigious and influential newspapers in the world. It covers a wide range of topics, including national and international news, politics, business, science, technology, and culture.2.The Guardian (UK): The Guardian is a British newspaper that has been in circulation since 1821. It is known for its liberal bias and its commitment to investigative journalism. The Guardian covers a variety of issues, including politics, the environment, and social justice.3.Le Monde (France): Le Monde is a French newspaper that was founded in 1944. It is one of the most widely read newspapers in France and is known for its in-depth reporting and analysis of global events.4.The Times (UK): The Times is another British newspaper that has been in circulation since 1785. It is a conservative newspaper that focuses on politics, business, and finance.5.El País (Spain): El País is a Spanish newspaper that was founde d in 1976. It is one of the most popular newspapers in Spain and is known for its comprehensive coverage of national and international news.Vocabulary UnderstandingChoose the best word or phrase to complete each sentence. Write your answers in the spaces provided.1、The____________of The New York Times is that it is one of the most prestigious and influential newspapers in the world.a.reputationb.historyc.popularityd.bias2、The Guardian is known for its____________bias and its commitment to investigative journalism.a.liberalb.conservativec.moderated.biased3、Le Monde is one of the most widely read newspapers in France and is known forits____________reporting and analysis.a.shallowb.superficialc.in-depthd.brief4、The Times is a conservative newspaper that focuses on____________issues.a.socialb.economicc.politicald.cultural5、El País is one of the most popular newspapers in Spain and is known for its comprehensive____________of national and international news.a.reportingb.analysisc.coveraged.editorialAnswers:1、a. reputation2、a. liberal3、c. in-depth4、c. political5、c. coverage六、阅读理解-长篇阅读(选择题,共10分)第一题Reading Passage OneIn recent years, with the rapid development of the internet and mobile technology, online learning has become increasingly popular among students. Online courses, such as those offered by MOOCs (Massive Open Online Courses), provide students with convenient access to high-quality educational resources from around the world. However, despite the benefits of online learning, there are also some challenges and considerations that need to be addressed.1.The following passage is about:A. The advantages and disadvantages of online learningB. The impact of online learning on traditional educationC. The history of MOOCs and their role in educationD. The challenges faced by students in online learning2.According to the passage, what is one of the main benefits of online learning?A. It allows students to study at their own paceB. It provides access to a wider range of educational resourcesC. It increases the interaction between students and teachersD. It reduces the cost of education3.The passage mentions that online learning has become increasingly popular due to:A. The advancements in internet technologyB. The decline of traditional education systemsC. The desire for flexible learning schedulesD. All of the above4.What is one of the challenges mentioned in the passage that online learners may face?A. Limited access to technological devicesB. Difficulty in maintaining self-disciplineC. Lack of face-to-face interaction with teachersD. All of the above5.The passage suggests that in order to succeed in online learning, students should:A. Attend online classes regularlyB. Engage in active discussions with peersC. Set clear goals and deadlines for their studiesD. All of the above答案:1.A2.B3.D4.D5.D第二题Reading Passage OneThe rise of the Internet has revolutionized the way we communicate and accessinformation. One of the most significant impacts has been the transformation of education, with online learning becoming increasingly popular. This passage explores the benefits and challenges of online learning.The Benefits of Online Learning1.Flexibility: Online learning offers students the flexibility to study at their own pace and on their own schedule. This is particularly beneficial for working professionals and those with other commitments.2.Access to a Wide Range of Resources: Online courses often provide access to a wealth of resources, including textbooks, videos, and interactive materials that can enhance the learning experience.3.Diverse Learning Opportunities: Online learning platforms offer a wide variety of courses, ranging from traditional academic subjects to specialized and niche areas of study.4.Cost-Effective: Online courses can be more affordable than traditional classroom-based programs, especially for those who live far from educational institutions.The Challenges of Online Learning1.Self-Discipline: Online learning requires a high level of self-discipline and motivation, as students must manage their time and stay focused without the structure of a traditional classroom.2.Limited Interaction: Online courses often lack the face-to-face interaction that is common in traditional classrooms, which can impact the learning experience and social development of students.3.Technical Issues: Online learning relies heavily on technology, which can lead to technical issues that disrupt the learning process.4.Quality Assurance: With the proliferation of online courses, ensuring the quality and integrity of these courses can be a challenge.Questions:1、What is one of the main advantages of online learning mentioned in the passage?A. It is more expensive than traditional education.B. It requires students to be self-disciplined.C. It provides flexibility in studying.D. It lacks face-to-face interaction.2、According to the passage, what can online learning platforms offer that traditional classrooms might not?A. Limited access to textbooks.B. Fewer specialized courses.C. More interactive learning materials.D. No video resources.3、Which of the following is a challenge that online learning may present?A. Students can easily attend classes at a local university.B. There are no technical issues with online learning.C. It is difficult to ensure the quality of online courses.D. Online learning is always more affordable than traditional education.4、The passage suggests that online learning can be beneficial for:A. Students who prefer face-to-face interaction.B. Individuals with other commitments.C. Those who want to avoid textbooks.D. People who have no access to technology.5、What is one potential drawback of online learning that the passage discusses?A. The ability to study at any time.B. The use of a wide range of resources.C. The possibility of technical disruptions.D. The convenience of studying from home.Answers:1、C2、C3、C4、B5、C七、阅读理解-仔细阅读(选择题,共20分)第一题Reading PassagesIn the following passage, there are some blanks. For each blank there arefour choices marked A, B, C, and D. You should choose the one that best fits into the passage.The digital revolution is changing the way we live, work, and communicate. One of the most significant changes is the rise of artificial intelligence (AI). AI refers to the development of computer systems that can perform tasks that typically require human intelligence, such as visual perception, speech recognition, and decision-making.The potential of AI is enormous. It has the potential to transform industries, improve efficiency, and make our lives more convenient. However, with great power comes great responsibility. The ethical implications of AI are complex and multifaceted.1、The passage is mainly aboutA. the benefits of the digital revolutionB. the rise of artificial intelligenceC. the challenges of the digital revolutionD. the ethical implications of AI2、What is the main concern regarding AI mentioned in the passage?A. Its potential to disrupt traditional industriesB. Its potential to replace human jobsC. Its potential to be used for unethical purposesD. Its potential to cause social inequalities3、The author suggests that AI has the potential to。
BECODISC BP 堆叠纤维过滤器筛卡型号说明书

Technical Data SheetDepth FiltrationBECODISC® BP RangeStacked Disc Cartridges for the Pharmaceutical IndustryBECODISC BP stacked disc cartridges meet thehigh demands of the pharmaceutical industry.Exceptionally pure raw materials and a specialproduction method produce BECODISC BPstacked disc cartridges with low endotoxincontent. The special characteristic of this range ishigh endotoxin retention during the filtration ofmany pharmaceutical products.The specific advantages of BECODISC BP stackeddisc cartridges:-High endotoxin retention as well as a maximumgerm retention rate.-The innovative production process guarantees anendotoxin content of less than < 0.125 EU/ml.-Maximum raw material purity for minimummigration of soluble ions.-The ideal combination of various filtrationmechanisms (surface, adsorption, depth filtration)and adsorptive properties ensures maximumreliability.-Comprehensive quality assurance for all raw andauxiliary materials and intensive in-processcontrols ensure consistent quality of the finishedproducts.-Prior to delivery, the pyrogen content of< 0.125 EU/ml of all BECODISC BP stacked disccartridges is tested with the help of an LAL test. Acertificate is available on request.- A Validation Guide is available upon request.Microbial Reduction and RemovalBECODISC B01P, B02P, B04PBECODISC stacked disc cartridges boast high microbial retention rates achieved through the tight-pored structure and an electrokinetic potential with an adsorptive effect.These stacked disc cartridges are characterized by high endotoxin retention rates. Due to their great retention capacity for colloidal components, these filter sheets are particularly suitable as prefilters for subsequent membrane filtration. Fine FiltrationBECODISC B08PBECODISC stacked disc cartridges for achieving a high degree of clarification. These stacked disc cartridges reliably retain ultra-fine particles and provide bioburden reduction.In practice, these depth filter sheets serve as ideal prefilters for protection of membrane filters, reverse osmosis systems, and to protect chromatography columns.Clarifying Filtration and Coarse Filtration BECODISC B20P, B40PBECODISC stacked disc cartridges with a large-volume pore structure. These stacked disc cartridges have a high dirt holding capacity for particles and arevery suitable for clarifying filtration applications.Physical DataThis information is intended as a guideline for the selection of BECODISC stacked disc cartridges. The water throughput is a laboratory value characterizing the different BECO depth filter sheets. It is not the recommended flow rate. Type*Utilized BECO ® depth filter sheet Nominal reten-tion rate µm Thickness in (mm) Ash content % Bursting strength wet psi (kPa**) Water throughput at Endo-toxin content*** EU/ml Δ p = 14.5 psi gpm/ft 2 (Δ p = 100 kPa** l/m 2/min) B01P PR Steril S100 0.1 0.15 (3.9) 58 > 7.3 (50) 0.7 (30) < 0.125 B02P PR Steril S80 0.2 0.15 (3.9) 50 > 11.6 (80) 1.1 (46) < 0.125 B04P PRSteril 40 0.4 0.15 (3.9) 49 > 7.3 (50) 1.5 (61) < 0.125 B08P PR 12 0.8 0.15 (3.9) 50 > 18.9 (130) 4.3 (175) < 0.125 B20P PR 5 2.0 0.15 (3.9) 50 > 8.7 (60) 8.1 (330) < 0.125 B40PPR 14.00.17 (4.3)48> 6.5 (45)58.4(2381)< 0.125* B = Polypropylene version (e.g. B01P) ** 100 kPa = 1 bar*** Endotoxin content analysis after rinsing with 1.23 gal/ft² (50 l/m²) of WFI (Water for Injection)Ordering Information1 Flat adapter/Double O-ring adapter |2 With cell spacer rail |3 Cannot be combined with double O-ring adapterExample: B01P62SFPolypropylene stacked disc cartridge with BECO PR Steril S100 depth filter sheets, nominal retention rate of 0.1 µm, 16 filter cells, 10.9 in (276 mm) high, 12", with silicone gaskets and flat adapter.BECODISC 12", Ø 11.6 in (295 mm) BECODISC 16", Ø 15.8 in (402 mm)Number of cells 16 14 91 9 5 16 14 91 9 5 Filter surface area [ft² (m²)]20.5 (1.9) 17.8 (1.65) 11.8 (1.1) 11.8 (1.1) 6.4 (0.59)39.8 (3.7) 34.4 (3.2) 22.6 (2.1) 22.6 (2.1) 12.4 (1.15)Pre-coat volume [gal (l)]²- 0.9 (3.6) 2.1 (8.0)- - - 1.8 (7.0) 4.1 (15.4)- - Overall height flat adapter [in (mm)]10.9 (276) 10.9 (276) 10.9 (276) 7.7 (195) 4.4 (101) 10.9 (276) 10.9 (276) 10.9 (276) 7.7 (195) 4.4 (101) Overall height double O-ring adapter [in (mm)] 13.0 (329) 13.0 (329) 13.0 (329) 10.0 (248) -13.0 (329) 13.0 (329) 13.0 (329) 10.0 (248) -Cell spacer rail- - ✓ - -- - ✓ - -1 Special stacked disc cartridge configuration with cell spacer rails providing increased mechanical stability forholding filter cake | 2 Calculated values (BECO depth filter sheets with 0.16 in/4.0 mm thickness)01PBECO depth filter sheet 01P = PR Steril S100 02P = PR Steril S80 04P = PR Steril 40 08P = PR 12 20P = PR 5 40P = PR 1BDesignB = Polypropylene6Construction(overall height)16 = 16 filter cells(10.9/13.0 in) (276/329 mm) 4 = 14 filter cells(10.9/13.0 in) (276/329 mm) 7 = 9 filter cells 2(10.9/13.0 in) (276/329 mm) 9 = 9 filter cells(7.7/10.0 in) (195/248 mm) 5 = 5 filter cells 3(4.4 in) (101 mm)2Size2 = 12", ∅ 11.6 in(295 mm) 4 = 16", ∅ 15.8 in(402 mm)SGasket material E = EPDM F = FEP-coatedsilicone core S = Silicone V = FluoroelastomerFAdapterF = Flat adapter S = Double O-ringadapter Y = Flat adapter withgrounding deviseCompliance NoticeBECO depth filter sheets fulfill the requirements of Regulation (EC) 1935/2004 as well as the FDA Guideline 21 CFR § 177.2260 test criteria. The polypropylene components comply with Regulation (EU) 10/2011. The polypropylene meets FDA requirements, 21 CFR § 177.1520. The sealing materials (silicone, EPDM) meet FDA requirements, 21 CFR § 177.2600. The depth filter sheet and the polypropylene components of the BECODISC BP stacked disc cartridges meet the requirements of the USP Plastic Class VI – 70 °C test. For further details on individual components and materials see the declaration of conformity.Pyrogens/EndotoxinsPyrogens are biological or chemical substances that can induce a rise in body temperature. One common example is endotoxins. These are cell wall components known as lipopolysaccharides that are embedded in the outer membrane of gram-negative bacteria.Quantitative evidence of endotoxins can be determined using the LAL test (L imulus A mebocyte L ysate). This method is an efficient and economical alternative to the rabbit fever test. An independent institute examines the depth filter sheets.The endotoxin content of the specimens examined is specified in EU/ml (E ndotoxin U nits).The measurement is carried out after rinsing with1.23 gal/ft² (50 l/m²) of WFI water.Endotoxin Retention RateTo measure endotoxin retention, a 40% glucose solution containing a defined amount of lipopolysaccharide (LPS) in pyrogen-free water is passed through a depth filter sheet. A defined sample of the filtrate is then measured by means of the LAL test.Filtration flow rate: 12.3 gal/ft2/h(500 l/m2/h)Sampling after: 1.23 gal/ft² and 6.14 gal/ft²(50 l/m2 and 250 l/m2)Amount of endotoxinadded: 2.2 mg LPS E. Coli 055:B5, thisequals 4.4 µg LPS/ml or4.4 x 104 EU/mlThe endotoxin retention rate is indicated in the following graphic.Endotoxin retention rate of BECODISC BP stacked9897ComponentsThe depth filter sheets for the BECODISC BP stacked disc cartridges are manufactured from particularly pure materials, i.e., finely fibrillated cellulose fibers from deciduous and coniferous trees, cationic charge carriers, and high-quality, particularly pure diatomaceous earth.Recommendations for Avoiding Damage BECODISC stacked disc cartridges can be used only in the specified flow direction. This applies to product filtering as well as sanitizing with hot water, and sterilizing with the stacked disc cartridges with saturated steam. In order to avoid damage to the filter cells, the system should be protected with a suitable non-return valve. Refer to the insert included with each BECODISC stacked disc cartridge carton for detailed application information.Depending on the filtered liquids, the operating temperature should not exceed 176 °F (80 °C). Please contact Eaton regarding filtration applications at higher temperatures.Intermediate PlatesIf more than two BECODISC stacked disc cartridges (12" or 16") with double O-ring adapters are stacked in the housing, install a central spindle for safety reasons. In the event, more than one 16" BECODISC stacked disc cartridge (flat adapter/double O-ring adapter) is used in the housing, Eaton recommends the installation of stainless steel intermediate plates between the BECODISC stacked disc cartridges. When silicone/FEP coated gaskets are used the stainless steel plates are mandatory.Sanitizing and Sterilizing (Optional)Sterilizing with Hot WaterThe hot water temperature should be 185 °F (85 °C). A differential pressure of 21.8 psi (150 kPa, 1.5 bar) must not be exceeded when sterilizing with hot water. Sterilization time: At least 30 minutes once a temperature of 185 °F (85 °C) is reached at all filter openings. In the interest of energy conservation, the water may be circulated provided the specified temperatures are maintained.Sterilizing with SteamThe wetted BECODISC stacked disc cartridges can be sterilized with saturated steam up to a maximum temperature of 250 °F (121 °C) as follows:Steam quality: The steam must free of foreignparticles and impurities. Temperature: Max. 250 °F (121 °C)(saturated steam)Duration:Approx. 20 minutes after steam exitsfrom all filter valves.Rinsing: After sterilizing with 1.23 gal/ft²(50 l/m²) at 1.25 times the flow rate. Filter Preparation and FiltrationUnless already completed after sterilization, Eaton recommends pre-rinsing the closed filter with1.23 gal/ft² (50 l/m²) of water at 1.25 times the flow rate prior to the first filtration. Depending on the application, this usually equals a rinsing time of10 – 20 minutes. Test the entire filter for leakage at maximum operating pressure.High-proof alcohol solutions and products that do not allow pre-rinsing with water should be circulated for 10 to 20 minutes. Dispose of the rinsing solution after rinsing.Differential PressureTerminate the filtration process once the maximum permitted differential pressure of 43.5 psi (300 kPa,3 bar) is reached. A higher differential pressure could damage the depth filter sheet material. For safety reasons, a differential pressure of 21.8 psi (150 kPa, 1.5 bar) should not be exceeded in applications for separating microorganisms.SafetyWhen used and handled correctly, there are no known unfavorable effects associated with this product. Further safety information can be found in the relevant Material Safety Data Sheet, which can be downloaded from our website. Waste DisposalDue to their composition, BECODISC stacked disc cartridges can be disposed of as harmless waste. Comply with relevant current regulations, depending on the filtered product.StorageBECODISC stacked disc cartridges must be stored in a dry, odor-free, and well ventilated place.Do not expose the BECODISC stacked disc cartridges to direct sunlight.BECODISC stacked disc cartridges are intended for immediate use and should be used within 36 months after production date.Quality Assurance According to DIN EN ISO 9001The Quality Management System of Eaton Technologies GmbH has been certified according to DIN EN ISO 9001.This certification verifies that a fully functioning comprehensive Quality Assurance System covering product development, contract controls, choice of suppliers, receiving inspections, production, final inspection, inventory management, and shipment has been implemented.Extensive quality assurance measures incorporate adherence to technical function criteria and chemical purity and quality recognized as safe under the German legislation governing the production of foods and beverages.All information is given to the best of our knowledge. However, the validity of the information cannot be guaranteed for every application, working practice and operating condition. Misuse of the product will result in all warrantees being voided.Subject to change in the interest of technical progress.North America44 Apple StreetTinton Falls, NJ 07724Toll Free: 800 656-3344(North America only)Tel: +1 732 212-4700Europe/Africa/Middle EastAuf der Heide 253947 Nettersheim, Germany Tel: +49 2486 809-0Friedensstraße 4168804 Altlußheim, Germany Tel: +49 6205 2094-0An den Nahewiesen 2455450 Langenlonsheim, Germany Tel: +49 6704 204-0 Greater ChinaNo. 7, Lane 280,Linhong RoadChangning District, 200335Shanghai, P.R. ChinaTel: +86 21 5200-0099Asia-Pacific100G Pasir Panjang Road#07-08 Interlocal CentreSingapore 118523Tel: +65 6825-1668For more information, pleaseemail us at ********************or visit /filtration© 2021 Eaton. All rights reserved. All trademarks andregistered trademarks are the property of their respectiveowners. All information and recommendations appearing inthis brochure concerning the use of products describedherein are based on tests believed to be reliable. However,it is the user’s responsibility to determine the suitability forhis own use of such products. Since the actual use byothers is beyond our control, no guarantee, expressed orimplied, is made by Eaton as to the effects of such use orthe results to be obtained. Eaton assumes no liabilityarising out of the use by others of such products. Nor is theinformation herein to be construed as absolutely complete,since additional information may be necessary or desirablewhen particular or exceptional conditions or circumstancesexist or because of applicable laws or governmentregulations.EN1 A 2.5.5.9.09-2021。
chemical images

Efficient encoding and rapid decoding for interactive visualization of large three-dimensional hyperspectral chemical imagesStephen E.Reichenbach1*,Alex Henderson2,Robert Lindquist1and Qingping Tao3 1Department of Computer Science and Engineering,University of Nebraska–Lincoln,Lincoln,NE68588-0115,USA2Surface Analysis Research Centre,Manchester Interdisciplinary Biocentre,University of Manchester,Manchester M17DN,UK3GC Image,LLC,Lincoln,NE68506,USAReceived28October2008;Revised23January2009;Accepted23January2009Interactive visualization of data from a new generation of chemical imaging systems requires coding that is efficient and accessible.New technologies for secondary ion mass spectrometry(SIMS) generate large three-dimensional,hyperspectral datasets with high spatial and spectral resolution.Interactive visualization is important for chemical analysis,but the raw dataset size exceeds the memory capacities of typical current computer systems and is a significant obstacle.This paper reports the development of a lossless coding method that is memory efficient,enabling large SIMS datasets to be held in fast memory,and supports quick access for interactive visualization.The approach provides pixel indexing,as required for chemical imaging applications,and is based on the statistical characteristics of the data.The method uses differential time-of-flight to effect mass-spectral run-length-encoding and uses a scheme for variable-length,byte-unit representations for both mass-spectral time-of-flight and intensity values.Experiments demonstrate high compression rates and fast access.Copyright#2009John Wiley&Sons,Ltd.The lossless coding scheme described in this paper facilitates rapid visualization and analysis of large,multi-dimensional, hyperspectral datasets generated by a new generation of chemical imaging systems such as the time-of-flight secondary ion mass spectrometry(ToF-SIMS)instrument developed by Vickerman and co-workers at the Manchester Interdisciplinary Biocentre(MIB)in conjunction with Ionoptika(Chandler’s Ford,UK).1In ToF-SIMS,a beam of primary ions is directed onto a target,eroding molecules and molecular fragments as neutral species and ions(i.e. secondary ions)from the target surface(as illustrated in Fig.1).The secondary ions that are eroded from the target surface are electrostatically accelerated to a detector that measures their intensity as a function offlight time–data that can be converted into mass spectra.2The primary-ion beam can be directed in a raster pattern to create a mass-spectral image and the raster scanning can be repeated to generate a three-dimensional(3D)mass-spectral image,as illustrated in Fig.2.The Ionoptika J1053D chemical imager has been detailed elsewhere.1Briefly,it combines several advances,including polyatomic primary-ion beams and an advanced buncher for secondary ions that facilitates a continuous-beam primary-ion probe.Polyatomic primary-ion beams(e.g.buckmin-sterfullerene,[C60]þ)provide greater secondary-ion yield, more uniformity in the secondary-ion yield,and less damage to the substrate of the target than traditional primary-ion beams.3Greater yield improves the signal-to-noise ratio and sensitivity.Improved uniformity enhances effective resol-ution and allows more accurate mapping of chemical constituents.With reduced sub-surface degradation,as the surface is eroded,subsequent scans across the target yield more accurate depth profiling to improve3D chemical imaging.An innovative secondary-ion buncher shapes the electricfield that propels the secondary ions for the time-of-flight(ToF)mass spectrometer,thereby focusing the vari-able-sized,variable-positioned secondary ions.Time focus-ing obviates the need to pulse the primary-ion beam to limit the time range of the secondary ions,which allows quasi-continuous operation of the primary-ion beam.The con-tinuous primary-ion beam provides faster analyses and increased spatial resolution.The system then uses a harmonic-field reflectron with the property that the time-of-flight in and out of the reflector depends on mass-to-charge only(and not on their variable energy).This creative design provides high-precision mass spectrometry even with continuous operation of the primary-ion beam.The system’s high spatial resolution,fine mass precision, and high-sensitivity surface and depth-profile characteriz-ations of the molecular chemistry of heterogeneous materials,including biological tissues and cells,promise toRAPID COMMUNICATIONS IN MASS SPECTROMETRYRapid Commun.Mass Spectrom.2009;23:1229–1233Published online in Wiley InterScience()DOI:10.1002/rcm.3962*Correspondence to:S.E.Reichenbach,260Avery Hall,Universityof Nebraska–Lincoln,Lincoln,NE68588-0115,USA.E-mail:reich@Contract/grant sponsor:UK Engineering and Physical SciencesResearch Council;contract/grant number:EP/FO12985.Contract/grant sponsor:The Faculty Development Leave Pro-gram of the University of Nebraska–Lincoln.Contract/grant sponsor:The USA National Science Foundation;contract/grant numbers:IIS-0431119and IIP-0741027NER/O/S/2003/00667.Copyright#2009John Wiley&Sons,Ltd.provide an informational basis for important advances in a wide variety of applications,including cancer treatments.However,the volume of data produced poses a significant challenge for interactive visualization and analysis.When fully operational,this ToF-SIMS instrument will produce 3D datasets of the order of 5123spectra with tens of thousands of ToF channels.In the example datasets presented here,individual mass spectra are sampled in up to 85000ToF channels at a rate of 1ns per 8-bit intensity (a raw data rate of 1gigabyte per second)and accumulated in hardware with an Ortec Fastflight-2TM (Oak Ridge,TN,USA).In the example datasets,200to 1000raw spectra are accumulated per pixel,but the number may be larger or smaller depending on the application.If no more than 256spectra are accumulated,each accumulated intensity can be represented with a 16-bit unsigned integer in the raw data file,reducing the data rate to 10megabytes per second (MB/s).However,a 128Â128,16-layer image with 850002-byte ToF channels requires 45gigabytes (GB)without com-pression and even a single two-dimensional slicewithFigure 1.Primary ions directed at the target erode second-ary ions for analysis by mass spectrometry.Figure 2.A 3D SIMS image colorized for intensity in mass spectral ranges.(Data from Fletcher et al .3Visualization and analysis software from GC Image,LLC.)This figure is available in color online at www.interscience.wiley .com/journal/rcm.Copyright #2009John Wiley &Sons,Ltd.Rapid Commun.Mass Spectrom.2009;23:1229–1233DOI:10.1002/rcm1230S.E.Reichenbach et al.512Â512data points with 85,0002-byte ToF channels requires 45GB.Datasets of tens to hundreds of gigabytes cannot be held in the fast memory of typical computer systems,which creates a bottleneck for interactive visual-ization and analysis with general-purpose imaging software.Real-time,interactive,3D visualization and analysis require memory-efficient coding.The most important access mode for interactive SIMS visualization is retrieving spectra by pixel (i.e.spatial position).Analysts determine chemical compositions on the basis of mass-spectral characteristics,so viewing of the mass spectra is mon interactive oper-ations are to view the mass spectrum at a point in the image space indicated by point-and-click and to view the mass spectrum summed over a spatial region indicated by drawing.An important operation is to generate a classifi-cation rule(s)based on mass spectra in two (or more)regions.Analysts also view a mass-spectral range (e.g.for a selected ion)across the image space,but such spectral-spatial viewing does not require immediate interactivity to the degree required in pixel-oriented spatial-spectral access.Moreover,operations to generate spatial maps from their spectra require pixel-by-pixel access to many or all ToF channels,e.g.to map regions that satisfy a classification rule.Tretter et al .4cite two approaches among methods for lossless compression of hyperspectral images:predictive coding and reversible transforms,each followed by context modeling and coding.Both approaches can be applied either with respect to the spatial dimensions or to the spectral dimension (or both).Predictive coding has been the predominant approach for hyperspectral data.Lossless transform coding methods for hyperspectral data are newer and typically require greater computation than lossless predictive methods,but may achieve greater compression.Given the motivation of interactive visualization and analysis of SIMS data,low computational complexity is more important than optimal compression,so the more traditional approach of predictive coding may be better suited.Given the primary need for spatial access in SIMS analysis,each pixel spectrum should be compressed separately.This paper describes a new approach that codes individual spectra,consistent with the predominant access mode for SIMS analysis,based on statistical and structural character-istics of SIMS spectra.Unlike some hyperspectral data generated by remote sensing satellites,for which many hyperspectral compression methods have been developed,SIMS spectra have many zero values and the probability distribution of the intensity values is skewed significantly,decreasing rapidly with magnitude.In addition,many of the non-zero values are in adjacent ToF channels,forming peaksin the mass spectra.Other technologies,such as matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)and confocal fluorescence or Raman micro-scopy,may produce data with similar statistical character-istics,in which case the approach described here would be applicable.As described in the next section,these statistical characteristics can be exploited to give highly compressed data that can be accessed quickly.SIMS DATA CHARACTERISTICSThe most notable characteristic of SIMS hyperspectral data is that many of the intensity values are zero.As shown in Table 1,more than 96%of all intensity values in each of the example datasets are zero.(The datasets are divided into units smaller than 2GB to facilitate experimental processing.)For example,of the 1380million spectral intensities for target 20071213z0(128Â128with 85000ToF channels),only 38million non-zero intensities are recorded.This character-istic of the data reflects the fact that the number of chemical constituents at a sample point of the target limits the number of secondary ions and therefore the number of peaks in each mass spectrum.Another important characteristic of the data is that the probability distribution of the intensity values decreases with intensity.Many of the non-zero values are equal to one (many of which may be noise but must be coded in a lossless method)and most non-zero values are less than 256.Because of the large number of zero values and the long-tailed skewed probability distributions,least-squares predictors,which are effective for remote sensing data,do not perform well for SIMS data.For example,with the example dataset 20071213z0,the optimal least-squares predictor based on the previous intensity value in the spectrum reduces the variance in the residual (from that variance of the data),but increases the entropy to 0.45bits/value compared with the original dataset entropy of 0.34bits/value.(Entropy iscomputed as Pi P[i ]lg(P[i ]),where i is each intensity value and P[i ]is the probability of the intensity value.)Another characteristic of the datasets is that peaks in the mass spectra may be wider than the ToF channels,so each mass-spectral peak may cause several non-zero values in adjacent ToF channels.The high probability of zero values and the clustering of non-zero values suggest that run length encoding may be used to effectively code the long runs of zeros between non-zero monly used sparse array representations of mass spectra (i.e.recording the mass and value for each non-zero value)similarly take advantage of the large number of zeros to efficiently represent MS data.If,instead of the ToF channel index,the differential of indexes of non-zero-valued channels is used (i.e.theTable 1.Intensity probability distributions (%)Dataset Count(M)P(x ¼0)P(x ¼1)P(1<x <28)P(28 x <216)P(216 x)Entropy GridSpot 93896.85 1.08 1.870.210.000.3620071213z0138097.220.31 2.480.000.000.3420071213z1137198.040.22 1.750.000.000.2520071213z2136098.650.151.200.000.000.18Copyright #2009John Wiley &Sons,Ltd.Rapid Commun.Mass Spectrom.2009;23:1229–1233DOI:10.1002/rcmVisualization of large 3D hyperspectral chemical images 1231difference between the index of the next channel with a non-zero value and one more than the index of the current non-zero channel),the result is a run length code.For example,if the channels with non-zero values are 7,50,89,188,189,198,199,200,...;then the differentials of the indices are 6,42,38,98,0,8,0,0,...,which are just the run lengths of the zeros.The probability distribution and entropy of the example ToF differentials is shown in Table 2.Because the non-zero values tend to be clustered,more than half of the ToF differentials in each of the example datasets are equal to zero.Many of the other differentials are less than 256.For the dataset 20071213z0,the total entropy of the ToF differentials (entropy per value times number of values)is 17MB with only 38million non-zero intensities to be coded.This approach is the basis of the method described in the next section.SIMS DATA COMPRESSIONBased on the SIMS data characteristics,the method developed here separately codes the ToF differentials and non-zero intensity values.Because many of the ToF differentials are zero,it is important to code them most efficiently.Because the compressed data will be decoded for visualization,the approach uses representations of integer byte-lengths which do not require computation for decoding –just byte copies.Accordingly,the method uses 2-bit length codes to record the number of bytes for each ToF differential and zero bytes are used if the differential is zero.The length codes (in binary)are:00if the differential is zero,with no separate representation of the differential;01if the differential is in the range 1–255,with the differential coded in one byte;10if the differential is in the range 256–65535,with the differential is coded in two bytes;and 11if the differential is 65536or larger,with the differential coded in four bytes.Thus,only two bits are required for the ToF differentials that are equal to zero,10bits are required for the ToF differentials in the range 1–255,etc.For the example above,with ToF differentials 6,42,38,98,0,8,0,0,...,the length codes would be 0101010100010000(two bytes in binary)and the differential codes would be 062A266208(five bytes in hexadecimal).The differential codes can be retrieved quickly using byte copies.For the dataset 20071213z0,this coding of the ToF differentials requires 24MB,compared with the total entropy of 17MB,but allows very rapid decoding (as documented in the next section)at the cost of a relatively small difference in compression.The non-zero intensity values could be compressed by any method,but the scheme used for the ToF differentials can be used and is justified by the significant number of ones and small values.The integer byte-length scheme also allows quick retrieval of the intensity for a specific channel,decoding only the ToF differentials and the intensity byte-lengths to locate the byte(s)with the intensity value.Thus,here,the non-zero intensity values are reduced by one (so that the smallest value to be recorded,which is one,is mapped to zero)and then coded using the length-coding scheme described above.For the dataset 20071213z0,this coding of the non-zero values requires 44MB,compared with a total entropy of 27MB for the non-zero values,but here also decoding requires only byte copies and is very fast (as documented in the next section).RESULTSThis section compares the speed and compression of the proposed SIMS compression method with GZIP (in java.util.zip 5),arithmetic coding with an adaptive unigram model (in com.colloquial.arithcode 6),and arithmetic coding with Prediction by Partial Matching 7,8(PPM(3)in com.colloquial.arithcode).Each method was applied separately to each of the spectra in each of the datasets.Table 3summarizes the compression times and sizes.(The raw dataset type for each intensity is a four-byte integer.)PPM(3)with arithmetic coding requires more computation but achieves better compression than the adaptive unigram model with arithmetic coding,and the adaptive unigram model with arithmetic coding requires more computation but achieves better compression than GZIP.These results are as expected.The SIMS coding method achieved the greatest compression,but more importantly was very rapid.The encoding times for the SIMS method were less than 30%ofTable pression and decompression times and sizesDatasetGZIP Adaptive Unigram PPM(3)SIMS Name Size (MB)Encode time(s)Decode time(s)Size (MB)Encode time(s)Decode time(s)Size (MB)Encode time(s)Decode time(s)Size (MB)Encode time(s)Decode time(s)Size (MB)Grid Spot 3750882876162118465617432546542615020071213z055201344098238627397427604172733816820071213z154861264072238027355525013669533714820071213z2544012341522414278841234733453837133Table 2.ToF differential probability distributions (%)Dataset Count(M)P(d 0¼0)P(0<d 0<28)P(28 d 0<216)P(216 d 0)Entropy GridSpot 3054.1843.78 2.040.00 4.3620071213z03865.0031.60 3.400.00 3.6020071213z12764.6430.44 4.920.00 3.7620071213z21864.3428.776.940.003.94Copyright #2009John Wiley &Sons,Ltd.Rapid Commun.Mass Spectrom.2009;23:1229–1233DOI:10.1002/rcm1232S.E.Reichenbach et al.the times for GZIP.More importantly,the decompression times for the SIMS method were less than 3%of the times for GZIP.Decompression is especially fast because only the bytes for the non-zero intensities must be copied into the output array.The compression rate for all methods would enable fairly large ToF-SIMS datasets to be stored in the memory of current desktop systems (typically 2–8GB).Pixel mass spectra are compressed to an average of about 3kB to 6kB,so with any of the methods a typical memory could hold more than 1M spectra (e.g.a 1024Â1024slice or even a 643or 1283visualization data cube).The performance of the SIMS method,both for compression and decoding speed,is excellent.CONCLUSIONSThis paper describes the development of a new coding method for multi-dimensional hyperspectral data generated by advanced chemical imaging systems,such as ToF-SIMS.The method is designed based on data characteristics to provide indexed access to pixel spectra with very rapid decoding.Experimental results indicate that the method achieves memory-efficient compression and provides quick access.Although the method was developed and tested for ToF-SIMS data,it should be effective for other sparse hyperspectral data with predominantly small values and skewed probability distribution.AcknowledgementsThis work was supported by the UK Engineering and Physical Sciences Research Council’s ‘‘Collaborating for Suc-cess through People’’funding to John C.Vickerman (EP/FO12985),by the Faculty Development Leave program of the University of Nebraska –Lincoln,and by the USA National Science Foundation funding to S. E.Reichenbach (IIS-0431119)and Q.Tao (IIP-0741027).The authors gratefully acknowledge the support and data provided by John Vicker-man and John Fletcher of the Surface Analysis Research Centre at the University of Manchester.REFERENCES1.Fletcher JS,Rabbani S,Henderson A,Blenkinsopp P,Thompson S,Lockyer NP,Vickerman JC.Anal.Chem.2008;80:9058.2.Vickerman JC.In ToF-SIMS:Surface Analysis by Mass Spec-trometry ,Vickerman JC,Briggs D (eds).SurfaceSpectra:Manchester,UK,2001.3.Fletcher JS,Lockyer NP,Vaidyanathan S,Vickerman JC.Anal.Chem.2007;79:2199.4.Tretter D,Memon N,Bouman CA.In Handbook of Image and Video Processing ,Bovik A (ed).Academic Press:San Diego,2000.5.Sun Microsystems.Package java.util.zip .Available:/j2se/1.5.0/docs/api/java/util/zip/package-summary.html/.6.Carpenter B.Arithmetic Coding .Available:/ArithmeticCoding/javadoc/index.html.7.Cleary JG,Witten IH.IEEE put.1984;32:396.8.Witten IH,Neal R,Cleary mun.ACM 1987;30:520.Copyright #2009John Wiley &Sons,Ltd.Rapid Commun.Mass Spectrom.2009;23:1229–1233DOI:10.1002/rcmVisualization of large 3D hyperspectral chemical images 1233。
化学农业有什么优点英语作文

化学农业有什么优点英语作文英文回答:Chemical agriculture, also known as conventional agriculture, has been widely practiced for decades and has several advantages that have contributed to its prevalence.1. High Productivity: Chemical agriculture employs the use of synthetic fertilizers, pesticides, and herbicides, which significantly increase crop yields. These inputs enhance soil fertility, control pests and diseases, and suppress weeds, resulting in higher crop production levels. This increased productivity has helped meet the growing global food demand and reduce hunger and malnutrition.2. Predictable and Consistent Results: Chemical agriculture provides farmers with predictable and consistent results by controlling the variables that affect crop growth. By using standardized fertilizers and pesticides, farmers can maintain consistent crop yields andreduce the risk of crop failures. This predictability allows for better planning and forecasting of agricultural production.3. Cost-Effectiveness: While chemical inputs may have high upfront costs, they often lead to increased yields, which can offset these expenses. The use of chemical fertilizers and pesticides can reduce labor costs associated with manual weeding and pest control. Additionally, chemical agriculture enables farmers to cultivate larger areas of land, further increasing their economic returns.4. Reduced Labor Requirements: Chemical agriculture relies on machinery and chemical inputs rather than intensive manual labor. This has significantly reduced the labor requirements for farming, allowing farmers to manage larger operations with fewer workers. The mechanization of agriculture has also improved efficiency and reduced the physical demands on farmers.5. Improved Quality and Shelf Life: Chemicalagriculture can enhance the quality and shelf life of produce. Pesticides and herbicides help protect crops from pests and diseases that can damage their appearance and reduce their market value. Additionally, fertilizers promote healthy plant growth, resulting in crops withhigher nutritional content and better flavor.中文回答:化学农业的优点:1. 高产性,化学农业采用化肥、农药、除草剂等投入品,大幅提高作物产量。
chemical genetics

Chemical Genetics †Daniel P.Walsh and Young-Tae Chang*Department of Chemistry,New York University,New York,New York 10003Received April 22,2005(Revised Manuscript Received March 30,2006)Contents1.Introduction24762.Chemical Toolboxes 24792.1.Natural Products24792.2.Natural-Product-Like Compounds 24802.3.Diversity Oriented Synthesis 24802.4.Tagged Libraries24822.5.Target Guided Ligand Assembly 24852.6.Dynamic Combinatorial Libraries 24862.7.Annotated Chemical Libraries 24873.Screening:An Overview24874.Forward Chemical Genetic Screening 24894.1.Yeast 24894.2.Plants 24914.3.Zebrafish 24934.4.Drosophila24944.5.Caenorhabditis elegans 24954.6.Mammalian Cells24954.6.1.Phenotypic Screening 24954.6.2.Cytoblot24974.6.3.Gene Reporter24994.6.4.Fluorescent Imaging25014.7.Chemical Genetic Networks andMultidimensionality 25034.8.Cell-Free Systems25045.Reverse Chemical Genetic Screening 25055.1.In Vitro Screening25055.2.Chemical Inducers of Dimerization 25065.3.Orthogonal Chemical Genetics25085.4.Disruption of Protein −Protein Interactions 25115.5.Targeted Protein Degradation 25125.6.Screening on Beads25135.7.Wide-Angle X-ray Solution Scattering 25135.8.Gene Expression Regulation 25145.9.Small-Molecule Microarrays 25155.10.Phenotypic Response 25166.Target Identification 25177.Conclusion 25228.Abbreviations 25239.Acknowledgment 252310.References25231.IntroductionChemical genetics,in the simplest terms,can be defined as a “genetics”study using “chemical”tools.1,2Classical genetics may study a gene function by directly removing a†This paper is dedicated to Professor Sung-Kee Chung,my lifetime mentor,on the occasion of his 60th birthday.*To whom correspondence should be addressed.E-mail:yt.chang@.Phone:(212)998-8495.Fax:(212)260-7905.Daniel Walsh was born in Shenandoah,Pennsylvania.He attended the University of Scranton and performed undergraduate research with Dr.Paul T.Buonora.He conducted his Ph.D.work with Dr.Young-Tae Chang at New York University.His research in Chemical Genetics focused on developing small molecule microarrays and chemical probes that target tubulin.He is currently a Hazardous Materials/WMD Specialist with the New York City Department of Environmental Protection.Young-Tae Chang was born in Busan,Korea,in 1968.He studied chemistry in Pohang University of Science and Technology (POSTECH,Korea)and received his B.S.in 1991.After one and half years of army service in Korea,he started his graduate study at POSTECH and received a Ph.D.in 1997under the supervision of Prof.Sung-Kee Chung,working on the divergent synthesis of all possible regioisomers of myo -inositol phosphates.He did his postdoctoral work with Prof.Peter Schultz at UC Berkeley and The Scripps Research Institute.In 2000,he was appointed assistant professor at New York University and promoted to associated professor in 2005.He received the NSF Career award in 2005and his research interests include chemical genetics,molecular evolution,and artificial tongues.2476Chem.Rev.2006,106,2476−253010.1021/cr0404141CCC:$59.00©2006American Chemical SocietyPublished on Web06/14/2006gene product(s),proteins (genetic knockout),from the organism.In contrast,chemical genetics indirectly studies a gene’s role by altering the activity of the cognate protein,using small molecule inhibitors analogously to the genetic knockout.1,3,4As is classical genetics,chemical genetics is divided into two approaches,forward and reverse (Figures 1and 2).Forward genetics (FG)operates “from effect to cause”or “phenotype (physically apparent characteristic)to genotype (genetic sequence)”and requires no specific gene target from the onset.4-6It studies changes in phenotype(s)such as morphology,growth,or behavior resulting from random genomic DNA mutations or deletions induced from radio-active or chemical mutagenesis and then identifies the gene responsible through mutation mapping.3,7,8Forward chemical genetics (FCG)mimics FG by substituting random mutagen-esis with a collection of a library of typically unbiased (not targeted)compounds as protein function regulators in place of mutagens.9The first step in both FG and FCG is to screen for changes induced by either the inhibition or stimulation of a protein’s function,and both go on to identify the genetic cause,but in different ways.FG goes after genetic mutation,a permanently retained marker,but FCG needs to identify the protein partner for the small molecule.This target identification is one of the greatest challenges in chemical genetics.6,10-13With the help of molecular biology techniques,reverse genetics (RG)was a later development in genetics and operates “from cause to effect”(genotype to phenotype).4,14Reverse genetics begins with selecting a gene of interest,manipulating it to produce an organism harboring the mutated gene,and characterizing the phenotypic differences between the mutant and the wild-type organisms.7,13In the same context,reverse chemical genetics (RCG)begins with a known protein,analogous to a specific gene selection.5This known protein is then screened with vast pools of library compounds to identify functional ligands that either stimulate or inhibit the target protein.15Once a specific ligand is identified,it is introduced to a cell or organism,analogous to genetic mutation,and the resulting changes in phenotype are studied.5Compared to classical genetics,chemical genetics offers a number of advantages and provides access to previously unstudied biological space.16Use of chemical tools offers greater ease and flexibility than classical genetic modifica-tion.Classical genetic techniques are relatively difficult to employ,especially in mammals due to their diploid genome,physical size,and slow reproduction rate,though great progress has been made in this area.17-23On the other hand,chemical genetics studies may be conducted on any complex cellular or animal models without any time-consuming genetic modifications that may prove lethal or in which the cell/animal can mask the phenotype through related gene functional compensation for the mutation.4,8,14,24Especially important is chemical genetics’promise of operating in the relevant context of human cells at physiological conditions that has strained traditional genetics techniques.25Therefore,chemical genetics fills a major gap in genetic studies where no,or suboptimal,model systems exist.26Additionally,chemical genetics also allows for the possibility of “multiple knockouts”by adding multiple specific ligands,a situation often described as a “nightmare”for a geneticist.27Figure 1.Forward genetics begins with a wild-type cell or organism that has its DNA mutated via chemical-or radiation-induced mutagenesis.The organisms are then screened for changes in phenotypes of interest,and that phenotype is selected out.The selected cell/organism is then analyzed to identify the mutated gene responsible by gene mapping.Reverse genetics begins with the selective targeted mutation of a gene.The phenotype induced is observed,and the mutant is compared to the wild-type to determine the gene’s function.Chemical Genetics Chemical Reviews,2006,Vol.106,No.62477Additionally,classical genetic knockouts,in principle,delete the protein entirely from the organism.3Therefore,it is difficult to determine effects that arise from the deletion separately from those that arise from merely a particular function of the protein.28It is always possible that one protein may have multiple functions,and chemical genetics can potentially isolate and dissect particular functions of that protein while leaving others intact.24Additionally,if a gene is essential for survival or development,a total knockout,such as in classical genetics,may abolish the chance to study the later stage function of that gene since the deletion may be lethal.29Chemical genetics allows the use of sublethal doses of the ligand and avoids full lethality,thus providing a partial knockout phenotype.30Another advantage of chemical genetics is real-time control.Chemical genetics allows for this by rapidly introducing a cell-permeable ligand at any stage that may yield the desired phenotype as quickly as diffusion-limited kinetics allows.10,14The chemical perturber/ligand/probe is in effect a “switch”that can turn the event under study on or off in real time and allows for kinetic in vivo analysis,something not usually possible in classical genetics.6,17While temporal control is available in classical genetic studies through conditional alleles,such as temperature-sensitive mutations,these alleles often have unwanted broad side effects that may interfere with the desired result.14Antisense oligonucleotide and RNA interference (RNAi)are other popular alternatives for conditional knockouts 12,28,29that work by inhibiting the synthesis of the target protein from mRNA.However,because their effects are delayed until all of the already existing proteins are degraded,they are particularly ill-suited to time-sensitive studies,such as signal transduction,that occur on the milliseconds to hours time scale.28Chemical genetics and classical genetics are techiniques that compliment each other well.31One of the greatest advantages of classical genetics is the incredible specificity of a gene knockout.While some chemical ligands can be very specific switches with specificity approaching that of a gene knockout,1,3,32the low specificity of other ligands often give “off-target”effects in which the probe may interact with proteins other than the protein(s)targeted.This makes defining specific protein functions very difficult since these off-target effects may lead to toxicity or false or unwanted positive/negative biological results.Not only often lacking in specificity,chemical genetics cannot yet match the generality of genetics.Geneticists can,in theory,“knockout”any gene as long as the genome sequencing is done in the given species,an ability that at this point exists as nothing more than a dream of the chemical geneticist.27These situations are the perfect place for the integration of chemical and classical genetics.28Importantly,unlike drug development where specificity is tantamount,in chemical genetics it does not need to be completely specific,so long as it gives an identifiable phenotype that allows for the deciphering of the target protein’s function and its side effect are relatively small.12Whereas one may desire compounds with affinity in the (sub)nanomolar range capable of producing the desired effect,in reality,compounds of low micromolar affinities are often accepted as good to reasonable candidates in chemicalFigure 2.Forward chemical genetics:A library of compounds is designed,synthesized,or isolated from natural sources mimicking random genetic mutation.The compounds are screened in high-throughput in vivo assays.A desired phenotypic change is then sought,and the compound responsible is considered a “hit”and selected out of the library.The molecule is then typically used as a “hook”to “fish-out”the protein of interest.The protein’s function and the gene responsible for it are then studied.Reverse chemical genetics:A purified protein is selected and screened in vitro against a library of compounds to identify a specific binding ligand.That selected ligand is then introduced to an in vivo system to determine the protein’s role by monitoring phenotypic changes.2478Chemical Reviews,2006,Vol.106,No.6Walsh andChanggenetics.11Despite this,and with an understanding of the necessary medicinal chemistry follow-up modifications and studies required,chemical genetics still has the advantage of immediately offering a potential drug lead,rather than simply a target gene or protein,as in classical genetics.13,29,33Interestingly,a lead compound developed in drug discovery that may not possess pharmacokinetic properties suitable for a therapeutic purpose may still be used as a probe in chemical genetics studies.24In fact,the lower pharmacokinetic property requirements for chemical genetics probes compared to drugs allows for the use of a greater variety of functional groups and a maximization of the chemical space in library constituents.34This review provides a survey of contemporary research in chemical genetics with a special emphasis on the techniques and methods in use.Studies where small mol-ecules,in concert with genomic techniques,are used to study genome-wide effects (chemical genomics)or work highly focused on pharmaceutical development through the integra-tion of chemistry,genomics,target family design,and chemo/bio-informatics (chemogenomics)will not be thoroughly covered in this review,except where aspects of the work are relevant to or integrate chemical genetics.3,14,27,35-522.Chemical ToolboxesChemical genetics is dependent on the integration of techniques spanning many disciplines including combina-torial chemistry and high-throughput screening (HTS).Col-lections of compounds,so-called libraries,are the absolute starting point for any chemical genetics study or discussion.Here,highlights of chemical tools relevant to chemical genetics will be discussed,while leaving out the full details of library generation itself,which has already been the subject of many reviews.53-612.1.Natural ProductsNature does not lack for time,and over time many powerfully bioactive compounds have evolved.For example,colchicine has been used as a drug for over 2000years.It is generally accepted that collections of natural products have a higher probability of delivering hits than a typical synthetic combinatorial library.3,62Natural products are obtained from sources such as plants,soil,and marine sponges.3Most difficult in this natural product discovery is isolating any active components out of the whole mixture extract.The typical and time-consuming isolation route is known as bioassay-guided purification.9,63,64Purification involves iterative processes where compounds undergo multiple rounds of extraction and chromatography guided by the screening results of the successive crude extracts.These studies are hampered by overlooking poten-tially highly active low-abundance compounds,the cytotox-icity of one component masking the desired effect of another component,and bioactivity resulting from complicated synergistic effects.9,63,64In addition,determining the structure of the compound is another laborious and challenging task.Over the past decade and a half,these drawbacks led to a retreat from natural products by the majority of the major pharmaceutical companies,but the disappointment in the number of drugs arising from combinatorial chemistry and the continued benefits and development of natural products (see mevinolin and cyclosporine)are luring many back to them.64-68Currently,major pharmaceutical companies are re-embracing natural products and natural product libraries.Natural products need not have their use restricted to therapeutics;they can also be of great value to chemical genetics studies.Extremely exciting is the integration of traditional natural products and their scaffolds with modern combinatorial and HTS tools.65,69,70Perhaps success will lieFigure 3.Representative natural products used in chemical genetics studies.Chemical Genetics Chemical Reviews,2006,Vol.106,No.62479in a balance of the old and the new.Some representative natural products used in chemical genetics studies are listed in Figure 3.2.2.Natural-Product-Like CompoundsNatural-product-like libraries offer a highly desirable middle ground between those who seek powerfully bioactive compounds from natural libraries and those who seek the ease of synthesis found in libraries composed of small organic molecules.Natural products are typically chiral and extremely complex and contain many stereogenic centers.These structures are often highly potent and serve as attractive leads for drug development.71Natural products can be considered privileged structures in a biological context and an excellent starting point for library design with a high probability for biological activity.62,72In Waldmann’s terms,natural products,based on their evolutionary selection,serve as “biologically validated”starting points for library design.73These compounds often contain sets of related and homolo-gous pharmacophoric groups throughout families of natural compounds.74Natural-product-like libraries are those col-lections of compounds whose structures are based on or share high structural homology with natural products.69These libraries may be designed to generate derivatives of a natural product scaffold,as Nicolau et al.did in their diverse synthesis of benzopyran derivatives 75-77or as Schreiber et al.did in their modification of a natural product scaffold,(-)-shikimic acid,to a highly diversified tetracyclic template/scaffold.64,78In addition,some have sought to generate natural-product-like libraries not to improve on known activity but to expand a molecule’s functionality into a previously unknown areas of biological space.79The syn-thesis of natural-product-like libraries encounters many ofthe difficulties of synthesizing natural products,along with the challenge of synthesizing these complex structures on the solid phase.69,71A great deal of work has been produced,and detailed studies of scaffold design and natural-product-like libraries are well documented in the literature.69,72,80,81Figure 4provides some representative structures of members of natural-product-like libraries.69,72,82,832.3.Diversity Oriented SynthesisAfter the combinatorial boom of the 1990s,a well-documented disappointment in the number of quality leads has set in.65The compounds coming out of early combina-torial libraries simply did not perform up to the designer’s expectations.Guidelines such as Lipinski’s rules are helpful for generating more drug-like small molecules,but it has been argued that compounds from solid phase organic synthesis may not be chemically diverse enough to generate the desired selectivity and potency.84,85For example,a library of thousands or millions of compounds from a traditional combinatorial library may populate only a small area of chemical space.62,84,86Diversity oriented synthesis (DOS)is a new term for a method of library construction in chemical genetics.It is also attracting attention in drug discovery for its great potential in generating valuable lead discoveries.87Advocates of the DOS approach point to the archetypal case of a flat aromatic or heterocyclic core dotted with various diverse appendages that has largely failed to deliver the promised drugs.In addition,the very basis of a structure -activity relationship (SAR)study is the intuitive notion that structurally similar compounds yield biologically similar profiles.Therefore,combinatorial libraries of little structural diversity will occupy a narrow window of biological space,thus limiting theirFigure 4.Representative natural-product-like compound structures.2480Chemical Reviews,2006,Vol.106,No.6Walsh andChangbroad applicability.The compounds generated from tradi-tional combinatorial chemistry,with their absence of multiple if any stereocenters and their limited functional group variety, do not occupy the chemical space required.3,62,74,84The discrepancy between the success of natural products, especially in terms of selectivity and potency,and the as yet disappointing rate of lead generation from traditional combinatorial libraries has forced the question of whether natural products occupy regions of chemical space evolu-tionarily fine-tuned to be the most potent and active compounds.88Thus,one of the stated goals of DOS is to create extremely diverse libraries populating the maximum amount of chemical space to explore the greatest amount of biological space.DOS is a modern development but has evolved from traditional solid-phase synthesis and particularly draws upon the split-pool/one-bead-one-compound approach.89Schreiber et al.have done significant work in developing DOS and optimizing methodologies to shuttle these compounds sys-tematically through the various phases of chemical genetics studies.90,91It draws its name from its contrast to thetraditionally used approach of target oriented synthesis (TOS).Beginning with a known target(often a natural product),TOS uses retrosynthetic analysis to work backward from a complicated product to simple and available starting materials.The goal of TOS is to get to a precise region of chemical space s a solo target or a few closely related derivatives.Retrosynthetic analysis is not applicable to DOS since no target structure is available and thus the library cannot be targeted.Therefore,new thinking and planning strategies are required,and the idea of forward synthetic analysis has been proposed that moves in the direction of simple to complex, or reactants to products,in contrast to TOS.DOS strategies focus on maximizing diversity by utilizing branched and divergent pathways where the products of one reaction are common substrates for the next and where any follow-up chemistry must be efficient and systematic.92,93DOS’s ability to generate nature-mimicking diversity from simple building blocks is one of its most desirable features.92Structural diversity is obtained by varying the building blocks and functional groups,diverse stereochemistry,and last and most interestingly,diversity generated in the compounds chemical skeletons/scaffold from a common framework.Molecules that occupy a greater degree of3-D space or those that are more globular/spherical are a popular goal of DOS,as opposed to the relatively flat or circular molecules tradition-ally used in combinatorial chemistry.88DOS places a huge strain on synthetic planners since their proposed chemistry must be general,applicable,and compatible with all the various functional groups present in the library at any time.94 Therefore,the reaction or process is the key to forward synthetic planning,since common reactivities are essential among library intermediates.88Early DOS strategies used a one-synthesis/one-skeleton approach.This involved attaching numerous appendages to the molecular framework.The powerful effect of diverse stereochemisty on biological activity is well-known and has been a major focus in DOS.This was key to the design of some highly diverse and populated libraries(Figure5).95The most promising and intriguing approach,however,is the ability to produce skeletal diversity from one common scaffold.72,88Within this concept,the predominant goal is to achieve structural diversity combinatorially.93,96Schreiber et al.have sought to generalize the DOS method and describe two ways to diversify the scaffold(Figure6). The first process,differentiation,uses different reagents to generate different scaffolds.The second process takes advantage of so-calledσelements.Schreiber describes these σelements as pre-encoding skeletal information into a collection of products having distinct molecular skeletons using common reaction conditions.These are called“folding”processes due to their likeness to protein folding,in that abundant structural information is encoded by primary amino acid sequences that produce3-D macromolecules in common folding buffers.88Figure7illustrates how a branching differentiation pathway in DOS give rise to skeletal diversity through consecutive Diels-Alders reactions.Figure8il-lustrates the concept ofσelements.Wong and co-workers have also exploited DOS libraries incorporating interesting scaffolds such as iminocyclitols to identify selective R-fucosidase inhibitors and N-acetyl- -hexosaminidase inhibitors targeting osteoarthritis.97,98DOS combined with in situ microtiter plate screening has also provided sulfotransferase and HIV protease inhibitors99-101 Numerous research reports and reviews of DOS libraries have been published.72,80,87-90,92-96,102-113Figure5.Two million compounds synthesized from30alkynes, 62amines,and62carboxylic acids.The first structure includes three resin spacers,both enantiomers,and ortho-,meta-,and para-iodo benzyls.Figure6.Skeletal diversity pathways:(a)differentiating processes, and(b)folding processes.Figure7.Representative example of differentiation DOS pathways leading to skeletal diversity.Chemical Genetics Chemical Reviews,2006,Vol.106,No.624812.4.Tagged LibrariesTagged libraries represent unique opportunities in library design.114In this approach,libraries may be synthesized by any means and designed around any type of scaffold but must contain some functional tags integrated into the library.These tags are incorporated into the library compounds from the beginning,and they bestow some additional function into the molecules.The most common example of a tag is a fluorophore,but many more variations exist that allow the compounds to have functions extending beyond their bio-logical activity that may aid in areas such as target identifica-tion or ligand assembly.Peptide nucleic acids (PNA),developed by Buchardt et al.,are oligonucleotide-like molecules that have their DNA backbone removed and replaced with an achiral polyamide backbone that can hybridize with DNA through strand displacement 115PNA tags have been used in the development of tagged libraries that allow for the spatially addressable localization and identification of probes on an oligonucleotide microarray surface (Figure 9).The PNA tag encodes the synthetic history of the probe molecule and also hybridizes with a complimentary cDNA strand on the microarray surface to specifically identify the small molecule based on its location on the array.In early work,Schultz et bined PNA tagged libraries with microarray technology.116,117In one study,cathepsin inhibitors were identified by screening libraries in complex mixtures with the target protein before hybridization to the array.This spatially addressable PNA array also found use in the activity based profiling of proteases with the detection of caspase activation upon apoptosis induction.The characterization of the activated caspase and the inhibition of the caspase that executed the apoptotic phenotype were possible through this technology.Winssinger et al.have continued work in this area by screening a 4000member PNA library targeted to cysteine proteases against dust mite allergen extracts and identified Der p1as a target implicated in dust mite allergies.118Winssinger et al.have also expanded upon the methods to produce PNA libraries through their detailed synthesis of aPNA-encoded cysteine protease inhibitor library.These workers utilized an alternative solid-phase PNA synthesis based on azididopeptide nucleic acids where the azide is a mask for the amino group.119,120Harris et al.have signifi-cantly expanded the use of PNA-encoded microarrays in profiling proteases with rhodamine-based fluorogenic sub-strates through their recent demonstration of a system that allows for the screening of samples that range from single proteases to complex clinical blood samples.121This method utilized fluorogenic protease substrates linked to ing these latent fluorophores instead of substrates linking FRET fluorophores was advantageous since only proteolysis at the residue adjacent to the fluorophore gives a signal,and proteolysis of that bond changes the electronic properties of the fluorophore significantly enough to give rise to a large increase in fluorescence,thus aiding detection.Click chemistry offers unique tags that can be used to generate library members through strategies such as targetFigure 8.Skeletal diversity generating folding process s the transformation of substrates having different σelements into products having different skeletons under a common set of reaction conditions.Figure 9.PNA tagged libraries.2482Chemical Reviews,2006,Vol.106,No.6Walsh andChang。
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a r X i v :a s t r o -p h /0104308v 1 18 A p r 2001Draft version February 1,2008Preprint typeset using L A T E X style emulateapj v.04/03/99CHEMICAL ENRICHMENT AT HIGH REDSHIFTS:UNDERSTANDING THE NATURE OFDAMPED LY αSYSTEMS IN HIERARCHICAL MODELSPatricia B.Tissera1,4Diego mbas2,4Mirta B.Mosconi2Sofia Cora 3,4Draft version February 1,2008ABSTRACT We use cosmological hydrodynamical simulations including star formation and metal enrichment to study the evolution of the chemical properties of galaxy-like objects at high redshift in the range 0.25<z <2.35in a hierarchical clustering scenario.As the galactic objects are assembled we find that their gaseous components exhibit neutral Hydrogen column densities with abundances and scatter comparable to those observed in damped Lyman-αsystems (DLAs).The unweighted mean of abun-dance ratios and least square linear regressions through the simulated DLAs yield intrinsic metallicity evolution for the [Zn/H]and [Fe/H],consistent with results obtained from similar analysis of available observations.Our model statistically reproduces the mild evolution detected in the metallicity of the neutral hydrogen content of the Universe,given by mass-weighted means,if observational constraints are considered (as suggested by Boiss´e e et al.1998).For the α-elements in the simulated DLAs,we find neither enhancement nor dependence on metallicity.Our results support the hypotheses that DLAs trace a variety of galactic objects with different formation histories and that both SNI and SNII are contributing to the chemical enrichment of the gas component at least since z ≈2.This study indicates that DLAs could be understood as the building blocks that merged to form today normal galaxies within a hierarchical clustering scenario.Subject headings:galaxies:formation-evolution -abundances -cosmology:theory -dark matter -methods:numerical 1.INTRODUCTION Studies of DLA absorbers have provided hints on the properties of structure at high redshift,from both kine-matical and chemical points of view (Lu et al.1996;Pet-tini et al.1997;Wolfe et al.1995;Haehnelt,Steinmetz &Rauch 1998;Pettini et al.1999;Prochaska &Wolfe 1999).Analysis of the absorbers at low z show that these sys-tems have diverse morphologies (e.g.,Rao &Briggs 1993;Le Brun et al.1997)while at high z their nature remainsunclear.First kinematical studies suggested that high red-shift DLAs were large disks similar to those in present-dayspiral galaxies (e.g.,Wolfe et al.1995;Prochaska &Wolfe1997).However,Haehnelt et al.(1998)show that they arealso consistent with being the building blocks of local typi-cal galaxies,as predicted by hierarchical clustering scenar-ios (HCSs).The metallicity properties of DLAs supportthe idea that they are chemically young objects (e.g.,Pet-tini et al.1999,Prochaska et al.2000).However,the de-pendence of their metallicities on z is a controversial pointsince,until recently,only very weak or non-evolution atall has been reported from the analysis of the mean metal-licity of the neutral hydrogen with the abundance ratiosweighted by the HI column density (N HI )(Prochaska &Wolfe 2000;Pettini et al.1999;Vladilo et al.2000)in con-trast with some theoretical models which predict substan-tial evolution of the neutral hydrogen abundances (e.g.,Edmunds &Phillips 1997;Pei et al.1999;see Cen &Os-triker 1999for a different result).However,the unweighted mean metallicities and linear regressions through the in-dividual data show stronger evolution signals as reported in recent works (i.e.,Prochaska &Wolfe 2000;Vladilo et al.2000;Hou et al.2001).Detecting evolution in chem-ical abundances of HI gas mass may be difficult due to several biasing factors.Among them,dust depletion and obscuration have been probed to be a source of uncertain-ties for some element measurements (e.g.,Vladilo 1998;Hou et al.2001),while the limited redshift coverage with the known DLAs may not be adequate for detecting the presence of evolution.As first pointed out by Boiss´e et al.(1998),DLAs with high N HI and high metallicity might be missing from the data as a consequence of dust extinction which would imply a biased determination of evolution.For the α−elements,dust-corrected data show mild en-1Institutode Astronom´ıa y F ´ısica del Espacio,Argentina 2Observatorio Astron´o mico de la Universidad Nacional de C´o rdoba,Argentina3Observatorio Astron´o mico de La Plata,Argentina4Consejo Nacional de Investigaciones Cient ´ıficas y T´e cnicas 12Chemical Enrichment at High Redshiftshancement or near solar values for most observed elements in contrast to the metallicity pattern of metal-poor Galac-tic stars(e.g.,Vladilo1998;Pettini et al.2000).This might imply a different SF history than that of the Milky Way,although Prochaska et al.(2000)found an agreement between the properties of the Galactic thick disk and the DLAs.In HCSs,where galaxies are formed by aggregation of smaller substructures,mergers and continuous gas infall play an important role,contributing to regulate the star formation(SF;Tissera2000)and chemical histories(e.g., Cora et al.2000)of the galactic objects.As suggested by Haehnelt et al.(1998)from a kinematical study of numerical simulations,DLAs could be the progenitor sub-structures of today galaxies that merge to form galactic objects in a hierarchical clustering scenario.The variety of morphological types together with the fact that they tend to be chemically young seem to support this hypoth-esis.With the aim at understanding the possible link be-tween the structure in a HCS and the nature of DLAs, in this letter,we assess the chemical properties of today-galaxy building blocks as a function of the redshift.For this purpose,we focus our study on the analysis of the unweighted mean metallicities of the neutral hydrogen as a function of z since they are more sensitive to the prop-erties of the individual objects.We also comment on the mass-weighted mean metallicities that are related to the chemical content of the Universe.We use hydrodynami-cal cosmological models that treat the non-linear evolution of both baryons and dark matter in a self-consistent way, providing a well-described history of formation,and in-clude star formation and chemical evolution.Results of the simulations are compared with available observational data on chemical abundances of DLAs.We discuss impli-cations for galaxy formation.2.CHEMICAL PROPERTIES OF GALACTIC OBJECTS Our hydrodynamical chemical simulations follow the joint evolution of the dark matter and baryons within a cosmological context(Tissera et al.1997)including SF and chemical evolution.Stars are formed from cold and dense gas in a convergentflow according to the Schmidt law.Gaseous particles are gradually transformed into stars in different SF episodes.The contribution of type I(SNI)and type II(SNII)supernovas from each of these SF episodes to the chemical enrichment of the gas compo-nent are taken into account according to stellar evolution models and metallicity enrichment yields.Chemical ele-ments generated in a given particle are distributed among gas particles within its neighboring area,weighting each contribution with a kernel function that depends on the distance(i.e.,by using the smooth particle hydrodynam-ics technique).We adopt the yields given by Woosley&Weaver(1995) for SNII and those given by Thielemann,Nomoto& Hashimoto(1993)for SNI.A time delay of108yrs is as-sumed for binary star systems to explode as SNI.We adopt afixed Salpeter Initial Mass Function with lower and up-per mass cut-offs of0.1M⊙and120M⊙,respectively. In this work the effects of energy injection into the inter-stellar medium due to supernova explosions have not been included.For a detailed discussion of the chemical model see Mosconi et al.(2000).We analyze cosmological simulations of a typical10 Mpc cube volume represented by643equal mass particles (Ωb=0.1).Initial conditions are consistent with a Stan-dard Cold Dark Matter Universe(H=50km s−1Mpc−1) with cluster abundance normalization,σ8=0.67.We have run a set of three simulations with different realizations of the power spectrum,estimating averaged results over them.The SN parameters adopted in these simulations correspond to those giving the best agreement with obser-vations of galaxies at z=0(Mosconi et al.2000)and the [O/Fe]abundance pattern in the Milky Way(Cora et al. 2000).We identified galactic objects at their virial radius at dif-ferent stages of evolution of the simulated volume.Galac-tic objects are formed by a dark matter halo and a bary-onic component in the form of gas and stars.To dimin-ish numerical resolution problems,we analyze galactic ob-jects with more than200baryonic particles within their virial radius and in the range0.25<z<2.35.Conse-quently,the analyzed objects have virial velocities within ≈100−250km s−1.We study a total number of380 galactic objects satisfying the above conditions which are all considered as possible absorbers.It is likely that DLAs observations map the chemi-cal properties of the gaseous disks not expected to be good tracers of the metal content at the central regions (e.g.,Jimenez et al.1999;Somerville et al.2001; Savaglio2000).Hence,in order to carry out a suit-able comparison between the simulated galactic objects and DLAs observations,we use a Monte Carlo technique to simulate line-of-sights(LOS)and estimate the chem-ical properties of the neutral hydrogen component with N HI>2×1020atoms/cm−2(Wolfe et al.1986)along the LOS.We assume that the hydrogen mass in a gas particle remains neutral if no SF activity has ever occured within that particle.As a combined result of dynamical evolution,mergers and interactions,the SF rate history of each galactic ob-ject can be described as a contribution of an ambient SF rate and a series of starbursts(e.g.,Tissera2000).The timings between starbursts are not ad hoc,but given nat-urally by the evolution of the objects in the HCS adopted. Thus,we have a consistent description of the chemical en-richment of the stellar populations and gaseous component due to the fact that the different ejecta times of SNI and SNII can be properly taken into account.Note that the simulated sample is not affected by dust depletion or ob-scuration.These facts make our simulations powerful tools to explore the nature of DLAs.For each galactic object selected at a given redshift we define the HI mass-weighted mean of abundance ratio of elements K and J,[K/J]in the column of HI along a LOS, as:Tissera et al.3[K/J]=log n pi=1K i M gasi4Chemical Enrichment at High Redshifts we obtained an evolution signal of0.46±0.10while theweighted ratios show a weaker change consistent with mildevolution:0.24±0.12.Clearly,selection biases could havestrong implications when estimating changes with redshift.The standard dispersions shown in Figure1for both el-ements in the simulated sample reproduce fairly well theobserved dispersions of DLAs:for the[Zn/H]the buildingblocks show a dispersion ofσzlow =0.68andσzinter=0.78while observations haveσzlow =0.42andσzinter=0.86.The simulated[Fe/H]ratios haveσzlow =0.60andσzinter=0.77compared to the observed ones ofσzlow =0.45andσzinter=1.24.In our models this dispersion arises as the results of the variety of galactic objects with diverse evo-lutionary histories:merger tree,star formation,chemical enrichment,etc.,at different z,supporting a similar origin for the large dispersion observed in DLAs.We estimate the unweighted mean[Si/Fe]and[S/Fe]ra-tios in order to analyze the behavior of theα-elements in the HI gas mass of the simulated galactic objects.¿From Figure2a we can appreciate that the mean[Si/Fe]ratios have nearly solar values and show no dependence on metal-licity,consistent with the dust-corrected observations re-ported by Vladilo(1998)and Pettini et al.(2000)who assumed that Zn is undepleted and traces Fe.A similar behavior was found for mean[S/Fe]ratios.In Figure2b we show the unweighted<[Zn/Fe]>abun-dances versus<[Fe/H]>.Wefind that the HI compo-nent of the simulated DLAs tend to exhibit[Zn/Fe]values around a mean of0.27±0.28(1σdeviation).It should be noted that these values are consistent with the observed range for DLAs with no dust corrections(with a mean of0.47±0.31)while dust-corrected ratios show nearly solar values.As more extensively discussed by Prantzos &Boissier(2000;see also Lu et al.1996and Prochaska &Wolfe2000)current nucleosynthesis models of the zinc have problem in reproducing the observed abundance pat-tern of the Milky-Way.If we had assumed that Zn traces Fe for all metallicites(e.g.,Pettini et al.2000),our models would have produced mean ratios in agreement with those of Vladilo(1998)corrected by dust-depletion.3.DISCUSSION AND CONCLUSIONS Observational studies of the chemical properties of DLAs have provided unvaluable information on galaxy evolution up to z≈4.This letter aims to provide a theoretical frame to understand these observations within HCSs.The chemical hydrodynamical cosmological models analyzed take into account different physical mechanisms controlling the formation and evolution of galaxies:grav-itational collapse,tidal torques,mergers,interactions,gas infall,gradient pressure,radiative cooling,SF and chem-ical enrichment by SNI and SNII explosions.In this sce-nario we follow the formation and evolution of galaxy-like objects,analyzing the chemical properties of the different substructures that merge hierarchically.In order to properly compare the galactic objects in the simulations with the observed DLAs,we estimated the abundances of HI along LOS randomly distributed.We found that the simulated galactic objects have gaseous components that,when randomly sampled,have[Zn/H] and[Fe/H]abundances within the observed range for DLAs.In the simulations,the unweighted[Zn/H]and [Fe/H]ratios show evolution with z in statistical agree-ment with results obtained from similar analysis of the available observations(see also Vladilo et al.2000; Prochaska&Wolfe2000;Hou et al.2001).However, the mass-weighted metallicities of the simulated and ob-served N HI show opposite trends;while the former show evolution,the later do not.Part of this discrepancy can be attributed to observational biases that might prevent low-density metal-poor and very metal-rich and dense zones to be detected by current observations.In fact,taking into account these effects by applying afilter to the simulated [Zn/H],we found,on one hand,that the unweighted means still show a clear evolution,and,on the other,that the filtered weighted abundances yield a weaker dependence with z in agreement with corresponding observations(e.g., Pettini et al.1999).Accordingly to our results,this obser-vational bias seems to affect more strongly the weighted means suggesting that the interpretation of the evolution of the chemical content of the Universe by using DLAs should be taken with extra caution.More observations, principally of high density and high metallicity HI column densities,are needed to draw afinal conclusion.The lack ofα−enhancements in the mean abundances of simulated galactic objects shows that,in the redshift range analyzed,there are already significant contributions from both types of SNs,so that the mean unweighted metallic-ities of the N HI are nearly solar,in agreement with DLAs observations after dust corrections.We detect no evolution of[α/Fe]with metallicity implying that,for our galactic objects,their SF histories are the result of the superpo-sition of different starbursts occuring at different epochs. Moreover,the starbursts could have been triggered in dif-ferent substructures that merge to form the galactic ob-jects analyzed at a given z.In the case of Zn we found enhancement with respect to the Fe but no dependence on metallicity.A lower Zn nucleosynthesis production in the models(or assuming that Zn traces Fe)would have pro-duced[Zn/Fe]values in agreement with the dust-corrected observed DLAs(Vladilo1998).This lower Zn production does not affect the agreement found between the observed and simulated[Zn/H]at low z shown in Figure1a.At high z,models and observations can be reconciled if one takes into account that several high z estimations of[Zn/H]in observed DLAs are upper limits instead of accurate values. The zinc remains a controversial element as pointed out by several authors(Lu et al.1996;Pettini et al.1999;Pet-tini et al.2000;Prantzos&Bossier2000;Savaglio2000) whose production and evolution are not fully understood. To sum up,the chemical properties of galactic objects in our models at a given z are the result of their past evolu-tion:collapse,mergers,interactions,SF history,etc.Since we do not impose any particular constraint to select the galactic objects in the models,the results of our chemical analysis seem to support that DLAs could be the build-Tissera et al.5ing blocks of today normal galaxies within a hierarchical context.We thank the anonymous Referee for a careful reading and thoughtful comments that helped to improve this let-ter.This work was partially supported by the Consejo Na-cional de Investigaciones Cient´ıficas y T´e cnicas,Agencia de Promoci´o n de Ciencia y Tecnolog´ıa,Fundaci´o n Antor-chas and Secretaria de Ciencia y T´e cnica de la Universidad Nacional de C´o rdoba.P.Tissera thanks the hospitality of Observatorio Astron´o mico de C´o rdoba during her visits.REFERENCESBoiss´e,P.,Le Brun,V.,Bergeron,J.,&Deharverng,J.M.1998, A&A,333,841Cen,R.,&Ostriker,J.P.1999,ApJ,519,L109Cora,S.A.,Mosconi,M.B.,Tissera,P.B.,&Lambas,D.G.2000, Proceeding of Stars,Gas and Dust in Galaxies:Exploring the Links (astro-ph/0007072)Edmunds,M.G.&Phillips,S.1997,MNRAS,292,733 Haehnelt,M.G.,Steinmetz,M.,&Rauch,M.1998,ApJ,495,647 Hou,J.L.,Boissier,S.,&Prantzos,N.2001,A&A,in press(astro-ph/0102188)Jimenez,R.,Bowen,D.V.,&Matteucci,F.1999,ApJ,514,L83 Le Brun,V.,Bergeron,J.,Boiss´e,P.,&Deharveng,J.M.1997,A&A, 279,733Lu,L.,Sargent,W.L.W.,Barlow,T.A.,Churchill,C.W.,&Vogt, S.S.1996,ApJS,107,475Mosconi,M.B.,Tissera,P.B.,Lambas,D.G.,&Cora,S.A.2000, MNRAS,in press(astro-ph/0007074)Pei,Y.C.,Fall,S.M.,&Hauser,M.G.1999,ApJ,522,604 Pettini,M.,Smith,L.,King,D.,&Hunstead,R.1997,ApJ,486,665 Pettini,M.,Ellison,S.L.,Steidel,C.C.,&Bowen,D.V.1999,ApJ, 510,576Pettini,M.,Ellison,S.L.,Steidel,C.C.,Shapley,A.E.,&Bowen, D.V.2000,ApJ,532,65Prantzos,N.,&Boissier,S.2000,MNRAS,315,82Prochaska,J.X.,&Wolfe,A.M.1997,ApJ,487,73Prochaska,J.X.,&Wolfe,A.M.1999,ApJS,121,369 Prochaska,J.X.,&Wolfe,A.M.2000,ApJ,533,L5 Prochaska,J.X.,Naumov,S.O.,Carney,B.W.,McWilliam,A.,& Wolfe,A.M.2000,AJ,12,2513Rao,S.M.,&Briggs,F.H.1993,ApJ,419,515Savaglio,S.2000,Harwit,M.,Hauser,M.,eds.,The Extragalactic Infrared Background and its Cosmological Implications,IAU,vol. 204(astro-ph/0011473)Somerville,R.S.,Primack,J.R.,&Faber,S.M.2001,MNRAS, 320,504.Thielemann,F.K.,Nomoto,K.,&Hashimoto,M.1993,Prantzos, N.,Vangoni-Flam,E.,Cass´e N.,eds.,Origin and Evolution of the Elements,p.299Tissera,P.B.2000,ApJ,534,636Tissera,P.B.,Lambas,D.G.,&Abadi,M.G.1997,MNRAS,286,384 Vladilo,G.1998,ApJ,493,583Vladilo,G.,Bonifacio,P.,Centurion,M.,&Molaro,P.2000,ApJ, 543,24Wolfe,A.M.,Turnshek,D.A.,Smith,H.E.,Cohen,R.D.,1986, ApJS,61,249Wolfe,A.M.,Lanzetta,K.M.,Foltz,C.B.,&Chaffee,F.,J.1995, ApJ,454,698Woosley,S.E.,&Weaver,T.A.1995,ApJS,101,1816Chemical Enrichment at High RedshiftsFig.1.—[Zn/H](a)and[Fe/H](b)unweighted mean abundances for the neutral hydrogen along LOS in the galactic objects in the three simulations as a function of the redshift(filled circles).Error bars correspond to1σstandard deviation.We include observational data(open pentagons)for DLAs taken from Lu et al.(1996),Pettini et al.(1997;1999;2000),Vladilo(1998)and Prochaska&Wolfe(1999;2000).The downward-(upward-)pointing arrows indicate upper(lower)limits of[Zn/H].Unweighted mean values for the simulated DLAs(dotted-open circles)and the observations(dotted-open pentagons)in the low and intermediate redshift intervals are also plotted.These symbols are superimposed in the intermediate redshift interval in Figure(a).Solid lines are the least square linear regression for the whole sample of simulated DLAs.Fig. 2.—[Si/Fe](a)and[Zn/Fe](b)unweighted mean abundances for neutral hydrogen along LOS in the simulated DLAs in the three simulations for each redshift analyzed as a function of the metallicity[Fe/H](filled circles).Error bars correspond to1σstandard deviation. We include observational data for DLAs without dust corrections(open pentagons)taken from Lu et al.(1996)and Prochaska&Wolfe (1999);dust corrected values(dotted-open pentagons)are obtained from Vladilo(1998)and Pettini et al.(2000).The downward-(upward-) pointing arrows indicate upper(lower)limits of[Si/Fe]and[Zn/Fe].。