Extension Properties of Meromorphic Mappings with Values in Non-Kahler Manifolds

合集下载

ASTM D 790-2007(弯曲)

ASTM D 790-2007(弯曲)

Designation:D790–07Standard Test Methods forFlexural Properties of Unreinforced and Reinforced Plastics and Electrical Insulating Materials1This standard is issued under thefixed designation D790;the number immediately following the designation indicates the year of original adoption or,in the case of revision,the year of last revision.A number in parentheses indicates the year of last reapproval.A superscript epsilon(e)indicates an editorial change since the last revision or reapproval.This standard has been approved for use by agencies of the Department of Defense.1.Scope*1.1These test methods cover the determination offlexural properties of unreinforced and reinforced plastics,including high-modulus composites and electrical insulating materials in the form of rectangular bars molded directly or cut from sheets, plates,or molded shapes.These test methods are generally applicable to both rigid and semirigid materials.However,flexural strength cannot be determined for those materials that do not break or that do not fail in the outer surface of the test specimen within the5.0%strain limit of these test methods. These test methods utilize a three-point loading system applied to a simply supported beam.A four-point loading system method can be found in Test Method D6272.1.1.1Procedure A,designed principally for materials that break at comparatively small deflections.1.1.2Procedure B,designed particularly for those materials that undergo large deflections during testing.1.1.3Procedure A shall be used for measurement offlexural properties,particularlyflexural modulus,unless the material specification states otherwise.Procedure B may be used for measurement offlexural strength only.Tangent modulus data obtained by Procedure A tends to exhibit lower standard deviations than comparable data obtained by means of Proce-dure B.1.2Comparative tests may be run in accordance with either procedure,provided that the procedure is found satisfactory for the material being tested.1.3The values stated in SI units are to be regarded as the standard.The values provided in brackets are for information only.1.4This standard does not purport to address all of the safety concerns,if any,associated with its use.It is the responsibility of the user of this standard to establish appro-priate safety and health practices and determine the applica-bility of regulatory limitations prior to use.N OTE1—These test methods are not technically equivalent to ISO178.2.Referenced Documents2.1ASTM Standards:2D618Practice for Conditioning Plastics for TestingD638Test Method for Tensile Properties of PlasticsD883Terminology Relating to PlasticsD4000Classification System for Specifying Plastic Mate-rialsD4101Specification for Polypropylene Injection and Ex-trusion MaterialsD5947Test Methods for Physical Dimensions of Solid Plastics SpecimensD6272Test Method for Flexural Properties of Unrein-forced and Reinforced Plastics and Electrical Insulating Materials by Four-Point BendingE4Practices for Force Verification of Testing Machines E691Practice for Conducting an Interlaboratory Study to Determine the Precision of a Test Method2.2ISO Standard:3ISO178Plastics—Determination of Flexural Properties of Rigid Plastics3.Terminology3.1Definitions—Definitions of terms applying to these test methods appear in Terminology D883and Annex A1of Test Method D638.4.Summary of Test Method4.1A bar of rectangular cross section rests on two supports and is loaded by means of a loading nose midway between the supports.A support span-to-depth ratio of16:1shall be used unless there is reason to suspect that a larger span-to-depth ratio may be required,as may be the case for certain laminated materials(see Section7and Note7for guidance).1These test methods are under the jurisdiction of ASTM Committee D20on Plastics and are the direct responsibility of Subcommittee D20.10on Mechanical Properties.Current edition approved Sept.1,2007.Published October2007.Originally approved st previous edition approved in2003as D790–03.2For referenced ASTM standards,visit the ASTM website,,or contact ASTM Customer Service at service@.For Annual Book of ASTM Standards volume information,refer to the standard’s Document Summary page on the ASTM website.3Available from American National Standards Institute(ANSI),25W.43rd St., 4th Floor,New York,NY10036,.*A Summary of Changes section appears at the end of this standard. Copyright©ASTM International,100Barr Harbor Drive,PO Box C700,West Conshohocken,PA19428-2959,United States.4.2The specimen is deflected until rupture occurs in the outer surface of the test specimen or until a maximum strain (see 12.7)of5.0%is reached,whichever occurs first.4.3Procedure A employs a strain rate of 0.01mm/mm/min [0.01in./in./min]and is the preferred procedure for this test method,while Procedure B employs a strain rate of 0.10mm/mm/min [0.10in./in./min].5.Significance and Use5.1Flexural properties as determined by these test methods are especially useful for quality control and specification purposes.5.2Materials that do not fail by the maximum strain allowed under these test methods (3-point bend)may be more suited to a 4-point bend test.The basic difference between the two test methods is in the location of the maximum bending moment and maximum axial fiber stresses.The maximum axial fiber stresses occur on a line under the loading nose in 3-point bending and over the area between the loading noses in 4-point bending.5.3Flexural properties may vary with specimen depth,temperature,atmospheric conditions,and the difference in rate of straining as specified in Procedures A and B (see also Note 7).5.4Before proceeding with these test methods,reference should be made to the ASTM specification of the material being tested.Any test specimen preparation,conditioning,dimensions,or testing parameters,or combination thereof,covered in the ASTM material specification shall take prece-dence over those mentioned in these test methods.Table 1in Classification System D 4000lists the ASTM material speci-fications that currently exist for plastics.6.Apparatus6.1Testing Machine —A properly calibrated testing ma-chine that can be operated at constant rates of crosshead motion over the range indicated,and in which the error in the load measuring system shall not exceed 61%of the maximum load expected to be measured.It shall be equipped with a deflection measuring device.The stiffness of the testing machine shall be such that the total elastic deformation of the system does not exceed 1%of the total deflection of the test specimen duringtesting,or appropriate corrections shall be made.The load indicating mechanism shall be essentially free from inertial lag at the crosshead rate used.The accuracy of the testing machine shall be verified in accordance with Practices E 4.6.2Loading Noses and Supports —The loading nose and supports shall have cylindrical surfaces.The default radii of the loading nose and supports shall be 5.060.1mm [0.19760.004in.]unless otherwise specified in an ASTM material specification or as agreed upon between the interested parties.When the use of an ASTM material specification,or an agreed upon modification,results in a change to the radii of the loading nose and supports,the results shall be clearly identified as being obtained from a modified version of this test method and shall include the specification (when available)from which the modification was specified,for example,Test Method D 790in accordance with Specification D 4101.6.2.1Other Radii for Loading Noses and Supports —When other than default loading noses and supports are used,in order to avoid excessive indentation,or failure due to stress concen-tration directly under the loading nose,they must comply with the following requirements:they shall have a minimum radius of 3.2mm [1⁄8in.]for all specimens.For specimens 3.2mm or greater in depth,the radius of the supports may be up to 1.6times the specimen depth.They shall be this large if significant indentation or compressive failure occurs.The arc of the loading nose in contact with the specimen shall be sufficiently large to prevent contact of the specimen with the sides of the nose.The maximum radius of the loading nose shall be no more than four times the specimen depth.6.3Micrometers —Suitable micrometers for measuring the width and thickness of the test specimen to an incremental discrimination of at least 0.025mm [0.001in.]should be used.All width and thickness measurements of rigid and semirigid plastics may be measured with a hand micrometer with ratchet.A suitable instrument for measuring the thickness of nonrigid test specimens shall have:a contact measuring pressure of 2562.5kPa [3.660.36psi],a movable circular contact foot 6.3560.025mm [0.25060.001in.]in diameter and a lower fixed anvil large enough to extend beyond the contact foot in all directions and being parallel to the contact foot within 0.005mm [0.002in.]over the entire foot area.Flatness of foot and anvil shall conform to the portion of the Calibration section of Test Methods D 5947.7.Test Specimens7.1The specimens may be cut from sheets,plates,or molded shapes,or may be molded to the desired finished dimensions.The actual dimensions used in Section 4.2,Cal-culation,shall be measured in accordance with Test Methods D 5947.N OTE 2—Any necessary polishing of specimens shall be done only in the lengthwise direction of the specimen.7.2Sheet Materials (Except Laminated Thermosetting Ma-terials and Certain Materials Used for Electrical Insulation,Including Vulcanized Fiber and Glass Bonded Mica):7.2.1Materials 1.6mm [1⁄16in.]or Greater in Thickness —For flatwise tests,the depth of the specimen shall be the thickness of the material.For edgewise tests,the width of theTABLE 1Flexural StrengthMaterial Mean,103psiValues Expressed in Units of %of 103psi V r A V R B r C R D ABS9.99 1.59 6.05 4.4417.2DAP thermoset 14.3 6.58 6.5818.618.6Cast acrylic 16.3 1.6711.3 4.7332.0GR polyester19.5 1.43 2.14 4.05 6.08GR polycarbonate 21.0 5.16 6.0514.617.1SMC26.04.767.1913.520.4AV r =within-laboratory coefficient of variation for the indicated material.It is obtained by first pooling the within-laboratory standard deviations of the test results from all of the participating laboratories:Sr =[[(s 1)2+(s 2)2...+(s n )2]/n]1/2then V r =(S r divided by the overall average for the material)3100.BV r =between-laboratory reproducibility,expressed as the coefficient of varia-tion:S R ={S r 2+S L 2}1/2where S L is the standard deviation of laboratory means.Then:V R =(S R divided by the overall average for the material)3100.Cr =within-laboratory critical interval between two test results =2.83V r .DR =between-laboratory critical interval between two test results =2.83V R.specimen shall be the thickness of the sheet,and the depth shall not exceed the width(see Notes3and4).For all tests,the support span shall be16(tolerance61)times the depth of the beam.Specimen width shall not exceed one fourth of the support span for specimens greater than3.2mm[1⁄8in.]in depth.Specimens3.2mm or less in depth shall be12.7mm[1⁄2 in.]in width.The specimen shall be long enough to allow for overhanging on each end of at least10%of the support span, but in no case less than6.4mm[1⁄4in.]on each end.Overhang shall be sufficient to prevent the specimen from slipping through the supports.N OTE3—Whenever possible,the original surface of the sheet shall be unaltered.However,where testing machine limitations make it impossible to follow the above criterion on the unaltered sheet,one or both surfaces shall be machined to provide the desired dimensions,and the location of the specimens with reference to the total depth shall be noted.The value obtained on specimens with machined surfaces may differ from those obtained on specimens with original surfaces.Consequently,any specifi-cations forflexural properties on thicker sheets must state whether the original surfaces are to be retained or not.When only one surface was machined,it must be stated whether the machined surface was on the tension or compression side of the beam.N OTE4—Edgewise tests are not applicable for sheets that are so thin that specimens meeting these requirements cannot be cut.If specimen depth exceeds the width,buckling may occur.7.2.2Materials Less than1.6mm[1⁄16in.]in Thickness—The specimen shall be50.8mm[2in.]long by12.7mm[1⁄2in.] wide,testedflatwise on a25.4-mm[1-in.]support span.N OTE5—Use of the formulas for simple beams cited in these test methods for calculating results presumes that beam width is small in comparison with the support span.Therefore,the formulas do not apply rigorously to these dimensions.N OTE6—Where machine sensitivity is such that specimens of these dimensions cannot be measured,wider specimens or shorter support spans,or both,may be used,provided the support span-to-depth ratio is at least14to1.All dimensions must be stated in the report(see also Note5).7.3Laminated Thermosetting Materials and Sheet and Plate Materials Used for Electrical Insulation,Including Vulcanized Fiber and Glass-Bonded Mica—For paper-base and fabric-base grades over25.4mm[1in.]in nominal thickness,the specimens shall be machined on both surfaces to a depth of25.4mm.For glass-base and nylon-base grades, specimens over12.7mm[1⁄2in.]in nominal depth shall be machined on both surfaces to a depth of12.7mm.The support span-to-depth ratio shall be chosen such that failures occur in the outerfibers of the specimens,due only to the bending moment(see Note7).Therefore,a ratio larger than16:1may be necessary(32:1or40:1are recommended).When laminated materials exhibit low compressive strength perpendicular to the laminations,they shall be loaded with a large radius loading nose(up to four times the specimen depth to prevent premature damage to the outerfibers.7.4Molding Materials(Thermoplastics and Thermosets)—The recommended specimen for molding materials is127by 12.7by3.2mm[5by1⁄2by1⁄8in.]testedflatwise on a support span,resulting in a support span-to-depth ratio of16(tolerance 61).Thicker specimens should be avoided if they exhibit significant shrink marks or bubbles when molded.7.5High-Strength Reinforced Composites,Including Highly Orthotropic Laminates—The span-to-depth ratio shall be cho-sen such that failure occurs in the outerfibers of the specimens and is due only to the bending moment(see Note7).A span-to-depth ratio larger than16:1may be necessary(32:1or 40:1are recommended).For some highly anisotropic compos-ites,shear deformation can significantly influence modulus measurements,even at span-to-depth ratios as high as40:1. Hence,for these materials,an increase in the span-to-depth ratio to60:1is recommended to eliminate shear effects when modulus data are required,it should also be noted that the flexural modulus of highly anisotropic laminates is a strong function of ply-stacking sequence and will not necessarily correlate with tensile modulus,which is not stacking-sequence dependent.N OTE7—As a general rule,support span-to-depth ratios of16:1are satisfactory when the ratio of the tensile strength to shear strength is less than8to1,but the support span-to-depth ratio must be increased for composite laminates having relatively low shear strength in the plane of the laminate and relatively high tensile strength parallel to the support span.8.Number of Test Specimens8.1Test at leastfive specimens for each sample in the case of isotropic materials or molded specimens.8.2For each sample of anisotropic material in sheet form, test at leastfive specimens for each of the following conditions. Recommended conditions areflatwise and edgewise tests on specimens cut in lengthwise and crosswise directions of the sheet.For the purposes of this test,“lengthwise”designates the principal axis of anisotropy and shall be interpreted to mean the direction of the sheet known to be stronger inflexure.“Cross-wise”indicates the sheet direction known to be the weaker in flexure and shall be at90°to the lengthwise direction.9.Conditioning9.1Conditioning—Condition the test specimens at236 2°C[73.463.6°F]and5065%relative humidity for not less than40h prior to test in accordance with Procedure A of Practice D618unless otherwise specified by contract or the relevant ASTM material specification.Reference pre-test con-ditioning,to settle disagreements,shall apply tolerances of 61°C[1.8°F]and62%relative humidity.9.2Test Conditions—Conduct the tests at2362°C[73.46 3.6°F]and5065%relative humidity unless otherwise specified by contract or the relevant ASTM material specifica-tion.Reference testing conditions,to settle disagreements, shall apply tolerances of61°C[1.8°F]and62%relative humidity.10.Procedure10.1Procedure A:10.1.1Use an untested specimen for each measurement. Measure the width and depth of the specimen to the nearest 0.03mm[0.001in.]at the center of the support span.For specimens less than2.54mm[0.100in.]in depth,measure the depth to the nearest0.003mm[0.0005in.].These measure-ments shall be made in accordance with Test Methods D5947.10.1.2Determine the support span to be used as described in Section7and set the support span to within1%of the determinedvalue.10.1.3Forflexuralfixtures that have continuously adjust-able spans,measure the span accurately to the nearest0.1mm [0.004in.]for spans less than63mm[2.5in.]and to the nearest 0.3mm[0.012in.]for spans greater than or equal to63mm [2.5in.].Use the actual measured span for all calculations.For flexuralfixtures that havefixed machined span positions,verify the span distance the same as for adjustable spans at each machined position.This distance becomes the span for that position and is used for calculations applicable to all subse-quent tests conducted at that position.See Annex A2for information on the determination of and setting of the span.10.1.4Calculate the rate of crosshead motion as follows and set the machine for the rate of crosshead motion as calculated by Eq1:R5ZL2/6d(1) where:R=rate of crosshead motion,mm[in.]/min,L=support span,mm[in.],d=depth of beam,mm[in.],andZ=rate of straining of the outerfiber,mm/mm/min[in./ in./min].Z shall be equal to0.01.In no case shall the actual crosshead rate differ from that calculated using Eq1,by more than610%.10.1.5Align the loading nose and supports so that the axes of the cylindrical surfaces are parallel and the loading nose is midway between the supports.The parallelism of the apparatus may be checked by means of a plate with parallel grooves into which the loading nose and supports willfit when properly aligned(see A2.3).Center the specimen on the supports,with the long axis of the specimen perpendicular to the loading nose and supports.10.1.6Apply the load to the specimen at the specified crosshead rate,and take simultaneous load-deflection data. Measure deflection either by a gage under the specimen in contact with it at the center of the support span,the gage being mounted stationary relative to the specimen supports,or by measurement of the motion of the loading nose relative to the supports.Load-deflection curves may be plotted to determine theflexural strength,chord or secant modulus or the tangent modulus of elasticity,and the total work as measured by the area under the load-deflection curve.Perform the necessary toe compensation(see Annex A1)to correct for seating and indentation of the specimen and deflections in the machine.10.1.7Terminate the test when the maximum strain in the outer surface of the test specimen has reached0.05mm/mm [in./in.]or at break if break occurs prior to reaching the maximum strain(Notes8and9).The deflection at which this strain will occur may be calculated by letting r equal0.05 mm/mm[in./in.]in Eq2:D5rL2/6d(2) where:D=midspan deflection,mm[in.],r=strain,mm/mm[in./in.],L=support span,mm[in.],andd=depth of beam,mm[in.].N OTE8—For some materials that do not yield or break within the5% strain limit when tested by Procedure A,the increased strain rate allowed by Procedure B(see10.2)may induce the specimen to yield or break,or both,within the required5%strain limit.N OTE9—Beyond5%strain,this test method is not applicable.Some other mechanical property might be more relevant to characterize mate-rials that neither yield nor break by either Procedure A or Procedure B within the5%strain limit(for example,Test Method D638may be considered).10.2Procedure B:10.2.1Use an untested specimen for each measurement.10.2.2Test conditions shall be identical to those described in10.1,except that the rate of straining of the outer surface of the test specimen shall be0.10mm/mm[in./in.]/min.10.2.3If no break has occurred in the specimen by the time the maximum strain in the outer surface of the test specimen has reached0.05mm/mm[in./in.],discontinue the test(see Note9).11.Retests11.1Values for properties at rupture shall not be calculated for any specimen that breaks at some obvious,fortuitousflaw, unless suchflaws constitute a variable being studied.Retests shall be made for any specimen on which values are not calculated.12.Calculation12.1Toe compensation shall be made in accordance with Annex A1unless it can be shown that the toe region of the curve is not due to the take-up of slack,seating of the specimen,or other artifact,but rather is an authentic material response.12.2Flexural Stress(s f)—When a homogeneous elastic material is tested inflexure as a simple beam supported at two points and loaded at the midpoint,the maximum stress in the outer surface of the test specimen occurs at the midpoint.This stress may be calculated for any point on the load-deflection curve by means of the following equation(see Notes10-12):s f53PL/2bd2(3) where:s=stress in the outerfibers at midpoint,MPa[psi],P=load at a given point on the load-deflection curve,N [lbf],L=support span,mm[in.],b=width of beam tested,mm[in.],andd=depth of beam tested,mm[in.].N OTE10—Eq3applies strictly to materials for which stress is linearly proportional to strain up to the point of rupture and for which the strains are small.Since this is not always the case,a slight error will be introduced if Eq3is used to calculate stress for materials that are not true Hookean materials.The equation is valid for obtaining comparison data and for specification purposes,but only up to a maximumfiber strainof5%in the outer surface of the test specimen for specimens tested by the procedures described herein.N OTE11—When testing highly orthotropic laminates,the maximum stress may not always occur in the outer surface of the test specimen.4 Laminated beam theory must be applied to determine the maximum tensile stress at failure.If Eq3is used to calculate stress,it will yield an apparent strength based on homogeneous beam theory.This apparent strength is highly dependent on the ply-stacking sequence of highly orthotropic laminates.N OTE12—The preceding calculation is not valid if the specimen slips excessively between the supports.12.3Flexural Stress for Beams Tested at Large Support Spans(s f)—If support span-to-depth ratios greater than16to 1are used such that deflections in excess of10%of the support span occur,the stress in the outer surface of the specimen for a simple beam can be reasonably approximated with the following equation(see Note13):s f5~3PL/2bd2!@116~D/L!224~d/L!~D/L!#(4) where:s f,P,L,b,and d are the same as for Eq3,andD=deflection of the centerline of the specimen at the middle of the support span,mm[in.].N OTE13—When large support span-to-depth ratios are used,significant end forces are developed at the support noses which will affect the moment in a simple supported beam.Eq4includes additional terms that are an approximate correction factor for the influence of these end forces in large support span-to-depth ratio beams where relatively large deflec-tions exist.12.4Flexural Strength(s fM)—Maximumflexural stress sustained by the test specimen(see Note11)during a bendingtest.It is calculated according to Eq3or Eq4.Some materials that do not break at strains of up to5%may give a load deflection curve that shows a point at which the load does not increase with an increase in strain,that is,a yield point(Fig.1, Curve B),Y.Theflexural strength may be calculated for these materials by letting P(in Eq3or Eq4)equal this point,Y.12.5Flexural Offset Yield Strength—Offset yield strength is the stress at which the stress-strain curve deviates by a given strain(offset)from the tangent to the initial straight line portion of the stress-strain curve.The value of the offset must be given whenever this property is calculated.N OTE14—This value may differ fromflexural strength defined in12.4. Both methods of calculation are described in the annex to Test Method D638.12.6Flexural Stress at Break(s fB)—Flexural stress at break of the test specimen during a bending test.It is calculated according to Eq3or Eq4.Some materials may give a load deflection curve that shows a break point,B,without a yield point(Fig.1,Curve a)in which case s fB=s fM.Other materials may give a yield deflection curve with both a yield and a break point,B(Fig.1,Curve b).Theflexural stress at break may be calculated for these materials by letting P(in Eq 3or Eq4)equal this point,B.12.7Stress at a Given Strain—The stress in the outer surface of a test specimen at a given strain may be calculated in accordance with Eq3or Eq4by letting P equal the load read from the load-deflection curve at the deflection corresponding to the desired strain(for highly orthotropic laminates,see Note11).12.8Flexural Strain,e f—Nominal fractional change in the length of an element of the outer surface of the test specimen at midspan,where the maximum strain occurs.It may be calculated for any deflection using Eq5:e f56Dd/L2(5) where:e f=strain in the outer surface,mm/mm[in./in.],D=maximum deflection of the center of the beam,mm [in.],L=support span,mm[in.],andd=depth,mm[in.].12.9Modulus of Elasticity:12.9.1Tangent Modulus of Elasticity—The tangent modu-lus of elasticity,often called the“modulus of elasticity,”is the ratio,within the elastic limit,of stress to corresponding strain. It is calculated by drawing a tangent to the steepest initial straight-line portion of the load-deflection curve and using Eq 6(for highly anisotropic composites,see Note15).E B5L3m/4bd3(6)4For a discussion of these effects,see Zweben,C.,Smith,W.S.,and Wardle,M. W.,“Test Methods for Fiber Tensile Strength,Composite Flexural Modulus and Properties of Fabric-Reinforced Laminates,“Composite Materials:Testing and Design(Fifth Conference),ASTM STP674,1979,pp.228–262.N OTE—Curve a:Specimen that breaks before yielding.Curve b:Specimen that yields and then breaks before the5%strain limit.Curve c:Specimen that neither yields nor breaks before the5%strain limit.FIG.1Typical Curves of Flexural Stress(ßf)Versus FlexuralStrain(ef)where:E B =modulus of elasticity in bending,MPa [psi],L =support span,mm [in.],b =width of beam tested,mm [in.],d =depth of beam tested,mm [in.],andm =slope of the tangent to the initial straight-line portion of the load-deflection curve,N/mm [lbf/in.]of deflec-tion.N OTE 15—Shear deflections can seriously reduce the apparent modulusof highly anisotropic composites when they are tested at low span-to-depth ratios.4For this reason,a span-to-depth ratio of 60to 1is recommended for flexural modulus determinations on these composites.Flexural strength should be determined on a separate set of replicate specimens at a lower span-to-depth ratio that induces tensile failure in the outer fibers of the beam along its lower face.Since the flexural modulus of highly anisotropic laminates is a critical function of ply-stacking sequence,it will not necessarily correlate with tensile modulus,which is not stacking-sequence dependent.12.9.2Secant Modulus —The secant modulus is the ratio of stress to corresponding strain at any selected point on the stress-strain curve,that is,the slope of the straight line that joins the origin and a selected point on the actual stress-strain curve.It shall be expressed in megapascals [pounds per square inch].The selected point is chosen at a prespecified stress or strain in accordance with the appropriate material specification or by customer contract.It is calculated in accordance with Eq 6by letting m equal the slope of the secant to the load-deflection curve.The chosen stress or strain point used for the determination of the secant shall be reported.12.9.3Chord Modulus (E f )—The chord modulus may be calculated from two discrete points on the load deflection curve.The selected points are to be chosen at two prespecified stress or strain points in accordance with the appropriate material specification or by customer contract.The chosen stress or strain points used for the determination of the chord modulus shall be reported.Calculate the chord modulus,E f using the following equation:E f 5~s f 22s f 1!/~e f 22e f 1!(7)where:s f 2and s f 1are the flexural stresses,calculated from Eq 3or Eq 4and measured at the predefined points on the loaddeflection curve,and e f 2ande f 1are the flexural strain values,calculated from Eq 5and measured at the predetermined points on the load deflection curve.12.10Arithmetic Mean —For each series of tests,the arithmetic mean of all values obtained shall be calculated to three significant figures and reported as the “average value”for the particular property in question.12.11Standard Deviation —The standard deviation (esti-mated)shall be calculated as follows and be reported to two significant figures:s 5=~(X 22nX¯2!/~n 21!(8)where:s =estimated standard deviation,X =value of single observation,n =number of observations,andX ¯=arithmetic mean of the set of observations.13.Report13.1Report the following information:13.1.1Complete identification of the material tested,includ-ing type,source,manufacturer’s code number,form,principal dimensions,and previous history (for laminated materials,ply-stacking sequence shall be reported),13.1.2Direction of cutting and loading specimens,when appropriate,13.1.3Conditioning procedure,13.1.4Depth and width of specimen,13.1.5Procedure used (A or B),13.1.6Support span length,13.1.7Support span-to-depth ratio if different than 16:1,13.1.8Radius of supports and loading noses,if different than 5mm.When support and/or loading nose radii other than 5mm are used,the results shall be identified as being generated by a modified version of this test method and the referring specification referenced as to the geometry used.13.1.9Rate of crosshead motion,13.1.10Flexural strain at any given stress,average value and standard deviation,13.1.11If a specimen is rejected,reason(s)for rejection,13.1.12Tangent,secant,or chord modulus in bending,average value,standard deviation,and the strain level(s)used if secant or chord modulus,13.1.13Flexural strength (if desired),average value,and standard deviation,13.1.14Stress at any given strain up to and including 5%(if desired),with strain used,average value,and standard devia-tion,13.1.15Flexural stress at break (if desired),average value,and standard deviation,13.1.16Type of behavior,whether yielding or rupture,or both,or other observations,occurring within the 5%strain limit,and13.1.17Date of specific version of test used.TABLE 2Flexural ModulusMaterial Mean,103psiValues Expressed in units of %of 103psi V r A V R B r C R D ABS338 4.797.6913.621.8DAP thermoset 485 2.897.188.1520.4Cast acrylic 81013.716.138.845.4GR polyester816 3.49 4.209.9111.9GR polycarbonate 1790 5.52 5.5215.615.6SMC195010.913.830.839.1AV r =within-laboratory coefficient of variation for the indicated material.It is obtained by first pooling the within-laboratory standard deviations of the test results from all of the participating laboratories:Sr =[[(s 1)2+(s 2)2...+(s n )2]/n ]1/2then V r =(S r divided by the overall average for the material)3100.BV r =between-laboratory reproducibility,expressed as the coefficient of varia-tion:S R ={S r 2+S L 2}1/2where S L is the standard deviation of laboratory means.Then:V R =(S R divided by the overall average for the material)3100.Cr =within-laboratory critical interval between two test results =2.83V r .DR =between-laboratory critical interval between two test results =2.83V R.。

219316057_牛蒡根多糖动态高压微射流提取工艺优化及体外抗氧化活性研究

219316057_牛蒡根多糖动态高压微射流提取工艺优化及体外抗氧化活性研究

张辰辰,宋江峰,刘元法,等. 牛蒡根多糖动态高压微射流提取工艺优化及体外抗氧化活性研究[J]. 食品工业科技,2023,44(12):260−267. doi: 10.13386/j.issn1002-0306.2022070133ZHANG Chenchen, SONG Jiangfeng, LIU Yuanfa, et al. Optimization of Dynamic High Pressure Microfluidization-Assisted Extraction of Burdock Root Polysaccharide and Its in Vitro Antioxidant Activity[J]. Science and Technology of Food Industry, 2023,44(12): 260−267. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2022070133· 工艺技术 ·牛蒡根多糖动态高压微射流提取工艺优化及体外抗氧化活性研究张辰辰1,2,宋江峰1,2, *,刘元法3,耿宁宁1,马恺扬2,王 林1,李 莹2,*(1.江苏大学食品与生物工程学院,江苏镇江 212013;2.江苏省农业科学院农产品加工研究所,江苏南京 210014;3.白马未来食品研究院,江苏南京 211225)摘 要:本文采用动态高压微射流联合水提法对牛蒡根多糖提取工艺进行优化,并分析其红外光谱结构和单糖组成,评价其对DPPH·、·OH 和ABTS +·的清除活性。

结果表明:影响牛蒡根多糖得率的因素大小依次为微射流压力>浸提温度>液固比>提取时间>处理次数。

通过响应面优化试验确定牛蒡根多糖最佳提取工艺为:微射流压力148.0 MPa 、液固比25:1 mL/g 、处理次数2次、浸提温度63 ℃和提取时间1 h 。

Appendix XVI B. Microbiological Examination of Non-sterile Products in BP2012

Appendix XVI B. Microbiological Examination of Non-sterile Products in BP2012

British Pharmacopoeia Volume VAppendicesAppendix XVI B. Microbiological Examination of Non-sterile Products1. Tests for Specified Micro-organisms1(Ph. Eur. method 2.6.13)1 INTRODUCTIONThe tests described hereafter will allow determination of the absence or limited occurrence of specified micro-organisms that may be detected under the conditions described.The tests are designed primarily to determine whether a substance or preparation complies with an established specification for microbiological quality. When used for such purposes, follow the instructions given below, including the number of samples to be taken, and interpret the results as stated below.Alternative microbiological procedures, including automated methods, may be used, provided that their equivalence to the Pharmacopoeia method has been demonstrated.2 GENERAL PROCEDURESThe preparation of samples is carried out as described in general chapter 2.6.12.If the product to be examined has antimicrobial activity, this is insofar as possible removed or neutralised as described in general chapter 2.6.12.If surface-active substances are used for sample preparation, their absence of toxicity for micro-organisms and their compatibility with inactivators used must be demonstrated as described in general chapter 2.6.12.3 GROWTH-PROMOTING AND INHIBITORY PROPERTIES OF THE MEDIA, SUITABILITY OF THE TEST AND NEGATIVE CONTROLSThe ability of the test to detect micro-organisms in the presence of the product to be tested must be established. Suitability must be confirmed if a change in testing performance, or the product, which may affect the outcome of the test is introduced.3-1 Preparation of test strainsUse standardised stable suspensions of test strains or prepare them as stated below. Seed lot culture maintenance techniques (seed-lot systems) are used so that the viable micro-organisms used for inoculation are not more than 5 passages removed from the original master seed-lot.3-1-1 Aerobic micro-organisms Grow each of the bacterial test strains separately in casein soya bean digest broth or on casein soya bean digest agar at 30-35 °C for 18-24 h. Grow the test strain for Candida albicans separately on Sabouraud-dextrose agar or in Sabouraud-dextrose broth at 20-25 °C for 2-3 days.— Staphylococcus aureus such as ATCC 6538, NCIMB 9518, CIP 4.83 or NBRC 13276;— Pseudomonas aeruginosa such as ATCC 9027, NCIMB 8626, CIP 82.118 or NBRC 13275;— Escherichia coli such as ATCC 8739, NCIMB 8545, CIP 53.126 or NBRC 3972;— Salmonella enterica subsp. enterica serovar Typhimurium, such as ATCC 14028 or, as an alternative,Salmonella enterica subsp. enterica serovar Abony such as NBRC 100797, NCTC 6017 or CIP 80.39;— Candida albicans such as ATCC 10231, NCPF 3179, IP 48.72 or NBRC 1594.Use buffered sodium chloride-peptone solution pH 7.0 or phosphate buffer solution pH 7.2 to make test suspensions. Use the suspensions within 2 h or within 24 h if stored at 2-8 °C.3-1-2 Clostridia Use Clostridium sporogenes such as ATCC 11437 (NBRC 14293, NCIMB 12343, CIP 100651) or ATCC 19404 (NCTC 532 or CIP 79.03) or NBRC 14293. Grow the clostridial test strain under anaerobic conditions in reinforced medium for clostridia at 30-35 °C for 24-48 h. As an alternative to preparing and then diluting down a fresh suspension of vegetative cells of Cl. sporogenes, a stable spore suspension is used for test inoculation. The stable spore suspension may be maintained at 2-8 °C for a validated period.3-2 Negative controlTo verify testing conditions, a negative control is performed using the chosen diluent in place of the test preparation. There must be no growth of micro-organisms. A negative control is also performed when testing the products as described in section 4. A failed negative control requires an investigation.3-3 Growth promotion and inhibitory properties of the mediaTest each batch of ready-prepared medium and each batch of medium prepared either from dehydrated medium or from ingredients.Verify suitable properties of relevant media as described in Table 2.6.13.-1.Test for growth promoting properties, liquid mediaInoculate a portion of the appropriate medium with a small number (not more than 100 CFU) of the appropriate micro-organism. Incubate at the specified temperature for not more than the shortest period of time specified in the test. Clearly visible growth of the micro-organism comparable to that previously obtained with a previously tested and approved batch of medium occurs.Test for growth promoting properties, solid mediaPerform the surface-spread method, inoculating each plate with a small number (not more than 100 CFU) of the appropriate micro-organism. Incubate at the specified temperature for not more than the shortest period of time specified in the test. Growth of the micro-organism comparable to that previously obtained with a previously tested and approved batch of medium occurs.Test for inhibitory properties, liquid or solid mediaInoculate the appropriate medium with at least 100 CFU of the appropriate micro-organism. Incubate at the specified temperature for not less than the longest period of time specified in the test. No growth of the test micro-organism occurs.Test for indicative propertiesPerform the surface-spread method, inoculating each plate with a small number (not more than 100 CFU) of the appropriate micro-organism. Incubate at the specified temperature for a period of time within the range specified in the test. Colonies are comparable in appearance and indication reactions to those previously obtained with a previously tested and approved batch of medium.3-4 Suitability of the test methodFor each product to be tested, perform the sample preparation as described in the relevant paragraph in section 4. Add each test strain at the time of mixing, in the prescribed growth medium. Inoculate the test strains individually. Use a number of micro-organisms equivalent to not more than 100 CFU in the inoculated test preparation.Perform the test as described in the relevant paragraph in section 4 using the shortest incubation period prescribed.The specified micro-organisms must be detected with the indication reactions as described in section 4.Any antimicrobial activity of the product necessitates a modification of the test procedure (see 4-5-3 of general chapter 2.6.12).If for a given product the antimicrobial activity with respect to a micro-organism for which testing is prescribed cannot be neutralised, then it is to be assumed that the inhibited micro-organism will not be present in the product.4 TESTING OF PRODUCTS4-1 Bile-tolerant gram-negative bacteria4-1-1 Sample preparation and pre-incubation Prepare a sample using a 1 in 10 dilution of not less than 1 g of the product to be examined as described in general chapter 2.6.12, but using casein soya bean digest broth as the chosen diluent, mix and incubate at 20-25 °C for a time sufficient to resuscitate the bacteria but not sufficient to encourage multiplication of the organisms (usually 2 h but not more than 5 h).4-1-2 Test for absence Unless otherwise prescribed, use the volume corresponding to 1 g of the product, as prepared in 4-1-1, to inoculate enterobacteria enrichment broth-Mossel. Incubate at 30-35 °C for 24-48 h. Subculture on plates of violet red bile glucose agar. Incubate at 30-35 °C for 18-24 h.The product complies with the test if there is no growth of colonies.4-1-3 Quantitative test4-1-3-1 Selection and subculture Inoculate suitable quantities of enterobacteria enrichment broth-Mossel with the preparation as described under 4-1-1 and/or dilutions of it containing respectively 0.1 g, 0.01 g and 0.001 g (or 0.1 mL, 0.01 mL and 0.001 mL) of the product to be examined. Incubate at 30-35 °C for 24-48 h. Subculture each of the cultures on a plate of violet red bile glucose agar. Incubate at 30-35 °C for 18-24 h.4-1-3-2 Interpretation Growth of colonies constitutes a positive result. Note the smallest quantity of the product that gives a positive result and the largest quantity that gives a negative result. Determine from Table 2.6.13.-2 the probable number of bacteria.4-2 Escherichia coli4-2-1 Sample preparation and pre-incubation Prepare a sample using a 1 in 10 dilution of not less than 1 g of the product to be examined as described in general chapter 2.6.12, and use 10 mL or the quantity corresponding to 1 g or 1 mL to inoculate a suitable amount (determined as described under 3-4) of casein soya bean digest broth, mix and incubate at 30-35 °C for 18-24 h.4-2-2 Selection and subculture Shake the container, transfer 1 mL of casein soya bean digest broth to 100 mL of MacConkey broth and incubate at 42-44 °C for 24-48 h. Subculture on a plate of MacConkey agar at 30-35 °C for 18-72 h.4-2-3 Interpretation Growth of colonies indicates the possible presence of E. coli. This is confirmed by identification tests.The product complies with the test if no colonies are present or if the identification tests are negative.4-3 Salmonella4-3-1 Sample preparation and pre-incubation Prepare the product to be examined as described in general chapter 2.6.12, and use the quantity corresponding to not less than 10 g or 10 mL to inoculate a suitable amount (determined as described under 3-4) of casein soya bean digest broth, mix and incubate at 30-35 °C for 18-24 h.4-3-2 Selection and subculture Transfer 0.1 mL of casein soya bean digest broth to 10 mL of Rappaport Vassiliadis Salmonella enrichment broth and incubate at 30-35 °C for 18-24 h. Subculture on plates of xylose, lysine, deoxycholate agar. Incubate at 30-35 °C for 18-48 h.4-3-3 Interpretation The possible presence of Salmonella is indicated by the growth of well-developed, red colonies, with or without black centres. This is confirmed by identification tests.The product complies with the test if colonies of the types described are not present or if the confirmatory identification tests are negative.4-4 Pseudomonas aeruginosa4-4-1 Sample preparation and pre-incubation Prepare a sample using a 1 in 10 dilution of not less than 1 g of the product to be examined as described in general chapter 2.6.12, and use 10 mL or the quantity corresponding to 1 g or 1 mL to inoculate a suitable amount (determined as described under 3-4) of casein soya bean digest broth and mix. When testing transdermal patches, filter the volume of sample corresponding to 1 patch of the preparation described under 4-5-1 in general chapter 2.6.12 through a sterile filter membrane and place in 100 mL of casein soya bean digest broth. Incubate at 30-35 °C for 18-24 h.4-4-2 Selection and subculture Subculture on a plate of cetrimide agar and incubate at 30-35 °C for 18-72 h.4-4-3 Interpretation Growth of colonies indicates the possible presence of P. aeruginosa. This is confirmed by identification tests.The product complies with the test if colonies are not present or if the confirmatory identification tests are negative.4-5 Staphylococcus aureus4-5-1 Sample preparation and pre-incubation Prepare a sample using a 1 in 10 dilution of not less than 1 g of the product to be examined as described in general chapter 2.6.12, and use 10 mL or the quantity corresponding to 1 g or 1 mL to inoculate a suitable amount (determined as described under 3-4) of casein soya bean digest broth and mix. When testing transdermal patches, filter the volume of sample corresponding to 1 patch of the preparation described under 4-5-1 in general chapter 2.6.12 through a sterile filter membrane and place in 100 mL of casein soya bean digest broth. Incubate at 30-35 °C for 18-24 h.4-5-2 Selection and subculture Subculture on a plate of mannitol salt agar and incubate at 30-35 °C for 18-72 h.4-5-3 Interpretation The possible presence of S. aureus is indicated by the growth of yellow/white colonies surrounded by a yellow zone. This is confirmed by identification tests.The product complies with the test if colonies of the types described are not present or if the confirmatory identification tests are negative.4-6 Clostridia4-6-1 Sample preparation and heat treatment Prepare a sample using a 1 in 10 dilution (with a minimum total volume of 20 mL) of not less than 2 g or 2 mL of the product to be examined as described in general chapter 2.6.12.Divide the sample into 2 portions of at least 10 mL. Heat 1 portion at 80 °C for 10 min and cool rapidly. Do not heat the other portion.4-6-2 Selection and subculture Use 10 mL or the quantity corresponding to 1 g or 1 mL of the product to be examined of both portions to inoculate suitable amounts (determined as described under 3-4) of reinforced medium for clostridia. Incubate under anaerobic conditions at 30-35 °C for 48 h. After incubation, make subcultures from each container on Columbia agar and incubate under anaerobic conditions at 30-35 °C for 48-72 h.4-6-3 Interpretation The occurrence of anaerobic growth of rods (with or without endospores) giving a negative catalase reaction indicates the presence of clostridia. This is confirmed by identification tests.The product complies with the test if colonies of the types described are not present or if the confirmatory identification tests are negative.4-7 Candida albicans4-7-1 Sample preparation and pre-incubation Prepare the product to be examined as described in general chapter 2.6.12, and use 10 mL or the quantity corresponding to not less than 1 g or 1 mL to inoculate 100 mL of Sabouraud-dextrose broth and mix. Incubate at 30-35 °C for 3-5 days.4-7-2 Selection and subculture Subculture on a plate of Sabouraud-dextrose agar and incubate at 30-35 °C for 24 -48 h.4-7-3 Interpretation Growth of white colonies may indicate the presence of C. albicans. This is confirmed by identification tests.The product complies with the test if such colonies are not present or if the confirmatory identification tests are negative.The following section is given for information.5 RECOMMENDED SOLUTIONS AND CULTURE MEDIAThe following solutions and culture media have been found to be satisfactory for the purposes for which they are prescribed in the test for microbial contamination in the Pharmacopoeia. Other media may be used provided that their suitability can be demonstrated.Stock buffer solution Place 34 g of potassium dihydrogen phosphate in a 1000 mL volumetric flask, dissolve in 500 mL of purified water, adjust to pH 7.2 ± 0.2 with sodium hydroxide, dilute to 1000.0 mL with purified water and mix. Dispense into containers and sterilise. Store at 2-8 °C.Phosphate buffer solution pH 7.2 Prepare a mixture of stock buffer solution and purified water (1:800 V/V) and sterilise.Buffered sodium chloride-peptone solution pH 7.0Potassium dihydrogen phosphate 3.6 gDisodium hydrogen phosphate dihydrate7.2 g, equivalent to 0.067 M phosphateSodium chloride 4.3 gPeptone (meat or casein) 1.0 gPurified water1000 mLSterilise in an autoclave using a validated cycle.Casein soya bean digest brothPancreatic digest of casein17.0 gPapaic digest of soya bean 3.0 gSodium chloride 5.0 gDipotassium hydrogen phosphate 2.5 gGlucose monohydrate 2.5 gPurified water1000 mLAdjust the pH so that after sterilisation it is 7.3 ± 0.2 at 25 °C. Sterilise in an autoclave using a validated cycle. Casein soya bean digest agarPancreatic digest of casein15.0 gPapaic digest of soya bean 5.0 gSodium chloride 5.0 gAgar15.0 gPurified water1000 mLAdjust the pH so that after sterilisation it is 7.3 ± 0.2 at 25 °C. Sterilise in an autoclave using a validated cycle. Sabouraud-dextrose agarDextrose40.0 g Mixture of peptic digest of animal tissue and pancreatic digest of casein (1:1)10.0 g Agar15.0 g Purified water1000 mL Adjust the pH so that after sterilisation it is 5.6 ± 0.2 at 25 °C. Sterilise in an autoclave using a validated cycle. Potato dextrose agarInfusion from potatoes200 gDextrose20.0 gAgar15.0 gPurified water1000 mLAdjust the pH so that after sterilisation it is 5.6 ± 0.2 at 25 °C. Sterilise in an autoclave using a validated cycle. Sabouraud-dextrose brothDextrose20.0 g Mixture of peptic digest of animal tissue and pancreatic digest of casein (1:1)10.0 g Purified water1000 mLAdjust the pH so that after sterilisation it is 5.6 ± 0.2 at 25 °C. Sterilise in an autoclave using a validated cycle. Enterobacteria enrichment broth-MosselPancreatic digest of gelatin10.0 gGlucose monohydrate 5.0 g Dehydrated ox bile20.0 g Potassium dihydrogen phosphate 2.0 gDisodium hydrogen phosphate dihydrate8.0 gBrilliant green15 mgPurified water1000 mLAdjust the pH so that after heating it is 7.2 ± 0.2 at 25 °C. Heat at 100 °C for 30 min and cool immediately. Violet red bile glucose agarYeast extract 3.0 gPancreatic digest of gelatin7.0 gBile salts 1.5 gSodium chloride 5.0 gGlucose monohydrate10.0 gAgar15.0 gNeutral red30 mgCrystal violet 2 mgPurified water1000 mLAdjust the pH so that after heating it is 7.4 ± 0.2 at 25 °C. Heat to boiling; do not heat in an autoclave. MacConkey brothPancreatic digest of gelatin20.0 gLactose monohydrate10.0 gDehydrated ox bile 5.0 gBromocresol purple10 mgPurified water1000 mLAdjust the pH so that after sterilisation it is 7.3 ± 0.2 at 25 °C. Sterilise in an autoclave using a validated cycle. MacConkey agarPancreatic digest of gelatin17.0 gPeptones (meat and casein) 3.0 gLactose monohydrate10.0 gSodium chloride 5.0 gBile salts 1.5 gAgar13.5 gNeutral red30.0 mgCrystal violet 1 mgPurified water1000 mLAdjust the pH so that after sterilisation it is 7.1 ± 0.2 at 25 °C. Boil for 1 min with constant shaking then sterilise in an autoclave using a validated cycle.Rappaport Vassiliadis Salmonella enrichment brothSoya peptone 4.5 gMagnesium chloride hexahydrate29.0 gSodium chloride8.0 gDipotassium phosphate0.4 gPotassium dihydrogen phosphate0.6 gMalachite green0.036 gPurified water1000 mLDissolve, warming gently. Sterilise in an autoclave using a validated cycle, at a temperature not exceeding 115 °C. The pH is to be 5.2 ± 0.2 at 25 °C after heating and autoclaving.Xylose, lysine, deoxycholate agarXylose 3.5 gL-Lysine 5.0 gLactose monohydrate7.5 gSucrose7.5 gSodium chloride 5.0 gYeast extract 3.0 gPhenol red80 mgAgar13.5 gSodium deoxycholate 2.5 gSodium thiosulfate 6.8 gFerric ammonium citrate0.8 gPurified water1000 mLAdjust the pH so that after heating it is 7.4 ± 0.2 at 25 °C. Heat to boiling, cool to 50 °C and pour into Petri dishes. Do not heat in an autoclave.Cetrimide agarPancreatic digest of gelatin20.0 gMagnesium chloride 1.4 gDipotassium sulfate10.0 gCetrimide0.3 gAgar13.6 gPurified water1000 mLGlycerol10.0 mLHeat to boiling for 1 min with shaking. Adjust the pH so that after sterilisation it is 7.2 ± 0.2 at 25 °C. Sterilise in an autoclave using a validated cycle.Mannitol salt agarPancreatic digest of casein 5.0 gPeptic digest of animal tissue 5.0 gBeef extract 1.0 gD-Mannitol10.0 gSodium chloride75.0 gAgar15.0 gPhenol red0.025 gPurified water1000 mLHeat to boiling for 1 min with shaking. Adjust the pH so that after sterilisation it is 7.4 ± 0.2 at 25 °C. Sterilise in an autoclave using a validated cycle.Reinforced medium for clostridiaBeef extract10.0 gPeptone10.0 gYeast extract 3.0 gSoluble starch 1.0 gGlucose monohydrate 5.0 gCysteine hydrochloride0.5 gSodium chloride 5.0 gSodium acetate 3.0 gAgar0.5 gPurified water1000 mLHydrate the agar, dissolve by heating to boiling with continuous stirring. If necessary, adjust the pH so that after sterilisation it is 6.8 ± 0.2 at 25 °C. Sterilise in an autoclave using a validated cycle.Columbia agarPancreatic digest of casein10.0 gMeat peptic digest 5.0 gHeart pancreatic digest 3.0 gYeast extract 5.0 gMaize starch 1.0 gSodium chloride 5.0 gAgar, according to gelling power10.0-15.0 gPurified water1000 mLHydrate the agar, dissolve by heating to boiling with continuous stirring. If necessary, adjust the pH so that after sterilisation it is 7.3 ± 0.2 at 25 °C. Sterilise in an autoclave using a validated cycle. Allow to cool to 45-50 °C; add, where necessary, gentamicin sulfate corresponding to 20 mg of gentamicin base and pour into Petri dishes.2. Microbial Enumeration Tests1(Ph. Eur. method 2.6.12)1 INTRODUCTIONThe tests described hereafter will allow quantitative enumeration of mesophilic bacteria and fungi that may grow under aerobic conditions.The tests are designed primarily to determine whether a substance or preparation complies with an established specification for microbiological quality. When used for such purposes follow the instructions given below, including the number of samples to be taken, and interpret the results as stated below.The methods are not applicable to products containing viable micro-organisms as active ingredients.Alternative microbiological procedures, including automated methods, may be used, provided that their equivalence to the Pharmacopoeia method has been demonstrated.2 GENERAL PROCEDURESCarry out the determination under conditions designed to avoid extrinsic microbial contamination of the product to be examined. The precautions taken to avoid contamination must be such that they do not affect any micro-organisms that are to be revealed in the test.If the product to be examined has antimicrobial activity, this is insofar as possible removed or neutralised. If inactivators are used for this purpose, their efficacy and their absence of toxicity for micro-organisms must be demonstrated.If surface-active substances are used for sample preparation, their absence of toxicity for micro-organisms and their compatibility with inactivators used must be demonstrated.3 ENUMERATION METHODSUse the membrane filtration method or the plate-count methods, as prescribed. The most-probable-number (MPN) method is generally the least accurate method for microbial counts, however, for certain product groups with a very low bioburden, it may be the most appropriate method.The choice of method is based on factors such as the nature of the product and the required limit of micro-organisms. The chosen method must allow testing of a sufficient sample size to judge compliance with the specification. The suitability of the method chosen must be established.4 GROWTH PROMOTION TEST, SUITABILITY OF THE COUNTING METHOD AND NEGATIVE CONTROLS4-1 General considerationsThe ability of the test to detect micro-organisms in the presence of product to be tested must be established.Suitability must be confirmed if a change in testing performance, or the product, which may affect the outcome of the test is introduced.4-2 Preparation of test strainsUse standardised stable suspensions of test strains or prepare them as stated below. Seed lot culture maintenance techniques (seed-lot systems) are used so that the viable micro-organisms used for inoculation are not more than 5 passages removed from the original master seed-lot. Grow each of the bacterial and fungal test strains separately as described in Table 2.6.12.-1.Use buffered sodium chloride-peptone solution pH 7.0 or phosphate buffer solution pH 7.2 to make test suspensions; to suspend A. brasiliensis spores, 0.05 per cent of polysorbate 80 may be added to the buffer. Use the suspensions within 2 h or within 24 h if stored at 2-8 °C. As an alternative to preparing and then diluting a fresh suspension of vegetative cells of A. brasiliensis or B. subtilis, a stable spore suspension is prepared and then an appropriate volume of the spore suspension is used for test inoculation. The stable spore suspension may be maintained at 2-8 °C for a validated period of time.4-3 Negative controlTo verify testing conditions, a negative control is performed using the chosen diluent in place of the test preparation. There must be no growth of micro-organisms. A negative control is also performed when testing the products as described in section 5. A failed negative control requires an investigation.4-4 Growth promotion of the mediaTest each batch of ready-prepared medium and each batch of medium, prepared either from dehydrated medium or from the ingredients described.Inoculate portions/plates of casein soya bean digest broth and casein soya bean digest agar with a small number (not more than 100 CFU) of the micro-organisms indicated in Table 2.6.12.-1, using a separate portion/plate of medium for each. Inoculate plates of Sabouraud-dextrose agar with a small number (not more than 100 CFU) of the micro-organisms indicated in Table 2.6.12.-1, using a separate plate of medium for each. Incubate in the conditions described in Table 2.6.12.-1.For solid media, growth obtained must not differ by a factor greater than 2 from the calculated value for a standardised inoculum. For a freshly prepared inoculum, growth of the micro-organisms comparable to that previously obtained with a previously tested and approved batch of medium occurs. Liquid media are suitable if clearly visible growth of the micro-organisms comparable to that previously obtained with a previously tested and approved batch of medium occurs.4-5 Suitability of the counting method in the presence of product4-5-1 Preparation of the sample The method for sample preparation depends upon the physical characteristics of the product to be tested. If none of the procedures described below can be demonstrated to be satisfactory, an alternative procedure must be developed.Water-soluble products Dissolve or dilute (usually a 1 in 10 dilution is prepared) the product to be examined in buffered sodium chloride-peptone solution pH 7.0, phosphate buffer solution pH 7.2 or casein soya bean digest broth. If necessary, adjust to pH 6-8. Further dilutions, where necessary, are prepared with the same diluent.Non-fatty products insoluble in water Suspend the product to be examined (usually a 1 in 10 dilution is prepared) in buffered sodium chloride-peptone solution pH 7.0, phosphate buffer solution pH 7.2 or casein soya bean digest broth. A surface-active agent such as 1 g/L of polysorbate 80 may be added to assist the suspension of poorly wettable substances. If necessary, adjust to pH 6-8. Further dilutions, where necessary, are prepared with the same diluent.Fatty products Dissolve in isopropyl myristate, sterilised by filtration or mix the product to be examined with the minimum necessary quantity of sterile polysorbate 80 or another non-inhibitory sterile surface-active agent, heated if necessary to not more than 40 °C, or in exceptional cases to not more than 45 °C. Mix carefully and if necessary maintain the temperature in a water-bath. Add sufficient of the pre-warmed chosen diluent to make a 1 in 10 dilution of the original product. Mix carefully whilst maintaining the temperature for the shortest time necessary for the formation of an emulsion. Further serial tenfold dilutions may be prepared using the chosen diluent containing a suitable concentration of sterile polysorbate 80 or another non-inhibitory sterile surface-active agent.Fluids or solids in aerosol form Aseptically transfer the product into a membrane filter apparatus or a sterile container for further sampling. Use either the total contents or a defined number of metered doses from each of the containers tested.Transdermal patches Remove the protective cover sheets ('release liners') of the transdermal patches and place them, adhesive side upwards, on sterile glass or plastic trays. Cover the adhesive surface with a sterile porous。

微分超越函数

微分超越函数

a rX iv:mat h /412354v5[mat h.GM ]15Apr208DIFFERENTIALLY TRANSCENDENTAL FUNCTIONS ˇZarko Mijajlovi´c 1),Branko Maleˇs evi´c 2)1)Faculty of Mathematics,University of Belgrade,Studentski trg 16,11000Belgrade,Serbia 2)Faculty of Electrical Engineering,University of Belgrade,Bulevar Kralja Aleksandra 73,11000Belgrade,Serbia Abstract The aim of this article is to exhibit a method for proving that certain analytic functions are not solutions of algebraic differential equations.The method is based on model-theoretic properties of differential fields and prop-erties of certain known transcendental differential functions,as of Γ(x ).Fur-thermore,it also determines differential transcendence of solution of some functional equations.1Notation and preliminaries The theory DF 0of differential fields of characteristic 0is the theory of fields with additional two axioms that relate to the derivative D :D (x +y )=Dx +Dy,D (xy )=xDy +yDx.Thus,a model of DF 0is a differential field K =(K,+,·,D,0,1)where (K,+,·,0,1)is a field and D is a differential operator satisfying the above axioms.A.Robinson proved that DF 0has a model completion,and then defined DCF 0to be the modelcompletion of DF 0.Subsequently,L.Blum found simple axioms of DFC 0without refereing to differential polynomials in more than one variable,see [22].In the fol-lowing,if not otherwise stated,F ,K ,L ,...will denote differential fields,F,L,K,...their domains while F ∗,K ∗,L ∗,...will denote their field parts,i.e.F ∗=(F,+,·,0,1).Thus,F ∗[x 1,x 2,...,x n ]denotes the set of (ordinary)algebraic polynomials over F ∗in variables x 1,x 2,...,x n .The symbol L {X }denotes the ring of differential poly-nomials over L in the variable X .Hence,if f ∈L {X }then for some n ∈N ,N ={0,1,2,...},f =f (X,DX,...,D n X )where f ∈F ∗(x,y 1,y 2,...,y n ).Suppose L ⊆K .The symbol td(K |L )denotes the transcendental degree of K ∗over L ∗.The basic properties of td are described in the following proposition.Proposition1.1Let A⊆B⊂C be ordinary algebraicfields.Thena.td(B|A)≤td(C|A).b.td(C|A)=td(C|B)+td(B|A).The statement follows from the fact that every transcendental base of B over A can be extended to a transcendental base of C over A,see[15].If b∈K,then L(b)denotes the simple differential extension of L in K,i.e.L(b) is the smallest differential subfield of K containing both L and b.If L⊆K then b∈K is differential algebraic over L if and only if there is a non-zero differential polynomial f∈L{X}such that f(b,Db,D2b,...,D n b)=0;if b is not differential algebraic over L then b is differential transcendental over L.K is a differential algebraic extension of L if every b∈K is differential algebraic over L.Next,f=0 is algebraic differential equation if f∈L{X}.If f∈L{X}\L,the order of f, denoted by ord f,is the largest n such that D n X occurs in f.If f∈L we put ord f=−1and then we write f(a)=f for each a.For f∈L{X}we shall write occasionally f′instead of Df,and f(a)instead of f(a,Da,D2a,...,D n a)for each a and n=ord f.Models of DCF0are differentially closedfields.A differentialfield K is differen-tially closed if whenever f,g∈K{X},g is non-zero and ord f>ord g,there is an a∈K such that f(a)=0and g(a)=0.Let us observe that any differentially closed field is algebraically closed.The theory DCF0admits elimination of quantifiers and it is submodel complete(A.Robinson):if F⊆L,K then K F≡L F,i.e.K and L are elementary equivalent over F.Other notations,notions and results concerning differentialfields that will be used in this article will be as in[22]or[18].2Differential algebraic extensionsIn this section we shall state certain properties of extensions of differentialfields, which we need to prove the main theorem2.8.These properties,described by propositions2.1–2.5,parallel in most cases properties of algebraicfields(without differential operators),by replacing the notion of the algebraic degree with the notion of the transcendental degree offields and deg f by ord f.Proofs of these propositions are standard and can be found in the basic literature on differential fields and therefore they are omitted.Proposition2.1Suppose L⊆K and let b∈K.Then b is differentially algebraic over F if and only if td(L(b)|L)<∞.Suppose L⊆K and let a1,a2,...,a n∈K be differentially algebraic over L.ThenL(a1,a2,...,a i)=L(a1,a2,...,a i−1)(a i)and a i is differentially algebraic over L(a1,a2,...,a i−1)for each i=1,2,...,n.Thus, by propositions1.1and2.1we havetd(L(a1,a2,...,a n)|L)=td(L(a1,a2,...,a n)|L(a1,a2,...,a n−1))+...+td(L(a1)|L)<∞,so every b∈L(a1,...,a n)is differentially algebraic over L.Hence L(a1,...,a n)is differentially algebraic over L.Proposition2.2Let L⊆K and suppose b,a1,...,a n∈K.If a1,...,a n are differ-entially algebraic over L and b is differentially algebraic over L(a1,...,a n),then b is differentially algebraic over L.Proposition2.3If F⊆L⊆K and L is differentially algebraic over F and K is differentially algebraic over L then K is differentially algebraic over L.Proposition2.4Suppose L⊆K and b∈K.Then b is a differentially algebraic over L if and only if Db is differentially algebraic over L.Proposition2.5Suppose F⊆K and letL={b∈K:b is differentially algebraic over F}.Thena.L is a differential subfield of K extending differentially algebraic F.b.If K is differentially algebraic closed then L is differentially algebraic closed.Remark2.6There are differentialfields with elements not having functional rep-resentation.One example of this kind is the Hardyfield of germs of functions[5].Let us denote by M D the class of complex functions meromorphic on a complex domain D.If D=C then we shall write M instead of M D.Let C=C(z)be the differentialfield of complex rational functions.Then M is differentialfield and C⊆M.Further,let L={f∈M:f differentially algebraic over C}.By Proposition2.5L is a differential subfield of M extending differentially algebraic C.Assume that e,g are complex functions.If e is an entire function(i.e.holomor-phic in entirefinite complex plane)and g is meromorphic,then their composition e◦g is not necessary meromorphic,as the example e(z)=e z,g(z)=1/z shows. However,g◦e is meromorphic since g is a quotient of entire functions,and obviously entire functions are closed under compositions.The next proposition states that a similar property holds for algebraic differential functions.Proposition2.7Let e,g be complex algebraic differential functions over C.If e is entire and g is meromorphic,then g◦e is meromorphic and differentially algebraic over C.Proof.Suppose that g is a solution of an algebraic differential equation over C,i.e.f(z,g,Dg,...,D n g)≡0for some f∈C[z,u0,u1,...,u n].If e′=0then e is a constant,so we may assume the nontrivial case,that e′=0. There are rational expressionsλkj in e′,e′′,...such that(D k u)◦e=kj=1λkj D j(u◦e),u is any meromorphic function.In fact,the sequenceλkj satisfies the recurrent identityλk+1,j=(λ′kj+λk,j−1)/e′,λ11=1/e′,λk0=0,λkj=0if j>k.It is easy to see thatλkk=(1/e′)k.Letf1=f(e,y,λ11Dy,λ21Dy+λ22D2y,...,λn1Dy+...+λnn D n y). Then g◦e is a solution of f1=0:since(D k g)◦e= k j=1λkj D j(g◦e),it follows, taking h=g◦e,f1(z,h,Dh,...,D n h)=f(e,g◦e,(Dg)◦e,...,(D n g)◦e)=f(z,g,Dg,...,D n g)|z=e≡0.Therefore,g◦e is meromorphic and differentially algebraic over C.∇Let us mention that N.Steinmetz[24,Satz2.]has considered a proposition which is the converse of the one we proved above.The next theorem is a direct corollary of the propositions2.5and2.7,since L is afield and therefore it is closed under values of rational expressions.Theorem2.8Let a(z)be a complex differential transcendental function over C, f(z,u0,u1,...,u m,y1,...,y n)a rational expression over L,and assume that e1,...,e mare entire functions which are differentially algebraic over C,e′i =0,1≤i≤m.If bis meromorphic and f(z,b,b◦e1,...,b◦e m,Db,...,D n b)≡a(z)then b is differential transcendental over C.We shall use it in proofs of differential transcendentality of certain complex functions.In most cases functions e i(z)will be linear functionsαz+β,α=0, and f will be a polynomial over C(observe that C⊂L).Also,it is possible to consider differential transcendental functions when f is a rational expression over L,for example as a solution of the equation y′′(z)+y′(z)/y(z)+y(sin z)=Γ(z+1).3Differentially transcendental functionsSuppose L⊆K.Let R(x)be the differentialfield of real rational functions.The fol-lowing H¨o lder’s famous theorem asserts the differential transcendentality of Gamma function,see[9].Theorem3.1a.Γ(x)is not differentially algebraic over R(x).b.Γ(z)is not differentially algebraic over C(z).∇Now we shall use the differential transcendence ofΓ(z)and properties of differ-entialfields developed in the previous section to prove differential transcendentality over C of some analytic functions.Γ(z)is meromorphic and by H¨o lder’s theorem and Proposition2.4,Γ(z)∈L.Example3.2This example is an archetype of proofs,based on properties of dif-ferentialfields exhibited in the previous section,of differential transcendentality of some well known complex functions.The Riemann zeta function is differentially transcendental over C(Hilbert).First we observe thatζ(s)is meromorphic and that ζ(s)satisfies the well-known functional equation:ζ(s)=χ(s)ζ(1−s),whereχ(s)=(2π)s2) .Now,suppose thatζ(s)is differentially algebraic over C,i.e.thatζ(s)∈L.Then ζ(1−s)andζ(s)/ζ(1−s)belong to L,too,soχ(s)belongs to L.The elementary functions(2π)s,and cos(πsn s(k∈Z),whereχk(n)is Dirichlet character see[12],is differentially transcendental function over C.This follows from a well-known functional equationsL−k(s)=2sπs−1k−s+12)L−k(1−s)andL+k(s)=2sπs−1k−s+12)L+k(1−s),where k∈N. D.Gokhman also proved in[5],but in entirely different way,that Dirichlet series are differentially transcendental.Besides Riemann zeta function ζ(s)=L+1(s),Dirichlet eta functionη(s)=∞n=1(−1)n+11(2n+1)s=L−4(s)are transcendental differential functions as examples of Dirichlet series see[2,page 289].∇Example3.3Kurepa’s Function related to the Kurepa Left Factorial Hypothesis, see[7,problem B44],is defined by[14]:(1)K(z)=∞e−tt z−1e −πAlternating Kurepa’s function related to the alternating sums of factorials see [7,problem B43],is defined by[20]:(4)A(z)=∞e−tt z+1−(−1)z tsinπz+A1(z).Generally,each meromorphic solution of a functional equation(5)is transcendental differential function over thefield C.ovanovi´c introduced in[19]a sequence of meromorphic functionsK m(z)−K m(z−1)=K m−1(z),K−1(z)=Γ(z),K0(z)=K(z).By use of induction and Theorem2.8we can conclude that K m(z)are differential transcendental over C.Analogously,a sequence of meromorphic functions defined byA m(z)+A m(z−1)=A m−1(z),A−1(z)=Γ(z+1),A0(z)=A(z)is a sequences of transcendental differential functions over C.∇Example3.4The meromorphic functionH1(z)=∞ n=01Remark3.5We see that in Example3.4functionsΓ(z)and H1(z)are differentially algebraically dependent,i.e.g(Γ,H1)=0,where g(x,y)=x′′x−(x′)2−yx2.We do not know if similar dependencies exist for pairs(K,Γ)and(ζ,Γ).It is very likely that these pairs are in fact differentially transcendental.Example3.6W.Gautschi and J.Waldvogel considered in[4]a family of functions which satisfiesIα(x)=xIα−1(x)+Γ(α),α>−1,x>0.For each x0>0function f(α)=Iα(x0)can be continued meromorphically(with respect to the complexα,see[4]).By Theorem2.8the function f(α)is differential transcendental over C.∇Example3.7The Barnes G-function is defined by[1]:G(z+1)=(2π)z/2e−(z(z+1)+γz2)/2∞n=1 1+zΓ(1−z)d2 /Γ1−zΓ(1−z).By Theorem2.8each meromorphic solution of the functional equation(8)is differ-ential transcendental over C.∇Example3.9Letτ(n)be defined by∞n=1τ(n)q n=q∞ n=1(1−q n)24,q=e2πiz.Thisfunction wasfirst studied by[21].Ramanujan’s Dirichlet L-series defined byf(s)=∞ n=1τ(n)is differentially transcendental function over C.This follows from functional equation see[8,page173]:f(s)=(2π)sΓ(s)f(12−s)i.e.f(s)=−(2π)ssin(πs)11i=1(s−i) 1e x−1dx=Γ(p)ζ(p)is differentially transcendental over C.This follows from the functional equation ζ(1−s)=2(2π)−s cos(sπ[9]H¨o lder,O.,¨Uber die Eigenschaft der Gamma Funktion keiner algebraische Dif-ferentialgleichung zu gen¨u ng,Math.Ann.,28,(1887)1-13.[10]Ivi´c,A.,The Riemann zeta-function,(1985)John Wiley&Sons,New York.[11]Ivi´c,A.,Mijajlovi´c,ˇZ.,On Kurepa problems in number theory,Publ.Inst.Math.(N.S.)57(71),(1995)19–28.[12]Ireland,K.,Rosen,M.,A Classical Introduction to Modern Number Theory,(1982)Springer.[13]Kolchin,E.R.,Differential Algebra and Algebraic Groups,(1973)New York,Academic Press.[14]Kurepa,D-.,Left factorial in complex domain,Mathematica Balkanica3,(1973)297–307.[15]Lang,S.,Algebra,3rd ed.,(2002)Springer.[16]Maleˇs evi´c,B.,Some considerations in connection with Kurepa’s function,Univ.Beograd.Publ.Elektrotehn.Fak.,Ser.Mat.,14,(2003)26–36.[17]Maleˇs evi´c,B.,Some considerations in connection with alternating Kurepa’sfunction,Approved for Integral Transforms and Special Functions,(2008) /abs/math/0406236.[18]Marker,D.,Messmer,M.,Pillay,A.,Model Theory of Fields,(1996)Springer.[19]Milovanovi´c,G.,A sequence of Kurepa’s functions,Scientific Review,Ser.Sci.Eng.19-20,(1996)137–146.[20]Petojevi´c,A.,The function v M m(s;a,z)and some well-known sequences,Jour-nal of Integer Sequences,Vol.5(2002),Article02.16.[21]Ramanujan,S.,On certain arithmetical functions,Trans.Cambr.Phil.Soc.22,(1916)159–184.[22]Sacks,G.E.,Saturated Model Theory,(1972)W.A.Benjamin,Reading,Mas-sachusetts.[23]Slavi´c,D.,On the left factorial function of the complex argument,MathematicaBalkanica3,(1973)472–477.[24]Steinmetz,N.,¨Uber die faktorisierbaren L¨o sungen gew¨o hnlicher,MathematischeZeitschrift,170,(1980)169–180.。

On ws-convergence of product measures

On ws-convergence of product measures

rules in this model would have to be measurable as functions from (Ω, A) into (S, B (S )). Unless Ω is discrete, it is mathematically naive to expect that these barest of requirements would lead to an analytically satisfactory structure for the decision sciences mentioned above. For instance, if Ω is the usual Lebesgue unit interval [0, 1] and if S is the two-element set {0, 1}, then it is wellknown that the sequence (rn ) of Rademacher functions, as defined in Example 1.1, does not have a limit in any classical sense (and neither does any of its subsequences).1 It is true that by adding to S (i.e., by assuming thaerpretation as a decision and by taking S := {0, 1 2 , 1})
one can save the day for classical limits in this example: (rn ) converges weakly in L1 ([0, 1]) to the constant r∞ ≡ 1 2 . However, only for a very limited class of cost integrands g such weak convergence of (rn ) to r∞ entails convergence of the corresponding risks (Jg (rn )) to Jg (r∞ ). This deficiency can be detected quickly by considering the quadratic cost g (ω, s) := s2 . Then Jg (rn ) =

p-adic q-expansion of alternating sums of powers

p-adic q-expansion of alternating sums of powers

F (z, t) =
et
2 +
1
ezt

tn
= n=0 En(z) n! ,
cf.[1,
5].
We note that, by substituting z = 0, En(0) = En are the familiar n-th Euler numbers. Over five decades ago, Carlitz defined q-extension of Euler numbers and polynomials, cf.[1, 4, 5]. Recently, author gave another construction of q-Euler numbers and polynomials (see [1, 5, 9]). By using author’s q-Euler numbers and polynomials, we gave the alternating sums of powers of consecutive q-integers as follows: For m ≥ 1, we have
talks of q-extension, q is variously considered as an indeterminate, a complex number
q ∈ C, or a p-adic number q ∈ Cp. If q ∈ C, one normally assumes |q| < 1. If q ∈ Cp,
complex number field and the completion of algebraic closure of Qp, cf.[1, 4, 6, 10]. Let vp be the normalized exponential valuation of Cp with |p|p = p−vp(p) = p−1. When(−1)l[l]m q = (−1)n+1

AMSCO V-PRO MAX 低温 sterilization 系统(仅适用于非美国地区)说明书

AMSCO ® V-PRO ® MAX LOW TEMPERATURESTERILIZATION SYSTEM (For Use Outside U.S.A. Only)Item ________________________Location(s)_______________________________________________The Selections Checked Below Apply To This EquipmentUNIT POWER SUPPLY ❑North America:200-208/230 Vac, 3 phase, 50/60 Hz, 16 Amp ❑Europe/Asia:400 Vac, 3 phase, 50 Hz, 10 Amp ❑Japan:200 Vac, 3 phase, 50/60 Hz, 16 AmpLABELS AND MANUALS ❑French ❑Finnish ❑ Danish ❑Italian ❑Russian ❑ Portuguese ❑German ❑Polish ❑ Hungarian❑Spanish ❑ JapaneseMOUNTING❑Single Door, Cabinet ❑Single Door, Recessed ❑Double Door, CabinetAPPLICATIONThe Amsco V-PRO maX Low Temperature Sterilization System is intended for use in the terminal sterilization of properly prepared (cleaned, rinsed and dried) reusable metal and nonmetal medical devices used in Healthcare Facilities. The STERIS developed low pressure and low temperature Sterilization Cycles are suitable for sterilizing medical devices sensitive to heat and moisture.The Amsco V-PRO maX Low Temperature Sterilization System performs three pre-programmed Sterilization Cycles: the Lumen Cycle (approximately 55 minutes to complete), the Non Lumen Cycle (approximately 28minutes to complete) and the Flexible Cycle (approximately 35 minutes to complete).This sterilization system using the Lumen Cycle can sterilize* the following:1.Lumened and non-lumened instruments with diffusion-restricted spaces such as the hinged portion of forceps and scissors.2.Medical devices (including single, dual and triplechanneled rigid and semi-rigid endoscopes) with the following configurations:1•Single channeled devices with a stainless lumen thatis ≥0.77mm (~1/32") internal diameter (D) and ≤500mm (19-11/16") in length•Dual channeled devices with stainless lumens thatare ≥0.77mm (~1/32") ID and ≤ 527 mm (20-3/4") in length•Triple channeled devices with stainless lumens thatare either:»≥ 1.2 mm (~3/64") ID and ≤ 275 mm (~10-55/64")in length»≥ 1.8 mm (~5/64") ID and ≤ 310 mm (~12-13/64")in length»≥ 2.8 mm (~7/64") ID and ≤ 317 mm (12-31/64") in length1Validation testing for all channel/lumen sizes was conducted using a ma ximum of 20 lumens per loa d. Hospita l loa ds should not exceed this validated number of lumens. Validation studies were performed using a va lida tion loa d consisting of two instrument trays and two pouches for a total weight of 8.91kg (19.65 lb).This sterilization system using the Non Lumen Cycle can sterilize 2 non-lumened instruments including non-lumened rigid, semi-rigid and flexible endoscopes and non-lumened instruments with stainless-steel diffusion-restricted areas such as the hinged portion of forceps or scissors.2Validation studies conducted using validation load of two instrument trays and two pouches for a total weight of 8.91kg (19.65 lb).This sterilization system using the Flexible Cycle can sterilize single or dual lumen surgical flexible endoscopes (such as those used in ENT, Urology and Surgical Care) and bronchoscopes in either of two configurations:1.Two flexible endoscopes with a light cord (if not integral to endoscope) and mat with no additional load.3 The flexible endoscopes may contain either:» A single lumen with an inside diameter of ≥ 1 mm (~3/64") and a length of ≤ 1050 mm (41")»Or two lumens with:•One lumen with an inside diameter of ≥ 1 mm (~3/64") and a length of ≤ 998 mm (39")•And the other lumen with an inside diameter of ≥ 1mm (~3/64") and a length of ≤ 850 mm (33")3The valida tion studies were conducted with two flexible endoscopes, ea ch pa cka ged into a tra y with silicone ma t a nd light cord (if not integra l to endoscope).(Typical - details may vary.)2.One flexible endoscope with a light cord (if not integral toendoscope) and mat and additional non-lumenedinstruments including instruments with diffusion-restricted areas such as the hinged portion of forcepsand scissors.4The flexible endoscope may containeither:» A single lumen with an inside diameter of ≥ 1 mm (~3/64") and a length of ≤ 1050 mm (41")»Or two lumens with:•One lumen with an inside diameter of ≥ 1 mm(~3/64") and a length of ≤ 998 mm (39")•And the other lumen with an inside diameter of≥ 1mm (~3/64") and a length of ≤ 850 mm (33")4The validation studies were conducted with a flexible endoscope in a tray with silicone mat and light cord (if not integral to endoscope). Also included in the load were an additional instrument tray and one pouch for a total weight of 11kg (24lb).DESCRIPTIONThe Amsco V-PRO maX Low Temperature Sterilization System is specifically designed to only process goods using vaporized hydrogen peroxide under vacuum conditions. The process is fully automated, is compatible with a broad range of materials and has rapid Sterilization Cycle times. There are no toxic by-products created by the Sterilization Cycle – only water vapor and oxygen are produced.The Amsco V-PRO maX Low Temperature Sterilization System is NOT intended to process liquids, linens, powders or cellulose materials.The system utilizes specially designed, disposable, multi-use Cartridges (available separately) containing VAPROX® HC Sterilant and is available in either a single door (freestanding or recessed) or double door configuration.Articles to be sterilized are placed on a racking system within the aluminum chamber. An automated control enables the cycle to be started and monitored by the operator. The touch screen is user friendly and easy to operate.System installation requires no plumbing, ventilation or air supply – only a dedicated electrical connection is needed. A power cord is supplied for this connection.STANDARDSThis Amsco V-PRO maX Low Temperature Sterilization System meets the applicable requirements of the following standards, as certified by INTERTEK Testing Services:•Underwriters Laboratories (UL) Standard UL 61010-1, Second Edition•Canadian Standards Association (CSA) CAN/CSA 22.2 No. 61010-1, Second EditionGoverning Directive for the affixing of the CE mark: •Medical Device Directive (MDD) 2007/47/ECStandards applied to demonstrate conformity to the directives:•EN 61010-1•EN 60601-1-2•EN 14937•IEC 61010-2-040Each sterilization system is designed, fabricated, assembled and tested in accordance with all applicable sections of UL and CSA.SIZE (W X H X L)Overall Dimensions:•838 x 1908 x 973 mm (33 x 75-1/8 x 38-5/16")Chamber Size:•432 x 381 x 826 mm (17 x 15 x 32-1/2")Chamber Volume:•136 L (4.8 cubic feet)FEATURESThe chamber and door assembly are aluminum equipped with a silicone rubber gasket for each door and a welded backhead on single door units.Insulation fitted on the chamber wall exterior, door and backhead is 25mm (1") thick (nominal). Insulation is held in place with hook-and-loop closures.Insulation is constructed of asbestos- and chloride-free, oil and water resistant (silicone impregnated) fiberglass.Automatic door locking mechanism keeps the sterilization system door locked during the entire Sterilization Cycle. After cycle completion, air pressure is used to unlock the door. The sterilizer door cannot be opened if either electrical power or air pressure is lost during sterilizer operation. When sterilization system is in Standby mode, there are no door opening restrictions. Chamber heating is achieved through electric strip heaters attached to the chamber sides, bottom wall, door and backhead. Operating temperature is approximately 50°C (122°F)Sterilant cartridge interface only accepts VAPROX HC Sterilant Cartridges (Cups). The system control automatically tracks the amount of VAPROX HC Sterilant used and the Sterilant expiration date. The control prompts the user on the control display when a new Cup is needed.The proprietary Cartridge is equipped with a data matrix code to ensure the correct Cup is used in the sterilization unit and that the Cup contents are not expired; no Cup code (or other information) needs to be entered by the user.Catalytic converter receives outflow from chamber during all cycle phases. Catalytic converter converts hydrogen peroxideinto water vapor and oxygen.CartridgeInterfaceHMI Display PrinterOther Components:The following are furnished to obtain a complete working unit, ready for (but not including) connection to the facility service lines:•Resistive Thermal Detectors (RTDs) are installed for sensing and displaying temperature control of vaporizer and chamber. Signals from all system RTDs, converted into electrical impulses, provide accurate control inputs and readouts throughout the entire cycle.•Pressure Transducers are installed for sensing and displaying chamber pressure control. Signals from allsystem pressure transducers, converted into electricalimpulses, provide accurate control inputs and readouts throughout the entire cycle.•Pneumatic and Solenoid Valves and Switches are used in the sterilization system design to simplify piping andincrease serviceability.•Air Supply and Vacuum Filters are supplied to ensure air entering chamber is HEPA (High Efficiency Particulate Air) filtered (prevent chamber recontamination) and airexhausted from vacuum pump is free of entrapped oil and odor.•Sterilization System Panels are constructed of plastic and stainless steel.•Sterilization System Frame and support system is constructed of welded carbon steel with protective paint.•High Power Vacuum Pump is supplied to produce cycle vacuum pulses that remove air and moisture from thechamber. The direct drive rotary vane pump is quiet(<60dB) with low vibration. A powerful 2.2 kW (3 HP)motor produces a displacement of 90 m3/hr (53 CFM) and helps alleviate moisture sensitivity in the sterilization unit.The Sterilizer operating pressure is from atmosphericpressure down to less than 1 Torr.CONTROL DESCRIPTIONThe Amsco V-PRO maX Low Temperature Sterilization System is equipped with an Allen-Bradley Compact Logix™ (Panel View Plus™ 6 1000 Display1) control system and an impact printer.•Control Display Panel is located on the front of the sterilization unit in the center while facing the unit. Thiscolor touch panel provides user information and allows user inputs. The display is a 640 x 480 pixel resolution,10.4" screen. Use of this panel and associated screens isnormally self-explanatory. The screens are color coded for operator convenience as follows:»Control Screens -»Condition Phase - Green»Sterilize Phase - Blue»Aeration Phase - Violet»Service Screens - Light Blue»Option Screens - Purple»Alarm Screens - RedNOTE: This Sterilization System permits no manual control of the Sterilization Cycles.The Ready, Status, Standby and Cup Empty screensinclude a cup level indicator (similar to a cell phone battery indicator) in the lower right corner (see Typical Operator Screens). For normal operation, each bar representsapproximately four cycles remaining (e.g., four bars means cup contains enough sterilant for 13-16 cycles).•Printer is located on the front of the sterilization unit on the right side while facing the unit. This alphanumeric impact printer provides an easy to read permanent record of the Sterilization Cycle. Printer provides a 5.7cm (2-1/4"), 24-character wide cycle tape and paper take-up.1CompactLogix™ and PanelView™ Plus 6 1000 are trademarks ofAllen-Bradley, a Rockwell Automation Company.p yTypical Operator ScreensCYCLE DESCRIPTIONThe Amsco V-PRO maX Low Temperature Sterilization System is equipped with three pre-programmed Sterilization Cycles: Lumen Cycle (approximately 55 minutes to complete),Non Lumen Cycle (approximately 28 minutes to complete) and Flexible Cycle (approximately 35 minutes to complete). Each Sterilization Cycle proceeds through three phases: CONDITION, STERILIZE and AERATION.•CONDITION – Lumen Cycle: This cycle phase is a set time vacuum pulse to remove air and moisture from thechamber. When setpoint is reached, load is tested foracceptable moisture content. If content is acceptable,cycle proceeds. If not, Condition pulse repeats.Non Lumen Cycle: This cycle phase is a vacuum pulse to remove air and moisture from the chamber. When setpoint is reached, load is tested for acceptable moisture content. If content is acceptable, cycle proceeds. If not, Condition pulse as identified for Lumen Cycle is initiated.Flexible Cycle: This cycle phase is a vacuum pulse toremove air and moisture from the chamber. When setpoint is reached, load is tested for acceptable moisture content. If content is acceptable, cycle proceeds. If not, Condition pulse as identified for Lumen Cycle is initiated.NOTE: If Condition phase fails the second moisture check, the cycle Aborts.•STERILIZE – This cycle phase is a series of four pulses.Each pulse consists of: vacuum pulled to setpoint;VAPROX HC Sterilant vapor drawn into chamber; hold for programmed time; filtered air is introduced to setpoint; hold for programmed time; deep vacuum pulled to setpoint.•AERATION – This cycle phase pulls a vacuum to setpoint and continues to evacuate for programmed time to reduce chamber vapor concentration. Once Aeration phase iscomplete, chamber pressure returns to atmospheric and chamber door is unlocked.PREVENTIVE MAINTENANCECustomers are encouraged to contact STERIS concerning annual maintenance programs. Preventive maintenance, adjustments and replacement of worn parts are provided on a scheduled basis to help ensure optimal equipment performance and help minimize untimely and costly interruptions. STERIS maintains a worldwide staff of well-equipped, factory-trained technicians to provide these services, as well as on-site installation, training, and expert repair services. Contact STERIS for details.CUSTOMER IS RESPONSIBLE FOR COMPLIANCE WITH APPLICABLE LOCAL AND NATIONAL CODES AND REGULATIONS.NOTES1.For general installation information, refer to STERIS GeneralNotes for Sterilizers (drawing 062941-091). This drawing should always accompany the equipment drawing.2.Refer to equipment drawing showing all utility and spacerequirements for actual installation specifications.Clearances shown are minimum required for servicingequipment. Floor surface must be hard and level.3.STERIS recommends maintaining and operatingsterilization system in area where temperature does not exceed 40°C (104°F) and has ventilation systemexchanging area air at least 10 times per hour.4.STERIS recommends a dedicated, grounded electricalcircuit be provided for each unit. Use of an extension cord is not recommended.5.Consult MSDS regarding storage and handling ofVAPROX HC Sterilant Cartridges (Cups).6.Unit weight: Single Door – 386 kg (850 lb) recessed and463kg (1020 lb) free-standing; Double Door – 562kg(1240lb) recessed one wall.7.Heat loss at 21°C (70°F) – Peak=1,046 BTU/hr;Avg.=942BTU/hr.8.Electrical Consumption, per cycle=2.2 kW-hr average;out of cycle=0.7 kW-hr average.9.STERIS assumes no responsibility for changes to theSterilization Unit made necessary through failure to observe the supplied necessary specifications (e.g., incorrect facility power supply). Specifications are subject to change without notice.EQUIPMENT DRAWINGS (REQUIRED FOR INSTALLATION)Equipment DrawingPart NumberEquipment Drawing Title129385-449Single Door, Recessed 129385-450Single Door, Cabinet 129385-451Double Door, CabinetSINGLE DOOR, CABINET MODEL SHOWNDimensions are in inches [mm]Not Fo rI n s t a l l at i o n SIDE VIEW PLAN VIEWFRONT VIEWDrawing is not to scale.Dimensions are typical.30 1/2[775]DOOR SWINGFor Further Information, contact:STERIS Corporation5960 Heisley RoadMentor, OH 44060-1834 • USA440-354-2600 • 800-548-4873This document is intended for the exclusive use of STERIS Customers, includingarchitects or designers. Reproduction in whole or in part by any party other than。

科学文献

1 The referee has pointed out that Bochner did work in this directon; see Trans. Amer. Math. Soc. 47 (1940), 146{164.
vanishes for all 2 C .
@ D = ( @@z + (1 + )Az ; @z + (1 + ?1 )Az )
2. Holomorphic methods
UNITONS AND THEIR MODULI
9
of the minimal spheres and the discovery that the area spectrum was discrete. Calabi's work was followed by work of physicists and mathematicians on maps into complex projective spaces and Grassmannians, and then Uhlenbeck's work on maps into U(N ). Since Grassmannians are symmetric spaces in U(N ) (they are the components of fS 2 U(N ) : S 2 = Ig) and are totally geodesically embedded via the ? Cartan embedding (V C N 7! V ? V ; V = projection onto V ); Uhlenbeck's results subsume the previous work. Finally, symmetric spaces contain U(N ) as a symmetric space of U(N ) U(N ) and unitons can be treated in this most general context (see BuRa]), although we will not do so now. The present work rests on the observation of Ward and Uhlenbeck that the harmonic map equations for maps R2 ! U(N ) are dimensionally reduced Bogomolny equations on R2+1. Ward ( Wa]) additionally observed that Hitchin's ( Hi]) equivalence of Bogomolny solutions on R3 and holomorphic bundles on T P1 = T S2 = foriented lines in R3g applied to maps R2 ! SU(N ), and showed how this construction naturally `compacti ed' for maps S! SU(2). In An2] we show that this equivalence can be `compacti ed', identifying nite-energy harmonic maps S2 ! U(N ) with bundles which are the restriction of bundles on the brewise compacti cation of T P1, a Hirzebruch surface. f = The uniton bundles are bundles on T P1 def P(O O(2)), the brewise compacti cation of the tangent bundle T P1 of the complex projective line. 1 Let ( ; ) and ( ^ = 1= ; ^ = = 2) be coordinates on T P1 = OP(2), where is the usual coordinate on P1 and is the coordinate associated to d=d . Meromorphic f sections (s) of T P1 give all the holomorphic sections of T P1 ( s; 1] in projective 1 ), save one. We x notation for the lines on T P1 : f f coordinates on T P P = ?1 ( ) = a p bre (silent p); Ga;b;c = ( ; a ? 2b ? c 2 ; 2] ; for (a; b; c) 2 C 3 = H 0(P1; T P1); (3.1) f G1 = f( ; 1; 0])g = in nity section of T P1 : To encode unitarity, we need the real structure (3.2) ( ; ) = (1= ; ? ?2 ) f acting on T P1 and compatibly on C 3 = H 0(P1; O(2)), the space of nite sections: (3.3) (a; b; c) = (c; ?b; a): We similarly de ne time translation t : ( ; ) 7! ( ; ? 2t ); (3.4) (a; b; c) 7! (a; b + t; c): De nition (Uniton Bundles). A rank N , or U(N ), uniton bundle, V , is a holof morphic rank N bundle on T P1 which is a) trivial when restricted to the following 1: f curves in T P 1. the section at in nity (G1 ), 2. nonpolar bres (i.e. P for 2 C ), 3. real sections of T P1 (sections invariant under , G(z;it;z) );

英语词汇表(level_4)


alter alternative although altitude altogether aluminium always amaze ambition ambulance America American among amongst amount ampere amplify amuse analyse analysis ancestor anchor ancient and angel anger angle angry animal ankle announce announcer annoy annual another answer ant anticipate anxiety anxious any anybody anyhow anyone anything anyway anywhere apart apartment apologize apology apparatus apparent appeal appear appearance appetite apple appliance applicable application apply appoint appointment appreciate
序号 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64
addition additional address adequate adjective adjust administration admire admission admit adopt adult advance advanced advantage adventure adverb advertisement advice advisable advise aeroplane affair affect affection afford afraid Africa African after afternoon afterward again against age agency agent aggressive ago agony agree agreement agriculture ahead aid aim air aircraft airline airplane airport alarm alcohol alike alive all allow alloy almost alone along aloud alphabet already also

Clinical Safety Data Management临床安全数据管理(E2A)

European Medicines Agency7 Westferry Circus, Canary Wharf, London, E14 4HB, UKTel. (44-20) 74 18 85 75 Fax (44-20) 75 23 70 40E-mail: mail@emea.eu.int http://www.emea.eu.intJune 1995 CPMP/ICH/377/95ICH Topic E 2 AClinical Safety Data Management: Definitions and Standards for Expedited ReportingStep 5NOTE FOR GUIDANCE ON CLINICAL SAFETY DATA MANAGEMENT:DEFINITIONS AND STANDARDSFOR EXPEDITED REPORTING(CPMP/ICH/377/95)APPROVAL BY CPMP November 1994 DATE FOR COMING INTO OPERATION June 1995CLINICAL SAFETY DATA MANAGEMENT: DEFINITIONS AND STANDARDS FOREXPEDITED REPORTINGICH Harmonised Tripartite Guideline1. INTRODUCTIONIt is important to harmonise the way to gather and, if necessary, to take action on important clinical safety information arising during clinical development. Thus, agreed definitions and terminology, as well as procedures, will ensure uniform Good Clinical Practice standards in this area. The initiatives already undertaken for marketed medicines through the CIOMS-1 and CIOMS-2 Working Groups on expedited (alert) reports and periodic safety update reporting, respectively, are important precedents and models. However, there are special circumstances involving medicinal products under development, especially in the early stages and before any marketing experience is available. Conversely, it must be recognised that a medicinal product will be under various stages of development and/or marketing in different countries, and safety data from marketing experience will ordinarily be of interest to regulators in countries where the medicinal product is still under investigational-only (Phase 1, 2, or 3) status. For this reason, it is both practical and well-advised to regard pre-marketing and post-marketing clinical safety reporting concepts and practices as interdependent, while recognising that responsibility for clinical safety within regulatory bodies and companies may reside with different departments, depending on the status of the product (investigational vs. marketed).There are two issues within the broad subject of clinical safety data management that are appropriate for harmonisation at this time:1. the development of standard definitions and terminology for key aspects of clinicalsafety reporting, and2. the appropriate mechanism for handling expedited (rapid) reporting, in theinvestigational (i.e., pre-approval) phase.The provisions of this guideline should be used in conjunction with other ICH Good Clinical Practice guidelines.TERMINOLOGY ASSOCIATED WITH CLINICAL2. DEFINITIONSANDSAFETY EXPERIENCEA. BasicTermsDefinitions for the terms adverse event (or experience), adverse reaction, and unexpected adverse reaction have previously been agreed to by consensus of the more than 30 Collaborating Centres of the WHO International Drug Monitoring Centre (Uppsala, Sweden). [Edwards, I.R., et al, Harmonisation in Pharmacovigilance. Drug Safety 10(2): 93-102, 1994.] Although those definitions can pertain to situations involving clinical investigations, some minor modifications are necessary, especially to accommodate the pre-approval, development environment.The following definitions, with input from the WHO Collaborative Centre, have been agreed:1. Adverse Event (or Adverse Experience)Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.An adverse event (AE) can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.2. Adverse Drug Reaction (ADR)In the pre-approval clinical experience with a new medicinal product or its new usages, particularly as the therapeutic dose(s) may not be established:all noxious and unintended responses to a medicinal product related to any dose should be considered adverse drug reactions.The phrase "responses to a medicinal products" means that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility, i.e., the relationship cannot be ruled out.Regarding marketed medicinal products, a well-accepted definition of an adverse drug reaction in the post-marketing setting is found in WHO Technical Report 498 [1972] and reads as follows:A response to a drug which is noxious and unintended and which occurs at dosesnormally used in man for prophylaxis, diagnosis, or therapy of disease or for modification of physiological function.The old term "side effect" has been used in various ways in the past, usually to describe negative (unfavourable) effects, but also positive (favourable) effects. It is recommended that this term no longer be used and particularly should not be regarded as synonymous with adverse event or adverse reaction.3. Unexpected Adverse Drug ReactionAn adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g., Investigator's Brochure for an unapproved investigational medicinal product). (See section III.C.)B. Serious Adverse Event or Adverse Drug ReactionDuring clinical investigations, adverse events may occur which, if suspected to be medicinal product-related (adverse drug reactions), might be significant enough to lead to important changes in the way the medicinal product is developed (e.g., change in dose, population, needed monitoring, consent forms). This is particularly true for reactions which, in their most severe forms, threaten life or function. Such reactions should be reported promptly to regulators.Therefore, special medical or administrative criteria are needed to define reactions that, either due to their nature ("serious") or due to the significant, unexpected information they provide, justify expedited reporting.To ensure no confusion or misunderstanding of the difference between the terms "serious" and "severe," which are not synonymous, the following note of clarification is provided: The term "severe" is often used to describe the intensity (severity) of a specific event (as in mild, moderate, or severe myocardial infarction); the event itself, however, may be of relatively minor medical significance (such as severe headache). This is not the same as "serious," which is based on patient/event outcome or action criteria usually associated with events that pose a threat to a patient's life or functioning. Seriousness (not severity) serves as a guide for defining regulatory reporting obligations.After reviewing the various regulatory and other definitions in use or under discussion elsewhere, the following definition is believed to encompass the spirit and meaning of them all:A serious adverse event (experience) or reaction is any untoward medicaloccurrence that at any dose:indeath,• resultslife-threatening,• isNOTE:T he term "life-threatening" in the definition of "serious" refers to an event in which the patient was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe.• requires inpatient hospitalisation or prolongation of existing hospitalisation,• results in persistent or significant disability/incapacity, or• is a congenital anomaly/birth defect.Medical and scientific judgement should be exercised in deciding whether expedited reporting is appropriate in other situations, such as important medical events that may not be immediately life-threatening or result in death or hospitalisation but may jeopardise the patient or may require intervention to prevent one of the other outcomes listed in the definition above. These should also usually be considered serious.Examples of such events are intensive treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalisation; or development of drug dependency or drug abuse.C. Expectedness of an Adverse Drug ReactionThe purpose of expedited reporting is to make regulators, investigators, and other appropriate people aware of new, important information on serious reactions. Therefore, such reporting will generally involve events previously unobserved or undocumented, and a guideline is needed on how to define an event as "unexpected" or "expected" (expected/unexpected from the perspective of previously observed, not on the basis of what might be anticipated from the pharmacological properties of a medicinal product).As stated in the definition (II.A.3.), an "unexpected" adverse reaction is one, the nature or severity of which is not consistent with information in the relevant source document(s). Until source documents are amended, expedited reporting is required for additional occurrences of the reaction.The following documents or circumstances will be used to determine whether an adverse event/reaction is expected:1. For a medicinal product not yet approved for marketing in a country, a company'sInvestigator's Brochure will serve as the source document in that country. (See section III.F. and ICH Guideline for the Investigator's Brochure.)2. Reports which add significant information on specificity or severity of a known,already documented serious ADR constitute unexpected events. For example, an event more specific or more severe than described in the Investigator's Brochure would be considered "unexpected". Specific examples would be (a) acute renal failure as a labeled ADR with a subsequent new report of interstitial nephritis and (b) hepatitis with a first report of fulminant hepatitis.3. STANDARDS FOR EXPEDITED REPORTINGA. What Should be Reported?1. Single Cases of Serious, Unexpected ADRsAll adverse drug reactions (ADRs) that are both serious and unexpected are subject to expedited reporting. This applies to reports from spontaneous sources and from any type of clinical or epidemiological investigation, independent of design or purpose. It also applies to cases not reported directly to a sponsor or manufacturer (for example, those found in regulatory authority-generated ADR registries or in publications). The source of a report (investigation, spontaneous, other) should always be specified.Expedited reporting of reactions which are serious but expected will ordinarily be inappropriate. Expedited reporting is also inappropriate for serious events from clinical investigations that are considered not related to study product, whether the event is expected or not. Similarly, non-serious adverse reactions, whether expected or not, will ordinarily not be subject to expedited reporting.Information obtained by a sponsor or manufacturer on serious, unexpected reports from any source should be submitted on an expedited basis to appropriate regulatory authorities if the minimum criteria for expedited reporting can be met. See section III.B.Causality assessment is required for clinical investigation cases. All cases judged by either the reporting health care professional or the sponsor as having a reasonable suspected causal relationship to the medicinal product qualify as ADRs. For purposes of reporting, adverse event reports associated with marketed drugs (spontaneous reports) usually imply causality. Many terms and scales are in use to describe the degree of causality (attributability) between a medicinal product and an event, such as certainly, definitely, probably, possibly or likely related or not related. Phrases such as "plausible relationship," "suspected causality," or "causal relationship cannot be ruled out" are also invoked to describe cause and effect. However, there is currently no standard international nomenclature. The expression "reasonable causal relationship" is meant to convey in general that there are facts (evidence) or arguments to suggest a causal relationship.Observations2. OtherThere are situations in addition to single case reports of "serious" adverse events or reactions that may necessitate rapid communication to regulatory authorities; appropriate medical and scientific judgement should be applied for each situation. In general, information that mightmaterially influence the benefit-risk assessment of a medicinal product or that would be sufficient to consider changes in medicinal product administration or in the overall conduct of a clinical investigation represents such situations. Examples include:a) For an "expected," serious ADR, an increase in the rate of occurrence which is judgedto be clinically important.b) A significant hazard to the patient population, such as lack of efficacy with a medicinalproduct used in treating life-threatening disease.c) A major safety finding from a newly completed animal study (such ascarcinogenicity).B. Reporting Time Frames1. Fatal or Life-Threatening Unexpected ADRsCertain ADRs may be sufficiently alarming so as to require very rapid notification to regulators in countries where the medicinal product or indication, formulation, or population for the medicinal product are still not approved for marketing, because such reports may lead to consideration of suspension of, or other limitations to, a clinical investigations program. Fatal or life-threatening, unexpected ADRs occurring in clinical investigations qualify for very rapid reporting. Regulatory agencies should be notified (e.g., by telephone, facsimile transmission, or in writing) as soon as possible but no later than 7 calendar days after first knowledge by the sponsor that a case qualifies, followed by as complete a report as possible within 8 additional calendar days. This report must include an assessment of the importance and implication of the findings, including relevant previous experience with the same or similar medicinal products.2. All Other Serious, Unexpected ADRsSerious, unexpected reactions (ADRs) that are not fatal or life-threatening must be filed as soon as possible but no later than 15 calendar days after first knowledge by the sponsor that the case meets the minimum criteria for expedited reporting.3. Minimum criteria for reportingInformation for final description and evaluation of a case report may not be available within the required time frames for reporting outlined above. Nevertheless, for regulatory purposes, initial reports should be submitted within the prescribed time as long as the following minimum criteria are met: an identifiable patient; a suspect medicinal product; an identifiable reporting source; and an event or outcome that can be identified as serious and unexpected, and for which, in clinical investigation cases, there is a reasonable suspected causal relationship. Follow-up information should be actively sought and submitted as it becomes available.ReporttoC. HowThe CIOMS-I form has been a widely accepted standard for expedited adverse event reporting. However, no matter what the form or format used, it is important that certain basic information/data elements, when available, be included with any expedited report, whether in a tabular or narrative presentation. The listing in Attachment 1 addresses those data elements regarded as desirable; if all are not available at the time of expedited reporting, efforts should be made to obtain them. (See section III.B.)All reports must be sent to those regulators or other official parties requiring them (as appropriate for the local situation) in countries where the drug is under development.D. Managing Blinded Therapy CasesWhen the sponsor and investigator are blinded to individual patient treatment (as in a double-blind study), the occurrence of a serious event requires a decision on whether to open (break) the code for the specific patient. If the investigator breaks the blind, then it is assumed the sponsor will also know the assigned treatment for that patient. Although it is advantageous to retain the blind for all patients prior to final study analysis, when a serious adverse reaction is judged reportable on an expedited basis, it is recommended that the blind be broken only for that specific patient by the sponsor even if the investigator has not broken the blind. It is also recommended that, when possible and appropriate, the blind be maintained for those persons, such as biometrics personnel, responsible for analysis and interpretation of results at the study's conclusion.There are several disadvantages to maintaining the blind under the circumstances described which outweigh the advantages. By retaining the blind, placebo and comparator (usually a marketed product) cases are filed unnecessarily. When the blind is eventually opened, which may be many weeks or months after reporting to regulators, it must be ensured that company and regulatory data bases are revised. If the event is serious, new, and possibly related to the medicinal product, then if the Investigator's Brochure is updated, notifying relevant parties of the new information in a blinded fashion is inappropriate and possibly misleading. Moreover, breaking the blind for a single patient usually has little or no significant implications for the conduct of the clinical investigation or on the analysis of the final clinical investigation data. However, when a fatal or other "serious" outcome is the primary efficacy endpoint in a clinical investigation, the integrity of the clinical investigation may be compromised if the blind is broken. Under these and similar circumstances, it may be appropriate to reach agreement with regulatory authorities in advance concerning serious events that would be treated as disease-related and not subject to routine expedited reporting.IssuesE. Miscellaneous1. Reactions Associated with Active Comparator or Placebo TreatmentIt is the sponsor's responsibility to decide whether active comparator drug reactions should be reported to the other manufacturer and/or directly to appropriate regulatory agencies. Sponsors must report such events to either the manufacturer of the active control or to appropriate regulatory agencies. Events associated with placebo will usually not satisfy the criteria for an ADR and, therefore, for expedited reporting.2. Products with More than one Presentation or UseTo avoid ambiguities and uncertainties, an ADR that qualifies for expedited reporting with one presentation of a product (e.g., a dosage form, formulation, delivery system) or product use (e.g., for an indication or population), should be reported or referenced to regulatory filings across other product presentations and uses.It is not uncommon that more than one dosage form, formulation, or delivery system (oral, IM, IV, topical, etc.) of the pharmacologically active compound(s) is under study or marketed; for these different presentations there may be some marked differences in the clinical safety profile. The same may apply for a given product used in different indications or populations (single dose vs. chronic administration, for example). Thus, "expectedness" may be product or product-use specific, and separate Investigator's Brochures may be used accordingly. However, such documents are expected to cover ADR information that applies to all affected product presentations and uses. When relevant, separate discussions of pertinent product-specific or use-specific safety information will also be included.It is recommended that any adverse drug reactions that qualify for expedited reporting observed with one product dosage form or use be cross referenced to regulatory records for all other dosage forms and uses for that product. This may result in a certain amount of overreporting or unnecessary reporting in obvious situations (for example, a report of phlebitis on IV injection sent to authorities in a country where only an oral dosage form is studied or marketed). However, underreporting is completely avoided.Events3. Post-studyAlthough such information is not routinely sought or collected by the sponsor, serious adverse events that occurred after the patient had completed a clinical study (including any protocol-required post-treatment follow-up) will possibly be reported by an investigator to the sponsor. Such cases should be regarded for expedited reporting purposes as though they were study reports. Therefore, a causality assessment and determination of expectedness are needed for a decision on whether or not expedited reporting is required.F. Informing Investigators and Ethics Committees/Institutional Review Boards ofNew Safety InformationInternational standards regarding such communication are discussed within the ICH GCP Guidelines, including the addendum on "Guideline for the Investigator's Brochure." In general, the sponsor of a study should amend the Investigator's Brochure as needed, and in accord with any local regulatory requirements, so as to keep the description of safety information updated.ATTACHMENT 1KEY DATA ELEMENTS FOR INCLUSION IN EXPEDITEDREPORTS OF SERIOUS ADVERSE DRUG REACTIONSThe following list of items has its foundation in several established precedents, including those of CIOMS-I, the WHO International Drug Monitoring Centre, and various regulatory authority forms and guidelines. Some items may not be relevant depending on the circumstances. The minimum information required for expedited reporting purposes is: an identifiable patient, the name of a suspect medicinal product, an identifiable reporting source, and an event or outcome that can be identified as serious and unexpected and for which, in clinical investigation cases, there is a reasonable suspected causal relationship. Attempts should be made to obtain follow-up information on as many other listed items pertinent to the case.Details1. PatientInitialsOther relevant identifier (clinical investigation number, for example)GenderAge and/or date of birthWeightHeight2. Suspected Medicinal Product(s)Brand name as reportedInternational Non-Proprietary Name (INN)Batch numberIndication(s) for which suspect medicinal product was prescribed or testedDosage form and strengthDaily dose and regimen (specify units - e.g., mg, ml, mg/kg)Route of administrationStarting date and time of dayStopping date and time, or duration of treatmentTreatment(s)3. OtherFor concomitant medicinal products (including non-prescription/OTC medicinal products) and non-medicinal product therapies, provide the same information as for the suspected product.4. Details of Suspected Adverse Drug Reaction(s)Full description of reaction(s) including body site and severity, as well as the criterion (or criteria) for regarding the report as serious should be given. In addition to a description of the reported signs and symptoms, whenever possible, attempts should be made to establish a specific diagnosis for the reaction.Start date (and time) of onset of reactionStop date (and time) or duration of reactionDechallenge and rechallenge informationSetting (e.g., hospital, out-patient clinic, home, nursing home)Outcome: information on recovery and any sequelae; what specific tests and/or treatment may have been required and their results; for a fatal outcome, cause of death and a comment on its possible relationship to the suspected reaction should be provided. Any autopsy or other post-mortem findings (including a coroner's report) should also be provided when available. Other information: anything relevant to facilitate assessment of the case, such as medical history including allergy, drug or alcohol abuse; family history; findings from special investigations.5. Details on Reporter of Event (Suspected ADR)NameAddressTelephone numberProfession (speciality)6. Administrative and Sponsor/Company DetailsSource of report: was it spontaneous, from a clinical investigation (provide details), from the literature (provide copy), other?Date event report was first received by sponsor/manufacturerCountry in which event occurredType of report filed to authorities: initial or follow-up (first, second, etc.)Name and address of sponsor/manufacturer/companyName, address, telephone number, and FAX number of contact person in reporting company or institutionIdentifying regulatory code or number for marketing authorisation dossier or clinical investigation process for the suspected product (for example IND or CTX number, NDA number)Sponsor/manufacturer's identification number for the case (this number must be the same for the initial and follow-up reports on the same case).。

  1. 1、下载文档前请自行甄别文档内容的完整性,平台不提供额外的编辑、内容补充、找答案等附加服务。
  2. 2、"仅部分预览"的文档,不可在线预览部分如存在完整性等问题,可反馈申请退款(可完整预览的文档不适用该条件!)。
  3. 3、如文档侵犯您的权益,请联系客服反馈,我们会尽快为您处理(人工客服工作时间:9:00-18:30)。

a r X i v :m a t h /9704219v 3 [m a t h .C V ] 3 F eb 2004EXTENSION PROPERTIES OF MEROMORPHIC MAPPINGS WITHV ALUES IN NON-K ¨AHLER COMPLEX MANIFOLDSS.Ivashkovich*0.Introduction.0.1.Statement of the main result.Denote by ∆(r )the disk of radius r in C ,∆:=∆(1),and for 0<r <1denote by A (r,1):=∆\¯∆(r )an annulus in C .∆n (r )denotes the polydisk of radius r in C n and ∆n :=∆n (1).Let X be a compact complex manifold and consider a meromorphic mapping f from the ring domain ∆n ×A (r,1)into X .In this paper we shall study the following Question.Suppose we know that for some non-empty open subset U ⊂∆n our map f extends onto U ×∆.What is the maximal ˆU ⊃U such that f extends meromorphically onto ˆU ×∆?This is the so called Hartogs-type extension problem.If ˆU =∆n for any f with values in our X and any initial (non-empty!)U then one says that the Hartogs-type extension theorem holds for meromorphic mappings into this X .For X =C ,i.e.,for holomorphic functions the Hartogs-type extension theorem was proved by F.Hartogs in [Ha].If X =CP 1,i.e.,for meromorphic functions the result is due to E.Levi,see [Lv].Since then the Hartogs-type extension theorem has been proved in at least two essentially more general cases than just holomorphic or meromorphic ly for mappings into K¨a hler manifolds and into manifolds carrying complete Hermitian metrics of non-positive holomorphic sectional curvature,see [Gr],[Iv-3],[Si-2],[Sh-1].The goal of this paper is to initiate the systematic study of extension properties of meromorphic mappings with values in non-K¨a hler complex manifolds.Let h be some Hermitian metric on a complex manifold X and let ωh be the associated (1,1)-form.We call ωh (and h itself)pluriclosed or dd c -closed if dd c ωh =0.In the sequel we shall not distinguish between Hermitian metrics and their associated forms.The latters we shall call simply metric forms.Let A be a subset of ∆n +1of Hausdorff(2n −1)-dimensional measure zero.Take a point a ∈A and a complex two-dimensional plane P ∋a such that P ∩A is of zero length.A sphere S 3={x ∈P : x −a =ε}with εsmall will be called a ”transversal sphere”if in addition S 3∩A =∅.Take a non-empty open U ⊂∆n and set H n +1U (r )=∆n ×A (r,1)∪U ×∆.We call this set the Hartogs figure over U .Main Theorem.Let f :H n +1U (r )→X be a meromorphic map into a compact complex manifold X ,which admits a Hermitian metric h ,such that the associated (1,1)-form ωh is dd c -closed.Then f extends to a meromorphic map ˆf:∆n +1\A →X ,where A is a complete (n −1)-polar,closed subset of ∆n +1of Hausdorff(2n −1)-dimensional measure zero.Moreover,if A is the minimal closed subset such that f extends onto ∆n +1\A and A =∅,then for every transversal sphere S 3⊂∆n +1\A its image f (S 3)is not homologous to zero in X .Remarks 1.A (two-dimensional)spherical shell in a complex manifold X is the image Σof the standard sphere S 3⊂C 2under a holomorphic map of some neighborhood of S 3into X such that Σis not homologous to zero in X .Main Theorem states that if the singularity set A of our map f is non-empty,then X contains spherical shells.2.If again A =∅then,because A ∩H n +1U (r )=∅the restriction π|A :A →∆n of the natural projection π:∆n +1→∆n onto A is proper.Therefore π(A )is (n −1)-polar subset in ∆n of zero (2n −1)-dimensional measure.So,returning to our question,we see that ˆUis equal to ∆n minus a ”thin”set.We shall give a considerable number fo examples illustrating results of this paper.Let us mention few of them.Examples.1.Let X be the Hopf surface X =(C 2\{0})/(z ∼2z )and f :C 2\{0}→X be the canonical projection.The (1,1)-form ω=i z 2is well defined on X and dd c ω=0.In this example one easily sees that f is not extendable to zero and that the image of the unit sphere from C 2is not homologous to zero in X .Note also that dd c f ∗ω=dd c ω=−c 4δ{0}dz ∧d ¯z ,where c 4is the volume of the unit ball in C 2and δ{0}is the delta-fuction.2.In §3.6we construct Example 3.7of a 4-dimensional compact complex manifold X and a holomoprhic mapping f :B 2\{a k }→X ,where {a k }is a sequence of points converging to zero,such that f cannot be meromorphically extended to the neighborhood of any a k .3.We also construct an Example 3.6where the singularity set A is of Cantor-type and pluripolar.This shows that the type of singularities described in our Main Theorem may occur.At the same time it should be noticed that we don’t know if this X can be endowed with a pluriclosed metric.4.Consider now the Hopf three-fold X =(C 3\{0})/(z ∼2z ).The analogous metric form ω=i z 2is not longer pluriclosed but only plurinegative (i.e.dd c ω≤0).Moreover,if we consider ωas a bidimension (2,2)current,then it will provide us a natural obstruction for the existence of a pluriclosed metric form on X .Natural projection f :C 3\{0}→X has singularity of codimension three and X doesn’t contains spherical shells of dimension two (but contain a spherical shell of dimension three).We also prove the Hartogs-type extension result for mappings into (reduced,normal)complex spaces with dd c -negative metric forms,see Theorem 2.2.More examples,which are usefull for the understanding of the extension properties of meromorphic mappings into non-K¨a hler manifolds are given in the last paragraph.There also a general Conjecture is formulated.All compact complex surfaces admit pluriclosed Hermitian metric forms.Therefore we haveCorollary1.If X is a compact complex surface,then:(a)every meromorphic map f:H n+1U (r)→X extends onto∆n+1\A,where A is ananalytic set of pure codimension two;(b)ifΩis a Stein surface and K⋐Ωis a compact with connected complement,then every meromorphic map f:Ω\K→X extends ontoΩ\{finite set}.If this set is not empty (respectively,if A from(a)is non-empty),then X is of class VII in the Enriques-Kodaira classification;(c)if f:Ω\K→X is as in(b)butΩof dimension at least three,then f extends onto the wholeΩ.Remarks1.The fact that in the case of surfaces A is a genuie analytic subset of pure codimension two requires some additional(not complicated)considerations and is given in §3.4,where also some other cases when A can be proved to be analytic are discussed. 2.A wide class of complex manifolds without spherical shells is for example the class of such manifolds X that the Hurewicz homomorphismπ3(X)→H3(X,Z)is trivial.3.Main Theorem was proved in[Iv-2]under an additional(very restrictive)assumption: the manifold X doesn’t contain rational curves.In this case meromorphic maps into X are holomorphic.Also in[Iv-2]nothing was proved about the structure of the singular set A.4.There is a hope that the surfaces with spherical shells could be classified,as well as surfaces containing at least one rational curve.Therefore the following somewhat suprising speculation,which immediately follows from Corollary1,could be of some interest: Corollary 2.If a compact complex surface X is not”among the known ones”then for every domain D in a Stein surface every meromorphic mapping f:D→X is in fact holomorphic and extends as a holomorphic mappingˆf:ˆD→X of the envelope of holomorphyˆD of D into X.At this point let us note that the notion of a sphericall shell,as we understand it here, is different from the notion of global spherical shell from[Ka-1].5.A real two-formωon a complex manifold X is said to”tame”the complex structure J if for any non-zero tangent vector v∈T X we haveω(v,Jv)>0.This is equivalent to the property that the(1,1)-componentω1,1ofωis strictly plex manifolds admitting a closed form,which tames the complex structure,are of special interest.The class of such manifolds contains all K¨a hler manifolds.On the other hand,such metric forms are dd c-closed.Indeed,ifω=ω2,0+ω1,1+¯ω2,0and dω=0,then∂ω1,1=−¯∂ω2,0. Therefore dd cω1,1=2i∂¯∂ω1,1=0.So the Main Theorem applies to meromorphic mappings into such manifolds.In fact,the technique of the proof gives more:Corollary 3.Suppose that a compact complex manifold X admits a strictly positive (1,1)-form,which is the(1,1)-component of a closed form.Then every meromorphic mapf:H n+1U(r)→X extends onto∆n+1.This statement generalizes the Hartogs-type extension theorem for meromorphic map-pings into K¨a hler manifolds from[Iv-3],but this generalization cannot be obtained by themethods of [Iv-3]and result from [Si-2]involved there.The reason is simply that the up-per levels of Lelong numbers of pluriclosed (i.e.,dd c -closed)currents are no longer analytic (also integration by parts for dd c -closed forms doesn’t work as well as for d -closed ones).It is also natural to consider the extension of meromorphic mappings from singular spaces.This is equivalent to considering multivalued meromorphic correspondences from smooth domains,and this reduces to singlevalued maps into symmetric powers of the image space,see §3for details.However,one pays a price for these reductions.In this direction we construct in §3Example 3.5,which shows that a manifold possessing the Hartogs extension property for singlevalued mappings may not possess it for multivalued ones.The reason is that Sym 2(X )may contain a spherical shell,if even X contains none.0.2.Sketch of the proof.Let us give a brief outline of the proof of the main theorem.We first consider the case of dimension two,i.e.,n =1.For z ∈∆set ∆z :={z }×∆.For a meromorphic map f :H 2U (r )→(X,ω)denote by a (z )=area ωf (∆z )= ∆f |∗∆z ω-the area of the image of the disk ∆z .This is well defined for z ∈U after shrinking A (r,1)if necessary.Step ing dd c -closedness of ω(and therefore of f ∗ω)we show that for ”almost every”sequence {z n }⊂U converging to the boundary,areas a (z n )are uniformly bounded and converge to the area of f (∆z ∞),here z ∞∈∂U ∩∆is the limit of {z n }.This means in particular that f z ∞:=f |{z ∞}×A (r,1)extends onto ∆z ∞.And then we show that f can be extended holomorphically onto V ×∆,where V is a neighborhood of z ∞.Therefore if ˆU is the maximal open set s.t.f can be extended onto H 2ˆU (r ),then ∂ˆU ∩∆should be ”small”.In fact we show that ∂ˆU∩∆is of harmonic measure zero,see Lemmas 2.3,2.4.Step 2.Interchanging coordinates in C 2and repeating the Step 1we see that f holomor-phically extends onto ∆2\(S 1×S 2),where S 1and S 2are compacts (after shrinking)of harmonic measure zero.We can use shrinkung here,because subsets of harmonic measure zero in C are of Hausdorffdimension zero.Set S =S 1×S 2.Smooth form T :=f ∗ωon ∆2\S has coefficients in L 1loc (∆2)and therefore has trivial extension ˜T onto ∆2,see Lemma 3.3form [Iv-2]and Lemma 2.1.We prove that µ:=dd c ˜Tis a non-positive measure supported on S .Step 3.Take a point s 0∈S and,using the fact that S is of Hausdorffdimension zero,take a small ball B centered at s 0such that ∂B ∩S =∅.Now we have two possibilities.First:f (∂B )is not homologous to zero in X .Then ∂B represent a spherical shell in X ,as it was said in the remark after the Main Theorem.Second:f (∂B )∼0in X .Then we can prove,see Lemmas 2.5,2.8that ˜T is dd c -closed and consequently it be written in the form ˜T =i (∂¯γ−¯∂γ),where γis some (0,1)-current on B ,which is smooth on B \S .This allows to estimate the area function a (z )in the neighborhood of s 0and extend f .Step 4.We consider now the case n ≥2.Using case n =1by sections we extend f onto ∆n +1\A where A is complete pluripolar of Hausdorffcodimension four.Then take a transversal to A at point a ∈A complex two-dimensional direction and decompose the neighborhood W of a as W =B n −1×B 2,where A ∩(B n −1×∂B 2)=∅.If f ({a }×∂B 2)is homologous to zero then we can repeat Step 3”with parameters”.This will give a uniform bound of the volume of the two-dimensionalsections of the graph of f.Now we are in position ty apply the Lemma1.3(which is another main ingredient of this paper)to extend f onto W.Remark.We want tofinish this Introduction with a brief account of existing methods of extension of meromorphic mappings.The First method,based on Bishop’s extension theorem for analytic sets(appearing here as the graphs of mappings)and clever integration by parts was introduced by P.Griffiths in[Gr],developed by B.Shiffman in[Sh-2]and substantially enforced by Y.-T.Siu in[Si-2](where the Thullen-type extension theorem is proved for mappings into K¨a hler manifolds),using his celebrated result on the analyticity of upper level sets of Lelong numbers of closed positive currents.The latter was by the way inspired by the extension theorem just mentioned.Finally,in[Iv-3]the Hartogs-type extendibility for the mappings into K¨a hler manifolds was proved using the result of Siu and a somewhat generalized classical method of”analytic disks”.This method works well for mappings into K¨a hler manifolds.The Second method,based on the Hironaka imbedded resolution of singularities and lower estimates of Lelong numbers was proposed in[Iv-4]together with an example showing the principal difference between K¨a hler and non-K¨a hler cases.This method implies the Main Theorem of this paper for n=1,2(this was not stated in[Iv-4]).However,further increasing of n meets technical difficulties at least on the level of the full and detailed proof of Hironaka’s theorem(plus it should be accomplished with the detailed lower estimates of the Lelong numbers by blowings-up).The Third method is therefore proposed in this paper and is based on the Barlet cycle space theory.It gives definitely stronger and more general results than the previous two and is basically much more simple.Key point is Lemma1.3from§1.An important ingredient of last two methods is the notion of meromorphic family of analytic subsets and especially Lemma2.4.1from[Iv-4]about such families.The reader is therefore supposed to be familiar with§§2.3and2.4of[Iv-4]while reading proofs of both Lemma1.3and Main Theorem.I would like to give my thanks to the refery,who pointed to me a gap in the proof of the analyticity of the singular set.Table of content0.Introduction................................pp.1-51.Meromorphic mappings and cycle spaces......pp.5-142.Hartogs-type extension and spherical shells...pp.14-253.Examples and open questions...............pp.25-34 References.................................pp.34-371.Meromorphic mappings and cycle spaces.1.1.Cycle space associated to a meromorphic map.We shall freely use the results from the theory of cycle spaces developed by D.Barlet, see[Ba-1].For the English spelling of Barlet’s terminology we refer to[Fj].Recall that ananalytic k -cycle in a complex space Y is a formal sum Z = j n j Z j ,where {Z j }is a locally finite sequence of analytic subsets (always of pure dimension k )and n j are positive integerscalled multiplicities of Z j .Let |Z |:= j Z j be the support of Z .All complex spaces in this paper are reduced,normal and countable at infinity.All cycles,if the opposite is not stated,are supposed to have connected support.Set A k (r,1)=∆k \¯∆k (r ).Let X be a normal,reduced complex space equipped with some Hermitian metric.Let a holomorphic mapping f :¯∆n ׯA k (r,1)→X be given.We shall start with the following space of cycles related to f .Fix some positive constant C and consider the set C f,C of all analytic k -cycles Z in Y :=∆n +k ×X such that:(a)Z ∩[∆n ׯA k (r,1)×X ]=Γf z ∩[¯A k z (r,1)×X ]for some z ∈∆n ,where Γf z is the graph of the restriction f z :=f |A k z (r,1).Here A k z (r,1):={z }×A k (r,1).This means,in particular,that for this z the mapping f z extends meromorphically from ¯A k z (r,1)onto ¯∆k z :={z }ׯ∆k .(b)vol (Z )<C and the support |Z |of Z is connected.We put C f := C>0C f,C and we are going to show that C f is an analytic space of finite dimension in a neighborhood of each of its points.Let Z be an analytic cycle of dimension k in a (reduced,normal)complex space Y .In our applications Y will be ∆n +k ×X .By a coordinate chart adapted to Z we shall understand an open set V in Y such that V ∩|Z |=∅together with an isomorphism j of V onto a closed subvariety ˜Vin the neighborhood of ¯∆k ׯ∆q such that j −1(¯∆k ×∂∆q )∩|Z |=∅.We shall denote such a chart by (V,j ).The image j (Z )of cycle Z under isomorphism j is the image of the underlying analytic set together with multiplicities.Sometimes we shall,following Barlet,denote:∆k =U,∆q =B and call the quadruple E =(V,j,U,B )a scale adapted to Z .If pr :C k ×C q →C k is the natural projection,then the restriction pr |j (Z ):j (Z )→∆k is a branched covering of degree say d .The number q depends on the imbedding dimension of Y (or X in our case).Sometimes we shall skip j in our notations.The branched covering pr |Z :Z ∩(∆k ×∆q )→∆k defines in a natural way a mapping φZ :∆k →Sym d (∆q )-the d -th symmetric power of ∆q -by setting φZ (z )=(pr |Z )−1(z ).This allows to represent a cycle Z ∩∆k +q with |Z |∩(¯∆k ×∂∆q )=∅as the graph of a d -valued holomorphic map.Without loss of generality we suppose that our holomorphic mapping f is defined on ∆n (a )×A k (r 1,b )with a,b >1,r 1<r .Now,each Z ∈C f can be covered by a finite number of adapted neighborhoods (V α,j α).Such covering we be called an adapted covering.Denote the union αV αby W Z .Taking this covering {(V α,j α){to be small enough,we can further suppose that:(c)if V α1∩V α2=∅,then on every irreducible component of the intersection Z ∩V α1∩V α2a point x 1is fixed so that:(c 1)either there exists a polycylindric neighborhood ∆k 1⊂∆k of pr (j α1(x 1))such that the chart V 12=j −1α1(∆k 1×∆q )is adapted to Z and is contained in V α2,where V 12is given the same imbedding j α1,(c 2)or this is fulfilled for V α2instead of V α1;(d)if V α∋y with p (y )∈¯∆n (c )×A k (r +12)×A k (r,1).Here we denote by p :∆n +k ×X →∆n +k the natural projection.Case (c 1)can berealized when the imbedding dimension of V α1is smaller or equal to that of V α2,and (c 2)in the opposite case,see [Ba-1],pp.91-92.Let E =(V,j,U,B )be a scale on the complex space Y .Denote by H Y (¯U,sym d (B )):=Hol Y (¯U,sym d (B ))the Banach analytic set of all d -sheeted analytic subsets on ¯U ×B ,contained in j (Y ).The subsets W Z together with the topology of uniform convergence on H Y (¯U,sym d (B ))define a (metrizable)topology on our cycle space C f ,which is equivalent to the topology of currents,see [Fj],[H-S].We refer the reader to [Ba-1]for the definition of the isotropicity of the family of elements from H Y (¯U,sym d (B ))parametrized by some Banach analytic set S .Space H Y (¯U,sym d (B ))can be endowed by another (more rich)analytic structure.This new analytic space will be denoted by ˆH Y (¯U,sym d (B )).The crucial property of this new structure is that the tautological family ˆH Y (¯U,sym d (B ))×U ′→sym d (B )is isotropic in H Y (¯U′,sym d (B ))for any relatively compact polydisk U ′⋐U ,see [Ba-1].In fact for isotropic families {Z s :s ∈S}parametrized by Banach analytic sets the following Projec-tion Changing theorem of Barlet holds.Theorem (Barlet).If the family {Z s :s ∈S}⊂H Y (¯U,sym d (B ))is isotropic,then for any scale E 1=(V 1,j 1,U 1,B 1)in U ×B adapted to some Z s 0,there exists a neighborhood U s 0of s 0in S such that {Z s :s ∈U s 0}is again isotropic in V 1.This means,in particular,that the mapping s →Z s ∩V 1⊂H Y (¯U1,sym d (B 1))is analytic,i.e.,can be extended to a neighborhood of any s ∈U s 0.Neighborhood means here a neighborhood in some complex Banach space where S is defined as an analytic subset.This leads naturally to the followingDefinition 1.1.A family Z of analytic cycles in an open set W ⊂Y ,parametrized by a Banach analytic space S ,is called analytic in a neighborhood of s 0∈S if for any scale E adapted to Z s 0there exists a neighborhood U ∋s 0such that the family {Z s :s ∈U }is isotropic.1.2.Analyticity of C f and construction of G f .Let f :¯∆n ׯA k (r,1)→X be our map.Take a cycle Z ∈C f and a finite covering (V α,j α)satisfying conditions (c)and (d).As above,put W Z = V α.We want to shownow that C f is an analytic space of finite dimension in a neighborhood of Z .We divide V α’s into two types.Type 1.These are V αas in (d).For them putH α:= z{[Γf z ∩¯A k z(r,1)×X ]∩V α}⊂H Y (¯U α,Sym d α(B α)).(1.2.1)The union is taken over all z ∈∆n such that V αis adapted to Γf z .Type 2.These are all others.For V αof this type we put H α:=ˆHY (¯U α,Sym d α(B α)).All H αare open sets in complex Banach analytic subsets and for V αof the first type they are of dimension n and smooth.The latter follows from Barlet-Mazet theorem,which tells that if h :A →S is a holomorphic injection of a finite dimensional analytic set A into a Banach analytic set S ,then h (A )is also an Banach analytic set of finite dimension,see[Mz].For every irreducible component of Vα∩Vβ∩Z l wefix a point xαβl on this component (the subscript l indicates the component),and a chart Vα∩Vβ⊃(Vαβl,φαβl)∋xαβl adapted to this component as in(c).Put Hαβl:=ˆH(∆k,Sym dαβl(∆p)).In the sequel it will be convenient to introduce an order on ourfinite covering{Vα}and write{Vα}Nα=1.Considerfinite productsΠ(α)HαandΠ(αβl)Hαβl.In the second product we take only triples withα<β.These are Banach analytic spaces and by the Projection Changing Theorem of Barlet,for each pairα<βwe have two holomorphic mappingsΦαβ:Hα→Π(l)H(αβl)andΨαβ:Hβ→Π(l)Hαβl.This defines two holomorphic mapsΦ,Ψ:Π(α)Hα→Πα<β,l Hαβl.The kernel A of this pair,i.e.,the set of h={hα}withΦ(h)=Ψ(h),consists exactly from analytic cycles in the neighborhood W Z of Z.This kernel is a Banach analytic set,and moreover the family A is an analytic family in W Z in the sense of Definition1.1. Lemma1.1.A is offinite dimension.Proof.Take a smaller covering{V′α,jα}of ly,V′α=Vαfor Vαof thefirst type and V′α=j−1α(∆1−ε×∆p)for the second.In the same manner define H′αand H′:=ΠαH′α. Repeating the same construction as above we obtain a Banach analytic set A′.We have a holomorphic mapping K:A→A′defined by the restrictions.The differential dK≡K of this map is a compact operator.Let us show that we also have an inverse analytic map F:A′→A.The analyticity of F means more precisely that it should be defined in some neighborhood of A′in H′.For scales Eα=(Vα,Uα,Bα,jα)of the second type the mapping Fα:A′→H Y(¯Uα,Sym kαBα) is defined by the isotropicity of the family A′as in[Ba-1].In particular,this Fαextends analytically to a neighborhood in H′(!)of each point of A′.For scales Eα=(Vα,Uα=U′α,Bα,jα)of thefirst type define Fαas follows.Let Y=(Yα)be some point from H′.Using the fact that Hα=H′αin this case,we can correctly define Fα(Y):=Yαviewed as an element of Hα.This directly defines Fαon the whole H′.Analyticity is also obvious.Put F:=ΠαFα:A′→A.F is defined and analytic in a neighborhood of each point of A′.Observe further that id−dK◦dF is Fredholm.Since A′⊂{h∈Π(i)H′i: (id−K◦F)(h)=0},we obtain that A′is an analytic subset in a complex manifold of finite dimension.q.e.d.Therefore C f is an analytic space offinite dimension in a neighborhood of each of itspoints.C f,C are open subsets of C f.Note further that for C1<C2the set C f,C1is anopen subset of C f,C2.This implies that for each irreducible component K C of C f,C thereis a unique irreducible component K of C f containing K C and moreover K C is an open subset of K.Of course,in general the dimension of irreducible components of C f is not bounded,and in fact the space C f is too big.Let us denote by G f the union of irreducible components of C f that contain at least one irreducible cycle or,in other words,a cycle of the formΓfzfor some z∈∆n.Denote by Z f:={Z a:a∈C f}the universal family.In the sequel B k(X)will denote the Barlet space of compact analytic k-cycles in normal,reduced complex space X. Lemma1.2.1.Irreducible cycles form an open dense subset G0f in G f.2.The dimension of G f is not greater than n.3.If k=1,then all compact irreducible components of cycles in G f are rational. Proof.1.G0f is clearly open,this follows immediately from(4)and(6)of Lemma2.3.1in [Iv-4].Denote byˆC f the normalization of C f and denote byˆZ f the pull-back of the universal family under the normalization map N:ˆC f→C f.Consider the following”forgetting of extra compact components”mappingΠ:ˆC f→ˆC f.Note that each cycle Z∈ˆC f can be uniquely represented as Z=Γfs+ΣN j=1B j s,where each B j s is a compact analytic k-cycle in ∆k s(r)×X with connected support.Mark those B j s,which possess the following property: there is a neighborhood in V of Z inˆC f such that every cycle Z1∈V decomposes as Z1=ˆZ1+B1,where B1is a compact cycle in a neighborhood of B j s in the Barlet space B k(X).Our mappingΠ:ˆC f→ˆC f sends each cycle Z to the cycle obtained from this Z by deleting all the marked components.This is clearly an analytic map.Every irreducible cycle is clearly afixed point ofΠ.Thus the set offixed points is open inˆG f⊂ˆC f and so contains the wholeˆG f.Now we shall prove that everyfixed point Z ofΠis a limit of irreducible cycles.For the sequel remark that the compositionsψ:=p◦ev:Z f→∆n+k andφ:=p1◦ev◦π−1: C f→∆n are well defined.Here p1:∆n+k×X→∆n is one more natural projection and ev:Z f→∆n+k×X is the natural evaluation map.Letφ(Z)=s∈∆n and Z=Γfs+ΣN j=1B j s.Z being afixed point ofΠmeans that in any neighborhood of Z onecanfind a cycle Z1such that Z1=Γfs1+ΣN j=2B j s1,where B j s1are compact cycles closeto B j s.Observe that every cycle in a neighborhood of Z1has the same form,i.e.,in its decomposition j≥2,which follows from Lemma2.3.1from[Iv-4].Since Z1is also afixed point forΠ,we can repeat this procedure N times to obtainfinally an irreducible cycle in a given neighborhood of Z.We conclude that G0f is dense in G f.2.Take an irreducible Z∈G0f∩Reg(G f).Take a neighborhood Z∈V⊂Reg(G f)that consists from irreducible cycles only.Thenφ|V:V→∆n is injective and holomorphic. Thus dim G f≤n.3.This part follows from Lemma7in[Iv-5]because every cycle from G f is a limit of analytic disks.q.e.d. Definition1.2.We shall call the space G f the cycle space associated to a meromorphic map f.Denote by G f,C the open subset of G f consisting of Z with vol(Z)<C.1.3.Proof of the Main Lemma.Now we are ready to state and prove the main lemma of this paragraph,i.e.Lemma 1.3.From now on we restrict our universal family Z f onto G f withought changing nota-tions.I.e.now Z f,C:={Z a:a∈G f,C},Z f:= C>0Z f,C andπ:Z f→G f is the natural projection.Z f is a complex space offinite dimension.We have an evaluation mapev:Z f→∆n+k×X,(1.3.1) defined by Z a∈Z f→Z a⊂∆n+k×X.Evaluation map(1.3.1)will be used in the proof of the Lemma1.3.Recall that we suppose that our complex space X is equipped with some Hermitian metric h.Lemma1.3.Let a holomorphic map f:¯∆nׯA k(r,1)→X into a complex space X be given.Suppose that:1)for every z∈¯∆n the restriction f z extends meromorphically onto the whole k-disk¯∆k z ;2)the volumes of graphs of these extensions are uniformly bounded;3)there exists a compact K⋐X which contains f(¯∆nׯA k(r,1))and f(¯∆k z)for allz∈¯∆n.Then f extends meromorphically onto∆n+k.Proof.Denote byν=ν(K)the minimal volume of a compact k-dimensional analytic subset in K,ν>0by Lemma2.3.1from[Iv-4].Denote by W the maximal open subset of ∆n such that f extends meromorphically onto∆n×A k(r,1)∪W×∆k.Set S=∆n\W. LetS l={z∈S:vol(Γfz )≤l·ν。

相关文档
最新文档