Identification and control of continuous-time nonlinear systems via dynamic neural networks

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Control practices statement-DS5

Disclaimer
The IT Governance Institute (ITGI) and the authors of the IT Control Practice for DS 5 have designed the document primarily as an educational resource for control professionals. The ITGI makes no claim that use of this product will assure a successful outcome. The product should not be considered inclusive of any proper procedures and tests or exclusive of other procedures and tests that are reasonably directed towards obtaining the same results. In determining the propriety of any specific procedure or test, the controls professional should apply his or her own professional judgment to the specific control circumstances presented by the particular systems or information technology environment.
IT CONTROL PRACTICE STATEMENT
For the COBIT High-Level Control Objective DS 5 Ensure Systems Security

管理学控制双语

1、什么是控制? What is Control?

控制

对各项活动的监视，从而保证各项行动按计划进行并纠正各种显著偏差的过程。

Control
The management function that involves monitoring activities to ensure that they’re being accomplished as planned and correcting any significant deviations
6.
7.
Identify the contingency factors in the control process.
Describe how national differences influence the control process.
8.
Identify the ethical dilemmas in employee monitoring.
小集团控制 Clan control

小集团控制 -员工的行为靠共同的价值、规范、传
统、仪式、信念及其他组织文化方面的东西来调节

基于个体和群体（或小集团）来辨别适当的和期望的行为及其衡量方法在团体合作频繁且技术变化剧烈的公司中出现
Clan control emphasizes that employee behaviors are regulated by the shared values, norms, traditions, rituals, beliefs, and other aspects of the organization’s culture.

管理学英语试题及答案

管理学英语试题及答案一、选择题（每题2分，共20分）1. The term "management" refers to the process of:A. Making decisionsB. Organizing resourcesC. Directing and controlling activitiesD. All of the above答案：D2. Which of the following is NOT a function of management?A. PlanningB. StaffingC. MotivatingD. Selling答案：D3. The process of setting goals and deciding on actions to achieve these goals is known as:A. OrganizingB. LeadingC. PlanningD. Controlling答案：C4. Which of the following is an example of a managementprinciple?A. Division of laborB. CentralizationC. DelegationD. All of the above答案：D5. In the context of management, "controlling" refers to:A. The process of ensuring that things are done as plannedB. The process of making plansC. The process of organizing resourcesD. The process of motivating employees答案：A6. The concept of "span of control" is related to:A. The number of employees a manager can effectively superviseB. The range of activities a manager is responsible forC. The level of authority a manager hasD. The type of control systems a manager uses答案：A7. The management function that involves influencing people to work towards organizational goals is:A. OrganizingB. LeadingC. PlanningD. Controlling答案：B8. Which of the following is a characteristic of effective communication?A. ClarityB. AmbiguityC. DisorganizationD. Lack of feedback答案：A9. The "scientific management" theory was developed by:A. Henri FayolB. Max WeberC. Frederick TaylorD. Abraham Maslow答案：C10. In the context of management, "empowerment" means:A. Giving employees the authority to make decisionsB. Centralizing all decision-making powerC. Reducing the role of employees in decision-makingD. Ignoring employee input in decision-making答案：A二、填空题（每题1分，共10分）1. The four basic functions of management are planning, organizing, leading, and ________.答案：controlling2. The management principle that suggests that there is an optimal span of control for each manager is known as ________.答案：span of control3. The management approach that focuses on the social needsof employees is known as the ________ approach.答案：human relations4. The process of identifying, selecting, orienting, training, and compensating employees is known as ________.答案：staffing5. A management style that involves a high level of task orientation and a low level of relationship orientation is known as ________ leadership.答案：autocratic6. The concept of "management by objectives" was developed by ________.答案：Peter Drucker7. The "Maslow's hierarchy of needs" theory suggests that people are motivated by a series of needs, starting with physiological needs and ending with ________ needs.答案：self-actualization8. In a ________ structure, there is a clear chain of command and a narrow span of control.答案：hierarchical9. The process of comparing actual performance with planned performance is known as ________.答案：budgeting10. The management function that involves setting goals and determining the sequence of actions needed to achieve them is known as ________.答案：strategic planning三、简答题（每题5分，共30分）1. What are the three key characteristics of an effective organizational structure?答案：An effective organizational structure should havethe following characteristics: clarity of roles and responsibilities, a clear chain of command, and a balance between centralization and decentralization.2. Explain the difference between leadership and management.答案：Leadership is the process of influencing, motivating, and directing individuals towards the achievement of organizational goals. Management, on the other hand, is a broader concept that includes planning, organizing, leading, and controlling organizational resources to achieve goals.3. What are the main principles of scientific management according to Frederick Taylor?答案：The main principles of scientific management includethe scientific selection and training of workers, the scientific selection of tasks and tools, the scientific determination of work methods, and the scientific scheduling of work and rest periods.4. Describe the four stages of the control process.。

The Use of Ion Chromatography for the Determination of Clean-In-Place-200 (CIP-200) Detergent Traces

ORIGINAL RESEARCHCorrespondence: Dr. José Zayas, Research and Development Division, ZAYCOR Industries Corporation, 28 de Diego Ave. Caparra Terrace , San Juan PR 00921. HYPERLINK “”;Tel: 787-999-3016; Fax: 787-999-8981; Email: jzayas@The Use of Ion Chromatography for the Determination of Clean-In-Place-200 (CIP-200) Detergent TracesWilfredo Resto 1, Joan Roque 1, Rosamil Rey 2,3, Héctor Colón 2, and José Zayas 21Department of Chemistry University of Puerto Rico-Cayey, Antonio R. Barceló Ave.Cayey P.R. 00736. 2Research and Development Division, ZAYCOR Industries Corporation, 828 de Diego Ave. Caparra Terrace, San Juan PR 00921. 3Interamerican University, Bayamón Campus, Department of Natural Sciences, Bayamon, Puerto Rico 00957.Abstract: Anion chromatography with conductivity detection was chosen as the analytical technique for the development of a cleaning validation method for clean-in-place (CIP) detergents. The method was developed and validated for the de-termination of traces of the detergent CIP-200. It was shown to be linear with a squared correlation coef ﬁ cient (r 2) of 0.9999 and the accuracy experiments presented average recoveries of 88.2% (area response factor) from stainless steel surfaces. The repeatability was found to be 1.6% and an intermediate precision of 1.9% across the range. The method was also shown to be sensitive with an average Detection Limit (DL) of 0.23 ppm and a Quantitation Limit (QL) of 0.70 ppm based on the amount of phosphate in the detergent sample. The phosphate signal was well resolved from typical ions encountered in water samples or any other interference presented from swabs and surfaces. The method was applied to cleaning validation samples and proved to be suitable for rapid and reliable quality control.Keywords: cleaning validation, ion chromatography, CIP detergent, phosphate analysis.Introduction Ion chromatography (IC) is one of the most employed chromatographic methods nowadays in Industry. Within the different methods included under Ion Chromatography, anion chromatography presents the most popular due to its simplicity, sensitivity and selectivity (Lucy, 1996; Sarzanini, 2001). Anion chromatography can be performed with or without suppression, however, suppressed methods are the most widely used. Reviews on the basic theory and recent advances of IC have been published and the reader is encouraged to read those references for detailed description of the technique as well as the advances related to it (Lucy, 1996; Sarzanini, 2001). When suppressed methods are employed the eluents commonly used are either carbonate or hydroxide. In the technique, a device known as a suppressor is placed between the column and the detector. With suppression methods, the detection system is based in conductivity. The basis of suppression is the reduction of the background conductivity, while the sensitivity of the anion is increased. The suppres-sion system that takes place in anion chromatography is a cation exchanger that exchanges cations with H + ions. For example, an eluent made of sodium carbonate having a conductivity of ~ 800 µS is converted in the suppression process to carbonic acid which has a conductivity of ~ 18 µS. However, an analyte made of NaCl with a conductivity of ~ 126 µS without suppression, would become HCl with a conduc-tivity of ~ 426 µS when suppression takes place.For many chromatographers, ion chromatography advances departed with the report by Small in 1975. In this report, Small introduced the use of low capacity stationary phases with suppressed conduc-tivity. (Small, Stevens, and Bauman, 1975) Since then, Anion chromatography has found its niche in the analysis of many substances in many different areas. The ﬁ rst standard method for anion chroma-tography was established for analysis of anions in water samples in 1984. (ASTM, 1984) Since then, many authors have reported on the use of ion chromatography for the determination of anions.( Jackson and Pohl, 1997; Roig-Navarro, Martínez-Bravo, López et al. 2001; Vanatta and Coleman, 2001.)When analyzing CIP systems, the characterization of such analytes can be troublesome. The basic reason is that the ratio of components is approximated to percentages ranging from 5 to 20% of eachZayas et alcomponent, as provided by the manufacturer in the MSDS of the cleaning products. Therefore, it is very difﬁ cult to attain the right amount for each component. Other methods of analysis include complexation reactions to produce a chromophore suitable for UV detection. This method, is the most common one for the analysis of CIP’s detergents, however, the extra step of the complexation reac-tion adds the possibility of errors in the analysis. The use of non speciﬁ c methods such as total organic carbon (TOC) would provide the amount of carbon present in the sample. This amount of carbon however will not necessarily come from the detergent and possible contaminants different than the detergent could be attributed to the pres-ence of the CIP-200. Besides, the exact amount of carbon in the detergent is not known because the amounts of the surfactants used are also reported as a range.Our laboratory has investigated on ways to analyze CIP detergents for cleaning validation purposes. A healthy cleaning validation program should assure lower levels of cross contamination with products or detergents. The Food and Drug Administration (FDA) enforces those cleaning processes and the Agency published guides where they speciﬁ ed that no detergent should remain after the cleaning process.(FDA, 1993; 2000)In the present work, we report on the develop-ment of a cleaning validation method for the analysis of CIP-200 using the phosphate ion as the analyte to determine traces amounts of the deter-gent in stainless steel plates. All the parameters required by ICH for the validation of such method were taken into consideration.ExperimentalEquipmentThe IC system consisted of a Metrohm-peak 761 compact Ion Chromatography system (Herisau, Switzerland) with conductivity detection and a computer with ICNet 2.1 computer software for data handling.Materials and reagentsAll solvents used were of HPLC and analytical-reagent grade. Water used for mobile phase, sample and standards preparations was obtained from a Barnstead NanoPure (Dubuque, Iowa, U.S.A) system without further puriﬁ cation. The certiﬁ ed ACS sodium bicarbonate was obtained from Fisher (Fair Lawn, NJ, U.S.A), the sodium carbonate was obtained J.T. Baker (Philipsburg, NJ, U.S.A), and the Sodium Phosphate was obtained from Sigma (St. Louis, MO). Stainless steel plates were 25 × 25 mm dimensions, made out of stainless steel 304 un-polished material. The CIP-200 detergent was supplied by the Steris Corporation, lot 216811 (St. Louis, MO, U.S.A).Chromatographic conditionsThe column used was a Metrohm-Peak Metrosep A Supp 5–150, polyvinyl alcohol with quaternary ammonium groups, 5 µm, and 4.0 mm × 150 mm with a mobile phase composed of sodium carbonate: sodium hydrogen carbonate (3.2 mM: 1.0 mM), ﬂ ow rate of 0.7 mL/min. The injection volume used was 20 µL. The chromatographic experiments were run at room temperature (20 °C).Mobile phase preparationThe sodium carbonate: sodium hydrogen carbonate (4.5 mM: 1.0 mM) mobile phase was prepared by weighing 0.48 g of sodium carbonate and 0.097 g of sodium hydrogen carbonate dissolved them with deionized water and transferred to a 1.00 L volu-metric ﬂ ask and diluted to volume with deionized water. The mixture was properly filtered and degassed. This solution was used as the mobile phase, diluent for the phosphate standards and CIP-200 working samples, and also as the extracting solution.Preparation of the phosphate standardsThe phosphate stock standard solution was prepared by weighing 0.0971 g Na3PO4 dissolved in deion-ized water and transferred to a 100.00 mL volu-metric ﬂ ask and diluted to volume with deionized water. The phosphate working solution was prepared by pipetting 5.00 mL of the stock solution into a 50.00 mL volumetric ﬂ ask and diluted to volume with mobile phase. The resulting concentra-tion for the phosphate anion in the stock standard solution and the working solutions were 562 ppm and 56.2 ppm respectively. From the working solu-tion different aliquots were taken and diluted to volume with the sodium carbonate: sodium hydrogen carbonate (4.5 mM: 1.0 mM) mobileDetermination of CIP200 by Ion Chromatographystainless steel plate. The procedure was repeated for each of the solutions. The metal plates were allowed to dry at room temperature. A TEXWIPE TX761 swab was deposited in a vial that contained 2.00 mL of mobile phase. For each deposited aliquot, a wet swab was passed over the surface of the plate, one side of the swab was passed hori-zontally and the other vertically. The swabbing process has been represented schematically elsewhere.(Zayas, Colón, Garced, et al. 2006) The swab was returned to a vial with 2.00 mL of mobile phase. The vials were shaken mechanically for 10 minutes and each of them analyzed by IC.Results and Discussion System suitability The ion chromatographic system suitability was evaluated according to the requirements set forth by the United States Pharmacopoeia (USP 27). (21CFR 211.67; 21CFR 211.160, United States Pharmaco-peia (USP) 2004) System precision, theoretical plates (N), and tailing factor (T) were evaluated. The system precision was obtained from the pooled relative standard deviation (co-variance, percentage of RSD pooled ) of three sets of replicate injections from different days and preparations. Each replicate set consisted of six consecutive injections. This afforded a percentage of RSD pooled value of 0.51% by area response factor and 1.1% by height response factor. The average theoretical plates resulted in N of 3900, and the tailing factor, T, was calculated at 1.1 on the average. The resolution factor R was calculated against the chlorine peak and set at 6 based on average determinations. Figure 1 displays a typical chromatogram for a system suitability run. Figure 2 displays a typical blank chromatogram.Repeatability and intermediate precision The repeatability of the method was determined by using the response factor values obtained for a set of different concentrations. The set consisted of three consecutive injections for each of the three different concentrations. These were averaged and the pooled standard deviation determined (S pooled ). These values were used to calculate the pooled percentage of RSD. This afforded a percentage of RSD pooled value of 1.1% by area response factor and 1.6% by height response factor.Table 1. Phosphate standard preparation (10.00 mL ﬁ nal volume) Aliquot of phosphate Theoretical concentration w orking solution (mL) of phosphate (ppm) 0.25 1.41 0.50 2.811.00 5.622.00 11.23.00 16.9phase. Three replicates were prepared for each off the standards solutions. The ﬁ nal concentrations of the standards solutions are presented in Table 1.Preparation of stock CIP-200 detergent solutions A 0.25 mL aliquot of a CIP-200 sample was placed in a 100.00 mL volumetric ﬂ ask and diluted to volume with deionized water. Aliquots of this stock solution were further diluted in order to reach the desired concentration for these studies. Preparation of the CIP-200 sample The sample for the determination of phosphate concentration in the CIP-200 was prepared by pipetting 0.50 mL of the CIP-200 stock solution to a 10.00 mL volumetric ﬂ ask and diluted to volume with the sodium carbonate: sodium hydrogen carbonate (4.5 mM: 1.0 mM) mobile phase. From this solution 1.00 mL were pipetted into a 10.00 mL volumetric ﬂ ask and diluted to volume with mobile phase. Three replicates were prepared for the CIP sample. The average phosphate concentra-tion determined for this solution was 6.74 ppm by area response factor and 6.77 ppm by height response factor.Preparation for the recovery of CIP-200 from stainless steel surface The solutions used for recovery from plate were prepared using aliquots from the CIP-200 stock solution. Aliquots of 2.00 mL, 2.50 mL, and 3.00 mL were pipetted to 25.00 mL volumetric ﬂ asks and diluted to volume with the sodium carbonate: sodium hydrogen carbonate (4.5 mM: 1.0 mM) mobile phase. From the determination of the CIP-200 sample the resulting concentrations for these solutions were 108 ppm, 135 ppm, and 162 ppm respectively. A volume of 100 µL for each of these solutions was spread over a clean and dry 2" × 2"Zayas et alFigure 1. Typical system suitability chromatogram of the Phosphate Standard. Suitability ran at room temperature at 0.7 mL/min. Na 2CO 3-NaHCO 3: 4.5 mM: 1.0 mM. Conductivity detection.Figure 2. Typical blank chromatogram. Ran at room temperature at 0.7 mL/min. Na 2CO 3-NaHCO 3: 4.5 mM: 1.0 mM. Conductivity detection.Determination of CIP200 by Ion ChromatographyThe intermediate precision of the method was determined by using the response factor values for a set of different concentrations prepared by different analysts on the same day and by the same analyst on different days. Each set consisted of three consecutive injections for each of the three different concentrations. These were averaged and the pooled standard deviation determined (S pooled ). The values were used to calculate the pooled percentage of RSD. This afforded a percentage of RSD pooled value of 1.9% by area response factor and 2.1% by height response factor. Table 2 shows the pooled chromato-graphic data used for the calculations. Ruggedness The ruggedness was demonstrated by comparing the recovery from the plate for two different preparations by two different analysts. The statis-tical calculations are explained elsewhere. (Zayas, Colón, Garced et al. 2006) From the results it can be concluded that the method is rugged enough to allow two different analysts to work on the deter-mination of phosphate in CIP-200 without signif-icant statistical differences.Linearity The linearity of the method was established by calculating the linear regression of multiple determinations at a concentration range from 1.41 ppm to 16.83 ppm of phosphate standards. The data was combined to determine the linearity of the method. The calibration curve showed a sensitivity of 4.49 (µS/cms)/ppm with correlation coef ﬁ cient of 0.9999 for the area response factor and sensitivity of 0.308 (µS/cm)/ppm with a correlation coef ﬁ cient of 0.9993 for the height response factor. The method demonstrated outstanding linearity over the concen-tration range analyzed. The data of the calibration curve of phosphate standards and the CIP-200 phos-phate determination is shown in Table 3. Figure 3 presents a stacked arrangement of the typical chro-matograms of the phosphate standards.Limit tests The detection limit (DL) and the quantitation limit (QL) were determined from the calibration curve of 5 different phosphate standard concentrations. The ICH guide (ICH, 1996) recommends as an alternative for the estimation of the Detection (DL) and Quantitation (QL) limits the following equation:S/N Estimate = Sxy/SlopeWhere S/N Estimate is the approximation of the signal-to-noise ratio (semi-empirical), Sxy is the Table 2. Pooled Chromatographic Data to Asses Intermediate Precision.Standard Average Pooled Pooled Average Pooled Pooled Concentration Area Standard RSD% Height Standard RSD%(ppm) (µS/cms) Deviation (µS/cm) Deviation(µS/cms) (µS/cm)2.81 14.225 0.533.76 0.799 0.12 15.135.62 29.329 0.49 1.68 1.660 0.03 1.81 11.23 60.036 1.03 1.71 3.422 0.10 2.97Table 3. Calibration Curve and CIP-200 Phosphate Chromatographic Determination Data.Standard Average Standard RSD% Average Standard RSD%Concentration Area Deviation Height Deviation(ppm) (µS/cms) (µS/cms) (µS/cm) (µS/cm)1.41 5.596 0.06 1.12 0.363 0.01 1.592.81 11.786 0.24 2.06 0.770 0.01 1.305.62 24.083 0.13 0.53 1.567 0.01 0.3711.2 49.133 0.41 0.84 3.287 0.02 0.4616.9 74.994 0.47 0.63 5.127 0.04 0.69CIP-200 Sample 29.333 0.20 0.67 1.97 0.01 0.72Zayas et alFigure 4. Typical CIP-200 chromatogram for the accuracy experiments.Chromatogram ran at room temperature at 0.7 mL/min.Na2CO3-NaHCO3: 4.5 mM: 1.0 mM.Conductivity detection.Figure 3. Typical calibration chromatograms of the phosphate standards. Ran at room temperature at 0.7 mL/min. Na2CO3-NaHCO3: 4.5mM: 1.0 mM. Conductivity detection.Determination of CIP200 by Ion ChromatographyTable 4. Typical Accuracy Experiment Data for Area Response Factor.Deposited Expected Average Calculated %Concentration Concentration Area Concentration Recovered (ppm) (ppm) (µS/cms) (ppm)108 5.40 19.407 4.53 84.0135 6.75 26.918 6.20 92.0162 8.10 33.337 7.63 94.3Table 5. Typical Accuracy Experiment Data for Height Response Factor.Deposited Expected Average Calculated %Concentration Concentration Height Concentration Recovered (ppm) (ppm) (µS/cm) (ppm)108 5.40 1.30 4.59 85.0135 6.75 1.82 6.28 93.0162 8.10 2.25 6.82 94.8standard error of the intercept, and the slope of the linear regression curve from the Linearity deter-mination. Multiplying the S/N Estimate by 3.3 and 10 affords the estimate of the DL and QL, respec-tively. This calculation yielded an average DL of 0.23 ppm, and an average QL of 0.70 ppm, both of them by area response factor. These calculations were based on the amount of phosphate present in CIP-200. In order to correlate this number to the amount of CIP-200 present, the amount of phos-phate contained in a sample of CIP-200 must be determined. Then, taking into consideration the calculated content of phosphate in CIP-200, the DL for CIP would be around 0.11 nL and the quan-titation limit for CIP-200 would be around 0.32 nL of the detergent.Determination of phosphatein CIP-200 detergent/accuracyexperiments A set of recovery experiments were performed to assess the accuracy and precision of the method using CIP-200 samples. A concentration range going from 1.41 ppm to 16.9 ppm of phosphate was used as the calibration curve. This estimated recovery was obtained by dividing the response factor of each concentration recovered and divided by the slope of the linear regression curve of the found versus theoretical concentration for the phosphate. The CIP-200 samples were extracted form the cotton swab using mobile phase as the extracting solvent. 100 µL of diluted CIP-200 deposited on the stainless steel plates was diluted further in 2.00 mL of mobile phase and after that 20 µL of that was injected into the ion chromato-graphic system. The average % recovery of the CIP-200 samples was calculated to be 90.1% for the area response factor, and 90.9 % for the height response factor. Table 4 and Table 5 presents the data obtained from a typical accuracy experiment of CIP-100 from the stainless steel plates for area response factor and the height response factor, respectively. Figure 4 shows a typical chromato-gram of the ion chromatography analysis of phos-phate contained in a CIP-200 detergent sample.Conclusions Anion Exchange chromatography proved to be an excellent analytical technique for the determination of CIP-200 traces. The developed anion exchange chromatographic method has been evaluated over the linearity, precision, accuracy, and selectivity and proved to be convenient and effective for the quality control of cleaning validation samples. The method is fast and reliable affording turn around times convenient for the quality control laboratory. Solvents are mostly aqueous and its consumption is low which makes the method environmentally friendly. The DL and QL of the method are less than 1 ppm of phosphate in theZayas et alCIP-200 sample which translates to less than 1 nL of CIP-200, making it an excellent method for the determination of traces of CIP-200 in cleaning validation.AcknowledgementsJoan Roque gratefully acknowledges NIH, grant number 5R25 GM59429-08 for ﬁ nancial support.ReferencesAmerican Society for Testing and Materials (ASTM), Philadelphia, P.A.Annual Book of ASTM Standards (1984). 21 CFR 211.67, EquipmentCleaning and Maintenance. 21 CFR 211.160 (b), Laboratory Controls.Food and Drug Administration (FDA) Guidance Document for Industry “Analytical Procedures and Methods V alidation”, August 2000. Guideto Inspections of Cleaning Validation, FDA, 1993. ICH Harmonized Tripartite Guideline Validation of analytical procedures methodol-ogy Q2B. November 1996.Jackson, P.E. and Pohl, C.A. 1997. Advances in stationary phase develop-ment in suppressed ion chromatography. Trends Anal. Chem.,16:393–400.Lucy, C.A. 1996. Recent advances in ion chromatography: A perspective.J. Chromatogr. A,739:3–13.Roig-Navarro, A.F., Martinez-Bravo, Y. and López, F.J. et al. 2001. Simul-taneous determination of arsenic species and chromium(VI) by high-performance liquid chromatography–inductively coupled plasma-mass spectrometry. J. Chromatogr. A, 912:319–327. Sarzanini, C. 2002. Recent developments in ion chromatography. J.Chromatogr. A, 956:3–13.Small, H., Stevens, T.S. and Bauman, W.C. 1975. Novel ion exchange chromatographic method using conductimetric detection. Anal.Chem., 47:1801–1809.The United States Pharmacopoeia, USP 27, 2004 Chapter <1225>, Valida-tion of Compendial Methods.Vanatta, L.E. and Coleman, D.E. 2001. Ion-chromatographic analysis of common anions, acetate, and formate in 30% hydrogen peroxide Statistical evaluation of two automated microbore systems. J. Chro-matogr. A, 920:143–153.Zayas, J., Colón, H. and Garced, O. et al. 2006. Cleaning validation 1: Development and validation of a chromatographic method for the detection of traces of LpHse detergent. J. Pharm. Biomed. Anal.41:589–593.。

GLP要素解读

的质量保证计划清单及评估QA工作量。
GLP要素解读
COMPREHENSION OF GLP FACTORS
QA、SD、FM关系： • FM：负责提供资源（设施、人员、程序等）
考虑整体机构的运转与效益 • SD：负责试验的科学性和质量
考虑时限、费用、委托方…… • QA：独立于试验之外，负责试验按照GLP准则实施
2、ISO/IEC17025与CMA ISO/IEC 17025：25个要素；CNAS；认可，面向第一、二、三方；依据为国标；8707家 CMA：19个要素，特殊19条；两级认证，面向第三方；《计量法》的规定；约33000家
3、CNCA与CNAS CNCA：中国国家认证认可监督管理委员会；CNCA-GLP、国家级CMA CNAS：中国合格评定国家认可委员会；加入ILAC，故资质又称为CNAS
质量体系相关概念介绍
4、ISO/IEC17025与GLP 有相互借鉴的趋势；但各有各的适用领域 ······
人、机、料、法、环。
二、解读
1、人：资历符合的人员； 2、机：仪器，内部验证及外检； 3、料：物料，包括试剂、器皿等等耗材，须由合格供应商提供； 4、法：法规、体系文件（GLP的SOP，17025/CMA的四层体系文件）； 5、环：环境设施满足测试/培养需求。
质量保证程序仪器、材料和试剂供试品和参比物试验实施记录和材料的保存
GLP要素解读
COMPREHENSION OF GLP FACTORS
1.组织机构和人员 1）实验室应提清晰合理的组织架构；确保试验机构有足够的合格人员，人力资源和相应的支持服务来保证所进行的各类试验；建立人员培训和健康监督政策等。机构负责人对机构作为一个在GLP准则下运作的整体负有最终责任。项目负责人职责：项目负责人是试验项目管理的核心（single point），对试验的科学性和 GLP依从性负最终责任。 QAU职责：作为第三方，保证GLP得到遵从，为机构内GLP体系的有效性提供证据。档案员职责：对归档的材料负责；对从档案室借出的材料负责。试验人员职责：了解所承担计划书的内容及相关SOPs，掌握所承担试验部分的GLP准则；在GLP准则框架下，按照计划书及相关SOPs要求进行试验。

计算机专业英语词汇扩展

[编辑本段]AA ctive-ma ctive-mat t rix 阵主动矩阵Ad apte r card s 卡适配卡Ad van ced ced applica applica application tion 用高级应用An alytical alytical gra gra ph 表分析图表An alyze 析分析Animation Animations s 画动画Ap plication soft wa re 应用软件A rithme tic tic ope ope ra tion s 算算术运算Au dio-ou tput tput d d evice 音频输备出设备A cce ss ss time time 间存取时间a cce ss 取存取a ccu ra cy 性准确性ad net wo rk coo kie s 件广告网络信息记录软件Ad d-on s 件插件Ad dre ss 地址Ag ent s 理代理An alog signal s 模拟信号Ap plet plets s 序程序A synch ronou s communication communications s s po po rt 口异步通信端口A tta chment 件附件[编辑本段]BBa r code 码条形码Ba r code read er 条形码读器卡器Ba sic sic a a pplication 序基础程序Bina ry ry co co ding scheme s 二进制译码方案Bina ry system 统二进制系统Bit 特比特B ro wser 浏览器Bu s s line line 线总线Ba ckup ckup tape tape ca rt ridge ridge uni uni t s 元备份磁带盒单元Ba ndwid th 宽带宽Blue tooth 牙蓝牙B roa dband 带宽带Bu sine ss-to -bu sine ss 务企业对企业电子商务Bu sine ss-to -con sumer 企业对消费者Bu s 线总线[编辑本段] C Cable s 线连线Cell 箱单元箱Chain Chain p p rinte r 机链式打印机Cha ra cte r and re cognition cognition de de vice 字符标识识备别设备Cha rt 表图表Cha ssi s 架支架Chip 片芯片Cla rity 度清晰度Clo sed a rchite ctu re 封闭式体系结构Column 列Combination key 键结合键compute r competen competency cy 计算机力能力conne ctivit ctivity y 点连接，结点Continuo Continuou u s-speech re cognition system 连续语言识别统系统Cont rol rol unit unit 操纵单元Co rdle ss ss o o r wirele ss ss mo mo u s e 标无线鼠标Cable Cable modem modem s 有线器调制解调器ca rpal rpal tunnel tunnel synd rome 腕骨神经症综合症CD-ROM 盘可记录光盘CD-RW 盘可重写光盘CD-R 可记录压缩光盘Channel 道信道Chat group 组谈话群组chlorofluo chlorofluoroca roca rb on s(CFCs) s(CFCs) ]]烷氯氟甲烷Client 端客户端Coa xial xial cable cable 缆同轴电缆cold site 站冷网站Comme rce se rvers 器商业服务器Communica Communication tion tion chan chan nel 道信道Communica Communication tion system s 统信息系统Compa ct ct di di sc re writable Compa ct ct di di sc 盘光盘compute r abu se se amendme amendme amendment nt s act of of 1994119941994案计算机滥用法案compute r crime 罪计算机犯罪compute r e thics 计算德机道德compute r f ra ud ud and and and abu abu se se a a ct o f f 19861986案计算机欺诈和滥用法案compute r mat matching ching ching and and pri vacy vacy p p rote ction ction a a ct ct o o f f 19881988计算机查找和隐案私保护法案Compute r net wo rk 络计算机网络compute r suppo rt spe ciali s t 家计算机支持专家compute r t echni cian 员计算机技术人员compute r t raine r 师计算机教师Conne ction ction de de vice 备连接设备Conne ctivi ty 接连接Con sume r-to -con sume r 人个人对个人coo kie s-cu tte r p rog ram s 信息记序录截取程序coo kie s 序信息记录程序cracker 手解密高手cumulative t rauma rauma didi s o rde r 积累性损伤错乱 Cyberca Cybercash sh 金电子现金Cyberspa Cyberspace ce 间计算机空间cynic 愤者世嫉俗者[编辑本段]DData ba s e 库数据库da taba se se file file files s 件数据库文件Data ba se mana ger 数据理库管理Data bu s 线数据总线Data projecto projector r 机数码放映机De skto p system system unit unit 元台式电脑系统单元De stination stination file file 件目标文件Digital Digital came came ra s 机数码照相机Digital Digital noteb noteb oo ks 本数字笔记本Digital Digital bideo bideo camera 数码机摄影机Di screte -speech re cognition system 不连续语言识统别系统Do cument 档文档do cument file s 件文档文件Dot -mat ri x x p p rinte r 机点矩阵式打印机Dual -scan -scan monito monito monitor r 器双向扫描显示器Dumb Dumb te te rminal 端非智能终端da ta s e cu rity 数据全安全Data t ran smi ssion specifi cation s 数明据传输说明da taba se se admini admini s t rat or 数据库管员理员Data play 器数字播放器Demodulation 调解调denial denial o o f s e rvice rvice a a ttack 击拒绝服务攻击Dial-u p s e rvice 务拨号服务Digital Digital ca ca sh 金数字现金Digital signal s 数号字信号Digital sub scribe r line 路数字用户线路Digital Digital ve ve rsatile rsatile di di sc 盘数字化通用磁盘Digital Digital video video di s c 数字化视频盘光盘Di rect acce ss 取直接存取Di rect ory sea rch 索目录搜索di sa s t er er re re co ve ry plan 灾难恢复计划Di sk sk ca ca ching 存磁盘驱动器高速缓存Di skette 磁盘Di sk 碟磁碟Di stribu ted ted dat dat a a p p roce ssing system 分部数据处理统系统Di stribu ted ted p p roce ssi ng 理分布处理Domain Domain code code 码域代码Do wnloading 载下载DV D 数字化通用磁盘DV D-R 可写DV D DV D-RAM D-RAM DVD DVD 随机存取器DV D-ROM 只读DVD [编辑本段]Ee -boo k 器电子阅读器E xpan s i on on ca ca rd s 卡扩展卡end u s e r 户终端用户e -ca s h 金电子现金e -commerce 务电子商务ele ct ronic ca s h 电金子现金ele ct ronic comme rce 务电子商务ele ct ronic communica communication tion s p rivacy rivacy act act act of1986of1986电子通案信隐私法案 en cryp ting 术加密术ene rg y sta r 星能源之星En te rp ri se computing 化企业计算化en vironment 境环境E ra sable sable opti opti cal cal di di sks 盘可擦除式光盘e rgonomi c s 学人类工程学e thics 道德规范E xte rnal rnal modemmodem 外置调制解调器 e xt ranet 企业网外部网[编辑本段]FFax Fax ma ma chine 机传真机Field 域Find 索搜索FireWi re po rt 火口线端口Firm wa re 件固件Fla sh RAM 存闪存Flatbed sca nner 台器式扫描器Flat -panel -panel monito monito monitor r 器纯平显示器flop py py di di sk 盘软盘Fo rmatting toolbar 条格式化工具条Fo rmula 式公式Fun ction 数函数f air credit repo rting rting a a ct o f f 19701970公平信用报告法案Fibe r-optic cable 缆光纤电缆File File comp comp re ssion 缩文件压缩File File decomp decomp re ssion 缩文件解压缩filte filter r 滤过滤fi re wall 墙防火墙fi re wall 墙防火墙Fixed Fixed di di sk 盘固定硬盘Fla sh memo ry 存闪存Flexible Flexible di di sk 盘可折叠磁盘Floppie Floppies s 盘磁盘Floppy-di sk ca rt ridge 盒磁盘盒Fo rmatting 化格式化f re edom edom of of of info info rma tion tion act act act of of of 19701970信息自案由法案f re quency 率频率f ru st ra ted 折受挫折Full-du Full-duplex plex communication 信全双通通信[编辑本段]GG ene ral-p urp o se ap plication 序通用运用程序Giga hertz 赫千兆赫G ra phic phic tablet tablet 绘板图板g reen pc 机绿色个人计算机G ro p p by by 排序 [编辑本段]Hhan dheld dheld compu compu ter 手脑提电脑Ha rd copy 贝硬拷贝ha rd rd di di sk 盘硬盘ha rd wa re 件硬件Help 助帮助Ho st st compute compute computer r 机主机Home Home page page 页主页Hyperlin Hyperlink k 超接链接ha cker 客黑客Half -duple x x communi communi cation 信半双通通信Ha rd -di sk sk ca ca rt ridge 盒硬盘盒Ha rd -di sk sk pa pa c k 组硬盘组Head cra s h 磁头碰撞hea der 题标题help help de de sk spe ciali s t 家帮助办公专家helpe helper r ap plication plications s 帮助软件Hie ra rchi cal cal net net wo rk 络层次型网络hi sto ry file 件历史文件hit hits s 录匹配记录ho rizontal rizontal po po rtal 户横向用户ho t site 站热网站Hybrid Hybrid n n et wo rk 络混合网络[编辑本段]IIma ge ge cap cap tu ring ring devi devi ce 备图像获取设备info rma tion tion te te chnology 术信息技术I n k-jet k-jet p p rinte r 墨水喷射印刷机I nteg rate d d package package 件综合性组件I ntelligent ntelligent te te rminal 备智能终端设备I nte rg rated ci rcuit 路集成电路I nte rfa ce ce card card cards s 卡接口卡I nte rnal rnal modem modem 器内部调制解调器inte rne t t telepho telepho telephony ny 话网络电话inte rne t t te te rminal 端互联网终端I dentification 别识别i -d rive 器网络硬盘驱动器illu illusion sion sion of of anonymit anonymity y 想匿名幻想inde x s e arch 索索引搜索info rma tion tion pu pu she rs 器信息推送器initializing 化初始化in stant stant me me ssa ging 息计时信息inte rnal rnal ha ha rd di sk 内置硬盘I nte rnet hard hard d d rive 网络硬盘驱动器int intrane rane t 网企业内部网[编辑本段]Jjo ysti c k 杆操纵杆[编辑本段]Kkeywo rd sea rch 关键字搜索[编辑本段]Lla ser ser p p rinter 激机光打印机La yout file files s 件版式文件Ligh t t pen pen 笔光笔Lo cate 位定位Logi cal cal ope ope ration s 算逻辑运算Lan d s 面凸面Line Line o o f sigh t t communication communication 信视影通信Lo w w ban ban dwidth 低带宽lu rking 伏潜伏[编辑本段]MMain Main boa boa rd 板主板Ma rk sen sing 测标志检测Me chanical chanical mou mou se 标机械鼠标Memo ry 存内存Menu 单菜单Menu Menu b b ar 条菜单条Microp Micropro ro ce sso r 器微处理器Micro Microsecond second seconds s 秒微秒Modem ca rd 器调制解调器Monito Monitor r 器显示器Mot Motherboa herboa herboard rd 板主板Mou se 标鼠标Multifun Multifunctional ctional ctional de de vice 备多功能设备Magne Magnetic tic tic ta ta pe reel s 卷磁带卷Magne Magnetic tic tic ta ta pe streamers 条磁带条mailing mailing li li s t 表邮件列表Medium Medium band band 媒质带宽met meta a sea rch rch engine engine 擎整合搜索引擎Micro Microwa wa ve 波微波Modem 器解调器Modulation 调解调[编辑本段]NNet PC 网络计算机Net wo rk rk adapte adapte adapter r ca rd 卡网卡Net wo rk rk pe pe rson al al compute compute r 网络个人电脑Net wo rk rk te te rminal 端网络终端Note boo k compute r 脑笔记本电脑Note boo k system system unit unit 笔记元本系统单元Nume ric ric en en t ry 入数字输入na tional tional info info rmation rmation inf inf infra ra st ructu re re p p rote ction ction a a ct ct o o f1996案国际信息保护法案 na tional s e rvice rvice p p ro vider 全国性服商务供应商Net wo rk rk a a rchite ctu re 网络体系结构Net wo rk rk b b ridge 桥网桥Net wo rk rk gate gate way 网关ne twork twork manage manage manager r 员网络管理员ne wsg roup 组新闻组no elect electroni roni c c thef thef t t act act act of19of1997法无电子盗窃法Node 点节点Non volatile s t ora ge 储非易失性存储[编辑本段]OO bject bject embe embe dding 入对象嵌入O bject bject lin lin king 目标链接O pen pen a a rchit ect ure 开放式构体系结构O pe ration ration S S ystem 统操作系统O ptical ptical di di sk 盘光盘O ptical ptical mou mou se 标光电鼠标O ptical scann er 光电扫描仪O utline 纲大纲o ff -line -line browsebrowse browsers rs 离线浏览器 O nline sto rage 联机存储[编辑本段]Ppalmtop compu ter 掌上电脑Pa rallel rallel po po rt s 口并行端口Pa ssi ve -mat rix 阵被动矩阵P C ca rd 卡个人计算机卡Pe rsonal rsonal la la s e r p rin ter 个人激机光打印机Pe rsonal video video reco reco rde r ca rd 卡个人视频记录卡Ph oto oto p p rinte r 机照片打印机Pi xel 素像素Pla tfo rm scanne r 仪平版式扫描仪Plo tte r 仪绘图仪Plug Plug a a nd nd play play 用即插即用Plug -in -in boa boa rd s 卡插件卡Poin ter 指示器Poin ting sti c k 棍指示棍Po rt 端口Po rtable scanne r 仪便携式扫描仪P re senta tion tion file file s 稿演示文稿P re senta tion tion g g raphics 序电子文稿程序P rima ry sto rage 存主存P ro cedu re s 规程P ro ce sso r 机处理机P rog ramming cont control rol rol lanugage lanugage 程序控制言语言 Pa cket ckets s 数据包Pa rallel rallel data data t ran smi ssion 输平行数据传输Pe er-to -pee r net netwo wo rk system 统点对点网络系统 pe rson -pe rso n n auction auction site 个人对个点人拍卖站点 ph ysi cal s e cu rity 全物理安全Pit Pits s 面凹面plug -in 序插件程序Polling 询轮询p riva cy 隐私权p roa ctive 主动地p rog ramme r 员程序员P ro tocol s 协议p ro vider 供应商p ro xy se rve r 务代理服务pull pull p p rodu ct s 推取序程序pu sh sh p p rodu ct s 序推送程序[编辑本段]RRAM cache 随机高速器缓冲器Range 围范围Re cord 记录Relational Relational da da taba s e 关系数库据库Replace 替换Re solution 率分辨率Ro w 行Read -only 只读Refo rma tting 组重组regional se rvice rvice p p rovide r 商区域性服务供应商 repe titive titive motion motion motion inju inju ry 反复伤性动作损伤re ve rse di re cto ry 反向目录right to to finan finan financial cial cial pri pri vacy vacy a a ct ct of of of 11979案财产隐私法案 Ring Ring net net wo rk 网环形网[编辑本段]SS canne r 器扫描器Se arch 找查找Se conda ry sto rage rage de de vice 备辅助存储设备Semi condu cto r 体半导体Se rial rial po po rt s 口串行端口Se rve r 器服务器Sh ared ared la la s e r p rinte r 共享激光打印机Sh eet 格表格Silicon chip 片硅片Slo t s 槽插槽Sma rt ca rd 卡智能卡So ft copy 贝软拷贝So ft wa re suite 议软件协议So rting 序排序So urce urce file file 件源文件Sp ecial -pu rpo s e application 件专用文件Sp re ad shee t 表电子数据表S tanda rd rd toto olbar 标准工具栏 Su pe rcompu ter 巨型机S ystem ystem ca ca bine 箱系统箱S ystem ystem clo clo c k 钟时钟S ystem s o ft wa re 件系统软件Sa tellite/ai tellite/air r conn ection se rvi ce s 卫星无线务连接服务sea rch engine engines s 擎搜索引擎sea rch provide providersrs 搜索供应者 sea rch se rvi ce s 器搜索服务器Se cto rs 区扇区secu rit y 全安全Se nding nding and and re ceiving ceiving de de vice s 发备送接收设备Se quential quential acce acce ss 取顺序存取Se rial rial da da ta ta t t ran smi ssion 信单向通信s i gnatu re line 档签名档snoop wa re 件监控软件soft wa re cop yrigh t t act act act of1980of1980软件案版权法案soft wa re pi ra cy 版软件盗版Solid Solid-state -state sto rage 固态存器储器specialize specialized d sea rch rch engine engine 擎专用搜索引擎spide rs 虫网页爬虫spi k e 压尖峰电压S ta r net netwo wo rk 星型网S t rategy 案方案subject 主题sub scription scription add add re ss 址预定地址Su pe rdi sk 超级磁盘su rfing 浪网上冲浪su rge rge p p rote cto r 器浪涌保护器system s s analyst analyst 师系统分析师[编辑本段]TTable 表二维表Telephony 学电话学Televi sio n n boaboa rd s 电视扩展卡 Te rminal 端终端Template 板模板Text ent ry 入文本输入The rmal rmal p p rinte r 刷热印刷Thin Thin client client 客瘦客Toggle key 键触发键Toolba r 栏工具栏Tou ch screen 屏触摸屏T rackball 球追踪球TV TV tu tu ne r ca rd 卡电视调谐卡T wo -sta te system 统双状态系统t echni cal cal write write r 者技术协作者t echno st re ss 术重压技术t elnet 录远程登录Time-sha Time-sharing ring system 统分时系统Topology 拓扑构结构T racks 道磁道t ra ditional ditional coo coo k i e s 程传统的信息记录程序序T wi sted pair 绞双绞[编辑本段]UUnicode 统一准字符标准uploading 传上传u senet 世界性新络闻组网络[编辑本段]VVi rtual rtual memo memo ry 虚存拟内存Video di splay scre en 屏视频显示屏Voi ce recognition system 统声音识别系统ve rtical rtical po po rtal 户纵向门户video video p p riva cy cy p p ro tection tection act act act of of of 19881988视频案隐私权保护法案viru s checke r 序病毒检测程序viru s 毒病毒Voi ceband 宽音频带宽Vola tile sto rage 易失性存储voltage su rge 涌电涌[编辑本段]WWand re ade r 入条形码读入Web 网络Web a ppliance 环球网设备Web p age 页网页Web site site addadd re ss 网络地址 Web te rminal 端环球网终端Web cam 头摄像头Wha t-i f f analysi analysi s 析假定分析Wi rele ss revolu tion 命无线革命Wo rd 长字长Wo rd rd p p ro ce ssing 理文字处理Wo rd wrap 行自动换行Wo rkshee t t file file 件工作文件web web au au ction s 卖网上拍卖web web b b road ca ste rs 网络广播web web po po rtal s 站门户网站web s i te s 站网站web sto ref ron t t crea crea tion tion package package packages s 包网上商店创建包web sto ref ron t s 店网上商店web web u u tilities 网上序应用程序web -do wnloading wnloading utilitie utilitie utilities s 网页下序载应用程序webma ste r web 员站点管理员web 网万维网Wi rele ss ss modem modem s 无线调制器解调器wi rele ss s e rvice rvice p p ro vider 无线商服务供应商wo rld wide wide web web 万维网wo rm 毒蠕虫病毒Write -p rote ct notch 写保口护口[编辑本段]其他缩写DV D digital digital be be rsatile 盘数字化通用光盘IT IT info info rma tion tion te te chnology 术信息技术CD CD compa compa ct ct di di sc 压缩盘P DA p ersonal ersonal digital digital digital a a ssi stant 个人数字助理RAM random random a a cce ss ss memory memory 器随机存储器WWW Wo rld Wide Web 万维网DBMS DBMS da da taba se se management management syst em 统数据库管理系统HTML HTML Hype Hype rte xt xt Ma Ma rkup rkup Langua Langua ge 言超文本标示语言O LE LE object 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Identification of genomic signatures for the design of assays for the detection and monitor

IDENTIFICATION OF GENOMIC SIGNATURES FOR THE DESIGN OF ASSAYS FOR THE DETECTION AND MONITORING OF ANTHRAX THREATSSORIN DRAGHICI1,†,PURVESH KHATRI1,2,†,YANHONG LIU4,KITTY J CHASE3,ELIZABETH A BODE3,DAVID A KULESH3,LEONARD P WASIELOSKI3,DAVID A NORWOOD3,JAQUES REIFMAN2 1Dept.of Computer Science,Wayne State University,Detroit,MI482022Bioinformatics Cell,Telemedicine and Advanced Technology Research Center, US Army Medical Research and Materiel Command,Ft.Detrick,MD217013Diagnostic Systems Division,US Army Medical Research Institute ofInfectitious Diseases,Ft.Detrick,MD217014US Dept.of Agriculture,Agricultural Research Service,Eastern RegionalResearch Center,Wyndmoor,PA19038Sequences that are present in a given species or strain while absent from or diﬀerent in any other organisms can be used to distinguish the target organism from other related or un-related species.Such DNA signatures are particularly important for the identiﬁcation of genetic source of drug resistance of a strain or for the detection of organisms that can be used as biological agents in warfare or terrorism.Most approaches used toﬁnd DNA signatures are laboratory based,require a great deal of eﬀort and can only distinguish between two organisms at a time.We propose a more eﬃcient and cost-eﬀective bioinformatics approach that allows identiﬁcation of genomicﬁngerprints for a target organism.We validated our approach using a custom microarray,using sequences identiﬁed as DNAﬁngerprints of Bacillus anthracis.Hybridization results showed that the sequences found using our algorithm were truly unique to B.anthracis and were able to distinguish B.anthracis from its close relatives B.cereus and B.thuringiensis.1.IntroductionThe area of organism identiﬁcation using DNA sequences has many appli-cations in various life science areas.However,there are also many chal-lenges.For instance,sheep pox and goat pox viruses are so closely related that they cannot be distinguished using clinical signs,pathogenesis or sero-reactivity.30Furthermore,both cross-infectivity and cross-resistance have†These authors should be considered jointﬁrst authors.been reported38to the point that the two were thought to be caused by a single viral species.However,genetic analysis demonstrated that sheep pox and goat pox are actually caused by two related,but genetically dis-tinct viruses.Furthermore,the identiﬁcation of a few base pair diﬀerences in the sequence coding for the P32protein allowed the design of a poly-merase chain reaction(PCR)restriction fragment length polymorphism (PCR RFLP)assay able to distinguish between the two species.This assay involves a PCR ampliﬁcation with a common primer,followed by a diges-tion with a Hinf I restriction enzyme that produces fragments of diﬀerent sizes allowing the identiﬁcation of the two species.The issue of distinguishing between diﬀerent species is somewhat aca-demic if the two species exhibit both cross-infectivity and,most impor-tantly,allow passive cross-protection as the sheep pox and goat pox do.37 However,this is not always the case.Genes that are present in certain isolates of a given bacterial species and are substantially diﬀerent or absent from others can determine important strain-speciﬁc traits such as drug re-sistance13and virulence.51As an example,B.anthracis,B.cereus,and B. thuringiensis are genetically so close that it has been proposed to consider them a single species.27At the same time,these bacteria are very diﬀerent on a phenotypic level.B.cereus is a frequent food contaminant but only a mild opportunistic human pathogen;16,28B.thuringiensis is actually a use-ful bacterium being used as a pesticide46while B.anthracis is a virulent pathogen for mammals that has been used as a bio-terror and biological warfare agent.12,53In such cases,the identiﬁcation of an organism-speciﬁc DNA sequence gains an increased importance.Even if such sequences are not functionally active,they can still be extremely useful if used as geneticﬁngerprints. DNA sequences that are present in a given species while absent from any other organisms can be used to distinguish the target organism from other related or un-related species.If such geneticﬁngerprints were available for organisms that can be potentially used as biological or terrorist weapons, the task of rapid threat identiﬁcation,characterization,and selection of ap-propriate medical countermeasures could be immensely facilitated.Genetic ﬁngerprints can also aid identiﬁcation of genetic source of drug resistance of a strain,17which can be useful to drug developers in pharmacogenomics.2.Existing workThe existing work in the areas of organism identiﬁcation using DNA sig-natures can be divided into two diﬀerent categories.One approach uses a laboratory assay to identify the organism.Techniques used include ampli-ﬁed fragment length polymorphism(AFLP),44,45suppression subtractive hybridization(SSH)3and custom DNA microarrays.36A second approach uses a purely bioinformatics analysis of the characteristics of the genomes of various species and extracts those features that are characteristic to in-dividual species.The laboratory based approach does not necessarily require information about the entire genomes involved and is better suited for the development of assays for monitoring and identiﬁcation of biological threats.For in-stance,SSH,a PCR-based DNA subtraction method,allows identiﬁcation of genomic sequence diﬀerences in a“tester”DNA relative to a“driver”DNA.AFLP relies on the analysis of aﬂuorescence based signal propor-tional to the size of various DNA fragments.49SSH and AFLP have been successfully used to identify genomic sequence diﬀerences between various strains or species of bacteria.4,5,10,31,44The major drawback of this ap-proach is that it permits identiﬁcation of genomic diﬀerences only between two organisms.For instance,in order to diﬀerentiate two species,one needs to use an SSH assay to compare each strain of one species with each strain of the other species.44Clearly,this approach cannot be used to provide a genomic signature that would diﬀerentiate a given organism from all others.The in silico approach to identifying genomic signatures is usually based on an analysis of the entire genomes involved and aims at extracting fea-tures such as species-speciﬁc codon usage.1,2,23,32–34,52While this type of genomic signature can be informative about the given organisms and the relationships among them,it may not be directly usable for detection and monitoring purposes.Comparative sequence analysis has also been useful in detecting in-tronic and intergenic regions25,40as well as uncovering novel repeated structures.18,26Several genome scale alignment tools are available:MUM-mer,14,15,39AVID,11MGA,29WABA,35and GLASS7among others.Tax-Plot22provides visual representation of protein homologs in microbial and eukaryotic genomes.Most of these pair-wise a alignment tools assume that the input genomes are closely related.Therefore,there will be a mapping a MGA is a multiple alignment tool but the alignment is still computed pair-wise.of large subsequences between the two input genomes.In turn,they assume that these large subsequences,appearing in the same order in the closely related genomes,are very likely to be part of theﬁnal alignment.These regions are used as anchors for the alignment of the input genomes.In general,anchor-based genome alignment programsﬁrst create a suﬃx tree from the two input genomes.A suﬃx tree is a compact representation of all suﬃxes in the input string.41,54A suﬃx of a string is a substring starting at any position in the string and extending up to the end of the string.Next,the suﬃx tree is searched for sequences that appear in both input genomes.These exact matching subsequences are known as maxi-mal exact matches(MEMs).The anchors are chosen from these MEMs. Diﬀerent programs apply diﬀerent criteria for the selection of anchors.For instance,MUMmer uses the longest increasing subsequence(LIS)24for the selection of anchors.14MUMmer allows the selection of overlapping an-chors whereas AVID and MGA only select non-overlapping anchors.Since MGA allows alignment of more than two genomes,it only selects MEMs that are present in all of the input genomes.AVIDﬁrstﬁnds the length of the longest MEM and discards all the MEMs that are less than half the length of the longest MEM.After selecting the anchors,MUMmer employs a variant of the Smith-Waterman algorithm47to close the gaps between the anchors.MGA and AVID close the gaps by recursively creating suﬃx trees for the non-anchored parts of the input genomes and hence,gradu-ally reducing the gap sizes.Once the gaps are smaller than a threshold, MGA and AVID close them using the ClustalW48and Needleman-Wunsch algorithms,42respectively.These large number of tools are all geared towardsﬁnding large-scale similarities between two or more genomes.Our focus here is diﬀerent. While these algorithms were developed toﬁnd sequence similarities,our goal is toﬁnd sequence dissimilarities.These two problems are related but not reciprocal.Simply put,one cannot just take the complement of the sequences found in a similarity search and use them as genomic signatures. The main reason is related to the fact that a search aiming toﬁnd similarity will sometimes discard entire blocks after only a summary inspection be-cause they are not suﬃciently similar to the target sequence.On the other hand,a search aiming toﬁnd dissimilarities,i.e.,unique signatures,has to actually focus on exactly those areas that are discarded without extensive analysis during the similarity search.Here,we propose an algorithm forﬁnding genomicﬁngerprints that distinguish an organism from all other organisms with known genomes.As the number of sequenced organisms increases,this approach has the potential to substitute existing laboratory based approaches such as AFLP and SSH.In this paper,we used this approach toﬁnd a genetic signature for B.anthracis.Identiﬁcation of genomic regions unique to B.anthracis can provide clues to its genetic relationship to other highly similar organisms. Related work for the detection of B.anthracis used plasmid-encoded toxin genes for rapid DNA-based assays.8However,these failed to detect non-plasmid containing strains of B.anthracis isolated from the environment.50 Also,there have been eﬀorts to design real-time PCR assays.However, these assays only targeted a single locus and they yielded false-positive results with some strains of B.cereus.20,433.Analysis methodsOur goal is toﬁnd unique DNA sub-sequences for a given target genome across all available known genomes.An obvious approach is to compare (i.e.,align)the genome of our interest against all available known genomes. These alignments will reveal the parts of the target genome that do not align with any other genome(i.e.,are unique to the target genome).However, this seemingly simple approach is computationally very expensive.The GenBank database at NCBI contains nucleotide sequences from more than 140,000organisms.9The length of these genomes vary from a few thousand base pairs to a few billion base pairs.Aligning the input genome with each of these genomes is computationally unfeasible.The amount of computation can be considerably reduced by using the phylogenetic background of the target.Today biologists agree that various organisms have evolved from common ancestors.During evolution,func-tional genomic elements are conserved.Hence,two closely related genomes are expected to have many matching subsequences.If a subsequence that distinguishes the target from all organisms exists,this subsequence will also distinguish the target from its closest relative.Hence,a good initial set of potential genomic signatures can be obtained by comparing the target only with its closest relative and by retaining only those sequences that are dif-ferent.Subsequently,each of these potential signatures is compared with all other known genomes.This approach drastically reduces both the number of comparisons required as well as the length of sequences to be compared (from a few million to a few thousand base pairs,at most).In order toﬁnd the exact matching sequences between the target and itsclosest relative,we start by using their concatenated sequences to create a suﬃx tree.We then use a suﬃx tree search algorithm as the one employed in MUMmer toﬁnd the exact matching sequences in both genomes.Since our goal is to determine a set of relatively short sequences to be used on a microarray type assay,we have to search both the forward and the reverse strands.Any sequences that match between the two organisms are removed from further consideration.The result is a set of short segments of the target genome that can be considered potential signatures.These are then compared with all sequences in the blast-nt21database from NCBI.6We consider a sequence is unique for the target genome if it does not align to any sequence from any other organism with an expected value(E-value) less than a threshold of0.01.Fig.1provides an overview of this approach.Figure1.The genomicﬁngerprinting approach.Two genomes are searched for matching subsequences(MEMs).The MEMs are removed from the target genome and the remaining segments of the target genome(A1,A2,...,A n)are searched against the nt database.If the length of a segment is less than the user speciﬁed length,it is discarded and not searched in the nt database.As shown,if a sequence does not align with any sequence from another organism with E value less than the speciﬁed threshold it is considered as a sequence unique to the target genome.4.Results and discussionIn order to validate our approach,we designed a custom microarray using sequences identiﬁed as genomicﬁngerprints for B.anthracis.This arraywas then hybridized with B.anthracis and B.cereus.In order toﬁnd a genomic signature for B.anthracis we proceeded as follows.We searched the B.anthracis str.Ames genome(GenBank contig accession number NC03997)for subsequences of30base pairs or more matching anywhere(direct and reverse strand)with sequences from the genome of B.cereus ATCC14579(GenBank contig accession number NC004722).We chose B.cereus ATCC14579genome as a closely re-lated genome because it is considered to be a good representative of the B.cereus family.19Then,we removed all of matching sequences from the B.anthracis genome.This step produced over6,000sequences of length 50or more.These sequences were then searched against the nt database using blastn.The sequences in the BLAST output that were not found in any other organism with E value less than0.01were retrieved and con-sidered part of the genomicﬁngerprints of B.anthracis.There were140 such sequences.Note that this analysis stage also removed sequences that matched the genomes of other close relatives of B.anthracis,such as B. thuringiensis,without ever directly comparing them.These140target se-quences were provided to CombiMatrix(Mukilteo,WA)for the design of a custom biMatrix designed2probes for80target sequences and1probe for22target sequences(for a total of182probes for102target sequences)with melting temperature in the range of70◦C to75◦C and a length of35base pairs or more.Probes of the required length and melting temperatures could not be identiﬁed for the remaining38target sequences. The microarray was designed with three replicates of each of the182probes.The custom microarray was then hybridized with samples of B.an-thracis and B.cereus.The hybridization results showed that18probes only hybridized to the B.anthracis sequences indicating that they were true genomicﬁngerprints of B.anthracis.Table1provides the positions of the sequences on B.anthracis genome that were found to be unique in the microarray experiment.Surprisingly,many of the initial182probes also hybridized with B. cereus.We further searched these cross-hybridizing probes against the blast-nt database.For the probes that hybridized to B.cereus the re-sults of this comparison showed that although the target sequences of those probes are only present in B.anthracis,the part of the target sequence on which the probes were designed was not unique to B.anthracis and is present in other genomes.This shows that the probe design stage lost some speciﬁcity due to its unique added requirements:melting temperatures in a very narrow range,limited lengths,etc.In all cases,although the initial,longer sequence was unique across the blast-nt database,by selecting a shorter subsequence,the probe became unspeciﬁc.Hence,another BLAST search is recommended before printing the assay,to check whether the sub-sequences selected as probes continue to be good signatures for the target organism.Table1.The following18probes identify17unique se-quences of B.anthracis(Ames).Theﬁrst and secondcolumns indicate the start and end,respectively,of the tar-get sequences from B.anthracis.The third and the fourthcolumn are the start and end positions,respectively,on thecorresponding target sequences for which probes were de-signed.Sequence start Sequence end Probe start Probe end175,231175,455644175,567175,6773671488,976489,620130166945,569946,5961511901,629,5221,630,5384895231,629,5221,630,5385295681,845,0011,845,3631111452,021,5352,022,9194915292,098,6192,099,2745916252,783,1902,783,40517542,918,7882,920,25197710133,037,8563,038,1131151523,524,6493,524,73117553,808,0693,809,0467978343,821,6173,822,1634494834,374,3644,375,4782273114,375,5814,376,1231491864,933,4054,933,4829435.ConclusionDNA sequences that are present in a given species or strain while absent from any other organism can be used to distinguish the target organism from other related or un-related species.The identiﬁcation of such DNA signatures is particularly important for organisms that may be potentially used as biological warfare agents or terrorism threats.Most approaches used to identify DNA signatures are laboratory based and require a signiﬁcant eﬀort and time.A bioinformatics approach can provide results faster and more eﬃciently.However,most tools built forgenome comparisons only allow alignment of two genomes at a ing this approach toﬁnd unique DNA signatures across all known organisms is unfeasible.In addition,all existing tools are limited toﬁnding the similarity between two genomes.In contrast,looking for DNA signatures requires the development of tools that identify sequence dissimilarities.In this paper,we describe an approach toﬁnd the DNAﬁngerprints of an organism.We used this approach toﬁnd a set of unique sequences for B.anthracis which were then used to design probes for a DNA microarray.The hybridization results revealed that a subset of these probes were truly unique to B.anthracis and were able to distinguish between B.anthracis and B.cereus,which is a close genetic relative.AcknowledgementsThis work was supported by the research area directorates of the US Army Medical Research and Materiel Command and the Defense Threat Reduc-tion Agency.Theﬁrst two authors are also supported by:NSF DBI-0234806,NIH1S10RR017857-01,MLSC MEDC-538and MEDC GR-352, NIH1R21CA10074001,1R21EB00990-01and1R01NS045207-01. 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西格玛管理(1)(1)

2020/8/6 Thursday
西格玛管理(1)(1)
What are your Expectations?
I would like to capture your expectations for the day?
Agenda
Introduction & overviewDemystifying Six SigmaCreating the Six Sigma CultureManaging the six sigma cultureTotal cycle Time ReductionSuccess Examples Around the worldHow to Implement Six Sigma in your businessQ & AClosing comments
1988 Malcolm baldrige nation quality award Mapped ISO 9001 into quality system review(QSR)
1992 10x redustion in defect eveery 2 years
customer satisfaction metrics 10x times
Key beliefs– how we will always act • Constant respect for people • Uncompromising integrityKEY GOALS– what we must accomplish • Best in class —People —Markting —Technology —Products:software\hardware and systems —Manufaction —Service • Increased global market share • Superior finacical resultsKEY INITATIVES– how we will do it • Six sigma quality • total cycle time reduction • product manufaction and environmental leadership • Prfit improvement •Empowerment for all in a participative Cooperative and creatice workplace

建筑施工专业英语词典IL

II (enthalpy) 焓I (inertia) 惯性I (inlet) 入口，进口I (inner) 内部的I (input) 输入I (intensity) 强度I (interrupt) 中断I (moment of inertia) 惯性矩，转动惯量IA (indirect address) 间接地址IA (initial appearance) 初始状态IAC (interim acceptance criteria) 临时验收准则IAC (iterative analog computer) 迭代模拟计算机IACS (International Annealed Copper Standard) 国际退火铜标准IAD (initiation area discriminator) 初始区域鉴别器IADIC (integrated analog-to-digital converter) 整体模拟-数字转换器IAEA (International Atomic Energy Agency) 国际原子能机构IAGC (instant automatic gain control) 瞬时自动增益控制I amplifier I [信道]放大器IAN (irregularly activated network) 不规则激励网络IAR (instruction address register) 指令地址寄存器I-bar 工字钢IBC (interbuilding coffin) 厂内屏蔽运输容器I-beam 工字梁，工字钢IBG (interblock gap) 组间间隔IBPA (integrated burnable poison absorber) 一体化可燃毒物吸收器IC (indicating controller) 指示控制器IC (information center) 信息中心IC (initial condition) 初始条件IC (input circuit) 输入电路IC (instruction counter) 指令计数器I&C (instrument and control) 仪表与控制，热控IC (integrated circuit) 集成电路IC (interchange center) 交换中心IC (intercooler) 中间冷却器IC (internal connection) 内部连接IC (ionization chamber) 电离室ICAD (integrated control and display) 整体控制和显示ICB (intercomputer buffer) 计算机间缓冲器ICC (integrated component circuit) 集成元件电路ICCDP (integrated circuit communication data processor) 集成电路通信数据处理器ICCS (in-core control structure) 堆内控制构件ice 冰ICE (input checking equipment) 输入检验设备ice age 冰期ice bank 冰块组ice bath 冰点槽，冰浴，冰槽iceberg 冰山icebox 冰箱icebox effect 冰箱效应ice-cap climate 冰盖气候ice condensating containment 冰冷凝式安全壳ice condenser 凝冰器，冰冷凝器ice condenser containment system 冰冷凝器安全壳系统ice condenser module 冰冷凝舱ice condenser reactor containment 冰冷凝器反应堆安全壳ice condenser system 冰冷凝器系统iced containment 置冰安全壳ice disposal 冰层处理ice floe 浮冰ice fog 冰雾ice load 覆冰负载，覆冰负荷ice melting current [导线]熔冰电流ice melting point 冰[熔]点ice point 冰点(计温学的基准点)ice trap 冰阱，冷阱ice unloading 脱冰ICF (inertial confinement fusion) 惯性约束聚变ICF (intercommunication flip-flop) 内部通信触发器ICG (internal conversion gain) 内转换增益I channel I信道icicle 毛刺icing 结冰ICL (incoming line) 引入线IC menu 初始工况菜单icon 图象；(电脑)图标，图示影像ICON (integrated control) 集中控制iconolog 光电读象仪iconoscope 光电显象管，光电摄象管ICONTT (international conference on nuclear technology transfer) 核技术转让国际会议ICP (integrated circuit package) 集成电路组件ICPS (integrated control and protection system) 集成控制与保护系统ICRP (International Commission on Radiological Protection) 国际辐射防护委员会ICU (instruction control unit) 指令控制器ICW (interrupted continuos wave) 被中断的连续波id. (idem) 同上，同前ID (identification point) 识别点，标识点ID (indicating device) 指示器ID (information distributor) 信息分配器ID (inside diameter) 内径i.d. (inside diameter) 内径ID (instruction decoder) 指令译码器ID (item description) 项目说明IDA (indirect data address) 间接数据地址IDA (input data assembler) 输入数据汇编程序IDA (International Development Association) 国际开发协会IDAC (interconnecting digital-analog converter) 转接数字模拟转换器IDB (Inter-American Development Bank) 泛美开发银行IDC (interest during construction) 建设期利息IDCOR (industry degraded core rulemaking) 工业界退化堆芯规则制定IDCT (indirect dry cooling tower) 间接空冷塔idea 概念；想法ideal 理想的ideal black body 绝对黑体，理想黑体ideal burning 理想燃烧ideal circulation 理想环流ideal climate 理想气候ideal code 理想码ideal coding 理想编码ideal combustion 理想燃烧ideal condition 理想状态ideal cycle 理论循环，理想循环ideal (thermal) cycle efficiency 理想[热]循环效率ideal DC machine 理想直流电机ideal dielectric 理想介质ideal drag 理想阻力ideal efficiency 理论效率，理想效率ideal enthalpy drop 理想焓降，等熵焓降ideal exhaust velocity 理想排气速度ideal flow 理想流动ideal fluid 理想流体ideal fluid theory 理想流体理论ideal focusing field 理想聚焦场ideal frequency domain filter 理想频域滤波器ideal gas 理想气体ideal gas law 理想气体定律ideal-gas temperature scale 理想气体温标idealized characteristic 理想化特性idealized fluid 理想流体idealized fluidization 理想流态化idealized stratified bed 理想分层床ideal jet velocity 理想射流速度ideal line 理想线路，无损耗线路ideal liquid 理想液体ideal load 理想负荷，理想负载ideal mixing stage model 理想混合级模型ideal network 无损耗网络ideal paralleling 理想并车，准同步并车(发电机)ideal plasma 理想等离子体ideal power 理想功率ideal power output 理想功率输出ideal reactor 理想反应器ideal receiver 理想接收机ideal rectifier 理想整流器ideal refrigeration cycle 理想致冷循环ideal regenerative cycle 理想回热循环ideal separation factor 理想分离系数ideal superconductor 理想超导体ideal synchronizing 准同步ideal synchronous machine 理想同步电机ideal thermodynamic efficiency 理想热力学效率ideal thrust coefficient 理想推力系数，理论推力系数ideal thrust equation 理论推力方程ideal time domain filter 理想时域滤波器ideal transformer 理想变压器；理想变换器ideal value 理想值ideal Venturi 理想文丘里管ideal voltage amplifier 理想电压放大器ideal working substance 理想工质idem 同上，同前I-demodulator I信号解调器identical 相同的，相等的；恒等的identically priced 价格相同的identical order 同序[的]identifiable 可辨认的identification 识别，鉴别，辨识，鉴定，证实；标志，符号，标记；表示法identification code 识别码identification division 识别部分，标识部分identification equipment 识别设备，识别装置identification light 标志灯identification mark 识别标志，识别符号identification number 标识号，编号identification of phase 物相鉴定，相位鉴定identification of position 位置识别identification point 识别点，标识点identification section 识别部分，标识部分identification stamp 专用戳记identification switch 识别开关identification threshold 识别阈identified leakage 识别泄漏，查明的泄漏identifier 识别符号，标志符号，标识符；识别器identifier circuit 识别电路identify 辨别，辨认，鉴定；使等同identify code 识别码identity 同一性；恒等式identity certificate 身份证明书identity document 身份证件identity of views 观点一致identity tag 识别标志IDF (induced draft fan) 引风机IDF (integrated data file) 综合数据文件IDFT (inverse discrete Fourier transform) 离散傅里叶逆变换IDI (improved data interchange) 改进的数据交换idioelectric 非导体的，能摩擦生电的idiostatic 同[电]位差的，同势差的idiostatic method 同位差连接法，同势差连接法I display I型显示器，径向圆形扫描三度空间显示器idle 空转的，空载的，备用的，闲置的，无效的，无功的idle bar 死[元件]导条，起动笼条，无载导条idle battery 无载电池，闲置电池idle boiler 停用锅炉idle capacity 空转功率；空载耗汽量；备用容量，备用功率idle circuit 空载电路，空闲电路idle coil 空置线圈，死线圈idle component 无功分量，无功部分idle condition 空载工况，空载条件idle contact 空触点idle control 惰转调节idle current 空转电流，空载电流；无功电流，无效电流idle frequency 中心频率，未调制频率idle gear 惰轮，空转轮；中间齿轮idle hour 停机时间，惰走时间idle interval [换向器]闭锁期间idle line 空线，空转idle loss 空转损失idle motion 空转，空载idleness 空闲时间，空闲率idle operator lamp 空位表示灯idle period 停运时间；无功周期idle position 空转位置，空载位置idler 空转轮，惰轮，拉紧皮带轮，托辊idle revolution 空转转速idler revolution 空转轮转速idle running 空转idle-running time 空转时间idler valve 空载阀，止回阀idler wheel 空转轮，惰轮idle speed 空载转速idle-speed adjustment 怠速调整，空转调整idle state 闲置状态，空载状态idle stroke 空行程，空冲程idle time 惰走时间，惰转时间，空载时间，空闲时间，停机时间idle trunk 空中继线idle unit 空转机组，备用机组idle wire 空线idle work 虚功IDLH (immediately dangerous to life or health) 对生命与健康有即刻危险idling 空转，空载，惰走，惰转；闲置；慢车；无效，无功idling condition 空载工况，空载状态idling curve 惰走曲线idling cut-off 空载切断idling frequency 无效频率，空载频率idling loss 空载损失，低速损失idling speed 空转速度idling time 停机时间，空转时间idometer 测量仪表，探测仪IDP (industrial data processing) 工业数据处理IDP (integrated data processing) 集中数据处理，集总数据处理，综合数据处理IDR (integrated dry route) 一体化干燥法IDS (identification section) 识别部分，标识部分IDS (interim decay storage) 临时衰变贮存IDT (initial deformation temperature) 初始变形温度i.e. (id est) 即，就是IE (initiating event) 触发事件，初始事件IEA (International Energy Agency) 国际能源机构(属OECD)IEC (International Electrotechnical Commission) 国际电工委员会I-E characteristic 电流-电压特性IED (instrument electrical diagram) 仪表电气图IED (instrument engineering diagram) 仪表工程图IEEE (Institute of Electrical and Electronics Engineers) 电气和电子工程师协会(美)IEL (information exchange list) 信息交换表IE Office of Inspection and Enforcement 美国核管会检查与执行局IF (instruction fetch) 指令取出IF (intermediate frequency) 中频IFB (inlet flow blockage) 进口流阻塞IFC (International Finance Corporation) 国际金融公司IFCC (incremental fuel cycle cost) 增量燃料循环成本IFDH (in-service forced derated hour) 强迫降低出力运行小时IFM (intermediate flow mixer) 中间流量混合器IFM (ionic flame monitoring) 电离式火焰监察IFR (integral fast reactor) 一体化快中子[反应]堆IFR (internal function register) 内部操作寄存器；状态字寄存器IFRU (interference rejection unit) 抗干扰装置IFSMTF (international fusion superconducting magnet test facility) 国际聚变超导磁铁试验设施(美国) IFT (ignition fuel trip) 点火燃料跳闸IFT (ignitor fuel trip) 点火器燃料跳闸IF transformer 中频变压器IG (insulated gate) 绝缘栅IGA (intergranular attack) 晶间腐蚀IGCC (integrated gasification combined cycle) 整体煤气化燃气蒸汽联合循环IGFET (isolated gate field effect transistor) 绝缘栅场效应晶体管IGMOSFET (isolated gate MOS field effect transistor) 绝缘栅金属氧化物场效应晶体管igneous rock 火成岩ignifluid boiler 烧可燃性流体锅炉ignifluid process 烧可燃性流体法ignitability 着火性；可燃性ignitable 可燃的ignite 点火，引燃，发火，点燃ignited residue 烧余残渣igniter(-tor) 点火器，点火极ignitibility 可燃性igniting point 着火温度，着火点igniting torch 点火炬，点火喷燃器ignition 着火，点火，引燃，发火；灼热；发火装置ignition accumulator 点火蓄电池ignition advance 提前点火ignition-aid burner 点火喷燃器ignition anode 点火[阳]极，引燃[阳]极ignition arch 点火拱ignition belt 燃烧带，引燃带ignition charge 点火器充电ignition circuit 点火电路，引燃电路ignition coil 点火线圈ignition current 点火电流ignition device 点火设备，点火装置ignition energy 点火能量ignition fuel trip 点火燃料跳闸ignition hazard 着火危险ignition heat 着火热，燃烧热ignition lock 点火开关ignition loss 点火损失ignition magneto 点火用磁电机ignition muffle 点火马弗炉ignition pin 点火电极，发火针ignition plug 火花塞ignition point 着火温度，着火点，燃烧点，引燃点，燃点ignition range 着火范围ignition residue 烧余残渣ignition spark 点火火花，引燃火花ignition spark detector 点火火花探测器ignition switch 点火开关ignition system 点火系统ignition temperature 着火温度，燃点ignition torch 点火炬，点火棒ignition voltage 点火电压，引燃电压ignition wire 点火线ignitor 点火器，点火装置ignitor control 引燃极控制ignitor discharge 点火极放电ignitor electrode 引燃极ignitor fuel trip 点火器燃料跳闸ignitron 点火管，点火器，引燃管；放电管；水银半波整流器ignorance 不知，无知ignorance factor 不知因子IGS (industrial graphic display system) 工业图形显示系统IGSC (intergranular stress corrosion) 晶间应力腐蚀IGSCC (intergranular stress corrosion crack) 晶界应力腐蚀裂纹IGV (inlet guide van) 进口导翼IH (indirect heating) 间接加热IH (inverted hour) 逆时针的；倒时数IHE (intermediate heat exchanger) 中间换热器I-head engine 顶阀发动机，I形气缸头发动机IHF (inhibit halt flip-flop) 禁止停机触发器IHS (in-house standard) 内部标准，厂内标准IHSI (induction heating stress improvement) 感应加热应力改善[技术] IHTS (intermediate heat transport system) 中间热传输系统IIB (International Investment Bank) 国际投资银行IIIL (isoplanar integrated injection logic) 等平面集成注入逻辑IIL (integrated injection logic) 集成注入逻辑IIP (incident investigation program) 事故调研计划IIT (incident investigation team) 事故调查组IIU (input interface unit) 输入接口装置IL (ignition loss) 点火损失IL (indicating light) 指示灯ILAS (interrelated logic accumulating scanner) 相关逻辑累加扫描器ILC (instruction length code) 指令长度码ILC (International Law Commission) 国际法委员会Ilgner set 带飞轮的直流发电机-电动机组，伊格尔纳型机组Ilgner system 带飞轮的直流发电机-电动机变速系统，伊格尔纳系统ill-effect 恶果illegal action 非法行为illegal drug 非法药物illegal nature 非法性质illegal operation 非法操作illegal trade 非法贸易illite 伊利石，伊利水云母illumiance [光]照度illuminance 光照度，照明度illuminant 发光体，发光物，光源；照明装置；发光的illuminate 照明；说明；装饰illuminated 照明的illuminated circuit diagram 照明电路图，照明线路图illuminated dial 照明度盘illuminating apparatus 照明器illuminating line 照明线路illumination 照明；光照度；亮度，辉度；说明illumination curve 照度曲线illumination distribution board 照明配电盘illumination engineering 照明工程，照明技术illumination factor 照明系数illumination level 光照水平，照度级illumination load 照明负荷illumination measurement 照明测量illumination photometer 照度计illumination photometry 照度测定illumination standard 照明标准illuminator 发光器；照明装置；反光镜illuminometer 光照度计illustrate 用图说明；举例说明illustrated catalogue 附图产品目录illustration 插图；注解；说明；实例illustrative 说明性的，特征性的；直观的ilmenite type electrode 钛铁矿型焊条ILSW (interrupt level status word) 中断级状态字I&M (inspection and maintenance) 检查与维修image brightness 图象亮度image channel 图象通道image converter 变象器，光电图象变换器image converter tube 变象管；光电图象变换管image data 图象数据image deburring 消除图象模糊image detect 图象缺陷image diaphragm 图象屏image display 图象显示image distance 像距image distortion 图象畸变image filtering 图象滤波image force model 像力模型image formation 成象image frequency 象频，视频，镜频image frequency interference 镜频干扰，象频干扰image hologram 图象全息图image impedance 影像阻抗，对等阻抗，镜象阻抗，对象阻抗image intensifier 图象增强管image intensifier gamma-ray camera 影象增强γ射线照相机image interference 图象干扰，镜象干扰image location 图象位置image method 镜象法image minification 图象缩小率image modulation 象频调制image motion compensation 图象运动补偿image of system 系统的映射image orthicon 超正[析]摄象管，移象正[析][摄]像管image output transformer 图象信号输出变压器image parameter 图象参数image processing 图象处理image quality indicator 图象质量指示器image reactor 镜象[反应]堆，虚[反应]堆image recognition 图象识别image reconstruction 图象再现image restoration 图象恢复image sharpness 图象清晰度image shield 镜象屏蔽image storage array 影像存储阵列image storage device 图象存储设备image storage tube 图象存储管image theory 镜象原理imaginary 虚数的；虚的，假想的；虚数imaginary accumulator 虚数累加器imaginary axis 虚数轴，虚轴imaginary circle 假想切圆imaginary component 虚部；无功部分，无功分量imaginary hinge 虚铰imaginary load 假想荷载，虚载imaginary loading 无功负载，虚负载imaginary number 虚数imaginary part 虚部，虚数部分imaginary quantity 虚量imaginary unit 虚数单位imbalance 不平衡，失衡，不稳定imbed 埋置，放入，埋入，嵌入imbedded 嵌镶的imbedded temperature-detector 埋入式测温器，埋入式温度计imbedded winding 嵌入的绕组，下线后的绕组imbedding method 嵌入法imbibition 吸入，吸收，吸液imbricated winding 链形绕组IMC (image motion compensation) 图象运动补偿IMDH (in-service maintenance derated hours) 维护降低出力运行小时IMF (International Monetary Fund) 国际货币基金组织Imhoff cone 英霍夫锥形管imidazole 咪唑[C3H4N2]iminodiacetic acid 亚氨二醋酸[(CH2COOH)2NH]IMIS (integrated management information system) 综合管理信息系统imitate 模拟，模仿，仿制imitation 模仿，仿制器，仿造品imitation marble 人造大理石，仿云石imitation stone 人造石imitator 模拟器；仿造者immature 未成熟的immature slug flow 未发展的涌节流immeasurable 不能测量的，不可计量的，无边的immediacy 瞬时性，暂时性，直接immediate 直接的，立即的，最接近的immediate access 立即访问，快速存取immediate access circuit 快速投入电路immediate-access memory 快速存储器；快速存取存储器immediate address 立即地址，零级地址immediate delivery 立即交货immediate destination 直接目的地immediate environment 直接环境immediate operand 立即操作数immediate operation use 立即操作用immediate oxygen demand 直接需氧量immediate participation guarantee contract 立即参与保证合同immediate passivation 快速钝化immediate payment 即时付款immediate processing 立即处理，快速加工immerse 浸渍，浸没，沉入，浸入immersed heat transfer surface 沉浸受热面immersed method 水浸法(超声探伤)immersed superheater 沸腾层过热器(沸腾炉)immersed tube 沉浸管immersible concrete vibrator 插入式混凝土振捣器immersible motor 浸入型电动机，潜水电动机immersible switchgear 浸入式开关装置，潜水开关装置immersion 浸没，浸渍，水浸；沉入；埋入式的immersion coating 化学涂层，电化学涂层immersion cooler 浸入式冷却器immersion counter 浸入式计数管immersion depth 浸没深度immersion dose 浸没剂量immersion heater 浸入式加热器immersion heat exchanger 浸入式热交换器immersion method 油浸法(光纤)immersion plate 浸入板immersion plating 化学浸镀immersion probe 液浸探头immersion pyrometer 埋入式高温计immersion technique 浸没法(超声探头以水作缓冲液)immersion test 浸没[探漏]试验immersion thermocouple 埋浸式热电偶，埋入式热电偶immersion ultrasonic testing 浸入式超声检查immersion vibrator 插入式振捣器imminent 急迫的，迫切的，即将来临的immiscibility 不溶混性，不混和性，难混溶性immiscible fluid 不混合流体immiscible solvent 不混溶溶剂immittance 导抗，阻纳immix 混合，搀和immobile 不动的，固定的，静止的immobile ion exchange site 不移动的离子交换基immobilization (-sation) 固定，降低流动性；阻塞，堵塞immobilized enzyme 固定化酶immobilize waste 固化废物(例如与水泥混合)immoderate 过度的，过分的，不适中的，不合理的immovable 不动的；不变的，静止的immune 免疫的；不敏感的immunity 不敏感性，抗扰性，免除性immunity to interference 抗干扰，不受干扰IMP (industrial management program) 工业管理程序impact 碰撞，冲击，冲力；影响；压紧IMPACT (inventory management program and control technique) 库存管理与控制技术impact acceleration 碰撞加速impact air pressure 气流冲击压力impact allowance 冲击留量；冲击容许量impact bending test 冲击弯曲试验impact breaker 锤击式破碎机impact brittleness 冲击脆性impact burner 冲击式喷燃器impact coefficient 冲击系数impact counter system 冲击计数系统impact crusher 锤击式破碎机impact current 冲击电流impact ductility 冲击韧性impact ductility test 冲击韧性试验impact dust collector 冲击式除尘器impact excitation 冲击励磁；冲击激励；碰撞激发impact exciter 冲击励磁机，强行励磁机impact factor 冲击系数，碰撞系数impact failure 冲击损坏impact fluorescence 撞击萤光impact fracture 冲击断口，冲击断裂impact generator 冲击发电机；冲击电压发生器impaction 冲击；压紧impact ionization 碰撞电离impaction range 冲击量程impact load 冲击负荷，冲击负载，突加负载impact loading 冲击荷载impact mill 竖井式磨煤机，锤击式磨煤机impact noise 碰撞噪声impactometer 冲击仪impactor 冲击器；撞击[取样]器impact plate 撞击板；反射板impact potential 冲击电势，冲击电位impact pressure 冲击压力，动压力impact printer 冲击式打印机impact recorder 冲击记录器impact resistance 冲击阻力impact screen 振动筛impact shock 冲击震动impact strength 冲击强度，冲击值，冲击韧性；抗冲强度impact stress 冲击应力impact temperature 滞止温度impact test 冲击试验impact tester 冲击试验器impact testing 冲击试验impact toughness 冲击韧性impact transition temperature (金属)从延性断裂到脆性断裂的转变温度impact tube 全压管，冲压管impact value 冲击值impact wave 冲击波impair 削弱，损伤，损害，减少；奇数impairment 损害，减少，削弱，损伤，毁损，减损，毁坏imparity 不同，不等，不均匀impassable trench 不通行沟impedance 阻抗，全电阻impedance analysis 阻抗分析impedance angle 阻抗相角impedance bond 阻抗搭接impedance bridge 阻抗电桥impedance-capacity coupled amplifier 阻抗电容耦合放大器impedance characteristic 阻抗特性impedance chart 阻抗圆图impedance circle 阻抗圆impedance coil 扼流圈，电抗线圈impedance compensator 阻抗补偿器impedance conversion 阻抗变换impedance converter 阻抗变换器impedance coupling 阻抗耦合impedance diagram 阻抗图impedance drop 阻抗压降impedance-drop test 阻抗压降试验；短路试验impedance earthed [neutral] system [中性点]阻抗接地系统impedance factor 阻抗系数impedance function 阻抗函数impedance grounded [经]阻抗接地的impedance kilovolt-amperes 阻抗千伏安impedance locus 阻抗轨迹impedance loss 阻抗损耗，负载损耗impedance matching 阻抗匹配impedance-matching load box 阻抗匹配负载箱impedance-matching transformer 阻抗匹配变压器impedance matrix 阻抗矩阵impedance meter 阻抗计impedance method 阻抗法impedance muffler 阻抗复合消声器impedance noise 阻抗噪声impedance of slot 槽阻抗impedance operator 阻抗算子impedance protection 阻抗保护[装置]impedance relay 阻抗继电器impedance spectrum 阻抗谱impedance starter 阻抗起动器impedance-time relay 延时阻抗继电器impedance transformer 阻抗变换器impedance triangle 阻抗三角形impedance unbalance 阻抗失衡，阻抗不平衡impedance vector analysis system 阻抗矢量分析法impedance void meter 阻抗空泡计impedance voltage 阻抗电压impede 阻碍，阻止，妨碍impedometer 阻抗测量仪，阻抗计impedor 二端阻抗元件，阻抗器impellent 推动力，推进器；推进的impeller 叶轮impeller blade 叶轮叶片，动叶片impeller eye 叶轮入口impeller hub 叶轮轮毂impeller hub ratio 叶轮轮毂比impeller inlet guide vane 叶轮进口导向叶片impellerless burner 直流式喷燃器impeller pump 叶轮泵impeller shaft 叶轮轴impeller suction 叶轮吸入口impeller vane 轮叶，桨叶impeller wheel 叶轮impelling power 推进力impenetrability 不可贯透[性]，不能贯穿imperfect 不完全的，未完成的，不完善的，有缺陷的imperfect combustion 不完全燃烧imperfect contact 不良接触imperfect dielectric 非理想介质imperfect earth 接地不良imperfect gas 非理想气体，实际气体imperfection 不完整[性]，缺陷，缺点imperfect mixing 不完全混合，非理想混合imperfect tape 缺陷磁带，缺陷带impermanent 非永久的，暂时的impermeability 不渗透性，不透水性，防水性impermeable 不渗透的，不可渗透的，防水的，不透水的impermeable barrier 不透水层impermeable layer 不透水层impermeable rock 不透水岩impermeable seam 不透水层impermeable stratum 不透水层impermissible 不许可的impertinent 不恰当的，不适合的，无关的impervious 不可渗透的，不透水的，透不过的impervious barrier 防渗层impervious layer 不透水层impervious machine 密封型电机imperviousness 不透过性；不透水性impervious rolled fill 不透水的碾压填土impervious stratum 不透水[地]层impervious to moisture 防潮的impetus 动力；刺激；冲击，冲量impinge 冲击，碰撞impingement 冲击，碰撞impingement angle 冲击角，入射角impingement attack 磨损，侵蚀，冲蚀，渍蚀impingement cooling 冲击冷却impingement corrosion 冲击腐蚀impingement plate scrubber 板式冲击除尘器impingement ring 档油环impingement separator 油水分离器impinging neutron 撞击中子implement 工具，用具，器械，仪器；履行，执行，实现implementation 工具，器具；执行程序；实施implementation of contract 履行合同implementation schedule 执行进度表，工程程序表implication 蕴含，隐含，含蓄implicit 隐含的implicit computation 隐函数法计算implicit definition 隐定义implicit differentiation 隐函数微分implicit function 隐函数implicit function generation 隐函数发生implicit function theorem 隐函数定理implicit solution 隐函数解implicit synchronizing signal 内隐同步信号implosion 内爆，内燃implosion test [后汽缸]刚性试验imporosity 无孔性，不透气性import 输入，进口Import Advisory Committee 进口咨询委员会importance 重要性，重大，显著；价值importance function [中子]价值函数import and export 输入和输出import and export corporation (company) 进出口公司import and export duty and tax 进出口关税和其他税项import and export merchant 进出口商import and export restrictions 进出口限制importation forbidden 不准进口import authorization 进口许可import bill 进口汇票import commission house 进口代理商import commitment 进口承诺import commodity 进口商品import control 进口管制import declaration 进口声明书，进口报关单import deposit 进口保证金import duty 进口税import duty memo 海关进口税缴纳import entry 报关importer 进口商importers' agent 进口代理人importers' association 进口商协会import license 进口许可证import permit 进口许可import regulation 进口条例import restraints 进口限制imports 进口货物import surcharge 进口附加税import trade 进口贸易import value 进口值imposed deformation 外加变形imposed load 作用荷载，强加荷载impossibility 不可能性impotable water 非饮用水impounded body 静止水体，蓄水池impounding reservoir 蓄水池，水库impoundment 蓄水，积水；蓄水池imprecise terms 不明确的条文impregnant 浸渍剂impregnate 渗透，浸透，浸渍；浸渍的，浸透的impregnated 浸透的，饱和的；嵌装的impregnated cable 浸渍电缆impregnated carbon 浸渍碳棒impregnated coil 浸渍线圈impregnated glass cloth 浸渍玻璃布impregnated graphite 浸渍石墨impregnated paper 浸渍纸impregnated paper insulated 浸渍纸绝缘的impregnated winding 浸渍绕组impregnated wood 浸渍木材impregnate with bitumen 浸沥青，浸胶impregnate with varnish 浸漆impregnating bath 浸渍池，浸渍槽impregnating compound 浸渍胶，复合胶，浸渍剂impregnating equipment 浸渍设备impregnating machine 浸渍机impregnating mechanism 浸渍设备impregnating paper 浸渍纸impregnating resin 浸渍树脂impregnating varnish 浸渍漆impregnating vessel 浸渍槽，浸胶槽impregnation 浸渍，浸透；浸染；注入impregnation crack detector 浸透式探伤器impregnation liquid 浸渍液impregnation of insulation 绝缘浸渍impregnation technology 浸渍工艺impregnator 浸渍机，浸渍设备impressed current 外加电流impressed electromotive force 外加电动势impressed pressure 外加压力impressed torque 外加转矩impressed voltage 外加电压impression of legal seal 盖印鉴imprimitive 非本原的，非原始的imprinter 印刷器，刻印器improper 不适当的，不合理的，不正常的；错误的improper integral 反常积分improper packing 包装不良improper shipment 装运不当improper ventilation 通风不良improve 改善，改进improved nuclear material 精制的核材料improvement 改进，完善化improvement factor 改进系数，改进因子improvement patent 改进专利imprudent expenditure 不适宜的支出impulsator 脉冲发生器，脉冲传感器impulse 冲击，冲动，撞击；脉冲，冲量；推动；激磁，激发；推力，冲力impulse action 冲动作用impulse amplitude 脉冲振幅impulse analyzer 脉冲分析器impulse attenuation 脉冲衰减impulse blade 冲动式叶片impulse blading 冲动式叶片impulse breakdown 冲击击穿impulse breaker 冲击开关impulse cascade 冲动式叶impulse circuit 脉冲电路impulse circuit-breaker 冲击断路器impulse code 脉[冲]码impulse-code modulation 脉冲编码调制impulse coding 脉冲编码impulse-conservation equation 冲量守恒方程impulse control 脉冲控制impulse counter 脉冲计数器impulse current 脉冲电流；冲击电流impulse current relay 脉冲电流继电器impulse discharge 冲击放电impulse duration 脉冲宽度，脉冲[持续]时间impulse duration system 脉冲时间系统impulse equation 冲量方程impulse excitation 脉冲激发，脉动激励impulse exciter 冲击激励器impulse factor 冲击因数impulse flashover 冲击闪络impulse flashover voltage 冲击闪络电压impulse force 冲击力impulse-forced response 脉冲强迫响应impulse frequency 脉冲频率impulse frequency telemetering 脉冲频率遥测[法]impulse front 脉冲前沿impulse function 脉冲函数impulse fuse 冲击熔丝impulse generator 脉冲发生器，冲击电压发生器，脉冲振荡器impulse hunting 脉冲摆动，脉冲振荡impulse inertia 冲击惯性impulse insulation level 冲击电压绝缘水平impulse law 冲量守恒定律impulse level 冲击水平impulse load 冲击负荷impulse machine 脉冲发生器impulse measurement 冲击测量impulse mechanical strength 冲击机械强度impulse meter 脉冲计数器，脉冲计算器impulse method 脉冲法impulse noise 脉冲噪声；冲击干扰；冲击噪声impulse noise limiter 脉冲噪声限幅器impulse of electron current 电子流脉冲impulse oil pressure 脉动油压impulse oscillograph 脉冲示波器impulse overvoltage 冲击过电压impulse phase-locked loop 脉冲锁相环impulse power 脉冲功率impulse protection level 冲击保护水平(避雷器的) impulser 脉冲发生器，脉冲传感器，脉冲发送器impulse ratio 脉冲比impulse reactance 冲击电抗impulse-reaction turbine 冲动反动式汽轮机impulse recorder 脉冲记录器，脉冲记录仪impulse regenerator 脉冲再生器impulse register 脉冲寄存器；脉冲计数器impulse regulator 脉冲调节器impulse relay 脉冲继电器impulse repeater 脉冲重发器impulse response 脉冲响应impulse response function 脉冲响应函数impulse scaler 脉冲计数器impulse section blade 冲动式叶片impulse sender 脉冲发送器impulse sequence 脉冲序列impulse set 冲动式机组impulse shape 脉冲波形impulse shaper 脉冲形成器impulse signal 脉冲信号impulse source 脉冲源impulse sparkover 脉冲闪络，冲击闪络impulse sparkover characteristics 冲击闪络特性impulse sparkover voltage 冲击闪络电压impulse speed 脉冲速度impulse stage 冲动级impulse starting 脉冲起动impulse steam trap 脉冲式疏水器impulse stepping motor 脉冲步进电动机impulse strength 脉冲强度，冲击强度impulse stress 冲击应力impulse summation 脉冲相加impulse system 脉冲系统impulse test 冲击试验；脉冲试验impulse time margin 脉冲时间裕度impulse timer 脉冲时间继电器，脉冲定时器impulse transformer 脉冲变压器impulse transmission 脉冲传输impulse transmitting relay 脉冲发送继电器impulse turbine 冲动式汽轮机，冲击式水轮机impulse-type relay 脉冲式继电器impulse-type stage 冲动级impulse-type steam turbine 冲动式汽轮机impulse-type telemeter 脉冲式遥测计impulse-type voltage regulator 脉冲式电压调整器impulse voltage 冲击电压；脉冲电压impulse-voltage generator 冲击电压发生器；脉冲电压发生器impulse voltage oscilloscope 脉冲电压示波器impulse voltage test 冲击电压试验impulse wave 冲击波，脉冲波impulse-wave test 冲击波试验impulse welding 脉冲焊接impulse wheel 冲动式叶轮impulse withstand level 耐冲击水平impulse withstand test 耐冲击试验impulse withstand voltage 冲击耐[电]压impulsing 发送脉冲；脉冲激励impulsion 冲击，冲动；推动；脉冲，冲量，推力impulsive discharge 脉冲放电impulsive load 脉冲荷载impulsive noise 冲击噪声，脉冲干扰impulsive sound 冲击声impure 不纯的，不洁的，有杂质的impurity 杂质，夹杂物；污染；有杂质的，不纯洁的impurity concentration 杂质浓度impurity conduction 杂质导电impurity damage 污染损伤；杂质损性impurity in ionized state 离子态杂质impurity level 杂质水平impurity semiconductor 杂质半导体imput 输入，输入功率，输入电压，输入端imputed cost 应负成本imputed income 应计收入，估算收入IMS (information management system) 信息管理系统IN (inlet) 进口IN (inlet valve) 进汽阀inaccessible area 不可接近区域，不可进入区域inaccessible reactor building 不可进入的反应堆厂房inaccuracy 不精确性，偏差，不准确度，误差inaccurate 不精密的，不准确的，有误差的inaction 故障，停车；无行动，无作用；不活泼，不活动inaction period 无作用期间；钝化周期inactivate 钝化inactivation 钝化[作用]inactivation cross-section 钝化截面，非活化截面inactive 不活泼的；钝性的；非放射性的；非活性的inactive alkali 惰性碱inactive area 非放[射性]区，非活性区inactive component 非能动部件，无[外]源设备；从动设备inactive fault 不活动断层inactive gas 惰性气体inactive laboratory 非放[射性]实验室，冷实验室inactive state 不活泼状态，待用状态，关闭状态inactive substance 非活性物质inactive test 非放[射性]试验，冷试验inactive time 无效时间，不可用时间inactive waste 非放[射性]废物inactivity 钝化，使失去活性inadequacy 不适当，不合适；不足，不够inadequate trip 误动作inadvertent maloperation 偶然误动作；意外操作inadvertent rod withdrawal 误提棒inadvertent trip 误动作；乱真跳闸inapplicable 不能应用的，不适用的inappreciable 微不足道的，不足取的inapprehensible 难以理解的，难了解的inappropriate 不适当的，不相称的inapt 不适当的，不合适的，不熟练的，拙劣的inarmoured 非铠装的inarmoured cable 未铠装电缆。

2008Performance of Transgenic Potato Containing the Late Blight Resistance Gene RB

A number of wild, tuber-bearing Mexican potato species have been reported to carry valuable resistance to late blight, thus providing a potential source of resistance for breeding programs (1,6). Eleven racespecific R genes have been identified in the wild potato species S. demissum and introgressed into cultivated potato using classical breeding methods (12,22,25). Unfortunately, virulent races of P. infestans have rapidly overcome the majority of these 11 R genes in most potato-growing regions (5,25). A major late-blight-resistance gene previously was identified in the wild potato species S. bulbocastanum and integrated into cultivated potato, S. tuberosum, through somatic fusion (8). The resistance gene, called RB, subsequently was cloned and found to belong to the largest class of R genes, those that encode proteins with a nucleotide binding site and leucine rich repeats (NB-LRR; 19,23). A long-range polymerase chain reaction (PCR) product including the gene coding region of RB, as well as approximately 5 kb of upstream regulatory sequences, was stably integrated into S. tuberosum using Agrobacteriummediated transformation (19). Somatic fusions and transgenic plants containing

2.04.10.-.Dermatophilosis 嗜皮菌病

C H A P T E R2.4.10.D E R M A T O P H I L O S I SSUMMARYDermatophilosis (also known as streptothrichosis) is an exudative, pustular dermatitis that mainlyaffects cattle, sheep and horses, but also goats, dogs and cats, many wild mammals, reptiles and,occasionally, humans. The severe disease in ruminants is promoted by immunomodulatory effectsinduced by infestation with the tick, Amblyomma variegatum.Laboratory diagnosis of dermatophilosis depends on the demonstration of the bacteriumDermatophilus congolensis in material from the skin or other organs. Sites other than the skin arerarely affected.Identification of the agent:Dermatophilus congolensis normally affects the epidermis, causing theformation of scabs. It may be demonstrated in smears made from scabs emulsified or softened inwater or in impression smears from the base of freshly removed adherent scabs. The organism isGram positive, but its morphology is more readily appreciated in smears stained with Giemsa. Instained smears, the organism is seen as branching filaments containing multiple rows of cocci. Thischaracteristic appearance is diagnostic. In wet or secondarily infected scabs, only free cocci may bepresent, so that staining by immunofluorescence is necessary. Dermatophilus congolensis isdemonstrated in histopathological sections by Giemsa staining or by immunofluorescence.Dermatophilus cheloniae may be found in crocodiles, chelonids and cobras.Isolation of D. congolensis from freshly removed scabs is straightforward, but the organism isreadily overgrown by other bacteria. When cultured from contaminated sites, special techniquesinvolving filtration, chemotaxis, or selective media are necessary.Demonstration and identification of D. congolensis by immunofluorescence is a reliable and verysensitive method of diagnosis, but requires that laboratories make their own diagnostic antisera asthese are not available commercially. Although antigenic cross-reaction with Nocardia spp. hasbeen reported, this is likely to give only weak fluorescence. Ideally, a monoclonal antibody specificto D. congolensis should be used. Polymerase chain reaction (PCR)-based characterisation hasalso been developed.Serological tests: A variety of serological tests has been used in studies of the epidemiology andpathogenesis of dermatophilosis. Antibody can be demonstrated in all but fetal blood in healthyruminants, but the elevated levels associated with clinical infection can be used to identify animalsthat have been infected with the disease.Requirements for vaccines and diagnostic biologicals: Despite the identification of severalvirulence factors, no vaccines are available currently.A. INTRODUCTIONDermatophilosis (also known as streptothrichosis, or in sheep as ‘lumpy wool disease’) is an exudative, pustular dermatitis that affects mainly cattle, sheep and horses, but also goats, dogs and cats, many wild mammals, reptiles and, occasionally, humans. Dermatophilosis is caused by the bacterium Dermatophilus congolensis, the type species of the genus Dermatophilus, which is a member of the order Actinomycetales. Dermatophilosis is the commonest skin disease of crocodiles in Australia and has an impact on farming of this species (2). It is provoked by Dermatophilus cheloniae, which has also been isolated from chelonids and cobra.There is considerable variation in the clinical appearance of the disease and in the affected areas of the body. Typically, infection gives rise to the formation of dense scabs on the skin, but in certain areas, such as the perineum in ruminants and the pastern in horses, moist lesions with thickened, folded skin may occur. In suchlesions, relatively thin scabs are found. Where lesions are exposed to prolonged wetting, with or without secondary infection, exudative lesions may be present.Scabs characteristically comprise alternating layers of parakeratotic keratinocytes invaded with branching bacterial filaments and infiltrates of neutrophils in serous exudate. This gives a palisaded appearence in stained sections. D. congolensis filaments remain confined to the epidermis and very rarely infect the dermis.Extensive acute dermatophilosis cannot be reproduced easily in experimental conditions. Dermatophilus congolensis itself is not highly pathogenic, and a combination of factors is necessary for the development of clinical lesions. Malnutrition, intense rainfalls and mechanical traumas have been incriminated as favouring the disease. However, where dermatophilosis has an important economic impact in West and Central Africa as well as on some Caribbean islands, the major risk factor is the infestation by Amblyomma variegatum ticks. Severe disease may be promoted by immunomodulatory effects of saliva secreted during tick bite (1), but the fine underlying mechanisms are not understood. Susceptibility to dermatophilosis is also greatly influenced by the genetic background of ruminant breeds, animals from temperate regions and especially dairy cattle being extremely susceptible when introduced in regions at risk.B. DIAGNOSTIC TECHNIQUES1. Identification of the agenta) Microscopic observationDiagnosis can usually be made by demonstrating the causal organism in scabs from the lesions or in exudate beneath the scabs. The organism has a characteristic microscopic appearance – its septate, branching filaments become longitudinally, as well as transversely, divided to form ribbons of spherical or ovoid cocci, each about 0.5 µm in diameter, in multiple rows. This appearance is diagnostic, provided that cocci are found in transverse rows of four or more, and is readily seen in stained preparations. However, the distinctive formation can be disrupted during the preparation of smears for examination if the material is spread too vigorously over the slide.Impression smears may be made from the moist, concave undersurfaces of freshly removed scabs.Otherwise, thick smears are best prepared from scabs emulsified in sterile distilled water. Alternatively, scabs can be soaked overnight in sterile water or saline to sufficiently moisten them so that the undersurface of the scab can be used to make effective impression smears by firmly pressing this surface on to a microscope slide. Smears are then air-dried, fixed by heating or immersion in methanol for 5 minutes, and stained. The organism stains well in dilute carbol fuchsin or methylene blue stain, but Gram’s stain or, preferably, a 1 in 10 dilution of Giemsa stain for 30 minutes, gives better differentiation in thick smears, the darkly stained D.congolensis contrasting with the paler or pink counterstained background of keratinocytes and neutrophils. Gram staining does not give as good results as Giemsa because it may overstain the background and does not clearly show the characteristic laddering of the coccoid forms.Wet or secondarily infected scabs often contain few, if any, intact filaments, and the organism may not stain Gram positive. In such material, the cocci cannot be differentiated morphologically from other coccoid bacteria, so that staining by immunofluorescence is required. However, specific antisera for immunofluorescence are not commercially available. Thin, heat-fixed smears are used. In difficult cases and when infection of organs other than the skin is suspected, histopathological examination of biopsy or necropsy material is advisable. Giemsa stain or immunofluorescence is used.The characteristic appearance of the lesions and of the organism in smears from typical bovine dermatophilosis makes culture unnecessary in most cases. However, in the rare cases in which a Giemsa-stained smear does not give a definitive result, confirmation of the diagnosis may be made by isolating the bacterium. Cultures are made on blood agar and incubated at 37°C. Growth is accelerated under microaerophilic conditions; rough, usually haemolytic, greyish-yellow colonies, about 1 mm in diameter, are seen pitting the medium after 24 hours. Incubation in air produces similar pinpoint colonies at 24 hours that grow to about 1 mm at 48 hours. The rough colonies are formed by the branching filaments, but continued growth in air stimulates the production of the cocci, which are commonly yellow in colour. Colonies take on a smooth, often yellowish, appearance. The cocci are normally vigorously motile when taken from young cultures. The colonies must be differentiated from Nocardia spp. and Streptomyces spp., neither of which produces filaments that break up into multiple rows of motile cocci.b) CultureFor isolation, material can be streaked out directly from the moist undersurfaces of freshly removed, uncontaminated scabs or from scab emulsions, but the relatively slow-growing D.congolensis is readily overgrown by other bacteria. Special isolation techniques are thus required for contaminated specimens. In most specimens, free cocci, whether motile or not, will be present in emulsions of the material. Filtration of the emulsion through a 0.45 µm membrane filter is usually sufficient to reduce or eliminate contaminants and permits isolation from the filtrate, as described above. Alternatively, Haalstra’s method (4) may be used.Small pieces of scab are placed in a bijou bottle containing 1 ml of sterile distilled water and allowed to stand at room temperature for 3–4 hours. The open bottle is then placed for 15 minutes in a candle jar. Samples of the surface liquid are removed with a bacteriological loop and cultured. The method depends on the release from the scab of the motile cocci of D.congolensis and their chemotropic attraction towards the carbon-dioxide-rich atmosphere of the candle jar. A selective medium consisting of 1000 units/ml of polymyxin B in blood agar can also be used, and is effective when the contaminants are sensitive to this antibiotic.c) Immunological methodsImmunofluorescence staining of smears or tissues is the most reliable and sensitive immunological technique for the identification of D. congolensis antigens and for the diagnosis of dermatophilosis.Polyclonal antibody obtained from animals inoculated with D. congolensis can be easily prepared using standard methods, but there is a risk of possible cross-reaction with some strains of Nocardia spp.Monoclonal antibody to species-specific antigen (5) is preferable. However, monoclonal antibodies have not been widely distributed and validated by interlaboratory tests. Thin, heat-fixed smears of scab emulsions, or impression smears, are stained. Known positive and negative control specimens should always be included.d) Nucleic acid recognition methodsIn absence of extensive genome sequence information, randomly amplified polymorphic DNA methods (RAPD) as well as pulsed-field gel electrophoresis (PGFE) have been used and proved to be useful for the molecular typing of D. congolensis (7). An alkaline ceramidase gene was cloned from RADP fragments, anda polymerase chain reaction (PCR) using primers designed from the nucleotide sequence from this genegave an amplification product with D. congolensis DNA. No amplification product was observed with M bovis,C. propinquum andD. cheloniae, suggesting a possible use in diagnosis or detection of D. congolensis (3).Alternatively, 16S rDNA sequence obtained after amplification can be used to confirm the presence ofD. congolensis.2. Serological testsClinical diagnosis is best performed using the methods described above rather than serological methods. Antibody can be demonstrated in all but fetal blood in healthy ruminants, but levels are raised following clinical infection. The enzyme-linked immunosorbent assay (ELISA) has proved to be a sensitive and convenient assay technique, and elevation of titres above baseline values can be used in epidemiological studies to identify animals that have had the disease (9). The test being based on a crude antigen, cross-reactivity with other bacteria can occur as in immunofluorescence. At present, the ELISA remains as a research and investigation method. Serology, either using ELISA or older methods such as haemagglutination and counter-immunelectro-phoresis, is not used for routine diagnosis of dermatophilosis where direct detection of the bacterium is easy.C. REQUIREMENTS FOR VACCINES AND DIAGNOSTIC BIOLOGICALS Dermatophilus congolensis produces virulence factors such as haemolysin, phospholipases, ceramidases and proteolytic enzymes, which may be used to penetrate the epidermis barrier and interact with the inflammatory response of the host. These virulence factors are considered candidate antigens for vaccines. Research on vaccines for prevention of dermatophilosis has been conducted (6, 10); however, no vaccine is currently available. Research in this domain is hampered by the inability to reproduce the disease experimentally and the poor understanding of skin immunity. Much emphasis has therefore been put on tick control and identification of genetic markers of resistance or susceptibility with promising results in cattle (8).REFERENCES1. A MBROSE N.,L LOYD D.H.&M AILLARD J.C. (1999). Immune responses to Dermatophilus congolensisinfections. Parasitol.Today, 15, 295–300.2. B UENVIAJE G.N.,L ADDS P.W.&M ARTIN Y. (1998). Pathology of skin disease in crocodiles. Aust. Vet. J., 76,357–363.3. G ARCIA-S ANCHEZ A.,C ERRATO C.,L ARRASA J.,A MBROSE C.N.,P ARRA A.,A LONSO J.M.,H ERMOSO-DE-M ENDOZAM.,R EY J.M.&H ERMOSO-DE-M ENDOZA J.(2004).Identification of an alkaline ceramidase gene from Dermatophilus congolensis. Vet. Microbiol., 99, 67–74.4. H AALSTRA R.T. (1965). Isolation of Dermatophilus congolensis from skin lesions in the diagnosis ofstreptothricosis. Vet. Rec., 77, 824–825.5. H OW S.J.,L LOYD D.H.&L IDA J. (1988). Use of a monoclonal antibody in the diagnosis of infection byDermatophilus congolensis. Res. Vet. Sci., 45, 416–417.6. H OW S.J.,L LOYD D.H.&S ANDERS A.B. (1990). Vaccination against Dermatophilus congolensis infection inruminants: prospects for control. In: Advances in Veterinary Dermatology, Volume 1, Von Tscharner C. & R.E.W. Halliwell, eds. Bailliere Tindall, London UK.7. L ARRASA J.,G ARCIA-S ANCHEZ A.,A MBROSE C.N.,P ARRA A.,A LONSO J.M.,R EY J.M.,H ERMOSO-DE-M ENDOZA M.&H ERMOSO-DE-M ENDOZA J.(2004).Evaluation of randomly amplified polymorphic DNA and pulsed field gel electrophoresis techniques for molecular typing of Dermatophilus congolensis. FEMS Microbiol. Lett., 240, 87–97.8. M AILLARD J.C.,B ERTHIER D.,C HANTAL I.,T HEVENON,S.,S IDIBE I.,S TACHURSKI F.,B ELEMSAGA D.,R AZAFINDRAIBEH&E LSEN J.M.(2003).Selection assisted by a BoLA-DR/DQ haplotype against susceptibility to bovine dermatophilosis. Genet. Sel. Evol., 35, 193–200.9. M ARTINEZ D.,A UMONT G.,M OUTOUSSAMY M.,G ABRIEL D.,T ATAREAU J.C.,B ARRE N.,V ALLEE F.&M ARI B.(1993). Epidemiological studies on dermatophilosis in the Caribbean. Rev. Elev. Med. Vet. Pays Trop., 46, 323–327.10. S UTHERLAND S.S.&R OBERTSON G.M. (1988). Vaccination against ovine dermatophilosis. Vet. Microbiol.,18,285–288.** *。

突发公共卫生事件中的伦理矛盾及其缓解策略——基于新冠肺炎疫情

网址与投稿:http://yxllx.xjtu-edu-co突发公共卫生事件中的伦理矛盾缓解策略——基于新冠肺炎疫情防控的思考姜荔雯（上海师范大学马克思主义学院，上海200234,jlycheel004@）〔摘要〕由于突发公共卫生事件具有意外性、复杂性、集聚性、阶段性等特征，因此在防控时会采取一系列诸如隔离、留观等措施，这可能会产生知情同意与应急救援、媒体公开的透明迅速与普通民众的舆情应激、日益提升的健康意识与未病人群的资源占用等之间的伦理问题。

在分析这些矛盾的主要表现后可以发现，通过如下措施能够有效缓解这些矛盾：强化沟通理解、实现个人利益和集体利益相统一，救治回归人性、凸显人文关怀，加强行业监管、切断不实口径，加强健康宣教、引导理性认知。

〔关键词〕突发公共卫生事件；新冠肺炎;伦理矛盾；舆情应激;健康宣教;人文关怀〔中图分类号〕R-052〔文献标志码〕A〔文章编号〕1001-8565(2020)04-0423-05 DOI：10.12026/j.issa.1401-8565.2020.04.14Analysit of Ethical Controdictiont in Public Henlth Emeroencies and Theio Mitination Stroteyies:On the Prwention and Controi of COVID-12JIANG Liwen(Scaod of Marxism,Shandhai Normai University,Shanghai260634,China,E-mli：丿iyciee1004@) Abstroct:As public health emergencies arc usually ckaracterized by llupredicmPUUy,complexity,agglomeration anb staacs:a serins oS measures wilt bc tanen burina prevention and control:suck as isolation anb observation. This may leat to ethical contranictions between informed consent anb emergency rescoc.rapid anb open media Wansparency anb the eeneral puUlic's puUlic opinion stress,idcreasina health awareness,anb resource occupation by don-ill people,which will also intedsify some cenUicts.After adalyzina the main manifestations oS these contra-bictions:this stuUy fouub that these cenWanickons could bc eXectively alleviated thauah the followina measures: idclubina:sWenathenina communication anb understanbina,realizina the unity oS personal anb collective interests: saving and returnina to humanity,highlightina humanistic care,enhancina inbustg supeaision,cottina off amors: anvocatina health education anb euidina rational covnition.Keyword::PuUlic Health Emergencies；COVID-19；Ethical Contabictions；PuUlic Opinion Stress；Health Ebucation；Humanistic Care为了维护人民健康安全,促进经济发展，必须重视公共卫生事件所引发的一系列伦理矛盾问题。

实验室资质认定内审员基础知识

实验室资质认定内审员基础知识第一节常用术语和定义一、管理术语(一) 认证和认可1．认证certification与产品、过程、体系或人员有关的第三方证明。

注：①管理体系认证有时也被称为注册。

②认证适用于除合格评定机构自身外的所有合格评定对象，对合格评定机构适用认可。

2．认可accredtation正式表明合格评定机构具备实施特定合格评定工作能力的第三方证明。

注：认可本身并不赋予实验室批准任何特定产品的资格，但是，当批准机构和认证机构决定是否接受与其业务有关的实验室提供的数据时，认可就可能与这些机构有关。

3．实验室认可laboratory accreditation对校准和检测实验室有能力进行指定类型的校准和检测所做的一种正式承认。

4．实验室认可机构laboratory accreditation body实行和管理实验室认可体系并准予认可的机构。

它是指建立实验室认可制度，并对实验室进行认可的政府或民间团体。

5．实验室评审laboratory assessment为评价校准和检测实验室是否符合规定的实验室认可准则而进行的一种检查。

6．现场评审assessment visit为了对提出申请的实验室是否符合认可准则进行现场验证所做的一种访问。

注：也称为现场访问。

7．(实验室)能力验证(1aboratory)proficiency testing利用实验室间比对确定实验室的检测／校准能力。

注：“实验室能力验证”一词的含义极为广泛，它包括了以下内容：①定性计划——例如要求实验室识别被测物品的某个组分。

②数据转换演练——例如提供给实验室多组数据要求进行处理，以获得进一步的信息。

③单件物品检测——一件物品按顺序送往若干个实验室，并按时返还组织者。

④单项演练——就单一事件，向实验室发送一个被测物品。

⑤连续计划——按规定的时间间隔，连续地向实验室发送被测物品。

⑥抽样——例如要求个人或组织抽取样品，以供进行后续分析。

TA Instruments – 保护蛋白质蛋白质交互的抑制剂发现与特性分析（使用ITC方法）说明

TA Instruments – Application Note__________________________________________________________________________________ Discovery and Characterization of Inhibitors of Protein/ProteinInteractions by ITCArne Schön, PhD and Ernesto Freire, PhDDepartment of Biology, Johns Hopkins UniversityThe inhibition of protein-protein interactions is a major goal in the therapy of different pathological conditions including cancer, inflammation, autoimmune diseases, diabetes, osteoporosis, infection, etc. Since protein-protein interactions play a critical role in biological signaling, the identification and optimization of molecules that inhibit those interactions is a major research objective in the pharmaceutical industry. The number of targets of interest is continuously increasing and range from a vast number of cell surface receptors, such as EGFr, TNFr, and IGFr to other proteins involved in signaling and regulation (1, 2). In the case of HIV infection, for example, the first event is the binding of the viral envelope glycoprotein gp120 to the cell surface receptor CD4 (3, 4). Until now, biologics, i.e. monoclonal antibodies or recombinant versions of ligand proteins and/or soluble regions of the receptors, have defined the therapeutic arsenal aimed at targeting protein/protein interactions. The identification of small molecules that accomplish the same goals has become a new frontier in drug research.Isothermal Titration Calorimetry (ITC) plays a critical role in the identification and characterization of inhibitors of protein/protein interactions (PPI). The identification of PPI inhibitors is fundamentally different to the identification of enzyme inhibitors for which inhibition assays are relatively easy to implement using a variety of approach. For PPI, functional or cell based assays do not reveal the molecular target(s) of molecules identified as active. On the other hand, binding assays alone cannot tell if a binder is also a PPI inhibitor. For PPI inhibitors it is necessary to implement an assay that measures directly the association between the two proteins and its inhibition by the inhibitor candidates. This is the assay where ITC excels.The identification of PPI inhibitors by ITC requires:1. Measuring the binding of the two proteins. This experiment is performed onceand serves as the reference.2. Measuring the binding of the two proteins in the presence of a fixedconcentration of the inhibitor candidates.TA Instruments – Application Note__________________________________________________________________________________3. The characterization of those molecules that score favorably in the PPI inhibitorsscreen is performed by directly measuring the binding of the selected compounds to the target proteins.Measuring Protein/Protein BindingIn this Application Note we will use the binding of the envelope glycoprotein of HIV-1gp120 to the soluble form of the cell surface receptor sCD4 as an example.The reaction cell of the Nano ITC Low Volume (LV) (TA Instruments, New Castle, DE) is filled with 0.17 mL of 4.5 µM of gp120. The injection syringe is filled with a 45 µM solution of sCD4. These protein solutions are equivalent to 0.25 and 2.0 mg/mL respectively. Injection volumes are 2µL in all experiments presented here. In general, with the current instrument precision the protein concentrations can be reduced 3-fold and still obtain accurate results.All protein solutions are in PBS (Roche Diagnostics GmbH, Mannheim, Germany), pH 7.4 with 2 % DMSO. Figure 1 shows the titration of sCD4 into gp120. It is consistent with an association constant, K a, of 1.2 × 108 M-1 or equivalently a dissociation constant K d = 1/K a of 8.3 nM. Furthermore, the binding enthalpy, ΔH, is -38.0 kcal/mol and the entropy contribution to the binding Gibbs energy, –TΔS, is 27.0 kcal/mol (1 cal = 4.184 joules). The thermodynamic signature in the inset provides a visual representation of the magnitude of those contributions to binding. Figure 1. ITC titration of sCD4 into gp120TA Instruments – Application Note__________________________________________________________________________________ The binding of sCD4 to gp120 is characterized by large favorable enthalpy and large unfavorable entropy changes, indicative of a binding reaction associated with a large structuring process. In this case, the binding of sCD4 triggers the folding of intrinsically disordered domains in gp120 (5, 6). Protein/protein binding not associated with large refolding processes are characterized by favorable enthalpy and entropy changes.Screening for InhibitorsThe identification of PPI inhibitors is accomplished by performing the same experiment shown in Figure 1 except that the reaction cell also contains a fixed concentration of an inhibitor candidate. Since initial leads are usually active in the low micromolar range, a good concentration is in the hundreds micromolar range. If a compound inhibits the protein/protein interaction, it will be observed as a decrease in the observed or apparent binding affinity, K app. The magnitude of the decrease can be expressed in terms of the ratio A = K app/K a. If A = 1, then the compound has no effect on the protein/protein interaction. If A<1, then the compound has an inhibitory effect. If all the compounds are screened at the same concentration, then the parameter A suffices to rank them in terms of their inhibitory potency. Sometimes a compound is found that exhibits an A value greater than one. This compound actually increases the binding affinity acting as an agonist of the protein/protein interaction. While most of the time drug developers are searching for inhibitors, we should emphasize that this technology also allows for the identification of PPI agonists.Figure 2 shows a titration similar to the one shown in Figure 1 except that the reaction cell also contains 200µM of NBD-556, a small molecular weight (MW = 337.84) low affinity sCD4/gp120 inhibitor (5, 6). This experiment is consistent with an apparent association constant, K app, of 7.7 × 106 M-1 or equivalently an apparent dissociation constant K d,app = 1/K app of 130 nM, indicating that the presence of the compound significantly reduces the affinity of sCD4 for gp120. The apparent binding enthalpy is -23.0 kcal/mol and the apparent entropy contribution to binding is 13.6 kcal/mol. The thermodynamic signature for this experiment is also displayed in the inset. Most importantly, the A value is 0.064 indicating that this compound is a PPI inhibitor.TA Instruments – Application Note__________________________________________________________________________________ Figure 2. ITC titration of sCD4 into gp120 in the presence of 200µM NBD-556Characterization of PPI InhibitorThe experiments in Figures 1 and 2 identify a compound as a PPI inhibitor. A more complete characterization of the compound is obtained by measuring its binding thermodynamics to the target protein. If the target protein is not known, separate ITC experiments with each of the two proteins need to be performed. The A parameter is related to the affinity of the inhibitor to the target by the following equation:(1)where β is the degree of competitiveness of the inhibitor. If β = 0 the inhibitor is absolutely competitive, i.e. either the inhibitor or the protein is bound but not both. If β = 1 the compound does not affect the binding affinity of the protein. This situation can be observed for allosteric inhibitors of protein signaling in which binding of the inhibitor does not affect the binding of the two proteins. For small molecular weightTA Instruments – Application Note__________________________________________________________________________________ compounds β can assume a value between 0 and 1 (7). This situation is possible because the binding footprint of a small molecule is very small when compared to the entire protein/protein interface which can make it possible for both molecules to bind simultaneously. The presence of the small molecule can be thought off as a mutation that lowers the affinity but not abolishes the binding of the protein for its partner. The parameter β can be calculated from the ITC da ta by rearranging equation 1:(2)where A is obtained for the experiments in Figures 1 and 2 and K I from the ITC titration of the inhibitor into the target protein.Figure 3 shows the ITC titration of NBD-556 into gp120 which is the target protein in this particular example. In this experiment, the reaction cell contained 5 uM gp120 and was titrated with 2 µL injections of a 300 µM NBD-556 in the syringe. This experiment is consistent with an association constant, K I, of 3.3 × 105 M-1 or equivalently a dissociation constant K d,I = 1/K I of 3.0 µM. The binding enthalpy is -20.4 kcal/mol and the entropy contribution to binding is 12.9 kcal/mol. The thermodynamic signature for this inhibitor is also displayed in the inset. Equation 2 indicates that the binding of NBD-556 is characterized by a β value of 0.05 which is characteristic for a moderately competitive inhibitor. The optimization of protein/protein inhibitors requires maximization of the binding affinity and modulation of the degree of competitiveness, β, in order to develop more or less competitive inhibitors according to the specific design needs. The results presented here demonstrate the unique capability of ITC to guide the optimization of protein/protein inhibitors.TA Instruments – Application Note__________________________________________________________________________________ Figure 3. ITC titration of the small molecular weight inhibitor NBD-556 into gp120.ConclusionsThe inhibition of protein/protein interactions is a major frontier in the pharmaceutical and biotechnological industries. The identification and optimization of protein/protein inhibitors require accurate measurements of their binding affinity as well as the efficiency with which they compete with the target protein. ITC is uniquely suited to perform this task as it can provide both the binding affinity and the degree of competitiveness of an inhibitor. Contrary to traditional enzyme inhibitors in which the degree of inhibition is proportional to binding affinity, for protein/protein inhibitors binding affinity is not sufficient. Due to the large size of the protein/protein binding footprint when compared to the size of a ~500 MW molecule, inhibitor optimization also requires tracking of the degree of competitiveness since binding affinity alone does not reflect inhibitor potency. The experiments presented here demonstrate the critical role of the Nano ITC LV in the development of protein/protein interaction inhibitors.TA Instruments – Application Note__________________________________________________________________________________ References1. Wells, J. A., and McClendon, C. L. (2007) Reaching for high-hanging fruit in drugdiscovery at protein-protein interfaces, Nature450, 1001-1009.2. Zinzalla, G., and Thurston, D. E. (2009) Targeting protein-protein interactions fortherapeutic intervention: a challenge for the future, Future Med Chem1, 65-93.3. Dalgleish, A. G., Beverley, P. C., Clapham, P. R., Crawford, D. H., Greaves, M.F., and Weiss, R. A. (1984) The CD4 (T4) antigen is an essential component ofthe receptor for the AIDS retrovirus, Nature312, 763-767.4. Klatzmann, D., Champagne, E., Chamaret, S., Gruest, J., Guetard, D., Hercend,T., Gluckman, J. C., and Montagnier, L. (1984) T-lymphocyte T4 moleculebehaves as the receptor for human retrovirus LAV, Nature312, 767-768.5. Schӧn, A., Madani, N., Klein, J. C., Hubicki, A., Ng, D., Yang, X., Smith, A. B.,3rd, Sodroski, J., and Freire, E. (2006) Thermodynamics of binding of a low-molecular-weight CD4 mimetic to HIV-1 gp120, Biochemistry45, 10973-10980.6. Zhao, Q., Ma, L., Jiang, S., Lu, H., Liu, S., He, Y., Strick, N., Neamati, N., andDebnath, A. K. (2005) Identification of N-phenyl-N'-(2,2,6,6-tetramethyl-piperidin-4-yl)-oxalamides as a new class of HIV-1 entry inhibitors that prevent gp120binding to CD4, Virology339, 213-225.7. Schӧn, A., Lam, S. Y., and Freire, E. (2011) Thermodynamics-based drugdesign: strategies for inhibiting protein-protein interactions, Future Med Chem3, 1129-1137.。

identification医学解释

Identification in MedicineIdentification plays a crucial role in the field of medicine, as it enables healthcare professionals to accurately diagnose and treat patients. In this article, we will explore the various aspects of identification in medicine, including patient identification, disease identification, and identification of medical professionals.Patient IdentificationPatient identification is the process of correctly identifying an individual seeking medical care. It is essential to ensure patient safety, prevent medical errors, and maintain accurate medical records. There are several methods used for patient identification: and Date of Birth: The most common method of patientidentification is by using their full name and date of birth. This information is usually cross-checked with official documents such as passports or identity cards.2.Medical Record Number: Many healthcare facilities assign a uniquemedical record number to each patient. This number serves as areliable identifier throughout the patient’s interactio ns withthe healthcare system.3.Biometric Identification: Some hospitals utilize biometrictechnologies such as fingerprint or iris scanning to identifypatients accurately. These methods provide an extra layer ofsecurity and help eliminate errors due to name similarities.Proper patient identification is critical to avoid misdiagnosis, medication errors, or incorrect treatments. Healthcare providers must follow strict protocols to ensure accurate patient identification at all times.Disease IdentificationIdentification of diseases is another vital aspect of medicine. Accurate diagnosis allows healthcare professionals to provide appropriate treatment and improve patient outcomes. Disease identification involves several steps:1.Medical History: Gathering a detailed medical history from thepatient helps identify potential risk factors or symptomsassociated with specific diseases.2.Physical Examination: A thorough physical examination can revealimportant signs that aid in diagnosing certain diseases.3.Diagnostic Tests: Laboratory tests, imaging studies (such as X-rays or MRIs), and genetic testing can provide valuableinformation for identifying diseases accurately.4.Specialized Consultations: In complex cases, doctors may referpatients to specialists for further evaluation and diagnosis.Advancements in medical technology and research have led to the development of innovative diagnostic tools, such as moleculardiagnostics and telemedicine. These tools enable faster and moreaccurate disease identification, ultimately improving patient care. Identification of Medical ProfessionalsIdentification within the medical profession is essential for ensuring patient safety, maintaining professional standards, and regulating healthcare providers. Here are some key aspects of medical professional identification:1.Licensing: Medical professionals must obtain a license from theappropriate regulatory body in their country or region. Thislicense confirms their qualifications and authorizes them topractice medicine.2.Credentials: Healthcare providers often display their credentials,such as degrees, certifications, or specializations, to establishtheir expertise in specific areas.3.Identification Badges: Medical professionals typically wearidentification badges that include their name, photograph, andprofessional designation. This allows patients to easily identifytheir caregivers and enhances trust.4.Online Verification: Many countries have online platforms wherepatients can verify the credentials and licensing status ofhealthcare providers before seeking treatment.Strict regulations and oversight ensure that only qualified individuals can practice medicine. Identification measures help maintain theintegrity of the medical profession and protect patients fromunqualified practitioners.ConclusionIdentification plays a vital role in medicine by ensuring accuratepatient care, disease diagnosis, and regulation of healthcare professionals. Patient identification methods like using names, biometrics, or unique identifiers help prevent errors and enhance safety. Accurate disease identification through medical history, physical examination, diagnostic tests, and specialized consultations ensures appropriate treatment. The identification of medical professionals through licensing processes, credentials display, identification badges, and online verification helps maintain professional standards.By prioritizing proper identification practices in medicine, we can improve patient outcomes, reduce errors, enhance patient safety, and maintain the integrity of the healthcare system as a whole.Note: This article provides general information about identification in medicine but does not constitute medical advice. Always consult a healthcare professional for personalized medical guidance.。

美国专利术语及含义

美国专利术语Assignee专利权受让人：在专利的领域内，专利权受让人指的是专利所有权人。

专利权受让人可做是否出让或转售专利等决定。

Best Mode最佳实施例：最佳实施例是发明人在申请专利当时，认为可以实施发明最好的方式，美国专利法中要求说明书中必须要记载最佳实施例。

Certificate of Correction订正书：订正书是美国专利局用来订正专利中拼字或打字错误的文件。

Continuation Application延续案：延续案为较早的申请案（称为母案）还在审查期间所提出的申请，并使用母案申请日来作为优先权日，可以说是母案的延续。

通常提出延续案的目的是为了申请不同于母案的请求项范围。

Continuation-in-part (CIP) Application部分延续案：部分延续案为较早的申请案（称为母案）还在审查期间所提出的申请。

通常提出部分延续案的目的是为了加入母案没有揭露的特征以及申请不同于母案的请求项范围。

其中，沿用母案的特征部分可主张母案的优先权日。

Continued Prosecution Application (CPA)延续审查案：延续审查案通常会在申请人收到最终核驳后的六个月内提出。

通常提出延续审查案的目的是为了延续审查。

另外，延续审查案并不能用在2000年5月29日起申请的「发明专利申请案」或是「植物专利申请案」，新式样专利并没有在此限。

Claim请求项或称权利项：请求项是用来定义专利的保护范围的部分。

Defensive Patent防御专利：有的人申请专利的目的并不在于主动攻击竞争对手，而是希望将来被控告专利侵权时，可以利用这些专利保护自己并予以反击。

在这种状况下，竞争对手在考虑控告侵权前，由于害怕将来被对方以这些专利反控侵权，常会因而打消控告的念头。

这样的专利由于具有防御的功能，因此称为防御专利。

Declaration声明书：声明书是申请美国专利时需缴交的文件，发明人必须在文件中声明自己为真正的发明人、声明已阅读和了解说明书内容，以及会向专利局揭露任何与申请案专利性有关的技术资料。

System Identification and Control

System Identification and Control System identification and control are essential components in the field of engineering, playing a crucial role in various applications such as robotics, aerospace, automotive, and industrial automation. The process of system identification involves modeling and analyzing the behavior of a system based on input-output data, while control involves designing and implementing strategies to regulate and manipulate the system's behavior. These two concepts are closely intertwined, as accurate system identification is necessary for effective control design and implementation. One of the key challenges in system identification is the accurate and reliable modeling of complex and nonlinear systems. Real-world systems often exhibit nonlinear behavior, making it challenging to develop accurate mathematical models that can capture their dynamics. This is particularly true in the case of biological systems, such as the human body, where the underlying dynamics are highly complex and not fully understood. As a result, engineers and researchers face the daunting task of developing models that can accurately represent the behavior of such systems, which is essential for designing effective control strategies. Another challenge in systemidentification and control is the presence of uncertainties and disturbances in the system. External factors such as environmental changes, sensor noise, and measurement errors can introduce uncertainties and disturbances that affect the system's behavior. These uncertainties can significantly impact the accuracy of the system identification process and the performance of control strategies. As a result, engineers need to develop robust and adaptive control algorithms that can effectively handle these uncertainties and disturbances to ensure the stability and performance of the system. Moreover, the implementation of system identification and control strategies often requires a deep understanding of the underlying physics and dynamics of the system. This necessitates interdisciplinary collaboration between engineers, mathematicians, physicists, and domain experts to develop accurate models and control strategies. Furthermore, the integration of advanced technologies such as machine learning and artificial intelligence has the potential to revolutionize system identification and control by enabling the development of data-driven models and adaptive control algorithms. From apractical standpoint, the successful implementation of system identification and control strategies can have a profound impact on various industrial and technological applications. For example, in the field of robotics, accurate system identification is crucial for developing models that can accurately represent the dynamics of robotic systems, enabling precise control and manipulation of the robot's behavior. Similarly, in the automotive industry, system identification and control play a critical role in the development of autonomous vehicles, where accurate modeling and control strategies are essential for ensuring the safety and reliability of the vehicle's operation. In conclusion, system identification and control are fundamental concepts in the field of engineering, with wide-ranging applications in various industries. While there are numerous challenges associated with accurate system identification and robust control design, the potential benefits of successful implementation are substantial. As technology continues to advance, the integration of advanced techniques such as machine learning and artificial intelligence has the potential to revolutionize the field, enabling the development of more accurate models and adaptive control strategies. Ultimately, the successful implementation of system identification and control strategies has the potential to drive innovation and progress in numerous industrial and technological applications.。

Testing and modeling multivariate threshold models

i=1
q
( )
i
j
xt?i +
( )
t
j
if rj? < zt?d
1
rj
(2)
where j = 1; ; s, cj are constant vectors, and p and q are non-negative integers. The innovations satisfy tj = j = at, where j = are symmetric positive de nite matrices and fat g is a sequence of serially uncorrelated random vectors with mean zero and covariance matrix I , the identity matrix. The threshold variable zt is assumed to be stationary and have a continuous distribution. Model (2) has s regimes and is a piecewise linear model in the threshold space zt?d , but it is nonlinear in time when s > 1. For model (2), we assume that the threshold variable zt is known, but the delay d, the number of regimes s, and the thresholds ri are unknown. Our goal is two-fold. First, we propose a test statistic to detect the need of employing such a model against the alternative of a linear model, i.e. s = 1 versus s > 1. The proposed test is a generalization of that in Tsay (1989) for the univariate case and has an asymptotic chi-square distribution. The test is simple, performs well in nite samples, yet it does not depend on the alternative model or encounter the problem of unde ned parameters under the null hypothesis. The generalization also allows for exogenous variables and conditional heteroscedasticity. Second, we consider a procedure for building such a multivariate threshold model including estimation of d and the thresholds. We employ the conditional least squares method in estimation and Akaike information criterion in model selection. The procedure is easier to apply than that of Tsay (1989) who uses scatterplots that often require subjective interpretations. The paper is organized as follows. In Section 2, we consider an arranged regression analysis that transforms the threshold model in (2) into a change-point problem. We then use recursive least squares to obtain predictive residuals in the arranged regression and use the standardized predictive residual to construct the proposed test statistic. The asymptotic distribution of the proposed test is derived. We also use simulation to study the nite-sample performance of the proposed test. Some related literature is also reviewed. In Section 3, we brie y address conditional least squares estimation of the model. In Section 4, we propose a procedure for model building. Akaike information criterion is used to select the thresholds as well as other parameters. The proposed test and modeling procedure are applied in Section 5 to two real examples of high-frequency data in nance. We compare the results with those available in the literature using other methods. The model we built appears to be in closer agreement with common expectations. Finally, we apply the modeling procedure to U.S. monthly interest rates and two daily river ow series of Iceland.

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Identiﬁcation of Nonlinear Systems With Unknown Time Delay Based on Time-Delay Neural NetworksX.M.Ren and A.B.RadAbstract—In this letter,we address the problem of online identiﬁcation of nonlinear continuous-time systems with unknown time delay based on neural networks(NNs).A novel time-delay NN model with learning al-gorithm is employed to perform simultaneous system identiﬁcation and time-delay estimation.The proposed network is an extended version of the time-delay-free dynamical NN.Rigorous stability proof for the identiﬁca-tion error is given by means of Lyapunov theory.The simulation studies are provided to demonstrate the performance of the identiﬁcation algorithm and clarify the theoretical implications.Index Terms—Neural networks(NNs),system identiﬁcation,systems with unknown time delay.I.I NTRODUCTIONMany systems exhibit a time delay when information,material,or energy is transferred to or from them.It is well known that the presence of time delay leads to difﬁculties in a closed-loop control system such as sluggish response,detuned control,and instability.The time delay appears nonlinearly in the mathematical formulation of the system that complicates the online identiﬁcation if the delay is not known precisely. Online identiﬁcation of such systems has turned out to be a central problem in adaptive control.Neural networks(NNs)are effective tools for system identiﬁcation due to their universal approximation abilities,learning and adaptation abilities[1],[2].The most widely used NNs are the feedforward and recurrent NNs.Despite the immense popularity of the feedforward NNs for approximation of nonlinear functions,these networks share some drawbacks including susceptibility to external noise and difﬁ-culty of obtaining an independent system simulator[3],[4].Various recurrent networks have been offered to remedy the limitations of the feedforward networks[5]–[7].Recently,some researchers have de-veloped learning algorithms for NNs based on the Lyapunov stability theory[8]–[15].A survey of the current work on NNs for identiﬁcation and control of dynamical systems appears in[16].It should be noted that almost all the existing neural identiﬁcation strategies are suitable for nonlinear systems free from time delay or with known time delay. There are not many results on the adaptive control of continuous-time nonlinear systems with unknown time delay.To the best of our knowledge,the identiﬁcation of nonlinear systems with unknown time delay and in particular time delay estimation have not been discussed in the NN literature.The main contribution of this letter is to present a new time-delay NN for the identiﬁcation of multiple-input–multiple-output (MIMO)continuous-time high-order nonlinear systems with unknown time delay.The proposed NN is an extension of the time-delay-free dynamical NN.The unknown time delay is treated as a special param-eter in the proposed NN.The time-delay NN identiﬁcation model with learning algorithms is developed for simultaneous estimation of time Manuscript received July10,2006;revised February21,2007;accepted Feb-ruary26,2007.This work was supported by The Hong Kong Polytechnic Uni-versity under Grant A.G-U20and the National Natural Science Foundation of China under Grant60474033.X.M.Ren is with the Department of Automatic Control,Beijing Institute of Technology,Beijing100081,China(e-mail:xmren@).A.B.Rad is with the Faculty of Engineering and Industrial Sciences, Swinburne University of Technology,Hawthorn,3122Vic.,Australia(e-mail: arad@.au).Digital Object Identiﬁer10.1109/TNN.2007.899702delay and the dynamical system.In addition,the stability of the iden-tiﬁcation error is analyzed by Lyapunov theory.Simulation results are included to demonstrate the performance of the proposed method.II.P ROBLEM S TATEMENTLet D be an open set of R n+111+n+pq,and K be a compact subset of D.We consider a class of nonlinear systems described asy(n)1=f1(y1;_y1;...;y(n01)1;...;y m;_y m;...;y(n01)m;u(t0 3);_u(t0 3);...;u(p01)(t0 3))...y(n)m=f m(y1;_y1;...;y(n01)1;...;y m;_y m;...;y(n01)m;u(t0 3);_u(t0 3);...;u(p01)(t0 3))(1)where u2R q and y=[y1;...;y m]T2R m are the control and system output,respectively.The mappings f i:R n+111+n+pq!R; i=1;...;m,are the unknown continuous functions and 3is the unknown time delay.The identiﬁcation objective is that given an input u,design an appropriate NN model with learning algorithm such that the output of the NN approximates the plant output with an acceptable accuracy for the same input while estimating the unknown time delay.Assumption1:For a bounded input u(t);t2[0;T],where T is an arbitrary positive constant,the plant(1)has a unique solution and generates a vector[y1;_y1;...;y(n01)1;...;y m;_y m;...;y(n01)m;u(t0 3);_u(t0 3);...;u(p01)(t0 3)]T2K:Deﬁnition1[17]:Consider the signals x:[0;1)!R n;z: [0;1)!R+and the setS(z)=x:[0;1)!R n jt+Ttx T( )x( )dt+Ttz( )d +C(2) for someC0and8t;T0.We say that x is z-small in the mean if x2S(z).III.T IME-D ELAY NN I DENTIFICATION M ODELIn this section,we develop a time-delay NN model based on the input–output data that is computationally effective for the identiﬁcation of nonlinear system(1)and the time-delay estimation.The plant(1)can be rewrittenasy(n)1...y(n)m=ni=11i y(n0i)1...ni=1mi y(n0i)m+F1( y; u(t0 3))...F m( y; u(t0 3))(3)where y=[y1;_y1;...;y(n01)1;...;y m;_y m;...;y(n01)m]T, u(t0 3)=[u(t0 3);_u(t0 3);...;u(p01)(t0 3)]T,F j( y; u(t0 3))= ni=1ji y(n0i)j+f j( y; u(t0 3)),j=1;...;m,and ji are ap-propriate constants to be chosen such that all roots of s n+ j1s n01+ 111+ jn=0are in the open left half-plane.Denote H(s)= diag(h1(s);...;h j(s);...;h m(s));h j(s)=s n+n i=1 ji s n0i. From(3),we obtainH(s)y=F( y; u(t0 3))(4) where F( y; u(t0 3))=[F1( y; u(t0 3));...;F m( y; u(t0 3))]T. We consider a time-delay NN for identiﬁcationH(s)^y=w T8( y; u(t0 ))(5)1045-9227/$25.00©2007IEEEwhere ^y is the network output, is the estimated time delay,w 2R L 2mis the weight matrix,and 8(y ; u (t 0 ))2R L is the basis function with input delay.Remark 1:When the time delay is zero,the time-delay NN model (5)can be described byH (s )^y =w T 8( y ; u (t )):(6)Let us de ﬁne h j (s )=(s +k d j ) j (s )(k d j >0)and the new statevector x = (s )^y with (s )=diag( 1(s );...; j (s );... m (s ));then,the dynamic NN (6)can be transformed into the form as_x =K d x +w T8( y ; u (t ))(7)where K d =0diag(k d 1;...;k d j ;...;k dm ).This network model is similar to the dynamic networks proposed by many authors,for ex-ample,[6],[7],[10],and [18].Remark 2:We refer to the function 8( y ; u (t 0 ))as the basis func-tion with input delay.If the time delay is equal to zero,w T 8( y ; u (t ))corresponds to the general linearly parameterized approximator.Sev-eral network basis functions such as radial basis function (RBF)NNs [19],high-order NNs [10],[20],or fuzzy systems [21]can be applied for identi ﬁcation purpose.It should be noted that the high-order net-work basis function is employed in this letter since the usage of the higher order connections in NNs dramatically improves their storage capacity [10],[20].The higher is the number of high-order connec-tions,the less is the approximation error.In addition,the high-order NN is able to simulate higher order nonlinear data and consequently provides superior simulation results compared with other NNs [22].Despite the fact that NNs are very powerful in learning nonlinear dy-namics,approximation error always exists no matter how the parame-ters of the NN are adjusted.Without loss of generality,the system (4)can be described byH (s )y =w 3T 8( y ; u (t 0 3))+"f(8)over the compact set K ,where w 3is the optimal weight matrix, 3isthe actual value of time delay ,and "f is the NN approximation error.Assumption 2:The NN approximation error is bounded by a positiveconstant ^"over the compact set K ,i.e.,j "fj ^".Let us de ﬁne the identi ﬁcation error as e =y 0^y.From (5)and (8),the identi ﬁcation error is obtained by H (s )e = w T8( y ; u (t 0 ))+w 3T [8(y ; u (t 0 3))08( y ; u (t 0 ))]+"f (9)where the weight estimation error w =w 30w .By using the ﬁrst-order Taylor series expansion,we obtain w 3T [8( y ; u (t 0 3))08( y ; u (t 0 ))]= w 3T 8 (y ; u (t 0 ))+O (j j )(10)where = 30 ;O (j j )represents the high-order term of the Taylorseries expansion,and 8 ( y ; u (t 0 ))is the derivative of 8( y ; u (t 0 ))with respect to .By (9)and (10),we haveH (s )e = w T 8( y ; u (t 0 ))+ w T 8 ( y ; u (t 0 ))+d(11)where d = w T 8 ( y ; u (t 0 ))+"f +O (j j ).According to (11),the ﬁltered error equation can be written ase i = w T i ~8i ( y ; u (t 0 ))+ w T i ~8 i (y ; u (t 0 ))+~d i ;i =1;...;m (12)where ~8i ( y ; u (t 0 ))=8( y ; u (t 0 ))=h i (s );~d i =d i =h i (s );~8 i ( y ; u (t 0 ))=8 ( y ; u (t 0 ))=h i (s ); w T i ;w T iand d i are the i th lines of w T ;w T and d ,respectively.De ﬁnethe normalized identi ﬁcation error e i =e i =(1+ i Tii ),wherei 0and i =[~8T i ( y ; u (t 0 ));w T i ~8 i ( y ; u (t 0 ))]T .Denote i ; as constraint sets for w i ; ,respectively,that is, i =f w i :k w ik M i ;M i >0g ; =f :jj M ;M >0g .The gradient algorithm with projection for w i is chosen as in [23],i.e.,as shown in (13)at the bottom of the page,where i >0is a gain matrix referred to as the learning rate.Since time delay is a special parameter,we use the following law to ensure its estimate value greater than zero.Whenever any =c ,where c >0is a small constant,we use (14),shown at the bottom of the page,where >0.Otherwise,we use (15),shown at the bottom of the page.Remark 3:The projection algorithm described by (13)and (15)guarantees that k w ikM i and jj M for the initial conditions satisfying k w i (0)k M i ;j (0)j M .Please see [23]for the proof.In addition,by (14),we can see that if =c ,then _0is true.There-fore,cM is true.Theorem:Consider the plant (1)with the time-delay NN identi ﬁca-tion model (5)whose parameters are adjusted by (13)–(15);then,the following properties hold:1) e i ;w i ; ;_w i ;_ 2L 1;2) e i ;_w i ;_ 2S(m i =1~d 2i =(1+ i T i i )).Proof:1)From (12),we have e i =w Ti~8i ( y ; u (t 0 ))1+ i T i i + w T i ~8 i (y ; u (t 0 ))1+ i T i i +~d i 1+ i Ti i:(16)As in the Remark 3,we can establish that the adaptivelaws guarantee that the parameters w i ; are bounded.Since~8i ( y ; u (t 0 ))=(1+ i T i i )2L 1;~d i =(1+ i T i i )2L 1and w T i ~8 i ( y ; u (t 0 ))=(1+ i Ti i )2L 1,we can concludethat ei ; e i 1+ i Ti i 2L 1.Furthermore,from (13),(15),_w i=i ~8i ( y ; u (t 0 )) e i ;if k w i k <M i or k w i k =M iand w T i ~8i ( y ; u (t 0 )) eii ~8i ( y ; u (t 0 )) e i 0iw i w T i ~8i (y ; u (t 0 )) e ik w i k 2;ifk w i k =M iandw T i ~8i (y ; u (t 0 )) e i >0(13)_=m i =1w T i ~8 i (y ; u (t 0 )) e i ;if m i =1w T i ~8 i ( y ; u (t 0 )) e i >00;ifm i =1w T i ~8 i ( y ; u (t 0 )) ei 0(14)_=m i =1w T i ~8 i (y ; u (t 0 )) e i ;if j j <M or j j =M andm i =1w T i ~8 i (y ; u (t 0 )) ei 00;ifj j =Mandm i =1w T i ~8 i ( y ; u (t 0 )) e i >0(15)and the fact that the orthogonal projection always decreases the norm of a vector,we obtaink _w ik k i k 1 e i1+ i Ti i 1k ~8i ( y ; u (t 0 ))k1+ i Ti i(17)j _ jmi =1e i1+ i Ti i 1w T i ~8 i (y ; u (t 0 ))1+i Ti i(18)which implies that _w i ;_2L 1.2)Let us consider a Lyapunov-like functionV =12m i =1w T i 01i wi + 22:(19)The time derivative of V along the solutions of (13)–(15)is_V=0mi =1w T i ~8i ( y ; u (t 0 )) e i +I 1mi =1w T i ~8i (y ; u (t 0 ))e i k w i k w T i w i0I 2mi =1w T i ~8 i (y ;u (t 0 )) e i ++0I 3mi =1w T i ~8 i (y ; u (t 0 )) e i cc (20)where I 1;I 2;I 3are de ﬁned as I 1=0(or 1);I 2=1(or 0);I 3=1(or 0)if the ﬁrst (or second)lines of (13),(15),and (14)are true,respectively; +is the collection of >c , c =c; += 30 +; c = 30 c ;and [w T i ~8 i (y ; u (t 0 )) e i ]+(or [w T i ~8 i ( y ; u (t 0 )) e i ]c )denotes the collection of the corre-sponding elements of w T i ~8 i ( y ; u (t 0 )) e i with respect to +(or c ).By applying the projection algorithm property [23],we have the term with I 1in (20)being nonpositive.If I 3=0,from(14),one obtains thatc = 30 c = 30c 0and m i =1[w T i ~8 i(y ; u (t 0 )) e i ]c c 0,which implies that0I 3mi =1w T i ~8 i(y; u (t 0 )) e i cc 0mi =1w T i ~8 i (y ; u (t 0 ))e i cc :(21)Similarly,we can prove that0I 2mi =1w T i ~8i (y ;u (t 0 )) e i++mi =1w T i ~8 i (y ; u (t 0)) ei ++:(22)Therefore,we have _Vm i =10 w T i ~8i ( y ; u (t 0 )) e i 0 wT i ~8 i (y ; u (t)) e i :(23)Substituting theerror (12)into (23),we obtain_Vmi =10 e 2i 1+ iT ii + e i~di 12mi =10 e 2i 1+ i T ii +~d2i 1+ iTi i:(24)Integrating both sidesof (24),it follows that:mi =1t +Tte 2i1+ i Ti i dt +T tmi =1~d2i 1+ i Ti id +2(V (t )0V (t +T )):(25)Since V is bounded due to w i ; 2L 1,it follows thate i 1+ i T i i 2S (m i =1~d 2i =(1+ i T i i )),which implies thate i ; e i T i i 2S (m i =1~d 2i =(1+ i T i i )).From (17)and (18),wecan prove that _w i ;_ 2S (m i =1~d 2i =(1+ i T i i ))due to ~8i (y ; u (t 0 ))=(1+ i T i i )2L 1;w T i ~8 i ( y ; u (t 0 ))=(1+ i Ti i )2L 1.Remark 4:This theorem explicitly states that the adaptive laws (13)–(15)guarantee that e i ;w i ; ;_w i ,and _ are bounded for alli =1;...;m .In the special case that ~d i =0,we can obtain thate i ;_w i ,and _ converge to zero asymptotically.This can be estab-lished by using similar arguments as in [17].In order to achieve the convergence of the parameters to their correct values,the additional assumption of persistence of excitation (PE)needs to be imposed on the regressive vector i .In this case,the parameter convergence property can be discussed along the same lines as the proof of Theorem8.5.6(iv)in [23],that is,if Tii ; i 2L 1and i is PE with level 0>0that is independent of ~d i ,then i =[ w T i ;]T convergesexponentially to the residual set D =fjk kc 1(f 0+d )g ;where d =sup t m i =1j ~d i j =1+ i T i i ;c 1is a constant andf 0is a designconstant.Remark 5:The adaptive law (15)for the time delay has a local be-havior,that is,it requires that the initial estimate of the parameter should be near the actual value.Pintelon and Schoukens [24]suggested that a “suf ﬁciently near ”starting value for the delay is necessary to avoid the local minima.Remark 6:If the time delay is zero,the time-delay NN (5)cor-responds to the time-delay-free NN model.The same stability prop-erty holds for the identi ﬁcation of time-delay-free nonlinear systems (1).The update laws given by (13)–(15)are based on the projection al-gorithm that can ensure the boundedness of the parameters during the learning process.The other robust adaptive algorithms,such as -mod-i ﬁcation,deadzone [23]commonly used in adaptive control,can also be employed to guarantee bounded parameter estimates.Remark 7:Consider a single-input –single-output (SISO)linear time-invariant plant with time delay described byy (n )+a 31y (n 01)+111+a 3n y =b 30u(m )(t 0 3)+b 31u (m 01)(t 0 3)+111+b 3m u (t 0 3):(26)Let a 1;...;a n ;b 0;b 1;...;b m ;and be the estimates ofa 31;...;a 3n ;b 30;b 31;...;b 3m ;and 3,respectively.Since the plant (26)is alinear system,we use the time-delay NN of the form^y (n )=0ni =1i ^y (n 0i )+w T 8( y ; u (t 0 ))(27)as the identi ﬁcation model,where y=[y;_y;...;y (n 01)]T ;w =[ 10a 1;...; n 0a n ;b 0;...;b m ]T ; u(t 0 )=[u (t 0 );_u (t 0 );...;u(m 01)(t 0 )]T;and 8( y ; u (t 0 ))=[y (n 01);...;y;u (m )(t 0 );...;u (t 0 )]T .The characteristic of the network model (27)is that the learning of the weights corresponds to the estimation of unknown parameters of the system (26).Therefore,the time-delay identi ﬁcation model (27)can be used to simultaneously estimate time delay and rational dynamics of linear time-invariant systems.Fig.1.Output responses for the time-delay NN identi ﬁcation (solid line:y ;dotted line:^y).Fig.2.Output velocities for the time-delay NN identi ﬁcation (solid line:_y ;dotted line:_^y).Fig.3.Estimated time delay.IV .S IMULATIONTo show the feasibility and effectiveness of the time-delay NN iden-ti ﬁcation scheme,we consider a nonlinear system with time delay given by _y 1=y 2_y 2=0y 21+0:1y 2209:8cos(y 1)+(100:2sin 2(y 1))u (t 04)y =y 1(28)or,equivalently,of the form y =0_y 1+0:1_y 09:8cos(y )+(100:2sin 2(y ))u (t 04)(29)where 3=4is the known time delay.Since the plant is a second-order nonlinear system,we use the time-delay NN shown in (5)as theidenti ﬁcation model,that is^y =0 1_^y 0 2^y +w T 8(y;_y;u (t 0 ))(30)Fig.4.Output responses for the NN identi ﬁcation without input delay (solid line:y ;dotted line:^y).Fig.5.Output velocities for the NN identi ﬁcation without input delay (solid line:_y ;dotted line:_^y ).where 8(y;_y;u (t 0 ))=[ (y ); (_y ); (y ) (_y ); (_y 2); (y )u (t 0 ); (_y )u (t 0 )]T and w =[w 1;w 2;w 3;w 4;w 5;w 6]T .The design parameters are speci ﬁed as follows.The sigmoid function is chosen as (z )=2=(1+e 0z=2)00:5.The input signal is a square wave with amplitude of 2.5and a period of 12.The integration time step used for the simulations is 0.01s.The initial parameters for the NN are selected to be (0)=2and w i (0)=0:5;i =1;...;6.Let1=5; 2=6:25;y (0)=0;_y (0)=0;_^y (0)=0;^y (0)=0.The learning rates for the weight w and time delay are selected as =diag(200;200;50;55;65;60)and =4:25,respectively.The following simulation results show the identi ﬁcation ability of the time-delay NN.Figs.1and 2show the output responses and output velocity tracking trajectories for the plant (29)and the network model (30),re-spectively.Fig.3shows the estimated parameter when the update laws described by (13)–(15)are used.It is shown that the time-delay NN exhibits satisfactory performance in the identi ﬁcation of the non-linear systems with unknown time delay.In addition,the estimated time delay can converge to its corresponding correct value.To show the ef-fect of time delay on identi ﬁcation performance,the simulation is re-done for the NN model (30)without input delay.Figs.4and 5show the corresponding results with the same parameters except that the learning rate is appropriately chosen as =diag(150;150;80;5;5;6).If wede ﬁne the relative identi ﬁcation error as E=(y 0^y)dt=ydt;E 1corresponding to Figs.1and 4is 0.0774and 0.0991,respectively,and E 2corresponding to Figs.2and 5is 00:0011and 00:1515,respec-tively.It can be seen that the time-delay NN gives a better approxima-tion accuracy to the original plant due to the time-delay estimation.V .C ONCLUSIONThis letter investigates the time-delay NN for the identi ﬁcation of nonlinear systems with unknown time delay.The characteristic of the proposed NN is its ability for online identi ﬁcation of dynamical nonlinear systems and the estimation of time delay.Rigorous stability analysis is performed based on Lyapunov method.Simulation results demonstrate the effectiveness of the proposed identi ﬁcation scheme.R EFERENCES[1]G.Cybenko,“Approximations by superpositions of a sigmoidal func-tion,”Math.Control,Signals,Syst.,vol.2,pp.183–192,1989.[2]K.Funahashi,“On the approximate realization of continuous map-pings by neural networks,”IEEE Trans.Neural Netw.,vol.2,no.1,pp.183–192,Jan.1989.[3]K.J.Hunt,D.Sbarbaro,R.Zbikowski,and P.J.Gawthrop,“Neuralnetworks for control systems —A survey,”Automatica ,vol.28,pp.1083–1112,1992.[4]D.T.Pham and X.Liu,“Dynamic system identi ﬁcation using partiallyrecurrent neural networks,”J.Syst.Eng.,vol.2,no.2,pp.90–97,1992.[5]T.W.S.Chow,X.D.Li,and Y.Fang,“A real-time learning controlapproach for nonlinear continuous-time system using recurrent neural networks,”IEEE Trans.Ind.Electron.,vol.47,no.2,pp.478–486,Apr.2000.[6]A.S.Poznyak,W.Yu,E.N.Sanchez,and J.P.Perez,“Nonlinear adap-tive trajectory tracking using dynamic neural networks,”IEEE Trans.Neural Netw.,vol.10,no.6,pp.1402–1411,Nov.1999.[7]G.A.Rovithakis,“Tracking control of multi-input afﬁne nonlinear dy-namical systems with unknown nonlinearities using dynamical neural networks,”IEEE Trans.Syst.Man,Cybern.B,Cybern.,vol.29,no.2, pp.179–189,Apr.1999.[8]S.S.Ge and C.Wang,“Adaptive neural control of uncertain MIMOnonlinear systems,”IEEE Trans.Neural Netw.,vol.15,no.3,pp.674–692,May2004.[9]J.Q.Huang and F.L.Lewis,“Neural-network predictive control fornonlinear dynamic systems with time delay,”IEEE Trans.Neural Netw.,vol.14,no.2,pp.377–389,Mar.2003.[10]E.B.Kosmatopoulos,M.M.Polycarpou,M.A.Christodoulou,andP.A.Ioannou,“High-order neural network structures for identiﬁcation of dynamical systems,”IEEE Trans.Neural Netw.,vol.6,no.2,pp.422–431,Mar.1995.[11]M.M.Polycapou and M.J.Mears,“Stable adaptive tracking of uncer-tain systems using nonlinearly parameterized on-line approximator,”Int.J.Control,vol.70,no.3,pp.363–384,1998.[12]X.M.Ren,A.B.Rad,P.T.Chan,and W.L.Lo,“Identiﬁcation andcontrol of continuous-time nonlinear systems via dynamic neural net-works,”IEEE Trans.Ind.Electron.,vol.50,no.3,pp.478–486,Jun.2003.[13]D.Wang and J.Wang,“Neural network-based adaptive dynamic sur-face control for a class of uncertain nonlinear systems in strict-feed-back form,”IEEE Trans.Neural Netw.,vol.16,no.1,pp.195–202, Jan.2005.[14]C.F.Hsu,C.M.Lin,and T.T.Lee,“Wavelet adaptive backsteppingcontrol for a class of nonlinear systems,”IEEE Trans.Neural Netw., vol.17,no.5,pp.1175–1183,Sep.2006.[15]Z.Man,H.R.Wu,S.Liu,and X.Yu,“A new adaptive backpropaga-tion algorithm based on Lyapunov stability theory for neural networks,”IEEE Trans.Neural Netw.,vol.17,no.6,pp.1580–1590,Nov.2006.[16]Automatica(Special Issue on Neural Network Feedback Control),vol.37,Aug.2001.[17]A.Datta and J.Ochoa,“Adaptive internal model control:Design andstability analysis,”Automatica,vol.32,no.2,pp.261–266,1996. 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[23]P.A.Ioannou and J.Sun,Robust Adaptive Control.Upper SaddleRiver,N.J.:Prentice-Hall,1996.[24]R.Pintelon and J.Schoukens,System Identiﬁcation:A Frequency Do-main.Piscataway,NJ:IEEE Press,2001.Working Set Selection Using Functional Gain for LS-SVM Liefeng Bo,Licheng Jiao,and Ling WangAbstract—The efﬁciency of sequential minimal optimization(SMO)de-pends strongly on the working set selection.This letter shows how the im-provement of SMO in each iteration,named the functional gain(FG),is used to select the working set for least squares support vector machine(LS-SVM).We prove the convergence of the proposed method and give some theoretical support for its performance.Empirical comparisons demon-strate that our method is superior to the maximum violating pair(MVP) working set selection.Index Terms—Fast algorithm,least squares support vector machine(LS-SVM),sequential minimal optimization(SMO).I.I NTRODUCTIONSupport vector machines(SVMs)[1]are powerful tools for classiﬁ-cation and regression.Least squares support vector machine(LS-SVM) [2]is a variant of SVMs which replaces the hinge loss function with the squared loss function.When no bias term is used in the LS-SVM formulation,similar expressions are obtained as with kernel ridge re-gression[3]and Gaussian processes regression[4].LS-SVM is formulated as convex quadratic programming with equality constraint;hence,its solution is obtained by solving a set of linear equations.Although this problem is,in principle,solvable,in practice it is intractable for a large data set by the classical techniques, e.g.,Gaussian elimination,because their computational complexity usually scales cubically with the size of training samples.To make LS-SVM applicable to large scale problems,Suykens et al.[5] presented a conjugate gradient(CG)algorithm.Chu et al.[6]gave an improved conjugate gradient algorithm.Keerthi and Shevade[7] proposed a sequential minimal optimization(SMO)algorithm where the maximum violating pair(MVP)is selected as the working set. Jiao et al.[8]developed a fast sparse approximation algorithm for LS-SVM.Empirical comparisons[6],[7]have shown that SMO is more efﬁcient than CG and improved CG for the large scale data sets. Inspired by[9]and[10],we present an improved working set se-lection using functional gain(FG)for LS-SVM.It selects the variable pair leading to a great functional gain as the working set.Although the working set selection using functional gain isﬁrst proposed for SVMs,intuitively,it is more natural for LS-SVM since it does not suffer from the boundary effects caused by inequality constraints ensuring the sparsity in SVMs.We prove that it achieves a greater or equal func-tional gain than the MVP method.Experiments show that the proposed method signiﬁcantly reduces the training time of LS-SVM for large C values.II.W ORKING S ET S ELECTION U SING FGConsider a classiﬁcation or regression problem with training samples f x i;y i g`i=1where x i is the input sample and y i is the corresponding target.Note that the variables in bold face denote the vector.In the Manuscript received November11,2006;revised February12,2007;ac-cepted February17,2007.This work was supported by the National Natural Science Foundation of China under Grant60372050and the National Defense Preresearch Foundation of China under Grant A1420060172.The authors are with the Institute of Intelligent Information Processing,Xi-dian University,Xi’an710071,China(e-mail:blf0218@).Digital Object Identiﬁer10.1109/TNN.2007.8997151045-9227/$25.00©2007IEEE。