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1.检测限和定量限的确定方法

1.检测限和定量限的确定方法

目前的一些常用方法的缺陷
空白
真实
SD
低值
假设
导致低
LOD/Q
无法 区分
虚假
分布
对称
忽略事 实(LOD)
LOB
LOB
空白样本结果接近零时的分布
仪器内部产生该类型的信号时,许多仪器自动转换阴性值信号为零或一个 低值阳性值。因此只提供非阴性浓度值输出 假设该值超过空白测量中实际空白样本显著变异分布的第95百分位数 如果样本产生一个超过该限值的观测值,它可以宣称分析物含量大于零
α=β=5%。一个α值为5%对应使用空白值分布第95百分位数,宣称测量值显著高于空白限值 一个空白值呈Gaussian分布:LoB=µB+1.645σB
LOB
计算方法
•浓度低于零的情况下不被报告或空白值不呈Gaussian分布时(空白值呈不 对称分布),第95百分位数通过其他方法估计 直截了当的程序使用基于命令值的非参数原理。通过大量的Nb值排序,第 95百分位数作为阳性第Nb(95/100+0.5)位观测值来估计
LOB
LOB验证举例
•用户进行25次空白测量(5个样本5天测量5次) 目测检查显示空白值呈不对称分布,因此,非参数估计LoB,在观测区的第 24位和第25位之间线性内插法得LoB=19.17 U/L(=18.01+0.25*(22.6518.01))
LOD
LOD
第II类错误
为了表述第II类错误,一方面不得不考虑最小样本浓度等于LoD,即提供规定概率下超过LoB 的结果 当第II类错误β水平设为5%时,那么95%的测量结果超过LoB
LOD
图示
LOD
样本分布
•如果样本中分析物的实际浓度等于LoB,50%的测量值超过LoB(a)。样本 实际浓度等于LoD,(100%-β)(95%)的样本测量值超过LoB(b) •样本不呈Gaussian分布(且不能转换为Gaussian分布),有可能使用非参 数估计LoD,另外,有必要生产浓度接近暂定LoD的样本。用于检查5%或更 低的测量观测值低于LoB的最低水平

甘薯蛋白抗癌作用研究进展

甘薯蛋白抗癌作用研究进展

荧光显微镜观察细胞凋亡( Hoechst 33258 核染色):将细胞接种到24孔板 上(1.2x105/孔),托血清16-24 h后用不同浓度SPP处理细胞48 h ,吸去培养基,用PBS洗细胞3 次。然后用2.5% 的戊二醛固定细胞4 h,置摇床上用0.9% NaCL洗细胞3次。除去上清液后,用1μg/ml Hoechst 33258溶液在冰上避光处理细胞30min,然后用0.9% NaCL漂洗3次,甘油封闭后立即于荧光显微镜下(Olymus IX71)紫外光 (360 nm)激发,观察细胞核染色情况。
结果
结果
结果
结果
Fig 1 . Sporamin inhibited the wound closure of HT-29 cells in the presence of PMA. *, P<0.05 vs. PMA alone; #, P<0.05 vs. vehicle
划痕愈合实验
Fig 3. Sporamin suppressed the PMA-induced secretion of uPA in HT-29 cells after 16 h
Fig 2. Sporamin decreases adhesion of colorectal carcinoma HT-29 cells to the substrate in the presence of PMA in HT-29 cells after 16 h
Fig 4. Gelatin zymogram of conditioned medium from HT-29 cancer cells treated with 100 ng/ml PMA and various concentrations of sporamin during 4-h incubation period showing direct inhibitory effect of sporamin on MMP-9 and MMP-2 activity.

sec分离寡核苷酸孔径选择

sec分离寡核苷酸孔径选择

sec分离寡核苷酸孔径选择摘要:1.SEC 分离寡核苷酸的概述2.寡核苷酸孔径选择的重要性3.SEC 分离寡核苷酸的原理4.SEC 分离寡核苷酸的操作步骤5.SEC 分离寡核苷酸的应用案例6.SEC 分离寡核苷酸的发展前景正文:一、SEC 分离寡核苷酸的概述SEC(Size Exclusion Chromatography,尺寸排除色谱法)是一种根据样品分子大小进行分离的液相色谱技术。

在生物领域,SEC 常被用于分离寡核苷酸(oligonucleotides),寡核苷酸是具有生物学活性的核酸片段,广泛应用于基因工程、药物研发等领域。

二、寡核苷酸孔径选择的重要性寡核苷酸的孔径选择对其在生物体内的活性和功能至关重要。

合适的孔径有利于寡核苷酸的稳定性和生物活性,而不合适的孔径可能导致寡核苷酸结构不稳定,进而影响其功能。

因此,在SEC 分离过程中,选择合适的孔径对寡核苷酸的分离和纯化至关重要。

三、SEC 分离寡核苷酸的原理SEC 分离寡核苷酸的原理是根据样品中分子的大小和形状,在流动相和固定相之间产生不同的分配系数,从而实现样品的分离。

在SEC 过程中,寡核苷酸通过多孔凝胶颗粒的孔道,这些孔道具有一定的孔径。

根据寡核苷酸的大小,它们在孔道中的运动速率不同,从而达到分离的目的。

四、SEC 分离寡核苷酸的操作步骤1.样品准备:将寡核苷酸样品溶解在适当的缓冲液中,并进行过滤以去除杂质。

2.色谱柱安装:将多孔凝胶颗粒装填到色谱柱中,用缓冲液洗涤色谱柱以去除颗粒间的空气。

3.样品注入:将样品溶液注入色谱柱中,开始分离过程。

4.检测:采用紫外检测器或荧光检测器检测分离过程中的寡核苷酸。

5.数据处理:收集色谱图,根据峰面积和保留时间进行样品分析。

五、SEC 分离寡核苷酸的应用案例1.寡核苷酸库的筛选:通过SEC 技术筛选具有特定序列和功能的寡核苷酸。

2.寡核苷酸药物的研究:利用SEC 技术研究寡核苷酸药物的结构和稳定性。

乙酰麦迪霉素(明治)

乙酰麦迪霉素(明治)
3.IFの様式・作成・発行 規格はA4判、横書きとし、原則として9ポイント以上の字体で記載し、印刷は一色刷りとす る。表紙の記載項目は統一し、原則として製剤の投与経路別に作成する。IFは日病薬が策 定した「IF記載要領」に従って記載するが、本IF記載要領は、平成 11 年1月以降に承認さ れた新医薬品から適用となり、既発売品については「IF記載要領」による作成・提供が強制 されるものではない。また、再審査及び再評価(臨床試験実施による)がなされた時点なら びに適応症の拡大等がなされ、記載内容が大きく異なる場合にはIFが改訂・発行される。
4.IFの利用にあたって IF策定の原点を踏まえ、MRへのインタビュー、自己調査のデータを加えてIFの内容を充 実させ、IFの利用性を高めておく必要がある。 MRへのインタビューで調査・補足する項目として、開発の経緯、製剤的特徴、薬理作用、 臨床成績、非臨床試験等の項目が挙げられる。また、随時改訂される使用上の注意等に関す る事項に関しては、当該医薬品の製薬企業の協力のもと、医療用医薬品添付文書、お知らせ 文書、緊急安全性情報、Drug Safety Update(医薬品安全対策情報)等により薬剤師等自ら が加筆、整備する。そのための参考として、表紙の下段にIF作成の基となった添付文書の作 成又は改訂年月を記載している。なお適正使用や安全確保の点から記載されている「臨床成 績」や「主な外国での発売状況」に関する項目等には承認外の用法・用量、効能・効果が記 載されている場合があり、その取扱いには慎重を要する。
2.IFとは IFは「医療用医薬品添付文書等の情報を補完し、薬剤師等の医療従事者にとって日常業務に 必要な医薬品の適正使用や評価のための情報あるいは薬剤情報提供の裏付けとなる情報等が 集約された総合的な医薬品解説書として、日病薬が記載要領を策定し、薬剤師等のために当 該医薬品の製薬企業に作成及び提供を依頼している学術資料」と位置付けられる。 しかし、薬事法の規制や製薬企業の機密等に関わる情報、製薬企業の製剤意図に反した情報 及び薬剤師自らが評価・判断・提供すべき事項等はIFの記載事項とはならない。

一组胰蛋白酶抗性抗菌肽及其制备方法[发明专利]

一组胰蛋白酶抗性抗菌肽及其制备方法[发明专利]

专利名称:一组胰蛋白酶抗性抗菌肽及其制备方法专利类型:发明专利
发明人:王建华,毛若雨,滕达,王秀敏,郝娅
申请号:CN201510187387.0
申请日:20150421
公开号:CN106146629A
公开日:
20161123
专利内容由知识产权出版社提供
摘要:本发明提供了一组具有胰蛋白酶抗性的抗菌肽及其制备办法。

利用蛋白质定向改造技术,针对NZ2114序列中存在的六处胰蛋白酶活性位点进行有选择突变。

设计氨基酸序列为SEQ ID NO:1-SEQ ID NO:33的胰蛋白酶抗性突变体并实现其在毕赤酵母中的重组表达。

本发明首次实现
NZ2114抗胰蛋白酶衍生物的设计,经测定部分突变体(尤其是双突变体和全部三突变体)胰蛋白酶降解率显著改善,为16.67%-25%。

胰蛋白酶抗性抗菌肽对金黄色葡萄球菌
ATCC25923,ATCC43300和ATCC6538具有显著抑菌活性,MIC介于0.25-16μg/ml。

本发明所述方法获得的胰蛋白酶抗性抗菌肽可应用于抗菌药物、食品添加剂、化妆品、饲料添加剂等领域,具有广阔的应用价值和市场前景。

申请人:中国农业科学院饲料研究所
地址:100081 北京市海淀区中关村南大街12号
国籍:CN
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Xofigo 放射性治疗药剂指南说明书

Xofigo 放射性治疗药剂指南说明书

UnitedHealthcare ® Medicare AdvantagePolicy GuidelineXofigo ® Radioactive Therapeutic AgentGuideline Number : MPG356.09Approval Date : November 8, 2023 Terms and ConditionsTable of Contents Page Policy Summary ............................................................................. 1 Applicable Codes .......................................................................... 1 References ..................................................................................... 2 Guideline History/Revision Information ....................................... 2 Purpose .......................................................................................... 3 Terms and Conditions . (3)See PurposeOverviewXofigo ® (radium Ra 223 dichloride) injection is an alpha particle-emitting radioactive therapeutic agent which mimics calcium and forms complexes with hydroxyapatite at areas of increased bone turnover, such as bone metastases.GuidelinesThe U.S. Food and Drug Administration (FDA) approved radium Ra 223 dichloride (Xofigo ® Injection, Bayer HealthCare Pharmaceuticals Inc.) for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bonemetastases and no known visceral metastatic disease.The recommended dose and schedule for Xofigo ® is 55 kBq/kg (1.49 microcuries/kg) administered by slow intravenous injection over 1 minute every 4 weeks for 6 doses.The following list(s) of procedure and/or diagnosis codes is provided for reference purposes only and may not be all inclusive. Listing of a code in this guideline does not imply that the service described by the code is a covered or non-covered health service. Benefit coverage for health services is determined by the member specific benefit plan document and applicable laws that may require coverage for a specific service. The inclusion of a code does not imply any right to reimbursement or guarantee claim payment. Other Policies and Guidelines may apply.CPT Code Description 79101 Radiopharmaceutical therapy, by intravenous administrationCPT ® is a registered trademark of the American Medical AssociationHCPCS Code DescriptionA9606 Radium RA-223 dichloride, therapeutic, per microcurieDiagnosis Code DescriptionC61Malignant neoplasm of prostateRelated Medicare Advantage Reimbursement Policy • Add-on Codes Policy, ProfessionalDiagnosis CodeDescriptionAnd at least one of the following:C79.51 Secondary malignant neoplasm of boneC79.52 Secondary malignant neoplasm of bone marrowCMS Local Coverage Determinations (LCDs) and ArticlesLCDArticleContractor Medicare Part A Medicare Part BN/A A54559 Billing and Coding: Xofigo Billing Instructions PalmettoAL, GA, NC, SC,TN, VA, WV N/AA55052 Billing and Coding: Radiopharmaceutical Agents Retired 12/29/2022WPSAK, AL, AR, AZ, CA, CO, CT, DE, FL, GA, HI, IA, ID, IL, IN, KS, KY, LA, MA, MD, ME, MI, MO, MS, MT, NC, ND, NE, NH, NJ, NM, NV, OH, OK, OR, PA, RI, SC, SD, TN, TX, UT, VA, VT, WA, WI, WV, WYIA, IN, KS, MI, MO, NECMS Benefit Policy ManualChapter 15; § 50 Drugs and BiologicalsCMS Claims Processing ManualChapter 12; § 30.5 Payment for Codes for Chemotherapy Administration and Nonchemotherapy Injections and Infusions Chapter 14; § 10 General Ambulatory Surgical CenterChapter 17; § 90.2 Drugs, Biologicals, and RadiopharmaceuticalsOther(s)CGS Website (Submitting Claims for Xofigo/Radium 223)CMS HCPCS Codes for which ASP Reporting is in Units of Measure Other Than an NDC, Updated July 2023, CMS Website Xofigo Package Insert, Bayer Healthcare Pharmaceuticals WebsiteRevisions to this summary document do not in any way modify the requirement that services be provided and documented in accordance with the Medicare guidelines in effect on the date of service in question.Date Summary of Changes11/08/2023Policy Summary OverviewRemoved and relocated language pertaining to the U.S. Food and Drug Administration (FDA)approval of radium Ra 223 dichloride (Xofigo ® Injection, Bayer HealthCare Pharmaceuticals Inc.) usage (refer to the Guidelines section) GuidelinesRevised language to indicate:Date Summary of Changeso The U.S. Food and Drug Administration (FDA) approved radium Ra 223 dichloride (Xofigo®Injection, Bayer HealthCare Pharmaceuticals Inc.) for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases and no known visceralmetastatic diseaseo The recommended dose and schedule for Xofigo® is 55 kBq/kg (1.49 microcuries/kg)administered by slow intravenous injection over 1 minute every 4 weeks for 6 dosesSupporting InformationUpdated References section to reflect the most current informationArchived previous policy version MPG356.08The Medicare Advantage Policy Guideline documents are generally used to support UnitedHealthcare Medicare Advantage claims processing activities and facilitate providers’ submission of accurate claims for the specified services. The document can be used as a guide to help determine applicable:Medicare coding or billing requirements, and/orMedical necessity coverage guidelines; including documentation requirements.UnitedHealthcare follows Medicare guidelines such as NCDs, LCDs, LCAs, and other Medicare manuals for the purposes of determining coverage. It is expected providers retain or have access to appropriate documentation when requested to support coverage. Please utilize the links in the References section above to view the Medicare source materials used to develop this resource document. This document is not a replacement for the Medicare source materials that outline Medicare coverage requirements. Where there is a conflict between this document and Medicare source materials, the Medicare source materials will apply.The Medicare Advantage Policy Guidelines are applicable to UnitedHealthcare Medicare Advantage Plans offered by UnitedHealthcare and its affiliates.These Policy Guidelines are provided for informational purposes, and do not constitute medical advice. Treating physicians and healthcare providers are solely responsible for determining what care to provide to their patients. Members should always consult their physician before making any decisions about medical care.Benefit coverage for health services is determined by the member specific benefit plan document* and applicable laws that may require coverage for a specific service. The member specific benefit plan document identifies which services are covered, which are excluded, and which are subject to limitations. In the event of a conflict, the member specific benefit plan document supersedes the Medicare Advantage Policy Guidelines.Medicare Advantage Policy Guidelines are developed as needed, are regularly reviewed and updated, and are subject to change. They represent a portion of the resources used to support UnitedHealthcare coverage decision making. UnitedHealthcare may modify these Policy Guidelines at any time by publishing a new version of the policy on this website. Medicare source materials used to develop these guidelines include, but are not limited to, CMS National Coverage Determinations (NCDs), Local Coverage Determinations (LCDs), Medicare Benefit Policy Manual, Medicare Claims Processing Manual, Medicare Program Integrity Manual, Medicare Managed Care Manual, etc. The information presented in the Medicare Advantage Policy Guidelines is believed to be accurate and current as of the date of publication and is provided on an "AS IS" basis. Where there is a conflict between this document and Medicare source materials, the Medicare source materials will apply.You are responsible for submission of accurate claims. Medicare Advantage Policy Guidelines are intended to ensure that coverage decisions are made accurately based on the code or codes that correctly describe the health care services provided. UnitedHealthcare Medicare Advantage Policy Guidelines use Current Procedural Terminology (CPT®), Centers for Medicare andMedicaid Services (CMS), or other coding guidelines. References to CPT® or other sources are for definitional purposes only and do not imply any right to reimbursement or guarantee claims payment.Medicare Advantage Policy Guidelines are the property of UnitedHealthcare. Unauthorized copying, use, and distribution of this information are strictly prohibited.*For more information on a specific member's benefit coverage, please call the customer service number on the back of the member ID card or refer to the Administrative Guide.。

GMP常用英语单词

GMP常用英语单词

Abbreviated New drug简化申请的新药Accelerated approval加速批准Adverse effcet副作用Adverse reaction不良反应Agency审理部门ANDA(Abbreviated New drug application)简化新药申请Animal trial动物试验Archival copy存档用副本Batch production records生产批号记录Batch production批量生产CFR (Code of federal regulation )(美)联邦法规Clinical trial临床试验COS/CEP欧洲药典符合性认证Dietary supplement食品补充品DMF(Drug master file)药物主文件Drug substance原料药Generic name非专利名称ICH(International Conference onHarmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use)人用药物注册技术要求国际协调会议IND(Investigation new drug)临床研究申请(指申报阶段,相对于NDA);研究中的新药(指新药开发阶段,相对于新药而言,即临床前研究结束)Informed consent知情同意INN(international nonproprietary name)国际非专有名称Investigator研究人员;调研人员Labeled amount标示量NDA(New drug application)新药申请NF(National formulary)(美)国家药品集NIH(National Institute of Health)(美)国家卫生研究所Panel专家小组preparing and Submitting起草和申报Prescription drug处方药Proprietary name专有名称Regulatory methodology质量管理方法Regulatory methods validation管理用分析方法的验证Regulatory specification质量管理规格标准Review copy审查用副本Sponsor主办者(指负责并着手临床研究者)Standard drug标准药物Strength规格;规格含量(每一剂量所含有效成分的量)Submission申报;递交Treatment IND研究中的新药用于治疗生产工艺相关Acceptance criteria可接受标准air driers手烘箱Airlock Room气闸室analytical methods分析方法anhydrous无水API原料药Assay 含量at rest静态batch size批量Blending Batches混批Blending Room总混间calibrating校正case-by-case具体分析centigrate摄氏度Changing Room更衣室Charge-in进料chemical properties化学性质Clarity,completeness,or PH of solutions溶液的澄明度、溶解完全性及PH值cleaning agents清洗媒介cleaning procedures清洁程序Cleaning Tools Room洁具室Coating Mixture Preparing Room配浆间Commercial scale可配伍性Concentrated Solution Room浓配室consistency of the process工艺的稳定性critical process关键步骤dedicated专用的Documentation System文件系统dosage form剂型electronic form电子格式electronicsignatures电子签名Emergency Door安全门established schedule预先计划Excipient辅料exhaust排气fermentation发酵Granulation颗粒HAVC(Heating ventilation and air conditioning)空调净化系统Heavy metal重金属historical date历史数据Hydrochloric acid盐酸in operation动态incoming materials进厂物料in-house testing内控检测installation qualification(IQ)安装确认intermediate中间体intermal audits self-inspection自检laboratory control record实验室控制记录laboratory information managementsystem(LIMS)实验室信息管理系统local authorities当地药政部门Loss on drying干燥失重Meet the requirement符合要求Melting point熔点Melting range熔程microbiological specifications微生物标准microorganisms微生物Milling磨粉Mix-ups混放modified facilities设施变更molecular formula分子式Non-dedicated equipment非专用设备Operational qualification(OQ)运行确认Out-of-specification不合格Packaging包装Particle size粒度Perform a blank determination作一个空白对照Personnel Hygiene人员卫生pilot scale中试规模potable water饮用水premises设施process parameters工艺参数Process validation工艺验证,过程验证product quality reviews产品质量回顾production batch records批生产记录proposed indication适应症purification纯化performance qualification(PQ)性能确认Process flow diagrams(PFDS)工艺流程图product validation产品验证regulatory inspection evaluation药政检查Related substance有关物质release放行Residual solvents残留溶剂retention periods保留期限Retention samples留样retention time保留时间Retrospective validation回顾性验证Revalidation再验证review and approve审核并批准route of administration给药途径Sanitation环境卫生scale-up reports报产报告serious GMP deficiencies严重GMP缺陷Sip sterilization in place在线灭菌sodium hydroxide氢氧化钠Specific rotation比旋度specifications标准stability date稳定性数据stability monitoring program稳定性监控计划status状态sterile APIs无菌原料药sterilization消毒succ essive batches连续批号supplier供应商technical transfer技术转化total microbial counts微生物总数traceable可追踪的turnover packages验证文件集Validation master plan验证总计划Validation report验证报告常用中译英系统system物料平衡reconciliation批batch or lot批号batch number批生产记录batch records文件document标准操作规程standard operating proceddures (SOP)生产工艺规程master formula工艺用水water for processing纯化水purified water注射用水water for injection状态标志status mark/label中间产品intermediate product理论产量theoretical yield物料material待验quarantine起始原料staring material洁净室(区)clean room(zone)待包品bulk product成品finished product灭菌sterilization控制点control point质量监督quality surveillance生产过程控制in-process control退货returned product拒收rejected交叉污染cross contamination放行released质量要求quality requirement可追溯性traceability计量确认metrologial confirmation人员净化室room for cleaning human body物料净化室room for cleaning material悬浮粒子airborne particles洁净度cleanliness净化cleaning传递箱pass box洁净服clean working garment洁净工作台clean bench静态at-rest动态operational粗效过滤器roughing filter中效过滤器medium efficiency filter高效过滤器hepa filter安装确认instalation qualification(IQ)运行确认operational qualification(OQ)性能确认performance qualification(PQ)工艺验证process validation。

dda label-free实验需要注意的参数

dda label-free实验需要注意的参数

dda label-free实验需要注意的参数DDA(data-dependent acquisition,即数据依赖采集)是质谱技术中常用的一种实验方法,可以用于定性和定量分析。

与DDA不同,DDA Label-free实验则是一种无标记的质谱实验方法,可以用于比较不同样本之间的蛋白质表达差异。

在进行DDA Label-free实验时,需要注意一些关键的参数,以确保实验的准确性和可靠性。

以下是一些需要注意的参数:1.选择质谱仪和色谱柱:质谱仪和色谱柱的选择对实验结果具有重要影响。

质谱仪应具有高分辨率和灵敏度,能够准确检测低丰度蛋白质。

色谱柱的分离能力和保留性能也非常重要,可以选择适合目标样品的色谱柱。

2.样品制备:样品制备是DDA Label-free实验的关键步骤之一。

在制备过程中,需要注意样品的完整性和一致性。

样品制备应遵循标准的蛋白质提取、纯化和浓缩方法,以确保样品中目标蛋白质的高纯度和足够数量。

3.样品负载量:样品负载量直接影响到实验的灵敏度和检测深度。

负载量过低会导致低信号强度,负载量过高则可能会引发样品混杂和信号饱和。

因此,需要进行一系列的样品负载量优化实验,选择适当的负载量进行实验。

4.梯度条件:色谱梯度条件对于有效的样品分离和质谱检测非常重要。

需要优化洗脱梯度的时间和浓度,在保证样品分离的同时,尽可能提高蛋白质检测的灵敏度和覆盖度。

5.质谱仪参数设置:质谱仪的参数设置对实验结果具有重要影响。

需要优化离子传输管电压、碎裂能量、测定区域、离子选择反应参数等参数,以最大程度提高质谱信号和信息的质量。

6.数据分析:DDA Label-free实验的数据分析是实验的最后一步,也是最关键的一步。

需要使用专业的数据分析软件,如MaxQuant、Proteome Discoverer等,对质谱数据进行准确的鉴定和定量分析。

同时,需要进行统计分析,筛选出显著差异表达的蛋白质。

7.质控实验:为了确保实验的准确性和可重复性,需要进行一些质控实验。

高效液相色谱法测定注射用美罗培南的有关物质

高效液相色谱法测定注射用美罗培南的有关物质

第35卷第3期 长治医学院学报2021 年 6 月JOURNAL OF CHANGZHI MEDICAI COLLEGE167Vol. 35 No. 3Jun. 2021高效液相色谱法测定注射用美罗培南的有关物质李金格禹玉洪**作者单位山西医科大学药学院药剂教研室(030001)* 通信作者(E-mail :3024546064@ qq. com)摘要目的:探讨优化注射用美罗培南杂质A 、B 的测定方法。

方法:运用高效液相色谱法(HPLC) 进行检测,色谱柱以十八烷基硅烷键合硅胶为填充剂;流动相A :20. 0 mmol-L'1磷酸二氢钠-甲醇(89 :11, V/V),流动相B :甲醇,流速1.0 mL-min 1,检测波长220 nm,柱温30 P 。

结果:主成分峰与杂质峰可实现基线分离,杂质A 检测限和定量限分别为1. 62,5.15 ng,杂质B 检测限和定量限分别为0. 85,2. 51 ng ;1.2~24.0 ixg-mL -1的杂质A 具有良好的线性关系(r=0. 999 9) ,0.7-14.0 ixg-mL 1的杂质B 具有良好的线性 关系(r=0. 999 9);杂质A 平均加样回收率为101.2%(RSD= 1.38%,“ = 9),杂质B 平均加样回收率为100.2%(RSD=1.29%,n = 9)o 经破坏性试验,美罗培南可能的降解杂质A 、B 均不干扰美罗培南主峰的测定。

结论:检测限及定量限、精密度、稳定性、耐用性试验结果均符合HPLC 有关物质测定的方法学验证要求。

本HPLC 法专属性良好,可用于美罗培南的主要杂质A 、B 的定量控制。

关键词美罗培南;有关物质;高效液相色谱法中图分类号R97&1文献标识码 A 文章编号1006(2021)03-167-05Determination of Related Substances of Meropenem for Injection by High Performance Liquid ChromatographyLI Jinge , YU YuhongDepartment of Pharmacy , School of Pharmacy , Shanxi Medical UniversityAbstract Objective : To explore and optimize the determination method of impulity A andB of meropenem for injection. Meth ­ods :Using the high performance liquid chromatography ( HPLC ) to detection , Octadecylsilane-bonded silica gel was used as the fi ­ler ; The mobile phase A : 20. 0 mmol * L -1 sodium dihydrogen phosphate-methanol ( 89 : 11, V/V) . The mobile phase B : methanol ,the flow rate was 1. 0 mL *m in _1 and the detection wavelength was set at 220 nm. The column temperature was set at 30 % . Re ­sults :The principal component peak and impurity peak could achieve baseline separation. The detection limit and quantitative limit of impurity A were 1. 62 ng and 5. 15 ng respectively , and the detection limit and quantitative lim 让 of impurity B were 0. 85 ng and 2. 51 ng respectively. There was A good linear relationship between impurity A (r = 0. 999 9) and impurity B ( r= 0. 999 9 ) in therange of 1. 2-24. 0 |xg *m L _1 and 0. 7 ~ 14. 0 jig * mL -1. The average recovery of impurity A was 101. 2% ( RSD = 1. 38% , n = 9),and that of impurity B was 100. 2% ( RSD = 1. 29% , n= 9). After stressing test, both of impurities A and B of meropenem didn * tinterfere w 让h the determination of meropenem main peak. Conclusion : The test results of detection lim 让 and quant N ative lim 让,pre ­cision ,stabil 让y and durability all meet the methodological verification requirements of HPLC related substance determination. The HPLC method has good specificity and can be used for the quant N ative control of major impurities A and B.Key words meropenem ; related substances ; HPLC注射用美罗培南(Meropenem, C ”H25弘0申) 是由日本住友制药公司与英国ICI 制药公司共同 开发的第二代碳青霉烯抗生素,通过干扰细菌细胞壁的合成发挥杀菌作用,具有广谱耐酶的特 点[1_4]o 在美罗培南原料中常检测出杂质A 及杂质B,杂质A(C 17H 27N 3O 6S)为美罗培南四元内酰 胺环结构发生水解反应而形成,系美罗培南的降 解产物;杂质B(C 34H 50N 6O 10S 2)为美罗培南与杂质A 发生聚合反应而形成,系美罗培南的二聚体X 。

【R高级教程】专题二:差异表达基因的分析

【R高级教程】专题二:差异表达基因的分析

【R高级教程】专题二:差异表达基因的分析应学生及个别博友的要求,尽管专业博文点击率和反应均很差,但在去San Diego参加PAG会议之前,还是抽时间给出【R高级教程】的第二专题。

专题一给出了聚类分析的示例,本专题主要谈在表达谱芯片分析中如何利用Bioconductor鉴定差异表达基因。

鉴定差异表达基因是表达谱芯片分析pipeline中必须的分析步骤。

差异表达基因分析是根据表型协变量(分类变量)鉴定组间差异表达,它属于监督性分类的一种。

在鉴定差异表达基因以前,一般需要对表达值实施非特异性过滤(在机器学习框架下属于非监督性分类),因为适当的非特异性过滤可以提高差异表达基因的检出率、甚至是功效。

R分析差异表达基因的library有很多,但目前运用最广泛的Bioconductor包是limma。

本专题示例依然来自GEO数据库中检索号为GSE11787 的Affymetrix芯片的数据,数据介绍参阅专题一。

>library(limma)>design <- model.matrix(~ -1+factor(c(1,1,1, 2,2,2)))这个是根据芯片试验设计,对表型协变量的水平进行design,比如本例中共有6张芯片,前3张为control对照组,后3张芯片为实验处理组,用1表示对照组,用2表示处理组。

其他试验设计同理,比如2*2的因子设计试验,如果每个水平技术重复3次,那么可以表示为:design <- model.matrix(~ -1+factor(c(1,1,1, 2,2,2,3,3,3, 4,4,4)))。

接上面的程序语句继续:>colnames(design) <- c("control", "LPS")>fit <- lmFit(eset2, design)>contrast.matrix <- makeContrasts(control-LPS, levels=design)>fit <- eBayes(fit)>fit2 <- contrasts.fit(fit, contrast.matrix)>fit2 <- eBayes(fit2)>results<-decideTests(fit2, method="global", adjust.method="BH",p.value=0.01, lfc=1.5)>summary(results)>vennCounts(results)>vennDiagram(results)比较遗憾的是,目前limma自带的venn作图函数不能做超过3维的高维venn图,只能画出3个圆圈的venn图,即只能同时对三个coef进行venn作图。

matK序列在绞股蓝及其混伪品中的应用

matK序列在绞股蓝及其混伪品中的应用

matK序列在绞股蓝及其混伪品中的应用徐林赵芳杨贵清尹鑫徐其碧赵月梅*(贵州师范学院生物科学学院,贵州贵阳550018)摘要用matK序列作为DNA条形码来区分绞股蓝及其混伪品雪胆、锥形果、棒槌瓜、乌蔹梅和崖爬藤。

通过PCR扩增测序和在GenBank中下载的方式共获得16条matK序列,经比对后,用MEGA6.0计算种间的K2P距离并基于该距离建立了系统发育邻接树(NJ),并计算了“barcode gap”。

结果显示,绞股蓝与其混伪品雪胆、锥形果、棒槌瓜、乌蔹梅、崖爬藤种内种间遗传距离区分明显,可形成一个“gap”,系统发育树中6个物种中分成了两大支,葫芦科物种绞股蓝、雪胆、锥形果和棒槌瓜聚成了一支,葡萄科物种乌蔹梅和崖爬藤聚成了另一支,绞股蓝样品聚为单系并能够与其混淆品明显区分开。

表明matK序列可作为区分绞股蓝和其常见混伪品的参考DNA条形码。

关键词matK;绞股蓝;伪品;DNA条形码中图分类号R282.5文献标识码A文章编号1007-7731(2023)07-0022-04绞股蓝,又名五叶参、七叶胆、公罗锅底、遍地生根等,为葫芦科绞股蓝属的多年生草质藤本植物[1]。

全草入药,具有补气养阴、清肺化痰、养心安神之功效,又名“南方人参”。

绞股蓝疗效显著,市场前景广阔,引发了科研和开发热潮[2]。

由于多种植物在形态上与绞股蓝极为相似,不容易分辨,导致绞股蓝临床药材来源复杂,严重影响了临床用药的安全性和加工产品的质量。

如同科植物雪胆,不仅与绞股蓝形态相似,分布区域与生长环境也非常相近,野外采集时尤其在营养生长期,易将其与绞股蓝混淆[3-4];棒槌瓜、锥形果是绞股蓝药材在葫芦科中常见的混淆品[5];此外,葡萄科植物乌蔹莓、崖爬藤营养器官的形态也与绞股蓝也极其相似,将乌蔹莓误作绞股蓝采集的现象时有发生[6]。

DNA条形码技术由Hebert等[7]于2003年正式提出,是指利用一个或少数几个标准的DNA片段快速、准确识别和鉴定植物物种的技术[8]。

苏州格锐思生物科技有限公司丙二醛(MDA)含量测试盒说明书

苏州格锐思生物科技有限公司丙二醛(MDA)含量测试盒说明书

丙二醛(malondialdehyde,MDA)含量测试盒说明书(货号:G0109F分光法48样)一、产品简介:丙二醛(MDA)是由于生物体官衰老或在逆境条件下受伤害,其组织或器官膜脂质发生过氧化反应而产生的。

它的含量与生物体衰老及逆境伤害有密切关系。

MDA在高温、酸性条件下,与硫代巴比妥酸(thiobarbituric acid,TBA)缩合,生成红色产物,在532nm有最大吸收峰,进行比色后可估测样品中过氧化脂质的含量;同时测定600nm下的吸光度,利用532nm与600nm下的吸光度的差值计算MDA的含量。

二、试剂盒的组分与配制试剂名称规格保存要求备注提取液液体60mL×1瓶4℃保存工作液液体30mL×1瓶4℃避光保存若有沉淀析出,可50℃水浴10min,溶解备用三、所需的仪器和用品:可见分光光度计、1mL玻璃比色皿(光径1cm)、水浴锅、台式离心机、可调式移液器、研钵、冰和蒸馏水。

四、丙二醛(MDA)的测定:建议正式实验前选取2个样本做预测定,了解本批样品情况,熟悉实验流程,避免实验样本和试剂浪费!1、样本制备:①组织样本:称取约0.1g组织(水分充足的样本可取0.5g),加入1mL提取液,进行冰浴匀浆。

4℃×12000rpm离心10min,取上清,置冰上待测。

【注】:若增加样本量,可按照组织质量(g):提取液体积(mL)为1:5~10的比例进行提取。

②细菌/细胞样本:先收集细菌或细胞到离心管内,离心后弃上清;取500万细菌或细胞加入1mL提取液,在4ºC或冰浴进行匀浆(或使用各类常见电动匀浆器)。

4ºC约12,000rpm离心10min,取上清作为待测样品。

【注】:若增加样本量,可按照细菌/细胞数量(104):提取液(mL)为500~1000:1的比例进行提取。

③液体样本:直接检测。

若浑浊,离心后取上清检测。

2、上机检测①打开分光光度计预热30min,蒸馏水调零,同时水浴锅加热到90-95℃。

加拿大拟定肟菌酯的最大残留限量

加拿大拟定肟菌酯的最大残留限量

加拿大拟定肟菌酯的最大残留限量
2008年5月20日,加拿大卫生部有害生物管理局(PMRA)拟定肟菌酯(Trifloxystrobin)最大残留限量。

目前,加拿大的最大残留限量是通过官方公报进行磋商后,根据食品药物法规(FDR)制定的。

通过Bill C-28对食品药物法的修订,预计于2008年生效,这将允许按照有害生物控制产品法合法的制定杀虫剂最大残留限量,而无须经过FDA所属法规的批准。

本文件的目的是对所列肟菌酯(Trifloxystrobin),包括代谢物CGA-321113的MRLs进行咨询,这些限量是在PCPA于2008年6月28日生效后由PMRA拟定的。

咨询活动已经在Bill C-28生效之前开始,以便在FDA被修改后尽快合法的制定本文件所列的MRLs。

(注意:在将有关杀虫剂最大残留限量立法从食品药物法案过渡为有害生物控制产品法案(对拟定最大残留限量的磋商(PMRL2006-01))的文件中拟定的0.04ppm最大残留限量在G/SPS/N/CAN/276中通报)。

所列产品补充了作物14组核果的最大残留限量。

剂量依赖性敏感简介

剂量依赖性敏感简介

剂量依赖性敏感简介
目录
•1拼音
•2英文参考
•3注解
•4参考资料
1拼音
jì liàng yī lài xìng mǐn gǎn
2英文参考
susceptibledose dependent[WS/T 421—2013 抗酵母样真菌药物敏感性试验肉汤稀释法]
SDD[WS/T 421—2013 抗酵母样真菌药物敏感性试验肉汤稀释法]
3注解
剂量依赖性敏感(susceptibledose dependent;SDD)是指当使用比常规用药更高剂量或更高血药浓度时能够取得疗效[1]。

4参考资料
1.^ [1] 中华人民共和国国家卫生和计划生育委员会.WS/T 421—2013 抗酵母样真菌药物敏感性试验肉汤稀释法[Z].20130716.
免责声明:本文内容来源于网络,不保证100%正确,涉及到药方及用法用量的问题,不保证正确,仅供参考。

由此造成的问题,本站概不负责。

Reproduction numbers and sub-threshold endemic equilibria for compartmental models of disease trans

Reproduction  numbers and sub-threshold endemic equilibria for compartmental models of disease trans

Reproduction numbers and sub-threshold endemicequilibria for compartmental models of disease transmissionP.van den Driesschea,1,James Watmough b,*,2aDepartment of Mathematics and Statistics,University of Victoria,Victoria,BC,Canada V8W 3P4b Department of Mathematics and Statistics,University of New Brunswick,Fredericton,NB,Canada E3B 5A3Received 26April 2001;received in revised form 27June 2001;accepted 27June 2001Dedicated to the memory of John JacquezAbstractA precise definition of the basic reproduction number,R 0,is presented for a general compartmental disease transmission model based on a system of ordinary differential equations.It is shown that,if R 0<1,then the disease free equilibrium is locally asymptotically stable;whereas if R 0>1,then it is unstable.Thus,R 0is a threshold parameter for the model.An analysis of the local centre manifold yields a simple criterion for the existence and stability of super-and sub-threshold endemic equilibria for R 0near one.This criterion,together with the definition of R 0,is illustrated by treatment,multigroup,staged progression,multistrain and vector–host models and can be applied to more complex models.The results are significant for disease control.Ó2002Elsevier Science Inc.All rights reserved.Keywords:Basic reproduction number;Sub-threshold equilibrium;Disease transmission model;Disease control1.IntroductionOne of the most important concerns about any infectious disease is its ability to invade a population.Many epidemiological models have a disease free equilibrium (DFE)at whichtheMathematical Biosciences 180(2002)29–48/locate/mbs*Corresponding author.Tel.:+1-5064587323;fax:+1-5064534705.E-mail addresses:pvdd@math.uvic.ca (P.van den Driessche),watmough@unb.ca (J.Watmough).URL:http://www.math.unb.ca/$watmough.1Research supported in part by an NSERC Research Grant,the University of Victoria Committee on faculty research and travel and MITACS.2Research supported by an NSERC Postdoctoral Fellowship tenured at the University of Victoria.0025-5564/02/$-see front matter Ó2002Elsevier Science Inc.All rights reserved.PII:S0025-5564(02)00108-630P.van den Driessche,J.Watmough/Mathematical Biosciences180(2002)29–48population remains in the absence of disease.These models usually have a threshold parameter, known as the basic reproduction number,R0,such that if R0<1,then the DFE is locally as-ymptotically stable,and the disease cannot invade the population,but if R0>1,then the DFE is unstable and invasion is always possible(see the survey paper by Hethcote[1]).Diekmann et al.[2]define R0as the spectral radius of the next generation matrix.We write down in detail a general compartmental disease transmission model suited to heterogeneous populations that can be modelled by a system of ordinary differential equations.We derive an expression for the next generation matrix for this model and examine the threshold R0¼1in detail.The model is suited to a heterogeneous population in which the vital and epidemiological parameters for an individual may depend on such factors as the stage of the disease,spatial position,age or behaviour.However,we assume that the population can be broken into homo-geneous subpopulations,or compartments,such that individuals in a given compartment are indistinguishable from one another.That is,the parameters may vary from compartment to compartment,but are identical for all individuals within a given compartment.We also assume that the parameters do not depend on the length of time an individual has spent in a compart-ment.The model is based on a system of ordinary equations describing the evolution of the number of individuals in each compartment.In addition to showing that R0is a threshold parameter for the local stability of the DFE, we apply centre manifold theory to determine the existence and stability of endemic equilib-ria near the threshold.We show that some models may have unstable endemic equilibria near the DFE for R0<1.This suggests that even though the DFE is locally stable,the disease may persist.The model is developed in Section2.The basic reproduction number is defined and shown to bea threshold parameter in Section3,and the definition is illustrated by several examples in Section4.The analysis of the centre manifold is presented in Section5.The epidemiological ramifications of the results are presented in Section6.2.A general compartmental epidemic model for a heterogeneous populationConsider a heterogeneous population whose individuals are distinguishable by age,behaviour, spatial position and/or stage of disease,but can be grouped into n homogeneous compartments.A general epidemic model for such a population is developed in this section.Let x¼ðx1;...;x nÞt, with each x i P0,be the number of individuals in each compartment.For clarity we sort the compartments so that thefirst m compartments correspond to infected individuals.The distinc-tion between infected and uninfected compartments must be determined from the epidemiological interpretation of the model and cannot be deduced from the structure of the equations alone,as we shall discuss below.It is plausible that more than one interpretation is possible for some models.A simple epidemic model illustrating this is given in Section4.1.The basic reproduction number can not be determined from the structure of the mathematical model alone,but depends on the definition of infected and uninfected compartments.We define X s to be the set of all disease free states.That isX s¼f x P0j x i¼0;i¼1;...;m g:In order to compute R0,it is important to distinguish new infections from all other changes inpopulation.Let F iðxÞbe the rate of appearance of new infections in compartment i,Vþi ðxÞbe therate of transfer of individuals into compartment i by all other means,and VÀi ðxÞbe the rate oftransfer of individuals out of compartment i.It is assumed that each function is continuously differentiable at least twice in each variable.The disease transmission model consists of non-negative initial conditions together with the following system of equations:_x i¼f iðxÞ¼F iðxÞÀV iðxÞ;i¼1;...;n;ð1Þwhere V i¼VÀi ÀVþiand the functions satisfy assumptions(A1)–(A5)described below.Sinceeach function represents a directed transfer of individuals,they are all non-negative.Thus,(A1)if x P0,then F i;Vþi ;VÀiP0for i¼1;...;n.If a compartment is empty,then there can be no transfer of individuals out of the compartment by death,infection,nor any other means.Thus,(A2)if x i¼0then VÀi ¼0.In particular,if x2X s then VÀi¼0for i¼1;...;m.Consider the disease transmission model given by(1)with f iðxÞ,i¼1;...;n,satisfying con-ditions(A1)and(A2).If x i¼0,then f iðxÞP0and hence,the non-negative cone(x i P0, i¼1;...;n)is forward invariant.By Theorems1.1.8and1.1.9of Wiggins[3,p.37]for each non-negative initial condition there is a unique,non-negative solution.The next condition arises from the simple fact that the incidence of infection for uninfected compartments is zero.(A3)F i¼0if i>m.To ensure that the disease free subspace is invariant,we assume that if the population is free of disease then the population will remain free of disease.That is,there is no(density independent) immigration of infectives.This condition is stated as follows:(A4)if x2X s then F iðxÞ¼0and VþiðxÞ¼0for i¼1;...;m.The remaining condition is based on the derivatives of f near a DFE.For our purposes,we define a DFE of(1)to be a(locally asymptotically)stable equilibrium solution of the disease free model,i.e.,(1)restricted to X s.Note that we need not assume that the model has a unique DFE. Consider a population near the DFE x0.If the population remains near the DFE(i.e.,if the introduction of a few infective individuals does not result in an epidemic)then the population will return to the DFE according to the linearized system_x¼Dfðx0ÞðxÀx0Þ;ð2Þwhere Dfðx0Þis the derivative½o f i=o x j evaluated at the DFE,x0(i.e.,the Jacobian matrix).Here, and in what follows,some derivatives are one sided,since x0is on the domain boundary.We restrict our attention to systems in which the DFE is stable in the absence of new infection.That is, (A5)If FðxÞis set to zero,then all eigenvalues of Dfðx0Þhave negative real parts.P.van den Driessche,J.Watmough/Mathematical Biosciences180(2002)29–4831The conditions listed above allow us to partition the matrix Df ðx 0Þas shown by the following lemma.Lemma 1.If x 0is a DFE of (1)and f i ðx Þsatisfies (A1)–(A5),then the derivatives D F ðx 0Þand D V ðx 0Þare partitioned asD F ðx 0Þ¼F 000 ;D V ðx 0Þ¼V 0J 3J 4;where F and V are the m Âm matrices defined byF ¼o F i o x j ðx 0Þ !and V ¼o V i o x jðx 0Þ !with 16i ;j 6m :Further ,F is non-negative ,V is a non-singular M-matrix and all eigenvalues of J 4have positive real part .Proof.Let x 02X s be a DFE.By (A3)and (A4),ðo F i =o x j Þðx 0Þ¼0if either i >m or j >m .Similarly,by (A2)and (A4),if x 2X s then V i ðx Þ¼0for i 6m .Hence,ðo V i =o x j Þðx 0Þ¼0for i 6m and j >m .This shows the stated partition and zero blocks.The non-negativity of F follows from (A1)and (A4).Let f e j g be the Euclidean basis vectors.That is,e j is the j th column of the n Ân identity matrix.Then,for j ¼1;...;m ,o V i o x jðx 0Þ¼lim h !0þV i ðx 0þhe j ÞÀV i ðx 0Þh :To show that V is a non-singular M-matrix,note that if x 0is a DFE,then by (A2)and (A4),V i ðx 0Þ¼0for i ¼1;...;m ,and if i ¼j ,then the i th component of x 0þhe j ¼0and V i ðx 0þhe j Þ60,by (A1)and (A2).Hence,o V i =o x j 0for i m and j ¼i and V has the Z sign pattern (see Appendix A).Additionally,by (A5),all eigenvalues of V have positive real parts.These two conditions imply that V is a non-singular M-matrix [4,p.135(G 20)].Condition (A5)also implies that the eigenvalues of J 4have positive real part.Ã3.The basic reproduction numberThe basic reproduction number,denoted R 0,is ‘the expected number of secondary cases produced,in a completely susceptible population,by a typical infective individual’[2];see also [5,p.17].If R 0<1,then on average an infected individual produces less than one new infected individual over the course of its infectious period,and the infection cannot grow.Conversely,if R 0>1,then each infected individual produces,on average,more than one new infection,and the disease can invade the population.For the case of a single infected compartment,R 0is simply the product of the infection rate and the mean duration of the infection.However,for more complicated models with several infected compartments this simple heuristic definition of R 0is32P.van den Driessche,J.Watmough /Mathematical Biosciences 180(2002)29–48insufficient.A more general basic reproduction number can be defined as the number of new infections produced by a typical infective individual in a population at a DFE.To determine the fate of a‘typical’infective individual introduced into the population,we consider the dynamics of the linearized system(2)with reinfection turned off.That is,the system _x¼ÀD Vðx0ÞðxÀx0Þ:ð3ÞBy(A5),the DFE is locally asymptotically stable in this system.Thus,(3)can be used to de-termine the fate of a small number of infected individuals introduced to a disease free population.Let wi ð0Þbe the number of infected individuals initially in compartment i and letwðtÞ¼w1ðtÞ;...;w mðtÞðÞt be the number of these initially infected individuals remaining in the infected compartments after t time units.That is the vector w is thefirst m components of x.The partitioning of D Vðx0Þimplies that wðtÞsatisfies w0ðtÞ¼ÀV wðtÞ,which has the unique solution wðtÞ¼eÀVt wð0Þ.By Lemma1,V is a non-singular M-matrix and is,therefore,invertible and all of its eigenvalues have positive real parts.Thus,integrating F wðtÞfrom zero to infinity gives the expected number of new infections produced by the initially infected individuals as the vector FVÀ1wð0Þ.Since F is non-negative and V is a non-singular M-matrix,VÀ1is non-negative[4,p.137 (N38)],as is FVÀ1.To interpret the entries of FVÀ1and develop a meaningful definition of R0,consider the fate of an infected individual introduced into compartment k of a disease free population.The(j;k)entry of VÀ1is the average length of time this individual spends in compartment j during its lifetime, assuming that the population remains near the DFE and barring reinfection.The(i;j)entry of F is the rate at which infected individuals in compartment j produce new infections in compartment i. Hence,the(i;k)entry of the product FVÀ1is the expected number of new infections in com-partment i produced by the infected individual originally introduced into compartment k.Fol-lowing Diekmann et al.[2],we call FVÀ1the next generation matrix for the model and set R0¼qðFVÀ1Þ;ð4Þwhere qðAÞdenotes the spectral radius of a matrix A.The DFE,x0,is locally asymptotically stable if all the eigenvalues of the matrix Dfðx0Þhave negative real parts and unstable if any eigenvalue of Dfðx0Þhas a positive real part.By Lemma1, the eigenvalues of Dfðx0Þcan be partitioned into two sets corresponding to the infected and uninfected compartments.These two sets are the eigenvalues of FÀV and those ofÀJ4.Again by Lemma1,the eigenvalues ofÀJ4all have negative real part,thus the stability of the DFE is determined by the eigenvalues of FÀV.The following theorem states that R0is a threshold parameter for the stability of the DFE.Theorem2.Consider the disease transmission model given by(1)with fðxÞsatisfying conditions (A1)–(A5).If x0is a DFE of the model,then x0is locally asymptotically stable if R0<1,but un-stable if R0>1,where R0is defined by(4).Proof.Let J1¼FÀV.Since V is a non-singular M-matrix and F is non-negative,ÀJ1¼VÀF has the Z sign pattern(see Appendix A).Thus,sðJ1Þ<0()ÀJ1is a non-singular M-matrix;P.van den Driessche,J.Watmough/Mathematical Biosciences180(2002)29–483334P.van den Driessche,J.Watmough/Mathematical Biosciences180(2002)29–48where sðJ1Þdenotes the maximum real part of all the eigenvalues of the matrix J1(the spectral abscissa of J1).Since FVÀ1is non-negative,ÀJ1VÀ1¼IÀFVÀ1also has the Z sign pattern.Ap-plying Lemma5of Appendix A,with H¼V and B¼ÀJ1¼VÀF,we have ÀJ1is a non-singular M-matrix()IÀFVÀ1is a non-singular M-matrix:Finally,since FVÀ1is non-negative,all eigenvalues of FVÀ1have magnitude less than or equal to qðFVÀ1Þ.Thus,IÀFVÀ1is a non-singular M-matrix;()qðFVÀ1Þ<1:Hence,sðJ1Þ<0if and only if R0<1.Similarly,it follows thatsðJ1Þ¼0()ÀJ1is a singular M-matrix;()IÀFVÀ1is a singular M-matrix;()qðFVÀ1Þ¼1:The second equivalence follows from Lemma6of Appendix A,with H¼V and K¼F.The remainder of the equivalences follow as with the non-singular case.Hence,sðJ1Þ¼0if and only if R0¼1.It follows that sðJ1Þ>0if and only if R0>1.ÃA similar result can be found in the recent book by Diekmann and Heesterbeek[6,Theorem6.13].This result is known for the special case in which J1is irreducible and V is a positive di-agonal matrix[7–10].The special case in which V has positive diagonal and negative subdiagonal elements is proven in Hyman et al.[11,Appendix B];however,our approach is much simpler(see Section4.3).4.Examples4.1.Treatment modelThe decomposition of fðxÞinto the components F and V is illustrated using a simple treat-ment model.The model is based on the tuberculosis model of Castillo-Chavez and Feng[12,Eq.(1.1)],but also includes treatment failure used in their more elaborate two-strain model[12,Eq.(2.1)].A similar tuberculosis model with two treated compartments is proposed by Blower et al.[13].The population is divided into four compartments,namely,individuals susceptible to tu-berculosis(S),exposed individuals(E),infectious individuals(I)and treated individuals(T).The dynamics are illustrated in Fig.1.Susceptible and treated individuals enter the exposed com-partment at rates b1I=N and b2I=N,respectively,where N¼EþIþSþT.Exposed individuals progress to the infectious compartment at the rate m.All newborns are susceptible,and all indi-viduals die at the rate d>0.Thus,the core of the model is an SEI model using standard inci-dence.The treatment rates are r1for exposed individuals and r2for infectious individuals. However,only a fraction q of the treatments of infectious individuals are successful.Unsuc-cessfully treated infectious individuals re-enter the exposed compartment(p¼1Àq).The diseasetransmission model consists of the following differential equations together with non-negative initial conditions:_E¼b1SI=Nþb2TI=NÀðdþmþr1ÞEþpr2I;ð5aÞ_I¼m EÀðdþr2ÞI;ð5bÞ_S¼bðNÞÀdSÀb1SI=N;ð5cÞ_T¼ÀdTþr1Eþqr2IÀb2TI=N:ð5dÞProgression from E to I and failure of treatment are not considered to be new infections,but rather the progression of an infected individual through the various compartments.Hence,F¼b1SI=Nþb2TI=NB B@1C CA and V¼ðdþmþr1ÞEÀpr2IÀm Eþðdþr2ÞIÀbðNÞþdSþb1SI=NdTÀr1EÀqr2Iþb2TI=NB B@1C CA:ð6ÞThe infected compartments are E and I,giving m¼2.An equilibrium solution with E¼I¼0has the form x0¼ð0;0;S0;0Þt,where S0is any positive solution of bðS0Þ¼dS0.This will be a DFE if and only if b0ðS0Þ<d.Without loss of generality,assume S0¼1is a DFE.Then,F¼0b100;V¼dþmþr1Àpr2Àm dþr2;givingVÀ1¼1ðdþmþr1Þðdþr2ÞÀm pr2dþr2pr2m dþmþr1and R0¼b1m=ððdþmþr1Þðdþr2ÞÀm pr2Þ.A heuristic derivation of the(2;1)entry of VÀ1and R0are as follows:a fraction h1¼m=ðdþmþr1Þof exposed individuals progress to compartment I,a fraction h2¼pr2=ðdþr2Þof infectious individuals re-enter compartment E.Hence,a fractionh1of exposed individuals pass through compartment I at least once,a fraction h21h2passthroughat least twice,and a fraction h k 1h k À12pass through at least k times,spending an average of s ¼1=ðd þr 2Þtime units in compartment I on each pass.Thus,an individual introduced into com-partment E spends,on average,s ðh 1þh 21h 2þÁÁÁÞ¼s h 1=ð1Àh 1h 2Þ¼m =ððd þm þr 1Þðd þr 2ÞÀm pr 2Þtime units in compartment I over its expected lifetime.Multiplying this by b 1gives R 0.The model without treatment (r 1¼r 2¼0)is an SEI model with R 0¼b 1m =ðd ðd þm ÞÞ.The interpretation of R 0for this case is simpler.Only a fraction m =ðd þm Þof exposed individuals progress from compartment E to compartment I ,and individuals entering compartment I spend,on average,1=d time units there.Although conditions (A1)–(A5)do not restrict the decomposition of f i ðx Þto a single choice for F i ,only one such choice is epidemiologically correct.Different choices for the function F lead to different values for the spectral radius of FV À1,as shown in Table 1.In column (a),treatment failure is considered to be a new infection and in column (b),both treatment failure and pro-gression to infectiousness are considered new infections.In each case the condition q ðFV À1Þ<1yields the same portion of parameter space.Thus,q ðFV À1Þis a threshold parameter in both cases.The difference between the numbers lies in the epidemiological interpretation rather than the mathematical analysis.For example,in column (a),the infection rate is b 1þpr 2and an exposed individual is expected to spend m =ððd þm þr 1Þðd þr 2ÞÞtime units in compartment I .However,this reasoning is biologically flawed since treatment failure does not give rise to a newly infected individual.Table 1Decomposition of f leading to alternative thresholds(a)(b)Fb 1SI =N þb 2TI =N þpr 2I 0000B B @1C C A b 1SI =N þb 2TI =N þpr 2I m E 000B B @1C C A Vðd þm þr 1ÞE Àm E þðd þr 2ÞI Àb ðN ÞþdS þb 1SI =N dT Àr 1E Àqr 2I þb 2TI =N 0B B @1C C A ðd þm þr 1ÞE ðd þr 2ÞI Àb ðN ÞþdS þb 1SI =N dT Àr 1E Àqr 2I þb 2TI =N 0B B @1C C A F0b 1þpr 200 0b 1þpr 2m 0 V d þm þr 10Àm d þr 2d þm þr 100d þr 2 q (FV À1)b 1m þpr 2mðd þm þr 1Þðd þr 2Þffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffib 1m þpr 2mðd þm þr 1Þðd þr 2Þs 36P.van den Driessche,J.Watmough /Mathematical Biosciences 180(2002)29–484.2.Multigroup modelIn the epidemiological literature,the term‘multigroup’usually refers to the division of a het-erogeneous population into several homogeneous groups based on individual behaviour(e.g., [14]).Each group is then subdivided into epidemiological compartments.The majority of mul-tigroup models in the literature are used for sexually transmitted diseases,such as HIV/AIDS or gonorrhea,where behaviour is an important factor in the probability of contracting the disease [7,8,14,15].As an example,we use an m-group SIRS-vaccination model of Hethcote[7,14]with a generalized incidence term.The sample model includes several SI multigroup models of HIV/ AIDS as special cases[8,15].The model equations are as follows:_I i ¼X mj¼1b ijðxÞS i I jÀðd iþc iþ iÞI i;ð7aÞ_S i ¼ð1Àp iÞb iÀðd iþh iÞS iþr i R iÀX mj¼1b ijðxÞS i I j;ð7bÞ_Ri¼p i b iþc i I iþh i S iÀðd iþr iÞR i;ð7cÞfor i¼1;...;m,where x¼ðI1;...;I m;S1;...;S m;R1;...;R mÞt.Susceptible and removed individu-als die at the rate d i>0,whereas infected individuals die at the faster rate d iþ i.Infected in-dividuals recover with temporary immunity from re-infection at the rate c i,and immunity lasts an expected1=r i time units.All newborns are susceptible,and a constant fraction b i are born into each group.A fraction p i of newborns are vaccinated at birth.Thereafter,susceptible individuals are vaccinated at the rate h i.The incidence,b ijðxÞdepends on individual behaviour,which determines the amount of mixing between the different groups(see,e.g.,Jacquez et al.[16]). The DFE for this model isx0¼ð0;...;0;S01;...;S0m;R01;...;R0mÞt;whereS0 i ¼b i d ið1Àp iÞþr iðÞd iðd iþh iþr iÞ;R0 i ¼b iðh iþd i p iÞd iðd iþh iþr iÞ:Linearizing(7a)about x¼x0givesF¼S0i b ijðx0ÞÂÃandV¼½ðd iþc iþ iÞd ij ;where d ij is one if i¼j,but zero otherwise.Thus,FVÀ1¼S0i b ijðx0Þ=ðd iÂþc iþ iÞÃ:P.van den Driessche,J.Watmough/Mathematical Biosciences180(2002)29–4837For the special case with b ij separable,that is,b ijðxÞ¼a iðxÞk jðxÞ,F has rank one,and the basic reproduction number isR0¼X mi¼1S0ia iðx0Þk iðx0Þd iþc iþ i:ð8ÞThat is,the basic reproduction number of the disease is the sum of the‘reproduction numbers’for each group.4.3.Staged progression modelThe staged progression model[11,Section3and Appendix B]has a single uninfected com-partment,and infected individuals progress through several stages of the disease with changing infectivity.The model is applicable to many diseases,particularly HIV/AIDS,where transmission probabilities vary as the viral load in an infected individual changes.The model equations are as follows(see Fig.2):_I 1¼X mÀ1k¼1b k SI k=NÀðm1þd1ÞI1;ð9aÞ_Ii¼m iÀ1I iÀ1Àðm iþd iÞI i;i¼2;...;mÀ1;ð9bÞ_Im¼m mÀ1I mÀ1Àd m I m;ð9cÞ_S¼bÀbSÀX mÀ1k¼1b k SI k=N:ð9dÞThe model assumes standard incidence,death rates d i>0in each infectious stage,and thefinal stage has a zero infectivity due to morbidity.Infected individuals spend,on average,1=m i time units in stage i.The unique DFE has I i¼0,i¼1;...;m and S¼1.For simplicity,define m m¼0. Then F¼½F ij and V¼½V ij ,whereF ij¼b j i¼1;j6mÀ1;0otherwise;&ð10ÞV ij¼m iþd i j¼i;Àm j i¼1þj;0otherwise:8<:ð11ÞLet a ij be the(i;j)entry of VÀ1.Thena ij¼0i<j;1=ðm iþd iÞi¼j;Q iÀ1k¼jm kQ ik¼jðm kþd kÞj<i:8>>><>>>:ð12ÞThus,R0¼b1m1þd1þb2m1ðm1þd1Þðm2þd2Þþb3m1m2ðm1þd1Þðm2þd2Þðm3þd3ÞþÁÁÁþb mÀ1m1...m mÀ2ðm1þd1Þ...ðm mÀ1þd mÀ1Þ:ð13ÞThe i th term in R0represents the number of new infections produced by a typical individual during the time it spends in the i th infectious stage.More specifically,m iÀ1=ðm iÀ1þd iÀ1Þis the fraction of individuals reaching stage iÀ1that progress to stage i,and1=ðm iþd iÞis the average time an individual entering stage i spends in stage i.Hence,the i th term in R0is the product of the infectivity of individuals in stage i,the fraction of initially infected individuals surviving at least to stage i,and the average infectious period of an individual in stage i.4.4.Multistrain modelThe recent emergence of resistant viral and bacterial strains,and the effect of treatment on their proliferation is becoming increasingly important[12,13].One framework for studying such sys-tems is the multistrain model shown in Fig.3,which is a caricature of the more detailed treatment model of Castillo-Chavez and Feng[12,Section2]for tuberculosis and the coupled two-strain vector–host model of Feng and Velasco-Hern a ndez[17]for Dengue fever.The model has only a single susceptible compartment,but has two infectious compartments corresponding to the two infectious agents.Each strain is modelled as a simple SIS system.However,strain one may ‘super-infect’an individual infected with strain two,giving rise to a new infection incompartment。

不同剂量天麻素对甲基苯丙胺依赖大鼠条件位置偏爱及海马小胶质细胞激活的影响

不同剂量天麻素对甲基苯丙胺依赖大鼠条件位置偏爱及海马小胶质细胞激活的影响

昆明医科大学学报2021,42(5):6-11 Journal of Kunming Medical University DOI:10.12259/j.issn.2095-610X.S2*******CN53-1221/R不同剂量天麻素对甲基苯丙胺依赖大鼠条件位置偏爱及海马小胶质细胞激活的影响朱婷娜°,刘鹏亮",董文娟2),于浩2),吴亚梅D,黄兆奎D,洪仕君2),赵永娜⑶(1)昆明医科大学药学院暨云南省天然药物药理重点实验室;2)法医学院;3)国际教育学院,云南昆明650500)[摘要]目的研究不同剂量天麻素(gastrodin,Gas)对甲基苯丙胺(methamphetamine,Meth)依赖大鼠条件性位置偏爱(conditioned place preference,CPP)的影响及海马小胶质细胞激活状态的改变。

方法腹腔注射Meth(10mg/kg,qd,14d)建立Meth依赖大鼠CPP模型,然后采用10mg/kg、30mg/kg、100mg/kg不同剂量的天麻素治疗14d,测定不同剂量天麻素对Meth依赖大鼠CPP效应的影响;用免疫荧光技术检测不同剂量天麻素对海马小胶质细胞激活的影响。

结果Meth依赖大鼠CPP模型建立成功。

与生理盐水组相比,Meth组的CPP效应明显增强,差异有统计学意义(P<0.05);天麻素治疗可使大鼠在伴药箱停留时间明显缩短;与Meth 组相比,10mg/kg、30mg/kg、100mg/kg的天麻素治疗后,可呈剂量依赖性地降低Meth诱导的CPP效应,且100mg/kg的天麻素可基本消除Meth诱导的CPP效应。

免疫荧光检测结果显示,与生理盐水组相比,Meth组大鼠海马小胶质细胞明显被激活;经10mg/kg、30mg/kg、100mg/kg的天麻素治疗后,小胶质细胞激活被明显抑制,且30mg/kg、100mg/kg两组剂量的天麻素治疗后抑制效果更明显。

毕赤酵母手册

毕赤酵母手册
pPICZ A, B, and C
Pichia expression vectors for selection on Zeocin™ and purification of secreted, recombinant proteins
Cat. no. V195-20 Rev. Date: 7 July 2010 Manual part no. 25-0150
MAN0000035
User Manual
ii
Table of Contents
Important Information................................................................................................................................ v Accessory Products ................................................................................................................................... vii Introduction ................................................................................................................................................. 1 Overview .......................................................................................................................................................1 Methods........................................................................................................................................................ 2 Cloning into pPICZ A, B, and C...............................................................................................................2 Multiple Cloning Site of pPICZ A ...........................................................................................................5 Multiple Cloning Site of pPICZ B ............................................................................................................6 Multiple Cloning Site of pPICZ C............................................................................................................7 Pichia Transformation ..................................................................................................................................9 Expression in Pichia ....................................................................................................................................13 Purification ...........................................................................................................................15 Appendix .................................................................................................................................................... 17 Recipes .........................................................................................................................................................17 Zeocin™ ........................................................................................................................................................19 pPICZ Vector ............................................................................................................................................21 Lithium Chloride Transformation Method.............................................................................................23 Construction of In Vitro Multimers..........................................................................................................25 Technical Support.......................................................................................................................................33 Purchaser Notification ...............................................................................................................................34 References....................................................................................................................................................35

ICH术语表

ICH术语表

ICH领域专业术语表(质量、安全性)序号英文中文1"relevant" viruses and "model" viruses“相关”病毒和“模型”病毒225-fold AUC radio25倍的AUC比值3 a single 2 generation study单项包括两代(生殖毒性)的研究4abbreviated or abridged application简略申请5abnormal karyology异常核形6abortions流产7absorbed moisture吸附水8absorption吸收9acceptable daily intake可接受的日摄入量10acceptable test加速试验11acceptance criteia认可标准12accuracy准确性13accuracy准确度14acelerated/stress stability studies加速/强力破坏稳定性研究15acentric fragment无着丝点片段16acetylation 乙酰化作用17achiral assay非手性测定18achlorhydric eldderly老年性胃酸缺乏症19acridine orange吖啶橙20action limits内控限值21active components/compound/moiety活性成分22active ingredient活性组分23active metabolite活性代谢产物24adaption to specific culture conditions特定培养条件的适应25additional test 附加实验26additions添加剂27adduct加合物28adequate exposure充分暴露29adjuvant 佐剂30ADME吸收、分布、代谢、排泄31administration period给药期32adventitious agents外源性因子33adventitious contaminants外来污染物34adventitious viral or mycoplasma contamination外源性病毒或支原体污染35adventitious viruses外源病毒36advers effect不良反应37adverse reaction不良反应38aerobic microorganisms需氧微生物39affinity亲和力40affinity chromatography亲和层析41affinity column亲和柱42against humanised proteins serum antibodies抗人源蛋白血清抗体 43agar and broth琼脂和肉汤44aggregates 聚合体45aggregation聚集46aginal smear阴道涂片 47air ighting reflex空中翻正反射48alkylating electrophilic center烷化亲电子中心49allele基因突变产生的遗传因子50allergenic/allergic extracts过敏原抽提物51allergic reactions过敏性反应(变应性反应)52altenative validated test有效替代试验53altered conjugated forms改变的结合物形式54altered growth 生长改变55ambient condition自然条件56amino acid composition氨基酸组成57amino acid sequence氨基酸顺序58amino acids氨基酸59amino sugars氨基糖60amino-terminal amino acids氨基端氨基酸61ammonia production Rates产氨率62ammoniun sulphide staining of the uterus子宫硫化胺染色 63analogue类似物(同系物)64analogue series of substances同系物65analyte 被测物66analytical method 分析方法67analytical procedure分析方法68anaphase分裂后期69aneuploidy非整倍体70aneuploidy inducer非整倍体诱导剂71animal cell lines动物细胞系72animal tissues or organs动物组织或器官73antennary profile 触角形状74antibiotic resistance genes抗生素耐药基因75antibiotics抗生素76antibody抗体77antibody production tests抗体产生试验78antigenic specificity抗原特异性79antisera抗血清80apoptosis凋亡81applicant申报者82art and ethical standards技术和伦理标准83ascites腹水84assay含量测定85assay procedure定量方法86assessment of genotoxicity遗传毒性评价87attainment of full sexual function达到性成熟 88AUC曲线下面积89auditory startle relex惊愕反射(听觉惊跳反射)90autoimmune自身免疫91autoradiographic assessment放射自显影评价92autoradiography放射自显影93avian鸟类94avidity亲和性95background 背景96bacteria细菌97bacterial mutagenicity test细菌致变突试验98bacterial reverse mutation test细菌回复突变试验99bacterial strains菌株100bacterial test organisms微生物试验菌101base pairs碱基对102base set of strains基本菌株103base substitution碱基置换104batches批次105batch-to-batch逐批106between-assay variation试验间变异107binary fission双数分裂108binding assays结合试验109bioanalytical method生物学分析方法110bioavaiability生物利用度111bioburden生长量/生物负荷112biochemical methods生化方法113bioequivalency生物等效性114biohazard enformation生物有害信息115biological activity生物活性116biological products生物制品117biological relevance生物学意义118bioreactor生物反应器119biotechnological products生物技术产品120biotechnological/biological products生物技术/生物制品121biotechnology-derived pharmaceuticals生物技术药物122biphasic curve双相曲线123birth出生124blood plasma factors血浆因子125body burden机体负担126body fluids体液127bone marrow cell骨髓细胞128bouin's fixation包氏液固定129bovine牛130bovine spongiform encephalopathy(BSE)疯牛病131bracketing括号法132breakage of chromatid染色单体断裂133breakage of chromosome染色体断裂134breeding conditions饲养条件135bridging character桥梁作用136by-products副产物137C(time)一定剂量、某一时间的浓度138calibrate标化139canine犬140cap liner瓶帽内垫141capillary electrophoresis毛细管电泳142carbohydrate碳水化合物143carboxy-terminal amino acids羧基端氨基酸144carcinogen致癌物质145carcinogenesis致癌性146carcinogenic hazard致癌性危害147carcinogenicity bioassay致癌性生物检测148carcinogenicity potential of chemical化合物的潜在致癌性149carcinoginicity(oncogenicity)致癌(致瘤)150cardiovascular心血管151carrier载体/担体152case-by-case个例153catalysts催化剂154cell bank 细胞库155cell bank system细胞库系统156cell banking procedures细胞建库过程157cell banking system细胞库系统158cell culture-derived impurities来源于细胞培养基的杂质159cell cultures 细胞培养物160cell cultures 细胞培养161cell expansion细胞扩增162cell fusion细胞融合163cell line细胞系164cell lines 细胞系165cell membrane lipid细胞膜脂质层166cell metabolites细胞代谢物167cell pooling细胞混合168cell proliferation细胞增植169cell replication system细胞复制系统170cell substrate-derived impurities 来源于细胞基质的杂质171cell substrates细胞基质172cell suspension细胞悬液173cell viability细胞活力174cell-derived biological products细胞来源的生物制品175cell-mediated immunity细胞介导的免疫176cellular blood components血细胞成分177cellular therapy细胞治疗178cemadsorbing viruses红细胞吸附病毒179central nervous systems中枢神经系统180cerbral spinal fluid脑脊液181characterization and testing of cell banks细胞库鉴定及检测182charcoal活性炭183charge电荷184chemical actionmertric system化学光化线强度系统185chemical nature化学性质186chemical reactivity 化学反应性187chemical syntheses化学合成188chemically inert化学惰性189chewable tablets咀嚼片190childbeering potential生育可能性191chinese hamster V79 cell中国仓鼠V79细胞192chiral impurities手性杂质193CHL cell中国仓鼠肺细胞194CHO cell中国仓鼠卵巢细胞195chromatide染色单体196chromatograms色谱图197chromatographic behavior色谱行为198chromatographic procedures色谱方法199chromatography columns色谱分离柱200chromosomal aberration染色体畸变201chromosomal damage染色体损伤202chromosomal integrity染色体完整性203chronic toxicity testing 慢性毒性试验204circular dichroism圆二色性205classfical biotransformation studies经典的生物转化试验206clastogen染色体断裂剂207clastogenic致染色体断裂的208clearance studies清除研究209cleavage of the balanopreputial gland 龟头包皮腺裂开210climatic zones气候带211clinical indication临床适应证212clinical research临床研究213clinical trial application 临床试验申请214clisure闭塞物215cloning 克隆216cloning efficiency克隆形成率217closure of hard palate硬腭闭合218C max峰浓度219coat growth毛发生长220code number编号221coding sequence编码序列222coefficient of variance变异系数223collaborative studies协作实验研究224colony isolation菌落分离225colony sizing集落大小226colony-stimulating factors集落刺激因子227combination product复方制剂228comparative trial对比试验229complement binding补体结合230completely novel compound全新化合物231components成分232compound bearing stuctural alerts结构可疑化合物233concentration threshold阈浓度234conception受孕235concomitant toxicokinetics相伴毒代动力学236confidence interval置信区间237confidence limits可信限238confirmatory studies确认研究239conformance to specifcations符合规范240conformation构型241conjugated product连接产物242conjugation连接243consistency一致性244container容器245container/closure容器/闭塞物246container/closure integrity testing 容器/密封完整性试验247contaminants污染物248contaminated cell substrate污染的细胞基质249content uniformity含量均匀度250continuous treatment 连续接触251control methodology控制方法学252controlled released product控释制剂253conventional live virus vaccines传统的活病毒疫苗254conventional vaccines传统疫苗255cool white fluorescent冷白荧光灯256corpora lutea黄体257corpora lutea count黄体数258correction factor校正因子259correlation coefficient相关系数260covalent or noncovalent共价或非共价261creams霜剂262cross-contamination交叉污染263cross-linking agent交联剂264cross-reactivity交叉反应265cryopreservation冷冻保存266cryoprotectants防冻剂267crystals晶体268culture components 培养基成分269culture condiction培养条件270culture confluency培养克隆率271culture confluenty培养融合272culture media/medium培养基273culture medium培养基274cyanogen bromide溴化氰275cytogenetic细胞遗传学的276cytogenetic change细胞遗传学改变277cytogenetic evaluation细胞遗传学评价278cytokines细胞因子279cytopathic细胞病的280cytoplasmic A-and R-type particles细胞浆a型和r型颗粒281cytotoxicity细胞毒282dark control暗度控制283dead offspring at birth 出生时死亡的子代284deamidation去氨基285deaminated去酰胺化的286deamination脱氨基287decision flow chart/tree判断图288definable and measurable biological activity明确和可测定的生物学活性289degradant降解产物290degradation降解291degradation pathway降解途径292degradation product降解产物293degradation profile降解概况294degree of aggregation 凝集度295degree of scatter离散程度296delay of parturition分娩延迟297delayed-release延迟释放298deleterious有害的299deletion缺失300delivery systems给药体系301derivatives衍生物302description 性状303descriptive statistics描述性统计304detection limit检测限度305detection of bacterial mutagen细菌诱变剂检测306detection of clastogen染色体断裂剂检测307determination of metabolites测定代谢产物308development of the offspring 子代发育309developmental toxicity发育毒性310dilivery systems释放系统311dilution ratio释放倍数312dimers二聚体313diminution of the background lawn背景减少314diode array二极管阵列315diploid cells二倍体细胞316direct genetic damage 直接遗传损伤317dissociation解离318dissolution testing溶出试验319dissolution time溶出时间320distribution分布321DNA adduct DNA加合物322DNA damage DNA损伤323DNA repair DNA修复324DNA strand breaks DNA链断裂325dosage form剂型326dose dependence剂量依赖关系327dose escalation剂量递增328dose level剂量水平329dose -liming toxicity剂量限制性毒性330dose-ranging studies剂量范围研究331dose-related剂量相关 332dose-relatived cytotoxicity剂量相关性细胞毒性333dose-relatived genotoxic activity剂量相关性遗传毒性334dose-relatived mutagenicity剂量相关性诱变性335dose-response curve剂量-反应曲线336dosing route给药途径337downstream purification下游纯化338drug product制剂339drug product components制剂组方340drug substances原料药341duration周期342duration of pregnancy妊娠周期343eaning断奶344earlier physical malformation早期身体畸形345early embryonic development早期胚胎发育346early embryonic development to implantation着床早期的胚胎发育347ectromelia virus脱脚病病毒348elastomeric closures橡皮塞349electro ejaculation电射精350electron microscopy(EM)电镜351electrophoresis电泳352electrophoretic pattern电泳图谱353elimination消除354elution profile洗脱方案355embryofetal deaths胚胎和胎仔死亡356embryo-fetal development 胚胎-胎仔发育357embryo-fetal toxicity胚胎-胎仔毒性358embryonated eggs鸡胚359embryonic death胚胎死亡360embryonic development胚胎发育361embryonic period胚胎期362embryos胚胎 363embryotoxicity胚胎毒性364enantiomer对映体365enantiomer对映异构体366enantiomeric镜像异构体367enantioselective对映体选择性368encephalomyocarditis virus(EMC)脑心肌炎病毒369end of pregnancy怀孕终止370endocytic 内吞噬(胞饮)371endocytic activity内吞噬活性372endogenous agents内源性因子373endogenous components内源性物质374endogenous gene内源性基因375endogenous proteins内源性蛋白376endogenous retrovirus内源性逆转录病毒377endonuclease核酸内切酶378endonuclease release form lysosomes溶酶体释放核酸内切酶379endotoxins内毒素380end-point终点381end-product sterility test-ing最终产品的无菌试验382enhancers增强子383enveloped RNA viruses包膜RNA病毒384environmental factors环境因素385enzymatic reaction rates酶反应速率386enzyme酶387epididymal sperm maturation附睾精子成熟性388epitope表位389epitope抗原决定部位390Epstein-Barr virus (EBV)EB病毒391equine马392error prone repair易错性修复393erythropoietins促红细胞生成素394escalation递增395escherichia coli starn大肠杆菌菌株396esscherichia coli 大肠杆菌397ethnic origin种族起源398eukaryotic cell真核细胞399evaluation of test result试验结果评价400ex vivo体外401exaggerated pharmacological response超常增强的药理作用402excipient赋形剂403excipient specifications赋形剂规范404excretion排泄(消除)405expiration date/dating失效日期406exposure assessment 接触剂量评价407exposure level暴露程度408exposure period光照时间409exposure period接触期410expression constract表达构建体411expression system表达系统412expression vector表达载体413extended-release延时释放414extent of the virus test病毒测试的程度415external metabolising system体外代谢系统416extinction coefficient消光系数417extrachromosomal染色体外418extraneous contaminants外源性污染物419extrapolation 外推法420F1-animals子一代动物421false negative result假阴性结果422false positive result假阳性结果423fecundity多产424feed-back反馈425fermentation发酵426fermentation products发酵产品427fertilisation受精428fertility生育力429fertility studies生育力研究430fetal abnormalities胎仔异常431fetal and neonatal parameters胎仔和仔鼠的生长发育参数432fetal development and growth胎仔发育和生长433fetal period 胎仔期434fetotoxicity胎仔毒性435fill volume装量436filter aids 过滤介质437final manufacturing最终生产438finished product成品439first pass testing 一期试验440flanking region侧翼区441fluorescence in situ hybridisation (FISH)原位荧光分子杂文442foetuses胎仔443forced degradation testing强制降解试验444foreign matter异质性物质445formal labeling正式标签446formal stability studies正式的稳定性研究447formulation 处方/配方448formulation 制剂449fragmentation片段化450frameshift mutation移码突变451frameshift point mutation移码点突变452free-standing独立453freeze-dried product冻干产品454fresh dissection technique新鲜切片技术455friability脆碎度456functional deficits功能试验457functional test功能性指标458funetional indices融合蛋白459fungi真菌460fusion partners融合伴侣461fusion protein融合蛋白462fusion proteins配子463gametes动物性别464gel filtration 凝胶过滤465gender of animals性别专一性药物466gender-specific drug基因剔除467gene amplification基因扩增468gene knockout基因治疗469gene mutation基因突变470gene therapy基因疗法471generation of the cell substrate细胞基质的产生472genetic遗传473genetic change 遗传学改变474genetic damage遗传学损伤475genetic endpoint遗传终点476genetic manipulation基因操作477genetic toxicity遗传毒性478genomic dinucleotide repeats基因组双核苷酸重复数479genomic DNA基因组DNA480genomic polymorphism pattern基因组形态类型481genotoxic activity遗传毒性作用482genotoxic carcinogen遗传毒性致癌剂483genotoxic effect 遗传毒性效应484genotoxic hazard遗传毒性危害485genotoxic potential潜在遗传毒性486genotoxic rodent carcinogen啮齿类动物遗传毒性致癌剂487genotoxicity 遗传毒性488genotoxicity evaluation遗传毒性评价489genotoxicity test遗传毒性试验490genotoxicity test battery遗传毒性试验组合491genotypic 基因型492germ cell mutagen生殖细胞诱变剂493germ line mutation生殖系统突变494GLP临床前研究质量管理规范495glucose consumption rates耗糖率496glycoforms糖化形式497glycosylation糖基化498goegrapgical origin 地理起源499gross chromosomal damage 染色体大损伤500gross evaluation of placenta 胎盘的大体评价501growth factors生长因子502growth hormones 生长激素503guanidine胍504haematoxylin staining苏木素染色505half-life半衰期506hamster antibody production(HAP) test仓鼠抗体产生实验507Hantaan virus汉坦病毒508hardness硬度509heavy metals重金属510hematopoietic cells造血细胞511heparins肝素512heptachlor七氯化合物513herbal products草药514heritable遗传515heritable defect遗传缺陷516heritable disease遗传性疾病517heritable effect 遗传效应518herpes virus 疱疹病毒519heterogeneities异质性520heterohybrid cell lines异种杂交细胞系521high concentration高浓度522high-resolution chromatography高分辨色谱523histologic appearance of reproductive organ生殖器官的组织学表现524histopathological chang组织病理学改变525homogeneity均一性526homologous proteins同系蛋白527homologous series同系528host cell 宿主细胞529host cell banks宿主细胞库530host cell DNA宿主细胞DNA531host cell proteins宿主细胞蛋白质532hot-stage microscopy热价显微镜533human carcinogen人类致癌剂534human cell lines人细胞系535human diploid fibroblasts人二倍体成纤维细胞536human lymphoblastoid TK6 cell 人成淋巴TK6细胞537human mutagen人类致突变剂538human polio virus人脊髓灰质炎病毒539human subjects人体540human tropism人向性541humidity湿度542humidity-protecting containers防湿容器543humoral immunity 体液免疫544hybridization techniques杂交技术545hybridoma cell杂交瘤细胞546hybridomas杂交瘤547hydrolysates水解物548hydrolytic enzymes水解酶549hydrophobicity疏水性550hygroscopic吸湿性551identification/identity鉴别552immature erythrocyte未成熟红细胞553immediate and latent effect速发和迟发效应554immediate container/closure直接接触的容器/密闭物555immediate pack内包装556immediate release立即释放557immortalization激活558immune spleen cells免疫脾细胞559immunoassay免疫检测560immunochemical methods免疫化学方法561immunochemical properties免疫化学性质562immunoelectrophoresis免疫电泳563immunogenicity免疫原性564immunological interations免疫相互作用565immunopathological effects免疫病理反应566immunoreactivity免疫反应性567immunotoxicity免疫毒性568implantation着床569implantation sites着床部位570impurity profile杂质概况571in vitro体外572in vitro and in vivo inoculation tests体内和体外接种试验573in vitro assay体外检测574in vitro cell age体外细胞传代期575in vitro lifespan体外生命周期576in vitro test体外试验577in vitro tests体外试验578in vitro/in vivo correlation体内体外相关性579in vivo体内580in vivo assays体内检测581in vivo test体内试验582inactivated vaccine 灭活疫苗583incidence of polyploid cell 多倍体细胞发生率584incisor eruption门齿萌出585independent test独立试验586indicator cell指示细胞587indicator organisms指示菌588individual fetal body weight单个胎仔体重589indoor indirect daylight室内间接日光590induced and spontaneous models of disease诱发或自发的疾病模型591inducer of micronuclei微核诱导剂592inducers 诱导剂593inedntification test鉴别试验594infectious agents感染性因子595influenza virus流感病毒596inhalation吸入597inhalation dosage forms 吸入剂型598inhibitor of DNA metabolism DNA代谢抑制剂599in-house内部的600in-house criterea内控标准601in-house primary reference material内部一级参比物质602in-house reference materials内部参比物质603in-house working reference material内部工作参比物质604initial filing原始文件605initial submission最初申报606initial text最初文本607inoculation接种608inorganic impurities无机杂质609inorganic mineral无机矿物质610inorganic salts无机盐611in-process acceptance criteia生产过程认可标准612in-process controls生产过程中控制613in-process testing生产过程中检测614insect昆虫615insulins胰岛素616intact animals完整动物(整体动物)617intake摄入618intended effect预期效果619intended storage period 预期的贮藏期620intentional degradation人为降解621interactions相互作用622interferon干扰素623interleukins白细胞介素624intermediate中间体625intermediate precision中间精密度626intermediates半成品627internal control内对照628international reference standards国际参比标准品629interphase muclei分裂间期细胞核630intra-and inter-individual个体与个体间631intra-assay precision间隙含量精密度632intracytoplasmic细胞浆内633introduction of virus病毒介入634inverted or horizontal position倒立或水平位置635ion-exchange离子交换636ionic content离子含量637isoelectric focusing/isoelectrofocusing等电聚焦638isoenzyme analysis同工酶分析639isoform pattern异构体类型640isolated organs离体器官641isomerized 异构化的642Jp/Ph.Eur./Usp.日本药局方/欧洲药典/美国药典643juvenile animal studies未成年动物研究644K virus K病毒645karyology胞核学646Kinetic profile动力学特点647Kinetics 动力学648laboratory scale实验室规模649lactate production rates乳糖产生速率650Lactating授乳、哺乳651lactic dehydrogenase virus (LDM)乳酸脱氢酶病毒652Large deletion event大缺失事件653Late embryo loss后期胚胎丢失654leachables沥出物655Level of safety安全水平656Libido性欲657Life threatering危及生命658ligand 配位体/配体659light光照660light resistant packaging避光包装661limit for in vitro cell age 细胞体外传代限度662limit of acceptance可接受的限度663limit of in vitro cell age 体外细胞代次664limit test限度试验665limulus amoebocyte lysate鲎试剂666linear relation ship 线性关系667linearity线性668Lipophilic compound亲脂性化合物669liquid nitrogen 液氮670liquid oral dosage forms 液体口服制剂671Litter size每窝胎仔数目672Live and dead conceptuese活胎和死胎673Live offspring at birth出生时存活的子代674live vaccine 活疫苗675living cells活细胞676Local toxicity局部毒性677Lockl tolerance studies 局部耐受性研究678Locu位点679logarithmic scale:对数级680long term test长期试验681Long-term carcinogenicity study长期致癌性试验682long-time and accelerated stability长期和加速稳定性试验683Loss of the tk gene tk 基因丢失684losses of activity活性丧失685lot release 批签发686low molecular weight subsances低分子量物质687lower-observed effect level (LOEL)能观察到反应的最低量688lymphocytic choriomeningitis virus (LCM)淋巴细胞性脉络丛脑膜炎病毒689lyophilised cakes冻干粉饼690lysate of cells 细胞溶解物691Major organ fomeation主要器官形成692Male fertility雄性生育力693Male fertility assessment雄性生育力评价694mammalian哺乳类695Mammalian cell mutation test哺乳动物细胞致突变试验696Mammalian cells哺乳动物细胞697Mammalian species哺乳类动物698manufacturing scale生产规模699marieting pack 上市包装700marker chromosome 标志染色体701marketing approval批准上市702Marketing approval上市许可703mass 重量704mass balance质量平衡705mass spectrometry质谱706master cell bank (MCB)主细胞库707Matemal animal亲代动物708material balance物质平衡709Mating behaviour交配行为710Mating period交配期711Mating ratio交配比例712Matrices基质713matrix基质、矩阵714matrix system矩阵化设计715matrixing每日最大剂量716maximum daily dose平均动力学温度717Maximum tolerated dese(MTD)最大耐受剂量718mean kinetic temperature后生动物细胞培养719Mechanism of genotoxicity遗传毒性机制720Mechanistic activation代谢活化721Mechanistic activation pathway代谢活化途径722Mechanistic activation system代谢活化系统723Mechanistic investigation机制研究724Metabolism代谢725Metabolites profile代谢物的概况726Metaphase中期727Metaphase analysis分裂中期相分析728Metaphase cell分裂中期细胞729metazoan cell culture微生物细胞培养730microbial cells微生物细胞731microbial contamunation 微生物污染732microbial expression system微生物表达系统733microbial limits微生物限度734microbial metabolites微生物代谢物735microbial proteases微生物蛋白酶736microbial vaccine antigens微生物疫苗抗原737microbiological testing 微生物学试验738Micronucleus微核739Micronucleus formation微核形成740Microtitre微滴定741Microtitre method微滴定法742Mimicking模拟743minimum exposure time最低作用时间744minimum of pilot plant试产规模745minute virus of mice小鼠小病毒746mirror image 镜像747mismached S-S linked错连的S-S键748Mitotic index有丝分裂指数749modified-/modifying release修饰释放750modifying factor修正因子751moisture level水分752molar absorptivity克分子吸收753Molecular characterisation分子特性754molecular characteristics分子特性755molecular confirmation分子构型756molecular entities/entity分子实体757molecular size分子大小758Molecular technique分子技术759Monitor监测760Monoclonal antibodies单克隆抗体761monoclonal antibody单克隆抗体762mork run空白对照试验763morphological analysis形态学分析764mouse antibody production (MAP) test小鼠抗体产生试验765mouse cytomegalovirus (MCMV)小鼠巨细胞病毒766mouse encephalomyelitis virus (GDVII)小鼠脑脊髓炎病毒767mouse hepatitis virus (MHV)小鼠肝炎病毒768Mouse lymphoma tk assay小鼠淋巴瘤tk检测769Mouse lymphoma L5178Y cell小鼠淋巴瘤L5178Y细胞770mouse rotavirus (EDIM)小鼠小轮状病毒771MuLV murine leukemia virus鼠白血病病毒772murine hybridoma cell lines鼠杂交瘤细胞系773Mutagen诱变原774Mutagen carcinogen诱变性致癌剂775Mutagen potential of chemical化合物的潜在致突变性776Mutant colony突变体集落777Mutation突变778Mutation induction in transgenes转基因诱导突变779mutations 突变780mycoplasma支原体781myeloma cell line骨髓瘤细胞系782Naked eye肉眼783national or international reference material国家或国际参比物质784national reference standards国家参比标准品785near ultraviolet lamp近紫外灯786Necropsy(macroscopic examination)解剖(大体检查)787Negative control阴性对照788Negative result阴性结果789Neonate adaptation to extrautenrine life新生仔宫外生活的适应性790neural sugars中性糖791new chemical entity新化学体792new dosage form新剂型793new drug products/produce新药制剂794new drug substance新原料药795new molecular entities新分子体796Newbom新生仔797Newcleated有核798no effect level不产生反应的量799Non rodent非啮齿类800Non-clinical非临床801noncovalent/convalent forces非共价/共价键802non-enveloped viruses非包膜病毒803Non-genotoxic carcinogen非遗传毒性致癌剂804Non-genotoxic mechanism非遗传毒性机制805Non-human primate非人灵长类806Non-linear非线性807non-mammalian animal cell lines非哺乳动物细胞系808non-recombinant cell-cul-ture expression systems非重组细胞培养表达系统809non-recombinant products/vaccines非重组制品/疫苗810non-specific model virus非特异模型病毒811Non-toxic compound无毒化合物812Non-toxic-effect dose level无毒性反应剂量水平813no-observed effect level不能观察到反应的量814N-terminal sequencing N端测序815nuclear magnetic resonance 核磁共振816Nucleated bone marrow cell有核骨髓细胞817nucleic acid核酸818Nucleoside analogue核苷酸同系物819nucleotide sequences 核苷酸序列820Number of live and dead implantation宫内活胎和死胎数821Numerical chromosmal aberration染色体数目畸变822Numerical chromosome changes染色体数目改变823Oestrous cycle动情周期824official procedure正式方法825ointments软膏826oligonucleotide低聚核苷酸827Oligonucleotide grugs寡核苷酸药物828oligosaccharide pattern寡糖类型829One,two,three generation studies一、二、三子代研究830opacity浊度831Organ development器官发育832organic impurities有机杂质833origins of replication复制起点834osmolality摩尔渗透压浓度835outdoor daylight室外日光836Ovulation rate排卵率837oxidation氧化838oxygen consumption rates耗氧量839package包装840Paraffine embedding石蜡包埋841parainfluenza virus副流感病毒842parallel control assays 平行对照分析843Parameter参数844Parent compound母体化合物845parent stability Guideline稳定性试验总指导原则846parental cell line母细胞系847Parenteral非肠道848parenterals非肠道制剂849particle size粒度850Particulate material颗粒物851particulate matter微粒852Parturition分娩延迟853parvoviruses细小病毒854passage history of the cell line细胞系的传代史855pathogenic agents致病因子856pathogenicity致病性857patterns of degradation降解方式858Pediatric populations小儿人群859peptide肽860peptide map 肽图861percent recovery回收率862periodic/skip testing定期检验/抽验863Peripheral blood erythrocyte外周血红细胞864permitted daily exposure允许的日接触量865Perpoductive competence生殖能力866phage typing噬菌体分型867pharcodynamic studies药效学研究868Pharmacodinetic药代动力学869Pharmacodynamic effects药效作用870Pharmacodynamics药效学(药效动力学)871pharmacopoeial药典872pharmacopoeial pharmacoppeial specifications药典规范873pharmacopoeial standards药典标准874phenotypic 表型875Phenylene diamine苯二胺876phosphorylation磷酸化作用877photostability testing光稳定性试验878Physical development身体发育879physicochemical changes理化改变880physicochemical methods物理化学方法881physico-chemical properties物理化学特性882Physiological stress生理应激883Pilot studies 前期研究884pilot-plant scale试生产规模/中试规模885Pinna unfolding耳廓张开886piston release force活塞释放力887piston travel force活塞移动力888pivotal stability studies关键的稳定性研究889plaque assays菌斑测定890plasmid质粒891Plasmid质粒892plasmid banks质粒库893plasminogen activators纤溶酶原激活素894Plasminogen activators纤维蛋白溶解酶原激活因子895Ploidy整倍体896pneumonia virus of mice小鼠肺炎病毒897Point mutation点突变898poisson distribution泊松分布899Polychromatic erythrocyte嗜多染红细胞900polyclonal antibody多克隆抗体901Polycyclic hydrocarbon多环芳烃902Polymer聚合物903polymerase chain reaction (PCR)聚合酶链式反应904polymorphic form多晶性型905polymorphs多晶型906polyoma virus多瘤病毒907polypeptides多肽908Polyploid cell多倍体细胞909Polyploidy多倍体910Polyploidy induction多倍体诱导911pooled havest集中回收912Poorly soluble compound难溶化合物913population doubling细胞数倍增/群体倍增914porcine猪915Positive control阳性对照916Positive result阳性结果917Post meiotic stages减数分裂后期918Post-approval批准后919Postcoital time frame交配后日期920Postimplantation deaths着床后死亡921Postnatal deaths出生后死亡922post-translational modifications批准后923post-translationally modified forms翻译后修饰924Postweaning development and growth断奶后发育和生长925potency效价926potent功效927Potential 潜在性928potential adverse consequences潜在的不良后果929potential excipients准赋形剂930Potential immunogenecity潜在免疫原性931potential impurity潜在杂质932potential new drug products准新药制剂933potential new drug substances准新药原料934Potentialtarget organs for toxicity潜在毒性靶器官935potentiometric titrimetry电位滴定936powders粉剂937power outages and human error断电和人为错误938preamble引言939Pre-and post-natal development study围产期的发育研究940Pre-and postweaning survival and growth断奶前后的存活和生长941pre-approval or pre-liscense stage批准前或发证前阶段942Precipitate沉淀物943precision精密度944preclinical and clinical studies临床前和临床研究945Preclinical safety evaluation临床前安全性评价946precursors前体947Predetermined criteria预定标准948Prediction of carcinogenicity致癌性预测949Pregnant怀孕950Pregnant and lactating animals怀孕与哺乳期动物951Preimplantation development着床前发育952Preimplantation stages of the embryo胚胎着床前期953preliminary assessment初步评估954preliminary cell bank初级细胞库955Preliminary studies预试验956Premating交配前957Premating treatment交配前给药958preparation制剂959Pre-screening预筛选960preservative防腐剂961Prevalence of abnormalities异常情况的普遍程度962Preweaning断奶前963Primary active entity主要活性实体964primary cells原代细胞965primary stability data主要稳定性数据966primary stability study/formal study/formal stability study主要稳定性研究/正式研究/正式稳定性研究967primary structure一级结构968primer引物969priming regimen接种方案970Priority selection优先选择971probability概率972process characterisation studies工艺鉴定研究973process controls工艺控制974process optimisation工艺优化975process parameters工艺参数976process validation工艺确证977process-related impurities工艺相关杂质978Pro-drug前体药物979product-related imputies产品相关杂质980progenitor祖细胞981prokaryotic cell原核细胞982Prolongation of parturition产程延长983promoters启动子984proposed commercial process模拟上市985protected samples避光样品。

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a r X i v :m a t h /0209379v 2 [m a t h .C O ] 26 N o v 2002RESTRICTED 132-DUMONT PERMUTATIONSToufik Mansour1Department of Mathematics,Chalmers University of Technology,S-41296G¨o teborg,Swedentoufik@math.chalmers.seAbstractA permutation πis said to be Dumont permutations of the first kind if each even integer in πmust be followed by a smaller integer,and each odd integer is either followed by a larger integer or is the last element of π(see,for example,[22]).In [7]Dumont showed that certain classes of permutations on n letters are counted by the Genocchi numbers.In particular,Dumont showed that the (n +1)st Genocchi number is the number of Dummont permutations of the first kind on 2n letters.In this paper we study the number of Dumont permutations of the first kind on n letters avoiding the pattern 132and avoiding (or containing exactly once)an arbitrary pattern on k letters.In several interesting cases the generating function depends only on k .Keywords:Dumont permutations,restricted permutations,generating functions.1.IntroductionClassical patterns .Let α∈S n and τ∈S k be two permutations.We say that αcontains τif there exists a subsequence 1≤i 1<i 2<···<i k ≤n such that (αi 1,...,αi k )is order-isomorphic to τ;in such a context τis usually called a pattern .We say that αavoids τ,or is τ-avoiding ,if such a subsequence does not exist.The set of all τ-avoiding permutations in S n is denoted S n (τ).For an arbitrary finite collection of patterns T ,we say that αavoids T if αavoids every τ∈T ;the corresponding subset of S n is denoted S n (T ).While the case of permutations avoiding a single pattern has attracted much attention,the case of multiple pattern avoidance remains less investigated.In particular,it is natural,as the next step,to consider permutations avoiding pairs of patterns τ1,τ2.This problem was solved completely for τ1,τ2∈S 3(see [19]),and for τ1∈S 3and τ2∈S 4(see [21]).Several recent papers [6,9,13,14,15,16]deal with the case τ1∈S 3,τ2∈S k for various pairs τ1,τ2.Another natural question is to study permutations avoiding τ1and containing τ2exactly t times.Such a problem for certain τ1,τ2∈S 3and t =1was investigated in [17],and for certain τ1∈S 3,τ2∈S k in [1,9,13,18].The tools involved in these papers include generating trees,continued fractions,Chebyshev polynomials,and Dyck words.Also,the tools involved in these papers include many classical sequences,for example sequence of Catalan numbers,Fibonacci numbers,and Pell numbers.2RESTRICTED132-DUMONT PERMUTATIONSWe denote the n th Catalan number by C n=11−4x.1−x2Q r−2(x)We denote the solution of Recurrence1.1with Q0(x)=0and Q1(x)=1by F r(x),and we denote the solution of Recurrence1.1with Q0(x)=Q1(x)=1by G r(x).For example,F2(x)=1+x2, F3(x)=1+x4,and G3(x)=1−x2+x41−x2r−2m=r−1−j(1−x2F m(x))and G r(x)=1+r−1 j=1x2jRESTRICTED132-DUMONT PERMUTATIONS3 ing Recurrence1.1it is easy to see that√x)=1+x+F4((3·2n−2−1)x n,n≥2where f n is the n th Fibonacci number.Organization of the paper.In this paper we use generating function techniques to study those Dumont permutations in S n(n≥0)which avoid132and avoid(or contain exactly once)an arbitrary pattern on k letters.In several interesting cases the generating function depends only on k.The paper is organized as follows.The case of Dumont permutations avoiding both132andτis treated in Section2.We present a simple structure for any Dumont permutation avoiding132.This structure can be obtained explicitly for several interesting cases,including classical patterns and generalized patterns.This allows us tofind explicitly some statistics on Dumont permutations which avoid132. The case of avoiding132and containing another patternτexactly once is treated in Section3.Again, wefind explicitly the generating function for several interesting cases ofτ,including classical patterns and generalized patterns.Most of the explicit solutions obtained in Sections2-4involve the generating functions F k(x)and G k(x).2.Dumont permutations which avoid132and another patternLet D is the set of all Dumont permutations of all sizes including the empty permutation.Let Dτ(n) denote the number of Dumont permutations in S n(132,τ),and let Dτ(x)= n≥0Dτ(n)x n be the corresponding generating function.In this section we describe a method for enumerating Dumont permutations which avoid132and another pattern and we use our method to enumerate Dτ(n)for variousτ.We begin with an observation concerning the structure of the Dumnot permutations of the first kind avoiding132which holds immediately from definitions.Proposition2.1.For anyπ∈D n(132)such thatπj=n,there holds one of the following assertions:(1)if n is odd number thenπ=(π′,n),whereπ′∈D n−1(132);(2)if n is even number thenπ=(π′,n,π′′)such thatπ′is a Dumont permutation on the numbersn−j+1,n−j+2,...,n−1,π′′is nonempty Dumont permutation on the numbers1,2,···,n−j, and j=1,2,4,...,n−2(the minimal element ofπ′cannot be even number).2.1.τ=∅.As a corollary of Proposition2.1wefind an explicit formula for the number of132-avoiding Dumont permutations in S n.Theorem2.2.The generating function for the number of132-avoiding Dumont permutations in S n is given by(1+x)C(x2).In other words,the number of132-avoiding Dumont permutations in S n is given by C[n/2],which is the[n/2]th Catalan number.Proof.By Proposition2.1,we have two possibilities for block decomposition of an arbitraryπ∈D n(132).Let us write an equation for D∅(x).The contribution of thefirst decomposition above equalsD∅(2n+1)x2n+1=x n≥0D∅(2n)x2n,n≥04RESTRICTED 132-DUMONT PERMUTATIONSequivalently,(2.1)D ∅(x )−D ∅(−x )=x (D ∅(x )+D ∅(−x )).The contribution of the second decomposition above equalsn ≥1D ∅(2n )x2n=n ≥1D ∅(2n −1)x2n+n ≥1n j =0D ∅(2j +1)D ∅(2n +2−2j )x 2n ,equivalently,(2.2)D ∅(x )+D ∅(−x )−2==x (D ∅(x )−D ∅(−x ))+x2(D 12...k (x )+D 12...k (−x ))and B k (x )=12(D 12...(k −1)(x )−D 12...(k −1)(−x ))(D 12...k (x )+D 12...k (−x )−2).The rest is easy to check by the definitions of A k and B k .Example 2.5.Theorem2.4,for k =3,yields D 123(x )=1+x +x 4−x 5(1+x )(1−x 2−x 4).Inother words,the number of 132-avoiding Dumont permutation in S n (1234)is f n/2+2+f n/2−2if n is even number,otherwise 2for all n ≥2,where f n is the n th Fibonacci number.As an extension of Theorem 2.4,let us defineA (x 1,x 2,x 3,...)=π∈Dj ≥1x 12...j (π)j,where τ(π)is the number of occurrences of τin π.LetA (1)(x 1,x 2,x 3,...)=12(A (x 1,x 2,x 3,...)−A (−x 1,x 2,x 3,...)).Using the same arguments as in the proof of Theorem 2.4,we obtain the following.RESTRICTED 132-DUMONT PERMUTATIONS 5Theorem 2.6.We haveA(1)(x 1,x 2,x 3,...)=1+x 21A(1)(x 1x 2,x 2x 3,x 3x 4, (1)x2...=C (x 2).Hence,we have D ∅(x )=(1+x )C (x 2)(see Theorem2.2).Another application of Theorem 2.6is to the number of right to left maxima.Let π∈S n ,πi is aright to left maxima if πi >πj for all i <j .We denote the number of right to left maxima of πby rlm (π).Proposition 5of [3]provedlrm (π)=j ≥112...j (π)(−1)j −1.Therefore,π∈Dx |π|y rlm (π)=A (xy,y −1,y,y −1,...)together with Theorem 2.6and A (1)(x,1,1,...)=C (x 2)we getπ∈Dx |π|y rlm (π)=1+xC (x 2)y +n ≥2x 2n −2C n −1(x 2)y n .Corollary 2.7.The generating function for the number of Dumont permutations avoiding 132andhaving exactly k right to left maxima is given by x 2k −2C k −1(x 2)for all k ≥2,and x k C k (x 2)for k =0,1.2.3.A classical pattern τ=2134...k .Similarly as in Theorem 2.4,we obtain the case τ=2134...k .Theorem 2.8.For all k ≥2,D 213...k (x )=G k −1(x )+xG k −2.Example 2.9.Theorem 2.8for k =3,4yields D 213(x )=1+x −x 3(1−x 2)2.6RESTRICTED132-DUMONT PERMUTATIONS2.4.A generalized pattern12-3-···-k.In this subsection we use the notation of generalized pat-terns(see Section1).For example,we write the classical pattern132as1-3-2.By definitions,we get D12(x)=1+x+x2.So,by the same arguments as in the proof of Theorem2.4, together withD12(x)=D1-2(x)=1+x+x2,we obtain the following.Theorem2.10.For all k≥1,D12-3-...-k(x)=D1-2-3-...-k(x)=F k(x)+xF k−1(x).A comparison of Theorem2.4with Theorem2.10suggests that there should exist a bijection between the sets S n(1-3-2,12-3-···-k)and S n(1-3-2,1-2-3-···-k).However,we failed to produce such a bijection,andfinding it remains a challenging open question.Now,let us defineB(x1,x2,x3,...)= π∈D x1(π)1 j≥2x12-3-...-j(π),1whereτ(π)is the number of occurrences ofτinπ.LetA(2)(x1,x2,x3,...)=1(B(x1,x2,x3,...)−B(−x1,x2,x3,...)).2Using the same arguments as those in the proof of Theorem2.4,we getTheorem2.11.x21(1−x2+x2A(2)(x1,x2x3,x3x4,...))A(2)(x1,x2,x3,...)=1+1−4x2yRESTRICTED132-DUMONT PERMUTATIONS7 2.5.A generalized patternτ=21-3-···-k.In this subsection,we use the notation of generalized patterns(see Section1).For example,we write the classical pattern132as1-3-2.By definitions,we get D21(x)=1+x.So,by the same arguments as in the proof of Theorem2.4 together withD21(x)=D2-1(x)=1+x,we obtain the following.Theorem2.13.For all k≥2,D21-3-...-k(x)=D2-1-3-...-k(x)=G k−1(x)+xG k−2(x).A comparison of Theorem2.8with Theorem2.13suggests that there should exist a bijection between the sets S n(1-3-2,21-3-···-k)and S n(1-3-2,2-1-3-···-k).However,we failed to produce such a bijection,andfinding it remains a challenging open question.Now,let us defineC(x1,x2,x3,...)= π∈D x1(π)1 j≥2x21-3-...-j(π),1whereτ(π)is the number of occurrences ofτinπ.LetA(3)(x1,x2,x3,...)=1(C(x1,x2,x3,...)−C(−x1,x2,x3,...)).2Using the same arguments as in the proof of Theorem2.4,we get the following.Theorem2.14.We havex21x2A(3)(x1,x2x3,x3x4,...)A(3)(x1,x2,x3,...)=1+1−x2−x2F k−3(x).8RESTRICTED132-DUMONT PERMUTATIONSing the same arguments as in the proof of Theorem2.2we getD23...k1(x)−D23...k1(−x)=x(D23...k1(x)+D23...k1(−x)),andD23...k1(x)+D23...k1(−x)−2=x(D23...k1(x)−D23...k1(−x))++x1−2x2−x4.In other words,the number of Dumont permutation in S n(132,23451)is given by P[n/2],which is the[n/2]th Pell number for all n≥2.3.Dumont permutations which avoid132and contain another pattern exactly once Let Dτ;r(n)denote the number of Dumont permutations in S n(132)containingτexactly r times, and let Dτ;r(x)= n≥0Dτ;r(n)x n be the corresponding generating function.3.1.A classical patternτ=12...k.Theorem3.1.LetA k(x)=x2(1−x2F k−2(x))2A k−2(x)for all k≥2,where A1(x)=0and A2(x)=x4.Then for all k≥2D12...k;1(x)=A k(x)+xA k−1(x).Proof.By Proposition2.1,we have two possibilities for the block decomposition of an arbitraryπin D n(132).Let us write an equation for D12...k;1(x).The contribution of thefirst decomposition above isn≥0D12...k;1(2n+1)x2n+1=x n≥0D12...(k−1);1(2n)x2n,equivalently(3.1)D12...k;1(x)−D12...k;1(−x)=x(D12...(k−1);1(x)+D12...(k−1);1(−x)).The contribution of the second decomposition above isn≥1D12...k;1(2n)x2n= n≥1D12...k;1(2n−1)x2n++ n≥1n j=0D12...(k−1);1(2j+1)D12...k;0(2n+2−2j)x2n++ n≥1n j=0D12...(k−1);0(2j+1)D12...k;1(2n+2−2j)x2n, equivalently(3.2)D12...k;1(x)+D12...k;1(−x)=x(D12...k;1(x)−D12...k;1(−x))++x2(D12...(k−1);0(x)−D12...(k−1);0(−x))(D12...k;1(x)+D12...k;1(−x)).Using Theorem2.4,Equation3.1,Equation3.2,and Definition1.1,we get the desired result.RESTRICTED132-DUMONT PERMUTATIONS9 Example3.2.Theorem3.1for k=3we getD123;1(x)=x5(1+x−x2)(1−x2)(1−x2−x4)2.As an extension of Theorem3.1,let us consider the case r≥1.Theorem2.6,for given k and r,yields an explicit formula for D12...k;r(x).For example,for k=3and r=0,1,2,3,4,we have the following. Theorem3.3.We have(i)D123;0(x)=1+x+x4−x51−x2;(iii)D123;2(x)=x5(1+x2)(1+2x−2x2−x3+x4)(1−x2)2;(v)D123;4(x)=x9(1+x2)(−1−3x+3x2+3x3−3x4−x5+x6)1−x2G k−2(x)A k−1(x)+x4G k−1(x)1−x2.Then,for all k≥2,D213...k;1(x)=A k(x)+xA k−1(x).3.3.A generalized patternsτ=12-3-···-k andτ=21-3-···-k.Similarly to Theorem3.1,we getTheorem3.5.LetA k(x)=x2(1−x2F k−2(x))2A k−2(x)for all k≥4,where A1(x)=x2and A2(x)=2x4.Then,for all k≥2,D12-3-···-k;1(x)=A k(x)+xA k−1(x).As an extension of Theorem3.5,let us consider the case r≥1.Theorem2.11,for given k and r, yields an explicit formula for D12-3-···-k;r(x).For example,for k=3and r=0,1,2,3,4,we have the following.10RESTRICTED132-DUMONT PERMUTATIONSTheorem3.6.We have(i)D12-3;0(x)=1+x+x4−x5(1−x2)2;(iii)D12-3;2(x)=x7(2+2x−6x2−x3+6x4+x5−2x6)(1−x2)4;(v)D12-3;4(x)=x9(5+5x−23x2−7x3+40x4−x5−30x6+5x7+5x8−x9+5x10+x11−2x12)1−x2G k−2(x)A k−1(x)+x4G k−1(x)1−x2,and A4(x)=x6(2−x2)1−x2;(ii)D21-3;1(x)=x3(1+x−x2)(1−x2)2;(iv)D21-3;3(x)=x5(1+x−x2+x3−x4−x5+x6)(1−x2)3.4.Further resultsHere we present three different directions to generalize the results of the previous sections.Thefirst of these directions is to consider one occurrence of the classical pattern132.For example,the following result is true.RESTRICTED132-DUMONT PERMUTATIONS11 Theorem4.1.There does not exist a Dumont permutation containing132(classical pattern)exactly once.Proof.Letπ=(π′,n,π′′)be a Dumont permutation of length n,which contains the pattern132 exactly once.It is easy to see that there does not exist a Dumont permutation where n=0,1,2,3. Suppose n≥4,and let us assume by induction on n that there does not exist a Dumont permutation of length m≤n−1containing132exactly once.To prove this property for n,let us consider the following two cases together using Proposition2.1:n is either an even number,or n is an odd number.(1)Let n be an odd number.Sinceπis a Dumont permutation,we getπ′′=∅,soπcontains132exactly once if and only ifπ′contains132exactly once.(2)Let n be an even number.Sinceπis a Dumont permutation we haveπ′′=∅.Now,let usconsider two cases:either n does not appear in the occurrence of132,or n does.(a)Let the occurrence of132not contain the element n.So,every element ofπ′is greater thanevery element ofπ′′.Therefore,eitherπ′is a Dumont permutation of length m≤n−2that contains132exactly once,orπ′′is a Dumont permutation of length m≤n−1thatcontains132exactly once.(b)Let the occurrence of132contain the element n.So,π=(π′,a,n,π′′,a+1,π′′′)(see[16])such thatπp=n andπq=a+1,where every element ofπ′is greater than every elementofπ′′and every element ofπ′′is greater than every element ofπ′′′.Since n is evennumber and maximal inπwe have that a is an odd number,so a+1is an even number.Therefore,by using Proposition2.1we get that p,q are even numbers,(π′,a)is of oddlength,andπ′′is of even length.On the other hand,q=p+1+|π′′|,so q is an oddnumber,a contradiction.Hence,by induction on n we get the desired result.The second direction is to consider more than one additional restriction.For example,the following result is true.Theorem 4.2.Let k≥2.The generating function for the number of Dumont permutations in S n(1-3-2,1-2-3···-k,2-1-3···-k)is given byG k−1(x)+xG k−2(x).A comparison of Theorem4.2with Theorem2.8suggests that there should exist a bijection between the sets S n(1-3-2,2-1-3-···-k)and S n(1-3-2,1-2-3···-k,2-1-3-···-k).However,we failed to produce such a bijection,andfinding it remains an open question.The third direction is to consider another3-letter pattern instead of1-3-2.Theorem4.3.The number of Dumont permutation of the second kind in S n(3-2-1)is the same as the number of Dumont permutation in S n(2-3-1)(or in S n(3-1-2))which is equal to C[n/2].Acknowledgments:The author is grateful to S.Kitaev and the anonymous refree for their careful reading of the manuscript.12RESTRICTED132-DUMONT PERMUTATIONSReferences[1]M.Atkinson,Restricted permutations,Discr.Math.195(1999),27–38.[2]E.Babson and E.Steingr´ımsson,Generalized permutation patterns and a classification of the Mahonianstatistics,S´e minaire Lotharingien de Combinatoire,B44b:18pp,(2000).[3]P.Br¨a nd´e n,A.Claesson,and E.Steingr´ımsson,Continued fractions and increasing subsequences in permuta-tions,Discr.Math.,to appear.[4]A.Claesson,Generalised pattern avoidance,European Journal of Combinatorics,22(2001)961–973.[5]A.Claesson and T.Mansour,Permutations avoiding a pair of generalized patterns of length three with exactlyone dash,preprint CO/0107044.[6]T.Chow and J.West,Forbidden subsequences and Chebyshev polynomials,Discr.Math.204(1999)119–128.[7]D.Dumont,Interpretations combinatoires des nombres de Genocchi,Duke Math.J.41(1974),305–318.[8]S.Kitaev,Multi-avoidance of generalised patterns,to appear in Discrete Mathematics.[9]C.Krattenthaler,Permutations with restricted patterns and Dyck paths,Adv.in Applied Math.27(2001),510–530.[10]T.Mansour,Continued fractions and generalized patterns,European Journal of Combinatorics,23:3(2002),329–344.[11]T.Mansour,Restricted1-3-2permutations and generalized patterns,Annals of Combinatorics6(2002),1–12.[12]T.Mansour,Continued fractions,statistics,and generalized patterns,Ars Combinatoria,to appear(2002),preprint CO/0110040.[13]T.Mansour and A.Vainshtein,Restricted permutations,continued fractions,and Chebyshev polynomialsElectronic bin.7(2000)#R17.[14]T.Mansour and A.Vainshtein,Restricted132-avoiding permutations,Adv.Appl.Math.126(2001),258–269.[15]T.Mansour and A.Vainshtein,Layered restrictions and Chebychev polynomials(2000),Annals of Combina-torics5(2001),451–458.[16]T.Mansour and A.Vainshtein,Restricted permutations and Chebyshev polynomials,S´e minaire Lotharingiende Combinatoire47(2002),Article B47c.[17]A.Robertson,Permutations containing and avoiding123and132patterns,Discrete Mathematics and Theo-retical Computer Science,3(1999)151–154.[18]A.Robertson,H.Wilf,and D.Zeilberger,Permutation patterns and continued fractions,Electronic bin.6(1999)#R38.[19]R.Simion,F.W.Schmidt,Restricted Permutations,Europ.J.of Combinatorics6(1985),383–406.[20]N.J.A.Sloane and S.Plouffe,The Encyclopedia of Integer Sequences,Academic Press,New York(1995).[21]J.West,Generating trees and forbidden subsequences,Discr.Math.157(1996),363–372.[22]————,Available in http://www.theory.csc.uvic.ca/∼cos/inf/perm/GenpcchhiInfo.html.。

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