A practical reference on 强制降解: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.
This page was last updated on 2026-03-08 and is reviewed periodically as new material appears.
Receptor activation raises intracellular cyclic AMP through Gs coupling, which promotes glucose-dependent insulin release and suppresses glucagon secretion when blood glucose is elevated. Effects outside the pancreas include slower gastric emptying and altered appetite signalling in the hypothalamus and hindbrain. The relative contribution of each tissue to overall metabolic outcomes remains an area of active investigation. Central mechanisms in particular are inferred mainly from animal models and indirect human measures rather than direct observation.
Serum protein binding dominates the pharmacokinetic profile. The attached chain associates strongly with albumin, shielding the peptide from enzymatic attack and slowing filtration by the kidney. This interaction extends the circulation half-life to roughly one week in humans, which supports weekly administration intervals. An oral version pairs the peptide with an absorption enhancer that transiently alters gastric epithelium, permitting limited uptake; bioavailability by that route is substantially lower than by injection.
市售注射用制剂通常要求在二至八摄氏度冷藏保存,并避免光照与冻结。部分多剂量笔在首次使用后允许在不超过三十摄氏度的环境中存放有限周数,具体期限由辅料与防腐剂体系决定。反复冻融会促进肽链聚集并改变可见颗粒计数,因此应予避免。冻干粉末在干燥、避光、低温条件下更为稳定。溶液配制后宜使用低吸附容器,以减少肽类在塑料或玻璃表面的损失。
纯度评价多采用反相高效液相色谱,流动相常加入三氟乙酸或甲酸作为离子对改性剂,检测波长设在二百一十四纳米或二百二十纳米。分子量确认依靠电喷雾电离质谱或基质辅助激光解吸电离质谱,实测值应与理论值在数 ppm 内吻合。肽图分析通过酶切后液相色谱串联质谱完成,用于核查序列与修饰位点。体积排阻色谱用于定量共价与非共价聚集体。生物基质浓度测定则采用免疫分析或液相色谱串联质谱。
肽类的主要降解路径包括天冬酰胺脱酰胺、甲硫氨酸氧化、天冬氨酸异构化以及由 β-折叠驱动的聚集,这些反应对 pH 与缓冲液种类较为敏感。磷酸盐、丙二醇与苯酚等辅料会影响局部微环境与界面行为。强制降解研究借助高温、强光、氧化剂与极端 pH 暴露来预测产物谱。关于长期室温存放的数据相对有限,超出标签条件的稳定性仍属开放问题,需要在具体制剂中通过实时与加速试验加以确认。
| Property | Value | Notes |
|---|---|---|
| Molecular class | Synthetic peptide, GLP-1 receptor agonist | 31 amino acid residues |
| Molecular formula | C187H291N45O59 | free peptide, no counter-ion |
| Approximate mass | 4114 Da | matches theoretical value |
| Receptor target | Glucagon-like peptide-1 receptor | Gs-coupled, cyclic AMP pathway |
| Circulation half-life | About one week in humans | extended by albumin association |
Semaglutide dissolves readily in water and in aqueous buffers near neutral pH. Solubility decreases near the isoelectric point, where net charge is minimal. Common laboratory solvents include phosphate-buffered saline and dilute ammonium bicarbonate. Strongly acidic or basic conditions may accelerate hydrolysis. Working concentrations are usually prepared by diluting a concentrated stock. Vial surfaces can adsorb small amounts of peptide at low concentrations, so carrier proteins or low-binding tubes are sometimes used.
Reverse-phase high-performance liquid chromatography is the standard method for purity assessment, separating the peptide from truncated or oxidized variants. Mass spectrometry confirms molecular mass and detects modifications, while ultraviolet absorbance near 280 nanometers supports concentration measurement through tryptophan and tyrosine residues. Circular dichroism can indicate secondary structure, though the peptide is largely helical in solution, and ion-exchange chromatography resolves charge variants. Purity values above 95 percent are typical for research-grade material. Stability studies track degradation over time under defined conditions.
Development began in the early 2010s with the goal of extending GLP-1 activity beyond the brief window achieved by native peptide infusion. The earliest approved formulation was a subcutaneous injection given once weekly. A later oral tablet pairs the peptide with an absorption enhancer, sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, usually shortened to SNAC. That carrier lowers local pH and helps the peptide cross gastric tissue. Both routes deliver the same active molecule.
Semaglutide is a synthetic peptide analog of human glucagon-like peptide-1, a gut hormone released after meals. Its backbone retains the GLP-1 sequence but incorporates two substitutions that slow enzymatic breakdown by dipeptidyl peptidase-4. A short polyethylene glycol linker and a C18 fatty diacid are attached to the peptide chain, allowing the molecule to bind serum albumin and remain in circulation far longer than the native hormone. The result is a circulating half-life measured in days rather than the minutes typical of endogenous GLP-1.
Receptor activation occurs at GLP-1 receptors distributed across pancreatic islets, the hypothalamus, and the gastrointestinal tract. Binding triggers G protein signaling that raises cyclic AMP and enhances glucose-dependent insulin release. Because the effect depends on prevailing glucose levels, insulin secretion does not rise when blood sugar is already low. Signaling in the brain and gut also influences appetite and gastric emptying, which is why the compound appears in both metabolic and weight-related research literature.
Two principal therapeutic variants exist under separate regulatory filings, one indicated for glycemic control in type 2 diabetes and one for chronic weight management. Both use the same active molecule; differences lie in formulation strength, titration schedule, and labeling. Regulatory agencies in the United States and European Union approved injectable forms in 2017 and 2018 respectively. An oral tablet formulation received approval later, using a carrier molecule to enhance absorption across the gastric epithelium. Labeling differs by jurisdiction and by indication.
The distinction between established facts and open questions matters here. That the peptide binds the GLP-1 receptor and stimulates insulin release in a glucose-dependent manner is well documented. How individual variability in receptor density, gastric emptying rate, and gut microbiome composition shapes response remains an active research area. Long-term outcomes beyond five years of continuous use are not yet fully characterized in published trials, and several extension studies are ongoing.
Reversed-phase high-performance liquid chromatography with ultraviolet detection is the dominant approach for peptide purity assessment, usually paired with mass spectrometry to confirm molecular mass and sequence. Peptide mapping by enzymatic digestion and tandem mass spectrometry locates modifications such as deamidation and oxidation. Quantitation in plasma matrices can be performed by LC-MS/MS after solid-phase extraction. Method validation follows general guidance on accuracy, precision, linearity, and limits of detection. Comparability of results between laboratories, when no shared reference standard is available, remains an open question.
Stability studies focus on deamidation of asparagine and glutamine residues, oxidation of methionine, and aggregation into higher-order species. The fatty acid side chain adds susceptibility to oxidative change and can promote self-association at high concentration. Lyophilised material is comparatively robust when kept cold and dry, while aqueous solutions require refrigeration and protection from light. Forced degradation experiments under heat, acid, base, and peroxide conditions establish the specificity of each analytical method. Which degradation route dominates under real storage conditions depends on the formulation and stays formulation-specific.
=== Confusion with the Fanning friction factor === The Darcy–Weisbach friction factor fD is 4 times larger than the Fanning friction factor f, so attention must be paid to note which one of these is meant in any "friction factor" chart or equation being used. Of the two, the Darcy–Weisbach factor fD is more commonly used by civil and mechanical engineers, and the Fanning factor f by chemical engineers, but care should be taken to identify the correct factor regardless of the source of the chart or formula. Note that
== ISO 9000 – ISO 9999 == ISO 9000:2015 Quality management systems – Fundamentals and vocabulary ISO 9001:2015 Quality management systems – Requirements ISO/TS 9002:2016 Quality management systems – Guidelines for the application of ISO 9001:2015 ISO 9004:2018 Managing for the sustained success of an organization – A quality management approach ISO/TR 9007:1987 Information processing systems - Concepts and terminology for the conceptual schema and the information base ISO 9019:1995 Securities – Numbering of certificates ISO 9022 Optics and optical instruments - Environmental test methods ISO 9022-1:2016 Definitions, extent of testing ISO 9022-2:2015 Cold, heat and humidity ISO 9022-3:2015 Mechanical stress ISO 9022-4:2014 Salt mist ISO 9022-5:1994 Combined cold, low air pressure [Withdrawn: replaced by ISO 9022-23:2016] ISO 9022-6:2015 Dust ISO 9022-23:2016 Low pressure combined with cold, ambient temperature and dry or damp heat ISO 9031:1987 Air cargo equipment - Handling systems for unit load devices (ULDs) - Symbols for pictorial representation ISO 9036:1987 Information processing - Arabic 7-bit coded character set for information interchange ISO/IEC 9040:1997 Information technology – Open Systems Interconnection – Virtual Terminal Basic Class Service ISO/IEC 9041 Information technology – Open Systems Interconnection – Virtual Terminal Basic Class Protocol ISO/IEC 9041-1:1997 Part 1: Specification ISO/IEC 9041-2:1997 Part 2: Protocol Implementation Conformance Statement (PICS) proforma ISO 9045:1990 Industrial screens and screening – Vocabulary ISO 9050 Glass in building – Determination of light transmittance, solar direct transmittance, total solar energy transmittance, ultraviolet transmittance and related glazing factors ISO 9060: Solar energy -- Specification and classification of instruments for measuring hemispherical solar and direct solar radiation ISO/IEC 9066 Information technology – Open Systems Interconnection – Reliable Transfer ISO/IEC 9066-1:1989 Part 1: Model and service definition ISO/IEC 9066-2:1989 Part 2: Protocol specification ISO/IEC 9066-3:1996 Protocol Implementation Conformance Statement (PICS) proforma ISO 9069:1988 Information processing – SGML support facilities – SGML Document Interchange Format (SDIF) ISO/IEC 9070:1991 Information technology - SGML support facilities - Registration procedures for public text owner identifiers ISO/IEC 9072 Information technology – Open Systems Interconnection – Remote Operations ISO/IEC 9072-1:1989 Part 1: Model, notation and service definition ISO/IEC 9072-2:1989 Part 2: Protocol specification ISO/IEC 9072-3:1996 Protocol Implementation Conformance Statement (PICS) proforma ISO/IEC 9075 Information technology – Database languages – SQL ISO 9086 Wood – Methods of physical and mechanical testing – Vocabulary ISO 9086-1:1987 Part 1: General concepts and macrostructure ISO 9092:2011 Textiles – Nonwovens – Definition ISO 9095:1990 Steel tubes – Continuous character marking and colour coding for material identification ISO 9123:2001 Measurement of liquid flow in open channels – Stage-fall-discharge relationships ISO/IEC 9126 Software engineering – Product quality ISO 9128:2006 Road vehicles - Graphical symbols to designate brake fluid types ISO 9141 Road vehicles – Diagnostic systems ISO 9141-2 CARB requirements for interchange of digital information ISO 9141-3 Verification of the communication between vehicle and OBD II scan tool ISO 9144:1991 Securities – Optical character recognition line – Position and structure ISO 9160:1988 Information processing - Data encipherment - Physical layer interoperability requirements ISO 9170 Terminal units for medical gas pipeline systems ISO 9170-1:2017 Part 1: Terminal units for use with compressed medical gases and vacuum ISO 9170-2:2008 Part 2: Terminal units for anaesthetic gas scavenging systems ISO/IEC 9171 Information technology - 130 mm optical disk cartridge, write once, for information interchange ISO/IEC 9171-1:1990 Part 1: Unrecorded optical disk cartridge ISO/IEC 9171-2:1990 Part 2: Recording format ISO 9175 Tubular tips for hand-held technical pens using India ink on tracing paper ISO 9175-1:1988 Part 1: Definitions, dimensions, designation and marking ISO 9177 Mechanical pencils for technical drawings ISO 9177-1:2016 Part 1: Classification, dimensions, performance requirements and testing ISO 9177-2:1989 Part 2: Black leads – Classification and dimensions ISO 9177-3:1994 Part 3: Black leads – Bending strengths of HB leads ISO 9180:1988 Black leads for wood-cased pencils – Classification and diameters ISO 9186 Graphical symbols - Test methods ISO 9186-1:2014 Part 1: Method for testing comprehensibility ISO 9186-2:2008 Part 2: Method for testing perceptual quality ISO 9186-3:2014 Part 3: Method for testing symbol referent association ISO 9187 Injection equipment for medical use ISO 9187-1:2010 Part 1: Ampoules for injectables ISO 9187-2:2010 Part 2: One-point-cut (OPC) ampoules ISO 9195:1992 Liquid flow measurement in open channels – Sampling and analysis of gravel-bed material ISO 9196:1992 Liquid flow measurement in open channels – Flow measurements under ice conditions ISO 9211 Optics and photonics - Optical coatings ISO 9211-1:2010 Part 1: Definitions ISO/TR 9212:2015 Hydrometry – Methods of measurement of bedload discharge ISO 9222 Technical drawings – Seals for dynamic application ISO 9222-1:1989 Part 1: General simplified representation ISO 9222-2:1989 Part 2: Detailed simplified representation ISO 9223 Corrosion of metals and alloys - Corrosivity of atmospheres - Classification, determination and estimation ISO 9224 Corrosion of metals and alloys - Corrosivity of atmospheres - Guiding values for the corrosivity categories ISO 9225 Corrosion of metals and alloys - Corrosivity of atmospheres - Measurement of environmental parameters affecting corrosivity of atmospheres ISO 9226 Corrosion of metals and alloys - Corrosivity of atmospheres - Determination of corrosion rate of standard specimens for the evaluation of corrosivity ISO 9227:2017 Corrosion tests in artificial atmospheres – Salt spray tests ISO 9229:2007 Thermal insulation - Vocabulary ISO 9230:2007 Information and documentation - Determination of price indexes for print and electronic media purchased by libraries ISO 9232:2003 Yogurt – Identification of characteristic microorganisms (Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus) ISO 9235:2013 Aromatic natural raw materials – Vocabulary ISO 9241 Ergonomics of human-system interaction ISO 9244:2008 Earth-moving machinery - Machine safety labels - General principles ISO 9245:1991 Earth-moving machinery – Machine productivity – Vocabulary, symbols and units ISO 9247:1990 Earth-moving machinery – Electrical wires and cables – Principles of identification and marking ISO/TS 9250 Earth-moving machinery – Multilingual listing of equivalent terms ISO/TS 9250-1:2012 Part 1: General ISO/TS 9250-2:2012 Part 2: Performance and dimensions ISO 9251:1987 Thermal insulation - Heat transfer conditions and properties of materials - Vocabulary ISO 9264:1988 Woodworking machines – Narrow belt sanding machines with sliding table or frame – Nomenclature ISO 9265:1988 Woodworking machines – Multi-spindle boring machines – Nomenclature ISO 9266:1988 Woodworking machines – Universal tool and cutter sharpeners – Nomenclature ISO 9267:1988 Woodworking machines – Bandsaw blade sharpening machines – Nomenclature ISO 9268:1988 Implants for surgery – Metal bone screws with conical under-surface of head – Dimensions ISO 9269:1988 Implants for surgery – Metal bone plates – Holes and slots corresponding to screws with conical under-surface ISO/IEC 9281 Information technology - Picture coding methods ISO/IEC 9281-1:1990 Part 1: Identification ISO/IEC 9281-2:1990 Part 2: Procedure for registration ISO/IEC 9282 Information processing - Coded representation of pictures ISO/IEC 9282-1:1988 Part 1: Encoding principles for picture representation in a 7-bit or 8-bit environment ISO 9288:1989 Thermal insulation – Heat transfer by radiation – Physical quantities and definitions ISO/IEC 9293:1994 Information technology – Volume and file structure of disk cartridges for information interchange ISO 9295:2015 Acoustics - Determination of high-frequency sound power levels emitted by machinery and equipment ISO 9296:2017 Acoustics - Declared noise emission values of information technology and telecommunications equipment ISO 9300:2005 Measurement of gas flow by means of critical flow Venturi nozzles ISO 9308 Water quality – Enumeration of Escherichia coli and coliform bacteria ISO 9308-1:2014 Part 1: Membrane filtration method for waters with low bacterial background flora ISO 9308-2:2012 Part 2: Most probable number method ISO 9308-3:1998 Part 3: Miniaturized method (Most Probable Number) for the detection and enumeration of E. coli in surface and waste water ISO 9314 Information processing systems Fibre Distributed Data Interface (FDDI) ISO 9314-1:1989 Part 1: Token Ring Physical Layer Protocol (PHY) ISO 9314-2:1989 Part 2: Token Ring Media Access Control (MAC) ISO/IEC 9314-3:1990 Part 3: Physical Layer Medium Dependent (PMD) ISO/IEC 9314-4:1999 Part 4: Single Mode Fibre Physical Layer Medium Dependent (SMF-PMD) ISO/IEC 9314-5:1995 Part 5: Hybrid Ring Control (HRC) ISO/IEC 9314-6:1998 Part 6: Station Management (SMT) ISO/IEC 9314-7:1998 Part 7: Physical layer Protocol (PHY-2) ISO/IEC 9314-8:1998 Part 8: Media Access Control-2 (MAC-2) ISO/IEC 9314-9:2000 Part 9: Low-cost fibre physical layer medium dependent (LCF-PMD) ISO/IEC 9314-13:1998 Part 13: Conformance Test Protocol Implementation Conformance Statement (CT-PICS) Proforma ISO/IEC 9314-20:2001 Part 20: Abstract test suite for FDDI physical medium dependent conformance testing (FDDI PMD ATS) ISO/IEC 9314-21:2000 Part 21: Abstract test suite for FDDI physical layer protocol conformance testing (FDDI PHY ATS) ISO/IEC 9314-25:1998 Part 25: Abstract test suite for FDDI - Station Management Conformance Testing (SMT-ATS) ISO/IEC 9314-26:2001 Part 26: Media Access Control Conformance Testing (MAC-ATS) ISO 9315:1989 Information processing systems - Interface between flexible disk cartridge drives and their host controllers ISO/IEC 9316:1995 Information technology - Small Computer System Interface-2 ISO/IEC 9316-2:2000 Information technology - Small computer system interface-2 (SCSI-2) - Part 2: Common Access Method (CAM) Transport and SCSI interface module ISO/IEC 9318 Information technology - Intelligent Peripheral Interface ISO/IEC 9318-2:1990 Part 2: Device specific command set for magnetic disk drives ISO/IEC 9318-3:1990 Part 3: Device generic command set for magnetic and optical disk drives ISO/IEC 9318-4:2002 Part 4: Device generic command set for magnetic tape drives (IPI-3 tape) ISO 9334:2012 Optics and photonics - Optical transfer function - Definitions and mathematical relationships ISO 9335:2012 Optics and photonics - Optical transfer function - Principles and procedures of measurement ISO 9342 Optics and optical instruments – Test lenses for calibration of focimeters ISO 9342-1:2005 Part 1: Test lenses for focimeters used for measuring spectacle lenses ISO 9342-2:2005 Part 2: Test lenses for focimeters used for measuring contact lenses ISO 9346:2007 Hygrothermal performance of buildings and building materials – Physical quantities for mass transfer – Vocabulary ISO 9360 Anaesthetic and respiratory equipment – Heat and moisture exchangers (HMEs) for humidifying respired gases in humans ISO 9360-1:2000 Part 1: HMEs for use with minimum tidal volumes of 250 ml ISO 9360-2:2001 Part 2: HMEs for use with tracheostomized patients having minimum tidal volumes of 250 ml ISO 9362:2014 Banking – Banking telecommunication messages – Business identifier code (BIC) ISO 9368 Measurement of liquid flow in closed conduits by the weighing method – Procedures for checking installations ISO 9368-1:1990 Part 1: Static weighing systems ISO 9394:2012 Ophthalmic optics – Contact lenses and contact lens care products – Determination of biocompatibility by ocular study with rabbit eyes ISO 9407 Shoe sizes – Mondopoint system of sizing and marking ISO 9431:1990 Construction drawings – Spaces for drawing and for text, and title blocks on drawing sheets ISO/TR 9464:2008 Guidelines for the use of ISO 5167:2003 ISO 9488:1999 Solar energy - Vocabulary ISO 9493:2010 Geometrical product specifications (GPS) – Dimensional measuring equipment: Dial test indicators (lever type) – Design and metrological characteristics ISO/IEC 9496:2003 CHILL - The ITU-T programming language ISO 9506 Industrial automation systems - Manufacturing Message Specification ISO/IEC 9529 Information processing systems - Data interchange on 90 mm (3,5 in) flexible disk cartridges using modified frequency modulation recording at 15 916 ftprad, on 80 tracks on each side ISO/IEC 9541 Information technology – Font information interchange ISO/IEC 9541-1:2012 Part 1: Architecture ISO/IEC 9541-2:2012 Part 2: Interchange Format ISO/IEC 9541-3:2012 Part 3: Glyph shape representation ISO/IEC 9541-4:2009 Part 4: Harmonization to Open Font Format ISO 9542:1988 Information processing systems – Telecommunications and information exchange between systems – End system to Intermediate system routeing exchange protocol for use in conjunction with the Protocol for providing the connectionless-mode network service (ISO 8473) ISO 9543:1989 Information processing systems – Information exchange between systems – Synchronous transmission signal quality at DTE/DCE interfaces ISO/IEC 9545:1994 Information technology – Open Systems Interconnection – Application Layer structure ISO/TR 9547:1988 Programming language processors - Test methods - Guidelines for their development and acceptability ISO/IEC 9548 Information technology – Open Systems Interconnection – Connectionless Session protocol ISO/IEC 9548-1:1996 Protocol specification ISO/IEC 9548-2:1995 Protocol Implementation Conformance Statement (PICS) proforma ISO/IEC 9549:1990 Information technology – Galvanic isolation of balanced interchange circuit ISO 9555 Measurement of liquid flow in open channels – Tracer dilution methods for the measurement of steady flow ISO 9555-1:1994 Part 1: General ISO 9555-3:1992 Part 3: Chemical tracers ISO 9555-4:1992 Part 4: Fluorescent tracers ISO 9564 Financial services – Personal Identification Number (PIN) management and security ISO 9568:1993 Cinematography – Background acoustic noise levels in theatres, review rooms and dubbing rooms ISO/IEC TR 9573:1988 Information processing - SGML support facilities - Techniques for using SGML ISO/IEC TR 9573-11:2004 Part 11: Structure descriptions and style specifications for standards document interchange ISO/IEC TR 9573-13:1991 Part 13: Public entity sets for mathematics and science ISO/IEC 9574:1992 Information technology – Provision of the OSI connection-mode network service by packet mode terminal equipment to an integrated services digital network (ISDN) ISO/IEC TR 9575:1995 Information technology – Telecommunications and information exchange between systems – OSI Routeing Framework ISO/IEC 9576 Information technology – Open Systems Interconnection – Connectionless Presentation protocol ISO/IEC 9576-1:1995 Protocol specification ISO/IEC 9576-2:1995 Protocol Implementation Conformance Statement (PICS) proforma ISO/IEC TR 9577:1999 Information technology – Protocol identification in the network layer ISO/IEC TR 9578:1990 Information technology – Communication interface connectors used in local area networks ISO/IEC 9579:2000 Information technology – Remote database access for SQL with security enhancement ISO 9583:1993 Implants for surgery – Non-destructive testing – Liquid penetrant inspection of metallic surgical implants ISO 9584:1993 Implants for surgery – Non-destructive testing – Radiographic examination of cast metallic surgical implants ISO 9585:1990 Implants for surgery – Determination of bending strength and stiffness of bone plates ISO/IEC 9592 Information technology – Computer graphics and image processing – Programmer's Hierarchical Interactive Graphics System (PHIGS) ISO/IEC 9593 Information technology – Computer graphics – Programmer's Hierarchical Interactive Graphics System (PHIGS) language bindings ISO/IEC 9594 Information technology – Open Systems Interconnection – The Directory ISO/IEC 9594-1:2017 Part 1: Overview of concepts, models and services ISO/IEC 9594-2:2017 Part 2: Models ISO/IEC 9594-3:2017 Part 3: Abstract service definition ISO/IEC 9594-4:2017 Part 4: Procedures for distributed operation ISO/IEC 9594-5:2017 Part 5: Protocol specifications ISO/IEC 9594-6:2017 Part 6: Selected attribute types ISO/IEC 9594-7:2017 Part 7: Selected object classes ISO/IEC 9594-8:2017 Part 8: Public-key and attribute certificate frameworks ISO/IEC 9594-9:2017 Part 9: Replication ISO/IEC 9595:1998 Information technology – Open Systems Interconnection – Common management information service ISO/IEC 9596 Information technology – Open Systems Interconnection – Common management information protocol ISO/IEC 9596-1:1998 Part 1: Specification ISO/IEC 9596-2:1993 Protocol Implementation Conformance Statement (PICS) proforma ISO 9611:1996 Acoustics – Characterization of sources of structure-borne sound with respect to sound radiation from connected structures – Measurement of velocity at the contact points of machinery when resiliently mounted ISO 9613 Acoustics – Attenuation of sound during propagation outdoors ISO 9613-1:1993 Part 1: Calculation of the absorption of sound by the atmosphere ISO 9613-2:1996 Part 2: General method of calculation ISO 9614 Acoustics – Determination of sound power levels of noise sources using sound intensity ISO 9614-1:1993 Part 1: Measurement at discrete points ISO 9614-2:1996 Part 2: Measurement by scanning ISO 9614-3:2002 Part 3: Precision method for measurement by scanning ISO 9626:2016 Stainless steel needle tubing for the manufacture of medical devices – Requirements and test methods ISO/IEC 9636 Information technology - Computer graphics - Interfacing techniques for dialogues with graphical devices (CGI) - Functional specification ISO/IEC 9636-1:1991 Part 1: Overview, profiles, and conformance ISO/IEC 9636-2:1991 Part 2: Control ISO/IEC 9636-3:1991 Part 3: Output ISO/IEC 9636-4:1991 Part 4: Segments ISO/IEC 9636-5:1991 Part 5: Input and echoing ISO/IEC 9636-6:1991 Part 6: Raster ISO/IEC 9637 Information technology - Computer graphics - Interfacing techniques for dialogues with graphical devices (CGI) – Data stream binding ISO/IEC 9637-1:1994 Part 1: Character encoding ISO/IEC 9637-2:1992 Part 2: Binary encoding ISO/IEC 9638 Information technology - Computer graphics - Interfacing techniques for dialogues with graphical devices (CGI) - Language bindings ISO/IEC 9638-3:1994 Part 3: Ada ISO 9645:1990 Acoustics – Measurement of noise emitted by two-wheeled mopeds in motion – Engineering method ISO/IEC 9646 Information technology—Open Systems Interconnection—Conformance testing methodology and framework ISO/IEC 9646-1:1994 Part 1: General concepts ISO/IEC 9646-2:1994 Part 2: Abstract Test Suite specification ISO/IEC 9646-3:1998 Part 3: The Tree and Tabular Combined Notation (TTCN) ISO/IEC 9646-4:1994 Part 4: Test realization ISO/IEC 9646-5:1994 Part 5: Requirements on test laboratories and clients for the conformance assessment process ISO/IEC 9646-6:1994 Part 6: Protocol profile test specification ISO/IEC 9646-7:1995 Part 7: Implementation Conformance Statements ISO 9660:1988 Information processing – Volume and file structure of CD-ROM for information interchange ISO/IEC 9661:1994 Information technology – Data interchange on 12,7 mm wide magnetic tape cartridges – 18 tracks, 1 491 data bytes per millimetre ISO 9662:1994 Aircraft equipment - Environmental and operating conditions for airborne equipment - Humidity, temperature and pressure tests ISO 9668:1990 Pulps — Determination of magnesium content — Flame atomic absorption spectrometric method [Withdrawn: replaced with ISO 12830] ISO 9687:2015 Dentistry - Graphical symbols for dental equipment ISO 9688:1990 Mechanical vibration and shock – Analytical methods of assessing shock resistance of mechanical systems – Information exchange between suppliers and users of analyses ISO 9696:2007 Water quality - Measurement of gross alpha activity in non-saline water - Thick source method ISO 9706:1994 Information and documentation – Paper for documents – Requirements for permanence ISO 9707:2008 Information and documentation - Statistics on the production and distribution of books, newspapers, periodicals and electronic publications ISO 9712:2012 Non-destructive testing - Qualification and certification of NDT personnel ISO 9713:2002 Neurosurgical implants – Self-closing intracranial aneurysm clips ISO 9714 Orthopaedic drilling instruments ISO 9714-1:2012 Part 1: Drill bits, taps and countersink cutters ISO 9735:1988 Electronic data interchange for administration, commerce and transport (EDIFACT) – Application level syntax rules (Syntax version number: 4, Syntax release number: 2) ISO 9735-1:2002 Part 1: Syntax rules common to all parts ISO 9735-2:2002 Part 2: Syntax rules specific to batch EDI ISO 9735-3:2002 Part 3: Syntax rules specific to interactive EDI ISO 9735-4:2002 Part 4: Syntax and service report message for batch EDI (message type – CONTRL) ISO 9735-5:2002 Part 5: Security rules for batch EDI (authenticity, integrity and non-repudiation of origin) ISO 9735-6:2002 Part 6: Secure authentication and acknowledgement message (message type – AUTACK) ISO 9735-7:2002 Part 7: Security rules for batch EDI (confidentiality) ISO 9735-8:2002 Part 8: Associated data in EDI ISO 9735-9:2002 Part 9: Security key and certificate management message (message type – KEYMAN) ISO 9735-10:2014 Part 10: Syntax service directories ISO/IEC 9796 Information technology – Security techniques – Digital signature schemes giving message recovery ISO/IEC 9796-2:2010 Part 2: Integer factorization based mechanisms ISO/IEC 9796-3:2006 Part 3: Discrete logarithm based mechanisms ISO/IEC 9797 Information technology – Security techniques – Message Authentication Codes (MACs) ISO/IEC 9797-1:2011 Part 1: Mechanisms using a block cipher ISO/IEC 9797-2:2011 Part 2: Mechanisms using a dedicated hash-function ISO/IEC 9797-3:2011 Part 3: Mechanisms using a universal hash-function ISO/IEC 9798 Information technology – Security techniques – Entity authentication ISO/IEC 9798-1:2010 Part 1: General ISO/IEC 9798-2:2008 Part 2: Mechanisms using symmetric encipherment algorithms ISO/IEC 9798-3:1998 Part 3: Mechanisms using digital signature ISO/IEC 9798-4:1999 Part 4: Mechanisms using a cryptographic check function ISO/IEC 9798-5:2009 Part 5: Mechanisms using zero-knowledge techniques ISO/IEC 9798-6:2010 Part 6: Mechanisms using manual data transfer ISO 9801:2009 Ophthalmic instruments – Trial case lenses ISO 9802:1996 Raw optical glass – Vocabulary ISO/IEC 9804:1998 Information technology – Open Systems Interconnection – Service definition for the Commitment, Concurrency and Recovery service element ISO/IEC 9805 Information technology – Open Systems Interconnection – Protocol for the Commitment, Concurrency and Recovery service element ISO/IEC 9805-1:1998 Protocol specification ISO/IEC 9805-2:1996 Protocol Implementation Conformance Statement (PICS) proforma ISO/TR 9824:2007 Hydrometry – Measurement of free surface flow in closed conduits ISO 9825:2005 Hydrometry – Field measurement of discharge in large rivers and rivers in flood ISO 9826:1992 Measurement of liquid flow in open channels – Parshall and SANIIRI flumes ISO 9827:1994 Measurement of liquid flow in open channels by weirs and flumes – Streamlined triangular profile weirs ISO/IEC 9834 Information technology – Open Systems Interconnection – Procedures for the operation of OSI Registration Authorities ISO/IEC 9834-1:2012 General procedures and top arcs of the international object identifier tree ISO/IEC 9834-2:1993 Part 2: Registration procedures for OSI document types ISO/IEC 9834-3:2008 Registration of Object Identifier arcs beneath the top-level arc jointly administered by ISO and ITU-T ISO/IEC 9834-4:1991 Part 4: Register of VTE Profiles ISO/IEC 9834-5:1991 Part 5: Register of VT Control Object Definitions ISO/IEC 9834-6:2005 Registration of application processes and application entities ISO/IEC 9834-7:2008 Joint ISO and ITU-T Registration of International Organizations ISO/IEC 9834-8:2014 Part 8: Generation of universally unique identifiers (UUIDs) and their use in object identifiers ISO/IEC 9834-9:2008 Registration of object identifier arcs for applications and services using tag-based identification ISO 9846 Solar energy -- Calibration of a pyranometer using a pyrheliometer ISO 9847 Solar energy -- Calibration of field pyranometers by comparison to a reference pyranometer ISO 9849:2017 Optics and optical instruments - Geodetic and surveying instruments - Vocabulary ISO 9851:1990 Continuous mechanical handling equipment – Overhead electrical monorail conveyors – Definitions and safety rules ISO 9869 Thermal insulation – Building elements – In-situ measurements of thermal resistance and thermal transmittance ISO 9873:2017 Dentistry - Intra-oral mirrors ISO 9878:1990 Micrographics - Graphical symbols for use in microfilming ISO 9897:1997 Freight containers - Container equipment data exchange (CEDEX) - General communication codes ISO/IEC 9899:2018 Programming languages – C ISO 9902 Textile machinery – Noise test code ISO 9902-1:2001 Part 1: Common requirements ISO 9902-2:2001 Part 2: Spinning preparatory and spinning machinery ISO 9902-3:2001 Part 3: Nonwoven machinery ISO 9902-4:2001 Part 4: Yarn processing, cordage and rope manufacturing machinery ISO 9902-5:2001 Part 5: Weaving and knitting preparatory machinery ISO 9902-6:2001 Part 6: Fabric manufacturing machinery ISO 9902-7:2001 Part 7: Dyeing and finishing machinery ISO 9926 Cranes – Training of operators ISO 9926-1:1990 Part 1: General ISO 9926-3:2016 Part 3: Tower cranes ISO/IEC/IEEE 9945:2009 Information technology – Portable Operating System Interface (POSIX®) Base Specifications, Issue 7 ISO 9947:2005 Textile machinery and accessories – Two-for-one twisters – Vocabulary ISO 9949 Urine absorbing aids - Vocabulary ISO 9949-1:1993 Part 1: Conditions of urinary incontinence ISO 9949-2:1993 Part 2: Products ISO 9949-3:1993 Part 3: Identification of product types ISO 9951:1993 Measurement of gas flow in closed conduits – Turbine meters ISO 9957 Fluid draughting media ISO 9957-1:1992 Part 1: Water-based India ink – Requirements and test conditions ISO 9957-2:1995 Part 2: Water-based non-India ink – Requirements and test conditions ISO 9957-3:1997 Part 3: Water-based coloured draughting inks – Requirements and test conditions ISO 9958 Draughting media for technical drawings – Draughting film with polyester base ISO 9958-1:1992 Part 1: Requirements and marking ISO 9958-2:1992 Part 2: Determination of properties ISO 9959 Numerically controlled draughting machines – Drawing test for the evaluation of performance ISO 9959-1:1992 Part 1: Vector plotters ISO 9960 Draughting instruments with or without graduation ISO 9960-1:1992 Part 1: Draughting scale rules ISO 9961:1992 Draughting media for technical drawings – Natural tracing paper ISO 9962 Manually operated draughting machines ISO 9962-1:1992 Part 1: Definitions, classification and designation ISO 9962-2:1992 Part 2: Characteristics, performance, inspection and marking ISO/IEC 9973:2013 Information technology - Computer graphics, image processing and environmental data representation - Procedures for registration of items ISO 9984:1996 Information and documentation – Transliteration of Georgian characters into Latin characters ISO 9985:1996 Information and documentation – Transliteration of Armenian characters into Latin characters ISO 9992 Financial transaction cards – Messages between the integrated circuit card and the card accepting device ISO/IEC 9995 Information technology – Keyboard layouts for text and office systems ISO 9997:1999 Dental cartridge syringes ISO 9999 Assistive products for persons with disability – Classification and terminology
Newsom supports a series of tentative water-sharing agreements that would bring an end to the dispute between farmers, cities, fishers, and environmentalists over how much water should be left in the state's two most important rivers, the Sacramento and San Joaquin, which flow into the Delta.
Sources: en.wikipedia.org
=== Depiction === The Combine comprises various species and machines. The most commonly encountered enemies throughout Half-Life 2 and its episodic sequels are the transhuman soldiers and human Civil Protection officers. In addition, a variety of combat machines appear, ranging from APCs and helicopter gunships to a giant 'smart wall' enclosing occupied cities and gradually destroying anything in its path, as well as a number of weaponized alien 'synths'.
where xH is amount of isotope xH. Fractional abundance is equivalent to mole fraction, and yields atom percent when multiplied by 100. In some instances atom percent excess is used, which reports the atom percent of a sample minus the atom percent of a standard.
Genes are arranged linearly along long chains of DNA base-pair sequences. In bacteria, each cell usually contains a single circular genophore, while eukaryotic organisms (such as plants and animals) have their DNA arranged in multiple linear chromosomes. These DNA strands are often extremely long; the largest human chromosome, for example, is about 247 million base pairs in length. The DNA of a chromosome is associated with structural proteins that organize, compact, and control access to the DNA, forming a material called chromatin; in eukaryotes, chromatin is usually composed of nucleosomes, segments of DNA wound around cores of histone proteins. The full set of hereditary material in an organism (usually the combined DNA sequences of all chromosomes) is called the genome. DNA is most often found in the nucleus of cells, but Ruth Sager helped in the discovery of nonchromosomal genes found outside of the nucleus. In plants, these are often found in the chloroplasts and in other organisms, in the mitochondria. These nonchromosomal genes can still be passed on by either partner in sexual reproduction and they control a variety of hereditary characteristics that replicate and remain active throughout generations. While haploid organisms have only one copy of each chromosome, most animals and many plants are diploid, containing two of each chromosome and thus two copies of every gene. The two alleles for a gene are located on identical loci of the two homologous chromosomes, each allele inherited from a different parent.
=== 2000s === 2001: spins off its Microelectronics Division (30% of its revenue), that becomes Mykrolis, which will merge with Entegris in 2005 2002: opens Biopharmaceutical Technology Center in Billerica, Massachusetts 2005: acquires MicroSafe, a European contract testing laboratory 2005: acquires NovAseptic, supplier of aseptically designed components for biotech and pharmaceutical production 2005: forms alliance with Gen-Probe to develop, manufacture and commercialize products for rapid microbiological and virus monitoring 2006: acquires Newport Bio Systems, a maker of process containers and systems used in biopharmaceutical production 2006: acquires Serologicals Corporation (including the companies Chemicon, Upstate, Linco, and Celliance), expanding its drug discovery and development footprint 2006: opens a new Research and Development Center in Bedford, Massachusetts 2007: launches its new brand 2008: expands drug discovery and development facility in St. Charles, Missouri 2008: opens membrane casting manufacturing facility in Carrigtwohill, County Cork, Ireland 2009: acquires Guava Technologies, a provider of bench top cell analysis systems 2009: opens Biomanufacturing Sciences and Training Center in Singapore 2009: acquires BioAnaLab, a European-based firm specializing in the analysis of biologic drugs and vaccines 2010: Merck KGaA acquires Millipore, which will be part of the EMD Group 2015: Merck completes $17 billion acquisition of Sigma-Aldrich, combining EMD Millipore and Sigma-Aldrich to create life science company MilliporeSigma
Sources: en.wikipedia.org
It is a synthetic peptide of 31 amino acids, built to resemble the natural incretin hormone GLP-1. Because of its size and composition it is handled analytically like other therapeutic peptides, using chromatographic and mass spectrometric methods rather than the techniques typical of small organic drugs.
The substitution at position 8 removes the site recognised by dipeptidyl peptidase-4, the enzyme that destroys the native hormone within minutes. The linked lipophilic chain then binds circulating albumin, which further limits access by degradative enzymes and reduces renal loss. Together these features lengthen the effective circulation time considerably.
It acts at the glucagon-like peptide-1 receptor, a G protein-coupled receptor that signals mainly through cyclic AMP. Activation is glucose dependent, meaning insulin release is stimulated more strongly when blood glucose is already elevated. Other tissues carrying the same receptor respond as well, which explains effects beyond glucose control.
冻融过程中冰晶形成与局部浓度升高会促使肽链发生界面吸附和聚集。聚集不仅降低有效含量,还会改变可见异物与不溶性微粒的计数结果。将溶液分装为单次使用的小体积等份可减少循环次数。