Strategies for the Development Biomarkers Application to Lung Cancer Early Detection
产品战略分析英语作文
产品战略分析英语作文Product Strategy Analysis。
Introduction:In today's competitive business environment, having an effective product strategy is crucial for the success of any organization. A product strategy defines the direction and goals for a company's products, ensuring that they meet the needs and expectations of the target market. This essay aims to analyze the importance of product strategy and its impact on the overall success of a company.Body:1. Understanding the Market:A successful product strategy begins with a deep understanding of the target market. This involves conducting market research to identify customer needs,preferences, and trends. By analyzing the market, companies can identify gaps and opportunities that can be capitalized on through innovative product development. Understanding the market is the foundation of a strong product strategy.2. Setting Clear Objectives:Once the market has been analyzed, it is essential to set clear objectives for the product strategy. These objectives should align with the overall business goals and be specific, measurable, attainable, relevant, and time-bound (SMART). Setting clear objectives helps in guiding the product development process and measuring the success of the strategy.3. Differentiation and Competitive Advantage:In a crowded marketplace, differentiation is key to stand out from the competition. A well-defined product strategy should focus on creating a unique value proposition that sets the product apart from competitors. This can be achieved through product features, quality,pricing, branding, or customer service. By offering something distinct, companies can gain a competitive advantage and attract a loyal customer base.4. Product Lifecycle Management:Another important aspect of product strategy is managing the product lifecycle effectively. Products go through various stages, including introduction, growth, maturity, and decline. Understanding the lifecycle helps in making informed decisions regarding product improvements, updates, or discontinuation. By managing the product lifecycle, companies can maximize profitability andmaintain customer satisfaction.5. Continuous Innovation:Innovation is the lifeblood of a successful product strategy. Customers' needs and preferences evolve over time, and companies must adapt to these changes. A productstrategy should include a focus on continuous innovation to stay ahead of the competition and meet changing customerdemands. This can involve research and development, product enhancements, or even introducing entirely new products to the market.6. Marketing and Communication:An effective product strategy is incomplete without a well-executed marketing and communication plan. Once the product is developed, it is crucial to create awareness, generate interest, and persuade customers to make a purchase. This requires effective marketing campaigns, advertising, public relations, and customer engagement. A strong marketing and communication plan ensures that the target market is aware of the product's benefits and encourages them to choose it over competitors.Conclusion:In conclusion, a well-defined product strategy is essential for the success of any organization. It helps companies understand the market, set clear objectives, differentiate from competitors, manage the productlifecycle, foster continuous innovation, and effectively market the product. By implementing a strong product strategy, companies can increase their chances of success in the highly competitive business landscape.。
Strategies for the Production of Recombinant Protein in Escherichia coli
Strategies for the Production of Recombinant Protein in Escherichia coliGopal Jee Gopal •Awanish KumarPublished online:30July 2013ÓSpringer Science+Business Media New York 2013Abstract In the recent past years,a large number of proteins have been expressed in Escherichia coli with high productivity due to rapid development of genetic engi-neering technologies.There are many hosts used for the production of recombinant protein but the preferred choice is E.coli due to its easier culture,short life cycle,well-known genetics,and easy genetic manipulation.We often face a problem in the expression of foreign genes in E.coli .Soluble recombinant protein is a prerequisite for structural,functional and biochemical studies of a protein.Researchers often face problems producing soluble recombinant proteins for over-expression,mainly the expression and solubility of heterologous proteins.There is no universal strategy to solve these problems but there are a few methods that can improve the level of expression,non-expression,or less expression of the gene of interest in E.coli .This review addresses these issues properly.Five levels of strategies can be used to increase the expression and solubility of over-expressed protein;(1)changing the vector,(2)changing the host,(3)changing the culture parameters of the recombinant host strain,(4)co-expres-sion of other genes and (5)changing the gene sequences,which may help increase expression and the proper folding of desired protein.Here we present the resources available for the expression of a gene in E.coli to get a substantial amount of good quality recombinant protein.The resources include different strains of E.coli ,different E.coliexpression vectors,different physical and chemical agents and the co expression of chaperone interacting proteins.Perhaps it would be the solutions to such problems that will finally lead to the maturity of the application of recombi-nant proteins.The proposed solutions to such problems will finally lead to the maturity of the application of recombi-nant proteins.Keywords E.coli ÁRecombinant protein expression ÁVector ÁHost cell Abbreviation aa Amino acid bp Base pairs GST Glutathione S-transferase HAT Histone acetyltransferase IPTG Isopropylthio-b -galactoside MBP Maltose binding protein NEB New England Biolabs MCS Multiple cloning siteNi-NTA Nickel nitrilotriacetic acid ORF Open reading frame SUMO Small ubiquitin modifier Trx Thioredoxin1IntroductionThere are many hosts used for the production of recom-binant protein,but the preferred choice is Escherichia coli because it is easy to culture,has a very short life cycle and is easily manipulated genetically due to its well-known genetics. E.coli was the first host used to produce a recombinant DNA (rDNA)biopharmaceutical,enablingG.J.GopalSchool of Biotechnology,Jawaharlal Nehru University,New Delhi 110067,IndiaA.Kumar (&)Department of Biotechnology,National Institute of Technology,Raipur 492010,Chhattisgarh,India e-mail:drawanishkr@Protein J (2013)32:419–425DOI 10.1007/s10930-013-9502-5the approval of Eli Lilly’s rDNA human insulin in1982. We also use E.coli host often to produce therapeutic protein to minimize the cost of production.In E.coli,we face two main problems;(1)is difficult or little expression of a foreign gene and(2)is solubility of recombinant proteins for over expression.Structural,functional and biochemical studies of protein requires an ample amount of good quality protein.There is no universal strategy to solve this problem but there are a few methods that can improve the level of expression or non-expression or decreasedexpression of a gene of interest in E.coli.Factors such as mRNA’s secondary structure,a protein’s intrinsic ability to fold,its solubility,preferential codon use,its toxicity,and its need for post translational modification have influence on expression of foreign gene in E.coli[27].At least four strategies can useful for increasing the expression and solubility of over-expressed protein;Changing the vector, changing the host strain,and adding of some chemicals during the induction or co-expression of other genes may help in the proper folding of the desired protein.If the above strategies are unsuccessful,then one can alter the gene sequence without changing the functional domain. Gene sequence alteration include the removal of a signal peptide coding sequence,optimisation of codon according to E.coli,deletion of hydrophobic patch coding sequences, and prevention of stable mRNA secondary structure for-mation by changing the sequence which forms secondary structure etc.The main focus of this review is to describe various strategies for the expression of foreign genes/pro-teins in E.coli with minimum difficulty.This review highlights the problem encountered problems and knowl-edge gained during widespread research on proteins expression and production.2Strategies for Over Expression of Foreign Gene and Production of Recombinant Protein2.1Changing the VectorChanging the vector refers to either changing the promoter with which the gene of interest is to be cloned or changing the fusion‘tag’which influence solubilization of recom-binant protein in E.coli host(Table1).The pET vector with6-Histidine tag(His-tag),is usually thefirst choice to get recombinant protein because His-tag is a smaller affinity tag with high levels of expression due to the presence of a strong promoter and the availability of robust purification system like Ni-NTA.The pET vector is pro-vided by‘Novagen’.Consecutive6-Histidine can possibly decrease the solubility of a fused protein.If consecutive Histidine poses a problem in the solubility of a protein, pHAT vector can be used.The pET vector is commercially provided by‘Clontech’,and encodes a novel polyhistidine epitope tag.This tag is19amino acids long and has a non adjacent6-Histidine.This sequence of nonadjacent histi-dine residues has a lower overall charge than tags with consecutive histidine residues.As a result,HAT fusion proteins exhibit solubility close to wild-type proteins without compromising the affinity for metal.When a histidine tagged gene does not express the protein or recombinant protein forms inclusion bodies,the gene of interest should be cloned in pGEX system of‘GE healthcare’or GST tag,or in pMAL system of‘New England Biolabs’.It has been well established that maltose binding protein(MBP)tag[3,7,12]and GST tag[31] increases solubility of fused proteins and expression of genes.The drawback of pMAL system and pGEX vector is their large sizes of fusion tag(MBP:44kDa;GST: 25kDa).The large size of fusion tags may interfere with the activity of recombinant proteins if the tag is not cleaved properly.Different enzyme sites have been incorporated in this vector so that cleavage would be precise and no extra amino acid remain fused with recombinant protein.Tags may interfere with the structure and function of the target protein,therefore provision tags must be removed after the expression and purification of the protein.Multiple cleav-age sites can be engineered into the expression construct to remove tags.Enterokinase(cleavage site DDDDK:),Fac-tor Xa(cleavage site IEGR:),SUMO protease(recognizes SUMO tertiary structure and cleaves at the C-terminal end of the conserved Gly–Gly sequence in SUMO),Thrombin (cleavage site LVPR:GS)are the common proteases used to remove tags often from recombinant protein(Table1). Three variations of pMAL vector are available with NEB based on enzyme cleavage site:factor Xa,genenase, enterokinase classified as P/C5X,P/C5G,and P/C5E respectively.C and P indicate cytoplasmic or periplasmic expression respectively.SUMO tag recombinant protein has a tendency to be soluble in the E.coli host[2].pSUMO vector with kanamycine and ampiciline resistance marker available.pSUMO vector with dual expression(E.coli/ yeast and E.coli/mammalian cell)and only bacterial expression is also commercially available from‘LifeSen-sors Inc.,271,Great Valley Parkway’.One big advantage of using pSUMO vector is the ability to get recombinant Table1Some common tags used in enhancing protein solubility Tag Protein Size GST Glutathione S-transferase211aa MBP Maltose-binding protein396aa NusA N-utilization substance495aa Sumo Small ubiquitin modifier100aa Trx Thioredoxin109aa420G.J.Gopal,A.Kumarprotein without any extra amino acid after cleavage of the tag by SUMO protease.N-utilization substance A(NusA) tag also increases solubility of the tagged protein.Solu-bility modeling of E.coli protein shows that NusA tag has the highest potential for solubility[4,11].pET-43and pET-44vectors supplied by‘Novagen’can be used for NusA tagged recombinant protein.Fusion of109-aa long Trx.tag thioredoxin protein also increases the solubility of conjugated protein.The pET-Trx plasmid vector can be used for this tag[16,24].pET-39b and pET-40b plasmid are used to conjugate208aa DsbA and236aa DsbC proteins involved in periplasmic disulphide bond formation respectively.DsbA helps in the formation of disulphide bond and DsbC assists in the isomerization of disulphide bond.The recombinant protein(s)conjugated with this protein tag can form disulphide bond in E.coli[10,11,14, 23,35].Fusion tags like NusA,Trx and SUMO needs extra affinity tag for purification.The main disadvantage of NusA,Trx,and SUMO is their requirement for extra affinity tag for protein purification[23].pQE system of Qiagen(containing T5promoter)has been shown to increase expression of gene but it does not express with T7promoter.T5promoter is recognised by E.coli polymerase and it has two lac operator sequences. The presence of these two lac operator sequence increase the lac repressor binding and ensure for the sufficient repression of proteins.This vector has6-His tag at the–N or–C terminal and is suitable for the expression in E.coli host strains like,M15[pREP4]and SG13009[pREP4]. These strains contain pREP4plasmid.This plasmid encodes lac repressor which ensures tight regulation of expression.Sometimes periplasmic translocation of gene products can be required for proper folding and/or disul-phide bond formation or for easy purification.To fulfil these requirement,there are also plasmid variants are available with E.coli signal peptide coding sequences at the50of MCS like p5series(c5series is for cytoplasmic expression)of pMAL vector,pET-22vector etc.Solubility of recombinant protein in E.coli can be determined or checked with freely available software by conjugating the sequence of the fusion tag with the desired protein sequence.This exercise may be useful before cloning the gene of interest.It is also important to search common cloning sites for different vectors before designing the primers.This allows the desired gene fragment to be sub-cloned from one vector to other without purchasing new primer pairs and without PCR amplification of insert using new primer sets.A vector should be chosen in such a way with consideration that the tag increase solubility but does not disrupt the activity of the recombinant protein or the cleavage of the tag.It has also been observed(personal observation)that non expression of gene is due to frame shift in the reading frame during cloning which causes stop codon incorporation.New researchers could prevent this during cloning at the NcoI restriction endonuclease site of pET-28a plasmid.Cloning at NcoI site in this vector requires two extra base pair in the primer sequence at50to amplify open reading frame(ORF).2.2Changing the Host StrainNowadays so many biotech companies provide different types of genetically altered E.coli strain as per suitability of expression of foreign genes(Table2).Genes cloned with‘tac’promoter(pMAL system,pGEX system)can be expressed in the cloning host itself but the BL21strain is the preferred choice for expression because of absence of two main proteases genes cloned in pET system with T7 promoter should be expressed in BL21(DE3).E.coli strain BL21(DE3)has a T7polymerase encoding gene introduced in its genome as well as Lon and OmpT protease deleted. Lon and OmpT protease deficient strain of E.coli are unable to degrade foreign protein.Leaky expression of the desired gene in BL21(DE3)cell is possible.To minimise leaky expression of toxic gene,the BL21host strain was improved.The improved strain is BL21(DE3)pLys S and BL21(DE3)pLys E.Both the strain have lysozyme coding plasmid.Lysozyme is inhibitor of T7polymerases which inhibits residual T7polymerase and thus prevents leaky expression.Leaky expression of toxic gene is detrimental to the host cell—the host cell will not survive or it will change its mechanism so that even in presence of inducer it will not allow production of toxic protein.Many times expression does not occur in E.coli due to a difference in codons present in gene of interest and preferential codon use by the host E.coli strain.To solve this codon bias in host cell machinery,a few companies provide modified E.coli hosts that have extra tRNA coding genes(AUA, AGG,AGA,CUA,CCC and GGA)compensating for the scarcity of rare tRNA(Fig.1).The host strain is designed as CodonPlus E.coli strain of‘Stratagene’(RIL or RP)and Rosetta strain(Novagene).Rosetta host strains are BL21(DE3)derivatives designed to enhance the expression of heterologous proteins by containing codons rarely used in E.coli.CodonPlus-RIL strain is used to overcome the bias of AT-rich genome while CodonPlus-RP strain is used to overcome GC rich genome bias.Unlike CodonPlus of Stratagene,the Rosetta strain contains all the genes coding rare tRNA in the same strain so separate strain for AT and GC rich gene expression would need to be used.Ori-gami TM E.coli strain of‘Novagene’may be used if disulphide bond is required for proper folding of protein. The Origami strain is an oxidising E.coli strain with mutation in thioredoxin reductase(trxB)and glutathione reductase(gor)genes that allows disulphide bond forma-tion within cytoplasm.‘SHuffle’E.coli strains from‘NEB’Production of Recombinant Protein421are better than‘Origami’strain for the expression of putative disulphide bond forming protein.In addition to trxB and gor mutation,SHuffle strains express DsbC within the cytoplasm,which directs correct disulfide bond for-mation and also acts as a general chaperone for protein folding.For the expression of gene which coding globular or membrane protein,C43(DE3)strain of E.coli[1]provided by Lucigen can be used.C41(DE3)and C43(DE3)strain(walker strain)are also useful in overcoming the problem of plasmid instability during toxic recombinant protein expression[15]. Walker strain is derivative of BL21(DE3).Membrane protein overexpression characteristics of these strains are due to a mutation in lac UV5promoter which causing weaker expression of T7RNA polymersae.Lemo21(DE3)E.coli strain from‘NEB’is more improved host for the expression of gene cloned under T7promoter.The concept of Lemo21(DE3)strain came after the discloser of C43(DE3) and C41(DE3)strain’s genetic makeup[29].Lemo21(DE3) is derivative of BL21(DE3)strain and are genetically engi-neered in such manner that it can act as C43(DE3)self mutant strain[28].T7polymerase is cloned with the well-titrable rhamnose promoter and its activity can be precisely controlled by its natural inhibitor T7lysozyme found in this strain[34]. Using this Lemo21(DE3)strain,it has also been shown that Sec-translocon saturation is the main bottleneck for heterol-ogous membrane protein production[28].This strain is also used for the expression of difficult proteins such as membrane protein,toxic protein or the protein that aggregates in E.coli without compromising their stability and function[28,29]. Theflexibility of this strain makes it potent,time-saving and cost-effective to identify the optimal conditions for the overexpression of protein of interest.High level expression usually causes formation of an inclusion body.One way to avoid or decrease the inclusion body formation is to reduce cultivation temperature of the host after induction.However at low the temperature,the expression of chaperonine,which fold newly synthesized or misfolded protein,also reduce drastically.ArcticExpress strains of E.coli overcome this problem because these genetically engineered strain co-express cold-adapted chaperonins Cpn10and Cpn60from the psychrophilic bacterium,Oleispira antarctica.Chaperonine has high protein folding activity at4–10°C.This strain is com-mercially available from Agilent technology,Genomics. Acetylated recombinant protein has also been produced in genetically engineered E.coli strain but these strains are not commercially available.A high yield of protein also depends on the stability of corresponding mRNA.A BL21 derivative having an rne131mutation confers higher sta-bility of mRNA and ultimately increased gene expression. This strain is available from Invitrogen under the name BL21Star[10,13,18,19].Glycosylated recombinant protein has been produced from genetically engineeredTable2Characteristics of E.coli strains used in recombinant protein expressionE.coli strain Used for Characteristics at genetic levelArcticExpress Grow at low temperature Low temperature adapted chaperone encoded gene BL21Less protease degradation of recombinantproteinLon and OmpT protease deficientBL21-Codonplus(RIL)Overcome the effect of codon biasness(AT richgene)tRNA encoding gene(argU,ileY and leuW)BL21(DE3)Expression under T7promoter T7pol encodedBL21(DE3)pLys S/E Controlled expression Lysozyme encoded plasmidBL21Star Increase stability of mRNA rne31gene mutatedC41(DE3)Overexpressing toxic proteins Carry the lambda DE3lysogen which expresses T7RNA polymerase from the lacUV5promoter byIPTG inductionC43(DE3)Membrane and globular protein-Same-Codon plus(RP)Overcome the effect of codon biasness(GC richgene)tRNA encoding gene(argU and proL)Lemo21(DE3)Membrane,globular and toxic protein expression Lysozyme encoded under rhamnose induciblepromoterM15Gene under T5promoter Constitutively expresses lac repressor at high levels Origami Protein required disulphide bond formation gor and trxB genes mutatedRossetta Both the AT and GC rich gene All the rare tRNA coding geneSG13009Enabling trans repression of protein expressionprior to IPTG induction Carry the repressor plasmid pREP4,which constitutively expresses lac repressor at high levelsShuffle Proper disulphide bond formation DsbC gene encoded422G.J.Gopal,A.KumarE.coli with the pgl operon of Campylobacter jejuni [22].This strain is not commercially available and the glyco-sylation pattern is different from that of eukaryote so it is not frequently used.N -linked protein glycosylation is the most common post-translational modification in eukary-otes.Recently,Valderrama-Rincon et al.[33]successfully engineered an E.coli strain and got N-glycosylation of eukaryotic recombinant protein.Strains of E.coli fre-quently used in recombinant protein production are shown and summarized in Fig.1.2.3Changing the Culture Parameters of RecombinantHost Strain Culture condition of recombinant E.coli may also increase expression of gene and solubility of expressed protein.The solubility of recombinant protein is increased by prolonged induction at low temperatures with decreased amounts of IPTG.Sometimes addition of some chemical in culture medium also increases expression of the gene of interest because these chemicals induce chaperone expression.Induced chaperone manages the proper folding of recom-binant protein and thus enables it to remain in soluble form.Expressed proteins may be stabilized by the binding with ligands (a small chemical agent)and have found widespread application in recombinant protein productions [9].This concept is exploited to increase the proportion of recombi-nant protein expressed in soluble form or to stabilize a protein during purification [10].Ethanol [8,14],heat shock i.e.temperature treatment [20],benzyl alcohol [5],osmo-lytes,ionic strength of buffer [6,30]etc.,are inducers that enhance expression and production of recombinant proteins.2.4Co-expressionFew proteins require their counterparts for their stability so the genes coding these protein either do not express or express and then degrade the counterparts immediately.In any case recombinant protein would not be produced.In this situation the interacting protein or protein which sta-bilizes the desired protein must be identified.The gene coding those proteins must be co-expressed with the pro-tein of interest.For example,chaperone,when co-expres-sed with gene of interest,increases the expression and solubility of that gene product.Recently deMarco,showed that when chaperone is co-expressed with a gene ofinterestFig.1 E.coli strains frequently used in recombinant protein production having different vector,promoter,multiple cloning sites,tRNA and other genesProduction of Recombinant Protein 423nearly all of the gene is expressed[5].Chaperone coding plasmid vectors are not commercially available but can be obtained by request from deMarco.When two gene product forms a complex,one gene alone is either expressed or not expressed but more importantly,forms inclusion bodies in the foreign host.This is due to exposed hydrophobic pat-ches in the absence of the interacting partner.The inter-acting partner of a complex protects the hydrophobic patches of both genes’proteins in the native environment. In this case,both genes should be co-expressed in heter-ologous host using either duet/bicistronic vector or two compatible vectors.Expression of toxin coding gene usu-ally requires the co-expression of an antitoxin coding gene or toxin gene with a mutated toxic region.2.5Changing Gene Sequences Without Changingthe Functional Domain of ProteinRemoval of signal peptide coding sequence also increases the expression and stability of recombinant protein.Signal peptides usually have no role except the export of protein from the site of synthesis to the target site.Therefore, endogenous mature protein does not have signal peptides. Production of recombinant protein without signal sequence in heterologous host would not alter its biochemical char-acteristics and function.Thus a signal peptide coding sequence can be removed from ORF if it hampers stability and expression of the complete ORF.Many times,the deletion of a transmembrane or hydrophobic patch coding region increases expression of the gene and solubility of the recombinant protein[26].To avoid codon bias in the heterologous host gene expression,the gene sequence can be optimized as per host preferences of the codon.Gene with optimized codon sequence can be obtained either through site directed mutagenesis(if a few codons have to be changed)or by synthesizing complete ORF.This opti-mized gene can then be cloned and expressed in the appropriate vector and host respectively.This optimised ORF does not require BL21-codon plus/Rossetta strain for its expression.The secondary structure of mRNA also hampers the efficient translation of a gene[25].To avoid the formation of this secondary structure,codon sequences can be manipulated via site directed mutagenesis without chang-ing the amino acid sequence[17].Gene sequence optimi-zation used to prevent the formation of mRNA secondary structure to smooth translation initiation and prolong mercial gene optimization services that optimize gene sequences and then synthesize that gene for efficient expression in a given host are also available. Usually gene optimization software consider following parameters:(a)Elimination of cryptic splice sites and RNA destabilizing sequence elements for increased RNA stability,(b)Addition of RNA stabilizing sequence ele-ments,(c)Codon optimization and G/C content adaptation for your expression system,(dld)Intron removal and avoidance of stable RNA secondary structures.3DiscussionThe methods for protein production and purification have been reviewed by researchers numerous times in an admirable and comprehensive manner.Here we have compiled the resources available till date for the production of ample and good quality recombinant protein using E.coli as a host.Production of recombinant protein in E.coli is less costly than using other hosts and the handling is also easier.Therefore,it is beneficial to utilize E.coli as a host for the production of desired protein.When recombinant protein is expressed immensely in bacteria,it tends to misfold and accumulate as a soluble and insoluble nonfunctional aggregate.A general strategy to improve the native folding of recombinant proteins is to increase the cellular concentration of viscous organic compounds, osmolytes,or of molecular chaperones that can prevent aggregation.If resources(as discussed above)are known to researchers then they can exploit that resource for their condition.Still there is no guarantee that all of the gene of interest will express in E.coli but researcher definitely will get most of the gene product by applying the aforemen-tioned strategy.Strategies for the expression of recombi-nant proteins in E.coli can be prioritized by changing the following factors(1)cultivation parameters,(2)host strain, (3)vector,(4)co-expression,(5)ORF with unaltered functional domain/structure(Fig.2).Priority can be chan-ged on the basis of known physiochemical properties of proteins.It is suggested to try these strategies in permu-tation to get overexpression of the gene/protein of interest.It would be beneficial to screen the solubility of recombinant protein through available in silico tools before cloning into particular vectors[32,36].To save time and resources it would be better to use an existing vector or host strain but if the existing vector or host strain does not fit to the research design then a host and/or vector can be constructed.A universal host or vector which allows all types of gene expression is required.Host strains with combination of two or more features like‘Rosetta-gami’strain allow disulphide bond formation and also prevent the effect of codon bias.ArcticExpress,RIL/RP strain of E.coli has the ability to allow the expression of heterolo-gous gene at low temperature as well as nullify the effect of rare codon in the gene[21].ArcticExpress codon plus and Rossetta-gami are the variants of ArchticExpress and Rossetta strains that are also commercially available from ‘Agilent Technologies’and from‘Novagene’respectively.424G.J.Gopal,A.KumarThey are suitable for avoiding codon bias as well as allowing disulphide bond formation during gene expres-sion.It would be ideal if one E.coli strain could possess all the characteristics required for heterologous gene expres-sion such as,disulphide bond formation,rare t-RNA,low temperature adapted chaperone,slow expression etc.The information described here can subsequently be combined and utilized to express protein in E.coli ,minimizing the current problems researchers face.Moreover,the detail described in this review regarding protein expression may eliminate barriers and allow for successful implementation and management of multi-parallel expression strategies.Based on the examples presented,it is evident that the discussed strategies have had a significant impact on recombinant protein expression in E.coli.This is of utmost importance in the future for enhancing production of recombinant proteins.Acknowledgments G.J.G.acknowledges the University Grant Commission (UGC),New Delhi,India for endowing him the 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J,Mattern MR,Tran H,Shoo J,Tan R,WeissSR,Butt TR (2005)J Struct Funct Genomics6:103–111Fig.2Strategise for production of recombinant proteins in E.coli .Buffers,pH,ionic strength,temperature,time etc.are the important factors and variables for easy and enhanced production of recombinant protein in E.coli .By following these expression strategies and manipulating these factors researcher could get rid of troubles during recombinant protein production studyProduction of Recombinant Protein 425。
Strategies_for_diversification[1]
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Strategies for Diversification
By H. Igor Ansoff
The Red Queen said, "Now, here, it takes all the running you can do to keep in the same place. If you want to get somewhere else, you must run at least twice as fast as that!" ^ So it is in the American economy. Just to retain its relative position, a business firm must go through continuous growth and change. To improve its position, it must grow and change at least "twice as fast as that." According to a recent survey of the ioo largest United States corporations from 1909 to 1948, few companies that have stuck to their traditional products and methods have grown in stature. The report concludes: "There is no reason to believe that those now at the top will stay there except as they keep abreast in the race of innovation and competition." ^ There are four basic growth alternatives open to a business. It can grow through increased market penetration, through market development, through product development, or through diversification. A company which accepts diversification as a part of its planned approach to growth undertakes the task of continually weighing and comparing the advantages of these four alternatives, selecting first one combination and then another, depending on the particular circumstances in long-range development planning. While they are an integral part of the over^ Lewis J. Carroll, Through the Looking-Glass (New York, The Heritage Press, 1941), p. 41. " A. D. H. Kaplan, Big Enterprise in a Competitive System (Washington, The Brookings Institution, 1954), p. 142.
生物利用度在药物发展过程中的意义英语作文
生物利用度在药物发展过程中的意义英语作文The Significance of Bioavailability in the Drug Development ProcessIntroductionBioavailability plays a crucial role in the development of pharmaceutical drugs. It refers to the degree and rate at which a drug reaches the systemic circulation and is available at the site of action. Understanding and optimizing the bioavailability of a drug is essential for ensuring its therapeutic efficacy and safety. In this article, we will explore the significance of bioavailability in the drug development process.Bioavailablity and Drug AbsorptionOne of the key factors determining the bioavailability of a drug is its absorption. Absorption refers to the process by which a drug enters the bloodstream from its site of administration. Factors such as drug solubility, permeability, and formulation can influence the absorption of a drug. For example, drugs that are poorly soluble or poorly permeable may have low bioavailability, leading to suboptimal therapy.Bioavailability and Drug DistributionAfter absorption, a drug is distributed throughout the body to its target tissues or organs. The distribution of a drug is influenced by factors such as protein binding, tissue permeability, and blood flow. Drugs that are highly bound to plasma proteins may have limited distribution and lower bioavailability. Understanding the distribution of a drug is important for optimizing its dosage and dosing regimen.Bioavailability and Drug MetabolismOnce a drug is absorbed and distributed, it undergoes metabolism in the liver and other tissues. Metabolism can modify the structure of a drug, making it more or less active. The bioavailability of a drug can be affected by its metabolism, as metabolites may have different pharmacokinetic properties than the parent drug. This can impact the efficacy and safety of a drug, highlighting the importance of considering metabolism in the drug development process.Bioavailability and Drug EliminationFinally, a drug is eliminated from the body through processes such as renal excretion, hepatic metabolism, and biliary excretion. The rate of elimination can affect the bioavailability of a drug, as drugs with a short half-life may require more frequent dosing to maintain therapeutic levels.Understanding the elimination of a drug is essential for optimizing its bioavailability and overall pharmacokinetics.Optimizing Bioavailability in Drug DevelopmentIn order to optimize the bioavailability of a drug, researchers can use various strategies during the drug development process. These include selecting appropriate drug formulations, enhancing drug solubility and permeability, and minimizing the impact of metabolism and elimination. By considering bioavailability early in the drug development process, researchers can design drugs with improved efficacy, safety, and patient compliance.ConclusionIn conclusion, bioavailability is a critical factor in the drug development process. Understanding and optimizing the bioavailability of a drug is essential for ensuring its therapeutic effectiveness and safety. By considering factors such as absorption, distribution, metabolism, and elimination, researchers can develop drugs with improved bioavailability and pharmacokinetic properties. Ultimately, by prioritizing bioavailability in drug development, researchers can enhance the quality and impact of pharmaceutical drugs.。
ICH Q8(中英文)
ICH Q8（中英文）blueski推荐[2009-12-20]出处：Julia的blog作者：不详INTERNATIONAL CONFERENCE ON HARMONISATION 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ICH Harmonised Tripartite Guideline ICH三方协调指南Pharmaceutical Development药物开发Q8Recommended for Adoption at Step 4 of the ICH Process on 10 November 2005 by the ICH Steering Committee ICH指导委员会2005年11月10日ICH第四阶段推荐采用This Guideline has been developed by the appropriate ICH Expert Working Group and has been subject to consultation by the regulatory parties, in accordance with the ICH Process. At Step 4 of the Process the final draft is recommended for adoption to the regulatory bodies of the European Union, Japan and USA. 本指南根据ICH规程由合适的ICH专家工作组起草并经向法规部门咨询。
在规程的第4步，建议欧洲共同体、日本和美国的药政部门采用其最终的草案。
TABLE OF CONTENTS目录1. INTRODUCTION简介 (1)1.1 Objective of the Guideline指南目的 (1)1.2 Scope范围 (1)2. PHARMACEUTICAL DEVELOPMENT药物开发 (1)2.1 Components of the Drug Product制剂产品的组分 (4)2.1.1 Drug Substance活性成分 (4)2.1.2 Excipients辅料 (4)2.2 Drug Product制剂 (5)2.2.1 Formulation Development配方开发 (5)2.2.2 Overages超量 (6)2.2.3 Physicochemical and Biological Properties物化和生化性质 (7)2.3 Manufacturing Process Development制造工艺开发 (7)2.4 Container Closure System容器系统 (9)2.5 Microbiological Attributes微生物属性 (9)2.6 Compatibility兼容性 (10)3. GLOSSARY术语 (11)1. INTRODUCTION 简介1.1 Objective of Guideline 指南目的This guideline describes the suggested contents for the 3.2.P.2 (Pharmaceutical Development) section of a regulatory submission in the ICH M4 Common Technical Document (CTD) format. 本指南就 CTD 格式申请文件中第3.2.P.2 章：药物开发需要叙述的内容给出了建议。
developmental biology 英文原版书
developmental biology 英文原版书Developmental biology is the study of the process by which organisms grow and develop. It examines how cells differentiate into specialized cell types, how tissues form organs, and how organisms develop from a single fertilized egg into complex multicellular organisms. Understanding developmental biology is crucial for various fields, including medicine, agriculture, and evolutionary biology.One of the foundational textbooks in the field of developmental biology is "Developmental Biology" by Scott F. Gilbert. First published in 1985, the textbook has since become a staple in undergraduate and graduate courses in developmental biology. The book covers a wide range of topics, including embryonic development, morphogenesis, and evolutionary developmental biology (or "evo-devo").One of the key strengths of Gilbert's "Developmental Biology" is its comprehensive coverage of the field. The textbook provides a detailed exploration of the molecular, cellular, and genetic mechanisms that underlie development. It also delves into the environmental factors that influence development, such as nutrition, stress, and epigenetics. By integrating thesedifferent levels of analysis, the book offers a holistic understanding of the complex processes of development.Another feature of "Developmental Biology" is its emphasis on experimental approaches. The textbook includes numerous examples of classic experiments that have shaped our understanding of developmental biology. From early studies on embryonic induction to more recent research on stem cells and tissue regeneration, Gilbert highlights the importance of experimental evidence in advancing our knowledge of development.In addition to its thorough coverage of developmental biology concepts, Gilbert's textbook also explores the broader implications of developmental biology for other disciplines. The book discusses how insights from developmental biology can inform medical research, conservation efforts, and our understanding of evolution. By highlighting the interconnectedness of different fields, Gilbert underscores the relevance of developmental biology across diverse areas of study.Overall, "Developmental Biology" by Scott F. Gilbert is a valuable resource for anyone interested in understanding the intricate processes of organismal development. Whether you area student, a researcher, or a science enthusiast, this textbook offers a comprehensive overview of the field of developmental biology. Its clear writing style, engaging illustrations, and deep insights make it a must-read for anyone curious about how organisms grow and evolve.。
举例说明战略计划的重要性
举例说明战略计划的重要性英文回答：The importance of strategic planning cannot be overstated. It is a critical process that helps organizations set their direction, make informed decisions, and achieve their goals. Strategic planning provides a roadmap for success and ensures that everyone in the organization is aligned towards a common vision.One example of the importance of strategic planning is the success story of Apple Inc. In the late 1990s, Apple was struggling and on the verge of bankruptcy. However, under the leadership of Steve Jobs, the company underwent a strategic transformation. Jobs implemented a clear vision and strategy, focusing on innovation and design. This strategic shift led to the development of iconic products like the iPod, iPhone, and iPad, which revolutionized the technology industry and propelled Apple to become one of the most valuable companies in the world.Another example is the strategic planning undertaken by Starbucks. In the early 2000s, Starbucks faced intense competition and declining sales. The company realized the need to reposition itself and embarked on a strategic planto regain its market share. Starbucks introduced new products, expanded its global presence, and focused on enhancing the customer experience. These strategicinitiatives helped Starbucks regain its momentum and become one of the most recognized and successful coffee chains worldwide.Strategic planning is not limited to large corporations. Small businesses can also benefit greatly from having awell-defined strategy. For instance, a local bakery mayface challenges from competitors and changing consumer preferences. By undertaking strategic planning, the bakery can identify its unique selling proposition, targetspecific customer segments, and develop a plan to differentiate itself. This strategic approach can help the bakery attract more customers, increase sales, andultimately thrive in a competitive market.In conclusion, strategic planning is crucial for organizations of all sizes and industries. It provides a roadmap for success, helps organizations adapt to changing market conditions, and ensures that everyone is working towards a common goal. The examples of Apple, Starbucks, and a local bakery illustrate the transformative power of strategic planning in achieving business objectives.中文回答：战略计划的重要性不可低估。
Unit 6 Market Development Strategies
Direct selling: an immediate channel to the marketplace that offers customers a good service.
b. Market development strategies （市场开发战略）
• Strategies to grow by selling existing products to new customers. • Companies seeking global markets for their products are using this strategy.
• Portfolio matrix（组合矩阵）
(1). Problem children: question mark
• show rapid growth but poor profit margins • have a low market share in a high-growth industry • Need a great deal of cash • Without cash support, they eventually become dogs. • Strategies: invest heavily to gain better market shares
4. Organizational strategies（企业战略）
(1). Intensive development strategies （密集型发展战略） a. Market penetration strategies（市场 渗透战略）: strategies to grow by selling more of the organization’s existing products to its existing customers or new customers.
管理学书籍
Service Management, 3rd服务管理，第三版作者：James A.Fitzsimmons （University of Texas-Austin）ISBN：0071181156出版年代：2001出版社：McGraw-Hill目录原价(USD)：19.95 人民币零售价：135.00教辅材料：教师手册内容简介：Service Management is the best-selling text in this market and includes fantastic and current examples from the field of technology. The text has extensive coverage on global operations, and the need for continuous improvement in quality and productivity in the service industy. Service Management also does an excellent job of demonstrating how crucial functional areas of organization such as marketing, strategic issues, operations and human behavior impact effective service management.本书是该领域的畅销书，其突出特点为包含技术领域精彩而适时的例证。
该书内容涉及全球运营、服务业质量与产量持续改进的需求等。
主要章节：Part I Understanding Services1. The Role of Services and the Economy2. The Nature of Services3. Service Quality4. Service StrategyPart II Designing the Service Enterprise5. New Service Development and ProcessDesign6. The Supporting Facility7. Service Facility Location8. The Service Encounter8S. Chapter Supplement: Work Measurement9. Internet ServicePart III Managing Service Operations10. Forecasting Demand for Services11. Managing Waiting Lines11S. Chapter Supplement: Computer Simulation12. Capacity Planning13. Managing Capacity and Demand14. Managing Facilitating Goods15. Service and Supply Chain Management 15S. Chapter Supplement: Vehicle Routing16. Managing Service Projects17. Linear Programming Applications inServicesPart IV Toward World-Class Service18. Quality and Productivity Improvement 18S. Chapter Supplement: Data Envelopment Analysis (DEA)19. Growth and Global Expansion Appendix A: Areas of a Standard Normal DistributionAppendix B: Uniformly Distributed Random Numbers [0,1]Appendix C: Values for Lq for the M/M/c Queuing ModelAppendix D: Equations for SelectedQueuing ModelsProject Management项目管理作者：Clifford F.Gray （Oregon State University）ISBN：0071163166出版年代：2000 页数：496出版社：McGraw-Hill目录原价(USD)：22.95 人民币零售价：175.00教辅材料：教师手册（题库）/教师光盘内容简介：Project Management is a text with cases; it is suitable for a course in project management and for professionals who seek a project management handbook. This text addresses the major questions and issues the authors have encountered while teaching and consulting with practicing project managers in domestic and foreign countries. The text is very contemporary and up-to-date. This application-oriented text provides a road map for managing any type of project--for example, information technology, R & D, engineering design, construction, pharmaceutical, and manufacturing. The text helps the reader discover the strategic role of projects in contemporary organizations, how projects are prioritized, what tools and techniques can be used to plan and schedule projects, what organization and managerial styles will improve chances of project success, how project managers orchestrate the complex network of relationships, factors that contribute to the development of a high performing project team, the project system which will help gain some measure of control, how project managers prepare for a new international project in a foreign culture, and finally how senior management can develop a supportive organizational culture for implementing projects. Gray and Larson present balanced view of the technical and socio/cultural dimensions of managing projects.本书包含教程与案例，既适宜于项目管理的课堂教学，又可作为业内人士的工作参考书。
关于海洋生物制药的潜力与挑战 英语作文
The Potential and Challenges of Marine BiopharmaceuticalsMarine biopharmaceuticals represent a promising frontier in the field of medicine.The vast and diverse marine environment is home to countless species,many of which produce unique bioactive compounds with potential therapeutic applications.However,despite the immense potential,there are significant challenges that must be addressed to fully harness the benefits of marine biopharmaceuticals.Potential of Marine BiopharmaceuticalsUnique Bioactive CompoundsMarine organisms,including sponges,corals,algae,and microorganisms, produce a wide array of bioactive compounds as part of their defense mechanisms or metabolic processes.These compounds often possess unique chemical structures not found in terrestrial organisms,making them valuable sources for new drugs.For example:Anticancer Agents:Compounds such as bryostatin,derived from marine bryozoans,and trabectedin,from sea squirts,have shown potent anticancer properties and are being investigated for their therapeutic potential.Antibiotics:Marine bacteria and fungi have been found to produce novel antibiotics,which are crucial in the fight against antibiotic-resistant bacteria.For instance,the marine bacterium Salinisporatropica produces salinosporamide A,a potent anticancer and antibiotic agent.Anti-inflammatory Compounds:Marine-derived compounds like pseudopterosins,isolated from the sea whip Pseudopterogorgia elisabethae,exhibit strong anti-inflammatory properties and are being explored for treating inflammatory diseases.Biodiversity and Chemical DiversityThe marine environment is characterized by immense biodiversity, which translates into a vast reservoir of chemical diversity.This diversity enhances the likelihood of discovering novel compounds with unique mechanisms of action,making marine biopharmaceuticals a rich source of new drugs.The exploration of deep-sea habitats,coral reefs,andhydrothermal vents continues to reveal new species and bioactive compounds with potential therapeutic applications.Sustainable Drug DevelopmentMarine biopharmaceuticals offer opportunities for sustainable drug development.Advances in biotechnology and synthetic biology enable the sustainable production of marine-derived compounds through microbial fermentation and chemical synthesis.This reduces the need for harvesting large quantities of marine organisms,thereby minimizing environmental impact and ensuring a stable supply of bioactive compounds.Challenges of Marine BiopharmaceuticalsDiscovery and IsolationThe discovery and isolation of bioactive compounds from marine organisms present significant challenges.Marine environments are often difficult to access,requiring specialized equipment and expertise. Additionally,the concentration of bioactive compounds in marine organisms is typically low,necessitating the collection of large quantities of specimens for extraction and analysis.This process is time-consuming and resource-intensive.Complex Chemical StructuresMarine-derived compounds often possess complex chemical structures, making them challenging to synthesize and modify for drug development.The complexity of these structures can hinder the optimization of pharmacokinetic properties and the large-scale production of these compounds.Advanced techniques in synthetic chemistry and biotechnology are required to overcome these challenges.Environmental and Ethical ConsiderationsThe harvesting of marine organisms for biopharmaceutical research raises environmental and ethical concerns.Overexploitation of marine resources can lead to habitat destruction and the depletion of species. Ensuring sustainable practices and adhering to ethical guidelines areessential to protect marine biodiversity and ecosystems.Conservation efforts and regulations must be in place to balance the benefits of marine biopharmaceuticals with the preservation of marine life.Regulatory and Commercialization HurdlesBringing marine-derived drugs to market involves navigating complex regulatory pathways and overcoming commercialization hurdles.The development of marine biopharmaceuticals requires extensive preclinical and clinical testing to ensure safety and efficacy.Additionally, the high costs associated with drug development,coupled with the uncertainty of market success,pose significant challenges for pharmaceutical companies.ConclusionMarine biopharmaceuticals hold immense potential for the development of new and effective drugs,offering solutions to some of the most pressing medical challenges.The unique bioactive compounds produced by marine organisms provide a rich source of novel therapeutics.However,realizing the full potential of marine biopharmaceuticals requires addressing the challenges of discovery, isolation,synthesis,and sustainable development.By overcoming these challenges,we can unlock the vast potential of the marine environment and contribute to the advancement of medicine and human health.。
生物利用度在药物发展过程中的意义英语作文
生物利用度在药物发展过程中的意义英语作文The significance of biological utilization in the drug development process lies in its ability to identify, understand, and leverage the natural resources and processes within living organisms to develop new drugs and therapies. By studying and harnessing the biological activities of various organisms, researchers can discover novel compounds, understand disease mechanisms, and develop new treatment modalities.Biological utilization involves the exploration of diverse natural sources such as plants, animals, and microorganisms for their potential therapeutic properties. For example, many traditional medicines have their origins in plant-based remedies, and modern drug discovery continues to draw inspiration from natural sources. By understanding the biological activities of these natural compounds, scientists can modify and optimize them to create more effective and safer drugs.In addition, biological utilization plays a crucial role in understanding disease processes and identifying potential drugtargets. By studying the biological pathways and molecular mechanisms involved in various diseases, researchers can identify key molecules and processes that can be targeted for therapeutic intervention. This knowledge is essential for developing new drugs that can effectively modulate disease processes and improve patient outcomes.Furthermore, biological utilization also encompasses the study of how drugs and therapies interact with living organisms. This includes understanding drug metabolism, pharmacokinetics, and drug interactions within the body. By studying these aspects, researchers can optimize drug dosing regimens, minimize side effects, and improve drug efficacy.Overall, biological utilization is essential in drug development as it provides a wealth of natural resources and insights that can lead to the discovery of new drugs, the understanding of disease processes, and the optimization of drug therapies. By harnessing the power of living organisms, researchers can continue to advance the field of drug development and improve patient care.生物利用度在药物发展过程中的意义在于其能够识别、理解和利用生物体内的自然资源和过程，以开发新药物和疗法。
New-ProductDevelopmentandProductLife-CycleStrategies解读
5
Stages of the New Product Development Process
Stage 2: Idea Screening
Product development costs increase substantially in later stages so poor ideas must be dropped Ideas are evaluated against criteria; most are eliminated
product idea product concept Product image
7
Stages of the New Product Development Process
Stage 4: Marketing Strategy Development
The target market, product positioning, and sales, share, and profit goals for the first few years. Product price, distribution, and marketing budget for the first year. Long-run sales and profit goals and the marketing mix strategy.
20
Product Life-Cycle Strategies
PLC Stages
Product development Introduction Growth Maturity Decline
Declining sales Low cost per customer Declining profits Laggards are targeted Declining competition
生物药 细胞培养 未来工作规划
生物药细胞培养未来工作规划英文回答：Biopharma Cell Culture Career Path.A career in biopharma cell culture offers a wide range of opportunities for professionals with a background inlife sciences. From research and development to manufacturing and operations, there are numerous roles that contribute to the development and production of therapeutic proteins and other biologics.Research and Development.Cell Culture Scientist: Responsible for developing and optimizing cell culture processes for the production of biologics. May specialize in areas such as cell line development, media optimization, and scale-up.Bioprocess Engineer: Designs and develops bioreactorsand other equipment used in cell culture production. Optimizes processes to improve efficiency, productivity, and quality.Analytical Scientist: Conducts assays and tests to ensure the quality and safety of biopharmaceuticals. May specialize in areas such as cell viability, product characterization, and impurity analysis.Manufacturing and Operations.Production Supervisor: Manages and oversees cell culture operations in a manufacturing facility. Ensures compliance with regulatory standards and quality control protocols.Cell Culture Operator: Operates and maintains bioreactors and other equipment used in cell culture production. Monitors cell growth and viability, and performs routine maintenance tasks.Quality Control Analyst: Conducts testing andinspections to ensure the quality of biopharmaceuticals. May specialize in areas such as product release testing and environmental monitoring.Other Career Paths.Regulatory Affairs: Ensures compliance with regulatory requirements for the development and production of biopharmaceuticals. Interacts with regulatory agencies and prepares documentation for product approvals.Business Development: Identifies and develops new business opportunities for biopharma companies. May negotiate contracts and manage relationships with clients and partners.Sales and Marketing: Promotes and sells biopharmaceuticals to healthcare professionals and other customers. Provides technical support and educates customers on product benefits.Career Progression.Career progression in biopharma cell culture typically follows a hierarchical structure, with opportunities for advancement based on experience, education, and performance. Junior scientists may start as Cell Culture Operators or Analytical Scientists and progress to more senior rolessuch as Production Supervisor or Bioprocess Engineer. With additional experience and qualifications, professionals may move into management positions such as Plant Manager or Director of Manufacturing.中文回答：生物制药细胞培养职业规划。
专家解说 生物多样性保护战略与行动计划
英文回答：Biodiversity conservation is one of the most important political issues on the planet and requires the development of scientifically sound conservation strategies and action plans. We should fully mobilize society as a whole to contribute our wisdom and strength to biodiversity conservation. In developing conservation strategies, we should start with conservation of priority areas, conservation of priority species and protection of ecosystem functions. In terms of action plans, specific protection measures, implementation schedules, monitoringand evaluation elements need to be identified. Only scientific conservation strategies and action plans can better address the challenges of biodiversity loss. The Government will actively guide and support relevant sectors and social forces in the implementation of policies and routes for biodiversity conservation to ensure the effective conservation and sustainable development of biodiversity.生物多样性保护是当前全球重要的议题之一，需要制定科学合理的保护战略与行动计划。
捕食螨天敌昆虫产品开发策略
捕食螨天敌昆虫产品开发策略英文回答：Developing a strategy for the production of predatory mite insect products requires careful planning and consideration. Here are some steps that can be taken to develop an effective strategy:1. Market Research: The first step is to conduct thorough market research to identify the demand for predatory mite insect products. This involves analyzing the target market, understanding customer needs and preferences, and identifying potential competitors. For example, I can conduct surveys or interviews with potential customers to gather insights into their requirements.2. Product Development: Once the market research is complete, it is important to focus on product development. This involves identifying the specific species of predatory mites that are most effective in controlling pests, anddeveloping a product line that includes these species. For instance, I can collaborate with entomologists and researchers to identify the most efficient predatory mite species for different types of pests.3. Production and Quality Control: After identifying the species of predatory mites, the next step is to establish a production process. This involves setting up breeding facilities, ensuring optimal conditions for mite reproduction, and implementing quality control measures to ensure the production of healthy and effective mites. For example, I can establish a breeding facility withcontrolled temperature and humidity to ensure the optimal growth of predatory mites.4. Packaging and Marketing: Packaging plays a crucial role in attracting customers and conveying the effectiveness of the product. It is important to design attractive and informative packaging that highlights the benefits of using predatory mite insect products. Additionally, effective marketing strategies, such as online advertising, trade shows, and partnerships with pestcontrol companies, can help reach a wider audience. For instance, I can collaborate with graphic designers to create visually appealing packaging that clearly communicates the advantages of using predatory mite insect products.5. Distribution and Sales: Developing a distribution network is essential to ensure that the products reach the target market effectively. This involves identifying potential distributors, establishing partnerships, and implementing efficient logistics systems. For example, I can partner with agricultural supply stores, online marketplaces, and pest control professionals to ensure widespread availability of the products.中文回答：制定捕食螨天敌昆虫产品的开发策略需要认真的规划和考虑。
加快药食同源产业发展的建议
加快药食同源产业发展的建议英文版Suggestions to Accelerate the Development of the Medicinal and Edible Homologous IndustryThe medicinal and edible homologous industry, also known as "Yao Shi Tong Yuan," refers to the integration of traditional Chinese medicine and food culture, promoting the development and utilization of both medicinal and edible plants. This industry holds immense potential for growth and innovation, yet its full potential remains untapped. To accelerate its progress, several key suggestions are offered.Strengthen Research and Development: Funding should be allocated to research institutions to conduct thorough studies on the pharmacological and nutritional properties of medicinal and edible plants. This will lead to the discovery of new compounds and the development of more effective products.Promote Education and Training: Educational institutions should offer specialized courses on medicinal and edible plants, fostering a new generation of experts in this field. This will ensure a continuous supply of skilled manpower to support the industry's growth.Regulate and Standardize: Strict quality control measures and standardization procedures should be implemented to ensure the safety and efficacy of products. This will boost consumer confidence and expand the market.Encourage Innovation and Collaboration: Encourage companies and research institutions to collaborate and innovate, leveraging technology to enhance production efficiency and product quality. This will foster a competitive yet collaborative environment, driving the industry forward.Expand International Markets: Explore opportunities for exporting medicinal and edible products to international markets, especially those with a growing interest in natural andhealthy products. This will expand the industry's reach and revenue.In conclusion, the medicinal and edible homologous industry offers significant opportunities for growth and innovation. By strengthening research, promoting education, regulating standards, encouraging innovation, and expanding international markets, we can accelerate its progress and unlock its full potential.中文版加快药食同源产业发展的建议药食同源产业，即“药食同源”，指的是将传统中医药与食品文化相结合，促进药用和食用植物的开发利用。
济宁2024年02版小学六年级上册第10次英语第五单元真题试卷
济宁2024年02版小学六年级上册英语第五单元真题试卷考试时间:60分钟（总分:140）考试人：_________题号一二三总分得分一、(选择题)总分:45分(1分/题)1、Which of these is a popular dessert?A) SaladB) CakeC) SoupD) Rice2、How many fingers do humans have on one hand?A) FourB) FiveC) SixD) Seven3、What is the color of a snowflake?中文解释：雪花是什么颜色的？A) WhiteB) BlueC) Gray4、What is the English word for "海星"?A) Sea cucumberB) StarfishC) JellyfishD) Coral5、What does "植物产业发展战略" mean in English?A) Plant industry development strategyB) Agricultural strategyC) Environmental strategyD) Ecological strategy6、Which one is a common breakfast food?A) PizzaB) CerealC) HamburgerD) Spaghetti7、What is a common vegetable used in salads?A) PotatoB) LettuceC) CornD) Pumpkin8、What type of plant grows back every year?中文解释：哪种植物每年都会重新生长？A. AnnualB. PerennialC. Biennial9、跟读下列对话。
1. -I'd like some bread, please-Here you are2. -Can I have some milk?-Here you are.-Thanks-You're welcome.10、What is the main ingredient in pancakes?中文解释：煎饼的主要成分是什么？A) FlourB) EggsC) Sugar11、Which fruit is red and round?A) BananaB) CherryC) GrapeD) Lemon12、What do we call a plant that grows in a garden?中文解释：我们称生长在花园中的植物为？A. Ornamental plantB. Wild plantC. Weeds13、读短文，选词填空。
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Imaging modalities for cancer screening and early detection
Human samples
♦ plasma/serum ♦ tissues
Cancer Signatures in the blood
Early detection Signatures
Blood collected Up to 2 years prior to Dx
Blood collected at Dx
Increasing Risk
<30 pack-year smoking history (Ever smokers not Currently elighible For screening)
Never smokers
Total deaths from lung cancer in the US in 2015: 160,000 If all high risk subjects were screened mortality would only be reduced by 8,000
Targeted sites:
• Breast: Mammography • Colon: Colonoscopy • Lung: LDCT
Issues:
• Limited sensitivity and specificity • Cost • Exposure to radiation and other adverse effects
Which is cancer?
Solution
30 pack-year smoking history, currently CT + smoke or quit within the past 15 years Blood Test
Increasing Risk
Blood test followed by CT
Major Requirement for Discovery Technology
In depth quantitative analysis
Proteomics using Ion Mobility Mass Spectrometry
• Includes an additional orthogonal dimension of separation without increasing analysis time • Improves the confidence in measurement of mono-isotopic accurate mass for both peptide and its fragment ions
• • • • •
Women’s Health Initiative Physician’s Health Study CARET Cohort EPIC PLCO
From the tumor….to ….. blood
- Nucleic acids: - Mutated DNA - Methylated DNA - Non-coding RNA - Proteins - Metabolites - Circulating tumor cells - Circulating tumor particles/ exosomes - Immune related: - Cytokines/chemokines - Autoantibodies
• Opportunity to reduce lung cancer mortality through blood screening. • Currently CT screening is only recommended for highest risk smokers • Uptake of CT screening worldwide has been very limited because of cost and complications • Opportunity to apply a blood test to screen all smokers not just highest risk
The US Preventive Services Task Force recommends low-dose CT annually only for high risk adults
30 pack-year smoking history, currently smoke or quit within the past 15 years are eligible for Low dose CT screening LDCT and represent a minority of lung ca
(most impactful for mortality reduction)
<30 pack-year smoking history (Ever smokers)
Never smokers
Total deaths from lung cancer in the US in 2015: 160,000
O60603 | Toll-like receptor 2 (TLR2)
MPHTLWMVWVLGVIISLSKEESSNQASLSCDRNGICKGSSGSLNSIPSGLTEAVKSLDLSNNRIT YISNSDLQRCVNLQALVLTSNGINTIEEDSFSSLGSLEHLDLSYNYLSNLSSSWFKPLSSLTFLNLL GNPYKTLGETSLFSHLTKLQILRVGNMDTFTKIQRKDFAGLTFLEELEIDASDLQSYEPKSLKSIQ NVSHLILHMKQHILLLEIFVDVTSSVECLELRDTDLDTFHFSELSTGETNSLIKKFTFRNVK ITDESL FQVMKLLNQISGLLELEFDDCTLNGVGNFRASDNDRVIDPGKVETLTIRRLHIPRFYLFYDLSTLY SLTERVKRITVENSKVFLVPCLLSQHLKSLEYLDLSENLMVEEYLKNSACEDAWPSLQTLILRQN HLASLEKTGETLLTLKNLTNIDISKNSFHSMPETCQWPEKMKYLNLSSTRIHSVTGCIPKTLEILDV SNNNLNLFSLNLPQLKELYISRNKLMTLPDASLLPMLLVLKISRNAITTFSKEQLDSFHTLKTLEAG GNNFICSCEFLSFTQEQQALAKVLIDWPANYLCDSPSHVRGQQVQDVRLSVSECHRTALVSGM CCALFLLILLTGVLCHRFHGLWYMKMMWAWLQAKRKPRKAPSRNICYDAFVSYSERDAYWVE NLMVQELENFNPPFKLCLHKRDFIPGKWIIDNIIDSIEKSHKTVFVLSENFVKSEWCKYELDFSHFR LFDENNDAAILILLEPIEKKAIPQRFCKLRKIMNTKTYLEWPMDEAQREGFWVNLRAAIK MPHTLWMVWVLGVIISLSKEESSNQASLSCDRNGICKGSSGSLNSIPSGLTEAVKSLDLSNNRIT YISNSDLQRCVNLQALVLTSNGINTIEEDSFSSLGSLEHLDLSYNYLSNLSSSWFKPLSSLTFLNLL GNPYKTLGETSLFSHLTKLQILRVGNMDTFTKIQRKDFAGLTFLEELEIDASDLQSYEPKSLKSIQ NVSHLILHMKQHILLLEIFVDVTSSVECLELRDTDLDTFHFSELSTGETNSLIKKFTFRNVK ITDESL FQVMKLLNQISGLLELEFDDCTLNGVGNFRASDNDRVIDPGKVETLTIRRLHIPRFYLFYDLSTLY SLTERVKRITVENSKVFLVPCLLSQHLKSLEYLDLSENLMVEEYLKNSACEDAWPSLQTLILRQN HLASLEKTGETLLTLKNLTNIDISKNSFHSMPETCQWPEKMKYLNLSSTRIHSVTGCIPKTLEILDV SNNNLNLFSLNLPQLKELYISRNKLMTLPDASLLPMLLVLKISRNAITTFSKEQLDSFHTLKTLEAG GNNFICSCEFLSFTQEQQALAKVLIDWPANYLCDSPSHVRGQQVQDVRLSVSECHRTALVSGM CCALFLLILLTGVLCHRFHGLWYMKMMWAWLQAKRKPRKAPSRNICYDAFVSYSERDAYWVE NLMVQELENFNPPFKLCLHKRDFIPGKWIIDNIIDSIEKSHKTVFVLSENFVKSEWCKYELDFSHFR LFDENNDAAILILLEPIEKKAIPQRFCKLRKIMNTKTYLEWPMDEAQREGFWVNLRAAIK MPHTLWMVWVLGVIISLSKEESSNQASLSCDRNGICKGSSGSLNSIPSGLTEAVKSLDLSNNRIT YISNSDLQRCVNLQALVLTSNGINTIEEDSFSSLGSLEHLDLSYNYLSNLSSSWFKPLSSLTFLNLL GNPYKTLGETSLFSHLTKLQILRVGNMDTFTKIQRKDFAGLTFLEELEIDASDLQSYEPKSLKSIQ NVSHLILHMKQHILLLEIFVDVTSSVECLELRDTDLDTFHFSELSTGETNSLIKKFTFRNVK ITDESL FQVMKLLNQISGLLELEFDDCTLNGVGNFRASDNDRVIDPGKVETLTIRRLHIPRFYLFYDLSTLY SLTERVKRITVENSKVFLVPCLLSQHLKSLEYLDLSENLMVEEYLKNSACEDAWPSLQTLILRQN HLASLEKTGETLLTLKNLTNIDISKNSFHSMPETCQWPEKMKYLNLSSTRIHSVTGCIPKTLEILDV SNNNLNLFSLNLPQLKELYISRNKLMTLPDASLLPMLLVLKISRNAITTFSKEQLDSFHTLKTLEAG GNNFICSCEFLSFTQEQQALAKVLIDWPANYLCDSPSHVRGQQVQDVRLSVSECHRTALVSGM CCALFLLILLTGVLCHRFHGLWYMKMMWAWLQAKRKPRKAPSRNICYDAFVSYSERDAYWVE NLMVQELENFNPPFKLCLHKRDFIPGKWIIDNIIDSIEKSHKTVFVLSENFVKSEWCKYELDFSHFR LFDENNDAAILILLEPIEKKAIPQRFCKLRKIMNTKTYLEWPMDEAQREGFWVNLRAAIK MPHTLWMVWVLGVIISLSKEESSNQASLSCDRNGICKGSSGSLNSIPSGLTEAVKSLDLSNNRIT YISNSDLQRCVNLQALVLTSNGINTIEEDSFSSLGSLEHLDLSYNYLSNLSSSWFKPLSSLTFLNLL GNPYKTLGETSLFSHLTKLQILRVGNMDTFTKIQRKDFAGLTFLEELEIDASDLQSYEPKSLKSIQ NVSHLILHMKQHILLLEIFVDVTSSVECLELRDTDLDTFHFSELSTGETNSLIKKFTFRNVKITDESL FQVMKLLNQISGLLELEFDDCTLNGVGNFRASDNDRVIDPGKVETLTIRRLHIPRFYLFYDLSTLY SLTERVKRITVENSKVFLVPCLLSQHLKSLEYLDLSENLMVEEYLKNSACEDAWPSLQTLILRQN HLASLEKTGETLLTLKNLTNIDISKNSFHSMPETCQWPEKMKYLNLSSTRIHSVTGCIPKTLEILDV SNNNLNLFSLNLPQLKELYISRNKLMTLPDASLLPMLLVLKISRNAITTFSKEQLDSFHTLKTLEAG GNNFICSCEFLSFTQEQQALAKVLIDWPANYLCDSPSHVRGQQVQDVRLSVSECHRTALVSGM CCALFLLILLTGVLCHRFHGLWYMKMMWAWLQAKRKPRKAPSRNICYDAFVSYSERDAYWVE NLMVQELENFNPPFKLCLHKRDFIPGKWIIDNIIDSIEKSHKTVFVLSENFVKSEWCKYELDFSHFR LFDENNDAAILILLEPIEKKAIPQRFCKLRKIMNTKTYLEWPMDEAQREGFWVNLRAAIK