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boullee essay ÉTIENNE-LOUIS BOULLÉ, Newton’s Cenotaph, 1780-93. Francisco Martínez Mindeguía, Universitat Politècnica de Catalunya. Étienne-Louis Boullée, Newton’s Cenotaph, 1780-93. Paper Check. This is the façade of Newton's cenotaph, possibly Boullée’s most emblematic project. A project that allows us to understand what he meant by saying that the architect should aim at the sublime. A concept that we should not relate exclusively to the greatness . Étienne-Louis Boullée (1728-1799) wanted to be a painter and ended up studying architecture at essay Jacques-François Blondel’s school, owing to parental pressure. At the paper off, age of 19 he became a teacher at the École des Ponts et Chausées, at 34 was admitted as a second class member at the Académie d'Architecture and at 52 as a first class member, until the National Convention abolished the Academy in 1793. He was one of the founders of the Institut National des Sciences et des Arts in 1795.

At 52 he began writing Architecture, Essai sur l'art , which he finished between 1790 and 1793, although it was not published until 1953. His book is writing a critical essay illustrated with drawings of paper off, projects for public buildings he designed between 1778 and 1788: churches, palaces, courts, assemblies, theaters, libraries, museums, city gates, memorial arches, bridges, lighthouses, cemeteries, cenotaphsAfter his death, his figure was forgotten, hidden behind the published work of Ledoux and writing executives, Durand; he was despised by the classics, who saw him as an eccentric seeking to paper off overthrow traditions, and by the moderns who made him responsible for the neoclassical deviations towards historicism and writing essay short, plagiarism. His book contains the key to the understanding of architecture drawing, namely Newton's cenotaph. Blondel said that the building is to find greatness. He particularly said: I tried to apply all the models the nature and art offered me in order to present the image of the great (Architecture. Essay on art. Off. GG, pg. 70). Then follows: The picture of the great has such sway over our senses that, even if we consider it horrible, it always provokes us a feeling of admiration.

A volcano spewing lava and death is writing story a terribly beautiful image! . Greatness is directly related to beauty and, under different meanings, it is the same whether objects are pleasant or horrifying. Looking grand in paper check, anything means revealing superior qualities (Essay, p. 76). It is an a critical on a argument that matches the concept of the paper off, sublime expounded by Edmund Burke. He also said: the image of greatness satisfies us in every aspect because our soul, eager to extend its joys, seems ready to embrace the Universe ( Essay . p. 59). Besides from large size, the sublime is achieved by simple forms. He said : Why does the regular shaped figure emphasized at first sight?

Because its faces are regular and recurrent and because its form is simple. We distinguish them thanks to the image of order that their regularity and symmetry suggest. Argumentative Essay On Declaration Of Independence. The regularity sets the beauty of form; symmetry, order, and overall beauty; variety produces various levels by means of which they are diversified to us . Paper Check Off. Proportion is an effect that arises from regularity, symmetry and varietyThe harmony of the bodies is born from the combination and the perfect conjunction of all its proportions (Essay. p. With Assignments. 56). Such assessments are those that justify this building’s form. Basically, the building is check a large sphere that represents both the writing on a short, land and Newton’s discoveries. Paper Off. Its access can be gained through the base and, despite its size, only a small area of such base can be occupied. Its surface is skilfully perforated, so that sunlight can enter during the day and create the picture of the night sky. At night a great source of artificial light in the centre portrays the daytime image . Light represents Newton, lighting the knowledge of service executives, mankind. From the paper off, outside, one can only see half the sphere, supported by two cylinders. Around this sphere, along its perimeter, Boullée places rows of trees. This image recalls Roman tradition in the great mausoleums of Augustus and Hadrian, even though they are different building types, since a mausoleum is a grave and a cenotaph is a monument dedicated to the memory of someone, but inside which no body is preserved.

Boullée’s idea coincides with the epitaph written by Alexander Pope in 1732: Nature and the laws of nature were hidden at night. God said, “Let Newton be born!” and essay on declaration, all was light. Following the text of his Essai sur l'art : “To produce sad and dark images it is necessary to present architecture by paper off means of a completely bare wall, as I intendedin some funerary buildings, showing a picture of sunken architecture by means of assignments uk, low proportions and paper check off, buried into the ground; in short, give shape, by means of light absorbing materials, to the dark image of an architecture defined by the shadow effect. This type of shadow-in tegrated architecture is an artistic discovery that belongs to me . (Essay , p.71) Boullée and writing service, the architecture of paper check, shadows . For Boullée, however, this shadow is inseparable from light. 10 Best Resume Service Executives. In other words, it is a shadow the purpose of which is the sublime perception of light. It is check off not for a light that shines, but for one that could dazzle, overtake and paralyze. And he applies this concept in invisible resume, public places: museums, libraries, theaters, churches, palaces. One of such buildings is the basilica. Boullée describes it as the paper check off, basilica or metropolitan church of Corpus Christi Day, as he says : a house of holiness inhabited by the most worthy ministers of religion. The scenic effect is obvious in the interior perspective drawing: the light on the altar, around the cross, the priest in ecstasy, the faithful ascending the writing essay short story, stairs and kneeling in the contemplation of the miracle of the Eucharist. Boullée describes it as the basilica or metropolitan church of Corpus Christi Day, as he says : a house of holiness inhabited by the worthiest ministers of religion.

The scenic effect is paper obvious in the interior perspective drawing: the light at the altar, around the cross, the priest in ecstasy, the faithful ascending the stairs and kneeling in contemplation of the miracle of the Eucharist. Some drawings show a sublime experience. As he says, the objective is to arouse in us a deep worship: this is the writing a critical essay, goal of paper check off, religious ceremonies. It is therefore necessary to how to write report example use all appropriate means to give a character of grandeur and majesty (Essay, p. 62) . This place . would also make our soul experience a feeling of joy and would be our truly earthly paradise (Essay, p. 64) . . here's what would make this event not only something august/magnificent and off, exciting, but also truly celestial (Essay, p.64) Boullée begins his book by asking “what is writing essay architecture?” and denies that it is the art of building , to quote Vitruvius. Architecture is a product of the mind, the paper check, fruit of spiritual and intellectual activity and precedes construction. He clarifies that the art of architecture is different from the construction technique. Art is generated by a creative inspiration, while technique is only a mechanical process.

He thus confronts the vitruvian approach. But Boullée goes farther: the a critical essay short, first issue in architecture is neither technical nor aesthetic, but philosophical and ethical. Origin of the images: All the images are from Étienne-Louis Boullée, Arquitectura, ensayo sobre el arte , Barcelona, Gustavo Gili, 1985. - Étienne-Louis Boullée, Architecture, Essai sur l'art , 1793. The quoted translations correspond to paper check the Gustavo Gili Spanish Editing. - Emil Kaufmann, Étienne-Louis Boullée, The Art Bulletin , vol. 21, nº 3, 1939, pp. 213-227. - Emil Kaufmann, Tres arquitectos revolucionarios: Boullée, Ledoux y Lequeu , 1952, 1978.

Francisco Martínez Mindeguía is Profesor Agregado at story the Superior Technical Architecture School of Vallès (Escuela Técnica Superior de Arquitectura del Vallès), UPC.

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IBM Security Access Manager / Tivoli Access Mgr. BALTIMORE , MD 21217. IBM Global Business Services (GBS) is a team of business, strategy and technology consultants enabling enterprises to make smarter decisions and providing unparalleled client and consumer experiences in cognitive, data analytics, cloud technology and mobile app development. With global reach, outcome-focused methodologies and deep industry expertise, IBM GBS empowers clients to digitally reinvent their business and paper check off, get the competitive edge in the cognitive era in over 170 countries.Bottom line? Support testing and debugging of configurations + Work is located in Woodlawn, MD The Public Service Sector consulting practice is a trusted advisor to federal, state and local governments, partnering to meet challenges and responding quickly to citizen demands, business needs, new economic conditions, and changing legislative priorities and policiesBENEFITS Health Insurance. Paid time off. https://www-03.ibm.com/press/us/en/pressrelease/50744.wss CAREER GROWTH Our goal is to be essential to the world, which starts with our people. Company wide we kicked off an internal talent strategy program called Go Organic. http://www.ibm.com/ibm/responsibility/corporateservicecorps PSHJ 1SCTY DCHJ GBSPSDC IBM Security Access Manager (formerly Tivoli Access Manager so either one) LDAP Web Security Global Services IBM is committed to creating a diverse environment and is proud to be an equal opportunity employer. All qualified applicants will receive consideration for employment without regard to race, color, religion, gender, gender identity or expression, sexual orientation, national origin, genetics, disability, age, or veteran status. IBM is also committed to compliance with all fair employment practices regarding citizenship and immigration status.

Create a job alert for essay, IBM Security Access Manager / Tivoli Access Mgr at BALTIMORE, MD. Great! You'll now receive job alerts for off, IBM Security Access Manager / Tivoli Access Mgr at BALTIMORE, MD. Create a job alert for invisible resume, IBM Security Access Manager / Tivoli Access Mgr at BALTIMORE, MD. IBM Security Access Manager / Tivoli Access Mgr. Posted 1 days ago. VIEW JOBS 10/3/2017 12:00:00 AM 2018-01-01T00:00 IBM Global Business Services (GBS) is paper check off, a team of business, strategy and technology consultants enabling enterprises to make smarter decisions and providing unparalleled client and argumentative on declaration of independence, consumer experiences in cognitive, data analytics, cloud technology and mobile app development. With global reach, outcome-focused methodologies and deep industry expertise, IBM GBS empowers clients to digitally reinvent their business and get the competitive edge in the cognitive era in over 170 countries.Bottom line? We outthink ordinary. Check? Discover what you can do at IBM.In this exciting role you will have a strong background with the IBM Security Access Manager product (formerly Tivoli Access Manager) to integrate on prem and cloud applications into enterprise security frameworks.Job Duties include: + Research tools and information required to integrate ISAM(indexed sequential access method) with systems and applications + Work with development teams to help uk integrate ISAM with backend applications. + Support testing and debugging of paper check off, configurations + Work is located in Woodlawn, MD The Public Service Sector consulting practice is invisible resume, a trusted advisor to federal, state and check off, local governments, partnering to how to write a interview example meet challenges and responding quickly to citizen demands, business needs, new economic conditions, and changing legislative priorities and policiesBENEFITS Health Insurance. Off? Paid time off.

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Company wide we kicked off an internal talent strategy program called Go Organic. At our core, we are committed to with believing and investing in check our workforce through: + Skill development: helping our employees grow their foundational skills + Finding the dream job at IBM: navigating our company with the potential for many careers by channeling an employee’s strengths and career aspirations + Diversity of people: Diversity of thought driving collective innovation In 2015, Go Organic filled approximately 50% of invisible, our open positions with internal talent that were promoted into the role. CORPORATE CITIZENSHIPWith an employee population of 375,000 in paper over 170 countries, amazingly we connect, collaborate, and care. IBMers drive a corporate culture of shared responsibility. We love grand challenges and a interview report example, everyday improvements for check off, our company and for the world. We care about each other, our clients, and the communities we live, work, and on declaration, play in! + http://www.ibm.com/ibm/responsibility/initiatives.html + http://www.ibm.com/ibm/responsibility/corporateservicecorps PSHJ 1SCTY DCHJ GBSPSDC IBM Security Access Manager (formerly Tivoli Access Manager so either one) • LDAP • Web Security Global Services IBM is committed to creating a diverse environment and is proud to be an equal opportunity employer.

All qualified applicants will receive consideration for employment without regard to race, color, religion, gender, gender identity or expression, sexual orientation, national origin, genetics, disability, age, or veteran status. IBM is also committed to compliance with all fair employment practices regarding citizenship and immigration status. IBM BALTIMORE MD. Posted 1 days ago. VIEW JOBS 10/3/2017 12:00:00 AM 2018-01-01T00:00 h3Job Description/h3divpTwenty-three million older adults with hearing loss go untreated.

Traditional hearing care demands resources exceeding those of check, many older adults. Example? Access HEARS is a start-up non-profit organization that looks to fill this need with an off evidence-based, affordable and accessible model that transcends cost, mobility, and literacy barriers. We revolutionized the delivery of hearing care by condensing a 6-month long process with multiple physician visits into a 2-hour training session, thereby removing the barriers to care, and decreasing cost using affordable hearing technology. Our mission is to 10 best writing enhance communication for older adults through education, counseling and paper off, attainment of hearing technology./ppUnder the direction and guidance of the Executive Director, the Client Services Manager (CSM) is essay necessary, responsible for delivering Access HEARS services to older adults with hearing loss. The CSM must obtain and maintain active Access HEARS certification, including having successfully completed initial certification training before delivering services. Paper Check Off? The CSM will work in an independent manner with minimal direction and supervision while upholding the highest standard of professionalism with strategic partners and a interview report example, clients at off all times./ppnbsp;/ppstrongGeneral Responsibilities:/strong/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Prospect, develop and maintain relationships with decision makers from organizations interested in receiving services from Access HEARS/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Schedule and perform community lectures introducing the a interview, Access HEARS services to solicit interest/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Meet with clients to deliver Access HEARS services/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Maintain detailed record of inventory/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Collect payment for paper check, devices sold/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Maintain detailed records of client interactions/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Continue supporting clients as needed/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Enable adoption of assistive hearing technology to improve the lives of older adults/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Seek out additional opportunities to 10 best resume executives enhance communication and social engagement among clients and older adults/ppnbsp;/ppstrongQualifications:/strong/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; A Bachelorrsquo;s degree or work experience with older adults/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Strong understanding of paper check, how to obtain and apply marketing and performance metrics/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Outstanding project management and argumentative essay of independence, communication skills/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Experience working with older adults/ppnbsp;/ppstrongDesired Skills:/strong/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Enjoys working with older adults from diverse backgrounds and educational levels/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Motivational interviewing skills to empower clients and check, engender skill attainment/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; High emotional intelligence to market, deliver, and support service delivery around a common, yet stigmatized concern/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Performs all duties in essay evil an independent manner with minimal direction and supervision/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Driven and highly self-motivated/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Promotes a high degree of positive morale, including encouraging teamwork and communication/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Excellent verbal and written skills, with ability to read, write, and act on general business information/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Aptitude to interpret a variety of instructions furnished in written, oral, diagram, and schedule format/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Ability to write routine reports and correspondence in paper off an accurate, timely, and 10 best writing service, legible manner/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Ability to present information effectively in one-on-one and group situations/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Ability to engage clients with an emphasis on approachability, professionalism, and trustworthiness/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Excellent span class=long-wordorganizational/multi/span-tasking skills with acute attention to details/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Recognizes and performs duties which need to be performed, although not directly assigned/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Ability to calculate figures and apply concepts of basic mathematics/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Proficiency with Microsoft Office Suite (Word, Excel, Power Point, Outlook)/ppnbsp;/ppstrongWork Environment and paper off, Physical Demands:/strong/ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Extensive and regular periods of argumentative essay on declaration of independence, sitting, standing, bending, walking, seeing, talking, and listening./ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Occasional requirement to reach with hands and arms and to stoop, kneel, crouch, or crawl./ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Occasional requirement to lift and/or move up to 30 pounds./ppbull;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Ability to operate a motor vehicle and drive for distances of at least 100 miles./ppnbsp;/ppstrongSummary Statement:/strong/ppThis job description is not intended and should not be construed to paper check off be an exhaustive list of all responsibilities, skills, efforts, or working conditions associated with the on advertising is a, job; it is intended to reflect those principal job elements essential for recruitment and selection, for check off, making fair job evaluations, and for establishing performance standards. Writing Essay On A Short? The physical demands described are representative of paper check, those that must be met by an employee to successfully perform the essential functions of this job. Reasonable accommodations may be made to enable individuals with disabilities to perform the essential functions./ppnbsp;/p/divh3Company Description/h3divAccess HEARS is invisible, a start-up non-profit organization that looks to fill the need by older adults with hearing loss find options using an evidence-based, affordable and accessible model that transcends cost, mobility, and literacy barriers./div Access Hears Baltimore MD.

Posted 1 days ago. VIEW JOBS 10/3/2017 12:00:00 AM 2018-01-01T00:00 IBM Global Business Services (GBS) is a team of business, strategy and technology consultants enabling enterprises to make smarter decisions and providing unparalleled client and consumer experiences in cognitive, data analytics, cloud technology and mobile app development. With global reach, outcome-focused methodologies and deep industry expertise, IBM GBS empowers clients to digitally reinvent their business and get the competitive edge in paper off the cognitive era in on advertising is a over 170 countries.Bottom line? We outthink ordinary. Discover what you can do at IBM. Data is the paper check, world's natural resource for the next century. In IBM Public Sector, we use the latest advanced analytics technologies, tools, and techniques to 10 best resume executives extract insights from this data. We work collaboratively with our government and healthcare clients and apply these insights to make complex and strategic decisions for the public's benefit.

Whether you are just starting your career, or at the top of your game, if you are excited about applying predictive, prescriptive, mission, and social analytics to off solve difficult problems, IBM's Advanced Analytics Public Sector team is the argumentative essay, place for you.The Analytics Expert will work with the project and client teams to research and support the development of predictive models and other analytics relating to disability fraud. Check Off? Work is performed at the client site with access to the client's claims data warehouse. Argumentative Essay Of Independence? Work with SSA operations and investigative SMEs to identify ways to paper check measure and model fraud vulnerabilities and to evaluate model performance. Lead and manage a team of help with assignments uk, experienced modelers.BENEFITS Health Insurance. Paid time off. Paper Check Off? Corporate Holidays. Sick leave. Family planning. Resume Writing Service Executives? Financial Guidance. Competitive 401K. Training and Learning.

We continue to paper check off expand our benefits and programs, offering some of the best support, guidance and coverage for a diverse employee population. On A Short Story? + http://www-01.ibm.com/employment/us/benefits/ + https://www-03.ibm.com/press/us/en/pressrelease/50744.wss CAREER GROWTH Our goal is to be essential to the world, which starts with our people. Check Off? Company wide we kicked off an internal talent strategy program called Go Organic. Essay Evil? At our core, we are committed to believing and investing in our workforce through: + Skill development: helping our employees grow their foundational skills + Finding the dream job at IBM: navigating our company with the potential for many careers by channeling an employee’s strengths and career aspirations + Diversity of people: Diversity of thought driving collective innovation In 2015, Go Organic filled approximately 50% of our open positions with internal talent that were promoted into the role. CORPORATE CITIZENSHIPWith an paper check employee population of 375,000 in writing a critical essay short over 170 countries, amazingly we connect, collaborate, and care. IBMers drive a corporate culture of check, shared responsibility. We love grand challenges and everyday improvements for our company and for the world. We care about each other, our clients, and the communities we live, work, and play in! + http://www.ibm.com/ibm/responsibility/initiatives.html + http://www.ibm.com/ibm/responsibility/corporateservicecorps Selected candidates may not need to on advertising travel for all projects outside of their metro area. However, all candidates must be able and willing to travel based on check off assigned project demand. Travel requirements may vary but could be up to 100%. Candidates are not able to refuse project based on travel.

Stay connected by subscribing to resume the IBM jobs blog (blog.ibm.jobs) for paper off, career insights, news and latest job opportunities. IBM Global Business Services: Join a Leader. Consult with us. (2252) PSHJ To be an official applicant to IBM, you must submit a resume and online application. Resumes submitted remain active for writing essay story, six months. To all recruitment agencies: IBM only accepts resumes from agencies on our Approved Agency List. Please do not forward resumes to our applicant tracking system, IBM employees, or send to off any IBM company location. IBM is not responsible for resume, any fees related to unsolicited resumes. + Knowledge of analytical methods, statistics, SPSS programming skills, SQL queries, SAS programming skills, and large scale data manipulation. + Ability to design and develop predictive models, and to conduct sound descriptive statistical analysis. + 5+ years of experience with analytical report writing and paper, client presentation skills. + Experience in on a analytics project management. Paper Check Off? Global Services IBM is committed to creating a diverse environment and on a short story, is proud to be an off equal opportunity employer. All qualified applicants will receive consideration for writing a critical essay on a story, employment without regard to check off race, color, religion, gender, gender identity or expression, sexual orientation, national origin, genetics, disability, age, or veteran status.

IBM is also committed to essay on advertising is a compliance with all fair employment practices regarding citizenship and immigration status. IBM BALTIMORE MD. IBM Security Access Manager / Tivoli Access Mgr. 1. Resume Copy paste or upload your resume. 2. Cover Letter (Optional) 2. Check Off? Cover Letter (Optional) Attached Cover Letter. 2. How To Write A Interview? Cover Letter (Optional) Copy paste or upload your cover letter.

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Histoire des Alpes - Storia delle Alpi - Geschichte der Alpen (1998)/09. PRODUKTION, VERARBEITUNG UND VERTEILUNG. [ 107 ] PRODUKTION, VERARBEITUNG UND VERTEILUNG UBERLEGUNGEN ZUR BEDEUTUNG METALLISCHER ROHSTOFFE BEI DER AUSBILDUNG POLITISCHER SYSTEME IM SUDBAYERISCHEN ALPENVORLAND WAHREND DER BRONZEZEIT. Check Off. Production, transformation et distribution. 10 Best Executives. Reflexions sur la signification des matieres premieres metalliques dans la formation des systemes politiques dans les prealpes bavaroises pendant l'Age du bronze. Paper Check. Cette contribution s’interesse aux possibilites qu’offrent les trouvailles et les resultats des fouilles archeologiques en vue de tirer des enseignements sur les processus politiques en jeu dans la partie meridionale des Alpes bavaroises durant l’Age du bronze. La situation bavaroise y est comparee a celle des pays de l’est de l’Europe centrale et du sud-est de l’Europe, qui sont plus faciles a caracteriser du fait de leur proximite des civilisations hautement developpees de la Mediterranee orientale. Help With Uk. Il apparait une concordance etonnante aussi bien dans le developpement chronologique de l’occupation que dans le genre et le but des ouvrages de fortification. Paper Off. Contrairement aux pays du Danube, le sud de la Baviere dispose d’un ensemble de sources supplementaire: les objets funeraires.

L’article essaie de montrer les liens existant entre les fortifications d’altitude des prealpes, les places fortifiees a la lisiere des Alpes, les lieux de stockage des metaux et les riches tombes avec leurs temoignages de l’extraction et de la transformation des metaux. How To Report Example. Cette demarche a ete rendue possible grace a un projet de recherche, qui doit permettre de mieux connaitre les dimensions economique et politique de la distribution du metal durant l’Age du bronze dans les prealpes orientales. Paper Off. Der Forschungsstand in Suddeutschland [2] ist im Vergleich mit demjenigen des mittleren und unteren Donauraumes, unter dessen Einfluss die Kulturen der suddeutschen Bronzezeit uberwiegend stehen, [3] nicht befriedigend. Dort lassen sich immerhin die Grundzuge der historischen Entwicklung einigermassen exakt umreissen: Nach einer Phase der fruhbronzezeitlichen Belegung (2000-1600 v. Write A Interview Example. Chr.) ist ein zeitweiliges Aussetzen in paper der Besiedlung von Hohenplatzen zu beobachten, die in argumentative Nordungarn und Siebenburgen erst mit der Stufe Bronze D, also im 13. Paper Check. vorchristlichen Jahrhundert wieder aufgenommen wird. In Westungarn und der Slowakei scheint der Hiatus kurzer zu sein und endet bereits in essay short der Mittelbronzezeit um 1500 v. Chr. Check. Fur die Auswahl des Platzes sind ausser strategischen Erwagungen auch naturliche Verkehrswege, etwa am Zusammentreffen von Flusstalern massgeblich. In vielen Fallen sind zudem direkte Zusammenhange mit den Lagerstatten naturlicher Ressourcen auszumachen. Fur das sudbayerische Alpenvorland und die Schotterplatten, weite Ebenen, die nach dem Ruckzug der eiszeitlichen Gletscher entstanden, ist lediglich der Kenntnisstand uber offene dorfliche Siedlungen in den letzten Jahren enorm gewachsen. [4] Einer relativen Dichte fruhbronzezeitlicher Graberfelder, denen erst seit neuestem zeitgleiche Siedlungen zugeordnet werden konnen, [5] folgt ein Absinken sowohl der Siedlungs- wie auch der Grab- und Hortfunde wahrend der mittleren Bronzezeit, fur das bisher keine plausible Erklarung zur Verfugung steht, das aber kaum eine tatsachliche Siedlungsleere widerspiegeln durfte.

Mit der spaten Bronzezeit, also seit dem 13. vorchristlichen Jahrhundert tritt dann der Siedlungstyp des Gehoftes mit mehreren Gebauden wohl unterschiedlicher Funktion auf, der sich ohne grossere Anderungen bis in die keltische Eisenzeit des 5./4. Jahrhunderts v. Chr. fortsetzt. Als bevorzugte Topographie ist wie in with assignments den Dona ulandern die Lage am Rand von Mooren oder Flussauen belegt und auch die Verkehrsgunst spielt eine entscheidende Rolle. [6] Eine andere Situation begegnet bei spatbronzezeitlich belegten Hohen- [ 109 ] Siedlungen des Alpenvorlandes, die prinzipiell seit langem bekannt sind; da jedoch ihre herausragende topographische Lage bis in off die jungste Zeit reprasentative Bauten anzog, fehlen gemeinhin befriedigende Aufschlusse zur Art der Befestigung und Besiedlung oder zu Zweck und Charakter. Writing Essay On A Story. [7] Die Dauer der Belegung lasst sich zumeist nur grob umreissen. Immerhin lasst das ostliche Sudbayern mit Hohensiedlungen wie dem Freisinger Domberg [8] einheitliche Belegungsfolgen erkennen, die mit spater Fruhbronzezeit (17./16. Paper Check Off. Jahrhundert v. Invisible Resume. Chr.), spater Mittelbronzezeit und Spatbronzezeit (14.-10. Jahrhundert v. Check Off. Chr.) Parallelen mit den Anlagen des Donauraumes zeigen. Eine weitere Gruppe mittel- bis spatbronzezeitlich belegter, burgahnlicher Hohenorte, deren chronologische Entwicklung vergleichbar mit jener der grossen Hohensiedlungen des Voralpenlandes ist, kontrollierte die Ein- beziehungsweise Ausgange zu den Alpentalern mit ihren Erzlagerstatten und Passen. Invisible Resume. [9] Damit erscheint ein soziookonomischer Zusammenhang gegeben, in paper check dem die drei Siedlungstypen des Voralpenlandes, namlich offene dorfliche Siedlungen, grosse, teilweise befestigte Hohensiedlungen im Flachland und kleinere Hohenplatze am Alpenrand unterschiedliche Funktionen besassen. Writing Short. Wie sahen diese Funktionen aus und in welcher Beziehung standen sie zum wichtigsten Wirtschaftsgut der Bronzezeit, dem Kupfererz der Ostalpen? In den Landern des ostlichen Mitteleuropa und Sudosteuropa ermoglicht die grosse Anzahl von entsprechenden Funden eine statistisch nachprufbare lokale Affinitat von Metallhorten zu befestigten Hohensiedlungen. Check. Sowenig uber die Rolle befestigter und unbefestigter Hohensiedlungen im Gefuge spatbronzezeitlicher Gesellschaften bekannt ist, so sehr legen doch Platzwahl und Art der Fortifikation den Schluss nahe, dass sie zum einen dazu dienten, geschatzte Werte vor rauberischem oder kriegerischem Zugriff zu schutzen; die stereotype Lage an writing executives, verkehrstechnisch und strategisch wichtigen Punkten und die regelhaft wiederkehrende Sitte der Niederlegung von Bronzedepots auf oder in off der Nahe solcher Burgen belegt, dass eine zweite Aufgabe die Sicherung oder Kontrolle von Handel und Verkehr war. [10] Uber die Art der Macht, die von diesen Platzen ausging, ist allerdings ebensowenig Aufschluss zu erhalten wie uber die Rolle und Funktion der herrschenden Personen oder Gruppen. Fur die vergleichbare Entwicklung in help with uk Suddeutschland kann die Hohensiedlung «Rachelburg» uber den nordlichsten Randhohen des Alpeninn- [ 110 ] Abb.

1: Die Lage der spatbronzezeitlichen Hohensiedlung Rachelburg im Gefuge der Nordtiroler Urnenfelder (13.-10/9. Jahrhundert v. Chr.). Check Off. Dreieck: Hohensiedlung Rachelburg; Offene Quadrate: Urnenfelder im Bereich der Rachelburg; Gefullte Quadrate: Urnenfelder des Tiroler Inntales. [ 111 ] Abb. 2: Rohgusskuchen aus Fahlerzen des Tiroler Inntales. Invisible Resume. Hortfund vom Fuss der Hohensiedlung «Rachelburg», Gemeinde Flintsbach, Landkreis Rosenheim, Oberbayern. Abgebildet sind ganze Gusskuchen (links oben), Halb- bis Drittelfraktionen (rechts oben), Viertelfraktionen (links unten) und Reste des Schmelzvorganges (rechts unten). tales als idealtypisch gelten, [11] ein Ensemble, dessen einzelne Bestandteile, namlich Burg oder Akropolis, geschutzte Hohensiedlung und Talsiedlung ohne Zweifel in paper off einem Funktionszusammenhang standen (Abb. I). [12] Einen Schlussel zur Deutung stellt ein Hortfund dar, der 1992 im Bereich der Talsiedlung bei der Erweiterung einer Sandgrube entdeckt und planmassig geborgen werden konnte. With Uk. Es handelte sich dabei um Gusskuchen mit einem Gesamtgewicht von fast genau 50 kg, die in ein Gefass geschichtet waren. Sie wiesen unterschiedliche Grossen und Gewichte auf, wobei der uberwiegende Teil aus Bruchstucken mit identifizierbaren Fraktionen bis zu einem Viertel bestand (Abb. Paper Check Off. 2).

Die Datierung liegt zwischen Bz D und Ha A2 also im Zeitraum zwischen 1300 und 1000 v. Essay Of Independence. Chr. Check. Nun sind Brucherzhorte in 10 best service executives Suddeutschland zwar nicht gerade selten, [13] nur in Ausnahmefallen erreichen sie allerdings das Gewicht des Flintsbacher Depots und nie sind sie mit den gewaltigen zeitgleichen Depotfunden des Donauraumes zu vergleichen, deren Brucherzmassen in Einzelfallen die Tonnengrenze uberschreiten. Von wenigen Ausnahmen abgesehen tauchen [ 112 ] sie nie im Bereich der Lagerstatten im Salzburger, Kitzbuheler und Unter-inntaler Bereich auf, ein Phanomen, das seit der fruhen Bronzezeit registriert werden kann und auch am Alpensaum sind sie eher selten. Check. Massiert treten sie dagegen im Voralpenland auf, wobei der chronologische Umgriff mit jenem der Hohensiedlungen des Alpenvorlandes und des Alpenrandes ebenso kongruiert wie mit den Nordtiroler und Munchner Urnenfeldern: Das Schwergewicht liegt zwischen dem 13. On Declaration Of Independence. und dem 11. Jahrhundert. Off. Die bronzezeitliche Spatphase zwischen dem 11. Resume. und dem 9. Jahrhundert ist so gut wie nicht vertreten. Paper Check Off. Es stellen sich somit verschiedene Fragen: a) Wenn das Erz offensichtlich in with Rohform von den Lagerstatten weg verhandelt wurde, wo liegen die Verarbeitungsstatten? b) Existiert ein funktionales Netz zwischen Lagerstatten, Hohensiedlungen am Alpenrand und Hohensiedlungen des Voralpenlandes und wie ist es beschaffen? c) Was steckt hinter der Deponierung von Gusskuchen und Brucherz und warum werden sie nicht in paper check den Herkunftsgebieten deponiert? d) Besteht ein Zusammenhang zwischen dem Versiegen der Kupfervorrate in Tirol und Salzburg und dem Ende von Graberfeldern und Hohensiedlungen?

Als Trager der spatbronzezeitlichen Kultur Sudbayerns sah man lange Zeit die Bewohner einer Region des Voralpenlandes, des Riegseegebietes, an, die in 10 best resume service executives traditioneller Weise ihre Toten in off Grabhugeln bestattete. Die Wurzeln der Riegseegruppe reichen in resume die mittlere Bronzezeit und auch ihre soziale Entwicklung scheint sich eher langsam in check off kleingruppenhaften Organisationsformen zu vollziehen. Resume. [14] Dies verwundert, denn gerade wahrend der mittleren Bronzezeit nehmen die Fordermengen in check den ostalpinen Kupferbergwerken, insbesondere im Salzburger Raum stetig zu. Argumentative Essay Of Independence. [15] Obwohl in den Grabern der Riegseegruppe ab der Stufe Bz C an paper, den Schwertern die Entwicklung eines Hauptlingsadels mit kriegerischem Anspruch deutlich wird und ein aus den Beigaben ablesbarer, gewissermassen bauerlicher Wohlstand und einige Importstucke nahelegen, [16] dass die kriegerische Oberschicht an dem Mehrwert, der aus der Verarbeitung und Distribution des alpinen Kupfers herruhrte, partizipierte, fehlen doch ganzlich irgendwelche Hinweise, die auf direkte Verfugung uber Ressourcen, Werkstatten oder Verkehrswege hindeuteten. Seit Beginn der 80er Jahre tauchte im Zuge grossflachiger Grabungen auf [ 113 ] den Schotterflachen um Munchen, Ingolstadt und auf dem Lechfeld bei Augsburg eine Gruppe von Flachgrabern auf, [17] die mit den Hugelbestattungen der Riegseegruppe in 10 best resume executives ihrer Anfangsphase gleichzeitig sind, in ihrer Grundidee jedoch erheblich von diesen abweichen und eher mit jenen der fruhen Stufe der Salzburger und Tiroler Urnenfelder ubereinstimmen. Paper. [18] Wie aus dem Sachgut ersichtlich, ist die Ideenwelt der in how to write report ihnen Bestatteten vom Donau- und ostlichen Mittelmeerraum beeinflusst. Off. [19] Die sozialen und okonomischen Unterschiede zu den Bestattungen der Riegseeleute sind deutlich, wenngleich ohne Zweifel Kontakt und Austausch bestanden. Invisible. Alle bislang bekannt gewordenen Graber dieser Gruppe befinden sich an wichtigen Punkten einer naturlich vorgegebenen Verkehrsgeographie, wo sich der Handel, vornehmlich wohl jener mit Kupfererz bundelte und verzweigte und wo in Folge der Anhaufung von materiellen Gutern auch Fernbeziehungen zu sudostlichen Hochkulturen geknupft werden konnten. Paper Off. Die Eliten dieser Gruppe werden wahrend der spaten Bronzezeit archaologisch in argumentative on declaration Schachtgrabern mit Wagenbeigabe sichtbar. Check Off. [20] Bezeichnend ist die Art und Zusammensetzung, in der Grabbeigaben in invisible resume Flachgrabern der suddeutschen Spatbronzezeit niedergelegt wurden. Die Niederlegung von Gutern in check Grabern dieses Typs weicht erheblich von jenen der Hugelgraber wie von den einfachen Brandgrabern der Urnenfelder-zeit ab.

Zwar zeichnet sich in essay Grosse und Anlage des Grabschachtes noch durchaus die an paper check off, der Korperbestattung orientierte Vorstellungswelt der Hugelgraberbronzezeit ab, in argumentative essay on declaration of independence der Deponierung von verbrannten Bronzen am Rande der Grabkammern tritt jedoch ein neuer gedanklicher Kontext entgegen. Paper Check. In der Kombination von Wagenteilen, Pferdegeschirr, Waffen, Gusskuchen, Barren, Halbbfertigprodukten, Symbolgut und Geschirr ebenso wie in resume der Niederlegung auf einem Haufen scheint ein Muster auf, das auch in paper off den Horten des Donauraumes begegnet. Argumentative Essay Of Independence. [21] Massenstatistisch ist dies bis jetzt und vermutlich auch in check Zukunft nicht zu belegen, da die Exklusivitat von Grabausstattungen der beschriebenen Art dies verhindert: Nur eine dunne soziale Oberschicht konnte uber Mittel und Fernbeziehungen verfugen, die notig sind, um fremde Sachformen und neues Gedankengut aufzunehmen. Eine besondere Rolle nehmen dabei Zeugnisse der Produktion, Verarbeitung und Distribution von Metall ein. Gusskuchen, Barren und Halbfertigprodukte belegen nicht in erster Linie Besitz, sondern symbolisieren eine entscheidende Rolle der bestatteten Personengruppe bei der Forderung [ 114 ] und Verarbeitung von Metall sowie Verfugungspotential und wirtschaftliche Potenz im Handel. Invisible. So zeigen die Gewichte durch ihre geringe Grosse, dass sie nicht im Giesserei- oder Schmiedeprozess Verwendung fanden, sondern dass hier Luxusguter, also Gold, Bernstein, Kosmetika, Farbstoffe oder Gewurze eingehandelt wurden. [22] Der Mehrwert, der zum Tauschgeschaft not wendig war, durfte dabei zu einem guten Teil aus der Kontrolle uber Gewinnung, Verarbeitung und Distribution von Metall hergeruhrt haben.

Da sich die Verteilung dieser Graber mit der der Brucherzhorte und der der grossen Hohensiedlungen auf das offene Voralpenland konzentriert, kann in Beantwortung der ersten Frage also angenommen werden, dass hier auch die Verarbeitungsstatten lagen. Off. Das aus alpinen Lagerstatten gewonnene Kupfer wurde also in report Rohform ins Voralpenland gebracht, wo es in paper check den Grabern der obersten sozialen Schicht symbolischen Niederschlag fand. A Critical Essay Story. [23] Der Weg von den Lager- zu den Verarbeitungsstatten musste damit zwangslaufig an check off, den oben beschriebenen burgahnlichen Platzen des Alpenrandes vorbeifuhren, wo sich aber, mit Ausnahme der Rachelburg bei Flintsbach bisher zwar einzelne Gusskuchen oder Gusskuchenbrocken, nie jedoch grossere Horte fanden. 10 Best Resume Service. Wie oben dargelegt, mussen die Bewohner der Lagerstattenreviere, der Alpenrandburgen und der Verarbeitungsgebiete in paper check off einer nicht naher definierbaren Beziehung gestanden haben. Am starksten profitierte dabei zweifellos die neue Aristokratie des Alpenvorlandes, da nur hier in grosserem Umfang aus Fernbeziehungen resultierendes Luxusgut nachzuweisen ist. [24] Die Graber der Produktionsgebiete im Salzburger Land und in 10 best writing service Nordtirol zeigen demgegenuber zwar den durchaus betrachtlichen, jedoch eher traditionellen Wohlstand der alten Schwerttragerschicht an, der vergleichbar auch in den Grabern der Riegseegruppe sichtbar wird. Paper Check. Welcher Art die Beziehung der kleineren Burgen des Alpenrandes zu Lagerstatten und Verarbeitungsgebieten war, bleibt unklar. Invisible Resume. Nur in geringem Umfange sind aus ihrem Umkreis Graber bekannt, vornehmlich im Salzburger Becken. Check. [25] Ob sie als Aussenposten zu den Organisationen der Bergleute und Giesser gehoren, ob sie als Dependancen, quasi Ministerialensitze der voralpinen Hocharistokratie anzusehen sind oder ob sie als Punkte von Produktion, Distribution und Verarbeitung eigenstandige Teile eines Gesamtsystems sind, kann zum gegenwartigen Zeitpunkt noch nicht beantwortet werden. Die archaologische Fragestellung konnte allerdings inzwischen so zielgenau ansetzen, dass intensive Forschungen mit internationaler und interdisziplinarer, vor allen [ 115 ] Dingen naturwissenschaftlicher Beteiligung hier in a critical on a Zukunft hervorragende Ergebnisse erbringen wurden. In Beantwortung der zweiten Frage kann also die Existenz eines uber etliche Jahrhunderte wohl funktionierenden Netzes aus Leistung und Gegenleistung postuliert werden. Paper Check Off. Hierfur war eine territoriale und politische Grundordnung notig, welche die Einhaltung wirtschaftlicher Grundregeln garantierte, uber die aber bisher so gut wie nichts bekannt ist.

Zur Klarung dieses Fragenkomplexes lauft seit September 1996 am Bayer. Help Uk. Landesamt fur Denkmalpflege in paper check off Munchen eine von der Volkswagenstiftung geforderte Untersuchung zur metallurgischen Produktionskette in service Nordtirol, im Salzburger Land und im sudbayerischen Alpenvorland von der mittleren Bronzezeit bis zum Ende der Spatbronzezeit, also aus der Zeit zwischen 1600 und 800 v. Off. Chr. [26] Ziel des Projektes ist es, Aufschlusse uber die mittel- und vor allen Dingen spatbronzezeitliche Vertriebsorganisation des Kupfers aus dem Nordtiroler Inntal und Salzburger Land beziehungsweise dem Kitzbuheler Raum in invisible resume Sudbayern zu gewinnen (Abb. 3). Dabei sollen Aufschlusse uber die Gesamtdauer des bronzezeitlichen Kupferbergbaus im Nordtiroler Unterinntal und seine Hochkonjunkturphasen und Anhaltspunkte zu Konstanz und Wandel bronzezeitlicher Metallegierungen gewonnen werden. Erster Kernpunkt des Vorhabens ist das metallanalytische Programm. Paper. Es umfasst samtliche Zeugnisse der primaren Metallurgie in Sudbayern. Damit sind vor allen Dingen eine Vielzahl von Neufunden von Rohkupfer-gusskuchen aus oder in der Nahe von spatbronzezeitlichen Hohensiedlungen des Alpenrandes und des Vorlandes gemeint. Argumentative Essay On Declaration. Als Referenz wird eine reprasentative Serie von Fertigprodukten untersucht.

Dabei werden sechs regionale Gruppen unterschieden. Paper Check Off. Nordtiroler Unterinntal, Salzburger Land und Raum Kitzbuhel, sudwestliches Oberbayern bis zum Inntal, ostliches Oberbayern, ferner der Donauraum, unterschieden in Ingolstadter und Kelheimer Donauraum einerseits und Regensburger Donauraum und ostliches Niederbayern andererseits. 10 Best Resume Writing. Von besonderem Interesse sind dabei wegen der darin enthaltenen Gusskuchen und Barren die Bronzen aus den spatbronzezeitlichen Wagengrabern. Wir legen Wert darauf, dass die Beprobung der Kupfervorkommen in Bereichen erfolgt, die auch in der Bronzezeit fur die Ausbeutung erreichbar waren. Off. In der Regel wird dies die Ausbisszone des Erzkorpers sein. Am Mitterberg und im Gebiet Schwaz-Brixlegg konnen die Proben direkt aus bronzezeitlich datierten Abbauen entnommen werden. Invisible Resume. [ 116 ] Die Erzproben werden auf bestimmte Elementkombinationen hin untersucht, die auch noch im Fertigprodukt nachweisbar sind. Paper Check. Neben den in 10 best writing jedem Fall zu bestimmenden Gehalten an check off, Zinn, Wismut, Arsen, Nickel und Silber sollen dabei auch Spurenelemente wie Gold, Uran oder Blei analysiert werden. A Critical Essay On A Short. Sinnvolle Erganzung zu den chemischen Erzanalysen sind erzmikroskopische Untersuchungen, da nur so die Erzmineralparagenese bestimmt werden kann. Paper. Das unterschiedliche Austreten von akzessorischen Erzmineralien (zum Beispiel Kupfernickelerzen) beeinflusst nicht nur den Pauschalchemismus der Erze, sondern ist oft auch eine charakteristische Eigenheit einzelner Vorkommen. Write Report Example. Grundlage der bronzezeitlichen Kupferproduktion im Nordtiroler Inntal sind die Fahlerze des Unterinntals, die sich durch hohe Anteile an off, Antimon, Arsen, Silber und Wismut pragnant charakterisieren lassen. Innerhalb des Untersuchungsgebietes sollte deswegen die Verbreitung Nordtiroler Fahlerzkupfers sowohl in den Rohkupfergusskuchen als auch in den Fertigprodukten direkt fassbar sein.

Die Kupfersorten aus den Erzen des Salzburger Landes und die Kupferkiese des Raumes Kitzbuhel sind zwar durch ihre relative Armut an Spurenelementen eher uncharakteristisch, kontrastieren aber insgesamt scharf mit dem Tiroler Fahlerzkupfer. Help With Assignments Uk. Aus diesem Kontrast erwarten wir jedenfalls im engeren Vorfeld der Bergbaugebiete auch die Verbreitung des Salzburger/Kitzbuheler Kupfers umreissen zu konnen. Ausgehend von der naturlichen Verkehrsgeographie folgen wir dabei der Arbeitshypothese, dass Nordtiroler Fahlerzkupfer hauptsachlich uber das westliche Oberbayern verhandelt und verarbeitet wurde, wahrend Salzburger und Kitzbuheler Kupfer uber Salzach und Alz nach Norden gelangte. Paper Check Off. Das erstere dieser Gebiete wird definiert durch das Wagengrab des spaten 13. A Interview. vorchristlichen Jahrhunderts von Poing bei Munchen, das zweite durch jenes des fruhen 12. Jahrhunderts von Hart an der Alz. Check. [27] Erstmals sind damit Ergebnisse zur politischen und territorialen Organisation der Bronzezeit in writing short story Sudbayern zu erwarten. Paper. Die dritte Frage lautete: Was steckt hinter der Deponierung von Gusskuchen und warum wurden sie nicht in den Herkunftsgebieten deponiert? Wenn im vorhergehenden festgestellt wurde, dass in how to write den Herkunftsgebieten des Kupfers kaum Brucherzhorte nachweisbar sind, so kann dies nicht bedeuten, dass das Kupfer den dort ansassigen Gruppen nicht zur Verfugung gestanden hatte. Wie die Graber der Nordtiroler Urnenfelder oder des Salzburger Raumes zeigen, wurde hier sogar betrachtlicher Wohlstand akkumuliert. Check. [ 117 ] Abb. Invisible. 3: Ubersichtskarte zu dem von der Volkswagenstiftung geforderten Forschungsprojekt des bayerischen Landesamtes fur Denkmalpflege, Abt fur Archaologische Denkmalpflege. Umrandet sind die geographisch-kulturell umrissenen Beprobungsbezirke (1A Tiroler Inntal, 1B Salzburger und Kitzbuheler Bereich, 2A westliches Oberbayern mit Munchner Schotter ebene, 2B ostliches Oberbayern, 3A Ingol-stadter Donaubereich, 3B Oberpfalzer Senke, Gauboden und niederbayerisches Hugelland) und schraffiert die Lagerstattenreviere dargestellt Punkte: Fundorte der beprobten Stucke; Dreiecke: Hohensiedlungen am Alpenrand; Radkreuze: Fundorte von Wagengrabern der Spatbronze- und Urnenfelder zeit. [ 118 ] zu dessen Reprasentation jedoch nicht die Niederlegung von Horten gehorte.

Die mit den neuen Bestattungssitten verbundene Vorstellungswelt blieb der Bergbau treibenden, alpinen Bevolkerung im Gegensatz zu den Eliten des Voralpenlandes fremd. Paper. Nur bei jenen deckt sich die Verbreitung von Horten, grabschatzfuhrenden Grabern mit danubisch-agaischem Einfluss und befestigten Hohensiedlungen der Spatbronze grossraumig ebenso wie die jenige von Horten und Burgen der Donaulander. Aus den Donaulandern gelangten Vorstellungen, die mit der Deponierung grosser Bronzehorte gemischten Inhalts verbunden sind, im Zuge verstarkter Fernkontakte zusammen mit zahlreichen Sachgutern nach Suddeutschland, wo sie von einem progressiven Teil der einheimischen Eliten in essay on advertising is a uberkommene Bestattungsmuster ubernommen wurde. Paper. Der Lebensstil und die soziologische Basis dieser Eliten ist in resume den Landern entlang der Donau durchaus vergleichbar, wie Art und Topographie der Befestigungen verraten, und resultiert zum uberwiegenden Teil aus der Verarbeitung und Verteilung von bergmannisch gewonnenem Kupfer. Die spezielle Ausstattung der nord-alpinen Wagengraber ware als direkte Ubernahme ostmitteleuropaischer Deponierungssitten in das im Umbruch befindliche traditionelle Totenritual der westlichen Hugelgraberkultur zu sehen, eine Ubernahme, die wahrscheinlich auch von neuen religiosen Vorstellungen begleitet war. [28] Die letzte Frage lautete: Besteht ein Zusammenhang zwischen dem Versiegen der Kupfervorrate in check Tirol und Salzburg und dem Ende von Graberfeldern und Hohensiedlungen dort und in how to a interview report Sudbayern? Die Nordtiroler Urnenfelder, die Urnenfelder des Munchener Bereiches ostlich der Isar sowie die Hohensiedlungen des Alpenvorlandes und des Alpenrandes brechen nach gegenwartigem Kenntnisstand in paper check off einem fruhen Abschnitt der Urnenfelderstufe B, als kurz nach dem Jahr 1000 v. 10 Best Resume Writing Service. Chr. Check Off. ab. Invisible Resume. Man nimmt dafur ein Versiegen der leicht ausbeutbaren Kupfervorkommen der Ostalpen insgesamt an.

Einzelne, sehr wohlhabende Graberfelder zeigen jedoch, dass auch nach der Erschopfung der Kupfervorkommen wohlhabende Gemeinwesen am Alpenrand existierten, deren Wirtschaftsgrundlage unklar ist (vielleicht gelang es ihnen vom Kupferhandel auf denjenigen mit Hallstatter Salz umzusteigen). Paper Off. [29] Aufschlusse zu diesem Fragenkomplex sind vornehmlich uber die Metallanalytik zu erwarten: Ist beispielsweise das Abbrechen der Nordtiroler Urnenfelder tatsachlich auf einen schweren Einbruch des Kupferbergbaus im Nordtiroler Unterinntal zuruck zufuhren, so musste synchron dazu oder mit einer gewissen Verzogerung in [ 119 ] Sudbayern ein massiver Ruckgang im Gebrauch des Fahlerzkupfers festzustellen sein. Noch nicht abgeklart ist ferner die wirtschaftliche Bedeutung des Kupferbergbaues im Nordtiroler Unterinntal. Sollte er lediglich regionale Bedeutung fur Nordtirol und das sudliche Oberbayern besessen haben, musste der Fahlerzkupfers trom bereits in on advertising necessary der Donauregion versickern. Paper Check. Zeichnet er sich aber dort noch massiv ab, reichte er sicherlich auch daruber hinaus und signalisiert die uberregionale Bedeutung der Unterinntaler Kupferproduktion, die aufgrund der bisherigen Indizien fur die spate Bronze- und fruhe Urnen-felderzeit auch wahrscheinlich ist. Hangen aber die Hohensiedlungen des sudbayerischen Raumes von der Produktion, Distribution und Verarbeitung von Kupfer ab, so musste ihre wirtschaftliche und politische Rolle fur ganz Suddeutschland parallel verlaufen. How To A Interview Report. Mit einiger Wahrscheinlichkeit bedingte die Ausbeutung und Verarbeitung der ostalpinen Lagerstatten politisch-okonomische Systeme mit ahnlich uberregional wirksamer Rolle wie weiter im Westen diejenigen der Schweiz und Vorarlbergs. 1 Der hier publizierte Vortrag wurde in ahnlicher Form auf dem Niederbayerischen Archaologentag 1997 in check Deggendorf gehalten und ist weitgehend gleichlautend veroffentlicht in: K. Schmotz (Flg.), Vortrage des 16. Niederbayerischen Archaologentages . Writing A Critical On A Short Story. Deggendorf 1997, S. 99-113. Paper Off. 2 Ansatze der 50er Jahre, u. On A Story. a. Off. Flans-Jurgen Flundt, «Der Bogenberg bei Bogen (Niederbayern) in vor- und fruhgeschichtlicher Zeit», in: Bayerische Vorgeschichtsblatter 21,1955, S. 10 Best Resume Writing Service Executives. 31-46 und Fiermann Muller-Karpe, «Funde von bayerischen Hohensiedlungen», in: Kataloge der Prahistorischen Staatssammlung Munchen 3, Kallmunz 1954, wurden nicht konsequent weiterverfolgt und erst in den letzten Jahren wieder in off verstarktem Umfang auf gegriffen: Jorg Biel, Vorgeschichtliche Hohensiedlungen in 10 best resume writing service Sudwurttemberg-Hohenzollern . Paper Check Off. Forschungen und Berichte zur Vor- und Fruhgeschichte in help with uk Baden-Wurttemberg 24, Stuttgart 1987.

Albrecht Jockenhovel, «Jungerbronzezeitlicher Burgenbau in paper check Suddeutschland», in: Beitrage zum bronzezeitlichen Burgenbau in Mitteleuropa. Berlin 1984, S. Invisible. 253-272. Ders., «Bronzezeitlicher Burgenbau in paper Mitteleuropa. Invisible. Untersuchungen zur Struktur fruhmetallzeitlicher Gesellschaften», in: Orientalisch-agaische Einflusse in check der europaischen Bronzezeit . 10 Best Resume Service Executives. Monographien des Romisch-Germanischen Zentralmuseums Mainz, Mainz 1990, S. Paper Off. 209-228. Essay On Declaration. Peter Schauer, «Befestigte Hohen der Urnenfelderzeit und der alteren Eisenzeit in check off Suddeutschland», in: Hermann Dannheimer, Rupert Gebhard (Hg.), Das keltische Jahrtausend.

Mainz 1993, S. On Advertising Is A Necessary Evil. 62-74. Ders., Folke Damminger, «Der Bogenberg im Landkreis Straubing-Bogen, Niederbayern. Vorbericht uber die archaologischen Untersuchungen der Jahre 1995-1996», in: Archaologisches Korrespondenzblatt 27,1997, S. Paper. 423-442. Invisible Resume. Ubergreifend zum Thema der donaulandischen und suddeutschen Burgen: Stefan Winghart, «Sudbayern und der Donauraum - Aspekte zum Thema der spatbronze - und fruhurnenfelderzeitlichen Hohensiedlungen entlang der Donau», in: The Early Hall- [ 120 ] statt Period (1200-700 B. C.) in South-Eastern Europe . Bibliotheca Musei Apulensis, Alba Iulia 1994, S. Paper Off. 241-253. 3 Zusammenfassend fur den siebenburgischen Raum:Tiberiu Bader, «Die befestigten bronzezeitlichen Siedlungen in essay on declaration Nordwestrumanien» in: Beitrage zum bronze zeitlichen Burgenbau in paper Mitteleuropa , Berlin 1984, S. Help Uk. 47-70. Fur Ungarn: Gabor Bandi, «Bronzezeitliche befestigte Siedlungen in off Westungarn» in: Ebd. , S. Help With Assignments Uk. 81-95. Paper Check Off. Tibor Kemenczei, «Der spatbronzezeitliche Burgenbau in argumentative essay Nordungarn», in: Ebd. , S. 273-278.

Fur die Slowakei: Vaclav Furmanek, Ladislav Veliacik, Peter Romsauer, «Jungbronzezeitliche befestigte Siedlungen in der Slowakei», in: Ebd ., S. Check Off. 159-175. Fur dieses Thema von besonderer Bedeutung: Kurt Floredt, «Befestigte Siedlungen der Spatbronzezeit im innerkarpatischen Raum», in: Symposium zu Problemen der jungeren Hallstattzeit in invisible Mitteleuropa. Off. Bratislava 1974, S. Resume Service Executives. 205-228. 4 Bis in die 70er Jahre lediglich: Fritz-Rudolf Flerrmann, «Die urnenfelderzeitliche Siedlung von Kunzing», in: Jahresberichte der bayerischen Bodendenkmalpflege 15/16, 1974/75, S. 58-107. Check Off. Seitdem ist eine nahezu unubersehbare Menge metallzeitlicher Flausgrundrisse und Siedlungskontexte erschlossen worden, die derzeit im Rahmen zweier Munchner Dissertationen aufgearbeitet werden. Write A Interview Example. Vorberichte fur das Schotterfeld um Munchen: Stefan Winghart, «Eine Siedlung der Urnenfelder- oder Flallstattzeit von Eching, Lkr. Freising, Oberbayern», in: Das archaologische Jahr in Bayern 1983, S. Off. 65-67. Ingeborg von Quillfeldt, «Eine Siedlung der Spatbronzezeit in essay necessary Gauting, Lkr. Starnberg, Oberbayern», in: Das archaologische Jahr in Bayern 1988, S. 53-56. Paper Check. Fur das Schotterfeld um Ingolstadt: Marc Bankus, «Fruhe und mittlere Bronzezeit», in: Karl-Heinz Rieder, Andreas Tillmann (Hg.), Archaologie um Ingolstadt, Kipfenberg 1995, S. 53-88. Cornelia Schutz-Tillmann, «Spate Bronzezeit und Urnenfelderzeit», in: Ebd. Essay On Advertising. , S. Paper Off. 89-112.

Fur das Lechfeld um Augsburg: Stefan Wirth, «Die Urnenfelderzeit», in: Walter Potzl, Otto Schneider (Hg.), V or- und Fruhgeschichte-Archaologie einer Landschaft. Der Landkreis Augsburg, Bd. 2, Augsburg 1996, S. 11-139. 5 Michael Schefzik, «Neuartige Funde und Befunde endneolithisch-alterfruhbronzezeitlicher Zeitstellung von Eching, Lkr. On Declaration. Freising», in: Bayerische Vorgeschichtsblatter 60,1995, S. Off. 273-287.

Michael Schefzik und Robert Ganslmeier, «Freiham - Siedlung und Graberfeld der fruhen Bronzezeit, Landeshauptstadt Munchen, Oberbayern», in: Das archaologische Jahr in Bayern 1996, S. Invisible. 61-63. Check. Im weiteren vergleiche Bankus (wie Anm. How To Write Report. 4). Check. 6 Stefan Winghart, «Bemerkungen zu Genese und Struktur fruhmittelalterlicher Siedlung im Munchner Raum», in: Lothar Kollmer, Peter Segl (Hg.), Regensburg, Bayern und Europa. Festschrift fur Kurt Reindel zu seinem 70.

Geburtstag, Regensburg 1995, S. 7-49. With Uk. 7 Vgl. Paper Check Off. Muller-Karpe (wie Anm. 10 Best Resume. 2). Paper Check. 8 Muller-Karpe (wie Anm. 2), S. Resume Writing Executives. 7, 14 Taf. 1, S. Off. 12-15, 20-27, 30-39. Essay. 9 Zum Nachweis vgl., Winghart 1994 (wie Anm. Check Off. 2), S. Resume. 242 mit Anm. Paper Check Off. 13-18. 10 Tudor Soroceanu, «Hortfunde und befestigte Anlagen in Transsilvanien», in: Beitrage zum bronzezeitlichen Burgenbau in Mitteleuropa , Berlin 1984, S. 363-376.

Furmanek/Veliacik/Romsauer (wie Anm. Necessary. 3). Maria Novotna, Die Bronzehortfunde in paper check off der Slowakei. Spatbronzezeit. Is A. Bratislava 1970, S. Paper Check. 18, Karte 1. 11 Hansjorg Kuster et al., «Beitrage zur vor- und fruhgeschichtliche Hohensiedlung Rachel-burg uber dem nordlichen Alpeninntal bei Flintsbach, Lkr. Rosenheim, Oberbayern», in: Berichte der Bayerischen Bodendenkmalpflege 38/39, 1997/98 im Druck.

Vorbericht: Stefan Winghart, «Halsschmuck der fruhen Mittelbronzezeit von der Hohensiedlung Rachelburg bei Flintsbach am Inn, Lkr. Resume Writing Executives. Rosenheim, Oberbayern» in: Das archaologische Jahr in paper check off Bayern 1993, S. Argumentative On Declaration. 62-65. 12 Vgl. Christin Osterwalder-Maier, «Bronzezeitliche Gesellschaft - Ein homerisches Modell», in: Gesellschaft und Bevolkerung. Paper Check Off. Schweizerische Gesellschaft fur Ur- und Fruhgeschichte , Bern 1990, S. 10 Best Resume Writing Executives. 85-92, bes.

S. 88. Paper Check. 13 Frauke Stein, «Bronzezeitliche Hortfunde in essay Suddeutschland», in: Saarbrucker Beitrage zur Altertumskunde 23, Bonn 1976, S. 66-70. Check Off. [ 121 ] 14 Harald Koschik, Die Bronzezeit im sudwestlichen Oberbayern . Materialhefte zur bayerischen Vorgeschichte 50, Kallmunz 1981, S. 133-143. Essay Is A Necessary. 15 Fritz Moosleitner, «Vier Spangenbarrendepots aus Obereching, Land Salzburg», in: Germania 66,1988, S. Paper Check. 29-67. 16 Rudolf Albert Maier, «Sicherungsgrabungen in how to write Hugelgrabern der Mittleren Bronzezeit im Alztal», in: Neue Ausgrabungen in Bayern («Probleme der Zeit»), Munchen 1970, S. Off. 14-17ff. Harald Koschik, «Das bronzezeitliche Graberfeld von Unterbrunnham», in: Fuhrer zu vor- und fruhgeschichtlichen Denkmalern 19, Mainz 1971, S. Essay On Declaration Of Independence. 64-68. Check Off. Stephan Moslein, Bronze- und Urnenfelderzeit im ostlichen Oberbayern. Ungedr.

Diss., Munchen 1996 passim. Resume. 17 Stefan Winghart, «Flachgraber der spaten Bronzezeit aus Eching und Geisenfeld-Ilmendorf, Landkreise Freising und Pfaffenhofen a. Check. d. Help Assignments Uk. Ilm, Oberbayern», in: Das archaologische Jahr in Bayern 1992, S. 54-56. Ders., «Das Wagengrab von Poing und der Beginn der Urnenfelderzeit in paper check Sudbayern», in: Hermann Dannheimer, Rupert Gebhard (Hg.), Das keltische Jahrtausend. Mainz 1993, S. 88-93. 18 Karl-Heinz Wagner, Nordtiroler Urnenfelder. Romisch-Germanische Forschungen 15, Berlin 1943. Zum Thema zuletzt mit alterer Literatur Peter Hoglinger, «Die Bronzezeit im Salzburger Flachgau», in: Archaologie beiderseits der Salzach. 10 Best Resume Writing Service. Salzburg 1996, S. Paper Off. 34 -48. 19 Stefan Winghart, «Die Wagengraber von Poing und Hart a. Essay On A. d. Paper Off. Alz - Evidenz und Ursachen spatbronzezeitlicher Elitenbildung in der Zone nordwarts der Alpen», in: Eliten in invisible der Bronzezeit.

Monographien des Romisch-Germanischen Zentralmuseums Mainz , Mainz 1998 (im Druck). Paper. 20 Zuletzt ubergreifend: Christopher F. E. Assignments Uk. Pare, Wagons and check off Wagon Graves of the Early Iron Age in a critical essay short Central Europe . Paper. Oxford Monographs 35, Oxford 1992, S. 19-42. 21 Winghart 1994 (wie Anm. 2), S. On Declaration Of Independence. 248 ff. Off. 22 Eine ubergreifende Behandlung des Themas durch Christopher F. A Interview Example. E. Pare ist in paper off Vorbereitung. Is A Necessary Evil. Fur Sudbayern ein diesbezuglicher Neufund: Stefan Winghart, «Totenfolge am Lechrain? Ein reiches Doppelgrab der spaten Bronzezeit im neu entdeckten Graberfeld von Hurlach, Lkr.

Landsberg am Lech, Oberbayern», in: Das archaologische Jahr in paper off Bayern 1996, S. 10 Best Resume. 69-72. Bisher unpubliziert sind zwei Gewichte aus der spatbronzezeitlichen Adelsnekropole von Poing. Check Off. Lkr. With Assignments Uk. Ebersberg, Bayern (vgl. Check. Winghart 1993, Anm. 17). Write A Interview Report. 23 Winghart 1993 (wie Anm. Paper. 17). Albrecht Jockenhovel, «Urnenfelderzeitliche Barren als Grabbeigabe», in: Archaologisches Korrespondenzblatt 3, 1973, S. Executives. 23-28. Ders., «Zeugnisse primarer Metallurgie in paper check Grabern der Bronze- und Alteisenzeit Mitteleuropas», in: Archaeologia Polski 27, 1982, 293-301. 24 Nur am Rande soll in invisible resume diesem Zusammenhang auf den uberaus komplizierten Komplex des Zinnhandels verwiesen werden: Zinn, das zur Legierung der Bronze notwendig ist, kommt nicht in paper check selben Lagerstattenrevieren wie Kupfer vor und musste demzufolge eingehandelt werden.

Nach dem aufgefuhrten Modell trafen die Kupfer- und Zinnstrome in argumentative on declaration Suddeutschland in check den Wohnsitzen der voralpinen Aristokratie zusammen. Writing. 25 Hoglinger (wie Anm. Paper Off. 18). Write A Interview. 26 Das von Dr. L. Sperber, Historisches Museum der Pfalz, Speyer und dem Verfasser for mulierte und beantragte Projekt wurde 1996 im Rahmen des Forschungsschwerpunktes «Archaeometallurgie» der Volkswagenstiftung genehmigt. Die Durchfuhrung im Bayerischen Landesamt fur Denkmalpflege, Abt. Paper Check Off. fur Archaologische Denkmalpflege, Munchen erfolgt durch Dr. Stephan Moslein, die Metallanalytik durch Prof. Writing On A Short Story. Dr. Ernst Pernicka, Max-Planck-Institut fur Kernphysik, Heidelberg und die lagerstattenkundlichen Unter-suchungen durch Dipl.

Min. Paper Check. Klaus-Peter Martinek, Zwiesel. Die Publikation der Ergebnisse ist fur die Arbeitshefte des Bayerischen Landesamtes fur Denkmalpflege vorgesehen. 27 Hermann Muller-Karpe, «Das urnenfelderzeitliche Wagengrab von Hart a. On Advertising. d. Paper Check Off. Alz», in: Bayerische Vorgeschichtsblatter 21, 1955, S. Resume. 46-75. Check. 28 Vgl. Resume Service. hierzu etwa Walter Janssen, «Der Bullenheimer Berg», in: Hermann Dannheimer, Rupert Gebhard (Hg.), Das keltische Jahrtausend . Munchen 1993, S. Check Off. 75-82, wo Hortfunde [ 122 ] innerhalb einer befestigten Hohensiedlung als Tempelschatze angesprochen werden. On Advertising Necessary. Ubergreifend zum Thema: Joachim Werner, «Mykenae - Siebenburgen - Skandinavien», in: Atti del primo congresso internazionale di preistoria e protostoria mediterranea . Check. Firenze, Napoli, Roma 1950, S. Argumentative Essay Of Independence. 293-308. Kurt Horedt, «Siebenburgen und Mykena», in: Nouvelles Etudes d’Histoire, publiees a l’occasion du Xle congres des sciences historiques . Check. Stockholm 1969, S. 10 Best Writing Executives. 31-44.

29 Fritz Moosleitner, «Rettungsgrabung in paper Salzburg-Maxglan», in: Archaologie Osterreichs 4/2, 1993, S. Help With Assignments. 10-20: Ders., «Kelten in paper Flachgau», in: Archaologie beiderseits der Salzach , Salzburg 1996, S. Help Assignments. 60-74.

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Enzymes: principles and biotechnological applications. Enzymes are biological catalysts (also known as biocatalysts) that speed up biochemical reactions in living organisms, and off, which can be extracted from cells and then used to catalyse a wide range of commercially important processes. This chapter covers the basic principles of resume enzymology, such as classification, structure, kinetics and inhibition, and also provides an overview of industrial applications. In addition, techniques for the purification of enzymes are discussed. Enzymes are biological catalysts (also known as biocatalysts) that speed up biochemical reactions in living organisms. They can also be extracted from check off, cells and then used to catalyse a wide range of writing story commercially important processes. For example, they have important roles in the production of sweetening agents and the modification of antibiotics, they are used in washing powders and various cleaning products, and they play a key role in analytical devices and paper check off, assays that have clinical, forensic and environmental applications. The word ‘enzyme’ was first used by the German physiologist Wilhelm Kuhne in 1878, when he was describing the ability of yeast to produce alcohol from sugars, and it is derived from the a interview Greek words en (meaning ‘within’) and paper check, zume (meaning ‘yeast’). In the late nineteenth century and on advertising necessary, early twentieth century, significant advances were made in the extraction, characterization and commercial exploitation of many enzymes, but it was not until the 1920s that enzymes were crystallized, revealing that catalytic activity is associated with protein molecules.

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The remaining digits have different meanings according to the nature of the reaction identified by check, the first digit. For example, within the oxidoreductase category, the second digit denotes the how to report example hydrogen donor (Table 3) and check, the third digit denotes the hydrogen acceptor (Table 4). Thus lactate dehydrogenase with the writing short story EC number 1.1.1.27 is an oxidoreductase (indicated by the first digit) with the paper check off alcohol group of the lactate molecule as the hydrogen donor (second digit) and NAD + as the hydrogen acceptor (third digit), and is the 27th enzyme to assignments be categorized within this group (fourth digit). Fortunately, it is now very easy to find this information for check, any individual enzyme using the Enzyme Nomenclature Database (available at http://enzyme.expasy.org). Enzyme structure and substrate binding. Amino acid-based enzymes are globular proteins that range in size from less than 100 to more than 2 000 amino acid residues. These amino acids can be arranged as one or more polypeptide chains that are folded and bent to form a specific three-dimensional structure, incorporating a small area known as the active site (Figure 1), where the substrate actually binds. The active site may well involve only a small number (less than 10) of the constituent amino acids. It is the shape and charge properties of the active site that enable it to help with assignments uk bind to a single type of substrate molecule, so that the enzyme is able to demonstrate considerable specificity in its catalytic activity.

The hypothesis that enzyme specificity results from the complementary nature of the substrate and paper, its active site was first proposed by help uk, the German chemist Emil Fischer in 1894, and paper off, became known as Fischer's ‘lock and help assignments uk, key hypothesis’, whereby only paper check off, a key of the service correct size and shape (the substrate) fits into the keyhole (the active site) of the lock (the enzyme). Check Off? It is astounding that this theory was proposed at a time when it was not even established that enzymes were proteins. Writing A Critical Essay Short? As more was learned about enzyme structure through techniques such as X-ray crystallography, it became clear that enzymes are not rigid structures, but are in fact quite flexible in shape. In the light of this finding, in 1958 Daniel Koshland extended Fischer's ideas and presented the ‘induced-fit model’ of substrate and paper off, enzyme binding, in which the enzyme molecule changes its shape slightly to accommodate the binding of the substrate. The analogy that is commonly used is the ‘hand-in-glove model’, where the hand and on advertising is a necessary, glove are broadly complementary in shape, but the glove is moulded around the hand as it is inserted in order to paper off provide a perfect match. Since it is the active site alone that binds to is a necessary the substrate, it is logical to ask what is the paper off role of the rest of the protein molecule.

The simple answer is that it acts to stabilize the active site and provide an appropriate environment for interaction of the 10 best resume writing service executives site with the substrate molecule. Therefore the active site cannot be separated out from the rest of the protein without loss of catalytic activity, although laboratory-based directed (or forced) evolution studies have shown that it is sometimes possible to paper generate smaller enzymes that do retain activity. It should be noted that although a large number of resume enzymes consist solely of protein, many also contain a non-protein component, known as a cofactor, that is paper necessary for the enzyme's catalytic activity. A cofactor may be another organic molecule, in help, which case it is called a coenzyme, or it may be an inorganic molecule, typically a metal ion such as iron, manganese, cobalt, copper or zinc. Off? A coenzyme that binds tightly and permanently to the protein is generally referred to as the prosthetic group of the enzyme. When an enzyme requires a cofactor for its activity, the inactive protein component is generally referred to as an apoenzyme, and the apoenzyme plus the report cofactor (i.e. the active enzyme) is off called a holoenzyme (Figure 2).

The need for minerals and vitamins in the human diet is partly attributable to invisible their roles within metabolism as cofactors and coenzymes. How do enzymes work? The broad answer to check this question is that they do not alter the equilibrium (i.e. the thermodynamics) of a reaction. This is because enzymes do not fundamentally change the structure and energetics of the products and on declaration of independence, reagents, but rather they simply allow the reaction equilibrium to be attained more rapidly. Let us therefore begin by clarifying the off concept of chemical equilibrium. In many cases the equilibrium of a reaction is invisible far ‘to the right’—that is, virtually all of the paper substrate (S) is converted into product (P). For this reason, reactions are often written as follows: This is a simplification, as in all cases it is more correct to write this reaction as follows: This indicates the presence of an equilibrium.

To understand this concept it is perhaps most helpful to look at a reaction where the equilibrium point is quite central. In this reaction, if we start with a solution of 1 mol l ?1 glucose and add the enzyme, then upon completion we will have a mixture of approximately 0.5 mol l ?1 glucose and 0.5 mol l ?1 fructose. Help Assignments? This is the equilibrium point of this particular reaction, and although it may only take a couple of seconds to reach this end point with the enzyme present, we would in fact come to the same point if we put glucose into solution and waited many months for the reaction to paper check occur in the absence of the enzyme. Interestingly, we could also have started this reaction with a 1 mol l ?1 fructose solution, and argumentative on declaration of independence, it would have proceeded in the opposite direction until the same equilibrium point had been reached. The equilibrium point for this reaction is expressed by the equilibrium constant K eq as follows: Thus for a reaction with central equilibrium, K eq = 1, for an equilibrium ‘to the paper check right’ K eq is 1, and for an equilibrium ‘to the assignments left’ K eq is 1. Therefore if a reaction has a K eq value of 10 6 , the equilibrium is very far to the right and can be simplified by denoting it as a single arrow. Check Off? We may often describe this type of reaction as ‘going to completion’. Help Uk? Conversely, if a reaction has a K eq value of 10 ?6 , the equilibrium is very far to paper the left, and for all practical purposes it would not really be considered to proceed at all. It should be noted that although the concentration of essay reactants has no effect on the equilibrium point, environmental factors such as pH and temperature can and do affect the position of the equilibrium. It should also be noted that any biochemical reaction which occurs in vivo in a living system does not occur in isolation, but as part of a metabolic pathway, which makes it more difficult to conceptualize the relationship between reactants and check, reactions.

In vivo reactions are not allowed to proceed to resume their equilibrium position. Off? If they did, the reaction would essentially stop (i.e. the forward and reverse reactions would balance each other), and argumentative essay on declaration, there would be no net flux through the pathway. However, in paper check off, many complex biochemical pathways some of the individual reaction steps are close to equilibrium, whereas others are far from resume, equilibrium, the latter (catalysed by regulatory enzymes) having the greatest capacity to control the overall flux of paper check materials through the pathway. Enzymes form complexes with their substrates. We often describe an enzyme-catalysed reaction as proceeding through three stages as follows: The ES complex represents a position where the substrate (S) is bound to the enzyme (E) such that the reaction (whatever it might be) is made more favourable. As soon as the essay on a short reaction has occurred, the check product molecule (P) dissociates from the enzyme, which is then free to bind to 10 best resume writing service executives another substrate molecule.

At some point during this process the substrate is converted into an intermediate form (often called the transition state) and then into paper check the product. The exact mechanism whereby the enzyme acts to increase the rate of the reaction differs from one system to another. However, the general principle is that by binding of the substrate to the enzyme, the reaction involving the substrate is made more favourable by lowering the activation energy of the reaction. In terms of energetics, reactions can be either exergonic (releasing energy) or endergonic (consuming energy). However, even in an exergonic reaction a small amount of energy, termed the activation energy, is needed to give the reaction a ‘kick start.’ A good analogy is that of a match, the head of which contains a mixture of energy-rich chemicals (phosphorus sesquisulfide and potassium chlorate). When a match burns it releases substantial amounts of light and invisible, heat energy (exergonically reacting with O 2 in paper check, the air). However, and perhaps fortunately, a match will not spontaneously ignite, but rather a small input of energy in the form of heat generated through friction (i.e. striking of the match) is needed to initiate the reaction. Of course once the match has been struck the amount of help with uk energy released is paper off considerable, and greatly exceeds the small energy input during the striking process. As shown in Figure 3, enzymes are considered to lower the writing executives activation energy of a system by making it energetically easier for the transition state to form.

In the check off presence of an enzyme catalyst, the formation of the transition state is energetically more favourable (i.e. it requires less energy for the ‘kick start’), thereby accelerating the rate at which the reaction will proceed, but not fundamentally changing the energy levels of either the reactant or the product. Properties and help assignments, mechanisms of enzyme action. Enzyme kinetics is the study of factors that determine the speed of enzyme-catalysed reactions. It utilizes some mathematical equations that can be confusing to students when they first encounter them. Check? However, the theory of kinetics is both logical and simple, and it is essential to develop an understanding of this subject in order to assignments uk be able to appreciate the role of paper enzymes both in metabolism and in biotechnology. Assays (measurements) of enzyme activity can be performed in either a discontinuous or continuous fashion. Discontinuous methods involve mixing the substrate and enzyme together and write report example, measuring the product formed after a set period of time, so these methods are generally easy and quick to check perform. In general we would use such discontinuous assays when we know little about the system (and are making preliminary investigations), or alternatively when we know a great deal about the system and are certain that the time interval we are choosing is appropriate. In continuous enzyme assays we would generally study the rate of an enzyme-catalysed reaction by mixing the enzyme with the substrate and continuously measuring the appearance of product over time. Of course we could equally well measure the rate of the reaction by with assignments uk, measuring the disappearance of substrate over time. Apart from the actual direction (one increasing and one decreasing), the two values would be identical.

In enzyme kinetics experiments, for convenience we very often use an paper, artificial substrate called a chromogen that yields a brightly coloured product, making the reaction easy to follow using a colorimeter or a spectrophotometer. However, we could in fact use any available analytical equipment that has the capacity to measure the concentration of either the product or the substrate. In almost all cases we would also add a buffer solution to the mixture. As we shall see, enzyme activity is strongly influenced by pH, so it is writing a critical essay on a short story important to check set the pH at a specific value and keep it constant throughout the experiment. Our first enzyme kinetics experiment may therefore involve mixing a substrate solution (chromogen) with a buffer solution and adding the writing a critical essay on a story enzyme. This mixture would then be placed in a spectrophotometer and the appearance of the paper off coloured product would be measured. This would enable us to essay on advertising is a necessary follow a rapid reaction which, after a few seconds or minutes, might start to slow down, as shown in Figure 4. A common reason for this slowing down of the speed (rate) of the reaction is off that the substrate within the mixture is being used up and thus becoming limiting. Alternatively, it may be that the enzyme is unstable and is denaturing over the course of the experiment, or it could be that the pH of the mixture is changing, as many reactions either consume or release protons.

For these reasons, when we are asked to 10 best service specify the rate of a reaction we do so early on, as soon as the enzyme has been added, and when none of the above-mentioned limitations apply. We refer to this initial rapid rate as the initial velocity ( v 0 ). Measurement of the reaction rate at this early stage is also quite straightforward, as the rate is effectively linear, so we can simply draw a straight line and check off, measure the writing a critical story gradient (by dividing the concentration change by off, the time interval) in order to evaluate the reaction rate over this period. We may now perform a range of invisible similar enzyme assays to evaluate how the off initial velocity changes when the substrate or enzyme concentration is altered, or when the pH is changed. These studies will help us to characterize the properties of the resume writing service executives enzyme under study. The relationship between enzyme concentration and the rate of the reaction is usually a simple one.

If we repeat the experiment just described, but add 10% more enzyme, the paper off reaction will be 10% faster, and if we double the enzyme concentration the reaction will proceed twice as fast. Thus there is a simple linear relationship between the reaction rate and the amount of enzyme available to catalyse the reaction (Figure 5). This relationship applies both to enzymes in vivo and to those used in biotechnological applications, where regulation of the amount of enzyme present may control reaction rates. When we perform a series of enzyme assays using the same enzyme concentration, but with a range of 10 best resume executives different substrate concentrations, a slightly more complex relationship emerges, as shown in Figure 6. Initially, when the substrate concentration is increased, the check off rate of reaction increases considerably. However, as the substrate concentration is increased further the essay on a short effects on the reaction rate start to decline, until a stage is reached where increasing the substrate concentration has little further effect on the reaction rate. At this point the enzyme is paper check off considered to be coming close to saturation with substrate, and demonstrating its maximal velocity ( V max ). Note that this maximal velocity is in fact a theoretical limit that will not be truly achieved in any experiment, although we might come very close to it. The relationship described here is is a necessary evil a fairly common one, which a mathematician would immediately identify as a rectangular hyperbola. The equation that describes such a relationship is as follows: The two constants a and b thus allow us to describe this hyperbolic relationship, just as with a linear relationship ( y = mx + c ), which can be expressed by the two constants m (the slope) and c (the intercept).

We have in fact already defined the constant a — it is V max . The constant b is a little more complex, as it is the value on the x -axis that gives half of the maximal value of check y . In enzymology we refer to this as the Michaelis constant ( K m ), which is defined as the substrate concentration that gives half-maximal velocity. Our final equation, usually called the Michaelis–Menten equation, therefore becomes: In 1913, Leonor Michaelis and Maud Menten first showed that it was in fact possible to derive this equation mathematically from first principles, with some simple assumptions about the way in which an enzyme reacts with a substrate to form a product. Central to on declaration their derivation is the concept that the reaction takes place via the formation of an ES complex which, once formed, can either dissociate (productively) to paper release product, or else dissociate in the reverse direction without any formation of product. Writing? Thus the reaction can be represented as follows, with k 1 , k ?1 and k 2 being the rate constants of the three individual reaction steps: The Michaelis–Menten derivation requires two important assumptions. The first assumption is that we are considering the initial velocity of the reaction ( v 0 ), when the product concentration will be negligibly small (i.e. Paper Off? [S] ? [P]), such that we can ignore the possibility of any product reverting to substrate. Essay On Advertising Is A? The second assumption is that the concentration of substrate greatly exceeds the concentration of enzyme (i.e. [S]?[E]). The derivation begins with an paper off, equation for the expression of the initial rate, the rate of resume writing service formation of product, as the rate at which the ES complex dissociates to form product.

This is based upon the rate constant k 2 and the concentration of the ES complex, as follows: 1. Since ES is an intermediate, its concentration is unknown, but we can express it in terms of known values. In a steady-state approximation we can assume that although the paper check concentration of essay on a short story substrate and product changes, the concentration of the ES complex itself remains constant. The rate of formation of the ES complex and paper off, the rate of its breakdown must therefore balance, where: and. Hence, at steady state: This equation can be rearranged to yield [ES] as follows: 2. The Michaelis constant K m can be defined as follows: Equation 2 may thus be simplified to: 3. Since the concentration of substrate greatly exceeds the concentration of enzyme (i.e. [S] ? [E]), the concentration of with uk uncombined substrate [S] is check almost equal to the total concentration of substrate. The concentration of uncombined enzyme [E] is equal to the total enzyme concentration [E] T minus that combined with substrate [ES].

Introducing these terms to Equation 3 and with uk, solving for ES gives us the following: 4. We can then introduce this term into Equation 1 to give: 5. The term k 2 [E] T in fact represents V max , the check maximal velocity. Thus Michaelis and Menten were able to derive their final equation as: A more detailed derivation of the Michaelis–Menten equation can be found in many biochemistry textbooks (see section 4 of Recommended Reading section). There are also some very helpful web-based tutorials available on the subject. Michaelis constants have been determined for many commonly used enzymes, and are typically in writing a critical, the lower millimolar range (Table 5). It should be noted that enzymes which catalyse the same reaction, but which are derived from paper, different organisms, can have widely differing K m values. Furthermore, an enzyme with multiple substrates can have quite different K m values for each substrate.

A low K m value indicates that the enzyme requires only a small amount of substrate in order to become saturated. Therefore the maximum velocity is reached at relatively low substrate concentrations. On Declaration Of Independence? A high K m value indicates the need for high substrate concentrations in order to achieve maximum reaction velocity. Thus we generally refer to K m as a measure of the affinity of the enzyme for its substrate—in fact it is an inverse measure, where a high K m indicates a low affinity, and vice versa. The K m value tells us several important things about a particular enzyme. An enzyme with a low K m value relative to paper check off the physiological concentration of substrate will probably always be saturated with substrate, and writing a critical essay, will therefore act at a constant rate, regardless of variations in the concentration of substrate within the physiological range. An enzyme with a high K m value relative to the physiological concentration of substrate will not be saturated with substrate, and its activity will therefore vary according to the concentration of substrate, so the rate of off formation of product will depend on the availability of substrate. If an 10 best resume writing executives, enzyme acts on several substrates, the substrate with the lowest K m value is frequently assumed to be that enzyme's ‘natural’ substrate, although this may not be true in all cases. If two enzymes (with similar V max ) in different metabolic pathways compete for the same substrate, then if we know the K m values for the two enzymes we can predict the relative activity of the two pathways.

Essentially the pathway that has the enzyme with the lower K m value is likely to be the ‘preferred pathway’, and more substrate will flow through that pathway under most conditions. For example, phosphofructokinase (PFK) is the paper off enzyme that catalyses the first committed step in the glycolytic pathway, which generates energy in the form of ATP for the cell, whereas glucose-1-phosphate uridylyltransferase (GUT) is an enzyme early in the pathway leading to the synthesis of glycogen (an energy storage molecule). Both enzymes use hexose monophosphates as substrates, but the K m of PFK for its substrate is invisible lower than that of check GUT for its substrate. Thus at lower cellular hexose phosphate concentrations, PFK will be active and GUT will be largely inactive. At higher hexose phosphate concentrations both pathways will be active. This means that the cells only essay, store glycogen in times of plenty, and always give preference to the pathway of ATP production, which is the more essential function. Very often it is not possible to estimate K m values from a direct plot of paper velocity against substrate concentration (as shown in Figure 6) because we have not used high enough substrate concentrations to come even close to estimating maximal velocity, and therefore we cannot evaluate half-maximal velocity and on declaration of independence, thus K m . Fortunately, we can plot our experimental data in a slightly different way in order to paper check off obtain these values. The most commonly used alternative is the Lineweaver–Burk plot (often called the double-reciprocal plot). This plot linearizes the hyperbolic curved relationship, and the line produced is easy to extrapolate, allowing evaluation of invisible V max and K m . For example, if we obtained only the first seven data points in paper off, Figure 6, we would have difficulty estimating V max from a direct plot as shown in Figure 7a.

However, as shown in Figure 7b, if these seven points are plotted on a graph of 1/velocity against 1/substrate concentration (i.e. a double-reciprocal plot), the data are linearized, and the line can be easily extrapolated to the left to provide intercepts on both the y -axis and the x -axis, from how to example, which V max and paper off, K m , respectively, can be evaluated. One significant practical drawback of using the help uk Lineweaver–Burk plot is the excessive influence that it gives to measurements made at paper check the lowest substrate concentrations. 10 Best? These concentrations might well be the most prone to error (due to check off difficulties in making multiple dilutions), and result in reaction rates that, because they are slow, might also be most prone to measurement error. Often, as shown in Figure 8, such points when transformed on the Lineweaver–Burk plot have a significant impact on essay on declaration, the line of paper check off best fit estimated from the data, and help assignments, therefore on the extrapolated values of both V max and K m . Paper? The two sets of points shown in Figure 8 are identical except for writing on a short, the single point at the top right, which reflects (because of the plot's double-reciprocal nature) a single point derived from paper check, a very low substrate concentration and a low reaction rate. However, this single point can have an enormous impact on the line of best fit and on advertising necessary, the accompanying estimates of kinetic constants. In fact there are other kinetic plots that can be used, including the Eadie–Hofstee plot, the Hanes plot and the Eisenthal–Cornish-Bowden plot, which are less prone to such problems. However, the off Lineweaver–Burk plot is still the most commonly described kinetic plot in resume writing executives, the majority of enzymology textbooks, and off, thus retains its influence in undergraduate education. Enzymes are affected by pH and writing, temperature. Various environmental factors are able to affect the rate of enzyme-catalysed reactions through reversible or irreversible changes in the protein structure. The effects of pH and temperature are generally well understood.

Most enzymes have a characteristic optimum pH at which the velocity of the catalysed reaction is maximal, and above and below which the velocity declines (Figure 9). The pH profile is dependent on paper, a number of factors. As the pH changes, the how to a interview ionization of groups both at the enzyme's active site and on the substrate can alter, influencing the rate of binding of the substrate to the active site. These effects are often reversible. Paper? For example, if we take an enzyme with an optimal pH (pH opt ) of 7.0 and place it in an environment at pH 6.0 or 8.0, the charge properties of the enzyme and the substrate may be suboptimal, such that binding and hence the reaction rate are lowered. Help Uk? If we then readjust the pH to 7.0, the optimal charge properties and hence the maximal activity of the enzyme are often restored. However, if we place the enzyme in a more extreme acidic or alkaline environment (e.g. at pH 1 or 14), although these conditions may not actually lead to changes in the very stable covalent structure of the protein (i.e. Off? its configuration), they may well produce changes in writing service executives, the conformation (shape) of the protein such that, when it is returned to pH 7.0, the paper check original conformation and essay on advertising is a necessary, hence the enzyme's full catalytic activity are not restored. It should be noted that the optimum pH of an enzyme may not be identical to that of its normal intracellular surroundings. This indicates that the paper check local pH can exert a controlling influence on enzyme activity. The effects of temperature on writing short, enzyme activity are quite complex, and can be regarded as two forces acting simultaneously but in paper check off, opposite directions. As the temperature is essay on a raised, the rate of molecular movement and hence the rate of reaction increases, but at the same time there is a progressive inactivation caused by denaturation of the enzyme protein.

This becomes more pronounced as the temperature increases, so that an apparent temperature optimum (T opt ) is observed (Figure 10). Thermal denaturation is time dependent, and for check off, an enzyme the term ‘optimum temperature’ has little real meaning unless the duration of exposure to that temperature is recorded. The thermal stability of an enzyme can be determined by first exposing the protein to a range of temperatures for write a interview report example, a fixed period of time, and paper check off, subsequently measuring its activity at one favourable temperature (e.g. 25°C). The temperature at with assignments which denaturation becomes important varies from one enzyme to another. Check? Normally it is negligible below 30°C, and starts to become appreciable above 40°C. Typically, enzymes derived from microbial sources show much higher thermal stability than do those from mammalian sources, and enzymes derived from extremely thermophilic microorganisms, such as thermolysin (a protease from Bacillus thermoproteolyticus ) and Taq polymerase (a DNA polymerase from write, Thermus aquaticus ), might be completely thermostable at 70°C and still retain substantial levels of activity even at 100°C. Enzymes are sensitive to inhibitors. Substances that reduce the activity of an enzyme-catalysed reaction are known as inhibitors.

They act by either directly or indirectly influencing the catalytic properties of the active site. Inhibitors can be foreign to the cell or natural components of it. Those in the latter category can represent an paper check, important element of the 10 best service regulation of cell metabolism. Off? Many toxins and also many pharmacologically active agents (both illegal drugs and resume, prescription and over-the-counter medicines) act by inhibiting specific enzyme-catalysed processes. Inhibitors are classified as reversible inhibitors when they bind reversibly to paper an enzyme. A molecule that is structurally similar to the normal substrate may be able to bind reversibly to the enzyme's active site and therefore act as a competitive inhibitor.

For example, malonate is a competitive inhibitor of the enzyme succinate dehydrogenase, as it is a critical on a short story capable of paper binding to the enzyme's active site due to its close structural similarity to the enzyme's natural substrate, succinate (see below). When malonate occupies the active site of succinate dehydrogenase it prevents the natural substrate, succinate, from essay on advertising is a necessary, binding, thereby slowing down the rate of oxidation of succinate to fumarate (i.e. inhibiting the reaction). One of the characteristics of check competitive inhibitors is that they can be displaced from the active site if high concentrations of substrate are used, thereby restoring enzyme activity. Thus competitive inhibitors increase the K m of with a reaction because they increase the concentration of substrate required to saturate the enzyme. However, they do not change V max itself.

In the case of certain enzymes, high concentrations of either the substrate or the off product can be inhibitory. For example, invertase activity is considerably reduced in 10 best service executives, the presence of high concentrations of check sucrose (its substrate), whereas the how to a interview report example ?-galactosidase of off Aspergillus niger is strongly inhibited by galactose (its product). Products of an enzyme reaction are some of the most commonly encountered competitive inhibitors. Other types of reversible inhibitor also exist. Non-competitive inhibitors react with the enzyme at a site distinct from the active site. Therefore the binding of the inhibitor does not physically block the substrate–binding site, but it does prevent subsequent reaction. Most non-competitive inhibitors are chemically unrelated to the substrate, and is a evil, their inhibition cannot be overcome by increasing the substrate concentration. Paper Check Off? Such inhibitors in effect reduce the concentration of the active enzyme in solution, thereby reducing the V max of the service executives reaction. Paper Off? However, they do not change the value of K m . Uncompetitive inhibition is rather rare, occurring when the inhibitor is only able to bind to the enzyme once a substrate molecule has itself bound. How To Write Report Example? As such, inhibition is most significant at high substrate concentrations, and results in a reduction in paper, the V max of the reaction. Uncompetitive inhibition also causes a reduction in K m , which seems somewhat counterintuitive as this means that the affinity of the enzyme for its substrate is actually increased when the inhibitor is present.

This effect occurs because the binding of the inhibitor to the ES complex effectively removes ES complex and thereby affects the help assignments overall equilibrium of the paper check reaction favouring ES complex formation. Argumentative Essay On Declaration Of Independence? It is noteworthy however that since both V max and K m are reduced the observed reaction rates with inhibitor present are always lower than those in the absence of the uncompetitive inhibitor. Irreversible inhibitors and poisons. If an inhibitor binds permanently to paper check an enzyme it is known as an irreversible inhibitor. Many irreversible inhibitors are therefore potent toxins. Organophosphorus compounds such as diisopropyl fluorophosphate (DFP) inhibit acetylcholinesterase activity by reacting covalently with an important serine residue found within the active site of the enzyme. The physiological effect of argumentative essay of independence this inactivation is interference with neurotransmitter inactivation at the synapses of nerves, resulting in check off, the constant propagation of nerve impulses, which can lead to invisible death.

DFP was originally evaluated by off, the British as a chemical warfare agent during World War Two, and modified versions of this compound are now widely used as organophosphate pesticides (e.g. parathione, malathione). Allosteric regulators and the control of enzyme activity. Having spent time learning about enzyme kinetics and the Michaelis–Menten relationship, it is often quite disconcerting to find that some of the most important enzymes do not in fact display such properties. Allosteric enzymes are key regulatory enzymes that control the assignments activities of metabolic pathways by responding to inhibitors and activators. These enzymes in fact show a sigmoidal (S-shaped) relationship between reaction rate and substrate concentration (Figure 11), rather than the usual hyperbolic relationship. Thus for allosteric enzymes there is an area where activity is lower than that of an paper off, equivalent ‘normal’ enzyme, and help with uk, also an area where activity is higher than that of an equivalent ‘normal’ enzyme, with a rapid transition between these two phases. Check Off? This is rather like a switch that can quickly be changed from ‘off’ (low activity) to ‘on’ (full activity). Most allosteric enzymes are polymeric—that is, they are composed of at least two (and often many more) individual polypeptide chains. They also have multiple active sites where the substrate can bind. Much of our understanding of the function of allosteric enzymes comes from 10 best, studies of haemoglobin which, although it is not an enzyme, binds oxygen in a similarly co-operative way and check off, thus also demonstrates this sigmoidal relationship. Allosteric enzymes have an initially low affinity for the substrate, but when a single substrate molecule binds, this may break some bonds within the enzyme and thereby change the shape of the invisible resume protein such that the remaining active sites are able to bind with a higher affinity.

Therefore allosteric enzymes are often described as moving from a tensed state or T-state (low affinity) in which no substrate is bound, to a relaxed state or R-state (high affinity) as substrate binds. Other molecules can also bind to allosteric enzymes, at paper off additional regulatory sites (i.e. Essay On Declaration? not at the active site). Molecules that stabilize the protein in its T-state therefore act as allosteric inhibitors, whereas molecules that move the protein to paper off its R-state will act as allosteric activators or promoters. A good example of an allosteric enzyme is aspartate transcarbamoylase (ATCase), a key regulatory enzyme that catalyses the on a story first committed step in the sequence of reactions that produce the pyrimidine nucleotides which are essential components of DNA and RNA. Paper Off? The reaction is as follows: The end product in the pathway, the pyrimidine nucleotide cytidine triphosphate (CTP), is an active allosteric inhibitor of the enzyme ATCase. Therefore when there is a high concentration of CTP in the cell, this feeds back and inhibits the ATCase enzyme, reducing its activity and thus lowering the rate of production of further pyrimidine nucleotides.

As the on declaration of independence concentration of CTP in the cell decreases then so does the inhibition of ATCase, and the resulting increase in enzyme activity leads to the production of paper more pyrimidine nucleotides. This negative feedback inhibition is an important element of biochemical homeostasis within the cell. However, in order to synthesize DNA and RNA, the cell requires not only pyrimidine nucleotides but also purine nucleotides, and these are needed in roughly equal proportions. Purine synthesis occurs through a different pathway, but interestingly the final product, the necessary purine nucleotide adenosine triphosphate (ATP), is a potent activator of the paper check enzyme ATCase. This is logical, since when the cell contains high concentrations of purine nucleotides it will require equally high concentrations of pyrimidine nucleotides in order for these two types of nucleotide to combine to form the polymers DNA and RNA. Thus ATCase is able to regulate the production of pyrimidine nucleotides within the cell according to cellular demand, and also to invisible ensure that pyrimidine nucleotide synthesis is off synchronized with purine nucleotide synthesis—an elegant biochemical mechanism for the regulation of an extremely important metabolic process.

There are some rare, although important, cases of monomeric enzymes that have only one substrate-binding site but are capable of demonstrating the sigmoidal reaction kinetics characteristic of allosteric enzymes. Writing A Critical? Particularly noteworthy in this context is the off monomeric enzyme glucokinase (also called hexokinase IV), which catalyses the invisible resume phosphorylation of glucose to glucose-6-phosphate (which may then either be metabolized by the glycolytic pathway or be used in glycogen synthesis). It has been postulated that this kinetic behaviour is a result of paper check individual glucokinase molecules existing in one of two forms—a low-affinity form and a high-affinity form. The low-affinity form of the enzyme reacts with its substrate (glucose), is then turned into the high-affinity form, and remains in that state for a short time before slowly returning to its original low-affinity form (demonstrating a so-called slow transition). Therefore at high substrate concentrations the enzyme is likely to react with a second substrate molecule soon after the first one (i.e. while still in its high-affinity form), whereas at lower substrate concentrations the enzyme may transition back to its low-affinity form before it reacts with subsequent substrate molecules. Essay Necessary Evil? This results in its characteristic sigmoidal reaction kinetics. Origin, purification and uses of enzymes. Enzymes are essential components of animals, plants and microorganisms, due to the fact that they catalyse and co-ordinate the complex reactions of cellular metabolism.

Up until the 1970s, most of the commercial application of enzymes involved animal and plant sources. Paper Off? At that time, bulk enzymes were generally only how to write, used within the food-processing industry, and enzymes from animals and plants were preferred, as they were considered to paper off be free from the problems of resume executives toxicity and contamination that were associated with enzymes of microbial origin. However, as demand grew and as fermentation technology developed, the competitive cost of microbial enzymes was recognized and they became more widely used. Compared with enzymes from plant and animal sources, microbial enzymes have economic, technical and ethical advantages, which will now be outlined. The sheer quantity of paper off enzyme that can be produced within a short time, and in a small production facility, greatly favours the on a use of microorganisms. For example, during the production of rennin (a milk-coagulating enzyme used in cheese manufacture) the traditional approach is to use the enzyme extracted from the stomach of a calf (a young cow still feeding on its mother's milk). The average quantity of rennet extracted from a calf's stomach is 10 kg, and it takes several months of intensive farming to produce a calf. Paper Check Off? In comparison, a 1 000-litre fermenter of recombinant Bacillus subtilis can produce 20 kg of enzyme within 12 h. Thus the microbial product is clearly preferable economically, and is free from the ethical issues that surround the use of animals. Indeed, most of the cheese now sold in essay, supermarkets is made from milk coagulated with microbial enzymes (so is suitable for vegetarians).

A further advantage of using microbial enzymes is their ease of extraction. Many of the microbial enzymes used in biotechnological processes are secreted extracellularly, which greatly simplifies their extraction and purification. Paper Check? Microbial intracellular enzymes are also often easier to obtain than the equivalent animal or plant enzymes, as they generally require fewer extraction and purification steps. Animal and plant sources usually need to be transported to the extraction facility, whereas when microorganisms are used the same facility can generally be employed for production and extraction. In addition, commercially important animal and plant enzymes are often located within only one organ or tissue, so the remaining material is essentially a waste product, disposal of which is required.

Finally, enzymes from plant and animal sources show wide variation in yield, and may only invisible, be available at certain times of year, whereas none of these problems are associated with microbial enzymes. Microbial enzymes often have properties that make them more suitable for commercial exploitation. In comparison with enzymes from paper check, animal and of independence, plant sources, the stability of microbial enzymes is usually high. For example, the high temperature stability of enzymes from check off, thermophilic microorganisms is often useful when the process must operate at high temperatures (e.g. during starch processing). Microorganisms are also very amenable to genetic modification to produce novel or altered enzymes, using relatively simple methods such as plasmid insertion.

The genetic manipulation of animals and plants is technically much more difficult, is essay on declaration of independence more expensive and is still the subject of paper check off significant ethical concern, especially in the U.K. Enzymes may be intracellular or extracellular. Although many enzymes are retained within the resume cell, and may be located in off, specific subcellular compartments, others are released into the surrounding environment. The majority of enzymes in resume writing service executives, industrial use are extracellular proteins from either fungal sources (e.g. Aspergillus species) or bacterial sources (e.g.

Bacillus species). Examples of these include ?-amylase, cellulase, dextranase, proteases and paper off, amyloglucosidase. Many other enzymes for non-industrial use are intracellular and are produced in resume writing executives, much smaller amounts by the cell. Examples of these include asparaginase, catalase, cholesterol oxidase, glucose oxidase and glucose-6-phosphate dehydrogenase. Within the cell, enzymes are generally found along with other proteins, nucleic acids, polysaccharides and lipids. Paper Check? The activity of the enzyme in write report example, relation to the total protein present (i.e. the specific activity) can be determined and used as a measure of enzyme purity. A variety of methods can be used to remove contaminating material in order to purify the check enzyme and increase its specific activity. Enzymes that are used as diagnostic reagents and in clinical therapeutics are normally prepared to a high degree of purity, because great emphasis is placed on the specificity of the reaction that is being catalysed. Clearly the help assignments uk higher the level of purification, the greater the cost of paper check enzyme production. In the case of many bulk industrial enzymes the degree of purification is less important, and such enzymes may often be sold as very crude preparations of culture broth containing the with assignments growth medium, organisms (whole or fragmented) and enzymes of paper interest.

However, even when the cheapest bulk enzymes are utilized (e.g. proteases for use in help uk, washing powders), the enzyme cost can contribute around 5–10% of the final product value. At the end of a fermentation in which a microorganism rich in the required enzyme has been cultured, the broth may be cooled rapidly to paper check off 5°C to prevent further microbial growth and stabilize the enzyme product. The pH may also be adjusted to optimize enzyme stability. If the enzyme-producing organism is a fungus, this may be removed by how to write a interview example, centrifugation at low speed. If the enzyme source is bacterial, the bacteria are often flocculated with aluminum sulfate or calcium chloride, which negate the charge on the bacterial membranes, causing them to clump and thus come out of suspension. Extracellular enzymes are found in the liquid component of the pretreatment process. However, intracellular enzymes require more extensive treatment. The biomass may be concentrated by centrifugation and washed to remove medium components.

The cellular component must then be ruptured to release the enzyme content. This can be done using one or more of the following processes: • ball milling (using glass beads) • enzymic removal of the cell wall. • liquid shearing through a small orifice at high pressure (e.g. Paper Check? within a French press) Separation of enzymes from the resulting solution may then involve a variety of separation processes, which are often employed in essay is a necessary evil, a sequential fashion. The first step in an enzyme purification procedure commonly involves separation of the proteins from the non-protein components by paper check off, a process of salting out. On A Short? Proteins remain in aqueous solution because of interactions between the hydrophilic (water-loving) amino acids and paper check, the surrounding water molecules (the solvent). Help With Assignments Uk? If the paper off ionic strength of the solvent is increased by adding an agent such as ammonium sulfate, some of the water molecules will interact with the salt ions, thereby decreasing the number of water molecules available to interact with the protein.

Under such conditions, when protein molecules cannot interact with the solvent, they interact with each other, coagulating and coming out of solution in the form of a precipitate. This precipitate (containing the enzyme of how to write report example interest and other proteins) can then be filtered or centrifuged, and separated from the supernatant. Since different proteins vary in the extent to which they interact with water, it is possible to perform this process using a series of additions of ammonium sulfate, increasing the ionic strength in a stepwise fashion and removing the paper check precipitate at each stage. Essay On Declaration Of Independence? Thus such fractional precipitation is off not only capable of separating protein from non-protein components, but can also enable separation of the enzyme of interest from some of the other protein components. Subsequently a wide variety of techniques may be used for resume, further purification, and steps involving chromatography are standard practice. Ion-exchange chromatography is often effective during the early stages of the purification process. The protein solution is paper added to a column containing an insoluble polymer (e.g. cellulose) that has been modified so that its ionic characteristics will determine the type of mobile ion (i.e. cation or anion) it attracts.

Proteins whose net charge is opposite to that of the ion-exchange material will bind to it, whereas all other proteins will pass through the column. A subsequent change in pH or the uk introduction of off a salt solution will alter the electrostatic forces, allowing the retained protein to be released into solution again. Gel filtration can be utilized in the later stages of a purification protocol to essay on a story separate molecules on the basis of molecular size. Columns containing a bed of cross-linked gel particles such as Sephadex are used. These gel particles exclude large protein molecules while allowing the entry of smaller molecules. Separation occurs because the larger protein molecules follow a path down the column between the Sephadex particles (occupying a smaller fraction of the column volume). Larger molecules therefore have a shorter elution time and are recovered first from the paper gel filtration column. Affinity chromatography procedures can often enable purification protocols to be substantially simplified.

Typically, with respect to enzyme purification, a column would be packed with a particulate stationary phase to which a ligand molecule such as a substrate analogue, inhibitor or cofactor of the enzyme of interest would be firmly bound. As the sample mixture is is a passed through the column, the enzyme interacts with, and binds, to the immobilised ligand, being retained within the column as all of the other components of the mixture pass through the column unrewarded. Subsequently a solution of the ligand is introduced to the column to release (elute) and thereby recover the bound enzyme from the column in a highly purified form. Nowadays numerous alternative affinity chromatography procedures exist that are able to separate enzymes by paper off, binding to argumentative essay areas of the molecule away form their active site. Advances in molecular biology enable us to purify recombinant proteins, including enzymes, through affinity tagging. In a typical approach the gene for the enzyme of interest would be modified to code for a further short amino acid sequence at either the N- or C- terminal. For example, a range of polyhistidine tagging procedures are available to yield protein products with six or more consecutive histidine residues at their N- or C- terminal end. When a mixture containing the tagged protein of check off interest is subsequently passed through a column containing a nickel-nitrilotriacetic acid (Ni-NTA) agarose resin, the writing executives histidine residues on the recombinant protein bind to the nickel ions attached to the support resin, retaining the protein, whilst other protein and non-protein components pass through the check column. Elution of the essay bound protein can then be accomplished by check off, adding imidazole to the column, or by reducing the pH to 5-6 to displace the His-tagged protein from the nickel ions. Such techniques are therefore capable of rapidly and highly effectively isolating an enzyme from a complex mixture in only one step, and typically provide protein purities of up to essay evil 95%. If more highly purified enzyme products are required, other supplemental options are also available, including various forms of preparative electrophoresis e.g. Check? disc-gel electrophoresis and isoelectric focusing.

Enzymes are antigenic, and since problems occurred in the late 1960s when manufacturing workers exhibited severe allergic responses after breathing enzyme dusts, procedures have now been implemented to reduce dust formation. These involve supplying enzymes as liquids wherever possible, or increasing the particle size of dry powders from 10 ?m to 200–500 ?m by either prilling (mixing the argumentative on declaration enzyme with polyethylene glycol and preparing small spheres by atomization) or marumerizing (mixing the enzyme with a binder and water, extruding long filaments, converting them into spheres in a marumerizer, drying them and paper off, covering them with a waxy coat). Although many industrial processes, such as cheese manufacturing, have traditionally used impure enzyme sources, often from animals or plants, the development of much of modern industrial enzymology has gone hand in hand with the how to a interview report example commercial exploitation of microbial enzymes. These were introduced to off the West in around 1890 when the Japanese scientist Jokichi Takamine settled in the U.S.A. and argumentative, set up an enzyme factory based on Japanese technology. The principal product was Takadiastase, a mixture of amylolytic and proteolytic enzymes prepared by cultivating the fungus Aspergillus oryzae on rice or wheat bran. Takadiastase was marketed successfully in paper check, the U.S.A. as a digestive aid for the treatment of resume executives dyspepsia, which was then believed to result from the paper check off incomplete digestion of starch. Bacterial enzymes were developed in France by August Boidin and Jean Effront, who in 1913 found that Bacillus subtilis produced a heat-stable ?-amylase when grown in a liquid medium made by resume executives, extraction of malt or grain. The enzyme was primarily used within the textile industry for the removal of the starch that protects the warp in the manufacture of cotton.

In around 1930 it was found that fungal pectinases could be used in the preparation of fruit products. In subsequent years, several other hydrolases were developed and sold commercially (e.g. pectosanase, cellulase, lipase), but the technology was still fairly rudimentary. After World War Two the fermentation industry underwent rapid development as methods for the production of antibiotics were developed. These methods were soon adapted for the production of enzymes. In the 1960s, glucoamylase was introduced as a means of hydrolysing starch, replacing acid hydrolysis. Subsequently, in the 1960s and 1970s, proteases were incorporated into detergents and then glucose isomerase was introduced to produce sweetening agents in the form of high-fructose syrups.

Since the 1990s, lipases have been incorporated into washing powders, and a variety of immobilized enzyme processes have been developed (see section on enzyme immobilization), many of which utilize intracellular enzymes. Currently, enzymes are used in four distinct fields of commerce and technology (Table 6): • as industrial catalysts. • as therapeutic agents. • as analytic reagents. • as manipulative tools (e.g. in genetics). Of the thousands of different types of enzymes, about 95% are available from suppliers in quantities ranging from ?g to kg, provided essentially for research purposes. Around 40–50 enzymes are produced on an industrial scale (i.e. ranging from multiple kilograms to paper check tonnes per annum).

The global enzyme market is currently dominated by resume service, the hydrolases, especially the proteases, together with amylases, cellulases and lipases supplied either as liquid concentrates or as powders or granules that release the soluble enzyme on off, dissolution. Global production is dominated by two companies, which between them supply more than two-thirds of the global enzyme market, namely the Danish company Novozymes, with a market share of 47%, and the U.S. company DuPont (which recently acquired Genencor), with 21%. The value of the world enzyme market has increased steadily from resume, ?110 million in 1960 to check off ?200 million in invisible, 1970, ?270 million in 1980, ?1 000 million in off, 1990 and over ?2 000 million in resume, 2010. Food and beverage enzymes represented the largest sector of the paper industrial enzymes market in 2010, with a value of ?750 million, and write, the market for enzymes for check off, technical applications (including diagnostic applications, research and biotechnology) accounted for a further ?700 million. Estimates of future demand are in the range of argumentative essay on declaration ?4 000–5 000 million between 2015 and off, 2016, growing at how to a interview report a rate of 6–7% annually. The developing economies of the Asia-Pacific Region, the Middle East and paper off, Africa are now seen to be emerging as the how to write a interview example fastest growing markets for industrial enzymes. Microbial enzymes are typically produced in batches by culturing the producing organism within a batch fermenter. Fermentation typically lasts between 30 and paper, 150 h, with the on advertising evil optimum enzyme yield for the process falling somewhere between the optimum biomass yield and the point of maximal enzyme activity within the cells. Check Off? Relatively small fermenters with a volume of how to example 10–100 m 3 are generally employed, allowing flexibility where a number of different products are being produced.

Many production systems are optimized by means of a fed-batch process, in which substrates are gradually fed into the reactor over paper the course of the fermentation, rather than being provided all at once at the start of the process. True continuous culture techniques have been used in laboratory-scale studies, but have not been widely implemented on a commercial scale, although Novozymes does have a continuous process for the production of glucose isomerase, since this is a larger-volume market and the company has a very strong market share. During the help assignments production of commercially important products via enzymatic catalysis, soluble enzymes have traditionally been used in paper check off, batch processes that employ some form of stirred-tank reactor (STR). In these processes, at the end of the batch run the product must be separated from any unused substrate, and also from the enzyme catalyst. Removal of the enzyme at this stage can be achieved by thermal denaturation (only if the product is write a interview report example thermostable) or by ammonium sulfate precipitation or ultrafiltration. These processes represent a costly downstream processing stage and generally render the enzyme inactive, so when a new batch run is to be started a fresh batch of enzyme is required. Immobilized enzyme systems, in contrast, ‘fix’ the enzyme so that it can be reused many times, which has a significant impact on production costs. Paper Check? As a very simple example, if an enzyme is mixed with a solution of warm (but not too hot) agar and this is allowed to set, the enzyme will be entrapped (for the purposes of this example let us ignore the fact that the enzyme will gradually leak out of this gel). The agar can then be cut up into invisible cubes and these can be placed in a STR, together with substrate, as shown in Figure 12. Again the reaction would be allowed to proceed (and it might actually be slower due to diffusional constraints and other effects described later).

At the end of the batch run the catalyst can now be easily separated from the product by passing the paper check reactor contents through a coarse mesh. Immediately an important downstream processing step has been carried out and, just as importantly, the active enzyme has been recovered so that it can be reused for the next batch run. On Declaration Of Independence? This ease of paper check separation of enzyme from a critical short story, product is paper check a major advantage of all immobilized systems over invisible resume their counterparts that use free (i.e. soluble) enzyme. This physical advantage of paper ease of how to write example reuse of immobilized biocatalysts is one of the main reasons why such systems are favoured commercially. Check? However, immobilization may also produce biochemical changes that lead to enhanced biocatalyst stability, which may be manifested as: • an write, increased rate of catalysis.

• prolonged duration of catalysis. • greater operational stability to extremes of pH, temperature, etc. The particular advantage(s) conferred by immobilization will therefore differ from one system to another. Paper Off? It should be noted that often there may be no biochemical advantage at resume all, and the simple physical advantage of ease of separation of the biocatalyst from the product may be sufficient to favour the commercial development of an immobilized process. At this point one problem that will immediately spring to mind for most students is paper off that they have always been taught to fully mix all of the reagents of a reaction, yet the basic principle of resume immobilization is to partition the biocatalyst into a distinct phase, rather than mix it homogeneously with the substrate. Will this not cause reaction rates to be low? The answer to this question is yes, and the relationship between the activity of an immobilized system and a non-immobilized system can be expressed as the effectiveness factor (?), where: Thus an immobilized system with an effectiveness factor of 0.1 would show only 10% of the activity of a non-immobilized system with the same amount of enzyme and operating under the same conditions. At first sight this might appear to be a major problem. Check Off? However, if it is possible to reuse the biocatalyst many times this is still economically viable, even with systems that have a low effectiveness factor.

In principle, therefore, for economic viability: Thus if an immobilized system has an effectiveness factor of 0.1 (i.e. 10%) and we can reuse the biocatalyst 10 times, we essentially achieve the 10 best same overall catalytic activity with both the non-immobilized system and off, the immobilized one. However, if we are able to reuse the biocatalyst 100 times we in fact obtain 10 times more total activity from the immobilized system than from the equivalent non-immobilized system, so the immobilized system may be economically preferable. Once a biocatalyst has been immobilized it can also be put in a range of continuous-flow reactors, enabling a continuous supply of substrate to be turned into product as it passes through the reactor. The control of such continuous-flow reactors can be highly automated, leading to considerable savings in production costs. For example, a STR can be easily modified to produce a continuous-flow stirred-tank reactor (CSTR) (Figure 13a), in which the enzyme is held within the assignments reactor by a coarse mesh, and check, the product continuously flows out of the reactor as substrate is pumped in. It is also possible to produce a packed-bed reactor (PBR) (Figure 13b), in which the agar cubes are packed into a column and the substrate is pumped through the bed without any need for stirring. CSTRs and writing service, PBRs enable the enzyme to paper be reused many times before it needs to help with assignments uk be replaced. Check Off? For example, in the production of high-fructose syrups, the immobilized glucose isomerase enzyme would typically be used continuously for between 2 and 4 months, and only after this time (when its activity would have dropped to how to a interview report 25% of the original level) would it need to be replaced. The overall operating costs of continuous-flow reactors are often significantly lower than those of paper off equivalent batch processes.

Batch reactors need to be emptied and refilled frequently at regular intervals. Not only is 10 best writing this procedure expensive, but it also means that there are considerable periods of time when such reactors are not productive (so-called ‘downtime’). Paper Check Off? In addition, batch processes make uneven demands on both labour and services. They may also result in pronounced batch-to-batch variations, as the reaction conditions change with time, and argumentative essay on declaration, they may be difficult to scale up, due to the changing power requirements for paper check, efficient mixing. Due to their higher overall process efficiency, continuous processes using immobilized enzymes may be undertaken in production facilities that are around 10 to 100 times smaller than those required for equivalent batch processes using soluble enzymes. Therefore the capital costs involved in resume writing service, setting up the paper check off facility are also considerably lower. It should be noted that although the help assignments uk agar entrapment method described here has provided a useful example, it is not a particularly effective form of immobilization. Paper Check? The high temperature required to prevent the agar from setting may lead to thermal inactivation of the enzyme, and essay of independence, the agar gel itself is very porous and will allow the enzyme to leak out into the surrounding solution. There are in paper check, fact thousands of different techniques of immobilization, all of which are much more effective than our example.

In general these techniques can be classified as belonging to one of three categories (Figure 14): The physical adsorption of an a critical essay short story, enzyme to check off a supporting matrix is the oldest method of immobilization. As early as 1916, J.M. Nelson and Edward G. Griffin described the adsorption of service yeast invertase on paper off, to activated charcoal, and the subsequent use of this preparation for sucrose hydrolysis. Over the invisible resume years a variety of adsorbents have been used, including cellulose, Sephadex, polystyrene, kaolinite, collagen, alumina, silica gel and glass.

Such immobilization procedures are extremely easy to perform, as the adsorbent and enzyme are simply stirred together for off, a time (typically minutes to hours). Necessary? The binding forces that immobilize the catalyst on the support may involve hydrogen bonds, van der Waals forces, ionic interactions or hydrophobic interactions. Paper Check Off? Such forces are generally weak in comparison with covalent bonds—for example, a hydrogen bond has an energy content of how to about 20 kJ mol ?1 , compared with 200–500 kJ mol ?1 for a covalent bond. Thus, when using such methods, yields (i.e. the amount of enzyme bound per unit of adsorbent) are generally low. Check Off? In addition, adsorption is generally easily reversed, and can lead to desorption of the enzyme at a critical time.

However, despite these limitations, such a method was used in the first commercial immobilized enzyme application, namely DEAE–Sephadex-immobilized l -amino acid acylase, in 1969. DEAE–Sephadex is an ion-exchange resin that consists of an inert dextran particle activated by the addition of writing a critical on a short story numerous diethylaminoethyl groups. Particles of this material remain positively charged at pH 6–8 (see Figure 15a) and thus bind strongly to proteins, which are generally negatively charged in this pH range. If the pH is kept constant, the enzyme and support will remain ionically linked. However, when over time the enzyme loses its activity through denaturation, the pH can be adjusted to a more acidic value, the old enzyme will be desorbed, and the pH can then be readjusted back to pH 6–8 and a fresh batch of enzyme bound. Thus the support matrix may be used many times, giving the process significant economic benefits. Clearly DEAE–Sephadex immobilization is only of value for enzymes that have a neutral-to-alkaline pH optimum. For enzymes that function best under acidic conditions, CM–Sephadex is more suitable.

This contains carboxymethyl groups that remain negatively charged at pH 3.5–4.5 (Figure 15b). Proteins at this pH are generally positively charged and check off, will thus ionically bind to the support. Desorption of the enzyme will occur when the resume pH is adjusted to paper check a more alkaline value. Due to a critical essay short the simplicity and controllability of this immobilization procedure, combined with the economic benefits of paper check off reuse of the support, ion-exchange materials are now widely used as the method of choice in many industrial settings. Immobilization of enzymes by covalent bonding to necessary activated polymers is a widely used approach since, although it is often a tedious procedure, it is capable of producing an immobilized enzyme that is firmly bound to its support. The range of off polymers and chemical coupling procedures that are used is write a interview enormous. The history of covalent bonding for enzyme immobilization dates back to 1949, when F. Paper Check Off? Michael and J. Ewers used the azide derivative of carboxymethylcellulose to immobilize a variety of proteins. Activated cellulose supports continue to be popular due to their inherent advantages of high hydrophilicity, ready availability, potential for derivatization, and the ease with which cellulose-based polymers can be produced either as particulate powders or as membranous films.

It is often more effective not to build the reactive group into the cellulose itself, but instead to use a chemical ‘bridge’ between the cellulose and the enzyme molecule. The requirements for such a bridging or linking molecule are that it must be small, and that once it has reacted with the support it must have a further reactive group capable of necessary reacting with the enzyme. An example of such a bridging molecule is glutaraldehyde, which contains two aldehyde groups, one at check off either end of its (CH 2 ) 3 moiety. At neutral pH values the aldehyde groups will react with free amino groups. Thus one end of the glutaraldehyde molecule may be attached to the support, and the other to the enzyme. Covalently immobilized enzymes are strongly bound to their support, so when the proteins denature they are difficult to remove (in contrast to adsorption, as described earlier). Therefore it is usual for both the enzyme and the support to be replaced. This may result in higher operational costs compared with adsorption techniques in which the support may be reused.

The entrapment of an enzyme can be achieved in a number of ways: • inclusion within the matrix of a highly cross-linked polymer. • separation from the bulk phase by a semi-permeable ‘microcapsule’ • dissolution in a distinct non-aqueous phase. An important feature of entrapment techniques is that the enzyme is not in fact attached to anything. Consequently there are none of the essay on advertising is a steric problems associated with covalent or adsorption methods (i.e. the possibility of the enzyme binding in such a way that its active site is obstructed by part of the supporting polymer matrix). The example of an enzyme retained in paper, agar, described earlier, is a useful illustration of entrapment. A preferable alternative involves mixing the essay on declaration catalyst with sodium alginate gel and extruding this into a solution of calcium chloride to produce solid calcium alginate particles. This technique has the advantage of not requiring the use of high temperatures. However, although it is a popular activity in teaching laboratories, outside that setting it is generally unsuitable for the immobilization of purified enzymes, as these are often able to leak out of the gel. Entrapment techniques for purified enzymes are more likely to involve retaining the enzyme behind some form of check off ultrafiltration membrane. However, gel entrapment procedures may be useful when dealing with larger catalysts, such as whole cells.

For example, gel-immobilized living yeast cells have been used successfully in the manufacture of champagne by on advertising, Moet Chandon. Immobilization: changes in enzyme properties. Earlier in this essay it was suggested that immobilization might change the properties of an enzyme to enhance its stability. Initially it was believed that such enhanced stability resulted from the paper check formation of how to write bonds between the enzyme and the supporting matrix that physically stabilize the structure of the protein. Indeed there are some published reports that describe this phenomenon.

With regard to the stabilization of proteolytic enzymes, which often exhibit more prolonged activity in the immobilized state, this is most probably explained by the fact that such proteases in free solution are prone to autodigestion (i.e. enzyme molecules cleave the peptide bonds of adjacent enzyme molecules), a process that is largely prevented when they are fixed to a supporting matrix. However, the check effects of immobilization are more often due to the supporting matrix changing the is a necessary evil microenvironment around the enzyme and/or introducing diffusional constraints that modify the activity of the catalyst. Paper Off? Consider, for is a necessary, example, immobilization of the check off enzyme by adsorption on to a polyanionic (negatively charged) support such as cellulose. If the substrate is a cation (i.e. positively charged), it will be attracted to the support and thus to the enzyme. In this case the enzyme might well display higher activity, as the substrate concentration in its microenvironment would be higher than that in report example, the surrounding bulk phase. Other cations would also be attracted, and paper, importantly these would include H + ions. Thus the microenvironment would also be enriched in invisible, H + ions, so the pH surrounding the paper off enzyme would be lower than the pH of the bulk phase. Consequently the enzyme would also exhibit an altered pH profile compared with that of its soluble counterpart. In addition, the immobilization matrix might act as a barrier to the diffusion of substrates, products and how to write a interview report example, other molecules.

For example, if a high enzyme loading was put into a gel particle and this was then immersed in substrate solution, the substrate would diffuse into the gel and rapidly be converted into product. Enzyme molecules entrapped deeper within the gel particle might therefore be inactive simply because they had not received any substrate to work on (i.e. all of the substrate was converted to product in the outer layers of the particle). Check Off? Although this is obviously somewhat inefficient, it does have one useful effect. When over time the enzyme within the system denatures, the loss of activity of the enzyme in the outer part of the particle means that substrate will now diffuse deeper into the particle to reach the previously unused core enzyme molecules. In effect this inner reserve of 10 best executives enzyme will offset the check loss of enzyme activity through denaturation, so the system will show little or no overall loss of activity.

This explains the observation that immobilized systems often have a longer operational lifetime than their soluble equivalents. In addition, it is of interest that enzymes bound to natural cell membranes (phospholipid bilayers) within living cells will also probably demonstrate these effects, and immobilized systems thus provide useful models for write a interview report, the study of such membrane-bound proteins in living cells. The major industrial processes that utilize immobilized enzymes are listed in off, Table 7. Sales of immobilized enzymes peaked in 10 best resume writing, 1990, when they accounted for about 20% of all industrial enzyme sales, almost entirely due to the use of check off glucose isomerase for the production of sweetening agents. Other commercial applications utilize penicillin acylase, fumarase, ?–galactosidase and amino acid acylase. Since 2000, although there has been consistent growth in enzyme markets, few new processes employing immobilized enzymes have been introduced. The following three examples highlight many of the how to example biochemical, technological and economic considerations relating to the use of immobilized enzymes on paper check, a commercial and industrial scale. Undoubtedly the invisible resume most significant large-scale application of paper check immobilized enzymes involves the production of high-fructose corn syrup (HFCS). On Advertising Is A? Although most of the general public believe that sucrose is responsible for the ‘sweetness’ of food and off, drinks, there have been significant efforts to help assignments uk replace sucrose with alternative, and often cheaper, soluble caloric sweetening agents. HFCS is check off a soluble sweetener that has been used in many carbonated soft drinks since the help assignments uk 1980s, including brand-name colas such as Coca-Cola and Pepsi-Cola.

HFCS is produced by the enzymatic digestion of starch derived from check off, corn (maize). Developments in HFCS production have been most prominent in countries such as the essay on advertising necessary U.S.A., which have a high capacity to produce starch in the form of paper off corn, but which do not cultivate significant amounts of help sugar cane or sugar beet, and must therefore import either the raw products (for processing) or the refined sugar (sucrose) itself. Simple corn syrups can be manufactured by breaking down starch derived from corn using the enzyme glucoamylase alone or in combination with ?-amylase. Paper? These enzymes are cheap and can be used in a soluble form. On Advertising Necessary Evil? Since starch has to be extracted from corn at high temperatures (because starch has poor solubility at paper check low temperatures and forms very viscous solutions), the process utilizes enzymes from thermophilic organisms, which have very high temperature optima. Simple corn syrup is therefore composed predominantly of a critical essay story glucose, which unfortunately has only 75% of the sweetness of off sucrose. However, in essay on advertising is a necessary, order to paper off make the syrup sweeter the enzyme glucose isomerase, which catalyses the following reaction, can be employed: This enzyme (described previously in the section on properties and mechanisms of enzyme action) will produce a roughly 50:50 mixture of glucose and fructose at equilibrium, and since fructose has 150% of the sweetness of sucrose, this glucose:fructose mixture will have a similar level of sweetness to sucrose.

However, glucose isomerase is an intracellular bacterial enzyme, and would be prohibitively expensive to use in a soluble form. This makes it an ideal candidate for use in an immobilized process. The first glucose isomerase enzyme to be isolated was obtained from species of Pseudomona s in 1957, and more useful enzymes were isolated throughout the essay 1960s from paper check, species of Bacillus and Streptomyces. In 1967, the Clinton Corn Processing Company of Iowa, U.S.A. (later renamed CPC International) introduced a batch process that utilized an invisible, immobilized glucose isomerase enzyme, and by 1972 the company had developed a continuous process for the manufacture of HFCS containing 42% fructose using a glucose isomerase enzyme immobilized on a DEAE ion-exchange support. During the late 1970s, advances in enzymology, process engineering and fractionation technology led to the production of syrups with a higher fructose content, and today HFCS containing 55% fructose is generally produced, and is commonly used in off, soft drinks, although 42% fructose syrups are still also produced for resume, use in some processes, including the production of bakery foodstuffs. In 2010, the U.S. production of HFCS was approximately 8 million metric tons, accounting for check, 37% of the a interview U.S. caloric sweetener market, and it is estimated that today about 5% of the entire corn crop in the U.S.A. is paper check off used to invisible produce HFCS. Within the dairy industry the paper off production of 1 kg of cheese requires about 10 litres of milk, and produces about 9 litres of whey as a waste product. Of Independence? Whey is a yellowish liquid containing 6% dry matter, of which nearly 80% is paper check off lactose. The enzyme lactase (?-galactosidase) may be used to break down lactose to its constituent monosaccharides, namely glucose and galactose, which are more soluble than lactose, and have potential uses as carbon sources in microbial fermentation, and can also be used as caloric sweeteners. Valio Ltd of Finland has developed arguably the most successful commercial process for invisible resume, the treatment of whey.

Using a lactase enzyme obtained from Aspergillus , immobilized by adsorption and cross-linked on to a support resin, whey syrups are produced that have been utilized as an ingredient in drinks, ice cream and confectionery products. The Aspergillus enzyme has an acid pH optimum of 3–5, and by operating at low pH the process avoids excessive microbial contamination. Treatment plants that utilize 600-litre columns have been built in Finland, and paper, these are used to treat 80 000 litres of whey per day. Of Independence? This technology has also been used to produce whey syrups in England (by Dairy Crest) and in Norway. Similar technology can also be used to remove lactose from milk. Paper Off? Lactose-free milk is produced for consumption by those who have lactose intolerance (a genetic condition), and also for consumption by pets such as cats, which are often unable to essay on declaration digest lactose easily. The first industrial processing facility to use immobilized lactase to treat milk was opened in paper off, 1975, when Centrale del Latte of Milan, Italy, utilized a batch process in which yeast ( Saccharomyces ) lactase, with a neutral pH optimum of is a necessary 6–8, was immobilized within hollow permeable fibres.

This process was capable of treating 10 000 litres of check off milk per day, and was operated at low temperature to resume prevent microbial contamination. Production of semi-synthetic penicillins. High yields of natural penicillins are obtained from species of the fungus Penicillium through fermentation processes. However, over the years many microbial pathogens have become resistant to natural penicillins, and off, are now only treatable with semi-synthetic derivatives. With? These are produced through cleavage of natural penicillin, such that the G or V side chain is removed from the check 6-aminopenicillanic acid (6-APA) nucleus of the molecule: Thereafter, by writing a critical essay story, attachment of a chemically different side chain, a semi-synthetic penicillin product (e.g. ampicillin, amoxicillin) can be formed. In addition, the 6-APA can undergo chemical ring expansion to yield 7-aminodesacetoxycephalosporanic acid (7-ADCA), which can then be used to generate a number of important cephalosporin antibiotics (e.g. cephalexin, cephradine, cefadroxil). The development of immobilized penicillin G acylase dates back to research conducted in 1969 by University College London and Beecham Pharmaceuticals in the U.K. Penicillin G acylases are intracellular enzymes found in E. Check? coli and a variety of other bacteria, and the Beecham process immobilized the E. coli enzyme on a DEAE ion-exchange support.

Later systems used more permanent covalent bonding to attach the enzyme to the support. In the 1980s and 1990s, world production of 10 best resume executives penicillins was dominated by European manufacturers, which accounted for production of around 30 000 tonnes of penicillin per annum, 75% of which was used for the manufacture of semi-synthetic penicillins and cephalosporins. Paper Check? However, over the past 10 years, due to essay increasing costs of labour, energy and raw materials, more bulk manufacturing has moved to the Far East, where China, Korea and India have become major producers. The market currently suffers from significant overcapacity, which has driven down the unit cost of check off penicillin and cephalosporin products. However, penicillins and 10 best writing executives, cephalosporins still represent one of the world's major biotechnology markets, with annual sales of about ?10 000 million, accounting for 65% of the entire global antibiotics market. Enzymes have a wide variety of uses in analytical procedures. Their specificity and potency allow both detection and amplification of a target analyte. ‘Wet chemistry’ enzyme-based assays for the detection and quantification of a variety of paper check off substances, including drugs, are widespread. Enzymes also play a key role in immunodiagnostics, often being used as the agent to amplify the signal—for example, in enzyme-linked immunosorbent assays (ELISAs). Within DNA-fingerprinting technology, the enzyme DNA polymerase plays a key role in the amplification of DNA molecules in the polymerase chain reaction. However, ‘wet chemistry’ analytical methods are increasingly being replaced by 10 best resume executives, the use of check biosensors—that is, self-contained integrated devices which incorporate a biological recognition component (usually an immobilized enzyme) and an electrochemical detector (known as a transducer). Much of the technological development of biosensors has been motivated by help, the need to measure blood glucose levels.

In 2000, the World Health Organization estimated that over 170 million people had diabetes, and predicted that this figure will rise to over 360 million by 2030. In view of this, many companies have made significant investments in RD programmes that have led to the availability of a wide variety of glucose biosensor devices. In 1962, Leland Clark Jr coined the check off term ‘enzyme electrode’ to describe a device in which a traditional electrode could be modified to respond to other materials by the inclusion of a nearby enzyme layer. Clark's ideas became a commercial reality in 1975 with the successful launch of the essay story Yellow Springs Instruments (YSI) model 23A glucose analyser. This device incorporated glucose oxidase together with a peroxide-sensitive electrode to off measure the hydrogen peroxide (H 2 O 2 ) produced during the following reaction: In this device, the essay is a necessary rate of H 2 O 2 formation is a measure of the rate of the reaction, which depends on the concentration of glucose in solution, thus allowing the latter to check off be estimated. As was discussed earlier, in enzyme-catalysed reactions the relationship between substrate concentration and reaction rate is not linear, but hyperbolic (as described by the Michaelis–Menten equation).

This is also true for the glucose oxidase within a biosensor. Resume Service Executives? However, we may engineer a more linear relationship by ensuring that the enzyme is either behind or within a membrane through which the check glucose must diffuse before it reacts with the enzyme. This means that the system becomes diffusionally, rather than kinetically, limited, and the response is then more linearly related to write report the concentration of glucose in solution. Over the years the YSI model 23A glucose analyser has been replaced by a range of much more advanced models. The current YSI model 2900 Series glucose analyser is shown in Figure 16. Paper Off? This instrument has a 96-sample rack that enables batches of samples to be run, with the analysis of each sample taking less than a minute.

The instrument can measure the invisible glucose content of whole blood, plasma or serum, and paper check off, requires only 10 ?l of sample per analysis. The membrane-bound glucose oxidase typically only needs to be replaced every 3 weeks, thereby reducing the cost of analysis. These systems also offer advanced data-handling and data-storage facilities. In addition, these instruments can be modified to is a necessary analyse a wide variety of other substances of off biological interest, simply by incorporating other oxidase enzymes into the membrane (Table 8). To enable diabetic patients to take their own blood glucose measurements, small hand-held biosensors have also been developed, which are in fact technologically more advanced because the enzyme and resume writing service, transducer are more intimately linked on the sensor surface.

The first device of this type was launched in 1986 by Medisense, and was based on technology developed in the U.K. at Cranfield and paper, Oxford Universities. The ExacTech blood glucose meter was the size and shape of a pen, and used disposable electrode strips. This device was followed by a credit card-style meter in 1989. Such devices again rely on glucose oxidase as the biological component, but do not measure the reaction rate via the production (and detection) of H 2 O 2 . Instead they rely on direct measurement of the resume writing rate of check electron flow from glucose to the electrode surface. How To A Interview Example? The reactions that occur within this device may be summarized as follows: and at the electrode surface: where GO x -FAD represents the FAD redox centre of glucose oxidase in its oxidized form, and GO x -FADH 2 represents the reduced form.

Basically electrons are removed from the glucose molecules and passed via the enzyme to the ferrocene mediator, which then donates them to the working electrode surface, resulting in the generation of an electrical current that is directly proportional to the rate of oxidation of glucose, and thus proportional to the glucose concentration in paper, the sample. Medisense, whose only resume executives, product was its blood glucose meter, was bought by Abbott Diagnostics in 1996, and Abbott-branded devices continued to use and develop this technology for some time. In 1999, Therasense marketed a glucose meter that represented the next generation of sensing technology, and off, integrated the enzyme even more closely with the electrode. Originally developed by Adam Heller at the University of Texas in the 1990s, wired-enzyme electrodes do not rely on resume, a soluble mediator such as the ferrocene used in the Medisense devices. Instead the enzyme is immobilized in an osmium-based polyvinyl imidazole hydrogel in which the electrons are passed from enzyme to electrode by a series of fixed electroactive osmium centres that shuttle the electrons onward in a process called ‘electron hopping.’ In 2004, Abbott Diagnostics purchased Therasense, and instruments such as the off FreeStyle Freedom Lite meter range produced by essay, Abbott Diabetes Care (Figure 17) now incorporate this wired-enzyme technology. Devices of this type are highly amenable to miniaturization. Continuous measuring devices are becoming increasingly available, and may well revolutionize the check off control of certain disease conditions. For example, with regard to on advertising necessary evil diabetes, devices such as the FreeStyle Navigator range from Abbott Diabetes Care use the same wired-enzyme technology as that described earlier, but now incorporate this into a tiny filament about the diameter of a thin hypodermic needle. This is inserted approximately 5 mm under the skin to measure the glucose level in paper off, the interstitial fluid that flows between the cells. The unit is designed to remain in situ for up to 5 days, during which time it can measure the glucose concentration every minute.

A wireless transmitter sends the glucose readings to a separate receiver anywhere within a 30-metre range, and this can then issue an early warning alarm to alert the user to how to a interview report a falling or rising glucose level in time for them to take appropriate action and avoid a hypoglycaemic or hyperglycaemic episode. In addition, experimental units have already been developed that link continuous glucose biosensor measurement systems with pumps capable of gradually dispensing insulin such that the diabetic condition is automatically and reliably controlled, thereby avoiding the traditional peaks and troughs in glucose levels that occur with conventional glucose measurement and the intermittent administration of paper check insulin. Therefore, looking to the future, we may confidently expect to see the essay on advertising is a necessary development of paper off biosensor systems that can continuously monitor a range of physiologically important analytes and automatically dispense the required medication to alleviate the symptoms of a number of is a necessary evil long-term chronic human illnesses. For the sake of conciseness, this guide has been limited to some of the off basic principles of 10 best writing service executives enzymology, together with an overview of the biotechnological applications of enzymes. It is important to understand the relationship between proteins and off, the nucleic acids (DNA and RNA) that provide the blueprint for the assembly of proteins within the help with assignments uk cell. Genetic engineering is thus predominantly concerned with modifying the proteins that a cell contains, and genetic defects (in medicine) generally relate to the abnormalities that occur in the proteins within cells. Much of the molecular age of biochemistry is therefore very much focused on the study of the check off cell, its enzymes and other proteins, and their functions. Abbreviations7-ADCA, 7-aminodesacetoxycephalosporanic acid; 6-APA, 6-aminopenicillanic acid; ATCase, aspartate transcarbamoylase; CSTR, continuous-flow stirred-tank reactor; CTP, cytidine triphosphate; DFP, diisopropyl fluorophosphate; EC, Enzyme Commission; ELISA, enzyme-linked immunosorbent assay; GUT, glucose-1-phosphate uridylyltransferase; HFCS, high-fructose corn syrup; PBR, packed-bed reactor; PFK, phosphofructokinase; STR, stirred-tank reactor. This article is a reviewed, revised and 10 best resume writing executives, updated version of the following ‘Biochemistry Across the School Curriculum’ (BASC) booklet: Teal A.R. Wymer P.E.O., 1995: Enzymes and their Role in off, Technology.

For further information and to provide feedback on this or any other Biochemical Society education resource, please contact education biochemistry.org . Help With? For further information on other Biochemical Society publications, please visit www.biochemistry.org/publications. This is an paper, open access article published by Portland Press Limited and distributed under the Creative Commons Attribution Licence 3.0.