Development of Insulin using Recombinant DNA Technologies

Development of Insulin using Recombinant desoxyribonucleic acid TechnologiesAlistair JonesThe use of biotechnology within music diabetes and ripening of insulin using recombinant DNA technologiesAbstractProteins act as a catalyst for metabolous reactions and responsible for inter and intracellular reactions and signalling events essential for life(Ferrer-Miralles, et al., 2009) Diabetes mellitus is a metabolous disorder with numerous aetiologies it can be defined by chronic hyperglycaemia which go away cause an military force on the metabolism of carbohydrates, fats and proteins. This detrimental lay out is from the lack of insulin action, insulin secretion or a compounding of them both(prenominal). Diabetes causes vast term damage, dysfunction and failure of a range of major organs. (Consulation, 1999) Through the use of clinical administration missing proteins can be sourced from external sources to reach normal concentrations within the tissular or systemic level. As a nu mber of important studies develop all confirmed the importance of the use of strengthened insulin treatment for the reduction and minimisation of long term diabetic complications it is of great importance and pharmaceutical nourish that human proteins can be sourced (Lindholm, 2002) Through the use of biochemical and genetic knowledge the work of insulin has become available and this industrial scale of therapeutic protein doing is the send-off true application of recombinant DNA technology. (Swartz, 2001, Walsh, 2003) E.coli can be considered as the first microorganism for the production of proteins and is primarily used for genetic modification, cloning and low production for research purposes. Many historical developments within molecular genetics and microbic physiology fetch been based within this species which has results in a collection of both information and molecular tools. (Ferrer-Miralles, et al., 2009)DiscussionProteins act as a catalyst for metabolic reactions a nd responsible for inter and intracellular reactions and signalling events essential for life consequently , a deficiency in the production of polypeptides or production of non- working(a) of relevant proteins will derive in pathologies which can range from mild to severe (Ferrer-Miralles, et al., 2009).Diabetes mellitus is a metabolic disorder with numerous aetiologies it can be defined by chronic hyperglycaemia which will cause an effect on the metabolism of carbohydrates, fats and proteins. This detrimental effect is from the lack of insulin action, insulin secretion or a combination of them both. Diabetes causes long term damage, dysfunction and failure of a range of major organs. The characteristics presented with diabetes be weight loss, polyuria, blurring of fancy and thirst the more severe cases will cause ketoacidosis or a non-ketotic hypersmolar state which will lead onto comas, stupor and left untreated death. As the symptoms are a lot not severe and go undetected for long periods of time, hyperglycaemia can cause pathological and functional changes before a diagnosing can be made. Diabetes causes a multitude of long term affects which include, but not limited to the failure of the renal system, a two to four generation increased risk of cardiovascular disease and potential blindness. There are a number of pathogenetic processes which can be involved in the development of diabetes these will include the processes which destroy the insulin creating beta cells within the pancreas and the creation of a resistance to insulin action ( Alberti, et al., 2006, Consulation, 1999)A combination of metabolic disorders known as metabolic syndrome (MetS) is the combination of hyperglycaemia, hypertension and gout and other cardiovascular risk factors which predict a high risk of developing diabetes. People who have MetS are of the highest risk of the development of type 2 diabetes as it is present up to five times higher within people with this syndrome this is collect to the fact that glucose dysregulation is already present (Alberti, et al., 2006). slip 2 diabetes and atherosclerotic cardiovascular disease can be seen to be of similar ascendants. Inflammation markers have been associated with the development of type 2 diabetes in adults although this whitethorn be part of the autoimmune response they will also reflect the pathogenesis (Schmidt, et al., 1999)Abnormal metabolism of proteins, fats and carbohydrates is caused by the deficient insulin action on target tissues due to the insensitivity or lack of insulin. (Consulation, 1999) Through the use of clinical administration missing proteins can be sourced from external sources to reach normal concentrations within the tissular or systemic level. As a number of important studies have all confirmed the importance of the use of strengthened insulin treatment for the reduction and minimisation of long term diabetic complications with human insulin being the first line of treatment i t is of great importance and pharmaceutical value that human proteins can be sourced, as this is difficult to do from natural sources (Lindholm, 2002) . We are far past the times of animal sourced insulins and we are reaching the turning point in the use of recombinant DNA technologies which were developed during the late 70s and uses E.coli as a biological framework for the production of proteins of interest through relatively inexpensive procedures. Recombinant DNA technology not only offers the ability to create straightforward proteins but also cans the tools to produce protein molecules with alternative and modified features. (Mariusz, 2011) There are several obstacles in the production of proteins through the use of E.coli however, as it lacks the ability to arrest post-translational modifications (PTMs) present within the majority of eukaryotic proteins (Ferrer-Miralles, et al., 2009). Recombinant DNA insulins are, therefore, gradually being replaced by the more highly effi cient insulin analogues (Bell, 2007, Ferrer-Miralles, et al., 2009).Clinically, insulin analogues have been used since the late 1990s, the reason behind insulin modification for subcutaneous injection is to produce absorption properties that better eccentric the rate of supply from the injection to the physiological need. (Jonassen, et al., 2012) Insulin analogues have the properties of being able to be either rapid acting such as glusine, aspart or lispro or be a long lasting molecule such as glargine and detemir, these can also be used in combination with protamine, these premixed insulins provide a more sustained action (Bell, 2007).The combination of biotechnology and the pharmaceutical industry is a product of an evolution within technology and product insertion which has become a result in advances within science and business practices. The biotechnology based products are thought of as intelligent pharmaceuticals as they often provide new modes and mechanisms in the action and approach to disease control with improved success rate and better patient care. (Evens Kaitin, 2014) Through the use of biochemical and genetic knowledge the production of insulin has become available and this industrial scale of therapeutic protein production is the first true application of recombinant DNA technology. (Swartz, 2001, Walsh, 2003) Although, as insulin is take in such high volumes the product yields of the vast amount of the soon available secretory systems are not currently sufficient enough to make it fully competitive. The current ideas and strategies being used to help improve the efficiency and productivity of secretion are numerous. (Schmidt, 2004)Cultivation of insulin can be done hands down within microbial cells such as bacteria and yeast. During the 80s the FDA approved the use of human insulin produced from recombinant E.coli for the treatment of diabetes, this was the first recombinant protein pharmaceutical to enter the market. convey to the ver satility and possibilities created through the use of recombinant protein production a large sector of opportunities for pharmaceutical companies opened up. (Ferrer-Miralles, et al., 2009) Since the approval of insulin in 1982 there are now currently more than 200 biotech products available commercially and research has expanded this to over 900 products being tested within clinical trials. Pharmaceuticals are engaged within the development of these products advantageously as well as their commercialisation (Evens Kaitin, 2014). This acknowledges the fact that although the microbial systems lack the post translational modifications they are able to efficiently and conveniently produce functional mammalian recombinant proteins. Specific strains of many microbial species have now been created and adapted towards protein production and the incorporation of yeasts and eukaryotic systems is now in place for protein production. (Ferrer-Miralles, et al., 2009).The use of E.coli contempl ation system is the preferable choice for production of therapeutic proteins, amongst the 151 pharmaceuticals licensed in January 2009 30% where obtained in E.coli, this is due its ability to allow for efficient and economical production of proteins on both a lab scale and within industry (Mariusz, 2011, Swartz, 2001). During insulin production within E.coli the gene is fused with a synthetic fragment encryption for two IgG binding domains which have been derived from staphylococcal protein A. This product is then secreted into the growth medium of E.coli and purified using the IgG affinity. (Moks, et al., 1987)E.coli can be considered as the first microorganism for the production of proteins and is primarily used for genetic modification, cloning and small-scale production for research purposes. Many historical developments within molecular genetics and microbial physiology have been based within this species which has results in a collection of both information and molecular tools . (Ferrer-Miralles, et al., 2009) E.coli flourishes at a temperature of 37C but the proteins are in in dissoluble form. Fusion protein technology has been able to increase the solubility of over expressed proteins, through the modification of selected amino acid residues allowing for the collection of soluble proteins (Zhang, et al., 1998).Due to the lack of the mechanisms to enable PTMs in bacterial cells protein maturation and disulfide bridges can be, to an extent overcome through the use of protein applied science (Mariusz, 2011). PTMs are all-important(a) in protein folding, stability, processing and activity therefore, proteins lacking the PMTs may be unstable, insoluble or inactive. However it is possible to synthetically bind PTMs to products, and through genetic engineering of DNA, the amino acid sequence of the polysaccharide can be changed to alter its properties this has been observed within insulin. (Ferrer-Miralles, et al., 2009) For more sophisticated modifications the genetic fusion of two proteins is necessary (Mariusz, 2011) An increase number of proteins being produced are engineered and tailored to display altered pharmacokinetic profiles and reduce immunogenicity. (Walsh, 2003)Even with the pharmaceutical market progressively producing more protein drugs from non-microbial systems cell-free protein entailment and oxidative cytoplasmic folding offers alternatives to the standard recombinant production techniques, it has not effect or impaired the development and progression of products developed within microbial systems proving the cogency of the microbial systems. (Ferrer-Miralles, et al., 2009, Swartz, 2001)In the future Radio Frequency Identification technology will play an important role however there are some(a) barriers in place for the pharmaceutical supply chain, as there have been concerns raised concerning the potential detrimental effect on the proteins due to the electromagnetic exposure. Alterations have been detected afte r the RFID however the effect and damages to the protein remain unknown (Acierno, et al., 2010)Works CitedAcierno, R. et al., 2010. Potential effects of RFID systems on biotechnology insulin preparation A pack using HPLC and NMR spectroscopy. Complex Medical engineering (CME), pp. 198 203.Alberti, K. G. M. M., Zimmet, P. Shaw, J., 2006. Metabolic syndromea new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabetic Medicine, 23(5), pp. 469-480.Bell, D., 2007. Insulin therapy in diabetes mellitus how can the currently available injectable insulins be most prudently and efficaciously utilised?. Drugs, 67(13), pp. 1813-1827.Consulation, 1999. Definition, diagnosis and classification of diabetes mellitus and its complications. W. H. O., Volume 1.Evens, R. Kaitin, K., 2014. The Biotechnology Innovation MachineA credit of Intelligent Biopharmaceuticals for the Pharma Industry Mapping Biotechnologys Success. Pre press submitted to Clinical Pha rmacology Therapeutics, Volume Last excessed, 27/03/2014, p. Avalible from http//www.nature.com/clpt/journal/vaop/naam/abs/clpt201414a.html.Ferrer-Miralles, N. et al., 2009. Microbial factories for recombinant pharmaceuticals. Microbial stall Factories , 8(7).Jonassen, I. et al., 2012. Design of the Novel Protraction Mechanism of Insulin Degludec, an Ultra-long-Acting Basal Insulin. Online Available at http//link.springer.com/article/10.1007/s11095-012-0739-z/fulltext.html Accessed 2014 March 27.Lindholm, A., 2002. New insulins in the treatment of diabetes mellitus.. Best Pract Res Clin Gastroenterol, 16(3), pp. 475-92.Mariusz, K., 2011. Engineering of Therapeutic Proteins Production in Escherichia coli. Current Pharmaceutical Biotechnology, 12(2), pp. 268-274.Moks, T. et al., 1987. LargeScale Affinity Purification of Human InsulinLike Growth Factor I from gardening Medium of Escherichia Coli. Nature Biotechnology, Volume 5, pp. 379-382.Schmidt, F., 2004. Recombinant expression s ystems in the pharmaceutical industry. Applied Microbiology and Biotechnology, 65(4), pp. 363-372.Schmidt, M. et al., 1999. Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities study) a cohort study. The Lancet, 353(9165), p. 16491652.Swartz, J., 2001. Advances in Escherichia coli production of therapeutic proteins. Current Opinion in Biotechnology, 12(2), pp. 195-201.Walsh, G., 2003. Pharmaceutical biotechnology products approved within the European Union. European Journal of Pharmaceutics and Biopharmaceutics, 55(1), pp. 3-10.Zhang, Y. et al., 1998. Expression of eucaryotic Proteins in Soluble Form in Escherichia coli. Protein Expression and Purification, 12(2), pp. 159-165.

Analysis The Uk Oil And Gas Industry Environmental Sciences Essay

Analysis The Uk anoint And throttle valve patience Environmental Sciences testifyWith this report is a PESTE Analysis of The Upstream Oil and Gas effort in the United Kingdom. An analysis of the factors affecting the industry shows that it ope poses under legal, monetary and surroundingsal regulations where prices are determined by world-wide organisations like the makeup of Petroleum Exporting Countries (OPEC) and the Organisation of economic Cooperation and Development (OECD). The Upstream Oil and Gas industry in the United Kingdom is a mature peerless, and after 40 years of offshore geographic expedition, the country remains self sufficient in anoint and gas. This is an important sector for the UK, supplying the majority of the countrys vigor needs, and virtu each(prenominal)y all the countrys transport fuel. Economic factors that affect the industry are fossil oil color demand, price, return, investment and employment. sensory faculty of sustainable ontogeny and re pertlyable energy sources is the major social factor. engineering plays a crucial role in reducing the costs of geographic expedition and production of oil and gas, in addition to making the process safer and more environmental friendly. There is considerable attention being paid to the affect of oil exploration operations on the environment, and this leave also determine the future of the industry. The triple scenarios that can emerge for the industry mainly depend upon the oil and gas militia left in the sum ocean, the viability of their exploration and the development of alternative re impudentlyable energy sources.Introduction PESTE Analysis of the UK Upstream Oil Gas exertionWhat is a PESTE Analysis?PESTE shows which international factors are influencing a business or an industry, also measuring the market authorization and situation.This report is to understand and assess the various determinates of the external environment that influences the UK Upstream Oil Gas Industry. The factors assessed include Political, Economic, Socio-cultural, Technological and bionomic. Once completed this PESTE model go forth provide an in-depth understanding of the situational factors that affect and have the potential to affect the UK Upstream Oil Gas Industry presently and in the future.Political / Legal FactorsPolitical stability and a good law and localise situation are conducive to the smooth functioning of the upstream oil industry. Wars and terrorism can prove detrimental to operations. There are also some(prenominal) legislations passed by individual governments and associations who affect the functioning of the industry.2.1 LegislationThe Upstream Oil Industry in the United Kingdom is well regulated. In addition to the laws and regulations organisation business in general, there are several laws that pertain to the Oil Industry specifically.Petroleum Act 1998 (www.hmso.gov.uk/acts/acts1998/19980017.htm)Hydrocarbons Licensing Directive Regula tions 1995 (http//www.hmso.gov.uk/si/si1995/Uksi_19951434_en_1.htm)Master Deed establishment 2003 (www.gnn.gov.uk/gnn/national.nsf)The Offshore Installations (Emergency Pollution Control) Regulations 2002 (http//www.legislation.hmso.gov.uk/si/si2002/20021861.htm)The Offshore Chemicals Regulations 2002 (http//www.legislation.hmso.gov.uk/si/si2002/20021355.htm)The Offshore Combustion Installations (Prevention and Control of Pollution) Regulations 2001(http//www.legislation.hmso.gov.uk/si/si2001/20011091.htm)The Offshore Petroleum Activities (Conservation of Habitats) Regulations 2001 (http//www.legislation.hmso.gov.uk/si/si2001/20011754.htm)2.2 TaxationThe North sea Tax regime has three tiers, Petroleum Revenue Tax (PRT), Corporation Tax and a Supplementary Charge of 10%. The Budget proposals for 2004 are to exterminate from the scope of PRT, new tariff business.2.3 OPEC OECDThe Organisation of Petroleum Exporting Countries (OPEC) was framinged in 1960 with 5 members. By the end of 1971 six other nations had joined. OPEC stabilizes prices in the international Oil markets with a locating to eliminate fluctuations, by setting the production quotas in the member countries. Oil Price History Analysis. WTRG EconomicsIn contrast, the Organisation of Economic Cooperation and Development (OECD) was instituted to counterbalance the role of OPEC and has a membership of 30 countries. The core of original members was located in Europe and North America alone has expanded to include Asia, Latin America and the former Soviet bloc.Economic FactorsAs in every industry, there are economic factors affecting the health of the industry. It is abundantly clear that economic growth lead remain the primary driver of energy demand.3.1 World Economic Growth Oil DemandThe spherical economy has grown at an average rate of active 3% per year since 1970, and the expectation is that it allow for continue to grow at the same footmark over the next two decades (Raymond, Lee R., (2003). The most important factor governing upstream activities is the demand for Oil, which continues to affix.3.2 Oil PricesCrude oil prices behave more as any other commodity with wide price swings in times of shortage or oversupply. Currently the Brent Crude price is or so $30 per barreland is heavily influenced by the current world oil price set by the OPEC and OECD.3.3 Oil ProductionThe current production rate is around 4.25 million boe per day (North Sea Oil Leopard Magazine 2003) this is expected to decline to 3.6 million boe per day by 2005. By 2010 the government has a bearing of 3 million boe per day, although some industry experts reckon that production get outing be below 2.5 million boe per day.3.4 Employment in the Oil IndustryThe Oil Gas Industry in the UK, employs around 300,000 staff in exploration and production. Skill levels and multi-skill training are important issues keeping in view the engineering improvements.3.5 Financial InvestmentInvestment in upst ream infrastructure like pipelines, tankers etc. results in more exploration activity.Socio-Cultural FactorsThe Upstream Oil Gas Industry is indirectly affected by socio-cultural factors.4.1 Awareness about Sustainable DevelopmentConservationists and more recently the general public are showing concern about saving non-renewable energy sources and switching to renewable energy sources.4.2 Health Safety at rigsThe perception of the Oil Industry has always been that it is a dangerous environment to work. Since the Piper Alpha disaster there has been a more conscious effort by the HSE and Industry bodies to make it a safer place to work. With the perception now changing the UK Upstream Oil Industry is now attracting a better quality of manpower.Technological FactorsNew upstream technologies provide increase access to economically exploitable new liquids and gas reserves and reduce exploration, development and production costs. They result also mitigate adverse environmental efforts and risks to public health and safety from exploration and production activities.Technology and RD activities will be responsible for the development of alternative energy sources.5.1 Improvements in Oil Exploration ProductionIn the past 10 to 15 years research and development within Oil and Service Companies has seen the development of powerful new and advanced technologies and tools for use in exploration, reservoir valuation and production. Some of these are3D, 4D, 4C Seismic Imaging.Horizontal, Directional and Multilateral Drilling.Advanced Drilling Completion and Stimulation Technologies.Logging Tools and Nuclear Magnetic Resonance Imaging (NMRI). nimble Completion Reservoir Life Extension.New Energy Technologies in Upstream Oil Gas. The Middle East Economic Survey. 28th October 20025.2 Renewable Energy TechnologyThere are a wide range of renewable energy sources available and in the process of development and use. These are Biomass, Electricity, Geothermal, Hydropower, So lar, Wind and Tidal energy.Ecological / Environmental FactorsThe exploration, drilling and use of oil and gas will have to be kept in check due to the detrimental effects on the world ecosystem.6.1 Ecological ImpactThe ecology of the North Sea has deteriorated over 30 years of oil exploitation in spite of anti taint regulations. Discharges of oil and chemicals have various lethal and non-lethal effects on fish, birds, molluscs, cetaceans and other mammals (The Oil Gas Industry A guide for UK Activists. Corporate Watch.) Seismic surveying, drilling and rig installation cause disturbance to seabed ecosystems. The numbers of certain varieties of fish have reduced drastically.6.2 Climate ChangeThe rampant use of oil and petroleum products leads to Carbon Monoxide emissions (The Oil Gas Industry A guide for UK Activists. Corporate Watch), resulting in the greenhouse effect. It has been proved that there is a rise in temperatures, which will eventually lead to the melting of icecaps , the reversing of the Gulf Stream, and eventually great changes in climate all over the world. Flooding and coastal erosion will lead to massive population migration and loss of infrastructure all over the world.Significant Issues / Trends in the UK Upstream Oil Industry7.1 Reserves in the North Sea BasinThere are 260 oil and gas fields currently under development or in production on the UKCS (248 in 2001), with remaining reserves in these developments of around 11 billion boe (Alexanders Oil Gas 2002). At the current rate of production, it will take around 10 years for the oil and gas to be exhausted. The future of the industry depends upon new finds and further development of breathing fields7.2 Viability of ExplorationInitial indications from a new survey reveal the UK offshore oil and gas industry has reached a critical point in terms of its international competitiveness, with projections of investment growth non being matched by increased production volumes. New technologic al developments in the upstream oil field aim to improve recovery rates of existing reserves (typically only 35% of which are currently recoverable by primary and secondary recovery technologies) and also reduce relative costs.The volatility of the oil price has led to changes in the structure of the oil sector. There has been consolidation both horizontally and vertically in the traditional contracting supply chain. OPEC will continue to be a major force in setting world oil prices. Over 1998 / 1999 there was a severe reduction in oil price, but increases in the oil price since the end of 1999 have improved the change flow for oil companies, however the recovery for the industry will depend on technology transfer and new oil finds.7.3 Development of Alternative Energy SourcesTechnology has come a long way in recent years with individuals, communities and businesses recognising the benefits of switching to renewable energy.The Energy Saving Trust was set up by the UK Government aft er the 1992 Rio Earth Summit and is one of the UKs leading organisations investigating the development of alternative energy sources. Their goal is to achieve the sustainable, efficient use of energy and to cut carbon dioxide emissions being the key indorser to global warming. The use of alternative energy sources is one way to address this vital goal.Scenarios for the UK Upstream Oil IndustryBased on the above three issues that affect the upstream oil industry in the next decade, there could be three scenarios the optimistic, the pessimistic and the middle of the road.8.1 Optimistic ScenarioThe need for affordable and tonic energy will continue to increase, especially in growing economies as energy is of fundamental importance for the development of societies. The consumption of primary energy sources will increase over the next 20 year forecast and most of the increment in energy consumption will be in the form of fossil fuels (oil, natural gas, and coal). It is expected that fo ssil fuel prices will remain relatively low, and the cost of generating energy from renewable sources will not be competitive.The fiscal climate of the UK will encourage the long-term investment necessary to secure the development of those supplies. In the UK, PILOT a partnership of the UK Oil and Gas Industry and Government, will fulfill its vision set out for 2010. Over the next 25 years, the UK upstream industry will make 130 new discoveries and 240 new developments. Oil prices will stay at a high level and long term investment in new technology will increase productivity and find new sources of oil and gas. (About Pilot What is Pilot? Pilot. 2003)The industry will achieve a production level of 3 million place of oil equivalent per day in 2010 and a sustained investment level of 3 billion per year. There will be a 50% increase in the value of industry-related exports by 2005 and additional revenue of 1 billion from new businesses. There will also be a draw out self-sufficien cy in oil and gas for the UK with 100,000 more jobs than there would otherwise have been in 2010. (About Pilot What is Pilot? Pilot. 20038.2 Pessimistic ScenarioEnvironmentalists and pro-conservation groups will influence all countries to maintain the delicate ecological balance of the planet by stopping the use of fossil fuels. UK government policy and programs will back alternative energy sources and the electricity generated will rise. At the regional level, the Energy Saving Trust will work with local authorities and a range of organisations to promote the capital punishment of alternative energy sources.The environmental programs and government policies, particularly those designed to limit or reduce greenhouse gas emissions will be implemented. More indorse and financial funding for long-term renewable options to bring viable options to the market will achieve this. The Government will exceed its committed target and will achieve a 50% renewables target by 2010. The manufac turing sector all over the world will proactively implement methods to use renewable sources of energy.In view of this, the price of oil will plummet, due to cleaner and cheaper alternatives for energy being available. The OPEC will loose control over regulating oil and the market will be competing with other sources of energy. This will reduce the investment in the upstream oil sector and the transfer of technology for exploiting oil more efficiently will slow down. Eventually, the phasing out and decommissioning of Oil rigs in the North Sea will commence earlier than expected.8.3 Middle of the Road ScenarioThe production of oil and gas in the UK peaked in 1999 and will continue to decrease over the years if there are no new significant discoveries in the North Sea Basin (Analysis of the UK Oil Production. PeakOil. 22nd February 2001). In the meantime renewable energy sources will get a boost with more funding and research development efforts being committed in that direction.The new technologies being used to make oil exploration more cost effective will not be transferred effectively to the rig, due to a lack of investment and funding. The price of oil will not be high enough for a comfortable cash flow in the upstream oil industry. The OECD will govern the prices of energy, as it will more and more become non-fossil fuel based. UK will export most of its oil to the developing countries whose infrastructure would not have been upgraded enough to use renewable sources of energy.ConclusionOn analysing the PESTE factors affecting the Upstream Oil industry, it is apparent that the major issues that will impact the health and longevity of the industry are the remaining reserves in the mature North Sea Basin, the viability of exploration and the development of alternative renewable sources of energy. From my readings I feel that with the technology that is constantly being developed by the Oil companies Exploration and Production in the Upstream Oil and Gas Ind ustry in the United Kingdom will continue steadily for at least another 20 years.Even with renewable energy sources becoming increasingly more evident, oil and gas will remain the most important fuels for the next 20-30 years.ReferencesInternet1.Industry survey reveals challenges ahead for UK offshore oil and gas. Alexanders Gas Oil Connections. 27th November 2002.2.Analysis of the UK Oil Production. PeakOil. 22nd February 2001.3.The Oil Gas Industry A guide for UK Activists. Corporate Watch. Raymond, Lee R., (2003) The Petroleum Industry in the twenty-first Century Building on a Great Legacy. World Energy. 6 (2) 24-29 4.About Pilot What is Pilot. Pilot.5.UKOOA Sustainability Strategy Striking a Balance. UKOOA. 2002.6.North Sea Oil Leopard Magazine professor Alex Kemp7.North Sea Oil and the UK Economy. UKOOA.8.Oil Price History Analysis. WTRG Economics. 22nd9.Is OPEC necessary? Oil Online. 25th November 2002. 10.New Energy Technologies in Upstream Oil Gas. The Middle East E conomic Survey. 28th October 2002.11.Forces Driving the Petroleum Industry in 2000 and beyond.Energy Saving Trust Website

Study Proposal: Causative Mutations in Optic Neuropathy

Study Proposal Causative Mutations in Optic NeuropathyOptic neuropathy refers to degeneration of center marrow. It is often described as optic atrophy that doer loss of few or most of optic aspect fibers 1. It give the bounce be symmetric or bilateral based on toxic or nutritional ( vitamin B12 or folate deficiency) insults and transmittable defects 4. In genetically inherited optic atrophies, retinal ganglion cells and optic nerve fiber layer be ravishd. This damage can be focal (affects macular beam of optic nerve) or generalized 6. The axons of retinal ganglion cells arise from retina and from optic nerve. The optic nerve enter cortex via optic disc where input signal is processed into vision. The retinal ganglion cells or nerve cells of inner retina form 1.2 million nerve fibers 1. The find features of optic neuropathy results from death of these nerve cells or neurons.Autosomal recessive optic atrophies (ROAs) indicate loss of nerve fibers that form optic disc, optic ne rve, optic chiasm and optic tracts net bookmark. The only key feature of isolated ROAs is optic nerve degeneration. To date defects in genes coding for mitochondrial proteins leads to isolated ROAs 4.The genetically inherited atrophies can be familial that follows Mendelian ruler of inheritance (X-linked recessive, autosomal recessive and autosomal dominant) or non Mendelian (mitochondrial) 2. In autosomal recessive Mendelian pattern of inheritance, two copies of edition allele in touch on person and iodine copy of mutant allele in carrier are present. When two carriers mate, there is an equal chance (25%) of being affect and un change. There is a 50% chance of being heterozygous (unaffected carrier). But in autosomal dominant pattern of inheritance, affected individuals have one mutant copy of allele so every individual has 50% chance of being affected or being normal.In the pure congenital autosomal recessive optic atrophy, symptoms like visual impairment appear very early an d are present at birth or appear in first year of life. Affected individuals are severely impaired visually leading to visual disability or complete blindness. It is never associated with neurological disobliges. It can be diagnosed very early, usually before the age of 4 years. Fundus examination reveals optic disc pallor temporally or bilaterally. A cupping whitethorn develop with age 3. Affected individuals suffer from central scotoma, photophobia and also have red green food color confusion 6. Family history is critical for diagnosis Hereditaryopticneuropathies from clinical signs to diagnosis.Clinical diagnosis bear ons fundoscopy, visual field testing, fluorescein angiography, optical coherence tomography scan of the retinal nerve fiber layers, color vision compend and standard electroretinogram. Damage from optic nerve atrophy cannot be reversed 4.To clinically distinguishes it from LHON flourscene angiography was done which fails to show any peripapillary microvascular changes, beside this retinal drill is also normal confirmed by electroretinogram. Pathology of arOA is confirmed by testing visual evoked potential which was totally absent in affected individuals. interchange or cecocentral faults are diagnosed through visual field testing. Lesion in the fovea or papillomacular bundle leads to cental scotoma which ultimately affects the central fixation. Thinning of retinal nerve fiber layer is diagnosed through optical coherence tomography scan 3, 4, clinical diagnosis. Papillomacular bundle leads to the extension of cecocentral sctoma towards blind spot.There is no effective discourse for optic atrophy because degeneration of nerve fibers is irreversible process. Although further damage can be prevented by early diagnosis and by treating underlying causes of the disorder net bookmark. As environmental factor play their role in every aspect of life likewise in this disorder alcohol breathing in and smoking should be strictly prohibited Heredi taryopticneuropathies from clinical signs to diagnosis. Genetic counseling and proper awareness of people is very important to prevent such genetic disorders without any effective treatment.New therapies are being formulated by plan animal models or by clinical trial on affected humans these therapies mainly focuses in preventing oxidative stress. Animal models have been designed for testing the various treatments in case of Leber hereditary optic neuropathy Treatment of hereditaryopticneuropathies.arOA is divided into syndromic and non-syndromic form, syndromic arOA involve multiple organs other than eye which are effected just like wolfram syndrome 6, net bookmarks. While in non-syndromic optic nerve is affected only and it also shows familial transmission more than one members of same family can also be affected Hereditaryopticneuropathies from clinical signs to diagnosis.OPA 6 and 7 are the two loci which are characterized till now, magnetic variation in any one of two leads t o arOA. Disease create gene has been localized at chromosome 8q21q22 (Zmax of 3.41 at h0 for D8S270). D8S1794 and D8S1702 markers present on OPA6 in a 12Mb interval 6. OPA7 containing 40 known genes, only one gene TMEM126A screened as a causative mover of non-syndromic arOA 4, 7. TMEM126A is homozygous nonsense mutation characterized as first known mutation in case of isolated arOA, this gene transcribed into mitochondrial transmembrane protein.TMEM126A helps in early nucleation of mitochondrial complexes that is wherefore it is also termed as mitochondria-localized mRNA (MLR) protein. It play important role in function of retinal ganglion cells by arranging protein complexes essential for the proper functioning of RGCs. It is hypothesized that TMEM126A may accelerate the rate at which protein complex assemble, which otherwise occurs slowly that ultimately affect high energy demanding RGCs. While in other tissues the effect of this mutation may be substituted by some other prote in of TMEM family 4, 7.TMEM126A transcribe single ubiquitous transcript of 770bp that contain total five exons four coding and one non-coding exon. TMEM126A present on chromosome 11 and its span is 8.5 kb. Testis, fetal retinal pigmentary epithelium (RPE), fetal retina, brain (whole), cerebellum, fetal brain and skeletal muscle are the sites where unfaltering expression of TMEM126A has been observed. Substantial amount of specific mRNA in the ganglion cell layer, optic nerve head, the outer ellipsoide length of photoreceptor inner segments, and the outer plexiform layer is notice by the process of insitu hybridization in mouse i.e. 8 month old. In the photoreceptor outer segments and outer nuclear layer (ONL) no labeling is noticed. Mitochondria specific of import subunit of the ATP synthase is Immunolocalized on retinal sections of the same mouse which resulted into the same pattern of expression. So it is confirmed that TMEM126A transcribe mitochondrial localized m RNA.Linkage analysis is the process helps in finding mutation or gene resulted into arOA. Potential functionality of genes with their chromosomal location is associated through this statistical method. During chromosomal recombination markers present closely or on the same area on chromosome leave alone remain attached together are transmitted as such in offsprings this idea is exploited in linkage analysis. If in an individual disease gene is transmitted along with some specific markers it means disease causing gene is present close to these markers. Those disorders that follow Mendelian inheritance pattern can easily be analyzed through this process 5.This study will be the first step which further helps in identifying the causative gene responsible for arOA in Pakistani population and also help in designing therapeutic tools for the benefit of affected persons. By conducting these type of studies we can also aware our population about such type of rare disorders.

Factors that Affect Profitability Essay -- Business, Exporting, Forei

Procedures that you need to follow when exportingAfter establishing that South Korea is an economy with an increasingly more liberal economy, there are some problems for foreign transfer investment, mainly through non-transparency and burdensome regulations (Heritage Foundation). In order to draw off it a step further and to perform a complete analysis of the business environment, it is incumbent to compare the business procedures when doing business. As an industry, the imports of foreign goods procedure will be analyzed and contrasted with neighboring countries in order to guard a complete jibe of the business environment. Firstly, The country of interest South Korea. In what the import of foreign goods is concerned, South Korea has a comparatively quick and easy process. Importing procedures are estimated to take 7 long time, (2 days for each preparation of documents, port handling and inland handling and approximately 1 day for customs clearance). The cost of the procedures for the 7 days is estimated to be $790 (World Bank Doing Business, 2011). This information, at first glance seems positive. The procedures are fairly quick and the $790 cost is not an absurd essence of money paid in order to import goods. The bureaucracy is simple. The documents needed are the bill of lading, customs import declaration and terminal handling receipts (World Bank Doing Business, 2011). Corruption lore IndexThe latest corruption perception index by transparency international in 2008 includes five sets of data. These include the 2008 Corruption Perception Index (CPI) score, the amount of surveys used, the standard deviation, the high low range and the confidence range. Before the analysis of the data, it is important to understand what ea... ...). The Heritage Foundation has ranked South Korea with a genuinely low score of 55 out of 100, which might imply that corruption is widespread and there is still a long way to go to have a positive rating. (Heritage Foundati on, 2011)10)Labor FreedomLabor freedom has the lowest score of 46.5 out of 100. This shows that there are various problems regarding labor, a clear lawsuit is the very high cost of firing an employee whilst the non salary cost of employing a worker are moderate (Heritage, 2011).In conclusion, the overall freedom of the country is relatively positive. The ratings of the Heritage Foundation are fairly high, above the world average for the most part. Additionally, the government involvement in business is quite low compared to some other countries and at least it is not widespread to a degree to which investors would be fearful to engage in business.

Toys :: essays research papers

Toys"R"UsINTRODUCTIONIn this assignment I have chosen to steering on explaining what kind of company Toys"R"Us is, giving a brief, short summary of the firms history, their corporate responsibilities, what their competitive advantages are and how they implement their strategies through retail and merchandise. I also found it relevant to explain the market situation in the toy-industry and what the trends are, for understanding what other difficulties that are important to consider in set to survive.SHORT HISTORYIn 1948, a company which tot wholey dedicated themselves to children and their needs, was formed by Charles Lazarus in Washington DC. This was a perfect timing in relation to the post-war baby boom period, the demand for accessories for children was high, and the main purpose for the company was to carry furniture for babies. After some time, he heard customers saying phrases the like "I need a toy for my baby", so he began selling toys aswell. Mr.L anzarus tried to give his customers what they wanted he understood early that this was the topper way to keep his customers. In 1957, he opened his first toy supermarket, and with specialized retailing and the off-price positioning, he revolutionized the concepts in the pre-m every and discount days. After this success, he change his business to Interstate, which later went bankrupt. Mr.Lazarus rejoined the company and made it profitable, and in 1978 it became a public company Toys"R"Us,Inc.DIVISION OF THE COMPANYToday, Toys"R"Us is a $11 billion dollar company and they have over 1500 stores over the whole world. The company is divided into six different divisionsToys"R"Us US            strongly focuses on strengthening the obtain experience                     by providing better service and better merchandise. There are    &n bsp           around 680 locations of Toys R Us in the US.Toys"R"Us International      Is licensed, franchised and operated through over 570                     locations in 29 countries outside the USKids"R"Us           Consists of more than 375 locations where childrens                     clothing and toys are all under one roof, and oughts to offer                     all of the latest fashions and of course high quality                     merchandise.ImaginariumToysrus.com           Developed in alliance w ith Amazon.com in order to offer an                     online shopping service.Babies"R"Us           Offers everything parents need for their babies, like                     furniture, bedding, car seats etc. All products can be                     purchased under one roofBy organizing their organic law into these different divisions, it gives them a competitive advantage because it makes it easier to focus in the certain areas. These divisions are very different from each other, and needs specialization in all the different aspects.

Comparing Steppenwolf and the Teenaged Girl Essays -- Comparison Compa

Parallels Between Steppenwolf and the Teenaged Girl To be a teen girl means many things in this modern society. There are numerous expectations set for the average sixteen year old female she moldiness be pretty, popular, thin, preferably intelligent, but not too intelligent, and she must subjugate her will to the group. This world has a tendency to shun females who are too independent, who look too much power, and who attempt to break from the stereotypical female mold. I have personally see this spurning, especially from my peers. There exists a dichotomy somewhere in my own soul, a rift between that which I am expected to be and who I really am. Harry Haller, in Hermann Hesses novel Steppenwolf, experienced a similar predicament. He was torn between the life of a socially acceptable, decent man, and the primal, lupine nature of the Steppenwolf. I find myself caught between missing to be a socially acceptable, popular girl, and being the independent, intellectual, and strong p erson that I actually am. There are a number of parallels between Haller and I, each(prenominal) further proving that the dichotomy of the Steppenwolf and the division inwardly myself, the teenaged girl, are of the same essence. Often in my life I have felt trapped by the boundaries and expectations that those around me have set for how I ought to behave, think, and feel. Here in suburban America, these boundaries are often set by peers and family, as well as by the media and celebrity figures. The expectations that they have set often dictate ideas that, deep down, I greatly disagree with. One of the most prominent of the ideas is that my worth is reflected in my external physical appearance. In this world which has declared war on th... ...conditioned self and the true self. She both wishes to be accepted and to be set free from the groups expectations. She wants the thoroughgoing(a) body and face and yet realizes the lack of importance therein. Harry Haller, in the end, coul d not completely understand the game of life, but understood that the willingness to play and the intensity to sort through the inner self are what really matter. I have realized that, in the end, I must learn the same lesson. The passage ahead will not be easy, just as Harrys journey was long and arduous. Fear and fleeing are no longer options, though. It is an archetypal, inherent knowledge within each human being that self-knowledge is key to a true existence, and both the Steppenwolf and the teenaged girl realize the importance of this expedition. Works CitedHesse, Hermann. Steppenwolf. New York Henry Holt and Company, 1990.

Loss of Identity in the Techno-Culture Essay -- Clubbing Partying Tech

I began my doubt into the techno-sublime by keying the term techno-sublime into Googe to see if the term had been coined before. Whilst in that respect was no exact match, the first site that opened was http//www.sublime.net.au/chillout.html, The Chillout . unite is a planetary experience. I had presbyopic been interested in the event of the techno-dance party, that total awesome experience where there is a collapse of individuality and a loss of individual boundaries as I become part of the collective techno-experience. It was uncanny to find myself at this site in search of the techno-sublime and yet it was scarcely this exstasis or loss of identity in the face of the awesomeness of the techno-experience that was central to my understanding of the experience of the techno-sublime.1 Ben Malbons (1999) study, Clubbing Dancing, Ecstacy and Vitality, has proved invaluable in providing support for my elaboration of the techno-sublime. Whilst Malbons dissertation is different from m y own, the responses of some of his respondents as well(p) as his own diary entries have become very important in supporting my thesis that there is a loss of identity or estasis within the particular experience of techno-culture that is clubbing. Thus in a diary entry, titled 4 a.m. - lost for words, lost in time and space, just lost., Malbon writes We all seemed to urgency the music to take us over to become us in some way.. Clubbers were losing it all over the tush ... people are just so close to each other proximately and emotionally.. The intensity of this fusion of motions and emotions was almost overwhelming. (Malbon 1999xii) This diary entry, in particular, speaks of an experience in which his scent out of identity and rationality is subsum... ...nd vitality, London Routledge.Newman, Barnett (1948) The wondrous is now in Harrison, C.Wood, P. (ed) (1994) Art in theory 1900 - 1990 an anthology of changing ideas, Oxford, Blackwell 572-574.Nye, D.E. (1994) American Technol ogical Sublime, Cambridge Mass MIT Press.Storr, A. (1992) Music and the Mind, London harper Collins.Notes1I had begun my inquiry into the techno-sublime by arguing that in creative practice there occurs a particular flux that I have termed working hot. When star is working hot, I have argued, the transaction produces a dynamical relation where the work of art performs rather than represents. In this space, or state, I argued there is exstasis, or a loss of identity.2 My elaboration of the techno-sublime has been sensible by Christine Battersbys and Barbara Freemans theorization of the feminine sublime. Loss of Identity in the Techno-Culture Essay -- Clubbing Partying TechI began my inquiry into the techno-sublime by keying the term techno-sublime into Googe to see if the term had been coined before. Whilst there was no exact match, the first site that opened was http//www.sublime.net.au/chillout.html, The Chillout . clubbing is a planetary experience. I had long been interested in the event of the techno-dance party, that total awesome experience where there is a collapse of individuality and a loss of individual boundaries as I become part of the collective techno-experience. It was uncanny to find myself at this site in search of the techno-sublime and yet it was precisely this exstasis or loss of identity in the face of the awesomeness of the techno-experience that was central to my understanding of the experience of the techno-sublime.1 Ben Malbons (1999) study, Clubbing Dancing, Ecstacy and Vitality, has proved invaluable in providing support for my elaboration of the techno-sublime. Whilst Malbons thesis is different from my own, the responses of some of his respondents as well as his own diary entries have become very important in supporting my thesis that there is a loss of identity or estasis within the particular experience of techno-culture that is clubbing. Thus in a diary entry, titled 4 a.m. - lost for words, lost in time and space, just lost., Malbon writes We all seemed to want the music to take us over to become us in some way.. Clubbers were losing it all over the place ... people are just so close to each other proximately and emotionally.. The intensity of this fusion of motions and emotions was almost overwhelming. (Malbon 1999xii) This diary entry, in particular, speaks of an experience in which his sense of identity and rationality is subsum... ...nd vitality, London Routledge.Newman, Barnett (1948) The Sublime is now in Harrison, C.Wood, P. (ed) (1994) Art in theory 1900 - 1990 an anthology of changing ideas, Oxford, Blackwell 572-574.Nye, D.E. (1994) American Technological Sublime, Cambridge Mass MIT Press.Storr, A. (1992) Music and the Mind, London Harper Collins.Notes1I had begun my inquiry into the techno-sublime by arguing that in creative practice there occurs a particular flux that I have termed working hot. When one is working hot, I have argued, the performance produces a dynamical relation where the work of art performs rather than represents. In this space, or state, I argued there is exstasis, or a loss of identity.2 My elaboration of the techno-sublime has been informed by Christine Battersbys and Barbara Freemans theorization of the feminine sublime.