Reforms of Diocletian - 1268 Words

Discuss the reforms of Diocletian. What were they, why did he think they were necessary, what impact long and short range. Be sure to include comments regarding dominate, tetrarchy (not year of 4 emperors), edict of Prices (Bailkey Lim) and Xp (Christians). Diocletian affects greatly the modern world. End of antiquity was around 9th century. Diocletian brought an end to the period popularly known to historians as the Crisis of the Third Century (235–284). He established an autocratic government and was responsible for laying the groundwork for the second phase of the Roman Empire, which is known variously as the Dominate (as opposed to the Principate instituted by Augustus), the Tetrarchy, or simply the Later Roman Empire.†¦show more content†¦Considering that during the half-century preceding Diocletian s ascension the empire had been in a nearly constant state of civil war, it is remarkable that the Tetrarchy did not immediately fall apart due to the greed of any of the four emperors. In 305, Diocletian retired and Maximian was persuaded to do the same. The two Caesars became the senior emperors as designed, but when it came time to choose new Caesars, the military and Senate intervened and brought forward their own candidates. In 306, Constantine started a civil war in the west, which he won in 312. He took the eastern half from Licinius by 324 and ruled the entire empire until his death in 337. Power was fractured again under Constantine s sons. Though the throne was nominally unified under, among others, Julian, Valentinian I, and Theodosius I, by 395 the division between the eastern and western halves was permanent. Economic reforms When Diocletian ascended to the throne, the Roman economy was on the verge of dissolution Five decades of civil war. The quickest and easiest solution to this problem was to debase the silver coinage, to print more money, as it were.[7] This resulted in extreme hyperinflation, mass distrust of imperial coinage, and, in some areas, localized regression to a barter economy Further, in 301, Diocletian attempted to curb the rampant inflation with his Edict on Maximum Prices. This edict fixed prices for over a thousand goods, fixed wages, andShow MoreRelatedThe World Of Antiquity, The Roman Empire Essay1678 Words   |  7 Pagesroman emperors come and go-from war, disease, famine, natural causes. At this point, the roman empire is going to collapse. General Diocletian takes over and gains power by defeating the last emperor. Diocletian saw an opportunity to reform, rebuild and restructure an antiquated empire. He s the man with plans. He made religious, administrative, economic and milit ary reforms. He thought that romans needed something to bind together, like a religion. He wanted emotional support with the government soRead MoreThe Collapse Of The Second Century Empire2171 Words   |  9 PagesWhen Diocletian came to power in 284 his aim was to return the empire back to stability and prosperity after the crisis that had plagued the third century. External pressures, such as the threat of barbarian invasion, worsened internal tensions such as economic depressions, civil war and an unstable administrative structure due to the growing influence and power of the army. Diocletian evidently saw the external threats of invasion and civil wars as the biggest threat to the stability of the empireRead MoreThe Battle Of The Byzantine Empire Essay1427 Words   |  6 Pageswho they saw as unfit. These themes were meant to allow the Empire easy access to an army but, even with all its benefits it still has its problems. Diocletian, when he took power in Rome, worked to calm the army and build up their defense. The army before Diocletian was only good at revolts, and not impressive at actually defending the empire. Diocletian built up the army and set standard pay for soldiers. He demanded that taxpayers either produce recruits or either find some means to support theRead MoreEvents During The Period Of The Republic932 Words   |  4 Pagessenatorial class. Peasants were driven off the land and into the cities. Most of the peasants were unemployed and lived by begging. The Populates demanded the redistributionoftheland to the dispossessed peasants who vere flooding into Rome, as well as a reform of the voting procedure. The struggle between these two factions came to civil war. Tiberius had been elected Tribune in 133 B.C.E. He proposed a land bill to the Assembly of Tribes that would effectively divide the land give it to the Roman citizenryRead MoreWhy did Rome fall?892 Words   |  4 Pagesnon- existent. Diocletian tried to make reforms to make the empire as strong as it was before. He realized that the empire was too large for one person to govern, he split the empire in half and took control of eastern part himself. He then appointed a co-emperor to rule in the west. He also reorganized the problems in the civil service and made them responsible directly to the emperor. He increased the size of the army and trained them better. To improve the economic health of the empire, Diocletian set limitsRead MoreEssay on The Fall of the Western Empire in the Fifth Century532 Words   |  3 PagesThis chaos brought the social and economic system to the point of collapse. Extraordinary leadership came from Diocletian who ruled from 284-305. He implemented a series of reforms such as his `Edict on Prices. He created what was known as a tetrarchy. This divided the empire, which eventually led to the collapse of the Roman Empire. On his voluntary retirement, Diocletian left two augusti to rule the divided eastern and western empire. However Augustus Constantine reunited the empire underRead MoreAnalysis Of The Novel Lost Of The West 1413 Words   |  6 Pagesinternal power struggles. When Diocletian comes into the picture; Brownworth almost recognizes as a savior to the Roman culture. Before going into the historically accurate means of Diocletian’s impressive power grab of Rome, Brownworth literally sated that salvation was brought to Rome by Diocletian, â€Å"Salvation came, unexpectedly enough, from Dalmatia. A tough soldier named Diocletian†(3). Throughout the chapter Brownworth almost tangibly slobbers over the idea of Diocletian and his somewhat revolutionaryRead MoreEssay on The Fall of Rome860 Words   |  4 Pagescenturies. Persia, at Rome’s expense, was ravaging provinces of the Middle East. With these events in process, the entire empire appeared on the brink of falling apart. The rescue of the failing Roman Empire came at last, in A.D. 284, when the ruler, Diocletian, came to power. He, unlike rulers before him, had the shrewdness and good fortune to survive, as a determined visionary and leader. He was born the son of a freed slave, enlisted in the ranks, and was eventually proclaimed emperor by his troopsRead MoreRoman Empire vs. Roman Rebublic Essay900 Words   |  4 Pagescome to an end and in return the roman empire was formed. In the roman empire the military was growing weak, the economy was falling and a lack of loyalty fell amongst the empire. Diocletian and Constantine passed reforms to help fix Rome like fixing the prices of goods and doubling the size of the military etc... Diocletian had realized that Rome was too large and divided it into two separate parts. The authoritarian policies we temporarily successful but it all came to an end when Constantine reunitedRead MoreDecline And Fall Of The Roman Empire1310 Words   |  6 Pagesthe weake ning of the Roman Empire. Inflation was caused during the Severus reign from 193-211. He increased Army pay drastically, which caused a devaluation of Roman currency. In fact, Severus nearly ruined the value of Roman coinage completely. Diocletian attempted to fix this inflation during his reign, reforming the tax system and tried to even out prices and wages. For the time, he manages to stabilize the Roman currency, however it was clear that the Roman Empire was on the downward spiral in

Symptoms And Symptoms Of Schizophrenia - 1153 Words

1 / 3 Cindy Tien 3-18-15 Per.6 Schizophrenia What is Schizophrenia? Can you imagine living day by day having to hear and see things that nobody else could? You feel alone, lost and different amongst other normal people. Believe it or not, approximately twenty five million people in America have been impacted by this disease called schizophrenia. What is schizophrenia? Schizophrenia is mental disorder distinguished by disturbances within thought patterns, attention, and emotions. Unfortunately, there is no known cure for schizophrenia, but researchers are working hard to find effective treatments for those suffering from this terrible disease. Signs and Symptoms of Schizophrenia Schizophrenics often suffer terrifying symptoms such†¦show more content†¦Delusions are false unshakable beliefs while hallucinations are incorrect perceptions of events or objects involving senses. Thought disorders (aka disorganized thinking) are dysfunctional ways of thinking that causes a person to talk in a garbled sort of way. In addition, patients with this disorder can make up meaningless words or â€Å"neologisms.† Movement disorders can appear as agitated body movements. People that are affected with this disorder may repeat certain motions over and over. It can become so extreme that the person may become catatonic or be in a state in which he or she does not move nor respond to others. If I were to be in such a state, I would not want to have anyone trying to keep me alive because my true self wouldn t be acknowledged. Negative Symptoms Unlike positive symptoms, negative symptoms are associated with disruptions to normal emotions. Patients with negative symptoms suffer from lack of pleasure in daily life, speak very little, and have a â€Å"flat affect† or talk in a dull or monotonous voice. These symptoms are harder 2 / 3 to recognize and can be mistaken for depression or other mental disorders. Research has shown that people who experience a lot of negative symptoms function worse than those who experience positive symptoms. The reason behind this is if you cannot speak, motivate

Has the Single Market project in Europe been a success Free Essays

Abstract The establishment of the EU’s single market was intended to create jobs and enhance prosperity. Since it was established in 1992, significant benefits have been made to the EU’s internal market and a lot of opportunities have been created. Despite this, many problems continue to exist and further changes are necessary if the objectives of the EU are to be fully realised (European Commission, 2012: 1). We will write a custom essay sample on Has the Single Market project in Europe been a success? or any similar topic only for you Order Now Introduction The idea behind the European Union’s (EU) single market was to treat the EU as one territory so that the free movement of people, goods, money and services could be achieved (Europa, 2012: 1). The single market was established by the EU to enhance competition and trade through a system of standardised laws that apply to all Member States (Barnard, 2002: 1). This improves efficiency and gives individuals more choice when it comes to providing and attaining goods and services. The overall quality of the goods and services is increased, which is economically beneficial. The Single European Act was enacted in 1986 to establish a single market and has since been considered one of the EU’s greatest achievements (Europa, 2012: 1). This led to the abolishment of internal border controls between EU countries in 1993 and is now accessible to millions of people across 27 Member States. Restrictions to trade have been removed and individuals now receive better standards of living. EU law comprises of treaties and legislative provisions, such as Directives and Regulations that aim to secure the free movement of goods, services, people, and capital. Despite this, Member States are still responsible for social welfare and taxation, yet the EU influences the policies of Member States (Europa, 2012: 1). The single market has been successful in allowing people and businesses to move freely within the European Economic Area (EEA) and has therefore transformed the way individuals live, work and travel (Mayes and Hart, 1994: 177). The progress that has been made towards the development of the EU’s single market will be identified in this study in order to determine the extent to which it has been a success. Barriers to the free movement of goods, services, people and capital The single market was intended to remove any barriers that restrict the free movement of goods, services, people and capital. A number of different policies have therefore been implemented that seek to remove any free movement restrictions (Mayes and Hart, 1994: 5). This has significantly impacted many organisations and industries within the internal market. However, unless EU policies are conformed to by all Member States it is unlikely that greater freedom will be attained within the EU. This is often at the expense of widely accepted practices; however this is considered necessary in achieving harmonisation. It therefore seems to be important that any barriers to trade are removed and that actions likely to impact sustainable development are eradicated. Article 101 of the Treaty on the Functioning of the European Union (TFEU) (ex Article 81 EC) provides that; â€Å"all agreements between undertakings, decisions by associations of undertakings and concerted practices which may aff ect trade between Member States and which have as their object or effect the prevention, restriction or distortion of competition within the internal market† shall be strictly prohibited. Any limitations that are placed upon the freedom to trade should therefore be prohibited so as to allow for the freedom of movement to be attained. Whether this is easy to establish in practice, is a debatable subject because although substantial improvements have been made in the 20 year history of the EU, it is clear that many obstacles still need to be overcome in guaranteeing a free market (Alam, 2007: 153). Single Market and Competition The establishment of the single market within the EU provides greater opportunities to businesses by providing them with access to the world’s largest trading bloc (Gov, 2013: 1). This enhances economic activity whilst also creating healthy competition through the stimulation of business and innovation. This leads to growth and job creation as export and trade will be increased Gov, 2013: 1). Not only does this have a beneficial impact upon the economy but it also increases productivity. Consumers also benefit from a single market as competition often leads to reduced costs for products and services. This was identified by Euromove when it was pointed out that competition is one of the main driving forces of an advanced modern economy as it â€Å"gives the consumer choice, it puts downward pressure on prices, it rewards innovation and it helps to create jobs (2009: 1). Nevertheless, in order to prevent unfairness and ensure that the single market is a level playing field, the EU has introduced various rules and principles that seek to create fair competition. Such principles impose a number of burdens upon businesses within the EU, although this is considered necessary in the proper functioning of the internal market. It was evidenced by Shuibhne that the establishment of the internal market created a different focus of competition law in terms of addressing the barriers to integration created by state intervention in the market and the problems that occurred as a result of the liberalisation processes of the 1990’s† (Shuibhne, 2006: 88). Whilst the legislative framework is now developed, on-going improvements continue to be made so that rules and regulations are being properly enforced and so that businesses and consumers understand the rules that exist within the internal market. This has been happening since the internal market was first established, so as to maintain an effective operation of the single market. Some of the improvements have included; improving and enforcing single market rules, reducing the regulatory burden imposed upon businesses, and the liberalisation of certain areas including; public procurement, public services and utilities (DTI, 2002: 1). In spite of these improvements, there are still many underlying weaknesses that exist in the single market which seems to suggest that it may not be as successful as originally anticipated in the internal market strategy. Some of these weaknesses have arisen as a result of; failures by Member States to implement some of the Directives (Kennedy, 2011: 108 ), a lack of co-operation that exists between Member States, or because of inadequate enforcement (Kennedy, 2011: 108). In 1999 the internal market strategy was put forward by the European Commission which set out the aims and objectives of the establishment of the internal market. Various measures were incorporated into this strategy which sought to guarantee the proper functioning of the single market. This strategy has since been reviewed on an annual basis, though it cannot be said that the internal market is complete. Therefore, despite the fact that many obstacles have already been removed by the EU, new challenges are continually being dealt with. It has been said that companies within the EU should take full advantage of the single market model since the free movement of capital, goods, services and labour would be realised more easily. Tax issues arising from cross-border mergers and acquisitions would effectively be minimised through economic integration. This was identified by Ilzkovitz et al; â€Å"the Internal Market is a powerful instrument to promote economic integration and to increase competition within the EU and it has been the source of large macro-economic benefits† (2007: 271). Arguably, it seems as though the main objective of the Single Market is to allow competition to be obtained through the ability to trade freely within the EU. In accordance with this, it would therefore be beneficial if EU Companies took full advantage of this market so as to avoid many issues that arise from various issues including the taxation issues that result from Merger and Acquisitions (MA) deals. Hence MA deals are structu red in a way that results in harsh tax liabilities and since an asset-based deal will â€Å"typically expose the seller to two levels of taxation, corporate and personal and a stock-based transaction can be unattractive to a buyer given the tax treatment of fixed asset values† (Q Finance, 2010: 1). If a company only conducts business within the single market, then they will not be exposed to such harsh tax liabilities. This encourages competition which is imperative for the advancement of the economy. However, because there are certain restrictions that exist within the single market, companies often find it difficult to expand their business in the internal market. Thus, as argued by the European Commission; â€Å"national tax systems in the EU differ so much that it can be complicated and expensive for companies to expand in the single market† (European Commission, 2011: 1). Because of these problems, a number of proposals were put forward by the Commission to eliminate these absurdities including the introduction of a single set of tax rules, also known as a Common Consolidated Corporate Tax Base (CCCTB). This would make it a lot easier and cheaper for companies to do business within the EU and as identified by Goodall; â€Å"every year the CCCTB will save businesses across the EU ˆ700 million in reduced compliance costs, and ˆ1.3 billion through consolidation† (2011: 53). The current problems that emerge from companies entering into MA dealings would be r emoved and harsh tax liabilities would be avoided. Long term administrative improvements would also be made for those companies operating in multiple member states (Drysdale, 2007: 66), which is welcoming for those companies wishing to save on taxation. The freedom of movement will be likely to be obtained more easily by the implementation of a CCCTB. This will certainly encourage competition within the single market and more companies would most likely enter into MA deals as a result. Conversely, not all agree that the CCCTB is effective, however, and as a result of this many Member States have refused to support its implementation. It is felt that a CCCTB would be a â€Å"de facto infringement of their tax sovereignty should such a Directive be written into law† (Ernst and Young, 2011: 40). This provides an example of how Member States will not implement every Directive that exists under EU and signifies how greater co-operation is needed. In spite of this, there are many drawbacks that exist within a CCCTB and it is questionable whether the tax advantages of a CCCTB outweigh the drawbacks that would arise if it was implemented. In addition, it was confirmed by the Secretary to the Treasury, Justice Greening, that the draft directive to introduce a CCCTB does not comply with the principles of subsidiarity and proportionality (Cave, 2011: 87). Furthermore, it is also unlikely that the government will agree to a proposal that might threaten or limit the UKâ €™s ability to shape its own tax policy (Cave, 2011: 87). In view of these assertions, it cannot be said that a CCCTB should be incorporated since it appears to be out of step with the principle of subsidiarity. This principle aimed to ensure that the EU only acted in instances where the proposed action could not be achieved by individual countries. Effectively, although there are many benefits of a CCCTB, there are also a significant amount of drawbacks that transpire and it seems as though the government ought to ensure that a CCCTB, if implemented, does not undermine competition, whilst also ensuring that extensive opportunities for tax avoidance are not created. It is arguable whether this can be achieved and it seems as though extra demands will in fact be placed upon corporate tax departments. Taxation Articles 25-31 and 39-60 of the Treaty on the Functioning of the European Union (TFEU) lay down the fundamental freedoms that are relevant to tax law and thus facilitate free movement of goods, services, persons and capital within the European Economic Area (EEA). Accordingly, as argued by Sypris, the changes made by the implementation of the TFEU; â€Å"influence the internal market case law of the Court of Justice, which represents a significant threat to national labour laws and practices† (2008; 219). The ECJ held in Gschwind v Finanzamt Aachen-Aubenstadt (Case C-391/97) [1999] ECR I-5451, [2001] STC 331, ECJ that direct taxation is a matter which â€Å"falls within the competence of Member States,† however, that competence must be exercised in accordance with EU law (Lee, 2010: 1473). This demonstrates how Member States no longer have complete control of their own laws and that the fundamental freedoms, enshrined under the TFEU, must also be taken into considerati on. As noted by Lee; â€Å"ever since the treaties first came into force, the fundamental freedoms have been interpreted broadly, so as to strike down domestic legal rules incompatible with an internal market† (2010: 1474). This is also exemplified under Article 26 which states that; â€Å"the Union shall adopt measures with the aim of establishing or ensuring the functioning of the internal market, in accordance with the relevant provisions of the Treaties.† Since the laws of all Member States must guarantee compliance with Treaty provisions, tax law will be affected. The ECJ’s decision in Cadbury Schweppes v Commissioners of the Inland Revenue Case C-196/04 [2006] 3 WLR 890 shows how EU law affects UK tax law. Here, it was held that the broad interpretation of the Controlled Foreign Companies (CFC) provisions were incompatible with EU law because of the restrictions that were being placed upon freedom of establishment under Article 56 of the TFEU (ex Article 49 EC). It was noted by the ECJ that â€Å"hindrance to freedom can only be justified on the ground of counteraction of tax avoidance if the legislation in question is specifically designed to exclude from a tax advantage wholly artificial arrangements aimed at circumventing national law.† Subsequent to this decision, significant amendments were made to the CFC rules under Schedule 16 of the Finance Act 2009 in order to ensure that EU law was being fully complied with. The Acceptable Distribution Policy (ADP) exemption was abolished and changes to the Income and Corporation Tax es Act 1988 (ICTA) were made by introducing a new section 751AA. This illustrates the importance of the single market and exemplified how UK tax law will be affected by the provisions contained in the EU. The same rules will also apply in relation to the other Member States, though not all agree that this is appropriate. Instead, it is argued that abuses of national law can be effectuated as a result of EU law provisions and that the legislation in question must not be used as a blanket method of justifying abuses such as tax avoidance† (Wellens, 2009: 1). In view of this, it is manifest that national courts are required to undertake a case by case approach when considering individual situations. Various harmonisation measures have been implemented by the EU to facilitate the integration into the single market, including; the merger directive, the parent/subsidiary directive and the interest and royalties directive. The Merger Directive was designed to facilitate mergers across European borders so that it would be easier for companies to engage in dealings, whilst also reducing the tax burden. This was intended to establish common rules governing the cross-border merger of companies within the EEA† (Cain, 2007: 2). It cannot be said that tax harmonisation has been created by the Directive (Bell, 2004: 1), which is again due to the relcuatnce of Member States to implement the Directive. Unless co-operation exists, the Directive cannot be fully utilised and tax harmonisation cannot be achieved. The Parent/Subsidiary Directive was designed to â€Å"grant cross-border transactions the same favourable treatment as is provided for equivalent purely domestic transactions† (Tiley, 2008: 34) and was to be applied to parent and subsidiary companies of Member States. Akin to the Merger Directive, the harmonisation of taxes was intended yet this does not appear to have been achieved as harmonisation is still lacking. Nevertheless, because companies within Member States are still being taxed on income that has been derived from substantial interests, the Directive is not being fully implemented which may be â€Å"contrary to the free movement of capital and freedom of establishment, as well as the Parent-Subsidiary Directive, because such income is as a rule exempt from taxation if derived by local parent companies† (Morgan, 2010: 18). Therefore, the extent to which these Directives are being utilised is debatable. The Interest and Royalties Directive intended to eliminate withholding tax obstacles in the area of cross-border interest and royalty payments within a group of companies (HM Revenue and Customs, 2003: 1). Under this Directive companie s are subjected to a reduced tax liability if their members dealt with each other within the EU. Nevertheless, because no single tax has been created it is questionable whether these Directives are in fact sufficient. Conclusion The establishment of the EU’s single market has brought about significant benefits for EU Member States. A large number of jobs have been created and the opportunities for individuals within the internal market have significantly increased. Regardless of this, the extent to which the objectives of the single market have been attained remains uncertain in light of the obstacles that transpire. It is often difficult to determine whether a free market is truly being achieved since there is a great deal of confliction that now exists. This can be seen in relation to the provisions contained in Article 101, which restrain the free flow of goods. This is clearly contrary the free movement provisions and the courts have been faced with much difficulty over the years as a result of this. In addition, there are many inherent difficulties that arise for companies who wish to enter the internal market and although the implementation of a Common Consolidated Corporate Tax Base (CCCTB) has been proposed, it has been said that this would create even more difficulties. Nevertheless, because taxation comes into conflict with the free movement provisions because of the fact that Member States no longer have complete control of their own laws, it seems as though a CCCTB would be beneficial. Because of these obstacles, it is thereby questionable whether the single market has been as successful as one would have hoped. References Alam, S. (2007) Sustainable Development and Free Trade: Institutional Approaches, Business Economics, London: Routledge. Barnard, C. (2002) The Law of the Single Market: Unpacking the Premises., Oxford: Hart Publishing. Bell, S., (2011) ‘Amendments to Merger Directive: A New Dawn for Cross-Border Reorganisations?’ (2004) International Bureau of Fiscal Documentation, [Online] Available: http://www.freshfields.com/publications/pdfs/practices/dfi030401.pdf [29 April, 2014]. Bently, L. and Sherman, B. (2008) Intellectual Property Law, 3rd Edition, Oxford: OUP. Cain, B., (2007) ‘Cross-Border Mergers Directive’ 31 Companies Secretary’s Review 9, Issue 2. Correa. C. M, Intellectual Property and Competition Law: Exploring Some Issues of Relevance to Developing Countries, ICTDS, Issue Paper No 21, ICTDS Programme on IRPs and Sustainable Development, (October, 2007), [Online] Available at: http://www.iprsonline.org/resources/docs/corea_Oct07.pdf [29 March 2014]. Cave, R., (2011) ‘EU Tax Developments’ 32 Tolley’s Practical Tax Newsletter 87, Issue 11. Drysdale, D., (2007) ‘HMRC, Business and the Tax Profession – An Uneasy Relationship’ 28 Tolley’s Practical Tax Newsletter 66, Issue 9. DTI., (2002) ‘Single Market’ [Online] Available: http://webarchive.nationalarchives.gov.uk/+/http://www.dti.gov.uk/europe/pagej.html [29 April, 2014]. Ernst Young., (2011) ‘EU: European Commission Publishes Final Common Consolidated Corporate Tax Base (CCCTB) Proposals’ News 16/03/2011 40LNB. Europa. (2012) ‘What is the Single Market’ [Online] Available: http://ec.europa.eu/internal_market/20years/singlemarket20/facts-figures/what-is-the-single-market_en.htm [30 March 2014]. European Commission. (2012) ‘The Single Market Act’ The EU Single Market, [01 April 2014]. Goodall, A., (2011) ‘EC Proposes ‘Common Tax Base’ 32 Tolley’s Practical Tax Newsletter 53, Issue 7. European Commission., (2000) ‘Communication on Services of General Interest in Europe’ 580 Final. Euromove., (2009) ‘EU Competition Policy’ [Online] Available: http://www.euromove.org.uk/index.php?id=6516 [29 April, 2014]. HM Revenue Customs., (2003) ‘INTM400010 – EU Interest and Royalties Directive: Overview of the Directive’ [Online] Available: http://www.hmrc.gov.uk/manuals/intmanual/intm400010.htm [29 April, 2014]. Ilzkovitz, F., Dierx, V., Kovacs, V., and Sousa, N., (2007) ‘Steps Toward a Deeper Economic Integration: The Internal Market in the 21st Century; A Contribution to the Single Market Review’ European Economy, European Commission, Economic Papers, No 271, [Online] Available: http://ec.europa.eu/economy_finance/publications/publication784_en.pdf [29 April 2014]. Kennedy, T. P., (2011) European Law, Oxford University Press: Oxford. Lee, N., (2010) Revenue Law Principles and Practice, 28th Edition, London: Bloomsbury Professional. Marquis. M. (2007) ’02 (Germany) v Commission and the Exotic Mysteries of Article 81 (1) EC)’ European Law Review 29, 1-6. Mayes, D. G. and Hart, P. (1994) The Single Market Programme as a Stimulus to Change: Comparisons Between Britain and Germany, Cambridge: Cambridge University Press. Morgan, C., (2010) ‘Analysis – International Review’ 1015 Tax Journal 18. O’Loghlin. R. (2003) ‘EC Competition Rules and Free Movement Rules: An Examination of the Parallels and Their Furtherance by the ECJ Wouters Decision’ European Competition Law Review 62, 224-237. Shuibhne, N. N. (2006) Regulating the Internal Market, Edward Elgar Publishing: London. Steiner, J. and Woods, L. (2009) EU Law, 10th Edition, Oxford: OUP. Syrpis, P., (2008) ‘The Treaty of Lisbon: Much Ado†¦But About What?’ Industrial Law Journal, 37 (219), Issue 3, 219-235. The European Commission., (2011) ‘Simpler Tax Rules for Businesses’ (2011) Europa, [Online] Available: http://ec.europa.eu/news/economy/110318_1_en.htm [29 April, 2014]. Tiley, J., (2008) Revenue Law, 6th edn Hart Publishing. Wellens, R., 2009. Cadbury Schweppes and beyond: the future of the UK CFC Rules. Tax Working Papers, [online] Available at http://ials.sas.ac.uk/postgrad/courses/docs/MA_Tax_Working_papers/Richard%20PUBLICATION%20Final.pdf [29 March 2014]. Wesseling, R. (1999) ‘The Commission White Paper on Modernisation of EC Antitrust Law’ (20 European Competition Law Review 427, 422-427. Q Finance., (2010) ‘Structuring MA Deals and Tax Planning’ [Online] Available: http://www.qfinance.com/mergers-and-acquisitions-checklists/structuring-m-and-a-deals-and-tax-planning [29 April, 2014]. How to cite Has the Single Market project in Europe been a success?, Essay examples

Strategies In Cancer Chemotherapy Cytarabine An Assessment Biology Essay Example For Students

Strategies In Cancer Chemotherapy Cytarabine An Assessment Biology Essay Cytarabine besides known as ( Ara-C ) is an endovenous chemotherapeutic drug normally used to handle acute myelocytic leukaemia. This is a malignant neoplastic disease situated on the myeloid line of blood cells, characterised by the rapid growing of unnatural white blood cells that accumulate in the bone marrow. Ara-C onslaughts both cancerous and non-cancerous cells as they undergo DNA synthesis. The mechanism of action of each drug is multifaceted but chiefly involves suppressing DNA synthesis. Ara-C is transported into the cell where it is activated by phosphorylation. Deoxyribonucleic acid reproduction occurs at the taking strand of the reproduction fork by add-on of the bases in the 5? A ; gt ; 3? way to organize one new girl strand. The 2nd girl strand consequences from reproduction of the lagging Deoxyribonucleic acid strand at the reproduction fork where the lagging strand replicates discontinuously and requires synthesis of a primer. Okazaki fragments are intermediates created from the lagging strand as a consequence. The rate of reproduction for atomic DNA is frequently elevated in malignant cells, peculiarly in aggressive tumors, comparative to environing healthy tissues. Disruption of DNA reproduction of malignant cells inhibits tumour growing and enlargement. Therefore interrupting DNA synthesis preferentially targets malignant cells. Ara-C feats this mechanism to stamp down tumour growing. Ara-C can make this because it is an parallel of cytidine and becomes misincorporated into DNA during reproduction alternatively of cytidine doing changes in the construction, stableness and protein adhering features of the girl DNA. Cytarabine inhibits DNA elongation, with suppression happening preponderantly at the lagging strand of the reproduction fork. It is besides an S-phase-specific agent upon activation and is a competitory inhibitor of DNA polymerase alpha and beta. Inhibition of DNA synthesis through premature concatenation expiration, competitory suppression and the inability of DNA polymerases to adhere adequately to DNA girl strands causes malignant cell programmed cell death. Drug Discovery: Cytarabine i.e. Ara-C was derived from cognition gained from the close scrutiny of bioactive Marine nucleosides, found in the marine environment. Cytarabine is an illustration of a marine-derived drug. The drug was foremost discovered in 1945 by a chemist named Werner Bergmann who collected sponges from the shallow Waterss from Elliot Key, Florida. This unidentified species called Cryptotethia crypta named by Dr. M. W. De Laubenfels discovered more of these sponges off the Islands in the Bahamas. Upon closer scrutiny by the manner of boiling the sponges in propanone in a Soxhlet extractor setup, Bergmann observed crystalline stuff separated from the propanone. This stray stuff was found to be a constituent in a mixture of drugs used for the intervention for acute lymphoblastic leukaemia. UV analysis in the signifier of an soaking up spectrum that was similar to the construction of the nucleotide thymidine. This new compound similar to thymidine was named spongothymidine since the co mpound was derived from sponges. This led to the find that a nucleoside has biological activity. The subsequent detonation of compounds and these finds led to the designation of a close parallel, C arabinoside, as powerful antileukemic agent and was later commercialised by Upjohn ( now known as Pharmacia ) as Ara-C. Other near compounds such as Ara-A were synthesised and commercialised by Burroughs Wellcome ( now GSK ) . Computer assisted drug design can be used to happen the chief active binding sites. These adhering sites correspondent to deoxycytidine place important bindings to functional groups besides present within DNA in cancerous cells, i.e. the mark enzymes involved in DNA synthesis. Computer assisted drug design allows the drug design to be similar in construction to cytidine i.e. be a cytidine parallel. .ucd6731d3378c12d53f9033b05dbcb0ff , .ucd6731d3378c12d53f9033b05dbcb0ff .postImageUrl , .ucd6731d3378c12d53f9033b05dbcb0ff .centered-text-area { min-height: 80px; position: relative; } .ucd6731d3378c12d53f9033b05dbcb0ff , .ucd6731d3378c12d53f9033b05dbcb0ff:hover , .ucd6731d3378c12d53f9033b05dbcb0ff:visited , .ucd6731d3378c12d53f9033b05dbcb0ff:active { border:0!important; } .ucd6731d3378c12d53f9033b05dbcb0ff .clearfix:after { content: ""; display: table; clear: both; } .ucd6731d3378c12d53f9033b05dbcb0ff { display: block; transition: background-color 250ms; webkit-transition: background-color 250ms; width: 100%; opacity: 1; transition: opacity 250ms; webkit-transition: opacity 250ms; background-color: #95A5A6; } .ucd6731d3378c12d53f9033b05dbcb0ff:active , .ucd6731d3378c12d53f9033b05dbcb0ff:hover { opacity: 1; transition: opacity 250ms; webkit-transition: opacity 250ms; background-color: #2C3E50; } .ucd6731d3378c12d53f9033b05dbcb0ff .centered-text-area { width: 100%; position: relative ; } .ucd6731d3378c12d53f9033b05dbcb0ff .ctaText { border-bottom: 0 solid #fff; color: #2980B9; font-size: 16px; font-weight: bold; margin: 0; padding: 0; text-decoration: underline; } .ucd6731d3378c12d53f9033b05dbcb0ff .postTitle { color: #FFFFFF; font-size: 16px; font-weight: 600; margin: 0; padding: 0; width: 100%; } .ucd6731d3378c12d53f9033b05dbcb0ff .ctaButton { background-color: #7F8C8D!important; color: #2980B9; border: none; border-radius: 3px; box-shadow: none; font-size: 14px; font-weight: bold; line-height: 26px; moz-border-radius: 3px; text-align: center; text-decoration: none; text-shadow: none; width: 80px; min-height: 80px; background: url(https://artscolumbia.org/wp-content/plugins/intelly-related-posts/assets/images/simple-arrow.png)no-repeat; position: absolute; right: 0; top: 0; } .ucd6731d3378c12d53f9033b05dbcb0ff:hover .ctaButton { background-color: #34495E!important; } .ucd6731d3378c12d53f9033b05dbcb0ff .centered-text { display: table; height: 80px; padding-left : 18px; top: 0; } .ucd6731d3378c12d53f9033b05dbcb0ff .ucd6731d3378c12d53f9033b05dbcb0ff-content { display: table-cell; margin: 0; padding: 0; padding-right: 108px; position: relative; vertical-align: middle; width: 100%; } .ucd6731d3378c12d53f9033b05dbcb0ff:after { content: ""; display: block; clear: both; } READ: Pearl Harbor Conspiracy EssayActive site volumes of dCKc and dCKm were calculated by bring forthing the adhering pockets of the enzymes. These of which are similar to the construction of Ara-C: Drug Synthesis: It is possible to synthesize cytarabine, ara-C utilizing the undermentioned synthesis path. This path is besides used and established for the synthesis of ara-AC, an ara-C derived function. This derivative contains an excess N heteroatom within the ring. The first measure in the synthesis path involves hydrogenation of the initial compound utilizing H over a palladium accelerator. This is an illustration of a heterogeneous accelerator that provides a surface for the reactant molecules. The reactant is placed in an ethanolic H chloride solution taking to the decrease of the dual bond. The following phase in the synthesis path is intervention of the 2nd compound at room temperature with bis-trimethylsilyl-trifluoroacetamide ( BFTFA ) in acetonitrile solution produced the pentakis-trimethylsilyl derived function. This is allowed to reflux for several hours until full transition to the last merchandise ara-C is completed. Vaporization of the reaction solution produces syrup where it is boiled in methyl alcohol to take trimethylsilyl groups by solvolysis. Ara-C is so crystallised from the solution as a consequence. Drug Selectivity, authority and SAR: Cytarabine chief mark i.e. selectivity is indistinguishable to that of the nucleoside deoxycytidine due to the fact it is a nucleoside parallel. It acts chiefly as a competitory inhibitor to cytidine triphosphate. Ara-C is metabolised in vivo to ara-CTP and competes with CTP during DNA synthesis with Deoxyribonucleic acid polymerases both alpha and beta. To exercise its cytoxic effects, cytarabine is converted ab initio to the 5-phosphate via rate restricting phosphorylation catalyzed by deoxycytidine kinase ( dCK ) in tumor cells and so finally to its 5-triphosphate ara-CTP. Ara-CTP presumably Acts of the Apostless both by suppressing the binding of 2-deoxycytidine triphosphate to DNA polymerase and by incorporation into stretching DNA strands, ensuing in faulty ligation or uncomplete synthesis of Deoxyribonucleic acid fragments and finally cell decease programmed cell death. Targets of this chemotherapeutic drug besides include adhering sites of the correspondent molecule cytidine. The authority of the ara-C is nevertheless limited in its public-service corporation as an anti-cancer nucleoside because of hapless intracellular conveyance features. Besides it has a weak activity as a substrate for tumor cell kinases. Therefore the development of drug opposition as a consequence from reduced nucleoside kinase activity as lowered the efficaciousness of this agent. Tumour cells deficient in dCK ( deoxycytidine kinase ) are extremely immune to cytarabine, so intramolecular bringing of ara-CMP might be expected to besiege opposition in these cells. Ara-C and similar nucleoside parallels enter cells via specific transporters which are indispensable to ara-C cytotoxicity in human tumor cells. Hence nucleoside transporter lacking cells are extremely immune to cytarabine. Therefore to turn to this job a prodrug of cytarabine is synthesised and used alternatively which can spread passively into cells where it is metabolised into an active signifier, i.e. intracellular activation, and therefore overcomes resistance jobs such as restricting nucleoside transporters. An illustration of a prodrug is cytarabine phosphoramidate. An in-vitro survey assay on tumor malignant lymphoid cells indicated the drug inhibited cell growing up to 50 % of the control value, where the stock drug was prepared in absolute ethyl alcohol. This process was undertaken in a 72h incubation period where information recorded fitted a sigmoid curve and the consequences were expressed as the IC50. Other surveies in vivo conducted on mice with grafted human malignant neoplastic diseases of different types. Cytarabine is effectual against malignant neoplastic disease cells within mice B and mice D. It has some authority against malignant neoplastic disease cells C but opposition develops as a consequence and it is uneffective against A. The structure-activity relationship, i.e. the relationship between the chemical construction of the molecule and its biological activity is the biological responsiveness with G in DNA reproduction, correspondent to cytidine guanine interactions. The SAR constituents of cytarabine are therefore as follows and derived from cytidine. Besides similar in SAR and responsiveness is gemcitabine which works in an tantamount manner to both cytarabine and cytidine but marks lung malignant neoplastic disease, pancreatic malignant neoplastic disease and chest malignant neoplastic disease cells. .u93a20a8093ad6771a70f021d605269be , .u93a20a8093ad6771a70f021d605269be .postImageUrl , .u93a20a8093ad6771a70f021d605269be .centered-text-area { min-height: 80px; position: relative; } .u93a20a8093ad6771a70f021d605269be , .u93a20a8093ad6771a70f021d605269be:hover , .u93a20a8093ad6771a70f021d605269be:visited , .u93a20a8093ad6771a70f021d605269be:active { border:0!important; } .u93a20a8093ad6771a70f021d605269be .clearfix:after { content: ""; display: table; clear: both; } .u93a20a8093ad6771a70f021d605269be { display: block; transition: background-color 250ms; webkit-transition: background-color 250ms; width: 100%; opacity: 1; transition: opacity 250ms; webkit-transition: opacity 250ms; background-color: #95A5A6; } .u93a20a8093ad6771a70f021d605269be:active , .u93a20a8093ad6771a70f021d605269be:hover { opacity: 1; transition: opacity 250ms; webkit-transition: opacity 250ms; background-color: #2C3E50; } .u93a20a8093ad6771a70f021d605269be .centered-text-area { width: 100%; position: relative ; } .u93a20a8093ad6771a70f021d605269be .ctaText { border-bottom: 0 solid #fff; color: #2980B9; font-size: 16px; font-weight: bold; margin: 0; padding: 0; text-decoration: underline; } .u93a20a8093ad6771a70f021d605269be .postTitle { color: #FFFFFF; font-size: 16px; font-weight: 600; margin: 0; padding: 0; width: 100%; } .u93a20a8093ad6771a70f021d605269be .ctaButton { background-color: #7F8C8D!important; color: #2980B9; border: none; border-radius: 3px; box-shadow: none; font-size: 14px; font-weight: bold; line-height: 26px; moz-border-radius: 3px; text-align: center; text-decoration: none; text-shadow: none; width: 80px; min-height: 80px; background: url(https://artscolumbia.org/wp-content/plugins/intelly-related-posts/assets/images/simple-arrow.png)no-repeat; position: absolute; right: 0; top: 0; } .u93a20a8093ad6771a70f021d605269be:hover .ctaButton { background-color: #34495E!important; } .u93a20a8093ad6771a70f021d605269be .centered-text { display: table; height: 80px; padding-left : 18px; top: 0; } .u93a20a8093ad6771a70f021d605269be .u93a20a8093ad6771a70f021d605269be-content { display: table-cell; margin: 0; padding: 0; padding-right: 108px; position: relative; vertical-align: middle; width: 100%; } .u93a20a8093ad6771a70f021d605269be:after { content: ""; display: block; clear: both; } READ: Roots of AntiSemitism EssayAn of import portion of ara-C in conformity to its structural activity relationship lies on the phosphorylation as discussed earlier for this compound ; a close analogy is cytidine and similar in construction gemcitabine phosphorylation by dCK. This SAR constituent is on the OH group to bottom left of the O heteratom in the ring, which becomes phosphorylated.