Banking Crisis Essay Example | Topics and Well Written Essays - 5000 words

Banking Crisis - Essay Example The crisis is thus perceived to have occurred as the result of exposure to Market Risks due to such risk transfer mechanisms (Banks normally are never exposed to market risks because they reply on internal systems in managing the credits) that caused many loopholes in the Credit Risk Management in management of lending to Sub-Prime customers. These customers are individuals or companies who do not have clean credit history or regular source of income. The Banks & Financial Institutions preferred to lend loans to Sub-Prime customers to avail the benefits of higher interest rates at a perceived calculated exposure of the investment capital to higher risks. To facilitate this in a secured and manageable manner, the banks & financial institutions used the mechanism of "Securitization" that essentially is the mechanism of distributing the risk of the lending to the investors outside the Banking system through a process. The process of "Securitization" resulted in the boom of Credit Deriva tive Market and was used extensively in the US Sub-Prime Mortgage Market by increasing the number of risky products but still reduce the liabilities on their balance sheets (thus shielding the same from external auditors). The money was shown to be flowing through so called "conduits" from investors to the borrowers through the SPV and SIV system. As described by experts the primary drawbacks that occurred in this process are poor valuations of assets acquired against the credit instruments thus resulting in uncertain asset valuation & high credit risk exposure that couldn't detect the imperfections in the Credit Markets. Even the external rating agencies got trapped in this mirage and couldn't predict the Sub-Prime crisis because the Securitization Process was extremely complex and the dependency was upon scattered and unreliable data outside the core banking system. Moreover, the Bank's risk assessment didn't demonstrate due diligence in screening the sub-prime borrowers and infor ming the investors about the associated risks in the so called securitized products. The overall system expanded uncontrollably and the competition became very stringent resulting in loans getting sanctioned at the flash of light and there was no time for adequate risk management. The actual risks ware completely covered under hyped data and analytics about the new credit instruments which, frankly no one understood correctly - not even the external auditors and the statutory & governance

Masks and Disguise Essay Example for Free

Masks and Disguise Essay In William Golding’s novel ‘Lord of the Flies’ and Shakespeare’s play ‘Romeo and Juliet’ masks and disguises are used to serve different purposes. Both texts use masks and disguise to allow characters to behave in ways that they usually would not or could not. For example, in Lord of the Flies, the boys go from being civilised to becoming savage. This is evident when it says â€Å"the mask was a thing on its own, behind which Jack hid, liberated from shame and self consciousness†. The fact that the mask is â€Å"a thing on its own† shows that the boys, Jack in particular, feel as if they are not responsible for their actions because of the mask. This is supported by the quote â€Å"The mask compelled them.† It also suggests that the boys have become completely different people after wearing the mask. The word â€Å"hid† suggests that the boys are also protected from the repercussions of their violent actions because the mask creates anonymity. At the masquerade ball in Romeo and Juliet, people are able to speak openly to each other as their true identities are hidden beneath their masks. This is evident when Capulet says â€Å"I have seen the say/ That I have worn a visor, and could tell/ A whispering tale in a fair lady’s ear.† This shows that Capulet was able to charm a lady with his stories with the aid of his mask. The word â€Å"whispering† suggests that Capulet’s action was something that had to be done with secrecy and that the mask allowed him to speak openly with the â€Å"fair lady†. Romeo, hidden beneath his mask, is also able to charm Juliet. This is shown when Juliet says â€Å"My only love sprung from my only hate! / Too early seen unknown, and known too late!† The word â€Å"unknown† reinforces the fact that people are anonymous beneath masks and are able to do things they usually wouldn’t. It also shows that Juliet fell in love with Romeo because she did not know his true identity. Also, if Romeo did not wear a mask, he would not have been able to meet Juliet, so the plot would not be able to move forward to reveal their â€Å"death-mark’d love†. During the time in which Romeo and Juliet is set, people often had masked parties as cultural occasions or for celebrations, â€Å"†¦the nuptial of Luciento†¦ and then we masked†. However, in Lord of the Files, masks are used to represent the removal of culture and the dehumanisation of the boys. This is shown in the quote â€Å"The forest near them burst into uproar. Demoniac figures†¦ rushed out howling†¦ stark naked†¦Ã¢â‚¬  This shocks the reader as the boys go from completely civilised children to savages. The word â€Å"uproar† makes it sound as if there is chaos on the island. The word â€Å"demoniac† shows that Jack and the boys have become the embodiment of evil, unlike their former selves. The word â€Å"howling† makes the boys sound more like animals than humans. It may also suggest that the boys have freed their inner beasts and that wearing a mask makes it easier for their inner beasts to come out. The fact that they are â€Å"stark naked† shows that they are not civilised anymore and have become ‘less British’. The boys are also hidden behind masks when they brutally kill Simon and behave like savages. The masks used during Simon’s death protect the boys from punishment as their identities are hidden so no-one can be held accountable. This makes the reader feel upset because Simon gets no justice. Golding may have included this to show that all humans have the potential to become uncivilised and evil, and to show that civility is what contains a person’s inner beast.

Market Oriented Development Strategy for Niger Delta

Market Oriented Development Strategy for Niger Delta ADOPT MARKET-ORIENTED DEVELOPMENT STRATEGY FOR NIGER DELTA DEVELOPMENT. PURPOSE: To provide you with advice on policy strategy for market-oriented development for Niger Delta development and a recommended course of action. BACKGROUND: Conflicts in Niger Delta have generated domestic and international concerns. For more than 20 years, Niger Delta has experienced recurring conflicts often followed by violence which have been inspired, largely, by broad range of economic factors (for example, increased sense of marginalization, exploitation and injustice by the Niger Delta people, and increased poverty and inequality), political factors (for example, long-lasting corruption, mismanagement of allocated resources, and insensitivity of government to the needs and concerns of the Niger Delta people), environmental factors (for example, land degradation and other environmental disasters) and socio-cultural factors (for example, poor value orientation, particularly amongst the youth). Conflicts in Niger Delta have revealed a paradox in the economic development of the region. Niger Delta has remained the driving force of Nigerias oil and gas wealth, having the second highest recognized oil reserves in Africa and being the eight largest oil exporter in the world. Despite the abundance of natural resources, particularly oil and gas, in Niger Delta, and the huge amount of financial resource allocations from the federal government to, and financial investments by oil companies and donor agencies in, the region, Niger Delta has continued to produce disappointing economic development results. There has been a complete disconnection between the level of socio-economic developments in Niger Delta and the amount of financial resources that government, donor agencies, and oil companies operating in Niger Delta have invested in the region. These huge financial resources do not reflect in the living standards of the Niger Delta people; hence they have had insignificant impact on economic development in the region. The paradox in the economic development of Niger Delta has stimulated difficult development challenges, most especially as the conflicts between communities and oil companies, and government, as well as amongst communities, over resource allocations continue to manifest. Though the past governments have adopted many intervention programmes, through various government agencies, which have, indeed, helped to stabilize security situation in the region and created opportunity for economic development engagements, however, the fundamental causes of conflicts have not been tackled. The fundamental causes of conflicts reside in chronic poverty and inequality in Niger Delta. These are still largely deep-rooted in the regions checkered history of marginalization and deprivation, and are connected very much with the continuing forms of instability in the region. ISSUES: The key issue is the paradox in the economic development of Niger Delta. Development results in Niger Delta have been disappointing, despite the abundance of natural resources in the region, and huge amount of financial resources that government, oil companies and donor agencies have invested in the region (See Attachment A in the Appendix). Another issue is the continued difficult development challenges in Niger Delta, for example, administrative oversight, deteriorating socio-economic infrastructures, increasing poverty, inequality and unemployment, declining value orientation amongst young people, and long-lasting conflicts, despite governments interventions. These development challenges have continued to undermine intervention programmes by various government agencies. As a result, the fundamental causes of conflicts in Niger Delta have remained unsolved. These issues have revealed the imperative for a market-oriented economic development strategy. This is particularly important now that the security situation in the region has been stabilized to a large extent. The premise is that for the economic challenges in Niger Delta to be solved, development strategy needs to capture what the Niger Delta people perceive to be their interests, concerns and needs. The precept is that the federal government should focus on providing co-dependent elements of market-oriented development, for example, creating enabling environment for private sector participation in infrastructure development, while the private sector and donor agencies should assist the government in building the capacities of the Niger Delta people and strengthening the policymaking environment. ANALYSIS: Conflicts in Niger Delta have, historically, been framed on resource allocations. In all the conflicts, government has always been blamed for not returning to Niger Delta the proceeds that are derived from the sale of resources produced in the region. In recent years, as part of governments intervention programme to develop the region, government has set up agencies, for example, the Niger Delta Development Commission (in 2000), the Ministry of Niger Delta Affairs (in 2009), the Presidential Amnesty Programme (in 2009), and the Hydrocarbon Pollution Restoration Programme (in 2012). Through these agencies government has channelled funds for the development of the region. Available data shows that between 2010 and 2014, federal government has allocated about NGN7.4 trillion to Niger Delta. This amount came from different sources, for example, statutory oil revenue allocation, federal allocations to Niger Delta states, budgetary allocations to the Federal Ministry of Niger Delta Affairs, Niger Delta Development Commission, Presidential Amnesty Programme, Hydrocarbon Pollution Restoration Programme, and Ecological Fund, Pipeline Security Contracts for the Nigerian National Petroleum Corporation, allocations from the Millennium Development Goals, financial contributions from international oil companies, and financial support from development donors (See Attachments A B). What these mean is that the fundamental problem with the development of Niger Delta is not lack of agencies to implement development plans, or allocation of funds to the region, but managing the funds allocated to the region. The processes for managing the funds allocated to Niger Delta have been deficient in transparency and accountability. The issues with the management of funds allocated to the region speak volumes about the poor governance structures and processes of various development plans. Findings from the reports published by the National Bureau of Statistics and Nigeria Extractive Industries Transparency Initiative between 2010 and 2013 have shown that there is presence of overlap and duplication of projects amongst agencies that are involved in Niger Delta development. The overlap and duplication are as a result of absence of a coherent development plan that is shared by the agencies. This has created inefficiency in project delivery, as resources are unevenly distributed. For example, while many projects are abandoned for lack of funds, other projects are duplicated. Other findings from studies done on states and local governments in the Niger Delta region have shown that there is lack of community engagement in the design and implementation of development programmes, as well as in budgeting processes for infrastructure projects. Many development projects do not include the preferences of the communities; hence the projects are often not tailored to the needs of the people. OPTIONS: There are three options to consider: Option A: Adopt a coherent market-oriented economic development strategy for Niger Delta development. Option B: Review the effectiveness of all the existing development plans that have been developed by various government agencies involved in Niger Delta development, and integrate the relevant initiatives into the strategy in option A. Option C: Recommend to Mr President to mandate all the relevant government agencies involved in Niger Delta development to collaborate and consolidate efforts towards developing the strategy in option A. RATIONALES: The current development plans for Niger Delta do not work for the vast majority of the poor people in the region because of the reasons (and more) stated in the analysis above. Therefore, the region needs a coherent market-oriented economic development strategy that will focus largely on tackling the fundamental issues poverty and inequality. Niger Delta development requires market-based systems that benefit the people, include the people in policy/decision making processes, have efficient governance structures and processes for managing funds allocated to the region, and can be sustained. The proposed strategy is not a new plan, rather an operational instrument, with a unified governance framework that is shared by all agencies involved in Niger Delta development, for implementing the existing development plans. To support Option A, the following cases are made: Case 1: Market systems must be beneficial to the poor: This makes the case that the market systems must be all-inclusive; well-organized; represent the interests of the poor; and sustainable in order to work for the poor. Case 2: Markets are integral part of peoples livelihood: The underlying principle here is that poor people rely largely on the market systems for their means of livelihood. Thus, peoples lives can be improved significantly through functional and sustainable market systems. Case 3: Social inclusion is essential for reducing poverty and closing inequality gap: This presents the case that the key to reducing poverty and closing inequality gap facing Niger Delta is enhancing the opportunities for people to participate in policy/decision making processes. Case 4: Access to the market systems: The guiding principle here is that access to the market systems creates an economic virtuous circle, where peoples standard of living is improved, productivity is enhanced, incomes are increased, food security is strengthened, and hunger and poverty are reduced. FINANCIAL IMPLICATIONS: The activities that will be carried out in respect of Options A and B will be funded from the budgetary allocations of the government agencies that will be involved in the processes. There is enough scope within their budgets to undertake the activities. Option C has no financial implications. RECOMMENDATIONS: The Honourable Minister is graciously invited to: Agree to adopt the strategy proposed in this brief to ensure consolidation of the gains from the stabilized security situation in, and development of, Niger Delta. Note that the proposed strategy is not a new plan, but an operational instrument, with a unified governance framework, for implementing the existing development plans. Agree to direct for a review of all the existing development plans developed for Niger Delta development. Agree to recommend to Mr President to direct all the relevant agencies involved in Niger Delta development to collaborate and consolidate efforts towards developing the proposed strategy.

Mob Involvement With Prohibition :: essays research papers

Mob Involvement with Prohibition In 1917 Congress passed the Eighteenth Amendment to the Constitution which prohibited the export, import, manufacture, sale, and transportation of alcoholic beverages in the United States. This new law is believed to have had the greatest effect on the twenties creating a feeling of rebellion and wild behavior. Many people thought this law violated there right to live by their own standards and have a good time. The Volstead Act passed by Congress set up penalties to all violators of the Eighteenth Amendment. Prohibition is one of the best things ever done by the United States Government. It single-handedly created new business opportunities and brought people together like never before. It had also created a booming new industry, and created a new way of life for many people. Unfortunately, none of these things were good things. The new business opportunities were all in the organized crime realm. With the banning of alcohol they saw an incredible bo om in business. No longer did they have to rely on robbery, brothels and cons. There was a whole new business out there and it was making millions. Prohibition also united the American people more than anything since the World War. Everyone, from the poor to the rich, united to break the law. Even the police, yeah sure they will serve and protect, unless they find a better deal. The police were letting alcohol be made and sold right under their noses. The rich buy the booze to spice up their parties and the poor spend their time and money in bootleggers houses getting drunk. Rarely do the rich and the poor agree on anything. But, prohibition contributed to an increased sense of community and neighborly love. Prohibition also brought big business to the small businessman. Alcohol making used to be done by all the large companies. With prohibition the big companies were put out and the small businesses had to meet the demand. This was what I was referring to earlier by creating a huge business opportunities for the hard-working little guy, rather than the large corporations. I suppose you could venture to say prohibition was like a modern time welfare. By saying this I mean rather than making the rich richer and the poor poorer, prohibition helped the poor lift themselves from poverty without the help of the rich. Also prohibition had many benefits beyond the obvious.

Review of Chart of Accounts †Philippines Essay

Review of Chart of Accounts – Philippines Questions and Suggested Answers 1. In China GAAP, the bonds or stocks purchased are categorized as â€Å"Held-for-trading† or â€Å"Available for sale† or â€Å"Long term investment†, based on the purpose of purchase. Does Philippine GAAP have similar categorization? Philippine client want to separate the marketable securities to current or non-current, it means short or long term, right? Answer: The Philippine Financial Reporting Standards (PFRS) [based from International Financial Reporting Standards (IFRS)] classifies â€Å"Investment in Bonds† and â€Å"Investments in Stocks† as financial assets. For this purpose, investments in bonds or stocks are classified as: ? Trading securities (debt or equity securities) o o ? ? â€Å"Financial assets at fair value through profit or loss† by requirement â€Å"Financial assets at fair value through profit or loss† by designation Available-for-sale securities (debt or equity securities) Held-to-maturity securities (debt securities only) These investments are classified as either current (short-tem) or noncurrent (long-term) assets. The account name â€Å"Long-term investment† is not among the financial assets classification in PFRS. Current investments are investments that are by their very nature are readily realizable and are intended to be held for not more than one year. Debt Trading securities Available-forsale v v Equity v v Current v Noncurrent Current or Noncurrent v – Maybe classified as current or noncurrent depending on whether they are intended to be held within one year or for more than one year v Held-tomaturity v 2 For instance, trading securities are normally classified as current assets because these investments are expected to be realized within twelve (12) of the balance sheet date. Noncurrent financial assets are investments other than current investments. This residual definition means that the noncurrent investments are intended to be held for more than one year or are not expected to be realized within twelve months after the end of the reporting period. Trading Securities or Held-for-trading Securities The first category of financial assets under PAS 39 is called â€Å"financial assets at fair value through profit or loss†. This category includes two types of financial assets, they are: A. Financial assets that are held for trading or popularly known as â€Å"trading securities

Beliefs, Philosophy and Religion

One of the most notable conflicts that have been debated by many scholars since the medieval ages is the controversy regarding the place of philosophy and religion in a society. The two have been used to attack each other in order to uphold their own credibility. The study of Philosophy is directed towards the speculation of the things that govern the world and its processes, and the nature of man and his relationship with other individuals as well as with the world (Gasset, 1964). Philosophy attempts to scrutinize and make rational explication of almost everything that can be grasped by the human mind.Yet, it does not really provide sufficient and concrete answers to all its queries. Religion, on the other hand, focuses its scope on explaining things and phenomena that cannot be explained by science and at some point even those that cannot really be made explicit by philosophy. It tries to give reason for everything that is happening. Its justification for every reason that it provi des is primarily founded on faith (Nasr, 1996). Hence, by faith, it need not be verifiable. A strong faith or believe could suffice one’s doubt and hesitation. However, philosophy would not really admit faith as the justification of something.Reason cannot be supported by merely appealing to one’s faith (Leahy, 2003). Philosophy moves away from dogmatism, which is a character present in religion. Philosophy has a character of skepticism. This means that not unless something is proven to be certain (that which is indubitable or cannot be doubted) philosophy would recognize its validity (Heidegger, 1956). It entails careful and keen analysis of the subject that is being studied. Whereas in religion, it is enough that someone has faith on something in order for it to become valid (Nasr, 1996).These are the most common distinctions that distinguish philosophy from religion. The purpose of this paper is to discuss how philosophy and religion are realized in particular Schoo ls of Thought that influence China namely: Confucianism, Buddhism and Daoism/Taoism. This paper will also compare and contrast these three Schools of Thoughts with Christianity by appealing to their own definitions of Philosophy and Religion. Schools of Thought Confucianism Confucianism is an anthology of ethical values and beliefs that is often equated with religion.These values and beliefs were rooted and developed from the teachings of one of the great thinkers in China, Confucius. His teachings and philosophy were used as the foundations of laws and way of government China and later on in other Asian regions (Chai & Chai, 1973). The teachings of Confucius, like that of Socrates, were neither formally written nor published. Yet his students and disciples made the spread of his teachings. However, according to the Chinese History, most of the recordings of the Confucian teachings were burned up at some point in the Qin Dynasty (Chai & Chai, 1973).Hence, there was a conflict of int erpretation of the Confucian teachings that is evident in various strands of Confucianism. The rebirth of Confucianism was made during the Han Dynasty. It was the motivation for instituting the laws and set of rules of China. Nonetheless, it again faded after the fall of the Han Dynasty wherein Buddhism was introduced to China. Only in the seventh century that Confucianism was revived (Elman, 2002). The chief ideas that the Confucian teachings has were directed toward the ruler, upper class and scholars.Such is a great difference between Confucianism and Buddhism where the latter aims to include the common masses. The instillation of virtues to rulers and noble men is the most original concept in the Confucian teachings. The Golden Rule (Do not do unto others what you do not want others do unto you) is its most celebrated principle that which promotes harmony among all people (Chai & Chai, 1973). With this, Confucianism detests war and the employment of too many laws. Confucianism u pholds its defined five most fundamental relationships which entails varying responsibilities.These relationships include husband and wife, parent and child (filial piety), the elders and the younger ones, ruler and subject, and friendship (Elman, 2002). Among these five, filial piety is the most important relationship that is nevertheless accentuated these days in contemporary China. Lastly, Confucianism puts high regard with the notions of Heaven’s decree, Great Men and Saints, as well as in performing rituals or Li. Buddhism As mentioned earlier, Buddhism’s teachings are directed towards the general populace (Ch'en, 1972).The very concept of Buddhism is founded on the idea of the Enlightenment (wherein Buddha is said to be the Enlightened One). From then on, the goal of Buddhism is to bring man into Perfect Enlightenment or Nirvana (Hanh, 1999). Siddhartha Gautama is the Buddha. He reached nirvana or the enlightenment period through passionate contemplation. Reachin g nirvana would make one free from hunger and selfish desires. It also marks the end of suffering. Once one reaches the enlightenment period, his mind will have everlasting peace (Hanh, 1999). Buddhism advocates the method of truthful inquiry. It tells man not to be overwhelmed by their blind faith.It teaches man to become open-minded and skeptic about the things around him. In accordance with this suggested way of inquiry, Buddhism has established the Four Noble Truths. This tells man that: 1. ) all forms of being, human and other wise are afflicted with suffering, 2. ) the cause of suffering is craving (an illusion of the soul), 3. ) suffering has a lasting end in the experience of nirvana, and 4. ) enlightenment is achieved by a gradual training of the Eightfold Path. These eightfold path is directed towards the clearing of mind and action from indulgence and lustful desires (Ch'en, 1972).Buddhism does not believe in a God or the likes. There is no one that can fully control oneà ¢â‚¬â„¢s own self than him alone. Thus, one has the full responsibility of himself and his actions. And these are not predetermined by a Supreme Being. The concept of Karma is also one of the most distinct features in Buddhism (Ch'en, 1972). It pertains to the belief that all actions have subsequent consequences that are directed to the acting agent. Karma can be a good one or bad one. It depends on the nature of the action performed that produced the consequence that is reflected on the performer of such action.The concept of Rebirth can be best understood by appealing to the principle or doctrine of Karma (Hanh, 1999). Taoism/Daoism Taoism is a school of thought pioneered by Lao Tze or Lao Tzu, also one of the great thinkers in China. Taoism means the path or the way of living to obtain a harmonious relationship with the world and all its definitive processes (Po-Tuan, 2001). Taoism was started as simple philosophical discourse but eventually evolved and took the form of religion. One of its beliefs is the concept of Tao which is defined as the root cause of everything.Tao motivated the rise of the Yin Yang which causes the formation of the universe. Taoism highlights that man should live in harmony with the nature (Po-Tuan, 2001). And only when man achieves such harmony that he will leave in peace and prosperity. Taoism maintains the principle of Wu Wei or non-action which means that man should not go against the nature and must instead go with its operation (Taoist Association of China, 2002). Man need not act since the nature will do the action provided that man lives in harmony with it. Unlike, Buddhism, Taoism believes in multiple Gods.It has hierarchy of Gods that represents system of government in the ancient China (Taoist Association of China, 2002). The ethics defined in Taoism is represented by the three Jewels that which symbolizes compassion, moderation and humility (Po-Tuan, 2001). Taoism encourages the people to examine their way of living by f irst making them realize that living with accordance to nature would mean peace. It also suggests that man should not overly use his being a man. It says that man should prioritize his needs and lessen his wants and desires. Lastly, it orders man not to become egocentric and egotistic.Christianity in China Confucianism, Taoism and Buddhism are the prevailing religions in China. Before the entrance of Buddhism, Confucianism and Taoism are two most notable and most patronized religions in China (Legge, 2004). In fact, the two seemed to be opponents of each other primarily because of their consistent difference on particular viewpoints and issues. But the penetration of Buddhism marks a turning point with regards to the religious inclinations in China. When Buddhism entered China, it signaled the redistribution and reconstruction of religions all throughout China.Confucianism, Taoism and Buddhism have been even combined at particular regions to serve as one religion. Hence, Chinaâ€⠄¢s religion cannot really be said to be concentrated with one of its three most recognized religions (Legge, 2004). In the seventh century A. D. , Christianity was introduced to China (during the Ming Dynasty) (Bays, 1999). Christianity is a very different religion as compared to the earlier religions in China. From then on, Christianity has been said to be the fastest growing religion in China. It is recorded that 40 million to 100 million of population in China are either Catholic or Protestant.This means that China has started to embrace the western religion that is very unlike with their traditional and ancient religions (Bays, 1999). The arrival of Robert Morrison in China has started the spread of Christianity towards China. The Bible has been even translated to Chinese in order to communicate with Chinese people and for them to have easy access to it. Since then, several Christian missionaries have visited and taught the doctrine of the Christian Faith (Bays, 1999). Christia nity The most celebrated feature of Christianity is the fact that it deifies one God. This God is the cause of everything and the director of everything.All man’s action is caused by this all-powerful and all-knowing God. But these descriptions do not suffice the notion of the Christian God. The concept of the Holy Trinity, salvation, and life after death are also included in the doctrine of the Christian Faith (Borg, 2004). The story of Jesus Christ and His death on the Cross is also the highlights of the Christian Faith (Borg, 2004). It represents the martyrdom of the Son of the God in order to save mankind. All in all, the Christian Faith equates all the happening in this world to what God has originally ordained to occur.And no one can interfere nor change what God has decreed. God and Fate or Destiny have been often characterized as the same thing (Borg, 2004). But the former has the most perfect and powerful character. Analysis: Compare and Contrast Confucianism and Chr istianity Among the other school of thoughts (discussed in this paper), Confucianism is the most compatible religion with Christianity. They both advocate that Heaven’s decree is the most fundamental source of order in the world (Chai & Chai, 1973). Only that, in Confucianism, there is no stress given to a god or a deity to be worshipped (Elman, 2002).Such obedience is directed to the Heaven itself. Whereas in Christianity, there is a God that is the end of one’s being obedient (Borg, 2004). As mentioned in the introduction, the defining mark that distinguishes philosophy from religion is the fact that the former repudiates dogmas that tend to confine and limits one’s way of thinking while the latter deliberately suggests and recommends particular doctrines in which one needs not to be certain of (Leahy, 2003). Philosophy speculates and examines the very concept of faith which is often used to justify religions and their established tenets.The belief of the Conf ucianism and the Christianity about the notion of Heaven’s decree obviously falls under the sphere of religion. It is primarily because the existence of such decree from heaven cannot be verified or confirmed yet can be justified through faith. Yet philosophy does not admit such finality. As cited, philosophy is still at the period of examining the very nature of faith as a source of justification of knowledge (Gasset, 1964). With regards to ethical patterns included in the Confucian and Christian faith implies that man should be virtuous in order for him to have a harmonious life.Yet both have different ways of looking at the concept of a harmonious life. For Confucianism, a harmonious life is the achievement of order in human relationships (Chai & Chai, 1973). On the contrary, for Christians, a harmonious life is being free from sins which separate man from God (Borg, 2004). Seemingly Confucian notion of a harmonious life is philosophic in nature which really explains how h armony could be affected by human relationships – that is verifiable and can be validated. Conversely, the Christian notion of a harmonious relationship is really superficial and metaphysical.One cannot really confirm the truthfulness of such statement. And it cannot even be explained by reasoning. But only faith can support it. Hence it is more of a religious belief rather than a philosophic one. Buddhism and Christianity On the other hand, Buddhisma and Christianity is not really compatible with each other (as religions). As discussed above, Christianity advocates a religion that which is primarily directed towards the belief to a God. Yet Buddhism undermines the concept of a Supreme Being that which is all-powerful and all-knowing, and that which controls man’s actions.Buddhism maintains that man can have the full control over his life therefore he does not need a god that would provide guidance and direction for him (Ch'en, 1972). Perfect enlightenment is the stage wherein a man successful reached the point of having a complete understanding of everything including his being (Hanh, 1999). For this reason, God and Buddha is never really equal to each other. Having such distinction, it can be inferred that Buddhism tends to avoid metaphysical speculation since it does not allow the concept of a supernatural entity as cause of man’s actions.Buddhism keeps its teachings to the moral standpoint and its reliance on experiential insight. Whereas, Christianity admits the existence of a God though there is no concrete and material evidence for such existence. The two can be analyzed in the light of a rationalist and an empiricist wherein Buddhism most likely supports the empiricist view of knowledge, that which lies in experience. However, Christianity supports the rationalist’s view that only reason itself even without experience can prove God’s existence. Thus, Buddhism and Christianity is really opposites of one another.Neverth eless, both of them considers codes or doctrines that are needed to achieved their established purpose (Buddhism is for enlightenment; Christianity is for salvation). Hence both suggest dogma that which their disciples must follow in order to achieved their goals. This is where religion is obviously manifested. In the first place, one can go against these codes and doctrines and look for other ways that can also bring the actualization of their goals. Philosophy suggests that one should not limit himself from what is traditionally accepted as true or what is traditionally accpeted the right way of doing something (Heidegger, 1956).Taoism and Christianity Like Buddhism, Taoism is also not compatible with Christianity. There are two major factors that make Taoism and Christianity very different with each other. The first one is that, Chirtianity is a monotheistic religion while Taoism adheres to mulitple gods hence making it a polytheistic religion (Legge, 2004). For Christians, there is only one God (The Holy Trinity is a representation of One God) (Bays, 1999). For Taoists, they have different and particular deities that vary in different regions (in China) (Taoist Association of China, 2002).Secondly, Christians believed that the order in the universe is predetermined and directed by God. On the contrary, Taoists believed that nature is responsible for whatever order the universe has. Such conceptions are significantly and obviously different. There is a semblance of philosophic character that is evident from the two. By appealing to ehtical or moral principles, Taoism suggests that man should live in harmony with nature thus also implying that man should act in accordance with what nature ordained. This appears like the Natural Law Theory.Nonetheless, Christianity upholds the Divine Command Theory which states that man’s action and all the process in the world is ordered and commanded by God or a Divine Entity. Such regard for who or what implies the order of the universe and all its processes can be considered as a philosophical discourse. Yet such is not really explicit in Christianity. On the other hand, Taoism is most likely illustratiing how nature directs and affects the universe and all the things that lie within it including the human persons and their relationship among each other (Po-Tuan, 2001).Conclusion Philosophy and religion are two different spheres. Philosophy does not provide all answers to all the questions that one can give but can provide different ways and approaches on arriving at the possible answers. Religion, in contrast, tends to have answers for all man’s questions that are founded and based on particular doctrines that it has. Yet, it does not give man the chance of verifying the truthfulness of each doctrine by means of other method but faith. Confucianism, Buddhism and Taoism are the most recognize and extensively used religions in China.But after the entrance of Christianity, the Chinese tr aditional culture and relgion have changed significantly due to differences that are distinguishable from the three schools of thoughts and Christianity. The most important note here is the fact that before these schools of thought became religions themselves, they first became philosophical underpinnings which aim to make people realize the obscurity of the world. But eventually they became religions when people started to impose doctrines and rules that are grounded from these teachings in order to live harmoniously with the world.

Radical pesticide from Garongin Essay Essays

Radical pesticide from Garongin Essay Essays Radical pesticide from Garongin Essay Paper Radical pesticide from Garongin Essay Paper Abstraction Spices are merchandises of aromatic workss that grow chiefly in the Torrid Zones. The word â€Å"spices† besides includes merchandise that are more exactly called herbs. aromatic seeds or flavoring blends. Spices like Allium sativum ( Allium sativum ) . ginger ( Zingiber officinale ) . Piper nigrum ( Piper nigrum ) . onion ( Allium cepa ) has been the most common spice in our vicinity. A group of immature research workers were interested to set up a survey on what spices could lend to the day-to-day lives of the people. Their intent is to bring forth extremist pesticide from garongin and happen out if the pesticide produced is comparable to the commercial 1 in footings of efficaciously to kill plagues and a good beginning of an organic pesticide with an low-cost monetary value. particularly to the husbandmans which can barely afford the commercial 1. The research workers prepared all the ingredients that were needed. They chopped the Allium sativum. sliced the onion. minced the ginger. and oppress the Piper nigrum into pulverization signifier. Then the spices were added into a glass of H2O and assorted it exhaustively. Last. the mixture was placed into a pesticide spray container. Garongin pesticide and the commercial one – specifically Malathion – has high quality but they differ in pertinence. The commercial pesticide is expensive. harmful to human. makes the dirt acidic and pollutes the land H2O while Garongin is inexpensive. environmental friendly and non-pollutant. The undertaking itself can be a merchandise of industry and resourcefulness of research workers in happening ways to devour spices and avoids fouling our environment.

The Canadian Economy essays

The Canadian Economy essays With a population of over 30 million Canada is one of the worlds largest and strongest economies. Canada enjoys a desirable standard of living, an excellent infrastructure, a highly educated and skilled labor force as well as a well-deserved reputation as a successful trading nation. Canadas economy has not always been this way. In the late 1980s, right around the 4th quarter of 87 the Canadian economy hit a peak. The economy had just recovered from a trough earlier in the year, but what they didnt realize at the time was that they were heading back down into another trough, which they would eventually bottom out in the 2nd quarter of 91. I chose to look into the Canadian Economy from 1987 to 1994. While examining the chart for Canadas real GDP off Yardeni.com I came to the conclusion that Canadas Economy is strong, it has only hit a negative percent changes twice in the past 20 years. The second negative percent change occurred in the early 90s and that is what I am going to figure out by using some GDP Expenditure Component charts, a retail sales chart, the consumer price index chart, and lastly the interest rates chart. Consumer spending was on the fall, government spending was up and down, real capital spending was declining, and imports far outweighed exports. When consumer spending falls, with it goes the GDP, it puts the multiplier effect into play. When consumer spending changes in a little way, it can have a dramatic effect on everything else. The roll of the government did not seem to have an obvious correlation in the down spiraling economy. Government spending rose nearly 6% during the expansion of 1987 and fell back down almost 4% the following year, but as the economy kept falling, government spending did not change, it was sporadically shifting throughout the following 3 years, until it hit bottom and fell nearly 8% from 91 to 94. Alt...

Digital marketing presents opportunities and challenges to Essay - 2

Digital marketing presents opportunities and challenges to organisations - Essay Example 198). Yet, to obtain the advantages of digital marketing, organisations should add interactive media into their current marketing and business strategies, which is not easy to accomplish. Many companies are having difficulties developing their digital marketing strategies. Studies are being carried out to identify new marketing tools that will contribute to the development and implementation of digital marketing tools. The intention of this discussion is to describe the opportunities and challenges presented by digital marketing to today’s companies by using two concrete examples, Amazon and American Airlines’s SABRE. Various scholars and researchers have identified and described the opportunities and challenges of digital marketing. Digital marketing has created new means or outlets for advertising, selling, and buying. It allows the customer to access an incredible amount of information in an accessible and convenient way. Customers have the chance to look at products and/or services based on their wanted features, such as price, quality, functionality, and others. Customers can use it to get product reviews, or to know about the experiences, opinions, and/or ideas of other users (Urban 2004, 18). Digital marketing has given the end user some control, bringing about an enormous change in marketing processes. By using digital marketing companies can gain competitive advantage through greater customer satisfaction. In addition, digital marketing could be a simple tool for companies since the ‘digital’ feature of marketing allows further technology advances. Because the Internet facil itates two-way communication directly and quickly, implementing digital marketing strategy can occur faster than earlier marketing tools and are at times less costly. The best feature of digital marketing is its ‘instantaneousness’, hence allowing quick response from customers (Morris 2002, p. 205). On the

Language and Power -Task Essay Example | Topics and Well Written Essays - 1500 words

Language and Power -Task - Essay Example such an exploratory analysis, it is the hope of this author that the reader will not only come to a more full and complete comprehension of the material; but will identify with it in a more macro sense – realizing the broader implications that language has on the way that individuals relate with one another and define the world around them. Just as with the process of construction and building, language development and scaffolding is a necessary component in a content area classroom due to the fact that it encourages the individual student to reach beyond themselves and beyond their own comfort levels and integrate with language, idioms, expressions, tasks, and approaches that could be beneficial in helping them to integrate with language and understanding to a more full and complete degree. Through such an approach, the individual is able to develop their own language and communication skills alongside the altered communication style or pattern of the educator/instructor. Many have wrongly asserted that this merely â€Å"dumbs down† the process; however, the fact of the matter is that a variety of different studies have proven the effectiveness upon language development that scaffolding is able to afford. As such, other authors that have been studied have indicated that scaffolding and language development are highly useful tools in the toolbox of those that seek to craft deeper levels of understanding with respect to how language is understood. With that being said, like any tool, authors warn against the fact that instructors must be mindful of the fact that even though scaffolding is useful in helping to develop language skills, it must not be overused and must be utilized alongside other time tested and effective techniques. In such a way, the educator will have the greatest likelihood of experience a positive outcome from using a nuanced approach to education; rather than merely utilizing the same tool to an inappropriate level and being too reliant

Facilities Management Programmes Essay Example | Topics and Well Written Essays - 1000 words

Facilities Management Programmes - Essay Example At the same time, the government has also been committed to the provision of better services in the health, transport, education and other key sectors. In addition, the economies of scale have forced many companies to outsource the services of other companies, and have been observed across the board, for both the private and the public sectors (Wood 2007). The emphasis here of course, has been a need to have growth in such sectors as education, healthcare and utilities. The government too has largely been credited for the outsourcing programmes in the public sector, in a quest to improve and upgrade accommodation, housing and other related services. To this end, the design, finance, build and operate contracting has especially found use in hospitals and schools (CFM 2002). The upgrading and support services provision of outmoded facilities has also not been left out. Given the needs as well as the projected growth of the facilities market in the united kingdom, it is only in order that there be qualified and well trained property managers who will comfortably handle such issue as space design and management, the procurement of facilities, the computation and analysis of facilities costs, as well as the handling of taxation of the same (Chapman 2008). With the rapid rise in technology, and the bar in the ma... rs, it is also important that those managers receives the latest training on computer-aided management of facilities, so as to keep abreast with the dynamic changes in the sector. The onus is on the administrators of the institutions of higher learning in the United Kingdom that offers course if facilities or property management to ensure that their graduates receive training that in s in line with the market requirements (CFM 2002). Otherwise, there is every possibility that they will not only be overtaken by technological changes, but also that they may not impact positively as future property managers. 2. Problem statement The prevailing global credit crunch has especially handed the property market a serious blow. Owing to the numerous losses that these clients may have suffered, there is every need for the industry to ensure that they win back the confidence of the consumers. At the same time, the housing market and the real estate businesses are progressing fast against a backdrop of reducing building space (CFM 2002). This has thus ensured that the property procurement protocols have become more compels by the day. Globalization has also ensured that investors put their money in diversified locations whose property rules differ, and this means that a property managers has to keep abreast with the advances in development of the industry. For this reason, there is a need that the institutions of learning are able to tailor their programmes to suit the need of the market (Nutt & McLennan 2000). Furthermore, clients are becoming sophisticated by the day, while competition in the facilities management demands astute management skills, prompting the industry to seek out shrewd property managers who cab be able to wither the storm (Graham & Price 2000). The

Appraisal Form Assignment Example | Topics and Well Written Essays - 1000 words - 1

Appraisal Form - Assignment Example In general, a simple employee appraisal form can be designed using a combination of checklist, rating scale, and open-ended questions. Using rating scale, the first 5 questions was designed based on the Maslow’s Hierarchy of Needs theory and the ‘ERG’ theory. Question number 6 was designed based on the reinforcement theory whereas question number 7 and 8 was designed using goal-setting theory. Question number 9 was designed using the social cognition theory. Question number 10 was designed based on the motivator factor of Herzberg. Question number 11 was designed using an open-ended question to allow each employee to express what exactly would increase their motivation at work. (See Appendix I –Sample of Employee Appraisal Form on page 6) Basically, question numbers 1 to 9 were purposely designed using the rating scale of 1 to 5. For sure, each employee has their own reason why they have provided a specific rank for each of these first 9 questions. To learn more about why they have provided certain score in each of these nine (9) questions, it is best to make use of an open-ended question. By doing so, the HR manager would know what to do to improve what is currently being provided to each of Softcom’s employees. Question number 1 was designed to determine whether or not the company is providing each employee with the basic needs such as food and water. This question is related to the existence in ERG theory and physiological needs under Maslow’s hierarchy of needs. By asking each employee to rank this statement from 1 to 5, the HR manager can have rough idea on whether or not they are satisfied with what the company is currently providing them. By encouraging each one of them to say something about how the company can improve the available food and water, the HR manager would know exactly what to do and see whether or not the company can do something to make each employee satisfied with

Macroeconomics - Term Paper Essay Example | Topics and Well Written Essays - 1250 words

Macroeconomics - Term Paper - Essay Example In the regulation of the money in circulation, central bank makes adjustments to the interest rate that entails the price of borrowing money. This paper keenly discusses fiscal and monetary policies theories and application. Fiscal policy In their efforts to regulate spending and maintain taxation at an affordable level, governments emulates three types of fiscal policies. The first one is neutral fiscal policy. This type of policy is adopted when the economy is in equilibrium. One of the key aspects of neutral fiscal policy is that all the fund that the government uses to establish projects such as roads, factories, ports among others, is full obtained from tax revenue (Hansen 34). Another type of fiscal policy that government can use to achieve economic development is the expansionary fiscal policy. This entails a situation whereby government spending exceeds tax collected from the residents. This will mean that governments must look for donors to fund them so that they are able to maintain their economy at a competitive level. The policy must be looked keenly to make sure that funds borrowed from the donors are not diverted to other unplanned project .The third policy is contractionary fiscal policy. ... The federal government controls how the money is shared according to the financial year and how they have planned for the budget. The budget must be gone through by the stake holders that include president and the congress. The two bodies must work together so as to come with a comprehensive report that is going to make life bearable to its citizens (Larch and Nogueira 46). The president makes sure that the proposed budget is passed to the congress so that they can decide how much money the government is going to spend on public needs for example, the issue of security is a problem world wide and health care .On the other hand expansionary fiscal policy is commonly used by the federal government to make sure that their business problems are stabilized. Another application area in expansionary policy is the issue of unemployment to its citizens. The unemployed high number of people has to borrow money and return the same money with low interest. In contrast, contractionary fiscal poli cy is mainly used by the central bank or the finance ministry to make sure that the rapid economy growth of a country is put under control. This means that the government must come up with the measures to control it. The government has to increase the interest rates, the central bank then regulates the money their customers are going to deposit and the notes the other bank are going to hold. Monetary policy Monetary policy refers to the process by which the government through central bank regulates the money supply to its citizens with aim of controlling price fluctuations (Heyne et al, 19). This means that the government must make sure that the prices of commodities are stable. The government must still ensure that the interest rates and exchanges rates are guarded fully against

Mans Search for Meaning Essay Example | Topics and Well Written Essays - 1250 words

Mans Search for Meaning - Essay Example This book revealed what human beings are capable of (when) placed under enormous strain and are forced to deal with circumstances most people never have to endure. I believe that under normal circumstances these individuals would have felt that they had certain limitations on their abilities in dealing with difficult circumstances such as these, until they were placed in a situation where their actions depended on their very existence and survival. I found it fascinating that these prisoners had different ways of dealing with their life altering events. They took notice of the beauty of the land around them, they admired the sunset. They gazed at nature as if it were a piece of art.(could you recombine these three sentences into one, better flowing sentence) Humor was another way they would get through their difficult days. The prisoners would often discuss rumors about the military actions taking place. Although these were mostly rumor it gave them hope and a reason for not giving u p. Some of them turned to religion as a way to cope with their difficult days as prisoners. ... These individuals repeatedly beat the prisoners and treated them as inferior in an effort to gain the trust of their captors in return for preferential treatment. They would try anything to help them forget their current circumstances. At one point in the book the author mentioned that the man sleeping next to him was having a nightmare. He thought about attempting to wake him but decided that any nightmare could never be worse than the reality so he let him sleep. This statement was really made me understand the difficulties these men faced on a daily basis. It would have been very easy for many of these prisoners to end their lives and stop the pain, but the desire to survive in hopes that they would be liberated overrode and(is this the word you want) desire to do so. The horrors that these individuals witnessed in a normal society were appalling. It is interesting of how the human mind works and these atrocities actually became an everyday part of life. When individuals died they would take their possessions in an attempt to upgrade their clothing, shoes. (do you think you could clean this paragraph up a little bit) The guards did everything they could to break the spirits of every individual imprisoned in these camps. They did not refer to them by name, only by the numbers tattooed on their bodied and sewn into their clothes. The German soldiers took all possessions away and beat and tortured them in an effort to make them feel sub-human. The soldiers also referred to them as pigs which this was another means of de-humanizing them. The author mentioned the times when they would have to make decisions that may decide your(their) fate. One example was when he had to make a decision to either stay at the camp where he was located or join others

Appraisal Form Assignment Example | Topics and Well Written Essays - 1000 words - 1

Appraisal Form - Assignment Example In general, a simple employee appraisal form can be designed using a combination of checklist, rating scale, and open-ended questions. Using rating scale, the first 5 questions was designed based on the Maslow’s Hierarchy of Needs theory and the ‘ERG’ theory. Question number 6 was designed based on the reinforcement theory whereas question number 7 and 8 was designed using goal-setting theory. Question number 9 was designed using the social cognition theory. Question number 10 was designed based on the motivator factor of Herzberg. Question number 11 was designed using an open-ended question to allow each employee to express what exactly would increase their motivation at work. (See Appendix I –Sample of Employee Appraisal Form on page 6) Basically, question numbers 1 to 9 were purposely designed using the rating scale of 1 to 5. For sure, each employee has their own reason why they have provided a specific rank for each of these first 9 questions. To learn more about why they have provided certain score in each of these nine (9) questions, it is best to make use of an open-ended question. By doing so, the HR manager would know what to do to improve what is currently being provided to each of Softcom’s employees. Question number 1 was designed to determine whether or not the company is providing each employee with the basic needs such as food and water. This question is related to the existence in ERG theory and physiological needs under Maslow’s hierarchy of needs. By asking each employee to rank this statement from 1 to 5, the HR manager can have rough idea on whether or not they are satisfied with what the company is currently providing them. By encouraging each one of them to say something about how the company can improve the available food and water, the HR manager would know exactly what to do and see whether or not the company can do something to make each employee satisfied with

Mans Search for Meaning Essay Example | Topics and Well Written Essays - 1250 words

Mans Search for Meaning - Essay Example This book revealed what human beings are capable of (when) placed under enormous strain and are forced to deal with circumstances most people never have to endure. I believe that under normal circumstances these individuals would have felt that they had certain limitations on their abilities in dealing with difficult circumstances such as these, until they were placed in a situation where their actions depended on their very existence and survival. I found it fascinating that these prisoners had different ways of dealing with their life altering events. They took notice of the beauty of the land around them, they admired the sunset. They gazed at nature as if it were a piece of art.(could you recombine these three sentences into one, better flowing sentence) Humor was another way they would get through their difficult days. The prisoners would often discuss rumors about the military actions taking place. Although these were mostly rumor it gave them hope and a reason for not giving u p. Some of them turned to religion as a way to cope with their difficult days as prisoners. ... These individuals repeatedly beat the prisoners and treated them as inferior in an effort to gain the trust of their captors in return for preferential treatment. They would try anything to help them forget their current circumstances. At one point in the book the author mentioned that the man sleeping next to him was having a nightmare. He thought about attempting to wake him but decided that any nightmare could never be worse than the reality so he let him sleep. This statement was really made me understand the difficulties these men faced on a daily basis. It would have been very easy for many of these prisoners to end their lives and stop the pain, but the desire to survive in hopes that they would be liberated overrode and(is this the word you want) desire to do so. The horrors that these individuals witnessed in a normal society were appalling. It is interesting of how the human mind works and these atrocities actually became an everyday part of life. When individuals died they would take their possessions in an attempt to upgrade their clothing, shoes. (do you think you could clean this paragraph up a little bit) The guards did everything they could to break the spirits of every individual imprisoned in these camps. They did not refer to them by name, only by the numbers tattooed on their bodied and sewn into their clothes. The German soldiers took all possessions away and beat and tortured them in an effort to make them feel sub-human. The soldiers also referred to them as pigs which this was another means of de-humanizing them. The author mentioned the times when they would have to make decisions that may decide your(their) fate. One example was when he had to make a decision to either stay at the camp where he was located or join others

Group Decision Making Essay Example for Free

Group Decision Making Essay Abstract Group decision making is imperative for deciding what action a group should take. This paper aims to define the process of group decision making and examine the discipline, theory, paradigm, and methodology that dominate approaches to group decision-making research. Furthermore, it provides an outline of the research’s perceptual process and endeavors to address an appropriate alternative approach to this research problem, and an evaluation of qualitative and quantitative research designs for this area of research. These are discussed in connection with selected empirical data. Critical Review of Group Decision Making Research Group decision making is one of the most significant and methodological ways of overcoming and/or resolving certain conflicts with the aid of other individuals. It becomes a more controversial in deciding what action a group should take due to the varieties of systems, which are acknowledged in order to solve a particular conflict. Decision making in a certain group is frequently evaluated in a separate manner, as the issue with regard to the process and outcome is concerned. While such a process of group decision making refers to how every member of a group interacts with the others, the outcome is the result of preferred method or action that the entire group has taken. A number of masters from prestigious universities have been arguing with regard to the critical review of group decision-making research since the 19th century. One of the world-renown masters of that time was James Stoner who observed that group decisions are more speculative than the earlier exclusive decisions of the members of a particular group or organization (Stoner, 1961). During the period subsequent to the time when he released his masters’ thesis and scholarly articles concerning the critical review of group decision-making research, numerous researched studies with empirical bases have shown that such a perilous modification is omnipresent or ubiquitous occurrence. Moreover, there is the presence of judiciousness on certain group decisions than the members (Moscovici Zavalloni. 1969; Myers Lamm, 1976). However, the tendency of people to make decisions, which is extreme when they are in a group as opposed to a decision made alone or independently, will take place as a commencing disposition of an individual group members toward a specified way is increased subsequent to the given group decision. For instance, a group of pro-feminist women will be more powerfully pro-feminist subsequent to the given group decision (Myers. 1975). Therefore, on decisions that present to every individual group and/or member, a reasonable disposition in a specified way comes along with a group decision, which belongs to a more reasonable disposition in the same way. Critical Review on a Group Decision Some other conceptualization with regard to the tendency of people to make decisions, which is extreme when they are in a group as opposed to a decision made alone or independently, will be superfluous due the number of outstanding reviews and/or conceptualization until 1970s (Myers Lamm, 1976). Throughout this time, the arguments concerning such a conceptualization have become remarkable. Hence, numerous researchers contributed various ideologies and significant contributions to produce group decisions, which are more speculative than the earlier exclusive decisions of the members of a particular group or organization. In latter years, vehemence for group research with regard to disposition has begun to lessen; it has believed that a thorough retrospective view or survey will contribute to the reorientation of research in such a field. In addition to this view, reassessment will also incorporate the tendency of people to make decisions, which is extreme when they are in a group as opposed to a decision made alone or independently, with other gregarious or communal imaginary and cognitive phenomena. Thus, this research concludes by proposing a few significant matters of desegregation. Moreover, basic cognitive process will be involved in obtaining and storing more knowledge and insights upon demonstrating convincing disputation and communal distinction intervening the doctrine that all natural phenomena are explicable by material causes and mechanical principles within the bounds of group decision making. Study of this consequence shows that subsequent in time of taking part in a discussion group, every member tends to propose greater whereabouts; the demand for more perilous procedures of exploit than individuals who do not take part in any such discourse becomes inevitable. This incident has given birth to the perilous modification of group decision making. Moreover, the tendency of people to make decisions, which is extreme when they are in a group as opposed to a decision made alone or independently, is used in order to explicate and give light to the decision making of a panel or a group of people legally selected to hear a case and to decide what are the facts. Contemporary studies of world-renown scholars and savants show that subsequent in time to meditating into a single group, simulated panel of experts frequently determines retaliatory impairment prior to deliberation. Hence, the studies showed that when the favor of the panel of experts is given to an individual that bears insufficient facts and/or explications with regard to the extant issues, matters of argumentation might lead to a more compassionate outcome. While the panel of experts is influenced to ordain an efficacious or disastrous treatment, such contemporary discourse could yield severe and arduous circumstances to cope with. Progress in Analysis of Group Decision Making Brown’s (1965) innovative discourse of such a perilous modification, one of the vital vindications of selected changes, has been a communal juxtaposition. Based on the entire view of this conceptualization, people are regularly encouraged both to identify and to introduce themselves in a gregarious suitable illumination. To do this, every individual should be constantly preparing knowledge and insights with regard to how other groups of people introduce themselves, and changing his/her personal investiture. Some adaptations of social comparison theory shows that the number of people wishes to be understood as more advantageous than what other groups of people comprehend to be the standard movement. In one case that every individual distinguishes how most other people demonstrate and/or introduce themselves, he or she present him/herself in a reasonable illumination or awareness. Whenever all members of a colluding group involve in the same examination of such a methodological or systematic procedure, the outcome, therefore, is a mean modification in a way of valuable community. There is the presence of two fluctuations of the said temporal arrangement; one is that highlights the displacements of cognitive contents, which have multiple numbers of aspects, while the other one concerns the practice of keeping one jump ahead of a friend or competitor. Based on the studies of such a pluralistic ignorance, every individual or group of people introduces itself and/or its own positions as a settlement of differences in which each side makes concessions in the interval of two different proclivities—the petition to be bound by mutual interests, loyalties, or affections to an individual’s own conception of absolute perfection. In addition to this view, the desire not to be aberrant from the notion of the inner direction of a certain group is also acknowledged. Thus, prior to group discussion review or argument, every member of a particular group trivializes the standards of the group ab initio. Evaluation from the primary valuations of their personal standards becomes distant to some extent or degree. Throughout the argumentations, which are unfolded by the entire group, every individual or member of the group is acknowledged nigh to the right standards; hence, an instance of divergence or disagreement by the common action of how good a group member is and how he or she likes to be ostensible. On delving into the second set of options, a group member directly changes to a more idealistic thought or matter of argumentations. As such, the strategic method of group decision making with most group members is acknowledged. Therefore, the theory concerning pluralistic ignorance is that it prevails for the mere reason of precise exchange of information with regard to the true beliefs of most members of the group in spite of the fact that it might be due to the preconception, which has a basis in or reducible to empirical factual knowledge (Jones Nisbett, 1972). Other evaluators made a thorough explication concerning the possible outcomes of procedures in relation to the social comparison. These evaluations have become a more controversial along the issue concerning such matters of argument in which the group of people are encouraged by an aspiration to be unique from the other groups of people in a more precious and significant way or direction of feelings and/or thoughts (Fromkin, 1970). Moreover, these people are also encouraged to introduce themselves in a more advantageous way than the other groups of people. Briefly, such a group of people desires to be unique and become better than other groups of people. As an analogy, Brown expresses his own feelings by acknowledging the fact that when creating pre-valuations in a certain aspect, every individual member of the group gives him/herself a valuation, which is moderately advantageous than the valuation that he or she takes for granted—the norm or standards the mean group member will share. For a better comprehension with regard to this conceptualization, when a member directly or indirectly deducts the precise standards, he or she then develops his or her personal valuations; hence, making the general options with regard to the perilous modification becomes inevitable to acknowledge. Inasmuch as the technical aspects of making the perilous modification in cognitive contents, which have multiple aspects, the technical aspects concerning a current or fashionable trend is a settlement of differences in which each side makes concessions by the common action of self-enhancement and self-abasement. Indeed, however, it may be quite arduous to acknowledge these two technical aspects theoretically. Nevertheless, there are respective imbrications on the pluralistic ignorance and current or fashionable trends. To support such an argument, the general reference for social comparison comes from presentations that coherent knowledge and insights with regard to the standards of other group members is able to make conformation bias. It takes place when combined or neutral vestige is used to reinforce an already made and intelligibly one-sided point of view. Consequently, every member of the group on both sides may therefore make an action or any movement farther apart, when he or she is presented with the same combined vestige. Such e strategic effect is called ‘mere exposure’ effects in which numerous researched studies have tried creating this terminology for further explication of the denotations of the perilous modification within the group decision making. Processing the Information that Affects the Group Decision Making A number of scholarly studies with regard to the group decision making from different pats of the world have been published; now, it remains one of the global contemporary issues. The original perilous modification research of Stoner (1961) has been globally recognized upon the use of certain outlines of the summary with a dramatic or literary work—the scenario, which shows the value of perils that a group member thinks what action he or she should take. For a better comprehension, it is explained with the best example, which Stoner used. He shows such a perilous modification through playing with a chess—the moves, careers shifts, professional shifts etc. In addition, other studies concern the probability of such a perilous modification. It is showed through the frequent exposure of conditions in which it is more likely to be substantial than any moderate exposure of such conditions; mixed with non-significant. Some studies argue that a certain member’s option or a standard on the matter of argument is methodological function of numerous pro and con debates. It is acknowledged as an individual calls back the memory when hypothesizing his or her personal thought or standards. Therefore, in forming an opinion or estimation of the guilt or innocence of an accused person after careful consideration, a body of citizens sworn to give a true verdict according to the evidence presented in a court of law comes to pre-deliberation decisions in accordance with the respective number and strength of the pro-guilt and pro-innocence statements. Consequently, a formal discourse on a topic or an exposition becomes the cause of an individual’s modification of his or her thought with regard to the running skepticism in the court. During the period subsequent to the time when the conceptualization of the power to induce the taking of a course of action or the embracing of a point of view by means of argument or entreaty is acknowledged, a number of studies distinguish the characteristics of statements, which lead them into being convincing. Moreover, some studies express the denotations of perilous modification. They show this through presenting deputations on the statements within the group members. For a better comprehension concerning this ideology, a specified group may or may not change the way, which has given to it. While every member thinks of producing a good outcome, the arguments take place from the other members of the group. Thus, the function of originality is certainly and specifically determined. However, if such statements or arguments are given from the fact that the individual member is already acquainted with such matter of argumentations, he or she then cannot modify or change his or her position or standards of thinking or sharing his or her thoughts with the other members of the group of choice (Kaplan, 1997). Evaluating Qualitative and Quantitative Research Designs As such, if new convincing arguments are given, but opposing the way that has been pre-approved by the group member, their standards will be modified reversely. Hence, a body of citizens sworn to give a true verdict according to the evidence presented in a court of law who pre-approved one who is justly chargeable with or responsible for a usually grave breach of conduct or a crime will come to regard a more guilty opinion or treat him or her with favor. This occurrence takes place only if he or she is liable to the new statements, which give favor to the fact of having committed a breach of conduct especially violating law and involving a penal. The condition of being peculiar to a particular individual or group, as the issue with regard to the process by which other studies or scholarly researched articles produce, accommodates two general empirical bases. One is that concerns the given correct information. To understand better, such studies or scholarly articles anticipate the methodological system and extent of selecting the thought to be unfolded on the matters of argumentation whether they are breaking up into opposing factions or grouping, or causing to become partially or wholly unbroken up to opposing factions. In addition to this statement or argument with regard to the critical review of group decision making, the number of studies make it easier to bring out the conceptual coordination of mental processes into a normal effective personality or with the individual’s environment, or the operation of finding a function whose differential is known and/or solving a different equation. In view of that fact, the fundamental technical aspect is the same for statements, which have been processed in a more advanced and secure system, or in a mutual or reciprocal action or influence with the other people or group members. Therefore, to support the entire conceptualization of this view, the vestige for the proposition that convincing statements alone may yield choice modification and a position of polarization, which has been assumed for a specific purpose—boldly supported by advanced explications of polarization (Pruitt, 197la. 1971b). Conclusion I have learned substantially from the said research and conceptualization of contemporary argumentations with regard to the critical review of group decision making and it impelled me to seek various means to learn the more advanced and methodological process of critical thinking and evaluation on the group decision-making. First, I have learned to perceive more contemplatively. This means, prior to making decisions or establishing beliefs, a group member must be aware that he or she has personal biases about certain things and he or she should not let this get in the way of arriving at an accurate perception and wise decision. Second, I have learned that by being more involved and by listening to and observing people a particular member of the group, who joins the arguments while discussing the best things to gain favorable outcomes, would be able to gain a broader perspective, if not a holistic view, of people and circumstances as a whole. This means that he or she should not only be satisfied with what he or she sees or wants to see but endeavor to look further and probe deeper into what is actually happening that he or she could not directly sense. Moreover, he or she should also verify his or her perceptions and the conclusions he or she has reached through critical thinking by communicating and learning more about the entities involved. These helpful hints have caused substantial improvement in my critical thinking process relative not only to the office works but to all the other daily activities as well. They have led me to perceive accurately, think critically and gain greater understanding of people and contemporary events. References Brown. R. (1965). Social psychology. New York: Free Press. Fromkin. H. (1970). Effects of experimentally aroused feelings of indistinctiveness upon valuation of scarce and novel experiences. Journal of Personality and Social Psychology. 16. 521-529 Jones, E. E.. Nisbett R. E. (1972). The actor and the observer: Divergent perceptions of the causes of behavior. In E. E. Jones, E. E. Kanouse. H. H. Kelley. R. E. Nisbett, S. Valins. B. Veiner(Eds. ). Attribution. Perceiving the causes of behavior. Morristown. NJ: General Learning Press. Kaplan. M. F. (1977). Discussion polarization effects in a modified jury decision paradigm: Informational influences. Sociomeir): 40, 262-271 Moscovici. S. , Zavalloni. M. (1969). The group as a polarizer of attitudes. Journal of Personality and Social Psychology. 12. I25-135. Myers, D. G. (1975). Discussion-induced attitude polarization. Human Relations, 28, 699-714 Myers. D. G. , Lamm. H. (1975). The polarizing effect of group discussion. American Scientist, 63. 297-303. Pruitl, D. G. (197 la). Choice shifts in group discussion: An introductory review. Journal of Personality and Social Psychology. 20, 339-360. (197lb). Conclusions: Toward an understanding of choice shifts in group discussion. Journal of Personality and Social Psychology. 20. 495-510. Stoner, J. A. F. (1961). A comparison of individual and group decisions involving risk. Unpublished masters thesis. Massachusetts Institute of Technology. Cambridge, MA.

Treating Cystic Fibrosis with Gene Therapy

Treating Cystic Fibrosis with Gene Therapy In this dissertation we shall consider the field of gene therapy in specific relation to cystic fibrosis.   We examine the different delivery vector mechanisms that have already been explored and concentrate primarily on the adeno-associated vectors. We examine the current state of research and consider the advantages and drawbacks of the various methods considered. We conclude with a discussion and analysis of our findings and   make anumber of assumptions relating to the future direction of the researchin the field.   The rate of progress in the field of gene therapy has been enormous. We must remind ourselves that the first clinical gene transfer experiment took place in 1989 when a patient with malignant melanoma received genetically modified auto logous T cells. (Rosenberg SA et al1990) Gene therapy encompasses two major areas. The in vivo field, where genes are incorporated into the target cells of the living body and the ex-vivo field where the target cells themselves are genetically modified outside the body and then re-implanted. Medical science has been using the basic techniques of gene transfer for a long time. The technique has been exploited when viral genes are introduced to human cells when a viral vaccine is administered. The key technologies that allowed the transition from vaccination to gene therapy were the evolution of methods that allowed the genes to be isolated and replicated (cloned) and manipulated (engineered) prior to transfer into human cells (Freeman SM et al 1996) The key principle in this process is the efficient transfer of the manipulated therapeutic genes into the nuclei of target cells usually be means of various vectors. This dissertation will be considering the utilisation of these vectors in some detail. In broad terms, the new or modified genetic material is able to produce new proteins which can restore deficient or abnormal functions of genetically diseased tissues, to generate tissues that have entirely new properties or to create transplantable tissues for the controlled release of therapeutic proteins. (Russell SJ  1997) In terms of viral vectors, prior to 1996 science was dependent on the use of modified retroviral vectors (eg.MMLV) to effect gene transfer into the chromosomes of a target cell and the adenovirus vectors when such integration was not needed. Neither vector was particularly successful as the intact nuclear membrane (in then on-dividing state) was a major barrier for chromosomal gene integration. (Sikorski R et al 1998). A breakthrough came with the realisation that lentiviruses (e.g. HIV) have the same ability to transfer genetic coding into the cellular genome but could do this in the non-dividing or dormant phase cells. (Amado R G et al 1999) In vitro, lentiviruses have been shown to change the target cell’s expression of proteins for up to six months. importantly, they can be used for terminally differentiated cells such as respiratory epithelium. The only cells that the lentivirus cannot penetrate the nucleus are those in the quiescent (G0) state as this blocks the reverse transcription stages of protein synthesis. (Amado R G et al1999) Cystic fibrosis Cystic fibrosis is the most commonly lethal inherited recessive inthe caucasian population. It affects about 1 per 2,500 livebirths. Thetreatment of cystic fibrosis has improved enormously in the last fiftyyears with the life expectancy increasing from an average 10 years to30-40 years now. The prime cause of death in affected individuals is the repeatedcycle of infection, inflammation and fibrosis of the respiratory tractwhich eventually culminates in respiratory failure and death. The disease itself is caused   by mutations in the single gene forthe cystic fibrosis transmembrane conductance regulator (CFTR) whichproduces a protein found in sweat and pancreatic ducts, gut,seminiferous tubules, lungs and many other tissues. The mutationsresult in an abnormal protein which, when expressed in the lungs,produces thick viscous and dehydrated secretions. This does not allow for the efficient expulsion of bacterial pathogensfrom the lungs and a number of highly resistant forms of bacteria arecommonly found in cystic fibrosis (viz pseudomonas aeruginosa)(Porteous DJ et al 1997). An individual must receive a defective copy of the cystic fibrosisgene from each parent in order to develop the clinical picture ofcystic fibrosis. Following normal genetic principles, if two carriersconceive a child, there is a 25% chance that it will have cysticfibrosis, a 50% chance that it will be a carrier and a 25% chance thatit will have two normal cystic fibrosis genes. Viral and non viral vectors Viruses have an ability to enter a host cell and combine their owngenetic material with that of the host cell. This is the basicrationale behind the science of gene transfer therapy.   As we shalldiscuss in some detail in this dissertation, there are a number ofpotential viral vectors that have been explored, evaluated andexploited in the search for an efficient and safe form of therapy.Viruses are not the only vector that can be utilised . Simply placingDNA in the nasal mucosa will produce some incorporation into theepithelial cells (Knowles MR et al 1998). This â€Å"absorption† can bedemonstrably enhanced further by the combination of the DNA withvarious plasmid or lipid complexes(Zabner et al 1997) The advantages of lipid or plasmid assisted transfer mechanisms arethat they do not appear to generate the immunological responses thatare seen with the viral vectors. They can also be used to facilitatethe transport of much larger pieces of DNA which would otherwise belimited by the packaging consideration incumbent on the viral vectors.(Felgner P 1997). The use of retroviral vectors is far from straightforward. The heavilypublicised case in April 2000 brought some of the problems to theattention of the media. A retroviral manipulation of   a case of X-SCID(X linked severe combined immunodeficiency) was treated by gene therapywith an apparent degree of success (BBC 2002). This particular diseaseprocess is caused by a mutation on the gene which codes for the C chainof the cytokine receptors which is situated on the X chromosome andvital for the functional development of T Killer lymphocytes which aretherefore completely absent in the condition A multinational team used a retroviral vector to insert a functionalcopy of the gene into bone marrow stem cells which were thenre-transfused back into the patient. (Cavazzana-Calvo M et al 2000).This particular case resulted in a return to normal levels of T cellsin a comparatively short period of time. This was hailed in both thepopular media and the peer reviewed journals as a major success and itcan indeed be considered a landmark as it pioneered the successful useof an ex-vivo procedure that avoided direct in vivo transfer of thevector. The reason for specifically highlighting this particular case isthat following the initial optimism of the clinical team, two of thefirst ten patients with this condition who were treated in the same waysubsequently developed a leukaemia-like illness. Genetic analysis ofthe malignant cells suggested that the retroviral vector used in thetransfer had also activated an oncogene LIM-only2 (LMO2) which is knownto be associated with some forms of leukaemia. The clinicians reviewingthe situation felt that, although it was not the only cause of themalignancy it was one of the events that triggered it. Similar concernshave been raised in respect of other clinical trials. (Lehrman S 1999) The prime reason for presenting these events is to demonstrate thefact that there is both a theoretical and practical risk of insertionalmutagenesis. Reduction of the risk requires greater specificity of thetargeting of the genetic deficit   perhaps by directing the expressionof the therapeutic genes to various specific tissues utilising bothtransductional and transcriptional targeting. Relph K et al 2004), In terms of specific considerations of the arguments in favour of theuse of retroviral   vectors, one can cite the fact that they have ahighly efficient mechanism of gene transfer together with lowimmunogenicity. It is a well researched and well studied system and isknown to selectively infect actively dividing cells. The conversearguments reflect their disadvantages including their ability todisturb or activate oncogenes, the fact that they are difficulty tospecifically target and it is difficult to obtain high titres in theclinical situation (after Olsen, J. C. 1998). In broad terms, the principles behind the use of retroviral vectorsare that they must be modified in order not to be able to transmit anyovertly pathological coding. This involves the deletion of viral helpergenes such as gag, pol and env   to render the replication processinvalid. This is done by utilisation of a producer or packaging cellline. (Nichols, E. K 1998). An example of a commonly utilised and extensively researched vector isthe MoMuLV. It is an engineered vector which can store 8 kb of RNAwithout compromising packaging efficiency. It is a hybrid cell lineeasily grown in mouse fibroblast cells There is a subdivision of the retroviral vectors known as thelentivirus, which is the only retroviral vector capable of integratinginto the chromosomes of non-dividing cells. This has been effectivelydemonstrated in vitro (Naldini L et al 1996).    The biggest problem with the lentivirus vectors is that theyappeared to only produce very low titres. Some recent researchsuggested that a modification to a amphotropic envelope protien wascapable of allowing higher titre levels. (Rolls M et al 1999) At about the same time that the scientific press was learning aboutthe problems with retroviral transfer (see above) other investigatorswere working with adeno-associated viruses (AAVs). A similar processwas invoked using adeno-associated viruses to correct a genetic defectinvolving coagulation factor IX. The adeno-associated viruses were usedas they were considered to be amongst the safest candidates for genetransfer. They do not naturally cause disease processes in humans andhave only rarely been found to incorporate in a random fashion into thehuman genome. Although it is noted that adenoviruses do cause oncogeneactivation in rodents although it has not been found in humans(Blacklow NR 1988).   The trial had a very positive outcome. (Kay MA et al 2000), but thetrial author (in later research work) published a study which suggestedthat, in study mice, the vector used in the trials actually integrateditself into gene containing regions of DNA more frequently that it didinto non-coding regions (Kay MA et al 2003). The findings were reportedas the fact that new genetic material was randomly distributed amongstall of the chromosomes particularly at sites of gene activity. On thisbasis, there appears to be at least a theoretical basis for thepossibility of similar cellular defects such as occurred in the X-SCIDpatients. Adenoviruses are comparatively simple structures. They arecategorised as double stranded DNA viruses. They have icosahedralcapsids with twelve vertices and seven surface proteins. The virionitself is spherical and non-enveloped and in the region of 70-90 nm insize. Their natural history is that they are spread easily in the naturalstate by the faeco-oral route and also by respiratory inhalation whichclearly has great implications for the treatment of cystic fibrosis. A theoretical analysis would immediately suggest that the adenovirus should be a suitable candidate for gene therapy as they can codefor specific proteins and they do not produce infection pathogenicviral offspring.    The early trials into this particular area were reviewed by Griesenbach(Griesenbach U et al 2002) who pointed out that the cystic fibrosisgene was first cloned in 1989 and in the subsequent   years, 18different trials were carried out, all with rather low degrees ofsuccess. They collectively trialed three different vectors, namelyadenoviruses, adeno-associated viruses 2 and cationic liposomes, andalmost universally found that each vector had a very low rate ofclinically significant gene transfer and none was sufficient to achieveclinical benefit    Plasmid Complexes At its most basic level, a plasmid is a small accessory collection ofDNA which is found in the cytoplasm outside of the nucleus. They arecapable of independent replication and can be manipulated with rathermore ease than nuclear DNA. Early investigations into the field of gene transfer explored thepossibility of plasmid vectors   and demonstrated the feasibility of themethod to effect CFTR gene transfer in vitro (Alton EW 1993). Otherteams had demonstrated the fact that, in clinical use theplasmid-liposome is both nontoxic and non-immunogenic (Hyde,SC et al1993).   This appeared to raise the possibility that many of theimmunological problems encountered by teams working with viral mediatedgene transfer mechanisms might be circumvented. In vivo work (Yoshimura,K et al. 1992) had demonstrated that genescould be transferred into the cytoplasm by this method and Stribling, R(et al 1992) demonstrated that, once there, they would then replicatenormally. Alton experimented with a CFTR-plasmid preparation in miceand demonstrated that it was capable of correcting the chloride levelsin cystic fibrosis mice back to normal levels (Alton EW 1993) Although the initial results were encouraging, clinical trials weredisappointing as the plasmid complex could not easily penetrate thethick mucous residues in the diseased lungs of patients with cysticfibrosis. (Erickson,R 1993) The plasmids typically have a positively charged head-group which isable to bind to the DNA strand and a hydrophobic tail group whichfacilitates the transfer of the complex across the cellular membranes.Initial studies suggest that   between 100-1000 times more DNA isrequired to effect successful gene transfer when this method iscompared to viral vectors. (Santis,G et al 1994). One alternative adaptation has been reported by Stern M (et al 2003)who points out that one of the solution of delivery is to ensure thatthe respiratory epithelium is exposed to the DNA over a long period.Their solution was to encapsulate the CFTR-plasmid in a slow releasebiocompatible polymer. Clinical trials are underway but not yetreported. The adeno-associated vectors appear to have (at least on atheoretical basis) a number of advantages over the vectors that we havealready discussed. They are based on a virus vector that is alreadynon-pathogenic (Berns, KI et al 1995) and has a mechanism that allowsit to be a long-term persistent entity in human cells (Blacklow, NR etal 1989). The adeno-associated vectors are particularly useful indealing with disease process that involve single gene mutations. This,therefore   makes it particularly suitable for single gene disorderssuch as cystic fibrosis and alpha 1 antitrypsin deficiency. (Flotte, TRet al 1998). In addition, some workers have also developed vectors which are capableof   producing either inducible or constitutive expression of thecytokine, interlukin-10   (IL-10) which is an importantanti-inflammatory protein which, on a theoretical basis, could beuseful not only in cystic fibrosis   but in other disease process whichhave chronic inflammation as their prime manifestation (viz Type Idiabetes mellitus or inflammatory bowel disease) (Egan, M et al 1992).These manifestations have been studied and have now reached the stageof early clinical trials (Wagner J et al 2002). With specific reference to the implications of cystic fibrosis, wecan point to trials which have resulted in the expression of cysticfibrosis transmembrane conductance regulator (CFTR) from rAAV(recombinant adeno-associated vectors) in cell cultures (Flotte, TR etal 1993), in animal models (primates) (Afione, SA et al 1996), andagain in early phase I clinical trials (Wagner, J et al 1998) The rAAV-IL-10 model has been studied in bronchial cell culturesfrom cystic fibrosis patients, to determine the functional consequencesof CFTR complementation. This has not yet been demonstrated in vivowith humans but in both mice (Song, S et al 1998), and monkeys (Conrad,CK et al 1996) The overall results of these (and other) studies have shown that   itis possible to achieve long term gene transfer and functionalexpression of the replaced gene (some studies for as long as 18 months)without any overt pathological findings. The histological findings are something of a surprise however, as,at least in both primate and mouse studies, the vector-introduced DNAin this form does not appear to be assimilated into the geneticmaterial of the chromosome, but persists in log strings or concatemersthat are episomal, which is in complete contrast to what happens whenthe naturally occurring agent infects the cell. There is some evidenceto suggest that host cell intrinsic factors such as DNA-dependentprotein kinase play some role in this process (Song, S 2001). The significance of this finding could be that the exclusion of thefunctional, newly introduced DNA from the rest of the nuclear gene poolmay be less likely to produce effects that could be either potentiallydisruptive to the host cell and less likely to activate oncogenes.Phase I trials have demonstrated significant rises of CFTR levels inboth sinus and lung tissue with no evidence of vector-related toxicity.(Wagner, JA et al 1999)   The adeno-associated vectors are constructed from proviraladeno-associated vectors plasmids, which have the Rep and Cap proteinsdeleted and substituting the appropriate gene (CFTR or equivalent)between the rAAV2 inverted terminal repeats together with other signalsequences such as promoter and polyadenylation sequences (Flotte, TR etal 1994) The packaging processes allows for about 5 kb of rAAV genomes to becarried   in the vectors which are prepared using a cotransfectiontechnique utilising human embryonic kidney cells (HEK-293) where thevector plasmid is cotransfected into the cells with helper agents(plasmid pDG) being used to encode the rAAV2-rep and -cap genestogether with the adenovirus helper functions (Grimm, D et al 1998).These are incubated for between 48 and 72 hrs. The cells are then lysedand the resultant agents are then separated by ultracentrifugationagainst a density gradient and affinity chromatography (Zolotukhin, Set al 1999).   The vectors are thereby amenable to being separated by both theirphysical characteristics and also their biological characteristics(infectious units). They are carefully screened to ensure the absenceof any possible contamination from non-modified (replication competentAAVs) prior to clinical usage. (Muzyczka N 1994) The comparatively small â€Å"payload† of the adeno-associated vectorsis proving to be a significant problem. The vector itself is small whencompared to the comparatively large size of the CFTR gene. (Flotte TRet al 1993) It does not leave any room to manoeuvre to manipulate thevector-specific sequences in the way that we have described with theretroviral and adenoviral groups. (Flotte TR et al 2001). A number of authors have characterised the problem with theobservation that the rAAV is typically about 20 nm across which allowspackaging of about 4.7 kb (kilobases) of transferable modified gene(exogenous DNA). (Dong JY et al 1996), If   it is combined with otherenhancers such as the promoter, the polyadenylation signal, thisclearly reduces the capacity for the DNA component. (Duan D et al2000). The Yan paper (Yan Z et al 2000) has outlined a novelexploitation of the unique ability of the rAAV genomes to link togetherin strings which appears to have the ability to bypass this particularlimitation.( Flotte TR 2000). The mechanism itself is the capacity of two distinct rAAV genomes thathappen to simultaneously infect the same target cell to undergo anintermolecular recombination insider the transduced nucleus of thetarget cell. This was a chance finding which arose from work involvingrAAV-derived episomes (Kearns WG et al 1996) in primate airways. It wasfound that some of these episomes were configured as circular head totail concatemers (Duan D et al 1999). This could have been either froma â€Å"rolling circle† replication from a single vector or alternatively,from an intermolecular recombination of material from multiple cellularpenetrations which combined within the palindromic inverted terminalrepeat sequences that are an intrinsic part of the AAV genomestructure. The authors were of the opinion that it was likely to be thelatter eventuality (Duan D et al 1998) It was a logical progression to try to exploit this phenomenon andthereby bypass the limitations imposed by the relatively smallpackaging capacity of rAAV. The adeno-associated vectors capsid onlyhas a capacity of about 5 kb. If we consider that the 145 nucleotidestretch of the AAV-ITR (inverted terminal repeat) sequence has to be inplace at both ends of the single-strand DNA for the vector DNA to beboth replicated and packaged, this only leaves in the region of 4.7 kbof genetically active material in each rAAV particle. As we have cited earlier in relation to the Dong paper (Dong JY et al1996) the CFTR gene accounts for about 4.5 kb which leaves very littlespace for other enhancing material. Because of this, the actual CFTRvector that has been used in the clinical trials to date uses only theminimal promoter activity of the AAVs-ITR itself to actually activateand drive the CFTR expression (Flotte TR et al. 1993). To look at this potentially important development in a little moredetail we can consider Duan’s original paper (et al 2000) and theauthors describe what they call a â€Å"superenhancer†. They describe acombination of a potent simian virus (SV40) and CMV immediate earlyenhancer elements as being packaged in one rAAV vector and a luciferasegene assisted by a small minima;l promoter in another rAAV vector. Invitro experiments suggested that either the SV40 or the intrinsicpromoter activity of the AAV-ITR was sufficient for this purpose. Theintermolecular recombination described above, was found to occur inboth vitro and in vivo experiments and was found to be sufficient tohave a greater than additive effect. Initial results from these varying methods are encouraging insofaras they are producing results of transgene expression which are 100-600times greater than with the unenhanced vector alone. (Yan, Z et al2000) Although not directly referable to our considerations of cysticfibrosis, we should note that Yan’s group and other workers have doneexperimental work which has culminated in the long term expression offunctional levels of erythropoetin with this two vector method in micein vivo. (Naffakh N et al 1995), This basic principle has been further enhanced by Sun (Sun L et al2000) with an ingenious manipulation of the system. They triedinserting the promoter and the first half of the coding sequence in onerAAV vector, immediately followed by a splice donor and then theupstream half of an intron. In the other rAAV vector was the downstreamhalf of the intron, the splice acceptor, the second half of the geneand the polyadenylation signal. To quote the author verbatim: This strategy is efficient enough to mediate high-level expressionand the intermolecular junctions are apparently stable enough tomediate expression for several months in vivo. Although this is clearly an ingenious augmentation of the sameprinciple , we should note that there are both advantages anddisadvantages to both pathways. The strategy that adopts the superenhancer takes its strengths fromthe fact that the recombination mechanisms optimise theposition-independent and orientation-independent functions of theenhancers.   Consideration of the options would suggest that there arefour potential recombination outcomes from the process described.Either of the two vectors could be on the 5’ end of the heterodimericmolecule and clearly either molecule could be in either orientation. With the superenhancer option, all four of these possibleintermolecular recombination outcomes should be functional fortransgene expression whereas if compared to the split intron strategy,by using the same reasoning, it is clear that only one out of the fourcould work. On the other side of the argument, the superenhancer option has thedisadvantage that the actual coding sequence of the gene to betransferred must still fall within the packaging capacity of the vectoritself whereas the split intron allows for a greater functionalexpansion of the packaging capacity. (after Flotte TR et al 2000)   In either event it can be seen that these ingenious modificationseffectively eliminate the main size limitation of the rAAV deliverysystem. Although initial pre-clinical work is encouraging it appearsthat there is still some potential for a degree of immune responseparticularly if the host organism has not experienced the newlyproduced protein before. A number of studies have been done on animal (vertebrate andprimate) with only minimal success. Different administration methodshave been studied including direct administration into the lung (WagnerJ et al 1999), IM injection (Song, S et al 2001 B) and hepatic portalvein infusion (Song, S et al 2001 A)       Human clinical trials have taken place with these vectors (Flotte T etal 1996)(Wagner J et al 1998) (Virella-Lowell, I et al 2000). Thestudies were done on adult male and female patients (18-47 yrs) whowere pseudomonas free and had recently been hospitalised for IVantibiotic infusions The disappointing results were probably a reflection of the factthat the CFTR defect is also interconnected in some way with   aproinflammatory phenotype which appears to be triggered by the abnormalprotein via an unfolded protein response. The authors were able to showevidence that the rAAV-CFTR mechanism was able to   correct the proteinproduction defect, they found it clinically difficult to transduce asufficient number of cells in the airway to reverse the inflammatoryresponse. It is proposed to run further experimental work which combines the  CFTR expression with an anti inflammatory   gene such as the IL-10.There is some in vitro work to suggest that this may be a possibleworkable approach (Teramoto, S et al 1998). Other work on ways ofenhancing the phenotypic expression of the modified genotype hassuggested that the use of various promoters and the rAAV-CMV/beta-actinhybrid promoter (CB-AAT) was found to be tone of the most efficient, atleast when it was compared to the other tested options such as the CMV,E1, U1a and U1b promoter constructs (Teramoto, S et al 1998) Overall, the initial results appear to be encouraging. A singleinjection of an rAAV-CB-AAT vector in animal studies has resulted inhigh level, stable transgene expression which has persisted over thelife span of the experimental animals and that there was no detectableinflammatory response in the animals who had received this form oftreatment (Flotte TR 2002) Flotte (et al 2002) reports that four human clinical trials at bothPhase I and Phase II level are currently underway examining the effectsof the rAAV-CFTR vector. They had an entry cohort of seven patientswith the vector being applied to the nasal lining, the maxillary sinusand the bronchus. The authors report no adverse effects being found andthat they have observed transgene expression at doses of 6 x 108 drp inthe sinus or 1 x 1013 drp in the lung. There are no reported interimfindings from the Phase II trials as yet.    There is clearly a potential for clinical benefit on the basis of theresults found to date if one can extrapolate from in vitro and animalexperiments. The authors comment that, in contrast to the adenovirusvectors there is a marked lack of inflammatory toxicity with the rAAVvectors. Despite these positive comments, we should not, however, overlook thepotential limitations of this particular delivery system. These havebeen identified by various authors as:    The inhibitory effect of preexisting airway inflammation on rAAV transduction in the lungs (Virella-Lowell, I et al 2000) A relative paucity of receptors on the apical surface of airway epithelial cells (Summerford, C et al 1998), The relatively weak nature of the minimal promoters used in the first-generation rAAV-CFTR vectors(Flotte, TR et al 1993), The potential for adverse long-term effects from rAAV vector DNA persistence. (Wu, P et al 2000) The Flotte group are currently investigating this problem by examiningthe hypothesis that the barriers in the airways of the cystic fibrosissufferer are primarily   due to the neutrophil-derived -defensins (HNP1and HNP2) and are actually reversible by the mechanism of AAT proteindelivery (Virella-Lowell, I 2000) Wu and his co-workers have been looking at ways of manipulating thegenetic make up of the rAAV2 capsid and thereby trying to enhance thetargeting ability so that the vector specifically targets the serpinenzyme complex receptor on IB3–1 cells – which is virtually specificfor the Cystic fibrosis bronchial cells Zabner, J (et al 2000), have considered alternative rAAV serotypesin the hope of finding one that will bind more specifically to thebronchial cells Other peripheral adjuncts have also been explored includingpromoters to enhance the effects of complementation and superenhancerswhich have been shown to improve the ability of the rAAV toconcatermerise with the help of smaller amounts of promoter agents  (Duan, D et al 2000). Perhaps it is appropriate to conclude this section on considerationof adeno-associated vectors with a critical analysis of a very recentmulticentre, double-blind, placebo-controlled trial (Moss RB et al2004) This was a well constructed, fully statistically significant anddouble blinded trial which considered   both the safety and thetolerability of repeated doses of adeno-associated serotype 2 vectorrepeatedly given by aerosol inhalation. The vector contained â€Å"cysticfibrosis transmembrane conductance regulator (CFTR) complementary DNA(cDNA) [tgAAVCF], an adeno-associated virus (AAV) vector encoding thecomplete human CFTR cDNA.† The entry cohort was comparatively small with 42 patients, of whom20 received the active agent. A number of indices of airway functionwere measured. Of particular interest to our considerations in thisdissertation was the fact that   vector shedding was found in alltreated subjects up to 90 days after inoculation. And that all subjectswho received the active agent exhibited at least a fourfold increase inthe serum AAV2 neutralising antibody levels. Of the 20 treated patients, six subsequently underwent bronchoscopy.Of those six, gene transfer but not gene expression was demonstrated inall of them. On this basis, it would appear that the actual transfermechanism is effective, but there are other factors present whichappear to interfere with the subsequent expression of the gene in termsof protein production. The study did not comment on the possiblereasons for this. The authors were able to conclude that the delivery system workedwell with no evidence of adverse effects and that treated patientsdemonstrated an â€Å"encouraging trend in improvement in pulmonary functionin patients with CF and mild lung disease.† Lipid 67 We have discussed the various shortcomings of the virus-associatedvectors and this has prompted researchers to explore and consider otheroptimising options for facilitating gene transfer. Zabner (J et al1997) considered the use of cationic lipids in this process and foundone   GL-67:DOPE (colloquially known as lipid 67) which appeared to beparticularly helpful in the process. Cationic lipids appear to show a degree of promise as possible vectorsfor CFTR cDNA transfer into respiratory epithelial cells