The social and bio medical model

The social and bio medical model The bio-medical and social models of health offer different views of health and disease. Outline the main characteristics of each model and assess their strengths and weakness in explaining health and disease. Health can be viewed as the state of being fit and well, as well as a state of mental sanity (WHO 2005). According to Blaxter (2004), if a person can perform daily functions such as going to work, taking care of the household, etc he/she is healthy. Many studies have found that lay people define health as the absence of illness (Williams 1983, Calnan 1987, Hughner Kleine 2004). However being healthy means different things to different people as much have been said and written about peoples varying concepts of health. Some lay perceptions are based on pragmatism where health is regarded as a relative phenomenon, experienced and evaluated according to what an individual finds reasonable to expect, given their age, medical condition and social status. For them being healthy, may just mean not having a health problem, which interferes with their everyday lives (Bury 2005). Some taxonomies have evolved in attempt to define health. In this work, health has been considered from the perspective of biomedical and social models. According to Baggott (2004) the biomedical model of health looks at individual physical functioning and describes bad health as the presence of disease and illness symptoms as a result of physical cause such as injury or infections and attempts to ignore social and psychological factors. Baggott (2004) states that the features of biomedical model rest mainly on biomedical changes, which can be defined, measured and isolated. In effect this is directed towards the dysfunction of the organs and tissues of the body rather than the overall condition of the patient. Biomedical treatments often involve the removal of the cause, for instance the virus or bacteria. The biomedical model is based on the belief that there is always a cure and the idea that illness is temporary, episodic and a physical condition. The basic values of the biomedical model of health consist of the theory called doctrine of specific aetiology, which is the idea that all disease is caused by theoretically identifiable agents such as germs, bacteria or parasites (Naidoo Wills 2004). The advantage of biomedical model shows disease as representing a major public health problem facing our society. This model sees disease state as an issue that needs to be treated, and that disease can be readily diagnosed and quantified (Ewles Simnett 2003 2010). This approach appears narrow, negative and reductionist. In an extreme case, it implies that people with disabilities are unhealthy and that health is only about the absence of morbidity. Further, this model is limited in its approach by its omission of a time dimension. Modern biomedicine rests upon two major developments, both of which remain influential to this day. It is first important to consider the Cartesian revolution after the seventh century French philosophy Rene Descarts. The Cartesian revolution encouraged the idea that the body and mind are independent or not closely related (NRC 1985). In this mechanistic view, the body is perceived to function like a machine with its various parts individually treatable, and those that treat them considered engineers (Naidoo Wills 2004). Biomedical also concentrates on the individual unlike the social model. Biological model adopts a negative perspective on health as it views health more in terms of the absence of disease than the possession of healthy attributes (Baggott 2004). This model stresses the importance of advancing technology both in the diagnosis and treatment of disease, an approach that has undoubtedly improved both the knowledge and understanding of numerous diseases. Biomedical model has led to the improvements in the treatment of patients, which has favoured gains both in the length and quality of life of people. Despite the aforementioned feats, the biomedical model has received considerable criticism, as many writers have argued that it was inappropriate to modern, complex health problems (Inglis 1981). The medical model, in terms of specific health risks, does not encompass all of what health means to an individual. For instance, a physician speculating on what, based on current knowledge at the time, would be the composite picture of an individual with a low risk of developing coronary artery disease. Further criticisms of this theory focused principally on the suggestion that it over simplified biological processes now known to be very intricate. For many diseases there are multiple and interacting causes. Moreover, such a theory looks only to the agent of disease, and ignores the host, and the possibilities of biological adaptation. The theory is much more easily applicable to acute conditions than to chronic ill-health and is difficult to apply to mental disorders. The second theory of the biomedical model is called the assumption of generic disease. This is when each disease has its own distinguishing features that are universal, at least within the human species. These will be the same in different cultures and at different times, unless the disease-producing agent itself changes. Criticisms of this focus on the rather obvious point that diseases are differently defined in different cultures and that medical definitions of disease have clearly changed over time. Each new advance in knowledge of physiology and each new wave of technology have added new definitions of ill health to the accepted canon. Despite the doctrine of specific aetiology many conditions, which are still only symptoms or syndromes, are recognized within medicine as diseases. Generally, it can be seen that what is viewed as illness in any particular society and at any historical time depends on cultural norms and social values (Naidoo Wills 2004). Thus new diagnoses such as alcohol, post-traumatic stress disorder, chronic fatigue syndromes are born through an interaction of new knowledge about both their possible causes and how they might possibly be helped. As a definition of disease what doctors treat has obvious problems, however, it implies that no one can be ill until recognised as such and leaves the concept at the mercy of idiosyncratic individual medical decisions. The third theory is the scientific biomedicine, which accepts the model of all ill-health as deviation from the normal especially the normal range of measurable biological variables. There is an association with the definition of health as equilibrium and disease as a disturbance of the bodys function, with the purpose of medical technology the restoration to equilibrium. The immune or endocrine, or neuropsychological systems attempt to restore the normal and the purpose of medicine is to instigate or assist this process. But medical science now realizes that the human organism has no set pattern for structure and function, and it is often unclear where normal variation ends and abnormality begins. The fourth theory of medical model is based on the principles of scientific neutrality. Medicine adopts not only the rational method of science but also its values objectivity and neutrality on the part of the observer, and the view of the human organism as simply the product of biological processes over which the individuals themselves have little control. The reply to this is that the practice of medicine, whatever its theory, is always deeply embedded in the larger society. It cannot be neutral, for there are wider social, political and cultural forces dictating how it does its work and how the unhealthy are dealt with. Biomedicine now admits multiple and interactive causes, and that the whole may be more than simply the sum of the parts. Social and psychological causes of ill health- stress, unhappiness, life events- are admitted as agents of disease or contributing factors, but they are not themselves defined as ill health. Modern medicine has moved on, to incorporate elaborate ideas about the various and interrelated causes of ill health. Studies of the way in which doctors make diagnoses demonstrate this, while at the same time lip service is paid to the importance of the social. Moreover, even when social and psychological influences are admitted this is still a very negatively oriented approach to health. The social model came about in mid twentieth century when there was increasing dissatisfaction with the dominant model of health offered by biomedicine. The preoccupation with disease and illness made it less able to deal with any positive concept of health. The ideology, which viewed the individual in mechanistic ways justified ever-increasing use of medical technologies, precluding the exercise of other therapies and diminishing the importance attached to positive health or preventive medicine. Since the last decade medical professional practice has become a major threat to health. Depression, infection, disability and other specific estrogenic disease now cause more suffering than all accidents from traffic or industry by transforming pain, illness and death from a personal challenge into a technical problem, medical practice expropriates the potential of people to deal with their human condition in an autonomous way and becomes the sources of a new kind of un-health. The emphasis on health as simply the absence of disease encouraged thinking about only two categories the health and the disease. As we are meant to believe that science can produce a utopia of disease free and lengthy life meaning scientists only look for their magic bullet. There is a feeling that the most angry critiques of the biomedical model was wilfully ignoring the contributions of modern science to human welfare. But claims to the unique truth of biomedicine were weakened by some loss of faith in sci entific objectivity and a distrust of a Frankenstein technology that could run out of control, and this was part of the modern movement towards a new model usually called social health. Social model of health imbibes social constructs and relativity in its approach to health. It tends to define and redefine health in a continuous manner, and views health differently between individuals, groups, times and cultures. Some supporters of Social model have written extensively about sickness having a role to play in various societies (Parsons 1951) as this helps to determine the structure of and functionality of the society. The concept of social health incorporates many differences of emphasis though it has to be noted that it is more than simply the recognition that social factors such as poverty have to be included in a model of the causes of ill health. The social model is a different construction, locating biological processes within their social contexts and considering the person as a whole rather than a series of distinct bodily systems. The social model is organic and holistic rather than reductionist mechanical method. A mechanical system acts according to its programming, its instructions, or natural laws. The social model allows for mental as well as physical health and wider sphere of taking part in active life. This model also allows for more subtle discrimination of individuals who succeed in leading productive lives in spite of a physical impairment. Another disadvantage of this model is that the conception runs the risk of excessive breadth and of incorporating all of life. Thus they do not distinguish clearly between the state of being healthy the consequences of being healthy nor do they distinguish between health and the determinants of health (Ewles Simnett 2010). The medical profession is a social institution, which cannot be separated from the values, pressures and influences of the society in which it practices. As health has been defined in various ways, most part rests on the ideas of the normal and of seeing health as opposed to disease or illness. In practice, the definition of health has always been the territory of those who define its opposite: healers, or practitioners of medicine as a science or a body of practical knowledge. Since medicine is one of societys major systems, it is obvious that it is these definitions which will be institutionalised and embodied in law and administration, though the extent to which lay models adds to or diverge from this body of ideas is significant to the individual in respect of their perception of health. Whilst the medical model built on the Cartesian theory of the body as a machine disorders can be corrected by repairing or replacing parts of the organism, holism describes the view that the whole cannot be explained simply by the sum of the parts, just as healthiness cannot be explained by a list of risk factors. Every disturbance in a system involves the whole system. Human beings are living networks formed by cognitive processes, values, and purposive intentions, not simply interacting components (Blaxter 2004). The development of this social model has been accompanied among the public, by a growing enthusiasm for alternative therapies, which tend to rest on holistic theories. Gradually, these too have been integrated to some extent into the mainstream model. In order to have a comprehensive understanding of health, one has to look at the phenomenon from various premise of health definition, as just one aspect may not provide complete answer to the enquiry about our health at a particular given time. It is therefore important to consider the various aspects of health when making judgement and decision about the health status of an individual. In summary, the biomedical model of health is obviously most easily defined by the absence of disease, though the model is also compatible with more positive definitions in terms of equilibrium of normal functioning. In the social model health is a positive state of wholeness and well being associated with but not entirely explained by the absence of disease, illness or physical and mental impairment. The concepts of health and ill-health are unbalanced. The absence of disease may be part of health but health is more than the absence of disease.

Sociology Essay -- Sociology Essays

The social growth of the young in different classes A Youth in Poverty   Ã‚  Ã‚  Ã‚  Ã‚  To most, it’s very easy to imagine how it would feel to grow up without much of anything in life. Hell...I can tell you first hand what it feels like to not have a decent pair of shoes or pants without holes in them, or old â€Å"hand-me-down† toys while most of the kids you know have â€Å"state-of-the-art† toys. To many children in this kind of situation, it seems like a very bleak world to live in. No child should ever have to experience this kind of life. However, due to ignorant parents and an even more jacked-up government, there are many children that will always be in this predicament.   Ã‚  Ã‚  Ã‚  Ã‚  Now, it would be hard to think of any good coming out of living in such conditions. But just like a many things in this so-called existence, a person would have to look very hard to find the good things. There are, in fact, good things about living in the pits of poverty. For instance, children that are poor tend to appreciate things much more than a child with a more â€Å"privileged† life. When they get new things, they treat those things like intricately wrought gold, or a fine work of art. To them, a brand-new pair of ‘Jordan’ gym shoes or a ’PS2’ seems like pure treasure. Over time, this quality of appreciation will develop continually over the years. They will make responsible choices on things that they will always appreciate. With hope and a prayer, they will be able to pass down this quality to their future generations.   Ã‚  Ã‚  Ã‚  Ã‚  Another good quality that poor children have is their ability to socialize. When you are poor, you have little room to fear embarrassment. If you’re embarrassed about meeting new people or talking in front of a crowd, they you may as well be embarrassed with everything else in you life of poverty. Being poor is humiliating enough....being scared to talk is nothing compared to that. A kid that has just about nothing in life will hope to make as many new friends as they possibly can. Possibly so that they can fill in the little void they are likely to grow out of having so little. They are very assertive, and will do anything for attention. Jokes, stories, comments, and the sacred art of â€Å"Blazing† or â€Å"Baking† are the tools that poor children will use for socialization.   Ã‚  Ã‚  Ã‚  &n... ... many times I wanted to knock a rich kid’s teeth into his brains.....((Ahem...)) They think that since they are rich, they are better that the entire world. When they think this, I wish nothing more than to strangle them with a garden hose and beat them with a wet towel....((Ahem, ahem...)) Everyone it this world should know...that even though they live life on a silver platter, they should remember one thing; when silver is not taken care of properly, it can and will tarnish over time. They may think that they are better than the world, but they will mess their lives up with that arrogant attitude. They can lose friends, family ties, relationships with other loved ones, jobs, schools, and other things of importance. No one is better than the world...no matter how much money they may have, they are only human. Conclusion Time: The â€Å"glorious† life ain’t all that it’s cracked up to be. Because when a person wakes up from the fantasy of having everything they want, they are able to realize that money is nothing more than paper with a dead man’s face on it. The youth should know that there is more to life than wealth. Look hard, and they will be able to find what I’m talking about.

Dams :: essays research papers

Many people have already dammed a small stream using sticks and mud by the time they become adults. Humans have used dams since early civilization, because four-thousand years ago they became aware that floods and droughts affected their well-being and so they began to build dams to protect themselves from these effects.1 The basic principles of dams still apply today as they did before; a dam must prevent water from being passed. Since then, people have been continuing to build and perfect these structures, not knowing the full intensity of their side effects. The hindering effects of dams on humans and their environment heavily outweigh the beneficial ones. The paragraphs below will prove that the construction and presence of dams always has and will continue to leave devastating effects on the environment around them. Firstly, to understand the thesis people must know what dams are. A dam is a barrier built across a water course to hold back or control water flow. Dams are classified as either storage, diversion or detention. As you could probably notice from it's name, storage dams are created to collect or hold water for periods of time when there is a surplus supply. The water is then used when there is a lack of supply. For example many small dams impound water in the spring, for use in the summer dry months. Storage dams also supply a water supply, or an improved habitat for fish and wildlife; they may store water for hydroelectricity as well.2 A diversion dam is a generation of a commonly constructed dam which is built to provide sufficient water pressure for pushing water into ditches, canals or other systems. These dams, which are normally shorter than storage dams are used for irrigation developments and for diversion the of water from a stream to a reservoir. Diversion dams are mainly built to lessen the effects of floods and to trap sediment.3 Overflow dams are designed to carry water which flow over thier crests, because of this they must be made of materials which do not erode. Non- overflow dams are built not to be overtopped, and they may include earth or rock in their body. Often, two types of these dams are combined to form a composite structure consisting of for example an overflow concrete gravity dam, the water that overflows into dikes of earthfill construction.4 A dam's primary function is to trap water for irrigation. Dams help to decrease the severity of droughts, increase agricultural production, and create new lands for agricultural use. Farmland, however, has it's price; river bottomlands flooded, defacing the fertility of the soil. This agricultural land may also result in a loss of natural artifacts. Recently in Tasmania where has been pressure

Discuss the Difficulties in Seeking to Adopt a Common Social Policy

Assignment 2-Take Home Exam (Question 3, 5 and 6) Question 3 Discuss the difficulties in seeking to adopt a common social policy and social welfare agenda among the E. U. member states. Introduction A social policy is a public policy and practice in the areas of health care, human services, criminal justice, education, and labor. (Malcolm Wiener Centre) In European Union, it has passed a long way to seeking adopt a common social policy and social welfare agenda among the E. U. member states. Caune et al has summarized the process of social policy into three steps followed by the milestone of EU.First stage was to create a common market and keep the national welfare policies. During the first stage E. U. did seek to establish a certain policy, such as freedom of movement for workers and freedom of establishment and equal pay and rights for migrant workers. The second stages was Maastricht treaty that creating Maastricht criteria as new economic policy regime and established ‘sof t law management’. The thirds stage was focus onwards coordination and competition of national welfare policies. The treaty of Lisbon which is the recently moment in E.U. social policy, it defines E. U. seeks to assess the significance of the poverty/social inclusion open method of co-ordination in terms of what it indicates about the EU’s engagement with social policy. From the historically, EU was did a lot of works to creating social policy and social welfare agenda. But E. U. still faces many difficult to making a common social policy among E. U. states. Furthermore, this essay will mainly discuss on the difficult in seeking to adopt a common social policy and social welfare agenda among the E. U. ember states which are based understand and analyzed the history and concept of E. U. social policy. Discussion From the three stages of form a social welfare system, we could found European Union has really well social welfare systems as an example for the rest of the wo rld. It has maintained social equality among EU members which defend weaker market participants and guarantee them acceptable standards of living. However, EU is now face great challenges, such as rapid growth in EU expansion and integration, growing competition among member states for investments.Most of them are now becoming difficult to a adopt a further common social policy EU, such as increasing about personal expectancy, population migration process, growing income inequality and the existing social exclusion. These difficulties are mainly coming from two sources which are national and European level. If EU aims to form a common social policy, they will firstly facing a problem of different social policies pursued by member states. Rutkauskiene indicated that there is† no unanimous opinion about all existing social policy in EU. (Rutkauskiene, 2009) Every member states have their social policy depends on different typology, such as Mediterranean model and antipodean mode l. These different social policy models in the place which lead EU faces a huge challenge-too many different social policy model in the members will hinder the process of adopt a common social policy in EU. One of the objectives of common social policy is maintain social equality among EU member state but each member state has a different economic situation that leading to different budget on social welfare expenditure.Hence, there will be conflict between different countries investment on the social welfare. One of the example are from the EU integration process, employee are free to move to a low cost countries and also employee from poor countries can move to a member state that has a better work condition. The enlargement or integration of European has becoming one of the difficulties in order to adopt a common social policy in EU because it has direct on the social issues, such as unemployment rate and fair work rights.Traser describe enlargement had already, in 2004, caused pu blic anxiety about large numbers of low-skilled and semiskilled workers from the new Member States seeking both employment and benefits in the EU-15, and displacing national workers with cheap labour. (Traser, 2005) The issues about free movement of employee is only one example about the differences of economic situation between member states but it can be a main difficulties for EU to adopt a common social policy because the members state are only stand for their own country and competing with other member states.In the European level, EU are also did a lot of work trying to leading member states participate on the process of adopt a common social policy but it is difficult as well. Since the Maastricht Treaty a concept of ‘soft law’ management measures are used to implementation of the EU activates. This has given to the control measures that are based on voluntarism, education and the sharing of best practices. (Rutkauskiene, 2009) In other world, member’s sta te is voluntary participation in an exchange of information or action.The European council collected all these soft measurement 2000 in Lisbon and give them a name of ‘Open Method of Coordination. (OMC)† (European Council Web) In the European council website explained OMC- set goals are monitored and supervised, best practices are shared and there is a scope to share. (European Council Web) But there are one important feature of the OMC is that goals and achievement are established at the EU level, while the measure and practice to achieving them are left for national governments. Many scholar are debate the disadvantage of this method.OMC is the lack of obligation to implement any agreements, and the lack of sanctions for failing to meet any obligations (Szyszczak, 2006). In other words, EU did not give in to any suggestion about policy to national government, and national government did not need to adequately orient their active measures according to OMC goals. Moreove r, each member states can present their own conclusions on the certain policy areas in their national actions plans, such as pension and health care area. Rutkauskiene has found a greatest number of faults in pension’s area caused by OMC. Rutkauskiene, 2009) Everyone is too different in their personal needs and clamming to adequate for all is not feasible. So a government policy should be set a minimum pension sum to be guaranteed and set of this agreement among EU member states. In other worlds, it is necessary that guidelines for changes in indicator evaluation are set, thereby blocking the way for different understanding about social affairs. From the different argument on OMC policy we can it was mainly established a principle of turning into coordination among EU member state but it facing difficulties turning this policy into an operational manner.Vandenbroucke state the post challenge of Lisbon treaty is EU need an operational social policy. (Vandenbroucke, 2002) Unfor tunately, according to the discussion that the current OMC policy has some disadvantaged that made difficulties for EU to adopt a common social policy. Conclusions This essay has started with an introduction milestone of adopt the EU social policy. The difficulties in adopt a common social policy among EU member states have been compounded furthermore by the fact that large number of state in EU and each of them implementing a different social programs and social policy measures.Then we look on how European Union to dealing with this difficulties of great variety in the social policy systems. We have been chooses the current model to coordinate of social affairs in 2000 at the signing of Lisbon strategy which are Open Method of Coordination. Based on the analysed from different academic literature, â€Å"the main shortcomings of the OMC were identified as the lack of obligation and no sanctions for failing to carry out the activities set out in the agreements reached. (Rutkauskiene , 2009) Hence, the inefficiency of current policy is other main difficulties in adopt a common social policy. At the end, the process of adopt a common social will be forward in the future and the difficulties are also coming continuously at different stages. Reference Arnaudova, F. Z. L. A. A. (2011). Growth, well-being and social policy in Euroep: trade-off orsynergy. European Social Policy Centre Concuil, E. , from http://ec. europa. eu/invest-in research/coordination/coordination01_en. htm Daly, M. (2006). EU Social Policy after Lisbon.Queen's Univeristy, Belfast. Malcolm Wiener Center for Social Policy. Retrieved 10 Jan 2013, from http://www. hks. harvard. edu/centers/wiener Palier, P. R. G. a. S. J. a. B. (2011). The EU and the Domestic Politics of Welfare State Reforms. England. Rutkauskiene, L. (2009). Problems in the formation of the common EU social policy: Vilnius Univeristy. Szyszczak, E. (2006). Experimental Governance: The Opend Method of Coordination. European Law Jou rnal. Traser, J. (2005). Report on the free movement of workers in EU-25: who's afarid of EU enlargment? Brussels:European Citizen Action services. Vandenbroucke, F. (2002). The EU and Social Protection: What should the Euroepan Convention Propose. Retrieved from http://econstor. eu/bitstream/10419/44291/1/644397675. pdf Vobruba, G. Debate on the enlargement of the Euroepan Union. University of Leipzig. Question 5 the single market is the fundamental economic underpinning of the EU. Discuss why  this single market is problematic in the EU with regards to the digital technology sector Introduction The Europe commission in a 1985 white paper launched the single market programme.The main purpose of single market is ‘seeks to guarantee the free movement of goods, capital, services, and people – the EU's â€Å"four freedoms† – within the EU's 27 member states. †(European Commission Web) It was launched as the fundamental economic integration of the EU. It creates large benefit to the enterprise and EU-citizens. The European commission and the EU’s executive arm, has target ‘energy, digital and transport sectors as priorities for depending market integration. †(Egen) In relating to the digital technology sector, the world economic is now more deepening on the digital technology.A 2010 study commissioned by the European Policy Centre from Copenhagen Economics showed that an integrated European Digital Single Market (DSM) would lead to an increase in GDP of at least 4%, with concrete benefits for consumers and citizens. (Economics, 2010) European commissions have already been set in motion about importance of digital single market. For example, Monti report had already highlighted the importance of developing the digital single market, which was also reflected in the digital agenda and the single market act.However, there are still many problem existed in the EU with regards to the digital technology sector. This e ssay will outline of the reasons of why this single market is problematic in digital sector, which are mainly because of less enforce on inappropriate regulation in the member states and cost effectiveness and differences in provision of the infrastructure and ‘old national monopolists’. Discussion In Pablo’s report, which has summaries the European commission need to work more on to build trust and confidence in digital single market.Echeverria has indicated that â€Å"European Commission need to stresses that the consumer rights directive marked an important step forward in terms of increasing legal certainty for consumers and businesses in online transactions, and today constitutes the main consumer protection instrument for online services. † (Echeverria) A single market strategy will require a higher level of legal regulations in regarding to issues such as cybercrime, data privacy and spam while ensuring free movement and the possibility of transacti ons on the internet.Otherwise this single market will be a problematic in digital sector because of the existence of a patchwork of different legal provisions and barely interoperable standards and practices. Also the consumer can’t access the full benefits from this strategy if this regulation is poor. European commission’s report of building the digital single market has identified more and more pollution is using the digital technology now. (Commission, 2011) Peoples are now using more internet service to making a convenience life, such as the online cross border trade.Moreover the digital single market will allow citizens to have access throughout the EU to all forms of digital content and services. So in order to creating single market digital sector, if people are not use digital service in a safety environment then there will be a data protection problems. The other reasons of why  this single market is problematic in the EU with regards to the digital technol ogy sector, which is cost effectiveness. In Zuleeg’s report has determine that a single digital market will require large scale investments in fixed and mobile networks, with much of this investment needing to come from private operators. Zuleeg, 2012) Especially in the European finical crisis period, Europe government and private operator will need to have spent more to support this investment by developing new investment vehicles and guarantees. Michelle Egan also defines a digital single market is a long way of investment and still have many barriers now. (Egan) But the single market in digital sector will improve productivity and contribute to increasing Europe’s medium to long term competiveness. It also brings out benefit beyond the economic which it can help some societal problem, such as fragmented labor market and environment problems.According to all of this facts, we can finding the single market can bring large benefit to citizens and social but it will nee d to put extra investment by government and private operator. So this single market will bring out a conflict between internal users and external stakeholders because of cost effectiveness. A study by Copenhagen economic has list out â€Å"there is a range of national and international operators, totalling close to 100 mobile operators. â€Å"(Copenhagen economic) In the Australia digital sector there are mainly one operator provide the most mobile and internet infrastructure which are Telstra.The digital sector is fragmented in European compared with other countries. The most of the digital companies are competing on a national scale instated of across borders. None have continent-wide operations and provide difference in provisions of infrastructure. One of the example is there are still less operator can provide mobile service across borders and also with a high roaming fees. However the single market strategy in digital sector is trying to integrate these companies into one gr oup.This single market strategy may become problematic in the digital technology sector because a fragmented supplier industry may hamper certain developments. From the overall finding, we can operator is the main stakeholder with a large impact on the digital sector. The study by Copenhagen has further explained this fact as â€Å"a lack of market consolidation with ‘old national monopolies’ keeping their strong position in local markets due to government protection in the past. â€Å" The operators are stress on their profit and ignore the importance of single market.One of the major benefits of European single market is increasing competition, leading to lower prices and better welfare for consumers and society as a whole. But the operator has main power in the national market and can refuse price convergence. Conclusion At the end, the single market in digital will have large impact on European economy either in public sector or employee or consumers or producer s ides. But according to the nature of digital technology sector which is fragmented industry and investment barriers so the single market has being a problematic in this industry.Reference Completing the internal market White paper from European Commission to European Council (1985). Brussels. Commission, E. (2011). Building the digital single market-cross border demand for content services. Echeverria, P. A. On completing the digital single market Economics, C. (2010). The conomic impact of a european digital single market. Egen, M. Twenty years after the completion of the EU's single market programme, member states have still not eliminate all barriers to trade. London: The london school of economic and politcal science. Zuleeg, F. (2012).A digital single market by 2015. eSharp. European Mobile Indsutry Obeservatory. (2011) Monti, M. (2010). A new strategy for the single market. â€Å"The Single Market†. Europa web portal. http://ec. europa. eu/internal_market/index_en. htm. Retrieved 03 January 2012. Question 6 what are the problems to be encountered in forming a European sense of identity among the citizenry of the EU? Introduction A sense of a national identity is â€Å"the person's identity and sense of belonging to one state or to one nation, a feeling one shares with a group of people, regardless of one's citizenship status. (Smith, 1993) Usually, these are nation-states but it also can implied an entity group of European Union. McCormick writes sense of European identity as â€Å"a related term of Europeanism refers to the assertion that the people of Europe have a distinctive set of political, economic and social norms and values that are slowly diminishing and replacing existing national or state-based norms and values. †(McCormick, 2010) Johan Borneman indicates the practices of Europeanization in term of languages, money, tourism and sex and sport. Borneman 1997) European Union are getting practice on this through the creation of the European single market, the expanded the European Union from twelve members in 1985 to twenty-seven members in 2007 and link the legislative and policy frameworks of EU with European identity. As we explained before EU has a long history of this integration process but there are still many problems encountered in forming a European sense of identity among the citizenry of the EU. There are especially in some countries are having this problems such as British.Moreover, this essay will discuss on the main problems that are in forming a European sense of identity among the citizenry of the EU. It also will consider some examples in English. Discussion Medrano has summarized the main problems into three section which are â€Å". 1) conflated behaviour in referenda on reform treaties of the European Union, support for European integration, and identification with Europe, 2) conflated different dimensions of European identity, and 3) failed to unpack the various meanings that citizens a ttach to the idea of identification with Europe† (Medrano, 2010)In the detail, the first problems are mainly concerned on the public debate on European identity. Many people see no opportunity to influence supranational decisions effectively because there are lacks of intermediary actor primary covering European issues. In the public, the media or journalists are both have lack of supporting on EU news. Vreese said â€Å"It is difficult to ‘sell’ an EU story. † (Vreese, 2004) Medrano has asked many journalists do you agree you play an important role in ‘crating a European identify’. (Medrano, 2010) The most of them unanimously agreed that the answer should be ‘NO’.Some journalists believe their role is to create engagement and interest and not to influence identity. One of the examples is in British, the public opinion is divided and the country is becoming the most of skeptic members in EU with regards to EU policy of common curre ncy and the enlargement. There is other problem influencing public opinion about Europe, such as difference in social-demographic characteristics. Most of researcher has find men being more supportive of Euro-pan integration and higher levels of education are associated with being more positive towards the EU.The second problems listed by Medrano, can be described as there are having many dimensions of European identity either by national or citizen. If there are too many dimensions of European identity that will results a lack of precision use in the use of the sense of European identity. The official dimensions of European identity is a precondition for a democratically legitimise European Union with feeling of belonging together of the people living in the member states, including the awareness and the support of common values, achievements and aims.But in related to a real case the European identity is far lagging behind national identity. Fukuyama has given one example of Franc es created a strong national identity by built around the French languages. (Fukuyama, 2012) In order to compared within the EU’s dimension, EU are more stress on political and policy identity but the nation’s dimensions are more focus on culture and social level. EU has 27 members within different culture and religion. These countries have already built on different level of national identity.EU is now trying to integrate this national identity into one common identity which is European identity. So EU needs to conflate different dimension of European identity. The third problems is failed to consider the citizen’s ideal about European identity. The EU defines concept of European identity are most physically based, such as free movement of goods and service. But the officials should to promote a sense of belonging to Europe citizens emotionally. Medrano stated there are lacks of identification with Europe among citizens are mostly interested in the emotional di mension of identification. (Medrano,2010)Besides of Medrano’s measured three problems, there are still many other problems in order to create a sense of European identity. One of these problems are EU has less use any knowledge or instruments of identity policy to deliver the sense of European identity, such as education. Walkenhorst writes â€Å"without a sense of commitment and knowledge of citizenship rights the European peoples cannot establish a democratic identity in the sense of supporting the EU as a legitimate political system†. (Walkenhorst, 2004) EU also will not being able to demonstrate its benefits for the European citizen without using an instrument of identity policy.For instance, provide more education or program on spread the sense of European identity will also help to avoid the problems of different religions. EU has different religions identity, such as Christian and Muslim. The concept of European identity need to consider the ideal of multicultur alism and democracy. Conclusions This essay draws an analysis of the problems encountered in forming a sense of European identity which are based on an understanding what is a sense of European identity and how could generate a sense of identity.Since the firstly forming a European Union, EU are trying to creating a sense of European identity. A sense of national or regional identity is an emotionally feeling belongs to a group. EU did a lot of work that letting people are physically feeling of European citizen, such as free movement of people and goods. One of the examples, are Eurostar given people are more mobility in traveling around European. However, EU is now facing problems on ignored the citizen’s emotionally feeling of European identity and conflicts of different dimension about European concept of identity.Each member state and citizens has different dimension about European identity. The best way to solve this problem is using accurate instrument to spread the ide al of European identity, such as education and media. But the fact is there is lack of use media and education that results a problems in forming a sense of European identity. Reference Adrian Favell, E. R. , Theresa Kuhn, Janne Solgaard Jensen and Juliane Klein. (2011). The Europeanisation of Everyday Life: Cross-Border practices and Transantional Identitifcations Among the Eu and Third-Country Citizens. Foweler, J. B. a. N. (1997).Europeanization. Annual Review. Retrieved from http://www. jstor. org/stable/2952532 . Fukuyama, F. (2012). European Identities Retrieved from http://blogs. the-american-interest. com/fukuyama/2012/01/10/european-identities-part-i/ Margaret R, A. (2008). Perceptions of European Identity among EU Citizens: An Empirical Study. McCormick, J. (2010). Europeanism: Oxford University Press. Medrano, J. D. (2010). Unpackiing European Identity: CAIRN, INFO. Smith, A. D. (1993). National identity: Univeristy of Nevada Press. Versteegh, M. L. C. (2010). European Ci tizenship as a New Concept for Euroepan Identity.

Phylogenetic

Molecular Phylogenetics An introduction to computational methods and tools for analyzing evolutionary relationships Karen Dowell Math 500 Fall 2008 Molecular Phylogenetics Karen Dowell 1 Abstract Molecular phylogenetics applies a combination of molecular and statistical techniques to infer evolutionary relationships among organisms or genes.This review paper provides a general introduction to phylogenetics and phylogenetic trees, describes some of the most common computational methods used to infer phylogenetic information from molecular data, and provides an overview of some of the many different online tools available for phylogenetic analysis. In addition, several phylogenetic case studies are summarized to illustrate how researchers in different biological disciplines are applying molecular phylogenetics in their work. Introduction to Molecular PhylogeneticsThe similarity of biological functions and molecular mechanisms in living organisms strongly suggests that species descended from a common ancestor. Molecular phylogenetics uses the structure and function of molecules and how they change over time to infer these evolutionary relationships. This branch of study emerged in the early 20th century but didn’t begin in earnest until the 1960s, with the advent of protein sequencing, PCR, electrophoresis, and other molecular biology techniques.Over the past 30 years, as computers have become more powerful and more generally accessible, and computer algorithms more sophisticated, researchers have been able to tackle the immensely complicated stochastic and probabilistic problems that define evolution at the molecular level more effectively. Within past decade, this field has been further reenergized and redefined as whole genome sequencing for complex organisms has become faster and less expensive. As mounds of genomic data becomes publically available, molecular phylogenetics is continuing to grow and find new applications. 4, 10, 17, 20, 22] The primary objective of molecular phylogenetic studies is to recover the order of evolutionary events and represent them in evolutionary trees that graphically depict relationships among species or genes over time. This is an extremely complex process, further complicated by the fact that there is no one right way to approach all phylogenetic problems. Phylogenetic data sets can consist of hundreds of different species, each of which may have varying mutation rates and patterns that influence evolutionary change.Consequently, there are numerous different evolutionary models and stochastic methods available. The optimal methods for a phylogenetic analysis depend on the nature of the study and data used. [5, 19, 20] Molecular Evolution: Beyond Darwin Evolution is a process by which the traits of a population change from one generation to another. In On the Origin of Species by Means of Natural Selection, Darwin proposed that, given overwhelming evidence from his extensive comparative analysis of living specimens and fossils, all living organisms descended from a common ancestor.The book’s only illustration (see Figure 1) is a tree-like structure that suggests how slow and successive modifications could lead to the extreme variations seen in species today. [11, 27] Molecular Phylogenetics Karen Dowell 2 Figure 1. Evolution Defined Graphically. The sole illustration in Darwin’s Origin of the Species uses a tree-like structure to describe evolution. This drawing shows ancestors at the limbs and branches of the tree, more recent ancestors at its twigs, and contemporary organisms at its buds. [34] Darwin’s theory of evolution is based on three underlying principles: ariation in traits exist among individuals within a population, these variations can be passed from one generation to the next via inheritance, and that some forms of inherited traits provide individuals a higher chance of survival and reproduction than others. [11] Although Darwin developed his theory of evolution without any knowledge of the molecular basis of life, it has since been determined that evolution is actually a molecular process based on genetic information, encoded in DNA, RNA, and proteins. At a molecular level, evolution is driven by the same types of mechanisms Darwin observed at the species level.One molecule undergoes diversification into many variations. One or more of those variants can be selected to be reproduced or amplified throughout a population over many generations. Such variations at the molecular level can be caused by mutations, such as deletions, insertions, inversions, or substitutions at the nucleotide level, which in turn affect protein structure and biological function. [11, 22] What is a Phylogeny? According to modern evolutionary theory, all organisms on earth have descended from a common ancestor, which means that any set of species, extant or extinct, is related.This relationship is called a phylogeny, and is represented by phyloge netic trees, which graphically represent the evolutionary history related to the species of interest (see Figure 2). Phylogenetics infers trees from observations about existing organisms using morphological, physiological, and molecular characteristics. Figure 2. Phylogeny of Mammalia. This phylogenetic tree shows the evolutionary relationships among six orders of Mammalian species (taxa). Taxa listed in grey are extinct. The â€Å"tree of life† represents a phylogeny of all organisms, living and extinct.Other, more specialized species and molecular phylogenies are used to support comparative studies, test biogeographic hypotheses, evaluate mode and timing of speciation, infer amino acid sequence of extinct proteins, track the evolution of diseases, and even provide evidence in criminal cases. [19] Molecular Phylogenetics Karen Dowell 3 Understanding Phylogenetic Trees Before exploring statistical and bioinformatic methods for estimating phylogenetic trees from molecular data , it’s important to have a basic familiarity of the terms and elements common to these types of trees. See Figure 3. ) Figure 3. Basic elements of a phylogenetic tree. Phylogenetic trees are composed of branches, also known as edges, that connect and terminate at nodes. Branches and nodes can be internal or external (terminal). The terminal nodes at the tips of trees represent operational taxonomic units (OTUs). OTUs correspond to the molecular sequences or taxa (species) from which the tree was inferred. Internal nodes represent the last common ancestor (LCA) to all nodes that arise from that point.Trees can be made of a single gene from many taxa (a species tree) or multi-gene families (gene trees). [1, 10] A tree is considered to be â€Å"rooted† if there is a particular node or outgroup (an external point of reference) from which all OTUs in the tree arises. The root is the oldest point in the tree and the common ancestor of all taxa in the analysis. In the absence of a known outgroup, the root can be placed in the middle of the tree or a rootless tree may be generated. Branches of a tree can be grouped together in different ways. (See Figure 4. ) Figure 4.Groups and associations of taxonomical units in trees. A monophyletic group consists of an internal LCA node and all OTUs arising from it. All members within the group are derived from a common ancestor and have inherited a set of unique common traits. A paraphyletic group excludes some of its descendents (for examples all mammals, except the marsupialia Molecular Phylogenetics Karen Dowell 4 taxa). And a polyphyletic group can be a collection of distantly related OTUs that are associated by a similar characteristic or phenotype, but are not directly descended from a common ancestor. 1, 17] Trees and Homology Evolution is shaped by homology, which refers to any similarity due to common ancestry. Similarly, phylogenetic trees are defined by homologous relationships. Paralogs are homologous s equences separated by a gene duplication event. Orthologs are homologous sequences separated by a speciation event (when one species diverges into two). Homologs can be either paralogs or orthologs. [1, 11, 22] Molecular phylogenetic trees are drawn so that branch length corresponds to amount of evolution (the percent difference in molecular sequences) between nodes. 1, 19] Figure 5. Understanding paralogs and orthologs. Paralogs are created by gene duplication events. (See Figure 5. ) Once a gene has been duplicated, all subsequent species in the phylogeny will inherit both copies of the gene, creating orthologs. Interestingly, evolutionary divergence of different species may result in many variations of a protein, all with similar structures and functions, but with very different amino acid sequences. Phylogenetic studies can trace the origin of such proteins to an ancestral protein family or gene. [1, 22] Figure 6. Mirror Phylogenies.Gene A and Gene A1 are paralogs, whereas all i nstances of Gene A are orthologs of each other in different Canid species. One way to ensure that paralogs and orthologs are appropriately referenced in a phylogenetic tree, and guard against misrepresentation due to missing or incomplete taxonomic information is to generate mirror phylogenies (see Figure 6) in which paralogs serve as each other’s outgroup. [1, 4, 19, 22] Estimating Molecular Phylogenetic Trees Molecular phylogenetic trees are generated from character datasets that provides evolutionary content and context.Character data may consist of biomolecular sequence alignments of DNA, RNA, or amino acids, molecular markers, such as single nucleotide polymorphisms (SNPs) or restriction fragment length polymorphisms (RFLPs), morphology data, or information on gene order and content. Evolution is modeled as a process that changes the state of a character, such as the type of nucleotide (AGTC) at a Molecular Phylogenetics Karen Dowell 5 specific location in a DNA sequence ; each character is a function that maps a set of taxa to distinct states. 1, 19] Note that most of the examples in this paper use DNA sequences as character data, but trees can be accurately estimated from many different types of molecular data. Figure 7. Evolution of a DNA Sequence Figure 7 illustrates how a molecular sequence might evolve over time as a result of multiple mutations that results small, but evolutionarily important changes in a nucleotide sequence. At the protein level, these changes may not initially affect protein structure or function, but over time, they may eventually shape a new purpose for a protein within divergent species. 10, 19, 22] OTUs can be used to build an unrooted phylogenetic tree that clearly depicts a path of evolutionary change. Steps in Phylogenetic Analysis Although the nature and scope of phylogenetic studies may vary significantly and require different datasets and computational methods, the basic steps in any phylogenetic analysis remain t he same: assemble and align a dataset, build (estimate) phylogenetic trees from sequences using computational methods and stochastic models, and statistically test and assess the estimated trees. 4, 19, 20] Assemble and Align Datasets The first step is to identify a protein or DNA sequence of interest and assemble a dataset consisting of other related sequences. For example, to explore relationships among different members of the Notch family of proteins, one might select DNA sequences for Notch1 through Notch4, in different species, such as human, dog, rat, and mouse, then perform a multiple sequence alignment to identify homologies. [1, 10, 13, 19, 20] There are a number of free, online tools available to simplify and streamline this process. DNA sequences of interest can be retrieved using NCBI BLAST or similar search tools.When evaluating a set of related sequences retrieved in a BLAST search, pay close attention to the score and E-value. A high score indicates the subject seque nce retrieved with closely related to the sequence used to initiate the query. The smaller the E-value, the higher the probability that the homology reflects a true evolutionary relationship, as opposed to sequence similarity due to chance. As a general rule, sequences with E-values less than 10-5 are homologs of a query sequence. [10] Once sequences are selected and retrieved, multiple sequence alignment is created.This involves arranging a set of sequences in a matrix to identify regions of homology. Typically, gaps (one or more spaces in the alignment) are introduced in one or more sequences to represent insertions or deletions in the molecular code that may have occurred over time. Effective multiple sequence alignment hinged on gap analysis—determining where to insert gaps and how large to make them. There are many websites and software programs, such as ClustalW, MSA, MAFFT, and T-Coffee, designed to perform multiple sequence on a given set of molecular data. ClustalW i s currently the most mature and most widely used. 1, 10. 19] Molecular Phylogenetics Karen Dowell 6 Building Phylogenetic Trees To build phylogenetic trees, statistical methods are applied to determine the tree topology and calculate the branch lengths that best describe the phylogenetic relationships of the aligned sequences in a dataset. Many different methods for building trees exist and no single method performs well for all types of trees and datasets. The most common computational methods applied include distance-matrix methods, and discrete data methods, such as maximum parsimony and maximum likelihood. 4, 17, 20] There are several software packages, such as Paup*, PAML, PHYLIP, that apply most popular methods. [4] Paup* is a commercially available program that implements a wide variety of methods for phylogenetic inference, including maximum likelihood analysis for DNA data using different models. Paup* also includes a set of exact and heuristic methods for searching optimal trees. PAML (Phylogenetic Analysis by Maximum Likelihood) is open-access set of programs for phylogenetic analysis and evolutionary model comparison.PAML includes many advanced models—DNA- and AAbased models as well as codon-based models that can be used to detect positive selection. Many of the programs in PAML can model heterogeneity of evolutionary rates among sequence sites using ? distributions, and evolutionary dynamics of different sequence regions (concatenated gene sequences). PHYLIP is another large suite of open-access programs for phylogenetic inference that estimates trees using numerous methods, including pairwise distance, maximum parsimony, and maximum likelihood.The maximum likelihood programs can handle a few simple stochastic models and have good tree searching capabilities. PHYLIP is generally considered good educational software for novice phylogeneticists. Distance-Matrix Methods Distance matrix methods compute a matrix of pairwise â€Å"distances† between sequences that approximate evolutionary distance. Distance-based methods tend to be in polynomial time and are quite fast in practice. These methods use clustering techniques to compute evolutionary distances, such as the number of nucleotide or amino acid substitutions between sequences, for all pairs of taxa.They then construct phylogenetic trees using algorithms based on functional relationships among distance values. There are several different distance-matrix methods, including the Unweighted Pair-Group Method with Arithmetic Mean (UPGMA), which uses a sequential clustering algorithm; the Transformed Distance Method, which uses an outgroup as a reference, then applies UPGMA; the Neighbor-Relations Method, which applies 4point condition to adjust the distance matrix, then applies UPGMA; and the Neighbor-Joining Method, which arranges OTUs in a star, the finds neighbors sequentially to minimize total length of tree. 4, 17] The following section on the UPGMA method prov ides a more detailed example of how distance-matrix methods work. UPGMA Method UPGMA produces rooted trees for which the edge lengths can be viewed as times measured by a molecular clock with a constant rate. This method uses a sequential clustering algorithm to identify two OTUs that are most similar (meaning they have the shortest evolutionary distance and are most similar in sequence) and treat them as a single new composite OTU. This process is repeated iteratively until only two OTUs remain.The algorithm defines the distance (d) between two clusters Ci and Cj as the average distance between pairs of sequences from each cluster: Molecular Phylogenetics Karen Dowell 7 Where |Ci| and |Cj| are the number of sequences in clusters i and j. This sequential clustering process is visually described in Figure 8. In this example, the two most homologous sequences are 1 and 2. They are clustered into a new composite parent node (6), and the branch lengths (t1 and t2) are defined as 1/2d1,2 . The next step is to search for the closest pair among remaining sequences and node 6.Pair 4 and 5 are identified and clustered into a new parent node (7), and the branch length for t4 and t5 is calculated. [4, 17] Figure 8. Sequential clustering of sequences using the UPGMA method. [17] In this interactive process, parent node 8 is created from pairs 7 and 3, and parent node 9 is created by clustering nodes 6 and 8. [4, 17] Thus, all sequences are clustered into a single evolutionary tree. The total time (t9) can be calculated as: D6,8 = 1/6 (d1,3 + d1,4 + d1,5 + d2,3 + d2,4 +d2,5)Discrete Data Methods Discrete data methods examine each column of a multiple sequence alignment dataset separately and search for the tree that best represents all this information. Although distance-based methods tend to be much faster than discrete data methods, they typically yield little information beyond the basic tree structure. Discrete data analyses, on the other hand, are information rich. The se methods produce a separate tree for each column in the alignment, so it is possible to trace the evolution for specific elements within a given sequence, such as catalytic sites or regulatory regions. 10, 17, 19, 20) Commonly used discrete data methods include maximum parsimony, which searches for the most parsimonious tree that requires the least number of evolutionary changes to explain differences observed, maximum likelihood, which requires a probabilistic model for the process of nucleotide substitution, and Bayesian MCMC, which also requires a stochastic model of evolution, but creates a probability distribution on a set of trees or aspects of evolutionary history. [17, 19, 20] Discrete data methods are generally considered to produce the best estimates of evolutionary history.However, these methods can be computationally expensive, and it can take weeks or months to obtain a reasonable level of accuracy for moderate to large datasets with 100 or more OTUs. [19] Molecular P hylogenetics Maximum Parsimony Karen Dowell 8 Among the most widely used tree-estimation techniques, maximum parsimony applies a set of algorithms to search for the tree that requires the minimum number of evolutionary changes observed among the OTUs in the study. For example, Figure 9 lists four sample sequences from which phylogenetic trees could be inferred using maximum parsimony.Site Seq 1 2 3 4 1 A A A A 2 A G G G 3 G C A A 4 A C T G 5 G G A A 6 T T T T 7 G G C C 8 C C C C 9 A G A G Figure 9. Sample sequences for a maximum parsimony study [17] Maximum parsimony algorithms identify phylogenetically informative sites, meaning the site favors some trees over others. Consider the sequences in Figure 9: Site 1 is not informative, because all sequences at that site (in column 1) are A (Adenine), and no change in state is required to match any one sequence (1-4) to another.Similarly, Site 2 is not informative because all three trees require one change and there is no reason to favor one tree over another. Site 3 is not informative because all three trees require two changes. (See Figure 10). Figure 10. Site 3 trees all require one evolutionary change. [17] Site 4 is not informative because all three trees require three changes. No one tree can be identified as parsimonious. (See Figure 10 Figure 11. Site 4 trees all require three evolutionary changes. [17] Site 5 is informative because one tree requires only one nucleotide change, whereas the other two trees require 2 changes.In Figure 12, the first tree on the left, which requires only one nucleotide change, is identified as the maximum parsimony tree. Figure 12. Site 5 trees vary in the number of evolutionary changes required. [17] Molecular Phylogenetics Maximum Likelihood Karen Dowell 9 The maximum likelihood method requires a probabalistic model of evolution for estimating nucleotide substitution. This method evaluates competing hypotheses (trees and parameters) by selecting those with the highest likeliho od, meaning those that render the observed data most plausible. The ikelihood of a hypothesis is defined as the probability of the data given that hypothesis. In phylogeny reconstruction, the hypotheses are the evolutionary tree (its topology and branch lengths) and any other parameters of the evolutionary model. [17, 20] The likelihood calculations required for evolutionary trees are far from straightforward and usually require complex computations that must allow for all possible unobserved sequences at the LCA nodes of hypothesized trees. This method specifies the transition probability from one nucleotide state to another in a time interval in each branch.For example, for a one-parameter model with rate of substitution ? per site per unit time, the probability that the nucleotide at time t is i is: The probability that the nucleotide at time t is j is: To set up a likelihood function, given x as the ancestral node and y and z as internal nodes, the probability of observing nucle otides i, j, k, l at the tips of the tree is computed as: Pxl(t1+t2+t3)Pxy(t1)Pyk(t2+t3)Pyz(t2)Pzi(t3)Pzj(t3) For the ancestral node (root) x, the probability of having nucleotide l in sequence 4 is calculated as: Pxl(t1+t2+t3)Because x, y, and z can be any one of four nucleotides (ACGT), it is necessary to sum over all possibilities to obtain the probability of observing the configuration of nucleotides i, j, k, l, in sequences 1, 2, 3, 4, for a given hypothetical tree (see Figure 13. ). This likelihood probability is calculated as: h(I,j,k,l)= [? gxPxl(t1+t2+t3)] [? Pxy(t1)Pyk(t2+t3)] [? Pyz(t2)Pzi(t3) Pzj(t3)] The appropriate likelihood function depends on the hypothetical tree and the evolutionary model used. (See Figure 13. ) [17] Figure 13. Different types of model trees for the derivation of the maximum likelihood function. 17] Molecular Phylogenetics Stochastic Models of Evolution Karen Dowell 10 Evolutionary changes in molecular sequences result from mutations, some of whic h occur by chance, others by natural selection. Rates of change can also differ among OTUs, depending on several factors ranging from GC content to genome size. To accurately estimate phylogenetic trees, assumptions must be made about the substitution process and those assumptions must be stated in the form of a stochastic evolutionary model. These probabilistic models are used to rank trees according to likelihood: P(data|tree).From a Bayesian perspective, they rank trees according to a posterior probability: P(tree|data). [17, 20] The objective of probabilistic models is to find likelihood or posterior probability of a particular taxonomic feature, then define and compute: P(x? |T,t ? ) Where x ? is xj for j=1†¦n, T is a tree with n leaves with sequence j at leaf j, and t ? are tree edge lengths. [17] A few popular stochastic models of evolution include the single parameter Jukes-Cantor (JC) method, Kimura 2-parameter (K2P), Hasegawa-Kishino-Yano (HKY), and Equal-Input.Some s oftware programs, such as Paup*, will automatically use a default model for the tree estimation method chosen. The JC method is the easiest one to comprehend, because it assumes that if a site changes its state, it changes with equal probability to the other states. This is not very realistic, however, as some sites are known to evolve more rapidly than others, and some sites may be invariable and not allowed to change at all. Determining how best to select the appropriate model is a topic of another paper (or papers) as there is no one model that incorporates all mutation rules and patterns across different species and macromolecules. 4, 17, 20] Hidden Markov Models Profile hidden Markov models (HMMs) are a form of Bayesian network that provides statistical models of the consensus structure of a sequence family. Gary Churchill at The Jackson Lab was the first evolutionary geneticist to propose using profile HMMs to model rates of evolution. Many software packages and web services n ow apply HMMs to estimate phylogenetic relationships. [8] In the HMM format, each position in the model corresponds to a site in the sequence alignment. For each position, there are a number of possible states, each of which corresponds to a different rate of evolution.In addition, transitions between all possible rate-states at adjacent positions. Transition probabilities capture any tendency for patterns of rates to occur in successive sites. [2, 4] Assessing Trees Tree estimating algorithms generate one or more optimal trees. This set of possible trees is subjected to a series of statistical tests to evaluate whether one tree is better than another – and if the proposed phylogeny is reasonable. Common methods for assessing trees include the Bootstrap and Jackknife Resampling methods, and analytical methods, such as parsimony, distance, and likelihood.To illustrate how these methods are used, consider the steps involved in a bootstrap analysis. Bootstrap Analysis A bootstra p is a statistical method for assessing trees that takes its name from the fact that it can â€Å"pull itself up by its bootstraps† and generate meaningful statistical distributions from almost nothing. Using bootstrap analysis, distributions that would otherwise be difficult to calculate exactly are estimated by repeated creation and analysis of artificial datasets. In a Non-parametric bootstrap, artificial datasets Molecular Phylogenetics Karen Dowell 11 generated by resampling from original data.In a parametric bootstrap, data is simulated according to hypothesis tested. The objective of any bootstrap analysis is to test whether the whole dataset supports the tree. [1, 4, 17] Figure 14 illustrates the basic steps in any bootstrap analysis. Sample datasets are automatically generated from an original dataset. Trees are then estimated from each sample dataset. The results are compiled and compared to determine a bootstrap consensus tree. Figure 14. Steps in a phylogenetic tr ee bootstrap analysis. [1] Phylogenetic Analysis Tools There are several good online tools and databases that can be used for phylogenetic analysis.These include PANTHER, P-Pod, PFam, TreeFam, and the PhyloFacts structural phylogenomic encyclopedia. Each of these databases uses different algorithms and draws on different sources for sequence information, and therefore the trees estimated by PANTHER, for example, may differ significantly from those generated by P-Pod or PFam. As with all bioinformatics tools of this type, it is important to test different methods, compare the results, then determine which database works best (according to consensus results, not researcher bias) for studies involving different types of datasets.In addition, to the phylogenetic programs already mentioned in this paper, a comprehensive list of more than 350 software packages, web-services, and other resources can be found here: http://evolution. genetics. washington. edu/phylip/software. html. PANTHER ( pantherdb. org) Protein ANalysis Through Evolutionary Relationships, known by its acronym PANTHER, is a library of protein families and subfamilies indexed by function. Panther version 6. 1 contains 5547 protein families. Molecular Phylogenetics Karen Dowell 12It categorizes proteins by evolutionary related proteins (families) and related proteins with same function (subfamilies). [8, 21, 26] PANTHER is composed of both a library and index. The library is a collection of â€Å"books† that represent a protein family as a collection of multiple sequence alignments, HMMs, and a family phylogenetic tree. Functional divergence within the tree is represented by dividing the parent tree into child trees and HMMs based on shared functions. These subfamilies enable database curators to more accurately capture functional divergence of protein sequences as inferred from genomic DNA. 25, 26] PANTHER database entries are annotated to molecular function, biological process and pathway with a proprietary PANTHER/X ontology system, which is supposed to be easier to understand than the more global standard Gene Ontology (GO). Database entries in PANTHER are generated through clustering of UniProt database using a BLAST-based similarity score. Trees are automatically generated based on multiple sequence alignments and parameters of the protein family HMMs using the Tree Inferred from Profile Score (TIPS) clustering algorithm.Scientific curators review all family trees, annotate each tree, and determine how best to divide them into subtrees using a tree-attribute viewer that tabulates annotations for sequences in a tree. In addition, trees and subfamilies are manually cross-checked and validated by curators. [25, 26] P-POD (ortholog. princeton. edu) The Princeton Protein Orthology Database (P-POD) combines results from multiple comparative methods with curated information culled from the literature.Designed to be a resource for experimental biologists seeking evolutionary information on genes on interest, P-POD employs a modular architecture, based on their Generic Model Organism Database (GMOD). P-POD can be accessed from their web service or downloaded to run on local computer systems. [12] P-POD accepts FASTA-formatted protein sequences as input, and performs comparative genomic analyses on those sequences using OrthoMCL and Jaccard clustering methods. The P-POD database contains both phylogenetic information and manually curated experimental results.The site also provides many links to sites rich in human disease and gene information. This tool may be particularly helpful for bioinformaticists and statisticians developing comparative genomic database tools and resources. Pfam (pfam. sanger. ac. uk/) PFam is a collection of protein families represented by multiple sequence alignments and HMMs. It contains models of protein clans, families, domains, and motifs, and uses HMMs representing conserved functional and structural domains. It is a large, widely used, actively curated mature database that has been available online since 1995.Pfam can be used to retrieve the domain architectures for a specific protein by conducting a search using a protein sequence against the Pfam library of HMMs. This database is also helpful for proteomes and protein domain architecture analysis. [6, 8, 24] There are two versions of the Pfam database: Pfam–B is generated automatically from ProDom, using PsiBLAST, an open access bioinformatics tool available through NCBI for identifying weak, but biologically relevant sequence similarities. Pfam-A is hand-curated from custom multiple sequence alignments. Pfam protein domain families are clustered with Mkdom2, and aligned with ProDomAlign.ProDom is a comprehensive set of protein domain families automatically generated from the SWISSPROT and TrEMBL sequence databases. Mkdom2 is a ProDom program used to make ProDom family clusters. Protein domain families in ProDom were aligned using an improved parallelized program called Molecular Phylogenetics Karen Dowell 13 ProDomAlign, developed in C++ using OpenMP. ProDomAlign is based on MultAlign, a program well suited for aligning very large sequence families with thousands of associated sequences. As of early 2008, Pfam matched 72 percent of known proteins sequences, and 95 percent of proteins for which there is a known structure.Within the Pfam database, 75 percent of sequences will have one match to Pfam-A, 19 percent to Pfam-B. There are also two versions of Pfam-A and Pfam-B. Pfam-ls handles global alignments, and Pfam-fs is optimized for local alignments. Interestingly, Pfam entries can be classified as â€Å"unknown,† but that doesn’t mean the protein is undocumented. Unknown entries can be proteins for which some information is known, but it has not been fully researched or cannot be adequately annotated. For example, Pfam entry PFO1816 is a LeucineRich Repeat Variant (LRV), which has a known structure (1LRV ) available in the Protein Databank (pdb. rg). LRV repeat regions, which are found in many different proteins, are often involved in cell adhesion, DNA repair, and hormone reception—but identification of an LRV within a sequence encoding a protein doesn’t specifically reveal the protein’s function. For studies involving a large number of protein searches, it may be more convenient to run Pfam locally on a client machine. The standalone Pfam system requires the HMMER2 software, the Pfam HMM libraries and a couple of additional files from the Pfam website to be installed on the client machine. HMMER is a freely distributable implementation of profile HMM software for protein sequence analysis. ) Once the initial search is complete, researchers can go to the Pfam website to further analyze select number of sequences using additional features on website. [6, 8, 24] TreeFam (TreeFam. org) TreeFam is a curated database of phylogenetic trees and orthology predictions f or all animal gene families that focuses on gene sets from animals with completely sequenced genomes. Orthologs and paralogs are inferred from phylogenetic tree of gene family.Release 4 contains curated trees for 1314 families and automatically generated trees for another 14351 families. [16, 23] Like Pfam, TreeFam is a two-part database: TreeFam-B contains automatically generated trees, and TreeFam-A consists of manually curated trees. To automatically generate trees, an algorithm selects clusters of genes to create TreeFam-B â€Å"seeds† from core species with high-quality reference genome sequences, first using BLAST to rapidly assemble an initial list of possible matches, then HMMER to expand and filter probable sequence matches for each TreeFam B seed family.The filtered alignment is fed into a neighbor-joining algorithm and a tree is constructed based on amino acid mismatch distances. For TreeFam version 4, the most current release, five â€Å"clean† family trees were built for each TreeFam B seed, two using a maximum likelihood tree generated using PHYML (one based on the protein alignment, the other on codon alignment), three using a neighbor joining tree, using different distance measurements based on codon alignments. 16, 23] Scientific curators then manually any correct errors (based on information in the literature) in automatically generated TreeFam-B trees. Curated TreeFam-B trees then become seeds for TreeFam-A trees. Clean TreeFam-A trees are build using three merging algorithms and bootstrapping to find the consensus tree of seven trees: two constrained maximum likelihood trees based on protein and codon alignment, and five unconstrained neighbor-joining trees generated using different distance measurements based on codon alignments.For both TreeFam-B and TreeFam-A families, orthologs and paralogs are inferred only from clean trees using Duplication/Loss Inference (DLI) algorithm that requires a species tree (NCBI taxonomy tree). [16, 23] Molecular Phylogenetics PhyloFacts (phylogenomics. berkeley. edu/phylofacts) Karen Dowell 14 PhyloFacts is an online phylogenomic encyclopedia for protein functional and structural classification. It contains more than 57,000 â€Å"books† for protein superfamilies and structural domains.Each book contains heterogenous data for protein families, including multiple sequence alignments, one or more phylogenetic trees, predicted 3-D protein structures, predicted functional subfamilies, taxonomic distributions, GO annotations, and PFAM domains. HMMs constructed for each family and subfamily permit novel sequences to be classified to different functional classes. [14] Unlike other databases mentioned in this paper, PhyloFacts seeks to correct and clarify annotation errors associated with computational methods for predicting protein function based on sequence homology.It uses a consensus approach that integrates many different prediction methods and sources of experimental data over an evolutionary tree. By applying evolutionary and structural clustering of proteins, PhyloFacts is able to analyze disparate datasets using multiple methods, identify potential errors in database annotations, and provide a mechanism for improving the accuracy of functional annotation in general. [14] PhyloFacts can be used to search for protein structure prediction or functional classification for a particular protein sequence.Researchers may also browse through protein family books and multiple sequence alignments, phylogenetic trees, HMMs and other pertinent information for proteins of interest. This webservice also provides many links to literature and other information sources. [14] Applied Molecular Phylogenetics Molecular phylogenetic studies have many diverse applications. As the amount of publically available molecular sequence data grows and methods for modeling evolution become more sophisticated and accessible, more and more biologists are incorporating phylog enetic analyses into their research trategy. Here’s a sampling of how molecular phylogenetics might be applied. Tracing the evolution of man In one case study, molecular phylogenetic techniques were used to compare and analyze variation in DNA sequences using modern human and Neanderthal mitochondrial DNA (mtDNA). For this study, 206 modern human mtDNAs and parts of two Neanderthal mtDNAs sequences derived from skeletal remains were used to generate an initial dataset. Genetic distance was first estimated using the Jukes-Cantor single parameter model.Then the Kimura 2-Parameter model was used to distinguish between transition (replacement of one purine with another purine or one pyrimidine with another pyrimidine) and transversion (replacement of one purine with a pyrimidine or vice versa) probabilities with Kimura 2parameter model. A phylogenetic tree representing primate evolution was generated using pairwise genetic distances between primate Hypervariable regions I and II of mtDNA. [3] Chasing an epidemic: SARS Using publically available genomic data, it is possible to reconstruct the progression of the SARS epidemic over time and geographically.To conduct this phylogenetic analysis, researchers used the neighborjoining method to construct a phylogenetic tree of spike proteins in various coronaviruses and identify the viral host (a Himalyan palm civet). They then obtained 13 SARs genome sequences with documented information on the date and location of the sample. The neighbor-joining method and a distance matrix based on Jukes-Cantor model, were used to generate an epidemic tree, from which it was possible to identify the origin (date and location) of the virus by observing progression of mutations over time. 3] Molecular Phylogenetics Barking up the right tree Karen Dowell 15 Phylogenetics is increasingly incorporated into biological and biomedical research papers. When the canine genome was published, researchers used sequence data to estimate a co mprehensive phylogeny of the canid family. Figure 15. Phylogenetic Tree of the Canid family This canid family phylogenetic tree is based on 15 kb of exon and intron sequence. It was constructed using the maximum parsimony method and represents the single most parsimonious tree.A good example of how phylogenies are referenced in the literature, this tree includes bootstrap values and Bayesian posterior probability values listed above and below internodes, respectively. Dashes indicate bootstrap values below 50%. In addition, divergence time in millions of years (Myr) is indicated for three nodes. [18] Seeing the Forest from the Trees Molecular phylogenetics is a broad, diverse field with many applications, supported by multiple computational and statistical methods. The sheer volumes of genomic data currently available (and rapidly growing) render molecular phylogenetics a key component of much biological research.Genome-scale studies on gene content, conserved gene order, gene expre ssion, regulatory networks, metabolic pathways, functional genome annotation can all be enriched by evolutionary studies based on phylogenetic statistical analyses. [19, 25 27] Molecular phylogenies have fast become an integral part of biological research, pharmaceutical drug design, and bioinformatics techniques for protein structure prediction and multiple sequence alignment. Although not all molecular biologists and bioinformaticians may be familiar with the techniques describedMolecular Phylogenetics Karen Dowell 16 in this paper, this is a rapidly growing and expanding field and there is ongoing need for novel algorithms to solve complex phylogeny reconstruction problems. References 1. Baldauf, SL (2003) â€Å"Phylogeny for the faint of heart: a tutorial. † Trends in Genetics, 19(6):345-351. 2. Brown, D, K Sjolander (2006) â€Å"Functional Classification Using Phylogenomic Inference. † PLos Computational Biology, 2(6):0479-0483. 3. Cristianini, N, and M Hahn (2007 ) Introduction to Computational Genomics: A Case Studies Approach.Cambridge University Press: Cambridge. 4. Durbin, R, S Eddy, A Krogh, G Mitchison (1998) Biological Sequence Analysis. Cambridge University Press: Cambridge. 5. Ewens, WJ, R Grant (2005) Statistical Methods in Bioinformatics. Springer Science and Business Media: New York. 6. Finn, RD, J Tate, J Mistry, PC Coggill, SJ Sammut, HR Hotz, G Ceric, K Forslund, SR Eddy, ELL Sonnhammer, A Bateman (2008) â€Å"The Pfam protein families database. † Nucleic Acids Research, 36:D281288. 7. Gabaldon, T (2008) â€Å"Large-scale assignment of orthology: back to phylogenetics? Genome Biology, 9:235. 1-235. 6. 8. Gollery, M. (2008) Handbook of Hidden Markov Models in Bioinformatics. CRC Press, Taylor & Francis Group: London. 9. Goodstadt, L, CP Ponting (2006) â€Å"Phylogenetic Reconstruction of Orthology, Paralogy, and Conserved Synteny for Dog and Human. † PLoS Computational Biology, 2(9):1134-1150. 10. Hall, BG. (2004 ) Phylogenetic Trees Made Easy: A How-To Manual, 2nd ed. Sinauer Associates, Inc. : Sunderland, MA. 11. Hartwell, LH, L Hood, ML Goldberg, AE Reynolds, LM Silver, RC Veres (2008) Genetics: From Genes to Genomes, 3rd Ed.McGraw-Hill: New York. 12. Heinicke, S, MS Livstone, C Lu, R Oughtred, F Kang, SV Angiuoli, O White, D Botstein, K Dolinski (2007) â€Å"The Princeton Protein Orthology Database (P-POD): A Comparative Genomics Analysis Tool for Biologists. † PLoS ONE, 8:e766. 1-15. 13. Kortschak, RD, R Tamme (2001) â€Å"Evolutionary analysis of vertebrate Notch genes. † Dev Genes Evol, 211:350-354. 14. Krishnamurthy, N, DP Brown, D Kirshner, K Sjolander (2006) â€Å"PhyloFacts: an online structural phylogenomic encyclopedia for protein functional and structural classification. † Genome Biology, 7:R83. -13. 15. Kuzniar, A, RCHJ van Ham, S Pongor, JAM Leunissen (2008) â€Å"The quest for orthologs: finding the corresponding gene across genomes. † Trends in G enetics, 24(11):539-551. Molecular Phylogenetics Karen Dowell 17 16. Li, H, A Coghlan, J Ruan, LJ Coin, JK Heriche, L Osmotherly, R Li, T Liu, Z Zhang, L Bolund, GKS Wong, W Zheng, P Dehal, J Wang, R Durbin (2006) â€Å"TreeFam: a curated database of phylgenetic trees of animal gene families. † Nucleic Acids Research, 34:D573-580. 17. Li, WH (1997) Molecular Evolution. Sinauer Associates: Sunderland, MA. 18.Lindblad-Toh, K, CM Wade, TS Mikkelsen, EK Karlsson, DB Jaffe, M Kamal, M Clamp, JL Chang, EJ Kulbokas III, MC Zody, E Mauceli, X Xie, M Breen, RK Wayne, EA Ostrander, CP Ponting, F Galibert, DR Smith, PJ deJong, E Kirkness, P Alvarez, T Biagi, W Brockman, J Butler, C Chin, A Cook, J Cuff, MJ Daly, D DeCaprio, S Gnerre, M Grabherr, M Kellis, M Kleber, C Bardeleben, L Goodstadt, A Heger, C Hitte, L Kim, KP Koepfli, HG Parker, JP Pollinger, SMJ Searle, NB Sutter, R Thomas, C Webber, ES Lander (2005) â€Å"Genome Sequence, Comparative Analysis and Haplotype Structure of the Domestic Dog.Nature, 438:803-819. 19. Linder, CR, T Warnow (2005) â€Å"An overview of phylogeny reconstruction. † In the Handbook of Computational Molecular Biology, Chapman and Hall/CRC Computer & Information Science. 20. Lio, P, N Goldman (1998) â€Å"Models of Molecular Evolution and Phylogeny. † Genome Research, 8:12331244. 21. Mi, H, N Guo, A Kejariwal, PD Thomas (2007) â€Å"PANTHER version 6: protein sequence and function evolution data with expanded representation of biological pathways. Nucleic Acids Research, 35:D247-252. 22. Patthy, Laszlo. (1999) Protein Evolution. Blackwell Science, Ltd: Malden, MA. 23. Ruan, J, H Li Z Chen, A Coghlan, LJM Coin, Y Guo, JK Heriche, Y Hu, K Kristiansen, R Li, T Liu, A Mose, J Qin, S Vang, AJ Vilella, A Ureta-Vidal, L Bolund, J Wang, R Durbin (2008) â€Å"TreeFam: 2008 Update. † Nucleic Acids Research, 36:D735-740. 24. Sammut, SJ, RD Finn, A Bateman (2008) â€Å"Pfam 10 years on: 10000 families and still growing. â €  Briefings in Bioinformatics, 9(3):210-219. 5. Thomas, PD, A Kejariwal, N Guo, H Mi, MJ Campbell, A Muruganujan, B Lazareva-Ulitsky (2006) â€Å"Applications for protein sequence-function evolution data: mRNA/protein expression analysis and coding SNP scoring tools. † Nucleic Acids Research, 34:W645-650. 26. Thomas, PD, MJ Campbell, A Kejariwal, H Mi, B Karlak, R Daverman, K Diemer, A Muruganujan, A Narechania. â€Å"PANTHER: A Library of Protein Families and Subfamilies Indexed by Function. † Genome Research, 13:2129-2141. 27.Warnow, T (2004) â€Å"Computational Methods in Phylogenetics† Computational Systems Biology Conference, Stanford, CA 28. Whelan, S, P Lio, N Goldman (2001) â€Å"Molecular phylogenetics: state of the art methods for looking into the past. † Trends in Genetics, 17(5):262-272. Molecular Phylogenetics Karen Dowell 18 Appendix Website Resources Phylogeny Programs. A University of Washington site formerly supported by the National Science Foundation. http://www. evolution. genetics. washington. edu/phylip/software. tml TreeFam Tree Families Database. http://wwww. treefam. org Protein Analysis Through Evolutionary Relationships (PANTHER) Classification System. http://www. pantherdb. org. 29. Pfam Database of Protein Families. http://pfam. sanger. ac. uk 30. Princeton Protein Orthology Database (P-POD). http://ppod. princeton. edu 31. Wikipedia. http://en. wikipedia. org/wiki/Tree_of_life(science) Cover Page The cover image is from a phylogeny of canid species that appeared in Lindblad-Toh et al, 2005. [18]

Humour in ‘Pride and Prejudice’

Humour is a key theme in the novel â€Å"Pride and Prejudice.† It plays a major role in entertaining the reader and providing important characteristics and features of the characters in the novel. Humour is shown in the responses of characters towards one another and the episdary style, which creates humour as it is written from the point of view of the character rather than the style in which the rest of the novel is written in. In chapters 1-20 the reader learns about the character of Mr.Collins. Mr.Bennet's estate brings him two thousand pounds a year, but on his death a distant male relative, Mr.Collins, will inherit both his estate and this income. In chapter 13, Mr.Bennet receives a letter from Mr.Collins in which Mr.Collins informs Mr.Bennet that he will be joining them for dinner. In his letter, Mr.Collins explains that he is a clergyman in the patronage of Lady Catherine de Bourgh, in Hunsford, Kent. He hints a way of resolving the problem of entailment and proposes to visit the family for a week. Jane Austin's use of the letter in chapter 13 is a very clever introduction to the character of Mr.Collins as it gives the reader a brief insight to his character even before the reader meets him. The letter reveals Mr.Collins as a person with an astonishing pomposity. We also learn that he is artificial, haughty, proud and very self-important. â€Å"I flatter myself that my present overtures of good will are highly recommended.† The pedantically worded letter reveals Mr.Collins's artificiality. Furthermore, humour is conveyed in Mr.Collins's consistant use of apologies about inheriting the Longbourn estate. â€Å"I cannot be otherwise than concerned at being the means of injuring your amiable daughters, and beg leave to aplogise for it, as well as to assure you of my readiness to make them every possible amends- but of this hereafter.† Chapter 13. This may have seemed very comical to the reader as Mr.Collins feels that his apology will make the Bennets like him. This reinforces how shallow, insincere and single-minded Mr.Collins actually is. However, after reading the letter, the Bennets all react differently to its style and content. These comments and reactions are used to contrast their characters and perceptions. Mrs.Bennet is immediately placated by Mr.Collins's heavy hints, which suggest that he is thinking of marrying one of her girls. This reinforces Mrs.Bennet's shallowness. Jane approves of his good intentions, which reinforces the point that she is naive. However, Elizabeth questions his sense, which shows her â€Å"quickness†. Mary commends his clicheed composition, whereas, Catherine and Lydia are not interested as he is not a soldier. Mr.Bennet meanwhile looks forward to the enjoyment of Mr.Collins's folly. As does the reader. Later on, after his arrival at the Bennets' estate, Mr.Collins is given a tour of the house not merely in general but to view for value, as he will acquire the property in the future. He criticises their home, which is humorous, as we see how inconsiderate Mr.Collins is. He also does not seem to realise how he may be offending the Bennets. Mr.Collins thinks highly of himself. His language is pedantically worded which shows us that he is trying to convey that he is an intellectual person. The character of Mr.Collins can be likened to the character of Mary, as, although they are both intelligent, they are very artificial in the way in which they present their intelligence to an audience. Mr.Collins uses long sentences in the letter, which portray the shallowness of his character. In chapter 20, when Mr.Collins proposes to Elizabeth, his speech is stilted, pompous and governed by the overweening egotism. His prolix style leads him to break down his speech into numbered points: â€Å"Firstly†¦ secondly†¦ thirdly†¦Ã¢â‚¬  These are unsuitable in a proposal of marriage during which love is proclaimed. Elizabeth nearly laughs at the idea that his business plan is to be presented before he allows his feelings to run away on the subject of the companion that he has chosen for his future life. He shows that he has not considered her views or feelings and he is certain that his offer is an act of generosity. The scene is richly comic, but harsh realities underlie the situation. Collins reminds Elizabeth that since she has so little money to her name, she may never receive another offer of marriage, which shows the reader Mr.Collins's selfishness, rudeness and how inconsiderate he is. Humour is also highlighted in Mr.Collins's marriage proposal when Elizabeth refuses to marry him. He is turned down and this comes as a shock to him. When Elizabeth refuses him, he is determined to see her behaviour as a form of modesty or flirtatiousness, â€Å"the usual practice of elegant females.† The reader comes across absurdity in the way Mr.Collins describes Lady Catherine de Bourgh. He continuously praises her in his letter and compares her with everything and everyone. He says that she is an â€Å"honourable† lady â€Å"whose bounty and beneficence has preferred me to the valuable rectory of his parish, where it shall be my earnest endeavour to demean myself with grateful respect towards her ladyship.† His descriptions of Lady Catherine de Bourgh in the letter are very humorous and Mr.Collins's artificiality is reinforced. This is because he is trying to associate himself with people from the upper class, (although we know he is not as he comes from the same working background as Mr.Bennet). Furthermore, in chapter 16, Mr.Collins, intending a compliment, compares the drawing room to the small breakfast parlour at Rosings, Lady Catherine de Bourgh's estate. Mrs.Philips soon realises that he is tedious snob. Finally, humour throughout â€Å"Pride and Prejudice† has been successful. Throughout chapters 1-20 we see the various ways in which humour is portrayed through the character of Mr.Collins. By using Mr.Collins as the centre of comedy in the novel, Jane Austen entertains the reader and brings a smile to their faces.

A central assumption made in Mean-Variance Analysis and the Capital Coursework

A central assumption made in Mean-Variance Analysis and the Capital Asset Pricing Model (CAPM) is that investors prefer to invest in the most efficient portfolios available - Coursework Example The concept of the efficient portfolio can be well understood after revisiting the preceding portfolio management theories. One such theory is the famous capital assets pricing theory (CAPM). The CAPM is a model that shows the association between the required rate of return and the risk on assets that are held in a portfolio that is well diversified. According to Fama and French (2004), the origin of the capital asset pricing model is the prominent work of William Sharpe (1964) and John Lintner (1965). The CAPM model is very useful in activities such as the determination of the companies’ cost of capital and in assessing portfolio performance. A portfolio is a group of assets (more than one asset) held by an investor (Sharpe 1964). The theory of portfolio attempts to guide investors on how to make the best combination of assets to optimise returns as well as minimise the risk associated with the investments. The commonly used CAPM equation is a follows: ER = Rf + (Rm – Rf)ÃŽ ², where Rf is the risk free rate, ER is the expected return on the portfolio, (usually denoted by the interest rate on treasury bills), Rm is the expected market return for the same period, and ÃŽ ² is the beta, which measures the relationship between the portfolio performance and the market performance. In other words, beta indicates how sensitive the portfolio’s performance is to the variations in the market performance. The above equation shows that a portfolio’s return can be expressed in terms of the risk-free return, the risk premium and the beta. Based on the equation, which is a linear, it is revealed that the portfolio return is directly related to the risk. That is, the higher the portfolio risk, the higher the portfolio’s return. The CAPM theory brings us to another idea of the efficient portfolio. A portfolio can be efficient under