Alphabet Games Essay

A) The analytical framework I have chosen to use is PEST. Pest stands for Political, Economic, Social and Technological and are all factors of a PEST analysis. These are intellectual tools which are created in order to help a researcher to collect, sort, prioritise and interpret a variety of existing data and information about the subject or context that has to be analysed. When changes happen within a business or organisation the company will use a PEST analysis to view each factor in the changing process, in this case we will be looking at the changes of Alphabet Games. Political Factor Political forces include regulatory requirements, legal concerns, and any impact from the current political climate of the country or region where the business operates. The changes in the political factor could effect Alphabet Games considerably as they would have to sell games or consoles at a higher cost if the taxations in the gaming industry increased in order for the company to earn a stable profit. Economic Factors – Any change in the economy that impacts the supply or demand for a company’s products and services fits into this category. Sometimes they have a positive impact, like when a country’s gross domestic product (GDP) increases more than expected. Other times economic forces can hurt a business, like when consumer confidence drops and potential customers spend less and save more.Alphabet Games may need to pay more or less for the resources they need depending on where they purchase these from. As more companies are forming within the industry and all purchasing from the same supplier then the costs may decrease as they will be taking in more money, and this could decrease the price of games and consoles. Social Factors – Social factors are those that reflect the preferences, fads, and trends in society. Media companies are very sensitive to social trends as their business model is to produce content that reflects society’s interests. A social factor which relates to the case study is the force of change within Alphabet Games. Alphabet Games will have to constantly keep up to date with with upcoming and new trends so that they can work towards these. By  checking quantifiable statistics Alphabet Games will be able to see if the community offers a population with the demographic traits necessary to support the business. Technological Factors – Advancement in technology has had a dramatic impact on the business world over the last two centuries, and especially over the last 30 years. Anticipating changes in technology and capitalizing on those changes can become a competitive advantage and so Alphabet Games could be affected by this. Alphabet games will have to be able to change their patterns by creating new games, software and consoles in order to increase sales and marketing. BSWOT Analysis Strengths Close working relationships that exist between the partners Multi-million pound business at the cutting edge of the games development market Custom built facility that houses research, development and production Wide range of corporate and individual customers Extensive experience World known reputation for excellence, quality and innovation They offer software solutions as well as games Passion for software within the company is still as strong as when it established Weaknesses Competition between the small businesses and larger companies Technological enviroment Opportunities Recent growth in demand for flash games Some of their recent clients include NHS, Pepsi, Virgin Media and other small businesses The software can draw potential customers to companies websites providing a competitive marketplace Due to their experience they are a lot faster than most rivalry’s at developing new software Threats The challenge for small companies like Alphabet Games to stay in the market for long term and reap in potential benefits Production costs have tripled in recent years with the introduction of next generation consoles Sales and revenues have increased at a fraction Technology costs have risen which means large investment in staff and equipment CSWOT analysis guidelines In order to carry out an effective SWOT Analysis all information used must be current and relevant to the firm. A SWOT Analysis is a general technique which can be applied across diverse functions and activities used by managers. Using a SWOT Analysis can provide benefits such as a framework for  identifying and analysing strengths, weaknesses, opportunity’s and threats in relation to particular tasks or objectives or a stimulus participation in a group experience as well as many others. Below are a set of guidelines to follow that will enable them to carry out an effective SWOT Analysis. GATHER A TEAM The first step to take when conducting a SWOT analysis is to gather a team who have experience when conducting a SWOT analysis. By gathering a team that have experience they will be able to define the objectives which are relevant and accurate to the firm. PARTICIPATING IN THE SWOT ANALYSIS For best results invite contributors to participate in the swot analysis but by giving them enough time to prepare and conduct their own SWOT in advance. By providing a draft SWOT with brief descriptions of what they think is being seen as strengths, weaknesses, opportunity’s and threats. Once the group has assembled the process and established ground rules should be explained. The process of documenting strengths, weaknesses, opportunity’s and threats should be explained prioritising these lists and using the information as part of the strategic, business marketing plans. Explain that the SWOT process is a cooperative exercise aimed at organisational improvement and not about allocating blame and assure all participations that their input will be respected. Ground rules include – Everyone’s ideas are important Every idea is a good one No-ones idea is better than the other Suggesting an idea does not mean that you will be expected to carry it out if it is respected Except in the case of an emergency, participants commit to remaining on task until completion LIST STENGTHS The group assembled should list their lists of strengths identified before continuing to the workshop. They should be invited to the form in pairs and develop one combined list. The pairs then combine to form fours, and the process is repeated. Set of four then combine to form eight, and then again the process is repeated, each sets of eight then presents its list. The list of strengths is developed incorporating all contributions. The list should then be finalised by asking participants to reword any descriptions or include any additional strengths that may have been considered during the process. LIST WEAKNESSES In order to identify weaknesses a repeat process for strengths should be generated reflecting on the participants contributions. The list will provide a useful indication of growth over a period. When you review the list in a year’s time you may notice that most of the identified weaknesses have disappeared. Even though other weaknesses will be identified, the disappearance of previous ones is an indicator of successful progress. LIST OPPORTUNITIES In order to list the opportunities and threats the process for which was used for strengths and weaknesses should be repeated. The focus now becomes external, as opposed to internal for strengths and weaknesses. Make sure that opportunities and threats are not absolute – one person’s threat can be another’s opportunity, however the same item won’t appear on both lists. ESTABLISH PRIORITIES When the process has been completed there will be four lists developed from everyone’s input. Ideally these lists should be displayed so that participants have an accurate and succinct picture of everyone’s views of  the current situation. The list should then be narrowed down showing top priorities. Clarity of objectives is key to this process as evaluation and elimination will be necessary to cull the wheat from the chaff. With the lists compiled a clear picture should at this stage start to emerge in response to the objectives. CARRY YOUR FINDINGS Make sure that the SWOT analysis is used in subsequent planning. Revisit your findings at suitable time internals to check they are still valid and use lists to identify issues that are crucial to achieving the stated purpose of the business in which the company is involved. It is likely that you will be able to identify specific themes across all four lists. Try to restrict the number of themes if possible.

How effective an adaptation of the play Macbeth is the film ‘Macbeth on the Estate’?

Macbeth on the Estate is a modern adaptation of Macbeth. It is set on a modern, run-down housing estate in Birmingham. The major changes from the play are the setting and the characters. There are much fewer noble qualities about the people and places shown. Instead, the setting is very run-down and poor. The characters are also corrupt and indulgent. A lot of the blame for the bad things that happen in the play seems to be given to characters. For example, the possibility that the witches control Macbeth, and he is not in control is implied to be untrue by suggesting that the effects that seem to be supernatural are simply caused by drugs and the poor conditions. There are also some things done that cannot be done in a theatre, such as camerawork to direct the audience. I believe that the film is a reasonable good conversion of the play into a modern film. I believe that it managed to portray the meaning of the original in a modern way that is easy to understand for modern people, as well as making suggestions about the story. I like how every aspect of Shakespearean world was converted into something of the modern world, for example the castle being converted into a social club. What I don't like about it is the fact that the language wasn't changed from the original text. Although it is quite important to keep the film similar to the original, so as not to forget that it is the same play, I think it made the film too much like the original play. I believe that if the setting is changed, the modernisation should be completed by making the language more modern. The point of the film is, after all, to give a modern slant. The language is the most out-of-date part and the most difficult-to-understand part of the play, and I believe that modern language should have been included. I will answer the question of how the ideas have been modernised mainly by giving various examples and explanation of what has been shown in their modernisation. I will answer the question of how the beginning and ending of the play have been changed by describing both beginnings and endings, explaining the changes made and also by giving reasons for changes. I will discuss the change in theatricality by first describing the differences between what can be done in film compared with theatre, and then describing and explaining the particular changes. I will discuss the characters by giving a description of the general change in the characters, and why this is, and then by analysing the change in each character individually, with possible reasons for these changes. I will then discuss how and why the adaptation loses its social and historical meaning and adds a meaning of its own. Shakespeare plays are often modernised to make them more accessible to modern people. This is so that people now can understand the plays, and can understand the meanings behind the plays, because they have been put into a modern context that we can relate to. Some ideas are not actually just translated; they are completed changed, or some are added. For example, the idea of Macbeth being totally evil is changed. Because this modernisation is a film, which means that it has certain ways to direct the audience in a certain way, a select few of the ideas from the original play are translated. An example of these is the idea that Macduff is a complete hero. Although I do not like the fact that only a few ideas are translated, I believe that on the whole, the few that have been translated have been translated well. The beginning and ending of a play or film can be very important for the meaning behind it. Beginnings give the audience a place to start from, to understand the story. They introduce the story and characters, and give the producers a place to start the story from. Endings are useful to round off the story, and give the producers a place to end the story. They are also useful to round off the story for the audience, whether it is a resolved ending or a cliffhanger. The very beginning scene of the play involves the three witches discussing Macbeth. This gives and impression of them controlling the plot, and makes this scene seem like the original source of Macbeth's evil. The beginning of the film is very different to that of the play. Macduff says an invented dialogue, although the audience does not know who he is at the time. The beginning has a lot of subtle references to the setting and the meanings. Macduff recites the new speech on a large wasteland. When the camera first shows this setting, before Macduff enters the scene, there is nothing restricting the view, and the whole of the frame is used, including the very extremities, so there is no particular focus point. This makes suggestions about the idea of confusion and the lack of focus in the story. The fact that the camera fades in re-enforces this with a feeling of fog. This barren landscape could be a battlefield, possibly like one in the play, reflecting the war-like culture. The fact that we don't know what it is re-enforces the idea of confusion, and also the idea about the audience deciding themselves about the true meaning of the play. The shot of Macduff is very close to him, and he looks right into the camera. This gives the impression that he is talking directly to the audience. This and the fact that Macduff is in the very first scene, rather than the witches, give an impression that Macduff is controlling the whole story, instead of the supernatural. I believe that Macduff is used as part of the way that the director makes him a larger part of the story, to ask questions about his true character. There are many differences between a play and a film. The main one is that with a play, the audience can interact much more, and can decide the story for themselves. This mainly comes from lack of direction, and the ability to imagine elements of the story. One way in which this is done is by not directing the audience's view. In a film, because there is a camera, the audience's view can be directed onto a particular character or object. This means that the audience's view can also be sub-consciously directed towards a particular meaning to the film. In a play, on the other hand, the audience is free to look at whichever characters they wish, to watch their actions and reactions to other events. This adds an element of the audience being able to decide what really happens in the play, and being able to decide which ideas are true, as well as the director being able to direct the audience to parts which show their own feelings. Another way in which is this is achieved is the difference in how the setting is portrayed. A film can be shot in different locations, making the setting much more believable, and making it seem much more like the characters are in the place where they are supposed to be. One again, this allows the audience to be directed, and shown exactly what the director believes the setting is, leaving no room for imagining it. A play has a much less vivid, defined setting. It is demonstrated by symbolic references to the actual things, meaning that the audience has to imagine them more. This means that a film is better if the director wants to deliberately highlight a particular idea to the audience, and wants to tell them something that they believe in. A play is better for giving a more open story, in which the audience is independent, and decides what is true about the story. Although the setting and characters are updated in the film, the language is not. As I have already mentioned, personally, I do not believe that this is very effective, because I think that if some parts are modernised, all the parts should be, although it is quite important to keep the conversion similar to the original. Tension can be shown very well in film, by using particular camera angles or special effects. This means that the tension in the film is shown much better, which is good, but only some elements of tension are properly shown, because the director has chosen to use only certain ideas. Because of the differences between film and theatre, the audience can also be directed towards certain elements of tension. In film, visual images can be used very well, because it is a visual medium, by using special effects. I do not believe that visual effects are used to a great extent in Macbeth on the Estate. The images used are not particularly used much more than they would be in a play. I do not believe that the potential for visual effects is used fully. Instead, the film loses some of the quality of the language from the play, which is an oral medium, making the film a less effective adaptation. It may be true, though, that the director has chosen to do this because what she wants to tell us is done much more subtly by using changes in the characters and setting. The soliloquies in the film are not adapted from the play very much. No elements that are exclusive to film are used, such as visual effects, making the soliloquies very similar to the originals. This is again because the director only wanted to make subtle changes. The actor can change their character by showing different body language, for example facial expression, and can use different tones to change the meaning of what the character is saying. The way that an actor can change the character is subtle, by changing subtle things not mentioned in the script. The part can be changed in many different ways. Some of these are quite significant, such as changing the original lines, adding soliloquies and changing things that are described directly in the original script. Others are less significant, and only involve changing parts that are not directly expressed in the original script, for example set locations and body language for the actors to use to help slightly change the emotions and related things, which make up the characters. The main alteration to the characters was to make them seem corrupt and not noble, to put them and society partly to blame for everything. It is mainly the characters that are very noble in the play who are changed, to make them seem less so. The major of these is King Duncan. In the play, he was known as a good and much-loved king. In the film, although he is liked a lot by the main characters, he has lost his nobility and kingliness. Instead of his castle, he has a social club, and he is very indulgent. Although all of the characters drink and smoke, he does these to more extent, and he almost never seen without a pint of beer. As well as having un-noble habits, he is also quite a sleazy character. For example, he hassles Lady Macbeth and is unpleasant to some of his servants. He is the main element in the way that the new director shows the environment around Macbeth as being corrupt and his character is changed more extremely than the others, in this way, because he is seen as the figurehead of the nobility in the play, being the most noble. Duncan's son, Malcolm, seems to be changed to also reflect the corrupt environment, but not as much. As in the play, he does what his father does, and copies him, but this is different in the film. He joins in with the indulgence, but this could just be the result of the world around him. Like in the play, he is quite good-natured, and a good person. The director could have used this to make suggestions about young people, not just now, but always, compared to adults. I believe that the fact that she shows the young people joining in with what the adults are doing, implies that they copy what the people around them do, and they quickly become just like the rest of society. The fact that he is a good person, and is not like his father suggests that people are born good and not corrupt, though, and are not like their environment until it indoctrinates them, and it becomes normality to them. This is one of the suggestions that the director makes about society that is true about today and Shakespeare's day. Donaldbain rarely appears in the film, and he is only slightly changed, in the same way as Malcolm. Banquo is changed much in the same way as the other people around the royalty; he has also lost nobility and is part of the corrupt society. Fleance remains more or less the same as in the play, but he has more of an element of innocence. He is younger than he seems to be in the film, and he has a very close relationship with his father, relying on him heavily. He seems to be very distressed by the events in the story, and there is strange thing at the end of the film: he points his hand at the camera as if it is a gun, and fires. This could be to show that he has been indoctrinated by the corrupt society, and he is no longer fearful of firing a gun, and killing someone, because Macduff shot Macbeth. I think that he could symbolise the pure good in the story which struggles to survive in the terrible environment, and then in the end has to give up and be lost into the corruption. Macduff is changed the most in relation to the other characters. In the play, he is Scottish, like most of the other characters, meaning that his background does not make him stand out from the others. On the other hand, in the film, all of the other characters are changed into English people from Birmingham. He, on the contrary, is from the West Indies, and so stands out from the other characters due to his background. This is to make him more obviously a very significant character in the story. The director has done this because she wants to portray Macduff as more of a main character than in the film, and wants to ask us about whether or not he is really as heroic as he is shown as in the play. This was because the film explores the good and evil in all of the characters more than in the play. In the play, Macduff was very blatantly shown as a purely good character, though in the film, we are made to question ourselves about whether Macduff is really as honourable as he might seem. The director probably did this because she wanted to show that there can be evil in everyone, and no one is either pure good or pure evil. Making Macduff stand out more helps illuminate what she wanted to convey to the audience. Lady Macduff is one of the characters who has been changed relatively little: in the play, she is quite a good person, and does not have too much character that is shown; also in the film she has little character shown, other than her kindness and motherliness. Although she joins in with the corrupt society a bit, she only does to moderation, and seems quite innocent. I believe that this was because the director did not want to dilute her messages, and the characters that could not help her portray her messages and did not have much significance were kept quite bland, so as not to take away the focal point from the more important characters. The innocence may have slightly helped a suggestion of feminism. The three witches are changed a lot from the film: they have become three children. I believe that the director chose to do this to help her argument about the corrupt society; she implies that they may not really have any powers, and they just cause the characters to believe in the supernatural, and so carry out the predictions themselves. This implication can be valid to show that today's society is corrupt, and may have changed since Shakespeare's time, but it could also be used to disagree with Shakespeare, and accuse the supposed supernatural occurrences of his day on the general nature of people. Lady Macbeth is one of the few characters that have had less blame put on her than in the play for the events in the story. The audience is made to feel sympathy for her, unlike in the play, which is done in a number of ways, for example by inventing something about some lost child. The changes to her are all part of the general trend that the characters' personalities are diluted into being partially good and partially bad, to make everyone, and our society, to blame for the events. I believe that the director very strongly and effectively puts across this message, and makes Lady Macbeth seem more innocent very well. This also suggests a hint of feminism. There seems to be a hint of feminism in the conversion because the female characters are shown as much more innocent that the male characters, but it is not a very strong hint. Macbeth is also relieved of some blame. In the play, he was portrayed as a thoroughly evil man, and his evil deeds were blamed solely him or the witches controlling him. He is also part of the suggestion that society creates evil, and just does what he does because of his society. The characters are mainly changed to help put across the message that the director wants to give the audience about the story. She wants to imply certain things about the individual characters, but she also uses this to give a new impression about society. Although she wants to make implications about how today's society, and how it would change the situation in the story, she may also want to make implications about timeless aspects of society that have always existed, and possibly to disagree with Shakespeare about how society was then. Although Shakespeare made a great deal of suggestions about society, I think the new director has taken the story further, and made new ones, as well as making alterations and her own touches to the original ones. Although the film seems quite bland and without many of these meanings at first, and it is difficult for the audience to realise these subtle messages when first seen, I think that she has been very successful in showing us her personal feelings about the play and in making suggestions to us about society, as long as the audience can pick them up. Any modernisation of the play inevitably results in the loss of some of its social and historical significance. This is because to understand what is meant by the play, people would need to know what the world was like at the time, and what was happening. When a play is modernised, it stops being about that world, and is about the modern world. There are a lot of modern issues in the film. Some of these are similar to those found in the original play and are only modified, and some are completely new, and are just relevant to modern life. An example of one which is only modified is the violence. The film shows that violence still exists, but in compliance with the idea of there being no nobility, the fighting is changed into dishonourable gang warfare. The modernisation is equally as much about the original play and modern society. Most of the messages behind it concern both in different ways. The best example of an idea, which complies with both, is the idea of no nobility. It works to do with the modern world because it could imply that the nobility is lost, but it could also imply that it never existed, and the people in Shakespeare's time were just as bad as now. My argument is mainly about how the director has used lots of minor alterations to tell us of her opinion of the original story. I believe that she has used the modernisation to make it easier for modern people to understand, but also as a tool to suggest that what Macbeth does is not entirely the fault of the people who were seen as completely evil before. I think she was very successful in taking Shakespeare's meanings on further, and developing new, separate ideas, as well as some contrasting with him, for example, not showing the main characters as completely good or evil, which I believe adds a very good personal touch to it, and shows very subtly, yet effectively, her personal beliefs. The main ideas I believe she wanted to put across are: nobody is completely to blame; everyone has no evil and some good; a hint of feminism; the world of Shakespeare's time exists with us today; there could be other possibilities of why the events in Macbeth happened, that Shakespeare did not include. I think that the film can be appreciated on many different levels: as a simple modernisation for easy understanding, and also as a subtly constructed message about the personal feelings of one person, which can be enjoyed by the observant audience, and can also prompt us to think about what we think about the story, and to wonder what it is really about.

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INCREMENTAL SHEET FORMING ( Mechanical Engineering ) - Essay Example The manufacturing process is desirable for mass production because of the shared value of dies and punches with production of a large number. The performance of film forming distinct rolls to achieve a particular image was done in the past. This process is known as sheet metal rolling, but the process is possible for production of natural shapes. Therefore, the search for new sheet metal forming solutions has been started. The developments took the route of searching for new shapes of rolls, which in turn paved a way for new forming scopes. (Mecanica 2009) However, in a severe world industrialization competition, there is the need to obtain the demand for increasingly complex shapes. For the demands of complex requirements, metal plate stretching attempts have been made by outstanding prototypes, to reach the final shape. In order to contour the high volume demands, the use of presses for short lead times and production costs began. The main benefits of this method is the need for the formation of a significant essential tool for the plate formation. This increases cost of the tool, as a result of high production costs. The presses system establishment is suitable for mass production. Nevertheless, in the current global fierce competition, there is a need for more and more products that are complicated by the demand. For the achievement of the final requirements, attempts for sheet metal extension on exceptional prototype have been made to achieve the optimum shape. The formation of stretch metals on presses was adopted to handle mass production demands with more batch measurements at lower costs of manufacturing. However, the system was disadvantaged in that every product needed a specific tool, for the sheet metal development. This increases the device costs which results in higher production costs. Therefore, presses forming can be appropriate

Seaports Case Study Example | Topics and Well Written Essays - 2000 words

Seaports - Case Study Example Actually, the participation of private sector has already crept into some of the major ports in the world (Anon, 1996). The issue of privatization has gained more importance in the backdrop of globalization and liberalization moves sweeping across the world. However, the experience of the management of some ports like the Singapore port has clearly established that total privatization is not the panacea for the ills faced by several ports today. Systematic management of port operations with the public-private participation will go a long way in making them sustainable financially. There are three essential factors of a port which can be privatized; port land, port operations, and port regulations (Baird, 1999). The extent of privatization can differ within ports depending on which of these elements are transferred to private sector from public sector. We can get a wider concept from Table 1 shown below. In the private model I, port operations are transferred to private sector, and this type of arrangement is referred to as a 'landlord' port. When compared with private model I, private II model has two elements which are property and operations rights. Under the private III model, all three essential functions are controlled by private sector. At present, this kind of model is only accepted by ports in the UK, such as Liverpool, Manchester and Felixstowe. Table 1. Key Port Elements: Privatization Options Source: Baird A., 1999 International Association of Ports and Harbours (IAPH) did a survey of world's top-100 container ports to find out the organization type. Figure 1 presents ample statistics results which say that 71% of ports were managed by either public agencies or corporations, and 21% by Government departments. Only 7% of ports were private companies, and over two-thirds have a government shareholding varying from 60-100% (Baird, 2002). Figure 1. Port authority by organization type Source: IAPH, 2002 UK- Pioneer in Port privatisation Great Britain has pioneered port privatization showing the way for the rest of the world. Most countries have taken a cue from Great Britain's success in this direction. Until now, the UK is the only country which has totally privatized most of its major ports including the operational role of the port authority( ). The political leadership of the UK was very much practical in inviting private funding in port management. It always wanted to create favourable atmosphere to pave the way for private operators to jump in the fray. According to the House of Commons report, Port of London Authority strongly believed that private funding was the only alternative to refurbish the port industry and suitable and supporting atmosphere must be created to invite the private companies. It was very much worried that in the absence of a conductive atmosphere to private funding, investors might run away to some other countries ( ). The UK has obviously set a trend for other countries to follow. Most of the third world countries have also been looking for the British help in privatization of their ports ( ), such as India, Panama. Is the privatisation only solution Most of the third world countries plan to privatise their ports. But, is privatisation the only real solution Management of ports is very complex and involves several

Comment on the various sorts of love shown in Romeo and Juliet Essay Example for Free

Comment on the various sorts of love shown in Romeo and Juliet Essay Shakespeares Romeo and Juliet is a romantic tragedy based around a pair of young lovers. The play is set in 12th century Verona where a pair of families, the Capulets and the Montagues have been feuding for many years. The play revolves around Romeo Montague and Juliet Capulet falling deeply in love and the events that befall these two forbidden lovers. The play covers an array of different types of love and love related issues from brotherly love to bodily lust, Shakespeare uses the characters to portray stereotyped ideas of love and how it affects people. Before even the first scene is out, the play has already touched upon the idea of brotherly love. Benvolio, the cousin of Romeo, finds Romeo in a state of near depression and says to Romeo What sadness lengthens Romeos hours? With this line Shakespeare is showing Benvolios concern as a man might unto his brother. Romeo is sad because he has fallen in love with a girl, Rosaline In sadness, cousin, I do love a woman. However Romeos chosen spouse does not return the affection, as Romeo states She will not stay the siege of loving terms. Benvolio offers to Romeo the idea of looking for a different more attainable woman. He gives this advice in order that his cousin may once again be happy thus showing his affection for Romeo. Throughout the play Shakespeare writes about light when referring to love, he talks of it in the prologue before the play is even afoot A pair of star-crossed lovers take their life; It does not stop here however, on Romeos first encounter with Juliet he says O she doth teach the torches to burn bright Meaning that she brings light to his dark troubled state of mind, where there was the haze of rejection her light shines through brightening his mood. Again in scene two upon meeting with Juliet his love Romeo compares her presence to light But soft, what light through yonder window breaks? To Romeo meeting Juliet is like the sun rising, just as the sun lights up the world she lights up his mood and, as the sun clears the morning mist, so Juliet clears the fog of his mind leaving it clear. I think Shakespeare uses these references to light to show that in dark times often love can show the way. Perhaps showing that in the face of a problematic social environment love can be a beacon to those who embrace it. When Romeo first visits friar Lawrence in Act two Scene three they speak of Romeos newfound love for Juliet and change of heart to Rosaline With Rosaline, my ghostly father? no; I have forgot that name, and that names woe By this he is telling the friar that he has not only stopped doting on Rosaline but, has in fact undergone a total change in spirits forgetting the woes he had over Rosaline. However the Friar speaks of the doubts he had for the sincerity of Romeos love for Rosaline in the first place Thy love did read by rote, that could not spell. This implies that Romeo, whilst sounding outwardly convincing lacked the meaning behind his words. Shakespeare is again using a characters opinion to influence that of the audience, in this case Romeos love for Rosaline may well have been true but due to the friars opinionated speech the audience is cast into doubt on the matter. The friar also chides Romeo about his use of elaborate metaphorical language when talking of love, telling him to be plain, good son, For in order for Friar Lawrence to absolve Romeo he must first be able to understand him. Yet it is not just the friar who is suspicious of Romeos decorative words, Juliet had already commented on the way he talks in Act two Scene two O swear not by the moon, thinconstant moon, That monthly changes in her circled orb, Lest that thy love prove likewise variable. Romeos allegorical promises do not hold well with Juliet because in his words no definition can be found merely elaborate metaphors. However Juliets complaints go unheeded for later Act two Scene six Romeo is again using exotic language in order to describe his love for her Unfold the imagined happiness that both Receive in either by this dear encounter. Juliet however responds by saying Conceit, more rich in matter than in words, Brags of his substance, not of ornament; They are but beggars that can count their worth, But my true love is grown to such excess I cannot sum up sum of half my wealth. What Juliet is saying here is that unlike Romeo she cannot sum up her love for him in words. Shakespeare uses strong negative imagery such as beggars and conceit to display Juliets exasperation with Romeos continuing usage of needless ornate speech. But despite Juliets doubts and Romeos misleading words there is an overwhelming love between the pair that cannot go unnoticed. Even upon their first meeting Romeos feelings for Juliet are obvious Did my heart love till now? He directs this phrase at Juliet before the two have even met. Yet when they do at last meet Juliet shares with Romeo not one but two kisses, the second induced by Juliet Then have my lips the sin that they have took These shows of affection in the time in which the play was written would be unheard of upon a first meeting. This shows just how the pair truly epitomise the phrase Love at first sight for they did not let the fact that they were total strangers hinder the strength of their feelings even if the feeling was simply lust. However as of yet we cannot tell whether Romeo is sincere in his love this time rather than just lustfully infatuated as he was with Rosaline, the cousin of Juliet. However he proves himself later in the act by saying Call me but love, and Ill be new baptised; Henceforth I never will be Romeo By this he is offering to change his name if it would make Juliet love him and be with him. During Shakespearian times it was no small feat to denounce ones name, there was a lot more weight placed upon names back then, especially if it was a name of high social standing as was Romeos. This proposal shows the true and serious nature of Romeos newfound love. However it is not simply Romeo who makes such a bold offer for earlier in the scene Juliet says be but sworn my love, And Ill no longer be a Capulet To the audience Shakespeare was writing for this selfless act on both their parts would have convinced the audience that their love was true. Another factor that Shakespeare played upon to influence his audience into believing that Romeo and Juliets love was true was his use of Religious language upon their first meeting. If I profane with my unworthiest hand This holy shrine, the gentle sin is this, My lips, two blushing pilgrims, ready stand To smooth that rough touch with a tender kiss. Shakespeare deliberately uses this language to symbolise a number of things. Firstly that Juliet like a shrine is untouched or virginal this theme is recurrent through the first two acts of the play. Secondly it However not all Shakespeares examples of love are so romantic for instance Juliets mother The Lady Capulet says to Juliet considering the offer of marriage from Paris So shall you share all that he doth possess, By having him, making yourself no less. This shows a very materialistic side to Lady Capulet it also implies that the reason she is married to Lord Capulet might not necessarily be because they are in love. It portrays a much more dutiful love between Juliets parents perhaps Lady Capulet loves Lord Capulet simply because they are married rather than being married because they are in love. This type of relationship was common in Tudor times because often romanticism was overlooked in the face of bettering oneself financially. Paris show of affection for Juliet is not without a sense of duty he, as was proper in those days, approaches Lord Capulet for his daughters hand in marriage But now, my lord, what say you to my suit? At this point Capulet believes his daughter to be too young for marriage yet he encourages young Paris to woo her in order that she may fall in love with him down the line And too soon marred are those so early made. Might be referring to the marriage of himself and lady Capulet that has now become loveless and hollow. He as a loving father does not wish this upon his own only child so through Paris persistence Shakespeare shows another form of love, the love of a father for his daughter. Yet not all Shakespeares characters believed in such an honourable love. In his opening scene there are two servant men talking between themselves, there speech although on the topic of fighting generally is rife with sexual innuendo and pun. For example Ay, the heads of maids, or their maidenheads, take it in what sense thou wilt This line seemingly innocent to the reader of our time has a very rude meaning in Shakespearian language where maidenhead means virginity, in this sense the two are talking of having sex with virgins, more than a little less noble than the good Paris. They speak also of pushing women to the wall because of their weaker build; this all shows little true emotion and a very physically sexual type of love if indeed it can be referred to as that at all. Shakespeares Romeo and Juliet was a revolutionary piece when it was written because it showed just how love can move people in an age where marriage for social or financial gain was the norm. Over nearly five hundred years Shakespeares language and story line has captivated the hearts and minds of generations of lovers with its unique mixture of reality and fantasy. Romeo and Juliet is one piece of Shakespeares work that will remain a true timeless classic.

The Sherlock Holmes Essay Example for Free

The Sherlock Holmes Essay Sherlock Holmes stories were first published in 1887. The author Sir Arthur Conan Doyle was a Scottish author and physician; he wrote 4 novels and 56 short stories that included the character Sherlock Holmes. Sir Arthur Conan Doyle claims that the stories were inspired by a man he once worked for at the Edinburgh Royal Infirmary call Dr Joseph Bell. Other than Sherlock Holmes, Dr Watson plays a main part in the majority of the stories, playing the part of a friend, colleague, and side-kick. Many of the stories are narrated by Dr Watson, who was shown to keep written records of the cases. Sherlock Holmes was a well-known detective in Victorian England; this means that all of his stories contain great mystery and suspense, both great qualities to hook any audience over the many years. The mystery is portrayed taking several different angles into the stories. The most common frame of mystery is the person who appears at the beginning of the story asking for help: A lady dressed in black and heavily veiled, who had been sitting in the window rise as we entered, this quote from The Adventure of the Speckled Band is similar to quotes found in many of Conan Doyles other stories, dark figures, hiding identities and appearing at inconvenient times of the day are all aspects that regularly play part in the opening of the story. These types of openings are well written to encourage any reader into questioning who the strange person is and what has caused them to ask for help. The character of Sherlock Holmes is a strange one, who always manages to impress you with his great intelligence and ability to think out side the box. He is shown to be very observant by noticing small details about people: The left arm of your jacket is spattered with mud in no less than several places There is no vehicle save a dog cart which throw up mud that way, and only when you sit on the left hand side of the driver. The way he takes in each small detail of a person or object shows to assist him in solving his difficult and extraordinary cases. Holmes attention to detail is used to amaze a reader as usually the things he points out are things that you would not usually even think about to take notice of, such as that the lady had sat on the left hand side of the dogcart. Sherlock Holmes is also shown to be a strange man in the way that whenever he has a case to solve, he refuses to sleep but instead spends his night sitting smoking on the floor, going over and over the facts and evidence in his head until he eventually works out what has happened, usually at some early hour of the morning: He took off his coat and waist coat, put on a large blue dressing-gown, and then wandered about the room collecting pillows from his bed, and the cushions from the sofa and armchairs. upon which he perched himself cross-legged, with an ounce of shag tobacco and a box of matches. In this scene Sherlock Holmes shows that he is a man who enjoys comfort and freedom, this is demonstrated by the fact he wears a large blue dressing gown, and sits himself up on a large pile of cushions and pillows. The fact he is shown to be very used to having the finer things in life shows that he is most likely to be a wealthy man, who grew up in a privileged family. For people who grew up in a not so privileged family they may enjoy reading these books, as to gain an idea of what it is like to live an upper class life. In The Man With The Twisted Lip Sherlock Holmes is found in an opium den, this was a very strange place to find him, and when Watson, notices him, you begin to question in your mind, as to weather he really is a respectable character, or whether its Watson who has got it wrong, as traditionally an opium den was used by the lower class, rougher characters. It is the unexpected twists in the stories that have helped to grip readers and sustain the popularity of the stories over the many years.

Advanced Glycation End Products (AGE) for Diabetes

Advanced Glycation End Products (AGE) for Diabetes Diabetes mellitus is a syndrome which defined as a group of metabolic diseases characterized by hyperglycemia, that result from insufficient production of insulin, or body cells poorly respond to the insulin that is produced, or both. Insulin is a hormone produced in the pancreas and secreted in the blood to maintain blood glucose in the body through enables body cells to absorb glucose, to turn into energy. If the body cells enable to absorb the glucose, the glucose will accumulates in the blood (hyperglycemia), leading to many and different potential medical complications (Harmel Mathur, 2004). Diabetes have several categories but the majority of cases fall into two categories which are type 1 diabetes mellitus and type 2 diabetes mellitus. These two types are powerful and highly independent risk factors causing coronary artery disease, stroke, peripheral arterial disease and organ damage and dysfunction including eyes and nerves (Harmel Mathur, 2004). Type 1 Diabetes Mellitus: Type 1 diabetes mellitus resulting from pancreas failure to produce insulin hormone. Person at risk of developing type 1 can be identified by doing serologic test markers that showing evidence of autoimmune destruction of beta cells (islet cells) of the pancreas which is responsible for insulin production. Type 1 diabetes is manifested in childhood and early adulthood, but can patient present at any age (Goroll Mulley, 2009). Type 2 diabetes mellitus: Patients with type 2 diabetes mellitus are prone with wide range of series complications. Type 2 is characterized by high blood glucose due to insulin resistance and relative insulin deficiency. There are 20.8 million people in United State with type 2 diabetes mellitus. Type 2 diabetes traditionally is seen in elderly people. However it is diagnosed in obese children. Many studies shows that type 2 diabetes mellitus are associated with high calorie diet, physical inactivity and life style (Feinglos Bethel, 2008). Other Types of Diabetes: There are other types of diabetes but they are less common but patients who are underlying defect or disease process can be identified in a relatively specific manner. These types are Genetic defects of beta-cell function, Diseases of the exocrine pancreas e.g Fibrocalculous pancreatopathy, Endocrinopathies and cystic fibrosis and Uncommon forms of immune-mediated diabetes. Diabetes mellitus complications: Diabetic complications can be grouped into macrovascular and microvascular disease. Macrovascular diseases are result from atherosclerosis which develops in earlier age in patient with diabetes. There are several factors contribute to atherosclerosis such as lipidemia, hypertension, increased platelets adhesion and aggregation, elevated factor V, factor VII and fibrinogen concentration. Macrovascular diseases are seen in both type one and two of diabetes mellitus and they include coronary heart disease, Ischemic stroke and peripheral vascular disease (which can lead to ulcers, gangrene and amputation) (Winter Signorino, 2002). Whereas, Microvascular complications is seen in type one diabetes mellitus. Hyperglycemia damages the basement membrane of capillaries in the retina and glomerulars which leads to retinopathy and neuropathy. Microvascular diseases include neuropathy (nerve damage), nephropathy (kidney disease) and vision disorders (eg retinopathy, glaucoma, cataract and corneal disease). Furthermore there are other complications of diabetes include infections, metabolic difficulties, dental disease, autonomic neuropathy and pregnancy problems (Winter Signorino, 2002). Several clinical research show a strong relationship between hyperglacemia and diabetic microvascular complications in both type 1 and type 2 diabetes. High glucose and insulin resistance play important roles in the pathogenesis of macrovascular complications due to atherosclerosis. Diabetes-specific microvascular disease in the retina, glomerulus and vasa nervorum has same pathophysiological features. Intracellular hyperglycaemia causes abnormalities in blood flow and increased vascular permeability which leads to decreased activity of vasodilators such as nitric oxide, increased activity of vasoconstrictors such as angiotensin II and endothelin-1, and elaboration of permeability factors such as vascular endothelial growth factor (VEGF) (Brownlee, 2001). There are several factors which contribute the formation of inflammation, atherosclerosis and diabetes mellitus complication. These factors are hyperglycemia, accumulation of advanced glycation endproducts, dyslipidemia and oxidative stress which lead to endothelial dysfunction resulting in thrombotic complications and cardiovascular (Altman, 2003). In type 1 diabetes mellitus, high blood glucose is usually as result of low level of insulin secretion whereas in type2 hyperglycemia is caused by resistance of insulin at the cellular level. Low insulin levels or insulin resistance enable the body to convert glucose into glycogen (a starch-as source of energy which stored in the liver). In type 1 diabetes, pancreatic beta cells are attacked by auto-immune which cause infiltration of inflammatory cells and increased expression and secretion of S100-calcium binding protein and high-mobility group protein 1 (HMGP1) through inflammatory cells which consequently lead to islet damage and increased blood glucose level, subsequent accumulation of AGE (Bierhaus Nawroth, 2009). Comparing to T1D, in type 2 diabetes mellitus, different metabolic disturbances stimulates inflammatory cells to secretes RAGE ligands, which cause low-grade inflammation and increased oxidative and carbonly stress, all these play roles in promoting AGE formation and RAGE expression in respective organs (Bierhaus Nawroth, 2009). Insulin resistance and Inflammation: In diabetic patients with hyperglycemia, cause by 1) impaired insulin secretion by the pancreatic ß-cells, 2) muscle insulin resistance, and 3) hepatic insulin resistance all play central roles in the development and progression of glucose intolerance. As I mention before, type 2 diabetes mellitus (T2DM) is characterized by insulin resistance in liver and muscle and impaired insulin secretion. Also include deranged adipocyte metabolism and modified fat topography in the pathogenesis of glucose intolerance in T2DM. Fat cells are resistant to insulins antilipolytic effect, which result in increased plasma free fat acid levels. Long period of increasing plasma fat fee acid stimulates gluconeogenesis, promote hepatic and muscle insulin resistance, and impairs insulin secretion in genetically predisposed patients. These pathways of FFA-induced are known as lipotoxicity. Fat cells Dysfunction makes excessive amounts of insulin resistance-inducing, inflammatory, and atherosclerotic-provoking cytokines and fails to secrete normal level of insulin-sensitizing adipocytokines. Enlarged fat cells are insulin resistant and have minimized capacity to store fat. When storage capacity of adipocyte is exceeded, lipid overflows into muscle, liver, a nd perhaps ß-cells, resulting in muscle, hepatic insulin resistance and impaired insulin secretion. In type 2 diabetics, the ability of insulin to stop lipolysis and to decrease the plasma FFA levels is markedly impaired. It is clearly that chronic elevated levels of plasma free fat acid leads to insulin resistance in muscle and liver, and impair insulin secretion. In addition to FFA in plasma, increase stores of triglycerides in muscle and liver which correlate closely with the presence of insulin resistance in tissues. The triglycerides in liver and muscle are in a state of constant turnover, and the metabolites of intracellular triglyceride lipolysis impair action of insulin in liver and muscle (Bays et al, 2004). This pathway of events has been referred to as lipotoxicity . The accumulation of lipid in dipocytes leads to activate NADPH oxidase which increases the production of reactive oxygen species (ROS). The mechanisms increased production of cytokines including TNF-ÃŽ ±, IL-6 and monocyte chemoattractant protein-1 and reduce the production of adiponectin (Shoelson et al, 2006). Furthermore accumulation of lipid activates the protein response to increased ER stess in fat and liver. All these have accumulated to induce lipotoxicity as an important cause of ß-cell dysfunction (Bays et al, 2004). Receptor for advanced glycation end products (RAGE): RAGE is type I transmembrane receptor of the immunogloblin superfamily. It is a receptor for advanced glycation endproducts (AGE). It is about 45-KD a protein and it is consist of 403 amino acids in human, rate and mouse. Its extracellular region consists of one V-type (variable) immunoglobulin domina, which followed by two C-type (constant) immunoglobulin dominas (Basta, 2004). Its name drive from its ability to bind AGE and also it is known as AGER. It is located within the major histocompatibility complex (MHC) class III region on chromosome 6, which contains numbers of genes involved predominantly in inflammatory and immune responses and several components of complements. Beside AGE, RAGE is able to bind several ligands therefore is called a pattern-recognition receptor. These ligands are high-mobility group protein 1 (HMGP1), S100-calicum binding protein (S100b) which is family of pro-inflammatory cytokines and it can be found in any inflammatory lesion and vascular walls of diabetics patients, amyloid-ß-protein and macrophage-1 glycoprotein (CD11B/CD18). RAGE plays role in diabetes and other metabolic disease. The interaction of RAGE and its ligands cause pro-inflammatory activation. It is involved in several diseases such as innate immune response, mediating immune and inflammatory response, cancer promoting and progressing and microvascular and mi crovascular diseases (Bierhaus Nawroth, 2009). Moreover, RAGE expression is increased in the cells of the vascular walls, at the site where AGEs and S100/calgranulins are accumulated, including endothelium vascular smooth muscle cells, glomerular mesangial cells and mononuclear phagocytes. This destrbution of RAGE and its ligands leads to increased cellular activation, causing further raised expression of the receptor (Basta et al, 2004). Recently the studies have been proved that RAGE and its ligands accumulate in diabetes and contribute to its pathology. Serum levels of S100A8/9 and S100A12 increased in type 2 diabetic patients. Also, evidence was provided by raised serum levels HMGB1 were linked to coronary artery disease in type 2 diabetes. In addition the studies which have been done in streptozotocin-induced diabetic rats proved that diabetes increased amyloid-beta-peptide (1-40) levels in the brain. Furthermore, CML-modification of S100A8 and S100A9 are seen in inflammatory bowel disease and promote RAGE-mediated sustained inflammatory. Moreover, Carboxylated N-glycans on RAGE eases binding of HMGB and mediates ligation of S100A8/A9 to subpopulation of RAGE on colon cancer cells (Bierhaus Nawroth, 2009). Advanced Glycation End products (AGE) and its biochemical mechanism production: There are various pathways involved in stimulation of atherosclerosis in diabetes mellitus. However the most important one is formation and deposition of AGEs through nonenzymetic reaction between extracellular protein and glucose and it accumulates within cells of the vascular walls, in the extracellular space, kidney, nerves and retina (Basta et al, 2004). Possible mechanism of AGEs formation arise from intracellular auto-oxidation of glucose to glyoxal, decompounding of the Amadori product (glucose-derived 1-amino 1-deoxyfructose lysine adducts) to 3-deoxyglucosone and fragmentation of glyceraldehyde-3-phosphate and dihydroxyacetone phosphate to methylglyoxal. These reactive intracellular dicarbonyls (glyoxal, methylglyoxal and 3-deoxyglucosone) which can react with amino groups of intracellular and extracellular proteins to form AGEs (pyrraline, pentosidine, CML, crossline) (Balasubramanyam et al, 2002). Several experimental studies evidenced that advanced glycation end products can alter vascular wall homeostasis in atherogenic through different ways which are: AGEs and mononuclear phagocytes Interaction: The binding of AGEs with mononuclear phagocytes MPs induces the activation of platelet-derived growth factor, insulin-like growth factor-1, and pro-inflammatory cytokines, such as IL-1ß and TNF-ÃŽ ±. Furthermore the interaction of AGEs with its receptor (RAGE) in the mononuclear phagocytes promotes cell migration (chemotaxis) (Basta et al, 2004). AGEs and vascular smooth muscle cells Interaction: Interaction of AGE with smooth muscle cells (SMCs) exhibits the proliferative activity and production of fibronectin. SMC growth are indirectly mediate by cytokines or growth factors which induced by AGEs in the MPs. Transforming growth factor-ß (TGF-ß) act as an intermediate factor in AGE-induced fibronectin formation by SMC(Basta et al, 2004). AGEs with vascular endothelium Interactions: alterations of vascular permeability and of adhesive properties As result its unique position and numerous properties, the vascular endothelium has important role in the regulation of extracellular permeability, the maintenance of blood fluidity, metabolism of hormones and vasoactive mediators and the regulation of vascular growth and tone. The endothelium is exposed to AGEs located on circulating proteins and cells (such as, diabetic RBCs), also those found in the underlying subendothelial matrix. Receptors for AGEs present on the endothelial cell surface, and mediate both the uptake and AGEs transcytosis, and the internal signal transduction. AGE-RAGE interaction leads to alteration of barrier function and an increased permeability of endothelial cells interact with AGEs and increased migrate of macromolecules through the endothelial monolayer. The increase in permeability is associated by alterations of the physical integrity of the endothelium, as shown by the destruction of structures and alterations of cellular morphology (Basta et al, 2004 ). Also, it has been proved that AGEs cause alterations of endothelial anti-hemostatic functions in vitro, through a reduction of thrombomodulin expression and accompanied with induction of tissue factor expression. The promoting of tissue factor and the decreasing in thrombomodulin activity change the dynamic endothelial features with regard to hemostasis from those of an anticoagulant to those of a procoagulant surface (Basta et al, 2004). Intraction of AGEs with endothelial RAGE also causes the depletion of cellular antioxidant defense mechanisms (such as glutathione, vitamin C) and the generation of reactive oxygen species. As a result of the increased cellular oxidative stress, NF-ÃŽ ºB activation occurs, thus inducing the expression of NF-ÃŽ ºB-regulated genes including, in addition to the procoagulant tissue factor, adhesion molecules, such as E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1); this past may prime diabetic vasculature towards enhanced interaction with circulating monocytes. Furthermore, the incubation of endothelial cells with EN-RAGE or S100B results in VCAM-1 induction, in a RAGE-dependent manner, as sustained by the inhibitory effect of anti-RAGE IgG or soluble RAGE (Basta et al, 2004). Alterations of endothelium-dependent vasodilatation AGEs linked to the vascular matrix may quench bioavailability of nitric oxide (NO), which is an important regulator of vascular tone inducing smooth muscle cell relaxation. Studies provided that, AGE inhibits NO activity, when it added to NO in vitro. Studies on animal exterminate induced diabetes show that an alteration of endothelium-dependent dilatation occurs in short period, within 2 months, from diabetes induction. A direct reaction between NO radical and other free radicals which are formed during the reactions of AGEs assumable leads to inactivation of NO. In parallel, advanced glyaction end products promote the expression of the potent vasoconstrictor endothelin-1 changing endothelial function towards vasoconstriction (Basta et al, 2004).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  These four mechanisms promote and alter vascular wall homeostasis. When mononuclear phagocytes migrate to the site of immobilized AGEs in the tissue, their migrations allow them to interact with AGE -modified surface and become activated. This mechanism cause attracting and retaining MPs in tissue where AGEs deposit. Migration and activation of MPs and T cells (inflammatory cells) promote and cause chronic vascular inflammation through alter vessel wall (Basta et al, 2004). Promotion of atherogenesis pathways by AGEs: AGEs are most important factors in endothelial dysfunction in diabetic patients through binding its receptor (RAGE). Advanced Glycation Endproducts stimulate the expression of proinflammatory cells and molecules (Altman, 2003). AGEs can be seriously deleterious to the function of blood vessel walls in various ways. First it causes blood vessel dysfunction through cross bridges among vessel macromolecules. Secondly of damage is that accumulation of AGEs lead circulating blood cells to adhere to the vascular walls which promote atherosclerosis. Third way is through binding different receptors which have been recognized on various cell types such as macrophages, endothelial cells, and smooth muscle cells, renal and neuronal cells (Basta et al, 2004). Hyperglycaemia Mechanisms-caused damage: Hyperglycemia diverse microvascular and macrovascular complications in diabetic patients through several mechanisms such as increased formation and accumlation of advanced glycation end-product (AGE); activation of protein kinase C (PKC) isoforms; and increased generation of reactive oxygen species (Bonke et al,2008) Increased production advanced glycation end-products AGE promote atherogenesis pathway through accumulation of AGEs and AGEs ligation to RAGE on endothelial cells and macrophages induce inflammation through activating pro-inflammatory cytokines including TNF-ÃŽ ±, 1L-6 a L-1ß, induction of reactive oxygen species (ROS) and through increased oxidative stress which lead to degradation of IKBs (IKBs is normally bound to NF-KB to prevent translocation of NF-KB to nucleus). ROS activates NF-KB which results in translocation of NF-KB to nucleus. Activation of NF-KB cause pathological change of gene expression which is highly related to inflammation, immunity and atherosclerosis, increased expression of inflammatory mediators which lead to insulin resistance and increased RAGE expression as well (Basta et al, 2004). Mechanisms by which intracellular production of advanced glycation end-product (AGE) precursors damages vascular cells. Cellular functions are altered by dicarbonyl advanced glycation end products. Alteration of extracellular matrix proteins results in abnormal interactions with other matrix proteins and with integrins. Alteration of plasma proteins by AGE precursors generate ligands that bind to AGE receptors, inducing conversion of gene expression in endothelial cells, mesangial cells and macrophages. Activation of protein kinase C: The protein kinace C (PKC) family compromises at least eleven isoforms, nine are induced by the lipid second messenger diacylglycerol (DAG). Altered DAG-PKC pathway play an important role in diabetic complications. Intracellular hyperglycaemia raises the amount of DAG which activate PKC in cultured vascular cells and in the retina and renal glomeruli of diabetic animals. Hyperglycaemia may also activate PKC isoforms indirectly by AGEs bind receptors and increased activity of the polyol pathway, possibly through increased reactive oxygen species (ROS). AGE stimulated diacylglycerol (DAG) and activate protein kinase C (PKC) in VSMC. PKC is one of important signal transduction elements involved with multiple cell response. In early studies of diabetes, retinal and renal blood flow abnormalities are due to activation of PKC-ß isoforms perhaps through depressing nitric oxide production or increasing endothelin-1 activity. Abnormal activation of protein kinase C has several pathogenic c onsequences: It leads to decreased production of nitric oxide in smooth muscle cells and glomerular mesangial cells that is induced by hyperglycemia (Brownlee, 2001). Activation of PKC causes inhibition of insulin-stimulated expression of mRNA for endothelial nitric oxide synthase (eNOS) in cultured endothelial cells. Hyperglycaemia activates PKC to increased endothelin-1, permeability of endothelia cells and increased expression of the vascular permeability angiogenesis factor (VEGF) in smooth muscle cells (Brownlee, 2001). Increased generation of reactive oxygen species: Increased generation of reactive oxygen species (ROS) is another possible pathways of diabetes complications especially nephropathy complication. Production of Reactive oxygen species can be result from the activation of various enzymes, including NADPH oxidase, nitric oxide (NO) synthase, and myeloperoxidase, with arising evidence that NADPH oxidase is the major cytosolic source of ROS generation in diabetes. NADPH has homologues that are present within the kidney, namely nox-3, seen in fetal kidney, and nox-4, which is predominately expressed in the renal cortex. AGE bind RAGE induces signal transduction and activate NADPH oxidase in endothelial cells. The interaction between AGE-RAGE enhances production of the cytokine vascular endothelial growth factor (VEGF), which is directly induced by NADPH oxidase and is associated with the pathogenesis of albuminuria in diabetes (Bonke et al, 2008). Diabetes mellitus control and treatment: Both type 1 and 2 diabetes mellitus are characterized by elevated blood glucose level due to insufficiency of insulin level. Therefore, diabetes patients need to reduce blood glucose level through healthy diet, drugs such as (hypoglycemic tablets and anti-atherosclerosis drugs), insulin injection and regular physical exercise. Healthy Diet: In general, healthy diet for diabetes patients should include: limit fats (especially saturated fats and trans-fat acid), proteins and cholesterol. Also, patient should consume a lot of fiber and vegetables. Patients with insulin-producing or insulin synthesis treatment should monitor their blood glucose level to avoid hyperglycemia. For example, adults and teenager patients should maintain their blood glucose level between 80-120 mg/dl, and 100-200 mg/dl for children under 12 year old. Type 1 diabetes patients should test their blood glucose level four to more per day. However, in type 2 diabetes, patients recommend to measure blood glucose level 1 to 2 times daily, because glucose level in type 2 diabetes is more stable than in type 1. Such important tests are important during diet plans and treatment. For example, glycosylated hemoglobin test (HbA1 c) is an indicator for carbohydrate level. Micro and macroalbuminuria indicates of the proteinuria and renal function, for instance if the teat showed high level of proteinuria then the patient need to lowering protein intake (Flaws et al, 2002). Exercise: Physical exercise is important to manage diabetes complications. Regular exercise improves the status of both type 1 and 2 diabetes through transporting sugar to muscles, improving blood circulation, and increasing insulin receptors. Exercise has specific effects on diabetes patients include: reducing blood glucose level during and after exercise, increased insulin sensitivity, reduced triglyceride level and increased good cholesterol (HDL) (Flaws et al, 2002). However, diabetes patients may have several risks associated with exercise which include: hypoglycemia if patient under treatment with hyperglycemia agents, hyperglycemia and ketosis in insulin-deficient patients, and exacerbation of cardiovascular disease. Therefore, patients who are over 30 year old should be examined before doing physical exercise. These examinations include: cardiovascular exams such as blood pressure, blood lipid and ECG, and neurological evaluation such as eye exam (Flaws et al, 2002). Anti-inflammatory drugs Various drugs in recent clinical practice have been used as anti-inflammatory agents such as thiazolidinedione (TZD) class of PPARÃŽ ³ agonists and members of statin class of HMG CoA reductase inhibitors. Both of them have importane anti-inflammatory properities and both have action on glucose homeostasis and cholesterol redusing (Shoelson et al, 2006). TZDs are used to induced insulin sensivity and decresed hyperglicemia in patient with type 2 diabetes mellitus. TZDs drugs inculde pioglitazone, rosiglitazone and troglitazone. The role of TZDs is through binding and activiting PPARÃŽ ³ to induce a number of gene expression products in a dipocyte. TZDs action are attributed to fatty acid in the a dipose tissue. TZD decreases circulating free faty acid and keep faty acid out of musle and liver because accumalte of fatty acide in these tissue lead to insulin resistance. In addition, PPARÃŽ ³ is not only present in dipocyte but also in it is expressed in macrophages and other immune cells response, hepatocyte, endothelial cells and vascular smooth mucsle cells (VSMC). TZD play role in reduce the expression of targets gene for cytokines, growth factors, proliferation and migration of cells, and cell cycle progression (Shoelson et al, 2006). Rosigliatozone: Rosigliatozone decreses the inflammatory markers such as serum C-reactive protein, metalloproteinase-9, white blood cell, tumer necrosis factor-ÃŽ ± and serum amyloid-A in type two diabetes mellitus (Altman, 2003). Group of studies done on Diabetes Rodents: The recent research has demonstrated that rosiglitizone, a PPARÃŽ ³ agonist, attenuates diabetes associated atherosclorosis. The reaserch has studied the direct antiathersclosis effects of PPARÃŽ ³ afer long beriod of therapy in an experiment of insulin deficiency. This study show that rosiglitezone has no effect on glucose level in both control or diabetes mice. However, rosiglitizone , PPARÃŽ ³ (acting as insulin sinstiser) significally decresed plasma insulin level in control mice (Calkin et al, 2005). In addition to Calkin study and his collegous, another study shows that rosiglitazone increase the insulin content and iselt cells number and total mass of pancreas in diabetes rats. However, it is unknown if this is adirect effect of rsiglitazone by activation of PPARÃŽ ³ mediated pathway in islets or indirect effect of normalizing the hyperglicemia (Sanchez et al, 2002). Increaesd secration rate of proinsulin relative to insulin is one oa acommon feature in type 2 diabetes mellitus. The normal range of proinsulin in normal subjects is about 2 to 4% of the total amount of insulin and in type 2 diabetes proinsulin rate is about 15%. Curently the studies has been demonstrated that rosiglitazone in type 2 diabetes decrease proinsulin secretion. Proinsulin has been associated with activity of carboxypeptidase E. Fricker and collegous have evidenced that carboxypeptidase are present in secretory pathway and participate in peptide processing. CarboxypeptidaseB has similler feature as carboxypeptidaseE but the precursor sequence of carboxypeptidaseB has been seen in an adult mouse islet cells. Thus suggest that rosiglitazone may has primery effect on increasing the expression of carboxypeptidaseB precursor protein resulting in increse proinsulin to insulin conversion (Sanchez et al, 2002). Further more, rosiglitizone did not affect fasting insluin level in diabetic mice due to streptozotocin which induce insulin insufficency. Also, another group of study has curently demonstrated that short period of treatment with rosiglitizone decreased plaque area in diabetic mice but had no determination if effects seen were linked to insulin sensitization (Calkin et al, 2005). More current sutdies have evedanced that rosiglitezone treatment in diabetes mice reduce gene expression of the NF-KB subunit p65. Further study has shown that rosiglitizone has no direct effect o glucose-induce upregulation of oxidative stress. Same study had investigated RAGE expression acording to preveious finding that first of all, RAGE expression increse oxidative stress and secondly rosiglitezone which used in culture media alter RAGE expression. The study had shown, the expression of RAGE gene wasnt altered by rosiglitizone (Calkin et al, 2005). Some study showed no significant alteretion in gene expression after TZDs treatment. This is because of almost studies were not preformed in human adipose tissue in vivo but they used adipose tissue of rodents and adipocyte cell line. Actually under such study we should consider about some facts that, for example rosiglitazone dose which used in rodents study (10 mg/kg) is higher than human dose about 100-fold. furthermore, TZD may has an action on gene expressed in rodents but it is not necessarily to has same action on human gene. For example carbonic anhydrase 3 protein raised 2-fold after treated the mice with rosiglitazone, however there was no increasing in carbonic anhydrase 3 mRNA in human adipocyte. Although there were similarities in the action of TZD-induced insulin sensitivity, there may be TZD action has different mechanisms on experimental models and human (Kolak et al,2007). Therfore, Im going to discuss about the studies which have been done on human adipose tissue and there findings. Group of studies done in human patient with type 2 diabetes: Overactivity of ubiquitin-proteasome system is associated with the inflammation and atherosclerotic plaques in type 2 diabetes. Study by Marfella and his colegous on human diabetes patients has been shown that the PPAR-ÃŽ ³ agonist rosiglitazone reduce ubiquitin-proteasome activity and thuss prevent plaque progression to unstable phenotype in diabetes individulas (Marfella et al, 2006). Also, same study shows, the production of O2- by monocytes is reduced after rosiglitazone treatment. Thus proteasome reduction is induced by inhibition of oxidative stress and polyubiquitination. As oxidative stress induce insulin resistence through NF-kB activation, rosiglitazone enhance insulin sensivity and plaque stability in diabetes patien through reducing oxidative stress and ubiquitin-proteasome activity. Further possibility that, NF-KB activation is inhibited by rosiglitazone through a PPAR-ÃŽ ³ independent pathway. PPAR-ÃŽ ³ agonist inhibits NF-KB translocation and subsequent DNA binding through inhibits immune response which induce degradation of IKBs (Marfella et al, 2006). Rosiglitazone have significant effects on metabolism of faty acid and lowering circuliting non-esterified fatty acid. Therfore rosiglitazone prevent islet cells through reducing fatty acid exposure (Sanchez et al, 2002) Kolak and his colleagues investigated the gene of expression in human adipose tissue in vivo in type two diabetes mellitus, befor and after tratment with rosigliatozone and metformin. Reosigliatozone modulates expression of gene which involved in free faty acid synthesis and storage, protein strcture, inflammatory cells inculde macrophage and gene associated in glucose transport and insulin sensivity. Whereas metformin has no effect on these gene (Kolak et al, 2007). TZD decrease the expression of RAGE endothelial protien. From preveious finding, TNF-ÃŽ ± increase the expression of RAGE on endothelial cells, so

Four Sides of Shakespeares The Tempest :: Tempest essays

Four Sides of The Tempest 1 "They all enter the circle which Prospero had made, and there stand charm'd" In the First Folio edition of The Tempest, at the climax of the action, Shakespeare instructs that the magician Prospero inscribe a magic circle on the bare Elizabethan stage into which all the various characters of the action will be drawn: sage and fool, monarch and savage, clown and lover, young and old, cynic and innocent. It is as if Shakespeare, through Prospero, has assembled a representative sample of divided humanity, and brought them together deliberately to re-enact the oldest of rituals and the most insistent themes of history and of psychology The divisions among these characters resonate deeply, with many implications. They have been elaborated in generations of Western thought: together with Prospero, the spirit Ariel and the grotesque Caliban have been "read" through such critical lenses as Thomas Aquinas' division of human nature between spiritual and animal elements, or Darwin's evolutionary ladder, or Freud's superego and id,or through images of colonialism, or Jung's conflation of history with psychology, in which "our world is dissociated like a neurotic." In such a view, the reintegration of fractured family and society that takes place in this play is at the same time a reintegration of the divided and conflicted self into health and wholeness. In Georgia Shakespeare Festival' s The Tempest, the circle on the stage floor, the Shakespearean sign of wholeness, is the Jungian symbol of the "Quaternity of the Mandala,"a square-within-a-circle that was a symbol of the resolution of opposites and a sign of the transformation of both individual and collective consciousness, the full promise of human potential. Thus, when Prospero, having chosen the road of reconciliation over that of recrimination and rejection, draws the rapacious and rebellious Caliban into the magic circle, only to say of him "This thing of darkness I acknowledge mine," we seem for a moment to pass beyond the logic of power and punishment into a higher, more inclusive awareness. The magician who will shortly surrender his powers, sees and acknowledges the brutish side of himself, his own abjection, power-lust, possessive-ness, and scheming resentment.

Walter Lippmanns The Public Philosophy :: The Public Philosophy

Walter Lippmann's The Public Philosophy   Ã‚  Ã‚  Ã‚  Ã‚  Walter Lippmann begins his The Public Philosophy by expressing his concern for the state of the Western Liberal Democracies. The West, he writes, suffers from "a disorder from within." This disorder has its roots in the long peace between 1812 and 1914, and was further exascurbated by the great population increase of that era and the coinciding industrial revolution. The latter changed the nature of armed struggle, which in turn intensified the "democratic malady." The situation Lippmann describes is the "paralysis of governments," the inability of the state to make difficult and unpopular decisions.   Ã‚  Ã‚  Ã‚  Ã‚  This paralysis is the product of both the long peace and the great war. The period extending from Waterloo to 1914 lulled the West into believing that the age of Man's aggression had passed. Because the "hard decisions" of taxation, prohibition, and war were not often faced in these years, the Jacobin concept of the desirability of weak government was instilled in the West. When the first world war did come about, the West was unable to deal effectively with its costs. The new technologies spawned by the industrial revolution, as well as the greater populations involved, had made war infinitely more costly than in the past. Consequently, the executive aspects of Western governments were forced to "democratize" the appropriation of men and money by handing their power to the representative assemblies. The assemblies too were forced to cede their power to "the People," who channeled them to media powers and party leaders. The result was "Disastrous and revolutionary . The democracies became incapacitated to wage war for rational ends or to make a peace which would be enforced."   Ã‚  Ã‚  Ã‚  Ã‚  Lippmann holds that the major malfunction of the West is this acquisition of executive and representative powers by the masses. This is a fundamental distortion of the rights of the governed. Lippmann contends that the People have but two natural rights: to decide whether or not to by governed, and to choose who shall govern them. "This breakdown of the constitutional order is the cause of the precipitate and the catastrophic decline of Western society."   Ã‚  Ã‚  Ã‚  Ã‚  Why then, cannot a mass govern effectively?