Financial Contracts in Islamic law compared to that of American Law Dissertation

Financial Contracts in Islamic law compared to that of American Law - Dissertation Example Financial contracts can be entered in both written and verbal formats and must be discussed and accepted during a single meeting without any noticeable interruptions including multiple negotiation sessions or changes in the meeting venue. Unlike provisions under American law, Islamic financial contracts can be accepted based on personal conduct of the parties (Hassan, 2007). Under special circumstances, non-responsiveness to a given contract proposal is taken as an acceptance. Islamic law also allows further flexibility among parties within a given meeting session whereby parties have the right to refuse a contract up to the point when either party leaves the meeting venue physically. However, variations do exist over the interpretation, implementation and recognition of this feature even within countries where Islamic finance is practiced (Vogel, 2008). Contents of the financial contracts under Islamic law are prohibited from discussing or relating with any item prohibited by the re ligion. Such substances include alcohol and tobacco besides prohibition on gambling. All applicable items that constitute the contract content must further be in the possession or ownership of either party and legally exist at the time of the initiation of the contract (Rayner, 2001). In simple words, items that will be devised in the future may not be included in an Islamic contract. Specific properties of all these items including specifications, origin and quality must be clearly states in the terms of the contract. Other than deals that involve the exchange of money, the exact price at which the goods will be delivered should be agreed upon prior to contract agreement (Hassan, 2007). Contracts based on future prices that are speculative in nature are not allowed and cannot be developed based on the advice of a third party. While there are several types of Islamic financial contract, the most common one that is used for sale and exchange of goods is known as mu’awadat. Goo ds can be sold either for money or can be exchanges as part of a barter transaction. Even exchange of money is valid under Islamic contract. Real estate or equipment can be leased to external parties by using another type of contract known as the ‘ijara’ (Vogel, 2008). The concept of Islamic contracts has been in existence for several centuries in regions like the Middle East, Asia and North Africa where Islam continues to be a major religion (Ayub, 2009). Islamic finance is considered as a tool from the almighty and is based upon relevant Islamic principles that place a high value on moral principles that is expected of all followers of the religion. Conventional American law is aimed at helping create contracts that are ‘ethical’ in nature. Islamic finance advocates a similar approach when developing contracts and related transactions. However, this feature must not lead to an assumption that Islamic contracts bear a close resemblance with Western contrac ts (Rayner, 2001). In fact, contracts agreed upon under Islamic law are rather less binding than conventional American contracts that imply all aspects covered under them. Legal advice and further scrutiny is thus necessary in the case of Islamic contracts to understand the circumstances under which a contract may not be valid. In addition, the application of Islamic contracts has not been uniform across the Islamic world. While countries like Pakistan and Iran apply Islamic law in a stringent fashion, other countries

History of Electronic Media Essay Example for Free

History of Electronic Media Essay The history of providing information has been shaped by innovations and innovators. This paper attempts to chronicle the different factors and events that led to the media landscape of today. 1) Congress and the FCC began deregulating broadcast and cable television in the late 1970s. Describe the ideologies which motivated these deregulations. What changes in the television industry occurred as a result of these deregulations? Include two of the following in your discussion: Financial Interest and Syndication Rules, Telecommunications Act of 1996, media ownership debates in the 2000s and intellectual property regulations in the 2000s. The Financial and Syndication Rules, or more popularly known as Fib-Syn, were implemented by the Federal Communications Commission in 1970 with the objective of increasing programming diversity thus breaking the monopoly of the three major TV networks in the United States: CBS, ABC and NBC. Its rationale was to democratize UHF airwaves making it easier for independent television producers to penetrate the television market. The rules primarily targeted two areas to disempower the big networks: freeing television programs from the ownership of the networks after its first run and the introduction of in-house syndication arms in the major networks. The idea was to discourage the networks monopoly on tv programs and restricting the networks part in syndication. These steps would substantially reduce production incentive and lead to the separation of production and distribution practices in the big networks. The FCC justified the implementation of Fin-Syn as beneficial for independent television producers since it gave them the larger part of production profits and allowing them a foothold in the business of syndication. The democratization of syndication would lead to a wider distribution of shows and prevented the networks from its exclusive use in their affiliated stations. Supporters of the rule envisioned a television industry where innovative and   much more diverse programs would be available to the viewers ( McAllister , www.museum.tv). The Telecommunications Act of 1996 was promulgated by the FCC to address issues regarding the rapid development of telecommunication technologies in the United States. It contained new rules and regulations regarding TV, Radio, Cable, Telephone and Internet services. President Clinton, when he signed it into legislation, proclaimed that the act would â€Å"stimulate investment, promote competition, provide open access for all citizens to the Information Superhighway† (Clinton, White House press release 1996). Upon closer inspection, the Telecommunication Act of 1996 was the final step in disassembling the provisions of Fin-Syn Rule. The act loosened rules on media ownership in traditional media forms such as TV and radio, thus empowering them to compete with emerging media technologies such as cable and the Internet allowing for the development of new and innovative services. However, the implementation of both the Financial and Syndication Rules of the FCC and the telecommunications Act of 1996 met harsh criticisms once they were fully implemented. The introduction of Fin-Syn bred more problems than solutions. Most critics pointed out that instead of empowering independent TV producers, it just shifted the competition from one Goliath to another. Instead of   competing with the big networks, the independent TV producers where now pitted against large production organization such as Disney/ABC and   Warner. In the end, it was these larger TV production companies that benefited financially from producing television shows with independent companies opting to produce cheaper productions such as talk shows and game shows. Thus, it produced more conventional shows rather than innovating the television industry. Eventually, television groups especially television distributors called for a change in the implementation of Fin-Syn which eventually led to FCC totally removing the rule in 1995. Studies showed that although there were periods of diversity on TV programs from 1970s to the 1990s, the general conclusion was that there was no significant changes in the programs in the implementation of the FCC rule (Einstein, p. 5). With the disappearance of the rule, productions and distribution companies started to merge especially in the big three networks. This culminated in the emergence of FOX Network and its merger with Paramount and Warner Bros., a step followed by Disney when they bought and merged with ABC Network. The deregulation that resulted from the implementation of the 1996 Telecommunications Act fueled much debate on media ownership and responsibility. Questions arose on whether the the Act did deliver its promise of innovative media services from increased competition and serve the public interest with increased diversity in media programs and information. Critics cite that the only ones who benefited from the Act were media moguls who were able to merge with other media corporations and in essence creating media monopolies that could have the power to control information. William Melody reveals that media entrepreneurs will always look for profit and economic efficiency leading to media monopolies which threaten freedom of speech (Melody, p. 32). Concerned groups have also reasoned that public interest have always been the core value of media regulation and not profit, and to diminish government control on ownership would mean violating public inters. Deregulating media ownership can only lead to a monopoly of information resulting in less diversity, Neumann noted that the creation of media conglomerates have led to the mass media having similar â€Å"content and world-view† (Neumann, p.130). On the other hand, those who were in favor of the Act identified it as a much needed move in revolutionizing media. By allowing media corporations to merge, it has led to a more comprehensive and cohesive delivery of information. Supporters also point out that instead of eliminating diversity, viewers have had much more program options with th emergence of 24 hours news channels such as CNN and FOX News and specialized channels such as Discovery and History (Compaine, www.reason.com). In fact, Adam Thierer revealed that instead of the lack of diversity of programs, audiences are actually experiencing â€Å"information overload† due to explosion of media options. He pointed out that todays media environment is â€Å"diverse and characterized by information abundance† (Thierer, p.2). The issue, as FCC concluded in revising the Telecommunication Act, â€Å"was whether media companies will be able to dominate the distribution of news and information in any market, but whet her they will be able to be heard at all among the cacophony of voices vying for the attention of the Americans (FCC proceedings, p.149) 2) The three broadcast networks ABC, CBS and NBC did not face a broadcast network competitor until Fox emerged in the 1980s and the WB, UPN and Univision grew in the 1990s. Why did these networks emerge when they did? What regulatory changes aided their growth? How did they differ from the other networks in terms of their relationships with their affiliates? What audiences did they target and what types of programs did they use to do so? How did they change as they grew? You may choose one or more network(s) to illustrate your points. From the 1950s to the 1980s, the big three networks dominated the American airwaves. Independent and local television networks would occasionally penetrate the national airwaves but most of these did not survive due to financial constraints. It was in 1986 however that the first rival to the big three emerged with the establishment of   FOX Network.It started out dabbling in TV business by producing and distributing shows for the three big networks. In 1985, Rupert Murdoch bought 50% shares in the 20th Century Fox   movie and television studios. When Murdoch finally achieved full ownership of the studios, he proceeded to buy television stations owned by Metromedia which gave Murdoch a foothold in the major U.S. cities such as New York, Washington, Los Angeles, Dallas, Houston and Chicago (www.teletronic.co.uk). This move would spur Murdoch to create a â€Å"fourth network†. In a brilliant move, the new Fox network labeled their new venture as a â€Å"satellite-delivered programming service†(www.teletronic.co.uk). This enabled Murdoch, who was not a citizen, to bypass FCC rules such as foreign-ownership and the definition of FCC of a â€Å"network† as â€Å"airing more than 20 hours of programming per week†. These enabled Fox to operate unhindered by the FCC rules on networks, thus being able to still distribute its TV productions to other networks but only airing 2 hours of primetime shows as opposed to the 3 hours of the big Networks. When it was launched in October 1986, almost 96 stations were connected to Fox enabling it to reach 80% of American audiences. Before making it big, Fox had to start from scratch in expanding its audience share. The network first major release was the â€Å"Late Show† with Joan Rivers. They hoped to capture the 11:30pm late-night slot and targeting young audiences. This strategy however failed as ratings fell with viewers switching back to their previous stations. Despite these failures, Fox continued to lure the younger to middle -aged viewers with shows such as â€Å"Tracy Ulman† which won the station its first Emmy, â€Å"Marriedwith   Children† which would be its first biggest hit and â€Å"21 Jump Street† which was its first drama. These shows were some of the first forays of the network into the Sunday prime-time slot. Although they were received lukewarmly at first, these shows would gain momentum in the coming years. The success of Fox would lead to FCC relaxing the Fin-Syn rule and redefining their concept of â€Å"network†, which would finally result in the elim ination of the Fin-Syn Rule in 1995. (www.museum.tv) The success of its first primetime shows would lead to Fox introducing documentary-style shows such as â€Å"Americas Most Wanted† and â€Å"Cops†. But their biggest success would come in when Fox reintroduced animation to the primetime slot with â€Å"The Simpsons†. The animated show would penetrate the top 30 primetime ratings and would then become the longest running comedy show on television (www.teletronic.co.uk). Soon, Fox found its niche by veering away from conventional shows, like game shows and   talk shows, by introducing reality-based shows and shows that targeted the young viewers. Fox owner Rupert Murdoch would change the media landscape when it snatched exclusive rights to air the National Football League in 1993 (Kimmel, p.162). This move would cement Foxs role in the ratings game. As of today, Foxs main draw is its reality-based shows such as American Idol that have dominated airwaves since its release in 2002, capturing much of the 18-49 viewer demographic (tvbythenumbers.com). With success comes controversy. Such was the case of the Fox news network as critics accused it of being biased towards the U.S. Republican Party (Greenwald, p.4). Despite these, Fox shows and its affiliated cable channels still rake in much of the ratings with Fox News attracting 2.4 million viewers in the first quarter of 2009 (Gold, www.latimesblogs.latimes.com)

Five Functions Of Language (Leech, 1974)

Five Functions Of Language (Leech, 1974) Language plays a very important role in human lives. It is a social phenomenon. One of the main goals of language is to communicate with people and to understand them. When someone speaks, he intends a specific purpose. He wants to convey a message through that language. A person uses his language to many different purposes for example, to express his feelings, to ask for help and to apologize. In fact, we use language in many different ways, some of these are, the informational, the expressive, the directive, the phatic, the aesthetic. We use language and that language is a part of society. Actually, any language varies according to , the nature of the society, what kind of people, and their attitudes. People use language according to their situation. The social background of any person can play an important role in the kind of language he has. I am going to discuss these functions and take some examples of each one. I will explain the relationship between language and social organization. Language is very important factor of communication among society. Using language has some functions. We need to use language to fulfill our needs. It is a crucial part in our life. If a person uses his language, he chooses words that matches his needs. People use some functions to say a sentence, to ask, to reply, to greet and etc. In fact, forms are important part of our discussion because they are related to functions. A person who says, What is your name? he is showing a form of a question. Let us take another example, I want to play football, functions as a statement. Five functions of language: Actually, Geoffery Leech( 1974 ). Mentioned that language has five functions. They are: Informational   Expressive   Directive   Aesthetic Phatic I am going to discuss every function. Informational function which every one tends to assume is most important Geoffery Leech( 1974 ). In fact, this function concentrates on the message. It is used to give new information. It depends on truth and value. Let us look at this example, the car is big, the bus is crowded. language can have an expressive function: that is, it can be used to express its originators feelings and attitudes swear words and exclamations are the most obvious instance of this. Geoffery Leech( 1974 ). The speaker or writer of this function tries to express his feelings. He or she reflexes his or her impression. This function could give a clear image for the personality of the speaker or writer. The best example of this kind is Poetry and literature . In fact, this function evoke certain feelings and express feelings. Examples of this kind are, I am very happy or I spent a wonderful vacation. We can see from the previous examples that they reflex the feelings of the speaker or the writer. The third function of language is the directive function whereby we aim to influence the behavior or attitudes of others. The most straightforward instances of the directive function are commands and requests. This function of social control places emphasis on the receivers end, rather than the originators end of the message: but it resembles the expressive function in giving less importance, on the whole, to conceptual meaning than to other types of meaning, particularly affective and connotative meaning Geoffery Leech( 1974 ). Examples of this kind are, I want a cup of tea or close the door. It is clear hear that, we use the language in a direct way. We ask someone to do something. Some times we can use a sentence to express two functions. For example, I am thirsty. The previous example could be used to show the condition of the speaker or writer or to express the feeling. In a way that a person asks someone to give him water. The fourth function is the aesthetic function, which is the use of language for the sake of the linguistic artifact itself, and for no purpose. This aesthetic function can have at least as much to do with conceptual as with affective meaning Geoffery Leech( 1974 ). The function associated with the message-the vehicle-is the poetic or aesthetic function: the sign taken as an end in itself. All art understood as art is taken to embody this function, and any object valued for its beauty rather than for its ideological value or usefulness-whether a gorgeous car, an elegant teapot, or some acreage of untouched real estate-takes on this function. Although Jakobson, perhaps more precisely than anyone who preceded him, showed how the aesthetic function could hinge on structure, he argues that cultural norms ultimately determine the dominance of this function. As a striking demonstration, he notes that the aesthetic status that one generation accorded only to the poems of Karel MÃÆ' ¡cha , a subsequent generation accords only to his diaries. Jakobson, R. (1933). According to Leech, the fifth function is the phatic function. the function of keeping communication lines open, and keeping social relationships in good repair ( in Britain culture, talking about the weather is a well-known example of this). Geoffery Leech( 1974 ). We can say about this function that it is used for normal talks. An example of this, when two people meet each other accidently in a place. They start talking about something unimportant for the sake of communication like, how are you? How is your children? And so on. We can say that it is a kind of daily talking. It is not meaning but is good. Actually has another classification from what we have discussed. H. Douglas Brown has classified function of language into seven types. This classification is not much different from that of Leech. The functional approach to describing language is one that has its roots in the traditions of British linguists J,R Firth, who reviewed language as interactive and interpersonal, away of behaving and making others behave Berns, ( 1984).

Music in William Shakespeare’s Plays :: Biography Biographies Essays

Music in Shakespeare’s Plays    Elizabethans, during the time of the notorious William Shakespeare (1564-1616), were extremely sensitive to beauty and grace and had an undying enthusiasm for music and poetry. Music was a vital part of Elizabethan society; it was thought that a man who could not read music or understand it was poorly educated. The common entertainment and amusement was centered on music, song, and dance, people of all classes enjoyed the splendor of the music at this time. Since music was so popular and so widely understood, it is little wonder that most Elizabethan plays, including Shakespeare’s plays, have music in them.      Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Shakespeare uses music in his plays for several reasons, all of which are extremely significant. The first is evident in which music was so popular during this time that it influenced the performed plays. Shakespeare had a mixed audience who enjoyed and attended his plays. Music, which was understood practically universally allowed everyone to understand his plays and relate to them more easily. If people did not understand the language or the plot, the music could make it easier for them to follow along.      Secondly, on the stage music played a very important role. Music contributed to the atmosphere and set the mood in many of Shakespeare’s plays.   There was a special musicians’ gallery above the stage, the music sometimes was played on the stage, and there were occasions when it was played under the stage to achieve an eerie effect. During comedy plays gentle songs would be played with the lute and during tragedies and histories the sounds of trumpets and drums would echo through the theater. For example, if a king entered the trumpets would sound and everyone would know who it was. The Twelfth Night is also a good example; it includes instrumental serenades and rousing drinking songs, all to show the gaiety and sadness for the mood of the play.      Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Some songs and music are intended to represent a soliloquy, when private thoughts and feelings are performed. Songs, music, and sound effects represent themes, tones, moods, emotions, and even people. Shakespeare, being a lyric poet, used fifty or more songs in his plays and wrote hundreds of stage directions calling for music.

Peer Violence Essay

Peer violence/abuse is something that takes place in the everyday life of some people and their families. Peer violence/abuse is when a person undergoes improper or unfair physical or verbal maltreatment, injury, sexual assault, violation, unjust practices, wrongful practice or custom, offense, and crime. There are many different types of peer violence such as verbal, physical, cyber bullying, and social alienation. As you continue to read you will better understand the effect, consequences (in school and out of school), and examples of peer violence. Youth violence has played a big part of everyday life for some; youth violence includes bullying, punching, slapping, verbal abuse and using weapons, towards another. These violent acts are a disruption to people’s lively-hoods and to the learning process. The most serious effect that youth violence has on people is death and injury; most students are victims of homicides in the schools and suicides at home. Most of these deaths occur before, after, or during lunchtime. Other victims can be examples of nonfatal injuries like cuts, broken bones, bruises and even gunshot wounds. Some can even have a long-term effect on a person emotionally/mentally, a person can suffer depression, fear other people, anxiety and even post-traumatic stress which does not just effect the person but it also effects the persons immediate family and close friends. Peer violence can affect the way a child lives and their lives, they will feel shame for being a victim and won’t tell anybody what’s going on and could be afraid that the problem might escalate if they do tell a trusted adult. In recent news, in Southern Las Vegas two brothers were sentenced to jail and correctional facilities for the bullying of a disabled boy who attended their school. The boys had one of their friends record the attacking of the boy and posted it on YouTube. One of the boys was sentenced to 12 months of probation and 40 hours of community service while the other was sentenced to serve time at Spring Mountain Youth Camp with supervision until released. Consequences are one of the things many people do not think about before they began bullying each other or began attacking one another. In most schools a punishment is 3 to 6 days of suspension and even a court date with the victim. In Las Vegas depending on your age you can get anything from probation to 30 days in a juvenile correction center or a correctional center such as boy’s town or Spring Mountain Youth Camp. http://en.wikipedia.org/wiki/Columbine_High_School_massacre#Medication http://www.modernmom.com/article/the-effects-of-school-violence-on-victims http://www.modernmom.com/article/the-effects-of-school-violence-on-victims

Narrative and United States Respond Essay

Directions: Imagine yourself as one of the children in the liberation photograph. Complete the three paragraphs as a first-person narrative from his or her point of view. Paragraph 1: Why were you persecuted? Paragraph 2: Where did you go? Describe your experience at the camp. What happened to your family? How did the United States respond to your experience? Paragraph 3: What will your future bring? Predict what you think will happen to you now that you have been liberated. How has the world changed since your imprisonment? How have you changed? In your narrative, be sure to: recount historical facts accurately use course terms when appropriate cite any outside sources The Nazi’s came into power, and that’s when everything changed. Famailies were broken,homes were destroyed,and businesses were ruined. We were the targets for this burtla attack. The Jews. My name is Lauren and my family and I have been taken to a camp. We are in Amersfoort in the Netherlands. This camp is a transit and prison camp. I have been hearing it is less harsh then the other camps, such as extermination camps. We have been here since June 23, 1944. It is small, yet it contains about 35,000 prisoners. The Dutch Jews that resign here right now are slowly being sent away. My dad won’t tell me where, but I know it’s to extermination camps. It is very warm here, which makes sleep uncomfortable at night†¦not that we get much of it anyways. I am thankful I am still with my parents though, it is just us. The food here isn’t good either. Don’t supply enough. I can feel myself getting weak and it has only been one day†¦how much longer can I last? The Dutch Red Cross and Canadian Army is supposed to be sent here sometime soon. Oh, I hope it is soon. This is horrible. April,1945: The point of light has come. The Canadian Army has taken seige and is setting us free! Oh I am so thankful. Now that the war is ending, my family and I can only hope for more good to come. The future will be difficult, for I know it’ll be hard to get over the trauma and pain we have all experienced. Those who have survived will be forever scarred. The world is different now. Everything seems black and grey. Everyone is sad and gloom, yet they should be. Many people have been hurt and killed nd seperated. Not only the Jews, but the countries involved are hurting. I am a stronger person now. I hope to shine my strength upon others around me. I know that when I grow up I will make a difference in these people’s life and show them to not hold a grudge, though it may be hard, but to forgive so that they may life eternally forever.

Animals Have Rights Too essays

Animals Have Rights Too essays Have you ever had a missing dog or cat? They were probably a beloved member of your family. What could have happened to your loyal companion will shock you. Many states have laws that require local pounds to turn over those animals who have not been claimed with in five days of their arrival to laboratories. This practice is called pound seizure. The animals, which consist of cats, dogs, kittens, and puppies, are used in medical experiments. There is no federal law related to pound seizure, but there have been several anti-pound seizure bills put before Congress. None have been enacted. Animal advocates strongly object to the practice of pound seizure. An animal that may have once been a loving family member is forced to have its life ended in a laboratory. The Associated Press reported in December of 1995 that two-thirds of 1,004 Americans polled agree that an animals right to live free of suffering should be just as important as a persons right to live free of suffering. Americans should stand up for what they believe and make the world a better place for animals. A complete count of animals used in research is unknown because federal laws do not require research institutes to record the number of rats, mice, and cold blooded animals that are used in experimentation. Estimates for total numbers range from 20 million to 70 million. So why are so many defenseless animals killed? Many would say that there have been many medical breakthroughs thanks to animal experimentation, but the historical value of animal research with regard to humans remains questionable. Dr. Edward Kass of Harvard Medical School said, ...primary credit for the virtual eradication of these diseases must go to improvements in public health, sanitation, and the general improvement in the standard of living. Over 44 million Americans have inadequate healthcare. If we really want to improve human health, ...

the man essays

the man essays touch at the site of the shot. This is a normal reaction to the medicine. You have a high temperature. Pain in the wound gets worse and won't stop. You have signs of infection (redness, swelling, pus, a bad smell, or red streaks leading from the wound). You have numbness or swelling below the wound, or you cannot move the joint below the wound. deadly poison. Slade was known to evaporate alcohol from everyones barrels, so when he had the chance to steal some of Mr. Baumers, he did, dying a foolish death. There is no way Mr.Baumer should be blamed for this foolish act that Slade caused, due to him only wanting to clean his barrels with wood alcohol. If I was empty-headed as Slade and went around evaporating alcohol and died, I would be the one for the blame! If it wasnt for brainless people like Slade in the world today, we wouldnt be in this courtroom right now. In conclusion, it all comes down to the fact that Slade did it to himself by going into Mr. Baumers property and stealing his alcohol. It doesnt matter how many reasons there are that Mr. Baumer wanted to kill him, it wouldnt have even mattered if he gave him a death threat. Once again I say this again, it matters that Slade was the one that came into his property and drank the whiskey. Also there is no evidence that Mr. Baumer murdered this man of disgust.. So what can the plaintiff prove Now I rest my case. Im sure that my explanations have surely been enough to prove Mr. Baumers innocence. If he found guilty of a crime he did not commit, then an innocent man will be locked up behind bars for a long time. He would be sitting in his cell suffering and wondering what he did to deserve such pain. Then all of you jury would have guilt inside your souls haunting you in your sleep and day. Im sure ...

7 Eleven Target Market

7 Eleven Target Market This investigation of the small business, 7-Eleven chain store, was conducted over two month period from July, with many sources of information, such as the actual stores and the information from internet. The 7-Eleven chain store was established as an ice house in Dallas, Texas in 1927, and it is one of the world’s largest operator, franchisor and licensor of convenience stores. This article seeks to explore a comprehensive description and understanding about 7-Eleven and try to find out the secret of success, as well as giving some suggestions. The 7-eleven chain store was started out in 1927 and was introduced to Australia in 1977. An ice dock employee in the Southland Ice Company began to offer milk, bread and eggs on Sundays and evenings when grocery stores were closed. This new business idea produced satisfied customers and then the chain store was established. In November 2005, 7-Eleven, Inc. became an indirect subsidiary of Seven & I Holdings Company, a Japan-based or ganization. Their prime function is to consistently serve the changing needs of customers for their convenience. The store can always adapt quickly to meet the customer’s changing needs. It is the most obvious feature that makes it different from other convenience stores. With the newest products and services applying in the store, and the newest ways of business operation, the store can be operated more efficiently than others. For short, the perpetual improvement made the store keeping ahead in so many brands of chain stores. As a convenience store, 7-Eleven mainly faces three types of competitors. The first on is supermarkets, such as Wal-Mart. Second, small shops (probably not has a brand). Third, other brands of convenience stores, such as Lawson (founded in 1975 in Japan). The targeted customer is young single working people, usually un-married, as a result, the location of 7-Eleven always near office buildings, shopping malls, parking lots, subway station, et al. Besid es the traveler is also its main customer. In Australia, â€Å"stores in suburban areas often operate as petrol stations† (wikipedia.org, 2010). 7-eleven, Inc. is the word’s largest convenience retail chain. The company operates franchises and licenses more than 7,100 stores in the U.S. and 7-Eleven licensees and affiliates operate approximately 31,400 7-Eleven and other convenience stores in countries including Japan, Taiwan, Thailand, South Korea, China, Australia, et al (7-eleven.com, 2010). The main distribution of 7-eleven around the word can be seem in the table bellow fig.1 Fig.1 the main distribution of 7-Eleven around the word Territory First Store Opened Number of Locations United States 1968 584 Canada + 1969 457 Mexico 1971 1,180 Japan 1971 12,753 Australia 1977 397 Sweden 1978 191 Taiwan 1980 4,735 China (Hong Kong, Shenzhen, Guangzhou & Macau) 1981, 1992, 1996, and 2005, respectively 1,680 Singapore 1983 493 Philippines 1984 469 Malaysia 1984 1,115 Norway 1986 177 South Korea 1989 2,282 Thailand 1989 5,409 Denmark 1993 126 Beijing, PRC 2004 93 Shanghai, PRC 2009 20 Indonesia 2009 5 Rsource: http://corp.7-eleven.com/AboutUs/InternationalLicensing/tabid/115/Default.aspx (4) Suppliers It can be seen from the table bellow that the most commodity of 7-Eleven is food, in which the processed food account most. As a result, the main supplier of 7-Eleven is food maker, especially who produce the processed food. The non-food products suppliers is various, such the provider of a variety of prepaid card.

Summarize Research Paper Example | Topics and Well Written Essays - 500 words - 1

Summarize - Research Paper Example The service provided by the company is still unique but over the years it has received significant popularity in the cities in which the company operates. The car sharing service provided by the company is economically feasible and the rationale behind the service is also encouraged by the environmentalists and the users alike. According to a survey conducted in the year 2006, it was found out that one-third of the users of the company either sold out their vehicle or gave up the idea of acquiring their own vehicle. In this manner the company met its objective of reducing the number of car owners. One of the objectives of the company is to reduce the amount of pollution that results from harmful emissions from car use. By providing a vehicle to a subscriber for a limited period of time, the company succeeds in its objective of discouraging prolonged usage of cars. In this way harmful emissions can be reduced and the overall pollution in the environment can be slowed down. The company provides the car sharing service in the following manner. The subscriber is required to reserve a vehicle at a specified station of the company either in person or by making a call. The subscriber is also required to specify the time when the car would be needed.

Eating Habits of Students Essay Example | Topics and Well Written Essays - 1750 words

Eating Habits of Students - Essay Example The importance of a healthy lifestyle is inevitable. A good and healthy lifestyle starts with the diet one takes (Bailey, 2007 ). A blend of calorie intake together with fruit and vegetable consumption, as part of the diet, is advisable in ensuring a balanced diet. It helps prevent lifestyle-related disorders and diseases (MacClanccy, Henry, & Macbeth, 2009). Strict dietary guidelines help maintain a healthy diet and avoid the big gap in dietary divide experienced today by many people. The prevalent short lifespan emanates from the wrong choice of diet that end up affecting our health (Shepherd & Raats 2006). The young generation seems to pay little attention to the crucial topic of diet and health. Their choice of diet remains a secondary consideration in their responsibility for their health (Gullotta, Adams & Ramos 2005). Dietary disorders among young people are on the rise at an alarming rate. Instances of obesity in young people are increasing more than ever experienced. Accordi ng to Richards, 2007, guiding the young generation on issues of diet and health become essential. Topics such as the choice of food, awareness of a well balanced diet and the need to create attention to nutrition among by young people need further elaboration. Teaching the youth about diet and health, therefore, is indispensable an issue most governments must consider engaging (Berg 2002). Statistics in the United Kingdom show that several schools going students have poor knowledge of diet and health (McGinnis & Gootman 2006). Several students express low attention to nutrition. The choice of a better diet by students is poorly in several students (Glass 2009). In what areas many students pay less attention to, as far as diet and health are concerned, this report sorts to find out. The report discusses the important dietary areas overlooked by students and their extent of caution to their health. 2. Method In order to find out the eating habits of students, a survey was conducted wi th the help of an oral questionnaire. Total 30 randomly selected students in the UK took the interview in different learning institutions for the purpose of representing the student population. The group of respondents composed of students from different learning institutions at different stages of studies. The respondents consisted of fifteen boys and fifteen girls. The questionnaire (attached in the appendix) consists of different kinds of questions which chiefly build upon each other. The question types used is, for example, â€Å"yes/no†, multiple choice and ranking questions. In addition, some questions require the respondents stating their own opinion or telling more about their own experiences. While the questionnaire is not plainly segmented, it focuses on one major topic of health and diet. The questionnaire consists of seventeen (17) questions. The first question asks about the respondent’s gender. The second question asks about the frequency of meals taken b y students per day. The number of meals ranges from one (1) to four (4) per day. The third asks the opinion of the responder, whether he or she gets a balanced diet. It offers five options of response to the question. The fourth question inquires the respondent’s knowledge of a balanced diet. The fifth question asks the respondent about his or her preferred meal.

The Importance of Learning Discipline in School Essay

The Importance of Learning Discipline in School - Essay Example The Importance of Learning Discipline in School Learning is an important element is schools and basically involves the promotion of discipline I various form. The attitude that a child is given at a young age to a great extend influences the study patterns and especially at a young age. There are some who feel we stop being creative, or are sitting in a classroom learning the same thing we would be better off learning on our own in an unstructured setting. This is true to some extent, but in every job and every career there are tasks that are boring or hard to do. Many people will take jobs that are boring or hard, but the ones that will give them an income for their entire lives if they are willing to work for it. The education a student receives in school should be the basis for their willingness to get up every day and go to work and earn some living no matter how hard the job is. Students go to school so that they may gain some disciplines needed in their careers, they are also learning how they should maintain their jobs even if it is a hard one. The discipline to get and go to school and do the homework is the same discipline that is needed to get up and go to work every day. It is valuable to have discipline no matter what we are trying to complete. The schoo l gives us a way to learn discipline. It would be nice if the world were made up of jobs that only had parts that were fun to complete. For instance , if the jobs would be fun like watching video games, movies or spending time with friends everyone would like to complete his or hers. Unfortunately jobs have parts that are too boring, or ones that are difficult. There are ones that we just don`t like to do, but to get a degree we must complete the courses. So we force ourselves to go to the classes and do the homework. In the process we learn to discipline ourselves. There is a reward at the end, a diploma and the possibilities of the careers. What our education includes is the discipline we learned that apply to our career that will help us to succeed. Not everyone manages to get through public school, let alone college. Some students lose interest in school. Students that drop out of high school lose many opportunities to get a good paying job. They struggle to keep even low paying jobs that they have no interest in. What they have lacked is the discipline they would have learned if they could have completed their school course. In john Holts article `` school is bad for children’’, he talks about why students lose interest and give up, never learning why an education is good and missing out on the discipline that comes with it. `` If we don’t make you read, you won`t, and if you don’t do it exactly the way we tell you can't’’, John Halt. In short, he comes to feel that learning is a passive process, something that someone else does for you, instead of something you do for yourself (Holt 64. The point being that the school is the one that instills the entire discipline one need in his career and this is just done through learning. Holt goes on to explain in more how schools not only do not teach discipline, but in still other bad qualities in students. He refers to a student; `` He learns to be lazy†¦ how not to work’’ (Holt 65). Holt’s articles are trying to get the points across that given the right circumstances at school that a student would learn on their own. They would learn the discipline through their own curiosity about the world. Of course, it is the job of the school to teach discipline though parents have a lot of control whether the students learn discipline or not. They are the children first example of how to go about learning discipline. The parents should encourage their children to go to school. In Lynda’

Aspects of intercultural communication in international business Essay

Aspects of intercultural communication in international business - Essay Example At the same time it is not easy to engage in effective international communication because of the cultural, social, political, environmental, legal and communal differences between the countries. Verbal and nonverbal communication aspects are different between countries and the organization planning for internationalization must give proper training to their employees for effectively communicating with the people of the target country. In order to analyse the importance of intercultural communication in international business this paper evaluates probable intercultural communication strategies an American company needs to adopt in China, with the help of cultural dimensions of international communications formulated by Hall, Hofstede, Trompenaars and David A Victor It is possible to communicate using the mother tongue. But, even using mother tongue, it is difficult to communicate effectively. Communication is a complex process which is associated with so many parameters. Communication occur both in verbal and nonverbal forms. In fact most of the communication occurs in nonverbal format compared to the verbal format. Body language, gestures, facial expressions etc can communicate lot of things. Fox (2004), has pointed out that even the dresses can communicate so many things about a person or culture (Fox, 2004, p.275) Cross cultural communication is an existential necessity (Wierzbicka, 1997, p.21). Especially in the current globalized era intercultural communication is necessary for international business and cultural integration. Intercultural communication is the most difficult one because such communication can lead towards misunderstanding if not controlled properly. Berger (1996) has mentioned that intercultural communication continually involves misunderstanding, misperception and misevaluation (Berger, 1996, p.72). Desire to understand and connect with the host population, self knowledge, self assurance and control,

Compare the Boston with PA and answer the following questions Essay

Compare the Boston with PA and answer the following questions - Essay Example Thus, the Greater Boston region is a home to 4.5 Million people. The city’s population density is 5,203 people per square mile. On the other hand, basing on the 2010 United States Census, Pennsylvania has a population of is 12,742,886 people (Sapp and Solomon 81-82). With respect to land composition, Palo Alto has a total area of 25.8 square miles.1.9 square miles is covered by water while 23.9 square miles is covered by land. On the other hand Pennsylvania covers a total of 46,055 square miles of which 1239 is covered by water whereas 44,817 square miles is covered by land. In terms of average income, as determined by the 2000 U.S Census statistics, the average income for the Bolton city is $39,629. The average family income is $44,151. The per capita income of the city is $23,353. In addition, 19.5 percent of the population as well as 15.3 percent of families live below poverty line. On the other hand, Pennsylvania has a Gross State Product of $570. It has an average per-capita GSP of $39,830.In terms of poverty, 4.8 percent of the population and 3.2 percent of families live below poverty line (Sapp and Solomon 84). With regards to lifestyle, Boston has one of the highest living cots in the United States. It is an international hub for reputable higher educational and medicinal centers. The city has been ranked third in the United States as per livability rankings. On the other hand, the people in Pennsylvania like mushroom and wine. The quality of life in the state is incredible as well. It is also a religious center with the notable churches being the Roman Catholic and protestant churches. The two cities have taken various initiatives in enhancing a reduction in environmental pollution and promoting environmental conservation. In this purview, it is apparent that Boston has always been in the frontline to ensure environmental conservation. This is bolstered by the Boston

The Importance of Learning Discipline in School Essay

The Importance of Learning Discipline in School - Essay Example The Importance of Learning Discipline in School Learning is an important element is schools and basically involves the promotion of discipline I various form. The attitude that a child is given at a young age to a great extend influences the study patterns and especially at a young age. There are some who feel we stop being creative, or are sitting in a classroom learning the same thing we would be better off learning on our own in an unstructured setting. This is true to some extent, but in every job and every career there are tasks that are boring or hard to do. Many people will take jobs that are boring or hard, but the ones that will give them an income for their entire lives if they are willing to work for it. The education a student receives in school should be the basis for their willingness to get up every day and go to work and earn some living no matter how hard the job is. Students go to school so that they may gain some disciplines needed in their careers, they are also learning how they should maintain their jobs even if it is a hard one. The discipline to get and go to school and do the homework is the same discipline that is needed to get up and go to work every day. It is valuable to have discipline no matter what we are trying to complete. The schoo l gives us a way to learn discipline. It would be nice if the world were made up of jobs that only had parts that were fun to complete. For instance , if the jobs would be fun like watching video games, movies or spending time with friends everyone would like to complete his or hers. Unfortunately jobs have parts that are too boring, or ones that are difficult. There are ones that we just don`t like to do, but to get a degree we must complete the courses. So we force ourselves to go to the classes and do the homework. In the process we learn to discipline ourselves. There is a reward at the end, a diploma and the possibilities of the careers. What our education includes is the discipline we learned that apply to our career that will help us to succeed. Not everyone manages to get through public school, let alone college. Some students lose interest in school. Students that drop out of high school lose many opportunities to get a good paying job. They struggle to keep even low paying jobs that they have no interest in. What they have lacked is the discipline they would have learned if they could have completed their school course. In john Holts article `` school is bad for children’’, he talks about why students lose interest and give up, never learning why an education is good and missing out on the discipline that comes with it. `` If we don’t make you read, you won`t, and if you don’t do it exactly the way we tell you can't’’, John Halt. In short, he comes to feel that learning is a passive process, something that someone else does for you, instead of something you do for yourself (Holt 64. The point being that the school is the one that instills the entire discipline one need in his career and this is just done through learning. Holt goes on to explain in more how schools not only do not teach discipline, but in still other bad qualities in students. He refers to a student; `` He learns to be lazy†¦ how not to work’’ (Holt 65). Holt’s articles are trying to get the points across that given the right circumstances at school that a student would learn on their own. They would learn the discipline through their own curiosity about the world. Of course, it is the job of the school to teach discipline though parents have a lot of control whether the students learn discipline or not. They are the children first example of how to go about learning discipline. The parents should encourage their children to go to school. In Lynda’

Compare the Boston with PA and answer the following questions Essay

Compare the Boston with PA and answer the following questions - Essay Example Thus, the Greater Boston region is a home to 4.5 Million people. The city’s population density is 5,203 people per square mile. On the other hand, basing on the 2010 United States Census, Pennsylvania has a population of is 12,742,886 people (Sapp and Solomon 81-82). With respect to land composition, Palo Alto has a total area of 25.8 square miles.1.9 square miles is covered by water while 23.9 square miles is covered by land. On the other hand Pennsylvania covers a total of 46,055 square miles of which 1239 is covered by water whereas 44,817 square miles is covered by land. In terms of average income, as determined by the 2000 U.S Census statistics, the average income for the Bolton city is $39,629. The average family income is $44,151. The per capita income of the city is $23,353. In addition, 19.5 percent of the population as well as 15.3 percent of families live below poverty line. On the other hand, Pennsylvania has a Gross State Product of $570. It has an average per-capita GSP of $39,830.In terms of poverty, 4.8 percent of the population and 3.2 percent of families live below poverty line (Sapp and Solomon 84). With regards to lifestyle, Boston has one of the highest living cots in the United States. It is an international hub for reputable higher educational and medicinal centers. The city has been ranked third in the United States as per livability rankings. On the other hand, the people in Pennsylvania like mushroom and wine. The quality of life in the state is incredible as well. It is also a religious center with the notable churches being the Roman Catholic and protestant churches. The two cities have taken various initiatives in enhancing a reduction in environmental pollution and promoting environmental conservation. In this purview, it is apparent that Boston has always been in the frontline to ensure environmental conservation. This is bolstered by the Boston

The implications of the European monetary union Essay Example for Free

The implications of the European monetary union Essay In this report, I will be addressing the implications of the European monetary union and the problems Zeus will have in developing their market in Europe. The UK and EMU When the UK decided not to join the European monetary union (EMU) in 1999, it affected UK businesses, especially those who trade within the EU. Does it matter whether sterling is in or out? For many UK Businesses, trading within the EU has become more competitive. After the introduction of the Euro, an Italian company for example, competing for a German companies business could cut 3% of costs due to their common currency, making it harder for UK business to compete. Currently UK businesses are paying à ¯Ã‚ ¿Ã‚ ½3bn per year in exchange rates, which hit small firms like Zeus the hardest. Advantages By joining the single currency, British businesses will benefit from a fixed exchange rate allowing businesses to plan and budget for future activities more accurately. Fixed exchange rates will deliver stability and increase confidence that will lead to more investment and jobs. By staying out of the Euro Britain will be at a disadvantage to competitors in the Eurozone who already trade with each other using the same currency. The development of free trade has contributed enormously to the economic prosperity across the EU, with the strong position of the wealthier nations and helping to bring the poorer nations more stability and economic success. The introduction of a single currency removes one of the final barriers to free trade i.e. the transaction costs and the uncertainty involved in currency conversion. The removal of national currencies will encourage cross-border investment since the traditional reluctance of many investors to move their money into a currency other than their own will no longer be a factor. Businesses across the Eurozone will therefore be able to attract more investors from other Eurozone countries, and investment will be based on the competitiveness of a business rather than its nationality. This will increase the pressure on uncompetitive businesses to improve their efficiency. An increase in cross-border mergers and acquisitions will also lead to more streamlined and efficient businesses across the Eurozone. Disadvantages Most of Britain international trade is carried out in US dollars, a currency against which the pound has enjoyed far more stability than has the Euro. The fact that the pound has risen so much against the Euro since the Euros launch is a sign of the Euros weakness. Changeover to the Euro would be endured by all businesses in the UK, whether or not they trade with Eurozone countries. Most British companies, sell to local markets. These firms would still incur the costs of conversion and not see any benefit from the removal of currency transaction costs. While there would be a saving from the absence of currency transactions for exporters, these would be offset by the costs of the changeover. There have been fears that inward investment in British based industry would suffer as a result of staying out of the Euro, the reality has been very different. In 2001 the Office of National Statistics reported that inward investment in Britain for the 2000/2001 financial year was à ¯Ã‚ ¿Ã‚ ½341 billion, an increase of 36% over the previous year. The theory that a single currency will lead to the harmonisation and lowering of prices across Europe seems hard to support. Regional differences in prices are a result of differences in levels of taxation as well as variations in labour, property and transportation costs. The cost of living in different parts of the UK varies considerably, even though all regions share the same currency. Less scrupulous retailers would use the introduction of the Euro to round-up prices, just as they did during decimalization 30 years ago. How This Effects Zeus Being part of the EMU will benefit a small company like Zeus, (see advantages above) however, there are some other factors that Zeus need to be aware of. Promotion and packaging will also have to change. The language and content on the wrapping and will have to that of the country it is being sold in. Health and safety requirements of products would have to meet one standard rather then having to adapt products for different countries, however since Zeus currently trade mainly in the USA they would need to adapt their product to EU standards in order to trade within the community, which might be costly but beneficial. Cost of the Benefit If the UK were to join the EMU, cost increases and reductions will occur. Change of Equipment The costs for UK businesses of abolishing the pound and substituting the euro would be massive notes and coins would need to be replaced, along with cash registers, cash dispensing machines, accounting systems etc. The retail sector would have to undergo a complete renovation of cash systems. The costs of this changeover would affect all businesses in the UK, whether or not they trade with Europe and whether or not they will benefit. Consumers and businesses would have to pay for these costs through higher prices and taxes. It would take years before the trivial day-to-day savings on European transactions outweighed the costs of the changeover. More Competitive Markets The Euro ensures companies will face a more integrated European market. Cross-border trade and investment will be stimulated and competition strengthened in many markets. Businesses who see foreign exchange risk and transaction costs as barriers to cross-border trade are likely to move into new markets once these barriers are removed. New business start-ups may also be encouraged. Transparent Price Differences It will be possible to directly compare prices for the same goods and services in different EU countries and spot the best prices. Despite the SEM, price disparities persist as a result of differential pricing policies, tax rates, transportation costs, national market structures, and perceived product values. The ability for consumers to compare prices will move prices towards the lowest market level and businesses will find it hard to maintain pricing policies by country and currency. Treasury and Finance For many European businesses the Euro will present opportunities for long-term savings altering balance sheets, cash flow management, currency management, and corporate finance. Businesses with units operating in different currencies will be able to record and compare all accounting values, margins, costs, expenditures etc. in one currency. Such transparency may greatly assist in processes of internal planning, accounting, and benchmarking. Foreign Exchange Eurozone firms avoid the risk of exchange rate changes. Exchange rate movements dont impose a penalty but volatility in exchange markets and the unpredictability of rates can be costly. Many firms have opted to hedge exchange risks for long-dated transactions or included a margin in their prices to cover exchange rate movements. Under the single-currency, foreign exchange transaction costs are eliminated on internal dealings with benefits as much as 8% on the total price of industrial goods. Wage Transparency Employees will find it easier to calculate and compare wages between workers in different countries within the same company. Transparency of wages will bring salary convergence closer to reality and increase labour mobility. Variations in salary and remuneration exist today and workers always ask why are they paid that much over there when Im paid this much here?, firms can usually demonstrate difference in taxation, benefits, purchasing power etc. by country and currency. Organisations need to consider how to set fair and competitive remuneration packages in a Euro-denominated environment. Lower Borrowing Costs Its axiomatic with a single currency and single central bank that there will be a single interest rate. Banks will lend in Euros and enterprises will be able to borrow from outside their countries without incurring the risk of exchange rates, reducing borrowings costs. Cost savings may be greatest in countries where Euro interest rates fall below previous rates. The introduction of the Euro should favour the development of new financing methods. Overall, firms should have more choice and flexibility in raising finance and, in many cases, will face lower costs. How This Effects Zeus All these costs are going to affect Zeus and it might be a good idea for Zeus to look into these costs now, if they want to stay trading in years to come. Moving Production Many multi-national companies have expressed misgivings of Britain staying out of the Euro and state it could affect investments in British jobs. Companies want to know the value of the goods they sell from the UK will not decrease due to fluctuations in the exchange rate between Britain and the European countries and the cost of British labour will not rise significantly due to a strengthening pound. However, American, Asian and other foreign companies favour the UK as a base for their European operations because of factors such as culture, language, a de-regulated, business friendly environment, and low levels of taxation and corruption. EMU entry could reduce the cost of capital for UK firms if long-term interest rates fell within the EU and if membership of a larger financial market reduced the cost of finance. These costs could fall for SMEs in particular if joining EMU lowers the barriers which prevent SMEs accessing EU financial markets and lowers the cost of bank lending. Over time, EMU is likely to boost cross-border investment flows and foreign direct investment (FDI) in the Eurozone. The UKs share of total EU FDI flows has fallen, coinciding with the start of EMU, and a corresponding increase in the share of the Eurozone. But against the backdrop of many other influences on FDI flows, its difficult to say EMU has boosted FDI within the Eurozone. Successfully operating EMU and UK membership of it on the right basis, would boost FDI over the longer-term. The longer membership of the euro is delayed, gains of increased inward investment are postponed. If sustainable and durable convergence is achieved, then the quantity and quality of investment would increase. How This Effects Zeus If Zeus was to relocate to Europe, there would be decreased production, transport and currency costs however the initial outlay moving into Europe will be costly but allow Zeus to be in the market they wish to operate in. The skills and expertise of the workforce of that county may not have what Zeus require and may cost more money training employees to the standard required. Moving production into a different country may benefit the company as all countries have differing resources, like labour. Zeus will need to evaluate all the factors involved in moving production and decided wheather it would be beneficial for them. Expansion in Europe With more than half the UKs trade with the EU and increasing integration of product, labour and capital markets, the UKs economic interest is best pursued through a deepening cooperation with other European countries as part of the Governments commitment to a strong EU and a successful EMU. As the Prime Minister said in November 2002: We should have more self-confidence because we are a leading European power, always have been and always will be. However, there are implications to expanding a businesses share in the European market. The Governments objectives These global and European trends are mirrored in the Governments central economic objective for the UK to build a stronger, more enterprising economy and a fairer society, extending economic opportunity and supporting those most in need to ensure that rising national prosperity is shared by all. and strategy Stability, productivity and employment opportunity are the foundations of the Governments economic strategy. Since 1997, the Government has taken tough decisions and introduced wide-ranging reforms to establish a platform of economic stability and to promote work and enterprise, tackle poverty and deliver sustained investment to modernise public services. The Governments decision on UK membership of the single currency must contribute to these objectives. The benefits from adoption to the euro depend on trade integration between the UK and the Eurozone through the elimination of currency fluctuations and transaction costs. The UK has increased trade within the EU since joining. Chart 5.3 shows how UK trade with the EU has risen by 5%. The impact of EMU on UK trade, competition, productivity and growth thorugh substantial possible gains EMU membership could enhance productivity in the medium-term by increasing trade and investment and stimulating competition, also helping to promote economic reform in the EU and encourage specialisation in the longer-term. Therefore, EMU could effect the five key drivers of productivity. Based on broad-based evidence on the impact of trade, it seems reasonable to assume that each 1% increase of trade to GDP increases real GDP per head by at least 1/3 % in the long run and perhaps as much as 2/3 %. In a best case scenario, with stability through sustainable and durable convergence, a long-term increase in trade with the Eurozone at the top of the 5% to 50% range and increased investment spurring competition, UK output could be around 9% higher over 30 years within a successful EMU than outside. This could add around 1/4% a year to GDP growth. but not without sustainable and durable convergence Conditional on the achievement of sustainable and durable convergence between the UK and the euro area. Where it is not assured, the trade benefits from EMU would be likely to be at the lower end of the range, meaning gains to trade and competition from membership could be negligible. Estimates suggest a lack of flexibility and convergence in some EU countries. However, EMU has increased trade within the EU by 3% and 20% since 1999. Volatility and uncertainty resulting from EMU membership in the absence of sustainable and durable convergence could have a negative impact on the actual level of UK output in the long-term. The Governments strategy to tackle the barriers to productivity growth and close the productivity gap, involves continued microeconomic reforms in the UK to target the five key drivers of productivity combined with support at the European level for policies to strengthen competition and the Single Market. How This Effects Zeus Expanding into the European market place has two major implications that Zeus will need to consider. Firstly that since EMU, theres increased competitiveness within the EU and Zeus may find it hard to compete if their strategy and overall business is not strong. And when the 10 new countries enter the EU and join the EMU, it could decrease sales and profits even production as their economies are weaker then the rest of the EU and would affect Zeus expansion into Europe. Political Implications There are as expected, political implications to expansion into the European marketplace. In the UK, taxation on businesses is not as high as other EU countries, as the UK government want to promote economic growth. If the EU were to set the level of interest and taxation for all Eurozone countries it may not be beneficial for all countries or their goals. It could be seen as too much involvement and lack of sovereignty power and could cause bureaucracy and federalism. It could be argued that by joining the EMU the UK would lose its economic and political sovereignty; something the UK is not currently ready to give up for the euro and its benefits. To protect their own interests, countries can restrict imports by putting limitations, subsidies, quota or import duties to imports to protect industries. But this does nothing to protract free trade within the EU. Free trade was developed to increase political and economic stability within the EU. How This Effects Zeus Businesses like Zeus will need to consider political implications. Zeus will benefit from the movement of free trade within the EU, and the low taxation within the UK for businesses, however there are other political issues that Zeus will need to consider whether they stay in the UK or move into Europe. These are; o Social policies ~ health and safety standards, holiday/sick pay, working time directive, working conditions etc. o Environmental requirements ~ such as noise and pollution levels, safety fittings etc. o Technological ~ does the technology meet business requirements? do the workforce know how to use the equipment? etc. Recommendation I would recommend that Zeus stay in the UK. When the 10 new countries join the EU, EMU will be affected and it would be well advised to consider in the future expanding into Poland as they are in the centre of the EU and have a highly skilled and are inexpensive workforce to employ. Currently it would beneficial for Zeus to stay in the UK due to the governments objective to build a stronger economy. I would recommend that Zeus seriously look into moving or expansion into Europe and see how this mirrors with current and demand. Bibliography Books Palmer A, The Business Environment, 2002 Mercado S, European Business, Pitman, 2001 Piggott J, International Business Economics, 1999 Davison Purple, The European Competitive Environment, 1995 Websites www.bbc.co.uk/bitesize/business www.gov.org.uk www.offical-documents.co.uk HND UNIT 29: European Business

Cellular Molecular Mechanisms Of Hutchinson Gilford Progeria Syndrome Biology Essay

Cellular Molecular Mechanisms Of Hutchinson Gilford Progeria Syndrome Biology Essay Hutchinson-Gilford Progeria Syndrome (HGPS or progeria) is a very rare autosomal dominant disorder which results in premature aging and eventually death. Patients are often very underweight at birth and will display conclusive symptoms of premature aging within 18-24 months, such as reduced body fat, hair loss and aged skin, alongside tissue and organ degeneration. Average lifespan for sufferers of HGPS is thirteen years and cause of death is invariably due to heart failure. Due to the nature of these symptoms, HGPS is referred to as an accelerated aging disorder. Currently, only 100 cases of HGPS have been formally documented, around 50 of which are children who are alive today; however it is estimated that a further 150 children worldwide currently suffer from HGPS, but have not yet been formally diagnosed. The identification of the HGPS mutation has only recently been identified and located on codon 608 of the LMNA gene, which codes for four types of lamin proteins: lamin A, lamin C, lamin Aà ¢Ã‹â€ Ã¢â‚¬  10 and lamin Cà ¢Ã‹â€ Ã¢â‚¬  2. These, along with the B-type lamin are responsible for keeping the structure of the nucleus together by forming a scaffold which lines and interacts with the nuclear membrane. The LMNA mutation leads to the expression of progerin, rather than lamin A, altering the structure of the nuclear membrane and leading to loss of nuclear integrity, DNA damage and a compromised DNA double-strand-break repair mechanism. This causes a variety of problems relating to normal cellular function as well as resulting in increased apoptosis and significantly decreased proliferation rates. Until recently, medical assistance for children with HGPS only involved treating the symptoms which accompany the disease, rather than the effects of the HGPS mutation; however in August 2009, clinical trials began testing the effects of farnesyltransferase inhibitors (FTIs) on HGPS patients. This was following experimental evidence from Toth et al (2005) who showed that human fibroblast cells expressing progerin had reversed nuclear alterations when treated with farnesyltransferase inhibitors in vitro. Introduction Aging is a normal and natural physiological process which all living things must experience, unless death should occur prematurely. Aging impairs verve and mobility, causes hair loss, weakens bones and inevitably will ultimately lead to death. As humans, the price that must be paid for our unique self-awareness is the knowledge that we will eventually age and die, forcing us to come to terms with our own mortality and compelling us to value youth. Patients suffering from HGPS are not given the opportunity to experience their youth in the same way as most. By 18-24 months their bodies are already showing signs of physiological aging and by 5 years old they will show more signs of age-related disease than many adults in their 70s. In young, healthy humans, cells are able to cope with the assault of DNA damage which all livings organisms will unavoidably encounter over time. Over time, the ability to deal with this damage lessens and the physiological process of aging will gradually occ ur. HGPS cells are not capable of dealing with this DNA damage to the same extent and so aging happens quickly and prematurely. Despite this, intelligence and cognitive function in children with HGPS are often above average compared to other children within their age bracket (Progeria Research Foundation, 2006). To understand the cellular and molecular mechanisms of HGPS, it is first important to understand the process of normal aging in healthy humans. Normal Physiological aging Aging on an evolutionary level may be described as a progressive decline in fitness (the ability to survive and reproduce) due to a decline in tissue functionality with increasing age (Partridge Gems, 2002). On a cellular level it may be described as a progressive functional decline and increase in cell mortality (Lombard et al., 2005). Although many theories have been proposed, no conclusive theory has been agreed upon to explain how or why we age. Aging is thought to be caused by various genetic and environmental factors. At the cellular level this progressive malfunction of tissue is thought to be due to accumulation of damage by various biomolecules which leads to cell loss or damage (Vijg, 2000). Usually the body has the ability to regenerate these damaged or lost cells through pools of stem cells, however the body does not have the ability to regenerate infinitely and over time this causes a decline in tissue functions typical of aging. This is consistent with the disposable soma theory of aging (Kirkwood Holliday, 1979), which states that cell repair and maintenance (including DNA repair, defence against oxidants, etc) are costly activities. To work to extend life indefinitely would make little sense, as in the wild many organisms have an extremely high mortality rate. Therefore, animals have evolved in such a way that energy invested in maintaining the soma is limited, so that the animal is kept alive long enough for it to reproduce, but not to keep it alive indefinitely. Past this point, the bodys regeneration mechanisms fail and physiological aging becomes apparent. From an evolutionary point of view, this theory makes more sense than others which are based around aging being a genetically inbuilt process, as this would provide no benefit whatsoever to the individual animal or the species as a whole. Aging may involve damage to a variety of cellular components; however damage to various DNA and RNA molecules is likely to be a major contributing factor. Despite the cells inbuilt mechanisms designed to repair damage, damaged DNA which has not been restored perfectly can lead to mutations with detrimental consequences. Balaban et al. (2005) outlines the potential role for damaged mitochondria DNA in the process of aging, however nuclear DNA is a more likely culprit. Mitochrondial DNA has thousands of copies present within the cell which can be replaced if damaged, whereas there are only two copies of nuclear DNA. Several studies have shown that as age increases, so does the risk of mutation (Martin et al., 1996) and there is substantial evidence to suggest a causal link between damage to nuclear DNA and physiological aging. Sedelnikova et al. (2008) showed that the level of double strand breaks (DSBs) that take place increase with age and older cells are less able to repair these DS Bs. Finally, there is the observation that symptoms of progeria are caused by defined mutations in DNA maintenance proteins, which leads to impaired DNA repair mechanisms (Musich Zou, 2009). HGPS belongs to a group of disorders known as segmental progeroid syndromes, characterised by early manifestation of features usually associated with normal physiological aging. They are consequently referred to as accelerated aging disorders. HGPS Background HGPS was first described over 120 years ago by Hutchinson (1886) and again later by Gilford (1904). Since its original classification in 1886, just over 100 cases of the disease have been documented. It affects around 1 in 4-8 million newborns all over the world with no preference for gender. Figure 1 Locations of children around the world who have been diagnosed with HGPG. There are currently 50 living children diagnosed with HGPS, most of whom reside in affluent Western countries. It is estimated that a further 150 children worldwide suffer from progeria but have not yet been identified due to insufficient means to diagnose in less prosperous countries as well as the rarity and complexity of the disease and the fact that the HGPS gene has only recently been identified. (Adapted from the Progeria Research Foundation, 2006) Children with progeria are often born appearing healthy, however shortly after birth it becomes apparent that weight and height gain are below that of which is expected of healthy children (Merideth et al., 2008). By 18-24 months of age they begin to display signs of premature aging, which can be seen in figure 2 below. Figure 2: A 3 and a half year old boy with HGPS showing typical progeroid symptoms. These include stunted growth, loss of hair and body fat, aged skin and unusually prominent eyes. Non-visible symptoms include stiff joints, atherosclerosis., osteoporosis and fatigue. Impaired growth does not seem to be due to any hormone inbalance/resistance or malnutrition. Cardiovascular problems are generally thought to be caused by loss of smooth muscle cells, disruption of the extracellular matrix and other irregularities in vascular structure. Life span ranges from 8 21 years with the average being around 13 years old. Death is almost invariably caused by atherosclerosis (Progeria Research Foundation, 2006). HGPS has recently been acknowledged as part of a family of diseases known as laminopathies, as it is caused by a dominant mutation on the LMNA gene. Before the identification of the gene responsible for progeria, diagnosis was carried out solely on the symptoms that have been mentioned. Thanks to the recent discovery of the mutated gene (Eriksson et al., 2003), diagnosis can be carried out based on the appearance of this mutation. HGSP is caused by a de novo mutation on the LMNA gene, although other progeroid syndromes may be hereditary. The lamins The LMNA gene codes for the nuclear A-type lamin proteins: lamin A, lamin C, lamin Aà ¢Ã‹â€ Ã¢â‚¬  10 and lamin Cà ¢Ã‹â€ Ã¢â‚¬  2 (Fisher et al., 1986). These, along with the B-type lamins are responsible for keeping the structure of the nucleus together by forming a scaffold which lines and interacts with the nuclear membrane. The structure of the nuclear lamina within the nuclear envelope is shown in figure 3. Figure 3: Structure and function of the nuclear lamina The lamina exists on the inner nuclear membrane (INM), providing structural support and helping with chromatin organisation as well as binding nuclear pore complexes (NPCs), nuclear proteins (purple) and transcription factors (pink). Barrier to auto integration factor (BAF) is a chromatin-associated protein which binds to the lamina and various nuclear envelope proteins (Coutinho et al. 2009) Fawcett (1966) deduced that the lamins are components of the nuclear lamina, a layer found between the chromatin and the nuclear envelope initially thought to provide structural support for the nuclear membrane and a location for the chromatin to attach. Recently, further roles of nuclear lamins have been proposed, including DNA synthesis, transcription, apoptosis and assembly of the nuclear envelope. It has been determined that several isoforms of lamins are encoded by three different genes: The LMNA gene encodes lamin A, lamin C, lamin Aà ¢Ã‹â€ Ã¢â‚¬  10 and lamin Cà ¢Ã‹â€ Ã¢â‚¬  2 and the LMNB1 gene encodes lamin B1 and LMNB2 encodes B2 and B3 lamins (Stuurman et al., 1998). Whilst every vertebrate cell expresses at least one type of B lamin, lamins encoded by the LMNA gene are only expressed in differentiated tissue. This observations suggest that lamin encoded by LMNA may have specific roles within certain cells. It is possible that the role of these lamins is in fact to induce or maintain differentiation within these cells, although no conclusive evidence has been presented to support this. It is likely, however, that A type lamins have roles related to and dependant on correct chromatin organisation and nuclear structure. This includes reformation of the nuclear envelope post-mitosis, transcription, DNA replication and nuclear positioning (Holaska et al., 2003; Spann., 20 02; Moir et al., 2000; Haque et al., 2006). Although studies have shown that LMNA deficient mice develop normally, shortly after birth growth problems occur (Sullivan et al., 1999). Shortly before cell division in the late prophase stage of the cell cycle, the phosphorylation of lamin subunits takes place, causing the nuclear envelope to break down. A-type lamins are the first to be disassembled, occurring during early prophase, whilst B-type lamins are disassembled during prometaphase (Georgatos et al., 1997). This course of action is thought to be a necessary requirement for the reassembly of the nuclear envelope after cell division have taken place (Burke and Gerace, 1986). However, studies such as those by Newport et al. (1990) have provided evidence against these theories, stating that when these disassembled lamin subunits are imported, they are done so into a formed nuclear envelope with fully functional pores. Perhaps is it possible that a finite number of lamin monomers are used in the reassembly of the nuclear envelope and the rest are transported in at a later stage. The role of lamins in DNA replication is unclear, however several studies have suggested that Xenopus interphase extracts were depleted of Lamin B3 which resulted in a lack of DNA replication (Newport et al., 1990), however it remained unclear whether this was entirely due to the absence of lamins or if other factors, such as a smaller and more fragile nuclear envelope, contributed. A later study by Moir et al. (2000) provided evidence to suggest that normal nuclear lamin organisation is required for DNA synthesis and that this dependency is completely unrelated to the insufficient formation of the nuclear envelope. It appears that when nuclear lamin organisation is incorrect, the elongation phase of replication fails to take place, probably due to an alteration in distribution of elongation factors, Replication Factor Complex and Proliferating Cell Nuclear Antigen. The potential role of nuclear lamins in transcription has been put forward by Spann et al. (2002), who disrupted the normal nuclear organisation of nuclear lamins using a dominant negative mutant lamin lacking the NH2- domain. This resulted in the inhibition of RNA polymerase II activity in both mammalian and embryonic Xenopus cells. Notably, RNA polymerases I and III were not affected. The role of lamins in apoptosis is directly related to the state of the nuclear envelope. Apoptosis is a very precise physiological mechanism for effective destruction of unwanted cells without causing inflammation or distress to other cells, as would occur in necrosis. Lamin degradation is one of the processes that occur during apoptosis, however several studies have suggested nuclear lamins play a role in the induction of apoptosis (Rao et al, 1996; Di Matola et al., 2001). Post mitosis, protein phosphatise 1 (PP1) is dispatched to the nuclear envelope to initiate lamin B reformation. If this process is abolished, lamin B is degraded and apoptotic signals take place. As previously mentioned, expression of lamins A/C is limited to differentiated cells. Due to their role in DNA replication and transcription, several researchers have hypothesised that they play a role in gene expression as well. Gupta and Saumyaa (2008) propose that specialised A/C lamin expression regulates gene expr ession in such a way which may prevent cell division and cause the cell to undergo terminal differentiation a form of programmed cell death. Lamins are also used for chromatin organisation and positioning within the nucleus, so cells with LMNA mutations exhibit a range of problems involving abnormal chromosome organisation. Glass et al (1993) showed that A lamins interact with chromatin by binding histones as well as indirectly through lamin-binding proteins such as LAP2ÃŽÂ ± and barrier-ro-autointegration (BAF) (Holaska et al., 2003). Cellular and molecular mechanisms of HGPS The most commonly reported mutation responsible for causing HGPS is LMNA  codon 608 in exon 11 (c. 1824 C>T). Although the LMNA gene encodes both A and C type lamins, only A lamins are affected as exon 11 is not present in lamin Cs. Whilst this point substitution does not result in an amino acid change (G608G ) it partially activates a cryptic splice site, resulting in the deletion of ~50 amino acids near the carboxyl terminal in lamin A (LAà ¢Ã‹â€ Ã¢â‚¬  50) but maintaining the CAAX site. Amongst the deleted amino acids is the ZMPSTE24 cleavage site, which is necessary for the maturation of lamin A. This results in farnesylation and carboxymethylation of lamin A, resulting in progerin (Capell et al., 2005). This cryptic splice site is only partially activated and it is estimated that only 10-50% of splices mRNA in transcribed. Since the second LMNA allele is normal, there is still some presence of wild-type lamin A although it is present in much lower levels. Whilst most HGPA pat ients are heterozygous for LMNA p.G608G, mutations have been reported on other location on the LMNA gene, such as one patient with a p. E145K mutation and another with 471C and R527C mutations (Goldman et al., 2002). These mutations have lead to various laminopathies very similar to HGPS (often referred to as atypical HGPS) however the pathophysiological manifestation of these diseases is probably different as they do not result in the production of progerin. HGPS cells are significantly larger than normal cells and usually have large cytoplasmic vacuoles, an abnormally shaped and sized nucleus, often distorted with chromatin extrusion (De Sandreà ¢Ã¢â€š ¬Ã‚ Giovannoli et al., 2003). Goldman et al. (2004) also report evidence of misshapen nuclear envelopes and abnormally thick lamina, both of which are associated with other mutations on the LMNA gene. Not surprisingly, these structural abnormalities cause a variety of cellular dysfunctions including loss of structural nuclear integrity and certain mitotic problems such as irregular chromosome separation, delays in cytokinesis and nuclear assembly and binucleation (Dechat et al., 2007). The loss of nuclear integrity can have a detrimental effect of the function of the cell, however it does not remove all structural ability of the nucleus and cell, it only reduces it. This means that the tissues most likely to be affected by a comprised nucleus are those which are consistently subjected t o mechanical stress, such as blood vessels. Indeed, vasculature in HGPS patients is often severely compromised and death is almost always caused by heart failure. HGPS cells have abnormal chromosome organization in interphase nuclei and can show a loss of peripheral heterochromatin, possibly due to various epigenetic changes. These include upregulation of genes such as H3K9me3 and H4K20me3, both of which are involved in the definition of constitutive heterochromatin (Columbaro, 2005). The H3K27me3, responsible for the definition of facultative heterochromatin, is downregulated, possible due to a reduction in the expression of the histone methyltransferase enhancer EZH2 used for H3K27 trimethylation (Schumaker et al., 2006). Evidence has suggested that these changes in heterochromatin due to altered gene expression may often result in further changes in gene expression. An interesting line of investigation to follow would be to monitor the expression of various other genes in HGPS cells. It is important to understand if HGPS enhances or inhibits the expression of various other genes and, if so, what these genes are and whether these genes play a part in the HGPS phenotype. Since lamin A only appears in differentiated cells, it is possible that one of the roles of lamin A is to maintain differentiation of the cells by securing tissue-specific gene expression. This could mean that the premature aging phenotype is not actually related to normal physiological ageing, but occurs due to certain tissues being unable to perform their designated function due to incorrect gene expression, leading to cell death, tissue degeneration and organ failure. Several studies have indicated that HGPS cells show increased damage to DNA. This was demonstrated by Bridger and Kill (2004) whose experiments showed that HGPS cells were unable to proliferate sufficiently when kept in culture and showed increased rates of apoptosis as well as demonstrating early signs of cellular aging. All of these afflictions are caused by damage to nuclear DNA. Liu et al (2006) also demonstrated that HGPS cells have increased activity in their DNA repair pathways, strongly implying that DNA damage has occurred. The most compelling evidence to suggest DNA damage as a likely culprit for progeroid symptoms is presented in a study by Liu et al. (2005), which showed that HGPS cells have a double strand break (DSB) repair defect. These cells show less concentrated levels of DSB repair factors such as Rad50 and Rad51 as well as damage signaling molecules such as 53BP1. With this evidence, the conclusion can be drawn that Lamin A in necessary for complete DNA repair to take place when necessary, and also that DSB repair is diminished in HGPS cells. DSBs are the most dangerous type of DNA damage that can potentially occur as a result of the constant attack from various agents, as they can potentially result in loss or confusion of genetic information or cell death. To some extent, DSBs occur naturally within the body during normal processes such as meiosis (Keeney Neale, 2006), or during replication when the separated stands encounter blocking lesions. The level of DSBs that occur during these processes can be increased by UV radiation, ionizing radiation, various chemical agents and the presence of free radicals. When a DSB occurs, the cells defense mechanisms commands that the cell cycle halts and DSB repair mechanisms activate. DNA DSB repair mechanisms are thought to occur as one of two processes: Non-homologous end joining (NHEJ) and homologous recombination (HR). Although HR is thought to be considerably more accurate than NHEJ, neither mech anism will produce perfect results. Evidence has been presented to imply that as we age we become increasingly dependent on HR to repair DSBs as activity of NHEJ and all other mechanisms gradually decrease (Johnson-Schlitz Engels, 2006). Many of the changes to the nuclear membrane are not a direct result of insufficient lamin A, but instead are caused by the presence of Progerin, an abridged version of lamin A, and its accumulation of the INM. This accumulation results in alterations in the structure of the nuclear lamina. Liu et al. (2005) suggests that the inefficient DNA repair mechanisms which occur in HGPS cells are in fact due to raised levels of Progerin at the INM. Fitting with this theory, experiments designed to reduce the levels of Progerin have successfully managed improve the cellular phenotype of HGPS cells. Scaffidi and Mistelli (2005) proposed inhibiting the production of Progerin whilst leaving lamin A unaffected by using specific antisense morpholinos which inhibit splicing at the deviant site. Another approach is to treat HGPS cells with farnesly transferase inhibitors (FTIs) which, as the name suggests, inhibit farnesyl transferase, so preventing the modification of Progerin to the farnseylated ki nd seen in HGPS cells. Liu et al., (2006) have shown that this approach does not only improve the cellular and nuclear abnormalities of HGPS cells, but can actually improve the health of HGPS mice. However, FTIs are not specific to Progerin as antisense morpolinos are, and lamin A is likely to be inhibited as well as the modification of Progerin. It is also possible that several other unrelated proteins would be affected by this approach; however these negative side-effects have not yet been documented. Several potential cellular and molecular mechanisms which may contribute to the HGPS phenotype are described below in figure 4. Figure 4 Various cellular and molecular mechanisms which may contribute to the HGPS phenotype. Progerin becomes trapped within the nuclear membrane as a result of permanent farnesylation. Alteration of the normal lamina structure causes vulnerability to mechanical stress and some nuclear blebbing. Other consequences involve disruption of protein interactions, disorganization/loss of heterochromatin and disrupted interactions with RNA polymerase II, RNA splicing factors and transcription factors, causing misregulation of gene expression. (Coutinho et al. 2009) The way these cellular abnormalities cause the general HGPS phenotype are not yet understood and currently can only be speculated on. As further research is carried out regarding HGPS, the cause of premature aging throughout the whole body may become more transparent. Treatment Due to the rarity and complexity of HGPS, there is currently no known cure; however, there are a variety of treatments aimed at alleviating the symptoms which are associated with this disease (Progeria Research Foundation, 2006). It is recommended that patients suffering from HGPS have a regular and nutritional diet as well as supplementary vitamin tablets (in normal doses). Dental problems which occur as a result of HGPS are treated with fluoride supplements, and aspirin should be administered on occasion in order to reduce the risk of heart attacks and strokes, which are invariably the main causes of death in HGPS children. In the case of heart-related problems such as angina, drugs like nitroglycerin may be used, although the dose should be measured carefully based on weight and height as use of anesthetics on children can be potentially dangerous. There is little that can be done to reduce the effect of reduced bone mass except for vitamin and calcium supplements, so children sho uld be accompanied at all times as they are at significantly greater risk of fracturing bones. The hip bones are particularly susceptible to dislocation due to coxa valga. Certain surgical procedures can take place to reduce the risk of this, as well as physical therapy in order to keep all joints as mobile as possible. The use of growth hormones has been suggested as a potential treatment for HGPS children; however the long term effects of this have not been shown to be significant. Currently there are several areas of research into possible clinical therapeutic treatments for progeria. Wang et al. (2008) and Liu et al (2006) demonstrated the use of farnesyltransferase inhibitors (FTIs) which appear to reduce the nuclear abnormalities present in HGPS cells, reducing the severity of symptoms on HGPS mice, improving their general health. Subjects showed improved cardiovascular health, a reduction in the number of bone fractures and improved survival and growth rates. This has been substantiated with evidence from Toth et al (2005) who showed that human fibroblast cells expressing progerin had reversed nuclear alterations when treated with FTIs in vitro. Clinical trials testing the effect of FTIs in children with HGPS began in August 2009 and ended the following December. Results from these trials are still being awaited. Summary Most of the breakthrough discoveries regarding HGPS have been made within the last few years. These include the location of the HGPS mutation, the nature of the disease and potential clinical therapies which are aimed at preventing the HGPS phenotype on a cellular and molecular level instead of simply treating the symptoms. There are several ways that the effects of the point mutation on the LMNA gene on chromosome 1 could lead to the pathogenesis of HGPS and it is likely that the combined affects of this mutation results in the HGPS phenotype. Compromised nuclear integrity may lead to reduced structural support for the cell, so those tissues under constant mechanical pressure such as the vasculature will suffer more greatly than other tissues. Another possible cause of the HGPS phenotype is the accumulation of DNA damage. This is a logical conclusion to draw, as the mechanism of normal human aging is thought to occur in this way. HGPS cells have insufficient DNA DSB repair mechanisms and so the phenotype of premature ageing in children with progeria is simply due to the magnification of one of the factors that causes aging in healthy humans. The pool of stem cells that healthy humans rely upon to counter increased apoptosis as a result of DNA damage would be under more pressure to proliferate in HGPS children, perhaps exhausting supplies and causing tissue degeneration. It is also possible that the stem cells themselves are affected by the HGPS mutation, causing a decline in proliferative ability. The possibility that the HGPS mutation may lead to up or down regulation of other genes is not one that should be ignored. If this is the case, the vast variety of symptoms which accompany HGPS may be explained by the altered lev els of expression of other genes. Until more is understood about Hutchinson-Gilford progeria syndrome, it is impossible to conclusively explain the extraordinary symptoms of this disease. Perhaps the results of the recent clinical trials will shed more light on how the alteration of two proteins due to a single point mutation can cause a child to show such drastic physiological aging. Experimental data analysis Programmed cell death (PCD or apoptosis) is a necessary part of complex life in all sorts of multicellular organisms. In humans, it is not only essential during embryonic development (preventing all manner of deformities) but also consistently through life. Efficient apoptosis prevents a vast number of diseases by ensuring that any unnecessary or potentially harmful cells are destroyed safely, without harmful effects on neighbouring cells, which happens in necrosis. Apoptosis only causes a diseased state when its rate of action exceeds or falls short of that which is necessary to keep an individual healthy. Insufficient apoptosis is well known culprit for the development of cancers, when tumorous cells which should have been erased are allowed to proliferate and develop into tumours. Another well known example of diseases due to lack of apoptosis is the vast number of immunodeficiency diseases caused by self-targeting T and B lymphocytes. These cells should have been removed through apoptotic signals, but when these signals fail these self-targeting lymphocytes are allowed to survive and will target the bodys own tissues. Increased rates of apoptosis throughout the body are commonly observed in many diseases, for example, HGPS. Abnormalities either within or external to the cell cause apoptotic signals to occur, resulting in PCD of cells which would otherwise not have been destroyed. PLAC8 (placenta-specific 8) is a gene which encodes a small, highly conserved protein known as onzin. Experimental evidence has been presented to demonstrate that under expression of endogenous onzin results in reduced cell proliferation, whilst over expression results in an increased cell count (Rogulski et al, 2005). This data suggests that onzin has a negative effect on the rate of apoptosis. Li et al. (2006) suggest that expression of onzin within a cell protects it from apoptotic signals and that when onzin levels are depleted the cell becomes sensitive to apoptotic assault. To test the effects of onzin on the rate of apoptosis, CEM-C7 T-leukemic cells were transfected with either an expression construct containing PLAC8 or pcDNA3, where the pcDNA3 vector acted as the control. Cultures of these cells where then exposed to a range of apoptosis-inducing agents: Fas, Dexamethasone (dex), cisplatin, butyric acid, okadaic acid and UV exposure. This was in order to determine whether expression of the PLAC8 gene effectively reduces the rate of induced apoptosis. Cell counts were taken after 24, 48 and 72 hours. The significance of the difference between cell counts in PLAC8 and pcDNA3 cultures when exposed to all apoptosis inducing agents was determined using a two-sample T-test. The samples used in each test were the apoptosis-inducing agent transfected with PLAC8 and the same apoptosis-inducing agent transfected with pcDNA3. The results from these two-sample T-tests are shown below in table I. Table I. Apoptosis inducer p-value (24 hours) p-value (48 hours) p-value (72 hours) Dex 0.023 0.069 Cisplatin 0.026 0.045 0.042 Butyric acid 0.003 Okadaic acid 0.03