Othello and jealousy Essay

Jealousy takes many forms and sometimes it is harmless while at other times it can be destructive. In William Shakespeare’s play â€Å"Othello† a man named Iago hates and is jealous of the protagonist Othello because Othello has not promoted him to position of Lietunant, so he decides to try and kill Othello. However, he first convinces Roderigo to help him because Roderigo is in love with Othello’s wife Desdemona and Iago promises that he can get him together with Desdemona. With Roderigo’s help, Iago is able to plot a series of events which eventually leads to convincing Othello that Desdemona is having an affair with Cassio, and this not only causes conflict between husband and wife, but leads to Othello’s desire to kill Cassio. Thus, Shakespeare suggests that when people are conflicted with jealousy, they may hurt others and even cause their own destruction. At the beginning of the play, Iago feels jealous towards Othello and tells Roderigo that â€Å"I hate the Moor: And it is thought abroad, that ‘twixt my sheets He has done my office: I know not if’t be true; But I, for mere suspicion in that kind, Will do as if for surety.†(1.3.12). Iago first states that he hates Othello for passing him over for a promotion but he hears rumors that his wife Emilia might have had a fling with Othello. Even though Iago is not sure if the rumors are true, he still decides to try and disrupt Othello’s life. This reveals the buildup of jealousy and hate within him, and even without any clear reason to disrupt Othello’s life, he feels the need to do create evil rumors about him in order to ruin his reputation. Moreover, Iago manipulates Roderigo in order to cause confusion and cause jealousy in Othello’s mind. Iago tells Roderigo that â€Å"Thou art sure of me. Go make money. I have told thee often, and I re-tell thee again and again, I hate the Moor. My cause is hearted: thine hath no less reason. Let us be conjunctive in our revenge against him.† (1.3.358). Roderigo is jealous of Othello marrying Desdemona, the woman he loves and is now blinded by love so believes whatever Iago tells him. Indeed, Iago se es this opportunity and decides to take advantage and use Roderigo to plot a series of events that will lead Othello into Iago’s trap. Shakespeare shows that due to Iago’s evil and jealous nature, he does not want happiness for anyone and therefore uses people as tools or toys for his own purpose. Finally, Iago uses Cassio and Desdemona to make Othello think and suspect that Desdemona is cheating on him. Iago thinks to himself  Ã¢â‚¬Å"if I can fasten but one cup upon him, with that which he hath drunk to-night already, He’ll be as full of quarrel and offence as my young mistress’ dog.†(2.3.9). Iago gets Cassio drunk so he will get in a fight because he wants Cassio to be in trouble with Othello and while that is happening he knows Desdemona will intervene and try to help Cassio. Iago’s actions show that he is so jealous of Cassio’s position that he is willing to do anything to make Cassio look suspicious. Iago’s capability to portray Cassio as unreliable and untrustworthy reveals the extremes people can go to because of jealousy. Iago is willing to exploit everyone j ust to get even with Othello proving that jealousy can actually lead humans to abandon their logic. As Iago’s plans to get Cassio killed continue, he successfully creates the seeds of jealousy in Othello too. Ironically, he even says to Othello that â€Å"O, beware, my lord, of jealousy; it is the green-eyed monster which doth mock the meat it feeds on† (3.3.15). Iago pretends to be on the side of Othello and warns him not to be too jealous because it will lead to self-destruction. As a result, Othello naively trusts a person who is trying to lead him into self-destruction yet he does not realize this and continues to step on the traps that Iago sets up. Moreover, Othello falls deeper and deeper into Iago’s master plan and begins to doubt Desdemona even though he at first wants proof of her affair. Othello reminds himself â€Å"No†¦my wife is fair, feeds well, loves company, is free of speech, sings, plays and dances well; where virtue is, these are more virtuous: †¦No, Iago; ill see before I doubt; when I doubt, prove: and on the proof. There is no more but this, away at once with love or jealousy!† (3.3.31). Othello refuses to be destroyed by jealousy because he can clearly see that Desdemona chose him out of love and not because of anything else, but he feels like he needs proof from Desdemona that she is not cheating on him to be truly convinced. This passage shows that even though Othello claims that he will not be conflicted by jealousy, step by step he is moving away from his claim and becomes jealous and filled with doubts. Shakespeare warns that jealousy has the capacity to make a person forget the reality and see people and situations clearly because it is such a strong emotion Finally, Emilia warns Desdemona about Othello’s jealousy as she says â€Å"but jealous souls will not be answer’d so; / They are not ever jealous for the cause, / But jealous for they are jealous: ‘tis a monster/ Begot upon itself, born on  itself.†(3.4.3). Emilia understands that jealousy is like a â€Å"monster† that comes out of nowhere and becomes worse and worse over time. This suggests that Othello’s mind is being controlled and taken over by the â€Å"monster† and the jealousy in his mind can keep growing until it is finally out of control. In Othello’s time, men owned women and an affair would damage a man’s reputation and ego more than today. Since Othello is a Moor, the thought of his wife cheating on him is even worse than if he was Venetian since Desdemona is his and she owes him loyalty. Near the end of the play, Desdemona discovers that her handkerchief is missing and asks Emilia where her handkerchief is. Emilia does not know and Desdemona says â€Å"Believe me, I had rather have lost my purse / Full of crusadoes: and, but my noble Moor / is true of mind and made of no such baseness / as jealous creatures are, it were enough / /to put him to ill thinking.† (3.4.7). Desdemona knows that the handkerchief is an important gift from Othello and losing it might cause doubts in Othello’s mind about her loyal ty. Unfortunately, Othello is set up by Iago and finds the handkerchief and is now convinced of his wife’s unfaithful character, so he murders Desdemona. After strangling Desdemona he says â€Å"Behold, I have a weapon; / a better never did itself sustain / upon a soldier’s thigh: I have seen the day, / that, with this little arm and this good sword, / I have made my way through more impediments / than twenty times you stop: but, O vain boast!† (5.2.55). Othello understands after killing her, that Desdemona’s death was pointless as he is now alone without the love of his life. By the time Othello realizes that he was set up by Iago and Desdemona did not cheat on him, Othello cannot tolerate the guilt of killing her and decides to commit suicide. Before stabbing himself he says â€Å"speak of me as I am; nothing extenuate / nor set down aught in malice: then must you speak / of one that loved not wisely but too well; / of one not easily jealous, but being wrou ght / Perplex’d in the extreme.† (5.2.341-345). Othello becomes the victim of Iago’s cruelty because he is unable to control jealousy, and he ends up being his own worst enemy as his jealousy becomes so powerful that he kills because of it. Shakespeare shows that jealousy can destroy not only others’ lives but can lead to one’s own self-destruction as people cannot see clearly and think rationally when they let such a strong emotion over-take them. Therefore, Shakespeare warns readers that they must control the jealousy in their lives because if they  do not, they will destroy the relationships with those around them and themselves. Jealousy is one of the strongest emotions and it can come easily when a person feels like they deserve better, as Iago does, or when they are too possessive over another person, as Othello is over Desdemona. Either way, jealousy causes people to misread reality and act irrationally.

A Definition of the Word Trust Essay

When you think of a very special quality everyone should have, trust is the first thing that comes to my mind. Being able to trust someone is very important. We have to trust people in our lives every single day. Trust helps us to have relationships and friendships. Trust is defined as believing in someone in the dictionary. Although this seems simple, it is not that easy to understand and comprehend. Trust has a deep meaning as we continue to grow and change in life. We go through many things that make us change as we live, grow, and experience different challenges. Trust is believing in someone with your whole heart and believing that he or she will take care of it or appreciate it. There are so many types of trust. Three type of trust are: trusting in a family member, trusting in someone special, and trusting in friends. With our family members, we have deep trust. They have been through everything with us and most of deep dark secrets. They have been there for us during the good times and the bad. They watched us go through elementary, middle and high school. Your family has been there to watch you mature and become the person you are today. We have deep trust with them because they took care of us when we were sick or needed someone to cry on. Since we tell them everything, we are the most attached to them. They know when we are acting strange or weird and can tell when we are sad or ecstatic. They share all kinds of memories with us and understand what and where we have been. We let family know almost everything about us. We go back to them when we have nowhere else to go. We trust them with our lives because we know no matter what, that they will always love and care for us. Another kind of trust is trust in someone special or someone that we think is our true love. See more:Â  First Poem for You Essay We tell them everything about us because we believe that they really care. We tell him or her things that we keep to ourselves because we believe that he or she has committed to us. It takes a lot of time to have this kind of trust in a relationship. It takes a lot of time to confide our secrets and personal issues in someone else. When you have such a deep trust with him or her, there should be no secrets. There are no secrets when you truly love each other. This kind of trust is just part of the commitment to each other. In this commitment, you trust each other to be faithful, respectful and to always be there for each other. Another type of trust is the trust between friends. We let our friends know about some of our secrets. We keep the deep dark ones away from them. We also try to hide our past and do not trust them right away because we have had friends in the past betray and hurt us numerous times. We do not trust them right away because we do not know about their life or their past. We do not know where they come from or what they believe makes a good friend. So we as humans hide our feelings and do not trust them. It is only when we spend a lot of time and slowly open up to each other that we become closer and can eventually trust them. Trust cannot be given. It has to be earned. It is not as simple as believing. Trust is earned. When you earn trust, you realize that you can tell him or her anything and they will still be there for you. Trust is not easy to earn though. You have to really believe in the other person and know that they will not let you down. Therefore, trust is very important to humans everywhere. Trust is a huge factor of unity and without it people cannot live in unity. Only you can fully understand trust in your own way. Trust is having a special place in their heart and you having special place for them. Finally, trust is the base for all relationships and friendships. Without trust, we cannot find the true meaning of life. Trust is a must for everything in life.

Sophomore English Exam Study Guide

The Glass Menagerie- By: Tennessee Williams Setting- After the Great Depression, before World War II; 1937 In SST. Louis, Missouri The Way Tennessee Williams broke away from straight realist staging: 1 . Had his major character also be the narrator (Tom Winnfield) 2. Incorporated a screen device into his plays to emphasize important details and actions on stage 3. Removed props 4. SE of lighting Problem with memory play: Details could be omitted or left out; biased, exaggerated details Symbolism- a person, place, or object that has its own meaning but can suggest other meanings as well Genre- Tragedy 3. Death off Salesman- By: Arthur Miller Genre- Tragedy Setting- Late sass's; Brooklyn- Present; Boston- Flashback Tense- Past and Present Protagonist- Wily or Biff Loan Antagonist- Wily or Biff Loan American Dream- an antagonist dreamThis play attacks the materialistic aspect of the American Dream He believes the achievement of wealth and success without integrity Background information is given through flashback Flashback- action that interrupts to show an event that happened in an earlier time which is necessary for understanding Expressionism- when an artist distorts reality to create an emotional effect Parental Dilutions- parents who have high expectations set for their children 4. A Streetcar Named Desire- By: Tennessee Williams Setting- New Orleans, Louisiana; sass Protagonist-Balance Dubos Conflicts 1. Balance Vs..Self 2. Balance Vs.. Stanley II. Short Answer The Glass Menagerie Techniques to break away from straight realistic staging 1. He had his major character also be the narrator (Tom Winnfield) 2. Incorporated a screen device into his plays to emphasize important details and actions on stage Key words he would want the audience to recognize 3. Removed props Distracting; Allows to concentrate more on character plot 4. Use of lighting Dimmed the lights; Low and hazy; Memory play Tennessee Williams used 4 different techniques to break away from straight realistic tagging and make his pays different than others.First, he made his main character in the play also be the narrator. In The Glass Menagerie, Tom Winnfield is both the main character and the narrator because it is his memory and told from his point of view. Also, he eliminated the use of props in some scenes. Williams believed props were a distraction and taking them away would help the audience focus on character development and plot. Tennessee Williams also used a screen device. The screen device displayed several words he would want the audience to recognize to guide them to think or feel a certain way.Lastly, he dimmed the lighting to create a hazy look. This lighting effect would help the audience remember the play was from memory. Death of a Salesman Techniques to distinguish past from present/reality from illusion 1 . Stage Directions/ Setting 2. Character's Appearance and illusion. These techniques include character appearance, setting change, and stage directions. For example, young Wily Loan was very fast moving and energetic. However, old Wily Loan is grumpy, slow moving, and dull. An example of setting change would be from the Loan's household to either Boston or a football field.Incorporated with setting change is stage directions. They indicate when the setting changes. For example, in the past, the Loan household was surrounded with many trees, leaves, and beautiful scenery. However, in the present, the house in surrounded by apartment buildings and the mood is dark and dull. Streetcar Named Desire Difference between this play and The Glass Menagerie with regards to the theme of illusion as an approach to reality The Glass Menagerie is hazy and filtered based off of memory. A Streetcar Named Desire is crude and more forward to reality. The Merchant of VeniceConflict/Resolution The conflict in The Merchant of Venice is that Bassoon is poor and needs Antonio help him woo Portia. Antonio can only turn to Shylock, who is Jewish and thus hat ed. Antonio has to sign away a pound of his flesh as a guarantee on Bassoon's loan. Bassoon finally gets a go at Portia, but he's got to pick the right casket. The resolution occurs when Portia reveals everything and Antonio is rich again. Portia accepts Notation's apology and goes even further, ensuring that, even if he's lost his friend, he's got his money back. Ill. Long Answer 1 .Tragedy/Tragic Hero (A Streetcar Named Desire/Balance Dubos by Tennessee Williams) Balance Dubos is a tragic hero because she has a tragic flaw that ultimately leads to her downfall. Blanches flaw is her inability to accept reality or where she is right now. She lives her life in illusion to escape her reality. However, she is forced to face reality after her sister's husband, Stanley, raped her. After this occurrence, Balance starts to go crazy and insane. She is sent to a mental institution. 2. Characteristics of a One Act Play (He Said She Said by Alice Greenberg) Origin- may be traced to the very be ginning of dramaUnities- conform to the Classical Unities of drama developed by the philosopher Aristotle; unity of time, unity of place, and unity of subject Unity of Time- He Said She Said takes place within 24 hours Unity of Place- He Said She Said takes place in one setting, the Helmsman' household gossiping Time- usually between 10-40 pages long He Said She Said is 16 pages long Setting- one scene He Said She Said all takes place in the Helmsman' living room Plot- simple; one of the most important elements to any play is conflict Gossiping Characters- differ from full-length plays in their scope; fewer characters or a more impel setting; focused on a main character and a single incident or goal; little time for subplots; usually 4 or less characters Felix, Enid, Mrs..Packard, and Diana Exposition- most avoid extensive exposition In He Said She Said, it gives the background information that Felix and Enid Hellman have a great relationship. This is necessary for proper understand ing because the plot is relevant Subtext- unspoken thoughts and motives of the characters?what they really think and believe; seldom breaks through the surface of the dialogue except in moments of extreme conflict; gives the performers something o do] Stage Direction- contains simple and direct stage direction 3. Motivation (Wily Loan/Death of a Salesman) Wily Loan's death in Death of a Salesman is a result of his motivation.His motivation was his want to provide and supply for his family, and also his want to prove to Biff that he was right. Wily knew that if he died, his insurance money would be given to his family so they could live good, happy lives. Also, Wily wanted to prove to Biff that he was right about being personally attractive and liked was all that mattered. Through his death, Wily was hoping to show to Biff that he was right by a on of people showing up to his funeral. Also, Wily died with a sense of personal dignity, believing he was right all along. 4. Contribution of a Minor Character (The Glass Menagerie by Tennessee Williams) Jim O'Connor, a minor character in The Glass Menagerie, helps contribute to the character development of Laura.Although he may be a minor character, his role in the play is necessary for plot development. He is the most realistic character in the entire play. He is a symbol of hope for Laura. Jim is the person that Laura and her family having been waiting for their whole lives because everything will change. 5. Dynamic and Static Character (A Streetcar Named Desire by Tennessee Williams) Balance Dubos is a dynamic character in A Streetcar Named Desire. In the beginning, she used illusion to escape her reality. However, by the end of the play, she is forced to face reality when Stanley rapes her. From that point on, she was never the same. She went from being somewhat normal to completely insane.Stanley is a static character because throughout the play he remains the same. From start to finish, he is very aggressive and never liked Balance. 6. Foil Character Merchant of Venice is a comedy because it fits the characteristics 1 . Young lovers struggling to overcome obstacles 0 Jessica and Lorenz are madly in love and want to be together, but Jessica father, Shylock, is trying to do everything he can to keep them from marrying. Also, Bassoon and Portia marry. 2. Mistaken Identity 0 Jessica deceives her father when she disguises herself as a boy and runs off to marry Lorenz. Portia cross dresses as a male lawyer and shows up in the courtroom to defend Antonio 3.Clever plot twist with multiple plot lines 0 2 main plots: Bassoon's adventure playing the lotto to win a rich wife, and Schlock's recruits of Notation's pound of flesh 4. Puns 0 Marriage; Just about everybody is married (Lorenz and Jessica) (Bassoon and Portia) Antonio is a comic hero because he has a minimal level of personal charm and worth of character who wins the audiences approval. The audience likes Antonio because he values friendship and love. Antonio is also a Christian which The Merchant of Venice favors Christians instead of Jews. Antonio is a worthy character because he risks his own life in the hands of Shylock to lend money to give to his best friend, Bassoon, to win Portrait's heart.

Using Your Manager Skills Research Paper Example | Topics and Well Written Essays - 1000 words - 1

Using Your Manager Skills - Research Paper Example First is the definition of the words used in defining the act pollutant, point source, navigable waters, and person (Manheim, 2009). Pollutant represents the solid waste, sewage, sewage sludge, biological materials, municipal, industrial, agricultural, discarded equipment and other forms of waste dumped into the water. The point source defines pipes, vessels, or containers from which pollutants are discharged. Navigable waters are water surfaces including wetlands whether or not water vessels use them. Finally, person defines corporations, government agencies, and actual people that may dump waste in water (Manheim, 2009). Secondly, the meaning of â€Å"in compliance† with the clean water act is also fundamental in understanding the act. It means that before an individual releases waste into the water, he or she must receive approval from the National Pollutant Discharge Elimination System (Ferrey, 2010). The permit provided by the agency is dependent on the individual’s waste components in accordance with the effluent limitations. The effluent limitations are limits that determine the amount and type of pollutant that can be put in a particular mass of water (Buck, 2006). This ensures that the waste dumped in particular water masses does not have a negative impact on the people that use the water. It uses technology-based standards to determine the best existing technology that every industry can use to control water contamination. For instance, it ensures that an individual has treated the waste and reduce pollutants in the water as much as possible. Additionally, the agency determines whether a particular water surface can handle any more waste products or not. Solid Waste Disposal Act deals with solid waste disposal. Solid waste includes refuse, garbage, industrial waste, and sludge from waste treatment plants. The act aims to reduce solid waste contamination in the environment by developing cost-effective and environmentally

An analysis of CSR in UK Dissertation Example | Topics and Well Written Essays - 15000 words

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Examine the development and implementation of corporate strategy in a Essay

Examine the development and implementation of corporate strategy in a regulated and competitive environment - Essay Example Its YouTube services were completely blocked in China besides other services such as Picasa, blogger etc were altered to suit the regulatory environment of the country. (LaFRANIERE, 2010) Though China has emerged as one of the leading economies with the world due to its openness of trade however, it still is a central economy. The resources are virtually under the control of government and due to ideological foundations of the country, Chinese government maintains strong control over internet, media and other channels of communication. The regulatory environment of the country therefore, sometimes, compels even firms like Google to comply with its regulations in order to operate in the region. Google has also been subject to the anti-trust laws because of its monopoly over the search engine market. EU and US governments are vigorously perusing this issue to decide the fate of Google in its primary segment of the market i.e. search engine services. This paper will discuss the developm ent and implementation of corporate strategy which Google has adapted in regulated environment of China. It will also detailed out the linkages between the competition as well as regulation while at the same time discussing the same within the perspective of Porter analysis (five forces), Sun Tzu principles, organizational structure, industry segmentation structure, competition and value chain analysis. Competitive and Regulatory Environment of Google in China Google initially started as a search engine service offering internet searching services to the users without charging them anything. Initially, it competed against the search engine services of Yahoo Inc however, due to its superior design and technology; it soon surpassed all other search engine services and became the leading service provider in the world. Over the period of time, Google has diversified itself and started to offer other services like Google Maps, online video sharing service with the name of YouTube, social networking services with the name of Orkut besides offering other paid and free services. Google’s competitive strategy has remained focused on the growth achieved through constant acquisition of new and promising businesses. Over the period of time, Google has not only grew organically but it has also been able to make some strategic acquisitions which added variety to its services besides offering it an opportunity to compete on many fronts. Google is now also planning to launch its own operating system for PCs whereas its operating system for touch screen mobile phones and tablet PCs has already hit the market. In this segment of the market, Google is facing competition from Apple as well as Microsoft with both the companies having their own operating system for mobile platforms. Despite such diversification, Google still remains the most dominating player in the search engine services and has developed a virtual monopoly over this market. Google’s primary market w as US at the start of its services however, due to expansion of its services across the globe and very nature of internet services, Google has been subjected to different regulatory environments. In a competitive environment where competition is multi-faceted, it is critical for Google to comply with the regulatory requirements while at the same time, ensuring that it remains competitive against its major competitors. (Crofts, 2009) Since external environment affects an

Industrial safety engineering (safety in work enviroment) Term Paper

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Gangs and gang behavior - week 5 Essay Example | Topics and Well Written Essays - 250 words

Gangs and gang behavior - week 5 - Essay Example Page 126 shows a list of all the problems in communities such as availability of firearms, violence and other problems. These problems lead to other problems for the members of the society, such as children as noted in page 127, for children between 12 years to 17 years. For example, it is well-known that the gang members in a society who are the most vicious and violent are usually the ones who are usually respected and praised by other members and even some members of the society. In disorganization theory, a child gets influence from existing members in the society. If the child gets exposed to such attitudes or beliefs, believing that the most violent gang member is the most respected, then this child also adopts the same trend, as noted in page 128 on risk factors. This is where the developmental theory comes in, because such a child who is under the wrong influence views the gang life as the best choice. Therefore, it is not surprising to see such a child failing in school and adopting the gangster-like behavior while trying so that he or she also gets the same respect. In chapter 5, page 119, Howell clearly states that the development theories explain more on gang joining, as part of a development process. As child, such as the one mentioned in the example who joins a gang because of influence from the neighborhood gangs is also likely to influence other children, such as his or her friends. Therefore, it becomes a development process as proposed in the development theories, because more children continue to join

Does happiness change after life events Essay Example | Topics and Well Written Essays - 1500 words

Does happiness change after life events - Essay Example Instead of focusing on the aspects of subjectivity and objectivity, which leads researchers to distinguishing a few non-reducible features which are thought to contribute to the characteristic quality of life, one should first explore the ambiguity of the very notion of quality of human life. This is based on understanding that when people speak of the human life quality, they are most likely to have different things in their minds. The main idea of the article by Richard Lucas â€Å"Adaptation and the Set-Point Model of Subjective Well-Being: Does Happiness Change after Major Life Events?† is that despite the fact that happiness levels are quite stable over time, their stability does not actually preclude important and lasting changes (Lucas, 2007). Analysis of the evidence presented by authoritative longitudinal studies disproves the widely accepted belief that having experienced important life events, individuals typically adapt. It also disproves the point raised by set-po int theorists that due to impact of inborn personality factors, people inevitably get back to happiness set points which are genetically determined. While adaptation certainly occurs, levels of happiness undergo changes, and, finally, it is vital to bear in mind that life events have their own significance. Comparison of the two articles allows identifying a range of similarities between the two studies. First of all, their central theme is happiness. While Griffin (2007) focuses on the essence of the concept of happiness as the object of the research, Lucas (2007) centers on how happiness depends on major life events and studies patterns of happiness presented within individuals’ adaptation and the set-point model of individual well-being. The theoretical background is different, however. Specifically, Lucas (2007) study of happiness patterns relies heavily on the theory of adaptation. It says that people benefit from adaptation processes because the latter protect them from hazardous psychological and physiological outcomes of lengthy emotional states. On the other hand, owing to adaptation processes people may get distracted by new changes in the environment which will refocus them from the old threats within their emotional condition. It helps individuals to overcome difficulties and get happier under certain life circumstances. At the same time, people adapt to such factors as income, health, age, marital status, as well as number friends; so these, with time, have only a small impact on their happiness rates. Besides, the theory of adaptation posits that certain variables that account for people’s happiness, for example, a well-being variable, are hereditary. It means that people may not be severely affected by life events. Some scientists have come to conclusions that happiness was the matter of adaptation (comparison of two research groups – lottery winners and those with spinal cord injury – did not find any significant dif ferences in the levels of happiness, which was attributed to adaptation). On the other hand, their colleagues found that the levels of happiness were three quarters lower in people with spinal cord injury. On the contrary, Griffin (2007) relies on a range of models to investigate the meaning of the concept happiness. Namely, he uses the perception model, objective/subjective juxtaposition, and the test model. The studies are similar in their research

International Marketing (Qasim) Essay Example | Topics and Well Written Essays - 2500 words

International Marketing (Qasim) - Essay Example The key products offered in Subway include: custom sub sandwiches, salads, soft drinks and some other food items (Ibis Report 2013). Company’s rational behind internationalization The company’s strategy is based on the aggressive international expansion worldwide. Internationalization decision is mainly based on the business growth opportunities offered by rapidly growing markets. Subway will continue to expand internationally, especially in emerging economies as it is likely to be the largest source of profit and revenue growth (Ibis Report 2013). Today, these markets include markets not yet saturated with fast food brands (Russia, the United Arab Emirates, Brazil, China, India (Fertman n.d.). Mode of entry-selection of market entry strategy to enter into various countries Subway restaurants chain has chosen franchising option as a mode of entry strategy for starting business in various countries. Initially, the Subway chain did not even select new countries to expand into, as entrepreneurs from these countries contacted Subway (Welch et al, 2008). The original foreign entry in 1986 had a following typical format: individual entrepreneurs contacted the restaurants chain from a country where there were no Subway locations, and then the development team worked together with the entrepreneur, providing assistance in opening a franchise restaurant under Subway brand (Welch et al, 2008, 61). Thus, the company transferred the method of operation to the franchisee and had a much greater degree of control over its marketing efforts in a foreign market (Lecture notes). However, nowadays, Subway is also searching actively for new markets. Business Development department of Subway determines which markets would be appropriate to entry by evaluating a number of factors, including: the cost of doing business, the GDP, fast-food development and some others, etc. By operating as a franchising chain, Subway as a franchisor experiences less risks and is capable t o penetrate various markets very rapidly. Besides the obvious benefits and advantages of the franchise concept, Subway is imposed to certain risks as well. The value of the brand, either increasing or decreasing will have effect on the franchisee competitiveness. Franchisee of Subway has a number of responsibilities, including: initial franchising fee, finding locations, hiring employees and operating restaurants, leasehold improvements and equipment and paying a fee into the advertising fund and 8% royalty to the company (Subway Global Brochure 2013, 4). Subway also has certain responsibilities, such as: providing access to operational systems, guidance on store design and equipment ordering, operations manual, training program, R&D, ongoing support and periodic audits, and informative publications (Subway Global Brochure 2013, 4). The marketing mix strategies adopted by the company There are recognized several key elements of international marketing mix, including: product support , price support, promotion/selling support, inventory support, distribution support, service support, and financial support (Lecture notes). Below are briefly evaluated all these elements with a reference to Subway restaurants chain. Product support. Even though the product line and customer service are standardized among all Subway restaurants as it is common for any franchising chain, there are cultural and local eating habits in particular country that require adaptation

Black Feminism in Britain Essay Example for Free

Black Feminism in Britain Essay Black feminism in Britain is a very strong issue. This topic could be addressed in so many ways, so I decided to address the issue through others writings. Black women have been pressing the issue of equality for a very long time now, and being black women presents a two -fold issue on equality. Being Black automatically make you a minority and being a woman takes away from your standpoint even more. This is why Hazel Carby feels that being just a feminist is nit enough; there are more issues than those that are addressed by whit feminist for the black woman. Hazel Cardy’s article White Woman Listen! Black Feminism and the Boundaries of Sisterhood, examines the way in which feminist revisionist history has reconstructed itself by appropriating the power of privilege of the historiography in order to marginalize black women in their absences and misrepresent them in their presence. In my view, it is precisely the incorporation of feminism in the worlds system and power. The concern is not one with the feminist theory and more with the misuse and abuse of black women in Britain. Black women in Britain have had a lot of battles to fight to get to where they are today, and even today they are still not equal with men in society. The black women of Britain had to not only endure migration, but hey had to also endure loosing high education positions for lower paying jobs and many had to leave their families and come to Britain alone. They did come to Britain for the fast cars and big cities; these women came over to make a living so that their families could survive. They thought that they were coming to the land of opportunity, but when they arrived in Britain they were in for a rude awakening. There the push and pull factor that is present in this situation. In the Caribbean there were little to no jobs available and that is the push factor, the pull factor is tha t in Britain there were many jobs opening up for the people. The thing that many did not know, who made this journey, was that these jobs were the jobs that the British thought that they did not want to do. This entire process alone put the Black peoples on a lower level. Being that these people were also women they were even lower than so men were. In recent reassessments of Caribbean women’s political roles both during and after slavery suggest that their leadership was crucial to popular collective action throughout Britain. Many of these women were characterized as feisty females who were used as a joke to the public. This satire reduced women’s acts of resistance to individual willfulness. The historical record to the contrary indicates that the black woman of Britain emerged in the contest of the supportive networks of families, communities, and collective work groups. This resistance soon became known as black feminism. The history of women leader in Jamaica begins under slavery, and here we are introduced to the particular spokeswoman the petticoat rebellion, which was a name from a Jamaican slave owner to show just what he thought about the Black women rising up together. Assertions of special female prerogatives and criticisms of the abuse of women had extra resonance in the British Victorian setting, with its sharp delineation of boundary between the masculine and the feminine. A crucial aspect of laying foundation for subsequent oppositional cultures in Jamaica was black women’s promotion of a popular ‘voice’ both within the missionary churches and, more radically, by forming their won Afro-Christian religious association. Thus there became a third realm of opposition other than violence and hidden resistance. There became a movement. An early public challenge to black women’s subordination is the dissenting churches occurred in the Baptist congregation. Many women of color, including those who were illiterate, participated in activities of a public and political nature through their churches, including but not limited to elections and petitions. Even the relatively conservative Presbyterian Church required ever communica nt to vote for the elders, bringing non-white men into leadership. Popular democratic procedures, and participation meetings. By literate women were perceived as a threat to the English Missionaries control over the society. Young concluded his attack on democratic procedure by noting that the Kingston petitions were a kind of test case, part of a larger agitation for popular independent control of the churches, and the society must clarify its stance on the privilege of petitioning conference ‘. By making a formal distinction between home and foreign stations, the society sought to contain not only dangerous democratic currents, but also the women who exercised the role of leadership within their churches; a major difference between home and Jamaica, after all was the degree to which women as a matter of course ‘ discussed and decided all questions brought forward. Many examples of violent language recorded in the British records were spoken by women, whether during slavery and apprenticeship, or later courthouse riots, or scuffles, whe n violence occurred, working class women were often at the forefront using insults and provocations, and weapons as well. Many of those women were black. In an earlier reference I gave the example of a slave caricature that was use to mock slaves, the urban women carried on her hard-hitting tradition of political protest. Swithin begun to trace women’s participation not only back to the plantation labor but also urban riots. Even when riots rose in religious or cultural issues, the following example show that they were always political in so far as the demonstrated black physical power and numerical strength against representatives of the state. A new urban political culture was emerging on the streets of Kingston. The Family ties have been one important aspect of some women’s participation in the Morant Bay Rebellion. Many women were accused of throwing stones at the volunteers and burning down the courthouse. Black feminist were looked at very negatively in he eye of the British from white Jamaican joke to Quasheba jokes, that ridiculed strong black women, their speech, families, and working class culture. It rest on the ideology of white women as ‘angels in he house’, whose domestic life is heaven rather than the hell that the black woman had to endure, this parody arises a question, if they have black women on record cursing, where do we find the recorded ‘voices’ of these working-class black women in the historical record? Contrary to this fake ‘voice’ the actual records of protest that have been considered in this paper suggest that black family solidarity, and community self protection with the understanding of violence against black women came most often form the wider white society. The few preserved accounts of Afro-Jamaican women’s leadership and political protest exist precisely because of the contradictory position they occupied in the colonial symbolic mapping of social order and disorder. Their words speak for themselves, while their troubled embedding in government archives, and newspapers suggest their powerful impact.

Cyber Crime Law Essay Example for Free

Cyber Crime Law Essay (a) Offenses against the confidentiality, integrity and availability of computer data and systems: (1) Illegal Access. – The access to the whole or any part of a computer system without right. (2) Illegal Interception. – The interception made by technical means without right of any non-public transmission of computer data to, from, or within a computer system including electromagnetic emissions from a computer system carrying such computer data. (3) Data Interference. — The intentional or reckless alteration, damaging, deletion or deterioration of computer data, electronic document, or electronic data message, without right, including the introduction or transmission of viruses. (4) System Interference. — The intentional alteration or reckless hindering or interference with the functioning of a computer or computer network by inputting, transmitting, damaging, deleting, deteriorating, altering or suppressing computer data or program, electronic document, or electronic data message, without right or authority, including the introduction or transmission of viruses. (5) Misuse of Devices. (i) The use, production, sale, procurement, importation, distribution, or otherwise making available, without right, of: (aa) A device, including a computer program, designed or adapted primarily for the purpose of committing any of the offenses under this Act; or (bb) A computer password, access code, or similar data by which the whole or any part of a computer system is capable of being accessed with intent that it be used for the purpose of committing any of the offenses under this Act. (ii) The possession of an item referred to in paragraphs 5(i)(aa) or (bb) above with intent to use said devices for the purpose of committing any of the offenses under this section. (6) Cyber-squatting. – The acquisition of a domain name over the internet in bad faith to profit, mislead, destroy reputation, and deprive others from registering the same, if such a domain name is: (i) Similar, identical, or confusingly similar to an existing trademark registered with the appropriate government agency at the time of the domain name registration: (ii) Identical or in any way similar with the name of a person other than the registrant, in case of a personal name; and (iii) Acquired without right or with intellectual property interests in it. (b) Computer-related Offenses: (1) Computer-related Forgery. — (i) The input, alteration, or deletion of any computer data without right resulting in inauthentic data with the intent that it be considered or acted upon for legal purposes as if it were authentic, regardless whether or not the data is directly readable and intelligible; or (ii) The act of knowingly using computer data which is the product of computer-related forgery as defined herein, for the purpose of perpetuating a fraudulent or dishonest design. (2) Computer-related Fraud. — The unauthorized input, alteration, or deletion of computer data or program or interference in the functioning of a computer system, causing damage thereby with fraudulent intent: Provided, That if no damage has yet been caused, the penalty imposable shall be one (1) degree lower. (3) Computer-related Identity Theft. – The intentional acquisition, use, misuse, transfer, possession, alteration or deletion of identifying information belonging to another, whether natural or juridical, without right: Provided, That if no damage has yet been caused, the penalty imposable shall be one (1) degree lower. (c) Content-related Offenses: (1) Cybersex. — The willful engagement, maintenance, control, or operation, directly or indirectly, of any lascivious exhibition of sexual organs or sexual activity, with the aid of a computer system, for favor or consideration. (2) Child Pornography. — The unlawful or prohibited acts defined and punishable by Republic Act No. 9775 or the Anti-Child Pornography Act of 2009, committed through a computer system: Provided, That the penalty to be imposed shall be (1) one degree higher than that provided for in Republic Act No. 9775. (3) Unsolicited Commercial Communications. — The transmission of commercial electronic communication with the use of computer system which seek to advertise, sell, or offer for sale products and services are prohibited unless: (i) There is prior affirmative consent from the recipient; or (ii) The primary intent of the communication is for service and/or administrative announcements from the sender to its existing users, subscribers or customers; or (iii) The following conditions are present: (aa) The commercial electronic communication contains a simple, valid, and reliable way for the recipient to reject. receipt of further commercial electronic messages (opt-out) from the same source; (bb) The commercial electronic communication does not purposely disguise the source of the electronic message; and (cc) The commercial electronic communication does not purposely include misleading information in any part of the message in order to induce the recipients to read the message. (4) Libel. — The unlawful or prohibited acts of libel as defined in Article 355 of the Revised Penal Code, as amended, committed through a computer system or any other similar means which may be devised in the future. SEC. 5. Other Offenses. — The following acts shall also constitute an offense: (a) Aiding or Abetting in the Commission of Cybercrime. – Any person who willfully abets or aids in the commission of any of the offenses enumerated in this Act shall be held liable. (b) Attempt in the Commission of Cybercrime. — Any person who willfully attempts to commit any of the offenses enumerated in this Act shall be held liable.

Treating Cystic Fibrosis with Gene Therapy

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

The Reintroduction of the Gray Wolf to Yellowstone Essay -- Environmen

The Reintroduction of the Gray Wolf to Yellowstone Gauss’ Law states that no two organisms can occupy the same ecological niche without excluding the other, but what happens when man gets involved with nature and tries to introduce a species where it doesn’t belong which in turn provides a second organism to fill the same niche as the first? The results of human intervention have often been disastrous for the organism that we’re supposedly helping. Humans often times do not understand the complexity of the implications that are caused directly through our intervention. In 1974, the gray wolf was listed on the Endangered Species List, and in an effort to reestablish their populations, wolves were re-introduced into Yellowstone National Park, affecting Wyoming, Montana, and Idaho (Wyoming Wolf Management Plan, 2003). Between 1995 and 1996 thirty one wolves were reintroduced into Yellowstone and thirty five wolves into central Idaho. The wolf numbers exploded, leaving these western states with the problem of wha t to do with these wolves to prevent them from exceeding their carrying capacity and where to go from here. The wolf is the largest member of the dog family Canidae, making it a real pest if it goes unchecked in agricultural systems. The wolf is one of the most efficient and effective predators in this region, preying on large ungulates; elk, deer, big horn sheep, moose, and even bison and cattle; however they will eat small mammals if there is no other food source available. Prior to 2002 estimates of the loss of livestock due to wolves were 19 cattle and 68 sheep, however in 2002, 33 cattle, 71 sheep and 1 dog were confirmed killed by wolves (Wyoming Wolf Management Plan, 2003). These kills are significant... ...88. Wyoming Game and Fish Department. (2003) Wyoming Grey Wolf Management Plan. Wyoming Game and Fish Department and Office of the Governor. (2005) Wyoming Delisting Petition. Internet Source Links US Fish and Wildlife Service http://www.fws.gov/ Wyoming Game and Fish http://gf.state.wy.us/ Montana Game and Fish http://fwp.state.mt.us/hunting/default.html Idaho Game and Fish http://fishandgame.idaho.gov/ United States Department of Agriculture http://www.usda.gov/wps/portal/usdahome Casper Star Tribune http://www.casperstartribune.net/ Wyoming Livestock Journal http://www.wlj.net/ Biodiversity http://www.deh.gov.au/biodiversity/ Wolf Updates http://www.searchingwolf.com/current.htm Wyoming Livestock Roundup http://www.wylr.net/

New England And The Chesapeake Region Before 1700 Essay -- American Am

New England And The Chesapeake Region Before 1700 Although New England and the Chesapeake region were both settled largely by the people of English origin, by 1700 the regions had evolved into two distinct societies. The reasons for this distinct development were mostly based on the type on people from England who chose to settle in the two areas, and on the manner in which the areas were settled. New England was a refuge for religious separatists leaving England, while people who immigrated to the Chesapeake region had no religious motives. As a result, New England formed a much more religious society then the Chesapeake region. John Winthrop states that their goal was to form "a city upon a hill", which represented a "pure" community, where Christianity would be pursued in the most correct manner. Both the Pilgrims and the Puritans were very religious people. In both cases, the local government was controlled by the same people who controlled the church, and the bible was the basis for all laws and regulations. From the Article of Agreement, Springfield, Massachusetts it is ...

Essay on Viscontis Interpretation of Manns Death in Venice

Visconti's Interpretation Mann's of Death in Venice Thomas Mann's "Death in Venice" is a very complex novella. To put it on screen, a director has to pick the most important (or easiest to portray) elements from the mythological, psychological and philosophical lines of the story. The plot would remain largely intact. I am most interested in the story of Aschenbach's homosexuality, so I would be concerned with the strange-looking men, Aschenbach's dreams, and the parallel between the denial of the sickness in Venice and his own denials about Tadzio. Throughout the novel, Ashenbach notices strange-looking men. The same language is used to describe the features they share. The first is the catalyst for his adventure. The traveler is clean-shaven, snub-nosed, a redhead, with furrows between his eyebrows and his teeth bared (p 4 Norton Critical). Next are a hunchbacked, scruffy sailor and the theatrical goateed ticket-taker (13). Then, the old fop in the yellow suit. He has a sinewy neck, dentures, a floppy hat, and a habit of running "the tip of his tongue around the corners of his mouth in an obscenely suggestive manner," (14). Aschenbach arrives in Venice only to be confronted with another blip on his gaydar, the gondolier. He is brutal-looking, with a yellow sash, unraveling straw hat, blonde hair, a snub nose, bared teeth and furrows between his eyebrows. He tells Aschenbach "You will pay," (18). The last strange fellow, the guitarist, comes much later on. He is emaciated, with a shabby hat, red hair, scrawny neck, beardless, p ale, a snub nose, with furrows between his eyebrows and a habit of "letting his tongue play lasciviously at the corner of his mouth." He also smells of disinfectant (50). The guitarist, like most l... ...es linger on his admirer, and Aschenbach does not seem as pathetic. The object of his affection is willing, and we lose some of the tension from the novel. Most of the mythological, psychological and philosophical references have been removed. Visconti makes Aschenbach a composer, not a writer, with a strong relationship to his (dead?) family. His character is not as fully rendered as in the novel but it is sufficient. Tadzio is probably the best part of the movie. The casting was spot-on and one can see how a grown man could fall in love with that. Some of the strange men are there, most notably the guitarist, but the repetition is not emphasized. The film shows Venice's descent into epidemic well, with the street bonfires and disinfecting of the streets. Overall the movie is almost watchable for an art film, but it does not do justice to the very complex novella.

Labouring the Walmart Way Essay

1 Always low prices. Always. This is the slogan of the world’s largest corporation, a U.S.-based retailer whose big-box stores offer a one-stop shop, from groceries to garments to garden hoses. The secret of Walmart’s success is to give consumers the lowest prices-14 percent lower than its competitors (Greenhouse, 2003)-by increasing the efficiency of the supply chain, the productivity of the labour force, and the use of labour saving technology. Competitors must adopt a similar business plan, offer something Walmart does not, or go out of business-as Woolco, Eaton’s, Simp sons, and Woodwards have in Canada (Moore & Pareek, 2004). The influence of the Walmart model is not likely to wane in the near future. With over 235 stores in Canada and plans for rapid expansion, Walmart and its effects on labour are worth considering. Are its offers of jobs, its attitude toward unionization, and its influence on industry labour practices worth the low price on the shelf? 2 One of the most frequent complaints about Walmart, which employs 1.4 million people worldwide, is its failure to pay workers a living wage. Store employees are paid 20-30 percent less than the industry average, making many of them eligible for social assistance. It is estimated that American taxpayers fork out $2.5 billion a year in welfare payments to Walmart employees (Head, 2004). Because the retailer hires hard-to-place workers, like recent immigrants, seniors, and single mothers, its employees are often afraid they will not find work elsewhere. The kind of work Walmart does offer is gruelling: stores are intentionally understaffed-the strategy behind the company’s legendary productivity gains-so that existing employees will work harder (Head, 2004). It is alleged that systemic discrimination against women within the corporation has denied the majority of Walmart workers the chance at promotion, a charge that is now the subject of the largest civil-rights suit in U.S. hi story.

The History of Mental Illness

People with depression and people who are sad are something totally different. Last y, people with schizophrenia are viewed as crazy and dangerous. For these reasons, history has viewed these individuals differently and have been misunderstood. Because of the fact that people never quite understood mental illness, undivided LULAS were often mistreated. If you had a mental illness, you were perceived as a danger to socio TTY and were immediately transferred to jail with no further questions asked. Things like HTH s are difficult to believe, but they did in fact happen in our world.People with mental illnesses ere not allowed out and were basically isolated from society only because people did not undo restart what was happening in their minds. Imagine having to face a life inside a jail cell or a public basement for most of your life. To me, having a mental illness is all too familiar so when I hear about things like this t hat actually happen in history, it hits me hard because if we re to have been born in this c entry, I know I would have been one of many to experience the categorization and the enough ionic confinement Of these mentally ill individuals.In the 1 Boob's for example, people were not vie deed as â€Å"crazy', they were viewed as being Satan. However, there were two specific individual s who began to do something about these dangerous conditions. In the sass, activist Throated Dixie fought for better living conditions for the mentally ill after witnessing the dangerous and unhealthy conditions in which many patients lived. Her initiatives created a number of a asylums, but the horrible conditions still went on. In these asylums, the rooms were so small and yet so incarcerated that a Patti .NET could not move very far.Also, doctors were not very clever in coming up with ways to treat the SE people, so they just began to make treatments up as they went on. One of the treatments that t a doctor would use is lobotomy, which essentially means that the y would drill holes into the patient's skull to examine their brain. Another treatment they would use was electroshock there app. This meant that the patient would have a helmet on their head that would transfer electricity t 0 their brain to treat their illness. A man by the name of Clifford Watching Beers lived to tell his tale.Clifford was one of many battling a mental illness. In his biography, he describe sees it as a â€Å"history f a mental civil war† which he had to fight single handed on a battlefield that â€Å"lay within the compass of his skull. † After attempting to end his life, Beers ended up getting I n trouble with the authorities and had to attend court. As his punishment, he was sentenced to attend a mental institution in New Haven. After being admitted, the attendants shaved his leg s and put muffs on his wrists for restraint.Since these attendants were incapable of understands Eng the operation of his mind and what they could not understand, they w ould seldom tolerate an y means of disobedience. Lastly, he described the bathrooms of the wards as â€Å"a room in which vehicles [were] washed in a modern stable. † After Beers came out of his punishment, he decided to begin to change the m minds of those who did not know what to do with individuals with mental illnesses. As a result, he founded Mental Health America in 1909. Mental Health America is a nonprofit organization the at helps those with mental illness.To this day, it still exists and it even provides counseling a ND treatments at no cost. Ever since then, America's viewpoint on the mentally ill have changed for the better, A way in which it has changed is that now America provides effective treatment TTS that help the individual. One of the disorders that has been very effective in treatment is De oppression. Depression is a mood disorder caused and carried on by an interaction of gene ethic, biological, psychological, and environmental factors that affect the m ind and the body. S meeting that is misunderstood by society is that depression is only feeling out of the weather .However, it is far more than that. Depression is the intensity of the feeling of sadness and a pro longed period of negative feelings. It causes a lot of argumentative behavior, aggression, and f linings of wanting to be alone. Doctors have discovered that this disorder runs in families and ca n be traced through several generations of a family. They have also found out that it is caused by a n abnormality in the way the brain produces and maintains its levels of certain chemicals that are involved in transmitting messages from nerve cell to nerve cell.To treat depression, it is v ere common for the patient to be treated with therapy sessions, but if the depression is too SST rang they will get both therapy and antidepressants. Another disorder that has been effective in treatment is anxiety. Anxiety is quiz tee normal in many people, but the way it makes it a disorder is also the intensity of it. A person w tit anxiety will most likely get many panic attacks. A panic attack is an initial frightening expel irenic of brief but intense fear that occurs out of the blue.A panic attack is most likely to happen n if the patient continues to worry about things that others would not normally care about. D actors have discovered that people with anxiety have imbalances in levels of enumerators titers. To help them, cognitive therapy works very well in patients because it challenges your thoughts and helps the patient to control themselves better. Also, some antidepressants he Ip to lower anxiety. Lastly, schizophrenia is one mental disorder that was even new for me.When found out my sister had been diagnosed with it, was very confused because I did not have any experience with this typical disorder. Schizophrenics typically hear voices that other do n to and believe that others are reading their minds, controlling their thoughts, or plotting to harm them. Doctors have no true cause, but believe that exposure to viruses and malnutrition before bi Roth can affect greatly whether or not someone can develop this disorder. Also, it has been found the t schizophrenics have less gray matter and different brain chemistry and structure.