Constructing an Argument from Multiple Sources Essay

Constructing an Argument from Multiple Sources - Essay Example The environment comprises of the settings and conditions where man, animals and plants operate. Because every person shares it, it is our obligation to ensure that it is safeguarded and maintained. Presently, the environment is threatened by human beings who live in it. Global warming is causing the polar ice caps to melt risking the existence of the habitation present there. This means that people have to willingly opt to embrace a new lifestyle so that the environment can be preserved. For instance, people can endeavor to employ less energy conserve resources that are nonrenewable as well as minimize the negative consequences that are already on earth. In his book dubbed, â€Å"life after a year of not using toilet paper† Colin Beavan supports this argument by revealing how he spent an entire year without having any impact on earth and living a life that is purely eco effective (Green para 10). A no impact transition meant any transportation that employed fossil fuel powers like taxis, elevators, and subways could not be used. The main consequence that burning fossil fuels has on the environment is the greenhouse effect or global warming. Beavan argues in his book dubbed,† no impact man†, that during the combustion of these fuels, carbon dioxide is released in the atmosphere resulting in a number of crises in the environment. For instance, the burnt fossil, releases poisonous gases like sulphuric and carbonic acids which in turn damage the environment. Consequently, this makes the environment produce acidic rain which damages the lives of both animals and life. These damaging carbon dioxide results block the proper release of the earth’s infrared radiation. Consequently, this leads to rapid heating and an increase in climate change (Beavan 73). Furthermore, the fuels emitted can erode the ozone layer that safeguards the earth from the deadly sun radiation. Fossil wastes are

Descartes Meditation Essay Example for Free

Descartes Meditation Essay 1. If Descartes’s aim is to find certainty, why does he proceed by doubting as many things as he can? He feels that as long as he goes on believing his old beliefs, laziness and habit will block him from receiving any truths. He feels that if he regards his beliefs in the same way as he does any falsehoods he can remain unbiased when judging information and only then will he receive real truths. 2. What reason does he give for doubting that the senses give knowledge? That a man asleep can have a realistic dream that he is having the same experiences as a man thats awake. 3. What does the experience of â€Å"dreams† show us concerning the senses? He talks about how real dreams appear even though they are proven to be deceiving. And if one can be deceived in a dream by all of their senses can they not also be deceived in reality by some supernatural demon. He says hypothetically that God may not have created earth, shapes, etc. and everything that we sense could be a form of deception. 4. Why can he doubt even that 2=3 = 5. He talks about the fact that he sometimes doubt others who claim to have the most perfect knowledge. And if that can be the case for them cant it also be possible for him to be wrong about â€Å"obvious† truths. Also, if one may feel that if Gods goodness would stop him from being deceived SOME of the time, wouldnt it stop him from being deceived ALL of the time since he is clearly deceived some of the time. Basically he is acknowledging the fact that he could be wrong.

Black Women clubs of denver Essay -- essays research papers

In this study you asked us to look more closely at the plight of African American women of the west and their impact on the community in which they lived. I found that most of the articles assigned were of little help in achieving this objective, in that a large amount of the articles did not give much mention of the effects of these women on their communities. However, I was able to find little bits of helpful information in each article and with the help of the article â€Å"Lifting as We Climb† (which held the most valuable information), I was able to formulate the following analyze.   Ã‚  Ã‚  Ã‚  Ã‚  African American women that are focused on in the article â€Å"Lifting as We Climb†, I believe, give a fairly accurate overview of the over all impact and ideal system that many blacks in the community held. Therefore, to understand African American women’s ideal, which invariably is a reflection of the overall black ideal system, we must first evaluate the overall stance of blacks across the nation. The increasingly large amount of racism that was being experienced by blacks across the country during the reconstruction era and later, forced the African American’s of this nation to unite under one common belief. Originally the belief was that, with the 13th and 14th amendments, blacks would soon be experience full participation in the main stream culture of white Americans. This, they would soon realize, would not be the case and so a new approach must be taken. African A...

Listening

Importance of ListeningAccording to Zarefsky, listening is important for three reasons: (1) Accuracy; (2) Feedback; and (3) Assessment.First is accuracy. I can still remember back in my 6th grade this one test given to us by our English teacher. Looking back from today, it was actually more of a listening test than a reading test. Before we begin, our teacher told us to read first the instructions before proceeding. Then she gave out this two pager test about following instructions like this:Write your name in capital letters on the upper right hand corner of the paper and underline your family name.List the top ten movies you like. Draw three stars of varying sizes and encircle the biggest star.  You get the picture. There were about 50 of these instructions! So, I hurriedly answer as much as I can since we were told that it we will be under time pressure. After just five minutes, the teacher announced that it was already time to pass the paper and I wasn’t even half-way! I protested that there was not enough time. She asked me if I was listening when she asked us to read the instructions. I said, â€Å"Of course.† To which, she replied, â€Å"Then, you should have read in the instructions that you are only asked to do item no. 1.†Second reason is to be able to give feedback. I remember one of the fights I had with my then girlfriend Donna. (Not her real name.) She was saying something and but I was too engrossed with in solving this differential equation which was an assignment due next day for Math. Of course, that got her really mad. â€Å"Are you listening?† she angrily asked. â€Å"Of course, dear,† I said. â€Å"Then, tell me what you think?† Confident that I could get away with this, I made a remark on the phrase about assignments. â€Å"Yeah, I know. It must be tough for you.These teachers are driving us nuts,† I consoled her, thinking that I can get away with it. That, of course, made her really mad. She was not talking about assignments. It was actually a sarcastic remark, â€Å"Sorry, I think I’m getting in the way of your assignments.† And so she unleashed the conclusion of the matter, â€Å"I guess I really do get in the way of your assignments. Maybe it’s now time for us to move on.† Then, she walked out on me. That one, I did get clearly, because I was listening intently: She wanted to break up with me.And that brings me to my last point: Assessment. I was able to interpret and evaluate the message. Because I was listening well that time, I understood that she didn’t mean we were ready to discuss another topic or we were supposed to go somewhere. Based on what she said and her reaction, I knew she was really mad and moving on means breaking up.Personal Listening HabitsI was able to hear Steve Murell 2007 last year (July 19, 2007) speak on Leading With the Next Generation for 25 minutes. He got his text from 1 Samuel 17:38-40 and while he was expounding on the passage, and to get the most out of his talk, I employed note-taking – a technique which, according to Nwokoreze (1990) is the stage where I would reach the maximum level of understanding. (His talk is also available as pod cast in the Every Nation World Conference (2007) website.) He introduced his talk by first saying that Saul had always been used as an example of a bad leadership but if we will examine his life, it was not all bad. If ever he did only one thing great, this is it. And that introduction really hooked me in.I his teaching, he claimed that there are principles we can actually learn from this two men of God and that is in the area of leadership. We know that Saul was a lot older than David and he is a warrior. During his time, he was able to defeat his enemy using his sword and armor. So, wanting victory for David, he suggested that he should wear it, too. The problem is David was not used to it. So, he reasoned with Saul and asked Saul t o allow him just his sling and stones. And to that, Saul agreed.If you would ask me up to now what can we learn from that, I can still tell you without even referring to my notes but I can tell you that the notes really helped me really listen and digest the message. If I had not done so, I would have forgotten it all by now as studies show that this process begins almost right way. (Scott 2002) Besides, taking good notes has been found to aid individuals in remembering what they hear. (Cuesta College Academic Support 2003)Note-taking helped me in two ways: First, it helped me to focus on the focus points of the message. In as much as I was very interested in the topic, there were times that my mind would wander away or be caught up by a particular illustration. For instance, when Steve tell that David and Saul’s story is also a picture of the church, I got lost momentarily because I got caught up in analyzing what it means. I was still figuring out all the parallelism when I heard him say, â€Å"the point is†¦Ã¢â‚¬  As if on cue, I reached out to my pen and paper and write the point.I also jot down what he said that caught me so that I could later refer back to it and meditate or savor it if necessary. There were also times when I become too reflective which is quite distracting in a way. I asked myself (because Steve asked us to evaluate ourselves), â€Å"Am I giving opportunity to those who are under to me rise up in leadership or am I too insecure a leader to let them have the spot light?† Then, he would ask another question but I was still in the middle of my reflection. So, what I did was to pause, write down what I was thinking, and jot down his next question or point and knowing why I was there – to learn how to be a better leader – helped me be effective in my note taking as suggested by Fajardo (1996) and was proven by me.Since Steve spoke for just about 25 minutes, I didn’t have a great deal of difficulty li stening to him. I’m used to attending classes where teachers would lecture for more than an hour so his teaching was actually a refreshing break. But, I must admit, though, that too long speeches or lectures literally give me a headache. Just before writing this paper, I came from a whole day academic forum where I had to listen to different speakers lecturing for at least one and a half hours each. I tell you, it was difficult, especially when they say something that is beyond my vocabulary or knowledge. I actually had a headache afterwards. Perhaps, this was due to the fact that I was already very sleepy during the middle of the third session but I still pushed myself to listen.Margaret Sanger’s SpeechMargaret, on her speech, addressed the morality of birth control as she said on her opening statements, â€Å"The one issue upon which there seems to be most uncertainty and disagreement exists is the moral side of the subject of Birth Control. He next statement reveal ed her audience: â€Å"It seemed only natural for us to call together scientists, educators, members of the medical profession and the theologians of all denominations to ask their opinion upon this uncertain and important phase of the controversy.†Sanger seemed to suggest that birth control is a moral imperative. In fact, she said that her belief is that â€Å"the discussion of the moral issue [of birth control] was one which did not solely belong to theologians and to scientists, but belonged to the people.†Ã‚   Therefore, if this is not confined only to specific groups of people but to all people, then it, indeed, is a moral imperative. To drive home her point, she even explained what moral means. According to her, this would have implications of different actions which rely on the mind and the brain and that brain development is very much linked to morality.To those who are saying that birth control is unethical, immoral, or violation of God’s law, she start ed first with a discussion on morality. According to her, it would be immoral if we are irresponsible and reckless and irresponsible in our actions. We would have the â€Å"finest kind of morality† on the other hand if we are able to think ahead about the actions we plan to take. Then, she went into the discussion of how the progress of women we opposed for the fear the they would be immoral if they were granted freedom. Then, she appealed to the church to have more confidence in them.Then, she discussed the foundations of birth control which she also accepts. She said that the only problem with this in how methods to uphold these principles were carried out. So, she suggested information dissemination which should be done directly by those in the medical field. In this may, â€Å"motherhood may be the function of dignity and choice, rather than one of ignorance a chance,† claimed the speaker.Finally, she went back again on the concept of planning ahead so that populat ion control would begin at conception instead of resorting to the killing of infants, abandoning children, and abortion which is less civilized and gives life a lower value. Then, she concluded by encouraging people that the masses are becoming wiser and have been giving enough thought for their conduct. It more people would exhibit this, she claimed that there would be less immorality.ReferencesCuesta College Academic Support. (2003). Listening and Note-taking. Retrieved February 7, 2008 from http://www.cuesta.edu/student/servs_classes/ssc/index.htmlFajardo, C. (1996). Note-taking: a useful device, Forum, 34(2), 22.Nwokoreze, U. (1990). Note-taking. English Teaching Forum, 33(2), 39-40Scott, J. (2002) The 13 Keys to Effective Listening and Note-taking. Retrieved February 7, 2008 from http://www.csun.edu/~hcpas003/Listening.html

Eric Schlosser

Halleigh Benner Dr. Wiley English 701 Section 21? Contaminated Meat Every Step Of The Way Eric Schlosser’s book Fast Food Nation, Michael Moss’ article The Burger That Shattered Her Life and the documentary Food Inc. all come together to inform people on the facts about the food industry’s contamination issue. The food industry has many slaughterhouses and meat packing industries in the United States. People never think about where there meat has come from, how it is prepared, stored, or made. Unfortunately, the sanitation of our meat from where it starts to when we eat it is appalling.Many farms now raise livestock in mass groups in dirty environments, they gather into unsanitary slaughterhouses to be killed with unsanitary utensils, methods, and machinery, the meat gets combined with other meat in filthy meat packing industries, and is then packed away for us to eat. Farms should raise cows how they used to be raised, consumers should make healthier and wiser d ecisions on their choices of meat, people need to demand better food safety standards by re-introducing Kevin’s law.The industry doesn’t want you to know the truth about what you are eating, because if you knew then you might not want to eat it, but now the truth is revealed. Our farm animals such as chickens and cattle are not raised how they used to be raised. In the documentary Food Inc. many farmers would not let the camera crew inside the chicken houses, but one woman that was interviewed did. Carole Morison said, â€Å"I understand why farmers do not want to talk because the big companies that they are controlled by can cut pay. Companies control everything about what the farmers do but Carole also stated, â€Å"It is not right what is going on and I made up my mind that I am going to say what I want to say, it doesn’t matter anymore something has to be said. † The documentary showed that her chicken house was full of dust and feces everywhere. The mass amount of chickens cooped up close together couldn’t escape from the unsanitary environment. Many chicken farms are exactly like her’s. Carole said, â€Å"This isn’t farming anymore, it is mass production. The spread of disease is more likely within these mass production chickens because Carole informed us, â€Å"Antibiotics are put into the feed, but the bacteria builds up a resistance and the antibiotics don’t work anymore. † Cattle are not any different than the chickens. The documentary Food Inc. showed viewers that feedlots contain hundreds of cows that stand ankle deep in their own manure all day long. If one cow has a disease such as, E. coli then the others will have a higher risk of getting the disease as well.The unhealthy sanitation of our food even begins when the cows and chickens are alive in their environment that they are being raised. The environment of slaughterhouses where the livestock is killed is horrific and disgusting . To hide these sickening scenes, most slaughterhouses are simple buildings with no windows to see inside. In the book Fast Food Nation, the author Eric Schlosser put on knee high boots because his host from the slaughterhouse said, â€Å"Tuck your pants into the boots, we’ll be walking through some blood† (Pg. 169). Walking through deep puddles of blood is unhygienic.If one cow’s blood is infected and is then mixed with other blood that is gathered into puddles on the ground; workers have to walk through the puddles and it can contaminate machines, utensils, or other meat that is being worked on by the puddles being splattered. Bacteria grows and spreads in moist and humid conditions. Eric Schlosser states, â€Å"The kill floor is hot and humid. It stinks of manure. Cattle have a body temperature of about 101 degrees, and there are a lot of them in the room† (Pg. 170). Bacteria thrive in these places and can be harmful to us in the long run. The process of how our meat is made is unhealthy.The article The Burger That Shattered Her Life by Michael Moss stated, â€Å"Slaughterhouses have the potential for contamination every step of the way† (Pg. 3). It all begins with the removal of the hide from the cows. Food Inc. the documentary brought up a great issue that shows the viewers that when cows come to these slaughterhouses, their hides are caked with manure. To begin, hides must be removed carefully to keep the manure off of the meat but with the commotion and the speed of the slaughterhouse process, this causes high risks of the meat being contaminated with feces.Workers and inspectors from the article The Burger That Shattered Her Life say, â€Å"Much can go wrong, workers slicing away the hide can inadvertently spread feces to the meat, and large clamps that hold the hide during processing sometimes slip and smear the meat with feces† (Pg. 3). Next before transferred to the meat packing part is the gutting station, where the intestines are removed. Eric Schlosser from Fast Food Nation said, â€Å"I see: a man reach inside a cattle and pull out their kidneys with his bare hands† (Pg. 170).After a person reads this statement from Eric Schlosser, it will make people wonder if he washed his hands before he put them back into another cattle. More than likely the worker didn’t because of the speed that the process is going. These careless actions that can be prevented can spread E. coli or other diseases to meats that could cause an entire factory to contain it because of the mixing of meat in the meat packing process. Trimmings in the meat packing industry get mixed with other meat from different slaughterhouses within the United States.For example in the article The Burger That Shattered Her Life, â€Å"Ms. Smith’s patty contained trimmings from a slaughterhouse in Uruguay† (Pg. 4). Mixing meats from different slaughterhouses is not a good idea, because their regulation s could be completely different, especially a slaughterhouse from a different country. Grinding contaminated meat can leave diseases on the machine and spread to other mixed meats that are being mixed in the same grinder. Not mixing meats and sanitizing machines and utensils, every slaughterhouse’s meat can become Grade A.Cattle and other farm animals such as, chickens and pigs should be raised traditionally, in a grass pasture with enough room for them to run around and not having to stand in their own manure. A farmer in the film Food Inc. agreed, â€Å"Having cows in a pasture; they eat and fertilize the grass, the cycle is better for the environment and for them. † The healthier the animals begin their life the more likely; their meat for us to eat will be healthier and not contaminated. The only problem with this solution is that people in this world today are more worried about money and how much they can receive.The more cattle and chickens farmers can raise in the shortest amount of time is better for them and the company, that they are controlled by. Many mass production farmers do not worry about their consumer’s health because it is sometimes seen as the consumer’s own responsibility. Consumers have the ability to choose which meat they want to buy depending on where the meat has come from. They can choose meat that was produced locally or they can read labels to trace back to a preferred and trusted factory and or company. Consumers could also buy their own cow of their choosing and have it butchered for their selves personally.However, many people do not have the time to go into detail to find out where their meat has come from, especially many do not have the money to buy their own cow and have it butchered. Another solution is to reintroduce Kevin’s law for E. coli contamination. The people have the ability notify the congress to enforce food safety standards and re-introduce Kevin’s law. According to th e documentary Food Incorporated, â€Å"Kevin’s law would give back to the USDA the power to shut down plants that repeatedly produce contaminated meat. For Kevin’s law the government is trying to fix this problem with expert inspectors but it will take a while for these experts to be hired and the process to expand everywhere in the United States. Therefore, meat contamination and geting rid of unsanitary utensils, methods, and machinery will decrease at a slow rate.In addition, in the documentary of Food Inc. it was stated, â€Å"People that ridicule the food industry can be charged because the food industry has different protections than other industries do. For example, Oprah Winfrey was sued by a Texas cattleman for demeaning a food product and for the loss of profit. Mass amounts of people need to stand up to this unfair â€Å"protection† over the food industry. One person cannot do it; many have to create a movement. Enhancing food safety programs will b enefit our lives. In conclusion, our future’s health is ultimately at stake and people need to do something to change it. The sanitation of our meat starts from the environment that the livestock lives in and takes a domino effect until their meat ends up on our plates to eat.Surprisingly people have to worry about the food sanitation in the United States, and it is sad to realize that people have to be worried about the food provided in our country. However, this issue can be resolved. Solutions such as, livestock being raised in a healthy environment by the traditional way, consumers can make better choices for their selves, and they can also stand up for the rights of being able to eat meat without worrying. Change in the food industry will change our health for the better.

Health care system in usa Essays

Health care system in usa Essays Health care system in usa Paper Health care system in usa Paper The health of a nation is the strength of the nation: indeed health is wealth. A healthy nation is a productive nation. The fortress of such a super power as our country, whether in a stable economy or vibrant military and police force, is hinged on the health status of the Public. This is why it is imperative that the government I would lead would make it a point of duty to provide safe affordable and accessible health care service for the populace we serve. This task is not without contemporary challenges. Current health policy agenda does not provide a cogent cohesive approach to resolving the health problems facing the nation. Many people complain daily about the poor nature of services they get, and its inaccessibility. They complain also that when such services are available, they are poor resulting in countless number of deaths. Â  These complaints are justified and welcome in this government. The challenge is explained by the iron triangle of health which includes access, cost, and quality. People fail to visit the hospital or attend to health care because of the exorbitant cost of treatment, as compared to other industrialized countries. These services are only accessible to those who are insured. In comparison to other industrialized nations like Japan, Britain, Sweden, France, Canada, US is rated poorly by a number of local and international health agencies including the WHO in its health care delivery service. Indicators used include life expectancy, low-birth-weight averages and infant mortality. Some people blame poor health on poor health habits: the perception that the American public’s poor health status compared to other industrialized countries is a result of their negative unhealthy health habits is false. Facts confirm this [Starfield, 2000]. According to many researches carried by different agencies, third leading cause is iatrogenic, that is, arising from medical treatment, and errors of medical investigations and diagnoses. It is because the services are poor, inaccessible, and costly that health indicators show poor performance in the US. Past governments have tried at different stages of America’s health care development to find lasting solutions to the challenge that militate against our health care services. Six times in the last century [during the First World War, the Depression, the Truman, government, Johnson Administration, the Senate in the 1970s, and during Clinton’s tenure], efforts were made to introduce some kind of universal health insurance, and each time the efforts have been rejected.. Indeed for a lasting change to the problem of health care: we need to begin with changing our orientation about the system. No doubt there are challenges; the question should be: what can we do to help assuage them? Our policies in the last few decades focus primarily on methods of financing instead of health outcomes: we need a change here. We need to rise up with a fresh fulfilling perspective on health care: the focus is not funding but directed funding. Cost and Quality The plan is to make sure that people and the government contribute to the health system that subserves. Insurance has created more problems than solve them: the safe way is to create a consensus mechanism which is economy-based. People pay some money in advance for the services they would enjoy according to their economic capacity. Government continues its system of funding the system, by providing competent health policies and sophistication of the health system. If we people complain of poor service, then we must equip the system, train the practitioners well and create systems for checks through structured medico-legal systems. Doctors guilty of offenses would be duly prosecuted.

Krispy Kreme Essays

Krispy Kreme Essays Krispy Kreme Essay Krispy Kreme Essay Krispy Kreme Doughnuts, Inc. FIN Professor XXX XXXX Month xx, xxxx History Krispy Kreme was founded by Vernon Rudolph after he purchased the famous secret recipe of yeast-raised doughnuts in 1937 from a French chef in New Orleans. Rudolph began to sell these doughnuts wholesale to supermarkets. The demand for his doughnuts grew quickly, and by cutting a hole in the wall of the factory to sell directly to customers the concept of Krispy Kreme retail stores was born. The retail concept for Krispy Kreme doughnuts allowed Rudolph to grow his factory stores to 29 shops in 12 states by the late 1950’s. When Rudolph died in 973 Beatrice Foods bought his company and expanded it to more than 100 locations and expanded the menu to include soups and sandwiches. Beatrice tried to reduce costs by changing the appearance of the stores and using cheaper ingredients. This negatively affected the company and Beatrice sold the company to a group of franchise owners. This group of owners was led by Joseph McAleer, who was the first Krispy Kreme franchisee. The leveraged buyout was completed for $24 million in 1982. The new group brought back the original recipe and logo. By 1989 the group was almost debt free and they were beginning to expand. The company CEO, Scott Livengood, took the company public in April of 2000. The share price after the first day was $40. 63. Holes in Doughnut Accounting Practices In May of 2004 Krispy Kreme announced to its investors that they should expect earnings to be 10% lower than predicted. It was at this time that the low-carb diet had taken the U. S by storm, and Krispy Kreme blamed this low-carb diet for their low wholesale and retail sales. They also announced the sales of a the Montana Mills bakery chain of 28 bakery cafe’s that had been acquired in January of 2003 for $40 million in stock. Krispy Kreme also announced that the Hot Doughnut and Coffee Shops were falling short of expectations and three of them were closing at a cost of $7 to $8 million. Krispy Kreme (KKD) stock price closed down 30% that day. Shortly after on May 25th, 2004 when the Wall Street Journal published a story about how Krispy Kreme handled is accounting for franchise acquisitions. According to the article Krispy Kreme recorded the interest paid by the franchisee as interest income for immediate profit, except that Krispy Kreme booked the purchase cost of the franchise as an intangible asset and did not amortize it. In the repurchase agreement of the 7 stores in Michigan, they allowed one of the franchises top executives to stay on with the company after the repurchase. This executive left the company shortly after closing the deal, and had to pay him $5 million in severance which Krispy Kreme also rolled into the unamortized-asset category. Krispy Kreme claimed it followed GAAP standards and had done nothing wrong. The final shoe to drop as on July 29th, 2004 when Krispy Kreme announced that the Securities and Exchange Commission (SEC) had launched an informal investigation related to â€Å"franchise reacquisitions and the company’s previously announced reduction in earning guidance†. Krispy Kreme (KK) shares fell another 15%. The revelations about the companies accounting practices and showing interest as immediate income and not amortizing the repurchased franchises but rather showing them as intangible assets alone could justify the devaluation of their stock price by approx. 45%. Couple their earnings decline and the announcement of store closings and it easily can be justified. Couple that with the fear of the unknown. If Krispy Kreme was treating their interest and reacquired franchises as they were which seems to be blatantly wrong, what else might the SEC find during their investigation? This fear would certainly drive investors away and their share price down. The facts along with its ratings being dropped by 50% of analysts to â€Å"Hold† from â€Å"buy† a few months earlier. Krispy Kreme Deep Fried and Possible Deeper Issues Krispy Kreme grew incredibly quickly in the years leading up to the nvestigation (as shown in the chart below) and then may have tried to meet Wall Street expectations through some questionable practices such as shipping more product or pulling ahead product orders, then allowing the orders to be returned shortly after for credit. â€Å"Testimony by a former sales manager at a Krispy Kreme outlet in Ohio, said a regi onal manager ordered that retail store customers be sent double orders on the last Friday and Saturday of the 2004 fiscal year, explaining that Krispy Kreme wanted to boost the sales for the fiscal year in order to meet Wall Street projections. The witness said the manager explained that the doughnuts would be returned for credit the following week once fiscal 2005 was under way† (Chin, 2005). It seems pretty clear that Krispy Kreme was using questionable methods to inflate profits. Investors also later found out that Scott Livengood (CEO), the former COO John W. Tate, and the former CFO Randy Casstevens, â€Å"unloaded more than 475,000 shares of Krispy Kreme stock for proceeds of $19. 8 Million†, (Chin, 2005) while they were fully aware sales were declining since January of 2003. During this investigation, Scott Livengood, Krispy Kreme’s CEO announced his retirement. It would seem to me that there may be some deeper issues with Krispy Kreme and if I were a shareholder I would want out, or to be certain that Krispy Kreme’s accounting mess was cleaned up. The chart below shows Krispy Kreme’s performance during the years leading up to the investigation. Krispy Kreme Re-made Fresh Today Krispy Kreme’s stock has not fully recovered, (see chart below), but as of the end of 2012 Krispy Kreme seems to have made a comeback. â€Å"Krispy Kreme Doughnuts, Inc. Krispy Kreme) is a retailer and wholesaler of doughnuts complementary beverages and treats and packaged sweets. The Company’s principal business is owning and franchising Krispy Kreme stores, at which a variety of doughnuts, including the Company’s Original Glazed doughnut, are sold and distributed together with complementary products, and where a broad array of coffees a nd other beverages are offered. As of January 29, 2012, there were 234 Krispy Kreme stores operated domestically in 38 states and in the District of Columbia, and there were 460 shops in 20 other countries around the world. Of the 694 total stores, 292 were factory stores and 402 were satellites. The Company operates in four segments: Company Stores, domestic franchise stores, international franchise stores, and the KK Supply Chain† (Krispy Kreme Doughnuts). As of close of business on Friday last week KKD traded at $14. 80, way below its heyday when the stock traded in the $40’s but it is double its all-time low. Krispy Kreme doughnuts (KKD as of March 22, 2013 When compared to its competitors Krispy Kreme’s P/E is 49. 33. This is much higher than the others but its P/S is in the middle. Krispy Kreme’s competitors are listed as Dunkin’ Brands Group, Einstein Noah restaurant Group, and Starbuck Corporation. Below is the direct competitor comparison. Direct Competitor Comparison| | | KKD| DNKN| BAGL| SBUX| Industry| Market Cap:| 989. 57M| 3. 94B| 253. 09M| 42. 99B| 384. 28M| Employees:| N/A| 1,104| 6,912| 160,000| 10. 87K| Qtrly Rev Growth (yoy):| 0. 16| -0. 04| -0. 04| 0. 11| 0. 30| Revenue (ttm): | 435. 84M| 658. 18M| 427. 01M| 13. 66B| 453. 84M| Gross Margin (ttm):| 0. 17| 0. 79| 0. 21| 0. 57| 0. 31| EBITDA (ttm):| 47. 93M| 304. 86M| 48. 46M| 2. 46B| 47. 5M| Operating Margin (ttm): | 0. 09| 0. 38| 0. 07| 0. 14| 0. 07| Net Income (ttm):| 20. 78M| 108. 18M| 12. 74M| 1. 43B| N/A| EPS (ttm):| 0. 30| 0. 93| 0. 74| 1. 86| 0. 78| P/E (ttm):| 49. 33| 39. 95| 20. 01| 30. 87| 29. 99| PEG (5 yr expected):| 1. 02| 1. 58| 0. 98| 1. 43| 1. 50| P/S (ttm):| 2. 24| 5. 96| 0. 59| 3. 13| 1. 04| | | | | Suggestions for a Krisp/Klean Future Making Doughnuts I three things I might suggest if I were the CFO for Krispy Kreme doughnuts would be to insure open communication with investors and insure them that internal auditing systems are in place. I’m sure that investors lost all trust in the previous management because of the questionable practices that were followed. Krispy Kreme needs to rebuild that trust by having open lines of communication with its investors. I would take a serious look at closing unprofitable stores, and research other markets to open more stores. Some areas may still be underperforming while others are booming. Concentrate on the areas that show better potential and take advantage of that market while it is supporting growth. Because their competitors seem to offer expanded menus I would concentrate on healthy choices for the lunchtime crowd. Everyone is aware of Krispy Kreme’s doughnuts, but I’m not so sure their other menu items are well known as an option for lunch/brunch. Other than the morning rush for doughnuts, they could make their stores more profitable with being the †go toâ€Å" spot for lunch also. References Chin, N. (2005). Krispy Kreme Dougnuts: Empty calories or empty profits? Retrieved from corporateconflicts. com/index-sb-cases-kk. html Krispy kreme doughnuts. (n. d. ). Retrieved from google. com/finance? client=obq=NYSE:KKD

The Ethics for and Against Pet Ownership

The Ethics for and Against Pet Ownership Because of pet overpopulation, just about all animal welfare activists would probably agree that we should spay and neuter our cats and dogs. But there would be some disagreement if you were to ask whether we should breed cats and dogs if all the shelters were empty and there were good, loving homes available. Animal industries such as the fur industry and factory farms try to discredit animal protection groups by claiming that activists want to take people’s pets away. While some animal rights activists do not believe in keeping pets, we can assure you that no one wants to take your dog away from you - as long as youre treating it well. Arguments for Pet Ownership Many people consider their pets to be members of the family and thus treat them with love and respect. Oftentimes, this feeling appears to be mutual, as dog and cat pets seek out their owners to play, pet or invite them into their laps. These animals provide unconditional love and devotion - to deny them and us this relationship seems unthinkable to some. Also, keeping pets is a much more humane way for them to live as opposed to  factory farms, animal testing labs or circuses use and abuse the animals. However, thanks to regulations passed by the U.S. Department of Agriculture like the Animal Welfare Act of 1966, even these animals are entitled to a basic quality of life as sentient beings.   Still, even the Humane Society of the United States argues that we should keep our pets - according to one official statement pets are creatures with whom we share a world, and we rejoice in their companionship; you dont have to anthropomorphize to recognize that the feelings are returned...let us be close and cherish each other always.   The vast majority of animal activists advocate spaying and neutering. However, most will say that the reason is the millions of cats and dogs who are killed in shelters every year, as opposed to any basic opposition to the keeping of pets. Arguments Against Pet Ownership On the other side of the spectrum, some animal activists argue that we should not keep or breed pets regardless of whether we have an overpopulation problem - there are two basic arguments that support these claims. One argument is that cats, dogs, and other pets suffer too much at our hands. Theoretically, we may be able to provide good homes for our pets, and many of us do. However, in the real world, animals suffer abandonment, cruelty, and neglect. Another argument is that even on a theoretical level, the relationship is inherently flawed and we are unable to provide the full lives that these animals deserve. Because they are bred to be dependent on us, the basic relationship between humans and companion animals is flawed because of the difference in power. A sort of Stockholm syndrome, this relationship forces animals to love their owners in order to get affection and food, oftentimes neglecting their animal nature to do so. The animals rights activist group People for the Ethical Treatment of Animals (PETA) opposes keeping pets, partially for this reason. An official statement on their website states that animals lives are restricted to human homes where they must obey commands and can only eat, drink and even urinate when humans allow them to. It then goes on to list common mistreatments of these house pets including declawing cats, not cleaning litter boxes and scolding any creature to get off the furniture or hurry up on its walk. A Happy Pet Is a Good Pet to Have The opposition to keeping pets must be distinguished from a call to release domesticated animals. They are dependent on us for their survival and it would be cruel to turn them loose on the streets or in the wilderness. The position must also be distinguished from any desire to take anyone’s dogs and cats away. We have a duty to take care of the animals who are already here, and the best place for them is with their loving and caring human guardians. This is why animal rights activists who oppose keeping pets might have rescued pets themselves. Activists who oppose keeping pets believe that domestic animals should not be allowed to breed. The animals who are already here should live long, healthy lives, cared for with love and respect by their human guardians. As long as the pet is happy and lives a life of love without undue suffering, for most people, animal rights and welfare activists alike, pets are definitely fine to have!

The Culture War and Multiculturalism in Ishmeal Reeds Japanese by Essay - 1

The Culture War and Multiculturalism in Ishmeal Reeds Japanese by Spring - Essay Example 23. 1993).† Reed consequently touches on the careerist academics as he attacks them for their complicity in relation to the Ivory Towers that served as a sign of white supremacist structure of power. From the novel, it is apparent that there is need for persons from different cultures to become involved in order to enhance in integrating with each other. In his work, Reed presents Culture war as a tool that promotes multiculturalism because it serves as the cause of conflict among individuals from different cultural groups. The satire directed at these debates not only result from Reed’s success in presenting a stinging critique especially through an analysis of the Afro-Asian towards white supremacy as well as American imperialism. In an effective manner, the author portrays how individuals defending white Western view of history focused on trafficking everything in a revisionism manner as well as a â€Å"feel-good ethnocentrism† an approach used to attribute to multiculturalists. Based on the concepts that Ishmael Reed depicts, it is right to classify the novel as a â€Å"critical multiculturalism.† The term ‘critical multiculturalism’ serves as an indication that the piece of literature is out to expose fissures, tensions as well as possible contradictory demands resulting from multiple cultures as opposed to celebrating multiculturalism in an appreciative manner. Reeds goes further to dig deep in presenting the meaning of ‘culture war’ where he present s an absurd comic potential as he insists that the real wars of the 20th century that occurred in the U.S are similar to rhetoric of cultural wars. The opening paragraph of the literary material serves in presenting the creativity of the author through presentation of an effective examination of multiculturalism as well as academia to the later emphasis on

VISUAL ANALYSIS PAPER Essay Example | Topics and Well Written Essays - 1500 words - 2

VISUAL ANALYSIS PAPER - Essay Example Thesis statement: The stylistic features in the artwork named as Fox Games, by the renowned artist named as Sandy Skoglund, prove that the artist combined different elements of art (composition), provided importance to the usage of contrasting colors (color), the decision to use light/shadow determines the artwork’s visual beauty, perspective provides depth to the theme, figures help the viewers to evaluate the differences among different figures, pose elevates the artwork from predictability to originality, and gestures provide charm to the work as a whole. One can see that unity is the basic element of composition within visual art. As this term (composition) is superimposed into the scenario of the artwork-Fox Games (see appendix-1), is evident that the artwork can be easily detached as animate objects (fox and human beings) and inanimate objects (chairs, tables, chandelier, table cloth, food etc) and enjoyed differently. Still, there is a symmetrical connection among these visual elements in general. Similarly, the sense of movement is visible in the artwork because the foxes dominate the artwork as a whole. For instance, the presence of foxes is symbolic of fast movement, and the human images/figures in the artwork are symbolic of slow movement. On the other side, the chandelier is the focal point of the artwork and this is symbolic of the division between two worlds in general. The basic pattern within the artwork proves that the artist is obsessed with curved and straight lines. For instance, the basic proportion of the room is s ymbolic of straight lines and the table cloth (curved lines) and other elements are symbolic of the wise usage of pattern within the artwork. Similarly, Skoglund provides ample importance to proportion and the same is evident in the proportionate alignment of objects in the artwork. So, it is evident that the artist provides ample importance to composition, and the

Reagan Revolution Through President Obama Research Paper

Reagan Revolution Through President Obama - Research Paper Example The security threats within and outside the State were very much demanding the unanimous outbreak of the straightforward policies of the government but the political failure to take all parties on board also worsened the situations. Similarly one of the most important historical events was the cold war. The cold war ignited the hate culture between the Americans and the Russians and there was always a fight to stop the Russians to reach the hot water sea ports of South East Asia to minimize the chance of growth and put the fence to the stance of terror and hatred towards the American state. These importunate historical events shook the American policy making strategies andaffected the people on the overall grounds. The events continue to affect the people in some form or the other (Kettle, 2011). Changes in social, cultural and technologicalaspects can cause extensive changes Inthe attitude of the people because of the fact that the nirvana of intuitiveness of the technological progr essions of the modern world candrive the whole society in way that can change the pivotal aspects of the society for example the advent of the television technology has really changed the way of perception of the masses and now there is nothing in the sense of activity in the political corridors and important aspects that is hidden from the people. The elevation of social media around the world has also changed the attitudes of people. People can become more interactive and critical towards the general regimes around the world because everything is subject for open discussion in the social media and there is nothing that can be perceived in the wrong context. The changes and advancements in technology can drive the whole society in a specific way. The policies of government in the United States have effected largely on the social and historical aspects of people because of the fact that the government policy can embark huge effects on the vicinity of the people. For example the deci sion to take part in the cold war and support the Afghans back in eighties has changed the pivotal aspects of thoughts of people now. Most of the people are of the view that supporting the people of Afghanistan back in eighties was a wrong decision which has affected every single individual of the United States in some form or the other. Similarly, the policy to fund the technology park and boost up the technology advancement in the country has supported the people’s lives, created more jobs and elevated the progress of the individuals in all the contexts. The economic policies in the times of crunches have also affected the local living standards (Tradshad,, 2013). Being the â€Å"super power† has raised many questions at the legitimacy of American State affairs because of the fact that American has been at the threat of violence and internal conflicts after the furious 9/11 attacks that took 3,000 lives of the Americans and injured numerous. The effective winning of the Cold war back in nineties and the throttling effect of the incidents after that people have given the Americans a sense of responsibility to elevate the proper manifestation of the responsibilities of the Super power entity. The lives of the common man have not beeffected by turning of the American state into super power because there are augmented threats of terror

Brightware Corporation Essay Example | Topics and Well Written Essays - 1250 words

Brightware Corporation - Essay Example Until the past 3 years, the sales of Brightware Corporation were unparalleled by any other company in the fray. In fact, our products had received maximum points as part of a general quality survey conducted by the Bureau of food standards, both in terms of quality as well as safety of use. However, there ware some serious reasons for the company not being able to perform with similar momentum during the previous year. In order to determine the exact causes of this slump, I visited a number of places associated with the company. Firstly, I spent considerable time at the warehouse facilities of Brightware Corporation to determine whether there were any lapses in terms of efficiency or quality. I met with a number of key personnel and also had performed an analysis on the efficiency at various stages of the production line. From my investigation at these facilities, I succeeded in figuring out a few key aspects that were hampering smooth supply. In this regard, I made observations that in addition to a slip in the employee morale, there was also an increased incidence of absenteeism among the personnel and this was directly having an impact on overall efficiency to the tune of a drop of 20%. The reasons for t The reasons for the fall in employee morale are not restricted to a single aspect. Firstly, upon visiting the 6 warehouse facilities of the company, I discovered that the working conditions were not up to the standards. Over the years, much of the machinery that had started to get old had not been replaced. It was also found that much of the warehousing equipment such as cranes and forklifts (almost 65% of the total equipment) required a major overhaul. The increased sales over the past few years that had grown by 125% over the past 4 years had increased the workload of the staff, who at most times, were unable to cope with the heavy demand and supply forces. This increased work pressure combined with a lack of efficient equipment has been found to be the major contributor for the fall in employee motivation. In addition to this, unable to cope with the extreme work pressure, many of the employees had been forced to absent themselves on a regular basis. In fact, a look at the attendance registers over the past years suggests that the rate of employee absenteeism had increased from a mere 6% to a staggering 15% within the span of a single year. Apart from this, as the business had grown, the supply chain had become overburdened and the lack on the part of the company to open up additional warehouses (calculations show that we require to open 4 new ones as of now) as a measure to satisfy the increased demand. Therefore, transport at the existing warehouse facilities of the company had to wait for prolonged periods, which was having an impact both on the supply from manufacturers as well as the supply to the retail chains. In fact, this has grown to such proportions that the overall productivity of our company has dropped by nearly 20%. A part of my interaction with some of the

THE BUSINESS PLAN Essay Example | Topics and Well Written Essays - 2500 words

THE BUSINESS PLAN - Essay Example We look at those management team who must have at least 10 or more years of experience on the field. The Island View Restaurant’s emphasis will be placed also on efficient management practices in almost all its functional areas of financing, directing, staffing and better decision making. Canvey Island is generally regarded to be in great need of friendly environment with excellent food and drinks. The restaurant will offer wide range of food ingredients and recipes from different countries food specialists. The Restaurant’s menu would be prepared considering wide range of food and drinks from different countries most marketed food and drinks. The restaurant would be a place where international food and drinks are provided to those who come from different areas of the world. So, our customers would be able to taste different international foods like Chinese food, Indian ingredients, Arabian meals etc. Moreover the staffs would be selected from both village and cities and will be given training programs so as to enable them prepare most quality foods and serve a friendly atmosphere within the restaurant. The target audience will be general public and rich people who generally need organic food and drinks. The targeted market includes Canvey Island population of more than 34,000 and more from other cities, islands, and even countries who visit Canvey Island. These keys of our mission will enable the restaurant achieve our mission goals. The business management primarily understand that any business can be successful only when it realizes why it is in the field concerned and what kinds of services it is supposed to provide to its customers. The priority is customer satisfaction. This customer satisfaction can be achieved by providing right service along with right information at right time and right place. We value this fundamental marketing principle. The mission is to provide great tasting food and drinks as well as to offer efficient

Brightware Corporation Essay Example | Topics and Well Written Essays - 1250 words

Brightware Corporation - Essay Example Until the past 3 years, the sales of Brightware Corporation were unparalleled by any other company in the fray. In fact, our products had received maximum points as part of a general quality survey conducted by the Bureau of food standards, both in terms of quality as well as safety of use. However, there ware some serious reasons for the company not being able to perform with similar momentum during the previous year. In order to determine the exact causes of this slump, I visited a number of places associated with the company. Firstly, I spent considerable time at the warehouse facilities of Brightware Corporation to determine whether there were any lapses in terms of efficiency or quality. I met with a number of key personnel and also had performed an analysis on the efficiency at various stages of the production line. From my investigation at these facilities, I succeeded in figuring out a few key aspects that were hampering smooth supply. In this regard, I made observations that in addition to a slip in the employee morale, there was also an increased incidence of absenteeism among the personnel and this was directly having an impact on overall efficiency to the tune of a drop of 20%. The reasons for t The reasons for the fall in employee morale are not restricted to a single aspect. Firstly, upon visiting the 6 warehouse facilities of the company, I discovered that the working conditions were not up to the standards. Over the years, much of the machinery that had started to get old had not been replaced. It was also found that much of the warehousing equipment such as cranes and forklifts (almost 65% of the total equipment) required a major overhaul. The increased sales over the past few years that had grown by 125% over the past 4 years had increased the workload of the staff, who at most times, were unable to cope with the heavy demand and supply forces. This increased work pressure combined with a lack of efficient equipment has been found to be the major contributor for the fall in employee motivation. In addition to this, unable to cope with the extreme work pressure, many of the employees had been forced to absent themselves on a regular basis. In fact, a look at the attendance registers over the past years suggests that the rate of employee absenteeism had increased from a mere 6% to a staggering 15% within the span of a single year. Apart from this, as the business had grown, the supply chain had become overburdened and the lack on the part of the company to open up additional warehouses (calculations show that we require to open 4 new ones as of now) as a measure to satisfy the increased demand. Therefore, transport at the existing warehouse facilities of the company had to wait for prolonged periods, which was having an impact both on the supply from manufacturers as well as the supply to the retail chains. In fact, this has grown to such proportions that the overall productivity of our company has dropped by nearly 20%. A part of my interaction with some of the

Mound Builders of Central America Term Paper Example | Topics and Well Written Essays - 1000 words

Mound Builders of Central America - Term Paper Example The mounds are usually shaped square or rectangular, although some hexagonal and octagonal mounds were also found (Gissing 13-14). Thesis Statement: The purpose of this paper is to investigate mound builders of Central America, examine their history, what the mounds represented, whether the mound builders were religious, and the culture and mound building of the Cahokia. Between 2000 B.C. and A.D.1600, the Indians in the ancient Midwest and South thrived for several millennia. Their settlements transformed the untamed wilderness into an advanced network of complex political and economic features. The network was often linked by waterways such as the Missippi River. The first important urban centers were created in North America by the mound builders, from Cahokia in southern Illinois to Poverty Point in northeastern Louisiana (USA Today 12). â€Å"The greatest concentration of mounds lay in the heart of the continent: Ohio, Illinois, Indiana, Missouri† (Silverberg 3). There were subsidiary mound areas in western Tennessee and Kentucky. Nearly every major waterway of the Midwest was surrounded by clusters of mounds. The mounds built in Central America and Mexico were constructed for the same purpose as those in other parts of the continent. Most of the lower mounds would have been constructed â€Å"as foundations for the more important edifices of the mound building people (Gissing 15). Many of the great buildings erected on such pyramidal foundations at Palenque, Uxmal and other places in the region did not vanish over the centuries because they were built of hewn stone laid in mortar. On the other hand, the mound builders beginning their construction works in the lower Mississippi used wood or some other perishable material; therefore there is not even a trace of those mounds to be found today. The higher mounds with broad, flat summits, reached by stairways on the outside, appear like the Mexican

Rosencrantz and Guildenstern Essay Example for Free

Rosencrantz and Guildenstern Essay Gertrude becomes shocked at what Hamlet has just done Oh me, what hast thou done? here she stands in shock. Gertrude cannot really believe that her own son has committed a ruthless murder. This can be interpreted by Gertrude holding her head in her hands and not wanting to look at Hamlet or the dead body of Polonius. Hamlet tells Gertrude what Claudius has done A bloody deed? Almost as bad, good mother, as kill a king and marry with his brother, she does not want to believe Hamlet as she says, As kill a king? Hamlet on the other hand looks at Polonius as a wretched, rash, intruding fool he pities Polonius. This is because he has always tried to get to the top by methods that have not always proved successful or helpful by indirections find directions out. Now Hamlet turns on Gertrude, he forces her down again and accuses her of having no sense of feeling If damni d custom have not brazed it so, that it be proof and bulwark against sense. He also accuses her of not knowing the meaning of marriage vows makes marriage vows as false as dicers oaths. He then compares the two husbands. He does this to show to Gertrude what she had and what she has now so she sees what a big mistake she made by marring Claudius and not seeing his true self. Hamlet regards his father as one of the Gods Hyperions curls, the front of Jove himself, an eye like Mars, to threaten and command; a station like the herald Mercury he also says where every god did seem to set his seal. Followed by him talking about Claudius like a mildewed ear. Like in many publications Hamlet will have the picture of King Hamlet around his neck in a locket and Gertrude will have the picture of Claudius around her neck in a similar fashion. Afterwards he begins to insult Gertrude about her inability to be in command of her sexual desires. Many people believe that Hamlet is so malevolent towards Ophelia because Hamlet sees Gertrude having no control over her life so he thinks that all women are like that and cannot make up their minds. Another reason is that he subconsciously loves his mother and cannot commit in another relationship. At this point Gertrude realises what she has done Thou turnst my eyes into my very soul, and there I see such black and grainid spots as will not leave their tinct. However she does not want to hear any more and repeatedly tells him to stop Oh speak to me no more. These words like daggers enter my ears . daggers is a reoccurring theme as in Act 3 Scene 3 he says I will speak daggers to her but use none. So in actual fact he achieved his goal. When the ghost appears Hamlet goes quiet and speaks peacefully. He does this as he looks up to and respects his father also he is still quite scared of him even though it is his father it is still a ghost. Additionally Hamlet is worried what it might do to him because Hamlet has been offensive toward his mother, which was not part of the plan. The ghost is dressed in armour, as he was when he was living. The ghost reminds Hamlet of his purpose and tells him to comfort Gertrude This visitation is but to whet thy almost blunted purpose. But look, amazement on thy mother sits. Oh step between her and her fighting soul the ghost says this quietly, almost whispering. This statement shows that even though Gertrude married so soon after his death, King Hamlet still cares for her. Immediately after Hamlet comforts her and asks how she is doing, his tone of voice changes completely as if something just wash over him. Very confused by what just happened she asks Hamlet Wheron do you look? this could imply that Gertrude does not care as much for King Hamlet as Hamlet as she cannot see King Hamlet. It could also mean that King Hamlet would rather not appear before of Gertrude, as he still loves her and would not want to startle or upset her. Hamlet eventually convinces Gertrude that in reality he is not mad and asks for her forgiveness. He does this as he feels, on reflection of what the ghost said, that he was very harsh to Gertrude, also he upset her and is afraid of the ghost. Hamlet subsequently requests Gertrude not to sleep with Claudius and tell him about the conversation and his antic disposition. He threatens Gertrude and becomes quite aggressive again but not as much, Gertrude again becomes a little scared of Hamlet. Gertrude subsequently reassured Hamlet that she would not say anything I have no life to breathe what though hast said to me. Hamlet reveals his plot to kill Rosencrantz and Guildenstern. He tells her this as he feels that she is on his side and he would like to remain as honest and loyal as possible to her. At this point Gertrude has been through so much she does not really take this in and so does not make much of a reaction. The scene ends with Hamlet dragging Polonius body out of the room leaving Gertrude in a solitary moment. The lights dim all is quiet and all that is heard is the rain and the scene will end with a flash of lightning and a clap of thunder. This scene prepares us for what is to come as it gives us an insight into what Hamlet is capable of. Additionally this is the first time a murder has taken place besides King Hamlets murder. This scene contains so many emotions that it is practically a play itself. I believe that the Branagh production worked the best as there was much more emphasis on the important parts of the scene although there was too much violence when killing Polonius. Also Gertrude does more to get away from Hamlet in this film than the others do as she turns away much more when he talks to her about Claudius and her failure to control her sexual feelings. His production also had more emotion to it and showed what was happening much more clearly. This play has proved so popular through the ages as it contains something for everyone, as it ranges from romance to murder. Furthermore everyone can relate to it as it has many components of real life situated within the play, this made it, and made it stay so popular. There is also much more room to interpret the script so every time you see Hamlet performed by a different company you can be assured that you will get a new play each time.

Cocaine Pharmacology and Effects on the Brain

Cocaine Pharmacology and Effects on the Brain Cocaine is a highly addictive substance abused worldwide. Its primary mechanism of action involves blockage of dopamine, norepinephrine and serotonin transporters in specific brain regions, mainly the dopamine reuptake system located on mesolimbic neurons. Cocaine increases the dopaminergic neurotransmission and triggers adaptive changes in several neuronal circuits underlying reinforcement, reward, sensitisation and the high addictive potential of cocaine. However, the long-lasting behavioural effects associate with cocaine addiction show there is complex neurotransmitters interaction within the reward circuit. Excitatory amino acid and inhibitory GABA transmitters also play a part in these changes. Glutamatergic systems regulate dopamine function, while GABAergic modulate the release of basal dopamine and glutamate. Understanding of the molecular and cellular mechanisms that lead to cocaine addiction has given new treatment methods in the pharmacological field to develop better med icine. Especially, useful monoamine agonists treatment may be successfully in controlling behaviour and lead to long term moderation of drug taking. However, more studies are needed in order to identify safe and efficacious pharmacotherapy. Introduction Cocaine, an alkaloid derived from the leaves of Erythroxylon coca is a psychostimulant drug linked to human addiction (Dackis et al., 2001). Cocaine acts as a local anaesthetic with sympathomimetic and vasoconstrictor properties (White and Lambe, 2003). In addition, cocaine is a potent uptake blocker for dopamine (DA), norepinephrine and serotonin (Carrera et al., 2004). As shown in figure one, the chemical structure of cocaine molecule contains two rings, the six-carbon phenyl ring shown on the right and the unusual nitrogen (N)-containing ring shown on the left, both necessary for its biological activity (Meyer and Quenzer, 2005). Cocaine acts by blocking the dopamine transporter within the mesocorticolimbic reward system. Blockade of the transporter increases the level of dopamine in this region of the brain. Increased dopamine level is responsible for the euphoric effect of cocaine (Butterner et al., 2003). However, the long lasting effects of behavioural characteristics of cocaine addiction, such as sensitisation and the vulnerability to the reinstatement of drug seeking years after the acute rewarding effects of the drug have disappeared, shows that there must be complex interactions between additional neurotransmitter systems (Kalivas, 2004). In contrast to dopaminergic system, excitatory amino acid and inhibitory GABA transmitters also play a role in these changes. Glutamatergic systems regulate dopamine function, while GABAergic modulate the release of basal dopamine and glutamate (Baler and Volkow, 2006). Additionally, cocaine can also interact with several receptors and ion channels, including nicotin ic acetylcholine, and opioid receptors coupled to voltage-gated Ca2+ and K+ channels (Kobayashi et al., 2007), resulting in prolonged elevation of extracellular dopamine. The potential abuse of cocaine is mainly based on the rapid development of tolerance to the euphoric effects (Butter et al., 2003). Cocaine addiction is an uncontrollable and continually relapsing drug taking disorder (Torregrossa and Kalivas, 2008). The behavioural manifestation of addiction is mediated by adaptations that chronic administration of drug abuse elicits at the level of individual neurons in the CNS. These adaptations alter the functional properties of neurons, which in turn change the properties of the functioning of neural circuits in the brain in which these neurons are involved (Nestler, 1997). The probability that one will become addicted to cocaine depends on the method, the frequency and the duration of ones cocaine intake (Carrea et al., 2004). Historical aspect of cocaine use The use of cocaine for personal satisfaction dated back over thousands of years ago, when Erythroxylon coca, the plant from which cocaine is extracted was used by indigenous people from Andes and South America for religious, mystical, social, and medical purposes (Dackis et al., 2001). The coca leaf was chewed by these communities because of its euphoric effects and its ability to reduce fatigue and hunger and to enable sustained periods of heavy labour (White and Lambe, 2003). This leaf was introduced in Europe in 1492 by the Spaniards, when they conquered South America and discovered that this leaf would be useful for performing hard labour (Julien et al., 2008). Eventually, the Spaniards started using the coca leaf as a method of payment for the native worker in gold and silver mine, who would take the leaf to reduce appetite and increase physical stamina. Cocaine alkaloid was first isolated by a German chemist Friedrich Gaedche in 1855 (Julien, 2008). The ability of cocaine in reducing fatigue and hunger were recognised by Sigmund Freud who used cocaine himself. Freud and others also recognised the ability of cocaine to cure opioid addiction. As a result, Freud prescribed cocaine to his patients who were addicted to morphine (Boghdadi and Henning, 1997). Unfortunately, many of these patients became addicted to cocaine themselves (Grilly, 1998). Morphine, which is similar to cocaine in reducing hunger, was extracted from opium in the early 1800s by Friedrich Wilhelm Adam Sertà ¼rner. But its use spread in 1853 when the hypodermic needle was developed (Grilly, 1998). Morphine was used as a pain reliever and as a cure for opium and alcohol addiction. Its extensive use during the American Civil war resulted with people suffering from the soldiers disease (addiction), (Julien et al, 2008). Forms of cocaine The use of crack cocaine, or crack, was first reported in 1980 in Europe and the US as a new drug with rapid stimulating effects. Crack cocaine is a by-product of cocaine, C17H21NO4 (figure 1). However, crack is formed through different processes. First, the coca leaves are transformed into a product known as basic cocaine paste. The paste is then turned into either crack cocaine through chemical treatment with sodium bicarbonate, or into a less potent water soluble salt, cocaine hydrochloride when it is refined with either acetone or sulphuric and hydrochloric acids. The powdered hydrochloride salt can be snorted, and because it is water soluble, it can be injected intravenously (Boghdadi et al., 1997). However, in the hydrochloride form, cocaine decomposes when it is heated and is destroyed to temperature, making it unsuitable for use by inhalation. In contrast, crack cocaine is converted to a stable vapour by heating it (Julien et al., 2008), making it more potent than the concentrated form. The paste and crack cocaine forms can be smoked either on their own or together with tobacco or cannabis-marijuana and sometime mixed with heroin and sold on the street (Goldstein et al., 2009). Cocaine hydrochloride compared to crack cocaine, is less potent and it is used as a local anaesthetic. Its use as anaesthetic first came about in 1884, after Niemann described its anaesthetic properties such as bitter taste and the resultant unusual numbness when applied to the tongue (Goldstein et al., 2009). By the late 1800s, when morphine was already used as a pain reliever, the use of cocaine for its analgesic properties which includes nerve blocking anaesthesia, epidural, and spinal anaesthesia has began to spread (Goldstein et al., 2009). Both cocaine hydrochloride and morphine are still used medically today as anaesthetic, despite their addictive properties. Cocaine hydrochloride is used as a vasoconstricting anaesthetic agent in surgery for ears, nose, and throat (White et al., 2003), while morphine is used as anaesthetic to relieve severe pain. Morphine acts through mu, kappa, and delta opioid receptor to block pain messages to the central and peripheral nervous system (Jul ien et al., 2008), However, morphine produces euphoria by interacting mainly with the mu opioid receptor (rosin et al., 2000). Aim: The aim of this project is to view the complex interaction between cocaine and cocaine receptors and the mechanisms of action of cocaine. Special emphasis will be placed on cocaine tolerance and addiction. To begin with, an overview will be provided on the pharmacokinetics of cocaine by discussing how it is absorbed, distributed, metabolised and excreted. Then, a discussion on how cocaine-induced changes in the peripheral and central nervous system contribute to the euphoric effect and addiction. Finally, an overview of how cocaine dependency could be treated. Pharmacokinetics of cocaine The effect of cocaine on the body depends heavily on the rate of accumulation and the concentration of cocaine at its site of action (the brain) and the duration of contact at these sites (Grilly, 1998). The pharmacokinetics of cocaine refers to its movement in the body with respect to its absorption, distribution, metabolism and excretion from the body and this is dependent on multiple factor such as, route of administration, genetics, and consumption of cocaine (Goldstein et al., 2009). Route of Administration/ Absorption As illustrated in figure two, cocaine is rapidly absorbed from the mucous membranes, the stomach and the lungs. Therefore, cocaine can be snorted, smoked, taken orally, or injected intravenously (Julien et al., 2008). However, the onset and duration of cocaine depends on the method of intake (Grilly, 2006). Cocaine hydrochloride poorly crosses the mucosal membranes when snorted, due to its vasoconstriction properties, thereby constricting blood vessels and limiting its own absorption. Because of the slow absorption of cocaine, its euphoric effect is prolonged when administered intranasally (Boghdadi et al., 1997). Cocaine can be also smoked in the form of crack. Because of its rapid absorption in the pulmonary vascular bed, crack produces an intense high in seconds, peaks at 5 minutes and persists for about 30 minutes. Intravenous injection of cocaine hydrochloride bypasses all the barriers to absorption, placing the total dose of drug immediately into the bloodstream. It produces euphoria in 30-45 seconds (Julien et al., 2008). Distribution After administration, cocaine rapidly penetrates the brain. Initial brain concentrations far exceed the concentration in plasma (Julien et al, 2008). After it penetrates the brain, cocaine is rapidly redistributed to other tissues such as the spleen, kidney, and lungs. Cocaine also binds to plasma protein, albumin and also to ÃŽÂ ±1-acid glycoprotein (Boghdadi et al., 1997). Metabolism Drugs taken orally initially pass through the liver (Figure 2), where they may be metabolised before entering the blood. Cocaine is metabolised primarily into ecgonine methyl ester and benzoylecgonine (Figure 3), the main urinary metabolite of cocaine and can be detected in urine for about 48 hours and up to 2 weeks in chronic users (Butttner et al., 2003). Cocaine is catalysed to ecgonine methyl ester by serum and liver cholinesterases, while benzoylecgonine is hydrolysed non-enzymaticaly (Carrera et al., 2004). Benzoylecgonine have vasoconstrictive properties, however it does not appear to cross the blood-brain barrier readily (Goldstein et al., 2009.). In addition, cocaine is demethylated to formed norcocaine (Figure 3) (Carrera et al., 2004), the only metabolite of cocaine that crosses the blood-brain barrier (Flowler et al., 2001). In the presence of ethanol, cocaine is metabolized to cocaethylene (Buttner et al, 2003). Cocaethylene is as active as cocaine in blocking the presynaptic dopamine reuptake transporter, thereby potentiating the euphoric effect of cocaine, increasing the risk of dual dependency and the severity of withdrawal with chronic patterns of use. This metabolite is more toxic than cocaine and aggravates cocaines toxicity. The half-life of cocaethylene is about 150 minutes, outlasting cocaine in the body (Julien et al., 2008). Even though cocaines plasma half-life is about 50 minutes, several metabolites can be detected by way of urinalysis for up to 2 to 5 days after cocaine overdose (Grilly, 2006). Mechanism of actions of cocaine Cocaines euphoric and reinforcing properties are the result of the obstruction of dopamine transporter (Butterner et al., 2003), thus, increasing dopamine level within the mesolimbic dopamine pathways. The mesolimbic dopamine pathways, shown in figure4, are composed of ventral tegmental area (VTA), the prefrontal cortex (PFC), Hipocampus, amygdale, and the nucleus accumbens (NAc) (Cornish and Kalivas, 2001) (figure 5). The nucleus accumbens (NAc) which consists of two sub-regions, the core and the shell, is believed to be the site for both the primary reinforcing properties of drugs of abuse and conditioned control over drug seeking (Kalivas, 2004). Normally, Dopamine is released into the synapse from an axon terminal in response to a pleasurable signal (Dackis and OBrien, 2001). Once this neurotransmitter is released, it diffuses across the synaptic cleft to bind to their respective receptors, D1 and D2 receptors (Howell* and Kimmel, 2008), which are linked to the cAMP second messengers system via membrane-bound G-proteins. D1family receptors (D1 and D5) are coupled to a stimulatory G-protein (Gs), which when activated increases the production of adenylate cyclase and cAMP and stimulation of the D2 family receptors (D2, D3, and D4) leads to the inhibition of adenylate cyclase through activation of an inhibitory G-protein (Gi/Go) (Cunningham and Kelley, 1993). Dopamine is taking back into the presynaptic neurons through the dopamine transporter, as a result shutting off the signal between neurons by preventing new dopamine to be formed (Howell* and Kimmel, 2008). Cocaine, on the other hand, blocks the dopamine transporter (figure 5), preventing the reuptake of dopamine into the presynaptic neurons of the VTA. Blockade of the transporter augment dopamine level in the synaptic clefts, producing continuous stimulation of dopamine receptors (Anderson and Pierce, 2005). Increasing dopamine concentration in the nucleus accumbens is responsible for the euphoric and reinforcing effects of cocaine. Behavioural sensitisation Repeated cocaine treatment increases dopamine levels in the synaptic cleft, which could lead to further stimulation of the dopamine receptors, causing more intense but shorter behavioural responses (Anderson and Pierce, 2005). This progressive change in behavioural response following repeated cocaine administration is known as behavioural sensitisation or reverse tolerance. The enduring neuronal adaptation in the reward circuit that occur after repeated cocaine administration is believed to be associated with motive and reward (Morgan and Roberts, 2004). The neuroadaptations that result in behavioural sensitization is characterised by two processes, known as initiation and expression (Anderson and Pierce, 2005). Initiation, which takes place in the VTA, is referred to as temporary cellular and molecular changes, such as alteration in various genes, second messenger cascades and receptors densities, which occur in response to psychostimulant administration, while expression is the lon g-lasting neuronal changes that start from the VTA and progress to the nucleus accumbens and striatum to increase behavioural response (Pierce and Kalivas, 1997). It has been reported that repeated cocaine treatment for two weeks increases the sensitivity of dopamine D1 receptors in the olfactory tubercle, nucleus accumbens, ventral pallidum, and substantia nigra and subsensitivity of D2 receptor (Unterwald et al., 1996). Activation of D1 receptors stimulates adenylyl cyclase activity via activation of Gs; increasing sensitivity of D1 and also increased adenylate cyclase and cyclic AMP-dependent protein Kinase (PKA) activity in the nucleus accumbens due to continual activation of Gs protein (Cunningham and Kelley, 1993). However, continuous cocaine treatment decreased D1-like receptor density and function, thereby initiated behavioural tolerance (Keys, and Ellison, 1994). Increased release of dopamine in the nucleus accumbens is also calcium-dependent and relies upon activation of calcium-dependent proteins, calmodulin and calcium-calmodulin kinase II (CaM-KII (Pierce and Kalivas, 1997). It is generally believed that increased calcium conductant and activation of calcium-dependent protein kinase are involved in the release of neurotransmitters in presynaptic nerve terminals and initiation of gene transcription (Evans and Zamponi, 2006). Therefore, continuous activation of calmodulin and CaM-KII by cocaine in the nucleus accumbens may mediate the release of dopamine or other neurotransmitters such as glutamate and GABA that are associated with expression of behavioural sensitisation (Pierce and Kalivas, 1997). D1 receptors located on GABA and glutamate afferents to the VTA are responsible for the release of these neurotransmitters in the nucleus accumbens when activated. Interaction between these neurotransmitters in the VTA changes the regulation of dopamine cell, which initiate long-term neuroadaptations (Cornish and Kalivas, 2001). Glutamatergic systems Excitatory amino acid such as glutamate acts as the main mediators of excitatory signals in the central nervous system (Baler and Volkow, 2006). Glutamate is known to produce its action through ionotropic (NMDA and non-NMDA) and metabotropic (mGluR) subclasses receptors (Danbolt, 1997). Although cocaine does not have a direct influence on brain glutamate systems, repeated exposure to cocaine results in alterations in glutaminergic transmission in the nucleus accumbens (Schmidt et al., 2005). However, the PFC, which transmits major glutaminergic projections to the nucleus accumbens (figure 4) has been most implicated in the regulation of dopamine released from dopamine cell terminals through NMDA and non-NMDA receptors (Kalivas, 1997). It is believed that stimulation of NMDA receptors through a voltage-dependent calcium channel initiate burst firing model in dopamine cells, as a result increasing accumbal dopamine release which is similar to what occurs in behavioural sensitisation (E vans and Zamponi, 2006). Administration of cocaine increases dopamine release presynaptically, which stimulates dopamine D1 receptors, located on descending glutamatergic afferent terminals from the prefrontal cortex (PFC). The D1 receptor in turn, stimulates the release of glutamate in the prefrontal cortex postsynaptic neuron. The released glutamate activates NMDA receptors on the dopaminergic dendrites in this brain area. This sequence of events is augmented by the fact that repeated cocaine administration desensitises dopamine D2 autoreceptors. Desensitisation of D2 receptor reduces the hyper-polarisation of dopamine cells, thereby allowing a further augmentation of dopamine release, which causes supersensitivity of D1 receptors, hence, increasing NMDA activity (Johnson and North, 1992). Because the neuronal circuits are interconnected (figure 5), a reduction in PFC dopamine transmission will activate the nucleus accumbens dopamine release, leading to expression of behavioural sensitisation. Increased glutamate release from the PFC to nucleus accumbens core is associated with cocaine-induced reinstatement and expression of locomotor sensitisation (Torregrossa and Kalivas, 2008). Both Glutamatergic and GABAergic neurons are also joined in the prefrontal cortex, indicating a possible interaction between glutamate and GABA. Therefore, the PFC GABA transmission may also be involved in the development of behavioural sensitisation (Giorgi et al., 2005). GABA systems It has been reported that cocaine sensitisation is linked with a cocaine-induced increased glutamate and GABA levels in the PFC. This was supported by Jayaram and Steketee (2005), who observed an increase in both glutamate and GABA concentration in the prefrontal cortex of animals withdrawn from repeated daily cocaine after the first week following repeated exposure to cocaine, but increase in these neurotransmitters were not observed after prolonged withdrawal. Furthermore, Jayaram and Steketee reported that the AMPA/KA receptor antagonist, (DNQX) prevent cocaine from increase the concentration of GABA in the prefrontal cortex in cocaine-sensitised animals. Therefore, increasing the response of GABAergic neurons in the PFC is a consequence of enhance glutamate level in prefrontal cortex. Because the AMPA/KA receptor antagonists seem to block cocaine from augmenting GABA levels, it can be concluded that glutamate acts mainly through AMPA/KA receptors to increase GABAergic activity in the prefrontal cortex. However, decrease in GABAÃŽÂ ² receptors function in the PFC is also associated with sensitisation of locomotors. It is believed that a loss in GABAÃŽÂ ² function in the prefrontal cortex would lead to a decrease in inhibitory modulation of excitatory pyramidal output neurons in the PFC (Badran et al., 1997), and therefore, a simultaneous increase in glutamatergic transmission in subcortical regions associated with the expression of behavioural sensitisation (McFarland et al., 2003). Glutamatergic, GABAergic and midbrain dopamine neurons are joined onto dendritic spines of medium spiny neurons that contain GABA, and endogenous opioid peptides. These opioid-containing neurons project directly to the substantia nigra and VTA to synapse on dopamine cells (Yung and Bolam, 2000). Therefore, alteration of endogenous opioid may participate in the development of drug abuse. Opioid systems It has been suggested that dopamine and opioid act together to modulate locomotion, mood and motivated behavioural, therefore, modification of the endogenous opioids participate in the development of drug of abuse. In addition the opioid system could also influence drug craving and relapse by altering stress physiology (Rosin et al. 2000). Apart from dopaminergic system, the endogenous opioid system is also a major player in addiction. Opioid system consists of three G-protein coupled receptors, termed mu (ÃŽÂ ¼), kappa (ÃŽÂ º), and delta (ÃŽÂ ´) opioid receptors. They act through G-protein second messenger systems (Go/Gi) to inhibit adenylate cyclase and cyclic AMP (Contet et al., 2004). Activation of these receptors on presynaptic axon terminals inhibits the Ca2+ influx that underlies release of neurotransmitters (Evans and Zamponi, 2006). At the postsynaptic membrane, their activation hyperpolarises the membranes by enhancing K+ flow out of neurons (Taddese et al., 1995) mu ( µ)-opioid receptor Mu ( µ) opioid receptors mediate positive reinforcement following direct morphine or indirect alcohol, cannabinoids and nicotine activation (Jullien et al, 2008). The positive reinforcing and euphoric effect of morphine involved dopaminergic as well as mu opioid receptors. Morphine activates ÃŽÂ ¼-opioid receptors through inhibitory Go/Gi protein, which decreases the level of adenylate cyclase and the cAMP pathways in the VTA (Contet et al, 2004). Because opioid and GABA containing-neurons also project in the VTA, activation of  µ receptor inhibits the release of GABA on dopamine, leading to high level of dopamine in the nucleus accumbens and other area. The increase in dopamine level in the nucleus accumbens leads to the positive reinforcement of opioid addiction (Bartoletti et al., 1999), which is also related to cocaine reinforcing effect (Julien et al., 2008). Stimulation of  µ opioid receptor in the VP is thought to promote motor activity, in part, by red ucing presynaptic release of GABA (Torregrossa and Kalivas, 2008). Repeated cocaine administration results in reduced extracellular GABA in the VP due to increasing stimulation of presynaptic  µ opioid receptors (Tang, et al. 2005). 2. K-opioid receptors ÃŽÅ ¡-opioid receptor system is essential in regulating presynaptic dopamine release and administration of dynorphin (DYN) within the nucleus accumbens (Shippenberg and Rea, 1997). DYN, endogenous ligand for the ÃŽÂ º-opioid receptor prevents the sensitisation that develops to locomotor stimulatory and conditioned reinforcing effect of cocaine. Anatomical studies have shown interaction between the mesolimbic dopamine neurons and neurons containing the opioid peptide dynorphin (Yung and Bolam, 2000. As mentioned above, dynorphin are found in dentritic spine of medium spiny neurons and project to the VTA and nucleus accumbens in which ÃŽÂ º-opioid receptors are expressed. However, the accumbens shell express high density of ÃŽÂ º-opioid receptors (Jayaram and Steketee,). Microdialysis studies have shown that the systemic administration of selective ÃŽÂ º-opioid receptor agonists such as U50488 and U69593 depress the firing rate of mesolimbic dopamine neurons and decreases dopamine overflow in the nucleus accumbens (Shippenberg and Rea, 1997). Therefore, activation of ÃŽÂ º-opioid receptor will inhibit dopamine release in the nucleus accumbens. However, Kuzmin et al., 1997 showed that acute administration of selective ÃŽÂ º-opioid receptor antagonist, nor-binaltorphimine increases dopamine overflow within the nucleus accumbens. In addition to these findings, it is believed that dopamine D1 or D2 receptor agonist, apomorphine, increases dynophin immunoreactivity and prodynorphin mRNA in the nucleus (Li et al., 1990). Therefore, repeated administration of cocaine increases prodynorphin mRNA in the nucleus accumbens and striatum. Taken in to account all these findings, and the role of ÃŽÂ º-opioid receptors in presynaptic modulation of dopamine release, it can be concluded that an increase in the extracellular level of dopamine within the nucleus accumbens results in a compensatory increase in the activity of dynorphinergic neurons. However, this increase is insufficient to prevent the development of behavioural sensitisation. Because many of the above intracellular adaptation involve changes in protein levels, it can be though that regulation of gene expression may be involved in the long-lasting effects of cocaine. Cocaine regulates gene expression It has been reported that one of the early molecular events following cocaine administration is the activation of nuclear protein (CREB) (Konradi et al., 1994). CREB control the changing that occur in synaptic neurons through modulation of the expression of several cAMP-inducible genes. CREB is regulated via phosphorylation at serine-133 (Konradi et al., 1994) The kinase inducible domain (KID) that contains serine-133 amino acid residue is phosphorylated by cAMP-dependent protein kinase A (PKA), and Ca2+/calmodulin-dependent protein kinases II and IV (CaMK II and IV) (Lonze and Ginty, 2002). Phosphorylation of CREB by PKA and CaMK II and IV results in the expression of immediate early genes (IEGs) including Fos and Jun, which are members of the transcription factor activator protein-1 (AP-1) family (Soderling, 1999). Acute cocaine administration activates DNA-binding activity of the AP-1 and expression c-Fos, FosB and JunB proteins (Hope et al., 1992). Chronic cocaine exposure is believed to reduce the capability of cocaine to express c-Fos, JunB and FosB proteins. This results in prolonged accumulation of à ¢Ã‹â€ Ã¢â‚¬  FosB proteins (a shorter splice-variant of FosB), which produces more persistent AP-1 complex (Hiroi et al., 1997). Prolonged accumulation of à ¢Ã‹â€ Ã¢â‚¬  FosB was reported in a variety of knockout and transgenic mice studies. Hiroi et al (1997) showed that mice lacking Fos-B and its shorter splice- variant à ¢Ã‹â€ Ã¢â‚¬  Fos-B had reduced AP-1 complexes following chronic cocaine exposure and increases cocaine-mediated hyper-locomotion and conditioned place (CPP) preference. They also observed that the long-term over expression of à ¢Ã‹â€ Ã¢â‚¬  Fos-B increases AP-1 complexes and behavioural sensitisation in both the nucleus accumbens and striatum. Increased neuronal expression of Fos in these regions after cocaine treatment is mediated by increasing D1 dopamine receptor activation, due to high level of extracellular dopamine. Desensitisation Chronic cocaine administration repeatedly stimulates dopamine receptors, as a result, decreases the concentration of dopamine within mesolimbic system and the remaining receptors become less sensitive to dopamine. Decrease in dopamine concentration leads to tolerance. This has been reported in several studies. For example, Maisonneuve et al (1995) observed a reduction in the basal dopamine concentration of rats nucleus accumbens when 10 or 15 mg/kg of cocaine was administered three times every day per hour for 13 days. Additionally, Inada et al (1992) showed that repeated cocaine administration in rats, reduced dopamine response to cocaine striatum 24 h after withdrawal. Decrease in dopaminergic level also leads to behavioural tolerance. Tolerance Tolerance refers to a decrease in response to cocaine due to repeated exposure of the drug (Maisonneuve et al., 1995). The major contributory factor to tolerance is the supersensitivity of D2-like autoreceptors as a result of D1 receptors desensitisation after chronic cocaine treatment (King et al., 1994). King et al showed that following chronic administration of 40 mg/kg of cocaine per day, for 7 days, increases sensitivity of D2-1ike receptors in the nucleus accumbens. Increasing D2 receptors leads to a transient decrease in the levels of GiÃŽÂ ± and GoÃŽÂ ± proteins linked to these receptors (King et al., 1994). Continuous cocaine administration produces tolerance to the inhibitory effects of cocaine on dopamine uptake in striatum and nucleus accumbens. Therefore, blockade of dopamine uptake by cocaine produces a compensatory increase of dopamine reuptake transporters (Letchworth et al, 2001). However, repeated cocaine treatment decreases the mRNA expression of dopamine transporter in the VTA neurons that project to the limbic brain regions during withdraw (Hammer et al., 1997). Polymorphism in the genes of dopamine transporter (DAT1) and receptors could be implicated in the genetic susceptibility to the complications of long-term development use in different individual (Wang et al., 2004). There are two main types of DAT1 genes, the SLC6A3 gene and the 3 untranslated VNTR polymorphism. The SLC6A3 is localised to chromosome 5p15.3 and genetic variation in SLC6A3 are thought to change the expression of DAT1 (Fuke et al., 2001). The variable number tandem repeat (VNTR) polymorphism in the 3untranslated region of DAT1 consists of a 40-bp repetitive sequence and can vary from 3 to 12 repeats. However the two most common alleles are the 9-repeat and the 10-repeat, and several studies have linked these polymorphisms to prolonged psychosis following stimulant withdrawal. Fuke et al (2001) reported that the 10-repeat allele (10R) enhances the expression of the DAT1 protein, while Michelhaugh et al (2001) claimed that the 9-repeat allele (9R) enhanced the DAT1 expression. However both studies found that the DAT1 VNTR is associated with drug addictions. The gene for D2 dopamine receptor (DRD2), TaqI A (rs1800497) is a single-nucleotide polymorphism (SNP) with two variant; A1, the less frequent allele, and A2, the commoner allele. Accumulative evidence from post-mortem brain samples using a [3H] binding ligand and in living subjects using positron emission tomography (PET) showed that the presence of the A1 allele leads to a decrease in D2 dopamine receptor density, as a consequence of chronic cocaine treatment (Thompson et al. 1997). Therefore, the DRD2 A1 allele is implicated in addictive behaviours. Several studies on different populations suggested that the involvement of TaqI A and VNT

Bats :: essays research papers

Bats Contents 1. Title Page Page... 1 2.  Ã‚  Ã‚  Ã‚  Ã‚  Contents  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Page... 2 3.  Ã‚  Ã‚  Ã‚  Ã‚  Bat Facts Page... 3-4 4.  Ã‚  Ã‚  Ã‚  Ã‚  Congress Ave. Bridge Page... 5-6 5.  Ã‚  Ã‚  Ã‚  Ã‚  How To Get A Bat Out Of Your House Page... 6 6.  Ã‚  Ã‚  Ã‚  Ã‚  About Bat Houses  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Page... 7 7.  Ã‚  Ã‚  Ã‚  Ã‚  References  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Page... 8+   Ã‚  Ã‚  Ã‚  Ã‚  My report is on bats. I will start my story off by telling you some facts about bats. Bat Facts 1. Did you know that the worlds smallest mammal is a Bumblebee bat that lives in Thailand. It weighs less than a penny! 2. Vampire bats adopt orphan pups (the name for a baby bat) and have been known to risk their lives to share food with the less fortunate. 3. The African Heart-Nosed bat can hear the footsteps of a beetle walking on sand from a distance of over six feet! 4. The giant Flying Fox bat from Indonesia has a wing span of six feet! 5. Disk-winged bats of Latin America have adhesive disks on both feet that enable them to live in unfurling banana leaves (or even walk up a window pane). 6. Nearly 1,000 kinds of bats account for almost a quarter of all mammal species, and most are highly beneficial. 7. Worldwide, bats are the most important natural enemies of night- flying insects! 8. A single brown bat can catch over 600 mosquitoes in just one hour! 9. Tropical bats are key elements in rain forest ecosystems which rely on them to pollinate flowers and disperse seeds for countless trees and shrubs. 10. Bat droppings in caves support whole ecosystems of unique organisms, including bacteria useful in detoxifying wastes, improving detergents, and producing gasohol and antibiotics. 11. More than 50% of American bat species are in severe decline or already listed as endangered. Losses are occurring at alarming rates worldwide. 12. All mammals can contract rabies; however, even the less than half of one percent of bats that do, normally bite only in self- defense and pose little threat to people who do not handle them. 13. An anticoagulant from Vampire bat saliva may soon be used to treat human heart patients. 14. Contrary to popular misconception, bats are not blind, do not become entangled in human hair, and seldom transmit disease to other animals or humans.   Ã‚  Ã‚  Ã‚  Ã‚  Well, enough with the facts. I think that should get you ready for the rest of my essay.   Ã‚  Ã‚  Ã‚  Ã‚  Austin, Texas Congress Ave. Bridge   Ã‚  Ã‚  Ã‚  Ã‚  A Bit Of History.......   Ã‚  Ã‚  Ã‚  Ã‚  When Engineers reconstructed downtown Austin's Congress Bridge in 1980, they had no idea that the new crevices beneath the bridge would make an ideal bat roost. Although bats had lived in Austin for years, it was headline news when they suddenly began moving by the thousands under the bridge.