Java Technology Essay Example | Topics and Well Written Essays - 750 words

Java Technology - Essay Example Sun systems first released the language to the public in 1995, with a promise of portability to run anywhere without many modifications. From this instance, Java quickly developed and was incorporated into many web browsers. The main goal of the developers was a language that was high performing, dynamic, threaded, robust, secure, and neutral in architecture, simple, familiar and object oriented. Various existing types of Java today have been developed with time since the language was developed. They include; JDK (1.0 and 1.1), J2SE (1.2, 1.3, 1.4 and 5.0), Java SE (6, 7 and 8). Due to the diversity in functionality and the sense of portability that has allowed the language to be put into practice in most Operating Systems developers, the language is now incorporated into almost all systems. Due to the presence of the Java virtual machine, the language is currently the most applicable for development of most web-based software as it allows independence in platform usage (portability). Being a high-level language, Java is used to make applications that can store data, transmit information, play games, develop android applications and do a myriad of other things. The major concept of Java is "Object oriented Programming." It is, therefore, necessary to learn the concepts of OOP in order to learn Java more easily. Above the OOP concepts, learning C or C++ would make one learn Java easily, considering that the language was developed from these languages. The de facto standard for Java implementation today is Oracle Corporation, which is the current owner of Sun Microsystems. This implementation has been widely accepted across various platforms such as Windows, Linux, Mac and Solaris. The implementation, which is mainly based on the Java SE platform. contains a "Java Runtime Environment" for end users and a "Java Development Kit for developers." There was an initial problem with the compiler that made programs developed in this language to run slower than

Options And Corporate Finance Essay Example for Free

Options And Corporate Finance Essay In a perfect world, the stock price will drop by the amount of the â€Å"special one- time† dividend on the ex-dividend date. If we ignore taxes as we do in this mini- case the wealth of the shareholders doesn’t change if the company pays a special one-time dividend or not because it is reflected in the stock price. As we also saw in class that a dividend policy for a company is irrelevant since investors can convert share to cash or create their own homemade dividends payments if they prefer an income stream. In essence, paying the dividend is transferring money from the company to the shareholders but net the wealth of the shareholder stay the same due to a similar drop in the share price, but the value of the company will decrease. 2. The proposal of Jessica could go both ways, it could increase the value of the company or decrease the value, for the simple reason that we don’t have any information about leverage, the amount of debt, capital structure etc. If the company is overleveraged that will result in extra costs of financial distress, which consist of direct, indirect and agency costs. An overleveraged company goes past the optimal point and will decrease in value as you can see from the red line. If this is the case then it would be a good idea to reduce the amount of debt which results in a reduction of costs related to financial distress and invest the money in new facilities to increase the overall value of the company. If the company didn’t reach it equilibrium point than it would be a bad idea to reduce the amount of debt because it will decrease the value of the company due to the tax advantages (tax shield), so it would be better to keep the amount of debt to and maybe even increase the debt to reach the maximum company value. This are two options which can increase or decrease the value of the company. Another point could be that we don’t know about future prospect of the current technology and if there is enough demand, and if they now use their full production capacity. If not the case then it would be a bad idea to upgrade and expand, but it would be better to invest in research for new technology. 3. Nolan is correct in the sense that all three indicators will increase due to share repurchase. It will increase the P/E ratio because there are less shares available and it will reduce the denominator of both ROA and ROE which will result in an increase in both ratios. However, a share repurchase will not have any effect on the value of the company for the reasons we discussed in question 1, which is that the dividend policy is irrelevant to the value of the company and it won’t have any effect on the wealth of shareholders. 4. When a company starts with a dividend policy it gives a signal to the shareholders/investors that they are committed to distribute part of their income to their shareholders. If they would start with regular dividend payments they should be sure that they are able to continue that forever, because a reduction in dividend or if they stop paying dividend at all at a later stage will send a negative signal to the market and shareholders/investors. So, they need to make sure that they have enough cash to keep the dividend policy going. To come back to the question, I would evaluate it regarding the company’s ability to pay the dividend for an infinite time period and I they will have enough cash in the future or generate enough cash in the future to pay the dividends. 5. If the company wants to expand (and it is able to do so) the trade-off is lower dividends to their shareholders than when they are a mature company who has no growth potential than they would pay dividend. The implications of the formula are that the company should make a trade-off/decision between company growth or pay the dividend to its shareholders. To please its shareholders and to maximize the company’s value, the company should deliver the required rate of return which is wanted by the shareholders or deliver a higher return to make the shareholders happy. If the company can have a higher rate of return than wanted by the shareholders it should retain earnings to invest in the growth to increase the rate of return, when this is not possible it should pay the shareholders their dividend to give them their required rate of return. But if the company retain its earnings when the rate of return is lower than wanted by the shareholders it lowers the company’s value .

Robinson Jeffers Essay -- essays research papers

The Nature of Man by Robinson Jeffers Robinson Jeffers is one of the twentieth centuries most important and controversial poets. He, like others in history, has tried to give his opinion about life. Many poets in the twentieth century focused on issues affecting mankind, Jeffers is no exception. Most of his work was inspired by his surroundings. One’s environment is great source for poetic inspiration. Poets come and go, but their ideas are kept alive through their poems. Whether they are a hundred or ten years old, these poems hold ideas in them which are still interesting now as they were back then. It seems that poets are always passionate about their work. They should be, since it expresses who they are and what they believe in through writing. One tends to write about what one knows or feels one might know. Feelings control our mind and our mind controls our actions. How we feel can be determined by external forces. Sometimes, one lets emotions run wild which can cause our work to be accepted or rejected by o thers.   Ã‚  Ã‚  Ã‚  Ã‚  One must not worry about writing something which might cause a brush off by society. However, writings such as these can create a cold shoulder for one’s future work. Then again, poetry is used to express oneself. Society will only encourage radical behavior to continue and who knows, one’s ideas might generate a fan base. A poet cannot please everyone. There are some emotions which will be seen as pleasant ideas and some which will seem disrespectful. Poetry, that is controversial, seems to captivate an audience and it accomplishes one’s lofty goals. One’s courageous work commands respect, whether the reader agrees with the ideas or not. Poems are intended to force the audience to see one’s views. Though the reader’s views often contradict your own, the most important part is to make them consider new ideas and better understand the issues. Although, many of issues will never be understood.   Ã‚  Ã‚  Ã‚  Ã‚  Poets often tend to write openly about this. Man is involved with everything in this world. Mankind as a whole has progressed in knowledge and technology. In other areas, on the other hand, it has stayed the same or has gotten worst. Poets for centuries have written about man. Few, have written using facts. Yet more have written using their opinions. Thousands of books have been written about... ...rica’s intervention. â€Å"The squid, frightened and angry, shoots darkness out of her ink sac; the fighting destroyer throws out a smoke screen, and fighting governments produce lies.† Jeffers kept pushing his views of man stating that our race began to think as an adult does, rather than an egocentric baby. He also believed that man controlled the keys of unearthly violence. Claiming that Earth is too small to feed us and we must have room. Also, Jeffers was once quoted saying, â€Å"We use to be individuals, not populations. Breeding like rabbits, we hasten to meet the day.†(Birth and Death) In later poems, he began to wonder what was the best life for a man. Jeffers came to the conclusion that man should have never been born and the next best was to die young. (The Silent Shepherd) As his reputation fell, Jeffers began less on man. Jeffers expressed his contempt for human society, which he regarded as doomed by its own violence and depravity. With his unc ompromising reverence for nonhuman values and his World War II isolationism, Jeffers fell out of favor with the public. Even though still outspoken after the war, newly created patriotism in America did nothing but anger many Americans.

Promote Positive Outcomes with Children and Young People Essay

The social factors that can affect the way in which a child or young person develop are firstly peoples views within society especially for disabled people they are pre judges and discriminated against because of their disability because of this they are being marginalised from society and excluded from such things like social events. Young person that are in the care system can be affected as they are not having consistency within their life at any one time. Other social factors can be poor social skills such as bad reading or writing especially if these skills are not identified as young person needing help young person will not develop to their full potential. attitudes to others is a social skill that can affect young person achieving this can be a result of other family members with disability or for young person who have come from bad backgrounds i. e domestic violence or drug use. Economic factors that could affect the way in which young person and young people develop is poverty, many families who have good stable homes are suffering with the economy and it is hard for people to lead healthy life’s and afford good housing accommodation, healthy foods and good health. Other factors could be injustice. Cultural factors that affect young people and young person could be the attitude of their parents this is not always the case but in some families with strong religious beliefs it is hard for them to do things outside the family home. This can result in lack of social development. Disability can impact on the life of a child firstly because of discrimination. within society young person get discrimianted against because there disability this could be by not been included within groups of young person because of their disability. this happens often in society because young people or young person do not understand what disability is at a young age. The result of this discrimination happening could be that the child or young erson could get depressed and have low self esteem, from not been included. The lack of oppurtunites avaliable for disabled people could effect disabled or young peoples lifes this could be no disabled access which acts as a barrier for the disabled people when they are trying to lead normal lifes. When disabled people cant use public facilities as mentioned above it also gives them a barrier to choice and they cant choose to do things which are not avaliable for them. ositive attitududes to young young person are important with disabilities it shows that they are focusing primaraliary on the child as a human being and by them not being disabled. this impacts on the disabled person leading a normal life as possible and minimises the effect of their disability. Praising young people is a good way to build up their confidance and sefl-asteem no matter how big or small their achevements are. eople with learing difficulties can also prevent them being fully independent as they will always need some kind of help and support whether that be with money or decision making. this could result in a lake of job oppurtunities in the future Eqaulity means that everyone is treated equally. By treating young person equally they can achieve the every child matters five outcomes which are stay safe, enjoy and achieve, be healthy, make a positive contribution and echieve economic well bieng. We are alos promoting the individuals rigths by treating individuals equal. we must respect the childs choices and fairness. and we must respond to their choices in following what they wish to do and responding to their needs. We can promote equality within the workplace by following policies and procedures, challenging discrimination that happens by following procedures, improving participation for example including young people in activities outside the home and school example youth/sports clubs. romoting digintiy and respect can promote equality and invloving the young people in their own planning and delivery of services for example person centred planning – doing activities the child wishes to do. Diversity means that all young person must mix together no matter what their culture is. within our home young person are all diverse and all come from different backgrounds and religion we must respect individuals no matter what they belive. othere examples of being diverse are, culture nationality, ability, ethnic orogin, gender age, beliefs, sexual orienation and social class. Ee can support diversity by valuing these differences and acting on and promoting them within the workplace. Our young people do learn about different back grounds and cultures during education and have done themed lunches. Also my key child is christian as are his family he chooses not to go to church however since the loss of his mum he does go to the catherderal on special occasions i. e. Mum’s birthday, Christmas and he will light a candel for his mum.

Second Periodic Test

PERIODIC EXAM ENGLISH Name: _________________________________Year & Section: _________________________ I. SPEAKING: DIRECTIONS: Tell whether the statements below use a RISING INTONATION or a RISING- FALLING INTONATION. Write R for rising and RF for rising-falling intonation. _____1. Have you study your lessons? _____2. I have seen the movie twice. _____3. When is the deadline for the submission of our project? _____4. Are you sure? _____5. She might be late. II. READING & LITERATURE A. DIRECTIONS: Use the articles A, AN and THE in the nouns below: 6.The leader of ___________ group is good. 7. _______ apple a day keeps the doctor away. 8. My father is ________ honorable man. 9. We went to _________ DILG office. 10. ______ new song is being played. B. DIRECTIONS: Select the reference material needed below. Write your answer on the space provided. _________________________11. The population of the Philippines in 1990. _________________________12. The meaning of the word â€Å"outrageou s†. _________________________13. The different kinds of insects. _________________________14. The color of the Japanese flag. ________________________15. The stress mark of the word â€Å"sedimentary. † ( YEARBOOK OR ALMANAC, ENCYCLOPEDIA, ATLAS, DICTIONARY ) C. DIRECTIONG: Supply the missing word in the analogy below: 16. School is to study as church is to ______________________. 17. Bark is to dog as buzz is to _______________________. 18. White is to good as black is to ___________________. 19. Sun is to day as moon is to ____________________. 20. Allah is to Muslim as Christ is to ___________________. D. DIRECTIONS: Encircle the letter of the correct answer. 21.Who is the wife of Leon? a. Mariab. Emeliac. Lumnay 22. What did Mr. Angeles brought to his family? a. caretelab. beansc. mats 23. The following are dead children of Mr. Angeles EXCEPT†¦ a. Josefinab. Marcelinac. Victoria 24. He was the brother of Leon. a. Juanb. Antonioc. Baldo 25. She was the new wife of Awiyao. a. Madulimayb. Madulumnayc. Lumnay E. DIRECTIONS: TRUE OR FALSE. WriteT if the statement is true and F if it is wrong. ___26. Maria was afraid of Labang. ___27. The beads given to Lumnay by Awiyao will be given to Madulimay in the wedding. __28. All the children of Mr. Angeles have received a mat. ___29. Marcelina’s mat has a symbol of Aesculapius for she is a medical student. ___30. The passing at night at the Waig was one of the tests given by Leon’s father to Maria. ___31. Maria was a typical city woman. ___32. Maria was not accepted by the family of Leon. ___33. The mats brought by Mr. Angeles were special and unique. ___34. The reason of the separation of Awiyao and Lumnay was Madulimay. ___35. Lumnay joins in the wedding dance and finds also a husband. III. GRAMMAR A.DIRECTIONS: Identify the pattern of the sentences below. Write S-TV-DO or S-TV-IO-DO in the space provided. _________________36. Mr. Angeles gave Nanay Emilia a mat. _________________37. A wiyao left Lumnay. _________________38. Leon showed Maria the place. _________________39. Mr. Angeles brought presents. _________________40. Awiyao comforted Lumnay. _________________41. Mr. Angeles remembered his dead children. _________________42. Leon’s family accepted Maria. _________________43. Awiyao gave her the beads. _________________44. Lumnay offered Kabunian a pig. ________________45. Awiyao asked Lumnay a question. B. DIRECTIONS: Look for the prepositions in the poem below. Encircle a preposition only once. A thousand times in my dreams I have walked with you Hand in hand, down the glittery way Without a worry, not a care in the world, No sorrow, no torture, no dismay, There we were: two figures in the incessant night, Swallowed by the searing darkness Embraced by the fleeting sadness, And then we would look to the sky and see, The shining harvest of the distant stars, Our sky, our sky, my starlight, our sky sown with stars.

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buy custom Employment Law essay Employment law also referred to as labor law governs the relationship between an employer and employee or unions and employers. It usually states the rights of the employee embedded in the employment contract. Employment law is integral in social and economic development in any country. It is instrumental in determining the wage, working hours, benefits, safety and health, anti-discrimination and employment termination conditions. Employment Contract The similarity of the employment contract in any country is that it states rights and obligations of the worker and the employer. At the time of hiring, the employee should be provided with a written document of the essential terms, of which he must give consent. The contract states the minimum wage that the worker will be paid per hour. The worker will consent to the wages if they are enough for him. Minimum wages vary from one country to another and also from one job to another (Courtney 2007). The employers cannot pay the employees a wage less than the minimum wage in a country, but he can pay him an amount more than it according to the tasks performed at the work place. Minimum wage laws are usually a result of bargaining between the unions and employers and are usually at par with the economic development and living costs in a country. Another issue governed by the employment contract; is working hours. The terms and conditions of the contract will state the working hours of the employee. In the modern world, where different issues require the attention of the employee some organizations have embraced flextime. Flextime is that the employee can work at times he is comfortable. The working hours will be stated, and other issues like overtime addressed in the employment contract. The employee will be paid for all the overtime he works. During the industrial revolution days, working days had about 16-15 hours a day. Legislation has reduced it to 14 hours and today the working day is normally between 8 to 9 hours a day. After the normal working hours are finished, the extra hours worked by the employee are considered overtime and the employer must compensate him accordingly. It also governs the health and safety of the worker at the working place. The employer should make the working place as safe as possible. The act states the standards to which the employer must adhere to ensuring the safety of the worker. Employeesalso have a right to be insured against harm to him in the course of work. The factory safety act requires employers to make the working environment as safe as possible. He should also ensure proper ventilation, proper fire exits and fire fighting equipments, clean environment and access to facilities at the work place. Various legislations to ensure proper health of the workers, and safetyin theirwork places such as in mines and the general work environment have been initiated to protect the worker. It also states the leaves from work that the employee will have. The contract states the number of times the employee can access the leaves in a year. The worker may take a maternity leave of which will last for the time agreed with the employer. Other workers may access the leaves once or twice a year as embedded in the employment contract. The types of leaves the employee may access include paternity leave, annual leave, sick leave and public holidays of the country. The worker may be given full pay during the leave or paid according to the agreed conditions. Maternity leave to the worker is also an issue in the employment law. The period and number of times the worker can access this leave is set by the employer. Racial or sexist discrimination policies are addressed in the employment contract. Discrimination of any sort is illegal at the work place. It is also morally unacceptable to subject employees to discrimination of any kind. In the terms and conditions of the employment contract, the employee must be assured of a discrimination free working environment. Mechanisms should be put in place to ensure those in authority do not discriminate against the employees, either racially or through sexual orientation. Promotion and allocation of tasks should be allocated fairly to ensure the satisfaction of every worker. Other issues addressed in the employment contract include contract termination conditions. It states the procedure for laying off workers. Employees should be paid severance pay for a stated number of days after termination of his contract. Termination may be due to completion of the contract or laying off by the firm to meet its objectives of cutting costs or any other objective. The ease with which an employer can fire and hire employees is determined by the employment contract. Other issues addressed is child labour, right of workers to join trade unions, join strikes and boycotts, workplaace involvement and other issues relating to the employee and employer relationship. It also governs the behavior of the employee in the course of his work. He must perform his work to a standard required to the employer. Employers are not allowed to hire people under the age of 18. They should also grant employees the right to join unions and sometimes allow them join strikes. The duties of the employee should be clearly stated to avoid conflicts at the work place. The types of employment contracts are the permanent employment contract and the fixed term employment contract. They are similar only that the fixed term employment contract states the starting date and ending date of the contract. They may choose to renew the contract or not. The other features are similar in that the employer offers the prospective employee the contract, and he signs it if the terms and conditions are favorable to him. Permanent employment contract can only be terminated if the worker does not suit the needs of the business anymore, or the firm wants to cut costs or any other reason. The worker has the right to severance pay for a number of days that differ from one country to another. Since the industrial revolution, various legislative authorities have attempted to streamline the sector. Various acts touching on issues as employee safety and health, working hours, child labor, minimum wages and other labor issues have been put in place. One such act is the employment rights act of 1996 in the United Kingdom and the New Zealand employment relations act 2000. Every country strives to regulate the relationship between the worker and the employer by using the legislative tools. From time to time legislation is needed to govern the terms between the employer and employee as circumstances keep on changing. In relation to these changes in circumstances and situation, the legislative bodies should devise strategies to keep the employment laws up to date. Conclusion The employment contract is an important document governing the relationship between the employee and employer. It determines the input of the worker at work while ensuring him a safe working environment. Employment law in any country is crucial as it governs the interests of both parties, who are, the worker and employer. Continuous revision on the employment terms and conditions should be done to ensure it is up to date to economic conditions in a country. Buy custom Employment Law essay

Colgate Hinterland Marketing in India Essays

Colgate Hinterland Marketing in India Essays Colgate Hinterland Marketing in India Essay Colgate Hinterland Marketing in India Essay Oral hygiene in the hinterlands Colgate Colgate. The world’s most recognizable oral care brand, it belongs to the Colgate-Palmolive Company. Colgate was the first toothpaste in a collapsible tube, introduced in 1896. It is a worldwide household name and synonymous with the product itself in various regions. Colgate-Palmolive has its presence in about 200 countries. Colgate in India Present in India since the 1930s, Colgate is almost synonymous with toothpaste in the Indian market. It is accepted well both in the rural and urban areas. It has been ranked as the 17th most trusted brand in India by The Brand Trust Report.Brand and Market Share Colgate is the market leader in oral care business in India, and by some distance. Colgate leads the sector with a whopping 53% market share. HUL, who sell under the brand name Pepsodent’, is a distant second with 22%. The other major player in the market is Dabur. Going to the hinterlands The rural market Having taken the urban market, the rural market was the next logical destination for Colgate. Yet, it was not just logical but a potentially rewarding one too. Over 70% of India lived in villages and oral dental care products were yet to reach there.If there ever was a latent market, this was it. As with every reward, the rural market posed its challenges too. * Many people in India still used traditional products like neem twig, salt, ash, tobacco and herbal products. * The red and black toothpowder still accounted for 35% of the tooth powder market. * The rural audience was heavily scattered. India’s diversity resided in its villages: Innumerable cultures, subcultures, languages, dialects, etc. * The awareness on oral health products was very low. * Most of rural India was media-dark. Traditional media did not reach many of India’s villages. StrategyColgate’s rural promotional and advertising program was launched under the name of Sampark’ meaning Communication’. Sampark had three main objectives: 1. Explore presence of media at different levels: It focused on identifying and making use of pre-existing media and promotional machinery that was prevalent in localized rural parts of India, viz. , Weekly bazaars, Haats, Jatras, Festivals, etc. 2. Assess characteristics of the rural market by collecting region-specific consumer profiles Analyze the different consumer profiles that existed in rural markets pertaining to age, social status, financial capability, beliefs and preferences.Example: a) Older Generation: Misri user (traditional ground tobacco) b) Middle Aged: Tooth powder user c) Younger generation: Toothpaste user 3. To design, communicate, motivate the audience to buy the product Sampark had limited budget at its disposal. Going in for mass media would not prove to be costly but the reach would be limited as, still only very few people owned possessed a TV or a radio. i) Door to door selling: Sampark wanted something that had far wide reach. Hence, Colgate chose door to door selling. ii) Right people for the right job: Sampark hired people locally who knew the local language, jargons idioms.This not only helped Colgate communicate easily with the consumer but was also effective in sending the right message across to the rural consumer. These people would move about in the villages telling people about the pros of using advanced oral care products the cons involved in using traditional oral care products. This was quite difficult as rural people felt that natural products were the best. iii) Training the Salesmen: Colgate trained salesmen to convince the rural population and make them try samples that Colgate was distributing free. v) AV vans: The next best option that Sampark choose after door to door selling was publicity vans, also called A/V vans. Seventy promotional vans did the rounds of the country educated rural folks on oral hygiene products such as toothpaste, toothpowder toothbrushes. These vans used to travel from village to village depending upon the day of the weekly market in that specific village. These vans also did a number of other activities at a time such as spot selling, sampling and retailing. The vans used to be parked in strategic locations. They were highly decorated so as to get more eyes turned in the process educate the rural folk.The roving Colgate vans, after screening a 22 minute film on oral hygiene that explained how to use the product, offered sampling at stalls setup near the van. 60% of the towns were covered by Colgate with their own distribution channels. The remaining 40 percent was covered by other distributors. v) Puppet shows: There were puppet shows done in the villages educating the villagers about the plus points of using modern oral hygiene products. vi) Educational films: Educational films were also shown in between movies in theatres. These were usually 10-40 seconds long.They feature either actors, local lenders or a farmer that was like one of them. Later on, after the movie ended free samples were distributed to the audience. These tactics were also used in Haats Melas throughout the length breadth of the country. vii) Teacher training programmes: It was an integral part of the School Dental Health Program, conducted regularly across the country to promote preventive dental health care. viii) Oral health educational programme: The Colgate Rural Initiative was targeted at rural areas of population between thirty and hundred thousand.The dental checkup camps were supervised by dentists. The organizers interacted with over 1 lakh people teaching them the benefits of oral hygiene. Conclusion: Post the saturation of its urban market, Colgate had to find new markets. Rural market was the logical next step. Finding that usual promotional and distributional channels shall not work in rural India, Colgate explored niche rural channels to raise awareness on both oral hygiene and the product. Colgate’s ultimate success bears testimony to their strategy which stands as a guiding lesson in approaching newer markets.

8 Striking Ideas to Get out of Professional Essay Samples

8 Striking Ideas to Get out of Professional Essay Samples 8 Striking Ideas to Get out of Professional Essay Samples Many students struggle with writing essays. Some have not received quality instruction in the process of essay writing, or they may be too overwhelmed with the demands of day-to-day life to be able to focus on creating quality essays. Professional essay samples can be an invaluable tool if you find yourself really stuck. As long as you choose a good writing service, a sample can be instrumental in moving you quickly from staring blankly at your computer screen to creation of a real masterpiece. Here are the ways how a professional essay sample can help you with the writing process. 1. Choosing a Topic Are you completely stuck on trying to come up with the right topic for your paper? This initial step can feel daunting and often prevents the most well-intentioned students from even starting. But a sample essay can point you to the right direction and make you think about some great possibilities. It can even help you with that other daunting initial task coming up with a thesis statement. 2. Writing a Strong Opening The first impression is quite powerful. That’s why any expert will tell you that the most important part of any piece of writing is the first paragraph. The opening is the place where you either capture the reader’s attention or completely lose it. How does the professional sample essay begin? Does it have a strong hook that gets the reader’s attention? Does it state the purpose of the essay clearly so that the reader feels that it has a clear direction? Use these tactics while constructing your own first paragraph. 3. Organization Well-written essays have a logical flow and they are organized in a clear manner, with several main ideas and relevant supporting details for each of these. Imagine how an outline would look like for this sample essay, and use it while creating your own outline. 4. Sources Research can often be the most challenging aspect of the writing process. It’s difficult to know where to find reliable sources that can be used to support your thesis statement. The sources cited in your sample essay can give you an idea of where to start. 5. Proper Citation It can be confusing to master various citation styles. Some instructors require APA, others MLA. These look very different. Reading the rules or hearing a description of them isn’t all that helpful. You need concrete examples to give you confidence that you cite sources for your own paper the right way. 6. Transitions It is an art to make smooth transitions in an essay. You need a few well-placed transition words and an effortless segue from one paragraph to the next one. Easier said than done, right? Follow the sample essay and you will see how easily you tackle this issue. 7. Word Choice Good writers always know the right words to evoke certain emotions in their readers. Take note of the strong words used in your professional essay sample and how they impact you as a reader. Use this to get some idea of the kind of language that will be especially strong and effective for your own essay. 8. Argumentation Skill A good writer can skillfully argue their position. What are the techniques that the professional essay writer use to persuade readers to his/her point-of-view? You can use some of these strategies to develop your own argument. So don’t waste any more time feeling stuck wondering what to write and how to write it. Trust a professional to guide you in the process and make it less painful and more inspiring.

Transformations of Thailand Research Paper Example | Topics and Well Written Essays - 3250 words

Transformations of Thailand - Research Paper Example However, this has undergone change. The civil society gas grown and this has developed a participatory political structure in Thailand. This environment has triggered greater abiding of the rule of law and has implemented a system which is more balanced and effective (Thailand Country Report, p.14). The urban elite society has evolved which remains well connected with the senior bureaucrats, international donors and politicians. The loosely cohering and fragmented party system in Thailand has been restructured. The Democratic Party has become highly institutionalized. The number of parties has increased from 1.65 in 2005 to 6 in 2007 and party fragmentation has also increased. The party system was characterized by multi-member system of district election. The civil society has been evolving and is getting more connected to the business associations, bureaucrats and political parties. The workers’ union has been given greater say and responsibility. The NGOs have grown in impor tance. They have also formed alliance with the top bureaucrats and political leaders. The conditions of female workers and children have improved over the years. In the rural areas, the responsibility of self-organisations has increased. The village community has become more cohesive and their actions have become more collective in nature (Thailand Country Report, p.13). ... The Government has implemented policies to allow more cultural space for the Thai-Malays. These efforts were primarily made in favor of preserving the cultural identity of both nations and reducing the impact of the armed insurgency. Thailand has witnessed an increase in the number of programs for creating equal right and opportunities among people (The Asia Foundation, â€Å"Resolving Conflict in the South†). The makers of policy have increased their focus on the development of system capabilities to bring about changes in the educational system in Thailand. This has primary aroused out of the response of the global response to the increasing gap between traditional educational capabilities and the demands of the information system (Hallinger & Kantamara, â€Å"Introduction†). The Thai schools have introduced lessons on cross cultural studies. The country has become more competent in its ability to adapt to changes. Efforts are being made to build the nation’s a bilities to adapt such capabilities. Political Thailand has been undergoing dramatic political transformation. The changes have been incorporated to strengthen the democratic institutions and also as a conflict resolving measure that has been occurring in the Muslim dominated provinces in the southern provinces. The provinces of Yala, Pattani and Narathiwat happen to be predominantly occupied by Muslims. The states lying between Buddhist Thailand and Muslim Malaysia are diverse in terms of culture, linguistics identity from the two countries. The development of government policies in Thailand is ethno-centric which has alienated the Muslim community and aroused armed militancy. Transformation programs have evolved for creating and maintaining equal rights and opportunities in favor of the Muslims (The Asia

Cloud computing Research Paper Example | Topics and Well Written Essays - 500 words

Cloud computing - Research Paper Example It is clear that organizations are moving to this direction as data storage for the future. Cloud computing is one of the most essential concepts that will continue to play a dramatic role in the modern century. Cloud computing is undoubtedly a vital components for organization as it upholds security, embeds flexibility and allows corporations to implement a modern IT system. In essence, cloud computing is a cluster of servers that function together. Moreover, number of characteristics that define cloud data, applications services and infrastructure. For instance, cloud services can be remotely hosted. In addition, they are ubiquitous, meaning Services or data are available from anywhere. When it comes to cloud computing, many flavors are present. Research shows that cloud computing is beneficial to most companies because it is cost efficient, offers unlimited storage and is easy to maintain and upgrade. Another great feature of the cloud is the fact that it can provide services for end-users. One of the notorious services is known as Platform as Service(Paas). In the PaaS model, cloud providers deliver a  computing platform  typically including operating system and programming language. MVC framework is a prime example of this service. Moreover, Infrastructure as Service or (IaaS) or IaaS clouds often offer additional resources such as virtual machines, storage capacity, security and end-to-end logical network model. Lastly, Software as Service (SaaS) can be beneficial because of a software deployment where an application is hosted as a service. A great example of this is Salesforce 2.0 in the e-commerce realm. A great benefit of cloud computing is the fact is the fact that it takes high energy costs. In addition, the traditional mainframe networks take too much space. Furthermore, the heat that is generated through these servers must be cooled. In fact, recent studies have found that organizations achieved on average an 18% reduction in their budget

ASTRONAUTICS & SPACE Essay Example | Topics and Well Written Essays - 250 words

ASTRONAUTICS & SPACE - Essay Example The purpose of ISS includes functions like investigating affect of weightlessness on biological species, including crew members, over a period. In addition it will also study crystal growth in space. (Oberg, 2005). NASA had originally scheduled participating in ISS program until 2015, but with loss of STS-107, President Bush declared that the shuttle would be retired by 2010, which meant no support service for ISS. Hence, its plans for last module launch, as well as, de-orbiting procedures are not yet clear.(Catchpole: The international Space Station) These rovers have greater mobility than 1997 pathfinders. While each rover can trek up-to 100 meters, across the red surface on one Martian day, it could carry sophisticated instruments that can help in discovery of water on Mars. The landing procedure for both rovers and pathfinders are almost identical. (Mars Exploration Rovers). However, the landed portion of rovers has different design that allows carrying all instruments with rover. Pathfinders carried instruments on Lander and a small sojourner rover. Rovers are able to take color and infra-red images with 360 degree visibility. Possibility of presence of water on Martian surface has been the major discovery of the Mars Exploration Rover mission.(Mars Rovers Most Amazing Discoveries) Catchpole John, â€Å"The international space station: building for the future†, book,: Retrieved on 8th Dec 2010 from:

Should drivers pay fine for talking on cell phones or texting while Essay

Should drivers pay fine for talking on cell phones or texting while they drive - Essay Example e increasingly focusing on building mobile phones into car systems, the debate surrounds around not the device being hand-held or hands-free; rather the debate is on the act of phone communication. Although some people may argue about safety regarding hands-free devices, it is the topic of conversation that can distract the attention level of drivers. However, due to the extreme importance of cell phones in modern life drivers do not heed the dangers associated with using the device while driving. Therefore, it is necessary that laws need to be applied to discourage drivers from using cell phones. Despite the conveniences of using cell phones in modern days of communication, drivers should be fined for talking and texting while driving because doing so texting and talking increases the probability of accidents, they put lives at danger, and they are a driving distraction. Texting and talking while driving increase the probability of accidents. Let me begin by giving some statistical figures to prove my point of argument. According to an estimation given by CDC report, every day in the United States 9 people meet with fatal accidents and 1,153 people get injured as a result of mishaps caused by a distracted driver. A driver becomes distracted when he remains busy doing activities other than driving that include talking on the cell phone or texting. A study was conducted by CDC in 2011 to analyze the reasons of distraction. It was revealed that 69 percent of U.S. drivers between the age of 18 to 64 have talked on their cell phone while driving in the 30 days prior to the study. In Europe, it was 21 percent in UK and 59 percent in Portugal (â€Å"Distracted Driving†). According to another 2011 report by National Highway Traffic Safety Administration (NHTSA), distracted drives attribute towards 22 percent of injuries and 16 percent of deaths by ro ad accidents (Trempel et al., 6). In another report published by the U.S. government, in the year 2008, 6,000 people have

Humorous exhumation hypocrisy in Moliere's Tartuffe Essay

Humorous exhumation hypocrisy in Moliere's Tartuffe - Essay Example For an instance, the US involvement in the Iraq War can be described satirically as following: Mr. Bush, the President, along with his whole Army led an enterprise in Iraq to beat in the bush. But what he got there ultimately kept him busy with beating about the bush in America. Finally, the innocent Americans with blood-washed hands raised their voice: â€Å"Mr. Bush! Will you please stop beating around the bush? Now It is time to hear about the truth!† The salient ingredients of satire are humor, criticism and moral tone. The object of satire can be any foul and objectionable idea, concept and practice in either an individual or a group. The main literary tool of satire is the use of both sarcastic and mild ironies, sarcasm, exaggeration, etc. But sarcastic satires often pivot on bitterly cynical denunciation that tends to injure its intellectual brilliance. For example, if one says, â€Å"Once upon a time, in Iraq the Americans would chop the tender Iraqi boys and girls and prepared the dishes for the leaders†. This line is not satirical; rather it is sarcastic because it lacks humor as well as wit. Yet a satire can refer to some socially acknowledged taboos such as obscene sexuality, invectives against religion, etc. Griffin Dustin defines satire as following: Satire is a wit contest, a kind of game in which the participants do their worst for the pleasure of themselves and their spectators. . . . If the exchange of insults is serious on one side, playful on the other, the satiric element is reduced. (Dustin 23) Indeed a satire attacks foolishness, follies, vices, wrongs, etc by making fun of them wittily. Moliere’s â€Å"Tartuffe† is such a successful satire that humorously criticizes the religious hypocrisy during the latter half of the Seventeenth Century. Moliere has declared the moral purpose of the play in bold line in the preface of the play: â€Å"distinguish clearly the character of the hypocrite from that of the truly devout man† (Moliere 2). On the surface level, he depicts Tartuffe as a devoutly religious character. But the underlying message of the play is that Tartuffe is ultimately a fraud under the religious apparel. Obviously in the play, the object of his satire is to criticize the late seventeenth century religious hypocrisy with humor and wit. The most remarkable passage that is significant for its role in the satire as a whole is as following: Your husband? Why concern about that rube? He drinks in every story like a boob! If he caught us, en flagra nte, that dull lout, He'd offer up to God a joyful shout! And even when he realized, that clown, He'd chastise you, be careful of your gown! (Act IV Scene V) This passage -in fact, one of Tartuffe’s speeches- is the most precious part of the satire as a whole. Its satirical role is double-folds. On one hand, it exhumes the filthy nature of Tartuffe before his most devout follower, Oregon, who is hiding beneath the table. Indeed such exhumation of Tartuffe’s fraudulence before his most obedient devotee significantly refers to the witty and humorous exhumation of the hypocrisy of Moliere’s contemporary religious institution. On the other hand, it criticizes the blind faith of Oregon, generally the commoners while evoking the convulsion of laughter of the audience. Obviously Oregon stands for the death of common sense that is an essential part of a satire. At the beginning of the play he has been fooled by Tartuffe and remains befooled till this episode. Therefore this passage also contains the moral and pedagogic part of Moliere’s satire. Here Moliere opens Oregon’s as well as the audience’s eyes. In this passage, it is as clear as broad daylight to both Oregon and the

Should drivers pay fine for talking on cell phones or texting while Essay

Should drivers pay fine for talking on cell phones or texting while they drive - Essay Example e increasingly focusing on building mobile phones into car systems, the debate surrounds around not the device being hand-held or hands-free; rather the debate is on the act of phone communication. Although some people may argue about safety regarding hands-free devices, it is the topic of conversation that can distract the attention level of drivers. However, due to the extreme importance of cell phones in modern life drivers do not heed the dangers associated with using the device while driving. Therefore, it is necessary that laws need to be applied to discourage drivers from using cell phones. Despite the conveniences of using cell phones in modern days of communication, drivers should be fined for talking and texting while driving because doing so texting and talking increases the probability of accidents, they put lives at danger, and they are a driving distraction. Texting and talking while driving increase the probability of accidents. Let me begin by giving some statistical figures to prove my point of argument. According to an estimation given by CDC report, every day in the United States 9 people meet with fatal accidents and 1,153 people get injured as a result of mishaps caused by a distracted driver. A driver becomes distracted when he remains busy doing activities other than driving that include talking on the cell phone or texting. A study was conducted by CDC in 2011 to analyze the reasons of distraction. It was revealed that 69 percent of U.S. drivers between the age of 18 to 64 have talked on their cell phone while driving in the 30 days prior to the study. In Europe, it was 21 percent in UK and 59 percent in Portugal (â€Å"Distracted Driving†). According to another 2011 report by National Highway Traffic Safety Administration (NHTSA), distracted drives attribute towards 22 percent of injuries and 16 percent of deaths by ro ad accidents (Trempel et al., 6). In another report published by the U.S. government, in the year 2008, 6,000 people have

Medication Errors, Safety, Prevention and Reporting Essay

Medication Errors, Safety, Prevention and Reporting - Essay Example Medication errors that can lead to harmful effects on the patients can be prevented if nurses take the proper responsibilities of safety and reporting. Medication errors, particularly related to nursing, are defined as the errors that might lead to improper use of medication, causing harm to the patients, when the patient is in charge of some healthcare professional or nurses (Medication Errors, 2013). Medication Errors, Safety, Prevention, and Reporting:While medication errors may occur at any place, it has been found that the errors most commonly occur even when patients are in charge of any doctor, in nursing homes, under the case of nurses. It is highly essential and recommended to consult doctors before taking any medication in order to avoid harmful effects or injuries resultant from wrong medications. An example of medication error is intake of a prescription painkiller along with a non-prescription painkiller. In such cases, the dosage exceed the limit that should be taken an d thus cause damage to the livers. Thus safety measures need to be taken in order to avoid such errors in medication. Having a proper communication between the doctor and the nurses is one of the safest ways to clearly understand which drug is being provided to the patients (Medication Errors and Safety, 2010).It has been obtained that such medication errors can be prevented if certain cautious measures are considered. In many cases, the doctor may prescribe a wrong medicine, or the pharmacist may provide with a wrong drug. In such cases the nurses take the role to catch the wrong being taking place and protect the patients from the wrong treatments. However, when nurses make such mistakes themselves, they might have to pay for their mistakes. It can be considered that nurses being humans, mistakes might occur by them as well. Thus it is necessary to take certain steps that can at least minimize such mistakes, particularly when the lives of patients are at cost. For this purpose, th ere are certain rights of medication administration that if followed by the nurses can prevent such errors (Lampert, 2012). These rights include checking with two identifiers to ensure that the right medication is being provided to the intended patients. The names and the dates of birth of the patients should be checked in such cases along with checking the history of the patient. Checking the medication is another step that ensures that the intended medication is only provided and has not been mistaken with any other drug. The nurses should also check the appropriateness of the medication, and also the correctness of the amounts of the medications being offered to the patients (Lampert, 2012). These are some of the medication administration rights that need to be followed effectively by nurses in order to avoid medication errors. Some of the other preventive measures that can avoid medication

Communication - Pizza Essay Example for Free

Communication Pizza Essay Introduction Pizza Hut is based in Wichita, Kansas USA 19581. A woman and her two sons created pizza recipes. From here, a family friend advised the sons to open their own Pizza Parlor. 2. Pizza Hut is one of the flagship brands of Yum! Brands, Inc. , which also has KFC, Taco Bell, AW and Long John Silver’s under its umbrella. Pizza Hut is the world’s largest pizza chain with over 12,500 restaurants across 91 countries 3. In India, Pizza Hut has 133 restaurants across 34 cities, including Delhi, Mumbai, Bangalore, Chennai, Kolkata, Hyderabad, Pune, and Chandigarh amongst others. Yum!is in the process of opening Pizza Hut restaurants at many more locations to service a larger customer base across the country 4. Borrowing $600 from their mother, the two brothers purchased second-hand equipment and rented a small building on a busy intersection in Wichita, Kansas. The result of their efforts was the first Pizza Hut and the foundation for what would become the largest and the most successful pizza restaurant in the world 5. Pizza Hut franchisees exemplify the entrepreneurial spirit, which launched their system back in 1958. Through interest and initiative, the Pizza Hut system was able to develop new territories in the United States and overseas. Today, franchisees and joint-venture partnerships account for more than half of the Pizza Hut systems total units. Their development on the international front is a good indication of the growth that has characterized their system. Following the opening of the first international restaurant in Canada in 1968, the Pizza Hut restaurants quickly appeared in Mexico, South America, Australia, Europe, the Far East and Africa. Today, Pizza Hut operates in more than 100 countries and territories throughout the world 6. When Pizza Hut opened its outlet in Baroda, Gujarat they firstly thought that they should make a new pizza to the recipe of the local style in order to attract the local population. g They decided to provide the pizza according to the customer’s taste of choice7. This essay aims to answering the following question: â€Å"Should Pizza Hut open a new outlet in Baroda? † 1. http://www. pizzahut. com/OurStory. aspx 2. http://www. pizzahut. com/OurStory. aspx 3. http://220. 226. 195. 78/pizzahut. co. in/about_us. php 4. http://220. 226. 195. 78/pizzahut. co. in/about_us.php 5. http://www. pizzahut. com/OurStory. aspx 6. http://www. pizzahut. com/OurStory. aspx 7. (Manager of Pizza Hut). Personal interview RESEARCH QUESTION Pizza Hut is an established brand all over India. To increase the growth of the new outlet, Pizza Hut recently set up a new market research on the outskirts of Baroda with the investment of __ Basically, Pizza Hut firms in India send Managers to spread proper awareness about their new outlet among the customers through different types of advertising and keep the customers informed about their advancements in current outlets 10. Commercially, I expect that the opening of the new branch will lead to an increase in sales in Baroda, Gujarat, and could increase the market share of Pizza Hut. For this reason, they want to be able to successfully market their new firm when it is commercially launched. As previously mentioned, to increase its growth and successfully market their upcoming outlet, Pizza Hut has been reviewing various promotion strategies like price reduction, to increase the price in their marketing budget and increase in number of staffs 11. So increasing the production by opening the new outlet and to increase the number of staff to work in both of the outlets is a strategy that Pizza Hut is strongly considering in order to increase their growth in the domestic market 12. 8. (Manager of Pizza Hut). Personal interview 9. (Manager of Pizza Hut). Personal interview 10. (Manager of Pizza Hut). Personal interview 11. (Manager of Pizza Hut). Personal interview THEORETICAL FRAME WORK The Growth of a business can be measured in many different ways such as assets, sales revenue, operating profit, market share, value added, and number of employees 13. As information of pizzas is involved, Pizza Hut believes that what they bring new in the market is not compared with any of the products of any another firm which is selling pizza’s14. I commercially expect that the opening of the new firm will lead to increase in sales in Baroda, Gujarat, and could increase the market share of Pizza Hut. Due to this, they want to be able to successfully market their new firm when it is commercially launched. Pizza Hut aims to convince the customers to set down their new business, (target market) 15. The other promotional method used by Pizza Hut and to spread the awareness about their new outlet is to do market research. I did the market research for Pizza Hut so that they can locate their new outlet where there are more potential consumers. High income group was also asked about the opening of a new outlet, before it is brought up in the market. Pizza Hut believes that the methods used to research on opening a new outlet take hold of the attention of the customers for long time, so that they can visit the outlet frequently16. For reasons mentioned above, growth is widely regarded as the most favorable method to increase the profit level. 12. http://www. tutor2u.net/business/presentations/strategy/businessgrowth/default. html 13. (Manager of Pizza Hut). Personal interview 14. _________ 15. (Manager of Pizza Hut). Personal interview 16. (Manager of Pizza Hut). Personal interview METHODOLOGY To reach a suitable conclusion, an in-depth qualitative and quantitative analysis shall be conducted by using different business tools to the primary data as well as the secondary data collected. The primary data contains the interview of the Manager of the Pizza Hut outlet which already exists, the opinion of the customers who visit the exiting outlet and a few other people. Market research: This will contain the content of the market research and what it entails. This was conducted by me. Analysis of market research: This will contain the graph and an explanation about how many people will visit the new outlet (assumption) from the old outlets daily earning. Swot analysis: This will contain the strength, weakness, opportunity, and threats of the business for opening the new outlet. Ansoff’s matrix: A model which identifies growth strategies for a business and it is based on an analysis of their products and their market. Pest-g: This will identify the political, economical, social and technological, as well as the environmental problem of the firm. Cost analysis: Cost analysis will be conducted to find out the quantifiable and unquantifiable cost involved in increasing the personal selling. MARKET RESEARCH Market research is the collection, collation and analysis of the data relating to the marketing and consumption of the goods and the services18. Market research helps in opening the new outlet, tells us were we stand in the market and how we can improve. How many times does the customer visit Pizza Hut? Group of people |More than once a week |Once a week |Fortnight |Monthly or less | |Family |04 |20 |45 |25 | |College students |35 |50 |36 |19 | |Above 50 |00 |05 |36 |30 | |Teenagers |40 |45 |26 |17 | (18) Here the market research data is organized according to age group. |Market research done of the location |Yes |No | | |(%) |(%) | |Sayajigunj |66 |34 | |Karelibaug |68 |32 | [pic] Here I have conducted the market research for the two different areas and I have come to a conclusion that in Karelibaug there are 90% of people saying yes to open the new outlet 20. This is due to one outlet of Pizza Hut not providing delivery services to distant areas21. So if it is in that area then many people can visit the outlet and this will give more profit to Pizza Hut. As people from Fathegunj, Sayajigunj, city area and Karelibaug can visit as it will be nearer to them 22. 17. market research done by interviewing different people 18. business studies book by Dave hall pg 147 19. interviewing different age group of people 20. People gave reason that why in these two areas. 21. Told by the people staying in that area. ANALYSIS OF THE PRIMARY DATA The finding of the market research which I have done for Pizza Hut will be analyzed to identify specific market attributes such as the manner in which the customer will respond more. In addition to this, it will identify important information such as the effectiveness of the market research results given by the customers will be discovered. From this data, it will be possible to judge the weaknesses of Pizza Hut. Recommendations will then be made by me on methods which Pizza Hut can adopt to overcome these weaknesses. Once Pizza Hut overcomes these weaknesses, it will have a better chance to successfully market their new outlet, and at the same time increase the sales from their current outlet. The graph below compares the frequency of teenagers who visit Pizza Hut as opposed to college students. [pic] 22 The ratio of college student is more than teenagers23. This means that on an average, college students visit Pizza Hut more compared to the teenagers. This graph tells us how many families and those above 50 wish to go to Pizza Hut. [pic]24 22. market research done by interviewing different people 23. (Manager of Pizza Hut). Personal interview 24. market research done by interviewing different people SWOT ANALYSIS Swot analysis: swot analysis is an analysis of the internal strength and weaknesses and the external threats and opportunities that Pizza Hut faces. The swot analyses will illustrates how the external opportunities and the threats can be matched with the Pizza Hut’s internal strength and weaknesses to result in a set of possible strategic alternative. This would identify Pizza Hut’s distinctive competencies and the opportunities that the Pizza Hut is not currently taking a due to lack of appropriate resources swot means : S-strength W-weaknesses O- Opportunities T-threats Strength(S): these are the things which I observed, Pizza Hut and their staff do and which is the strength for them: They are well known for their pizzas 26. They provide good quality, taste and quick service 27. Their good service; grooming, cleanliness, and good interaction with the customers make customers want to visit them again 28. Due to their good taste and grooming, the other domestic pizza outlets try to compete and learn from Pizza Hut 29. Reputed brand, market excepted very easily, Due to the above, Pizza Hut makes good profit30. Pizza Hut has the ability to provide it’s customers with deals, offers and specials so that they can save money and get more value. This is a strength for the organization as it makes customers purchase more while receiving more value for their money. Customers use these vouchers and specials when ordering in bulk or for everyday orders. Weaknesses (W): these are the things which I observed and Pizza Hut does poorly and in which they can be affected are: During the weekends, Pizza Hut is full of customers, during that time the service is poor 31. There is little to no place for the people to sit who are waiting to be seated32. Availability of other multinational outlets like Mac Donald and Dominos will be the competitors of Pizza Hut too. 33 Opportunities (O): the directions which the business could take in future like: By opening a new outlet there will be an opportunity for growth of the business and development for employees34. If a person was previously employed by Pizza Hut and has passed the Pizza Hut course with the appropriate certificate, then they are able to receive double their salary35. Pizza Hut is a branded and a multi-national chain, therefore it allows staff salaries to be double that which is offered to other staff in other company’s36. Threats (T): the threats to a business arise from the activity of the competitors and failing to take opportunities like: Pizza Inn is the domestic pizza outlet in Baroda; both of them are doing very good profit-wise therefore Pizza Inn is a threat for Pizza Hut37. Pizza Inn is a well-known organization to the Baroda community as it also provides good quality and taste and this is a threat to Pizza Hut as this is one of Pizza Hut’s strengths. 25. business studies book by Dave hall pg 38 26. http://www. tutor2u. net/business/strategy/SWOT_analysis. htm 27. (Manager of Pizza Hut). Personal interview 28. (Manager of Pizza Hut). Personal interview 29. (Manager of Pizza Hut). Personal interview 30. (Manager of Pizza Hut). Personal interview 31. (Manager of Pizza Hut). Personal interview 32. (Manager of Pizza Hut). Personal interview 33. (Manager of Pizza Hut). Personal interview 34. interview taken while doing market research 35. (Manager of Pizza Hut). Personal interview 36. (Manager of Pizza Hut). Personal interview 37. (Manager of Pizza Hut). Personal interview 38. (Manager of Pizza Hut). Personal interview THE ANSOFFS MATRIX The ansoff matrix: The Ansoff Growth matrix is a tool that helps businesses decide their product and market growth strategy38. Ansoff’s matrix will allow the firm to consider the alternatives open to it for entering a new market or entering new product into the market39. Product | |Existing |New | |Existing |Market penetration |Product development | |New |Market development |diversification | Market Market penetration: market penetration is used to achieve the growth in the existing market with the existing product40. Market penetration uses the marketing mix to push the product which is gaining as much as market share and as quickly as possible41. Market penetration seeks to achieve four main objectives: Increase usage by existing customers, maintain or increase the market share of current products42. Pizza Hut is the branded outlet so that people use the substitute outlet less (Pizza Inn, u s pizza, Uncle Sam’s Pizza, and Dominos). Pizza Hut encourages customers to use their outlet more regularly by providing new taste to the customers43. Product development: this is concerned with marketing new or modified products in the market for the customers 44 like: Normal pizzas intend to act as a replacement for the new product which will be introduced45. Market development: this involves the marketing of the existing product in the new market such as: As Pizza Hut has one outlet already in the market, they will open a new outlet in Baroda but in a different area. They will introduce some new products when they open their new outlet. However, they will need to continue the marketing of their old and classic products along with the new products46. Diversification: this will occur when the product is developed for the new market. Diversification allows a business to move away from the trust upon the present market and product47. 38http://www. tutor2u. net/business/strategy/ansoff_matrix.htm 39oxford study course book by jo toy pg 32 39. http://www. tutor2u. net/business/strategy/ansoff_matrix. htm 40. business studies book by Dave hall pg 239 41. oxford study course book by jo toy pg 32 42. http://www. tutor2u. net/business/strategy/ansoff_matrix. htm 43. (Manager of Pizza Hut). Personal interview 44. (Manager of Pizza Hut). Personal interview 45. Manager of Pizza Hut). Personal interview 46. business studies book by Dave hall pg 239 PEST –G ANALYSIS Pest g: this will look at the external environment and the global factors that may or will affect a business. It can provide a quick and visual representation. It is usually divided into five external influences on a business-political, economic, social, and technological and green46. Political: this is concerned with how political developments, regionally, nationally and internationally might affect a business’s strategy47. Political development is not so relevant in this instance as Pizza Hut has an existing established branch which is not affected by this external factor, the political issues are not so important because they do have the outlet in India and Baroda. For opening the new outlet government factors are not important as it already has opened one outlet48. Economic: this might include the analysis of a variety of economic factors and their effect on business they include: consumer activity, economic variable, government policy, the effect of change in product and labor markets49. Pizza Hut’s outlet which is Baroda, Gujarat has competitors in Baroda, Gujarat50 however, these are not Pizza Hut branches – they are other competitors such as Dominos and Pizza Inn. These have an economic external influence as it affects the consumer activity as customers may prefer to go to Dominos if there is better service, quality and price offered. The new place suggested trough market research, there mainly the people with their families and above 30 will visit. It is not that the youth’s wont visit but there are less youth’s in that area compare to the area where the current Pizza Hut is located. Social: how is Pizza Hut affected socially? It is not likely that Pizza Hut will be affected socially as each age group visit’s Pizza Hut51. Due to the location of the old Pizza Hut site (located near commercial places) it attracts a lot variety of consumers. The new site will be located in a suburb where there are families therefore the market will be families. When a whole family eats a meal at Pizza Hut, they tend to splurge on extras such as drinks and sides. This is positive for the organization in terms of profit. However, in Karelibaug, families won’t come daily or once a week to have pizza’s so it can be affected socially. Generally in the new outlet older segment people will visite. Technological: Businesses operate in a world of rapid technological change. The organization needs to regularly review the impact of new technologies upon their activities. The product can become old-fashioned quickly. The production method can become out of date52. Pizza Hut looks that how they are different from other firms such as Pizza Inn, Domino’s pizza, us pizza and many other domestic outlets for pizza’s. Even Mac Donald’s is a competitor. One technological factor which could effect the environment is how Pizza Hut creates its products such as the production line in which a pizza is made. 47. business studies book by Dave hall pg 38 48. business studies book by Dave hall pg 38 49. (Manager of Pizza Hut). Personal interview 50. business studies book by Dave hall pg 38 51. (Manager of Pizza Hut). Personal interview 52. (Manager of Pizza Hut). Personal interview. 53. business studies book by Dave hall pg 38 COST ANALYSIS Cost analysis is currently a some what controversial set of methods in program of evaluation one reason for the controversy is that these terms cover a wide range of method, but are often used interchangeably. There are two types of cost associated with hiring new place. They are fixed cost and variable cost. Both these cot will be identified to check the financial growth of the undergoing new outlet. Both are classified as below: Fixed cost Hiring charges foe the new place Salary of the staff Minimum hiring charges of telephone. Variable cost Production cost Office usage Approximately amount of profit for the new outlet May by through which you will be able to fine out pbit (profit before interest and tax), pbt (profit before tax), pat (profit after tax). | | |Per month |Per annum | |Sales | |1350 |16200 | |- variable | |60 |720 | | |contribution |1290 |15480 | |- fixed cost | |45 |540 | | |PBIT |1245 |14940 | |- interest | |78 |940 | | |PBT |1167 |14000 | |- tax | |350 |4200 | | |PAT |817 |9800 | 55 From the above assumption we can conclude that profit on pbit is approximately equals to 65. 60% |1260 |720 | |100 |? | |= 57. 14 | This is the variable cost |1260 |540 | |100 |? | |= 42. 58 | And this is the fixed cost. Variable cost of new outlet is higher than its fixed cost about 14. 12. Contribution of new outlet is about 96% which can be calculated by following formula: |Sales |contribution | |16200 |15480 | |100 |? | |= 96 | 56 Variable cost depends upon number of units of new outlet but the fixed cost is fixed. Cost may also be defined in different class For example: production cost office cost selling and distribution cost We can include raw material cost for the pizza’s and service cost for the pizzas. In production cost all the administration expense and legal and professional charges in office expense. We can bifurcate the transportation of the delivery man and advertisement expenses as selling and distribution charges. Selling and distribution charges can depend on number of unit sold and cost up till cost of goods sold always depends on goods sold57. 55. (Manager of Pizza Hut). Personal interview 56. (Manager of Pizza Hut). Personal interview 57. (Manager of Pizza Hut). Personal interview INVESTMENT APPRAISAL Investment appraisal is the evaluation of an investment project to determine whether or not it is likely to be worthwhile. It is essential to appraise the investment Pizza Hut will undertake and to establish weather it is going to be beneficial. Below are the techniques, which will assist appraising the investment: †¢ Pay back period and †¢ Net present value Pay back period This technique assesses the number of years it will take foe the Pizza Hut to recover all their initial costs. This is a very simple tool as it ignores most of the costs the firm would incur due to opening a new outlet. The cash flow is also an approximate estimate when there are too many variable then Pizza Hut cannot control. They assume that they have more customers and 10% more profit throughout the year than what they had the previous year. There were a few assumptions made for the cash flow. These were that the machine they used to make pizza’s worked at 100% capacity and all products were sold. |Pay back period for the new outlet | |Year |Net cash flow | |0 |-10,00,000 | |1 |2,00,000 | |2 |6,00,000 | |3 |3,00,000 | |3,00,000 |12 months | |2,00,000 |? | |= 8 months | You can get 2,00,000 in 8 months so our net pay back period for investing RS 10,00,000 in new outlet is 2 years and 8 months. Analysis of pay back period. The pay back technique has shown us that it takes 2 years and 8 months to pay back for the new outlet. However, we learn form the market research and swot analysis that there are mainly people above 35 hence it would be smarter from them to do some thing which might attract the youth from other areas and influence them to visit that outlet too. Net present value Net present value incorporates the principle of time value of money by converting payments at different times to the equivalent values at the common reference time. The discount factor used is 4% as the interest they could have got from the bank currently is 4%. I then did NVP. |Year |Net cash flow |Discount factor 4$ |Present value | |0 |-10,00,000 |1 |10,00,000 | |1 |2,00,000 |0. 9615 |1,92,300 | |2 |6,00,000 |0. 9246 |5,54,760 | |3 |3,00,000 |0. 8890 |2,66,700 | Analysis of net present value The new outlet will generate ____ amount after 5 years. ORGANIZATIONAL CHANGES To effectively deal with the increase in the growth by expansion, it is necessary for there to be some internal changes. It is very necessary that the staff’s grooming should be done properly, so that they can serve the customers in a professional manner. When they open their second outlet from a single, Pizza Hut will have to keep some one on whom they can trust and can rely on and they have to shift a few staff from the present one to the opening one. As they opening a new outlet, they are turning from one into two outlets. Due to this the position of many of the staff’s have been will be changed. This change does not affect their work, they have an effective communication channels among the employees. This could be in the form of giving the staff a proper atmosphere in which they can settle easily, the changes in the outlet and the goals that the Pizza Hut wants to attain. RECOMMENDATION Starting up the new outlet, initially it will not give them that much profit but it will definitely give some. For this: 1. Pizza Hut should shift few of their staff and of course one of the leader to supervise from the existing outlet to the one which will open in the near future. 2. They should appoint few new staff for the existing outlet and also foe the future’s outlet so that the one who are new in the new outlet can get t know more from their seniors who are shifted from the existing business. 3. For marketing about their new outlet they should restructure they method in which the do the marketing. 4. The market research was done on few people in Baroda, Gujarat, and not in the whole of Baroda. So the extensive market research needs to be conducted across the whole Baroda, Gujarat to get the proper kind of information about the location. CONCULSION The report shows that Pizza Hut should pen the new outlet in Baroda, Gujarat, India. If Pizza Hut increases their staff, then it would be in a better position to serve the customers and if they shift few of their trained staff and give training to the new staff to whom they are going to appoint then they would also be in the better position. They should also shift one of the managers to the new outlet so that in case if any problem occurs then they will be able to handle it. The financial aspects of the undertaking are not the problem for the Pizza Hut as it is in a strong financial stage. But the recruitment of the new staff cold affects the staffs. The environment and the working portfolio of the staffs will be changed as Pizza Hut will reconstruct the marketing set-up. So before employing the new staff Pizza Hut should let the old staff settle into their working environment. As previously said, the personal interview were only conducted in Gujarat, and the result of this only represented he view of customers from Gujarat. Hence, the further market research needs to be done to get a broader perspective on this study. The indirect costs associated with the undertaking the project will have to ascertain. As previously mentioned, one indirect cost is that a large recruitment could lead to a decrease in the motivation of the existing staffs. Other indirect cost could be in the form of the training program for the new recruits to a specialist company, so that it is done efficiently. If the new recruits do their job well, serve the customers in the proper way, follow the training properly, are groomed very well and give the best service then this would motivate the customers to visit them again. `Graph showing the frequency of visits to Pizza Hut by college students and teenagers 0 10 20 30 40 50 60 More than once a week Once a week Fortnight Monthly or less time period College students Teenagers graph showing the frequency of visit to Pizza Hut by families and people above 50 0 10 20 30 40 50 More than once a week Once a week Fortnight Monthly or less time period Family Above 50.

Septic Shock Case Study: Causes and Effects

Septic Shock Case Study: Causes and Effects Introduction Septic Shock is a serious circulatory disorder often characterised by a whole- body inflammatory state and the systemic response to infection (Titheradge, 1998), with the most common cause being the contamination of blood with bacteria. Septic shock is defined as sepsis with hypotension which develops in almost half of all septic patients as a complication with a mortality rate of 40-60% (Titheradge, 1998). Septic shock often results in a progressive failure of the circulation to provide blood and oxygen to vital organs of the body resulting in impaired tissue perfusion and oxygen extraction (Thiemermann, 1997). The key symptoms include a severe fall in blood pressure (hypotension) with hypo-reactivity to vasoconstrictor agents (vasoplegia) which may lead to the dysfunction or failure of major organs including lungs, liver, kidneys and brain (multiple organ dysfunction, MODS) and ultimately death (Goligorski et al., 1997). Presently it is widely assumed that septic shock rarely shows similar symptoms in affected individuals and therefore it is difficult to detect and then consequently treat it (Groeneveld and Thijs, 1986). It is, however, also agreed that most of the therapeutic interventions invariably focus on the primary aim of fighting the refractory hypotension by the use of aggressive fluid infusions, glucocorticoids, large doses of vasoconstrictors (Baumgartner and Calandra, 1999) and occasionally renal replacement therapy (Wheeler Bernard, 1999). Yet these interventions do not offer consistent success (Parratt, 1997). In recent times, our understanding of the pathophysiology of septic shock has developed significantly through experimental and clinical trials, though the discovery of a suitable treatment with therapeutic efficacy is proving elusive (Baumgartner and Calandra, 1999). This is probably because of the heterogeneity of the clinical situations and the differences in host response to i dentical pathogens. Moreover evidence suggests that different pathogens which cause septic shock respond differently to the conventional treatments. Still, no effort has been made to treat patients according to the nature of the infecting organism (Gao, Anonymous, 1992). During the early 1990s nitric oxide (NO) emerged as a potentially substantial step towards the treatment of septic shock. This finding directed scientists to carry out numerous clinical trials and animal experiments with the objective of finding out more about the interrelation of NO and Sepsis (Cobb, 1999; Kilbourn, 1999). Later, the discovery of nitric oxide synthase (NOS) made this enzyme the primary target of therapeutic agents (Rosselet et al., 1998). However, recently a substantial amount of literature has been published with evidence contradicting the discoveries of earlier studies. Today more than a decade has elapsed without any resolution to the matter and even in this 21st century Septic Shock is invading the developing countries rapidly (Cobb, 1999; Kilbourn, 1999). This problem of a lack of significant advances in this field can be highlighted by the fact that 17 years have passed since the final publication of the Consensus Conference on sepsis and sepsis related syndromes (Rangel-Frausto, 2005). This paper conclusively defined sepsis and its symptoms with the hope of finding a suitable treatment in order to eradicate the disease (Rangel-Frausto, 2005). Today, however, the situation has not changed significantly with up to 750,000 new sepsis cases every year and 215,000 annual deaths in the United States (Trzeciak et al., 2008, Mitchell M. Levy, 2007). Additionally, in the population that survives such attacks, there is considerable morbidity with many scoring low in health related quality of life assessments (Kaarlola et al., 2003, Perl et al., 1995). Hence the 5 million lives campaign instigated by the US Institute of Healthcare Improvements, aims to minimize the prevalence of nosocomial sepsis (sepsis originating in a hospital) (Gao et al., 2008). This campaign aimed specifically at increasing safety and transforming the quality of hospital care (McCannon et al., 2007). Moreover, the Surviving Sepsis Campaign aims to improve the quality of life of septic patients using the best evidence available currently (Dellinger et al., 2004). Though the world mortality rates have declined in recent times, sepsis is gradually becoming more prevalent in the elderly in the developing countries (Gao et al., 2008).This is mainly due to the extended longevity of patients with chronic illnesses, the increased occurrence of immunosuppression, and the more frequent use of invasive procedures (Bone, 1991; Parrillo, 1993). Sepsis, severe sepsis, septic shock and multiple organ failure still dominate the mass cases of non coronary intensive care units (ICUs). This essay will attempt to explore the fundamental mechanisms leading to tissue and organ damage in septic shock through the investigation of a case study. Following this, the discovery and general biology of nitric oxide (NO) shall be discussed, and the experimental evidence implicating NO as an effector in sepsis, will be examined in detail. The results obtained from various pharmacologic interventions directed at NO in animal studies will also be considered. This report will also give an account of conventional and innovative treatments for the management of septic shock. Finally, data from the few available relevant clinical trials will be reviewed and possible future avenues of interest will be discussed. Systemic Inflammatory response syndrome and Septic Shock (Clinical Manifestation) Sepsis, severe sepsis and septic shock were inaccurately defined until a recently reviewed consensus conference in 1992 (Bone et al., 1992, Dellinger et al., 2004). In this meeting the term systemic inflammatory response syndrome (SIRS) was invented insinuating a clinical response arising from a nonspecific tissue damaging event (insult) (Rangel-Frausto, 2005). Sepsis as mentioned earlier is the result of substantial release of inflammatory mediators in response to an infection. However, often the same mediators are released in the absence of a documented infected in several medical conditions such as cardiopulmonary bypass (Wan S. et al., 1997), pancreatitis and trauma (Shanley TP. et al., 2006). Due to this, the early definitions of sepsis or septic shock were found to be misleading hence a North American consensus conference proposed a new terminology. In this conference sepsis was defined as a condition in which critically ill patients meet criteria for SIRS, in the context of infection. SIRS was defined as two or more of the following: 1) heart rate >90/min; 2) temperature >38Â °C or 12,000 or 20/min or a PCO2 3.5 L min-1 M-23; 2) hyperglycaemia (plasma glucose >120 mg/dL) in the absence of diabetes; 3) significant oedema or positive fluid balance (20 mL/kg over 20 h); 4) inflammatory variables: plasma C-reactive protein >2 SD above t he normal value or plasma procalcitonin >2 SD above the normal value and 5) mixed venous oxygen saturation (SVO2) >70% . (Dellinger RP et al., 2004). SIRS is generally not considered as a disease and its recognition does not provide any clinical conclusion. However, since it has proven to be a very useful for the identification of sepsis and its sequelae namely severe sepsis and septic shock it is regarded as a very important tool (Shanley TP. et al., 2006). Case Study: A 3-year-old boy was admitted to the intensive care unit because of fever, hypotension, and lethargy. A purpuric rash was noted on his arms and legs. Arterial blood gas analysis demonstrated hypoxemia and metabolic acidosis. The arterial lactate level was 10 mmol/L. He was intubated, resuscitated with crystalloid solution, started on broad-spectrum antibiotic therapy, and given dopamine to maintain a MAP above 55 mmHg. His chest radiograph revealed bilateral interstitial-alveolar infiltrates with a left sided predominance. Gram stain of the cerebrospinal fluid showed gram-negative cocci. The dopamine infusion was increased to 18Â µg kg-1min-1 for persistent hypotension and oliguria. Pulmonary and radial arterial catheter data yielded the following blood pressure, 85/30 mm Hg; MAP, 48 mm Hg; heart rate, 140 beats per minute; CVP, 10 mm Hg; pulmonary artery pressure, 22/14 mm Hg; PCWP, 12 mm Hg; cardiac index, 2.5L min-1m-2; and SVRI, 1226 dyne-sec-cm-5m-2. The boy was treated with ad ditional saline and an epinephrine infusion, which increased the MAP, cardiac index, and urine output. Arterial lactate levels decreased over the next 12 hours. Subsequent cultures of blood and cerebrospinal fluid grew Neisseria meningitidis. In this case the patient with acute organ failure and hypotension was diagnosed with septic shock. The young boy with meningococcal septic shock had a borderline-low cardiac index. Due to this a decrease in the cardiac index in this patient by the administration of an NOS inhibitor might not be desirable. This is suggestive of the fact that NO or its synthesising means cannot always be targeted in order to battle septic shock. I will attempt to go into further details with regards to this statement as we go along the essay. Nitric Oxide discovery: Joseph Priestly first identified gaseous NO in 1772. NO also named Nitrogen Monoxide is a very simple and tiny molecule consisting of one nitrogen and one oxygen molecule. Unknown of its fundamental physiological roles in the mammals, until the 1980s NO was widely considered as a mere toxic atmospheric pollutant (Konstantin J. Ovodov et al., 2000). In the 1980s researchers were examining how blood vessels expand (dilate) hence regulate the mean arterial blood pressure. Dilation of blood vessels, also termed vasodilation is a very important physiological response which partly regulates the blood pressure. By increasing the diameter of blood vessels, vasodilation causes the blood to travel more freely due to lower resistance (RF Furchgott, 1980). Since the blood vessel lumen widens during vasodilation, the blood imposes less outward pressure on the vessel wall hence reducing the blood pressure. In opposition, vasoconstriction reduces the diameter of the lumen increasing the BP. These physiological responses occur all the time in the human body regulating the BP and therefore are one of the most fundamental mechanisms of the human body. Dr Robert Furchgott and his group, later in 1980s investigated the role of acetylcholine in the smooth muscle relaxation and found that relaxation only occurred if a special class of cells called endothelial cells were present (RF Furchgott, 1980). These cells line the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. Behind the endothelial cells are the smooth muscle cells which either relax or contract thus regulating the vascular tone (RF Furchgott, 1991). The same research group also discovered that smooth muscle were only able to vasodilate the blood vessels in the presence of endothelial cells. This indicated that there was some kind of factor that was being released by the endothelial cells which was involved in the dilation of the blood vessel. This factor was named Endothelium Derived Relaxing Factor (EDRF) and subsequently specified as NO (S Moncada et al., 1997). In 1977, Ferid Murad independantly investigated the mechanism of action of nitroglycerin and found that it worked by inducing the release of NO which in turn was able to cause relaxation of smooth muscle cells (F Murad et al., 1977). Louis Ignarro in 1986 finally resolved the whole perplex of EDRF and NO by declaring that EDRF was in fact NO. It was stated that both molecules showed identical properties when he compared gas Nitric Oxide and EDRF (Ignarro, L. J. Et al. 1987). In 1998, Nobel Prize in Physiology and Medicine was awarded to Drs. Robert Furchgott, Louis Ignarro, and Ferid Murad for their discoveries that vascular endothelial cells make nitric oxide (NO) and that such endothelium-derived NO stimulates cyclic guanosine monophosphate (cGMP) synthesis in the underlying vascular smooth muscle, causing relaxation (Kilbourn, 1999). Since the discovery of NO, vast number of its physiological roles in normal conditions have been reported including in the immune system, nervous system, reproductive system and other cellular functions. It has also been found to play important roles in variety of species ranging from mammals, to insects and plants. Role of Nitric Oxide in Biology Since it was first discovered to play a role in the dilation of blood vessels many new roles for Nitric Oxide (NO) have been discovered. In human body, NO is metabolised by its diffusion into red blood cells where it oxidizes the ferrous iron of oxyhemoglobin yielding methemoglobin and nitrate ions (NO3-) (J.M. Hevel et al., 1994 and Konstantin J. Ovodov and Ronald G. Pearl, 2000). This meachanism limits local NO build up and is particularly important in keeping NO concentration in naomolar range, at least in nonhydrophobic compartments (i.e. outside cell membranes) (Beckman Koppenol, 1996). Nitric oxide has been found to be produced by effectively every cell type in vivo and plays an important role in both controlling the normal function of cells as well as in regulating larger scale processes such as the reproductive, immune and nervous systems. A few of these biological functions for NO are described in more detail below. The Immune System Nitric oxide plays many important roles in the immune system although it is expressed in many cell types following endotoxin or pro-inflammatory cytokine treatment (C. Nathan et al., 1991 and R.G. Knowles et al., 1994). NO, in immune system, is produced in high amounts from specific cells called macrophages. Proceedingly to an infection, chemicals known as cytokines are release in vivo which activate the cells of the immune system such as macrophages, and help guide them to the site of infection (S. Moncada et al., 1991 and C. Nathan et al., 1991). NO produced by the macrophages is toxic to the bacteria and play an important role in their destruction (Fig 1). The production of nitric oxide in this way also helps protect against other types of infection including parasites and viruses (S. Moncada et al., 1991). However, too much nitric oxide production can not only lead to septic shock but has also been implicated in conditions where the immune system is too active autoimmune diseases like arthritis (Jang D and Murrell G A, 1998). The Nervous System Nitric oxide has been shown to be involved in both the peripheral and central nervous system. The three nitric oxide producing isotypes of enzyme (iNOS, eNOS, nNOS) (see section) in humans, one isotype (neuronal NOS (nNOS)) is found almost exclusively in the nervous system (Forstermann et al., 1995). nNOS is thought to be involved in promoting the transfer of interneuronal nerve signals. This is thought to take place by the stimulation of exocytosis (release) of endogenous chemicals called neurotransmitters of one neurone (Moncada et al., 1991; Forstermann and Kleinert, 1995). These NT then diffuse across the synaptic cleft (gap between neuronal terminals) and stimulate the neighbouring nerve cell terminal to transmit the signal (Otto Loewi, 1961). NO has shown to play a substantial role in diseases of the nervous system like Alzheimers and Parkinsons. In both diseases, the inhibition of NO has shown to slow down the progression of the disease in mice (Weill Cornell Team, 2005 and Jo hns Hopkins et al., 2004). Reproductive Biology Nitric oxide is one of the most important molecule in the course of reproduction and is involved in many aspects of it. As well as dilating the blood vessels and thereby helping to regulate maternal blood pressure, NO is also involved in implanting the early embryo in the uterus (Rogers, 1995). During pregnancy, nitric oxide is also suggested promote angiogenesis (a process in which new blood vessels are formed) (RayChaudhury et al., 1996). It is also known to play a role in the survival of trophoblasts (form placenta) (Enders et al., 1978). Furthermore deficiency of NO has been found in patients with preeclampsia (a medical condition in pregnancy) suggesting its partial role in growth of embryo (Yallampalli et al., 1994; Liao et al., 1996). In addition, drugs (Viagra) used to treat erectile dysfunction also affect nitric oxide signalling. Cellular function A notable number of cellular activities can be controlled by nitric oxide including cell division, cell movement and cell survival. The majority of cells in human body have the ability to undergo programmed cellular death. This is a self-destructive mechanism usually called apoptosis which often occurs when a cell is damaged and beyond repair, infected with a virus, or undergoing stressful conditions such as starvation (Kerr et al., 1972). Cells in these conditions go through apoptosis so that they dont hinder the proper functioning of the rest of the tissue. During apoptosis, the structures of the cell break down in an organised manner, forming a packaged cell that is smaller in size so that it can be easily removed by the cells of the immune system (Kerr et al., 1972). Nitric oxide was first shown to inhibit apoptosis hence promoting cell survival in human B lymphocytes (Mannick, J. B. Et al., 1994). Subsequently similar finding were reported in an ample number of other cells. However, high doses of nitric oxide also have deleterious effects. They can be toxic to many cell types and can lead to septic shock and multiple organ dysfunction syndrome (MODS) in which case NO causes cell death instead of promoting cell survival (Beal Cerra, 1994). Nitric Oxide and Inflammation (Pathophysiology of septic shock) This section will deal with mechanism by which wall fragments of Gram-negative or Gram-positive bacteria and other inflammatory agents induce nitric oxide synthase (iNOS) in cells and tissues. Exogenous toxins which enter the circulation stimulate the synthesis and release of a number of endogenous cytokines. During a gram-negative infection which can lead to septic shock, lipopolysaccharide (LPS) and endotoxins present on bacterial wall and many other inflammatory agents bind to a co-receptor (CD14) on the surface of specific immune cells like macrophages, resulting in their activation (J.C. Lee et al., 1996). LPS also bind to LPS-binding proteins which are produced by the liver. These proteins facilitate LPS binding to the CD14 co-receptor of the macrophages. The CD14 co-receptor is activated through the binding of LPS to a toll-like molecule (TLR4), (Re F, Strominger J. Et al., 2001) which is responsible for initiating the transmembrane signaling. TLR2 molecules act in the same way as TLR4, (Leppper PM et al., 2002) though; these are activated by gram-positive bacteria, mycobacteria and yeast. Gram-positive bacteria such as Staphylococcus aureus have further additional wall fragments such as peptidoglycan (PepG) and lipoteichoic acid (LTA). Both PepG and LTA have been shown to synergise to produce the characteristic features of septic shock, MODS and ultimately death in rodent models (S.J. De Kimpe et al., 1995 and G.M. Millar et al., 1997). These effects were not observed with either LTA or peptidoglycan alone, although high doses of LTA can cause circulatory failure but not MODS (S.J. De Kimpe et al., 1995). Gram-positive bacteria may also release other enterotoxins and exotoxins, for example toxic shock syndrome toxin 1, which are involved in the pathogenesis of sepsis (reviewed in (R.C. Bone et al., 1994)). The additional fragments released by Gram-positive bacteria bind to unknown receptors however, like LPS binding, cause the release of proinflammatory cytokines TNF-a, IL-1ß, and IFN-? (Thiemermann, 1997, Titheradge, 1999). These cytokines as well as IL-6 are often produced in response to immune stimulation of macrophages and monocytes hence also in septic shock patients. IL-1 and TNF each occur in two forms, a and ß. TNF- a and both forms of IL-1 are made by activated monocytes and macrophages, whereas TNF- ß is made by activated T lymphocytes (Review by J. Saklatvala et al., 1996). There are two receptors for both IL-1 and TNF and the two forms of each cytokine interact with the same receptors. IL-1 a and ß interact with the type 1 IL-1 receptor for signal transduction, whereas type II does not appear to transmit any signal and functions as an inhibitor of IL-1 action (J. Saklatvala et al., 1996). The two types of TNF receptor, p55 (type I) and p75 (type II) have different end effects; p75 mediates the proliferative actions of TNF- a while p55 receptor signals the inflammatory response and apoptosis (J. Saklatvala et al., 1996). Complex interactions between these different mediators produce intense pathophysiological modification, which eventually lead to diffuse tissue injury and ultimately sequential system failure (multiple organ dysfunc tion syndrome), which accounts for the majority of deaths among patients with sepsis, severe sepsis and septic shock (Beal Cerra, 1994). IL-1ß and TNF-a have a very short half life compared to IL-6 and therefore IL-6 is a very good indicator of cytokinemia. The initial studies of septic shock, showed a very strong positive correlation between IL-6 levels and fatal outcome (Casey L. Et al., 1993). NO is equally a very short lived molecule with an estimated in vivo half life of only 0.1 seconds hence again it is hard to measure its levels in order to detect the severity of cytokinemia hence the severity of sepsis or septic shock. There are several molecules that contribute to the pro and anti-inflammatory responses in septic shock (Table 4); however I shall only focus on a few due to the limited word allowance. In response to inflammatory agents in septic shock, the released cytokines (TNF-a, IL-1ß, and IFN- ?), bind to their specific receptors activating a protein kinase called tyrosine kinase leading to both the activation of the nuclear factor-kB (NF-?B) (a transcription factor) and the phosphorylation of intracellular protein (Gao et al., 2008). A precise mechanism by which these cytokines act was proposed by J. Saklatvala et al. in 1996 however this has yet to be confirmed. Nitric oxide producing cells contain I-?B which is an inhibitor of NF-?B. For the activation of NF-?B, proteolytic cleavage of I-?B from NF-?B is required which forms NF-?B. This biological change allows the activated NF-?B to translocate to the nucleus, where it binds to the promoter region of the iNOS gene inducing transcription. It has also been reported to induce other inflammatory agents, such as cytokines and leukocyte-endothelial adhesion molecules (Janssen-Heininger et al., 2000). Tyrosine kinase present inside the cell acts as a messenger molecule involved in the proteolytic cleavage of I-?B/NF-?B and hence in the activation of NF-?B and iNOS expression (Hecker M, et al., 1996). In septic shock, the translated products of iNOS mRNA subsequently assemble forming the iNOS protein which in turn causes local NO proliferation (Thiemermann, 1997). Fig 2 shows the signal transduction pathway of iNOS expression in response to inflammatory agents. The physiological role of iNOS is to enhance the formation of NO (due to iNOS activity), which in turn may contribute to either the pathophysiology of septic shock (clinbical symptoms) or the host defence (Reviewed in Gao et al., 2008). Fig 3 shows a simplified schematic of the Anti Inflammatory cascade in the context of septic shock. Excess NO produced by iNOS has been reported to both induce and inhibit NF-?B (Kalra et al., 2000; Umansky et al., 1998). In year 2000, it was proposed that low levels of NO may induce further NO production while high concentrations do the opposite exhibiting a feedback mechanisms that would oppose the over expression of genes regulated by NF-?B (Janssen-Heininger et al., 2000). In addition NO at high concentrations competes with O2 at the active site of NOS, thus providing a feedback mechanism of its own synthesis (Griscavage et al., 1995; Rengasamy Johns, 1993). Biological Synthesis of Nitric Oxide (Nitric Oxide Synthases) NOS structure and substrates for NO production: In mammals, NO is exclusively formed from the enzymatic oxidation of one terminal guanidino nitrogen of the amino acid L-arginine. When expressed in moles, this reaction utilizes 1 mol each of arginine and O2, and 1.5 mol of NADPH, yielding 1 mol of NO, 1 mol of L-citrulline and 1.5 mol of NADP (R.G. Knowles et al., 1994). The reaction sequence involves the generation of an Ng-hydroxy-L-arginine intermediate, followed by the oxidation of Ng-hydroxy-L-arginine in presence of molecular oxygen to form L-citrulline and NO (Dennis J. Stuehr et al., 1991 and R.G. Knowles et al., 1994). The enzymes that accelerate the reaction above are a family of relatively large heme proteins known as NO synthase (NOS) which resemble cytochrome P450 structurally (M. M. Chan et al., 2001 and Francois Feihl, 2001) (The general mechanism of NO production from NOS is illustrated in Fig 4). All members of this family share a similar homodimeric structure, where each monomer consists of a an oxygenase domain and a reductase domain, separated by a short amino acids (30aa) sequence for the attachment of the Ca2+-binding protein calmodulin. In addition to calmodulin attachment, enzymatic activity requires the presence of four cofactors: FAD, flavin mononucleotide (FMN), tetrahydrobiopterin (BH4), and heme (Francois Feihl, 2001). Fig 5 shows the general structure of the NOS enzymes. Nitric Oxide Synthase isoforms and their locus in the Human Body: There are three known isoforms of NOS, each the product of a different gene: neuronal NOS (nNOS or NOS-1), inducible NOS (iNOS or NOS-2), and endothelial NOS (eNOS or NOS-3). nNOS and eNOS were first described in rat cerebellum and bovine aortic endothelial cells, respectively, but their tissue distribution is far wider than suggested by their names. eNOS and nNOS are involved in regulating vascular tone (R.G. Knowles et al.,1992 and S. Moncada et al., 1991) and neurotransmission respectively, whereas iNOS is involved in the immune defence although it is expressed in many cell types following endotoxin or pro inflammatory cytokine treatment (R.G. Knowles et al., 1994). nNOS is typically expressed in skeletal muscle and myenteric plexuses. eNOS is ubiquitous in vascular endothelium, but may also be found in the kidney tubular epithelial cells, placenta (Forstermann et al., 1995), and neurons (Nathan Xie, 1994). In these tissues, the expression of nNOS and eNOS is constitutive, although it may be regulated (Michel Feron, 1997). For instance, the levels of transcript for eNOS in vascular endothelial cells is increased by shear stress (Topper et al., 1996; Uematsu et al., 1995) and exercise (Wang et al., 1997), reduced by inflammatory stimuli such as TNF-a (Nathan Xie, 1994) and variably affected by hypoxia (Le Cras et al., 1998; Toporsian et al., 2000). In the physiological state, the iNOS isoform is only present at a few locations, notably the respiratory epithelium, the gravid uterus (Nathan Xie, 1994), and perhaps the ileal mucosa (Hoffman et al., 1997). iNOS expression has been demonstrated in numerous cell types including macrophages, neutrop hils, vascular endothelial (Hoffmann et al., 1999), smooth muscle cells, endocardium, myocardium, fibroblast, mesangial cells, renal tubular epithelium (Kunz et al., 1994), neurons, hepatocytes, pancreatic islet cells and astrocytes (Nathan Xie, 1994). iNOS can be induced by a number factors including UV light; cyclic AMP-elevating agents; trauma; ozone and bacterial products described earlier (see section). On the other hand, many endogenous agents may oppose cytokine induction of iNOS. These include anti-inflammatory cytokines such as IL-10, chemokines such as monocyte chemoattractant protein-1 and growth factors such as tumor growth factor-ß (Forstermann et al., 1995). In all NOS isoforms, calmodulin binding is an absolutely vital for enzymatic activity. In the cases of eNOS and nNOS, this binding necessitates relatively high concentrations of Ca2+ (see Fig 7), in the range of 0.1-1 mM (Forstermann et al., 1995). In contrast, iNOS is able to bind calmodulin virtually independ ant of Ca2+ (Table 2). Therefore, once iNOS is expressed, NO synthesis may only be limited by the availability of substrates and cofactors (J. Stuehr, 1990). As NO produced from iNOS predominantly depends only on iNOS expression, it lasts much longer than NO formed from the other isoforms of NOS. In addition iNOS produces much higher concentrations of Ca2+ compared to the consecutive forms of NOS (Cobb et al., 1996). The production of NO by eNOS and nNOS, compared to iNOS, can be controlled relatively easily by decreasing or increasing intracellular Ca2+, whereas iNOS can only be controlled through transcription (Cobb et al., 1996). In most cell types iNOS protein levels are either very low or undetectable. However, stimulation of these cells by cytokines or growth factors, can lead to increased transcription of the iNOS gene, with subsequent production of NO. On the other hand, for the prevention of iNOS expression through endotoxins, TGF-ß (Szabo, 1995) and anti inflammatory gl ucocorticoids can be administered which lower the magnitude of vascular hyporeactivity. Glucocorticoids such as Dexamethasone inhibit iNOS activity by blocking arginine transport and inhibiting tetrahydrobiopterin biosynthesis (A.J.B. Brady et al., 1992 and Thiemermann C et al., 1993). Regulation of NO production In the normal as well as in extreme physiological states (e.g. during infection), nitric oxide is considered as one of the most important signalling molecules in vivo. It is however also highly reactive and highly diffusible due to it being a free radical (one unpaired electron) (see fig 8). It is therefore important that there is strict control and regulation of nitric oxide production. The synthesis of NO within cells can be regulated in several ways such as the cellular distribution of NOS, changes in NOS gene expression, enzymatic activation by phosphorylation and the presence of cellular inhibitors NOS activity. Intracellular distribution of NOS Nitric oxide is principally regulated through strict control over the location of NO production. The NOS isoforms can be targeted to different regions of the cell, where NO will be produced in close contact with its target proteins. The image below shows the distribution of iNOS (shown in green in image 1) and eNOS (shown in red) in a trophoblast cell. The nucleus is shown in blue. Co-localisation between iNOS and eNOS will show up as a yellow colour (Phil Dash, University of Reading). The image shows that eNOS and iNOS are fairly variably distributed inside the cell, with hardly any yellow colour suggesting very little overlap in their cellular distribution (Phil Dash, University of Reading).Although both iNOS and eNOS produce NO it is likely that their different cellular distribution will lead to NO interacting with different targets and therefore having different effects (Phil Dash, University of Reading). It is very likely that the distribution of NOS isoforms is an important mechanism for regulating when and where NO is produced. Therefore the current research on NOS mainly focuses on how endogenous signals trigger NOS transport and redistribution (Rahul S. Koti et al., 2005). Activation of NOS activity NOS enzyme synthesis is principally regulated by changes in intracellular calcium levels. The constitutive isoforms of NOS, (eNOS and nNOS) have shown to proliferate following increases in Ca2+, and therefore calmodulin levels, in the cell (Rameau et al., 2003). Additionally both nNOS and