Marketing Strategy Study Guide

MKT 850 Study Guide Chapter 5 * SWOT Analysis: * One of the most helpful apparatuses in investigating promoting information and data * Links company’s circumstance examination and improvement of showcasing plan * Uses organized data to reveal upper hands and guide choice of the vital focal point of the advertising technique. * Broken down into: * Strengths, Weaknesses, Opportunities and Threats * Productive SWOT (supervisor should†¦) : * Use a progression of SWOT investigations concentrating on explicit item/showcase mixes * Search for contenders both present and future Collaborate with other utilitarian zones by sharing data and viewpoints * Examine issues from the clients point of view by asking workers: * What do clients accept about us as an organization? * Which of our shortcomings convert into a diminished capacity to serve clients? * Looks for causes not qualities considering the organizations assets for each part * Separate inward and outside issues utilizing this key test: * Would this issue exist if the firm didn't exist? * If truly, issue delegated outer * Strengths and Weaknesses: Exist on account of assets by the firm, or because of the idea of key connections between the firm and its clients/representatives/outside associations * May be utilized into capacities (qualities) or survive (shortcomings) * Meaningful just when they help or frustrate the firm in fulfilling client needs * Opportunities and Threats: * Not potential showcasing activities. Issues/circumstances that happen in the firm’s outside situations. * Not disregarded as the firm becomes involved with creating qualities and capacities inspired by a paranoid fear of making an effective, yet inadequate association. Originate from changes in the serious, client, monetary, political/legitimate, innovative, and sociocultural situations. * SWOT Matrix: * Allows showcasing supervisor to picture the examination * Serves as an impetus to direct the formation of advertising tec hniques that will deliver wanted outcomes. * Allows administrator to perceive how qualities and openings may be associated with make capacities that are vital to addressing client needs * Assesses the extent and significance of every quality/frail/opp/danger. * Competitive Advantage: Capabilities in relations to those held by the opposition * Based on both inward and outer variables * Based on the real world and client observation * Based on the fundamental techniques of operational greatness, item authority, and client closeness. * Strategic Focus Establishment * Based on building up a general idea or model that controls the firm as it meshes different advertising components together into a sound technique * Tied to firm’s upper hand * Use consequences of SWOT as firm thinks about four bearings of vital endeavors: * Aggressiveness Diversification * Turnaround * Defensiveness * Ensures the firm doesn't step past center qualities to consider openings outside its capacities * V isualized using a methodology canvas where the objective is to build up a worth bend that is particular from the opposition * Downplay conventional industry serious factors for new methodologies * Lays basis for improvement of showcasing objectives and goal, interfaces SWOT results to the remainder of the promoting plan. * Marketing Goals: Broad, wanted achievements began as a rule terms. * Indicate the course the firm endeavors to move in, just as the arrangement of needs will use in assessing option and deciding. * Should be feasible, reasonable, inside steady, far reaching, and explain the jobs of all gatherings in the association. * Involves some level of immaterialness * Marketing Objectives: * Specific and quantitative benchmarks that can be utilized to measure progress toward the accomplishment of the advertising objectives * Should be feasible with sensible exertion Continuous or spasmodic relying upon how much they withdraw from present goals * Assigned to explicit territor ies, offices, or people who have the obligation to achieve them Chapter Six * Buyer Behavior in Consumer Markets: * Often nonsensical and flighty as shoppers state a certain something and do another * Progress through five phases: * Need Recognition * Information Search * Evaluation of Alternatives * Purchase Decision * Post Purchase Evaluation Don’t consistently follow these phases all together or may skip stages * May be portrayed by faithfulness where buyers basically buy a similar item that they purchased last time * Involves equal sequencing of exercises with finding the most reasonable trader. * Consider what item they need, and where to get it * Can happen if a customer is wildly faithful to a shipper * Can be influenced by: * Complexity of the buy and dynamic procedure * Demographics, Psychographics, and Sociocultural components * Social impacts: culture, social class, family, feeling pioneers, reference gatherings. Situational impacts: physical and spatial impacts, s ocial and individual impacts, time, buy task/utilization, buyer aura * Consumers Wants and Needs: * Shouldn’t characterize needs as necessities since everybody has an alternate point of view on what establishes a need * Needs happen when a shoppers current degree of fulfillment doesn’t equivalent their ideal level * Wants are purchasers want for a particular item that will fulfill a particular need * Firm should comprehend fundamental needs satisfied by its items. Permits firm to fragment showcases and make advertising programs that show needs into needs for their item * Most items are promoted based on needs not need satisfaction * Wants are not equivalent to request * Demand: happens when the buyers capacity and readiness to pay backs up a need for a particular item * Information Search: * Passive and Active: * Passive-purchaser become progressively mindful and open to data * Active-shopper connects increasingly forceful looking for data search * Depends on a few iss ues: Degree of hazard * Level of skill * Actual expense of search (time and cash) * Culminates in an evoked arrangement of reasonable purchasing options * Evaluation of Alternatives: * Translates needs into needs for explicit items or brands * Evaluate items as packs of qualities that have differing capacities to fulfill their necessities * Priority of every buyers decision standards can change * Want the item to be in the evoked arrangement of potential choices * Constantly help them to remember their organization and items * Purchase Stage: Intent to buy and the genuine demonstration of purchasing are unmistakable ideas * Key issues: * item accessibility: how simple is it to get the item where the shopper is * ownership utility: how simple is it to move proprietorship * Postpurchase Evaluation: * Outcome of purchasing process is connected to the improvement of long haul client connections. Intently follow customers’ reactions to screen execution and capacity to meet custome rs’ desires * Will encounter one expected results: Delight, fulfillment, disappointment, or subjective cacophony * Business Markets: * Purchase items for their utilization in their tasks, such as purchasing crude materials, purchasing office supplies, or renting vehicles * Consists of four kinds of purchasers: * Commercial markets * Reseller markets * Government markets * Institutional markets * Four one of a kind attributes not found in shopper markets: * The purchaser place: financial purchasers, specialized purchasers, and clients * Hard and delicate expenses are similarly significant Hard-fiscal cost or buy costs * Soft-personal time, opportunity costs, HR costs * Reciprocity: business purchasers and dealers frequently purchase items from one another * Mutual reliance: sole-source or constrained source purchasing makes both purchasing and selling firms commonly subordinate * Business Buying Process: * Sequence of Stages: * Problem Recognition * Development of item determi nations * Vendor recognizable proof and capability * Solicitation of proposition and offers * Vendor choice Order handling * Vendor execution survey * Can be influenced by a few elements including: ecological conditions, hierarchical elements, and relational/singular variables * Market Segmentation: procedure of isolating the all out market for a specific item or item class into generally homogeneous fragments or gatherings * Groups ought to have comparative individuals, yet bunches must be disparate from one another * Fundamental choice of whether to section at all Allows firms to be progressively fruitful because of the way that they can tailor items to address the issues of a specific market portion * Traditional market division approach: * Used effectively for quite a long time, not outdated, and are utilized by numerous individuals of today’s best firms * Can be utilized in mix with more up to date approaches by the firm, contingent upon the brand/item or market being re ferred to * Successful division: Must be recognizable and quantifiable * Substantial * Accessible * Responsive * Viable and maintainable * Avoid moral/legitimately touchy fragments * Avoid reasonable portions that don’t coordinate firm’s crucial Mass Marketing: no division and is focused on the complete market for an item * Undifferentiated methodology accept all clients have comparative needs/needs * Works best when requirements are moderately homogeneous Advantage-creation proficiency and lower showcasing costs * Disadvantage-dangerous on the grounds that a normalized item is powerless against contenders that offer particular items that better match customers’ needs * Differentiated Marketing: partitions the all out market into gatherings of clients having moderately homogenous requirements, endeavoring to build up a promoting program that interests to at least one of these gatherings * Necessary when client needs are comparable inside a solitary gathering, ho wever the necessities contrast across bunches * Two choices: * Multi-portion approach * Market fixation approach Niche Marketing: concentrating endeavors on one little, very much characterized

Life in times of Second World War Essay

I think it’s harder to live through a war for a common resident than a trooper. A fighter in the front line has little else to stress yet over the following fight joined with his own destiny. What’s progressively, a fighter consistently accepts that the ultimate result of the war can be impacted by his activities. In this way he has a feeling of interest and confirmation to the outcomes. Be that as it may, for a regular citizen, an individual disconnected from the field of activity, there is nothing to do except for to pause and expectation. Many would state this circumstance is far superior than to hazard life in the combat zone; in any case, my own experience says that the sentiment of inaction and defenselessness that comes being a regular citizen is stifling. There is nothing more discouraging than tuning in to war news while being not able to impact its result in any noteworthy manner. I was experiencing stomach ulcer when the war had begun and the military specialists had wouldn't acknowledge me in the administrations. It’s genuine that as a wartime non military personnel I effectively connected with myself in wellbeing establishments, where serving the injured gave a feeling of commitment to the war endeavors and belongingness to the contention that had so profoundly burdened the lives of more than 10 million individuals. The main period of the war Although we had proclaimed war upon Germany in ‘39, there was no inclination of expectation of war or sense danger anyplace in London. Nobody truly took the declaration any more genuine than a fight between two youngsters (Wilson, 41). I was an instructor in a boy’s school and the sparkling and energizing appearances of youngsters spoke to as though an energizing cricket coordinate was anticipating at that point. At that point everything out of nowhere changed. I heard with a developing feeling of danger the headways that bellicose German armed forces made through mainland Europe Wood and Depster, 155). It was inconceivable how nothing appeared to remain before them. Belgium, Poland, France, each falling like a pack of cards previously. And afterward the primary bomb struck London in September ‘40. So far I can review, there was no frenzy, however a bound feeling of assurance that we as a whole felt, anxious to complete our own obligations simultaneously (Fusell, 29). The nearby specialists had mentored us well on the utilization of gas covers and shelters in the midst of strikes. Power outages were regular occasion. At whatever point there was an assault by German warplanes, which was day by day, the whole city turned itself off, plunging everything in total obscurity. It was a remarkable encounter a feeling of rush joined with fear as our warplanes ascended high to battle the German planes. (Fusell, 15) I took cover in a huge dugout that was worked in the back park. Numerous individuals, with a nursery space in their home, had constructed Anderson cover and waited there. Many like me, pick the open haven. I don’t think about others, however simply staying there discreetly with such huge numbers of individuals around enlivened me with solace and security (Air Ministry, 16). Open sanctuaries were less sheltered obviously, and being of bigger measurements they were effectively inclined to assault. As it occurred, lamentably some of them were struck by bombs and numerous guiltless lives were lost (Fusell, 15). On the off chance that anything this further settled us to confront the flying German dangers. Each morning when I left the haven and traveled through roads of London, seething structures, broke vehicles and running ambulances met the sight. I realized individuals had kicked the bucket during the German assaults and it gave me a liable inclination, having endure the night when a considerable lot of individual residents proved unable. The bombarding went on for two entire months and consistently I followed a similar everyday practice of going through the night in obscurity, passed out asylum. After the finish of shelling by end of October, I thought maybe things would come back to regularity. I truly needed that. The scarred essence of London, the destruction of structures and lives lost filled me with restlessness. In any case, as news came pouring in of German advances and extension of war in Africa and Asia, I didn't perceive any conclusion to the contention (Wilson, 65). The every day life had out of nowhere changed its character. In right around a total inversion of the circumstance, the security, solace and simplicity of previous days were supplanted by a proceeded with desire to move quickly and miserliness that plagued the whole London Wood and Depster, 155). Gone were the times of day by day parties, week by week visits, ends of the week at nation houses, and the rich English way of life. I had by and by been just incidentally associated with these attractions, yet as I used to make a trip from my school to home at night, music and party were gotten notification from a significant number of the pretty lodges and houses-this was in the pre war day. It had all out of nowhere ceased to exist. A large portion of the men had left for war, and ladies had ventured out to fill the empty positions Wood and Depster, 155). Britain didn't deliver adequate amount of food to meet its own prerequisites and imported the majority of the food grains and things for its utilization (Wood and Depster, 155). Wartime conditions had seriously confined the food flexibly and we saw execution of proportioning framework, where food was assigned through family amount (Gorrora, 71). I was never a pig, however throughout the years, tea had gotten one of my every day prerequisites. With war, apportioning and amount, tea evaporated from the market. Different things of every day prerequisites sugar, hamburger, and milk additionally turned out to be incredibly rare. Nobody griped of the shortage, yet everybody felt its spot. After the London besieging I elected to join a crisis clinical camp, which acquired a steady commitment and activity my life. Be that as it may, it was not the kind of commitment I could love. Meeting seriously harmed men, ladies and kids, officers who had lost their appendages or were passing on because of illnesses, gangrene and lethal injuries was a terrible exercise for my will and individual endurance (Wilson, 71). Notwithstanding, in spite of my own feeling of misery, there was a rising expectation inside England that it would remain against the Axis forces and this expectation in itself was an inspiration enough for me to work in the emergency clinic day and night. There were numerous evenings in continuation when I scarcely shut my eyes for 60 minutes Our expectation and perseverance at long last took care of when following 5 years of gore, the war at long last finished. We were at that point arranged by the general news for this news, however the enormous help brought by even this realized data is unbelievable (Wilson, 101). It gave the idea that in the wake of being covered alive for a considerable length of time, I had by and by showed up on a superficial level, allowed to breath the natural air, allowed to see the sun, allowed to live once more. Reference Wilson, E. Perilous Sky: A Resource Guide to the Battle of Britain. Greenwood Press, 1995. 128 pgs. Wood, D. furthermore, Depster, D. D. The Narrow Margin: The Battle of Britain and the Rise of Air Power 1930-40. Hutchinson, 1961. 538 pgs. Air Ministry. The First Great Air Battle ever: The Battle of Britain, an Air Ministry Record of the Great Days from August eighth to October 31st, 1940. Nursery City Publishing, 1941. 56 pgs. Fussell, P. Wartime: Understanding and Behavior in the Second World WarBook; Oxford University Press, 1990. 330 pg Burdett, Gorrara, C and Peitch, H. 1999. European Memories of the Second World War. Berghahn Books, 1999. 338 pg

Marketing Management

Marketing Management Marketing Management Home›Marketing Posts›Marketing Management Marketing PostsMarketing practices over timeHuman behavior is viewed as being affected by multiple levels of influence. These levels of influence include intra-personal or interpersonal factors, individual factors, public policy factors, institutional or community factors, and organizational factors. Intra-personal factors include individual characteristics that influence behavior such as prior disposition, knowledge, attitudes, beliefs, and personality traits. Interpersonal factors refer to primary groups such as family, colleagues, and peers. The role of a primary school is to offer social distinctiveness support and meaning. Marketing strategies and performances depend on the culture inherent in a country. The same differs from one country to another. Countries where women’s major role is defined as home making, for example, are more often served by distribution systems that include bargaining.Arguing about the price of the products requires that considerable time be spent shopping. Where women are likely to have a career outside the household, time becomes more precious â€" which is a constraint on bargaining. In those cultures, fixed prices are more common (Williams and Curtis, 2005). Institutional factors are informal structures, policies, regulations, and rules, which may limit or promote suggested behaviors. Institutional procurement practices in general display characteristics that differentiate them from consumer markets. Hospitals, for example, would exhibit concentrated and direct purchasing of drugs from producers and inelastic demand once contracts are negotiated.These contracts would not be easily terminated. Community factors are social norms and networks, which exist as informal or formal among individual organizations and groups. For example, nutrition education and public awareness campaigns carried out by different social groups can promote healthy lifestyles that in turn influence the purchase of organic produce. Public policy refers to local state laws and policies that control or support practices and actions that are healthy, for disease prevention, early detection management and control.For example, the control of occupational exposure to carcinogens is a direct result of developments in public policy. This is an important step in primary cancer prevention and demonstrates that systematic regulatory control of the workplace can be an effective cancer prevention measure. This in turn affects tobacco-marketing practices. Marketing practice changes are also influenced by a diversity of other factors. Ecological or environmental regulatory bodies and processes, trading policies and funding and grants are key political factors. General taxation issues, interest and exchange rates and seasonality or weather issues form the body of economic factors that may influence change.Similarly, the advent of computers and the internet has considerably altered th e face of marketing. Nowadays, distributors and sellers can reach a mass market through online advertisements, shops, and email. Additionally, marketing research and intelligence can easily be catered by aggregating the number of visitors to any site as well as buyers of a product.Marketing SegmentationSome technology factors include research-funding, maturity of technology, innovation potential, intellectual property issues and progression of information and communication systems (Contento 2010). Marketing segmentation refers to the identification of one’s customers, bringing to them what they wish for, building strong relationships with co-marketing partners and communicating via highly targeted promotional media for example event sponsorships or interactive websites. Segmentation is the practice of partitioning markets into groups of prospective clientele with like needs, preferences and tastes. Segmentation efforts must be managed for them to be effective and ensure profitabil ity.It is impossible to pursue every market opportunity so managers must make strategic choices. There are many alternative methods for segmenting business markets. In outlining geographical segmentation, a medical instrumentation firm can obtain data from hospital associations’ directories to target hospitals by region and bed size. When factoring business demographics, a graphic supplies distributor can easily target advertising agencies by using firmographs.When featuring the products usage factor, markets can be segmented according to consumption levels of various user groups; heavy, medium or light. The best customers can be identified by several criteria. These include number of orders, unit sales, revenues, profitability and share of customer volume (Weinstein, 2004). The underlying rational of a mass marketing strategy is that everyone in the market wants the same product delivered, priced, and promoted in the same way. Alternatively, if there are differences within the ma rket, they are not usually significant enough to affect demand. They also do not merit being addressed by the organization with a different marketing mix strategy.Advantages in this type of marketing include elimination of extra costs that ensure larger production runs. Its limitations, however, underscore its limited usefulness. Different shopping patterns, income levels, and work habits require different pricing for certain services or products. This is well served by the segmentation strategy. In addition, a mass marketing strategy that tries to appeal to everyone leaves a company susceptible to having a segment of its customers won over by any other firm that more closely tailors its marketing mix to attract that particular subgroup.Client-Centered MarketingClient centered marketing is a core business process that makes an individual client or high potential prospect in a targeted industry; market niche the focus and beneficiary of specialized information, resources and experien ce. It encompasses selecting a targeted industry market niche for special attention as well as developing an insider’s understanding of it. It also involves positioning, promoting, and providing value adding solutions to selected needs of clients and high potential prospects in the niche. Finally, time, resources, and relationships available to the company are leveraged to secure success in the capturing of the target market.As the market changes from an orientation centered on product sales to one centered on the customer, direct marketing efforts to target profitable customers across the multiple channels, especially the internet, have resulted in reams of data waiting to be analyzed for enhancing future market efforts. Any market today, irrespective of size, can collect data on every customer transaction. These data are then stored in some format in a database for some future use such as financial tracking or inventory management purposes.BrandA brand is an icon or mark (logo) that helps distinguish one product from another. The brand represents the product. From the marketer’s point of view, it is the sum total of all user experiences with a specific service or product, building both repute and future expectations of benefit. Successful brand building involves paying constant attention to user enjoyment of a given product or service; setting sufficient budgets for marketing and evolving the brand overtime as markets and opinions change. Companies invest in building and marketing their brands for a number of reasons. These include increased recognition, establishing trust and building brand loyalty.Brand loyalty is achieved when clients stay faithful to a given brand and, whenever possible, take pains to continue their use of that brand. In the 21st century, the useful economic life of a brand cannot be defined in a pre-determined number of years. While most physical assets can be valued using models that use ten years or less to reflect their useful ec onomic life, brands have indefinite lives. The duration of a brand’s life depends on the readiness of consumers to buy the brand, pay the amount requested by the owner, and continue buying the brand into the future.This is consumer brand equity. It contributes to the ability of a company to earn profits in excess of those that would be earned by a normal company (Cant, Strydom, and Jooste, 2009).“THE LOST TRIBES OF RADIO SHACK: TINKERS SEARCH FOR A NEW               SPIRITUAL HOME”Andy Cohen bought the Radio Shack after years of being successful product manager companies of great worth. However, in recent times, he has obviously been by passed by trends. Radio shack has been forced to re- brand itself in an effort to attract new clientele with more sophisticated needs than the average Joe had in times gone by. New managers in the store have been uncomfortable with the increasing reliance on mobile technology to not only affect purchasing trends but in the acquisition of new cu stomers. It is obvious that they have been left behind in the move of trends from product-based marketing to service oriented marketing.The re-branding of itself to “the Shack” is hoped to alter the image of Radio Shack in the mind of the present day consumer. To this end, advertisements through the television and the internet have been employed. A dance contest was even featured yet little was garnered from these frantic efforts. A systematic study of trends in the market and how to achieve them by way of low cost methods might have achieved more change. Though successful in that it has survived bankruptcy, this has been achieved by cost cutting measures rather than success in garnering new customers.To survive, Radio Shack has now moved to the mass market to its direct loyal customer base-its community. This it has done rather than engage in the market segmentation strategy that would suit the pockets of a larger enterprise. Radio shack has obviously been relegated to near irr elevance by modern marketing trends. Faithful client Mike D’Alessio eschews the recent past when it was a force to be reckoned with. However, even he is quick to admit that that time has passed.

The Work For The Government Essay - 1449 Words

1.The author gives many reasons as to â€Å"why† work for the government. Choose 5 reasons given and explain what they are and whether or not they appeal to you. (3 pts) Here are five of the reasons the author gives for working in the government. Stable employment. This is one of the major perks of working for the government, mostly for the federal government. Government employees keep their jobs in many occasions until is their time for retirement. Even though is not something that happens to everybody, in cases where the government has reductions in personnel or change in departments their employees may go find a job in another agency or department. As many government employees that I know would say. â€Å"there’s nothing like knowing that your paycheck will be there every 1st and 15th of the month. Pay and benefits. As mention in the book, the pay government employees get is usually less than the one for employees in the private industry. Mostly in the management level, but the benefits given by the government are what makes up for the gap in payment. When taking the benefits under consideration, the government employee may earn more than people in the private sector. I used to be in the military and the pay was not that great, but the benefits make so much for it. If I ever consider working for the government, benefits would be one of the biggest factors for making that decision. Variety of Career Opportunities. There are many different agencies in the government, and theShow MoreRelatedGovernment Control Throughout Literary Works1486 Words   |  6 PagesGovernmental control surrounds society daily and has been around for centuries. Governments came around so that they could control others. It recurs throughout The Tragedy of Romeo and Juliet by William Shakespeare, as well as in The Count of Monte Cristo by Alexandre Dumas. Even in modern day, government control remains a significant part of life. For example, the SOPA bill arose in Congress when the need for anti-piracy protection became urgent or the USA admitting the Yemeni dictator into oneRead MoreHow does lobbying work in government1304 Words   |  6 Pages1. How does lobbying work in government? Lobbying is an enormous business. A lobbyist is an advocate who seek outs to influence members of the government (like members of Congress) to endorse legislation that would advantage their group. The lobbying occupation is a lawful and essential part of our democratic political procedure that is not extremely well implicit by the broad population. While the majority people think of lobbyists only as paid experts, there are as well a lot of volunteer lobbyistsRead MoreInformation of Government Agencies to Work For Essay2800 Words   |  12 Pages(national aeronautical and space administration). The administrator of NASA is Charles F. Bolden Jr. NASA’s vision is â€Å"to reach for new heights and reveal the unknown so that what we do and learn will benefit all humankind†(nasa.gov). Thousands of people work around the world to insure that NASA’s vision does come true. These people have been working at it for more than 50 years. NASA started back when President Dwi ght D. Eisenhower established NASA in response to the Soviet Union launching a satelliteRead MoreThe Constitution Set The Ground Work For The Federal Government1757 Words   |  8 PagesThe Constitution set the ground work for the federal government and the three branches government it is divided into. The philosophy behind the Constitution was create a government that was not too weak and not too strong but had equal power. The legislative, executive and judicial branches all serve a different purpose but play a very important role in the US government. The Judicial branch is the most important branch of government as it has the power to overrule unconstitutional laws and evaluateRead MoreElderly Care: Family and Government Should Work Together Essay1104 Words   |  5 Pagespeople live longer. As these groups grow old they become helpless, some are unable to work and while some fall sick to diseases like Alzheimer. The responsibility of taking care of them now either fall into the hands of their immediate family, and in some cases extended family and or the government depending on the culture. However, to make for a result oriented care the government and family needs to work together and culture can influence the commitment of family to the care of the elderlyRead MoreWhat Is The Necessity Of Government Financial Compensation For Womens Work In The Home1236 Words   |  5 PagesAnalysis of the Necessity of Governmental Financial Compensation for Women’s Work in the Home This sociological study will define the necessity of providing governmental financial compensation for women’s work in the home. Historically, the debate over the financial value of domestic labour has been an increasing problem in relation to gender struggles in the Canadian economy. Women/housewives have often been ignored for their work in the home due to the dominance of a patriarchal workforce. The problemRead MoreGovernment Agency Is Increased Work Load On The Staff And The Team Members1460 Words   |  6 PagesAnalysis of the Problem The problems that have been raised in the government agency are increased work load on the staff and the team members, which in turn has resulted in poor performance and late submissions of the work given. The work load has increased but there are no additional resources available for the current staff. Lack of equipment in an organization automatically leads to inefficiencies and diminished results, which automatically reduce the passion of the workers. Due to the workloadRead MoreThe Federal Government Should Work On Promoting Either Nuclear Or Solar Energy1227 Words   |  5 PagesSummary of Contentious Issues The federal government should work on promoting either nuclear or solar energy. Energy is important for survival on a daily basis. In fact, the development of any nation depends on the long-term availability and increase of clean and safe energy that also supports the environment. Currently, no energy source can be said to be sufficiently capable of meeting future needs that a nation requires. It is important therefore to promote any particular type of renewable energyRead MorePost Disaster Response for Hurricane Katrina Government preparation efforts had been in the works1500 Words   |  6 PagesPost Disaster Response for Hurricane Katrina Government preparation efforts had been in the works for years prior to Hurricane Katrina striking the Gulf Coast. In fact a recent as 2004 a hurricane drill was hosted by FEMA simulating a disaster event rivaling that of Hurricane Katrina including the evisceration of the city in also a similar manner. This drill, otherwise known as the â€Å"Hurricane Pam† drill, caused enough of an effect to get additional funding for preventative measures. GovernorRead MoreDaniel Shays Would you work for a government that expected you to put your life in jeopardy, did1000 Words   |  4 PagesDaniel Shays Would you work for a government that expected you to put your life in jeopardy, did not pay you for your service and then try to seize your house and property to settle your debts? This is exactly what Daniel Shays’ government tried to do to him after returning home injured during the Revolutionary War. So why did he choose the path and become a member of the military? He didn’t, he had little choice due to financial debts! He was like many other young Americans at the time; without

Who Is Irish By Gish Irish - 761 Words

Sakna vour ENG 125 Prof: Sept 27, 2017 Negative Attitudes Culture shock is a normal problem for every immigrant. When you move to live in the other country, you will have to learn about new people, new culture, new language, and environment. Some immigrants are adopted after they live in that culture for a while, but some are not because they preserve the own culture. So, they will have to face an issue of culture interacting. The story â€Å" Who is Irish?† by Gish Jen is a story that demonstrates the controversial conflict culture of a sixty-eight with her daughter and her granddaughter. The grandmother maintains her Chinese culture, and she doesn’t open her mind to other culture. The grandmother tries to raise her granddaughter with her†¦show more content†¦She always criticizes her son in law family and her granddaughter behavior. She criticizes the Shea family are lazy, not hard working. For example, in the story I just happen to mention about the Shea family, an interesting fact, four brothers in the familyâ⠂¬ ¦Ã¢â‚¬ ¦but every one of them is on welfare ( Jen 4). She is too much involved in other personal life. Moreover, She always criticizes her granddaughter so wild, stubborn, and or being like a beggar. For example But Sophie is wild, Sophie is not like my daughter Nathalia or like me†¦Ã¢â‚¬ ¦Sophie now is walking around with no shoes like a beggar(Jen 1, 8). Sophie is just a little girl, so she should not judge her that way. Also, it seems normal to her culture when the grandmother judges on someone, but it is so rude and of defensive in American culture. She would feel the same way if other people criticized her. So, judgment is another unappropriated behavior of grandmother. Lastly, a significant unappropriated behavior of grandmother is being racist. She always thinks that her culture and her group of people are superior to other culture. She is using skin color, the culture, and the place that they were born to describe people. She only thinks Chinese culture and skin a re the best. For example, in the short story My little brown granddaughter, she is so precious to me...I dont know how she comes out so brown (Jen 7). She seems so frustrated about Sophie brownShow MoreRelatedAnalysis Of Gish Jen s Who s Irish?893 Words   |  4 Pagesshort story Who s Irish?, by Gish Jen, the main character is a fierce and detriment old women who is nearing the end of the line when she can t handle her granddaughters behavior. while reading â€Å"Who’s Irish?† again I became interesting in knowing about how gender inequality in china has changed over the last several decades since the story was written, and wanting to narrow the topic I focused on inequality in education in China. Not many women were fierce and independent women who could make aRead MoreAnalysis Of Mohsin Hamid s The Reluctant Fundamentalist And Gish Jen s Short Story Who s Irish881 Words   |  4 Pagescome together, one often considers own culture is superior to another. This cla sh of culture can be arised from the cleavages of generation, language and identity for a person who may share the same race, nationality and social value. In Mohsin Hamid’s noval the Reluctant Fundamentalist and Gish Jen’s short story Who’s Irish?, narrate the voice of Eastern immigrants live at the intersection of two cultures, both primary characters (Changez and the Chinese grandmother) react to the cultural intersection/conflictRead More Generational Gaps And Conflicts Essay1177 Words   |  5 Pages In the short story Who’s Irish by Gish Jen and Everyday Use written by Alice Walker, both authors address generational conflicts between mothers and daughters, as well as struggles to coexist while living in very different cultural mindsets. The moral of both stories is that cross-cultural issues exist in every family tree and we often find comfort in unlikely places. While a mother may not agree with her daughter’s choices she never loses lov e, and while a daughter may not like decisions thatRead More Summary of Gish Jens Whos Irish Essay547 Words   |  3 PagesGish Jen’s â€Å"Who’s Irish† tells the story of a sixty-eight-year-old Chinese immigrant and her struggle to accept other cultures different from her own. The protagonist has been living in the United States for a while but she is still critical of other cultures and ethnicities, such as her son-in-law’s Irish family and the American values in which her daughter insists on applying while raising the protagonist’s granddaughter. The main character finds it very hard to accept the American way of discipliningRead MoreThe s Irish By Gish Jen And The Son From America By Isaacs Bashevis885 Words   |  4 Pagescultural difficulties. â€Å"One Out of Many† by V.S. Naipaul, Who’s Irish? By Gish Jen and â€Å"The son from America by Isaacs Bashevis Singer, are stories about different immigrants and how their life chan ged once they moved to the United State. From there we can see all the challenges they had to face in a strange environment where everything seems upside and no place of acceptance. â€Å"One Out of Many† by Naipaul is a story about a named Santosh who moved from Bombay to Washington. Santosh was really happy withRead MoreEssay about Ethnic Differences Across Generations979 Words   |  4 Pages Ethnic Differences Across Generations nbsp;nbsp;nbsp;nbsp;nbsp;Gish Jen’s â€Å"Who’s Irish?† explores a Chinese grandmother’s thoughts and beliefs about her ethnically integrated family. The grandmother tells the story as though she is looking back on past events and thinking about how they have affected her present life. As her tale begins, she identifies her granddaughter, Sophie, as a wild three-year-old (161). Perhaps the grandmother associates with Sophie’s strong will, because she revealsRead More Chinese and American Cultures Essay example4350 Words   |  18 PagesChinese and American Cultures Chinese-Americans authors Amy Tan and Gish Jen have both grappled with the idea of mixed identity in America. For them, a generational problem develops over time, and cultural displacement occurs as family lines expand. While this is not the problem in and of itself, indeed, it is natural for current culture to gain foothold over distant culture, it serves as the backdrop for the disorientation that occurs between generations. In their novels, Tan and Jen pinpointRead MoreWhos Irish Essay781 Words   |  4 PagesIn â€Å"Who’s Irish†, Gish Jen demonstrates a family that has Chinese root and American culture at the same time. The main character is a fierce grandmother who lives in with her daughter’s family, and then ironically forced to move out because of her improper behavior during she raises her granddaughter. The author uses some unpleasant language and contents to describe the situation, which are effectively demonstrate how difficult and how struggle for people who lives in the gap between two differentRead MoreCultural Norms About Parenting Practices984 Words   |  4 Pagesof origin and how they were raised. In general, a common theme that emerges across cultures is a desire for a child to be obedient, respectful, polite, honest, and successful especially in school. In the stories Two Kinds by Amy Tan and Who’s Irish by Gish Jen the concept of a good parent in an Asian orientated culture is highlighted. In addition, both stories illustrate the cultural division between an immigrant mother and her Asian-American daughter. Although the actions of these mothers are aRead MoreAchieving Gender Equality : Education1520 Words   |  7 PagesAchieving Gender Equality: Education in China In Gish Jen’s short story Who s Irish?, the main character is a determined Chinese grandmother who moved to America with her husband when she was a young woman, and now, in her old age, she is nearing her limit when she cannot handle her granddaughter s behavior and how she is being raised. The story was written in 1956 and while reading it a question of interest grew in knowing about gender inequality in China and if it has changed in the last several

Why D1 Athletes Should Be Paid Free Essays

Trying to Get That Paper According to the NCAA, student-athletes are students first and athletes second. However over the last decade there have been many questions raised about what the actual definition of what a student-athlete really is. This is because of the millions of dollars generated by institutions that broadcasting and promoting these â€Å"student-first† athletes. We will write a custom essay sample on Why D1 Athletes Should Be Paid or any similar topic only for you Order Now The main question that arises from this is should the NCAA and or institutions/ conferences be paying athletes for their services? By looking at the billions of dollars a year that the business of college sports generates just in television and radio time alone, indicates that student athletes should be paid. If these schools and the NCAA are making billions of dollars from college sports, then why shouldn’t the athletes get paid for doing what they do? After doing some research over a year ago and taking another look at this issue now, the question about paying college athletes has stayed the same. The debate whether to pay college athletes or not arose in the 1980s after Southern Methodist University was caught paying football players for their services. Upon discovery of these infractions, SMU was administered the â€Å"death penalty†, including loss of scholarships and no participation in bowl games for five years. The controversy surrounding paying college athletes seems to have risen from this unfortunate circumstance and has been cultivated into a huge social topic today. Following the SMU scandal in the late 1980s the NCAA rewrote their guidebook that describes an athlete’s role in an academic institution. According to the NCAA, â€Å"Student-athletes are students first and athletes second. They are not university employees who are paid for their labor† (NCAA. com). Looking at the arguments made by the NCAA, they make a valid point in showing how athletes are â€Å"compensated† for their participation in sports. According to the NCAA, â€Å"Many [athletes] receive athletics grants-in-aid that can be worth more than $100,000 (NCAA. om). There are many people who would agree with the NCAA in saying that the scholarships given to the student-athletes is enough â€Å"compensation† for the student-athletes to cover their costs of attending school. There are many other topics that all have a role in deciding whether or not to pay college athletes; mainly television, memorabilia sales, and individual endorsement deals. The quest ion itself hasn’t changed over the years; it’s the financial situation that college institutions and athletes now are exposed to that has changed. All seemed fine and well until, starting in the early 2000’s, large Division 1 sports conferences signed deals with large television networks, generating millions of dollars in revenue for the institutions who were a part of the conference. So the question arose again, should we pay college athletes? According to research done by the National College Players Association, â€Å"If allowed access to the fair market like the pros, the average FBS football and basketball player would be worth approximately $121,048 and $265,027 respectively (not counting individual commercial endorsement deals)† (NCPANOW. rg). People today are still opposed to paying college athletes, but the case for actually paying them grows stronger year after year. According to ESPN columnist Michael Wilbon, college football and basketball generate over 11 billion dollars in television revenue. He argues, â€Å"why not take 1. 3 billion dollars off the top and, invest it, and make it available for sti pends to college athletes? † (Wilbon). Another person in favor of paying college athletes is former Penn State basketball player Stephen Danley. In his interview with National Review reporter, Duncan Currie, he says that, â€Å"in certain programs players are even allowed to take enough credits to graduate in four years. If they [the colleges] want â€Å"student-athletes† then they should at least give them the financial means to return for an extra year to complete a degree after their playing days are over† (Currie). These two arguments not only show that there is in fact funding to pay these athletes, but that scholarships don’t cover the actual amount of time it takes for a student to finish his/ her degree. So why not help them out financially and allow them to finish? Looking at the large amounts of money going to conferences and universities due to the profits of college sports, it’s easy to see where the debate about paying college athletes comes from. This isn’t a discussion of moral issue or ethical debate; rather, this is simply an issue of looking at the numbers generated and whether or not to pay these athletes for benefiting their schools in popularity and financial gains. So after looking at everything that encompasses college sports, the debate continues; should college athletes be paid? How to cite Why D1 Athletes Should Be Paid, Essay examples

Death of a Salesman, written in 1949 by American p Essay Example For Students

Death of a Salesman, written in 1949 by American p Essay laywright Arthur Miller, illustrates the destructive compulsion of a man to attain a success far beyond his reach. This is accomplished through the portrayal of Willy Loman, the plays central character. Willy Loman is a pathetic character because he does not hold any possibility of victory. Unrealistic dreams which are the product of a refusal to honestly acknowledge his abilities deter any triumph that Willy may have the ability to achieve.Throughout the play Willy Loman surrounds himself with an obvious air of insecurity and confusion. His lack of confidence and uncertainty in what he wants are qualities which prevent him from achieving his dream. Willy shows this weakness while observing himself in a mirror. He focuses completely on what he deems as negative qualities in his personality and physical appearance. In talking with his brother he reveals his insecurity by mentioning that he feels kind of temporar!y (pg. 51). Although Willy has chosen to pursue success as a salesman he demonstrates confusion by continually contradicting that choice. Barclay W. Bates (1983) clarifies this in saying that Willy resents the encroachments, such as the loss of fresh air and fertile land, increased population and, most significantly, the competition which have been spawned by the very business community he has opted to be a member of (Koon, pg. 61). It is impractical to assume that Willy Loman can be victorious in a career that he does not seem comfortable in or completely dedicated to. His attempts make him pathetic because they are at the expense of confidence that he may receive from another field of work.Willy Lomans false pride is another factor that contributes to his pursuit of a prosperity which is unobtainable to him as a salesman. This attribute is apparent in him when his mind journeys back to the day he turned down his brothers offer to battle for riches in the Alaskan timbe!rlands. Willys most enthusiastic moments in the play come in directing the rebuilding of the front stoop, teaching his sons to polish the car and in talking with Charley of the ceiling he put up in the living-room. These instances make it obvious that his true talents and joys lie in working with his hands. He is unable to go with his brother and put his skills to use because he has given his family the impression that he is greatly excelling in his career. He is unable to leave behind such great success as a salesman for uncertainty in the woods without admitting his true position and suffering the humiliation of his lies. Willy is ready to avoid that embarrassment at the cost of happiness so that his familys praise for him may continue to remain active. Willys false sense of pride also compels him to repeatedly refuse accepting the job offered to him by Charley, his friend and neighbor. Although he needs the money, Willy finds himself incapable of working for someon!e who is the success he himself only pretends to be. It is also that same false pride which brings him to degrade himself by borrowing money from Charley so that he can keep his stature intact with his family. What Willy Loman views as pride is, in reality, his self-deprivation. By ignoring what he is best fitted to do Willy does not allow himself happiness or the opportunity for triumph. This makes him a pathetic character.VWilly Loman cannot be victorious in achieving success because he does not have the aptitude to be a salesman or the capacity to be a good father. His jokes and much too talkative nature demonstrate his inability to do his job productively. .u8fc17883e964d5f0ecfd0c5997be35c5 , .u8fc17883e964d5f0ecfd0c5997be35c5 .postImageUrl , .u8fc17883e964d5f0ecfd0c5997be35c5 .centered-text-area { min-height: 80px; position: relative; } .u8fc17883e964d5f0ecfd0c5997be35c5 , .u8fc17883e964d5f0ecfd0c5997be35c5:hover , .u8fc17883e964d5f0ecfd0c5997be35c5:visited , .u8fc17883e964d5f0ecfd0c5997be35c5:active { border:0!important; } .u8fc17883e964d5f0ecfd0c5997be35c5 .clearfix:after { content: ""; display: table; clear: both; } .u8fc17883e964d5f0ecfd0c5997be35c5 { display: block; transition: background-color 250ms; webkit-transition: background-color 250ms; width: 100%; opacity: 1; transition: opacity 250ms; webkit-transition: opacity 250ms; background-color: #95A5A6; } .u8fc17883e964d5f0ecfd0c5997be35c5:active , .u8fc17883e964d5f0ecfd0c5997be35c5:hover { opacity: 1; transition: opacity 250ms; webkit-transition: opacity 250ms; background-color: #2C3E50; } .u8fc17883e964d5f0ecfd0c5997be35c5 .centered-text-area { width: 100%; position: relative ; } .u8fc17883e964d5f0ecfd0c5997be35c5 .ctaText { border-bottom: 0 solid #fff; color: #2980B9; font-size: 16px; font-weight: bold; margin: 0; padding: 0; text-decoration: underline; } .u8fc17883e964d5f0ecfd0c5997be35c5 .postTitle { color: #FFFFFF; font-size: 16px; font-weight: 600; margin: 0; padding: 0; width: 100%; } .u8fc17883e964d5f0ecfd0c5997be35c5 .ctaButton { background-color: #7F8C8D!important; color: #2980B9; border: none; border-radius: 3px; box-shadow: none; font-size: 14px; font-weight: bold; line-height: 26px; moz-border-radius: 3px; text-align: center; text-decoration: none; text-shadow: none; width: 80px; min-height: 80px; background: url(https://artscolumbia.org/wp-content/plugins/intelly-related-posts/assets/images/simple-arrow.png)no-repeat; position: absolute; right: 0; top: 0; } .u8fc17883e964d5f0ecfd0c5997be35c5:hover .ctaButton { background-color: #34495E!important; } .u8fc17883e964d5f0ecfd0c5997be35c5 .centered-text { display: table; height: 80px; padding-left : 18px; top: 0; } .u8fc17883e964d5f0ecfd0c5997be35c5 .u8fc17883e964d5f0ecfd0c5997be35c5-content { display: table-cell; margin: 0; padding: 0; padding-right: 108px; position: relative; vertical-align: middle; width: 100%; } .u8fc17883e964d5f0ecfd0c5997be35c5:after { content: ""; display: block; clear: both; } READ: Martin Luther King Jr. Essay His exaggerated claims of past profit and deals made with Howards father are not able to get him a position in New York because he has long been insignificant to the Wagner Company. He was placed on commission like an inexperienced newcomer to the industry on account of interference in his job productivity: You didnt crack up again, did you? (pg. 79). Willy is unable to keep his business obligations. He displays this irresponsibility when he fails to make a sales trip to Boston and, as a result, he is fired. Since his own father was not present throughout his life to act as an example, Willy Loman seeks guidance from his brother, who pays little interest to him or his wife and children, on how he should parent. Willy, in choosin!g one son over the other, makes his greatest mistake as a father. He ignores Happy, his younger son, in favour of the athletic Biff. The consequence of this type of parenting is the inheritance, by Happy, of the same desperate need for recognition that Willy possesses. Willy has failed Happy because his son is now obsessed with losing weight, is a proficient liar, and lacks respect for others. Most importantly, as showcased in the restaurant scene, Willys parenting has left Happy easily able reject him as his father when it is convenient for him: No, thats not my father. Hes just a guy (pg. 115). Willy shows that he is emotionally immature by allowing a football game to become much more important than his sons studies. This leads Biff to ignore his education and trivialize his future. Willy places great expectations upon Biff by way of always insisting that his eldest son will succeed. He does not allow his son to be anything other than what he wishes because h!e is attempting to live success through him. He shows disregard for Biff and reveals a selfish nature in not supporting the career paths that his son has chosen in the past. At the discovery of his infidelity, Willy does not try to show his son affection and help his son come to terms with the extramarital affair, instead, he never speaks of it again and leaves his son with the painful secret. Throughout the play Willy Loman does not obtain the skills required to be a successful salesman or father. Pathetically, he does not realize the limits of his capabilities and is, therefore, unable to assess realistic possibilities of victory. Victory for Willy Loman is overshadowed by his distorted view of how to attain success. Willy believes that you must start big and youll end big (pg. 64). He does not seem to understand that, before a person is able to climb their way to the top, they must first create the rungs on the ladder which reaches to success and that this must be !done through gaining working experience from the bottom. Willy proceeds through the play trying to sell himself and his image much more than the products he is peddling because of the ideology that they are his key to success. Brain Parker (1969) explains this in saying that: Be liked and you will never want, Willy advises his sons; and his famous distinction between being liked and being well liked seems to rest on whether or not the liking can be exploited for practical ends. Such using of friendliness falsifies it and invokes a law of diminishing returns, as Willys lonely funeral shows. (Corrigan, pg. 103) Suicide is Willys final attempt at gaining success. He clings to the idea that if his son is successful then he, in return, is also a success. The money from his $20,000 life insurance plan would allow Biff the ability to finally be as great as Willy has expected him to be. .uf07b9ea124d7123f09a7ebe56058f837 , .uf07b9ea124d7123f09a7ebe56058f837 .postImageUrl , .uf07b9ea124d7123f09a7ebe56058f837 .centered-text-area { min-height: 80px; position: relative; } .uf07b9ea124d7123f09a7ebe56058f837 , .uf07b9ea124d7123f09a7ebe56058f837:hover , .uf07b9ea124d7123f09a7ebe56058f837:visited , .uf07b9ea124d7123f09a7ebe56058f837:active { border:0!important; } .uf07b9ea124d7123f09a7ebe56058f837 .clearfix:after { content: ""; display: table; clear: both; } .uf07b9ea124d7123f09a7ebe56058f837 { display: block; transition: background-color 250ms; webkit-transition: background-color 250ms; width: 100%; opacity: 1; transition: opacity 250ms; webkit-transition: opacity 250ms; background-color: #95A5A6; } .uf07b9ea124d7123f09a7ebe56058f837:active , .uf07b9ea124d7123f09a7ebe56058f837:hover { opacity: 1; transition: opacity 250ms; webkit-transition: opacity 250ms; background-color: #2C3E50; } .uf07b9ea124d7123f09a7ebe56058f837 .centered-text-area { width: 100%; position: relative ; } .uf07b9ea124d7123f09a7ebe56058f837 .ctaText { border-bottom: 0 solid #fff; color: #2980B9; font-size: 16px; font-weight: bold; margin: 0; padding: 0; text-decoration: underline; } .uf07b9ea124d7123f09a7ebe56058f837 .postTitle { color: #FFFFFF; font-size: 16px; font-weight: 600; margin: 0; padding: 0; width: 100%; } .uf07b9ea124d7123f09a7ebe56058f837 .ctaButton { background-color: #7F8C8D!important; color: #2980B9; border: none; border-radius: 3px; box-shadow: none; font-size: 14px; font-weight: bold; line-height: 26px; moz-border-radius: 3px; text-align: center; text-decoration: none; text-shadow: none; width: 80px; min-height: 80px; background: url(https://artscolumbia.org/wp-content/plugins/intelly-related-posts/assets/images/simple-arrow.png)no-repeat; position: absolute; right: 0; top: 0; } .uf07b9ea124d7123f09a7ebe56058f837:hover .ctaButton { background-color: #34495E!important; } .uf07b9ea124d7123f09a7ebe56058f837 .centered-text { display: table; height: 80px; padding-left : 18px; top: 0; } .uf07b9ea124d7123f09a7ebe56058f837 .uf07b9ea124d7123f09a7ebe56058f837-content { display: table-cell; margin: 0; padding: 0; padding-right: 108px; position: relative; vertical-align: middle; width: 100%; } .uf07b9ea124d7123f09a7ebe56058f837:after { content: ""; display: block; clear: both; } READ: Support Death Penalty Essay He holds the belief that his son will worship (him) for it (pg. 135) because the p!ossibility of true success will come into existence. Willy, shows irresponsibility in bypassing all thought of the trauma and hurt his family may experience as a result of his suicide. Willys illogical definition of success causes him to wander through life trying to achieve the impossible. This makes him a pathetic character because there is never any chance for him to rise above and become victorious.In Death of a Salesman, Arthur Miller gives his readers the opportunity to delve into the mind of Willy Loman and come away with an evaluation of their own definitions of success and victory and the destruction that they may hold. For Willy it is the refusal to honestly evaluate his abilities and limitations that makes him a pathetic character by stripping away any possibility of success. Perhaps others can use Willys example to avoid the unhappiness that he experienced throughout his life.

The True Tragic Hero in Antigone Essay Example For Students

The True Tragic Hero in Antigone Essay There is still a great debate on who is, in fact, the true tragic hero in Sophocles Antigone. Many hold that it must be Antigone, herself; after all, the play does bear her name. But in actuality, Creon, not Antigone, is the rue tragic hero. In order to determine whether or not Creon is the true tragic hero, one will first have to answer the question, What is a tragic hero? Aristotle, when discussing the nature of such a hero in his theory of drama, states that such a hero is neither purely innocent nor purely evil. This person is usually born high in the ranks of society and must also possess a tragic flaw, which originates from within and usually manifests itself through poor judgment and/or extreme arrogance. We will write a custom essay on The True Tragic Hero in Antigone specifically for you for only $16.38 $13.9/page Order now The tragic flaw also dooms the character to a ruinous end. Creon, as king of Thebes, is at the top of the social ladder. He thus already meets one of Aristotles chief criteria. Yet, not only is he king, he is also human and possesses frailties which qualify him to make serious mistakes and he possesses talents which allow him also to excel. Hence, Creon is neither overly good nor bad. It is also written that the tragic heros actions may determine the fates of one or more characters within the tragedy. Appropriately, Creons station as king place shim in a position of great power, influence and responsibility. The extent of this power was quite evident when he sentenced Antigone to death for disobeying his proclamation. Now we come to what, if anything, is the single most important component of being a tragic hero. Here we have the tragic flaw. Creons tragic flaw was his hubris or his pride and arrogance in the face of divine powers. His downfall began when he denied the basic divine right of burial to Polyneices and was cemented when he condemned Antigone for her opposition to his law. When one closely examines Antigones reasons for burying her brother, it becomes clear that she was simply demonstrating her love, honor, and loyalty to her family. However, the reason that Creon is angered is that he feels injured and insulted that Antigone flagrantly and publicly disobeyed him. He was additionally inflamed that she was his niece and betrothed to his son, Haemon. Historically, when a mans authority is threatened, especially by a woman, he ego is irreparably damaged. Thus if one must follow Aristotelian theory, the true tragic hero can only be Creon and not, as many continue to hold, Antigone. .

A Project work of Business Studies On Various Level Of Management Essa

A Project work of Business Studies On Various Level Of Management Essa National College of Computer Studies Paknajol, Kathmandu A Project work of Business Studies On Various Level Of Management Submitted by: Submitted to: Mr. Aashish Regmi Grade: XII L Lecturer Registration no. :NCCSHSS3672 Business Studies Recommendation This is to certify that the project report Submitted by Entitled Various Level of Management Has been prepared as approved for by this department. This field assignment is forwarded for examination. Mr. Aashish Regmi, Mrs. Anuradha Chaudhary, Lecturer HOD Business studies Business studies Mr. Shiva Krishna Dangol Programme Coordinator Bibliography Asmita Books Publisher and Distributer(P)Ltd. Bing.com http://google.com ABBERVIATION HOD Head Of Department Fig. Figure No. Number S. No Serial Number W.W.W World Wide Web ACKNOWLEDGEMENT I take this opportunity to acknowledge my heartfelt gratitude to my supervisor Mr. Aashish Regmi for his valuable guidance, constant encouragement and inspiration at every stage in my research work .It is no exaggeration to state without his guidance, suggestions and co-operation this study would not have got the shape it has. My sincere thanks and gratitude to the Head of Department Mrs. Anuradha Chaudhari .I also express my special thanks to Mr. Shiva Krishna Dangol , the program co-ordinator. Above all my special mention to our college National College of Computer Science. MANISH MAHARJAN List of Figure Fig. NoTitlePage no 1.1Managerial Level2 2.1Hierarchy In Kathmandu Nursing College7 Table of content Content page no. COVERPAGE RECOMMENDATION ACKNOWLEDGEMENT ABBREVIATION LIST OF FIGURE 1. INTRODUCTION 1-6 1.1 Background of the study 1 1.2 Statement of the problem 4 1.3 Objectives of the study 4 1.4 Significance of the study 5 1.5 limitations of the study 5 1.6 Research and Methodology 5 1.7 Organization of study 6 2. DATA PRESENTATION AND ANALYSIS 7-11 2.1 Hierarchy In Kathmandu Nursing College 7 2.2 Function of various level of management in Kathmandu Nursing College 8 2.3 Introduction to the human resource according to hierarchy 9 3. SUMMARY, CONCLUSION AND RECOMMENDATION 12-13 3.1 Summary 12 3.2 Conclusion 12 3.3 Recommendation and conclusion 13 BIBLIOGRAPHY APPENDIX APPENDIX

A+ Essay Example | Topics and Well Written Essays - 750 words

A+ - Essay Example Washington was an indefatigable actor who seemed to have lived the life of Boone himself, having the vitality of a Black man who was trying to fight for his rights and the rights of his fellowmen during the time of the busing system. Will Patton, on the other hand who played the role of Bill Yoast, the White American who coached along with Boone, was quite the opposite. His part seemed boring that if he were given longer parts in the movie, the story would have been a bore. Although he is a good actor himself, Patton’s soft voice and sometimes timid manners can make his parts monotonous. On a general note, the performance of the actor is worthy of an acclamation despite his serious role which probably influenced his mood in the movie. The Titans, the football team coached by the two aforementioned characters, portrayed different personalities, completing an exciting team of young people. Ryan Hurst who played the role of Gerry Bertier, the team’s captain played his role well, as he showed how the player bloomed from a self-centered, bigoted racist to a leader who valued his team’s attitude rather than race and status. His Black counterpart Wood Harris, who played the role of Julius Campbell, gave an equally highly rated performance. He had the same dynamic exuberance as Hurst that they shared together in bringing to life their respective roles. Both actors showed their emotions unrestrainedly, making their performances realistic and moving. The friendship that developed between the two characters was beautifully pictured through the emotions, conversations and naturally executed performances of the actors. Adding to the exciting and smooth flow of the story were the contributions of other actors who played the roles of other football players in the team. The different characterizations first of all, showed the many variations of characters, attitudes, beliefs and perspectives of people, which in real life; make living more beautiful,

Telephony Application and VoIP (voice over Internet Protocol Dissertation

Telephony Application and VoIP (voice over Internet Protocol - Dissertation Example Although VoIP has been commendable in replacing PSTN, its application is not without drawbacks based on security and privacy of voice call information and impacts on quality of service. This paper evaluates and explains VoIP in detail in order to understand its functions, advantages, disadvantages, VoIP protocols and, best protocols for VoIP application. The research reveals Session Initiation Protocol or SIP as the best protocol given that it is easier to secure and sustain the quality of VoIP service. Acknowledgements First and foremost, I thank my parents for their support in my pursuit of a college education. I am grateful for their unfading support financially and emotionally. I also thank my instructor, who since I decided on this topic, has been a great source of encouragement, supervision, and academic counseling. Without your sincere support, the completion of this paper would not have been feasible. I thank you once again. I also thank my classmate and friend Yasir who has been of much appreciate assistance in ensuring that I intensely research the topic and obtain detailed relevant material for use in this paper. My gratitude to you is beyond words. Finally, I thank everyone, who in any little way has assisted me in research, drafting the manuscript and whose support has remained untainted throughout the process. I thank you all and many blessings. Table of Contents Acknowledgements 3 Chapter One 6 Introduction to the Problem 6 Technology is advancing every day; included in that technological advancement is the improvement of telephone capabilities. While most are familiar with modern cell phone and smart phone technology, voice over internet protocol, or VoIP, is also a technological improvement, with regards to telephoning that should be considered. 6 Traditional telephony, or telephone technology, according to Meggelen, Smith and Madsen is the technology associated with the transmission of voice, fax, video or other form of information, electronic ally (2009). Such transfer involves parties located long distances apart and who are using systems originally linked with telephone. A telephone device is characterized by a transmitter or speaker on one side and a receiver on the other. The telephone science involves translation of sound or voice signal into electrical signals then transmitting them and translating them into sound signal at the destination. In the modern world, Meggelen, Smith and Madsen, point out that computer hardware and software assumes the roles that telephones used to (2009). Commendable changes in telephony were achieved by the arrival of computers, transmission of digital information over telephone systems and utilization of radio for transmission of telephone signals. 6 Internet telephony is the utilization of internet infrastructure and related technology instead of traditional telephone infrastructure to exchange voice, sound or other information transferable through telephone (MacKnight, Lehr & Clark, 2001). With internet telephony, telephone access is affordable at local connection rates. As a result, any long distance or international calls are much less expensive compared to the traditional call set up (Rouse, 2008). 6 The inception of the internet has led to the development of several new services, three

Effect of H1N1 Swine Virus on Humans

Effect of H1N1 Swine Virus on Humans How does the new H1N1 swine virus infect humans compared to the common influenza virus? SUMMARY Pandemic influenza viruses cause significant mortality in humans. In the 20th century, there are 3 influenza viruses which caused major pandemics: the 1918 H1N1 virus, the 1957 H2N2 virus, and the 1968 H3N2 virus. All three aforementioned pandemics were caused by viruses containing human adapted PB2 genes. In March and early April 2009, a new swine-origin influenza A (H1N1) virus (S-OIV) emerged in Mexico and the United States. During the first few weeks of strain surveillance, the virus spread worldwide to many countries by human-to-human transmission (and perhaps due to the airline travel). In 2 months time, 33 countries had officially reported 5.728 cases resulting in 61 deaths, and by June 2009 WHO reported 30 000 confirmed cases in 74 countries. On June 11 of 2009, this led the World Health Organization (WHO) to raise its pandemic alert to level 5 (Human-to-human spread of the virus into at least 2 countries in 1 WHO region) of 6 (Human-to-human spread of the virus into at least 1 other country in a different WHO region in addition to phase 5 criteria). According to the sayings of Smith et al. (2009), this virus had the potential to develop into the first influenza pandemic of the twenty-first century. In the early summer of 2009, the causes of the human infection and influenza spread among humans had still remained unknown although many publications of that period tried to elucidate this influenza outburst. For example, according to the sayings of Palese, the new H1N1 could also die out entirely. â€Å"Theres a 50-50 chance it will continue to circulate†, he predicts. Conclusively, in that early period, the fuzziness of the data about this new viruss behaviour led scientists only to speculate using past data. Today the 2009 H1N1 virus has ultimately created the first influenza pandemic, has disproportionately affected the younger populations (which perhaps reflects the protection in the elderly due to their exposure to H1N1 strains before 1957), bu t turned out to be not highly pathogenic because the majority of cases of 2009 influenza A H1N1 are mild. Genomic analysis of the 2009 influenza A (H1N1) virus in humans indicates that it is closely related to common reassortant swine influenza A viruses isolated in North America, Europe, and Asia. Therefore, it contains a combination of swine, avian, and human influenza virus genes. More studies need be conducted to identify the unrecognized molecular markers for the ability of S-OIV A (2009 H1N1) to replicate and be transmitted in humans. As a result these additional studies would help us to determine the mechanism by which an animal influenza A virus crossed the species barrier to infect humans. Additionally, these molecular determinants can be used to predict viral virulence and pathogenicity for diagnosis. 1. LITERATURE REVIEW 1.1. Introduction â€Å"Swine flu† †influenza A [Family Orthomyxoviridae (like influenza B and C viruses), Genus Influenzavirus A] is currently the greatest pandemic disease threat to humankind (Salomon and Webster, 2009). The incidence and spread in humans of the â€Å"swine flu† influenza A virus has raised global concerns regarding its virulence and initially regarding its pandemic potential. The main cause of the â€Å"swine flu† has been identified to be the human infection by influenza A viruses of a new H1N1 (hemagglutinin 1, neuraminidase 1) subtype, or â€Å"2009 H1N1 strain† (Soundararajan et al., 2009) that contains genes closely related to swine influenza (SI) [also called swine flu, hog flu and pig flu]. Thus, the strains of virus that cause the annual seasonal flu are different than the new swine flu viruses that emerged in the spring of 2009. Consequently, as it will be analyzed in the subsequent chapters, the new swine flu virus has a unique combinatio n of gene segments from many different sources (a combination that has not been previously reported among swine or human influenza viruses) and specifically is thought to be a mutation of four known strains of the influenza A virus, subtype H1N1: 1. one endemic in (normally infecting) humans, 2. one endemic in birds, 3. and two endemic in pigs (swine). According to Yoon and Janke (2002), the constant evolution of influenza A viruses through mutation and reassortment present a complex and dynamic picture which is to be unfolded in the remaining Literature Review section more specifically for the H1N1 2009 virus. 1.2. Influenza Influenza is historically an ancient disease of global dimension that causes annual epidemics and, at irregular intervals, pandemics. Influenza is an infection of the respiratory tract caused by the influenza virus (see  § 1.3). When compared with the majority of other viral respiratory infections (such as the common cold), the infection by influenza often causes a more severe illness (Smith, 2003). Influenza-like illness (ILI) is defined by the CDC (Centers for Disease Control and Prevention) as fever (with temperature above 37,8 °C) and either cough or some throat in the absence of any other known cause. According to Webster (1999), influenza is the paradigm of a viral disease in which the continued evolution of the virus is of paramount importance for annual epidemics and occasional pandemics of disease in humans which is attributed to the fact that the H1N1 virus does not fit to the strict definition of a new subtype for which most of the population has not any experience of previous infection (Sullivan et al, 2010) as it is justified later in this Literatute Review section ( § 1.8). Influenza is transmitted by inhalation of microdroplets (because the transmission via large-particle droplets requires close contact which is attributed to the fact that these large-particle droplets cannot remain suspended in the air for a long period of time) of respiratory secretions, often expelled by coughing or sneezing, that contain the virus or from other bodily fluids (such as fomites, diarrheal stool etc.). The incubation period is between 1 to 5 days. Symptoms typically include fever, headache, malaise, myalgia, cough, nasal discharge, and sore throat. In severe cases of influenza, a secondary bacterial pneumonia can lead to the death of a patient (Suguitan and Subbarao, 2007). Vaccination and antiviral treatment constitute the two major options for controlling influenza and are the most effective means of preventing influenza virus infection and further transmission in humans. 1.2.1. Pandemic Influenza An influenza pandemic is a large-scale global outbreak of the disease, whereas an epidemic is considered more sporadic and localized. The aforementioned (in the Summary section) situation of pandemic influenza occurs when a previously circulated human influenza A virus [although all the three types (A, B, and C) of influenza viruses can infect humans)] acquires novel antigenic determinants from an animal-origin influenza virus and now can infect and propagate in humans in the absence of any pre-existing immunity (see  § 1.7 for details). Several influenza subtypes have infected humans. Historical accounts led us to consider that an average of three influenza pandemics have occurred each century, at intervals ranging from 10 to 50 years (Garcia-Sastre, 2005). The three influenza pandemics which occurred in the previous (20th) century are: 1. The â€Å"Spanish† influenza pandemic of 1918 (H1N1 subtype), 2. The 1957 â€Å"Asian flu† (H2N2), and 3. The 1968 ‘‘Hong Kong flu (H3N2). These pandemics resulted in high morbidity, death, and also considerable social and economic disruption. They provide health authorities information on which to base preparations for a future pandemic.The first influenza pandemic of the 21st century, due to a new strain of A(H1N1) virus, was declared on 11 June 2009 by the Director-General of the World Health Organization (WHO) [Collin et al., 2009] by raising the H1N1 flu virus pandemic alert level to phase 6 as it was mentioned in the Summary section. Although influenza B viruses do not cause pandemics, during some epidemic years they have caused more significant mortality and morbidity than influenza A viruses (FLUAV) [Garcia-Sastre, 2005]. 1.3. Influenza Virus It was already mentioned that influenza viruses are divided into three types designated A, B, and C (according to the antigenic differences of their internal structural components as it is discussed below in the current chapter). Influenza types A and B are responsible for epidemics of respiratory illness that occur almost every winter and are often associated with increased rates for hospitalization and death. As it was mentioned in the previous chapter, influenza A virus has also the capability of developing into pandemic virus. Type C infection usually causes either a sporadic mild or asymptomatic respiratory illness or no symptoms at all (Smith, 2003). In comparison to B and C influenza types which are specific to humans, type A viruses can have different hosts, both birds and different mammals (e.g. horses and pigs) including humans (Ã…sjà ¶a and Kruse, 2007). Specifically, influenza B virus strains appear to infect naturally only humans and have caused epidemics every few years (Schmitt and Lamb, 2005). On the other hand, influenza A viruses are significant animal pathogens of poultry, horses and pigs, and multiple antigenically diverse strains exist in a aquatic wild bird reservoir (Garcia-Sastre, 2005). Migrating aquatic birds carry viruses between the continents and thereby play a key role in the continuing process of virus evolution (Murphy et al., 1999). Influenza C virus causes more limited outbreaks in humans and according to Schmitt and Lamb (2005) also infects pigs. Although influenza viruses belong to the best studied viruses, according to Haller et al. (2008), the molecular determinants, which govern the increased virulence of emerging virus strains in humans and which may be associated with their transmission and transmissibility, are presently not well understood. Influenza viruses are negative-strand RNA[1] viruses with a segmented genome (which replicates in the nucleus of the infected cell) belonging to the Orthomyxoviridae family. The morphology of the influenza virion is described in the next chapter. On the basis of antigenic differences influenza viruses are divided into influenza virus types A, B and C. Influenza A viruses are classified on the basis of the antigenic properties of their haemagglutinin (H or HA) and their neuraminidase (N or NA) structural spike-shaped surface glycoproteins (antigens): to date, 16HA (H1-H16) and 9NA (N1-N9) subtypes have been identified (Osterhaus et al., 2008) which gives a theoretical possibility of 144 serological subtypes. Subtypes of influenza A viruses are constantly undergoing small antigenic modifications (antigenic drift) [which is a serotypic change] due to the accumulation of point mutations in their genetic material. In addition, due to the segmented genome, genetic reassortment occurs perio dically when HA and NA genetic material is exchanged between viruses, thereby causing major antigenic changes (antigenic shift) [Yoon and Janke, 2002], the emergence of a new subtype (Smith, 2003) and perhaps the potential for a pandemic outbreak. Both antigenic shift and drift are discussed in  § 1.7. The family Orthomyxoviridae, except the aforementioned influenza viruses A, B and C, also contains the Thogoto viruses. Thogoto viruses are transmitted by ticks and replicate in both ticks and in mammalian species and are not discussed as part of this assignment (Schmitt and Lamb, 2005). 1.4. Influenza Virus Virion This paragraph describes the (belonging to the Orthomyxoviridae family) virus virion[2] morphology. These virions are spherical or pleomorphic, 80-120 nm in diameter (see 1). Some of them have filamentous forms of several micrometers in length. The virion envelope[3] is derived from cell membrane lipids, incorporating variable numbers of virus glycoproteins (1-3) and nonglycosylated proteins (1-2) [Fauquet et al., 2005]. 1. (Left) Diagram of an Influenza A virus (FLUAV) virion in section. The indicated glycoproteins embedded in the lipid membrane are the trimeric hemagglutinin (HA), which predominates, and the tetrameric neuraminidase (NA). The envelope also contains a small number of M2 membrane ion channel proteins. The internal components are the M1 membrane (matrix) protein and the viral ribonucleoprotein (RNP) consisting of RNA segments, associated nucleocapsid protein (NP), and the PA, PB1 and PB2 polymerase proteins. NS2 (NEP), also a virion protein, is not shown (Fauquet et al., 2005). (Right) Negative contrast electron micrograph of particles of FLUAV. The bar represents 100 nm (Fauquet et al., 2005). The lipid envelope is derived from the plasma membrane of the cell in which the virus replicates and is acquired by a budding process (see  § 1.5) from the cell plasma membrane as one of the last steps of virus assembly and growth (Schmitt and Lamb, 2005) which is initiated by an interaction of the viral proteins. Virion surface glycoprotein projections are 10-14 nm in length and 4-6 nm in diameter. The viral nucleocapsid (NP) is segmented, has helical symmetry, and consists of different size classes, 50-150 nm in length (Fauquet et al., 2005). The nucleocapsid segments (the number of which depends on the virus type) surround the virion envelope which has large glycoprotein peplomers (HA, NA, HE). There are two kinds of glycoprotein peplomers[4]: (1) homotrimers of the hemagglutinin protein (NA) and (2) homotetramers of the neuraminidase protein (NA) [see 1 and 2]. Influenza C viruses have only one type of glycoprotein peplomer, consisting of multifunctional hemagglutinin-esterase molecules (HE) [see  § 1.4.1 for further details]. Genomic segments have a loop at one end and consist of a molecule of viral RNA enclosed within a capsid composed of helically arranged nucleoprotein (NP) as it is shown in 2 (Murphy et al., 1999). 2. Schematic representation of an influenza A virion showing the envelope in which three different types of transmembrane proteins are anchored: the hemagglutinin (HA) and the neuraminidase (NA) form the characteristic peplomers and the M2 protein, which is short and not visible by electron microscopy. Inside the envelope there is a layer of M1 protein that surrounds eight ribonucleoprotein (RNP) structures, each of which consists of one RNA segment covered with nucleoprotein (NP) and associated with the three polymerase (P) proteins (Murphy et al., 1999). The aforementioned in the previous paragraph NP protein (arginine-rich protein of approximately 500 amino acids) is the major structural protein of the eight RNPs and it has been found to be associated with the viral RNA segments. Each NP molecule covers approximately 20 nucleotides of the viral RNAs. The NP mediates the transport of the incoming viral RNPs from the cytoplasm into the nucleus by interacting with the cellular karyopherin/importin transport machinery. In addition, the NP plays an important role during viral RNA synthesis, and free NP molecules are required for full-length viral RNA synthesis, but not for viral mRNA transcription (Palese and Garcia-Sastre, 1998). 1.4.1. Influenza Viral Proteins Influenza A and B viruses possess eight single-stranded negative-sense RNA segments (see 2) that encode structural and nonstructural proteins [NS][5]: 1. Hemagglutinin (HA), a structural surface glycoprotein that mediates viral entry (see  § 1.5 for further details) by binding (the HA1 fragment) to sialic acid residues (present on the cell surface) on host fresh target cells, is the main target of the protective humoral immunity responses in the human host (Suguitan and Subbarao, 2007). HA is primarily responsible for the host range of influenza virus and immunity response of hosts to the infection (Consortium for Influenza Study at Shanghai, 2009). After the binding, the virus is taken up into the cell by endocytosis. At this point, the virus is still separated by the endosomal membrane from the replication and translation machinery of the cell cytoplasm (Fass, 2003). HA is initially synthesized and core-glycosylated in the endoplasmic reticulum (ER)[6] as a 75-79 kDa precursor (HA0) which assembles into noncovalently linked homo-trimers. The trimers are rapidly transported to the Golgi complex and reach the plasma membrane, whe re HA insertion initiates the process of assembly and maturation of the newly formed viral particles (33-35). Just prior to or coincident with insertion into the plasma membrane, each trimer subunit is proteolytically and posttranslationally cleaved into two glycoproteins (polypeptides), HA1 and HA2 ( 3), which remain linked by a disulfide bond (Rossignol et al., 2009) and associated with one another to constitute the mature HA spike (a trimer of heterodimers). In that way, the membrane fusion during infection is promoted. Cleavage activates the hemagglutinin (HA), making it ready to attach to receptors on target cells (Murphy et al., 1999). Conclusively and in addition, the HA undergoes various post-translational modifications during its transport to the plasma membrane, including trimerization, glycosylation, disulfide bond formation, palmitoylation, proteolytic cleavage and conformational changes (Palese and Garcia-Sastre, 1998). HA1 is the subunit distal from the virus envelope, whereas HA2 contains a hydrophobic region near the carboxy terminus that anchors the HA1-HA2 complex in the membrane ( 3) [Fass, 2003]. The HA complex is brought to the cell surface via the secretory pathway and incorporated into virions, along with a section of cell membrane, as the virus buds from the cell. HA1 is the subunit distal from the virus envelope, whereas HA2 contains a hydrophobic region near the carboxy terminus that anchors the HA1-HA2 complex in the membrane (see 3) [Fass, 2003]. 3. Primary structure of influenza HA and spatial organization of subunits with respect to the membrane. Cleavage of the influenza HA precursor protein HA0 yields the two subunits HA1 and HA2. HA1 is white, the fusion peptide and transmembrane segments of HA2 are black, and the remainder of HA2 is cross-hatched. For clarity, a monomer of the HA1-HA2 assembly is shown. The amino and carboxy termini of HA2 are labelled ‘‘N and ‘‘C, respectively (Fass, 2003). 2. Neuraminidase (NA) is the other major surface glycoprotein, whose enzymatic function allows the release of newly formed virions, permits the spread of infectious virus from cell to cell, and keeps newly budding virions from aggregating at the host cell surface. This catalytic function of the NA protein is the target of the anti-influenza virus drugs oseltamivir (Tamiflu[7]) and zanamivir (Relenza7). Although these compounds do not directly prevent the infection of healthy cells, they limit the release of infectious progeny viruses thus inhibiting their spread and shortening the duration of the illness. These NA inhibitors are effective against all NA subtypes among the influenza A viruses and may be the primary antiviral drugs in the event of a future pandemic as it proved true in the current â€Å"swine flu† influenza A outbreak. Antibodies to the NA protein do not neutralize infectivity but are protective (Suguitan and Subbarao, 2007). Influenza C viruses lack an NA protein, and all attachment, entry and receptor destroying activities are performed by the aforementioned single spike glycoprotein: hemagglutinin-esterase-fusion (HEF) protein (Garcia-Sastre, 2005). The HEF protein distinguishes the antigenic variants of the genus C of the Orthomyxoviridae family, and the antibody to HEF protein neutralizes infectivity (Schmitt and Lamb, 2005). Of the three virus types, A and B viruses are much more similar to each other in genome organization and protein homology than to C viruses, which suggests that influenza C virus diverged well before the split between A and B viruses (Webster, 1999). Three proteins comprise the viral polymerase of the influenza viruses: two basic proteins (PB1 and PB2) and an acidic protein (PA). They are present at 30 to 60 copies per virion. The RDRP (RNA-dependent RNA polymerase) complex consists of these 3 polymerase proteins (Lamb and Krug, 2001). Together with the aforementioned scaffold protein NP (helically arranged nucleoprotein), these three polymerase proteins associate with the RNA segments to form ribonucleoprotein (RNP) complexes (Murphy et al., 1999). Thus, the RNPs contain four proteins and RNA. Each subunit of NP associates with approximately 20 bases of RNA (Lamb and Krug, 2001). The RNP strands usually exhibit loops at one end and a periodicity of alternating major and minor grooves, suggesting that the structure is formed by a strand that is folded back on itself and then coiled on itself to form a type of twin-stranded helix (Schmitt and Lamb, 2005). RDRP transcribes the genome RNA segments into messenger RNAs (mRNA). The RDR P complex carries out a complex series of reactions including cap binding, endonucleolytic cleavage, RNA synthesis, and polyadenylation[8]. The PA protein may be involved in viral RNA replication and, in addition, the expression of the PA protein in infected cells has been associated with proteolytic activity. The functional significance of the latter activity is not yet understood (Palese and Garcia-Sastre, 1998). Two viral RNA segments (7 and 8) encode at least two proteins each by alternative splicing. Gene segment 7 (see 4) codes for two proteins: matrix protein M1, which is involved in maintaining the structural integrity of the virion, and M2, an integral membrane (surface) protein that acts as an ion channel and facilitates virus uncoating. It is widely believed that the M1 protein interacts with the cytoplasmic tails of the HA, NA, and M2 (or BM2) proteins and also interacts with the ribonucleoprotein (RNP) structures, thereby organizing the process of virus assembly (Schmitt and Lamb, 2005). The drugs amantadine and rimantadine bind to the influenza A M2 protein and interfere with its ability to transport hydrogen ions into the virion, preventing virus uncoating. Amantadine is only effective against influenza A viruses (Suguitsan and Subbarao, 2007). Therefore, for the antiviral therapy, there are two classes of drugs which are currently available for the chemoprophylaxis and the treatment of influenza (Rossignol et al., 2009). These include the aforementioned NA inhibitors oseltamivir and zanamivir, which impair the efficient release of viruses from the infected host cell, and amantadine and rimantadine, which target the viral M2 protein required for virus uncoating. Passively transferred antibodies to M2 can protect animals against influenza viruses, but such M2-specific antibodies are not consistently detected in human convalescent sera (Black et al., 1993), suggesting that this type of immunity may play a minor role in the clearance of influenza virus in humans. Gene segment 8 (see 4) is responsible for the synthesis of the nonstructural protein NS1 and nuclear export protein (NEP, formerly called NS2) [Murphy et al., 1999] which is a minor structural component of the viral core and that mediates nucleo-cytoplasmic trafficking of the viral genome (Garcia-Sastre, 2005). NEP (NS2) plays a role in the export of RNP from the nucleus to the cytoplasm. NS1 protein suppresses the antiviral mechanism in host cells upon viral infection (Chang et al., 2009) and is involved in modulating the hosts interferon response (Garcia-Sastre, 2005). Recently, an unusual 87-amino acid peptide arising from an alternative reading frame of the PB1 RNA segment has been described (Chen et al., 2001). This protein, PB1-F2, is believed to function in the induction of apoptosis[9] as a means of down-regulating the host immune response to influenza infection. Specifically, it appears to kill host immune cells following influenza virus infection. It has been called the influenza death protein (Chen et al., 2001). PB1 segment encodes this second protein from the +1 reading frame. This protein consists of 87-90 amino acids (depending on the virus strain). This protein is absent in some animal, particularly swine, virus isolates. PB1-F2 protein is not present in all human influenza viruses. Human H1N1 viruses encode a truncated version. However, it is consistently present in viruses known to be of increased virulence in humans, including the viruses that caused the 1918, 1957, and 1968 pandemics. PB1-F2 localizes to mitochondria and treatment of cells with a synthetic PB1-F2 peptide induces apoptosis9 (Neumann et al., 2008). 4. Orthomyxovirus genome organization. The genomic organization and ORFs are shown for genes that encode multiple proteins. Segments encoding the polymerase, hemagglutinin, and nucleoprotein genes are not depicted as each encodes a single protein. (A) Influenza A virus segment 8 showing NS1 and NS2 (NEP) mRNAs and their coding regions. NS1 and NS2 (NEP) share 10 amino-terminal residues, including the initiating methionine. The open reading frame (ORF)[10] of NS2 (NEP) mRNA (nt 529-861) differs from that of NS1. (B) Influenza A virus segment 7 showing M1 and M2 mRNAs and their coding regions. M1 and M2 share 9 amino-terminal residues, including the initiating methionine; however, the ORF of M2 mRNA (nt 740-1004) differs from that of M1. A peptide that could be translated from mRNA has not been found in vivo. (C) Influenza A virus PB1 segment ORFs10. Initiation of PB1 translation is thought to be relatively inefficient based on Kozaks rule[11], likely allowing initiation of PB1-F2 translation by ribosomal scanning (Fauquet et al., 2005). In the same way, the M2 protein is anchored in the viral envelope of the influenza A virus, the ion channel proteins BM2 (it is encoded by a second open reading frame10 of RNA segment 7 of influenza B virus, and its function has not been determined) and CM2 are contained in influenza B and C viruses respectively ( 5). The CM2 protein is most likely generated by cleavage of the precursor protein. The influenza B viruses encode one more transmembrane protein, or NB, of unknown function (Garcia-Sastre, 2005). The cellular receptor for the influenza C virus is known to be the 9-0-acetyl-N-acetylneuraminic acid, and its receptor-destroying enzyme is not an NA, as it was already mentioned, but a neuraminate-O-acetylesterase. Like the HA protein of A and B viruses, the HEF of influenza C viruses must be cleaved in order to exhibit membrane fusion activity (Palese and Garcia-Sastre, 1998). 1.5. Viral Entry Influenza virus infection is spread from cell to cell and from host to host in the form of infectious particles that are assembled and released from infected cells. A series of events must occur for the production of an infectious influenza virus particle, including the organization and concentration of viral proteins at selected sites on the cell plasma membrane, recruitment of a full complement of eight RNP segments to the assembly sites, and the budding and release of particles by membrane fission (Schmitt and Lamb, 2005). Viral entry is a multistep process that follows at ­tachment of the virion to the cellular receptor and re ­sults in deposition of the viral genome (nucleocapsid) in the cytosol[12] (receptor-mediated endocytosis). The entry of enveloped viruses is exemplified by the influenza virus ( 6). The sequential steps in entry include (Nathanson, 2002):  § Attachment of the HA spike [the virus attachment protein (VAP)] to sialic acid receptors (bound to glycoproteins or glycolipids) on the cellu ­lar surface (see  § 1.4.1 for further details). This step contributes to pathogenesis, transmission, and host range restriction.  § Internalization of the virion into an endocytic vacuole.  § Fusion of the endocytic vacuole with a lysosome[13], with marked lowering of the pH (see 6). In endosomes, the low pH-dependent fusion occurs between viral and cell membranes. For influenza viruses, fusion (and infectivity) depends on the cleaved virion HA (FLUAV and FLUBV: HA1, HA2; FLUCV: HEF1, HEF2) [Murphy et al, 1999]. The infectivity and fusion activity are acquired by the post-translational cleavage of the HA of the influenza viruses which is accomplished by cellular proteases. Cleavability depends, among other factors, on the number of basic amino acids at the cleavage site. It produces a hydrophobic amino terminal HA2 molecule (Fauquet et al., 2005). 6. Diagram of the stepwise entry of influenza virus at a cellular level. Key events are attachment of the virion; internalization of the virion by endocytosis; lowering the pH of the endocytic vacuole leading to drastic reconfiguration of the viral attachment protein (hemagglutinin, HA1 and HA2); insertion of a hydrophobic domain of HA2 into the vacuolar membrane; fusion of the viral and vacuolar membranes; release of the viral nu ­cleocapsid into the cytosol (Nathanson, 2002).  § A drastic alteration in the structure of the HA1 trimer, with reorientation of the HA2 peptide to insert its proximal hydrophobic domain into the vacuolar membrane (Nathanson, 2002).  § Fusion of viral and vacuolar membranes (Nathanson, 2002).  § Integral membrane proteins migrate through the Golgi apparatus to localized regions of the plasma membrane (Fauquet et al., 2005).  § New virions form by budding, thereby incorporating matrix protein and the viral nucleocapsids which align below regions of the plasma membrane containing viral envelope proteins. Budding is from the apical surface in polarized cells (Fauquet et al., 2005).  § Release of the viral nucleocapsid into the cy ­tosol: After the formation of fusion pores, viral ribonucleoprotein complexes (RNPs) are delivered into the cytosol. RNPs are then transported into the nucleus, where transcription and replication occurs (see 7) [Garten and Klenk, 2008]. How the replication and the transcription of the genome of influenza virus take place in the nuclei of infected cells is summarized in detail by Palese and Garcia-Sastre (1998) [ 7]. (1) Adsorption: the virus interacts with sialic acid-containing cell receptors via its HA protein, and is intenalized by endosomes. (2) Fusion and uncoating: the HA undergoes a conformational change mediated by the acid environment of the endosome, which leads to the fusion of viral and cellular membranes. The inside of the virus also gets acidified due to proton trafficking through the M2 Ion channel. This acidification is responsible for the separation of the M1 protein from the ribonucleoproteins (RNPs), which are then transported into the nucleus of the host cell thanks to a nuclear localization Signal in the NP. (3) Transcription and replication: the viral RNA (vRNA) is transcribed and replicated in the nucleus by the viral polymerase. Two different species of RNA are synthesized from the vRNA template: (a) full-length copies (cRNA), which are used by the polymerase to produce more vRNA molecules; and (b) mRNA. (4) Translation: following export into the cytoplasm the mRNAs are translated to form viral proteins. The membrane proteins (HA, NA and M2) are transported via the rough endoplasmic reticulum (ER) and Golgi apparatus to the plasma membrane. The viral proteins possessing nuclear signals (PB1, PB2, PA, NP, M1, NS1 and NEP) are transported into the nucleus. (5) Packaging and budding: the newly synthesized NEP protein appears to facilitate the transport of the RNPs from the nucleus into the cytoplasm by bridging the RNPs with the nuclear export machinery. M1-RNP complexes are formed which interact with viral proteins in the plasma membrane. Newly made viruses bud from the host cell membrane (Palese and Garcia-Sastre, 1998). 1.5.1. Sialic Acid Receptors of Influenza Viruses Sialic acids (Sias) are a family of negatively charged 9-carbon sugars typically occ Effect of H1N1 Swine Virus on Humans Effect of H1N1 Swine Virus on Humans How does the new H1N1 swine virus infect humans compared to the common influenza virus? SUMMARY Pandemic influenza viruses cause significant mortality in humans. In the 20th century, there are 3 influenza viruses which caused major pandemics: the 1918 H1N1 virus, the 1957 H2N2 virus, and the 1968 H3N2 virus. All three aforementioned pandemics were caused by viruses containing human adapted PB2 genes. In March and early April 2009, a new swine-origin influenza A (H1N1) virus (S-OIV) emerged in Mexico and the United States. During the first few weeks of strain surveillance, the virus spread worldwide to many countries by human-to-human transmission (and perhaps due to the airline travel). In 2 months time, 33 countries had officially reported 5.728 cases resulting in 61 deaths, and by June 2009 WHO reported 30 000 confirmed cases in 74 countries. On June 11 of 2009, this led the World Health Organization (WHO) to raise its pandemic alert to level 5 (Human-to-human spread of the virus into at least 2 countries in 1 WHO region) of 6 (Human-to-human spread of the virus into at least 1 other country in a different WHO region in addition to phase 5 criteria). According to the sayings of Smith et al. (2009), this virus had the potential to develop into the first influenza pandemic of the twenty-first century. In the early summer of 2009, the causes of the human infection and influenza spread among humans had still remained unknown although many publications of that period tried to elucidate this influenza outburst. For example, according to the sayings of Palese, the new H1N1 could also die out entirely. â€Å"Theres a 50-50 chance it will continue to circulate†, he predicts. Conclusively, in that early period, the fuzziness of the data about this new viruss behaviour led scientists only to speculate using past data. Today the 2009 H1N1 virus has ultimately created the first influenza pandemic, has disproportionately affected the younger populations (which perhaps reflects the protection in the elderly due to their exposure to H1N1 strains before 1957), bu t turned out to be not highly pathogenic because the majority of cases of 2009 influenza A H1N1 are mild. Genomic analysis of the 2009 influenza A (H1N1) virus in humans indicates that it is closely related to common reassortant swine influenza A viruses isolated in North America, Europe, and Asia. Therefore, it contains a combination of swine, avian, and human influenza virus genes. More studies need be conducted to identify the unrecognized molecular markers for the ability of S-OIV A (2009 H1N1) to replicate and be transmitted in humans. As a result these additional studies would help us to determine the mechanism by which an animal influenza A virus crossed the species barrier to infect humans. Additionally, these molecular determinants can be used to predict viral virulence and pathogenicity for diagnosis. 1. LITERATURE REVIEW 1.1. Introduction â€Å"Swine flu† †influenza A [Family Orthomyxoviridae (like influenza B and C viruses), Genus Influenzavirus A] is currently the greatest pandemic disease threat to humankind (Salomon and Webster, 2009). The incidence and spread in humans of the â€Å"swine flu† influenza A virus has raised global concerns regarding its virulence and initially regarding its pandemic potential. The main cause of the â€Å"swine flu† has been identified to be the human infection by influenza A viruses of a new H1N1 (hemagglutinin 1, neuraminidase 1) subtype, or â€Å"2009 H1N1 strain† (Soundararajan et al., 2009) that contains genes closely related to swine influenza (SI) [also called swine flu, hog flu and pig flu]. Thus, the strains of virus that cause the annual seasonal flu are different than the new swine flu viruses that emerged in the spring of 2009. Consequently, as it will be analyzed in the subsequent chapters, the new swine flu virus has a unique combinatio n of gene segments from many different sources (a combination that has not been previously reported among swine or human influenza viruses) and specifically is thought to be a mutation of four known strains of the influenza A virus, subtype H1N1: 1. one endemic in (normally infecting) humans, 2. one endemic in birds, 3. and two endemic in pigs (swine). According to Yoon and Janke (2002), the constant evolution of influenza A viruses through mutation and reassortment present a complex and dynamic picture which is to be unfolded in the remaining Literature Review section more specifically for the H1N1 2009 virus. 1.2. Influenza Influenza is historically an ancient disease of global dimension that causes annual epidemics and, at irregular intervals, pandemics. Influenza is an infection of the respiratory tract caused by the influenza virus (see  § 1.3). When compared with the majority of other viral respiratory infections (such as the common cold), the infection by influenza often causes a more severe illness (Smith, 2003). Influenza-like illness (ILI) is defined by the CDC (Centers for Disease Control and Prevention) as fever (with temperature above 37,8 °C) and either cough or some throat in the absence of any other known cause. According to Webster (1999), influenza is the paradigm of a viral disease in which the continued evolution of the virus is of paramount importance for annual epidemics and occasional pandemics of disease in humans which is attributed to the fact that the H1N1 virus does not fit to the strict definition of a new subtype for which most of the population has not any experience of previous infection (Sullivan et al, 2010) as it is justified later in this Literatute Review section ( § 1.8). Influenza is transmitted by inhalation of microdroplets (because the transmission via large-particle droplets requires close contact which is attributed to the fact that these large-particle droplets cannot remain suspended in the air for a long period of time) of respiratory secretions, often expelled by coughing or sneezing, that contain the virus or from other bodily fluids (such as fomites, diarrheal stool etc.). The incubation period is between 1 to 5 days. Symptoms typically include fever, headache, malaise, myalgia, cough, nasal discharge, and sore throat. In severe cases of influenza, a secondary bacterial pneumonia can lead to the death of a patient (Suguitan and Subbarao, 2007). Vaccination and antiviral treatment constitute the two major options for controlling influenza and are the most effective means of preventing influenza virus infection and further transmission in humans. 1.2.1. Pandemic Influenza An influenza pandemic is a large-scale global outbreak of the disease, whereas an epidemic is considered more sporadic and localized. The aforementioned (in the Summary section) situation of pandemic influenza occurs when a previously circulated human influenza A virus [although all the three types (A, B, and C) of influenza viruses can infect humans)] acquires novel antigenic determinants from an animal-origin influenza virus and now can infect and propagate in humans in the absence of any pre-existing immunity (see  § 1.7 for details). Several influenza subtypes have infected humans. Historical accounts led us to consider that an average of three influenza pandemics have occurred each century, at intervals ranging from 10 to 50 years (Garcia-Sastre, 2005). The three influenza pandemics which occurred in the previous (20th) century are: 1. The â€Å"Spanish† influenza pandemic of 1918 (H1N1 subtype), 2. The 1957 â€Å"Asian flu† (H2N2), and 3. The 1968 ‘‘Hong Kong flu (H3N2). These pandemics resulted in high morbidity, death, and also considerable social and economic disruption. They provide health authorities information on which to base preparations for a future pandemic.The first influenza pandemic of the 21st century, due to a new strain of A(H1N1) virus, was declared on 11 June 2009 by the Director-General of the World Health Organization (WHO) [Collin et al., 2009] by raising the H1N1 flu virus pandemic alert level to phase 6 as it was mentioned in the Summary section. Although influenza B viruses do not cause pandemics, during some epidemic years they have caused more significant mortality and morbidity than influenza A viruses (FLUAV) [Garcia-Sastre, 2005]. 1.3. Influenza Virus It was already mentioned that influenza viruses are divided into three types designated A, B, and C (according to the antigenic differences of their internal structural components as it is discussed below in the current chapter). Influenza types A and B are responsible for epidemics of respiratory illness that occur almost every winter and are often associated with increased rates for hospitalization and death. As it was mentioned in the previous chapter, influenza A virus has also the capability of developing into pandemic virus. Type C infection usually causes either a sporadic mild or asymptomatic respiratory illness or no symptoms at all (Smith, 2003). In comparison to B and C influenza types which are specific to humans, type A viruses can have different hosts, both birds and different mammals (e.g. horses and pigs) including humans (Ã…sjà ¶a and Kruse, 2007). Specifically, influenza B virus strains appear to infect naturally only humans and have caused epidemics every few years (Schmitt and Lamb, 2005). On the other hand, influenza A viruses are significant animal pathogens of poultry, horses and pigs, and multiple antigenically diverse strains exist in a aquatic wild bird reservoir (Garcia-Sastre, 2005). Migrating aquatic birds carry viruses between the continents and thereby play a key role in the continuing process of virus evolution (Murphy et al., 1999). Influenza C virus causes more limited outbreaks in humans and according to Schmitt and Lamb (2005) also infects pigs. Although influenza viruses belong to the best studied viruses, according to Haller et al. (2008), the molecular determinants, which govern the increased virulence of emerging virus strains in humans and which may be associated with their transmission and transmissibility, are presently not well understood. Influenza viruses are negative-strand RNA[1] viruses with a segmented genome (which replicates in the nucleus of the infected cell) belonging to the Orthomyxoviridae family. The morphology of the influenza virion is described in the next chapter. On the basis of antigenic differences influenza viruses are divided into influenza virus types A, B and C. Influenza A viruses are classified on the basis of the antigenic properties of their haemagglutinin (H or HA) and their neuraminidase (N or NA) structural spike-shaped surface glycoproteins (antigens): to date, 16HA (H1-H16) and 9NA (N1-N9) subtypes have been identified (Osterhaus et al., 2008) which gives a theoretical possibility of 144 serological subtypes. Subtypes of influenza A viruses are constantly undergoing small antigenic modifications (antigenic drift) [which is a serotypic change] due to the accumulation of point mutations in their genetic material. In addition, due to the segmented genome, genetic reassortment occurs perio dically when HA and NA genetic material is exchanged between viruses, thereby causing major antigenic changes (antigenic shift) [Yoon and Janke, 2002], the emergence of a new subtype (Smith, 2003) and perhaps the potential for a pandemic outbreak. Both antigenic shift and drift are discussed in  § 1.7. The family Orthomyxoviridae, except the aforementioned influenza viruses A, B and C, also contains the Thogoto viruses. Thogoto viruses are transmitted by ticks and replicate in both ticks and in mammalian species and are not discussed as part of this assignment (Schmitt and Lamb, 2005). 1.4. Influenza Virus Virion This paragraph describes the (belonging to the Orthomyxoviridae family) virus virion[2] morphology. These virions are spherical or pleomorphic, 80-120 nm in diameter (see 1). Some of them have filamentous forms of several micrometers in length. The virion envelope[3] is derived from cell membrane lipids, incorporating variable numbers of virus glycoproteins (1-3) and nonglycosylated proteins (1-2) [Fauquet et al., 2005]. 1. (Left) Diagram of an Influenza A virus (FLUAV) virion in section. The indicated glycoproteins embedded in the lipid membrane are the trimeric hemagglutinin (HA), which predominates, and the tetrameric neuraminidase (NA). The envelope also contains a small number of M2 membrane ion channel proteins. The internal components are the M1 membrane (matrix) protein and the viral ribonucleoprotein (RNP) consisting of RNA segments, associated nucleocapsid protein (NP), and the PA, PB1 and PB2 polymerase proteins. NS2 (NEP), also a virion protein, is not shown (Fauquet et al., 2005). (Right) Negative contrast electron micrograph of particles of FLUAV. The bar represents 100 nm (Fauquet et al., 2005). The lipid envelope is derived from the plasma membrane of the cell in which the virus replicates and is acquired by a budding process (see  § 1.5) from the cell plasma membrane as one of the last steps of virus assembly and growth (Schmitt and Lamb, 2005) which is initiated by an interaction of the viral proteins. Virion surface glycoprotein projections are 10-14 nm in length and 4-6 nm in diameter. The viral nucleocapsid (NP) is segmented, has helical symmetry, and consists of different size classes, 50-150 nm in length (Fauquet et al., 2005). The nucleocapsid segments (the number of which depends on the virus type) surround the virion envelope which has large glycoprotein peplomers (HA, NA, HE). There are two kinds of glycoprotein peplomers[4]: (1) homotrimers of the hemagglutinin protein (NA) and (2) homotetramers of the neuraminidase protein (NA) [see 1 and 2]. Influenza C viruses have only one type of glycoprotein peplomer, consisting of multifunctional hemagglutinin-esterase molecules (HE) [see  § 1.4.1 for further details]. Genomic segments have a loop at one end and consist of a molecule of viral RNA enclosed within a capsid composed of helically arranged nucleoprotein (NP) as it is shown in 2 (Murphy et al., 1999). 2. Schematic representation of an influenza A virion showing the envelope in which three different types of transmembrane proteins are anchored: the hemagglutinin (HA) and the neuraminidase (NA) form the characteristic peplomers and the M2 protein, which is short and not visible by electron microscopy. Inside the envelope there is a layer of M1 protein that surrounds eight ribonucleoprotein (RNP) structures, each of which consists of one RNA segment covered with nucleoprotein (NP) and associated with the three polymerase (P) proteins (Murphy et al., 1999). The aforementioned in the previous paragraph NP protein (arginine-rich protein of approximately 500 amino acids) is the major structural protein of the eight RNPs and it has been found to be associated with the viral RNA segments. Each NP molecule covers approximately 20 nucleotides of the viral RNAs. The NP mediates the transport of the incoming viral RNPs from the cytoplasm into the nucleus by interacting with the cellular karyopherin/importin transport machinery. In addition, the NP plays an important role during viral RNA synthesis, and free NP molecules are required for full-length viral RNA synthesis, but not for viral mRNA transcription (Palese and Garcia-Sastre, 1998). 1.4.1. Influenza Viral Proteins Influenza A and B viruses possess eight single-stranded negative-sense RNA segments (see 2) that encode structural and nonstructural proteins [NS][5]: 1. Hemagglutinin (HA), a structural surface glycoprotein that mediates viral entry (see  § 1.5 for further details) by binding (the HA1 fragment) to sialic acid residues (present on the cell surface) on host fresh target cells, is the main target of the protective humoral immunity responses in the human host (Suguitan and Subbarao, 2007). HA is primarily responsible for the host range of influenza virus and immunity response of hosts to the infection (Consortium for Influenza Study at Shanghai, 2009). After the binding, the virus is taken up into the cell by endocytosis. At this point, the virus is still separated by the endosomal membrane from the replication and translation machinery of the cell cytoplasm (Fass, 2003). HA is initially synthesized and core-glycosylated in the endoplasmic reticulum (ER)[6] as a 75-79 kDa precursor (HA0) which assembles into noncovalently linked homo-trimers. The trimers are rapidly transported to the Golgi complex and reach the plasma membrane, whe re HA insertion initiates the process of assembly and maturation of the newly formed viral particles (33-35). Just prior to or coincident with insertion into the plasma membrane, each trimer subunit is proteolytically and posttranslationally cleaved into two glycoproteins (polypeptides), HA1 and HA2 ( 3), which remain linked by a disulfide bond (Rossignol et al., 2009) and associated with one another to constitute the mature HA spike (a trimer of heterodimers). In that way, the membrane fusion during infection is promoted. Cleavage activates the hemagglutinin (HA), making it ready to attach to receptors on target cells (Murphy et al., 1999). Conclusively and in addition, the HA undergoes various post-translational modifications during its transport to the plasma membrane, including trimerization, glycosylation, disulfide bond formation, palmitoylation, proteolytic cleavage and conformational changes (Palese and Garcia-Sastre, 1998). HA1 is the subunit distal from the virus envelope, whereas HA2 contains a hydrophobic region near the carboxy terminus that anchors the HA1-HA2 complex in the membrane ( 3) [Fass, 2003]. The HA complex is brought to the cell surface via the secretory pathway and incorporated into virions, along with a section of cell membrane, as the virus buds from the cell. HA1 is the subunit distal from the virus envelope, whereas HA2 contains a hydrophobic region near the carboxy terminus that anchors the HA1-HA2 complex in the membrane (see 3) [Fass, 2003]. 3. Primary structure of influenza HA and spatial organization of subunits with respect to the membrane. Cleavage of the influenza HA precursor protein HA0 yields the two subunits HA1 and HA2. HA1 is white, the fusion peptide and transmembrane segments of HA2 are black, and the remainder of HA2 is cross-hatched. For clarity, a monomer of the HA1-HA2 assembly is shown. The amino and carboxy termini of HA2 are labelled ‘‘N and ‘‘C, respectively (Fass, 2003). 2. Neuraminidase (NA) is the other major surface glycoprotein, whose enzymatic function allows the release of newly formed virions, permits the spread of infectious virus from cell to cell, and keeps newly budding virions from aggregating at the host cell surface. This catalytic function of the NA protein is the target of the anti-influenza virus drugs oseltamivir (Tamiflu[7]) and zanamivir (Relenza7). Although these compounds do not directly prevent the infection of healthy cells, they limit the release of infectious progeny viruses thus inhibiting their spread and shortening the duration of the illness. These NA inhibitors are effective against all NA subtypes among the influenza A viruses and may be the primary antiviral drugs in the event of a future pandemic as it proved true in the current â€Å"swine flu† influenza A outbreak. Antibodies to the NA protein do not neutralize infectivity but are protective (Suguitan and Subbarao, 2007). Influenza C viruses lack an NA protein, and all attachment, entry and receptor destroying activities are performed by the aforementioned single spike glycoprotein: hemagglutinin-esterase-fusion (HEF) protein (Garcia-Sastre, 2005). The HEF protein distinguishes the antigenic variants of the genus C of the Orthomyxoviridae family, and the antibody to HEF protein neutralizes infectivity (Schmitt and Lamb, 2005). Of the three virus types, A and B viruses are much more similar to each other in genome organization and protein homology than to C viruses, which suggests that influenza C virus diverged well before the split between A and B viruses (Webster, 1999). Three proteins comprise the viral polymerase of the influenza viruses: two basic proteins (PB1 and PB2) and an acidic protein (PA). They are present at 30 to 60 copies per virion. The RDRP (RNA-dependent RNA polymerase) complex consists of these 3 polymerase proteins (Lamb and Krug, 2001). Together with the aforementioned scaffold protein NP (helically arranged nucleoprotein), these three polymerase proteins associate with the RNA segments to form ribonucleoprotein (RNP) complexes (Murphy et al., 1999). Thus, the RNPs contain four proteins and RNA. Each subunit of NP associates with approximately 20 bases of RNA (Lamb and Krug, 2001). The RNP strands usually exhibit loops at one end and a periodicity of alternating major and minor grooves, suggesting that the structure is formed by a strand that is folded back on itself and then coiled on itself to form a type of twin-stranded helix (Schmitt and Lamb, 2005). RDRP transcribes the genome RNA segments into messenger RNAs (mRNA). The RDR P complex carries out a complex series of reactions including cap binding, endonucleolytic cleavage, RNA synthesis, and polyadenylation[8]. The PA protein may be involved in viral RNA replication and, in addition, the expression of the PA protein in infected cells has been associated with proteolytic activity. The functional significance of the latter activity is not yet understood (Palese and Garcia-Sastre, 1998). Two viral RNA segments (7 and 8) encode at least two proteins each by alternative splicing. Gene segment 7 (see 4) codes for two proteins: matrix protein M1, which is involved in maintaining the structural integrity of the virion, and M2, an integral membrane (surface) protein that acts as an ion channel and facilitates virus uncoating. It is widely believed that the M1 protein interacts with the cytoplasmic tails of the HA, NA, and M2 (or BM2) proteins and also interacts with the ribonucleoprotein (RNP) structures, thereby organizing the process of virus assembly (Schmitt and Lamb, 2005). The drugs amantadine and rimantadine bind to the influenza A M2 protein and interfere with its ability to transport hydrogen ions into the virion, preventing virus uncoating. Amantadine is only effective against influenza A viruses (Suguitsan and Subbarao, 2007). Therefore, for the antiviral therapy, there are two classes of drugs which are currently available for the chemoprophylaxis and the treatment of influenza (Rossignol et al., 2009). These include the aforementioned NA inhibitors oseltamivir and zanamivir, which impair the efficient release of viruses from the infected host cell, and amantadine and rimantadine, which target the viral M2 protein required for virus uncoating. Passively transferred antibodies to M2 can protect animals against influenza viruses, but such M2-specific antibodies are not consistently detected in human convalescent sera (Black et al., 1993), suggesting that this type of immunity may play a minor role in the clearance of influenza virus in humans. Gene segment 8 (see 4) is responsible for the synthesis of the nonstructural protein NS1 and nuclear export protein (NEP, formerly called NS2) [Murphy et al., 1999] which is a minor structural component of the viral core and that mediates nucleo-cytoplasmic trafficking of the viral genome (Garcia-Sastre, 2005). NEP (NS2) plays a role in the export of RNP from the nucleus to the cytoplasm. NS1 protein suppresses the antiviral mechanism in host cells upon viral infection (Chang et al., 2009) and is involved in modulating the hosts interferon response (Garcia-Sastre, 2005). Recently, an unusual 87-amino acid peptide arising from an alternative reading frame of the PB1 RNA segment has been described (Chen et al., 2001). This protein, PB1-F2, is believed to function in the induction of apoptosis[9] as a means of down-regulating the host immune response to influenza infection. Specifically, it appears to kill host immune cells following influenza virus infection. It has been called the influenza death protein (Chen et al., 2001). PB1 segment encodes this second protein from the +1 reading frame. This protein consists of 87-90 amino acids (depending on the virus strain). This protein is absent in some animal, particularly swine, virus isolates. PB1-F2 protein is not present in all human influenza viruses. Human H1N1 viruses encode a truncated version. However, it is consistently present in viruses known to be of increased virulence in humans, including the viruses that caused the 1918, 1957, and 1968 pandemics. PB1-F2 localizes to mitochondria and treatment of cells with a synthetic PB1-F2 peptide induces apoptosis9 (Neumann et al., 2008). 4. Orthomyxovirus genome organization. The genomic organization and ORFs are shown for genes that encode multiple proteins. Segments encoding the polymerase, hemagglutinin, and nucleoprotein genes are not depicted as each encodes a single protein. (A) Influenza A virus segment 8 showing NS1 and NS2 (NEP) mRNAs and their coding regions. NS1 and NS2 (NEP) share 10 amino-terminal residues, including the initiating methionine. The open reading frame (ORF)[10] of NS2 (NEP) mRNA (nt 529-861) differs from that of NS1. (B) Influenza A virus segment 7 showing M1 and M2 mRNAs and their coding regions. M1 and M2 share 9 amino-terminal residues, including the initiating methionine; however, the ORF of M2 mRNA (nt 740-1004) differs from that of M1. A peptide that could be translated from mRNA has not been found in vivo. (C) Influenza A virus PB1 segment ORFs10. Initiation of PB1 translation is thought to be relatively inefficient based on Kozaks rule[11], likely allowing initiation of PB1-F2 translation by ribosomal scanning (Fauquet et al., 2005). In the same way, the M2 protein is anchored in the viral envelope of the influenza A virus, the ion channel proteins BM2 (it is encoded by a second open reading frame10 of RNA segment 7 of influenza B virus, and its function has not been determined) and CM2 are contained in influenza B and C viruses respectively ( 5). The CM2 protein is most likely generated by cleavage of the precursor protein. The influenza B viruses encode one more transmembrane protein, or NB, of unknown function (Garcia-Sastre, 2005). The cellular receptor for the influenza C virus is known to be the 9-0-acetyl-N-acetylneuraminic acid, and its receptor-destroying enzyme is not an NA, as it was already mentioned, but a neuraminate-O-acetylesterase. Like the HA protein of A and B viruses, the HEF of influenza C viruses must be cleaved in order to exhibit membrane fusion activity (Palese and Garcia-Sastre, 1998). 1.5. Viral Entry Influenza virus infection is spread from cell to cell and from host to host in the form of infectious particles that are assembled and released from infected cells. A series of events must occur for the production of an infectious influenza virus particle, including the organization and concentration of viral proteins at selected sites on the cell plasma membrane, recruitment of a full complement of eight RNP segments to the assembly sites, and the budding and release of particles by membrane fission (Schmitt and Lamb, 2005). Viral entry is a multistep process that follows at ­tachment of the virion to the cellular receptor and re ­sults in deposition of the viral genome (nucleocapsid) in the cytosol[12] (receptor-mediated endocytosis). The entry of enveloped viruses is exemplified by the influenza virus ( 6). The sequential steps in entry include (Nathanson, 2002):  § Attachment of the HA spike [the virus attachment protein (VAP)] to sialic acid receptors (bound to glycoproteins or glycolipids) on the cellu ­lar surface (see  § 1.4.1 for further details). This step contributes to pathogenesis, transmission, and host range restriction.  § Internalization of the virion into an endocytic vacuole.  § Fusion of the endocytic vacuole with a lysosome[13], with marked lowering of the pH (see 6). In endosomes, the low pH-dependent fusion occurs between viral and cell membranes. For influenza viruses, fusion (and infectivity) depends on the cleaved virion HA (FLUAV and FLUBV: HA1, HA2; FLUCV: HEF1, HEF2) [Murphy et al, 1999]. The infectivity and fusion activity are acquired by the post-translational cleavage of the HA of the influenza viruses which is accomplished by cellular proteases. Cleavability depends, among other factors, on the number of basic amino acids at the cleavage site. It produces a hydrophobic amino terminal HA2 molecule (Fauquet et al., 2005). 6. Diagram of the stepwise entry of influenza virus at a cellular level. Key events are attachment of the virion; internalization of the virion by endocytosis; lowering the pH of the endocytic vacuole leading to drastic reconfiguration of the viral attachment protein (hemagglutinin, HA1 and HA2); insertion of a hydrophobic domain of HA2 into the vacuolar membrane; fusion of the viral and vacuolar membranes; release of the viral nu ­cleocapsid into the cytosol (Nathanson, 2002).  § A drastic alteration in the structure of the HA1 trimer, with reorientation of the HA2 peptide to insert its proximal hydrophobic domain into the vacuolar membrane (Nathanson, 2002).  § Fusion of viral and vacuolar membranes (Nathanson, 2002).  § Integral membrane proteins migrate through the Golgi apparatus to localized regions of the plasma membrane (Fauquet et al., 2005).  § New virions form by budding, thereby incorporating matrix protein and the viral nucleocapsids which align below regions of the plasma membrane containing viral envelope proteins. Budding is from the apical surface in polarized cells (Fauquet et al., 2005).  § Release of the viral nucleocapsid into the cy ­tosol: After the formation of fusion pores, viral ribonucleoprotein complexes (RNPs) are delivered into the cytosol. RNPs are then transported into the nucleus, where transcription and replication occurs (see 7) [Garten and Klenk, 2008]. How the replication and the transcription of the genome of influenza virus take place in the nuclei of infected cells is summarized in detail by Palese and Garcia-Sastre (1998) [ 7]. (1) Adsorption: the virus interacts with sialic acid-containing cell receptors via its HA protein, and is intenalized by endosomes. (2) Fusion and uncoating: the HA undergoes a conformational change mediated by the acid environment of the endosome, which leads to the fusion of viral and cellular membranes. The inside of the virus also gets acidified due to proton trafficking through the M2 Ion channel. This acidification is responsible for the separation of the M1 protein from the ribonucleoproteins (RNPs), which are then transported into the nucleus of the host cell thanks to a nuclear localization Signal in the NP. (3) Transcription and replication: the viral RNA (vRNA) is transcribed and replicated in the nucleus by the viral polymerase. Two different species of RNA are synthesized from the vRNA template: (a) full-length copies (cRNA), which are used by the polymerase to produce more vRNA molecules; and (b) mRNA. (4) Translation: following export into the cytoplasm the mRNAs are translated to form viral proteins. The membrane proteins (HA, NA and M2) are transported via the rough endoplasmic reticulum (ER) and Golgi apparatus to the plasma membrane. The viral proteins possessing nuclear signals (PB1, PB2, PA, NP, M1, NS1 and NEP) are transported into the nucleus. (5) Packaging and budding: the newly synthesized NEP protein appears to facilitate the transport of the RNPs from the nucleus into the cytoplasm by bridging the RNPs with the nuclear export machinery. M1-RNP complexes are formed which interact with viral proteins in the plasma membrane. Newly made viruses bud from the host cell membrane (Palese and Garcia-Sastre, 1998). 1.5.1. Sialic Acid Receptors of Influenza Viruses Sialic acids (Sias) are a family of negatively charged 9-carbon sugars typically occ