Movie review 2 Example | Topics and Well Written Essays - 250 words

2 - Movie Review Example It represents crime scenes. The director presents this perception when Paul’s wife and daughter are killed and raped respectively, his boss sends him specifically to New York to fight crime (Brian and Winner, 2003). The role race plays in the film is evident when Kersey kills more black muggers with the intent of increasing the number of the white muggers. Race is used to indicate that most for the criminals in the setting were of the black origin and this necessitated the discriminative killing (Brian and Winner, 2003). Gender plays a significant role of indicating that the muggers targeted women in their criminal activities. This is evident from the killing of Kersey’s wife, rape of Kersey’s daughter and the killing of a young woman at the parking garage. In essence, gender is used to show that, women fall victims of the muggers’ criminal activities. Gender is represented as an indicator of the safety loophole. This implies that women needed more safety measures than their male counterparts (Brian and Winner, 2003). Class plays a key role of enhancing criminal activities. It is represented by drug barons who engage in a fierce competition in selling hard drugs such as cocaine. They kill each other’s accomplices. For instance, Zacharias gang competes with brothers Jack and Romero’s gang. This is an elite class but grossly involved in criminal activities. This leaves the society a rotten and unsafe place for peaceful dwelling (Brian and Winner, 2003). The film reflects the political situation of the society. There is no political willingness to solve the problems facing the subjects. The coordination between the police and the Kersey indicates a rotten political set up. The film reflects the aspects of racism in fighting crime and this extends to the broader perspective of a racist political milieu existing tin the society (Brian and Winner,

The Sales Promotion Article Example | Topics and Well Written Essays - 250 words

The Sales Promotion - Article Example They include employment agencies, classified advertisements, web search and other employment placement service sites. The selection is based on key attributes like being self- motivated, having a disciplined work style, ability to close the sale and lastly capability to build a solid customer relationship. Next is the training of the sales team which is done through various programs such as seminars and meetings on Products, Company and Service. Thirdly, there is sales force compensation which is achieved through salaries, commissions, vacations, pensions and even repays for well job-related expenses. Fourthly, there is sales force supervision and subsequent evaluation of their performance for further improvements. Selling is a complex process that involves several steps. First, there is prospecting and qualifying which briefly involves identifying potential customers, then a pre-approach stage which involves knowing more about the needs of customers. Thirdly, there is the meeting of customers for the first time. Then a salesperson has to handle various objections to customer buying, asking the customer for order and finally making a follow-up. Relationship marketing, on the other hand, involves campaigns by aimed at customer satisfaction and retention. The sales promotion program is developed through a number of steps. There is the size of incentive determination and subsequent setting of conditions for participants. Then, a decision is made on promotion and distribution to the sales team.

A History of World in Six Glasses Essay Example for Free

A History of World in Six Glasses Essay A History of World in Six Glasses by Tom Standage: An Analysis In his book, Standage presents the readers not just an evolution of time and unraveling of history but also the embodiment of people and their culture in the image portrayed by the six types of drink. In this paper, we shall deal with the ramification a certain drink can contribute to the evolution of society. In particular, we shall discuss the role played by these drinks in the economic, political and social aspects of human life. Tom Standage reveals how the six drinks have played certain roles in history. First, he mentions beer as the drink that symbolizes the dawn of civilization. According to him, the farmers in the ancient times planted barley and made beer out of it. Also, â€Å"the guys who built the pyramids were paid in beer and bread. It was the defining drink of Egypt and Mesopotamia. Everybody drank it. Today its the drink of the working man, and it was then as well. This denotes that from the beginning, beer had been part of history and commerce as people used it everyday in their meals, and to celebrate occasions. From this, we can also infer that people used the drink to establish connections or build good relationships. The concept of beer being used as a medium for celebration is similar to the way other prodigious drinks are being served today including the wine. â€Å"Wines may be as old as beer or even older† (Standage 2003). Unlike beer, though, wines are more difficult to produce and preserve. The earlier people used it on special occasions such as weddings and other religious rites. In the Bible, we see different kinds of wine befitting occasions or the people who drank them . Wines also served seemingly as the demarcation line between the rich and the poor, with the first able to afford the more precious and older wines. The history of wine suggests its value in commerce as it was used to trade with other countries for metals, leather and even slaves. Today, wine still marks its place in the important events in society from the simplest family gatherings to grand celebrations of the most important people in the society. Spirits such as brandy and rum were mentioned as drinks associated mostly with sailors and pirates. Although they were consumed limitedly due to their effect, these drinks have also evolved with time as they marked history during the 17th Century in the Caribbean islands with sailors tasked to protect planters from pirates and European enemies. Rum was given as a reward to sailors for the sacrifice they endured aboard, but essentially these drinks helped the crew shake off their hardships and nostalgia, and continue with days ahead. To this day, spirits are still very popular among younger generations as they are mixed with juice and other flavors. Another famous drink that originated centuries ago was coffee. From the Arab Peninsula where it first originated, the aroma and taste of brewed beans have traveled across the world, in every house or establishment that appreciates the warmth coffee can bring. Its popularity can be attributed to the concept of alcohol-free drinks during the Age of Reason in the 18th Century. Today, coffee is loved and enjoyed by billions of people not only for its taste and aroma but also for its anti-oxidant effects. Its caffeine content is said to increase the speed of rapid information processing by ten percent, and a cup of regular (caffeine-containing) coffee after lunch helps to counteract the normal post-lunch dip inability to sustain concentration, aiding alertness. Tea, a drink widely associated with China dates back to as early as the third century A. D. According to Standage, it played a leading role in the expansion of imperial and industrial power of Great Britain for many centuries later. Similar to coffee, it helps workers and those who need to stay alert with its caffeine content, which is why tea or coffee breaks have been part of every business establishment. Remarkable of the 19th Century, the Coca-Cola began was introduced to the market by its inventor, the pharmacist John Stith Pemberton. It has become a symbol of the United States due to its unprecedented sales all over the world among popular drinks today. Notes in history ascertain â€Å"East Germans quickly reaching for Cokes when the Berlin Wall fell, while Thai Muslims poured it out into the streets to show disdain for the U. S. in the days leading up to the 2003 invasion of Iraq† (Standage 2003). The popularity of Coca-Cola also represents the rise of consumer capitalism and instigates the emergence of America as a superpower. Overall, Standage believes that it is globalization in a bottle. Seeing the history of the world in these six types of drink, Standage is able to show us the role that each drink played in economy and society in general. It impresses upon us how each stage in history can be changed or affected by what people drink and how each drink reflects the market it represents. In particular, market technologists and economists can make a good sense out of the pattern rooted out by Standage for every drink. They can take note of the marketability of their product based on the points offered inductively by Standage. As established, these drinks have helped change the economic situations of the countries of their origin. In particular, we see these drinks being used for trade as export products and as factors or images responsible for commercialism and achieving niche in the economic scene. We also see how these drinks have become part of the political systems of the world in the form of symbols of unity or disparity among nations. Furthermore, the six drinks have served as images to represent social status, conventions, and individuality of the people who drink them. While it is commendable of Standage to use these drinks as portals to what developed in history, it may also be wise to look at other drinks that similarly mirror our evolution. In this regard, we may suggest the inclusion of other drinks such as juice, chocolate drinks, and other liquids sold today which are very popular among the youth in the present generation, and which do not necessarily explain political or economic status but simply elucidate on the options people take in response to stimuli in their environment. To give an account of these drinks would complete the details of history of his book, not just centering on the antiquities but also explicating on the modern times. Works Cited Ancient Greece. All About Greek Wine. 2003. 24 November 2007. http://www. allaboutgreekwine. com/history. htm. Coffee and Your Health. Heine Brothers’ Coffee. 24 November 2007. http://www. heinebroscoffee. com/. Handwerk, Brian. â€Å"The World in a Glass: Six Drinks That Changed History†. National Geographic News. 3 October 2003. 24 November 2007. http://news. nationalgeographic. com/news/2005/10/1003_051003_six_drinks. html. Jesus Changes Water to Wine. Biblegateway. com. 1995. 26 November 2007. http://www. biblegateway. com/passage/? book_id=50chapter=2version=31. Standage, Tom. A History of World in Six Glasses. Canada: Doubleday Canada, 2005. The Tradition of Rum and the Sea. The Ministry of Rum. 2003. 25 November 2007. http://www. ministryofrum. com/articles. php.

The Strict Internet Censorship Of China

The Strict Internet Censorship Of China Undoubtedly, the Internet has played an active role in the average Chinese life (Internet Content Control in China, p.3) The Internet is expected to enable Chinese to have more chances to access wide-ranging information sources, which are essential for democracy. As a main way of accessing to information, search engine has played a crucial role in the process of building public sphere in china. According to the survey, in the first half-year of 2010, the utilization rate of search engine among all net citizens has increased by 3%, to 76.3%; the number of users for search engine has reached 320 million and. Since 2009, search engine had entered into a period of rapid development of new cycle. Internet users have applied search engine more frequently and turned to Internet and search engine as to the acquisition of all information in life more (CINIC, 2010). Google is the largest search engine company that supplies global information services in the world. In 2006, Google began to operate google.cn for Chinese public. As a global available search engine, Google can provide more sources outside of china to Chinese. In 2005, 32.9% users would use Google to search information in Beijing of china (CINIC, 2005 , P.11). It is generally agreed that Internet contribute to fostering a virtual space of communication by offering new forms of bonding and solidarity on cyberspace new ways of forging cultural communities in local contexts (Morley, 2000). Specifically, peoples open access to information by using global Internet search engines, such as Google may create a healthier public sphere on cyberspace, which can work as a cultural and social space that should be open, diverse and accessible (Golding Murdock, 1991). To this extent, globally available search engine, such as Google, can contribute to establish public sphere in china. It assumed that Google is playing a positive role to facilitate public sphere in china. However, the situation is contrary. Although Google censored considerably less than the other search engines, it also need to obey the regulation and law of censorship of china. Internet companies all acknowledged filtering out and censoring politically sensitive information due to Chinas restrictive censorship policies. When Google complied with Chinese censorship in order to enter Chinas fast-growing market, it became to the tool of Chinese censorship to control the flow of information. Why google cannot facilitate public sphere in china? In general there are two reasons. First reason is that profit motive makes Google compromise with china. Behind the surface tensions between the Chinese regulatory power and Internet corporations, it can be widely acknowledged that the corporate-Chinese government deal provides considerable financial gains to US technology companies by enabling them to attract Chinese consumers in a lucrative Chinese Internet market with appealing, yet non-controversial material (MDMH, P.411). According to the statistics from survey, china is a considerable large market over world. As a company, Googles main goal is to gain the profit, when face to the economic interest, its responsibility to protect the human rights becomes less important. Googles capability of facilitate public sphere is restricted by the censorship of china. Because of the profit motives, Google have to comply the censorship that is the cost of doing business in china (china dilemma, p.4). For chasing the financial benefit, Googles compromise of Chinese censorship undermine its ability of contribute to form public sphere in china. This new alliance between the two different power groups is based on both state and corporate censorship measures. While the global dissemination of Internet communication operates under fundamental corporate guidelines, such as the free market principle along with the freedom of expression ideology, global Internet information flow is also mediated by local censorship and surveillance policies and political particulars within a social context (MDMH, P.411). Strict censorship of china Once google accepted to censor the information that means googles information are under harsh control. China has a very restrict system of censorship on Internet, which curb google to contribute information to establish the public sphere in china. Chinese government control the flow of information on interentet not only limit network services but also monitor traffic and users (Great leap or long march, p.705). Chine Internet censorship can be divided into two parts, one is regulation and law, and another one is the technologic control. Law and regulation was considered as the internal control of Internet in china. It is impossible to block the use Internet, as a result, Chinese government issued the law and regulation to make the access of information were under the officially control. Chinese communist party (CCP) makes the surveillance on the Internet legal by publishing related regulations and laws. Chinese government published a directive to regulate the use of the Internet in 1996(Great leap or long march, p.705). In 1997, Internet control law was added into Chinese Criminal Law. Since 1995, when commercial Internet accounts were began permitting in china, more and more laws issued to control content of Internet. For instance, Decision of the Standing Committee of the National Peoples Congress on Maintaining Internet Security (2000); Measures for Managing Internet Information Services (2000); Provisional Rules for the Administration of the Operation of News Publication Services by Web Sites (2000); Rules for the Administration of Internet Bulletin Board System Services (2000); Rules for the Administration of Computer Internet Bulletin Board System Services in the Colleges (2001); Interim Provisions on the Administration of Internet Publication (2002)50. Other rules are aimed at Internet cafà ©, state secrecy, network security, and encryption, but they also indirectly have a strong impact on Internet content regulation. Even some rules for infrastructure or connections include provisions on content governance (Internet content control in china, p.18). According to the law and regulation in 2000, the forbidden of sensitive content and the restrictions on the distribution of news aim to control the spread the information that be critical to Chinese government. Moreover, Internet service providers (ISPs) and Internet content providers (ICPs) are required to storage users data to monitor whether user post or access to information that are unapproved by Chinese government (Internet in china). For Internet company, they must get ICP licence that allowed it operate business in china. For example, google has to comply the rules on licences that apply a range of permits. According to that, google are imposed to do self-censorship for filtering keywords that unapproved by CCP. If google do not obey the rules, Chinese government can cancel the licences to prohibit googles right to engage business even accuse google. To put the regulation and law into practice, Chinese government also censor the information by using technical means. Millions of dollars have invested to develop the information technology that distributes the system to limit the accessibility of online resources in china (The china Dilemma, p.3). Chinese government is also implementing its own e-government project which is called Government Online Project(E-government in china, p.3). Internet content filtering in china has been considered as the most complex and sophisticated around the world. Chinese government planed the Golden Shield project in 1998 and started that plan in 2003. It claimed that Golden Shied project employ advanced information technology to safeguard the security of online information and crime combating capacity, which aim to develop efficient police work (Golden shield project). It estimated that Golden Shied project had spent 70 million dollars on research to date, and that the total spending would likely be even more than that. One of the most important parts of this project is the Great firewall of china. The main function of the Great firewall is to block the accessing of forbidden materials on sites outside China. The Great firewall employ newer domain name server IP address filtering, URL keyword filtering, Web Server IP address filtering, HTML Response Keyword filtering, and DNS redirection to achieve the goal of blocking undesirable information. One hand, these technologies including the hardware and software are implemented to prevent police work from attack. On the other hand, the most important role of these technologies is to monitor and filter the flow of information. It is argued that google should reject the self-censorship in china. However, under dual pressure of stringent law and advanced technological control, google faces the dilemma in china. There only two choices for google, one is to do self- censorship, another is to be filtered by Great firewall in china. No matter google chose which side, Chinese government will enforce google to filter the keywords that crucial to public debate and democracy. David Drummond, Googles senior vice president, said that if google do not filter keywords, Chinese government could block even more sites which still disappointed Chinese public. (Google rules, p. 41) This is one of the reasons Google, in 2006, started Google.cn. Among other characteristics, Google.cn was more quickly accessed than Google.com because it filtered out content in- side China, bypassing the Great Firewall. For example, a search for Tiananmen Square on Go- ogle.com results in pictures of the man standing in front of the tank, as well as other websites related to 1989. Google.cn, in contrast, shows tourist sites re- lated to the Square and pleasant looking holiday images. No mention is made of the events of 1989.7 Moreover, if a search for images of the Dalai Lama is made on Google.cn, of the 161 images returned only one is of the Tibetan Buddhist. The same search on Google.com results in 2,030 found images.8 If one lived in China it might be forgiven for thinking many of these historical events and persons never existed (Just doing business or doing just business, p.221). The whole system of censorship on Internet works effectively. Why the Internet can be controlled in china? There are two main reasons behind the phenomena. Political aspect makes the role of Internet in china different from other countries. In general, most of keywords censored are related to politics in china and CCP have opened the diffusion of non-political information. Take the BBC sites as a instance, it can be accessed expect political news. As is know to all, china is not a democratic country that has a unique political environment. CCP has absolute authority to affect the public sphere. Since Republic of China has been established in 1949, CCP have made effort to strength the control of ideology by employing sophisticated censorship. The mainly information from Chinese media are used for propaganda. Internet, especially the searching engine used to be the tool to monitor the public opinion to reinforce CCPs one-party regime. In 1990s, when internet has been introduced in china, it has provided a forum of public debate and democracy for Chinese. Then CCP has relaised the important role of internet and apply law and technology to filter the keyword which risk the authority. As Kellner (1999) argues, Internet can be used as a tool for state power to increase the control or can be used as a tool to establish public sphere. According to that, CCP form authoritarian censorship on interenet to enforce it only to server for Government. In addition, CCP control the flow of information outside china because the fear of against Chinese communist government from west countries. For example, Wei Wu (great leap) claimed that since the end of cold war, Chinese government still worried about those anti-chinese communist government reporters from west might offer information on internet to against CCP. While the internet is global available, Chinese can access some information related to democracy and other west ideology. CCP consider that west ideology can affect the public opinion to endanger one-party regime. To safeguard the surveillance, CCP establish the great firewall to block the sites related to those west ideology about democracy and freedom of speech. Besides the political aspect, china has a lack of fundamental social environment of freedom of speech. Most of Chinese people tend have no sense of freedom of speech. Although scholars like Guobin Yang (the power of the internet in china) argued that more and more online debate and movements about democracy have took place online since 1990, china is lack of the basic to form public sphere on Internet. To begin with, Chinese people educated by Marxist which do not emphasise the importance of freedom of speech. Since 1949, Marxist which is the mainstream ideology in china is deferent from west ideology about democracy. To this extent, Chinese people do not have deep understan of democracy and freedom of speech, which are negative to establish the public sphere. Furthermore, Chinese citizen trend to have more concerns about economy than politicos. Generally speaking, china is a developing country with large population. A number of people in china focus on the developing of economy to improve their level of life condition rather than consider the public sphere. For some Chinese people who are suffering from poverty, the freedom of speech even is a luxury right (Internet content contrl). Future of Google and china Because of hack attack, Google.cn was shut down on 12 January 2010 and visitors are now being redirected to Google.com.hk (google rules). It is believed that Google.com.hk is an appropriate way to solve the problem between china and Google (Google offical blog). Google.com.hk is legal to uncensored and provide more information, yet it would be filtered by Great firewall even it has the risk to be prohibited in mainland of china. As a result, it is difficult to judge that whether google.com.hk can continue to supply information to facilitate public sphere in china. Googles ability to contribute public sphere of china still depends on the censorship of china. David Drummond argued that governments in the West should put pressure on Chinese government to improve the internet enviroment in china(Google rules, p. 35). U.S. government and the European Union have not complained or strongly against Chinas filtering of the Internet. The U.S. Congress has not passed its own laws or resolutions to address the issue of censorship in China. It continues to support business with China (Google china). Nevertheless, Chinese government is under pressure recently and attempting to establish more open and transparent media system. One significant example is the filtering during the 2008 Olympic Games. In 2001, Chinese government promised that there would be no restrictions on journalists in reporting on the Olympic Games (Access controlled, p.468). Although some websites were still blocked, websites containing politically sensitive content were accessible during 2008 Olympic Games. Moreover, most international social media websites were accessible, such as Blogspot, Facebook, and Twitter. Another example is happened in 2010 shanghai expo in china. Computer users can access to most of websites that may blocked before. These two examples indicates that Chinese government has realised that their responsibility to create more open public sphere for Chinese and international public. The open of internet environment just need to be taking gradually in china. Conclusion This emerging public sphere on the Web tends to enable more democratic sharing of information and lead to a new political awareness based on informed civic engagement (Fischer, 2000). However, average citizens are not in a good position relative to both global corporate forces and influential government regulatory regimes in terms of making rules and policies to manage the global flow of cyber- communication. Given that technology brings change, both positive and negative, in relation to social interactions and power dynamics, it should be recognized that technology also involves regulation or restriction by the state or other social forces because the information technology, i.e., the Internet, is not separated from the social and political context in which it is created and operated (Marshall, 2003; Fischer, 2000). The question is no longer how the Internet will affect china; it is how china will affect the Internet (Who controls the internet, p.104).

Uses of Marijuana :: Free Essays Online

Hemp is a very useful plant. The reason why it is illegal today seems an easy question to answer, right? Because of the effects that it causes on the brain and body. Right? Wrong! The reasons why hemp was made illegal were reasons that the public were never exposed to. Before 1883 about seventy-five to ninety percent of the world's paper was manufactured from hemp bast fiber. The United States Department of Agriculture first proposed making paper from hemp pulp in the early 1930's. Although production had to wait until someone invented a machine that would separate the hemp pulp from the fiber cheaply. Meanwhile, Dupont Chemicals, Hearst Paper and Timber, and several other companies had developed a new way to make whiter paper out of trees. Just when they got all their patents and business going in 1936, someone invented the hemp 'decorticating' machine. This threatened to put all the tree companies out of business, because of the fact that hemp paper is cheaper to make. A huge sum o f capital was tied up in making tree pulp paper and shipping it for sale. Most of the tree-paper companies were very powerful and had many connections with the government. So in 1937, they launched a country-wide campaign to put a prohibitive tax on hemp. This was the first 'Reefer Madness Movement' and when we began to call cannabis-"Marijuana". At that time no one knew that marijuana was really cannabis hemp. The only knowledge about hemp that the public knew had been obtained from the many fabricated stories. All the public knew was that it was "the killer weed with roots in hell", because of the supposedly harmful effects that it had on the human body and mind, which by the way have all been reaserched again in depth and the previous conclusions of the effects of marijuana on the human body and mind, have all been disproven. Because of this most American's did not know where their clothes used to come from because synthetic fabrics had just becom popular. The first Levi's blue j eans were made from the hemp plant. I will including the following information in my paper; the many useful uses of hemp as a perspective product for the future, products such as; fiber, rope and twine, canvas, cloth and cotton, how it can replace our dependence on our forests for our paper products, and finally how easily it can be cultivated.

The Fenian Movement :: Essays Papers

The Fenian Movement In 1884 a movement started that changed Ireland forever. The Fenian Movement evolved because of the horrible deeds of King Henry VIII and his durable militia. Britain was trying to govern Ireland, and the people of Ireland fought for the freedom of there country. They didn’t have much money or much military action, on the other hand Britain did. This wasn’t the only reason the Fenian movement occurred though the great potato famine 1845 forced people from there homeland. The Fenian movement was when the people of Ireland were forced from there homeland because of the lack of natural resources and military action by the British. Another aspect to the Fenian movement was that Irish citizens didn’t have much money because they are not industrialized and they have an agricultural economy, which led up to the potato famine. Irish farmers didn’t have enough money to produce potatoes efficiently; this is when the blight occurred. Another branch that led from living in poverty was lack of military supplies. This was a huge problem because they couldn’t protect there country or even there freedom. Due to lack of funds many people migrated over seas to America where they could make money and live a successful life. In Ireland potatoes were the most popular product. â€Å"The potato grew well in Irish soil, producing the high yields that small-pot tenant farmers needed to feed their families and pay their rent†(Michael 1). During the potato famine the farmlands in Ireland were rotting away due to the blight. â€Å"Beginning with 1847, the potato blight left famine and death on every hand; emigration was excessive, and disaffection widespread, yet the British government did little to relieve the deplorable conditions. Goaded by almost unbearable economic distress, the young Irelanders decided to act†(Walker, 2) This led to poverty, migration and even death( how many people). People in Ireland were forced out of there homes to other countries because of the horrible natural resources. Many people starved, and these unfortunate citizens migrated to the United States, Canada, South America, and Australia. Ship-owners packed hundreds of boats to flee from Ireland to English speaki ng countries. Many of the Irish people didn’t even make it to these countries because of the horrible disease typhoid. Another one of the major causes of this horrific problem in Ireland was that British military decided they wanted to take over the Irish government and control the land.

Carbohydrate and Peptide †Based Vaccines: The Way Forward

Abstract Existing treatments and therapies have supported a huge variety of diseases and infections, a significant example being antibiotics. However the increasing presence of multi-resistant bacteria, as well as increased changes observed in the mechanisms responsible for variation in viruses, involving accumulation of mutations within the genes that code for antibody-binding sites (known as antigenic drift), has resulted in these new strains not being inhibited as effectively by those treatments that originally targeted them (Reche, Fernandez-Caldas, Flower, Fridkis-Hareli and Hoshino, 2014). The knock-on effect has been that the bacteria or virus is able to spread more easily, and therapeutic treatments (used after a person contracts a disease), become less effective, unable to work by boosting the host’s own immune system. As a result, it has been recognised that the vaccine offers the advantage of preventing the anticipation of disease occurrence, using advance action to countera ct infection and chronic illness. Prophylactic, and to a lesser extent therapeutic, vaccines are the most cost-effective and efficient alternative to other treatments and prevention of infectious and chronic diseases. They work by causing changes to the T- and B-cells of the adaptive immune system to eliminate or prevent pathogen growth (Plotkin, Orenstein, and Offit, 2013). Going back to the introduction of vaccines more than 200 years ago, these were initially composed of killed pathogens, which although successful, also caused unacceptably high levels of adverse reactions. During the years of research that have since followed, as with the changes observed with antibiotics and other treatments becoming less effective, the need for safer and more effective vaccines has also been acknowledged. In addition, an improved understanding of antigen presentation and subsequent recognition has supported the development of newer vaccine types (Flower, 2013). Equally, whilst many diseases and infections are controlled by vaccines, for some, no vaccines have been developed, including Streptococcus pyogenes, human immunodeficiency virus (HIV) and hepatitis C virus (HCV) (Wang and Walfield, 2005; Barrett and Stanberry, 2009). Efforts to develop new vaccines are discussed in more details, with a focus on peptide-based and carbohydrate-based vaccines. Challenges are also discussed, leading to a summary of the potential direction of vaccination and research, which describes a promising future. Peptide-based vaccines An example of a newer category of vaccine is peptide-based vaccines. Peptides are short sequences of proteins, and diseases/infections use these proteins as part of their attack on the immune system. In many cases, the immune system has the ability to recognise the proteins associated with an attack by disease or infectious causing pathogens and can respond effectively. However as observed with many cancers, HIV, HCV and other conditions, an effective immune response is not triggered, hence the need for newer vaccine developments including those based on peptides, which encompass single proteins or synthetic peptides encompassing many antigenic determinants (B- and T-cell epitopes) (Flower, 2013). Peptide vaccines are a type of subunit vaccine, which presents an antigen to the immune system, using the peptide of the original pathogen, supporting immunity. Such peptide-based vaccines avoid the adverse effects described with traditional whole-organism vaccines (Moisa and Kolesanova, 20 12) with additional benefits also noted (Ben-Yedidia and Arnon, 1997), including: The absence of infectious material An immune response that is specific, focusing only on the targeted epitope, with the induction of site-specific antibodies No risk of an immune attack or cross-reactivity with the host tissues Flexibility, with an ability to modify products accordingly Improved effectiveness in relation to manufacturing on a large scale, and long-term storage where necessary e.g. a pandemic. However, a number of difficulties have been encountered during the development of such vaccines (Simerska, Moyle and Toth, 2011; Dudek, Perlmutter, Aguilar, Croft and Purcell, 2010) including: A short biological activity of peptides due to degradation by enzymes The trigger of a weak immune response when used alone i.e. single peptides Finding optimal delivery systems. As a result, and to overcome the difficulties mentioned above, synthetic peptide vaccines have been developed, on the basis that a greater more accurately targeted immune response will be achieved. Peptide antigens are not immunogenic by themselves, so this has led to investigations into co-administration of subunit peptide antigens with adjuvants (immunostimulants) to increase the peptide-induced responses to corresponding antigens. Appropriate delivery systems and often toxic adjuvants have demonstrated effective immunity, however, although many adjuvants are described in the literature, only a few have been approved for use with vaccines for delivery in humans due to their toxicity and include water/oil emulsions, liposomes, and bacterial lipophilic compounds to offer a few examples (Heegaard et. al., 2010). Incomplete Freund’s adjuvant (IFA) and Montanide ISA (both oil-based) have been used in clinical trials. Focusing on liposomes as another example, researchers have demo nstrated that use of lipid core peptide (LCP) technology (lipidation of peptides) improves the effectiveness of a self-adjuvanting vaccine delivery system, targeting a specific disease and triggering an effective immune response. This system provides a promising platform for human vaccine development (Zhong, Skwarczynski and Toth, 2009; Moyle and Toth, 2008). In animal models, peptide vaccines have been effective in generating the required immune response, and during recent years, peptide-based vaccines have advanced from animal models and pre-clinical studies, to human clinical trials (Yang et al., 2001). Although currently, all known peptide vaccines under development for humans remain at the stage of clinical trials, these trials should build on the promising evidence resulting from research to date of the potential application of vaccine candidates based on a LCP system, as well as other strategies. Prevention of not only many infectious diseases including hepatitis C virus, mal aria, human immunodeficiency virus and group A streptococci), but also for cancer immunotherapy and improved allergen specific tolerance, remains an exciting, and very real possibility. Carbohydrate-based vaccines The development of vaccines based on carbohydrates not only has quite a history, but is also an area that is fast moving in the current research world. The literature provides evidence as far back as the early 1900s where researchers discovered a connection between type-specific polysaccharides and the induction of antibodies being developed against certain types of pneumococci (Francis and Tillett, 1930). This was confirmed by evidence of pneumococcal capsular polysaccharides being used as vaccines, providing effective and long lasting immunity (Heidelberger, Dilapi, Siegel and Walter, 1950). However despite these early findings, the discovery and success of other treatments such as antibiotics and chemotherapeutics led to this area of research being put on hold. As mentioned earlier however, due to increased resistance to existing treatments such as antibiotics, coupled with the recognition for a need of newer treatments including improved vaccines, renewed interest into preventive vaccines has resulted in novel approaches, which include carbohydrate vaccines. Vaccines are commonly made from weakened pathogens, or, as we now know, other approaches also use immunogenic proteins or polysaccharides. Carbohydrates have been the centre of attention in the research field of vaccination because not only do they exhibit more stability than proteins, but they have roles in both physiology and pathophysiology, including cell interaction and signalling, inflammation, pathogen host adhesion/recognition, to name a few examples (Doshi, Shanbhag, Aggarwal, Shahare and Martis, 2011). During the last ten years or so, they have been used as adjuvants, as carriers for protein antigens to aid immunotherapy, and as targets for vaccines against bacteria. Additionally, as observed with DNA and proteins, carbohydrates are now recognised as biopolymers also, playing a role in many molecular and biological activities (Doshi et. al., 2011). These discoveries, partnered by an improved u nderstanding of the immune system and the identification of specific and relevant carbohydrate structures, led to the development of glycoconjugates, which in turn led to carbohydrate vaccine development (Holemann and Seeberger, 2004). Glycoconjugates are present in the surfaces of cells, as well as in the surrounding extracellular matrices and connective tissue. Therefore both the identified structure and presence of glyconjugates, plus the role they play, means they are a suitable basis for the development of new vaccines. Induction of protective antibodies is key to an effective immune response as a result of a vaccine, and as with peptide vaccines, challenges have been evident in the research to develop effective carbohydrate vaccines, including the following: Glycans struggle to effectively induce protective antibodies Carbohydrates have a low immunogenic impact by themselves (as observed with peptides). There are two main carbohydrate vaccine types: 1. Natural carbohydrate vac cines: these include small amounts of impurities 2. Synthetic carbohydrate vaccines: these are produced with no contaminants, and are cost-effective due large-scale production. Synthetic carbohydrate antigens used to develop vaccines have triggered immune responses in clinical studies and are favourable given the risk of adverse effects with natural vaccines. Four crucial aspects need to be considered for the design of carbohydrate-based vaccines (Astronomo and Burton, 2010): The antigen source: glycan antigens are diverse, ranging from large polysaccharide capsules, to small monosaccharides, to oligosaccharides, all of which have been shown to be adequate for preparation of vaccines. The carrier: this is most often proteins, although other materials have been investigated, with the aim of ensuring that the link between the antigen and the carrier is specific. The method of conjugation (or ligation): protein conjugates, lipid conjugates and polyvalent scaffold conjugates have been d eveloped. The success of a conjugate vaccine depends partly on the method of conjugation employed. This should be simple and efficient, as well as causing minimal distortion to the individual components involved, with many differing techniques used (Zou & Jennings, 2009; Ada and Isaacs, 2003). The choice of adjuvant: required to improve immunogenicity of the carbohydrate antigens being targeted, with a limited choice approved for use in humans. Examples of diseases targeted by carbohydrate-based vaccines The discussion will now move on to the use of carbohydrate-based vaccines in three disease areas: Group A Streptococcus (GAS), HIV/AIDS and Haemophilus influenza type b. GAS The need for a safe, effective, affordable and practical vaccine against GAS (also known as Streptococcus pyogenes), has been recognised for many years, as has the research into a vaccine against this disease, given the global burden on health that this disease causes in particular in less developed countries. More than 500,000 deaths result from the GAS each year, with the bacteria causing a range of both less complicated and life-threatening illnesses (Carapetis, Steer, Mulholland and Weber, 2005). The diversity of GAS strains is the major challenge for the development of an anti-GAS vaccine, with more than 100 different strains identified, of which the genetic sequence for several different strains have been determined (Johnson and Pinto, 2002). Rese arch has identified that GAS bacteria contain a surface polysaccharide made up of long, repetitive polysaccharide chains. The conserved and constant arrangement of these chains suggests conjugate vaccines to be an attractive and achievable option, with animal models supporting this theory (Cunningham, 2000). Synthetic carbohydrate vaccines, although only studied in a limited set of GAS infections, have demonstrated a protective immune response (Robbins et al., 2009). In addition, some areas of research have focused on the molecular analysis of a surface protein labelled the M protein, which is encoded by the emm gene. This particular gene has been found to be the major cause of GAS related clinical manifestations (Smeesters, McMillan and Sriprakash, 2010). These findings have allowed a greater understanding of the functioning of specific proteins responsible for the virulence of the disease, which in turn, supports the development of potential GAS vaccines. Vaccine prevention of GAS and the resulting symptoms and complications has been a goal of researchers for many years. A number of vaccines have been in research development to offer protection against GAS, with the research vaccine strategies focusing on either M protein, or non-M protein antigens (Smeesters, 2014). However only those vaccines that use the M protein as the antigen have progressed to clinical trials (McNeil et. al., 2005), and have included conserved antigens coverage across the many strains of GAS, a type-specific vaccine based on the N-terminal portion of the M protein, and a recombinant vaccine that reached phase II clinical trials (Pandey, Wykes, Hartas, Good and Batzloff, 2013; Bauer, 2012). However no vaccine has currently reached licensing and so the diseases caused remain uncontrolled in many areas, with reviews covering the research suggesting that even those vaccines developed with the aim of providing large coverage of GAS strains, these vaccine might achieve acceptable coverage i n developed countries, but in less developed countries where the disease burden is much greater, the positive impact of the vaccines would be much lower due to a greater strain diversity (Smeesters, McMillan, Sriprakash, and Georgousakis, 2009; Steer, Law, Matatolu, Beall and Carapetis, 2009; McMillan and Sanderson, 2013). Equally, antibiotic treatment is either impractical with regards to implementation (specifically in less developed countries) or ineffective. One research group targeted the bacteria by synthesising a new self-adjuvanting vaccine candidate, incorporating a carbohydrate carrier and an amino acid-based adjuvant, resulting in successful synthesis and characterisation of the vaccine candidate. This may contribute to the identification of a safe and effective vaccine against GAS in the future (Simerska et. al., 2008; Simerska, Lu and Toth, 2009). HIV/AIDS One of the main challenges researchers have faced within the field of vaccine development against HIV/AIDS, is that the virus surface is covered with layers of glycans, which conceal underlying viral antigens that are potential good targets in the production of vaccines (Scanlan, Offer, Zitzmann, and Dwek, 2007). They are produced by the host cell, which makes the virus appear as â€Å"self† resulting in no attack being triggered by the host immune system. The layers of carbohydrate also contain mannose residues, making these another potential target for a vaccine aimed at preventing HIV infection, whereby lectins preferentially bind to ? 1-2 linked mannose residues. Such lectins are being investigated as possible therapeutic tools (Tsai et al., 2004) although the fact that lectins are often toxic needs to be researched further to avoid the host immune system damaging host cells. Indeed, other drugs that are known to inhibit synthesis of carbohydrates only have this effect at often toxic concentrations to cause antiviral activity. Another strategy based on the same principle of developing a carbohydrate vaccine, is the identification of antibodies that again recognise and bind to glycans. (Scanlan et al., 2002, Scanlan et al., 2007). The antibody appears to recognize these glycans because although they belong to the host, they are arranged in a â€Å"non-self† manner (Scanlan et al., 2002; Scanlan et al., 2007), making the production of effective ant-HIV vaccines a real possibility, in addition to vaccines for other diseases such as cancer (Galonic and Gin, 2007). Studies have also been described using immune enhancing adjuvants, carrier peptides such as keyhole limpet hemocyanin and altered glycan structure constructs that support immune recognition in the development of vaccines against cancer (Galonic and Gin, 2007). These same strategies are being used in development of possible HIV vaccines, where antibodies target self-carbohydrates arranged slightly differently on cancer cells and HIV-infected cells, in comparison to healthy cells. (Galonic and Gin, 20 07). These approaches have not as yet led to clinically effective vaccines, but it is clear that antibodies that strongly bind to carbohydrate antigens on, for example, prostate cancer cells, have been generated (Slovin et al., 2003) and this appears to be a highly promising approach. Further exploration is required based on the carbohydrate coat of the virus, which may lead to improved prevention treatment of HIV. Haemophilus influenza type b The first synthetic vaccine for human application was developed in 2003 for protection against Haemophilus influenza type b vaccine, not only providing protection against this bacterium, but also against all the associated diseases it causes ranging from meningitis, septicaemia, pneumonia and arthritis (Doshi, Shanbhag, Aggarwal, Shahare and Martis, 2011). Indeed this bacterium is the leading cause of serious illnesses in children under 5 years worldwide. The majority of strains of Haemophilus influenza are non-encapsulated, and are lacking in any carbohydrate polysaccharide protective structure, as opposed to the GAS bacteria and HIV virus described earlier. This structural information armed researchers with the knowledge that carbohydrate polysaccharide conjugate vaccines would be required to ensure the development of an effective vaccine (Verez-Bencomo et. al., 2004). As a result, carbohydrate-based vaccines have been licensed for protection in humans against haemophilus influenza type b, using oligomerization and a carrier protein (Doshi et. al., 2011).Evidence of progressTo end this section of the discussion, several conjugate polysaccharide carbohydrate vaccines are now well into pre-clinical/clinical development, or have been licensed and are now commercially available. Examples of licensed vaccines include the following (Astronomo and Burton, 2010): Haemophilus influenza type b (Hib) – 4 carbohydrate-based vaccines are licensed via 3 different pharmaceutical companies: ActHIB and Hiberix; Pentacel; PedvaxHIB; and Comvax Neisseria meningitides A, C, Y and W-135 – 2 carbohydrate-based vaccines are licensed via the same pharmaceutical company: Menactra; and Menomune-A/C/Y/W-135 Salmonella typhi – 1 carbohydrate- based vaccine is licensed: TYPHIM Vi Streptococcus pneumonia variants – 2 carbohydrate-based vaccines are licensed via 2 different pharmaceutical companies: Prevnar; and Pneumovax 23. Examples of carbohydrate-based vaccines in development include the following, where the disease is described in addition to the phase of development (Astronomo and Burton, 2010): Breast cancer – with 1 vaccine at the preclinical phase and a second at phase I Prostate cancer – 4 vaccines are in development at the preclinical, phase I and phase II stages HIV-1 – 1 vaccine at the preclinical phase Group A streptococcus – 1 vaccine at the preclinical phase Group B streptococcus – 1 vaccine at phase II. Conclusion It is fact that vaccines have had a major role to play in the success of preventing and treating many diseases, however many challenges remain. Diseases exist for which no effective vaccines have yet been discovered, including HIV/AIDs. In addition, diseases that have been controlled by vaccines in some parts of the world continue to affect the lives of people adversely in other areas where infrastructures for vaccination are poor/non-existent. Continued research is necessary to develop vaccines not only for those diseases with no vaccine available, but also to improve the effectiveness of existing vaccines. In addition to research focusing on novel and promising approaches such as carbohydrate and peptide based vaccines, efforts also need to concentrate on areas such as lower cost, more convenient delivery of vaccines, and longer-term protection. The future direction of research in this field has become focused with the help of new evidence-based information and promising data. The advent of synthetic peptide-based and carbohydrate-based vaccines signified a new era for vaccines, over-taking traditional treatments and vaccines which have become either ineffective or only offer short term protection. As the discussion demonstrates, a number of vaccines are already successfully protecting humans against some pathogens and disease, with the potential for further vaccines to follow. 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