An Analysis Of Internet Businesses

An Analysis Of Internet Businesses The reason for writing this essay is to discuss The Advantages and Disadvantages of conducting business on the Internet in the Twenty First Century. In the Twenty First century the advantages and the disadvantages of the use of the Internet is tremendous worldwide. There is enormous benefit to achieve when conducting a business on the Internet. You may ask why I should invest on the Internet. It is to your advantage to invest wisely. It allows access 24/7 and 365 days a year, therefore, no need to hire office helpers for shift or normal working hours, people will visitors your website since there are computers with Internet access, which they can use to gain access the website at anytime anywhere. On the other while there are advantages on the Internet for business to do well, there can also be some inauspicious situation or circumstances. No physical contact, such as no eye contact, no face to face communication, products sometime, ordered might be damaged or loss, during delivered, no way of knowing until it is received, as a result loss of time and productivity. Chaotic Most people who organize, operate, and assume a business venture on the Internet know it can be chaotic and disappointing sometime. Nonetheless, with sufficient communication most businesses can gain much benefit from advertising on the Internet and minimize the disadvantage risk that comes along with it. On the other hand, it may prove to have the buying or selling power that produces a relatively constructive position. Services Many services are now provided on the internet such as banking online, I have not gone into the bank for a while, Ive done all my banking online such as paying my college fees. When I am travelling I purchased all my tickets online that usually cost less than if I purchased it off-line. I am using the internet for just about everything it is a great tool. Nevertheless as Buchannan writes one of the advantages it is easy to set up and lead users from one place to the next in a logical manner. The disadvantage is that data is relatively easy to tap into and possible changed.  [1]   Low Cost Internet communication provides the advantage of lower estimate and storing costs, comparing to printing posters, making a radio or television broadcasting or, supporting a media center. It allows good deal consideration for entering new buying or selling. Internet information is ageless the advertisement also make available the advantage of being lasting.  [2]   It allows volunteered playing an important part to examine carefully the goods and the services and leave notes for others to use. It is cost effective; compare the costs of sending out physical mailing to 25,000 addresses, with the costs of an e-mailing to 250.000 e-mail addresses. Reproduction at zero cost Whether 1,000 visitors come to your site or 25,000, the increased cost is marginal.  [3]   Blogging In all likelihood, we have heard about, blogging one might want to know what is it? What helpful or useful benefits will my business derive from it? A blog is an abbreviation for web log and they are web notes containing up-to-date information on hot issues among the Internet community what. It is also an important Search Engine Marketing tool as it is increasingly used to promote online businesses. Having a blog helps your website get better rankings in the search engines.  [4]   When you want to design a blog it is important to set a clear goal with a reasonable purpose in mind. Select a theme that will be beneficial to your website in the long run, and to the people who visit your website. Provide current, relevant and essential topics. Ask for the reason, cause, or purpose? Ask yourself why blogging would be of help to my business on the Internet. Because it offers excellent search engine tools that can make the search engines, perform at a greater speed, and make the website communicate to your all customers and other business. In fact other bloggers will transmit customers to your sit without cost; it gives your site a good chance for success. June 2005, eBay It is known that the Internet attract more shoppers for goods and services, June 2005, eBay, the Worlds online marketplace, occupied the 5th position in the USA top 10 parent companies with a unique audience of 39,468.000 (Nielsen/Net Ratings) The e-learning sector will grow from $10.3 billion in 2002 to $83.1 billion in 2006, and eventually swelling to over $212 billion by 2011 (Consultant Brandon-Hall) E-commerce transactions in 2005 will reach $168 billion and $316 billion in 2010. These estimates include travel, which is typically the biggest e-commerce sales driver. Excluding travel, e-commerce is expected to grow 14 percent in 2005 (Forrester Research) The online travel industry will double its revenues in the next three years, from $38 billion in 2004 to more than $80 billion in 2007 eMarketer.  [5]   The Internet is now known as low cost and most adequate sales tool around, because of link to the Internet, compare to other business. You have a chance to grow your business successful on the Internet with the right type of Internet promoting fundamentals symbol of principles promotion and decent activities According to Real Time Statistics for Measuring Success of Promotion Campaign the most important advantages of Internet advertisement is that its successful and can be seen.  [6]  Buyers, and sellers use program that give immediate results. Some promotion, give visitors the ability to determine the significant of an advertise product. Which allow the customer to evaluate what is good for them and, also allow time for them to make changes of what they buy and how they it. Steve Here is a man by the name of Steve proclaiming in his own words that working from home via the Internet he received unexpected benefit Steve is a 47-year-old father with two boys, Thomas 16 Jack 12. Ive always been the main breadwinner in our household and a little while ago, received notice that the factory for which I managed Health Safety was to close. As our children were both at critical stages of their education we decided to stay in the area and look for work locally. Id always wanted to work for myself and luckily came across the Community Times business. After attending a seminar at their HQ. I quickly realized that the business would not only suit me but would also have benefits to the whole family. I get to work from home, spend more time with my family, watch my boys play football and earn more than ever whilst being in full control of my familys destiny.  [7]   It has being proven there are disadvantages of managing a business on the Internet. Challenge in verifying authenticity records, advertising on the web, challenge for the business and costumers to perform a complete analysis to determine the genuineness of a transactions. As a result most small businesses are open to attack by larceny, with stolen credit cards and stolen information to do online transaction. With Internet credit card and identity fraud on the rise, small businesses are forced to finance costly security measures to reduce their vulnerability to fraudulent transactions.  [8]   Other unfavorable condition isolation no physical contact with buyers therefore more sales opportunity is lost. Enterprise is forced to choose advertising method in order to lure back customers to the website. Nevertheless, the advantages surpass the disadvantages. With sufficient understanding, enterprise can gain to profit from Internet advertisement, particularly those owners small business. Conclusion The Internet is a very effective. It has many advantages; on the other hand, it also has its disadvantages too.

Goodfellas Essay example -- essays research papers

Goodfellas" is a dramatization of life in the New York Mafia. It is based on the accounts of real life ex-gangster turned state evidence. He tells his story from when he was hired by a wiseguy as a teenager in the fifties, to the time he is put in the witness protection program in the seventies.The movie portrays the spirit of the Mafia and demonstrates their distinctive values, customs,gangster like lifestyle. The Mafia is groups of criminals that developed for the purpose of protecting those who can not go to the police for protection. Its roots can be traced back to Sicily, where the Mafia was based on the premise that any member suffering an injustice was to take personal vengeance while avoiding all contact with legal authorities. Even in the modern day American Mafia, each family ruled it's own territory and when others from outside the territory interfered they were dealt with through violent methods.The wiseguys paid for their protection by paying the head of their local family. This payoff was also known as paying tribute to the boss. Many of the Mafia's morals and policies were identified throughout the movie. Some of the informal rules held by the Mafia were the codes of trust and silence. In other words, never rat on a friend and keep your mouth shut. These rules were highlighted when the narrator, Henry Hill, had his first arrest. He was brought to court, defended by a Mafia paid lawyer and after ...

Up The Down Staircase :: essays research papers

Up the Down Staircase   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  By Bel Kaufman The main character of this book is Sylvia Barret she is a recent college graduate, and works as a high school English teacher. Sylvia would like to work in a nice private school, like so many of her friends. Instead Sylvia takes a job with the board of education, in a nieve attempt to reach out to the under privileged inner-city children in public schools. Sylvia battles with so many choices in this book. In the end she makes the right ones. Another character that is important to this book is James J. Mchabe. He signs his name with Adm. Asst. (administrative assistant). Sylvia calls him â€Å"Admiral Ass† because he is always looking over her shoulder. It seems like Mr.Mchabe’s only propose in life is to bother Sylvia and the other teachers. The admiral always seems to find something wrong with the manor the teachers run their classes in.   Ã‚  Ã‚  Ã‚  Ã‚  Bea Schachter is another teacher at Calvin Colidge High School. Bea has been a teacher at Calvin Coolidge for a very long time and she automatically makes Sylvia her friend. Bea shows Sylvia the ropes; what to do, what not to do, where to go, where not to go. That kind of stuff. Bea is a good teacher, and a good friend to Sylvia. One of Sylvia's students is Joe Ferone. Joe is a rebel and a hoodlum. Joe barely ever comes to class. Sylvia really wants to help Joe. Sylvia tries to schedule after school sessions with Joe, but he never shows up. Towards the end of the story I get the feeling Sylvia was starting to fall in love with him. This story takes place in a New York City school in Manhattan, in the nineteen- sixties. The book covers the span of one school semester form September to February. Sylvia Barret, a new teacher is starting her first day in room 304. She finds out that teaching isn’t all that she thought it would be. Her first friend is Bea a veteran teacher who helps Sylvia out by explaining how Calvin Coolidge high works. The writer takes all the craziness of a normal high school and embellishes them; for instance the school guidance counselor is always using big words and thinks all the students need help. And Mr. Mchabe the administrative assistant who is nosy about everything. The Janitor who is never available.

Oedipus’s transition from the beginning to the end Essay

Sophocles’ Greek tragedy, â€Å"Oedipus† displays how fate and destiny, rather than chance, determine the events within human life. It is this fate that turns Oedipus’ seemingly perfect existence full circle, leaving him with less than nothing in the end. During the course of this story, Oedipus undergoes a complete conversion because of his personal quest to find out his true identity. He eventually learns the truth, but at a great cost. He finds that he isn’t who he believed himself to be, and he loses everything in the process. Oedipus therefore undergoes an absolute transition from a kingship to exile, from wisdom to confusedness, from admirability to utter shame. When Oedipus is first seen, he is clearly noted as the ruler of Thebes. The priest in fact regards him as, â€Å"Great King of Thebes and sovereign Oedipus†¦ † (Line 14). At the moment, Thebes is afflicted with a terrible and mysterious plague, which can only be eliminated when the murderer of Laius, the former King of Thebes, is exiled or killed. It is apparent that the people trust and admire their King, and so they look to him for help and guidance. This is why Oedipus acts so swiftly to find Laius’ murderer no matter what the cost may be. Oedipus once again exercises his kingship and power against Creon, upon hearing from Teiresias (a prophet) that he himself killed Laius. He accuses Creon of treason and sentences him to death. Even though the whole chorus and his wife, Iocasta, are against him, his will is still carried out until he himself decides otherwise. Such makes Oedipus the most powerful man at this point. However, as the events progress, Oedipus finds out that he indeed killed Laius. Upon hearing this, Oedipus’ whole world shatters, and he can no longer bear the truth. He blinds and willingly sends himself to exile. Oedipus loses his title and all the power that it stands for. He is left with nothing but his life in the end. Oedipus gained his Kingship by defeating the mythical man eating Sphinx and solving its riddle. The riddle was, â€Å"What has four legs in the morning, two at noon, and three at night? † Oedipus was the only one who answered, â€Å"Man†, causing the Sphinx to finally kill herself. Man crawled as a baby in its youth, walked with both feet during mid life, and walked with a cane when old. Answering this riddle saved the kingdom of Thebes from the feared Sphinx, and so Oedipus was forever recognized for this. Oedipus’ wit, however, was also the cause of his downfall. This is shown during Oedipus’ debate with Teiresias. As Oedipus exclaims, â€Å"†¦ my skill has brought me glory†, Teiresias replies, â€Å"And this success brought you to ruin too† (lines 441-443). In other words, Oedipus fulfilled the dark prophecy placed upon him by defeating the Sphinx and thus, marrying Iocasta. In this tragedy, Oedipus is faced with the riddle of his identity. However, despite his wit, he is never able to solve the riddle on his own. In fact, he is confused practically throughout the course of the story. Iocasta even solves this riddle before he does, explaining her sheer reluctance of him trying to find out. It takes a whole cluster of clues for Oedipus to finally see that he was his father’s murderer, and his mother’s husband. Finally, Oedipus begins the tragedy with all the qualities of an admirable King. Oedipus genuinely loves his subjects, as can be seen in lines 58-60 â€Å"My children, what you long for, that I know indeed, and pity you. † He calls his citizens his children, signifying his seniority, but also his devotion to them. He is proud of his citizens and of himself. He wants to prove that he is a good king to his people, and so he allows Creon to speak his news from Apollo in front of all Thebans. He tells Creon, â€Å"Let them all hear! Their sufferings distress me more than if my own life were at stake† (93-94). Also, he sincerely wants to save his citizens by finding Laius’ murderer as soon as possible. Therefore, he cares about his people even more than he does himself. Towards the end of the story, however, Oedipus becomes the epitome of shame throughout the kingdom of Thebes. In ancient Greece, family and heritage was one of the most important virtues practiced. And thus, killing one’s own father was the most dishonorable action, next to marrying one’s own mother. Oedipus, sadly, performed both of these shameful crimes which were considered worse, even, than mass murder. So Oedipus went from being the pride of Thebes to its worst shame. Oedipus is indeed so ashamed of his actions that he tells his advisor, â€Å"†¦ Quick as you can, I beg, banish me, hide me, slay me! Throw me forth into the sea, where I may sink from view†¦ There is no man alive can bear this load of evil but myself†. Oedipus’ transition is evident in how he is now pleading and begging his own advisor to banish him from Thebes. Thus, Oedipus loses everything, including his own dignity. In conclusion, Oedipus makes a tragic transition from having everything to having nothing. Because of his quest for the truth, he finally found it and suffered the most in the end. However, despite the shame in what Oedipus did, one must still admire his spirit to continue looking for truth. It is admirable how he chose blindness rather than death, and in a way, punished himself for his past sins. Such a trait still makes him a hero, at in that sense. Sources: 1. http://www. users. globalnet. co. uk/~loxias/myth. htm#interpretation 2. http://cgi. sparknotes. com/hlite. rmpl? words=oedipus&pd=0&page=section5. rhtml&guide=%2fdrama%2foedipus.

Multinational Operations in China

Obtaining a big profit is a good sign of success of a company. But before you achieve this kind of accomplishment, one must know the important things that should be considered in doing a business. If a company wants to business in China, one must have a clear understanding of the locale or in particular China where you want to established it. . It is very important to understand and comprehend yourself with the culture of a country before investing capital in your business. China is one of the largest nations in the world and in fact the most populous country in the world; hence there is a wide range of diversity in culture, beliefs and behavior. The company must first understand it before undertaking operations in China. By doing so, one can established a greater possibility of surviving and even succeeding in the venture taken. The company must also know the local business practices before you do business in a particular area in China. China has most diverse cultural differences in the world and understanding its business culture is very vital. Since every country has different culture, what works with one country can not be appropriate for China. Becoming aware of how people think and their business practices can establish better and harmonious relationship with them. Organizational practices, activities and policies must be flexible and adaptable so that it can accustom easily with China’s practices. Having a representative office in union with a strong local private partner and which has access to all important information is very strategic and help to attain success. Setting up a joint venture is a good move for a company but one must ensure that they have selected the correct partner or else both companies will end up in failure. In the management part, Chinese expertise must be integrated or consulted in the decision making process. This will guaranteed that all aspect of China is considered before making a decision. There is a big need of establishing business relationships. Relationship or also known as Guanxi is an essential component in attaining success in China. Top level manager must know the importance of establishing and nurturing close relationship with their customer, supplier and their local counterparts. It is a great help in knowing the domestic market of China and also builds a strong bond that the company can use in need of assistance or in case of trouble. Company must also build a strong relationship with the China’s government officials. Government is the main factor in the economic movements. They play a vital role in ensuring economic stability and administering foreign investments. Approval, application, and authorization of the business can encountered fewer interruptions or delays if one has already established good relations with the regime. Company must know the financial system of China in doing business here. People’s Bank of China is the one responsible for the establishment and implementation of macroeconomic and fiscal policies. PBOC is also responsible for the regulation of currency circulation and domestic financial activities. Seniority is an important in China. Hence, one must be polite in conversing with older people.   Labor relations are also an important factor to secure business stability. The company must established good relations with their employees. They must look for their welfare. The company need human resources, without them company operations may be suspended and may eventually result to the closure of the company if not handled well. It is also important to recognize the preferential policies offered in China so one can be able to take advantage of it. These policies stimulate foreign investments. Industrial policies monitor foreign investment projects. They are classified as encouraged, permitted, restricted and prohibited. China has extremely promoted the subsequent measures to protect intellectual property rights. In fact China has decreed the Patent, Trademark and Copyright law in order to secure such rights. Works must be registered to the related authorities. In line with this, the government of China proclaimed several security measures to monitor the import publication and reproduction of recorded tapes, video tapes and the like. State Press and Publications Administration, must first grant an approval on the import goods and necessary permit papers must ne obtained. It is subjected to further examination of products. Violation of these security measures may result to subtraction of illegal income and closure of business and payment of fines. China has also required all enterprises to maintain books or accounts for all their business related activities. At the end of the year, they are required to pass an annual financial report. Thus, a company that wants a business in China should know this financial reporting and accounting policy. Tax is the main source of fiscal income of China. It plays an important role in strengthening the macro-economic regulation which is responsible for economic and social development. On the other hand, taxation policies are relatively important in every company. Tax contribute to the input cost of the company, thus it is needed to know the tax policy before doing production and market operations. Also, one can know which kind of business has lower or reduced tax and even exempted to pay such kind of charge. Given those kinds of considerations, tips and reminders on doing business in China, the company would surely make profit on it.   Based on the research employee welfare, labor relations are indeed important factors in establishing a business in China. Although the CEO does not believe on this and my only task as a researcher is to gather strategic information, I will still include those findings.   As a prudent researcher, it is important to include such information because it may affect the company; operations, activities and profit.   My task is to gather strategic information on business in China and these findings I assume is still part of my job. If I do not include such information on the research, this may create trouble for the company. My point is, it is safe to include it on the research since I just give it as an extra detail. The task is now on my CEO; whether he still wants to adopt his beliefs or these new finding. References Coble International. (1988-2008). Doing Business in China. Retrieved April 17, 2008 from http://www.importexporthelp.com/doing-business-in-china.htm. Lee, Joseph. Analysis of the Failure and Success of Doing Business in China. Retrieved April 17, 2008 from http://www.china-window.com/china_business/doing_ PKF: Accountants and Business Advisers. Doing Business in China. Retrieved April 17, 2008 from http://www.pkf.com/jahia/webdav/site/pkf/users/emma Williams, De'Edra. (1998-2008). China. Retrieved April 17, 2008 from http://www.cyborlink.com/besite/china.htm.

Bordetella pertussis (bacterium)

Bordetella pertussis (bacterium) Bordetella pertussis is the bacterium that causes pertussis, otherwise known asor whooping cough . Despite vaccination, incidence of pertussis cases have been growing over the last two decades. Current vaccines lack the ability to give long-lasting immunity and must be improved. Complement evasion molecules would make good candidates for vaccine components, because the complement system is essential in the killing of B. pertussis. The complement system is a first line of defense against colonization of bacteria in host tissue. Many bacteria employ complement inhibitors or attract human complement inhibitors to their surface. B. pertussis is no exception on this, however not much is known about the way B. pertussis evades the complement system . Prior to this study a few potential complement inhibitors of B. pertussis were identified. In this study we seek to characterize these proteins in a series of functional immune assays. Under these experimental conditions, we were not able to determine the function of the potential complement evasion molecules. BACKGROUND Bordetella pertussis is a Gram-negative bacterium and the causative agent of pertussis, also called whooping cough. Pertussis is a human-restricted disease of the respiratory tract and highly contagious ( en is dit zo? REF). Regular bouts of coughing produce airborne droplets through which B. pertussis can be transmitted (Jongerius et al. 2014). The disease was on the verge of eradication due to worldwide vaccination, but has been re-emerging in the last two decades. In 2008 there were 16 million cases of pertussis globally as estimated by the World Health Organisation. Possible explanations for the re-emergence are waning of immunity – since in the 1990s a different vaccine was introduced giving less enduring protection – or bacterial strain adaption (Mooi et al. 2014). Like many pathogens B. pertussis developed strategies to evade or repress the host response for successful colonization (REF). Little is known about the mechanisms by which B. pertussis escapes clearanc e by the complement system, a first line of defense in the immune response. Identification and characterization of these immune evasion molecules may lead to the discovery of new targets for anti-inflammatory drugs or new components for vaccines. Here, we try to characterize several potential complement inhibitors of B. pertussis, identified by phage display and genome analysis. Bordetella pertussis virulence factors B. pertussis expresses a variety of virulence factors that enable the bacteria to colonize the upper respiratory tract. The transcription of the majority of these virulence factors are regulated by the activity of the proteins BvgA and BvgS. BvgAS is a two-component system that controls gene expression in response to changing environmental conditions, such as temperature (Fedele et al. 2014). After inhalation the bacteria adhere to the ciliated epithelial cells of the larynx, trachea and bronchi, where they produce secreted toxins and membrane-bound molecules that contribute to the adherence (REF). The toxins damage the mucous layer of the respiratory tract, contributing to the pathogenesis of pertussis. For example tracheal cytotoxin (TCT) is proposed to cause ciliostasis, impairment of ciliary movement, which may explain the intense coughing that characterizes pertussis, as a way to clear excessive mucus (Jongerius et al. 2014). Other secreted toxins include pertussis toxin (PT) an d adenylate cyclase toxin (ACT), which are toxic to host cells including neutrophils, monocytes and lymphocytes (Jongerius et al. 2014 ). Successful colonization is both dependent on the capacity to adhere to cells in the respiratory tract and the ability to ward off the immune response. PT and ACT both repress the immune response by targeting airway resident macrophages and neutrophil recruitment to the airways (Carbonetti et al. 2010). The membrane-bound adhesins include fimbriae (Fim), filamentous hemagglutinin (FHA) and pertactin (PRN), which in addition to facilitating the first step of infection are also suggested to suppress the initial inflammatory response to the infection (Melvin et al. 2014). For example, FHA-deficient Bordetella strains were shown to induce an increased production of pro-inflammatory cytokines, such as IL-17, and increased recruitment of neutrophils to the site of infection when compared to wild-type bacteria (Henderson et al. 2012). In addition to the i mmunomodulating properties of B. pertussis virulence factors, direct binding to components of the immune system, such as the complement system, is accomplished in order to reduce or inhibit the host immune response. This essential step in bacterial pathogenesis is called immune evasion (Rooijakkers et al. 2005). B. pertussis is known to express a small variety of proteins that affect complement-mediated killing: tracheal colonization factor (Tcf), Bordetella resistance to killing A (BrkA) and the autotransporter Vag8 (Jongerius et al. 2014). The complement system The complement system is part of innate immunity and an important host defense mechanism against invading pathogens. The complement system consists of approximately 40 proteins and is present in blood and mucosal tissue, such as the lining of the lungs where they interfere with colonization of bacteria. The system can be initiated through three different pathways: the classical (CP), the lectin (LP) and the alternative pathway (AP). All pathways lead to a cascade of several protein-protein interactions and proteolytic steps leading to cleavage of C3 and C5 in biologically active components. C3a and C5a are able to attract inflammatory cells to the site of infection and activate them. C3b is another cleavage product of C3 and when deposited on the microbial surface stimulates bacterial uptake by phagocytes in a mechanism called opsonization. Besides opsonization and recruitment of phagocytes the complement system can also directly kill bacteria by forming pores into the microbial memb rane and inducing lysis. The pore-forming heteromer is called the membrane attack complex (MAC) and is composed of C5b, C6, C7, C8 and C9. The classical pathway gets activated with binding of antibodies to the microbial surface. IgM or IgG bind to the first complement component C1q, which results in activation of serine proteases that cleave C2 and C4 which in turn form C4b2a, a C3 convertase. The same C3 convertase is formed upon activation through the lectin pathway, in which mannose-binding lectin-associated serine proteases cleave C4 and C2 upon binding of lectin to mannose on the bacterial surface. No specific signal is needed for the alternative pathway to form another C3 convertase: C3bBb, comprising of spontaneously hydrolyzed C3, or C3b generated by the CP/LP, and factor B that is activated by factor D. The C3 convertases (C4b2a and C3bBb) switch to C5 convertases in response to high levels of C3b deposition on the bacterial surface (Jongerius et al. 2007). The complement s ystem does not only directly or indirectly kill bacteria but also has a role in regulating adaptive immunity. Besides regulating B-cell immunity, complement-mediated signaling directly stimulates and modulates T-cell responses (Jongerius et al. 2014) and promotes antigen processing by antigen-presenting cells (Serruto et al. 2010), indirectly influences T-cell activation. On the downside, over-activation or lack of down-regulation of the complement system can result in systemic inflammation during sepsis (Jongerius et al. 2007) and autoimmune diseases when host cells are recognized as non-self and damaged by complement activation (Meri et al. 2013). Complement evasion by Bordetella pertussis In order to survive and successfully colonize the host the bacteria must have strategies to evade the early immune response. It seems especially necessary for B. pertussis to prevent complement activation because it does not express antigen O (Marr et al. 2011). Antigen O is the chain of repetitive oligosaccharides of the lipopolysaccharides in the membrane of most Gram-negative bacteria and works as a protective shield. The Bordetella strains B. parapertussis and B. bronchoseptica express liposaccharide containing this O-antigen, but despite being more virulent B. pertussis lacks O-antigen in its cell wall. B. pertussis expresses a different kind of surface polysaccharide called Bps (Bordetella pertussis polysaccharide) which seems to provide serum resistance, since Bps mutant strains were more sensitive to complement-mediated killing then wild type bacteria (Ganguly et al. 2014). In addition to polysaccharides B. pertussis is known to express several other complement evasion molecu les. Mutants lacking Bordetella autotransporter protein-C (BapC) were less resistant to serum killing, although the mechanism of resistance is yet to be identified (Noofeli et al. 2011). Another autotransporter of B. pertussis, Bordetella resistance to killing A (BrkA) that promotes attachment of the bacteria to human cells, is involved in complement evasion as well (Jongerius et al. 2014). Studies have shown that BrkA reduces C3 and C4 deposition and inhibits formation of MAC (Barnes et al. 2001). BrkA did not affect C1 deposition levels, suggesting BrkA only inhibits the classical pathway however the precise mechanism remains unknown (Barnes et al. 2001). Besides binding to complement components and thereby inhibiting their action by proteolysis or inducing conformational changes, bacteria can also employ a different strategy: to recruit and activate human complement inhibitors. The main regulators of the classical pathway are C4b-binding protein (C4BP) that B. pertussis binds to its surface with filamentous hemagglutinin (FHA) (Berggard et al. 2001), and C1 esterase inhibitor (C1-inh) recruited by B. pertussis autotransporter Vag8 (Marr et al. 2011). Factor H (fH) regulates the activity of the alternative pathway. The AP does not need a specific signal, making every unprotected surface vulnerable; therefore bacteria need to evade this pathway. Many bacteria do so by binding fH via a common binding site, forming a tripartite complex consisting of the microbial receptor, C3b and fH (Meri et al. 2013). This complex inhibits the opsonizing actions of C3b (Meri et al. 2013) and thereby protects the bacteria against phagocytosis. Recent studies show that B. pertussis binds fH at domain 20 (the common binding site) while fH remains its inhibiting properties (Amdahl et al. 2010), but a particular B. pertussis protein that binds fH has not been identified yet. Pertussis vaccines The whole cell pertussis (wP) vaccine was introduced in the 1950, efficiently lowering the cases of pertussis, which was the leading cause of child death before introduction of the vaccine. Unfortunately the vaccine was causing a lot of unwanted side effects in children. This had lead to introduction of an acellular pertussis (aP) vaccine, comprising of just several antigens. Although this vaccine provides a sufficient level of protection for infants to severe pertussis, the incidence of pertussis in adults has been increasing since the introduction of the aP vaccine in the 1990s (Mooi et al. 2013). More awareness and better diagnostics contribute to this increase in pertussis cases, but moreover the protection given by the aP is short-lived. Immunity generated by the wP vaccine is mediated largely by T-helper 1 cells (Th1), whereas aP vaccination results in antibodies that induce Th2 and Th17 responses. Natural immunity is associated with Th1 cells, and hence IFN- production, as is seen in children recovering from whooping cough (Higgs et al. 2012). The adaptive immunity provided by aP vaccination is mainly humoral, promoted by Th2 cells that seem to be less efficient than Th1 cells in clearing B. pertussis infections (Higgs et al. 2012). In addition the provided immunity by aP vaccination is not lasting as long as the wP (Mooi et al. 2014). This occurrence of waning immunity is proposed to be the main cause of re-emergence of infections with B. pertussis. In addition, there is evidence the bacteria have been genetically adapting to the aP vaccines, caused by antigenic variation and selection pressure. In The Netherlands, France, Finland and Japan there are strains circulating that do not express FHA, PT and PRN, components of the aP vaccine used in these countries (Mooi et al. 2014). Future vaccines should be improved by, for example, adding other antigen preparations to provide long-lasting immunity, and additionally to strengthen the immune response. By st rengthening innate immunity, the immune system will be able to directly eliminate the bacteria, preventing transmission and therefore also strain adaptation. The use of complement evasion molecules as vaccine targets would allow faster complement activation upon infection with B. pertussis. In this study we look to identify and characterize such attractive vaccine component candidates. Prior studies Prior to this characterization study a secretome phage display was constructed (Fevre et al. 2014). This phage display was used to identify potential immune evasion molecules. Phage display is the technique of expressing proteins on the surface of a bacteriophage. A phage library comprises of several phage clones that express different proteins, which retain their original shape and behavior. This allows selection of the displayed proteins based on affinity, with successive rounds of selection to identify proteins with high affinity for the selected targets. Secretome phage display, based on whole-genome phage display, is tailored for identification of immune evasion molecules with only secretome proteins being displayed. The bacterial secretome is the collection of all secreted and surface-bound proteins (Fevre et al. 2014). Phage display was performed for the secretome of Bordetella pertussis, with 3 rounds of selection and 7Ãâ€"107 phage clones. The phages were targeted on six co mponents of the complement system: alternative pathway regulating factor H (fH), the opsonin C3b and C3 together with C5 (the two mixed) and C8 together with C9. After the third round there were five hits: BP0069, BP3355, BP0173, BP1251 and fhaC. Supposedly BP1251 and fhaC seem to bind C8 and/or C9, BP0069 binds factor H and BP0173 and BP3355 are suggested to bind a mix of complement components. Analyzing information on chemical parameters (see table 1), gene alignment and genomic context (provided by NCBI Gene, NCBI Protein, BLAST and ExPASy ProtParam) might provide some clues of the functional properties of the proteins, but their complete function is yet unknown. BP0069 is a 43 kD protein which is 97% identical to ABC transporters from B. bronchispetica and around 30% identical to TRAP transporters from several bacteria species, both are transmembrane transporters for nutrients intake. BP3355 is a 18 kDa hypothetical protein, that has no evident homologues. BP0173 is a 24 kD hypothetical protein and BP1251 is a 26 kD putative toxin.

Sustainable Development with Specialisation on Environment and Research Proposal

Sustainable Development with Specialisation on Environment and Agricultural Development - Research Proposal Example ?†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦.4 4.2 specific aims and objectives†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦..5 5.0 background and significance†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦.5 6.0 methodology†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦....6 6.1 Population and study sample†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦.†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦.6 6.2 Data collection†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢ € ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦..6 6.3 Data analysis†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦.†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦7 Name: Instructor: Task: Date: Sustainable Development with Specialization on Environment and Agriculture 1.0 Introduction Sustainable development involves meeting today’s obligation without diminishing the chances of future generations being in a position of meeting their own. Additionally, sustainable development is a path on which we follow to meet our obligations. Agriculture, for instance, when practicing it, one needs to consider the impact it has on the environment. Moreover, agriculture has to be practiced without compromising the chances of future generations practicing it on the same environment (Brandt and Uwe 190). Several factors contribute to the sustai nability of the environment with regards to agriculture. These factors include the ecological impact, economic viability, social justice and cultural appropriateness. Agriculture has a unswerving link with the environment. For this reason, one can only talk of sustainable development when the issue of environmental conservation has been addressed. In order to achieve sustainable development with regards to the environment and agriculture, externalities that have a negative impact on the environment and agriculture have to be eliminated (Alam 84). 2.0 Sustainable Development Overview Sustainable progress requires a functioning ecosystem, a society that is cohesive and an environment that is healthy. Similarly, it stresses on the importance of being flexible to future shocks even their magnitude and probability is unknown or uncertain. Sustainable development affects humans in several dimensions, for instance, monetary efficiency, ecological impacts and the social growth (Gechev 2). H owever, in this case, we are examining the environmental influences of sustainable progress in agriculture. Similarly, sustainable development should not undermine the very fabric of the social and economics systems. However, in this case, agriculture relies on ecological system. For this reason, the viability of sustainable growth assessed from the angle of environmental influence. 3.0 Problem Statement 3.1 Overview Many people in the world currently rely on agriculture as a source of their livelihood hence sustainable development in the agricultural sector has to consider the imposed impact and future consequences of these developments. Similarly, efficient methods of food production have to consider the impact on the environment hence they should not destroy it, and they should be socially acceptable in the community. Due to the major global differences in agricultural practices, there cannot be one way or one remedy for sustainability (Lichtfouse 3). It takes different variation s with place and place. Each society has to