Culture Clashes in Daisy Miller Essay Example for Free

Culture Clashes in Daisy Miller Essay Throughout the world people have differing ideas on what is good and bad based on whatever culture one visits one is sure to find major differences. In the period that this story takes place the US is trying to find its own identity and establish their own traditions. In the Europeans perspectives the Americans were deviant people because their culture was out of the norm. Winterbourne is stunned and intrigued immediately once he meets Daisy. He growing up with a more European lifestyle finds Daisy’s flirtatious and outgoing attitude very abnormal yet refreshing. Many of the older women in society, especially his mother, find her to be cheap and very unlady like due to her lack of classy behavior compared their idea of a proper high society woman should behave like. The book Daisy Miller, illustrates the American lifestyle, compared to the proper etiquette of European social standards. The novel Daisy Miller is the story of a girl who is on vacation with her mother and little brother. Along the way she meets Winterbourne and whom he immediately notices that she is different than other girls he has met in the past. She gives off an aura of wanting to become independent and a free spirit. Which all of the other women look down upon because they find it very trashy and very improper, especially for someone of such a high status also. Daisy’s family is of high society and normally girls like Daisy are quiet and respectful, never is it heard of to approach a man to which she is not acquainted with. Therefore, the idea that Daisy is flirtatious and so headstrong and direct with Winterbourne is just shocking to everyone who hears of her. She makes a great impact on those around her and unfortunately most do not like her because she is different and American. Henry James was born in New York on April 15, 1843 and died February 28, 1916 of edema following a series of strokes in London( â€Å"Henry James† par 1). He was the son of Henry, a minister, and Mary (â€Å"Henry James† par 1). He immigrated to England in 1910 and was naturalized in 1915(â€Å"Henry James† par 1). Since he was born in the US he had a similar outlook on perhaps what he wrote about. He moved to London for the latter part of his life, which caused him to see the extreme difference in the European perspective. This is what the novel Daisy Miller is all about. The differences and the controversy that occurs when two different cultures clash together. James had a very successful career that always involved writing. He was a well-known literary critic and novelist. He was a writer for Nation and art critic for The Atlantic in 1866-1869(â€Å" Henry James par 2). He was a writer for the New York Tribune while living in Paris for a year. Surprisingly though he was also a volunteer among the displaced and wounded during World War I (â€Å" Henry James par 2). He received many prestigious awards throughout his life including the Order of Merit in 1915 and he was commemorated with the James memorial stone (â€Å" Henry James par 4). Henry James lived from 1843 to 1916, which is around the same time that he set the period in the novel Daisy Miller. James lived the majority of his life in the US and was raised with the American culture. For the latter years of his life he moved to London were most people were still living in an old-fashioned setting as opposed to Americans who were exploring and expanding from the European way. James having experienced life in both areas causes him to not give quite a clear suggestion on which culture he prefers, â€Å" In late Victorian eyes, Daisy was likely to be either wholly innocent or guilty; James, either all for her or against her†( Ohmann par 1). Due to this the reader is never told which culture James ends up supporting, â€Å" James began writing with one attitude towards his heroine and concluded with a second and different attitude toward her(Ohmann par 1). In the novel Daisy is often regarded as an outsider or an unwelcome intruder in society. Her outgoing and free spirit causes people, specifically Europeans, to look down on her because her behavior does not conform with the norms of that particular society. She stands out but at the same time she does not really care that people are talking about her and looking down on her with distaste. She puts it in the back of her mind and just tells her self that she will do whatever she wants and she will not let anybody tell her that she is not able to. She does not let the fact that she is a woman restrain her from achieving what she wants. Yet at the same time she maintains her dignity and pride while still acting like a woman to a certain extent. She balances the fine line through the book of the quiet proper woman and the wild American. She maintains the free spirit of an American girl, but traditionally she is still a woman who has escorts and fine extravagant dinner parties for young high society people. She revolutionizes the idea that it would be alright to loosen up on occasion, â€Å" her conduct is without blemish, according to the rural American standard, and she knows no other†(Howells par 2). However in the perspective of other people they regard her as a nuisance and someone who is a threat to society because she could soil and corrupt the minds of their young daughters: â€Å" Daisy exemplifies those young girls who have fine social gifts to be sure but whose cleverness is too much for them and if allowed any influence their folly runs away with them, like horses with the bits between their teeth†(Montiero par 4). She stands out and people around her do not appreciate her trying to be different because they do not want to accept change or different cultures. They are all used to the regular routine and tradition that the generations before them have set up and carried out for hundreds of years before them. They expected to continue with tradition for hundreds until they saw things were changing and were scared to approach it so they tried to shut it out. The novel Daisy Miller represents a major problem that is still controversial to this day. Still in the world cultures clash and people are sometimes offended at others. However no one can be blamed because its all about the society’s norms and values. Every society is different and what may be important not one may not necessarily be as important to some one else. Many cultures differ but fortunately they find a common ground to agree upon on the basic rules of society. They may not agree completely but they are willing to acknowledge that its true. Works cited Deakin, Motley F. â€Å"Daisy Miller, Tradition, and the European Heroine. † Comparative Literature Studies. 6. 1(Mar. 1969): 45-59 Rpt. in Literature Resource Center. Detroit: Gale. Farragut High School. 26 oct. 2009 http://go. galegroup. com â€Å"Henry James. † Contemporary Authors Online. Detroit: Gale, 2003. Literature Resource Center. Gale. Farragut High. 22 Oct. 2009 http://go. galegroup. com Howells, William Dean. â€Å" Defense of Daisy Miller. † Discovery of a Genius: William Dean Howells and Henry James. Ed. Albert Mordell Twayne Publishers, 1961. 88-91. Rpt in Short Story Criticism. Ed. Thomas Votteler. Vol. 8. Detroit: gale Research, 1991. 88-91. Literature Resource Center. Gale. Farragut High School. 26 Oct. 2009 James, Henry. Daisy Miller. New York: Penguin Books,1995. Monteiro, George. â€Å"What’s in a Name? James’ Daisy Miller. † American Literary Realism. 39. 3 (Spring 2007): p. 252. Literature Resource Center. Gale. Farragut High School. 25 Oct. 2009 http:// go. galegroup. com Ohmann, Carol. â€Å" Daisy Miller: A study of Changing Intentions. † American Literature. 36. 1 (Mar. 1964):1-11 Rpt in Short Story Criticism. Ed. Anna J. Sheets. Vol. 32. Detroit: gale Group, 1999. 1-11. Literature Resource Center. Gale. Farragut High School. 22 Oct. 2009 http://go. galegroup. com Wardley,Lynn. â€Å"Reassembling Daisy Miller. † American Literary History. 3. 2(Summer 1991):232-254. Rpt in Short Story Criticism. Ed Anna J. Sheets. Vol. 32. Detroit: Gale Group,1999. 232-254. Literature Resource Center. Gale. Farragut High School. 23 Oct. 2009

Human Cloning is Wrong :: Argumentative Persuasive Topics

Human Cloning is Wrong I bet many of you have seen Star Wars, Jurassic Park, Multiplicity, or many of the other movies that describe cloning. Most of what you see in these movies is false. What you don't know if that cloning could be dangerous, to the clone and to our society as a whole. It's unethical to have a human clone. What about identity? Humans are guaranteed the right to their own personality. What would happen if we overrode those rights by giving them someone else's genetic identity? True, personality is not bounded in someone's genes, but the clone would share any physical appearance or genetic defect of the cloned. Also, there is a large power struggle here. Cloning involves a degree of power and control over another person's physical identity and that violates their rights and degrades their unique individuality. The person doing the cloning would have more power than any parent would have. Cloning would also deal with killing embryos. You might not have known, but Dolly, the sheep that was cloned in 1996, was one of over 200 sheep embryos and hers was the only embryo that survived. The rest died or were thrown away. Imagine if the failure rate was that high when we started to clone humans. More than 200 embryos, the start of 200 human beings, would die for the sake of just one embryo that would have the same DNA as some one else. Cloning someone, at this present time, would be extremely dangerous to the birth mother and the clone. In studies done on cows, 4 out of 12 birth mothers died. There is also a very high abnormality rate for the clone. There is a very high failure rate, which is showed in the cloning of Dolly.

Mandatory Drug Testing of Welfare Recipients Essay

Thesis Statement Overall, mandatory drug testing initiatives have noble intentions such as: providing medical care to the abuser, preventing lifelong dependency, and saving taxpayer dollars, however, states should choose to not implement the intrusive testing because it is unconstitutional, costly, and ultimately detrimental to the child, not the parents. Through this presentation you will.. †¢ Learn about how widespread welfare usage is, and the history behind welfare reform. †¢ Understand why some legislators advocate for mandatory drug testing †¢ Look at the facts and realize that it is not only unconstitutional but also not an efficient means of spending allocated funds. Digital image. N.p., n.d. Web. Reasons Why Supporters Believe in Mandatory Drug Testing Overall good of youth dependents Zero tolerance policy Some buy drugs with welfare Tax payers have a right to know That their funds are spent well employed people must take drug tests Overall well being of invidual All reasoning lead to their overall stance, pro-testing. Reasons Why They Don’t Believe in Mandatory Drug Testing th amemmendment) Unconstiutional (4 Cost Prohibitative Embarassing and untimely Potential false positives or false negatives This is why CPS etc. exists Kid gets punished; not the adult All reasoning lead to their overall stance, against testing. Florida Welfare Drug Testing Graphic- DO THE MATH. Digital image. N.p., n.d. Web. Conclusion Mandatory drug testing for welfare recipients is unconstitutional, because no just-cause to search and seize. We must trust that although it isn’t constitutional or affordable to drug test all people, other agencies are other there to protect the children, if abuse or neglect is occurring Correlation does not imply causation. Work Cited Amundson, Kalynn, Anna M. Zajicek, and Valerie H. Hunt. â€Å"Pathologies Of The Poor: What Do The War On Drugs And Welfare Reform Have In Common?.† Journal Of Sociology & Social Welfare 41.1 (2014): 5-28. Academic Search Premier. Web. 5 May 2014 Gupta, Vanita. â€Å"Should Welfare Recipients Be Tested For Drugs?.† U.S. News Digital Weekly 3.46 (2011): 14. Academic Search Complete. Web. 6 May 2014. Lyle, Lindsey. â€Å"Florida’s Legislation Mandating Suspicionless Drug Testing Of TANF Beneficiaries: The Constitutionality And Efficacy Of Implementing Drug Testing Requirements On The Welfare Population.† Tennessee Journal Of Law & Policy 8.(2012): 68-85. Academic Search Complete. Web. 6 May 2014. Work Cited Rhodes, Tim, Sarah Bernays, and Kathrin Houmoller. â€Å"Parents Who Use Drugs: Accounting for Damage and Its Limitation.† Social Science & Medicine 71.8 (2010): 1489-497. Web. 6 May 2014. Vitter, David. â€Å"Should Welfare Recipients Be Tested For Drugs?.† U.S. News Digital Weekly 3.46 (2011): 14. Business Source Complete. Web. 6 May 2014. Vitter, David. â€Å"Should Welfare Recipients Be Tested For Drugs?.† U.S. News Digital Weekly 3.46 (2011): 14. Business Source Complete. Web. 6 May 2014. Wurman, Ilan. â€Å"Drug Testing Welfare Recipients As A Constitutional Condition.† Stanford Law Review 65.5 (2013): 1153-1193. Academic Search Complete. Web. 6 May 2014.

Issues in Scottish Curriculum Design Essay

The way that any curricula is broken up into is two main ways; one being the curriculum in action, where the aims, content and experiences of the curriculum on paper are implemented in practice. The other is the curriculum on paper which is the ideology of what should be implemented in education across the board. The ideology in curriculum can be split up into four main categories. Most papers on this topic, agree to an extent what the four ideologies constitute of, but Schiro’s (2008) ideologies are the most commonly known. The ‘Scholar Academic’, the ‘Social Efficiency’, the ‘Learner Centred’ and the ‘Social Reconstruction’ ideologies are the four main categories explained in the Curriculum Theory that will be discussed in this paper in relation to The Curriculum for Excellence, the current curriculum in Scotland. The oldest of the four ideologies is the Scholar Academic ideology which focuses on the accumulation of knowled ge and understanding. The aim of this ideology is to pass on the knowledge of certain disciplines (subject areas), to allow there to be future scholars in that particular area and therefore, further develop understanding. The academic disciplines are the result of the culture’s compiled knowledge and understanding of each area, and with this in mind, the purpose of education is to assist pupils to learn this knowledge. The next ideology is Social Efficiency. This is pretty dominant in our curriculum today and means to prepare the learner for becoming an efficient and contributing member in society. The learner’s objective is to learn certain skills that will in turn achieve certain objectives that benefit society (Lorrie A. 2000). The individual will learn a mixture of knowledge and skills that can be put together, therefore making the skills more efficient and more beneficial to society. The learner centred ideology focuses more on the needs and interests of the individual rather than the c ontent they are to learn. The idea behind this theory is that learning will take place due to the interactions between the individual and their environment, therefore being more down to the experiences rather than the content. The newest of these ideologies is Social Reconstruction. This is where the social reconstructionists are aware of the problems in society and see the job of the educator to correct these problems in the classroom, hoping that it will reconstruct their society as it is (Groenke, S. 2009). The focus of the curriculum would not be based on knowledge but more of values and opinions that would benefit the society and make it attain the greatest satisfaction of its members. In ‘Building the Curriculum 3: A framework for learning and teaching’ it has examples of all four of the classifications of the curriculum ideology provided by Schiro (2008). It has examples of Academic ideology as it discusses the importance of knowledge and the ability and opportunity to increase the depth of knowledge already acquired as it states â€Å"Throughout a young person’s learning there will be increasing specialisation and greater depth, which will lead to subjects increasingly being the principal means of structuring learning and delivering outcomes.† (page 20, Building the Curriculum 3). From this quote we can relate the academic ideology through the concentration on developing knowledge further to specialisation in certain subjects, therefore being able to pass on the knowledge and allow it to grow from there. There are many examples of ‘The Social Efficiency Ideology’ in the paper as it focuses on health and wellbeing experiences and outcomes where the individual’s get the opportunity to gain skills that benefit the individual in life and work, but also the community around them. This is to help them become effective contributors in society: †¦support all children and young people in developing skills which they will use throughout their life and in their work, including the development of pre-vocational, enterprise and employability skills, personal skills, high levels of cognitive skills and the opportunity to put learning into a practical context. (page 15, Building the Curriculum 3) This example shows that the curriculum is aiming to encourage the learning of certain skills that will improve chances of employability and life skills that will help the young people settle into society and be able to play their part within it. The Curriculum for Excellence sees itself as being centred on the learner, and their individual needs. There are plenty examples throughout the paper of this ideology where the child is involved in what they are learning and setting themselves goals to achieve and having choice in what they learn within the curriculum, â€Å"All children and young people should experience personalisation and choice within their curriculum, including identifying and planning for opportunities for personal achievement in a range of different contexts† (page 17, Building the Curriculum 3). This quote shows that the idea of the curriculum is to give young people freedom to make their own decisions in what they are learning and at their own level. There are four capacities that make up the purpose of the curriculum that are described in this paper. ‘Successful learners’, ‘confident individuals’, ‘responsible citizens’ and ‘effective contributors’, are the capacities that the curriculum aims to enable young people to become. ‘Responsible citizens’ is a good example of The Social Reconstructive ideology as it explains how they will learn respect and about different cultures and how to behave responsibly within the community in all aspects (political, cultural or otherwise). As Building the curriculum states: †¦able to develop knowledge and understanding of the world and Scotland’s place in it, understand different beliefs and cultures make informed choices and decisions evaluate environmental, scientific and technological issues develop informed, ethical views of complex. (page 22, Building the Curriculum 3) Here in this example, it shows that the curriculum wants to provide young people with varied knowledge so that the decisions they make in the future will help to create a better society. The idea is to teach them about values and respect so that they may make better informed decisions as to what is best for the society around them. Building the Curriculum 3 contains examples of all four of the ideology categories, but there are two that are most prevalent, ‘Learner Centred’ and ‘Social Efficiency’. Upon examining the evidence in more depth it seems that the ‘Social Efficiency’ ideology is the most dominant within this paper. Its main focus is on preparing and equipping individuals for future endeavours. For instance, the skills needed for future work prospects upon which Kridel’s (ed.2010) summary, of David Sneddon’s idea of social efficiency, explains the curriculum as a way to make individuals efficient for work. As discussed by Arnoldy (online), social efficiency in education is more for the benefit of the social economy than for the individual, but contradicting that theory in this paper, are the examples of learner centred ideology that is dotted throughout. Though, combining these two theories, Valades’ (online) talks about the idea that to help out society, educating young people to learn and improve their skills and capabilities to help the community in the future, is the way forward. From Building the Curriculum 3 and having summarised that the main ideology behind it is focusing on preparing the individuals to become more efficient and productive for contributing to our society, we can see that there will be some implication for teachers. Teachers who have been teaching for years under the same curriculum will struggle to accept the new curriculum, if it is as completely different way to how they have been teaching before. Although the main focus of the curriculum in Scotland has been focused on preparing individuals for the future, it has not been focused on the more individual level. This may cause implication for teachers as they only have specific allocated times to be with classes and it will be hard to offer each individual, the time and attention they need to develop specific skills to the point of being efficient. The teacher will have to focus more on the experiences and outcomes the learners are objected to, to develop the skills needed for the real world. This causes some problems as it depends highly on what the school can afford to give in ways of experiences, as most of these will probably be met outside of school. So, teachers need to find a way of achieving the outcome of making the individual a more effective contributor to society by combining what they learn in and outside of the classroom. This would be a task for teachers, as the environment each individual they teach will be different and this therefore means that the teacher will have to find a way to combine these different environments or find a similarity and focus on that. Building the Curriculum 3 has some implication for teachers, but the focus being on social efficiency means that in some ways there are not so many changes from the past as at least for the last hundred years the school curriculum has been focused on making learners that will have skills that will help them achieve objectives that will make the society a more efficient place. A Comparative Overview of the Curriculum Ideologies – Chapter 6 http://www.sagepub.com/upm-data/47671_ch_6.pdf (visited 29th dec 2012) Critical Pedagogy and Teacher Education in the Neoliberal Era: Small Openings pp 3 Springer Netherlands, 2009 volume 6 Susan L. Groenke http://www.geocities.ws/rf_valades/index2.htm Social Efficiency Theory – SAVE SOMETHING TODAY Rodrigo Valades visited 29th dec 2012 The Role of Assessment in a Learning Culture Lorrie A. Shepard Vol. 29, No. 7 (Oct., 2000), pp. 4 American Educational Research Association http://www.sagepub.com/upm-data/47671_ch_6.pdf Chapter 6 – A Comparative Overview of the Curriculum Ideologies visited 29th dec 2012 Encyclopedia of Curriculum Studies edited by Craig Kridel SAGE Publications Inc 2010 Pg 4-7 Curriculum Theory: Conflicting Visions and Enduring Concerns, Schiro, M. (2008a) SAGE Publications, Inc Pg 199-245 Curriculum Theory: Conflicting Visions and Enduring Concerns Second Edition, Schiro, M. (2012b) SAGE Publications, Inc Building the Curriculum 3: A framework for learning and teaching, The Scottish Government, 2008

Free Essays on Vincent Price Gallery

Vincent Price Gallery As I am the one who loves the arts, I went to the Vincent Price Gallery. Actually, when I just passed by and saw the sign that said â€Å"To the Gallery†, I was automatically brought by my feet there. As soon as I set my feet on the porch, it attracted me a lot. It was really amazing. It is decorated by white color and used a lot of lights. White color makes it bright and more attractive. Its professionally equipped and maintained facilities are really good. Therefore, it looks like a recently decorated even though it was founded in 1951. The pictures are placed in order. I saw a lot of oil pictures and photograph there. They all attracted me a lot because there are many different style and varsities of interesting such as pictures and photographs. Later, I became to know that all the pictures in the Vincent Price Gallery have been donated by Vincent Price and numerous other contributors. All the art collectors must have a psyche of living in a home surrounded by beauty. In the gallery, I looked all the pieces with great interest. In there, I had a great interest in â€Å"Frankenstein At The Wheel†. It is only a silver gelatin photograph that is presented by Philippe Halsman. Even though it was just a photograph, it had a lot of interest and surprise because one gentleman was driving speedily without looking forwards. At one glance, I was really scary by it because the gentleman in the picture has two faces. One is at the back and it looks like turning backwards. The other is appeared at the front mirror. As I looked at it thoroughly, I found out the face at the back looks like the mask and the face in the mirror is his actual face. The presentation by the photographer successfully gave life to the photograph. I am sure that every one who looked at the photograph was felt the same feeling like me. In the gallery, all the pictures made me have interesting a lot. But the photograph I mentio... Free Essays on Vincent Price Gallery Free Essays on Vincent Price Gallery Vincent Price Gallery As I am the one who loves the arts, I went to the Vincent Price Gallery. Actually, when I just passed by and saw the sign that said â€Å"To the Gallery†, I was automatically brought by my feet there. As soon as I set my feet on the porch, it attracted me a lot. It was really amazing. It is decorated by white color and used a lot of lights. White color makes it bright and more attractive. Its professionally equipped and maintained facilities are really good. Therefore, it looks like a recently decorated even though it was founded in 1951. The pictures are placed in order. I saw a lot of oil pictures and photograph there. They all attracted me a lot because there are many different style and varsities of interesting such as pictures and photographs. Later, I became to know that all the pictures in the Vincent Price Gallery have been donated by Vincent Price and numerous other contributors. All the art collectors must have a psyche of living in a home surrounded by beauty. In the gallery, I looked all the pieces with great interest. In there, I had a great interest in â€Å"Frankenstein At The Wheel†. It is only a silver gelatin photograph that is presented by Philippe Halsman. Even though it was just a photograph, it had a lot of interest and surprise because one gentleman was driving speedily without looking forwards. At one glance, I was really scary by it because the gentleman in the picture has two faces. One is at the back and it looks like turning backwards. The other is appeared at the front mirror. As I looked at it thoroughly, I found out the face at the back looks like the mask and the face in the mirror is his actual face. The presentation by the photographer successfully gave life to the photograph. I am sure that every one who looked at the photograph was felt the same feeling like me. In the gallery, all the pictures made me have interesting a lot. But the photograph I mentio...

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.

Political Consensus Decision-Making Essay Example | Topics and Well Written Essays - 1000 words

Political Consensus Decision-Making - Essay Example Perhaps the most notable instance this mode of political consensus has been implemented is in wartime situations. Within the United Kingdom the 20th century witnessed a major instance of wartime consensus proceeding World War II where it’s argued that consensus politics culminated in the Labour party’s victory. This essay considers that the idea of a wartime consensus culminating in Labour’s election victory fades the closer you get to it. The popular perspective had considered that following World War II the political situation in Britain was such that an overwhelming consensus resulted in the election of the Labour Party. Recognition of this perspective takes into account historical perspectives on the Labour Party. While the Labour Party has been in existence since the early years of the 20th century they assumed great control during the period surrounding World War II. In 1940 the Labour Party returned to government as a part of the wartime coalition; during this period Clement Attlee was appointed the Lord Privy Seal (Pimlott 1994, p. 225). Following the end of the war, the Labour Party contested the 1945 general election and won a large-scale victory. Clement Attlee then assumed control and one of the most radical government’s in British history was instituted. It is this victory that many have contested was the result of wartime consensus. ... mplements a number of notions within this spectrum of investigation, perhaps the central thorough-put of his argument is the contention that rather than constituting an actual consensus, this notion has been constructed by individuals attempting to establish a mythic ‘golden age’ of British history. As noted, this perspective has been embraced by a large number of theorists (Rollings 1994; Kelly 2002; Ellison 1994). The broad spectrums of these theoretical perspectives have considered a variety of ideological differences that occurred between the main political parties during this period. Rather than constituting a golden age of consensus politics, Pimlott (1994, p. 231) notes that there was considerable Conservative hostility towards universal welfare benefits. Kelly (2002, p. 21) considers that in 1956 Anthony Crosland made a large-scale plea for the left to oppose conservative ideas; this is believed to demonstrate a general lack of qualitative accord among political perspectives during this period. Pimlott has extended the situation through metaphorical notions. He states (1988, p. 232), â€Å"sandbagged in their electoral trenches, early postwar voters can be seen as the anonymous infantry of two implacably opposed armies in an era of adversarial politics, with the middle-way Liberals floundering in no man’s land.† To a large degree what Pimlott has established with these notions is a mode of myth-making that seemingly implements higher degrees of fact-based understanding. While Pimlott’s perspectives have gained widespread support there also exists a strong contingent of theorists who hold to the consensus perspective (Kavanagh 1994; Addison 1992). Paul Addison is the theorist perhaps most identified with consensus notions of post-war politics (Addison