Comparing and Contrasting the Movie and Natalie Babbitts Book Entitled

Do you know a book called Tuck Everlasting which is written by Natalie Babbitt existed in this world? It is a very interesting novel with a very sad ending. It’s a story about a girl, who discovered a very dangerous secret about a particular spring water. When you drink the water, it makes you immortal. A movie on this book was produced later on. Things change when you have to audition something that is written. And so, the movie Tuck Everlasting was very different from the book Tuck Everlasting. Winnie Foster, a ten-year-old girl, discovered a very dangerous secret about the spring water in the woods her parents owned. She found out that if the spring water is drunk, it makes one immortal. Winnie didn’t understand what it was like being immortal, until she met the Tucks, who had drunk from the spring water and had become immortal. She wanted to be immortal too, but they talked her out of it, except for Jesse Tuck. Jesse and Winnie liked each other very much. Jesse wanted Winnie to drink the spring water so that she could be immortal and could live with him forever. Jesse told her to drink the spring water when she gets a little older because Winnie was too young to drink it now. Winnie agreed. But in the movie, she turned out to be a fifteen-year-old young adult. So Winnie didn’t need to wait to drink the spring water. It was very surprising to see Winnie as a teenager when we all imagined her being a little kid. Because she was a little girl in the book, immortality was the main thing that was going on. But she was about fifteen years old in the movie, which changed the whole meaning of the book Tuck Everlasting. A movie which was supposed to be about immortality was turned into a romantic film. Winnie Foster and Jesse Tuck ... ...head. When he got to the Tucks house, he told them that he was taking Winnie away and that he bought the Fosters’ woods. Mae was so angry that she killed him. The constable arrived, just in time to see Mae doing that. So, in the book, Mae got into jail but in the movie, both Mae and her husband, Angus, got into jail. Winnie wanted to help them get out of jail. She succeeded in freeing them but used different methods for the book and the movie. So in the book, Mae got into jail but in the movie, both Mae and her husband, Angus, got into jail. Winnie helped them get out of jail but used different methods to free them. I like the reading book better than watching the movie because there are more facts in the book than the movie. Maybe I just like reading books better than watching movies. That’s my opinion. What’s yours (if you’ve read the book and seen the movie)?

Cold Food Festival

1. Cold Food Festival originated from Chinese according to a legend. The legend has been told that, in Spring and Autumn period,  Chong'er  (Tan Van Cong), a prince of Jin, endured many hardships while he fled around the warring states. Once, in order to help the prince who was tormented by hunger,  Jie Zhitui  (Gioi Tu Thoi) cut off the flesh from his thigh and offered it to the prince for sustenance. Later, when Chong'er became Duke Wen of Jin, he ordered a search for Jie Zhitui who had gone into hiding in the remote mountains with his mother.Jie Zhitui had no political ambitions and felt ashamed to work with his hypocritical fellows, hence refused invitation of the Duke. Then the mountain was ordered to be burned down in order to force Zhitui out of hiding. Unfortunately Zhitui did not give in and the fire ended up killing Zhitui and his mother. Filled with remorse, the Duke ordered that each year during these three days the setting of fire is forbidden – all food w as to be consumed cold. Therefore the Festival is thus namedIn Vietnam, because of a thousand years of domination by northern invaders, our people were affected by Chinese customs and we also celebrated Cold Food Festival, which is called T? t han th? c , in the northen part of the country, but only marginally. However, our Cold Food Festival is very different from Chinese’s. We cook  glutinous rice  balls called  Ã¢â‚¬Å"banh troi banh chay†Ã‚  on that day to worship their forefather but the holiday's origins are largely forgotten, and the fire taboo is also largely ignored. 2. Origin of â€Å"Banh troi banh chay† In Cold Food Festival, â€Å"banh troi banh chay† are indispensable.However, through many generations, people still make these cakes but almost of them do not know about their origins. There are many legends about them but the most famous one is the legend of Lac Long Quan and Au Co. According to this legend, Au Co gave birth to a bundle of 100 eggs, which hatching 100 sons. After growing up, a half of the sons followed their father to go to the sea, and another half, together with the mother, went to the mountain. So Vietnamese people make â€Å"banh troi† as the symbol of 50 sons, who hatched from 50 eggs, went to the mountain and â€Å"banh chay† as the symbol of others who went to the sea.Today, we make these type of cake to remind ourselves about our root. Due to limited time, in this part, we just present how to make â€Å"banh troi† and its ingredients. ? Ingredients: – Sticky rice flour – Salt – Water – Candy – Roasted sesame and coconut which is scraped into fibers. ? Process of making cakes: – Mix the flour with salt and cold water, and knead the dough. – All the flour should be mixed gradually; if it’s in excess, add more flour until the mixture is smooth and soft. – To knead the cake, first of all, take small parts of the d ough, roll and then give the dough a slight press in order to flatten.Secondly, put the candy into the middle, and bundle up. – Try to roll them roundly and regularly so that the cake will look good – Before boiling the cakes, you should prepare a bowl of water to drop them into it when they are picked up. – Boiling a pot of water and drop the cakes in turn, just 5-7 cakes one time to pick them all up at the same time. At first, the cakes will sink when we drop them in. – When the cakes are done to a turn, they’ll float, which means it’s time to pick them up. – Remember to drop the cakes into the bowl right after pick them up so that we can prevent them from being sticky. Finally, all you need to do is to pick up the cakes, put them into a dish, and sprinkle the dish with roasted sesame. 3. Meaning: In our country, Cold Food Festival has a profound national meaning which is consistent with the psychology as well as daily life of Vietn amese people. In Cold Food Festival, people only make â€Å"banh troi, banh chay† to replace cold food. Its main aim is to remind us of our ancestors. â€Å"Banh troi, banh chay† are made to express our gratitude and remember our root. On the whole, it is an interesting cuisine festival that not all countries over the world have.

To What Extent Was the Lack of Political Reforms the Main Cause of the 1905 Revolution

To what extent was the lack of political reforms the main cause of the 1905 revolution? The 1905 Revolution was brought about by Bloody Sunday, this attack from the Tsar’s army on innocent peaceful protestors was the trigger for the revolution. Many other reasons throughout the years leading up to 1905 lead to the revolution. To understand fully why the revolution took place you need to understand all of the political reforms or the fact that there were not enough. A main factor contributing to 1905 revolution was the power held by the Tsar, the peasants and workers did not agree with the autocracy that was pushed onto them. Before the revolution all other political parties were banned by the Tsar and were not allowed to form groups that were against the Tsar, any groups that did try to do this, their leaders were either killed or sent to camps in Siberia as political prisoners, this level of harsh treatment towards political opponents and because of this lack of political reform a large amount of resentment was felt towards the Tsar. The lack of a Parliament also left people in Russia pushing for change, and because of this, there was a real need for a reform to create a working parliament so that not all of the power was in the Tsars hands. To stop the 1905 Revolution, the Tsar realised he was going to have to give up some of his power and to try and reason with his people, or this is the picture that he painted with the October Manifesto, this contained some political reforms that relinquished some of his power and some reforms that gave peasants more independence and factory workers better conditions. This manifesto showed a reasonable level of political reform but he did not actually have any intention of giving any of his power up. By deploying the October Manifesto the Tsar actually calmed tempers of his opponents and satisfied them for a time. If the Tsar had stuck to these political reforms there would have been no more unrest through the country but because he went back on them, it in fact worsened the situation and because of the lack of reforms this again led to more and more uprising across Russia. All of the different political parties that started to develop across the country started to socially and economically advance, this was because of more and more middle class people thinking that their voices should be heard. These parties all had many different ideas for political reforms, but first of all they all wanted an nd to autocracy and political change to take place. There was also a major uproar about the Russo-Japanese war which ended in September 1905. This was a huge embarrassment for Russia who were supposed to be one of the great powers in the world and were defeated by an inferior force. This caused much anger throughout Russia because of the Russian people believing that Nicholas II was not able to lead th e country through a war. This was another contributing factor to the uprising of 1905. The loss of the war shocked the Russians and knocked the countries esteem and added to what was already a simmering tension within Russia. In turn this was one of the triggers to the revolution. There was a slight hope that came through with the October Manifesto with the chance of a Duma, but this was short lived, after Nicholas II closed the first two Dumas down after only three months of them starting. This was another case where a political reform that would have made a difference to Russia and helped keep the country under control was not used to its full extent and ended up mounting more anger towards the Tsar for going back on his word. His minister then made it near on impossible for any real threat to the Tsar to be involved in both the third and fourth Duma. During this time there was a huge growth in the industrial industry in Russia and there was a need for political change to be able to get better working conditions in factories. More and more factories were being built and because of the lack of reform leading to the revolution many workers were protesting about their safety, hours and conditions. A real lack of political reform was a main contributor to the 1905 Revolution, although the real trigger was the Bloody Sunday massacre there was throughout the beginning of the 20th century a growing anger and resentment felt towards the Tsar and the way he was leading the country. The reaction of the Tsar in the revolution led to resentment about the reforms in the October Manifesto as well due to him just turning back on them. Overall there was a definite lack of reforms leading up to and after the 1905 Revolution.

kipsy Essay Example

case study ob eric/ kipsy Essay Example case study ob eric/ kipsy Paper case study ob eric/ kipsy Paper case study 0b eric/ kipsy BY Dasoxup Summary of the Facts Eric and Kipsys case study helps to demonstrate the complex nature of management and organizational behavior. The case also shows the difficulty in identifying a single solution toa particular problem. Eric is the new manager of product information for a national firm which wholesales electrical components and Kipsy is a clerk. Eric is appointed the new manager right out of management training. He knows virtually nothing about the people he would be managing or the kind of work they did. On his first day Eric was fascinated by the efficiency of the operations. He soon learned how wrong he was on the second day of work. The salesmen had a list of problems they were experiencing in which they wanted Eric to solve. The three main problems are: Salesmen often were unable to get through quickly to information clerks. Errors were excessive and the clerks were often abrupt and unfriendly to the salesmen when they called. He also noted other problems which came to light which are high absenteeism and turnover, unskilled part time staff, loafing on the Job by the clerks etc. Eric was visited by the regional vice president of the company who informed him hat sales were falling companywide. He then developed an Action Plan to increase efficiency, reduce call in delays and slash the error rate. He seems to be a consultative manager which is shown by his approach to his supervisors and team members by holding meeting to try and address the problems. Disaster struck in relation to his new program in that an employee had defaced two posters used to motivate employees. His lack of experience is shown with his failure to take control of his supervisor in respect of the discipline to be maintained within the office. He eeded to take his supervisors to task over their failure to deal with the posters immediately. Eric pondered his dilemma and he concluded that the key to his problems was KIPSY. Kipsy has been an information clerk in Erics office for almost a year. In that year she has become increasingly frustrated and unhappy in her work. Kipsy had applied for the Job at the company because a friend told her that the company was a great place to work, the pay was excellent and the people she would be working with were friendly and stimulating. It was also known that the company was growing and expanding at a fast clip. To Kipsy that meant that there was a good chance for advancement which was very important to her. After a few weeks on the job her optimism and excitement was replaced by frustration and disappointment. Many of her new friends were quitting and none of the clerks knew of anybody who had been promoted to management or a better Job from the ranks of console operators. Kipsy decided the only good thing about her Job was that of becoming the informal leader of the work group. Kipsy was excited when she heard about the new manager who seemed genuinely interested in learning about the Job and in hearing hat changes people had to suggest. Her opinion about Erics managerial abilities dropped sharply a few weeks later mainly because of by what came to be known around the office as the flexible hours fiasco. She spoke to Eric about the possibility of advancement in which she did not receive a favorable response. Her expectations of the bright new manager were dashed which leads her into dysfunctional behavior. system. It took the Increase Efficiency program to finally break KIPSY completely. She and another co-worker defaced the motivational posters. Kipsy felt guilty after she had defaced the posters. Frustration is the main cause of her behavior as she recognizes that her actions were wrong but she can see no way of redressing the situation. Statement of the Problem The company has been experiencing a fall in sales which is a result of internal organizational problems. Listed below are the main problems identified: High Turnover and Absenteeism Kipsy Low customer satisfaction Lack of Communication High turnover and Absenteeism On a daily basis, employees were given a task to operate the consoles by providing the sales men in the field with information about a particular item from the catalogue. This work was monotonous and became very boring for the workers. Although the pay was good, they werent motivated to do the same monotonous task daily, so their Job involvement decreased. Absenteeism is becoming a major problem to Eric and the business due to the fact that 15 to 20% of the clerks were unlikely to show up for work on any given day especially Monday to Friday. Employees would develop a habit of tardiness, and the turnover rate was very high because 80% of employees on the Job quit every year. Kipsy- Kipsy had emerged as one of the informal leaders of the workforce. She had he power to influence the other employees , teaching them creative ways to loaf on the Job; such as ways to busy out their consoles and appear as if they we were being productive on the Job when really they were not. Kipsy displayed employee deviance by trying to undermine Erics attempts to better the organization; she targeted the signs he had put up around the office changing Increased Efficiency to Increased INEfficiencY. Low customer satisfactions Customers were unsatisfied with the service as they were always kept on hold for a long time. They were always promised to get their tems on a specific date and time which almost never happens. Customers are always complaining that the material had not been delivered and the price was different from the one which was quoted to them. This can be seen as a major problem in relation to the clerks in that the salesmen also complain that the clerks are responsible for relaying the information to them in which most times it is incorrect thereby causing low levels of satisfaction in customers. Lack of communication- The clerks are very disrespectful and unfriendly to the free which has led to communication dilemmas with the salespersons as well as elays in salesperson getting through to the clerk. Eric tried to convince the regional office to give him the authority to introduce a flexible scheduling plan however he had been told that 8:30 to 5 are the available hours Just like any other personnel policies. Eric could not communicate this information to his employees so he solicits Kipsy to tell the others. A list of organizational and managerial problems has also been identified. These includes boredom, clerks not being held responsible for their errors, little chance of advancement, management relying too much on formal structure, lack of nvolvement/participation of management with staff, low levels of motivation, delays in salesperson getting through to clerks, excessive errors, abrupt and unfriendly telephone manners, management failure to motivate staff for example no rewards for good work, low Job satisfaction, inflexibility of management for example working hours, falling sales, The main cause was due to the un-productivity caused by Kipsy being an informal leader within the organization. Her fellow workers looked to her as their leader and did whatever she asked of them. Causes of the Problems Absenteeism When people start missing work on a regular basis, it means that they do not really enjoy what they are doing or they are not motivated to work. This lack of motivation reduces Job involvement which decreases the overall quality of work. High Absenteeism and turnover can be seen as a motivational issue. There are no motivational factors for the employees, which would make them become vigorous in action. A theory of motivation can be used in this case. It is probably safe to say that the best known theory of motivation is Abraham MasloWs hierarchy of needs. According to Maslow employees have five levels of needs physiological, safety, (lower order needs) social, Esteem and self actualization (higher order needs). In this case employees lower order needs are satisfied therefore Eric needs to motivate the clerks by fulfilling their higher order needs. The company needs to motivate the employees by following this level in allowing easier and more opportunities for employees to attain higher positions and expand the possibility for growth in which they are not willing to give their employees. What do the clerks want from their Jobs? In this case the clerks are looking for intrinsic factors as explained by Hertzberg in the two factor theory. These factors include advancement, recognition, responsibility and achievement which are definitely missing from the company. In his theory he cited extrinsic factors such as supervision, pay, company policies and working conditions which lead to dissatisfaction in employees. Despite the four managers not functioning effectively and the pay not was not great but they got increases every year, this was not the focus of the clerks dissatisfaction. Dissatisfaction can be seen n the clerks behavior as a result of the company policy, where clerks wanted flextime and it was turned down by management. Another cause of dissatisfaction is working conditions which were not difficult but monotonous which led to boredom. This dissatisfaction has led to the high turnover rate and absenteeism. MasloWs cause of the companys problem of High absenteeism and turnover. Kipsy Kipsy had self efficacy because she saw herself capable of performing tasks at a higher level. Kipsy was the informal leader however Just like any other clerk Kipsy needed to be motivated to give her best. Kipsy not receiving what she expected from the company has caused her to become deviant thereby creating some of the problems the company is presently facing. The ERG theory states that there are three groups of core needs: existence, relatedness and growth. In relation to Kipsy, her existence need is already catered for. Relatedness She wanted to maintain the relationship of the other clerks who look up to her as an informal leader. Growth She had an intrinsic desire for personal development. Moreover, the theory has a frustration-regression hypothesis, suggesting that individuals who are frustrated in heir attempts to satisfy one need may regress to another one. For example, Kipsy was frustrated by the lack of growth opportunities in her Job and the slow progress toward career goals which caused her relatedness needs to increase by spending more time socializing with the other clerks. The implication of this theory is that we need to recognize the multiple needs that may be driving Kipsy at a given point to understand her behavior and motivate her. Low Customer satisfaction Further we learnt in the case that there was a major problem of customer dissatisfaction. Therefore, the main reason why the rganization has a low level of customer satisfaction is due to the fact the employees are not being productive at work. Lack of communication Excellent communication skills are essential for good performance management. They are important skills used in the entire management process from planning and communicating work expectations to recognizing employees for their successful achievements. In this case it can be clearly seen that there is a lack of communication between the information clerks and the sales men also Eric and the clerks. As we learnt in the case when employees felt overwhelmed ith the work they would busy out their consoles so customers will not get through to them. This has resulted in an overall fall in sales. Lack of leadership, undertrained part time clerks, limited feedback and employees disengagement are poor communication methods which had led to many of the problems the company is facing. Eric has failed to relay on a number of messages or information which has caused low Job satisfaction among employees. The existing communication system was Just downward; this was a problem because of its one way nature. Managers inform employees but rarely solicit their advice or opinions. This was seen when kipsy proposed pre-scheduling working hours to Eric in which he stated the people upstairs wont let us do it. For a company to be successful, information needs to flow in both directions, from top to bottom and from bottom to top. A 2006 study revealed that nearly two-thirds of employees say their boss rarely or never ask their advice. The study noted, Organizations are always striving for higher employee engagement, but evidence indicates they unnecessarily create fundamental mistakes. People need employee suggestions, a practice the company thinks is especially important to nnovation. Possible Solutions This can include change in overall management structure, improve communications which includes staff involvement and meetings, review training program for part time staff, try to change company policy on flexible working hours, review supervisory roles, incentive schemes (not necessarily pay), meetings between clerks and salespersons. Recommended solutions and its implementation Eric needs to be aware of individual differences when communicating with the employees. He needs to spend more time with workers and try and understand their concerns and needs. Be up-to date about any issue and deliver the clerks problem to top management and push them to take action. Eric should give feedback. Although he has spent a modest amount of his time with his employees we have not seen him giving any feedback to them. He can give oral feedback to encourage the employees rather than let kipsy take the role. If we want to examine why high absenteeism and employee turnover rate, low customer satisfaction, lack of communication and Kipsy are problems we have to look at motivation. The clerks and salesmen are not motivated to work as it is reflected in the poor performance as they are not happy in heir Jobs. See below some suggestions to motivate the employees: Recognize individual differences Everyone in the organization has their own abilities to perform a specific task efficiently therefore clerks and salesmen should be rewarded based on their performance. This will motivate them to increase productivity and reduce absenteeism and turnover. Match people to Jobs Choose the right person for the right Job. This is a managerial problem especially HR as it is not appropriate to employ people with good abilities and potential in the call center as in the example f KIPSY. Increase work quality The quality of work must also be improved. Every time a wrong code is typed into the computer and wrong information is given a customer is left dissatisfied. This could be improved by designing shorter number, letters to type and also it would be easier for the clerks to remember. Eric should adopt one of Henry Mintzberg ten management roles which is the role of : Disseminator. To be a good disseminator you need to know how to share information and outside views effectively, which means that good communication skills are vital.

Discussion Worm and Wormwheel Essay Example

Discussion Worm and Wormwheel Essay Example Discussion Worm and Wormwheel Paper Discussion Worm and Wormwheel Paper Essay Topic: Discussion The worm and worm wheel is a very important mechanism in the field of Mechanical engineering. It has the ability to lift heavy loads with very little effort and keep the load raised and locked in a desired vertical position without any effort. The main objective of this experiment was to investigate the behavior of the worm and worm wheel gear set. Unfortunately, all the objectives of this experiment werent fulfilled in this session due to the following factors: The experiment was done only using a single starter worm The experiment was done by using only one gear which had 40 teeth. The apparatus was recently repaired and consequently, it affected the experiment results to a certain extent. However, the experiment was fully conducted for a single started worm in mesh with a 40 teeth gear set. To start the experiment, the effort pulley and the load drum were loaded with appropriate weights and wound. After the weights were loaded, a small downward pull was given to the effort hanger in order to overcome the static friction. It was advised that this manual downward pull should be given by the same person and the Orca should be the same throughout the whole experiment since it could affect the experiment results adversely if done otherwise. And it was also advised that when releasing the effort, the effort hanger should be released from the same vertical height. Although the reason for this is not fully explainable, it can be assumed that this was either because the surface nature of the effort cord was not uniform or due to the number of rotations of the effort cord on the effort pulley that caused a slight difference in the friction between the cord segments. After the experiment, readings for Applied load and Actual effort were obtained and tabulated. The tabulated data was then plotted to obtain a graph after further calculations. The graph was drawn for Actual effort (EAI) vs.. Applied load (F) to find the Law of the machine. During the experiment, there were few conflicts in opinions. Instances for such discrepancies were when at some attempts, the effort was able to lift the load with a mass very low than expected. The reason for this phenomenon is also not completely explainable since physical concepts such s static and dynamic friction are still not quite clearly understood. But it could be assumed that this was due to human error because the initial downward pull was applied manually and there was a chance that the pull was not uniform in all instances of the experiment. In this worm and worm wheel gear set, the machine may not provide a continuous efficiency for all loads since there is a limit to its efficiency. The limiting efficiency for this apparatus can be termed as the reciprocal of the product of the velocity ratio and the slope of the graph drawn for the Law of the machine.

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.

Presidential Election 2012 Paper Essay Example | Topics and Well Written Essays - 1000 words

Presidential Election 2012 Paper - Essay Example In terms of social conservativeness, I consider myself very accommodating and adaptive to change happening in the contemporary society. My political formation was heavily influenced by my high school history teacher. He presented an objective account of the issues that America has faced since its birth, bringing the realization that we have mostly been dealing with the same issues over the years: racism, immigration, gender issues and military action among others. This has helped me analyze the positions taken by different individuals/parties over time and their consequences, providing a basis for most of my political beliefs and inclinations. A number of issues define the current political dispensation in the USA mainly revolving around employment, education, environment, foreign affairs, poverty, taxes, immigration, and healthcare. These issues affect all aspects of the American society and have been the main points of contestation that have decided most of the recent elections. Personally, I feel that the issue on healthcare could be a key deciding factor among the Republican candidates and their choice candidate’s face-off with Obama. Hence, I will focus on healthcare based on analysis of the candidates’ positions in relation to my own views. Newt Gingrich reckons that the current government’s big spending on healthcare should be done away with. Instead, Gingrich proposes a â€Å"Patient Power† plan with the aim of saving lives and cutting costs. He seeks to promote choice among Americans in their healthcare tax cuts, giving the elderly an opportunity to voluntarily choose more personal hea lthcare in the private sector and allowing states to flexibly Medicaid to promote healthcare among the poor (Newtgingrich.com 2012). Ron Paul seeks to promote freedom rather than force in promoting healthcare. He proposes the repellation of the