The TRUenergy Company

The Agents of Erosion

The Agents of Erosion The process known as weathering breaks up rocks so that they can be carried away by the process known as erosion. Water, wind, ice, and waves are the agents of erosion that wear away at the surface of the Earth. Water Erosion Water is the most important erosional agent and erodes most commonly as running water in streams. However, water in all its forms is erosional. Raindrops (especially in dry environments) create splash erosion that moves tiny particles of soil. Water collecting on the surface of the soil collects as it moves towards tiny rivulets and streams and creates sheet erosion. In streams, water is a very powerful erosional agent. The faster water moves in streams the larger objects it can pick up and transport. This is known as critical erosion velocity. Fine sand can be moved by streams flowing as slowly as three-quarters of a mile per hour. Streams erode their banks in three different ways: 1) the hydraulic action of the water itself moves the sediments, 2) water acts to corrode sediments by removing ions and dissolving them, and 3) particles in the water strike bedrock and erode it. The water of streams can erode in three different places: 1) lateral erosion erodes the sediment on the sides of the stream channel, 2) down cutting erodes the stream bed deeper, and 3) headward erosion erodes the channel upslope. Wind Erosion Erosion by wind is known as aeolian (or eolian) erosion (named after Aeolus, the Greek god of winds) and occurs almost always in deserts. Aeolian erosion of sand in the desert is partially responsible for the formation of sand dunes. The power of the wind erodes rock and sand. Ice Erosion The erosive power of moving ice is actually a bit greater than the power of water but since water is much more common, it is responsible for a greater amount of erosion on the earths surface. Glaciers can perform erosive functions - they pluck and abrade. Plucking takes place by water entering cracks under the glacier, freezing, and breaking off pieces of rock that are then transported by the glacier. Abrasion cuts into the rock under the glacier, scooping rock up like a bulldozer and smoothing and polishing the rock surface. Wave Erosion Waves in oceans and other large bodies of water produce coastal erosion. The power of oceanic waves is awesome, large storm waves can produce 2000 pounds of pressure per square foot. The pure energy of waves along with the chemical content of the water is what erodes the rock of the coastline. Erosion of sand is much easier for the waves and sometimes, theres an annual cycle where sand is removed from a beach during one season, only to be returned by waves in another.

A chance meeting and exciting news Essay Example | Topics and Well Written Essays - 1250 words

A chance meeting and exciting news - Essay Example A critical assessment of both options is necessary before the declaration of the decision. Primarily, the first question to address is the money issue. Is the new venture more lucrative than the current position? A critical analysis the remuneration offered here shows that for the first year, working with the partners as consultants would be more financially satisfactory. When the $50,000 is shared equally, the annual salary will be $200,000, which is $50,000 more than what Engulf and Devour are offering. However, this is only assured for the first year only. What happens in the second year if there are no clients? Regardless, comparing the $200,000 offer to the $150,000 provided by Engulf and Devour, the former seems more promising since both opportunities have various uncertainties. Taxation is a key consideration as well. With the partnership being a registered entity, the aspect of double taxation is a partner’s financial obligation. With this consideration, the payment promised by the partnership is much lower after taxation as compared what Engulf and Devour are offering. However, the partnership has a more promising financial future as compared to the job and Engulf and Devour. With the possibility of getting bigger clients, as the reputation improves, the promise of better incomes is higher in the case of the partnership as compared to the current job (Lee 109). Financial concerns are the primary concern for any aspiring entrepreneur. After the financial consideration, the next aspect to take into critical account is assessing the uncertainties of the current contract. What would happen if the contract were to be terminated before it was mature? Likewise, considering the terms of payment is equally crucial. Some clients prefer to pay after the completion of the contract, or on a monthly basis. When handling one’s own business, uncertainties are greater as compared to being employed. Assessing the

What is the one finance related experience or extracurricular activity Essay

What is the one finance related experience or extracurricular activity that is most important to you and why - Essay Example In addition, it provides useful information to investors willing to inject funds into the market through stocks. The comparison also allows one to understand how healthy competition should be maintained to prevent both consumer and business exploitation. One of the most common events that take place in the finance industry is the buying and selling of stock. The companies trade shares and stock in order to improve their financial status and portfolio. The purchase and sale of stock is one of the supplementary activities in finance. I also researched data on each company individually by looking at their financial statements to analyze net profit, loss and ability to break-even. The process is useful in analyzing internal profits, especially how the company got to that level. The University Finance Association has not only been beneficial, but also eye opening. It has enhanced my critical and analytical skills by allowing me to compare companies. As a result, I can make suitable investment

Extra 1 Essay Example | Topics and Well Written Essays - 500 words

Extra 1 - Essay Example Apart from that they reflect the particular era and time during which the play took place. The scene designer designs the background of the play with the colors that bring out, the right texture and desired mood to the audience. As the play unfolds Tartuffe succeeds in convincing Orgon to allow him to stay in his house indeterminately. He is opportunistic as he manipulates the allegianceaccorded to him by Orgon to manipulate him to his own advantage. He starts his schemes by pretending to be a staunch Christian and managed to fool Orgon to believing on every word he said (Steiner and Wilbur 35). Tartuffe tries to seduce Elmire, although she is frustrated by the foolishness of her husband, she does not give in to his advances. Unsuccessful he convincedOrgon to terminate the engagement of his daughter to a young man called Mariane whom she is madly in love with. The daughter refuses to get married to this hypocrite, but she is in a dilemma because she believes that a daughter should obey her father (Steiner and Wilbur 55). The maid, who is convinced that Tartuffe is only after the family’s fortune,makes sure that Valà ¨re and her lover are back together.In the play she is the only one who sees through Tartuffe’s malevolence right from the start. She turns out to be a very intelligent character in the play although ironically the maid is perceived to be a very insignificant job in the society (Steiner and Wilbur 95). Paradoxically the church is misrepresented by the character of Tartuffe who turns out to be one of the main characters in the play. The actors try to bring out the theme of the play strongly by mastering the lyrics and context. Although they have the challenge of being inexperienced, they also manage to bring out the character traits of the key thespians. Conversely it can be observed that there is poor coordination between the actors, when they are in the stage

Case Study Of Yellow Auto Company Commerce Essay

Case Study Of Yellow Auto Company Commerce Essay As one of the most well-known car company, Yellow Auto Company was built in 1989 and occupied 54 marketing share in 2008. Why can it develop so fast and increase their share great in less than 20 years? This paper aims to conduct the case study of Yellow Auto Automotive Company, from the perspective of psychology digging the decision making issues in this company. First, a brief introduction of the company is given to let readers know the basic information of Yellow Auto. Then the relevant decision making issues are analyzed combining the theory of psychology in making decision. At last, suggestions on how to maintain long and short comings of Yellow Auto are given and how to improve their decision making in the future is also discussed. introduction of the Company Yellow Auto Automotive Company was built by two brothers, Can and Caner Sale in 1989. As a family company, its shareholders are acted by the owners and the assets came from the two brothers family. Yellow Auto owns two stores in Gaziemir and Cambidi respectively and acts as one of the most well-known car company over the worldwide. Yellow Auto aims at selling famous brands cars in different areas, such as Coca-Cola. They have two options of car market, first of which are high market demand models and second are those cars with special features according to customers needs. Yellow Auto followed the development step and changes of the parent company. All the employees are required to adapt to the developing steps of technologies. The top manager put eyes on three important departments: finance, sales and after-sales services. The sales of Yellow Auto were supervised by a manager and they put a lot of attention on the face-to-face communication to attract customers. In their recruitment, Yellow Auto prefers active and highly-educated young people. Employees are required to ask every detail and not encouraged to make decisions by themselves. Many rules in the company management are unwritten but stored in hearts of the family members. Yellow Auto always cares about the level of customer satisfaction. They figured out several ways to increase customer satisfaction. They made great effort to attract future young customers, and offered sufficient communication with existing customers, such as telephone conversations and sending text message. Analysis on the Relevant Decision Making Issues in the Case 3.1 Relevant Decision Making Issues What kind of issues in the case Since 2001, top managers of Yellow Auto made a risk decision under the background of a serious economic crisis in Turkey. In the whole changing process, top managers made a lot of analysis on the psychology of employees. They even asked external consultants from a university in Turkey for help to assist the policy change process well operated. Therefore, this report is going to conduct the case study of Yellow Auto from the perspective of psychology. What decisions made /how the decisions implemented by the company Yellow Auto used to make several decisions in the whole changing process as the following. First, top managers of Yellow Auto made the important decision, that is, to achieve a goal of having 50% of the market share in the field. It is a high risky decision due to the economic crisis. In order to promise the smooth going of this decision, Yellow Auto decided to ask help from academics in university. Under the guidance of the external consultants, change efforts are put on increasing physical working conditions, distinguishing tasks for managers and employees, designing careers plans for young generations, and right person for the right job principle. Next the implementation of these decisions by the company will be analyzed from the perspective of psychology theory. According to the transactional analysis by Berne (1961), the human psyche consists of three ego states: parent, adult and child. Yellow Auto Company acts as the adult state. They owns strong objective and always are able to evaluate and critique. When implementing the decisions, top managers evaluate the results in time, face the actual effect of the changing process and make enough adjustment to make sure correct changing direction Whats the result After two years changing process under the suggestion from academics, the job satisfaction and organization loyalty of employees in Yellow Auto are enhanced greatly. The following increased profitability of the company is 25% more than the profitability result of 2001. Yellow Auto also extends their sales and added two stores around lzmir. In the future, the owners of Yellow Auto would maintain the good results and continue the investing in human resources. Through the cooperation with a university in lzmir, human resources of Yellow Auto will have a bright future and bring more good results. Evaluations on the Issues and Decisions How important are these issues and possible influences of these issues People are often sort of reluctant in making decisions. Analyzing the psychology of decision making for managers in company is so important that the decisions by owners and top managers would determine where the company is going to. If top managers made the wrong decision, not only huge crisis will be brought to the future of company, but also the morale of employees and loyalty to the company may be affected greatly. There are several psychological approaches for the analysis of decision making, such as psychoanalytic, behaviourist, humanist, neurobiological and cognitive (Lecture 7). In this report, the psychoanalytic approach will be applied on analysing psychology of decision making. Next, the changing strategy of Yellow Auto will be looked into from the psychology of the decision maker. According to Lauent and Kapferer (1985), there are four factors influencing individuals decision making: sense of oneself, perceived risk, social factors and hedonistic factors. These factors are not only suitable for the consumers, but also fitful for decider (Berne, 1964). On the consumer level, if people are willing to buy products from Yellow Auto, they must seek a feeling of satisfaction. All human beings own the potential of hedonistic factors. Good services and products can help consumers obtain superiority and good sense for themselves. Although perceived risk may exist in their mind, face-to-face communication by staff in the company will assist vanishing the risky feeling, such as employees in Yellow Auto. They are required to contact with consumers by phone calls and message, that gives consumers a family feeling and trust the company increasingly. As top managers, the y must be familiar with the psychology of consumers for better management and marketing future. On the other hand, from the perspective of managers in Yellow Auto, they are also decision makers. They made important decision for the company development. Sense of self is crucial for the top managers and shareholders. Based on their experience in the car market, they may be able to sense sensitively where the big fish is. However, 50% of the marketing share is such a huge risk based on the background of economy crisis. A smart manager should be able to put a lot of attention on the perceived risk and conduct some action, such as top managers of Yellow Auto. They asked help from academics in a local university, that is, they used social factors which can be reached to guarantee their company changing process. Those external consultants were professionally good at analysing psychology of employees and provided managers good suggestions to increase the satisfaction and commitment of employees. From the excellent results of Yellow Auto, that is, they had 54% marketing share in 2008, p sychology of employees and managers play crucial rules in the marketing strategy. Strength and weakness of the decisions made in the case Pisharodi and Langley (1990) used to propose a Perceptual Process Model, assisting the analysis on perpetual process in the decision making. That model consists of three parts: selective attention and emotional maker response, perceptual organization and interpretation, and the attitude and behavior. The Perceptual Process Model is going to be used to analyze the strength and weakness of decisions made in this case. First, under environmental stimuli, selective attention and emotional maker response are made (Pisharodi and Langley, 1990). That depends on a lot of factors, such as characteristics of the perceiver, assumptions and anticipation of future events. One strong strength point of Yellow Auto is that their top manager did well in this step. They perceived the right marketing trend and anticipate a bright and feasible goal for the company. Next step is the perceptual organizaiton and interpretation. An important part is the mental process in it. Here the perceivers or managers should do the categorical thinking and perceptual grouping to make sure the feasibility of the assumption and anticipation. Top managers in Yellow Auto did the perceptual organazation and interpretation so that they obtained the results, that is, they cooperated with academics to guarentee the smooth going of the change. It is indeed one strong point in this case. However, each coin has two different sides. There are still some weaknesses for Yellow Auto. Their main point is focused on the psychology of the employees and they aimed to increase the job satisfaction and commitment of employees. Although the good morale and loyalty of employee are important for the company development and culture forming, it is vitally dangerous if all top managers attention is focused on the psychology analysis of employees. They ignored to put more attention on th e marketing wave and flexible future. If marketing would suddenly change, all the previous work could not be efficient anymore. On the other hand, the competitors of Yellow Auto may be aware of this weak point of the company and attack Yellow Auto when the marketing is changing. If Yellow Auto is still paying attention on the psychology of managers and employees, but not to figure out strategies to face the changing market, Yellow Auto would be in big trouble. After these two steps, Yellow Auto come out the attitude and behavior which is the last step of the Perceptual Process Model. Recommendations advices on ways of maintaining advantages and facing challenges ¼Ã¢â‚¬ °and how to improve their decision making in the future From the results of the change in Yellow Auto Company, they indeed did a good job; however, it still has the points to be improved. Here this report is going to give some advices on maintaining the advantages and how to improve their decision making in the future. First, Yellow Auto should continue with their adjustment which maintains the current job satisfaction and commitment of employees. From the experience, increasing morale of employees indeed help people treat the company as their own family, so that they would take 100% effort for working. Also, the recruited personnel for the the right person for the right job should be continued. That saves a lot of time for both managers and employees. From the psychology perspective, this change to some extent increases the morale and loyalty of employees. People can sense the feeling of being valued and nobodys talent would be wasted in some meaningless position. However, there are various sources of perceptual process bias that deserve more attention (Zajonc Nieuwenhuyse, 1964). These perceptual process should be put enough attention by Yellow Auto. They may be able to slow down the development of the company. For example, the attribution error easily leads to the perpetual process bias. All human beings tend to see the favorable point as the future result. Actually that is rather dangerous. If top managers of Yellow Auto were with the attribution error, they would fail to anticipate the actual direction of marketing, so that they may not be able to make the very first decision, that is, a goal of 50% marketing share. Another serious perpetual process bias is recency effect (Broadbent, 1967). Thats why top managers in one company should have long distance insight, and be able to avoid the garble brought by some fancy recency effect. Last but not the least, Yellow Auto should put more attention on the marketing wave and possible change. Although the good morale and loyalty of employee are important for the company development and culture forming, it is vitally dangerous if all top managers attention is focused on the psychology analysis of employees. Then other competitors would seize this opportunities to occupy the good marketing. The huge loss can be hardly saved by psychology. Conclusion This paper aims to study the case of Yellow Auto Automotive Company, from the perspective of psychology to investigate the decision making issues in this company. First, a brief introduction of the company is given to offer the basic information of Yellow Auto. As one of the most well-known car company, Yellow Auto Company was built in 1989 by two brothers and occupied 54% marketing share in 2008. Yellow Auto used to make several important decisions in the whole changing process. This report analyzed the implementation of these decisions by the company from the transactional analysis perspective. Next, the changing strategies of Yellow Auto are looked into from the psychology of the decision maker. And the strength and weakness of the decisions made in this case are analyzed based on the Perceptual Process model. One strong strength point of Yellow Auto is that their top manager did well in perceiving the right marketing trend and anticipating a bright and feasible goal for the compa ny. However, their main point is put on the psychology of the employees and they aimed to increase the job satisfaction and commitment of employees. They ignored to put more attention on the marketing wave and flexible future. If marketing would suddenly change, all the previous work could not be efficient anymore. At last, suggestions on how to maintain long and short comings of Yellow Auto are given and how to improve their decision making in the future is also discussed. Yellow Auto should continue with their adjustment which maintains the current job satisfaction and commitment of employees. And the recruited personnel for the the right person for the right job should be also continued. However, there are various sources of perceptual process bias that deserve more attention, such as attribution error and recency effect. And Yellow Auto should put more attention on the marketing wave and possible change.

Intertextuality Essay -- essays research papers fc

What is intertextuality? How does intertextuality challenge E.D. Hirsch’s idea that a text has a single meaning created by its author? Explain with reference to examples drawn from any media format. According to American literary critic, E.D. Hirsch, in order to interpret a body of text, one must ask one’s self the only question that can be answered objectively – â€Å"what, in all probability, did the author mean to convey?† He believed that the author’s intended meaning equates the meaning of a text and it is in fact, the reader’s duty to uncover the the author’s intentions. â€Å"The meaning of a text and its author’s intentions are one and the same.† Hirsch’s concept revolves around the assumption that a body of text is original, and is purely a body of the author’s sole â€Å"intentions†. The production of text, if one were to adhere to Hirsch’s theory, is therefore exclusive to the author’s own ideas and concepts and free of external influence. However, the notions of langue and parole disputes this idea. According to Barthes in 1984, â€Å"It [la langue] is the social part of language, the individual cannot himself either create or modify it†. Furthermore, Ferdinand de Saussure’s work on structuralism and semiotics demonstrates the subjectivity of language and can be said to have sewn the seeds for modern concepts of intertextuality (such as those developed by Roland Barthes and Julia Kristeva). Intertextuality challenges the idea of a text’s ability to be truly original and therefore disagrees with Hirsch’s theory. In this essay, I will focus on how conscious intertextuality as well as the semiotics involved in unconscious intertextuality both dispute the idea that the meaning of a text belongs exclusively to its author’s intentions. Julia Kristeva, who was the first to use the term â€Å"intertextuality†, proposed the idea that a text should not be interpreted merely by its words at face value, but also studied based on other works it has adapted and was influenced by. The concept can be further expanded upon by Gunther Kress’ notion of â€Å"ceaseless semiosis† which brings to light the social aspect of a text’s creation. â€Å"From the beginning, I use materials which I have encountered before, which bear the meanings of their social contexts, to weave a new text which, because it is woven from materials of other texts, everywhere and always connects with those other te... ...mpaigns, can now be seen as the qualities Bridget desires by smoking Silk Cut. Once again, Hirsch’s idea of a text bearing only one singular meaning can be easily disputed. The interpretation of the Silk Cut advertisement, as well as the use of Silk Cut cigarettes in Bridget Jones’s Diary, is highly subjective and dependent on the reader’s cultural literacy and existing knowledge. Intertextuality in the media, both print and otherwise, has become too powerful to ignore, especially in this day and age. The internet, satirical texts, advertisements and books are only some examples that demonstrate the effects other works and a reader’s prior knowledge have on any given text. Intertextuality in its various states, conscious and unconscious, is certainly a valid contention against the theory of E.D. Hirsch. Bibliography, References & Notes 1) Cultural Consumption and Everyday Life†, Reading As Production, John Storey, Pg 63, Arnold, London, 1999 2) Intertextuality, Allen.G, Pg 9, Routledge, London 2000 3) http://web.uvic.ca 4) http://www.theonion.com 5) http://www.geocities.com/howtodressemo 6) http://www.aber.ac.uk 7) Reading Ads Socially. Goldman. R, Routledge, London, 1992

ICT †Business Use Essay

About the Business I’ll use ‘Ki for hair’ as a basis of my project. This is a hairdressing salon in Camden Town, where Myra Ferreira keeps her own business. She is the manager of the salon, although there are two more workers (hairdressers). I worked there last summer (2002) and I know how they manage their entire budget on paper base. She started with a small business two years ago and still keeps all her income and expenses manually. Every hairdresser has a minimum of three clients per day usually, which means about 270-300 clients per month. The situation now To keep all the paper work, safe and in order they need a separate room. It takes a day for two people to produce the monthly reports, which means they lose about 6 clients a day (12 clients every month). The monthly report itself is working out the income and expenses and therefore the profit and producing it clearly for every single month. Although it is going fine, the business is getting bigger and needs a system, which makes the budget more accessible, produces clear reports for the tax purposes and takes less time to be done. How the ICT can help Computers have many applications in the 21st century. Specific software such as databases and spreadsheets are designed to help, improve, speed up and reduce the workload of certain tasks. In order to help them I’ll use the ICT (Information Communication Technology) to create a system, which will work out the budget easily, will be more accessible and will take less place, as well as time to be managed. ICT develops every day and replaces more and more the manual work. As everything else it has its advantages: takes less space, time (one person will need about half an hour to do all the work, which means more clients and more income) and effort to be accessed. The disadvantages are that only people with certain skills can do the work. I’ll try to transfer this disadvantage into advantage for the users, as they will learn how to manage a computer system. The Solutions One of the solutions is using just a word processor for producing the information, and calculating the budget separately. That’s is going to work perfectly fine, but will take much time. Other solution is to use just Microsoft Excel to work out the budget quicker, although it cannot present the literal data, as well as the numerated one. So my solution is to use Microsoft Excel for the ‘main job’, which is to work out the budget and then to transfer the data to Microsoft Word to produce the reports. I think this is the most efficient way of doing this project, because it will satisfy the needs of the potential users and I’ll prove it at the end. I chose Microsoft Excel because I believe tools such as macros, â€Å"what if† statements and pivot tables would ease the use of the system and will make it more understandable and user friendly. What are the user’s requirements? In order to consider the user’s requirements I did a questionnaire (see below): Questionnaire: 1.) What is wrong with the current system and why do you need a new computer-based system? 2.) What do you expect from the system? 3.) What IT skills do you think you have? (e.g. can you work with the operating system, do you know how to use Microsoft Office, etc.) 4.) What do you want the system to look like? I also asked the manager what her expectations were †¦ â€Å"As we are not familiar with ICT our main requirement is that the system should be user friendly and easy to follow. The only data that will have to be entered into the new system will be the assigned item number. When more than one of an item is required it will be entered twice, as this will be quicker. The rest of the information will be worked out by the system. Good luck!† Myra Ferreira Manager of Ki for Hair What do I expect from the system? The system must be easy to understand and use, so that any user with no computer knowledge could easily make use of the system. Much time will be saved as the computer will automatically set up the layout and the users will only have to input the required data. * First every user is going to have his/her own ID and password; * Once the user’s logged on, he/she is going to have access to the main directories, which are: the prices, the customer accounts and the monthly reports; * Every user will have the priority to edit information, excluding editing the prices; * The change (editing) of the prices can only be done by the manager; * The design of the system is going to match the colours of the salon. * To ease the use of the system I’ll use different tools such as macros (program that stores Microsoft Excel commands and eliminates the need of repeating series of calculations), pivot tables (allow you to easily sort and view data), â€Å"what if† statements (test cell contents and help you make decisions based upon them) and data filters (a method of sorting which hides information that does not match your criteria). * It must also be easy to update and edit, and most importantly easy to use. To make my project easier to read and understand, I’ll use different fonts and sizes as well as colours. In order to use the system as much as possible, the user’s system must include: Hardware requirements The hardware requirements must meet those set by Excel and Windows 95+ * IBM compatible PC * Pentium 100, K6-2 100 or above * 32Mb of RAM * 1GB Hard Drive space * Printer The above requirements or those required by both Excel and Windows 95 or above. The printer is required when a hard copy of the programs output is required. Software requirements * Windows 95/98/98SE/2000/XP * Microsoft Office (depends on the operating system, e.g. Microsoft Office 97/2000/XP) The system itself will be developed in MS Excel. Excel will also be required to run and use the system. The developer/user must have running a version of Microsoft Windows 95 or later. As Microsoft dominates the software market and MS-Excel will not run on other operating systems such as Linux, Unix, and Solaris etc. However in this case the system is aimed at the average user who will only be using a MS Windows environment. What skills and knowledge will be needed for the user to manage working with the system? * First, he/she will need to know how to work with the operating system * He/she should have basic knowledge of how to use Microsoft Office and particularly Microsoft Excel. * He/she should have basic thinking skills such as knowing how to learn and seeing things in the mind’s eye and personal qualities such as self-management and integrity To make my system work and be more efficient, I will: * Consider the user’s requirements very carefully, e.g. the layout, appearance, colour restrictions and the paper size, while I’m carrying out the design * Prepare a test strategy and test plan * Evaluate the final solution * Write user manuals on how to use the system I’d have created. Input, Process and Output Input-Process-Output. These are the basic functions of a computer. Data must be fed into the computer (input), which is then analysed and reorganised (process), and then it is displayed or printed (output). Input- it’s the data the user will be putting in, in my case the number of haircuts, blow-dries, etc. In order to make my system work more efficiently I’ll use data validation such as putting certain letters or numbers in certain cells. The process- it’s the processing of the initial data put by the user and done by the system. The output- this is the final result of the input and the process; in my case the output is going to be a hard copy of the monthly reports.

Association of Human papillomavirus and Breast Tumours The WritePass Journal

Association of Human papillomavirus and Breast Tumours Abstract: Association of Human papillomavirus and Breast Tumours Abstract:1.  Introduction:1.1.   Breast cancer:1.2.  Epidemiology:1.3 . Breast cancer Pathophysiology: 1.3.1  Ã‚  Aetiology:1.4.  Ã‚  Human papillomavirus and Cancer:1.4.1.   High risk and low risk HPV types:1.5.   Signs and Symptoms:1.4.   Different types of Breast cancers:1.4.   Diagnostic tests:1.5.   Aims and Objectives:2.  Methodology:2.1. Method and Materials:2.2. DNA purification method from tissue:3.  Ã‚  Result:3.1. DNA Extraction:3.2. PCR:4.  Health and Safety:5.   Ã‚  Ethical Issues:6.  Ã‚  Literature search:7.  Ã‚  Statistical analysis:8.  Ã‚  Treatment:8.1. Drugs:8.2. Trastuzumab: 9.  Cancer prevention:9.1. HPV Vaccines and Cervical Cancer:9.2. Breast Cancer Vaccine:10.  Discussion:References:Related Abstract: Cancer arises due to abnormal changes or mutations, in the genes responsible for regulating the growth of cells. Human papillomavirus (HPV) is considered the aetiological agent for many cancers including cervical cancer. HPV causes disruption and loss of some of the viral genes such as L1 and L2 genes and also increases the expression of the early genes. Several studies have addressed a relationship with HPV and breast cancer, as different HPVs have been identified. Most of the studies were successful in finding evidence in correlation of HPV 6, 11, 16 and 18 in invasive ductal breast carcinoma by using different techniques including DNA extraction and PCR, however other studies achieved low positivity or negative result. The aim of this study was to find out the association of HPV and Breast cancer. DNA was successfully extracted from archived breast tissue samples using DNA extraction method. This DNA sample could be amplified by using PCR to find HPV genome specifically targeting E1 gene. This is an ongoing work by the supervisors of the project to try and detect HPV genome in breast cancer, if successful a vaccine could be developed against various strains of HPVs worldwide and it could save many lives. Keywords:     Human papillomavirus, DNA Extraction, Breast cancer, Vaccine, PCR, 1.  Introduction: 1.1.   Breast cancer: Breast cancer is a malignant tumour that originates in the breast tissue, mainly from the inner lining of milk ducts or the lobules that supply milk to the ducts, cancers that initiates from ducts are called ductal carcinomas and those originating from lobules are called as lobular carcinomas. Cancer occurs due to abnormal changes or mutations, in the genes responsible for regulating the growth of cells (Sariego, 2010). The change in the genetic information causes a cell to no longer carry out its function properly (Almeida Barry, 2010). The following figures show the two types of cancers Benign and Malignant. (Almeida; Shela, 2010)   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Figure: 2 malignant tumours Figure 1 and 2: above shows benign vs. malignant cancers. (a) A benign tumour is a mass of cells that remains within the tissue in which it originally developed. (b) The invasion of cancer cells into surrounding tissues is the hallmark of a malignant tumour. Malignant cells may break free from the tumour and travel to other locations in the body through the process of metastasis (Almeida Barry, 2010). 1.2.  Epidemiology: Breast cancer is one of the main health problems worldwide (Bao, 2011) and which resulted http://en.wikipedia.org/wiki/Breast_cancer cite_note-WHO_WCR-2 458,503 deaths in 2008 worldwide out of which 13.7%   are of cancer deaths in women and it is about 100 times more common in women than in men (Veto, et al., 2009). The table below shows how females are susceptible to breast cancer at different ages for example there is 1 in 8 risk of developing breast cancer in females in the U.K in lifetime. Table 1: Shows estimated risk of developing breast cancer by age, females, UK, 2008 UK, 2008    Adopted from: www.cancerresearch.uk http://info.cancerresearchuk.org/cancerstats/types/breast/riskfactors/ Date accessed: 20/01/11 The table 2 below shows that more deaths happens in females due to breast cancer than males as it can be seen from the table only 69 males died in 2008 in compare to 12,047 females. Table 2: Shows the number of deaths and mortality rates in the UK in 2008. Adopted from: www.cancerresearch.uk http://info.cancerresearchuk.org/cancerstats/types/breast/mortality/#age Date accessed: 20/01/11 The figure below shows the incidence and mortality rates from female breast cancer in EU countries. As it can be seen from the table Belgium has the highest rates of incidence in female breast cancer. Figure 1 above is a graph of incidence and mortality rates in EU. Adopted from: www.cancerresearch.uk http://info.cancerresearchuk.org/cancerstats/types/breast/incidence/ Date accessed: 20/01/11 1.3 . Breast cancer Pathophysiology: 1.3.1  Ã‚  Aetiology: Some of the suspected aetiological factors which influence the cases of breast cancer are family history, obesity, age, oral contraceptives and alcohol. Family history: A woman who has a family member with breast cancer increases double the risk of getting breast cancer in compare to a woman with no family history (Lancet, 2001). Obesity: obesity increases the risk of postmenopausal breast cancer by up to 30%, since levels of hormones rises with excess body fat such as oestrogen and insulin these are the common features of cancers. Age: older women are at higher risk.   Particularly women aged 50-69 are most at risk, predominantly those with a late menopause. Oral contraceptives: increases the risk by approximately a quarter but since people who uses are commonly younger women, therefore the risk is fairly low. Alcohol: drinking alcohol as less as one alcoholic drink each day increases the risk of breast cancer by around 12%. (Cancer Research U.K, 2008) Some other factors include: Lesions to  DNA  such as genetic mutations. There is link between mutations that can lead to  breast cancer and  oestrogen  exposure, found out by carrying out experiments. Another factor is when a body fails to carry out immune surveillance; it is a theory in which the immune system gets rid of malignant cells throughout ones life. Other factor is inherited defects in  DNA  repair  genes, such as BRCA1, BRCA2 and TP53 (Adams, et al., 2011). Figure 2 above shows the percentage of different genes with associated risk. Figure adopted from: Wooster and Webber, (2003) Date accessed: 12/04/11 Moreover according to many authors there is a potential link between the HPV and breast cancer. 1.4.  Ã‚  Human papillomavirus and Cancer: HPV genome is normally found in the cytoplasm of infected tissues however, the DNA of HPV types that cause cancer are integrated into the host genome. HPV causes disruption and loss of some of the viral genes for example (L1 and L2 genes) and also increases the expression of the early genes (Wang, 2007; Mera, 1997). Oncoproteins E5 interacts with MHC I and prevents its transport to the cell surface   therefore infected cells escapes the immune system consequently allowing the virus to establish persistent infections and thus progressing to cancer. E6 targets p53 for degradation and therefore prevents apoptosis of abnormal cells, whereas E7 inactivates Rb (retinoblastoma) function, which results in abnormal cell proliferation and disturbs the normal cell cycle regulation (Wang, 2007; WHO, 2006; Mera, 1997). P53 and Rb are tumour suppressor genes which stop tumours from developing (Mera, 1997). Incorporation of virus into host cell increases and sustains the growth of both virus and the host cell, thus resulting in the alteration of infected host cells into malignant cells (Mera, 1997; Wang, 2007) and ultimately invasive cancer. Figure 3 above shows different genes in HPV. Adopted from: Symptoms of HPV 2010 symptomsofhpv.net/113/hpv-16/ Date accessed: 07/04/11 Table 9 below shows the function of different genes within the HPV virus: Gene/Region Function E1/E2 Code for proteins which control the function of E6 and E7 genes. E4 Function largely unknown but may control virus release from cell. E5 Codes for a hydrophobic protein which enhances immortalisation of the cell. E6 Codes for proteins which inhibit negative regulators of the cell cycle .E6 products inhibit p53 which is a transcription factor for apoptosis (programmed cell death). E7 Codes for products which  Ã‚   bind to the retinoblastoma tumour suppressor  Ã‚   proteins thereby permitting the cell to progress through the cell cycle in the absence  Ã‚  Ã‚   of normal mitogenic signals. L1/L2 Code for  structural proteins  and formation of complete virus particles. LCR Necessary for normal virus replication and control of gene expression. Adopted from: Eurocytology eurocytology.eu/static/eurocytology/eng/cervical/LP1ContentMcontA1.html Date accessed: 19/03/11 The HPV (human papillomavirus) is a member of the papillomaviridae family and has a double stranded circular DNA genome (Wang, 2007). These viruses are small in size with 8kbp-long DNA genome and have no envelope (WHO, 2006). HPV genome contains early (E) and the late genes (L) which codes for early proteins (E1-E7), late proteins (L1 and L2) and a non coding long control region (LCR) (WHO, 2006; Mera, 1997; Govan, 2008). 1.4.1.   High risk and low risk HPV types: There are more than one hundred different HPV types that have been discovered (WHO, 2006) and these are divided into high risk and low risk types. HPV 16, 18, 31 and 45 are some high risk HPV types associated with most of the cancer, while HPV 6 and 11 are low risk non-oncogenic HPV types (Brown, et al., 2005; Govan, 2008). Table3: the following table shows some high risk, low risk and potentially risk HPVs. Classification HPV types High-risk 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 Low-risk 82, 6, 11, 40, 42, 43, 44, 54, 61, 70 Potentially high –risk 26, 53 Source: Govan (2008) HPV 6 and 11 are linked with up to 90% genital warts (Von Krogh, 2011), nevertheless after the examination of 55 genital wart samples from Slovenia, using polymerase chain reaction (PCR), the authors concluded that HPV 6 and 11 genotypes were detected in 96.4% of genital warts patients (Potocnik, et al., 2007). 1.5.   Signs and Symptoms: Changes that could arise due to a breast cancer are: A change in the size or shape of a breast A lump or thickening in an area of the breast Dimpling of the skin A change in the shape of the nipple, particularly if it turns in, sinks into the breast or becomes irregular in shape A blood stained discharge from the nipple (Dixon, 2005; Breast cancer, 2008). Figure 3a: above shows the symptoms of breast cancer Source: Healthbase (2008) http://blog.healthbase.com/2008_09_01_archive.html Accessed date: 11/04/2011 Normal anatomy of the breast: Female breast anatomy The structure of female breast is mainly made up of fat and connective tissue, but also contains milk ducts, lymph nodes, blood vessels and structures known as lobes and lobules (Rosen, 2009). Figure 4 above shows normal anatomy of breast tissue. The above figure adopted from: Mayoclinic (2009) mayoclinic.com/health/breast-cancer-early-stage/BC00001 Date accessed: 8 April 2011. Lobules and ducts Every breast has 12 to 20 lobules that protrude from the nipple and holds small alveoli; the lobules are connected together by a network of thin ducts (Rosen, 2009). Figure 5 above shows different parts in the female breast The above figure adopted from: Mayoclinic (2009) mayoclinic.com/health/breast-cancer-early-stage/BC00001 Date accessed: 8 April 2011. Stromata Spaces around the lobules and ducts are filled with fatty tissue, ligaments and connective tissue (stromata). The size of the breast is determined by the amount of fat it contains, the breast tissue is also sensitive to cyclic changes in hormone levels (Rosen, 2009). Figure 6 above shows the position of stromata in female breast. The figure adopted from: Mayoclinic (2009). mayoclinic.com/health/breast-cancer-early-stage/BC00001 Date accessed: 8 April 2011. Muscles Breasts are muscle free tissues, muscles lie beneath the breasts separating them from the ribs (Rosen, 2009). The above figure adopted from: Mayoclinic (2009) mayoclinic.com/health/breast-cancer-early-stage/BC00001 Date accessed: 8 April 2011. Arteries and capillaries Blood supply all the essential nutrients and oxygen to the breast tissue through arteries, capillaries and small blood vessels (Rosen, 2009). Figure 8 above shows the position of capillaries and arteries in and around the breast. Figure adopted from: Mayoclinic, (2009) mayoclinic.com/health/breast-cancer-early-stage/BC00001 Date accessed: 8 April 2011. Lymph nodes and lymph ducts The lymphatic system contains blood vessels, lymph ducts and lymph nodes that helps fight infection, lymph nodes are present behind the breastbone, under the armpit and in other parts of the body engulfs harmful substances that are in the lymphatic system and safely get rid of them (Rosen, 2009; Mayoclinic, 2009). Figure 9 above shows the position of the lymph nodes and lymph ducts. The above figure adopted from: Mayoclinic, 2009 mayoclinic.com/health/breast-cancer-early-stage/BC00001 Date accessed: 8 April 2011. 1.4.   Different types of Breast cancers: There are different types of breast cancer for example ductal and lobular and it depends on the type of tissue that it is derived from. Table 3.1 below shows the list of different types of breast cancer: DCIS ductal carcinoma in situ LCIS lobular carcinoma in situ Invasive ductal breast cancer Invasive lobular breast cancer Inflammatory breast cancer Pagets disease Breast cancer in men The following figures show some of the main types of the cancer that begins in different areas of the breast for example the ducts, the lobules, or in some cases, the tissue in between. These figures also show the different types of breast cancer, including non-invasive, invasive, metastatic and recurrent breast cancers. a.   Ductal Carcinoma in situ (DCIS)   Range of Ductal Carcinoma in situ (DCIS) Figures: 10 and 11 above show normal breast with non–invasive ductal carcinoma in situ (DCIS) in an enlarged cross–section of the duct. Adopted from: Breast cancer (2008) breastcancer.org/symptoms/types/dcis/diagnosis.jsp Accessed date: 20/01/2011 Breast profile A B C D E F G Ducts Lobules Dilated section of duct to hold milk Nipple Fat Pectralis major muscle Chest wall/ rib cage Enlargement Ductal   cancer cells Normal lobular cells Basement membrane Lumen ( centre of duct) Table 4: shows the annotation of the above figures (Trentham-Dietz, et al., 2011) b.  Ã‚  Lobular Carcinoma in situ (LCIS Figure: 12 above shows normal breast with lobular carcinoma in situ (LCIS) in an enlarged cross–section of the lobule. Adopted from: Breast cancer (2008) breastcancer.org/symptoms/types/ilc/tests/diagnosing.jsp Accessed date: 20/01/2011 Table 5 shows the annotation of the figure 12. Breast profile A B C D E F G Ducts Lobules Dilated section of duct to hold milk Nipple Fat Pectralis major muscle Chest wall/ rib cage Enlargement Normal Ductal cells Lobular cancer cells Basement membrane (Trentham-Dietz et al., 2011) a.  Ã‚  Ã‚  Ã‚  Ã‚   Invasive Ductal Carcinoma (IDC) Figure 13 above shows normal breast with invasive ductal carcinoma (IDC) in an enlarged cross–section of the duct. Adopted from: Breast cancer (2008) breastcancer.org/symptoms/types/ilc/tests/diagnosing.jsp Accessed date: 20/01/2011 Breast profile A B C D E F G Ducts Lobules Dilated section of duct to hold milk Nipple Fat Pectralis major muscle Chest wall/ rib cage Enlargement Normal duct cells ductal cancer cells breaking through the basement membrane   Basement membrane Table 6 shows the annotation of the figure 13. (Trentham-Dietz, et al., 2011) c.  Invasive Lobular Carcinoma (ILC) The above figure 14 shows normal breast with invasive lobular carcinoma (ILC) in an enlarged cross–section of the lobule. Adopted from: Breast cancer (2008) breastcancer.org/symptoms/types/ilc/tests/diagnosing.jsp Accessed date: 20/01/2011 Table 7 shows the annotation of the figure 14. Breast profile A B C D E F G Ducts Lobules Dilated section of duct to hold milk Nipple Fat Pectralis major muscle Chest wall/ rib cage Enlargement Normal cells Lobular cancer cells breaking through   the basement membrane Basement membrane (Trentham-Dietz, et al., 2011) Following are some examples of non-invasive cell growths:       d.  Non-Invasive Cell Growth Subtypes Solid Figure: 15 shows A cancer cells B basement membrane Adopted from: Breast cancer (2008) Accessed date: 20/01/2011 e.   Ã‚  Non-Invasive Cell Growth Subtypes Cribriform Figure: 16 above shows (A) cancer cells (B) basement membrane (C) lumen (centre of duct) Adopted from: Breast cancer (2008) Accessed date: 20/01/2011      f.  Non-Invasive Cell Growth Subtypes Papillary Figure: 17 above shows (A) cancer cells (B) basement membrane (C) lumen (centre of duct) Adopted from: Breast cancer (2008) Accessed date: 20/01/2011 g.  Ã‚  Non-Invasive Cell Growth Subtypes Comedo Figure: 18 above shows (A) living cancer cells (B) dying cancer cells (C) cell debris (necrosis) Adopted from: Breast cancer (2008) Accessed date: 20/01/2011 h. Vascular and Lymphatic Invasion Figure: 20 above shows normal breast with cancer cells invading the lymph channels and blood vessels in the breast tissue Adopted from: Breast cancer (2008) Accessed date: 20/01/2011 Table 8 shows the annotation of the above figure Breast profile A B C D E F Blood vessels Lymphatic channels Enlargement Normal duct cells cancer cells Basement membrane Lymphatic channel Blood vessel Breast tissue    1.4.   Diagnostic tests: Diagnosis of the breast cancer incorporates x-rays and screening tests and following are some of the important diagnostic tests that can be carried out before and after symptoms of breast cancer. Tests: Mammogram: A mammogram is the main screening test for asymptomatic patients who are over the age of 40 as well as for symptomatic adult patients (Bao, 2011).This test has a high sensitivity and specificity (Banks, 2004). If a mammogram does not find out an abnormality in patients with a clinically detected breast mass, additional imaging ultrasound and/or MRI should be carried out for further evaluation (Bao, 2011). Outcome:  Ã‚   The results are indicative of malignancy include: an irregular speculated mass, clustered micro-calcifications, and linear branching calcifications (Banks, 2004; breast cancer, 2010). The above figure 21 shows how mammography is carried out. Figure 21 adopted from: Breast cancer (2010) breastcancer.org/symptoms/testing/types/mammograms/ Accessed date: 02/04/2011 Breast Ultrasound: Ultrasound sends high-frequency sound waves through the breast and changes them into images on a screen. The ultrasound technician places a sound-emitting probe on the breast to carry out the test and there is no radiation involved (Matsuzaki, et al., 2010). Outcome:   The results are indicative of malignancy include: a hypo echoic mass, an irregular mass with internal calcifications, and enlarged auxiliary lymph nodes (breast cancer 2010; Moss, 1999). The above figure 22 shows how ultrasound is carried out. adopted from: Breast cancer (2010) breastcancer.org/symptoms/testing/types/ultrasound.jsp Accessed date: 02/04/2011 Breast MRI: MRI uses magnets and radio to produce detailed cross sectional images of the inside of the body. MRI screens high-risk women (breast cancer, 2010). The Sensitivity is 88% to 91%. Specificity is about 67% (Bluemke, 2004). Outcome: The results are indicative of malignancy include: a heterogeneously enhancing area and significant architectural distortion (Bluemke, 2004). The above figure 23 shows how MRI is carried out. adopted from: Breast cancer (2010) breastcancer.org/symptoms/testing/types/mri/ Accessed date: 02/04/2011 Biopsy: There are different types of biopsy techniques and among these techniques Fine needle aspiration (FNA) is the least invasive procedure and has high sensitivity and specificity  (Dayal, et al., 2011).   FNA is good for quick diagnosis of malignancy. Nonetheless, core biopsy is generally favoured, as it effectively differentiates between pre-invasive and invasive disease and is less chance getting inadequate sampling (Dayal, et al., 2011).   Outcome: Invasive ductal carcinoma is responsible for almost 80% of all breast cancers, cords of tumour cells among associated glandular formation, which make varying degrees of fibrotic response. Whereas invasive lobular carcinoma, small tumour cells that invade past the basement membrane of the lobules and form an Indian file between collagen bundles, usually appears as well-differentiated tumour cells that display tubule formation (Dayal, et al., 2011). 1.5.   Aims and Objectives: The aim of this project was to evaluate the association of Human papillomavirus (HPV) and breast cancer, additionally to collect the studies that support the presence of HPV DNA in patients with breast lesions worldwide. The archived samples diagnosed with breast carcinoma, will be used to extract the DNA by DNA Extraction method which could be further used for amplifying this DNA using PCR to detect HPV genome. This will ascertain the role of this virus in the pathogenesis of breast cancer and will also help the scientist for further investigation of this virus on biology of cancer. The following is the methodology of my project as how I carried out the experiment and extracted the DNA. 2.  Methodology: The methodology incorporates materials and method, health and safety, ethical issues and statistical analysis. 2.1. Method and Materials: The following table 9 shows the materials that have been used to extract the DNA. Materials Measurements Universal tubes 20 ml, 5ml Epindorf tube 1.5 ml, 500ul Gilson pipetts 2x 5- 50ul, 2x 0.1 – 2.5 ul,2x 100 – 1000ul, 1x 20 – 200ul Dry heat block ( incubator) Vortex Waterbath ( 37c) Centrifuge and microfuge 70% of alcohol to avoid contamination and spray bottle Ice box 10. Thermometer( to measure the temperature) 11. Spectrophotometer( OD reader) 12. Pipett   tips 13. Tissue and Cell LysisSolution  Ã‚  Ã‚   600ul (60ml) 14. Proteinase K 4ul ( 200ul) 15. RNase A 2ul (400ul) 16. Protein Precipitation Reagent 300ul (60ml) 17. Isopropanol 1ml (2ml) 18. Ethanol 70% 19. TE Buffer 35ul (8ml) 2.2. DNA purification method from tissue: The following is the method used to extract the DNA from the archived sample of breast tissue. Lysis of Formalin-Fixed, Paraffin-Embedded (FFPE) Tissue   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   i.  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Placed 10-50 mg of 10- to 35- µm thick paraffin sections into an appropriate tube. If using a larger amount of tissue, adjust the reagent volumes accordingly.   Ã‚  Ã‚  Ã‚  Ã‚   ii.  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Diluted 4  µl of â€Å"Proteinase K† into 600  µl of â€Å"Tissue and Cell Lysis Solution† for each sample, and mixed.   Ã‚  Ã‚   iii.  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Added 600  µl of â€Å"Tissue and Cell Lysis Solution† containing the â€Å"Proteinase K† to the sample and mixed.   Ã‚  Ã‚   iv.  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Incubated at 65 °C for 30 minutes; followed by a brief (10 seconds) vortex mix.   Ã‚  Ã‚  Ã‚  Ã‚   v.  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Cooled the samples to 37 °C and added 2  µl of â€Å"RNase A† to the sample; mixed thoroughly.   Ã‚  Ã‚   vi.  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Incubated at 37 °C for 30 minutes.    vii.  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Placed the samples on ice for 3-5 minutes and then preceded with total DNA precipitation (below). Precipitation of Total DNA Added 300  µl of â€Å"MPC Protein Precipitation Reagent† to 600  µl of lysed sample and vortex vigorously for 10 seconds.   Ã‚  Ã‚   ix.  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Pellet the debris by centrifugation at 4 °C for 10 minutes at ≠¥10,000 x g in a microcentrifuge. If the resultant pellet was clear, small, of loose, added an additional 25  µl of â€Å"MPC Protein Precipitation Reagent†, mixed, and pellet the debris again.   Ã‚  Ã‚  Ã‚  Ã‚   x.  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Transferred the supernatant to a clean microcentrifuge tube and discarded the pellet.   Ã‚  Ã‚   xi.  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Added 500  µl of â€Å"isopropanol† to the recovered supernatant. Inverted the tube 30-40 times.    xii.  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Pellet the DNA by centrifugation at 4 °C for 10 minutes in a microcentrifuge. Carefully poured off the â€Å"isopropanol† without dislodging the DNA pellet. Rinsed twice with 70% â€Å"ethanol†, being careful to not dislodge the pellet. Centrifuged briefly if the pellet was dislodged. Removed all of the residual ethanol with a pipet.    xv.  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Resuspended the DNA in 35  µl of â€Å"TE Buffer†. Source: Epicentre Biotechnologies 3.  Ã‚  Result: DNA is extracted by a DNA histological processing using PCR and DNA extraction techniques. These are techniques used to extract, amplify and copy small segments of DNA. It is fast and inexpensive because significant amounts of a sample of DNA are necessary for molecular and genetic analyses (Mendizabal et al., 2008). 3.1. DNA Extraction: DNA was extracted by using DNA extraction protocol written in the method section. In the DNA extraction different solutions were used for example Proteinase K enzyme is used to digest protein and to remove protein contamination from DNA and to get to the pure DNA (Ebeling, et al., 1974). Also different machines incubators, vortex and centrifuge were used to break down cell walls. Following the DNA extraction PCR is used to amplify the DNA to find HPV genome. 3.2. PCR: Using the PCR to amplify a segment of DNA firstly the sample is heated so that the DNA denatures or divides into two pieces of single-stranded DNA. After that an enzyme called Taq polymerase synthesizes builds two new strands of DNA, using the original strands as templates. This process causes the duplication of the original DNA. Each of the molecules now carries one old and one new strand of DNA. After that each of these strands can be utilized to form two new copies, and the process continues in this manner. More than one billion exact copies of the original DNA segment is achieved by repeating the cycle of denaturing and synthesizing new DNA 35 or 40 times. This whole process of PCR is automated and can be done in just a few hours. A thermocycler machine directs this process and is programmed to change the temperature of the reaction every few minutes to cause DNA denaturing and synthesis. Source: Bruce Foukes lab Accessed date: 20/01/11. There are many different types of PCR for example conventional PCR assays using consensus primers and highly sensitive Real-Time PCR (Hedau, et al., 2011). Following are the result of the DNA extracted using a machine called nanoviewer.   Many concentration of the DNA extracted are within the good range which is 1.8 – 2.0. This indicates that the samples have not been contaminated with protein. The following table 10 shows the result of the DNA extracted: Breast Tissue sample number Concentration ng/ul Results 33 101.5 ng/ul A260/280 = 1.990 8 47.5 ng/ul A260/280 = 1.939 77 33 ng/ul A260/280 = 1.886 54 15.9 ng/ul A260/280 = 1.904 76 105.5 ng/ul A260/280 = 1.835 25 93.0 ng/ul A260/280 =   1.958 12 29.5 ng/ul A260/280 = 1.735 13 26.0 ng/ul A260/280 =   1.877 7 143.0 ng/ul A260/280 =   2.014 4.  Health and Safety: The health and safety procedures were followed according to the requirement of the laboratory for this project and a copy of COSSH assessment was given to the laboratory technical staff and to the project supervisor 5.   Ã‚  Ethical Issues: Approval of UK’S ethical committee regarding the usage of the breast tissue samples has already been granted to the project supervisor and hence there is no need of further ethical approval for this project. 6.  Ã‚  Literature search: To understand the scope of the HPV and breast cancer very well 15 abstracts have been submitted at the beginning to the project supervisor that were conducted by many journals and research papers. 7.  Ã‚  Statistical analysis: This project is a laboratory based and therefore does not require any statistical analysis to be carried out. 8.  Ã‚  Treatment: Breast cancer is treated with surgery, radiotherapy, chemotherapy and drugs. There are many drugs that are used to either treat or reduce the risk of breast cancer and following are some example of these drugs: 8.1. Drugs: Table11 below shows the list of drugs used for breast cancer treatment   Herceptin (chemical name: Trastuzumab ) Tamofen (chemical name: Tamoxifen) Arimidex (chemical name: anastrozole) Aromasin (chemical name: exemestane) Avastin (chemical name: bevacizumab) Carboplatin (brand name: Paraplatin) Cytoxan (chemical name: cyclophosphamide) Daunorubicin (brand names: Cerubidine, DaunoXome) Doxil (chemical name: doxorubicin) Ellence (chemical name: epirubicin) Thiotepa (brand name: Thioplex) Trelstar (chemical name: triptorelin) Tykerb (chemical name: lapatinib) Vincristine (brand names: Oncovin, Vincasar PES, Vincrex) Xeloda (chemical name: capecitabine) Some of the drugs that are used are explained below. Tamoxifen: is a drug that uses SERMs (selective oestrogen receptor modulator) that attaches to the oestrogen receptors in breast cells and blocks the effects of oestrogen (Lacroix, et al., 2010). Uses: to treat men and both pre-menopausal and post-menopausal women, typically is used to: shrink large, hormone-receptor-positive breast cancers before surgery reduce breast cancer risk in undiagnosed women at higher-than-average risk of developing breast cancer However Tamoxifen is very cost effective (Noah-Vanhoucke, et al., 2011) Side effects: irregular menstrual cycles vaginal discharge or bleeding depression endometrial cancer 8.2. Trastuzumab: is a drug that uses HER2 (human epidermal receptor 2) inhibitors that works against HER2-positive breast cancers by blocking the ability of the cancer cells to receive chemical signals that tell the cells to grow. Uses: treat metastatic, HER2-positive breast cancer (Barok, et al., 2011) shrink large, advanced-stage, HER2-positive cancers before surgery Side effects: diarrhea anemia abdominal pain 9.  Cancer prevention: 9.1. HPV Vaccines and Cervical Cancer: Cervical cancer and sexual behaviour of population are directly proportional to each other, recent study shows that in the U.K HPV prevalence and possession increased consistently with increasing numbers of lifetime sexual partners, regular partners, and new partners in the last 5 years (Almonte, 2011). The two prophylactic vaccines Cervarix and Gardasil consist of virus-like particles (VLPS), these are recombinant viral capsids made by expressing HPV 16 and 18 L1 proteins in insect cells through the baculovirous (cervarix) or HPV 6, 11, 16 and 18 L1 proteins in yeast cells (Gardasil) (Kahn 2005; Wang 2007; Kirnbauer et al., 1993). The virus-like particles (VLPS) contains no viral DNA and therefore would not in any case cause an infection or cervical cancer in recipients (Wang, 2007). Cervarix: GlaxoSmithKline (GSK) produces cervarix vaccine; it is a bivalent containing HPV 16 and 18 L1 virus-like particle vaccines that works against HPV 16 and 18 infections and cervical cancer (Bayas et al. 2008; Govan 2008). A phase II study illustrated that Cervarix was 91.6% efficacious against occasional infections and 100% effective against persistent infection (Harper et al. 2004). Cervarix is made up of an ASO4 adjuvant which contains aluminium hydroxide and 3-O-deacylated monophosporyl lipid (MPL), ASO4 helps improve the immune system (Bayas et al., 2008). Gardasil: Gardasil is developed by Merck and Co; it is a quadrivalent vaccine containing HPV 6, 11, 16 and 18 virus-like particles (Adams, et al., 2007; FDA, 2006). A phase II efficacy study of Gardasil results demonstrated that the vaccine has 90% efficacy in preventing incident HPV infection and cervaical cancer (Viller, et al., 2005). In June 2006 Gardasil was licensed by the FDA for use in young and adult females between the ages of 9 to 26 for the prevention of cervical cancer, genital warts and precancerous lesions (FDA, 2006), it was also approved in September 2008 for the prevention of vaginal and vulvar cancers caused by HPV 16 and 18 (FDA, 2008). Both of the above vaccines are given in a series of three 0.5ml immunisations over a time period of six months prior to a young person becomes sexually active (Long III, et al., 2007; WHO, 2007). Figure 24 shows how the HPV DNA is detected in cervical cancer. The above figure adopted from: Global Link (2008) Date accessed 07/04/11 9.2. Breast Cancer Vaccine: Vaccine has been developed firstly against cervical cancer and now the scientists are trying to develop a vaccine against breast cancer, however   scientists are trying to develop a vaccine which could be useful against all the different strains of HPV such as 16, 18, 33 worldwide (Armstrong, 2010). Prognosis: Table 14 shows the five year survival rates for colorectal and breast cancer. (Howlader, et al., 2011). There is only 23% survival rate for distant spread in breast cancer this shows that there is a need for more research to develop a vaccine against different strains of breast cancers and to treat these cancers affectively and avoid so many deaths. 10.  Discussion: Breast cancer is a malignant tumour that starts from cells of the breast. Cancer occurs due to mutations in the genes responsible for controlling the growth of cells thus cells are unable to function properly (Sariego, 2010). Human papillomavirus (HPV) is considered as an aetiological agent for many cancers such as cervical cancer, breast cancer etc. High risk HPV types causes cancer by integrating into the host genome and causes disruption and loss of some of the viral genes such as L1 and L2 genes and also increases the expression of the early genes (Wang, 2007; Mera, 1997). The aim of the research was to find out the association of HPV with breast cancer involving DNA extracted from archived breast tissue samples using DNA extraction method. This DNA sample could be amplified using PCR to find HPV genome specifically targeting E1 gene. This is conjunction with other studies in which samples were amplified using consensus primers CpI CpIIG and targeted the E1 gene in a region conserved for 99% of most common HPV subtypes (Mendizabal, et al., 2008). Given that the tissue samples were not fresh but were paraffin embedded which are not as good as fresh tissue samples because formalin fixation could denature the tissue during sectioning and also the DNA extracted from FFPE (formalin fixed paraffin embedded) tissues are usually at low concentration and disjointed (Shi, et   al., 2006). Additionally the experiment was carried out very successfully because most of the results that have been obtained were between the ranges of 1.8 to 2.0, which are regarded as pure DNA sample and therefore contains no protein contamination. A positive and negative control should be carried out while amplifying the DNA because a positive control makes sure the technique is working satisfactorily by using a reacting material relatively similar to the test material and negative control tests the specificity of the reaction and ensures there are no false positives (Mendizabal, et al., 2008). Although good results have been achieved however there were some variations in the purity of DNA extracted from the breast tissue samples and that depends on many different factors such as some tissue samples were darker in colour than normal which suggests the samples were not as fresh therefore it gave a lower result than the normal range of 1.8 to 2.0. Additionally the low results also depended on the way the whole experiment was carried out, there had been some mistakes in adding or mixing different solutions and mistakes were constantly recorded in the lab book therefore the same mistakes were not repeated again. Moreover many different techniques have been learnt from this project including the usage of centrifuge, vortex, incubator and nanoviewer. Carrying out this project has provided a full understanding on how to engage in the practical work which is beneficial in future laboratory projects, this is an ongoing work by the supervisors of the project to try and identify the association between the HPV and the breast cancer, if successful then a broader vaccine could be developed against all different strains of HPVs such as HPV16, 18 worldwide and   to cure not only breast cancer but also many different types of cancers such as, cervical cancer, head and neck Squamous cell carcinoma, genital warts etc. This will reduce the amount of vaccination given to each patient and also it will have tremendous effect on the quality of life and will solve many problems and save many lives. Furthermore many studies have been carried out to find out the presence of HPV in breast tissue. Some were successful by getting 86.21% positivity of HPV infection in breast cancer (de Villers et al., 2005) this was in conjunction with other studies that have been successful in obtaining high positive result (Hening, et al., 1999; Gumus, et al., 2006; Kan, et al., 2006, Li, et al., 2002). Additionally according to a largest investigation on breast carcinoma specifically analysing mammoplasty and fibroadenoma specimens as a control group the authors were able to detect HPV DNA in 24.5% of the breast carcinomas but were unable to detect any in benign breast specimens (Damin, et al., 2004). However other authors have either achieved low positivity (Kroupis, et al., 2006; Tsai, et al., 2005) or HPV was totally absent ( Lindel, et   al., 2007; Gopalkrishna, et al., 1996). Therefore there are two different views on the association of HPV with breast cancer as it has been indicated by the above studies, which is normal because scientists can have different opinions sometimes. 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