Animal Farm. Analysis

This summary is not available. Please click here to view the post.

Dodge Ram Quad Cab Advertisement :: Advertising Marketing

Smash Tough The creators of the Ram Quad Cab make the case that this truck is illustrative of the new Dodge. This truck is, as indicated by the creators, more agreeable and simpler to ride in than different trucks. Moreover, stacking and emptying individuals and payload is made simpler when utilizing their truck. The Dodge organization makes the case that their full-size pickup truck is among the best and backs this up with great proof in this commercial. At the point when Dodge says in their initial sentence that their organization is constantly open for new thoughts, they could be recommending that different organizations are not as ready to acknowledge change. They likewise suggest that they give individuals what they need and anticipate from a truck, bringing about the organization's prosperity. Inferring that their organization is unbelievable due to their notoriety for having incredible trucks, they show total trust in the way that their truck is better in its group. This Dodge Ram 4x4, as indicated by the commercial, is the principal broadened taxi pickup ever with four entryways, putting it among a tip top gathering of vehicles. Apparently the organization is so certain about its item that they even anticipate it will win a fourth J.D. Force and Associates in the forthcoming year. Notwithstanding the proof, Dodge even makes an intrigue to the normal man by saying that they make their truck roomier for the most part since they believe it's a darn smart thought, accepting that they are giving individuals what they have generally expected from them. They stress what a pleased organization they are a result of their numerous accomplishments and their commitment to the purchaser. The Dodge organization doesn't make their cases gently. They back up their announcements with solid help. One case of this is their statement that they have a large, much increasingly financial inside and a major, agreeable secondary lounge that help to isolate their truck from the opposition. Much additionally persuading is their true proof by J.D. Force and Associates, noted for their trustworthy investigation of vehicles and trucks, who positioned the Ram Quad Cab as the Most Appealing Full-Size Pickup for the third year straight. These realities, combined with an engaging and energetic image of the truck, attracts the peruser and makes him progressively keen on the item.

The Importance of Cash Flow Management - Free Essay Example

An understanding of effective cash flow statement and its further management is vital tool for the long term survival of an entity`s cash flows. It is also a key factor in planning and in the competent performance of all aspects of operations. The phrase revenue is sanity, profit is vanity but cash is king is an appropriate phenomenon that companies have to consider and embedded in their cash management strategy. It should be noted that profits are not an acceptable means of measuring and ensuring good cash flow, since it is not a major piece of cash flow management. Once cash inflows and outflows are received and money paid out are not effectively considered and monitored, corporations may possibly not be able to settle their employees and vendors on time. Hence, lack of good cash flow management could lead to companies inability to pay their bills as and when they fall due but yet these companies may have huge profits in their annual financial statements. 1.0 Background of the study Discounted cash flow analysis is widely used in investment finance,  real estate development, and corporate financial management. Indeed, a managers primary goal is to maximise the value of his or her firms stock. Value is based on the firms future cash flow. (F.Houston 2007 ,p.10). How does bank estimate that cash flow and how that cash flow will be used in future investment? The answers to both questions lie in a study of financial statement and risk related to transactions concerned with. Analysts describe the activities of a business in either operating or financial terms. Usually, to evaluate its operating profit, a business firm buys raw materials and combine them with actor as capital and labour to produce goods and services. Later on, the company will sell these goods or services to others at a higher price enough to yield return above the cost of the raw material, capital and labour used. In financial terms, the business obtains funds through creditors and owners, a nd spends them for raw material, labour and fixed assets. To see if a firms management has achieved its objectives, we must analyse the companys return and risk measures. Measuring returns consist of calculating profitability and risk measurement for the bank. 1.1 Overview of the company The creation of the UK largest retailer goes back to 1919, when John Edward (Jack) Cohen a retailers product line started selling surplus groceries from a stall in the East End of London. The name Tesco originated in 1924 when he bought a shipment of tea from a Mr T. E Stockwell, from whom the initials TES come from and CO from Jacks surname. In 1929 Mr Cohen opened a flagship Tesco store in Burnt Oak, North London and founded in 1939 Tesco stores limited. Today the company is a public limited and employs 470,000 people in more than 14 countries, and is the UK largest grocery retailer and the third worldwide. In the UK: Over the next decade following its creation, Tesco opened more than 100 small stores, mainly in the London area. The company expanded rapidly across the United Kingdom. Started with the acquisition of smaller grocery chains including the nineteen stores Burnards chain in 1955, and has now, 2362 stores ranging from superstores to express and petrol stations. Since the 1990s Tesco has developed an aggressive marketing campaign in an attempt to overtake Sainsburys and become the UKs leading retailer since 1995. In 1992, the company launched is slogan every little helps followed by the Tesco Value range in 1993 and the launch of his loyalty scheme, clubcard in 1995. Today Tesco is the first retailer in the UK with a groups sales of  £62,537 billion, a rise of 6.8% and  £3,412 billion group trading profit (12.3% growth) Abroad: The Company is now present in more than thirteen countries since 1995 when it first expanded to Tesco Hungary to, the USA in 2007. Strategy: The Companys strategy has been revised since 1997, the year Terry Leahy was named chief executive officer. Tesco has developed a growth strategy, the one that was ambitious in its design. In the coming years, the company directed its expansion efforts on its core U.K. business, retailing services, international operations, and non food business. Store types: Tesco has Ex tra, Superstore, Metro, Express, Tesco.com. Store offerings: Food retail, Non food retail, Petrol stations, Home living range. Tesco personal finance: life insurance, pet insurance, home insurance, travel insurance, motor insurance, saving account, personal loans, secure investment bonds, online mortgage finder The company aims: This dissertation was dedicated to the financial area, especially to financial management and risk involved. The proposed title of this dissertation is as follow: How important is for manager to have a good understanding of cash flow statement in a retailing industry. 1.2 Aims and objectives The aim of this research was to evaluate the overall performance of retailing sector a case study of Tesco Plc being chosen by taking into consideration its cash flows and risk involved. The researcher aims to understand the issues related to cash flow statement and relate it to risk involved and how to improve the management cash flow. Furthermore setting some aims and objectives are of a high importance as they outline some targets, tasks, guide and thus facilitate the research process. Objectives Identification of the key factors included in a cash flow statement Establishment of the straight relationship between the cash inflow and cash outflow Identification of the element that affect (risk) the successful cash flow The areas in need of cash flow What are the advantages of good knowledge of cash flow analysis Recommendation of new strategies and techniques to improve organizations overall cash flow performance Rationale of the Study The essence of commissioning this research was to establish the need for the company managers to have a good and a deeper understanding of the cash flow statement. After having considered the rate at which corporations are faced with liquidations as a result of going concern problems. The dependencies of profit/ income statement for financing decision making by most businesses over the years have result to these corporations failing to meet the expectations of their long term objectives. With this study the managers would realise the importance of the role the cash flow statement plays in the organisations cash flows management status. The other annual financial statements do not through more light on the financing needs/ requirement and management of the entities. However, the cash flow statement provides more and strong indicators that assist corporations to know the strength and weaknesses of their cash flow generation approaches. 1.4 Significance of the study Cash flows information of a company is very significant element in providing users of financial statements with a basis to measure the capability of the business to generate cash and cash equivalents and the desires of the business to make use of those cash flows. The financial decisions that users (both shareholders and stakeholders) make depends an appraisal of the strength of the business to generate cash and cash equivalents by having regard to the certainty and their ability to generate those cash (Ramachandran, 2007). The cash flow statement deals with the consideration of information concerning the historical changes in cash and cash equivalents of a company and categories cash flows in to certain groups. This research will no doubt be a significant tool in financing decisions for managers, shareholders and stakeholders at large. 1.5 The Research problem In recent years so many businesses have had to depend on excessive borrowings from the banks, credit agencies and other financial institutions. Cash flow shortages result to increase in costs, due to interest companies need to pay on borrowed loans, late-payment which may lead to fines, and subsequently the discounts that could be lost for paying bills lately. Lack of cash flow improvements can compound these unexpected costs and could result to difficulty in accessing credit and unfavourable payment terms on some types of purchases. Eventually, corporations that get better in the manner in which their receipts of cash and payment of cash are managed would be more flourishing than their counter-parts. 1.6 Research question After identifying the aims and objectives of this study, the research attempted to answer the following questions. What is cash flow concept? How is it used in an organisation? What is the impact of financial statements when valuing the cash flow statement? What are the review conceptual models and theoretical fragments related to cash flow? What review cash flow statement used by Tesco? What are the risks faced by the company when evaluating their cash inflow and cash outflow? The overall impact on cash flow statement inside and outside the industry 1.7 The dissertation outline The study has been organised in a manner that makes it much easier to read and understand. As a consequence the outline is as follows: Chapter one: introduction was concerned with general overviews of the study by presenting the aims and objectives, the significance of carrying such research as well as some questions faced by managers when valuing their liquidity. Chapter two: literature reviews was applied as others opinion, what authors has writing and thinking about cash flow management. Chapter three: methodology was highlighting the different techniques and approach used to carry out our research so that readers and manager can have a Chapter four: data analysis was presented as the methodology used to conduct this research successful .it furthermore presented the chosen analytical method in accordance with qualitative approach chosen in this study. The data collected are analysed using a qualitative analytical method the methodology used to conduct this study has been discussed. in this chapter and evaluated in accordance with the theoretical framework established from the literature review. Chapter five: conclusions and recommendations 1.8 summary This chapter gave an insight of the research project by presenting the company Tesco plc which is subject to inquiry, highlighting the aims and objectives, and discussing the significance of carrying such project as well as the limitations. The subsequent chapter reviews the literature of direct marketing, discussed by prominent authors.

Social Constructivism And Its Impact On Regular Basis

People are often known to be storytellers, narratives are told about individual stories and what such experiences depict. Societies and cultures, generally, possess an understanding of past and future views in regards to conflicts, peace building or reconciliation. Similarly, organisational understanding and intervening of the culture comes from a concept of stories assisting organisational development on regular basis (Boyce: 1996). This view takes social constructivism, critical theory and organisational symbolism into account. Such stories form basis of management practices with varied intricate issues, but these help functioning of the organisation regardless of the challenges. This pragmatic organisational behaviour is a perspective’s consequence, but an interesting concept for present managers (Griffin: 1993: 27-42). Individual consideration of all involves the view of idea development within the organisation, whilst taken altogether, a more focused evaluation is provided for storytelling concept in an organisation. Therefore, storytelling could be briefly explained as a means of social interaction for a direct outcome (Wallis: 1993). The article hence, focuses on the understanding of such learning facilitator tools for critical understanding of situations in an organisation, such as Univision, causing not only organisational misbehaviour but also mismanagement. Reflection of experiences form basis of exploring unexpected outcomes involving both feelings andShow MoreRelatedLev Vygotsky Essay1668 Words   |  7 PagesThe psychology theorists of the past have shaped the classrooms of the present. There are many theorists that have affected the teaching styles of today and a theorist that has had a major impact is Lev Vygotsky. Vygotsky’s work interests me much because his concepts and i deas encompass many of the ways in which teachers teach in today’s classrooms. The ideas he presented have contoured the strategies of teachers. It is interesting to look into the reasons why teachers have adopted some of theRead MoreResponsibilities of a School Teacher627 Words   |  3 PagesAnytime we as humans interact with one another we present a point of view. In learning theory, constructivism describes a way of knowledge in which we generate meaning by way of experience. This view holds that each student has a unique background, with unique needs, so becomes quite complex and multidimensional. Just as students have unique perspectives, so do teachers. We also know that how teachers view the world, how they think about problem solving, and what they choose to include and excludeRead More Effective Teaching Essay2056 Words   |  9 Pagesstudents can engage regardless of their backgrounds. Concerns specific to that lesson related to children not having regular acce ss to gardens and outdoor areas, a common concern with many high density suburbs and high-rise apartment blocks. The core of each activity is based around pedagogical questions to enable the entire class to participate, while still having a psycho-social element at the end, where students can add their personal experiences and relate the lessons back to their real lifeRead MoreAnalysis Of Eriksons Theory On Early Childhood Education1212 Words   |  5 PagesIntroduction Jean Piaget once asked, â€Å"Are we forming children who are only capable of learning what is already known?† With there being so many theoriest whose research and ideas have made an impact on early childhood education. Knowing the teoriests and the ideas that they had is vital in the education profession. Erik Erikson Hope is both the earliest and the most indispensable virtue inherent in the state of being alive. If life is to be sustained hope must remain, even where confidenceRead MoreThe Impact Of Training And Development On Organizational Effectiveness2072 Words   |  9 PagesThe Impact of Training and Development on Organizational Effectiveness Yvette Wilkinson Capella University 06/17/2016 Introduction: Overview Assessment of the Fundamental Competencies needed for the practice of Training and Development The fundamental competencies needed for the practice of Training and Development can be broken down into two separate areas that need to be assessed in order to understand the full impact of the two different areas. The areas ae foundational competenciesRead MoreDemonstrate Your Understanding Of The Teacher’S Role In1635 Words   |  7 PagesThe base of any nation and culture is established by preparing the human resource, mostly through formal methods of education, which eventually lends towards nation building. Due to its great ‘moral’ potential to impact an entire generation, formal education has always been valued by social institutions especially governments and civil societies. Thus, the role of a teacher came to be looked upon as a ‘noble’ one. In today’s changing global and local context, the role of a teacher poses unique challengesRead MoreThe Effects Of Media On The Media Influences Viewers1587 Words   |  7 Pagesfor entertainment or news is overly influential, persuasive, and authoritative. Through these characteristics, any type of information or message influences its massive audience. Because of this, what Americans see – or fail to see- has a powerful impact on how they view other races. Young children are especially vulnerable to the information they are exposed to. TV is a vehicle to provide experiences and information not otherwise available to them. Older audiences, however, are also vulnerable toRead MoreActor in International Politics2604 Words   |  11 Pages The problem of actors is one of the central, and at the same time one of the most controversial in the study of international politics and relations.  Indeed, one of the main criteria of international relations is the presence of re gular interactions between the social communities geographically separated by political boundaries.   In international relations, actors are those whose activity goes beyond one state and, therefore, participate in cross-border relations and communications.  InRead MoreThe On The Family System Of Cybernetics And The Influence Of Feedback2036 Words   |  9 Pageshighlighted in the case that include non-compliance to the medications prescribed to the patient, declining kidney functioning and cirrhosis of the liver, and challenges that are arising in taking care of the children from the social perspective. This report will carry out a social assessment of a patient suffering from these issues and will focus on providing a treatment plan and suggestions that can improve the present state of health of the patient. Cognitive Behavioral Therapy The techniques basedRead MoreConstruction of Positivity in the Indian Scenario3291 Words   |  14 Pagesperspective. The above study yielded a pleasantly surprising result—the common perception that we as a society are extremely negative and cynical in our attitude was found out to be completely untrue. Index Terms- Positivity, Positive Psychology, Social Constructionism, India I. INTRODUCTION Positivity refers to the degree to which something is positive or the quality or state of being positive. Positivity is that which accepts the world as it is, takes inspiration from it and sees the brighter

The Death Penalty Is Wrong - 847 Words

Many call the death penalty inhumane, and a large number of countries no longer execute criminals. However, the U.S. has kept capital punishment because it deters criminals from committing murders that place them in the position of the death penalty. However, the death penalty is wrong. No one deserves to have their life taken away by another human, even if they are guilty of murder. Death penalties are first recorded in the eighteenth century B.C.E. In the eleventh century C.E., William â€Å"the Conqueror† would only allow people to be hanged in cases of murder. In 1608, Captain George Kendall became the first recorded execution in the U.S. As the U.S. emerged as a sovereign nation, many questioned the use of the death penalty. By the nineteenth century, abolitionist believed that America had evolved morally and petitioned to have it repealed(DPIC). They had no success. Now, about 60 percent of the states in the U.S. have a death penalty, but some want it declared unconstitu tional. In court cases, though, the Supreme Court has upheld the death penalty as constitutional. The debate will continue. Morality is a big question when considering the death penalty. Ultimately, the moral question surrounding capital punishment in America has less to do with whether those convicted of violent crime deserve to die than with whether state and federal governments deserve to kill those whom it has imprisoned. The legacy of racial apartheid, racial bias, and ethnic discrimination isShow MoreRelatedThe Death Penalty Is Wrong1321 Words   |  6 PagesThe death penalty is a controversial issue in Texas. People support it because they are unaware of the unknown facts. People believe that the death penalty guarantees criminals being punished and justice being made. However, there are innocent people who have died because of the hateful vengeance by the prosecutor seeks. There are many reasons as to why the death penalty is wrong. There are many ways of killing the defend ant after they have been sentenced to the death penalty, some of these includeRead MoreThe Death Penalty Is Wrong !2056 Words   |  9 PagesThe Death Penalty is wrong!! Imagine Sierrah coming to court and hearing the judge say she is sentence to die. Imagine waking up every day in a cell waiting to die. There are no contact visits and she is in a cell 23 hours of the day by herself. She wait on death row for two decades until finally her day of execution comes. The guard comes up to cell twenty eight and says it’s time to go and takes her to the death house. She gets the last meal and says final goodbyes before being strapped to aRead MoreThe Death Penalty Is Wrong Essay1140 Words   |  5 PagesThe death penalty, properly known as capital punishment, has always been a controversial topic. People of the United States often find themselves in heated discussions over whether or not the death penalty is right. Some would argue the death penalty is right for a small percentage of certain crimes. Although the death penalty can be used as a tool of justice, I still think the death penalty is wrong because it goes against many American beliefs.   Ã‚  Ã‚   To begin with, the death penalty violates theRead MoreThe Death Penalty Is Wrong1495 Words   |  6 Pagesthe people s security, however in what manner can those same people make certain that these laws are doing what they are meant for? The death penalty is contended to be a just punishment equivalent to the wrongdoing committed, but is it truly, if it means lowering others to turn into that what they are against. â€Å"Always I have concluded the death penalty is wrong because it lowers us all; it is a surrender to the worst that is in us; it uses a power—the official power to kill by execution—that hasRead MoreEssay on The Death Penalty Is Wrong1073 Words   |  5 PagesThe death penalty is absolutely outrageous. There is no real reason that the government should feel that it has the right to execute people. Capital punishment is murder just as much as the people being executed murdered. The is no need for the death penalty and it needs to be abolish ed. It goes against the Constitution which states that there will be no cruel and unusual punishment. There is nothing crueler than killing a person. A perfect example of the death penalty going awry is the state ofRead MoreDeath Penalty: Killing Is Wrong1044 Words   |  5 PagesDeath Penalty 2 Death Penalty: Killing is Wrong To many of us death is a scary thing. We will all die one day, but when someone else takes another person’s life we think of that as wrong in many ways. Killing is wrong. If you take someone else’s life in the United States of America you go to jail. Of course you must be proven guilty of that murder before being charged. It doesn’t matter where you live in almost every state, city and town if you kill someone you are looked down upon andRead MoreThe Death Penalty Is Right Or Wrong981 Words   |  4 PagesMany people question whether the death penalty is right or wrong. Issues regarding the possibility of putting an innocent man to death based on faulty investigative work and a flawed legal system are often explored. References to the concept of lex talionis are made, wondering why rapists are not raped and sadists are not beaten in a legal system that kills killers. A killer takes another s life, liberty, or chance at happiness? Is it wrong to take the same fr om them? How can taking a life for aRead MoreThe Death Penalty Is Wrong And Inhumane Essay1170 Words   |  5 Pagesto death is difficult to completely comprehend. The physical procedure involved in the act of execution are easy to grasp, but the emotions involved in carrying out a death sentence on another person, regardless of how much they deserve it, is beyond comprehension. This act has been critiqued by many people from all around the world and it is our responsibility as a society to see that capital punishment is wrong and inhumane. Some oppositions to the death penalty include racial bias in death sentencingRead More The Death Penalty is Wrong Essay1057 Words   |  5 Pagesnbsp;nbsp;nbsp;nbsp;nbsp;The death penalty is absolutely outrageous. There is no real reason that the government should feel that it has the right to execute people. Capital punishment is murder just as much as the people being executed murdered. The is no need for the death penalty and it needs to be abolished. It goes against the Constitution which states that there will be no cruel and unusual punishment. There is nothing crueler than killing a person. nbsp;nbsp;nbsp;nbsp;nbsp;A perfect example of the death penaltyRead MoreDeath Penalty; Right or Wrong?2185 Words   |  9 PagesThe death penalty has been an issue that has continually caused tension in today’s society. The main discussion over this is whether or not the death penalty serves as a valid and justified form of punishment. We have reached the point where if the topic is brought up, extremists on both sides immediately begin to argue the matter. One side says increase in crime rate, the other says failure to discourage crime; one says failure to rehabilitate, the other says it saves lives; one says justice and

Raksha Bandhan free essay sample

Raksha Bandhan, (the bond of protection) or Rakhi, is a festival primarily observed in India, which celebrates the relationship between brothers and sisters. It is also called Rakhi Purnima in most of India. It is also celeberated in some parts of Pakistan. [3] The festival is observed by Hindus, Sikhs and some muslims. The central ceremony involves the tying of a rakhi (sacred thread) by a sister on her brothers wrist. This symbolizes the sisters love and prayers for her brothers well-being, and the brothers lifelong vow to protect her. The festival falls on the full moon day (Shravan Poornima) of the Shravan month of the Hindu lunisolar calendar. It grew in popularity after Rani Karnavati, the widowed queen of Chittor, sent a rakhi to the Mughal emperor Humayun when she required his help. [6] The festival is marked by the tying of a rakhi, or holy thread, which comes in many colors and designs, by the sister on the wrist of her brother. We will write a custom essay sample on Raksha Bandhan or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page The brother in return offers a gift to his sister and vows to look after her as she presents sweets to him. The brother usually presents his sister with an envelope filled with money however, other presents such as saris and clothing can be given. The brother and sister traditionally feed one another sweets. These sweets include anything from Jalebi, Kaju Katli, and Burfi. Since north Indian kinship practices give cousins a status similar to siblings, girls and women often tie the rakhi to their male cousins as well (referred to as cousin-brothers in regional parlance) in several communities. Unrelated boys and men who are considered to be brothers (munh-bola bhai or adopted brothers) can be tied rakhis, provided they commit to a lifelong obligation to provide protection to the woman or girl. [14] The chaste bond of love between a brother and a sister is one of the deepest and noblest of human emotions. Raksha Bandhan or Rakhi is a special occasion to celebrate this emotional bonding by tying a holy thread around the wrist. This thread, which pulsates with sisterly love and sublime sentiments, is rightly called the ‘Rakhi’. It means a bond of protection, and Raksha Bandhan signifies that the strong must protect the weak from all that’s evil. The ritual is observed on the full moon day of the Hindu month of Shravan, on which sisters tie the sacred Rakhi string on their brothers right wrists, and pray for their long life. Rakhis are ideally made of silk with gold and silver threads, beautifully crafted embroidered sequins, and studded with emi precious stones. It won’t be wrong to say the fashionable friendship band in vogue today is an extension of the Rakhi custom. When a girl feels a friend of the opposite sex has developed a kind of love too strong for her to reciprocate, she sends the guy a Rakhi and turns the relationship into a sisterly one. This is one way of saying, let’s just be friends, without hurting the other persons soft feelings for her.

The Art of Great Wall

The Great Wall of China, one of the world’s wonders and one of the greatest engineering projects in the history of the humankind is surrounded by myths and controversy which attract researchers and tourists all over the world. Preserved since ancient times, the Great Wall of China consists of scattered fragments which were built as the fortification lines but losing their defense value, are recognized as a historical and cultural relic.Advertising We will write a custom research paper sample on The Art of Great Wall specifically for you for only $16.05 $11/page Learn More Separate fragments of the Great Wall of China are more than 2, 000 years and the history of their creation is lost in centuries, giving rise to numerous myths and legends as well as debates of the historians. The construction of the first parts is dated back to the Warring States Period. The conventional view on the creation of the first fragments is that these fortifications lin es were the product of the struggle between Chinese farmers and nomadic horsemen at the end of the Warring States Period around 200 BC. However, there are scholars who oppose this traditional approach, viewing the history of this colossal project from a fresh perspective. For example, Nicola Di Cosmo considered the wish of Chinese governments to expand into the neighboring territories as the main precondition for intensifying the fortifications and building the walls. â€Å"Di Cosmo has pointed to an important shift in Chinese military strategy during the Warring States Period† (Slavicek, Mitchell, and Matray 20). Later, Quin Shi Huang who was the first emperor of the Quin Dynasty, managed to overcome his competitors and to unite China into a single empire. He is known for a number of political and economic reforms aimed at transforming the old China and strengthening the empire. Quin Shi Huang joined the parts of the Wall and extended it to a total length of 5, 000 kilometer s for the purpose of creating a formidable defense line in the north, destroying the old inner defensive systems such as the complexes of walls and watchtowers. â€Å"The giant wall would not only serve as protection against invading nomads but also stand as a symbol of the Chinese emperor’s great power† (Richardson 10). Only scattered parts of the original construction have survived till the modern times, and the precise length of Huang Di’s Wall is unknown. The majority of modern scholars believe that the Great Wall of that period was not less than 1, 500 miles as compared to 3, 889 miles of the present day construction (Slavicek, Mitchell, and Matray 26). That project of the Qin dynasty is defined as the First Great Wall, and the following projects of the Second Great Wall by Han Dynasty, the Third Great Wall by Jin Dynasty and the Final Great Wall by Ming Dynasty contributed to the original construction.Advertising Looking for research paper on art? Let 's see if we can help you! Get your first paper with 15% OFF Learn More At present, the Wall is not used as a defensive barrier. â€Å"The Great Wall completely lost its purpose, both as a military defense line and as a national boundary† (Slavicek, Mitchell, and Matray 4). The last battle took place at the wall in 1938 and since then it has been damaged by the sun and wind. Within the previous century, a significant part of the wall was robbed by the local inhabitants who used the rocks and stone for building their houses. The government used the materials of the Wall for more ambitious projects and ruined it for building the highways and enlarging the cities. It was only in 1984 that the President Deng Xiaoping started the restoration of the Wall, recognizing its cultural and symbolic value for China and its people (Evans 8). Initially built as a fortification line, the ancient Great Wall of China has lost its defense value and became a historical and cultural reli c of the country. The numerous myths surrounding the history of construction of the Great Wall are preconditioned with the remoteness of the date of its origin and the lack of knowledge of the Chinese citizens concerning the history and the purpose of creating the fortification line. As an important historical relic and cultural symbol, this colossal construction attracted attention of historians, archeologists and artists all over the world. The first well-known associated with the Wall says that one million of people were buried in the wall for making it stronger. â€Å"To date, however, no bones, human or otherwise, have ever been found in the wall, nor are there official records that humans, alive or dead, were deliberately or accidentally buried in the wall† (Evans 11). This myth was reflected in Chinese poems and fairy tales, but can be explained as the misinterpretation of the claim that millions of people died because they worked hard on the project of the Wall. Anoth er widely spread myth is that the mortar used in the Wall was made of crushed human bones. However, there is evidence that the Ming dynasty used rice as a bounding element for the wall and confiscated it from the south population for completing the project. The majority of these terrifying myths are rooted in the draconian methods of exploitation of the workers which were implemented by the Chinese emperors for completing the colossal building project. Like many other military constructions, the Great Wall of China was innovative for its time and required combination of innovative architectural designs and defense measures along with hard labor of millions of Chinese citizens, the whole garrisons of soldiers and prisoners. Though the Great Wall consists of scattered fragments built in different periods of time and projected by different people, the features of ancient Chinese architectural style can be found in it. There are five major types of construction and materials which were used in the construction of this ancient fortification line, namely stone, brick, rammed earth, adobe and cliff.Advertising We will write a custom research paper sample on The Art of Great Wall specifically for you for only $16.05 $11/page Learn More Rammed earth is the oldest type of construction which presupposed combination of wooden planks, clay and layers of earth. The samples of this construction can still be found in the present day Wall. Adobe walls were erected mostly in dry regions because the adobe bricks had to be dried in the sun after cementation. Though these walls could be easily eroded by rains, the accessibility and cheapness of the required materials were their advantages. Cliff walls construction means that the natural cliffs have been incorporated into the construction of the Great Wall. The stone walls have been popular among the Chinese builders for several millennia and were used mainly in the mountainous regions because of the a vailability of the necessary materials. The brick walls were used by the Ming dynasty and could be easily transported and modified. As a historical relic preserved since ancient times, the Great Wall of China can be regarded as storage of ancient Chinese culture and wisdom. The samples of rock art on the Wall are of great interest for historians and sociologists because they can tell much about the life of people and their system of beliefs. The architectural methods, military designs and constructions were really progressive for their time, making this project one of the recognized world’s wonders, a part of UNESCO’s cultural heritage and an important historical site. Disregarding all the myths and controversy surrounding the history of the construction of the Wall, its remains one of the greatest architectural projects in the history of the humankind and its art value is undeniable. The Chinese people are proud of the Great Wall and consider at least one visit to thi s important historical hub as their moral duty. As one of the colossal architectural projects, the construction of the Wall required sacrificing materials and human resources. Along with the lack of historical evidence from the times of its construction, the draconian methods used by the emperors for building the Great Wall of China give rise to numerous myths and scientific debates, however, not diminishing its historical and cultural value. Works Cited Evans, Thammy. Great Wall of China: Beijing and Northern China. Guilford: Globe Pequot Press. 2006. Print. Richardson, Adele. Great Wall of China. Mankato: Creative Education. 2006. Print.Advertising Looking for research paper on art? Let's see if we can help you! Get your first paper with 15% OFF Learn More Slavicek, Louise, George Mitchell, and James Matray. The Great Wall of China. Philadelphia: Chelsea House Publishers. 2005. Print. This research paper on The Art of Great Wall was written and submitted by user Jenny C. to help you with your own studies. You are free to use it for research and reference purposes in order to write your own paper; however, you must cite it accordingly. You can donate your paper here.

Marketing and HR Order ID.

Marketing and HR Order ID. Customer service is very important in any business as it determines the success of the business. It refers to the various services and support provided to the customers before they make a purchase decision, while they are buying products and after the purchase has been made (Zemke, 2006).Advertising We will write a custom essay sample on Marketing and HR Order ID. specifically for you for only $16.05 $11/page Learn More However, customer service recognizes that the two types of customers can be grouped into internal customers and external customers. Internal customers include the employees within the organization who can also buy the products while external customers are the outsiders who buy from the organization. In starting up a new coffee shop that is Wi-Fi accessible, it enables managers to transfer data from one location to the other branches. Given that there are 3 locations within a 50-mile radius, it may be difficult for the managers to travel from one point to the other in order to perform their activities. To do this effectively, the management model to be adopted for the coffee shop is the participative approach to decision making. The customers should be treated well in order for them to continue buying coffee from the shop. A participative management approach refers to the process of management that involves the employees to participate in the decision making process of the organization. It is the best approach to be used in this situation because customer service is more important to the business. The employees do not need to be left behind in the decisions made, because they are the ones who serve the customers and therefore can greatly contribute ideas in the decision making process. For example, they know the tastes and preferences of customers, the customer needs and some of the complaints made by customers on the products and services provided. The management may not have any idea on such crucial matters. The way em ployees are being treated will be reflected in the way they also serve the customers. The participative approach allows the employees to accept all decisions made by the management as they were involved in the making of the decisions. It is very rare to find any kind of resistance on decisions made. This enables them to be motivated in serving the customers (Maslow, 1954). Once the employees feel that they are valued as they participate in the decision making process, they also work hard to maintain their jobs and serve the customers in a good way. Empowerment enables the employees to make some necessary decisions by themselves in the various problems that customers may be facing. For example, a customer may request for a small discount and the employee can decide to offer the discount.Advertising Looking for essay on business economics? Let's see if we can help you! Get your first paper with 15% OFF Learn More Given the various locations of the business, th e management can allow the employees from the various locations to always communicate through the Wi-Fi before making any important decisions (Hamel, 2009). Once the management acknowledges their suggestions, it can use the Wi-Fi to inform them on what to do next. Every store requires about 10 employees. This may be very costly for the coffee shop if managers for every store were to be employed. Inputs and feedbacks can be provided over the Wi-Fi on any requirements for additions in the store as long as the Wi-Fi is accessible to all locations. The information exchanged can then be used to make decisions which should be communicated to the employees. However, the participative approach may not encourage some employees who may feel that their views have not been considered. For the coffee shop, a participative approach can reduce the controlling costs and also ensure excellent customers service, which is the main objective of the new business. References Hamel, G. (2009).The future o f management. Washington, DC: Harvard University Press. Maslow, A. (1954). Motivation and personality. New York, NY: Harper. Zemke, R. (2006). Best practices in customer service. New York, NY: Pearson.

A Critique Of Inside The Brain Essay

, Research Paper A review of the book: Inside The Brain The first thing that must be said for the book Inside The Brain, is that it made for really easy reading. Even though the book concerns itself with some subjects that, easy, can be confounding due to their proficient or medical nature, the text flows easy. The book was written to be read, non to be a mention or text edition. The content of this well written book was besides first rate. The beginnings quoted in the book were rather impressive, and the research that went into the undertaking was seemingly rather thorough as good. There is information contained in this book that should be had by all. If all prospective parents were to be given a transcript of this book, and if they were to really read it, the hereafter of our state, and our universe for that affair, would be a much brighter one. Some of the points made, including the demand for kids to be stimulated mentally get downing at an early age, are important. Armed with this information, any parent would be probably to pass more clip with their kids in an attempt to guarantee their ultimate success in life. It is a parent # 8217 ; s duty and duty to supply their kids with the strongest mental armament available in order to come in the rational battleground that will be their hereafter. Those who are non decently intellectually prepared for life will fall to the underside of the socioeconomic strata. They will populate a life of discord including deficient instruction, deficient wellness, substandard wealth, and substandard kids. This will perpetuate a rhythm of this type of individual from coevals to coevals. The writer of the book seems to concentrate on the immediateness of the job through the usage of some really startling statistics. His deduction is that if something is non done to do parents better at the ma nner they prepare their kids for the hereafter, we, as a society, will necessitate to be constructing many more prisons in order to manage the overpowering sum of social misfits that we will be bring forthing. The book does travel on to supply some hope for tomorrow every bit good as fright. The latter chapters focus more on the organic structure # 8217 ; s abilities to mend and mend the encephalon and head. Much attending is given to possible interventions and therapies for those enduring from enfeebling hurts and diseases. Along with explicating how the encephalon and associated tissue can mend themselves, many new avenues of intervention are discussed. Again these issues can be, due to their really proficient and scientific nature, really obfuscated with tech nical slang. Kotulak does an first-class occupation of avoiding these booby traps and delivers the intended information with every bit small immaterial proficient slang and academic prose as possible. He does non exclude necessary information, but instead he explains briefly and compactly what is being referenced. This once more makes the book educational piece at the same clip makes it an gratifying book to read. The lone defects that gave a sense of uncertainty to the content of the book can non be attributed to the writer but to some of his beginnings. Many of his beginnings, while being quoted, appeared to be back-pedaling from their finds. After any mentions to a specific racial group or ethnicity, in footings of correlational informations, were made, the quoted person seemed to add a statement intended to further a feeling of political rightness. This seems incorrect from a scientific position. When a scientist completes a survey, the informations can talk for itself. Equally long as the methods used for the survey are clearly outlined, the scientist should experience no duty to explicate the consequences of his survey in footings of political rightness. It is possible that these statements were made in order to forestall any feeling of animus from being directed toward the scientific community by any one ethnic or racial group. Other than this one spot of take awaying information, the book itself was great. Tax dollars would be good spent by supplying a transcript of this book to every citizen of the state. Baring that, it should be made standard issue to all parents taking their neonates place from the infirmary. A few hours spent reading this book, could assist parents raise a kid who could transcend all outlooks. The information contained in this book implies that a kid # 8217 ; s hereafter mentality is non predicated by his parents # 8217 ; familial make-up. A kid could excel the successes of his parents if his parents give him the right start in life. After all, is it non the dream of all parents to do their kid # 8217 ; s life better than their ain, in every bit many ways as possible. The book besides offers hope to the many victims of encephalon hurts and their households. Stoping short of denoting a remedy for these medical catastrophes, the writer offers hope in the signifier of many new discoveries in the countries of pharmacotherapies and encephalon imagination. The ultimate feeling that the writer of this book leaves his readers with is a sense of hopefulness, and if one accepts some of the premises of this book, everyone who reads it is, to some extent, better off merely for holding read it and holding exercised their head.

History of ECON 4 Essay Example | Topics and Well Written Essays - 500 words

History of ECON 4 - Essay Example Social wealth comes from the production of economic goods in a capitalist economy (Heilbroner, 168). Organization of economic activities leads to division of labor among individuals. The division of labor and the economic organization meets the material needs of the society, which creates social wealth. Max argues that production is done for producing exchange value, but the benefits do not last. Max argues that capitalist economies buy labor with money because production is an important part of the development. Labor power is a special kind of commodity because it involves the special kind of abilities of human beings. Labor is a special kind of commodity because individuals should be willing to sell their labor power. Max argues that individuals and employers should meet in the marketplace as equals. Employers should be able to put his employees in the position of a buyer’s disposal. It indicates that the laborer distances him or her from labor to be able to claim rights it rights. Labor is a special kind of commodity because individuals should not sell the labor he has created (Heilbroner, 169). The individual should sell the labor power because they do not own the means of production. Max argues that some people own the money while some individuals own labor power. It is the reason labor power is a special kind of commodity. Labor power exists in the capacity of a living person. According to Karl Max, interpretation of the increase in the population is in the context of a capitalistic fiscal system. He argues that a capitalist takes a huge role in the economic sense. He feels that offer capitalist labor relative trivial share of labor productivity. Capitalist introduce more machinery in the society to increase the value of surplus of labor efficiency. According to Max introduction of machinery, creates a surplus of individuals due to lack of jobs to create balance in the economy (Heilbroner, 170). The population is a result

Project Proposal ONLY Assignment Example | Topics and Well Written Essays - 250 words

Project Proposal ONLY - Assignment Example In the current decade, the company has been subjected to global financial risks, alterations in the leadership folio of the company as well as the changing demands and preferences of the customers worldwide. Maintaining balance between its quality management dimensions, its quantity dealings and environmental concerns were a major challenges to Ford’s leaders (Mourdoukoutas, 2015; Wolde, 2015). It was to survive these challenges that the company began inculcating computer information system in its automobiles, which were intended to help drivers to be in contact even when travelling, without compromising their safety needs. However, with a recent upsurge in the frequency of hacking and the number of hackers, many in the industry are forecasting privacy issues that might also affect Ford’s brand image (CNN, 2014). This validates the problem to range from the innovation sphere of the company to its sustainability management dimension, offering a wide scope of the research . As apparent from the stated facts regarding the computer information related problem faced by Ford in dealing with the current needs of the global world, the selected organization offers a wide scope of research. Expectedly, the research to be conducted with consideration to Ford shall help to understand the challenges that any other innovative companies may face to function profitably and sustain in the aggressively competitive market, especially when incorporating computing devices. This research will emphasize the effective integration of company reports published by Ford, within the recent years. News articles will also be used to obtain factual data of the subject matter. In addition, to guide the arguments with strong theoretical and tested methods, the research will also value case studies and past scholarly researches relevant to the problem

Iago’s Soliloquies and Intentions Essay -- William Shakespeare, Othell

Iago’s Soliloquies and Intentions In every play, there is at least one character that jumps off the page and begs for your attention. In The Tragedy of Othello the Moor of Venice by William Shakespeare, this character is Iago. Iago is a devious man, a liar, a manipulator, and a psychopath. It seems Shakespeare developed a very maniacal character but not one that is unreal. I feel as though we have our fair share of Iago’s in today’s society. Many politicians seem to fit into this category, manipulating people for manipulation sake. However, to me the most interesting psychopath of all, is in the play Othello. In this play, Iago is Othello’s trusted ensign. However, Iago is not what he portrays himself to be, to the characters in the play. In his soliloquies, he exclusively reveals to the audience his mal intent. He betrays Othello in the most deceitful ways, abusing Othello’s trust. Plotting against him, Iago seeks revenge on an unknowing Othello. One would conclude that Iago would have motive behind his ruthless and elaborate plans. However, it seems that Iago committed these amoral crimes, for power, for psychopathic reasons, and for sport. He has displayed his power over Othello by proving to himself, that he could in fact exploit those around him, distorting what they believe to be true. We will look into Iago’s soliloquies, dissect them, and discover his plans. Iago, the obvious villain in this love story gone array. Shows us his true colors from the beginning of the play. In act one scene one, Iago is speaking with Roderigo, he confides in Roderigo telling him â€Å"I know my price; I am worth no worse a place†. Here Iago is holding himself in high regard in an exceedingly conceited manner. He ... ...ful newly wed couple and destroyed them. In some respect, you have to admire how truly devious Iago is. He takes the innocent Desdemona and making her look so guilty when she did absolute nothing wrong. He successfully convinced Othello that Desdemona was unfaithful to him, so much so that Othello kills his innocent wife. Iago receives his title of lieutenant if only for a moment, and his revenge against Othello. Iago throughout the play uses his manipulation of words to destroy those around him. In the end, his plan was unveiled, however it was too late the deeds were done. Iago has the last laugh, his gift of language he keeps to himself "Demand me nothing. What you know, you know. From this time forth I never will speak word". He laughs knowing that he will never give the others the satisfaction of knowing why he did this. Evil is triumphant at the end of Othello.

A Taste of Honey How does Shelagh Delaney present the changing factors of Jo’s character? Essay

In this essay I am going to be looking at the play a taste of honey and looking at the factors of Jo’s character. This play was written in 1956 the writer Shelagh Delaney was only a teenager when she wrote this play Helen and Jo are mother and daughter and they live in tatty flats. Helen meets a man named peter and they get married. Helen leaves goes to live with peter. Jo meets a boy who is in the navy. They spend Christmas together Jo gets pregnant and the boy leaves. Jo meets another boy called Geof and they set up home together. Geof is bisexual. Helens marriage breaks up because peter goes off with a younger woman. Helen comes back to and moves back in and get rid of Geof and he leaves and then it is mother and daughter again In the play Jo is the main character as she is always present in the play. In the play Jo meets Jimmy who is the father of her child and she also meets Geof who is bisexual and they have a relationship, Jo also has relationships with her mother Helen. Jo and Helen doesn’t get on well with each other and Helen leaves Jo at home when she goes out in the play a lot happens too Jo her mother leaves she gets pregnant, she lives with a bisexual and her mother returns Thought out the play Jo’s character changes at the start Jo is critical as she says to her mother â€Å"your knocking them back worse than ever† she is capital and organised as she says â€Å"I hate to see an un-shaded electrical light bulb I will put my scarf around it†, â€Å"im not just talented im jeanious† When Jo meets peter her character changes she becomes as she says â€Å"she’s jealous† she says this because she is jealous of her mother. Jo becomes quarrelsome when she says â€Å"I can’t bear to see me being affectionate with anyone† Jo also becomes annoying. When her mother Helen leaves Jo becomes resentful of her mother as she says â€Å"you don’t half knock them back these days† this is her being resentful of her mother. Jo is also hurt as her mother has left her when she says â€Å"you like to leave me alone† she says this because she does not want here mother with her because she has hurt her. When her mother leaves she also feels unloved by her mother. Jo changes again when she meets Jimmy she becomes flirtatious when she says â€Å"I love you† and when Jo says â€Å"I can’t resist myself†. Jo also becomes coy when Jo says â€Å"it’s my school girl complexion† and â€Å"anything might happen† Jo also likes attention because she did not get any love of her mother. Jo also says to Jimmy â€Å"you enjoyed it as much as I did† she says this because she is getting the attention she wants. Jo character changes again when she meets Geof she becomes insulting my calling him â€Å"a big sister†. Jo also becomes cynical â€Å"it’ll always be number one by itself† and becomes frightened when she is heavily pregnant, she is frightened when she says â€Å"I don’t want this baby I don’t want to be a woman†. When Jo’s mother Helen comes back she gets rid of Geof this is when Jo is in labour and becomes less assertive when she says â€Å"are you coming back† Jo becomes resigned â€Å"by baby will be back† she becomes less assertive when she can’t argue back when she is in labour. Shelagh Delaney uses dramatic devices to show the changes into Jo’s character, the first one I am going to write about is Conflict and fights that take place between all characters; there are quarrels between Helen and Jo there is also quarrels and fights between Jo and Peter. When Jo physically attacks peter this is because he is taking her mother away from her. Helen and Jo have had another argument about Helens engament to peter. There is also conflict between Helen, Jo and Geof when they argue about the care of Jo. When Helen and peter are about to split up there is arguments’s between them. It is to avoid conflict that Geof leaves to avoid conflict as he is very selfless. In the play there is a lot of contrast there are love scenes juxtaposed with quarrels with Helen and Jo; Helen and peter and which Jo and Jimmy where they say â€Å"Will you marry me† and â€Å"I love you† and Helen shows love to Jo â€Å"why don’t you lie down† which is another love hate relationship In the play there are two very different people Jo is frightened, Critical, Determined and insecure; Helen is Selfish, bossy, neglectful, and disorganized. There are also 3 different men who visit the flat they are Peter who drinks, insults, and is homophobic; Geof who is bisexual, caring, supportive, and hard working; and finally there is Jimmy who loves, immature, persuasive, and reliable. In the play there is a use of music and dance, each character is introduced with some music can suggest aspects of there character the music gives a surreal effect and can help gives the time gaps in the play Use of dramatic unities is clear unity of place is shaven when everything in the play is in of near the flat people visit the flat, and leave. The only person who stays in the play the whole way thought is Jo. The unity of time is clear when in the play everything happens in a year Jo moves from a school girl to a working loving partner into a loving relationship to a parent. The unity of action is shown when the play comes full cycle. It is cyclical that Helen and Jo are alone in the flat and the cycle of deprivation continues but there is a new life on its way. Jo mirrors Helen in that they have both a failed relationship. In the play the use of language reveals the factors in which cause Jo to change; there are insults between the characters. There is also a use of expletives like â€Å"Silly Bitch† and â€Å"little bastard† and â€Å"sour faced old bitch†. The educated language of Helen shows her using impressive vocabulary like when she says â€Å"The only conclusion I can find in your immediate presents is your ultimate absents†. Jimmy also has an educated language as he has knowledge of Shakespeare. The social conclusions manifest aspects of Jo’s character. Poor housing is clear in Jo’s character; Jo lives in a small 1 bed-roomed flat and it has a shared bathroom with the other flat. The flat is in Manchester and it is by the ship cannel which is polluted; the flat is also by the gas works which smells, this means that the cost of housing in the area is low. Helen has a low income as she is a prostitute and Jo has 2 low paided jobs. Geof has a student grant from the government and he makes clothes for the baby as it is cheaper than buying them. Helen is a prostitute she properly became a prostitute because she might have had no money and she also had a child to support.

Drug Absorbed Administration - Free Essay Example

Sample details Pages: 11 Words: 3180 Downloads: 9 Date added: 2017/06/26 Category Medicine Essay Type Essay any type Did you like this example? Introduction The oral route is still the most desired route for the administration of medicinal products1 due to the ease and lack of inconvenience associated with this administration route, in comparison to others such as the pulmonary route or the more invasive intravenous route. The pharmaceutical industry has developed considerably over the past 40 years with respect to the rate at which new chemical entities are being discovered. This increased rate is primarily due to the invention of high throughput screening, but there is no correlation between the rate of synthesis of these novel compounds and the release of new drugs on the market due to the high failure rate during the development process1. In order to minimise cost and resources associated with this loss, effective screening methods for both pharmacological action and bioavailability have to be used. The most important process that influences bioavailability of the drug is absorption and the necessity of creating and us ing suitable models that can predict the in vivo absorption profile of a drug is absolutely critical in achieving the desired reduction in cost associated with the pharmaceutical development process. There are two primary phases of absorption for orally administered drugs; the first is dissolution of the drug in the aqueous media present at the site or sites of absorption1 the second is permeation of the drug particles in solution through predominantly the small intestinal membrane into the hepatic portal vein1. The main factors affecting dissolution of a drug in the gastrointestinal (GI) system are the pH of the environment, volume of dissolution media and the presence of food by either encouraging or delaying the passage of the dosage form into the small intestine where many drugs are absorbed. Permutation of the drug through the small intestinal membrane is influenced by several variables. The presence of influx and efflux pumps on the apical surface is a main cons ideration2. There are three main routes of absorption that drugs can take; transcellular absorption through the cells, paracellular absorption by passing thorough the tight junctions between cells or by using influx transporters present on the apical surface3. Efflux transporters are also present which act to eject the drug molecule out of the cell and limit bioavailability1. All of these processes and scenarios need to be considered in developing an in vitro model to accurately predict gastrointestinal drug absorption. The extent to which a particular model represents the results seen in vivo can be conveyed through a mathematical relationship known as the in vitro- in vivo correlation (IVIVC)2,4. The predictive power of this correlation ultimately depends upon the capacity of the in vitro method used to simulate and reflect what occurred in vivo. The fact that different models are able to do this to different degrees has been appreciated as different levels of IVIVC have been defined; levels A, B, C, multiple C and D with A being the highest level5. There are many factors to consider and appreciate when looking at IVIVC made from drugs absorbed from the gastrointestinal tract, as models are either based on the dissolution of the drug within the GI media at the absorption site or permeability of the drug across the intestinal membrane. This review primarily considers models used to simulate and predict drug permeability, with a discussion of the ability of each technique to reflect and predict the in vivo environment and response; which would allow a representative IVIVC to be formed. Don’t waste time! Our writers will create an original "Drug Absorbed Administration" essay for you Create order In silico permeability models These models are computer programs that aim to predict the absorption and permeability of a drug. One review6 gave a very good summary of the programming process and highlighted the specifications against which the physicochemical properties of drugs are judged. An advantage of using such a model is that a high turnover of compounds can be tested within a short period of time6, a property that makes it very practical in industry. But in terms of developing an IVIVC, this model has limited use7. One major argument against the use of this model highlighted by another review 1 is that absorption predictions are based only on the physicochemical properties of the drug. This assumption is false as there are other factors to consider such as drug à ¢Ã¢â€š ¬Ã¢â‚¬Å" membrane interactions through active transporters and efflux pumps1 Parallel Artificial membrane permeability assay (PAMPA) This technique is based on the formation of an artificial membrane by using a hydrophobic filter material as support upon which lecithin and organic solvents are placed upon to produce an artificial lipid1. One recent review8 greatly criticised the use of this technique in the drug discovery process. It was stated that there was no real benefit in using this technique over the cell culture methods such as caco-2 and MKCD cell lines because it was just as time consuming with less informative data being obtained8. One of the main advantages of using this technique was that it was less labour intensive and quicker to do9, but this was a main focus of the argument against use of the technique by this review. Due to the different manipulations such as testing in various pH that need to be carried out, the process was deemed just as labour intensive as the caco-2 or Ussing chamber method. An attempt to debate against the points raised by this review was done by another9 whi ch highlighted the ability to use this technique to obtain various information such as the partition coefficient and apparent permeability (Papp) of a drug. Nevertheless, both reviews failed to specifically highlight the strengths or weaknesses of the technique in creating IVIVC. It appeared that the capacity of this technique to do so is limited as there is a gross underestimation of active transport of hydrophilic compounds with low molecular weights 1. Ussing Chambers This cell technique involves the isolation of intestinal membrane and cutting the tissue into strips. These strips are clamped onto a suitable clamping device to produce a flat sheet between two chambers, the donor and receiver chamber1. The measurement is taken as the amount of drug that appears in the receiver chamber1. To monitor the viability of the intestinal tissue, electrical resistance is measured by placing a current across the membrane1. Only few studies have used this technique to reflect its capability but this has only been used to show a level D IVIVC, where drug candidates during the development process are placed in rank order. One such study10 presented this technique as being equally capable of ranking drug candidates when compared to caco-2 cells and the in situ technique of a perfused jejunum loop. One article11 opposes the use of this technique and presents the counter argument to the method being used to create such a correlation. The paper identif ied the ability of this model to be biologically representative but clearly stated that the technique is not robust enough to incorporate as a method which is routinely used in early development, due to the complexity associated with setting up the instrument. This is a good observation and highlights an impracticality of the method. Caco-2 cell lines and separated clones The method that has been supported in recent studies is the Caco-2-cell culture model that has been shown to effectively mimic intestinal absorption. These cells are human colon adenocarcinoma cells that undergo proliferation when in culture1 which are grown on small porous membranes that fit in the wells of welled plates. The sample of the drug being tested is placed on top of the membrane with the amount of drug that passes through being calculated and the Papp is determined. Arguments in favour of this method state that the ability of this model to reflect in vivo conditions is very good as not only can transcellular and paracellular diffusion occur, both influx and efflux transporters are present, allowing active transport processes to be considered1,12. Such transport systems are those for sugars, bile acids, the efflux transporter P-glycoprotein11 and the more recently discovered multiple drug resistance protein (MDRP)11. This view is supported by many whom consid er this model to be very representative of the prediction of intestinal absorption. A study by Yee13 analysed 36 drugs and observed the correlation between the apparent absorption (Papp) obtained from the cells and the percentage absorbed determined from in vivo testing. A correlation coefficient of 0.90 between percentage absorbed in vitro and in vivo was obtained, showing that the technique is capable of reliably predicting in vivo results13. Another study14 confirmed the predictive ability of this model using 20 compounds and also established a correlation coefficient of 0.92 between Papp and the percentage of dose absorbed To further support the use of caco-2 cells, some studies10,11 have highlighted the ability of this method to be used in early stages of development in order to produce level D IVIVC where drug candidates are placed in rank order. But despite all these positive aspects some13,15-16 remain critical of this technique because of an associated low lev el of reproducibility with gross variability in results from different labs15. This has been attribute to differing culture conditions within each lab13,16. For example one study highlighted the importance of culture nutrients and duration of cell feeding as more L-methyldopa was absorbed as the feeding time increased13. Another important limitation of the model that has been recognised is that as the number of cells within a cell line increases, the Trans epithelial electrical resistance (TEER), mannitol flux and cell growth changes1. The TEER is a validation tool used to quantitatively reflect the integrity of the monolayer as the viability of this cell culture diminishes17. The cell line is unable to express mucus17 which has been shown to act as a barrier to drug permutation in retarding drug contact with the apical membrane of the small intestine and a fixed pH is used in the model17. This is not reflective of in vivo as the mucus layer has been shown to retard per mutation and the pH of the small intestine changes. A strong counter argument against the use of caco-2 cells is that the predictive power of the method differs depending upon the main absorption route that the drug uses. Two studies14,15 have indicated variability in the Papp for mannitol, polyethylene glycol (PEG) 4000 and fluorescein that have low paracellular permeability in various batches of caco-2 cells from different origins. Another study17 clearly showed that caco-2 cells underestimated the absorption of amoxicillin à ¢Ã¢â€š ¬Ã¢â‚¬Å" a passively absorbed drug and was not able to truly model the absorption of drugs that are absorbed using a carrier-mediated process due to the saturation or under-expression of these influx carriers and the over-expression of the efflux transporter P-glycoprotein. This limitation of the caco-2 cell line is where the calu-2 cell line proves to be superior. This is a sub-clone of the caco-2 cell line that is isolated at a late pass age number and has been shown to express different levels of sucrase isomaltase and glucose transporters17. Arguments in favour of this model claim that it is more representative of the in vivo situation17 as it expresses levels of sucrase isomaltase similar to that seen in the human jejunum17. UDP-transglucoronyltransferase, an enzyme involved in conjugation metabolic reaction is also seen at a level that is more representative of that in vivo and also an IVIVC has been formed using the in-vitro data obtained from this model17. Another sub-clone of the caco-2 cell line is the HT29-18-C1. A study18 used this cell line and the information obtained was used to calculate a permeability coefficient (PC) for a particular compound. A relationship between the percentage absorbed and the PC was formed much in the same manner as that created using Papp and was shown to be a good model to use in the early development process. Although this method possesses a significant flaw whic h is that the tight junctions established in this cell line were not as tight as those seen in vivo 18, therefore allowing passive diffusion to occur to a greater extent than would normally occur. This was shown in the same study18 where the Pc of mannitol was ten times less than that seen in caco-2 cells, which is not reflective of in vivo conditions. Madlin Derby Canine Kidney (MDCK) cells The progressive changes in TEER seen in caco-2 cells have led to the use of Madlin Derby Canine Kidney (MDCK) cells as a model to predict intestinal absorption14. These are differentiated epithelial cells that form tight junctions when cultured in semi-permeable membranes14 that also possess transporters, but not as many as seen in the caco-2 cell line14. One study19 highlighted both opposing arguments and those in favour of the technique by comparing the ability of the model with not only in vivo data but also with the caco-2 cell line. The predictive power of the model was similar to that of the caco-2 cells for passively absorbed compounds that showed good permeability19. For those that were poorly permeable or were actively transported, the model was unable to accurately present the degree of absorption; for the latter this is due to the minimal transporters expressed by the MDCK cells19, resulting in a poor IVIVC 2/4/A1 cell line This cell line which originated from fetal rat intestine was reported to mimic the permeability of the small intestine to drugs absorbed via the paracellular route to a greater extent than the caco-2 cell line1. One paper20 clearly advocates the use of this cell line because of this point as the tight junctions seen are more representative with the extent of passive absorption being similar to that in vivo. In this study this cell line was transformed in order to improve viability and a sigmoid relationship between fraction of drug absorbed in vivo and permeability coefficient obtained in vitro was obtained. The predominant argument against the use of this model also presented by the same study20, was that the shape properties of the cell line were not similar to that of the small intestine. The cells are cuboidal as oppose to columnar and there was a lower number of villi present on the apical surface. This limits the models capability of reflecting transcellular or car rier mediated absorption, which are major routes for many drugs which negatively impacts the IVIVC created. Conclusion and the Future In examining the arguments for and against the different cell culture techniques, the caco-2 cell line appears to be the most reflective of in vivo absorption. This is because the cell line can express transporters, allow all routes of absorption, has an associated low operating cost, high reliability and throughput capacity. All these advantages make it a very practical and useful model to routinely use in industry. Nevertheless, there is still room for improvement as the in vivo environment is not completely shown with this cell line. One significant aspect omitted is the dissolution of the drug and the impact that this process has on amount of the dose of drug available for permutation. Therefore the next step in producing a completely reflective model that can be used to form a good IVIVC is the combination of methods to take into account the many aspects influencing bioavailability1 with an ultimate goal of creating an in vitro gastrointestinal system model. Incorp oration of a modified caco-2 cell line that has been co-cultured with other cells such as MDCK cells with an artificial digestive system model such as the TIM-1 model is an example of such steps that can be investigated into attaining the ultimate goal. Within the TIM-1 model there is still room for improvement but it does provide a foundation to build and develop upon. The incorporation of the newly created PBL dynamic gastric model to replace the gastric compartment of the TIM-1 would be a combination that would shed more insight into actual food effects on drug absorption and permutation. Developments similar to this would eventually lead to the creation of a very reliable and reflective in vitro model. Bibliography (1) Balimane PV, Chong S, Morrison RA. Current methodologies used for evaluation of intestinal permeability and absorption. J.Pharmacol.Toxicol.Methods 2000;44(1):301-312. (2) Emami J. In vitro In vivo relationships: Concepts, regulatory perspectives, advances and attempts. J.Pharm.Pharm.Sci. 2006 27 Feb;9(1):82-100. (3) Hu M, Borchardt RT. Mechanism of L-alpha-methyldopa transport through a monolayer of polarized human intestinal epithelial cells (Caco-2). Pharm.Res. 1990;7(12):1313-1319. (4) Emami J. In vitro-in vivo correlation: From theory to applications. J.Pharm.Pharm.Sci. 2006 16 Jun;9(2):31-51. (5) Yu LX, Amidon GL, Polli JE, Zhao H, Mehta MU, Conner DP, et al. Biopharmaceutics classification system: The scientific basis for biowaiver extensions. Pharm.Res. 2002;19(7):921-925. (6) Bergstrom CAS. In silico predictions of drug solubility and permeability: Two rate-limiting barriers to oral drug absorption. Basic Clin.Pharmacol.Toxicol. 2005 Mar;96(3):156-1 61. (7) Barr WH, Riegelman S. Intestinal drug absorption and metabolism. I. Comparison of methods and models to study physiological factors of in vitro and in vivo intestinal absorption. J.Pharm.Sci. 1970;59(Feb):154-163. (8) Galinis-Luciani D, Nguyen L, Yazdanian M. Is PAMPA a useful tool for discovery?. J.Pharm.Sci. 2007 Nov;96(11):2886-2892. (9) Avdeef A, Bendels S, Di L, Faller B, Kansy M, Sugano K, et al. PAMPA Critical factors for better predictions of absorption. J.Pharm.Sci. 2007 Nov;96(11):2893-2909. (10) Boisset M, Botham RP, Haegele KD, Lenfant B, Pachot JI. Absorption of angiotensin II antagonists in Ussing chambers, Caco-2, perfused jejunum loop and in vivo:: Importance of drug ionisation in the in vitro prediction of in vivo absorption. European Journal of Pharmaceutical Sciences, 2000 5;10(3):215-224. (11) Fearn RA, Hirst BH. Predicting oral drug absorption and hepatobiliary clearance: Human intestinal and hepatic in vitro cell models. Environ.Tox icol.Pharmacol. 2006 Feb;21(2 SPEC. ISS):168-178. (12) Stewart BH, Chan OH, Lu RH, Reyner EL, Schmid HL, Hamilton HW, et al. Comparison of Intestinal Permeabilities Determined in Multiple in Vitro and in Situ Models: Relationship to Absorption in Humans. Pharm.Res. 1995 May;12(5):693-699. (13) Yee S. In vitro permeability across Caco-2 cells (colonic) can predict in vivo (small intestinal) absorption in man Fact or myth. Pharm.Res. 1997;14(6):763-766. (14) Volpe DA. Variability in Caco-2 and MDCK cell-based intestinal permeability assays. J.Pharm.Sci. 2008 Feb;97(2):712-725. (15) Walter E, Kissel T. Heterogeneity in the human intestinal cell line Caco-2 leads to differences in transepithelial transport. Eur.J.Pharm.Sci. 1995;3(4):215-230. (16) Tsuji A, Takanaga H, Tamai I, Terasaki T. Transcellular transport of benzoic acid across Caco-2 cells by a pH-dependent and carrier-mediated transport mechanism. Pharm.Res. 1994;11(1):30-37. (17) Gres M, Julian B, Bourri e M, Meunier V, Roques C, Berger M, et al. Correlation Between Oral Drug Absorption in Humans, and Apparent Drug Permeability in TC-7 Cells, A Human Epithelial Intestinal Cell Line: Comparison with the Parental Caco-2 Cell Line. Pharm.Res. 1998 May;15(5):726-733. (18) Wils P, Warnery A, Phung-Ba V, Scherman D. Differentiated intestinal epithelial cell lines as in vitro models for predicting the intestinal absorption of drugs. Cell Biol.Toxicol. 1994 Dec;10(5-6):393-397. (19) Irvine JD, Takahashi L, Lockhart K, Cheong J, Tolan JW, Selick HE, et al. MDCK (Madin-Darby canine kidney) cells: A tool for membrane permeability screening. J.Pharm.Sci. 1999 Jan;88(1):28-33. (20) Tavelin S, Milovic V, Ocklind G, Olsson S, Artursson P. A conditionally immortalized epithelial cell line for studies of intestinal drug transport. J.Pharmacol.Exp.Ther. 1999 Sep;290(3):1212-1221.