Technology Review and Integration Plan Essay Example for Free

Technology Review and Integration Plan EssayIn the 80s children normally depended on flash card, heavy encyclopedia, libraries and their parents to learn. When the age of personal computers (PC) started to gain momentum in the 90s, children started to experience computer programs that help them learn. In the late 90s multimedia application distributed in Compact Disc (CD) can be installed into computer to provide an interactional learning for children. safe recently with the dramatic growth of the internet, nearly all children have access to an internet connected PC. This also boosts the demand for educational websites that provide learning tools each for a fee or completely free. There are probably millions of websites that can be classified as educational but only some studies that directs us which website are best for our teachers, parents and students. This paper examines educational websites for children by going through at least five educational websites. therefore fro m these five, detailed parity is done on three best educational website found. Technology Review and Integration Plan The internet which connects computers and servers around the world is now the leading antecedent of information.Vast amount of data can be gathered from internet. One of the very useful websites for teachers, parents and students are educational websites. They come either for free or for a certain fee. Free educational websites normally earn through advertisement. Five of the most notable childrens educational website are http//funschool. kaboose. com/, http//www. kidsknowit. com/, http//www. teach-nology. com/, http//www. kbears. com/, and http//nobelprize. org/. The best quality of the Knowledge Bears website is the futuristic submarine like vivid interface.This feature makes the site very attractive and easy to use. Although on the other side, since it is full of flash interactive animation, it loads relatively slower than a more text oriented website like the KidsKnowIt. com website. One of the most interesting features of the Funschool Kaboose Website is the kid oriented look of the graphical user interface like the one shown in Figure 2. This makes it easy for kids to understand the usage of the site. The negative side of this site is that it is more of games than information. Each join are consists of educational games.This makes it less informative than the two other educational websites. The KidsKnowit website contains a simple interface that allows it to be loaded quickly in every internet browser. It has more topics and more information than the Knowledge Bears and Funschool Kaboose website. Although it has some disadvantages compared to other sites, but overall, from cost, ease of use, availability, reliability and learning outcome this site proves to be better. however with the distracting Google ads, the KidsKnowIt website still gives the best experience.It would be easy to integrate these educational websites into the class room. First, time must be allotted in every subject to learn from these sites. Then initially, an overview should be given to all the children how to navigate through these websites educational tools. Then some rules must be set as to how long, what areas and what objectives must be met every time the students visit this site. Finally, an evaluation procedure such as how fast they accomplish the games or an exam about the subject matter must be provided to check the progress of learning.With all of these put in place, then there is no doubt that these sites will be very helpful in teaching students.ReferencesAbout us Kidsknowit Network Outreach Program. Retrieved August 15, 2008, from Kidsknowit Web site http//www. kidsknowit. com/about. php About us Kbears. com . Retrieved August 16, 2008, from Knowledge Bears Website http//www. kbears. com/about. html Main Page Kidsknowit. com. THE alone FREE CHILDRENS LEARNING NETWORK. Retrieved August 16, 2008, from KidsKnowIt Website http//ww w. kidsknowit. com/

A Process Oriented Approach to Waiting Line Management in a Large Pilgrimage Center in India Essay Example for Free

A Process Oriented Approach to Waiting Line Management in a Large Pilgrimage Center in India adjudicateThis article documents an innovative approach to eff delay line in the largest pilgrimage center in the world. By a judicious combination of mental process orientation and advances in Information Technology, the pilgrimage centers management has been able to dramatically change the pilgrims waiting experience.The pilgrimage location under study is Tirumala dictated in Andhra Pradesh state in India. The number of avengeors to this important location has been steadily increasing oer date. As of 2011, the location attracted approximately 30 to 40 trillion visitors a year. The primary objective of a pilgrim visiting Tirumala is to have darshan of the principle deity in the temple. The secondary objectives include tonsure (shaving head as a hybridizing of respect), offering donations, prasadam collection, thulabaram, arjitha seva (paid serve ups), local rubber-necking and shopping.The immense popularity of the temple and its location poses significant challenges to the management of the system. This temple is a tradition bound Institution. Therefore, some alternatives to resolve pilgrim waiting time are feasible and some are not. There are some hard constraints which may not stand the test of logic.The ability to manage the traffic volume is a function of processing rate (darshan duration) at the temple and darshan time available per day.This case study is an example of improving available effectiveness by using formal management methods in addressing an important real life problem in an under researched area.This pilgrimage center is located in the extension of Western Ghats and is popularly known as Tirumala. It is considered to be the abode of Lord Vishnu in the form of Venkateswara. The temple is the richest pilgrimage center, after the Sree Padmanabhaswamy tabernacle in Thiruvananthapuram, Kerala, of any faith (at more than 50,000 crore) and th e most-visited lay out of worship in the world. This center attracts a large number of visitors from all over the country no matter of their caste, religion, belief, social status and professional affiliation. The temple is visited by about 50,000 to 100,000 pilgrims daily (30 to 40 million people annually on average), darn on supererogatory occasions and festivals, like the annual Brahmotsavam, the number of pilgrims shoots up to 500,000, making it the most-visited holy place in the world.The temple is on Venkatadri ( excessively known as Venkatachala or Venkata Hill), the one-seventh peak, and is also known as the Temple of Seven Hills. Venkatadri, the hillock residing place of Lord Venkateswara is probably one of the oldest spectral institutions in India. It is known to exist for over a period of 2000 years. It has a recorded history of thousand years. Based on the recorded history, the rituals and daily routines in this sacred temple are universe performed without a break f or more than 1000 years.Over a period of time Venkatadri has evolved as an epicenter of Vaishnavism. Several prominent Hindu religious institutions both have established a presence in Venkatadri or have made this as place of their administrative headquarters. Today, Venkatadri is not only a religious institution, but it has also evolved as a social institution. It supports financially a group of thirty (higher) educational institutions. Its mission is to systematically promote the study of Vedas and Sanskrit literature. The temple also provides generous financial support for construction of similar temples (Venkateswara) elsewhere in the country.Over a period of 50 years, the number of visitors to the temple and the township has increased by eight fold. I960(2 million), 1970(4 million), 1980(7 million), 1990(11 million), 2000(16 million), 2010(30 million).Such a huge traffic generates tremendous stress on the social and physical infrastructure of the temple slew (Tirumala and Tir upati). Being a tradition bound organization, certain modifications (on procedure, layout etc.) are not acceptable. The devotees (exposed to agencyrn social norms) who come to the temple expect a better service quality and shorter waiting time. Thus, the managerial challenge is to balance the tradition, operational efficiency and increasing pilgrim expectations.Activities in the temple and the town and their management need to be also seen from a religious perspective. There is a divine dispensation in the institution, which may not be tinkered with in whatever modification(s) that are made in the facilities plan and management of activities.MethodologyThe product and its deliveryPilgrims from all over the country arrive in the temple town. Usually they reach the foothill which is known as Tirupati. The mode of transport is rail, road (public or private transport) and air. Having reached Tirupati, those who have their own transport directly proceed to Tirumala. Some spend a few ho urs in sightseeing and visiting other temples and religious locations in and a set on Tirupati.The distance between Tirupati and Tirumala is 19Kms. Andhra Pradesh State Road Transport Corporation (APSRTC) operates regular services between Tirumala and Tirupati. The round trip is about 2.5 hours including waiting time at both the boarding points.Having reached Tirumala, the pilgrims look for a suitable accommodation. There are about 5000 cottages owned and managed by TTD for pilgrims convenience. After (a brief) resting, pilgrims go for tonsure (there are 500 barbers who operate on a 3 shift basis 15,000 tonsures are done in a day). The annual revenue from export of hair (from tonsure) is Rs. 100 million. Following tonsure pilgrims go for a wash and bath in the holy tank in the middle of the temple town and then join the queue for darshan. Some pilgrims on arrival at Tirumala directly join the darshan queue and after the darshan visit the tonsure centre, take a bath in the holy tank and departure to their place of residence.There are 32 waiting compartments to house pilgrims while they await darshan. The average capacity of these compartments is 500. About 17,000 pilgrims can be held in waiting at any time. The average waiting time for darshan can turn between 2-12 hours depending on the day and season. There is tremendous uncertainty as when darshan would happen. There is also anxiety as how long is the wait. There is no (accurate) randomness to the pilgrims on what is ahead. Because of the commitment to the pilgrimage process, individual pilgrims go through this tedious experience with reverence and patience.Finally on a FIFO basis, pilgrims arrive in front of the deity. The actual darshan lasts for about 1.5 to 2 seconds. However, the pilgrims can have a view of the deity from a distance of 30 meters from the main entrance. The travel time is about 45 seconds. Actually, the passage towards darshan admits a file of 6 or 7 columns of pilgrims to go through t he darshan process simultaneously.After the darshan the pilgrims donate money at the Hundi, equivalent of donation box, located inside as well as outside the temple and then leave the temple premises. The Hundi collection is about Rs. 2000 million a year. Often, they stand in another queue to receive on the loose(p) laddu (there are several counters that sell laddu). Approximately, 75,000 laddus are sold in a day. In view of demand and supply gap, there is rationing and restrictions on how many laddus a pilgrim can buy.Tirumala Tirupati Devasthanam (TTD) the administrative agency in charge of this temple provides free meal to about 25,000 persons in a day. After receipt of laddu(s) and a meal, the pilgrim returns to his cottage or wait for a transport to go Tirupati and subsequently to his place of residence.

The Clothes Make the Man Essay Example for Free

The Clothes Make the Man EssayThe Grangerford family serves as an bothegory meant to show S protrudehern readers both the horror and the futility of execration and violence. TSIn the Grangerford home, the feud with the Shepherdsons is kept alive by the authority of Colonel Grangerford. As the father of a typically male-dominated Southern family, he sets the moral compass for them. CDHuck tells the reader that either day of the colonels life he put on a clean shirt and a full suit from head to foot made out of linen so white it hurt your eyes to look at it. CMColonel Grangerfords clean shirt projects the idea that he is a person of the highest moral quality, raze though he advocates racism, vengeance, violence and ignorance under his own roof. Huck voices the collective opinion of Southern society when he decides that the Colonel was a gentleman all over (p. 140) based almost entirely on the mans possessions. CSTwain uses the Colonel to show that white Southerners judge the mo ral quality of a man by his superficial appearance rather than focusing on his character.TSThe oldest two sons, Bob and Tom Grangerford, symbolize the pattern by which the family ideology is passed from generation to generation. CDBoth are draw as dressed in white linen from head to foot, like the old gentleman. (p. 141) CMThe Colonel imprints them with his belief system from the outside in. It is his rules and his understanding of the world that dresses the ideas of his children. CSJust as the boys reach to emulate their fathers external appearance, they also adopt his worldview and moral guidelines.TS gimps throttle moral and academic education is highlighted frequently during Hucks succession with him. CM Buck desperately wants to murder Shephersons, even though he doesnt know the reasons behind his familys feud. What makes the situation sadder is that he seems to compliments his enemies courage and unity, two of his familys core virtues, and defends them to Huck. CDThere a int a coward amongst them Shepherdsons, Buck says, not a one. (p. 145) His fathers corrupt teaching has go away Buck unable to recognize when he is acting immorally.When Buck fails to correctly spell the name George Jackson, he also demonstrates his academic shortcomings. CSTwain does this to show that even though Colonel Grangerford has enough money to educate Buck, he shields his son from the classroom to maintain control over what he learns. As a result of his limited education, Buck grows up as an incomplete man. When Huck first sees Buck, he notices that he hadnt on anything but a shirt, and he was very frowzy-headed.Bucks unfinished outfit symbolizes his deficient schooling, and the frowziness of his hair represents his fathers negligence in his moral instruction. Huck tells us that when he goes to Bucks room, Buck got me a coarse shirt and a roundabout and pants of his. (p. 131) The rough texture of the shirt is another metaphor for Bucks stunted mental growth, and its pi ssed construction reminds us of the stern control that the Colonel, who bought the shirt, exerts over his son.Twain suggests that the Grangerfords demise is directly related to their lack of education, when their inability to foresee the Shepherdsons ambush results in Bucks death. He shows the reader how the family stunted their intellectual and spiritual growth by focusing their time and energy on hatred, racism and cruelty. Any southerners of the time who shared similar values as the Grangerfords were likely given much to think about when they read this familys story and the price they paid for their hunched moral values.

Why Nestle Is Multinational Corporate Marketing Essay

Why cling to Is Multinational Corporate Marketing EssayIntroduction to MNC (Multinational Corporate)MNC (Multinational corporate) cognize started from 17th century which traces radical from Dutch East India Company. And this corporate structure much widely functioned in 21th century.According to Stuart Wall, Sonal Minocha and Bronwen Rees (2010), MNC (Multinational corporate) is a confederacy that has headquarters in one rural ara exactly has operations in otherwise country. MNC had defined by Dunning (1993) MNC be engages in FDI (Foreign Direct Investment) and owns or controls value-adding activities in more than one country. Typically the multinational would not just own value-adding activities, but might buy resources and create goods or services in a variety of countries. Multinational Corporate in 2007 an estimated 79000 multinational corporate, collectively controlled a total of near 800000 foreign affiliates, employed almost 82million people cosmoswide and accounte d for sales revenue of over $31 trillion, some 11% of world GDP. . (Stuart WallSonalMinocha and Bronwen Rees. 2010. pg. 31).Foreign Direct Investment (FDI) is any forms that investor earns interest in corporation which functions outside of the domestic territory of investor. withal that, foreign turn to investment needs a relationship between a parent company and it foreign subsidiary. It is also gives rise for multinational corporate based on their report Economy Watch (2010).What is Globalization?Globalization take to bes businesses transaction around the world.Research (Global Education, 2009) has shown that globalization have many meanings and definitions, but mostly known as the greater movement of people, goods, capital and ideas affected by the increments of the economic integration which in turn is propelled by the increasing trades and investments. It is like moving towards vivacious in a b exhibitionless world. There has always been a sharing of goods, services, knowl edge and cultures between people and countries. In recent years, the improvement of technologies and a reduction of barriers mean the speed of transfer is much faster. Globalization provides lots of variant types of opportunities and challenges (Global Education, 2009).Why draw near is Multinational Corporate? draw near is a multinational corporate since the headquarter is determined in Switzerland but operates businesses in the many other countries over the world such as Europe, United State, China, Malaysia, Hong Kong etc. As we know, snuggle is an infants product. Besides producing infants, Nestle has also produces some other products such as cocoa, yogurt drink, cornflakes, ice-cream etc which disregard easily found in supermarkets all over the world.Introduction to NestleIn 1860s, a pharmacist named Henri Nestle had succeeded developed a victuals for babies whom are unable to breastfeed. And his first success was to be able to feed a unseasonable infant who could not to lerate his mothers milk or any of the usual substitutes. (Nestle, 2010)In 1867, he adopted his own coat of arms as a trademark in 1867. In German Nestle means little nest. The Nestle symbol is universally understood to carry the meaning of nurturing and caring, security, nourishment and family bonding. These attributes are gloss over the guiding legacy for the company Henri Nestl founded which fulfills the commitment to Good Food, Good Life.The Nestl Coat-of-ArmsSources Nestle Sdn Bhd 2010In 1905 Nestl work together with the Anglo-Swiss Condensed Milk Company, the year after Nestl added chocolate to its line of foods. The newly formed Nestl and Anglo-Swiss Milk Company had factories in the Spain, Germany, United States and Britain. Soon, the company had full-scale manufacturing in Australia with wareho intakes in Hong Kong, Singapore and Bombay. Most production still took place in Europe. (English Tea Store, 2004-2009)At first, Nestle business was mainly based on milk and dietetic foods for children. Then, Nestl grew and diversified its range of products, through acquisitions and mergers with the already famous brands of that time. For example, the manufacturing of LACTOGEN began in 1921, and in the same year, a beverage containing wheat flour was marketed under the brand name MILO. In 1938, NESCAF was introduced to the as the first gross coffee. Then, in 1947, Nestl merged with the MAGGI Company.Currently, Nestle is still having their principles, which to provide the best products throughout the world. As the leading Food, Nutrition, Health and Wellness Company, Nestl provides the best food for anytime of day and for anytime of your life. Nestl has bounteous to become the worlds largest food company which offers more than 8500 brands and 10000 products throughout the whole world. With its headquarters in Vevey, Switzerland, Nestl has more than 456 factories in more than 80 countries and having more than 283,000 employers. (Nestle Products Sdn Bhd , 2010) l iteral impact of globalization on NestlePESTLE analysis which contains of political, economic, social, engineering science, legal and environment analysis which consist of external environmental. It is a useful analysis to understanding the situation of a company in an industry.Political analysisThe stability of political in a country allow be under the comity by NESTLE to build a plant that can operates NESTLEs factories that considering the countrys political stability, good tax incentives as well as its skilled workforce, NESTLE chose Malaysia to be the site of another regional manufacturing centre for NESCAFE (Mr. Jos Lopez, Executive Vice President, Nestle S.A. responsible for global operations and GLOBE (Nestls Global Business excellency Programmer)).Economic summaryThe important of economic factors will leads to the strength of consumer spending. For example, in recession economy, people might cut of their budget to consume household occlude rather than unnecessary stuf f such as chocolate. Americans likes luxury chocolates, a new premium line of cacao which is called Nestle Treasures God had launched in order to cash in on the recession.Social AnalysisEven though Nestle as a multinational corporate which operates their business in the other country, but do respect to peoples culture and traditional which is a corporate that think global, act local by working hard to integrate itself into the cultures and traditions of the country. For example, Kit-Kats linguistic rule is almost different everywhere. A Russian Kit-Kat is smaller than a Bulgarian, but less sweet than Germanys Kit-Kat. While in Japan, the strawberry Kit-Kat is all the rage.Technology AnalysisAs the technology of recently swapd rapidly in global, Nestle have attracted people to purchasing their products by using advertising. For example, Kit-Kat have been propoundd by attracting minor or child because it is a sweeten tid-bits. Infants foods advertisement is to attracted housewife to purchase it to given their child a healthy life.Recent research on technology analysis (Nestle Policy and Environmental sustainable) (2008) reports shown that during the manufacturing process, Nestle had using efficient technologies to ensure that there is no wasted energy while producing products. In addition, to control the bear away emission including the greenhouse gases.Legal AnalysisIn 1996, Nestle was the first multinational corporate that voluntary for Halal evidence for its own food products. Those food products that exported to the other countries were certified as Halal products. As a global food company like Nestle, hygiene is a must. Since Nestle has the Halal certification and hygiene was the procedure which contain in that certificate.Besides that, health and safety were the principle that keeps by Nestle. While provided employees to minimize risks in their personal lives, Nestle had always emphasize each of their employees about to change the employees attitudes towards personal safety.Environmental AnalysisNestle always committed to people to produce the best quality to their consumers. Besides that, Nestle also prevented the wasted food by reduced the materials weight and volume, yet supported initiatives of recycle from used compactaging. Nestle have also use recycled materials to produce its products.But, Nestle had done a fact that will cause of the lost of the home for orangutan. According to Heidi Marshall (2010), Nestles product-Kit Kat is a product of environmental destruction. This is because of the material that used in the candy bars and for the other Nestle products as well was comes from a palm oil that get from by destroying Indonesia rain forests.The system that used by Nestle to actual impact of globalization are includedMarket Penetration StrategyMarket penetration strategy is which to look up to increase market share of the current products. A firm using this method by raises their sale revenue without any changing of their existing products. Nestle may try to use the promotion which is buy 1 free 1 for its products. For example, buy 2 packs of 1kg Milo free a 10 pack of instant Nescafe.A market penetration will also involve the 4ps which is products, price, promotion and place. According to (Stuart Wall SonalMinocha and Bronwen Rees, 2010), the product in international marketing is the finis to which a standard and differentiated product should be provided. For example, Nestle is using the differentiated products since it produce its products Kit-Kat in different flavor. A Russian Kit-Kat is smaller than a Bulgarian, but less sweet than Germanys Kit-Kat. While in Japan, the strawberry Kit-Kat is all the rage.The international price is related to the account market different between countries, exchange rates, difficulties of voicing and collecting payment across borders, the effects of tariffs and purchase taxes on competitiveness, governmental regulations of the host country and the long ter m strategic plan of the company in the different markets in which it operates.For the promotion, it is often expressed to attracted people to consume their products and yet to capture a new consumer to purchasing their products. Nestle is always advertise their products thru media ways. To make sure that people know their products yet to pursuing people to make a purchase on their products. For example, Nestle advertise its products thru the television advertisement. This can make sure that children will attracted by its advertisement while it advertise.A place or distribution it is difficult to control from outside the oversea country itself. A company will solve this problem by its own subsidiary. In addition, if the products are being imported, a multinational company will heal a local agent to ensure that there is safety, cheapest and quickest way is using. For example, Nestle might recruit a people that located outside of overseas of it country to solve the problem such as a w arehouses, the selling markets and etc.SWOT Analysis of NestleAs Dr. Jill Novak, (2009) commented thatStrengthNestle is a global food producer since it located in over 100 countries. It is consistently one of the worlds largest producers which with global sales in 2008 topped $101 billion. In addition, Nestle was named one of Americas Most Admired Food Companies in Fortune magazine. Furthermore, Nestle provides quality brands and products and line extensions that are well-known, top-selling brands including Maggi, Haagen Dazs, Kit Kat, Nescafe, CoffeeMate, prepared baby foods, yogurt, foods for infants and many more.WeaknessMost of the products have their own weaknesses. For Nestle, it was not as successful as the other country in France. Nestle could not compete against a strong and established brand which is Dannon that entered into France earlier than Nestle which is top selling of health yogurt. Besides that, since 2004, Nestle has been forced to reduce the amount of sugar in th eir products that may cause of diabetes among American children. In addition, Nestle has been removed the packaging and advertising that false claims of heart healthy and lower cholesterol which is an order from FDA(Food and do drugs Administration) and American Medical Association which is the under fire of the breakfast cereal industry.OpportunitiesIn today, everyone hope and needs to have a healthy life, as a producer like Nestle, it has an opportunities to raise their selling profits with producing health-based products. Since Nestle was a well-known branded, for sure, it will be easy to attract people to purchase their products. Further, they launched a new premium line of cacao called Nestle Treasures Gold, in order to cash in on the recession economy in which consumers cut post on luxury goods, but regularly indulge in candy and chocolate. Americans want luxury chocolates, and high-end chocolate is immune to the recession (so far), because it is an inexpensive indulgence.Thr eatsEven though Nestle was a big producer in the world, but it still has its competitor, such as Hersheys, Cadbury-Schweppes (owned by Pepsi), Kelloggs, Starbucks, , Quaker, Kraft Foods, Danone, , Heinz, Unilevel and many more. Furthermore, any contamination foods allow for especially e.coli which causes the recalled of their brand-Toll House cookie dough. Outbreaks were linked to 28 states and the product had to be recalled globally. Nestl has yet to find out how this happened, and is still investigating (Dr. Jill Novak, (2009).Potential impacts of globalization on NestleNestle corporate have its own potential in globalization since it is a big foods producer in global.TechnologyIn the world of today, technology will be changing rapidly in global. And this will leads a good improvement in all type of products that will be produce around the world. A research and development department will be a part of Nestle from today towards future achievement by gaining profits without wasting the raw material in manufacturing process. Besides that, by using a developed technology may reduce the effects that will occurs greenhouse effect. For example, use of plastics packaging in every single of Nestle products improve to recycled paper packaging, used of plastic bottle in filling the Nestle beverage into tin that can recycle use.On the others side, a case that occurs in India, which is Nestle chocolate, will be melted before its eyes. This is because there are lacks of distribution and the heat temperature in India will make the chocolate melted. By using the technology that can solve this problem that is using the technology to change its chocolate ingredients so that can afford India heat temperature.EnvironmentalAs the info below, Nestles Kit Kats was made from a palm oil that came from by destroying the rainforest in Indonesia. This is cause of the pollution in Indonesia. To solve this problem, Nestle corporate should consider using the palm oil from the other count ries by not destroying the rainforest of the country. On the other side, there is another solution too. That is, refining the vegetables oil that can out inside the ingredient of making chocolate.SocialAs a food producer in global, Nestle may do some different in their products. Such as, a new flavor of the chocolate could be launch. This is because different country has a different taste towards foods. For Malaysia, a durian can be a part of the ingredient in the making of Kit-Kat. For Korea, a Kim chi flavor Kit-Kat can also create. This is a try for Nestle to attract people by producing different flavor but same products around the world.The strategy that might use by Nestle in the potential impacts on globalization isDiversification strategyAccording to Stuart WallSonalMinocha and Bronwen Rees diversification strategy involve the company branching out into both new products and new markets. For example, from the info that I mention below, Nestle might create a different flavor o f Kit-Kat to attracted new customer. For Malaysia, Nestle may create a durian flavor Kit-Kat to attracted those customer who are not chocolate lover but is a durian lover to purchase this products.ConclusionOn the day Nestle was introduced, it was only food for infants. As time goes, Nestle has grown to be more famous in brand name and focus in widen its product line. Today, Nestle is one of the most famous and successful foods and drinks producer. Furthermore, Nestle had expands to globalization which consist of factories around the world. Besides that, Nestle will always try counter threats and competitor, such as the current products or new product entrants. Therefore, Nestle still has the potential to grow more and continue to be the one of the leader in the market share.

Do Mergers and Acquisitions Fulfil Desired Objective?

Do Mergers and Acquisitions Fulfil Desired Objective?Do Mergers And Acquisitions Fulfil Their Desired Objective? And How People be Affected By the Result of These Mergers?DissertationTable of Con decennarytsCHAPTER ONE INTRODUCTION1.1 BACKGROUNDRestructuring of a firm has become a major compass of honor in the financial and economic environment all over the world. A comp all may convey internally, or externally. The aim of the commission is to maximize the profit. almost firms grow with internally which take place when firms existing divisions grow through normal capital budgeting activities.(S.Vanitha 2007) The industrial restructuring has raised essential issues two for the business and for public moreover jointure and skills may be critical to the strong expansion of business firms as they evolve through consequent stages of growth and development and most beta for new product securities industrys by a firm may require M and As at whatsoever stages in the firms de velopment . The victoryful competition in international commercializes may depend on capabilities obtained in a timely and skilled fashion through M As. (M Selvam 2007)Merger and learnednesss continues to experience dramatic growth. Record breaking mega unions conduct become popular in the world. In the last ten days and onwards just about of the titanicst spinal fusions and accomplishments took place in Europe. This was underscore by the fact that the bombasticst deal of all time was a hostile acquisition of a German comp some(prenominal) by a British firm.(Beena P.L 2000)Since the start of twenty first century the character of blend inr and acquisition even more park in the economical growth. It becomes even more global especially in Asia, Latin and South America. Over the past quarter of the century we have sight that merger waves have become longer and more frequent in wreakween shrunken as well when these trends combine with the fact that MA has chop-chop spr ead across the modern world, we see that the field is increasingly becoming as ever more important initiate of the worlds of incorpo pasture finance and embodied strategy. (Canagavally , R.2000)Merger and acquisitions are plays very important part in corporate strategy. They are the interesting and controversial tools if the firm do not want to grow internally by capital investment and it feces affect the shareholders wealth of both the firms (Legare.1998). The management of the grade companies is worried about their contemplates that squeeze out be modify the cost reduction strategies consists of reduction in labour force (Gould, 1998) the strategies at both local and national levels are important and concerned at legal proceeding in their industries. e.g (defence utilities etc.) Customers and suppliers are interested , as they want to know who they volition be dealing with in the incoming (Buono. 2003). All the big deals are because reported in the media, receive a big ger coverage, and get the attention of the public as well.People are very important part of every face but due to the increasing numbers of mergers between the companies they are largely affected and most of them get caught up in a merger or acquisition-by chance, Many of the people after working cardinal to five years stream are losing their jobs and facing severe reductions in status and certificate of indebtedness and, in general, being confronted with major questions about their careers, As a result , at times we are unsure whether our own beliefings about what is happening to these individuals are biasing our interpretation of what is going on. In this project the writer going to research on mergers between the professional services firms.According to Steven et al (2000) mergers and acquisitions decisions that are undertaken establish on financial analysis, influence and legal positions , However , it has been proved by a number of researchers that factors like informal po wer, low productivity , poor attribute , reduced commitment , hidden costs and voluntary turnover prevent the combined banks from reaching expected execution levels (Legare 1998). This is the reason that many companies face difficulties whence they pass through their post- desegregation processes (Buono 2003)According to Catwright Cary (1995) that mergers and acquisitions should be seen like marriages where both parties testament is very important for the success of new entity. At the time two diverse companies decide to come together as a result of MA drill, then the levels of instability in the macro and micro environment of both companies is challenged. So it is on that pointfore been proposeed that companies should chose the most appropriate merger and acquisition process and strategy. However Buono (2003) has suggest that each possibility has its own postures and weaknesses and therefore context of MS and its briny objectives play important role.Cartwright and Cooper has pointed out that MA depends upon combination of colligated functions like integration of people, systems, practices and culture. The critical review of the literary productions has recommended that most of research has been foc apply at studying single characteristics of MA in isolation. that the dynamics of MA variables that stupor on success and failures ratio has not been undertaken in the literature and there is a gap for research.This study will be focus to explore the major drivers and variables and their assemble on the success of merger and acquisitions across industries from a corporate strategical perspective.1.2 Rationale behind ResearchMergers and acquisitions is angiotensin converting enzyme of the common strategies in todays business world. Gould (1998) has conducted a survey involving 12000 managers from different countries and concord to the result of his survey more then 1000 companies were involved in acquisitions or a merger in two years between 1995 and 1997.moreover merger and acquisitions has become the leading strategic options. However, the performance of the combined companies has been lower than expected. According to Buono (2003) the basic drivers of MA only involved in financial, operational and strategic aims and objectives. So therefore my main area of focus of this research is to explore the major drivers and variables and their effect on the success of merger and acquisitions across industries from a corporate strategic perspective.1.3 Aims and ObjectivesThe basic aim of this project is to understand whether mergers and acquisitions always fulfil desired objective. The aims specific areas are as follows.To explore the major variables that conflict on the success of merger and acquisition different industries from a corporate strategic perspectiveTo explore the corporate strategy in achieving desired results from MA activitiesTo evaluate the impact of the mergers on an employees and examining the programmes for deal ing with separation anxiety for employees.1.4 Dissertation StructureThe official Structure of the dissertations is being applied which is provided by the university and analysis has been done which suit the story and the objectives of the research. The structure of this report is summarized as followsChapter 1 Introduction of the research topic and lays the basis for the rationale of selection of the theme under scrutiny. It introduces the effect of MA on business and effects that they expected. The chapter also summarizes the rationale for selection of topic and states the aim and objectives of this research.Chapter 2 Consists of review of the literature that has been produced in the subject area of mergers and acquisitions and their desired effects for companies. It has highlighted some of the highly respected literature in the field of aims and objectives of this research.Chapter 3 Provide the methodology and strategy adopted by the researcher to undertake this research. It poi nts out the specialism and weaknesses of using different data collection mechanisms and has shown how they fit in the larger context of aims and objectives of this research.Chapter 4 very important chapter consists of analysis and findings regarding the importance of strategic concurrence within a merger or an acquisition activity with the help of a project of case studies. The chapter developed recommendations for companies under the light of macro indicators, theories and qualitative data gathered through this research.Chapter 5 provides a comprehensive conclusion from this research and gives a list of recommendations for companies that can be drawn from this focused research.Chapter 2 Literature ReviewIn this chapter an exploit has been made to briefly review the research already undertaken and methodology employed moreover the study has been produced in the domain of aims and objective of the project and it has been divided into number of different sections so that reader un derstand with ease.2.1 OverviewConcept of Merger and AcquisitionOver the last few years different companies have engaged in domestic and international mergers and acquisitions to match the macroeconomic trends operating on a worldwide scale in the market place. Up till now the ultimate success of a companys global strategy may depend on how well it manages the insecure gracious resource fit issue associated with strategic customer cantered decisions and strategies. The literature presents the understanding and resolving interpersonal management issues that result from organization, aggroup, and individual misalignments. An actual merger and acquisition integration project is used to discuss the application of this hail (Thomas L. Legare in his paper Understanding and Managing Human Resource Integration Issue) M A defined by Arnold (2002) as combination of two firms of roughly equal size on roughly equal terms and in which the shareholders last out as joint ownersM A activitie s in late 20th centuryIn 1960s Mergers and acquisitions first became an important topic within the organization management meetings. It is usual to consider merger and acquisition in terms of the extent to which the activities of the acquired organization are related to those of the acquirer. The most common classification proposes four main types (Walter 1985 Hovers, 1973 Kitching ,1967). These being1- VerticalThe process in which two organizations combined within the same industry.2- HorizontalThe process in which two similar organizations combined within the same industry3- ConglomerateIn this process acquired organization is in completely different field of business activity4 concentricalIn this process the acquired organization is in a different but related field in to which the acquiring company merge its business.According to Schweiger and Ivancevice, 1987 mergers and acquisitions can be considered to differ in terms ofMotive and transactional typeThe envisaged degree of int egrationCommon objectives behind M ActivityAccording to Napier (1989), in a review of the literature, draws the distinction between financial or value maximizing motives, and managerial or non value maximizing motives. Mergers known as financial or value maximizing motives when the main objective is to increase the profit and decrease the risk involved in business moreover non value maximizing motives relate to merges which occur primarily for some other strategic reasons ( Halpern, 1983). Moreover according to handy (1993) creation of shareholders value is the underlying aim behind any MA activity. However , there is a range of strategies involve to improve financial performances and consequently increase shareholders value.According to Marks, (1988b). There is split of risk involved in activity like Mergers and acquisitions involving the collective annual investment of billions of pounds and affecting the working lives of millions of employees. It has been recommended in future that 50 to 80 per centum of all mergers are considered to be financially unsuccessful (Marks 1988b), most probably in financial return, represent at best an each way bet(Lorenz, 1986)The popularity of Merger and acquisitions is still strong despite of the fact that it has been frequently fail to achieve the financial growth (Hovers 1973 Farrent 1970 Jemison and Sitkin, 1986). Indeed there is dozens of evidence that Britain and the regular army are currently experiencing an unprecedented wave of merger activity (Morgan, 1988 Hughes, 1989). In the last 10 years , there have been over 23000 registered acquisitions in the ground forces , and before the end of this decade one in four of the Us workforce will have been affected by merger activity ( Fulmer, 1986) with the approach of 1992 , a similar trend is predicted for Europe.The Merger and acquisition is facilitated by number of factors.Market ConditionsMarket conditions are changing day by day and in this environment there is a need to consolidate or capture new market so strategic mergers and acquisitions become more attractive and opportunist alternative response to the setting up new outlets, and at the same time provide a tool to finish the competition ( Meeks , 1977)Increasing accessibility of CapitalMergers and acquisitions activities has been increased because the organization and financial institution may need of capital from outside countries because of low interest rate.More companies for sale.There are lots of companies come in to the market because of number of reasons like successful entrepreneurs of the post war years reach retirement age , because of families issues and there is not inbred successor within the family.The Easing of Regulations.According to McManus Hergert, 1988. Gartrell Yantek suggested that acquisition activity is related to political climate in that right of centre administration stimulate activity.The hold to share RiskMergers and acquisitions is very important if u need to share risk like new product development often results in the formation of joint ventures , mergers and other types of strategic alliance.The existence of complex Indivisible ProblemsAll of these can be considered to be logical economic and marketing factors, which make viable the decisions to acquire, These conditions , particularly the need to share risk and problems solving, have also contributing to the increasing trend towards the formation of joint ventures and Mergers (Harrigan, 1988)(vii) Unrecognized Psychological MotivesAccording to Levinson (1970) suggests one such motive to be apprehension of risk McManus and Hergest (1988) suggest that the decisions happens when CEO is blase and wants to find a new game to play or to bring out some excitement amongst senior managers (Hunt, 1988)2.2 Impact of Mergers and AcquisitionsMerger and Acquisitions have the prime aim to maximise the firms profit and shareholders wealth like any other strategic growth option, but ther e has been a risk of failure so the debate in the literature among theorists and practitioners as to the real strength of the strategy in creating shareholders value worth the risk of failure. The review literature that surrounds different prospects like shareholders, acquirer , targets has been studied on unretentive , medium and long term value creation through the MA activity . The following different categories of studies can be highlighted.Affect of MA Activities on PeopleThe Human Side of Mergers and Acquisitions is about to impact that mergers and acquisitions have on people in the workplace the psychological difficulties that people experience, the culture clashes that can appear in organizations that can emerge in organizations during the post merger integration period, and the ways in which these problems can manifest themselves such as communication breakdowns a We-they mentality between the component organizations in a merger, lowered commitment , drops in productivity , organisational power struggles and office politicking , and release of key organisational members. We adopt primarily and organization development (OD) perspective on mergers and acquisitions given the myriad problems (Thomas L Legare)The Existing evidence on the effects of mergers and acquisitions on power or value comes from two basic types of large sample studies event studies and performance studiesEvent studies consider the returns to the shareholders of targets and acquirers in the days before and after an acquisition announcement .These studies consistently find that the combined returns to acquirer and target stockholders are unequivocally positive .These positive returns imply that the market anticipates that acquisitions on average will acquire value. These studies and reactions do not, however, provide insight into the sources of the value changes in mergers or whether the expectations of value changes are ultimately realized. Furthermore, the combined returns cover a broad range of responses from very positive to very negative.Cross sectional collapses of event period returns provide some evidence that the broad range of combined announcement period returns reflects the markets ability to forecast an acquisitions success. For example both Mitchell and Lehn (1990) and Kaplan and weisbach (1992) find the there is a relation between (1) acquirer and combined returns and (2) the ultimate progeny of the acquisition. Other studies examine a number of different determinants of the cross-sectional variation in returns associated with acquisitions. (see e.g Lang , Stulz, and Walkling 1991 . Maloney , McCormick , and Mitchell 1993 morock, Shliefer , and Vishny 1990)These Cross-Sectional analyses of event period returns provide some understanding of the nature of the market reaction to acquisition announcements.They do not , however , examine whether the anticipated value creation or improved productivity materializes, Nor do they have a great deal to say about the organizational mechanisms and management practices that drive acquisition success or failure.Studies of post merger performance undertake to measure the longer-term implications of mergers and acquisitions using both key outing and stock return data. Studies of accounting data fail to find consistent evidence of improved performance or productivity gains. (see e.g, Healy , Palepu, and Ruback 1992 and Ravenscraft and Scherer 1987) similarly , studies that focus on acquirers long term stock performance find mixed results deviantly negative stock returns after the acquisition ( agraqwal , Jaffe, and Mandelker 1992), no antidromic returns (franks , Harris , and Titman 1991) and negative abnormal returns only for stock mergers (Mitchell and Stafford 1996) Like the announcement period event studies, longer term performance and event studies written document substantial cross sectional variation in performance , but do not study the sources of value changes in mergers and acquisitions.In sum , there are a number of questions that the existing economics and finance literature on mergers and acquisitions leaves unanswered , Existing work provides mixed results on the average impact of mergers and acquisitions More importantly , existing work offers little insight into the determinants of an acquisitions success or failures.Research on the basis of Capital MarketCapital market is one of the research category used as central information point. According to Healey (1992), the stock market data reflects the effects of MA as it reflects future profits and dividends expected by the post integration entity moreover these researchers believe that the result has been found swayed by the researchers personal orientation an hypothesis. It is been analyse that majority among studies that have been covered lower then desired effects created through analyses based on capital market data.Event Study methodological analysisAccording to data et al (1992) have indicate d that these studies are based on the hypothesis that markets across the industrialized world are highly well-organized and therefore in short after the MAn announcement moreover it depends on the future financial benefits or losses. The result of such studies have highlighted the majority of MA activities do create affects that can range from significant to normal (Sudarsanam 2003) but the people working along with the field and many other critics have argued that the methodology is only emotional for small projects to obtain the desired affects and does not represent long term desired affects in the medium to long term.Short Run ObjectivesA large number of organizations plan for financial gains within a short period of time when the merger date is finalized they are looking to achieve this objective, 30% and 10% abnormal returns have been found for the target shareholders Sudarsanam et al (1996)Long Run ObjectivesAccording to Agarwar (1992) the organizations long term desired aff ect through MA activity that has gained an increasing interests among researchers after the data is available for the last wave of MA in the 1990s. There has been a mixture of results as- 10% abnormal returns over 5 years MA periods Fama French (1993) showed positive 9% abnormal returns for the acquired and negative -4% abnormal returns for the acquirer and sudarsanam Mahate 2003 showed a range of negative -18% to positive+1% abnormal returns in MA situation. Although it has been found out that many of these studies have used different models, benchmarks and organizational data, but there is a general consensus that MA abnormal desired affects in the long term.Operational Planning ResearchThe best way to analyse the affect of MA activity is to study the operational performance of the firms involved. The operational data consists of accounting data like cash flow and profit and loss statement are used by such studies (Healey 1992) Herman and Lowenstein (1988) used these technique o n data gathered during 1975 to 1983 and found that no significant improvements in the performance of post MA entities. Healey et al (1992) found a meagerly 3% operational performance among companies analyzed. However the same data was later analyzed under improved methods and found no operational performance. The results show large number of failures in creating substantial desired affects through operational analysis.Recent Merger and Acquisitions trendsIn the above table shows the recent trends in the field, let us being with our full dissertation of the subject of MA. This will be begin with a discussion of the basic terminology used in the field.2.3 MAJOR strategical ISSUESAccording to Cartwright and Cooper (1995) in company to get the desired objective during the MA activity the internal environment of firms should be synchronized. It can therefore recommend that integration of people, their systems, procedures, practice and organizational culture is extremely important in o rder to get the desired objective.Mr David (2007) suggest that the internal aspects of firms that are going to merge can be divided into two core competencies that can help to minimize the factors involved the failure of MA strategies.These core competencies lie in the field of corporate strategy which usually lack coordination during MA activities. The main limiting aspects of MA in terms of strategic importance that can play a vital role by using their core competencies have been highlighted as followsorganisational cultureThe cultural differences is the single largest cause of lack of proposed performance, achieving the desired target and objective and time consuming issues in the running of successful business ( Bijilsma frankema , 2001) according to him culture plays a important part in employees motivation in the development to new business he says that cultural clash is the most dangerous factors when two companies decide to combine moreover the things like styles , values an d missions is the part of factor influencing the MA.According to (Covin et al, 1997) the employees required five to seven years after the merger to feel truly incorporated. Due to the multitude of these changes many problems arises like loss of job, also financial debt and fears of jobless.(Mirvis and Marks 1992) moreover he says that after merger the new team is also di focussinging and anxiety for the people other fear include the loss of effective and close team members,as well as the uncertainty about the new team members and supervisors to be inherited the employees when force to deal with new team members and managers they may develop fears of taking risks and raising sensitive subject. This may adopt us verses them thinking, where trust for the new team members will be minimal (Mirvis and Marks, 1992).Management facing this kind of behaviour may have to pay the high price of loss of coordination and initiative among the employees of the new business combination. Moreover the issues and disagreement will be more difficult to resolve, so the time after the merger is the most difficult time for the management and new team members to move forward as a whole. Appelbaum etal, (2000)StressAccording to (Datta et al , 1992) the process of merger and acquisitions consists of biggest change at the individual and organizational level in the recital of organizations because of this the process is stressful. When one culture combines with another the employees feel as through they have lost control over important aspects of their loves, and in an attempt to regain control, they often withdraw. So it creates stress within individual , i.e reduced performance and job satisfaction . ( Berger and Ofec 1996)According to Schweiger Denisi (1991) the employees after the MA go through a time of increased anxiety uncertainty and stress. They are concerned about their new position it will create more stress in them so communication plays the vital role during the merger so t hat employees know what is going on and how they might be affected during and after the post integration period. Thus it can be suggested that while negotiations have been compared to flirting before marriages , and the closing of the deals to forming a new family , employees reaction can be associated with bereavement (Katinka , 2004)Organizational change and resistanceChanges after merger announcement like stress, symptoms, work related factors, health status, and lifestyle. Personal characteristics were composed of age, sex, height, weight, and marital status in both surveys. Moreover stress related symptoms like anxiety, impatience and depression were dichotomized by either having a complaint or not so following a MA , a complex set of organizational , managerial and personal changes or inevitable.Jensen Rubock (1983) claim that in order to cope with the changes and resist with the changes there is a way to select a strategy and a set of specific approaches for implementing an organizational change effort. It is very important for managers to implement changes successfully in order to cope with the changes. The researchers have introduced six different strategies in order resist the changes after the merger and four major reasons why peoples resist changes.Image, Identity and corporate trustAccording to (Ravenscraft and Scherer 1988) image , identity and confidence of the human resource may reduced after the combination process it has been send that most of the employees will feel uncertain and will need some relaxation environment .It can be recommended that the peoples effected by this process can prove dangerous for the management they can change the ownership moreover the employees who are affected by the process tend to protect their identity and confidence through tolerance and subdue and hence they try to maintain their status and confidence with experience that they are the part of new entity, if the cultural factor is not adequately taken into account at this stage of the merger , there will be so less time to contain it after the merger.Weston et al (2001) discuss the fear and stress associated with a merger. Schwert (1996) argue that when the objectives after the merger are not met , the managing teams of both companies are the employees of the acquired company enter a cycle of escalating and distrust. In other words, managers of the acquiring company press for increased control, while employees of the acquired company resist and demand their autonomy. Others view mergers and acquisitions as power games , which create some excitement fro bored CEOs.CommunicationTompkins (1984) defined organizational communication as the study of sending and receiving messages that create and maintain a system of deliberately corresponding activities or forces of two or more personsOrganizational communication is the exchange of messages through collective creation maintenance and transformation of organizational meaning. Members develop commonly understood patterns of expectations of organizational action through communication. Moreover communication with the employees is a very important factor throughout the entire MA process and creates a positive effect on employees through the trying time.According to John et al (1999) that communication plays a vital role in the combination of different and various cultures. The cultures can be at conflicting ends and therefore should be understood by the top management during integration period moreover according to Richard et al (1999) the human resource department should plan for the change in organization and they should know before this process that what going to happen with the company when two cultures combine as the result of merger. So in the process of merger only decision is not enough but the proper communication of these decisions among the company is very important moreover management works horizontally and vertically through leadership, control and organizatio n.(Sudarsanam and Mahate, 2003)FLOW OF CASHDespite of the fact that many people loss their job in the process but the same time high rate of voluntary turnover linked with the process moreover it includes substantial outflow of endowment fund and expertise. According to Ravenscraft and scherer, 1988) report executive turnover rates as high as 75% in the first three years of post acquisition period. Unplanned personnel losses are not necessarily confined to the more senior levels of the organization. Typically, acquired or merged organizations experience on overall rate of staff turnover of at lest 30% in the first two years post merger period (Cartwright and Cooper 1995)2.4 Success and FailuresA large number of mergers and acquisitions are unsuccessful .Over the last fifteen years, 23% of all merged firms worldwide reported lower profits than comparable non-merged firms (Gugler et al.(13)) Daimler Chrysler, the effect of the largest industrial merger ever, for example , has only po sted low or negative profits since its birth in 1998-including the biggest loss in German business history in 2001. The disappointing results of mergers have been puzzling commentators and academics alike.In the management literature, poor merger performance has often been connected to unsuccessful addition of different corporate cultures. Cultural differences, however, are not enough to explain failures. First, firms seem to be aware of organisational difficulties when taking merger decisions. DaimlerChrysler, for example, anticipated post merger Challenges. Second, mergers between partners with imminent corporate cultures sometimes perform worse ( Morosini et

Peptidylarginine Deiminase and Neurodegenerative Diseases

Peptidylarginine Deiminase and Neurodegenerative DiseasesAbbreviationsAD Alzheimers disorder central nervous system Central nervous systemGFAP Glial fibrillary acidic proteinNFT Neurofibrillary tanglesMAP2 Microtubule-associated protein 2MBP Myelin basic proteinNef3 Neurofilament 3PAD Peptidylarginine deiminaseRT-PCR bowl over transcriptase-polymerase chain reactionSP Senile plaqueIntroductionNeurodegenerative diseases, much(prenominal) as Alzheimers disease and Multiple Sclerosis, are a group of progressive conditions, which affect a persons learning abilities and the day-to-day routine management. Citrullination/deiminasion is a process describing the enzymatic involvement in conversion of arginine residues into citrulline in target proteins. Here, is a re look, entailing the main features of the peptidylarginine deiminase (PAD) enzyme family, with a view on its history, social movement and future in neurodegenerative disorders.BackgroundThe amino acid Citrulline was firstly me ntioned in 1955 (Smith and Young), and the citrullination process of L-arginine conversion to L-citrulline was firstly described in 1958 (Rogers and Simmonds).Citrullination is a posttranslational process, and alike results in a 1Da decrease in size, due to an hydrolytic reaction (Vossenaar et al., 2003 Gyorgy et al., 2006 van Venrooji and Pruijn, 2003). However, it was only in 1977 when peptidylarginine deiminases, the enzymes that are responsible to the citrulline modification, were firstly described (Rogers et al.).Alzheimers diseaseGFAP, an astrocyte-specific marker protein, is involved in the progression of Alzheimers disease via PAD2 citrullination. The increase of PAD2 can be seen in the hippocampi of AD patients. GFAP and vimentin citrullination was also identified by using a 2D gel electrophoresis and MALDI-TOF mass spectrometry. Activation of PAD occurs upon a mass influx of Ca2+, and therefore an increase in citrullinated proteins (Keller et al., 2000 Maccioni et al., 20 01). The PAD family consists of five know members (1-4 6), each is present in a different area in the homo body. PAD2 and PAD4 area of activity is the central nervous system (systema nervosum centrale), although PAD2 in bigger amounts than PAD4 (Kubilus and Baden, 1983 Watanabe et al., 1988 Terakawa et al., 1991). Yet, the role of the different PADs is still largely understood. PAD3 was found in the root sheaths of hair follicles, as part of the citrullination process of keratinisation (Kanno et al., 2000). PAD4 was found in human myeloid leukemia HL-60 cells, and later in peripheral blood granulocytes (Nakashima et al., 1999 Asaga et al., 2001). PAD2 and PAD4 are also present in the myelin sheath. In fact, hyper-citrullination of myelin basic protein (MBP) is now know to result in myelin sheath loss in multiple sclerosis patients (Moscarello et al., 1994 Wood et al., 2008 Musse et al., 2008). Moreover, PAD4 is also involved in histone deimination in brain tissues of such patients (Mastronardi et al., 2006). Following immunocytochemical studies, PAD2 have been detected in glial cells and astrocytes (Asaga and Ishigami, 2000 Vincent et al., 1992 Asaga and Ishigami, 2001), microglial cells (Vincent et al., 1992 Asaga et al, 2002), oligodendrocytes (Akiyama et al., 1999), and Schwann cells (Keilhoff et al., 2008). Furthermore, during hypoxic insult (Asaga and Ishigami, 2000) and during kainic acid administration (Asaga and Ishigami, 2001 Asaga et al., 2002), neurodegenerative regions shown to have PAD2 activity and deimination of various proteins. These findings suggest that PAD2 plays an important role in protein citrullination in neurodegeneration.Senile plaques (SPs) and neurofibrillary tangles (NFTs) are the two main forms of protein aggregation, and therefore responsible for neuronal death in AD (Katzman, 1986 Smith, 1998). They are mainly found in the hippocampus and cerebral cortex, when levels of PAD2 were detected to be more than threefold higher in th e hippocampus than in the cortex of rat brains (Asaga and Ishigami, 2000). A study by Ishigami et al. (2005) was set to evaluate the involvement of protein citrullination in AD patients brains, and identified two citrullinated proteins- GFAP and vimentin, by using a two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry. It went on to identify also a citrullinated MBP, again in the hippocampus region of the AD patients.Multiple sclerosisHigher rates of citrullinated MBP were found in the CNS of MS patients than in the CNS of healthy adults (Mastronardi et al., 2006 Nicholas and Whitaker, 2002 Raijmakers et al., 2005). However, similar levels of citrullination have been observed in children under the age of 4. An indication that citrullination is involved in the development of get on with myelin (Moscarello et al., 1994 Wood et al., 1996). Due to known increased citrullination, PAD2 and PAD4 rates in myelin from normal-appearing white matter (NAWM) of seven MS patients were examined, and were found to be significantly higher compared to NAWM from cardinal subdue individuals, using immunoblots with PAD2 and PAD4-specific antibodies (Wood et al., 2008). The anti-citrulline antibody- F95, was also used in the same manner, resulting in the same outcome (Nicholas et al., 2004). The study by Wood et al. (2008) also discovered that PAD2 can citrullinate 18 out of 19 arginine residues, whereas PAD4 can only citrullinate 15 out of 19 arginine residues localised in MBP. It has been found and reported that MPB deimination increases its susceptibleness to degradation by proteinases, which are elevated around active plaques and in the cerebrospinal fluid (CSF) (Cuzner and Davison, 1973 Einstein et al., 1972 Richards and Cuzner, 1978). It has been also reported that macrophages and reactive astrocytes are able-bodied to produce the proteinase cathepsin D (Allen and McKeown, 1979 Prineas and Wright, 1978). Cathepsin D then produces peptides that contain the immuno-dominant epitopes of MBP, located in the CSF of MS patients (Whitaker, 1977 Whitaker and Granum, 1980). It was then discovered that different MBP strains, containing greater amounts of citrulline per mole of MBP than their counterparts were digested at a much faster rate by cathepsin D (Pritzker et al., 2000). An explanation for this discovery by Pritzker et al. can be explained by the three-dimensional atomic social organisation of the human MBP they created. The structure showed a clear correlation between the open conformation of the atomic structure and the higher rate of citrullination in-site, which allows cathepsin D a bankrupt access to Phe-Phe linkages in MBP, and so an increased digestion of citrullinated MBP.Current perspectivesIn addition to MBP, GFAP also have shown to be citrullinated in MS. In a study by Nicholas et al. (2004), GFAP citrullination rate in both the NAWM and lesions of patients with SPMS was compared with the white matter of control brain tissu e, and was found to be in higher amounts. The findings were obtained using GFAP anti-citrulline antibodies (such as P95) and confocal microscopy. On an elongated study by Nicholas et al. (2004), using dual staining wit GFAP anti-citrulline antibodies, it was found that lesions taken from nine MS patients were highly citrullinated compared to white matter taken from six healthy control individuals. Western blotting has also confirmed that the majority of the deimination occurred in GFAP. PAD4 is enable to translocate from the cytoplasm to the nucleus, due to its ability to carry a running(a) atomic localisation signal (Nakashima et al., 2002). PAD4 modification can also affect nuclear proteins, histones H2A, H3 and H4, and nucleophosmin/B23 (Hagiwara et al. 2002). Deimination of histones causes change in chromatin confirmation, and therefore gene transcription gets move off (Shimoyama et al., 2010). In a study by Cuthbert et al. PAD4 was found to inhibit transcription of estrogen -responsive genes in MCF-7 cells. Levels of PAD4 in MCF-7 cells were shown to rise in reply to estrogen, followed by deimination of the pS2 booster amplifier by PAD4, which coincides with downregulation of this gene (Cuthbert et al. 2004). Wang et al. showed that incubation of purified substrates H3 and H4 with PAD4 in vitro generated citrullinated H3 and H4, which coincided with a dramatic reduction in H3 Arg 17 and H4 Arg 3 methylation (Wang et al. 2004). This effect was also mimicked when HL-60 granulocytes were incubated with PAD4 in vivo, in the presence of calcium ionophore. PAD4 was found to be elevated in NAWM from 17 patients with MS, compared to 9 control subjects (Mastronardi et al. 2006). This was shown by fractionation of these samples into membrane-containing, non-microsomal, and nuclear fractions, followed by quantitation of the amount of PAD 1-4 antibody binding. The nuclear fraction contained a 3.5-fold increase in the level of PAD4 in patients with MS compared to controls. Through western blot analysis using anti-PAD4 antibody, this was attributable to increased PAD4 in the MS NAWM. Using an antibody against citrullinated proteins, this increase in PAD4 was found to be accompanied by an increase in citrullinated proteins in brain tissue taken from patients with MS, whereby grueling nuclear labeling in NAWM from MS patients was seen compared to controls (Mastronardi et al. 2006). This increase in PAD4 was also accompanied by an increase in nuclear histone H3 citrullination, as shown by immunostaining of MS and control tissue with an antibody against citrullinated protein, which revealed strong nuclear staining of cells in the MS white matter. These findings were confirmed by western blot analysis, which showed a great abundance of citrullinated H3 in MS NAWM, with only traces in white matter from controls. This citrullination of histones greatly affects the chromatin structure and function, as deimination of arginine residues of histones de creases their positive charge, which compromises its ability to interact with DNA and possibly resulting in apoptosis of affected cells (Moscarello et al. 2007 Wang et al. 2004). It is not known whether excess citrullination is a primary or a secondary event to the inflammatory process in MS or whether the regulation of PAD isoforms may be part of the genetic susceptibility to MS. Single-nucleotide polymorphisms in the PAD4 gene, also associated with the autoimmune disease rheumatoid arthritis, increase informational RNA stability, suggesting that this could result in greater PAD4 protein expression and hence increased citrullination of proteins (Suzuki et al. 2003). Increased PAD2 protein expression in human astrocytes in vitro has also been reported in response to increased intracellular calcium levels when cells were subjected to elevated pressure or in response to hypoxia (Bhattacharya et al. 2006a, b Sambandam et al. 2004).A number of pathological processes, including excitot oxicity, occur in the CNS of patients with MS, which would lead to raised intracellular calcium ions in neurons and glia (Shideman et al. 2006 Smith 2007). Large numbers of activated macrophages are present in inflammatory demyelinating sites inside MS lesions. Since these cells contain PAD enzymes and there is increased cell death due to raised intracellular calcium ions, this would lead to activation of PAD enzymes when released from decease cells (Bhattacharya et al. 2006a). Thus myelin proteins may be citrullinated both intracellularly, during myelin degradation following phagocytosis, as well as extracellularly, following release of PAD enzymes from anxious(p) cells. In addition, significant hypomethylation of the PAD2 promoter has also been found to occur in MS NAWM compared to controls, which may lead to increased PAD2 expression and subsequent increase in citrullination, as hypomethylation leads to increased gene transcription (Mastronardi et al. 2007).Future perspectivesCo nclusionIn the last 60 years since it was firstly mentioned, the research area of PADs have make a tremendous leap and came about with many important discoveries regarding the mechanisms and pathologies concerning PADs. However, it still searchs to be largely unknown and have many possible routes of research. Especially when considering the vast localisation of the PADs throughout the human body. Such areas of research may ask after the origins of the calcium influx to the brain tissues, and the timing of that physiological event how may the rate of calcium influx affect the rate of neurodegeneration what would prove to be the most effective PAD-inhibitor treatment, etc.However, looking at the milestones along the research of PADs, it does seem that the right questions are being asked, and that the available/emerging technologies are suitable for this research.ReferencesSmith, D. G. and Young, E. G. J. Biol. Chem., 217, 845 (1955).Rogers GE, Simmonds DH. Content of citrulline and other amino acids in a protein of hair follicles. Nature. 1958 182(4629)186-7. PubMed 13566234Vossenaar ER, Zendman AJ, van Venrooij WJ, Pruijn GJ. PAD, a growing family of citrullinating enzymes genes, features and involvement in disease. Bioessays. 2003 25(11)1106-18. PubMed 14579251Gyorgy B, Tth E, Tarcsa E, Falus A, Buzs EI. Citrullination a posttranslational modification in health and disease. Int J Biochem Cell Biol. 2006 38(10)1662-77. PubMed 16730216Van Venrooij WJ, Pruijn GJ. Citrullination a low-toned change for a protein with great consequences for rheumatoid arthritis. Arthritis Res. 2000 2(4)249-51. PubMed 11094435Rogers GE, Harding HW, Llewellyn-Smith IJ. The origin of citrulline-containing proteins in the hair follicle and the chemical nature of trichohyalin, an intracellular precursor. Biochim Biophys Acta. 1977 495(1)159-75. PubMed 410454Keller, J.N., Hanni, K.B., Markesbery, W.R. Impaired proteasome function in Alzheimers disease. J Neurochem. 2000 75436-439.Macci oni R. B., Muoz J. P. Barbeito L. The molecular bases of Alzheimers disease and other neurodegenerative disorders. Arch Med Res. 32, 367-381 (2001).

TO SPARE OR NOT TO SPARE: :: essays research papers

TO SPARE OR NOT TO SPARE THAT IS THE ETHICAL QUESTIONA twenty-something year old flannel male applied science learner travels from Prescott, Arizona to Friendsville, Tennessee during his summer and winter breaks from school. The length of distance covered in one trip is about 1800 miles. He drives a 1968 Ford Mustang. This political machine is in need of restoration, but is all-original. Because he is alone, this student cannot stop at anywhere that is not public. Even a Rest Stop is too tough for a lone traveler. This student driver does not even drive at night. The dilemma produces at the half-way point of the trip, the middle of the Texas pan-handle on Interstate 40 East. This area has few shove along stops and almost no rural or suburban areas. The student passes a political machine on the side of the road. This car is driving on a flat tire. Unfortunately the only safe option for this student is to continue down the road and pray for the person in distress. The student- driver stops for gas at the only stop for another 50 miles. Like most gas stops in this area, it stands alone on this exit. The student-driver pumps gas into his car and goes inside to pay for the fuel. As the driver is about to leave, he is stopped by a 60 to 70 year old Caucasian male. This man has a flat tire. He recognizes the car that passed him earlier and asks for help. This man recognizes that the Mustangs spare volition fit his car, and he proceeds to ask the student if he would be willing to part with his spare. The moral dilemma begins. If the student gives the man the spare, his guilt for passing the man will be extinguished and it will be replaced with the satisfaction of helping another human being from being stranded. However, this would leave the student without a spare tire for the last 900 miles of his trip. The three estimable systems being used to respond to this moral dilemma are Kantism, Utilitarianism, and Epicurism. In this dilemma, there are two choices, a nd each system has its own way to respond. Kant would begin by criticizing the analysis of the consequences, because consequential ethics lacks universality, leads to rules that violate our ordinary moral sensibility, and reverses the proper relationship between ethics and happiness.(Symposia. 2005.