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Social Transitions and The Rites of Passage Discussion

Social Transitions and The Rites of Passage Discussion.

In your own words, answer this unit’s discussion questions in a main post (recommended minimum 200 words.After you have reviewed the Assignment Details below, click the Discussion Board link under the My Work heading above to open the Discussion Board and make your post.Review this tutorial on How to Post to the Discussion Board.Assignment DetailsLifespan DevelopmentIn this discussion, you will discuss social transitions and the rites of passage that adolescents go through to “achieve” adulthood. Common in the United States are graduation, turning a certain age (16, 18, or 21), getting a driver’s license, and moving out of the parents’ home. Religious and culturally specific ceremonies might include Bar/Bat Mitzvahs, Christenings, and Quinceaneras. List 1 major rite of passage or event that you have experienced that marked your transition from one stage to another (for example, childhood to adolescence or adolescence to adulthood). Describe the following: Key features of this event The effects those features had on your transition The degree to which this rite of passage is universal in the United States What is 1 common social transition (rite of passage) that an individual may go through between late adulthood and death? Describe the following: Key features of this event The effects those features have on the transition The degree to which this rite of passage is universal in the United States Research and describe 1 rite of passage for any life stage from a culture different from yours. When replying to at least 2 peers, consider comparing your experiences to others’ and to other cultural rites of passage.
Social Transitions and The Rites of Passage Discussion

Introduction Assessing the economy of Asian countries that have marked the greatest improvement in terms of economic performance in the past decade, it is clear that the rapid pace at which the economy has grown is closely linked to their strong export orientation. Economic growth within these East Asian economies followed the change of economic activity from being based on the customary importation substitution towards activities and policies that are more focused on exporting goods to other countries. The result of such policies was immediate net annual growth of twenty percent and this extended over a long time period (Balassa, 590). The aim of this paper will analyze the similarities and differences between economic developments in Asian countries. Emphasis will be laid on the difference and similarities between first and second wave. Under the first wave, we will discuss in detail, three cases, namely Japan, South Korea and Taiwan. Under the second wave, we will also discuss three cases i.e. China, India and Thailand. First Wave of Economic Revolution Japan The achievement of export trade has always been closely linked to the general growth of Japan’s economic development. Volume trade averaged seventeen percent up to the year 1973. The net effect of export trade to Japan was not only limited to the provision of much needed foreign currency for the purchase of raw goods, but it also benefited the country through developing its industry so as to take advantage of the economies of scale that could not have succeeded if it was to rely solely on its domestic market. It is also through export trade that firms realized the threat of competition and the need to be innovative and efficient (Buckley, 45). So what are the catalysts for Japan’s success? The country’s industrial policy has always fostered a culture of innovation and support for local firms. Local firms are encouraged from the outset to aim for export of their products. Get your 100% original paper on any topic done in as little as 3 hours Learn More All this is done in order to ensure that the country is able to compete with the West when it comes to global trade. The industrial policies of Japan are aimed at offering not only financial support but also technical support that includes advisory services and arranging trade fairs all around the globe (Buckley, 67). South Korea Export trade in South Korea has mainly been catalyzed by two important key policies that were instituted by the Government. The first was land control: Land was redistributed so as to accommodate the rising population. At the time, there was a pending population crisis as immigrants flocked from the North. A family was only restricted to three hectares. The second policy that assisted the country was education policy. The government realized at the time that the country needed qualified persons in order to run its industries, thus it placed emphasis on good and quality education for its citizens Thus the government can be attributed as one of the biggest enablers of the export trade and economic development of the country. Policies regarding export trade were drafted and based on phases. For example, the plan applied all through the 3 decades can be divided into phases. Throughout the first and second financial year phases, the country was involved with export of any goods. There was a generalization on the types of goods to be exported. The 3rd and 4th year was characterized by exports of heavy industrial machines while the phase after 1980 was characterized by export of high tech machines. This led to a steady and strong growth in South Korea’s economy (Balassa, 570). Taiwan Of all the three countries discussed under the first wave, Taiwan was relatively at a relatively better position to advance its export trade as it had acquired an already established infrastructure from its Japanese colonizers. There was no shortage of skilled labor as Chinese immigrants from the mainland came in droves. Land and education polices had already been established and financial aid from America fuelled the development in the country. We will write a custom Essay on The economy of Asian countries specifically for you! Get your first paper with 15% OFF Learn More This enabled the country to concentrate on the development of firms that could export products of international standards. Government policies are also largely responsible for the booming export trade as they allowed the private sector to thrive and provide the needed momentum for economic growth. In addition, the Government has promoted a secure macroeconomic environment. It has also ensured strived to support local investments, industrial expansions that will drive up export volumes The similarity between all the three cases is that the Government is hugely responsible for establishing crucial policies that have led to the growth of export trade in the countries. Second Wave of Economic Revolution At a common point, it can be said that commerce and manufacturing guiding principles of the Economies that made up the 2nd wave i.e. China, Thailand and India, were similar to those of countries that made up the first wave. I.e. Japan, South Korea and Taiwan. After a phase where the countries implemented import substitution and where China’s policy was more focused on central planning, all the economic policies evolved to become more export oriented. This change in policies led to a further increase in trade (export and import) of goods. This had a net resultant effect of higher GDP growth (Chang, 136). Critics have argued that where economic growth of the “first wave” countries was largely attributed to abnormally positive global trade environment, countries involved in the second wave had to endure a more complex environment that was plagued by increased and selective trade protectionism among trade partners witnessed from the fifties and sixties. Despite of all the complexities, these economies have emerged as the leading lights of Asia’s economic growth. Another key difference between the two waves was that where export promotion was utilized by Japan, South Korea and Taiwan to encourage their local industries, countries in the second wave have not comprehensively utilized this tool and have instead used their exchange rate policies to stabilize their domestic macroeconomic environment rather than for export competitiveness. In the case of China, economic growth has been realized despite the inherent political risk that the country faces. China being a one party state faces a political risk for local and foreign businessmen and investors (Chang, 142). Not sure if you can write a paper on The economy of Asian countries by yourself? We can help you for only $16.05 $11/page Learn More Conclusion In summary from the above understanding of export policies in Asia, it is apparent that success that did not happen overnight due to supply and demand. Instead the economic boom was attributed to government intervention and participation in the development of local enterprise. Most notably, stages of booming growth and expansion were distinguished by public policies enabling a steady fiscal environment with a diverse range of incentives for the private sector. Incentives also included the promotion the addition of both human and physical resources. Works Cited Balassa, Ben (1964), “The Purchasing Power Parity Doctrine: A Reappraisal”, Journal of Political Economy, 1964. Vol. 72, 584-596. Buckley, Roy. (1998), Japan Today, Cambridge University Press, New York and Melbourne, 2007. Chang , Hinn.(1993), “The Political Economy of Industrial Policy in Korea”, Cambridge Journal of Economics, 2003. Vol. 17 (2), 131-157.

UM Water Pollution Global Crisis & Effects on The Environment Infographic Discussion

UM Water Pollution Global Crisis & Effects on The Environment Infographic Discussion.

Instructions (see associated point value for grading)1) Identify 3-6 scientific facts related to your topic(Water pollution that are likely to be influential with your target audience. (20 pts)2) Make note of the source and ensure it is credible3) Organize them in a logical flow that guides your audience in the
direction you want them to think – make reference to a call to action
(10 pts)4) Come up with a strong headline that supports your persuasive message (10 pts)5) Design visuals to explain the 3-6 of the scientific facts you
identified. Data may be presented in text too – make sure you have good
balance of “info” and “graphics” (20 pts)6) Use a style of language and design that will appeal to your target audience (10 pts)7) Include references citing the source of your data (10 pts)8) Submit accompanying explainer document that includes: (20 pts) a. Scientific facts being communicated through infographic b. Source(s) of data c. Intended persuasive goal and call to action d. Explanation of design elements intended to appeal to your audience (colors, icons, illustrations, text features)You will submit (a) an infographic graphic Note: It can be made on Canva, Illustrator, InDesign,
Excel, Word, a web based infographic tool. or anything else that makes
sense)(b). Explainer document
UM Water Pollution Global Crisis & Effects on The Environment Infographic Discussion

The Singapore Cultural Analysis Cultural Studies Essay

programming assignment help Singapore is a small island in southeast Asia Known for its trade and tourism. It is a small island with not much history but has a strong economy, stable government and a vibrant culture. II. Brief discussion of the country’s relevant history Singapore was a British colony for nearly 150 years merged with the Malay territory. In 1965 it gained independence from the British and was separated from Malaysia to from a new country called Singapore the name derived from singa-pura which means city of the lion. . (, n.d) III. Geographical setting Situated in Southeast Asia, Singapore is a small island with a total area 647.5 square kilometers, with land being 637.5 and water 10 square kilometers including the main island and around 60 islets and the coastline extends to 193 kilometers. Malaysia, Indonesia and Brunei are the bordering countries to Singapore. It is the focal point in the Southeast Asian sea routes. A.Location Singapore is located at the tip of the Malay Peninsula in Southeast Asia in between Malaysia and Indonesia. 1 22 N, 103 48E is the geographical location of Singapore. B.Climate Singapore experiences tropical climate with high humidity and rainfall. There are no specific rainy and dry seasons but during the northeast monsoon (dec-mar) it receives abundant rainfall and during the southwestern monsoon (jun-sep) it is the driest comparatively. C.Topography Singapore Island is mostly low-lying, green, undulating country with a small range of hills at the center. The highest point is Bukit Timah which is 166 meters and the lowest point is the Singapore strait which is 0 meters. There are sections of rainforest in the center and large mangrove swamps along the coast, which has many inlets, particularly in the north and west. Singapore’s harbor is wide, deep, and well protected(Singapore overview , 2007). IV. Social institutions A.Family 1.The nuclear family The general family trend in Singapore is a nuclear family which is the parents and the unmarried children living under the same roof. About 85% of Singaporean families are nuclear families. . (, n.d) 2.The extended family Close links are maintained between the relatives from both the mothers and fathers side. There is a positive amount of interaction between the extended family with them getting together during festivals and celebrations. . (, n.d) 3.Dynamics of the family a. Parental roles The parental roles that is the duties and responsibilities of a parent towards their children are shared equally by the mother and the father. b. Marriage and courtship Monogamy or having only one wife is the general rule in Singapore but Polygamy or having more than one wife at the same time is allowed among Muslim Malay. The divorce rate in Singapore is seemingly increasing but Interethnic marriages still are had to come by. The average age at first marriage has increased, and it is customary for young people to live with their parents until they marry. . (, n.d) 4.Female/male roles (changing or static?) The male and female roles are changing with 80% male employment and 50% female employment. Women are being given more importance in society through the time but there still lacks female involvement in the managerial or high level roles. (, n.d) B.Education Singapore has a very high literacy rate with a strong education system. The education system is based on six years of primary school, four years of secondary school and later vocational school or university, depending on the grades and student prefferences. The best schools are very demanding with the competition being high and fierce. (, n.d).Singapore one of the most prominent education hubs in Asia with high levels of education standards attracting students from all over the world with some of the best universities and institutions in the world. 1.The role of education in society Education plays a very prominent role in society were children are thought to hold the key not only to their own future but also to the future of their families. The average age at which children start school is six. (, n.d). Due to the increasing competition for jobs and personal improvement in Singapore there is high emphasis given to good education and nurturing and promoting the various talents of the students. a. Primary education Primary education is a total of six years which consists of a four year foundation stage from Primary 1 to 4 and a two year orientation stage from Primary 5 to 6. The overall aim of primary education is to give students a good grasp of English language, Mother Tongue and Mathematics. There is no fee for primary school but there are some miscellaneous expenses which add up to SGD $11/ month. During primary school the students are encouraged to participate in Co-Curricular Activities and Community Involvement Programs to develop early skills. At the end of primary school the students have to take a national level examination called the Primary school leaving examination (Ministry of education, 2012). b. Secondary education Secondary education consists of four to five years of school in which the students are placed in Special, Express, Normal (Academic) or Normal (Technical) course according to how they perform at the Primary school leaving examination. The different curricular emphases are designed to match their learning abilities and interests. The fees for secondary school varies from $5/ month for public schools, $3-$18 for autonomous schools and $200-$300 for independent schools. For graduating from secondary school the students have to attend a national examination called GCE ‘O’ Levels(for Special/Express courses) or GCE ‘N’ Levels (for Normal course).All students take part in at least one Co-curricular activity; CCA performance is considered for admission to JCs, CI, polytechnics and ITE(Ministry of education, 2012) c. Higher education Singapore has some of the best universities offering various programs. The National University of Singapore, Nanyang Technological University, Singapore Management University and Singapore University of Technology and Design are some of the most reputed universities in Singapore. These universities have a worldwide reach and attract thousands of students each year. There are universities from all over the world also who offer their programs in Singapore either by collaborating with Singaporean institutions like university of Whales and university of Bradford who offer their programs through Management Development Institute of Singapore (MDIS) or by setting up a sister campus in Singapore like INSED which is one of the world’s premier business school from France and James Cook university an Australian university have sister campuses in Singapore. 2. Literacy rates Singapore has a high literacy rate due to the emphasis given to education. The % of people above the age of 15 who can read and write is total population: 92.5% male: 96.6% female: 88.6% (2000 census) (Singapore-counrty profile ,2012) C. Political system Singapore is a republic with a parliamentary system. As a former British colony, Singapore since independence in 1965 has adopted the Westminster Module. The head of state is the president, who is elected for a fixed term of six years. The parliament is elected in a general compulsory election every five years. There are also six nominated members of the parliament. The cabinet is the executive organ of the state, and execution of government policies is carried out by ministries and statutory boards. . (, n.d) 1.Political structure: Singapores government is segrigated into three segments. -Executive- This includes the presedent who is the head-of-state abd the cabinet which is lead by the prime minister.( , 2011) -Legislative- The Legislative branch is the Parliament, which is elected by general election every five years. The first sitting of Parliament was held on 8 December 1965. The first general election for Parliament was held on 13 April 1968. There are 22 registered political parties. .( , 2001) -Judiciary- The Supreme Court and its Subordinate Courts make up the judiciary. The Judiciary administers the law independently of the Executive and this independence is safeguarded by the Constitution.( , 2011) 2.Political parties- There are 22 political parties in singapore and are as follows: Singapore Chinese Party Persatuan Melayu Singapura Partai Rakyat, Singapore State Division Angkatan Islam The Workers’ Party Pertubohan Kebangsaan Melayu Singapura People’s Action Party (PAP) United People’s Party Barisan Socialis (BS), Socialist Front (SF) Parti Kesatuan Ra’ayat (United Democratic Party) Singapore Indian Congress Alliance Party Singapura United National Front National Party of Singapore The People’s Front Justice Party, Singapore Democratic Progressive Party People’s Republican Party United People’s Front Singapore Democratic Party (SDP) National Solidarity Party (NSP) Singapore National Front. ( , 2007) 3.Stability of government The Singapore government is very stable. There has never been a political imbalance and the government has never been dissolved. 4.Special taxes 5.Role of local government Since singapore is such a small country it does not have divisions in local government and is ruled by divisions of the central government instead. In 1996 the then primeminister of singapore Goh introdused a system of community devolopment councils (CDC’s). In november 2001 the number of CDC’s redused from 9 to 5 consisting of South West, North West, Central Singapore, South East, and North East. They are managed by a council comprising a mayor and between 12 and 80 council members. ( , 2007) D. Legal system The legal system of Singapore is designed on the bases of British law. . ( , 2007) 1.Organization of the judiciary system. The judicial system consistes of the supreme court which is the higest level headed by the chief justice who is appointed by the president on the recommendation of the primeminister.It divided into the high court the Court of Appeal, and the Court of Criminal Appeal. This id followed by the subbordinate courts which are magistrates’ courts, trying civil and criminal offenses, the disrtict court, the juvenile courts, for offenders below the age of sixteen and the coroners’ courts; and the small claims courts, which hear civil and commercial claims for sums of less than S$10,000. . ( , 2007) 2.Code, common, socialist, or Islamic-law country? 3.Participation in patents, trademarks, and other conventions 4. Marketing Laws E. Social organizations 1.Group behavior 2.Social classes 3.Clubs, other organizations 4.Race, ethnicity, and subcultures Singapore is predominantly Chinese with 77% of the population being Chinese according to the 2002 census. It also mentioned that Malays consist of 14% of the population and Indians consist of 8% of the population. The rest 1.4% of the population consisted of various other ethnic groups.( , 2007) F.Business customs and practices V. Religion and aesthetics A.Religion and other belief systems There is freedom of religion with some exceptions. Singapore has been described as one of the most religious countries in the world. The major religions are Islam (Malay), Hinduism (Indians), Buddhism, Taoism, and folk religion (Chinese), along with a substantial number of Christians of various denominations. 1. Orthodox doctrines and structures There are many Chinese and Indian temples, Malay mosques, and Christian churches in the main public arenas for religious activities. Much religious activity is also carried out in the home. There are different “street festivals” according to the ritual calendars of the different ethnic groups. . (, n.d) 2. Relationship with the people Even with the vast difference in religious beliefs the people of Singapore live in peace with each other maintaining good relationships with people from all religious backgrounds. 3. Which religions are prominent? The Chinese religions of Buddhism, Taoism, and Confucianism are the most prominent with 51% 4. Membership of each religion The Chinese with Buddhism, Taoism, and Confucianism take up most of the population with 51%. About 15% of the population is Islamic About 15% of the population is Hindu And the rest of the population are from various other religions such as Christianity, Jewish, Jain and Sikh ( , 2007) B.Aesthetics 1.Visual arts (fine arts, plastics, graphics, public art, colors, etc.) 2.Drama, ballet, and other performing arts Today in Singapore people who go to theatres enjoy traditional ethnic theatre such as Chinese opera and Malay bangsawan (which took root in Singapore in the 19th and 20th century respectively), as well as contemporary theatre, which emerged in 1950s and 60s with the establishment of mainly amateur groups. English language theatre gained prominence from the 1980s with a change in educational policy which emphasised English to be the main language of instruction. Today with more than 130 theatre companies and societies in Singapore, practicing a range of contemporary and traditional ethnic theatrical forms Singapore has a vibrant performing arts developed through time..(National Arts Council, 2012) 3. Folklore and relevant symbols Singapore like most Asian countries hos a rich folklore and legends from which symbols are dericed. One such folklore about the symbol of Singapore which is the merlion explains that one day the villager in the southern cost were awakened by howling winds and crashing waves. It was covered with black clouds and was thought the whole island would be engulfed by the sea. The villagers went down on their knees in prayer and suddenly in the sea appeared a gigantic creature half lion and half fish and won the battle against nature and saved the villagers. (10 Legends and Myths of Singapore, 2012) VI. Living conditions Singapore has one of the best living conditions in the world attracting people from all over the world to live, work and study there. A.Diet and nutrition 1.Meat and vegetable consumption rates Singapore has high meat and vegitable consumption rates. With the variety if foods available in singapore the main components in every day meals are Rice, fish, chicken, and vegetables. 2.Typical meals There are 3 main meals breakfast lunch and dinner and Rice, fish, chicken, and vegetables are the staples. The main ingredients are mixed with spices, coconut, lime, chili etc create numerous varieties of dishes. Each ethnic culture has its own special dishes. (, n.d) 3.Malnutrition rates Singapore has a low malnutrition rate with childern below the age of 5 having only 2.2% malnutrition rate.( Health Statistics > Malnutrition prevalence, height for age > % of children under 5 (most recent) by country, n.d) 4.Foods available Due to the vast culture and ethnicity Singapore has a variety of dishes from Chinese cuisines, Indian cuisines, Malay cuisines and with the influence of western culture have a large variety of wesrten cuisines available. Singapore is the food hub of Asia and because of the availability of such vast cuisines is an attraction to people from all over the world. B.Housing A vast majority of population live in public housing which is publicly developed managed by the Housing and Development Board. About 80% of the population live in public housing which are like small town ship with schools, markets and health centers. The rest of the population live in privately developed houses and appartments which are slightly more expensive than public housing. (Housing in Singapore, n.d) 1.Types of housing available There is public housing which includes three-room, four-room, five-room and executive flats. A three-room flat has two bedrooms , which is about 1,000 sq ft. A four-room flat has three bedrooms which is about 1,200 sq ft of space. A five-room flat is about 1,400 sq ft. An Executive mansionette has three and they are relatively larger than any other public housing units- some even have double storey, with the rooms on the second level. The rest of the population live in private housing which include privately maintained apartments, condominiums and landed properties.(Housing in Singapore, n.d) 2.Do most people own or rent? 80% of the population live in public housing the most part of this own their own houses. 3.Do most people live in one-family dwellings or with other families? Most people do live in one- family dwellings and not with other families as 85% of the population believe in nuclear families. C.Clothing Singapore is the fasion capital of Asia and one of the mian attraction to sinsapore is the variety of clothing availablt there. It has clothing from the best designers from all over the world and orchad street in singapore is a 5 kilimeter streach of shopping on both sides. Singapore without saying goes hand in hand with fasion and shopping. 1.National dress Singapore because of its vast culture and ethnicity does not have a natioal dress but each culture has its own traditional dresses wich are- The Peranakan- who are the mixed race of chinese and malay- The Nyonya Kebaya is the traditional dress The chinese- Cheongsam is the traditional dress for the women. The Indians- Sari is the traditional dress for women and Dothi Kurtha is the traditional dress for men. The Malay- The Baju Kurungis the traditional dress for women and The Baju Melayu is the traditional dress for men. (Deliatoh, 2011) 2. Types of clothing worn at work The normal clothing worn to work consists of trousers, long-sleeved shirts and ties for men and blouses, skirts or trousers for women. Because of the weather being hot and humid jackets are usually not required. Although Singapore is a liberal country, women should make sure they do not wear clothes that are too revealing. (Communicaid, 2009) D.Recreation, sports, and other leisure activities Recreation and leasiure activities play an important role in the busy lives of Singaporeans. Different groups are interested in different activities such as sports, adventure and water sports as Singapore has beautiful beaches or even shopping, parties and gambling. 1.Types available and in demand There are various ways singaporieans spend their time away from busy sceduels. The most popular are Motor racing, football, swimming, paragliding, scoobadiving, boatimg, gambling, sailing, surfing, camping, trecking, cycling and horse racing. (Adventure and Rcreation in Singapore, n.d) 2.Percentage of income spent on such activities E. Social security In Singapore instead of of a national social security there is Central Provident Fund. The Central provident fund is a compulsory savings scheme that was introduced in 1955 to help cover the cost of living for Singapore residents upon retirement / termination of employment. (, n.d) Money that is saved in the Ordinary Account of the CPF can be used to help pay for home ownership, education and investment. The Special Account is meant for old age and contingency purposes and to purchase retirement-related financial products. A portion of the CPF known as Medisave can also be used to help pay for hospital treatment and for medical insurance (known as MediShield). (, n.d) Every Singaporean and Singaporean Permanent resident should contribute to the CPF. Foreigners who are on a Work Pass are not required to contribute to CPF. However, when a foreigner takes up permanent residency in Singapore, the foreigner will be expected to contribute to the CPF scheme. Both the employer and the employee contribute to this fund in varying proportions. (, n.d) F.Health care The Singapore healthcare system comprises public and private healthcare, complemented by rising standards of living, housing, education, medical services, safe water supply and sanitation, and preventive medicine.Over the years, Ministry Of Health has followed the principle of ensuring that good and affordable basic medical services are available to all Singaporeans. MOH has been continuously fine-tuning the health care system to ensure that Singapore has developed its healthcare system into one that has received praise and recognition both locally and internationally.(Ministry of Health, 2012) VII. Language Singapore with its variety of cultures is a multilingual country. Its national language is Malay. English is the administrative language and the medium of instructions in school and the students choose one of their mother tongues either Malay Tamil or Chinese. (, n.d) A.Official language(s) The official languages of Singapore are Malay, english, Tami and chinese(Manadarin) (, n.d) B.Spoken versus written languages C. Dialects [insert text here] IX. Sources of information (1999) Singapore geography, retrieved from -Ministry of education(2012) Singapore: education system. Retrieved from Culture of Singapore-Countries and Their Cultures retrieved from – (2007) Singapore overview, retrieved from – Singapore- Country Profine (2012) retrieved from – Who We Are , retrieved from – National arts council (2012) arts forms, retrieved from -10 Legends and Myths of Singapore (2012) retrieved from – Health Statistics > Malnutrition prevalence, height for age > % of children under 5 (most recent) by country (n.d) retrived from -Housing in Singapore (n.d) retrieved from -Deliatoh (2011) The Traditional costumes of Singapore retrieved from -Communicaid (2009) Doing business in Singapore retrieved from Business in Singapore.pdf (n.d) Adventure and Recreation in Singapore retrieved from Singapore-Social Security Retrieved from -Ministry of Health (2012) our health care system retrieved from

Oncolytic Virus Therapy for Cancer

Oncolytic Virus Therapy for Cancer. Abstract Interest of oncolytic virotherapy is mounting from over the past few decades for treating many kinds of malignancies. Despite oncolytic viruses attain many successes in cancer therapeutic era; they all have still challenges in their developments. The interaction between virulence factors of viruses, hosts’ immune defense system, microenvironments and tumour factors are the hazardous influences in their achievements of novelties. Currently, with the thanks of modern recombinant biotechnology, most of the oncolytic viruses are increasing their tumour selectivity and specificity. On the other hand, they reduce their efficacies on physiologically functioning cells. Furthermore, combinational therapies with traditional anti-cancer treatment regimes have also promising and relevance outcomes. In 2004, Chinese food and drug administration (FDA) approved first oncolytic virus in treatment of head and neck tumours. However, they have some still unsolved obstacles in proper cancer therapy. In my paper, the current issues and future prospects of the oncolytic viruses are highlighted how to use as therapeutic weapons. Keywords: Oncolytic viruses; Oncolytic virotherapy; Cancer gene therapies; recombinant 1. Introduction Cancer is one of the leading causes of death globally comprising 13% of all deaths (7.6 million deaths) in 2008. Although well established conventional therapies including surgery, radiotherapy and chemotherapy are existed, we still need new therapies and strategic plans. Local therapies such as surgery and radiotherapy have been limited in disseminated tumours. Likewise, chemotherapy has some intolerable adverse effects and sometimes, pre-existing chemo-sensitive tumours are resistance to chemotherapy after prolonged used. Thus, we really need certain promising therapies to handle these problems. Recent years, oncolytic virotherapy is uprising and promising for the various types of cancers. Ideology of virotherapy treating the malignancy has been introduced since early 20th century. However, since early oncolytic viruses were targeted not only tumour cells but also the normal cells, interest in the virotherapy was declined. Therefore, many trials related with such therapy were terminated during the following decades. Late 1990s, interest of virotherapy was re-active with the advance of modern biotechnology. Today, concern of the virotherapy is high and it has the potential promises as a reasonable cancer treatment by itself or conjunction with other conventional therapies such as surgery, radio and/ or chemotherapy (synergic effect). Advance technology allows the development of oncolytic viruses which only effective on dividing cancer cells but not attack the normal dividing cells. There are generally two types of oncolytic viruses namely non-engineered (naturally occouring) and engineered agents. Both types may destroy the malignant cells without harming the normal cells. Generally, oncolytic viruses only infect and preferentially replicate within the cancer cells followed by lyses these cells. In recent years, many therapeutic virus candidates are emerging and testing their oncolytic prosperities with preclinical and clinical trials. Among them, adenovirus H101 was the first virus approved by Chinese food and drug administration (FDA) in 2004 as the adjuvant oncolytic virotherapy combined with pre-existing conventional chemo- and radiotherapy in the head and neck cancers. 2. Type of oncolytic viruses Oncolytic viruses are principally divided into 4 types according to their mechanisms of action. There are intrinsically tumour selective viruses, virulent gene deleted viruses, promoter inserted viruses and pseudotyped viruses. Genetic modified oncolytic viruses are manipulated whether insertion of the transgenes or deletion of the virulence genes. Naturally occouring tumour selective viruses are the viruses that are not genetically modified, direct targeting on the malignant cells. For instance, New castle disease virus, Vesicular stomatitis virus, Poliovirus and Reovirus are intrinsically tumour selective. However, affectivity is less due to depend on the natural strength of their lytic properties. Virulent gene deleted oncolytic viruses are more popular because their selectivity on target tumours are more specific without infectivity to normal ones. For example, herpes simplex virus, adenovirus, measles virus and vaccinia virus can be modified by deletion of their virulence protein coding genes. In addition, inserting of foreign genetic elements such as promoter region boost tumor specificity and selectivity of oncolytic viruses. Thus, tumour cells allow the replication of these viruses because only tumour cells can activate the promoter region of them. For example, prostate specific antigen (PSA) promoter inserted adenovirus CG7870 applies in prostate cancer and promising results were came out. Pesudotyped oncolytic viruses are modified with ligands which target tumour selective cell surface receptors. Therefore, they solely have their infectivity on malignant cells. (E.g. adenovirus delta 24RGD). Moreover, these viruses may reduce toxicity and dose requirement. 3. Characteristic features of standard oncolytic virus Since viruses can infect not only the malignant cells but also the functioning cells, oncolytic virotherapy is the critical therapy. Hence, safety and efficacy of the virotherapy are considerable issue and still challenging for further improvement. Potential oncolytic viruses are needed to confirm or compare whether they have real ideal characters of oncolytic virus or not. Standard characters of the oncolytic virus stated that (1) they only replicate within tumour with high multiplication rate, not on normal cells (2) less or no infectivity and virulence than their wild types (3) genetically stable so that mutations and recombination with other viruses are minimized for manufacturing and safety issues. DNA virus is more stable than RNA virus (4) can inactivated anytime with antiviral drugs or other mechanisms (5) considerable mass production (commercially available) can be possible with good manufacturing practices. Therefore, for development of virotherapy, all oncolytic viruses should be fulfilled above criteria. Adenovirus and Herpes simplex virus (HSV) have high selectivity and specificity on tumour cells with massive replication rate of 1000 folds in 1st cycle. Besides, they are considerably stable whereas terminate anytime with their respective antiviral therapy (e.g. adenovirus is self-limiting and HSV is treated by acyclovir). 4. Tumour selective mechanism With the knowledge of the malignant cells’ molecular biology, oncolytic virotherapy can be created to attack the tumour cells selectively. Cancer cells undergo changes ranging from subtle point mutation to chromosomal instability. Inherent tumour selective viruses specifically attack the tumour cells by targeting the specific tumour promoting pathway of the malignant cells such as activated Ras and AKT pathway, defective interferon (IFN) pathway etc. RNA-activated protein kinase (PKR) pathway is a natural process that inhibits viral protein synthesis. Physiologically, interferon (IFN) secreted from infected cells phosphorylates the PKR which subsequent phosphorylates eIF-2α. Then, phosphorylated eIF-2α interfere the oncolytic viral protein synthesis that require for their virulence. In contrast, Ras mutation and defective IFN in malignant cells disturbs the PKR pathway and favours the oncolytic virus activity. For instance, herpes simplex virus (HSV) containing neurovirulence gene γ34.5 that binds with intracellular phosphatase and dephosphorylates eIF-2α allowing replication of HSV in both normal and tumour cells. However, deletion of this gene permits to replicate only in Ras mutated or interferon (IFN) defective cells. Controversially, recent finding suggested that γ34.5 deleted HSV can also replicate in PKR functional malignant cells. It is seen to be defects in PI-3 kinase pathway which favours translation of γ34.5 mutant HSV. Moreover, genetically modified adenovirus (dl331), VAI mutant strain, prefers to replicate only in tumour cells with Ras activation. Similarly, dl331 is also effective in Epstein-Barr virus (EBV) associated tumours such as nasopharyngeal malignancy because Epstein-Barr virus expresses viral associated RNAs (VA RNAs) that defect PKR pathway. Many cancer cells over-express receptors for virus in high level. Thus, exploiting this mechanism, many oncolytic viruses are selectively homed in their specific malignant cells. For example, over-expression of intracellular adhesion molecule 1 (ICAM-1) and decay acceleration factor (DAF) in tumour favours to infect Coxsackie virus A21. Besides, Newcastle disease virus (NDV) binds sialic acid receptors. Alpha virus similarly uses heparin sulphate or ICAM-1 as its receptors. Both of them are highly express in tumor population. Therefore, these viruses are highly concentrated in tumour cells. 5. Immunogenicity of virotherapy Likewise as many other viruses, oncolytic viruses also stimulate and activate the body defense mechanisms including innate as well as adopted immunity. These viruses produce the viral proteins required for their replication within tumour cells. These proteins also stimulate the MHC class I gene to present it on the cellular surface of tumour cells as well as on the normal cells. MHC class I antigen was recognized by cytotoxic T cells (CTLs) or CD8 cells which may destroy any cells representing MHC I antigens. Therefore, nature immunity allows eliminating both tumour and normal non-dividing cells. So, oncolytic viruses may also destroy normal cells apart from abnormal ones. An immune mechanism on the oncolytic viruses is one of the major constraints for developing modern virotherapy. However, to date, genetically modified viruses can only replicate and lyses p53 mutant cells. They cannot inactivate p53 gene of the normal host cells. p53 is functional and prevent replication of these viruses in the normal host cells. So, they are allowed their functions only in mutant tumour cells. 6. Conversion of oncogenic to oncolytic Many oncogenic viruses are potential to use as oncolytic therapy nowadays after genetically manipulation. Generally, 15-20% of the carcinogenesis is contributed by various kinds of oncogenic viruses such as herpes papilloma virus (HPV), Epstein-Barr virus etc. Reversely, these viruses can be changed to treat the malignancies by exploiting their lytic effects on the dividing cells. One of the classical examples is herpes simplex virus type 2 which is ongoing trials in many tumour cell lines by deleting its oncogenic genes coding thymidilase kinase or ribonucleotide reductase. Therefore, even tumourogenic agents can be used as oncolytic therapy by engineering their oncogenic gene components. 7. Novel oncolytic viruses 7.1. Adenovirus Adenovirus is interested in treatment of brain tumour especially in glioma multiforme. This tumour is never metastasized and contributed as single lesion. Moreover, it is almost resistance to systemic therapy because of blood-brain barrier and lack of cell mediated antigen drainage. However, fortunately, oncolytic viruses can replicate and spread within the tumour population since blood brain barrier create immune privileged site. In glioma cells, tumour suppressor gene (Rb) is inactivated and lack of expression. Taking this advantage, genetically modified adenoviruses are constructed by deletion of eight amino acids in Rb binding region of E1A protein. Therefore, they are unable to replicate in the normal cells because viruses cannot inactivate Rb gene of the functioning cells. But they can easily divide within the malignant cells owing to the lack of Rb protein. Additionally, adenoviruses induce autophagy in infected cells (malignant cells) through down-regulation of AKT/TOR pathway. Many genetically engineered adenoviruses are still on trials including in vitro and in vivo tests. ONYX-015 (dl1520) is a simple adenovirus lack of E1B 55K protein which do not replicate in the normal cells. So, they only express their functions in p53 mutant cells. In other word, their function does not work in p53 competent cells. Onyx-015 is a first oncolytic virus that has been approved by china FDA to treat the head and neck cancers especially refractory nasopharyngeal cancer combining with standard cisplatin based chemotherapy. Onyx-015 should be given intratumoural or peritumoural injection because of their side effects (e.g. flu-like syndrome). In addition, it showed 50% response rate observed in phase I and II clinical trials of pancreatic cancer. Recent studies found that Onyx-015 replication is not solely dependent on p53 function. Onyx-015 can replicate within some p53 competent cells whereas sometimes, cannot replicate even in mutant p53 cells. It may think to be reliable on E1B 55K independent nuclear late mRNA export of the tumour cells but not in functionally normal cells. Besides, other co-founding effects should be considered. For example, increasing the temperature (fever, hyperthermia or drugs) promotes replication of E1B deficient adenovirus in the malignant cells rather than normal ones. dl250 mutant strain is engineered by deletion of E1B 19K which is homologue of Bcl-2 and also inhibits pro-apoptotic protein Bax. Functionally, Bcl-2 is the anti-apoptosis protein. Hence, deletion of E1B 19K leads to permit cell death in Bcl-2 over-expressed tumour cells. It may also reduce expression of anti-apoptosis proteins and various growth factors. This type of virus is more potent in anti-tumour activity than dl1520. Delta 24 (dl922-947) adenoviruses are genetically modifying agents which are deleted the gene related with virulence factors and upregulate the transcription elements sensitive to the transcription factors of tumour cells. E.g. Delta-24 is modified by deleting of 24 nucleotides (pRb binding region) in E1A gene so that it is unable to inactivate Rb gene in the normal cells. So, it can only effective in the malignant cells. Now, many studies promise that it has potent anti-tumor effect in glioma. E1A mutants are more superior in oncolysis than E1B strains in vivo and vitro. Besides, Delta-24 RGD is more efficient in treating the low CAR (coxsackie-adenovirus receptor) expression malignant cells such as glioma and bronchogenic carcinoma cells. 7.2. Herpes Simplex virus First herpes simplex virus (dlsptk) as an oncolytic agent is developed in 1991 that is deleted in thymine kinase (TK) genes required for nucleic acid metabolism. Lacking of this gene, Herpes Simplex virus (HSV) lose its ability of replication in the normal cells. Hence, HSV only prefer to infect the tumour cells. HSV is a primarily potential treatment in several paediatric cancers including brain tumours. So far, γ34.5 deleted HSV are tracking on the clinical trials. These all vectors directly target to the tumour cells by deletion of neurovirulant gene γ34.5 (30kb) which is not essential for replication of the malignant cells. G47Δ HSV virus is derived from G207 parent virus. They are constructed by deletion of both copies of γ34.5 gene (1kb) and deletion of 312bp in ICP47 gene increasing oncolyitc efficacy. Also, they promote MHC class I expression in the tumour cells enhancing the immunogenicity of these cells. G207 variant was completed phase I study in glioblastoma multiforme resulting with no serious side-effects. Similarly, HSV 1716 is a genetically engineered variant by manipulating HSV1 stain 17 and deleting both copies of neurovirulent gene, γ34.5. Pilot study has already completed in Metastatic melanoma. NV 1020 (R7020) stain is the chimeric recombinant of HSV 1 and 2 with deleting one copy of γ34.5 gene, UL24 and 56 genes. Originally, it is developed as HSV vaccination. However, recently, it is still ongoing phase II trial on hepatic metastases of colorectal cancer by direct infusion into the hepatic artery. OncoVEXTM is recombinant vector with deletion of γ34.5 gene as well as ICP47. Deletion of γ34.5 reduces intrinsic neuro-pathogenecity of HSV whereas ICP47 deletion restores MHC class I presentation. Additionally, insertion of GM-CSF gene stimulates immune response of the host to the tumour cells. Releasing of GM-CSF promotes recruitment of dendritic cells for tumour specific response. It promotes tumour specific antigen (TSA) expression as well. Thus, OncoVEXTM affects not only on local tumour but on metastases or distant tumours. Currently, OncoVEXTM improved loco-regional control of head and neck cancers combining with chemo-radiotherapy. Intralesional injection of OncoVEX GM-CSF is ongoing phase I trials on cutaneous metastases and melanomas although it has dose related limitation such as injection site inflammation. Another advantage is that it is able to carry large transgenes up to 150kb. It is the main advantage of these viruses using for oncolytic agent although they may produce neurotoxity at high doses, difficult cloning and reactivate latent herpes infection which are hidden in the nervous systems (Ganglions). 7.3. Newcastle disease virus Newcastle disease virus (NDV) is paramyxovirus containing single stranded RNA which causes Newcastle disease in avian (birds). Earliest NDV (73-T strain) has been started to use as a clinical trial oncolytic virus for cervical cancer in 1965. Based on their oncolytic properties, NDV is divided into lytic and non-lytic stains. Lytic strains direct lyses the targeted cells. Currently, 2 lytic strains of NDV are ongoing trials which are NDV-HUJ and PV701. Both are naturally occouring live attenuated viruses. As NDV-HUJ strain is a neurotropic virus, it applies in glioblastoma multiforme (GBM). Likewise, NDV-PV701 strain has effect on many types of tumours. Results of their trials have potential promising. One of the advantages of NDV is that it selectively replicates in the tumour cells, not on normal ones. When NDV has also studied in breast cancer patients neoadjuvant with chemotherapy, outcome was desirable with minimal adverse effects including fever, flu-like syndrome, hypotension etc. Occourance and severity of side effects is reduced in subsequent therapy due to development of NDV antibodies in patients’ serum. On the other hand, non-lytic strains disturb the malignant cell metabolisms leading to allow regression of the tumours. Common non-lytic strains include Ulster stain. NDV damages the malignant cells by either direct lysis of the cells, induction of cytokine production (Interferon, Tumour necrotic factor) or enhance apoptosis including both intrinsic and extrinsic pathways. 72-T stain induces cytokine release while Ulster stain over-expresses the TRAIL receptors on tumour cells surface which may lead to apoptosis. 7.4. Mump virus and Simian virus Mump virus is the first paramyxovirus trying to treat in variety of human malignant cells. Vaccine strain 79 (S79) has potential promising oncolytic virus because S79 can only be infected to the cancer cells but not in normal ones. Studying in nude mice, mump virus demonstrated its tumour inhibition effect significantly. Simian virus is also a rubulavirus and among them, strain 5 can be genetically engineered as an oncolytic virus. This modified strain is able to attack several different cancer cell types significantly. 7.5. Vesicular stomatitis virus Vesicular stomatitis virus (VSV) is only rhabdovirus potentially using in cancer therapy. VSV is a single stranded RNA virus considering for oncolytic therapy. Developing of the recombinant VSV virus in 1995, the role of VSV is amounting in virotherapy. In recent studies, genetically modified replication competent VSV prolonged survival of hapatocellular carcinoma, breast cancer and malignant melanoma. Oncolytic properties of VSV is more effective in type I interferon (IFN) resistance malignant cells. Tumour cells are defect in interferon (IFN) signaling pathways but activated in Ras -ERK pathway. However, VSV can also impact on the normal cells especially in high doses. Thus, early (prophylactic) interferon therapy is required concomitant with VSV virotherapy because interferon appears to prevent the viral replication within the normal cells. Using the advantage of replication within the interferon defect cells, recombinant VSV deltaM51 which is defective in M (matrix) protein (point mutation) was constructed. Matrix protein is the regulator protein that increases replication and transcription of the virus but blocks the host cells anti-viral mechanism. Studies showed that VSV deltaM51 strain has beneficial role in glioma cells xenografted nude mice. Furthermore, VSV shutdown the blood supply to the tumour leading to deprivation of oxygen and nutrients which may require for tumour growth. 7.6. Measles Measles as oncolytic therapy is more interesting since there was significant regression of Hodgkin’s lymphoma after infecting with measles virus. Resent study suggested that recombinant measles virus (Edmonston B strain) showed significant inhibition on xenograft SCID mice with human lymphoma cells. Next, Edmonston B stain specifically attracts CD 46 cell surface receptors that are highly expressed in human mesothelioma cells. Thus, this strain has highly attractive role in treatment of mesothelioma. In addition, engineered measles virus with interferon (IFN) β gene inhibits tumour angiogenesis rather than parental strain. Despite most of the people previously encountered with measles infection or vaccination in their early life which may cause therapeutic failure, the evidence highlighted that replication of measles virus was taken place even in the immune individuals. It seems to be immunosuppression due to cancer itself or concurrent use of other anti-cancer therapies such as radiotherapy, and (or) chemotherapy. 7.7. Poxvirus Vaccinia virus (VV) is the most potential candidate poxvirus utilized as virotherapy recently. This virus is genetically engineered by deletion of thymidine kinase genes like herpes simplex virus (HSV). For instance, JX-594 strain which is transfected with GM-CSF gene, displayed oncolytic activity in animal models. However, it may rarely affective in the normal cells. Most Vaccinia viruses kill the targeted malignant cells by apoptosis as well as traditional mechanisms. Myxoma virus, another poxvirus, is significantly effective on human glioma cancer cell lines. In addition, rapamycin (immunosuppressant) reinforced its oncolytic efficacy when using combination. 7.8. Togaviruses Togaviruses (Sindbis and Semliki Forest Virus) also show their potential roles in the oncolytic therapy. Sindbis virus (SIN) is an RNA virus that naturally infects human by mosquito bites. This virus binds with its receptors of 65kD (Laminin receptors) which are highly express on the tumor cells (tumour homing property). To take the advantage, Sindbis virus promotes considerably regression of the several tumor cell lines in vitro testing and xenograft SCID mice. In human study, it has promising effect on cervical and ovarian malignancies with minimal or no remarkable adverse effect on normal cells. Next, Semliki Forest Virus (SFV) may inoculate repeatedly without prominent immune response. Togaviruses favour as the oncolytic virotherapy agents due to their high replication rate, broad spectrum of host ranges, increase transgene expression and stable in blood stream. Apart from these viruses, Venezuelan equine encephalitis virus (VEE) is also a replication competent virus which is interesting in certain circumstance of oncolytic therapy. 7.9. Retrovirus Gamma retrovirus (moloney murine leukemia virus (MoMLV)) may have effect on the tumour cells not in the non-dividing cells. So, it may safe as oncolysis. For instance, when U87 glioma xenografted nude mice were administrated with MoMLV, significant oncolytic result has been reported. These viruses are less effect on normal cells due to lack of nuclear transport of viral genome. Certainly, they cannot replicate well within non-dividing cells. In addition, modified MoMLV viruses expressing HSV thymidine kinase (TK) have synergistic effect on glioblastoma cells combining with ganciclovir (anti-viral agent for HSV). Another retrovirus such as fomy virus has also intrinsic oncolytic property. It is researched recently on glioma implanted nude mice. However, the result is still controversial. Oncolytic Virus Therapy for Cancer

How good is your sense of observation?

How good is your sense of observation?.

Choose a spot that interests you. A space that might be inspiring to you or attracts you for
whatever reasons. (Landscapes are discouraged – try instead to choose something more
personal or an enclosed setting.) Then try to narrow your point of view down to one that
would be closer to a film/video frame. Stay there for some time and observe. Then, from
your vantage point DESCRIBE in great details what is going on in this “view.” Remember
that it takes imagination to observe. Do not limit yourself to the most obvious things but
spend a little more time to explore what they really are. Pay attention to textures and
light as we often overlook how they actually affect ways in which objects appear to your
eyes. You can eventually include in your description some of what is going through your
mind while being there. You can also think about how what you see affects you or is
connected to you. Conclude by telling us what you feel from the experience. AIM OF PROJECT: 1. Learning to pay attention to details: peculiarity of situations, motion, texture, shapes
and color. Also nature of materials, mood. 2. Learning to access how your own state of mind colors the way you see things:
memories, cultural background, habits, inclination. 3. Learning to differentiate between different levels of reality or perspectives. The
difference between you and what you observe. What is the meaning of “objective”
and “subjective.”
How good is your sense of observation?

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