Essay on America’s Role in the Cold War - 903 Words

America’s role in the Cold War After World War II, the United States had effectively become the most powerful and influential country in the world both militarily and politically. During America’s rise to power, however, hostilities mounted between America and the Soviet Union, resulting in a fierce rivalry. The Cold War, which never involved direct military confrontations between the two nations, involved of the struggle to contain the spread of communism, extreme anti-communist attitudes in America, and a reemergence of the civil rights issue. During the war against Germany, America tended to neglect the military desires of the Soviet Union. Roosevelt hesitated to open a second front against the Nazis and this hesitation saved many†¦show more content†¦Chinese involvement in the war, which lasted another two years, resulted in a stalemate. After Truman, President Eisenhower devised his own foreign policy. His â€Å"New Look† involved using massive nuclear arsenal for military leverage, ma nipulating Third World countries with CIA, and doing everything possible to contain the spread of communism. After World War II, President Truman lifted the controls on prices, causing drastic inflation and prompting workers to demand higher wages. He put several mining and railroad companies under federal control, sparking hostility from the Democratic Party. To jumpstart economic growth, Truman began enacting what he called the Fair Deal. This expansion of the New Deal addressed civil rights in addition to economic concerns. Due to opposition from Congress, only some parts of Truman’s Fair Deal were passed: an increase in the minimum wage, an increase in the scope of social security, and the enactment of the National Housing Act of 1949, which called for the construction of hundreds of thousands of low-budget housing units. In the midst of the political and economic discord, tensions were rising in America over the spread of communism at home. This sparked the creation of the House of Un-American Activities Committee, whose duty was to investigate communist influence in labor unions and New Deal organizations. During the â€Å"Great Fear,† allShow MoreRelatedAmerican Anticommunism During the Cold War Essay926 Words   |  4 Pages Subsequent to the conclusion of the treacherous Second World War, America prepared itself for a period of peace. This peacetime was short-lived, as America’s tolerance for communism receded this issue became the forefront for American concern. The United States of America, also referred to as the USA or US, regarded communism as a strategic threat due to its hostility to private property and free markets, policies that many Americans associate directly to political Read MoreThe Asian African Conference Of 19551250 Words   |  5 Pageswas Latin America’s role in the Third World Project? If Bandung was about Afro-Asian Solidarity, then when did Latin America emerge into the Third World? The history of the Third World can encompass many narratives. Using three distinct iterations of the Third-World movement from 1955-1966, this dissertation will shed light on multiple visions of Latin America and its place both within and outside of the Third World. In so doing it will attempt to understand what Latin America s role in the projectRead MoreEssay The Power of Ideology1484 Words   |  6 Pagesideologies, there would be no call to use such a disparaging weapon. The ideas of influential leaders, both right and wrong, are more potent in war than what is universally understood. The world in actuality is ruled by them, and contrasting ideologies cause massive collateral damage. Conflicting ideologies of Communism and Capitalism were set aside in World War II when the Russians and the Americans united as allies to face Nazi Germany as the common enemy. With the defeat of Germany, Russia and theRead MoreThe Politics Of Power By Ira Katznelson1315 Words   |  6 Pageseven ts leading to America’s great level of dominance. Throughout the chapter, a few key points were made. The main three points that were observed in this chapter consisted of America’s influence and global expansion, the transition into the globalization era, and environmental problems. From the beginning of the exploration era, to the globalization ear, foreign policy never escaped existence. The use of foreign policy continued into the beginning of World War II, after the war, and through presentRead MoreAmerican History and World War II Essay1393 Words   |  6 PagesOn December 7, 1941, with Japanese attack on Perl Harbor, all debate over avoiding war and the policy of American isolationism was gone. It was the beginning of a great war that brought death, devastation and finally the victory and power to United States. At the time of Roosevelt’s appointment in 1933, historically crucial events were taking place in Japan, Italy and Germany which had to shape th e future and the fate of United States. This paper studies and analyses the major factors which contributedRead MoreEssay on The Rise of the American Empire1639 Words   |  7 Pagesgaining independence in the years following the war. Britain’s stage left exit from its hegemonic role resulted in the start of a new â€Å"Great Game† between two burgeoning superpowers. A new world order began to take shape with the United States and USSR vying to establish their own hegemony. Aside from causing a major shift in geopolitical power, WWII also solidified the integral role oil played politically in national security. However, following the war the United States was no longer the world’sRead MoreFall Of American Power1504 Words   |  7 PagesFollowing the Cold War, and the collapse of America’s economic rivals from the time, the implosion of the Soviet Union and Japan’s economic deflation in the early 1990’s, the United States held important roles in international politics that went beyond its extensive military arsenal and nuclear capacities. The U.S., which was then considered an incomparable and unattainable power, sat on top of an influential global economy power capable of stimulating other nations to want to follow on its pathRead MoreThe Truman Doctrine1364 Words   |  6 PagesDoctrine and the Development of American Foreign Policy during the Cold War On March 12, 1947, President Harry S. Truman defined United States foreign policy in the context of its new role as a world superpower. Many historians consider his speech to Congress as the words that officially started the Cold War. The Truman Doctrine was a major break from U.S. historical trends of isolationist foreign policy. His speech led to the Cold War policy of containment. Moreover, it served as a precedent for futureRead More America’s Foreign Policy and the Cold War Essay1187 Words   |  5 PagesAmerica’s Foreign Policy and the Cold War The role of America at the end of World War II was where the origins of policing the world originate. America had been engaged in a very costly war in terms of dollars as well as lives. But, despite the expense the United States came out of World War II better than any other nation that was involved. The Second World War was a battle between the Allied and Axis Powers. The Allied Powers consisted of the United States, Great Britain, the Soviet UnionRead MoreEssay about Detente and the Cold War1017 Words   |  5 Pagessuper power following World War II. Many of the Allies were deeply affected by the war financially and were struggling, thus leaving a vacuum that needed to be filled. The United States was thrust into the position of â€Å"policing† and assisting nations around the world. The Cold War was in many ways a psychological illusion however there were many factors that led to this illusion which were well founded. The Cold War stemmed from a multitude of factors, the difficult war against Nazi’s and Japan

Air Pollution Is A Single Largest Environmental Health Risk

Air pollution is the presence in or introduction into the air of a substance in which has harmful or poisonous effects are being exposed into our atmosphere. Air pollution has been ranked as the largest health risk according to The World Health Organization (WHO). This World Health Organization reported that seven million people died in 2012 from air pollution-related sicknesses. From this statistic, this has led us to the proposal that air pollution is a single largest environmental health risk. This type of exposure has related itself to a large number of different adverse health effects that are most commonly heard of every day. Some of these health effects are associated with diseases such as COPD, asthma, other respiratory diseases,†¦show more content†¦These have all contributed to why and how our health effects from air pollutants are still problematic today. Our lives are impacted by what we do as humans living in this environment. There are many ways we can reduce t he rate of air pollutant diseases just by changing little things throughout our household and around our environment. The main reason why I wanted to write about air pollution was because of the massive issues that have occurred over the past years and have led up to our current health today. I was interested in informing myself more about the topic and how it affects us every day and what we can possibly do to help increase the quality of our air. Our environment is very sensitive and I feel that we should start being more observant on what we are doing that can make a change in our public and viral health. A lot of us take our environment for granted and I imply on changing peoples’ perspective so that we can all understand the standards of our environment and how we can improve it as well. While including many studies that can help us understand how our air quality is important, what causes the air pollution to make an impact, what kind of pollutants are harmful, and what are some main sources of air pollution. Two important sources of urbanization air pollution are traffic and power gener ations that can result in asthma. Asthma has two characteristics,

Clinical Experience Reflective Free Essays

Due Date: Week 13 Final Reflection: Final Reflection As another semester comes to an end, it is a good time to reflect on your experiences and your learning. To summarize your experiences in this course, we would like you to write up a 5-10 page paper about your experiences in this class. It should address three main areas: 1. We will write a custom essay sample on Clinical Experience Reflective or any similar topic only for you Order Now Your newly acquired knowledge of practical nursing. Think back to when you started this course; think about what you knew about practical nursing. Describe what you learned and what you would still like to learn. This section should describe how your ideas about 1 or 2 topics changed as a result of taking this course. Were they topics you misunderstood previously that you feel you understand better now? Were they topics that you felt were not relevant to your life that you are glad you learned more about? How has learning about these topics affected your thinking about practical nursing or interprofessional practice in general? 2. Newly acquired knowledge about you as a learner. This section should describe your experiences as a student in this course. What did you do well as a student in this course and what did not go quite as well as you expected? What advice will you give yourself as you take on other courses? 136 George Brown College Practical Nursing COURSE NAME: Practical Nursing Clinical Applications I COURSE CODE: NURS 1029 3. Personal reflection. This section should address your personal experiences in the course. What did you learn about yourself as a person? If you could look at yourself through the eyes of your professor, what would you want your professor to know about your growth as a person, a student and a student practical nurse over the course of the semester? Describe one challenge you faced in this course and how you handled it (did you overcome it? How? If not, why not? ) Process: 1. Using 3 resources/ professional journals linked to practical nursing or interprofessional practice, you are to write a reflective essay on your role as a member of the interprofessional team, practical nursing, turning theory into practice. 2. The essay’s length is not to exceed a minimum five pages and maximum ten pages, presented professionally in 12 font Times New |Roman, double spacing using correct spelling and syntax. 3. A Reference Page must be included in your essay, using the APA referencing method. Grade: 20% *based on grading rubric How to cite Clinical Experience Reflective, Papers

Business Ethics Utilitarian Theory

Question: Discuss the ethical theories that may be relevant to each decision that Elaine and Dennis have made this situation. Answer: In the context of this case study, the decisions made by Elaine and Dennis have a number of ethical and moral grounds. As mentioned by Dion (2012) the Utilitarian theory of ethics says that an action is good if its overall effect produce more happiness than unhappiness. The acceptance of the lone application of the American drug dealing firm or the applicants in Elaines bank would create more unhappiness at the end than the momentary gain for the companies. Hence, the decision of rejection of the deals and the lone can be identified as ethical under the Utilitarian approach. On the other hand, the explanation of the ethical egoism developed by Nicillo Mechivelli can be referred in this regard. As discussed by Wolbring (2012) this particular ethical theory says that the end justifies the means. Hence, the decision of rejecting the loan application of Electrode International and the Brazilian company can be identified as an ethical decision. The lone would have helped them in operating a business which would create an adverse economic and environmental end. On the other hand, the decision regarding the cigar importing company was typically directed by the deontological ethics of Immanuel Kant. This theory says that the peoples action needs to be guided by moral laws and that regulations are universal (Dion 2012). This theory creates the basis of national laws. Here, Elaine took the decision against the Canadian company operating in the importing business of cigars from Cuba only because it was against the gridlines of the US laws. References: Dion, M., 2012. Are ethical theories relevant for ethical leadership?. Leadership Organization Development Journal, 33(1), pp.4-24. Wolbring, G., 2012. Ethical theories and discourses through an ability expectations and ableism lens: The case of enhancement and global regulation. Asian Bioethics Review, 4(4), pp.293-309.

Roles of Job Testing

A Guide to Shanghainese

A Guide to Shanghainese Since Shanghai is in the Peoples Republic of China (PRC), the official language of the city is standard Mandarin Chinese, also known as  Putonghua. However, the traditional language of the Shanghai region is Shanghainese, which is a dialect of Wu Chinese which is not mutually intelligible with Mandarin Chinese. Shanghainese is spoken by about 14 million people. It has retained its cultural significance for the Shanghai region, despite the introduction of Mandarin Chinese as the official language in 1949. For many years, Shanghainese was banned from primary and secondary schools, with the result that many young residents of Shanghai do not speak the language. Recently, however, there has been a movement to protect the language and to reintroduce it into the education system. Shanghai Shanghai is the largest city in the PRC, with a population of more than 24 million people. It is a major cultural and financial center and an important port for container shipments. The Chinese characters for this city are ä ¸Å Ã¦ µ ·, which is pronounced ShnghÇŽi. The first character ä ¸Å  (shng) means on, and the second character æ µ · (hÇŽi) means ocean. The name ä ¸Å Ã¦ µ · (ShnghÇŽi) adequately describes the location of this city, since it is a port city on the mouth of the Yangtze River by the East China Sea. Mandarin vs Shanghainese Mandarin and Shanghainese are distinct languages which are mutually unintelligible. For example, there are 5 tones in Shanghainese versus only 4 tones in Mandarin. Voiced initials are used in Shanghainese, but not in Mandarin. Also, changing tones affects both words and phrases in Shanghainese, while it only affects words in Mandarin. Writing Chinese characters are used to write Shanghainese. The written language is one of the most important factors in unifying the various Chinese cultures, since it can be read by most Chinese, regardless of their spoken language or dialect. The primary exception to this is the split between traditional and simplified Chinese characters. Simplified Chinese characters were introduced by the PRC in the 1950s, and can differ greatly from the traditional Chinese characters still used in Taiwan, Hong Kong, Macau, and many overseas Chinese communities. Shanghai, as part of the PRC, uses simplified characters. Sometimes Chinese characters are used for their Mandarin sounds to write Shanghainese. This type of Shanghainese writing is seen on Internet blog posts and chat rooms as well as in some Shanghainese textbooks. Decline of Shanghainese From the early 1990s, the PRC banned Shanghainese from the education system, with the result that many of the young residents of Shanghai no longer speak the language fluently. Because the younger generation of Shanghai residents has been educated in Mandarin Chinese, the Shanghainese they speak is often mixed with Mandarin words and expressions. This type of Shanghainese is quite different from the language that older generations speak, which has created fears that real Shanghainese is a dying language. Modern Shanghainese In recent years, a movement has started to try to preserve the Shanghai language by promoting its cultural roots. The Shanghai government is sponsoring educational programs, and there is a movement to reintroduce Shanghainese language learning from kindergarten through to university. Interest in preserving Shanghainese is strong, and many young people, even though they speak a mixture of Mandarin and Shanghainese, see Shanghainese as a badge of distinction. Shanghai, as one of the most important cities of the PRC, has important cultural and financial ties with the rest of the world. The city is using those ties to promote Shanghai culture and the Shanghainese language.

Should the Arctic National Wildlife Refuge be open to oil drilling Research Paper

Should the Arctic National Wildlife Refuge be open to oil drilling - Research Paper Example Environmentalists and other interest groups however argue that allowing oil drilling in the region would endanger the wildlife in the region, disrupting their reproductive cycles, their communication, and their endangering their lives. Advocates for oil exploration in the region however insist that the impact of oil drilling in the region on the wildlife would be minimal at best. Opponents to the drilling are not convinced of such contention. Hence, much controversy in this issue is apparent. This paper shall explore this issue and establish a clear and comprehensive discussion on the topic. It shall draw its discussion based on information gathered from scholarly materials and compare it with newspaper and materials from the print media. The discussions in both types of sources shall be analyzed and assessed based on reliability and their applicability to this subject matter. These sources shall serve as both informal and formal scholarly sources for this issue, establishing clear s upport for the topic based on clearly defined and clearly identified arguments from well-supported write-ups. Side A: Oil drilling should not be allowed in the ANWR Scholarly articles are also polarized on the issue with studies discussing the environmental and others the economic aspect of the issue. In a study by Brown (2005), the author discussed the value of the wilderness which is protected by the ANWR. The author further argued the importance of maintaining the area as a wilderness – an area which must be unexplored and untrammeled by humans (Brown, 2005). These environmentalists are firm in expressing that allowing oil exploration in the ANWR would ruin its pristine condition because human activities would blemish the landscape. The US Congress has even acknowledged the fact that â€Å"beauty is in part the glory of seeing moose, caribou, and wolves living in natural habitat, untouched by civilization† (as cited by Brown, 2005). Various studies on environmental positions on the issue set forth that preservation is a priority over any other considerations, and that lands which have been set apart from human exploration must be preserved as such. Most Americans seem to agree with this stance because surveys throughout the years indicate that majority of them do not support drilling in the ANWR. A paper by Kaye (2005) also sets forth similar positions by environmentalists on the issue. This paper also discussed the importance of preserving the ANWR as a wildlife refuge. This study points out that the ANWR provides sanctuaries and benefits which cannot be seen in any other region in the world. They describe it as a place to exercise restraint. It therefore implies that human activities must be fiercely restrained and restricted in this area because it represents the power which people seem to have over the area – a power which must be held back and controlled to a certain extent (Kaye, 2005). In effect, these studies point out the impor tance of controlling human activities, allowing it to be carried out elsewhere, but to be avoided in this region which has for millions of years been allowed to flourish and to exist as an area untouched by human hands. Other scholarly articles discuss how government officials are clearly recognizing the need for the US to explore its domestic sources of oil, and therefore the need for the

Coca-Cola Internal Analysis and SWOT Analysis Essay

Coca-Cola Internal Analysis and SWOT Analysis - Essay Example Naturally this means that the organizations must develop their internal capabilities to the extent that they will be difficult for competitors to imitate or substitute. This paper conducts an internal analysis of the Coca-Cola Company in order to delineate those resources and capabilities from which it derives its strength as well as those competencies that it either lacks or poorly executes and as such are its major weaknesses that competitors could exploit. The paper begins with an evaluation of Coca-Cola’s tangible and intangible resources that lead to its strengths then uses the value-chain analysis to bring out and then analyze the company’s weaknesses. Analysis Resource and competency analysis According to Henry (2011) whereas the existence of resources is important, by themselves they do not confer any benefits to the organization. It is how efficiently these resources are configured that provides the organization with competencies that allow the organization t o achieve competitive advantage. ... company able to blend ingredients into the unique Coke formula X -Ability to continuously come up with new products and/or expand product lines -Managing the world’s largest beverage distribution system (Coca-Cola, 2012) also effective in franchising -Enterprise Value: US$ 173.46 billion (Yahoo! Finance, 2012) -Current Ratio above 1 from 2009 to 2011 (EBIT Financial, 2012). -Return on Equity, Operating margin and Net margins have been double digits since 2007 (EBIT Financial, 2012) Financial - Has the resources for R&D, market development, market expansion and so on. -Company’s efficient in turning its product to cash - Ability to consistently deliver profits reassures investors and other suppliers of financial capital -146,200 employees Human -Also has a strong diversity and inclusion policy that enriches its talent pool - Holds secret formula X Intellectual / technological -Own and market four of the world’s top five nonalcoholic sparkling beverage bran ds: Coca-Cola, Diet Coke, Fanta and Sprite. Intangibles -Intelligently exploited the mystery of Coke’s formula X for market positioning -Renown for superior advertising and other market promotion techniques From the table above three key strengths emerge. Firstly, Coca-Cola has a remarkable global presence. This enables the company to leverage its economies of scale to weaken the power of its suppliers as well as its customers. Also, this global presence implies that the company is able to balance its performance in slow economic regions with that from booming economic regions to sustain its profitability. Secondly, the company’s healthy financial position even during the global recession gives it a good credit rating. This means the company can easily raise additional capital for various strategic

Issues of Gender Essay Example | Topics and Well Written Essays - 1000 words

Issues of Gender - Essay Example However, there is a lack of assistance and confidence among the men. As stipulated by Russell Sander’s essay on power/gender roles, women help each other and do not want to undertake their duties without seeking the ideas of their colleagues. Additionally, Russell Sanders argues that women views men as selfish creatures, since they are not focused on sharing their joy and privileges with women. Women determination and strong desire to succeed are vital aspects that, according to Russell Sanders, contribute to their perception that men enjoy more privileges. For example, college women want to share the power that their fathers once had. Despite the focus of women on becoming successful, gender disparities deterred them to get higher position at working place (Connell 19). Russell Sanders argues that most of the top managers are men who are served by female secretaries and female nurses. Despite the wide range of household chores that women undertake, in the last decades high nu mber of cases that depicted women bullying was reported in many regions globally. In 2012, women have attained political, economic, social, as well as scientific progress that has made them to achieve equal status and equal rights. Political Progress One of the major aspects that have contributed to the success of women in the current political scene is the increment on the number of female legislators in various parliaments world wide. In this way, the issues that affect women are widely discussed, thus, reducing the brutality and discrimination that hindered their development in the last century. For example, in the Nordic region women form 42 per cent of the legislators in the lower house (Fenstermaker and West 57). Other regions that have increased women representation in the law making organs of the government include America, Europe and the OECD countries. One of the major implications of increased women representational quota according to IPU survey is that they act as parlia mentary propellers of gender equality and development. As a result, there is freedom as a key indicator that is used by contemporary economists to measure the development of a country. Similarly, increased women participation in debates has resulted in improvement of women rights as compared to the last centuries when women rights attracted insignificant notice. Economic Progress The extensive campaign to curb gender discrimination in the work places and the adoption of affirmative action in the developed and developing countries has resulted in the increase of the number of female employees. Globally, more than 800 million women are engaged in economic activities. Through engaging in small enterprises, manufacturing and agricultural services women have significantly enhanced the GDP of many countries. This has caused respect from men and support from government and financial institutions. Even though the lack of adequate skills and access to financial resources is a major challenge affecting women in the developing countries, international community, including the UN, has initiated many forums that seek to improve the accessibility of financial resources for women. Canada is one of the regions that has implemented economic strategies to assist women to be economically productive. Through Canada International Development Agency, women organizations, such as Pakistan Mukhtara Mau, have benefited from various training programs on human rights and women economic empowerment. The strategies adopted by USAID in training women are other significant aspects that have contributed to women economic progress. For example, USAID has initiated trainings that are focused at meeting gender based targets in countries, such as Bangladesh, Kenya and Peru.

Restorative Justice: Process and Outcomes

Restorative Justice: Process and Outcomes Should restorative justice be defined as a process or a set of outcomes? Restorative Justice rather than relying on judges to sentence offenders, places great emphasis on the importance of reparation and gives a role to the victim of the crime and the wider community. (Newburn, T 2013:768) When it comes to the debate of how restorative justice should be defined, either as a process or a set of outcomes it could be said that while they both have legitimacy, restorative justice can only be defined as one or the other. There is a great disagreement among critics on whether the emphasis should be placed on the outcome or the process. A definition of restorative justice that highlights the importance of both restorative processes and outcomes is, restorative justice is a theory of justice that emphasizes repairing the harm caused or revealed by criminal behaviour. It is best accomplished through cooperative processes that include all stakeholders. (Van Ness and Heetderks Strong, 2006:43) Marshall (1996:37) whos definition is most frequently quoted said that restorative justice is a process whereby parties with a stake in a particular offence come together to resolve collectively how to deal with the aftermath of the offence and its implications for the future. Within this definition 3 core elements of restorative justice are identified. Zehr (2003) stated that the first element is that harm must be healed, restorative justice views crime as harm done to people and communities. It seeks to repair the harm caused by offenders. The second being that violations create obligations, offenders must understand their wrongdoing and restorative justice wants offenders to accept responsibility for their actions. The third element being engagement or participation, relationships are the focus, it is the crime that violates these relationships and restorative justice needs to repair them. The main aim is to mend, restore and build. Dignan (2005, cited in Newburn 2013:771) suggests that Marshalls definition is of very little value for several different reasons, one being it characterises restorative justice as a particular type of process but fails to focus on outcomes, in doing so raises the possibility that undue attention will be paid to questions of equality and fairness. It also fails to consider outcomes by diverting attention away from those cases where restorative justice processes may be inappropriate but where its values and aims may still apply. the process based definition of restorative justice is at best incomplete, because it has nothing to say on the subject of restorative outcomes (Walgrave, 2002:174) this is because there is no direct involvement from the victim needed therefore there is nothing restorative it is just an outcome. Restorative outcomes may include, restitution, reparation and reintegration. It can be argued that a restorative process may not necessarily result in a restorative ou tcome. For example, within restorative conferencing where a direct victim is not present or participating, decisions on outcomes may be left to state regulators. Walgrave argues for an outcome-based definition of restorative justice for example as an option for doing justice in the aftermath of crime that focuses on repairing the harm and suffering caused by the crime rather than preserving an abstract legal order. (Newburn, 2013:772) The victim is seen to be a central stakeholder, who holds an important role in shaping both the process and outcomes of restorative justice. Victims want information about the processing and outcome of their cases, answers to their questions, empowerment and vindication. The process of restorative justice is to meet the needs of crime victims that are not being adequately met by the criminal justice system. Victims may feel ignored or neglected by the justice process. Victims need answers to questions they have about the offense, why has this happened to them? Victims often feel like control has been taken away from them by the offense. Involvement in their own case can be an important way to return a sense of empowerment to them. Restitution by offenders is often important to victims this may come in the form of an apology. (Zehr 2003:18-20). However there are potential dangers when it comes to the victim they may simply become a mere prop used in a process rather than being an empo wered participant. The community is another stakeholder that is considered to be vital to restorative justice. There is a risk of domination, authoritarianism and vigilantism. In N Ireland a restorative justice process was set up in order to stop paramilitary punishments that were being carried out. Braithwaite (1996 as cited in Newburn, 2013) said there are 3 levels at which it is possible to conceptualise the process of restoring community through restorative justice practices. At a micro level it involves those who are close to both the victim and the offender. At a meso level restorative justice helps to foster a sense of community within institutions such as schools, churches and so on. Lastly at a macro level it helps to focus attention on designing institutions of deliberate democracy. Communities need from justice, attention to their concerns as victims. Opportunities to build a sense of community and mutual accountability. Encouragement to take on their obligations for the welfare of their mem bers, including victims and offenders, and for the conditions that promote healthy communities. Community also want assurance of not to repeat the same and preventive actions. (Zehr, 2003:22) The offender is the third stakeholder that is consider to be of value in the restorative justice process. offenders need the opportunity to take responsibility for the harm caused by their behaviour towards victims. Offenders need to take away from the restorative justice process, accountability that addresses the resulting harms, encourages empathy and responsibility, and transforms shame. Encouragement to personal transformation, including healing for the harms that contributed to offending behaviour, opportunities for treatment for addictions and/or other problems, and enhancement of personal competencies. Also encouragement and support for integration into the community (Zehr, 2003:21). Restorative justice aims to help prevent the offender from reoffending again in the future. Being able to face their victims in a restorative justice process provides a chance to also develop empathy and remorse while also having input into the process. Offenders can complete this process threw co mmunity service or by issuing an apology to the victim. Crawford and Newburn (2003, cited in Newburn 2013) stated that in order for there to be a restorative process, stakeholders involved rely on four forms of restorative justice practice. These practices are victim-offender mediation, conferencing, sentencing circles and community boards. This group of practices has in common a process where the offender, victim and other members of the community meet together to consider the impact of a crime or harm on victims and communities and try to develop a plan to repair this harm that meets the needs of those affected. In Northern Ireland, diversionary youth conferences are used as a form of restorative justice. If the offender admits their guilt, then the Public Prosecution Service decides that there must be a conference involving the victim and the offender. Participation in conferences are voluntary. The offender is given the opportunity to discuss the offence and what he/she is prepared to do to repair the harm caused to the victim. The victim is given the opportunity to tell the offender of the impact the offence has had and what they feel should be done to repair the harm. This may for example include an apology or reparation to the victim or community. (Public Prosecution Service N.I. 2008). Youth Conferences provide an effective, fair, proportionate and restorative response to those offending which provides satisfactory outcomes for victims. The aims of a youth conference are about repairing relationships, making amends and to be able to reintegrate back into society. To conclude it could be argued that when it comes to defining restorative justice as a process or outcome it can cause disagreement amongst critics. Gavrielides (2007) stated that those who agree with a process-based definition, tend to limit the scope of restorative programmes to cases that are considered appropriate for a restorative justice intervention or to those in which both parties are willing to participate and abide by the ground rules. However, restorative programmes may appear in different shapes and forms. By adhering, therefore, to a definition that understands restorative justice as a process, we risk excluding the mostly restorative and partially restorative programmes. And this is only one of the limitations of this approach. On the other hand, those who agree with the definition of outcome-based definitions risk stretching the concept to include programmes for example community service, which although may in the end result with restorative outcomes, they might not b e carried out respecting central restorative rules.

Saving American Agriculture Essay -- Agriculture Agricultural Economic

Saving American Agriculture American agriculture has changed dramatically since the first days of mechanized equipment and large-scale crop production. â€Å"Many conceived of farming as a rewarding life . . . and a source of moral virtue† (Mariola, 2005). While presently, many view farming as purely economic in purpose. It has been stated that farming in America is decreasing more quickly than any other occupation. Yet, population increases steadily, making agriculture all the more essential. Many current issues are affecting agricultural progress in America; basic concerns over water, land, and climate only begin to describe the complex predicament. Economics, as well as public involvement and education are important tools, needed to save American agriculture. Water is the chief resource for agricultural production. One historical dilemma between farming and water occurs when misapplication of chemicals and nutrients leach into the ground water table, or run off to rivers and streams, polluting this vital resource. â€Å"Twenty-five years after the Clean Water Act (CWA) was passed . . . [it was reported] that nearly 40% of waters were too polluted for basic uses† (Secchi et al, 2005). Projects to rehabilitate and conserve water often prove complex and expensive. Comprehensive understanding of the opportunity costs involved in management projects is key to forming an efficient conservation strategy. Similarly, it will be imperative to transition out-dated agricultural attitudes and routines towards new sustainable practices. The greatest motivation for this shift may be in the form of government subsidies and rewards for progressive, sustainable water management practices on agricultural lands. Favorable climate is another key... ...3. Secchi, S., Gassman, P.W., Jha, M., Kurkalova, L., Feng, H.H., Campbell, T., & Kling, C. (2005). The cost of clean water: Assessing agricultural pollution reduction at the watershed scale. Center for Agricultural and Rural Development, Retrieved March 26, 2007, from http://www.card.iastate.edu Lamptey, B.L., Barron, E.J., & Pollard, D. (2005). Impacts of agriculture and urbanization on the climate of the northeastern United States. Global and Planetary Change. 49, 203-221. Cox, L.A. Jr., Popken, D.A., VanSickle, J.J., & Sahu, R. (2005). Optimal Tracking and Testing of U.S. and Canadian Herds for BSE: A Value-of-Information (VOI) Approach. Risk Analysis, 25, 827-839. Hwang, Y., Roe, B., & Teisl, M. (2005). An Empirical Analysis of United States Consumers' Concerns About Eight Food Production and Processing Technologies. AgBioForum. 8(1), 40-49.

Competitive Strategies for Wal-Mart

The emergence of Wal-Mart as a big box retailer has changed retail in the United States, according to a 2008 article on Wal-Mart and competition in AllBusiness. com. Big box retailers typically have stores exceeding 50,000 square feet. This type of store is standard, with large windowless single-story buildings. Several other big box retailers like Toys â€Å"R† Us, Best Buy, Target, Lowe's and Home Depot have created competition for Wal-Mart. However, Wal-Mart has stood out as the perennial merchandise big box retailer, according to the AllBusiness. om article. Because of its big box status, Wal-Mart has exceeded small retailers in profits. Annual revenues for 2004 were slightly over $288 billion. Revenues in 2006 exceeded $350 billion. Wal-Mart maintains its status as a big box retailer by seeking profits through a high volume of low-price items. Low-Cost Leadership Wal-Mart's slogan is â€Å"Spend Less. Live Better. † The giant retailer prides itself on providing customers with low-cost items that beat competitors. Wal-Mart reported a 3.6   percent increase in net income from cost cutting, according to an August 2010 Associated Press article. Also read MGMT-QUIZ about types of competitive strategies Customers are cautious about spending because of a slow economy, and Wal-Mart continues to be their low-cost option. Customers choose to shop at Super Wal-Mart centers for groceries, rather than the local grocery store because of discounted items. For example, Wal-Mart offers $1 ketchup bottles and $4 for a case of soda. The Associated Press article stated that Wal-Mart benefited during the recession as affluent shoppers were forced to downgrade to cheaper options.

14 Free Apps That Will Make You Incredibly Productive

14 Free Apps That Will Make You Incredibly Productive Doug Aamoth, writing for FastCompany, has done the hard work of sorting through the dozens of apps that promise to make your life easier to uncover the ones that actually can  make your life easier! Here’s our roundup of the top 14 apps to have at your fingertips to maximize productivity and minimize chaos! Emails and CommunicationsBoomerangThis easy-to-integrate app is essentially a snooze button for your email. You can dismiss an email from your inbox and set a time for it to return later, write a draft response at 1 am and schedule it to send right as you walk into the office, or set reminders to reply at a more reasonable hour. The free version gives you 10 email interactions a month.Burner  and MailDropThis one is so neat- it generates disposable phone numbers (or email accounts) that you can use whenever you need to make a number publicly available (without leaving your own precious digits visible for mass consumption. MailDrop is a no-frills temporary email address that disappears after 24 inactive hours; it’s great for Craigslist or promotional blasts.CordChances are if you have the Apple iOS, you’ve accidentally mashed that little microphone button and sent an audio snippet from the inside of your pocket. Cord helps you do that on purpose and with a group- you can send 12-second voice messages back and forth with ease.Group MeCreate and disband on-the-go private chat rooms when you need to chat with a group of people at once (and then make them stop flooding your text inbox with emoji conversations).VoxerThis converts your phone into a walkie-talkie without the strenuous button pushing or limited 30-foot radius for maintaining a connection. You can also leave voice messages in case they miss your rendezvous.Scheduling and MeetingsMeekanThis group scheduling app identifies available meeting times with just a list of participant emails, accommodates multiple time zones, and coordinates with existing calendars.PreziMany of my stud ents used Prezi instead of Powerpoint this summer- it made me feel old. Retain your youth and relevancy by learning how to use this cloud-based presentation tool! It lets you stream to remote attendees and post public presentations.ToolsCCleanerFor six months I had a defunct wireless client pop up whenever I booted up my Mac asking permission to run itself; I couldn’t seem to figure out where to uninstall it! CCleaner to the rescue! It will speed up your computer by deleting the flotsam and jetsam left behind in upgrades, file transfers, and browsing.CanvasI am a sucker for an easily customizable form app. From invoices to other frequently used workplace templates, Canvas lets you make and share them easily.PostfityIf your business or your personal brand relies heavily on social media (which†¦ it should), an app like Postfity may help you manage the myriad channels of posts and content you want to space out evenly. It has a scheduling tool and a linking functionality so you can share the same thing everywhere, or diversify your media presence.(PSA: don’t have Twitter and Instagram post verbatim to your Facebook. Schedule slightly different content for each feed. Your family, friends, and colleagues will appreciate it).OnavoMaybe you’re constantly going back and forth with how much data you think you’ll use versus how much you actually use. Onavo can help! It will not only help track usage, but will also compress files accordingly to save your data mileage for the cat gifs that really count.SyncSpaceWho doesn’t love a virtual whiteboard? It never gets old! It has everything but the marker fumes, lets you and your team collaborate on a shared visual document, then emails the changes around later.BreatherImagine AirBnb and ZipCar had a baby that let you hold meetings in it. Breather identifies available workspaces around cities like New York, San Francisco, Boston, Montreal, and Ottowa; your phone will unlock your insta-off ice for a half hour at a time so you can meet with clients, charge your phone, or just put your feet up before dashing off to the next appointment.BRB scheduling a Breather to present my latest Prezi- everybody check their Voxer messages!

Free Essays on Johann Pachelbel

Pachelbel’s Canon in D Major Composed by Johann Pachelbel Canon and Gigue in D for 3 violins and continuo Lucerne Festival of Strings/ Rudolf Baumgartner Johann Pachelbel was a German composer and organist. He was born September 3, 1653 in Nuremburg and also died there on March 1, 1706. While alive he studied music under the likes of Heinrich Schwemmer, G. C. Wecker, and Kaspar Prentz. In 1673 Pachelbel went to Vienna and became the deputy organist at St. Stephen's Cathedral. In 1677 he became the organist in Thuringen at the Eisenrach court, where he served for just slightly over a year. Eventually he became the organist at the Protestant Predigerkirche at Erfurt, where he established his reputation not only as an organist, but also as a composer, and teacher. Erfurt was, of course, the ancestral home of the Bach family, and there he met Ambrosius' eldest son, Johann Christoph. Pachelbel undertook the musical education of the young man who, not many years later, would teach his brother Johann Sebastian all he knew. Pachelbel started a family in Erfurt. After the early death of his first wife and their child to the plague, he r emarried and produced 7 children. His travels finally led him home where he was invited to succeed G. C. Wecker as the organist of St. Sebald, Nuremberg, after his former teacher's death in 1695. He obtained his release from Gotha that same year and remained at St. Sebald until his death at the premature age of 52 (Hoasm). Pachelbel’s music is said to have pioneered symbolism by using certain scales and chords to represent particular moods. He is highly regarded for his use of chorale variation. But Pachelbel's importance is, in fact, perhaps greater as a composer for the organ. His chorale preludes, based on hymn tunes, strongly influenced J.S. Bach. He was also the author of a great many motets, arias and Masses, and 13 Magnificats which feature solo singers and a choir as well ... Free Essays on Johann Pachelbel Free Essays on Johann Pachelbel Pachelbel’s Canon in D Major Composed by Johann Pachelbel Canon and Gigue in D for 3 violins and continuo Lucerne Festival of Strings/ Rudolf Baumgartner Johann Pachelbel was a German composer and organist. He was born September 3, 1653 in Nuremburg and also died there on March 1, 1706. While alive he studied music under the likes of Heinrich Schwemmer, G. C. Wecker, and Kaspar Prentz. In 1673 Pachelbel went to Vienna and became the deputy organist at St. Stephen's Cathedral. In 1677 he became the organist in Thuringen at the Eisenrach court, where he served for just slightly over a year. Eventually he became the organist at the Protestant Predigerkirche at Erfurt, where he established his reputation not only as an organist, but also as a composer, and teacher. Erfurt was, of course, the ancestral home of the Bach family, and there he met Ambrosius' eldest son, Johann Christoph. Pachelbel undertook the musical education of the young man who, not many years later, would teach his brother Johann Sebastian all he knew. Pachelbel started a family in Erfurt. After the early death of his first wife and their child to the plague, he r emarried and produced 7 children. His travels finally led him home where he was invited to succeed G. C. Wecker as the organist of St. Sebald, Nuremberg, after his former teacher's death in 1695. He obtained his release from Gotha that same year and remained at St. Sebald until his death at the premature age of 52 (Hoasm). Pachelbel’s music is said to have pioneered symbolism by using certain scales and chords to represent particular moods. He is highly regarded for his use of chorale variation. But Pachelbel's importance is, in fact, perhaps greater as a composer for the organ. His chorale preludes, based on hymn tunes, strongly influenced J.S. Bach. He was also the author of a great many motets, arias and Masses, and 13 Magnificats which feature solo singers and a choir as well ...

Organizational Design, Growth and Challenges Research Paper

Organizational Design, Growth and Challenges - Research Paper Example This is an acronym used to depict the Strengths, Weaknesses, Opportunities and Threats of an organization. The four components are separate yet integrated; in this regard, the best way to carry out SWOT analysis entails identifying the strengths and weaknesses of any organization prior to tackling the opportunities and strengths. This paper analyses the strengths, weaknesses, opportunities and threats of Wal-Mart Stores. Wal-Mart Stores Inc. is a renowned American multinational retailer corporation operating chains of large discount warehouse and departmental stores. It is currently the biggest private employer in the world with slightly over 2 Million employees. Wal-Mart was founded in 1962 by Sam Walton. It was incorporated in 1969 and began to publicly trade in the New York Stock Exchange in 1972. Wal-Mart’s headquarters is based in Bentonville, Arkansas, USA. It has eminently expanded over the years. Currently, Wal-Mart runs 8,416 stores located in 15 different countries. With the view of understanding the entire environment of Wal-Mart, it is important to critically analyze its strengths, weaknesses, opportunities and threats (Oldham, 1980). As evidenced by its incredible success, Wal-Mart has abundance of strength. For instance, Wal-Mart offers a wide variety of merchandise at very competitive prices. Due to their large purchases they receive exorbitant discounts from their suppliers, which is passed down to the customers. Strength of Wal-Mart is in fact that they manufacture their own brands and supply goods from local suppliers to retailers. Wal-Mart’s large size and high purchasing power is also strength on its own. It has an incredible team of executives who form its leadership. This has equipped Wal-Mart with a management of high caliber. The company spends its resources carefully with the aim of maximizing their margins (Burton, 2012). With regards to weaknesses, Wal-Mart, being a large multinational company, has a large pool of employ ees. Managing all these employees is never an easy task. It, therefore, poses a major challenge to Wal-Mart’s management. Quality of goods sold is another major concern. Owing to its low prices, customers sometimes question the quality of goods. Customer satisfaction is, therefore, not guaranteed. As with opportunities, Wal-Mart has been able to expand into other countries and has formed partnerships with other companies. However, there are still some markets that are yet to be reached by Wal-Mart. Another opportunity is that of taking over some overseas companies, such as ASDA in the United Kingdom. With the escalated trend of internet shopping, Wal-Mart has the opportunity to develop strategies that will enhance home delivery of goods whose orders are placed via the internet. Another opportunity is that of creating convenience stores. This could enable Wal-Mart to overcome local restrictions, as well as travel costs. The most prevalent threat facing Wal-Mart is competition. Local, as well as international competition, has posed a major threat to Wal-Mart. Wal-Mart has been vulnerable to attacks regarding ethical issues as well. In this purview, they have been accused in providing low pay and poor working conditions to its workers. Environmental issues also threaten Wal-Mart’s success. Company/Organization Name: Wal-Mart Stores STRENGTHS WEAKNESSES Large market share Discounts by suppliers Price leader Large variety of

One Hundred Years of Solitude Essay Example | Topics and Well Written Essays - 1250 words

One Hundred Years of Solitude - Essay Example Ideally, Marquez was brought up by her paternal grandparents in Aracataca, Colombia. His childhood tales talks about a big home that are filled with ghouls, discussions in secret code, and relatives who could prophesy their own deaths (Villad 40-50). Through reading this book One Hundred Years of Solitude, one observes many elements of Marquez’s childhood. Conversely, the perspective for the book is Marquez’s own personal reminiscence for childhood, for his grandparents, for a big house overflowing with ghouls and endless laughter. Also, the context of the book is Marquez’s political viewpoint and the brutal realism of growing up in a predominantly turbulent developing country. Colombia has a long and tragic socioeconomic history, in which Marquez acquired knowledge about politics and economics. Intermittent absentmindedness, particularly of the critical happenings that shape Macondo town remains a structural persistent right through the novel, apparent in recurr ence and circularity. This repetitive behavior traits and names of the Buendia offspring; the outwardly endless civil wars; the succeeding refuge of annihilated Aureliano in the bare practice of making little gold fish, melting down and remaking them; the stages of dissatisfaction, lack of accomplishment and tragic death that curses pedigree. This novel appears to be suggesting that the failure to learn from one’s blunders, the lack of historical awareness, becomes the primary curse called upon Macondo’s history and therefore a critical element in the series of dealings surrounding the killing of the banana workers (Browitt 16-33). The chronological burden of wars, economic distress, consecutive ethical failures and political betrayal, ultimately leads to devastation. One Hundred Years of Solitude chronicles historical facts from the inside. Garcia Marquez adeptly avoids the melodramatic style of former socialist realisms by placing the storyline focalization within th e community of Macondo. He ingeniously permits the Colombian bourgeoisie to conceal its profligacy through its own dealings. Garcia Marquez’s technique around classical realists is basically to locate the story-telling height of popular culture, focalizing dealings in the course of their understanding of the townspeople, who through their discerning memory re-live the past. Furthermore, Garcia Marquez does not â€Å"problematise† the language of illustration; his magical realism changes the entity of representation itself, permitting the magical and superstitious world of oral folk mores to stand for itself. This novel makes use of eminent uniqueness of the Latin American modernist tradition (Browitt 16-33). The first thing the reader notices when reading Marquez’s novel is the mere quantity of dealings it covers, therefore making it a daunting task to provide a brief synopsis of the plot. Even though the novel rests on an impossible to read manuscript given to a family by a strange gypsy, there are many tangents and twirls as we realize the events of the Buendia’s in their home town of Macondo. This seemingly makes the novel a tad too difficult to follow, with family disputes, civil war, incestuous relationships and industrialization, tossing the story-line into many numerous directions. The political wars and quarrels in the novel reflect the taut relationship between the liberals and the conservatives throughout Colombian History, where the exertion for

A factor that effect normal speech development Essay

A factor that effect normal speech development - Essay Example At 2 years of age, the child is able to utter 2- word phrases. By 3 years, the child is able to form sentences, uses plurals and past tense, can make sentences with 3 to 5 words and 90% of the talk is understood by strangers. At 4 years of age, the child can make sentences with 6 words, can converse and tell stories. At 5 years of age, the child can make sentences with 6- 8 words, can name 4 colors and can count ten pennies correctly (Schwartz, 1990; qtd. in Leung & Kao, 1999). Delay in the development of speech is a major concern to both parents and pediatricians. Speech delay can occur with or without delay in other milestones. A child is considered to have delay in the development of speech when the speech milestone attained is significantly lower than that which is normal for that age. It is important to identify, investigate and institute appropriate intervention in speech delay because; this can have significant impact on the social, academic, personal and vocational life of th e individual. There are many causes for delayed development of speech. The most common cause of speech delay is mental retardation. Infact, it accounts for more than 50% cases of speech delay (Leung & Kao, 1999). Most often, speech delay occurs due to inadequate stimulation of the child. An older dominating sibling may steal all the attention of the elders of the house. Various hereditary factors can affect speech development. Delayed speech in parents can result in delayed speech in the offspring also. Many genetic diseases which lead to global developmental delay or mental retardation can contribute to delayed speech. Exposure to many languages at a time or frequent changes in the childs environment can contribute to delayed speech. Chronic ear infections, effusions and impacted wax can lead to hearing debility and hence delayed speech. Intact hearing is vital to speech and language development in the first few years of life.

Ethical Decision Reflection Essay Example for Free

Ethical Decision Reflection Essay To let go of someone you dearly love is very painful to do. The pains cause by ending relationship is very unbearable. Some people may find their world tear apart when they realize that their relationship with their partner is not going well. I have had this relationship in the past that truly marks in my heart and in my mind. I do love this person very much despite of his weaknesses and flaws but many people around us do not like the idea of being us together. At first, I try not to give ear to their comments and opinions because of my love for my partner. But in a long run, I decide to call it quits because I find out that my partner is having an affair with other man; take note, it’s a â€Å"man. † It truly hurts me a lot because he exchanges me to a man! It is a big slap my on face. That is the first factor I consider when I break up with him. He is not trustworthy and faithful. I just strongly believe that a woman is meant to be with a man and a man is meant to be with a woman. Though I live in a liberated world but I cannot just take and stand with this kind of idea that is having an affair with same sex. When I break up with him, I feel so much freedom that I never been experiencing when we are still together. I don’t know why I feel that way, but that is how I really feel. I feel like a bird being imprison in a cage for a long time and has the chance to be released. When my friends especially my parents learn about it, they are very happy and relieve. They don’t just like my partner because they can smell something fishy on him. After the break, I feel such joy in my heart and feel more beautiful inside.

Vitamin D Impact on the Liver and Kidney

Vitamin D Impact on the Liver and Kidney Revised vitamin D copy Sources and forms of vitamin D Vitamin D, also termed calciferol, is a fat-soluble secosteroid compound that is an essential regulatory factor for calcium and phosphate metabolism in humans and animals. Its biological functions involve a physiological action in bone formation and mineralization, muscle contraction, nerve signal modulation and transmission as well as many cellular metabolic effects in various organs. There are two forms of vitamin D that are metabolically important; vitamin D2 or ergocalciferol and vitamin D3 or cholecalciferol. The nutritional sources of both forms are limited to certain types of foods that naturally contain vitamin D and therefore it is added to some foods as a supplement. 1.1.1- Exogenous (Diet) Both forms of vitamin D (D2 and D3) are exogenously obtained in low quantities from some types of food in the diet. Vitamin D2 is rare as it is produced from fungal and plant sources such as mushrooms and cereals, as a result of irradiation, by ultraviolet photons, of the plant sterol ergosterol. When these foods are ingested, ergocalciferol is absorbed into the blood. Vitamin D3 , on the other hand, is available in very low amounts from animal sources including oily fish such as salmon and mackerel; other sources include meat, liver, cheese, cod liver oil, eggs and fortified foods such as margarine and milk (Holick, 2006; Engelsen et al., 2005; Nowson et al., 2004). Farmed salmon, for example, contains only 25% of the vitamin D levels present in wild salmon, however, the amount of vitamin D in canned food may affected by modern processing methods (Chen et al., 2007). 1.1.2- Endogenous In humans the principal precursor of vitamin D3 is cholesterol which is obtained from the diet. Cholesterol is initially converted to 7-dehydrocholesterol, provitamin D3, through the action of enzymes termed the mucosal dehydrogenase complex, present in the small intestine. Provitamin D3, is then incorporated within chylomicrons and transported to the skin where temperature dependent photoisomerisation processing of 7-dehydrocholesterol takes place in epidermal cells resulting in the production of D3. Within the epidermal cells, vitamin D3 undergoes photocoversion to its isomers 5,6-transvitamin D3 and suprasterol, a process which relies on the amount of ultraviolet radiation absorbed; inadequate sunlight exposure compromises this process (Holick, 2003; Iqbal, 1994). Sunlight exposure is therefore a crucial element in the regulation and enhancement of endogenous cholecalciferol production (Dusso, et al., 2005; Iqbal, 1994; Reichel, et al., 1989; Smith, 1988). Once photoconversion is completed, cholecalciferol binds to Vitamin D Binding Protein (VDBP) and transported to the liver for further metabolic processing. Vitamin D metabolism Both forms of vitamin D (D2 and D3) undergo similar metabolic activation in the liver and kidney respectively to produce the physiologically active form 1,25-dihydroxyvitamin D3. 1.2.1- Skin The skin is characterized by two layers, the outer epidermal region, consisting of several strata, and the inner dermal layer. Skin exposure to UVB rays in sunlight, characterized by a wavelength of 290 nm to 315 nm, allows the initial steps of vitamin D synthesis to occur using the substrate 7-dehydrocholesterol (7-DHC) as illustrated in step 1 of Figure 1. UVB absorption by 7-DHC is thought to occur actively in the stratum basale and stratum spinosum regions of the epidermal layer. The substrate 7-DHC is an important intermediate of cholesteryl ester biosynthesis from squalene. During the reaction, 7-DHC forms procholecalciferol through B ring opening of the steroid structure. This transition state is relatively unstable and can further undergo photocatalyzed reactions to form lumisterol and tachysterol (Wolpowitz and Gilchrest, 2006). Lumisterol and tachysterol have been shown to prevent vitamin D reaching intoxicating levels and do not have any direct vitamin D effects (Bouillon et al., 1998). In addition to this protective mechanism, previtamin D poisoning is also prevented because this is an equilibrium reaction that allows cholecalciferol to revert back to 7-DHC (Webb, 2006). Cholecalciferol (previtamin D3) is produced upon double bond rearrangement of procholecalciferol and remains in the extracellular space where it becomes bound to the ubiquitous VDBP (Holick, 2005). Figure1. Sources and steps of vitamin D synthesis in the three major sites: skin, liver and kidney (Figure obtained from Wolpowitz and Gilchrest, 2006). 1.2.2- Liver Cholecalciferol that has been transported to the liver undergoes the first step of its bioactivation, the hydroxylation of carbon 25 (Dusso, et al., 2005) by two hepatic enzymes; the microsomal and mitochomdrial 25-hydroxylases (Deluca et al., 1990). In hepatic cellular microsomes and mitochondria, vitamin D3 is hydroxylated at carbon 25 and transformed to 25-hydroxyvitamin D3 by both 25-hydroxylase enzymes. This enzyme complex requires the presence of essential catalytic cofactors including nicotinamide adenine dinucleotide phosphate (NAPDH), flavin adenine dinucleotide (FAD), ferredoxin and molecular oxygen for this reaction to proceed (Sahota and Hosking, 1999; Ohyama et al., 1997; Kumar, 1990). Recently, large numbers of hepatic cytochrome P-450 enzymes exhibiting 25-hydroxylase action have been identified in vitamin D activation pathways; these enzymes include CYP27A1, CYP3A4, CYP2D25 and CYP2R1 (Dusso, et al., 2005; Cheng et al., 2003; Sawada et al., 2000). However, CYP2R1 is b elieved to be the principal enzyme in the hepatic pathway and the presence of a genetic mutation in its gene may compromise the outcome of this process; both CYP27A1 and CYP2D25 demonstrate high capacity and low affinity features, therefore, their activity is considered insignificant in this pathway (Dusso, et al., 2005; Cheng et al., 2003; Sawada et al., 2000). This metabolic step is inefficiently regulated, i.e. the levels of 25-hydroxy vitamin D are elevated as dietary intake of vitamin D increases. Consequently, over 95% of 25-hydroxyvitamin D in serum circulates as 25-hydroxyvitamin D3 which has a half-life of approximately three weeks, and is therefore used in the assessment of vitamin D status (Dusso, et al., 2005; Reichel et al., 1989). The metabolically inert 25-hydroxyvitamin D3 is then transported to the kidney for the second step of its bioactivation. 1.2.3- Kidney The second step of vitamin D3 bioactivation takes place at the proximal convoluted tubule of the kidney. Hydroxylation occurs at C-1 of 25-hydroxyvitamin D3 whereby the highly active 25-hydroxyvitamin D3 1-ÃŽ ±-hydroxylase (CYP27B1) incorporates a hydroxyl group to Carbon-1 of the first ring to form the biologically active metabolite 1,25-dihydroxyvitamin D3 (Holick,2006; Dusso, et al., 2005; Deluca et al, 1990; Reichel, et al., 1989). The high activity of 1-ÃŽ ±-hydroxylase (CYP27B1) present in kidney is not unique to this organ and can also be found in some other organs (Bouillon, 1998). The renal hydroxylation of 25-hydroxyvitamin D3 is the rate-limiting step in the production of 1,25-dihydroxyvitamin D3 and is well regulated. An alternative pathway of hydroxylation of 25-hydroxyvitamin D3 within renal mitochondria takes place at Carbon-24 to form 24,25-dihydroxyvitamin D3 which is metabolically inert. This process is catalyzed by renal 24-ÃŽ ±-hydroxylase in response to 1-ÃŽ ±-hy droxylase suppression. However, 24-ÃŽ ±-hydroxylase not only initiates the attachment of the hydroxyl group at Carbon-24 but also enhances the dehydrogenation of 24,25-dihydroxyvitamin D3 and hydroxylation at Carbon 23 and 26 (Sahota and Hosking, 1999; Bouillon, 1998; Reichel, et al., 1989). Renal hydroxylases require the presence of catalytic cofactors that enhance their synthetic activities during this process. Figure 2 shows the details of vitamin synthesis including the enzymes and cofactors required for each step. Figure2. Enzymes, cofactor and intermediates compounds of vitamin D metabolism (Bouillon et al. 1998) 1.2.4- Regulation of vitamin D metabolism Numbers of factors have been demonstrated to be important in the regulation of vitamin D metabolism; particularly significant its regulation through renal production. The factors involved in this regulation comprise parathyroid hormone (PTH), calcitonin, dietary calcium and phosphate, insulin and insulin-like growth factor and 1,25-dihydroxyvitamin D3 itself (Holick,2006; Deluca, 2004; Sahota and Hosking, 1999). Key interactions of vitamin D with its receptor are known to initiate gene regulation. These mechanisms have been studied using vitamin D analogues which have revealed the mechanism of assembly of transcriptions factors and promotion of gene regulation by this molecule (Cheng et al., 2004; Wu et al., 2002). Figure 3 shows the effect of various regulators on vitamin D metabolism. Figure 3: Alternate pathway for vitamin D3 under different metabolic conditions of low mineral Ca and P levels, PTH concentration and secretion of GH / IGH (Figure obtained from Gomez, 2006). 1.2.4.1- Parathyroid Hormone Parathyroid hormone (PTH) is the primary regulator of renal 1,25-dihydroxyvitamin D3 formation (Holick, 2006; Dusso et al., 2005; Bouillon et al., 1998; Issa et al., 1998). PTH regulates 1,25-dihydroxyvitamin D3 production directly through enhancing 1-ÃŽ ±-hydroxylase activity within kidney cells and increasing the genetic transcription rate of renal proximal tubular 1-ÃŽ ±-hydroxylase both of which result in an increase in the renal 1,25-dihydroxyvitamin D3 production rate. High levels of 1,25-dihydroxyvitamin D3 suppress the enzyme transcription activity and PTH concentration. Thus, renal 1,25-dihydroxyvitamin D3 has a negative feedback response on PTH secretion, providing an efficient regulatory control of renal 1,25-dihydroxyvitamin D3 homeostasis (Dusso, et al., 2005; Holick,2003; Sahota and Hosking, 1999; Reichel, et al., 1989; Iqbal, 1994). 1.2.4.2- Calcium Dietary calcium exhibits a direct regulatory influence on renal 1-ÃŽ ±-hydroxylase activity via fluctuating serum calcium concentration and indirectly via its effect on serum PTH concentration. Calcium exerts its effect through calcium-sensing receptor (CaR) activation within the parathyroid gland and renal proximal tubules cells in response to low calcium concentration. Thus, the low intracellular calcium levels lead to increased production of 1,25-dihydroxyvitamin D3 within renal cells (Ramasamy, 2006; Bland et al., 1999; Chattopadhyay et al., 1996). On the other hand, it has been shown that high calcium concentrations markedly impair renal 1,25-dihydroxyvitamin D3 formation in human nephrotic cell cultures and in parathyroidectomised animals (Bland et al., 1999; Chattopadhyay et al., 1996). An increase in extracellular calcium indirectly suppresses 1,25-dihydroxyvitamin D3 production at the proximal convoluted tubule by inhibiting PTH release (Deluca, 2004; Carpenter, 1990). Howev er, the detailed mechanism of calcium-sensing receptors (CaR) activation is not yet fully understood (Dusso, et al., 2005; Hewison, et al., 2000). 1.2.4.3- Phosphate Dietary phosphate intake and serum phosphate concentrations exhibit regulatory effects on 1,25-dihydroxyvitamin D3 production in proximal renal tubules. This effect has been demonstrated in several studies which showed that a decrease in dietary phosphate accelerated renal formation of 1,25-dihydroxyvitamin D3, but did not directly affect 1, 25-dihydroxyvitamin D3 catabolism. Conversely, elevated serum phosphate and increased phosphate intake led to decreased production of 1, 25-dihydroxyvitamin D3 (Carpenter, 1989; Reichel et al., 1989). Several studies have shown that inorganic phosphate levels have no significant direct effect on mitochondrial 1-ÃŽ ±-hydroxylase activity in cultured renal cells in the short term, suggesting that the action of inorganic phosphate is not mediated via changes in PTH and Calcium concentrations and is possibly inducted by other hormones such as growth hormone, insulin and insulin-like growth factor (Khanal et al., 2006; Dusso et al., 2005; Carpenter, 1 989). In recent studies, fibroblast growth factor 23 (FGF-23), frizzled-related protein 4 (FRP-4) and matrix extracellular phosphoglycoprotein (MEPE) have all been identified as potent and key regulatory factors of 1-ÃŽ ±-hydroxylase activity in renal cells. These factors act through a biphasic mechanism on renal phosphate homeostasis and modulate the circulating levels of 1, 25-dihydroxyvitamin D3 produced by proximal renal tubules (Dusso et al., 2005; Inoue et al., 2005; Mirams et al., 2004). 1.2.4.4- Calcitonin Calcitonin belongs to a family of calcium regulating hormones that is produced in the parafollicular cells of the thyroid gland, also known as C cells. It is a short and linear polypeptide with a molecular weight of only 3.7 kD. It is characterized by 32 amino acids and a disulfide bridge in the N terminal portion of the peptide. Calcitonin is secreted in response to increased free Ca2+ in blood and acts on osteoclasts, the bone resorbing cells, as a suppressor of bone dissolution. Although calcitonin decreases Ca+2 and inorganic phosphate in blood, it also has the ability to recruit phosphorus into other cells. In addition to these metabolic functions, it is also involved in the upregualtion of CYP27B hydroxylase through the protein kinase C pathway (Yoshida et al., 1999) via a phosphorylation cascade that activates cAMP and induces the expression of hydroxylase thereby activating the transformation of 25(OH) D3 to 1,25(OH)2 D3. In addition to the significant role as a calcium regulating hormone, calcitonin is also known to stimulate the production of vitamin D in tandem with PTH (Yoshida et al., 1999; Wongsurawat and Armbrecht, 1991). Previous studies revealed that 1-ÃŽ ±-hydroxylase mRNA expression, 1-ÃŽ ±-hydroxylase activity and the production of 25(OH)D and 1,25(OH)2D3 all increased in rat kidney cells following the administration of calcitonin (Yoshida et al., 1999; Galante et al., 1972; Rasmussent et al., 1972). However, in cases of diabetes, it is postulated that the kidney becomes immune to the effect of this hormone in diabetic rats which lead to increase vitamin D production (Wongsurawat and Ambrecht, 1991). 1.2.4.5- Growth hormone, Insulin and Insulin-like growth factor-1 Growth hormone (GH) has many regulatory actions in various metabolic processes in humans and mammals and its effect on mineral homeostasis in target organs such as bone and renal cells is well documented. While the regulatory effects of GH on dietary calcium and phosphate metabolism in different tissues have been established, its effect on vitamin D metabolism remains controversial. However, many studies have shown that GH increases the expression of 1-ÃŽ ±-hydroxylase and 1, 25-dihydroxyvitamin D3 in cultured cells and experimental animals (Gomez, 2006). Wu and colleagues reported that serum1, 25-dihydroxyvitamin D3 increases after GH administration in hypophysectomized rats fed with a phosphate depleted diet. Short-term studies in healthy humans have shown that GH raises 1-ÃŽ ±-hydroxylase enzyme activity and promotes 1, 25-dihydroxyvitamin D3 synthesis without changes in PTH, calcium and phosphate concentrations, suggesting that the increasing circulating levels of 1, 25-dihydroxy vitamin D3 following GH administration is not mediated by PTH action (Wu et al., 1997; Bianda et al., 1997; Wright et al., 1996). GH has also been shown to lead to increased production and serum concentration of 1, 25-dihydroxyvitamin D3 in pigs and in renal impaired prepubescent children. These are thought to be a result of the direct and indirect effects of GH on 1-ÃŽ ±-hydroxylase expression, and on calcium and inorganic phosphate homeostasis in renal tubules cells (Strife and Hug, 1996; Denis et al., 1995). However, the action of GH on vitamin D metabolism in vitro remains uncertain and may involve other regulatory factors such as PTH and Insulin-like growth factor-1 (IGF-1). It has been shown that GH does not raise 1, 25-dihydroxyvitamin D3 levels directly in cultured cells obtained from aged-rats; yet it stimulates calcium absorption and the expression of calcium binding proteins in vitro indicating that the effect of GH is mediated through the action of other factors such as IGF-1 (Fleet et al., 1991). Insulin is another key factor with a role in vitamin D homeostasis. Insulin significantly decreases renal hydroxylase activity and renal synthetic capacity of 1, 25-dihydroxyvitamin D3 in insulin deficient patients or those receiving insulin therapy (Armbrecht et al., 1996). However, a study of different routes of therapeutic insulin administration in human diabetic subjects concluded that insulin induces the hepatic hydroxylation of 25-hydroxyvitamin D3. This effect is related to the fact that insulin is a potent inducer of the vast majority of liver hydroxylases enzymes (Colette et al., 1989). This study also showed that there was no significant difference in circulating levels of 1,25-dihydroxyvitamin D3 between different methods of insulin administration. Serum 1,25-dihydroxyvitamin D3 is maintained at normal concentrations in those subjects on long term insulin therapy; however, continuous intraperitioneal infusion procedure (CPII) may augment hepatic 25-hydroxlase activity (Col ette et al., 1989). Similarly insulin has shown a significant effect on stimulating 1,25-dihydroxyvitamin D3 production through 1,25-dihydroxyvitamin D3 and PTH stimulation with no concomitant action on 24-hydroxylase expression in rat osteoblast cells when these cells were cultured with known concentrations of 1,25-dihydroxyvitamin D3 and PTH (Armbrecht et al., 1996). Insulin-like growth factor-1 (IGF-1) is a relatively small peptide that is primarily expressed in hepatic cells and to a lesser extent in some other cells and tissues. It has been identified as one of the potent regulatory components of mineral metabolism in humans and mammals. Recent studies on the metabolic effect of IGF-1 revealed that the administration of IGF-1 to aged laboratory animals, fed on a calcium- and phosphate- deficient diet, can restore 1-ÃŽ ±-hydroxylase activity and enhance the production of 1,25-dihydroxyvitamin D3. In contrast, there was no significant effect of IGF-1 on enzyme activity and 1,25-dihydroxyvitamin D3 levels in adolescent or elderly rats fed on a calcium and phosphate fortified diet concluding that the expression of IGF-1 is not age related but related to the dietary calcium and phosphorus status. (Gomez, 2006; Wong et al., 1997; Wu et al., 1997). In healthy human subjects, a significant effect of IGF-1 on renal 1,25-dihydroxyvitamin D3 synthesis wa s observed after short term infusion with IGF-1. There was no noticeable alteration of the levels of circulating calcium, phosphate and PTH highlighting the role of IGF-1 in stimulating renal expression of 1-ÃŽ ±-hydroxylase and 1,25-dihydroxyvitamin D3 formation in conjunction with GH, independently from PTH (Bianda et al., 1997). In vitro studies have shown that IGF-1 influences the expression of 1-ÃŽ ±-hydroxylase and 1,25-dihydroxyvitamin D3 synthesis in cells cultured from non renal human tissues. Halhali and colleagues demonstrated that IGF-1 noticeably elevates both the enzyme activity and 1,25-dihydroxyvitamin D3 levels when added into cultured syncytiotrophoblast cells obtained from human placental sources. This study demonstrated that IGF-1 strongly enhances the ability of non renal cells to produce 1,25-dihydroxyvitamin D3 without involvement of GH and PTH (Halhali et al., 1997). 1.2.4.6- 1, 25-dihyroxy vitamin D3 The circulating levels of 1,25-dihydroxyvitamin D3 modulate its production by renal cells through an indirect negative feedback mechanism. This mechanism appears to reduce the likelihood of vitamin D toxicity by inhibiting 1,25-dihydroxyvitamin D3 synthesis by an indirect mechanism that controls the 1-ÃŽ ±-hydroxylase gene expression at the molecular level rather than inhibiting 1,25-dihydroxyvitamin D3 synthesis directly. However, the exact mechanism is not yet fully understood (Dusso et al., 2005; Deluca et al., 1990). A recent study examined the effect of 1,25-dihydroxyvitamin D3 on 1-ÃŽ ±-hydroxylase production by cultured human keratinocytes. Keratinocytes were cultured with labeled 25-hydroxyvitamin D3 and different concentrations of 1-ÃŽ ±-hydroxylase mRNA and 24-hydroxylase- suppressed proteins. The 1,25-dihydroxyvitamin D3 did not suppress either the 1-ÃŽ ±-hydroxylase activity or the rate of gene transcription. The study implied that metabolic regulation of 1,25-dihydroxyvi tamin D3 is related to the molecules biodegradation in response to augmented 24-hydroxylase activity rather than 1,25-dihydroxyvitamin D3 formation by 1-ÃŽ ±-hydroxylase (Xie et al., 2002). In addition, Wu and colleagues demonstrated a possible alternative mechanism of 1,25-dihydroxyvitamin D3 synthesis linked to the fact that both 24-hydroxylase and 1-ÃŽ ±-hydroxylase enzymes share equivalent metabolic capability and they proposed the possibility of protein- protein interaction between intracellular vitamin D binding protein and 1-ÃŽ ±-hydroxylase (Wu et al., 2002). 1.2.5- Vitamin D Transport, receptors and mechanism of action Vitamin D receptor (VDR), also known as calcitriol receptor, is a member of the steroid family and belongs to the nuclear receptor superfamily (NHR). Human VDR until recently was thought to comprises four functional units with a total of 427 amino acids residues with an estimated molecular weight of about 48 kDa. These units are the DNA binding domain (DBD) or C domain, the D domain and the ligand binding domain (LBD) or E domain. More recently, a carboxy-group with undefined function, known as the F region has been identified (Christakos et al., 2003; Aranda and Pascual, 2001; Rastinejad et al., 2000). These units as, shown in figure 4, are also known as A/B domain. The A/B region of VDR contains a low number of amino acids that participates in essential ligand-independent receptor stimulation (Aranda and Pascual, 2001; Issa et al., 1998). It is not yet clear if the deletion of A/B domain from VDR will compromise ligand binding, DNA binding or its transactivation features (Issa et a l., 1998). In contrast, the structure of the DNA binding domain or C region among NHRs comprises 40% unique amino acids sequences and a domain of more than 67 resemble amino acids residues (Rastinejad et al., 2000). Moreover, the core structure of DBD comprises between 22 and 114 amino acid residues, nine of them are cysteines. Eight of cysteine residues orchestrate with zinc atoms in tetrahedral fashion to form a dual â€Å"zinc-like finger† DNA binding configurations containing approximately 70 amino acids with a carboxy-terminal extension (CTE). This encloses T and A boxes in a dual helix molecule in which one helix is essential for definitive interaction with the main domain on DNA while the second helix takes a part in receptors structural properties (i.e. receptor dimerization) (Aranda and Pascual, 2001; Issa et al., 1998). However, the integration of the structural amino acids of the DBD ÃŽ ±-helix one, at the site of the first zinc atom, determines the selectivity and specificity of recognition of DBD and forms an area known as the â€Å"P Box†. Similarly; the integration of amino acids at the position of the second zinc atom modulates the formation of a configuration termed the â€Å"D Box† which forms a dimerization interface zone (Aranda and Pascual, 2001; Rastinejad et al., 2000; Issa et al., 1998). Furthermore the vast majority of DBD amino acid units are basic amino acids which enhance the non-covalent binding of the DNA helix at the negatively charged phosphate group (Issa et al., 1998). The ligand binding domain (LBD) or E domain has a spherical configuration with many functional regions composed of 12 cohered helix anchors defined as H1 to H12. LBD itself comprises a net of 427 amino acids which contribute to homodimerization and heterodimerization and the interaction of hormones and costimulaotors by a crucial transactivational mechanism (Aranda and Pascual, 2001; Weatherman et al., 2000; Issa et al., 1998). Crystallograp hic studies show that LBD have two cohered and integrated domains, the Ti or â€Å"signature motif† and the carboxy or C terminal AF-2 providing the self-ligand transcriptional properties; hence a higher degree of attraction of 1,25 dihydroxyvitamin D3 binding is observed at 382 to 402 of LBD amino acid sequence and any genetic aberration at this particular amino acids sequence will diminish the interaction capability of LBD (Aranda and Pascual, 2001; Issa et al., 1998). Figure 4: The primary structure of the vitamin D receptor (VDR) and the binding of retinoid X receptor (RXR)-VDR heterodimers to vitamin D response elements (VDREs) in the form of DR3 and ER6 motifs. (Figure from Lin and White, 2003) 1,25-dihydroxyvitamin D3, has been identified as steroid hormone with a mechanism of action similar to other steroid hormones, causing new protein expression in various target organs. Based on the nuclear receptors structural studies, calcitriol is known to exert its biological action through binding with VDR in the cell nucleus to mediate a cascade of transcriptional and translational processes resulting in either the regulation or inhibition of new protein expression in target tissues or the binding to plasma membrane receptors without stimulating new protein synthesis (Nezbedova and Brtko, 2004; Reichel and Norman, 1989). Two different receptors for 1,25-dihydroxyvitamin D3 have been recognized in different target cells; identified as genomic VDRnuc and typical VDRmem .These receptors provide the best dynamical conformational forms for calcitriol interaction and to evoke its genomic and non-genomic effects (Norman et al., 2002). The binding of 1,25-dihydroxyvitamin D3 to VDRnuc e nhances the interaction with an undistinguished protein known as the nuclear accessory factor (NAF) and to the caroxy-terminal of VDR. This interaction leads to a structural conversion pattern of the C-terminal of VDR allowing the AF-2 domain to attach with other transcriptional elements such as SCR-1, calcium binding protein (CBP) and P300. This promotes the binding of the heterodimer molecule with DNA at the vitamin D response sites (VDRE) and directs its transcriptional gene activity (Jones et al., 1998; Iqbal, 1994). In addition, these coactivators play a role in DNA configurational changes through histone acetyl transferase activation pathway of the core components of histones. This results in mechanical instability of the DNA structure and enhances the net binding capacity of the coactivators with their corresponding receptors at nucleosomal histone level and leads to the upregulation of these transcriptional coactivators which in trun, accelerate the net gene transcriptional rate to promote the synthesis of the analogous protein (Lipkin and Lamprech, 2006; Jones et al., 1998). Conversely, the non-genomic or classical effect of 1,25-dihydroxyvitamin D3 is modulated through its binding with the surface cellular membrane receptor known as mVDR which initiates an immediate response in various target tissues with no genomic transcriptional activity. Many studies demonstrate the rapid effect of calcitriol in rapidly increasing both the level of circulating calcium and its absorption rate in animal intestines, evoking phosphoinoisitide bioactivation, cyclic guanosine monophosphate (cGMP) elevation, activation of protein kinase C and triggering the mitogen activated protein kinase pathways and involving the chloride gates action potential in different organs (Dusso et al., 2005; Nezbedova and Brtko, 2004; Boyan and Schwartz, 2004; Norman et al., 2002). The entire mechanism, as shown in figure 5, for the rapid effect of calcitriol remains doubtful, however; the proposed mechanism is mediated through the interaction with mVDR leading to a series of intracellular sig naling events. Signaling is orchestrated by the activation of various metabolic pathways involving different transportation mechanisms of certain mineral components of target organs. (Pedrozo et al., 1999; Norman et al., 1999; Revelli et al., 1998). However, other studies reveal that the genomic effect of 1,25-dihydroxyvitamin D3 is independent of its non-genomic mechanism (Dusso et al., 2005). Figure 5: Cellular mechanism of action of 1,25(OH)2D3 (Figure from Horst et al., 1997) 1.3- Biological actions of Vitamin D on target tissues and Systems The active form of vitamin D, 1,25-dihydroxyvitamin D3 is well recognized as a member of steroid hormones that mediates several metabolic and non-metabolic processes in various organs in human and animals as shown in figure 6. 1.3.1- Intestine Mineral absorption in the intestines is increased in the presence of the hormone 1,25(OH) vitamin D. However without this, only 10 to 15% of dietary calcium and 60% of phosphorus is absorbed from the diet (De Luca, 2004). Ca2+ and HPO42- are also absorbed when intestinal cells interact with the vitamin D- VDR- RXR complex. The latter enhances the expression of the epithelial calcium channel and calcium-binding protein which recruits calcium and phosphorus (Holick, 2007). Knock out mice experiments studying the effect of VDR gene deletions also show that the size of the small intestines is related to the levels of calcitriol and dietary calcium availability. Vitamin D deficient mice fed with diets low in calcium exhibited the largest small intestine to large intestine ratio (Cantorna et al., 2004). VDR knock-out mice experiments also aid in the discovery of calcium channels, the route for Ca absorption, in the intestine (Peng et al., 1999). Calbindin is a potent calcium transporter in mammals which characterized by a high affinity for calcium ions. Therefore, the binding of vitamin D to VDR and RXR signals an increased production of calbindin which facilitates systemic Ca2+ ions transportation and prevent the occurrence of calcium toxicity in the intestines. Figure 6: Schematic diagram of the effects of Vitamin D on different tissues and organs (Figure from Holick, 2007). 1.3.2- Bone Takeda et al. (1999) studied the role of vitamin D and VDR in bone cells using knock out mice experiments. Their results showed that bone cells formation triggering mechanisms such as cell to cell interaction between osteoblast and osteoclast progenitors and stromal cells induced by 1,25(OH)2 vitamin D3 and provoke the formation of osteoclasts. In their capacity as bone resorbing cells, osteoclasts can be triggered by low serum calcium levels, to break down bone and free calcium back in to the blood thus redistributing calcium throughout the body. However, this does not occur without the expression of VDR and without vitamin D complexing with its receptor. This study emphasizes the important role of recognition sites on the VDR and the structural implications that the receptor-ligand binding has on VDREs and transcription initiation. Although the effects of PTH

A Family Vacation to Canada :: Summer Vacation Essays

This is the actual story of a trip I took with Smith Family into Canada. The total head count was 19, including myself. The trip took 8 days to complete. We left on Saturday, June 24 at 12:00am and got back on Sunday July 1, around 3:00pm. The great Canadian adventure started at 12 noon on Saturday to pack the bus and truck. The bus is an old school bus with a big rack on top to hold canoes, and screens over all the windows. Inside there are 8 bunks in the back for sleeping. The middle is where the food is kept. The front has two tables on each side for playing cards. As soon as I got there I started meeting people. I had only met Craig, Renee, and Amber before at Cameron Smith’s graduation party. There were 3 well fed dogs running around. The first person Tyler pointed out was Harry, his grandpa. He was getting the gas together for the boats and there were about 5 others standing around him. One was Troy and the other was Larry. It was easy to see that Craig and Troy were brothers, they were rigging the bus to carry 5 canoes. Others were busy helping to get ready. I helped put the motor rack in Tyler’s truck. After the bus and truck had all of the canoes on, Jeff, Tyler, and I went back to Tylerâ₠¬â„¢s house to take showers and eat. The plan was to meet Craig at Cash Wise at 8:30 to buy the food. Craig’s Eagle got a flat tire on the way to Willmar. Tyler, Jeff, and I got there at 9:30 but the shopping was already done. As we were leaving Willmar, on our way back to Harry’s, we were able to see fireworks from the â€Å"Works over Water† display on Foot Lake. When we got to Harry’s, there were several cars in the yard. Tyler and I went to the house were I met Erin and Allison for the first time. Erin was eating a pizza and at first glance I thought she was Emily Smith. I could not get over how much Erin, Allison and Amber looked like Emily. Little kids were running everywhere. In the living room, were about 25 people I had never met or seen before, who seemed to be having a good time together.

Tale Tell Heart and Goose Girl

Jack Mitchell Mr. Glen Smith English1302 Oct 10,2012 Compare/Contrast Essay Assignment #2 The unnamed narrator in Edgar Allan Poe’s â€Å"A Tell- Tale Heart† and the chambermaid in the Grimm Brothers â€Å"The Goose Girl† both possess strikingly similar characteristics. Both show aggression and use violence to get what they want but are very careful of how they go about it and covering it up. In Poe’s story, the unnamed narrator kills an elderly man that he is caring for because the old man has a foul looking eye that is covered with a white film.This is what is slowly driving him insane but afterwards he ingeniously decides to hide the body incase someone heard the noise of the olds man body. This is so he does not get arrested for his murder and when the police do stop they believe his story and do not suspect anything, until he gives them a reason. The chambermaid on the other hand forcefully and violently makes the princess, who she knows wont stand up for her self, switch places with her simply because she wants to live the life of the princess.She also makes the princess swear to secrecy so she never has to worry about her true identity being unveiled. Later, she cleverly kills the princess’s talking horse, which was the only witness to what happened between the chambermaid and the real princess’s. In Poe’s â€Å"The Tell-Tale Heart† the unnamed narrator is caring for an elderly man who isn’t capable of taking care of himself. The elderly man has a bad eye that has a silky film over the top of it. The narrator becomes sickened and essentially afraid of the eye.He decides that the only way he can get rid of these feelings is to kill the old man thus getting rid of the eye forever Originally, he is hesitant to actually go through with his plan, but he knows it is the only way to end his torture. â€Å"I made up my mind to take the life of the old man, and thus rid myself of the eye forever† (303). He waits until the time is right when the eye is open to kill him â€Å"I did for seven long nights every night just at midnight, but I found the eye always closed; and so it was impossible to do the work† (303).He feels he must kill the man with the evil eye open because â€Å"for it was not the old man who vexed me, but his Evil Eye† (303). Once he finally kills the man, he decides to hide the body incase someone heard the noise or the beating of the man’s heart, which is now driving him even more insane. However, when he was finished cleaning up someone rang his doorbell and when he opened it, â€Å"There entered three men, who introduced themselves, with perfect suavity, as officers of the police† (305). The narrator gave the police a very believable story and they were satisfied.He was almost scott free, but then he starts to hear the thumping of the mans heart and starts going crazy. Convinced the police heard the noise too he ripped up th e planks revealing the body of the elderly man. In the Grimm Brothers â€Å"The Goose Girl†, the chambermaid of the princess so desperately wants to the live the lavish care free life of the princess she decides to test her fate by taking action. This is when her violent behavior is seen for the first time, when she decides to forcefully and violently begin to curse at the princess to dress up as a chambermaid so she can take the princess’s place.She also made the princess to swear to never tell anyone what happened. â€Å"Then with many harsh words, the chambermaid ordered the princess to take off her own royal clothing and put on the chambermaid's shabby clothes. And in the end the princess had to swear under the open heaven that she would not say one word of this to anyone†¦Ã¢â‚¬ (406) When she finally arrives at the castle and marries the king, she asks him for a favor. â€Å"Send for the knacker, and have the head of the horse which I rode here cut off. â €  (408) This is her way of making sure that there are no loose ends and that there is no one or thing that can revel her true identity.However, she does not know the horse can still talk after its’ been beheaded. This small overlooked detail is the root cause to her downfall. The Narrator is portrayed as an insane man who starts to lose control of whatever sanity he has left once he comes into contact with the elderly mans grotesque eye that he thinks is evil. Even though he is portrayed as crazy, in reality he has not lost his mind completely, in he fact that he actually watches the man, investigates the room, and checks the eye to see if it is open â€Å"every night just at midnight†(303). He did this for seven nights, hich clearly shows that he has not completely lost his grip on reality. By waiting for the perfect chance to strike shows patience, mentally and physically. Another sign the narrator was not totally insane was that he had a face-to-face conversatio n with three police officers. In the end, â€Å"The officers were satisfied† and believed his alibi. There is no way a person said to have lost his mind completely could have fooled three trained police officers. On the other hand, the chambermaid in â€Å"The Goose Girl† is seen as a cunning, tough character throughout the story.However, towards the end of the story her true colors begin to shine. By her sending out the knacker to â€Å"have the head of the horse which I rode here cut off, for it angered me on the way. †(306). This shows that she has started to worry and stress over her secret getting out. By her having everything and everyone who could tell her secret around her taken away is the first sign of weakness from her. It is a sign of weakness because she is doing everything possible to save herself and only herself.Lastly, the reason why both the chambermaid and the narrator both got caught and failed to get away was due to them. The narrator was ho me free until he started to panic, thinking the guards could hear what he was hearing he finally lost it â€Å"dissemble no more! I admit the deed! —tear up the planks! here, here! —It is the beating of his hideous heart! † (306). The chambermaid had it done what she had set out to do. However, if she would have stopped and trusted the promise the princess gave her from the beginning she would have been fine.She instead decided to take things into her own hands and had the talking horse beheaded. Finally, the reader can see that both of the characters used every means necessary to get what they wanted which included violence to get what they want but are also very careful of how they go about it and covering it up.Work Cited Grimm, Jacob and Wilhelm Grimm. â€Å"The Goose-Girl. † Kinder-und Hausmarchen. 7th ed. D. L. Ashilman, trans. Berlin: n. p. , 1857. Print Poe, Edgar Allan. â€Å"The Tell-Tale Heart. † The complete Tales and Poems of Edgar All an Poe. New York: Random House, 1975. Print.