Reflection Of The Movie Amistad - 1426 Words

Amistad 1. What is the Central message of this motion picture? The fact that the freedom that we experience today did not come easy, many things had to happen in order to get where we are. 2. Was the film effective in communicating this message? In what ways? Yes, the film showed what it was like back in the day when people from Africa were forced to leave their homeland and become slaves against their will. It showed how the case against the Amistad Africans led to political changes in the U.S. which then had an effect in the rest of the world. 3. How do you think the filmmakers wanted the audience to respond? They probably wanted people to realize and see how bad things really were sometimes. They wanted people to see what the history†¦show more content†¦We take this for granted, but is freedom worth dying for? Do you appreciate the sacrifices that have been made so that you can live free? I believe freedom is worth dying for as long as there is certainty that it will be obtained in the end. I definitely appreciate the sacrifices that people have made and are making today, so that we may live free lives. 9. Has this film helped you to understand the common undergirding that every person feels to be free? How? Give an example. Yes, this film has helped me see that people see freedom as a natural right, something that shouldn’t be taken away from anybody. An example would be the people who have escaped from North Korea, they knew if escaped, then their families would suffer the consequences, but they didn’t see it as bad thing since they knew there wasn’t a very bright future in their country to begin with. So, they escaped to truly live and to be free. This movie really changed my perspective on history, but especially on the history of African-Americans and slavery. Seeing how innocent people who had done nothing to deserve such cruel and terrible inhumane treatment by the hand of others who saw them as inferior, suddenly found themselves being trapped, beaten, stripped of their clothes, families, and belongings, it was very hard for me to wrap my head around the fact that this actually happened. When one tries to imagine what it would have been like if we had been born in that time a nd eraShow MoreRelatedAmistad Movie Reflection748 Words   |  3 PagesIn the movie Amistad there are many instances where African Americans are treated very poorly, just like they were not even the same creature the captors were. I have watched this movie and thought it over thoroughly afterwards. I was tasked after thinking it over the answer the question of â€Å"How could someone’s conscience allow them to treat another human being so horribly?† I find this answer very obvious throughout the film. These men performing these heinous acts of injustice against these AfricanRead MoreAnalysis Of The Book Amistad By Steven Spielberg And Howard Jones Book, Mutiny On The Amistad Essay1972 Words   |  8 Pagesâ€Å"Amistad† movie is directed by Steven Spielberg and Howard Jones’ book â€Å"Mutiny on the Amistad: The Saga of a Slave Revolt and its Impact on American Abolition, Law and Diplomacy† are historical accounts of the slave mutiny that occu rred in the year 1839. The incident happened when the slaves at sea, aboard on La Amistad. Spielberg’s movie depicts the incident in visual word, whereas Jones’ has written the book and depicted the entire incident by using words. Both mediums capture the case that hadRead MoreHistory3115 Words   |  13 PagesKampung Baru Cina was opened, the sacrifices of the Malay in sharing their country and privileges, and how the Malay Kings had never given up the sovereignty of their states to the British, she added. â€Å"Colloquiums such as this are not merely a reflection on history, but a chance to revisit to correct misinterpretations so that the minds of the younger generation are on the right track,† shesaid. She called for all the main locations for communist attacks to be gazetted and for the struggles of

Understanding The Looking Glass Self - 1129 Words

A wise sociologist once said, â€Å"In order to be -- or become -- fully human, humans need a great deal of proficiency at taking account of others and forming relationships with them.† Sociology teaches humans where we connect to different groups as well as classifying them into these groups. These classifications that we are assigned include, economic status level, education, ethnicity, and sexual orientation. By doing so, we perceive the view of ourselves and others in the world. The Looking Glass-Self allows us to see our interactions with others as well as what they expect from us according to our behavior (Verderber, 34). That is what sociology is; the study of society and social interaction. Throughout our lives, we have learned and will still continue to learn how to function as a â€Å"normal† human being. What defines normal? Although there are many definitions to this word, one may define it as average. It all depends through the eye of the beholder which is filtered through the lens of society. What that means is, your definition of â€Å"normal† might not exist on its own, but it is created by observing the way of life through your own perspective and experiences. The way I see defining â€Å"normal† is through your own social behavior. When speaking to someone for the first time, the way you come off to others will make them decide whether you are normal or not. You are learning to create relationships by the culture that is formed around you. Culture teaches you and yourShow MoreRelatedWhat I Have Learned From A Social Theory Class1240 Words   |  5 Pagesmajor publications, Mind, Self, and society, The philosophy of the Act and The Philoso phy of the present. He is also Pioneered the development of symbolic interaction perspective which is a school of thought in sociology that explains social behavior in terms of how people interact with each other (http://www.chegg.com/homework-help/definitions/symbolic-interactionism-49). Mead argued that interaction is the key to understanding human behavior and that there can be no self apart from society, noRead MoreMy Social Science Requirement For My Associate Degree923 Words   |  4 Pagesinterested in the theories that sociologist came up with. When I started reading the modern development theorists, Charles Horton Cooley, it was so fascinating because he focused on social interaction. Cooley came up with the concept called â€Å"looking glass self†, and I will explain it and show my view about it in this essay. Charles Horton Cooley was born during the 18’s. He grew up in wealthy life where his father and mother had professional jobs in the industry. He was lonely and shy personRead MoreSocial Construction And Disability Models1579 Words   |  7 Pagesdeaf culture lying at the heart of the linguistic minority construction. Advocates of the disability construction for all the deaf people use the term â€Å"deaf community† to identify people with significant hearing impairment. Medicalization and Looking Glass Self Medicalization is the process by which a phenomena is defined as within the purview of medical expertise and intervention. The trend in our society is toward greater medicalization, and focused on seeing more and more things as in the realmRead MoreAlice s Journey Through Looking Glass World1415 Words   |  6 PagesThe Victorian Era was a time of great innovation and new idÐ µas to voice their people on a variety of different subjects ranging from politics to social structure. Lewis Carroll, a popular authÐ ¾r of the time, Through the looking Glass, which serves to help readers understand children. Children in the era were previously considered unimportant and empty-headed, but Carroll shows, through Alice’s interactions with various characters, how one could be much more intelligent and mature than adults ofRead MoreSymbolic Interaction Theory : The Looking Glass Self And Romantic Relationships1126 Words   |  5 Pagesinteraction with others. Symbolic interaction theor y has greatly impacted our world. This theory helps one understand how individuals shape their own reality and create norms. This essay focuses on the symbolic interaction theory through the looking-glass-self and romantic relationships. Symbolic Interactionism focuses on face-to-face communication. It is also micro-level theory; meaning this theory covers very specific relationships between individuals or small groups. Micro level theories areRead MoreHow I Changed My Life771 Words   |  4 Pagesand how I interact with society. Understanding how I have been affected by my immediate surroundings is a significant part of a better understanding how I have been changed by the greater society. All through this semester, I have begun to reminisce back on my life and pull apart the different ways that I have been affected and how they can be looked at sociologically. The first thing that I genuinely began to break down was the way I distinguish myself. My self-identity is something that I haveRead MoreThe Concept Of The Looking Glass Self1423 Words   |  6 Pagessociology actualized questions of understanding the nature of the individual. This determined the weakening of the behaviorist tradition, which is characterized by a nihilistic attitude to the study of psychological processes and the determination of the human life as a manifestation of the externally observable behavior (by analogy with the animal reaction). The interactionist approach in sociology has been formed and it refers to the integrity of the human personality and self-determination in the micro-socialRead MoreCharles Horton Cooley s Concept Of The Looking Glass Self870 Words   |  4 Pages1902, Charles Horton Cooley fashioned the concept of the looking-glass ‘self,’ this concept was researched to learn how identity is shaped. The authors concluded that people shape their identity based on the perception of how they think others view them. Three ideas comprise the looking-glass ‘self’: First, we see in our mind’s eye how we appear to others, second we imagine their judgment of how we appear to them, and third we develop our ‘self’ (our own identity) receiving the judgments from othersRead MoreFreud id, ego, superego954 Words   |  4 Pagesï » ¿ To become a healthy adult socially, mentally and physically Freud believed that children must develop a reasonable balance between id and superego. Id is the natural, unsocialized, biological portion of self, including hunger and sexual urges. Superego is composed of internalized social ideas about right and wrong. When describing the effects of socialization: the process through which people learn the rules and practices needed to participate successfully in their culture and society, PeterRead MoreThe Looking Glass Self By George Herbert Mead831 Words   |  4 Pageswas on the mind he developed a sense of self and opened up discussions about the impact of subject and creativity on society to the rather objective approach to the constitution of society. Cooley saw himself as less of a sociologist than as a scholar in history, philosophy and social psychology. The looking glass self was introduced in his book Human Nature and the Social Order the primary group was introduced in Social Organization. The looking glass self describes how an individual develops his

World War II Free Essays

World War I couldn’t have ended any worse. The way it was handled was wrong and as a result of that, a war even worse than before broke out. The three main causes of World War II were the ways France, Britain, and Germany handled it diplomatically, socially, and financially. We will write a custom essay sample on World War II or any similar topic only for you Order Now There are sources that show the actions taken by the countries. After World War I France had made a treaty with the country of Poland that states if either country is attacked, the other will send aid and assistance via money and manpower, â€Å"to lend each other immediate aid and assistance, if such a failure is accompanied by an unprovoked recourse to arms†¦Ã¢â‚¬  (Doc 5) This was a key factor in why France went to war against Germany after Poland was invaded by Germany. In an excerpt of Benito Mussolini, What is Fascism, he mentioned that Fascism is â€Å"a force limited to the function of recording results. (Doc 7) Germany was on a conquest to eliminate all of the inferior races, because they weren’t fascist. In a document by British Foreign Secretary Anthony Eden it was said that Hitler would go against any treaty even if he wanted to sign it in the first place, â€Å"We must be prepared for him to repudiate any treaty even if freely negotiated†¦Ã¢â‚¬  (Doc 9) This would prove to be true when Hitler went against the Non-aggression pact he signed with Russia. As a result of World War I, many countries were looking for someone to blame for the destruction caused. The allies, led by France and Britain, put all the blame on Germany in the Treaty of Versailles, â€Å"The Allied and Associated Governments affirm and Germany accepts the responsibility of Germany and her allies for causing all the loss and damage†¦Ã¢â‚¬  (Doc 1) While Hitler was in prison, he wrote a book called Mein Kampf; in the book he wrote how Jews were the absolute opposite of the Aryan, who was the ones who contributed the most to society, â€Å"The Jew forms the strongest contrast to the Aryan. Hardly in any people of the world is the instinct of self-preservation more strongly developed than in the so-called ‘chosen people’†¦? (Doc 4) After Hitler became Chancellor all Germans started to buy in to beliefs similar to this. In a draft for a student composition on the advantages of war, it is said that War is great and to do anything for the Fatherland is the highest honor one could have. â€Å"It is sweet to die for the Fatherland. The dead of the enemy live in the memory of the victor. † (Doc 6) Hitler used these kinds of beliefs to get his country into believing taking over the world was possible. In 1929 the Great Depression struck the United States, shortly after it spread all over the world. This is widely known to also be a cause of World War II. As part of the Treaty of Versailles, Germany was forced to be broken up. West Prussia was separated and was soon on a downward spiral to collapse after economic decay. The German delegation had this to say on the move, â€Å"East Prussia is to be completely cut off from the rest of the empire and thereby condemned to economic and natural decay. † (Doc 2) An author wrote about how the way life was like, was beyond anything ever imagined. â€Å"What we believed to be the limits of possibility have been so enormously exceeded. (Doc 3) No one had taken a hit from the economy going down the drain then Germany. Their employment rate was at an all time low. Heinrich Hauser had this to say about the homeless situation. â€Å"An almost unbroken chain of homeless men extends the whole length of the great Hamburg-Berlin highway. † (Doc 8) If they were to repeat the actions the Allies took after their victory in WWI, I’m sure they would have done it much different. They should have been more lenient on Germany and worked together. There is no doubt that their harsh actions only angered Germany even more and caused the Great War known as World War II. How to cite World War II, Essay examples World War II Free Essays string(24) " a province of Prussia\." The Second World War was one of the most devastating moments in the history of humanity. The conflict claimed the lives of millions of people throughout the world; the number of fatalities actually make it the most fatal in history. The war also proved to be costly; the global damages amount to trillions of dollars. We will write a custom essay sample on World War II or any similar topic only for you Order Now Years prior, the First World War occurred. Those involved in the first conflict tried to take the necessary precautions to avoid another international war from taking place. Unfortunately, it was this attempt that caused the second war to occur. This research paper aims to discuss how the First World War resulted in the occurrence of the Second World War. The First World War ended on November 11, 1918. The experience of such war required the creation of a peace settlement. In January 1919, the countries which emerged victorious in the war sent their representatives to gather in Paris. The said assembly would make political decisions that would influence international relations. The decisions were mostly influenced by the heads of the Allied states. These are France Premier Georges Clemenceau, British Prime Minister David Lloyd George, and Italian Prime Minister Vittorio Orlando and United States President Woodrow Wilson . Prior to the armistice that ended the First World War, President Wilson had already formulated a plan to establish peace. In a speech he delivered to Congress, Wilson announced the â€Å"Fourteen Points,† a set of provisions that would restore world peace. Among the fourteen provisions, three are notable. One of which is the â€Å"peace without victory† clause. Wilson thought that the aftermath of the war should not bring victory, but instead it should bring peace. He also thought that Germany must not be given cruel punishment or else it would provoke the country to avenge its loss. For Wilson, the appropriate penalty would enable the defeated parties as well as the Allied powers to have peaceful relations. Another provision which Wilson suggested was disarmament. Wilson upheld the belief that only through disarmament can peace be truly achieved. If each country were disarmed there would be no threats of war or invasion. He also thought that issues between nations must be discussed openly. Moreover, Wilson suggested the establishment of an organization which could serve as the platform in which international disputes can be settled and wars could be prevented. He referred to it as the League of Nations. The provisions that Wilson suggested may have born out of noble intentions, but it was contrary to what the European Allies wanted. European nations involved in the war were bitter over what had occurred. This holds true for France. Most of the battles occurred in France; many soldiers and civilians were killed. The French were still threatened by what Germany was capable of doing. Therefore, as opposed to what Wilson suggested, France wanted to severely punish Germany and render it incapable of waging yet another war. The aftermath of the First World War included the signing of several peace treaties. However, the most notable was the Treaty of Versailles. It was a peace treaty agreed upon by the Allies and Germany. The creation of the treaty began on January 18, 1919 at the Paris Peace Conference; it was signed on June 28th that same year at the Palace of Versailles. It was this treaty that primarily caused the Second World War to occur. This is because aside from punishing Germany through reparations, it made Germany solely responsible for the occurrence of the war. The Germans reacted to the treaty with much disdain; this is why when Adolf Hitler came to power, he sought to abolish the treaty. The provision President Wilson made about the League of Nations was established through the Treaty of Versailles. Those nations who were part of the League had to recognize the boundaries of the other member nations; they also had to bring all contentions to the League for settlement . Over sixty countries were part of the League, excluding the United States. The absence of the United States in the League proved to be a disadvantage for the organization. On the other hand, Wilson’s wish against the severe punishment of Germany was not granted. The Treaty of Versailles had Germany at the losing end of the agreement. It was responsible for the decreasing not only Germany’s territory, but its power in general. The penalties given to Germany were so harsh that the treaty was criticized by many. Armstrong wrote, â€Å"On the whole, when rights were not in conflict, the Conference tried to base its decisions on high principles; when rights were in conflict it usually favored the victors. This statement held true for the treaty. The treaty prioritized the rights of the Allied nations over the rights of Germany. For instance, France emerged victorious in the war. Most of the demands of the French were considered and granted by the treaty. France was able to regain possession of Alsace-Lorraine as indicated in Section V of Part III of the treaty. As payment for the coal mine destruction, Germany also has to hand over control of the Saar Basin to France, as indicated in Article 45 of Section IV. However, one significant loss of Germany involved the Polish Corridor. Created after the First World War, the Polish Corridor was an area of land which detached East Prussia from Germany. The city of Danzig near the Baltic Sea was made a free port by the treaty. Both Poland and Germany had no control over this territory. However, it was inappropriate for the treaty to remove the Corridor from Germany; this is because Germany was not to blame for the seizure of this territory. It was Prussia, not Germany, who seized the Corridor from Poland. King of Prussia Frederick the Great was the one responsible for the territorial loss of Poland. The Corridor was only included in the territory of the German Empire as a province of Prussia. You read "World War II" in category "Papers" It is crucial to note that the corridor formerly known as West Prussia was never really recognized as a territory of Germany. Hence, to punish Germany by taking away land the nation did not seize in the first place was unjustified. The Treaty of Versailles also demilitarized Germany in very specific terms. As included in the â€Å"Military, Naval and Air Clauses,† the treaty states that the German army must only consist of ten divisions: seven for infantry and three for cavalry. The entire army must only be composed a hundred thousand individuals. The treaty even forbade Germany from importing weapons or using poisonous gases or liquids. Meanwhile, in Article 42 of â€Å"Political Clauses for Europe,† both banks of the Rhine River were made free from German military occupation. Such rules were resented by the Germans; it was therefore no surprise that the first thing Hitler did when he came to power was to restore the military forces of Germany, eventually causing the Second World War. The Treaty of Versailles also seized all of Germany’s foreign territories. Article 119 states that â€Å"Germany renounces in favour of the Principal Allied and Associated Powers all her rights and titles over her overseas possessions. † These include areas in Asia, Africa and the Pacific. Through mandates given by the League, the German colonies in Africa were placed under French and British control. However, the gravest imposition of the Treaty of Versailles on Germany was the War Guilt Clause. Article 231 states that â€Å"Germany accepts the responsibility of Germany and her allies for causing all the loss and damage to which the Allied and Associated Governments and their nationals have been subjected as a consequence of the war imposed upon them by the aggression of Germany and her allies. † The treaty had singled out Germany as the only country to blame for the occurrence of the First World War. This stand was based on a report by the â€Å"Commission on the Responsibility of the Authors of the War† headed by Robert Lansing, the U. S. Secretary of State. During the Committee’s deliberations, Lansing made sure that there was no German involved in the process. The claim was considered as false, prompting American historian H. E. Barnes to ask for the clause to be revised. Despite the invalid claim of the War Guilt Clause, Germany still signed the Treaty of Versailles. This is because the German representatives were forced and threatened to sign the treaty. The clause demanded that Germany should pay reparations to the other countries involved for the damage the war caused. The reparations totaled to $33 billion, an amount only settled years after Germany agreed to the treaty. Germans disagreed with such amount because the nation was incapable of paying that great sum. Germany also argued that they are not the only one to blame for the war. German aggression, which contributed to causing the war, was retaliation against the Treaty of Versailles. From the start, Germany disagreed with the harsh penalties stated in the treaty. The treaty made Germany the only party to blame for the First World War. As punishment, the country was stripped off its military capabilities and its foreign territories. In addition, the treaty demanded a significant sum of money for war damages. When Hitler became powerful, he disobeyed the treaty. Not only did he strengthen the German army, he also sought the return of the Polish Corridor to Germany. The Treaty of Versailles was a crucial contributor to the occurrence of the Second World War for many reasons. The end of the First World War made the international community seek for ways in which to preserve world peace. In addition, they wanted to establish fairness and rapport among the countries after the way. The Allied nations created a treaty in hopes of reaching these objectives. Unfortunately, the treaty failed to fulfill its goal. The reason why the Treaty of Versailles did not work was because it was flawed from the beginning. From the start, it was not feasible to try to achieve peace immediately after such a brutal war. It is also ridiculous to try to be just in dealing with every country involved. For example, France wanted Germany to be severely punished because France was greatly affected by the war. Because the affected parties want revenge against Germany, the treaty that was established on good intentions eventually resulted in more damages. The noble intention of seeking peace and justice was contrary to how the Treaty of Versailles was made. Upon entering the peace negotiations, both Britain and France already sought to seek revenge. Germany and Russia were deliberately left out of the Peace Conference. To make matters worse, reparations were being demanded from people who were already affected by war. All of these contributed to causing the Second World War. Vindictive sentiments played a significant part in the ineffectiveness of the Treaty of Versailles. The Treaty of Versailles was the initial attempt in attaining peace. There were other ways in which peace was tried to achieve after the war. There was the Washington Conference, in which it was agreed that nations would only have a certain number of ships and have the same opportunities to access China. Then there was the Locarno Pact in 1925; in a conference held in Switzerland, countries agreed that all conflicts would be resolved peacefully. One of the specific areas of concern during that time was French-German border. Lastly, there was the Kellogg-Briand Pact in 1928. Fifteen countries participated in an agreement which condemned war as â€Å"instrument of national policy. † Both pacts served to establish peaceful settlement as substitute to force. In the long run, these attempts at peace proved futile. The aftermath of the First World War brought much dissatisfaction to both winners and losers. The dissatisfaction of Germany is understood. It lost in the war, and was blamed for it. The Treaty of Versailles â€Å"humiliated† Germany with such severe impositions. Instead of encouraging peaceful relations, the treaty was punitive in nature. Such punitive effort will never achieve peace. In addition, the losses of Germany in the war were significant. Many people were killed, while damage to property was also notable. The treaty’s terms in which Germany would pay a great sum for war damages already added insult in injury. Such harsh punishment prompted strong nationalist sentiments, which contributed to German aggression in the Second World War. The Treaty of Versailles also failed to address the concerns of Italy and Japan. Italy was dissatisfied with what it had gained from the war. At that time, the country was already experiencing internal conflicts. The â€Å"diplomatic frustration† of Italy as result of the First World War added to the problem. The parliamentary system of government was eventually replaced with fascism. Fascism, under Benito Mussolini, made Italy more aggressive in war. Japan was also dissatisfied with its diplomatic status after the war. Though Japan was a victor in the First World War, the country was frustrated because it wanted more than what it gained. Japan believed that they should be the stronger force in Asia. This sentiment was driven by the influence of the military, as well as nationalism. All three countries were frustrated with the outcome of the First World War. These nations also felt economically deprived after the war. All three criticized the lack of equal access to â€Å"raw materials, markets and capital investment areas,† which contributed to the decline of their economic stability. In turn, the nationalist feelings in all countries brought out vindictive sentiments. Thomas Hobbes once wrote that people would â€Å"choose rather to hazard their life, than not to be revenged. These countries felt the injustice; another war seemed to be an ideal venue in which revenge could be taken. The Treaty of Versailles also caused the war through the League of Nations. It is true that the League was created to establish peace after war, but in reality the League was powerless to do so. The absence of the United States made a huge impact on weakening the power of the League. It was not influential enough to enforce necessary penalties on offenders. There are several examples in which the League of Nations proved ineffective. When Italy attacked Ethiopia, the emperor of the latter reported to the League. Italy only denounced the invasion. The organization asked its members to stop selling weapons and commodities to Italy, but only a few obliged. Ethiopia eventually became a colony of Italy. The Treaty of Versailles also caused Japanese aggression against China. The treaty removed all the foreign possessions of Germany. Japan benefited from this removal, as it gained territories in the Pacific as a result. However, the Shantung Peninsula was left unresolved. The issue was to be settled between Japan and China. This created conflict, and Japanese aggression toward China soon started with the Manchurian invasion. The takeover was denounced by the League, but that was all it did. Japan left to League, and continued to threaten China. The First World War caused the occurrence of the Second World War. The Treaty of Versailles was the primary cause. The treaty was supposed to establish peace after such grueling conflict, but it only resulted in another, more fatal war. To begin with, the process in which the supposed peace settlement was created ran contrary to its intentions. Victors such as France and Britain was preoccupied with revenging their losses. This meant that their demands included in the treaty were based more on revenge than on the intention of achieving peace. Such vindictive attitude greatly influenced the drafting of the treaty. The vindictive intention in the drafting of the Treaty of Versailles also caused German aggression. In general, the treaty was created to punish Germany. Many people thought the terms were too severe. This included limiting the German military and losing several territories. The most notable of these territories was the Polish Corridor, a territory that taken from Germany as stipulated in the treaty. In addition, there was the War Guilt Clause, the false claim which stated that Germany was the only one responsible for the war. Such terms caused much resentment from the German people. This prompted Adolf Hitler to be aggressive, and undo the damages caused by the treaty. The Treaty of Versailles also did not address the needs of Italy and Japan, which caused them to also be aggressive. Italy and Japan were disappointed with the outcome of the war. Along with Germany, both countries were economically frustrated. Another war provided the venue to gain what these countries thought they deserved. Lastly, the League of Nations created through the treaty was ineffective and powerless. It could denounce acts of violence against nations, but it was unable to exert any real influence. The organization had no power to prevent one nation from attacking another. In the end, in an effort to avoid war, the consequences of the First World War brought about the more massive Second World War. Neither peace nor justice was achieved; there was only more violence. How to cite World War II, Essays World War II Free Essays

English Language and Linguistics Introduction To Systemic Functional

Question: Describe about the English Language and Linguistics for Introduction To Systemic Functional. Answer: Ice Hockey may be probably one of the most exciting games to follow presently but few people know the rules. Ice hockey may be probably One of the most exciting games To follow presently Subject Finite: modality modalization Mood Adjunct: probability complement predicator Adjunct MOOD RESIDUE But Few people know The rules Subject Finite present Adjunct MOOD RESIDUE One cannot possibly play ice hockey today if he is not a good skater. one cannot possibly play Ice hockey today Subject Finite: modality modalization Mood Adjunct: probability predicator complement Adjunct MOOD RESIDUE If He Is not A good skater Subject Finite present Adjunct MOOD RESIDUE Evidently every ice hockey player must be an expert in skating presently because else they might get injured . evidently Every hockey player Must be An expert In skating presently Mood Adjunct: probability Subject Mood Adjunct: probability Complement predicator Adjunct MOOD RESIDUE Because else They might Get injured Subject Finite present Adjunct MOOD RESIDUE The punk would probably hit the ice so fast that it travels 100 miles an hour. The punk would probably Hit The ice So fast Subject Finite: modality modalization Mood Adjunct: probability Predicator Complement Adjunct MOOD RESIDUE That it Travels 100 miles an hour Subject Finite present Adjunct MOOD RESIDUE The players would require hitting the punk with the sticks and the sticks long L-shaped. The players would require hitting The punk With the stick Subject Finite: modality modalization Mood Adjunct: probability Predicator Complement Adjunct MOOD RESIDUE And The sticks Are long L-shaped Subject Finite present Adjunct MOOD RESIDUE Ice hockey can probably be a game in this time that takes great skill and courage. Ice hockey can probably be A game In this time Subject Finite: modality modalization Mood Adjunct: probability Predicator Complement Adjunct MOOD RESIDUE That takes Great skill and courage Subject Finite present Adjunct MOOD RESIDUE One should not probably play this game ever if he is afraid of injury. one Should not probably play This game ever Subject Finite: modality modalization Mood Adjunct: probability Predicator Complement Adjunct MOOD RESIDUE If He is afraid of injury Subject Finite present Adjunct MOOD RESIDUE The game comes with a handy set of injuries always which is hard to ignore. The game Comes with A handy set of injuries always Subject Finite: modality modalization Mood Adjunct: probability Predicator Complement Adjunct MOOD RESIDUE Which is Hard to ignore Subject Finite present Adjunct MOOD RESIDUE Ice hockey may probably be undoubted always as an exciting game to follow. Ice hockey May probably Be undoubted Always Subject Finite: modality modalization Mood Adjunct: probability Predicator Complement Adjunct MOOD RESIDUE As An exciting game to follow. Subject Finite present Adjunct MOOD RESIDUE The punk must be probably the most important part in the game which is a small piece of rubber. The punk Must be probably The most important part in the game subject Finite: modality modalization Predicator Complement Adjunct MOOD RESIDUE Which Is a Small piece of rubber. Subject Finite present Adjunct MOOD RESIDUE Reference: eggins, s. (2016).An Introduction To Systemic Functional Linguistics. 2nd ed. london: Continuum international Publishing Group. Gee, J., 2015.Social linguistics and literacies: Ideology in discourses. Routledge. Martin, J.R., 2014. Evolving systemic functional linguistics: beyond the clause.Functional Linguistics,1(1), p.1. Matthiessen, C. M. (2012). Systemic Functional Linguistics as appliable linguistics: social accountability and critical approaches.DELTA: Documentao de Estudos em Lingstica Terica e Aplicada,28(SPE), 435-471.

Jurassic Park Essays (478 words) - Jurassic Park,

Jurassic Park Jurassic Park takes place on an Island off the Coast of Costa Rica which is owned by a multimillionaire, John Hammond. On this island he has set up a genetical engineering facility which permits him and his scientist to create dinosaur from blood extracted from prehistoric mosquitos, that have been preserved in amber. Before he opens this living attraction to the public he needs specialist to approve the park. He brings them to the island and begins to show them what he has accomplished. While they are touring the island one of the computer programmers, Dennis Nedry, is secretly planning to steal dinosaur embryos from the park and sell them to a company that is trying to compete with Hammond. The only way Nedry can obtain these embryos is to immobilize the park by interrupting the parks normal function, so that he could sneak in and steal the embryos. This all takes place while the visitors are out in the park touring, and in the mist of a terrible storm. After Nedry has executed a virus in order to steal the embryos the storm hits, and the park power goes out. As the power goes out the visitors to the island are stuck in the middle of nowhere, with an escaped T-Rex. Everyone flees and is scattered through the park. The animals begin attacking the control building, while they are search for food. Since all the power is out there is no way to stop them, or containing them. In the hysteria a scientist , Wu, discovers that the dinosaurs have been mating, which they thought wasn't possible, because they were only cloning females, but the dinosaurs have adapted and have found a way to reproduce. They think they got the power back on so they try to put all the animals back in their holding areas. Little did they know that the whole time the park was running on auxiliary power, and once this power ran out they could not restore the main power. When all the power finally ran out the animals began attacking at full force now. Their only alternative to get the power restored is to have someone manually turn on another auxiliary power generator so they could get the main power running again. The visitors and the staff of Jurassic Park escape but with two casualties. They escape by having a helicopter pick them up. After the pick up the Costa Rican government bomb the island in order to destroy it. According to the book genetic cloning can be accomplished by obtaining just a small amount of blood. May this type of cloning be possible in real life only time will tell, and the advancements in technology it should be a thing of the future. The fact that this type of thing might be done, is slim only because of dangers of disturbing the natural flow of things. In the book the greatest marvel they discovered turned around and caused them great disaster. If man kind does try to bring back the dinosaurs will the same happen?

WTC Report essays

WTC Report essays September 11th 2001 was a tragic event that many people lived through. Many people also have some interesting stories to tell people about. This paper will tell you about some of those stories from people like firefighters, paramedics, and survivors. On September 11th terrorists hijacked four planes for a cause they believed in. They flew two planes into the World Trade Center (WTC), one into the newly renovated part of the Pentagon, and one crashed in Pennsylvania. That one crashed in Pennsylvania because the passengers of the plane tried to overthrow the hijackers. There was a battle between the passengers and the hijackers and eventually the plane crashed in Pennsylvania. At 8:46 and 9:02 a plane had hit the WTC two towers. One tower stood for 56 minutes and the other for 102 minutes. It took only 12 seconds for them to fall. There were 2,819 people who died in the attacks. 343 of them were firefighters and paramedics. 23 of them were NYPD police officers. There were 37 Port Authority police officers killed. 60 World Trade Center companies lost employees. 1,402 employees died in tower two. 614 employees died in tower one. The ratio of men to women who died is 3:1. The greatest number of people who died was from the ages of 35 to 39. Out of all the deaths only 289 bodies were found intact. There were 19,858 body parts found. 1,717 families got no remains. There were 63 babies born to a parent who died in one of the towers. After September 11th 661 firefighters retired by July 2002. 300 firefighters had to leave because of respiratory problems. Rudy Giuliani attended 200 funerals to the victims of September 11th. There were 98 fire department vehicles destroyed. Those are the losses of September 11th 2001. There were also many firefighters who survived and have amazing stories to tell. Firefighter Marcel Claes who was on engine 24 for 12 years remembers that day. He was walking up the stairs of the Nort...

Emergency Management System in UK & USA Essay Example | Topics and Well Written Essays - 750 words

Emergency Management System in UK & USA - Essay Example However, it is an area where both nations have their unique features of emergency management. For instance, UK seems to have incorporated counterterrorism with current homeland security system; whereas the US emphasis on special strategies to combat hazards emerged from terrorism. 2. Animal Emergency Management: As compared to UK, the United States pays higher priority to animal emergency management known as National Animal Health Emergency Management. NAHEMS undertakes the whole responsibilities of co-coordinating the activities of animal health emergency management with other organizations and make preparedness to encounter the emergency conditions. The responsibilities of the organization include coordination of national response infrastructure, coordinated emergency response plans and agreements, research and developments, training, education, and awareness programs (landcare.org.uk). The animal welfare act 2006 UK enacted general laws intended to ensure the protection of animals. Unlike the US system UK’s regulations mainly focus on provisions of the protection of farmed animals and domestic animals. 3. Emergency Medical Services (EMS): emergency medical service usually includes ambulance service and emergency rescue squad. It refers to ensuring urgent medical care or a higher level of healthcare to individuals with critically ill conditions. One can find considerable differences between the EMS operation systems of UK and the US. As US maintains a free healthcare market, there is no unanimous mode of operation can be found in EMS service. Although the service sector is regulated by government at federal level and more strictly at state levels, it is not solely owned by publicly-funded institutions. In addition to governmental initiatives, numerous private and profit oriented organizations also take part in the US emergency management system. They provide a wide range

Understanding Organisations and the Role of Human Resources Assignment

Understanding Organisations and the Role of Human Resources - Assignment Example This research will begin with the statement that Human Resource (HR) managers play a crucial role in the success of organisation. Human Resource Department is considered as the backbone of every organisation for the effectiveness of the employees. Organisations effectiveness and efficiency largely depends on their HR as they perform several activities regarding public relations, selection along with recruitment, and many other pivotal tasks. The role of HR is of significance as they act as a motivator for the employees and help in retaining along with attracting new talent for enhancing the operating environment. In this study, J Sainsbury's plc has been taken into consideration. Sainsbury’s initiated its venture in the year 1869 and operates globally with 161,000 employees. Sainsbury identifies its strong culture as well as values to be the core element for its success with respect to the role of effective HR managers. J Sainsbury plc is a UK based organisation and is one of the largest retailers in the country. The organisation has various areas and segments in which they deal with. The company provides its services in various aspects as the company has the largest supermarket chain to meet the requirement of the customers. The company has Sainsbury's convenience stores, online groceries facility, banks, pharmacies, energy, and mobile. Sainsbury’s plc has a large range of products in order to satisfy the needs of the people. In the current scenario, Sainsbury’s has more than 1203 supermarkets, which provides value to the customers.

Chapter12 Essay Example | Topics and Well Written Essays - 250 words

Chapter12 - Essay Example e key aim of developing educational settings, the chapter had emphasized strategies and actions plans of determining skill areas that ensure individuals with physical disabilities to become productive citizen within the nation. The significance of preparatory programs for the secondary education has been considered in this chapter as the fundamental key aspects for empowering educational stability of the youth with physical disabilities (Schloss et al., 2006). Corresponding to the pivotal role of the preparatory programs, the incorporation of providing adequate guidance to build self-determination of the students with disabilities is one of the key agents for the educational settings. The process would enable students with disabilities to strengthen their belief for establishing and achieving their educational goals. The process of creating self-determination would further facilitate the students with disabilities to make effective choices along with decision making skills to improve quality of life from different undue influences and interferences from the external environment. In addition to the significance of self-determination, the chapter has also provided a clear understanding about the function of assessing interests and skills of the students with disabilities that can substantially help the vocational institutions to improve the educational environment. In this context, emphasizing strategic priority of conducting curriculum bas ed vocational assessment, vocational aptitude tests along with person centered planning and career awareness instructions have also been accentuated in this chapter that can empower the vocational student to ensure better future of the students with disabilities (Schloss et al.,

Antimitotic Prodrugs Advantages And Disadvantages

Antimitotic Prodrugs Advantages And Disadvantages Abstract The intricate prodrug therapy has made possible the synthesis and identification of novel drug discovery that have significant structural modifications or intermediate derivatives which may facilitated and enhanced therapeutic parameter during in vitro and in vivo studies. Along with improved target delivery of prodrugs provides the capability to not only overcome certain limitation of antimitotic drugs, but to increases the chances to undergo clinical phase trial studies to get in to action. Development of these new prodrugs as improved alternatives gone through from significant challenges; nevertheless these potential therapies also use to analysed and give suggestion about their further development by clinical studies. Introduction Cancer is diseases in which the bodys cells become abnormal and split without control. Cancer cells may show aggression nearby tissues. They may spread through the bloodstream and lymphatic system to other parts of the body. [1, 2, 3]. Now the days there are mainly three types of treatments are in use surgery, radiation and chemotherapy. Among these, surgery and radiotherapy are to be employed for specific treating are and chemotherapy employed during the systemic treatment of metastases in local as well as regional cancer cells. Chemotherapeutic drugs can be divided in to alkylating agents, antimetabolites plant alkaloids (antimitotics), topoisomerase inhibitors, and other antitumor agents. All of these drugs affect the cell division or DNA synthesis and translation, and function in other ways. The proliferation rate is the play the key role in for the effects of these drugs thus; they are not much selective of tumours. Chemotherapy is treatment with drugs that kill cancer cells and make them less active. It is the treatment of disease by chemicals, especially by killing micro-organisms or cancerous cells. In popular usage, it refers to antineoplastic drugs used to treat cancer or the combination of these drugs into cytotoxic standardized treatment regimen. In its non-oncological use, the term may also refer to antibiotics, long time use of chemotherapy consequences natural cell deaths in the treatments of tumour [4]. Sometime these agents produce remission and re-growth which result in proliferation of cancer cells along with resistance of drugs. Although, intense researches have been conducted in the field of cancer, there are some pioneering ideas need to come in this field to decrease toxicities, physicochemical properties and therapeutic index [5]. The use of prodrug is generally established as a strategy to improve the physicochemical, biopharmaceutical or pharmacokinetic properties of pharmacologically potent agents, and thereby increase the develop ability and usefulness of a potential drug [6,7]. The aim of the prodrug establishment is to improve (i) physicochemical properties like solubility, chemical stability, taste and odour etc. (ii) selectivity; (iii) pharmacokinetic and pharmacodynamic problems and (iv) therapeutic index. Thus; by these improvements, we can overcome the formulations challenges of the drugs [8, 9]. The most of the antimitotic prodrugs developed with conjugating prodrug molecules to low to high molecular weight molecules like sugars, enzymes, vitamins, antibodies, polymers and nanoparticals. These are the carriers which transport prodrug in to tumour and drug release with conjugating the drug to the carrier through a spacer that include particular point which make the specific targeting of the drug. These carriers are very complicated in the structure and demand very hard work to make carries linked prodrugs. Hetrogenecity, biodistribution, expression of multidrug resistance, interstitial pressure and amount of the drug reaching to the target site, are the problems which make the task more difficult. Along with that targeting properties will preserved or not with structural changes are major problems in the formulation of carrier liked prodrug molecules. Here I provide an overview of recent developments in targeted antimitotic prodrug and conjugate design. These are examples which, illustrating the salient features of different targeting strategies. I have focused on prodrug and conjugate examples in priclinical trials or advanced preclinical studies with advantages and disadvantages associated to each strategy are also discussed. Antimitotics In the process of mitosis eukaryotic cell isolate the chromosome in its cell nucleus into two the same sets which are divided in two nuclei. In cancer the single cell start converts from normal cell to cancerous cells by the process of mitosis. The mitosis inhibitors contain certain different cancer drugs. They are different in mechanism of action from the other classes of cancer drugs [12]. They mainly interfere with cell proliferation of cell rather than alter DNA structure and function. Mitosis includes DNA replication which divides the cells in to two new cells. Spindle fibers separate newly replicates chromosomes and convert them in to two forming cells. The fibres which are produce microtubules which fix with the replicated chromosomes. Now chromosomes pull one of this copy to each side of the cell which includes spindle fibers, without that cell cannot divide. Antimitotics inhibit this earlier uncertain spindle function during cell cycle. Spindle fibers form of long chains of smaller subunit of tubuline protein. In the process of polymerisation tubuline subunits can add to microtubule. Some types of antimitotics stop the process of forming of tubuline monomers which inhibits the microtubule. In this process they arrest movement of chromosomes as well as spindle tubule [13]. Examples of mitotic inhibitors include Taxanes, paclitaxel (Taxol) and docetaxel (Taxotere), Epothilones like ixabepilone (Ixempra), and Vinca alkaloids: vinblastine (Velban), vincristine (Oncovin), and vinorelbine (Navelbine), estramustine (Emcyt) and Colchicines. Vinca alkaloids and colchicines are those who have more over same mechanism of action. Vinblastine inhibiting the formation spindle fibers which are responsible for position of chromosome and the separation of the chromosomes during anaphase. It also inhibits the formation of microtubules which are responsible for the formation of cell division. Vinca alkaloids have many side effects like others [14]. Vincristine also binds to the tubuline monomers and arrests the formation of spindle microtubules. As result of this, it blocks the movements of chromosome during cell division. Speficity is the major problem with vincristine because it also affects the healthy cells with cancer cells during cell division. Vindesine is another Vinca alkaloid who binds to the microtubules. It has target specificity problem which makes them less potent [15]. Texel is natural antimitotic drug and different in mechanism of action from Vinca alkaloids. Paclitaxal and docetaxel are the two important analogues . Paclitaxel inhibits microtubuline assembly rather than monomers. It binds to microtubules and prevent this breakdown because these two processes, polymerisation and breakdown, both are requiring for movement of replicated chromosomes. The prevention of chromosomes breakdown inhibits them to move to opposite direction of dividing cells. Reduction in bone marrow function which may result in anaemia, blood in stools or black stools, fast or irregular heart beat, are common side effects associated with paclitaxel [16]. Docetaxel has same mechanism of action as paclitaxel but if the drug is give with combination it will cause major side effects than paclitaxel [17]. Epothilones is microtubule function inhibitor. It binds to beta-tubuline subunit on microtubules and preventing polymerization during cell division and eventually causes cell death. Mainly peripheral neuropathy, mylosuppersion with white blood cells and hypersensitivity reactions are the side effects which cause by Epothilo nes [18]. Colchicines are antimitotics which have same mechanism of action as Vinca alkaloids. It also binds to tubuline and inhibits polymerization of microtubules. Tubuline availability is necessary for mitosis process and colchicines are inhibiting these tubules as spindle poison. Cancer cell have nature to proliferate most and this make them more susceptible to Colchicines drugs [19]. These are natural anitimitotics and their analogues. Their mechanism of action is mainly on tubuline and sometime called antitubuline agents. But they have their own challenges like insolubility, bioavability, pharmacokinetic and pharmacodynemics, and toxicities problems. Tubuline plays a key role in their effects to bind mitosis but to overcome these challenges, proteins which are involve in the mitosis, are founded. They are presently under process to develop the capacity of clinical efficacy that those drugs have established [20]. Present scenario in antimitotics drug development (Specific druggable protein targets) The targeted proteins with specific function of new generation of anti mitotics are identified with molecularly targeted drug discovery. These new agents play important role in the unique way to provide the significant effects, which take beyond the certain limitations of drugs as well as extend the scope of their clinical efficacy of current antitubuline drugs. Although, they are facing some considerable challenges, but molecular mechanism of action of mitotic-checkpoint plays important role in mitosis [21]. Antitubuline drugs have complex chemical structure and are complicated to isolate and synthesised from their natural sources. Neurotoxicity and insolubities are the major problems with Vinca alkaloids and Taxanes. They also interfere in function of microtubules in axons, which provoke the neuronal vesicle motility. The non-structural components of mitosis as potential drug targets are one of the solution for therapy. They have unique effects in morphological stages during the mi tosis which is bring mitotic Kinesins, Aurora kinases and polo-like kinases (PLKs), as druggable protein target classes [22]. Targeting these proteins is well known as mitotics kinesin, kinesin spindle protein (KSP) are requires for the proliferation from prophase to prometaphase and Centromeric protein E (CENPE) is required during prometaphase to metaphase and also have effects in mitotic checkpoint [23, 24]. These protein targets are only finds in dividing cells so non-dividing cells are not effected. This showed that, this kind of target inhibition have potential and improved therapeutic index compare to tubuline target anti mitotic drugs. Although, proteins inhibitors might not enough effects on both the mitotic spindle and cytoskeleton but they have some significant role out side the mitosis. Moreover, to support these new agents, the role played by them in the mitosis, cause target inhibition to be connected with tumour growth inhibition. By the using pharmacodynemic marker, significant effective dose during drug development founded. These doses were affected instead of maximally tolerated dose, might also caused improved therapeutics index. The mechanism of action of these agents by which they inhibits tumour cells undergo cell death was not properly defined but they have many positive effects on these proteins. Activation of caspace 3 (significant effectors) has been identified in studies of protein target drugs, along with that mitotic catastrophe has also been founded [25, 26, 27]. Actually, catastrophe is cell death occurs from metaphase of mitosis against the drugs that produce DNA damage because of in this stage the caspace 2 is involved rather than caspase 3 which produces many morphological and therapeutic aspects of cell death. On the other hand, mitotic check point as effectors of cell death against protein inhibitors was contentious. It was suggested that KSP inhibitors needed mitotic checkpoint. In contrast to that, role of checkpoint studies involved that; this signalling might cause cell death with mitotic damage [28, 29, 30]. This mechanism might supported by Aurora B inhibitors [31]. Eventually, the mechanism of action of these new protein inhibitors became more understandable that, they are more involved in killing cell by unique mechanism but also, different genetic alterations, which may produce during cancer, play the important role during inhibition by these agents. Although, this studies is unfinished so its hard to get these new agent in action because they needed further more researches. KSP Inhibitors: Ispinesib was first KSP inhibitor and studied in clinic to check the therapeutic effects. Small molecules of KSP ATPase were targeting by this drug but it was not involved in effecting ATP and ADP. In terms of specificity, it was 40,000 times more selective as compare to other kinesins. Firstly it was studied intravenously and results founded that during different number of days, the cumulative dose delivery was same and dose limiting toxicity on both occasion was neutropenia as well as haematopoietic lineages, along with that nausea, vomiting and diarrhoea also observed. Raise in the dose also increases the amounts of phosphor-histones-H3 in tumour which involved inhibition of proliferation of tumour cells with dose. As consequence, the pharmacodynamic activities also increased. In earlier, the renal cell, hepatocellular and colorectal cancers are not responding to anti tubuline agents, but this KSP inhibitor extend the time duration of stability for more than 6 months. This agent a lso needed following treatments of natural anti tubuline agents [32]. The next KSP ATPase inhibitor is same to Ispinesib, and during clinical evaluation it came from the chemical synthesis [33]. It has more efficacious than first one. During the studies it is connected with dose limiting toxicities that is neutropenia and hyperbilirubinaemia [34, 35]. For cholangiocarcinoma, it gives some positive effect and two more cancers extend as stable diseases for more than six months. Third potent KSP inhibitor is MK-0731. It is more selective about more than 20,000 fold and associated with increased activity of hepatic transaminases and neutropenia [36]. Finally, clinical experience of KSP inhibitors showed that these agents associated with common dose limiting toxicities like neutropenia, increased activity of hepatic transaminases which are also observed with tubulin inhibitors. Although, some of toxicities like alopecia, mucositis and neuropathy, are not often seen. Nausea and vomiting have seen uncommonly with these protein targeting inhibitors. AURORA and PLK inhibitors One of the potent drug called as VX-680 also know as MK0457 as ATP competitive inhibits Aurora A, B and C to inhibit the cell differentiation in cell culture [37]. Its mechanism of action is to inhibit the FMS-related tyrosine kinase 3 and imatinib-resistant mutants forms of Abelson tyrosine (ABL) kinase. Imatinib and dasatinib are the resistant to those agents. During the studies, cancer cell from different patients, were tested against intravenous infusions. As results, neutropenia was mostly observed dose limiting toxicity and when the dose increased the some pharmacodynemic effects in skin was also observed. To evaluate that, phospho-histone-H3, Ki67 (antigen) and cycline B1 expressions are being checked before and after these studies. In the skin biopsies, there was no strong evidence observed, which showed the mitotic arrest or decrease in cell proliferation in the skin, during clinical studies. There was strong proof about the effects on cell proliferation which are haematopoi etic, but it was not case with skin biopsies. Mitotic inhibition, aneuploidy, was expected from the pan-Aurora but only delay in the mitotic progression observed during studies. Moreover, these agents inhibit the Aurora B and decrease the PHH3 levels when other anti-mitotic agent increases this biomarker. To overcome this limitation, the assays procedures developed which are capable to find out the decrease in the level of PHH3. Skin was not responding to these drugs. Extended stable disease for more than 6 months observed [21]. Another ATP-competitive Aurora B inhibitor is AZD1152 with significant IC50 cellular proliferation. This inhibitor evaluated in two schedules. In the both schedules, neutropenia observed as dose limiting toxicity for intravenous infusion. Moreover, next assessments reached in phase I and II studies for cancer like leukaemia [38]. BI 2536 is first ATP-competitive inhibitor of PLK1. There were three different partitions to evaluate this small molecule inhibitor. Every partition was evaluated by intravenous infusion and as result of that, same toxicity and dose delivery were obtained. Thrombocytopenia and neitropaenia were major dose limiting toxicities in every partition [39]. The second ATP non-competitive inhibitor of PLK1 is ON 01910. It may support PLK, to bind the substrates. It is currently under trail for two different doses because it has low potency to FLT1 and platelet derived growth factor receptor (PDGFR). Increased activity of hepatic enzymes, anaemia, leucopoenia and gastrointestinal symptoms, are the adverse effects with this inhibitor [40]. All over, neutropaenia without significant neuropathy was major dose limiting toxicity with these inhibitors. Challenges and Developments in New Antimtotic Drugs Although, these novel antimitotic drugs have very significant role in inhibition of mitosis, they are facing many problems during their developments. Their appropriate ways, potential to reduce toxicities, activities, safety profile, and efficacy are some promising questions are yet to be solved. These agents have reduced risk of neurotoxicity, which is proved in clinic, but they also have dose limiting toxicities like neutropenia with relative sparing of the other haematopoietic lineages. So it will be difficult to tell yet that they have potential [41]. Another challenge was that, there was no clear perceptive between inhibition of respective mitotic target and cell death. Because they have mechanism of action is to arrest mitosis but whether this mitosis arrest initiate by activating by mitotic checkpoint or it is followed by mitotic slippage for further cell death. To identify the patients who are best responding to these agents is also a challenge in developments in theses agents. In addition to that, during clinical development, it is difficult to develop surrogate tissue to check the pharmacodynemic responses of these drugs because targets of these agent, was absent in most of them [42]. Along with pharmacodynemic effects, duration of such effect both is also crucial determinants for apoptosis. Therapeutic window can be calculated by evaluation of tumour markers at maximum tolerated dose (MTD) or below the MTD if possible but this might be achieved by incorporation of serial tumour biopsies was uniquely challenging. In addition to, which schedules would be sufficiently discover pharmacodynemic and pharmacokinetic data was difficult [43]. Considerable steps have already come in to view, to overcome these limitations and evade toxic side effects, produced by these agents. Such steps make two different types of practices; they are prodrugs and drug targeting methods. During these practices both methods led to increase some of biochemical properties along with pharmacokinetic and pharmacodynemic effects. Prodrug Prodrugs are chemically modified versions of pharmacologically active agents that must undergo transformation in vivo to release the active drug. The prodrug is administered in an inactive or significantly less active form. The use of prodrugs is generally established as a strategy to improve the physicochemical, biopharma-ceutical or pharmacokinetic properties of pharmacologically potent agents, and thereby increase the develop ability and usefulness of a potential drug [6]. Antimitotic Prodrugs which are in Use or Developing The following are the antimitotic prodrugs which try to develop to overcome these limitation associated with specific antimitotic drugs like Vinca alkaloids, Texans, Cochicines and phodopyllotoxins. A) Hydrolytically Activated Paclitaxel Prodrug Paclitaxel is well using in diseases like ovarian cancer, breast cancer and lung cancer but it has limitation like low water solubility, less effective, drug resistance and some effects. At high dose it produces hypersensitive reactions, hematologic toxicity, and neurotoxicity. It also limited by granulocyte colony-stimulating factors dependent neutropenia. It has dose dependent neurotoxicity expressed by loss of sensation [44]. Adapt from [44] By masking position7 hydroxyl group of paclitaxel with hydrophilic side chain (*) and resulted 7-(2, 3-dihydroxypropyl carbonoxy) paclitaxel is biologically inert and is activated at low pH conditions by hydrolytic cleavage of the carbamate linkage, obtaining active paclitaxel, dihydroxy propanol, and CO2 [44]. Following are the results obtained by analysing paclitaxel prodrug. Figure, (A) Figure, (B) Table 1, Figure A and Figure B, Adapt from [44]. Table 1 is hydrolytic activation of paclitaxel prodrug in vivo, indicating decrease in prodrug and increase in active drug. Figure (A), for conversion to active paclitaxel in vivo, indicating peak plasma concentrations were observed at 3 hours for paclitaxel prodrug (P1) and at 6 hours for active paclitaxel (P2), for 1 patient. Figure (B), for activation of paclitaxel in vivo, demonstrates the slow-release mechanism in vivo, for 5 pateints [44]. B) First enzymatically activated Taxotere Prodrugs Designed for ADEPT (Antibody Directed Enzyme Prodrug Therapy) and PMT (Prodrug Mono Therapy) Paclitaxel and its semi synthetic analogue docetaxel is essential drugs in the treatment of cancer as antimitotic drugs. There is slight difference between them is substitution at 3- nitrogen on the side chain and the 10-posititon of the taxoid core. They have high potency to solid tumour but they have number of undesirable side effects and poorer water solubility and also with detergent they initiate hypersensitivity reaction on body. These drugs delivery have evaluated on enzymatic hydrolysis in ADEPT (Antibody Directed Enzyme Prodrug Therapy) and PMT (Prodrug Mono Therapy).The two docetaxel prodrugs in figure A have synthesised with glucuronic moiety is linked to a double spacer. Para hydroxyl bezyle alcohol connected to diamer tether through a carbamate linkage in this spacer. This complex was shown to be more potent and labrets drugs in the presence of ÃŽÂ ²-Dglucuronidase enzyme in ADPET and PMT therapy [45]. Figure A, structure of scheme 2 and scheme 3 (Prodrug 4), scheme 2 and scheme 4 (Prodrug 5) and Prodrug 3 Adapt from [45] Following are the results by the comparison of these two drugs. Both of prodrugs have 24 hr-run of stability and there was no release from the prodrug during this time. Table 1 showed that these two prodrugs have compatible IC 50 values for the ADEPT and PMT strategy. Figure A and figure B showed that, during HPLC detection, prodrug level decreased until finished and spacer and parent drug, docetaxel, reached at area of stability [45]. Table 1, measured for L1210 cell lines were (HPLC): Prodrug, Scheme 2 and scheme 3 : 4.86 uM Docetaxel : 14. 4 uM Spacer: 75.3uM Prodrug, Scheme 2 and scheme 4: 2.69 uM Spacer:45.8uM Figure A, Comparison of the disappearance of the three prodrugs. Figure B, Enzymatic cleavage of prodrug 5 Figure 2, Scheme 2 and Scheme 4. Table 1, Figure A and Figure B adapt from [45]. C) Zyn-Linked colchicines: Controlled-release lipophilic prodrugs With enhanced antitumor efficacy Zyn-linked drug have rapid binding property to cell membrane. These Zyn-linkers prolong their binding and preservation in tissues, make sense to produce Zyn-linkers conjugates those who have better local delivery of therapeutics. Colchicine has chosen for these studies because this drug and its analogues are still under examination. Five Zyn linked colchicine analogues with either cleavable hydrazone or imine bonds, have synthesised and evaluated their stability ,cytotoxicity and antitumour activity [46]. Fig.1. Structures of colchicine and modifications to form the analogues for Zyn-Linking are shown. Fig. 2.Structures of the Zyn-Linkers modified for attachment of the colchicine analogues. Fig.3. Structures of Zyn-Linker conjugates are shown with the bonds subject to hydrolysis indicated by an arrow: (a) hydrazones conjugates linked at the B-ring of the colchincine moiety, (b) imine conjugate, and (c) hydrazones conjugate linked at the A ring of the colchicine moiety. Figure 1, 2 and 3, adapt from [46] Following are the results for their relationship among different properties. Table 1 Table2 Table3 Table 1, 2 and 3, adapt from [46] Table 1 showed that, ZYN 162 and PKH 158 at pH 7.2, are two potential products and out of them one is expected and one is unidentified products. Table 2 showed that, 80% to less than 1%, was range of therapeutic and unhydrolysed conjugated, was inactive. Zyn-linkers had no antimitotic activity; on the other hand, drug or Zyn-linked drugs were active. Table 3 showed that, with 4-formayl group thiocolchicine have reduced their toxicities and enhanced therapeutic activity [46]. D) Preparation, characterization, cytotoxicity and pharmacokinetics Of liposome containing water-soluble prodrugs of paclitaxel Paclitaxel have antimitotic effect against the various cancers like breast cancer, ovarian cancer, head and neck cancers. Due to its aqueous insolubility, it was dissolving in the mixture of 50 % Ethanol and 50 % Cremopher EL (caster oil). Neurotoxicity and hypersensitivity are side effects of this Cremopher. So to reduce this side effect and to enhance the drug entrapment in liposome with better aqueous solubility, three prodrugs and prodrugs liposome formulations have synthesised and evaluated their pharmacokinetic parameter, stability and antitumor activity with parent drug [47]. Following are the results obtained during comparison in stability, cytitoxicity and pharmacokinetic property of drug, prodrugs and their prodrug liposome. 1) Stability Table1 Table 2 Figure 1, 2 and 3, Table 1 and 2, adapt from [47] Figure 2 and 3 showed that, by the changing the property like diameter, membrane fluidity and charge, liposome containing 2-mPEG-paclitaxel composed of PC-PG-CHOL 9:1:5 showed better stability more than 2 months and good entrapment ability. Table 1 and 2 showed that, in vitro cytotoxic effects of liposome containing compound 3 and 4 on two cell line, HT-29 and MeWo, maintained, but rapidly hydrolysed and giving free parent drugs, while liposome loaded paclitaxel-2succinyl had more resistance to hydrolysed. 2-PEG-paclitaxel also had ability to make difference in pharmacokinetic parameters as compare to free drug [47]. D) Synthesis and evaluation of water-soluble docetaxel prodrugs- Docetaxel esters of malic acid. Paclitaxel and docetaxel are semi synthetic analogues widely used for various cancers. But water solubility is major limitation for these drug and to come over from this limitation, at C20, C7 -or/and C10 position several research group introduced solubilising moieties [48]. Figure A Figure A, table 1 and table 2, adapt from [48] Figure A, table 1 and table 2 showed that, 20-DLmalyl docetaxel sodium salt 3a come out with excellent water solubility, more active than docetaxel in vitro and antitumor activity in vivo [48]. E) Synthesis of Water Soluble Prodrugs of the Cytotoxic Agent Combertastatin A4 Combertastatin A4 has structure similar to colchicine. It is an inhibitor of tubulin polymerisation to stop proliferation of cells. Although, this drug has potential for antimitotic activity, it is soluble in the few pharmaceutically accepted solvents. Synthesis of water soluble glycosides of combertastatin A4, have conducted by make modification by hydroxyl function. To increase the yield, they have reversed the components of the Witting reaction [49]. Adapt from [49] The ammonium salt have prepared and converted into potassium salt to make crystal form. This ammonium salt was more stable in buffer solution and degraded slowly in plasma at 37 C when incubated with acid phosphates and alkaline phosphatise [49]. F) Prodrugs of 40-Demethyl-4-deoxypodophyllotoxin: Synthesis and Evaluation of the Antitumor Activity 4-Deoxypodophyllotoxin (DPT) and 4-demethyl-4-deoxypodophyllotoxin (DDPT) have comparable in vitro potency against different cell lines but free hydroxyl group at 4 position in structure of DDPT loss its in vivo antitumor activity against BDF1/3LL model. Replacing this free group by bioreversible functionality might improve in vivo activity. For that series of prodrugs have synthesised and evaluated their cytotoxic and antitumor activities [50]. Following are the results obtained during studies. Adapt from [50]. Table showed that 10 and 11 derivatives were properly transferred in to parent drug 2 but weak in vivo activity and 6 derivative showed IR of 95% of antitumor activity. The carbamates and carbonates of two compounds, 6 and 9, showed potent antitumor activity, might be by intermolecular cyclic rearrangements of hydroxyl side chain. Moreover, amino acid prodrugs, 12 to 17, demonstrated better water solubility and potent antitumor activity [50]. Discussion Presently the antimitotics prodrugs are novel compounds and hold many promises and may have abilities to improve the drawbacks of anti tubuline or specific protein inhibitors, which are regulating the cell cycle, demonstrated by clinical data. With observations to clinical activity, it is too premature to tell for most of the agents in development. There are number of prodrugs have been developing and some have evaluated in laboratory. Antimitotic prodrugs may improve limitations of these drugs during in vitro and in vivo studies but there are still need more information about clinical phase trails by using number of patients, to these prodrugs. In particular, hydrolytically activated paclitaxel prodrug has decreases toxicity in vivo and produced better responses in patients with end stage in cancer. Serum half- life also dramatically increased with maximum plasma concentration, in vivo, but more studies require about responses in phase III trails, as it was evaluated in 10 patients. Moreover, information needed about, high concentration expose to tumour tissue for critical time, as significant G2M phase arrest is primary mechanism of action. First prodrugs of docetaxel have synthesised for the ADPET (Antibody Directed Enzyme Prodrug Therapy) and PMT (Prodrug Mono Therapy) strategies. Spacer have nitro group on the aromatic ring. In the hydrogenesis step it could be preserved which is not seen in the previous paclitaxel prodrugs. This nitro and amino groups containing prodrugs have expressed good kinetics and enzymatic hydrolysis in particular cell line, but more information needed about self immolative spacer for its effects on the paclitaxel on various cell lines. This issue need more clarification prior to clinical trails in malignancy models. Four conjugates of Zyn-linked colchicine have hydro linkage, imine bond in spacer arms, colchicines moiet

anthropic principle :: essays research papers

The Anthropic Principle In the early 1970s, Brandon Carter stated what he called "the anthropic principle": that what we can expect to observe "must be restricted by the conditions necessary for our presence as observers" (Leslie ed. 1990). Carter’s word "anthropic" was intended as applying to intelligent beings in general. The "weak" version of his principle covered the spatiotemporal districts in which observers found themselves, while its "strong" version covered their universes, but the distinction between spatiotemporal districts and universes, and hence between the weak principle and the strong, could not always be made firmly: one writer’s "universe" could sometimes be another’s "gigantic district". Moreover, the necessity involved was never -- not even in the case of the "strong anthropic principle" -- a matter of saying that some factor, for instance God, had made our universe utterly fated to be in telligent-life-permitting, let alone intelligent-life-containing. However, all these points have often been misunderstood and, at least when it comes to stating what words mean, errors regularly repeated can cease to be errors. Has Carter therefore lost all right to determine what "anthropic principle" and "strong anthropic principle" really mean? No, he has not, for his suggestion that observership’s prerequisites might set up observational selection effects is of such importance. Remember, it could throw light on any observed fine tuning without introducing God. Everything is thrust into confusion when people say that belief in God "is supported by the anthropic principle", meaning simply that they believe in fine tuning and think God can explain it. As enunciated by Carter , the anthropic principle does not so much as mention fine tuning. Being aware of possible "anthropic" observational selection effects can encourage one set of expectations, and belief in God another set. If suspecting that Carter’s anthropic principle has practical importance, you will be readier to believe (i) that there exist multiple universes and (ii) that their characteristics have been settled randomly, some mechanism such as cosmic inflation ensuring that all was settled in the same fashion throughout the region visible to our telescopes. True, the believer in God can accept these things too, yet he or she may feel far less pressure to accept them. Even if there existed only a single universe, God could have fine tuned it in ways that encouraged intelligent life to evolve. A possible argument for preferring the God hypothesis runs as follows. A physical force strength or elementary particle mass can often seem to have required tuning to such and such a numerical value, plus or minus very little, for several different reasons.