Why has Richard Wagner been a controversial composer even today Essays

Why has Richard Wagner been a disputable writer even today Essays Why has Richard Wagner been a disputable writer even today Essay Why has Richard Wagner been a disputable writer even today Essay in which the symphony was not, at this point a basic backup to the artists, however a necessary piece of the activity. Wagner made the music persistent, not at all like the past propensity to make a show as an assortment of discrete arias and outfits which could be performed independently . He utilized an unpredictable arrangement of what are called Leitmotifs, or melodic thoughts which represent characters , things or thoughts in the show. With Wagner, harmonies turned out to be more mind boggling than any time in recent memory, and his progressive utilization of this component affected authors all over, and prompted the music of the twentieth century. As I previously referenced, Wagner is the most questionable writer of nineteenth century. He partitions individuals as no other author did it previously. Many individuals and melodic pundits discover his work superb, however there are a great deal of other people who cannot stand his music, as a result of his thoughts, for the most part political assessments in the reality. Indeed, even a century back, numerous pundits and arrangers thought his music was dreadful clamor, with the most clamorous harmonies, yet others perceived its enormity. Wagners shows, compositions, his legislative issues, convictions and irregular way of life made him a questionable figure during his lifetime. The discussion about his thoughts and their translation, especially in Germany during the twentieth century, kept on making him strategically and socially questionable such that other incredible arrangers are definitely not. The greatest issue is produced by Wagners remarks on Jews, which keep on impacting how his functions are respected, and by the expositions he composed on the idea of race from 1850 onwards, and their putative effect on the counter Semitism of Adolf Hitler. In a portion of his expositions, Wagner assaults Jewish peers, particularly Felix Mendelssohn, and blamed Jews for being an unsafe and outsider component in German culture. Wagner expressed the German individuals were repulsed by their outsider appearance and conduct. He contended that since Jews had no association with the German soul, Jewish performers were just equipped for creating shallow and counterfeit music. They in this way made music to accomplish notoriety and, in this way, monetary achievement, instead of making certified show-stoppers. That is the reason, Wagner was the Hitlers most loved arranger and he made his name an image of the Nazis. Because of his fascination, Hitler embraced numerous pieces of Wagners thought and utilized this as purposeful publicity that would impact World War II. Subsequently Wagners dramas can't be found in the cutting edge province of Israel in spite of the fact that his works have been communicated on government-possessed TV and radio. Right up 'til the present time, the individuals who endeavor arranging open exhibitions are ended by fights, including fights from Holocaust survivors. As an extraordinary model, I have viewed, the incredible from the filmmaking perspective, Triumph of the Will the most sensational at any point made promulgation film by Leni Riefenstahl, which narratives the 1934 Nazi Party Congress in Nuremberg. The film opens with shots of the mists over the city, and afterward travels through the mists to coast over the gathering masses beneath, with the expectation of depicting excellence and magnificence of the scene. The shadow of Hitlers plane is obvious as it ignores the small figures walking underneath, joined by music from Richard Wagners Die Meistersinger von Ni rnberg, which gradually transforms into the Horst-Wessel-Lied. Among Wagners thoughts was that the show be a continuous tune, likewise accentuating dramatization as a point of convergence. To Wagner, the drama was a definitive mix of the considerable number of expressions. Spending numerous years estranged abroad, he went for significant stretches without hearing the exhibition of his own works. It is exceedingly hard for us of the current age to do equity to Wagner, or to show up at any last and fair ends concerning the changeless estimation of his monstrous accomplishment. As an end, today Wagner is not, at this point an image of Nationalism and Nazism, as he was toward the start of the contention. Like Lili Eylon in her article Wagner Controversy says: The inquiry isn't whether Wagners music is of high or low quality, nor is the contention about how profound situated was his enemy of Semitism extremely important. There is no uncertainty that there have been different arrangers who were no less enemy of Semitic. While it can't be kept up that Wagner was legitimately liable for German National Socialism, there is no uncertainty that he was a ground-breaking image in the Nazi time, and his music held a solitary significance in the Nazi mind. For the individuals who endure the Holocaust, Wagners music is awful token of the repulsiveness those individuals have experienced. For them music must be isolated from the legislative issues, however tragically Wagner was the author, who really consolidated them and turned into the arranger of music and race.

Foreshadowing and Irony in “Sweat” by Zora Neale Hurston

The short story â€Å"Sweat,† by Zora Neale Hurston, appears to embody the encapsulation of an awful marriage. Hurston utilizes hinting and incongruity to exhibit the broke down connection between the oppressive spouse and the constant wife. All through the story, it becomes clear that the spouse doesn't oblige by the aphorism, â€Å"Do unto others as you would have them do unto you. † Hurston’s utilization of incongruity and anticipating uncovers the way that â€Å"the positive attitude prevail† and Sykes will at last get what he merits. From the earliest starting point, the peruser sees the mental and obnoxious attack that Sykes puts on Delia. It was a Sunday and Delia chose to excel on her work for the week by isolating heaps of garments by shading. Dread at that point happened upon her when â€Å"†¦something long, round, limp, and dark fell upon her shoulder and crawled to the floor next to her† (355). Sykes’ bull whip, confused with a snake, conjures â€Å"great terror† (355) and extraordinary dread in Delia, anticipating an occasion that is to come later on. It likewise shows the far off connection among Sykes and Delia. With full information on Delia’s dread of snakes, Sykes keeps on frequenting her with them all through the story. While Delia tumbles to the abuse of her better half, Sykes nearly submits these goes about as torment. In light of Hurston’s solid utilization of incongruity, it is obvious that one day Delia will win and a piece of information to Sykes’ destiny is given: that one day he will be spooky by a snake too. Delia is clearly the provider of the family and endeavors to help both herself and Sykes. Shockingly, Sykes underestimates this by exploiting the free lodging while at the same time setting aside his seldom earned cash to spend on other ladies. Completely mindful of this, Delia makes reference to that â€Å"†¦whatever goes over the Devil’s back is got the opportunity to go under his midsection. At some point or ruther, Syke, similar to every other person, is gointer procure his sowing† (357). The utilization of incongruity here exhibited that â€Å"what goes around, comes around† and indeed suggests Sykes’ destiny. A lot more signs all through the story appear to insinuate Sykes’ demise. Different men in the town appear to affront Sykes and even propose that he should bite the dust. While Delia began to convey the perfect clothing around one ay, the men discussed how Delia is unreasonably useful for Sykes and that she merits better, They likewise scorn Sykes for going around with an appalling and husky lady, at last undermining his persevering spouse. At long last, one man says, â€Å"Syke Jones ain’t wuth de shot an’ powder hit would tek tuh murder ‘em. Not to hu h he ain’t† (357) while another man includes, â€Å"†¦an’ we oughter execute ‘im† (358). It appears Hurston depicts this threatening vibe toward repeat to the peruser that Sykes will succumb to a merited passing. Maybe the most significant occasion in the story happens when Sykes brings home an enormous six-foot living snake. Dread indeed defeats Delia and she argues, â€Å"Syke! Syke, mah Gawd! You take dat rattler ‘way from heah! You gottuh. Goodness, Jesus, have mussy† (360). Sykes, then again, remains in entertainment as though he wants to see Delia mentally mishandled. His arrogance unwinds as he acts like he is strong and like anybody and anything ought to and will conform to him. With respect to the huge snake, Sykes brags, â€Å"†¦He wouldn’t nibble me cause Ah knows how tuh handel ‘im† (360). He tries to ingrain dread into Delia by advising her to be cautious in light of the fact that the snake would have no issue coming after her. Hurston likewise has Sykes depict his own passing. In this equivalent scene, Sykes’ answer to Delia’s solicitation of disposing of the snake is, â€Å"Ah ain’t got the chance to do nuthin’ uh de kin’ †truth is Ah ain’t got tuh do nothin’ however die† (360). This announcement just implies that Sykes won't tune in to Delia at whenever and appreciates tormenting her in any capacity conceivable. He concedes that he would prefer to pass on than give Delia the joy of control at any second. This situation is maybe the most unexpected on the grounds that it is this equivalent snake that takes Sykes’ life for the last time.

The Benefits of Writing An Essay on Womens Issues

The Benefits of Writing An Essay on Women's IssuesOne of the main obstacles that most students face in writing an essay is prejudice against females. Many students are made to feel uncomfortable when they attempt to write an essay on female issues. For this reason, there are many sample essays on the Internet that can help you overcome this problem. The following article discusses some of the different essays that are available and their relevance to writing an essay on women's issues.'Women's Experience' essay samples deal with topics of love, romance, pregnancy, education, and business. Some of the topics are discussed in a technical manner, while others deal with the emotional realities of motherhood. This topic analysis is done in an academic manner, which provides the student with an educational understanding of these issues.These article samples are intended to be informational. They provide information about some of the most relevant topics for the female perspective. When stu dents read the essays, they will have a better understanding of the subjects being discussed. The example essays give the reader an idea of what is expected when writing an essay on a specific subject. The examples allow students to learn what some of the usual reasons are for not writing an essay on a certain topic.There are two main reasons for not writing an essay on a particular topic. One reason is due to the 'writer's block' that often happens when the student has a huge quantity of homework to complete in a short period of time. In addition, students feel intimidated by some of the topics that may be discussed in an essay.Another reason for not writing an essay on a difficult topic is because it is difficult to prepare and edit an essay on a subject that is controversial. There is often a need to justify the material being presented in the essay, and this is usually something that does not exist when dealing with academic articles. This is a common problem that students shoul d not let distract them from completing their assignments. When a topic is controversial, it is important to consider how students will react to the information being presented in the essay.In addition to the sample essays listed above, there are many other resources that are designed to help students become more knowledgeable in writing an essay on a certain topic. The best way to find these resources is to look online. There are many websites that provide information about the same topic as that of the sample essay on the Internet.Students who are unable to write an essay on a controversial topic, or those who have difficulty getting started writing an essay due to this reason should be provided with adequate assistance and encouragement. It is very important for students to be willing to seek out help in order to become more confident when writing. This way, they will be able to write an essay on a topic that they are comfortable with.By following the steps listed above, students will have no trouble writing special essays. The ability to write essays on sensitive topics will increase students' confidence, and their grades will also improve. In addition, students will be able to interact with others who are in the same situation as they are, which can make the entire experience much more pleasant.

Racial Discrimination In To Kill A Mockingbird Analysis

Racial discrimination in To Kill a Mockingbird To Kill a Mockingbird by Harper Lee, published in July 11, 1960, shows the discrimination throughout the small town of Maycomb. Scout, the daughter of a white lawyer named Atticus, tells what she saw while she was growing up. Harper Lee uses foreshadowing throughout the entire story. When Atticus defends Tom Robinson in an alleged rape case. The people of Maycomb automatically start calling him, Scout, and Jem â€Å"nigger-lovers† for defending a black man. Mr.Raymond is disliked because he lives with a black woman and their kids are mixed. Jem tells Scout in chapter 16, â€Å"..but around here once you have a drop of negro blood, that makes you all black.†(page 81) In their society a white male or†¦show more content†¦Lula, a black woman at Calpurnia’s church, doesnt like when Cal brings the kids to her church. â€Å"Lula stopped, but she said, You aint got no business bringin white chillun here—they got their church, we got ourn. It is our chur ch, aint it, Miss Cal? (158-159) Lula believes that if blacks are treated differently she should also treat the whites badly too, reverse racism. Reverend Sykes and Cal both tell her to cut it out because Jem and Scout shouldn’t hear nor listen to her. Reverend Sykes welcomed the kids into the church along with everybody in the church. That was one of the few times where the kids witness racism first-hand. When Atticus is giving his testimony for Tom he says, â€Å"She was white, and she tempted a Negro. She did something that in our society is unspeakable: she kissed a black man. Not an old Uncle, but a strong young Negro man. No code mattered to her before she broke it, but it came crashing down on her afterwards.(chapter 20.)†. The code Atticus refers to, deals with taking advantage of the lower class. When Mayella said that she ways taking advantage of and hurt, it was really the other way around. Her father beat her after being caught kissing Tom. Mayella doesn’t want to tell the entire town that her father abuses her because she knows what may happen. When Tim is on the stand, he says he felt sorry for Mayella. The lawyer defending herShow MoreRelatedEffects Of Racial Discrimination In To Kill A Mockingbird1526 Words   |  7 PagesRacial discrimination is when you treat someone differently based on the color of their skin or when you think different races exist in the world. Racial discrimination comes in two different forms extrinsic and intrinsic. Extrinsic is when you believe that a certain race is bad. Intrinsic racism is when you have a specific hatred towards a certain race. To Kill a Mockingbird, a novel that shows many forms of racial discrimination that was written b y Harper Lee in the 1960’s. In To Kill a MockingbirdRead MoreRacism And Critical Disposition Of Kill A Mockingbird By Harper Lee1415 Words   |  6 PagesAn Analysis of Racism and Critical Disposition in Maycomb County Racism was a tremendous issue in Harper Lee’s To Kill a Mockingbird. It was applied throughout the novel and was increasingly used to judge others in Maycomb’s society. Racism was revealed through the novel to characters Jem, Scout, and Dill who were young children that were learning about the good and evil in the small town they lived in. Racism was a constant and significant topic. There were many aspects that contributed to racismRead MoreArgumentative Essay : Argumentative Paper 1610 Words   |  7 Pagestrue racial and social equality. There are many realistic examples of the modern United States that show that the country will never achieve such goal. Indeed, one can see these events and conclude that America is not the land of the free, for other groups of people are mistreated for being of another race, or simply for being â€Å"inferior† to the eyes of society. Even some famous writings by authors prove that the U.S. will never achieve true racial and social equality. Harper Lee’s novel To Kill A MockingbirdRead MoreRacism Towards Negros : The And Worst Parts Of American Society1832 Words   |  8 Pagesfrom their enslavement, but the racism towards them didn’t disappear overnight. Racial discrimination is evident in many elements that affect health, including social status and employment because racism is one of the main barriers in our society to the attainment of health care. Employers, co-workers, and peers may favor one or more people over African Americans because of their skin color. In To Kill a Mockingbird (1960), the racism towards Negros is prominent. According to Westport News, a firmRead MoreTo Kill A Mockingbird Judgement Essay1406 Words   |  6 Pagessituation†- Anonymous. This quote can be applied to each character also each person in life. The jury should not laugh at the prisoner because it is only a matter of time before roles can be switched. In Harper Lee s award winning novel, To Kill A Mockingbird, she sets the plot in the small Southern town of Maycomb, Alabama, during the Depression. During this time period, issues like classism, racism, genderism, and general stereotyping were quite prudent. Harper reveals that it is unjust for oneRead MoreTo Kill A Mockingbird Literary Analysis Essay1026 Words   |  5 Pages Harper Lee’s To Kill a Mockingbird demonstrates organic unity through the use of literary tools to create, maintain, and amplify the central theme. Lee constructs and develops the theme of social inequality by employing dialogue, irony, and an extended metaphor. Through dialogue, the townspeople show contempt for blacks, viewing them and anyone who treats them as equals as inferior. This is evident in the analysis of the conversations of Bob Ewell, Mrs. Dubose, and Francis Hancock where they referRead MoreComparison of Two Texts, â€Å"One Flew over the Cuckoo’s Nest† and â€Å"to Kill a Mocking Bird†1914 Words   |  8 Pa gesComparison of two texts, â€Å"One flew over the Cuckoo’s Nest† and â€Å"To Kill a Mocking Bird† | How do the authors of To Kill a Mockingbird and One Flew over the Cuckoo’s Nest use literary techniques to explore the concepts of isolation? Isolation and courage in the form of racism and discrimination is an analogous concept explored in Harper Lee’s novel To Kill a Mockingbird and Ken Kesey’s novel One flew over the cuckoo’s nest. The authors exemplify the conflicts of isolation displayed by theRead MoreAnalysis of To Kill a Mockingbird by Harper Lee Essay1360 Words   |  6 PagesAnalysis of To Kill a Mockingbird by Harper Lee In 1960, Harper Lee published her critically acclaimed book To Kill a Mockingbird. Only a year after being published the American classic novel was awarded the Pulitzer Prize in fiction as well as the Brotherhood Award of the National Conference of Christians and Jews. Gregory Peck stared as Atticus in the successfully adapted 1962 motion picture of To Kill a Mockingbird that won an Academy Award. This book is based on many childhood experiencesRead MoreArchetypal Criticism In To Kill A Mockingbird Essay1334 Words   |  6 PagesLiterary criticism is informed, written analysis, evaluation of a work of literature based on literary theory. One literary theory is archetypal criticism which discusses reoccurring symbols, themes, and situations that operate on universal scales that are easily recognized and understandable by the reader. In the novel To Kill a Mockingbird Harper Lee exhibits archetypal criticism. From the archetypes readers are able to understand the characters better and how their actions move the story alongRead MoreKill A Mockingbird, By Harper Lee1599 Words   |  7 PagesPulitzer Prize winner ‘To Kill a Mockingbird’ (1960) is a semi-autobiographical novel written by Harper Lee. Narrated through the eyes of young Jean Louise Finch (Scout), it is set in the fictional Maycomb County, Southern Alabama in the 1930s. The novel traces Scout and her brother Jemâ⠂¬â„¢s journey from a perspective of childhood innocence to adult maturity as they grow up under the moral code of their widowed father Atticus. Atticus accepts the demoralising task of defending an African-American who

Symbols and Motifs in Literature

When you read a book, you might notice recurring themes within the text, which usually influence the storyline and provide clues into the plot or conflict occurring. In order to build and explain the theme, the author will use symbols and motifs. Many readers fully understand what a symbol is, but not everyone is as familiar with motifs. While they are similar and both serve to help us understand the material at hand, these two types of language arent the same. Both are crucial parts of creating a strong storyline that will draw in the reader and hold his attention. What is a symbol? A symbol is an object that represents something else, and in fact, are a part of your daily life, not just a piece of literature. You may not realize it, but you  encounter millions of symbols in your everyday life, such as: Traffic lights: Red light means stop, green means go, and yellow means cautionThe arrow means this wayA cross represents religion, or more specifically, ChristianityLight bulb means new ideaNumerals 1 and 0, put together, mean tenA heart means loveLogos represent brands, like the Nike swoosh or Macs AppleEven our names are symbols that represent us as individual humans Symbols can hold unexpected meaning, but upon further investigation, can make a lot of sense. For example, if you read a scene that involves a skunk lurking in the background, you might wonder what that animal could signify. But, if  theres something that foul in the works of your story, like a breakup or a bit of bad luck, the skunk begins to bring up imagery of something that is less than pleasant to experience. Thus, the symbolism.   To better understand symbolism, you might  ask yourself to consider what a variety of everyday objects might stand for if they were used in a piece of literation. For example, think about emotions or thoughts that come to mind when you see the following: Flowers (represent nature, birth, growth, femininity, beauty)Lightening bolt  (represents speed, strength, power, electricity)  Spider web (represents entanglement, entrapment, mystery) What is a motif? While a symbol might occur once in literature to signify an idea or an emotion, a motif can be an element or idea that repeats throughout that piece of literature. It is closely related to a theme but is more of a supporting role to the theme than a theme itself. It is within the pattern of repetition that the power and impact of a motif are found. A motif could, in fact, be expressed by a collection of related symbols. How do symbols and motifs work together? Since multiple symbols can be used to explain a motif, lets break down a few examples. Lets say we have a story about a family struggling to stay together, parents considering divorce. We might encounter a motif of fragmentation that could come from several symbols that appear in a book: Shattered glassA runaway (pet, teen, car)An explosionA scattered puzzle Sometimes a motif can also be a study on contrast, like the theme of good versus evil, or light and dark. A series of symbols that could represent this motif might be: Moon shadows (shades of darkness)A candle (a light in the darkness)Storm clouds (temporary darkness)A ray of sunshine (emerging from darkness)A tunnel (through the darkness) The symbols and motifs you discover in your reading will lead to the understanding of an overall theme of your book. To find the theme of a book, you should look for an overall message or lesson. If you do encounter the motif of light and dark in a book, you should think about a message that the author is trying to send about life. The light and dark of a story might tell us: Love survives deathLife renews itselfKnowledge conquers fear Tip: if you see a series of symbols or a collection of motifs, but you cant come up with a theme, try inserting a verb to describe the object.  If you see a lot of references to fire, for example, you can ask yourself what action we might associate with fire. Fire burnsFire destroysFire warms Consider which of these behaviors make sense in the context of the novel or story you are reading.

Corporate Social Responsibility ( Csr ), And Conscious...

Everything that we as individuals do adds value to society. Through our actions, we strive to create a way for people to cooperate and get things done efficiently. This value driven movement exists through an acknowledgement of purpose beyond just making a profit. Servant leadership, corporate social responsibility (CSR), and conscious capitalism are practices designed to achieve this goal upon their implementation by organizations. All three of these theories have the same objective to serve the greatest number of stakeholders. However, the tactics employed by each are seemingly different. Similar to a car engine, conscious capitalism and servant leadership each represent components of the machine necessary to successfully drive the car, while CSR is an optional extra; especially for businesses with a well-established economic engine. A vehicle cannot run without its engine. Likewise, in today’s advancing world, conscious capitalism is a necessary component in the effective operation of an organization. The values that fuel this engine include conscious leadership, stakeholder orientation, conscious culture, and a higher practice. Whole Foods is the greatest example of conscious capitalism. As part of their philosophy, there is a balance between what’s good for shareholders, employees, customers, vendors, the community, and the environment. Whole Foods ultimately believes that all stakeholders are important, which makes it necessary for everyone to cooperatively workShow MoreRelatedCase Analysis: John Mackey, Whole Foods Market Essay examples1702 Words   |  7 Pagesits employees engaged and not just â€Å"feeling† heroic or happy. 2. How does Whole Foods build human and social capital? Human capital is important for any business, because humans need to be productive and knowledgeable to be successful. John Mackey says he hires happy employees, encourages employees to flourish, and ensures that they are well trained. He is not only creating a conscious culture, but he envisions a culture of engagement through leadership. Some ways that they can increaseRead MoreThe On Conscious Capitalism By John Mackey And Raj Sisodia1918 Words   |  8 Pageshas never seen before. According to Doug Levy’s presentation on Conscious Capitalism, Capitalism has been the major factor in ending poverty in our world. If current trends continue at the rate they do today, extreme poverty will be nearly eliminated over the next few decades. In the texts Conscious Capitalism by John Mackey and Raj Sisodia, The Art of Servant Leadership by Tony Baron, and the practice of Corporate Social Responsibility presented by Ed Ahnert, there is a co-existing relationship leadingRead More The On Conscious Capitalism By John Mackey And Raj Sisodia1918 Words   |  8 Pageshas never seen before. According to Doug Levy’s presentation on Conscious Capitalism, Capitalism has been the major factor in ending poverty in our world. If current trends continue at the rate they do today, extreme poverty will be nearly eliminated over the next few decades. In the texts Conscious Capitalism by John Mackey and Raj Sisodia, The Art of Servant Leadership by Tony Baron, and the practice of Corporate Social Responsibility presented by Ed Ahnert, there is a co-existing relationship leadingRead MoreMarketing Plan For Whole Foods Market1401 Words   |  6 Pagesby a few key players. They have managed to break away from the traditional supermarket model and become the leading retailer in natural products as a result of the global trend towards clean eating and the health conscious consumer. They have successfully pulled away from the corporate aesthetics of many American supermark ets and taken it back to market stall style presentation within the shops and an emphasis on freshness. This is backed up by figures which show that in 2013 organic and naturalRead MoreCorporate Social Responsibility ( Csr )1216 Words   |  5 Pagesdefinition of corporate social responsibility (CSR) has been much deliberated and remains controversial. The research of Marrewijk (2013, p.95) elaborated on the significance of this ongoing debate among academics, consultants and corporate executives which results in creating, supporting and criticising of different concepts. This essay illuminates CSR principles, consider different definitions and concepts and relates it to my definition. Furthermore, it supports companies’ interest in CSR only forRead MoreThe Representation Of The Corporate Social Decisions And Activities1504 Words   |  7 Pages4.2 Legitimacy Theory The corporates were suggested by Hogner (1982) to legitimize their corporate social decisions and activities. In 1983, Lindblom stated a framework about legitimacy theory to explain why companies should disclosure the social information and environment information. Many social studies relied on this framework to claim the theoretical structure. The legitimacy theory was born to strengthen objective of the corporate management to react to the expectations of the community membersRead MoreThe Social Responsibility Of Business1042 Words   |  5 PagesCorporate Social Responsibility is defined as a business preparation that involves participating in creativities that help society. Friedman: The Social Responsibility of Business is to increase its profits. Milton Friedman argues that the only social responsibility a business has is to itself – mainly to its profits, and therefore, its stakeholders. The business management in charge of a company works for the organization and eve ntually for the stakeholders. This person is responsible for carryingRead MoreTexas Instruments in South Korea1347 Words   |  6 Pagesinstruments, 2014). It is this culture of risk taking that has TI attempting to partner with South Korea as a first mover in the digitization of learning for children K – 12. This digitization initiative is targeted for completion by 2015 (Peng, 2014). Social status surrounding a person’s education is critical within the South Korean culture (Asia society, 2014). This emphasis on education highlights South Korea’s transformation over the last half century from a government of dictatorship into a democraticRead MoreIntegration Assignment : Company Overview And Strategy Essay960 Words   |  4 Pagesmarketing services that allow them to reach new customers (Fortune). The company provides this service to their customers through a technique called inbound marketing. Through inbound marketing, companies attract prospective customers through the use of social media, blogs, and search engine optimization (Harvard Business Review). One of HubSpot’s specific tools is the Customer Relationship Management software, abbreviated as CRM. HubSpot CRM is a free, easy to use service that helps businesses automaticallyRead MoreA Responsibility Of Business Society : A Review And Issues Essay2042 Words   |  9 Pages Research Paper on A Responsibility of Business to society: A Review and issues Abstract: Corporate Social Responsibility (CSR), a concept that has been around for well over 50 years, has become prominent again recently. Peter Utting (2005) notes that an increasing number of transnational corporations (TNCs) and large domestic companies, supported by business and industry associations, are adopting a variety of so-called voluntary CSR initiatives that incorporate, for example, ‘codes of conduct;

Creativity or Conformity Building Cultures of Creativity in Higher Education free essay sample

Permission is granted to reproduce copies of these works for purposes relevant to the above conference, provided that the author(s), source and copyright notice are included on each copy. For other uses, including extended quotation, please contact the author(s). Abstract Whatever else it may be, creativity is intriguing; this view appears to be shared by the literature on the subject and by popular culture. While there is little agreement about the exact nature, processes and products of creativity, there seems to be a fascination both with its complexity and the sheer impossibility of providing clear explanations for it. This paper does not attempt to generate yet another explanation, but instead offers a framework for exploring creativity in the context of teaching and teacher education. The nature of creativity in teaching is usually evidenced by its products: innovative curriculum design or original students’ work. The focus of this paper, however, is on developing opportunities for teachers to understand, explore and express their identities as creative practitioners. These opportunities are offered in the form of â€Å"creative reflection†, a framework of creative methodologies for engaging teachers individually and collectively in identifying and expanding their creativity practices. The notion of creative reflection challenges the action-reflection dichotomy of reflective practice and extends reflection beyond cognitive, retrospective models to encompass the exploration of possibility through play, image-making, writing, action methods and storytelling. The paper offers examples of and reflections on these methods from the author’s use of creative methodologies in a teacher education programme at Queen’s University Belfast. Creative Reflection, Creative Practice: Expressing the Inexpressible The concept and practices of creative reflection have been developed in a teacher education programme at Queen’s University Belfast to enhance the model of reflective practice on which the programme is based. Creative reflection is a framework of creative methodologies whereby teachers explore their practice and the liminal spaces between action and reflection. This work is a response to the need in teacher education for â€Å"the development of more complex models of reflection, related to purpose, which take greater cognisance of existing knowledge from other disciplines, particularly those aspects of psychology concerned with cognitive processes including problem-finding, insight, wisdom, creativity† Leitch and Day (2000: 186-187). Creativity itself is an elusive concept; the literature on the subject incorporates a range of perspectives and dichotomies, raising a number of questions. Those pertinent to this paper include: is creativity a cognitive process, or is it socially constructed? is creativity to do with outcomes, or with processes and qualities such as fluency, imagination and originality? what are the conditions which support the development of creativity? what is the nature of creativity in education, and does it have a place in teacher education? One of the assumptions on which this paper is based is that teachers are creative; by extension, teacher education should therefore provide them with opportunities to identify themselves as creative and to enhance their creativity. Craft (2001: 48) suggests that teachers are highly creative: Certainly some of the characteristics of high creators (childlike qualities, feeling under siege, being on the edge, high energy and productivity) which Gardner identifies in Creating Minds (1993), also emerged as a characteristic of ‘ordinary’ educators in one of my research projects (Craft, 1996a; Craft and Lyons, 1996). Craft’s allusion to productivity is complemented by Eisner’s exploration of the processes, the â€Å"artistry† and the â€Å"craft† involved in teaching (2002). Both facets of creativity, product and process, are incorporated into the framework for creative reflection. Details follow as to how participants engage in process activities as well as in deliberation on the outcomes of these processes. The process of creativity, mysterious as it is, has long been a source of fascination and speculation. Helmholtz’s classical model, developed in 1826, includes the stages of saturation, exploration and incubation; Poincare added to these the aspect of verification (Balzac, 2006). The four-phase model developed for this study incorporates and elaborates on these stages: Model for Creative Reflection Phase 1: Preparation This aspect of creative reflection recognises that the creative process involves uncertainty and possibility and that participants need preparation to access that state of receptivity, or Keatsian Negative Capability, which Keats defines as â€Å"when a man is capable of being in uncertainties, mysteries, doubts, without any irritable reaching after fact and reason† (Buxton Foreman, 1895). In this phase of creative reflection, threshold activities are offered to enhance possibility and to free the imagination. One of the most successful of these threshold activities has been the invitation to participants to select images and quotations on a relevant theme: teaching, learning or creativity itself. This activity is based on the notion of â€Å"stepping stones† into a liminal world of exploration, as in Progoff’s system for entering the â€Å"twilight world† of process meditation (Progoff, 1980). While participants are in the process of choosing images and quotations which engage them, music is played in the background to enhance relaxation and stimulate intuitive rather than rational decision-making. The activity is conducted without discussion to encourage focus and a connection with the unconscious. Another threshold activity is that of visualisation: for example, individuals are asked to imagine their learning about their practice as a journey and to articulate this in the form of images or writing. The sharing of the results is part of the process of synthesis described in the final phase of this model. Threshold activities are directed at the group as a whole as well as at individuals: for example, participants are asked to imagine an ideal space for teaching and learning and to suggest in turn something which they might like to include in this space. Offerings range from comfortable chairs to the location of this space at the seaside and the presence of flowers and music centres. This activity generates ideas about inclusiveness and introduces into the discussion metaphors and symbols which enhance the learning process. The idea of bringing an ideal situation or world into the realms of possibility through group visualisation is based on the process of reflective meditation in psychosynthesis (Ferrucci, 1982; Assagioli, 1999). Phase 2: Play This phase is based on the assumptions that a good deal of learning happens through play, that play is an essential aspect of cultural development (Huizinga, 1970), and that a group can create meaning, possibility and new insights through the processes of play. Play is also important because it has the potential to free participants from external concerns so that they may enter the state of â€Å"flow†. According to Csikszentmihalyi (1991, 1997) this is an optimum state in which the person is fully focused and immersed in what he or she is doing, usually with a successful outcome. The activities in this phase are conducted quickly; their purpose is to generate energy, enjoyment of the group process and a range of new ideas. The processes involved provide opportunities for divergent thinking; they include mind mapping, creative thinking and brainstorming. The brainstorming methods in this model of the creative reflection are informed by Kelley and Littmann’s (2002) methods for enhancing fluency of ideas and innovation within the context of team-building. Phase 3: Exploration This aspect of creative reflection is active, with the purpose of creating a product. The processes involved may include creative writing, storytelling, or the use of art materials, or action methods based on psychodrama to concretize the experience (Moreno, 1994). The exploration phase may be individual or collective: it may take place in pairs or small groups. In one particular activity, an individual selects one of his or her identities as a teacher from a list; this list includes the more obvious identities such as mentor, helper and instructor, as well as more metaphorical ones as foot soldier, sower or bridge. The individual then elaborates this identity through writing and art, imagining in detail, for example, what this identity might look like, its voice, its tools and how it engages in relationship. The image below depicts the process of exploration on both individual and group levels. Participants, given the task of expressing their understandings of themselves as reflective practitioners, arranged together the quotations, images and artefacts which they had chosen as individuals to express this notion. The circle of people made from tissue paper was created as a collective piece for the final image; this suggests that the group product extended beyond that of a loose arrangement of individual ideas to a creative collaboration of knowledge and understanding. [pic] Phase 4 Synthesis In the final phase of creative reflection, which is akin to the verification tage of the Helmholtz/Poincare model, participants present and reflect on their ideas, stories and collective images. In this phase, which is adapted from McNiff’s process of â€Å"dialoguing with the image†, participants engage with and reflect on the artefact engendered by the creative process (McNiff, 1992). Through this process, the experience and learning are synthesised into new understandin gs, or the identification of new questions which might be raised about professional practice. The image below represents the world of reflective practice as created by a group of practitioners through the use of props. pic] Discussion about this image revealed that each of the scarves, which are circumscribing and containing the world of reflective practice, represents a strength owned by one of the practitioners, while the Russian dolls and the teddy bear on the edge of the circle symbolise those learners who exclude themselves from learning. The act of dialoguing with the image engendered ideas amongst the participants for engaging those who are currently on the outside and who have not yet found a satisfactory means of expression. In many ways, the process of writing this paper has been a struggle to express that which is inexpressible; it is challenging to articulate the complexity of the spaces between reflection and practice, as well as the complexity of creativity itself. It is hoped that further research will indicate whether the processes of creative reflection can take sufficient cognisance of these complexities to support teachers in recognising and expressing their creativity. References Assagioli, R. (1999) The Act of Will: A Guide to Self-Actualization and Self-Realization, Knaphill, David Platts Publishing Company Balzac, F. (2006) ‘Exploring the Brain’s Role in Creativity’,Neuropsychiatry Reviews, Vol. 7, no. 5, May 2006. http://www. neuropsychiatryreviews. com/may06/einstein. html Accessed 14/11/2006 Buxton Foreman, H. (1895, Complete revised edition) The Letters of John Keats, London : Reeves Turner Craft, A. (2001)’ â€Å"Little c Creativity†Ã¢â‚¬â„¢, Craft, A. Jeffrey, B, and Leibling, M. (eds. ), Creativity in Education, London and New York, Continuum, pp 45-61 Craft, A. (1996a) ‘Nourishing educator creativity: a holistic approach to CPD’, British Journal of In-Service Education, 22 (3), 309-322. Craft, A. and Lyons, T. (1996) Nourishing the Educator, Milton Keynes: The Open University Seminar Network Occasional Paper Series Csikszentmihalyi, M. (1997) Creativity. Flow and the Psychology of Discovery and Invention. New York, HarperPerennial. Csikszentmihalyi, M. (1991) Flow: the psychology of optimal experience. New York : HarperPerennial Eisner (2002) ’From episteme to phronesis to artistry in the study and improvement of teaching’, Teaching and Teacher Education, Volume 18,  Number 4, May 2002, pp. 375-385 Ferrucci, P. 1982) What we may be: techniques for psychological and spiritual growth. New York: Jeremy P. Tarcher/Putnam Gardner, H. (1997) Extraordinary minds: portraits of exceptional individuals and an examination of our extraordinariness New York : BasicBooks Huizinga, J. (1970) Homo Ludens: a study of the play element in culture, London : Maurice Temple Smith Kelley, T and Littman, J. (2002) The Ten Faces of Innovation: Ideos Strategies for Beating th e Devils Advocate Driving Creativity Throughout Your Organization London: Profile Leitch, R. and Day, C. (2000) ‘Action research and reflective practice: towards a holistic view’, Educational Action Research, Vol 8, 1 pp179-193. McNiff, S. (1992) Art as medicine: creating a therapy of the imagination Boston, MA. : London: Shambhala Moreno, J. L. (1994, Fourth Edition) Psychodrama and Group Psychotherapy, Mental Health Resources. Progoff, I (1980) The Practice of Process Meditation: The Intensive Journal Way to Spiritual Experience, New York: Dialogue House Library.

Was Us Justified in Using the Atomic Bomb in Japan free essay sample

Over the history of the United States, people have been debating over the issue of US using the atomic bomb on Japan. Some may feel that United States was justified and others might feel that US was not justified. The usage of atomic bomb in Japan might seem wrong today, but it was the best option during the war. The United States was justified in using the atomic bombs against Japan in World War II. Some may feel that the United States was justified in using atomic bombs against Japan. The US was obligated to use the atomic bomb, because, after the Potsdam Conference in July, US asked the Japanese to surrender in early August. Japanese said â€Å"no† and that they would never surrender. This left Truman with two very difficult decisions; one: keep fighting or two: use the atomic bomb to end the war. Truman chose the usage of atomic bomb on Japan to end the war quickly, by doing this, he saved tenth of thousands of American soldiers lives. We will write a custom essay sample on Was Us Justified in Using the Atomic Bomb in Japan? or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page According the Truman’s Decision to Drop the Bomb; four cities were recommended as targets: Hiroshima, Kokura, Niigata, and Nagasaki. The bombs were dropped on Hiroshima and Nagasaki, because of fewer populations. The atomic barely got the Japanese to surrender. Us dropped two, then only with the intervention of the Emperor and even then, there was an attempted coup to prevent surrender. If US have hadn’t used the bomb, the war could have lasted for decades. Others may feel that the United States was not justified in using atomic bombs against Japan. The drop of the bombs on Hiroshima and Nagasaki killed hundreds of thousands of people. It was unnecessary for United States to use 2 bombs on Japan, because Japan was already largely defeated. According The Ordeal of Hiroshima; it states that: people were having a normal, joyful and beautiful day then suddenly all gone in flash of light. The doctor describes how the city was in peace in one minute and how it was incinerating in the other. People were in agony as well as him. US killed innocents of people, they have committed a war crime and they have to be trialed for this. Not only people were killed my explosion, they were also killed by radiations. The US had no idea what the bomb could do before they dropped it. The bombs have been affecting the new born babies up to today. It was not right and it was not necessary. The United States was justified in using atomic weapons against Japan. It as either drop the bombs, kill a few thousand people or not drop the bomb, the war lingers on and more people die than the bombs killed. WW2 had to stop and this made it happen. Neither country could afford any more warring on the other, this was a costly expense. True the US killed innocent people, but if they didnt, more would have died at the hands of the Japanese and of the Americans. The bombs not only made sense, they save d lives. The war had to end because the Japanese soldiers were fighting inhumanely; they were fighting with the system of kamikaze. Over the history of the United States, people have been debating over the issue of US using the atomic bomb on Japan. Some may feel that United States was justified and others might feel that US was not justified. Supporters might say that US had dropped atomic bomb to end the war quickly and to save lives. Opponents might say that the usage of bomb killed millions of innocent civilians, it was unnecessary to even use the bomb, because Japan was weakened already. The United States was justified in using atomic bomb, because Japan was given a choice to surrender and they refused.

Study into Drug discovery and Design The WritePass Journal

Study into Drug discovery and Design Introduction Study into Drug discovery and Design Introduction1. Background1.1 Target Identification and Validation1.2 Hit Identification and the Generation of a Lead Series 1.3 Lead Optimisation 1.4 Summary and Aims2. Case Studies2.1 Nuclear Magnetic Resonance in Fragment Based Library Screening and X of A G-Protein Coupled Receptor3. Conclusion3.1 Summary of Main Points and Advantages of Structure-Based Techniques3.2 The Limitations of Structure-Based Techniques3.3 Concluding Thoughts and Future AdvancesRelated Introduction 1. Background Drug discovery and design is fuelled by the need for appropriate and effective treatment for disease. Initially discovery was achieved via empirical screening of vast libraries of molecules, which was incredibly effective. The majority of drugs currently in clinical use were discovered this way. However with increased technology, and a greater need for newer more effective medicines, structural biology has become a prominent tool. The general principles behind drug discovery briefly discussed here include target identification and validation, and hit discovery or design to generate a lead which is then optimised. 1.1 Target Identification and Validation A target is often a protein, however it can also be RNA, DNA or a carbohydrate. People who suffer degenerative, autoimmune and genetic diseases can be screened for genetic differences through genome wide association studies (Grupe et al., 2007)or systematic meta-analysis (Bertram et al., 2007). Infective organisms have genes that are very different to human genes that may be essential in the life or infective cycle of the organism and are thus useful targets that can be identified through bioinformatics analysis or loss of function mutant phenotype studies (Crellin et al., 2011). A structure-based technique includes structural genomics, which is the study of the structures of all proteins in a genome. 1.2 Hit Identification and the Generation of a Lead Series Once a target has been identified and validated, small molecules that bind and in some way alter function must be discovered or designed, again there are a number of ways in which this can be done. Empirical screening has identified a number of drugs, however structure-based techniques are more and more commonly being used. 3D structures from X-ray crystallography data and, to a lesser extent, nuclear magnetic resonance (NMR) have been used to generate the information required for computational methods involving docking and screening. This has been useful, for example in the in-silico screening of G-protein coupled receptor (GPCR) binding molecules (Richardson et al., 2007), however most structure-based drug designs have come from the design of compounds based on the 3D structure obtained from X-ray crystallography or NMR, or via biophysical screening techniques involving surface plasmon resonance (SPR) or NMR. Structure based screening methods often require fragment based libraries. These encompass a greater number of potential molecules, within smaller libraries of compounds, this is possible because there are no large functional groups that would inhibit binding, and so result in attractive starting points for hit discovery (Nordstrà ¶m et al., 2008). To validate or measure the properties of the hits, crystal structures can be evaluated and additional information from secondary SPR screens, thermal information from isothermal titration calorimitry (ITC), and differential scanning fluorimitry (DSF) can be used to complement the data (Retra et al., 2010). 1.3 Lead Optimisation Once validated, the structure is optimised. This can be based on ligand binding structures in NMR and X-ray crystal structures, or increasingly, in-silico modelling based on the pharmocophore hypothesis involving the evaluation of chemical and functional groups that may bind important sites of the target molecule (Voet et al., 2011). The key structural techniques involved in structure-based drug design are X-ray crystallography and NMR, though mass spectrometry can also be used to observe proteins in multi-protein complex interactions. X-ray crystallography generates 3D structures of the protein of interest from crystals generated by altering conditions such as buffers, pH, temperature and the format; nanodrop, hanging drop as well as others (Giegà © Sauter, 2010). These crystals are homogenously packed and stored in cryo-protecting buffers so that they can be stored in liquid nitrogen which protects them from the X-rays used to generate the 3D structural information (Philippopoulos et al., 1999). Once obtained, if the ligand of interest is soluble and has relatively high affinity for the target protein, co-crystallisation studies can be used to look at interactions of the different ligands of interest with the target protein. This is not always possible; however there have been improvements since the advent of fragment based libraries. NMR based structures are more time consuming to construct, requiring the analysis of NMR peaks of different spectra to associate them with specific nuclei to generate restriction information to produce a structure. Though more time consuming, it is incredibly useful if other forms of structural information are not available (Zou, 2007). In structure-based drug design NMR has been more useful in ligand protein interaction studies (Pellecchia, 2005), but has also been used in screening libraries for hit molecules (C. Murray et al., 2010). Mass spectrometry can be used in each stage of drug discovery (Deng Sanyal, 2006), especially as technology advances, however it is much more limited (justification?) than those methods or techniques already mentioned and so will not be discussed in any great detail. To complement these techniques there are a vast array of technologies available, a few of which are   mentioned below. SPR measures interactions between the target protein and potential hits in biosensors, and can also be used in hit validation and optimisation in secondary screens (Retra et al., 2010). Since fragment based screening, SPR has become much more popular and will be discussed in greater detail later. Other complimentary techniques involves ITC which measures entropy and enthalpy to determine their contributions in ligand interaction, and therefore gives a clue as to what sorts of alterations would be required to optimise binding. DSF is also widely used, more often to measure where the hit compound is binding on the target molecule (Domigan et al., 2009). 1.4 Summary and Aims To summarise, the stages of drug design include target identification and validation; hit identification and generation of the lead molecule; and then the optimisation of the lead into a drug for testing and then clinical trials. Target identification may utilise such structural techniques as structural genomics. Hit identification makes better use of structural information from X-ray crystallography or NMR and the design of drugs and computational in-silico drug design, or screening methods including high throughput screening (HTS), SPR library screens, and in silico computational screening methods. Optimisation generally uses structural information taken from X-ray crystallography as well as computational methods and in some cases NMR aided by SPR, DSF and ITC to increase binding affinity and then the pharmacokinetic properties. To assess their usefulness in structure-based drug discovery and design, case studies will be analysed to look at how these techniques have been used to further the production of clinically used drugs, or at least increase our understanding so that we may be able to use it in future drug design attempts. 2. Case Studies 2.1 Nuclear Magnetic Resonance in Fragment Based Library Screening and X-ray Crystallography in the Design and Optimisation of Hsp90 Inhibitors The heat shock protein 90 (Hsp90) is a human chaperone which is involved in stress responses, but is also required in the essential process of client protein maturation. Many of its client proteins are involved in cell signalling, proliferation and growth (Biamonte et al., 2010), which have been associated with a number of different cancers. The overexpression or inappropriate activation of Hsp90 is also therefore associated with cancer, therefore a number of drugs have been produced which aim to inhibit the essential ATPase activity of Hsp90. Hsp90’s combinatorial in so many different client proteins makes it a good target for drug development, therefore many drugs are already available that target Hsp90. However there are a number of problems concerning bioavailability, toxicity and increased resistance and so newer more effective drugs are required (Van Montfort Workman, 2009). As can be seen in figure 1 Hsp90 is active as a dimer, and in the N terminal of each subunit is a functionally essential ATPase site (Prodromou et al., 1997), the middle domain regulates the interaction of Hsp90 with its client proteins (Meyer et al., 2003) and the C terminal region is responsible for dimerization (Minami et al., 1994). Initially drugs for Hsp90 were discovered using the binding and cell based assays, however more recently there have been drugs that have entered clinical trials that were generated using structure-based techniques. These have targeted the ATP binding site essential for function, and so required a good understanding of this site. As can be seen in figure 2 there are critical hydrogen bongs between the adenine of the ATP bound, and the side chain of the amino acid residues Thr184 and Asp93 . These would therefore be ideal targets in the design of an inhibitor molecule (Obermann, 1998). There are examples where inhibitors have been identified using NMR and X-ray crystallography screening methods of fragment libraries, and as has been described, fragment based libraries generate useful starting hits (Hartshorn et al., 2005). In an NMR fragment based library scan, the displacement of low concentrations of ADP (the product compound of the ATPase domain)was measured using NMRwaterLOGSY (Water-Ligand Observed Via Gradient SpectroscopY) (Dalvit et al., 2001), which indicated when a fragment had bound which could be chosen for further study (Murray et al., 2010). Murray et al. discovered a number of binding fragments, 2 of which became lead compounds. The first was compound 1 (fig3) which made extensive hydrogen bonding interactions with key residue Asp93 (as seen in figure 2) and a number of water molecules found deep within the binding pocket as can be seen in figure 4a. However, as can be seen in figure 4b the compound 1 doesn’t efficiently fill the lipophilic pocket defined by the residues Met98, Leu107, Val150, Phe138 and Val186, additionally it was found that compound 1 wasn’t particularly stable, as it was twisted about the bond between the pyridine and pyrimidine. Virtual screening for analogues was used initially to produce more stable forms of compound 1, and though this yielded higher affinity binding molecules, their torsion profiles indicated steric clashes between the methoxy group at position R2 (fig5a) would result in unfavourable binding. Instead using SAR (specific absorption rate) analysis, it was predicted that exchanging the methoxy for chloro improved it significantly, resulting in compound 9, the basis of further optimisation outline as a chemical structure in figure 5b, with the positions for optimisation labelled as R4 and R5. This was done using computer based modelling techniques, and illustrates how useful it can be when enough information regarding the target protein and the current ligands is available. The methoxy and chloro groups added to positions 4 and 5 of the upper phenyl ring increased binding affinity to the lipophilic binding pocket to 12nM. Once the affinity was increased, cellular activity had to be improved and this was achieved by adding a morpholine group to position 5 outlined in figure 5b, a decision based on the crystal structure, and this resulted in compound 14 which is currently going through clinical trials for the treatment of different cancers. As can be seen in figure 6, compound 14 in blue binds in much the same way as compound 1 in orange, but makes more extensive interactions with the lipophilic pocket via an extended phenyl ring. The second line of lead compounds Murray et al. followed initiated from compound 3 (fig7), which using their initial NMRwaterLOGSY screening method appeared to bind rather inefficiently. However, upon observation of the X-ray crystal structure of Hsp90 bound to compound 3 (fig8) it was decided that it provided a quick and attractive optimization route. It’s binding with water molecules and one of the key residues Thr184, though on its own provided a relatively weak interaction, if optimised could also make direct interactions with the alternative key residue Asp93, and also with additional endogenous water molecules. Using trial and error, the writers found that a tetra-butyl group filled the lipophilic pocket appropriately with fewer steric clashes, and this resulted in compound 18, the lead compound that was further optimized to make more effective interactions within the lipophilic pocket. Using modelling studies, interactions with the side chain of residue Lys58 was approved. Compound 24, an isoindoline filled the pocket with a phenyl ring which interacts with residues Ala55, Lys58 and Ile96 completely displacing Lys58 side chain as can be seen in figure 9a. In other inhibitors a position 2 OH (hydroxyl group) resulted in the greater affinities, however compound 18 had a position 4 OH, and a replacement with an OH at position 2 resulted in a lower affinity compound. Addition of an OH at position 2 to compound 24 as well as the OH at position 4 resulted in compound 31 which enabled interactions directly with Asp93, retaining interactions with Thr184 as well as increasing hydrogen bonding with water molecules as can be seen in figure 9b. It also , illustrates compound 31 in blue binding in much the same way as compound 3, but it fills the lipophilic pocket more efficiently, and makes more extensive interactions. This greatly increased binding affinity and compound 31 is now going through clinical trials. This helps illustrate the importance of structure-based approaches such as NMR and X-ray crystallography in the identification and optimization of lead compounds, as well as the input computer based methods can have. X-ray structures were particularly helpful in the case of compound 3, as without this structure compound 3 would have been dismissed as an inefficient binding compound. Additionally, all kinetic data which helped support the optimization and validation steps, was obtained using ITC. Further work on improvements to the pharmacokinetic properties as well as drug-tissue distribution should be concentrated on. 2.2 Crystal Structures from X-ray Crystallography and Nuclear Magnetic Resonance in In-Silico Drug Design, and 3D Drug Development Human Immunodeficiency Virus HIV (the human immunodeficiency Virus) is the causative agent of the acquired immune deficiency syndrome (AIDS) and statistics show that by 2005, approximately 38 million people worldwide were living with HIV (Beyrer, 2007). HAART (highly active anti-retroviral therapy) established in the 1990’s makes living with HIV bearable by keeping viraemia low, and CD4+ (cluster of differentiation 4) cells at a high enough level to protect from opportunistic pathogens. However, with increasing resistance and the negative side effects of current drugs, constant improvement and newer drugs are required. The protease inhibitors were revolutionary in HIV treatment, starting with the rationally designed Saquinavirapproved for use in 1995 (Roberts et al., 1990). HIV protease is a good target, essential in the life cycle of the virus, and though Saquinavir was very successful, resistance quickly arose, and so a greater understanding of the protease structure and biochemistry was required. This was necessary not only to try and target residues that would be less likely to result in resistance, but also to improve the pharmacokinetic properties, producing non-peptidic as opposed to peptidic drugs to reduce toxicity and improve half-life (Arung Ghosh et al., 2008). There have been multiple inhibitors designed with the use of X-ray crystallography, to enter clinical trials and be approved by the FDA (food and drug administration) for use in HAART. It was determined that by targeting the protease backbone residues, it would be possible to generate drugs that would be less likely to result in resistance because mutations are rare, and those that occur do not often distort the overall conformation. Such a site is therefore more conserved and a better drug target (Ghosh et al., 2011). Saquinavir, though a peptidic drug with poor pharmacokinetic properties did bind the backbone resides (though relatively weakly) it also bound outside of the binding envelope, the region which locates the gag-pol polyprotein for cleavage. Mutations are far more common and tolerated outside of the envelope region. Mutations would therefore not reduce virion viability but would prevent inhibitor binding (King et al., 2004). The development of Aprenavir, with a single-ringed tetrahydrofuran (THF) group was designed using Saquinavir as a scaffold, to generate a related, but non-peptidic cyclic compound that would bind and inhibit the active site of the protease, much in the same way as Saquinavir but with increased half-life, better pharmacokinetic properties, increased backbone binding and a more specific binding to the active site envelope. The chemical structure of Aprenavir as seen in figure 9, binds the S1S2 S1’S2’ binding envelope of the protease, closely interacting with the backbone residues Asp29 and Asp30, as well as many other residues (Kim, 1995). The interactions with Asp29/30 were relatively weak, and the THF group, believed to be involved in increasing favourable enthalpy interactions, if increased in size was thought to be able to improve backbone and hydrophobic interactions with the residues that make up the lipophilic flap. Using Aprenavir as a scaffold, Darunavir was developed, a bis-THF compound with a double ring, as can be seen in figure 10. This single ringed to double ringed evolution resulted in more extensive interactions with the key backbone residues (Tie et al., 2004) as can be seen in figure 10, as there are far more hydrogen bonds present between the bis-THF complex in pink with the backbone residues than there are between the single ringed THF complex in green. To measure the ability of Darunavir to withstand mutations in HIV protease, Tie et al. co-crystallised Darunavir with a wild type protease and a mutant version. As can be seen in figure 11, the wild type hydrogen bonds at 4.1 Ã… indicated by the purple dashed lines   is retained in the mutant distance of 3.8 Ã… in blue. This suggests that Darunavir is robust, and will continue to be active against resistant strains of HIV. The inherently high mutation rate of the HIV genome due to the accident prone polymerase means that there will be strains that will become resistant to Darunavir in the future, and it is always necessary to stay one step ahead. Darunavir has thus been used in modelling studies to design optimised structures which are incredibly potent, more so than Darunavir retaining the favourable pharmacokinetic and cellular properties (Ghosh et al., 2011). Figure 12 details the position of compound 1b in green– a Darunavir like compound in the hydrophobic pocket of the HIV-1 protease, and as can be seen, it makes a number of Van der Waals interactions with residues Ile47, Val32, Il84, Leu76 and Ile50’ which make up the hydrophobic flap as well as hydrogen bonds with Asp30 (3.5Ã… long) and Asp29 (2.9Ã… long). To improve the interaction distance with Asp30’s NH group, Ghosh et al. modelled an increase in phenyl ring size of the P2 ligand   in an attempt to also increase flexibility of the structure. This was achieved with the addition of an amide group which also increased the hydrophobic interactions with the lipophilic pocket residues. The pink structure of compound 35a as seen in figure 12 binds in much the same way as compound 1b, but makes more extensive interactions with the key residues and fills out the lipophilic pocket more effectively. This compound was then generated and its Ki and IC50 values cal culated to measure it against 1b, it was a far more efficient inhibitor, and thus a potential clinical candidate. There are many examples of proteins that cannot be crystallised, and to obtain structural information so rather than using X-ray crystallography, NMR can be used. As an example, the HIV protease structure was constructed using NMR (fig 13).An X-ray crystal structures is a static representation of a dynamic system in a relatively unnatural environment, whereas NMR is in solution and is believed to be more biologically relevant, and can in some circumstances be used to observe dynamic protein systems (Zou, 2007). NMR is far more time consuming however, and the inherent flexibility of proteins results in areas of low resolution in structures, more so than with X-ray crystallography. NMR has been used more successfully in hit identification, as has been discussed in the example of Hsp90 inhibitors. 2.3 The use of Surface Plasmon Resonance, Isothermal Titration Calorimetry and In-Silico Drug Design to Complement Structural Techniques Such as X-Ray Crystallography and Nuclear Magnetic Resonance As technology improves newer methods have evolved that complement the existing, this includes such techniques as SPR which detects the interactions between the target protein and ligand, used in primary fragment based library screens to identify hits, or secondary screens to identify or validate hits (Retra et al., 2010). As previously discussed, fragment based screening methods can result in attractive starting points for lead optimisation (Erlanson, 2006). SPR can be used in a number of ways, in chemical micro arrays, SPR imaging, secondary screens of hits found through high throughput screens and also in primary biosensor screens. In primary screens, a biosensor is set up with the target molecules immobilised on chips and this has been successfully used in the identification of hits without the requirement of other forms of structural information (Nordstrà ¶m et al., 2008). The hit molecules can then be integrated into lead series and optimised using other structural techniques such X-ray crystallography and NMR to obtain clinical candidates (Huber, 2005). The matrix metalloproteinases (MMPs) are a group of proteins found in many different species; in humans there are approximately 12 that are involved in tissue remodelling, and degrading extra cellular matrix molecules such as elastin, collagen and laminin (Demedts et al., 2006). MMP-12, involved in various human diseases such as emphysema and chronic obstructive pulmonary disease (COPD) is the target of a number of therapeutic drugs, all of which have harmful side effects and so new drugs are required (Nordstrà ¶m et al., 2008). Using SPR and ITC in conjunction with NMR or X-ray crystal structures Nordstrom et al. produced an in silico drug design based on the binding sites identified by the crystal structures, using pharmacophore properties to model a binding molecule. Mutant proteins were designed in silico and then generated, immobilised on chips along with wild type proteins as depicted in figure 14.   Molecules designed in silico could then be screened against the different p roteins on the chip. For screening purposes SPR is limited, the number of molecules screened against the biosensor is relatively small as the proteins become degraded; only a couple of hundred molecules can be screened, compared to thousands in HTS.   The library must therefore be carefully designed, using in silico modelling, docking and screening, or with a vast knowledge and understanding of the target. Alternatively, SPR can be used in hit validation for lead series initiation, assessing the enthalpy and kinetics of binding, as was the case for capstatin analogues to increase binding affinity for C3b in the treatment of multiple human disorders involving the over-activation of complement (Qu et al., 2010). C3b is an appropriate target because it is involved in so many disorders such as neurodegenerative, sepsis and has also been linked to stroke. Campstatin is a good peptidic protein inhibitor, binding and inhibiting C3b regardless of the initiation pathway. However, due to its peptidic nature, Campstatin is not very stable with a short half-life in vivo, and due to the low concentrations of C3b found in plasma, a higher affinity compound with better pharmacokinetic properties would be ideal. N-methylations were analysed at different positions on the Campstatin scaffold and changes in binding affinity measured using SPR, and confirmed using ITC to conclude that by generating a compound that retains a rigid structure both in solution and in a bound state, it would bind with increased enthalpy, without decreasing the entropy as had other previous designs (Qu et al., 2010). This demonstrates the powerful applications SPR and ITC can have in drug discovery or design, and how in conjunction with in-silico computer based techniques, they can complement X-ray crystallography and NMR techniques. 2.4 The Difficulties Associated with Membrane Protein – The B2 Adrenergic Receptor: an Example of A G-Protein Coupled Receptor Crystallisation seems to be at the heart of structural biology   and even with the option of NMR there are still severe limitations that mean many proteins, particularly membrane bound proteins, cannot be crystallised   and thus cannot be visualised as a 3D structure. This is particularly problematic for structure-based drug design, as some 50% of drugs target G-protein coupled receptors (GPCRs) alone, not including the many other families of membrane bound proteins.   GPCRs are a superfamily of proteins which all have 7 transmembrane helices found in eukaryotes important in many crucial signalling processes (Lundstrom, 2005). The problem with studying membrane proteins in general is the difficulties in solubilising them and getting enough protein to work with. To obtain this large amount of protein, recombinant protein is required and for human protein this is a particularly difficult task (Mancia et al., 2007). The lack of structural information limits our understanding of ligand binding, as well as allosteric control and active site location (Summers, 2010).   There have been major advances in obtaining the structures of GPCRs recently, with structural information on rhodopsin, A2A adenosine receptor, B1 adrenoreceptor and the B2 adrenergic receptor.   The problems to overcome were obtaining enough usable protein, thus an appropriate expression system, the intrinsic flexibility and therefore excessive instability, and obtaining the exact solubilising formula for each protein. Once achieved, the crystallisation process for membrane proteins is no different than for globular proteins (Velipekka et al, 2010). To stabilise the different GPCRs, mutagenesis was used in rounds for B1 adrenoreceptor (Warne et al., 2008), or in the case of the B2 adrenergic receptor and A2A adenosine receptor, the flexible intracellular loops were stabilised by replacing them with the easily crystallised and inherently stable T4 lysozyme (Rosenbaum et al., 2007). Therapeutics aimed at A2A adenosine receptor could help in the treatment of seizure, asthma, Parkinson’s, pain and many other neurological problems (Jaakola et al., 2009). The crystal structure of the A2A adenosine receptor with the antagonist ZM241385 enabled the determination of important residues in ligand binding, and thus generated the information required to use computational modelling studies to suggest residues that would be important in inhibitor binding. Figure 15 depicts the binding of the antagonist, hydrogen bonded to Asn253, aromatically stacked against Phe168 as well as hydrophibically interacting with Ile274. An understanding of these interactions greatly helps in the elucidation of therapeutically important binding molecules ( Jaakola et al., 2009). B2 adrenergic receptors, a class of GPCR are important in smooth muscle related diseases such as asthma (Cherezov et al., 2007). Cherezoc et al. made a B2-adrenergic receptor T4 lysozyme fusion protein to enable crystallisation with Carazolol at 2.4Ã…. Carazaole has high affinity for the receptor, lying adjacent to, and making significant interaction with the residues Phy289, phe290 and Trp286 as seen in figure 16b and reduces basal level of activity of the receptor via its interactions with phe289/290 which result in the inactive trp286 state as seen in figure 16. This understanding of agonist binding and an in depth knowledge of the residues involved, if expanded upon could increase the possibilities for structure-based drug design and modelling. 3. Conclusion 3.1 Summary of Main Points and Advantages of Structure-Based Techniques The power of structural biology is apparent; it provides a clear physical picture of the target protein. It enables the identification of hit compounds via X-ray crystallography and more commonly NMR, supported by the complimentary techniques – computational analysis, SPR, ITC and DSF. Such techniques can validate those hit compounds to enter them into lead series and they can then be used to optimise leads to generate clinically usable compounds. The importance of structural biology is therefore easy to see as it has been successful in generating clinically used drugs, Darunavir for the treatment of HIV as a protease inhibitor being just one of many examples. 3.2 The Limitations of Structure-Based Techniques Of course they are not without their limitations. X-ray crystal structures are static freeze frame shots of a dynamic system, so we cannot be certain that what we see is biologically relevant or simply artefacts. Both X-ray crystallography and NMR suffer with the inherent instability and flexibility of proteins. There are methods to improve the 3D structures, as seen in the crystallisation of membrane protein – the B2 adrenergic receptor (Rosenbaum et al., 2007), suggesting that these limitations are not permanent, and can be overcome. Many proteins cannot be crystallised, and though there has been recent breakthroughs as with the case of the GPCRs, the vast majority have not been visualised and yet 50% of drugs are aimed at them. Complementary techniques such as SPR, ITC and DSF have successfully been used to identify hit molecules (Nordstrà ¶m et al., 2008) and to validate or optimise leads (Huber, 2005). Unfortunately these too are not without their faults, requiring smaller screening libraries, and the proteins involved to be constantly replaced during screens. To overcome this there have been computer based in-silico screening and design processes, which under certain circumstances has been used efficiently as was the case with the optimization of Darunavir (Ghosh et al., 2011), however there have been huge limitations. The first human GPCR crystallised, rhodopsin was a model for all GPCRs and in-silico modelling studies utilised it to generate binding molecules, but with the visualisation of the A2A adenosine receptor via X-ray crystal images, it became apparent that this was a far too over-simplified view ( Jaakola et al., 2009). 3.3 Concluding Thoughts and Future Advances To conclude, there are clear limitations concerning the structure-based design of therapeutic drugs, requiring further advances in technology and understanding to be made before we can easily utilise every form of technology efficiently and in an integrated fashion. Structure-based techniques do not speed up the process of drug discovery, however, there are also clear advances that have been made through the use of such structural biology techniques. They should therefore continue to be used in conjunction with current technologies to ever improve the therapeutics in use. Future advances should include improved recombinant protein technologies and purification procedures to obtain the large quantities of protein required, improved detergent mixtures for membrane proteins as well as better crystallisation procedures in general to increase resolution. As well as finding hits for lead series of molecules, structural techniques should also focus on increasing the number of targets, so that whole new sets of drugs can be made to add to combinatorial drug therapies such as HAART in the treatment of HIV, in an attempt to overcome the problems of resistance.

STRATEGIC FINANCIAL MANAGEMENT Term Paper Example | Topics and Well Written Essays - 1250 words

STRATEGIC FINANCIAL MANAGEMENT - Term Paper Example Countless NPOs, in some countries referred to as NGOs, work for various causes and spend their entire fortune on their causes. Such organizations may include SOS Home Villages, UNESCO, UNICEF, World Wide Fund for Nature (WWF), Red Cross organizations, and many others (Rottman, 2012a). Similar to these organizations is another one known as the United Services Organization (USO). The USO is an American organization committed to the morale boosting and the spiritual enhancements of the American troops and their respective families all over the world. It is an organization which supports and aids the US troops spiritually. This organization serves the US troops in nearly 14 countries worldwide, 27 states nationwide, with nearly 250,000 volunteers working hard in 160 centers worldwide (Howell, 2011). Ethical Significance Considering the ethical and moral values of the USO, we will find a very strict policy regarding the organization’s mission statement and conduct. The USO was form ed back in 1941 during the Second World War, bringing the nation together to boost the morale of the American troops. It did the same during the Vietnam War and is continuing to do so in the war in Iraq and Afghanistan. The USO also serves for the medication and rehabilitation of all those injured soldiers who lost their vital body parts. The ethical values of the volunteers in this organization are extremely strict. They have a set of rules or a mission statement which must be followed. They include Do the Right Thing, Respect, Collaboration, Excellence, Accountability, Gratitude and Innovation. Working in the jurisdiction of USO, a volunteer must follow these principles. In return, volunteers are provided with various gifts according to the USO policy. These policies are very similar to those of every other functional NGO, as all these organizations have strict moral and ethical guidelines which a volunteer has to follow. The volunteers are not given any financial advantage, but t he volunteership provides them with various gifts and invaluable credits (Rottman, 2012b). Capital Budgeting With such an inflow of donations and funds from different organizations to USO, these funds must be spent in a proper budgeted manner in various fields. According to the financial statement of the USO, there have been total expenses of nearly $300 million by the 31st of December of 2011. The expenses of various processes of the USO are determined (Howell, 2011). According to their expenditure statistics, almost $228 million were spent on contribution of materials, facilities and services. This is the largest proportion of expenditures for the USO, which mainly includes medical support for all injured troops and facilities provided to various troops during their operations at the camps. After these expenditures, come the maintenance programs of various USO camps throughout the world, which required a budget of nearly $33 million in 2011. These expenditures include all maintena nce and day-to-day office work charges, which each camp particularly requires. Other than these expenditures, $35 million were nearly spent on various programs the USO conducted: the camp shows for the entertainment of troops, and the general public awareness programs, for which the USO pays to create awareness in the

Mesoamerican culture Essay Example | Topics and Well Written Essays - 750 words

Mesoamerican culture - Essay Example Over countless years, the Mesoamericans designed their beliefs and customs of life. This accumulation of millennia of proficiencies could be what permits Mesoamerican concepts to live on today. This paper will explain the aspects of Mesoamerica still manifest in present say Mexico Culture. One of the major aspects of the Mesoamerican culture that has been retained is the calendrical system. Some of the different types of the calendars that have been maintained is 260-day cycle, 360 and 365 days cycles of the year. Names that are given to different months, and years emanates from animals, flowers or even heavenly bodies. In addition, another aspect of Mesoamerican culture that exists up-to-date is Mesoamerican script. These include logosyllabic which is the combination of logograms and syllabary. The scripts are referred to as hieroglyphic. People can learn about the environment via Mesoamerican language. The observable fact of ethnic blend and de-Indianization is not happening homoge neously all over Mexico and the communal organization has permitted Indian personalities to keep art in particular zones, and has resulted in preservation of culture. Hence, the continuance of biological indigenous qualities permits for continuance of Mesoamerican tradition and culture through language (Coe 16). Mexico does not bear an assorted mode of life. Diverse regions have dissimilar values, and much further, cultures in any area cannot be oversimplified; Indians still subsist and some have been chased out of Mexico. Non-Indian communities are not standardized either. Â  Country peasant communities are in existence and bear an Indian culture, however they lost the distinctiveness that runs with it. Farming ideas, philosophies about the ecological realm and Indian systems of eating and designing they still manifest in Mexico. Nevertheless, communal association in the farming world is somewhat altered. The farmers still execute matters in the Indian manner; nevertheless, they n o longer see themselves as Indians Coe 46). The essence of community inside the Oaxacan hamlet of San Andres is incredibly striking. The community functions together in countless distinct ways. A structure of titled 'tequio' runs as a consolidating body. Every family in the community has a responsibility to aid work and give a fee to the tequio. The tequio convenes monthly to perform stated developments that help the village or a commune member. It strengthens unity and functions as the community authority. Due to reliance on one another, the Chicahuaxtla community remains strong. Additional activity that fortifies the commune goes down annually- the entire community marches around the frontiers of the village. This aids to evade conflicts with neighboring communities by commencing peaceful relations. The Tequio structure, annual feasts and collective dances, ceremonies all add to and refurbish the distinctiveness of the communal. Various affiliates of the communal might not be cons cious of the implication of their everyday actions in the culture conservation. Actions are simply understood as rewarding a pledge or entertainment (Dierhl 45). Conclusively, most Mexicans are pondered believed to be Catholic however, in Mexico Catholicism assumes a distinctive custom different from the

History of Project Development

History of Project Development A project is a temporary endeavor to create a unique product, service or result. The temporary nature of projects creates a defining beginning and end. Project management is the application of knowledge, skills and tools and techniques to project activities to meet the project requirement. Project is accomplished through appropriate application and integration of different process groups. A project fills an essential need in society. Indeed, projects are the major mode in which change is accomplished. It is the mode in which corporate strategy is implemented, business change is addressed, productive teams and their necessary competencies are dealt with, quality of deliverables, and tracking pre-established metrics for managements decision making, as well as closing out a project and creating lessons learned are performed. Historical Developments on project management Pre 1950 Era The project management is now in its modern form. There has been some form of projects since early civilization. The hard system approach which treated the project as mechanical activity has shown to be flawed. Earlier endeavors were seen as acts of worship, engineering or nation building. And the people controlling the Endeavour saw themselves as members of groups focused on specific calling such as generals, priests and architects. Examples of such endeavors are the Great Pyramids and the construction of the Great Wall of China. Small and large scale projects were undertaken before the 1950. Near the turn of 20th century Fredrick Taylor known as the Father of Scientific Management began his detailed studies in 1856-1915. He applied scientific reasoning to work by showing that labor can be analyzed and improved by focusing on its elementary parts. Another one of the forefathers of project management was Henry Gantt who is best known for creating his self named scheduling diagram, th e Gantt chart. It was a unique idea and innovation at that time. One of its first applications was on the Hoover Dam project which started in 1931. Gantt diagrams are today an important toolkit for the project managers. 1950s Era The nature of project management was evolved during the 1950s. Formal tools and techniques were developed to help managers manage large and complex projects that were uncertain and risky. Early practitioners of project mangers and the associated specialties of planning, scheduling, cost estimating, cost and schedule control formed during the AACE in 1956. In 1957, the chemical manufacturer developed the Critical Path Analysis (CPM) method for predicting, scheduling, and sequencing of activities in logical order. Furthermore, DuPont designed it to address the complex process of shutting down chemical plants for maintenance and then with maintenance completed restarting them. In 1958 the United States Departments US navy special projects developed PERT as a part of planning Ballistic missile development. PERT is a method used for analyzing the tasks involved in completing a project and especially the time needed to complete each task and identifying the minimum time needed to complete the total project. The United States department of defense created the Work Break down Structure Concept as a part of the Polaris mobile submarine launched ballistic missile project. The work breakdown structure remains one of the most effective project management tools. It helps in organizing and defining total scope of the project and as well as represent the work specified in current approved project scope statement. In 1965 The International Project Management Association (IPMA) was founded. It was the world first project management Association. Its vision is to promote project management and lead development of the profession. In 1969 PMI was founded to promote and support project management profession. Beginning in 1981, the Project Management Institute (PMI) took formal steps to accumulate and codify relevant knowledge by initiating the development of what became their Project Management Body of Knowledge (PMBOK). The perceived need to do so arose from the PMIs long-term commitment to the professionalization of project management. ` The PMI book was an attempt to document and standardize accepted project information and practices. The first edition was established in 1996 followed second edition in 2000, and third edition in 2004. In 1989 PRINCE method was published by CCTA. Project IN Controlled Environment (PRINCE) became the UK standard for managing all government system projects. 1990 -2008 Era In 1996, PRINCE2 was published by CCTA (Projects IN Controlled Environments) and it is a structured method for managing small and large projects. It is the accepted standard for the UK governments Central Computer and Telecommunications Agency (CCTA) and was revised in1996.As a standard for project management; it is widely used in the IT industry and is finding application in other sectors. In 1986 Theory of Constraints (TOC) was introduced by Dr. Eliyahu M Goldratt in his Novel The Goal. TOC is an overall management philosophy that is geared to help the organization to achieve their goal. The methods and algorithms from TOC went on to form the basis of Critical Chain Project Management. Also the critical chain project method is helpful in resource leveling and it focus is on managing resources that are required to execute the project. In 1998, PMBOK became well recognized by the American National Standard Institute and as well as by Institute of Electrical and Electronic Engineers. In 2006, Total Cost of Management Framework was released by AACE International. It is the process for applying the skills and knowledge of cost of engineering. Up to 2008 PMBOK is the recognized standard for the project management profession. A standard is formal document that has described and established norms, methods and processes and practices. The knowledge contained in this standard evolved from the recognized good practices of project management practitioners who contributed to develop the standard. Present In its 50th year, the profession of ‘modern project management is facing many challenges and opportunities. The boundaries of our technology are merging into a range of other disciplines including communications, general management and corporate governance and arguably everything could be a project. One dimension of the challenges faced by the profession of project management is defined by its success. Almost every organization wants to be seen to be ‘doing projects. Projects are viewed as an important part of their endeavors to remain competitive in rapidly changing world. Project management is now an advanced and specialized branch of management. At this stage, project management emphasizes on the strategic role of projects, especially those processes that the project manager must put in place to deliver the end objective of the project and satisfy the needs of all the projects customers. In this new approach, project managers become project integrators, responsible for integrating the required resources, knowledge, and processes from the projects beginning to end. In particular, the ready availability of technology (especially communications technology) has led to the emergence of virtual teams as a means of running projects. Similarly, there has been considerable development of powerful project planning and software and the computer processing power to support it. Both of these have the potential to change the way that we work in projects. Furthermore role of project manager has significantly changed over the couple of decades. The project manager is the person assigned by the performing organization to achieve the project objectives. He is responsible for monitoring and coordinating activities throughout the organization. As in order to stay alive in the cut throat competition manager needs to be proactive and think strategically. It is the great responsibility of project managers to ensure quality of deliverables of the project. He must look and seek opportunities from the market demand. He must identify the weak links and identify all possible constraints that result in delay of project deliverables. Furthermore project managers must have area specific skills and general management proficiencies that are required for the timely and quality deliverables of the project. Future Challenges The future of project management is predicted to be one that focuses on the skills needed to motivate, direct and lead the people that make up the project team to achieve the projects goal whilst realizing the fact that nothing is certain. The competent project manager will be expecting uncertainty and will ensure his project management systems to provide as much early warning as possible of impending changes so as to give maximum possible time to optimize results and achieve stated objectives. Tools such as the project schedule will need to be predictive and help in pro-active decision making rather than reactive. The key skill set of the competent project manager will be identifying and managing stakeholder expectations. The purpose of documents such as project schedules and cost plans will be redefined from ‘control documents to ‘communication documents. The paradox is that by dropping the false expectation of control and certainty, the skilled project managers are lik ely to consistently deliver more predictable and reliable project outcomes. In summary, all the main issues faced by project managers are as follows: Strategy In future, the role of strategy will be more explicitly recognized by organizations, resulting in an increase in the use of devices such as the aggregate project plan. This will reduce conflict within and between organizations. Structure At present it is common for organizations to fail to balance the importance of a project with the structure used for it. As project management asserts itself as of importance within organizations, more appropriate structures will be used. Furthermore, organizations will have to begin working outside the existing structures using hybrids and new structures of their own to achieve their objectives. Systems we will continue to see an increase in the visibility of project systems, with visual control being the driver. There is a challenge for IT providers to produce project management software that will help this process. Staff- the selection of staff for projects needs to be more objectively managed. The tools and techniques are available. Skills the skills of the project manager are likely to increase in value. In many industries, people are given project responsibility because of their technical competence in one or more disciplines. In future, the skill-set of the project manager will become better recognized and valued by organizations. Style/culture this has been used by many organizations as a reason for not making any changes in the way they do their work. It is vital that in future, managers take responsibility for the culture that they create around them and for their own style. Awareness of this should be routine. As for staff selection, there are well-developed tool and techniques for managers to use in this respect (e.g. through cultural audit). Their application will increase with the passage of time. Stakeholders The marketing of achievements to stakeholders is in its relative infancy. This improved management of the information that stakeholders have is an important area in which project managers will need to work alongside their marketing colleagues. One further issue concerns all the above and that is learning. Organizations and individuals in many roles, not just project managers, are generally poor at learning from their own successes and failures, but particularly bad at learning from the successes and failures of others. It is a fact that those organizations that learn the fastest are also the best. The major challenge for project managers is to develop the process (do it better next time) by bringing in the necessary knowledge (both managerial and technical). All the issues from the 7-S given above provide potential areas for improvement. Part of the skill of the project manager is going to be identifying where the major benefits will be gained and the changes that will be needed to realize them. This will require a very wide knowledge of both theoretical and practical aspects of project management.