Marketing Plan of Thy free essay sample

With a populace of 75 million, a unique economy, a moderately huge geological region (780,000 sq km) and expanding discretionary cashflow among its population,Turkey’s air head out interest keeps on developing, when most of Europe is encountering sharp decreases. 1. 2 Strategic geographic position: The nation is appealingly geologically situated, found just three hours flight time from 50 distinct nations (as indicated by Turkish Airlines) and its one of a kind position. 1. 3 Strong local nearness: Turkish Airlines at present works to 37 local goals. . 4Star Allianceâ membership and cozy relationship with Lufthansa: Most aircrafts should be a piece of a coalition so as to get by later on supposing that you are not an individual from a collusion it is exceptionally difficult to rival different unions that offer mind boggling benefits 2. Outer examination. 2. 1 Political factor THY is an administration claimed, national banner bearer Labor understanding has powerful(Turkish Civ il Union of Aviation) Discounters suit themselves and bring in cash from receipts on account of guidelines of government In 2002, the new Turkish Government declared, it would not be appropriation for THY The State Privatization Administration propelled an open offer contribution Trust of money related markets without the requirement for government ensures 2. We will compose a custom article test on Showcasing Plan of Thy or on the other hand any comparative subject explicitly for you Don't WasteYour Time Recruit WRITER Just 13.90/page 2 Economical factor Ticket costs have risen in light of the expanding in fuel costs Air travel in Turkey will be the greatest development advertise THY sells tickets through the Internet with the goal that business expenses can be limited The quantity of aircraft organizations will be lessened and the state of market will change since carrier firms in Europe fortificates The quantity of heading out visitor from Europe to Turkey chop down because of the fear mongering International monetary situation,or worldwide emergency 2. 3 Social factor In universal region, contenders use administration culture enough to make their clients agreeable about the carrier They have consistently been exchange situated, not client arranged Swine flu,climate conditions and crash in Amsterdam People’s way of life of transportation is changed by advancement in airplanes Service culture issue, It will require some investment Special days . 4 Technological factor Satellite programming, remote web get to, satellite screens at each seat and seat â€back individual video screens in modish airplanes Reservation on phone and on the Internet THY utilizes IBM PCs Turkish Airlines (THY), to produce results the new serious conditions on the planet, which has become a significant reality, â€Å"On-Demand Enterprise† business forms so as to become in-house, it heard the requirement for adaptability for offices inside the system of between and clients. This is in accordance with the administration of programming improvement, foundation, procedures and instruments expected to standard. 2. x. Coment We did interior and outer examination. It gave to see device to review and investigation of the general vital situation of the business and its condition for us. it is the establishment for assessing the inside potential and confinements and the plausible/likely chances and dangers from the outside condition. It sees all positive and negative factors inside and outside the firm that influence the achievement. 3. Swot examination. Qualities |OPPORTUNITIES | |Expanding home market economy and good segment; |A developing business sector, in spite of the financial emergency; | |Strategic geographic position; |A famous the travel industry goal; | |Substantial cost advantage over adversaries; | Profiting by progression approaches; | |Rising piece of the overall industry; |Extend inclusion to Transatlantics; | |Star Alliance enrollment and cozy relationship with Lufthansa; |Business clients center; | |Great flight recurrence; |Drawing travelers into ahead departures from Istanbul center; | |Great item and client administrations; | |WEAKNESSESS |THREATS | |Turkey |Currency movements may repress productivity; | |Higher hazard natural development system; |LCCs expanding their quality; | |Massive armada development to subsidize; |Lufthansa item separation; | |Under-using the capability of a solid collusion; |Lufthansa inclusion extension; | |Market adjustment item; | |Product separation; | |Brand/explicit item mindfulness; | II Stage Resarch examination market and client 1 Competitors Overview and Situation investigation Turkish Airlines rivals three primary carriers on the course London. Istanbul. Theseare: British Airways that execute departures from London Heathrow to Istanbul Ataturk (2-3 flightsdaily), Pegasus Airlines serving London Stansted Istanbul Sabiha Gokcen (1 flight daily)and Easyjet serving London Gatwick Istanbul Sabiha Gokcen (1 flight every day). Based onthe above data, Turkish Airlines primary contender is British Airways as a full serviceairline giving association from fundamental to-principle air terminal, while Pegasus Airlines and Easyjetare LCC executing departures from optional air terminals to Istanbul Sabiha Gokcen airportlocated further away from Istanbul in the Asian side. Turkish Airlines is the main companyserving air terminals as London Gatwick, London Stansted, Manchester and Birmingham inaddition to its primary London Heathrow base. 1. 1 The Competitors for Turkish Airlines are named direct and non-direct danger. In spite of the fact that BA is an immediate danger to Turkish Airlines, the last have the preferred position ofservicing various air terminals around UK, focusing on nearby networks and organizations on awider range 1. 1. 1. English Airways British Airways is the fundamental contender of Turkish Airlines on the course LHR-IST. It is a fullservice aircraft the national transporter of Great Britain. Its solid situation in the UK showcase iswell characterized. BA serves in excess of 680 goals around the globe some of which oncode share bases with One World accomplice carriers. 1. 1. 2 Pegasus Airlines Pegasus Airlines is a LCC adjusting London Stansted Istanbul Sabiha Gokcen Airport. Theairline isn't named a principle danger to Turkish Airlines benefits as it works fromsecondary air terminals and its item has a low worth contrasted with the full assistance of TurkishAirlines. One bit of leeway of this transporter is the way that it has broad course associations inregional Turkey. 1. 1. 3. Easyjet is a Low Cost bearer overhauling London Gatwick Istanbul Sabiha Gokcen Airport. The aircraft isn't delegated a fundamental danger to Turkish Airlines administrations, despite the fact that itoperates from the second biggest air terminal in London Gatwick. Its item has a low valuecompared to the full assistance of Turkish Airlines. The carrier is better situated with flightservices inside territory Europe and includes no local associations inside Turkey. 1. 2 Competitors items Pegasus Airlines and Easyjet, as minimal effort bearers have all around characterized item structure mainlytargeting the relaxation showcase. Their item esteem alludes to the minimal effort model with fewerservices ready - item that can for the most part be coordinated to explorers on a tight spending plan (no seatallocation, paid bites and stuff remittance, and so on ). Their flights are worked eitherfrom/or to optional air terminals which are no alluring to more extensive gathering of passengers(especially business). Thusly their item and advertising methodology varies from the one ofTurkish Airlines. English Airways is a full help carrier that give comparative item to Turkish Airlines andtherefore is considered as the primary contender. They give the economy (relaxation traveller)product alongside the upper economy and business class understanding. 2. Clients The essential objective market for the carrier is corporate business air travel. The primary need ofthis sort of clients is the corporate markdown accessible as a byproduct of volume. The companyproduct will be situated to these clients to give huge cost reserve funds overcompetitors. Both London and Istanbul are urban areas with numerous worldwide organizations andbusinesses, which make a tremendous market for corporate travel. Corporate voyagers that TurkishAirlines ought to target incorporate, Deutsche bank, PwC, Delloit, Shell and a few otherprominent partnerships with joins in Istanbul and London who fly business class and hassignificant volume of business travel between the pair urban communities. The auxiliary objective market for the carrier is the private company and free businesstravellers who regularly fly from Heathrow to Istanbul yet in addition from the mechanical urban communities Manchester and Birmingham. The item will be situated for these clients byproviding a FFP and a business class toll that is essentially lower than most traditionalfares (the two principle needs of business voyagers as per overviews). The item will alsobe situated to this objective market as the one with the most elevated levels of administration on board theaircraft, altogether more significant levels of solace offered by the seats and a further extent ofluxury contrasted with the opposition. The last objective market for the aircraft is the extravagance travel showcase that exists from London andManchester to Istanbul. The item will be showcased and situated to these clients as a „ five star administration at business class fares’ . These clients are commonly uninterested inthe recurrence requested by business explorers. III Stage Determine Segmentation system and situating . Target Positioning of Turkish Airlines The essential objective market for the carrier is corporate business air travel. The fundamental need of this sort of clients is the corporate markdown accessible as a byproduct of volume. The organization item will be situated to these clients to give huge cost reserve funds over contenders. Both London and Istanbul are urban areas with numerous global organizations and organizations, which make an immense market for corporate travel. Corporate travel

A Dolls House A Push to Freedom Essay Example For Students

A Dolls House: A Push to Freedom Essay At some point after the distribution of A Dolls House, Henrik Ibsen spokeat a gathering of the Norwegian Association for Womens Rights. He clarified tothe gathering, I should decay the respect of being said to have worked for theWomens Rights development. I am not even sure what Womens Rights are. Tome it has been an issue of human rights ( ). A Dolls House is ofteninterpreted by perusers, instructors, and pundits the same as an assault on chauvinisticbehavior and a weep for the acknowledgment of womens rights ( ). Rather its themeis indistinguishable from a few of his plays composed around a similar timespan: thecharacters readily exist in a circumstance of lie or deficient truth whichconceals strife and logical inconsistency ( ). In A Dolls House, Norasindependent nature is in logical inconsistency the domineering authority of Torvald. This contention is hidden by the way the two of them shroud their actual selves fromsociety, one another, and eventually themselves. Much the same as Nora and Torvald,every character in this play is caught in a circumstance of unturth. In Ghosts,the play Ibsen composed straightforwardly after A Dolls House, a similar clash is thebasis of the play. Since Mrs. Alving yields to her priests ethicalbombardment about her duties in marriage, she is compelled to disguise thetruth about her late spouses conduct ( ). Like A Dolls House, Ghostscan be misconstrued as just an assault on the strict estimations of Ibsenssociety. While this is positively a significant part of the play, it is not,however, Ibsens primary concern. A Dolls House set a trend for Ghosts andthe plays Ibsen would send in following years. It built up a technique hewould use to pass on his perspectives about singularity and the quest for socialfreedom. The characters of A Dolls House show Henrik Ibsens conviction thatalthough individuals have a characteristic aching for opportunity, they regularly don't act uponthis want until an individual or occasion compels them to do as such. Perusers can rush to bring up that Noras change was slow andmarked by a few occurrences. An increasingly basic look uncovers these slow changesare really not changes by any stretch of the imagination, yet little disclosures for the peruser to seeNoras genuine autonomous nature. These occurrences additionally permit the peruser to seethis nature has been tucked far under a veneer of an upbeat and straightforward spouse. Inthe first act, she admits to Christine that she will move and spruce up andplay the moron to keep Torvald upbeat ( ). This was Ibsens method of telling thereader Nora had a shrouded character that was increasingly genuine and controlling. Hewants the peruser to understand that Nora was not simply the bonehead she permits to beseen as. Later in a similar demonstration, she shouts to Dr. Rank and Christine she hashad the most exceptional aching to state: Bloody Hell!' ( ). This longingis without a doubt emblematic of her aching to be out of the control of Torvald andso ciety. In spite of her longing for opportunity, Nora has, until the end of the story,accepted the solace and straightforwardness, just as the limitations, of Torvalds homeinstead of confronting the rigors that go with autonomy. Ibsen needed thereader to get a handle on one thing in the primary demonstration: Nora was happy to trade herfreedom for the simple existence of the doll house. Ibsen shows that it takes a sensational occasion to cause an individual toreevaluate to what degree he can forfeit his actual human instinct. For Nora,this occasion comes as her acknowledgment that Torvald esteems his ownsocial status above affection ( ). It is imperative to comprehend Nora doesn't leaveTorvald on account of the deigning disposition he has towards her. That was, inher eyes, a little cost to pay for the solace and soundness of his home. InBernard Shaws exposition on A Dolls House, he communicates that the peak of theplay happens when the womans eyes are opened; and immediately her dolls dress isthrown off and her better half is left gazing at her( ). To the peruser it isclear that Helmer is brought to his detects when his family starts to fallapart ( ). It is significant that Shaws syntax isn't neglected. Thestatements the womans eyes are opened and Helmer is brought bothindicate that the subject of the announcement is

How Record $1.57 Trillion in Student Debt Threatens the Economy - OppLoans

How Record $1.57 Trillion in Student Debt Threatens the Economy - OppLoans How Record $1.57 Trillion in Student Debt Threatens the EconomyInside Subprime: March 26, 2019By Aubrey SitlerThe Federal Reserve reported that student debt across the country had reached a record $1.57 trillion at the end of 2018. That amount has more than doubled since the recession ended in June 2009, when outstanding student debt was a mere $675 billion.This amount of debt that has accumulated at an increasingly rapid pace nationwide could pose a problem for more than just the borrowers who owe it back: it could also threaten the U.S. economy on a larger level.“Over 90% of student loans are guaranteed by the U.S. Department of Education, meaning that if a recession causes a rise in youth unemployment and triggers mass defaults, this contingent liability could prove burdensome for the U.S. government budget,” explained Paul Della Guardia, economist at the Institute of International Finance in emailed correspondence with Bloomberg.This means that the U.S. Government has taken o n an immense risk in lending out such a huge amount of money to people for student loans at an unprecedented rate. If something happens to make people unable to pay that debt back on large scales, the government would be in trouble.Based on data from the U.S. Department of Education, over 2.7 million student loan borrowers currently owe more than $100,000 each. Of these, approximately 700,000 people owe $200,000 or more. The depth of this debt burden is alarming on individual and system-wide levels. For many, these amounts seem insurmountableâ€"and they may be, depending on their income levels.According to a Bloomberg analysis, one particular group of borrowers poses a significantly higher risk than others. Compared with everyone who has taken out student loans since the end of the recession, those who took out student loans in 2012 have the highest cumulative loss percentage. This means that, even when compared with students who have had similar amounts of time to pay back their lo ans, these students have struggled the most with paying back their loans. There are a number of reasons for this, but notably, most of these 2012 borrowers are now between 24-33 years old. Many of them started working when the economy was floundering. The unemployment rate was almost double what it is today, and many peopleâ€"especially those entering the labor market for the first timeâ€"struggled or even failed to find work in their desired fields or wages that met their financial needs. According to the Bureau of Labor Statistics, it also took three times longer on average to find a position in 2012 than it does today.Each of these issues has impacted this group of borrowers not only when they first started out in the job market, but also as they have continued working. If they couldn’t get jobs for several months and then ended up underemployed, that set up their career trajectories at a much later and lower level than they probably anticipated when taking out loans to attend school.The age of borrowers with outstanding student loan balances has also shifted over time. As of the 3rd quarter of 2018, borrowers aged 25 to 34 owed about $489 billion, while those aged 35 to 49 owed a whopping $530 billion. In this same time period, borrowers aged 50 and over owed $276.1 billion in federal student loans, marking a $28.8 billion or 11.6% increase since the same quarter one year earlier.The full impact of these shifts toward higher overall student loan debt nationwide and debt carried across longer periods of citizens’ lives remains to be seen.For more information on  payday loans, scams, and  cash advances  and  check out our  city and state financial guides  including  Florida,  Illinois,  Texas,  Washington D.C.  and more.Visit  OppLoans  on  YouTube  |  Facebook  |  Twitter  |  LinkedIn

John Winthrop And Ralph Waldo Emerson - 1876 Words

About a century ago, such scholar as Nietzsche disregarded the principles of modern â€Å"factualism†. Later on, Weber established the end of the era of generalists. One cannot but state extreme specialization and narrowly focused technical work to have changed certain visions into straight forward realities. Concerning this essay, it is mainly aimed at analyzing the sociological speculations of two outstanding thinkers John Winthrop and Ralph Waldo Emerson that, in view of widely-acknowledged scholars, reflect the state of public opinion even though they date back over two centuries; to be precise, the focus lies in comparing and contrasting the utopian visions of the two above mentioned thinkers, making emphasis on what utopia meant for these two authors and the way it was supposed to be achieved. Moreover, the paper is focused on interpreting and coming to terms with the pivotal social movements of Puritanism as well as transcendentalism. Speaking about the peculiarities of social theories, it is necessary to take a view of recognized changes in vast domains of social life and culture. The research will emphasize the main reconstructions of social and cultural theories due to historical events. The essay is also targeted on finding out whether it is logically to discount all the concepts, methods of the past, and acknowledge the new theoretical assumptions. According to Kathleen M. Hogan of the University of Virginia, the historical yearning for some type of American utopiaShow MoreRelatedRalph Waldo Emerson, John Winthrop, And Benjamin Franklin1297 Words   |  6 Pagestopic are Ralph Waldo Emerson, John Winthrop, and Benjamin Franklin. Each author has a different view over this subject. Emerson believes someone should not conform to his or her society, while Winthrop believes conformity is what will benefit society; Franklin on the other hand believes in a mix of both. Between all three, Franklin’s idea of a fusion between Emerson’s and Winthrop’s ideal modes of life is the proper balance to create a efficient and affective society. In Ralph Waldo Emerson’sRead More`` Contemplations `` By Anne Bradstreet Essay1462 Words   |  6 Pagesthe â€Å"manager of the country estate of the Puritan Earl of Lincoln†. At the tender age of sixteen, Anne met Simon Bradstreet, a man who shared the same Puritan ideals as her father. They were soon married and set off for the New World, along with â€Å"Winthrop s fleet† among the Massachusetts Bay Company. Life in America was not an easy existence for most, however proved especially difficult for Anne Bradstreet. The wilderness was particularly brawny, especially when juxtaposed against Bradford’s nearlyRead MoreThe Influence Of Calvinist Ideas On The Early Nineteenth Century900 Words   |  4 Pagesideologies that were brought upon by the puritans. Calvinism, which was based on the teachings of John Calvin, emphasizes predestination and salvation because a man had no free will and thus dependent of God, man had no control over his own spiritual fate, hence their over all actions in life. (Garcia, Lecture 2, p.2) However, John Winthrop, a puritan lawyer of the time, and others criticized this idea, Winthrop discussed the issues with these ideologies, absence in individual freedom lead to a hopelessRead MoreThe Evolution of American Literature637 Words   |  3 PagesThe Evolution of American Literature Early American literature may be said to begin with the Colonial period. John Smith and John Winthrop are two examples of the types of writing at this period: the former kept a romantic journal of his adventures in the New World; the latter kept a journal (or history) of life in New England, where religious matters were of utmost importance. The Puritans had come seeking a life free from religious persecution (which, they ironically brought with them howeverRead MoreThe Declaration Of Independence By Thomas Jefferson And Models Of Christianity1720 Words   |  7 PagesAmericans. Some of these philosophies and ideas are still valued today, but others have lost value with the development of society. The two articles â€Å"The Declaration of Independence† by Thomas Jefferson and â€Å"Models of Christianity† written by John Winthrop will describe how some social interactions have changed such as religion, and others have stayed the same such as life, liberty and the pursu it of happiness. Religion helped early settlers become a unified society in early America. People whoRead MoreHester Prynne and Roger Chillingworth in Puritan Society Essay1208 Words   |  5 PagesBelieved by many writers such as Ralph Waldo Emerson, society corrupts and conforms the individual, and it is the individual who breaks from consistency and conformity that is most free. Hester Prynne, a woman punished for adultery, is isolated by herself and her community, but breaks free from strict Puritan society. Roger Chillingworth, the husband of Hester, isolates himself which leads to the destruction of himself and the community. Hester Prynne and Roger Chillingworth experience differentRead More1.) What Principles Do Franklin And Thoreau Propose For1340 Words   |  6 Pages1.) What principles do Franklin and Thoreau propose for the conduct of life? To what extent do their principles agree? Benjamin Franklin and Ralph Waldo Emerson propose certain principles for the conduct of life. Franklin is very clear in his proposed principles for life, as he clearly states them in his â€Å"The Autobiography of Benjamin Franklin†. One of his main principles is the concept of hard work. Franklin believes that the best way to succeed in life is to work hard. Hard work is a key elementRead MoreBrief Survey of American Literature3339 Words   |  14 PagesAmerican / American Indian oral literature / oral tradition creation storiesï ¼Ë†Ã¨ µ ·Ã¦ º Ã§ ¥Å¾Ã¨ ¯ Ã¯ ¼â€° trickster talesï ¼Ë†Ã¦  ¶Ã¤ ½Å"å‰ §Ã¨â‚¬â€¦Ã¤ ¼  Ã¥ ¥â€¡Ã¯ ¼â€° rituals / ceremoniesï ¼Ë†Ã¥â€¦ ¸Ã¤ » ªÃ¯ ¼â€° songs / chantsï ¼Ë†Ã¦â€º ²Ã¨ ¯ Ã¯ ¼â€° Anglo Settlers’ Writings Highly religious and pragmatic - John Smith, founder of Jamestown, Virginia; Pocahontas - John Winthrop, â€Å"A Model of Christian Charity†: â€Å"†¦ We shall be as a city upon a hill. The eyes of all people are upon us†¦Ã¢â‚¬  - William Bradford, Of Plymouth Plantation (1630-50, pub. 1856) - Anne Bradstreet (1612-1672), TheRead MoreNathaniel Hawthorne: Literature of Consience Essay2942 Words   |  12 Pagesauthors. nbsp;nbsp;nbsp;nbsp;nbsp;The Hawthornes had already left their legacy with the town of Salem leaving Nathaniel Hawthorne a long rich history of ancestry in the town. In 1630, William Hawthorne made the Journey to the New World with John Winthrop, the first governor of Massachusetts. Two of Hawthorne’s relatives who were directly involved with the Salem witch trials, also left their mark on the town. Hawthorne carried a direct relation to Judge Hathorne himself, being the primary causeRead More Puritanism: The People, Religion, and Poetry Essay4374 Words   |  18 Pageslike the biblical nation of Israel and as the body of Christ. For the Puritans, the importance of community related also to their self-perception as a covenantal people, like Israel. â€Å"For wee must Consider that wee shall be as a Citty vpon a Hill† (Winthrop). In some sense, they were separate; however, they borrowed intellectual traditions from history and England and strongly influenced the traditi ons through American history. Though Puritans highly valued community, the spiritual entitlement given

Nature Vs Nurture Essay - 1023 Words

For centuries, criminologists and scholars alike have explored different theories to help determine what causes one to engage in deviant behavior. In this paper, I will discuss one of the longest standing criminological disputes, nature versus nurture. After describing both theories in detail, I will determine whether I believe our intelligence, behaviors, and personality traits are genetically predetermined or if they are a product of our environment and the way in which we were raised. Science has proven that certain physical characteristics, such as hair color, eye color, height, and skin tone, are undoubtedly, genetically determined. Supporters of the nature theory, also known as nativists, argue that genetics and biology influence†¦show more content†¦These and several other studies alike revealed a positive correlation between low IQ scores and deviant behavior. While supporters of the nurture theory, also known as empiricists, do not fully discount the biological bel iefs of nativists, they argue that personality and intelligence is primarily sociological. In other words, people come into this world as a tabula rasa, or blank slate, and environmental influences and socialization are the most important factors in determining who we are and how we behave (Crossman, 2016). Nativists discredit the notion that people commit crimes because they have low IQs. Instead, they believe that environmental stimulation from parents, relatives, social contacts, schools, peer groups, and innumerable others create a child’s IQ level and that low IQs result from an environment that also encourages delinquent and criminal behavior (Siegel, 2018). Put simply, low IQ scores reflect a criminal’s cultural background, not their mental capacity. Examples of the empiricist perspective include John Bowlby s Theory of Attachment and Albert Bandura s Social Learning Theory. Bowlby’s theory suggests that children come into the world biologically pre-progr ammed to form attachments with others (McLeod, 2007). In his 1944 study on juvenile delinquents, he concluded that maternal separation early on in a child’s life causes permanent emotional damage. TheShow MoreRelatedNature vs. nurture Essay1322 Words   |  6 PagesNature vs. Nurture It is a matter of concern whether human behaviors and characteristics are determined by nature or nurture. If a person’s behavior is inherited directly from the genes of his/her parents or other biological factors, then it is the nature that determines his character. But if the environment that a person grew up in, affects his behavior, then it is the nurture that determines his/her character. It became a great matter of controversy among scientists, psychologists and sociologistsRead MoreNature Vs. Nurture Essay1612 Words   |  7 PagesNature vs. Nurture Essay Throughout many years, scientists have been debating about whether nature or nurture is the driving force that shapes a person’s cognitive abilities and personal traits. Before the ongoing debate can be explained, it is necessary to understand what nature and nurture actually are. Nature is loosely defined as the genetics one inherits and tendencies that influence development. Many things in an individual are hereditary, for instance; gender, disease, height, eye color,Read More Nature vs Nurture Essay804 Words   |  4 PagesNature vs Nurture In his book, the universally acclaimed and bestseller The Selfish Gene, Richard Dawkins presents his viewpoint that living organisms are but survival machines, that the individual [is a] selfish machine, programmed to do whatever is best for its gene as a whole. In fact, this is the central concept in his book that he brings across. An individuals behaviour and actions are 100% determined by its genes and the individual behaves in accordance to ensure the best persistenceRead More Nature vs Nurture Essay1585 Words   |  7 Pages Nature or Nurture? The Determination of Human Behaviour The nature versus nurture debate has spanned over decades, and is becoming more heated in the recent years. Following the mapping of the human genome, scientists are pursuing the possibility of controlling human behaviour such as homicidal tendencies or insanity through the manipulation of genes. Is this possible for us to ensure that humans behave in certain ways under certain circumstances in future? This is highly doubtful, as the determinationRead More Nature vs Nurture Essay570 Words   |  3 Pages Nature vs Nurture The issues pitting nature against nurture are exceptionally significant for the gamut of discoveries that attribute an increasing proportion of traits and behaviours to ones genetic makeup. The resulting variety of physical shortcomings and limitations in each person has, for centuries, been countered by endeavours to improve or interfere where necessary, and every individual is consequently the product of a delicate middle path of balance between the two. The importanceRead MoreNature vs. Nurture Essay794 Words   |  4 Pages Nature vs. Nurturenbsp;nbsp;nbsp;nbsp;nbsp; nbsp;nbsp;nbsp;nbsp;nbsp;Through time, psychologists have argued over whether only our genes control our behaviors in life or if the environment and the people surrounding us have any effect in our lives. This is called nature versus nurture. We do not know what dictates our behavior, or if it is a combination of both. One question is, if genes control our behavior, are we really responsible for our actions? I think that if we can make choicesRead MoreNature Vs Nurture Essay882 Words   |  4 PagesNature vs Nurture The discussion about nature and nurture can be considered one of the oldest problems in psychology, the main question of which is: Are human traits present at birth or are they developing through experience? (Meyers, 2013). The natural side of the discussion asserts that the facial features and the way of their development strictly through DNA and genetics are transmitted by parents and grandparents. The nurture side of the debate argues that we are born with a clean list andRead MoreNature vs. Nurture Essay1250 Words   |  5 PagesNature vs Nurture   Ã‚  Ã‚  Ã‚  Ã‚  For the past five weeks we have studied three different but influential people in our perspective on human nature class. They are Freud, Plato and Tzu. The main discussion between all of them is nature versus nurture. I will discuss the difference between nature and nurture and then I’ll apply to each of these philosophers and how they react to it.   Ã‚  Ã‚  Ã‚  Ã‚  When looked up in the dictionary the term nature means the universe and its phenomena or one’s own character and temperamentRead More Nature vs Nurture Essay778 Words   |  4 PagesNature vs Nurture Most of us have an intuition that, although our genes provide advantages and constraints, we retain great control over our lives. However, we are developing a second, competing intuition that, like it or not, our genes determine our abilities, our preferences, and our emotions. We would like to think we are much more than the sum of our genes, but scientists have apparently demonstrated that our genes determine some of our most complex behavioral and cognitive characteristicsRead MoreEssay on Nature vs Nurture1052 Words   |  5 PagesNature vs. Nurture M. B. Liberty University Psychology 101 Nature vs. Nurture There has been extensive debate between scholars in the field of psychology surrounding the Nature vs. Nurture issue. Both nature and nurture determine who we are and neither is solely independent of the other. â€Å"As the area of a rectangle is determined by its length and its width, so do biology and experience together create us.†(Myers, 2008, p. 8) Carl Gustav Jung, and leading thinker and creator of analytical

Educating Esme An Autobiography Of Esme Raji Codell s...

Educating Esmà © was a biography about Esmà © Raji Codell’s first year of teaching and the experiences she had throughout the year. She describes the many challenges faced when working in a school in a low income area and how it differs from that of a high income area. In addition, she talks about the many teaching styles and problem solving techniques she used in her classroom. Some of her methods she used were creative and could easily grasp the children’s attention, but one example of her style I would never use in my classroom is letting one of the children that repeatedly misbehaves teach the class. As a future high school teacher, I feel as if this particular method would be ineffective because of the age range of the children. However, I look up to her desire to educate children To begin, Educating Esmà © is an autobiography of Codell’s first year as a 5th grade teacher in a low-income school district. She talks about the many challenges she faced as a new teacher in a school where the children have a hard life than those with parents who have a higher income. She includes the fact that the children’s hone lives would sometimes spill over into the daily classroom setting. Throughout the book she tries to maintain a positive attitude towards the children, but she does not romanticize the hardships faced, and she does make the reader aware of how much of an emotional toll it takes on a person to teach a class. In addition, it is included of how she had problems with school

Traditional Forest Related Knowledge

Question: Discuss about the Traditional Forest Related Knowledge. Answer: Introduction: The Indian subcontinent is regarded as the great landmass of the South Asia. It is known as the home of the single most worlds ancient civilization and foremost influential. This subcontinent is usually regarded as India for historical purposes. It comprises of the area the present-day Republic of India and republic of Pakistan having been portioned from the India in the year 1947 as well as Bangladesh that made up the eastern region of Pakistan until 1971s independence. Right from the early period, the Indian subcontinent seemed to have offered attractive habitat for occupation by human. The Himalayas ranges to the north massively protected this subcontinent as well as sheltering it from the Arctic winds as well as air current of the Central Asia. Most of ancient contacts with the outside world occurred via northwest and northeast that were the solely regions easily accessed by land. The extensive alluvial plain of river basins offered environment and emphasized for rise of two significant stages of city life: the civilization of Indus valley called Indus civilization during third millennium BCE, along with during first millennium BCE, which of Ganges. The forest to the south of this zone separates India from peninsula proper. It runs generally from west to east which was inhabited by trial people. The region never formed a focal point of principal regional cultural development of South Asia and it remained thinly populated. The Indian forest offered home to the crores of individuals encompassing several scheduled tribes. These tribes dwelled in or nearby forest areas of India. These tribal communities showed a strong knit relationship with forests and dependent on such forests for existence and livelihood. Such association remained mutually beneficial. The rights of these tribal communities were never acknowledged by the civilization and they remained highly marginalized. They even had no right over the land as they were fully discriminated. Indeed, the forest dwellers were even not regarded or acknowledged as Indians. They struggled with modernity and civilization in a losing battle for the preservation of their identity. They were viewed as those cohort of families that had a shared tradition of shared descent, language and culture residing as close-knit community and held no private property. They were tainted by racist ethology that viewed them as primitive, barbarous groups and belonged to inferior races. All sorts of stereotyping was used when defining these forest dwellers coupled animism. This derogatory phrase was used during the early civilization to sideline the tribal religions. To date, this notion has stayed that such people are marginal to the mainstream society. The above notion of mainstream verses marginal duality marred the ancient Indian society. The system of caste advanced it individual classification, but the tribal remained unrecognized as sharply distinct from mainstream society. They were referred mainly as forest dwellers or the mountain dwellers but not tribe. As a result of the race-obsessed colonial ethnology, they coined Adivasi thereby labelling each Indian community as either Aryan or non-Aryan. However, India had no notion of original inhabitant that colonial powers had. Sociologist have helped that the notion of civilizers to regard certain tribe or the others as native owner of soil was utterly unscientific. Civilization coded the notion of how the Mahabharata list three-hundred and sixty three communities (jatis or janas) crossways the map based on the political, ecological or geographical terms some of whom have stayed recognizable as tribes like Mundas and Kokuratas. This notion is currently being decoded. The Epic never seemed to distinguish between tribe and caste with an exemption that the janas happed to reside in forests or mountains. There is however, barely evidence to showcase that in the shared consciousness of India, there is any distinction between the 2 sets of Janas. The janas list increases to about seven-hundred if all ancient literature is included. The forest tribes live in individual territory and were copious, valiant, fight in daylight as well as with the capability to seize along with ruin nations hence a notion of being behaving like kings. The atavika was coined to refer to tribe which is the forest dweller. The feared conquering impulse which paints a reflection of a historical fact that several tribes took to warfare, enlarged their territories as well as converted into as many Kshatriya clans. The mainstream Indias perception of her tribes stays blinkered by the colonial strategy, upon which missionary agenda rode piggyback, searching to detach substantial masses of non-Aryans. State Formation Process The ancient-formation in maritime Southeast Asia were Malaccra Straits alongside southern sea of Java shore. These were hub of wealth accumulation alongside trading activities along with shared various basic political concepts. Developments politically took place in the area owing to the reaction provided by the coastal communities to similar outside economic stimuli. The rising wealth in such 2 sub-regions was highly concentrated in hands of politically powerful elite that exerted control over prestige-good economies. The contacts with additional regions led to advancement I metallurgical techniques along with improved resource-base of the area for trade. The enlargement of economic bases of various trading communities together with escalated exposure to additional advanced political cultures. Culminated to the formation of a sequence, first of chiefdoms, and subsequently of nascent states, on appropriate coasts of peninsula as well as wester islands. The same case with Funan, that emerged on account of advanced traded along with port facilities due to the strategic location as well as backing by the agrarian base. Some have argued that it is rational to consider Funan as the 1st Southeast Asian state since it remained an economic hub, with the economic foundation which backed additionally sophisticated level of political integration while acting as locus of contact amid several regional alongside local marketing networks. Effects of State Formation Process on Tribe Cast Dynamics Relationship The pre-existing native cultural as well as ethnic diversity remained synthesized with the outside ideology to establish a novel systematic higher order cultural foundation. This is recorded in the rising utilization of Sanskrit in Funan, utilization of Indian vocabulary as well as technical knowledge. The Southeast Asian states borrowed primarily from vaster Indian religious traditions. This was in a manner which suggest that a self-conscious balancing of ideas thought to be useful for the upholding power in economies at once mercantile and agrarian. The habits in consumption shifted following Indian export thereby stimulating innovations in production locally. The cultural and religious influence was limited to rulers and elite sections of society hence never penetrated local levels. Therefore, economic competition as well as mutual impact instead of coerced contribution marred the relations between India and Southeast Asia thereby countering Indianization or colonization theory. Bibliography Avari, Burjor. India: The Ancient Past: A History of the Indian Subcontinent from C. 7000 BCE to CE 1200. Routledge, 2016. Ramakrishnan, P. S., K. S. Rao, U. M. Chandrashekara, N. Chhetri, H. K. Gupta, S. Patnaik, K. G. Saxena, and E. Sharma. "South Asia." In Traditional Forest-Related Knowledge, pp. 315-356. Springer Netherlands, 2012. Scott, James C. The art of not being governed: An anarchist history of upland Southeast Asia. Yale University Press, 2014. Thapar, Romila. The Penguin history of early India: from the origins to AD 1300. Penguin UK, 2015.

Materialism And Moral Hazard

To determine the effect of flowrate on rate of heat transfer Essays

To determine the effect of flowrate on rate of heat transfer Essays To determine the effect of flowrate on rate of heat transfer Essay To determine the effect of flowrate on rate of heat transfer Essay A concentric tube or double pipe heat exchanger is one that is composed of two circular tubes. One fluid flows in the inner tube, while the other fluid flows in the annular space between the two tubes. In counter flow, the two fluids flow in parallel, but opposite directions. In parallel-flow the two fluids flow in parallel and in the same direction.Fig. (1)PROCEDURE:The work was carried out the lower exchanger of a pair of concentric tube heat exchange. The lower exchanger had water passing through the inner tube, being heated by steam which flows into the outer tube and condenses. The condensate usually returns to the steam boiler, but there was a sampling facility so it may be collected and timed to determine condensate flowrate.The water to the lower exchanger was turned on and the flow was set to the desired rate. The condensate return line was checked if it was open to drain (floor),then the stem was turned on to the lower exchanger and the pressure was set at 10 psig.The system was allowed to reach study state (when outlet temperatures no longer vary), then the water temperature in and out of the lower exchanger was measured, the steam temperature, the condensate temperature, the water flowrate and the condensate flowrate. The condensate flowrate was determined by measuring the time of collection of a know volume of condensate.The procedure was carried out foe six different cold water flowrates over a wide range of values; for each run was ensured that the study state has been reached before taking readings.THEORY:A major resistance to heat transfer from the hot steam to the cold water is due a stagnant layer of steam and water on the surface on each side of metal wall of the inner tube. If the flowrate of the cold water is increased, the cold water becomes more turbulent and the stagnant layer on the cold water side of the inner becomes thinner, thus reducing its resistance to heat transfer.An energy balance shows that, at study state.-Loss of heat from the hot steam, Qh= gain of heat by the cold water, QcFor the water side:QC=mc.Cpc. (Tc out Tc in) (1)For the steam side:Qh =mh.?v+mh.Cph. (Ts-Th out) . (2)Where mh can be calculated from mh = Fh* ?cAnd mc = Fc * ?cSymbols:-Cpc= specific heat capacity of cold water, J/kg.KCph= specific heat capacity of hot condensate, J/chg.Fc = volumetric flowrate of cold water, m3/sFh = volumetric flowrate of hot condensate, m3/smc = mass flowrate of cold water, kg/smh = mass flowrate of hot condensate, kg/sQc = energy gained by cold water, J/sQh = energy lost by steam, J/sTc in = temperature of cold water enteringTs = temperature of steam entering exchanger, KTh out = temperature of hot condensate leaving exchanger, K?v = latent heat of vaporisation of steam, J/kg?c = density of cold water, kg/m3?h = density of hot condensate, kg/m3RESULTS:The results which took in the laboratory:RunsCold water flowrate (Litters/min)Steam in temp.Steam out temp.Could water in temp.(C)Co uld water out temp.(C)Condensate flowrate (millilitres/min)1171131120.74118001840221131120.784128036003151131120.74120401680451121110.763136012805101131120.74814401566CALCULATION:Note:Conversion:(Litters/min) = (0.001/60) (m3/s)(Millilitres/min) = (0.000001/60) (m3/s)C= 273 KData given:Cpc = 4180 J/kg.KCph = 4220 J/kg.k?v =2.22 * 106 J/kg.k?c = 996 Kg/m3?h = 958 Kg/m3Fc (m3/s)Fh (m3/s)mc (kg/s)mh (kg/s)Ts (K)Th out (K)Tc in (K)Tc out (K)Qc (J/s)Qh (J/s)%3.33E-050.0000220.03320.02107638638528035710685.7546877.66125.7462238.33E-050.0000220.0830.02107638538428033619428.6446877.6682.79460750.0001670.0000250.1660.0239538638528032128449.0853270.0760.7470570.000250.0000310.2490.02969838638528031435387.8866054.8960.46169070.0002833.03333E-050.28220.02905933338638528031440106.2664634.3546.835865* To worked out the value of Qc we used equation ( 1), but first we must got the value of mc from this equation :mc = Fc * ?cTo get values of Fc we convert the values of cold water flowrate from (Litt ers/min) to (m3/s), after we did all that steps we can work out the value of Qc easily. (As we know the value of ?c and Cpc given)Example: (I used the first run in this example):Fc = 17 * (0.001/60) = 0.000283 (m3/s)mc=0.000283 * 996= 0.2822 kg/sQc =0.2822 * 4180 (314 280) = 40106.26 J/s* To worked out the value of Qh we used equation (2), but we had first to got the value of mh from this equation:mh = Fh* ?cTo get value of Fh we took the average of the condensate floweate values and then we converted it from (millilitres/min) to (m3/s).Example: (I used the first run in this example):Fh = (1800+1840)/2 * (0.000001/60) = 3.03333E-05(m3/s)mh=3.03333E-05 * 958 = 0.029059333 kg/sQh = 0.029059333*2.22 * 106 + 0.029059333 * 996 (386 385) =64634.35 J/sDISSCUSSING THE RESULT CONCOLUTION:* When the flowrate is increased the % difference between the energy lost by steam and the energy gained by cold water will decrease.* The relation between Qc and Fc is direct proportion, therefore to tran sfer heat faster, we must increase the flowrate.* The value of the % difference in the first run is 125.7, which I think it is wrong and that happened because the flowarete value was too small, and that make the value of Qc small as well, therefore the difference is high.

Flash fiction exercise based on the prompts in the 'Rosemetal Press Assignment

Flash fiction exercise based on the prompts in the 'Rosemetal Press Field Guide...' - Assignment Example After twenty year, am sited at the old couch facing the ocean outside the cabin, it reminds me of the days we would spend the afternoons with my uncle after school, the holidays were even better as we would go fishing, hunting and gathering in the woods or just relax enjoying the cool breeze from the ocean. This is the place where I found real fun unlike in town, even when my dad came back, I continued living with my uncle until when I was to attend college, playing beach football with my friends from around is all I can remember, social life at the cabin was far much better than in town, I wish I could rewind the days, the cabin is empty as my uncle lost the battle to cancer. The brown faded couch reminds me of my active childhood that any young person would wish to have, it’s so sad I have to be away from the cabin to pursue my course at a college that is away from

Chevron Corporation Essay Example | Topics and Well Written Essays - 2000 words

Chevron Corporation - Essay Example Market Segmentation, by definition, is the grouping of customers into sub-units or segments based on their needs implying that a particular market segment has the same needs and as such, a business develops the same marketing strategy to respond to the needs. Segmentation of target markets takes three approaches namely undifferentiated, concentrated and differentiated. In this regard, undifferentiated segmentation entails a business treating customers as the same or when an organisation targets homogenous market while concentrated segmentation occurs when a firm focuses on several market segmentations that have same needs and preferences, for instance, price sensitive consumers. However, differentiated market segmentation entails a business targeting many market segments or heterogeneous markets as with the case of Chevron Corporation because it has various business segments. Chevron’s market segmentation depends on both the upstream and downstream business segments. Upstream business operations include exploration, development and production of natural gas as well as crude oil while downstream operations involve crude oil refinery, marketing in addition to the transportation of the finished or the final petroleum products.Nonetheless, businesses divide their market using demographics, psychographic, behavioural and geographic criteria when segmenting their markets. Demographic segmentation takes into consideration customer characteristics including gender, age, education, income status, cultural background and job.

Rapamycin And Cisplatin In Breast Cancers

Rapamycin And Cisplatin In Breast Cancers Recent gene expression profiling has identified five breast cancer subtypes, of which the basal-like breast cancers are the most aggressive and possess serious clinical challenges as there are currently no targeted therapies available. Although there is increasing evidence that these tumors confer specific sensitivity to cisplatin, its success is often compromised due to its dose-limiting nephrotoxicity and development of drug resistance. To overcome this limitation, our focus is to maximize the benefits associated with cisplatin therapy through drug combination strategies. Using a well-validated kinase inhibitors library, we showed that inhibition of mTOR, TGFà ¯Ã‚ Ã‚ ¢RI, NFà ¯Ã‚ Ã‚ «B, PI3K/AKT and MAPK pathway sensitized the basal-like MDA-MB-468 cells to cisplatin treatment. Further evaluation demonstrated that combination of mTOR inhibitor, rapamycin, and cisplatin generated significant drug synergism specifically in basal-like cells (MDA-MB-468, MDA-MB-231 and HCC1937). Th ese synergistic effects were not observed in the luminal-like T47D and MCF-7 cells. We further showed that the synergistic effects of rapamycin and cisplatin is mediated through p73. Treatment of rapamycin induced p73 upregulation and synergized cisplatin activity through activation of the p73 pathway. Depletion of endogenous p73 in basal-like cells abolished these synergistic effects suggesting that p73 is required for the rapamycin and cisplatin synergism. In conclusion, combination of mTOR inhibitors and cisplatin may be a useful therapeutic strategy in basal-like breast cancers. INTRODUCTION Recent identification of novel breast cancer subtypes with distinct biological features promises a more specific, effective and less toxic therapies to the patients. Through gene profiling, breast cancer can be categorized into five different subtypes with distinct clinical outcome. The five major subtypes of breast cancer are luminal A, luminal B, human epidermal growth factor receptor-2 (HER2) overexpressing, normal-like and basal-like breast cancer [1, 2]. Of particular important is the basal-like breast cancer which accounts for 15-20% of breast cancers overall and confers a remarkably poor prognosis compared to other subtypes. Majority of basal-like breast cancers exhibit a triple-negative phenotype, characterized by the lack of expression of estrogen receptor (ER), progesterone receptor (PR) or HER2 amplification, and often have high frequency of p53 mutation [3, 4]. Due to the lack of expression of these receptors (ER, PR and HER2), patients with basal-like breast cancers usua lly do not response to hormonal therapy, Herceptin or chemotherapy [5, 6]. As a consequence, the mortality rate of basal-like breast cancer is relatively high in comparison with the non-basal subtype [1]. Numerous clinical studies are currently ongoing to identify novel therapy for treatment of basal-like breast cancers. These include the use of specific targeted therapeutic agents (e.g. Cetuximab, Dasatinib, Bevacizumab, Abraxane and Erlotinib) or conventional chemotherapeutics agents (e.g. cisplatin, doxorubicin, and paclitaxel), either as single agent or in combination, as first line therapy for basal-like breast cancers [7-9]. Cisplatin, a chemotherapeutic agent not commonly used for breast cancer, come to light in the management of basal-like breast cancer on account of evidence that breast cancer cells with basal-like phenotype confer a selective sensitivity towards cisplatin as compared to other chemotherapeutic agents. A variety of evidence suggests that basal-like breast cancers may share defects in BRCA1-associated pathways, of which DNA repair mechanism has been compromised [10]. Indeed, recent clinical studies have demonstrated the clear advantage of cisplatin in treatment of basal-like breast cancer compared to other chemotherapeutic agents [11, 12]. Nevertheless, dose-limiting toxicity including nephrotoxicity, neurotoxicity and ototoxicity have withold the wide-spread use of cisplatin in treating breast cancers in the clinic. To address this problem, we developed a high-throughput screening assay to rapidly identify new therapeutic agents that could synergize the antitumor effects of cisplatin in basal-like breast cancers. Through the use of a small chemical library that targets some of the most relevant oncogenic pathways in basal-like breast cancer, we show that inhibition of mTOR by rapamycin incurred a specific synergistic effect with cisplatin in basal-like breast cancer cells. This synergistic effect is mediated in part through the induction and activation of p73 in the presence of rapamycin and cisplatin, respectively. Together, our findings demonstrate evidence of a synergistic relation between rapamycin and cisplatin in both inhibition of cell growth and induction of apoptosis. This suggests that rapamycin and cisplatin may be a rational combination of a targeted therapy for the refractory basal-like breast cancers. Materials and Methods Cell lines and cell culture The human breast carcinoma cell lines MCF-7, T47D, MDA-MB-231, MDA-MB-468 and HCC1937 were obtained from the American Type Culture Collection (Manassas, VA) and maintained in RPMI 1640 medium containing 10% fetal bovine serum (FBS), 100 IU/ml penicillin and 100 ÃŽÂ ¼g/ml streptomycin (Sigma-Aldrich, St. Louis, MO, USA) at 37 °C with 5% CO2. MTT cell proliferation assay Dose-response curves and IC50 values were determined using the methyl thiazolyl tetrazolium (MTT) cell viability assay as described previously [4, 13]. Cells were seeded into 96-well plates for 24 hours at a density of 5 ÃÆ'- 103 cells/well. Serial drug dilutions were prepared in medium immediately before each assay, and viable cell masses following 3 days of drug exposure were determined by cell-mediated MTT reduction. Cell growth as well as drug activity was determined by measuring absorbance at 550 nm using an Anthos systems plate reader. Construction of IC50 mean graph The IC50 mean graph was constructed as defined by the Developmental Therapeutics Program of the National Cancer Institute (http://dtp.nci.nih.gov). The mean graph consists of positive (more sensitive) and negative (less sensitive) delta values, generated from a set of IC50 values by using a three-step calculation. The IC50 values for each of cell line against the tested compound were converted to log(IC50) values. For each tested compound, the log(IC50) values are averaged. Finally, the individual IC50 value is then subtracted from the average to generate the delta value. Positive delta values project to the right of the vertical line and represent cellular sensitivities to the test agent that exceed the mean. Negative values project to the left and represent cell line sensitivities to the test agent that are less than the average value. Library screening The Inhibitor Select„ ¢ chemical library which consists of 160 well-characterized, cell-permeable inhibitors was purchased from EMD Chemicals, USA. MDA-MB-468 cells at the logarithmic phase of growth were seeded into 96-well plate at a density of 5 ÃÆ'- 103 cells/well. Each compound was added to a final concentration of 10  µM in the absence or presence of 1  µM cisplatin. Plates were incubated for 72h at 37 °C. Cell proliferation was examined using MTT assay as described previously. Combination treatments that induce growth inhibition higher than those of the same doses used alone (p Drug interaction analysis Drug combination analysis was performed by using the method as described by Chou and Talalay [14]. Briefly, cells were seeded at 5 ÃÆ'- 103 cells/well in 96-well plates and treated with various concentrations of cisplatin and compound alone or in combination for 72h. Cell proliferation was measured in each well by MTT assay. Multiple drug dose-effect calculations and the combination index plots were generated using Calcusyn software (Biosoft, Cambridge, UK). Combination index, CI 1 indicate synergism, additive effect and antagonism, respectively. Apoptosis assays Quantitation of apoptosis by annexin V/PI staining was performed as described previously [3, 4]. Briefly, both floating and attached cells were collected 72h after drug treatments. Apoptotic cell death was determined using the BD ApoAlert annexin V-FITC Apoptosis Kit (BD Biosciences, USA) according to the manufacturers instructions, and cells were analyzed on a FACSCalibur flow cytometer using CellQuest Pro software (version 5.1.1; BD Biosciences, USA). Quantitative PCR (qPCR) analysis Total RNA from cells was extracted using Qiagen RNA isolation kit (Qiagen, Valencia, CA, USA) according to the manufacturers protocol. First-strand cDNA was synthesized from total RNA using random hexamer primers and the SuperScript II system for RT-PCR (Invitrogen, Carlsbad, USA). Gene expression levels were measured by qPCR using the iQ SYBR Green Supermix reagent and an Biorad iQ5 real-time PCR detector system (Bio-Rad, Richmond, CA, USA). Data analysis was performed using Opticon Monitor Analysis Software V1.08. The expression of each gene was normalized to ÃŽÂ ²2M as a reference. The relative copy numbers were calculated from an 8-point standard curve generated from a 10-fold serial dilution of full-length cDNA constructs as described previously [3, 4]. Specific forward and reverse primer sequences are as follows : TAp73fwd, 5-GCACCACGTTTGAGCACCTCT-3; TAp73rev, 5- GCAGATTGAACTGGGCCATGA-3; ÃŽÂ ²2Mfwd, 5-AGCTGTGCTCGCGCTACTCTC-3; ÃŽÂ ²2Mrev, 5-CACACGGCAGGCATACTCATC-3; PUMA fwd PUMArev NOXAfwd NOXArev. The conditions for all QRT-PCR reactions were as follows: 3 minutes at 94 °C followed by 40 seconds at 94 °C, 40 seconds at 60 °C, and 25 seconds at 72 °C for 40 cycles. All PCR products were confirmed by the presence of a single peak upon melting curve analysis and by gel electrophoresis. No-template (water) reaction mixtures and no-RT mixtures were performed on all samples as negative controls. All experiments were performed in duplicate. Protein isolation and Western blot analysis Protein lysates from cells were extracted in ice-cold lysis buffer (0.75% NP-40, 1 mM DTT, and protease inhibitors in PBS). Total protein (25 ÃŽÂ ¼g) was subjected to SDS-PAGE followed by immunoblotting with the following antibodies: p73 (diluted 1:1,000, Ab-2; CalBiochem); pS6K (diluted 1:1,000; Cell Signaling Technology); S6K (diluted 1:1,000, Ab9645; Abcam); and ÃŽÂ ²-tubulin (diluted 1:2,500, D-10; Santa Cruz Biotechnology). Lentiviral production and infection The shRNA lentiviral constructs were created by transferring the U6 promoter-shRNA cassette into a lentiviral backbone, and high-titre lentiviral stocks were generated by co-transfection with packaging vectors into 293T cells as described previously [3, 4, 13]. The shRNA target sequences for TAp73 was 5-GGATTCCAGCATGGACGTCTT-3. The TAp73 targeted sequence is found within p73 exon 3. Therefore, this shRNA does not target ΆNp73 [4]. RESULTS Selective sensitivity of basal-like breast cancer toward cisplatin To gain an overview of the selectivity of chemotherapeutic agents for basal-like breast cancer cells, we compared their antiproliferative properties in a panel of basal-like and luminal-like breast cancer cell lines which has been validated previously through gene profiling [15]. All cells were treated with increasing concentrations of cisplatin, paclitaxel or doxorubicin for 72 hours and growth measured using the MTT assay. Figure 1A and B summarizes the results from these breast cancer cell lines in which basal-like breast cancer cells demonstrated selective sensitivity to cisplatin. This selectivity was absence in cells treated with paclitaxel or doxorubicin suggesting that basal-like breast cancer cells confer selective sensitivity towards cisplatin (Figure 1A, B and Supplement Table 1). Small chemical library screening identify rapamycin as synergistic agents for cisplatin Although cisplatin is currently one of the most used agents in the treatment of cancer, the use of cisplatin is hampered by its side effects, especially neurotoxicity, nephrotoxicity and rug resistance [16]. Hence, the present study was aimed to identify chemosensitizers that could synergize the effects of cisplatin for treatment of basal-like breast cancers. To identify small molecules that enhance sensitivity of basal-like breast cancer cells to cisplatin, a cell-based high-throughput screen was performed using MDA-MB-468 cell line and a small chemical library consisting of 160 well validated specific inhibitors. The screens were done in 96-well plates to which compounds were added at 10  µM, followed by cisplatin at 1  µM. Cell viability was measured 72 hours later by MTT assay. Each plate included controls of untreated cells, cells treated with compounds or cisplatin only, and cells treated with a combination of both agents. Combinations of the treatments that induced growth inhibition higher than those of the same doses used alone (p The molecules identified in this screen includes rapamycin, [3-(Pyridin-2-yl)-4-(4-quinonyl)]-1H-pyrazole (LY364947), 4-(3-Chloroanilino)-6,7-dimethoxyquinazoline (AG1478), (E)3-[(4-Methylphenyl)sulfonyl]-2-propenenitrile (BAY11-7082), 2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) and 4-(4-Fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580). Structures of these compounds and their growth inhibitory effects were shown in Figure 2. The molecular target of these compounds was listed in Table 1. The 6 compounds identified are specific inhibitors of the mTOR, TGF-à ¯Ã‚ Ã‚ ¢, EGFR, NFà ¯Ã‚ Ã‚ «B PI3K/AKT and MAPK pathways which have been previously reported to be upregulated specifically in basal-like breast cancers [7, 17-20]. However, when tested for synergism with cisplatin at fixed concentration ratio, only rapamycin showed synergism when combined with cisplatin in MDA-MB-468 cells using the isobologram method that simulate the median-dose combination index (CI) [14]. The mean combination index at ED50, ED75, and ED90 of rapamycin (10:1 cisplatin:rapamycin) when combined with cisplatin was 0.52 à ¯Ã¢â‚¬Å¡Ã‚ ± 0.06, where combination index Specific synergistic effects of rapamycin and cisplatin in basal-like breast cancer cells Next, we sought to investigate if combination of cisplatin with rapamycin exhibit specific synergism in basal-like breast cancers by comparing their effects in a panel of breast cancer cell lines. The antiproliferative effect of treatment was evaluated using MTT assays and drug interaction was assessed by the isobologram method as described in the previous section. The results demonstrated that combination of rapamysin and cisplatin exhibited selective synergistic effects only in the basal-like MDA-MB-468, MDA-MB-231 and HCC1937 cells, but not in the luminal-like T47D or MCF-7 cells (Figure 3A and Table 2). To ensure that the lack of synergistic effects of rapamycin and cisplatin observed in luminal-like cells is not due the general lack of sensitivity of luminal-like cells to cisplatin per se, we compared the apoptotic effects of cisplatin and rapamycin alone or in combination in MDA-MB-231 and T47D cells using an equal potent dose of cisplatin (IC50 dose). Both cell lines exhibited similar amount of apoptosis following treatment with their respective IC50 dose of cisplatin. Interestingly, when both cell lines were treated with combination of cisplatin and rapamycin, synergistic effects were evidenced only in MDA-MB-231 cells but not in T47D cells. The potentiation effects of rapamycin observed in MDA-MB-231 cells were further enhanced by sequential treatment with rapamycin for 6 hours followed by cisplatin (data not shown). These results demonstrated that rapamycin is capable of sensitizing basal-like breast cancer cells to cisplatin, suggesting that the synergistic effects of rapamyc in and cisplatin may be mediated through a common pathway. Rapamycin sensitizes basal-like cells to cisplatin through p73 up regulation Previous study has shown that inhibition of mTOR by rapamycin up regulate p73 in breast cancer cells [21]. We and others have also demonstrated that p73 is overexpressed in a subset of triple-negative breast tumors and that p73 is required for cisplatin sensitivity in basal-like breast cancer cells [4]. On the basis of these findings, we ask if the synergistic effects of rapamycin and cisplatin combination could be explained by the activation of the p73 pathway. To test this notion, MDA-MB-231 cells were treated with 10  µM of cisplatin and 100 nM rapamycin alone or in combination for 48 hours. mTOR inhibition was confirmed using phospho-S6K as a marker of mTOR activity. Quantitation of the mRNA and protein expression of the TAp73 was performed using qPCR and immunoblotting, respectively. The results showed that treatment of rapamycin or cisplatin alone did not change the expression of TAp73 mRNA but induced significant up regulation of TAp73 protein expression in MDA-MB-231 cells (Figure 4A and B). Next, we evaluated the expression of the two potent pro-apoptotic BH3 only proteins, PUMA and NOXA, which has been identified as specific p73 target genes, using qPCR [22, 23]. As expected, treatment of cells with cisplatin for 48 hours induced mRNA expression of PUMA and NOXA in both MDA-MB-231 and MDA-MB-468 cells. Significant induction of PUMA and NOXA were also observed in MDA-MB-231 cells but not in MDA-MB-468 cells following treatment with rapamycin alone. When cells were treated with combination of cisplatin and rapamycin, the expression of PUMA and NOXA was further enhanced, corroborated with the massive induction of apoptosis as shown in Figure 3B. Together, these results suggest that rapamycin synergize cisplatin activity in basal-like cells through induction of p73 pathway. p73 is required for the synergistic effects of rapamycin and cisplatin in basal-like breast cancer cells To further evaluate whether p73 is the effector of the synergistic effects of rapamycin and cisplatin in basal-like breast cancer cells, we generated a series of isogenic cell lines that have been depleted for TAp73 by stably expressing a shRNA species that target specifically human TAp73. Unlike MDA-MB-231 cells which express one predominant TAp73 isoform (TAp73à ¯Ã‚ Ã‚ ¢) isoform, MDA-MB-468 cells express high levels of two p73 isoforms, TAp73à ¯Ã‚ Ã‚ ¡ and TAp73à ¯Ã‚ Ã‚ ¢ [21]. Figure 5A showed efficient knock-down of TAp73 isoforms in MDA-MB-231 and MDA-MB-468 cells. As expected, treatment of cisplatin alone induced significant amount of apoptosis in MDA-MB-468 vector control cells. This apoptotic effects were further enhanced in the presence of rapamycin, consistent with our previous observations (Figure 3B). In stark contrast, depletion of TAp73 not only reduced the amount of apoptosis following treatment of cisplatin alone but also completely abrogated the synergistic effects of rapamycin (Figure). This result is further supported by the isobologram analysis which showed a lack of synergism of rapamycin-cisplatin treatment in the TAp73 depleted cells. Together, these results suggest that TAp73 is required for the synergistic effects of rapamycin and cisplatin in basal-like breast cancers. DISCUSSION By gene profiling, breast cancers can be classified into 5 molecularly distinct subtypes: luminal A, luminal B, HER2+, basal-like and normal breast cancers. The basal-like subtype, which represents 15-20% of breast cancers, has been subjected to extensive investigation in recent years due to its association with poor patient survival [1, 2, 20, 24]. Unlike many breast cancers, patients diagnosed with basal-like breast cancers are not eligible for molecular targeted therapy that target ER (e.g. tamoxifen, aromatase inhibitors) or HER2 (e.g. Herceptin) as they do not express the estrogen receptor (ER) or progesterone receptor (PR), nor do they have amplified HER2 [1, 24]. The treatment option therefore is relied on aggressive conventional chemotherapies which have limited efficacy, many side effects and often high rate of relapse. Hence, development of an effective therapeutic strategy remains an important goal in the management of basal-like breast cancer. Several lines of evidence has suggested a link between basal-like breast cancers and BRCA1 deficiency [7, 25, 26]. In most cases, the clinical features and outcomes for women with sporadic basal-like breast cancers are broadly similar to those with BRCA1-related cancers including high tendency of developing high grade, high mitotic index tumors, shorter time of relapse, similar pattern of metastatic spread and cytogenetic changes associated with frequent loss of X-chromosome inactivation [7, 27-32]. The majority of BRCA1-associated cancers are also triple-negative (ER, PR and HER2 negative), express basal cytokeratins and other markers commonly seen in basal-like breast cancers (e.g. p53, P-cadherin and EGFR) [7]. Gene expression profiling also demonstrated that BRCA1-associated cancers segregate strongly with basal-like breast cancers [2, 29, 33, 34]. Although BRCA1 somatic gene mutations are uncommon in sporadic basal-like cancers, these tumors have been shown to have a dysfunction al BRCA1 pathway due to BRCA1 gene promoter methylation and/or BRCA1 pathway transcriptional inactivation [7, 25, 26]. The fundamental biological similarities between hereditary BRCA1-related breast cancers and basal-like cancers suggest that strategies targeting the dysfunctional BRCA1 pathway may be effective in basal-like breast cancers. There is increasing evidence that the DNA repair defects characteristic of BRCA1 related cancers, especially defective homologous recombination, confer sensitivity to certain systemic agents, such as platinum-based chemotherapy and poly(ADP-ribose) polymerase (PARP) inhibitors [34-38]. Indeed, recent clinical studies revealed that sporadic basal-like cancers responded to platinum-based chemotherapy and were associated with a high rate of complete pathologic response [9, 11, 38]. Consistent with the clinical data, our in vitro study also reveals that basal-like breast cancer cells confer specific sensitivity to cisplatin as compared to other chemotherapeutic agents (e.g. doxorubicin or paclitaxel) (Figure 1), further support research into the utility of platinum-ba sed agents in basal-like breast cancers. Given the high specificity and response rate of basal-like breast cancers toward platinum-based therapy, our focus is to maximize the benefits associated with this therapy through drug combination strategies. Using a small chemical library consisted of 160 well-validated and specific inhibitors that target the human kinome, we have identified 6 compounds that significantly potentiate the antiproliferative effects of cisplatin in basal-like breast cancer cells. These compounds include rapamycin, LY364947, AG1478, BAY11-7082, LY294002 and SB203580 which targets the mTOR, TGFà ¯Ã‚ Ã‚ ¢RI, NFà ¯Ã‚ Ã‚ «B, PI3K/AKT and MAPK pathway respectively. Of note, these pathways have been reported previously to be over activated in basal-like breast cancers [7, 17, 18, 20]. To further investigate the mode of interaction between these compounds and cisplatin, we performed a drug combination study using the isobologram approach as described previously (Ref). Out of the 6 compounds identified, rapamycin showed the strongest synergistic effects with cisplatin while others (LY364947, AG 1478, BAY11-7082, LY294002 and SB203580) showed mainly additive effects. This result is consistent with other studies which show that inhibition of mTOR by RNAi or small molecules (e.g. rapamycin, CCI-779, RAD001) enhances cisplatin chemosensitivity in ovarian [39-41], endometrial [42], head and neck [43, 44], lung [45], skin [46, 47] and liver [48] cancers. We next compared the synergistic effects of rapamycin in combination with cisplatin in a panel of luminal-like and basal-like breast cancer cell lines that has been previously validated by gene profiling [15]. Intriguingly, the synergistic effects were observed only in MDA-MB-468, MDA-MB-231 and HCC1937 basal-like cells, but not in MCF-7 or T47D luminal-like cells. Several models have been proposed to explain the synergistic effects of rapamycin and cisplatin in cancer cells. Beuvnk et al., 2005 showed that RAD001 (Everolimus), a rapamycin derivative, dramatically enhances cisplatin-induced apoptosis in wild-type p53 but not mutant p53 tumor cells by inhibiting p53-induced p21 expression [49]. Wangpaichitr et al., 2008 demonstrated that inhibition of mTOR by CCI-779 decreased levels of the anti-apoptotic proteins, BCL2/BCLxL, and increasing apoptosis in lung cancer cells that is resistance to cisplatin [50]. Although these models provide important evidence for mTOR inhibition and cisplatin synergism in cancer cells, it fails to explain the specific synergism we observed in basal-like breast cancer cells, as the basal-like cells that we tested are p53 mutated and do not express high level of BCL2/BCLxL (data not shown). This led us to postulate that a common signal transduction pathway inhibited by rapamycin may be an important component that sy nergizes cisplatin sensitivity in basal-like cells. Since p73 has been reported to mediate cisplatin sensitivity in a subset of triple-negative breast cancer cells [4] and that inhibition of mTOR by rapamycin or RNAi lead to upregulation of p73 [21], we postulated that activation of the p73 pathways might be important for the synergistic effects of rapamycin. To test the role of p73 in rapamycin and cisplatin synergism, we first evaluated the expression of p73 mRNA and protein levels following treatment with cisplatin or rapamycin alone or in combination in MDA-MB-231 cells. Consistent with previous studies, treatment of cells with cisplatin or rapamycin alone induces p73 protein expression followed by transcriptional activation of the 2 potent pro-apoptotic p73 target genes, PUMA and NOXA. When MDA-MB-231 cells were co-treated with rapamycin and cisplatin, the elevation of p73 and its pro-apoptotic target genes were synergistically enhanced. The observed changes in p73 protein in MDA-MB-231 cells, however, were not due to parallel changes in p73 RNA levels, suggesting that inhibition of mTOR might lead to inactivation of a yet unknown p73 specific protein degradation pathway. To validate that the rapamycin and cisplatin synergism is mediated by p73, we generated isogenic MDA-MB-231 and MDA-MB-468 cells that were depleted for p73 using a lentiviral-shRNA that target specifically the transactivating isoform of p73 (TAp73). Indeed, depletion of TAp73 in MDA-MB-231 and MDA-MB-468 cells completely abrogated the synergistic effects of rapamycin suggesting that the synergism between rapamycin and cisplatin required p73 function. Although the combination of cisplatin and rapamycin has not been previously investigated in clinical study, it is worth noting that a phase II neo-adjuvant clinical trial of cisplatin and RAD001 (Everolimus), in patients with triple-negative breast cancers has recently open for recruitment (ClinicalTrials.gov Identifier: NCT00930930), and will be able to address the potential of cisplatin and mTOR inhibitors combination therapy directly. It would be equally intriguing to determine the role of p73 related pathway as potential biomarkers that might predict response to treatment given the pivotal role of p73 in the synergistic effects of mTOR inhibition and cisplatin sensitivity. In conclusion, combination of mTOR inhibitors and cisplatin may be a useful therapeutic strategy in basal-like breast cancers.

Effect of Concentration on Osmosis Essay -- GCSE Biology Osmosis Cours

Effect of Concentration on Osmosis Aim To find out how the concentration of sucrose solution affects the mass of the potato chip left in the solution for one day. Prediction I predict that when the sucrose concentration is low the potato chip will gain mass. This is because there will be a higher sucrose concentration in the potato chip so water will go into the potato from the solution. I predict that when there is a high concentration of sucrose the potato will lose mass. This is because there is a higher concentration of sucrose solution in the solution compared to that in the potato chip so water from the potato will go into the solution to even it out. Osmosis is "the movement of a solvent through a selectively permeable membrane (as of a living cell) into a solution of higher solute concentration that tends to equalize the concentrations of solute on the two sides of the membrane" Osmosis is the movement of water from high water concentration to lower water concentration through a selectively permeable membrane. Selectively permeable membranesare very thin layers of material (cell membranes are selectively-permeable), which allow some molecules to pass through them but prevent other molecules from passing through. Cell membranes will allow small molecules like Oxygen, water, Carbon Dioxide, Ammonia, Glucose, amino-acids, etc. to pass through. Cell membranes will not allow larger molecules like Sucrose, Starch, protein, etc. to pass through. In my experiment I will have a test tube with a potato chip in. The outside wall of the potato chip is selectively permeable so it lets water pass through it but not bigger molecules such as sucrose. In the test tubes I will put different concentrations of sucrose solution. When the concentration of the solution is lower than that in the potato, water will pass through the selectively permeable wall into the potato. Potato cells Sucrose solution The mass of the potato chip increases Sucrose molecule Water molecule When the sucrose solution is stronger outside if the potato chip water will move out from the potato chip into the solution. When the concentration is the same on both sides of the selectively permeable wall nothing passes through it and the mass will stay the same. Plan Apparatus Five test tubes Labels Ruler Scales Tissue... ...hips in each test tube. This would make it more accurate as when I had two in a test tube if one of them was a long way out it made the graph not follow the line well when I plotted the averages. There was one anomalous result at 0.5 mol. I think this was because we patted them dry when we got them out of the test tubes as we did not want to weigh there water on the outside of the potato but I think that we may not have dried them all equally so this anomalous result may have been due to it having water left on the outside of it. Also the potato itself was not from the same part of the potato and was not exactly the same size, although I did try to cut them to 36mm each. I could also try the same experiment but with different volumes of cell tissues and see if the percentage change differed with a bigger and smaller surface area. I could now investigate the smaller range near to 0.25 to see the sucrose concentration equivalent to the potato. Finally, I could extend the experiment to a more exact level by looking at the potato cylinders under a microscope, then I would be able to see the cells in greater detail and draw some more observational results.

Biblical Allusions Throughout of Mice and Men Essay

â€Å"He calls Of Mice and Men a parable that illustrates the biblical conflict between the brothers Cain and Abel† (Goldhurst 48). Therefore the people who have read the story Of Mice and Men can automatically see the resemblance between the two stories. Of Mice and Men is a novelette by John Steinbeck, it is about two men who are migratory workers that works on farms. Of Mice and Men contains many Biblical allusions including the Story of Cain and Abel, the longing for Eden, and facing temptation. In Of Mice and Men and the Old Testament the themes are similar. It is stated in the â€Å"A Parable Curse of Cain.† â€Å"Of Mice and Men is a story about the nature of man’s fate in a fallen world, with particular emphasis upon the question: is man destined to live alone, a solitary wanderer on the face of the earth, or is it the fate of man to care for man, to go his way in companionship with another? This is the same theme that occurs in The Old Testament† (Goldhurst 49). This proves that Of Mice and Men and The Old Testament have a similar theme. One reoccurring theme in Of Mice and Men and The Old Testament is loneliness will always follow man and innocence keeps ideas alive. The curse that the Lord placed upon Cain was that agricultural labor was going to be difficult, and he will be lonely while being a fugitive (Genesis 4:12). In Of Mice and Men George and Lennie are fugitives that are migratory workers but George at times feels lonely even though he has Lennie because he doesn’t have a romantic partner. This shows how these two stories are similar within their themes. Worked Cited Goldhurst, William. â€Å"A Parable of the Curse of Cain.† Readings on John Steinbeck- Of Mice and Men. Ed. Jill Karson, Bruno Leone, Brenda Salcup, and Brenda Szumski. San Diego, CA: Greenhaven Press, 1998. 48-58. Print The New Oxford Annotated Bible. Ed. Bruce M. Metzger, Roland E. Murphy, and Bernhard W. Anderson. New York: Oxford University Press, 1994. 2-7. Print. Owens, Luis. â€Å"Of Mice and Men: The Dream of Commitment.† Modern Critical View John Steinbeck. Ed. Harold Bloom. New York: Chelsea House, 1987. 145-149. Print.

Percent Composition by Mass Example Problem

Percent composition by mass is a statement of the percent mass of each element in a chemical compound or the percent mass of components of a solution or alloy. This worked example chemistry problem works through the steps to calculate percent composition by mass. The example is for a sugar cube dissolved in a cup of water. Percent Composition by Mass Question A 4 g sugar cube (Sucrose: C12H22O11) is dissolved in a 350 ml teacup of 80 Â °C water. What is the percent composition by mass of the sugar solution? Given: Density of water at 80 Â °C 0.975 g/ml Percent Composition Definition Percent Composition by Mass is the mass of the solute divided by the mass of the solution (mass of the solute plus mass of the solvent), multiplied by 100. How to Solve the Problem Step 1 - Determine mass of solute We were given the mass of the solute in the problem. The solute is the sugar cube. masssolute 4 g of C12H22O11 Step 2 - Determine mass of solvent The solvent is the 80 Â °C water. Use the density of the water to find the mass. density mass/volume mass density x volume mass 0.975 g/ml x 350 ml masssolvent 341.25 g Step 3 - Determine the total mass of the solution msolution msolute msolvent msolution 4 g 341.25 g msolution 345.25 g Step 4 - Determine percent composition by mass of the sugar solution. percent composition (msolute / msolution) x 100 percent composition ( 4 g / 345.25 g) x 100 percent composition ( 0.0116) x 100 percent composition 1.16% Answer: The percent composition by mass of the sugar solution is 1.16% Tips for Success Its important to remember you use the total mass of the solution and not just the mass of the solvent. For dilute solutions, this doesnt make a huge difference, but for concentrated solutions, youll get a wrong answer.If youre given the mass of solute and mass of solvent, life is easy, but if youre working with volumes, youll need to use density to find the mass. Remember density varies according to temperature. Its unlikely youll find a density value corresponding to your exact temperature, so expect this calculation to introduce a small amount of error into your calculation.