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Essay about RJ and Ge Compare and Contrast - 1320 Words

Dai 1 Kevin Dai Word Count: 1146 Compare and Contrast (Romeo and Pip) Love is a topic that innumerable authors delight in writing about. In each of their masterpieces, love is a driving force in he or she’s makeup. The main characters of Shakespeare’s Romeo and Juliet and Dicken’s Great Expectations, Romeo and Pip, are no exception. Although Romeo and Pip live in very different environments, love affects their maturity, loyalty, and fluctuating mood. Love drastically changes both Pip and Romeo’s maturity throughout both works. In the beginning of the play, Romeo sorrowfully conveys that Rosaline â€Å"[lives uncharmed] [f]rom Love’s weak childish bow†¦Ã¢â‚¬ (Kinsella 777). Romeo, starting off deep in ecstacy, describes love as a â€Å"weak childish bow†Ã¢â‚¬ ¦show more content†¦Pip maturely releases his irrational desires for Estella’s love and forgives her for any personal injuries done to him. Pip’s long journey fo r Estella’s love transformed him from a superficial dreamer to a mature gentleman. Though both initially romantic idealists, Romeo and Pip both become more realistic and learn to cope with the harsh aspects of love. The power of love also impacts the loyalty of both characters. At the Capulet’s party, the enlightened Romeo looks at Juliet and claims that â€Å"[he] ne’er saw true beauty till this night† (Kinsella 788). Before the party, Romeo was infatuated with Rosaline (saying that he â€Å"[n]e’er saw her match since first the world begun†), but when he notices Juliet, newfound love drives away and replaces his previous loyalty (Kinsella 780). On the day of Pip’s pursuit of expectations, he assures Joe â€Å"that [he] shall never forget [him]† (Dickens 115). Pip’s need to reassure Joe discloses that he has a premonition that his loyalty will be shaken. His love for Estella is pulling him away from the person who ought to have Pip’s complete loyalty. After Mercutio’s death at the hand of Tybalt, Dai 3 Romeo, utters that Juliet’s â€Å"beauty hath made [him] effeminate / [a]nd in [his] temper soft’ned valor’s steel† (Kinsella 822). Romeo believes that love for Juliet has dragged him too far from his loyalty to Mercutio, whom Romeo thinks is just as important. When Joe mentions Estella’sShow MoreRelatedCompare Leadership Styles Between Jack Welch and Jeff Immelt4058 Words   |  17 PagesTitle: Compare and Contrast Two Leaders Executive Summary This paper would take leadership into account by comparing and contrasting two well-known leaders in General Electric (GE). The paper first introduces two leaders with some brief biographies, characteristics and their contribution to the GE. It then looks at who would be the more effective leader by providing with some aspects of leadership. It then comes up with some skills these people employed in their leadership to help GE growth rapidlyRead MoreCorporate Entrepreneurship at Ge and Intel2827 Words   |  12 Pages2010 EABR ETLC Conference Proceedings Dublin, Ireland Corporate Entrepreneurship at GE and Intel John Zimmerman, Zayed University, U.A.E Abstract This is the first of three planned articles concerning Corporate Entrepreneurship (CE). The author is a former entrepreneur practitioner who secured an earned doctorate from Pepperdine University in 2008, and who now teaches at Zayed University in the United Arab Emirates. 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In fact it was found that models, at least in Italy, are rarely compared and if they are, it is on a one-to-one basis. The intent is to at least start to bridge and compare models and show how new models can be realised. The paper closes with the proposal of a new model, the Ward-Rivani model, which does not claim to be the most universal rather a complementary and perhaps useful platform for future work on strategyRead MoreGe Honeywell23318 Words   |  94 Pagestransatlantic conflict March 2005 Jeremy Grant (Graduate Institute of International Studies, Geneva) and Professor Damien J. Neven (Graduate Institute of International Studies, Geneva) Financial support from the TMR program on  « Competition Policy in international markets  » is gratefully acknowledged. The authors would also like to thank all those participants in GE/Honeywell who generously gave of their time to discuss the case. (Acknowledgements to be approved). Thanks are also due to SarahRead MoreTraditional and Contemporary Issues and Challenges14128 Words   |  57 Pagesrecent years, in part because its top managers have focused too much attention on quantitative methods and not enough attention on the strategic and behavioral elements of their business. Specially prepared for d03371341 on 21 Apr, 2010 30 P A R T O N E †¢ An Introduction to Management Pepsi regrouped and emerged as a strong competitor. Pepsi’s stock price has climbed by one-third since 2001, while Coke’s dropped by one-third, showing the different investor perceptions of the two rivals. HowRead MoreEffects Of Devaluation Of Rmb On China Essay2127 Words   |  9 PagesEffects of devaluation of RMB on China Qiluo Zhang, Lucy, 988139 GE 2021 W02, Dr. Richard J. Braxton November, 12, 2016 Introduction The Chinese Central Bank devalued the RMB on August 11, 2014 which was the largest drop in the RMB ever. And the devaluation continued for two days and accumulatively knock 4.4% off the value of RMB on August 13, 2015(COUGH BRADSHER). While Chine grew to become the second largest economy in the world, RMB, as the national currency of China has been gainingRead MoreStrategic Management20602 Words   |  83 Pagesordered in 2007 until the 2012–2013 range. Sources: J. Bruner G. Maidment, 2007 Breaking up Airbus, Forbes, http://www.forbes.com, March 20; N. Clark , L. Wayne, 2007 Airbus hopes its planes, not its setbacks, will stand out, New York Times, http://www.nytimes. , com, June 18; G. Colvin, 2007 Boeing prepares for takeoff, Fortune, June 11, 133; C. Matlac S. Holmes, 2007 , , Airbus revs up the engines, BusinessWeek, March 5, 41; D. Michaels, J. L. Lunsford, M. Trottman, 2007 Airbus , seals US

Free Interpretive Differences of Hawthorne Essay Example For Students

Free: Interpretive Differences of Hawthorne Essay s Young Goodman Brown Young Goodman Brown essays Young Goodman Brown Interpretive Differences Young Goodman Brown, universally acclaimed as one of Hawthornes best short stories, presents the student searching out its meaning with not only several possibilities but several rather ambiguous ones. D. M. McKeithan, in an article entitled Young Goodman Brown: An Interpretation (Modern Language Notes, 67 1952, 93), has listed the suggestions that have been advanced as the theme of the story: the reality of sin, the pervasiveness of evil, the secret sin and hypocrisy of all persons, the hypocrisy of Puritanism, the results of doubt or disbelief, the devastating effects of moral scepticism . . . the demoralizing effects of the discovery that all men are sinners and hypocrites. Admittedly, these themes are not as diverse as they might at first appear. They are, with the possible exception of the one specifically mentioning Puritanism, quite closely related. But meaning is not restricted to theme, and there are other ambivalences in the story that make its meanings both rich and elusive. After taking into account some matters of text and genre, we shall look at Young Goodman Brown from our traditional approaches. Textually, Young Goodman Brown, first published in 1835 in the New England Magazine, presents relatively few problems. Obsolete words in the story like wotst (know), Goody (Goodwife, or Mrs.), Goodman (Mr.) are defined in most desk dictionaries, and none of the other words has undergone radical semantic change. Nevertheless, as we have seen, although a literary work may have been written in a day when printing had reached a high degree of accuracy, a perfect text is by no means a foregone conclusion. With Hawthorne, as with other authors, scholars are constantly working on more accurate texts. For example, the first edition of this handbook used a version of Young Goodman Brown that contained at least two substantive variants. About three-fourths of the way through the story the phrase unconcerted wilderness appeared. David Levin, in an article entitled Shadows of Doubt: Specter Evidence in Hawthornes Young Goodman Brown' (American Literature, 34 November 1962, 346, n.8) points out that nineteen years after Hawthornes death, an edition of the story by George P. Lathrop printed unconverted for the first time: Every version before that, including Hawthornes last revision, had had unconverted. In that same paragraph the first edition of this handbook printed figure as opposed to apparition, the word that Levin tells us, occurred in the first published versions of the story. Obviously, significant interpretive differences could hinge on which words are employed in these contexts. .

When I was in the military the... free essay sample

When I was in the military they gave me a medal for killing two men and a discharge for loving one. ~Epitaph of Leonard P. Matlovich, 1988 (Thanks, Marlene)The famous irony that speaks volumes about Indias attitude towards the word or the very activity of sex is that, India being the sub-continent where the ancient Indian text Kamasutra was written by Vatsyayana in which an entire chapter is dedicated to erotic homosexual behaviour and activity- which, again went on to prove that homosexuality was prevalent in ancient India as made evident by the carved images on the Sun Temple in Odisha and the Khajurao temple in Madhya Pradesh . Kamasutra was the first sex treatise written in the world somewhere between 4th and 2nd century B.C and for a country that had a very liberal outlook and approach towards sex and homosexuality till 18th century B.C , it is comic , perturbing and queer that there should be a drastic change in peoples outlook towards these- now tabooed-subjects. We will write a custom essay sample on When I was in the military the or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page The country that was unprejudiced in its mind set is now nurturing anti-sex , homophobic bigots.What changed after 18th century? Why did people start despising homosexuals and consider them social deviants? Awadh (modern-day Lucknow), had a ruler who would practice living as the opposite gender at times, including changing sexual partners. Bengali novels from the late 19th century such as Indira describe lesbian relationships. And Sufi Muslim texts in East India explicitly mention homosexual male romance. But all of this was in the pre-18th century period. It seems that with progress of time , the mentality of the Indian society seems to have regressed. If such know acts of homosexuality, transsexuality and bisexuality were not unknown and condemned, then in 20th and 21st century , what made people denounce it ? It is said that homophobia is a legacy of the 157 year old colonial rule in India. In 1857 , with the Sepoy Mutiny that shook Britishers and Indians, because for the first time, India had aroused after the repeated acts of transgression on part of Britishers against the Indians. It gave a befitting reply to the Britishers and though it failed to claim its freedom, Britishers realised that India must be suppressed even harder than before One of the main driving forces of British imperialism was its ideology of being a civilising mission. Drawing on the rhetoric of early settlers, colonialists plan ned on using Britains territorial superiority to impose British values on the colonies. Part of this ideological thrust of Empire and civilisation euphuism was affiliated to even reforming the ways in which desire and love were accepted and practised and manifested itself in the moral policing of desire. And so, under the garb of civilisation British started propagating Christianity in India in order to civilise Indians. India was home to several religions except Anglican Christianity and after the Sepoy Mutiny in 1857, there was great opportunity to incorporate religious ardour into the legal system. As a country where gender and sexuality has been loosely conceptualised in the past, Indias custom and traditions were unacceptable to the Britishers and it was a conflict against the British Crowns idea of how a society should be. Victorian Christianity dictates that lying with another man as one lies with a woman is detestable and such homosexual offenders cannot enter the kingdom of heaven (Old Testament) . The question that arises here is : why is sex that is not per formed by a man and woman only ,detested? If homosexuals, transgender and transsexual do not cause any harm to the society , why are they looked down upon? The answer was this- that any sexual activity that doesnt lead to procreation is not an acceptable , is considered immoral and sinful. Any form of intimacy that didnt result in reproduction and gearing of children was unthinkable , primarily because sexual intercourse was seen only as an affair meant to keep the human race alive and not for self- gratification and hence, homosexuality was seen as the worst of these offences. With such inflexible vision in mind, the British Raj implemented Section 377 in the Indian Penal Code,1860. The Section 377 states, Unnatural offences: Whoever voluntarily has carnal intercourse against the order of nature with any man, woman or animal shall be punished with imprisonment for life, or with imprisonment of either description for a term which may extend to ten years, and shall also be liable to fine.Explanation: Penetration is sufficient to constitute the carnal intercourse necessary to the offence described in this section.Any person engaging in unacceptable carnal desire was to be jailed or fined or both and this law was transmitted to other British colonial outposts. Hence, by the use of legislation, Christian values were set to be imposed, acceptable and legal acts of intimacy were defined to create a utopian world for the Indians and redeem them from the uncivilised world they were living in.Subsequently, as it could have been anticipated, criminalising ones se xual orientation or preference had a devasting effect on the society, especially the hijra community in India. Earlier when there was a gender fluidity due to the presence of these hijra community, emphasise was laid more on respecting ones identity, way of expression and marriage relationship. However with the installation and implementation of the Section 377,people with sexual preferences or orientation that were unconventional were christened as the undesirable others. Due to the absence of pro-queer narrative , homophobia carved a niche for itself in the Indian society due to its legal backing and thus, the transgenders, homosexuals and hijras began to face abysmal discrimination. The irony that remains is that Britain itself decriminalized homosexuality and repealed the very laws it brought into India through the Sexual Offences Act of 1967 which decriminalizes homosexuality in private between consenting male adults over 21 years while India still remained in the dark cave carved in the colonial era. And because there is no central Hindu authority to regulate the stances of Hinduism on homosexuality, homophobics have ignored the past and in the name of religion, started propagating homophobia among the masses more. Strangely, when the Rigveda says regarding Samsa ra that Vikruti Evam Prakriti (perversity/diversity is what nature is all about, or, what seems un-natural is also natural), Indian society should consider people like us but with a different sexual preference , unnatural. The Lesbian,Gay,Bisexual,Trangender movement in India began with a study done by the math wizard Ms. Shakuntala Devi who interviewed homosexual men and published The World of Homosexual Men, where she bought out the plight of these men against the backdrop of the Emergency years and called for the need to sensitise the world about them. Since 1980s the Hijra community started forming conferences while in 1986, the first coming out story was published when the journalist Ashok Row Kavi penned his own story in a magazine and later went on to publish the first magazine for queer men called Bombay Dost and open the Humsafar Trust that advocated awareness about HIV/AIDS and LGBTQ. Also in 1987, two police women went on to marry each other , such marriage being the first documented of its kind, although later both were discharged from their respective duty which goes on to show the toxic level of intolerance of the Indian society and the government towards the homosexuals. The 90s also saw the emergence of the lesbian movement in India. This was when activist and academic Gita Thadani set up Sakhi, a womens helpline and lesbian resource centre which facilitated cross-country networking between queer women.The medium of art was utilised to generate consciousness amongst the multitude with the production of BOMGay- the fir st film in India revolving around homosexuals and the actor R. Raj Rao, later went on to write the first gay romance novel – The Boyfriend in 2003; Sakhiyani, a book which talks about lesbian desire in ancient and modern India; Deepa Mehtas Fire- a movie based on lesbian relationship. Facing the Mirror: Lesbian Writing from India published in 1999 became an important bit of literature that increased visibility for queer women in the country and in the same year , an organisation called CALERI published the Lesbian Manifesto which pretty much broke the silence about lesbian women. In the recent times, films like Aligarh(2010), Sisak(2017) and Ka Bodyscapes( 2017), all which deal with homosexuality and the ideal concepts of masculinity. Magazines like Queer Ink magazine and India today have written exhaustively on the issues f homosexuality, LGBTQ movement and human right violations committed against the queers. At the age of 21, RJ Shilok is the only trans Radio Jockey in India to use the platform to engender awareness about LGBTQ issues, rascism etc. in 2016As for the idea that trans-people cant be parents, in 2001, Mumbai-based trans activist Gauri Sawant by adopting Gayatri, the orphaned daughter of a sex worker showed the world that they can be parents as well as anyone. Even in the political and educational field, transsexuals werent any less when in 2002, Kali became the first hijra person to stand for elections in Bihar. She was elected as ward councillor to the Patna Municipal Corporation. Again Manabi Bandhopadhyay became the first openly trans colle ge principal of Krishnanagar Girls College in 2015 and in the same year, Madhu Bai Kinnar was elected as the first trans Mayor in Raigarh. Sangini and Humraz were two separate helplines and support networks that were set up in 1997 for lesbians, transgender women and for gays and transgender men, respectively. Trans people and homosexuals were denied accommodation by prejudiced landlords which is why between 1998 and 1999, G.H.A.R (Gay Housing Assistance Resource) was founded to find safe living spaces for LGBTQ Indians who then didnt have to worry of being abused or of being constantly discriminated by the landlords or other tenants. There were multi-organisations like Voices against 377 which started sensitising people on issues like sexuality and mental health, human rights violations, sex reassignment and more. In recent times, parents have been encouraged to support and become campaigners of the LGBTQ youths when the Humsafar Trust in partnership with the online platform LoveMatters, floated the Strengthening Bridges which explored the relation between family ties and the development of LGBTQ individuals and appris ed parents the same. Even recently, parents have been invigorated to take up the rainbow flag which represents the LGBTQ community, forming first of its kind support group.LGBTQ activism was on full swing and by 2004 , the LGBTQ community was increasingly organised and was taking their fight for their rights on the streets and progressively becoming vocal about it. Society was endorsing the LGBTQ awareness through various means such as in 1999, a discotheque in Delhi hosted the first Gay Night giving the members of the LGBTQ community a private space to let their hair loose minus the fear of being abused and judged while the launch of Amour -a queer dating app launched in 2016 which was created with the promise of personalising its matchmaking service to suit the personal needs of individual users. In 2016 and 2017, the Chez – Q Jerome cafà © in Delhi and Amra Odhbhuta cafà © in Kolkata was opened, respectively in order to encourage celebration of identities. From 2014, Delhi University starte d giving out forms with the option of Third Gender category to improve access to education for trans students while Kerala-based Trans activist Vijayaraja Mallika set up Indias first ever school for transgender people called the Sahaj International in 2016. In order to encourage employment among trans people other than begging and being forced into the world of prostitution, trans activist and Mitr Trust founder Rudrani Chettri opened the first Trans Modelling agency in India to encourage the world to modulate the way they apperceive the idea of beauty, the fact that it goes beyond and deeper than just ones physical appearance or gender and then Kochi metro in 2017 employed 23 trans women mostly as ticket officers.When you hear of Gay Pride, remember, it was not born out of a need to celebrate being gay. It evolved out of our need as human beings to break free of oppression and to exist without being criminalized, pathologized or persecuted. Celebrate with us. ? Anthony Venn-Brown, A Life of Unlearning a journey to find the truthThe most powerful way of expressing our dissent , frustration and our concern for the societys need of understanding, is to take to the streets, come out and let it out loud! Peaceful protest accompanied by efficacious and persuasive rally crying and bywords caught the attention of the millennials who finally wanted to come out of the closet. In 1999, Calcutta held the first ever Gay Pride Parade in India with only 15 people marching but with an effectual message they were proud to be queers. Almost a decade later, New Delhi and Mumbai held their first Pride marches in 2008 and saw a promising turnout. The next year itself Chennai too held its first Rainbow Pride Walk with large number of various LGBTQ groups in attendance. More recently , Guwahati held its first pride Walk in 2013 where the LGBTQ community made their presence felt in the north east. Gurgaon Pride March was held in 2016 which brought into limelight Queer politics and visibility while Lucknow and Bhopal held their first ever Pride Marchs in 2017 which saw in attendance renowned trans activists around the country.

Russia history essays

Russia history essays In reading Peter McPhee's book The French Revolution 1789 - 1799 he makes the argument that as he put it ...creating the environment within which capitalist industry and agriculture would thrive.1 There are two ways in which the revolution created this environment, first by maximizing the capital in which the merchants, manufacturers and farmers would have to spend to fuel this new economy. The way in which the facilitated this was to abolish the tithe, feudal dues, and tolls on internal trade, and to set up a laissez-faire and laissez-passer economy. The second way is by making resources cheap and available to all. In an agrarian society like France was in the years of the revolution the only resource you need is land, and this was made available trough the taking and selling of church lands, and through the clearing of forest and expansion into the wastelands. All of theses helped created the institutional foundations on which capitalism could thrive.2 Furthermore, help j ump-start the industrial revolution, which had already started in the north of England and was soon to start in the United States. France during the 1780's was a seigneurialism economy in which the king and the nobles acquired their wealth. Placing a burden of the taxation firmly on the shoulders of the peasantry and the rising bourgeois. Many cities were ringed by wall not for protection, but to limit the access to the city so a toll could be collected on goods entering the city.3 This was not only just a hindrance to the movement of goods. The toll made almost did not promote a laissez-passer and national market. Besides this inconvenient of the toll system in the large cities of France the rural peasantry have tithe placed on their crops. In the countryside the church draw its vast wealth from the rural peasantry, which worked the land, upon which the Catholic Churched owned. The Church owned up to ten per cent of t...

How To Use Exclamations and Exclamation Marks in Spanish

How To Use Exclamations and Exclamation Marks in Spanish As in English, an exclamation or exclamatory sentence in Spanish is a forceful utterance that can range from a single word to almost any sentence that is given extra emphasis, either by using a loud or urgent voice, or in writing by adding exclamation points. Types of Exclamations in Spanish However, in Spanish, it is very common for exclamations to take particular forms, the most common of which is starting with the exclamatory adjective or adverb quà ©. (Quà © also functions elsewhere as other parts of speech, most often as a pronoun.) When used that way, quà © can be followed by a noun, adjective, an adjective followed by a noun, or an adverb followed by a verb. When it is followed by a noun, an article is not used before the noun. Some examples:  ¡Quà © lstima! (What a shame!) ¡Quà © problema! (What a problem!) ¡Quà © vista! (What a view!) ¡Quà © bonita! (How cute!) ¡Quà © difà ­cil! (How difficult!) ¡Quà © aburrido! (How tedious!) ¡Quà © fuerte hombre! (What a strong man!) ¡Quà © feo perro! (What an ugly dog!) ¡Quà © lejos est la escuela! (The school is so far away!) ¡Quà © maravillosamente toca la guitarra! (How beautifully she plays the guitar!) ¡Quà © rpido pasa el tiempo! (How time flies!) If you follow the noun after quà © with an adjective, ms or tan is added between the two words:  ¡Quà © vida ms triste! (What a sad life!) ¡Quà © aire ms puro! (What clean air!) ¡Quà © idea tan importante! (What an important idea!) ¡Quà © persona tan feliz! (What a happy person!) Note that the ms or tan doesnt have to be translated directly. When emphasizing quantity or extent, it also is common to begin an exclamation with cunto or one of its variations for number or gender:  ¡Cuntas araà ±as! (What a lot of spiders!) ¡Cunto pelo tienes! (What a head of hair you have!) ¡Cunta mantequilla! (What a lot of butter!) ¡Cunto hambre hay en esta ciudad! (What a lot of hunger there is in this city!) ¡Cunto he estudiado! (I studied a lot!) ¡Cunto te quiero mucho! (I love you a lot!) Finally, exclamations arent limited to the above forms; it isnt even necessary to have a complete sentence.  ¡No puedo creerlo! (I cant believe it!) ¡No! (No!) ¡Policà ­a! (Police!) ¡Es imposible! (Its impossible!) ¡Ay! (Ouch!) ¡Es mà ­o! (Its mine!) ¡Ayuda! (Help!) ¡Eres loca! (Youre crazy!) Using Exclamation Points Although this rule is commonly violated in informal Spanish, especially in social media, Spanish exclamation marks always come in pairs, an inverted or upside-down exclamation point to open the exclamation and a standard exclamation point to end it. The use of such paired exclamation marks is straightforward when an exclamation stands alone, as in all the examples above, but it gets more complicated when only part of a sentence is exclamatory. The upside-down exclamation mark doesnt exist in languages other than Spanish and Galician, a minority language of Spain. When an exclamation is introduced by other words, the exclamation points surround only the exclamation, which isnt capitalized. Roberto,  ¡me encanta el pelo! (Roberto, I love your hair!)i gano el premio,  ¡yupi! (If I win the prize, yippee!) But when other words follow the exclamation, they are included inside the exclamation marks.  ¡Me encanto el pelo, Roberto! (I love your hair, Roberto.)Yupi si gano el premio! (Yippee if I win the prize!) If you have several short connected exclamations in a row, they can be treated as separate sentences or they can be separated with commas or semicolons. If theyre separated by commas or semicolons, the exclamations after the first arent capitalized.  ¡Hemos ganado!,  ¡guau!,  ¡me sorprende!(We won! Wow! Im surprised!) Special Uses of Exclamation Marks To indicate strong emphasis, you can use up to three consecutive exclamation points. The number of marks before and after the exclamation should match. Although such use of multiple exclamation points isnt used in standard English, it is acceptable in Spanish.  ¡Ã‚ ¡Ã‚ ¡No lo quiero!!! (I dont want it!) ¡Ã‚ ¡Quà © asco!! (Thats disgusting!) As in informal English, a single exclamation mark can be placed within parentheses to indicate that something is surprising. Mi tà ­o tiene 43 (!) coches. (My uncle has 43 (!) cars.)La doctora se durmià ³ (!) durante la operacià ³n. (The doctor fell asleep (!) during the operation.) An exclamation mark can be combined with a question mark when a sentence expresses incredulity or otherwise combines elements of emphasis and questioning. The order doesnt matter, although the sentence should begin and end with the same type of mark.  ¡Ã‚ ¿Pedro dijo quà ©?! (Pedro said what?) ¿!Viste Catarina en la jaula!? (You saw Catarina in jail?) Key Takeaways As in English, exclamations in Spanish are sentences, phrases, or even single words that are especially forceful.It is common for Spanish exclamation to begin with quà © or a form of cunto.Spanish exclamations begin with an inverted exclamation mark.

LEGAL ENVIRONMENT PAPER Essay Example | Topics and Well Written Essays - 3000 words

LEGAL ENVIRONMENT PAPER - Essay Example For example, paying a government functionary in the home country a tip in order to facilitate licensing can be interpreted as bribery and subject to legal consequences or sanctions. In some foreign countries such payments are standard procedures of facilitating and expediting work, and failure to conform to such practices can often produce costly delays and probably significant losses. When there is a conflict between practices abroad and ethical and legal norms in the home country, the question that can arise is whether one should impose one’s ethical standard and values in a foreign country. Shouldn’t firms acknowledge ethical deviations for the sake of cultural sensitivity so as to avoid offending the officials and residents of the host country in the course of conducting its business? But first before going further let us attempt to define some terms and perhaps illustrate some basic concepts. The situation described above gives rise to some questions about corruption and bribery. Corruption, as defined by Joseph Nye more than 30 years ago, refers to the misuse of authority or a position of authority for some self-interested purpose (Nichols, P.M. (1997). And self-interest is not limited to pecuniary gain but may also include enhanced status, benefits to family and social circle, or any other perceived benefit. A bribe is a transaction which occurs when a good or service is transferred â€Å"across a technologically separable boundary.† (ibid). In bribery, the parties exchange benefits in an extra-legal setting, and, in most cases, the benefits conferred by the bribe giver is a quid pro quo for the benefit expected by the bribe giver.. The benefit may be anything of value to the bribe taker, made in the expectation of preferential treatment. From the economic and utilitarian perspective, bribery is objectionable because it distorts markets and

Marginal Analysis and how it is used in the world of economics Essay

Marginal Analysis and how it is used in the world of economics - Essay Example Perhaps, it is the most important concept in the analysis of economic activities. The marginal analysis theory states that individual should make a decision based on the incremental gains and losses that emerge from that decision. In a simplistic term, the marginal analysis balances the additional costs and benefits, derived out from taking a decision. Be it a student deciding whether to revise the chapters once more, or a producer whether to expand or stop production, optimal choice requires that costs and rewards should be equilibrated on the margin. Till the time additional benefit exceeds additional cost, the individual or the firm has to continue taking action so as to ensure that all excess benefits are accrued and vice versa. (Washington State University, N.D.). Marginal analysis is the study of the costs and benefits of the next unit of a good or a factor of production. The aim of the individual or a firm is to maximize net benefits (NB), which is equal to total benefits (TB) less total costs (TC). (i.e., NB=TB-TC). In order to obtain the marginal change, we can change the control variable, say, quantity of goods purchased, amount of goods actually produced, quantity of an input used, etc. Marginal analysis focuses upon whether the control variable should be increased/decreased by one more units or not. The two concepts through which the marginal analysis is done are marginal costs and marginal benefits. Marginal costs are the addition to total costs if one additional unit of the control variable is added. On the other hand, marginal benefits are the addition to the total benefits if the control variable increases by one additional unit. When the marginal benefit rise above marginal costs, the net benefits rise with every unit increase in the control variable. Therefore, more marginal units of the control variable should be added till the marginal costs and marginal benefits are equalized. On the other hand,

International Business in Emerging Markets Essay Example for Free

International Business in Emerging Markets Essay The global exchange of capital, goods and services also referred to as national trade is the pre-dominant part of all economies. Advancement in time of transportation, transnational corporations, globalization and outsourcing practices have led to the growth and importance of international trade (Anderson et al, 1993). This importance accrues from the amount of revenue this trade generates. The importance of this trade is apparent in the amount of money, time, human and other resources that go into the planning of global trade affairs (Bhagwati, 1992). Entire ministries and budgets are dedicated to prepare transnational trade efforts. Memberships to regional trade bodies such as the European Union receive higher priority than political alliances while negotiation of trade treaties takes more of the leadership’s time (Dixit et al, 1980). In addition to political envoys, governments have trade consuls in other nations (Mattli, 1999). It is thus alarming for a country to realize that her international trade position is not attaining the targets that would indicate prosperity. The UK is one of such whereby her deficit in goods and services has risen from 2. 2 to 3. 5 billion pounds between august and September 2009. The deficit with European Union countries widened in the same period. while that with non European countries replicated the downward trend. It is also reported that except for Oil and erratic commodities, the volume of exports in September was 0. 2 percent lower than the previous months with imports being higher by 4. 1 percent (ONS, 2009). This indicates an alarming trend which the concerned departments need to look into. Perhaps the downturn is due to external factors that might be within reach or not. However trade policy needs to be reviewed to check this spiral. This is especially to deal with identification of new global markets that can be used to add to the export tally thereby reducing the deficit. A look at theories of trade can assist in identifying new markets and potential angles that can be exploited to correct the adverse situation. International Trade Theories There are two broad themes in theories of international trade. The qualitative theories explain a countrys trade patterns, that is which products are traded and why. Instances are absolute advantage and comparative advantage. There are also quantitative theories that explain the terms of trade for instance relative prices of exports and imports in the trading activities. Changes in data such as factor supplies, technology, trade policy and global trends also come in as quantitative themes. More importantly in these quantitative analyses, there is consistent use of the general equilibrium (Dixit et al, 1980). The Mercantilist Theory. This is a qualitative theme in international trade. It postulates that while exporting is good for a country, importing is to be avoided. This rationale is based on the assumption of fact that revenue from exports is in gold standard currency. Thus accumulation of sufficient gold reserves can only be achieved through high rates of export. Mercantilism argued for close government regulation for two reasons: to maintain a favourable balance of trade thereby advancing aggressive export with restrictive import policies; and to promote the processing of raw materials at home instead of importing manufactured goods, which would distort production and employment at home. This is a classical theory that ignores not only the benefits of importing but also the reality that no country is self sufficient thus a need to import is inherent. An example of application is the Canadian Department of Foreign Affairs where Canadian traders have been informed that the Embassys mandate is to help exporters and non-disclosure of import relevant information. Absolute Advantage. Smith’s Theory of Absolute Advantage stated that countries should concentrate on producing what they are best at; that is products that they have absolute advantage in, Incentive to trade among countries is therefore created since each specializes in one product. Also as a classical theory, it is applicability is scant. In summary Smiths theory stated that unilateral trade liberalisation would be an advantageous policy for a country to follow, irrespective of the trade policies pursued by other countries. A drawback in Smiths postulation is if a nation has no absolute advantage over any of her potential trading partners with respect to any goods or services, then it means international trade is of no relevance to her (Dixit et al, 1980). Comparative Advantage Comparative advantage as developed by David Ricardo in his book, ‘The Principles of Political Economy’, is an improvement of the Absolute advantage theory. It declares that countries can trade without absolute advantage. They need comparative advantage where the relative cost of producing and exporting a product varies between trade partners. There are still benefits even if one trading partner is absolutely better in production. Comparative advantage has been the prevailing applied concept. It indicates that if two countries engage in trade, each will have the incentive to increase production, and decrease consumption, of goods in which it has the lower relative marginal cost prior to trade than the others. For instance if Britain has competitive equilibrium prices of 300 pounds per TV set and 4 pounds per bottle of whisky, while Japan has corresponding prices of 100000 and 2000 yen respectively, then ceteris peribus, if Britain produces one TV less then she would be able to utilise the freed resources to produce another 75 bottles of whisky. Japan on the other hand is able to produce one more TV set by freeing redeploying resources used to produce 50 bottles of whisky. It is to their mutual interest to do so since the pre-trade, relative price of a TV set is 50 bottles of whisky in Japan and 75 similar bottles in Britain. This is an inducement to Japan to expand TV production for export to Britain and import whisky from her. Presumably the relative price after commencement of trade will settle at between 50 and 75. The Ricardian Model assumes technology variations between nations. The assumptions in summary are: labor is the sole primary factor of production; Labor has constant returns; there is limited labor in respective economies; Mobility of labor across industries rather than countries; perfect competition situation. This theory has in modern times been reviewed to include intermediate goods, that is, capital goods for instance machinery thereby adjusting the labor only notion. These intermediate goods are tradable across countries in the current global situation (Dixit et al, 1980). Factors Endowment. Ricardos Comparative advantage theory was modified by Heckscher-Ohlin Theorem, also the Factor Proportions Hypothesis. Here a country should export products that are produced using factors that it is relatively well bestowed with. This is a separate theory but it also gives an explanation on the underlying factors as to comparative advantage. In each country, the factor that is relatively abundant is relatively cheaper. Also the good that is relatively intensive in using this factor this is relatively cheaper. Thus a country is expected to have comparative advantage in products that are intensive in the use of factors that are relatively abundant in supply. The H-O model assumed: inter sector factor mobility; distinction between labour and capital intensive; Factor variation between countries; free trade; and trans-country technology homogeneity. It however does not incorporate trade in intermediate goods. It was later challenged by the work of Wasilly Leontief who discovered that The US exported less capital intensive than it imported labour intensive products, also the Leontief’s paradox (Trebilcock et al, 2005). Contemporary Theories These include: the specific factors theory where in the short run mobility between industries in labor is possible and not possible in capital. It resembles a short run H-O model. If there is an increase in the price of a product then the owners of the factor specific to that product will profit in real terms; the new trade theory seeks to cater for the fact deficiencies of the two main approaches. That a lot of trade occurs between countries with identical factor of production endowment and the high level of multinational production, or foreign investment; the Gravity model that proffers an empirical analysis of international trade trends rather than the theoretical approaches detailed. It projects trade patterns on the basis of the distance between the nations and their economic size interaction. It imitates the law of gravity that factors distance and size. It considers factors such as levels of income, diplomatic ties and respective trade policy (Trebilcock et al, 2005). Emerging markets are nations described to be undergoing rapid growth and industrialisation in social and business activity. The concerned nations are usually said to be in a transition to fully developed status. Data on these countries has been compiled and a list of the top economics proffered. Examples of the dominant emerging economies are Brazil, Russia, India and China. They have been given the acronym, BRIC. Included are: Latin American countries such as Argentina; Asian countries such as South Korea; Russia in Eastern Europe; some in the Middle East; and parts of Africa for Instance South Africa. Lately though there have been shifts for instance Mexico has edged into the top four in terms of investment and development pushing ahead of Brazil. However China and India still dominate the list as the emerging markets with the best opportunities. As a factor of their GDP, population size, growth potential and level of imports (World Bank, 2000). These markets are characterised by robust economic growth, resulting in a rise in GDP and disposable income. Political and social stability is also an important indicator and condition for this categorisation. This implies that the population is able to purchase previously un-affordable goods and services . However quite a part of these countries population remain poor. International companies are presented with a large untapped market, providing them with an opportunity for market and financial growth. Luxury products such as high-end automobiles, designer clothing, and other Veblen goods benefit from such; but it is every day luxuries such as cell phones and brand name food products that reap the most from these markets.

The Difficulties of AIDS :: essays research papers

AIDS is a deadly disease that affects people world wide. AIDS is a disease that brings about many social consequences. Many of these consequences result in physical, emotional, and economic problems. AIDS compromises the immune system of the human body, making a person susceptible to many different illnesses and infections. Among these are: unexplained fatigue and weight loss, night sweats and flu-like feelings. These infirmities can interfere with a person’s daily physical tasks. For example, taking a shower, eating, working, excersing, caring for a child, and cooking. Being unable to perform these tasks makes an n individuals life extremely difficult. Individuals with AIDS also experience a number of emotional problems because of the social stigmas attached to AIDS. For instance, a person having to be scared to let others know he or she is infected, and being unable to engage in intimate relations without infecting others. Further emotional problems can be caused with the c ontinuous worry of death, which can inhibit a person’s normal functioning .People who have these issues develop a great deal of emotional problems because one feels that they do not fit into society. AIDS is not only a disease that affects an individual, but it also affects the larger society . This is so because of the financial needs to help fund programs and organizations to help stop the spread of AIDS and help those who suffer from AIDS. Although, the money goes towards helping AIDS victims it is costly for tax payers, when it can go towards helping people and developing educational programs within their communities. Why should the population pay for the bill for the consequences of others? As one can see, AIDS doesn’t only bring about consequences that indirectly affect individuals, but it also brings about consequences for society as well.   Ã‚  Ã‚  Ã‚  Ã‚   Every year, millions of people are infected and die from AIDS. This is because of ignorance, acts of choice, as well as religious beliefs. It is assumed that all people know the causes of AIDS, however, most people don’t know. Some people think that AIDS only afflicts homosexuals and drug abusers. This way of thinking displays that the government is not properly educating people on AIDS and prevention. A person who thinks in this manner feels that if they only have sex with a person that isn’t in an at risk group it is okay to have unprotected sex.

Communication Process Worksheet Essay

Think about a misunderstanding you have experienced with another person at work, school, or in a health care environment. Write your answers in paragraph form. 1. Briefly describe the misunderstanding, including the setting and the people involved. The misunderstanding I experienced was at work, when communication was crossed between me, my manager, and the Pathologist. I was told to do a certain project by the pathologist, and my manager had told me to get back to my desk and take phone calls. I had told my manager that I’m not supposed to be on the phone, because I’m doing a special project for the pathologist. The manager thought I was lying and she had to go talk to the pathologist that had advised me of the special project. It was later found out that I was to do the project after lunch when we usually don’t receive phone calls. 2. Complete the following table with information from your described misunderstanding. 3. The perception model in Ch. 2 of Communicating in the Workplace shows that prior knowledge and experiences combine with your psychological state to shape your subjective reality. What was your perception going into the situation? How did your perception of the misunderstanding affect the communication process? My perception going into the situation was that I had to start on the project right away and get it done as soon as possible. The project was my top priority. After I finish the project I would go back to my desk and continue my job tasks. My perception of the misunderstanding affected the communication process by not getting the job done when it should have been done. Thinking that I had to get on the project right away I forgot about my daily work tasks. Not doing my daily tasks would result in missed important phone calls and delayed tasks. With the misunderstanding I would have the wrong task done at the wrong times causing mishap and confusion. With missed phone calls there would be missed requests, concerns, and orders from our clients. The job would of not run smoothly that day. If communication was understood I would of completed my daily job tasks, then go on to finishing the project. 4. After reflecting on your misunderstanding and analyzing it with what you have learned this week, what did you learn about the communication process? What I learned about communication processes is the fact how a message is encoded or decoded to the sender and to the receiver, The way the communication process works out depends on how well the message is sent to the receiver. Reference Cheesebro, T., O’Connor, L., & Rios, F. (2010). Communicating in the workplace. Upper Saddle River, NJ: Prentice Hall.

Facilitation of Conditioned Fear Extinction

Neuroscience 134 (2005) 247–260 FACILITATION OF CONDITIONED FEAR EXTINCTION BY D-CYCLOSERINE IS MEDIATED BY MITOGEN-ACTIVATED PROTEIN KINASE AND PHOSPHATIDYLINOSITOL 3-KINASE CASCADES AND REQUIRES DE NOVO PROTEIN SYNTHESIS IN BASOLATERAL NUCLEUS OF AMYGDALA Y. L. YANGa AND K. T. LUb* Institute of Biotechnology, Department of Molecular Biology and Biochemistry, National Chia-Yi University, 300 University Road, Chia-Yi, Taiwan b Department of Life Science, National Taiwan Normal University, 88 Ming-Chow Road, Sec 4, Taipei, Taiwan aKey words: extinction, D-cycloserine, MAPK, PI-3 kinase, amygdala. Abstract—Recent results showed that either systemic or intra-amygdala administration of D-cycloserine, a partial agonist at the glycine modulatory site on the glutamate N-methylD-aspartate receptor facilitates the extinction of conditioned fear. Here we evaluated the role of mitogen-activated protein kinase and phosphatidylinositol 3-kinase in the basolateral nucleus of amygdala on the effect of D-cycloserine.The facilitation effect of D-cycloserine on fear extinction and mitogen-activated protein kinase activation was completely blocked by intra-amygdala administration of mitogen-activated protein kinase inhibitor PD98059 (500 ng/side, bilaterally) or U0-126 (20 M/side, bilaterally). Furthermore, phosphatidylinositol 3-kinase inhibitor (wortmannin, 5. 0 g/side, bilaterally) infused into the basolateral nucleus of amygdala signi? cantly reduced both facilitation effect of D-cycloserine and phosphatidylinositol 3-kinase activation.Intra-amygdala administration of a transcription inhibitor (actinomycin D, 10 g dissolved in 1. 6 l vehicle; 0. 8 l per side) and a translation inhibitor (anisomycin, 125 g dissolved in 1. 6 l vehicle; 0. 8 l per side) completely blocked the facilitation effect of D-cycloserine. Control experiments indicated the blockage by actinomycin D or anisomycin were not due to lasting damage to the basolateral nucleus of amygdala or state d ependency. In addition, none of the active drugs used here altered the expression of conditioned fear.These results suggested that phosphatidylinositol 3-kinase and mitogenactivated protein kinase-dependent signaling cascades and new protein synthesis within the basolateral nucleus of amygdala played important roles in the D-cycloserine facilitation of the extinction of conditioned fear.  © 2005 Published by Elsevier Ltd on behalf of IBRO. *Corresponding author. Tel: 886-2-29333149Ãâ€"234; fax: 886-229312904. E-mail address: [email  protected] ntnu. edu. tw (K. -T. Lu).Abbreviations: ACT DCS, actinomycin D D-cycloserine; ACT SAL, actinomycin D saline; ANI DCS, anisomycin D-cycloserine; ANI SAL, anisomycin saline; BLA, basolateral nucleus of the amygdala; CS, conditioned stimulus; DCS, D-cycloserine; EDTA, ethylenediaminetetraacetic acid; ISI, interstimulus interval; MAPK, mitogen-activated protein kinase; NMDA, N-methyl-D-aspartate; PD DCS, PD98059 D-cycloserine; PD SAL, PD9805 9 saline; PI-3K, phosphatidylinositol 3-kinase; US, unconditioned stimulus; U0 DCS, U0-126 D-cycloserine; U0 SAL, U0126 saline; VEH DCS, vehicle D-cycloserine; VEH SAL, vehicle saline; WH DCS, wortmannin D-cycloserine; WH SAL, wortmannin saline. 0306-4522/05$30. 00 0. 00  © 2005 Published by Elsevier Ltd on behalf of IBRO. doi:10. 1016/j. neuroscience. 2005. 04. 003 Fear conditioning occurs when a previously neutral stimulus (conditioned stimulus) is paired with an aversive stimulus (McAllister and McAllister, 1971).Following such pairing the conditioned stimulus is thought to elicit a state of conditioned fear. This is de? ned in animals by their behavior: freezing, autonomic reactivity, and fear-potentiated startle. A large literature indicates that the basolateral nucleus of the amygdala (BLA) is critically involved in both the acquisition and the expression of conditioned fear (Davis, 2000). Neurotoxic lesions or intra-amygdala infusion of glutamate antagonists into the BLA bl ocks the expression of conditioned fear. In addition, local infusion of N-methyl-D-aspartate (NMDA) speci? c antagonists blocks the acquisition of conditioned fear (Miserendino et al. , 1990; Kim et al. , 1991; Maren et al. , 1996; Gewirtz and Davis, 1997).Synaptic plasticity in this area is thought to underlie the learning process when afferent sensory information elicited by the conditioned stimulus is paired with afferent pain information elicited by the unconditioned stimulus (Fanselow and LeDoux, 1999). Extinction is de? ned as a reduction in conditioned fear when the conditioned stimulus (CS) is presented repeatedly in the absence of the unconditioned stimulus (US). Many studies show that extinction is not the result of forgetting or memory erasure but results from formation of new associations that compete with prior fear-conditioned associations (Falls and Davis, 1995; Davis et al. , 2000). Similar to acquisition, extinction is also blocked by glutamate NMDA receptor antagon ists either given systemically (Cox and Westbrook, 1994; Baker and Azorlosa, 1996; Kehoe et al. 1996) or locally infused into the BLA (Falls and Davis, 1992). The glycine modulatory site of the NMDA receptor provides a critical regulatory role. Whereas direct NMDA agonists may be neurotoxic due to unregulated calcium entry, partial agonists can facilitate glutamatergic NMDA activity in a more limited fashion (Lawler and Davis, 1992; Olney, 1994). Recent results showed that partial agonists acting at the glycine modulatory site of the NMDA receptor, such as D-cycloserine (DCS), enhance learning and memory in several animal models (Thompson and Disterhoft, 1997; Pussinen et al. , 1997; Matsuoka and Aigner, 1996; Land and Riccio, 1999; Walker et al. , 2002; 247 248 Y. L. Yang and K. T.Lu / Neuroscience 134 (2005) 247–260 extinction test, an extinction training and a post-extinction test (see Fig. 1A). Acclimation. On each of 3 consecutive days, rats were placed in the test chamb ers for 10 min and then returned to their home cages. Baseline startle test. On each of the next 2 consecutive days, animals were placed in the test chambers and presented with 30 95-dB startle stimuli at a 30-s interstimulus interval (ISI). Animals whose baseline startle response was 1% of the measurable level were not included in later analysis. Fear conditioning. Twenty-four hours later, rats were returned to the test chambers and after 5 min were given the ? rst of 10 light-footshock pairings.The shock (US) was delivered during the last 0. 5 s of the 3. 7 s light (CS). The average intertrial interval was 4 min (range 3–5 min) and the shock intensity was 0. 6 mA. Pre-extinction test. Twenty-four hours after fear conditioning, rats were returned to the test chambers and 5 min later presented with 30 startle-eliciting noise bursts (95 dB, 30 s ISI). These initial startle stimuli were used to habituate the startle response to a stable baseline prior to the light-noise test tr ials that followed. Thirty seconds later a total of 20 startle-eliciting noise bursts were presented, 10 in darkness (noise alone) and 10 3. 2 s after onset of the 3. s light (light-noise) in a balanced, irregular order at a 30-s ISI. Percent fear-potentiated startle was computed as [(startle amplitude on light-noise noise-alone trials)/noisealone trials] 100. Rats were then divided into equal size groups of comparable mean levels of percent fear-potentiated startle. Rats with less than 50% fear-potentiated startle during the pre-extinction test were not used. Extinction training. Extinction training (cue exposure) is de? ned as the repetitive exposure to the CS cue (light) in the absence of the US (shock). Twenty-four hours after the preextinction test, rats were returned to the test chamber. After 5 min, they were presented with 30, 3. s light exposures at a 30-s ISI. Context control groups (context exposure) remained in the test cages for the same amount of time but did not recei ve light presentations. Extinction training was performed for varying numbers of consecutive days (2 days for experiment 1 and 1 day for subsequent experiments). Post-extinction test-1. Twenty-four hours after the last extinction training, rats were returned to the test chamber. After 5 min, they were presented with 30 95-dB leader stimuli for a habituated startle baseline. This was followed by a total of 60 startle-eliciting noise bursts, 30 in darkness (noise alone) and 30 presented 3. 2 s after onset of the 3. s light (light-noise) in a balanced, irregular order at a 30-s ISI. Results were evaluated the same way as pre-extinction test. Post-extinction test-2. Twenty-four hours after the extend extinction training period, rats were returned to the test chamber and process the post-extinction test described above. Fear-potentiated startle test. Twenty-four hours after fear conditioning, rats were returned to the test chamber and testing for fear-potentiated startle using the post-e xtinction test-1 described above. Ledgerwood et al. , 2003; Richardson et al. , 2004). In addition, ( )-HA966, a competitive antagonist at the glycine regulatory site on the NMDA receptor, reversed the DCS effect (Walker et al. , 2002).Clinical studies have shown that DCS can sometimes enhance implicit memory and improve cognition in patients with Alzheimer’s disease (Schwartz et al. , 1996; Tsai et al. , 1998, 1999). It can also counter cognitive de? cits in schizophrenia (Javitt et al. , 1994; Goff et al. , 1999). Furthermore, systemic administration of DCS also proved to facilitate extinction of conditioned fear (Walker et al. , 2002; Ledgerwood et al. , 2003, 2004; Ressler et al. , 2004). Numerous signaling cascades including mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI-3K) and calcineurin, are involved in the extinction of conditioned fear (Lu et al. , 2001; Lin et al. , 2003).Similar mechanisms may also be involved in the facilitation effec t of DCS. This study was designed to clarify the relationship between amygdaloid NMDA receptors, MAPK and PI-3K signal cascades on the extinction of conditioned fear. EXPERIMENTAL PROCEDURES Animals Adult male Sprague–Dawley (SD) rats (obtained from the animal center of National Taiwan University Taipei, Taiwan) weighing between 250 and 350 g were used. Animals were housed in groups of four rats in a temperature (24  °C) -controlled animal colony with continuous access to food and water. Rats were kept on a 12-h light/dark cycle with lights on at 07:00 h. All behavioral procedures took place during the light cycle.All procedures were conducted in accordance with the National Institutes of Health Guide for Care and Use of Laboratory Animals and the guidelines set forth by the Institutional Animal Care and Use Committee at the National Taiwan Normal University. In all experimental procedures involving animals, all efforts were made to minimize pain and the number of animals u sed. Surgery All surgeries were carried out under sodium pentobarbital (50 mg/ kg, i. p. ) anesthesia. Once anesthetized, the rat was placed in a Kopf stereotaxic instrument, the skull was exposed, and 22 gauge guide cannula (model C313G, Plastic-one Products, Roanoke, VA, USA) were implanted bilaterally into the BLA (AP, 2. ; DV, 9. 0, ML, 5. 0 from bregma (Paxinos and Watson, 1997)). Size 0 insect pins (Carolina Biological Supply, Burlington, NC, USA) were inserted into each cannula to prevent clogging. These extended about 2 mm past the end of the guide cannula. Screws were anchored to the skull and the assembly was cemented in place using dental cement (Plastic-one Products). Rats received an antibiotic (penicillin) once every day for the ? rst 3 days after the surgery to reduce the risk of infection. General behavioral procedures Fear conditioning was measured using the potentiated startle paradigm (Cassella and Davis, 1986; Lu et al. , 2001; Walker et al. , 2002).The rats were trained and tested in a startle chamber (San Diego Instruments, San Diego, CA, USA) in which cage movement resulted in the displacement of an accelerometer. Startle amplitude was de? ned as peak accelerometer voltage within 200 ms after startle stimulus onset. The behavioral procedures common to all experiments consisted of an acclimation phase, a baseline startle test phase, a fear conditioning phase, a pre- Drug injection DCS (Sigma) was freshly dissolved in saline. DCS (15 mg/kg, i. p. ) or saline was injected intraperitoneally 15 min prior to extinction training with a 26 gauge injection needle connected to a 1 ml syringe (Walker et al. , 2002; Ledgerwood et al. , 2003) (experiments 1– 8).MAPK inhibitor PD98059 (500 ng in 1 l of 20% DMSO; Calbiochem) (Lu et al. , 2001) or U0-126 (50 ng/side; Sigma) (Lin et al. , 2003) or 20% DMSO was infused into the BLA Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 249 Fig. 1. Systemic administration of DCS accelerate d extinction of conditioned fear. (A) Timeline of behavioral procedures for experiment 1. (B) Percent fear-potentiated startle measured 24 h before (pre-extinction test) and 24 h after extinction training (post-extinction test). Rats in each group were treated with either DCS or saline prior to a single session of extinction training. (C) To test for toxicity, after 24 h all animals of experiment 1 were retrained.They were tested for fear-potentiated startle response in the absence of drugs 24 h later (fear-potentiated startle test) (values are mean SEM, * P 0. 05 versus control group; # P 0. 05 versus the group with 1 day extinction and saline injection). 250 Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 10 min prior to saline or DCS injection (experiments 2 and 8). PI-3K inhibitor (wortmannin, 5 g/side) (Lin et al. , 2003) or vehicle was administrated to the BLA 10 min prior to saline or DCS injection (experiment 3). Transcription inhibitor actinomycin D (10 g d issolved in 1. 6 l vehicle; 0. 8 l per side) or translation inhibitor (anisomycin, 125 g dissolved in 1. 6 l vehicle; 0. 8 l per side) or vehicle (Lin et al. 2003) was administrated to the BLA 10 min prior to DCS or saline injection (experiment 4) or 25 min prior to fear-potentiated startle test (experiment 6). In the control experiment, PD98059, U0-126, wortmannin, actinomycin D, and anisomycin were injected 25 min prior to the fear-potentiated startle test. Injections were made through 28-gauge injection cannula (model C313I, Plastic-one Products) connected to a Hamilton micro-syringe via polyethylene tubing. Infusion speed was 0. 25 l/ min. The total volume of injection was 0. 8 l per side. Western blot analysis Animals were killed by decapitation 10 min after extinction training. The lateral and basolateral subregions of the amygdala were collected and sonicated brie? y in ice-cold buffer: 50 mM Tris–HCl (pH 7. ), 50 mM NaCl, 10 mM EGTA, 5 mM EDTA, 2 mM sodium pyrophospha te, 4 mM para-nitrophenylphosphate, 1 mM sodium orthovanadate, 1 mM phenylmethylsulfonyl ? uoride (PMSF), 20 ng/ml leupeptin, and 4 ng/ml aprotinin. Following sonication, the soluble extract was obtained after pelleting the crude membrane fraction in a centrifuge at 50,000 g at 4  °C. Protein concentration in the soluble fraction was then measured using a Bradford assay with bovine serum albumin as the standard. Equivalent amounts of protein for each sample were resolved in 10% sodium dodecyl sulfate (SDS)–polyacrylamide gels, blotted electrophoretically to PVDF membranes and blocked overnight in 5% skim milk (Cell Signaling Technology, Inc. , USA).Blots were incubated with antiphospho-ERK antibody (New England Biolabs, USA), anti-ERK antibody (BD Transduction Laboratories, USA), anti-phospho-Akt antibody (New England Biolabs) or anti-pan-Akt (BD Transduction Laboratories). Band detection was performed with an enhanced chemiluminescence Western blotting analysis system (RPN 2108; Amersham International, Amersham, UK). fear-potentiated startle during the pre-extinction test. The ? nal 30 rats were assigned into ? ve groups of six animals based on their level of fear-potentiated startle in the preextinction test. Twenty-four hours after the pre-extinction test, each rat received 1 or 2 consecutive days of extinction training with DCS (15 mg/kg, i. p. ) or saline. Saline or DCS was injected 15 min prior to the extinction training.An additional control group was tested 2 days after the pre-extinction training without intervening exposures to visual CS. Fig. 1B shows that DCS accelerated extinction of conditioned fear. A two way ANOVA for differences in treatment (DCS vs saline) and days (one or two extinction sessions) between-subjects indicated a signi? cant treatment effect (F(1,20) 9. 02) and a signi? cant treatment days interaction (F(2,20) 6. 68). Thus, the reduction of fear-potentiated startle after 1 day of extinction training was greater in the gr oup that received DCS than in the group that received saline (Fig. 1B). Individual comparisons between DCS- and saline-treated groups indicated signi? ant differences after 1 day of extinction sessions (t(10) 3. 86). Previous studies have shown that lesions of the BLA block expression of fear-potentiated startle (Campeau and Davis, 1995). DCS may have toxic effect on BLA, and resulting misinterpretation of its facilitation effects on extinction. To test for toxicity, all animals of experiment 1 were retrained and tested 24 h later. Under these conditions, animals previously injected with DCS or saline showed a signi? cant fear-potentiated startle (Fig. 1C). Thus, the facilitation effect of DCS observed during the post-extinction test 1 appeared to result from the acute drug effect rather than from a more permanent, perhaps toxic, action of DCS.Experiment 2: intra-amygdala infusion of MAPK inhibitors blocked the facilitation of extinction by DCS To test the possible role of MAPK-depe ndent signaling cascade in the DCS-enhanced effect on the extinction of condition fear, 48 rats received fear conditioning, extinction training, and testing for fear-potentiated startle. Initially, 58 rats were used, but 10 of them were excluded. Rats were randomly assigned to six different groups and received one of the following treatments: vehicle saline (VEH SAL), vehicle DCS (VEH DCS), PD98059 DCS (PD DCS), U0-126 DCS (U0 DCS), PD98059 saline (PD SAL) or U0-126 saline (U0 SAL). The MAPK inhibitors, PD98059, and U0-126 (or vehicle) were administrated to the BLA 10 min prior to the injection with DCS or saline. Animals were then returned to their cage.Fifteen minutes after injection, animals were subjected to a single session of extinction training. Previously, we show that a single day of extinction training with cue exposure led to about 35% decrease in fear-potentiated startle, whereas 2–3 days of extinction training led to near complete extinction (Lu et al. , 2001; Wa lker et al. , 2002). We concluded that the acceleration of extinction is best detected after a single session of extinction training. As shown in Fig. 2, DMSO, PD98059 (500 ng/side, bilaterally), or U0-126 (20 nM/per side, bilaterally) was given 10 min prior to saline or DCS injection; rats were returned to their cages for 30 min before a single HistologyRats were overdosed with chloral hydrate and perfused intracardially with 0. 9% saline followed by 10% formalin. The brains were removed and immersed in a 30% sucrose-formalin solution for at least 3 day. Coronal sections (30 M) were cut through the area of interest, stained with Cresyl Violet, and examined under light microscope for cannula placement. Animals with misplaced cannula were not included in later analysis. Statistical analysis The mean startle amplitude across the 30 noise alone and 30 light-noise trials during the pre- and post-extinction tests was calculated for each animal. All results were analyzed using a score of percent fear-potentiated startle, as de? ned in the post-extinction tests above.ANOVA on scores was the primary statistical measure. Between-group comparisons were made using two-tailed t-tests for independent samples. The criterion for signi? cance for all comparisons was P 0. 05. RESULTS Experiment 1: systemic administration of DCS accelerated extinction of conditioned fear This experiment assessed the facilitation effect of DCS on different amounts of extinction training. Initially, 35 rats were used. Five were excluded for showing less than 50% Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 251 Fig. 2. Intra-amygdala infusion of MAPK inhibitors blocked facilitation effect of DCS on extinction. (A) Timeline of behavioral procedures for experiment 2. B) Cannula was placed in the BLA. Percent fear-potentiated startle measured 24 h before (pre-extinction test) and 24 h after extinction training (post-extinction test). Rats in each group underwent VEH SAL, VEH DCS, PD DCS, U0 DCS, PD SAL, or U0 SAL prior to a single session of extinction training. Twenty-four hours later, animals were tested for fear-potentiated startle in the absence of drugs (values are mean SEM, * P 0. 05 versus VEH SAL group; # P 0. 05 versus VEH DCS group). (C) Cannula tip placements transcribed onto atlas plates adapted from Paxinos and Watson (1997). 252 Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 session of extinction training.Twenty-four hours later, animals were tested for fear-potentiated startle in the absence of drugs. Results showed that there was a signi? cant overall difference between treatments (F(5,42) 11. 81). Fig. 2 shows that administration of DCS facilitated extinction of conditioned fear (VEH DCS) compared with the control group (VEH SAL) (t(14) 3. 12, P 0. 05). This effect was blocked by co-administration of MAPK inhibitor PD98059 (PD DCS) or U0-126 (U0 DCS) (t(14) 3. 08, P 0. 05 and t(14) 3. 29, P 0. 05, respectively) compared wit h the control (VEH DCS), treated with PD98059 only (PD SAL) or U0-126 only (U0 SAL) did not affect extinction (t(14) 0. 7 and t(14) 0. 36, respectively). These results indicated that the MAPK dependent signaling cascade most likely mediated the facilitation effect of DCS. Experiment 3: intra-amygdala infusion of the PI-3K inhibitor blocked facilitation of extinction by DCS Previous ? ndings have shown that PI-3K inhibitors retard acquisition in a variety of learning paradigms (Lin et al. , 2003). To evaluate the possible role of PI-3K signaling cascade in the DCS enhancement of extinction of conditioned fear, 32 rats received fear conditioning, extinction training, and testing for fear-potentiated startle. Although 38 rats were used initially, six were excluded.They were then randomly assigned to four different groups and received one of the following treatments: VEH SAL, VEH DCS, wortmannin DCS (WH DCS) and wortmannin saline (WH SAL). The PI-3K inhibitor (wortmannin, 5 g/side, bila terally) was infused to the BLA 10 min prior to the injection of saline or DCS. Then rats were returned to their cages for 15 min before being subjected to a single session of extinction training. Twenty-four hours later, animals were tested for fear-potentiated startle in the absence of drugs. Results showed that there was a signi? cant overall difference between treatments (F(4,28) 12. 17). As shown in Fig. 3, the facilitation effect of DCS (VEH DCS) on extinction was blocked by co-administration of PI-3K inhibitor (WH DCS) (t(14) 2. 98, P 0. 05).With the single extinction training session used in this experiment, this dose of wortmannin alone (WH SAL) at this dose had no effect on the extinction of fear-potentiated startle compared with control group (VEH SAL) (t(14) 0. 19). These results suggest that the PI-3K signaling cascade was involved in the DCS facilitation of extinction. Experiment 4: DCS enhanced the extinction training induced MAPK and PI-3K phosphorylation According t o the results of the above experiments, the DCS facilitation effect on extinction was prevented by coadministration of MAPK or PI-3K inhibitor. Previous studies have shown that infusion of these same inhibitors blocks extinction (Lu et al. , 2001; Lin et al. , 2003). Therefore, these treatments in conjunction with DCS must result in no extinction and resulting misinterpretation of its blockage effects on DCS.To show the MAPK and PI-3K signaling pathways are essential for the facilitation effect of DCS, we used Western blot to evaluate the DCS effect on the extinction training induced MAPK and PI-3K phosphorylation. Additional amygdala-cannulated rats received fear conditioning, extinction training, and testing for fear-potentiated startle. Then PD98059 or wortmannin was infused to the BLA 10 min prior to the injection of saline or DCS. Rats were returned to their cages. Fifteen minutes after DCS or saline injection, animals were subjected to a single session of extinction training. Animals were killed by decapitation 10 min after extinction training.The lateral and basolateral sub-regions of the amygdala were tested with Western blot analysis. Compared with control group, MAPK phosphorylation was signi? cantly elevated in BLA after extinction training (Fig. 4A, lane 2). Administration of DCS enhanced the effect of extinction training on MAPK phosphorylation (Fig. 4A, lane 3). The MAPK inhibitor PD98059 blocked the effect of DCS (Fig. 4A, lane 4). In addition, we measured the state of Akt phosphorylation as an index of PI-3K activity (Lin et al. , 2001). Fig. 4B showed that administration of DCS enhanced the effect of extinction training on Akt phosphorylation (Fig. 4B, lane 3). The PI-3K inhibitor, wortmannin, blocked the enhancement effect of DCS (Fig. 4b, lane 4).These results raise the possibility that DCS enhancement effect of extinction of conditioned fear is mediated by the amygdaloid MAPK and PI-3K dependent signaling cascades. Experiment 5: intra-amygd ala infusion of the transcription inhibitor or translation inhibitor blocked DCS facilitation of extinction The MAPK pathway participates in the synthesis of proteins important for the long-term stabilization and storage of fear memories. According to the result of experiment 2, the facilitation effect of DCS on extinction is mediated by the MAPK dependent signaling cascade. We predicted that the facilitation effect of DCS required new protein synthesis in the BLA.To test this hypothesis, 48 rats received fear conditioning, extinction training, and testing for fear-potentiated startle. Initially, 56 rats were used but eight of them were excluded. Rats were then randomly assigned to six different groups and received one of the following treatments: VEH SAL, VEH DCS, actinomycin D DCS (ACT DCS), anisomycin DCS (ANI DCS), actinomycin D saline (ACT SAL), and anisomycin saline (ANI SAL). Transcription inhibitor (actinomycin D, 10 g dissolved in 1. 6 l vehicle; 0. 8 l per side) and transl ation inhibitor (anisomycin, 125 g dissolved in 1. 6 l vehicle; 0. 8 l per side) were administered to the BLA 10 min prior to saline or DCS injection. Then rats were returned to their cages. Fifteen minutes later, nimals were subjected to a single session of extinction training. Twenty-four hours later, animals were tested for fear-potentiated startle in the absence of drugs. Results showed that there was a significant overall difference between treatments (F(5,42) 10. 17). As shown in Fig. 5, actinomycin D and anisomycin completely blocked the facilitation effect of DCS (t(14) 3. 11 and t(14) 2. 96, respectively) compared with the VEH DCS group. With a single extinction training session used in this experiment, actinomycin alone (ACT SAL) or anisomycin alone (ANI SAL) did not affect the extinction of fear-potentiated startle compared with control Y. L. Yang and K. T.Lu / Neuroscience 134 (2005) 247–260 253 Fig. 3. Intra-amygdala infusion of the PI-3K inhibitor blocked the fa cilitation effect of DCS on extinction. (A) Timeline of behavioral procedures for experiment 3. (B) Cannula was placed in the BLA. Percent fear-potentiated startle measured 24 h before (pre-extinction test) and 24 h after (post-extinction test) extinction training. Rats in each group were treated with VEH SAL, VEH DCS, WH DCS, or WH SAL prior to a single session of extinction training. Twenty-four hours later, animals were tested for fear-potentiated startle in the absence of drugs (values are mean SEM, * P 0. 05 versus VEH SAL group). C) Cannula tip placements transcribed onto atlas plates adapted from Paxinos and Watson (1997). 254 Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 (VEH SAL) (t(14) 0. 88 and t(14) 0. 48, respectively). These results suggest that new protein synthesis within the BLA played an important role in DCS facilitation of extinction of conditioned fear. Experiment 6: the disruptive effect of intra-amygdala infusion of actinomycin D and anisomy cin was not attributed to lasting damage to the amygdala The active drugs used in the above experiments may have toxic effect within the amygdala. Previous work shows that infusion of PD98095 (Lu et al. , 2001) or wortmannin (Lin et al. 2003) into BLA did not appear to cause permanent impairment of amygdala function. To test for possible toxic effects of actinomycin D and anisomycin on the BLA, all animals of experiment 5 received an additional 2 days of drug free extinction training followed 24 h later by testing. Under these conditions, rats previously treated with actinomycin D (ACT DCS-treated group and ACT SALtreated group) or anisomycin (ANI DCS- and ANI SALtreated group) showed a signi? cant reduction of fearpotentiated startle between post-extinction test 1 and post-extinction test 2 (t(7) 3. 08 and t(7) 3. 32 for the ACT DCS-treated group and ACT SAL-treated group respectively) and (t(7) 2. 96 and t(7) 3. 1 for the ANI DCStreated group and ANI SAL-treated group respectively ) (Fig. 6B). Thus, the blockage of extinction observed during post-extinction test 1 appeared to result from an acute drug effect rather than from a more permanent and perhaps toxic action, of actinomycin D or anisomycin. Previous studies have shown that lesions of the BLA block fear-potentiated startle (Campeau and Davis, 1995), an outcome opposite from that obtained with infusion of actinomycin D or anisomycin. It is also important to note that actinomycin D or anisomycin may have long-term toxicity within the BLA. The extinction of fear would look the same as a gradual loss of ability to express or relearn fear.Experiment 7: the disruptive effect of intra-amygdala infusion of actinomycin D and anisomycin was not attributed to state dependency To evaluate the contribution of state-dependency effects to the results obtained in experiment 6, additional amygdala-cannulated rats were tested for extinction in a drug-free state and after receiving the same compound that they had receive d during extinction training. Results showed that there was a signi? cant overall difference between treatments in post-extinction test 2 (F(2,21) 32. 16). These results are shown in Fig. 7. Rats infused with actinomycin or anisomycin before postextinction test 2 showed a slight, but non-signi? cant, decrease in fear-potentiated startle from post-extinction test 1 to post-extinction test 2. For control rats (n 8), fear-potentiated startle was signi? cantly lower during post-extinction test 2 than post-extinction test 1 (t(7) 2. 455; P 0. 05). The lost of fear-potentiated startle in both groups probably re? cted incidental extinction produced by the 30 non-reinforced CS presentations of post-extinction test 1. The failure of rats infused before Fig. 4. MAPK and PI-3K inhibitors blocked extinction training activation of MAPK and PI-3K. (A) Representative Western blots and densitometric analysis of the activation of MAPK in the BLA under different treatments (values are mean SEM, * P 0 . 05 versus VEH SAL group). (B) Representative Western blots and densitometric analysis Akt phosphorylation as an index of PI-3K activity in the BLA under different treatments (values are mean SEM, * P 0. 05 versus VEH DCS group). Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 255 Fig. 5.Intra-amygdala infusion of the transcription inhibitor or translation inhibitor blocks the facilitation effect of DCS on extinction of conditioned fear. (A) Timeline of behavioral procedures for experiment 5. (B) Cannula was placed in the BLA. Percent fear-potentiated startle measured 24 h before (pre-extinction test) and 24 h after (post-extinction test 1) extinction training. Rats underwent treatment with VEH SAL, VEH DCS, ACT DCS, ANI DCS, ACT SAL, or ANI SAL prior to a single session of extinction training. Twenty-four hours later, animals were tested for fear-potentiated startle in the absence of drugs (values are mean SEM, * P 0. 05 comparing with the VEH SAL group; # P 0. 05 compared with the VEH DCS group). C) Cannula tip placements transcribed onto atlas plates adapted from Paxinos and Watson (1997). 256 Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 Fig. 6. The disruptive effects of intra-amygdala infusion of actinomycin D and anisomycin on extinction were not attributed to lasting damage to the BLA. (A) Timeline of behavioral procedures for experiment 6. The same animals used in experiment 3 were subjected for two more trials of extinction training. (B) Twenty-four hours after the last extinction training, animals were tested for fear-potentiated startle in the absence of drugs (post-extinction test-2) (values are mean SEM, * P 0. 05 versus the corresponding post-extinction test-2). esting with the transcription and translation inhibitors before testing to show a loss of fear-incidental extinction suggested that state dependency was not a major factor in the effects of actinomycin D and anisomycin. Experiment 8: effect of pretest PD98059, U0-126, wortmannin, actinomycin, and anisomycin administration on fear-potentiated startle This experiment was designed to evaluate whether the effect of the active drugs used has had a secondary effect on fear itself or on CS processing. For example, if MAPK inhibitor U0-126 reduced CS-elicited fear, this might attenuate extinction by decreasing the discrepancy between CS predictions and what actually occurred. If actinomycin D or anisomycin interfered with visual processing, this might block extinction produced by non-reinforced exposures to the visual CS.To evaluate these possibilities, 42 amygdala-cannulated rats received acclimation, baseline startle test, and fear conditioning. Initially, 50 rats were used, but eight of them were excluded. After 24 h, rats were infused with PD98059, U0-126, wortmannin, actinomycin, and anisomycin. At 25 min after the infusions, rats were tested for fear-potentiated startle. As shown in Fig. 8, none of the active drugs we used here sig ni? cantly in? uenced fearpotentiated startle (F(6,35) 0. 993). Thus, it is unlikely that these drugs in? uenced extinction by increasing fear or by disrupting CS processing. Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 57 Fig. 7. The disruptive effect of intra-amygdala infusion of actinomycin D and anisomycin were not attributed to state dependency. (A) Timeline of behavioral procedures for experiment 7. (B) Cannula was placed in the BLA. Percent fear-potentiated startle measured 24 h before (pre-extinction test), 24 h after (post-extinction test 1), and 48 h after (post-extinction test 2) extinction training. Rats in each group underwent VEH SAL, ACT DCS, or ANI DCS prior to a single session of extinction training and prior to post-extinction test 2. Animals were tested for fear-potentiated startle in the absence of drugs (values are mean SEM, * P 0. 05). C) Cannula tip placements transcribed onto atlas plates adapted from Paxinos and Watson (1997). 258 Y. L. Y ang and K. T. Lu / Neuroscience 134 (2005) 247–260 Fig. 8. Effect of pretest PD98059, U0-126, wortmannin, actinomycin, and anisomycin administration on fear-potentiated startle. (A) Timeline of behavioral procedures for experiment 8. (B) Cannula was placed in the BLA. Percent fear-potentiated startle was measured 24 h after fear conditioning. Rats were treated with DMSO, PD98059 (PD), U0-126 (U0), wortmannin (WH), vehicle (VEH), actinomycin (ACT), or anisomycin (ANI) 25 min prior to the fear-potentiated startle test (values are mean SEM). C) Cannula tip placements transcribed onto atlas plates adapted from Paxinos and Watson (1997). DISCUSSION We build on the previous ? ndings that DCS facilitated extinction of conditioned fear (Walker et al. , 2002; Ledgerwood et al. , 2003, 2004; Ressler et al. , 2004). Here, we show for the ? rst time that the DCS effect was prevented by co-administration of MAPK, PI-3K, transcription, and translation inhibitors. Control experiments indica ted that the blocking effects of actinomycin D and anisomycin on extinction were not due to lasting damage to the BLA or state dependency. In addition, none of active drugs we used in this study altered the expression of conditioned fear.These results suggest that PI-3K and MAPK-dependent signaling cascades and de novo protein synthesis within the BLA were important for DCS facilitation. Early behavioral studies by Pavlov (1927) and Konorski (1948) de? ned extinction as an active process involving formation of new inhibitory associations as opposed to forgetting previously conditioned associations. Numerous studies since have con? rmed and elaborated these early ? ndings (reviewed in Falls and Davis, 1995; Davis et al. , 2000). It is now well accepted that extinction occurs with repeated presentation of a CS in the absence of the pre- Y. L. Yang and K. T. Lu / Neuroscience 134 (2005) 247–260 259 viously paired US.This reduces the conditioned response elicited by the CS. In co ntrast to forgetting which implies the passive loss of memory, extinction implies active formation of new inhibitory associations competing with and overpowering original excitatory associations. Evidence is growing that extinction may involve circuits and use mechanisms of synaptic plasticity similar to those of conditioned fear learning (Falls and Davis, 1992; Cox and Westbrook, 1994; Baker and Azorlosa, 1996; Davis et al. , 2000). NMDA-dependent synaptic plasticity appears to mediate many forms of active learning (Morris, 1989; Staubli et al. , 1989; Flood et al. , 1990; Collinridge and Bliss, 1995).It is likely that conditioned fear learning depends on CS–US pairing mediated by NMDA receptors within the BLA (Miserendino et al. , 1990; Fanselow and LeDoux, 1999). Extinction also appears to require active, NMDA-dependent learning within the amygdala. This was demonstrated by blockage of extinction by microinjections of APV into the BLA in both fear-potentiated startle (Fall s and Davis, 1992) and freezing paradigms (Lee and Kim, 1998). Furthermore, systemic administration of a different NMDA antagonist, MK801, blocks the extinction process in a range of different learning paradigms (Cox and Westbrook, 1994; Baker and Azorlosa, 1996; Kehoe et al. , 1996).Recently, DCS, a partial agonist acting at the strychnine-insensitive glycine-recognition site of the NMDA receptor complex, has repeatedly been shown to facilitate learning in various cue and context association paradigms (Monahan et al. , 1989; Flood et al. , 1992; Thompson and Disterhoft, 1997). Walker et al. (2002) reported the ? rst evidence that DCS facilitates extinction of learned fear. Since then, further studies con? rmed and elaborated this early ? nding (Ledgerwood et al. , 2003, 2004; Ressler et al. , 2004). These studies reported that DCS is more effective at facilitating extinction when given after extinction training, rather than before. They interpret these ? dings as evidence that DCS facilitates the consolidation of a new memory acquired during extinction. It is important to note that although some studies have shown DCS to be effective in improving memory impairment due to Alzheimer’s disease (Schwartz et al. , 1996; Tsai et al. , 1999) and schizophrenia (Javitt et al. , 1994; Goff et al. , 1999), other studies found little or no improvement (Tsai et al. , 1998; van Berckel et al. , 1999). This may be related to the fact that acute treatment with DCS may have a more pronounced facilitation than chronic treatment (Quartermain et al. , 1994; Ledgerwood et al. , 2003; Richardson et al. , 2004). Ledgerwood et al. (2003, 2004) reported that DCStreated animals fail to exhibit reinstatement effects.That DCS enhances extinction may be through some processes different from extinction induced by repeat representation of CS. Lin et al. (2003) investigated the similarities and differences between consolidation of conditioning and consolidation of extinction. They fo und that both processes depend on activation of NMDA receptors, PI-3K, MAPK, and require synthesis of new proteins within the amygdala. They also found that different characteristics show differential sensitivity to the transcription inhibitor actinomycin D. Our results were consistent with the model that the extinc- tion process involved active learning of new inhibitory associations.Here we showed that DCS facilitation of extinction could be blocked by actinomycin D and anisomycin. These seemingly con? icting results could be attributable to our extinction protocol. Our protocol resembled betweensession extinction, presumably corresponding to long-term extinction memory. In addition, we used DCS to facilitate the extinction process and tested the animals in a drug free condition. Acquisition or consolidation of long-term memory requires activation of protein kinase, transcription of genes, new protein synthesis, and synapse formation (Schafe and LeDoux, 2000). Similar mechanisms w ere involved in the DCS facilitation of extinction. The DCS activated NMDA receptors, resulted in Ca2 in? x into the cell, and led to the PI-3K and MAPK activation. Activated MAPK can translocate to the nucleus, subsequently activating transcription factors to promote gene transcription and new protein synthesis. Thus, combinations of drugs and extinction training may weaken or erase original memory. There is increasing evidence that learning of CS–US associations involves synaptic plasticity within the BLA, leading to differential activation of this circuit by sensory afferents (Davis, 1997; Rogan et al. , 1997; Lee and Kim, 1998; Fanselow and LeDoux, 1999). 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