Monday, May 25, 2020

Hamlet, By William Shakespeare - 1431 Words

In Shakespeare’s play â€Å"Hamlet,† we are introduced to the sorrow and tragic character of Ophelia. In spite of a comparatively marginal role throughout the play, Ophelia actually has quite a substantial impact on our understanding of the main character, Hamlet. With Ophelia’s highly controversial and often debated death, we are left to ponder about what truly constitutes action, attempting to make meaning of actions with relation to context. Specifically, through examining Gertrude’s description of Ophelia’s death, while also taking into consideration the character’s history and experiences, we can forge a connection between our understanding of Ophelia’s actions, and Hamlet’s dilemma with his own actions. To unravel the reality of†¦show more content†¦From this depiction of the incident and the introduction of a spiteful branch that broke, we are given the perception that Ophelia’s decision to climb the branc h was a miscalculated one purely for the intention of hanging her flowers, as opposed to it being the grounds of her suicide. This is supported with Gertrude description that after the branch broke, â€Å"down her weedy trophies and herself [Ophelia] Fell in the weeping brook† (4.7.174-75). From Gertrude’s choice of diction, considering her use of the word â€Å"fell,† instead of, perhaps, â€Å"jumped,† one is provided with an image of a young girl falling to her death, merely for lack of better judgment, and not a contrived suicide. Controversy is created as Gertrude recounts what happened next in how Ophelia â€Å"chanted snatches of old lauds,† rather than attempting to swim out of the stream; appearing â€Å"as one incapable of her own distress† (4.7.177-78). This could suggest that Ophelia is, in fact, committing suicide, as otherwise her reflex action after a fall would see her struggle to swim out. Yet, by factoring her character and state of mind, a more plausible explanation may be that she was blinded by her insanity, and unaware of her menacing circumstances in the stream. While no conclusive verdict can be made, Gertrude inclines us to conclude an accident as a higher probability to what took the life of this troubled woman. By close reading of Gertrude’s passage, emphasizing Ophelia’s

Thursday, May 14, 2020

The Iconic Egg-and-Dart Motif

Egg-and-dart is a repetitive design that today is most often found on molding (e.g., crown molding) or trim. The pattern is characterized by a repetition of oval shapes, like an egg split lengthwise, with various non-curved patterns, like darts, repeated between the egg pattern. In three-dimensional sculpting of wood or stone, the pattern is in bas-relief, but the pattern can also be found in two-dimensional painting and stencil. The curved and non-curved pattern has been pleasing to the eye for centuries. It is often found in ancient Greek and Roman architecture and, so, is considered a Classical design element. Definition of Egg-and-Dart Egg-and-dart molding is a decorative molding in classical cornices that resembles alternating egg-shaped ovals with downward-pointing darts. — John Milnes Baker, AIA Egg and Dart Today Because its origins are from ancient Greece and Rome, the egg-and-dart motif is most often found in Neoclassical architecture, both public and residential, on interiors and exteriors. The Classical design provides a regal and stately feel to a room or facade. Examples of Egg-and-Dart The above photos illustrate the common ornamentation use of egg-and-dart design. The top photo is a detail of an Ionic column of the Great Court at the British Museum in London, England. This columns capital shows the volutes or scrolls typical of Ionic columns. Although the scrolls are a defining characteristic of the Ionic Classical Order, the egg-and-dart between them are added details—architectural ornamentation more ornate than found on many earlier Greek structures. The bottom photo is a piece of cornice from the Roman Forum in Italy. The egg-and-dart design, which would run horizontally along the top of the ancient structure, is underscored by another design called bead and reel. Look carefully at the Ionic column in the picture above, and youll notice the same bead-and-reel design beneath that egg-and-dart. In the egg-and-dart design on the ancient Parthenon in Athens, Greece combines both of these uses—between volutes and continuous design line on the entablature. Other Roman-inspired examples include the Temple of Saturnus at the Roman Forum in Italy and the Temple of Baal in Palmyra, Syria. What is Ovolo? Ovolo molding is another name for quarter round molding. It comes from the Latin word for egg, ovum, and is sometimes used to describe crown molding decorated with an egg-and-dart motif. Ensure that you understand the meaning of ovolo as used by your architect or contractor because todays ovolo molding does not necessarily mean its decoration is egg-and-dart. So, what is ovolo? A convex molding less than a semi-circle in profile; usually a quarter of a circle or approximately a quarter-ellipse in profile.—Dictionary of Architecture and Construction Other Names for Egg and Dart (with and without hyphens) egg and anchoregg and arrowegg and tongueechinus What Is Echinus and Astragal? This design looks very similar to egg-and-dart with a bead and reel below. The word echinus, however, is architecturally part of a Doric column and the word astragal describes a bead design more simple than bead and reel. Today, echinus and astragal is used by historians and students of Classical architecture—rarely by homeowners. Sources Baker, John Milnes, and W.W. Norton, American House Styles: a Concise Guide. 1994, p. 170.Harris, Cyril M. Dictionary of Architecture Construction. McGraw-Hill, 2006. pp. 176, 177, 344.

Wednesday, May 6, 2020

Poes Heart Essay - 1456 Words

Edgar Allan Poe is one of the most recognized prose poets, short story authors, and literary composers of all time. His works contain trending themes such as love, time, death and the concept of â€Å"oneness.† Poe often expressed these themes according to events that he had experienced, and some of his themes intertwined with others. Take for instance, his love for beauty and perfection played a major role in his concept of oneness, or state of absolute fulfillment. However in his short story, The Tell-Tale Heart, Poe effectively explores the power of guilt, and leads his readers through a cynical plot to murder while enduring the struggle to silence a beating conscience by treading the lines of genius versus insanity, moral reasoning versus†¦show more content†¦So while his ideas of truth and fiction â€Å"mingled† with one another to be exposed on paper, his inability to carefully distinguish the two is what added timelessness to The Tell-Tale Heart. Debatin g and deciphering the difference between an absolute intellect and an absolute sociopath is one investigation that never grows old. Poe’s writing not only treads the line of genius and insanity, but he balances the two in a way that leaves each reader with the opportunity to form his/her own conclusion of the narrator. Now, this story also blurs the line between moral reason and indifferent resolution. In the opening excerpts of the story, the narrator explains that he indeed loved the old man. The old man â€Å"never wronged nor insulted him.† But the feeling that he felt towards the old man’s eye was something so overwhelming, it shadowed any moral reasoning he could ever imagine. He explains that his blood ran cold whenever he looked at it. So this caused him to compute an indifferent resolution: kill the old man, and he’d no longer have to witness the chilling eye. He still remained kind to the old man after resolving to kill him. Although it seems that he would behave this way based on his moral reason, the idea actually stemmed from his indifferent resolution. He wanted to make sure the old man had no idea of his sinister plot, so he treated him well before executing his demise. OftenShow MoreRelatedEdgar Allan Poes The Tell Tale Heart1203 Words   |  5 PagesA Tell-Tal e Spirit In 1843, author Edgar Allan Poe crafted a haunting story about a man who commits murder because he finds an old mans’ pale eye unsettling. This story, â€Å"The Tell-Tale Heart†, is one of many masterfully written stories crafted by the gifted writer. Edgar Allan Poe was born on January 19th, 1809, in Boston, Massachusetts but was orphaned at the young age of three. His foster parents surrounded him with material comfort in the city of Richmond, Virginia. As a youth, Poe excelledRead MoreSymbolism In Edgar Allen Poes The Tell Tale Heart1174 Words   |  5 Pagesdoes it make it more or less important? Symbolism is used to represent ideas; that may imply deeper, hidden meaning than what the text directly states. Symbolism can be used in different ways throughout different books; for example, â€Å"The Tell-Tale Heart†, by Edgar Allen Poe and â€Å"Once upon a Time†, by Nadine Gordimer, contain a variety of symbolism that have the possibility of hav ing two or more meanings. The problem with this is identifying what the text could really mean, and how that changes theRead MoreThe Murderers Motivation Depicted in Poes The Tell-Tale Heart1820 Words   |  8 PagesPoes writings are not without morals, and as a representation of a guilty conscience, â€Å"The Tell-Tale Heart† has been called one of the most effective parables ever conceived (Ward 310). â€Å"I find it almost impossible to believe that Poe has no serious or artistic motive in The Tell-Tale Heart, that he merely revels in horror and only inadvertently illuminates the depths of the human soul,† James Gargano asserts. He further states that though Poes stories sometimes seem to be nothing more than ramblingsRead More Critical Analysis of Poes The Tell Tale Heart Essay examples1635 Words   |  7 PagesCritical Analysis of Poes The Tell Tale Heart The Tell Tale Heart is a story, on the most basic level, of conflict. There is a mental conflict within the narrator himself (assuming the narrator is male). Through obvious clues and statements, Poe alerts the reader to the mental state of the narrator, which is insanity. The insanity is described as an obsession (with the old mans eye), which in turn leads to loss of control and eventually results in violence. Ultimately, the narrator tellsRead MoreSymbolism in Edgar Allen Poes The Tell-Tale Heart Essay863 Words   |  4 PagesSymbolism in Edgar Allen Poes The Tell-Tale Heart In Poes The Tell-Tale Heart, the narrator claims that he is not mad but his behavior tells a different story. He is truly determined to destroy another male human being, not because of jealousy or animosity but because one of his eyes resembled that of a vulture- a pale blue eye, with a film over it (1206). The narrator sees the man with this ghastly eye as a threat to his well being, but it is he who is a menace to his own being. HeRead MoreA Reader- Oriented Approach to Edgar Alan Poes the Tell- Tale Heart1465 Words   |  6 Pagesâ€Å"If a tree falls in the forest and no one hears it, does it make a sound?† A Reader- Oriented approach to Edgar Alan Poe’s The Tell- Tale Heart The Titular question is an old philosophical riddle for which a wide range of metaphysical and non-metaphysical solution has been offered. The answers differ based on the perspective of the interpreter. Judging these answers is neither possible nor desirable for us, but the riddle and the ensuing debates attest to the veracity of one of the mostRead More Edgar Allen Poes The Tell Tale Heart Essay499 Words   |  2 PagesIn The Tell-Tale Heart, by Edgar Allen Poe, the setting, the plot, the characters and even the point of view are great contributing factors to the overall reaction of the readers of the narrative. The setting contributes to the readers reaction in several different ways. All of the shutters in the house were closed, no one could see anything from the outside or the inside. This was important because no one ever knew what went on in the house except the old man with the pale blue eye with a filmRead MoreEssay on Creating Suspense in Edgar Allen Poes The Tell-Tale Heart2319 Words   |  10 PagesCreating Suspense in Edgar Allen Poes The Tell-Tale Heart In the gothic genre there are numerous techniques the author can use to add interest and suspense to a story, such as the choice of words, the time of day and pathetic fallacy, to name but a few. In the Tell Tale- Heart Poe uses psychosis, detail, and appeal to the reader to keep us on the edge of our seats. These are just some examples of what makes the story so thrilling. The story is written in the first person in the styleRead More Comparing Edgar Allen Poes The Cask of Amontillado, The Black Cat, and The Tell-tale Heart752 Words   |  4 PagesComparing Edgar Allen Poes The Cask of Amontillado, The Black Cat, and The Tell-tale Heart The short stories of Edgar Allen Poe demonstrate the authors ample gifts in the psychology of the mind, regardless of the fact he was decades ahead of Freud.   Poes short stories are often from the deranged and murderous point-of-view of the narrator, who often illustrates the inner-workings of his own psychology and the disintegration of the self brought about by psychological disorders, aberrationsRead MoreFreudian Analysis of Edgar Allen Poes a Tell Tale Heart Essay665 Words   |  3 PagesErika Barnett Professor Curley Daring the Nightmare 13 October 2010 A Freudian Analysis of â€Å"The Tell-Tale Heart† By Edgar Allen Poe As an esteemed psychologist analyzing this accused murderer, I have found a few key pieces of evidence that ultimately lead me to the decision that the murderer is in fact mad and I recommend psychological rehabilitation as well as jail sentence as a proper penalty for the crime committed. Although, he claims he can recount the night of the murder â€Å"healthily and

Tuesday, May 5, 2020

Romeo Juliet the tension in Act 3 Scene 1 Essay Example For Students

Romeo Juliet: the tension in Act 3 Scene 1 Essay * Romeo and Juliet was written by William Shakespeare in the 1500s, and is the story of two star-cross lovers from two rival families who find love with one another amongst the hate and violence between their two families. * The play belongs to the genre of plays known as tragedies, and more specifically, belongs to Romantic Tragedy, a genre Shakespeare created, and started off with this very play. Romeo and Juliet is a tragedy as the two main characters (Romeo and Juliet), die at the end of the play. * The main themes of the play: Love, Destiny, Power, Honour, Masculinity and Manhood. * Socio-historical Context: Male Dominance, Arranged Marriage, Plague, City of Verona-City associated with hot-blooded people. Act 1 Scene 1: * The Elizabethan society was strongly male-dominant, and men had the role of the breadwinner, the person who works and earns income. Women were thought of as mothers and child bearers and were considered subservient to men. Masculinity is a key theme of this scene- servants show off and boast I strike quickly to be moved. Thrust his maids to the wall. * Shakespeare contradicts this widely-held belief of the time in Act 1 Scene 1, where he portrays the wives of Lord Capulet and Lord Montague as being very strong, powerful women, who prevent their husbands from going to war. Crutch! A crutch! Shakespeare could have portrayed them in such a way as he feels that society needs to be rid of these stereotypes, and could have tried to convey this message to his audience in this way, trying to get them to question the male dominancy in society. . Shakespeare could have believed that this view was outdated and that men were just arrogant and irrational. Also, it could be said that Shakespeare merely wanted to show this powerful role of women to appease Queen Elizabeth I, who ruled England during Shakespeares lifetime. * The groundlings of the audience were peasants and poor servants. In this scene, Shakespeare shows the Lords and Ladies of Verona to be arrogant and uncaring, whilst the servants are hard-working and loyal to their masters despite being treated unfairly. Shakespeare would have done this to please the groundling crowd, and send a message to the Upper and Middle Classes that they need to change their attitudes and behaviour. * This first scene is also very aggressive and loud, and is used to hook the audience into the play. A large amount of violence is used, with loud arguments and fighting, which draws the audience in and grabs their attention straight away. Act 3 Scene 1: * Shakespeare structures the play in an oxymoron form. The previous scene to Act 3 Scene 1 is very peaceful, and is when Romeo and Juliet get married. The scene is very sweet and calm. This atmosphere is turned on its head and is contrasted sharply with the very tense and violent scene of Act 3 Scene 1. Shakespeare does this to draw in the attention of the audience, and to show the contrast between love and hate, a very core theme of the play. * Shakespeare highlights the faults of the upper-class, and more importantly, of men in this scene. The fight between Mercutio and Tybalt which lead to both of them being killed was caused by the simple fault of arrogance, and the need for upper-class men to live upto their reputation, their manhood, and their need to compete for power. This could have reflected the social situation at the time, and Shakespeare could have been trying to send a message to these men in the upper class of society that their boisterous ways can only lead to unfortunate outcomes. .udeb86bca0f77bc1ac52b85aa05513c75 , .udeb86bca0f77bc1ac52b85aa05513c75 .postImageUrl , .udeb86bca0f77bc1ac52b85aa05513c75 .centered-text-area { min-height: 80px; position: relative; } .udeb86bca0f77bc1ac52b85aa05513c75 , .udeb86bca0f77bc1ac52b85aa05513c75:hover , .udeb86bca0f77bc1ac52b85aa05513c75:visited , .udeb86bca0f77bc1ac52b85aa05513c75:active { border:0!important; } .udeb86bca0f77bc1ac52b85aa05513c75 .clearfix:after { content: ""; display: table; clear: both; } .udeb86bca0f77bc1ac52b85aa05513c75 { display: block; transition: background-color 250ms; webkit-transition: background-color 250ms; width: 100%; opacity: 1; transition: opacity 250ms; webkit-transition: opacity 250ms; background-color: #95A5A6; } .udeb86bca0f77bc1ac52b85aa05513c75:active , .udeb86bca0f77bc1ac52b85aa05513c75:hover { opacity: 1; transition: opacity 250ms; webkit-transition: opacity 250ms; background-color: #2C3E50; } .udeb86bca0f77bc1ac52b85aa05513c75 .centered-text-area { width: 100%; position: relative ; } .udeb86bca0f77bc1ac52b85aa05513c75 .ctaText { border-bottom: 0 solid #fff; color: #2980B9; font-size: 16px; font-weight: bold; margin: 0; padding: 0; text-decoration: underline; } .udeb86bca0f77bc1ac52b85aa05513c75 .postTitle { color: #FFFFFF; font-size: 16px; font-weight: 600; margin: 0; padding: 0; width: 100%; } .udeb86bca0f77bc1ac52b85aa05513c75 .ctaButton { background-color: #7F8C8D!important; color: #2980B9; border: none; border-radius: 3px; box-shadow: none; font-size: 14px; font-weight: bold; line-height: 26px; moz-border-radius: 3px; text-align: center; text-decoration: none; text-shadow: none; width: 80px; min-height: 80px; background: url(https://artscolumbia.org/wp-content/plugins/intelly-related-posts/assets/images/simple-arrow.png)no-repeat; position: absolute; right: 0; top: 0; } .udeb86bca0f77bc1ac52b85aa05513c75:hover .ctaButton { background-color: #34495E!important; } .udeb86bca0f77bc1ac52b85aa05513c75 .centered-text { display: table; height: 80px; padding-left : 18px; top: 0; } .udeb86bca0f77bc1ac52b85aa05513c75 .udeb86bca0f77bc1ac52b85aa05513c75-content { display: table-cell; margin: 0; padding: 0; padding-right: 108px; position: relative; vertical-align: middle; width: 100%; } .udeb86bca0f77bc1ac52b85aa05513c75:after { content: ""; display: block; clear: both; } READ: Jonh Keats Essay* At the beginning of the scene, the atmosphere is quite relaxed, yet tense and agitated, due to the scorching heat of the day, and the restlessness of Mercutio. When Tybalt enters the scene, things suddenly become extremely tense; with the hot weather and the agitation adding to the effect (This is called Pathetic Fallacy). * Shakespeare uses dramatic Irony to create tension in this scene. The audience and Romeo know why Romeo cannot fight Tybalt, but the other characters do not. Romeo is now married to Juliet, and Tybalt is now his brother-in-law, something that Tybalt is unaware of. As a results, Tybalt is hell-bent on fighting Romeo to regain his honour, which he considers to have lost when letting Romeo attend the Capulet Banquet. The audience is given the impression here that Tybalt is a stubborn and hot-headed character, while Romeo is calm, collected and more emotionally stable than Tybalt. * This builds tension as the characters get more and more agitated and more closer to fighting. Tension is also created as the audience is aware of the consequences the characters will face if they brawl once more. These consequences plague the minds of the audience who themselves become even more agitated and tense as the tension builds in the scene, which climaxes with the death of (L)Mercutio, which is swiftly followed by Tybalts own death. * Romeo makes a realisation that Juliets love has made him soft, and has prevented him from being a man and retaining his honour. Here, Shakespeare again highlights the irrational beliefs of upper-class men, but also, he may also be sending a message that it is important to love moderately and control your emotions and passions, as it can distract you from the realities of life, and eventually cause the love to die out prematurely. * Mercutio curses the two houses, both Capulet AND Montague, calling for a plague on both your houses. The plague of which Mercutio speaks of refers to the black plague that was rife in most parts of the world at the time. This plague is associated with death and devastation. This is the point at which the play turns for the worst. Before this scene, and this point in the scene, the play was heading towards a happy outcome, with Romeo and Juliet marrying in an effort to join the two families. After this point, Mercutio and Tybalt are killed, and Romeo exiled. It could be said that this curse foreshadows the rest of the play and inevitably leads to the end outcome of the play, with both Romeo and Juliet taking their lives. * Conclusion This scene is vital, as it is the climax of the whole play, and is the point at which the play turns for the worst. This scene creates a feeling of pity and fear within the audience, which is the main purpose of a tragedy play and flips the whole play around, and converts the atmosphere from one of peace and love to one of hate, violence and bloodshed. Shakespeare also points out many of the flaws of Society in this scene, and communicates with the audience, showing them that the beliefs of male dominance and the attitudes of the upper-class must be eradicated to create a peaceful, happier society.

Friday, April 10, 2020

Alternative chemical names Essay Example

Alternative chemical names Essay Example Alternative chemical names Essay Alternative chemical names Essay 1. Introduction: 1.1. Background on GHB Gamma hydroxybutyrate ( GHB ) is a fatty acid consists of a short concatenation with four Cs has the undermentioned expression: Ohio? ? ? CH2? ? ? CH2? ? ? ? CH2? ? ? ? COOH GHB has alternate chemical names including 4- hydroxybutyrate, 4- hydroxybutanoic acid, hydroxybutyric acid and Na ox bate. It is often supplied as a white pulverization that is odorless with somewhat piquant gustatory sensation, sometimes in capsules and on juncture as tablets. It can be taken orally and can be dissolved in H2O ( Wills, 2005 ) . GHB is a metabolite of Gamma -amino butyric acid ( GABA ) . Its presence in the encephalon shows unequal distribution and it is of import to cognize that comparatively higher degrees of GHB are discovered in kidney, bosom and skeletal musculus ( Nelson et al, 1981 ) . The normal concentration of GHB in the human encephalon is two to three times higher in the basal ganglia than in the intellectual cerebral mantles ( Okun et al. , 2001 ) . Barbaccia et Al, 2005 proposes that the presence of GHB in mammals including worlds, together with the unequal distribution in the encephalon and the talk that synthesis and release of GHB are regulated procedures, indicates that GHB may move as neurotransmitter and/or neuromodulator. GHB is an of import compound, in three respects, in that it is present endogenously as gamma Hydroxybutyric acid, abused drug as illegal GHB and a curative drug as Gamma Hydroxybutyrate, Na salt ; or sodium ox bates ( Carter et al. , 2009 ) . These facets are discussed below: 1.2. GHB as a curative drug GHB was synthesized in 1960 to bring forth an parallel for the ubiquitous inhibitory encephalon neurotransmitter GABA that would traverse the blood-brain barrier. It s used as anesthetic drug for minor surgical processs, but now the usage of GHB as an anesthetic is diminishing, although it is still permitted in Germany for endovenous anesthesia ( Caputo et al. , 2009 ) . GHB was known as Na ox bate under the trade name Xyrem for the intervention of cataplexy associated with narcolepsy, and for the intervention of utmost daytime drowsiness with narcolepsy ( Fuller and Hornfeldt, 2003 ) . Narcolepsy is considered as a sleep upset that is characterised by disconnected dark clip slumber and daylight sleepiness, and can besides include cataplexy which is characterised as loss of musculus tone with integral consciousness. Surveies in narcolepsy illustrate that GHB was valuable in handling the daylight cataplexy and helped it handling confused sleep/wake rhythms of these patients. GHB dark doses were selected to cut down the figure of night-time waking ups and daytime cataplexy ; besides it can develop a good form in narcoleptic patients ( Carter et al. , 2009 ) . In add-on, GHB is under survey for insomnia associated with schizophrenic disorder. There is some presymptomatic verification of the public-service corporation of GABA? -receptor agonists such as GHB for such sleep upsets ( Balla et al. , 2009 ) . GHB was found to cut down intoxicant backdown marks and symptoms such as shudder, sudating, sickness, depression, and anxiousness ( Gallimberti et al, 1989 ) . Reports are increasing about the effectivity of GHB in advancing abstinence in alkies taking to the blessing of GHB in Italy and Austria for the intervention of alcohol addiction under the trade name Alcover ( Begh A ; egrave ; and Carpanini, 2000 ) . A new survey, verified that GHB was more valuable than Valium in handling intoxicant backdown syndrome. GHB reduced anxiousness, agitation and current depression more quickly than Valium and every bit expeditiously as clomethiazole. GHB was used at the dosage of 50-100 mg/kg separated to three or four day-to-day doses, and no terrible side effects were registered ( Caputo et al. , 2009 ) . GHB is a supposed neurotransmitter that was consumed by organic structure builders to increase the release of growing endocrine, besides sold as a wellness quinine water to dieters and individuals with insomnia. GHB was manufactured throughout the late eightiess in the USA and marketed as a dietetic addendum in 1990s ( Chin et al, 1992, Okun et al. , 2001 and Wong et Al, 2004 ) . 1.3 GHB as a drug of maltreatment Throughout the late of 1990s GHB had became a popular drug in nines known as club drug due to its widespread among persons while go toing cabarets, raves, and circuit parties ( Wong et al, 2004 ) . GHB is abused significantly as a day of the month colza drug and as drug-facilitated sexual assault due to its ataractic and hypnotic effects ( Schwartz et al. , 2000 and Halkitis et al. , 2007 ) . In malice of Food and Drug Administration prohibition, this substance is still used. More than 40 instances of GHB toxic condition are reported in California with farther instances in other provinces. The forecast for GHB toxic condition instances is non bad ; there are no accepted studies of long-run inauspicious effects or deceases, nor any cogent evidence for physiological dependence ( Chin et al, 1992 ) . 2. Pharmacology of GHB Roth and Giarman ( 1970 ) demonstrated that GHB is a of course happening substance in the encephalon of mammals and suggested its function as a neurotransmitter. As illustrated in figure 1, the primary precursor of GHB in the encephalon is GABA, which is transformed into succinic semialdehyde ( SSA ) through a GABA-transaminase and so transformed into GHB by a specific succinic semialdehyde reductase ( SSR ) . GHB can besides be retransformed into SSA by a GHB dehydrogenase, and so SSA can be transformed back to GABA. SSA can besides be changed by succinic semialdehyde dehydrogenase ( SSADH ) into succinic acid and so extra metabolized by the Krebs rhythm in chondriosome ( Caputo et al. , 2009 ) . GHB was revealed to heighten the activity of ventral tegmental country ( VTA ) dopaminergic nerve cells by the suppression of VTA GABAergic nerve cells and hence GHB enhances the release of Dopastat into the karyon accumbens ( NAc ) . The changing of NAc Dopastat degree is the cardinal action of many drugs of maltreatment, but most of them besides act on other sender systems besides. The other major mark is the glutamatergic system: improved glutamate transmittal is necessary to show drug-seeking, Restoration or sensitisation ; besides many drugs are exciting their ain receptor in the NAc ( Molnar et al, 2009 ) . 2.1. Pharmacokineticss of GHB GHB soaking up is rapid and the peak plasma concentrations following unwritten disposal are 30- 60 proceedingss. Unlike GABA, GHB easy crosses the blood-brain barrier, and the plasma half life of GHB is 20-30 min ( van Noorden et al. , 2009 ) . Although nutrient did non change riddance and urinary elimination of unchanged GHB, nutrient well affect the bioavailability of GHB by cut downing peak plasma concentration, lifting average time-to-peak concentration, and doing the country under the plasma concentration-time curve to be decreased, ( Borgen et al. , 2003 ) . Clearance is 14.0 milliliter min? ? kilogram? ? at a dosage of 12.5 mg/kg and half life is 20 proceedingss. GHB metamorphosis is really fast and leads it to come in the citric acerb rhythm as succinate which is converted to CO2 + H2O ( Doherty et al. , 1975 ) . GHB is about wholly oxidised to carbon dioxide and about 2- 5 % was eliminated in the piss ( Gantt et al. , 1997 ) . GHB is excreted in the piss, its about less than 5 % being unchanged with a maximal concentration after about 60 min. Therefore, GHB can non be detected after 24 hours following disposal, and piss can be used in forensic probes merely when the sample is collected about instantly after ingestion ( Brenneisen et al. , 2004 ) . GHB pharmacokinetics has been verified as nonlinear in worlds and rats and whole clearance diminutions with lifting dosage. Assorted mechanisms are joined to the nonlinear pharmacokinetics and these include capacity-limited metamorphosis, saturable soaking up, and nonlinear nephritic clearance. Nephritic clearance becomes increasingly of import in overdose conditions with high urinary concentrations reported in worlds ; nevertheless, metabolic clearance considered as the chief riddance tract for GHB ( Morris and Felmlee, 2009 ) . Elimination half-life corresponds to the clip needed for the concentration of drug in the plasma, or the drug sum in the organic structure, to cut down by half or 50 % , the t? of GHB is 0.3 -1.0 H, and the volume of distribution is 0.4 L/kg. Bioavailability of GHB after unwritten consumption is rather low, after five half-lives or about 97 % of a drug is eliminated from the organic structure ( Jones et al. , 2009 ) . 2.2. Pharmacodynamics of GHB GHB binds to both specific high-affinity GHB sites and to GABA? receptors, doing the apprehension of its neuropharmacology rather complex ( H A ; oslash ; g et Al, 2008 ) . Carter et al, 2009, revealed that there are several likely pharmacological mechanisms for GHB. GHB is metabolized to GABA, which binds to GABAA and GABA? receptors. Besides GHB can adhere to GABA? and/ or GHB receptors, like the NCS-382 ( 6, 7, 8, 9 -tetrahydro-5 ( H ) -5-ol- ylidene acetic acid ) drug besides adhering to GHB receptors. Selective ligands for GABAA, GABA? and GHB receptors are shown in Figure 2. A figure of the behavioural effects of GHB are non reversed by the GHB receptor adversary NCS-382, and are blocked by GABA? receptor adversaries. NCS-382 does non impact GABAA receptor-gated chloride channels or the GABA? receptor ( Ticku and Mehta, 2008 ) . This shows that some of the effects are independent of GHB receptors and GABA receptors. There is grounds from surveies of the interactions of GHB and baclofen with adversaries at the subtype of glutamate receptors called N-methyl-D-aspartate ( NMDA ) . The NMDA adversary dizocilpine ( MK- 801 ) increases GHB-induced catalepsy in gnawers and these cataleptic effects of GHB are increased non merely by MK-801 but besides by other drugs with NMDA antagonist action, such as PCP ( PCP ) and Ketalar, on the other manus, these NMDA adversaries do non impact the cataleptic effects of baclofen ( Koek et al, 2009 ) . The surveies show that chronic GHB usage enhances dopaminergic, acetylcholinergic and serotonergic neurotransmission, and down-regulation of GABA receptors ( van Noorden et Al, 2009 ) . 2.2.1. GABA receptors ( GABAA and GABA? receptors ) GABA? receptors are present on GABAergic and non-GABAergic nerve cells and can modulate neural ( GABAergic ) signalling pre- and post-synaptically by diminishing neurotransmitter release ( Bonanno and Raiteri, 1993 ) . Activation of GABA? receptors can increase the production of some neuroactive steroids that positively modulate GABAA receptors ( Barbaccia et al, 2002 ) . Activation of GABA? receptors by GHB can explicate the effects of GHB on GABAA receptor. Animal surveies revealed that GHB causes absence-like ictuss and this type of ictuss is aggravated by GABAA agonists ( Snead and Liu, 1992 ) . GHB effects differ from the effects of GABA, even though GHB is closely related to GABA and can trip GABA? receptors in elevated doses ( Molnar et al, 2009 ) . GHB is known to be metabolized to GABA and to adhere to GABAB and GHB receptors without demoing considerable binding to sites on GABAA receptors ( Carter et al, 2009 ) . GHB in little doses has anxiolytic effects in rats, these anxiolytic effects are non opposed by the GHB receptor adversary, NCS-382, nor by Narcan, which is the opioid receptor adversary. However, the anxiolytic effects of GHB are reversed by flumazenil, which is the benzodiazepine receptor adversary, bespeaking GHB interaction with GABAA receptors that mediate the anxiolytic effects of benzodiazepines ( Schmidt-Mutter et al. , 1998 ) . GHB given exogenously to cut down the symptoms of intoxicant backdown syndrome in worlds due to the transition of GHB to GABA which activate GABAA receptors ( caputo et al, 2009 ) . The chief important clinical consequence of exogenic GHB is a cardinal nervous system depression by adhering to the GABA? receptor. Surveies are show that GHB activates the GABA? receptor either straight or after transition into GABA ( Ticku and Mehta, 2008 ) . 2.2.2. Gamma-hydroxybutyrate ( GHB ) receptors GHB besides binds to the GHB receptors which are reported to be present in the mammalian encephalon. Several structural parallels of GHB were established to hold a selective activity for the GHB receptor without any consequence of GABA? receptor ( Ticku and Mehta, 2008 ) . Newly established derived functions of phenylacetic acid, including the nonsteroidal anti-inflammatory drug ( NSAID ) diclofenac, bind to definite GHB adhering sites with affinity similar to GHB, and the presence of these separate GHB binding sites is besides supported by the production of selective GHB ligands such as NCS-382 ( H A ; oslash ; g et al. , 2008 ) . GHB receptors are found chiefly in nerve cells of the cerebral mantle, striate body, and hippocampus. Not merely is GHB an endogenous substrate for GHB receptors but besides succinate, a common tricarboxylic acerb rhythm metabolite binds to the same site ( Molnar et al, 2009 ) . 2.3. GHB prodrugs: gamma-butyrolactone ( GBL ) and 1, 4-butanediol ( 1, 4-BD ) The GHB parallels GBL and 1, 4-BD became popular drugs, as a effect of the Food and Drug Administration prohibition on nonprescription GHB in 1990, they are quickly metabolized to GHB by the enzymes serum lactonase and intoxicant dehydrogenase, respectively.The clinical effects of GBL and 1, 4-BD are tantamount to the effects of exogenously administered GHB e.g. , sleepiness, euphory and animal feeling ( van Noorden et Al, 2009 ) . GBL and 1, 4-BD compounds are present of course in rat encephalon at concentrations of about 1/10 of concentrations of GHB. These paths may be of significance to the synthesis of GHB under restricting conditions ( Lyon et al, 2007 ) . 3. Behavioral effects of GHB Survey in 1964 characterizes GHB as hypothermic, hypnotic, anesthetic, and anti-convulsant, with no clear respiratory depression or toxicity ( Carter et al, 2009 ) . Regular disposal of GHB causes down ordinance of GABA receptors, this lead to drug dependance as a agency to maintain up homeostasis ( Constantinides and Vincent, 2009 ) . A figure of carnal surveies indicate that the habit-forming belongingss of GHB may be mediated through the GABA? receptor ( van Noorden et Al, 2009 ) . Numerous surveies propose that GABA? receptors are chiefly indispensable for assorted behavioral effects of GHB, including hypolocomotion, catalepsy, ataxy, loss of compensating, decreased operant responding, and discriminatory stimulation effects. The typical GABA? receptor agonist baclofen besides produce all of these effects of GHB. GABA? receptors have a important function on the GHB effects ; nevertheless, the effects of GHB are like but non indistinguishable to the effects of the baclofen, which is a typical GABA? receptor agonist ( Koek et al, 2009 ) . 4. Changes in cistron look in GHB treated cells GHB is known to hold profound pharmacological effects, through binding to either the GHB receptor or GABA receptors. It is therefore possible that exposure to GHB can be monitored beyond 12 hours by mensurating GHB dependent alterations in cistron look. In old surveies, two messenger RNA transcripts have been identified as being up regulated following GHB exposure epiregulin and Phosphoprotein enriched in astrocytes of 15 kDa ( PEA-15 ) . The same survey revealed that GHB bring on cistron look alterations in a mouse theoretical account, and these alterations depend on the clip interval station exposure ( Larson et al, 2007 ) . 4.1. Epiregulin look in GHB treated cells The growing and distinction of cells are controlled by peptide growing factors and there is grounds that this growing control involves growing factors and their receptors in tumour every bit good as non-tumor cells. Epiregulin is considered as a member of the cuticular growing factor household ( Toyoda et al, 1995 ) . The cuticular growing factor receptor ( EGFR ) belongs to a household of cell surface receptor tyrosine kinases and many different growing factors can function as ligands for the EGFR and these include cuticular growing factor ( EGF ) , transforming growing factor-R ( TGF-R ) , heparin-binding EGF-like growing factor ( HB-EGF ) , betacellulin ( BTC ) , amphiregulin ( AR ) , epiregulin ( EPR ) , and epigen ( EPG ) . All EGFR ligands are synthesized as membrane proteins and released from the cell surface by regulated proteolysis ( Baldys et al, 2009 ) . 4.2. Phosphoprotein enriched in astrocytes of 15 kDa ( PEA-15 ) look PEA-15 is a little protein ( 15 kDa ) that was recognized ab initio as a plentiful phosphoprotein in encephalon astrocytes. A figure of surveies have established that PEA-15 regulate multiple cellular maps through its interaction with constituents of chief intra- cellular transduction tracts ( Sharif et al, 2004 ) . PEA-15 is a little anti-apoptotic protein expressed in a wide assortment of tissues and enrich in astrocytes, a figure of surveies showed that PEA-15 is capable to adhere to the extracellular signal-regulated kinase 2 ( ERK2 ) , even though it is non a substrate. The ERK2 cascade is activated by a aggregation of external factors such as growing factors, endocrines, and neurotransmitters. When initiated, the cascade plays of import functions in a scope of cellular actions such as proliferation, distinction, and programmed cell death. The inactivated ERK2 is normally situated in the cytosol. The over look of PEA-15 prevents ERK2 from roll uping in the karyon, proposing that one function of PEA-15 is to attach ERK2 in the cytosol ( Callaway et al, 2007 ) . PEA-15 plays an anti-apoptotic function in cellular tracts in a figure of cell types including malignant neoplastic disease cells and it s more expressed in terminally differentiated cells advancing endurance ( Mizrak et al, 2007 ) . Phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes ( PED/PEA-15 ) is overexpressed in several tissues of persons affected by type 2 diabetes. In integral cells and in transgenic animate being theoretical accounts, PED/PEA-15 over look impair insulin ordinance of glucose conveyance and this is mediated by its interaction with the C-terminal D4 sphere of phospholipase D1 ( PLD1 ) and the attendant addition of protein kinase C- activity. ( Viparelli et al, 2008 ) 4.1. SHSY5Y cell line The SH- SY5Y cell line is a three times cloned neuroblastoma cells, originated from the neuroblastoma line SK-N-SH which are originally established from a bone marrow biopsy of a neuroblastoma patient and neuroblastoma line SK-N-MC. SHSY5Y cells are described foremost in 1978 and go avaiable for surveies ( ( Biedler et al,1973 and Biedler et al,1978 ) . Recent surveies in SH-SY5Y cell lines illustrate the efficiency of transition of 1,4 Butanediol to GHB when the chief GHB synthesis tract from GABA is closed, one time the concentration of GHB is lowered, the cell respond to counterbalance GHB, this explains the presence of specific doorsill for GHB in the cell ( Lyon et al, 2007 ) . The SHSY5Y cells are often used as a neural cell theoretical account due to their sympathetic characteristic and low resting membrane potency, SHSY5Y cells are used in many surveies associating to tumour cell growing and neural cell biological science ( Tosetti et al, 1998 ) . Astroglial cell line The cardinal nervous system consists of a figure of cell populations, largely nerve cells, microglial cells and macroglial cells. The chief macroglial cell types are astrocytes and oligodendrocytes. Many maps including cellular support, ion homeostasis, neurotransmitters uptake, CNS immune system part and neuromodulation are attributed to astroglia ( Ridet et al, 1997 ) . Astrocytes are late considered as cells that propagate Ca2+ over drawn-out distance in response to stimulation, and, like nerve cells, release senders ( called gliotransmitters ) in a Ca2+-dependent mode to set a host of important encephalon maps. Astrocytes are besides stated to play an of import function in modulating neural excitant synaptic activity by Ca2+-dependent release of the gliotransmitters glutamate and ATP ( Fiacco, et Al, 2009 ) . Recent surveies found that the chief consequence of GHB in the karyon accumbens ( NAC ) was the activation of subpopulation of astrocytes. It induced Ca2+ transients in a subpopulation of astrocytes and this consequence is dose-dependent. GHB did non move on GABA? receptor or GHB receptor in the NAC, but induced Ca2+ transients in a subpopulation of astrocytes. The activation of astrocytes by GHB proposes their association in GHB-mediated physiological effects ( Molnar et al, 2009 ) . 5. Purpose of this survey This survey is aimed to widen the window of sensing of GHB beyond 12 hours through happening robust alternate markers of GHB disposal. GHB maltreatment and particularly in day of the month colza sexual assaults has increased in recent old ages. Current sensing methods rely on trying blood and piss but the rapid rate of metamorphosis of GHB means that GHB can vanish and the condemnable instances are frequently hard to prosecute. However, GHB is known to hold profound pharmacological effects, through binding to either the GHB receptor or GABA receptors. It is therefore possible that exposure to GHB can be monitored beyond 12 hours by mensurating the GHB dependant alterations in cistron look. 6. Survey program In this survey, the consequence of different doses and times of GHB exposure on the look of epiregulin, PEA-15 and other cistrons in SH-SY5Y cells and astroglial cells will be evaluated utilizing a combination of quantitative RT-PCR, Western smudges and proteomics ( 2D-gels ) . I hope that a full look profile will be obtained, and besides that the mechanism of ordinance can be elucidated, including finding of the function of GHB and GABA receptors in interceding these effects, by proving GHB, GBL1 and1, 4-BD, in add-on to GHB and GABA receptors antagonsts. 7. Decision GHB is an of import and actuating compound in that it is present endogenously as gamma Hydroxybutyric acid, abused drug as illegal GHB, and a curative drug as Gamma Hydroxybutyrate, Na salt ; or sodium ox bates. GHB has been extensively used in a date-rape sexual assaults in the last old ages and the condemnable instances are frequently hard to prosecute, it causes a forensic job due to its rapid metamorphosis and riddance. GHB is besides found endogenously as a metabolite of GABA neurotransmitter. However, it expresses many characters that indicate it can be a neurotransmitter itself. GHB is an of import and actuating compound in that it is present endogenously, abused drug, and a curative drug. 8. Mentions: Baldys A. , Go?oz M. , Morinelli TA. , Lee MH. , Raymond JR. , Luttrell LM. and Raymond Sr. ( 2009 ) . Essential function of c-Cbl in amphiregulin-Induced Recycling and signaling of the endogenous cuticular growing factor receptor. Biochemistry, Vol. 48, No.7: 1462-1473 Balla A. , Nattini M.E. , Sershen H. , Lajtha A. , Dunlop D.S. , and Javitt D.C. ( 2009 ) . 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Monday, March 9, 2020

What You Should Know About Econometrics

What You Should Know About Econometrics There are many ways to define econometrics, the simplest of which is that they are statistical methods used by economists to test hypotheses using real-world data. More specifically, it quantitatively analyzes economic phenomena in relation to current theories and observations in order to make concise assumptions about large data sets. Questions like Is the value of the Canadian dollar correlated to oil prices? or Does fiscal stimulus really boost the economy? can be answered by applying econometrics to datasets on Canadian dollars, oil prices, fiscal stimulus, and metrics of economic well-being. Monash University defines econometrics as a set of quantitative techniques that are useful for making economic decisions while The Economists Dictionary of Economics defines it as the setting up of mathematical models describing mathematical models describing economic relationships  (such as that the quantity demanded of a good is dependent positively on income and negatively on price), testing the validity of such hypotheses and estimating the parameters in order to obtain a measure of the strengths of the influences of the different independent variables. The Basic Tool of Econometrics: Multiple Linear Regression Model Econometricians use a variety of simple models in order to observe and find correlation within large data sets, but the most essential of these is the multiple linear regression model, which functionally predicts the value of the two dependent variables as a function of the independent variable. Visually, the multiple linear regression model can be viewed as a straight line through data points that represent paired values of the dependent and independent variables. In this, econometricians attempt to find estimators that are unbiased, efficient, and consistent in predicting the values represented by this function. Applied econometrics, then, uses these theoretical practices to observe real-world data and formulate new economic theories, forecast future economic trends, and develop new econometric models which establish a basis for estimating future economic events as they relate to the data set observed. Using Econometric Modeling to Evaluate Data In tandem with the multiple linear regression model, econometricians use a variety of econometric models to study, observe, and form concise observations of large data sets. The â€Å"Economics Glossary† defines an econometric model as one â€Å"formulated so that its parameters can be estimated if one makes the assumption that the model is correct.† Basically, econometric models are observational models that allow for quickly estimating future economic trends based on current estimators and exploratory data analysis. Econometricians often use these models to analyze systems of equations and inequalities such as the theory of supply and demand equilibrium or predicting how a market will change based off of economic factors like the actual value of domestic money or the sales tax on that particular good or service. However, since econometricians cannot typically use controlled experiments, their natural experiments with data sets lead to a variety of observational data issues including variable bias and poor causal analysis that leads to misrepresenting correlations between dependent and independent variables.

Saturday, February 22, 2020

The Competitiveness of the US Economy Essay Example | Topics and Well Written Essays - 500 words

The Competitiveness of the US Economy - Essay Example For the past 15 years, the nation has maintained its position as the most competitive economy in the world amidst the challenges in the rapidly evolving global environment. During 2007, the IMD World Competitiveness Yearbook together with the World Economic Forum cited that US is "arguably the country with the most productive and innovative potential in the world" (Reuters 2007). Amidst this regard for US competitiveness, this paper argues that the economy should watch out and safeguard this status in the face of recession it is undergoing. A country's competitiveness is indicated not just by economic strength but through the creation of a market environment which promotes healthy and unbiased competition among industry players. In order to be competitive, leaders should pursue policies which treat players equally. In an extreme case, competitiveness is indicated by a market where there is no government intervention (McConnell & Brue 2002). However, in the world today this system is not feasible and thus, competition is promoted through little or balanced intervention from the state. This paper believes that US economy is by far the most competitive economy in world noting the government's quest in promoting efficiency and fair play.