Kaposi’s Sarcoma: Insights into its Understanding

Kaposi’s Sarcoma: Insights into its Understanding Abstract Kaposi’s Sarcoma (KS) is a common vascular tumor arising in human immunodeficiency virus (HIV) infected patients and is one of the 27 conditions designated by the Centers for Disease Control as an acquired immunodeficiency syndrome (AIDS) defining illness. Human herpes virus-8 (HHV-8), now called Kaposi’s sarcoma-associated herpes virus (KSHV), is a member of ÃŽ ³ herpes virus family and is considered to be the causative agent of KS. This review aims to discuss KS and its association with HIV/AIDS with an emphasis on oral features, the role of HHV-8/KSHV in causation of KS, and the current challenges faced in management of the disease. Key words: acquired immunodeficiency syndrome, human herpes virus-8, Kaposi’s sarcoma, Kaposi’s sarcoma-associated herpes virus Introduction In 1869, Helmut Kobner, a German physician, appears to have been the first to describe cases of metastatic cutaneous sarcoma. In 1872, the Hungarian physician, Moricz Kaposi, described an idiopathic, multipigmented, tumor-like lesion of the skin that eventually was named Kaposi’s Sarcoma (KS).1,2 During the 19th century, KS was considered a rare disease and by the early 20th century, an increased incidence was suggested.2,3 KS is now a common vascular tumor arising in human immunodeficiency virus (HIV) infected patients, and is one of the 27 conditions designated by the Centers for Disease Control as an acquired immunodeficiency syndrome (AIDS) defining illness.2,4 Human herpes virus-8 (HHV-8), also called Kaposi’s sarcoma-associated herpes virus (KSHV), a member of ÃŽ ³ herpes virus family, is considered to be the causative agent of KS.5 Clinical Features Based on epidemiology and demographics, there are four variants of KS: 1) Classic KS that is relatively benign and predominantly occurs in elderly men of Mediterranean, Eastern European, or Middle Eastern descent with a median age of > 70 years; 2) an Endemic or â€Å"African† form of KS that also occurs predominantly in men at a ratio of 3:1 with a peak median age of 35 to 39 years; 3) Iatrogenic or Post-transplant KS that may occur in HIV-seronegative immunocompromised individuals, long term users of steroids and cytotoxic drugs, and individuals with autoimmune disorders; and 4) AIDS-associated KS. Although the four variants of KS are distinctive, they share similar clinical and histologic features, suggestive of common pathogenesis.5 In contrast to classic KS, which is often limited to the extremities, AIDS-associated KS frequently involves the muco-cutaneous regions of the head and neck as primary sites, and visceral involvement is also present.6 Muco-cutaneous lesions of the head and neck region, occur in estimated 10% of AIDS patients.7 The oral cavity is frequently involved with the hard and soft palate, gingiva, and tongue being the most common sites.8,9 The prevalence of oral KS varies from 0-12% in Africa, and from 0-38% in United States and Europe.10,11 A high prevalence of oral KS was demonstrated in 18.6% of a group of HIV-infected patients in Zimbabwe. Since the advent of AIDS, KS has become more frequent in both the genders, the male to female ratio changing from 19:1 to 7:1, particularly in East Africa.12 On the basis of clinical appearance, AIDS-associated KS is classified into six major overlapping types: patch, plaque, nodular, telangiectatic, infiltrative, and florid.1,3,13,14 Oral lesions appear as red to purple macules, papules, or nodules that may ulcerate and cause local destruction.9,15 Although the clinical behavior of AIDS-associated oral KS is rather unpredictable, majority of the cases represent aggressive disease and have associated disseminated cutaneous and visceral lesions.16 Slow growing oral tumors are generally associated with patients who have no additional complicating opportunistic infections.17 Differential Diagnosis Early lesions of KS may be difficult to distinguish from ecchymoses, nevi, dermatofibroma, and lichen planus.18 Nodular or plaque like lesions overlying mucosa should be biopsied to rule out bacillary angiomatosis, hemangioma, pyogenic granuloma, angiosarcoma, or lymphangiosarcoma.18,19 Histopathology The cellular origin of KS is difficult to determine as lesions typically exhibit multiple cell types. The tumor is mainly composed of undifferentiated mesenchymal cells and spindle-shaped cells.20-23 The spindle cells, considered the tumor element, are of mesenchymal origin and have features that resemble both endothelial and smooth muscle cells.22,23 The tumor cells may be derived from cells of either lymphatic or venous differentiation.17,22 Also, biopsies of KS feature numerous slit like vascular channels and may present extravasation of erythrocytes, hemosiderophages, eosinophilic hyaline inclusions, and inflammatory infiltrate.9,20,21 The histogenesis of the spindle cell component, believed to be the KS tumor cell, remains controversial; although many studies favor an endothelial cell origin.22-24 Another highly debatable issue is whether KS is a clonal â€Å"neoplastic† lesion, or whether it is â€Å"reactive† and polyclonal. Most of the evidence suggests that many KS lesions are hyperplastic and polyclonal in nature, but that either these lesions contain a small proportion of clonal, neoplastic tumor cells that are difficult to identify and culture, or some of these polyclonal lesions may undergo full transformation during disease progression, probably when an actively proliferating cell acquires genetic alterations that provide a selective advantage, leading to the emergence of a truly neoplastic clone in the minority of cases of KS.24 Role of HHV-8/KSHV HIV Multiple agents, including cytomegalo virus, hepatitis-B virus, human herpes virus-6, HIV, and Mycoplasma penetrans, have been suspected in the past as causing KS; but none of these have been clearly shown to present in most cases and to have a causal association with KS.24 Thus, although an infectious origin has long been suspected, it was only in 1994 that HHV-8/KSHV was first detected in KS specimens.25 KSHV is now considered the causative agent of AIDS-associated, classic, endemic, and iatrogenic KS. In addition, it is also believed to be the causative agent of primary effusion lymphomas (body cavity based lymphomas),26 multicentric Castlemans disease,26,27 and possibly oral plasmablastic lymphomas.28 Serological studies have indicated that unlike other human herpes viruses, KSHV is not ubiquitous.26 The seroprevalence of KSHV is low in the United States and parts of Europe (ranging from 0 to 20%), rising in Mediterranean countries to reach levels greater than 50% in some geographic regions of Africa.12 In North America and Europe, primary infection with KSHV mainly occurs among adult homosexual men and is transmitted principally via sexual contact; the KSHV seroprevalence being associated with the number of sexual partners and sexual practices.12,26 Transmission of KSHV via saliva has also been documented.29 In African populations, KSHV infection seems to occur largely before puberty through casual family and community contacts; oral secretions being a potential vehicle of non-sexual horizontal spread; vertical transmission of KSHV being insignificant.12,26 A recent study conducted in Malawi, Africa, has also shown that, apparently, healthy people in regions where KSHV is endemic can be infected by multiple strains.30 However, it is still unclear if this reflects a simultaneous co-infection by several KSHV strains, reactivation of latent strains, or super infection.30 KSHV is lymphotropic and is more closely related to Epstein-Barr virus and herpes virus saimiri than to other herpes viruses.5,27 The KSHV genome contains several genes related to cellular genes involved in cell proliferation and host responses that probably contribute to viral pathogenesis.26,31 The pathogenesis of AIDS-associated KS is multifactorial and involves KSHV, altered expression and response to cytokines, and stimulation of KS growth by HIV trans-activation protein (tat).32,33 KSHV is a necessary, but solely not a sufficient cause of KS.34 It encodes protein homologues of interleukin-6, chemokines of the macrophage inflammatory protein family, cell cycle regulators of the cyclin family, and anti-apoptotic genes of the bcl-2 family.26 The HIV tat protein can promote the growth of spindle cells of endothelial origin, but only in presence of inflammatory cytokines.32,33 The synergistic relationship between inflammatory cytokines and HIV tat protein, when combined with the immunosuppression associated with AIDS, may provide an explanation for aggressive nature of AIDS-associated KS compared to relatively non-aggressive, classic Mediterranean form in which the HIV tat protein does not play a role.33 The sequence of events creating the inflammatory angiogenic environment has been described by Dezube 33 as follows: 1) circulating KS progenitor cells and cells latently infected with KSHV seek sites of pre-existing inflammation; in the case of oral KS, pre-existing inflammation may include acute and/or chronic periodontal disease sites; 2) exposure to inflammatory cytokines such as interferon-ÃŽ ± (IFN-ÃŽ ±) results in differentiation of latently infected cells into KS-like spindle cells and induces KSHV reactivation; 3) reactivation of KSHV leads to expression of potentially pathogenic genes such as viral interleukin-6 that in turn, can activate vascular endothelial growth factor and induce angiogenesis; 4) viral lytic replication in the same cells activates inflammation, which also may play a role in angiogenesis; 5) the creation of inflammatory-angiogenic environment increases the availability of infectable cells, i.e. endothelial and KS spindle cells, which are then included in the development of the lesion; 6) cells also become responsive to HIV tat protein; and 7) the HIV tat protein augments the inflammatory-angiogenic state by the increasing angiogenic activities of basic fibroblast growth factor, IFN-ÃŽ ±, and vascular endothelial growth factor by mimicking the effects of the external matrix proteins fibronectin and vitronectin and by increasing the expression of matrix metalloproteinases. Prognosis and Management The prognosis of patients with AIDS-associated KS is often related to factors other than the tumor burden itself. In 1989, the AIDS trial council group devised the TIS staging system, based upon the extent of tumor (T), the status of immune system in terms of CD4+ T-cell count (I), and the presence of other systemic HIV-related illness (S).12 At present there is no treatment for AIDS-associated KS. Treatment is thus directed towards the elimination, or at least reduction of cosmetically unacceptable lesions, pain, and edema, as well as the relief of symptoms caused by visceral involvement.33 Local therapy may be effective for limited disease, but systemic therapy is required for disseminated KS.33 Highly active anti-retroviral therapy (HAART) is useful in the management of AIDS-associated KS, as it will reduce the HIV viral load and raise the CD4+ T-cell count, both of which contribute to the pathogenesis of KS. Recent reports have described a reduced incidence or regression of KS in HIV-infected individuals treated with HAART that includes at least one protease inhibitor. Both in vivo and in vitro studies have demonstrated that protease inhibitors have a direct anti-angiogenic, anti-KS, and anti tumor activity at concentrations likely to be present in the blood of treated individuals. HAART causes fall in KSHV levels in the blood presumably because of a reduction in HIV proliferation, HIV/KSHV-mediated oncogenesis, and HIV-induced immunosuppresion.12 Older approaches of managing oral KS have included local irradiation, intralesional injections of vinblastine and 3% sodium tetradecyl sulphate, laser therapy, surgical excision, cytotoxic therapy with vinca alkaloids (vinblastine, vincristine, and vinorelbine), bleomycin, anthracyclines, paclitaxel, and liposomal anthracyclines. However, only five agents are commonly used for the treatment of KS: alitretinoin gel for topical therapy, and liposomal daunorubicin and oloxorubicin, paclitaxel, and IFN-ÃŽ ± for systemic therapy.12 The strong angiogenic component of KS makes it particularly suitable for treatment with drugs that act as anti-angiogenic agents such as thalidomide and newer agents such as matrix metalloproteinases and IM-862. Based upon the apoptotic and anti-proliferative activity of iron chelation on KS cells, it is also suggested that withdrawal strategies may be effective. Several retinoid compounds have also been tested in clinical trials for KS, with a response rate of 23-37%.12 Direct antiviral approaches targeting KSHV have been proposed. In vitro studies have shown that KSHV is very sensitive to cidofovir, moderately sensitive to ganciclovir and foscarnet, but only weakly sensitive to acyclovir. However, the efficacy of cidofovir in vivo has yet to be proven. IFN-ÃŽ ± may inhibit infection or reactivation by KSHV. Single agent therapy with IFN-ÃŽ ±, is associated with significant toxicity, but when in combination with anti retroviral agents it may have some application for disseminated, but non-rapidly progressive KS.12 Conclusions Studies pertaining to KS suggest epidemiologic patterns that are consistent with a sexually transmitted agent, before a viral agent HHV-8/KSHV was identified, and that it is strictly not an opportunistic infectious agent related to HIV/AIDS-associated KS. Immune suppression along with genetic and/or environmental factors may interplay in variable combinations in the eventual causation of KS. Currently, a wide array of treatment modalities for KS, are aimed at elimination of cosmetically unacceptable lesions, reduction of unsightly edema and lymphadenopathy, and to alleviate symptoms caused by systemic involvement.

Literary Genre Essay

Literature (from Latin litteraetantri (plural); letter) is the art of written works, and is not bound to published sources (although, under circumstances unpublished sources can be exempt). Literally translated, the word literature means â€Å"acquaintance with letters† (as in the â€Å"arts and letters†). The two major classification of literature are poetry and prose. â€Å"Literature† is sometimes differentiated from popular and ephemeral classes of writing. Terms such as â€Å"literary fiction† and â€Å"literary merit† are used to distinguish individual works as art-literature rather than vernacular writing, and some critics exclude works from being â€Å"literary†, for example, on grounds of weak or faulty style, use of slang, poor characterization and shallow or contrived construction. Others exclude all genres such as romance, crime and mystery, science fiction, horror and fantasy. Pop lyrics, which are not technically a written medium at all, have also been drawn into this controversy. POETRY A poem is a composition written in verse (although verse has been equally used for epic and dramatic fiction). Poems rely heavily on imagery, precise word choice, and metaphor; they may take the form of measures consisting of patterns of stresses (metric feet) or of patterns of different-length syllables (as in classical prosody); and they may or may not utilize rhyme. Relaxation Through Poetry is a tool used to help someone relax in times of stress. One cannot readily characterize poetry precisely. Typically though, poetry as a form of literature makes some significant use of the formal properties of the words it uses – the properties of the written or spoken form of the words, independent of their meaning. Meter depends on syllables and on rhythms of speech; rhyme and alliteration depend on the sounds of words. Arguably, poetry pre-dates other forms of literature. Early examples include the Sumerian Epic of Gilgamesh (dated from around 2700 B. C. ), parts of the Bible, the surviving works of Homer (the Iliad and the Odyssey), and the Indian epics Ramayana and Mahabharata. In cultures based primarily on oral traditions the formal characteristics of poetry often have a mnemonic function, and important texts: legal, genealogical or moral, for example, may appear first in verse form. Some poetry uses specific forms. Examples include the haiku, the limerick, and the sonnet. A traditional haiku written in Japanese relate to nature, contain seventeen onji (syllables), distributed over three lines in groups of five, seven, and five, and should also have a kigo, a specific word indicating a season. A limerick has five lines, with a rhyme scheme of AABBA, and line lengths of 3,3,2,2,3 stressed syllables. It traditionally has a less reverent attitude towards nature. Poetry not adhering to a formal poetic structure is called â€Å"free verse† Language and tradition dictate some poetic norms: Persian poetry always rhymes, Greek poetry rarely rhymes, Italian or French poetry often does, English and German poetry can go either way. Perhaps the most paradigmatic style of English poetry, blank verse, as exemplified in works by Shakespeare and Milton, consists of unrhymed iambic pentameters. Some languages prefer longer lines; some shorter ones. Some of these conventions result from the ease of fitting a specific language’s vocabulary and grammar into certain structures, rather than into others; for example, some languages contain more rhyming words than others, or typically have longer words. Other structural conventions come about as the result of historical accidents, where many speakers of a language associate good poetry with a verse form preferred by a particular skilled or popular poet. Works for theatre (see below) traditionally took verse form. This has now become rare outside opera and musicals, although many would argue that the language of drama remains intrinsically poetic. In recent years, digital poetry has arisen that takes advantage of the artistic, publishing, and synthetic qualities of digital media. An essay consists of a discussion of a topic from an author’s personal point of view, exemplified by works by Michel de Montaigne or by Charles Lamb. ‘Essay’ in English derives from ‘attempt. ‘ Thus, one can find open-ended, provocative and/or inconclusive essays. The term â€Å"essays† first applied to the self-reflective musings of Michel de Montaigne–even today he has a reputation as the father of this literary form. Genres related to the essay may include: †¢the memoir, telling the story of an author’s life from the author’s personal point of view †¢the epistle: usually a formal, didactic, or elegant letter. †¢works by Lady Murasaki[citation needed], the Arabic Hayy ibn Yaqdhan by Ibn Tufail, the Arabic Theologus Autodidactus by Ibn al-Nafis, and the Chinese Romance of the Three Kingdoms by Luo Guanzhong[citation needed]. Early novels in Europe did not count as significant litera perhaps because â€Å"mere† prose writing seemed easy and unimportant. It has become clear, however, that prose writing can provide aesthetic pleasure without adhering to poetic forms. Additionally, the freedom authors gain in not having to concern themselves with verse structure translates often into a more complex plot or into one richer in precise detail than one typically finds even in narrative poetry. This freedom also allows an author to experiment with many different literary and presentation styles—including poetry—in the scope of a single novel. Other prose literature Philosophical, historical, journalistic, legal and scientific writings are traditionally ranked as literature. They offer some of the oldest prose writings in existence; novels and prose stories earned the names â€Å"fiction† to distinguish them from factual writing or nonfiction, which writers historically have crafted in prose. Natural science As advances and specialization have made new scientific research inaccessible to most audiences, the â€Å"literary† nature of science writing has become less pronounced over the last two centuries. Now, science appears mostly in journals. Scientific works of Aristotle, Copernicus, and Newton still possess great value, but since the science in them has largely become outdated, they no longer serve for scientific instruction. Yet, they remain too technical to sit well in most programmes of literary study. Outside of â€Å"history of science† programmes, students rarely read such works. Philosophy Philosophy, too, has become an increasingly academic discipline. More of its practitioners lament this situation than occurs with the sciences; nonetheless most new philosophical work appears in academic journals. Major philosophers through history—Plato, Aristotle, Augustine, Descartes, Kierkegaard, Nietzsche—have become as canonical as any writers. Some recent philosophy works are argued to merit the title â€Å"literature†, such as some of the works by Simon Blackburn; but much of it does not, and some areas, such as logic, have become extremely technical to a degree similar to that of mathematics. History A great deal of historical writing ranks as literature, particularly the genre known as creative nonfiction. So can a great deal of journalism, such as literary journalism. However these areas have become extremely large, and often have a primarily utilitarian purpose: to record data or convey immediate information. As a result the writing in these fields often lacks a literary quality, although it often and in its better moments has that quality. Major â€Å"literary† historians include Herodotus, Thucydides and Procopius, all of whom count as canonical literary figures. Law Law offers a less clear case. Some writings of Plato and Aristotle, or even the early parts of the Bible, might count as legal literature. The law tables of Hammurabi of Babylon might count. Roman civil law as codified in the Corpus Juris Civilis during the reign of Justinian I of the Byzantine Empire has a reputation as significant literature. The founding documents of many countries, including Constitutions and Law Codes, can count as literature; however, most legal writings rarely exhibit much literary merit, as they tend to be rather garrulous. Drama A play or drama offers another classical literary form that has continued to evolve over the years. It generally comprises chiefly dialogue between characters, and usually aims at dramatic / theatrical performance (see theatre) rather than at reading. During the 18th and 19th centuries, opera developed as a combination of poetry, drama, and music. Nearly all drama took verse form until comparatively recently. Shakespeare could be considered drama. Romeo and Juliet, for example, is a classic romantic drama generally accepted as literature. Greek drama exemplifies the earliest form of drama of which we have substantial knowledge. Tragedy, as a dramatic genre, developed as a performance associated with religious and civic festivals, typically enacting or developing upon well-known historical or mythological themes. Tragedies generally presented very serious themes. With the advent of newer technologies, scripts written for non-stage media have been added to this form. War of the Worlds (radio) in 1938 saw the advent of literature written for radio broadcast, and many works of Drama have been adapted for film or television. Conversely, television, film, and radio literature have been adapted to printed or electronic media. Oral literature The term oral literature refers not to written, but to oral traditions, which includes different types of epic, poetry and drama, folktales, ballads. However the use of this oxymoron is controversial and not generally accepted by the scientific community. Some prefer to avoid the etymological question using â€Å"oral narrative tradition†, â€Å"oral sacred tradition†, â€Å"oral poetry† or directly using epics or poetry (terms that no necessarily imply writing), others prefer to create neologisms as orature.

The Count or Monte Cristo

Monte Cristo is paying an older gentleman to act as Marquis Bartolomeo Calvacanti, father of Andrea Calvacanti. They are both receiving an allowance to act as Andrea Calvacanti. They are presented to one another. Monte Cristo also invites them to his dinner party. He intends to introduce Andrea Calvacanti to Parisien society. Analysis: Monte Cristo is here setting the stage for Calvacanti's entrance to Parisien society where he will be instrumental in the downfall of Villefort, Caderousse, and Danglars. Chapter 32 In this chapter one learns that Maximilien Morrel and Valentine are in love.Valentine's father however, is to marry her off to Franz d'Epinay, whom she can never love. Her stepmother is opposed to the idea of her marrying in general for it means that Madame de Villefort's son will have nothing to inherit, for valentine will receive the fortune. Valentine and Maximilien meet in the garden, but Valentine must hurry off to meet her stepmother. Analysis: This chapter presents V alentine's marriage dilemma. Her father still is trying to loose his ties to the Bonapartists. He thus wishes to marry her to the son of a staunch royalist.Valentine, however, is closer to her Bonapartist grandfather. Noirtier will reveal his biggest secret to save her from the arms of a man she does not love. This chapter also presents Valentine's stepmother as a greedy mother who only seeks funds for her son. This woman's monetary greed foreshadows the tragedies that will strike the Villefort household. She is in fact a mirror image of Villefort, who was willing to sacrifice human life for is own gain. Chapter 33 Monsieur and Madame de Villefort live with Noirtier, Villefort's aged paralyzed father.Noirtier's fortune shall pass to Valentine upon her marriage. Thus, in this chapter, the Villefort's proceed to Noirtier's chamber to tell him of Valentine's coming marriage to Baron Franz d'Epinay. Noirtier is unable to speak since he suffered a stroke, however his discomfort and fury at this arrangement is apparent. There is existed much political enmity between Noirtier and this family. In fact, Noirtier was suspected of murdering the Baron's father. Villefort's goal in marrying Valentine to the Baron is thus to allay suspicion of this assassination. Valentine is summoned.She alone can decipher the old man's thoughts. He decides to make a will disinheriting Valentine if she marries the Baron. She, of course, approves of this for she does not wish to marry the Baron. She will still have Noirtier's love. Valentine also has other sources of income. Thus, Noirtier's actions are a threat to Villefort, not Valentine. Villefort, however, will not allow themselves to be intimidated by the whims of an old man. Let him donate his money to charity, says Madame de Villefort, for he has also made it clear that the money will not go to Madame de Villefort's son.Analysis: This chapter is a continuation of the previous chapter. Noirtier attempts to save Valentine from marriage . By denying her of his fortune, (but not his love) he hopes to prevent her father from marrying her to Franz. He will have to resort to greater measures, however. Only after he reveals his guilt in the death of Franz d'Epinay's father Chapter 34 The Count visits the Villeforts to remind them to attend his dinner party at his Auteuil house. Monsieur de Villefort of course recognizes the address of this haunting house.It is the one where he was stabbed attempting to bury his live newborn child. The Count also sends a telegram to Debray in this chapter relating a contrived news bulletin of a political chaos in Spain. Debray thus rushes to Danglars' wife telling her to recommend to her husband that he sell all his Spanish bonds. He does so, though he loses money. At the end of the day when the news is proven false, the bonds rise to twice their original value. The net loss for Danglars is thus a million francs. Analysis: The Count's mechanism to destroy two of his enemies is set in mot ion.He insists that the Villeforts attend, even though this shall be very emotionally taxing for the public prosecutor. The Count also is responsible for providing false information to Debray. This will cause Danglars to speculate incorrectly and lose one million francs. Chapter 35 The guests arrive at the dinner party. Monte Cristo serves them astounding exotic foods. Bertuccio, his servant recognizes Andrea Calvacanti as the newborn baby he has saved from Villefort's box. It is the baby his sister in law raised. He also recognizes Madame Danglars as the woman Villefort used to visit at Auteuil.After dinner, Monte Cristo gives the guests a tour of the house and makes several insinuations that a crime was committed in his new house. He gives the guest a tour, finally leading them to the garden where he says he dug up the skeleton of a newborn baby. All the while he has observed Villefort and Madame Danglars tremble. Analysis: The Count's tour causes Villefort and Madame Danglars muc h psychological trauma. The rest of the guest's are astounded at the Count's exotic hospitality. The exotic foods are a symbol of the Count's worldliness. He is no longer a naà ¯ve youth.Villefort trembles because he now realizes that the Count knows the secrets of his past. He is aware that there was no skeleton buried in the garden, for he had searched for this very same skeleton and had never found it. Thus, he is aware that the count is lying to everyone by saying that he had found the remains of a newborn baby. Chapter 36 Caderousse returns as an escaped convict and enters Andrea Calvacanti's carriage as he is leaving Monte Cristo's dinner party. He demands a cut of what Calvacanti is being paid by Monte Cristo. Andrea agrees. Analysis:This chapter links both Caderousse and Calvacanti (Benedetto). It creates tension between the two that shall not be resolved until Benedetto kills Caderousse when he attempts to rob the Count. Chapter 37 Monsieur Debray, upon leaving Monte Crist o's dinner party, returns to Madame Danglars' residence. He notices her agitation but she denies any trouble. Danglars enters their suite. He advises his wife that she should not keep Debray away from his house late at night since Debray's residence is some distance away. Debray is shocked at this intrusion.Danglars, however, wins the battle of words between himself and his wife. Debray leaves. Danglars proceeds to blame her for ruining his fortune. He demands that she pay him a quarter of what he lost because it was at her request that he had sold his Spanish bonds. After all, he reasons, when he earns money he pays her a cut of the profits. When he gives her this money he claims that he does not ask her where she spends it, though he insinuates that he knows she passes it on to Debray. Thus, if she does not have the money to pay for the loss, she should ask Debray for the money.Danglars knows all about her love affairs. He knows that Debray is not the first, and he tolerates it un til it dips into his fortune. He even knows that her past includes her lover Monsieur de Villefort, and that she was at one time six months pregnant by him. Madame Danglars is overwhelmed. Analysis: Monte Cristo has succeeded in ruining a million francs of Danglars' fortune by providing false knowledge to Debray. Danglars consequently falsely speculated after his wife relayed Debray's false information. Thus Monte Cristo is on the road to destroying the man who was the mastermind behind his incarceration.His destruction must occur slowly, however, just as he was made to rot slowly away in prison. Chapter 38 Danglars pays a visit to Monte Cristo. He complains of his investment adviser, Jacopo, who never made a mistake till now. He just lost seven hundred thousand francs at Trieste. Calvacanti is also opening credit with Danglars, and Monte Cristo backs up this man's â€Å"incredible fortune† verbally for Danglars. He also mentions that Calvacanti's son may be looking for a Par isien wife. Danglars, the speculator is intrigued at this prospect.He reveals to Monte Cristo that he is not completely sure about his daughter's engagement to Albert de Morcerf.. Danglars was made a baron, but de Morcerf made himself a count. They are both of humble birth, but there has been scandal attached to Morcerf's name. Monte Cristo feigns vague recollection of the Ali Pasha affair. Analysis: Monte Cristo continues to destroy Danglars financially. He also wishes to humiliate Danglars publicly. He thus introduces Danglars to the idea that Calvacanti may be looking for a Parisien wife such as Eugenie.Danglars shall make the arrangements for the betrothal despite his daughter's wishes. Chapter 39 Madame Danglars visits Monsieur de Villefort, for he had given her an appointment to discuss the previous evening's events. Recollect that Monte Cristo had told his guests that he had found a skeleton in the backyard of a newborn baby. However, Villefort now admits to Madame Danglars t hat this is impossible. It is impossible because he had returned after his recuperation from the Corsican's stabbing to find the garden devoid of any box containing the dead child.He thus assumes that the Corsican saved the child and that it is alive. Monte Cristo must know their secret and he swears to find out how. Within a week he says he will know who Monte Cristo really is, where he comes from, and why he knows their secret. Analysis: This chapter clarifies that Madame Danglars did not know that her baby was born alive. She believed it to be a stillbirth. She was unaware of Villefort's evil sin. Ironically, Villefort will soon know Monte Cristos true identity, but only once he has been ruined and Monte Cristo chooses to deliver the final blow.Chapter 40 Albert returns from Treport and visits Monte Cristo. Albert states that the thought of living with Mademoiselle Danglars every day horrifies him. Monte Cristo reassures Albert by stating that Monsieur Danglars may back out on hi s word in favor of another husband for his daughter. At this Albert wonders why he is not good enough for Danglars, despite his desire to be rid of the duty to marry. Monte Cristo reassures Albert Danglars is a man of bad taste, and thus prefers another to Albert. The Count or Monte Cristo Monte Cristo is paying an older gentleman to act as Marquis Bartolomeo Calvacanti, father of Andrea Calvacanti. They are both receiving an allowance to act as Andrea Calvacanti. They are presented to one another. Monte Cristo also invites them to his dinner party. He intends to introduce Andrea Calvacanti to Parisien society. Analysis: Monte Cristo is here setting the stage for Calvacanti's entrance to Parisien society where he will be instrumental in the downfall of Villefort, Caderousse, and Danglars. Chapter 32 In this chapter one learns that Maximilien Morrel and Valentine are in love.Valentine's father however, is to marry her off to Franz d'Epinay, whom she can never love. Her stepmother is opposed to the idea of her marrying in general for it means that Madame de Villefort's son will have nothing to inherit, for valentine will receive the fortune. Valentine and Maximilien meet in the garden, but Valentine must hurry off to meet her stepmother. Analysis: This chapter presents V alentine's marriage dilemma. Her father still is trying to loose his ties to the Bonapartists. He thus wishes to marry her to the son of a staunch royalist.Valentine, however, is closer to her Bonapartist grandfather. Noirtier will reveal his biggest secret to save her from the arms of a man she does not love. This chapter also presents Valentine's stepmother as a greedy mother who only seeks funds for her son. This woman's monetary greed foreshadows the tragedies that will strike the Villefort household. She is in fact a mirror image of Villefort, who was willing to sacrifice human life for is own gain. Chapter 33 Monsieur and Madame de Villefort live with Noirtier, Villefort's aged paralyzed father.Noirtier's fortune shall pass to Valentine upon her marriage. Thus, in this chapter, the Villefort's proceed to Noirtier's chamber to tell him of Valentine's coming marriage to Baron Franz d'Epinay. Noirtier is unable to speak since he suffered a stroke, however his discomfort and fury at this arrangement is apparent. There is existed much political enmity between Noirtier and this family. In fact, Noirtier was suspected of murdering the Baron's father. Villefort's goal in marrying Valentine to the Baron is thus to allay suspicion of this assassination. Valentine is summoned.She alone can decipher the old man's thoughts. He decides to make a will disinheriting Valentine if she marries the Baron. She, of course, approves of this for she does not wish to marry the Baron. She will still have Noirtier's love. Valentine also has other sources of income. Thus, Noirtier's actions are a threat to Villefort, not Valentine. Villefort, however, will not allow themselves to be intimidated by the whims of an old man. Let him donate his money to charity, says Madame de Villefort, for he has also made it clear that the money will not go to Madame de Villefort's son.Analysis: This chapter is a continuation of the previous chapter. Noirtier attempts to save Valentine from marriage . By denying her of his fortune, (but not his love) he hopes to prevent her father from marrying her to Franz. He will have to resort to greater measures, however. Only after he reveals his guilt in the death of Franz d'Epinay's father Chapter 34 The Count visits the Villeforts to remind them to attend his dinner party at his Auteuil house. Monsieur de Villefort of course recognizes the address of this haunting house.It is the one where he was stabbed attempting to bury his live newborn child. The Count also sends a telegram to Debray in this chapter relating a contrived news bulletin of a political chaos in Spain. Debray thus rushes to Danglars' wife telling her to recommend to her husband that he sell all his Spanish bonds. He does so, though he loses money. At the end of the day when the news is proven false, the bonds rise to twice their original value. The net loss for Danglars is thus a million francs. Analysis: The Count's mechanism to destroy two of his enemies is set in mot ion.He insists that the Villeforts attend, even though this shall be very emotionally taxing for the public prosecutor. The Count also is responsible for providing false information to Debray. This will cause Danglars to speculate incorrectly and lose one million francs. Chapter 35 The guests arrive at the dinner party. Monte Cristo serves them astounding exotic foods. Bertuccio, his servant recognizes Andrea Calvacanti as the newborn baby he has saved from Villefort's box. It is the baby his sister in law raised. He also recognizes Madame Danglars as the woman Villefort used to visit at Auteuil.After dinner, Monte Cristo gives the guests a tour of the house and makes several insinuations that a crime was committed in his new house. He gives the guest a tour, finally leading them to the garden where he says he dug up the skeleton of a newborn baby. All the while he has observed Villefort and Madame Danglars tremble. Analysis: The Count's tour causes Villefort and Madame Danglars muc h psychological trauma. The rest of the guest's are astounded at the Count's exotic hospitality. The exotic foods are a symbol of the Count's worldliness. He is no longer a naive youth.Villefort trembles because he now realizes that the Count knows the secrets of his past. He is aware that there was no skeleton buried in the garden, for he had searched for this very same skeleton and had never found it. Thus, he is aware that the count is lying to everyone by saying that he had found the remains of a newborn baby. Chapter 36 Caderousse returns as an escaped convict and enters Andrea Calvacanti's carriage as he is leaving Monte Cristo's dinner party. He demands a cut of what Calvacanti is being paid by Monte Cristo. Andrea agrees. Analysis:This chapter links both Caderousse and Calvacanti (Benedetto). It creates tension between the two that shall not be resolved until Benedetto kills Caderousse when he attempts to rob the Count. Chapter 37 Monsieur Debray, upon leaving Monte Cristo's dinner party, returns to Madame Danglars' residence. He notices her agitation but she denies any trouble. Danglars enters their suite. He advises his wife that she should not keep Debray away from his house late at night since Debray's residence is some distance away. Debray is shocked at this intrusion.Danglars, however, wins the battle of words between himself and his wife. Debray leaves. Danglars proceeds to blame her for ruining his fortune. He demands that she pay him a quarter of what he lost because it was at her request that he had sold his Spanish bonds. After all, he reasons, when he earns money he pays her a cut of the profits. When he gives her this money he claims that he does not ask her where she spends it, though he insinuates that he knows she passes it on to Debray. Thus, if she does not have the money to pay for the loss, she should ask Debray for the money.Danglars knows all about her love affairs. He knows that Debray is not the first, and he tolerates it until it dips into his fortune. He even knows that her past includes her lover Monsieur de Villefort, and that she was at one time six months pregnant by him. Madame Danglars is overwhelmed. Analysis: Monte Cristo has succeeded in ruining a million francs of Danglars' fortune by providing false knowledge to Debray. Danglars consequently falsely speculated after his wife relayed Debray's false information. Thus Monte Cristo is on the road to destroying the man who was the mastermind behind his incarceration.His destruction must occur slowly, however, just as he was made to rot slowly away in prison. Chapter 38 Danglars pays a visit to Monte Cristo. He complains of his investment adviser, Jacopo, who never made a mistake till now. He just lost seven hundred thousand francs at Trieste. Calvacanti is also opening credit with Danglars, and Monte Cristo backs up this man's â€Å"incredible fortune† verbally for Danglars. He also mentions that Calvacanti's son may be looking for a Parisi en wife. Danglars, the speculator is intrigued at this prospect.He reveals to Monte Cristo that he is not completely sure about his daughter's engagement to Albert de Morcerf.. Danglars was made a baron, but de Morcerf made himself a count. They are both of humble birth, but there has been scandal attached to Morcerf's name. Monte Cristo feigns vague recollection of the Ali Pasha affair. Analysis: Monte Cristo continues to destroy Danglars financially. He also wishes to humiliate Danglars publicly. He thus introduces Danglars to the idea that Calvacanti may be looking for a Parisien wife such as Eugenie.Danglars shall make the arrangements for the betrothal despite his daughter's wishes. Chapter 39 Madame Danglars visits Monsieur de Villefort, for he had given her an appointment to discuss the previous evening's events. Recollect that Monte Cristo had told his guests that he had found a skeleton in the backyard of a newborn baby. However, Villefort now admits to Madame Danglars that this is impossible. It is impossible because he had returned after his recuperation from the Corsican's stabbing to find the garden devoid of any box containing the dead child.He thus assumes that the Corsican saved the child and that it is alive. Monte Cristo must know their secret and he swears to find out how. Within a week he says he will know who Monte Cristo really is, where he comes from, and why he knows their secret. Analysis: This chapter clarifies that Madame Danglars did not know that her baby was born alive. She believed it to be a stillbirth. She was unaware of Villefort's evil sin. Ironically, Villefort will soon know Monte Cristos true identity, but only once he has been ruined and Monte Cristo chooses to deliver the final blow.Chapter 40 Albert returns from Treport and visits Monte Cristo. Albert states that the thought of living with Mademoiselle Danglars every day horrifies him. Monte Cristo reassures Albert by stating that Monsieur Danglars may back out on his w ord in favor of another husband for his daughter. At this Albert wonders why he is not good enough for Danglars, despite his desire to be rid of the duty to marry. Monte Cristo reassures Albert Danglars is a man of bad taste, and thus prefers another to Albert.

Research Proposal Examples - 3454 Words

Kostas E. Sillignakis – www.sillignakis.com SAMPLE OF RESEARCH PROPOSAL: â€Å"Rural Tourism Development for the Prefecture of Lassithi in Crete.† 1.0 INTRODUCTION TO PROBLEM STATEMENT AND PURPOSE OF STUDY Over the last two decades or so, the whole world has experienced rapid changes and socioeconomic transformations. The socioeconomic changes affected and caused severe stress mainly to isolated, peripheral and rural areas of the world. However, the changes in economic and social culture structure of the world caused decreased farm revenues, changing in the farmland values and high rates of unemployment, leading to mass exodus of the productive forces and lack of balance in the demographics of rural areas (Gannon, 1993). It is obvious from†¦show more content†¦2.2 DEFINITION OF RURAL TOURISM Even though it seems simple to define rural tourism as â€Å"tourism that takes place in the countryside† this definition does not include the complexity of the activities and the different forms and meanings developed in different countries, as well as the number of protagonists participating in rural tourism (Lane, 1993). According to (Lane, 1994) it is difficult to define rural tourism since there is not a systematic source of data in rural tourism and neither World Tourism Organization (WTO) nor the Organization for Economic Cooperation and Development (OECD) have appropriate measures. Nevertheless, Opperman (1996) suggested that the field of rural tourism still lacks a comprehensive body of knowledge and theoretical framework. He argued that this is caused by a) Definitional problems concerning what constitutes rural tourism b) Lack of data sources on small, rural enterprises which makes rural tourism much less obvious and signifies much more tedious work for researchers in their quest for data (Butler et al, 1998:224). Although, the need to differentiate rural tourism from other forms of tourism exists. Even if there is ambiguity between urban and rural and it is certainly difficult to speak about strictly rural characteristics, people still shape images and views of the countryside that differ from those of the town. The social representations of rural areas by the media and Kostas E. Sillignakis – www.sillignakis.comShow MoreRelatedExample of Proposal in Research634 Words   |  3 Pages A PROPOSAL FOR A RESEARCH ON FOOTBALL TECHNOLOGY By Ahmad Zaid Bin Ahmad Affendi B061310020 Nur Aina Mardhia Binti Mohd Esmadi B061310202 Tee Wan Xin B061310090 Saiful Hafizie B. Ramli@Hashim B061310237 Halimaton Saadiah Binti Hakimi B061310222 1.0 INTRODUCTION 1.1 Purpose We propose to complete the research and produce a report on football technology. We also want to explore its functions and effects of this technology towards the football games. Read MoreExample 1 Good Research Proposal With1465 Words   |  6 Pagesï » ¿ Research Proposal Assignment  Title: Research Methodology Code: POPP 5006 Module Leader: Dr H. Oztel; Name: Anonymous Student Number: Pxxxxxxx Word Count: 1200 ( Excluding References ) Date: 17 April 20xx Programme: MSc IBM Table of Content Title 3 Keywords 3 Aims of Research 3 Background 3 Research Questions Read MoreResearch Proposal on Childhood Obesity Essay example979 Words   |  4 Pagesis the commonest problem facing man at present. Though the understanding of hypertension has improved considerably with an increased awareness of the disorder in the general population, the control of hypertension has been dismally poor. 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