Tuesday, January 28, 2020
Coffee Ulbs Essay Example for Free
Coffee Ulbs Essay Coffee is a brewed beverage with a distinct aroma and flavor from the roasted seeds of the coffea plant. Coffee comes in many types of colour such as dark brown,white,beige,black,light brown,and more. Coffee was first discovered in the northeast region of Ethopia. Cofee cultivation first took place in southern Arabia,appears in the middle of the 15th century in the Sufi shrines of Yemen. According to the ancient chronicle,Omar who was known for his ability to cure sick through prayer was once exiled from Mocha,Yemen to a desert cave near Ousab. Starving,Omar chewed berries from nearby shrubbery but found them to the bitter. He tried roasting the seeds to improve the flavor,but they become hard. He then tried boiling them to soften the seeds,which resulted in a fragrant brown liquid. Upon drinking the liquid,Omar was revitalized and sustained for days. As stories of this ââ¬Ëmiracle drugââ¬â¢ reached Mocha,Omar was asked to return and was made a saint. In production of coffee,it consist of many steps such as processing,roasting,grading the roasting seeds,decaffeination,stored,brewing and finally be served. When processing the coffee,the berries of coffee have been traditionally and selectively picked by hand,only the berries at the peak of ripeness would be selected. After that,green coffee is process by one of two methods. Whether by dry process method or wet process method. Then,it will be sorted by ripeness and colour. After that,the seeds are fermented to remove the slimy layer of mucilage still present on the seeds. When the fermentation is finished,the seeds are washed to remove the fermentation residue. Then,the seeds are dried. Finally,the coffee is sorted again and been labeled. The roasting process influences the taste of the beverage by changing the coffee seed both physically and chemically. During roasting,caramelization occurs as intense heat that breaks down starches,changing them to simple sugars that begin to brown,which alters the colour of seeds. Then the seeds will be grading depends on the colour of roasting seeds. It will be labeled as light,medium light,medium,medium dark,dark or very dark. The degree of roast has an effect upon coffee flavor and body. Many methods can remove the caffeine from coffee,but all involve either soaking the green seeds in hot water or steaming them and using a solvent to dissolve caffeine that containing oils. Once roasted,coffee seeds must be stored properly to preserve the fresh taste of the seeds. Coffee seeds must be ground and brewed to create a beverage. Almost all methods of preparing coffee require the seeds to be ground and mixed with hot water long enough to extract the flavor,but without overextraction that draws out bitter compounds. The roasted coffee may be ground at a roaster,in a grocery store or in the home. Then,the coffee may be brewed by several methods such as boiled,steeped,or pressurized. Once brewed,coffee may be served in a variety of ways. As an example,the white coffee was made into dairy product such as milk or cream or dairy substitute or as a black coffee with no such addition. It may be sweetened with sugar or artificial sweetener.
Monday, January 20, 2020
The Diary of Anaïs Nin Essay -- Sexuality
Sex and desire. Few words evoke such complexity of meaning. For some, it is a sexual act. Whereas one might describe it as the sensual pleasure of two bodies fused into one being, another may define it as the fulfillment of animalistic desire, an unleashing of the beast. But, beyond an act charged with various meaning, it can also serve as an identityââ¬âheterosexual, homosexual, bisexual, or transsexual. Whether act or identity, societal dictates define the norm and the deviant. Because of this, the artist who departs from the "acceptable" and embraces the "aberrant," arouses the consciousness of self and society. In doing so, sex and desire become a vehicle, a means of communication between artist and audience, and an object that demands our attention. Whether it is the subtle and sensual language of Anaà ¯s Nin in The Diary of Anaà ¯s Nin (1966), the coarse and explicit vocabulary of Henry Miller in Tropic of Cancer (1934), or the poetic and surrealistic prose of Djuna Barne s in Nightwood (1934), sex and desire, as a vehicle in the literature of these authors, exposes the chaos and confusion within their world and suggests the establishment of a new order for self and/or society. Written between 1931 and 1934, The Diary of Anaà ¯s Nin chronicles one artistââ¬â¢s psychological journey. Deserted by her father as a girl, Anaà ¯s experiences an ââ¬Å"initial shockâ⬠that leaves her ââ¬Å"like a shattered mirrorâ⬠(Nin 103). The shards of glass, each developing a life of their own, come to be the ââ¬Å"several selvesâ⬠of Anaà ¯s (103). Through the pages of The Diary, reflecting upon and dissecting these various selves, she concludes, ââ¬Å"one does not need to remain in bondage to the first wax imprint made on childhood sensibilities. One need not be branded by the fir... ...dea briefly has been to present a resurrection of the emotions, to depict the conduct of a human being in the stratosphere of ideas, that is, in the grip of delirium.â⬠(243). As an artist, his task has been to ââ¬Å"overthrow existing values, to make of the chaos about him an order which is his own, to sow strife and ferment so that by the emotional release those who are dead may be restored to lifeâ⬠(253). While there are those who might disagree with his methods, his language and vivid imagery not only awaken the conscious, but they also provide a much-needed dose of humor in Modernist literature. Works Cited Barnes, Djuna. Nightwood. New York: New Directions Books, 2006. Print. Miller, Henry. Tropic of Cancer. New York: Grove Press, 1961. Print. Nin, Anaà ¯s. The Diary of Anaà ¯s Nin: Volume One 1931-1934. San Diego: Swallow Press and Harcourt, 1966. Print.
Sunday, January 12, 2020
Marriott Corporation: the Cost of Capital Essay
Dan Cohrs of Marriott Corporation has the important task of determining correct hurdle rates for the entire corporation as well as each individual business segment. These rates are instrumental in determining which future projects to pursue and thus fundamentally important for Marriottââ¬â¢s growth trajectory. This case analysis seeks to examine Marriottââ¬â¢s financial strategy in comparison with its growth goals as well as evaluate a detailed breakdown of Marriottââ¬â¢s cost of capital ââ¬â both divisionally and as a whole. Financial Strategy and Growth Marriotââ¬â¢s current financial strategy is in line with its overall goal of steady growth. By building and then promptly selling their hotels to limited partners, the company recoups its costs almost immediately. They then run the hotels, taking a 20% cut of the profits in addition to a 3% management fee. This results in fast, stable returns, which is good for continued growth. They may run into issues with overexpansion in the future, but for the time being, their strategy is sound. The other elements of Marriottââ¬â¢s financial strategy are also in line with their overall goals. By seeking projects that would increase shareholder value and repurchasing undervalued shares, they ensure that the value of their equity does not decrease. When coupled with the use of debt in the companyââ¬â¢s capital structure, they are creating a good framework for future growth. Cost of Capital ââ¬â Lodging and Restaurant Divisions We begin with an analysis of hurdle rates for the Lodging and Restaurant divisions, for which public comparable company figures are provided, to back into cost of capital for Contract Services in the next section, for which public comparables are not available. Restaurant D/V D/E à ²lev ered à ²unlev ered Churchââ¬â¢s Chicken 4.0 % 0.04 0.75 0.73 Frischââ¬â¢s 6.0 % 0.06 0.60 0.58 Collins Foods 10.0 % 0.11 0.13 0.12 Lubyââ¬â¢s Cafeterias 1.0 % 0.01 0.64 0.64 McDonaldââ¬â¢s 23.0 % 0.30 1.00 0.86 Wendyââ¬â¢s Int. 21.0 % 0.27 1.08 0.94 Rf 8.72 % Market Premium 7.92 % Median à ²unlev ered 0.685 Target Debt % 42 % à ²lev ered 0.962 Cost of Equity 16.57 % Cost of Debt 10.52 % WACC 12.08 % Lodging D/V D/E à ²lev ered à ²unlev ered Hilton 14.0 % 0.16 0.88 0.81 Holiday 79.0 % 3.76 1.46 0.47 La Quinta 69.0 % 2.23 0.38 0.17 Ramada 65.0 % 1.86 0.95 0.47 Rf 8.95 % Market Premium 7.92 % Median à ²unlev ered 0.468 Target Debt % 74 % à ²lev ered 1.213 Cost of Equity 18.56 % Cost of Debt 10.05 % WACC 8.98 % For these two divisions, we found the unlevered beta for each company in the divisionââ¬â¢s peer set, then relevered the median of this set with respect to Marriottââ¬â¢s target debt percentage of 74% and 42% for Lodging and Restaurant divisions, respectively, as a proxy for Marriottââ¬â¢s Lodging levered beta. The risk-free rates are based on U.S Treasury interest rates: we used the 30-year for Lodging and the 10-year for Restaurant due to the longevity of the assets in each respective division. Lodging assets consist mostly of real estate and have lives spanning decades, while restaurants are more likely to have a life cycle closer to 10 years. The geometric average in 1987 for the spread between the S&P 500 and U.S. Government Bonds at 7.92% is used as the market risk premium in all cases, and the cost of debt is calculated by adding the debt rate premium for each division to each divisionââ¬â¢s risk free rate. A tax rate of 44.1% is extrapolated by dividing income tax expense by EBT in the historical financials. With the entire infrastructure in place, we can calculate each divisionââ¬â¢s cost of equity through the CAPM model: Cost of Capital ââ¬â Contract Services Division Comparable companies are not given for the Contract Services Division, but information about the division can be backsolved using some simple algebra as we are given Marriottââ¬â¢s balance sheet breakdown by segment in Exhibit 2: Since it is given that Marriottââ¬â¢s unlevered beta is .97, its tax rate is 44.1%, and has 60% debt in its capital structure, we can unlever to see that Marriott as an entire firm has an unlevered beta of .79. Assuming that Marriottââ¬â¢s unlevered beta can be calculated as a weighted average of its divisionsââ¬â¢ betas based on identifiable assets, we can find Contract Services unlevered beta by solving: Using some algebra, this yields an unlevered beta of 1.55 for Contract Services. Relevering with the 2/3 desired debt-to-equity ratio yields a levered beta of 2.13. This time, we use the 1-day risk-free rate due to the even shorter lifespan of contracts. Cost of Capital ââ¬â Marriott as a Whole There are several ways to approach Marriottââ¬â¢s cost of capital as an entire firm. One way is to use CAPM to find its cost of equity, long-term interest rates for the cost of debt, and weigh according to its capital structure to find WACC. Under this method, we lever the previously found firm-wide à ²U of .79 to the desired 3/2 debt-to-equity ratio to find a cost of equity of 17.12%. Next, we apply the CAPM using the 10-year Treasury for 1987 Assets % of total à ²unlev ered Lodging 2777.4 60.6 % 0.47 Contract Services 1237.7 27.0 % Restaurants 567.6 12.4 % 0.68 Total 4582.7 100.0 % Contract Services Rf 6.90 % Market Premium 7.92 % à ²unlev ered 1.550 Target Debt % 40 % à ²lev ered 2.131 Cost of Equity 23.78 % Cost of Debt 8.30 % WACC 16.12 % the risk-free rate and the one-year arithmetic return for 1987. We use the arithmetic rather than geometric since CAPM is a one-period model. For Marriottââ¬â¢s cost of debt, we add the credit spread of 1.3% to the ten-year Treasury yield of 8.72%. Plugging all these variables into CAPM, we arrive at a WACC of 10.53%. Another method to finding Marriottââ¬â¢s cost of capital is by taking a weighted average of its three segments. Since its three segments have different business models ââ¬â it may be helpful to see the cost of capital as a mix of its three divisions rather than an aggregate Marriott unit. Weighing each division by the same weights in the Contract Services section, we calculate that WACC is 11.3% A couple of items to note on Marriottââ¬â¢s firm-wide cost of capital are noted here. Marriottââ¬â¢s WACC measures the cost of capital for the whole Marriott Corporation. Marriott has three lines of business ââ¬âeach line of service has its unique cost of deb t and beta, so when valuing investments in those three service lines, we would use their own WACC instead of using Marriottââ¬â¢s WACC. If the firm only uses one hurdle rate for evaluating investment opportunities in each line of business, it may accept or reject some investment project improperly. From the question below we already found that the WACC for lodging and restaurants is not the same. So for example, if just using one hurdle rate, like 10%, to evaluate the project among these two line of service, the lodging service may reject this project while the restaurant service may accept it. Appendix Below are the costs of equity, debt, and capital for all of Marriott as well as its three divisions. Weight WACC Lodging 0.60606 8.98 % Contract Services 0.27008 16.12 % Restaurants 0.12386 12.08 % 11.30 % Contract Marriott Lodging Restaurant Services Cost of Debt 10.02 % 10.05 % 10.52 % 8.30 % Cost of Equity 17.12 % 18.56 % 16.57 % 23.78 % Cost of Capital 10.53 % 8.98 % 12.08 % 16.12 %
Saturday, January 4, 2020
The Story of an Hour by Kate Chopin - 1161 Words
Feminism is played out in a major way in Kate Chopinsââ¬â¢ ââ¬Å"The Story of an Hour.â⬠The story portrays a story about the lack of freedom that all woman had in the 1800ââ¬â¢s. The word feminism as defined in the Merriam-Webster Dictionary as the theory of the political, economic and social equality of the sexes. A womanââ¬â¢s job and duty in the 1800ââ¬â¢s was to tend to the needs of their husbandââ¬â¢s needs. In ââ¬Å"The Story of an Hourâ⬠Mrs. Mallard, one of the main characters, was told about her husbandââ¬â¢s death and she was initially very emotional. Her sadness was quickly turned into a burst of joy because she felt a sense of freedom. The story takes a very weird and ironic twist because her husband was really not dead and when Mrs. Mallard finds out about this she regretted abandoning her moment of freedom. If we were looking at this story through the historical and feminist lenses one would suggest that this story is about a male dominate d society in the 1800s. This male dominated society caused the woman to have a lack of freedom and really made it hard for woman to have a self-identity. Males were the dominant gender during the 1800s. Woman had absolutely no rights and the reality was that feminism did not exist. One of the things that was really frowned upon in the 1800s were divorces. In fact if there was a divorce, everything would be given to the male. In the Declaration of Sentiments, Stanton enumerated specific complaints concerning the oppressed status of women in American society:Show MoreRelatedThe Story Of An Hour By Kate Chopin1241 Words à |à 5 Pagesââ¬Å"The Story of an Hourâ⬠by Kate Chopin is a wonderful short story bursting with many peculiar twists and turns. Written in 1894, the author tells a tale of a woman who learns of her husbandââ¬â¢s death, but comes to find pleasure in it. Many of the elements Kate Chopin writes about in this story symbolize something more than just the surfac e meaning. Through this short story, told in less than one thousand one hundred words, Kate Chopin illustrates a deeper meaning of Mrs. Mallardââ¬â¢s marriage with herRead MoreThe Story Of An Hour By Kate Chopin855 Words à |à 4 PagesThe Story of an Hour In the ââ¬Å"Story of an Hourâ⬠by Kate Chopin, is about pleasure of freedom and the oppression of marriage. Just like in Kate Chopinââ¬â¢s story, inside most marriages, even the ones that seem to be the happiest, one can be oppressed. Even though, one might seem to be happy deep inside they miss the pleasure of freedom and living life to the fullest. Just like, in this story Mrs. Mallard feels trapped and when she hears about her husbandââ¬â¢s death she first feels distraught, but ultimatelyRead MoreThe Story Of An Hour By Kate Chopin1457 Words à |à 6 PagesEmotions and Death Everyone who reads a story will interpret things slightly different than the person who reads it before or after him or her. This idea plays out with most every story, book, song, and movie. These interpretations create conflict and allow people to discuss different ideas and opinions. Without this conflict of thought there is no one devoting time to debate the true meaning of a text. Kate Chopinââ¬â¢s ââ¬Å"The Story of an Hourâ⬠tells about a woman who is informed of her husbands deathRead MoreThe Story Of An Hour By Kate Chopin987 Words à |à 4 PagesIn Kate Chopinââ¬â¢s short story, ââ¬Å"The Story of an Hourâ⬠readerââ¬â¢s see a potentially long story put into a few pages filled with rising action, climax and even death. In the beginning of the story, character Louise Mallard, who has a heart condition, is told of the death of her husband by her sister and one of her husbandââ¬â¢s friends. Afterwards Mrs. Mallard is filled with emptiness and then joy of freedom. This joy of freedom is actually what consequently leads to her death in the end when she discoversRead MoreThe Story Of An Hour By Kate Chopin1061 Words à |à 5 PagesThroughout the short story, ââ¬Å"The Story of an Hourâ⬠, readers are introduced to characters whose lives change drastically in the course of this writing. Through Kate Chopinââ¬â¢s story we can identify many different themes and examples of symbolism in her writing. Chopinââ¬â¢s choice of themes in this writing are no surprise due to the time frame of which this story was written. Chopin often wrote stories with of womenââ¬â¢s rights, and is noted as one of Americaââ¬â¢s first open feminists. As this story of an ill, helplessRead MoreThe Story Of An Hour By Kate Chopin972 Words à |à 4 Pagesââ¬Å"The Story of an Hourâ⬠by Kate Chopin expresses Ms. Mallardââ¬â¢s feelings towards her husbandââ¬â¢s death in an appalling train accident. Due to her bad heart, her sister Josep hine had to be the bearer of bad news and approach his death gently to her. According to the quote, ââ¬Å" But now there was a dull stare in her eyes, whose gaze was fixed away off yonder on one of those patches of blue sky. It was not a glance of reflection, but rather indicated a suspension of intelligent thoughtâ⬠, it lets us know thatRead MoreThe Story Of An Hour By Kate Chopin998 Words à |à 4 Pagesââ¬Å"The story of an hourâ⬠by Kate Chopin was a story that was ironical yet profoundly deep. As a student I have been asked to read ââ¬Å"a story of an hourâ⬠many times, and every time Iââ¬â¢m surprised by how I enjoy it. People can read thousands of stories in their life times and only a handful will every stand out to them, stories that can draw out an emotion or spark a thought are the ones that will standout more. For me and ââ¬Å"a story of an hourâ⬠the thought of freedom is what draws me the most as a teenageRead MoreThe Story Of An Hour By Kat e Chopin1542 Words à |à 7 PagesIn the short story, ââ¬Å"Story of an Hourâ⬠, Kate Chopin writes about a woman with heart trouble, Mrs. Mallard, who, in finding out about the death of her husband, Mr. Mallard, experiences some initial feelings of sadness which quickly transition into the exhilarating discovery of the idea of a newfound freedom lying in front of her. When it is later revealed that her husband is not actually dead, she realizes she will not get to taste that freedom. The devastation kills her. What Mrs. Mallard goes throughRead MoreThe Story of an Hour by Kate Chopin596 Words à |à 2 PagesIn ââ¬Å"The Story of an Hour,â⬠Kate Chopin focuses on the idea of freedom throughout the story. Mrs. Mallard is a lonely wife who suffers from heart trouble. She is told by her sister Josephine and her husbandââ¬â¢s friend Richards that her husband has passed away in a train accident. She locks herself in a room expecting to be devastated, but instead feels freedom. Later, she exits her room and her husband walks through the door, causing her to die of a heart attack. Chopin uses this story to demonstrateRead MoreThe Story Of An Hour By Kate Chopin886 Words à |à 4 Pages In Kate Chopin ââ¬Å"The Story of an Hourâ⬠, the reader is presented with the theme of prohibited independence. In Kate Chopin ââ¬Å"The Stormâ⬠, the scenery in this story builds the perfect atmosphere for an adulterous affair. The importance of these stories is to understand the era they occurred. Kate Chopin wrote stories with exceptional openness about sexual desires. In ââ¬Å"The Stormâ⬠, a short story written by Kate Chopin in a time when women were expected to act a certain way and sexual cravings was considered
Friday, December 27, 2019
Thursday, December 19, 2019
Case Study Building A Policy Briefing - 1699 Words
ASSIGNMENT3: BUILDING A POLICY BRIEFING Stephana PEA Prof. Aaron Watches May 8, 2016 Submitted on April 11, 2016 University of Baltimore- Spring Quarter 2016 What can the Baltimore government/policy makers do about homeless in Baltimore? The purpose of this paper is to evaluate the policy and actions that can be taken to end the homelessness issue. Homeless is a serious multi-faceted issue that requires the involvement of many agencies, policymakers, governments and faith-organizations. Having no home is a miserable experience, causing health problems, exacerbating existing health problems, and complicating treatment. It is so difficult to find a safe place to stay, obtain enough food, keep clean, and stay out of the way of the police and even sleeping on the streets, on peopleââ¬â¢s sofa and in doorways, Baltimoreââ¬â¢s homeless population has been increased in recent years. There are several answers to this issue, and its depend on the individualââ¬â¢s matters. One of the solutions to end homelessness in Baltimore city is housing, trying to re-housing the homeless people in a safe environment. Second, ending poverty, next another solution to homelessness is guaranteeing that everybody has the health and c onfirmatory services that they need to stay housed. For individuals who are mentally sick or physically disabled. It is often the case that overburdened family members cannot or do not wish to care for them. This reduces their options to abandoned buildings orShow MoreRelatedThe Employees After A Downsizing Case Study Essay1707 Words à |à 7 Pages Case Study Description The reenergizing employees after a downsizing case study, explains the potential effects of downsizing a company, on both employees and the manager. Andrea Zuckerman is the editor in chief of Blaze and the person who must relay the message to the entire company. It is made clear throughout the case that Andrea does not agree with this downsizing and feels that it is wrong. However, due to the newspaper industry dwindling away and many people now reading the news from aRead MoreBriefing paper on rural housing1482 Words à |à 6 Pagesï » ¿ Table of Contents Briefing paper on Rural Housing Statement Britain has experienced a series of affordable housing crisis in the early 1980s and early 1990s (Bramley, 1994). As Andrew Stonell (2010) stated ââ¬Å"Localism works-all over the country there are villages very keen to have low-cost housing for local people and they are prevented by the planning system from having it.â⬠This briefing paper refutes Stonellââ¬â¢s claim and is written to the North Eastern Farming and Rural AdvisoryRead MoreHrm Policy As The Firm Transcends Across Its National Borders Essay1739 Words à |à 7 PagesÃ¢â¬Æ' 1. Examine the changes in the HRM policy as the firm transcends across its national borders? In recent years due to the factors like globalization and removal of trade restrictions have created fierce competition in domestic market for the well-established domestic firms. So, this competition has encouraged many domestic producers to enter into the international business through exporting their product to the different parts of the world or licensing or joint ventures to gain higher profit. ByRead MoreLeadership And Communication Strategies For Effective Leadership882 Words à |à 4 Pagesof communication from the top of the food chain, where he resides as CEO in this case, to the bottom of the food chain in successive levels of leadership. Therefore, communication is necessary tool for effective leadership. Communication Strategies for Effective Leadership Time and time again through studies, researchers have found communication to be one of the most important skill for leadership. Several studies such as Mumford, campion and morgeson (2007) where 1000 various level of managersRead MoreSample Letter Essay800 Words à |à 4 Pagescommunities at home. My role in ActionAid has seen me document the challenges community faced as well as their inspiration, and convert those material into audience friendly products in various formats, including newsletter, briefing paper and donorsââ¬â¢ reports. 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Out of 26 major recommendations, oneRead MoreThe Module 3 Case Assignment888 Words à |à 4 PagesThe Module 3 Case assignment is about a young nurse named Christy and her interactions between two different Romani patients. The case study highlights the differences in perception of a culture, and how that impacts the attitude of the provider staff and the health care the patients receive. Additionally, the case study shows how Jacqueline, the Clinical Nurse Manager, is trying to fix the overall cultural competence with the hospital staff to better accommodate the influx of Romani patients inRead MoreCurtin University Unit Outline for Scim2328 Words à |à 10 PagesCurtin Business School School of Information Systems Unit Outline 13474 Supply Chain Information Management 201 Trimester 2A, 2013 Unit study package number: Mode of study: Tuition pattern summary: 13474 Internal Lecture: 1 x 1.5 Hours Weekly Computer Laboratory: 1 x 1.5 Hours Weekly This unit does not have a fieldwork component. Credit Value: Pre-requisite units: Co-requisite units: Anti-requisite units: Result type: Approved incidental fees: Unit coordinator: 25.0 Nil Nil 11955 (v.0) IntroductionRead MorePublic Environmental Awareness and Education1615 Words à |à 7 Pagesuse of the media, awareness raising campaigns, incorporation of environmental issues in mainstream education, increasing awareness and education in target groups and encouragement of public participation in environmental matters. As the following case studies illustrate, many sectors of society are involved in developing and delivering educational courses and public awareness campaigns. These include Governmental institutions at the national, regional, and local levels; domestic and international NGOs;Read MoreEst1 Task 21409 Words à |à 6 Pagesour upmost desire to comply with rules and laws pertaining to our business, and to hold our values at a spectacular level. Our company values include responsibility, equality, honesty, confidentiality, respect, and integrity. These values are the building block of our company, and should be followed by all employees, management, and any persons associated with our business. By adhering to the code of conduct, our work environment will be comfortable and reliable, and will help avoid unethical behavior
Tuesday, December 10, 2019
Has Gallo Proven The Role Of Hiv In Aids Essay Example For Students
Has Gallo Proven The Role Of Hiv In Aids? Essay Introduction In 1982, Robert Gallo from the National Cancer Institute in the USA, put forward the hypothesis that the cause of AIDS is a retrovirus. One year later, Myron Essex and his colleagues (1) found that AIDS patients had antibodies to the Human T-cell Leukemia virus Type-1 (HTLV-I), a virus discovered by Gallo a few years earlier. At the same time, Gallo and his colleagues (2) reported the isolation of HTLV-I from AIDS patients and advocated a role for this retrovirus in the pathogenesis of AIDS. This hypothesis however, was not without a few problems: 1. While HTLV-I was accepted to induce T4-cell proliferation and cause adult T-cell leukaemia,(3) the hallmark of AIDS was T4-cell depletion, and the incidence of leukaemia in AIDS patients was no higher than in the general population; 2. The highest frequency of antibodies to this virus was found in Japan, yet no AIDS cases had been reported from that country;(4) 3. In the same month in which Gallos and Essexs groups reported their data, Luc Montagnier and his colleagues from the Pasteur Institute, described the isolation of a retrovirus, later known as Lymphadenopathy Associated Virus (LAV), from the lymph nodes of a homosexual patient with lymphadenopathy.(5) Although this virus was similar to HTLV-I, one of its proteins, a protein with a molecular weight of 24,000 (p24), did not react with monoclonal antibodies to the HTLV-I p24 protein. Samples of this virus were, on several occasions, sent to Gallos laboratory. In May 1984, Gallo, Popovic and their colleagues published four papers in Science in which they claimed to have isolated from AIDS patients, another retrovirus, which they called HTLV-III.(6,7,8,9) On the 23rd of April 1984, before the Science papers were published, Gallo and Margaret Heckler, the then Health and Human Services Secretary called a press conference to announce that Gallo and his co-workers had found the cause of AIDS and had developed a sensitive test to show whether the AIDS virus is present in blood. In 1985, the Pasteur Institute alleged that Gallo had misappropriated LAV in developing the blood test. The ensuing conflict, which reached the American courts, was eventually settled by a negotiated agreement signed in 1987 by Gallo, Montagnier, US President Reagan and French Premier Chirac. The agreement declared Gallo and Montagnier to be co-discoverers of the AIDS virus, presently known as the Human Immunodeficiency Virus (HIV). Nevertheless, the misappropriation conflict drew the attention of John Crewdson, an investigative journalist, and US Senator John Dingell. In November 1989, Crewdson published a lengthy article in the Chicago Tribune newspaper, With allegations that Robert C. Gallo stole from French scientists the virus he discovered to be the cause of AIDS. (10) This led to a National Institute of Health (NIH) internal inquiry into the allegation with an outside committee of expert but disinterested parties led by Yale biochemist Frederic Richards to oversee the activity of the internal panel.(11) Following the inquiry, which was viewed as a fact-finding mission, the Richards committee insisted on a formal investigation on suspect data in one of four seminal papers published by Gallos lab in Science on 4 May 1984.(12) In this paper, the first of a series of four, with Mikulas Popovic the principal author, their appears to be differences between what was described in the paper and what was done. (10) A draft report of the formal investigation written by NIH Office of Scientific Integrity (OSI), was published in September 1991. In the draft report, Popovic is accused of misconduct for misstatements and inaccuracies that appeared in the paper, and that Gallo, as laboratory chief, created and fostered conditions that give rise to falsified/ fabricated data and falsified reports. However, Gallos actions were not considered to meet the formal definition of misconduct.(13) The final draft report of the OSI, completed in January 1992, was immediately criticised by the Richards Panel as well as Senator Dingell. This led to a review of the OSI report by the Office of Research Integrity (ORI), which found Gallo guilty of scientific misconduct. Nonetheless, the scientific misconduct is said not to negate the central findings of the 1984 Science paper. Asian Philosophies of Critical Thinking Essay Among the recipients of WBI blood, 36% were WBI 6 months after transfusion, but so were 42% of individuals who received WB-negative samples. Both donors and recipients of blood remained healthy. They concluded that WBI patterns are exceedingly common in randomly selected donors and recipients and such patterns do not correlate with the presence of HIV-1 or the transmission of HIV-1, most such reactions represent false- positive results; 3. Antibodies to p24 have been detected in 1 out of 150 healthy individuals, 13% of randomly selected otherwise healthy patients with generalised warts, 24% of patients with cutaneous T-cell lymphoma and prodrome and 41% of patients with multiple sclerosis;(52) 4. Ninety seven percent of sera from homosexuals with ITP and 94% of sera from homosexuals with lymphandenopathy or AIDS contain an antibody that reacts with a 25Kd membrane antigen found in platelets from healthy donors and AIDS patients, as well as a 25 Kd antigen found in green-monkey kidney cells, human skin fibroblasts, and herpes simplex cultured in monkey kidney cells. This reaction was absent in sera obtained from non-homosexual patients with ITP or non-immune thrombocytopenic purpura;(48) 5. Conversely, the p24 antigen is not found in all HIV positive or even AIDS patients. In one study, the polymerase chain reaction (PCR) and p24 were used to detect HIV in patients at various CDC stages from asymptomatic to AIDS. p24 was detected in 24% patients and HIV RNA in 50%;(53) 6. In another study, In half of the cases in which a subject had a positive p24 test, the subject later had a negative test without taking any medications that would be expected to affect p24 antigen levels the test is clinically erratic and should be interpreted very cautiously.(54) Thus the finding of viral particles in the AIDS cultures/co- cultures, RT and proteins which react with AIDS related sera in the material from the supernatant or cell lysates which in sucrose density gradients bands at 1.16 gm/ml, cannot be considered synonymous with the isolation or even the detection of a retrovirus. Even if a retrovirus is isolated from in vitro cultures/co-cultures from tissues from AIDS patients, this does not, by itself, constitute proof of the existence of the virus in vivo, (in AIDS patients), and even less that the retrovirus has been exogenously acquired. This is because: 1. At present, it is generally accepted that one of the most striking features that distinguish retroviruses from all other animal retroviruses is the presence, in the chromosomes of normal uninfected cells, of genomes closely related to, or identical with those of infectious viruses. The human genome, in addition to other proviral sequences, is known to contain both HTLV-I (55,56) and HIV (57) sequences. Depending on conditions, the proviral genome remains unexpressed or part or all of it may be expressed. The latter may or may not lead to the assembly of viral particles (endogenous retrovirus).(17) In animal cultures, healthy non-virus producing cells sooner or later spontaneously release retroviruses.(20) The appearance and yield can be increased by (i) mitogenic stimulation;(58) (ii) co-cultivation techniques;(59) (iii) cultivation of cells with supernatant from non-virus producing cultures.(60) According to one eminent retrovirologist, George Todaro, the failure to isolate endogenous viruses from certain species may reflect thelimitation of in vitro cocultivation techniques;(61) 2. Gallos team, like everybody else: (i) isolated HTLV-III (HIV) from cell cultures; (ii) isolated HTLV-III from mitogenically stimulated, activated cell cultures; 3. In addition, Gallo and his colleagues also used co-cultivation techniques; 4. The first HTLV-III isolation was from the HT (H4, H9, H17) cell line. Reading Gallo and his colleagues first paper, one surmises that the HT cell line was established in Gallos laboratory. The Gallo inquiry revealed that the HT cell line is in fact HUT78, a cell line established in another laboratory from a patient with mature T4-cell leukaemia, a disease which Gallo claims is caused by the exogenous retrovirus, HTLV-I.(3) If so, then all HT cell cultures, and the clones derived from it, infected with HTLV-III or non-infected, and the material from these cultures which bands at 1.16 gm/ml, should contain HTLV-I, and thus RT and retroviral particles. Furthermore, because about 25% of AIDS patients have antibodies to HTVL-I,(1) and the immunogenic proteins of HTLV-I and HIV have the same molecular weights, then approximately 25% of the non-infected HT (H4, H9, H17) cultures in addition to RT and particles, should have, in the Western blot, the same bands as those of the HTLV-III infected cultures. Thus, these WBs will erroneously appear positive for HTLV-III. Proof that HTLV-III (HIV) is causally linked to AIDS. Gallo claims, a claim accepted by the vast majority of AIDS researchers, that in the May 1984 Science papers he and his colleagues presented unambiguous evidence that this and this alone was the cause of AIDS.(62) A minimum requirement for making such a claim should be presentation of the following evidence: 1. That all AIDS patients are infected with HTLV-III; 2. Infection with HTLV-III leads to T4-cell depletion, given the assumption that HTLV-III leads to the clinical syndrome by its T4 cytotoxicity. The evidence for the existence of HTLV-III was viral isolation and ELISA antibody tests. Even if one assumes that the data presented represents true isolation, the virus was isolated from less that half (10/21) of AIDS patients with opportunistic infections, and in less than one third (13/43) with Kaposis sarcoma, then and now the two most characteristic AIDS diseases. Even if the virus could have been isolated from all patients, given the nature of retroviruses and the method used for HTLV-III isolation (cultures, mitogenic stimulation, co- cultivation) the possibility cannot be excluded that the virus did not exist in vivo (in AIDS patients), and that it was a provirus whose expression was facilitated by the culture conditions. The only method used to prove HIV infection in vivo was the antibody tests. Such a test can only be used only after its specificity has been proven by use of the only possible gold standard, the virus itself. This has not been done. Furthermore, the antibody test used by Gallo was ELISA, at present known to be non-reproducible and non-specific. In a study of 1.2 million healthy military applicants conducted by Colonel Donald Burke and his colleagues,(63) it was found that although approximately 1% of all individuals had an initial positive HIV ELISA, only 50% of repeat ELISAs were positive. Of the latter, only approximately one third were associated with two subsequent positive WBs. In Russia, in 1990, out of 20,000 positive ELISAs only 112 were confirmed using the WB as a gold standard. In 1991, of approximately 30,000 positive ELISAs, only 66 were confirmed.(64) Nowhere in the four Science papers was HTVL-III cytotoxicity mentioned. The only reference to any cellular abnormalities or pathology in general is in the first paper where one reads: The virus positive cultures consistently showed a high proportion of round giant cells containing numerous nuclei (Fig. 1a). These cells resemble those induced by HTLV-I and -II except that the nuclei exhibit a characteristic ring formation. (Fig. 1a is a light microscopic examination of clone H4/HTLV-III). The H4 clone was obtained from the HT cell line using irradiated mononuclear cells from peripheral blood of a healthy blood donor as a feeder. At present, it is known that the HT cell line and thus H4 are HUT78, derived in 1980 from a patient with mature T4-cell leukaemia,(65,66) However, other cell lines derived from patients with the same clinical syndrome are known to exhibit similar morphologies including multinucleated giant cells.(67) Thus the cellular morphological characteristics observed in the first paper may have been an intrinsic property of the HT cell line, or the result of the culture conditions, or both, and not due to HTLV-III. Finally, Gallo and his colleagues did not provide any data on the immunological status of those individuals from whom viral isolation was attempted, and no data was presented proving that: 1. HTLV-III (HIV) is both a necessary and sufficient cause of T4- cell depletion; 2. T4-cell depletion is both necessary and sufficient for the appearance of the AIDS indicator diseases. Conclusions The data and arguments that have been presented by Gallo and his colleagues do not constitute proof of HIV isolation or an unambiguous role for HIV in the pathogenesis of AIDS. Although some researchers currently use methods of viral isolation essentially the same as that described by Gallos group, most use less rigorous methods including singleton detection of p24 (by antibody techniques), or RT. Notwithstanding, with all of these techniques, including that described by Gallo and his colleagues, which itself seen to be greatly problematic, HIV cannot be isolated from 20%-70% of HIV positive and AIDS patients(68,69) Thus we are faced with a problem of considerable importance. The HIV antibody tests, both ELISA and WB, the only routinely used tests proving the existence in vivo of HIV, have yet to be verified against the only suitable gold standard, viral isolation. The available evidence suggests that this long overdue but most basic requirement of test evaluation is likely to prove an immense problem, and while the HIV antibody tests are useful prognostic markers in the high risk groups, their use as diagnostic and epidemiological tools for HIV infection is questionable.References 1. Essex M, McLane MF, Lee TH, et al. Antibodies to Cell Membrane Antigens Associated with Human T-Cell Leukemia Virus in Patients with AIDS. Science 1985;220:859-862. 2. Gallo RC, Sarin PS, Gelmann EP, et al. Isolation of Human T- Cell Leukemia Virus in Acquired Immune Deficiency Syndrome (AIDS). Science 1983;220:865-867. 3. Gallo RC. The First Human Retrovirus. Sci Am 1986; 255:78-88. 4. Marx JL. Human T-Cell Leukemia Linked to AIDS. Science 1983;220:806-809. 5. Barre-Sinoussi F, Chermann JC, Rey F, et al. Isolation of a T-Lymphotrophic Retrovirus from a patient at Risk for Acquired Immune Deficiency Syndrome (AIDS). Science 1983;220:868-871. 6. Popovic M, Sarngadharan MG, Read E, et al. Detection, Isolation,and Continuous Production of Cytopathic Retroviruses (HTLV-III) from Patients with AIDS and Pre-AIDS. Science 1984;224:497-500. 7. Gallo RC, Salahuddin SZ, Popovic M, et al. Frequent Detection and Isolation of Cytopathic Retroviruses (HTLV-III) from Patients with AIDS and at Risk for AIDS. Science 1984;224:500-502. 8. Schupbach J, Popovic M, Gilden RV, et al. Serological analysis of a Subgroup of Human T-Lymphotrophic Retroviruses (HTLV-III) Associated with AIDS. Science 1984;224:503-505. 9. Sarngadharan MG, Popovic M,Bruch L, et al. Antibodies Reactive to Human T-Lymphotrophic Retroviruses (HTLV-III) in the Serum of Patients with AIDS. Science 1984:224:506-508. 10. Culliton BJ. Gallo Inquiry Takes Puzzling New Turn. Science 1990:250:202-203. 11. Culliton BJ. Inside the Gallo Probe. Science 1990;248:1494-1498. 12. Hamilton DP. What Next in the Gallo Case? Science 1991;254:944-945. 13. Palca J. Draft of Gallo Report Sees the Light of Day. Science 1991;253:1347-1348. 14. Cohen J. HHS: Gallo Guilty of Misconduct. Science 1993:259:168-170. 15. Gallo RC, Sarin PS, Kramarsky B. et al. First isolation of HTLV-III. Nature 1986;321:119. BibliographyThe evidence that Robert Gallo and his colleagues presented on 4th May 1984 regarding HTLV-III (HIV) isolation and the role of HIV in the pathogenesis of AIDS is critically analysed. It is concluded that the evidence does not constitute proof of the isolation of a retrovirus, that the virus is exogenous or that the virus is causally related to AIDS. Medicine Essays
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