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barbara boxer resume Barbara Boxer (born 1940) is a Democratic Senator from California. Barbara Boxer was one of six women elected to a process, the U.S. Senate in 1992. Management Paper Project Team Term. Representing California as a Democrat, she was part of a larger movement that swept an increased number of describe a process, women into positions of power within the government. A 10-year veteran of Congress, Boxer rose through her energetic and combative style, and her fealty to the liberal causes which had first inspired her entrance into on pivotal issues storytelling politics#8212;feminism and environmentalism chief among them. The product of a conventional background and a process essay upbringing, Boxer was inspired by the social upheavals of the 1960s to research paper, look beyond her home and family to make her mark on describe the world at large. Paper Team. Boxer's origins and early years gave little hint of the career she would eventually pursue.
She was born in a process essay, Brooklyn, New York, the child of immigrants, in 1940. Boxer later recalled a conventional and happy middle-class childhood, which included education in in the, the local public schools. As a child of the '50s, Boxer wrote in her memoir, Strangers in the Senate, she wore cinch belts and describe essay layers of writing, crinolines, as well as hoop skirts, to a process, conform to the dictates of fashion. Nonetheless, in apush thesis, high school, she and a friend took on the job of describe, coaching the boys' baseball team, an unconventional choice. In The. Boxer made another unconventional choice when she entered Brooklyn College in 1958 and a process became one of the few women at term, the institution to chose a major of economics, instead of a process essay, education. For her minor, Boxer chose political science. She also served as a cheerleader for top 10 creative, the Brooklyn College basketball team. In her final year of a process essay, college, at top 10 writing schools, age 21, Barbara Levy married Stewart Boxer, another student, who was then 23. The two moved into a one-room efficiency apartment at the back of a building on describe a process essay Ocean Boulevard, paying $90 a month in rent. When the building's owner failed to mla reference format paper, provide promised amenities, such as a carpeted and painted lobby, the energetic Boxer circulated a petition in describe a process essay, the building to pressure the landlord into two kinds fixing things up. After graduating from a process, college Boxer sought a job in creative writing schools, the New York financial world to support her husband while he completed his law degree at Fordham University.
She tried to enter one of the essay, stockbroker training programs run by two kinds amy tan the big Wall Street firms, but was turned down on describe a process essay the basis of her sex. Apush Thesis. Boxer then took a job as a secretary, and describe studied for the stockbroker's exam independently. Mla Reference Research. Even after she passed, Boxer was not allowed to a process, sell securities and earn commissions, so she left her job and took a position with a firm that would allow her to do so. Boxer was working as a stockbroker when the event that she later identified as the birth of essays on pivotal issues in contemporary storytelling, her political consciousness took place: the assassination of President John F. Kennedy in a process, 1963. With this event, and the later political assassinations of the 1960s, Boxer began to introductions essay, look beyond her own private life and aspirations to address larger social issues and concerns. In 1965 Boxer moved with her husband to northern California. The couple had been determined to own a house and raise a family, and they felt that real estate was more affordable there than in the New York metropolitan area.
While her husband was completing his exams at describe essay, Fordham, Boxer quit her job and relocated to argumentative essay, San Francisco to find a house. She was seven months pregnant with her first child at describe essay, the time, and gave birth to her son#8212;two months prematurely#8212;the day after she arrived. Essay Outline Model C. Boxer and describe her husband soon settled in San Francisco, and their second child, a daughter, came into the family in 1967. Although Boxer later recalled that she was primarily concerned with her family life during that time, she and her husband opposed the war in Vietnam, and felt strongly enough about their position to apush thesis, take part in a peace march, which wound through the city to Golden Gate Park. Describe A Process Essay. Also in 1967, Boxer and essays in the military her husband moved to describe essay, the city suburbs, buying a $40, 000 house in Marin County, north of the city.
This area would later become the introductions, basis of her political constituency. The year after they had moved to Marin, Boxer witnessed the assassination of Robert Kennedy live on television, and describe a process essay this violent act, she later recalled, shocked her forever from paper, her routine private life. Joining with other women from describe a process, her community, who were young, college-educated mothers like her, Boxer and essays in the military her friends in a process, the town of Greenbrae embarked on issues storytelling a number of social initiatives. A Process Essay. Among their first efforts was a program called Education Corps of Marin, designed to mla reference format research, train high school drop-outs for jobs. This program was eventually taken over by the local school system. Describe. In addition, Boxer became involved in the environmental movement as well as in two kinds amy tan paper, anti-war activities. In 1970 she oversaw publicity for describe essay, a campaign to put a peace initiative on essay outline model the ballot, which, surprisingly, carried the describe, day. On Pivotal. She worked for other local ballot initiatives and for progressive candidates. Marin Community Video and describe the Marin Alternative, a progressive, grassroots, political network, also earned her attention. Term. At the same time Boxer devoted her energy to describe a process, a number of creative writing schools, women's and a process children's groups, helping to in the military, found the Kentfield After School Child Care Center, and taking part in describe, Woman's Way, a women's support group.
On the amy tan paper, strength of describe a process essay, these activities, Boxer declared her candidacy for mla reference research paper, elective office for describe a process, the first time in 1971. Although her husband was equally well qualified to represent the progressive environmental constituency with which the couple had become involved, he could not afford to sacrifice his lucrative law practice for the $11, 000 annual salary paid to formula, members of the Marin County Board of Supervisors, so Barbara ran, becoming the describe a process essay, first serious female candidate in two decades. Thesis. Although Boxer won a three-way primary race, she ran into serious obstacles in her main campaign, many of which were related to describe a process, her gender. Mla Reference. Even women who worked told her of their doubts that she could care for describe, her young children properly while holding down such a responsible position. In the schools, final election, in November of essay, 1972, Boxer lost by mla reference format a narrow margin. Following this defeat, Boxer re-entered the workforce. Describe A Process Essay. She took a position as a reporter for writing schools, the Pacific Sun, becoming an describe associate editor of the publication from 1972 to 1974. At that time, she returned to the world of politics, as a congressional aide working for the representative from the Fifth Congressional District of apush, California.
Boxer held this post until 1976, when she ran again for the Marin County Board of Supervisors. This time, she was elected. As a Marin County Supervisor, Boxer maintained her strong commitment to the environmental movement. She urged the essay, closure of introductions writing, all nuclear power plants in describe a process, the state of management paper project team, California, and worked for describe a process essay, other liberal causes during her six years in mla reference research, the post. From 1977 to 1982, she served on the Bay Area Air Quality Management Board, of which she was the president from 1979 to describe, 1981. Boxer was also the president of the two kinds paper, Marin County Board of Supervisors from 1980 to 1981. In the early 1980s Boxer's local congressional district, the Sixth District of a process essay, California, was redrawn in c, a manner that helped to insure the re-election of incumbent John L. Burton, a Democrat.
When Burton, a longtime friend and a process essay mentor of Boxer, chose instead to retire, Boxer ran for outline c, the seat he was vacating in describe essay, the U.S. House of management paper team, Representatives. She won the 1982 election as a Democrat. Boxer took office in Washington as a freshman representative at the start of a process essay, 1983, and introductions essay became president of the Democratic New Members Caucus of the describe, House of Representatives. Management Project. The district Boxer went on to represent for describe a process, five terms, covering ten years, included parts of the argumentative model, city of San Francisco, as well as Marin County, her home base. In Congress, Boxer continued to describe, champion the introductions, liberal causes that had brought her popularity with the constituents of this area in describe a process essay, the past.
Boxer was assigned to sit on the Armed Service Committee, where she was one of the few committed liberal members, and became co-chair of the on duty in the, Military Reform Caucus. Boxer was also appointed to a process essay, the Select Committee on two kinds paper Children, Youth, and Families. In addition, she chaired the subcommittee on government activities. In Congress Boxer made a name for herself as a staunch opponent of defense spending. Describe Essay. She opposed the costs of stealth aircraft and the Patriot missile, pushing repeated floor amendments in the house to cut government spending for mla reference research, these projects. Boxer also voted against funding for describe a process, the Nicaraguan contras. In addition, she lent support to apush formula, the Congressional Black Caucus in its recommendation that the a process essay, defense budget be cut in half. Writing. Boxer became best known as a representative for describe, publicizing particularly egregious cases of wasteful military spending. Posing for photographers with a $7, 622 coffee pot for team, a cargo plane, and a $600 toilet seat cover, she dramatized the issue of describe, government excess, bringing public pressure to bear on efforts to reform government procurement. As a result of essays on pivotal, these efforts, Boxer was able to take partial credit for a series of military procurement reform amendments, which included a 1988 measure to protect whistle-blowers, and a measure to allow competitive bidding for essay, contracts to provide spare parts to issues in contemporary, the military.
Despite her best efforts, however, Boxer was unable to describe, keep the management paper project term, Presidio, a historical military base in San Francisco, off the list of military bases to eventually be closed. A Process. Boxer opposed the entry of the essays, United States into the Persian Gulf war in essay, 1991, and she sponsored an mla reference format research effort that would have required prior Congressional approval of covert American actions in foreign countries. This resolution, which was seen a threat to the secrecy of war plans and anti-terrorist operations, was unanimously defeated on describe the floor of the in the military, House, as even Boxer withdrew her support for describe a process essay, the amendment. Apush. As a representative Boxer also maintained her commitment to women's issues. She was an essay original co-sponsor of the Family and Medical Leave Act benefitting workers with children or other family responsibilities, and she put up a strong opposition to the gag rule forbidding abortion counseling at federally funded health clinics. As a supporter of the Freedom of mla reference, Choice Act, Boxer sponsored an amendment to provide federal funding for abortions in a process, cases of rape or incest, which was passed, but vetoed by President George Bush. Creative Writing. Boxer won the a process, respect of the powerful former chairman of the House Ways and two kinds amy tan Means Committee, Dan Rostenkowski, in her fight to pass this bill, with her forthright appeal for his support of the abortion amendment. Describe A Process. Boxer also pursued a campaign to open up the men's club of Congress to greater participation by argumentative outline c women. As part of this effort, she tried to win more extensive locker room facilities for describe a process, female representatives, inspiring an mla reference format research paper apocryphal story about her presence in a process essay, the men's locker room at an inopportune moment. The most important moment in her struggle to instill greater equality for on pivotal, women in the U.S. Congress, however, came during hearings to consider Clarence Thomas for a seat on the U.S.
Supreme Court, when Boxer joined with other female representatives to a process essay, bring their concerns about the treatment of on duty military, Anita Hill to the attention of members of the Senate Judiciary Committee. The group of women was refused entrance to a process essay, a meeting of apush thesis, this committee, after being told that strangers were not permitted in the room. Boxer was so incensed by essay the idea that she and the other female representatives were considered strangers in essay model c, the Senate that she later wrote a book using this phrase as its title, describing the progress of women in politics in her lifetime. The treatment of Hill at the Senate hearings proved to be a political watershed, and when California Senator Alan Cranston announced that he would relinquish his seat after being tainted in a savings and loan scandal, Boxer decided to give up her secure Congressional berth and describe a process run for paper, the Senate as a long-shot candidate in describe a process, 1992. She made the lack of female representation in the U.S. Mla Reference Format Research. Senate a cornerstone of her campaign. A Process. Boxer's first obstacle in her campaign for the Senate was a tough primary, with two strong male contenders who also had solid records on women's rights.
With a strong fund-raising operation in place, as well as the creative, support of groups such as EMILY's List, and the Hollywood Women's Political Committee, Boxer raised more than $2 million by describe the start of management team term, 1992, which allowed her to describe a process, triumph in on pivotal issues, the June primary. Describe Essay. Boxer then went on thesis formula to face Bruce Herschensohn, a conservative television commentator, in the general election. Describe A Process. Despite her ten-year Congressional career, she cast herself as a Washington outsider, whose gender made her a gadfly to the establishment. This picture was somewhat damaged by the revelation during the campaign that she had bounced 143 checks at the U.S. House of essay, Representatives bank. Despite this setback, Boxer relied on her ability to identify issues that voters cared about, and get her position across in a punchy and appealing manner. In a year in which more women than ever before were elected to the Senate, Boxer won her race in November of 1992, becoming, along with Dianne Feinstein, one of two women to a process, make up the California delegation.
As a senator Boxer has continued to push the argumentative model c, liberal agenda she supported as a representative, and a process she has remained sensitive to schools, issues of describe a process essay, importance to apush thesis, women. She joined the effort to pressure Senator Bob Packwood, under fire for sexual harassment, to fully disclose his actions, and describe essay she mounted a campaign, with the other five women in the Senate, to punish a Navy admiral for introductions, the Tailhook sex scandal. Boxer has worked for increased funding for a process essay, breast cancer research and domestic violence programs. Apush Formula. She also staunchly supported an essay openly gay San Francisco woman for a job at the Department of Health and format Human Services, and describe she fought to mla reference format research paper, end restrictions on a process essay gays in essays on duty military, the military. In addition, Boxer has remained true to her roots in the environmental movement. She is on essay the Committee on Environment and Public Works and belongs to three of its subcomittees.
She battled a plan to in the, place a radioactive dump in the California desert and pushed for the restoration of ten wetlands areas in a process essay, California. Boxer has also worked hard to restore the ailing economy of her home state. Two Kinds. In the describe, name of introductions essay, California jobs, she endorsed a controversial proposal to deploy National Guard troops along the a process essay, Mexican border to cut down on illegal immigration. Research Paper. She also supported a move to describe essay, give members of the agricultural industry more time to renegotiate federal water contracts. Apush. As the describe a process essay, ranking member of the Subcommittee on management paper International Finance, Boxer promotes America's competitiveness in today's global economy by lowering trade barriers and expanding exports. In support of her pro-choice stance, Boxer cosponsored the Freedom of describe a process, Choice Act and pushed for argumentative outline c, passage of describe a process, both the Freedom of Access to issues in contemporary, Clinic Entrances Act and the Family Medical Leave Act. In an essay effort to essays on duty military, keep in describe essay, touch with the constituents of top 10, her vast state, Boxer began inviting voters to write to her, and she was soon receiving more mail than any other senator. This outpouring suggests that Boxer has done an effective job of reaching out to the voters of California. Describe Essay. Boxer appears to be laying the groundwork for a long career in the Senate, capping her evolution into schools an effective feminist and liberal politician.
California Journal, April 1, 1992; June 1, 1994. Ms., March/April 1992, p. Describe A Process Essay. 86. National Review, October 19, 1992, p. 21. Essay C. New York Times, October 25, 1993, p. A15. Describe. Additional information was obtained from Senator Boxer's Home Page on outline the Internet. Words near Barbara Boxer in the dictionary. Essay. Create and save customized word lists. Sign up today and top 10 creative schools start improving your vocabulary!
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Smalls-Mantey, Sample F31 Application and Summary Statement. We are truly indebted to the grantee who allowed us to post this outstanding F31 sample application to help the next generation of essay investigators write applications. The F31 sample application below doesn’t reflect the complex layouts of the actual SF 424 PDF forms. Instead, we’ve provided a list of introductions writing key fields from those forms and describe essay the applicant’s responses. Apush Thesis? In addition, we redacted some applicant-specific information such as contact information, publications in press, and budget specifics. The text of describe essay this application is copyrighted. You may use it only for nonprofit educational purposes provided the essay outline model document remains unchanged and the PI, the grantee organization, and NIAID are credited.
Questions? Contact [email protected] We also offer other outstanding Sample Applications. [Our Web version of this sample application can't reproduce the layout of the describe a process essay actual PDF forms. Here is the outline summary that eRA Commons generated at a process, the start of the thesis formula sample app, which reflects many key fields from that form.] Project/Performance Site Locations. [Our Web version of this sample application can't reproduce the layout of the actual PDF forms.
Performance sites are in describe a process essay New York, Maryland, and the United Kingdom.] Research Related Other Project Information. [Our Web version of writing this sample application can't reproduce the layout of the actual PDF forms. Here are the key fields from that form and essay the applicant's responses.] Understanding the basis of an immune response that controls infection or provides sterilizing immunity remains a major goal in the search for effective vaccines or immunotherapies for HIV. Formula? Antibodies (Abs) induced by candidate vaccines to the surface envelope glycoprotein have not neutralized a broad array of primary virus isolates. For this reason, eliciting a cytotoxic cellular response has been the primary goal in most recent vaccine trials. However, this approach has not been successful in containing viral replication in vaccinees that have become HIV-infected. Antibody-dependant cellular cytotoxicity (ADCC) has been shown to mediate sterilizing immunity against challenge with pathogenic simian immunodeficiency virus [Hessel 2007].
In ADCC, Fc-bearing Abs bind viral epitopes coating an infected CD4+ target T cell and an Fc receptor bearing effector, most commonly natural killer cells (NKs), bind the Ab and use perforin to describe essay deliver granzymes which induce apoptosis in the target. We want to study ADCC in infected patients to argumentative essay c understand the magnitude and describe essay characteristics of the best responses achieved by natural infection. First, we will compare ADCC mediated by the sera of a cohort of patients using a granzyme B cytotoxicity assay developed in our lab. Based on these findings, we will select the sera of patients with the two kinds amy tan paper most ADCC, generate monoclonal Abs (mAbs), and a process essay characterize the mAbs based on epitope specificity, affinity, potency, breadth, IgG isotype, and Fc type. We will also evaluate whether ADCC is disparate from two kinds amy tan paper classical neutralization. Describe A Process Essay? Finally, we will use microscopy to examine the synapse between effectors, Abs, and targets. The outcome of this research will provide insight into the characteristics of Abs that mediate ADCC that are likely important goals in the design of HIV vaccines or immunotherapies. Hypothesis: Antibody-dependent cellular cytotoxicity (ADCC) is a function that has been shown to mediate protection from lentiviral infection. We hypothesize that variations in ADCC activity of formula sera are dictated by the amount, specificity, and a process subclass of mla reference HIV-specific antibodies. Aim 1 : Characterize the potency of sera of HIV-infected individuals in essay ADCC.
Aim 2 : Characterize the specificity and mla reference research breadth of antibodies with ADCC activity. Aim 3 : Characterize the structure and describe a process function of the military target-effector synapse using both fixed and live cell laser scanning confocal microscopy (LSCM), transmission electron microscopy (TEM) and describe cryo-electron microscopy (cryo-EM) and tomography. Understanding the role of antibody-dependent cellular cytotoxicity (ADCC) in HIV could provide important insights for induction of this activity through vaccination. This project seeks to characterize the Abs that mediate ADCC and image the functional synapse formed by cellular components involved in formula ADCC with the describe essay goal of defining new goals for the development of HIV vaccines and therapeutics. Gallo RC, Salahuddin SZ, Popovic M. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from on duty in the military patients with AIDS and at risk for AIDS. Describe A Process? Science.
1984; 224: 500-3. Barre-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983; 220(4599): 868-71.
Organization WH. Global summary of the AIDS epidemic, December 2007. Writing? 2007 [cited 2009 September 18, 2009]; Hessell AJ, Hangartner L, Hunter M, Havenith CE, Beurskens FJ, Bakker JM, et al. Fc receptor but not complement binding is important in antibody protection against HIV. Nature. 2007; 449(7158): 101-4. Describe Essay? www.hivresearh.org.
RV144 Phase III HIV Vaccine Trial Press Release. Paper? 2009. Chung A, Rollman E, Johansson S, Kent SJ, Stratov I. The utility of ADCC responses in HIV infection. Describe Essay? Current HIV research. 2008; 6(6): 515-9. Kohl S, Starr SE, oleske JM, Shore SL, Ashman RB, Nahmias AJ. Human monocytemacrophage- mediated antibody-dependent cytotoxicity to herpes simplex virus-infected cells.
J Immunol. 1977; 118(3): 729-35. Paper? Forthal DN, Landucci G. A Process Essay? In vitro reduction of virus infectivity by antibody-dependent cellmediated immunity. Journal of immunological methods. 1998; 220(1-2): 129-38. Stratov I, Chung A, Kent SJ. Robust NK cell-mediated human immunodeficiency virus (HIV)-specific antibody-dependent responses in HIV-infected subjects. Formula? J Virol.
2008; 82(11): 5450-9. Gomez-Roman VR, Florese RH, Patterson LJ, Peng B, Venzon D, Aldrich K, et al. Describe A Process Essay? A simplified method for the rapid fluorometric assessment of antibody-dependent cell-mediated cytotoxicity. Journal of immunological methods. 2006; 308(1-2): 53-67. Migueles SA, Osborne CM, Royce C, Compton AA, Joshi RP, Weeks KA, et al. Lytic granule loading of CD8+ T cells is required for HIV-infected cell elimination associated with immune control. Immunity. 2008; 29(6): 1009-21.
Vago L, Perna SK, Zanussi M, Mazzi B, Barlassina C, Stanghellini MT, et al. Outline Model? Loss of mismatched HLA in leukemia after stem-cell transplantation. N Engl J Med. 2009; 361(5): 478- 88. Essay? Ziegner U, Campbell D, Weinhold K, Frank I, Rutstein R, Starr SE. Deficient antibodydependent cellular cytotoxicity against human immunodeficiency virus (HIV)-expressing target cells in perinatal HIV infection. Clin Diagn Lab Immunol. 1999; 6(5): 718-24. Brunetta E, Fogli M, Varchetta S, Bozzo L, Hudspeth KL, Marcenaro E, et al.
The decreased expression of Siglec-7 represents an apush early marker of dysfunctional natural killer cell subsets associated with high levels of HIV-1 viremia. Blood. 2009. Ljunggren HG, Ohlen C, Hoglund P, Yamasaki T, Klein G, Karre K. Afferent and efferent cellular interactions in natural resistance directed against MHC class I deficient tumor grafts. Describe A Process Essay? J Immunol.
1988; 140(2): 671-8. Essay? De Maria A, Ferraris A, Guastella M, Pilia S, Cantoni C, Polero L, et al. Describe? Expression of HLA class I-specific inhibitory natural killer cell receptors in HIV-specific cytolytic T lymphocytes: impairment of paper specific cytolytic functions. Proceedings of the National Academy of Sciences of the United States of America. 1997; 94(19): 10285-8.
Ahmad R, Sindhu ST, Toma E, Morisset R, Vincelette J, Menezes J, et al. Evidence for describe, a correlation between antibody-dependent cellular cytotoxicity-mediating anti-HIV-1 antibodies and prognostic predictors of HIV infection. In The? J Clin Immunol. 2001; 21(3): 227-33. Lambotte O, Ferrari G, Moog C, Yates NL, Liao HX, Parks RJ, et al. Heterogeneous neutralizing antibody and describe essay antibody-dependent cell cytotoxicity responses in HIV-1 elite controllers. AIDS. 2009; 23(8): 897-906. Dalgleish A, Sinclair A, Steel M, Beatson D, Ludlam C, Habeshaw J. Introductions Writing? Failure of a process ADCC to predict HIV-associated disease progression or outcome in a haemophiliac cohort. Clin Exp Immunol. Essay? 1990; 81(1): 5-10.
Koup RA, Sullivan JL, Levine PH, Brewster F, Mahr A, Mazzara G, et al. Describe A Process? Antigenic specificity of essay writing antibody-dependent cell-mediated cytotoxicity directed against human immunodeficiency virus in antibody-positive sera. Essay? J Virol. Writing? 1989; 63(2): 584-90. Doria-Rose NA, Connors M. Antibody-secreting B cells in HIV infection. Curr Opin HIV AIDS. 2009; 4(5): 426-30. Burke B, Barnett SW.
Broadening our view of protective antibody responses against HIV. Current HIV research. Essay? 2007; 5(6): 625-41. Sattentau Q. Avoiding the void: cell-to-cell spread of human viruses. Apush Formula? Nat Rev Microbiol. 2008; 6(11): 815-26.
Chamow SM, Zhang DZ, Tan XY, Mhatre SM, Marsters SA, Peers DH, et al. A humanized, bispecific immunoadhesin-antibody that retargets CD3+ effectors to kill HIV-1- infected cells. J Immunol. Describe A Process Essay? 1994; 153(9): 4268-80. Jolly C, Kashefi K, Hollinshead M, Sattentau QJ. HIV-1 cell to cell transfer across an Env-induced, actin-dependent synapse.
J Exp Med. Writing? 2004; 199(2): 283-93. Groot F, Welsch S, Sattentau QJ. Efficient HIV-1 transmission from macrophages to T cells across transient virological synapses. Blood. A Process? 2008; 111(9): 4660-3. Martin N, Welsch S, Jolly C, Briggs JA, Vaux D, Sattentau QJ. Virological synapsemediated spread of formula human immunodeficiency virus type 1 between T cells is a process essay sensitive to formula entry inhibition. J Virol. 2010; 84(7): 3516-27.
Intellectual Support : My mentors Mark Connors and a process Quentin Sattentau are leading experts in their field and apush thesis have mentored numerous people that have gone on to successful careers in describe essay science. Research Paper? This dual mentorship will teach me to aggressively approach science from two distinctive perspectives in my graduate career, something most PhD scientist don’t experience until their first post-doctoral experience. While at NIH I will have received extensive support of staff from Richard Siegel, Director of the NIH MD/PhD partnership program and Michael Lenardo, Director the NIH/Oxford/Cambridge Scholars Program. While at Oxford I will have the guidance of Lucinda Risius, Managing Director of the Graduate Pathology Program and I will also be assigned a departmental advisor, outside of my lab, with whom I can discuss my research Progress. Educational Resources : Through the FAES at NIH I have access to courses to improve lab specific skills and foundation knowledge. Describe A Process Essay? I have already participated a Vaccine Development course. At Oxford I will take seminars at the Centre for in the, Excellence in Teaching and Learning for training in teaching skills. I will also take courses pertinent to my research offered at the Dunn School of Pathology. Both the NIH and describe Oxford have libraries and IT staff that can aid me in scholarly research. Physical Resources : Both labs have sufficient funding to provided me any reagent/equipement need for the proposed research. Lab Space – I am provided with a desk and format personal desktop computer.
Bench space is shared within the lab. Safety – In order to ensure our safety from essay hazardous blood samples we work under laminar flow hoods in a P2 facility with P3 practices. Samples – We receive blood samples from top 10 creative writing patients enrolled within our protocol. We also have access to a process the NIH blood blank for normal human blood samples. As provided by Quentin Sattentau: “Oxford University is held in high international regard for its strong teaching and research background and its unique and personal teaching style. Essays On Duty? Within the University the Department of Pathology has an excellent reputation for graduate teaching, and has achieved 100% success in DPhil graduation within 4 years for the past 3 years.
The Department has a strong graduate support structure, in which each student has a principal supervisor, the essay possibility of a cosupervisor, a departmental advisor, and a college advisor. The supervisor(s) will generally meet with the student multiple times a term, and each of the non-supervisory mentors will meet with the candidate approximately once a term and will file reports on the candidate’s progress. The candidate will be expected to attend a series of high profile external seminars that take place once a week in term time, and introductions essay a regular series of internal seminars from leading and describe essay more junior University and Departmental investigators and students. Adjoa will attend and argumentative essay model participate in the weekly lab journal club, in which scientific papers are taken apart critically by a process, members of the group, and a weekly laboratory meeting in which each lab member presents their ongoing research. Adjoa will also be encouraged to essay chat to other members of the department during tea lunch and coffee breaks, a longstanding Oxford institution! The Department has a fully equipped quiet library for describe a process, literature research and other reading and writing. Adjoa will have her own writing up space close to her work bench, equipped with a portable computer and if required, an external screen. Adjoa will have full access to apush all core facilities, including the a process imaging suite with multiple light microscopes, a flow cytometry and sorting suite, an electron microscopy facility with full technical and research scientific support. We also have strong connections with the biochemistry and chemistry departments and the Weatherall Institute of essay Molecular Medicine at the John Radcliffe Hospital for obtaining clinical samples and expertise.”
BD FACSAria IIu. BD Pathways 855. VICTOR Light luminescence plate reader. AutoMACS Pro Separator. AutoMACS Classic Separator. Containment II/III Laboratory with 4 tissue culture hoods. Tissue culture. The laboratory has a new tissue culture facility comprised of 8 double hoods and apush formula associated incubators and ancillary equipment that is shared with three other virology groups. Virology. The department has a large, fully-equipped containment-III laboratory shared between two groups, with three tissue culture hoods and associated incubators and ancillary equipment, in which HIV-1 is grown and describe essay used to infect cells.
Flow cytometry. The department has a core flow cytometry facility with three BD analyzers (2 x FACScalibur 2 x LSR2) and two sorters. Molecular biology. The Sattentau laboratory has all facilities for molecular biology carried out under containment levels –I, -II and –III. Light microscopy. The department has 5 confocal microscopes of format paper varying sophistication and resolution, two of which are set up for live cell immunofluorescence work. The department has three recently acquired high-speed CCD cameras and associated microscopes for live cell immunofluorescence analysis.
The Sattentau laboratory has a Zeiss Pascal confocal microscope and describe essay a new CCD camera set up with a Zeiss Axiovert 200 microscope for fixed and live cell work in the containment-III laboratory, allowing real time analysis of live, infected cells. Electron microscopy. The department has two transmission electron microscopes and a scanning electron microscope, all of on duty military which are maintained and run as a central service facility by a skilled dedicated operator. Our collaborator in a process Oxford (Kay Grunewald) is essays on duty in the military located at the University Churchill campus, which is 4 miles from the Pathology Department. A Process Essay? He maintains and uses 3 microscopes set up for cryo-tomography as follows. 300keV FEG cryo-electron microscope FEI TF30 Helium Polara with GIF2002 imaging filter (2 x 2k CCD) 300keV FEG cryo-electron microscope FEI TF30 with 4 x 4kCCD 120keV cryo-electron microscope FEI T12 with 4 x 4k CCD. Research Related Senior/Key Person Profile.
[Our Web version of this sample application can't reproduce the layout of the actual PDF forms. See below for the biographical sketch attachments.] My interest in studying infectious diseases stems from the 2001 anthrax scare in the Washington D.C. area. Top 10 Creative? I already had a strong interest in science but through my participation in the Gene Search Science Project at Catholic University the following summer I came to understand how medical research impacts treatment for routine illnesses and also plays a role in national defense. Since middle school I have been preparing for describe a process essay, a career in formula science. Essay? At Eleanor Roosevelt High School I was enrolled in the rigorous Science and Technology Program during which time in participated in the Gene Search Project and researched biochemical pathways that influence sickle cell anemia with Dr. William Winters at Howard University Hospital. This experience taught me how research and creative schools medicine are intertwined and inspired me to essay become a physicianscientist. At UMBC I was a member of the Meyerhoff Scholars Program and an HHMI Undergraduate Research Scholar where numerous lab experiences, seminars, rigorous classes, and essays on duty military multiple opportunities for scientific presentations prepared me for a process, a career as a scientist.
My lab skills and understanding of a research career increased exponentially during my four years in in the Michael Summers’ lab. Not only describe a process essay did I learn about military protein purification, gel electrophoresis, NMR, and ITC while studying MuLV RNA packaging, but more importantly of the time and describe a process discipline necessary for excellent research and mla reference research the internal drive that keeps one focused. Working with Dr. Nikola Pavletich I learned the value of immediately organizing my data so that others could analyze my results quickly. In the lab of Tom Cech I had the responsibility of designing a new protocol to study telomerase assembly, a skill that has enabled me to design a novel assay to investigate AIDS specific questions in a process essay my graduate studies. Apush Formula? The medical education I’ve received at Columbia has given me a unique perspective with which I approach scientific questions. Under the tutelage of describe a process Mark Connors and Quentin Sattentau, leaders in their fields on nonprogressive HIV infection and introductions viral transmission, my understanding of infectious disease and my capacity to pursue further research in these fields will be greatly enhanced. In addition, the courses, medical preceptorships, presentations, teaching, and career development activities I am undertaking in the forthcoming years make me an a process essay excellent P.I. for two kinds amy tan research, this grant. Academic and Professional Honors. 2003 National Urban League Scholarship 2003 UMBC Meyerhoff Scholar 2003 UMBC Honors College 2003 HHMI Undergraduate Research Scholar 2004 NAD Distinguished Youth Award 2005 UMBC Minority Access to Research Careers Scholar 2005 Abby Rockefeller Mauze Award Charitable Trust Scholar for essay, Outstanding Achievement 2006 Goldwater Scholar 2007 UMBC Top Senior Biochemistry Major 2007 Graduated Sum Cum Laude from UMBC 2007 NIH/Oxford/Cambridge Scholar 2010 International AIDS Vaccine Conference Scholarship 2011 Keystone Symposia Underrepresented Minority Scholarship.
2004 Omicron Delta Kappa Leadership Honor Society 2004 Golden Key International Honor Society, Sophomore/Alumni Director 2007 Phi Beta Kappa. Dey A, York D, Smalls-Mantey A, Summers MF. Writing? 2005. Composition and sequence-dependent binding of RNA to describe a process essay the nucleocapsid protein of introductions writing Moloney murine leukemia virus. Biochemistry. A Process? 44(10), 3735-3744. Miyazaki Y, Irobalieva RN, Tolbert BS, Smalls-Mantey A, Iyalla K, Loeliger K, D'Souza V, Khant H, Schmid MF, Garcia EL, Telesnitsky A, Chiu W, Summers MF. 2010. Structure of a conserved retroviral RNA packaging element by NMR spectroscopy and cryo-electron tomography.
J Mol Biol. 404(5), 751-772. Smalls-Mantey A, Winter W. 2003. Biosynthesis of 2,3-diphosphoglycerate in Erythrocytes. Poster presentation at ERHS Science Fair and Prince Georges County Science Fair. Introductions Essay Writing? March 2003. Smalls-Mantey A, Dey, A, Phillip C, Summers MF. 2004. Describe A Process Essay? Characterization of High-Affinity Nucleocapsid Protein Binding Sites Within the Moloney Murine Leukemia Virus RNA Packaging Signal.
Poster presented at 2004 Annual Biomedical Research Conference for Minority Students, November 2004. Smalls-Mantey A, Min J, Pavletich N. 2005. Structural and Biochemical Studies of the essays on duty Yeast Rad4-Rad23 Complex Bound to describe a process DNA. Poster presented at Tri-Institutional Gateways to the Laboratory Program Symposium and top 10 creative writing schools 2005 Leadership Alliance. Describe A Process Essay? August 2005. Smalls-Mantey A, Miyazaki Y, Summers MF. 2007.
Dimerization of Moloney Murine Leukemia Virus Nucleocapsid Protein Binding Sites Facilitates Binding. Poster presented at 2007 UMBC Undergraduate Research and Creative Achievement Day. Argumentative Outline C? April 2007. Essay? Smalls-Mantey A, Klein R, Doria-Rose N, Laub L, Rood J, Migueles S, Sattenatu. 2010.
HIV-Specific Antibodies Mediate Rapid Antibody-Dependent Cellular Cytotoxicity Against Primary HIV-Infected CD4+ T Cells. Format? Poster presented at 2010 Keystone HIV Vaccines (X5) Meeting. March 2010. Smalls-Mantey A, Klein R, Doria-Rose N, Laub L, Rood J, Migueles S, Sattenatu. 2010. HIV-Specific Antibodies Mediate Rapid Antibody-Dependent Cellular Cytotoxicity Against Primary HIV-Infected CD4+ T Cells. Poster presented at describe essay, 2010 Oxford Pathology Department Graduate Student Symposium. June 2010. Smalls-Mantey A, Klein R, Doria-Rose N, Laub L, Rood J, Migueles S, Sattenatu. Mla Reference Format Research Paper? 2010. HIV-Specific Antibodies Mediate Rapid Antibody-Dependent Cellular Cytotoxicity Against Primary HIV-Infected CD4+ T Cells.
Poster presented at 2010 NIH/Oxford/Cambridge Scholars Research Colloquium. Smalls-Mantey A, Klein R, Doria-Rose N, Laub L, Rood J, Migueles S, Sattenatu. 2010. HIV-Specific Antibodies Mediate Rapid Antibody-Dependent Cellular Cytotoxicity Against Primary HIV-Infected CD4+ T Cells. Poster presented at 2010 International AIDS Vaccine Conference.
September 2010. Smalls-Mantey A. A Process Essay? 2010. Essay Writing? Antibody-Dependent Cellular Cytotoxicity and the Control of HIV. Talk given at Frontiers in Biomedicine NIH/Oxford/Cambridge Scholars Program student presentation series. November 2010. [Outside research support redacted from sample.] A. Personal Statement Regarding Project. Currently HIV-specific ADCC is considered one of the very top priorities in the field of HIV-specific immunity.
Our laboratory has assembled the best techniques and describe essay reagents in the field to carry out this project. We have extensive experience in HIV-specific antibodies and cytotoxicity. Paper? In addition we have a long track record of training students to prepare them for a carreer in biomedical research. 1985 - 1986 Intern in Pediatrics, The Boston Floating Hospital, New England Medical Center, Boston, Massachusetts 1986 - 1988 Resident in Pediatrics, The Boston Floating Hospital, New England Medical Center, Boston, Massachusetts 1988 – 1989 Chief Resident in Pediatrics, The Boston Floating Hospital, New England Medical Center, Boston, Massachusetts July 1989 - October 1989 Medical Staff Fellow, Respiratory Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and a process Infectious Diseases, National Institutes of Health, Bethesda, MD October 1989 - June 1993 U.S. On Duty In The? Public Health Service, Research Associate (C.O.), Respiratory Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of describe essay Health, Bethesda, MD July 1993 - June 1994 U.S. Public Health Service, Clinical Associate, Clinical Center, National Institute of introductions essay writing Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD January 1994 - June 1994 Clinical Fellow in Infectious Diseases, The Childrens Hospital of Philadelphia, Philadelphia, PA. June 1994 - December 2004 U.S. Public Health Service, Medical Officer, National Institute of Allergy and Infectious Diseases, Clinical and Molecular Retrovirology Section, Laboratory of Immunoregulation, National Institutes of Health, Bethesda, MD December 2007- Present Chief, HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. Recent Honors and Editorial and Review Board Activities.
2009 - U.S. A Process? Public Health Service Outstanding Service Medal 2009 - present Vaccine Production Development Team Scientific Advisory Board, University of writing Pennsylvania 2009 - present HIV Enterprise Host Genetics and HIV Diversity Working Group 2010 - present Editorial Board, Journal of Virology. C. Peer-Reviewed Publications. Migueles SA, Sabbaghian MS, Shupert WL, Bettinotti MP, Marincola FM, Schwartz D, Sullivan J, and describe a process Connors M. HLA B*5701 is highly associated with restriction of virus replication in a subgroup of apush HIV infected long term nonprogressors. PNAS 2000; 97(6): 2709-2714. Migueles SA, Laborico AC, Shupert WL, Sabbaghian MS, Rabin R, Hallahan C, Van Baarle D, Kostense S, Miedema F, McLaughlin M, Ehler L, Metcalf J, Liu S, and Connors M. A Process? HIV-specific CD8+ T cell proliferation is essay writing coupled to perforin expression and is maintained in essay nonprogressors. Nature Immunol 2002; 3(11); 1061-1068.
Migueles SA, Laborico AC, Imamichi H, Shupert WL, Royce C, McLaughlin M, Ehler L, Metcalf J, Liu S, Hallahan CW, and Connors M. The differential ability of creative writing schools HLA B*5701+ long-term nonprogressors and progressors to restrict HIV replication is a process not caused by loss of essay outline model c recognition of describe a process essay autologous viral gag sequences. J Virol 2003; 77(12); 6889-6898. Iyasere C, Tilton JC, Johnson AJ, Younes S, Yassine-Diab B, Sekaly RP, Kwok WW, Migueles SA, Laborico AC, Shupert WL, Hallahan CW, Davey RT Jr., Dybul M, Vogel S, Metcalf J, and Connors M. Diminished proliferation of HIV-specific CD4+ T Cells is associated with diminished IL-2 production and argumentative outline model c recovered by describe, exogenous IL-2. J Virol 2003; 77(20); 10900-10909. Tilton JC, Luskin MR, Johnson AJ, Manion M, Hallahan CW, Metcalf JA, McLaughlin M, Davey RT Jr., and Connors M. Changes in paracrine IL-2 requirement, CCR7 expression, frequency, and cytokine secretion, of HIV-specific CD4+ T cells are a consequence of antigen load. J Virol 2007; 81;2713-2725.
Migueles SA, Osborne CM, Royce C, Compton AA, Joshi RP, Weeks KA, Rood JE, Berkley AM, Sacha JB, Cogliano-Shutta NA, Lloyd M, Roby G, Kwan R, McLaughlin M, Stallings S, Rehm C, O’Shea MA, Mican J, Packard B, Komoriya A, Palmer S, Wiegand AP, Maldarelli F, Coffin JM, Mellors JW, Hallahan CW, Follman DA and Connors M. Format Paper? Lytic Granule Loading of CD8+ T-Cells is Required for HIV-Infected Cell Elimination Associated with Immune Control. Describe A Process Essay? Immunity 2008; 29 (6): 1009-1021. Migueles SA, Weeks KA, Nou E, Berkley AM, Rood JE, Osborne CM, Hallahan CW, Cogliano-Shutta NA, Metcalf JA, McLaughlin M, Kwan R, Mican JM, Davey RT Jr, Connors M. Defective human immunodeficiency virus-specific CD8+ T-cell polyfunctionality, proliferation, and thesis formula cytotoxicity are not restored by antiretroviral therapy. J Virol 2009 83(22): 11876-11889. Doria-Rose NA, Klein R, Daniels M, O'Dell S, Nason M, Lapedes A, Bhattacharya T, Migueles S, Wyatt RT, Korber BT, Mascola JR, Connors M. Breadth of HIV-Specific neutralizing activity in sera: clustering analysis and association with clinical variables. J Virol 2009 84(3): 1631-1636.
Doria-Rose NA and Connors M. Antibody-secreting B cells in HIV infection. Curr Opin HIV AIDS 2009 4:426-430 Wu X, Yang ZY, Li Y, Hogerkorp CM, Schief WR, Seaman MS, Zhou T, Schmidt SD, Wu L, Xu L, Longo NS, McKee K, O'Dell S, Louder MK, Wycuff DL, Feng Y, Nason M, Doria-Rose N, Connors M, Kwong PD, Roederer M, Wyatt RT, Nabel GJ and Mascola JR. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 2010 329:856-861. Migueles SA and Connors M. Long-term nonprogressive disease among untreated HIV-infected individuals: clinical implications of understanding immune control of HIV. Describe? JAMA 2010 304:194-201. [Redacted publication in formula press] The research direction of the HIV-Specific Immunity Section of the Laboratory of Immunoregulation is focused upon mechanisms of immunity to HIV. A Process Essay? The laboratory is staffed by PhD and MD scientists with extensive experience in the humoral or cellular immune response to HIV. In addition we have close collaborations with investigators at the NIAID Vaccine Research Center in top 10 the area of structure-function relationships of HIV-specific antibodies.
Our laboratory is well equipped with multi-laser flow cytometers, automated magnetic sorters, and imaging equipment to carry out describe this project. Our laboratory is introductions writing supported by the research budget of the Division of Intramural Research. Over the past 4 years we have received supplemental funding from the Intramural AIDS Targeted Antiretroviral Program (IATAP). This will continue for the next 2 years. We have also received funding from the Office of essay AIDS Research for work on the humoral response to HIV. Positions and Employment.
1985 - 1992 Lecturer, Department of Genito-Urinary Medicine, University College London, UK 1989 - 1991 Visiting scientist, Howard Hughes Medical Institute, Columbia University, New York, NY 1992 - 1998 Staff scientist (Director of Research), Centre d’Immunologie, Marseille, France 1999 - 2003 Reader, Section of on duty in the military Infectious Disease, Imperial College London, London UK 2003 - Professor of immunology, Department of Pathology, University of Oxford, Oxford UK. Other Experience and Professional Memberships. 1995 - Member, American Association for the Advancement of describe a process essay Science 1998 - Member, American Society for Microbiology 1998 - Member, British Society for Immunology, UK 1998 - Member, Society for General Microbiology, UK 2005 - Member of the Pasteur Institute Paris France Scientific Evaluation Committee. 2005 - Member of the essay Vaccine Research Center (VRC) NIH Board of Scientific Councilors 2007 - Member of essay BMGF Vaccine Monitoring Centre SAB 2008 - Member of NIH HIVRAD/Novartis Neutralizing Antibody Vaccine Consortium SAB 2009 - Member of study section for Swedish Program for International Development 2010 - Member of NIH study section for formula, the B cell Immunology Partnership Program for HIV-1 Vaccine Discovery (U19) C. Selected Peer-Reviewed Publications. Most relevant to the current application.
Martin N, Welsch S, Jolly C, Briggs JA, Vaux D and Sattentau QJ. (2010) Virological synapse-mediated spread of human immunodeficiency virus type-1 between T cells is sensitive to a process essay entry inhibition. J. Virol. 84: 3516-3527. Gonzalez N, Bermejo M, Calonge E, Jolly C, Arenzana-Seisdedos F, Pablos JL, Sattentau QJ and Alcami J. Formula? (2010) SDF-1/CXCL12 production by mature dendritic cells inhibits the propagation of X4-tropic HIV-1 isolates at the dendritic cell-T-cell infectious synapse. J Virol. 84:4341-51 Groot F, Welsch S and Sattentau QJ. (2008). A Process? Efficient HIV-1 transmission from macrophages to T cells across transient virological synapses. Blood 111: 4660-4663. Sowinski S, Jolly CJ, Berninghausen O, Purbhoo, MA, Chauveau A, Kohler K, Oddos S, Eissmann P, Brodsky FM, Hopkins C, Onfelt B, Sattentau QJ and Davis DM (2008). Membrane nanotubes physically connect T cells over on duty in the military long distances presenting a novel route for HIV-1 transmission.
Nature Cell. Biol. 10: 211-219. Jolly C and Sattentau QJ (2007). HIV-1 assembly, budding and cell-cell spread in T cells takes place in tetraspanin-enriched plasma membrane. J. Virol.
81:7873-7884 Jolly C and Sattentau QJ (2007). Adhesion molecule interactions facilitate human immunodeficiency virus type-1-induced virological synapse formation between T cells. Describe A Process? J. Essay Writing? Virol. 81: 13916-13921. Jolly C, Mitar I and Sattentau QJ (2007).
Requirement for an intact actin and essay tubulin cytoskeleton for writing, efficient HIV-1 assembly and spread. A Process? J. Virol. 81: 5547-6 Jolly C and Sattentau QJ. Writing Schools? Human Immunodeficiency virus type-1 virological synapse formation in describe a process essay T cells requires lipid raft integrity. Two Kinds Research Paper? J. Virol.
2005 79: 12088-12094. Jolly C, Kashefi K, Hollinshead M and Sattentau QJ (2004) HIV-1 cell-to-cell transfer across an Env-induced, actin-dependent synapse. J. Exp Med. 199: 283-193. Additional recent publications of important to the Field (in chronological order)
Wegmann F, Krashias G, Luhn K, Laamanen K, Vieira S, Jeffs SA, Shattock RJ and Sattentau QJ (2011) A novel strategy for describe essay, inducing enhanced mucosal HIV-1 antibody responses in an anti-inflammatory environment. PlosOne 6: e15861. Kong L, Sheppard N, Stewart-Jones G, Robson CL, Chen H, Xu X, Krashias G, Bonomelli C, Scanlan CN, Kwong PD, Jeffs SA, Jones IM, Sattentau QJ (2010) Expression system-dependent modulation of writing HIV-1 envelope glycoprotein antigenicity and immunogenicity. Describe? J. Mol. Biol. Aug 25th epub. Krashias G, Simon K, Wegmann F, Kok WL, Ho LP, Stevens D, Skehel J, Heeney JL, Moghaddam AE and Sattentau QJ. (2010). Potent adaptive immune responses induced against outline c HIV-1 gp140 and describe essay influenza virus HA by a polyanionic carbomer.
Vaccine 28: 2482-2489. Zanetti G, Briggs JAG, Grunewald K, Sattentau QJ and Fuller SD. SIV spike glycoprotein structure in two kinds amy tan research paper situ determined by cryo-electron tomography. Describe? Plos Pathogens August 2 (8): e83 Sheppard NC, Bates AC and Sattentau QJ (2007). Model? A functional human IgM response to a process HIV-1 Env after immunization with NYVAC-HIV C. AIDS 19: 524-527. [Outside research support redacted from sample.] PHS Fellowship Supplemental Form, Research Plan. [Our Web version of this sample application can't reproduce the apush thesis formula layout of the actual PDF forms. The attachments are included below. In the original version, these attachments met the page limits.] Understanding the basis of an immune response that controls infection or provides sterilizing immunity remains a major goal in describe the search for effective vaccines or immunotherapies for HIV.
Antibodies (Abs) induced by candidate vaccines to essay writing the surface envelope glycoprotein have not neutralized a broad array of primary virus isolates. For this reason, eliciting a cytotoxic cellular response has been the primary goal in most recent vaccine trials. However, this approach has not been successful in containing viral replication in vaccinees that have become HIV-infected. Antibody-dependant cellular cytotoxicity (ADCC) has been shown to describe a process mediate sterilizing immunity against outline model challenge with pathogenic simian immunodeficiency virus [Hessel 2007]. In ADCC, Fc-bearing Abs bind viral epitopes coating an infected CD4+ target T cell and a process an Fc receptor bearing effector, most commonly natural killer cells (NKs), bind the Ab and introductions writing use perforin to deliver granzymes which induce apoptosis in the target. We want to study ADCC in infected patients to understand the magnitude and characteristics of the best responses achieved by natural infection.
First, we will compare ADCC mediated by describe, the sera of a cohort of patients using a granzyme B cytotoxicity assay developed in our lab. Based on these findings, we will select the sera of patients with the most ADCC, generate monoclonal Abs (mAbs), and characterize the mAbs based on epitope specificity, affinity, potency, breadth, IgG isotype, and introductions writing Fc type. A Process Essay? We will also evaluate whether ADCC is format disparate from classical neutralization. Finally we will use microscopy to examine the synapse between effectors, Abs, and a process essay targets. The outcome of this research will provide insight into the characteristics of essay model c Abs that mediate ADCC that are likely important goals in the design of HIV vaccines or immunotherapies.
Hypothesis: Antibody-dependent cellular cytotoxicity (ADCC) is describe a process essay a function that has been shown to mediate protection from lentiviral infection. We hypothesize that variations in ADCC activity of sera are dictated by the amount, specificity, and subclass of HIV-specific antibodies. Aim 1 : Characterize the potency of top 10 sera of HIV-infected individuals in ADCC. In ADCC, Abs bind viral epitopes that are presented by infected CD4+ T cells. NKs expressing an Fc receptor bind the Fc domain of the Ab and use perforin to deliver granzymes to the HIV-infected cell. Subsequently, granzymes induce apoptosis within the cell. Our lab has developed a flow cytometric assay that measures granzyme B delivered to an HIV-infected CD4+ target T cell. We will classify ADCC by the percent of target cells receiving granzyme and essay the elimination of targets as defined by residual percent of targets expressing p24, HIV capsid. Compare the serum of HIV+ individuals with various rates of formula progression and viral loads to a process essay determine which contain Abs capable of mediating the top 10 writing schools highest levels of ADCC. Compare the ADCC and neutralizing activity of patient sera. Aim 2 : Characterize the specificity and breadth of antibodies with ADCC activity.
Our laboratory has panels of NAbs derived from patients with known serum neutralizing or ADCC-mediating activity. Determine whether recognition of specific epitopes is required for a process essay, ADCC. Essay Outline C? Define the breadth of the a process essay polyclonal sera by its ability to mediate ADCC in CD4+ T cells infected by different clades of HIV. Titer serum total IgG, IgG1, and IgG3 binding infected CD4+ T cells. Aim 3 : Characterize the writing schools structure and function of the a process essay target-effector synapse. Using both fixed and live cell laser scanning confocal microscopy (LSCM), transmission electron microscopy (TEM) and cryo-electron microscopy (cryo-EM) and tomography, we will examine the synapse formed between NK and other cells with potential ADCC activity (macrophages and neutrophils) and infected target cells.
We will specifically investigate: The structure of a functional ADCC synapse. The kinetics of ADCC function in real time and its relation to two kinds amy tan paper antibody type and specificity. A role for antibody-dependent cell-mediated phagocytosis (ADCP) in elimination of HIV-infected cells. d. Receptors and a process essay effector molecules central to ADCC activity against HIV infected cells. Since being identified as the causative agent of AIDS in 1983, HIV infection has reached epidemic proportions with an estimated 2 million people worldwide dying from AIDS each year 1- 3. There is more public awareness about how to prevent HIV infection but with the growing incidence of HIV infection and amy tan research paper the limitations of describe a process current antiretroviral therapy, there is an imperative need for a vaccine.
One of the most critical areas of research on vaccines for HIV is the search for correlates of immunity. At present the only method for determining the potential benefits of a vaccine with regard to protection from introductions infection or lowering of viral load upon infection remains very large clinical efficacy trials. Determining correlates of immunity would tremendously accelerate the development process by permitting some estimation of essay clinical efficacy prior to top 10 creative a Phase III trial. Describe A Process? Reliable correlates would permit screening of vaccine candidates at a much earlier point in development with smaller numbers of participants. Over the past 20 years, research into correlates of immunity to HIV have largely focused on CD8+ cytotoxic T lymphocytes (CTLs) or neutralizing antibodies (NAbs). In addition to essay writing neutralization, antibodies (Abs) may fight viral infections by antibody-dependent cell-mediated phagocytosis (ADCP) or by describe essay, antibody-dependent cellular cytotoxicity (ADCC). In ADCC, Abs bind viral epitopes presented on infected target cells and top 10 schools Fc? receptor-bearing effector cells such as natural killer cells (NKs) recognize and describe essay bind the outline model c Fc? region of these Abs. Upon cross-linking of the Fc? receptor, NKs release perforin that punctures the target’s cell membrane and deliver proteases such as granzyme B (GrB) which induce apoptosis. ADCC has become a major focus within the field following two important studies highlighting its potential importance in providing immunity to describe essay HIV. A recent study by Burton and colleagues demonstrated that neutralizing Abs with mutated Fc? receptor binding regions were less effective in protecting macaques from HIV whereas Abs with impaired complement binding conferred protection to top 10 creative writing schools macaques, suggesting that ADCC may be more important in preventing infection than neutralization or complement activation alone 4. Prior to this study, it was widely accepted that infection of a single cell would lead to a process integration and chronic infection. However, because ADCC mediated effects are on virus infected cells and not free virions, this study provided indirect evidence and proof of the essays on duty concept that ADCC can eliminate lentivirus-infected cells in vivo.
In addition, some recent data in human efficacy trials has also greatly increased interest in ADCC as an important component of describe a process vaccine induced immunity to on duty in the HIV. Describe A Process Essay? In September 2009 data from the phase III RV144 (Thai) vaccine trial were released and showed that the prime-boost combination of ALVACR HIV and AIDSVAXR B/E reduced HIV infection. Two Kinds Amy Tan Research? This vaccine regimen was known to not elicit a strong cellular or NAb response. It does, however, elicit binding antibodies that have suggested to the field that the protective efficacy is likely mediated through ADCC 5. Our laboratory is part of a large international effort to characterize ADCC antibodies from this trial in order to determine whether there were higher ADCC-mediating antibodies in uninfected vaccinees compared to describe essay those that were infected. Although HIV-specific ADCC is now considered an extremely important part of vaccineinduced immunity several basic questions regarding the nature of an effective ADCC response have not been addressed. For example, the argumentative essay model c number, affinity, and specificities of antibodies necessary to mediate ADCC remains poorly understood. Describe A Process? Our laboratory has now developed assays that can accurately measure ADCC against on duty military HIV-infected cells. We also have assembled panels of monoclonal antibodies from individual patients that permit a characterization of describe a process individual antibodies that mediate HIV-specific ADCC. One of the initial goals of this project was to adapt our current killing assay to essays on duty military provide a more robust assay for HIV-specific ADCC. Past studies of ADCC have been hampered by the availability of assays that are only partially quantitative.
There are four primary methods that people use to measure ADCC 6. A Process? The most prevalent is the amy tan research paper chromium release assays (CRA), which is essay highly variable, does not specifically account for amy tan paper, the mechanism of killing, and is insufficiently quantitative 7. The ADCVI assay incubates targets, serum, and describe effectors for 24 hours and the supernatant is applied to the B95-8 cell line for amy tan paper, 5-7 days. The endpoint is reduction of viral infection of the B95-8 cells 8. This method measures inhibition of viral production and a process subsequent infection but its disadvantages lie in the length of the assay and failure to measure killing of infected cells. Another assay is the intracellular cytokine staining ADCC (ICS-ADCC) assay measures IFN-?, the primary cytokine responsible for the antiviral activity of many cells including NKs, CTLs, Th1, and dendritic cells 9. Amy Tan Research Paper? The advantages of describe essay this assay are that multiple effector functions can be measured and all cells and Abs are from the same patient, but it is top 10 creative writing still a proxy that does not measure HIV-infected cell killing. The rapid and fluorometric antibody-dependent cellular cytotoxicity (RFADCC) assay directly measures cell killing but requires whole protein 10. A Process? While use of protein pulsed targets is a sensitive method, it likely places artificially high amounts of protein on the surface of infected cells, potentially overestimating the efficacy of ADCC. Recently our lab has developed a highly quantitative flow cytometric assay to measure GrB cytotoxicity using primary HIV-infected CD4+ T cells as targets and autologous NKs as effectors. This is an essay c adaptation of an a process assay for measuring the cytotoxic activity of CTLs developed in amy tan paper our lab11. This assay measures the cleavage of a GrB substrate, and eliminates background cell death using a Live/Dead stain to essay produce accurate quantitative and highly reproducible results. In brief, CD4+ T cells are stimulated for 3 days and HIV infected.
Autologous, negatively selected NKs are used as effectors. Effectors and targets are labeled with surface dyes so that they can be discriminated. NKs, targets and serum are incubated in the presence of a granzyme cleavable fluorescent substrate. Granzyme delivery to the target cell and elimination of HIV-infected targets can then be measured by flow cytometry (Figure 1). Cellular GrB content.
GrB cleaves GranToxiLux substrate (FITC), indicating the amount of GrB present within a target cell (Pacific Blue). Elimination of HIVSF162-infected cells. Live targets are stained for intracellular HIV capsid, p24 (PE). Some infected cells show downregulation of CD4 (PE-Cy7). A reduction in the number of p24 stained cells is represented as Infected Cell Elimination (ICE) and essay is an indication of cell death. In the example above, ICEInfected+Effectors+Serum = [(58.2-25.8)/58.2] x 100 = 54.9%.
There are several advantages to this assay over older assays that use mismatched cell lines. Because NKs lyse target cells in the context of MHC mismatch and cause nonspecific killing, autologous cells are used in our assay to reduce background. Essay? 12. In addition, because NK function is diminished in HIV-infected patients, we use the NK cells and creative writing CD4+ T cell targets from uninfected patients in our assay as a readout for the effectiveness of a given serum sample in a process essay mediating ADCC 13, 14. We observed variations in NKs from essay model c normal individuals in their ability to mediate ADCC and choose donors that provide optimal signal to noise ratio that we will use to compare the serum of HIV+ individuals (Figure 2). The targets used in this assay are likely closer to a process the in vivo situation given autologous HIV-infected targets are used in creative writing the place of antigen pulsed cell lines. Other advantages include our assay’s ability to measure the describe mechanism of ADCC (granzyme delivery) and the outcome (death of infected cells) (Figure 2). MHC-1 is down-regulated in virally infected cells, and the loss of MHC-mediated killer inhibitory signals permit NKs to amy tan paper kill a cell 15, 16. We control for essay, this by measuring the writing granzyme content of targets that are incubated only with effectors and describe a process sera from HIV-uninfected volunteers. Amy Tan? For a positive control we are using a novel anti-CD3 Ab that will mediate ADCC to describe a process all CD3-bearing targets (Figure 3). Two Kinds Amy Tan Paper? With this Ab we have already demonstrated (1) the sensitivity and dynamic range with which we are able to a process essay measure ADCC, (2) Abs mediate ADCC in a dose dependent manner, and (3) GrB delivery is proportional to cell death.
Aim 1: Characterize the apush thesis formula magnitude of describe essay ADCC in schools HIV infected individuals . Rational : There is considerable controversy regarding the magnitude of ADCC activity in sera from HIV+ individuals and how it correlates with disease progression. It has been suggested that sera from elite controllers exhibit greater ADCC activity which correlates with CD4+ T cell count 17, 18 while others have sighted no correlation between ADCC and disease progression 19, 20.We will compare the serum of HIV+ individuals with various rates of progression and a process viral loads to determine which contain Abs capable of mediating the highest levels of ADCC. We will also compare the ADCC and essay outline model neutralizing activity of patient serum to evaluate whether or not ADCC and describe neutralization always occur together in polyclonal sera which is creative writing schools yet to be determined 21, 22. Methods : Over the past several years, in collaboration with the describe a process essay Vaccine Research Center (VRC) our laboratory has focused upon recruiting HIV-infected patients with broadly crossneutralizing antibodies. We have extensive clinical data and neutralization data for all of the patients. With the data we generate from our ADCC assay we are able to compare multiple indicators of immunity with ADCC.
Expected Outcomes/Interpretation : Based on in vitro and passive transfer macaque studies, we expect LTNPs to exhibit greater ADCC than progressors. Essay Writing? Our current knowledge attributes LTNP delayed progression to superior CTL cytotoxicity but our data may show ADCC also to be a significant factor 11. Potential Complications : We do not foresee any difficulties in describe a process essay accomplishing this objective. Aim 2: Characterize MAb from serum identified as having potent ADCC activity with regard to specificity. Rational/Methods : HIV-infected cells express Envelope (Env) protein on their surface which is recognized by NAbs and argumentative c presumably by ADCC-mediating Abs. We will use standard Nabs (including b12, 2F5, 2G12, 447-52D, 17B, and a process essay VRC01) and patient derived MAbs to writing probe specificities required for describe a process essay, ADCC. An ideal HIV vaccine would be able to protect against mla reference paper diverse virus strains so it is important to determine whether Abs raised against one clade of virus would be able to mediate ADCC in CD4+ T cells infected by different clades. We will use multiple strains of describe virus from clade A/E, B, and C to infect CD+ T cells and mla reference format research compare killing of target cells in the presence of serum pooled from clade B HIV+ patients. IgG1 and IgG3 are the predominant IgG isotypes with roles in ADCC. It is a process possible that variations in ADCC activity of sera are mediated by variations in IgG subclass. We will use infected CD4+ T cells, apply sera with various levels ADCC at the same dilutions used in our killing assay, and measure total bound IgG, IgG1, and IgG3 by flow cytometry.
We believe flow cytometry is a better way of measuring titers of binding Abs as compared to ELISA because Abs will recognize all possible epitopes on the surface of an infected cell in their natural conformation. Expected Outcomes/Interpretation : Determining the association between ADCC activity and IgG subclass may provide insights into the necessity of eliciting a specific class of IgG via particular antigens and adjuvants. Potential Complications : We now have robust assays for subclass binding and do not expect complications with this portion of the project. Aim 3: Evaluation of the target-effector synapse. Rational : Using microscopy to study ADCC is important because it will help us define structural and essay writing kinetic parameters and essay will relate structure to function.
Multiple mechanisms for cell-to-cell spread of HIV have been described but few have described inhibition of viral transmission or targeted cell death 23. Creative? To date there has been no study using microscopy to investigate ADCC in HIV using NKs or macrophages as effectors and CD4+ T cells as targets. In 1994 one group designed a bispecific antibody with anti-CD4 and anti CD3 heavy chains that would redirect CD8+ T cells to kill HIV infected targets 24. With fluorescent microscopy they observed after 1 hour of essay incubation that 24% targets had formed conjugates with CD8+ T cells although many more cells had lysed. At 2 hours 50 - 80% of targets were conjugated and undergoing lysis and by 24 hours all targets had been lysed. However, the bispecific antibody may not be representative of ADCC with naturally occurring HIV-specific antibodies. In addition, the structure of the NK to HIV-infected target synapse was not examined.
Methods : The lab of Quentin Sattentau has focused on examining the synapse of cells involved in HIV infection. They were the first to top 10 demonstrate HIV-1 spread between T cells via virological synapses and nanotube structures for viral transmission between CD4+ T cells 25. They have recently demonstrated that macrophages can infect CD4+ T cells every 6 hours and that cell-tocell transfer of virus is 10-fold more efficient than free virus spread 26. To study the describe a process essay kinetics of ADCC in real time we will use time-lapse laser scanning confocal microscopy (time-lapse LSCM). Cell populations will be negatively selected from mla reference format PBMCs using magnetic cell sorting. HIV-infected CD4+ T cells will be mixed with patient serum or Abs of multiple specificities (see Aim 2) and NKs to evaluate ADCC; or neutrophils/monocytes to evaluate antibody-dependent cell-mediated phagocytosis (ADCP) and applied to describe poly-L-lysine coated cover slips. Cover slips will be fixed in paraformaldehyde, quenched with NH4Cl, permeabilized with Triton-X, and stained for granzyme B, IgG, CD4/CD16/CD14 with fluorescent probes. After mounting, images will be acquired every minute for 6 hours using a Zeiss Pascal Axivert 200M scope. We will use transmission electron microscopy and tomography (TEM) to generate higher resolution static images of the ADCC functional synapse.
For TEM targets, serum, and effectors will be incubated for approximately 1 hour, fixed in paraformaldehyde and glutaraldehyde, and stained with osmium tetroxide. Samples will be embedded in epoxy resin, cut, and imaged using a 300kV FEI Technai TF30 27. If necessary cryo-EM will also be used for structural studies with the aid of Oxford collaborator Kay Grunewald. These experiments will be completed using the pathology department’s core bioimaging facility and I will take department’s Advanced Light Microscopy and outline Electron Microscopy course in preparation for this research. Expected Outcomes : We expect to elucidate the kinetic and functional relationship between ADCC components and answer questions such as what density of Env epitopes are needed to recruit effectors, how many effectors are recruited per target. We do not foresee any difficulties in a process essay accomplishing this objective. The results of essay writing these studies will include novel MAb with possible therapeutic value; a new tool for the study of ADCC with potential utility for a process, HIV vaccine trials; and increased understanding of basic HIV immunology. In the wake of the argumentative essay model RV144 trial, ADCC has become a major focus in the field of describe a process essay HIV-specific immunity. We are very well positioned to carry out these important studies because of our large collection of cells, sera, and detailed clinical data from patients that are part of the NIAID HIV clinic, and argumentative c both labs’ extensive experience in this area. Samples are collected under the describe NIAID IRB-approved protocol 02-I-0086. Protections for apush thesis, human subjects are in accordance with NIAID Division of Intramural Research policies.
Phlebotomy may cause some discomfort, and a process occasionally some bleeding or bruising at the site. On rare occasions, people faint while having blood drawn. Blood drawing will not exceed 150 milliliters (30 teaspoonfuls) on any day or visit. Paper? In the course of a process essay any time frame during this study, the total amount of blood will not exceed 10.5mL/kg, or 550 milliliters over any 8-week period, which is within the safety guidelines for blood drawing practiced at the Clinical Center. Like standard phlebotomy, leukapheresis is occasionally associated with local bleeding and bruising at the site of needle insertion. Lightheadedness can also occur, and people faint on introductions rare occasions. Occasional tingling in the arms and legs can occur with the procedure and a process essay can usually be relieved by chewing a calcium-rich tablet that the staff will provide. In addition, on very rare occasions (less than 1 in every 1,000 times), malfunction of the research leukapheresis machine can result in blood loss of up to 450 milliliters. Describe A Process? Trained medical personnel who are equipped to deal with any of these potential problems will always be on argumentative essay outline model c hand during the procedure. Inclusion of Women and Minorities. Gender, Ethnicity and Race Consideration.
This study involves techniques and procedures that are currently approved for various indications. Male and describe female adult patients (18 years of essays on duty age or older) will be enrolled without preference to gender, race or ethnicity from the pool of patients that receive care in Clinics 8 at the NIH Clinical Center. Patients will be recruited from outside the NIH community by advertisements posted in the Clinical Center, the NIAID web site, and a process essay advertised in other media. Mla Reference Format? We will attempt to facilitate minority recruitment using existing NIAID community outreach efforts involving local clinics in the Washington, DC metropolitan area. In adult HIV-infected patients planning to describe a process essay interrupt HAART, patients will be fully counseled prior to entry into the study as to the potential risks of essay outline model discontinuing HAART therapy and the potential benefits of continuing HAART therapy, in the setting of describe a documented virologic and/or immunologic response. Patients who do not fully comprehend these potential risks of HAART cessation, in the opinion of the study team, will not be offered participation in the study.
Patients stopping HAART therapy will be monitored closely for virologic and mla reference paper immunologic relapse and will be offered therapy, based upon the algorithm for safety outlined above. Target enrollment for describe a process essay, this study is essay writing 300 individuals and is currently ongoing. Inclusion of Children (and Pregnant Women) Inclusion of describe Children and argumentative essay model Pregnant Women. This study will be confined to HIV-infected adults greater than or equal to 18 years of age. As an observational study there is no therapeutic benefit or clinical intervention resulting from participation in this trial, thereby children are not being denied the a process potential benefits of a research intervention. We also do not have the historical research database and in vitro findings on creative writing schools HLA linkages with LTNP in the pediatric population to make valid comparisons within that cohort. The potential risks of essay withdrawing therapy in minors have not been studied and therefore may present unknown additional risks to that study population. Comparable units specializing in pediatric HIV are available at the NIH to address this topic, should preliminary results from introductions this study warrant further evaluation in the pediatric population.
The safety of describe essay discontinuing antiretroviral therapy has not been established during pregnancy and nursing, and current guidelines continue to advise HIV-positive women to take antiretroviral therapy to prevent viral transmission to the child during that time period. Therefore, pregnant or nursing women will be excluded from this study. In The? Any woman of childbearing potential must have a negative pregnancy test within two weeks prior to study entry. All participants who engage in heterosexual intercourse must use two forms of essay reliable birth control for the duration of the top 10 writing schools study. When I entered the NIH/Oxford/Cambridge Scholars program I identified Mark Connors and Quentin Sattentau as two HIV researchers with whom I would like to train with because of their focus on HIV immunology, vaccine design, and a process essay their expertise in basic immunology techniques, flow cytometry, and microscopy. I initiated contact between the argumentative essay two individuals and they agreed to start a collaborative project with me. After studying NAbs with Mark Connors for one summer I decided I wanted to focus on antibodies that mediate ADCC. I outlined the facets of a process essay ADCC I wanted to investigate then received feedback from both mentors. I subsequently wrote the proposal that was edited by both mentors and Mark Connors made final revisions. I meet multiple times during the week with Dr. Connors to discuss my research progress and to plan future experiments.
We also conduct quarterly phone conferences with Dr. Sattentau, maintain a regular email correspondence, and meet at conferences. Apush Formula? Communication will continue in the same manner while I am in Quentin Sattentau’s lab. Selection of Sponsors and Institution. Selection of Institution.
I decided to join Columbia’s MSTP program because of its tradition of exemplary medical education, medical research, and unparalleled support offered to students from program administrators. Because of my previous research experience with HIV I knew I wanted to continue research in describe a process essay this field. Essays On Duty Military? I decided to join the NIH/Oxford/ Cambridge Scholars Program to complete my dissertation research because it would provide me access to a process a more extensive network of essay writing scientists than Columbia could. Describe A Process? Oxford has a particularly strong network of HIV investigators and the structure of its graduate program allows for a particularly specialized education. As a graduate student in the pathology department I am allowed to select seminars and essay outline model accelerated 1-day to describe a process essay 1-week courses that allow me to attain skills quickly and immediately implement them into my research. In addition, the NIH/Oxford/Cambridge Scholars program provides funding for students to take courses offered by any institution giving me access to virtually any educational opportunity necessary.
In addition, through NIH’s Foundation for Advanced Education in the Sciences I’ve had the opportunity to take courses that will help me towards my goal as in infectious disease investigator such as the top 10 creative writing Vaccine Development course I completed. The NIH/Oxford/Cambridge Scholars Program is designed so that students work with a mentor at NIH and one at a university. When I joined the program I searched for HIV investigators throughout NIH and Oxford and identified Mark Connors and Quentin Sattentau as potential mentors because I wanted to essay conduct research that had direct implications in vaccine development. Quentin Sattentau was studying how to elicit effective anti-HIV neutralizing Abs (NAbs) for vaccines and formula adjuvants to stimulate systemic and mucosal immunity. Through my search at the NIH I identified Mark Connors as a potential collaborator though he and Quentin had never collaborated before. Describe A Process Essay? I believed Dr. Research? Connors’s expertise in NAbs of long-term nonprogressors (LTNPs) would complement Dr. Sattentau’s vaccine development goals. In addition, Dr. Connors’s unique cohort of LTNPs would provide ready access to samples to study many facets of HIV infection. Essay? Finally, I believe Dr.
Sattentau’s approach to research as a PhD and Dr. Connors’ as an MD will teach me to think about science in a more practical way that is suited to me as a future MD/PhD researcher. I will follow the principles on responsible conduct of research as outlined in NOT-OD-10- 019. As an c undergraduate at UMBC I took a semester-long course entitled “Ethics/Integrity in Scientific Research” which first help me to understand the responsibility scientists have to one another and a process essay medical community honestly share information. As a Columbia medical student, I have taken the Hippocratic Oath to guide my patient care and I am expected to creative writing schools adhere to the code of ethics as outlined in student handbook. Upon joining the NIH I took an online ethics course and will continue to take refresher courses annually. At Oxford I will continue my ethics training by describe, taking the writing schools required “Ethics: Introduction to Research Ethics”. A Process Essay? Since I will have access to sensitive patient data it is essential that I maintain the confidentiality of these individuals. Military? When I started research at NIH I participated in a patient confidentiality seminar.
Oxford offers an “Ethics: Confidentiality” course in which I will enroll to describe a process better my further my understanding and ability to maintain ethical practices with regards to research. As a physician, I hope to alleviate an individual’s immediate suffering; and as a scientist I hope to contribute to long-term solutions that can prevent suffering. To work most effectively at the interface of medicine and apush formula science, I have endeavored to describe a process earn an MD/PhD. I believe that the top 10 creative writing combined degree’s greatest value lies in the perspective that it affords: to approach patient care with a researcher’s eye, and to approach research with a physician’s focus on improving the quality of life. A few years ago I conducted research on telomerase, an essay enzyme that maintains healthy chromosome length. When telomerase is upregulated, as it is in 90% of carcinomas, cells can propagate indefinitely. Introductions Essay? When telomerase levels are halved, a bone-marrow failure disease called Dyskeratosis Congenita (DC) results. While looking at yeast cells with low levels of telomerase and measuring their growth rates, I noticed two things.
The first was that cells with low levels of telomerase grew slowly. Secondly, these cells had abnormal morphologies, as do tumor cells. These observations led me to wonder whether the progression of cancer in individuals with DC was slower than in patients without it because DC patients have less active telomerase. Upon discussing this with my P.I., he acknowledged having never considered his research from that aspect. A literature search demonstrated a lack of any substantial research concerning this question. A Process Essay? Research in biochemistry affords many new advances in top 10 creative schools medicine, but through that experience the importance of keeping a broader medical picture in mind became clear to me. My goals as a physician scientist are to treat patients and conduct research that will allow me to impact patients I will never meet through therapeutic discovery; specifically serving as a creative link between science and medicine in the field of describe infectious disease. The training I will receive in Oxford’s doctorate program will prepare me to be a competitive investigator through a tailored curriculum, expert dual-mentoring, learning to work in a collaborative environment, and by giving me extensive writing experience via paper submissions and even through this grant. These are all specific skills that would be harder and take longer for me to garner through a traditional medical student experience. The advantage I have in understanding that I want to be a physician-scientist has given me the opportunity to carefully cultivate these skills early in my career.
Activities Planned Under This Award. Research 80%, Seminars/Courses 10%, Presentation/Career Development/Clinical 10% Research Skills : While working in Mark Connors’s lab I have acquired specific skills such to creatively study immunology such as learning to use flow cytometry. I discuss my research progress frequently during the week with Dr. Connors. We also have phone conferences and meet with Dr. Top 10 Writing Schools? Sattentau at numerous conferences throughout the year. Writing Skills : When I entered the program I took a grant-writing workshop sponsored by the NIH Graduate Partnership Program. I also completed a 3-day grant-writing course during my senior year of college. I will improve my writing skills through preparation of manuscripts based on my research to be submitted for publication, applying for training grants, and submission of a report for my transfer viva (qualifying exam).
I will also complete the Scientific Writing from a Reader’s Perspective seminar. Discipline specific learning : I completed the 3-day “Vaccines: Development and describe a process Evaluation of Efficacy” course offered by FAES in February 2010. I also attended “Psychiatry and HIV,” a 2-day workshop offered by the American Psychiatric Association so I could learn to effectively interact with HIV+ patients I encounter. I attend weekly seminar series hosted at the NIH such as the Wednesday Afternoon Lecture Series, Immunology Interest Group seminar series, and weekly lab meetings. Bench to bedside clinical training : I will attend the Clinical Research Training Program (CRTP) weekly rounds. I will also have the top 10 writing opportunity to describe be mentored by an infectious disease clinician. Presentations : I will continue to annually attend and present at pertinent Keystone Symposia and the Annual AIDS Vaccine conference.
I have also had opportunities to present posters at the NIH/Oxford Cambridge Scholars Program Colloquium and the Oxford Pathology Graduate Student Symposium. I have given a talk to my graduate program journal club and will have more opportunities to present my research in lab meetings. Career Development : The NIH/Oxford/Cambridge Scholars programs hosts a seminar series where leaders in government/academic research, the pharmaceutical industry, and finance speak with us about their career. I also attended NIAID Fellows retreat that focused on career development. Teaching : As I prepare to leave the lab I will be responsible for training a new research fellow. Year 1 (continued) and Year 2: Quentin Sattentau Lab (Oxford) Research 75%, Seminars/Courses 10%, Presentation/Career Development/Clinical 10%, Teaching 5% Research Skills : While working in Quentin Sattentau’s lab I will learn to apply microscopic imaging to studying HIV infection. I will have weekly meetings to discuss my research progress.
We will have phone conferences and meet with Dr. Connors at creative writing, various conferences throughout the year. A Process? I have also been assigned a graduate advisor within the pathology department but not in my specific lab who will help me to objectively evaluate my research. Writing Skills : I will improve my writing skills through preparation of manuscripts based on mla reference research my research to describe a process essay be submitted for publication and writing reviews. I will complete the following 1-day courses offered at Oxford: Writing Skills – Paper and Thesis; Doctoral Thesis Writing, Discipline specific learning : I will participate in courses and mla reference research paper Skills Workshops offered by Oxford including “Advanced Light Microscopy,” “Electron Microscopy,” and “Introduction to Statistics.”
Bench to bedside clinical training : I will attend the Nuffield Department of Clinical Medicine Grand Rounds and shadow an infectious disease clinician. Career Development : See above. I will also attend the 4-day Oxford GRADschool, a personal development course. Teaching : I will seek to be an undergraduate lab instructor and essay take the Oxford course “Teaching and Learning Skills” to prepare myself. Year 3 and Year 4: Medical School (Columbia) In the summer after 11th grade I participated in the intensive 6-week Gene Search Program at the Catholic University of formula America that introduced me to molecular biology and the exciting race to describe a process essay sequence the human genome. That summer, I learned much more than how to research paper run a gel; I learned to read and comprehend primary research articles and how to design experiments.
Because of my accomplishments that summer, I was invited to describe a process participate in an extension of the Gene Search Program during my 12th grade year. This program inspired me to pursue a career in biomedical research because I began to understand how the outline c principles I was learning in school fostered scientific discovery. As a high school senior, I worked with Dr. William Winter at Howard University School of Medicine to investigate pathways that regulate 2,3-diphosphoglycerate (2,3-DPG) levels in red blood cells (RBC). 2,3-DPG lowers the describe a process essay affinity of hemoglobin for top 10 creative writing, oxygen, thereby facilitating oxygen release to tissues. Patients suffering with sickle cell anemia have high levels of a process essay 2,3- DPG. While this effect may seem advantageous to patients with sickle cell anemia, deoxygenating hemoglobin ultimately causes red blood cells to sickle by promoting hemoglobin polymerization. Previous studies indicated that adenosine might regulate 2,3-DPG levels through an interaction with the A3 receptor. To test this idea, we indirectly measured 2,3-DPG levels by using spectrophotometry to measure a by-product of the 2,3-DPG pathway.
An exciting therapeutic prospect of our research is that an antagonist of the A3 receptor may prevent the accumulation of 2,3-DPG and essays on duty military RBC sickling in patients with sickle cell anemia. I documented this work in a five-chapter thesis, in accordance with my high school’s Science and Technology Program, and presented it at my school’s science fair, where I was awarded third place in biochemistry. During college I spent four years working with Dr. Michael Summers to investigate Moloney Murine Leukemia Virus (MuLV) dimerization. Understanding dimerization is a process essay key to introductions essay developing gene and antiviral therapies. MuLV is similar to HIV in that it is a retrovirus that packages two copies of its RNA genome. Essay? Packaging of dimerized RNA is mediated by interactions between the nucleocapsid (NC) domain of the assembling Gag polyproteins and a specific domain of the RNA called the Psi-site. Previous work in the Summers lab suggested a riboswitch mechanism for military, MLV genome packaging, where, in monomeric RNA, Psi-site UCUG segments capable of binding NC are sequestered by base pairing, but upon dimerization, become exposed to bind NC.
My project was to investigate whether similar sequences in the Psi-site could also bind NC. Using isothermal titration calorimetry and nuclear magnetic resonance, we identified short RNAs (ACAG, UUUG, and UCCG) that bind NC with nanomolar affinity. Our findings suggest that: 1) binding depends on an unpaired guanosine, 2) binding is a process essay enhanced in short RNAs containing terminal phosphates, and 3) binding affinity varies by more than one order of magnitude depending on which three nucleotides lie upstream of the mla reference format research paper guanosine. The paper I co-authored (Dey, A., et. al., 2005) extends an a process established model for genome recognition, in introductions which the NC domains of assembling Gag molecules interact with multiple X(i-3)-X(i-2)-X(i-1)-G(i) elements (X is a variable nucleotide) that appear to be preferentially exposed in a process essay the dimeric RNA. I presented this research at the 2004 ABRCMS and at multiple UMBC symposiums.
I continued to investigate potential dimerization and NC-binding regions of the introductions essay writing Psi-site using native and mutant MuLV RNA segments in gel-shift assays. As expected from our riboswitch hypothesis, we observed NC binding preferentially to RNA dimers which was also confirmed by a process essay, equilibrium dialysis. Most recently our lab published the NMR structure of paper this dimer (Miyazaki, Y., et al., 2010). During the summer of describe essay 2005 I participated in the Weill Cornell/Rockefeller/Sloan Kettering Gateways to research the Laboratory Program. I worked with Dr. Describe A Process? Nikola Pavletich toward solving the crystal structure of the Saccharomyces cerevisiae Rad4-Rad23 complex bound to a DNA substrate. Rad4-Rad23 is a homolog of human XPC-HR23B, a DNA damage-repair protein. In its mutated form, XPC-HR23B causes the disease Xeroderma Pigmentosum. Patients are extremely sensitive to UV-light and develop skin cancer during childhood. Apush Formula? I identified DNA substrates to describe a process essay be used in crystallization trials by HPLC-purifying DNA, performing gel-shift assays, and setting up crystal trays.
I presented this work in a talk before the Tri-Institutional community and during posters sessions at the 2005 Leadership Alliance National Conference and at the 2005 SACNAS National Conference. In 2006 I studied telomerase assembly in the lab of Dr. Thomas Cech at the University of Colorado at Boulder. The central role telomerase plays in protecting chromosome integrity places telomerase at the heart of two common human ailments—cancer and aging. To study how and where in the cell telomerase is mla reference research assembled from its RNA and describe a process essay protein components, we used the budding yeast Saccharomyces cerevisiae as a model organism. Formula? We sought to understand whether the noncoding telomerase RNA (TLC1) goes through a cytoplasmic phase during its biogenesis. One model is that a polyadenylated precursor form of TLC1 is exported to the cytoplasm where it associates with Sm proteins. Describe? Mtr10p then plays a role in importing the TLC1-Sm complex back into the nucleus, where the telomerase holoenzyme is assembled. Using cellular fractionation and real-time RT-PCR, we attempted to localize TLC1 in its various stages.
During the summer between my first and second year of medical school I joined the two kinds amy tan research paper lab of Mark Connors where I screened patient sera for breadth and potency of neutralizing Abs against a process HIV using a TZMBL neutralization assay. We demonstrated that that progressor serum has greater breadth in potency in neutralizing HIV than Long-Term Nonprogressors (Doria- Rose, N., et al., 2009). Studying NAbs peaked my interested in other anti-viral mechanisms mediated Abs and research paper lead to my proposed project of essay investigating antibody-dependent cellular cytotoxicity. Each research experience has shown me the many nuances of a research career. I learned about: 1) the importance of basic research in developing medicines, 2) the time, organization, and ingenuity it takes to conduct research, and 3) the vital role that a physician-scientist plays in amy tan research translating basic research into medical treatment. Although I’ve experienced frustrations and disappointment in research, the thrill of observing something new, finishing a project, or publishing a paper always outweighs these challenges. Each successive experience only increased my eagerness to a process improve health care through innovative research. [Redacted from sample.] QUENTIN SATTENTAU MENTOR STATEMENT. [Redacted from sample.] [Our Web version of writing this sample application can't reproduce the layout of the actual summary statement. See below for the data fields and critiques.]
Center for Scientific Review Special Emphasis Panel. Fellowships: AIDS Predoctoral and Postdoctoral. RESUME AND SUMMARY OF DISCUSSION: In this application, the fellowship candidate proposes to investigate antibody-dependent cellular cytotoxicity (ADCC) in HIV-infected patients do determine the extent of protection that ADCC provides. The reviewers noted that the essay candidate is top 10 writing outstanding, with a strong record of research training and accomplishment. The candidate appears to be highly motivated. Her sponsors, at both institutions, are well qualified to provide the necessary training and the letters of a process essay recommendation were uniformly laudatory. Minor weaknesses of the application included the ambitious research plan to two kinds amy tan be accomplished in describe a process two years, the risk of conducting the research at two kinds paper, two sites, and a process the failure to address pitfalls and alternatives of the research project. These weaknesses, however, did not detract from the reviewers’ enthusiasm.
This training project will have a high impact in ensuring that the candidate maintains her potential to become an independent clinical researcher. DESCRIPTION (provided by applicant): Understanding the two kinds amy tan research basis of an immune response that controls infection or provides sterilizing immunity remains a major goal in the search for effective vaccines or immunotherapies for HIV. Antibodies (Abs) induced by candidate vaccines to the surface envelope glycoprotein have not neutralized a broad array of primary virus isolates. For this reason, eliciting a cytotoxic cellular response has been the describe a process primary goal in most recent vaccine trials. However, this approach has not been successful in containing viral replication in vaccinees that have become HIV-infected. Antibody-dependant cellular cytotoxicity (ADCC) has been shown to mediate sterilizing immunity against top 10 creative challenge with pathogenic simian immunodeficiency virus [Hessel 2007]. In ADCC, Fc-bearing Abs bind viral epitopes coating an infected CD4+ target T cell and an Fc receptor bearing effector, most commonly natural killer cells (NKs), bind the Ab and essay use perforin to deliver granzymes which induce apoptosis in the target. We want to study ADCC in apush formula infected patients to understand the magnitude and characteristics of the best responses achieved by a process essay, natural infection. First, we will compare ADCC mediated by the sera of mla reference research paper a cohort of patients using a granzyme B cytotoxicity assay developed in our lab.
Based on these findings, we will select the sera of patients with the most ADCC, generate monoclonal Abs (mAbs), and characterize the mAbs based on a process essay epitope specificity, affinity, potency, breadth, IgG isotype, and Fc type. Creative Schools? We will also evaluate whether ADCC is disparate from classical neutralization. Finally, we will use microscopy to examine the essay synapse between effectors, Abs, and amy tan targets. The outcome of a process this research will provide insight into the characteristics of Abs that mediate ADCC that are likely important goals in the design of HIV vaccines or immunotherapies. Writing? Hypothesis: Antibody-dependent cellular cytotoxicity (ADCC) is a function that has been shown to mediate protection from lentiviral infection. A Process Essay? We hypothesize that variations in ADCC activity of sera are dictated by the amount, specificity, and mla reference format subclass of HIV-specific antibodies.
Aim 1: Characterize the describe a process potency of sera of HIV-infected individuals in ADCC. Aim 2: Characterize the research paper specificity and a process breadth of antibodies with ADCC activity. Aim 3: Characterize the structure and function of the essays on duty target-effector synapse using both fixed and live cell laser scanning confocal microscopy (LSCM), transmission electron microscopy (TEM) and describe a process essay cryo-electron microscopy (cryo-EM) and tomography. Understanding the role of format research paper antibody-dependent cellular cytotoxicity (ADCC) in describe a process HIV could provide important insights for induction of this activity through vaccination. This project seeks to characterize the Abs that mediate ADCC and image the functional synapse formed by cellular components involved in ADCC with the goal of thesis defining new goals for the development of essay HIV vaccines and therapeutics. Fellowship Applicant: 1.
Sponsors, Collaborators, and creative Consultants: 1. Research Training Plan: 2. Training Potential: 1. Institutional Environment Commitment to Training: 2. Overall Impact/Merit : This proposal is from an applicant who is currently enrolled in the NIH M.D./Ph.D. Describe A Process? Partnership Training Program and is a participant in the NIH/Oxford/Cambridge Scholars Program, which promotes joint research in on duty military an NIH laboratory and in a university research lab. Ultimately, she will receive her Ph.D. from describe Oxford University and complete her medical training at Columbia University. The applicant is highly recommended by introductions essay, previous research mentors and describe a process essay has an outstanding academic record. Her research experience, which includes four years of undergraduate research, is matched by her productivity; she is a contributing author on two published papers and has presented her work at numerous scientific venues.
The research plan, which derives directly from the expertise and interests of the top 10 creative schools mentor, focuses on relationships between antibody-dependent cellular cytotoxicity (ADCC) in HIV-1-infected patients, HIV-1-associated disease progression, and antibody subtype. Additional experiments, which will draw on the expertise of the co-sponsor, will investigate the target-effector synapse during ADCC. A Process Essay? These studies will be significant for their basic science and translational value. Writing? The training plan is unique in that training and describe research will be accomplished in two separate laboratories of the sponsor and co-sponsor. This proposal outlines an excellent training opportunity that will greatly benefit the applicant and her potential for amy tan research, establishing an independent research career. The applicant, who is currently enrolled in an M.D./Ph.D. Describe Essay? training program, is two kinds amy tan research described in three strong letters of a process recommendation as enthusiastic, articulate, knowledgeable, highly focused, and very inquisitive. Her undergraduate research mentor characterized her as “easily among the top two or three of the more than 200 current and former undergraduates” that he has mentored. The applicant has four years of undergraduate research experience, which involved work with the Moloney Murine Leukemia Virus, and argumentative essay outline research performed during a summer program at the Howard Hughes Medical Institute focused on studies of telomerase.
Technical approaches for which she was trained included cell growth assays, transformation, RT-PCR, isothermal titration calorimetry, NMR, and cryo-electron tomography. Describe Essay? Through her prior research experience, the applicant has been included as a contributing author on two published papers and research paper has presented eight posters and one oral presentation at various local, national, and international meetings. The applicant has an outstanding academic record (3.97 GPA) and numerous awards and recognitions reflecting superior academic performance. The collaborative project outlined in the proposal was an outgrowth of describe a process a dialog initiated by the applicant between the sponsor and co-sponsor. The applicant has provided thoughtful goals for developing a career as both a scientist and physician. 2. Sponsors, Collaborators, and Consultants:
The applicant’s mentor and sponsor, who is currently Chief of the HIV-Specific Immunity Section in the Laboratory of Immunoregulation, NIAID/NIH, is an established and productive senior investigator with research support provided by top 10 schools, the NIH. Describe A Process Essay? The co-sponsor is also a productive researcher with a consistent record of support for studies related to HIV/AIDS. The research interests and expertise of the sponsor and co-sponsor will provide excellent support for the applicant’s research and training. The expertise of the co-sponsor will be particularly relevant to paper studies outlined in Aim 3. The sponsor has trained an a process essay average of amy tan research four students per year over 20 years, suggesting an excellent training environment for the applicant. Similarly, the co-sponsor has trained nine Ph.D. trainees since 2003. During her predoctoral fellowship, the applicant will be interacting with four post-baccalaureate students and one M.D. in the sponsor’s lab, and four Ph.D. trainees in the co-sponsor’s laboratory. The latter trainees will overlap with the applicant for one year or more.
These interactions will enrich the applicant’s training. The research plan is built on a process essay studies of format research antibody-dependent cellular cytotoxicity in HIV-1-infected individuals. Describe A Process Essay? Experiments will examine the potency of sera of HIV-1-infected individuals in ADCC (Aim 1), the specificity and breadth of antibodies with ADCC activity (Aim 2), and essays on duty military the structure/function of the a process essay target-effector synapse that mediates ADCC. The central feature of the proposed research is a novel and quantitative ADCC assay (developed in the sponsor’s lab) that offers significant improvements over essays on duty in the other ADCC assays. Results generated from experiments in Aims 1 and 2 will have both basic science and translational value, while results from Aim 3 experiments will provide basic information about the mechanisms of ADCC. The applicant and sponsors are well positioned to perform these studies, since the patient populations and study procedures are already in place. The applicant is participating in the NIH/Oxford/Cambridge Scholars Program, which promotes research with a mentor at the NIH and a process essay another mentor at argumentative essay model, a university. Consistent with the Scholars Program, the describe a process research training plan includes studies and training in year 1 in the sponsor’s lab at the NIH, continued studies and training in research year 2 in the co-sponsor’s lab at Oxford, and years 3 and 4 in medical school. Training in each laboratory will include the development of specific laboratory skills, writing skill development, discipline-specific education, bench-to-bedside clinical training, career development, and opportunities for presentation of results and teaching. Training at the NIH (sponsor) will be a continuation of the current laboratory work, with increased emphasis on independent research and critical thinking. Training at Oxford (co-sponsor) will include skills development in experiments involving infectious HIV-1, microscopic imaging, and biochemical and serological techniques (such as ELISA, gel electrophoresis, and mass spectrometry).
Although the targeted patient enrollment is describe a process essay given as 300 HIV-1-infected individuals, the experimental plan does not provide details regarding the scope of studies in military Aim 1. Correlates of ADCC to be studied in Aim 1 (“rates of progression and viral loads”) were not described in describe a process sufficient detail. How will rates of progression be measured? Will viral load be documented on top 10 creative schools a continuous scale or will patient viral loads be stratified? An explanation of how the results of Aim 1 experiments will be used to guide the selection of pooled patient sera in Aim 2 would have been informative. A research project spanning the laboratories of two different principal investigators will offer diversity in training and acquired expertise, and enhance the capability of the applicant to develop an independent and describe essay productive research career. 5. Argumentative Essay? Institutional Environment Commitment to Training: The resources and facilities at a process essay, both institutions will provide outstanding environments for training and research. A more detailed plan regarding the coordination of essay writing training plans between the describe sponsor and co-sponsor would be valuable, considering the creative distance and essay time difference between the two performance sites. Training in the Responsible Conduct of Research:
Comments on mla reference format research Format (Required): The description of RCR training is brief and does not provide a detailed plan for essay, formal training. However, enrollment in two formal courses at Oxford (both focused on ethics) is writing schools mentioned. Comments on Subject Matter (Required): Training courses and certifications at the NIH and Oxford should provide information on describe essay relevant subjects. Comments on Faculty Participation (Required):
Faculty participation could not be evaluated from the description of on duty in the military RCR training. Comments on Duration (Required): The duration appears to be adequate, although exact contact hours were not provided. Comments on Frequency (Required): The frequency of training could not be discerned from the description of RCR training. Fellowship Applicant: 2.
Sponsors, Collaborators, and Consultants: 1. Research Training Plan: 2. Training Potential: 2. Institutional Environment Commitment to Training: 1. Overall Impact/Merit : This is an outstanding proposal from a highly qualified applicant. The applicant has an exemplary scholastic record, strong research history and outstanding letters of reference although she lacks a first author publication. The applicant has chosen two superb sponsors with complementary skill sets. In fact, the applicant brought these two investigators together herself. Both sponsors have excellent training track records and describe a process essay both are actively involved in the HIV arena. The primary goal of apush thesis formula this project is to characterize antibodies that mediate antibody-dependant cellular cytotoxicity (ADCC). The Connors lab at the NIH has developed a novel flow cytometric-based assay to measure granzyme B delivered to an HIV infected cells.
Using this novel assay the applicant plans to compare ADCC in HIV+ subjects with various rates of disease progression and to define the specificity and breadth of antibodies with ADCC activity (Aim 1 and 2). The third Aim to characterize the describe a process essay structure and function of the target-effector synapse will be carried out at Oxford under the essays guidance of Dr. Sattentau. This aim will use fixed and live cell laser scanning confocal microscopy and TEM to examine the samples between NK and other cells with ADCC activity. If the applicant is describe a process successful the data from this project will be highly important for HIV vaccine development. The research project however is quite ambitious and no timeline is top 10 creative given. It appears that the applicant plan to spend 1 more year in a process the Dr. Connors lab and 1 year in Dr.
Sattentau lab making it a very busy two years if the applicant plans to finish all the work they outlined. Despite the highly ambitious nature of the proposed research project the overall project goals warrant further study and the applicant herself is of the highest caliber making this application worthy of funding. The applicant has a very strong research background dating back to high school where she participated in the Gene Search Project at Howard University Hospital. As an undergraduate at UMBC she was a member of the Meyerhoff Scholars Program funded by the HHMI. The applicant has coauthored 2 papers and is the essay writing first author on 8 posters and 1 oral presentation. Essay? The applicant has extremely strong letters of introductions essay writing recommendations, one of which is from a Nobel Prize winner.
Exemplary scholastic record and many community-based volunteer positions. 2. Sponsors, Collaborators, and Consultants: Two suburb sponsors are listed. Dr. Connors, Chief, HIV-specific Immunity Section NIAID, has a long track record of high quality research and publications and a solid list of successful trainees (4/year for 20 years). The other sponsor, Dr.
Sattentau, a Professor of Immunology and Pathology at the University of Oxford, is equally meritorious with over 151 published manuscripts and solid funding record. Dr. A Process? Sattentau, also has a established track record of training PhD student (n=9) and post-docs Both sponsors have well established complementary HIV research programs that will support the two kinds paper applicants proposed research project. The planned research, if successful, could provide important information about of the a process role of ADCC in HIV infection. The project is well outlined and there are sufficient preliminary data to support the feasibility of the project. The plan is to research paper utilize a novel recently developed (Connors lab) quantitative flow cytometric assay to measure GrB cytotoxicity and determine which Abs are capable of mediating the highest level of ADCC. Describe Essay? Using this technique the applicant plans to characterize the potency of sera from subjects with different rates of amy tan research paper disease progression, characterize the specificity and breadth of antibodies with ADCC activity. Using advance microcopy techniques (fixed and live cell laser scanning confocal microcopy and electron microscopy) the applicant plans to examine the structure and function of the describe a process essay target-effector synapse.
This work will be done under the guidance of introductions Dr. Sattentau who is an expert in studying the virologic synapses. This is a highly ambitious grant. It may be difficult for the applicant to finish all the proposed work especially the a process essay work proposed in Aim 3. The applicant is calling for 300 subjects but no power calculation is shown to support that many subjects. A timeline for the proposed work would be helpful. The applicant does not anticipate any issues nor are any alternative approaches outlined.
This maybe a little naive. The research training plan is well laid out by year. The plan includes research, writing skill (grant writing course), presentation, career development, teaching (both in class room training of new personnel) and discipline specific learning (i.e. in house courses and top 10 creative writing schools seminar series, lab meetings). Letters describing each institution’s role in training the applicant were provided. Applicant states that she will interact on daily basis with section head and other senior laboratory member on a daily basis. Students also make formal presentations and attend weekly LIR, meeting, NIAID grand rounds, clinical center Grand Rounds and HIV journal club.
The training plan indicates that the applicant will be at describe a process essay, the NIH for one year and Oxford for one year and then back to medical school for the last 2 years. This raises some concerns regarding the duration of the funding (3 vs. Mla Reference Format Paper? 2 years). 5. Institutional Environment Commitment to Training: The work will be conducted at the NIH/NIAID and University of Oxford. A Process? Both institutions are of the highest caliber with access to amy tan research all the required resources.
Oxford has a program in place for graduate students to take accelerated courses and the NIH Foundation for essay, Advanced Education in essays on duty military the Sciences also has specialized courses that will facility the applicants goal to describe become an infectious disease investigator. Training in the Responsible Conduct of Research: Comments on Format (Required): On line ethics course at military, the NIH and formal classroom course at Oxford. Comments on Subject Matter (Required): Applicant states they will follow principle of research outline in essay NOT-OD-1-019. The applicant has taken semester long course on Ethics/Integrity in Scientific research. The applicant took another Ethic course upon entering the amy tan research NIH.
Oxford offers a similar course. Comments on describe a process Faculty Participation (Required): No comment on faculty participation. Comments on Duration (Required): Comments on Frequency (Required): Online course and annual refresher at the NIH. Additional Comments to Applicant (Optional): Fellowship Applicant: 1. Sponsors, Collaborators, and Consultants: 1. Research Training Plan: 2. Training Potential: 1.
Institutional Environment Commitment to Training: 1. Overall Impact/Merit : This proposal comes from an excellent candidate who is essay writing part of the essay NIH/Oxford/Cambridge Scholars program, carrying out apush thesis formula her PhD research under the guidance of describe essay two excellent researchers and mentors, Drs. Connors (NIH) and Satentau (Oxford) and argumentative essay model c will complete her MD studies at a process essay, Columbia. The primary hypothesis of this proposal is that ADCC activity levels in sera are dictated by the amount, specificity, and subclass of HIV-specific Abs. This represents a highly relevant area of research that will be tackled through 3 straightforward and well-planned aims – (i) characterize the potency of sera from individuals at essays in the military, different stages of HIV infection in ADCC (comparing to clinical status and Ab neutralization), (ii) characterize the specificity and breadth of Abs mediating ADCC (comparing the sera to panels of known neutralizing Abs), and (iii) characterize the ADCC synapse. This will involve state-of-art approaches established in the sponsors’ labs, allowing the applicant an excellent chance to perform this research.
It is a clear and well-written proposal detailing a strategy to carry out relevant research in an excellent training environment. THE FOLLOWING RESUME SECTIONS WERE PREPARED BY THE SCIENTIFIC REVIEW OFFICER TO SUMMARIZE THE OUTCOME OF DISCUSSIONS OF THE REVIEW COMMITTEE ON THE FOLLOWING ISSUES: PROTECTION OF HUMAN SUBJECTS (Resume): ACCEPTABLE. INCLUSION OF WOMEN PLAN (Resume): ACCEPTABLE. INCLUSION OF MINORITIES PLAN (Resume): ACCEPTABLE. INCLUSION OF CHILDREN PLAN (Resume): ACCEPTABLE.
COMMITTEE BUDGET RECOMMENDATIONS: The budget was recommended as requested.
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POLITICO 44: A Living Diary of the Obama Presidency. After nearly five years, we’ve decided to close down the 44 blog and will feature all White House coverage directly on the POLITICO homepage. Thank you for a process your readership, and we look forward to seeing you in 2014. Valerie Jarrett: Obama to buy health insurance by end of the day. President Barack Obama plans to sign up for health insurance through an Affordable Care Act exchange before the end of the day Monday, senior adviser Valerie Jarrett said.
Monday is the last day to sign up for paper coverage that begins on Jan. 1, though the state and federal exchanges remain open through March. The White House has not yet said whether Obama will buy insurance as a resident of the describe, District of Columbia, which has its own exchange, or as a resident of Illinois, which is part of the federal exchange. Obama speaks out against amy tan research more Iran sanctions. President Barack Obama urged Congress Friday not to enact new sanctions on describe a process Iran in the near future and he suggested lawmakers advancing such measures are making political hay of the issue. I've said to members of Congress: Democrats and Republicans. there is no need for new sanctions legislationnot yet, Obama declared during a year-end press conference at the White House. The president said he wasn't shocked that some on top 10 writing schools Capitol Hill were advancing new sanctions legislation aimed at Iran's nuclear program. In what appeared to be a thinly-veiled reference to the pro-Israel lobby, he attributed those moves to a desire to please anti-Iran political forces in U.S. I'm not surprised that there's been some talk from describe essay, some members of essays in the military, Congress about sanctions.
I think the politics of trying to describe, look tough on Iran are often good when you're running for officeor if you're in office, Obama said. The president urged lawmakers to give a six-month deal with Iran over its nuclear program time to work and to in the military, allow more in-depth negotiations on describe a process a permanent pact. If Iran suddenly tries to accelerate its nuclear capabilities, it's not going to be hard for essay outline model us to turn the dials back or strengthen sanctions even further, Obama said. I'll work with members of Congress to essay, put even more pressure on Iran, but there's no reason to do it right now, he said. We've lost nothing during this negotiation period, precisely, because there are verification provisions in place. We'll know if they're violating the terms of the agreement, Obama said. Two Kinds Paper. Let's test them. Describe. Now's the time to essay writing, see if we can get this thing done. Obama's comments came a day after White House press secretary Jay Carney warned for the first time that Obama would veto any new sanctions legislation Congress enacts before the interim deal with Iran expires. The president did not personally reiterate the veto threat Friday. However, Obama did suggest that shunting aside the describe a process essay, current prospect for a diplomatic resolution would increase the introductions, chances of a military conflict over the issue.
And he warned lawmakers that the describe, war-weary American public is in no mood for format that. It is my goal to prevent Iran from obtaining a nuclear weapon. But I sure would rather do it diplomatically. A Process. I'm keeping all options on the table, but if I can do it diplomatically, that's how we should do it, and I would think that would be the preference of everybody up on Capitol Hill, because that sure is the preference of the American people, the president said. Obama to hold news conference at 2 p.m. EST. President Barack Obama will close out the mla reference format research paper, year with a news conference at the White House on Friday. He is set to describe, take questions at 2 p.m. ET in the Brady Press Briefing Room, the White House said in updated guidance. It's a chance for the president to reflect on the year, to look ahead and to respond to pressing issues including changes to the health care mandate and two kinds amy tan reform of the National Security Agency.
Later Friday, he and a process essay the first family will leave Washington for thesis formula a two-week vacation in a process essay Hawaii. Obama commuted sentence of Deval Patrick kin. One of the eight federal prisoners granted sentence commutations by President Barack Obama Thursday is a first cousin of mla reference, Gov. Deval Patrick (D-Mass), one of the president's most devoted supporters on the national political scene. Reynolds Allen Wintersmith Jr. was sentenced to life in prison after being convicted in Illinois federal court in 1994 of conspiracy to possess with intent to distribute and distribute cocaine and cocaine base and possession with intent to distribute crack. He was 19 at the time of his arrest and 17 at the time he got involved running drugs for the Gangster Disciples gang. He is describe, 39 today and has spent the past 19 years in prison. A spokeswoman for essay writing Patrick confirmed that the 57-year-old Massachusetts governor and Wintersmith are cousins but denied any invovement in essay the drive to mla reference format paper, get the federal prisoner a rare commutation one of only describe a process, nine Obama has granted as president.
The Governor has no recollection of meeting Mr. Wintersmith (they are quite far apart in age), and believes that if they did meet, it would have been when Mr. Argumentative Essay Outline. Wintersmith was a small boy. A Process Essay. The Governor was not involved in research any application for describe a process a commutation of argumentative essay model, Mr. Describe Essay. Wintersmith’s sentence, and two kinds research paper only learned of the commutation through today’s media reports, said the essay, Patrick aide, who asked not to be named.
Wintersmith is a first cousin on Patrick's mother's side, the apush, spokeswoman added. Patrick's 2011 book, A Reason to Believe: Lessons from an Improbable Life, discusses his upbringing on the South Side of a process essay, Chicago, an uncle's addiction to heroin and the involvement of others in the neighborhood with drugs and gangs. A White House spokesman, who also asked not to be named, said Wintersmith's tie to Patrick had no impact on the commutation decision and officials do not believe Patrick ever had any contact with the feds over the matter. Wintersmith's case went to the Supreme Court in 1996, on a challenge to how his sentence and those of his co-defendants were arrived at based on essays on duty in the military distribution of both powdered and crack cocaine. The justices upheld the sentences without any noted dissent two years later in an opinion written by Justice Stephen Breyer. The lawyer who led the a process essay, drive for in the military Wintersmith's pardon, MiAngel Cody of the federal public defender's office in Chicago, declined to comment when asked about her client's family tie to Patrick. However, she said she was confident Obama would act when he learned about Wintersmith's story. We always felt like President Obama would correct this injustice with a clemency pen, Cody said in essay an interview Thursday. We just needed to give him the best clemency brief we could that would finally tell Reynolds's story . We always felt like Obama will do this and we hope it is apush thesis formula, a sign of describe a process essay, what is to come. Wintersmith's story drew attention from national groups like Families Against Mandatory Minimums because he was a very youthful offender who got a life sentence and was not convicted of a violent crime. His crime began and ended when he was a teenager, said Cody.
It was his first offense. Top 10 Creative Writing Schools. He had no priors, but under the describe, then-mandatory federal sentencing guidelines the judge had no discretion. In The Military. He could only impose a life sentence. The defense attorney said changes in sentencing guidelines and a process essay the reduction in the so-called crack-powder disparity didn't help Wintersmith. The real problem is this 18-to-1 disparity in crack versus powder sentences, which currently has rendered him and others ineligible for relief, Cody said., estimating that hundreds of inmates are in essay a similar predicament to her client. Even the reduced disparity is still a disparity that, for some serving lengthy sentences, makes them ineligible for judicial relief, she said. This certainly illustrates what we hope is a crack in the dam. Under the commutation granted Thursday, Wintersmith is essay, set to be released on apush thesis formula April 17. W.H.: Obama would veto Iran sanctions bill.
President Barack Obama would veto an Iran sanctions bill with Democratic co-sponsors, White House press secretary Jay Carney said Thursday. “We don’t think this action is necessary, we don’t think it will be enacted. If it were enacted, the president would veto it,” Carney said of the Iran sanctions bill sponsored by, among others, Democratic Sens. Describe Essay. Chuck Schumer and Robert Menendez. Carney said the Senate bill would greatly increase the chances that the United States would have to take military action against argumentative outline model Iran. He said it would also be bad for attempts at a process essay, negotiating with Iran and defy the will of the nation and the Congress. “Doing so would derail negotiations just when diplomacy is making progress,” Carney said. “It would potentially divide the international community and obviously would suggest bad faith on the part of the United States.” He added: “I think that there is introductions essay writing, overwhelming support in the country and in the Congress for a diplomatic solution to this conflict.” Update : An aide to one of the co-sponsors of the bill responds that the White House is presenting a false choice. The supporters of the bill believe it makes war less likely sanctions brought us this far, and describe essay the threat of additional sanctions can help us force Iran to get rid of their nuclear weapons in the negotiations, the aide said.
W.H.: Sochi Olympic delegation not intended to amy tan, be snub. President Barack Obama wasn’t trying to send a message about Russia’s anti-gay laws when he named an Olympic delegation with two lesbians and, for the first time since 1988, no president, vice president or first lady. “That’s not a message we would wait to send through this manner,” Carney said Wednesday. The delegation was largely viewed as a snub of Russia and essay its President Vladimir Putin, with whom Obama has been at odds on a range of issues. Carney said a half-dozen times that the delegation, headed by two kinds research, former Homeland Security Secretary Janet Napolitano and describe including tennis star Billie Jean King, former figure skater Brian Boitano and ice hockey medalist Caitlin Cahow, “represents the two kinds amy tan research paper, diversity of the United States.” “We have made no bones about the fact that we oppose and are offended by the anti-LGBT legislation in Russia,” Carney said. “We have not pulled any punches.” White House to release NSA task force report Wednesday.
The White House will on describe a process essay Wednesday release the full electronic surveillance report from President Barack Obama’s task force, press secretary Jay Carney said. The White House had said it would release the report, which carries 46 recommendations for Obama in response to revelations by thesis formula, former National Security Agency contractor Edward Snowden in January, after Obama decided which recommendations to follow. Obama received the report Dec. 13. “It’s a substantive, lengthy report, and it merits further assessment,” Carney said. Obama met Wednesday morning with the describe, surveillance task force, known formally as the Review Group on Intelligence and Communications Technologies. “While we had intended to release the review group’s full report in January, as I said earlier, given inaccurate and incomplete reports in the press about the report’s content, we felt it was important to allow people to see the full report to draw their own conclusions,” Carney said. “For that reason, we will be doing that this afternoon.” Obama will speak about the report in two kinds amy tan research paper January, Carney said. PHOTOS: Morning Money Breakfast with Valerie Jarrett. Jarrett: 'I'm not the describe a process essay, shadow chief of staff'
Valerie Jarrett says she has very specific responsibilities in the Obama White House and research focuses on them, rather than on an all-encompassing portfolio. I'm not the shadow chief of describe a process, staff, she said, responding to the use of the term by POLITICO's Ben White at introductions essay, a Morning Money breakfast. Essay. She mentioned her roles in outreach to argumentative c, women and describe a process girls, and to the business community and local government officials. Various accounts have detailed Jarrett's role in swaying Obama's views as she leverages her personal relationship with him, but she said that their private time isn't spent discussing work. We do compartmentalize, she said. Later on, pressed about amy tan paper what she and the president talk about as friends, she responded with a smile. Just stuff, she said, just stuff.
She elaborated a bit, saying they discuss our families and the same things that everybody else talks about. Jarrett also said she expects to stay in a process the White House through the end of the Obama presidency. I have the best job that I have ever had and introductions writing will ever have, she said. I serve at the pleasure of the describe a process, president . I'll be there as long as he'll have me. Jarrett: Obama won't fundraise for library while in office. President Barack Obama won't fundraise for his presidential library while in office, White House senior adviser Valerie Jarrett said Wednesday, as she downplayed a recent report that planning for the library is mla reference, well under way. He is not raising any money for it whatsoever, nor will he while he’s in office, Jarrett said at POLITICO's Morning Money breakfast.
A Tuesday report in The New York Times detailed early-stage meetings about the a process, library, but Jarrett said the process is introductions, not very far along. It's absolutely in describe a process essay the embryonic stages, she said. Jarrett was also dismissive of the apush formula, suggestion that she's trying to describe a process, push her way into the planning process. I have a big plate of responsibilities to handle at the White House, she said. You can't believe everything you read, even if it's in the New York Times. A Chicagoan like the president, Jarrett said that it's up to the president to decide whether his library will be there, in Hawaii, or elsewhere. Who knows where it's going to be, she said. As she closed out her response, she again hit the Times story, saying: The New York Times piece was not very accurate. Valerie Jarrett: No W.H. and tech 'disconnect' There's no disconnect between the White House and the tech community, Obama adviser Valerie Jarrett said Wednesday, responding to complaints from some companies that the president was too focused on HealthCare.gov in a recent meeting,
Ninety-nine percent of President Obama's time in the room for Tuesday's meeting with tech executives including Apple CEO Tim Cook and Yahoo CEO Marissa Mayer was spent discussing the companies' concerns about the National Security Agency's surveillance programs, Jarrett said at amy tan research paper, POLITICO's Morning Money breakfast. There was a presentation on the health care site for the executives by Jeff Zients, but that was before Obama joined the meeting, Jarrett said. Describe A Process. Sources at companies that attended the meeting have told various news outlets that they felt like there was too much discussion of health care and that it seemed as though the top 10 creative, White House didn't realize their primary concern was the NSA. But, Jarrett said, there was no confusion. A Process Essay. I don't think there was a disconnect at all, she said.
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Albert Einstein Reads #8216;The Common Language of Science#8217; (1941) Here's an extraordinary recording of essay Albert Einstein from the fall of 1941, reading a full-length essay in English: The essay is called The Common Language of writing Science. It was recorded in September of 1941 as a radio address to the British Association for the Advancement of Science. The recording was apparently made in America, as Einstein never returned to Europe after emigrating from describe, Germany in 1933. Einstein begins by sketching a brief outline of the development of language, before exploring the connection between language and creative schools, thinking. Is there no thinking without the use of language, asks Einstein, namely in concepts and concept-combinations for which words need not necessarily come to mind? Has not every one of us struggled for words although the connection between 'things' was already clear? Despite this evident separation between language and thinking, Einstein quickly points out that it would be a gross mistake to conclude that the two are entirely independent. In fact, he says, the mental development of the individual and his way of forming concepts depend to a high degree upon language. Thus a shared language implies a shared mentality.
For this reason Einstein sees the language of science, with its mathematical signs, as having a truly global role in influencing the way people think: The supernational character of scientific concepts and scientific language is describe a process due to the fact that they have been set up by the best brains of all countries and two kinds amy tan paper, all times. In solitude, and yet in cooperative effort as regards the final effect, they created the spiritual tools for the technical revolutions which have transformed the life of describe a process mankind in the last centuries. Their system of essays on duty concepts has served as a guide in the bewildering chaos of perceptions so that we learned to essay, grasp general truths from particular observations. Einstein concludes with a cautionary reminder that the scientific method is only a means toward an end, and that the welfare of humanity depends ultimately on shared goals. Perfection of means and confusion of goals seem--in my opinion--to characterize our age. If we desire sincerely and passionately for the safety, the welfare, and two kinds amy tan research, the free development of the talents of all men, we shall not be in want of the means to approach such a state. Even if only a small part of mankind strives for such goals, their superiority will prove itself in describe a process the long run. The immediate context of Einstein's message was, of course, World War II. Mla Reference Format Research Paper? The air force of Einstein's native country had only recently called off its bombing campaign against England. A year before, London weathered 57 straight nights of bombing by the Luftwaffe.
Einstein had always felt a deep sense of gratitude to the British scientific community for its efforts during World War I to a process essay, test the essay outline c General Theory of Relativity, despite the fact that its author was from an enemy nation. The Common Language of Science was first published a year after the radio address, in Advancement of Science 2, no. 5. It is currently available in the Einstein anthologies Out of a process My Later Years and apush formula, Ideas and Opinions . A Process? Follow Open Culture on Facebook and Twitter and share intelligent media with your friends. Or better yet, sign up for essays on duty, our daily email and a process essay, get a daily dose of Open Culture in your inbox. If you'd like to support Open Culture and our mission, please consider making a donation to our site. It's hard to rely 100% on ads, and your contributions will help us provide the best free cultural and educational materials. Mla Reference Research Paper? Find Courses on Einstein in the Physics Section of our Free Online Courses Collection. This is awesome!!
Einstein has always been a step above his competiton and a privator of peace. This is amazing, I am glad to something of this caliber posted here. Very nice to a process, hear this recording, Thank you. Tetryonics is a newly developed. Creative Writing? quantum theory of describe a process essay mass-ENERGY-Matter, stemming from a radical reinterpretation of what square numbers are in physics and its application to quantized angular momentum(QAM). Essay Outline? It can now be shown through the geometry that the QAM of planks constant is in fact the result of its quantized equilateral triangular geometry (not a vector rotation. The equilateral geometry itself gives rise to the physical properties of charge, electrical permittivity, magnetic permeability and the. rigid physical relationships between inertial mass-energy and moment in physical systems at describe essay the quantum level.
Charge(QAM/C2), in apush addition to its role as the geometric source of describe essay physical properties, also provides the. Introductions Essay Writing? quantum frame work for radiant 2D mass- energies to become 3D standing waves Matter geometries facilitating the development of describe a process large scale physical systems of atoms,compounds, stars and top 10 creative writing schools, galaxies throughout our universe. Hitherto unexplained and mysterious properties of quantum mechanics are. now revealed as having their origin in describe essay the geometry of planks constant itself. What a wonderful experience tio hear thr great man#8217;s voice. Not only extremely intelligent, but wise. Apush Thesis? Wow, this is describe essay amazing#8230;his voice reminds me a bit of Mr. Two Kinds Amy Tan Research? Clouseau, though, the essay last person you#8217;d expect to compare with Einstein lol. I really like his way of speaking (I mean the pronunciation) :) Wooow this is so great! I always wanted to know what he sounded like. He sound really really German :) Its really very glad to introductions, have a chance to listen to the voice of such great person#8230; Every science person should worship towards his great achievements and contributions in Physics#8230; With great respect E = MC^2.
His voice is like David Robert Jones#8217; from Fringe. A Process? How much I would give to just discuss his theories with him. He changed this Planet. intelligence woz paramount in This guys Life,I really admire Him; Einstein My Hero. Mla Reference Format? This is amazing. Hearing Dr. Einstein#8217;s voice is amazing. Listening to the content of his words, even more so. This completely made my day. Thank you so much for posting this! great man of everytime. OMG, can#8217;t believe when I listen, it is the voice of Markus Persson (notch) i don`t know what it is, but when i listen to it, i feel very calm. Very nice, thank you I love him very much and you gave me a wonderful gift too.
Awesome. can anybody tell me how to download this audio. African Head Charge sampled the describe essay in part for their dub classic “Language and Mentality”. Check youtube here: http://youtu.be/AfK236M7lfc. Two Kinds Amy Tan Research? m so happy that i heard voice of a great scientist. Love his accent! Does anyone know how to download this audio file? albert explanation of his theory about the discovery of the describe universe big bang change the state of the man kind mind and essay outline, help us to beleive in the power freedom of essay god hmself.he become the genius guru according to me of all time.god send him on on duty military, earth for tfis reason and will be never forget and of course his recognition until the end of describe essay time.god bless him. This won#8217;t play on a Mac. Not true, plays just fine. Profundity and intellect are concepts we have forgotten in our time of #8216;moral#8217; relativism. His voice seems to stir the emotions with interest, and introductions, yet seems to still the describe a process essay mind and soul, for all he went through as well during WWII#8230; It is redundant perhaps to mla reference research, say that his ideas have changed us as well as the #8216;modern#8217; world; And he believed in God#8230; What do people believe in today? “It seems to me that the idea of a personal God is an anthropological concept which I cannot take seriously. I feel also not able to a process, imagine some will or goal outside the human sphere.
My views are near those of Spinoza: admiration for the beauty of and belief in the logical simplicity of the order which we can grasp humbly and only imperfectly. I believe that we have to content ourselves with our imperfect knowledge and understanding and treat values and moral obligations as a purely human problemu2014the most important of all human problems.” how man can do such unexpected relation between space time and universe. goOd OMG, can#8217;t believe#8230;. Albert woOw. Writing? OMG #8230; actually always wonder how his sound will be .. amazing. u0641u0646u0627u0646 u064a u0627u0644u0628u0631u062a :)nhttps://www.facebook.com/PaGe3aSal. I love his accent. Can#8217;t believe I heard the voice of such greatest teacher in the history. :) accent of a genius. sounds fine. . . nothing to be amazed of -.-“ Richard, thanks for the pedantic buzz-kill jackass! An atom-Buddha speaks with grace and describe a process essay, outrageousness.
Each passing seasonal year quantum physics comes closer to the historical Buddha#8217;s wisdom of schools Emptiness.nWhat sure mind can conflate mind and all phenomena with Space.Without edge or centre.Space.Without limit.Space.Always accomodating.Naturally without obstacle. Everything IS relative.Relative to SPACE.How fabulous. Sounds like a cartoon character. I like it. Incredible. I like it. And the whole subject is very interesting. I#8217;m brasilian, I don#8217;t speak and listen english :( Gracias por publicar esta maravillosa grabacion del gran maestro y sabio Albert Einstein#8230;.me emociona escuchar su voz explicando el tema. Professor Ludwig Von Drake. Seems like Some Character is from Harry Potter :D.
When the greatest genius of the last. 400 years speaks, it behooves mankind to listen. Now with the revelations from Professor Douglas Stone#8217;s new account of the history of Quantum Mechanics, it is apparent that Einstein was not only the a process father of relativity, but also of quantum mechanics. Sadly, his conscientious ability to connect the practice of science (“the means”) with the goal of moral advancement (“ends”) has been lost on many of apush today#8217;s thinkers. Science and morality have always been co-dependent, as has science and a process essay, language. Science empowers us and, to borrow the cliche, “with great power comes great (moral) responsibility.” All hail the master. Extremely interesting, and very cool to hear Einstein#8217;s voice! Thank you very much. Cool German accent #8216;sounds like Boris from the Rocky and Bullwinkel cartoon, and Albert makes one understand and feel calm , thanks.
J. I need radio down load to get more information in the world and entertain with learning new things. i almost cryed listening to him, his voice is amazing. But Boris has a Russian accent. It would have been easier to understand the spoken words if I had read a transcript in formula parallel. Describe A Process Essay? It was quite an c experience to hear the voice of the man who became an describe a process essay icon of “brilliant mind”. Thesis? Interesting and exciting to hear this Man . I look like his style just a little. the mental development of the describe a process individual and his way of forming concepts depend to a high degree upon language.” Thus a shared language implies a shared mentality.
For this reason Einstein sees the language of science, with its mathematical signs, as having a truly global role in influencing the way people think. the mental development of the individual and his way of introductions forming concepts depend to a high degree upon language.” Thus a shared language implies a shared mentality. A Process Essay? scientific method of thinking depend on the language. Scientific methods of thinking depend on the language and argumentative essay model, the high thinking level can#8217;t be expressed without the a process essay language. The cool German accent also helped fiend Hitler along his rise to power, achieve good and bad but most certainly notable Unfortunately both men turned out misguided Hitler in his ego driven land grabs, or desire for reunification of the German peoples so brutally torn asunder and treated less than human(sic) and Einsteins later admission that his model just didn#8217;t compute when the slowing effects of the aether was taken into account and so simply ignored in his desire to mla reference research paper, prove his math, ego rears it#8217;s ugly head once more When asked how it felt to be the describe world#8217;s smartest man he replied you should ask Nicola Tesla. So cool accents aside, maybe that pedestal isn#8217;t as high as we think? We're hoping to rely on loyal readers, rather than erratic ads. Click the outline model c Donate button and support Open Culture. We thank you! Get the best cultural and essay, educational resources on the web curated for you in a daily email. We never spam.
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Dec 19, 2017 Describe a process essay,
essay on men Pope wrote his Essay on Man in a process essay rhyming verse. Certainly today, we think anybody that writes poetry is one who is research paper a bit odd, to say the least. Back in describe a process essay the eighteenth century, it was not so strange. Pope stated that he had two reasons for writing his essay in essays on duty such a manner. First, he thought that principles, maxims, or precepts so written, both strike the describe a process reader more strongly at first, and are more easily retained by him afterwards.
The second reason that Pope gave is that he thought that he could express himself more shortly this way than in prose itself. I here make comments about the expressions and thoughts of Pope in his essay. I have quoted at length from his essay. Certainly there is format research much I have left out, because, likely, certain verses referred to describe a process essay events, persons and things of the early eighteenth century which, quite frankly, I am unfamiliar with. Spattered throughout Pope's work are references to essays in the military God and describe essay, His great domain. Such references in the writings out of the eighteenth century are not strange.
The livelihood of writers, by and large -- as was with the case of all artists back then -- depended almost entirely on the generosity of church and state, so it was necessary in those days that writers give due regard to two kinds amy tan religious authority. Believing that if Pope were looking over my shoulder he would have no objection, I have left out religious epaulets. Within the first few lines, we see Pope wondering about the fruitlessness of describe a process essay life. We have no choice: we come to introductions essay it, look out and then die. Essay. What we see as we look out on the scene of apush formula man is a mighty maze! But Pope does not think this complex of existence is without a plan.
Man might sort through the maze because he has a marvelous mental faculty, that of reason; man can determine the essay nature of the world in which he lives; he can see that all things have bearings, ties and strong connections and on duty in the military, nice dependencies. He, who thro' vast immensity can pierce, See worlds on worlds compose one universe, Observe how system into system runs, What other planets circle other suns, Look'd thro'? or can a part contain the whole? Is the great chain that draws all to agree, - And, drawn, supports - upheld by God or thee? In his next stanza, Pope makes reference to a process essay presumptuous man!
Why should one be disturbed because he cannot immediately figure out all of the mysteries with which he is presented? It cannot be expected that one part of existence (man) should understand all the other parts, he then continues: As of thy mother Earth, why oaks are made. Taller or stronger than the weeds they shade. And all that rises, rise in due degree; Then, in the sale of reas'ning life, 'tis plain. There must be, somewhere, such a rank as Man. When the dull ox, why now he breaks the clod,
Is now a victim, and two kinds research paper, now Egypt's god, - Then say not Man's imperfect, Heav'n in fault, - Say rather Man's as perfect as he ought: His knowledge measur'd to describe a process essay his state and place, His time a moment, and a point his space. Pope continues with this theme into introductions, his third stanza, in saying Heav'n from all creatures hides the book of fate, and continues: The lamb thy riot dooms to bleed to-day, Had he thy reason, would he skip and play? Pleas'd to the last he crops the flow'ry food, And licks the hand just rais'd to shed his blood. Who sees with equal eye, as God of all, A hero perish, or a sparrow fall,
Atoms or systems into describe a process, ruin hurl'd, And now a bubble burst, and now a world. Then giving way to his religious bent, makes reference to essay outline c the great teacher Death and a process essay, continues with his most famous lines: Hope springs eternal in the human breast; Man never is, but always to introductions writing be blest: The soul uneasy and describe a process essay, confin'd from home, Rest and expatiates in a life to come. Next, Pope deals with native people of the uncivilized territories of the world, and how they do not get hung up on such large questions as are expressed in mla reference research Pope's essay: Lo, the essay poor Indian! whose untutor'd mind.
Sees God in clouds, or hears him in the wind; His soul proud Science never taught to two kinds amy tan research stray. Far as the describe a process essay solar walk or milky way; Yet simple Nature to his hope has giv'n, Behind the cloud-topp'd hill, a humbler heav'n; Some safer world in depth of woods embrac'd, Some happier island in amy tan research paper the wat'ry waste, Where slaves once more their native land behold, No fiends torment, no Christians thirst for gold! To be, contents his natural desire; He asks no angel's wing, no seraph's fire:
But things, admitted to describe a process essay that equal sky, His faithful dog shall bear him company. Next, we see Pope start to develop the theme that runs throughout his essay; man is part of a larger setting, a part of two kinds research paper nature. Man depends on nature for his very substance, and yet, treats her roughly. Destroy all creatures for thy sport or gust, Yet cry, if Man's unhappy, God's unjust; Ask for what end the heav'nly bodies shine, Earth for whose use, Pride answers, 'Tis for mine!
For me kind Nature wakes her genial pow'r, Suckles each herb and spreads out ev'ry flow'r; Pope asserts that man is ruled from within, by describe essay, his reason and by his passion. Better for us, perhaps, it might appear, Were there are harmony, all virtue here; That never air or ocean felt the wind;
That never passion discompos'd the mind. But all subsists by apush, elemental strife; And passions are the elements of life. The gen'ral Order since the essay whole began. Is kept in Nature, and is kept in top 10 schools Man.
Passion may be equated to instinct; and instinct is the sole guide of animals. Instinct is all that animals need as evolution has fitted each animal to his home environment, unlike man who is in want of the strength of bulls, the fur of bears. Here with degrees of swiftness, there of force: All in a process essay exact proportion to the state; Nothing to essays on duty add, and describe a process essay, nothing to abate. Each beast, each insect, happy in its own: Is Heav'n unkind to Man, and Man alone?
Shall he alone, whom rational we call, Be pleas'd with nothing, if not bless'd with all? Again, Pope emphasizes how nature all good and thesis formula, wise. and what it gives, and what denies has perfected itself and many of its creations: The spider's tough how exquisitely fine! Feels at each thread, and lives along the line: In the nice bee, what sense so subtly true. From pois'nous herbs extracts the healing dew?
In nature, we find life in a complete variety, - vast chain of being everything beast, bird, fish, insect. Or in the full creation leave a void, Where, one step broken, the great scale's destroy'd: From Nature's chain whatever link you strike, Tenth or ten thousandth, breaks the chain alike. The point, I think, is that there is a fearful balance of nature in all its variety, and we dare not destroy one aspect of nature for describe fear of destroying the argumentative outline model whole. All this dread order break - for whom? for thee? Vile worm! - oh madness! pride! impiety! In the last line of Pope's first epistle, he bangs home the importance of the ruling mind of nature, that while some parts might seem to us to be absurd, it is a process part of the general frame that all of nature, including ourselves, are but parts of one stupendous whole.
This whole body of nature is through all life and introductions writing, extends throughout all of the universe and a process, operates unspent. Pope concludes his first epistle: Safe in the hand of one disposing Pow'r, Or in the natal, or the mortal hour. All Nature is but Art, unknown to thee; All chance, direction, which thou canst not see. All discord, harmony not understood, All partial evil, universal good: And, spite of pride, in erring reason's spite, One truth is clear, whatever is, is thesis right.
Pope opens his second Epistle much the same as he opened his first. What is the function of man, positioned as he is essay somewhere between a god and formula, a beast. Man, during that brief interlude between birth and death, experiences a chaos of describe a process thought and passion, all confus'd. He finds on earth the Great lord of all things, yet a prey to all. Man's function, Pope concludes, is to two kinds amy tan paper make a proper study of mankind ; man is to know himself. What man will come to know is that he is ruled by passion; passion is the describe essay ruler and reason it's counsellor.
Alas what wonder! Man's superior part. Uncheck'd may rise and climb from apush formula art to art; But when his own great work is but begun, What Reason weaves, by describe a process, Passion is undone. It is in the nature of man to first serve himself; but, on account of reason, to do so with the long range in view. Two Principles in human nature reign; Self-love, to urge, and Reason, to restrain; Self-love still stronger, as its objects nigh;
Reason's at distance, and in prospect lie: A person is driven by passion, driven by paper, his desire for pleasure; temptation is strong and passion is thicker than arguments. However, a person soon learns through bitter experience that one cannot let his or her passions run wild. Attention, habit and experience gains; Each strengthens Reason, and Self-love restrains. Self-love and Reason to one end aspire, Pain their aversion, Pleasure their desire, Pleasure, or wrong or rightly understood, Our greatest evil, or our greatest good. Passions, tho' selfish, if their means be fair, List under reason, and deserve her care.
On life's vast ocean diversely we sail, Reason the card, but passion is the gale;2. Love, Hope, and describe essay, Joy, fair Pleasure's smiling train, Hate, Fear, and Grief, the family of Pain, These mix'd with art, and to due bounds confin'd,
Make and maintain the balance of the formula mind: Pope's theme is a process again repeated: the two driving forces of man are his reason and his passion. However, passion is the paper king and reason but a weak queen. What can she more than tell us we are fools? Teach us to mourn our nature, not to essay mend. A sharp accuser but a helpless friend! Reason (th' Eternal Art, educing good from ill) is not a guide but a guard.
Passion is the top 10 writing mightier pow'r. Envy, Pope points out as an aside, is something that can be possessed only by those who are learn'd or brave. Describe Essay. Ambition: can destroy or save, and makes a patriot as it makes a knave. With Pope's thoughts, it soon becomes clear one should not necessarily consider that envy and ambition are in themselves wrong. They are moving forces in a person and if properly guided, can serve a person well. As, in some well-wrought picture, light and shade. And oft so mix, the diff'rence is too nice, Where ends the format research paper virtue, or begins the vice. And virtuous and describe a process, vicious ev'ry man must be, Few in the extreme, but all in the degree;
Each person is driven by essays military, self-love, but on the same occasion each on the other to depend, a master, or a servant, or a friend, bids each on describe a process essay other for assistance call. Each person seeks his own happiness, seeks his own contentment; each is proud in what he or she has achieved, no matter what another person might think of those achievements. Whate'er the passions, knowledge, fame, or pelf, Not one will change is neighbour with himself. The learn'd is essay writing happy nature to a process explore, The fool is happy that he knows no more; The rich is happy in the plenty given, The poor contents him with the essays care of a process Heaven, See the blind beggar dance, the cripple sing. The sot a hero, lunatic a king; The starving chemist in his golden views.
Supremely bless'd, the essays on duty in the poet in his Muse. None of a process essay us should be critical of another person's choice in essay writing life, who is to know it is describe a process essay right. Two Kinds Paper. Behold the child, by a process essay, nature's kindly law, Pleased with a rattle, tickled with a straw: Some livelier plaything give his youth delight, A little louder, but as empty quite: Scarfs, garters, gold, amuse his riper stage, And beads and prayer-books are the toys of age:
Pleased with this bauble still, as that before, Till tired he sleeps, and essays military, life's poor play is o'er. Pope returns, in his third Epistle, to his ever present theme, all is natural in nature and man is describe essay a part of nature. He first observes how plastic nature is, how everything is dependant on one and the other, is attracted to one and the other, down even to single atoms. Everything it's neighbour to mla reference research paper embrace. (While Pope did not do so, he might just as easily have observed that things in nature repel one another, equally so. Describe. All things, in mla reference the final analysis, are held in the balance, suspended, so it seems, between the two great forces of describe attraction and repulsion.) All forms that perish other forms supply, (By turns we catch the vital breath, and die) Like bubbles on the sea a matter borne, They rise, they break, and to that sea return. Nothing is foreign; parts relate to apush whole: Then, Pope picks up once again his theme of the ruling principles, reason and passion.
Here in a process essay his third Epistle, he refers to instinct as the unerring guide that reason often fails us, though sometimes serves when press'd. But honest instinct comes a volunteer, Sure never to o'ershoot, but just to hit, While still to mla reference format research wide or short is describe essay human wit; Sure by quick nature happiness to thesis gain, Which heavier reason labour at in vain.
Instinct can be seen at work throughout nature, for a process example, Who make the spider parallels design . without rule or line? Not just the spider does things by instinct, man does. The obvious example is his artistic work, but our instincts serve us on a much broader range. Argumentative Outline C. Think! And you will wonder about many of the daily things that are done, automatically it seems. A Process. What, exactly, is essays on duty it that prompts us to do things. Essay. Who calls the council, states the certain day, Who forms the c phalanx, and who points the way?
Pope then comes to a rather critical passage in describe a process his essay, when he deals with family units in the animal kingdom versus human beings. The fact of the matter is, family units do not count for much in the animal kingdom, at any rate, not for on duty long. However, family connections for human beings extend over a long period, indeed, over a lifetime. I would observe that it is an evolutionary development, needed because of the long time required before a child passes into adulthood. A Process Essay. These family feelings are important for the development and essays on duty military, cohesion of the family, but not necessarily good when extended to the larger group, society as a whole (this is a theme that I have developed elsewhere (EconEcon.doc) and which someday I hope to put up on describe a process the 'net.). Writing. Thus beast and bird their common charge attend, The mothers nurse it, and the sires defend: The young dismiss'd to wander earth or air, There stops the instinct, and there ends the a process essay care; The link dissolves, each seeks a fresh embrace,
Another love succeeds, another race. A longer care man's helpless kind demands; That longer care contracts more lasting bands: Reflection, reason, still the ties improve, At one extend the interest, and the love; With choice we fix, with sympathy we burn; Each virtue in each passion takes its turn; And still new needs, new helps, new habits rise. That graft benevolence on charities. Still as one brood, and as another rose, These natural love maintain'd, habitual those:
The last, scarce ripen'd into perfect man, Saw helpless from him whom their life began: Memory and forecast just returns engage; That pointed back to youth, this on to age; While pleasure, gratitude, and essays in the, hope, combined, Still spread the interest, and preserved the kind. Pope then, continuing with his third Epistle, returns to his principle and the power of nature. Nature is a driving gale, a fact which can be observed in the voice of nature and which we can learn from the birds and describe a process, the beasts. It was the power of nature that built the ant's republic and the realm of bees. Pope observes anarchy without confusion.
Their separate cells and properties maintain. Mark what unvaried laws preserve each state;- Laws wise as nature, and as fix'd as fate. In vain thy reason finer webs shall draw; Entangle justice in her net of law; And right, too rigid, harden into wrong,
Still for the strong too weak, the weak too strong. Yet go! and thus o'er all the creatures sway; Thus let the wiser make the amy tan research rest obey; And for those arts mere instinct could afford, Be crown'd as monarchs, or as gods adored. It is the same voice of nature by which men evolved and cities were built, societies were made.
That while men in a process the gradual and slow build-up ravished one another with war, it was commerce that brought about civilization. Mla Reference Format Research. Men came to describe new countries with war-like intentions, but soon became friends when they realized there was much more profit in trade. When love was liberty, and nature law: Thus states were form'd; the name of writing king unknown, Till common interest placed the sway in one. 'Twas Virtue only, or in a process arts or arms, So, it was trade that built civilizations, and Pope observes, that it was tradition that preserves them. Convey'd unbroken faith from sire to essays in the son; The worker from the work distinct was known,
Then, continuing in this historical vein, Pope deals with the development of government and of laws. So drives self-love, through just and through unjust. To one man's power, ambition, lucre, lust: The same self-love, in all, becomes the cause. Of what restrains him, government and a process, laws: For, what one likes if others like as well, What serves one will, when many wills rebel?
How shall we keep, what, sleeping or awake, A weaker may surprise, a stronger take? His safety must his liberty restrain: All join to guard what each desires to gain. Forced into virtue thus by self-defence, Ev'n kings learn'd justice and essay outline c, benevolence: Self-love forsook the path it first pursued, And found the private in the public good. 'Twas then, the studious head or generous mind, Follower of a process essay God or friend of human-kind,
Poet or patriot, rose but to restore. The faith and moral Nature gave before; Relumed her ancient light, not kindled new; If not God's image, yet his shadow drew; Taught power's due use to top 10 people and to describe a process kings; Taught not to thesis slack nor strain its tender strings; The less or greater set so justly true, That touching one must strike the other too;
Till jarring int'rests of themselves create. Th' according music of a well-mix'd state. Such is the world's great harmony, that springs. From order, union, full consent of things: Where small and great, where weak and mighty made. To serve, not suffer, strengthen, not invade; More pow'rful each as needful to the rest, And in proportion as it blesses, blest; Draw to one point, and to one centre bring. Beast, man, or angel, servant, lord, or king.
Pope makes a side observation that while government is necessary, its form is of less importance, what is important, is a process essay a good administration: For forms of government let fools contest; Whate'er is best administer'd is best: Pope then concludes in his third Epistle, emphasizing that regard for oneself and his family has to be different than regard for the whole of society, that nature link'd the gen'ral frame and bade self-love and writing, social be the same. In his last Epistle on the Essay of Man, Pope deals with the describe essay subject of happiness. It may be any one of a number of things, it depends on the person: good, pleasure, ease, content! whatever thy name. That happiness as a plant of celestial seed will grow, and if it doesn't, one should not blame the soil, but rather the essays way one tends the soil. Though man may well seek happiness in many quarters, it will only be found in describe a process nature. Man should avoid extremes. He should not go about in argumentative essay outline model life trusting everything, but on essay the same occasion neither should he be a total skeptic. Take Nature's path, and made Opinion's leave; All states can reach it and all heads conceive;
Obvious her goods, in no extreme they dwell; There needs but thinking right, and meaning well; And mourn our various portions as we please, Equal is common sense, and common ease. To Pope, pleasure does not last, it sicken, and all glories sink. To each person comes his or her share and who would more obtain, Shall find the top 10 schools pleasure pays not half the pain. To be rich, to be wise: these are both laudable goals and a person looking about will always be able to find others who have riches and wisdom in varying degrees, but it cannot be concluded to a process any degree that they are happy. Happiness comes when one has health, peace, and competence.
It is not clear to me from Pope's lines how one might secure peace and essays on duty military, competence; health, he says, consists with temperance alone. It is in describe essay the nature of man to essays in the military attempt to change things; he is never happy with things as he finds them; never happy with his fellow man; never happy with the describe a process essay world about him. We forever strive to argumentative outline make things perfect, a state that can hardly be define in a process human terms. Those that reflect on man's condition will soon have Utopian dreams. But still this world, so fitted for the knave, Contents us not. A better shall we have?
A kingdom of the just then let it be: But first consider how those just agree. The good must merit God's peculiar care; But who but God can tell us who they are? It all too often appears to us that virtue starves, while vice is fed. Essays In The. One might wish for man to be a God and for earth to be a heaven, both God and heaven coming from the imaginations of man. But, Pope concludes: 'Whatever is, is right.' -- This world, 'tis true.
Of fame, Pope says, it is but a fancied life in others' breath . Describe Essay. All that we feel of it begins and ends in the small circle of our foes and friends . It will get you nothing but a crowd of stupid starers and writing, of loud huzzas. Of wisdom, Pope attempts a definition and points out how often the wise are bound to essay trudge alone with neither help nor understanding from his fellow man. In parts superior what advantage lies! Tell, for essays military you can, what is it to be wise? 'Tis but to know how little can be known ; To see all others' faults, and feel our own:
Condem'd in a process essay business or in mla reference format arts to drudge, Without a second, or without a judge: Truths would you teach, or save a sinking land? All fear, none aid you, and few understand. And so we arrive at describe essay the last of Pope's lines. Show'd erring Pride, WHATEVER IS, IS RIGHT; That Reason, Passion, answer one great aim; That true Self-love and Social are the same . 1 The Poetical Works of format research paper Alexander Pope which includes Dr.
Johnson's 65 page biography on a process Pope, Essay on Man (31 pp.); Essay on Criticism (17 pp.), Rape of the essay writing Lock (19 pp.), The Dunciad (31 pp.). My vintage copy has within it two frontispiece Steel Engravings (Philadelphia: Hazard, 1857). 2 Here, again, we see Pope refer to the analogy of the sailing ship on a process the sea finding its way only with compass (card) for outline direction and the wind in the sails to describe a process essay drive the vessel along.