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Smalls-Mantey, Sample F31 Application and Summary Statement. We are truly indebted to thesis the grantee who allowed us to post this outstanding F31 sample application to help the next generation of investigators write applications. The F31 sample application below doesn’t reflect the difference for college complex layouts of the brenner actual SF 424 PDF forms. Instead, we’ve provided a list of causes depression essay key fields from those forms and brenner thesis the applicant’s responses. In addition, we redacted some applicant-specific information such as contact information, publications in essay the chosen press, and budget specifics. The text of this application is copyrighted. You may use it only for nonprofit educational purposes provided the document remains unchanged and brenner the PI, the grantee organization, and NIAID are credited. Questions?
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[Our Web version of this sample application can't reproduce the layout of the actual PDF forms. Performance sites are in New York, Maryland, and essay over the United Kingdom.] Research Related Other Project Information. [Our Web version of this sample application can't reproduce the brenner thesis layout of the actual PDF forms. Difference Between Essay And Personal? Here are the key fields from that form and the applicant's responses.] Understanding the brenner basis of an immune response that controls infection or provides sterilizing immunity remains a major goal in how to an application essay descriptive the search for effective vaccines or immunotherapies for brenner, HIV. Essay The Chosen? 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 brenner thesis primary goal in most recent vaccine trials.
However, this approach has not been successful in uk containing viral replication in vaccinees that have become HIV-infected. Antibody-dependant cellular cytotoxicity (ADCC) has been shown to thesis mediate sterilizing immunity against film resume cv, challenge with pathogenic simian immunodeficiency virus [Hessel 2007]. Brenner? 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 gay marriage essay Ab and 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 brenner 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 how to write descriptive sera of brenner patients with the most ADCC, generate monoclonal Abs (mAbs), and characterize the mAbs based on epitope specificity, affinity, potency, breadth, IgG isotype, and difference between statement Fc type.
We will also evaluate whether ADCC is disparate from classical neutralization. Finally, we will use microscopy to examine the thesis synapse between effectors, Abs, and targets. Write An Application Essay Descriptive? The outcome of this research will provide insight into thesis, 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 sera are dictated by the amount, specificity, and film resume cv subclass of HIV-specific antibodies. Aim 1 : Characterize the potency of brenner thesis sera of the chosen HIV-infected individuals in ADCC. Aim 2 : Characterize the specificity and brenner breadth of antibodies with ADCC activity. Aim 3 : Characterize the structure and function of the film resume cv 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. Understanding the role of antibody-dependent cellular cytotoxicity (ADCC) in HIV could provide important insights for induction of brenner thesis this activity through vaccination.
This project seeks to characterize the Abs that mediate ADCC and image the functional synapse formed by between and personal cellular components involved in ADCC with the goal of thesis defining new goals for the development of HIV vaccines and film resume cv therapeutics. Gallo RC, Salahuddin SZ, Popovic M. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science. 1984; 224: 500-3. Barre-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, et al. Brenner? Isolation of a T-lymphotropic retrovirus from write essay descriptive, a patient at thesis risk for acquired immune deficiency syndrome (AIDS).
Science. 1983; 220(4599): 868-71. Organization WH. Global summary of the AIDS epidemic, December 2007. Difference Between Essay And Personal For College? 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. Thesis? 2007; 449(7158): 101-4. www.hivresearh.org. RV144 Phase III HIV Vaccine Trial Press Release. 2009. Chung A, Rollman E, Johansson S, Kent SJ, Stratov I. The utility of ADCC responses in HIV infection.
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. Forthal DN, Landucci G. Gay Marriage Discursive Uk? 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 thesis HIV-infected subjects. J Virol. 2008; 82(11): 5450-9. Gomez-Roman VR, Florese RH, Patterson LJ, Peng B, Venzon D, Aldrich K, et al.
A simplified method for film resume cv, 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. Loss of mismatched HLA in leukemia after stem-cell transplantation.
N Engl J Med. 2009; 361(5): 478- 88. 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 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 thesis efferent cellular interactions in natural resistance directed against MHC class I deficient tumor grafts. J Immunol. Film Resume Cv? 1988; 140(2): 671-8. De Maria A, Ferraris A, Guastella M, Pilia S, Cantoni C, Polero L, et al. Expression of brenner HLA class I-specific inhibitory natural killer cell receptors in HIV-specific cytolytic T lymphocytes: impairment of specific cytolytic functions. Difference And Personal Statement? 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 a correlation between antibody-dependent cellular cytotoxicity-mediating anti-HIV-1 antibodies and brenner thesis prognostic predictors of HIV infection. 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 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. Film Resume Cv? Failure of brenner ADCC to predict HIV-associated disease progression or outcome in a haemophiliac cohort. Clin Exp Immunol. 1990; 81(1): 5-10.
Koup RA, Sullivan JL, Levine PH, Brewster F, Mahr A, Mazzara G, et al. Between Statement? Antigenic specificity of antibody-dependent cell-mediated cytotoxicity directed against human immunodeficiency virus in antibody-positive sera. Brenner Thesis? J Virol. 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 gay marriage discursive essay, HIV. Current HIV research. 2007; 5(6): 625-41. Sattentau Q. Avoiding the void: cell-to-cell spread of human viruses.
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. 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. 2004; 199(2): 283-93. Groot F, Welsch S, Sattentau QJ.
Efficient HIV-1 transmission from brenner thesis, macrophages to T cells across transient virological synapses. Difference Between Essay For College? Blood. 2008; 111(9): 4660-3. Martin N, Welsch S, Jolly C, Briggs JA, Vaux D, Sattentau QJ. Virological synapsemediated spread of brenner thesis human immunodeficiency virus type 1 between T cells is sensitive to entry inhibition. J Virol. 2010; 84(7): 3516-27. Intellectual Support : My mentors Mark Connors and Quentin Sattentau are leading experts in how to write an application descriptive their field and have mentored numerous people that have gone on to successful careers in brenner science. 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 battle essay NIH I will have received extensive support of staff from brenner thesis, 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. I have already participated a Vaccine Development course. At Oxford I will take seminars at the Centre for Excellence in Teaching and Learning for film resume cv, training in brenner thesis teaching skills.
I will also take courses pertinent to gay marriage discursive essay uk my research offered at the Dunn School of Pathology. Both the NIH and Oxford have libraries and IT staff that can aid me in brenner 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 personal desktop computer. Difference Between Essay Statement? Bench space is shared within the lab. Safety – In order to thesis ensure our safety from hazardous blood samples we work under laminar flow hoods in a P2 facility with P3 practices. Samples – We receive blood samples from depression essay, patients enrolled within our protocol. We also have access to thesis the NIH blood blank for normal human blood samples. As provided by Quentin Sattentau: “Oxford University is held in high international regard for depression essay, its strong teaching and research background and its unique and personal teaching style.
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 brenner 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 causes depression essay each of the brenner thesis 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 gay marriage discursive essay uk term time, and a regular series of internal seminars from brenner thesis, leading and more junior University and Departmental investigators and students. Adjoa will attend and participate in difference and personal statement the weekly lab journal club, in which scientific papers are taken apart critically by members of the group, and a weekly laboratory meeting in which each lab member presents their ongoing research. Adjoa will also be encouraged to chat to brenner thesis other members of the department during tea lunch and coffee breaks, a longstanding Oxford institution! The Department has a fully equipped quiet library for literature research and the chosen other reading and thesis writing. Adjoa will have her own writing up space close to essay the chosen her work bench, equipped with a portable computer and brenner thesis if required, an external screen.
Adjoa will have full access to all core facilities, including the imaging suite with multiple light microscopes, a flow cytometry and sorting suite, an electron microscopy facility with full technical and scientific support. We also have strong connections with the biochemistry and battle gettysburg chemistry departments and the Weatherall Institute of Molecular Medicine at brenner 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 associated incubators and ancillary equipment that is gay marriage, 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 brenner thesis associated incubators and between and personal for college ancillary equipment, in which HIV-1 is grown and used to infect cells. Flow cytometry. Brenner Thesis? The department has a core flow cytometry facility with three BD analyzers (2 x FACScalibur 2 x LSR2) and film resume cv 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 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 a new CCD camera set up with a Zeiss Axiovert 200 microscope for fixed and live cell work in thesis 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 which are maintained and run as a central service facility by a skilled dedicated operator. Our collaborator in Oxford (Kay Grunewald) is located at the University Churchill campus, which is 4 miles from the Pathology Department. 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. 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 causes teenage depression essay national defense. Since middle school I have been preparing for brenner thesis, a career in causes depression essay science. At Eleanor Roosevelt High School I was enrolled in the rigorous Science and Technology Program during which time in brenner thesis participated in the Gene Search Project and teenage depression essay researched biochemical pathways that influence sickle cell anemia with Dr. William Winters at brenner thesis Howard University Hospital. This experience taught me how research and medicine are intertwined and inspired me to become a physicianscientist. At UMBC I was a member of the Meyerhoff Scholars Program and film resume cv an HHMI Undergraduate Research Scholar where numerous lab experiences, seminars, rigorous classes, and multiple opportunities for scientific presentations prepared me for brenner, a career as a scientist.
My lab skills and understanding of a research career increased exponentially during my four years in Michael Summers’ lab. Not only did I learn about protein purification, gel electrophoresis, NMR, and ITC while studying MuLV RNA packaging, but more importantly of the time and discipline necessary for excellent research and the internal drive that keeps one focused. Working with Dr. Battle Essay Gettysburg? 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 my graduate studies. The medical education I’ve received at Columbia has given me a unique perspective with which I approach scientific questions. Under the thesis tutelage of film resume cv Mark Connors and Quentin Sattentau, leaders in their fields on nonprogressive HIV infection and viral transmission, my understanding of infectious disease and my capacity to pursue further research in these fields will be greatly enhanced. In addition, the thesis courses, medical preceptorships, presentations, teaching, and career development activities I am undertaking in the forthcoming years make me an difference between for college excellent P.I. for 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 brenner Research Careers Scholar 2005 Abby Rockefeller Mauze Award Charitable Trust Scholar for 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. Film Resume Cv? 2005. Composition and sequence-dependent binding of RNA to the nucleocapsid protein of Moloney murine leukemia virus. Biochemistry.
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. Thesis? J Mol Biol.
404(5), 751-772. Smalls-Mantey A, Winter W. 2003. Film Resume Cv? Biosynthesis of 2,3-diphosphoglycerate in Erythrocytes. Poster presentation at brenner thesis ERHS Science Fair and Prince Georges County Science Fair. March 2003. Smalls-Mantey A, Dey, A, Phillip C, Summers MF.
2004. Characterization of High-Affinity Nucleocapsid Protein Binding Sites Within the write an application descriptive Moloney Murine Leukemia Virus RNA Packaging Signal. Poster presented at 2004 Annual Biomedical Research Conference for brenner thesis, Minority Students, November 2004. Smalls-Mantey A, Min J, Pavletich N. 2005. Structural and Biochemical Studies of the Yeast Rad4-Rad23 Complex Bound to DNA. Poster presented at Tri-Institutional Gateways to the Laboratory Program Symposium and 2005 Leadership Alliance.
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. How To An Application? April 2007. 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 Keystone HIV Vaccines (X5) Meeting. March 2010. Smalls-Mantey A, Klein R, Doria-Rose N, Laub L, Rood J, Migueles S, Sattenatu. Brenner Thesis? 2010. HIV-Specific Antibodies Mediate Rapid Antibody-Dependent Cellular Cytotoxicity Against Primary HIV-Infected CD4+ T Cells. An Application? Poster presented at 2010 Oxford Pathology Department Graduate Student Symposium.
June 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 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. Brenner? 2010. Uk? 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 brenner thesis very top priorities in the field of HIV-specific immunity. Our laboratory has assembled the best techniques and reagents in the field to carry out this project.
We have extensive experience in HIV-specific antibodies and cytotoxicity. In addition we have a long track record of training students to prepare them for a carreer in how to an application essay 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 Infectious Diseases, National Institutes of Health, Bethesda, MD October 1989 - June 1993 U.S. Public Health Service, Research Associate (C.O.), Respiratory Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of brenner thesis Health, Bethesda, MD July 1993 - June 1994 U.S. Difference Essay Statement For College? Public Health Service, Clinical Associate, Clinical Center, National Institute of 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 brenner thesis Allergy and film resume cv 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 brenner Review Board Activities. 2009 - U.S. Write An Application Descriptive? Public Health Service Outstanding Service Medal 2009 - present Vaccine Production Development Team Scientific Advisory Board, University of brenner 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 Connors M. HLA B*5701 is highly associated with restriction of virus replication in essay for college a subgroup of 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. HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors. Nature Immunol 2002; 3(11); 1061-1068. Brenner Thesis? 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 HLA B*5701+ long-term nonprogressors and progressors to restrict HIV replication is an application essay descriptive, not caused by loss of recognition of autologous viral gag sequences.
J Virol 2003; 77(12); 6889-6898. Brenner? 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 recovered by exogenous IL-2. Gay Marriage Essay? 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 thesis 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. Lytic Granule Loading of CD8+ T-Cells is Required for HIV-Infected Cell Elimination Associated with Immune Control. 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 how to write 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 brenner thesis association with clinical variables. J Virol 2009 84(3): 1631-1636.
Doria-Rose NA and battle essay gettysburg 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. Brenner Thesis? Long-term nonprogressive disease among untreated HIV-infected individuals: clinical implications of understanding immune control of HIV. JAMA 2010 304:194-201. Battle Essay? [Redacted publication in press]
The research direction of the HIV-Specific Immunity Section of the brenner thesis Laboratory of Immunoregulation is focused upon mechanisms of immunity to HIV. The laboratory is and personal statement for college, staffed by PhD and MD scientists with extensive experience in the humoral or cellular immune response to HIV. Thesis? In addition we have close collaborations with investigators at the NIAID Vaccine Research Center in the area of structure-function relationships of HIV-specific antibodies. Causes Depression Essay? Our laboratory is well equipped with multi-laser flow cytometers, automated magnetic sorters, and imaging equipment to carry out brenner thesis, this project. Our laboratory is gettysburg, supported by the research budget of the thesis 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 AIDS Research for work on the humoral response to HIV. Positions and Employment. 1985 - 1992 Lecturer, Department of causes depression 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 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 Science 1998 - Member, American Society for Microbiology 1998 - Member, British Society for brenner, Immunology, UK 1998 - Member, Society for gay marriage discursive, General Microbiology, UK 2005 - Member of the Pasteur Institute Paris France Scientific Evaluation Committee. 2005 - Member of the brenner Vaccine Research Center (VRC) NIH Board of Scientific Councilors 2007 - Member of gettysburg 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 brenner thesis NIH study section for film resume cv, 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 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. (2010) SDF-1/CXCL12 production by mature dendritic cells inhibits the propagation of X4-tropic HIV-1 isolates at thesis the dendritic cell-T-cell infectious synapse. J Virol. 84:4341-51 Groot F, Welsch S and causes teenage depression Sattentau QJ. (2008).
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 brenner Davis DM (2008). Membrane nanotubes physically connect T cells over battle, long distances presenting a novel route for HIV-1 transmission. Brenner? 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. J. Virol.
81: 13916-13921. Jolly C, Mitar I and Sattentau QJ (2007). Requirement for film resume cv, an intact actin and tubulin cytoskeleton for efficient HIV-1 assembly and spread. J. Virol. 81: 5547-6 Jolly C and Sattentau QJ. Human Immunodeficiency virus type-1 virological synapse formation in T cells requires lipid raft integrity.
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. Brenner Thesis? 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 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 HIV-1 envelope glycoprotein antigenicity and immunogenicity. Battle? J. Brenner Thesis? 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 HIV-1 gp140 and influenza virus HA by a polyanionic carbomer. Vaccine 28: 2482-2489.
Zanetti G, Briggs JAG, Grunewald K, Sattentau QJ and Fuller SD. Depression Essay? SIV spike glycoprotein structure in brenner situ determined by cryo-electron tomography. Plos Pathogens August 2 (8): e83 Sheppard NC, Bates AC and Sattentau QJ (2007). A functional human IgM response to HIV-1 Env after immunization with NYVAC-HIV C. Essay Over? 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 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 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 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 brenner thesis Ab and use perforin to deliver granzymes which induce apoptosis in the target. We want to study ADCC in infected patients to understand the essay magnitude and characteristics of the best responses achieved by natural infection.
First, we will compare ADCC mediated by brenner thesis the sera of a cohort of patients using a granzyme B cytotoxicity assay developed in essay over 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 Fc type. Thesis? We will also evaluate whether ADCC is disparate from classical neutralization. Finally we will use microscopy to examine the write essay descriptive synapse between effectors, Abs, and targets. The outcome of this research will provide insight into brenner, 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. Essay And Personal? We hypothesize that variations in brenner thesis ADCC activity of sera are dictated by the amount, specificity, and subclass of HIV-specific antibodies. Aim 1 : Characterize the potency of sera of HIV-infected individuals in ADCC. In ADCC, Abs bind viral epitopes that are presented by gay marriage essay infected CD4+ T cells. Brenner Thesis? NKs expressing an Fc receptor bind the Fc domain of the over the chosen Ab and use perforin to deliver granzymes to the HIV-infected cell. Thesis? Subsequently, granzymes induce apoptosis within the cell. Our lab has developed a flow cytometric assay that measures granzyme B delivered to essay the chosen an HIV-infected CD4+ target T cell. We will classify ADCC by the percent of target cells receiving granzyme and 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 progression and viral loads to determine which contain Abs capable of mediating the brenner highest levels of film resume cv ADCC.
Compare the brenner thesis ADCC and neutralizing activity of patient sera. Aim 2 : Characterize the specificity and breadth of antibodies with ADCC activity. Our laboratory has panels of battle gettysburg NAbs derived from patients with known serum neutralizing or ADCC-mediating activity. Determine whether recognition of specific epitopes is required for ADCC. Define the breadth of the polyclonal sera by its ability to brenner thesis 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 structure and film resume cv function of the target-effector synapse.
Using both fixed and live cell laser scanning confocal microscopy (LSCM), transmission electron microscopy (TEM) and brenner thesis cryo-electron microscopy (cryo-EM) and tomography, we will examine the causes teenage depression essay synapse formed between NK and other cells with potential ADCC activity (macrophages and thesis neutrophils) and infected target cells. We will specifically investigate: The structure of a functional ADCC synapse. The kinetics of ADCC function in essay the chosen real time and its relation to antibody type and specificity. Brenner Thesis? A role for antibody-dependent cell-mediated phagocytosis (ADCP) in elimination of HIV-infected cells. d. Receptors and effector molecules central to ADCC activity against film resume cv, 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 brenner thesis, 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 the limitations of 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. Film Resume Cv? At present the only method for determining the potential benefits of a vaccine with regard to protection from 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 brenner permitting some estimation of discursive uk clinical efficacy prior to thesis a Phase III trial. 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 causes essay HIV have largely focused on CD8+ cytotoxic T lymphocytes (CTLs) or neutralizing antibodies (NAbs). In addition to neutralization, antibodies (Abs) may fight viral infections by antibody-dependent cell-mediated phagocytosis (ADCP) or by antibody-dependent cellular cytotoxicity (ADCC). In ADCC, Abs bind viral epitopes presented on thesis infected target cells and Fc? receptor-bearing effector cells such as natural killer cells (NKs) recognize and bind the and personal 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 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 macaques, suggesting that ADCC may be more important in preventing infection than neutralization or complement activation alone 4. Thesis? Prior to this study, it was widely accepted that infection of a single cell would lead to between and personal 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 concept that ADCC can eliminate lentivirus-infected cells in brenner vivo. In addition, some recent data in human efficacy trials has also greatly increased interest in ADCC as an important component of vaccine induced immunity to gettysburg HIV.
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. 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 brenner thesis, likely mediated through ADCC 5. Film Resume Cv? Our laboratory is thesis, part of a large international effort to causes teenage depression characterize ADCC antibodies from this trial in brenner order to determine whether there were higher ADCC-mediating antibodies in film resume cv uninfected vaccinees compared to 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 number, affinity, and brenner specificities of gay marriage discursive essay uk antibodies necessary to mediate ADCC remains poorly understood. Our laboratory has now developed assays that can accurately measure ADCC against HIV-infected cells. We also have assembled panels of monoclonal antibodies from individual patients that permit a characterization of individual antibodies that mediate HIV-specific ADCC. One of the brenner initial goals of this project was to adapt our current killing assay to provide a more robust assay for HIV-specific ADCC. Past studies of ADCC have been hampered by the availability of battle essay gettysburg assays that are only partially quantitative. There are four primary methods that people use to measure ADCC 6. The most prevalent is the chromium release assays (CRA), which is highly variable, does not specifically account for the mechanism of killing, and is insufficiently quantitative 7. The ADCVI assay incubates targets, serum, and effectors for 24 hours and the supernatant is applied to the B95-8 cell line for 5-7 days. The endpoint is reduction of viral infection of the B95-8 cells 8. This method measures inhibition of viral production and 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. The advantages of this assay are that multiple effector functions can be measured and all cells and Abs are from the same patient, but it is 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. While use of protein pulsed targets is thesis, a sensitive method, it likely places artificially high amounts of how to write descriptive 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 adaptation of an thesis assay for measuring the cytotoxic activity of CTLs developed in our lab11. This assay measures the essay over cleavage of a GrB substrate, and thesis eliminates background cell death using a Live/Dead stain to 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 film resume cv 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 brenner CD4 (PE-Cy7). A reduction in write an application essay the number of p24 stained cells is represented as Infected Cell Elimination (ICE) and 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. 12. In addition, because NK function is diminished in HIV-infected patients, we use the NK cells and CD4+ T cell targets from uninfected patients in our assay as a readout for the effectiveness of a given serum sample in mediating ADCC 13, 14. We observed variations in NKs from normal individuals in brenner thesis their ability to mediate ADCC and choose donors that provide optimal signal to noise ratio that we will use to compare the serum of gay marriage discursive essay uk HIV+ individuals (Figure 2). The targets used in this assay are likely closer to the in vivo situation given autologous HIV-infected targets are used in the place of antigen pulsed cell lines.
Other advantages include our assay’s ability to measure the mechanism of ADCC (granzyme delivery) and the outcome (death of brenner thesis 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 kill a cell 15, 16. We control for this by measuring the granzyme content of targets that are incubated only with effectors and sera from HIV-uninfected volunteers. For a positive control we are using a novel anti-CD3 Ab that will mediate ADCC to battle all CD3-bearing targets (Figure 3). Thesis? With this Ab we have already demonstrated (1) the sensitivity and dynamic range with which we are able to measure ADCC, (2) Abs mediate ADCC in a dose dependent manner, and (3) GrB delivery is proportional to cell death. Aim 1: Characterize the magnitude of ADCC in HIV infected individuals . Rational : There is considerable controversy regarding the magnitude of ADCC activity in between essay statement for college 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 brenner disease progression 19, 20.We will compare the serum of gay marriage discursive essay HIV+ individuals with various rates of brenner progression and statement viral loads to brenner thesis determine which contain Abs capable of film resume cv mediating the highest levels of ADCC. We will also compare the ADCC and neutralizing activity of patient serum to evaluate whether or not ADCC and thesis neutralization always occur together in polyclonal sera which is yet to be determined 21, 22. Methods : Over the past several years, in collaboration with the Vaccine Research Center (VRC) our laboratory has focused upon recruiting HIV-infected patients with broadly crossneutralizing antibodies. We have extensive clinical data and over the chosen 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. Our current knowledge attributes LTNP delayed progression to thesis 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 accomplishing this objective.
Aim 2: Characterize MAb from serum identified as having potent ADCC activity with regard to how to write essay specificity. Rational/Methods : HIV-infected cells express Envelope (Env) protein on their surface which is recognized by NAbs and presumably by ADCC-mediating Abs. We will use standard Nabs (including b12, 2F5, 2G12, 447-52D, 17B, and VRC01) and thesis patient derived MAbs to probe specificities required for ADCC. An ideal HIV vaccine would be able to protect against diverse virus strains so it is an application essay, important to determine whether Abs raised against one clade of virus would be able to mediate ADCC in CD4+ T cells infected by brenner thesis different clades. Essay Over The Chosen? We will use multiple strains of virus from clade A/E, B, and C to infect CD+ T cells and compare killing of target cells in thesis the presence of serum pooled from clade B HIV+ patients. IgG1 and IgG3 are the predominant IgG isotypes with roles in ADCC. It is possible that variations in ADCC activity of sera are mediated by essay variations in brenner thesis 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 film resume cv 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 brenner, the necessity of eliciting a specific class of over IgG via particular antigens and adjuvants. Potential Complications : We now have robust assays for brenner thesis, 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 write an application descriptive, important because it will help us define structural and kinetic parameters and will relate structure to brenner function.
Multiple mechanisms for cell-to-cell spread of over the chosen HIV have been described but few have described inhibition of viral transmission or targeted cell death 23. To date there has been no study using microscopy to investigate ADCC in brenner HIV using NKs or macrophages as effectors and CD4+ T cells as targets. The Chosen? 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. Brenner? With fluorescent microscopy they observed after 1 hour of incubation that 24% targets had formed conjugates with CD8+ T cells although many more cells had lysed. Causes Essay? At 2 hours 50 - 80% of targets were conjugated and undergoing lysis and by 24 hours all targets had been lysed. However, the brenner thesis bispecific antibody may not be representative of essay the chosen 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 thesis HIV infection.
They were the first to 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 film resume cv, 10-fold more efficient than free virus spread 26. To study the kinetics of ADCC in brenner thesis real time we will use time-lapse laser scanning confocal microscopy (time-lapse LSCM). Cell populations will be negatively selected from 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 film resume cv NKs to brenner evaluate ADCC; or neutrophils/monocytes to evaluate antibody-dependent cell-mediated phagocytosis (ADCP) and applied to poly-L-lysine coated cover slips. Cover slips will be fixed in paraformaldehyde, quenched with NH4Cl, permeabilized with Triton-X, and how to essay stained for granzyme B, IgG, CD4/CD16/CD14 with fluorescent probes. After mounting, images will be acquired every minute for brenner thesis, 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 film resume cv ADCC functional synapse. Thesis? 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. The Chosen? These experiments will be completed using the pathology department’s core bioimaging facility and I will take department’s Advanced Light Microscopy and Electron Microscopy course in thesis preparation for essay, this research. Expected Outcomes : We expect to elucidate the brenner kinetic and functional relationship between ADCC components and essay descriptive answer questions such as what density of brenner thesis Env epitopes are needed to recruit effectors, how many effectors are recruited per target. We do not foresee any difficulties in accomplishing this objective. The results of essay these studies will include novel MAb with possible therapeutic value; a new tool for the study of ADCC with potential utility for HIV vaccine trials; and increased understanding of basic HIV immunology. In the wake of the RV144 trial, ADCC has become a major focus in the field of HIV-specific immunity. We are very well positioned to brenner 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 both labs’ extensive experience in this area. Samples are collected under the NIAID IRB-approved protocol 02-I-0086. Protections for between, human subjects are in accordance with NIAID Division of Intramural Research policies.
Phlebotomy may cause some discomfort, and 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. In the course of 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 brenner thesis, within the safety guidelines for blood drawing practiced at the Clinical Center. Like standard phlebotomy, leukapheresis is between essay and personal, occasionally associated with local bleeding and bruising at the site of needle insertion.
Lightheadedness can also occur, and people faint on rare occasions. Occasional tingling in the arms and thesis legs can occur with the causes teenage procedure and can usually be relieved by chewing a calcium-rich tablet that the staff will provide. In addition, on thesis very rare occasions (less than 1 in every 1,000 times), malfunction of the leukapheresis machine can result in blood loss of up to 450 milliliters. Trained medical personnel who are equipped to deal with any of these potential problems will always be on hand during the procedure. Inclusion of Women and Minorities. Gender, Ethnicity and over Race Consideration. This study involves techniques and procedures that are currently approved for various indications. Male and female adult patients (18 years of age or older) will be enrolled without preference to thesis gender, race or ethnicity from the pool of patients that receive care in Clinics 8 at how to essay descriptive the NIH Clinical Center. Brenner Thesis? Patients will be recruited from outside the NIH community by advertisements posted in how to the Clinical Center, the NIAID web site, and brenner thesis advertised in other media. We will attempt to film resume cv facilitate minority recruitment using existing NIAID community outreach efforts involving local clinics in brenner the Washington, DC metropolitan area.
In adult HIV-infected patients planning to uk interrupt HAART, patients will be fully counseled prior to brenner thesis entry into the study as to the potential risks of discontinuing HAART therapy and the potential benefits of continuing HAART therapy, in the setting of 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 immunologic relapse and will be offered therapy, based upon essay gettysburg, the algorithm for brenner, safety outlined above. Target enrollment for battle essay, this study is 300 individuals and is currently ongoing. Inclusion of Children (and Pregnant Women) Inclusion of thesis Children and 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 teenage this trial, thereby children are not being denied the potential benefits of thesis a research intervention. We also do not have the uk historical research database and in vitro findings on HLA linkages with LTNP in the pediatric population to make valid comparisons within that cohort.
The potential risks of withdrawing therapy in minors have not been studied and therefore may present unknown additional risks to that study population. Comparable units specializing in brenner thesis pediatric HIV are available at the NIH to address this topic, should preliminary results from this study warrant further evaluation in the pediatric population. The safety of 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. The Chosen? Therefore, pregnant or nursing women will be excluded from thesis, this study. 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 reliable birth control for the duration of the 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 the chosen their focus on HIV immunology, vaccine design, and brenner their expertise in basic immunology techniques, flow cytometry, and microscopy. I initiated contact between the 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 essay gettysburg 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. Brenner? We also conduct quarterly phone conferences with Dr. Sattentau, maintain a regular email correspondence, and meet at conferences. 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 this field.
I decided to join the an application NIH/Oxford/ Cambridge Scholars Program to complete my dissertation research because it would provide me access to a more extensive network of brenner thesis scientists than Columbia could. Oxford has a particularly strong network of film resume cv 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 accelerated 1-day to 1-week courses that allow me to attain skills quickly and immediately implement them into my research. In addition, the brenner thesis NIH/Oxford/Cambridge Scholars program provides funding for students to take courses offered by an application essay 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 thesis take courses that will help me towards my goal as in infectious disease investigator such as the 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 gay marriage Oxford and identified Mark Connors and Quentin Sattentau as potential mentors because I wanted to 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 thesis adjuvants to stimulate systemic and how to an application essay descriptive mucosal immunity. Through my search at the NIH I identified Mark Connors as a potential collaborator though he and Quentin had never collaborated before. Brenner? I believed Dr. 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 between and personal statement LTNPs would provide ready access to samples to study many facets of HIV infection. Finally, I believe Dr. Sattentau’s approach to research as a PhD and brenner thesis Dr.
Connors’ as an film resume cv MD will teach me to think about brenner, 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 battle research as outlined in NOT-OD-10- 019. As an thesis undergraduate at UMBC I took a semester-long course entitled “Ethics/Integrity in how to write an application essay descriptive Scientific Research” which first help me to brenner understand the responsibility scientists have to one another and medical community honestly share information. Write An Application? As a Columbia medical student, I have taken the Hippocratic Oath to thesis guide my patient care and I am expected to adhere to the code of ethics as outlined in how to student handbook. Upon joining the NIH I took an thesis online ethics course and will continue to take refresher courses annually. Essay? At Oxford I will continue my ethics training by taking the required “Ethics: Introduction to brenner Research Ethics”.
Since I will have access to sensitive patient data it is essential that I maintain the confidentiality of these individuals. When I started research at write an application essay NIH I participated in a patient confidentiality seminar. Thesis? Oxford offers an essay “Ethics: Confidentiality” course in which I will enroll to better my further my understanding and ability to brenner thesis maintain ethical practices with regards to research. As a physician, I hope to alleviate an individual’s immediate suffering; and essay uk as a scientist I hope to brenner contribute to long-term solutions that can prevent suffering. To work most effectively at the interface of medicine and science, I have endeavored to essay earn an MD/PhD.
I believe that the 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 enzyme that maintains healthy chromosome length. When telomerase is upregulated, as it is in 90% of carcinomas, cells can propagate indefinitely. When telomerase levels are halved, a bone-marrow failure disease called Dyskeratosis Congenita (DC) results. While looking at brenner 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 how to telomerase grew slowly. Secondly, these cells had abnormal morphologies, as do tumor cells. Brenner? 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. Research in biochemistry affords many new advances in 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 film resume cv the field of 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 thesis take longer for difference and personal statement for college, 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 brenner opportunity to an application 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 brenner thesis use flow cytometry. I discuss my research progress frequently during the how to an application essay descriptive week with Dr. Connors. We also have phone conferences and meet with Dr.
Sattentau at numerous conferences throughout the year. Writing Skills : When I entered the thesis 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 between 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). Thesis? I will also complete the Scientific Writing from teenage depression, a Reader’s Perspective seminar. Discipline specific learning : I completed the 3-day “Vaccines: Development and 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 brenner bedside clinical training : I will attend the how to an application essay Clinical Research Training Program (CRTP) weekly rounds. I will also have the opportunity to be mentored by an infectious disease clinician. Presentations : I will continue to annually attend and present at brenner thesis pertinent Keystone Symposia and the Annual AIDS Vaccine conference. I have also had opportunities to present posters at gay marriage the NIH/Oxford Cambridge Scholars Program Colloquium and thesis the Oxford Pathology Graduate Student Symposium. I have given a talk to my graduate program journal club and discursive 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 thesis government/academic research, the gay marriage essay uk pharmaceutical industry, and finance speak with us about their career. I also attended NIAID Fellows retreat that focused on brenner thesis 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 over studying HIV infection. I will have weekly meetings to discuss my research progress. Brenner? We will have phone conferences and meet with Dr. Connors at various conferences throughout the year. Write Descriptive? I have also been assigned a graduate advisor within the pathology department but not in brenner 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 my research to 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 essay 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 brenner thesis 4-day Oxford GRADschool, a personal development course. Teaching : I will seek to be an undergraduate lab instructor and 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 America that introduced me to molecular biology and the exciting race to sequence the human genome. That summer, I learned much more than how to run a gel; I learned to read and comprehend primary research articles and how to design experiments. Film Resume Cv? Because of brenner my accomplishments that summer, I was invited to causes essay participate in an extension of the thesis Gene Search Program during my 12th grade year. This program inspired me to pursue a career in biomedical research because I began to write an application descriptive understand how the principles I was learning in brenner school fostered scientific discovery. As a high school senior, I worked with Dr. William Winter at Howard University School of Medicine to film resume cv investigate pathways that regulate 2,3-diphosphoglycerate (2,3-DPG) levels in red blood cells (RBC). 2,3-DPG lowers the affinity of hemoglobin for thesis, oxygen, thereby facilitating oxygen release to tissues. Patients suffering with sickle cell anemia have high levels of 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. Write An Application Essay? To test this idea, we indirectly measured 2,3-DPG levels by brenner using spectrophotometry to measure a by-product of the 2,3-DPG pathway. An exciting therapeutic prospect of teenage essay our research is that an antagonist of the A3 receptor may prevent the thesis accumulation of 2,3-DPG and RBC sickling in patients with sickle cell anemia. I documented this work in a five-chapter thesis, in battle gettysburg 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 key to developing gene and antiviral therapies.
MuLV is brenner thesis, similar to HIV in that it is a retrovirus that packages two copies of its RNA genome. Packaging of over 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 brenner thesis Psi-site. Essay? Previous work in the Summers lab suggested a riboswitch mechanism for MLV genome packaging, where, in thesis monomeric RNA, Psi-site UCUG segments capable of teenage depression essay binding NC are sequestered by base pairing, but upon brenner thesis, dimerization, become exposed to bind NC. Film Resume Cv? 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 enhanced in short RNAs containing terminal phosphates, and 3) binding affinity varies by more than one order of magnitude depending on brenner which three nucleotides lie upstream of the guanosine. The paper I co-authored (Dey, A., et. al., 2005) extends an established model for genome recognition, in film resume cv which the brenner thesis 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 the dimeric RNA. I presented this research at the 2004 ABRCMS and at multiple UMBC symposiums. I continued to how to an application essay investigate potential dimerization and NC-binding regions of the brenner thesis Psi-site using native and mutant MuLV RNA segments in gel-shift assays.
As expected from gettysburg, our riboswitch hypothesis, we observed NC binding preferentially to RNA dimers which was also confirmed by equilibrium dialysis. Most recently our lab published the NMR structure of brenner thesis this dimer (Miyazaki, Y., et al., 2010). During the summer of 2005 I participated in the Weill Cornell/Rockefeller/Sloan Kettering Gateways to the Laboratory Program. I worked with Dr. Nikola Pavletich toward solving the crystal structure of the the chosen 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 brenner thesis UV-light and develop skin cancer during childhood.
I identified DNA substrates to be used in crystallization trials by HPLC-purifying DNA, performing gel-shift assays, and setting up crystal trays. I presented this work in film resume cv 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 thesis two common human ailments—cancer and aging. Causes Teenage Depression Essay? To study how and where in the cell telomerase is assembled from brenner, its RNA and protein components, we used the causes budding yeast Saccharomyces cerevisiae as a model organism. 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 brenner TLC1 is exported to the cytoplasm where it associates with Sm proteins.
Mtr10p then plays a role in between essay and personal statement importing the TLC1-Sm complex back into the nucleus, where the thesis telomerase holoenzyme is causes teenage essay, 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 lab of Mark Connors where I screened patient sera for breadth and potency of thesis neutralizing Abs against 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 lead to my proposed project of 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 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 an application improve health care through innovative research. [Redacted from sample.] QUENTIN SATTENTAU MENTOR STATEMENT. [Redacted from brenner thesis, sample.] [Our Web version of this sample application can't reproduce the layout of the essay descriptive 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 brenner thesis investigate antibody-dependent cellular cytotoxicity (ADCC) in HIV-infected patients do determine the extent of protection that ADCC provides. The reviewers noted that the candidate is outstanding, with a strong record of research training and how to accomplishment. The candidate appears to be highly motivated. Brenner? Her sponsors, at both institutions, are well qualified to provide the necessary training and the letters of recommendation were uniformly laudatory.
Minor weaknesses of the difference and personal application included the brenner thesis ambitious research plan to be accomplished in two years, the risk of conducting the uk research at two sites, and 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 brenner ensuring that the candidate maintains her potential to become an causes essay independent clinical researcher. DESCRIPTION (provided by applicant): 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.
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 thesis 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 deliver granzymes which induce apoptosis in the target.
We want to study ADCC in infected patients to understand the causes depression essay magnitude and 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 most ADCC, generate monoclonal Abs (mAbs), and characterize the mAbs based on epitope specificity, affinity, potency, breadth, IgG isotype, and Fc type. We will also evaluate whether ADCC is disparate from classical neutralization. Brenner? 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 essay over the chosen 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 sera are dictated by brenner the amount, specificity, and subclass of HIV-specific antibodies. Aim 1: Characterize the potency of sera of HIV-infected individuals in ADCC. Aim 2: Characterize the specificity and breadth of antibodies with ADCC activity. How To An Application? Aim 3: Characterize the structure and function of the 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. Understanding the role of antibody-dependent cellular cytotoxicity (ADCC) in brenner thesis 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 defining new goals for the development of HIV vaccines and therapeutics. Fellowship Applicant: 1.
Sponsors, Collaborators, and 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. Partnership Training Program and causes depression essay is a participant in the NIH/Oxford/Cambridge Scholars Program, which promotes joint research in brenner an NIH laboratory and in a university research lab. Ultimately, she will receive her Ph.D. from Oxford University and write an application descriptive complete her medical training at Columbia University. The applicant is highly recommended by brenner thesis previous research mentors and has an film resume cv outstanding academic record. Her research experience, which includes four years of thesis undergraduate research, is matched by causes depression essay her productivity; she is brenner, a contributing author on and personal two published papers and has presented her work at numerous scientific venues. Thesis? The research plan, which derives directly from the expertise and interests of the 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.
These studies will be significant for their basic science and translational value. The training plan is unique in that training and research will be accomplished in two separate laboratories of the how to write an application sponsor and co-sponsor. This proposal outlines an excellent training opportunity that will greatly benefit the applicant and her potential for establishing an independent research career. The applicant, who is currently enrolled in an M.D./Ph.D. Brenner? training program, is described in descriptive three strong letters of brenner 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. Film Resume Cv? The applicant has four years of undergraduate research experience, which involved work with the Moloney Murine Leukemia Virus, and 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. Brenner Thesis? Through her prior research experience, the applicant has been included as a contributing author on gay marriage essay two published papers and 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 a dialog initiated by brenner thesis 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 the chosen 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 the NIH. The co-sponsor is also a productive researcher with a consistent record of support for studies related to HIV/AIDS. The research interests and brenner expertise of the sponsor and co-sponsor will provide excellent support for the applicant’s research and training.
The expertise of the difference between for college co-sponsor will be particularly relevant to studies outlined in thesis Aim 3. Uk? The sponsor has trained an average of 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 brenner the sponsor’s lab, and four Ph.D. trainees in the co-sponsor’s laboratory. The latter trainees will overlap with the applicant for film resume cv, one year or more. Thesis? These interactions will enrich the applicant’s training. The research plan is built on studies of antibody-dependent cellular cytotoxicity in HIV-1-infected individuals. Experiments will examine the potency of sera of film resume cv HIV-1-infected individuals in ADCC (Aim 1), the specificity and breadth of antibodies with ADCC activity (Aim 2), and the structure/function of the target-effector synapse that mediates ADCC.
The central feature of the proposed research is a novel and quantitative ADCC assay (developed in brenner thesis the sponsor’s lab) that offers significant improvements over other ADCC assays. Results generated from experiments in Aims 1 and 2 will have both basic science and translational value, while results from between and personal, Aim 3 experiments will provide basic information about the mechanisms of ADCC. The applicant and brenner sponsors are well positioned to perform these studies, since the patient populations and study procedures are already in the chosen place. Thesis? The applicant is gay marriage uk, participating in brenner the NIH/Oxford/Cambridge Scholars Program, which promotes research with a mentor at the NIH and another mentor at a university. Consistent with the Scholars Program, the essay research training plan includes studies and brenner training in difference between essay and personal for college year 1 in the sponsor’s lab at the NIH, continued studies and brenner thesis training in year 2 in the co-sponsor’s lab at Oxford, and years 3 and 4 in for college 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 thesis opportunities for presentation of results and film resume cv teaching. Training at the NIH (sponsor) will be a continuation of the brenner thesis current laboratory work, with increased emphasis on discursive 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 given as 300 HIV-1-infected individuals, the experimental plan does not provide details regarding the scope of studies in Aim 1. Correlates of ADCC to be studied in Aim 1 (“rates of progression and viral loads”) were not described in sufficient detail. How will rates of progression be measured? Will viral load be documented on thesis a continuous scale or will patient viral loads be stratified?
An explanation of how the results of how to write Aim 1 experiments will be used to guide the thesis 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 essay applicant to develop an brenner independent and productive research career. 5. Institutional Environment Commitment to Training: The resources and facilities at film resume cv both institutions will provide outstanding environments for training and research. A more detailed plan regarding the coordination of training plans between the sponsor and co-sponsor would be valuable, considering the distance and time difference between the two performance sites. Training in the Responsible Conduct of Research:
Comments on Format (Required): The description of RCR training is brief and does not provide a detailed plan for formal training. However, enrollment in two formal courses at Oxford (both focused on ethics) is mentioned. Comments on Subject Matter (Required): Training courses and certifications at the NIH and brenner Oxford should provide information on relevant subjects. Comments on Faculty Participation (Required): Faculty participation could not be evaluated from the description of 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 battle gettysburg, 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 both are actively involved in brenner thesis the HIV arena. The primary goal of this project is to characterize antibodies that mediate antibody-dependant cellular cytotoxicity (ADCC). Teenage? 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 brenner specificity and breadth of film resume cv antibodies with ADCC activity (Aim 1 and thesis 2).
The third Aim to characterize the film resume cv structure and function of the target-effector synapse will be carried out at Oxford under the guidance of Dr. Sattentau. This aim will use fixed and live cell laser scanning confocal microscopy and thesis TEM to examine the write an application essay descriptive samples between NK and other cells with ADCC activity. If the applicant is thesis, successful the data from essay and personal for college, this project will be highly important for brenner thesis, HIV vaccine development. Difference And Personal Statement For College? The research project however is quite ambitious and no timeline is given. It appears that the brenner applicant plan to spend 1 more year in uk 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 brenner 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 essay, of the brenner thesis 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 an application essay UMBC she was a member of the Meyerhoff Scholars Program funded by the HHMI. The applicant has coauthored 2 papers and is the first author on 8 posters and 1 oral presentation. The applicant has extremely strong letters of recommendations, one of brenner 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. An Application Descriptive? 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 brenner Oxford, is equally meritorious with over 151 published manuscripts and solid funding record. Dr. Sattentau, also has a established track record of training PhD student (n=9) and causes teenage depression post-docs Both sponsors have well established complementary HIV research programs that will support the applicants proposed research project. The planned research, if successful, could provide important information about of the role of brenner thesis ADCC in HIV infection. The project is uk, well outlined and brenner thesis there are sufficient preliminary data to support the feasibility of the project.
The plan is to 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. Between? Using this technique the applicant plans to characterize the potency of sera from subjects with different rates of disease progression, characterize the brenner thesis 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 battle gettysburg examine the structure and function of the target-effector synapse. This work will be done under the guidance of thesis Dr. Essay Over The Chosen? Sattentau who is an expert in studying the virologic synapses. This is a highly ambitious grant.
It may be difficult for brenner, the applicant to film resume cv finish all the brenner thesis proposed work especially the film resume cv work proposed in Aim 3. The applicant is calling for brenner thesis, 300 subjects but no power calculation is film resume cv, shown to brenner 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 write an application class room training of new personnel) and discipline specific learning (i.e. in house courses and seminar series, lab meetings). Letters describing each institution’s role in thesis 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. Write An Application Descriptive? 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 the NIH for thesis, 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. 2 years). 5. Institutional Environment Commitment to Training: The work will be conducted at the NIH/NIAID and University of Oxford. Both institutions are of the highest caliber with access to all the required resources. Oxford has a program in battle essay place for graduate students to take accelerated courses and the NIH Foundation for brenner thesis, Advanced Education in the Sciences also has specialized courses that will facility the applicants goal to become an infectious disease investigator. Training in the Responsible Conduct of Research: Comments on Format (Required): On line ethics course at the NIH and formal classroom course at Oxford. Comments on Subject Matter (Required):
Applicant states they will follow principle of gettysburg research outline in NOT-OD-1-019. The applicant has taken semester long course on brenner Ethics/Integrity in Scientific research. Difference Essay And Personal Statement For College? The applicant took another Ethic course upon entering the brenner thesis NIH. Oxford offers a similar course. Comments on film resume cv 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 brenner Training: 1. Overall Impact/Merit : This proposal comes from an excellent candidate who is part of the NIH/Oxford/Cambridge Scholars program, carrying out discursive uk, her PhD research under the guidance of two excellent researchers and mentors, Drs.
Connors (NIH) and Satentau (Oxford) and will complete her MD studies at Columbia. The primary hypothesis of brenner this proposal is essay, that ADCC activity levels in sera are dictated by the amount, specificity, and subclass of HIV-specific Abs. Thesis? This represents a highly relevant area of research that will be tackled through 3 straightforward and gay marriage discursive well-planned aims – (i) characterize the potency of sera from individuals at brenner different stages of HIV infection in ADCC (comparing to causes teenage essay clinical status and Ab neutralization), (ii) characterize the thesis specificity and an application breadth of thesis Abs mediating ADCC (comparing the battle sera to panels of known neutralizing Abs), and (iii) characterize the ADCC synapse. This will involve state-of-art approaches established in brenner thesis the sponsors’ labs, allowing the applicant an excellent chance to perform this research. And Personal Statement For College? It is a clear and well-written proposal detailing a strategy to carry out relevant research in brenner 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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An anti-uniform essay, covering several points on why uniforms should not be implemented into a school atmosphere. Essay by poisonenvy , Junior High, 9th grade , A+ , December 2002. Why do many schools adopt uniforms into their schools? There is brenner thesis, even mention of battle essay gettysburg, some public schools adopting uniforms into their school atmosphere. Brenner Thesis? Obviously, there are some pros and cons in this issue, and both must be weighed cautiously before arriving at a decision. I think that schools should keep their students in mind above all. If they don't, then whichever choice they make in difference essay statement for college, this debate will be a negative one. Is it really fair to thesis think that the outward appearance of the battle essay, students will change anything?
That if all students are uniform there will some kind of change? Isn't that idea a little superficial? In my opinion, promoting vanity won't help any school much, if at all. Brenner? In some cases, it may even make things worse. Essay Uk? Some parents complain about brenner, buying clothes for their children, and the great expenses that it involves. Some parents seem to think that if the students all look a like, the students will therefore be more able to concentrate on their education.
Students are young people, and mostly, it's normal for them to gay marriage be concerned about style and general outward appearance. Stripping away almost all outward individuality will not help matters. I think that there are more important issues than what kids today are wearing. If it's modest, if it covers up enough, if it doesn't infringe on anyone's rights, well then why shouldn't kids today exercise their freedom of dress? Freedom of dress. It's true, freedom of dress is an brenner important thing.
How you dress is an expression of who you are. Think about it this way, say the uniforms that are chosen, assuming of course the write an application essay descriptive, school does approve it, are against a particular teens fashion tastes. The teen will then proceed to say statements such as yuck, I wouldn't be. An anti-uniform essay, covering several points on why uniforms should not be implemented into a school atmosphere.. (2002, December 16). Thesis? In WriteWork.com. Retrieved 01:09, October 03, 2017, from http://www.writework.com/essay/anti-uniform-essay-covering-several-points-why-uniforms-sh.
WriteWork contributors. An anti-uniform essay, covering several points on why uniforms should not be implemented into a school atmosphere. WriteWork.com. WriteWork.com, 16 December, 2002. Web. 03 Oct. Between And Personal Statement For College? 2017. WriteWork contributors, An anti-uniform essay, covering several points on why uniforms should not be implemented into a school atmosphere., WriteWork.com, http://www.writework.com/essay/anti-uniform-essay-covering-several-points-why-uniforms-sh (accessed October 03, 2017) Reviews of: An anti-uniform essay, covering several points on why uniforms should not be implemented into a school atmosphere. : you need to view both sides of the fence though. Brenner Thesis? like gangs wearing gang colors and starting fights but i do agree with your view. good job. 4 out of how to write essay, 4 people found this comment useful. Brenner Thesis? . clothes.
If you do not achieve a college diploma you might not appear in society as well put together as you would like. Essay Over The Chosen? It all really boils down to brenner thesis what you want out of essay over the chosen, life. Everyone suffers through the trials and . 2 pages 291 Feb/1996 3.9. . students learn about brenner, music, have physical training, and learn to read and write. Gettysburg? Later on in the Greek society, poor and rich students all went to school and all men soon learned to read and write. There are many differences in brenner thesis, the two different civilizations and . 2 pages 176 3 Apr/1997 3.9. Explain why cultural diversity is important in a college education. . school didn't disrupt education, rather enforced lessons often reviewed over gay marriage essay, fried chicken and potatoes.
I cried once in my sophomore history class. The girl in front of me sang and preached that life was just that way, no one . , and exchanged math notes with a fascinating foreign exchange student. . 3 pages 324 1 Jan/1996 4.8. Private Education in thesis, relation to book: 'Private schools: Essential or undemocratic' by Nelson, J.L., Carlson, K., Palonsky, S.B. . Film Resume Cv? schools are an unnecessary burden and expense to the public. Private schools have the thesis, tendency to tarnish the essay, image and brenner reputations of good public schools. Essay And Personal? Magnet, or theme-oriented, schools are public schools that provide various, specific programs of study for thesis, their students . 2 pages 89 Sep/1995 4.2.
A WORLD OF DREAMS. Achieving your dreams. . , and my performance in school. That is why I have made up my mind to never compromise my life or values due to teenage essay peer pressure. There is brenner thesis, only one way for causes teenage depression essay, me to get where I'm going and that is through hard word and . 2 pages 124 Mar/1997 3.7. Good news: you can turn to other's writing help.
WriteWork has over 100,000 sample papers Prof. Jacob Leland, Phd. I turned what i thought was a C+ paper into an A- Dawn S., college student. CNN WIRED EveningTimes Sony NPR Independent The Boston Globe The Virginian Pilot. Rutgers University Marist College Boston College Boston University University of Colorado University of Maryland University of Phoenix New York University Indiana University Columbia University Miami Dade College University of Missouri. . the country. The United Nations Development Program (UNDP) estimates that India . 5 pages 16 May/2009 0.0. Task II Essay: Why School should start later? . known fact by students that they are already asked to wake up early enough, but waking up . 2 pages 25 Nov/2006 0.0.
Paulo Freire's The Banking Concept of brenner, Education . Paulo Freire is saying that the teacher -student relationship is poor because of the fact that the . 5 pages 36 Feb/2009 3.0. Skooluniforms. Gee jou opinie oor die voor - en nadele van gereguleerde skooldrag. Die onderwerp van skooluniforms is film resume cv, 'n belangrike onderwerp vir baie leerlinge en hulle ouers. 'n . 2 pages 24 May/2005 5.0. Brenner? . the spirit of the gay marriage discursive, United Nations quest for harmony in international relations. The .
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comparasion essays You’re looking for a great compare and contrast essay topic to kick start your assignment. How can you choose an interesting topic that’s simultaneously narrow yet broad enough to thesis, provide you with plenty of gay marriage discursive essay, great material? In this blog post, I’ll give you 70 compare and contrast essay topics. I’ve also included links to sample essays for even more inspiration. With many of these topics, I’ll also give you some basic compare and contrast points to get your ideas going. Note that my points are pretty general. When you write your compare and contrast essay, you’ll want to dig deep, do your research, and find the most interesting facts. Let’s get started! Compare and Contrast Essay Topics: Influential People. People are the thesis, definition of unique—no two are exactly alike.
The challenge is to find the similarities between two individuals, even when they seem to have nothing in common. Comparing two people from gay marriage discursive essay a similar background is brenner, pretty easy. But surprising comparisons—such as those between fictional characters and real-life people or between people from different epochs—can lead to essay over, the most interesting essays. When you successfully make those unlikely connections, readers will be awestruck by your sheer brilliance. 1. Mahatma Gandhi vs. Brenner? Osama Bin Laden. Mahatma Gandhi and Osama Bin Laden were both extremely influential figures who successfully motivated thousands of people to depression, act on behalf of thesis, their visions. Both leaders were killed by their opposition.
Gandhi was a pacifist and a bastion of peace and compassion. He fought for freedom and civil rights. Bin Laden was an the chosen, extreme militant and a bastion of war and brenner intolerance. He fought for the implementation of extreme religious propaganda. 2. Edward Snowden vs. Julius Caesar. Both Edward Snowden and Julius Caesar played an instrumental role in film resume cv, the inevitable demise of the powerful institutions in which they functioned—Snowden the 21st century United States of America and Caesar the Roman Republic. Snowden fights for the rights of the people, while Caesar fought against thesis the people in his quest for descriptive, ultimate power. Speaking of Romans: The Roman and Han empires make for an interesting comparison. Brenner? Even though the two nations were separated by time and geography, they experienced striking similarities in technological, political, and economic advances. OJ Simpson and Tom Robinson were both black men who stood accused of violence against white women.
Both men were convicted for these crimes. Their convictions left behind a debate as to whether the men were actually brought to justice or rather were victims of racial injustice. Tom Robinson is a fictional character from the book To Kill a Mockingbird . OJ Simpson is a real-life former NFL player. Battle Gettysburg? Tom Robinson was sentenced to death, while OJ Simpson received a prison sentence. 4. Harriet Jacobs vs. Frederick Douglass.
Harriet Jacobs and Frederick Douglass were former slaves who became abolitionists. Both Jacobs and Douglass wrote profound autobiographical accounts of brenner, their lives as slaves that helped form the argument against causes depression essay slavery. Harriet Jacobs wrote about the struggles and hardships unique to brenner, women in slavery, such as sexual abuse. Essay? Frederick Douglass wrote about the struggles and hardships specific to men in slavery, such as emasculation. Thesis? Douglass went on to become a well-known orator and essay gettysburg ran for vice president on the Equal Party Ticket. Jacobs remained an important but relatively unrecognized figure in the abolitionist movement. Both Hitler and Stalin were dictators who achieved a high level of power during WWI and WWII. Brenner Thesis? Both men were behind innumerable human atrocities that killed millions of innocent people. Hitler was the leader of the Nazi Party in Germany. Stalin was the leader of the Communist Party in the Soviet Union. Nazism, by definition, is opposed to communism.
Maya Angelou and Alice Walker are both well-known African American authors. Teenage? They are credited with contributing important fictional and non-fictional texts on the issues surrounding what it means to be black in the United States. They are both inspirational political and civil rights activists. They are both recipients of the Pulitzer Prize. In addition to writing, Angelou is also known for her work as an actress and film and television producer. Brenner? Even though they addressed similar topics in their writings, the two authors wrote in very different styles—each with her own unique voice.
Hobbes and Locke were both 17 th century English philosophers. They were both interested in exploring political philosophy. Both men, for instance, talked about a state of nature—the idea of man existing without government—and the dangers of causes essay, such a state (though that’s where their similarities largely ended on the topic). Hobbes and Locke disagreed on a number of issues. Thesis? For example, Hobbes believed that man is by nature a social animal, while Locke believed the film resume cv, opposite. Hobbes believed that man has an intrinsic understanding of the difference between right and wrong. Thesis? Locke believed that man only understands the difference between right and wrong when an authority, such as the law or God, enforces it.
8. Ellen DeGeneres vs. Difference Essay For College? Oprah Winfrey. Ellen DeGeneres and Oprah Winfrey are both American television personalities who have hosted their own daytime talk shows. Both women have been extremely successful in their careers. As a comedienne, DeGeneres relies on thesis witty humor and sarcastic criticism to convey her messaging, while the more serious Winfrey relies on inspiration, insights, and aha moments. “My grandmother started walking five miles a day when she was sixty. She’s ninety-seven now, and we don’t know where the hell she is.” – Ellen DeGeneres. 9. Write Essay Descriptive? Booker T. Washington vs. W.E.B. DuBois.
Booker T. Washington and W.E.B. DuBois were both early 20 th century civil rights activists. Thesis? They were both great leaders of the black community. Both men were also accomplished scholars. Washington and DuBois disagreed on how to go about achieving racial equality. Washington believed that African Americans should earn equality through self-help and hard work. Essay The Chosen? DuBois, conversely, believed that African Americans needed to become better educated and more politically active. Plato and Socrates were both ancient Greek philosophers.
They are considered to be the founders of Western philosophy. Both men also founded a school. Socrates was Plato’s teacher and mentor. Socrates expounded on the wisdom of “I know that I know nothing.” Plato philosophized that the world of ideas was the only constant and that the world of senses is changeable. Adolf Hitler and Regina George both can be considered dictators in their own right. Brenner Thesis? Both Hitler and film resume cv George believed that people with blonde hair, blue eyes, and other Aryan features were somehow better than other people.
Adolf Hitler was a real person, dictator, and founder of Nazism in Germany. He was responsible for countless human atrocities, including the murder of over 6 million Jews. Thesis? Regina George is causes teenage, a fictional character from the brenner thesis, 2004 movie Mean Girls . George’s biggest human atrocity is the creation of the Burn Book , a book that libels the other students in school. Both Pope Francis and Macklemore believe in love, equality, and showing compassion to others. Both are cultural icons. Both men have the ability to reach out to and speak to the masses.
Pope Francis is the leader of the Catholic Church. Macklemore is an American entertainer and hip-hop rapper. Macklemore “wears your grandad’s clothes,” while Pope Francis is old enough to be your grandad. 13. Battle Essay? Lin-Manual Miranda vs. William Shakespeare. Both playwrights have changed the face of theater forever. Both playwrights have been criticized for creating historically inaccurate works.
Both writers make political and social commentary in their plays. Shakespeare’s plays were not musicals (though they often contained musical components). Miranda’s most famous play, Hamilton , is a wildly successful musical. Brenner? Shakespeare lived and wrote in the 16th century, while Miranda is over the chosen, a contemporary playwright. Reagan and Trump were both television and media stars before becoming president. Brenner? When they were first elected, many people feared that neither one of these men would be strong or effective leaders. When Reagan took office, interest rates and inflation were high. Trump, on essay over the chosen the other hand, entered office with historically low inflation and interest rates. Many people believed Reagan understood the problems with government and believed he was willing to work with citizens to help solve problems. Brenner Thesis? Trump has claimed that he alone will be able to solve problems. Compare and Contrast Essay Topics: History.
17. Medicine in Ancient Greece vs. medicine in Ancient China. 18. Media coverage of past wars vs. media coverage of current wars. Compare and Contrast Essay Topics: Religion. When you set out to compare and contrast world religions, you may feel like you have fallen down a rabbit hole. Depression? A student I know once wrote an essay comparing Jesus Christ and Snow White—talk about falling down a rabbit hole! What’s more, the crossovers between two opposing religions can be surprising.
Protestants were originally a part of the Catholic Church. So they still believe that Jesus is the savior and that he was crucified and brenner thesis rose from the dead to save humanity. Among their many differences, Catholics believe in Holy Water, purgatory, and that those wafers you eat at gay marriage essay, mass are actually, literally the body of Christ. Protestants don’t believe in any of that. (While protestants do take communion, they don’t think the wafers are really a piece of flesh.) Catholics have nuns, priests, and brenner thesis a pope. Protestants don’t. 22. Theravada vs. Mahayana Buddhism. Both Theravada and Mahayana Buddhism follow Dharma, the film resume cv, teachings of brenner thesis, Buddha.
Both reject the notion of a god or gods (they are nontheistic ). Both believe theistic religions are misguided. Theravada and Mahayana Buddhism have some basic philosophical differences. For example, Theravada Buddhists believe that Buddha died, leaving his teachings behind. Mahayana Buddhists believe that Buddha lives on in various incarnations. Judaism and Christianity are both monotheistic religions that teach about one almighty God.
Both are Abrahamic religions. Both religions teach the Old Testament. Both believe in angels, demons, and spirits as spiritual beings. Christianity teaches that Jesus Christ was the messiah and that he will return to Earth one day. Christians believe that Jesus died for the sins of humankind. Judaism teaches that Jesus was a teacher and a prophet of God, but not God himself. Judaism also rejects the notion of Jesus’s sacrifice. 24.
Religious mindset vs. cult following. Both organized religions and cults seek spiritual enlightenment and follow the teachings of a leader. Both have members with varying levels of practice and extremism. Cults are more likely to attempt to extort money from their followers. Cults are also more likely than religions to use mind-control to write essay descriptive, force members into following the teachings of the cult. Jesus Christ and brenner Buddha were both spiritual leaders. Both were teachers and tutors during their time on Earth. Both were miraculously conceived, performed miracles, and were tempted but overcame the devil. Though Jesus performed several notable miracles, Buddha did not. Buddha believed that he lived his life in gay marriage discursive, search of the truth, while Jesus believed he was the brenner, truth.
Compare and Contrast Essay Topics: Countries and Politics. Compare and Contrast Essay Topics: Education. You can compare and contrast different facets of education until you are as blue as a Smurf. To succeed, you’re better served by an application descriptive pitting two very specific elements of thesis, education against each other. The trick is to film resume cv, narrow your angle down to a tight focus while leaving room to write enough compelling points to describe the brenner, differences and similarities. 33.
Private vs. public universities. Both private and public universities offer a range of film resume cv, academic courses and opportunities. Brenner? Both allow students to earn a bachelor’s, master’s, or doctorate degree. Private universities are typically more expensive. The College Board reports that for the 2013-2014 school year, private universities cost over $30,000 for one year of tuition, while public universities cost just over $8,000 for in-state and $22,000 for out-of-state tuition. Battle? However, private institutions are known to offer better financial aid options. Both small and large universities can provide students with the opportunities to achieve educational goals. Both offer bachelor’s degrees. (We’re not comparing the size of thesis, their parties here…but you could!) Small universities offer individualized majors, smaller class sizes, and hands-on learning opportunities.
Large universities offer state-of-the art research facilities, a wider range of academic programs, and more student clubs and events. High school is a stepping stone to difference between essay statement, attending college. Students need to brenner thesis, successfully complete the curriculum of both educational institutions in causes depression essay, order to advance in many careers. Both institutions employ instructors to teach coursework. Both require students to refer to textbooks. Both require substantial homework. High school allows for fewer academic choices. Students are typically limited to brenner thesis, a state-designed curriculum that does not take into account a student’s particular strengths and interests. Essay? College is a time for students to focus on courses that are specific to their career goals.
Both online and brenner traditional classes offer education toward a degree program. Students have access to instructors in both class formats. Both involve some form of discussion among classmates. Both often have group projects. Online classes allow for more flexibility than traditional classes.
Students can take an online course at any time from the comfort of their homes. Traditional classes require students to battle essay gettysburg, attend class at a specific time and thesis location. Essay? The access to instructors is virtual in online classes and in-person in brenner thesis, traditional classes. Online classes often have discussion board posts that replace live classroom discussions. 37. Homeschooling vs. public education.
Homeschooling and public education provide specific guidelines and learning outcomes for students. Both provide a way for children to experience and learn about the how to write descriptive, world around them. Public education provides more opportunities for socialization than homeschooling. Homeschooling can be more demanding on thesis parents as they must be both full-time parent and full-time teacher. 38. Advanced placement (AP) classes vs. honors classes. Both types of classes provide more rigor than traditional high school classes and how to write an application descriptive are geared toward higher achieving students.
Both types of classes can strengthen students’ college applications. Honors courses are essentially high school courses that cover subject matter in greater depth. AP courses are designed to mirror college-level courses. High school honors courses do not allow students to earn college credit. Brenner? Some high school AP courses allow students to earn college credit. Compare and Contrast Essay Topics: Film and film resume cv Literature. Chances are, if you’ve been in English class for any length of time, you’ve been asked to compare and contrast two bodies of literature or other fictional work. This is thesis, your chance to surprise the heck out of teenage depression essay, your professor (and get a good grade) by making unexpected comparisons. Following are some topic examples. Both pieces of literature investigate vampire lore.
Both use foreshadowing as a literary device to move the story forward. Both also share three themes: attraction, addiction, and repulsion. Twilight’ s 21 st century vampires are sexy and sparkly. Brenner Thesis? Edward Cullen of Twilight is charming and over irresistibly dangerous. On the other hand, Dracula is a 19 th century blood-thirsty beast that anyone would resist. Bram Stoker’s Dracula had a thick mustache, a large nose, and white hair that “grew scantily round the temples but profusely elsewhere.” (Bella, eat your heart out.) Also, there are no werewolves in Dracula . Both Breaking Bad and Lost were hit TV series of the early 21st century. Both shows have won a Golden Globe Award and an Emmy. Thesis? Both have a character named Walt. Both use flashforward scenes to how to essay, move the narrative forward. Breaking Bad investigates the concept of the anti-hero in the character Walter White, who is easy to hate but hard not to cheer on as he descends into a life of crime.
Lost investigates the virtues of a classic hero in the likeable character of thesis, Jack Shephard. 41. A Rose for difference and personal, Emily vs. The Yellow Wallpaper. Both stories depict women being forced into isolation as a result of brenner thesis, “lunacy.” Both stories explore the definition of femininity and write an application essay the repression of women. Both stories explore dysfunctional relationships between women and men. “The Yellow Wallpaper” tells the thesis, story of how to an application descriptive, a woman’s experience of being shut into brenner a bedroom for film resume cv, a summer. “A Rose for brenner thesis, Emily” explores a woman’s experience of shutting herself into a house for 40 years. Essay Gettysburg? Both stories investigate these themes in thesis, very different ways.
42. Fahrenheit 451 vs. Essay? Red Scarf Girl. Both stories uncover themes of brenner thesis, cultural repression. Both stories revolve around the human experience of how to write an application descriptive, defying unjust government regulations. Censorship and loss of individual rights are themes in both books. Fahrenheit 451 is a science fiction novel about how the brenner thesis, character Montag defies authority and battle gettysburg begins to read the books that he had been ordered to brenner, burn. Red Scarf Girl is film resume cv, a true story about a young girl, Ji-li, and thesis her experience of film resume cv, defiance and resistance during China’s cultural revolution.
43. The Day After Tomorrow vs. I am Legend. Both movies address the theme of the apocalypse and thesis post-apocalyptic struggles for survival. Both movies touch on deeply rooted fears of humanity and our intrinsic understanding that the human race must eventually meet its end. And Personal For College? Both showcase a lone scientific hero who tries to save humanity. In I Am Legend, the harbinger of the apocalypse is a plague that turns people into killer monsters. In the Day After Tomorrow , an out-of-control storm ushers in an apocalyptic ice age. Both novels create a dystopian vision of life in the future where society has been divided into factions. Both novels are coming-of-age love stories. Both stories require the female protagonists to partake in violent rituals.
The Hunger Games explores themes of violence and corruption, and the defiance of unjust authority. Thesis? Divergent explores themes of following your heart despite the odds. 45. The Strange Case of Dr. Jekyll and Mr. Hyde vs.
The Picture of Dorian Gray. Both of these stories feature a protagonist with a dark side that they try to hide from the world. Through such a lens, both stories share the theme of duality. While Dr. Jekyll swings from being good and an application essay bad, Dorian Gray slowly transforms from good to bad as the story progresses. Dr. Jekyll outwardly manifests his dark side as Mr. Hyde, but Dorian keeps his darkness hidden, only acting on thesis his impulses in secret. Dorian’s portrait is the only outward clue of his wrongdoing—the picture reveals his true nature with every wicked act. Both novels tell the story of a dystopian future where society is essay the chosen, oppressed by thesis an all-knowing and watchful authority. Both novels also have segments of the population in extreme poverty.
1984 is commentary on the dangers of a totalitarian state, and it’s set in Europe. The protagonist is an film resume cv, adult man. The Hunger Games is a coming-of-age story with a US-inspired setting. The protagonist is a young woman. These two Shakespearean plays have a lot of common. They both revolve around regicide (the murder of a king). Both involve power plays, scandals, and manipulation (but don’t all Shakespeare tragedies?). Macbeth relies on prophecies and the fulfillment of prophecies as one of its main literary hooks—it’s a story filled with magic and witches. Julius Caesar is realism-based, focusing on the plausible dramas and tragedies of the Roman Empire. Both have cool, wolfish names.
Both are heroes who undertake epic adventures to fight evil. Both experience serious transitions during their journeys. Beowulf was created in the ancient stew of medieval literature. Wolverine was created in 1974. Beowulf revels in glories, while Wolverine’s good deeds go without reward.
Beowulf and Odysseus both must battle monsters on their epic journeys. Both heroes share many of the same traits: courage, intelligence, and strength. Both men use all three traits to win their respective battles. Odysseus makes it safely home and dies in brenner thesis, his old age. Beowulf dies after slaying a dragon. Odysseus uses deception while battling enemies, while Beowulf doesn’t play games to gain an advantage against film resume cv his enemies. 50. 12 Angry Men stage play vs. a film adaptation of 12 Angry Men. Both the play and the movie follow the same basic plot, with jurors attempting to determine the guilt of the brenner, accused. Gay Marriage Discursive? In both, the jurors are nameless, known only by their juror numbers.
The scenes are more detailed in brenner, the movie compared to the descriptions in the play. The producers took some liberties with adding and/or altering dialogue from the original screenplay. Bonus info: 12 Angry Men was made into a movie in 1957 and in 1997. You might also write a compare and and personal contrast essay about the brenner thesis, two film adaptations. Compare and Contrast Essay Topics: Art. Compare and Contrast Essay Topics: Culture and Society. Here are some ideas. 57.
Korean concept of beauty vs. American concept of beauty. Both Americans and Koreans value thinness as an ideal beauty standard. Both cultures hold ideals of teenage essay, beauty that are impossible for brenner, most people to achieve. Americans focus on beauty standards, such as blonde hair, blue eyes, big breasts (on women), round butts, and tans. Gettysburg? Korean beauty focuses on ideal face and eye shapes and thesis pale skin. Cohabitation and marriage both involve two people living together and sharing resources. Both also usually mean two people are in a serious relationship. Marriage involves a legal and binding contract between two people that includes healthcare benefits and tax benefits. Cohabitation does not require a legal contract and does not include such benefits.
Both teenagers and toddlers are moody, willful, and essay needy. Both teens and toddlers are usually exploring newly found independence. Both often require supervision in many areas. Teenagers are more mobile than toddlers and brenner can be far more destructive in their actions. Toddlers are a thousand times more adorable than teenagers. Teenagers have the ability to reason, unlike toddlers, but rarely take advantage of this ability. 60. Essay? Traditional Chinese parenting vs. Western parenting. Both Chinese and Western parents want the brenner, best for their children.
Both educate and discipline their children in ways they feel will best prepare their children for causes teenage, the future. Compared to Western parents, Chinese parents (particularly “Tiger Moms”) are very strict. They do not allow their children much free time and stress discipline and rigid schedules. 61. Brenner? Authoritative parenting vs. permissive parenting. In both parenting styles, parents attempt to film resume cv, communicate with their children. In both styles, parents are also likely to encourage creativity and expression in their children. Authoritative parents are assertive and in control while not being extremely demanding. Thesis? Permissive parents are more lenient and likely to teenage, avoid conflict with their children. Compare and Contrast Essay Topics: Technology. Hopefully, you’ve found a topic that will make writing your essay fun and easy.
If you need even more ideas, here is a web app that helps you compare just about anything. And here’s a cool website with compare and contrast topics galore. Once you’ve settled on a topic, I recommend reading these posts to get started with your essay: Psst. 98% of Kibin users report better grades! Get inspiration from over 500,000 example essays. About the Author.
Naomi Tepper is a former Kibin editor, the former content manager for the Kibin blog, and forever a word nerd.
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