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Bullying: High School and Flute Acoustics, Small Midwestern Towns Essay examples. Between A Leader Manager?. Bullying in schools has become a national dilemma. Flute. It affects students and makes many students not feel safe in joan of arc school. Bullying has both short term and long term effects on Acoustics Essay the victim as well as the is the difference a leader and a manager?, bully. Most of Acoustics, these problems will start in saint biography middle school and continue to growth throughout the high school year. Flute Essay. Many school have restricted rules against vicki ruiz bullying; however, many of Flute Acoustics Essay, these schools do not follow their own rules.
Students are bullied in all short of places such as hallways, locker room, bus and classrooms. It can be physical, verbally or cyber bullying that both have same emotional effect. “Junior high school students from small Midwestern towns, nearly 77 percent saying they had been victims of bullies at vicki ruiz school- 14 percent saying they’d experienced severer reaction of the abuse” says Kathleen Vail. In some cases, the bully may have their own personal background that make them be mean to others. Some of Flute Acoustics Essay, them want to advantages of animal testing, have a sense of Acoustics, power or control. Sometimes, bullies come from a family that do not teach them right things and saint of arc biography, respect for others. Parents are major influence in this problem.
They are responsible for Essay teaching their children correct morals and values. Other reason, children might be a victim of *what is the difference between and a, bully at home so they wants to Flute Acoustics Essay, show their power and control outside the house or in alp enzyme school. Some of the bullying is not been reported and Flute, the bullies takes advantage of that because they thinks it is Are we Really in the of a Depression alright to bully others. Acoustics Essay. Many students are afraid to report bullying incidents they observe because they might become targets themselves. Joan Of Arc. Why do students bully their classmates? I believe students bully other because they are insecure and Flute Acoustics, lack confidence. They use bully tactics to impress other students. Bullies accomplish on Really of a attention they get from their fellow classmates. Their hurtful actions make them feel powerful and popular. Bullies pick on students who they think are.
Related Documents: Bullying: High School and Small Midwestern Towns Essay examples. Acoustics Essay. Odering for Essay on Use Perspective New World a Small Town Market Essay. Flute Acoustics. The Ordering Process of Really in the Depression Epidemic? Essay, Smith Brother’s Grocery Principles of Acoustics, Management Team 2 Executive Summary This paper goes in-depth at just how complicated it is to biography, run a small business in Acoustics Essay a small town. With only 10 employees the main parts of Outsiderâ€™s New World, how the ordering process is Flute Essay divided among them on a daily, weekly, bi-weekly and monthly basis depended on Are we in the Midst Depression the supply in question. Flute Essay. The basic steps in ordering are inventory, ordering, delivery, stocking and selling. Different supplies are delivered at. Words 2583 - Pages 11.
Essay about Bully: Bullying and High School. Of Animal. Bully Prevention What can principals, teachers, fellow students, and society do to Flute Acoustics Essay, get involved in preventing bullying, or is christianity vs judaism this just a part of Acoustics Essay, growing up? Kameron Jacobsen at is the difference between manager? the age of Flute Acoustics Essay, 14, four months into his freshman year of high school, Kameron took his own life. Joan Of Arc. According to Acoustics, his parents, he had been the christianity, target of bullying both at Acoustics Essay Monroe Woodbury High School and away from school within the online sites like Facebook and MySpace. The bullying of Kameron took place over advantages of animal a period of two. Flute. Words 2762 - Pages 12. Citation: Spanish Language and Small Town Essay. In the Outsiderâ€™s Perspective, town of Columbus junction, Iowa. Flute Acoustics. It’s a small town no doubt it’s just like any other town you have your grocery store, gas station, convenience store, and even a few restaurants. When I lived in Are we Really in the Midst Depression Columbus junction it was not very diverse it at all there was a lot of Flute Acoustics, average “run of the is the difference between a leader and a, mill” workers that usually worked at Acoustics Essay Tyson food plant. Or they worked at the local schools a town where seeing a black person and even a Hispanic at alp enzyme the time was almost scary.
But a few years past and. Flute Acoustics Essay. Words 420 - Pages 2. Vicki Ruiz. Schools are meant for students to Flute Essay, learn. Schools are supposed to alp enzyme, help students learn how to Flute Essay, interact with others. Parents do not send their children off to school to be bullied and vicki ruiz, terrorized on a daily basis. The controversial “Zero Tolerance” policy should not be adapted in all schools. Although bullying should never be tolerated for Flute any reason, how can a child become expelled from advantages of animal school without even trying to figure out what the Flute Essay, underlying problem is? Studies have shown that school. Vicki Ruiz. Words 676 - Pages 3. able to walk through stores or just down town The Dalles and be able to know half the Flute Acoustics Essay, people I see. My family is really well known in The Dalles area and feels good for people to recognize you then to just constantly pass you by in a big city. Methodology Types. Smaller towns are a better environment to grow up in and be a part of.
Growing up in an area with the Flute Acoustics, same kids your whole life really make a good impact on of animal life that creates that lifelong bond with each other. Essay. I found out on Use Perspective New World that it is Acoustics Essay much easier to vicki ruiz, stay. Essay. Words 853 - Pages 4. Essay on of a Epidemic? Beliefs: Greatest Hits Albums and Small Town. Flute Acoustics Essay. school. Faith is something that are parents instilled in types us. Acoustics Essay. They make sure that everything is going to be ok for joan of arc our family and Acoustics, they strive to Are we Really in the Midst Depression, everything they can and they would not be able to do all of it without faith. Acoustics Essay. Faith also comes out for Are we in the Midst of a me in athletics. This type of Flute Essay, faith is directed towards my determination.
Being from alp enzyme our small town in Selma Indiana, we didn’t have anything to Flute Acoustics Essay, do besides be active in sports. For most of the on Use, kids the Flute Essay, only way that you were going to make your way out. Words 1468 - Pages 6. It was a small town. In the Are we Really Midst Depression Essay, day, it had many people roaming its streets, but at night, it was empty. Acoustics. A ghost town.
It was also near a forest, much larger than the christianity, town. One night, a man came back late from Essay work, his name was Darren. On Use Perspective New World. He went to his home, and Flute Acoustics Essay, was shocked, the front door was gone. Joan Of Arc. He ran in, started calling out for Essay his wife, Diana, and advantages, his daughter, Alice, he heard nothing. He ran upstairs, only to find their bedroom doors open and the windows shattered. Darren took a step back. Words 461 - Pages 2. Flute. Bullying: High School and World Wide Impact Essay. 100,000 people. Alp Enzyme. Suicide is the second leading cause of Acoustics, death for people ages 10-24, behind motor vehicle accidents.
The death of a young person is always a waste of types, life, so how many more lives must be wasted before something is done? Amanda Todd was a sixteen year old girl who was severely bullied online as well as in Flute Essay school. She posted a “Goodbye/ this is advantages testing my story” video on Youtube and then committed suicide in Flute October of 2012. Are We Really Midst. The next day, Amanda’s story was all over the news. Although her story is heart breaking, it opened people’s eyes to how fatal any form of Flute Essay, bullying can be. Vs Judaism. Her story also helped parents understand how bullying has changed and become worse since they were in high school.
Words 475 - Pages 2. ?High School Imagine this… You forget to set your alarm, so you wake up late. Flute Acoustics Essay. You rush to is the between a leader and a, get ready. As you are driving out Flute of the driveway you realize you are low on advantages gas. You finally make it to Flute, class, but you are late. Vicki Ruiz. One more tardy and you have Saturday school. Your second period class has a pop quiz which you are not prepared for.
When you go to the restroom you over hear two of Flute, your friends making fun of research methodology, your outfit. Flute Essay. You are wondering if this day could possible get any worse. And then it. Research Types. Words 547 - Pages 3. Essay Scholarship: Lost and Small Town Atmosphere. Flute Essay. Michelle Locke English 12 March 23,2015 I can’t choose just one “Armada Moment” to share with you, and if I chose to share all of them, this essay would never end. I moved to Armada when I was two, grew up here, went to school here, and had the first chapter of saint biography, my life here. Flute Acoustics Essay. Most people think living in methodology types small farming town would be extremely boring, but it isn’t. Life here is nothing like New York City, but I would choose Armada over New York anyday. If I’m going to be completely.
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Smalls-Mantey, Sample F31 Application and Summary Statement. We are truly indebted to the grantee who allowed us to post this outstanding F31 sample application to help the Flute Acoustics, next generation of investigators write applications. The F31 sample application below doesn’t reflect the between manager?, complex layouts of the actual SF 424 PDF forms. Instead, we’ve provided a list of key fields from those forms and Flute, the applicant’s responses. In addition, we redacted some applicant-specific information such as contact information, publications in 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 the PI, the alp enzyme, grantee organization, and NIAID are credited. Questions?
Contact email@example.com. Acoustics? We also offer other outstanding Sample Applications. [Our Web version of this sample application can't reproduce the alp enzyme, layout of the actual PDF forms. Here is the summary that eRA Commons generated at the start of the Flute, sample app, which reflects many key fields from that form.] Project/Performance Site Locations.
[Our Web version of this sample application can't reproduce the layout of the joan of arc, actual PDF forms. Performance sites are in New York, Maryland, and the United Kingdom.] Research Related Other Project Information. [Our Web version of this sample application can't reproduce the layout of the actual PDF forms. Here are the key fields from Acoustics Essay, that form and the applicant's responses.] Understanding the of arc biography, 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 Acoustics Essay, 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 saint joan of arc, understand the magnitude and characteristics of the best responses achieved by natural infection. First, we will compare ADCC mediated by Flute Acoustics the sera of a cohort of patients using a granzyme B cytotoxicity assay developed in alp enzyme, 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 Flute Acoustics epitope specificity, affinity, potency, breadth, IgG isotype, and Fc type.
We will also evaluate whether ADCC is is the, disparate from classical neutralization. Finally, we will use microscopy to examine the synapse between effectors, Abs, and targets. The outcome of this research will provide insight into the characteristics of Abs that mediate ADCC that are likely important goals in the design of HIV vaccines or immunotherapies. Hypothesis: Antibody-dependent cellular cytotoxicity (ADCC) is a function that has been shown to mediate protection from Flute Essay, lentiviral infection. We hypothesize that variations in ADCC activity of alp enzyme, sera are dictated by Acoustics Essay the amount, specificity, and subclass of research types, 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. 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 Acoustics, role of antibody-dependent cellular cytotoxicity (ADCC) in HIV could provide important insights for of animal induction of this activity through vaccination.
This project seeks to Flute Essay, characterize the Abs that mediate ADCC and joan, image the functional synapse formed by Flute Essay cellular components involved in ADCC with the alp enzyme, goal of defining new goals for the development of HIV vaccines and therapeutics. Gallo RC, Salahuddin SZ, Popovic M. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Flute? Science. 1984; 224: 500-3. Barre-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS).
Science. 1983; 220(4599): 868-71. Organization WH. Global summary of the AIDS epidemic, December 2007. 2007 [cited 2009 September 18, 2009]; Hessell AJ, Hangartner L, Hunter M, Havenith CE, Beurskens FJ, Bakker JM, et al. Fc receptor but not complement binding is important in antibody protection against HIV. Nature. 2007; 449(7158): 101-4. www.hivresearh.org. RV144 Phase III HIV Vaccine Trial Press Release. Alp Enzyme? 2009. Chung A, Rollman E, Johansson S, Kent SJ, Stratov I. The utility of Flute Acoustics Essay, 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. Of Arc? J Immunol. 1977; 118(3): 729-35. Forthal DN, Landucci G. In vitro reduction of virus infectivity by antibody-dependent cellmediated immunity. Journal of immunological methods. 1998; 220(1-2): 129-38.
Stratov I, Chung A, Kent SJ. Robust NK cell-mediated human immunodeficiency virus (HIV)-specific antibody-dependent responses in HIV-infected subjects. 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 the rapid fluorometric assessment of Essay, antibody-dependent cell-mediated cytotoxicity. Journal of immunological methods. 2006; 308(1-2): 53-67. Saint? Migueles SA, Osborne CM, Royce C, Compton AA, Joshi RP, Weeks KA, et al. Lytic granule loading of CD8+ T cells is Flute Acoustics Essay, 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. A Leader? Loss of Flute, 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 efferent cellular interactions in advantages testing, natural resistance directed against MHC class I deficient tumor grafts. Flute Essay? J Immunol. Essay On Use Outsiderâ€™s New World? 1988; 140(2): 671-8. Flute? De Maria A, Ferraris A, Guastella M, Pilia S, Cantoni C, Polero L, et al. Expression of HLA class I-specific inhibitory natural killer cell receptors in HIV-specific cytolytic T lymphocytes: impairment of specific cytolytic functions. Proceedings of the National Academy of Sciences of the United States of America.
1997; 94(19): 10285-8. Ahmad R, Sindhu ST, Toma E, Morisset R, Vincelette J, Menezes J, et al. Evidence for a correlation between antibody-dependent cellular cytotoxicity-mediating anti-HIV-1 antibodies and 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. Alp Enzyme? Heterogeneous neutralizing antibody and antibody-dependent cell cytotoxicity responses in HIV-1 elite controllers.
AIDS. Flute Acoustics? 2009; 23(8): 897-906. Dalgleish A, Sinclair A, Steel M, Beatson D, Ludlam C, Habeshaw J. Failure of 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. Antigenic specificity of antibody-dependent cell-mediated cytotoxicity directed against human immunodeficiency virus in antibody-positive sera. J Virol. 1989; 63(2): 584-90. Doria-Rose NA, Connors M. Of An Perspective In Brave? Antibody-secreting B cells in HIV infection. Curr Opin HIV AIDS. 2009; 4(5): 426-30.
Burke B, Barnett SW. Broadening our view of protective antibody responses against HIV. Essay? Current HIV research. 2007; 5(6): 625-41. Christianity? Sattentau Q. Avoiding the Flute Acoustics Essay, 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. Advantages Of Animal? 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 macrophages to T cells across transient virological synapses. Flute Acoustics? Blood. Essay On Use Of An Outsiderâ€™s? 2008; 111(9): 4660-3. Martin N, Welsch S, Jolly C, Briggs JA, Vaux D, Sattentau QJ. Virological synapsemediated spread of human immunodeficiency virus type 1 between T cells is Flute, sensitive to entry inhibition. J Virol. 2010; 84(7): 3516-27. Intellectual Support : My mentors Mark Connors and Quentin Sattentau are leading experts in their field and have mentored numerous people that have gone on to successful careers in science. This dual mentorship will teach me to aggressively approach science from Essay of an Perspective in Brave New World, two distinctive perspectives in my graduate career, something most PhD scientist don’t experience until their first post-doctoral experience.
While at NIH I will have received extensive support of staff from Richard Siegel, Director of the NIH MD/PhD partnership program and Michael Lenardo, Director the NIH/Oxford/Cambridge Scholars Program. While at Acoustics 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 *what between a leader and a the Centre for Flute Acoustics Excellence in Teaching and Learning for training in teaching skills.
I will also take courses pertinent to my research offered at the Dunn School of Pathology. Of Arc? Both the NIH and Oxford have libraries and IT staff that can aid me in scholarly research. Physical Resources : Both labs have sufficient funding to provided me any reagent/equipement need for the proposed research. Lab Space – I am provided with a desk and personal desktop computer. Bench space is shared within the Flute, lab. Difference A Leader And A Manager?? Safety – In order to 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 patients enrolled within our protocol. We also have access to Flute, the NIH blood blank for normal human blood samples. As provided by Quentin Sattentau: “Oxford University is held in high international regard for its strong teaching and research background and its unique and personal teaching style.
Within the University the Department of Pathology has an excellent reputation for graduate teaching, and has achieved 100% success in vs judaism, 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 possibility of a cosupervisor, a departmental advisor, and a college advisor. Flute? The supervisor(s) will generally meet with the student multiple times a term, and each of the non-supervisory mentors will meet with the candidate approximately once a term and will file reports on the candidate’s progress. Of An Outsiderâ€™s Perspective In Brave? The candidate will be expected to attend a series of high profile external seminars that take place once a week in Flute Acoustics Essay, term time, and a regular series of Perspective New World, internal seminars from leading and more junior University and Departmental investigators and students. Adjoa will attend and Flute Acoustics, participate in 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. Christianity Vs Judaism? Adjoa will also be encouraged to Flute Acoustics, chat to types, other members of the department during tea lunch and Acoustics Essay, coffee breaks, a longstanding Oxford institution! The Department has a fully equipped quiet library for literature research and other reading and research methodology, writing. Adjoa will have her own writing up space close to her work bench, equipped with a portable computer and if required, an external screen.
Adjoa will have full access to 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 chemistry departments and the Weatherall Institute of Flute, Molecular Medicine at the John Radcliffe Hospital for obtaining clinical samples and research, 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. Flute Acoustics? The laboratory has a new tissue culture facility comprised of 8 double hoods and associated incubators and ancillary equipment that is shared with three other virology groups. Virology. The department has a large, fully-equipped containment-III laboratory shared between two groups, with three tissue culture hoods and associated incubators and ancillary equipment, in which HIV-1 is grown and used to alp enzyme, infect cells. Flow cytometry. The department has a core flow cytometry facility with three BD analyzers (2 x FACScalibur 2 x LSR2) and Flute Essay, two sorters. Molecular biology. The Sattentau laboratory has all facilities for molecular biology carried out on Use of an Perspective in Brave, under containment levels –I, -II and Flute Acoustics, –III. Light microscopy.
The department has 5 confocal microscopes of varying sophistication and christianity vs judaism, 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 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 Acoustics 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 Essay on Use Perspective in Brave New World Catholic University the following summer I came to understand how medical research impacts treatment for routine illnesses and also plays a role in national defense. Since middle school I have been preparing for a career in science. At Eleanor Roosevelt High School I was enrolled in the rigorous Science and Technology Program during which time in participated in Flute Acoustics Essay, the Gene Search Project and researched biochemical pathways that influence sickle cell anemia with Dr. William Winters at Howard University Hospital. This experience taught me how research and medicine are intertwined and joan, inspired me to become a physicianscientist. At UMBC I was a member of the Essay, Meyerhoff Scholars Program and Outsiderâ€™s Perspective New World, an HHMI Undergraduate Research Scholar where numerous lab experiences, seminars, rigorous classes, and multiple opportunities for scientific presentations prepared me for 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 Essay did I learn about protein purification, gel electrophoresis, NMR, and ITC while studying MuLV RNA packaging, but more importantly of the time and alp enzyme, discipline necessary for excellent research and Flute, the internal drive that keeps one focused. Christianity? Working with Dr. Nikola Pavletich I learned the value of immediately organizing my data so that others could analyze my results quickly. In the Acoustics Essay, lab of Tom Cech I had the christianity vs judaism, responsibility of designing a new protocol to study telomerase assembly, a skill that has enabled me to Acoustics Essay, design a novel assay to investigate AIDS specific questions in my graduate studies. Of An Outsiderâ€™s? The medical education I’ve received at Flute Acoustics Essay Columbia has given me a unique perspective with which I approach scientific questions. Under the tutelage of Mark Connors and Quentin Sattentau, leaders in their fields on Essay of an New World nonprogressive HIV infection and Essay, viral transmission, my understanding of infectious disease and my capacity to pursue further research in testing, these fields will be greatly enhanced. In addition, the courses, medical preceptorships, presentations, teaching, and career development activities I am undertaking in Acoustics Essay, the forthcoming years make me an 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 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. 2005. Composition and sequence-dependent binding of RNA to the nucleocapsid protein of Moloney murine leukemia virus. Biography? 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. Acoustics Essay? 2010. Structure of a conserved retroviral RNA packaging element by NMR spectroscopy and cryo-electron tomography. J Mol Biol.
404(5), 751-772. Smalls-Mantey A, Winter W. 2003. Biosynthesis of 2,3-diphosphoglycerate in Erythrocytes. Poster presentation at ERHS Science Fair and Prince Georges County Science Fair. March 2003. Smalls-Mantey A, Dey, A, Phillip C, Summers MF.
2004. Characterization of High-Affinity Nucleocapsid Protein Binding Sites Within the Moloney Murine Leukemia Virus RNA Packaging Signal. Poster presented at 2004 Annual Biomedical Research Conference for Minority Students, November 2004. Smalls-Mantey A, Min J, Pavletich N. 2005. Structural and Biochemical Studies of the Yeast Rad4-Rad23 Complex Bound to DNA. Poster presented at Tri-Institutional Gateways to the Laboratory Program Symposium and 2005 Leadership Alliance.
August 2005. Alp Enzyme? 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. April 2007. Smalls-Mantey A, Klein R, Doria-Rose N, Laub L, Rood J, Migueles S, Sattenatu. Flute Acoustics? 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. Types? 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 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. Essay? 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 Essay on Use Outsiderâ€™s Perspective in Brave New World 2010 International AIDS Vaccine Conference. September 2010. Smalls-Mantey A. 2010. Antibody-Dependent Cellular Cytotoxicity and the Control of HIV. Talk given at Frontiers in Biomedicine NIH/Oxford/Cambridge Scholars Program student presentation series. Flute Acoustics Essay? November 2010. [Outside research support redacted from sample.] A. Personal Statement Regarding Project. Currently HIV-specific ADCC is considered one of the very top priorities in the field of christianity vs judaism, HIV-specific immunity. Flute Essay? Our laboratory has assembled the best techniques and reagents in advantages of animal, 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 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. Flute Acoustics Essay? Public Health Service, Research Associate (C.O.), Respiratory Viruses Section, Laboratory of a leader and a, Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Flute Essay, Health, Bethesda, MD July 1993 - June 1994 U.S. Public Health Service, Clinical Associate, Clinical Center, National Institute of Allergy and Infectious Diseases, National Institutes of methodology types, Health, Bethesda, MD January 1994 - June 1994 Clinical Fellow in Infectious Diseases, The Childrens Hospital of Philadelphia, Philadelphia, PA. June 1994 - December 2004 U.S.
Public Health Service, Medical Officer, National Institute of Allergy and Infectious Diseases, Clinical and Essay, Molecular Retrovirology Section, Laboratory of Immunoregulation, National Institutes of research, Health, Bethesda, MD December 2007- Present Chief, HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Essay, Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. Recent Honors and Editorial and of animal, Review Board Activities. 2009 - U.S. Public Health Service Outstanding Service Medal 2009 - present Vaccine Production Development Team Scientific Advisory Board, University of Pennsylvania 2009 - present HIV Enterprise Host Genetics and HIV Diversity Working Group 2010 - present Editorial Board, Journal of Acoustics, 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 a subgroup of HIV infected long term nonprogressors. PNAS 2000; 97(6): 2709-2714. Vs Judaism? 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. Flute? Nature Immunol 2002; 3(11); 1061-1068. Migueles SA, Laborico AC, Imamichi H, Shupert WL, Royce C, McLaughlin M, Ehler L, Metcalf J, Liu S, Hallahan CW, and Connors M. The differential ability of christianity, HLA B*5701+ long-term nonprogressors and progressors to restrict HIV replication is not caused by loss of recognition of autologous viral gag sequences.
J Virol 2003; 77(12); 6889-6898. Iyasere C, Tilton JC, Johnson AJ, Younes S, Yassine-Diab B, Sekaly RP, Kwok WW, Migueles SA, Laborico AC, Shupert WL, Hallahan CW, Davey RT Jr., Dybul M, Vogel S, Metcalf J, and Connors M. Flute Essay? Diminished proliferation of saint of arc, HIV-specific CD4+ T Cells is associated with diminished IL-2 production and recovered by exogenous IL-2. J Virol 2003; 77(20); 10900-10909. Tilton JC, Luskin MR, Johnson AJ, Manion M, Hallahan CW, Metcalf JA, McLaughlin M, Davey RT Jr., and Connors M. Changes in paracrine IL-2 requirement, CCR7 expression, frequency, and cytokine secretion, of HIV-specific CD4+ T cells are a consequence of antigen load. J Virol 2007; 81;2713-2725. Migueles SA, Osborne CM, Royce C, Compton AA, Joshi RP, Weeks KA, Rood JE, Berkley AM, Sacha JB, Cogliano-Shutta NA, Lloyd M, Roby G, Kwan R, McLaughlin M, Stallings S, Rehm C, O’Shea MA, Mican J, Packard B, Komoriya A, Palmer S, Wiegand AP, Maldarelli F, Coffin JM, Mellors JW, Hallahan CW, Follman DA and Flute Acoustics, Connors M. Lytic Granule Loading of CD8+ T-Cells is alp enzyme, 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 Flute, 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 advantages, association with clinical variables. J Virol 2009 84(3): 1631-1636.
Doria-Rose NA and Connors M. Antibody-secreting B cells in HIV infection. Curr Opin HIV AIDS 2009 4:426-430 Wu X, Yang ZY, Li Y, Hogerkorp CM, Schief WR, Seaman MS, Zhou T, Schmidt SD, Wu L, Xu L, Longo NS, McKee K, O'Dell S, Louder MK, Wycuff DL, Feng Y, Nason M, Doria-Rose N, Connors M, Kwong PD, Roederer M, Wyatt RT, Nabel GJ and Mascola JR. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 2010 329:856-861. Migueles SA and Flute, Connors M. Long-term nonprogressive disease among untreated HIV-infected individuals: clinical implications of understanding immune control of HIV. Christianity? JAMA 2010 304:194-201. [Redacted publication in press]
The research direction of the HIV-Specific Immunity Section of the Laboratory of Immunoregulation is focused upon mechanisms of immunity to HIV. The laboratory is staffed by PhD and MD scientists with extensive experience in the humoral or cellular immune response to HIV. In addition we have close collaborations with investigators at the NIAID Vaccine Research Center in the area of structure-function relationships of HIV-specific antibodies. Our laboratory is Flute Essay, well equipped with multi-laser flow cytometers, automated magnetic sorters, and imaging equipment to carry out this project. Our laboratory is supported by the research budget of the Division of Intramural Research. Over the past 4 years we have received supplemental funding from the Intramural AIDS Targeted Antiretroviral Program (IATAP).
This will continue for the next 2 years. We have also received funding from the methodology, Office of AIDS Research for Essay work on the humoral response to HIV. Positions and Employment. 1985 - 1992 Lecturer, Department of Genito-Urinary Medicine, University College London, UK 1989 - 1991 Visiting scientist, Howard Hughes Medical Institute, Columbia University, New York, NY 1992 - 1998 Staff scientist (Director of Research), Centre d’Immunologie, Marseille, France 1999 - 2003 Reader, Section of Infectious Disease, Imperial College London, London UK 2003 - Professor of advantages testing, 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 Immunology, UK 1998 - Member, Society for General Microbiology, UK 2005 - Member of the Pasteur Institute Paris France Scientific Evaluation Committee. 2005 - Member of the Vaccine Research Center (VRC) NIH Board of Flute Essay, Scientific Councilors 2007 - Member of BMGF Vaccine Monitoring Centre SAB 2008 - Member of NIH HIVRAD/Novartis Neutralizing Antibody Vaccine Consortium SAB 2009 - Member of study section for Swedish Program for International Development 2010 - Member of NIH study section for the B cell Immunology Partnership Program for HIV-1 Vaccine Discovery (U19) C. Essay Of An Perspective New World? Selected Peer-Reviewed Publications. Most relevant to the current application. Martin N, Welsch S, Jolly C, Briggs JA, Vaux D and Acoustics, Sattentau QJ. Essay On Use In Brave New World? (2010) Virological synapse-mediated spread of Essay, 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 of an Outsiderâ€™s in Brave New World, Alcami J. (2010) SDF-1/CXCL12 production by mature dendritic cells inhibits the propagation of X4-tropic HIV-1 isolates at the dendritic cell-T-cell infectious synapse. Essay? J Virol. 84:4341-51 Groot F, Welsch S and 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 Davis DM (2008). Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission. Nature Cell. Testing? Biol. 10: 211-219. Jolly C and Sattentau QJ (2007).
HIV-1 assembly, budding and cell-cell spread in T cells takes place in Essay, tetraspanin-enriched plasma membrane. J. Virol. 81:7873-7884 Jolly C and Sattentau QJ (2007). Saint Biography? 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). Acoustics? Requirement for an intact actin and tubulin cytoskeleton for saint efficient HIV-1 assembly and spread. J. Virol. Acoustics Essay? 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. 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. Saint Of Arc Biography? J. Mol. Biol. Aug 25th epub. Krashias G, Simon K, Wegmann F, Kok WL, Ho LP, Stevens D, Skehel J, Heeney JL, Moghaddam AE and Sattentau QJ. (2010). Potent adaptive immune responses induced against 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. SIV spike glycoprotein structure in Acoustics Essay, situ determined by cryo-electron tomography. Plos Pathogens August 2 (8): e83 Sheppard NC, Bates AC and *what is the difference and a, Sattentau QJ (2007). A functional human IgM response to HIV-1 Env after immunization with NYVAC-HIV C. Acoustics? AIDS 19: 524-527. [Outside research support redacted from sample.] PHS Fellowship Supplemental Form, Research Plan.
[Our Web version of joan, this sample application can't reproduce the layout of the actual PDF forms. Essay? 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 alp enzyme 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 Acoustics Essay, most recent vaccine trials. Is The Difference Between And A? 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 Flute Essay, Ab and use perforin to deliver granzymes which induce apoptosis in the target. We want to study ADCC in of arc, infected patients to understand the Flute Acoustics, 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 saint 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. Finally we will use microscopy to examine the synapse between effectors, Abs, and targets. The outcome of this research will provide insight into the characteristics of Abs that mediate ADCC that are likely important goals in the design of HIV vaccines or immunotherapies.
Hypothesis: Antibody-dependent cellular cytotoxicity (ADCC) is a function that has been shown to Acoustics, mediate protection from lentiviral infection. We hypothesize that variations in ADCC activity of sera are dictated by research methodology 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 infected CD4+ T cells. NKs expressing an Fc receptor bind the Fc domain of the Ab and use perforin to Flute Essay, deliver granzymes to the HIV-infected cell. Saint? Subsequently, granzymes induce apoptosis within the cell. Our lab has developed a flow cytometric assay that measures granzyme B delivered to Flute Essay, an HIV-infected CD4+ target T cell. We will classify ADCC by research methodology types 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 Flute Essay, mediating the highest levels of ADCC.
Compare the ADCC and types, neutralizing activity of patient sera. Aim 2 : Characterize the specificity and breadth of antibodies with ADCC activity. Our laboratory has panels of NAbs derived from patients with known serum neutralizing or ADCC-mediating activity. Determine whether recognition of specific epitopes is required for ADCC. Acoustics? Define the breadth of the advantages of animal, polyclonal sera by its ability to Acoustics, mediate ADCC in CD4+ T cells infected by different clades of HIV. Is The Difference Between And A Manager?? Titer serum total IgG, IgG1, and Essay, IgG3 binding infected CD4+ T cells. Aim 3 : Characterize the Essay of an Outsiderâ€™s New World, 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, we will examine the synapse formed between NK and other cells with potential ADCC activity (macrophages and neutrophils) and infected target cells. We will specifically investigate: The structure of a functional ADCC synapse. The kinetics of ADCC function in Acoustics, real time and its relation to antibody type and specificity. A role for antibody-dependent cell-mediated phagocytosis (ADCP) in elimination of HIV-infected cells. d. Receptors and methodology, effector molecules central to Flute Acoustics Essay, ADCC activity against HIV infected cells. Since being identified as the causative agent of AIDS in 1983, HIV infection has reached epidemic proportions with an estimated 2 million people worldwide dying from AIDS each year 1- 3. There is more public awareness about how to prevent HIV infection but with the Outsiderâ€™s in Brave, 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 Acoustics Essay HIV is the search for correlates of *what is the and a, immunity. At present the only method for determining the potential benefits of a vaccine with regard to Flute Acoustics, protection from infection or lowering of viral load upon infection remains very large clinical efficacy trials.
Determining correlates of testing, immunity would tremendously accelerate the Essay, development process by Essay on Use of an Perspective permitting some estimation of clinical efficacy prior to 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 HIV have largely focused on CD8+ cytotoxic T lymphocytes (CTLs) or neutralizing antibodies (NAbs). In addition to Essay, 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 infected target cells and Fc? receptor-bearing effector cells such as natural killer cells (NKs) recognize and bind the 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 research methodology types, 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 Acoustics, 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. Prior to joan, this study, it was widely accepted that infection of a single cell would lead to Flute, 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 vivo. *what Difference Between A Leader And A? 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 HIV.
In September 2009 data from the Flute Essay, 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 Perspective, protective efficacy is likely mediated through ADCC 5. Our laboratory is part of a large international effort to characterize ADCC antibodies from this trial in Flute, order to determine whether there were higher ADCC-mediating antibodies in uninfected vaccinees compared to those that were infected. Although HIV-specific ADCC is now considered an extremely important part of vs judaism, vaccineinduced immunity several basic questions regarding the nature of an effective ADCC response have not been addressed. Acoustics? For example, the advantages of animal, number, affinity, and Essay, specificities of 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 *what is the difference between and a, initial goals of this project was to adapt our current killing assay to provide a more robust assay for Acoustics HIV-specific ADCC. Past studies of ADCC have been hampered by the availability of assays that are only partially quantitative. There are four primary methods that people use to measure ADCC 6. The most prevalent is the chromium release assays (CRA), which is saint joan of arc, 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 Flute Acoustics Essay, the B95-8 cell line for christianity 5-7 days. Acoustics Essay? The endpoint is reduction of viral infection of the B95-8 cells 8. This method measures inhibition of Essay of an in Brave, viral production and subsequent infection but its disadvantages lie in the length of the assay and failure to Acoustics Essay, measure killing of infected cells.
Another assay is the intracellular cytokine staining ADCC (ICS-ADCC) assay measures IFN-?, the Essay on Use Perspective in Brave New World, 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 Flute Acoustics Essay, 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. Advantages? While use of protein pulsed targets is a sensitive method, it likely places artificially high amounts of protein on the surface of Flute Essay, 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. Alp Enzyme? This is an adaptation of an assay for measuring the cytotoxic activity of CTLs developed in our lab11. Flute Essay? This assay measures the cleavage of a GrB substrate, and vs judaism, 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. Flute Acoustics Essay? 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. Alp Enzyme? Granzyme delivery to the target cell and elimination of HIV-infected targets can then be measured by flow cytometry (Figure 1). Cellular GrB content. GrB cleaves GranToxiLux substrate (FITC), indicating the Flute Essay, amount of GrB present within a target cell (Pacific Blue). Alp Enzyme? Elimination of HIVSF162-infected cells. Live targets are stained for intracellular HIV capsid, p24 (PE). Some infected cells show downregulation of CD4 (PE-Cy7). A reduction in the number of Acoustics, p24 stained cells is alp enzyme, represented as Infected Cell Elimination (ICE) and is an Flute indication of cell death. In the christianity, example above, ICEInfected+Effectors+Serum = [(58.2-25.8)/58.2] x 100 = 54.9%. There are several advantages to Flute, 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. Of Arc? 12. In addition, because NK function is diminished in HIV-infected patients, we use the Flute Acoustics, 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 saint joan of arc biography, NKs from normal individuals in Acoustics, their ability to mediate ADCC and choose donors that provide optimal signal to saint of arc, noise ratio that we will use to compare the serum of HIV+ individuals (Figure 2). The targets used in this assay are likely closer to 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 Flute Essay, ADCC (granzyme delivery) and the outcome (death of infected cells) (Figure 2). Alp Enzyme? 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 Flute Acoustics, all CD3-bearing targets (Figure 3). 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 christianity vs judaism, a dose dependent manner, and (3) GrB delivery is Flute, proportional to *what difference and a manager?, cell death. Aim 1: Characterize the Essay, magnitude of christianity vs judaism, ADCC in HIV infected individuals . Rational : There is Flute Essay, considerable controversy regarding the magnitude of ADCC activity in sera from HIV+ individuals and how it correlates with disease progression.
It has been suggested that sera from elite controllers exhibit greater ADCC activity which correlates with CD4+ T cell count 17, 18 while others have sighted no correlation between ADCC and disease progression 19, 20.We will compare the serum of in Brave, HIV+ individuals with various rates of progression and viral loads to determine which contain Abs capable of 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 Essay, neutralization always occur together in polyclonal sera which is yet to be determined 21, 22. Methods : Over the alp enzyme, past several years, in Essay, collaboration with the Vaccine Research Center (VRC) our laboratory has focused upon *what and a manager?, recruiting HIV-infected patients with broadly crossneutralizing antibodies. We have extensive clinical data and neutralization data for Acoustics Essay all of the patients. With the *what is the difference between manager?, data we generate from Flute Acoustics, our ADCC assay we are able to Outsiderâ€™s in Brave New World, compare multiple indicators of immunity with ADCC. Expected Outcomes/Interpretation : Based on in vitro and Essay, passive transfer macaque studies, we expect LTNPs to exhibit greater ADCC than progressors. Our current knowledge attributes LTNP delayed progression to superior CTL cytotoxicity but our data may show ADCC also to be a significant factor 11. Potential Complications : We do not foresee any difficulties in accomplishing this objective.
Aim 2: Characterize MAb from vs judaism, serum identified as having potent ADCC activity with regard to Flute Essay, specificity. Rational/Methods : HIV-infected cells express Envelope (Env) protein on their surface which is christianity, recognized by NAbs and presumably by ADCC-mediating Abs. Flute Essay? We will use standard Nabs (including b12, 2F5, 2G12, 447-52D, 17B, and VRC01) and patient derived MAbs to probe specificities required for ADCC. Joan? An ideal HIV vaccine would be able to Flute Essay, protect against diverse virus strains so it is important to saint joan biography, determine whether Abs raised against one clade of Flute, virus would be able to mediate ADCC in CD4+ T cells infected by different clades. *what Between And A? 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 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 Flute Essay, ADCC activity of sera are mediated by variations in IgG subclass. We will use infected CD4+ T cells, apply sera with various levels ADCC at the same dilutions used in our killing assay, and measure total bound IgG, IgG1, and IgG3 by flow cytometry.
We believe flow cytometry is a better way of is the between a leader and a, measuring titers of binding Abs as compared to ELISA because Abs will recognize all possible epitopes on the surface of an infected cell in their natural conformation. Expected Outcomes/Interpretation : Determining the association between ADCC activity and IgG subclass may provide insights into the necessity of eliciting a specific class of IgG via particular antigens and adjuvants. Potential Complications : We now have robust assays for subclass binding and Flute Essay, do not expect complications with this portion of the project. Aim 3: Evaluation of the target-effector synapse. Rational : Using microscopy to study ADCC is important because it will help us define structural and kinetic parameters and advantages of animal testing, will relate structure to function.
Multiple mechanisms for Flute Acoustics cell-to-cell spread of 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 HIV using NKs or macrophages as effectors and CD4+ T cells as targets. In 1994 one group designed a bispecific antibody with anti-CD4 and anti CD3 heavy chains that would redirect CD8+ T cells to types, kill HIV infected targets 24. 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. At 2 hours 50 - 80% of Flute Acoustics Essay, targets were conjugated and *what is the difference between a leader, undergoing lysis and by 24 hours all targets had been lysed. However, the bispecific antibody may not be representative of ADCC with naturally occurring HIV-specific antibodies. In addition, the structure of the Acoustics, NK to HIV-infected target synapse was not examined. Methods : The lab of Quentin Sattentau has focused on Essay Outsiderâ€™s in Brave examining the synapse of cells involved in HIV infection.
They were the first to demonstrate HIV-1 spread between T cells via virological synapses and nanotube structures for Acoustics Essay viral transmission between CD4+ T cells 25. They have recently demonstrated that macrophages can infect CD4+ T cells every 6 hours and alp enzyme, that cell-tocell transfer of virus is 10-fold more efficient than free virus spread 26. To study the kinetics of ADCC in real time we will use time-lapse laser scanning confocal microscopy (time-lapse LSCM). Flute Acoustics? Cell populations will be negatively selected from *what is the and a manager?, PBMCs using magnetic cell sorting. HIV-infected CD4+ T cells will be mixed with patient serum or Abs of multiple specificities (see Aim 2) and NKs to evaluate ADCC; or neutrophils/monocytes to evaluate antibody-dependent cell-mediated phagocytosis (ADCP) and applied to poly-L-lysine coated cover slips. Cover slips will be fixed in paraformaldehyde, quenched with NH4Cl, permeabilized with Triton-X, and stained for granzyme B, IgG, CD4/CD16/CD14 with fluorescent probes. After mounting, images will be acquired every minute for 6 hours using a Zeiss Pascal Axivert 200M scope. We will use transmission electron microscopy and tomography (TEM) to generate higher resolution static images of the Acoustics, ADCC functional synapse. For TEM targets, serum, and effectors will be incubated for approximately 1 hour, fixed in paraformaldehyde and glutaraldehyde, and stained with osmium tetroxide. Research Types? Samples will be embedded in Flute Essay, epoxy resin, cut, and christianity, imaged using a 300kV FEI Technai TF30 27.
If necessary cryo-EM will also be used for structural studies with the aid of Flute, Oxford collaborator Kay Grunewald. These experiments will be completed using the pathology department’s core bioimaging facility and I will take department’s Advanced Light Microscopy and Electron Microscopy course in preparation for this research. Expected Outcomes : We expect to saint of arc, elucidate the kinetic and functional relationship between ADCC components and answer questions such as what density of Env epitopes are needed to Flute Acoustics Essay, recruit effectors, how many effectors are recruited per target. We do not foresee any difficulties in alp enzyme, accomplishing this objective. The results of Essay, these studies will include novel MAb with possible therapeutic value; a new tool for the study of methodology types, ADCC with potential utility for HIV vaccine trials; and increased understanding of basic HIV immunology. Essay? 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 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 human subjects are in accordance with NIAID Division of Intramural Research policies.
Phlebotomy may cause some discomfort, and occasionally some bleeding or bruising at alp enzyme 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 Flute Acoustics, course of saint of arc biography, any time frame during this study, the Flute Essay, total amount of blood will not exceed 10.5mL/kg, or 550 milliliters over any 8-week period, which is within the safety guidelines for blood drawing practiced at joan of arc the Clinical Center. Like standard phlebotomy, leukapheresis is occasionally associated with local bleeding and bruising at the site of needle insertion.
Lightheadedness can also occur, and people faint on rare occasions. Occasional tingling in the arms and legs can occur with the procedure and Acoustics, can usually be relieved by chewing a calcium-rich tablet that the staff will provide. Essay Of An Outsiderâ€™s? In addition, on Flute Essay very rare occasions (less than 1 in every 1,000 times), malfunction of the leukapheresis machine can result in is the between a leader, blood loss of up to 450 milliliters. Trained medical personnel who are equipped to deal with any of Flute Acoustics, these potential problems will always be on hand during the procedure. Inclusion of Women and Minorities. Gender, Ethnicity and Race Consideration. This study involves techniques and procedures that are currently approved for various indications. Male and female adult patients (18 years of age or older) will be enrolled without preference to gender, race or ethnicity from the pool of patients that receive care in Clinics 8 at the NIH Clinical Center. Patients will be recruited from outside the NIH community by advertisements posted in the Clinical Center, the research methodology types, NIAID web site, and advertised in other media. We will attempt to facilitate minority recruitment using existing NIAID community outreach efforts involving local clinics in the Washington, DC metropolitan area.
In adult HIV-infected patients planning to interrupt HAART, patients will be fully counseled prior to 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 Acoustics, a documented virologic and/or immunologic response. Patients who do not fully comprehend these potential risks of HAART cessation, in the opinion of the Essay on Use Outsiderâ€™s New World, study team, will not be offered participation in the study. Patients stopping HAART therapy will be monitored closely for virologic and Flute Acoustics Essay, immunologic relapse and alp enzyme, will be offered therapy, based upon the algorithm for safety outlined above. Target enrollment for this study is Essay, 300 individuals and methodology types, is currently ongoing. Inclusion of Children (and Pregnant Women) Inclusion of 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 Flute Essay, this trial, thereby children are not being denied the methodology, potential benefits of a research intervention. Acoustics Essay? We also do not have the historical research database and in vitro findings on alp enzyme 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 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. Therefore, pregnant or nursing women will be excluded from Flute Acoustics Essay, 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 types 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 their focus on Acoustics HIV immunology, vaccine design, and their expertise in basic immunology techniques, flow cytometry, and microscopy. Essay Perspective? I initiated contact between the two individuals and they agreed to Flute Essay, start a collaborative project with me. After studying NAbs with Mark Connors for difference a leader and a one summer I decided I wanted to Flute Acoustics Essay, focus on antibodies that mediate ADCC. Saint Joan Of Arc? I outlined the facets of ADCC I wanted to investigate then received feedback from both mentors. I subsequently wrote the proposal that was edited by Flute Acoustics 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. Christianity? We also conduct quarterly phone conferences with Dr. Sattentau, maintain a regular email correspondence, and meet at conferences. Communication will continue in Flute, 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 vs judaism, exemplary medical education, medical research, and Flute Essay, unparalleled support offered to students from research methodology, 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 Acoustics Essay, NIH/Oxford/ Cambridge Scholars Program to complete my dissertation research because it would provide me access to a more extensive network of scientists than Columbia could. Oxford has a particularly strong network of HIV investigators and advantages of animal testing, 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 Flute Essay, attain skills quickly and immediately implement them into alp enzyme, my research. In addition, the NIH/Oxford/Cambridge Scholars program provides funding for students to take courses offered by any institution giving me access to virtually any educational opportunity necessary. In addition, through NIH’s Foundation for Advanced Education in the Sciences I’ve had the opportunity to take courses that will help me towards my goal as in infectious disease investigator such as the Vaccine Development course I completed. The NIH/Oxford/Cambridge Scholars Program is Acoustics Essay, designed so that students work with a mentor at NIH and one at saint of arc a university. Acoustics? When I joined the program I searched for HIV investigators throughout NIH and Oxford and identified Mark Connors and advantages, Quentin Sattentau as potential mentors because I wanted to conduct research that had direct implications in vaccine development.
Quentin Sattentau was studying how to Acoustics, elicit effective anti-HIV neutralizing Abs (NAbs) for vaccines and adjuvants to stimulate systemic and mucosal immunity. Through my search at the NIH I identified Mark Connors as a potential collaborator though he and Quentin had never collaborated before. I believed Dr. Connors’s expertise in of animal, NAbs of long-term nonprogressors (LTNPs) would complement Dr. Sattentau’s vaccine development goals. In addition, Dr. Acoustics Essay? Connors’s unique cohort of LTNPs would provide ready access to samples to study many facets of HIV infection. Advantages Of Animal Testing? Finally, I believe Dr. Sattentau’s approach to Acoustics Essay, research as a PhD and Dr.
Connors’ as an methodology MD will teach me to think about science in a more practical way that is suited to me as a future MD/PhD researcher. I will follow the principles on responsible conduct of research as outlined in NOT-OD-10- 019. Flute? As an on Use of an in Brave New World undergraduate at Essay UMBC I took a semester-long course entitled “Ethics/Integrity in Scientific Research” which first help me to alp enzyme, understand the responsibility scientists have to one another and Flute Acoustics Essay, medical community honestly share information. Biography? As a Columbia medical student, I have taken the Hippocratic Oath to guide my patient care and I am expected to adhere to the code of ethics as outlined in student handbook. Upon joining the NIH I took an online ethics course and will continue to take refresher courses annually. At Oxford I will continue my ethics training by taking the required “Ethics: Introduction to Flute Acoustics Essay, 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 Essay of an Perspective in Brave NIH I participated in Acoustics, a patient confidentiality seminar. Of Animal Testing? Oxford offers an “Ethics: Confidentiality” course in Flute Essay, which I will enroll to advantages, better my further my understanding and ability to maintain ethical practices with regards to research. As a physician, I hope to alleviate an individual’s immediate suffering; and Acoustics Essay, as a scientist I hope to contribute to long-term solutions that can prevent suffering. To work most effectively at the interface of medicine and science, I have endeavored to 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 saint of arc telomerase, an enzyme that maintains healthy chromosome length. Flute? When telomerase is upregulated, as it is in 90% of advantages, carcinomas, cells can propagate indefinitely. Flute? When telomerase levels are halved, a bone-marrow failure disease called Dyskeratosis Congenita (DC) results. While looking at yeast cells with low levels of telomerase and measuring their growth rates, I noticed two things. The first was that cells with low levels of alp enzyme, telomerase grew slowly. Secondly, these cells had abnormal morphologies, as do tumor cells. These observations led me to Flute Acoustics, wonder whether the progression of methodology types, cancer in Flute, individuals with DC was slower than in *what difference a leader and a manager?, 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 Flute Acoustics, importance of keeping a broader medical picture in mind became clear to me. My goals as a physician scientist are to treat patients and conduct research that will allow me to impact patients I will never meet through therapeutic discovery; specifically serving as a creative link between science and medicine in the field of infectious disease. The training I will receive in Essay on Use of an Perspective in Brave New World, Oxford’s doctorate program will prepare me to Flute, be a competitive investigator through a tailored curriculum, expert dual-mentoring, learning to vs judaism, work in a collaborative environment, and by giving me extensive writing experience via paper submissions and even through this grant. Flute Acoustics? These are all specific skills that would be harder and take longer for me to garner through a traditional medical student experience. The advantage I have in understanding that I want to be a physician-scientist has given me the on Use of an Outsiderâ€™s Perspective in Brave, opportunity to Acoustics, carefully cultivate these skills early in my career. Activities Planned Under This Award.
Research 80%, Seminars/Courses 10%, Presentation/Career Development/Clinical 10% Research Skills : While working in Mark Connors’s lab I have acquired specific skills such to creatively study immunology such as learning to use flow cytometry. I discuss my research progress frequently during the week with Dr. Connors. We also have phone conferences and meet with Dr.
Sattentau at numerous conferences throughout the year. Writing Skills : When I entered the of animal testing, program I took a grant-writing workshop sponsored by Essay the NIH Graduate Partnership Program. I also completed a 3-day grant-writing course during my senior year of college. I will improve my writing skills through preparation of manuscripts based on my research to be submitted for publication, applying for training grants, and submission of joan biography, a report for Acoustics Essay my transfer viva (qualifying exam). I will also complete the alp enzyme, Scientific Writing from Flute, a Reader’s Perspective seminar. Discipline specific learning : I completed the advantages testing, 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 bedside clinical training : I will attend the Clinical Research Training Program (CRTP) weekly rounds. Acoustics Essay? I will also have the opportunity to be mentored by an infectious disease clinician. Presentations : I will continue to annually attend and present at pertinent Keystone Symposia and saint biography, the Annual AIDS Vaccine conference. Flute? I have also had opportunities to present posters at the NIH/Oxford Cambridge Scholars Program Colloquium and of animal testing, the Oxford Pathology Graduate Student Symposium. I have given a talk to my graduate program journal club and will have more opportunities to present my research in lab meetings. Career Development : The NIH/Oxford/Cambridge Scholars programs hosts a seminar series where leaders in government/academic research, the pharmaceutical industry, and finance speak with us about their career. Flute Essay? I also attended NIAID Fellows retreat that focused on career development.
Teaching : As I prepare to research methodology, 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 Flute Acoustics, apply microscopic imaging to studying HIV infection. I will have weekly meetings to discuss my research progress. We will have phone conferences and saint joan, meet with Dr. Acoustics? Connors at various conferences throughout the year. I have also been assigned a graduate advisor within the pathology department but not in my specific lab who will help me to objectively evaluate my research. Writing Skills : I will improve my writing skills through preparation of manuscripts based on my research to be submitted for publication and writing reviews. Research Methodology? I will complete the following 1-day courses offered at Flute Acoustics Oxford: Writing Skills – Paper and Thesis; Doctoral Thesis Writing,
Discipline specific learning : I will participate in courses and Skills Workshops offered by Oxford including “Advanced Light Microscopy,” “Electron Microscopy,” and “Introduction to Statistics.” Bench to bedside clinical training : I will attend the Nuffield Department of Clinical Medicine Grand Rounds and shadow an infectious disease clinician. Career Development : See above. I will also attend the 4-day Oxford GRADschool, a personal development course. Teaching : I will seek to be an undergraduate lab instructor and take the Oxford course “Teaching and Learning Skills” to prepare myself.
Year 3 and Year 4: Medical School (Columbia) In the christianity vs judaism, summer after 11th grade I participated in Flute Essay, the intensive 6-week Gene Search Program at the Catholic University of America that introduced me to molecular biology and research types, 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. Because of my accomplishments that summer, I was invited to participate in Acoustics Essay, an extension of the Gene Search Program during my 12th grade year. Christianity? This program inspired me to pursue a career in biomedical research because I began to understand how the Flute Acoustics Essay, principles I was learning in saint of arc, school fostered scientific discovery. As a high school senior, I worked with Dr. William Winter at Howard University School of Medicine to investigate pathways that regulate 2,3-diphosphoglycerate (2,3-DPG) levels in red blood cells (RBC). Flute? 2,3-DPG lowers the affinity of Essay on Use Perspective in Brave New World, hemoglobin for oxygen, thereby facilitating oxygen release to tissues. Patients suffering with sickle cell anemia have high levels of Flute Essay, 2,3- DPG.
While this effect may seem advantageous to patients with sickle cell anemia, deoxygenating hemoglobin ultimately causes red blood cells to *what is the difference and a, sickle by promoting hemoglobin polymerization. Previous studies indicated that adenosine might regulate 2,3-DPG levels through an interaction with the A3 receptor. To test this idea, we indirectly measured 2,3-DPG levels by using spectrophotometry to measure a by-product of the 2,3-DPG pathway. An exciting therapeutic prospect of Flute Essay, our research is that an antagonist of the A3 receptor may prevent the accumulation of and a manager?, 2,3-DPG and Flute, RBC sickling in patients with sickle cell anemia. I documented this work in a five-chapter thesis, in accordance with my high school’s Science and Technology Program, and presented it at my school’s science fair, where I was awarded third place in biochemistry. During college I spent four years working with Dr. Michael Summers to investigate Moloney Murine Leukemia Virus (MuLV) dimerization. Understanding dimerization is between a leader and a, key to developing gene and antiviral therapies.
MuLV is similar to HIV in that it is a retrovirus that packages two copies of its RNA genome. Packaging of dimerized RNA is mediated by interactions between the nucleocapsid (NC) domain of the assembling Gag polyproteins and a specific domain of the RNA called the Psi-site. Previous work in the Summers lab suggested a riboswitch mechanism for MLV genome packaging, where, in monomeric RNA, Psi-site UCUG segments capable of binding NC are sequestered by Flute Essay base pairing, but upon of animal testing, dimerization, become exposed to bind NC. My project was to investigate whether similar sequences in Essay, 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 of an Outsiderâ€™s Perspective New World an unpaired guanosine, 2) binding is enhanced in short RNAs containing terminal phosphates, and Essay, 3) binding affinity varies by more than one order of magnitude depending on alp enzyme which three nucleotides lie upstream of the guanosine. The paper I co-authored (Dey, A., et. Flute Acoustics Essay? al., 2005) extends an established model for genome recognition, in which the *what difference between a leader and a manager?, 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 Flute Acoustics Essay, the dimeric RNA. I presented this research at the 2004 ABRCMS and at multiple UMBC symposiums. I continued to investigate potential dimerization and NC-binding regions of the Psi-site using native and mutant MuLV RNA segments in gel-shift assays.
As expected from our riboswitch hypothesis, we observed NC binding preferentially to RNA dimers which was also confirmed by equilibrium dialysis. Most recently our lab published the NMR structure of 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 advantages, crystal structure of the Saccharomyces cerevisiae Rad4-Rad23 complex bound to a DNA substrate. Rad4-Rad23 is a homolog of human XPC-HR23B, a DNA damage-repair protein. In its mutated form, XPC-HR23B causes the disease Xeroderma Pigmentosum. Patients are extremely sensitive to UV-light and Flute Acoustics Essay, 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 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. Of Animal Testing? The central role telomerase plays in protecting chromosome integrity places telomerase at the heart of two common human ailments—cancer and aging. To study how and where in the cell telomerase is assembled from its RNA and protein components, we used the 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 TLC1 is exported to the cytoplasm where it associates with Sm proteins.
Mtr10p then plays a role in importing the TLC1-Sm complex back into the nucleus, where the Acoustics, telomerase holoenzyme is advantages of animal, assembled. Using cellular fractionation and real-time RT-PCR, we attempted to Essay, localize TLC1 in its various stages. During the summer between my first and second year of medical school I joined the lab of is the between a leader and a, Mark Connors where I screened patient sera for breadth and Flute Acoustics Essay, potency of 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). Is The Between A Leader Manager?? Studying NAbs peaked my interested in other anti-viral mechanisms mediated Abs and lead to my proposed project of Flute Acoustics Essay, investigating antibody-dependent cellular cytotoxicity. Each research experience has shown me the *what is the between a leader manager?, many nuances of a research career. I learned about: 1) the Acoustics, importance of basic research in alp enzyme, developing medicines, 2) the time, organization, and ingenuity it takes to conduct research, and Essay, 3) the vital role that a physician-scientist plays in translating basic research into medical treatment. Although I’ve experienced frustrations and advantages, 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 improve health care through innovative research. [Redacted from sample.] QUENTIN SATTENTAU MENTOR STATEMENT. [Redacted from sample.] [Our Web version of this sample application can't reproduce the Flute Essay, layout of the actual summary statement. See below for the data fields and critiques.] Center for Scientific Review Special Emphasis Panel.
Fellowships: AIDS Predoctoral and Postdoctoral. RESUME AND SUMMARY OF DISCUSSION: In this application, the fellowship candidate proposes to investigate antibody-dependent cellular cytotoxicity (ADCC) in HIV-infected patients do determine the extent of of an Outsiderâ€™s in Brave, protection that ADCC provides. The reviewers noted that the candidate is Flute, outstanding, with a strong record of research training and accomplishment. The candidate appears to be highly motivated. Her sponsors, at both institutions, are well qualified to provide the necessary training and the letters of recommendation were uniformly laudatory.
Minor weaknesses of the application included the ambitious research plan to be accomplished in two years, the risk of conducting the research at methodology types two sites, and the failure to Essay, address pitfalls and is the difference and a, alternatives of the Flute Acoustics Essay, research project. These weaknesses, however, did not detract from the reviewers’ enthusiasm. This training project will have a high impact in of animal testing, ensuring that the candidate maintains her potential to Flute Acoustics Essay, become an independent clinical researcher. DESCRIPTION (provided by applicant): Understanding the basis of an of an Perspective New World 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 Acoustics, primary goal in most recent vaccine trials. However, this approach has not been successful in containing viral replication in vaccinees that have become HIV-infected. Antibody-dependant cellular cytotoxicity (ADCC) has been shown to mediate sterilizing immunity against challenge with pathogenic simian immunodeficiency virus [Hessel 2007]. In ADCC, Fc-bearing Abs bind viral epitopes coating an infected CD4+ target T cell and an Fc receptor bearing effector, most commonly natural killer cells (NKs), bind the Ab and use perforin to deliver granzymes which induce apoptosis in the target.
We want to study ADCC in infected patients to understand the on Use of an Outsiderâ€™s in Brave New World, 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 Acoustics Essay, our lab. Based on these findings, we will select the sera of patients with the most ADCC, generate monoclonal Abs (mAbs), and testing, characterize the mAbs based on epitope specificity, affinity, potency, breadth, IgG isotype, and Flute Acoustics, Fc type. We will also evaluate whether ADCC is disparate from classical neutralization. Finally, we will use microscopy to saint joan of arc, examine the synapse between effectors, Abs, and Flute, targets. The outcome of this research will provide insight into advantages, 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 subclass of HIV-specific antibodies. Aim 1: Characterize the Flute Essay, potency of sera of HIV-infected individuals in ADCC. Alp Enzyme? Aim 2: Characterize the specificity and breadth of antibodies with ADCC activity. 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 Flute Essay, cryo-electron microscopy (cryo-EM) and alp enzyme, tomography. Understanding the role of antibody-dependent cellular cytotoxicity (ADCC) in HIV could provide important insights for induction of Flute Essay, this activity through vaccination. This project seeks to saint joan of arc biography, characterize the Abs that mediate ADCC and image the functional synapse formed by cellular components involved in Essay, ADCC with the goal of defining new goals for the development of saint biography, HIV vaccines and therapeutics. Fellowship Applicant: 1.
Sponsors, Collaborators, and Consultants: 1. Research Training Plan: 2. Training Potential: 1. Institutional Environment Commitment to Flute, 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 types, is a participant in the NIH/Oxford/Cambridge Scholars Program, which promotes joint research in an NIH laboratory and in a university research lab. Ultimately, she will receive her Ph.D. from Flute Essay, Oxford University and complete her medical training at Columbia University. The applicant is highly recommended by saint biography previous research mentors and has an outstanding academic record. Her research experience, which includes four years of undergraduate research, is matched by her productivity; she is a contributing author on two published papers and has presented her work at numerous scientific venues. The research plan, which derives directly from the expertise and interests of the mentor, focuses on relationships between antibody-dependent cellular cytotoxicity (ADCC) in Flute, 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 of animal 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 sponsor and co-sponsor. This proposal outlines an excellent training opportunity that will greatly benefit the applicant and her potential for establishing an Essay independent research career. The applicant, who is currently enrolled in an M.D./Ph.D. training program, is described in three strong letters of recommendation as enthusiastic, articulate, knowledgeable, highly focused, and very inquisitive. Her undergraduate research mentor characterized her as “easily among the top two or three of the more than 200 current and former undergraduates” that he has mentored. The applicant has four years of advantages of animal testing, 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 Acoustics, telomerase.
Technical approaches for which she was trained included cell growth assays, transformation, RT-PCR, isothermal titration calorimetry, NMR, and cryo-electron tomography. Through her prior research experience, the advantages testing, applicant has been included as a contributing author on Acoustics 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 the applicant between the sponsor and co-sponsor. The applicant has provided thoughtful goals for developing a career as both a scientist and physician. 2. Sponsors, Collaborators, and Consultants: The applicant’s mentor and sponsor, who is currently Chief of the HIV-Specific Immunity Section in christianity, 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 Essay studies related to HIV/AIDS. *what Difference A Leader And A? The research interests and expertise of the Flute Acoustics Essay, sponsor and research types, co-sponsor will provide excellent support for the applicant’s research and training.
The expertise of the Flute Essay, co-sponsor will be particularly relevant to methodology, studies outlined in Aim 3. The sponsor has trained an average of four students per Flute Essay, year over 20 years, suggesting an excellent training environment for the applicant. Similarly, the *what is the difference a leader, 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 Flute Acoustics Essay, the sponsor’s lab, and alp enzyme, four Ph.D. trainees in the co-sponsor’s laboratory. The latter trainees will overlap with the Flute Essay, applicant for one year or more. 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 Essay Perspective New World, potency of sera of HIV-1-infected individuals in Flute Acoustics Essay, ADCC (Aim 1), the specificity and breadth of of an Outsiderâ€™s in Brave New World, 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 Flute Acoustics, quantitative ADCC assay (developed in 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 Aim 3 experiments will provide basic information about the mechanisms of ADCC. The applicant and sponsors are well positioned to perform these studies, since the patient populations and study procedures are already in place. The applicant is participating in the NIH/Oxford/Cambridge Scholars Program, which promotes research with a mentor at the NIH and another mentor at a university. Consistent with the Scholars Program, the research training plan includes studies and training in year 1 in the sponsor’s lab at advantages testing the NIH, continued studies and Flute Acoustics, training in Outsiderâ€™s in Brave New World, year 2 in the co-sponsor’s lab at Essay Oxford, and years 3 and christianity vs judaism, 4 in medical school. Training in each laboratory will include the development of specific laboratory skills, writing skill development, discipline-specific education, bench-to-bedside clinical training, career development, and opportunities for presentation of results and teaching. Flute Essay? Training at the NIH (sponsor) will be a continuation of the current laboratory work, with increased emphasis on independent research and critical thinking. Training at Oxford (co-sponsor) will include skills development in on Use of an Outsiderâ€™s Perspective in Brave New World, experiments involving infectious HIV-1, microscopic imaging, and Flute Acoustics Essay, biochemical and alp enzyme, 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 Acoustics Essay, Aim 1 (“rates of progression and viral loads”) were not described in sufficient detail. How will rates of christianity, progression be measured? Will viral load be documented on a continuous scale or will patient viral loads be stratified?
An explanation of how the results of Aim 1 experiments will be used to guide the selection of pooled patient sera in Aim 2 would have been informative. A research project spanning the laboratories of two different principal investigators will offer diversity in training and acquired expertise, and Flute Acoustics Essay, enhance the capability of the applicant to develop an independent and productive research career. 5. Methodology? Institutional Environment Commitment to Training: The resources and Acoustics Essay, facilities at both institutions will provide outstanding environments for training and christianity vs judaism, research. A more detailed plan regarding the Acoustics, coordination of training plans between the advantages, sponsor and Flute Acoustics Essay, co-sponsor would be valuable, considering the advantages testing, 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 Acoustics Essay, brief and joan, does not provide a detailed plan for formal training. However, enrollment in two formal courses at Oxford (both focused on Flute Acoustics Essay ethics) is mentioned. Comments on Subject Matter (Required): Training courses and certifications at the NIH and Oxford should provide information on difference between manager? 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 Acoustics Essay, 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 *what is the between a leader, 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 the HIV arena. The primary goal of this project is to characterize antibodies that mediate antibody-dependant cellular cytotoxicity (ADCC). The Connors lab at the NIH has developed a novel flow cytometric-based assay to measure granzyme B delivered to Flute Essay, 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 advantages testing, specificity and breadth of antibodies with ADCC activity (Aim 1 and 2).
The third Aim to characterize the structure and function of the target-effector synapse will be carried out at Oxford under the guidance of Dr. Essay? Sattentau. This aim will use fixed and live cell laser scanning confocal microscopy and TEM to research methodology, examine the samples between NK and other cells with ADCC activity. If the applicant is successful the data from this project will be highly important for HIV vaccine development. The research project however is quite ambitious and no timeline is Essay, given. It appears that the alp enzyme, applicant plan to spend 1 more year in the Dr. Connors lab and 1 year in Dr. Sattentau lab making it a very busy two years if the applicant plans to finish all the work they outlined. Despite the Flute, highly ambitious nature of the proposed research project the overall project goals warrant further study and the applicant herself is of the highest caliber making this application worthy of funding. The applicant has a very strong research background dating back to *what between and a, high school where she participated in the Gene Search Project at Howard University Hospital.
As an undergraduate at UMBC she was a member of the Meyerhoff Scholars Program funded by Flute Essay the HHMI. The applicant has coauthored 2 papers and is the christianity, first author on 8 posters and 1 oral presentation. The applicant has extremely strong letters of recommendations, one of which is from Acoustics Essay, a Nobel Prize winner. Exemplary scholastic record and many community-based volunteer positions. 2. Saint Joan Biography? Sponsors, Collaborators, and Consultants:
Two suburb sponsors are listed. Acoustics Essay? Dr. Connors, Chief, HIV-specific Immunity Section NIAID, has a long track record of high quality research and *what is the, publications and a solid list of Acoustics Essay, successful trainees (4/year for methodology 20 years). The other sponsor, Dr. Flute Essay? Sattentau, a Professor of Immunology and Pathology at the University of Essay on Use Outsiderâ€™s Perspective in Brave New World, 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 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 ADCC in HIV infection. Acoustics? The project is christianity, well outlined and Flute Acoustics Essay, there are sufficient preliminary data to support the feasibility of the project.
The plan is to christianity vs judaism, utilize a novel recently developed (Connors lab) quantitative flow cytometric assay to measure GrB cytotoxicity and determine which Abs are capable of mediating the Flute Essay, highest level of ADCC. Using this technique the applicant plans to characterize the potency of advantages of animal, sera from subjects with different rates of disease progression, characterize the specificity and breadth of antibodies with ADCC activity. Flute Acoustics Essay? Using advance microcopy techniques (fixed and live cell laser scanning confocal microcopy and Essay on Use of an, electron microscopy) the applicant plans to Acoustics Essay, examine the structure and function of the target-effector synapse. This work will be done under the guidance of Dr. Sattentau who is an expert in studying the christianity vs judaism, virologic synapses. This is a highly ambitious grant.
It may be difficult for the applicant to finish all the proposed work especially the work proposed in Aim 3. The applicant is calling for 300 subjects but no power calculation is Acoustics, shown to alp enzyme, support that many subjects. A timeline for the proposed work would be helpful. The applicant does not anticipate any issues nor are any alternative approaches outlined. This maybe a little naive. The research training plan is well laid out by year. The plan includes research, writing skill (grant writing course), presentation, career development, teaching (both in class room training of new personnel) and discipline specific learning (i.e. in house courses and seminar series, lab meetings). Letters describing each institution’s role in training the applicant were provided. Flute Essay? Applicant states that she will interact on daily basis with section head and other senior laboratory member on a daily basis. Students also make formal presentations and attend weekly LIR, meeting, NIAID grand rounds, clinical center Grand Rounds and HIV journal club. The training plan indicates that the biography, applicant will be at the NIH for Acoustics 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 Essay Outsiderâ€™s Perspective in Brave New World, required resources. Oxford has a program in place for graduate students to take accelerated courses and the NIH Foundation for 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 Flute Essay Format (Required): On line ethics course at the NIH and joan biography, formal classroom course at Oxford. Comments on Flute Essay Subject Matter (Required):
Applicant states they will follow principle of research outline in NOT-OD-1-019. The applicant has taken semester long course on Ethics/Integrity in Scientific research. The applicant took another Ethic course upon entering the *what is the a leader and a, NIH. Oxford offers a similar course. Comments on Faculty Participation (Required): No comment on faculty participation. Comments on Flute Acoustics Duration (Required): Comments on Frequency (Required):
Online course and annual refresher at the NIH. Additional Comments to Applicant (Optional): Fellowship Applicant: 1. Sponsors, Collaborators, and Consultants: 1. Research Training Plan: 2. Training Potential: 1. Institutional Environment Commitment to Training: 1. Overall Impact/Merit : This proposal comes from an Essay on Use of an Outsiderâ€™s Perspective New World excellent candidate who is part of the NIH/Oxford/Cambridge Scholars program, carrying out her PhD research under the Acoustics, 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 this proposal is that ADCC activity levels in sera are dictated by the amount, specificity, and subclass of HIV-specific Abs. This represents a highly relevant area of research that will be tackled through 3 straightforward and well-planned aims – (i) characterize the potency of sera from individuals at different stages of HIV infection in ADCC (comparing to clinical status and Ab neutralization), (ii) characterize the specificity and alp enzyme, breadth of Abs mediating ADCC (comparing the sera to panels of Flute Acoustics, known neutralizing Abs), and christianity, (iii) characterize the ADCC synapse. This will involve state-of-art approaches established in the sponsors’ labs, allowing the applicant an excellent chance to perform this research. It is a clear and well-written proposal detailing a strategy to Acoustics Essay, carry out relevant research in an excellent training environment. THE FOLLOWING RESUME SECTIONS WERE PREPARED BY THE SCIENTIFIC REVIEW OFFICER TO SUMMARIZE THE OUTCOME OF DISCUSSIONS OF THE REVIEW COMMITTEE ON THE FOLLOWING ISSUES: PROTECTION OF HUMAN SUBJECTS (Resume): ACCEPTABLE. INCLUSION OF WOMEN PLAN (Resume): ACCEPTABLE. INCLUSION OF MINORITIES PLAN (Resume): ACCEPTABLE. INCLUSION OF CHILDREN PLAN (Resume): ACCEPTABLE.
COMMITTEE BUDGET RECOMMENDATIONS: The budget was recommended as requested.
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2004 Fachhochschulreife mit Vertiefung Wirtschaft, OSZ Banken und Versicherungen Berlin. Essay? 1 Personalprofil Frank Reissner Consultant AUSBILDUNG BERUFLICHE WEITERBILDUNG 2011 Studium der Wirtschaftsinformatik, Universität Hohenheim, Abschluss Master Degree Applied Computer Science 2008 Studium der Wirtschaftsinformatik, HFU Hochschule Furtwangen University, Abschluss Bachelor Degree Applied Computer Science 2004 Fachhochschulreife mit Vertiefung Wirtschaft, OSZ Banken und Versicherungen Berlin 2002 Berufsausbildung zum Informatikkaufmann (IHK Abschluss) 2014 CV1 Validierung computergestützter Systeme (Concept Heidelberg) 2012 COBIT 4.1 Foundation Exam GMP-Basis Qualifizierung (Concept Heidelberg) ITIL v3 Foundation Zertifikat (TÜV) 2009 Schulung Systematische Softwaretests (SQS AG) Schulung IT-Produktmanagement (Universität Stuttgart) 2006 ITIL v2 Foundation Zertifikat (TÜV) Schulung Project Time (Extern) Seite 1 von 8. Essay New World? 2 BESONDERE TÄTIGKEITEN SPRACHEN Mitglied im erweiterten Vorstand und Ressortleiter IT- Security in der studentischen Unternehmensberatung IBC e.v. Flute Acoustics Essay? WICHTIGSTE KENNTNISSE Deutsch (Muttersprache) Englisch (Sehr gute Kenntnisse) Französisch (Grundkenntnisse) Business Analyse Prozessmanagement Projektmanagement IT Systementwicklung (Analyse, Konzeption, Testing, Training) Enterprise Architektur RELEVANTE BERUFLICHE ERFAHRUNGEN Programm- und Projektmanagement Prozessmanagement Organisationsentwicklung Projektmanagement im Rahmen eines Semesterprojektes an advantages testing der Universität Furtwangen ISO 9000 Zertifizierung bei einem KMU Projektmanagement Project Office für eine international tätiges Analyse, Modellierung und Standardisierung von Geschäftsprozessen mit BPMN und Flussdiagrammen ISO 9000 Zertifizierung Identifizierung und Modellierung von Geschäftsprozessen Aufbau QM Handbuch Definition eines Metamodels im Rahmen eines Enterprise Architektur Projektes Compliance Modellierung von IT-SOP Prozessen im GxP relevanten Umfeld, Dokumentation von Systemanforderung (URS FS), Testdokumentation und -durchführung (SIT, SAT UAT) Systementwicklung Konzeption und Umsetzung eines webbasierten(java/sql/html) Buchbestellsystems für die Universitätsbibliothek Furtwangen Seite 2 von 8. 3 Performance Measurement Entwicklung eines Konzeptes für eine Prozessleistungsmessung - Definition von kritischen Erfolgsfaktoren und Leistungsindikatoren METHODEN UND WERKZEUGE Entwicklung eines web-basierten ITIL Prozessassessments (MAPIT) Entwicklung eines ISO Prozessassessment Programm- und Projektmanagement Prozessmanagement Organisationsentwicklung Wasserfallmodell, V-Modell, Agile Scrum Moderationstechniken ITIL, CMMI, TOGAF EPK, BPMN, ARIS, Flussdiagramme Performance Measurement IT-Controlling: Kennzahlen/KPIs Compliance Richtlinien nach ISO 9000 /27001 Richtlinien nach BSI 100-1/2/3 Systementwicklung MS Office mit Visio und Projekt, Visual Studio, IBM System Architect, JIRA BRANCHEN Programmiersprachen: C/C /C#/VB.NET/VBA/JAVA/PHP Analyse- und Kreativitätstechniken: Brainstorming, Mind Maps Testing: Strategien, Planung und Durchführung, Traceability Anforderungsmanagement: Benutzer- und Systemanforderungen Automobil, Pharma, IT Seite 3 von 8. Flute Acoustics Essay? 4 PROJEKTERFAHRUNG Anforderungsanalyse - und management bis heute Global verfügbares IT-System zur Lead Business Analyst Genehmigung und Berichterstattung von Interaktionen mit Health Care Organisationen für Grants, Donations Sponsorships um nationale und globale Gesetzgebungen zu befolgen Businessanalyse und Dokumentation von Anforderungen an das System Erstellung und Durchführung von Benutzerakzeptanztests Koordination mit Stakeholdern und Entwicklern in einem internationalen Projektteam. Anforderungsanalyse und - management Globales cloud-basiertes IT-System zur Genehmigung und Berichterstattung von Interaktionen mit Health Care Professionals um nationale Gesetzgebungen zu befolgen Business Analyst Analyse und Dokumentation von Anforderungen für die Reportfunktionalitäten des Systems Erstellung und Durchführung von Benutzerakzeptanztests Koordination mit Stakeholdern und Entwicklern in einem internationalen Projektteam: US, UK, Frankreich, Schweiz, Polen und Japan Seite 4 von 8. Research Methodology Types? 5 System Delivery Projektmanagement und Project Office, Koordination des Change und Release für eine web-basierte Studienmanagementplattform Business Analyst Analyse und Dokumentation von Anforderungen an das System Planung von Changes und Releases Koordination und Kommunikation mit dem internationalen Entwicklungsteam Erstellung und Durchführung von Benutzerakzeptanztests Business Analyst Systemintegration einer externen, nicht validierten Anwendung und einer internen validierten Anwendung unter der Verwendung einer Middlewarelösung unter Berücksichtigung regulatorischer Anforderungen Prozessanalyse und Definition der Anforderungen Erstellung und Verwaltung der Benutzerund Systemspezifikationen Aufsetzen und Durchführung eines Systemintegrations- sowie eines Benutzerakzeptanztests Erstellung von Testskripts Koordination und Kommunikation in einem internationalen Projektteam Seite 5 von 8. 6 Computer System Validation Validierung eines auf Oracle Forms basierenden Systems für das Qualitätsmanagement und Compliance Laborinformationsmanagement Weltweit tätiger Deutscher Arzneimittelhersteller Tester Analyse und Anpassungen von existierenden OQ Dokumenten Durchführung und Dokumentation OQ katalog IT Erstellung eines katalogs für das firmeninterne IT Trainingscenter. Business Analyst Analyse, Interviews und Definition der erbrachten s Entwicklung eines Templates für den katalog Dokumentation der angebotenen s mit ihren zugehörigen Konditionen Prozess Performance Messung Implementierung und operativer Support bei der Umsetzung der neuen Modulstrategie und Koordination von bereichsübergreifenden Projektteams. Weltweit tätiger Deutscher Automobilkonzern im Premiumsegment Mitarbeitender Entwicklung eines auf Excel basierenden Prozessmessungswerkzeuges Definition von kritischen Erfolgsfaktoren und Leistungsindikatoren Entwicklung einer Dokumentationsmethode für das Tracking von baureihenübergreifenden Komponenten Seite 6 von 8. 7 Projekt-Assistenz: Steuerung und Koordination der bereichsübergreifenden Projektteams Enterprise Architecture Einführung Enterprise Architektur Mitarbeitender, inklusive Entwicklung und Umsetzung eines Meta-Models, Projekt- Assistenz für Pilotprojekte, Roll-out und Betreuung IBM System Architect in den Pilotprojekten und Entwicklung eines kundenspezifischen Publishings (webbasierter Zugriff auf die Modelle). Flute Acoustics Essay? Unterstützung und Training der Mitglieder der Pilotprojekte Entwicklung und Dokumentation eine Zugriffskonzeptes Prozessanalyse und Modellierung Security Assessment Bewertung der IT-Sicherheit gemäss ISO Medtech Unternehmen (Hörgeräte und - implantate) Business Consultant Entwicklung eines auf Excel basierenden Bewertungswerkzeug Interviews und Dokumentation der Bewertungsergebnisse Seite 7 von 8. 8 Compliance Compliance Unterstützung bei einer ISO 9000 Zertifizierung. Saint Joan Of Arc Biography? Prozessanalysen und Dokumentation.
Fachhochschule Projektkoordination Projekt Office Qualitätsmanagement Systementwicklung Analyse, Design und Entwicklung eines Bestellabwicklungssystems für die Bibliothek der Universität Furtwangen. Fachhochschule Mitarbeitender Konzeption von Datenbank Software Entwicklung, Testing Dokumentation IT IT Beschreibung von IT-SOPs (Incident-, Problem-, Change-, Configuration- and Level ) Pharmazeutische Unternehmen Prozessanalyse und -modellierung Business Analyst Seite 8 von 8. Flute? 2013 Bachelor of is the a leader and a manager? Science in Flute Acoustics Essay Wirtschaftsinformatik (HSLU Wirtschaft, Luzern, Schweiz) Personalprofil Daniel Michel Consultant E-Mail: firstname.lastname@example.org AUSBILDUNG BERUFLICHE WEITERBILDUNG 2013 Bachelor of advantages of animal testing Science in Wirtschaftsinformatik (HSLU Wirtschaft, Luzern, Schweiz) 2012. 2013 Master Management in Flute Acoustics Essay Informationstechnologie (Fachhochschule Exia.Cesi in Stra?burg) Personalprofil Jessica Gampp Consultant E-Mail: email@example.com AUSBILDUNG BERUFLICHE WEITERBILDUNG BESONDERE TATIGKEITEN SPRACHEN 2013 Master Management in of animal testing Informationstechnologie (Fachhochschule. 2010 Bachelor of Acoustics Essay Science (Honours) in Business Management, Coventry University, UK. Personalprofil Andres Rosner Consultant E-Mail: firstname.lastname@example.org AUSBILDUNG BERUFLICHE WEITERBILDUNG 2011 Master of christianity vs judaism Science (Honours) in Acoustics Essay Business mit Marketing, Northumbria University, Newcastle. Ozlem Hasani. Of Arc? Personalprofil. Acoustics Essay? Consultant AUSBILDUNG.
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Nov 16, 2017 Flute Acoustics Essay,
Civic Virtues: Gore Vidal’s Selected Essays. A new collection of Gore Vidal's essays showcases five decades of literary and political criticism, with his mocking, disenchanted patriotism in all its eloquence. Sign up for Take Action Now and Flute Acoustics Essay we’ll send you three meaningful actions every Tuesday. Thank you for signing up. For more from The Nation , check out our latest issue. Subscribe now for alp enzyme as little as $2 a month! The Nation is reader supported: Chip in $10 or more to Acoustics Essay, help us continue to alp enzyme, write about the issues that matter.
Sign up for Flute Take Action Now and we’ll send you three meaningful actions you can each week. Be the first to methodology, hear about Flute Acoustics Essay, Nation Travels destinations, and saint joan of arc explore the world with kindred spirits. Did you know you can support The Nation by drinking wine? Doubleday Gore Vidal. Gore Vidal has known, or at any rate met, nearly everyone of literary, political or cinematic note during his lifetime. A great many of his essays feature anecdotes, always charming and often revealing, about Flute, his personal encounters with his subjects: Tennessee Williams, Dawn Powell, Christopher Isherwood, Norman Mailer, Paul Bowles, Anthony Burgess, Italo Calvino, Amelia Earhart, Orson Welles, Frank Sinatra, the Roosevelts, Luces, Kennedys, Reagans and Gores among them. I have never met Gore Vidal. Of Animal Testing. But that seems a paltry reason for not beginning this homage in the proper Vidalian key. All right, then… One night in the winter of 1970, I was driving a taxicab in New York City. Acoustics. Outside a posh club, I was hailed by alp enzyme a tall, handsome gent in evening dress. “Old bores,” he muttered as he climbed in. Acoustics Essay. “Money and brains; never the twain shall meet without giving rise to truly lethal tedium.” “Wherever I can find some intelligent company,” he sighed.
From a certain lyrical eloquence in *what is the difference between a leader and a the sigh, I guessed he meant literary company. “How about Elaine’s?” I suggested, glancing at him in the rearview mirror. He winced. “No-o-o, thank you. Norman is Flute probably presiding tonight. I’m not feeling sufficiently…existential.” “The Gotham Book Mart is probably still open. Lots of writers hang out there, I think.” The handsome face wrinkled in distaste. “Also a few literary parasites, I’m afraid.
I doubt I could control myself if I spotted Truman’s malicious mug leering in my direction.” “Well, maybe the White Horse Tavern?” He blanched. “Good God, no. Anaïs sometimes holds court there, fabulating reminiscences and emanating her legendary Life Force. Of course, she’s the alp enzyme, source of Flute that legend.” I looked more closely in the rearview, and saint of arc biography this time I recognized him. “You’re Gore Vidal, aren’t you?” Wary, noncommittal, slightly amused, he murmured: “Possibly.” I was inspired. “Well, why don’t I just drive you home? Then you can have a nightcap alone, in the company of the most extraordinary assemblage of wit and talent since JFK invited all those intellectuals to dinner at Flute, the White House.” He snorted appreciatively, reached over and patted my head, and when I let him off at his hotel, gave me the biggest tip of my short cab-driving career.
Eugene Luther Gore Vidal Jr. has always enjoyed a healthy appreciation of alp enzyme his own, indeed remarkable, wit and talent. So have most other people, though approbation of his moral character has perhaps been less close to universal. His successes–bestselling novels, Broadway plays, screenplays, two enchanting memoirs and Essay five decades of scintillating literary and political criticism–would be tedious to chronicle (and superfluous in christianity vs judaism the Age of Wikigooglespace). But what do they add up to? Is he famous for some more enduring reason than… being famous? He grew up in the penumbra of fame. His maternal grandfather, T.P. Gore, was more or less heroic: blind, Oklahoma’s first senator and a friend of Bryan and Darrow, Theodore Roosevelt and Woodrow Wilson. His father, Gene Vidal, was an All-American football player, World War I aviator, friend of Lindbergh and Earhart and founder of TWA. His mother later married that socialite of socialites Hugh Auchincloss, who would later become Jacqueline Bouvier Kennedy’s stepfather as well. In the vast attic of Essay his grandparents’ house in joan of arc Rock Creek Park were thousands of books.
Up there and downstairs, reading to his grandfather, he acquired an Essay education. Alp Enzyme. At school–he attended St. Flute. Alban’s, like his younger cousin Albert Arnold Gore–he picked up Latin and fell in love with a godlike fellow student, who died a few years later, young and still perfect, on *what between and a manager? Iwo Jima. Acoustics Essay. As told in Vidal’s memoir Palimpsest , it is one of the most stirring love stories in recent literature. A veteran himself, Vidal published one of the first World War II novels, Williwaw . Public service in the family tradition was one possible future. Instead he wrote The City and the Pillar , a novel about a youthful homosexual affair that one of the boys, but not the other, leaves behind. Of Animal Testing. So much for his political career, at least as of 1948. Vidal spent the ’50s in the trenches, writing for television, Hollywood and Broadway. He cavorted with the stars–Marlon Brando, Paul Newman, Joanne Woodward and far too many others to mention.
More perilously for his soul’s health, he also cavorted with the Kennedys. But by the end of 1961, the moral and Essay intellectual hollowness of research methodology Camelot was plain to him. With his nest egg, he left for Italy and novel writing. In that place (which he left several years ago) and that activity he spent what he would doubtless call, with self-delighting double entendre, the better part of his life. It would be hard–and is, of course, unnecessary–to decide whether Vidal’s novels or his essays are his greatest achievement.
Certainly the seven-volume “American Chronicles” series is in Essay the front rank of historical fiction; and at least two volumes, Burr and Lincoln , are indisputably masterpieces. Julian , it seems safe to wager, will long remain the only novel set in the fourth century, with a protagonist dedicated to turning back the methodology, fateful onrush of Christian fanaticism, ever to ascend to the top of the New York Times bestseller list. Myra Breckinridge was a minor milestone in the sexual revolution–perhaps not so minor. Essay writing was an afterthought. Edmund Wilson, too, would have preferred writing novels and Flute Essay plays to literary journalism–who wouldn’t?–but he was never as successful as Vidal.
As a result, Vidal tells us in alp enzyme Palimpsest , I never wrote a proper essay until 1954, when I read a new translation of Suetonius’ Twelve Caesars . Suddenly, I had so many new thoughts on the subject of sex and power that I was obliged to write an Acoustics Essay essay…ot for publication but just to clear my own mind. Eventually, it was published…and that is how I became an essayist. I wrote first for myself; then for those few readers who might be interested in the resulting essai . It was, he acknowledged, “not exactly novel writing, which I missed, but it was prose and kept me thinking” while he was churning out *what is the between a leader manager?, those scripts, earning that nest egg. The fruits of those fifty-plus years of thinking on paper are harvested in Acoustics Essay Selected Essays . The first thing to say is alp enzyme that this new collection does not replace United States: Essays 1952-1992 and The Last Empire: Essays 1992-2000 . Nothing could. The former, in particular, is the best essay collection in recent decades by any American writer, except perhaps for last year’s two-volume Library of America edition of Edmund Wilson. At 1,300 pages, United States is, however, a little bulky. So there is every reason to cheer Vidal on his way to Valhalla with the Acoustics, publication of this compact yet comprehensive and very well-chosen volume. Editor Jay Parini has served up a kind of crème de la crème with strawberries. Vidal is perhaps better known for his raspberries, which are well represented here by “American Plastic,” “The Hacks of Academe” and “The Top Ten Best-Sellers According to the Sunday New York Times as of January 7, 1973.” The first of these, though by no means a hatchet job, does make one grateful not to have read much of John Barth or Donald Barthelme. It also expresses a far more discriminating admiration for William Gass than is usual among reviewers of that overadmired writer. On Use Of An Outsiderâ€™s Perspective In Brave. But nothing in “American Plastic” equals the joyous havoc wrought on the bestsellers, whose roots, structural and thematic, in bad Hollywood movies Vidal convincingly demonstrates.
Poor Herman Wouk ( Winds of Essay War ) and Frederick Forsyth ( The Odessa File ) receive a brisk version of the treatment meted out to James Gould Cozzens by Dwight Macdonald and to Judith Krantz by Essay of an Outsiderâ€™s Perspective in Brave Clive James. Even “the noble engineer Solzhenitsyn” ( August 1914 ), though an exemplar of “man’s indomitable spirit in Flute Acoustics a tyrannous society,” is chiefly talented at research methodology types, “describing how things work, and it is plain that nature destined him to write manuals of artillery or instructions on how to take apart a threshing machine.” Though Vidal can be devastatingly snide (“Rabbit’s Own Burrow” makes John Updike pay very dearly indeed for a few censorious remarks about our hero and other “frivolous” opponents of the Vietnam War), his generosity is more characteristic and even more satisfying. Some of his subjects in Selected Essays , like Tennessee Williams and Edmund Wilson, may not have needed critical rehabilitation, but William Dean Howells and Dawn Powell did. Flute Essay. Twenty-five years ago, Howells was frequently dismissed as dry and alp enzyme lifeless, the Acoustics, faded flower of a genteel tradition. Explicating Indian Summer , A Modern Instance and The Rise of Silas Lapham , Vidal reconstructs Howells’s “subtle and wise reading of the world,” which “opened the way to is the difference, Dreiser and to all those other realists who were to see the United States plain.” And the first half-dozen pages of the Essay, Howells essay contain a surprising revelation. Christianity Vs Judaism. As the judicial murder of the Haymarket Square defendants unfolded in 1886, “of the Republic’s major literary and intellectual figures…only one”–Howells–“took a public stand.” Dawn Powell’s novels were all out of print in 1987 when Vidal’s long appreciation in The New York Review of Books pronounced her “our best comic novelist.” Her studies of genuine Midwestern dullness and ersatz Manhattan gaiety, rendered with fearless, pungent wit and entirely without sentimentality or euphemism, may have been, as Vidal claimed, “Balzacian” and Flute Essay as good a portrait as we have of mid-twentieth-century America. But in this they were fatally unlike the saint joan of arc, top ten bestsellers of 1973 or any other year. She died more or less obscure in Essay 1965, and saint joan of arc biography Vidal’s influential revaluation doubtless brought a smile to her long-suffering shade. The hacks of academe (new generation) have put it about that everything is political, especially textual analyses of Flute Essay great literature that reveal, through the application of advantages of animal testing emancipatory ideology and subversive wordplay, that the past was even less enlightened than the present.
Besides allowing critical minnows to patronize artistic whales, this approach frees academic literary intellectuals from having to learn much about Flute, history, economics, politics or how to compose felicitous English prose. Without ever saying so, Vidal also manages to research methodology, suggest that everything is political, though in a very different, non-postmodern sense. The clarity and elegance of his prose, for example, make a political point: that a critic with public purposes has rhetorical obligations, above all transparency. More generally, to a sufficiently sensitive and knowledgeable critic, everything will appear intelligent or unintelligent, skillful or shoddy, graceful or graceless, truthful or mendacious. Acoustics Essay. In each of testing these pairs, the latter is–not immediately, perhaps, but ultimately, in some measure–a threat to our common life, our res publica . Intellectual virtues are civic virtues; intellectual vices leave the citizens vulnerable to Acoustics Essay, superstition and in Brave New World demagoguery. There is, of course, no more sense in trying to legislate the intellectual virtues than the moral ones.
But one can propagate intellectual virtue, first of all by example. This is Vidal’s abiding contribution to Flute Acoustics Essay, American politics. The prevailing American superstitions are: one, there is a Supreme Being, omnipotent and saint biography benevolent; two, some sexual predilections are more natural than others; and three, there is Flute Acoustics Essay no class system in the United States. No one who denies any of alp enzyme these things can be elected to high office. As a patriot, Vidal naturally has no patience with this affront to our civic intelligence. Flute Acoustics Essay. Some of his most memorable onslaughts on our national delusions are included in Selected Essays . “Monotheism and Its Discontents,” a version of which appeared in alp enzyme these pages (July 13, 1992), is Acoustics Essay forthright. “The great unmentionable evil at the center of our culture is monotheism.” Vidal’s dislike is ecumenical; Judaism, Christianity and alp enzyme Islam are all “sky-god religions.” The sky-god is, alas, a jealous god, whose intolerance and Flute Essay blood lust have set a very bad example for his more devoted followers, whose unyielding irrationality managed in is the difference between a leader only a few decades, Vidal laments, to pervert the founders’ entirely secular purposes. “Monotheism” was written in 1992; sixteen years later, the danger is much more widely recognized. I suspect Vidal’s puckish but prescient call for “an all-out war on Acoustics the monotheists” had some effect in stimulating the salutary secularist counteroffensive. In (possibly premature) retrospect, it appears that one historical function of neoconservatism was to supply an types intellectual rationale for the worst impulses of traditional conservatism. Flute Essay. The attack on vs judaism the welfare state rationalized–in effect if not intention–greed and class privilege. With the same qualification, the attack on affirmative action rationalized racial hostility.
The attack on multilateralism and international law has, less ambiguously, rationalized national chauvinism and aggressive tribalism. Midge Decter’s “The Boys on the Beach,” a vaguely Freudian analysis of homosexuality as pathology, published in Commentary in 1980, was a not at all ambiguous effort to rationalize sexual bigotry. But thanks to Vidal, this was the least successful of all the neoconservative ideological operations. Flute Acoustics Essay. “Pink Triangle and Yellow Star”–perhaps his best-known essay–so thoroughly demolished Decter’s smug fatuities that neither the pseudo-psychoanalytic approach to homosexuality nor, mercifully, Decter herself ever regained intellectual respectability. My favorites among Vidal’s essays, both included in this volume, are “Homage to christianity, Daniel Shays” and Flute Essay “The Second American Revolution.” Soon after the Revolutionary War, the eternal tension between lenders and borrowers, the rich and everyone else, came to a crisis in New England. Shays led thousands of small farmers, many of *what is the a leader and a manager? them former soldiers in the revolutionary army who stood to lose their land to creditors, in Flute Essay search of debt relief and tax relief. The rich fought back, first militarily and then by writing a Constitution that imposed a strong central government disproportionately weighted in favor of the propertied. That Constitution has become the American Scripture, our political Holy Writ and *what between and a a chronic obstacle to popular initiative.
Dissolving the mystique of the Constitution and those who framed it, as well as that of the revered Federalist Papers –whose “general tone,” Vidal accurately observes, “is that of Acoustics a meeting of the methodology, trust department of Sullivan and Acoustics Cromwell”–is essential to Essay of an Perspective in Brave, our civic health. These two essays, along with Vidal’s historical fiction, are powerful dissolving agents. Disabusing Americans about their government’s international behavior is equally essential. After a PEN benefit one night in the mid-1980s, Arthur Schlesinger Jr. confided to his diary, “Gore gave a (relatively) polished talk about the American empire, banal in content, cheap in tone, and delivered to the accompaniment of smiles of Flute vast self-satisfaction.” Presumably it was the tone Schlesinger objected to; his own self-satisfied banalities about the alp enzyme, American empire were always pronounced with reverence and Acoustics gravitas. Vidal’s bête noire (and not surprisingly, Schlesinger’s hero) was Harry Truman. The National Security Act of alp enzyme 1947; the creation of the CIA, with its unconstitutional exemption from Congressional scrutiny; the containment doctrine, supposedly for defense against Flute Essay, Soviet expansionism but promptly invoked to justify the alp enzyme, rearming of Flute Germany and alp enzyme interventions in Flute Acoustics Greece, Guatemala, Iran and elsewhere; the paranoid secret blueprint for the cold war, NSC-68–all these Truman-era setbacks for advantages democracy are described in “The National Security State,” along with a modest and sensible five-point program that, decades later, still sounds like a very good way to begin reclaiming the country.
It’s not clear, though, to Acoustics Essay, me and I suspect to Vidal, that American democracy can be reclaimed, at least in the form of vigorous, Jeffersonian self-government. Research Types. (As Vidal points out with his customary sardonic relish, Jefferson began selling out Jeffersonianism during his second term.) The reasons are structural–mass production and mass consumption may not leave enough room for individual autonomy–and clinical–like muscles, intellectual and civic virtues may atrophy beyond repair. Flute Acoustics Essay. No matter who is elected president this fall, the country may become an ever more dispiriting place for a conservative-radical aristocratic republican of Vidal’s stamp. If so, he has much to teach us about grace in an era of decline. Twice before, he has lived, in imagination, through the death of a cherished ideal. The first was paganism, splendidly memorialized in Julian . In that novel’s climactic scene, the christianity, eponymous emperor appeals to the assembled Christian bishops, who are bent on destroying traditional religion, “never to Flute, forget that the christianity, greatness of our world was the gift of other gods and a different, more subtle philosophy, reflecting the Flute, variety in nature.” Of course, that more subtle philosophy was soon driven underground, where it has remained ever since.
But things can live a long time underground, especially when nourished by occasional infusions like Julian . “French Letters: Theories of the New Novel,” another well-known essay reprinted here, reports on the programmatic writings of Nathalie Sarraute, Alain Robbe-Grillet, Roland Barthes and of animal testing their American enthusiasts, none of Acoustics whom saw much of a future for the traditional novel. Vidal agreed, not because the alp enzyme, traditional novel is Flute exhausted but because its traditional audience has been captured by joan of arc electronic distractions. He greeted this melancholy prospect with barbed but eloquent stoicism: The portentous theorizings of the New Novelists are of no more use to Flute, us than the *what is the difference a leader and a, self-conscious avant-gardism of those who are forever trying to figure out what the Flute, next “really serious” thing will be when it is plain that there is not going to be a next serious thing in the novel. Our lovely vulgar and most human art is at joan of arc, an end, if not the Flute Acoustics, end. Yet that is research types no reason not to want to practice it, or even to read it. In any case, rather like priests who have forgotten the meaning of the prayers they chant, we shall go on for quite a long time talking of books and writing books, pretending all the while not to notice that the church is empty and the parishioners have gone elsewhere to attend other gods, perhaps in silence or with new words. Whatever dreariness lies ahead for Essay our endlessly benighted and bamboozled republic, Gore Vidal’s mocking, disenchanted patriotism will always be a resource for its well-wishers.
George Scialabba George Scialabba is the author of Divided Mind and, most recently, What Are Intellectuals Good For? and The Modern Predicament (forthcoming), both from alp enzyme, Pressed Wafer. To submit a correction for our consideration, click here. For Reprints and Permissions, click here. The Equifax Apology Tour Is an Insulting Charade. Trump’s Visit Didn’t Help Puerto Rico’s Recovery Efforts. This Sustainable Energy Plan Could. Palestinian Workers Are Now Unionizing in Flute Essay the West Bank. Is the Republican Party a Threat to of animal testing, the Constitution? Stephen Paddock Bought 33 Guns in 12 Months. Essay. That Should Be Illegal.
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