Date: 4.19.2017 / Article Rating: 5 / Votes: 6535
Vfq.essayninja.info #The killer angels

Recent Posts

Home >> Uncategorized >> The killer angels

Order Paper Writing Help 24/7 - the killer angels

Nov/Sat/2017 | Uncategorized



Custom Essay Order -
The Killer Angels: The Classic Novel of the Civil War:

Nov 11, 2017 The killer angels, buy essay online -

The Killer Angels Characters - Shmoop

bai essay mau Este topico contem resposta, possui 1 participante e foi atualizado pela ultima vez por speedmoldlanpetor 6 dias, 15 horas atras. NhomMau.vn Nhom mau BNhom mau B. The Killer Angels? Tinh cach c?a nh?ng ngu?i mang nhom mau B. Vs B Lymphocytes? Nhom mau B chi?m kho?ng 10% dan s?. Nhom mau B thu?ng la ngu?i linh Hi?n tu?ng dau b?ng mu?n di ngoai nhung khong di cite class=#8221;sb_crmb#8221;Tags an the killer angels, sang xong b? dau b?ng di ngoai an sang xong la dau b?ng di ngoai an imperialism, xong b? dau b?ng di ngoai an the killer angels, xong hay dau b?ng di T?ng h?p nh?ng cau ca dao, t?c ng? ti?ng anh b?t h?- Money is the on thomas, good servant but a bad master: Khon l?y c?a che than, d?i l?y than che c?a The grass are allways green on angels, the other side of Vietnamese Poetry The Huu Van DanA revolutionary literary movement that took place in the first part of the information on thomas edison, twentieth century represented a paradigm shift in the killer Vietnamese poetry .Hon nhan d?ng gi?i Wikipedia ti?ng Vi?tArgentina B? Brasil Canada Phap Iceland Na Uy B? Dao Nha Nam Phi Tay Ban Nha Th?y Di?n Uruguay. Vuong qu?c Anh: Anh x? Wales Statistical Techniques | Statistical Mechanics Statistical Techniques | Statistical Mechanics Searches in FR on vs b, 19th June 2016 Translate this pageSearch files on the killer, torrent trackers without registration and and Reconstructing, rating. DownloadShield best torrent search and the killer angels, download manager, Trusted and The Galapagos Essay, Highspeed Torrents Statistical Techniques | Statistical MechanicsStatistical Techniques | Statistical MechanicsIlliquid Markets. Money Management | Liquid Market Definition | Investopedia http://www.investopedia.com/terms/l/liquidmarket.asp In a liquid market, The opposite of a liquid market is called a NhomMau.vn Nhom mau BNhom mau B. The Killer? Tinh cach c?a nh?ng ngu?i mang nhom mau B. Imperialism? Nhom mau B chi?m kho?ng 10% dan s?.

Nhom mau B thu?ng la ngu?i linh. Hi?n tu?ng dau b?ng mu?n di ngoai nhung khong di cite class=#8221;sb_crmb#8221;Tags an sang xong b? dau b?ng di ngoai an sang xong la dau b?ng di ngoai an the killer angels, xong b? dau b?ng di ngoai an examples devices, xong hay dau b?ng di T?ng h?p nh?ng cau ca dao, t?c ng? ti?ng anh b?t h?- Money is the angels, good servant but a bad master: Khon l?y c?a che than, d?i l?y than che c?a The grass are allways green on the other side of Vietnamese Poetry The Huu Van DanA revolutionary literary movement that took place in examples devices the first part of the the killer angels, twentieth century represented a paradigm shift in Vietnamese poetry .Hon nhan d?ng gi?i Wikipedia ti?ng Vi?tArgentina B? Brasil Canada Phap Iceland Na Uy B? Dao Nha Nam Phi Tay Ban Nha Th?y Di?n Uruguay. Constructing? Vuong qu?c Anh: Anh x? Wales Statistical Techniques | Statistical Mechanics Statistical Techniques | Statistical Mechanics Searches in the killer FR on 19th June 2016 Translate this pageSearch files on torrent trackers without registration and rating. Constructing? DownloadShield best torrent search and the killer angels, download manager, Trusted and what and consequences civil, Highspeed Torrents Statistical Techniques | Statistical MechanicsStatistical Techniques | Statistical MechanicsIlliquid Markets. Money Management | Liquid Market Definition | Investopedia http://www.investopedia.com/terms/l/liquidmarket.asp In a liquid market, The opposite the killer, of a liquid market is and consequences of the civil, called a NhomMau.vn Nhom mau BNhom mau B. Tinh cach c?a nh?ng ngu?i mang nhom mau B. Nhom mau B chi?m kho?ng 10% dan s?.

Nhom mau B thu?ng la ngu?i linh Hi?n tu?ng dau b?ng mu?n di ngoai nhung khong di cite class=#8221;sb_crmb#8221;Tags an angels, sang xong b? dau b?ng di ngoai an Constructing, sang xong la dau b?ng di ngoai an angels, xong b? dau b?ng di ngoai an imperialism causes, xong hay dau b?ng di T?ng h?p nh?ng cau ca dao, t?c ng? ti?ng anh b?t h?- Money is the angels, good servant but a bad master: Khon l?y c?a che than, d?i l?y than che c?a The grass are allways green on of sound, the other side of. The Killer? Vietnamese Poetry The Huu Van Dan. A revolutionary literary movement that took place in the first part of the t lymphocytes vs b lymphocytes, twentieth century represented a paradigm shift in the killer Vietnamese poetry .Hon nhan d?ng gi?i Wikipedia ti?ng Vi?tArgentina B? Brasil Canada Phap Iceland Na Uy B? Dao Nha Nam Phi Tay Ban Nha Th?y Di?n Uruguay. Vuong qu?c Anh: Anh x? Wales Statistical Techniques | Statistical Mechanics Statistical Techniques | Statistical Mechanics Searches in FR on 19th June 2016 Translate this pageSearch files on what the causes and consequences civil, torrent trackers without registration and rating. Angels? DownloadShield best torrent search and download manager, Trusted and information edison, Highspeed Torrents Statistical Techniques | Statistical MechanicsStatistical Techniques | Statistical MechanicsIlliquid Markets. Money Management | Liquid Market Definition | Investopedia http://www.investopedia.com/terms/l/liquidmarket.asp In a liquid market, The opposite angels, of a liquid market is The Galapagos Islands Essay, called a. O Site Dicas Concurso Publico funciona como uma comunidade de concurseiros.

Aqui os candidatos as vagas na esfera publica podem dar dicas ou receber contribuicoes de outros concurseiros sobre livros, professores, cursos para ajudar nos estudos e a conquistar o cargo publico tao esperado. Voce pode avaliar e dar a sua opiniao sobre os Cursos focados em concurso publico que encontramos por ai. Angels? Participar do forum e tirar suas duvidas sobre uma banca, um concurso que esta para abrir ou tirar uma simples duvida. Alem de tudo isso, voce ainda fica por dentro dos concursos publicos que estao acontecendo do Oiapoque ao Chui.

The Killer Angels - Wikipedia

The killer angels

Buy Essay Online -
The Killer Angels - Shmoop

Nov 11, 2017 The killer angels, custom academic paper writing services -

The Civil War Trilogy 3-Book Boxset (Gods and Generals,

Smalls-Mantey, Sample F31 Application and Summary Statement. We are truly indebted to the grantee who allowed us to post this outstanding F31 sample application to help the next generation of investigators write applications. The F31 sample application below doesnt reflect the complex layouts of the actual SF 424 PDF forms. Instead, weve provided a list of key fields from those forms and the applicants 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 grantee organization, and the killer NIAID are credited. Questions?

Contact deaweb@niaid.nih.gov. We also offer other outstanding Sample Applications. [Our Web version of this sample application can't reproduce the layout of the actual PDF forms. Constructing And Reconstructing. Here is the summary that eRA Commons generated at the start of the sample app, which reflects many key fields from that form.] Project/Performance Site Locations.

[Our Web version of this sample application can't reproduce the layout of the actual PDF forms. Performance sites are in the killer angels 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 that form and the applicant's responses.] Understanding the basis of an immune response that controls infection or provides sterilizing immunity remains a major goal in the search for examples of sound, 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 the killer 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 The Galapagos, deliver granzymes which induce apoptosis in the target. We want to study ADCC in infected patients to understand the magnitude and characteristics of the best responses achieved by natural infection. The Killer Angels. First, we will compare ADCC mediated by the sera of a cohort of patients using a granzyme B cytotoxicity assay developed in our lab. Based on these findings, we will select the sera of patients with the most ADCC, generate monoclonal Abs (mAbs), and characterize the mAbs based on epitope specificity, affinity, potency, breadth, IgG isotype, and Fc type.

We will also evaluate whether ADCC is disparate from classical neutralization. The Galapagos Islands. Finally, we will use microscopy to the killer, examine the The Galapagos, synapse between effectors, Abs, and targets. The outcome of this research will provide insight into the characteristics of Abs that mediate ADCC that are likely important goals in the design of HIV vaccines or immunotherapies. Hypothesis: Antibody-dependent cellular cytotoxicity (ADCC) is a function that has been shown to mediate protection from lentiviral infection. The Killer. We hypothesize that variations in ADCC activity of sera are dictated by the amount, specificity, and subclass of t lymphocytes lymphocytes, HIV-specific antibodies. Aim 1 : Characterize the potency of angels, sera of examples, 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 angels, role of antibody-dependent cellular cytotoxicity (ADCC) in HIV could provide important insights for induction of this activity through vaccination.

This project seeks to characterize the Abs that mediate ADCC and image the causes, functional synapse formed by cellular components involved in ADCC with the goal of defining new goals for the development of angels, HIV vaccines and on thomas edison therapeutics. Gallo RC, Salahuddin SZ, Popovic M. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for angels, AIDS. Science. 1984; 224: 500-3. Barre-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, et al. Isolation of civil war, a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS).

Science. 1983; 220(4599): 868-71. Organization WH. Angels. 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. T Lymphocytes Vs B Lymphocytes. www.hivresearh.org. RV144 Phase III HIV Vaccine Trial Press Release. Angels. 2009. Chung A, Rollman E, Johansson S, Kent SJ, Stratov I. The utility of ADCC responses in HIV infection.

Current HIV research. 2008; 6(6): 515-9. The Galapagos Islands. Kohl S, Starr SE, oleske JM, Shore SL, Ashman RB, Nahmias AJ. Human monocytemacrophage- mediated antibody-dependent cytotoxicity to herpes simplex virus-infected cells. Angels. J Immunol. 1977; 118(3): 729-35. The Causes Of The Civil War. Forthal DN, Landucci G. The Killer Angels. In vitro reduction of virus infectivity by antibody-dependent cellmediated immunity. Constructing Essay. Journal of immunological methods. The Killer Angels. 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. Imperialism. 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 antibody-dependent cell-mediated cytotoxicity. Journal of immunological methods. The Killer. 2006; 308(1-2): 53-67. Migueles SA, Osborne CM, Royce C, Compton AA, Joshi RP, Weeks KA, et al. Lytic granule loading of CD8+ T cells is required for HIV-infected cell elimination associated with immune control. Immunity. 2008; 29(6): 1009-21. Vago L, Perna SK, Zanussi M, Mazzi B, Barlassina C, Stanghellini MT, et al. Loss of mismatched HLA in leukemia after stem-cell transplantation.

N Engl J Med. 2009; 361(5): 478- 88. Ziegner U, Campbell D, Weinhold K, Frank I, Rutstein R, Starr SE. Imperialism Causes. Deficient antibodydependent cellular cytotoxicity against human immunodeficiency virus (HIV)-expressing target cells in perinatal HIV infection. Clin Diagn Lab Immunol. The Killer Angels. 1999; 6(5): 718-24. T Lymphocytes Lymphocytes. Brunetta E, Fogli M, Varchetta S, Bozzo L, Hudspeth KL, Marcenaro E, et al. Angels. 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 natural resistance directed against MHC class I deficient tumor grafts. J Immunol. 1988; 140(2): 671-8. 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 edison prognostic predictors of HIV infection. J Clin Immunol. 2001; 21(3): 227-33. The Killer. Lambotte O, Ferrari G, Moog C, Yates NL, Liao HX, Parks RJ, et al. Heterogeneous neutralizing antibody and antibody-dependent cell cytotoxicity responses in HIV-1 elite controllers.

AIDS. Examples Of Sound. 2009; 23(8): 897-906. The Killer. Dalgleish A, Sinclair A, Steel M, Beatson D, Ludlam C, Habeshaw J. Imperialism Causes. Failure of ADCC to predict HIV-associated disease progression or outcome in a haemophiliac cohort. The Killer Angels. Clin Exp Immunol. And Reconstructing. 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. Angels. Antibody-secreting B cells in HIV infection. Curr Opin HIV AIDS. 2009; 4(5): 426-30.

Burke B, Barnett SW. Broadening our view of information, protective antibody responses against HIV. Current HIV research. 2007; 5(6): 625-41. Sattentau Q. Avoiding the void: cell-to-cell spread of human viruses.

Nat Rev Microbiol. 2008; 6(11): 815-26. Chamow SM, Zhang DZ, Tan XY, Mhatre SM, Marsters SA, Peers DH, et al. A humanized, bispecific immunoadhesin-antibody that retargets CD3+ effectors to kill HIV-1- infected cells. J Immunol. 1994; 153(9): 4268-80. The Killer Angels. Jolly C, Kashefi K, Hollinshead M, Sattentau QJ. HIV-1 cell to what were and consequences civil, 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 the killer, macrophages to what were the causes of the war, T cells across transient virological synapses. Blood. Angels. 2008; 111(9): 4660-3. Martin N, Welsch S, Jolly C, Briggs JA, Vaux D, Sattentau QJ. Examples. Virological synapsemediated spread of human immunodeficiency virus type 1 between T cells is sensitive to entry inhibition. J Virol. 2010; 84(7): 3516-27. Intellectual Support : My mentors Mark Connors and the killer 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 two distinctive perspectives in my graduate career, something most PhD scientist dont experience until their first post-doctoral experience.

While at NIH I will have received extensive support of staff from Richard Siegel, Director of the t lymphocytes vs b, NIH MD/PhD partnership program and the killer Michael Lenardo, Director the vs b, NIH/Oxford/Cambridge Scholars Program. The Killer Angels. While at on thomas edison, 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 the killer angels, FAES at NIH I have access to courses to improve lab specific skills and on thomas foundation knowledge. I have already participated a Vaccine Development course. At Oxford I will take seminars at angels, the Centre for Excellence in Teaching and Learning for training in war teaching skills.

I will also take courses pertinent to my research offered at the Dunn School of Pathology. Both the NIH and Oxford have libraries and the killer angels 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 lab. Safety In order to ensure our safety from vs b, hazardous blood samples we work under laminar flow hoods in a P2 facility with P3 practices. Samples We receive blood samples from angels, patients enrolled within our protocol. We also have access to 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 of sound devices its unique and the killer angels personal teaching style.

Within the University the Department of Pathology has an excellent reputation for graduate teaching, and has achieved 100% success in DPhil graduation within 4 years for the past 3 years. The Department has a strong graduate support structure, in which each student has a principal supervisor, the possibility of a cosupervisor, a departmental advisor, and a college advisor. The supervisor(s) will generally meet with the student multiple times a term, and t lymphocytes vs b lymphocytes each of the the killer, non-supervisory mentors will meet with the what civil war, candidate approximately once a term and will file reports on the candidates progress. The candidate will be expected to attend a series of high profile external seminars that take place once a week in the killer angels term time, and a regular series of internal seminars from leading and more junior University and Departmental investigators and students. Adjoa will attend and 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. Adjoa will also be encouraged to chat to other members of the department during tea lunch and coffee breaks, a longstanding Oxford institution! The Department has a fully equipped quiet library for literature research and other reading and writing. Adjoa will have her own writing up space close to her work bench, equipped with a portable computer and if required, an external screen.

Adjoa will have full access to Islands Essay, 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 the killer, biochemistry and chemistry departments and the Weatherall Institute of vs b lymphocytes, Molecular Medicine at the John Radcliffe Hospital for obtaining clinical samples and expertise. BD FACSAria IIu. BD Pathways 855. VICTOR Light luminescence plate reader. AutoMACS Pro Separator. AutoMACS Classic Separator.

Containment II/III Laboratory with 4 tissue culture hoods. Tissue culture. The Killer. The laboratory has a new tissue culture facility comprised of 8 double hoods and associated incubators and on thomas edison 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 the killer angels associated incubators and ancillary equipment, in which HIV-1 is grown and used to and Reconstructing, infect cells. Flow cytometry. Angels. The department has a core flow cytometry facility with three BD analyzers (2 x FACScalibur 2 x LSR2) and two sorters. Molecular biology. The Sattentau laboratory has all facilities for molecular biology carried out under containment levels I, -II and III. Light microscopy.

The department has 5 confocal microscopes of information edison, varying sophistication and resolution, two of angels, which are set up for live cell immunofluorescence work. The Galapagos Islands. 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 the killer 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. And Consequences Of The Civil. The department has two transmission electron microscopes and the killer angels a scanning electron microscope, all of and Reconstructing Essay, which are maintained and run as a central service facility by the killer, a skilled dedicated operator. Our collaborator in Oxford (Kay Grunewald) is located at the University Churchill campus, which is 4 miles from the Pathology Department. He maintains and uses 3 microscopes set up for cryo-tomography as follows.

300keV FEG cryo-electron microscope FEI TF30 Helium Polara with GIF2002 imaging filter (2 x 2k CCD) 300keV FEG cryo-electron microscope FEI TF30 with 4 x 4kCCD 120keV cryo-electron microscope FEI T12 with 4 x 4k CCD. Research Related Senior/Key Person Profile. [Our Web version of imperialism causes, this sample application can't reproduce the layout of the actual PDF forms. See below for the biographical sketch attachments.] My interest in the killer studying infectious diseases stems from the 2001 anthrax scare in the Washington D.C. area. I already had a strong interest in science but through my participation in the Gene Search Science Project at Catholic University the following summer I came to understand how medical research impacts treatment for routine illnesses and also plays a role in 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 the Gene Search Project and researched biochemical pathways that influence sickle cell anemia with Dr. William Winters at Howard University Hospital. And Reconstructing Essay. This experience taught me how research and medicine are intertwined and inspired me to become a physicianscientist. The Killer. At UMBC I was a member of the imperialism, Meyerhoff Scholars Program and 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. The Killer Angels. Not only did I learn about protein purification, gel electrophoresis, NMR, and ITC while studying MuLV RNA packaging, but more importantly of the time and discipline necessary for excellent research and edison the internal drive that keeps one focused. Working with Dr. Nikola Pavletich I learned the value of immediately organizing my data so that others could analyze my results quickly. In the angels, lab of Tom Cech I had the responsibility of designing a new protocol to study telomerase assembly, a skill that has enabled me to imperialism, design a novel assay to investigate AIDS specific questions in my graduate studies. The medical education Ive received at Columbia has given me a unique perspective with which I approach scientific questions. Under the angels, tutelage of Mark Connors and Quentin Sattentau, leaders in and Reconstructing their fields on nonprogressive HIV infection and viral transmission, my understanding of infectious disease and my capacity to pursue further research in angels these fields will be greatly enhanced. In addition, the courses, medical preceptorships, presentations, teaching, and career development activities I am undertaking in the forthcoming years make me an causes 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. The Killer Angels. Biochemistry.

44(10), 3735-3744. Miyazaki Y, Irobalieva RN, Tolbert BS, Smalls-Mantey A, Iyalla K, Loeliger K, D'Souza V, Khant H, Schmid MF, Garcia EL, Telesnitsky A, Chiu W, Summers MF. 2010. Structure of a conserved retroviral RNA packaging element by NMR spectroscopy and cryo-electron tomography. J Mol Biol.

404(5), 751-772. Smalls-Mantey A, Winter W. 2003. Biosynthesis of 2,3-diphosphoglycerate in Erythrocytes. What The Causes Of The Civil. 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 the killer angels, 2004 Annual Biomedical Research Conference for were the causes civil, Minority Students, November 2004. Smalls-Mantey A, Min J, Pavletich N. 2005. The Killer. Structural and Biochemical Studies of the Yeast Rad4-Rad23 Complex Bound to DNA. Poster presented at Tri-Institutional Gateways to the Laboratory Program Symposium and 2005 Leadership Alliance.

August 2005. Smalls-Mantey A, Miyazaki Y, Summers MF. 2007. Causes. 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. 2010. HIV-Specific Antibodies Mediate Rapid Antibody-Dependent Cellular Cytotoxicity Against Primary HIV-Infected CD4+ T Cells.

Poster presented at 2010 Keystone HIV Vaccines (X5) Meeting. March 2010. Smalls-Mantey A, Klein R, Doria-Rose N, Laub L, Rood J, Migueles S, Sattenatu. 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. Poster presented at 2010 NIH/Oxford/Cambridge Scholars Research Colloquium. Angels. 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 were civil, 2010 International AIDS Vaccine Conference. September 2010. Smalls-Mantey A. 2010. Antibody-Dependent Cellular Cytotoxicity and the Control of the killer, HIV. Talk given at information on thomas, Frontiers in Biomedicine NIH/Oxford/Cambridge Scholars Program student presentation series. November 2010. [Outside research support redacted from sample.] A. Personal Statement Regarding Project. Currently HIV-specific ADCC is considered one of the very top priorities in the killer angels the field of HIV-specific immunity. Our laboratory has assembled the best techniques and t lymphocytes reagents in the field to carry out this project.

We have extensive experience in HIV-specific antibodies and cytotoxicity. In addition we have a long track record of training students to prepare them for a carreer in biomedical research. 1985 - 1986 Intern in Pediatrics, The Boston Floating Hospital, New England Medical Center, Boston, Massachusetts 1986 - 1988 Resident in Pediatrics, The Boston Floating Hospital, New England Medical Center, Boston, Massachusetts 1988 1989 Chief Resident in Pediatrics, The Boston Floating Hospital, New England Medical Center, Boston, Massachusetts July 1989 - October 1989 Medical Staff Fellow, Respiratory Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD October 1989 - June 1993 U.S. Public Health Service, Research Associate (C.O.), Respiratory Viruses Section, Laboratory of angels, Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Islands, Health, Bethesda, MD July 1993 - June 1994 U.S. Public Health Service, Clinical Associate, Clinical Center, National Institute of Allergy and the killer angels Infectious Diseases, National Institutes of Health, Bethesda, MD January 1994 - June 1994 Clinical Fellow in Infectious Diseases, The Childrens Hospital of Philadelphia, Philadelphia, PA. June 1994 - December 2004 U.S.

Public Health Service, Medical Officer, National Institute of Allergy and Infectious Diseases, Clinical and The Galapagos Islands Essay Molecular Retrovirology Section, Laboratory of Immunoregulation, National Institutes of Health, Bethesda, MD December 2007- Present Chief, HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and the killer angels Infectious Diseases, National Institutes of Health, Bethesda, MD. Recent Honors and Editorial and 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 t lymphocytes vs b lymphocytes, 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 the killer highly associated with restriction of virus replication in a subgroup of The Galapagos Islands, HIV infected long term nonprogressors. PNAS 2000; 97(6): 2709-2714. Migueles SA, Laborico AC, Shupert WL, Sabbaghian MS, Rabin R, Hallahan C, Van Baarle D, Kostense S, Miedema F, McLaughlin M, Ehler L, Metcalf J, Liu S, and Connors M. HIV-specific CD8+ T cell proliferation is the killer angels coupled to perforin expression and information on thomas edison is maintained in nonprogressors. Nature Immunol 2002; 3(11); 1061-1068. Migueles SA, Laborico AC, Imamichi H, Shupert WL, Royce C, McLaughlin M, Ehler L, Metcalf J, Liu S, Hallahan CW, and Connors M. The differential ability of 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. Angels. 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 t lymphocytes vs b lymphocytes Connors M. Angels. Diminished proliferation of 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 The Galapagos Islands Connors M. Changes in angels paracrine IL-2 requirement, CCR7 expression, frequency, and cytokine secretion, of HIV-specific CD4+ T cells are a consequence of what the causes of the war, 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, OShea MA, Mican J, Packard B, Komoriya A, Palmer S, Wiegand AP, Maldarelli F, Coffin JM, Mellors JW, Hallahan CW, Follman DA and Connors M. Lytic Granule Loading of CD8+ T-Cells is Required for HIV-Infected Cell Elimination Associated with Immune Control. The Killer Angels. 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 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 information edison sera: clustering analysis and angels association with clinical variables. Essay. J Virol 2009 84(3): 1631-1636.

Doria-Rose NA and Connors M. Angels. Antibody-secreting B cells in HIV infection. Curr Opin HIV AIDS 2009 4:426-430 Wu X, Yang ZY, Li Y, Hogerkorp CM, Schief WR, Seaman MS, Zhou T, Schmidt SD, Wu L, Xu L, Longo NS, McKee K, O'Dell S, Louder MK, Wycuff DL, Feng Y, Nason M, Doria-Rose N, Connors M, Kwong PD, Roederer M, Wyatt RT, Nabel GJ and Mascola JR. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 2010 329:856-861. Migueles SA and Connors M. Long-term nonprogressive disease among untreated HIV-infected individuals: clinical implications of understanding immune control of HIV. JAMA 2010 304:194-201. [Redacted publication in press]

The research direction of the HIV-Specific Immunity Section of the t lymphocytes vs b, Laboratory of angels, Immunoregulation is focused upon and consequences of the war, mechanisms of the killer, immunity to HIV. The laboratory is staffed by PhD and MD scientists with extensive experience in the humoral or cellular immune response to HIV. What The Causes And Consequences Civil. In addition we have close collaborations with investigators at the killer, the NIAID Vaccine Research Center in what were the causes and consequences of the war the area of the killer, structure-function relationships of HIV-specific antibodies. Our laboratory is well equipped with multi-laser flow cytometers, automated magnetic sorters, and imaging equipment to carry out t lymphocytes vs b lymphocytes this project. Our laboratory is the killer angels supported by the research budget of the on thomas, Division of Intramural Research. Over the past 4 years we have received supplemental funding from the Intramural AIDS Targeted Antiretroviral Program (IATAP).

This will continue for the next 2 years. We have also received funding from the Office of AIDS Research for work on the killer angels 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 dImmunologie, Marseille, France 1999 - 2003 Reader, Section of Infectious Disease, Imperial College London, London UK 2003 - Professor of were the causes of the war, immunology, Department of Pathology, University of Oxford, Oxford UK. Other Experience and the killer Professional Memberships. 1995 - Member, American Association for The Galapagos Islands, 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 the killer angels, Vaccine Research Center (VRC) NIH Board of 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 information edison, HIV-1 Vaccine Discovery (U19) C. Selected Peer-Reviewed Publications. Most relevant to the killer, the current application. Martin N, Welsch S, Jolly C, Briggs JA, Vaux D and Sattentau QJ. (2010) Virological synapse-mediated spread of human immunodeficiency virus type-1 between T cells is sensitive to entry inhibition.

J. Virol. 84: 3516-3527. Gonzalez N, Bermejo M, Calonge E, Jolly C, Arenzana-Seisdedos F, Pablos JL, Sattentau QJ and Alcami J. (2010) SDF-1/CXCL12 production by mature dendritic cells inhibits the propagation of X4-tropic HIV-1 isolates at the dendritic cell-T-cell infectious synapse. J Virol. 84:4341-51 Groot F, Welsch S and Constructing and Reconstructing Essay Sattentau QJ. The Killer. (2008).

Efficient HIV-1 transmission from macrophages to devices, 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 angels, HIV-1 transmission. Nature Cell. Biol. 10: 211-219. Jolly C and Sattentau QJ (2007).

HIV-1 assembly, budding and cell-cell spread in T cells takes place in tetraspanin-enriched plasma membrane. J. Virol. Information. 81:7873-7884 Jolly C and Sattentau QJ (2007). Adhesion molecule interactions facilitate human immunodeficiency virus type-1-induced virological synapse formation between T cells. J. Virol.

81: 13916-13921. Jolly C, Mitar I and Sattentau QJ (2007). Angels. Requirement for Constructing and Reconstructing Essay, an intact actin and tubulin cytoskeleton for efficient HIV-1 assembly and spread. The Killer Angels. J. Virol. 81: 5547-6 Jolly C and Sattentau QJ. Essay. Human Immunodeficiency virus type-1 virological synapse formation in T cells requires lipid raft integrity.

J. Virol. Angels. 2005 79: 12088-12094. Jolly C, Kashefi K, Hollinshead M and Sattentau QJ (2004) HIV-1 cell-to-cell transfer across an information edison Env-induced, actin-dependent synapse. J. Exp Med. The Killer Angels. 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. J. Mol. On Thomas. 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. Angels. (2010). Potent adaptive immune responses induced against HIV-1 gp140 and influenza virus HA by a polyanionic carbomer. Examples Devices. Vaccine 28: 2482-2489.

Zanetti G, Briggs JAG, Grunewald K, Sattentau QJ and the killer Fuller SD. SIV spike glycoprotein structure in situ determined by cryo-electron tomography. What Were And Consequences War. Plos Pathogens August 2 (8): e83 Sheppard NC, Bates AC and Sattentau QJ (2007). A functional human IgM response to HIV-1 Env after immunization with NYVAC-HIV C. AIDS 19: 524-527. [Outside research support redacted from angels, sample.] PHS Fellowship Supplemental Form, Research Plan.

[Our Web version of this sample application can't reproduce the layout of the actual PDF forms. The attachments are included below. In the original version, these attachments met the page limits.] Understanding the basis of an immune response that controls infection or provides sterilizing immunity remains a major goal in the search for effective vaccines or immunotherapies for HIV. Antibodies (Abs) induced by Constructing, candidate vaccines to the surface envelope glycoprotein have not neutralized a broad array of primary virus isolates. For this reason, eliciting a cytotoxic cellular response has been the primary goal in most recent vaccine trials. However, this approach has not been successful in containing viral replication in vaccinees that have become HIV-infected. Antibody-dependant cellular cytotoxicity (ADCC) has been shown to mediate sterilizing immunity against challenge with pathogenic simian immunodeficiency virus [Hessel 2007]. In ADCC, Fc-bearing Abs bind viral epitopes coating an infected CD4+ target T cell and an Fc receptor bearing effector, most commonly natural killer cells (NKs), bind the Ab and use perforin to the killer, deliver granzymes which induce apoptosis in t lymphocytes the target. We want to angels, study ADCC in Islands Essay infected patients to angels, understand the magnitude and characteristics of the best responses achieved by natural infection.

First, we will compare ADCC mediated by the sera of t lymphocytes, a cohort of patients using a granzyme B cytotoxicity assay developed in our lab. Based on these findings, we will select the sera of patients with the most ADCC, generate monoclonal Abs (mAbs), and characterize the the killer angels, mAbs based on t lymphocytes vs b epitope specificity, affinity, potency, breadth, IgG isotype, and Fc type. We will also evaluate whether ADCC is the killer 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 lentiviral infection. We hypothesize that variations in ADCC activity of sera are dictated by the amount, specificity, and subclass of HIV-specific antibodies. Aim 1 : Characterize the potency of sera of HIV-infected individuals in ADCC. In ADCC, Abs bind viral epitopes that are presented by infected CD4+ T cells. The Galapagos Islands. NKs expressing an Fc receptor bind the Fc domain of the Ab and use perforin to deliver granzymes to the HIV-infected cell. Subsequently, granzymes induce apoptosis within the cell. Our lab has developed a flow cytometric assay that measures granzyme B delivered to an HIV-infected CD4+ target T cell. We will classify ADCC by the percent of target cells receiving granzyme and angels 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 t lymphocytes, progression and viral loads to angels, determine which contain Abs capable of mediating the highest levels of ADCC.

Compare the Constructing, ADCC and neutralizing activity of the killer angels, patient sera. Aim 2 : Characterize the specificity and breadth of causes, 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 angels, specific epitopes is required for ADCC. Define the were civil, breadth of the polyclonal sera by its ability to mediate ADCC in CD4+ T cells infected by different clades of the killer angels, HIV. Titer serum total IgG, IgG1, and IgG3 binding infected CD4+ T cells. Aim 3 : Characterize the structure and the causes and consequences war 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 the killer neutrophils) and infected target cells. Information Edison. We will specifically investigate: The structure of a functional ADCC synapse. The Killer. The kinetics of ADCC function in real time and examples of sound devices its relation to antibody type and the killer specificity. A role for antibody-dependent cell-mediated phagocytosis (ADCP) in elimination of HIV-infected cells. d. Receptors and effector molecules central to devices, 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 angels more public awareness about how to prevent HIV infection but with the vs b lymphocytes, growing incidence of HIV infection and the limitations of current antiretroviral therapy, there is an imperative need for a vaccine. One of the most critical areas of research on vaccines for HIV is the search for correlates of immunity. At present the only method for determining the potential benefits of a vaccine with regard to protection from infection or lowering of viral load upon the killer angels, infection remains very large clinical efficacy trials.

Determining correlates of immunity would tremendously accelerate the development process by permitting some estimation of clinical efficacy prior to a Phase III trial. Reliable correlates would permit screening of vaccine candidates at Constructing and Reconstructing, 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). The Killer. In addition to neutralization, antibodies (Abs) may fight viral infections by antibody-dependent cell-mediated phagocytosis (ADCP) or by antibody-dependent cellular cytotoxicity (ADCC). Constructing And Reconstructing Essay. 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 the killer bind the t lymphocytes, Fc? region of these Abs. Upon cross-linking of the Fc? receptor, NKs release perforin that punctures the targets cell membrane and deliver proteases such as granzyme B (GrB) which induce apoptosis. ADCC has become a major focus within the field following two important studies highlighting its potential importance in providing immunity to HIV. A recent study by Burton and colleagues demonstrated that neutralizing Abs with mutated Fc? receptor binding regions were less effective in protecting macaques from HIV whereas Abs with impaired complement binding conferred protection to macaques, suggesting that ADCC may be more important in the killer preventing infection than neutralization or complement activation alone 4. Prior to this study, it was widely accepted that infection of a single cell would lead to 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. In addition, some recent data in Essay human efficacy trials has also greatly increased interest in ADCC as an important component of vaccine induced immunity to the killer, HIV.

In September 2009 data from the phase III RV144 (Thai) vaccine trial were released and showed that the prime-boost combination of Constructing and Reconstructing, ALVACR HIV and AIDSVAXR B/E reduced HIV infection. This vaccine regimen was known to angels, not elicit a strong cellular or NAb response. It does, however, elicit binding antibodies that have suggested to Essay, the field that the the killer angels, 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 causes order to determine whether there were higher ADCC-mediating antibodies in uninfected vaccinees compared to the killer, those that were infected. Although HIV-specific ADCC is now considered an information extremely important part of vaccineinduced immunity several basic questions regarding the nature of an effective ADCC response have not been addressed. For example, the number, affinity, and specificities of the killer angels, antibodies necessary to causes, 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 the killer, individual antibodies that mediate HIV-specific ADCC. One of the initial goals of this project was to adapt our current killing assay to provide a more robust assay for HIV-specific ADCC. Constructing And Reconstructing Essay. Past studies of ADCC have been hampered by the availability of assays that are only angels partially quantitative. There are four primary methods that people use to measure ADCC 6. The most prevalent is the chromium release assays (CRA), which is highly variable, does not specifically account for the mechanism of killing, and is insufficiently quantitative 7. Constructing And Reconstructing. The ADCVI assay incubates targets, serum, and effectors for 24 hours and the supernatant is applied to the B95-8 cell line for the killer angels, 5-7 days. Causes. The endpoint is reduction of viral infection of the B95-8 cells 8. This method measures inhibition of viral production and subsequent infection but its disadvantages lie in the length of the assay and failure to measure killing of infected cells.

Another assay is the intracellular cytokine staining ADCC (ICS-ADCC) assay measures IFN-?, the primary cytokine responsible for the antiviral activity of many cells including NKs, CTLs, Th1, and the killer angels dendritic cells 9. The advantages of information, this assay are that multiple effector functions can be measured and all cells and Abs are from the same patient, but it is angels still a proxy that does not measure HIV-infected cell killing. The rapid and fluorometric antibody-dependent cellular cytotoxicity (RFADCC) assay directly measures cell killing but requires whole protein 10. While use of protein pulsed targets is a sensitive method, it likely places artificially high amounts of information on thomas, protein on the surface of infected cells, potentially overestimating the efficacy of ADCC. Recently our lab has developed a highly quantitative flow cytometric assay to measure GrB cytotoxicity using primary HIV-infected CD4+ T cells as targets and autologous NKs as effectors. This is an adaptation of an assay for measuring the cytotoxic activity of CTLs developed in the killer angels our lab11. This assay measures the cleavage of a GrB substrate, and what the causes and consequences of the civil war eliminates background cell death using a Live/Dead stain to produce accurate quantitative and highly reproducible results. In brief, CD4+ T cells are stimulated for 3 days and HIV infected. Autologous, negatively selected NKs are used as effectors. Effectors and targets are labeled with surface dyes so that they can be discriminated.

NKs, targets and angels serum are incubated in the presence of Islands Essay, a granzyme cleavable fluorescent substrate. Granzyme delivery to the killer angels, the target cell and elimination of HIV-infected targets can then be measured by flow cytometry (Figure 1). Cellular GrB content. GrB cleaves GranToxiLux substrate (FITC), indicating the amount of GrB present within a target cell (Pacific Blue). Elimination of HIVSF162-infected cells. The Galapagos Islands Essay. Live targets are stained for intracellular HIV capsid, p24 (PE). Some infected cells show downregulation of CD4 (PE-Cy7). A reduction in the number of p24 stained cells is the killer represented as Infected Cell Elimination (ICE) and is an indication of cell death. In the example above, ICEInfected+Effectors+Serum = [(58.2-25.8)/58.2] x 100 = 54.9%. There are several advantages to this assay over older assays that use mismatched cell lines.

Because NKs lyse target cells in the context of lymphocytes, MHC mismatch and cause nonspecific killing, autologous cells are used in our assay to reduce background. The Killer. 12. In addition, because NK function is diminished in HIV-infected patients, we use the NK cells and CD4+ T cell targets from uninfected patients in our assay as a readout for the effectiveness of a given serum sample in mediating ADCC 13, 14. Lymphocytes. We observed variations in NKs from normal individuals in their ability to mediate ADCC and choose donors that provide optimal signal to noise ratio that we will use to compare the the killer, 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 examples devices, antigen pulsed cell lines.

Other advantages include our assays ability to measure the mechanism of ADCC (granzyme delivery) and the outcome (death of infected cells) (Figure 2). MHC-1 is the killer down-regulated in lymphocytes 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 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 a dose dependent manner, and angels (3) GrB delivery is proportional to cell death. Aim 1: Characterize the magnitude of ADCC in what were the causes and consequences of the war HIV infected individuals . Rational : There is considerable controversy regarding the magnitude of ADCC activity in sera from HIV+ individuals and how it correlates with disease progression.

It has been suggested that sera from elite controllers exhibit greater ADCC activity which correlates with CD4+ T cell count 17, 18 while others have sighted no correlation between ADCC and disease progression 19, 20.We will compare the serum of HIV+ individuals with various rates of progression and viral loads to determine which contain Abs capable of mediating the highest levels of ADCC. We will also compare the ADCC and angels neutralizing activity of patient serum to were, evaluate whether or not ADCC and neutralization always occur together in polyclonal sera which is yet to be determined 21, 22. Methods : Over the past several years, in collaboration with the Vaccine Research Center (VRC) our laboratory has focused upon recruiting HIV-infected patients with broadly crossneutralizing antibodies. Angels. We have extensive clinical data and neutralization data for all of the patients. With the t lymphocytes, data we generate from our ADCC assay we are able to compare multiple indicators of immunity with ADCC. Expected Outcomes/Interpretation : Based on in vitro and passive transfer macaque studies, we expect LTNPs to exhibit greater ADCC than progressors. Our current knowledge attributes LTNP delayed progression to superior CTL cytotoxicity but our data may show ADCC also to the killer angels, be a significant factor 11. Potential Complications : We do not foresee any difficulties in t lymphocytes accomplishing this objective.

Aim 2: Characterize MAb from serum identified as having potent ADCC activity with regard to the killer angels, specificity. Rational/Methods : HIV-infected cells express Envelope (Env) protein on imperialism their surface which is recognized by NAbs and angels presumably by ADCC-mediating Abs. We will use standard Nabs (including b12, 2F5, 2G12, 447-52D, 17B, and VRC01) and patient derived MAbs to information, probe specificities required for ADCC. An ideal HIV vaccine would be able to protect against diverse virus strains so it is angels important to determine whether Abs raised against one clade of virus would be able to mediate ADCC in of sound devices CD4+ T cells infected by different clades. Angels. 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 t lymphocytes, clade B HIV+ patients. The Killer. IgG1 and IgG3 are the predominant IgG isotypes with roles in ADCC. It is possible that variations in t lymphocytes 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 angels measure total bound IgG, IgG1, and IgG3 by vs b lymphocytes, flow cytometry.

We believe flow cytometry is the killer a better way of measuring titers of binding Abs as compared to ELISA because Abs will recognize all possible epitopes on imperialism 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 the killer, subclass binding and information 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 the killer will relate structure to function.

Multiple mechanisms for cell-to-cell spread of t lymphocytes vs b, 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 the killer angels, investigate ADCC in t lymphocytes lymphocytes HIV using NKs or macrophages as effectors and CD4+ T cells as targets. In 1994 one group designed a bispecific antibody with anti-CD4 and anti CD3 heavy chains that would redirect CD8+ T cells to kill HIV infected targets 24. With fluorescent microscopy they observed after 1 hour of incubation that 24% targets had formed conjugates with CD8+ T cells although many more cells had lysed. The Killer Angels. At 2 hours 50 - 80% of targets were conjugated and undergoing lysis and by imperialism causes, 24 hours all targets had been lysed. The Killer. However, the bispecific antibody may not be representative of were the causes and consequences civil war, ADCC with naturally occurring HIV-specific antibodies. In addition, the structure of the NK to HIV-infected target synapse was not examined. Methods : The lab of Quentin Sattentau has focused on the killer angels examining the synapse of cells involved in information on thomas edison HIV infection.

They were the first to demonstrate HIV-1 spread between T cells via virological synapses and nanotube structures for viral transmission between CD4+ T cells 25. Angels. They have recently demonstrated that macrophages can infect CD4+ T cells every 6 hours and that cell-tocell transfer of and Reconstructing Essay, 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). Cell populations will be negatively selected from PBMCs using magnetic cell sorting. HIV-infected CD4+ T cells will be mixed with patient serum or Abs of multiple specificities (see Aim 2) and the killer NKs to evaluate ADCC; or neutrophils/monocytes to edison, evaluate antibody-dependent cell-mediated phagocytosis (ADCP) and applied to angels, poly-L-lysine coated cover slips. Cover slips will be fixed in paraformaldehyde, quenched with NH4Cl, permeabilized with Triton-X, and t lymphocytes lymphocytes 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 the killer tomography (TEM) to information edison, generate higher resolution static images of the ADCC functional synapse. For TEM targets, serum, and effectors will be incubated for approximately 1 hour, fixed in paraformaldehyde and glutaraldehyde, and stained with osmium tetroxide. Samples will be embedded in epoxy resin, cut, and the killer imaged using a 300kV FEI Technai TF30 27.

If necessary cryo-EM will also be used for structural studies with the aid of of sound devices, Oxford collaborator Kay Grunewald. These experiments will be completed using the pathology departments core bioimaging facility and I will take departments Advanced Light Microscopy and Electron Microscopy course in preparation for this research. Expected Outcomes : We expect to elucidate the angels, kinetic and The Galapagos Islands Essay functional relationship between ADCC components and answer questions such as what density of Env epitopes are needed to recruit effectors, how many effectors are recruited per target. We do not foresee any difficulties in accomplishing this objective. The results of these studies will include novel MAb with possible therapeutic value; a new tool for the study of ADCC with potential utility for HIV vaccine trials; and the killer angels increased understanding of basic HIV immunology. Were. In the wake of the the killer, 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 what the causes of the war, 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 the killer 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 were civil, Intramural Research policies.

Phlebotomy may cause some discomfort, and the killer angels occasionally some bleeding or bruising at imperialism, the site. On rare occasions, people faint while having blood drawn. Blood drawing will not exceed 150 milliliters (30 teaspoonfuls) on the killer angels any day or visit. In the course of any time frame during this study, the total amount of blood will not exceed 10.5mL/kg, or 550 milliliters over any 8-week period, which is within the safety guidelines for blood drawing practiced at what were and consequences war, the Clinical Center. Like standard phlebotomy, leukapheresis is occasionally associated with local bleeding and the killer angels 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 can usually be relieved by information edison, chewing a calcium-rich tablet that the staff will provide. In addition, on very rare occasions (less than 1 in every 1,000 times), malfunction of the leukapheresis machine can result in blood loss of up to 450 milliliters. Trained medical personnel who are equipped to the killer angels, deal with any of these potential problems will always be on imperialism hand during the angels, procedure. Inclusion of Women and Minorities. Gender, Ethnicity and information on thomas 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 the killer angels, gender, race or ethnicity from the information on thomas, pool of patients that receive care in Clinics 8 at the NIH Clinical Center. The Killer Angels. Patients will be recruited from outside the NIH community by imperialism causes, advertisements posted in the Clinical Center, the 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 angels, the study as to the potential risks of and Reconstructing, discontinuing HAART therapy and the potential benefits of continuing HAART therapy, in the setting of the killer, a documented virologic and/or immunologic response. Patients who do not fully comprehend these potential risks of HAART cessation, in the opinion of the study team, will not be offered participation in the study. Patients stopping HAART therapy will be monitored closely for virologic and immunologic relapse and will be offered therapy, based upon The Galapagos Islands, the algorithm for safety outlined above. Target enrollment for this study is 300 individuals and is currently ongoing. Inclusion of Children (and Pregnant Women) Inclusion of the killer angels, Children and what were of the civil Pregnant Women. This study will be confined to HIV-infected adults greater than or equal to 18 years of age. As an the killer observational study there is no therapeutic benefit or clinical intervention resulting from participation in this trial, thereby children are not being denied the potential benefits of a research intervention. Constructing And Reconstructing. We also do not have the historical research database and in vitro findings on HLA linkages with LTNP in the killer angels the pediatric population to make valid comparisons within that cohort.

The potential risks of imperialism, withdrawing therapy in minors have not been studied and therefore may present unknown additional risks to that study population. The Killer Angels. Comparable units specializing in pediatric HIV are available at were the causes of the civil, the NIH to the killer, 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 this study. Any woman of childbearing potential must have a negative pregnancy test within two weeks prior to study entry. All participants who engage in heterosexual intercourse must use two forms of reliable birth control for the duration of the study. When I entered the NIH/Oxford/Cambridge Scholars program I identified Mark Connors and Quentin Sattentau as two HIV researchers with whom I would like to train with because of their focus on HIV immunology, vaccine design, and their expertise in basic immunology techniques, flow cytometry, and microscopy. I initiated contact between the two individuals and they agreed to start a collaborative project with me. After studying NAbs with Mark Connors for one summer I decided I wanted to causes, focus on antibodies that mediate ADCC. I outlined the facets of ADCC I wanted to investigate then received feedback from both mentors. I subsequently wrote the the killer, proposal that was edited by both mentors and Mark Connors made final revisions.

I meet multiple times during the week with Dr. Connors to discuss my research progress and to plan future experiments. Essay. We also conduct quarterly phone conferences with Dr. Sattentau, maintain a regular email correspondence, and meet at conferences. Communication will continue in the killer the same manner while I am in Quentin Sattentaus lab. Selection of Sponsors and Institution. Selection of Institution. I decided to join Columbias MSTP program because of its tradition of exemplary medical education, medical research, and Constructing and Reconstructing unparalleled support offered to students from program administrators. Because of my previous research experience with HIV I knew I wanted to continue research in this field.

I decided to join the NIH/Oxford/ Cambridge Scholars Program to complete my dissertation research because it would provide me access to the killer, a more extensive network of The Galapagos Islands Essay, scientists than Columbia could. Oxford has a particularly strong network of HIV investigators and the structure of its graduate program allows for the killer angels, a particularly specialized education. As a graduate student in the pathology department I am allowed to select seminars and accelerated 1-day to 1-week courses that allow me to attain skills quickly and immediately implement them into my research. In addition, the 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 NIHs Foundation for Advanced Education in the Sciences Ive had the opportunity to take courses that will help me towards my goal as in what the causes and consequences of the civil war infectious disease investigator such as the Vaccine Development course I completed. The NIH/Oxford/Cambridge Scholars Program is the killer designed so that students work with a mentor at NIH and one at a university. On Thomas. When I joined the program I searched for angels, HIV investigators throughout NIH and the causes Oxford and identified Mark Connors and Quentin Sattentau as potential mentors because I wanted to conduct research that had direct implications in vaccine development.

Quentin Sattentau was studying how to elicit effective anti-HIV neutralizing Abs (NAbs) for vaccines and adjuvants to the killer angels, 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. Connorss expertise in NAbs of long-term nonprogressors (LTNPs) would complement Dr. Sattentaus vaccine development goals. In addition, Dr. T Lymphocytes Vs B Lymphocytes. Connorss unique cohort of LTNPs would provide ready access to samples to study many facets of HIV infection. The Killer. Finally, I believe Dr. Sattentaus approach to research as a PhD and Dr.

Connors as an Islands 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 the killer angels NOT-OD-10- 019. As an undergraduate at UMBC I took a semester-long course entitled Ethics/Integrity in Scientific Research which first help me to understand the responsibility scientists have to what and consequences of the civil, one another and the killer angels medical community honestly share information. As a Columbia medical student, I have taken the Hippocratic Oath to guide my patient care and I am expected to 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 Research Ethics.

Since I will have access to sensitive patient data it is essential that I maintain the confidentiality of t lymphocytes vs b lymphocytes, these individuals. When I started research at NIH I participated in a patient confidentiality seminar. Oxford offers an Ethics: Confidentiality course in which I will enroll to better my further my understanding and ability to maintain ethical practices with regards to the killer angels, research. As a physician, I hope to what were and consequences of the civil war, alleviate an individuals immediate suffering; and as a scientist I hope to contribute to long-term solutions that can prevent suffering. The Killer. To work most effectively at the interface of medicine and science, I have endeavored to The Galapagos Essay, earn an MD/PhD.

I believe that the combined degrees greatest value lies in the killer the perspective that it affords: to the causes and consequences, approach patient care with a researchers eye, and to approach research with a physicians focus on the killer improving the quality of life. A few years ago I conducted research on telomerase, an Essay enzyme that maintains healthy chromosome length. When telomerase is upregulated, as it is in 90% of the killer, carcinomas, cells can propagate indefinitely. 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 examples measuring their growth rates, I noticed two things. The first was that cells with low levels of telomerase grew slowly. Secondly, these cells had abnormal morphologies, as do tumor cells. These observations led me to wonder whether the progression of cancer in individuals with DC was slower than in patients without it because DC patients have less active telomerase.

Upon discussing this with my P.I., he acknowledged having never considered his research from that aspect. A literature search demonstrated a lack of any substantial research concerning this question. Research in the killer biochemistry affords many new advances in medicine, but through that experience the importance of keeping a broader medical picture in mind became clear to me. My goals as a physician scientist are to treat patients and conduct research that will allow me to impact patients I will never meet through therapeutic discovery; specifically serving as a creative link between science and medicine in and consequences of the the field of infectious disease. The training I will receive in Oxfords doctorate program will prepare me to be a competitive investigator through a tailored curriculum, expert dual-mentoring, learning to work in a collaborative environment, and by giving me extensive writing experience via paper submissions and even through this grant. Angels. 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 t lymphocytes understanding that I want to the killer angels, be a physician-scientist has given me the opportunity to imperialism, carefully cultivate these skills early in angels my career. Activities Planned Under This Award.

Research 80%, Seminars/Courses 10%, Presentation/Career Development/Clinical 10% Research Skills : While working in Mark Connorss 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 causes, 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 program I took a grant-writing workshop sponsored by the NIH Graduate Partnership Program. The Killer. I also completed a 3-day grant-writing course during my senior year of college. Islands Essay. I will improve my writing skills through preparation of manuscripts based on my research to be submitted for publication, applying for training grants, and submission of a report for the killer angels, my transfer viva (qualifying exam). I will also complete the Scientific Writing from The Galapagos, a Readers Perspective seminar. Discipline specific learning : I completed the 3-day Vaccines: Development and Evaluation of Efficacy course offered by FAES in February 2010. I also attended Psychiatry and HIV, a 2-day workshop offered by the American Psychiatric Association so I could learn to effectively interact with HIV+ patients I encounter.

I attend weekly seminar series hosted at the NIH such as the Wednesday Afternoon Lecture Series, Immunology Interest Group seminar series, and weekly lab meetings. Bench to bedside clinical training : I will attend the Clinical Research Training Program (CRTP) weekly rounds. I will also have the angels, opportunity to be mentored by an infectious disease clinician. Presentations : I will continue to annually attend and present at pertinent Keystone Symposia and the Annual AIDS Vaccine conference. I have also had opportunities to present posters at the NIH/Oxford Cambridge Scholars Program Colloquium and the Oxford Pathology Graduate Student Symposium. I have given a talk to my graduate program journal club and will have more opportunities to present my research in lab meetings. Career Development : The NIH/Oxford/Cambridge Scholars programs hosts a seminar series where leaders in government/academic research, the pharmaceutical industry, and finance speak with us about their career. I also attended NIAID Fellows retreat that focused on career development.

Teaching : As I prepare to t lymphocytes lymphocytes, 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 Sattentaus lab I will learn to apply microscopic imaging to studying HIV infection. I will have weekly meetings to discuss my research progress. We will have phone conferences and meet with Dr. Connors at various conferences throughout the angels, year. I have also been assigned a graduate advisor within the pathology department but not in what and consequences civil war 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. The Killer Angels. I will complete the following 1-day courses offered at Oxford: Writing Skills Paper and Thesis; Doctoral Thesis Writing,

Discipline specific learning : I will participate in courses and Skills Workshops offered by Oxford including Advanced Light Microscopy, Electron Microscopy, and Introduction to vs b lymphocytes, Statistics. Bench to the killer, bedside clinical training : I will attend the what and consequences of the civil, Nuffield Department of Clinical Medicine Grand Rounds and shadow an infectious disease clinician. Career Development : See above. I will also attend the the killer, 4-day Oxford GRADschool, a personal development course. Teaching : I will seek to be an undergraduate lab instructor and take the information, Oxford course Teaching and Learning Skills to prepare myself.

Year 3 and Year 4: Medical School (Columbia) In the summer after 11th grade I participated in the intensive 6-week Gene Search Program at the Catholic University of America that introduced me to molecular biology and the killer the exciting race to sequence the human genome. That summer, I learned much more than how to Constructing, run a gel; I learned to angels, read and examples of sound devices comprehend primary research articles and how to design experiments. The Killer Angels. Because of my accomplishments that summer, I was invited to participate in an extension of the Gene Search Program during my 12th grade year. Essay. This program inspired me to pursue a career in biomedical research because I began to understand how the principles I was learning in school fostered scientific discovery. As a high school senior, I worked with Dr. William Winter at Howard University School of Medicine to investigate pathways that regulate 2,3-diphosphoglycerate (2,3-DPG) levels in red blood cells (RBC). 2,3-DPG lowers the affinity of hemoglobin for oxygen, thereby facilitating oxygen release to tissues. Patients suffering with sickle cell anemia have high levels of 2,3- DPG.

While this effect may seem advantageous to patients with sickle cell anemia, deoxygenating hemoglobin ultimately causes red blood cells to sickle by promoting hemoglobin polymerization. The Killer. 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 and consequences, using spectrophotometry to measure a by-product of the 2,3-DPG pathway. An exciting therapeutic prospect of our research is that an antagonist of the the killer, A3 receptor may prevent the accumulation of on thomas edison, 2,3-DPG and RBC sickling in patients with sickle cell anemia. The Killer. I documented this work in a five-chapter thesis, in accordance with my high schools Science and Technology Program, and presented it at my schools science fair, where I was awarded third place in biochemistry. During college I spent four years working with Dr. Michael Summers to edison, investigate Moloney Murine Leukemia Virus (MuLV) dimerization. Understanding dimerization is key to developing gene and antiviral therapies.

MuLV is similar to HIV in that it is a retrovirus that packages two copies of the killer angels, its RNA genome. What Were Of The Civil. 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. The Killer. Previous work in the causes and consequences the Summers lab suggested a riboswitch mechanism for the killer angels, MLV genome packaging, where, in monomeric RNA, Psi-site UCUG segments capable of and Reconstructing, binding NC are sequestered by base pairing, but upon dimerization, become exposed to bind NC. My project was to investigate whether similar sequences in the Psi-site could also bind NC. Using isothermal titration calorimetry and angels nuclear magnetic resonance, we identified short RNAs (ACAG, UUUG, and UCCG) that bind NC with nanomolar affinity. Our findings suggest that: 1) binding depends on an unpaired guanosine, 2) binding is enhanced in short RNAs containing terminal phosphates, and 3) binding affinity varies by more than one order of magnitude depending on Islands Essay which three nucleotides lie upstream of the guanosine. The Killer. The paper I co-authored (Dey, A., et. Causes. al., 2005) extends an established model for genome recognition, in which the NC domains of the killer angels, assembling Gag molecules interact with multiple X(i-3)-X(i-2)-X(i-1)-G(i) elements (X is a variable nucleotide) that appear to be preferentially exposed in the dimeric RNA. I presented this research at information on thomas, the 2004 ABRCMS and at multiple UMBC symposiums. I continued to the killer, 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 and Reconstructing, 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. The Killer. Nikola Pavletich toward solving the crystal structure of the Saccharomyces cerevisiae Rad4-Rad23 complex bound to a DNA substrate. Of Sound. Rad4-Rad23 is a homolog of the killer, human XPC-HR23B, a DNA damage-repair protein. In its mutated form, XPC-HR23B causes the imperialism, disease Xeroderma Pigmentosum. Patients are extremely sensitive to UV-light and develop skin cancer during childhood.

I identified DNA substrates to be used in crystallization trials by angels, HPLC-purifying DNA, performing gel-shift assays, and setting up crystal trays. I presented this work in a talk before the vs b, Tri-Institutional community and during posters sessions at the 2005 Leadership Alliance National Conference and at the 2005 SACNAS National Conference. In 2006 I studied telomerase assembly in the lab of Dr. Thomas Cech at the University of Colorado at Boulder. The central role telomerase plays in protecting chromosome integrity places telomerase at the heart of two common human ailmentscancer and aging. The Killer. To study how and where in the cell telomerase is vs b assembled from its RNA and protein components, we used the angels, 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 Essay that a polyadenylated precursor form of TLC1 is exported to the cytoplasm where it associates with Sm proteins.

Mtr10p then plays a role in the killer importing the TLC1-Sm complex back into the nucleus, where the telomerase holoenzyme is assembled. Using cellular fractionation and real-time RT-PCR, we attempted to localize TLC1 in its various stages. During the summer between my first and second year of medical school I joined the lab of Mark Connors where I screened patient sera for breadth and potency of examples of sound devices, neutralizing Abs against HIV using a TZMBL neutralization assay. We demonstrated that that progressor serum has greater breadth in potency in neutralizing HIV than Long-Term Nonprogressors (Doria- Rose, N., et al., 2009). Studying NAbs peaked my interested in other anti-viral mechanisms mediated Abs and lead to my proposed project of investigating antibody-dependent cellular cytotoxicity. Each research experience has shown me the many nuances of a research career. I learned about: 1) the the killer angels, importance of edison, basic research in developing medicines, 2) the time, organization, and ingenuity it takes to angels, conduct research, and 3) the what the causes and consequences war, vital role that a physician-scientist plays in translating basic research into angels, medical treatment. Constructing And Reconstructing Essay. Although Ive experienced frustrations and the killer 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 t lymphocytes vs b, sample.] QUENTIN SATTENTAU MENTOR STATEMENT. [Redacted from sample.] [Our Web version of this sample application can't reproduce the layout of the actual summary statement. See below for the killer angels, the data fields and critiques.] Center for Scientific Review Special Emphasis Panel.

Fellowships: AIDS Predoctoral and imperialism Postdoctoral. RESUME AND SUMMARY OF DISCUSSION: In this application, the fellowship candidate proposes to investigate antibody-dependent cellular cytotoxicity (ADCC) in HIV-infected patients do determine the extent of protection that ADCC provides. The reviewers noted that the candidate is outstanding, with a strong record of research training and accomplishment. The candidate appears to the killer angels, be highly motivated. Her sponsors, at both institutions, are well qualified to devices, 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 two sites, and the failure to address pitfalls and alternatives of the research project. These weaknesses, however, did not detract from the reviewers enthusiasm. This training project will have a high impact in the killer ensuring that the t lymphocytes vs b, candidate maintains her potential to become an angels independent clinical researcher. DESCRIPTION (provided by applicant): Understanding the basis of an immune response that controls infection or provides sterilizing immunity remains a major goal in the search for effective vaccines or immunotherapies for HIV.

Antibodies (Abs) induced by candidate vaccines to the surface envelope glycoprotein have not neutralized a broad array of primary virus isolates. For this reason, eliciting a cytotoxic cellular response has been the Constructing and Reconstructing Essay, primary goal in most recent vaccine trials. However, this approach has not been successful in containing viral replication in the killer angels vaccinees that have become HIV-infected. Antibody-dependant cellular cytotoxicity (ADCC) has been shown to information edison, 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 killer the target.

We want to study ADCC in infected patients to understand the magnitude and characteristics of the best responses achieved by Constructing and Reconstructing, natural infection. First, we will compare ADCC mediated by the sera of the killer angels, a cohort of patients using a granzyme B cytotoxicity assay developed in t lymphocytes lymphocytes our lab. Based on these findings, we will select the angels, 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 t lymphocytes lymphocytes 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 lentiviral infection. We hypothesize that variations in ADCC activity of sera are dictated by the amount, specificity, and subclass of HIV-specific antibodies. Angels. Aim 1: Characterize the potency of sera of HIV-infected individuals in ADCC. The Galapagos Essay. Aim 2: Characterize the specificity and breadth of antibodies with ADCC activity. Aim 3: Characterize the structure and function of the angels, 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 on thomas tomography. Understanding the role of antibody-dependent cellular cytotoxicity (ADCC) in the killer angels HIV could provide important insights for examples of sound, induction of angels, this activity through vaccination. This project seeks to imperialism, characterize the Abs that mediate ADCC and image the the killer angels, functional synapse formed by Constructing Essay, cellular components involved in ADCC with the goal of defining new goals for the development of HIV vaccines and therapeutics. Fellowship Applicant: 1.

Sponsors, Collaborators, and Consultants: 1. Research Training Plan: 2. Training Potential: 1. Institutional Environment Commitment to Training: 2. Overall Impact/Merit : This proposal is from an applicant who is currently enrolled in the NIH M.D./Ph.D. Angels. Partnership Training Program and 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 Oxford University and complete her medical training at Columbia University. The applicant is highly recommended by previous research mentors and has an t lymphocytes outstanding academic record. Her research experience, which includes four years of undergraduate research, is angels 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 imperialism causes, expertise and interests of the mentor, focuses on the killer angels relationships between antibody-dependent cellular cytotoxicity (ADCC) in HIV-1-infected patients, HIV-1-associated disease progression, and antibody subtype. Additional experiments, which will draw on the expertise of the co-sponsor, will investigate the target-effector synapse during ADCC.

These studies will be significant for Essay, their basic science and translational value. The Killer Angels. The training plan is unique in that training and were the causes and consequences of the war research will be accomplished in two separate laboratories of the sponsor and co-sponsor. Angels. This proposal outlines an excellent training opportunity that will greatly benefit the applicant and her potential for establishing an edison 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 the killer very inquisitive. Her undergraduate research mentor characterized her as easily among the top two or three of the Islands Essay, more than 200 current and the killer angels former undergraduates that he has mentored. The applicant has four years of undergraduate research experience, which involved work with the Moloney Murine Leukemia Virus, and what the causes of the war research performed during a summer program at the Howard Hughes Medical Institute focused on studies of telomerase.

Technical approaches for the killer, 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 applicant has been included as a contributing author on 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 imperialism numerous awards and recognitions reflecting superior academic performance. The collaborative project outlined in the proposal was an outgrowth of a dialog initiated by the killer, the applicant between the information edison, 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 applicants mentor and angels sponsor, who is currently Chief of the HIV-Specific Immunity Section in the Laboratory of Immunoregulation, NIAID/NIH, is an established and productive senior investigator with research support provided by the NIH. The co-sponsor is also a productive researcher with a consistent record of examples of sound devices, support for studies related to angels, HIV/AIDS. The research interests and expertise of the sponsor and co-sponsor will provide excellent support for the applicants research and training.

The expertise of the Islands Essay, co-sponsor will be particularly relevant to studies outlined in Aim 3. The sponsor has trained an average of four students per year over 20 years, suggesting an excellent training environment for the applicant. Similarly, the co-sponsor has trained nine Ph.D. trainees since 2003. The Killer. During her predoctoral fellowship, the causes, applicant will be interacting with four post-baccalaureate students and one M.D. in the sponsors lab, and four Ph.D. The Killer Angels. trainees in the co-sponsors laboratory. The latter trainees will overlap with the applicant for one year or more. These interactions will enrich the applicants training. The research plan is built on studies of antibody-dependent cellular cytotoxicity in HIV-1-infected individuals. Experiments will examine the The Galapagos Islands, potency of sera of angels, HIV-1-infected individuals in imperialism causes ADCC (Aim 1), the specificity and breadth of antibodies with ADCC activity (Aim 2), and the structure/function of the the killer, target-effector synapse that mediates ADCC.

The central feature of the proposed research is a novel and quantitative ADCC assay (developed in the sponsors lab) that offers significant improvements over The Galapagos other ADCC assays. The Killer. 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 The Galapagos Islands Essay sponsors are well positioned to perform these studies, since the patient populations and angels study procedures are already in place. The applicant is The Galapagos Islands participating in the NIH/Oxford/Cambridge Scholars Program, which promotes research with a mentor at the NIH and angels another mentor at a university. Consistent with the the causes and consequences civil, Scholars Program, the the killer, research training plan includes studies and training in year 1 in the sponsors lab at the NIH, continued studies and training in year 2 in the co-sponsors lab at Oxford, and years 3 and 4 in of sound devices 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 the killer angels opportunities for presentation of results and teaching. Training at t lymphocytes vs b, the NIH (sponsor) will be a continuation of the current laboratory work, with increased emphasis on independent research and the killer angels critical thinking. Training at Oxford (co-sponsor) will include skills development in experiments involving infectious HIV-1, microscopic imaging, and biochemical and serological techniques (such as ELISA, gel electrophoresis, and mass spectrometry). Although the targeted patient enrollment is t lymphocytes given as 300 HIV-1-infected individuals, the experimental plan does not provide details regarding the scope of studies in Aim 1. Correlates of the killer angels, ADCC to be studied in Aim 1 (rates of progression and viral loads) were not described in sufficient detail. How will rates of progression be measured? Will viral load be documented on 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 the causes and consequences of the civil war acquired expertise, and enhance the capability of the the killer angels, applicant to develop an Islands Essay independent and productive research career. 5. Institutional Environment Commitment to Training: The resources and facilities at both institutions will provide outstanding environments for training and research. A more detailed plan regarding the coordination of training plans between the sponsor and co-sponsor would be valuable, considering the distance and the killer angels time difference between the Constructing Essay, two performance sites. Training in the Responsible Conduct of Research:

Comments on Format (Required): The description of RCR training is brief and does not provide a detailed plan for formal training. However, enrollment in two formal courses at Oxford (both focused on ethics) is mentioned. Comments on Subject Matter (Required): Training courses and certifications at the NIH and angels Oxford should provide information on relevant subjects. Comments on Faculty Participation (Required): Faculty participation could not be evaluated from the description of RCR training. Comments on Duration (Required): The duration appears to be adequate, although exact contact hours were not provided.

Comments on Frequency (Required): The frequency of Constructing and Reconstructing Essay, training could not be discerned from the the killer angels, description of RCR training. Fellowship Applicant: 2. Sponsors, Collaborators, and Consultants: 1. Research Training Plan: 2. Training Potential: 2. Institutional Environment Commitment to Training: 1.

Overall Impact/Merit : This is an outstanding proposal from a highly qualified applicant. The applicant has an exemplary scholastic record, strong research history and outstanding letters of reference although she lacks a first author publication. The applicant has chosen two superb sponsors with complementary skill sets. In fact, the applicant brought these two investigators together herself. Both sponsors have excellent training track records and 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 an HIV infected cells. Using this novel assay the applicant plans to compare ADCC in HIV+ subjects with various rates of causes, disease progression and to define the 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. Sattentau. This aim will use fixed and live cell laser scanning confocal microscopy and TEM to the killer, examine the samples between NK and other cells with ADCC activity. If the Essay, applicant is successful the data from the killer angels, this project will be highly important for HIV vaccine development. The research project however is quite ambitious and The Galapagos Essay no timeline is given. It appears that the applicant plan to spend 1 more year in the Dr. Connors lab and 1 year in the killer Dr. Vs B. Sattentau lab making it a very busy two years if the applicant plans to finish all the the killer angels, work they outlined. Despite the highly ambitious nature of the proposed research project the examples devices, overall project goals warrant further study and the applicant herself is of the highest caliber making this application worthy of funding. The applicant has a very strong research background dating back to high school where she participated in the Gene Search Project at Howard University Hospital.

As an angels undergraduate at UMBC she was a member of the of sound devices, Meyerhoff Scholars Program funded by the HHMI. The applicant has coauthored 2 papers and the killer angels is the lymphocytes, first author on 8 posters and 1 oral presentation. The applicant has extremely strong letters of the killer angels, recommendations, one of which is from a Nobel Prize winner. Exemplary scholastic record and many community-based volunteer positions. 2. Sponsors, Collaborators, and Consultants:

Two suburb sponsors are listed. Examples Of Sound. Dr. Connors, Chief, HIV-specific Immunity Section NIAID, has a long track record of high quality research and publications and a solid list of successful trainees (4/year for 20 years). The other sponsor, Dr. Sattentau, a Professor of Immunology and Pathology at the University of Oxford, is equally meritorious with over 151 published manuscripts and solid funding record. Dr. Sattentau, also has a established track record of the killer angels, 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. The project is well outlined and there are sufficient preliminary data to support the feasibility of the project.

The plan is to utilize a novel recently developed (Connors lab) quantitative flow cytometric assay to t lymphocytes vs b lymphocytes, measure GrB cytotoxicity and determine which Abs are capable of mediating the the killer angels, highest level of ADCC. Using this technique the applicant plans to what were and consequences civil, characterize the potency of sera from subjects with different rates of disease progression, characterize the specificity and breadth of antibodies with ADCC activity. Using advance microcopy techniques (fixed and the killer live cell laser scanning confocal microcopy and electron microscopy) the applicant plans to 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 virologic synapses. This is a highly ambitious grant.

It may be difficult for the applicant to finish all the proposed work especially the Essay, work proposed in Aim 3. The applicant is calling for 300 subjects but no power calculation is the killer angels shown to support that many subjects. A timeline for the proposed work would be helpful. The Galapagos Essay. 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 the killer house courses and seminar series, lab meetings). Letters describing each institutions role in training the applicant were provided. Applicant states that she will interact on imperialism 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 angels, applicant will be at the NIH for one year and Oxford for one year and then back to medical school for the last 2 years.

This raises some concerns regarding the duration of the funding (3 vs. 2 years). 5. Institutional Environment Commitment to imperialism, Training: The work will be conducted at the NIH/NIAID and University of Oxford. Both institutions are of the highest caliber with access to all the required resources. Angels. 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 Format (Required): On line ethics course at the NIH and formal classroom course at Oxford. Comments on Subject Matter (Required):

Applicant states they will follow principle of information on thomas edison, 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 NIH. Oxford offers a similar course. Comments on Faculty Participation (Required): No comment on faculty participation. Comments on angels Duration (Required): Comments on information edison Frequency (Required):

Online course and the killer angels annual refresher at the NIH. Additional Comments to Applicant (Optional): Fellowship Applicant: 1. Sponsors, Collaborators, and lymphocytes Consultants: 1. Research Training Plan: 2. Training Potential: 1. Institutional Environment Commitment to the killer, Training: 1. Overall Impact/Merit : This proposal comes from an excellent candidate who is part of the NIH/Oxford/Cambridge Scholars program, carrying out her PhD research under the were and consequences of the civil war, 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 the killer, different stages of HIV infection in ADCC (comparing to clinical status and Ab neutralization), (ii) characterize the specificity and breadth of Abs mediating ADCC (comparing the were the causes and consequences civil, sera to panels of known neutralizing Abs), and the killer angels (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 of sound devices a clear and the killer well-written proposal detailing a strategy to carry out relevant research in an excellent training environment. THE FOLLOWING RESUME SECTIONS WERE PREPARED BY THE SCIENTIFIC REVIEW OFFICER TO SUMMARIZE THE OUTCOME OF DISCUSSIONS OF THE REVIEW COMMITTEE ON THE FOLLOWING ISSUES: PROTECTION OF HUMAN SUBJECTS (Resume): ACCEPTABLE. INCLUSION OF WOMEN PLAN (Resume): ACCEPTABLE. INCLUSION OF MINORITIES PLAN (Resume): ACCEPTABLE. INCLUSION OF CHILDREN PLAN (Resume): ACCEPTABLE.

COMMITTEE BUDGET RECOMMENDATIONS: The budget was recommended as requested.

Custom Essay Order -
The Killer Angels (The Civil War Trilogy, #2) by Michael

Nov 11, 2017 The killer angels, write my essays today -

The Civil War Trilogy 3-Book Boxset (Gods and Generals,

Open Access to Electronic Theses and the killer angels Dissertations (ETDs) I finished my dissertation in 1977, before the examples devices web, before the the killer angels internet, and edison even before personal computers. I typed it on angels an Olivetti typewriter and, when my committee accepted it, I paid the department secretary a dollar a page to retype it according to the formatting specs of the university. Imperialism! I was honored when the university made a copy on acid-free paper, bound it in the killer, boards, and put it on the open stacks in the main library. It even had a card in the card catalog. I was also honored when I discovered a week later that someone had stolen the copy from the library. In addition, I sent a copy to University Microfilms International (UMI), which produced priced paper or microfilm copies on-demand. (UMI is now owned by ProQuest.) As far as I know it#x0027;s still accessible for a price from UMI.

I have no idea whether anyone has ever ordered a copy, let alone how many. Unlike some other Ph.D.s (the majority? the minority?) I never mined my dissertation for publications. I was too eager to get on of sound to other projects to publish it as a book or turn any of its chapters into the killer angels articles. So it#x0027;s only accessible today from UMI, on UMI#x0027;s terms. If I had the text in lymphocytes, digital form, I#x0027;d certainly want to make it OA through a suitable repository, but I honestly couldn#x0027;t tell you whether that would violate the agreement I signed with UMI back in 1977. I#x0027;d have to research that question, and I don#x0027;t expect that the research would be easy.

But I don#x0027;t have a digital copy of the text and am not likely to make one any time soon. I know firsthand that dissertation literature is valuable, and not only because my mother and I think I wrote a good one. The Killer! I wrote on a fairly obscure topic for which there wasn#x0027;t much existing literature#x2014;a fairly common phenomenon, given the assignment. But I found a handful of dissertations on neighboring topics in the UMI catalog and causes one was better than every book I found on the same subject. Unfortunately, I had to buy these dissertations in order to read them. I had to buy them even to look at them closely enough to evaluate their relevance.

Dissertations are longer than journal articles and cover their topics more comprehensively. They are more responsive to past literature than journal articles and are usually researched, refined, and revised over a longer period of angels, time. And they#x0027;re not yet salami-sliced into meaningless or trivial snippets. Indeed, they#x0027;re a prime brand of the salami itself. Dissertations are more like preprints than postprints in the sense that they#x0027;re not formally peer-reviewed. But they undergo a kind of review that#x0027;s at least as rigorous. What Were The Causes War! If you#x0027;ve ever refereed a journal article, you know that the job can be done in an afternoon, and often is. Moreover, your name is rarely associated with the the killer published (or rejected) work, and vs b rarely known to the authors or readers. The Killer! This frees referees to information on thomas edison criticize powerful authors of flawed articles#x2014;but it also frees referees to angels trash powerless authors of brilliant articles. It frees referees from accountability. Imperialism! By contrast, your dissertation was vetted by your faculty committee for months or even years.

You know who they are, and so will most readers of the the killer final product. They feel that their own reputations are on the line, almost as much as yours is. That#x0027;s why they willingly devote time and care to reviewing a dissertation and why they rigorously, almost jealously, enforce a high standard. When they certify that you have satisfied the university#x0027;s requirements for originality, contribution to examples devices knowledge, and mastery of the angels relevant literature, their judgment is at devices, least as well-considered, authoritative, and useful as a thumbs up from a journal referee. Instead of devaluing dissertations because they are not formally peer-reviewed, we should see a beautiful win-win situation here. They undergo a review that is the killer sufficiently rigorous to The Galapagos make them good, or to make them worth disseminating and using. But at the same time, their review is sufficiently unconventional (or sufficiently unlike journal review) to carry no publisher#x0027;s investment and the killer angels therefore no publisher#x0027;s resistance to imperialism causes OA.

The Invisibility of Dissertations. Dissertations are not just good, they#x0027;re largely invisible. Libraries rarely hold dissertations not written by their own students. Dissertations are not well indexed. They#x0027;re available for purchase, but difficult to evaluate before purchasing. Moreover, many details from dissertations never make it into the killer angels journal articles, and many dissertation topics are too narrow to justify book publication. In short, dissertations are high in devices, quality and low in accessibility, In fact, I#x0027;d say they constitute the most invisible form of useful literature and the most useful form of invisible literature.

Because of their high quality, the access problem is worth solving . You know what I#x0027;m building up to, but let me get there step by angels, step. Three Degrees of Difficulty in Achieving Open Access. Because OA to copyrighted literature requires the copyright-holder#x0027;s consent, we can rank different bodies of literature according to the ease or difficulty of examples devices, obtaining that consent. The low-hanging fruit#x2014;in the words of the BOAI#x2014;is the literature that #x201C;scholars give to the world without expectation of payment.#x201D; Let#x0027;s say that Phase One of the angels OA movement is to provide OA to information this kind of royalty-free literature. Because its authors don#x0027;t expect to be paid, and write for impact rather than money, they can consent to OA without losing revenue. That makes it much easier for the killer angels scholars to consent to OA than musicians or movie-makers. Phase Two is to provide OA to royalty-producing literature like books. Imperialism Causes! This is the killer angels harder because the copyright holder must be persuaded that OA will either increase sales or bring benefits that outweigh the loss of sales. If you#x0027;ve been following the were of the book-digitizing wars, you know that some authors are persuaded and some are not. Phase Three is to reform copyright law in order to reduce permission barriers. It would help to shorten term of copyright, extend the first-sale doctrine to digital content, restore fair-use rights, nullify clickwrap licenses as contracts of adhesion, and safeguard the angels public domain from further prospective or retroactive enclosure.

But because these steps require legislation, and are opposed by well-funded industries, they are the most difficult of all. Fortunately, they#x0027;re merely desirable and information not necessary for OA. We can get all we need from the killer, Phases One and Two. For cutting-edge research published in Essay, journals, we can get all we need from Phase One. First point: Dissertations are Phase One literature, just like journal articles. Graduate students are not paid for their dissertations and can consent to OA without losing revenue. Their consent is even easier to obtain than the angels consent of faculty members, since dissertations are already subject to t lymphocytes vs b the terms and conditions of the university. If there#x0027;s a difference, it#x0027;s that authors of journal articles know they#x0027;ll never be paid for those texts, but some grad students plan to turn their dissertations into angels books that generate (or could generate) revenue.

I#x0027;ll return to this possibility. But note that it#x0027;s the future book that#x0027;s Phase Two; the dissertation is still Phase One. I#x0027;ve read about 30 university web pages on ETD policies. What#x0027;s remarkable is the way they list the benefits of OA (wider visibility and greater impact) among the benefits of ETDs as if OA were a natural consequence of creating the work in digital form. In principle, universities could require electronic submission of the dissertation without requiring deposit in examples, the institutional repository. They could also require deposit in the repository without requiring OA. But in practice, most universities don#x0027;t draw these distinctions.

Most universities that encourage or require electronic submission also encourage or require OA. What#x0027;s remarkable is that for theses and dissertations, OA is angels not the vs b lymphocytes hard step. The hard step is encouraging or requiring electronic submission. For dissertations that are born digital and submitted in digital form, OA is pretty much the default. I needn#x0027;t tell you that this is not at all the case with journal literature. There are two lessons to the killer angels draw from this. Vs B Lymphocytes! First, anything that fosters ETDs (as opposed to paper TDs) fosters OA to angels ETDs. Second, the call for OA to ETDs is not new.

It#x0027;s been part of the ETD movement since the beginning. Information! If there#x0027;s anything new here, it#x0027;s that I#x0027;m arguing for an OA mandate, not just for OA. Notable, explicit calls for OA to ETDs have already been made by Edward Fox and Gail McMillan (1997), Edinburgh#x0027;s Theses Alive project (2004), JISC#x0027;s Electronic Thesis project (2005), Richard Jones and Theo Andrew (2005), and Arthur Sale (2006). UNESCO#x0027;s ETD project called for #x201C;equal access#x201D; to ETDs in 1999, but this is just another way of calling for OA, since priced access cannot be equal access. The international Digital Access to Research Theses (DART) project is angels committed to OA for ETDs but is The Galapagos Essay just starting up its advocacy efforts. Nine Reasons to Mandate OA for ETDs. Our experience in advocating and implementing OA comes largely from the world of faculty, not the world of grad students. In the world of faculty, the best rationale for angels an OA mandate is to the causes of the war get the attention of authors. Authors control the rate of OA growth, but they#x0027;re not paying attention to angels OA. We can#x0027;t appeal to them as a bloc because they don#x0027;t act as a bloc. It#x0027;s not hard to The Galapagos Islands persuade them, or even excite them, once we catch their attention, but it#x0027;s very hard to catch their attention because they are so anarchical, overworked, and preoccupied.

So we have to work through the institutions that have the the killer angels greatest influence on authors. These arguments apply even more easily to grad students than to faculty: the benefits are just as valuable and causes the barriers much lower. One objection is that a mandate paternalistically coerces students for the killer their own good. If true, this would be a serious problem for me, though perhaps not for everyone who defends mandates. I cannot support paternalism over competent adults, and causes I certainly put graduate students in that category.

Fortunately, the paternalism objection misses the target and is easily answered. (The answer also applies to faculty mandates but here I#x0027;ll elaborate it only for grad students.) First, I only angels support mandates that are conditions on imperialism causes voluntary contracts. The Killer! They might be funding contracts: if you take our money, you#x0027;ll have to provide OA to your research; if this bothers you, then don#x0027;t take our money. They might be employment contracts: if you work here, you#x0027;ll have to information provide OA to your research; if this bothers you, then don#x0027;t work here. An OA mandate for ETDs would belong to the same family. If you attend this university, you#x0027;ll have to provide OA to your dissertation; if this bothers you, then don#x0027;t attend this university. Students who see this as a threat will go somewhere else; students who see it a promise are getting the idea. Second, I only the killer angels support mandates with reasonable exceptions. Were The Causes And Consequences Of The Civil! Grad students who have good reasons to angels be exempt from the mandate should be exempted, not coerced. (More on and consequences civil the exceptions themselves in the next section.) Third, an OA mandate for ETDs advances the university#x0027;s interest, not just the student#x0027;s.

The student interest is greater visibility and impact. The Killer! The university interest is information on thomas that an OA mandate will elicit better work, better show students that the university is taking the dissertation seriously as scholarship, better fulfill the university mission to share the knowledge it produces, and the killer angels better assist researchers elsewhere who could benefit from information edison, this knowledge. In short, the paternalism objection doesn#x0027;t apply because the kind of OA mandate I#x0027;m talking about is the killer angels fundamentally consensual, not coercive, and aims at benefits far beyond the student-authors themselves. An OA mandate for ETDs is no more problematic than other academic requirements and considerably more mission-critical. Today universities seem more interested in mission-trivial details like the margins and font sizes of a dissertation than in its availability to others who could use it, apply it, or build on it. Arthur Sale argues that the examples of sound devices OA mandate should apply to all dissertations submitted as of the killer, a certain date rather than all dissertations by students who enroll as of a certain date. Causes! The two methods differ because students finish their dissertations at different rates. The first method jumps instantly to 100% compliance while the second phases in compliance over the killer angels, a few years. If the The Galapagos Islands primary goal is rapid growth in the body of OA ETDs, then Sale is right to recommend the first method. The drawback of the killer angels, course is that it would change the were and consequences rules for students who are already enrolled. Hence, if it#x0027;s important to preserve a consent or contract basis for the OA mandate, then it#x0027;s better to use the second method, announce the new policy to all new applicants, and apply it only to the killer those who choose to enroll.

On the other hand, the possibility of exemptions (see next section) may introduce a sufficient consent element to let us take Sale#x0027;s recommendation as well. Apart from the web pages of university ETD programs and ETD repositories, here are the sources I found most useful. Paul Ayris, Chris Pressler, and The Galapagos Islands Essay Austin McLean, The DART-Europe Project: Toward Developing a European Theses Portal, presented at the 2005 ETD meeting, Sydney, Australia, September 28, 2005. Charles W. Bailey, Jr., Electronic Theses and Dissertations: A Bibliography, DigitalKoans, July 8, 2005. Charles W. Bailey, Jr., ETD Policies and Procedures at ARL Institutions, DigitalKoans, July 21, 2005. Tim Brody, Registry of Open Access Repositories (ROAR). Also see the the killer angels page of ETD repositories (listing 70 as of causes, June 25, 2006). Edward A. Fox and Gail McMillan, Request for Widespread Access to ETDs, October 1997.

Edward Fox, It is easy for universities to support free culture with digital libraries: The NDLTD Example, presented at the MetaScholar Initiative (Emory University), May 5, 2005. Only the abstract is free online. Richard Jones and Theo Andrew, Open access, open source and e-theses: the development of the Edinburgh Research Archive, Program: electronic library information systems, 39, 3, March 2005, pp. 198#x2013;212. Joan K. The Killer Angels! Lippincott, Institutional Strategies and Policies for imperialism Electronic Theses and Dissertations, Educause Center for Applied Research Bulletin, June 20, 2006. This came out after my June 8 talk in the killer, Quebec, but I wish it had come out earlier. Gail McMillan, Do ETDs Deter Publishers? Does Web availability count as prior publication? A report on information edison the 4th International Conference on Electronic Theses and Dissertations (Caltech, 2001), College and Research Libraries News, v. 62, no. 6 (June 2001). Arthur Sale, The impact of mandatory policies on ETD acquisition, D-Lib Magazine, April 2006.

Arthur Sale, Unifying ETD with open access repositories, in Tony Carneglutti (ed.), Proceedings 8th International Electronic Theses and Dissertations Symposium, Sydney, Australia, 2005. Nancy H. Angels! Seamans, Electronic theses and dissertations as prior publications: what the information edison editors say, Library Hi Tech, March 2003. Brian Surratt, ETD release/access policies in ARL Libraries: a preliminary study, presented at the 2005 ETD conference in Sydney, Australia, September 30, 2005. #x2014;Data for this article. I want to thank Richard Fyffe, Arthur Sale, Brian Surratt, Scott Walter, and above all, Sharon Reeves, for answering my many questions about ETDs over the past many months. This article is based on my keynote address, #x201C;Open Access for ETDs,#x201D; at the 9th International Symposium on Electronic Theses and Dissertations (Quebec City, June 7#x2013;10, 2006). My slides will be online at angels, the site soon. With one exception, everything from my slide presentation and talk is edison present and more fully developed here. The exception is the killer that I had two slides in the talk listing universities with different policies on electronic submission and OA for ETDs.

To see which universities have which policies, see the slides.

Pay for Essay and Get the Best Paper You Need -
The Killer Angels (The Civil War Trilogy, #2) by Michael

Nov 11, 2017 The killer angels, academic proofreading -

The Killer Angels Characters - Shmoop

979 words essay planets and solar system. 979 words essay planets and solar system. 979 words essay planets and solar system. A planet is a celestial body that revolves around a central star and does not shine by its own light. The only planetary system that is known to man is our solar system. It is made up of nine planets. The nine major planets in our solar system are Mercury, Venus, Earth, Mars, Jupiter, Saturn, Uranus, Neptune and Pluto. There are also many other minor planets, which are also in our solar system, but they are unimportant compared to the nine major planets. Mercury, which is the planet that is closest to the sun, is the first and smallest of the inner planets. It is speculated that the heat from the sun made it impossible for the gases present to the killer become part of the examples of sound planetary formation. The Killer Angels. The surface of Mercury is extremely hot.

It is approximately 470 degrees Celsius on the surface and is thought to be even hotter at the two hot spots. These hot spots are on opposite ends of the equator. It is the the causes of the heat of the surface that makes it impossible for Mercury to have any type of atmosphere. Mercury orbits the sun once every 88 days and has a true rotation period of the killer angels 58.6 days. Image Source: vignette1.wikia.nocookie.net. Venus is the second closest planet to the sun and is said to be the most closely resembles to Constructing Essay Earth in size, density, and distance from the sun.

Most scientists know Venus as the sister planet to the Earth. It is called this because it closely resembles the Earth#8217;s mass, density and angels, diameter. The only thing different is that Venus is shrouded in thick clouds that completely hide the surface of the planet. The surface temperature is also much warmer than that of Essay Earth. Venus completes one revolution around the sun in 224.7 days. This makes the Venusian day equal to the killer 117 earth days. It is thought that this slow rotation may be the reason why Venus has no magnetic field. The atmosphere of Venus is made up of 98% carbon dioxide and 2% Nitrogen. Islands Essay. This atmosphere also has the angels presence of t lymphocytes helium, neon and argon.

Mars is the fourth furthest away from the sun and is recognized by its reddish colour. The Killer. Mars is also very much like the Earth. More than any other planet in the solar system, Mars has characteristics that make it an Earthlike world. One thing that is very similar to Earth is the rotation period. Mars rotation period is only thirty-seven minutes longer than the Earth#8217;s. This would explain why Mars has significant seasonal changes just as Earth does.

Mars is extremely hard to understand due to the effect of blurring that is caused by the two atmospheres of Mars. It is also known that dust storms are prevalent and leaves the surface of Mars covered by a red haze. Jupiter is the fifth planet and is the most massive of all the planets in imperialism causes, this solar system. The Killer Angels. Its mass represents more than two-thirds of the total mass of all the planets, or 318 times the mass of the Constructing Earth. Jupiter#8217;s density is quite low at 1.3 g/ cubic cm. The atmosphere of the killer Jupiter contains water, ammonia, methane and carbon. It is thought by scientists that there are three cloud layers. The wind activity on Jupiter is what civil, quite fierce and moves in jet streams parallel to the equator. The weather on Jupiter is still very hard for scientists to understand. There is not enough information to truly understand how the weather is on this planet.

Jupiter is surrounded by rings of light which is very prominently visible to earth. The ring particles must generally be about as big as the wavelength of the killer light, that is, only a few microns. That is why these rings are faint or diffuse. The rings are what Jupiter is known for. Saturn is a planet which is also known for examples devices its rings and when viewed has a yellow or greyish color. The color is the killer angels, from the gaseous atmosphere and the dust particles in that atmosphere. The atmosphere is mostly a clear hydrogen- helium atmosphere. There are also traces of methane, phosphine, ethane, and acetylene. This atmosphere is much different than that of the Earth#8217;s. Saturn orbits the The Galapagos Essay sun with a period of 29.4577 tropical years. It is 1.427 billion Km away from the sun and is therefore a cold planet.

It has an equatorial diameter of 120,660 Km, which makes it the second largest planet in our solar system. Angels. The next planet is Uranus. The main problem scientists have with Uranus is that, die lack of visible surface features means that it is difficult to measure the rotation period of Uranus (Hunt/Moore, 388, 1983). Uranus has an equatorial diameter of imperialism causes 51,000 Km, which is almost four times as much as Earth. The atmosphere is made up of mostly methane gas and therefore the planet has a red tint or a bluefish green color. Uranus also has rings but unlike Saturn these rings have almost no small particles. Neptune is the last of the gaseous planets in our solar system.

Its atmosphere is much like Uranus#8217;s because it is mostly helium and the killer angels, hydrogen. It also contains methane. Were The Causes Of The Civil War. Neptune has a diameter of 49,500 km and a mass 17.22 times that of the Earth. It has an average density of 1.67 /cm 3 . Neptune also has rings like its other gaseous partners, but they are very faint. Not a great deal is known about Neptune. The final planet, which is also the smallest and the furthest away from the sun is the killer angels, Pluto. This planet is very hard to see therefore not a lot is known about devices, its physical characteristics. Scientists do know that it has a thin methane atmosphere. Little is known about this planet because it is the killer angels, so far away from die Earth and the sun.

Scientists are always learning new things and information on thomas edison, more data will arise in the future. Welcome to Shareyouressays.com! Our mission is to provide an online platform to help students to discuss anything and everything about Essay. This website includes study notes, research papers, essays, articles and other allied information submitted by the killer angels visitors like YOU. Before publishing your Essay on this site, please read the causes following pages:

Order Your Own Writing Help Now -
The Killer Angels - Shmoop

Nov 11, 2017 The killer angels, how to buy essay cheap with no worries -

The Killer Angels Summary - Shmoop

Do You Underline Movie Titles In An Essay. Do You Underline Movie Titles In An Essay. Do You Underline Movie Titles In An Essay. The cost-effective price means no quality compromise! We all have walked miles in angels, students shoes and we do realize your needs. Our service is Essay interested in providing help in essay writing for different students, and each client is equally important to us.

The service we have created presents an easy-to-use platform to the killer buy essay online and to information on thomas receive the exact essay you need. Our site presents a vast choice of the options. With us you are provided with a chance to take active part in writing your essay. The objective of our service is satisfying the needs of the clients, which means that your preferences, comments, and angels, instruction will be carefully followed. Youre always running out of time especially when you are at Islands Essay, college.

Colleges and universities can load you with the tons of essays, and sometimes it is hard to understand where to the killer angels start from. Students often face situations when they have a solid theoretical background, but encounter problems with the text structuring. Or sometimes, the approaching finals are always a stressing period which can influence the process and examples of sound, quality of your essay. In order to conduct a successful study, the angels concentration and Constructing and Reconstructing, efforts have to be maximized. Our team consists of angels people who are into devices dealing with extreme situations and challenges head on. Working on the verge of the opportunities is our pleasure. The writers are not afraid of: Time constraints Levels of complexity Essay types The volume of the killer research.

Why should I buy college essays from of sound devices, your site? College time is priceless. However, some teachers seem to be merciless: the amount and scrupulosity of the instructions provided for essay writing is overwhelming. Every teacher has his own understanding of the final assignment and knows what he/she wishes to the killer get. That is the causes of the civil why the degree of instructions fulfillment directly affects the the killer angels mark and, consequently, may influence your academic future. You dont have to worry about it with our site when buying essays online! Our writing teams strengths are extreme attentiveness and mindfulness. No detail will be missed. We share the same objectives with our clients to prepare the vs b lymphocytes best essay possible. Angels! For this purpose, it is very important for our clients to provide the Constructing complete and utter information concerning your essay. Angels! We hope for our win-win collaboration each time you buy essays online cheap!

Buying essay from were the causes and consequences civil, our site usually looks as follows: Each instruction field must be thoroughly filled, so our writers get the full picture of the essay you need Attach the files if necessary You may contact us 24 / 7 and inform about any clarifications or additional details The choice of the author is in your hands. You can continue working with the the killer angels chosen writer, your preferences will be saved and taken into account You are free to ask for a draft of your essay and Essay, stay involved in the killer angels, writing process and monitor the progress Despite the vs b professionalism of our writers, each essay is carefully checked by the Quality Assurance Department to angels make sure you get the best paper Anti-plagiarism is the Essay core principle: we make sure the essay is 100 percent unique the plagiarism possibility is excluded You receive your essay Receive an A-stamped paper! Why we offer to buy our essays online cheap? Our writers look at each essay through the prism of knowledge, solid research background, argumentation, and critical approach. The philosophy of our company outlines the highest quality, student satisfaction and exceeded expectations and put these attributes before the the killer financial benefit.

We are the vs b best choice in essay emergency! Our writers can be challenged with the urgency up to several hours, and the killer, you wont be disappointed. We approach writing your essays in a special way, because we are used to think different. The authors are not only savants in information on thomas edison, their field; they are also professional writers, who can provide perfectly structured text. The Killer Angels! Your essay will be different from the other soulless works. It will showcase the real thinking process and information on thomas, will have the sparkle that will be definitely evaluated by the killer, your teacher. Our writers are professionals, and each essay is treated equally seriously. The efforts used for the college essay, high school essay, or dissertation are the same. If you lack time or cannot write your essay for any other reason our service is to stand by! All the papers you get at englishessays.net are meant for research purposes only.

The papers are not supposed to The Galapagos be submitted for academic credit. should be there! Terms conditions Privacy policy Referral program. Please read these Terms and Conditions (Terms and/or Terms and Conditions) carefully before using the the killer englishessays.net website (Website). Your access to and use of Website are conditioned on your full acceptance and compliance with these Terms and Conditions and examples of sound, this Website Privacy Policy, which are published at the killer angels, englishessays.net and imperialism causes, which are incorporated herein by reference (Privacy Policy). These Terms and Conditions and Privacy Policy are applied to all visitors, users and others who access or use this Website.

By accessing or using this Website, you agree to the killer angels be bound by these Terms and Conditions and Privacy Policy. If you disagree with these Terms and Conditions and/or Privacy Policy or any part of them, you must not use this Website. Capitalized terms defined in vs b lymphocytes, these Terms and Conditions shall have no other meaning but set forward in angels, this section. The following terminology is applied to were and consequences civil these Terms and Conditions, Privacy Policy and Refund and Revision Policy: Client, You and Your refers to you, the person accessing this Website and accepting these Terms and Conditions. The Killer Angels! We, Us and imperialism, Ourselves refers to the killer englishessays.net website. Any use of the information edison above terminology or other words in the singular, plural, capitalization and/or he/she or they, are taken as interchangeable and the killer angels, therefore as referring to same. By using our Services, you represent and Constructing Essay, warrant that (a) all registration information you submit to englishessays.net is truthful and accurate; (b) you will maintain the accuracy of such information; (c) you are 18 years of age or older and/or have full legal capacity to enter into the killer legally binding relations; and (d) your use of the Services does not violate any applicable law, regulation, and/or your college/university/school rules. Your profile may be deleted and t lymphocytes vs b, Services provided to you may be terminated without warning, if we believe that you are less than 18 years of age and/or do not have full legal capacity to enter into legally binding relations. Subjected to full compliance with these Terms and Conditions, englishessays.net shall provide academic writing services as described more fully on angels, the Website (Services). Services may include, but not be limited to, providing our Clients with dissertations, research papers, book reports, term papers, and other types of assignments written by englishessays.net team (Paper) which are intended for research/reference purposes and for your personal use only.

Services may include editing, proofreading, paraphrasing, or formatting existing papers of our Clients. Please note that rewriting an on thomas, existing paper that contains 40% or more plagiarized content may qualify as providing you with a custom Paper and the killer, shall be charged for Islands accordingly. Please note that Services may be provided only to the users who submit an appropriate order form at the Website and angels, englishessays.net may charge fees for examples of sound devices such Services. The Services are provided according to the provisions of these Terms and Conditions and the specific commercial provisions and policies (including Privacy Policy, Refund Policy, etc.) as detailed on the killer angels, the Website, and these provisions and what the causes of the war, policies may be amended or changed from time to time. The format of the Papers we provide: 12 point Times New Roman;

Bibliography on a separate page; Approximately 250 words per angels, page; One inch margin top, bottom, left, right; Title and Reference pages are free of charge. In case Client needs a single-spaced Paper they are to pay a double fee. The standard Paper formatting includes a Title page , main content of the Paper, and a Reference page. Note that you pay only for t lymphocytes the main content of the the killer Paper, while a Title page and a Reference page are provided free of charge. englishessays.net reserves the right to use any relevant materials available, such as books, journals, newspapers, interviews, online publications, etc., unless the Constructing Essay Client indicates some specific sources to be used. PLACING AN ORDER. When placing your order, you must provide accurate and complete information. You are solely responsible for any possible consequences and misunderstandings, in angels, case you provide us with inaccurate and/or incorrect and/or unfaithful information.

Please be advised that you will be asked to give final confirmation to the instructions you provide in order details. Your Paper instructions should be confirmed in what the causes and consequences of the war, your Order Tracking Area within 3 hours after placing your order (and within 1 hour for orders with urgency less than 24 hours). Orders without instructions will not be worked on and may be delayed and you accept sole responsibility for the killer angels such delay. englishessays.net guarantees that the delivered Paper will meet only confirmed requirements. You must not change the instructions once you have confirmed them. Any alterations to confirmed instructions are considered as additional order, thereby requiring additional payment. All payments are due upon imperialism, receipt. If the payment is not received or payment method is the killer declined, the Client forfeits of Services. All fees are exclusive of all taxes and/or levies, and/or duties imposed by taxing authorities, and you shall be responsible for payment of all such taxes and/or levies, and/or duties.

You agree to pay any such taxes that might be applicable to on thomas edison your use of the Services and the killer angels, payments made by you under these Terms. If at any time you contact your bank or credit card company and decline or otherwise reject the lymphocytes charge of any payment, this act will be considered as a breach of your obligation hereunder and your use of the Services will be automatically terminated. Use of stolen credit card and/or any credit card fraud is angels considered to edison be a serious crime. The Killer! englishessays.net closely cooperates with our payment provider to prevent and of sound, fight online fraud. In case of any online fraud, appropriate state authorities will be contacted immediately. By doing a chargeback, you agree to give up all your rights to the Paper automatically. At the same time, you authorize englishessays.net to publish the completed Paper and start the authorship procedure that will allow us to angels determine if you have used any parts of the examples devices Paper.

The procedure may include contacting your school officials and/or posting your full details along with the completed Paper online. englishessays.net reserves the right to change its prices at any time in its sole discretion and such changes or modifications shall be posted online at the Website and become effective immediately without need for further notice to any Client and/or user. We care about our Clients and are always looking for ways to offer them the best value for money. One method we use is a discount system. The Killer Angels! englishessays.net, at its sole discretion, shall have the right to provide our Clients with discount programs as described more fully and published on the Website. According to our loyalty program, you earn back 10% of your total bill in Points (1 currency unit (inter alia USD/ EUR/ GBP etc.) = 1 Point) after you make your first order. Your Points are accumulated on The Galapagos, your Credit Balance. Credit Balance is an account for the killer Points of a Client which can be used for future purchases on the Website exclusively. Imperialism! You can use your Points for your next purchases on the Website exclusively. Your Points cannot be refunded. The discount may be obtained by the use of the promo code. The amount of Points added to the Credit Balance is calculated on the basis of the the killer angels order price excluding the applied discount (if any).

Later, 5% of every next order (not including credits) is added to your Credit Balance. englishessays.net will issue a refund to you only according to these Terms. englishessays.net offers a 14-day money back period for Papers less than 20 pages and a 30-day period for Papers more than 20 pages (Refund Period). Refund Period begins on the date of Client`s order deadline and t lymphocytes vs b lymphocytes, expires on the last day of the Refund Period. In case you are not satisfied with any of the Services, you can submit a refund request according to these Terms within the Refund Period. The Killer! Once the Refund Period elapses, englishessays.net will not refund any amounts paid. If the order is examples of sound devices not completed and/or the Paper is not downloaded or delivered in the killer angels, its complete form by or to you, the full refund is issued at any time. In the event of order cancellation, the funds will be debited back only to the account of the vs b lymphocytes initial payment within 5-7 business days from the time of cancellation request. In other case englishessays.net assesses refund requests on a case-by-case basis as there are usually unique reasons as to why a refund request is made. Please note that if you request a refund, we may require documented proof that the quality of your order is low (e.g., scan copy of the killer your instructors feedback, plagiarism report, etc.).

Should you feel it necessary to make a refund request, we will immediately forward your order to our Quality Assurance Department. After comparing their findings with the reasons for dissatisfaction, the were and consequences civil war necessary corrective actions will be taken. The Killer Angels! Any refund request must be made within the Refund Period. In case englishessays.net reimburses the money because of mistakes or some irrelevance to the initial instructions, our Quality Assurance Department, at its sole discretion, evaluates the information edison quality of the Paper and refunds an angels, amount comparable to the percentage of incorrect content in The Galapagos Islands, the Paper and mistakes present in angels, it. englishessays.net provides various methods of contact (i.e. email, telephone, message board, and live chat) to facilitate communication between you, us and the writer assigned to complete an order. Using any of these methods, our Customer Support Center is causes available to angels you at Constructing and Reconstructing Essay, any time and will respond to any refund request or other issue promptly. However, if such a request is not received using any of the aforementioned methods within the the killer Refund Period, englishessays.net will not be obliged to honor or consider the and Reconstructing above said request.

Should the Paper delivery be delayed due to unexpected circumstances, from the side of englishessays.net, we may provide compensation for the breach of the order deadline in the form of a credit or a discount to be used towards your next order with us. Please be informed that delivery time deviation is not a subject to the killer angels refund. Any revision request or complaint in regards to a Paper that englishessays.net has provided must be made within the and Reconstructing revision period (Revision Period). englishessays.net offers a 14-day Revision Period for Papers less than 20 pages and a 30-day period for Papers more than 20 pages. Revision Period begins on the killer, the date of Client`s order deadline and expires on the last day of the Revision Period. After that point, no revision and/or complaint will be accepted. englishessays.net recognizes that orders vary in size and complexity; as a result, dissertation, thesis and/or other sufficiently large assignment may be granted 30-day Revision Period. Sufficiency in the size of the Paper will be determined by englishessays.net in its sole discretion.

In case a request for revision is not submitted within the Revision Period, englishessays.net tacitly accepts that the Client is satisfied with the Paper and requires no further actions to be taken in regards to the Paper unless extra payment is provided or a new order is placed. Upon receiving your completed assignment you are entitled to a free revision should the Paper fail to meet your instructions or defined the requirements in information on thomas edison, any way. The Killer Angels! When this is the case, you are entitled to request as many revisions as may be required to make the Paper consistent and compliant with your instructions. During the Revision Period the request for revision may be made at any time. All revisions must be based on the original order instructions. What Of The War! If at angels, the time of the revision request you provide new, additional, or differing instructions, this will be interpreted as an application for examples new Paper and thus, will require an additional payment. The Killer! Furthermore, should you request a revision after the Revision Period, it will also be considered as a new order requiring an additional payment.

We may require you to Constructing supply us with personal identifying information, and we may also legally consult other sources to obtain information about you. By accepting these Terms and the killer angels, Conditions, you authorize us to make any inquiries we consider necessary to validate the information that you provide us with. We may do this directly or by edison, verifying your information against third party databases; or through other sources. Essentially, verification procedure involves, inter alia, confirming that the the killer order is authentic and that the The Galapagos Islands cardholder is aware of charges by the killer angels, placing a phone call to them, and in certain cases by requesting some additional documents to be submitted for verification to our Risk Department. Examples Devices! In order to ensure timely delivery of your order, this procedure must be completed quickly and angels, without delay. Therefore, it is vital to provide accurate and valid phone numbers. Failure to verify an order may result in order cancellation or the order being placed on hold. You consent to The Galapagos Islands Essay our processing your personal information for the purposes of providing the the killer Services, including for verification purposes as set out herein. You also consent to vs b the use of such data for communicating with you, for statutory and accounting purposes. You acknowledge that you have read and consented to englishessays.net's Privacy Policy. LIMITATIONS OF LIABILITY.

englishessays.net will not be liable to you in the killer, relation to the contents of, the use of, or otherwise in connection with, this Website: for failure to learn the vs b lymphocytes material covered by the Paper; and. for your final grade; and. for the outcome or consequences of submission the Paper to any academic institution; and. excludes all liability for damages arising out of or in connection with your use of this Website. The latter includes, without limitation, damage caused to the killer angels your computer, computer software, systems and examples of sound, programs and the killer, the data thereon, or any other direct or indirect, consequential and incidental damages. The Paper provided to the causes and consequences civil you by angels, englishessays.net remains our property and of sound, is the subject to copyright and other intellectual property rights under local and the killer angels, international laws conventions. The Paper is imperialism intended for your personal use only and it may not be used, copied, reproduced, distributed, transmitted, broadcast, displayed, sold, licensed, or otherwise exploited for any other purposes without our prior written consent. You agree not to engage in the use, copying, or distribution of Papers other than expressly permitted herein.

We post Clients` testimonials on our Website which may contain personal information (first name or initials). Hereby by the killer, accessing or using this Website, you provide us with your consent to post your first name/initials along with your testimonial on our Website. We ensure our posting these testimonials does not interfere with your confidentiality. T Lymphocytes Lymphocytes! If you wish to request the the killer removal of your testimonial, you may contact us at [emailprotected] NOTIFICATION OF CHANGES. englishessays.net reserves the right to change these Terms and Conditions at any time and your continued use of the Website will signify your acceptance of any adjustment, improvements and/or alterations to these Terms and Conditions. You are, therefore, advised to re-read these Terms and Conditions on a regular basis. This web site is owned and examples devices, operated by the killer angels, Viatta Business Ltd. HEXO+ Self-Flying Camera Drone, with a suggested retail price of $1,249.00 USD (Main prize). FreePage (single use) SMS inform (single use) Plagiarism Report (single use) 50$ to your bonus balance which you can use in 365 days 100$ to your bonus balance which you can use in 365 days. 2. Promotional Period.

The promotion begins on 7.18.2017, at 9:00 am and ends on 7.28.2017 at 10:00 pm. This Privacy Policy (Policy) describes how information about t lymphocytes You is the killer collected, used and The Galapagos Essay, disclosed and the killer angels, provides other important privacy information, describes when and The Galapagos Islands Essay, how we may change this Policy, and tells You how to contact us with any questions or comments. We collect information about You and computer(s) You use when You use our Services or otherwise interact with us. Personal Information means information that we directly associate with a specific person or entity (for example: name; addresses; telephone numbers; email address; payment information; device location etc.). Client, User, You and Your refers to you, the person accessing this Website and accepting these Privacy Policy. Any use of the angels above terminology or other words in t lymphocytes, the singular, plural, capitalization and/or he/she or they, are taken as interchangeable and the killer angels, therefore as referring to t lymphocytes lymphocytes same. HOW INFORMATION ABOUT YOU IS COLLECTED.

We collect information about You in three primary ways: Information You Provide. We collect information that You provide to us when You apply for and use and/or purchase our Services or otherwise communicate with us. For example, some of the the killer ways You may provide information to us include: When You purchase our Services, the payment system will require your personal, contact, billing and credit information. When You establish or modify Your user account online, We may collect user identification information, passwords, and/or security question responses that You will use for future sign-on. When You interact with our Customer Service representatives, enter information on our Website, submit survey responses, or pay for Services, we may also collect Personal Information and other information. Islands! We may monitor and the killer, record phone calls, e-mails, live chats, or other communications between You and our Customer Service representatives or other employees or representatives. Information We Collect Automatically.

We automatically collect a variety of were the causes and consequences of the information associated with Your use of the killer our Services. Each time You visit the Website, Personal Information is Constructing and Reconstructing Essay automatically gathered. The Killer Angels! In general, this information does not identify You personally. Examples of automatically collected personal information include, but are not limited to: IP address, Collection Date, Publisher Name, Connection Speed, Day of the causes and consequences war Week Time of Day (hour), Language settings, Country, City (relating to IP address, if available). For example, some of the ways we may automatically collect information include: Cookies and the killer angels, similar technologies. A cookie is a small text file that a web site can place on Your computer's hard drive in order, for what the causes and consequences of the civil war example, to collect information about Your activities on the Website.

The cookie transmits this information back to angels the Website's computer, which, generally speaking, is the only computer that can read it. On Thomas! We need to use cookies on the Website to enhance the the killer user experience and were the causes and consequences civil, avoid multiple logins or password authentication requests. We may use, or we may engage third-parties to use on our behalf, cookies or similar web tags (small data text files placed on your computer or device) or similar technologies to identify Your computer or device and record Your preferences and other data so that our Website can personalize Your visit(s), see which areas and features of our Website are popular, and the killer angels, improve our Website and Your experience. Depending upon Your computer, You may be able to set Your browser(s) to reject cookies or delete cookies, but that may result in what the causes and consequences civil, the loss of some functionality on the Website. We may also use web beacons (small graphic images on a web page or an HTML e-mail) to monitor interaction with our websites or e-mails. Web beacons are generally invisible because they are very small (only 1-by-1 pixel) and the same color as the background of the web page or e-mail message. Web Browsing Activity. When accessing our Website, We automatically collect certain information about Your computer and angels, Your visit, such as your IP address, browser type, date and time, the web page You visited before visiting our Website, Your activities and purchases on our Website, and information on thomas edison, other analytical information associated with the Website. Information From Other Sources. We may also obtain information about You from the killer angels, other sources.

For example, We may receive credit information from and Reconstructing Essay, third-party sources before initiating Your service. We may also purchase or obtain Personal Information (for example, e-mail lists, postal mail lists, demographic and marketing data) from others. HOW WE USE INFORMATION WE COLLECT ABOUT YOU. We use the information We collect for a variety of angels business purposes, such as: To provide and bill for Islands Services You purchase; To deliver and confirm Services You obtain from us; To verify Your identity and maintain a record of angels Your transactions and interactions with us;

To provide customer services to You; To create, modify, improve, enhance, remove or fix our Services and their performance; To identify and suggest products or services that might interest You; To make internal business decisions about Essay current and future Service offerings; To provide You customized user experiences, including personalized Services offerings; To protect our rights, interests, safety and the killer angels, property and that of imperialism our customers, service providers and other third parties; and. To comply with law or as required for legal purposes. We may use Personal Information for investigations or prevention of fraud or network abuse. We may use information we collect to contact You about our and/or third-party products, services, and offers that We believe You may find of interest. We may contact You by telephone, postal mail, e-mail, or other methods.

You may see advertisements when You visit our Website. We may help advertisers better reach our customers by providing certain customer information, including geographic information, language preferences or demographic information obtained from other companies. Angels! This information is used by advertisers to determine which ads may be more relevant to You. However, we do not share Personal Information outside of our corporate family for advertising purposes without Your consent. WHEN WE SHARE INFORMATION COLLECTED ABOUT YOU. We do not sell, license, rent, or otherwise provide Your Personal Information to unaffiliated third-parties (parties outside our corporate family) without Your consent. Imperialism! We may, however, disclose Your information to unaffiliated third-parties as follows: With Your Consent. We may disclose Personal Information about You to third-parties with Your consent.

We may obtain Your consent in writing; online, through click-through agreements; when You accept the terms of disclosures for certain Services; orally, when You interact with our customer service representatives. We encourage You not to share Your password. The Killer! If You provide Your user account password and/or security question responses to what were the causes of the war third parties they will have access to Your Personal Information when they access Your user account with Your account password. To Our Service Providers. We may disclose information to angels third-party vendors and partners who complete transactions or perform services on our behalf (for example, credit/debit card processing, billing, customer service, auditing, and marketing). In a Business Transfer.

We may sell, disclose, or transfer information about devices You as part of angels a corporate business transaction, such as a merger or acquisition, joint venture, corporate reorganization, financing, or sale of company assets, or in the unlikely event of insolvency, bankruptcy, or receivership, in which such information could be transferred to third-parties as a business asset in the transaction. For Legal Process Protection. We may disclose Personal Information, and other information about You, or Your communications, where we have a good faith belief that access, use, preservation or disclosure of such information is reasonably necessary: to satisfy any applicable law, regulation, legal process or enforceable governmental request; to enforce or apply agreements, or initiate, render, bill, and collect for services and products (including to what were the causes collection agencies in the killer angels, order to obtain payment for our products and services); to protect our rights or interests, or property or safety or that of others; in connection with claims, disputes, or litigation in court or elsewhere; to facilitate or verify the appropriate calculation of taxes, fees, or other obligations; or. in an of sound, emergency situation. We may provide information that does not identify You personally to third-parties for marketing, advertising or other purposes. HOW WE STORE AND PROTECT THE INFORMATION COLLECTED ABOUT YOU. Protecting Your Information. We use a variety of physical, electronic, and procedural safeguards to the killer angels protect Personal Information from unauthorized access, use, or disclosure while it is under our control. Unfortunately, no data transmission over the internet can be guaranteed to devices be completely secure. As a result, although we will utilize such measures, we do not guarantee You against the loss, misuse, or alteration of Personal Information under our control, and the killer, You provide Personal Information to us at Your own risk.

You should always take care with how You handle and disclose your Personal Information and were the causes and consequences war, should avoid sending Personal Information through insecure e-mail, social networks or other internet channels. Retention and Disposal. We retain information only for as long as we have a business or tax need or as applicable laws, regulations and/or government orders allow. When we dispose of Personal Information, we use reasonable procedures designed to erase or render it unreadable (for example, shredding documents and wiping electronic media). PRIVACY POLICY UPDATES. How We Communicate Changes to This Policy. We may update this Policy at any time to provide updates to or clarification of our practices. Angels! If we make changes we may provide You with additional notice (such as adding a statement to the homepage of our Website or sending You a notification). You should refer to Islands this Policy often for the latest information and the killer, the effective date of any changes. This web site is owned and operated by Viatta Business Ltd . A Partner is an individual who refers customers. A Referral is an individual who requests a service via the referral link given by a Partner.

With the first order, a Referral acquires a 15% discount on examples, the order, while a Partner receives $50 to the Referral Balance. With further purchases, a Partner earns 5% of the Referrals total order price. All money earned with the Referral Program is stored on your Referral Balance. A Partner can transfer the money to the Bonus Balance and use it to purchase a service. It is possible to transfer the sum to the Partners PayPal account (no less than $20).