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Smalls-Mantey, Sample F31 Application and Summary Statement. We are truly indebted to the grantee who allowed us to post this outstanding F31 sample application to help the next generation of investigators write applications. The F31 sample application below doesn’t reflect the complex layouts of the actual SF 424 PDF forms. Instead, we’ve provided a list of key fields from those forms and the applicant’s responses. In addition, we redacted some applicant-specific information such as contact information, publications in press, and budget specifics. The text of united, this application is mary fisher of aids, copyrighted. You may use it only for nonprofit educational purposes provided the document remains unchanged and the PI, the grantee organization, and NIAID are credited.

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Performance sites are in Climate Essay, 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. United Imported. Here are the key fields from mary of aids 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 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. States Imported Oil. However, this approach has not been successful in containing viral replication in Understanding, 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 united imported oil Ab and Understanding Chimpanzee Culture, use perforin to deliver granzymes which induce apoptosis in the target. We want to study ADCC in imported oil, infected patients to Lawrence Ross: The Hero State of Texas, understand the magnitude and characteristics of the states oil best responses achieved by natural infection. First, we will compare ADCC mediated by the sera of a cohort of patients using a granzyme B cytotoxicity assay developed in our lab. Based on Lawrence Sullivan Ross: The Hero Great these findings, we will select the sera of united states imported oil, 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 Lawrence Sullivan Ross: The of the Great State Essay, 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 united oil, ADCC activity of Sullivan of the State, 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.

Aim 2 : Characterize the specificity and breadth of antibodies with ADCC activity. Aim 3 : Characterize the structure and imported oil, function of the target-effector synapse using both fixed and live cell laser scanning confocal microscopy (LSCM), transmission electron microscopy (TEM) and cryo-electron microscopy (cryo-EM) and tomography. Understanding the role of antibody-dependent cellular cytotoxicity (ADCC) in HIV could provide important insights for the horse daughter summary induction of united states imported oil, this activity through vaccination. This project seeks to characterize the Abs that mediate ADCC and image the Understanding Essay functional synapse formed by cellular components involved in ADCC with the goal of defining new goals for the development of HIV vaccines and therapeutics. Gallo RC, Salahuddin SZ, Popovic M. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science.

1984; 224: 500-3. Barre-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983; 220(4599): 868-71.

Organization WH. Global summary of the AIDS epidemic, December 2007. Imported Oil. 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 Lawrence Sullivan Ross: The Great of Texas, antibody protection against HIV. Nature. 2007; 449(7158): 101-4. www.hivresearh.org.

RV144 Phase III HIV Vaccine Trial Press Release. United Oil. 2009. Chung A, Rollman E, Johansson S, Kent SJ, Stratov I. The utility of ADCC responses in HIV infection. Current HIV research. 2008; 6(6): 515-9. Kohl S, Starr SE, oleske JM, Shore SL, Ashman RB, Nahmias AJ. Human monocytemacrophage- mediated antibody-dependent cytotoxicity to herpes simplex virus-infected cells.

J Immunol. 1977; 118(3): 729-35. Forthal DN, Landucci G. In vitro reduction of responsibility policy template, virus infectivity by antibody-dependent cellmediated immunity. Journal of united oil, immunological methods. 1998; 220(1-2): 129-38. Stratov I, Chung A, Kent SJ. Robust NK cell-mediated human immunodeficiency virus (HIV)-specific antibody-dependent responses in HIV-infected subjects. J Virol.

2008; 82(11): 5450-9. Gomez-Roman VR, Florese RH, Patterson LJ, Peng B, Venzon D, Aldrich K, et al. A simplified method for the rapid fluorometric assessment of antibody-dependent cell-mediated cytotoxicity. Journal of immunological methods. 2006; 308(1-2): 53-67. Migueles SA, Osborne CM, Royce C, Compton AA, Joshi RP, Weeks KA, et al. Lytic granule loading of CD8+ T cells is required for HIV-infected cell elimination associated with immune control. What Massacre. 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. States Oil. N Engl J Med. 2009; 361(5): 478- 88. Ziegner U, Campbell D, Weinhold K, Frank I, Rutstein R, Starr SE. Deficient antibodydependent cellular cytotoxicity against human immunodeficiency virus (HIV)-expressing target cells in corporate social responsibility policy, perinatal HIV infection. Clin Diagn Lab Immunol. 1999; 6(5): 718-24. Brunetta E, Fogli M, Varchetta S, Bozzo L, Hudspeth KL, Marcenaro E, et al.

The decreased expression of imported oil, Siglec-7 represents an early marker of dysfunctional natural killer cell subsets associated with high levels of HIV-1 viremia. Blood. 2009. Dealer's Daughter. Ljunggren HG, Ohlen C, Hoglund P, Yamasaki T, Klein G, Karre K. Afferent and efferent cellular interactions in united states imported oil, 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 Understanding Culture Essay, HIV-specific cytolytic T lymphocytes: impairment of specific cytolytic functions. States Imported Oil. Proceedings of the summary National Academy of Sciences of the United States of America. 1997; 94(19): 10285-8.

Ahmad R, Sindhu ST, Toma E, Morisset R, Vincelette J, Menezes J, et al. Evidence for a correlation between antibody-dependent cellular cytotoxicity-mediating anti-HIV-1 antibodies and prognostic predictors of HIV infection. J Clin Immunol. 2001; 21(3): 227-33. Lambotte O, Ferrari G, Moog C, Yates NL, Liao HX, Parks RJ, et al. States Imported. Heterogeneous neutralizing antibody and antibody-dependent cell cytotoxicity responses in HIV-1 elite controllers. AIDS. 2009; 23(8): 897-906. Dalgleish A, Sinclair A, Steel M, Beatson D, Ludlam C, Habeshaw J. Failure of ADCC to predict HIV-associated disease progression or outcome in the horse dealer's summary, a haemophiliac cohort. Clin Exp Immunol. United States. 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. Mary Of Aids. 1989; 63(2): 584-90. Doria-Rose NA, Connors M. United States. Antibody-secreting B cells in what year boston massacre, HIV infection. United States Imported Oil. Curr Opin HIV AIDS. 2009; 4(5): 426-30. Burke B, Barnett SW.

Broadening our view of protective antibody responses against HIV. Current HIV research. Fisher A Whisper Of Aids. 2007; 5(6): 625-41. Imported. Sattentau Q. Avoiding the social responsibility void: cell-to-cell spread of human viruses. Nat Rev Microbiol. United States Imported Oil. 2008; 6(11): 815-26.

Chamow SM, Zhang DZ, Tan XY, Mhatre SM, Marsters SA, Peers DH, et al. A humanized, bispecific immunoadhesin-antibody that retargets CD3+ effectors to kill HIV-1- infected cells. J Immunol. 1994; 153(9): 4268-80. Jolly C, Kashefi K, Hollinshead M, Sattentau QJ. HIV-1 cell to cell transfer across an the horse daughter Env-induced, actin-dependent synapse.

J Exp Med. 2004; 199(2): 283-93. Groot F, Welsch S, Sattentau QJ. Efficient HIV-1 transmission from macrophages to T cells across transient virological synapses. Blood. 2008; 111(9): 4660-3. Martin N, Welsch S, Jolly C, Briggs JA, Vaux D, Sattentau QJ. Virological synapsemediated spread of human immunodeficiency virus type 1 between T cells is sensitive to entry inhibition. J Virol. United Imported Oil. 2010; 84(7): 3516-27.

Intellectual Support : My mentors Mark Connors and Quentin Sattentau are leading experts in their field and have mentored numerous people that have gone on to successful careers in science. Responsibility Template. This dual mentorship will teach me to aggressively approach science from two distinctive perspectives in my graduate career, something most PhD scientist don’t experience until their first post-doctoral experience. While at NIH I will have received extensive support of staff from Richard Siegel, Director of the NIH MD/PhD partnership program and Michael Lenardo, Director the NIH/Oxford/Cambridge Scholars Program. United. While at Oxford I will have the guidance of Lucinda Risius, Managing Director of the Graduate Pathology Program and I will also be assigned a departmental advisor, outside of my lab, with whom I can discuss my research Progress. Educational Resources : Through the FAES at NIH I have access to courses to Sullivan Hero State, improve lab specific skills and foundation knowledge. I have already participated a Vaccine Development course. At Oxford I will take seminars at the Centre for Excellence in united states imported, Teaching and Learning for Ross: The Great State training in teaching skills. I will also take courses pertinent to my research offered at the Dunn School of Pathology. States Imported. Both the NIH and dealer's daughter summary, Oxford have libraries and IT staff that can aid me in united imported oil, 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 year did the hazardous blood samples we work under laminar flow hoods in a P2 facility with P3 practices. Samples – We receive blood samples from patients enrolled within our protocol. We also have access to the NIH blood blank for normal human blood samples. As provided by Quentin Sattentau: “Oxford University is states, held in high international regard for its strong teaching and research background and its unique and personal teaching style. Within the University the daughter summary Department of states imported, 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 Chimpanzee Culture, a college advisor. States Imported. The supervisor(s) will generally meet with the student multiple times a term, and a whisper of aids, each of the non-supervisory mentors will meet with the candidate approximately once a term and imported, will file reports on Chimpanzee Culture Essay the candidate’s progress. The candidate will be expected to attend a series of high profile external seminars that take place once a week in term time, and a regular series of internal seminars from leading and more junior University and Departmental investigators and students. Adjoa will attend and united imported oil, participate in social, 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 united imported, other members of the department during tea lunch and coffee breaks, a longstanding Oxford institution! The Department has a fully equipped quiet library for corporate social responsibility policy template 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 united states imported oil, 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 mary, scientific support. We also have strong connections with the biochemistry and chemistry departments and states imported oil, the Weatherall Institute of Molecular Medicine at the John Radcliffe Hospital for obtaining clinical samples and expertise.”

BD FACSAria IIu. BD Pathways 855. VICTOR Light luminescence plate reader. AutoMACS Pro Separator. AutoMACS Classic Separator. Containment II/III Laboratory with 4 tissue culture hoods. Tissue culture. The laboratory has a new tissue culture facility comprised of 8 double hoods and associated incubators and ancillary equipment that is shared with three other virology groups. Virology. Culture Essay. The department has a large, fully-equipped containment-III laboratory shared between two groups, with three tissue culture hoods and associated incubators and united, ancillary equipment, in Understanding Culture, which HIV-1 is grown and used to united states imported, infect cells.

Flow cytometry. The department has a core flow cytometry facility with three BD analyzers (2 x FACScalibur 2 x LSR2) and mary fisher of aids, two sorters. Molecular biology. The Sattentau laboratory has all facilities for molecular biology carried out under containment levels –I, -II and –III. Light microscopy. States. The department has 5 confocal microscopes of varying sophistication and resolution, two of which are set up for live cell immunofluorescence work. The department has three recently acquired high-speed CCD cameras and associated microscopes for live cell immunofluorescence analysis.

The Sattentau laboratory has a Zeiss Pascal confocal microscope and a new CCD camera set up with a Zeiss Axiovert 200 microscope for fixed and live cell work in the containment-III laboratory, allowing real time analysis of live, infected cells. Electron microscopy. The department has two transmission electron microscopes and a scanning electron microscope, all of year boston happen, which are maintained and united, run as a central service facility by the horse a skilled dedicated operator. United States Imported Oil. Our collaborator in Oxford (Kay Grunewald) is located at Change Essay, the University Churchill campus, which is 4 miles from the Pathology Department. He maintains and uses 3 microscopes set up for cryo-tomography as follows. 300keV FEG cryo-electron microscope FEI TF30 Helium Polara with GIF2002 imaging filter (2 x 2k CCD) 300keV FEG cryo-electron microscope FEI TF30 with 4 x 4kCCD 120keV cryo-electron microscope FEI T12 with 4 x 4k CCD. Research Related Senior/Key Person Profile.

[Our Web version of this sample application can't reproduce the layout of the actual PDF forms. See below for united states imported oil the biographical sketch attachments.] My interest in studying infectious diseases stems from the 2001 anthrax scare in the Washington D.C. Climate Change (CO2) Essay. area. I already had a strong interest in science but through my participation in united states, the Gene Search Science Project at did the happen, Catholic University the following summer I came to united oil, 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 Climate Dioxide example, 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. United States Oil. William Winters at Howard University Hospital. Mary Fisher Of Aids. This experience taught me how research and imported oil, medicine are intertwined and inspired me to become a physicianscientist. At UMBC I was a member of the Meyerhoff Scholars Program and an HHMI Undergraduate Research Scholar where numerous lab experiences, seminars, rigorous classes, and multiple opportunities for corporate social responsibility policy 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 imported oil, Michael Summers’ lab. Lawrence Ross: The Hero Of The. Not only united states imported oil 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 Climate Change and Carbon (CO2) excellent research and the internal drive that keeps one focused. United Oil. Working with Dr. Nikola Pavletich I learned the value of immediately organizing my data so that others could analyze my results quickly. In the lab of Tom Cech I had the responsibility of Lawrence Ross: Hero Great of Texas, designing a new protocol to study telomerase assembly, a skill that has enabled me to design a novel assay to united imported oil, investigate AIDS specific questions in my graduate studies. The medical education I’ve received at Columbia has given me a unique perspective with which I approach scientific questions. Under the tutelage of Mark Connors and Quentin Sattentau, leaders in their fields on nonprogressive HIV infection and viral transmission, my understanding of infectious disease and my capacity to pursue further research in these fields will be greatly enhanced. In addition, the courses, medical preceptorships, presentations, teaching, and career development activities I am undertaking in the forthcoming years make me an excellent P.I. for this grant. Academic and Professional Honors. 2003 National Urban League Scholarship 2003 UMBC Meyerhoff Scholar 2003 UMBC Honors College 2003 HHMI Undergraduate Research Scholar 2004 NAD Distinguished Youth Award 2005 UMBC Minority Access to Research Careers Scholar 2005 Abby Rockefeller Mauze Award Charitable Trust Scholar for Dioxide (CO2) Essay example 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 imported oil, the nucleocapsid protein of Moloney murine leukemia virus. Change Dioxide Example. Biochemistry. United States Imported Oil. 44(10), 3735-3744. Year Massacre Happen. 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 united imported, 2,3-diphosphoglycerate in Erythrocytes. Poster presentation at ERHS Science Fair and did the massacre, Prince Georges County Science Fair. March 2003. Smalls-Mantey A, Dey, A, Phillip C, Summers MF. 2004. United Oil. Characterization of High-Affinity Nucleocapsid Protein Binding Sites Within the Moloney Murine Leukemia Virus RNA Packaging Signal.

Poster presented at 2004 Annual Biomedical Research Conference for Minority Students, November 2004. Smalls-Mantey A, Min J, Pavletich N. 2005. Structural and Biochemical Studies of the Yeast Rad4-Rad23 Complex Bound to mary fisher, DNA. Poster presented at Tri-Institutional Gateways to the Laboratory Program Symposium and imported oil, 2005 Leadership Alliance. August 2005. Smalls-Mantey A, Miyazaki Y, Summers MF. 2007.

Dimerization of corporate social, Moloney Murine Leukemia Virus Nucleocapsid Protein Binding Sites Facilitates Binding. Poster presented at united states imported, 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. Fisher A Whisper. 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 united states imported oil, 2010 NIH/Oxford/Cambridge Scholars Research Colloquium. Smalls-Mantey A, Klein R, Doria-Rose N, Laub L, Rood J, Migueles S, Sattenatu. Responsibility. 2010. HIV-Specific Antibodies Mediate Rapid Antibody-Dependent Cellular Cytotoxicity Against Primary HIV-Infected CD4+ T Cells. Poster presented at 2010 International AIDS Vaccine Conference.

September 2010. Smalls-Mantey A. 2010. Antibody-Dependent Cellular Cytotoxicity and the Control of HIV. Talk given at Frontiers in united imported, Biomedicine NIH/Oxford/Cambridge Scholars Program student presentation series. November 2010. [Outside research support redacted from sample.] A. Mary Fisher A Whisper Of Aids. Personal Statement Regarding Project. Currently HIV-specific ADCC is considered one of the very top priorities in the field of HIV-specific immunity.

Our laboratory has assembled the best techniques and 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 united states oil, Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD October 1989 - June 1993 U.S. Public Health Service, Research Associate (C.O.), Respiratory Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD July 1993 - June 1994 U.S. What Year Did The Boston. Public Health Service, Clinical Associate, Clinical Center, National Institute of Allergy and Infectious Diseases, National Institutes of united states imported oil, 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 Understanding Chimpanzee Culture Essay, Infectious Diseases, Clinical and Molecular Retrovirology Section, Laboratory of Immunoregulation, National Institutes of Health, Bethesda, MD December 2007- Present Chief, HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. Recent Honors and Editorial and Review Board Activities.

2009 - U.S. Public Health Service Outstanding Service Medal 2009 - present Vaccine Production Development Team Scientific Advisory Board, University of united oil, Pennsylvania 2009 - present HIV Enterprise Host Genetics and HIV Diversity Working Group 2010 - present Editorial Board, Journal of Virology. C. Peer-Reviewed Publications. Migueles SA, Sabbaghian MS, Shupert WL, Bettinotti MP, Marincola FM, Schwartz D, Sullivan J, and Connors M. HLA B*5701 is Sullivan Ross: The Hero Essay, highly associated with restriction of virus replication in a subgroup of HIV infected long term nonprogressors. PNAS 2000; 97(6): 2709-2714. Migueles SA, Laborico AC, Shupert WL, Sabbaghian MS, Rabin R, Hallahan C, Van Baarle D, Kostense S, Miedema F, McLaughlin M, Ehler L, Metcalf J, Liu S, and Connors M. HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors. Nature Immunol 2002; 3(11); 1061-1068.

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 united imported oil, HLA B*5701+ long-term nonprogressors and progressors to restrict HIV replication is not caused by loss of recognition of autologous viral gag sequences. J Virol 2003; 77(12); 6889-6898. Iyasere C, Tilton JC, Johnson AJ, Younes S, Yassine-Diab B, Sekaly RP, Kwok WW, Migueles SA, Laborico AC, Shupert WL, Hallahan CW, Davey RT Jr., Dybul M, Vogel S, Metcalf J, and Hero of the Great State, Connors M. United States Imported Oil. 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. The Horse Dealer's Summary. Tilton JC, Luskin MR, Johnson AJ, Manion M, Hallahan CW, Metcalf JA, McLaughlin M, Davey RT Jr., and united imported oil, Connors M. Changes in paracrine IL-2 requirement, CCR7 expression, frequency, and year happen, cytokine secretion, of imported oil, HIV-specific CD4+ T cells are a consequence of antigen load. J Virol 2007; 81;2713-2725.

Migueles SA, Osborne CM, Royce C, Compton AA, Joshi RP, Weeks KA, Rood JE, Berkley AM, Sacha JB, Cogliano-Shutta NA, Lloyd M, Roby G, Kwan R, McLaughlin M, Stallings S, Rehm C, O’Shea MA, Mican J, Packard B, Komoriya A, Palmer S, Wiegand AP, Maldarelli F, Coffin JM, Mellors JW, Hallahan CW, Follman DA and Connors M. Lytic Granule Loading of CD8+ T-Cells is Required for HIV-Infected Cell Elimination Associated with Immune Control. Immunity 2008; 29 (6): 1009-1021. Migueles SA, Weeks KA, Nou E, Berkley AM, Rood JE, Osborne CM, Hallahan CW, Cogliano-Shutta NA, Metcalf JA, McLaughlin M, Kwan R, Mican JM, Davey RT Jr, Connors M. Defective human immunodeficiency virus-specific CD8+ T-cell polyfunctionality, proliferation, and cytotoxicity are not restored by antiretroviral therapy. J Virol 2009 83(22): 11876-11889. Doria-Rose NA, Klein R, Daniels M, O'Dell S, Nason M, Lapedes A, Bhattacharya T, Migueles S, Wyatt RT, Korber BT, Mascola JR, Connors M. Breadth of HIV-Specific neutralizing activity in sera: clustering analysis and association with clinical variables. J Virol 2009 84(3): 1631-1636.

Doria-Rose NA and mary a whisper of aids, Connors M. States. 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 Change Dioxide (CO2) Essay, HIV. JAMA 2010 304:194-201. Imported Oil. [Redacted publication in press] The research direction of the HIV-Specific Immunity Section of the Laboratory of Immunoregulation is focused upon mechanisms of immunity to HIV. Social Policy. The laboratory is states imported oil, staffed by PhD and MD scientists with extensive experience in the humoral or cellular immune response to and Carbon Essay example, HIV. In addition we have close collaborations with investigators at states oil, the NIAID Vaccine Research Center in the area of structure-function relationships of HIV-specific antibodies.

Our laboratory is well equipped with multi-laser flow cytometers, automated magnetic sorters, and imaging equipment to carry out boston massacre, this project. Our laboratory is supported by the research budget of the Division of united states imported, Intramural Research. Corporate Social Template. 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 states imported the humoral response to Essay, HIV. Positions and Employment.

1985 - 1992 Lecturer, Department of Genito-Urinary Medicine, University College London, UK 1989 - 1991 Visiting scientist, Howard Hughes Medical Institute, Columbia University, New York, NY 1992 - 1998 Staff scientist (Director of Research), Centre d’Immunologie, Marseille, France 1999 - 2003 Reader, Section of Infectious Disease, Imperial College London, London UK 2003 - Professor of immunology, Department of states imported, Pathology, University of Oxford, Oxford UK. Other Experience and Dioxide (CO2), Professional Memberships. 1995 - Member, American Association for the Advancement of Science 1998 - Member, American Society for Microbiology 1998 - Member, British Society for Immunology, UK 1998 - Member, Society for General Microbiology, UK 2005 - Member of the united states imported Pasteur Institute Paris France Scientific Evaluation Committee. The Horse Dealer's Daughter Summary. 2005 - Member of the united imported Vaccine Research Center (VRC) NIH Board of Scientific Councilors 2007 - Member of BMGF Vaccine Monitoring Centre SAB 2008 - Member of year did the boston, NIH HIVRAD/Novartis Neutralizing Antibody Vaccine Consortium SAB 2009 - Member of study section for Swedish Program for International Development 2010 - Member of NIH study section for the B cell Immunology Partnership Program for HIV-1 Vaccine Discovery (U19) C. Selected Peer-Reviewed Publications. Most relevant to the current application.

Martin N, Welsch S, Jolly C, Briggs JA, Vaux D and Sattentau QJ. (2010) Virological synapse-mediated spread of human immunodeficiency virus type-1 between T cells is sensitive to entry inhibition. J. Virol. 84: 3516-3527. Gonzalez N, Bermejo M, Calonge E, Jolly C, Arenzana-Seisdedos F, Pablos JL, Sattentau QJ and Alcami J. (2010) SDF-1/CXCL12 production by united states oil mature dendritic cells inhibits the propagation of X4-tropic HIV-1 isolates at the dendritic cell-T-cell infectious synapse. J Virol. 84:4341-51 Groot F, Welsch S and Sattentau QJ. Social Responsibility Template. (2008). Efficient HIV-1 transmission from macrophages to T cells across transient virological synapses. United States Imported. Blood 111: 4660-4663. Sowinski S, Jolly CJ, Berninghausen O, Purbhoo, MA, Chauveau A, Kohler K, Oddos S, Eissmann P, Brodsky FM, Hopkins C, Onfelt B, Sattentau QJ and Davis DM (2008). Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission.

Nature Cell. Biol. Of Aids. 10: 211-219. Jolly C and Sattentau QJ (2007). HIV-1 assembly, budding and cell-cell spread in T cells takes place in tetraspanin-enriched plasma membrane. J. Virol.

81:7873-7884 Jolly C and Sattentau QJ (2007). Adhesion molecule interactions facilitate human immunodeficiency virus type-1-induced virological synapse formation between T cells. J. Virol. 81: 13916-13921. Jolly C, Mitar I and oil, Sattentau QJ (2007).

Requirement for an intact actin and tubulin cytoskeleton for efficient HIV-1 assembly and spread. What Year Did The Massacre. J. Virol. 81: 5547-6 Jolly C and Sattentau QJ. Human Immunodeficiency virus type-1 virological synapse formation in T cells requires lipid raft integrity. J. United States. Virol.

2005 79: 12088-12094. Jolly C, Kashefi K, Hollinshead M and Sattentau QJ (2004) HIV-1 cell-to-cell transfer across an Env-induced, actin-dependent synapse. J. Exp Med. 199: 283-193. Additional recent publications of important to the Field (in chronological order)

Wegmann F, Krashias G, Luhn K, Laamanen K, Vieira S, Jeffs SA, Shattock RJ and Sattentau QJ (2011) A novel strategy for Understanding Chimpanzee Culture Essay inducing enhanced mucosal HIV-1 antibody responses in an anti-inflammatory environment. PlosOne 6: e15861. Kong L, Sheppard N, Stewart-Jones G, Robson CL, Chen H, Xu X, Krashias G, Bonomelli C, Scanlan CN, Kwong PD, Jeffs SA, Jones IM, Sattentau QJ (2010) Expression system-dependent modulation of HIV-1 envelope glycoprotein antigenicity and immunogenicity. United States Imported. J. Mol. The Horse. Biol. Aug 25th epub. Krashias G, Simon K, Wegmann F, Kok WL, Ho LP, Stevens D, Skehel J, Heeney JL, Moghaddam AE and Sattentau QJ. (2010). Potent adaptive immune responses induced against HIV-1 gp140 and united states oil, influenza virus HA by a polyanionic carbomer.

Vaccine 28: 2482-2489. Zanetti G, Briggs JAG, Grunewald K, Sattentau QJ and Fuller SD. SIV spike glycoprotein structure in situ determined by cryo-electron tomography. Plos Pathogens August 2 (8): e83 Sheppard NC, Bates AC and Sattentau QJ (2007). A functional human IgM response to HIV-1 Env after immunization with NYVAC-HIV C. AIDS 19: 524-527. [Outside research support redacted from sample.] PHS Fellowship Supplemental Form, Research Plan. [Our Web version of daughter, this sample application can't reproduce the layout of the actual PDF forms. United States Imported Oil. The attachments are included below. What Boston Massacre Happen. 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 united oil, the search for dealer's effective vaccines or immunotherapies for HIV.

Antibodies (Abs) induced by candidate vaccines to the surface envelope glycoprotein have not neutralized a broad array of primary virus isolates. For this reason, eliciting a cytotoxic cellular response has been the primary goal in most recent vaccine trials. However, this approach has not been successful in containing viral replication in vaccinees that have become HIV-infected. Antibody-dependant cellular cytotoxicity (ADCC) has been shown to mediate sterilizing immunity against challenge with pathogenic simian immunodeficiency virus [Hessel 2007]. In ADCC, Fc-bearing Abs bind viral epitopes coating an infected CD4+ target T cell and an Fc receptor bearing effector, most commonly natural killer cells (NKs), bind the Ab and united imported, use perforin to deliver granzymes which induce apoptosis in Understanding Chimpanzee Essay, the target. We want to study ADCC in infected patients to understand the magnitude and characteristics of the best responses achieved by natural infection.

First, we will compare ADCC mediated by the sera of a cohort of patients using a granzyme B cytotoxicity assay developed in our lab. States Oil. Based on these findings, we will select the the horse daughter sera of united, patients with the corporate responsibility policy most ADCC, generate monoclonal Abs (mAbs), and characterize the mAbs based on epitope specificity, affinity, potency, breadth, IgG isotype, and Fc type. We will also evaluate whether ADCC is disparate from classical neutralization. Finally we will use microscopy to states, examine the year happen synapse between effectors, Abs, and targets. The outcome of states imported, this research will provide insight into the characteristics of Abs that mediate ADCC that are likely important goals in the design of daughter, HIV vaccines or immunotherapies.

Hypothesis: Antibody-dependent cellular cytotoxicity (ADCC) is united states imported oil, 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 Ross: The Hero of the Great State of Texas Essay, subclass of HIV-specific antibodies. Aim 1 : Characterize the potency of sera of HIV-infected individuals in ADCC. In ADCC, Abs bind viral epitopes that are presented by infected CD4+ T cells. NKs expressing an united states imported oil Fc receptor bind the Fc domain of the Ab and use perforin to deliver granzymes to the HIV-infected cell. Year Did The Boston Massacre Happen. 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 imported oil the percent of target cells receiving granzyme and the elimination of targets as defined by residual percent of targets expressing p24, HIV capsid. Compare the serum of HIV+ individuals with various rates of Climate Dioxide (CO2) Essay example, progression and viral loads to determine which contain Abs capable of mediating the highest levels of ADCC. Compare the united imported oil ADCC and neutralizing activity of patient sera. Aim 2 : Characterize the specificity and breadth of antibodies with ADCC activity.

Our laboratory has panels of NAbs derived from patients with known serum neutralizing or ADCC-mediating activity. Determine whether recognition of what year did the happen, specific epitopes is required for ADCC. Define the breadth of the polyclonal sera by its ability to mediate ADCC in CD4+ T cells infected by united states oil different clades of HIV. Change. Titer serum total IgG, IgG1, and IgG3 binding infected CD4+ T cells. Aim 3 : Characterize the imported oil structure and corporate, 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 united imported, tomography, we will examine the synapse formed between NK and other cells with potential ADCC activity (macrophages and neutrophils) and Understanding Culture Essay, infected target cells.

We will specifically investigate: The structure of a functional ADCC synapse. The kinetics of ADCC function in real time and united states imported oil, its relation to antibody type and specificity. A role for antibody-dependent cell-mediated phagocytosis (ADCP) in daughter, elimination of HIV-infected cells. d. Receptors and effector molecules central to ADCC activity against HIV infected cells. Since being identified as the causative agent of AIDS in 1983, HIV infection has reached epidemic proportions with an estimated 2 million people worldwide dying from AIDS each year 1- 3. There is more public awareness about how to prevent HIV infection but with the growing incidence of HIV infection and 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 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 united, a much earlier point in development with smaller numbers of participants. Over the past 20 years, research into correlates of immunity to did the, HIV have largely focused on CD8+ cytotoxic T lymphocytes (CTLs) or neutralizing antibodies (NAbs). In addition to neutralization, antibodies (Abs) may fight viral infections by antibody-dependent cell-mediated phagocytosis (ADCP) or by antibody-dependent cellular cytotoxicity (ADCC). In ADCC, Abs bind viral epitopes presented on states oil infected target cells and Fc? receptor-bearing effector cells such as natural killer cells (NKs) recognize and bind the Fc? region of these Abs. Upon cross-linking of the Fc? receptor, NKs release perforin that punctures the target’s cell membrane and deliver proteases such as granzyme B (GrB) which induce apoptosis. ADCC has become a major focus within the 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 a whisper of aids, protecting macaques from HIV whereas Abs with impaired complement binding conferred protection to macaques, suggesting that ADCC may be more important in preventing infection than neutralization or complement activation alone 4. 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 states imported oil, vivo.

In addition, some recent data in human efficacy trials has also greatly increased interest in ADCC as an important component of vaccine induced immunity to HIV. In September 2009 data from the phase III RV144 (Thai) vaccine trial were released and showed that the prime-boost combination of ALVACR HIV and AIDSVAXR B/E reduced HIV infection. This vaccine regimen was known to mary fisher, not elicit a strong cellular or NAb response. It does, however, elicit binding antibodies that have suggested to the field that the protective efficacy is likely mediated through ADCC 5. Our laboratory is united states, part of a large international effort to Understanding Culture, characterize ADCC antibodies from this trial in order to determine whether there were higher ADCC-mediating antibodies in united imported, uninfected vaccinees compared to those that were infected. Although HIV-specific ADCC is now considered an extremely important part of vaccineinduced immunity several basic questions regarding the Lawrence Hero Great State of Texas nature of an united imported effective ADCC response have not been addressed. Lawrence Sullivan Hero Of The Great Of Texas. For example, the number, affinity, and united states, specificities of Understanding Chimpanzee Culture Essay, antibodies necessary to mediate ADCC remains poorly understood. Our laboratory has now developed assays that can accurately measure ADCC against HIV-infected cells. We also have assembled panels of monoclonal antibodies from individual patients that permit a characterization of individual antibodies that mediate HIV-specific ADCC. One of the initial goals of this project was to adapt our current killing assay to united oil, provide a more robust assay for HIV-specific ADCC. Past studies of ADCC have been hampered by the availability of assays that are only Lawrence Ross: State of Texas partially quantitative.

There are four primary methods that people use to measure ADCC 6. States Oil. The most prevalent is the chromium release assays (CRA), which is highly variable, does not specifically account for the mechanism of Understanding Chimpanzee, killing, and is insufficiently quantitative 7. The ADCVI assay incubates targets, serum, and imported oil, effectors for 24 hours and Climate Essay, the supernatant is applied to states imported oil, the B95-8 cell line for 5-7 days. The endpoint is reduction of viral infection of the Understanding Culture Essay 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 imported, infected cells. Another assay is the happen intracellular cytokine staining ADCC (ICS-ADCC) assay measures IFN-?, the primary cytokine responsible for united imported the antiviral activity of many cells including NKs, CTLs, Th1, and dendritic cells 9. Dioxide (CO2). The advantages of oil, this assay are that multiple effector functions can be measured and all cells and Abs are from the Change Dioxide (CO2) Essay example same patient, but it is still a proxy that does not measure HIV-infected cell killing. The rapid and fluorometric antibody-dependent cellular cytotoxicity (RFADCC) assay directly measures cell killing but requires whole protein 10. While use of protein pulsed targets is a sensitive method, it likely places artificially high amounts of imported, protein on corporate social 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 united states oil cytotoxic activity of CTLs developed in our lab11. This assay measures the cleavage of a GrB substrate, and eliminates background cell death using a Live/Dead stain to produce accurate quantitative and highly reproducible results. In brief, CD4+ T cells are stimulated for 3 days and HIV infected.

Autologous, negatively selected NKs are used as effectors. Effectors and targets are labeled with surface dyes so that they can be discriminated. NKs, targets and serum are incubated in Chimpanzee Essay, the presence of united imported, a granzyme cleavable fluorescent substrate. Granzyme delivery to the target cell and elimination of Understanding Chimpanzee Culture, HIV-infected targets can then be measured by flow cytometry (Figure 1). Cellular GrB content.

GrB cleaves GranToxiLux substrate (FITC), indicating the amount of GrB present within a target cell (Pacific Blue). Elimination of HIVSF162-infected cells. Live targets are stained for intracellular HIV capsid, p24 (PE). Some infected cells show downregulation of CD4 (PE-Cy7). A reduction in the number of p24 stained cells is represented as Infected Cell Elimination (ICE) and 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 states, this assay over older assays that use mismatched cell lines. Because NKs lyse target cells in the context of Understanding Essay, MHC mismatch and cause nonspecific killing, autologous cells are used in our assay to reduce background. Imported Oil. 12. In addition, because NK function is diminished in HIV-infected patients, we use the fisher a whisper 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 states oil, mediating ADCC 13, 14. We observed variations in NKs from normal individuals in a whisper, their ability to mediate ADCC and choose donors that provide optimal signal to noise ratio that we will use to compare the serum of HIV+ individuals (Figure 2). The targets used in this assay are likely closer to the in united states, vivo situation given autologous HIV-infected targets are used in the place of Climate Change and Carbon Essay example, antigen pulsed cell lines. Other advantages include our assay’s ability to measure the united oil mechanism of Lawrence The Great of Texas, ADCC (granzyme delivery) and the outcome (death of infected cells) (Figure 2). MHC-1 is down-regulated in virally infected cells, and united imported, the loss of MHC-mediated killer inhibitory signals permit NKs to kill a cell 15, 16. We control for this by measuring the Lawrence Sullivan Ross: The of the State Essay granzyme content of targets that are incubated only with effectors and imported oil, sera from HIV-uninfected volunteers. Culture. 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 (3) GrB delivery is proportional to cell death.

Aim 1: Characterize the magnitude of ADCC in HIV infected individuals . Rational : There is considerable controversy regarding the united oil magnitude of ADCC activity in sera from HIV+ individuals and how it correlates with disease progression. It has been suggested that sera from the horse dealer's elite controllers exhibit greater ADCC activity which correlates with CD4+ T cell count 17, 18 while others have sighted no correlation between ADCC and states imported oil, disease progression 19, 20.We will compare the Understanding Essay serum of HIV+ individuals with various rates of progression and united, viral loads to determine which contain Abs capable of mary, mediating the highest levels of ADCC. We will also compare the ADCC and neutralizing activity of patient serum to united states imported, evaluate whether or not ADCC and neutralization always occur together in Ross: Hero of the Great State Essay, polyclonal sera which is yet to be determined 21, 22. Methods : Over the past several years, in collaboration with the Vaccine Research Center (VRC) our laboratory has focused upon recruiting HIV-infected patients with broadly crossneutralizing antibodies. We have extensive clinical data and neutralization data for all of the patients. With the data we generate from our ADCC assay we are able to compare multiple indicators of united states oil, immunity with ADCC.

Expected Outcomes/Interpretation : Based on in vitro and Lawrence The Hero State of Texas Essay, passive transfer macaque studies, we expect LTNPs to exhibit greater ADCC than progressors. Our current knowledge attributes LTNP delayed progression to superior CTL cytotoxicity but our data may show ADCC also to be a significant factor 11. Potential Complications : We do not foresee any difficulties in united, accomplishing this objective. Aim 2: Characterize MAb from serum identified as having potent ADCC activity with regard to Climate and Carbon Dioxide Essay, specificity. Rational/Methods : HIV-infected cells express Envelope (Env) protein on their surface which is recognized by NAbs and presumably by ADCC-mediating Abs. We will use standard Nabs (including b12, 2F5, 2G12, 447-52D, 17B, and VRC01) and patient derived MAbs to probe specificities required for ADCC. An ideal HIV vaccine would be able to protect against diverse virus strains so it is important to determine whether Abs raised against imported, one clade of virus would be able to mediate ADCC in what did the massacre, CD4+ T cells infected by united oil different clades. We will use multiple strains of virus from clade A/E, B, and C to infect CD+ T cells and compare killing of target cells in the presence of serum pooled from clade B HIV+ patients. IgG1 and fisher a whisper, IgG3 are the predominant IgG isotypes with roles in imported oil, ADCC. Sullivan Of The Great Essay. It is possible that variations in ADCC activity of states imported, sera are mediated by what year massacre happen variations in IgG subclass. We will use infected CD4+ T cells, apply sera with various levels ADCC at united states, the same dilutions used in Change example, our killing assay, and measure total bound IgG, IgG1, and IgG3 by united imported flow cytometry.

We believe flow cytometry is a better way of measuring titers of binding Abs as compared to mary fisher of aids, ELISA because Abs will recognize all possible epitopes on the surface of an infected cell in their natural conformation. Expected Outcomes/Interpretation : Determining the association between ADCC activity and IgG subclass may provide insights into united states imported oil, the necessity of Chimpanzee Culture Essay, eliciting a specific class of IgG via particular antigens and adjuvants. Potential Complications : We now have robust assays for subclass binding and do not expect complications with this portion of the project. Aim 3: Evaluation of the target-effector synapse. Rational : Using microscopy to study ADCC is important because it will help us define structural and states oil, kinetic parameters and will relate structure to function.

Multiple mechanisms for cell-to-cell spread of HIV have been described but few have described inhibition of viral transmission or targeted cell death 23. To date there has been no study using microscopy to investigate ADCC in HIV using NKs or macrophages as effectors and CD4+ T cells as targets. In 1994 one group designed a bispecific antibody with anti-CD4 and anti CD3 heavy chains that would redirect CD8+ T cells to kill HIV infected targets 24. With fluorescent microscopy they observed after 1 hour of mary of aids, incubation that 24% targets had formed conjugates with CD8+ T cells although many more cells had lysed. At 2 hours 50 - 80% of targets were conjugated and undergoing lysis and by 24 hours all targets had been lysed. However, the imported bispecific antibody may not be representative of ADCC with naturally occurring HIV-specific antibodies. In addition, the Lawrence Sullivan Ross: of the Great State of Texas Essay structure of the NK to HIV-infected target synapse was not examined.

Methods : The lab of Quentin Sattentau has focused on examining the synapse of cells involved in HIV infection. United States Oil. 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. Change And Carbon Essay Example. They have recently demonstrated that macrophages can infect CD4+ T cells every 6 hours and that cell-tocell transfer of virus is 10-fold more efficient than free virus spread 26. To study the kinetics of ADCC in real time we will use time-lapse laser scanning confocal microscopy (time-lapse LSCM). United Oil. 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 NKs to evaluate ADCC; or neutrophils/monocytes to evaluate antibody-dependent cell-mediated phagocytosis (ADCP) and applied to poly-L-lysine coated cover slips. Corporate Responsibility Policy. Cover slips will be fixed in paraformaldehyde, quenched with NH4Cl, permeabilized with Triton-X, and stained for united states 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 Culture Essay, tomography (TEM) to states imported, generate higher resolution static images of the ADCC functional synapse.

For TEM targets, serum, and effectors will be incubated for Change Dioxide example approximately 1 hour, fixed in paraformaldehyde and glutaraldehyde, and stained with osmium tetroxide. Samples will be embedded in epoxy resin, cut, and imaged using a 300kV FEI Technai TF30 27. If necessary cryo-EM will also be used for structural studies with the aid of Oxford collaborator Kay Grunewald. These experiments will be completed using the pathology department’s core bioimaging facility and I will take department’s Advanced Light Microscopy and Electron Microscopy course in preparation for this research. Expected Outcomes : We expect to states imported oil, elucidate the kinetic and the horse dealer's daughter, 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. States Imported. 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 Lawrence Sullivan Ross: of the State Essay, ADCC with potential utility for HIV vaccine trials; and states, increased understanding of basic HIV immunology. In the wake of the RV144 trial, ADCC has become a major focus in the field of HIV-specific immunity. We are very well positioned to carry out these important studies because of our large collection of cells, sera, and detailed clinical data from patients that are part of the NIAID HIV clinic, and both labs’ extensive experience in this area. Samples are collected under the NIAID IRB-approved protocol 02-I-0086. Understanding Culture. Protections for human subjects are in united states, accordance with NIAID Division of Intramural Research policies.

Phlebotomy may cause some discomfort, and occasionally some bleeding or bruising at the site. On rare occasions, people faint while having blood drawn. Blood drawing will not exceed 150 milliliters (30 teaspoonfuls) on Understanding 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 states imported safety guidelines for blood drawing practiced at the Clinical Center. Like standard phlebotomy, leukapheresis is occasionally associated with local bleeding and bruising at dealer's daughter, the site of needle insertion. Lightheadedness can also occur, and people faint on states imported rare occasions. Occasional tingling in the arms and legs can occur with the procedure and fisher a whisper, can usually be relieved by chewing a calcium-rich tablet that the staff will provide. In addition, on very rare occasions (less than 1 in every 1,000 times), malfunction of the leukapheresis machine can result in blood loss of states, up to 450 milliliters. Lawrence Ross: Of Texas Essay. Trained medical personnel who are equipped to deal with any of these potential problems will always be on hand during the procedure. Inclusion of Women and Minorities. Gender, Ethnicity and Race Consideration.

This study involves techniques and procedures that are currently approved for various indications. Male and female adult patients (18 years of age or older) will be enrolled without preference to gender, race or ethnicity from the oil pool of patients that receive care in Clinics 8 at the horse daughter summary, the NIH Clinical Center. Patients will be recruited from outside the NIH community by advertisements posted in states, the Clinical Center, the NIAID web site, and social policy template, advertised in other media. We will attempt to united states, 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 Climate Change and Carbon (CO2) Essay, interrupt HAART, patients will be fully counseled prior to entry into the study as to united, the potential risks of discontinuing HAART therapy and the potential benefits of continuing HAART therapy, in the setting of a documented virologic and/or immunologic response. Patients who do not fully comprehend these potential risks of HAART cessation, in the opinion of the study team, will not be offered participation in the study.

Patients stopping HAART therapy will be monitored closely for the horse daughter summary virologic and immunologic relapse and will be offered therapy, based upon united imported oil, the algorithm for safety outlined above. Target enrollment for this study is mary fisher of aids, 300 individuals and is currently ongoing. Inclusion of Children (and Pregnant Women) Inclusion of Children and Pregnant Women. This study will be confined to HIV-infected adults greater than or equal to 18 years of age. As an observational study there is no therapeutic benefit or clinical intervention resulting from participation in united imported, this trial, thereby children are not being denied the potential benefits of the horse daughter summary, a research intervention. We also do not have the historical research database and in vitro findings on imported oil HLA linkages with LTNP in the pediatric population to make valid comparisons within that cohort. The potential risks of withdrawing therapy in minors have not been studied and therefore may present unknown additional risks to that study population. Comparable units specializing in pediatric HIV are available at the NIH to address this topic, should preliminary results from this study warrant further evaluation in the pediatric population.

The safety of discontinuing antiretroviral therapy has not been established during pregnancy and nursing, and current guidelines continue to advise HIV-positive women to did the, take antiretroviral therapy to prevent viral transmission to the child during that time period. United. Therefore, pregnant or nursing women will be excluded from year happen 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. Imported. I initiated contact between the two individuals and they agreed to dealer's daughter, start a collaborative project with me. After studying NAbs with Mark Connors for one summer I decided I wanted to focus on antibodies that mediate ADCC. I outlined the facets of ADCC I wanted to investigate then received feedback from both mentors. I subsequently wrote the proposal that was edited by both mentors and Mark Connors made final revisions. I meet multiple times during the week with Dr. Connors to discuss my research progress and to plan future experiments.

We also conduct quarterly phone conferences with Dr. Sattentau, maintain a regular email correspondence, and states imported oil, meet at conferences. Communication will continue in the same manner while I am in Quentin Sattentau’s lab. Selection of Sponsors and Sullivan State, Institution. Selection of Institution.

I decided to join Columbia’s MSTP program because of states imported, its tradition of exemplary medical education, medical research, and unparalleled support offered to students from Change and Carbon Dioxide (CO2) Essay example program administrators. United. Because of my previous research experience with HIV I knew I wanted to continue research in this field. Change Dioxide Essay. I decided to join the NIH/Oxford/ Cambridge Scholars Program to complete my dissertation research because it would provide me access to a more extensive network of scientists than Columbia could. Oxford has a particularly strong network of HIV investigators and the structure of oil, its graduate program allows for a particularly specialized education. As a graduate student in the pathology department I am allowed to select seminars and accelerated 1-day to 1-week courses that allow me to attain skills quickly and immediately implement them into my research. Ross: The Of The Great. In addition, the NIH/Oxford/Cambridge Scholars program provides funding for students to take courses offered by any institution giving me access to virtually any educational opportunity necessary.

In addition, through NIH’s Foundation for Advanced Education in the Sciences I’ve had the opportunity to take courses that will help me towards my goal as in infectious disease investigator such as the united states imported oil Vaccine Development course I completed. The NIH/Oxford/Cambridge Scholars Program is designed so that students work with a mentor at NIH and one at a university. The Horse Dealer's Daughter Summary. When I joined the program I searched for HIV investigators throughout NIH and Oxford and identified Mark Connors and Quentin Sattentau as potential mentors because I wanted to 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 stimulate systemic and mucosal immunity. Through my search at the NIH I identified Mark Connors as a potential collaborator though he and Quentin had never collaborated before. I believed Dr. Connors’s expertise in NAbs of long-term nonprogressors (LTNPs) would complement Dr. Sattentau’s vaccine development goals. In addition, Dr. Connors’s unique cohort of states imported, LTNPs would provide ready access to samples to study many facets of HIV infection. Finally, I believe Dr.

Sattentau’s approach to research as a PhD and Dr. Connors’ as an MD will teach me to think about science in a more practical way that is suited to me as a future MD/PhD researcher. I will follow the principles on responsible conduct of research as outlined in NOT-OD-10- 019. As an undergraduate at UMBC I took a semester-long course entitled “Ethics/Integrity in Chimpanzee Culture Essay, Scientific Research” which first help me to understand the responsibility scientists have to one another and medical community honestly share information. States Imported. As a Columbia medical student, I have taken the Hippocratic Oath to guide my patient care and I am expected to Climate Essay, adhere to the code of ethics as outlined in states imported, 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 Climate Dioxide example, essential that I maintain the confidentiality of these individuals. When I started research at NIH I participated in a patient confidentiality seminar.

Oxford offers an “Ethics: Confidentiality” course in united states imported oil, which I will enroll to better my further my understanding and ability to Understanding Chimpanzee Culture, maintain ethical practices with regards to research. As a physician, I hope to alleviate an individual’s immediate suffering; and as a scientist I hope to contribute to long-term solutions that can prevent suffering. To work most effectively at the interface of medicine and imported oil, science, I have endeavored to what year boston, earn an MD/PhD. I believe that the united states oil combined degree’s greatest value lies in the perspective that it affords: to approach patient care with a researcher’s eye, and to approach research with a physician’s focus on did the massacre improving the quality of life. A few years ago I conducted research on telomerase, an enzyme that maintains healthy chromosome length. States. When telomerase is Chimpanzee Essay, upregulated, as it is in 90% of carcinomas, cells can propagate indefinitely. United Imported Oil. When telomerase levels are halved, a bone-marrow failure disease called Dyskeratosis Congenita (DC) results. While looking at what massacre happen, yeast cells with low levels of telomerase and measuring their growth rates, I noticed two things.

The first was that cells with low levels of telomerase grew slowly. Secondly, these cells had abnormal morphologies, as do tumor cells. These observations led me to wonder whether the progression of cancer in united states, 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. Understanding. A literature search demonstrated a lack of any substantial research concerning this question. Research in biochemistry affords many new advances in medicine, but through that experience the importance of keeping a broader medical picture in mind became clear to me. My goals as a physician scientist are to treat patients and conduct research that will allow me to impact patients I will never meet through therapeutic discovery; specifically serving as a creative link between science and medicine in united imported, the field of mary fisher a whisper, infectious disease. United States Imported Oil. The training I will receive in the horse daughter summary, Oxford’s doctorate program will prepare me to be a competitive investigator through a tailored curriculum, expert dual-mentoring, learning to work in a collaborative environment, and by giving me extensive writing experience via paper submissions and even through this grant. These are all specific skills that would be harder and take longer for states imported oil me to garner through a traditional medical student experience. Did The. The advantage I have in understanding that I want to be a physician-scientist has given me the opportunity to carefully cultivate these skills early in my career.

Activities Planned Under This Award. Research 80%, Seminars/Courses 10%, Presentation/Career Development/Clinical 10% Research Skills : While working in Mark Connors’s lab I have acquired specific skills such to creatively study immunology such as learning to use flow cytometry. I discuss my research progress frequently during the week with Dr. Connors. We also have phone conferences and united imported oil, meet with Dr. Mary Fisher. 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. United States Imported. I also completed a 3-day grant-writing course during my senior year of college. I will improve my writing skills through preparation of manuscripts based on my research to be submitted for publication, applying for training grants, and submission of a report for my transfer viva (qualifying exam).

I will also complete the Scientific Writing from a Reader’s Perspective seminar. Discipline specific learning : I completed the 3-day “Vaccines: Development and 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 opportunity to be mentored by an infectious disease clinician. Presentations : I will continue to annually attend and the horse daughter summary, 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 united imported oil, the Oxford Pathology Graduate Student Symposium. I have given a talk to my graduate program journal club and will have more opportunities to present my research in lab meetings. Career Development : The NIH/Oxford/Cambridge Scholars programs hosts a seminar series where leaders in government/academic research, the pharmaceutical industry, and finance speak with us about their career. I also attended NIAID Fellows retreat that focused on career development. Teaching : As I prepare to leave the lab I will be responsible for policy training a new research fellow. Year 1 (continued) and Year 2: Quentin Sattentau Lab (Oxford) Research 75%, Seminars/Courses 10%, Presentation/Career Development/Clinical 10%, Teaching 5% Research Skills : While working in Quentin Sattentau’s lab I will learn to apply microscopic imaging to studying HIV infection. I will have weekly meetings to discuss my research progress.

We will have phone conferences and meet with Dr. Connors at various conferences throughout the year. I have also been assigned a graduate advisor within the pathology department but not in my specific lab who will help me to objectively evaluate my research. Writing Skills : I will improve my writing skills through preparation of manuscripts based on my research to be submitted for publication and writing reviews. I will complete the imported following 1-day courses offered at Oxford: Writing Skills – Paper and Thesis; Doctoral Thesis Writing, Discipline specific learning : I will participate in courses and Understanding Culture, Skills Workshops offered by Oxford including “Advanced Light Microscopy,” “Electron Microscopy,” and “Introduction to imported, Statistics.”

Bench to bedside clinical training : I will attend the Nuffield Department of Clinical Medicine Grand Rounds and shadow an infectious disease clinician. Career Development : See above. I will also attend the 4-day Oxford GRADschool, a personal development course. Teaching : I will seek to be an undergraduate lab instructor and take the Oxford course “Teaching and Learning Skills” to prepare myself. Year 3 and Year 4: Medical School (Columbia) In the the horse dealer's summer after 11th grade I participated in the intensive 6-week Gene Search Program at the Catholic University of America that introduced me to molecular biology and the exciting race to sequence the human genome. That summer, I learned much more than how to united states oil, run a gel; I learned to read and comprehend primary research articles and how to fisher of aids, design experiments.

Because of my accomplishments that summer, I was invited to united oil, participate in an extension of the Gene Search Program during my 12th grade year. This program inspired me to pursue a career in biomedical research because I began to understand how the 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 Climate Change and Carbon Dioxide Essay example, 2,3- DPG. While this effect may seem advantageous to patients with sickle cell anemia, deoxygenating hemoglobin ultimately causes red blood cells to sickle by promoting hemoglobin polymerization. Previous studies indicated that adenosine might regulate 2,3-DPG levels through an interaction with the A3 receptor. To test this idea, we indirectly measured 2,3-DPG levels by using spectrophotometry to measure a by-product of the 2,3-DPG pathway.

An exciting therapeutic prospect of our research is that an antagonist of the A3 receptor may prevent the accumulation of 2,3-DPG and RBC sickling in patients with sickle cell anemia. I documented this work in united states imported oil, a five-chapter thesis, in accordance with my high school’s Science and corporate social responsibility template, Technology Program, and presented it at states, my school’s science fair, where I was awarded third place in biochemistry. During college I spent four years working with Dr. Understanding Chimpanzee Culture Essay. Michael Summers to investigate Moloney Murine Leukemia Virus (MuLV) dimerization. Understanding dimerization is key to developing gene and antiviral therapies. United States Oil. MuLV is similar to HIV in a whisper of aids, that it is a retrovirus that packages two copies of its RNA genome. Packaging of united states oil, 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. Fisher Of Aids. Previous work in the Summers lab suggested a riboswitch mechanism for MLV genome packaging, where, in monomeric RNA, Psi-site UCUG segments capable of binding NC are sequestered by base pairing, but upon dimerization, become exposed to bind NC.

My project was to investigate whether similar sequences in united imported, the Psi-site could also bind NC. Using isothermal titration calorimetry and Chimpanzee Culture Essay, nuclear magnetic resonance, we identified short RNAs (ACAG, UUUG, and united states imported oil, 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 which three nucleotides lie upstream of the guanosine. The paper I co-authored (Dey, A., et. al., 2005) extends an established model for Climate and Carbon genome recognition, in which the NC domains of assembling Gag molecules interact with multiple X(i-3)-X(i-2)-X(i-1)-G(i) elements (X is a variable nucleotide) that appear to united states oil, be preferentially exposed in the dimeric RNA. I presented this research at the 2004 ABRCMS and at multiple UMBC symposiums.

I continued to investigate potential dimerization and NC-binding regions of the Psi-site using native and mutant MuLV RNA segments in gel-shift assays. As expected from our riboswitch hypothesis, we observed NC binding preferentially to responsibility template, RNA dimers which was also confirmed by equilibrium dialysis. Most recently our lab published the NMR structure of this dimer (Miyazaki, Y., et al., 2010). During the united states oil summer of 2005 I participated in the Weill Cornell/Rockefeller/Sloan Kettering Gateways to the Laboratory Program. I worked with Dr. Nikola Pavletich toward solving the crystal structure of the Sullivan The Hero State Essay Saccharomyces cerevisiae Rad4-Rad23 complex bound to a DNA substrate. Rad4-Rad23 is states oil, a homolog of human XPC-HR23B, a DNA damage-repair protein. In its mutated form, XPC-HR23B causes the disease Xeroderma Pigmentosum. Patients are extremely sensitive to UV-light and develop skin cancer during childhood. I identified DNA substrates to be used in crystallization trials by HPLC-purifying DNA, performing gel-shift assays, and setting up crystal trays.

I presented this work in a talk before the Tri-Institutional community and during posters sessions at the 2005 Leadership Alliance National Conference and at Change and Carbon Essay example, the 2005 SACNAS National Conference. In 2006 I studied telomerase assembly in the lab of Dr. Thomas Cech at the University of Colorado at Boulder. The central role telomerase plays in protecting chromosome integrity places telomerase at the heart of two common human ailments—cancer and aging. To study how and united imported oil, where in the cell telomerase is assembled from its RNA and protein components, we used the budding yeast Saccharomyces cerevisiae as a model organism. Understanding Chimpanzee. We sought to understand whether the noncoding telomerase RNA (TLC1) goes through a cytoplasmic phase during its biogenesis. One model is states imported oil, that a polyadenylated precursor form of corporate social responsibility template, TLC1 is exported to the cytoplasm where it associates with Sm proteins. Mtr10p then plays a role in importing the TLC1-Sm complex back into the nucleus, where the 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 united imported, Mark Connors where I screened patient sera for dealer's daughter breadth and potency of neutralizing Abs against HIV using a TZMBL neutralization assay. We demonstrated that that progressor serum has greater breadth in potency in neutralizing HIV than Long-Term Nonprogressors (Doria- Rose, N., et al., 2009). Studying NAbs peaked my interested in other anti-viral mechanisms mediated Abs and lead to my proposed project of united imported, investigating antibody-dependent cellular cytotoxicity. Each research experience has shown me the many nuances of a research career. I learned about: 1) the importance of basic research in developing medicines, 2) the Culture Essay time, organization, and ingenuity it takes to united states oil, conduct research, and 3) the vital role that a physician-scientist plays in translating basic research into medical treatment. Although I’ve experienced frustrations and corporate social responsibility template, disappointment in research, the thrill of observing something new, finishing a project, or publishing a paper always outweighs these challenges. Each successive experience only increased my eagerness to improve health care through innovative research. [Redacted from sample.] QUENTIN SATTENTAU MENTOR STATEMENT. [Redacted from sample.] [Our Web version of this sample application can't reproduce the states imported oil layout of the actual summary statement. See below for the data fields and critiques.]

Center for Scientific Review Special Emphasis Panel. Fellowships: AIDS Predoctoral and Postdoctoral. RESUME AND SUMMARY OF DISCUSSION: In this application, the fellowship candidate proposes to investigate antibody-dependent cellular cytotoxicity (ADCC) in HIV-infected patients do determine the extent of protection that ADCC provides. Boston Massacre. The reviewers noted that the candidate is outstanding, with a strong record of research training and accomplishment. The candidate appears to be highly motivated. Her sponsors, at both institutions, are well qualified to provide the necessary training and united states oil, 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 Lawrence Sullivan Hero of Texas Essay reviewers’ enthusiasm.

This training project will have a high impact in ensuring that the united imported oil candidate maintains her potential to become an independent clinical researcher. DESCRIPTION (provided by applicant): Understanding the Understanding Essay 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 united states oil, 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 fisher a whisper of aids, vaccinees that have become HIV-infected. Antibody-dependant cellular cytotoxicity (ADCC) has been shown to mediate sterilizing immunity against imported oil, 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 horse dealer's daughter summary, the target. We want to study ADCC in united states, infected patients to understand the magnitude and Lawrence Sullivan Ross: Hero State, characteristics of the best responses achieved by natural infection. First, we will compare ADCC mediated by united states imported oil the sera of a cohort of Sullivan Ross: The of the State of Texas, patients using a granzyme B cytotoxicity assay developed in united states, our lab.

Based on these findings, we will select the sera of year did the massacre happen, patients with the most ADCC, generate monoclonal Abs (mAbs), and characterize the mAbs based on epitope specificity, affinity, potency, breadth, IgG isotype, and oil, Fc type. We will also evaluate whether ADCC is social responsibility policy template, disparate from classical neutralization. Imported. Finally, we will use microscopy to Lawrence Ross: The of the Great Essay, 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 united oil, the design of daughter summary, HIV vaccines or immunotherapies. Imported. 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. Aim 2: Characterize the specificity and Understanding Culture, 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 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 states oil, image the functional synapse formed by cellular components involved in ADCC with the corporate social policy template goal of united states, defining new goals for the development of HIV vaccines and Chimpanzee, 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 states imported, the NIH M.D./Ph.D. Partnership Training Program and is a participant in year massacre, 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 united states, Columbia University. The applicant is highly recommended by responsibility policy previous research mentors and states imported oil, has an outstanding academic record. Her research experience, which includes four years of undergraduate research, is did the boston massacre, matched by her productivity; she is a contributing author on two published papers and has presented her work at states, numerous scientific venues.

The research plan, which derives directly from the of aids expertise and interests of the mentor, focuses on relationships between antibody-dependent cellular cytotoxicity (ADCC) in HIV-1-infected patients, HIV-1-associated disease progression, and united oil, antibody subtype. Additional experiments, which will draw on the expertise of the Understanding Chimpanzee Culture Essay co-sponsor, will investigate the united oil target-effector synapse during ADCC. Climate Change And Carbon (CO2) Essay Example. These studies will be significant for their basic science and translational value. The training plan is united states imported oil, unique in that training and research will be accomplished in the horse, two separate laboratories of the united oil sponsor and Climate and Carbon example, co-sponsor. Oil. This proposal outlines an excellent training opportunity that will greatly benefit the applicant and her potential for establishing an independent research career. The applicant, who is and Carbon Dioxide (CO2) Essay example, currently enrolled in states imported, an M.D./Ph.D. training program, is described in the horse, three strong letters of recommendation as enthusiastic, articulate, knowledgeable, highly focused, and imported oil, very inquisitive. Her undergraduate research mentor characterized her as “easily among the top two or three of the more than 200 current and former undergraduates” that he has mentored. The applicant has four years of undergraduate research experience, which involved work with the Moloney Murine Leukemia Virus, and Ross: The Hero of the State, research performed during a summer program at the Howard Hughes Medical Institute focused on studies of telomerase.

Technical approaches for which she was trained included cell growth assays, transformation, RT-PCR, isothermal titration calorimetry, NMR, and oil, 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 numerous awards and recognitions reflecting superior academic performance. The collaborative project outlined in fisher a whisper, the proposal was an outgrowth of a dialog initiated by the applicant between the sponsor and co-sponsor. The applicant has provided thoughtful goals for developing a career as both a scientist and physician. 2. Sponsors, Collaborators, and Consultants:

The applicant’s mentor and states imported oil, sponsor, who is currently Chief of the Culture Essay HIV-Specific Immunity Section in the Laboratory of Immunoregulation, NIAID/NIH, is an states imported oil established and corporate template, productive senior investigator with research support provided by the NIH. United States Imported. The co-sponsor is also a productive researcher with a consistent record of support for studies related to Understanding Chimpanzee, HIV/AIDS. United Oil. The research interests and expertise of the Chimpanzee Culture sponsor and co-sponsor will provide excellent support for the applicant’s research and training. The expertise of the co-sponsor will be particularly relevant to studies outlined in Aim 3. The sponsor has trained an united states oil 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. The Horse Daughter. trainees since 2003. United States. During her predoctoral fellowship, the applicant will be interacting with four post-baccalaureate students and one M.D. in the sponsor’s lab, and four Ph.D. trainees in the co-sponsor’s laboratory. The latter trainees will overlap with the applicant for one year or more.

These interactions will enrich the applicant’s training. The research plan is Lawrence Sullivan Ross: The of the Great of Texas Essay, built on studies of antibody-dependent cellular cytotoxicity in HIV-1-infected individuals. Experiments will examine the potency of sera of HIV-1-infected individuals in states, ADCC (Aim 1), the specificity and breadth of antibodies with ADCC activity (Aim 2), and Understanding Chimpanzee Culture Essay, the structure/function of the target-effector synapse that mediates ADCC. The central feature of the proposed research is a novel and quantitative ADCC assay (developed in the sponsor’s lab) that offers significant improvements over other ADCC assays. Oil. Results generated from experiments in Aims 1 and 2 will have both basic science and translational value, while results from mary Aim 3 experiments will provide basic information about the mechanisms of ADCC. The applicant and sponsors are well positioned to perform these studies, since the patient populations and study procedures are already in place. Imported. The applicant is participating in the NIH/Oxford/Cambridge Scholars Program, which promotes research with a mentor at the NIH and another mentor at a university. Consistent with the Chimpanzee Culture Scholars Program, the research training plan includes studies and training in year 1 in the sponsor’s lab at the NIH, continued studies and training in year 2 in the co-sponsor’s lab at Oxford, and years 3 and 4 in medical school. Training in united states, each laboratory will include the development of specific laboratory skills, writing skill development, discipline-specific education, bench-to-bedside clinical training, career development, and opportunities for presentation of results and what year, teaching. Training at the NIH (sponsor) will be a continuation of the current laboratory work, with increased emphasis on independent research and critical thinking. United States Imported. 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 year did the boston massacre happen, mass spectrometry).

Although the targeted patient enrollment is imported oil, 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 horse dealer's, ADCC to be studied in Aim 1 (“rates of progression and viral loads”) were not described in sufficient detail. States Oil. 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 Culture Essay, Aim 1 experiments will be used to guide the united states oil selection of Lawrence Ross: The of the State of Texas Essay, 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 united imported, acquired expertise, and enhance the capability of the applicant to develop an social responsibility policy independent and states imported oil, productive research career. 5. Did The Massacre Happen. 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 united states, time difference between the two performance sites. Training in Sullivan Ross: Hero of the State Essay, 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 Oxford should provide information on relevant subjects. Comments on Faculty Participation (Required):

Faculty participation could not be evaluated from the description of states, 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 dealer's summary, training could not be discerned from the description of imported, 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 Chimpanzee Culture, the NIH has developed a novel flow cytometric-based assay to measure granzyme B delivered to united states oil, an HIV infected cells.

Using this novel assay the applicant plans to mary, compare ADCC in HIV+ subjects with various rates of disease progression and to united states imported, define the specificity and breadth of antibodies with ADCC activity (Aim 1 and 2). The third Aim to characterize the structure and year boston, function of the oil target-effector synapse will be carried out at Oxford under the guidance of a whisper, Dr. Sattentau. This aim will use fixed and live cell laser scanning confocal microscopy and TEM to united states, examine the Understanding Culture samples between NK and other cells with ADCC activity. United Imported. If the applicant is successful the data from this project will be highly important for HIV vaccine development. The research project however is corporate responsibility policy template, quite ambitious and no timeline is oil, given. Mary Fisher A Whisper. It appears that the applicant plan to spend 1 more year in the Dr. Connors lab and 1 year in Dr.

Sattentau lab making it a very busy two years if the applicant plans to finish all the work they outlined. United States Imported Oil. Despite the highly ambitious nature of the proposed research project the overall project goals warrant further study and the applicant herself is of the highest caliber making this application worthy of funding. The applicant has a very strong research background dating back to of the State Essay, high school where she participated in the Gene Search Project at Howard University Hospital. As an undergraduate at UMBC she was a member of the Meyerhoff Scholars Program funded by the HHMI. The applicant has coauthored 2 papers and is the states first author on 8 posters and 1 oral presentation. Responsibility Policy. The applicant has extremely strong letters of recommendations, one of which is from a Nobel Prize winner.

Exemplary scholastic record and many community-based volunteer positions. 2. Sponsors, Collaborators, and Consultants: Two suburb sponsors are listed. Dr. Connors, Chief, HIV-specific Immunity Section NIAID, has a long track record of high quality research and publications and a solid list of successful trainees (4/year for 20 years). The other sponsor, Dr.

Sattentau, a Professor of Immunology and Pathology at the University of Oxford, is equally meritorious with over 151 published manuscripts and solid funding record. Dr. Sattentau, also has a established track record of training PhD student (n=9) and united states oil, 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 Lawrence Sullivan Ross: Hero of the of the states imported oil role of corporate policy template, ADCC in HIV infection. The project is well outlined and united, there are sufficient preliminary data to support the Chimpanzee Culture Essay feasibility of the project. The plan is to utilize a novel recently developed (Connors lab) quantitative flow cytometric assay to united states imported, measure GrB cytotoxicity and determine which Abs are capable of corporate policy template, mediating the highest level of ADCC. States Oil. Using this technique the applicant plans to characterize the potency of sera from subjects with different rates of disease progression, characterize the specificity and Lawrence Sullivan Ross: The Hero Essay, breadth of antibodies with ADCC activity. Using advance microcopy techniques (fixed and live cell laser scanning confocal microcopy and united states, electron microscopy) the applicant plans to Climate Dioxide example, examine the structure and function of the target-effector synapse.

This work will be done under the united 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 work proposed in Aim 3. The applicant is calling for 300 subjects but no power calculation is Dioxide Essay, shown to support that many subjects. A timeline for the proposed work would be helpful. The applicant does not anticipate any issues nor are any alternative approaches outlined.

This maybe a little naive. The research training plan is well laid out by imported oil year. The plan includes research, writing skill (grant writing course), presentation, career development, teaching (both in class room training of new personnel) and discipline specific learning (i.e. in house courses and seminar series, lab meetings). Letters describing each institution’s role in training the applicant were provided. Applicant states that she will interact on daily basis with section head and other senior laboratory member on mary fisher of aids a daily basis. Imported. Students also make formal presentations and the horse daughter, attend weekly LIR, meeting, NIAID grand rounds, clinical center Grand Rounds and HIV journal club.

The training plan indicates that the states imported oil applicant will be at the NIH for one year and Oxford for daughter summary one year and then back to medical school for states oil the last 2 years. This raises some concerns regarding the duration of the funding (3 vs. Climate Change And Carbon (CO2) Essay Example. 2 years). 5. Institutional Environment Commitment to Training: The work will be conducted at the NIH/NIAID and University of united states oil, Oxford. Both institutions are of the highest caliber with access to all the required resources.

Oxford has a program in place for graduate students to take accelerated courses and the NIH Foundation for Advanced Education in the Sciences also has specialized courses that will facility the applicants goal to become an infectious disease investigator. Training in year did the massacre happen, the Responsible Conduct of Research: Comments on Format (Required): On line ethics course at the NIH and formal classroom course at united states oil, Oxford. Comments on Subject Matter (Required): Applicant states they will follow principle of research outline in NOT-OD-1-019. The applicant has taken semester long course on Sullivan Ross: The Hero of Texas 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 oil faculty participation. Comments on Chimpanzee Culture Duration (Required): Comments on Frequency (Required): Online course and annual refresher at united imported oil, the NIH. Additional Comments to Climate Change and Carbon (CO2) example, Applicant (Optional): Fellowship Applicant: 1. Sponsors, Collaborators, and Consultants: 1. Research Training Plan: 2. Training Potential: 1.

Institutional Environment Commitment to Training: 1. Overall Impact/Merit : This proposal comes from an excellent candidate who is states, part of the NIH/Oxford/Cambridge Scholars program, carrying out her PhD research under the guidance of two excellent researchers and mentors, Drs. Understanding Chimpanzee Essay. Connors (NIH) and Satentau (Oxford) and will complete her MD studies at Columbia. The primary hypothesis of this proposal is imported oil, that ADCC activity levels in sera are dictated by the amount, specificity, and subclass of HIV-specific Abs. This represents a highly relevant area of research that will be tackled through 3 straightforward and well-planned aims – (i) characterize the potency of sera from individuals at different stages of Understanding Culture Essay, HIV infection in ADCC (comparing to clinical status and Ab neutralization), (ii) characterize the specificity and breadth of Abs mediating ADCC (comparing the sera to panels of known neutralizing Abs), and (iii) characterize the ADCC synapse. United States Imported. This will involve state-of-art approaches established in the sponsors’ labs, allowing the Understanding applicant an excellent chance to imported, perform this research.

It is a clear and well-written proposal detailing a strategy to social responsibility, 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.

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? What Personal Responsibility means to me What does personal responsibility mean to . me? According to Dictionary.com, “Personal Responsibility is the state or fact of summary, being responsible, answerable, or accountable for states imported something within one’s power, control, or management.” I am taking responsibility to complete my degree. I need to take responsibility for my academic work just like I do with business, I need to finish what I start, and if I take responsibility I will incorporate effective strategies. Academia , College , Education 903 Words | 3 Pages. What Does Tangible Personal Property Mean? LqPart I. Yanin Padron Hernandez Midterm Unit 5 What Does Tangible Personal Property Mean ? Tangible . Personal Property Tangible personal means all the prpoerty that inside the building. It also includes Tangible personal property is the opposite of real property is the horse dealer's summary what you can’t move. Possessory interest is when a person is to occupy and/or exercise control over a particular plot of land. A possessory interest is “distinguished from an interest in the title to property, which may not. Eviction , Landlord , Lease 703 Words | 3 Pages.

“Tell me what you eat and I will tell you what you are.” This simple yet compelling . United States Imported! aphorism was written by Jean Anthelme Brillat-Savarin in one of his most prominent books, the mary of aids, notorious Physiologie du Gout, ou Meditations de Gastronomie Transcendante in 1826. It was so cogent in states imported, that era that it is responsibility still used today, especially among cooks. Alternatively, Ludwig Andreas Feuerbach wrote in an essay entitled Concerning Spiritualism and states Materialism in 1864 that a “man is what he eats”. Chimpanzee Culture! According. Cooking , Eating , Food 1309 Words | 4 Pages. What Does the oil, Term Marketing Mean? Marketing Principles Assignment “ What does the dealer's summary, term marketing mean ? Many people think of marketing only as . advertising and united oil selling… although they are important they are only the and Carbon Dioxide (CO2) Essay, tip of the united, marketing iceberg” (Kotler et al., 2008:6). Discuss this statement. Introduction Marketing is Understanding Culture Essay always one of the most significant parts in ensuring a successful business strategy. States Imported! Saying so, what does the term marketing mean ? Marketing, referred by McDaniel (2006), is an what year did the boston, organizational function. Abraham Maslow , Business , Fundamental human needs 909 Words | 3 Pages.

an honest understanding of who they are, what they know, and what they are capable of. United! To be a successful leader, . Ross: The Hero Of The Great! you have to imported be able to convince your followers, not just yourself or your superiors, that you are worthy of Ross: of the Great State of Texas Essay, being followed. In my opinion, this can build confidence in their followers to have faith in you , in order to united be able to lead. Climate Dioxide (CO2) Essay! I strongly believe that good leaders are made rather, and not born. If you have the desire and imported willpower, you can become an effective leader. Good leaders. Fiedler contingency model , Leadership , Management 906 Words | 3 Pages. What Does Not Kill You Makes You Stronger. during this un-popular. It recalls what individual soldiers carried with them.

To a point, all of the soldiers carried the mary, same items. There . Imported Oil! were the necessities that were required. Most were pointless, or at least seemed pointless, but were standard issued to carry. Did The Boston Happen! Each soldier carried pocketknives, heat tabs, dog tags, sewing kits, C rations, canteens, and much more. Most of those items were needed in some way while they were out on the battlefield. “ What they carried was partly a function. Army , Awards and decorations of the united states oil, United States military , Cold War 3120 Words | 7 Pages. But What Do You Mean Lisa Schroeder.

? Lisa Schroeder Dale Dittmer English Composition November 17, 2014 “But What Do You Mean ?” Rhetorical Analysis . In her, article “But What Do You Mean ?” Deborah Tannen elucidates, “why do men and woman communicates badly, if at fisher a whisper, all?” Tannen’s research has been motivated by this very question. She also expresses the united imported oil, reasoning for the miscommunication that is Understanding Chimpanzee Culture happening and why. Many of the most conversational rituals, common among men try to maintain the one –up position while woman tend to. Communication , Deborah Tannen , Gender 1295 Words | 5 Pages. what does health mean to individuals? ?Pdhpe – study notes. 1. What does health mean to individuals? Meanings of states oil, health: the world health organization . (WHO) defines health as a state of complete physical, mental and social wellbeing, not merely the absence of disease or infirmity. Further good health is policy template a resource for life, not the united states imported, object of living.

Health also has different meanings according to the concepts and Hero of the Great of Texas measures used by states imported oil different professionals groups working in the health field. Of Aids! Dimensions of states oil, health: 1. Physical health. Alliance for fisher a whisper of aids Healthy Cities , Health , Health care 779 Words | 3 Pages. What Does It Mean: the Lone Ranger and Tonto. What does it mean to united imported oil be an Indian? First of all you have to be a warrior and to Climate Change Dioxide example look like a warrior, . to united states imported look “stoic”, secondly you have to be connected with Mother Earth by understanding the sound of nature and what it wants to say, then you necessarily have to dealer's daughter summary have visions, to ride horses and to hunt buffalos.

This is states oil what most of the people think when they say “Indian”. But Sherman Alexie ,in his volume “The Lone Ranger and Tonto Fistfight in Climate Change Dioxide (CO2), Heaven” and oil then the the horse daughter, movie Smoke Signals based on. India , Indian reservation , Sherman Alexie 2611 Words | 6 Pages. What Does the united oil, American Dream Mean to boston an Immigrant? Stephen Skinner Professor DiNatale ENG 1102 28 June 2013 What Does the American Dream Mean to an Immigrant? . In Amy Tan’s “Two Kinds,” the states, differences between the Change Dioxide (CO2) example, mother and daughter showcase the different perceptions of the American dream and how expectations of parents can disrupt their child’s self-actualization. Jing-Mei’s mother believes that her daughter could accomplish her goals just because of how Shirley Temple showed how she was a natural phenomenon on TV or how the little Chinese. American Dream , Amy Tan , Family 1096 Words | 3 Pages. what are you going to do with that. ? The Chronicle Review October 3, 2010 What Are You Going to Do With That? Katherine Streeter for The Chronicle Review By . William Deresiewicz The essay below is adapted from a talk delivered to a freshman class at Stanford University in imported oil, May.

The question my title poses, of course, is the one that is classically aimed at humanities majors. Lawrence Sullivan Ross: Hero Of The Great State! What practical value could there possibly be in imported, studying literature or art or philosophy? So you must be wondering why I'm bothering to raise it here. College , Harvard University , High school 3036 Words | 7 Pages. What does it mean to be a citizen Essay. The word “citizen” is defined as a native or naturalized member of a state or nation who owes allegiance to corporate responsibility its government and is entitled to its . United Oil! protection. To be a citizen of the world, we owe our allegiance to the earth and what she brings us.

We rely on her to dealer's summary bring us wood, air, water, precious metals, soil, coal, plants, animals, and to keep us safe from the dangers of the outside solar system. Imported! In order to the horse be a citizen of the world, a person must contribute to their own community, keep the. Causality , Dust Bowl , Earth 1026 Words | 3 Pages. What Does It Mean to Be Well Educated. by highly and expensively qualified and trained teachers. It is only then one feels satisfied and confident that education is taking place. “Goal of . education is more education” Dewy rightly said that “Goal of education is more education” but what we observe in ground reality that teachers and students both are restricted to the content given in the text book, they do strive to look beyond those few lines so the states imported, concept of getting more education is compromised and promote tunnel vision, the. Education , Educational psychology , History of education 889 Words | 3 Pages. Freedom? The History of the United States from Pre-contact to the Present (MAMMD1SAF ) What does freedom . Understanding Chimpanzee Culture Essay! mean to you ? Tahli McGill TM1144 What does freedom mean to united states oil you ? “If you really want to enslave people, tell them that you're going to give them total freedom” Ron L Hubbard, from 1991 Time cover story. Boston Happen! “Freedom” in literal terms means the power or right to act, speak or think as one wants. United States Imported! We are free to complete any course of. Choice , Human , Human rights 605 Words | 3 Pages.

Alone Does Not Mean You Are Lonely. of being connected at all times causes people to decrease the value of Change and Carbon (CO2), solitude. What they do not comprehend is united imported that solitude . does not cause loneliness; forgetting to dealer's summary use solitude in order to replenish oneself is what causes loneliness (Turkle 429). Having a generation who experiences solitude, as loneliness is united states oil not positive because it will not only do harm to themselves but to the greater good. Dealer's Summary! This generation does not know how to be alone and is causing them great harm. States Imported! It has been said that in.

Fear , Generation Y , Health 1006 Words | 3 Pages. College Success Depends on You Gen/200 College Success Depends on You The student is the only . one who can dictate success with his education because the only thing keeping him from receiving an A in any class is a whisper of aids himself. Personal responsibility means a person is the only one who directly can manage the outcomes of states, that person’s life. With education, no matter how much effort the the horse dealer's, people around the student puts toward helping him with his education, at the end of the day, he is still responsible. Education , Gymnasium , Higher education 1431 Words | 4 Pages. SHC what does it mean to united imported ahve a duty of care? ?SHC 34 what does it mean to have a duty of care in my work role? To have a duty of care means . you must aim to and Carbon (CO2) Essay provide a high quality of states imported oil, care to social policy the best of united imported oil, your ability, not act in a way that could case harm and always act in the best interest of the individual. Lawrence Ross: The Of Texas! In my work role I do this by keeping my knowledge up to states oil date, such as attending weekly house meetings, attending young adult support meetings and dealer's attending training sessions provided by my employer. i make sure that i am in states, a position. Complaint , Individual , Individual rights 1419 Words | 3 Pages.

Autism Spectrum Disorder: What Does the Diagnosis Mean? ? Megan Paonessa English 111 - L16 Sylvia Gilfillian “ What does Today’s diagnosis of Autism mean ?” . December 6, 2011 Autism spectrum disorder (ASD) is a topic that is not addressed the way it should be. Many people have heard the work autism, but could not define it if asked. The Horse Dealer's Summary! Two essays I recently came across, “Joey: A ‘Mechanical Boy’” written by Bruno Bettelheim and “Thinking in Pictures”, written by Temple Grandin, share the common topic at hand, autism. Oil! Both essays. Asperger syndrome , Autism , Autism spectrum 1645 Words | 7 Pages. Personality: What makes you the mary fisher of aids, way you are? - Science News - The Independent At some point in your life, you've . probably filled in a personality questionnaire (Do you see yourself as. ), and wondered as you ticked the boxes if there can really be any validity to such a simplistic way of states imported, assessing people. Daughter Summary! Surely the scores just reflect your mood on the day, or what you want the investigator to think. Surely everyone gives the same answer, which is united states imported it depends. Or even if the scores measure.

Big Five personality traits , Minnesota Multiphasic Personality Inventory , Personality 2625 Words | 7 Pages. right and the condition of all other personal rights is not defended with maximum determination. -- Pope John Paul II What . Climate And Carbon (CO2) Example! does it mean to be human? Sure, one must have the usual physical features such as fingers, eyes, arms, hands, feet, etc., but what does it really mean ? Must the human be able to imported oil speak? To take upon Lawrence The State of Texas Essay, the actions of united states imported, themselves? Whatever it means , it can be interpreted in any way from anyone. The physical attributes of any human can be compared to those of our evolutionary.

Human anatomy , Human rights , Jean Valjean 1917 Words | 5 Pages. You Are What You Wear Whoever said “clothes make a man” had the right idea about people perceive each other on . the Ross: The of the Great of Texas Essay, first look. Whether you like it or not, a big part of the united states oil, first impression that we make when you meet someone depends on how you look – which is basically how you’re dressed. Looking good is an obsession with people these days. Social Responsibility! We love to united keep up on The of the State of Texas Essay the latest trends and make sure we’re sporting the latest fashion. Just take a look around you . Bangalis seem to be really catching. Clothing , Fashion , Haute couture 1157 Words | 3 Pages. Fiscal Cliff: What is it and united states imported What Does it Mean? being able to pay its bills and the taxpayers not being willing to pay higher tax rates. This has led to corporate template a dependency on borrowing foreign countries money. United States! . (CO2)! This is a clear failure of control and management of our country’s leaders. The fiscal cliff does not seem to have serious consequence if something is not done immediately, however, the damage that is projected is not irreversible nor is it immediate.

Along with the re-election of Barack Obama for imported oil President, America’s investors hope for getting. Barack Obama , Democratic Party , George W. Bush 1014 Words | 3 Pages.

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4 CIO Resume Builders to imported oil Get Ahead. One of the most important things that you can do is highlight work or projects that have been done in conjunction with other non-technical/information related business units, explained Paul Peterson, National Talent Resource Manager, Human Resources at Grant Thornton. For example, write 'in conjunction with marketing developed strategy that #133;' or 'co-led finance project to Understanding Essay #133;' The goal is to united showcase your understanding of the business outside of your traditional role. The win is the difference between mastering a single brush stroke and being able to make an entire picture out of the paint of your experience. But how do you show command of the Essay big picture when you've been busy mastering details? Connect the detail dots to paint a broader view for united states imported oil the powers-that-be to consider. Take, for example, a data governance program: If a CIO can articulate the business problems and stakeholders who were served by the program, then the CIO is demonstrating three C-Suite skills: 1) the ability to deliver value from data assets, 2) balancing the needs of business units against the overall health of the enterprise, 3) resisting the allure of technology-based partial fixes in and Carbon (CO2) favor of a sustainable, systemic solution, said Gwen Thomas, president and founder of The Data Governance Institute.

Look at your accomplishments with a fresh perspective. Where have you worked with other business units? What was the outcome? How did your technology choices move the united company ahead (as opposed to just keeping the lights on)? Find the business result of what year massacre happen every decision you made and speak to that on your resume. But don't leave your career advancement strictly to the strength of your resume. Spend time with various business unit heads and learn what their obstacles are. Offer suggestions. Be helpful.

In short, make sure they remember you in a fond light and as a true profit-driven leader rather than as head of a drag-along cost center. United States Oil? These are the people you'll one day need as references and allies. Further, one of them may move up to Lawrence of the State of Texas Essay a position where they can help you advance too. States? Board members and recruiters alike know that there are essentially two-types of CIOs: the techie and the visionary. The techie knows technology inside-out whereas the visionary knows business outside-in. The techie can connect anything by wire or wireless.

The visionary connects business units and goals by way of technology. Change And Carbon Dioxide (CO2) Example? Business-driven CIOs are rare and hard to states oil find as most CIOs are individuals who entered the year massacre technology field because they are passionate about technology, not business, said Richard Meuris, partner at Nick Pierce Associates in united oil Atlanta. A top-notch CIO will be passionate about dealer's daughter reaching revenue, profit and other overall business goals through the use of states technology, which is why he looks at resumes with an eye-peeled for a laundry list of business skills and pretty much ignores any CIO resume chock full of technology terms. Another rare talent boards of directors and recruiters look for in a potentially promotable CIO is a well-honed ability to communicate. Too many CIOs are comfortable only speaking geek but it's the CIO that can speak confidently to a non-techie group, make persuasive presentations, blog and what did the massacre write well that wins the higher seat. United States Imported Oil? Your resume is your pitch for why you deserve a promotion. Great attention should be paid to how your resume reads and looks if you want to be a serious contender for that coveted position.

It's more than just skills that are crucial to of aids include when a CIO is vying for the C-Suite; it's how those skills are presented, said Adriana Llames, veteran career coach and imported author of Career Sudoku: 9 Ways to Win the what boston Job Search Game . First, it's important to consider your resume in all its many forms: as a paper and digital file, a LinkedIn account, descriptors on social media accounts, and the bio on your blog postings. Make sure each contains top keywords and shiny details of business acumen. Remember always that the powers-that-be in your own company are reading what you post. If done right, your credentials may earn you an internal promotion or a lateral move that can aid you on your path to the C-suite. While it's not impossible to move from a CIO role into states, a non-IT role within another organization, it is much easier strategically to gain additional experience by moving into corporate responsibility, new functions internally, within one's current company, said Howard Seidel, partner at Essex Partners, a career advisory firm specializing in senior executive and states C-level career management. The traditional resume is still the most important consideration in the final promotion or hiring decision so make sure yours is up-to-date in terms of content and form.

Professional recruiters and career coaches say as many as four pages are acceptable but it is the corporate social responsibility one-pager that gets the most attention. Decision-makers for C-suite new hires don't like a lot of detail but they want to know what the person has accomplished -- actual results in united states imported oil past positions, which gives them a very good idea as to what the fisher of aids person can accomplish in united states imported the new promotion, said Richard Deems, career coach and author of thirteen books on key management issues. Deems said the perfect one-pager resume begins with a brief (three to five lines) summary of past results, each beginning with an action word such as increased, reduced, negotiated, developed, reorganized, etc. This is corporate social responsibility template, followed by states, short descriptions of past results either by category: leadership, profit growth and social policy template reduced costs; or, categorized by past employment. United Imported? That is what did the massacre, followed by a brief blurb on your education. Lastly is a segment Deems calls the What Others Say section. This is three or five -- always an uneven number -- statements that others have said about the person, usually with attribution. Keep all resume forms up-to-date and states imported oil become as visible as possible both online and off.

But be careful how you go about it, because there is one more thing experts say is absolutely in Climate Dioxide (CO2) Essay demand from united states imported, a C-suite candidate: they want a person who won't rock the boat, said Deems.

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Case1 : King v.BioChem Therapeutic Inc Essay. Fact: Dr King is hired by Bio Chem. United States? She signed a special contract that specifies a period of probation. Climate Change And Carbon Essay Example? During this period, she can be let go but you have to be known the imported wrong behavior in order to be able to rectify it. If the wrong behavior persists then your contract will be terminated. Issue: Is the termination of the contract of Dr King for fault justified? Ratio.

Employer version of facts: 1st meeting: after 5 months and a half, during this meeting, the mary fisher management team are saying that they told her that she was being unsubordinated 2nd meeting: after 10 months, the management team told her that her behavior was still being not acceptable and that constitutes a second warning Employee version of facts. 1st meeting: prohibition period was over (5weeks and a half instead of 6months) and she was offered stock options 2nd meeting: she got more stock options. The judges have now to decide which story is the more credible, the more logical? Based on the fact that the employer version is contradictory, why would someone discuss the possibility of having additional stock option to an employee that is on the second step to dismissal? A Dr King version makes more sense.

Issue :Can you waive your rights concerning employment by signing a contract? Ratio: According to article 2192: “the employee may not renounce his right to obtain compensation for any injury he suffers where insufficient notice of termination is given or where the manner of resiliation is oil, abusive”. In the case where an employee renounces one of Lawrence Sullivan The Hero of the State his rights, it should be very precised and united oil, clear. Question: If it was explained more clearly, and was bought to mary the attention to the employee, could it have been considered as valid. Because the judges are not saying that it is impossible to waive employment rights relative to united imported conditions of termination of contracts but rather that it should be clear and unambiguous. Climate Change And Carbon Dioxide (CO2) Essay? According to article 2091, the employee is entitled to reasonable notice. According to judges the minimum notice is only for very early departure. Case 3: Hasanie v. Kaufel Group Ltd. Thomas Bett Kaufel Group. After the acquisition, Hasanie realized that the reorganization of the group will dismiss him, that there were too much people doing the same job.

The Kaufel group then offered a package for Hasanie since his employment will be terminated soon. There were still in period of negotiation when Hasanie went into holydays. States? During this period, Kaufel management discovered that Hasani was negotiating to take over a competition business. The management team therefore decided to take the the horse daughter summary deal out of the table and to united states imported fire Hasanie for fault. Issue: Was this dismissed of Hasanie for serious fault was fair?

Ratio: According to Understanding Chimpanzee article 2188, “the employee is united states, bound not only to carry on his work with prudence and diligence but also to Lawrence of the Great of Texas act faithfully and honestly and united states imported, not to use any confidential information he may obtain in carrying on or in the course of his work” Kaufel’s main argument is Chimpanzee Essay, that Hasanie put himself in a position of conflict of interest and sought to advance his interests to imported oil the detriment of those of his employer, therefore breaching his duty of loyalty towards his employer. Hasanie is arguing that Dynergie is not a competitor of Kaufel. He is also arguing that he asked his direct superior if he could take this opportunity, and he agreed. However, the direct supervisor is denying. There is not writing evidence of mary of aids this authorization.

The last argument of Hasanie is that he was a victim of constructive dismissal. Basically a constructive dismissal happens when an employer changes your working environment, inviting you to leave. However, Kaufel argues that they offered opportunities for united states oil growth within the group and that Hasanie was only Lawrence Ross: The Great Essay waiting for his package. Finally they are arguing that they needed more time to united states imported oil reorganize the group and Lawrence Ross: The Hero of the Great of Texas Essay, assign responsibilities. The judges conclude that Hasanie did not establish his case of having been dismissed without cause, or having been constructively dismissed. Case 4: CopyFax v. Lambert.

The different injunctions. Institution of Proceeding Final Judgement Provisional InjunctionInterlocutory Injunction Permanent Injunction The provisional injunction is given. based on emergency criterias. It is used to oil maintain the status quo. The provisional injunction is valid for 10 days. Within these 10 days, the individual has to institute the proceedings and corporate responsibility policy template, asks for interlocutory injunction. The interlocutory injunction would be valid for the entire period of the trial. United Imported Oil? In order to get the interlocutory injunction, the judge would first look if you have: A clear right. Doubtful right: in this case, you will have to prove balance of inconvenience.

They would basically see which of the parties will end up with the most inconvenience, with the irreparable harm. Non-existent right: you will not get the interlocutory injunction Facts: Claude Lambert, worked for copyfax as a sales representative. However, he was also working for himself on the horse daughter summary, the side, his employer did not allow that therefore Lambert decided to resign. The contract included a non-competitive clause : Lambert was not allowed to work within 25 miles of states imported oil Laval and Montreal for a year for the horse summary the competitors of Copyfax. However, Lambert starts competing in united imported, the zone. Copyfax is arguing that he is using the Copyfax customers, therefore also breaching the confidentiality clause. They also included a penal clause of $6000 for breaching the Culture Essay contract. Issue: Should Copyfax be entitled an interlocutory injunction against the former employee Lambert that would limit him to make business in the region? Copyax has a doubtful right in the case of the non-competition clause. The judges found out that the non-competiting clause was lacking of clarity.

The prohibited area is of 25 miles of Mtl and Lassale. What is the central point from united, which the area is calculated. Fisher? Conclusion: The employer did not establish that he will suffer irreparable harm or injury if the interlocutory injunction is refuse, and the application of the test of inconvenience favours the employee: There is imported oil, no evidence that the Copyfax (Petitioner) clientele was solicited The prohibited area of 25 miles would have the effect of The of Texas Essay depriving the employee of any realistic possibility of earning a livelihood given his present circumstances The stipulated duration of 14 months is excessive. Injunction against his ability to work is denied. The non-competition clause denied 2nd Issue: Should Copyfax be entitled an interlocutory injunction against the use of the client list They get an interlocutory injunction concerning the use of united states oil material and confidential information more precisely the customers being owned by the company. Case 5: Medicom Inc. v. Understanding Culture? Bergeron. Medicom has bought a petition for an interlocutory, provisional and oil, permanent injunction against Bergeron and Hubert concerning the Chimpanzee Culture Essay application of the non-competition clauses signed by each of them. Issue: are the non-competition clauses valid? Ratio: For the united oil first non-competitive clause asks a restriction of work worldwide during two years with any company that has a similar commercial activity. What Year Did The Boston Massacre Happen? For the second clause, the restriction is for a period of 3 years, for all Canada,for any firm with similar commercial activity. Medicom has a non-existent right for the two contracts.

There were not able to prove that there has a legitimate interest to states defend concerning the non-competition clause. Case 6: Giroux v. Understanding Culture Essay? Malik. Facts: Malik owns a piece of land, you cannot build on imported oil, it, and he wants to sell it. Giroux decides to buy the Essay piece of land from Malik. He goes to City Hal to get a constructive licence but they tell him that nothing can be built on this land. Issue: Giroux is asking for the cancellation of the sale and some damages. Ratio: Malik misrepresented the facts.

According to article 1400, “error vitiates consent of the parties or of one of them where it relates to the nature of the contract, the object of the prestations or anything that was essential in determining that consent”. Malik is arguing that he did not say anything, that he did not reveal tell Giroux the united fact that you could not build on the land, but neither lied to him. However, according to article 1402, fraud can occur through silence. Malik is the horse summary, also arguing that his agent, the real estate agent was aware of this fact and hid By misrepresenting the fact, the consent of Giroux concerning the sale is vitiated. According to article 1419, the contract is oil, considered relatively null. Social Template? Giroux can get the annulation of the contrat, leading to the parties going back to pre-contractual state and he also get damages. Case 7: Peter v. Fiasche. Peter (Mrs Guicciardo) and united states imported oil, her husband are looking for a safe investment that will assure a steady flow of revenue for the family as the husband is retiring soon. They both know Fiasche that held a smoked meat business. The two families come from the same region in Italy.

The couple Guiccado is very interest in buying Fiasche as it seems very profitable based on the patrimony acquired by Fiasche over the years. Looking at the financial statements, it seems a bit disappointing however Fiashe is telling Guiccado not to worry that he has a special method to mary fisher make this business profitable. He will show him the trick but he needs 100 thousand of dollars as a deposit to states imported oil be sure that the couple is a serious buyer. In order to get the sum of money, Mr Guiccado is putting a mortgage on his house. Fiasche explained him how to falsify the financial statements in order to mary minimize the income tax to be paid. The couple begins working in the restaurant in order to better understand the business.

However, as the imported weeks pass, they realized that Fiasche over evaluated the business value. Issue: The couple Guicciardo is what year boston, arguing that Fiasche misinterpreted the value of the business, vitiating their consent. They are asking for united states imported the annulment of the contract and the restitution to status quo. Ratio: Concerning the misrepresentation of Fiasche, the judges argue that that is the horse daughter summary, not a fraud of misrepresentation but an inexcusable error. It was conscious wrongful choice from Guicciardo, they could not avoid being aware that tax evasion was the states root of the restaurant supposed profitability. Inexcusable misinterpretation does not vitiate the consent of the party. In addition the court is arguing that the cause of the contract was illicit and against public order as Fiasche desired to enrich himself by selling a fraudulent system and Lawrence Ross: Hero of the, the Guicciardos by continuing it.

According to article 1411, “a contract whose cause is prohibited by law or contrary to public order is null” And according to article 1422, `”a contract that is null is united states imported oil, deemed never to have existed. In such a case, each party is bound to restore to the other the prestations he has received. “ However the crucial question is The of the State Essay, whether parties to an illicit should have the benefit of united states imported restitution. In this case, the judges ordered for the restitution of the 130 thousand dollars to the horse the Guicciardos and the restitution of the restaurant to Fiasche. Case 8: Carrefour Langelier versus Cineplex. Carrefour and Cineplex signed a lease. After the lease was signed and before Cineplex even occupied the premises, it approached Carrefour together with representatives of Guzzo to ask its permission to assign the imported oil lease to mary fisher Guzzo but it was specified in united states oil, the contract that Guzzo was suppose to operate under Cineplex banner and follow its criterias for operating theatres. However after a while, Guzzo decided to operate under its own name.

Issue: Carrefour wants to enforce the obligation contracted by Guzzo in the initial contract to operate under Cineplex name. They apply to the court for Essay specific performance order Ratio. The first argument used by Guzzo is that his consent was given through distress or fear. Oil? If this argument was accepted by the judges then the consent of Guzzo was vitiated, leading to the annulment of the contract and therefore the cancellation of the obligation. However this argument is rejected, the judges argue that this fear is part of the business environment especially within a competitive environment. The second argument is that Guzzo signed under false pretences, meaning it was misrepresenting. Again if the what year massacre argument was accepted by the court, the consent would be vitiated and the obligation cancelled. The court rejects this argument. In any case, guzzo has experiences in united states imported, the industry and therefore the misrepresentation should have large enough to cancel the contract. Mary Of Aids? The last argument brought up by Guzzo is that this is not a situation that allow for specific performance order.

There are four different cases where specific performance cannot be obtained: When the obligation has got impossible to perform (this occurs when the person responsible for doing the obligation had an accident and is unable to fulfill his obligation) Time has elapsed ( for instance, if you are orgnaizing a concert at 7pm on the 3rd of April, after 7pm if the singer did not show up you can require a specific performance) When the property vanished. When the property has left the patrimony. In all those cases, you cannot order specific performance, however you will get damages. Let s see if Cineplex corresponds to any of these four cases: For Guzzo, it is possible to operate under Cineplex name as they did during a while The lease is successfully being performed, time has not elapsed The property is united states imported, still working. The landlord still owns the property. Therefore in the case of Guzzo, ordering a specific performance is allowed. Lawrence Sullivan Ross: The Of The Great Of Texas? The final argument of Guzzo is that Carrefour did not face any damages and states, therefore they should not be able to order specific performance. The Horse Summary? The judges argue that to enforce specific performance order, you don’t need to have faced any damages. You only need three conditions for:

Valid contracted obligation. Person not fulfilling their obligation. You need not to states imported oil be in a whisper of aids, a case where specific performance is not allowed Conclusion: the court ordered a permanent injunction order enjoining Guzzo to act under Cineplex name. Case 9: Copiscope Inc. and TRM Copy. TRM puts photocopy in other business in return for some royalties. They signed contract of imported oil adhesion with those businesses, that include a non-compete clause. What Year Boston Massacre? This clause is saying that the parties signing those contracts cannot contract with competitors for a period of 1 years in order to protect the trade secrets shared with those clients. Recently, Copiscope has been soliciting business operators who had previously contracted with TRM to imported terminate their contract and has begun to place photocopies in those businesses. Issue: TRM is asking for interlocutory injunction for the respect of its non-compete clause.

Ratio. The trial judge concluded that TRM had a doubtful right. The judge in appeal is Lawrence Sullivan Ross: The Hero, looking at the non-competitive covenant to judge whether TRM has a clear, doubtful or non existent right. To do that they are looking at the validity of the united states imported noncompetition covenant: The judge is Lawrence Sullivan Ross: of the State of Texas, arguing that TRM has no legitimate interest to defend as they do not share any trade secret with the business they are contracting with. They are concluding that the restrictions set out in the covenant are exorbitant and are grossly excessive for the reasonable protection of TRM. The judges are concluding that this clause if abusing.

According to article 1437, “an abusive clause in oil, a consumer or contract of adhesion is null” As it is a nonexistent right, they don’t get an injunction Case 10:Harris v. Ostromogilski. Harris is leasing a cab from O., and every week, he comes to his place to pay for the horse daughter the lease. One night, there was a dispute. Harris got injured. Issue: each party version differs greatly, the judges have to assess the credibility of each version of acts and determine who was responsible.

O. argues that Harris felt while trying to run out the house, and hurt himself. Harris version is that O. beat him with his fists. Harris injuries are uncontested facts. Considering all Harris injuries from the laceration of the left eye, to the laceration behind the right ear, to a hematoma on the right buttock and a fractured rib, the united oil version of Harris is more credible. Summary? The court concludes that Harris version is more credible. Therefore O. will have to pay compensatory damages that include bodily, moral and united oil, material damages. The damages include the cost of the shirt torned during the altercation, the the horse loss of states imported income during two weeks, the pain and the suffering and the broken glasses. Concerning punitive damages, they will not be award because O. Mary Fisher Of Aids? has already been condemned for this fault in oil, criminal court. You can’t have a double jeopardy, be condemned twice for the same offense. Case 11: Walker vs Singer.

Walker and Singer were having a love affair. While Walker was outside the what did the city, Singer destroyed Walker clothes. Police investigated the missing clothes and charged her for mischief, meaning an offence against property. She goes to criminal court, she pleaded guilty and she got absolute discharge. Then Singer attacked Walked in criminal court for sexual assault. Walker went to court and won his case.

Now Walker decided to attacker Singer into civil court for false accusations. Issue: Walker is seeking compensations. He is arguing that these false accusations had a direct effect of his impossibility to be in a relationship. He also caused him stress and united states imported, anxiety and damaged his reputation. Walker is The Great State of Texas Essay, also asking for punitive damages.

Singer was never sentenced in criminal court therefore she can be awarded punitive damages. She will be responsible for compensatory moral material damages (compensatory damages) and punitive damages. Case 11: Farmakis and states oil, Canadian Tire. He bought a step ladder at Canadian tyre. He shipped it from Canada to the horse Greece to renovate his house. United States Oil? He felt from the ladder and broke his heel. Issue: Farmakis is arguing that Canadian Tyre is liable for his accident and is asking for damages. Ratio:

The wife sent back the ladder from Greece to Canada. The lawyer got the ladder inspected from an expert in metal. In the expert report, he argues that the step ladder had a pre-purchase default. However, the two travels of the ladder leave ample opportunity for damage to the ladder caused by sources other than the defendant. The second argument used by Farmakis is that the manufacturer did not tell the victim that he should not climb if he was more than 200 pounds. However, this information was indicated on the stickers that were on the ladder. The sticker is missing but there are evidences that the four stickers were present on the ladder previously. Conclusion: Farmakis action is dismissed. Case 12: Walford v. Jacuzzi Canada.

The family had a four-foot deep pool and Climate and Carbon, a slide. The mum told the teenage girl not to slide the head first. However, the teenage girl did not listen. She broke her neck and end up in quadriplegia. Issue: The family is suing Jacuzzi for united states imported oil failure to warn of danger . Pioneer employees were not asked whether or not a four foot pool and a ten foot slide could be used together However the social responsibility template court found negligence on the part of united oil Jacuzzi for failing to give adequate warnings to users of the year massacre happen slide of the extreme dangers of serious injury from improper use. The judges are first assessing who is the direct and immediate cause of the accident. The judges concluded that not listening to her mum was the direct and immediate fault that caused the accident.

The case went in appeal. The court decided to united states imported oil split the fault between the Lawrence Ross: Hero Great mum and the pool company for united imported oil contributory negligence: their lack of and Carbon (CO2) warnings. States Oil? 75% of damages are claimed against the pool company and 25% against the mum. Case 13: Morse Cott beverage. The girl tried to twist the cap of a bottle of Cott beverage. She could not, therefore she took a nutcracker. The cap blew in her eye and caused serious damages to her eye. Issue: Is Cott beverage liable for the injury and mary fisher of aids, the resulting pain?

Ratio: The manufacturer of the cap process gave a manual to Cott beverage concerning the capping process: the Alcoa system. It is clearly stated that the removal torque should be between 5 and 14 inch pounds. However, the day of the injury, the records from the manufacturing process of Cott shows that for 16 out of united states oil 24 bottles testes was above the summary recommended interval. The record further indicated that no adjustment was taken to ensure the states imported production was within the specified tolerances. Mary Fisher A Whisper Of Aids? Within the manual, it is states imported oil, also indicated that :”bottles may not be openable by hand. This may result in injury if the closure is improperly removed using a tool or some other devices. “ The judge concludes that Cott has breached the statutory warranties of acceptable quality and fitness. Mary? She also concludes that Cott committed a gross negligence. Therefore according to article 1469, the manufacturer is responsible for bodily, moral and material damages (compensatory damages): Loss of income. In addition, the judges award the united imported oil manufacturer punitive damages or exemplary damages because they released inherently dangerous products and therefore. jeopardizing the safety of the public.

They had to pay to double amount of general damages or compensatory damages (18000) in exemplary damages (36000). University/College: University of Understanding Chimpanzee Chicago. Type of paper: Thesis/Dissertation Chapter. Date: 9 May 2016. Let us write you a custom essay sample on Case1 : King v.BioChem Therapeutic Inc. for only $16.38 $13.9/page.

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