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brains essay 1999 ENSI (Evolution the Nature of university canada, Science Institutes) www.indiana.edu/ This material may be copied only for noncommercial classroom teaching purposes, and only if this source is clearly cited. Essay by Stephen Jay Gould. Wikipedia Davis. NEW NOS TEXT FOR SECONDARY STUDENTS. We now have a textbook for students on the nature of science. Department Mcgill University Montreal Canada. It's intended to replace, or supplement, the inadequate first chapter of your text.

It's designed to coordinate and help sequence several of the nature of science (NOS) lessons on the ENSI site. It is targeted to students in any science class, grades 7-10 (or beyond). It helps to satisfy virtually all the new NOS standards in NGSS and Common Core. If you've used any of ENSI's NOS lessons, you already know how powerful they are. This new book addresses most of the common misconceptions about stanford criteria NOS. It also provides information about the mcgill canada, differences between good science, poor science, and pseudoscience. It offers clues for recognizing those differences, and of tuition at north state university opportunities to practice using those clues.

What's this magic book I've been waiting for all my life? It's called Science Surprises: Exploring the Nature of Science . Tell me more - like where can I see this book? Say no more. It's available as an eBook, published with Smashwords. Click Here to get more information and a link to sample (and purchase) the new eBook Science Surprises. 1. Human values deeply influence science (its terminology, the questions asked, and the criteria for choosing among theories).

2. Bias can be found in scientific studies. 3. Recognizing this, science incorporates procedures intended to eliminate (or at least reduce) the influence of department university canada, natural biases we all have. One of these is the requirement for publication and the process of apartments at ohio, critical peer-review for all such publications. (See also Teaching Strategy #5, below). Department University Montreal Canada. Handout copies of essay by Stephen Jay Gould: Women's Brains (as is, or modified, perhaps with some of his more obscure terms and references explained). See list of university tuition, References below. [If this is not readily available to you, contact the webmaster, requesting a copy of the article be mailed to you. University. Meanwhile, be sure to seriously consider adding some of Gould's publications to your own or your school's, library.] Key to Discussion Questions (and Teacher Notes): end of lesson. Copies of essay by Stephen Jay Gould (as is, or modified) Discussion Questions (end of lesson) Because this lesson provides an excellent opportunity to understand important elements of the Nature of Science , be sure to read our General Background Information , with our Rationale and our Approach, and tips for Presenting the lessons for maximum effect and stanford university Dispelling some of the popular myths about science. In any of the discussions expected with the class, select a few key items (important concepts) that lend themselves to interpretation, and introduce class to the Think-Pair-Share (TPS) routine dealing with those items. Department Of Psychology Montreal Canada. This is how Active Learning is done. 1. In the context of exploring the elements of modern science, it is very important for students to experience at least one example of bias in science.

2. At some point in your unit on the nature of science, hand out copies of the essay, along with the linda new york, discussion questions. Reading can begin in class and of psychology mcgill university montreal canada be continued as a homework assignment. You might want to caution the university of california davis, class to withhold final impressions until they have read the entire article. You might also caution them not to worry too much about the unfamiliar terms and literary references they may encounter. just try to get the essential ideas presented. 3. Next day, be sure to of psychology mcgill montreal, discuss the essay with your class. Be alert for other examples of bias in science; share them with your class, and share them with the webmaster of this site, too! (He will add them to nochlin new york university, this lesson). 4. See the Notes for the Teacher on the KEY page for additional suggestions. 5. Finally, be sure to point out the various ways science makes every effort to counter the influence of bias in its findings: - a. See Concept #3 above; - b. Encourages other scientists to repeat studies, especially if bias or other validity factors are suspected; - c. Mcgill. Uses objective data, quantifiable wherever possible.

As the article attests, even this is no guarantee, but it helps. Athens Apartments. Read this interesting - and ironic - article about the recent claim that S.J. Gould was significantly biased himself in his conclusions that 19th centuray scientist S. Department. G. Athens Apartments. Morton's work (with his measurements of department mcgill montreal canada, about a thousand skulls from people of different races) was influenced by university benefits, his (Morton's) racial biases: By NICHOLAS WADE, June 13, 2011, NY Times, Science Section. Of Psychology Montreal. In a 1981 book, “The Mismeasure of Man,” the paleontologist Stephen Jay Gould asserted that Morton, believing that brain size was a measure of university benefits, intelligence, had subconsciously manipulated the brain volumes of European, Asian and department African skulls to favor his bias that Europeans had larger brains and Africans smaller ones. But now physical anthropologists at the University of Pennsylvania, which owns Morton’s collection, have remeasured the skulls, and in an article that does little to wikipedia of california davis, burnish Dr. Gould’s reputation as a scholar, they conclude that almost every detail of his analysis is wrong. “Our results resolve this historical controversy, demonstrating that Morton did not manipulate his data to support his preconceptions, contra Gould,” they write in the current PLoS Biology. POSSIBLE ALTERNATIVE ARTICLE: Here is an interesting (and perhaps an easier-to-read) article that describes two examples of confirmation bias: N-Rays, and Water Memories (homeopathic remedies). This is written by a practicing scientist (physicist), who also touches on the importance of double-blind experiments where judgment and opinions are involved in the experimental results.

This is a common feature of many pseudosciences, where double-blind tests are either not done, or done poorly. The author also shares his own experience with a new scientific idea, how he (and his team) built a theoretical model of the process, spending most of their time trying to destroy that idea (testing it), and how it was presented to other scientists. Even so, other scientists resisted and critiqued the department mcgill, idea. As a result, his idea became stronger. This is an excellent example of how science is done (as told by a scientist). Cost Of Tuition State University. This process of critical thinking (science) is applied to the claims of climate-change deniers . But once those claims are clearly shown to be false, scientists move on, while the deniers choose to department of psychology mcgill canada, ignore those findings. Wallick New York University. If you use this article, have your students answer and department of psychology university montreal discuss the Discussion Questions that go with it. If you want the key to those 24 questions, contact the webmaster using your school email address.

AN INVESTIGATIVE LAB EXPERIENCE: Therapeutic Touch: Investigating Bias. Athens Apartments University. (Click title to of psychology mcgill university montreal, see the lesson). New York. This investigation engages students in testing for the “placebo effect” in friends and family. Their results are discussed in the classroom. Gould, Stephen Jay. Women's Brains in The Panda's Thumb . 1980. W.W. Norton. Department Of Psychology Mcgill University. Pages 152-159.

Gould, Stephen Jay. University Of Pennsylvania Tuition. The Mismeasure of Man. 1996 W.W Norton. Contains a number of of psychology mcgill university canada, similar examples of bias in science. Apartments At Ohio. Very interesting reading. Some of the ideas in this lesson may have been adapted from earlier, unacknowledged sources without our knowledge. If the reader believes this to be the case, please let us know, and department montreal appropriate corrections will be made. Thanks. 1. Original Source: ENSI sessions (author unknown) 2. Edited / Revised for website by L. Flammer 4/00. by Stephen J. Gould in The Panda's Thumb 1980 (pp 152-159) DIRECTIONS: Read the article, and answer all questions on a separate sheet, in tuition, ink. CAUTION: Be sure to read the entire article before forming your own opinions.

1. (Read pp. Mcgill. 152-155) What is the general point that Gould is presenting in the first 4 pages? 2. What is the general evidence on which that conclusion is apartments university, based? 3. What is the gender of all the department university montreal canada, researchers producing those data and linda nochlin university conclusions? 4. (Read 156-159) What weaknesses or problems with those data and their interpretation does Gould point out? 5. a) Name the one woman anthropologist mentioned who studied the subject of this essay. b) What did she find after proper correction of Broca's data? c) What were her conclusions from that finding? 6. What conclusion does Gould reach about the central issue? 7. Make a general statement about the role of university, bias and assumptions in the collecting, processing, and interpretation of data in scientific studies.

8. What other kinds of bias can you think of that might influence observations and interpretations in science? 9. Describe your initial feelings (about the of pennsylvania tuition, subject, the of psychology canada, author, etc.) after reading the wikipedia, first 4 pages. 10. Describe your feeling after finishing the entire article. ANSWERS TO DISCUSSION QUESTIONS. 1. Women have smaller brains than men, and therefore are less intelligent. 2 Measurements of brain weights and volumes, of both men and mcgill university montreal women. Stanford Criteria. 4. a) very small sample sizes; b) measurements uncorrected for body height, build, age, cause of death; c) influenced by a priori assumptions that women were not as intelligent as men. 5. Department. a) Maria Montessori; b) Women had slightly larger brains than men; c) Women were intellectually superior. men had prevailed due to physical force. Since technology has abolished force as an instrument of power, the era of women may soon be upon us.

6. The whole enterprise of setting a biological value upon groups is. irrelevant and highly injurious. 7. Leslie New York University. This essay describes an example in which bias and assumptions have clearly influenced even the objective collecting, processing, and interpretation of department of psychology canada, data in a scientific study. University Criteria. This was an example of sexual bias, by mcgill montreal, both men and women. 8. Race, nationality, age, sexual orientation, religion, philosophy, political leanings, vested interests (income, reputation, job position, previously published positions, etc.), values, beliefs, experience. 9. [Student impressions] 10. [Student impressions] Notes for of tuition at north carolina university the teacher. Of Psychology. 1. What kinds of reactions do you think this article would produce in your class? 2. Do you think your students could read and understand the essential ideas in this essay?

If not, is there any way you could make it easier? To what extent did the university, literary references and unfamiliar terms detract from the general understanding? [This might be an interesting question to ask in your discussion of the essay.] 3. You might want to provide a glossary of some of the more obscure terms and references if you think they get in department of psychology mcgill montreal, the way of the desired understanding. ------- George Eliot : pen name of well-known woman English fiction writer of the Victorian Age (1819-1880) 4. Alternatively, you could scan or re-type the article, and leave out the more obscure literary references and terms, or replace the terms with more familiar synonyms and explain briefly in context the references. In either case, be sure to indicate this in your reference to the author and source as Modified from. 5. At Ohio. Are you aware of any other articles, perhaps a little easier for students to read, in of psychology montreal canada, which bias clearly plays a role in influencing the work of scientists? [If so, please share them with the webmaster ].

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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 of psychology montreal, 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. Linda New York? In addition, we redacted some applicant-specific information such as contact information, publications in press, and budget specifics. The text of this application is copyrighted. Department Of Psychology Mcgill? You may use it only for linda nochlin university, nonprofit educational purposes provided the document remains unchanged and the PI, the grantee organization, and NIAID are credited. Questions? Contact deaweb@niaid.nih.gov. Department Of Psychology Mcgill? We also offer other outstanding Sample Applications. [Our Web version of university of california davis, this sample application can't reproduce the layout of the actual PDF forms.

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Here are the mba admissions, key fields from that form and the applicant's responses.] Understanding the basis of an immune response that controls infection or provides sterilizing immunity remains a major goal in the search for effective vaccines or immunotherapies for HIV. Department Of Psychology Mcgill? Antibodies (Abs) induced by candidate vaccines to the surface envelope glycoprotein have not neutralized a broad array of primary virus isolates. Wallick New York? For this reason, eliciting a cytotoxic cellular response has been the department university, primary goal in most recent vaccine trials. However, this approach has not been successful in containing viral replication in vaccinees that have become HIV-infected. Antibody-dependant cellular cytotoxicity (ADCC) has been shown to mediate sterilizing immunity against challenge with pathogenic simian immunodeficiency virus [Hessel 2007]. In ADCC, Fc-bearing Abs bind viral epitopes coating an infected CD4+ target T cell and an Fc receptor bearing effector, most commonly natural killer cells (NKs), bind the Ab and use perforin to deliver granzymes which induce apoptosis in the target.

We want to study ADCC in infected patients to understand the magnitude and characteristics of the best responses achieved by natural infection. First, we will compare ADCC mediated by the sera of a cohort of patients using a granzyme B cytotoxicity assay developed in our lab. Based on these findings, we will select the sera of patients with the most ADCC, generate monoclonal Abs (mAbs), and characterize the mAbs based on epitope specificity, affinity, potency, breadth, IgG isotype, and Fc type. We will also evaluate whether ADCC is disparate from classical neutralization. Finally, we will use microscopy to examine the synapse between effectors, Abs, and targets. The outcome of linda university, 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 department mcgill montreal lentiviral infection. University? 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 breadth of antibodies with ADCC activity.

Aim 3 : Characterize the structure and function of the department mcgill, 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 new york, image the functional synapse formed by cellular components involved in ADCC with the goal of defining new goals for the development of HIV vaccines and therapeutics. Gallo RC, Salahuddin SZ, Popovic M. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at of psychology mcgill university montreal, risk for AIDS. New York University? 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 of psychology mcgill canada, risk for linda, acquired immune deficiency syndrome (AIDS). Science. 1983; 220(4599): 868-71. Organization WH.

Global summary of the AIDS epidemic, December 2007. 2007 [cited 2009 September 18, 2009]; Hessell AJ, Hangartner L, Hunter M, Havenith CE, Beurskens FJ, Bakker JM, et al. Fc receptor but not complement binding is important in antibody protection against HIV. Nature. 2007; 449(7158): 101-4. www.hivresearh.org. RV144 Phase III HIV Vaccine Trial Press Release. Department Of Psychology Mcgill Montreal? 2009. Chung A, Rollman E, Johansson S, Kent SJ, Stratov I. The utility of ADCC responses in wikipedia university of california davis, HIV infection.

Current HIV research. 2008; 6(6): 515-9. Kohl S, Starr SE, oleske JM, Shore SL, Ashman RB, Nahmias AJ. Of Psychology Mcgill University Montreal Canada? Human monocytemacrophage- mediated antibody-dependent cytotoxicity to herpes simplex virus-infected cells. J Immunol. University Benefits? 1977; 118(3): 729-35. Forthal DN, Landucci G. In vitro reduction of department montreal, virus infectivity by antibody-dependent cellmediated immunity. Journal of immunological methods. 1998; 220(1-2): 129-38. Cost Of Tuition At North State University? Stratov I, Chung A, Kent SJ. Department? 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. University Benefits Tuition? Journal of immunological methods.

2006; 308(1-2): 53-67. Migueles SA, Osborne CM, Royce C, Compton AA, Joshi RP, Weeks KA, et al. Lytic granule loading of CD8+ T cells is required for HIV-infected cell elimination associated with immune control. Immunity. Department Of Psychology Mcgill? 2008; 29(6): 1009-21. Vago L, Perna SK, Zanussi M, Mazzi B, Barlassina C, Stanghellini MT, et al. Loss of linda nochlin university, mismatched HLA in department of psychology university montreal canada, leukemia after stem-cell transplantation. N Engl J Med. 2009; 361(5): 478- 88. Ziegner U, Campbell D, Weinhold K, Frank I, Rutstein R, Starr SE. Deficient antibodydependent cellular cytotoxicity against human immunodeficiency virus (HIV)-expressing target cells in perinatal HIV infection.

Clin Diagn Lab Immunol. Of Pennsylvania Benefits Tuition? 1999; 6(5): 718-24. Brunetta E, Fogli M, Varchetta S, Bozzo L, Hudspeth KL, Marcenaro E, et al. Department Of Psychology University Montreal Canada? The decreased expression of Siglec-7 represents an early marker of dysfunctional natural killer cell subsets associated with high levels of HIV-1 viremia. Blood. Apartments University? 2009.

Ljunggren HG, Ohlen C, Hoglund P, Yamasaki T, Klein G, Karre K. Afferent and efferent cellular interactions in natural resistance directed against MHC class I deficient tumor grafts. J Immunol. 1988; 140(2): 671-8. De Maria A, Ferraris A, Guastella M, Pilia S, Cantoni C, Polero L, et al. Mcgill University Canada? Expression of HLA class I-specific inhibitory natural killer cell receptors in HIV-specific cytolytic T lymphocytes: impairment of linda nochlin, specific cytolytic functions. Proceedings of the National Academy of Sciences of the department mcgill university montreal canada, United States of America. Leslie New York? 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. Of Psychology University? J Clin Immunol. Wallick? 2001; 21(3): 227-33.

Lambotte O, Ferrari G, Moog C, Yates NL, Liao HX, Parks RJ, et al. Heterogeneous neutralizing antibody and antibody-dependent cell cytotoxicity responses in HIV-1 elite controllers. AIDS. 2009; 23(8): 897-906. Of Psychology Mcgill University Montreal? Dalgleish A, Sinclair A, Steel M, Beatson D, Ludlam C, Habeshaw J. Failure of ADCC to at north carolina university, predict HIV-associated disease progression or outcome in of psychology university, a haemophiliac cohort. Clin Exp Immunol. 1990; 81(1): 5-10.

Koup RA, Sullivan JL, Levine PH, Brewster F, Mahr A, Mazzara G, et al. Antigenic specificity of antibody-dependent cell-mediated cytotoxicity directed against human immunodeficiency virus in antibody-positive sera. J Virol. 1989; 63(2): 584-90. Doria-Rose NA, Connors M. Mba Admissions Criteria? Antibody-secreting B cells in HIV infection. Curr Opin HIV AIDS. 2009; 4(5): 426-30. Burke B, Barnett SW. Department Of Psychology Mcgill Canada? Broadening our view of protective antibody responses against HIV.

Current HIV research. 2007; 5(6): 625-41. Sattentau Q. University Davis? Avoiding the void: cell-to-cell spread of human viruses. Nat Rev Microbiol. 2008; 6(11): 815-26. Chamow SM, Zhang DZ, Tan XY, Mhatre SM, Marsters SA, Peers DH, et al. A humanized, bispecific immunoadhesin-antibody that retargets CD3+ effectors to kill HIV-1- infected cells. J Immunol. 1994; 153(9): 4268-80.

Jolly C, Kashefi K, Hollinshead M, Sattentau QJ. Mcgill Canada? HIV-1 cell to cell transfer across an at north carolina state, Env-induced, actin-dependent synapse. Canada? J Exp Med. 2004; 199(2): 283-93. Nochlin University? 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 department of psychology mcgill, human immunodeficiency virus type 1 between T cells is sensitive to university, entry inhibition. J Virol.

2010; 84(7): 3516-27. Intellectual Support : My mentors Mark Connors and Quentin Sattentau are leading experts in department of psychology mcgill university montreal, their field and have mentored numerous people that have gone on to successful careers in new york university, science. This dual mentorship will teach me to aggressively approach science from two distinctive perspectives in department of psychology mcgill canada, my graduate career, something most PhD scientist don’t experience until their first post-doctoral experience. While at of tuition at north carolina state, 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 of psychology mcgill university canada, NIH/Oxford/Cambridge Scholars Program. While at Oxford I will have the guidance of apartments at ohio university, Lucinda Risius, Managing Director of the Graduate Pathology Program and I will also be assigned a departmental advisor, outside of my lab, with whom I can discuss my research Progress. Educational Resources : Through the FAES at NIH I have access to courses to improve lab specific skills and department montreal canada, foundation knowledge.

I have already participated a Vaccine Development course. At Oxford I will take seminars at nochlin new york university, the Centre for mcgill, Excellence in Teaching and Learning for training in teaching skills. I will also take courses pertinent to my research offered at the Dunn School of Pathology. Both the cost state university, NIH and Oxford have libraries and IT staff that can aid me in scholarly research. Physical Resources : Both labs have sufficient funding to department mcgill montreal, provided me any reagent/equipement need for the proposed research. Lab Space – I am provided with a desk and wikipedia university, personal desktop computer. Bench space is shared within the lab. Safety – In order to ensure our safety from hazardous blood samples we work under laminar flow hoods in of psychology mcgill university montreal, 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 wikipedia university, held in high international regard for its strong teaching and research background and its unique and personal teaching style.

Within the University the Department of Pathology has an excellent reputation for department university, graduate teaching, and at ohio, has achieved 100% success in DPhil graduation within 4 years for the past 3 years. The Department has a strong graduate support structure, in department of psychology mcgill montreal canada, which each student has a principal supervisor, the possibility of a cosupervisor, a departmental advisor, and a college advisor. Athens At Ohio? The supervisor(s) will generally meet with the student multiple times a term, and each of the non-supervisory mentors will meet with the of psychology university, candidate approximately once a term and will file reports on the candidate’s progress. The candidate will be expected to attend a series of high profile external seminars that take place once a week in term time, and a regular series of internal seminars from leading and more junior University and Departmental investigators and students. Athens Apartments At Ohio? Adjoa will attend and participate in the weekly lab journal club, in of psychology university montreal, which scientific papers are taken apart critically by members of the group, and a weekly laboratory meeting in which each lab member presents their ongoing research.

Adjoa will also be encouraged to chat to other members of the department during tea lunch and coffee breaks, a longstanding Oxford institution! The Department has a fully equipped quiet library for literature research and other reading and writing. Adjoa will have her own writing up space close to wallick university, her work bench, equipped with a portable computer and if required, an external screen. Adjoa will have full access to all core facilities, including the imaging suite with multiple light microscopes, a flow cytometry and sorting suite, an electron microscopy facility with full technical and scientific support. We also have strong connections with the department mcgill university, biochemistry and chemistry departments and the Weatherall Institute of Molecular Medicine at cost at north carolina state university, 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. The department has a large, fully-equipped containment-III laboratory shared between two groups, with three tissue culture hoods and associated incubators and ancillary equipment, in which HIV-1 is grown and used to infect cells.

Flow cytometry. The department has a core flow cytometry facility with three BD analyzers (2 x FACScalibur 2 x LSR2) and two sorters. Molecular biology. The Sattentau laboratory has all facilities for of psychology university montreal, molecular biology carried out under containment levels –I, -II and –III. Light microscopy. Linda? The department has 5 confocal microscopes of varying sophistication and resolution, two of which are set up for department montreal canada, 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 new york university, a scanning electron microscope, all of which are maintained and run as a central service facility by department montreal, a skilled dedicated operator. Our collaborator in Oxford (Kay Grunewald) is located at the University Churchill campus, which is 4 miles from the Pathology Department. He maintains and uses 3 microscopes set up for of pennsylvania tuition, 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 department university montreal canada, this sample application can't reproduce the layout of the actual PDF forms. See below for the biographical sketch attachments.]

My interest in studying infectious diseases stems from the 2001 anthrax scare in the Washington D.C. area. I already had a strong interest in science but through my participation in the Gene Search Science Project at Catholic University the following summer I came to university of california davis, understand how medical research impacts treatment for routine illnesses and department of psychology, also plays a role in national defense. Since middle school I have been preparing for a career in linda nochlin university, science. At Eleanor Roosevelt High School I was enrolled in the rigorous Science and Technology Program during which time in participated in the Gene Search Project and researched biochemical pathways that influence sickle cell anemia with Dr. William Winters at university montreal canada, Howard University Hospital. This experience taught me how research and medicine are intertwined and cost at north carolina university, 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 scientific presentations prepared me for a career as a scientist. My lab skills and understanding of department of psychology mcgill, a research career increased exponentially during my four years in linda nochlin, Michael Summers’ lab. Not only department university montreal canada, did I learn about athens apartments at ohio, protein purification, gel electrophoresis, NMR, and ITC while studying MuLV RNA packaging, but more importantly of the time and discipline necessary for department canada, excellent research and university of california davis, the internal drive that keeps one focused. Working with Dr. Nikola Pavletich I learned the value of immediately organizing my data so that others could analyze my results quickly.

In the lab of department of psychology mcgill montreal canada, Tom Cech I had the responsibility of designing a new protocol to study telomerase assembly, a skill that has enabled me to design a novel assay to investigate AIDS specific questions in my graduate studies. University Mba Admissions Criteria? The medical education I’ve received at Columbia has given me a unique perspective with which I approach scientific questions. Under the of psychology university, tutelage of Mark Connors and Quentin Sattentau, leaders in their fields on nonprogressive HIV infection and viral transmission, my understanding of at ohio, infectious disease and my capacity to pursue further research in these fields will be greatly enhanced. Department University Canada? 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 Outstanding Achievement 2006 Goldwater Scholar 2007 UMBC Top Senior Biochemistry Major 2007 Graduated Sum Cum Laude from UMBC 2007 NIH/Oxford/Cambridge Scholar 2010 International AIDS Vaccine Conference Scholarship 2011 Keystone Symposia Underrepresented Minority Scholarship. 2004 Omicron Delta Kappa Leadership Honor Society 2004 Golden Key International Honor Society, Sophomore/Alumni Director 2007 Phi Beta Kappa.

Dey A, York D, Smalls-Mantey A, Summers MF. 2005. Composition and sequence-dependent binding of RNA to the nucleocapsid protein of Moloney murine leukemia virus. Biochemistry. 44(10), 3735-3744. Miyazaki Y, Irobalieva RN, Tolbert BS, Smalls-Mantey A, Iyalla K, Loeliger K, D'Souza V, Khant H, Schmid MF, Garcia EL, Telesnitsky A, Chiu W, Summers MF. 2010. Structure of a conserved retroviral RNA packaging element by NMR spectroscopy and cryo-electron tomography. Leslie New York? J Mol Biol.

404(5), 751-772. Smalls-Mantey A, Winter W. 2003. Biosynthesis of 2,3-diphosphoglycerate in Erythrocytes. Poster presentation at ERHS Science Fair and Prince Georges County Science Fair. March 2003.

Smalls-Mantey A, Dey, A, Phillip C, Summers MF. 2004. Characterization of High-Affinity Nucleocapsid Protein Binding Sites Within the Moloney Murine Leukemia Virus RNA Packaging Signal. Mcgill Canada? Poster presented at cost of tuition at north carolina, 2004 Annual Biomedical Research Conference for department of psychology university canada, Minority Students, November 2004. Smalls-Mantey A, Min J, Pavletich N. 2005. Structural and Biochemical Studies of the Yeast Rad4-Rad23 Complex Bound to DNA.

Poster presented at university, Tri-Institutional Gateways to the Laboratory Program Symposium and 2005 Leadership Alliance. August 2005. Smalls-Mantey A, Miyazaki Y, Summers MF. 2007. Dimerization of department of psychology university montreal, Moloney Murine Leukemia Virus Nucleocapsid Protein Binding Sites Facilitates Binding.

Poster presented at 2007 UMBC Undergraduate Research and Creative Achievement Day. Apartments At Ohio University? April 2007. Smalls-Mantey A, Klein R, Doria-Rose N, Laub L, Rood J, Migueles S, Sattenatu. Department Of Psychology University Canada? 2010. HIV-Specific Antibodies Mediate Rapid Antibody-Dependent Cellular Cytotoxicity Against Primary HIV-Infected CD4+ T Cells. Of Pennsylvania? 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. Of Psychology Montreal? 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. Leslie Wallick New York University? HIV-Specific Antibodies Mediate Rapid Antibody-Dependent Cellular Cytotoxicity Against Primary HIV-Infected CD4+ T Cells.

Poster presented at 2010 NIH/Oxford/Cambridge Scholars Research Colloquium. Smalls-Mantey A, Klein R, Doria-Rose N, Laub L, Rood J, Migueles S, Sattenatu. 2010. HIV-Specific Antibodies Mediate Rapid Antibody-Dependent Cellular Cytotoxicity Against Primary HIV-Infected CD4+ T Cells. Poster presented at 2010 International AIDS Vaccine Conference. September 2010. Smalls-Mantey A. 2010.

Antibody-Dependent Cellular Cytotoxicity and the Control of HIV. Talk given at Frontiers in Biomedicine NIH/Oxford/Cambridge Scholars Program student presentation series. Department Canada? November 2010. [Outside research support redacted from sample.] A. Personal Statement Regarding Project.

Currently HIV-specific ADCC is university mba admissions criteria, considered one of the mcgill, very top priorities in university of pennsylvania, the field of of psychology mcgill university montreal, HIV-specific immunity. Wallick New York University? Our laboratory has assembled the best techniques and department university montreal canada, reagents in leslie wallick new york university, 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 of psychology mcgill university montreal, Pediatrics, The Boston Floating Hospital, New England Medical Center, Boston, Massachusetts 1986 - 1988 Resident in university, Pediatrics, The Boston Floating Hospital, New England Medical Center, Boston, Massachusetts 1988 – 1989 Chief Resident in mcgill university canada, Pediatrics, The Boston Floating Hospital, New England Medical Center, Boston, Massachusetts July 1989 - October 1989 Medical Staff Fellow, Respiratory Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of leslie new york, Health, Bethesda, MD October 1989 - June 1993 U.S. Public Health Service, Research Associate (C.O.), Respiratory Viruses Section, Laboratory of department of psychology mcgill university canada, Infectious Diseases, National Institute of apartments at ohio, Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD July 1993 - June 1994 U.S. Public Health Service, Clinical Associate, Clinical Center, National Institute of Allergy and Infectious Diseases, National Institutes of mcgill university canada, 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 new york, Allergy and Infectious Diseases, Clinical and Molecular Retrovirology Section, Laboratory of Immunoregulation, National Institutes of Health, Bethesda, MD December 2007- Present Chief, HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. Recent Honors and Editorial and Review Board Activities. 2009 - U.S.

Public Health Service Outstanding Service Medal 2009 - present Vaccine Production Development Team Scientific Advisory Board, University of Pennsylvania 2009 - present HIV Enterprise Host Genetics and HIV Diversity Working Group 2010 - present Editorial Board, Journal of department university, Virology. C. Peer-Reviewed Publications. Migueles SA, Sabbaghian MS, Shupert WL, Bettinotti MP, Marincola FM, Schwartz D, Sullivan J, and Connors M. HLA B*5701 is highly associated with restriction of virus replication in of pennsylvania benefits tuition, 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 department university canada, nonprogressors. Nature Immunol 2002; 3(11); 1061-1068.

Migueles SA, Laborico AC, Imamichi H, Shupert WL, Royce C, McLaughlin M, Ehler L, Metcalf J, Liu S, Hallahan CW, and Connors M. The differential ability of HLA B*5701+ long-term nonprogressors and progressors to restrict HIV replication is not caused by wikipedia university of california, loss of recognition of autologous viral gag sequences. J Virol 2003; 77(12); 6889-6898. Iyasere C, Tilton JC, Johnson AJ, Younes S, Yassine-Diab B, Sekaly RP, Kwok WW, Migueles SA, Laborico AC, Shupert WL, Hallahan CW, Davey RT Jr., Dybul M, Vogel S, Metcalf J, and Connors M. Diminished proliferation of HIV-specific CD4+ T Cells is associated with diminished IL-2 production and department of psychology mcgill university montreal canada, recovered by exogenous IL-2. J Virol 2003; 77(20); 10900-10909. Of Tuition At North University? Tilton JC, Luskin MR, Johnson AJ, Manion M, Hallahan CW, Metcalf JA, McLaughlin M, Davey RT Jr., and Connors M. Department Of Psychology Mcgill University Canada? Changes in paracrine IL-2 requirement, CCR7 expression, frequency, and cytokine secretion, of HIV-specific CD4+ T cells are a consequence of stanford, 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 of psychology montreal canada, Connors M. Cost Of Tuition At North University? 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. Department Mcgill Canada? 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. University Criteria? Doria-Rose NA, Klein R, Daniels M, O'Dell S, Nason M, Lapedes A, Bhattacharya T, Migueles S, Wyatt RT, Korber BT, Mascola JR, Connors M. Breadth of HIV-Specific neutralizing activity in sera: clustering analysis and association with clinical variables. J Virol 2009 84(3): 1631-1636. Doria-Rose NA and Connors M. Antibody-secreting B cells in HIV infection. Curr Opin HIV AIDS 2009 4:426-430 Wu X, Yang ZY, Li Y, Hogerkorp CM, Schief WR, Seaman MS, Zhou T, Schmidt SD, Wu L, Xu L, Longo NS, McKee K, O'Dell S, Louder MK, Wycuff DL, Feng Y, Nason M, Doria-Rose N, Connors M, Kwong PD, Roederer M, Wyatt RT, Nabel GJ and of psychology university canada, Mascola JR. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1.

Science 2010 329:856-861. Cost At North State University? Migueles SA and Connors M. Long-term nonprogressive disease among untreated HIV-infected individuals: clinical implications of understanding immune control of department of psychology, HIV. JAMA 2010 304:194-201. [Redacted publication in press] The research direction of the HIV-Specific Immunity Section of the Laboratory of Immunoregulation is focused upon mechanisms of immunity to HIV. The laboratory is staffed by university of pennsylvania benefits, PhD and MD scientists with extensive experience in the humoral or cellular immune response to HIV. Of Psychology Montreal Canada? In addition we have close collaborations with investigators at the NIAID Vaccine Research Center in the area of structure-function relationships of of pennsylvania benefits tuition, HIV-specific antibodies. Our laboratory is well equipped with multi-laser flow cytometers, automated magnetic sorters, and of psychology montreal, imaging equipment to athens apartments university, carry out this project.

Our laboratory is supported by the research budget of the Division of Intramural Research. Over the past 4 years we have received supplemental funding from the Intramural AIDS Targeted Antiretroviral Program (IATAP). Department Of Psychology Mcgill? This will continue for the next 2 years. We have also received funding from the Office of AIDS Research for work on the humoral response to wallick university, 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 Pathology, University of department of psychology canada, Oxford, Oxford UK. Other Experience and Professional Memberships. 1995 - Member, American Association for the Advancement of Science 1998 - Member, American Society for Microbiology 1998 - Member, British Society for Immunology, UK 1998 - Member, Society for wikipedia of california davis, General Microbiology, UK 2005 - Member of the Pasteur Institute Paris France Scientific Evaluation Committee. 2005 - Member of the department of psychology university, Vaccine Research Center (VRC) NIH Board of Scientific Councilors 2007 - Member of nochlin new york university, BMGF Vaccine Monitoring Centre SAB 2008 - Member of NIH HIVRAD/Novartis Neutralizing Antibody Vaccine Consortium SAB 2009 - Member of study section for Swedish Program for International Development 2010 - Member of NIH study section for the B cell Immunology Partnership Program for HIV-1 Vaccine Discovery (U19) C. Selected Peer-Reviewed Publications. Most relevant to the current application. Martin N, Welsch S, Jolly C, Briggs JA, Vaux D and Sattentau QJ. Of Psychology University? (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. Mba Admissions Criteria? (2010) SDF-1/CXCL12 production by mature dendritic cells inhibits the propagation of department montreal, X4-tropic HIV-1 isolates at the dendritic cell-T-cell infectious synapse.

J Virol. 84:4341-51 Groot F, Welsch S and Sattentau QJ. (2008). Efficient HIV-1 transmission from nochlin new york university macrophages to department of psychology mcgill university montreal, T cells across transient virological synapses. Blood 111: 4660-4663. Sowinski S, Jolly CJ, Berninghausen O, Purbhoo, MA, Chauveau A, Kohler K, Oddos S, Eissmann P, Brodsky FM, Hopkins C, Onfelt B, Sattentau QJ and Davis DM (2008).

Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission. Nature Cell. Biol. 10: 211-219. Jolly C and Sattentau QJ (2007).

HIV-1 assembly, budding and cell-cell spread in T cells takes place in tetraspanin-enriched plasma membrane. Benefits Tuition? J. Virol. 81:7873-7884 Jolly C and department of psychology mcgill canada, Sattentau QJ (2007). Adhesion molecule interactions facilitate human immunodeficiency virus type-1-induced virological synapse formation between T cells. J. Virol. 81: 13916-13921. Jolly C, Mitar I and Sattentau QJ (2007). Requirement for stanford mba admissions, an intact actin and tubulin cytoskeleton for of psychology mcgill, efficient HIV-1 assembly and nochlin new york university, spread.

J. Virol. 81: 5547-6 Jolly C and Sattentau QJ. Human Immunodeficiency virus type-1 virological synapse formation in T cells requires lipid raft integrity. J. Virol. 2005 79: 12088-12094.

Jolly C, Kashefi K, Hollinshead M and Sattentau QJ (2004) HIV-1 cell-to-cell transfer across an Env-induced, actin-dependent synapse. Of Psychology University Montreal? J. Exp Med. 199: 283-193. Additional recent publications of important to the Field (in chronological order) Wegmann F, Krashias G, Luhn K, Laamanen K, Vieira S, Jeffs SA, Shattock RJ and Sattentau QJ (2011) A novel strategy for inducing enhanced mucosal HIV-1 antibody responses in stanford, an anti-inflammatory environment. PlosOne 6: e15861. Kong L, Sheppard N, Stewart-Jones G, Robson CL, Chen H, Xu X, Krashias G, Bonomelli C, Scanlan CN, Kwong PD, Jeffs SA, Jones IM, Sattentau QJ (2010) Expression system-dependent modulation of HIV-1 envelope glycoprotein antigenicity and immunogenicity. J. Mol. 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. University? (2010).

Potent adaptive immune responses induced against HIV-1 gp140 and influenza virus HA by a polyanionic carbomer. Criteria? Vaccine 28: 2482-2489. Zanetti G, Briggs JAG, Grunewald K, Sattentau QJ and department mcgill university, 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 this sample application can't reproduce the layout of the davis, actual PDF forms. The attachments are included below. Mcgill University Montreal? 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 wikipedia university of california, the search for effective vaccines or immunotherapies for department of psychology canada, HIV. Antibodies (Abs) induced by athens at ohio, candidate vaccines to of psychology montreal, 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]. At North? In ADCC, Fc-bearing Abs bind viral epitopes coating an department of psychology mcgill, infected CD4+ target T cell and an Fc receptor bearing effector, most commonly natural killer cells (NKs), bind the Ab and use perforin to deliver granzymes which induce apoptosis in the target. We want to study ADCC in infected patients to understand the magnitude and characteristics of the best responses achieved by natural infection. First, we will compare ADCC mediated by the sera of a cohort of patients using a granzyme B cytotoxicity assay developed in our lab. Based on these findings, we will select the wallick new york university, sera of patients with the most ADCC, generate monoclonal Abs (mAbs), and characterize the mAbs based on epitope specificity, affinity, potency, breadth, IgG isotype, and Fc type.

We will also evaluate whether ADCC is disparate from classical neutralization. Finally we will use microscopy to examine the synapse between effectors, Abs, and targets. The outcome of this research will provide insight into the characteristics of Abs that mediate ADCC that are likely important goals in the design of HIV vaccines or immunotherapies. Hypothesis: Antibody-dependent cellular cytotoxicity (ADCC) is department mcgill university montreal canada, a function that has been shown to linda nochlin new york university, mediate protection from lentiviral infection. We hypothesize that variations in ADCC activity of sera are dictated by department mcgill, the amount, specificity, and subclass of HIV-specific antibodies. Aim 1 : Characterize the potency of sera of athens apartments at ohio university, HIV-infected individuals in department mcgill canada, ADCC. In ADCC, Abs bind viral epitopes that are presented by infected CD4+ T cells. NKs expressing an Fc receptor bind the stanford, Fc domain of the Ab and department university, use perforin to deliver granzymes to of pennsylvania benefits, the HIV-infected cell.

Subsequently, granzymes induce apoptosis within the cell. Our lab has developed a flow cytometric assay that measures granzyme B delivered to an HIV-infected CD4+ target T cell. Department University Montreal? We will classify ADCC by the percent of new york, target cells receiving granzyme and the elimination of department university canada, targets as defined by athens at ohio, residual percent of targets expressing p24, HIV capsid. Compare the serum of HIV+ individuals with various rates of progression and viral loads to of psychology montreal, determine which contain Abs capable of mediating the highest levels of ADCC. Compare the ADCC and neutralizing activity of patient sera. Aim 2 : Characterize the apartments university, 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 department of psychology, specific epitopes is required for ADCC. Define the breadth of the polyclonal sera by of pennsylvania tuition, its ability to mediate ADCC in CD4+ T cells infected by different clades of HIV.

Titer serum total IgG, IgG1, and IgG3 binding infected CD4+ T cells. Aim 3 : Characterize the department canada, structure and function of the target-effector synapse. Using both fixed and live cell laser scanning confocal microscopy (LSCM), transmission electron microscopy (TEM) and criteria, cryo-electron microscopy (cryo-EM) and tomography, we will examine the synapse formed between NK and other cells with potential ADCC activity (macrophages and neutrophils) and infected target cells. Of Psychology Montreal? We will specifically investigate: The structure of a functional ADCC synapse. The kinetics of ADCC function in real time and its relation to antibody type and specificity. A role for antibody-dependent cell-mediated phagocytosis (ADCP) in elimination of HIV-infected cells. d. Receptors and 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 of california davis, 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 department of psychology university, 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 a much earlier point in development with smaller numbers of leslie university, participants. Over the past 20 years, research into correlates of immunity to HIV have largely focused on CD8+ cytotoxic T lymphocytes (CTLs) or neutralizing antibodies (NAbs). In addition to neutralization, antibodies (Abs) may fight viral infections by antibody-dependent cell-mediated phagocytosis (ADCP) or by antibody-dependent cellular cytotoxicity (ADCC). Department Montreal Canada? In ADCC, Abs bind viral epitopes presented on infected target cells and Fc? receptor-bearing effector cells such as natural killer cells (NKs) recognize and bind the university tuition, 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 department mcgill canada, field following two important studies highlighting its potential importance in providing immunity to nochlin, HIV.

A recent study by Burton and colleagues demonstrated that neutralizing Abs with mutated Fc? receptor binding regions were less effective in protecting macaques from HIV whereas Abs with impaired complement binding conferred protection to macaques, suggesting that ADCC may be more important in preventing infection than neutralization or complement activation alone 4. Prior to this study, it was widely accepted that infection of a single cell would lead to department montreal, integration and chronic infection. However, because ADCC mediated effects are on virus infected cells and not free virions, this study provided indirect evidence and proof of the concept that ADCC can eliminate lentivirus-infected cells in vivo. In addition, some recent data in human efficacy trials has also greatly increased interest in ADCC as an important component of vaccine induced immunity to HIV. Wikipedia? 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 department of psychology mcgill university canada, 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 linda nochlin new york university, likely mediated through ADCC 5. University Montreal? Our laboratory is part of a large international effort to characterize ADCC antibodies from this trial in order to determine whether there were higher ADCC-mediating antibodies in uninfected vaccinees compared to those that were infected. Although HIV-specific ADCC is now considered an extremely important part of vaccineinduced immunity several basic questions regarding the leslie, nature of an effective ADCC response have not been addressed. For example, the of psychology mcgill university, number, affinity, and specificities of antibodies necessary to mediate ADCC remains poorly understood. Our laboratory has now developed assays that can accurately measure ADCC against HIV-infected cells. We also have assembled panels of monoclonal antibodies from individual patients that permit a characterization of individual antibodies that mediate HIV-specific ADCC.

One of the initial goals of this project was to adapt our current killing assay to provide a more robust assay for HIV-specific ADCC. Past studies of ADCC have been hampered by the availability of assays that are only partially quantitative. There are four primary methods that people use to measure ADCC 6. The most prevalent is the chromium release assays (CRA), which is highly variable, does not specifically account for the mechanism of killing, and is insufficiently quantitative 7. Athens Apartments? The ADCVI assay incubates targets, serum, and effectors for of psychology mcgill canada, 24 hours and university, the supernatant is department, applied to the B95-8 cell line for linda nochlin university, 5-7 days. The endpoint is reduction of viral infection of the B95-8 cells 8. University Canada? This method measures inhibition of viral production and subsequent infection but its disadvantages lie in the length of the assay and failure to measure killing of infected cells. Another assay is the intracellular cytokine staining ADCC (ICS-ADCC) assay measures IFN-?, the primary cytokine responsible for the antiviral activity of stanford university mba admissions, many cells including NKs, CTLs, Th1, and dendritic cells 9. The advantages of this assay are that multiple effector functions can be measured and all cells and Abs are from the department of psychology mcgill montreal canada, 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. Of Tuition At North University? While use of protein pulsed targets is a sensitive method, it likely places artificially high amounts of protein on the surface of infected cells, potentially overestimating the efficacy of ADCC. Recently our lab has developed a highly quantitative flow cytometric assay to measure GrB cytotoxicity using primary HIV-infected CD4+ T cells as targets and autologous NKs as effectors. This is an department of psychology university montreal, adaptation of an assay for measuring the of california, 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 department mcgill, produce accurate quantitative and highly reproducible results. In brief, CD4+ T cells are stimulated for 3 days and HIV infected. Autologous, negatively selected NKs are used as effectors. Effectors and targets are labeled with surface dyes so that they can be discriminated. NKs, targets and serum are incubated in the presence of a granzyme cleavable fluorescent substrate.

Granzyme delivery to the target cell and elimination of HIV-infected targets can then be measured by flow cytometry (Figure 1). Cellular GrB content. GrB cleaves GranToxiLux substrate (FITC), indicating the amount of GrB present within a target cell (Pacific Blue). Elimination of HIVSF162-infected cells. Live targets are stained for intracellular HIV capsid, p24 (PE). Leslie Wallick? Some infected cells show downregulation of CD4 (PE-Cy7). A reduction in department canada, the number of p24 stained cells is represented as Infected Cell Elimination (ICE) and is an indication of cell death. In the example above, ICEInfected+Effectors+Serum = [(58.2-25.8)/58.2] x 100 = 54.9%.

There are several advantages to this assay over older assays that use mismatched cell lines. Because NKs lyse target cells in new york university, the context of MHC mismatch and mcgill, cause nonspecific killing, autologous cells are used in our assay to reduce background. University Davis? 12. In addition, because NK function is diminished in of psychology mcgill, HIV-infected patients, we use the NK cells and linda nochlin university, CD4+ T cell targets from uninfected patients in our assay as a readout for the effectiveness of department of psychology montreal canada, a given serum sample in mediating ADCC 13, 14. We observed variations in NKs from normal individuals in their ability to mediate ADCC and choose donors that provide optimal signal to noise ratio that we will use to apartments at ohio university, compare the serum of HIV+ individuals (Figure 2). The targets used in this assay are likely closer to department of psychology mcgill university montreal, the in vivo situation given autologous HIV-infected targets are used in the place of antigen pulsed cell lines.

Other advantages include our assay’s ability to measure the mechanism of ADCC (granzyme delivery) and the outcome (death of infected cells) (Figure 2). MHC-1 is down-regulated in university of pennsylvania tuition, virally infected cells, and the loss of MHC-mediated killer inhibitory signals permit NKs to kill a cell 15, 16. We control for this by measuring the granzyme content of targets that are incubated only with effectors and sera from HIV-uninfected volunteers. For a positive control we are using a novel anti-CD3 Ab that will mediate ADCC to canada, all CD3-bearing targets (Figure 3). With this Ab we have already demonstrated (1) the new york, 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 of psychology mcgill university canada, ADCC in HIV infected individuals . Rational : There is considerable controversy regarding the magnitude of ADCC activity in sera from HIV+ individuals and how it correlates with disease progression.

It has been suggested that sera from elite controllers exhibit greater ADCC activity which correlates with CD4+ T cell count 17, 18 while others have sighted no correlation between ADCC and athens apartments at ohio, disease progression 19, 20.We will compare the serum of HIV+ individuals with various rates of progression and department of psychology mcgill montreal canada, viral loads to determine which contain Abs capable of mediating the highest levels of ADCC. We will also compare the ADCC and stanford university criteria, neutralizing activity of patient serum to evaluate whether or not ADCC and neutralization always occur together in polyclonal sera which is yet to be determined 21, 22. Methods : Over the past several years, in collaboration with the Vaccine Research Center (VRC) our laboratory has focused upon recruiting HIV-infected patients with broadly crossneutralizing antibodies. 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 university canada, compare multiple indicators of immunity with ADCC. Expected Outcomes/Interpretation : Based on in vitro and passive transfer macaque studies, we expect LTNPs to leslie wallick, exhibit greater ADCC than progressors. Of Psychology Mcgill Montreal? Our current knowledge attributes LTNP delayed progression to superior CTL cytotoxicity but our data may show ADCC also to be a significant factor 11. Potential Complications : We do not foresee any difficulties in accomplishing this objective. Aim 2: Characterize MAb from serum identified as having potent ADCC activity with regard to university benefits tuition, 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 department of psychology mcgill, ADCC. Wikipedia? An ideal HIV vaccine would be able to protect against department canada diverse virus strains so it is university mba admissions, important to determine whether Abs raised against one clade of virus would be able to mediate ADCC in CD4+ T cells infected by of psychology canada, different clades. We will use multiple strains of virus from clade A/E, B, and C to infect CD+ T cells and criteria, compare killing of of psychology university, target cells in linda nochlin new york, the presence of department of psychology mcgill montreal canada, serum pooled from clade B HIV+ patients. IgG1 and IgG3 are the leslie new york university, predominant IgG isotypes with roles in ADCC. It is department of psychology canada, possible that variations in benefits tuition, ADCC activity of sera are mediated by variations in IgG subclass. We will use infected CD4+ T cells, apply sera with various levels ADCC at the same dilutions used in our killing assay, and mcgill university canada, measure total bound IgG, IgG1, and at north carolina state university, IgG3 by flow cytometry. We believe flow cytometry is a better way of of psychology mcgill montreal, measuring titers of binding Abs as compared to ELISA because Abs will recognize all possible epitopes on the surface of an new york, infected cell in their natural conformation. Expected Outcomes/Interpretation : Determining the association between ADCC activity and IgG subclass may provide insights into the necessity of eliciting a specific class of IgG via particular antigens and adjuvants. Potential Complications : We now have robust assays for subclass binding and do not expect complications with this portion of the project.

Aim 3: Evaluation of the mcgill university montreal, target-effector synapse. Rational : Using microscopy to study ADCC is important because it will help us define structural and 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 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 stanford university mba admissions criteria, undergoing lysis and by 24 hours all targets had been lysed. However, the bispecific antibody may not be representative of ADCC with naturally occurring HIV-specific antibodies. Mcgill University Canada? In addition, the structure of the NK to nochlin, HIV-infected target synapse was not examined. Methods : The lab of Quentin Sattentau has focused on examining the synapse of cells involved in department of psychology university canada, HIV infection. They were the wikipedia of california davis, first to demonstrate HIV-1 spread between T cells via virological synapses and of psychology university, nanotube structures for viral transmission between CD4+ T cells 25. They have recently demonstrated that macrophages can infect CD4+ T cells every 6 hours and that cell-tocell transfer of virus is 10-fold more efficient than free virus spread 26.

To study the stanford university criteria, kinetics of department montreal canada, ADCC in of pennsylvania tuition, real time we will use time-lapse laser scanning confocal microscopy (time-lapse LSCM). Cell populations will be negatively selected from mcgill canada PBMCs using magnetic cell sorting. HIV-infected CD4+ T cells will be mixed with patient serum or Abs of multiple specificities (see Aim 2) and NKs to evaluate ADCC; or neutrophils/monocytes to evaluate antibody-dependent cell-mediated phagocytosis (ADCP) and applied to poly-L-lysine coated cover slips. Cover slips will be fixed in paraformaldehyde, quenched with NH4Cl, permeabilized with Triton-X, and stained for wallick, granzyme B, IgG, CD4/CD16/CD14 with fluorescent probes. After mounting, images will be acquired every minute for 6 hours using a Zeiss Pascal Axivert 200M scope.

We will use transmission electron microscopy and tomography (TEM) to department university montreal canada, generate higher resolution static images of the ADCC functional synapse. For TEM targets, serum, and effectors will be incubated for approximately 1 hour, fixed in paraformaldehyde and glutaraldehyde, and stained with osmium tetroxide. Samples will be embedded in epoxy resin, cut, and imaged using a 300kV FEI Technai TF30 27. If necessary cryo-EM will also be used for structural studies with the aid of Oxford collaborator Kay Grunewald. These experiments will be completed using the pathology department’s core bioimaging facility and I will take department’s Advanced Light Microscopy and Electron Microscopy course in preparation for this research. Expected Outcomes : We expect to wallick, elucidate the kinetic and functional relationship between ADCC components and answer questions such as what density of Env epitopes are needed to recruit effectors, how many effectors are recruited per of psychology university montreal target. We do not foresee any difficulties in accomplishing this objective. The results of these studies will include novel MAb with possible therapeutic value; a new tool for the study of ADCC with potential utility for HIV vaccine trials; and increased understanding of basic HIV immunology. In the wake of the RV144 trial, ADCC has become a major focus in university of california, the field of HIV-specific immunity. We are very well positioned to carry out these important studies because of our large collection of cells, sera, and detailed clinical data from patients that are part of the NIAID HIV clinic, and both labs’ extensive experience in this area.

Samples are collected under the NIAID IRB-approved protocol 02-I-0086. Protections for mcgill university montreal, human subjects are in stanford university mba admissions criteria, accordance with NIAID Division of Intramural Research policies. Phlebotomy may cause some discomfort, and occasionally some bleeding or bruising at mcgill montreal canada, the site. Benefits Tuition? On rare occasions, people faint while having blood drawn. Blood drawing will not exceed 150 milliliters (30 teaspoonfuls) on any day or visit. In the course of any time frame during this study, the total amount of blood will not exceed 10.5mL/kg, or 550 milliliters over any 8-week period, which is within the safety guidelines for blood drawing practiced at the Clinical Center. Like standard phlebotomy, leukapheresis is department of psychology university montreal, occasionally associated with local bleeding and bruising at the site of needle insertion.

Lightheadedness can also occur, and people faint on wallick new york, rare occasions. Occasional tingling in the arms and legs can occur with the procedure and 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 up to 450 milliliters. Trained medical personnel who are equipped to deal with any of these potential problems will always be on hand during the procedure. Inclusion of Women and Minorities. Gender, Ethnicity and Race Consideration. This study involves techniques and department, 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 at ohio, pool of patients that receive care in Clinics 8 at the NIH Clinical Center. Patients will be recruited from outside the NIH community by advertisements posted in the Clinical Center, the NIAID web site, and advertised in of psychology canada, other media. We will attempt to facilitate minority recruitment using existing NIAID community outreach efforts involving local clinics in the Washington, DC metropolitan area. In adult HIV-infected patients planning to interrupt HAART, patients will be fully counseled prior to entry into the study as to the potential risks of discontinuing HAART therapy and the potential benefits of continuing HAART therapy, in of tuition at north carolina state university, 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 department university, the study. Patients stopping HAART therapy will be monitored closely for virologic and of tuition at north carolina, immunologic relapse and will be offered therapy, based upon of psychology mcgill canada, the algorithm for safety outlined above. Target enrollment for this study is 300 individuals and is currently ongoing. Inclusion of criteria, Children (and Pregnant Women) Inclusion of Children and Pregnant Women. This study will be confined to HIV-infected adults greater than or equal to mcgill university montreal, 18 years of age.

As an observational study there is no therapeutic benefit or clinical intervention resulting from participation in this trial, thereby children are not being denied the potential benefits of leslie new york, a research intervention. We also do not have the historical research database and in vitro findings on HLA linkages with LTNP in the pediatric population to make valid comparisons within that cohort. The potential risks of department of psychology mcgill montreal, 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 cost of tuition at north carolina state university, address this topic, should preliminary results from this study warrant further evaluation in the pediatric population. The safety of discontinuing antiretroviral therapy has not been established during pregnancy and nursing, and current guidelines continue to advise HIV-positive women to take antiretroviral therapy to of psychology university montreal, prevent viral transmission to the child during that time period. Therefore, pregnant or nursing women will be excluded from this study. Any woman of childbearing potential must have a negative pregnancy test within two weeks prior to study entry. All participants who engage in heterosexual intercourse must use two forms of reliable birth control for the duration of the study. When I entered the NIH/Oxford/Cambridge Scholars program I identified Mark Connors and Quentin Sattentau as two HIV researchers with whom I would like to train with because of their focus on of tuition at north carolina university, HIV immunology, vaccine design, and department mcgill university, their expertise in benefits tuition, basic immunology techniques, flow cytometry, and microscopy. I initiated contact between the two individuals and they agreed to start a collaborative project with me. After studying NAbs with Mark Connors for one summer I decided I wanted to focus on antibodies that mediate ADCC.

I outlined the facets of ADCC I wanted to investigate then received feedback from both mentors. I subsequently wrote the department of psychology university montreal canada, proposal that was edited by both mentors and wikipedia, 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 of psychology university montreal, meet at conferences. Nochlin? Communication will continue in the same manner while I am in Quentin Sattentau’s lab.

Selection of Sponsors and of psychology university montreal canada, Institution. Selection of Institution. I decided to join Columbia’s MSTP program because of its tradition of exemplary medical education, medical research, and unparalleled support offered to students from program administrators. Because of my previous research experience with HIV I knew I wanted to nochlin, continue research in this field. I decided to join the NIH/Oxford/ Cambridge Scholars Program to complete my dissertation research because it would provide me access to a more extensive network of scientists than Columbia could. Oxford has a particularly strong network of HIV investigators and the structure of its graduate program allows for a particularly specialized education. As a graduate student in the pathology department I am allowed to select seminars and accelerated 1-day to 1-week courses that allow me to attain skills quickly and immediately implement them into my research. In addition, the NIH/Oxford/Cambridge Scholars program provides funding for students to take courses offered by any institution giving me access to mcgill canada, virtually any educational opportunity necessary. In addition, through NIH’s Foundation for Advanced Education in the Sciences I’ve had the opportunity to take courses that will help me towards my goal as in infectious disease investigator such as the Vaccine Development course I completed.

The NIH/Oxford/Cambridge Scholars Program is designed so that students work with a mentor at NIH and one at wikipedia, a university. Department Mcgill Montreal? 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. Apartments At Ohio University? Quentin Sattentau was studying how to elicit effective anti-HIV neutralizing Abs (NAbs) for vaccines and mcgill montreal canada, adjuvants to apartments university, stimulate systemic and mucosal immunity. Through my search at mcgill canada, 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 leslie new york, NAbs of long-term nonprogressors (LTNPs) would complement Dr. Of Psychology Mcgill University Montreal? Sattentau’s vaccine development goals.

In addition, Dr. Connors’s unique cohort of LTNPs would provide ready access to samples to study many facets of HIV infection. 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 athens apartments, suited to me as a future MD/PhD researcher.

I will follow the principles on responsible conduct of research as outlined in department canada, NOT-OD-10- 019. As an undergraduate at UMBC I took a semester-long course entitled “Ethics/Integrity in Scientific Research” which first help me to understand the apartments university, responsibility scientists have to department university canada, one another and medical community honestly share information. As a Columbia medical student, I have taken the university, Hippocratic Oath to guide my patient care and department of psychology mcgill, I am expected to adhere to the code of ethics as outlined in student handbook. Upon joining the NIH I took an of pennsylvania tuition, 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 department of psychology mcgill university montreal, Research Ethics”. Since I will have access to sensitive patient data it is essential that I maintain the confidentiality of these individuals. When I started research at cost of tuition carolina, NIH I participated in a patient confidentiality seminar. Department Mcgill University Montreal Canada? Oxford offers an “Ethics: Confidentiality” course in which I will enroll to better my further my understanding and wikipedia, ability to maintain ethical practices with regards to research.

As a physician, I hope to alleviate an individual’s immediate suffering; and as a scientist I hope to contribute to long-term solutions that can prevent suffering. To work most effectively at the interface of medicine and university montreal canada, science, I have endeavored to earn an MD/PhD. Leslie Wallick New York University? I believe that the department of psychology mcgill montreal, 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 leslie university, improving the montreal canada, quality of life. A few years ago I conducted research on of tuition, telomerase, an enzyme that maintains healthy chromosome length. When telomerase is upregulated, as it is in 90% of carcinomas, cells can propagate indefinitely. When telomerase levels are halved, a bone-marrow failure disease called Dyskeratosis Congenita (DC) results. While looking at yeast cells with low levels of mcgill university montreal canada, telomerase and measuring their growth rates, I noticed two things. The first was that cells with low levels of telomerase grew slowly. Wikipedia Davis? Secondly, these cells had abnormal morphologies, as do tumor cells. These observations led me to wonder whether the progression of cancer in individuals with DC was slower than in mcgill canada, patients without it because DC patients have less active telomerase. Upon discussing this with my P.I., he acknowledged having never considered his research from that aspect.

A literature search demonstrated a lack of any substantial research concerning this question. Research in biochemistry affords many new advances in medicine, but through that experience the athens university, importance of of psychology montreal canada, keeping a broader medical picture in linda nochlin university, mind became clear to me. My goals as a physician scientist are to treat patients and of psychology mcgill canada, conduct research that will allow me to impact patients I will never meet through therapeutic discovery; specifically serving as a creative link between science and medicine in the field of infectious disease. The training I will receive in Oxford’s doctorate program will prepare me to be a competitive investigator through a tailored curriculum, expert dual-mentoring, learning to work in a collaborative environment, and by giving me extensive writing experience via paper submissions and even through this grant. These are all specific skills that would be harder and take longer for me to university, garner through a traditional medical student experience. The advantage I have in understanding that I want to be a physician-scientist has given me the opportunity to carefully cultivate these skills early in my career. Activities Planned Under This Award. Research 80%, Seminars/Courses 10%, Presentation/Career Development/Clinical 10% Research Skills : While working in Mark Connors’s lab I have acquired specific skills such to creatively study immunology such as learning to use flow cytometry. I discuss my research progress frequently during the week with Dr.

Connors. We also have phone conferences and meet with Dr. Sattentau at of psychology montreal canada, numerous conferences throughout the year. Writing Skills : When I entered the program I took a grant-writing workshop sponsored by the NIH Graduate Partnership Program. I also completed a 3-day grant-writing course during my senior year of college. I will improve my writing skills through preparation of manuscripts based on my research to be submitted for publication, applying for training grants, and of pennsylvania tuition, 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. Department Mcgill University Montreal? I attend weekly seminar series hosted at athens apartments, the NIH such as the Wednesday Afternoon Lecture Series, Immunology Interest Group seminar series, and weekly lab meetings.

Bench to of psychology mcgill university montreal, bedside clinical training : I will attend the linda nochlin new york, Clinical Research Training Program (CRTP) weekly rounds. I will also have the opportunity to be mentored by an infectious disease clinician. Presentations : I will continue to annually attend and present at pertinent Keystone Symposia and the Annual AIDS Vaccine conference. Montreal? I have also had opportunities to present posters at the NIH/Oxford Cambridge Scholars Program Colloquium and the Oxford Pathology Graduate Student Symposium. I have given a talk to my graduate program journal club and will have more opportunities to present my research in lab meetings.

Career Development : The NIH/Oxford/Cambridge Scholars programs hosts a seminar series where leaders in government/academic research, the pharmaceutical industry, and finance speak with us about their career. I also attended NIAID Fellows retreat that focused on of pennsylvania tuition, career development. Teaching : As I prepare to mcgill university montreal, leave the stanford university, lab I will be responsible for training a new research fellow. Year 1 (continued) and of psychology university, 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 of california, manuscripts based on my research to be submitted for publication and department university, writing reviews. I will complete the new york university, following 1-day courses offered at of psychology montreal, Oxford: Writing Skills – Paper and Thesis; Doctoral Thesis Writing, Discipline specific learning : I will participate in courses and Skills Workshops offered by university of pennsylvania tuition, Oxford including “Advanced Light Microscopy,” “Electron Microscopy,” and “Introduction to Statistics.” Bench to of psychology mcgill, bedside clinical training : I will attend the Nuffield Department of Clinical Medicine Grand Rounds and shadow an infectious disease clinician. Career Development : See above. New York? 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 mcgill university, Oxford course “Teaching and university, Learning Skills” to prepare myself. Year 3 and Year 4: Medical School (Columbia) In the of psychology mcgill canada, summer after 11th grade I participated in the intensive 6-week Gene Search Program at the Catholic University of university of california, America that introduced me to molecular biology and mcgill montreal, the exciting race to sequence the human genome.

That summer, I learned much more than how to run a gel; I learned to read and comprehend primary research articles and linda new york university, how to design experiments. Because of my accomplishments that summer, I was invited to 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. Canada? 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 athens at ohio, oxygen, thereby facilitating oxygen release to of psychology mcgill montreal, tissues. Patients suffering with sickle cell anemia have high levels of 2,3- DPG. University? While this effect may seem advantageous to patients with sickle cell anemia, deoxygenating hemoglobin ultimately causes red blood cells to of psychology mcgill university montreal canada, 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 of pennsylvania, measure a by-product of the 2,3-DPG pathway. An exciting therapeutic prospect of our research is montreal canada, 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 cost of tuition at north state university, a five-chapter thesis, in department of psychology mcgill montreal canada, accordance with my high school’s Science and Technology Program, and linda new york university, presented it at mcgill canada, my school’s science fair, where I was awarded third place in wallick university, biochemistry. During college I spent four years working with Dr. Michael Summers to department university canada, investigate Moloney Murine Leukemia Virus (MuLV) dimerization. Of Tuition Carolina? Understanding dimerization is key to mcgill university montreal canada, developing gene and antiviral therapies. MuLV is similar to HIV in that it is a retrovirus that packages two copies of apartments university, its RNA genome.

Packaging of dimerized RNA is mcgill university, mediated by interactions between the nucleocapsid (NC) domain of the assembling Gag polyproteins and a specific domain of the RNA called the Psi-site. Linda Nochlin New York University? Previous work in mcgill university montreal, the Summers lab suggested a riboswitch mechanism for of tuition at north state, MLV genome packaging, where, in monomeric RNA, Psi-site UCUG segments capable of binding NC are sequestered by base pairing, but upon department of psychology canada, dimerization, become exposed to bind NC. My project was to investigate whether similar sequences in the Psi-site could also bind NC. Using isothermal titration calorimetry and university of pennsylvania tuition, nuclear magnetic resonance, we identified short RNAs (ACAG, UUUG, and UCCG) that bind NC with nanomolar affinity. Our findings suggest that: 1) binding depends on an unpaired guanosine, 2) binding is enhanced in short RNAs containing terminal phosphates, and 3) binding affinity varies by more than one order of magnitude depending on which three nucleotides lie upstream of the guanosine. The paper I co-authored (Dey, A., et. al., 2005) extends an established model for genome recognition, in university montreal canada, which the university mba admissions, NC domains of assembling Gag molecules interact with multiple X(i-3)-X(i-2)-X(i-1)-G(i) elements (X is a variable nucleotide) that appear to be preferentially exposed in the dimeric RNA. I presented this research at the 2004 ABRCMS and at multiple UMBC symposiums. I continued to investigate potential dimerization and NC-binding regions of the Psi-site using native and mutant MuLV RNA segments in gel-shift assays. As expected from our riboswitch hypothesis, we observed NC binding preferentially to RNA dimers which was also confirmed by department of psychology mcgill, equilibrium dialysis. Most recently our lab published the NMR structure of this dimer (Miyazaki, Y., et al., 2010). During the summer of 2005 I participated in the Weill Cornell/Rockefeller/Sloan Kettering Gateways to the Laboratory Program.

I worked with Dr. Leslie Wallick New York University? Nikola Pavletich toward solving the crystal structure of the Saccharomyces cerevisiae Rad4-Rad23 complex bound to department mcgill montreal, a DNA substrate. New York University? Rad4-Rad23 is a homolog of human XPC-HR23B, a DNA damage-repair protein. In its mutated form, XPC-HR23B causes the disease Xeroderma Pigmentosum. Patients are extremely sensitive to UV-light and develop skin cancer during childhood. 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 department of psychology mcgill university montreal, the 2005 SACNAS National Conference. In 2006 I studied telomerase assembly in stanford university mba admissions, the lab of Dr.

Thomas Cech at the University of Colorado at Boulder. The central role telomerase plays in of psychology university, protecting chromosome integrity places telomerase at the heart of two common human ailments—cancer and aging. To study how and where in the cell telomerase is wikipedia university davis, assembled from its RNA and protein components, we used the budding yeast Saccharomyces cerevisiae as a model organism. University? We sought to davis, understand whether the of psychology canada, noncoding telomerase RNA (TLC1) goes through a cytoplasmic phase during its biogenesis. One model is that a polyadenylated precursor form of TLC1 is exported to the cytoplasm where it associates with Sm proteins. Athens Apartments At Ohio? Mtr10p then plays a role in importing the department of psychology university montreal, TLC1-Sm complex back into the nucleus, where the of pennsylvania benefits tuition, telomerase holoenzyme is assembled. Using cellular fractionation and department of psychology mcgill montreal, real-time RT-PCR, we attempted to university mba admissions criteria, localize TLC1 in its various stages. During the summer between my first and department of psychology mcgill university canada, second year of medical school I joined the university tuition, lab of Mark Connors where I screened patient sera for department university montreal, breadth and potency of neutralizing Abs against leslie wallick university HIV using a TZMBL neutralization assay. We demonstrated that that progressor serum has greater breadth in mcgill university canada, potency in neutralizing HIV than Long-Term Nonprogressors (Doria- Rose, N., et al., 2009). Athens At Ohio University? Studying NAbs peaked my interested in other anti-viral mechanisms mediated Abs and lead to my proposed project of investigating antibody-dependent cellular cytotoxicity.

Each research experience has shown me the many nuances of a research career. University Canada? I learned about: 1) the benefits, importance of basic research in department university montreal, developing medicines, 2) the time, organization, and ingenuity it takes to conduct research, and 3) the vital role that a physician-scientist plays in translating basic research into medical treatment. Leslie? Although I’ve experienced frustrations and department of psychology university, 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 wallick university sample.] QUENTIN SATTENTAU MENTOR STATEMENT. [Redacted from sample.] [Our Web version of this sample application can't reproduce the department canada, 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. New York? The reviewers noted that the mcgill montreal, candidate is outstanding, with a strong record of research training and accomplishment. The candidate appears to wallick university, be highly motivated. Her sponsors, at both institutions, are well qualified to provide the necessary training and the letters of recommendation were uniformly laudatory. Minor weaknesses of the application included the ambitious research plan to of psychology, be accomplished in two years, the risk of conducting the research at two sites, and the failure to address pitfalls and wallick new york university, alternatives of the research project. These weaknesses, however, did not detract from the reviewers’ enthusiasm.

This training project will have a high impact in ensuring that the mcgill university canada, candidate maintains her potential to become an independent clinical researcher. DESCRIPTION (provided by applicant): Understanding the athens apartments, basis of an immune response that controls infection or provides sterilizing immunity remains a major goal in the search for effective vaccines or immunotherapies for HIV. Antibodies (Abs) induced by candidate vaccines to the surface envelope glycoprotein have not neutralized a broad array of primary virus isolates. For this reason, eliciting a cytotoxic cellular response has been the primary goal in most recent vaccine trials. However, this approach has not been successful in containing viral replication in vaccinees that have become HIV-infected. Antibody-dependant cellular cytotoxicity (ADCC) has been shown to mediate sterilizing immunity against challenge with pathogenic simian immunodeficiency virus [Hessel 2007]. In ADCC, Fc-bearing Abs bind viral epitopes coating an infected CD4+ target T cell and an Fc receptor bearing effector, most commonly natural killer cells (NKs), bind the Ab and use perforin to department of psychology mcgill university canada, deliver granzymes which induce apoptosis in the target. We want to wikipedia university of california, study ADCC in infected patients to understand the magnitude and characteristics of the mcgill university montreal canada, best responses achieved by natural infection.

First, we will compare ADCC mediated by the sera of of pennsylvania tuition, a cohort of university montreal canada, patients using a granzyme B cytotoxicity assay developed in our lab. Based on these findings, we will select the sera of patients with the most ADCC, generate monoclonal Abs (mAbs), and characterize the mAbs based on epitope specificity, affinity, potency, breadth, IgG isotype, and Fc type. We will also evaluate whether ADCC is disparate from classical neutralization. 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 stanford criteria, HIV vaccines or immunotherapies. Hypothesis: Antibody-dependent cellular cytotoxicity (ADCC) is a function that has been shown to mediate protection from department montreal lentiviral infection. We hypothesize that variations in ADCC activity of university tuition, sera are dictated by the amount, specificity, and university, subclass of HIV-specific antibodies. Aim 1: Characterize the potency of athens apartments at ohio, sera of HIV-infected individuals in mcgill montreal, ADCC.

Aim 2: Characterize the specificity and breadth of antibodies with ADCC activity. Aim 3: Characterize the new york university, 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 image the functional synapse formed by cellular components involved in ADCC with the goal of defining new goals for the development of HIV vaccines and therapeutics. Fellowship Applicant: 1. Sponsors, Collaborators, and Consultants: 1. Research Training Plan: 2. Training Potential: 1. Institutional Environment Commitment to Training: 2. Overall Impact/Merit : This proposal is from an of psychology mcgill montreal canada, applicant who is currently enrolled in the NIH M.D./Ph.D.

Partnership Training Program and is a participant in the NIH/Oxford/Cambridge Scholars Program, which promotes joint research in an NIH laboratory and in a university research lab. Ultimately, she will receive her Ph.D. from Oxford University and complete her medical training at Columbia University. The applicant is highly recommended by linda nochlin, previous research mentors and has an outstanding academic record. Department Montreal? Her research experience, which includes four years of linda nochlin new york, undergraduate research, is matched by her productivity; she is a contributing author on two published papers and has presented her work at department of psychology mcgill montreal, numerous scientific venues. University Of Pennsylvania Benefits Tuition? The research plan, which derives directly from the expertise and interests of the mentor, focuses on relationships between antibody-dependent cellular cytotoxicity (ADCC) in HIV-1-infected patients, HIV-1-associated disease progression, and antibody subtype. Additional experiments, which will draw on the expertise of the co-sponsor, will investigate the of psychology university montreal canada, target-effector synapse during ADCC. These studies will be significant for their basic science and translational value. The training plan is unique in that training and research will be accomplished in two separate laboratories of the university, sponsor and co-sponsor. This proposal outlines an excellent training opportunity that will greatly benefit the applicant and her potential for establishing an department of psychology mcgill montreal canada, independent research career. The applicant, who is currently enrolled in an M.D./Ph.D. training program, is described in three strong letters of recommendation as enthusiastic, articulate, knowledgeable, highly focused, and cost state university, 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 department of psychology montreal canada, undergraduate research experience, which involved work with the Moloney Murine Leukemia Virus, and wikipedia, research performed during a summer program at the Howard Hughes Medical Institute focused on studies of telomerase. Mcgill University Canada? Technical approaches for which she was trained included cell growth assays, transformation, RT-PCR, isothermal titration calorimetry, NMR, and cost of tuition at north university, cryo-electron tomography. Department Of Psychology Montreal? Through her prior research experience, the mba admissions criteria, applicant has been included as a contributing author on two published papers and has presented eight posters and canada, one oral presentation at various local, national, and athens at ohio, international meetings. The applicant has an mcgill canada, outstanding academic record (3.97 GPA) and numerous awards and recognitions reflecting superior academic performance. The collaborative project outlined in the proposal was an outgrowth of a dialog initiated by the applicant between the leslie, sponsor and co-sponsor. The applicant has provided thoughtful goals for developing a career as both a scientist and physician. 2. Sponsors, Collaborators, and mcgill university montreal canada, Consultants: The applicant’s mentor and sponsor, who is currently Chief of the HIV-Specific Immunity Section in the Laboratory of Immunoregulation, NIAID/NIH, is an new york, established and productive senior investigator with research support provided by the NIH. The co-sponsor is also a productive researcher with a consistent record of support for studies related to HIV/AIDS.

The research interests and expertise of the sponsor and co-sponsor will provide excellent support for the applicant’s research and training. Mcgill University Montreal? The expertise of the co-sponsor will be particularly relevant to studies outlined in Aim 3. The sponsor has trained an average of four students per year over 20 years, suggesting an excellent training environment for the applicant. Similarly, the co-sponsor has trained nine Ph.D. trainees since 2003. 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. University? trainees in mcgill university, the co-sponsor’s laboratory. Davis? The latter trainees will overlap with the applicant for department of psychology mcgill university montreal canada, one year or more. Linda New York University? These interactions will enrich the applicant’s training. The research plan is built on studies of antibody-dependent cellular cytotoxicity in HIV-1-infected individuals. Experiments will examine the potency of sera of HIV-1-infected individuals in university montreal canada, ADCC (Aim 1), the specificity and breadth of antibodies with ADCC activity (Aim 2), and the structure/function of the target-effector synapse that mediates ADCC. New York University? The central feature of the proposed research is a novel and university montreal canada, quantitative ADCC assay (developed in the sponsor’s lab) that offers significant improvements over university other ADCC assays.

Results generated from experiments in Aims 1 and of psychology, 2 will have both basic science and translational value, while results from Aim 3 experiments will provide basic information about the mechanisms of ADCC. The applicant and criteria, sponsors are well positioned to perform these studies, since the patient populations and study procedures are already in of psychology university canada, place. The applicant is participating in university, the NIH/Oxford/Cambridge Scholars Program, which promotes research with a mentor at the NIH and another mentor at a university. Consistent with the university, Scholars Program, the research training plan includes studies and athens apartments at ohio university, 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 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 of psychology university canada, results and teaching. Training at the NIH (sponsor) will be a continuation of the current laboratory work, with increased emphasis on mba admissions, independent research and critical thinking.

Training at Oxford (co-sponsor) will include skills development in experiments involving infectious HIV-1, microscopic imaging, and biochemical and of psychology university montreal canada, serological techniques (such as ELISA, gel electrophoresis, and university of pennsylvania tuition, mass spectrometry). Although the targeted patient enrollment is department university montreal, given as 300 HIV-1-infected individuals, the experimental plan does not provide details regarding the scope of studies in stanford university mba admissions, Aim 1. Correlates of ADCC to be studied in Aim 1 (“rates of department of psychology mcgill canada, progression and viral loads”) were not described in sufficient detail. How will rates of progression be measured? Will viral load be documented on a continuous scale or will patient viral loads be stratified? An explanation of how the results of Aim 1 experiments will be used to guide the selection of pooled patient sera in Aim 2 would have been informative. A research project spanning the laboratories of two different principal investigators will offer diversity in training and acquired expertise, and davis, enhance the capability of the mcgill university montreal, applicant to develop an independent and productive research career. 5. Institutional Environment Commitment to Training: The resources and davis, facilities at both institutions will provide outstanding environments for department of psychology university montreal canada, training and research. A more detailed plan regarding the coordination of stanford mba admissions criteria, training plans between the sponsor and co-sponsor would be valuable, considering the distance and time difference between the two performance sites.

Training in the Responsible Conduct of Research: Comments on Format (Required): The description of department of psychology mcgill university, 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 university benefits, 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 RCR training. Comments on Duration (Required):

The duration appears to be adequate, although exact contact hours were not provided. Comments on Frequency (Required): The frequency of training could not be discerned from the description of RCR training. Fellowship Applicant: 2. Sponsors, Collaborators, and department of psychology university montreal canada, 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 leslie, reference although she lacks a first author publication. Department Of Psychology University Montreal? The applicant has chosen two superb sponsors with complementary skill sets. In fact, the linda nochlin, applicant brought these two investigators together herself. Both sponsors have excellent training track records and department mcgill university canada, both are actively involved in the HIV arena.

The primary goal of this project is to characterize antibodies that mediate antibody-dependant cellular cytotoxicity (ADCC). The Connors lab at the NIH has developed a novel flow cytometric-based assay to measure granzyme B delivered to university of pennsylvania tuition, an HIV infected cells. Using this novel assay the applicant plans to mcgill, compare ADCC in HIV+ subjects with various rates of disease progression and to at north, define the mcgill university canada, specificity and breadth of antibodies with ADCC activity (Aim 1 and leslie wallick new york, 2). The third Aim to characterize the structure and function of the target-effector synapse will be carried out at Oxford under the guidance of Dr. Sattentau.

This aim will use fixed and live cell laser scanning confocal microscopy and department university canada, TEM to cost state university, examine the samples between NK and other cells with ADCC activity. If the applicant is successful the data from this project will be highly important for HIV vaccine development. The research project however is department of psychology mcgill montreal canada, quite ambitious and no timeline is given. 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. University? Despite the highly ambitious nature of the proposed research project the overall project goals warrant further study and department mcgill university montreal, the applicant herself is university mba admissions, of the highest caliber making this application worthy of funding. The applicant has a very strong research background dating back to high school where she participated in the Gene Search Project at Howard University Hospital. As an undergraduate at UMBC she was a member of the Meyerhoff Scholars Program funded by the HHMI. Department Of Psychology University? The applicant has coauthored 2 papers and is the first author on nochlin new york university, 8 posters and 1 oral presentation. Of Psychology University Canada? The applicant has extremely strong letters of recommendations, one of mba admissions criteria, 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 department of psychology mcgill montreal canada, 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 post-docs Both sponsors have well established complementary HIV research programs that will support the applicants proposed research project. The planned research, if successful, could provide important information about of the role of ADCC in HIV infection.

The project is well outlined and there are sufficient preliminary data to nochlin, support the feasibility of the project. The plan is to mcgill university canada, utilize a novel recently developed (Connors lab) quantitative flow cytometric assay to measure GrB cytotoxicity and determine which Abs are capable of mediating the highest level of ADCC. Using this technique the applicant plans to characterize the potency of stanford criteria, sera from subjects with different rates of university canada, disease progression, characterize the specificity and breadth of university of pennsylvania tuition, antibodies with ADCC activity. Using advance microcopy techniques (fixed and live cell laser scanning confocal microcopy and electron microscopy) the of psychology university montreal, applicant plans to examine the structure and function of the target-effector synapse. This work will be done under the guidance of Dr. Sattentau who is an expert in studying the virologic synapses. This is a highly ambitious grant. It may be difficult for the applicant to stanford university criteria, finish all the proposed work especially the work proposed in Aim 3. The applicant is calling for 300 subjects but no power calculation is shown to support that many subjects. A timeline for the proposed work would be helpful. The applicant does not anticipate any issues nor are any alternative approaches outlined. This maybe a little naive.

The research training plan is well laid out by year. The plan includes research, writing skill (grant writing course), presentation, career development, teaching (both in class room training of of psychology canada, new personnel) and discipline specific learning (i.e. in house courses and university, seminar series, lab meetings). Letters describing each institution’s role in mcgill university, training the applicant were provided. Applicant states that she will interact on daily basis with section head and other senior laboratory member on university of california davis, a daily basis. Students also make formal presentations and attend weekly LIR, meeting, NIAID grand rounds, clinical center Grand Rounds and HIV journal club. The training plan indicates that the applicant will be at the NIH for one year and Oxford for one year and then back to medical school for the last 2 years. Department Of Psychology Mcgill Canada? This raises some concerns regarding the duration of the funding (3 vs. 2 years). 5. Institutional Environment Commitment to Training:

The work will be conducted at the NIH/NIAID and University of university, Oxford. Both institutions are of the department university canada, highest caliber with access to all the required resources. University Of Pennsylvania? Oxford has a program in place for graduate students to take accelerated courses and the NIH Foundation for Advanced Education in the Sciences also has specialized courses that will facility the applicants goal to become an infectious disease investigator. Training in the Responsible Conduct of of psychology mcgill university canada, Research: Comments on Format (Required): On line ethics course at university, the NIH and formal classroom course at 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 Ethics/Integrity in Scientific research. The applicant took another Ethic course upon entering the NIH. Oxford offers a similar course. Comments on Faculty Participation (Required): No comment on faculty participation. Comments on Duration (Required): Comments on department of psychology university canada, Frequency (Required): Online course and annual refresher at the NIH. Additional Comments to Applicant (Optional): Fellowship Applicant: 1.

Sponsors, Collaborators, and Consultants: 1. Research Training Plan: 2. Training Potential: 1. Institutional Environment Commitment to Training: 1. Overall Impact/Merit : This proposal comes from an excellent candidate who is part of the NIH/Oxford/Cambridge Scholars program, carrying out her PhD research under the guidance of two excellent researchers and mentors, Drs.

Connors (NIH) and nochlin, Satentau (Oxford) and will complete her MD studies at department mcgill university montreal, Columbia. The primary hypothesis of this proposal is cost of tuition at north state, 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 mcgill university canada individuals at different stages of athens apartments at ohio university, 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 mcgill university montreal, ADCC synapse. This will involve state-of-art approaches established in wikipedia university, the sponsors’ labs, allowing the applicant an excellent chance to department mcgill montreal canada, perform this research. It is a clear and well-written proposal detailing a strategy to carry out relevant research in an excellent training environment.

THE FOLLOWING RESUME SECTIONS WERE PREPARED BY THE SCIENTIFIC REVIEW OFFICER TO SUMMARIZE THE OUTCOME OF DISCUSSIONS OF THE REVIEW COMMITTEE ON THE FOLLOWING ISSUES: PROTECTION OF HUMAN SUBJECTS (Resume): ACCEPTABLE. INCLUSION OF WOMEN PLAN (Resume): ACCEPTABLE. INCLUSION OF MINORITIES PLAN (Resume): ACCEPTABLE. INCLUSION OF CHILDREN PLAN (Resume): ACCEPTABLE.

COMMITTEE BUDGET RECOMMENDATIONS: The budget was recommended as requested.

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Try to write in department mcgill montreal simple way. Express your views with most appropriate words. Read great writers for inspiration. If you read them enough, their excellent writing style will rub off onto your dazzling blog. Benefits Tuition. YOU ARE what you read (and write!). Department Of Psychology. I watch my action tense and university of pennsylvania wordiness in sentences when I am writing my technical diddley. For example, in a sentence where you say …”you will have to…” I replace it with “…you must…”, or “Click on of psychology university canada the Go button to…” can be replaced with “Click Go to…”. Think of words such as “enables”, instead of “allows you to” or “helps you to”.

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Write often and to completion by following a realistic writing schedule. One that works for me every time is to focus on the positive intention behind my writing. Wikipedia University. What is it that I want to communicate, express, convey? By focusing on department of psychology montreal canada that, by cost at north state university, getting into the state that I’m trying to express, I find that I stop worrying about the words just let them tumble out of their own accord. It’s a great strategy for mcgill university canada, beating writer’s block, or overcoming anxiety about a particular piece of writing, whether that’s composing a formal business letter, writing a piece from the heart, or guest blogging somewhere ‘big’… Use others writer’s sentences and leslie paragraphs as models and then emulate the department montreal syntactic structure with your own content. I’ve learned more about grammar and punctuation that way. Avoid long sentences. Learn the linda university difference between me, myself and I. For example: #8220;Contact Bob or myself if you have any questions.#8221; I hear this very often! When doing a long project, a novel, for instance, shut off your internal editor and just write.

Think of your first draft as a complex outline waiting to canada be expanded upon, and let the words flow. Careful with unnecessary expressions. Of California. “At this point in mcgill montreal time” came along during the Nixon congressional hearings. Too bad it didn’t go out with him. What about new york university, “on a daily basis?” For large documents, I use Word’s Speech feature to have the computer read the article back. This allows me to catch errors I have missed especially missing words or words that ’sort of sound the same’ but are spelled differently (e.g. Front me instead of ‘From me’).

Either read the book “Writing Tools 50 Strategies for Every Writer”, by montreal canada, Roy Peter Clark, or read the Fifty Writing Tools: Quick List on his blog. Then join a writing group, or hire a writing coach. Write the first draft spontaneously. Leslie Wallick New York. Switch off your internal editor until it is time to review your first draft. If you#8217;re writing fiction, it#8217;s a great idea to have a plot. It will coordinate your thoughts and add consistency to mcgill montreal the text. Edit your older articles and pieces. You will notice that great part of it will be crap, and it will allow you to refine your style and avoid mistakes that you used to make. Subscribe to Receive our Articles and Exercises via Email. You will improve your English in only 5 minutes per day, guaranteed!

Subscribers get access to our exercise archives, writing courses, writing jobs and much more! You'll also get three bonus ebooks completely free! Try It Free Now. University Criteria. 93 Responses to #8220;34 Writing Tips That Will Make You a Better Writer#8221; Martin McConnell on August 02, 2017 10:38 pm. Nice list, good information here. I think some of these should be put into mcgill montreal canada focus more in the editing phase though, starting with number 1. A first draft is a creative process, not time to sit an fiddle with tiny details. I move most of my commas 3 times before I do anything (submission or publishing attempt) with a story. Better Writing Tips! on June 23, 2017 4:31 pm. Write as if you’re on deadline and have 500 words to of tuition carolina university make your point.

Then do it again. And again. Department Of Psychology Mcgill Montreal Canada. It is university, funny but, isn#8217;t that where most spam articles come from? 24. Joanna Young. Of Psychology Mcgill University. One that works for me every time is to focus on the positive intention behind my writing.

What is it that I want to communicate, express, convey? I wish more people would commit to just that. #8220;Start the nochlin new york university article with a short sentence, not more than 8 words.#8221; *article starts with thirteen words* Copyright 2017 Daily Writing Tips . All Right Reserved.

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SAT / ACT Prep Online Guides and Tips. The dreaded DBQ, or “document-based question,” is an essay question type on the AP History exams (AP US History, AP European History, and of psychology mcgill montreal canada AP World History). For the DBQ essay, you will be asked to analyze some historical issue or trend with the aid of the of pennsylvania, provided sources, or documents, as evidence. The DBQ is an unfamiliar type of in-class essay for many students, but it does not need to be a source of dread or panic. In this guide I'll go over the DBQ's purpose and format, what the documents are and how to department of psychology mcgill use them, how this type of essay is scored, and how to prepare.

I'll tell you everything you need to rock this unique type of essay! Note: The rubric, guidelines, and skills tested for all of the History APs are identical; only the athens apartments university, historical source material is different. As a veteran of the DBQ, I'm here to answer all your questions. Why do the AP History exams even have a document-based question? What will it look like on the exam? What are these documents, anyways? Let's dive right in. This baby is of psychology university montreal canada too young to be diving into stanford university mba admissions criteria the DBQ!

The point of the document-based question is not to torment you but actually to put you in the historian’s shoes as an department mcgill canada interpreter of historical material. Cool, right? The DBQ is testing your ability to: create a strong thesis and support that thesis with the aid of the documents provided analyze sources for characteristics such as author’s point of cost at north carolina state university view, the author's purpose, the department of psychology, audience, and context make connections between the documents bring in outside knowledge to strengthen the argument. This may sound like a tall order, but you probably already use all these skills all the time. Suppose your friend asks for your help in deciding whether to buy a particular new brand of athens apartments at ohio soccer ball. You have used the soccer ball, so you have personal knowledge about it, but he doesn’t just want your opinion—he wants evidence! (Your friend takes buying soccer balls very seriously).

So first, you collect information (your “documents”). These could include: online reviews of the soccer ball your brother’s opinion the price at the store the cost of other soccer balls ads for the soccer ball. Next, you'll analyze these documents to make a decision about whether the department mcgill university montreal, ball is cost at north state a good purchase for your friend or not. For that, you might: Assess bias (also known as the author’s point of view): Maybe the soccer ball ad isn’t the most objective measure of the canada, ball’s quality. Maybe your brother hates soccer. Consider the author’s audience: Maybe that review of the soccer ball was written for professional soccer players, and you want to university know how it is for casual players! Think about the context of your friend's decision: What time of year is it? If it’s right around Christmas, maybe your friend’s mom will get it for him as a present.

What you already know about soccer is part of the context as well--you know your friend won’t want a ball that’s too bouncy, for example. Buying the right soccer ball might have higher stakes than the of psychology mcgill canada, AP exam. If you were going to go back and write an essay for your friend about this after you've reviewed your documents, your thesis might be something like one of these examples: “This soccer ball is a good purchase for my friend because it has all the elements of a good soccer ball at criteria a great price point.” “This soccer is not a good purchase for my friend right now because even though it looks amazing, I know my friend’s birthday is in a week and his sister might buy it for him.” Then you would use the “documents” and of psychology university canada your outside knowledge (for example, your experience with the soccer ball and your knowledge about soccer) to new york university support that claim. That's a document-based question! In fact, I would assert that the DBQ is the easiest essay to score highly on mcgill montreal canada, in the AP History exams. As overwhelming as it might be now to think about all of that information getting thrown at you at once, think of it this way: Instead of relying primarily on your knowledge, the DBQ gives you a bunch of criteria sources to department of psychology use in your analysis. This means you don’t have to be worried you’ll waste five minutes racking your brain trying to remember the of california davis, name of that guy who did that thing.

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You won't be forced to move on from one essay to the other, so be sure to budget your time carefully. You are not required to department montreal use the entire reading/planning period. You can begin writing whenever you wish. However, be sure you plan carefully because the writing will go much faster if you have a good outline. That covers the leslie university, general format, but no doubt you want to hear more about these mysterious documents. Stay tuned! What's the Deal With These Documents?

You will receive up to seven sources. Department Mcgill Montreal Canada. These could be primary or secondary, and they could take almost any form: l etters, newspaper articles, maps, pictures, cartoons, charts, and so on. You will need to of tuition at north carolina state university use all or all but one of the department of psychology, documents in your essay. You should go further in-depth on cost of tuition at north carolina state, at least four of the documents. (See the of psychology university, rubric breakdown section below for more details). For US History, no DBQ will focus exclusively on the time period prior to 1607 or after 1980, although they may focus on leslie new york, a broader time period that includes one of mcgill montreal those time periods. Don't worry, they won't be original copies. Now that we've discussed the purpose, format, and document protocol of the DBQ, we need to discuss scoring. How much is the DBQ worth on your exam? And how do those pesky AP graders even score it?

How Much Is the Document-Based Question Worth? The DBQ is 25% of your total grade. The entire second section of exam is 50% of your grade, and apartments at ohio there are two equally weighted essays. The rubric the graders use is freely available to you on the College Board website. Don't worry if these look like gibberish to you. I'll break it down briefly here, and go even more in-depth on my article about how to prepare for and write a DBQ. There are four categories in this rubric: thesis, analysis of the document, using outside evidence, and synthesis.

You can score up to seven points. One point for department mcgill montreal having a clear, historically plausible thesis that is athens located in the introduction or conclusion. You can get another point here for department of psychology university canada having a particularly good thesis that presents a nuanced relationship between historical factors, and doing a good job supporting that thesis in your essay. One point for using 6-7 of the university mba admissions criteria, documents in your essay. Easy-peasy. One point for of psychology mcgill doing further analysis on four of the documents. Leslie Wallick New York University. This further analysis could be on any of the following points: author’s point of view author’s purpose historical context audience. Just be sure to tie any further analysis back to your main argument! One point is just for context - if you can locate the issue within its broader historical situation.

You do need to university montreal canada write several sentences about it but the leslie wallick university, contextual information can be very general. Department Of Psychology University. One point is for being able to name an athens apartments at ohio university additional specific example relevant to university your argument that is wikipedia not mentioned in the documents. Of Psychology University Canada. Don't stress if you freeze up and of pennsylvania benefits can't remember one on test day. This is department of psychology university canada only one point and it will not prevent you from getting a 5 on the exam. All you need to do for synthesis is relate your argument about this specific time period to a different time period, geographical area, historical movement, etc. Athens University. It is probably easiest to do this in the conclusion of the essay. Still with me?

Just remember: the most important thing is department of psychology university having a strong thesis that is supported by leslie wallick new york, the information in the documents and department of psychology university montreal whatever other related information you have around in stanford mba admissions your brain. If you are an auditory learner, I recommend the following video, which breaks down all the department of psychology canada, components you need to get a seven . If this seems like a lot to take in, don't worry. You don’t have to get a perfect score on the DBQ to get a five on the AP. Somewhere in the 5-6 range can definitely get you there. To get a 3 on the exam (which still gives you course credit at a lot of colleges), you only need a 3 on university, the DBQ. Department. (See page eight of this document.) Additionally, overall historical accuracy is important but not 100% necessary for every tiny detail of the essay. Anything that is in the documents should be correct, but when you start to bring in outside sources for your DBQ essay on unionization and working conditions and you can’t remember if the Triangle Shirtwaist Factory Fire was in 1911 or 1912, just pick one and don’t sweat it. If minor details are incorrect and don’t detract from the mba admissions criteria, overall meaning of the essay, you won’t lose points. Now that you understand the purpose, format, and rubric for department of psychology montreal document-based questions, I'll give you some tips on how to get the nochlin new york university, score you're aiming for.

Two things will help you crush the DBQ: prepping beforehand, and hitting all the right notes on test day! Rock the DBQ like Jimi rocked the 1960s. Try out the department of psychology mcgill university montreal, practice DBQs available online at the College Board website: look here for AP US History (and here for a complete APUSH practice test), here for AP European History, and here for AP World History. University. You don’t necessarily have to write an entire essay every time you practice—it’s also helpful to read the question and texts and department canada then create outlines with a thesis. Ask a trusted teacher or advisor to look over your practice drafts and/or outlines with the rubric and advise what you might be missing. Make sure you know general historical trends/periods so you can get that point for context. You can find more prep tips in my article on of pennsylvania benefits, how to write a DBQ.

Read the department mcgill university montreal, question carefully . Make sure you know what is being asked before you start trying to answer. While you read the davis, documents, take notes on what they mean, who is writing, etc. Come up with your thesis before you start writing, or your essay will be a sad, directionless mess, like a boat with no rudder, lost at sea forever. If you aren’t sure of your thesis yet, brainstorm in your notes — not while you are writing. Once you have a thesis, stay on topic. If you’re writing about how Smaug wrecked the Forbidden Mountain, don’t start talking about how amazing and clever Bilbo is, even if it’s true. Make sure you use all the documents —doing so gets you easy points.

However, don’t simply regurgitate sources with no analysis. If you find yourself doing a lot of “Source A says blah, and of psychology university canada Source B says blah, and Source C says blah. ” make sure you are using the documents to make a point , and athens apartments not letting the department mcgill montreal canada, documents use you. A great way to analyze the university, documents is to make connections between them! Who agrees? Who disagrees? Why? Don’t forget to provide context, one outside example, and a connection to another period/area/historical theme if you can! That’s three points right there.

And there you have it! You are ready to department of psychology montreal canada start prepping for success. Abraham Lincoln believes in you! I know I just threw a lot of information at of pennsylvania tuition you. So here are some key takeaway points: The document-based question is a way for the AP to test your skills as a historian! Don’t panic! It doesn’t have to be overwhelming, even though you are getting tons of information thrown at you in a short time. The DBQ is department of psychology montreal canada based on skills that you can learn and practice : writing a strong thesis, using given evidence to support an athens apartments at ohio university argument, making connections between different documents and pieces of evidence, placing specific information in a broader context, analyzing an author’s intent, bias, audience, etc. Need more study resources for AP World History ? See our Best AP World History Study Guide or get more practice tests from our complete list.

Need more resources for AP US History ? Try this article on mcgill montreal canada, the best notes to use for studying from one of our experts. Also check out wikipedia davis, her review of the best AP US History textbooks! Or just looking for general information about your upcoming APs ? See here for department instructions on how to register for AP exams, complete 2016 test dates, and university davis information on how much AP tests cost (and how to department of psychology montreal canada get AP financial aid). Want to improve your SAT score by 160 points or your ACT score by 4 points? We've written a guide for each test about the top 5 strategies you must be using to have a shot at improving your score. Download it for free now: Have friends who also need help with test prep? Share this article! Ellen has extensive education mentorship experience and is deeply committed to university of pennsylvania tuition helping students succeed in of psychology mcgill montreal all areas of life. Stanford University Criteria. She received a BA from Harvard in Folklore and Mythology and is currently pursuing graduate studies at Columbia University.

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