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Physics gcse coursework help

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art essay structure Tristanne Connolly, Department of English, St. Jerome's University. You can skip ahead to coursework help advice on: Essays usually begin with one introductory paragraph. The first section of solve with, this paragraph eases the reader in. You could be writing about anything at this point, so use your introduction to let readers know what you are writing about, and physics gcse help, get them interested. Possible ways to do this are: Find a quotation that reflects your ideas, or sums up what you want to say in an interesting, snappy way.

You have a ready source for derek bruening, quotations in the piece of literature you're writing about. If you take your quote from another source, make it clear to the reader where it comes from: not just the gcse name of who said it, but brief background, such as who that person is, and in what context it was said. Also relate it clearly to the topic (and text) at hand. Give an example. Is there an especially interesting instance of what you are writing about? Use it to pull the reader in.

Remember, though, that in the body of your essay you will be using examples to prove your point; this is a different kind of example, used only to introduce your point and intrigue your reader. A Problem With Ati Graphics Driver! Start with the general and move to the specific--but not too general. Coursework Help! Avoid the society today and most people kind of generalization because they are often untrue and nyu creative graduate school, always uninteresting. Physics Gcse Coursework! (William Blake once wrote, To Generalize is to be an Idiot. Why? Because there is always an exception, and because the details or minute particulars you use to derek bruening thesis prove your general idea are where the physics gcse help truth resides.) Give some background. What does the with ati graphics reader need to know about your topic, not only to get interested, but as a basis for what you intend to say? Explain an coursework, issue. Why is your topic important? What is at stake? Offer a definition. Solve A Problem With Driver! Beware, just pulling a definition out of the dictionary can seem quite boring.

If you do, comment on it, put a twist on it, contest it; or, come up with your own definition for physics gcse help, the purposes of install thesis, your paper. Note that handbooks to literature can offer fruitful and even contestable definitions of coursework, literary terms and devices. Ask a question. This gets readers involved, inviting them to answer your question mentally. But keep control of the situation in case they answer in a way that doesn't serve your point.

When you use rhetorical questions in your essays, always make sure to answer them. Make a comparison. The thing you are writing about, what is it like? Does your paper use comparisons that you can introduce right away? Is there a metaphor you can use to shed light on nyu creative, what you are saying? Tell a little story or anecdote related to your topic. In very formal essays, this is the physics only place where you might be able to get personal. Make sure your introductory story is not too long. If necessary, give it its own short paragraph and let the solve a problem ati graphics next paragraph do the physics job of the introduction. Present a mystery. Make what you are writing about sound interesting and complicated by addressing its contradictions, or its fascinating unknowns.

However, simply saying we will never know makes the reader feel as though you have no new insight to provide: go further and make some kind of derek, suggestion, even if it is tentative. Next, give a few transitional sentences to move from your hook or attention-getter to gcse your thesis. A good thesis statement or main idea is the key to a good essay. It is usually one sentence but can be two if necessary, and it is traditionally placed at the very end of your introduction (this is the spot where teachers, grading stacks of papers, tend to look for it). Install Thesis! It is the main thing you are trying to say or argue in your essay, and all of your body paragraphs will go to prove, support and elaborate on it. It is the pin that holds your essay together.

A topic is what your essay is physics coursework, about, while a thesis is your stand, your particular, focused statement or argument on that topic, the insight that all of your points come together to show. Here are some ways to & Editing improve thesis statements: Make sure your thesis makes a claim . For instance, if you say there are many similarities and differences or this essay will address the characteristics of. Physics Gcse Coursework Help! , you could get more specific. What similarities and differences? What characteristics? What do they have in common? And what does it all mean? Are there any interesting contradictions involved, e.g., are there opposite write my report survey characteristics working together, or characteristics that could have the opposite effect? Make sure your thesis is not obviously true: a statement of physics gcse coursework help, fact or a clich.

Instead, can you put a new twist on an old idea, or contest received wisdom? You are not really proving anything if you are restating common knowledge. With Driver! Make sure your thesis can be proven within the constraints of the assignment. Know what kind of evidence to use for a particular assignment, and make sure your thesis fits. Coursework! For instance, when you are writing a literary essay, you must make sure your main point focuses on the text itself, and can be supported by textual evidence, rather than some other kind, such as personal experience, or statistics. & Editing! These might be helpful for physics coursework help, some small points, but if they're necessary to the main idea, then it's no longer a literary essay. When your essay assignment requires research, you must make sure your point can be proven reliably using sources you are able to find.

Make sure your thesis is write my report on my survey, not based only on help, opinion. Particularly, judgments such as good or bad, true or false, are hard to prove for this reason. Pros Wearing School Essay! Could you say something about the significance of the topic instead? Or examine why you think something is true or false, good or bad? Iif you are automatically stating your opinion without considering it, you are not thinking very deeply and may be in gcse help the realm of clich.

Dealing with a text, think about how the writer seems to feel about the pros school uniforms essay topic, and be aware that she or he may not agree with you (or even the speakers in the text!). In all cases, question your assumptions. Coursework Help! Imagine counterarguments and other views. Find out the reasons for your opinion, and that may lead you to a point you can explain and prove. A Problem With Driver! Additionally, it will help you communicate with your reader, who may have a different point of view. Make sure your thesis is focused: not too broad. Is your claim too general to be convincingly proven with a few examples? Try to define it: you do not need to account for everyone or everything. Can you develop your point and prove it within the page limit? Sometimes it is better to say more about less.

You can pick one of the things you intended to help address, or concentrate on wearing, one particular aspect of the topic. Gcse Help! You will notice that most of these problems with main ideas can be solved by getting more specific and more analytical . Ask the questions, What exactly? and What does it all mean? or What does it all teach us about ___? Complications can actually help you. Pros Cons Wearing! If you come up against difficulties and contradictions in your thinking, don't sweep them under the carpet. Think about gcse coursework, how you can turn them around to derek bruening thesis prove your point anyway, or think how you can use them to physics coursework define your idea more precisely. The thesis must not only state a claim worth proving; it must also give the reader an install thesis, idea of how you intend to develop your main idea. For instance, if you have three sub-points to your main idea, you can list them in brief in the same order you will discuss them in your body paragraphs. Also, make sure that your main idea effectively ties together all three (or however many) of your sub-topics. What do they have in common? What makes them different?

The thesis is like a preview of your essay. This means that it helps a lot to physics gcse help have an idea of what you are going to say before you begin to write a first draft -- and that if your idea changes as you write and experiment, you should go back and change the a problem thesis to physics gcse fit. Do not save your main point for your conclusion: essays are not suspense stories or poker games. Solve Driver! Lay your cards on the table in the introduction. Physics Coursework Help! However, remember that in your body paragraphs you will prove and derek thesis, expand on your main idea: the introduction shows exactly where you are going, and in the body paragraphs you go there. Physics Coursework! You can have as many body paragraphs as you wish. However many sub-topics you have to & Editing prove your thesis, that is how many body paragraphs you will have. You can place them in any order, so long as it makes sense.

For instance, you can: *place the strongest argument last. *move in chronological order. *move from causes to effects. *alternate: if you are writing about more than one thing, move back and gcse coursework help, forth between them. Uniforms Essay! *chunk: if you are writing about more than one thing, write all about one then all about the physics help other. Write On My Survey! Every body paragraph must have a topic sentence which is like a mini-thesis, and physics, which is usually placed at install thesis or near the beginning of the paragraph (indicating what you are going to gcse coursework prove), but can also come at the end (indicating what you have just proven). The topic sentence expresses the main point this paragraph is out to demonstrate. Keeping aware of your topic sentences can help you make sure your paragraphs are well-developed . Give as much proof and explanation as you can for Proofreading, your sub-point in each paragraph. Go into detail. Make sure in every paragraph you: *offer some kind of evidence . For a textual or literary essay, your evidence will be specific references to gcse coursework help the text along with logical argument and explanation of your interpretation. In a research essay, you will also include references to derek thesis respectable scholarly work on the topic, not so much as evidence but as other voices in physics gcse help the debate over my report on my survey, the text--you're having a written conversation with fellow scholars. *offer full explanation of how and why your evidence proves your point , and how and why that point relates back to your thesis. If any of your paragraphs are lacking either of these things, something is wrong with them and physics, they must be fixed. E.g., a paragraph that is all evidence or summary with no explanation indicates no brain work on your part: you need to analyze your evidence and explain what it means, particularly in pros school relation to coursework your main idea.

Conversely, a paragraph that is all assertions gives the reader the impression you are talking through your hat. Essay readers will not take your word for it. If you are arguing something reasonable, you should be able to prove it, and if you don't it will look like you can't. For every assertion you make, give proof and explanation. Topic sentences can also help you make sure your paragraphs are all unified . Each paragraph should be about only one thing . If there is any sentence in a paragraph which is not on & Editing, topic, it should either be moved to the paragraph where it belongs, or thrown out. Coursework! If nothing in the paragraph can be clearly related to nyu creative writing graduate school your essay's main idea, the whole paragraph has to go. Your body paragraphs must all work to physics coursework help prove your thesis: this makes your essay coherent . To assure your reader that your essay is install thesis, coherent or hangs together, you need to have smooth transitions between paragraphs. A formulaic way to move from one paragraph to the next is to say something like, Another example. Physics Gcse! or The third point is. , but this is very mechanical and ati graphics driver, so doesn't have the finesse of an physics gcse coursework help, A paper! Using such formulae is handy for a first draft, but as you improve your paper, try to replace mechanical transitions with more interesting ones. Think about the ideas you are trying to express: what do they have in common?

What is the difference between the last idea and this one? You can use the similarities and differences to compose interesting transition sentences which help you show why you decided to organize your paper the way you did, and also give more significance to my report on my survey your points. Handy comparison and coursework, contrast words can assist you here: (of course you will fill in the details!) Although/While this last idea is with ati graphics, like this, this next idea is like that; This last idea is like this, and this new idea is also/similarly like this with these important differences or further details. You can also use time sequence (e.g. Next/Meanwhile ), or cause and effect (e.g. Consequently/If. then ). The conclusion of an essay wraps things up. Physics Help! It reiterates the main idea in different words, and looks back over how the thesis was proven. This is not just repetition: it gives you an opportunity to show how you have developed your idea, to indicate what the reader has learned by reading your essay. As well as summing up , the conclusion should leave the reader satisfied that the time it took to read the essay was well spent.

So, remember Miles Davis and answer the question, So What? Why is all this important? What are the implications of what you have argued? What does it mean in the big world? As in Proofreading & Editing your introduction, though, be careful not to over-generalize , making a claim that your essay is more important than it is or has proven more than it has. No new information should be offered in the conclusion; only the gcse ideas already presented, seen in a new light. Some ways to put a sting in on my survey the tail of your essay: Quotation. Find one that reflects or sums up your point in a clever and physics coursework help, memorable way. Figurative language. Writing! Metaphors and images can leave a striking idea or picture in the reader's mind, and you can use them to elaborate on your insight.

Especially if you use one in the introduction, bring it up again and gcse coursework, see how you can use it a bit differently. Example or anecdote. A brief story or example can make the implications of your point more vivid, and place your ideas in a wider context. Predictions or speculations. What follows from what you have argued? Make sure you don't speculate too far; stick to what seems plausible from pros uniforms essay, what you said previously. And a finishing touch: a great title. A good title is not too vague, yet not too long either. Physics Help! A good way to & Editing think about it is, if a person were trying to find articles on your topic in a database, would your title have enough of the physics gcse coursework right keywords to pop up? Be sure to install thesis mention the text and/or author you're writing about, and include words which reveal something about the main drift of coursework help, your argument.

These are the mechanics of an nyu creative writing, appropriate title; of help, course, you also want it to be interesting. A unique or clever turn of phrase can do this for Proofreading, you. You can also take a short phrase from the physics coursework help text which you think particularly relates to what you have to say, and place it before your main title, with a colon to connect them. Here's an example. Wild Ecstasies and Sober Pleasure: The Relationship between William and derek thesis, Dorothy Wordsworth in physics Lines Written a Few Miles above Tintern Abbey

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

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

Performance sites are in New York, Maryland, and the United Kingdom.] Research Related Other Project Information. [Our Web version of this sample application can't reproduce the layout of the actual PDF forms. Here are the key fields from that form and the applicant's responses.] Understanding the basis of an derek thesis immune response that controls infection or provides sterilizing immunity remains a major goal in the search for effective vaccines or immunotherapies for HIV. Physics Gcse? 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 school 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. Physics Gcse Coursework? 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 wearing uniforms 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 gcse help characteristics of the best responses achieved by natural infection. Solve A Problem With Ati Graphics? 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 physics gcse help 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 install thesis the characteristics of Abs that mediate ADCC that are likely important goals in the design of HIV vaccines or immunotherapies. Hypothesis: Antibody-dependent cellular cytotoxicity (ADCC) is gcse coursework help a function that has been shown to mediate protection from lentiviral infection. Writing School? We hypothesize that variations in ADCC activity of sera are dictated by the amount, specificity, and subclass of physics gcse HIV-specific antibodies. Aim 1 : Characterize the potency of sera of HIV-infected individuals in ADCC.

Aim 2 : Characterize the specificity and breadth of install thesis antibodies with ADCC activity. Aim 3 : Characterize the structure and function of the target-effector synapse using both fixed and gcse coursework help 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 write HIV could provide important insights for physics, 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. Gallo RC, Salahuddin SZ, Popovic M. Frequent detection and isolation of wearing school uniforms cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science.

1984; 224: 500-3. Barre-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, et al. Isolation of physics coursework help a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Install Thesis? 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. Physics? Fc receptor but not complement binding is important in antibody protection against HIV. Nature. Write On My Survey? 2007; 449(7158): 101-4. www.hivresearh.org.

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

J Immunol. 1977; 118(3): 729-35. Forthal DN, Landucci G. In vitro reduction of Proofreading virus infectivity by antibody-dependent cellmediated immunity. Journal of help immunological methods. 1998; 220(1-2): 129-38. Stratov I, Chung A, Kent SJ. Robust NK cell-mediated human immunodeficiency virus (HIV)-specific antibody-dependent responses in HIV-infected subjects. Thesis? 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 help antibody-dependent cell-mediated cytotoxicity. Journal of immunological methods. 2006; 308(1-2): 53-67. Derek Thesis? Migueles SA, Osborne CM, Royce C, Compton AA, Joshi RP, Weeks KA, et al. Lytic granule loading of CD8+ T cells is required for HIV-infected cell elimination associated with immune control. Immunity. 2008; 29(6): 1009-21.

Vago L, Perna SK, Zanussi M, Mazzi B, Barlassina C, Stanghellini MT, et al. Loss of mismatched HLA in physics leukemia after stem-cell transplantation. Write Survey? N Engl J Med. 2009; 361(5): 478- 88. Ziegner U, Campbell D, Weinhold K, Frank I, Rutstein R, Starr SE. Deficient antibodydependent cellular cytotoxicity against human immunodeficiency virus (HIV)-expressing target cells in perinatal HIV infection. Clin Diagn Lab Immunol. 1999; 6(5): 718-24. Brunetta E, Fogli M, Varchetta S, Bozzo L, Hudspeth KL, Marcenaro E, et al.

The decreased expression of Siglec-7 represents an early marker of dysfunctional natural killer cell subsets associated with high levels of HIV-1 viremia. Blood. 2009. Physics Coursework Help? Ljunggren HG, Ohlen C, Hoglund P, Yamasaki T, Klein G, Karre K. Afferent and efferent cellular interactions in natural resistance directed against & Editing, MHC class I deficient tumor grafts. Physics Gcse Coursework Help? J Immunol.

1988; 140(2): 671-8. De Maria A, Ferraris A, Guastella M, Pilia S, Cantoni C, Polero L, et al. Expression of HLA class I-specific inhibitory natural killer cell receptors in HIV-specific cytolytic T lymphocytes: impairment of specific cytolytic functions. Proceedings of the National Academy of Sciences of the United States of America. 1997; 94(19): 10285-8.

Ahmad R, Sindhu ST, Toma E, Morisset R, Vincelette J, Menezes J, et al. Evidence for a correlation between antibody-dependent cellular cytotoxicity-mediating anti-HIV-1 antibodies and pros wearing prognostic predictors of HIV infection. Gcse Coursework Help? J Clin Immunol. 2001; 21(3): 227-33. Install Thesis? Lambotte O, Ferrari G, Moog C, Yates NL, Liao HX, Parks RJ, et al. Heterogeneous neutralizing antibody and antibody-dependent cell cytotoxicity responses in HIV-1 elite controllers. AIDS. 2009; 23(8): 897-906. Dalgleish A, Sinclair A, Steel M, Beatson D, Ludlam C, Habeshaw J. Failure of ADCC to predict HIV-associated disease progression or outcome in a haemophiliac cohort. Clin Exp Immunol. 1990; 81(1): 5-10.

Koup RA, Sullivan JL, Levine PH, Brewster F, Mahr A, Mazzara G, et al. Gcse Coursework? Antigenic specificity of cons antibody-dependent cell-mediated cytotoxicity directed against human immunodeficiency virus in antibody-positive sera. J Virol. 1989; 63(2): 584-90. Gcse Coursework? Doria-Rose NA, Connors M. Antibody-secreting B cells in install thesis HIV infection. Curr Opin HIV AIDS. 2009; 4(5): 426-30. Burke B, Barnett SW.

Broadening our view of protective antibody responses against HIV. Current HIV research. Physics Gcse Help? 2007; 5(6): 625-41. Sattentau Q. Solve Ati Graphics Driver? 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. Help? 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. Nyu Creative Graduate? HIV-1 cell to cell transfer across an physics gcse coursework help Env-induced, actin-dependent synapse.

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

Intellectual Support : My mentors Mark Connors and Quentin Sattentau are leading experts in their field and have mentored numerous people that have gone on to successful careers in gcse coursework help science. Install Thesis? This dual mentorship will teach me to aggressively approach science from two distinctive perspectives in my graduate career, something most PhD scientist don’t experience until their first post-doctoral experience. While at NIH I will have received extensive support of staff from gcse coursework help Richard Siegel, Director of the NIH MD/PhD partnership program and Michael Lenardo, Director the NIH/Oxford/Cambridge Scholars Program. While at Oxford I will have the guidance of install thesis 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 physics help FAES at NIH I have access to courses to improve lab specific skills and foundation knowledge. I have already participated a Vaccine Development course. At Oxford I will take seminars at the Centre for Excellence in Teaching and write my report on my survey Learning for training in teaching skills. I will also take courses pertinent to my research offered at the Dunn School of Pathology. Both the NIH and Oxford have libraries and IT staff that can aid me in scholarly research. Physical Resources : Both labs have sufficient funding to provided me any reagent/equipement need for gcse help, the proposed research. Lab Space – I am provided with a desk and solve with personal desktop computer.

Bench space is shared within the gcse coursework help lab. Safety – In order to write ensure our safety from hazardous blood samples we work under laminar flow hoods in a P2 facility with P3 practices. Samples – We receive blood samples from patients enrolled within our protocol. We also have access to the NIH blood blank for normal human blood samples. As provided by coursework Quentin Sattentau: “Oxford University is held in high international regard for its strong teaching and research background and its unique and personal teaching style. Within the University the Department of Pathology has an excellent reputation for graduate teaching, and has achieved 100% success in & Editing DPhil graduation within 4 years for physics gcse coursework help, the past 3 years.

The Department has a strong graduate support structure, in which each student has a principal supervisor, the possibility of a cosupervisor, a departmental advisor, and writing school a college advisor. The supervisor(s) will generally meet with the student multiple times a term, and coursework each of the non-supervisory mentors will meet with the nyu creative school candidate approximately once a term and will file reports on gcse coursework help 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 cons essay term time, and a regular series of internal seminars from leading and more junior University and physics Departmental investigators and & Editing students. Adjoa will attend and participate in the weekly lab journal club, in physics gcse coursework help which scientific papers are taken apart critically by members of the write my report group, and gcse coursework a weekly laboratory meeting in which each lab member presents their ongoing research. Adjoa will also be encouraged to & Editing chat to gcse 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 install thesis writing. Adjoa will have her own writing up space close to her work bench, equipped with a portable computer and if required, an external screen. Physics Gcse Help? Adjoa will have full access to all core facilities, including the imaging suite with multiple light microscopes, a flow cytometry and write my report on my survey sorting suite, an electron microscopy facility with full technical and physics gcse help scientific support. Wearing School? We also have strong connections with the biochemistry and chemistry departments and the Weatherall Institute of Molecular Medicine at the John Radcliffe Hospital for obtaining clinical samples and expertise.”

BD FACSAria IIu. BD Pathways 855. VICTOR Light luminescence plate reader. AutoMACS Pro Separator. AutoMACS Classic Separator. Containment II/III Laboratory with 4 tissue culture hoods. Tissue culture. Coursework Help? 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 install thesis 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 molecular biology carried out under containment levels –I, -II and gcse coursework help –III. Light microscopy. The department has 5 confocal microscopes of varying sophistication and resolution, two of which are set up for cons wearing uniforms essay, live cell immunofluorescence work. The department has three recently acquired high-speed CCD cameras and associated microscopes for live cell immunofluorescence analysis.

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

[Our Web version of this sample application can't reproduce the layout of the actual PDF forms. See below for the biographical sketch attachments.] My interest in studying infectious diseases stems from the 2001 anthrax scare in the Washington D.C. area. Write Survey? I already had a strong interest in science but through my participation in the Gene Search Science Project at Catholic University the following summer I came to understand how medical research impacts treatment for routine illnesses and also plays a role in national defense. Since middle school I have been preparing for a career in science. At Eleanor Roosevelt High School I was enrolled in the rigorous Science and Technology Program during which time in physics gcse participated in the Gene Search Project and researched biochemical pathways that influence sickle cell anemia with Dr. William Winters at Howard University Hospital. This experience taught me how research and medicine are intertwined and inspired me to become a physicianscientist. At UMBC I was a member of the Meyerhoff Scholars Program and & Editing an HHMI Undergraduate Research Scholar where numerous lab experiences, seminars, rigorous classes, and multiple opportunities for scientific presentations prepared me for a career as a scientist.

My lab skills and understanding of a research career increased exponentially during my four years in coursework help Michael Summers’ lab. Not only did I learn about bruening thesis, protein purification, gel electrophoresis, NMR, and ITC while studying MuLV RNA packaging, but more importantly of the time and physics gcse discipline necessary for excellent research and the internal drive that keeps one focused. Working with Dr. Pros Cons School Essay? Nikola Pavletich I learned the value of immediately organizing my data so that others could analyze my results quickly. In the lab of physics coursework Tom Cech I had the responsibility of designing a new protocol to study telomerase assembly, a skill that has enabled me to design a novel assay to investigate AIDS specific questions in my graduate studies. The medical education I’ve received at nyu creative writing graduate, Columbia has given me a unique perspective with which I approach scientific questions. Physics Gcse? Under the tutelage of Mark Connors and Quentin Sattentau, leaders in install thesis their fields on nonprogressive HIV infection and viral transmission, my understanding of physics help infectious disease and my capacity to nyu creative writing graduate school pursue further research in these fields will be greatly enhanced. In addition, the physics gcse coursework help 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 nyu creative graduate, 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 physics gcse help RNA to install thesis 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.

J Mol Biol. 404(5), 751-772. Smalls-Mantey A, Winter W. 2003. Coursework Help? Biosynthesis of 2,3-diphosphoglycerate in Erythrocytes. Poster presentation at Proofreading & Editing, 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 help Moloney Murine Leukemia Virus RNA Packaging Signal.

Poster presented at 2004 Annual Biomedical Research Conference for solve with ati graphics driver, Minority Students, November 2004. Smalls-Mantey A, Min J, Pavletich N. Physics Gcse? 2005. Structural and Biochemical Studies of the Yeast Rad4-Rad23 Complex Bound to DNA. Poster presented at Tri-Institutional Gateways to the Laboratory Program Symposium and 2005 Leadership Alliance. August 2005. Write? Smalls-Mantey A, Miyazaki Y, Summers MF. Gcse Coursework? 2007.

Dimerization of Moloney Murine Leukemia Virus Nucleocapsid Protein Binding Sites Facilitates Binding. Poster presented at 2007 UMBC Undergraduate Research and pros cons Creative Achievement Day. April 2007. Smalls-Mantey A, Klein R, Doria-Rose N, Laub L, Rood J, Migueles S, Sattenatu. Physics Coursework Help? 2010.

HIV-Specific Antibodies Mediate Rapid Antibody-Dependent Cellular Cytotoxicity Against Primary HIV-Infected CD4+ T Cells. Poster presented at 2010 Keystone HIV Vaccines (X5) Meeting. March 2010. Smalls-Mantey A, Klein R, Doria-Rose N, Laub L, Rood J, Migueles S, Sattenatu. 2010. HIV-Specific Antibodies Mediate Rapid Antibody-Dependent Cellular Cytotoxicity Against Primary HIV-Infected CD4+ T Cells. Poster presented at 2010 Oxford Pathology Department Graduate Student Symposium. June 2010. Nyu Creative? 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 coursework, 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. November 2010. [Outside research support redacted from cons essay sample.] A. Personal Statement Regarding Project. Currently HIV-specific ADCC is gcse coursework considered one of the very top priorities in the field of HIV-specific immunity.

Our laboratory has assembled the best techniques and reagents in the field to a problem ati graphics driver carry out this project. We have extensive experience in HIV-specific antibodies and cytotoxicity. In addition we have a long track record of training students to prepare them for a carreer in biomedical research. 1985 - 1986 Intern in Pediatrics, The Boston Floating Hospital, New England Medical Center, Boston, Massachusetts 1986 - 1988 Resident in Pediatrics, The Boston Floating Hospital, New England Medical Center, Boston, Massachusetts 1988 – 1989 Chief Resident in Pediatrics, The Boston Floating Hospital, New England Medical Center, Boston, Massachusetts July 1989 - October 1989 Medical Staff Fellow, Respiratory Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD October 1989 - June 1993 U.S. Public Health Service, Research Associate (C.O.), Respiratory Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and gcse coursework 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 pros school uniforms Infectious Diseases, National Institutes of Health, Bethesda, MD January 1994 - June 1994 Clinical Fellow in Infectious Diseases, The Childrens Hospital of Philadelphia, Philadelphia, PA. June 1994 - December 2004 U.S. Gcse Coursework Help? Public Health Service, Medical Officer, National Institute of solve 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 coursework Pennsylvania 2009 - present HIV Enterprise Host Genetics and HIV Diversity Working Group 2010 - present Editorial Board, Journal of Virology. C. Peer-Reviewed Publications. Migueles SA, Sabbaghian MS, Shupert WL, Bettinotti MP, Marincola FM, Schwartz D, Sullivan J, and Connors M. HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV infected long term nonprogressors. PNAS 2000; 97(6): 2709-2714. Pros Cons Uniforms? 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 gcse coursework Connors M. HIV-specific CD8+ T cell proliferation is coupled to perforin expression and write my report survey is maintained in nonprogressors. Nature Immunol 2002; 3(11); 1061-1068.

Migueles SA, Laborico AC, Imamichi H, Shupert WL, Royce C, McLaughlin M, Ehler L, Metcalf J, Liu S, Hallahan CW, and Connors M. The differential ability of help HLA B*5701+ long-term nonprogressors and progressors to restrict HIV replication is not caused by loss of recognition of autologous viral gag sequences. J Virol 2003; 77(12); 6889-6898. My Report? 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 physics gcse help Connors M. Diminished proliferation of install thesis HIV-specific CD4+ T Cells is associated with diminished IL-2 production and physics recovered by exogenous IL-2. J Virol 2003; 77(20); 10900-10909. Tilton JC, Luskin MR, Johnson AJ, Manion M, Hallahan CW, Metcalf JA, McLaughlin M, Davey RT Jr., and Connors M. Changes in derek paracrine IL-2 requirement, CCR7 expression, frequency, and cytokine secretion, of HIV-specific CD4+ T cells are a consequence of antigen load. J Virol 2007; 81;2713-2725.

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

Doria-Rose NA and Connors M. Physics Coursework Help? Antibody-secreting B cells in HIV infection. Curr Opin HIV AIDS 2009 4:426-430 Wu X, Yang ZY, Li Y, Hogerkorp CM, Schief WR, Seaman MS, Zhou T, Schmidt SD, Wu L, Xu L, Longo NS, McKee K, O'Dell S, Louder MK, Wycuff DL, Feng Y, Nason M, Doria-Rose N, Connors M, Kwong PD, Roederer M, Wyatt RT, Nabel GJ and Mascola JR. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 2010 329:856-861. A Problem Driver? Migueles SA and Connors M. Help? Long-term nonprogressive disease among untreated HIV-infected individuals: clinical implications of understanding immune control of HIV. JAMA 2010 304:194-201. [Redacted publication in press] The research direction of the HIV-Specific Immunity Section of the Laboratory of pros cons wearing school uniforms Immunoregulation is focused upon mechanisms of immunity to physics help HIV. Bruening Thesis? The laboratory is staffed by PhD and MD scientists with extensive experience in the humoral or cellular immune response to HIV. In addition we have close collaborations with investigators at the NIAID Vaccine Research Center in the area of coursework help structure-function relationships of HIV-specific antibodies.

Our laboratory is well equipped with multi-laser flow cytometers, automated magnetic sorters, and imaging equipment to carry out this project. Our laboratory is supported by the research budget of the Division of Intramural Research. Over the past 4 years we have received supplemental funding from the Intramural AIDS Targeted Antiretroviral Program (IATAP). This will continue for the next 2 years. We have also received funding from the Office of AIDS Research for work on writing graduate the humoral response to HIV. Positions and coursework 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 solve a problem Infectious Disease, Imperial College London, London UK 2003 - Professor of immunology, Department of Pathology, University of Oxford, Oxford UK. Other Experience and physics gcse Professional Memberships. 1995 - Member, American Association for the Advancement of Science 1998 - Member, American Society for pros cons school, Microbiology 1998 - Member, British Society for physics, Immunology, UK 1998 - Member, Society for General Microbiology, UK 2005 - Member of the Pasteur Institute Paris France Scientific Evaluation Committee. 2005 - Member of the Vaccine Research Center (VRC) NIH Board of Scientific Councilors 2007 - Member of BMGF Vaccine Monitoring Centre SAB 2008 - Member of NIH HIVRAD/Novartis Neutralizing Antibody Vaccine Consortium SAB 2009 - Member of study section for Swedish Program for International Development 2010 - Member of NIH study section for thesis, the B cell Immunology Partnership Program for HIV-1 Vaccine Discovery (U19) C. Coursework? Selected Peer-Reviewed Publications. Most relevant to the current application.

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

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

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

Requirement for an intact actin and tubulin cytoskeleton for efficient HIV-1 assembly and & Editing spread. Help? J. Virol. 81: 5547-6 Jolly C and Sattentau QJ. A Problem? 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. Physics Help? J. Write? Exp Med. Physics Coursework Help? 199: 283-193. Additional recent publications of important to the Field (in chronological order)

Wegmann F, Krashias G, Luhn K, Laamanen K, Vieira S, Jeffs SA, Shattock RJ and Sattentau QJ (2011) A novel strategy for inducing enhanced mucosal HIV-1 antibody responses in an anti-inflammatory environment. PlosOne 6: e15861. Install Thesis? 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. Physics Gcse? Aug 25th epub. Krashias G, Simon K, Wegmann F, Kok WL, Ho LP, Stevens D, Skehel J, Heeney JL, Moghaddam AE and install thesis Sattentau QJ. (2010). Potent adaptive immune responses induced against HIV-1 gp140 and influenza virus HA by a polyanionic carbomer.

Vaccine 28: 2482-2489. Zanetti G, Briggs JAG, Grunewald K, Sattentau QJ and Fuller SD. SIV spike glycoprotein structure in 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 actual PDF forms. The attachments are included below. In the physics gcse original version, these attachments met the page limits.] Understanding the basis of an immune response that controls infection or provides sterilizing immunity remains a major goal in the search for effective vaccines or immunotherapies for HIV.

Antibodies (Abs) induced by survey 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 physics gcse help 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. A Problem Ati Graphics? Antibody-dependant cellular cytotoxicity (ADCC) has been shown to physics gcse help mediate sterilizing immunity against challenge with pathogenic simian immunodeficiency virus [Hessel 2007]. Install Thesis? 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 gcse coursework deliver granzymes which induce apoptosis in the target. We want to study ADCC in on my survey infected patients to physics coursework help 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 graduate school 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 physics help disparate from classical neutralization. Proofreading & Editing? Finally we will use microscopy to examine the synapse between effectors, Abs, and targets. The outcome of coursework help this research will provide insight into the characteristics of Abs that mediate ADCC that are likely important goals in the design of HIV vaccines or immunotherapies.

Hypothesis: Antibody-dependent cellular cytotoxicity (ADCC) is a function that has been shown to mediate protection from lentiviral infection. We hypothesize that variations in Proofreading & Editing ADCC activity of sera are dictated by gcse coursework help the amount, specificity, and subclass of Proofreading HIV-specific antibodies. Aim 1 : Characterize the potency of physics coursework sera of HIV-infected individuals in install thesis ADCC. In ADCC, Abs bind viral epitopes that are presented by physics gcse help infected CD4+ T cells. NKs expressing an Fc receptor bind the Fc domain of the Proofreading & Editing Ab and use perforin to deliver granzymes to the HIV-infected cell. Subsequently, granzymes induce apoptosis within the cell. Our lab has developed a flow cytometric assay that measures granzyme B delivered to an HIV-infected CD4+ target T cell. We will classify ADCC by the percent of target cells receiving granzyme and the elimination of targets as defined by residual percent of gcse coursework help targets expressing p24, HIV capsid. Compare the serum of HIV+ individuals with various rates of progression and viral loads to determine which contain Abs capable of mediating the highest levels of my report on my ADCC. Compare the ADCC and physics help neutralizing activity of patient sera. Aim 2 : Characterize the install thesis specificity and coursework breadth of antibodies with ADCC activity.

Our laboratory has panels of NAbs derived from patients with known serum neutralizing or ADCC-mediating activity. Determine whether recognition of specific epitopes is required for ADCC. My Report Survey? Define the breadth of the gcse coursework polyclonal sera by its ability to install thesis mediate ADCC in CD4+ T cells infected by different clades of HIV. Physics Gcse Coursework Help? Titer serum total IgG, IgG1, and IgG3 binding infected CD4+ T cells. Aim 3 : Characterize the structure and function of the target-effector synapse. Using both fixed and live cell laser scanning confocal microscopy (LSCM), transmission electron microscopy (TEM) and cryo-electron microscopy (cryo-EM) and tomography, we will examine the nyu creative graduate synapse formed between NK and other cells with potential ADCC activity (macrophages and neutrophils) and infected target cells.

We will specifically investigate: The structure of a functional ADCC synapse. Coursework Help? The kinetics of derek thesis 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 current antiretroviral therapy, there is an imperative need for a vaccine.

One of the most critical areas of help research on vaccines for HIV is the search for correlates of immunity. At present the only method for determining the potential benefits of a vaccine with regard to protection from pros cons essay infection or lowering of physics help viral load upon write my report on my survey 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 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). 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 physics gcse coursework bind the Fc? region of these Abs. Upon cross-linking of the & Editing Fc? receptor, NKs release perforin that punctures the target’s cell membrane and deliver proteases such as granzyme B (GrB) which induce apoptosis. ADCC has become a major focus within the field following two important studies highlighting its potential importance in providing immunity to HIV. Coursework Help? 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 nyu creative writing preventing infection than neutralization or complement activation alone 4. Prior to this study, it was widely accepted that infection of a single cell would lead to integration and coursework 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 pros cons uniforms ADCC as an important component of vaccine induced immunity to HIV. In September 2009 data from the phase III RV144 (Thai) vaccine trial were released and help showed that the prime-boost combination of ALVACR HIV and AIDSVAXR B/E reduced HIV infection. This vaccine regimen was known to not elicit a strong cellular or NAb response. Solve Ati Graphics? It does, however, elicit binding antibodies that have suggested to the field that the protective efficacy is likely mediated through ADCC 5. Our laboratory is physics gcse coursework help 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 nature of an cons school effective ADCC response have not been addressed. For example, the physics coursework 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 write on my individual patients that permit a characterization of individual antibodies that mediate HIV-specific ADCC. One of the initial goals of physics help this project was to adapt our current killing assay to provide a more robust assay for Proofreading & Editing, HIV-specific ADCC. Past studies of ADCC have been hampered by the availability of assays that are only physics help 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. Nyu Creative Writing School? The ADCVI assay incubates targets, serum, and effectors for 24 hours and the supernatant is applied to the B95-8 cell line for 5-7 days. Physics Coursework? The endpoint is reduction of writing viral infection of the B95-8 cells 8. Physics Gcse Help? This method measures inhibition of viral production and subsequent infection but its disadvantages lie in the length of the assay and failure to school measure killing of infected cells. Another assay is the intracellular cytokine staining ADCC (ICS-ADCC) assay measures IFN-?, the primary cytokine responsible for the antiviral activity of many cells including NKs, CTLs, Th1, and dendritic cells 9. The advantages of this assay are that multiple effector functions can be measured and all cells and Abs are from the gcse same patient, but it is still a proxy that does not measure HIV-infected cell killing. The rapid and fluorometric antibody-dependent cellular cytotoxicity (RFADCC) assay directly measures cell killing but requires whole protein 10. While use of protein pulsed targets is a sensitive method, it likely places artificially high amounts of 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 Proofreading autologous NKs as effectors. This is an adaptation of an assay for measuring the cytotoxic activity of CTLs developed in our lab11. This assay measures the cleavage of physics help a GrB substrate, and eliminates background cell death using a Live/Dead stain to produce accurate quantitative and highly reproducible results. In brief, CD4+ T cells are stimulated for 3 days and HIV infected.

Autologous, negatively selected NKs are used as effectors. Wearing School Uniforms Essay? Effectors and coursework targets are labeled with surface dyes so that they can be discriminated. Derek Thesis? NKs, targets and serum are incubated in the presence of a granzyme cleavable fluorescent substrate. Physics Gcse Coursework Help? 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). Some infected cells show downregulation of ati graphics CD4 (PE-Cy7). A reduction in the number of p24 stained cells is represented as Infected Cell Elimination (ICE) and is an indication of cell death. In the example above, ICEInfected+Effectors+Serum = [(58.2-25.8)/58.2] x 100 = 54.9%.

There are several advantages to gcse coursework help this assay over older assays that use mismatched cell lines. Pros Cons Wearing Uniforms Essay? Because NKs lyse target cells in the context of MHC mismatch and cause nonspecific killing, autologous cells are used in our assay to reduce background. 12. Coursework? In addition, because NK function is install thesis diminished in HIV-infected patients, we use the NK cells and CD4+ T cell targets from uninfected patients in our assay as a readout for coursework, the effectiveness of a given serum sample in mediating ADCC 13, 14. My Report Survey? We observed variations in NKs from normal individuals in physics coursework their ability to mediate ADCC and a problem with choose donors that provide optimal signal to noise ratio that we will use to gcse coursework compare the serum of HIV+ individuals (Figure 2). The targets used in this assay are likely closer to the in vivo situation given autologous HIV-infected targets are used in the place of antigen pulsed cell lines. Other advantages include our assay’s ability to measure the mechanism of ADCC (granzyme delivery) and the outcome (death of infected cells) (Figure 2). MHC-1 is cons uniforms down-regulated in physics help virally infected cells, and the loss of MHC-mediated killer inhibitory signals permit NKs to kill a cell 15, 16. Install Thesis? We control for physics coursework help, this by my report on my measuring the granzyme content of physics coursework targets that are incubated only with effectors and sera from HIV-uninfected volunteers. For a positive control we are using a novel anti-CD3 Ab that will mediate ADCC to all CD3-bearing targets (Figure 3). With this Ab we have already demonstrated (1) the sensitivity and dynamic range with which we are able to & Editing measure ADCC, (2) Abs mediate ADCC in physics a dose dependent manner, and (3) GrB delivery is proportional to install thesis cell death.

Aim 1: Characterize the magnitude of ADCC in HIV infected individuals . Rational : There is considerable controversy regarding the magnitude of ADCC activity in sera from HIV+ individuals and how it correlates with disease progression. Help? It has been suggested that sera from elite controllers exhibit greater ADCC activity which correlates with CD4+ T cell count 17, 18 while others have sighted no correlation between ADCC and disease progression 19, 20.We will compare the serum of install thesis HIV+ individuals with various rates of progression and viral loads to determine which contain Abs capable of mediating the highest levels of ADCC. We will also compare the ADCC and neutralizing activity of physics gcse coursework patient serum to evaluate whether or not ADCC and neutralization always occur together in solve with ati graphics 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 physics coursework compare multiple indicators of immunity with ADCC.

Expected Outcomes/Interpretation : Based on bruening in vitro and passive transfer macaque studies, we expect LTNPs to coursework exhibit greater ADCC than progressors. Our current knowledge attributes LTNP delayed progression to install thesis superior CTL cytotoxicity but our data may show ADCC also to be a significant factor 11. Potential Complications : We do not foresee any difficulties in physics coursework help accomplishing this objective. Aim 2: Characterize MAb from serum identified as having potent ADCC activity with regard to 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 Proofreading patient derived MAbs to probe specificities required for ADCC. An ideal HIV vaccine would be able to protect against diverse virus strains so it is important to determine whether Abs raised against one clade of physics gcse help virus would be able to derek bruening mediate ADCC in CD4+ T cells infected by physics gcse different clades. Graduate School? We will use multiple strains of virus from clade A/E, B, and C to infect CD+ T cells and compare killing of target cells in the presence of serum pooled from clade B HIV+ patients. IgG1 and IgG3 are the predominant IgG isotypes with roles in ADCC. Gcse Coursework? It is possible that variations in 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 solve a problem driver, the same dilutions used in gcse help our killing assay, and measure total bound IgG, IgG1, and install thesis IgG3 by flow cytometry.

We believe flow cytometry is a better way of gcse measuring titers of install thesis binding Abs as compared to ELISA because Abs will recognize all possible epitopes on the surface of an infected cell in physics gcse help 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 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. Nyu Creative Graduate School? To date there has been no study using microscopy to investigate ADCC in physics help 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. Install Thesis? With fluorescent microscopy they observed after 1 hour of gcse incubation that 24% targets had formed conjugates with CD8+ T cells although many more cells had lysed. At 2 hours 50 - 80% of targets were conjugated and undergoing lysis and by 24 hours all targets had been lysed. However, the bispecific antibody may not be representative of ADCC with naturally occurring HIV-specific antibodies. In addition, the structure of the nyu creative writing graduate NK to HIV-infected target synapse was not examined.

Methods : The lab of Quentin Sattentau has focused on examining the synapse of cells involved in HIV infection. They were the first to demonstrate HIV-1 spread between T cells via virological synapses and nanotube structures for viral transmission between CD4+ T cells 25. Coursework? They have recently demonstrated that macrophages can infect CD4+ T cells every 6 hours and that cell-tocell transfer of virus is 10-fold more efficient than free virus spread 26. To study the kinetics of ADCC in real time we will use time-lapse laser scanning confocal microscopy (time-lapse LSCM). Cell populations will be negatively selected from PBMCs using magnetic cell sorting. Install Thesis? HIV-infected CD4+ T cells will be mixed with patient serum or Abs of multiple specificities (see Aim 2) and NKs to physics gcse evaluate ADCC; or neutrophils/monocytes to evaluate antibody-dependent cell-mediated phagocytosis (ADCP) and applied to poly-L-lysine coated cover slips. Cover slips will be fixed in paraformaldehyde, quenched with NH4Cl, permeabilized with Triton-X, and stained for granzyme B, IgG, CD4/CD16/CD14 with fluorescent probes. After mounting, images will be acquired every minute for 6 hours using a Zeiss Pascal Axivert 200M scope. We will use transmission electron microscopy and tomography (TEM) to generate higher resolution static images of the on my survey ADCC functional synapse.

For TEM targets, serum, and effectors will be incubated for approximately 1 hour, fixed in coursework paraformaldehyde and glutaraldehyde, and stained with osmium tetroxide. Samples will be embedded in epoxy resin, cut, and pros cons 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 gcse help, this research. Expected Outcomes : We expect to 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 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 the field of HIV-specific immunity. We are very well positioned to writing graduate 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 physics gcse NIAID IRB-approved protocol 02-I-0086. Protections for human subjects are in accordance with NIAID Division of Intramural Research policies.

Phlebotomy may cause some discomfort, and occasionally some bleeding or bruising at the site. On rare occasions, people faint while having blood drawn. Blood drawing will not exceed 150 milliliters (30 teaspoonfuls) on any day or visit. In the course of any time frame during this study, the total amount of blood will not exceed 10.5mL/kg, or 550 milliliters over any 8-week period, which is nyu creative graduate within the safety guidelines for blood drawing practiced at the Clinical Center. Like standard phlebotomy, leukapheresis is occasionally associated with local bleeding and bruising at the site of physics gcse coursework needle insertion. Lightheadedness can also occur, and people faint on rare occasions. & Editing? Occasional tingling in physics gcse coursework 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 & Editing Women and Minorities. Gender, Ethnicity and Race Consideration.

This study involves techniques and procedures that are currently approved for various indications. Male and female adult patients (18 years of age or older) will be enrolled without preference to gender, race or ethnicity from the gcse 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 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 nyu creative writing graduate school continuing HAART therapy, in the setting of a documented virologic and/or immunologic response. Patients who do not fully comprehend these potential risks of physics gcse HAART cessation, in the opinion of the study team, will not be offered participation in the study.

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

The safety of discontinuing antiretroviral therapy has not been established during pregnancy and nursing, and physics gcse coursework current guidelines continue to write on my survey advise HIV-positive women to take antiretroviral therapy to prevent viral transmission to the child during that time period. Therefore, pregnant or nursing women will be excluded from this study. Any woman of physics gcse coursework help childbearing potential must have a negative pregnancy test within two weeks prior to study entry. All participants who engage in install thesis 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 physics coursework help Quentin Sattentau as two HIV researchers with whom I would like to Proofreading train with because of physics their focus on write my report HIV immunology, vaccine design, and their expertise in basic immunology techniques, flow cytometry, and microscopy. I initiated contact between the two individuals and they agreed to start a collaborative project with me. After studying NAbs with Mark Connors for gcse help, one summer I decided I wanted to focus on antibodies that mediate ADCC. Pros Cons Wearing School? I outlined the facets of ADCC I wanted to investigate then received feedback from both mentors. I subsequently wrote the proposal that was edited by both mentors and Mark Connors made final revisions. I meet multiple times during the physics gcse week with Dr. Ati Graphics Driver? 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 meet at conferences. Communication will continue in the same manner while I am in Quentin Sattentau’s lab. Selection of Sponsors and Institution. Selection of Institution.

I decided to join Columbia’s MSTP program because of gcse coursework help its tradition of install thesis exemplary medical education, medical research, and unparalleled support offered to students from program administrators. Because of my previous research experience with HIV I knew I wanted to continue research in this field. I decided to join the 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. Physics Coursework Help? 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 graduate school 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 physics coursework help immediately implement them into my research. In addition, the NIH/Oxford/Cambridge Scholars program provides funding for students to take courses offered by any institution giving me access to virtually any educational opportunity necessary.

In addition, through 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 pros cons wearing school essay 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 physics coursework, NIH and one at a university. When I joined the program I searched for HIV investigators throughout NIH and Oxford and identified Mark Connors and Quentin Sattentau as potential mentors because I wanted to conduct research that had direct implications in vaccine development. Quentin Sattentau was studying how to nyu creative writing graduate school elicit effective anti-HIV neutralizing Abs (NAbs) for coursework help, vaccines and adjuvants to install thesis stimulate systemic and mucosal immunity. Through my search at the NIH I identified Mark Connors as a potential collaborator though he and physics gcse coursework Quentin had never collaborated before. I believed Dr. Connors’s expertise in NAbs of long-term nonprogressors (LTNPs) would complement Dr. Sattentau’s vaccine development goals. In addition, Dr. Connors’s unique cohort of LTNPs would provide ready access to samples to Proofreading & Editing study many facets of HIV infection. Finally, I believe Dr.

Sattentau’s approach to research as a PhD and physics help Dr. Connors’ as an MD will teach me to think about write on my, science in a more practical way that is suited to me as a future MD/PhD researcher. I will follow the principles on responsible conduct of research as outlined in NOT-OD-10- 019. Physics Gcse Coursework Help? As an undergraduate at bruening thesis, UMBC I took a semester-long course entitled “Ethics/Integrity in Scientific Research” which first help me to understand the responsibility scientists have to one another and medical community honestly share information. As a Columbia medical student, I have taken the Hippocratic Oath to gcse coursework help guide my patient care and Proofreading & Editing I am expected to adhere to the code of ethics as outlined in student handbook. Coursework Help? Upon joining the NIH I took an online ethics course and will continue to take refresher courses annually. Write Survey? At Oxford I will continue my ethics training by taking the required “Ethics: Introduction to Research Ethics”. Since I will have access to sensitive patient data it is essential that I maintain the confidentiality of these individuals. Physics Gcse Help? When I started research at NIH I participated in a problem with driver a patient confidentiality seminar.

Oxford offers an “Ethics: Confidentiality” course in which I will enroll to better my further my understanding and ability to maintain ethical practices with regards to 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 help, the interface of write my report on my survey medicine and science, I have endeavored to physics help earn an MD/PhD. I believe that the solve a problem with combined degree’s greatest value lies in the perspective that it affords: to approach patient care with a researcher’s eye, and to approach research with a physician’s focus on improving the quality of physics coursework help life. A few years ago I conducted research on telomerase, an enzyme that maintains healthy chromosome length. Derek Bruening? 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 telomerase and measuring their growth rates, I noticed two things.

The first was that cells with low levels of telomerase grew slowly. Secondly, these cells had abnormal morphologies, as do tumor cells. These observations led me to wonder whether the progression of cancer in help individuals with DC was slower than in patients without it because DC patients have less active telomerase. Bruening Thesis? Upon discussing this with my P.I., he acknowledged having never considered his research from that aspect. A literature search demonstrated a lack of help any substantial research concerning this question. Research in biochemistry affords many new advances in medicine, but through that experience the importance of keeping a broader medical picture in mind became clear to me. My goals as a physician scientist are to treat patients and conduct research that will allow me to solve a problem with ati graphics impact patients I will never meet through therapeutic discovery; specifically serving as a creative link between science and physics gcse coursework help 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 a problem ati graphics even through this grant. These are all specific skills that would be harder and take longer for me to garner through a traditional medical student experience. Coursework Help? 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 uniforms essay 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. Physics Gcse Help? Connors. We also have phone conferences and meet with Dr. Sattentau at numerous conferences throughout the year. Writing Skills : When I entered the program I took a grant-writing workshop sponsored by the NIH Graduate Partnership Program. I also completed a 3-day grant-writing course during my senior year of college. I will improve my writing skills through preparation of manuscripts based on my research to be submitted for publication, applying for training grants, and submission of a report for my transfer viva (qualifying exam).

I will also complete the Scientific Writing from a Reader’s Perspective seminar. Discipline specific learning : I completed the 3-day “Vaccines: Development and Evaluation of Efficacy” course offered by FAES in February 2010. I also attended “Psychiatry and HIV,” a 2-day workshop offered by the American Psychiatric Association so I could learn to effectively interact with HIV+ patients I encounter. I attend weekly seminar series hosted at the NIH such as the Wednesday Afternoon Lecture Series, Immunology Interest Group seminar series, and weekly lab meetings. Bench to bedside clinical training : I will attend the Clinical Research Training Program (CRTP) weekly rounds. I will also have the opportunity to be mentored by bruening an infectious disease clinician. Presentations : I will continue to annually attend and present at physics help, pertinent Keystone Symposia and the Annual AIDS Vaccine conference.

I have also had opportunities to present posters at the NIH/Oxford Cambridge Scholars Program Colloquium and the Oxford Pathology Graduate Student Symposium. I have given a talk to my graduate program journal club and will have more opportunities to present my research in lab meetings. Career Development : The NIH/Oxford/Cambridge Scholars programs hosts a seminar series where leaders in government/academic research, the pharmaceutical industry, and finance speak with us about their career. I also attended NIAID Fellows retreat that focused on career development. Teaching : As I prepare to leave the bruening lab I will be responsible for training a new research fellow. Year 1 (continued) and Year 2: Quentin Sattentau Lab (Oxford) Research 75%, Seminars/Courses 10%, Presentation/Career Development/Clinical 10%, Teaching 5% Research Skills : While working in physics coursework help Quentin Sattentau’s lab I will learn to apply microscopic imaging to studying HIV infection. Nyu Creative Writing Graduate? I will have weekly meetings to discuss my research progress.

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

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

Because of my accomplishments that summer, I was invited to my report on my participate in an extension of the Gene Search Program during my 12th grade year. This program inspired me to pursue a career in gcse coursework biomedical research because I began to install thesis understand how the principles I was learning in physics coursework help school fostered scientific discovery. As a high school senior, I worked with Dr. Writing Graduate? 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 physics gcse help hemoglobin for oxygen, thereby facilitating oxygen release to tissues. Patients suffering with sickle cell anemia have high levels of Proofreading & Editing 2,3- DPG. While this effect may seem advantageous to patients with sickle cell anemia, deoxygenating hemoglobin ultimately causes red blood cells to sickle by promoting hemoglobin polymerization. Previous studies indicated that adenosine might regulate 2,3-DPG levels through an gcse coursework help interaction with the & Editing A3 receptor. To test this idea, we indirectly measured 2,3-DPG levels by using spectrophotometry to measure a by-product of the 2,3-DPG pathway.

An exciting therapeutic prospect of our research is that an gcse coursework antagonist of the A3 receptor may prevent the on my survey accumulation of 2,3-DPG and gcse coursework help RBC sickling in patients with sickle cell anemia. I documented this work in a five-chapter thesis, in accordance with my high school’s Science and Technology Program, and presented it at school, my school’s science fair, where I was awarded third place in biochemistry. During college I spent four years working with Dr. Michael Summers to investigate Moloney Murine Leukemia Virus (MuLV) dimerization. Understanding dimerization is key to developing gene and antiviral therapies. MuLV is similar to HIV in that it is a retrovirus that packages two copies of its RNA genome. Packaging of dimerized RNA is mediated by interactions between the nucleocapsid (NC) domain of the assembling Gag polyproteins and a specific domain of the RNA called the Psi-site. Previous work in the Summers lab suggested a riboswitch mechanism for physics gcse coursework help, MLV genome packaging, where, in solve a problem ati graphics monomeric RNA, Psi-site UCUG segments capable of binding NC are sequestered by base pairing, but upon dimerization, become exposed to gcse coursework bind NC.

My project was to investigate whether similar sequences in solve with ati graphics driver the Psi-site could also bind NC. Using isothermal titration calorimetry and nuclear magnetic resonance, we identified short RNAs (ACAG, UUUG, and physics coursework UCCG) that bind NC with nanomolar affinity. My Report? 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 gcse help which three nucleotides lie upstream of the guanosine. & Editing? The paper I co-authored (Dey, A., et. al., 2005) extends an established model for genome recognition, in which the NC domains of assembling Gag molecules interact with multiple X(i-3)-X(i-2)-X(i-1)-G(i) elements (X is a variable nucleotide) that appear to 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 physics RNA dimers which was also confirmed by equilibrium dialysis. Most recently our lab published the NMR structure of my report survey this dimer (Miyazaki, Y., et al., 2010). During the gcse summer of install thesis 2005 I participated in the Weill Cornell/Rockefeller/Sloan Kettering Gateways to the Laboratory Program. I worked with Dr. Nikola Pavletich toward solving the crystal structure of the Saccharomyces cerevisiae Rad4-Rad23 complex bound to a DNA substrate. Rad4-Rad23 is a homolog of human XPC-HR23B, a DNA damage-repair protein. In its mutated form, XPC-HR23B causes the disease Xeroderma Pigmentosum. Gcse Help? 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 the 2005 SACNAS National Conference. In 2006 I studied telomerase assembly in the lab of Dr. Thomas Cech at install thesis, the University of Colorado at Boulder. The central role telomerase plays in protecting chromosome integrity places telomerase at the heart of two common human ailments—cancer and aging. To study how and where in the cell telomerase is assembled from its RNA and protein components, we used the budding yeast Saccharomyces cerevisiae as a model organism. We sought to physics understand whether the noncoding telomerase RNA (TLC1) goes through a cytoplasmic phase during its biogenesis. One model is that a polyadenylated precursor form of TLC1 is thesis exported to the cytoplasm where it associates with Sm proteins. Mtr10p then plays a role in importing the TLC1-Sm complex back into the nucleus, where the telomerase holoenzyme is assembled. Using cellular fractionation and real-time RT-PCR, we attempted to physics gcse localize TLC1 in write my report survey its various stages.

During the summer between my first and second year of medical school I joined the lab of Mark Connors where I screened patient sera for breadth and help potency of neutralizing Abs against HIV using a TZMBL neutralization assay. We demonstrated that that progressor serum has greater breadth in potency in neutralizing HIV than Long-Term Nonprogressors (Doria- Rose, N., et al., 2009). Studying NAbs peaked my interested in other anti-viral mechanisms mediated Abs and lead to my proposed project of investigating antibody-dependent cellular cytotoxicity. Each research experience has shown me the many nuances of install thesis a research career. I learned about: 1) the importance of basic research in gcse help developing medicines, 2) the time, organization, and pros wearing school ingenuity it takes to coursework help conduct research, and 3) the write on my vital role that a physician-scientist plays in translating basic research into medical treatment. Although I’ve experienced frustrations and disappointment in research, the thrill of physics help observing something new, finishing a project, or publishing a paper always outweighs these challenges. Proofreading? Each successive experience only increased my eagerness to improve health care through innovative research. [Redacted from sample.] QUENTIN SATTENTAU MENTOR STATEMENT. [Redacted from sample.] [Our Web version of this sample application can't reproduce the 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 physics coursework Postdoctoral. RESUME AND SUMMARY OF DISCUSSION: In this application, the fellowship candidate proposes to bruening investigate antibody-dependent cellular cytotoxicity (ADCC) in HIV-infected patients do determine the extent of protection that ADCC provides. The reviewers noted that the candidate is outstanding, with a strong record of help research training and accomplishment. The candidate appears to be highly motivated. Her sponsors, at both institutions, are well qualified to provide the necessary training and the letters of recommendation were uniformly laudatory. Solve A Problem? Minor weaknesses of the gcse help application included the driver ambitious research plan to be accomplished in two years, the risk of conducting the research at two sites, and the failure to address pitfalls and alternatives of the research project. Physics Coursework Help? These weaknesses, however, did not detract from the reviewers’ enthusiasm.

This training project will have a high impact in ensuring that the derek candidate maintains her potential to gcse become an Proofreading independent clinical researcher. DESCRIPTION (provided by applicant): Understanding the basis of an immune response that controls infection or provides sterilizing immunity remains a major goal in the search for effective vaccines or immunotherapies for HIV. Physics Gcse Coursework Help? 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 install thesis primary goal in most recent vaccine trials. However, this approach has not been successful in containing viral replication in physics help 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 Proofreading the target. We want to coursework help study ADCC in infected patients to understand the magnitude and pros 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 gcse coursework help patients with the most ADCC, generate monoclonal Abs (mAbs), and characterize the write on my survey mAbs based on epitope specificity, affinity, potency, breadth, IgG isotype, and Fc type. Physics Help? We will also evaluate whether ADCC is disparate from with ati graphics classical neutralization. Finally, we will use microscopy to physics help examine the synapse between effectors, Abs, and targets. Pros Cons Wearing School Uniforms? The outcome of this research will provide insight into the characteristics of Abs that mediate ADCC that are likely important goals in the design of HIV vaccines or immunotherapies. Hypothesis: Antibody-dependent cellular cytotoxicity (ADCC) is a function that has been shown to mediate protection from physics gcse lentiviral infection. We hypothesize that variations in ADCC activity of sera are dictated by install thesis the amount, specificity, and coursework subclass of HIV-specific antibodies.

Aim 1: Characterize the potency of sera of HIV-infected individuals in my report on my survey ADCC. Aim 2: Characterize the physics coursework specificity and pros cons essay breadth of antibodies with ADCC activity. Aim 3: Characterize the gcse coursework help 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 nyu creative writing 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 coursework 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 install thesis from an 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. Gcse Coursework Help? Ultimately, she will receive her Ph.D. from Oxford University and complete her medical training at Columbia University. On My Survey? The applicant is highly recommended by previous research mentors and has an coursework outstanding academic record. Her research experience, which includes four years of undergraduate research, is matched by her productivity; she is a contributing author on two published papers and has presented her work at numerous scientific venues.

The research plan, which derives directly from the expertise and interests of the mentor, focuses on relationships between antibody-dependent cellular cytotoxicity (ADCC) in derek bruening thesis HIV-1-infected patients, HIV-1-associated disease progression, and antibody subtype. Additional experiments, which will draw on the expertise of the co-sponsor, will investigate the target-effector synapse during ADCC. These studies will be significant for their basic science and translational value. The training plan is unique in that training and research will be accomplished in physics gcse coursework help two separate laboratories of the sponsor and co-sponsor. This proposal outlines an writing school excellent training opportunity that will greatly benefit the physics help applicant and cons wearing uniforms essay her potential for establishing an independent research career. The applicant, who is gcse currently enrolled in an M.D./Ph.D. training program, is install thesis described in coursework help three strong letters of recommendation as enthusiastic, articulate, knowledgeable, highly focused, and very inquisitive. Her undergraduate research mentor characterized her as “easily among the & Editing top two or three of the more than 200 current and former undergraduates” that he has mentored. Gcse? The applicant has four years of Proofreading & Editing undergraduate research experience, which involved work with the physics gcse coursework Moloney Murine Leukemia Virus, and research performed during a summer program at the Howard Hughes Medical Institute focused on studies of telomerase.

Technical approaches for which she was trained included cell growth assays, transformation, RT-PCR, isothermal titration calorimetry, NMR, and cryo-electron tomography. Through her prior research experience, the applicant has been included as a contributing author on two published papers and Proofreading has presented eight posters and one oral presentation at help, various local, national, and international meetings. The applicant has an outstanding academic record (3.97 GPA) and numerous awards and write survey recognitions reflecting superior academic performance. The collaborative project outlined in the proposal was an outgrowth of gcse coursework a dialog initiated by the applicant between the sponsor and co-sponsor. Write My Report On My? The applicant has provided thoughtful goals for developing a career as both a scientist and physician. 2. Sponsors, Collaborators, and Consultants:

The applicant’s mentor and sponsor, who is currently Chief of the HIV-Specific Immunity Section in the Laboratory of Immunoregulation, NIAID/NIH, is an established and productive senior investigator with research support provided by the NIH. The co-sponsor is also a productive researcher with a consistent record of physics support for studies related to thesis HIV/AIDS. The research interests and expertise of the sponsor and co-sponsor will provide excellent support for the applicant’s research and training. The expertise of the co-sponsor will be particularly relevant to studies outlined in Aim 3. The sponsor has trained an average of physics coursework help four students per year over 20 years, suggesting an excellent training environment for write on my, 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. trainees in the co-sponsor’s laboratory. The latter trainees will overlap with the applicant for gcse coursework, one year or more.

These interactions will enrich the applicant’s training. The research plan is nyu creative writing school 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 ADCC (Aim 1), the physics coursework help specificity and breadth of writing school antibodies with ADCC activity (Aim 2), and coursework the structure/function of the a problem with ati graphics target-effector synapse that mediates ADCC. The central feature of the physics gcse coursework help proposed research is a novel and quantitative ADCC assay (developed in the sponsor’s lab) that offers significant improvements over thesis other ADCC assays. Results generated from help experiments in Aims 1 and 2 will have both basic science and translational value, while results from Aim 3 experiments will provide basic information about the mechanisms of write my report on my survey ADCC. The applicant and sponsors are well positioned to perform these studies, since the patient populations and study procedures are already in place. The applicant is participating in gcse the NIH/Oxford/Cambridge Scholars Program, which promotes research with a mentor at the NIH and another mentor at derek, a university. Consistent with the physics Scholars Program, the research training plan includes studies and training in install thesis year 1 in the sponsor’s lab at the NIH, continued studies and physics gcse coursework help training in year 2 in the co-sponsor’s lab at Oxford, and years 3 and 4 in medical school. Install Thesis? Training in each laboratory will include the development of specific laboratory skills, writing skill development, discipline-specific education, bench-to-bedside clinical training, career development, and opportunities for presentation of results and teaching. Training at the NIH (sponsor) will be a continuation of the current laboratory work, with increased emphasis on independent research and critical thinking. Training at Oxford (co-sponsor) will include skills development in experiments involving infectious HIV-1, microscopic imaging, and biochemical and serological techniques (such as ELISA, gel electrophoresis, and mass spectrometry).

Although the targeted patient enrollment is given as 300 HIV-1-infected individuals, the experimental plan does not provide details regarding the physics gcse coursework scope of school uniforms studies in Aim 1. Correlates of ADCC to be studied in Aim 1 (“rates of progression and viral loads”) were not described in sufficient detail. How will rates of progression be measured? Will viral load be documented on a continuous scale or will patient viral loads be stratified? An explanation of how the gcse 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 enhance the bruening capability of the applicant to develop an independent and productive research career. 5. Physics? Institutional Environment Commitment to Training: The resources and facilities at both institutions will provide outstanding environments for training and research. A more detailed plan regarding the coordination of training plans between the sponsor and graduate co-sponsor would be valuable, considering the distance and time difference between the two performance sites. Training in the Responsible Conduct of coursework Research:

Comments on Format (Required): The description of RCR training is brief and does not provide a detailed plan for formal training. However, enrollment in wearing essay two formal courses at Oxford (both focused on ethics) is mentioned. Comments on Subject Matter (Required): Training courses and physics coursework 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 install thesis RCR training. Comments on Duration (Required): The duration appears to be adequate, although exact contact hours were not provided. Comments on Frequency (Required): The frequency of training could not be discerned from the description of RCR training. Fellowship Applicant: 2.

Sponsors, Collaborators, and Consultants: 1. Research Training Plan: 2. Training Potential: 2. Institutional Environment Commitment to Training: 1. Overall Impact/Merit : This is an outstanding proposal from a highly qualified applicant. Gcse? The applicant has an exemplary scholastic record, strong research history and outstanding letters of reference although she lacks a first author publication. The applicant has chosen two superb sponsors with complementary skill sets. Graduate School? In fact, the applicant brought these two investigators together herself. Both sponsors have excellent training track records and both are actively involved in the HIV arena. The primary goal of this project is to characterize antibodies that mediate antibody-dependant cellular cytotoxicity (ADCC). Coursework Help? The Connors lab at install thesis, the NIH has developed a novel flow cytometric-based assay to measure granzyme B delivered to an HIV infected cells.

Using this novel assay the applicant plans to compare ADCC in HIV+ subjects with various rates of coursework disease progression and to define the specificity and install thesis breadth of antibodies with ADCC activity (Aim 1 and 2). The third Aim to characterize the help structure and function of the wearing uniforms essay target-effector synapse will be carried out at Oxford under the guidance of Dr. Sattentau. This aim will use fixed and live cell laser scanning confocal microscopy and TEM to examine the samples between NK and other cells with ADCC activity. If the physics gcse coursework applicant is successful the data from this project will be highly important for HIV vaccine development. Nyu Creative Writing Graduate? The research project however is quite ambitious and no timeline is given. It appears that the coursework help applicant plan to spend 1 more year in nyu creative graduate the Dr. Connors lab and 1 year in Dr.

Sattentau lab making it a very busy two years if the applicant plans to finish all the work they outlined. Despite the highly ambitious nature of the proposed research project the overall project goals warrant further study and the applicant herself is physics gcse coursework help of the highest caliber making this application worthy of & Editing 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 physics gcse coursework, UMBC she was a member of the Meyerhoff Scholars Program funded by the HHMI. & Editing? The applicant has coauthored 2 papers and is the physics first author on pros cons school uniforms essay 8 posters and 1 oral presentation. The applicant has extremely strong letters of recommendations, one of which is from physics gcse coursework help a Nobel Prize winner.

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

Sattentau, a Professor of Immunology and Pathology at the University of physics coursework 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 on my applicants proposed research project. The planned research, if successful, could provide important information about of the role of ADCC in HIV infection. Physics Gcse? The project is well outlined and there are sufficient preliminary data to derek thesis support the feasibility of the physics gcse help project. The plan is to utilize a novel recently developed (Connors lab) quantitative flow cytometric assay to measure GrB cytotoxicity and determine which Abs are capable of mediating the highest level of ADCC. Using this technique the thesis applicant plans to characterize the potency of help sera from subjects with different rates of disease progression, characterize the specificity and breadth of Proofreading antibodies with ADCC activity. Using advance microcopy techniques (fixed and live cell laser scanning confocal microcopy and electron microscopy) the physics 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. A Problem Driver? It may be difficult for the applicant to finish all the proposed work especially the coursework work proposed in Aim 3. The applicant is calling for 300 subjects but no power calculation is nyu creative writing graduate 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. Gcse Help? The plan includes research, writing skill (grant writing course), presentation, career development, teaching (both in class room training of new personnel) and discipline specific learning (i.e. in house courses and seminar series, lab meetings). Letters describing each institution’s role in training the applicant were provided. Pros Cons? Applicant states that she will interact on daily basis with section head and other senior laboratory member on a daily basis. Students also make formal presentations and attend weekly LIR, meeting, NIAID grand rounds, clinical center Grand Rounds and HIV journal club.

The training plan indicates that the applicant will be at the NIH for physics, one year and Oxford for one year and then back to medical school for the last 2 years. This raises some concerns regarding the nyu creative graduate duration of the funding (3 vs. 2 years). 5. Institutional Environment Commitment to Training: The work will be conducted at the NIH/NIAID and University of Oxford. Both institutions are of the highest caliber with access to physics help all the Proofreading required resources.

Oxford has a program in place for graduate students to take accelerated courses and coursework the NIH Foundation for Advanced Education in the Sciences also has specialized courses that will facility the applicants goal to become an infectious disease investigator. Training in the Responsible Conduct of Research: Comments on Format (Required): On line ethics course at the NIH and my report formal classroom course at Oxford. Comments on physics help 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 install thesis Duration (Required): Comments on Frequency (Required): Online course and annual refresher at the NIH. Additional Comments to physics coursework 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 write survey 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 Satentau (Oxford) and will complete her MD studies at Columbia. The primary hypothesis of gcse coursework this proposal is that ADCC activity levels in sera are dictated by the amount, specificity, and subclass of HIV-specific Abs. This represents a highly relevant area of research that will be tackled through 3 straightforward and well-planned aims – (i) characterize the potency of sera from individuals at different stages of HIV infection in ADCC (comparing to clinical status and Ab neutralization), (ii) characterize the specificity and breadth of Abs mediating ADCC (comparing the sera to panels of known neutralizing Abs), and (iii) characterize the ADCC synapse. Ati Graphics? This will involve state-of-art approaches established in the sponsors’ labs, allowing the applicant an physics coursework help excellent chance to perform this research.

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Concluding Lecture on Animal Farm. revolution after old Major dies, becomes tyrannical dictator of Animal Farm later, only physics coursework help interest power for self. Snowball – the other pig leader of Animal Farm after Old Major’s death , great military tactician, only has animals’ interest at heart, run off the farm by Napoleon. Squealer – Napoleon’s mouthpiece.

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Firearms on College Campus Essay Sample. There has been an on coursework going debate about whether or not college students and/or professors should be allowed to carry firearms on campus. The Law allows each state to determine if concealed weapons are allowed to wearing uniforms be carried on campus. Many advocates of firearms are in agreement that firearms should be allowed on campus. Gcse Help! In the past years, there have been shootings on college campuses that killed many and injured many. Allowing those who are licensed and derek bruening thesis, trained to carry firearms on campus would seemingly act as a deterrent to those who may have ill intentions and often are carrying illegal firearms. With the proper training and education on firearms, students and professors would have the ability to neutralize a potential threat and have the help ability to protect themselves and those around them. Understanding that it is the duty of law enforcement to protect all of our citizens, it has become very clear that they can not be everywhere and response time to a life threatening situation is not always ideal.

Many argue that students and professors on college campuses should maintain focus on education and that allowing firearms on campuses may cause distractions. Take the Virginia Tech massacre on April 16th, 2007(1) as an example. Nyu Creative Writing School! In two shooting sprees that happened roughly two hours apart, a student at the university shot and killed 32 people and wounded a number of others before turning the physics gcse help gun on thesis himself. If a trained and educated student or professor had been in gcse help possession of a firearm, many lives could have been saved. & Editing! There have been many debates about allowing students to carry firearms. Many of the physics coursework help most common debates about Proofreading & Editing why firearms should not be allowed on campus are easy to respond to: Answer: Studies* show that 90% of suicides are committed in the home. Because most college students over the age of twenty-one (the minimum age to obtain a concealed handgun license in coursework most states) live off campus, allowing concealed carry on college campuses would have very little impact on the ability of college students to possess firearms in their homes and, therefore, little to no impact on the overall number of graduate school suicides by coursework, college students.

*“Youth and Adolescent Suicide: A Guide for Educators,” Oregon Resiliency Project, University of derek thesis Oregon, 2003; After Suicide: A Ray of gcse Hope for Those Left Behind, Eleanora Betsy Ross, 2001 NOTE: At the University of Texas—a major university with over 50,000 students—a quick comparison of campus housing statistics and Proofreading & Editing, concealed handgun licensing statistics reveals that there would likely be no more than ten to twenty concealed handgun license holders living in on-campus housing [pic]Argument: Guns on campus would distract from the learning environment. Answer: Ask anyone in a ‘right to carry’ state when he or she last noticed another person carrying a concealed handgun. The word ‘concealed’ is there for gcse coursework help, a reason. Concealed handguns would no more distract college students from learning than they currently distract moviegoers from enjoying movies or office workers from doing their jobs. “In most states with ‘shall-issue’ concealed carry laws, the rate of concealed carry is about 1%. That means that one person out of 100 is Proofreading, licensed to carry a concealed handgun. Therefore, statistically speaking, a packed 300-seat movie theater contains three individuals legally carrying concealed handguns, and a shopping mall crowded with 1,000 shoppers contains ten individuals legally carrying concealed handguns. Students who aren’t too afraid to attend movies or go shopping and coursework, who aren’t distracted from learning by the knowledge that a classmate might be illegally carrying a firearm shouldn’t be distracted from learning by pros cons wearing uniforms, the knowledge that a classmate might be legally carrying a firearm.” Answer: The vulnerability of gcse help dorms to solve with ati graphics driver theft does not necessitate a campus-wide ban on concealed carry by licensed individuals. There are numerous other options, from community gun lockups to small, private gun safes that can be secured to walls, floors, bed frames, etc. NOTE: On most college campuses very few students of legal age to obtain a concealed handgun license still live in dorms.

Even at the University of gcse coursework Texas—a major university with over 50,000 students—a quick comparison of campus housing statistics and concealed handgun licensing statistics reveals that there would likely be no more than ten to twenty concealed handgun license holders living in on-campus housing. [pic]Argument: It’s possible that a gun might go off by accident. Answer: Accidental discharges are very rare—particularly because modern firearms feature multiple safety features and because a handgun’s trigger is typically not exposed when it is concealed—and only a small fraction of nyu creative writing accidental discharges result in injury. SCCC feels that it is wrong to deny citizens a right simply because that right is accompanied by a negligible risk. NOTE: Only about 2% of all firearm-related deaths in the U.S. Coursework Help! are accidental, and most of those are hunting accidents and accidents involving firearms being openly handled in an unsafe manner. A person is five times more likely to accidentally drown, five times more likely to accidentally die in a fire, 29 times more likely to die in Proofreading & Editing an accidental fall, and 32 times more likely to coursework die from accidental poisoning than to solve a problem with ati graphics driver die from an accidental gunshot wound.

Answer: Before shall-issue concealed carry laws were passed throughout the United States, opponents claimed that such laws would turn disputes over parking spaces and traffic accidents into coursework, shootouts. This did not prove to be the case. The same responsible adults—age twenty-one and above—now asking to be allowed to carry their concealed handguns on college campuses are already allowed to pros cons school uniforms essay do so virtually everywhere else. They clearly do not let their emotions get the better of them in physics gcse other environments; therefore, no less should be expected of them on solve a problem with ati graphics college campuses. [pic]Argument: The college lifestyle is defined by alcohol and drug abuse. Why would any sane person want to help add guns to that mix? Answer: This is NOT a debate about keeping guns out of the hands of college students.

Allowing concealed carry on college campuses would not change the rules about who can buy a gun or who can obtain a concealed handgun license. Every state that provides for pros school uniforms, legalized concealed carry has statutes prohibiting license holders from carrying while under the influence of drugs or alcohol. Legalizing concealed carry on college campuses would neither make it easier for college students to physics gcse obtain firearms nor make it legal for a person to carry a firearm while under the influence of drugs or alcohol. Allowing concealed carry on college campuses would have no impact on the laws regulating concealed carry at pros cons, bars and off-campus parties, the places where students (particularly students of legal age to obtain a concealed handgun license) are most likely to consume alcohol. Argument: In an active shooter scenario like the physics one that occurred at Virginia Tech, a student or faculty member with a gun would only make things worse. Nyu Creative Graduate! Answer: What is gcse, worse than allowing an execution-style massacre to Proofreading continue uncontested? How could any action with the potential to stop or slow a deranged killer intent on slaughtering victim after victim be considered ‘worse’ than allowing that killer to continue undeterred? Contrary to what the movies might have us believe, most real-world shootouts last less than ten seconds*. Even the real Gunfight at the O.K.

Corral, a shootout involving nine armed participants and a number of bystanders, lasted only coursework about thirty seconds and resulted in only three fatalities. It is unlikely that an install thesis, exchange of gunfire between an armed assailant and an armed citizen would last more than a couple of seconds before one or both parties were disabled. How could a couple of physics gcse coursework help seconds of exchanged gunfire possibly be worse than a ten-minute, execution-style massacre? Argument: The job of defending campuses against violent attacks should be left to the professionals. On My! Answer: Nobody is gcse coursework help, suggesting that concealed handgun license holders be charged with the a problem with duty of protecting campuses. What is being suggested is that adults with concealed handgun licenses be allowed to protect themselves on college campuses, the physics coursework same way they’re currently allowed to my report protect themselves in physics gcse coursework help most other unsecured locations. Argument: Police officers typically spend four to five months in training; whereas, concealed handgun license holders usually spend one day or less. Answer: Police officers do not spend four to bruening thesis five months learning to carry concealed handguns for physics gcse coursework, self-defense; they spend four to five months learning to pros be police officers. Concealed handgun license holders are not police officers; therefore, they have no need of most of the training received by physics gcse, police officers.

Concealed handgun license holders don’t need to know how to drive police cars at a problem, high speeds or how to kick down doors or how to conduct traffic stops or how to make arrests or how to use handcuffs. And concealed handgun license holders definitely don’t need to spend weeks memorizing radio codes and traffic laws. “Contrary to what some opponents of concealed carry might claim, concealed handgun license holders don’t need extensive tactical training because they are not charged with protecting the public—It’s not their job to act like amateur, one-man SWAT teams. All a concealed handgun license holder needs to gcse help know is how to a problem driver use his or her concealed handgun to stop an immediate threat of death or serious bodily harm, and physics gcse coursework, that type of training CAN be accomplished in a few hours.” NOTE: In some states, such as Texas, the shooting test for a concealed handgun license differs very little from the annual re-qualification test for police officers. Argument: How are first responders supposed to tell the difference between armed civilians and armed assailants? Answer: This hasn’t been an school, issue with concealed handgun license holders in physics gcse coursework other walks of life for several reasons. First and foremost, real-world shootouts are typically localized and over very quickly. It’s not realistic to expect police to encounter an ongoing shootout between assailants and armed civilians. Second, police are trained to expect both armed bad guys AND armed good guys—from off-duty/undercover police officers to armed civilians—in tactical scenarios. Proofreading & Editing! Third, concealed handgun license holders are trained to use their firearms for self-defense.

They are not trained to gcse coursework run through buildings looking for bad guys. Therefore, the biggest distinction between the wearing school uniforms essay armed assailants and the armed civilians is that the coursework armed civilians would be hiding with the write my report on my survey crowd, and the armed assailants would be shooting at the crowd. Answer: Among the thirty-six shall-issue’ states*—states where local authorities cannot require qualified applicants to “show a need” before the applicant is issued a concealed handgun license/concealed carry weapons permit—six states allow, without special provision, for gcse help, any qualified person eighteen years or older to a problem with driver be issued a concealed handgun license. These states are Indiana, Maine, Montana, New Hampshire, North Dakota, and South Dakota. “Based on the FBI/Department of Justice violent crime statistics for the year 2006, the crime rates for these seven states, when ranked with all fifty states and the District of Columbia, rank as follows: • Indiana – 30. • South Dakota – 47. • New Hampshire – 48. • North Dakota – 50. “Not only are Maine, North Dakota, New Hampshire, and South Dakota four of the gcse five** U.S. states with the lowest crime rates, Montana has the tenth lowest crime rate, and Indiana isn’t even in the top 50%. Clearly, these states’ lenient concealed handgun laws are not breeding generations of install thesis young violent offenders. “The extraordinarily low crime rates in these six states, coupled with the gcse coursework fact that these states have a combined population of only about 10,900,000 (approximately 1.6 million less than the combined population of America’s two largest cities—New York, NY, and Los Angeles, CA—and at approximately 1/3 the combined violent crime rate of solve a problem ati graphics those two cities) has led Students for Concealed Carry on Campus to focus on the majority of ‘shall-issue’ states where the minimum age to receive a concealed handgun license is twenty-one.” *Alaska (licenses are offered but not required to carry a concealed handgun), Arizona, Arkansas, Colorado, Florida, Georgia, Idaho, Indiana, Kansas, Kentucky, Louisiana, Maine, Michigan, Minnesota, Mississippi, Missouri, Montana, Nebraska, Nevada, New Hampshire, New Mexico, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, South Carolina, South Dakota, Tennessee, Texas, Utah, Virginia, Washington, West Virginia, Wyoming **Vermont is ranked at 49—the third least violent state. Gcse Help! Vermont neither requires nor offers a license to ati graphics carry a concealed handgun. [pic]Argument:

It is inconceivable that any logical person would believe that the answer to violence is more guns. Answer: One might have just as easily told Edward Jenner, the man who discovered in the late eighteenth century that the cowpox virus could be used to gcse inoculate people against smallpox, ‘It is inconceivable that any logical person would believe that the answer to solve a problem with disease is more viruses. Argument: The answer to physics coursework help bullets flying is not more bullets flying. Answer: Actually, the answer to bullets flying is graduate, almost always more bullets flying. That’s why the gcse coursework police bring so many guns with them when they respond to a report of ‘shots fired. Argument: The answer to school violence is prevention, not guns on campus. Install Thesis! Answer: Prevention and preparedness are not mutually exclusive. In a perfect system, the two approaches to safety compliment each other. Coursework Help! Preventive measures, such as teaching students and faculty to watch for solve ati graphics, the warning signs of mental illness and physics gcse help, providing counseling to disturbed students, can work hand in hand with preparative measures, such as developing campus alert systems, providing additional training to campus police, and allowing the same trained, licensed adults who legally carry concealed handguns when not on college campuses to do so on college campuses. Answer: Though statistically safer than other comparable locations, college campuses play host to every type of violence found in the rest of Proofreading & Editing society, from murder to assault to rape.

The statistics suggest that allowing concealed carry on campus won’t hurt and might help; therefore, there is physics coursework, no legitimate reason not to allow it. A free society does not deny the people a right unless there is empirical evidence that granting that right will do more harm than good. [pic]Argument: Some professors might be afraid to issue bad grades if they know that students could be carrying guns Answer: Why should professors be more afraid of issuing bad grades to students who want to carry guns LEGALLY than of issuing bad grades to students who might already be carrying guns ILLEGALLY? College campuses are open environments—they don’t have controlled points of derek bruening entry, metal detectors, or X-ray machines. In light of the fact that a person unconcerned with violating the rules can walk onto a college campus carrying pretty much anything he or she chooses, some professors might feel more comfortable about coursework help issuing bad grades if they knew they were allowed the cons means to defend themselves. Argument: The last thing we need is a bunch of vigilantes getting into a shootout with a madman, particularly since it’s been proven that trained police officers have an accuracy rate of only about 15-25% in the field Answer: Citizens with concealed handgun licenses are not vigilantes. Gcse Coursework! They carry their concealed handguns as a means of getting themselves out of harm’s way, not as an excuse to go chasing after bad guys.

Whereas police shooting statistics involve scenarios such as pursuits down dark alleys and armed standoffs with assailants barricaded inside buildings, most civilian shootings happen at pointblank range. In the Luby’s Cafeteria massacre, the wearing uniforms essay Columbine High School massacre, and the Virginia Tech massacre, the assailants moved slowly and methodically, shooting their victims from physics help, very close range. A person doesn’t have to be a deadeye shot to solve ati graphics driver defend himself or herself against an assailant standing only a few feet away(2). For these reasons and many others, firearms should be permitted on campus. The bottom line is that if the state allows someone to carry a firearm in public places, why should a college campus be any different? Virginia Tech massacre – Wikipedia, free encyclopedia 2. http://www.concealedcampus.org/common_arguments.php. Students for Concealed Carry on Campus – Supporting self-defense on Campus. Is this the perfect essay for physics gcse coursework, you? Save time and order Firearms on pros cons wearing uniforms College Campus. essay editing for only $13.9 per page.

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