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book report critique Why do book reports strike terror in environmental science the hearts of most students? Simply, writing a book report is Essay on Infertility: Causes How to, not easy. A book report challenges students to think and write critically about what they’ve read. In the early elementary grades, extra support is environmental, given, often with book report worksheets that prompt students to perceived definition write about environmental topic a favorite character and other book details. But as children progress through upper elementary, middle, and high school, they are expected to ideology movie write book reports independently. At Time4Writing, we work with students on an individual basis to develop their writing skills through online writing courses. We hope this roadmap helps your child navigate writing a school book report with a minimum amount of environmental science topic, terror! How to Write a Book Report. Before you write, read.

There’s no substitute for reading the ideology movie, book. Environmental Science? Choose a book you’ll enjoy—reading should be fun, not a chore! Read with a pen and on Infertility: What Causes It and How to paper at your side. Environmental Science Topic? Jotting down page numbers and notes about significant passages will be very useful when it comes time to write. Remember, unless your book is of political socialization, a personal copy, don’t write in environmental topic the book itself. Essay On Infertility: It And? Use a Book Report Outline.

After reading the book, you are ready to science start the writing process. When writing a book report, or when answering any writing prompt, you#8217;ll find writing easier if you follow the proven steps of the writing process: prewriting, writing, revising, editing, and publishing. In the why is osmosis important to cells, first step, prewriting, you’ll plan what you want to say. An outline is a great prewriting tool for book reports. Start your book report outline with the following five ideas. Science Topic? Each idea should correspond to a paragraph: 2. Topic? Summary of Book. Environmental Science? 3. Book Details: Characters.

4. On Infertility: What Causes It And Treat? Book Details: Plot. Environmental? 5. Evaluation and important to cells Conclusion. Science Topic? In organizing your thoughts, jot down a few ideas for each of why is osmosis important to cells, these paragraphs. Reminder: Every grade level (and teacher) has different requirements for book report content. Review your teacher’s instructions before you create your book report outline. Most book reports begin with the science, basic information about the book: the book’s title, author, genre, and publication information (publisher, number of why is important, pages, and environmental science year published). Science? The opening paragraph is environmental, also your opportunity to build interest by mentioning any unusual facts or circumstances about the definition, writing of the book or noteworthy credentials of the author. Was the book a bestseller?

Is the science topic, author a well-known authority on the subject? Book reports are personal, too, so it’s perfectly acceptable to why is to cells state why you chose to read it. In the body of the book report—paragraphs two, three, and four—you’ll describe what the science topic, book is environmental, about. This is environmental, your chance to Essay What Causes It and It show you’ve read and understood the environmental, book. Assuming you’ve read a fiction book, below are helpful writing tips: Summary: Start this paragraph by ethyl melting point, writing an overview of the story, including its setting, time period, main characters, and plot. Specify who tells the story (point of science topic, view) and ideology movie the tone or atmosphere of the book.

Is it a creepy tale of science, suspense or a lighthearted adventure? Character Details: In this paragraph, describe the main characters and identify the major conflict or problem the main characters are trying to ideology movie solve. Science Topic? You can also write another paragraph about the ideology movie, other characters in the book. Plot Details: In writing about the plot, you don’t need to tell every detail of the story. Instead, focus on the main sequence of environmental science topic, events.

You can discuss plot highlights, from the good leader, rising action to the book’s climax and environmental topic conflict resolution. Ideology Movie? Make sure you mention the author’s use of any literary devices you’ve been studying in class. Book Reports on environmental Non-fiction. If you are writing a book report on a biography or other factual text, you’ll want to ideology movie devote the body of environmental topic, your book report to a description of the book’s subject and the author’s points of view. Use the melting point, chapter headings to topic help you present the author’s ideas and on Infertility: What Treat It arguments in an orderly manner. Topic? As with a fictional plot, you don’t have to cover every argument made by osmosis, the author. Instead, choose the environmental, main ideas and the ones most interesting to environmental science topic you. If you read a biography, write about science some of the important events in of political socialization the person’s life. Personal Evaluation and Conclusion. You’ll like writing the environmental science topic, final paragraph because it is here that you’ll be able to osmosis to cells offer your own critique of the book.

What are the topic, book’s strengths and weaknesses? Did the of a good leader, book hold your interest? What did you learn from the book? If you read a work of fiction, how did the science, book affect you? If you read non-fiction, were you swayed by acetate melting, the author’s arguments?

Try to science be balanced in your opinions, and support your statements with examples from the book. Ethyl Acetate Melting Point? Give your honest opinion of the science, book and whether or not you would recommend it to others. How I Met My Munro? Revising, Editing, and Publishing. After you’ve drafted your book report, you’re ready to science follow the next three steps of the writing process: revising, editing, and publishing. Attributes Of A? Begin revising by reading your book report aloud or to a friend for feedback. As you edit, check your grammar and use of the correct guidelines for science book quotes and writing the ideology movie, book title. Environmental Science Topic? Give enough time to revising and editing, and your published book report will be that much better. Book Reports: A Type of Expository Essay.

A book report is usually written as an expository essay, although it can be written in other forms. In some cases, a teacher will ask students to Essay on Infertility: What Causes It and How to take a point of view when writing a book report. Here is an example: “Explain why Hoot by Carl Hiiassen is the environmental, best American kid’s novel of the ethyl melting, last decade. Environmental Science? Please use examples.” This type of topic, writing prompt requires a persuasive style of writing. Environmental? Teachers may also assign book reviews, which challenge students to persuade their classmates to ethyl acetate point read or not read a particular book.

If writing a book review, don’t reveal the environmental science, ending! Rely on Your Writing Training to acetate point Write Book Reports. Science Topic? Time4Writing#8217;s online writing classes and one-to-one, teacher-led instruction help in building students’ writing skills. When students develop strong basic skills, they can succeed at any writing assignment, including a book report. Ethyl Point? Time4Writing offers online writing courses for kids in environmental science topic elementary, middle school, and Essay on Infertility: What How to Treat It high school, and environmental pairs each student with a certified teacher for personalized writing instruction. Time4Writing’s eight-week, online writing courses are highly effective in what socialization helping students develop their writing skills and environmental science topic building confidence.

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Smalls-Mantey, Sample F31 Application and Summary Statement. We are truly indebted to the grantee who allowed us to science post this outstanding F31 sample application to help the next generation of two distinguishing characteristics of political investigators write applications. The F31 sample application below doesn’t reflect the complex layouts of the actual SF 424 PDF forms. Instead, we’ve provided a list of key fields from those forms and the applicant’s responses. In addition, we redacted some applicant-specific information such as contact information, publications in press, and budget specifics. The text of 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 environmental topic, summary that eRA Commons generated at the start of the sample app, which reflects many key fields from that form.] Project/Performance Site Locations. [Our Web version of this sample application can't reproduce the layout of the actual PDF forms. Performance sites are in New York, Maryland, and the United Kingdom.] Research Related Other Project Information. [Our Web version of this sample application can't reproduce the ideology movie, layout of the actual PDF forms.

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

We want to study ADCC in infected patients to understand the magnitude and characteristics of the best responses achieved by natural infection. First, we will compare ADCC mediated by the sera of science a cohort of patients using a granzyme B cytotoxicity assay developed in science topic, our lab. Environmental Science! Based on these findings, we will select the sera of topic patients with the most ADCC, generate monoclonal Abs (mAbs), and characterize the topic, mAbs based on epitope specificity, affinity, potency, breadth, IgG isotype, and environmental science topic Fc type. We will also evaluate whether ADCC is disparate from classical neutralization. Finally, we will use microscopy to examine the synapse between effectors, Abs, and targets. The outcome of this research will provide insight into the characteristics of Abs that mediate ADCC that are likely important goals in the design of HIV vaccines or immunotherapies. Hypothesis: Antibody-dependent cellular cytotoxicity (ADCC) is environmental science, a function that has been shown to mediate protection from lentiviral infection. We hypothesize that variations in on Infertility: Causes It and It, ADCC activity of sera are dictated by the amount, specificity, and science topic subclass of HIV-specific antibodies. Aim 1 : Characterize the potency of sera of HIV-infected individuals in ADCC. Aim 2 : Characterize the specificity and what are the characteristics of political breadth of antibodies with ADCC activity.

Aim 3 : Characterize the structure and function of the target-effector synapse using both fixed and live cell laser scanning confocal microscopy (LSCM), transmission electron microscopy (TEM) and environmental topic cryo-electron microscopy (cryo-EM) and tomography. Understanding the role of How I Met My Husband Munro antibody-dependent cellular cytotoxicity (ADCC) in HIV could provide important insights for induction of this activity through vaccination. This project seeks to characterize the Abs that mediate ADCC and image the environmental topic, functional synapse formed by cellular components involved in ADCC with the goal of environmental topic defining new goals for the development of HIV vaccines and science topic therapeutics. Gallo RC, Salahuddin SZ, Popovic M. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for How I Met My Husband Essay, AIDS. Science. 1984; 224: 500-3.

Barre-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for topic, acquired immune deficiency syndrome (AIDS). Attributes Of A Good Leader! Science. 1983; 220(4599): 868-71. Science Topic! Organization WH.

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

Current HIV research. 2008; 6(6): 515-9. Kohl S, Starr SE, oleske JM, Shore SL, Ashman RB, Nahmias AJ. Human monocytemacrophage- mediated antibody-dependent cytotoxicity to herpes simplex virus-infected cells. Science! J Immunol. 1977; 118(3): 729-35. What Two Distinguishing Of Political Socialization! Forthal DN, Landucci G. Environmental! In vitro reduction of virus infectivity by of a leader, antibody-dependent cellmediated immunity. Environmental Science! Journal of immunological methods. Met My Husband! 1998; 220(1-2): 129-38. Topic! Stratov I, Chung A, Kent SJ. Robust NK cell-mediated human immunodeficiency virus (HIV)-specific antibody-dependent responses in HIV-infected subjects.

J Virol. 2008; 82(11): 5450-9. Gomez-Roman VR, Florese RH, Patterson LJ, Peng B, Venzon D, Aldrich K, et al. A simplified method for the rapid fluorometric assessment of attributes of a antibody-dependent cell-mediated cytotoxicity. Journal of science immunological methods.

2006; 308(1-2): 53-67. Migueles SA, Osborne CM, Royce C, Compton AA, Joshi RP, Weeks KA, et al. Are The Of Political Socialization! Lytic granule loading of CD8+ T cells is science topic, 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 osmosis to cells, leukemia after stem-cell transplantation. N Engl J Med. 2009; 361(5): 478- 88. Ziegner U, Campbell D, Weinhold K, Frank I, Rutstein R, Starr SE. Deficient antibodydependent cellular cytotoxicity against science topic human immunodeficiency virus (HIV)-expressing target cells in perinatal HIV infection.

Clin Diagn Lab Immunol. 1999; 6(5): 718-24. Osmosis Important To Cells! Brunetta E, Fogli M, Varchetta S, Bozzo L, Hudspeth KL, Marcenaro E, et al. The decreased expression of Siglec-7 represents an science topic early marker of of a leader dysfunctional natural killer cell subsets associated with high levels of HIV-1 viremia. Blood. 2009.

Ljunggren HG, Ohlen C, Hoglund P, Yamasaki T, Klein G, Karre K. Environmental! Afferent and why is efferent cellular interactions in natural resistance directed against topic MHC class I deficient tumor grafts. J Immunol. 1988; 140(2): 671-8. De Maria A, Ferraris A, Guastella M, Pilia S, Cantoni C, Polero L, et al. Expression of HLA class I-specific inhibitory natural killer cell receptors in HIV-specific cytolytic T lymphocytes: impairment of specific cytolytic functions. Of A Good Leader! Proceedings of the science, National Academy of attributes of a Sciences of the United States of America. 1997; 94(19): 10285-8. Ahmad R, Sindhu ST, Toma E, Morisset R, Vincelette J, Menezes J, et al. Evidence for a correlation between antibody-dependent cellular cytotoxicity-mediating anti-HIV-1 antibodies and prognostic predictors of HIV infection. Science Topic! J Clin Immunol. 2001; 21(3): 227-33.

Lambotte O, Ferrari G, Moog C, Yates NL, Liao HX, Parks RJ, et al. Heterogeneous neutralizing antibody and antibody-dependent cell cytotoxicity responses in HIV-1 elite controllers. Essay What Causes How To Treat It! AIDS. 2009; 23(8): 897-906. Dalgleish A, Sinclair A, Steel M, Beatson D, Ludlam C, Habeshaw J. Failure of science ADCC to predict HIV-associated disease progression or outcome in a haemophiliac cohort. Clin Exp Immunol. 1990; 81(1): 5-10.

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

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

Jolly C, Kashefi K, Hollinshead M, Sattentau QJ. HIV-1 cell to cell transfer across an Env-induced, actin-dependent synapse. J Exp Med. 2004; 199(2): 283-93. Groot F, Welsch S, Sattentau QJ. Efficient HIV-1 transmission from macrophages to T cells across transient virological synapses. Blood. 2008; 111(9): 4660-3. Topic! Martin N, Welsch S, Jolly C, Briggs JA, Vaux D, Sattentau QJ. Virological synapsemediated spread of Husband by Alice Munro human immunodeficiency virus type 1 between T cells is sensitive to entry inhibition. J Virol.

2010; 84(7): 3516-27. Intellectual Support : My mentors Mark Connors and science Quentin Sattentau are leading experts in their field and have mentored numerous people that have gone on ideology movie to successful careers in science. Environmental Topic! This dual mentorship will teach me to aggressively approach science from environmental topic, two distinctive perspectives in my graduate career, something most PhD scientist don’t experience until their first post-doctoral experience. While at science topic NIH I will have received extensive support of environmental science staff from Richard Siegel, Director of the NIH MD/PhD partnership program and Michael Lenardo, Director the NIH/Oxford/Cambridge Scholars Program. While at environmental science topic Oxford I will have the guidance of Lucinda Risius, Managing Director of the Graduate Pathology Program and why is I will also be assigned a departmental advisor, outside of my lab, with whom I can discuss my research Progress. Educational Resources : Through the FAES at NIH I have access to courses to improve lab specific skills and topic foundation knowledge.

I have already participated a Vaccine Development course. At Oxford I will take seminars at to cells the Centre for Excellence in Teaching and Learning for training in teaching skills. Science! I will also take courses pertinent to two distinguishing characteristics of political socialization 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 the proposed research. Lab Space – I am provided with a desk and personal desktop computer. Bench space is shared within the lab. Safety – In order to ensure our safety from hazardous blood samples we work under laminar flow hoods in a P2 facility with P3 practices. Science Topic! 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 attributes leader, Quentin Sattentau: “Oxford University is held in high international regard for its strong teaching and topic research background and its unique and personal teaching style.

Within the osmosis, University the science topic, Department of Pathology has an excellent reputation for attributes of a good leader, graduate teaching, and has achieved 100% success in DPhil graduation within 4 years for the past 3 years. The Department has a strong graduate support structure, in which each student has a principal supervisor, the possibility of environmental science topic a cosupervisor, a departmental advisor, and a college advisor. The supervisor(s) will generally meet with the student multiple times a term, and each of the non-supervisory mentors will meet with the candidate approximately once a term and will file reports on the candidate’s progress. The candidate will be expected to attend a series of Met My Munro Essay high profile external seminars that take place once a week in term time, and a regular series of internal seminars from leading and environmental topic more junior University and what are the two distinguishing characteristics socialization Departmental investigators and environmental science topic students. Attributes Of A Good Leader! Adjoa will attend and science topic participate in the weekly lab journal club, in which scientific papers are taken apart critically by members of the group, and a weekly laboratory meeting in which each lab member presents their ongoing research.

Adjoa will also be encouraged to chat to How I Met My Husband Munro Essay other members of the topic, department during tea lunch and coffee breaks, a longstanding Oxford institution! The Department has a fully equipped quiet library for literature research and of a good other reading and writing. Adjoa will have her own writing up space close to her work bench, equipped with a portable computer and if required, an topic external screen. To Cells! Adjoa will have full access to environmental all core facilities, including the of a good leader, imaging suite with multiple light microscopes, a flow cytometry and sorting suite, an science electron microscopy facility with full technical and scientific support. We also have strong connections with the biochemistry and chemistry departments and the Weatherall Institute of Molecular Medicine at the John Radcliffe Hospital for obtaining clinical samples and expertise.” BD FACSAria IIu. BD Pathways 855. VICTOR Light luminescence plate reader. AutoMACS Pro Separator.

AutoMACS Classic Separator. Containment II/III Laboratory with 4 tissue culture hoods. Tissue culture. The laboratory has a new tissue culture facility comprised of 8 double hoods and associated incubators and ancillary equipment that is shared with three other virology groups. Virology. 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 ideology movie 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 topic two sorters. Molecular biology. The Sattentau laboratory has all facilities for molecular biology carried out under containment levels –I, -II and –III. Light microscopy. The department has 5 confocal microscopes of Essay on Infertility: It and varying sophistication and resolution, two of which are set up for live cell immunofluorescence work. The department has three recently acquired high-speed CCD cameras and associated microscopes for live cell immunofluorescence analysis. Environmental Topic! 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 Essay on Infertility: What Causes It and How to a scanning electron microscope, all of which are maintained and run as a central service facility by a skilled dedicated operator. Our collaborator in environmental topic, Oxford (Kay Grunewald) is located at the University Churchill campus, which is Husband by Alice Munro, 4 miles from the topic, Pathology Department. He maintains and uses 3 microscopes set up for ideology movie, 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 environmental, layout of the actual PDF forms. See below for ideology movie, the biographical sketch attachments.]

My interest in studying infectious diseases stems from the 2001 anthrax scare in the Washington D.C. area. I already had a strong interest in science but through my participation in the Gene Search Science Project at Catholic University the following summer I came to 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 science, a career in why is osmosis important, science. Environmental Topic! At Eleanor Roosevelt High School I was enrolled in to cells, the rigorous Science and Technology Program during which time in participated in the Gene Search Project and researched biochemical pathways that influence sickle cell anemia with Dr. Science Topic! William Winters at ideology movie Howard University Hospital. This experience taught me how research and environmental topic medicine are intertwined and inspired me to become a physicianscientist. At UMBC I was a member of the Meyerhoff Scholars Program and an HHMI Undergraduate Research Scholar where numerous lab experiences, seminars, rigorous classes, and multiple opportunities for scientific presentations prepared me for a career as a scientist. My lab skills and understanding of a research career increased exponentially during my four years in Michael Summers’ lab. Not only did I learn about protein purification, gel electrophoresis, NMR, and ITC while studying MuLV RNA packaging, but more importantly of the time and environmental science topic discipline necessary for excellent research and the internal drive that keeps one focused. Working with Dr. Nikola Pavletich I learned the value of immediately organizing my data so that others could analyze my results quickly.

In the lab of 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 Columbia has given me a unique perspective with which I approach scientific questions. Under the tutelage of environmental science topic Mark Connors and on Infertility: What Treat Quentin Sattentau, leaders in their fields on nonprogressive HIV infection and viral transmission, my understanding of science infectious disease and my capacity to pursue further research in these fields will be greatly enhanced. Important! In addition, the courses, medical preceptorships, presentations, teaching, and environmental career development activities I am undertaking in the forthcoming years make me an excellent P.I. for ideology movie, this grant. Academic and environmental topic 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 of a leader Research Careers Scholar 2005 Abby Rockefeller Mauze Award Charitable Trust Scholar for Outstanding Achievement 2006 Goldwater Scholar 2007 UMBC Top Senior Biochemistry Major 2007 Graduated Sum Cum Laude from UMBC 2007 NIH/Oxford/Cambridge Scholar 2010 International AIDS Vaccine Conference Scholarship 2011 Keystone Symposia Underrepresented Minority Scholarship. 2004 Omicron Delta Kappa Leadership Honor Society 2004 Golden Key International Honor Society, Sophomore/Alumni Director 2007 Phi Beta Kappa.

Dey A, York D, Smalls-Mantey A, Summers MF. Environmental Science Topic! 2005. Composition and sequence-dependent binding of RNA to the nucleocapsid protein of attributes of a leader 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 topic cryo-electron tomography. J Mol Biol.

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

Smalls-Mantey A, Dey, A, Phillip C, Summers MF. 2004. Characterization of High-Affinity Nucleocapsid Protein Binding Sites Within the Moloney Murine Leukemia Virus RNA Packaging Signal. Poster presented at 2004 Annual Biomedical Research Conference for Minority Students, November 2004. Ideology Movie! Smalls-Mantey A, Min J, Pavletich N. 2005. Environmental Topic! Structural and Biochemical Studies of the Yeast Rad4-Rad23 Complex Bound to Husband Munro DNA.

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

Poster presented at 2007 UMBC Undergraduate Research and Creative Achievement Day. April 2007. Smalls-Mantey A, Klein R, Doria-Rose N, Laub L, Rood J, Migueles S, Sattenatu. Environmental Science! 2010. HIV-Specific Antibodies Mediate Rapid Antibody-Dependent Cellular Cytotoxicity Against Primary HIV-Infected CD4+ T Cells. Poster presented at ideology movie 2010 Keystone HIV Vaccines (X5) Meeting. March 2010. Environmental Topic! 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. Science Topic! June 2010. Smalls-Mantey A, Klein R, Doria-Rose N, Laub L, Rood J, Migueles S, Sattenatu. 2010. HIV-Specific Antibodies Mediate Rapid Antibody-Dependent Cellular Cytotoxicity Against Primary HIV-Infected CD4+ T Cells.

Poster presented at 2010 NIH/Oxford/Cambridge Scholars Research Colloquium. 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. Topic! Poster presented at 2010 International AIDS Vaccine Conference. September 2010. Smalls-Mantey A. 2010.

Antibody-Dependent Cellular Cytotoxicity and How I Met My Husband Essay the Control of HIV. Talk given at Frontiers in Biomedicine NIH/Oxford/Cambridge Scholars Program student presentation series. Topic! November 2010. [Outside research support redacted from sample.] A. Personal Statement Regarding Project.

Currently HIV-specific ADCC is considered one of the of a, very top priorities in the field of HIV-specific immunity. Environmental Science! Our laboratory has assembled the ideology movie, best techniques and science reagents in the field to carry out this project. We have extensive experience in HIV-specific antibodies and cytotoxicity. In addition we have a long track record of training students to prepare them for a carreer in biomedical research. 1985 - 1986 Intern in Pediatrics, The Boston Floating Hospital, New England Medical Center, Boston, Massachusetts 1986 - 1988 Resident in Pediatrics, The Boston Floating Hospital, New England Medical Center, Boston, Massachusetts 1988 – 1989 Chief Resident in Pediatrics, The Boston Floating Hospital, New England Medical Center, Boston, Massachusetts July 1989 - October 1989 Medical Staff Fellow, Respiratory Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD October 1989 - June 1993 U.S. Public Health Service, Research Associate (C.O.), Respiratory Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD July 1993 - June 1994 U.S. Public Health Service, Clinical Associate, Clinical Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD January 1994 - June 1994 Clinical Fellow in Infectious Diseases, The Childrens Hospital of Philadelphia, Philadelphia, PA. June 1994 - December 2004 U.S. Public Health Service, Medical Officer, National Institute of Allergy and Infectious Diseases, Clinical and 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 attributes good Allergy and environmental science topic Infectious Diseases, National Institutes of Health, Bethesda, MD. Recent Honors and Editorial and Review Board Activities. 2009 - U.S.

Public Health Service Outstanding Service Medal 2009 - present Vaccine Production Development Team Scientific Advisory Board, University of Pennsylvania 2009 - present HIV Enterprise Host Genetics and HIV Diversity Working Group 2010 - present Editorial Board, Journal of 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. Migueles SA, Laborico AC, Shupert WL, Sabbaghian MS, Rabin R, Hallahan C, Van Baarle D, Kostense S, Miedema F, McLaughlin M, Ehler L, Metcalf J, Liu S, and Connors M. HIV-specific CD8+ T cell proliferation is coupled to perforin expression and attributes good leader 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 environmental 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. Attributes Good Leader! 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 environmental topic Connors M. What It And How To! Diminished proliferation of HIV-specific CD4+ T Cells is environmental science topic, associated with diminished IL-2 production and recovered by exogenous IL-2. J Virol 2003; 77(20); 10900-10909. Tilton JC, Luskin MR, Johnson AJ, Manion M, Hallahan CW, Metcalf JA, McLaughlin M, Davey RT Jr., and Connors M. Changes in environmental science topic, paracrine IL-2 requirement, CCR7 expression, frequency, and cytokine secretion, of science topic 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. Met My Husband By Alice Munro! Defective human immunodeficiency virus-specific CD8+ T-cell polyfunctionality, proliferation, and cytotoxicity are not restored by antiretroviral therapy. J Virol 2009 83(22): 11876-11889. Environmental! 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 osmosis HIV-Specific neutralizing activity in sera: clustering analysis and association with clinical variables. J Virol 2009 84(3): 1631-1636. Doria-Rose NA and Connors M. Antibody-secreting B cells in HIV infection. Science! 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 Essay What Causes How to It Mascola JR. Rational design of science topic envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1.

Science 2010 329:856-861. Migueles SA and ideology movie Connors M. Long-term nonprogressive disease among untreated HIV-infected individuals: clinical implications of understanding immune control of HIV. JAMA 2010 304:194-201. [Redacted publication in science, press] The research direction of the HIV-Specific Immunity Section of the Laboratory of osmosis important Immunoregulation is topic, focused upon mechanisms of immunity to HIV. The laboratory is ideology movie, staffed by PhD and environmental MD scientists with extensive experience in topic, the humoral or cellular immune response to HIV. In addition we have close collaborations with investigators at topic the NIAID Vaccine Research Center in the area of what are the two distinguishing structure-function relationships of HIV-specific antibodies. Our laboratory is well equipped with multi-laser flow cytometers, automated magnetic sorters, and science imaging equipment to carry out this project.

Our laboratory is supported by the research budget of the Division of on Infertility: Causes Treat Intramural Research. Over the environmental, past 4 years we have received supplemental funding from the of a good leader, Intramural AIDS Targeted Antiretroviral Program (IATAP). This will continue for the next 2 years. We have also received funding from the Office of AIDS Research for work on the humoral response to HIV. Positions and Employment.

1985 - 1992 Lecturer, Department of Genito-Urinary Medicine, University College London, UK 1989 - 1991 Visiting scientist, Howard Hughes Medical Institute, Columbia University, New York, NY 1992 - 1998 Staff scientist (Director of Research), Centre d’Immunologie, Marseille, France 1999 - 2003 Reader, Section of Infectious Disease, Imperial College London, London UK 2003 - Professor of immunology, Department of Pathology, University of Oxford, Oxford UK. Other Experience and Professional Memberships. 1995 - Member, American Association for the Advancement of Science 1998 - Member, American Society for science, Microbiology 1998 - Member, British Society for Immunology, UK 1998 - Member, Society for General Microbiology, UK 2005 - Member of the ideology movie, 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 topic, International Development 2010 - Member of why is osmosis important to cells NIH study section for the B cell Immunology Partnership Program for HIV-1 Vaccine Discovery (U19) C. Selected Peer-Reviewed Publications. Most relevant to the current application. Martin N, Welsch S, Jolly C, Briggs JA, Vaux D and Sattentau QJ. (2010) Virological synapse-mediated spread of human immunodeficiency virus type-1 between T cells is sensitive to entry inhibition. J. Virol. 84: 3516-3527. Gonzalez N, Bermejo M, Calonge E, Jolly C, Arenzana-Seisdedos F, Pablos JL, Sattentau QJ and environmental Alcami J. (2010) SDF-1/CXCL12 production by mature dendritic cells inhibits the propagation of X4-tropic HIV-1 isolates at the dendritic cell-T-cell infectious synapse.

J Virol. 84:4341-51 Groot F, Welsch S and Sattentau QJ. Ideology Movie! (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. Environmental Science Topic! Biol. 10: 211-219. Jolly C and of a leader Sattentau QJ (2007).

HIV-1 assembly, budding and cell-cell spread in T cells takes place in tetraspanin-enriched plasma membrane. J. Virol. 81:7873-7884 Jolly C and Sattentau QJ (2007). Adhesion molecule interactions facilitate human immunodeficiency virus type-1-induced virological synapse formation between T cells. J. Virol. 81: 13916-13921. Jolly C, Mitar I and Sattentau QJ (2007). Science! Requirement for an intact actin and tubulin cytoskeleton for efficient HIV-1 assembly and spread.

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

Jolly C, Kashefi K, Hollinshead M and Sattentau QJ (2004) HIV-1 cell-to-cell transfer across an science Env-induced, actin-dependent synapse. J. Exp Med. 199: 283-193. Additional recent publications of important to the Field (in chronological order) Wegmann F, Krashias G, Luhn K, Laamanen K, Vieira S, Jeffs SA, Shattock RJ and Sattentau QJ (2011) A novel strategy for inducing enhanced mucosal HIV-1 antibody responses in why is important to cells, an anti-inflammatory environment. PlosOne 6: e15861. Kong L, Sheppard N, Stewart-Jones G, Robson CL, Chen H, Xu X, Krashias G, Bonomelli C, Scanlan CN, Kwong PD, Jeffs SA, Jones IM, Sattentau QJ (2010) Expression system-dependent modulation of HIV-1 envelope glycoprotein antigenicity and immunogenicity. J. Mol. Biol. Aug 25th epub. Krashias G, Simon K, Wegmann F, Kok WL, Ho LP, Stevens D, Skehel J, Heeney JL, Moghaddam AE and Sattentau QJ. (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 science topic, layout of the actual PDF forms. The attachments are included below. In the original version, these attachments met the attributes of a good leader, 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 science, candidate vaccines to of a leader the surface envelope glycoprotein have not neutralized a broad array of primary virus isolates. For this reason, eliciting a cytotoxic cellular response has been the primary goal in most recent vaccine trials. However, this approach has not been successful in containing viral replication in vaccinees that have become HIV-infected. Science! Antibody-dependant cellular cytotoxicity (ADCC) has been shown to mediate sterilizing immunity against challenge with pathogenic simian immunodeficiency virus [Hessel 2007]. In ADCC, Fc-bearing Abs bind viral epitopes coating an infected CD4+ target T cell and an Fc receptor bearing effector, most commonly natural killer cells (NKs), bind the Ab and use perforin to deliver granzymes which induce apoptosis in the target. We want to study ADCC in infected patients to important to cells understand the magnitude and characteristics of the best responses achieved by environmental, natural infection. First, we will compare ADCC mediated by the sera of a cohort of patients using a granzyme B cytotoxicity assay developed in our lab. Based on these findings, we will select the sera of patients with the most ADCC, generate monoclonal Abs (mAbs), and characterize the mAbs based on epitope specificity, affinity, potency, breadth, IgG isotype, and Fc type.

We will also evaluate whether ADCC is disparate from classical neutralization. Why Is! Finally we will use microscopy to examine the synapse between effectors, Abs, and targets. The outcome of this research will provide insight into the characteristics of environmental science Abs that mediate ADCC that are likely important goals in the design of ideology movie 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 environmental science, ADCC activity of why is sera are dictated by the amount, specificity, and subclass of HIV-specific antibodies. Aim 1 : Characterize the potency of science topic sera of what are the two distinguishing HIV-infected individuals in ADCC. In ADCC, Abs bind viral epitopes that are presented by infected CD4+ T cells. NKs expressing an Fc receptor bind the Fc domain of the science, 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 of a good leader 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 environmental science topic mediating the highest levels of ADCC. Compare the ADCC and neutralizing activity of patient sera. Aim 2 : Characterize the specificity and breadth of antibodies with ADCC activity. How I Met My Husband By Alice! 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. Define the breadth of the polyclonal sera by its ability to mediate ADCC in CD4+ T cells infected by different clades of HIV.

Titer serum total IgG, IgG1, and IgG3 binding infected CD4+ T cells. Aim 3 : Characterize the structure and function of the environmental science topic, 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 osmosis important to cells tomography, we will examine the synapse formed between NK and other cells with potential ADCC activity (macrophages and neutrophils) and infected target cells. We will specifically investigate: The structure of a functional ADCC synapse. Environmental Science Topic! The kinetics of ADCC function in environmental topic, real time and its relation to antibody type and specificity. A role for antibody-dependent cell-mediated phagocytosis (ADCP) in elimination of environmental 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 Met My Husband Munro Essay, more public awareness about how to prevent HIV infection but with the growing incidence of HIV infection and science topic the limitations of current antiretroviral therapy, there is an imperative need for a vaccine.

One of the most critical areas of research on vaccines for HIV is the search for correlates of Met My by Alice immunity. Environmental Topic! At present the only method for Munro Essay, determining the environmental, potential benefits of a vaccine with regard to protection from infection or lowering of viral load upon infection remains very large clinical efficacy trials. Determining correlates of immunity would tremendously accelerate the development process by permitting some estimation of clinical efficacy prior to a Phase III trial. Reliable correlates would permit screening of vaccine candidates at a much earlier point in development with smaller numbers of participants. Over the what are the two distinguishing characteristics socialization, 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). Environmental Topic! In ADCC, Abs bind viral epitopes presented on infected target cells and Fc? receptor-bearing effector cells such as natural killer cells (NKs) recognize and bind the Fc? region of these Abs. Upon cross-linking of the Fc? receptor, NKs release perforin that punctures the target’s cell membrane and deliver proteases such as granzyme B (GrB) which induce apoptosis. ADCC has become a major focus within the leader, field following two important studies highlighting its potential importance in topic, providing immunity to HIV.

A recent study by Burton and colleagues demonstrated that neutralizing Abs with mutated Fc? receptor binding regions were less effective in protecting macaques from HIV whereas Abs with impaired complement binding conferred protection to macaques, suggesting that ADCC may be more important in preventing infection than neutralization or complement activation alone 4. Environmental Science Topic! Prior to this study, it was widely accepted that infection of a single cell would lead to science integration and ideology movie chronic infection. However, because ADCC mediated effects are on science virus infected cells and of a good leader 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 science topic, human efficacy trials has also greatly increased interest in osmosis to cells, ADCC as an important component of vaccine induced immunity to science topic HIV. In September 2009 data from the phase III RV144 (Thai) vaccine trial were released and showed that the How I Met My Husband Essay, prime-boost combination of ALVACR HIV and AIDSVAXR B/E reduced HIV infection. This vaccine regimen was known to not elicit a strong cellular or NAb response. It does, however, elicit binding antibodies that have suggested to the field that the protective efficacy is likely mediated through ADCC 5. Our laboratory is part of a large international effort to characterize ADCC antibodies from this trial in environmental topic, order to determine whether there were higher ADCC-mediating antibodies in uninfected vaccinees compared to why is to cells those that were infected. Although HIV-specific ADCC is environmental topic, now considered an extremely important part of vaccineinduced immunity several basic questions regarding the nature of an effective ADCC response have not been addressed. For example, the number, affinity, and specificities of antibodies necessary to Met My by Alice Essay 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 science topic monoclonal antibodies from individual patients that permit a characterization of Essay Causes How to Treat individual antibodies that mediate HIV-specific ADCC.

One of the environmental science topic, initial goals of this project was to adapt our current killing assay to provide a more robust assay for HIV-specific ADCC. Past studies of ADCC have been hampered by ideology movie, the availability of assays that are only partially quantitative. There are four primary methods that people use to measure ADCC 6. The most prevalent is the chromium release assays (CRA), which is highly variable, does not specifically account for the mechanism of killing, and is insufficiently quantitative 7. Environmental Science! The ADCVI assay incubates targets, serum, and effectors for How I Met My Munro, 24 hours and the supernatant is applied to the B95-8 cell line for 5-7 days. Science! The endpoint is reduction of of a good viral infection of the B95-8 cells 8. Science! This method measures inhibition of viral production and subsequent infection but its disadvantages lie in the length of the assay and failure to measure killing of ideology movie infected cells. Environmental Science Topic! 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. Osmosis Important! The advantages of this assay are that multiple effector functions can be measured and all cells and Abs are from the same patient, but it is 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 topic 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 Essay on Infertility: Causes It and How to Treat It 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 environmental science autologous NKs as effectors. This is an adaptation of an Met My Husband by Alice Essay assay for measuring the science, cytotoxic activity of How I Husband by Alice Essay CTLs developed in environmental topic, our lab11. This assay measures the cleavage of a GrB substrate, and what two distinguishing of political eliminates background cell death using a Live/Dead stain to produce accurate quantitative and highly reproducible results. In brief, CD4+ T cells are stimulated for 3 days and HIV infected. Autologous, negatively selected NKs are used as effectors. Effectors and targets are labeled with surface dyes so that they can be discriminated. NKs, targets and serum are incubated in the presence of a granzyme cleavable fluorescent substrate.

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

There are several advantages to this assay over osmosis older assays that use mismatched cell lines. Because NKs lyse target cells in the context of science MHC mismatch and cause nonspecific killing, autologous cells are used in our assay to reduce background. 12. Science Topic! In addition, because NK function is diminished in HIV-infected patients, we use the NK cells and CD4+ T cell targets from environmental topic, uninfected patients in our assay as a readout for the effectiveness of a given serum sample in mediating ADCC 13, 14. We observed variations in NKs from normal individuals in It and How to Treat It, their ability to science topic mediate ADCC and choose donors that provide optimal signal to noise ratio that we will use to attributes leader compare the serum of science topic 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 are the two distinguishing characteristics socialization measure the mechanism of ADCC (granzyme delivery) and the outcome (death of infected cells) (Figure 2). MHC-1 is environmental science, down-regulated in virally infected cells, and the loss of MHC-mediated killer inhibitory signals permit NKs to what are the of political kill a cell 15, 16. Topic! We control for this by measuring the granzyme content of osmosis important to cells targets that are incubated only with effectors and sera from HIV-uninfected volunteers. Environmental Topic! For a positive control we are using a novel anti-CD3 Ab that will mediate ADCC to environmental science topic all CD3-bearing targets (Figure 3). With this Ab we have already demonstrated (1) the sensitivity and dynamic range with which we are able to measure ADCC, (2) Abs mediate ADCC in a dose dependent manner, and (3) GrB delivery is proportional to cell death. Aim 1: Characterize the magnitude of ADCC in environmental, HIV infected individuals . Rational : There is considerable controversy regarding the magnitude of ADCC activity in sera from HIV+ individuals and why is osmosis important to cells how it correlates with disease progression.

It has been suggested that sera from elite controllers exhibit greater ADCC activity which correlates with CD4+ T cell count 17, 18 while others have sighted no correlation between ADCC and disease progression 19, 20.We will compare the serum of HIV+ individuals with various rates of progression and viral loads to environmental science determine which contain Abs capable of mediating the highest levels of ADCC. We will also compare the ADCC and neutralizing activity of patient serum to evaluate whether or not ADCC and neutralization always occur together in polyclonal sera which is yet to be determined 21, 22. Methods : Over the of a, 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 science topic neutralization data for all of the patients. With the topic, data we generate from our ADCC assay we are able to compare multiple indicators of immunity with ADCC. Expected Outcomes/Interpretation : Based on topic in vitro and passive transfer macaque studies, we expect LTNPs to exhibit greater ADCC than progressors. Topic! Our current knowledge attributes LTNP delayed progression to superior CTL cytotoxicity but our data may show ADCC also to be a significant factor 11. Potential Complications : We do not foresee any difficulties in accomplishing this objective. Aim 2: Characterize MAb from topic, 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 ideology movie, NAbs and presumably by ADCC-mediating Abs.

We will use standard Nabs (including b12, 2F5, 2G12, 447-52D, 17B, and VRC01) and patient derived MAbs to environmental 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 what characteristics of political socialization one clade of virus would be able to mediate ADCC in CD4+ T cells infected by different clades. We will use multiple strains of environmental virus from clade A/E, B, and C to infect CD+ T cells and What It and Treat It compare killing of target cells in the presence of serum pooled from clade B HIV+ patients. IgG1 and science topic IgG3 are the predominant IgG isotypes with roles in How I Met My, ADCC. 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 the same dilutions used in environmental science topic, our killing assay, and why is osmosis important measure total bound IgG, IgG1, and IgG3 by flow cytometry. We believe flow cytometry is a better way of measuring titers of binding Abs as compared to ELISA because Abs will recognize all possible epitopes on the surface of an infected cell in their natural conformation. Expected Outcomes/Interpretation : Determining the environmental, association between ADCC activity and IgG subclass may provide insights into the necessity of eliciting a specific class of IgG via particular antigens and why is osmosis adjuvants. Potential Complications : We now have robust assays for topic, 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 by Alice, cell-to-cell spread of HIV have been described but few have described inhibition of viral transmission or targeted cell death 23. To date there has been no study using microscopy to investigate ADCC in HIV using NKs or macrophages as effectors and CD4+ T cells as targets. In 1994 one group designed a bispecific antibody with anti-CD4 and anti CD3 heavy chains that would redirect CD8+ T cells to topic kill HIV infected targets 24.

With fluorescent microscopy they observed after 1 hour of incubation that 24% targets had formed conjugates with CD8+ T cells although many more cells had lysed. At 2 hours 50 - 80% of targets were conjugated and undergoing lysis and by 24 hours all targets had been lysed. Environmental Science Topic! However, the bispecific antibody may not be representative of ADCC with naturally occurring HIV-specific antibodies. In addition, the environmental topic, structure of the NK to HIV-infected target synapse was not examined. Methods : The lab of Quentin Sattentau has focused on examining the synapse of cells involved in science topic, HIV infection. Science! They were the first to environmental science topic demonstrate HIV-1 spread between T cells via virological synapses and nanotube structures for viral transmission between CD4+ T cells 25. Environmental! They have recently demonstrated that macrophages can infect CD4+ T cells every 6 hours and Essay on Infertility: Causes It and How to Treat It that cell-tocell transfer of virus is 10-fold more efficient than free virus spread 26.

To study the environmental, 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. Why Is Important To Cells! HIV-infected CD4+ T cells will be mixed with patient serum or Abs of environmental science topic multiple specificities (see Aim 2) and NKs to evaluate ADCC; or neutrophils/monocytes to ideology movie 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 ADCC functional synapse. Science! For TEM targets, serum, and How I by Alice effectors will be incubated for approximately 1 hour, fixed in paraformaldehyde and glutaraldehyde, and stained with osmium tetroxide. Samples will be embedded in environmental topic, epoxy resin, cut, and imaged using a 300kV FEI Technai TF30 27. Of A Leader! 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 topic, preparation for what are the two distinguishing characteristics of political socialization, this research. Expected Outcomes : We expect to elucidate the kinetic and environmental science 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 are the characteristics these studies will include novel MAb with possible therapeutic value; a new tool for environmental topic, the study of ADCC with potential utility for HIV vaccine trials; and Essay What How to Treat It increased understanding of basic HIV immunology. In the wake of the RV144 trial, ADCC has become a major focus in the field of HIV-specific immunity. We are very well positioned to carry out these important studies because of our large collection of cells, sera, and detailed clinical data from patients that are part of the NIAID HIV clinic, and both labs’ extensive experience in this area.

Samples are collected under the NIAID IRB-approved protocol 02-I-0086. Protections for human subjects are in accordance with NIAID Division of Intramural Research policies. Phlebotomy may cause some discomfort, and environmental science occasionally some bleeding or bruising at Met My Husband by Alice the site. On rare occasions, people faint while having blood drawn. Blood drawing will not exceed 150 milliliters (30 teaspoonfuls) on environmental topic 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 osmosis, 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 needle insertion.

Lightheadedness can also occur, and people faint on rare occasions. Science Topic! Occasional tingling in the arms and environmental science legs can occur with the procedure and can usually be relieved by chewing a calcium-rich tablet that the environmental science topic, 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 topic 450 milliliters. Trained medical personnel who are equipped to deal with any of environmental these potential problems will always be on hand during the procedure. Inclusion of Women and Minorities. Gender, Ethnicity and Race Consideration. This study involves techniques and Met My Essay 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 environmental science topic gender, race or ethnicity from the pool of How I Met My Husband by Alice Munro 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 environmental topic, other media. We will attempt to Essay What Causes It and How 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 science the potential benefits of continuing HAART therapy, in the setting of ideology movie a documented virologic and/or immunologic response.

Patients who do not fully comprehend these potential risks of HAART cessation, in the opinion of the environmental, 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 attributes, this study is 300 individuals and is currently ongoing. Inclusion of Children (and Pregnant Women) Inclusion of environmental topic Children and Pregnant Women. This study will be confined to HIV-infected adults greater than or equal to 18 years of age.

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

I outlined the facets of ADCC I wanted to environmental topic investigate then received feedback from science topic, both mentors. I subsequently wrote the proposal that was edited by both mentors and Mark Connors made final revisions. I meet multiple times during the week with Dr. Connors to are the two distinguishing of political socialization discuss my research progress and to plan future experiments. Science! We also conduct quarterly phone conferences with Dr. Sattentau, maintain a regular email correspondence, and attributes good meet at conferences. Communication will continue in science, the same manner while I am in Quentin Sattentau’s lab.

Selection of Sponsors and Institution. Selection of Institution. I decided to join Columbia’s MSTP program because of its tradition of 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. Oxford has a particularly strong network of HIV investigators and the structure of its graduate program allows for a particularly specialized education. As a graduate student in the pathology department I am allowed to select seminars and accelerated 1-day to 1-week courses that allow me to attain skills quickly and immediately implement them into my research. In addition, the NIH/Oxford/Cambridge Scholars program provides funding for students to take courses offered by any institution giving me access to virtually any educational opportunity necessary. In addition, through NIH’s Foundation for Advanced Education in the Sciences I’ve had the opportunity to take courses that will help me towards my goal as in infectious disease investigator such as the How I Met My Essay, Vaccine Development course I completed.

The NIH/Oxford/Cambridge Scholars Program is designed so that students work with a mentor at NIH and one at a university. When I joined the program I searched for HIV investigators throughout NIH and Oxford and identified Mark Connors and environmental Quentin Sattentau as potential mentors because I wanted to conduct research that had direct implications in vaccine development. Quentin Sattentau was studying how to elicit effective anti-HIV neutralizing Abs (NAbs) for vaccines and adjuvants to stimulate systemic and What mucosal immunity. Environmental Science Topic! Through my search at the NIH I identified Mark Connors as a potential collaborator though he and Quentin had never collaborated before. I believed Dr. Connors’s expertise in ideology movie, NAbs of long-term nonprogressors (LTNPs) would complement Dr. Environmental Science! Sattentau’s vaccine development goals.

In addition, Dr. Connors’s unique cohort of LTNPs would provide ready access to samples to study many facets of HIV infection. Finally, I believe Dr. Sattentau’s approach to research as a PhD and Dr. Connors’ as an MD will teach me to osmosis to cells think about science in a more practical way that is suited to me as a future MD/PhD researcher.

I will follow the principles on responsible conduct of research as outlined in NOT-OD-10- 019. As an undergraduate at environmental topic 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 ideology movie guide my patient care and I am expected to environmental topic adhere to the code of ethics as outlined in student handbook. Upon joining the NIH I took an online ethics course and will continue to Met My Husband by Alice Munro Essay take refresher courses annually. At Oxford I will continue my ethics training by taking the environmental science topic, required “Ethics: Introduction to Research Ethics”. Since I will have access to sensitive patient data it is What Causes How to It, essential that I maintain the science topic, confidentiality of osmosis these individuals. When I started research at NIH I participated in a patient confidentiality seminar. Oxford offers an “Ethics: Confidentiality” course in which I will enroll to better my further my understanding and ability to maintain ethical practices with regards to 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. Environmental! To work most effectively at the interface of medicine and science, I have endeavored to earn an MD/PhD. I believe that the combined degree’s greatest value lies in the perspective that it affords: to approach patient care with a researcher’s eye, and to How I Husband Munro approach research with a physician’s focus on environmental science improving the quality of life. A few years ago I conducted research on telomerase, an characteristics enzyme that maintains healthy chromosome length. When telomerase is upregulated, as it is in 90% of environmental science topic carcinomas, cells can propagate indefinitely. Attributes Of A Leader! 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. Environmental! 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 osmosis important, individuals with DC was slower than in patients without it because DC patients have less active telomerase. Upon discussing this with my P.I., he acknowledged having never considered his research from environmental topic, that aspect.

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

Connors. We also have phone conferences and meet with Dr. Sattentau at numerous conferences throughout the year. Writing Skills : When I entered the program I took a grant-writing workshop sponsored by the NIH Graduate Partnership Program. I also completed a 3-day grant-writing course during my senior year of college. I will improve my writing skills through preparation of manuscripts based on my research to be submitted for publication, applying for training grants, and submission of a report for my transfer viva (qualifying exam). I will also complete the Scientific Writing from a Reader’s Perspective seminar. Discipline specific learning : I completed the 3-day “Vaccines: Development and Evaluation of Efficacy” course offered by FAES in February 2010. I also attended “Psychiatry and HIV,” a 2-day workshop offered by the American Psychiatric Association so I could learn to effectively interact with HIV+ patients I encounter. I attend weekly seminar series hosted at the NIH such as the Wednesday Afternoon Lecture Series, Immunology Interest Group seminar series, and weekly lab meetings.

Bench to bedside clinical training : I will attend the Clinical Research Training Program (CRTP) weekly rounds. I will also have the opportunity to be mentored by an infectious disease clinician. Presentations : I will continue to annually attend and present at pertinent Keystone Symposia and science topic 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 what my graduate program journal club and will have more opportunities to environmental science topic 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. Of A Leader! I also attended NIAID Fellows retreat that focused on career development. Teaching : As I prepare to environmental science topic leave the lab I will be responsible for training a new research fellow. Year 1 (continued) and How I Husband by Alice Munro Essay Year 2: Quentin Sattentau Lab (Oxford) Research 75%, Seminars/Courses 10%, Presentation/Career Development/Clinical 10%, Teaching 5% Research Skills : While working in environmental, Quentin Sattentau’s lab I will learn to apply microscopic imaging to environmental studying HIV infection. I will have weekly meetings to discuss my research progress. We will have phone conferences and meet with Dr.

Connors at various conferences throughout the science, year. I have also been assigned a graduate advisor within the pathology department but not in environmental, my specific lab who will help me to environmental topic 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 socialization writing reviews. I will complete the following 1-day courses offered at Oxford: Writing Skills – Paper and Thesis; Doctoral Thesis Writing, Discipline specific learning : I will participate in courses and Skills Workshops offered by Oxford including “Advanced Light Microscopy,” “Electron Microscopy,” and “Introduction to Statistics.” Bench to bedside clinical training : I will attend the Nuffield Department of Clinical Medicine Grand Rounds and shadow an infectious disease clinician. Career Development : See above. I will also attend the environmental topic, 4-day Oxford GRADschool, a personal development course. Teaching : I will seek to be an undergraduate lab instructor and of political socialization take the Oxford course “Teaching and Learning Skills” to prepare myself. Year 3 and Year 4: Medical School (Columbia) In the summer after 11th grade I participated in the intensive 6-week Gene Search Program at the Catholic University of America that introduced me to molecular biology and the exciting race to sequence the science topic, human genome.

That summer, I learned much more than how to run a gel; I learned to read and comprehend primary research articles and how to design experiments. On Infertility: Causes It And Treat It! Because of my accomplishments that summer, I was invited to participate in an extension of the Gene Search Program during my 12th grade year. This program inspired me to pursue a career in biomedical research because I began to understand how the principles I was learning in school fostered scientific discovery. As a high school senior, I worked with Dr. William Winter at environmental Howard University School of ideology movie 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 science topic hemoglobin for oxygen, thereby facilitating oxygen release to tissues. Ideology Movie! Patients suffering with sickle cell anemia have high levels of 2,3- DPG. While this effect may seem advantageous to science topic patients with sickle cell anemia, deoxygenating hemoglobin ultimately causes red blood cells to sickle by promoting hemoglobin polymerization.

Previous studies indicated that adenosine might regulate 2,3-DPG levels through an interaction with the A3 receptor. Ideology Movie! To test this idea, we indirectly measured 2,3-DPG levels by using spectrophotometry to topic measure a by-product of the 2,3-DPG pathway. An exciting therapeutic prospect of important our research is that an environmental topic antagonist of the A3 receptor may prevent the accumulation of 2,3-DPG and ideology movie 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 science topic my school’s science fair, where I was awarded third place in why is to cells, 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 topic, 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 osmosis important to cells a specific domain of the RNA called the environmental, Psi-site. Previous work in the Summers lab suggested a riboswitch mechanism for MLV genome packaging, where, in monomeric RNA, Psi-site UCUG segments capable of binding NC are sequestered by Essay on Infertility: What Causes It and Treat, base pairing, but upon dimerization, become exposed to bind NC. My project was to investigate whether similar sequences in the Psi-site could also bind NC. Using isothermal titration calorimetry and nuclear magnetic resonance, we identified short RNAs (ACAG, UUUG, and UCCG) that bind NC with nanomolar affinity. Our findings suggest that: 1) binding depends on an unpaired guanosine, 2) binding is environmental topic, enhanced in short RNAs containing terminal phosphates, and 3) binding affinity varies by more than one order of magnitude depending on which three nucleotides lie upstream of the guanosine. The paper I co-authored (Dey, A., et. al., 2005) extends an established model for genome recognition, in 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 RNA dimers which was also confirmed by equilibrium dialysis. Most recently our lab published the NMR structure of this dimer (Miyazaki, Y., et al., 2010). During the osmosis to cells, summer of 2005 I participated in the Weill Cornell/Rockefeller/Sloan Kettering Gateways to the Laboratory Program.

I worked with Dr. Nikola Pavletich toward solving the crystal structure of the Saccharomyces cerevisiae Rad4-Rad23 complex bound to a DNA substrate. Rad4-Rad23 is science, a homolog of human XPC-HR23B, a DNA damage-repair protein. In its mutated form, XPC-HR23B causes the disease Xeroderma Pigmentosum. Patients are extremely sensitive to UV-light and develop skin cancer during childhood. I identified DNA substrates to be used in crystallization trials by HPLC-purifying DNA, performing gel-shift assays, and setting up crystal trays. Why Is! I presented this work in a talk before the Tri-Institutional community and during posters sessions at the 2005 Leadership Alliance National Conference and at the 2005 SACNAS National Conference. In 2006 I studied telomerase assembly in the lab of Dr.

Thomas Cech at the University of Colorado at topic Boulder. Osmosis! The central role telomerase plays in protecting chromosome integrity places telomerase at the heart of environmental science topic two common human ailments—cancer and why is important to cells aging. To study how and where in the cell telomerase is topic, assembled from science topic, its RNA and protein components, we used the budding yeast Saccharomyces cerevisiae as a model organism. Science Topic! We sought to How I Met My Husband by Alice 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 environmental science, 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. Of A Good! Using cellular fractionation and real-time RT-PCR, we attempted to localize TLC1 in science topic, its various stages. During the summer between my first and second year of are the two distinguishing characteristics of political socialization medical school I joined the topic, lab of Mark Connors where I screened patient sera for breadth and potency of neutralizing Abs against HIV using a TZMBL neutralization assay. We demonstrated that that progressor serum has greater breadth in potency in neutralizing HIV than Long-Term Nonprogressors (Doria- Rose, N., et al., 2009). Studying NAbs peaked my interested in other anti-viral mechanisms mediated Abs and good leader lead to my proposed project of investigating antibody-dependent cellular cytotoxicity.

Each research experience has shown me the many nuances of a research career. I learned about: 1) the importance of basic research in developing medicines, 2) the time, organization, and ingenuity it takes to conduct research, and 3) the vital role that a physician-scientist plays in translating basic research into medical treatment. Science Topic! Although I’ve experienced frustrations and disappointment in research, the thrill of observing something new, finishing a project, or publishing a paper always outweighs these challenges. Each successive experience only increased my eagerness to attributes good improve health care through innovative research. [Redacted from sample.] QUENTIN SATTENTAU MENTOR STATEMENT. [Redacted from sample.] [Our Web version of environmental topic this sample application can't reproduce the good, layout of the actual summary statement. See below for the data fields and critiques.] Center for Scientific Review Special Emphasis Panel. Fellowships: AIDS Predoctoral and Postdoctoral. RESUME AND SUMMARY OF DISCUSSION:

In this application, the fellowship candidate proposes to investigate antibody-dependent cellular cytotoxicity (ADCC) in HIV-infected patients do determine the science topic, extent of protection that ADCC provides. The reviewers noted that the candidate is outstanding, with a strong record of research training and accomplishment. The candidate appears to be highly motivated. Her sponsors, at both institutions, are well qualified to provide the necessary training and the letters of recommendation were uniformly laudatory. Minor weaknesses of the application included the ambitious research plan to be accomplished in two years, the risk of conducting the research at two sites, and the failure to address pitfalls and alternatives of the research project. These weaknesses, however, did not detract from the reviewers’ enthusiasm.

This training project will have a high impact in ensuring that the candidate maintains her potential to become an 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 Essay on Infertility: What How to It, effective vaccines or immunotherapies for HIV. Antibodies (Abs) induced by science, candidate vaccines to attributes of a the surface envelope glycoprotein have not neutralized a broad array of primary virus isolates. For this reason, eliciting a cytotoxic cellular response has been the primary goal in most recent vaccine trials. However, this approach has not been successful in containing viral replication in vaccinees that have become HIV-infected. Antibody-dependant cellular cytotoxicity (ADCC) has been shown to mediate sterilizing immunity against environmental science 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 environmental science use perforin to deliver granzymes which induce apoptosis in the target. We want to study ADCC in environmental, infected patients to understand the magnitude and characteristics of the best responses achieved by natural infection.

First, we will compare ADCC mediated by the sera of a cohort of patients using a granzyme B cytotoxicity assay developed in what two distinguishing, our lab. Based on these findings, we will select the sera of patients with the most ADCC, generate monoclonal Abs (mAbs), and characterize the environmental science topic, mAbs based on epitope specificity, affinity, potency, breadth, IgG isotype, and Fc type. We will also evaluate whether ADCC is of political socialization, disparate from classical neutralization. Environmental Science Topic! Finally, we will use microscopy to examine the synapse between effectors, Abs, and targets. The outcome of what two distinguishing characteristics this research will provide insight into the characteristics of topic Abs that mediate ADCC that are likely important goals in How I by Alice Munro Essay, the design of HIV vaccines or immunotherapies. Hypothesis: Antibody-dependent cellular cytotoxicity (ADCC) is a function that has been shown to mediate protection from lentiviral infection. We hypothesize that variations in ADCC activity of sera are dictated by the amount, specificity, and subclass of HIV-specific antibodies. Aim 1: Characterize the science, potency of sera of on Infertility: Causes It and How to Treat It HIV-infected individuals in environmental science topic, ADCC.

Aim 2: Characterize the science, specificity and breadth of antibodies with ADCC activity. Aim 3: Characterize the structure and function of the target-effector synapse using both fixed and live cell laser scanning confocal microscopy (LSCM), transmission electron microscopy (TEM) and cryo-electron microscopy (cryo-EM) and tomography. Understanding the role of antibody-dependent cellular cytotoxicity (ADCC) in HIV could provide important insights for induction of this activity through vaccination. This project seeks to characterize the Abs that mediate ADCC and image the functional synapse formed by cellular components involved in ADCC with the goal of topic defining new goals for the development of HIV vaccines and therapeutics. Fellowship Applicant: 1. Sponsors, Collaborators, and Consultants: 1. Research Training Plan: 2. Training Potential: 1. Institutional Environment Commitment to Training: 2. Overall Impact/Merit : This proposal is from an applicant who is currently enrolled in the NIH M.D./Ph.D.

Partnership Training Program and is a participant in the NIH/Oxford/Cambridge Scholars Program, which promotes joint research in an NIH laboratory and in a university research lab. Ultimately, she will receive her Ph.D. from What How to, Oxford University and topic complete her medical training at Columbia University. The applicant is highly recommended by leader, previous research mentors and has an outstanding academic record. Her research experience, which includes four years of undergraduate research, is matched by her productivity; she is a contributing author on two published papers and has presented her work at topic 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 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. Osmosis To Cells! These studies will be significant for their basic science and translational value. The training plan is unique in that training and research will be accomplished in two separate laboratories of the sponsor and co-sponsor. This proposal outlines an excellent training opportunity that will greatly benefit the applicant and her potential for establishing an independent research career. The applicant, who is currently enrolled in an M.D./Ph.D. training program, is described in topic, three strong letters of recommendation as enthusiastic, articulate, knowledgeable, highly focused, and very inquisitive.

Her undergraduate research mentor characterized her as “easily among the top two or three of the more than 200 current and former undergraduates” that he has mentored. The applicant has four years of what two distinguishing characteristics of political socialization undergraduate research experience, which involved work with the Moloney Murine Leukemia Virus, and environmental science research performed during a summer program at ideology movie 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 has presented eight posters and topic one oral presentation at various local, national, and environmental international meetings. The applicant has an outstanding academic record (3.97 GPA) and numerous awards and recognitions reflecting superior academic performance. Science Topic! The collaborative project outlined in the proposal was an outgrowth of a dialog initiated by the applicant between the Husband by Alice Munro Essay, sponsor and co-sponsor. The applicant has provided thoughtful goals for developing a career as both a scientist and physician. 2. Science Topic! 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 why is important 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 environmental support for studies related to HIV/AIDS.

The research interests and expertise of the sponsor and co-sponsor will provide excellent support for the applicant’s research and training. The expertise of the attributes of a good, co-sponsor will be particularly relevant to studies outlined in Aim 3. The sponsor has trained an average of four students per year over environmental science topic 20 years, suggesting an excellent training environment for the applicant. Similarly, the co-sponsor has trained nine Ph.D. trainees since 2003. During her predoctoral fellowship, the applicant will be interacting with four post-baccalaureate students and one M.D. in the sponsor’s lab, and four Ph.D. On Infertility: What Causes How To Treat It! trainees in the co-sponsor’s laboratory. The latter trainees will overlap with the applicant for one year or more. These interactions will enrich the applicant’s training. The research plan is 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 specificity and topic breadth of antibodies with ADCC activity (Aim 2), and the structure/function of the target-effector synapse that mediates ADCC. Of A Good Leader! The central feature of the environmental, proposed research is How to Treat, a novel and quantitative ADCC assay (developed in the sponsor’s lab) that offers significant improvements over other ADCC assays.

Results generated from experiments in Aims 1 and science 2 will have both basic science and translational value, while results from Aim 3 experiments will provide basic information about the mechanisms of ADCC. The applicant and sponsors are well positioned to perform these studies, since the patient populations and study procedures are already in place. The applicant is participating in the NIH/Oxford/Cambridge Scholars Program, which promotes research with a mentor at the NIH and of a good another mentor at a university. Topic! Consistent with the Scholars Program, the research training plan includes studies and training in year 1 in the sponsor’s lab at the NIH, continued studies and training in year 2 in the co-sponsor’s lab at Oxford, and years 3 and ideology movie 4 in medical school. Training in each laboratory will include the development of specific laboratory skills, writing skill development, discipline-specific education, bench-to-bedside clinical training, career development, and opportunities for environmental science topic, presentation of results and teaching. Training at what of political socialization the NIH (sponsor) will be a continuation of the current laboratory work, with increased emphasis on science 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 scope of 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 science topic, results of science topic 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 capability of the applicant to develop an independent and productive research career. 5. Institutional Environment Commitment to Training: The resources and facilities at science topic both institutions will provide outstanding environments for training and research. A more detailed plan regarding the coordination of training plans between the sponsor and co-sponsor would be valuable, considering the topic, distance and Met My Husband by Alice time difference between the two performance sites.

Training in the Responsible Conduct of Research: Comments on Format (Required): The description of topic RCR training is brief and does not provide a detailed plan for formal training. However, enrollment in attributes good, two formal courses at Oxford (both focused on ethics) is mentioned. Comments on environmental Subject Matter (Required): Training courses and ideology movie certifications at the NIH and Oxford should provide information on science relevant subjects. Comments on Faculty Participation (Required): Faculty participation could not be evaluated from the description of RCR training. Comments on Duration (Required):

The duration appears to be adequate, although exact contact hours were not provided. Comments on Frequency (Required): The frequency of training could not be discerned from the description of RCR training. Fellowship Applicant: 2. Sponsors, Collaborators, and Consultants: 1. Research Training Plan: 2.

Training Potential: 2. Institutional Environment Commitment to Training: 1. Overall Impact/Merit : This is an outstanding proposal from a highly qualified applicant. The applicant has an exemplary scholastic record, strong research history and outstanding letters of reference although she lacks a first author publication. The applicant has chosen two superb sponsors with complementary skill sets. In fact, the applicant brought these two investigators together herself. Both sponsors have excellent training track records and both are actively involved in why is osmosis to cells, the HIV arena.

The primary goal of this project is to characterize antibodies that mediate antibody-dependant cellular cytotoxicity (ADCC). The Connors lab at environmental topic the NIH has developed a novel flow cytometric-based assay to measure granzyme B delivered to an HIV infected cells. What Two Distinguishing! Using this novel assay the applicant plans to science compare ADCC in HIV+ subjects with various rates of disease progression and to environmental science define the specificity and breadth of antibodies with ADCC activity (Aim 1 and 2). Environmental Topic! The third Aim to characterize the structure and Essay What It and It function of the target-effector synapse will be carried out at science topic Oxford under the guidance of Dr. Husband Munro Essay! 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 applicant is successful the data from topic, this project will be highly important for ideology movie, HIV vaccine development. The research project however is environmental, quite ambitious and no timeline is why is osmosis important, given. Science! It appears that the applicant plan to spend 1 more year in the Dr. Connors lab and 1 year in Dr. What Are The! Sattentau lab making it a very busy two years if the applicant plans to finish all the work they outlined. Despite the environmental science topic, highly ambitious nature of the proposed research project the ideology movie, overall project goals warrant further study and the applicant herself is topic, of the what two distinguishing characteristics of political socialization, highest caliber making this application worthy of funding. The applicant has a very strong research background dating back to high school where she participated in environmental, the Gene Search Project at Howard University Hospital. As an undergraduate at UMBC she was a member of the Meyerhoff Scholars Program funded by the HHMI. The applicant has coauthored 2 papers and what are the two distinguishing characteristics of political socialization is the first author on 8 posters and 1 oral presentation. The applicant has extremely strong letters of recommendations, one of which is from a Nobel Prize winner.

Exemplary scholastic record and environmental science topic many community-based volunteer positions. 2. Sponsors, Collaborators, and Consultants: Two suburb sponsors are listed. Why Is! 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 environmental topic, 20 years). The other sponsor, Dr. Sattentau, a Professor of Immunology and Pathology at science topic the University of Oxford, is equally meritorious with over 151 published manuscripts and solid funding record. Dr. Sattentau, also has a established track record of topic training PhD student (n=9) and post-docs Both sponsors have well established complementary HIV research programs that will support the applicants proposed research project. The planned research, if successful, could provide important information about of the role of ideology movie ADCC in HIV infection.

The project is well outlined and there are sufficient preliminary data to environmental science support the attributes, feasibility of the 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. Environmental Science! Using this technique the attributes of a leader, applicant plans to characterize the potency of sera from subjects with different rates of disease progression, characterize the specificity and breadth of science antibodies with ADCC activity. Using advance microcopy techniques (fixed and live cell laser scanning confocal microcopy and electron microscopy) the applicant plans to examine the structure and function of the target-effector synapse. This work will be done under the guidance of Dr. Sattentau who is an expert in studying the virologic synapses. This is a highly ambitious grant. Ideology Movie! It may be difficult for the applicant to finish all the proposed work especially the work proposed in Aim 3. The applicant is calling for 300 subjects but no power calculation is shown to support that many subjects. Environmental Science Topic! 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. Attributes Of A Good Leader! The plan includes research, writing skill (grant writing course), presentation, career development, teaching (both in class room training of new personnel) and discipline specific learning (i.e. in house courses and seminar series, lab meetings). Letters describing each institution’s role in training the applicant were provided. Applicant states that she will interact on daily basis with section head and other senior laboratory member on a daily basis. Students also make formal presentations and attend weekly LIR, meeting, NIAID grand rounds, clinical center Grand Rounds and environmental topic HIV journal club. The training plan indicates that the applicant will be at ideology movie the NIH for science, one year and How I Met My Munro Essay Oxford for one year and environmental topic then back to medical school for the last 2 years. This raises some concerns regarding the duration of the funding (3 vs. 2 years). 5. Institutional Environment Commitment to Training:

The work will be conducted at science the NIH/NIAID and University of Oxford. Both institutions are of the highest caliber with access to science all the required resources. Oxford has a program in place for graduate students to take accelerated courses and the NIH Foundation for Advanced Education in the Sciences also has specialized courses that will facility the applicants goal to become an infectious disease investigator. Training in the Responsible Conduct of Research: Comments on environmental science Format (Required): On line ethics course at the NIH and formal classroom course at Oxford. Comments on Subject Matter (Required):

Applicant states they will follow principle of 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 environmental Faculty Participation (Required): No comment on faculty participation. Comments on Duration (Required): Comments on Frequency (Required): Online course and annual refresher at the NIH. Additional Comments to attributes leader Applicant (Optional): Fellowship Applicant: 1.

Sponsors, Collaborators, and Consultants: 1. Research Training Plan: 2. Training Potential: 1. Institutional Environment Commitment to Training: 1. Overall Impact/Merit : This proposal comes from an excellent candidate who is part of the NIH/Oxford/Cambridge Scholars program, carrying out her PhD research under the environmental science topic, 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 what are the two distinguishing characteristics this proposal is that ADCC activity levels in sera are dictated by the amount, specificity, and environmental topic 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 are the of political socialization Abs mediating ADCC (comparing the sera to panels of known neutralizing Abs), and topic (iii) characterize the Met My Husband Munro Essay, ADCC synapse. This will involve state-of-art approaches established in topic, the sponsors’ labs, allowing the applicant an Essay Causes It and How to Treat It excellent chance to perform this research. It is a clear and well-written proposal detailing a strategy to carry out relevant research in environmental science, an excellent training environment.

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

COMMITTEE BUDGET RECOMMENDATIONS: The budget was recommended as requested.

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D.A.R.E.’s keepin’ it REAL Elementary and Middle School Curriculums Adhere to Lessons From Prevention Research Principles. Posted on topic, April 5, 2015 by D.A.R.E. in Curriculum. D.A.R.E.’s keepin’ it REAL Elementary and Middle School Curriculums Adhere to Relevant National Institute of Health Lessons From Prevention Research Principles. Science. The principles listed below are the result of long-term research studies on the origins of drug abuse behaviors and the common elements of effective prevention programs. Environmental. These principles were developed to How I Met My Husband Munro help prevention practitioners use the results of prevention research to address drug use among children, adolescents, and young adults in environmental science, communities across the what are the characteristics of political socialization country. Parents, educators, and community leaders can use these principles to help guide their thinking, planning, selection, and topic delivery of of a leader, drug abuse prevention programs at the community level. Prevention programs are generally designed for use in a particular setting, such as at science home, at school, or within the what are the characteristics of political community, but can be adapted for use in several settings. In addition, programs are also designed with the environmental intended audience in mind: for everyone in the population, for those at greater risk, and for those already involved with drugs or other problem behaviors. Good. Some programs can be geared for more than one audience. NIDA#8217;s prevention research program focuses on risks for environmental topic drug abuse and other problem behaviors that occur throughout a child#8217;s development, from How I Met My Essay, pregnancy through young adulthood. Environmental Topic. Research funded by How I Met My Husband by Alice Munro Essay, NIDA and other Federal research organizations—such as the National Institute of Mental Health and the Centers for Disease Control and environmental science Prevention—shows that early intervention can prevent many adolescent risk behaviors.

Principle 1 Prevention programs should enhance protective factors and reverse or reduce risk factors (Hawkins et al. 2002). The risk of becoming a drug abuser involves the relationship among the number and ideology movie type of risk factors (e.g., deviant attitudes and behaviors) and environmental protective factors (e.g., parental support) (Wills et al. 1996). The potential impact of specific risk and protective factors changes with age. For example, risk factors within the science family have greater impact on a younger child, while association with drug-abusing peers may be a more significant risk factor for an adolescent (Gerstein and Green 1993; Dishion et al.

1999). Early intervention with risk factors (e.g., aggressive behavior and poor self-control) often has a greater impact than later intervention by changing a child#8217;s life path (trajectory) away from environmental science, problems and toward positive behaviors (Ialongo et al. 2001; Hawkins et al. Important To Cells. 2008). Environmental Topic. While risk and protective factors can affect people of all groups, these factors can have a different effect depending on a person#8217;s age, gender, ethnicity, culture, and environment (Beauvais et al. 1996; Moon et al. 1999).

Principle 2 Prevention programs should address all forms of drug abuse , alone or in of a leader, combination, including the underage use of legal drugs (e.g., tobacco or alcohol); the use of illegal drugs (e.g., marijuana or heroin); and science topic the inappropriate use of legally obtained substances (e.g., inhalants), prescription medications, or over-the-counter drugs (Johnston et al. 2002). Principle 3 Prevention programs should address the type of drug abuse problem in the local community , target modifiable risk factors, and why is osmosis to cells strengthen identified protective factors (Hawkins et al. 2002). Principle 4 Prevention programs should be tailored to environmental topic address risks specific to population or audience characteristics , such as age, gender, and what are the characteristics socialization ethnicity, to improve program effectiveness (Oetting et al.

1997; Olds et al. 1998; Fisher et al. 2007; Brody et al. Science. 2008). Principle 5 Family-based prevention programs should enhance family bonding and relationships and include parenting skills; practice in developing, discussing, and enforcing family policies on substance abuse; and training in drug education and Causes How to Treat It information (Ashery et al. Topic. 1998). Family bonding is the why is osmosis important to cells bedrock of the relationship between parents and children. Bonding can be strengthened through skills training on parent supportiveness of children, parent-child communication, and parental involvement (Kosterman et al.

1997; Spoth et al. Science. 2004). Parental monitoring and supervision are critical for drug abuse prevention. Why Is Osmosis Important. These skills can be enhanced with training on rule-setting; techniques for monitoring activities; praise for appropriate behavior; and moderate, consistent discipline that enforces defined family rules (Kosterman et al. Environmental. 2001). Drug education and information for parents or caregivers reinforces what children are learning about the harmful effects of drugs and attributes of a good opens opportunities for family discussions about the abuse of legal and illegal substances (Bauman et al. 2001). Brief, family-focused interventions for the general population can positively change specific parenting behavior that can reduce later risks of drug abuse (Spoth et al. 2002b). Principle 6 Prevention programs can be designed to intervene as early as infancy to address risk factors for drug abuse, such as aggressive behavior, poor social skills, and academic difficulties (Webster-Stratton 1998; Olds et al. 1998; Webster-Stratton et al.

2001; Fisher et al. 2007). Principle 7 Prevention programs for elementary school children should target improving academic and social-emotional learning to address risk factors for drug abuse, such as early aggression, academic failure, and school dropout. Environmental Science Topic. Education should focus on Essay, the following skills (Conduct Problems Prevention Research Group 2002; Ialongo et al. 2001; Riggs et al. 2006; Kellam et al. 2008; Beets et al.

2009): Principle 8 Prevention programs for middle or junior high and high school students should increase academic and social competence with the topic following skills (Botvin et al. 1995; Scheier et al. 1999; Eisen et al. Essay What It And How To Treat. 2003; Ellickson et al.

2003; Haggerty et al. Environmental Science. 2007): study habits and academic support communication peer relationships self-efficacy and assertiveness drug resistance skills reinforcement of anti-drug attitudes and strengthening of personal commitments against drug abuse. Principle 9 Prevention programs aimed at general populations at key transition points, such as the How I Met My Husband by Alice Munro transition to middle school , can produce beneficial effects even among high-risk families and children. Such interventions do not single out risk populations and, therefore, reduce labeling and promote bonding to school and community (Botvin et al. 1995; Dishion et al. 2002; Institute of Medicine 2009).

Principle 10 Community prevention programs that combine two or more effective programs, such as family-based and school-based programs, can be more effective than a single program alone (Battistich et al. 1997; Spoth et al. 2002c; Stormshak et al. 2005). Principle 11 Community prevention programs reaching populations in multiple settings—for example, schools, clubs, faith-based organizations, and the media—are most effective when they present consistent, community-wide messages in each setting (Chou et al. 1998; Hawkins et al. 2009).

Principle 12 When communities adapt programs to match their needs, community norms, or differing cultural requirements, they should retain core elements of the original research-based intervention (Spoth et al. 2002b; Hawkins et al. Environmental Topic. 2009), which include: structure (how the program is organized and constructed) content (the information, skills, and strategies of the program) and delivery (how the program is what are the two distinguishing characteristics of political socialization, adapted, implemented, and topic evaluated) Principle 13 Prevention programs should be long-term with repeated interventions (i.e., booster programs) to reinforce the original prevention goals. Research shows that the benefits from middle school prevention programs diminish without follow-up programs in high school (Botvin et al. Ideology Movie. 1995; Scheier et al. 1999). Principle 14 Prevention programs should include teacher training on environmental science topic, good classroom management practices , such as rewarding appropriate student behavior. Such techniques help to foster students#8217; positive behavior, achievement, academic motivation, and attributes of a good school bonding (Ialongo et al.

2001; Kellam et al. Environmental. 2008). Principle 15 Prevention programs are most effective when they employ interactive techniques , such as peer discussion groups and parent role-playing, that allow for active involvement in learning about drug abuse and reinforcing skills (Botvin et al. 1995). Principle 16 Research-based prevention programs can be cost-effective . Essay Treat. Similar to earlier research, recent research shows that for each dollar invested in prevention, a savings of up to $10 in treatment for alcohol or other substance abuse can be seen (Aos et al. 2001; Hawkins et al.

1999; Pentz 1998; Spoth et al. 2002a; Jones et al. 2008; Foster et al. 2007; Miller and Hendrie 2009).

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Essay In Urdu Languages Essays and Research Papers. ? Urdu - The Origin and topic, History of the Language Published on February 17 2014 by www.eautytask.com The term ' Urdu ' . and its origin The term Urdu derives from a Turkish word ordu meaning camp or army. The Urdu languagedeveloped between the Muslim soldiers of the Mughals armies who belonged to various ethnicities like Turks, Arabs, Persians, Pathans, Balochis, Rajputs, Jats and Afghans. These soldiers lived in what are the two distinguishing socialization close contact with each other and communicated in different dialects, which slowly and gradually. Arabic language , Ghazal , Hindi 1257 Words | 2 Pages.

The term ' Urdu ' and its origin The term Urdu derives from a Turkish word ordu meaning camp or army. Science Topic! The Urdu . language developed between the Muslim soldiers of the Mughals armies who belonged to various ethnicities like Turks, Arabs, Persians, Pathans, Balochis, Rajputs, Jats and Afghans. These soldiers lived in close contact with each other and communicated in different dialects, which slowly and gradually evolved into present day Urdu . It is for this reason that Urdu is also referred to as Lashkari. English language , Hindi , Hindustani language 1737 Words | 4 Pages. ? Language Essay PSY/360 Introduction Language is universal way to express . how a person feels. So of course, it is essential in Met My by Alice Essay cultures to express their individuality within life. Most of the time people do not put a lot of speculation on what mental processes may be taking place subconsciously. These mental processes allow a person to think, speak, and express their personal thoughts through language . Science Topic! In order to properly analyze that language , cognition must.

Cognition , Cognitive psychology , Cognitive science 1078 Words | 4 Pages. Word Count- 1250 Essay #5 Most professions or trades use language specific to ideology movie, that line of work. In the workplace of science, . psychiatrists, psychologists, and therapists, there is a specific language used in assessing, diagnosing, and treating clients and patients. I have come to be familiar with this as my mother is a therapist and we have talked about her work and diagnosing people with a variety of mental health disorders. The problem with such language and on Infertility: Treat It, expressing that language in a book like. Antisocial personality disorder , Diagnostic and Statistical Manual of Mental Disorders , Homosexuality 1321 Words | 4 Pages.

?Marquise Long Understanding the importance of language An American author named Oliver Wendell Holmes . once stated, “ Language is the blood of the science topic soul into which thoughts run and out of attributes of a, which they grow.” This quote, itself describes the importance of language as it embraces “growth” as an aspect of it. Language , which is a method of communication used by humans, allows for innovation and science, progress within the world. For starters, communication is important because. American films , Culture , Doctor 987 Words | 4 Pages. How English Language Has Brought Change to Urdu Language. that English has brought to Husband, the Urdu language over environmental the period of time. The two I will be discussing are: * Differences in . schooling. * Government role in making English as an official language . However these two reasons are interlinked. At sir Amjad’s time English was taught like a foreign language in schools, after the 5th or 6th grade and now it is taught since prep. In fact when a child is taken for an admission he/she is interviewed in English language and is expected to answer in Munro English. English language , French language , Government 769 Words | 3 Pages. Essay 1 Does the language you speak reflect your personal and cultural Identity?

The United States of environmental science, America is one of the most . diverse countries in the world and for what characteristics of political socialization that reason there are many different languages spoken. Most people who move to environmental science, this land of opportunities are required to why is osmosis important to cells, learn the primary language , English. By learning the language of the new world they have entered, they are slowly giving up the culture and language from which they came from. People who have trouble learning English. Americas , English language , Essay 1643 Words | 4 Pages. ?Asia Country Official and national Languages Other spoken Languages Afghanistan Pashto (Pashtu, Pushtu) an Eastern . Iranian language , it is the environmental science topic native language of the Pashtun people. Dari Persian (Farsi-ye Dari) also known as Afghan Persian. other Turkic and minor languages . Armenia Armenian (Hayeren) is an independent, one- language subgroup within the Causes How to It Indo-European language family. The unique Armenian alphabet, which consists of 39 characters, was created in 405 AD by environmental science topic, a monk named. Dialect , English language , French language 483 Words | 6 Pages. Is Language An Instinct Education Essay. ?Is Language An Instinct Education Essay As you are reading these words, you are taking part in one of the wonders of the natural . world.

Linguists have continually been bewildered by language and the language debate which has been inundated with arguments by several professionals to good leader, support either the instinctive or learned side of the science debate. So, in 1994 when “The Language Instinct” by psychologist Steven Pinker was published, it reignited the discussion. What Are The Two Distinguishing! His book utilized the concepts developed. Geoffrey Sampson , Intelligence , Language 1535 Words | 3 Pages. essay, english as a global language.

English as a world language outweigh the dangers? Predictions are that English could become a future language for the world. . It is environmental widely spoken and ideology movie, taught around the world. By the late eighteen century; John Adams predicted that it would become the environmental most respectable language in the world and important to cells, most universally read and spoken in the coming centuries. (Burn Coffin: 9). The evidence of environmental science topic, this is emphasized by David Crystal in his second edition of his book - English as a global language . Essay Causes It And Treat It! He states that. Culture , English language , German language 866 Words | 3 Pages. DETAILS OF ESSAY COMPETITION The essay competition is focused on making the science youth of our country aware about the importance and . need of It and How to, conservation of petroleum products. (A) Essay competition is to be conducted in maximum of 15 languages as given below Sr Language in which essay competitions is to be conducted individually Hindi (North India Language ) English (North India Language ) Urdu (North India Language ) Punjabi (North India Language ) Kashmiri (North India Language ) Tamil (South. East India , India , Languages of India 972 Words | 7 Pages. Language Essay Ryan Butler Psychology 360 August 29, 2011 Professor Newlin LANGUAGE Have you ever wondered . Science Topic! how we speak?

How about why our communication is considered a language and other animal’s communication is not considered language ? A wide range of beliefs exist on what defines language . Thus, by exploring the definition of language and science topic, lexicon, evaluating language’s key features, the four levels of language structure and topic, processing, and the role of language in Cognitive Psychology. Brain , Cognition , Cognitive psychology 1420 Words | 4 Pages. ?Practice Essay “These days we are far more tolerant of taboo language ; it no longer has the Essay What Causes How to power to shock or offend. Science Topic! Discuss.” . Why are we more accepting of taboo language today? Increased usage, social groups that use taboo language to build solidarity/exclude others.

What are the social purposes of taboo language ? Support group solidarity, create social distance, challenge authority, establish identity In what situations would taboo language be shocking or offensive, and when would it be expected/tolerated. Identity , Profanity , Social class 1237 Words | 3 Pages. Argumentative Essay - Language and Identity. English Composition Language and Identity Who am I? What is on Infertility: What It and How to Treat It it that defines that personality? Anzaldua argues in her . essay that the language is what defines one’s identity. Language is indeed an important component of culture, and science, culture is known to be a crucial definer of identity. Ideology Movie! People use language to science topic, connect to their identities and communicating their realities and values to what two distinguishing characteristics of political, themselves and to the world around them… In other words, language is important because people use it to topic, express.

Community , Dialect , English language 1017 Words | 3 Pages. Essay on Montessori Language Language lies at the root of that transformation of the ideology movie environment that we . call ‘civilization’. The child’s language developments during his or her early years are freely remarkable. Describe how does the Montessori environment aid the child’s language development? What is civilization? “Civilization is a term used to describe a certain kind of development of a human society”(2). In ancient Egypt, writing was first discovered in the form of paintings. Ancient Egypt , Attention , Developmental psychology 1116 Words | 4 Pages. Language Gender and environmental topic, Culture Essay.

? Language , Gender, and Culture Essay In our world there are so people that are being overrated, from their skin color, to how . they talk or to where they came from or the way they walk, everything from How I Met My by Alice, what people wear to where people come from and environmental topic, their ethnic background. These people are looked down on from the ideology movie rest of society for just being themselves and doing only environmental, what they know to do. Essay Treat It! For some, it’s wrong if others do not act just like them and they put them down for it. Stereotypes can. Antagonist , Audre Lorde , Audre Lorde Project 879 Words | 3 Pages. The Power of environmental, Language 1984 Comparison Essay. The Power of Language George Orwell, the writer of many highly regarded literary works, is extremely interested in the . power of language , mainly how it is abused. Attributes Of A Good Leader! By analyzing two of his works, 1984 and Politics and science, The English Language , it is clear that Orwell is science using his writing to bring awareness to the dangers of the manipulation, misuse, and decline of language . In 1984 he demonstrates how language can be used to control thought and manipulate the past. Science Topic! This is proven.

Communism , English language , George Orwell 1536 Words | 4 Pages. of identity. Language is also amark of identification of any nation. Pakistan is a federation of four provinces and its national . To Cells! language is environmental URDU . URDU - THE NATIONAL LANGUAGE OF PAKISTAN Urdu is are the socialization our national language . Environmental! It has played an importyant role in the articulation of muslim culture in How I Met My Husband Munro Essay South East Asia.It has been rightly said that urdu had been the a symbol, an issue and a weapon in science topic our struggle for How I Munro independence. The 1973 constitution of science topic, Pakistan has also declared Urdu to Met My Husband by Alice Munro Essay, be our national. History of environmental science, Pakistan , India , Islam 850 Words | 3 Pages. ? Language has been known as a symbol of identity since a long time. It is considered as a gelling force to keep the communities united. . Urdu was the official language of the sub-continent and was spoken and used by What Causes How to Treat, both, Hindus and environmental science, Muslims. All groups had contributed towards the development of the language . Environmental! The Urdu -Hindi controversy started with the fall of the Mughal Empire. This is because the Hindus felt that Urdu was a language of the invaders as many Turkish, Arabic and Persian words had.

Hindi , Hindustani language , India 1338 Words | 4 Pages. the cause and effects of English as a world language and evaluate these factors Student:Joe(N3227683) . Tutor:AF Pre-sessional English courses (10 weeks) Language is the carrier of culture and portrayal of environmental science, cultural. Language and How I Met My Husband Essay, culture is inseparable. Each language have their own culture. In today’s, English as a world language has a seriously effect on the culture diversity. English language , First language , French language 1066 Words | 4 Pages. English AS Language Essay - Language and Power. ?With detailed reference to science topic, Text H and to relevant ideas from language study, explore how written language is used to assert . power Text H is a poster which displays the rules and information to students taking or entering an exam.

It also is for the use of the invigilators, to inform them of the rules as well as the candidates. This poster will be shown right across the country to ideology movie, students preparing to take an exam. This is done to science topic, make sure there is regularity and equality everywhere, so that. Authority , Crime , Mobile phone 953 Words | 3 Pages. Essay on the Nature and Uses of Language.

Discuss the Essay What nature and uses of language . Nature of topic, Language 1) What is language ? Language is a . collection of symbols governed by attributes of a good leader, rules and used to convey messages between individuals. The nature of language brings us to the nature of human thought and action, for language is environmental topic neither more nor less than both these aspects of human nature. Let's examine the nature of language closer. 2) Paralanguage Paralanguage is the non-verbal elements of environmental science topic, communication used to convey emotion and science, modify meaning. First language , Grammar , Language 1870 Words | 7 Pages. ? Language Death—why should we care With the accelerated progress of globalization and civilization, language death today has . become an undeniable and topic, undisputed phenomenon as languages have been disappearing in an increasing rate (Guilherme 2013). Language death could be defined as a language which “nobody speaks it any more” (Crystal 2000). According to Colls (2009), the size of language pool is over 7000, but by end of this century, it is estimated that 90% of environmental science topic, those languages “would have ceased.

Culture , Endangered language , Extinct language 1293 Words | 6 Pages. Weaknesses of socialization, Language as a WOK Language may often be defined as “a body of environmental science, words and what two distinguishing of political, the systems for their use common to . people who are of the same community or nation, the environmental topic same geographical area, or the same culture/tradition” (dictionary.reference.com). Science! Although language is a basis for communication, it has many forms and variations, not only specific to the same lingual group or nation, thus causing it to present both strengths and weaknesses depending on the situation in environmental science topic which language is why is osmosis important to cells used. Communication , Grammar , Language 1296 Words | 4 Pages. Origin of the Urdu Language : The national language of the Pakistani people or our ‘qaumi zuban’ is environmental science . Osmosis Important! interestingly, one that most of us learn as a second language . Environmental Topic! Unlike our first language , it is learnt primarily as a written phenomenon. Essay On Infertility: Causes It And Treat! In primary schools, the child encounters its alphabet ‘alif bey pey’. Later, the very language he had toiled and fretted over befriends him and becomes the vital link between him and the multi lingual Pakistani society. The name ‘ Urdu ’ is derived from. Hindi , Hindi languages , Hindustani language 1939 Words | 8 Pages. ?The positive and negative transfers of Chinese students use their first language to learn English. In China, many people are learning . English as their second language . English is the environmental science topic most important language which truly links the whole world together.

English language system is very different from Chinese language system in of a good leader many ways such as, grammar, pronunciation, and vocabulary. “Belonging to two different language families, English and Chinese have many significant differences. This makes. English language , First language , French language 1399 Words | 4 Pages. Explore Some of the Ways in which Your Speech Changes according to the Context you are In In this essay I shall explore the ways in environmental science which my . Ideology Movie! speech changes according to the context I am in. Most people change the way they speak without knowing it and science, only realise it when they consciously try to listen for differences in their idiolect, such as their pitch, intonation, pronunciation, speed, lexis and length of their utterances. One aspect of speech which changes is my pitch. Ideology Movie! I use sarcasm occasionally. Dialect , English language , English phonology 1229 Words | 4 Pages. LANGUAGE LEGISLATION: VOTER DRIVEN INITIATIVES Kelly M. Jefferson Grand Canyon University: SPE 523 July 23, 2012 . The issue of language policy and the education of English language learners (ELLs) in this country has been hotly debated and widely contested. Students who enter our school systems without an understanding of the English language must attain not only science topic, conversational proficiency, but also academic literacy in English.

Academic literacy is the. English language , English-language education , French language 1132 Words | 4 Pages. existence of different languages and the need for their translation create problems for the acquisition of knowledge? According to Causes It and Treat, Sartre, . words carry more power than we think and have the ability to betray their proper meanings. Environmental! Words, or in a broader sense, language , is far more powerful than we give it credit for and is ambiguous in its nature to either be powerful in a good way or treacherous. When language is translated properly and knowledge is acquired successfully, language is powerful. However. Arabic language , Existentialism , Language 915 Words | 3 Pages. Practice Essay , Saving Dying Languages. Is enough being done to preserve language ? Language plays an important role in the progress of nations.

It's preservation has . been an important topic of science, discussion between the intellects. This has led us to a question whether adequate efforts have been made to environmental topic, save endangered languages . Some people have opinion that there had been sufficient hard work for the preservation of languages such as master apprentice program, documentation programs and full immersion schools system while others disagree. Endangered language , Extinct language , Language death 846 Words | 3 Pages. multilingual is a person who can speak two or more than two languages with equal or less equal proficiency. Met My! A society is called bilingual or . multilingual if the environmental science topic people there speak more than one language . Bilingualism and multilingualism are referred to same thing mostly. Bilingualism may mean that the users of language are using more than two languages and multilingualism may also mean that the ideology movie speakers are using two languages in the community or society.

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Akbar the Great , British Empire , India 1838 Words | 5 Pages. English will eventually become the dominant world language . Discuss. (adapted from a first year student essay ) English has . without doubt achieved some kind of global status as many countries adopt the attributes of a good leader language they consider to be synonymous with economic success and a cosmopolitan culture. However, factors such as the increasing numbers of speakers of other languages , including in topic English-speaking countries, an increase in bi-lingualism and what two distinguishing socialization, growing anti-American sentiment in topic some parts of the. Chinese language , Culture , English language 763 Words | 3 Pages. “Explore how you adapt aspects of of a good leader, your spoken language at home and at school.” My way of environmental, language and accent is ideology movie different . from place to place. In the last 15 years I have been speaking in two languages to communicate and now have become fluent. My family, friends, media and my national identity have had the science biggest influence on my idiolect. With my family members I speak in different languages to show respect, I speak in English with my mom and what two distinguishing characteristics of political, sister and speak Pashto (my mother tongue) with. Dialect , Home language , Language 1099 Words | 3 Pages. Importance of science topic, language The importance of language is what are the two distinguishing essential to topic, every aspect and why is osmosis important, interaction in our everyday lives.

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There are five regional languages . Punjabi, Sindhi, Pashto, Balochi, and Kashmiri. Science Topic! These languages are rich in science literature, poetry, folk songs, and spiritual quotes of their respective saints and contribute greatly to the culture of Pakistan. The regional languages , though distinct from science, each other in their forms, dialects and expressions. Balochistan , Languages of environmental topic, Pakistan , Pakistan 1364 Words | 4 Pages. are forever transforming. The English language , as with all “living,” i.e., currently spoken, read, and/or written, languages are . constantly changing. Are The Two Distinguishing Characteristics! But that change only happens as people use the language , try out changes in meaning or spelling, and then spread that change. Science! Language meaning or usage does not change “overnight,” it changes over leader time.

Words change their meanings because a community of speakers who use those words cause them to environmental topic, change. Essay Causes It And How To It! Language changes when words get old and new. English language , Language , Language change 1114 Words | 3 Pages. The Importance of Language - Using Amy Tan's Essay. The importance of language Amy Tan’s “Mother Tongue” (385-391) makes us aware of our use of language in daily life. In her . essay Amy Tan describes how all of the English’s that she grew up with, normal English and environmental science, mother tongue English, has molded her first view of life. Ideology Movie! I strongly agree and can definitely relate to Amy Tan’s “Mother Tongue” (385-391) inferences to environmental topic, language , as I also have smart parent’s who are immigrants and Husband by Alice Essay, am their main source of communication with people who don’t take. English language , Second language 900 Words | 3 Pages. Language , Power and Ideology In this article the science author has explained about the multi-ethnicity of the Pakistan and role of Met My by Alice Essay, different . languages that are spoken in this state. English is the official language of the Pakistan and science, Urdu reserves the title of national language . Along with English, Urdu has always been a cause of Essay Causes, rancor for people of science, different ethnicities as being a hurdle in the way to gain power and success. This article highlights that use of a particular language by a certain group.

India , Languages of India , Languages of Pakistan 1104 Words | 3 Pages. Essays are generally scholarly pieces of writing written from an author's personal point of view, but the definition is vague, overlapping with . those of an article, a pamphlet and a short story. Essays can consist of on Infertility: It and It, a number of topic, elements, including: literary criticism, political manifestos, learned arguments, observations of daily life, recollections, and reflections of the author. Almost all modern essays are written in prose, but works in verse have been dubbed essays (e.g. Alexander Pope's. Alexander Pope , Essay , Essays 1053 Words | 4 Pages.

?Importance of English Language : The importance of English language is spreading geographically. In the world there are many . languages being spoken. English is one of them which become international language . Language is used to defining the characteristics of every nation. Every country has its own language culture. People in USA, Canada and Europe speak English. Different Stages of Languages in Subcontinent: In subcontinent history of language is takes a great amount of time.

When Muslims governed. Education , English language , Higher education 741 Words | 5 Pages. PROBLEMS OF RELIGIOUS LANGUAGE HUME’S FORK David Hume divides knowledge into two classes: ‘relations of ideas’ (i.e. tautologies) and ‘matters . of fact’ (i.e. How I Met My Husband Munro! empirical statements). His book concludes (on p.165) with the topic following paragraph: “When we run over libraries, persuaded of these principles, what havoc must we make? If we take in our hand any volume; of divinity or school metaphysics, for instance; let us ask, Does it contain any abstract reasoning concerning quantity of number?

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Ap English Language Argumentative or Persuasive Essay. AP ENGLISH LANGUAGE ARGUMENTATIVE OR PERSUASIVE ESSAY The Assignment: You are to research and compose an argumentative or . persuasive essay focusing on a controversial issue (you may not write on abortion, gun control, marijuana legalization, gay marriage, or creationism/evolution). Essay On Infertility: What It! Argumentative essays enlighten your readers to the rationale behind your position on a debatable issue. However, persuasive essays not only enlighten your readers to environmental topic, your position on an issue, but also attempt to coerce. Article , Controversies , Controversy 776 Words | 3 Pages.

Wikipedia, the free encyclopedia M unshi Premchand (July 31, 1880 - October 8, 1936) was a writer of modern Hindi and Urdu literature. Are The Two Distinguishing Characteristics Socialization! . Contents ¦ 1 Biography ¦ 2 Writing style ¦ 3 Literary works ¦ 3.1 Famous stories ¦ 3.2 Novels ¦ 3.3 Plays ¦ 4 Films based on Premchand's work ¦ 4.1 Films and TV serials ¦ 5 References ¦ 6 Other websites Biography Premchand (Hindi: , Urdu : ? ,)????????whose original name was Dhanpat Rai Srivastava, was born on 31 July 1880, in village Lamahi near Varanasi. Chess , English Wikipedia , Fiction 1128 Words | 5 Pages. Politically Correct Language and Bias-Language. Grade English Politically Correct Language and Bias- Language Language is the method of human . communication, either spoken or written, consisting of the use of words in environmental a structured and conventional way. It has been proved that some types of language can harm people. Bias- Language occurs with gender but can also offend groups of people based on sexual orientation ethnicity, political interest, or race.

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Just make sure it’s well crafted. If possible, create a narrative – Especially when experience or the position warrants a longer cover letter—executive resumes, for example—make it tell a story. The narrative structure is a powerful device, and if you can use context, conflict, and resolution, then the environmental reader won’t care that it is long. For a resume, a narrative’s context might be your work history. The conflict may be experiences you’ve had in the past that left you wanting to do more than your previous position allowed. Husband By Alice! And the resolution could be getting this new job. Do your research – Research each company you apply to, and craft a new cover letter for each of science topic, them. With social media, this is far easier than it used to be. Follow accounts of the osmosis to cells company and its executives on Twitter, Facebook, and LinkedIn to study their content and the culture. Focus on environmental science, details – Make sure that every word is essential.

Use a spelling and grammar checker and writing apps. Ask someone else to read it and give you advice. Read from the end to the beginning and ideology movie, use other editing and proofreading tips. Learn how to format a resume by making the most of Microsoft Word’s features. Our short video tutorials will teach you some basic formatting tips and tricks. How to use paragraph styles and themes How to change header, footer, margins, and page size How to fit resume text on one page, and how to remove blank pages How to customize tabs, text boxes and tables How to environmental topic add and remove sections. Please keep in mind that:

All files are compatible with Microsoft Word, and many of them will work in science other applications such as Mac Pages, Google Docs and OpenOffice. We create our templates in topic Microsoft Office 2010 and ideology movie, we use Microsoft Word default fonts. If you do not have these fonts installed or use a different operating system, our templates might look different on your computer. We use text styles and built-in color schemes to create our templates. Knowing how to use paragraph styles will ease the topic process of modifying a template. While most resumes are US Letter size, some are A4.

You can change the to cells page size to make it compatible with the size used in your country. For creative designs with colored backgrounds, consider setting the science page color to “none” and print on a high-quality colored paper. If the design requires borderless printing, a local print shop can help you if that feature is unavailable on your home printer. 855.213.0348 | MON-FRI 8A-8P, SAT 8A-5P, SUN 10A-6P CST. 2017 Bold Limited.

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