2,067 research outputs found

    Natural and engineered antibodies against HIV

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    Epigraphene : epitaxial graphene on silicon carbide

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    This article presents a review of epitaxial graphene on silicon carbide, from fabrication to properties, put in the context of other forms of graphene.Comment: 46 pages, 322 references, 35 figures. Submitted December 201

    sCD4-17b bifunctional protein: Extremely broad and potent neutralization of HIV-1 Env pseudotyped viruses from genetically diverse primary isolates

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    <p>Abstract</p> <p>Background</p> <p>We previously described a potent recombinant HIV-1 neutralizing protein, sCD4-17b, composed of soluble CD4 attached via a flexible polypeptide linker to an SCFv of the 17b human monoclonal antibody directed against the highly conserved CD4-induced bridging sheet of gp120 involved in coreceptor binding. The sCD4 moiety of the bifunctional protein binds to gp120 on free virions, thereby enabling the 17b SCFv moiety to bind and block the gp120/coreceptor interaction required for entry. The previous studies using the MAGI-CCR5 assay system indicated that sCD4-17b (in concentrated cell culture medium, or partially purified) potently neutralized several genetically diverse HIIV-1 primary isolates; however, at the concentrations tested it was ineffective against several other strains despite the conservation of binding sites for both CD4 and 17b. To address this puzzle, we designed variants of sCD4-17b with different linker lengths, and tested the neutralizing activities of the immunoaffinity purified proteins over a broader concentration range against a large number of genetically diverse HIV-1 primary isolates, using the TZM-bl Env pseudotype assay system. We also examined the sCD4-17b sensitivities of isogenic viruses generated from different producer cell types.</p> <p>Results</p> <p>We observed that immunoaffinity purified sCD4-17b effectively neutralized HIV-1 pseudotypes, including those from HIV-1 isolates previously found to be relatively insensitive in the MAGI-CCR5 assay. The potencies were equivalent for the original construct and a variant with a longer linker, as observed with both pseudotype particles and infectious virions; by contrast, a construct with a linker too short to enable simultaneous binding of the sCD4 and 17b SCFv moieties was much less effective. sCD4-17b displayed potent neutralizing activity against 100% of nearly 4 dozen HIV-1 primary isolates from diverse genetic subtypes (clades A, B, C, D, F, and circulating recombinant forms AE and AG). The neutralization breadth and potency were superior to what have been reported for the broadly neutralizing monoclonal antibodies IgG b12, 2G12, 2F5, and 4E10. The activity of sCD4-17b was found to be similar against isogenic virus particles from infectious molecular clones derived either directly from the transfected producer cell line or after a single passage through PBMCs; this contrasted with the monoclonal antibodies, which were less potent against the PMBC-passaged viruses.</p> <p>Conclusions</p> <p>The results highlight the extremely potent and broad neutralizing activity of sCD4-17b against genetically diverse HIV-1 primary isolates. The bifunctional protein has potential applications for antiviral approaches to combat HIV infection.</p

    First direct observation of a nearly ideal graphene band structure

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    Angle-resolved photoemission and X-ray diffraction experiments show that multilayer epitaxial graphene grown on the SiC(000-1) surface is a new form of carbon that is composed of effectively isolated graphene sheets. The unique rotational stacking of these films cause adjacent graphene layers to electronically decouple leading to a set of nearly independent linearly dispersing bands (Dirac cones) at the graphene K-point. Each cone corresponds to an individual macro-scale graphene sheet in a multilayer stack where AB-stacked sheets can be considered as low density faults.Comment: 5 pages, 4 figure

    Interaction of glycoprotein H of human herpesvirus 6 with the cellular receptor CD46.

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    Human herpesvirus 6 (HHV-6) employs the complement regulator CD46 (membrane cofactor protein) as a receptor for fusion and entry into target cells. Like other known herpesviruses, HHV-6 encodes multiple glycoproteins, several of which have been implicated in the entry process. In this report, we present evidence that glycoprotein H (gH) is the viral component responsible for binding to CD46. Antibodies to CD46 co-immunoprecipitated an approximately 110-kDa protein band specifically associated with HHV-6-infected cells. This protein was identified as gH by selective depletion with an anti-gH monoclonal antibody, as well as by immunoblot analysis with a rabbit hyperimmune serum directed against a gH synthetic peptide. In reciprocal experiments, a monoclonal antibody against HHV-6 gH was found to co-immunoprecipitate CD46. Studies using monoclonal antibodies directed against specific CD46 domains, as well as engineered constructs lacking defined CD46 regions, demonstrated a close correspondence between the CD46 domains involved in the interaction with gH and those previously shown to be critical for HHV-6 fusion (i.e. short consensus repeats 2 and 3)

    Large area and structured epitaxial graphene produced by confinement controlled sublimation of silicon carbide

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    After the pioneering investigations into graphene-based electronics at Georgia Tech (GT), great strides have been made developing epitaxial graphene on silicon carbide (EG) as a new electronic material. EG has not only demonstrated its potential for large scale applications, it also has become an invaluable material for fundamental two-dimensional electron gas physics showing that only EG is on route to define future graphene science. It was long known that graphene mono and multilayers grow on SiC crystals at high temperatures in ultra-high vacuum. At these temperatures, silicon sublimes from the surface and the carbon rich surface layer transforms to graphene. However the quality of the graphene produced in ultrahigh vacuum is poor due to the high sublimation rates at relatively low temperatures. The GT team developed growth methods involving encapsulating the SiC crystals in graphite enclosures, thereby sequestering the evaporated silicon and bringing growth process closer to equilibrium. In this confinement controlled sublimation (CCS) process, very high quality graphene is grown on both polar faces of the SiC crystals. Since 2003, over 50 publications used CCS grown graphene, where it is known as the "furnace grown" graphene. Graphene multilayers grown on the carbon-terminated face of SiC, using the CCS method, were shown to consist of decoupled high mobility graphene layers. The CCS method is now applied on structured silicon carbide surfaces to produce high mobility nano-patterned graphene structures thereby demonstrating that EG is a viable contender for next-generation electronics. Here we present the CCS method and demonstrate several of epitaxial graphene's outstanding properties and applications

    Work in Progress: Rigorously Assessing the Anecdotal Evidence of Increased Student Persistence in an Active, Blended, and Collaborative Mechanical Engineering Environment

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    This work in progress describes an ongoing study of an active, blended, and collaborative (ABC) course environment used in a core mechanical engineering course. This course has built on the growing body of literature citing active learning (Freeman et al., 2014), blended structures (Bowen & Ithaka, 2012), and collaborative engagement (Jeong & Chi, 2007) as positive influences on college and university science, technology, engineering, and math (STEM) outcomes. For the last six years, “Dynamics”, a core mechanical engineering course at a large public university, has utilized in-class activities, frequently-watched problem-solving videos, and a collaborative blog space to realize an ABC environment. On one key metric of course success, the rate of students who drop, fail, or withdraw from (DFW), the course has experienced near-constant improvements since the ABC structures were introduced. In this study, the authors utilize rigorous longitudinal methods to determine whether this drop in DFW rates can be directly attributed to increased implementation of ABC features. The authors hypothesize that as instructors become accustomed to the ABC environment and increase the level of in-class activity, use of blended resources, and collaboration, the likelihood of DFW in each subsequent year would drop. However, in the same time period, each subsequent class entered with higher levels of performance on proxy measures for prior knowledge. We therefore build a logistic regression model to predict individual-level DFW and determine whether the anecdotal drops in DFW that we observe can be attributed to the expansion of the ABC environment. More specifically, we predict likelihood of DFW based on students’ prior knowledge (grade in the preceding course, SAT math score), key demographics (gender, race/ethnicity), the semester and year they took Dynamics, their instructor, their year in school, and their major. We test for year fixed effects {year_t, t = 1, 2, ..., 7} to determine whether odds ratios for DFW consistently and significantly decrease over time. We also test for instructor effects, in particular for differences between the instructors who were involved in the design and development of the ABC environment and more independent instructors who only partially implemented the ABC course components. We anticipate results that will provide more rigorous, less biased, and efficient estimates for the individual- and class-level components that explain variance in DFW rates. These results would provide immediate implications for the next phase of our work, as we assess the next on-term implementation of the course in 2016. Our findings would also have long-term significance for other classes in mechanical engineering and related disciplines and for classes at other institutions that are considering implementing a comprehensive ABC learning environment

    Transforming a Dynamics Course to an Active, Blended, and Collaborative Format: Focus on the Faculty

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    Mechanical engineering programs are increasingly applying educational research by transforming courses to be more interactive and to use a blend of online and face-to-face materials. However, the process of an existing course adopting these new practices is not well studied, and even less is understood about the faculty experience from on-boarding to delivery of a new curriculum or pedagogy. In this study, we follow the translation of an active, blended, and collaborative (ABC) curriculum for a core dynamics course from a large public university (where the ABC curriculum was developed) to a small private university. We use interpretive phenomenology to focus on the lived experience of the instructor newly implementing these course materials, format, and pedagogical approach. Specifically, we address the following research questions: (1) What is the lived experience of a mechanical engineering instructor at a different institution as she adopts and adapts the provided materials and format? (2) How does the experience of this instructor evolve throughout the semester? We use rich qualitative data to understand the experience of the instructor, who taught this course in its prior format and, in Fall 2015, taught the “off-term” core dynamics course via the new ABC structure. Through weekly reflection prompts, pre- and post-semester interviews, and supplementary process data (e.g., notes of weekly meetings between the new implementer and ABC team at the large public university), we describe and characterize the multi-faceted instructor experience. This includes her experience learning about the curriculum and online tools, implementing the class and adjusting her teaching practices, and assessing her students’ engagement with the course and understanding of dynamics concepts. Our findings suggest further areas of inquiry for studies of faculty practices around curriculum adoption, including probing opportunities for cross-institutional collaborations to share materials and transform courses, interrogating variation in mechanical engineering department and student cultures, and studying sources of faculty development and support throughout the course transformation process
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