10,824 research outputs found
Detection of autoreactive T cells in H-2(u) mice using peptide-MHC multimers
No full textMyelin basic protein (MBP)-specific T cells play a critical role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a prototype for T cell-mediated autoimmunity. In PL/J and B10.PL mice (H-2(u) haplotype), the immunodominant epitope of MBP is represented by an N-terminal nonameric peptide, MBP1-9. To date, the MBP1-9-specific T cell repertoire has not been analyzed in quantitative terms. In the present study we demonstrate, using MHC class II tetramers, that 15,000-70,000 self-antigen-specific T(h) cells accumulate in the draining lymph nodes following immunization with spinal cord homogenate or MBP1-9. In contrast, MBP1-9-specific T cells are undetectable in unimmunized H-2(u) mice and represent >60% of the CD4 cells in naive mice transgenic for a TCR specific for this epitope. The results suggest that the extremely low affinity of the N-terminal peptide for I-A(u) does not limit the MBP1-9-specific T cells from expanding into a sizeable pool of autoreactive T cells. Therefore, the primary immune response to MBP1-9 does not differ quantitatively from previously reported CD4+ T cell responses to foreign antigens.</p
Panel C: Author-Meets-Readers Session
No full textAuthor David Webber discusses his book The Rise of the Working Class Shareholder: Labor\u27s Last Best Weapon published on Harvard University Press
Cult: A Composite Novel
No full textCult (redacted)
The first component of the thesis is a composite novel called Cult which falls into two parts with seven narratives in each. Part 1 tracks the protagonist, Ellen, from her first involvement with the cult through to her eventually leaving it. Although fiction, the first half of the book answers the kinds of questions the author is asked when people discover that she was once a sannyasin (a follower of the guru Bhagwan Shree Rajneesh). While the experiences of meditation, group therapy and communal living are all faithfully rendered within the stories, the need for strong characters, narrative drive and a lightness of touch takes precedence.
Part 2 picks up Ellen’s story some twenty or so years later and explores what becomes of her in middle age. It also looks at other groups in society, such as academia, the law and the internet dating community which each have their own jargon, hierarchies, rituals and rules but are not considered to be cults.
The book examines the question raised in the Epigraph, ‘how do we be together when we feel so alone’ with a focus on relationships other than the familial and the romantic.
Collisions, Chasms and Connections: a Performative Exploration of the Composite Novel Form
The second part of the thesis is both a critical and creative response to three contemporary American books: Olive Kitteridge by Elizabeth Strout; A Visit from the Goon Squad by Jennifer Egan; and Legend of a Suicide by David Vann. The critical element comprises a close reading of the three books; a chronological reconstruction of their overarching storylines; and a consideration of what their authors have said about writing the books. It concludes that, in the composite novel, the simultaneous presentation of multiple views and storylines operate much like a 3D image to give the impression of depth to the characters and situations rendered. The creative element of the essay is a playful and personal response to the texts
Analysis of a File System Using the Verifying C Compiler
No full textTitle: Analysis of a File System Using the Verifying C Compiler Author: Bc. David Škorvaga Department: Department of Distributed and Dependable Systems Supervisor: RNDr. Jan Kofroň, Ph.D. Abstract: Formal verification is a way to improve reliability of software systems. One approach of formal verification is focused on proving correctness of annotat- ed source code of an established programming language. Verifying C Compiler (VCC) is a verifier for concurrent C that accepts an annotated code in C language and automatically verifies its correctness with respect to the given annotation. There have been successful attempts to verify some critical systems, including the operating system kernel. Another critical part of operating system is its file system. In the thesis, we choose FatFs file system, a simple device-independent implementation of the FAT file system. We specify a part of it using the VCC annotation and successfully verify its correctness. Keywords: Formal Verification, File System, VC
Analýza souborového systému pomocí Verifying C Compiler
No full textNázev práce: Analýza souborového systému pomocí Verifying C Compiler Autor: Bc. David Škorvaga Katedra: Katedra distribuovaných a spolehlivých systémů Vedoucí diplomové práce: RNDr. Jan Kofroň, Ph.D. Abstrakt: Formální verifikace je jeden ze způsobů, jak zlepšit spolehlivost soft- warových systémů. Jeden z přístupů formální verifikace se zaměřuje na dokazo- vaní správnosti anotovaného zdrojového kódu v široce používaném programovacím jazyce. Verifier C Compiler (VCC) je verifikátor pro concurrent C, který přijímá anotovaný kód v jazyce C a automaticky ověřuje jeho správnost s ohledem na tuto anotaci. Už se objevily úspěšné pokusy o ověření některých kritických systémů, včetně jádra operačního systému. Další důležitou součástí operačního systému je jeho systém souborů. V diplomové práci jsme si vybrali souborový systém FatFs, odlehčenou implementaci souborového systému FAT, nezávislou na zařízení. V této práci vytvoříme specifikaci jeho části pomocí anotace VCC a úspěšně ověříme jeho korektnost. Klíčová slova: Formal Verification, File System, VCCTitle: Analysis of a File System Using the Verifying C Compiler Author: Bc. David Škorvaga Department: Department of Distributed and Dependable Systems Supervisor: RNDr. Jan Kofroň, Ph.D. Abstract: Formal verification is a way to improve reliability of software systems. One approach of formal verification is focused on proving correctness of annotat- ed source code of an established programming language. Verifying C Compiler (VCC) is a verifier for concurrent C that accepts an annotated code in C language and automatically verifies its correctness with respect to the given annotation. There have been successful attempts to verify some critical systems, including the operating system kernel. Another critical part of operating system is its file system. In the thesis, we choose FatFs file system, a simple device-independent implementation of the FAT file system. We specify a part of it using the VCC annotation and successfully verify its correctness. Keywords: Formal Verification, File System, VCCDepartment of Distributed and Dependable SystemsKatedra distribuovaných a spolehlivých systémůMatematicko-fyzikální fakultaFaculty of Mathematics and Physic
Protein Free Energy Landscapes Remodeled by Ligand Binding
No full textAbstractGlucose/galactose binding protein (GGBP) functions in two different larger systems of proteins used by enteric bacteria for molecular recognition and signaling. Here we report on the thermodynamics of conformational equilibrium distributions of GGBP. Three fluorescence components appear at zero glucose concentration and systematically transition to three components at high glucose concentration. Fluorescence anisotropy correlations, fluorescent lifetimes, thermodynamics, computational structure minimization, and literature work were used to assign the three components as open, closed, and twisted conformations of the protein. The existence of three states at all glucose concentrations indicates that the protein continuously fluctuates about its conformational state space via thermally driven state transitions; glucose biases the populations by reorganizing the free energy profile. These results and their implications are discussed in terms of the two types of specific and nonspecific interactions GGBP has with cytoplasmic membrane proteins
El Tlacuache Núm. 498 (2011). 498 Año 11 (2011) diciembre. El Tlacuache
No full textChalcatzingo: Breve introducción por David C. Grov
Negative selection during the peripheral immune response to antigen
No full textThymic selection depends on positive and negative selective mechanisms based on the avidity of T cell interaction with antigen-major histocompatibility Complex complexes. However, peripheral mechanisms for the recruitment and clonal expansion of the responding T cell repertoire remain obscure. Here we provide evidence for an avidity-based model of peripheral T cell clonal expansion in response to antigenic challenge. We have used the encephalitogenic, H-2 Au-restricted, acetylated NH2-terminal nonameric peptide (Ac1-9) epitope from myelin basic protein as our model antigen. Peptide analogues were generated that varied in antigenic strength (as assessed by in vitro assay) based on differences in their binding affinity for Au. In vivo, these analogues elicited distinct repertoires of T cells that displayed marked differences in antigen sensitivity. Immunization with the weakest (wild-type) antigen expanded the high affinity T cells required to induce encephalomyelitis. In contrast, immunization with strongly antigenic analogues led to the elimination of T cells bearing high affinity T cell receptors by apoptosis, thereby preventing disease development. Moreover, the T cell repertoire was consistently tuned to respond to the immunizing antigen with the same activation threshold. This tuning mechanism provides a peripheral control against the expansion of autoreactive T cells and has implications for immunotherapy and vaccine design.</p
Long-term follow-up of endurance and safety outcomes during enzyme replacement therapy for mucopolysaccharidosis VI: Final results of three clinical studies of recombinant human N-acetylgalactosamine 4-sulfatase
No full textCopyright © 2008 Elsevier Inc. All rights reserved.UnlabelledThe objective of this study was to evaluate the long-term clinical benefits and safety of recombinant human arylsulfatase B (rhASB) treatment of mucopolysaccharidosis type VI (MPS VI: Maroteaux-Lamy syndrome), a lysosomal storage disease. Fifty-six patients derived from 3 clinical studies were followed in open-label extension studies for a total period of 97-260 Weeks. All patients received weekly infusions of rhASB at 1 mg/kg. Efficacy was evaluated by (1) distance walked in a 12-minute walk test (12MWT) or 6-minute walk test (6MWT), (2) stairs climbed in the 3-minute stair climb (3MSC), and (3) reduction in urinary glycosaminoglycans (GAG). Safety was evaluated by compliance, adverse event (AE) reporting and adherence to treatment.ResultsA significant reduction in urinary GAG (71-79%) was sustained. For the 12MWT, subjects in Phase 2 showed improvement of 255+/-191 m (mean+/-SD) at Week 144; those in Phase 3 Extension demonstrated improvement from study baseline of 183+/-26 m (mean+/- SE) in the rhASB/rhASB group at Week 96 and from treatment baseline (Week 24) of 117+/-25 m in the placebo/rhASB group. The Phase 1/2 6MWT and the 3MSC from Phase 2 and 3 also showed sustained improvements through the final study measurements. Compliance was 98% overall. Only 560 of 4121 reported AEs (14%) were related to treatment with only 10 of 560 (2%) described as severe.ConclusionrhASB treatment up to 5 years results in sustained improvements in endurance and has an acceptable safety profile.Paul Harmatz, Roberto Giugliani, Ida Vanessa D. Schwartz, Nathalie Guffon, Elisa Leão Teles, M. Clara Sá Miranda, J. Edmond Wraith, Michael Beck, Laila Arash, Maurizio Scarpa, David Ketteridge, John J. Hopwood, Barbara Plecko, Robert Steiner, Chester B. Whitley, Paige Kaplan, Zi-Fan Yu, Stuart J. Swiedler, Celeste Decker and for the MPS VI Study Grouphttp://www.elsevier.com/wps/find/journaldescription.cws_home/622920/description#descriptio
‘They remain just bodies’: on pornography in David Foster Wallace (1989–2006)
No full textDavid Foster Wallace was deeply involved in a tricky and vexed research on pornography from 1989, as the recurrence of this theme in several non-fiction essays, brief stories, novels, interviews, and archival documents makes clear. The analysis of pornography in Wallace’s oeuvre offers the opportunity both to further explore his commitment to other fundamental topics – such as the overlap between addiction and entertainment – and to understand the significance of this theme in his overall literary project. Thus, employing a chronological approach, the chapter focuses on some published writings and unpublished documents in the period which runs from 1989 to 2006. The chapter argues that Wallace mobilized the paradox of pornography – which he understood as the erotic engagement of the viewers and the denial of any form of relationship among viewers and performers – in order to show that there was another way to experience intimacy through an aesthetic practice, namely the act of reading which, as he often stressed, is characterized by a distinctive and powerful conversation between author and reader
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