1,720,988 research outputs found
Hypophysitis Secondary to Cytotoxic T-Lymphocyte-Associated Protein 4 Blockade: Insights into Pathogenesis from an Autopsy Series
No full textHypophysitis that develops in cancer patients treated with monoclonal antibodies blocking cytotoxic T-lymphocyte-associated protein 4 (CTLA-4; an inhibitory molecule classically expressed on T cells) is now reported at an incidence of approximately 10%. Its pathogenesis is unknown, in part because no pathological examination of the pituitary gland has been reported to date. We analyzed at autopsy the pituitary glands of six cancer patients treated with CTLA-4 blockade, one with clinical and pathological evidence of hypophysitis, one with mild lymphocytic infiltration in the pituitary gland but no clinical signs of hypophysitis, and four with normal pituitary structure and function. CTLA-4 antigen was expressed by pituitary endocrine cells in all patients but at different levels. The highest levels were found in the patient who had clinical and pathological evidence of severe hypophysitis. This high pituitary CTLA-4 expression was associated with T-cell infiltration and IgG-dependent complement fixation and phagocytosis, immune reactions that induced an extensive destruction of the adenohypophyseal architecture. Pituitary CTLA-4 expression was confirmed in a validation group of 37 surgical pituitary adenomas and 11 normal pituitary glands. The study suggests that administration of CTLA-4 blocking antibodies to patients who express high levels of CTLA-4 antigen in the pituitary can cause an aggressive (necrotizing) form of hypophysitis through type IV (T-cell dependent) and type II (IgG dependent) immune mechanisms
DEVELOPING AND APPLYING SEQUENCING-BASED TOOLS TO UNDERSTAND ADAPTIVE IMMUNE RESPONSES IN MYOSITIS
No full textIdiopathic inflammatory myopathies (IIMs) are a group of heterogeneous, systemic diseases characterized by skeletal muscle pathologies, which most commonly result in chronic, progressive muscle weakness. Immune infiltrates, which includes B and T cells, are often found in the muscle of IIM patients. Currently, autoantibodies help stratify IIMs into clinical subtypes, however disease heterogeneity persists within subtypes of IIMs and the etiologies of IIMs remain unknown. Through the application of adaptive immune profiling methods: 1) Phage Immunoprecipitation Sequencing (PhIP-Seq) to understand antibody reactivities at cohort-scale and 2) B cell receptor sequencing, I have further characterized the antibody repertoires in IIMs. Using PhIP-Seq, I identified novel environmental and autoantibody reactivities in subtypes of IIMs. These findings may generate hypotheses about IIM etiologies, and improve IIM disease classifications. Using both PhIP-Seq and BCR sequencing, I characterized the diversity of the local antibody repertoire in muscle tissue of IIM patients, improving our understanding of the adaptive immune response within muscle. To improve our ability to perform immune receptor repertoire sequencing in a low-cost, high-throughput manner, I developed a method, INtraCEllular Reverse Transcription with Sorting and sequencing, or INCERTS, to efficiently link T cell phenotypes with T cell receptor sequencies. INCERTS is complementary to single-cell sequencing. Through the application of these sequencing- based methods, I have increased our understanding of the B cell immune response in IIMs. Through the development of INCERTS, I have improved our ability to perform immune receptor repertoire sequencing, which can be applied to further increase our understanding of the adaptive immune response in IIMs
DEVELOPING AND APPLYING SEQUENCING-BASED TOOLS TO UNDERSTAND ADAPTIVE IMMUNE RESPONSES IN MYOSITIS
No full textIdiopathic inflammatory myopathies (IIMs) are a group of heterogeneous, systemic diseases characterized by skeletal muscle pathologies, which most commonly result in chronic, progressive muscle weakness. Immune infiltrates, which includes B and T cells, are often found in the muscle of IIM patients. Currently, autoantibodies help stratify IIMs into clinical subtypes, however disease heterogeneity persists within subtypes of IIMs and the etiologies of IIMs remain unknown. Through the application of adaptive immune profiling methods: 1) Phage Immunoprecipitation Sequencing (PhIP-Seq) to understand antibody reactivities at cohort-scale and 2) B cell receptor sequencing, I have further characterized the antibody repertoires in IIMs. Using PhIP-Seq, I identified novel environmental and autoantibody reactivities in subtypes of IIMs. These findings may generate hypotheses about IIM etiologies, and improve IIM disease classifications. Using both PhIP-Seq and BCR sequencing, I characterized the diversity of the local antibody repertoire in muscle tissue of IIM patients, improving our understanding of the adaptive immune response within muscle. To improve our ability to perform immune receptor repertoire sequencing in a low-cost, high-throughput manner, I developed a method, INtraCEllular Reverse Transcription with Sorting and sequencing, or INCERTS, to efficiently link T cell phenotypes with T cell receptor sequencies. INCERTS is complementary to single-cell sequencing. Through the application of these sequencing- based methods, I have increased our understanding of the B cell immune response in IIMs. Through the development of INCERTS, I have improved our ability to perform immune receptor repertoire sequencing, which can be applied to further increase our understanding of the adaptive immune response in IIMs
Visualizing MIPSA: Exploring Web-based User Experience Design in Teaching and Promoting Molecular Technology
Full text linkThis thesis explores the potential of web-based user experience in teaching and promoting a novel molecular technology, Molecular Indexing of Proteins by Self Assembly (MIPSA), which is a scalable and low-cost solution for comprehensive antibody profiling. Despite its potential applications, there are no existing visuals that explain the complex science of MIPSA. To address this gap, a website was developed with animations, graphics, and concise content to educate and engage the target audience of researchers and investors in biotechnology.
The website is the first of its kind to explain and visualize the concept of MIPSA using multimedia and the multimedia learning theory. The website aims to deliver the didactic content in an engaging and comprehensible way by employing website design principles, multimedia and the multimedia learning theory. A focus group was held with researchers and students at Johns Hopkins to assess the effectiveness of the website, and results showed high ratings for overall effectiveness, navigation, content organization, and visual appeal. The project's implications for biocommunication and the promotion of a new molecular technology are discussed, along with suggestions for future studies
Visualizing MIPSA: Exploring Web-based User Experience Design in Teaching and Promoting Molecular Technology
No full textThis thesis explores the potential of web-based user experience in teaching and promoting a novel molecular technology, Molecular Indexing of Proteins by Self Assembly (MIPSA), which is a scalable and low-cost solution for comprehensive antibody profiling. Despite its potential applications, there are no existing visuals that explain the complex science of MIPSA. To address this gap, a website was developed with animations, graphics, and concise content to educate and engage the target audience of researchers and investors in biotechnology.
The website is the first of its kind to explain and visualize the concept of MIPSA using multimedia and the multimedia learning theory. The website aims to deliver the didactic content in an engaging and comprehensible way by employing website design principles, multimedia and the multimedia learning theory. A focus group was held with researchers and students at Johns Hopkins to assess the effectiveness of the website, and results showed high ratings for overall effectiveness, navigation, content organization, and visual appeal. The project's implications for biocommunication and the promotion of a new molecular technology are discussed, along with suggestions for future studies
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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