1,721,054 research outputs found
The role of nerve growth factor and p75 neurotrophin receptor in recovery from liver fibrosis
No full textRodent hepatic myofibroblasts are susceptible to nerve growth factor-mediated apoptosis through p75 neurotrophin receptor ligation. Hepatic myofibroblast apoptosis is critical to resolution of liver fibrosis. I show that human hepatic myofibroblasts exhibit differential responses to mature and pro-nerve growth factor/p75 neurotrophin receptor-mediated signals. Whilst mature nerve growth factor is proapoptotic, pronerve growth factor protects human hepatic myofibroblasts from serum-deprivation and cycloheximide-induced apoptosis. To define the dominant effect of p75 neurotrophin receptor-mediated events in experimental liver fibrosis I have used a mouse lacking the p75 neurotrophin receptor ligand-binding domain but expressing the intracellular domain. I show that absence of p75 neurotrophin receptor ligand-mediated signals leads to significantly retarded architectural resolution and reduced hepatic myofibroblast loss by apoptosis. Lack of the ligand-competent p75 neurotrophin receptor limits hepatocyte proliferative capacity in vivo without preventing hepatic stellate cell transdifferentiation. Moreover, in recovery from experimental liver fibrosis the fall in pro-nerve growth factor mirrors loss of hepatic myofibroblasts by apoptosis. Thus, nerve growth factor species have a differential effect on hepatic myofibroblast survival, and p75 neurotrophin receptor ligand-mediated events facilitate reduction of liver fibrosis via regulation of hepatic myofibroblast proliferation and apoptosis, and hepatocyte proliferation
Powers scaling and nonlinear frequency conversion of single-frequency lasers based
No full textThis thesis presents a strategy for power-scaling diode-end-pumped solid-state lasers based on Nd:YLF operating on the 1.053 µm line whilst retaining, efficient, single-frequency, diffraction limited output, the characteristics of low power operation. This strategy reduces the effects of energy transfer up-conversion (ETU), which can decrease the lifetime of the upper lasing level and increase the heat generated per unit volume within the laser rod, increasing the effects of detrimental thermally related problems such as thermal lensing, stress-induced birefringence and stress induced laser rod fracture. Also a passive technique for mode-hopping-suppression is described, allowing the oscillating frequency within the laser cavity to tune over many axial mode spacings before a mode-hop occurs. In order to de-couple the problems of laser resonator power scaling from the maintenance of robust and reliable single-frequency operation, the Nd:YLF laser oscillator output is amplified via Nd:YLF based amplifier stages. A model is presented of the effects of ETU on thermal lensing and small signal gain within the amplifiers along with projected results for further power-scaling prospects. In order to increase the frequency tuning capabilities of the master-oscillator-power-amplifier (MOPA), it was used to pump a series of cw singly-resonant optical parametric oscillators (SROs) based on periodically-poled lithium niobate. Although SROs are inherently single-frequency they suffer detrimentally from mode-hopping, therefore in the final stages of this thesis, we propose to utilise the novel passive technique for mode-hopping-suppression with the SRO cavities in order to achieve robust and reliable single-frequency output. Theoretical expressions and design strategy for low SRO threshold and efficient slope efficiency are expressed along with detailed analysis of the mode-hopping nature of their output. Preliminary results for cw SROs are presented and details of SRO mode-hopping-suppression are included
Whole slide images of armadillo liver from M.leprae dataset
No full textWhole slide images of H&E stained sections of liver from nine-banded armadillos chronically systemically infected by Mycobacterium leprae, resistant to systemic infection by Mycobacterium leprae, or uninfected. Images acquired on a Hamamatsu NanoZoomer in .ndpi format.Provided in Readme.txt
DNA fusion gene vaccination mobilizes effective anti-leukemic cytotoxic T lymphocytes from a tolerized repertoire
No full textThe majority of known human tumor-associated antigens derive from non-mutated self proteins. T cell tolerance, essential to prevent autoimmunity, must therefore be cautiously circumvented to generate cytotoxic T cell responses against these targets. Our strategy uses DNA fusion vaccines to activate high levels of peptide-specific CTL. Key foreign sequences from tetanus toxin activate tolerance-breaking CD4+ T cell help. Candidate MHC class Ibinding tumor peptide sequences are fused to the C terminus for optimal processing and presentation. To model performance against a leukemia-associated antigen in a tolerized setting, we constructed a fusion vaccine encoding an immunodominant CTL epitopederived from Friend murine leukemia virus gag protein (FMuLVgag) and vaccinated tolerant FMuLVgag-transgenic (gag-Tg) mice. Vaccination with the construct induced epitopespecificIFN-c-producing CD8+ T cells in normal and gag-Tg mice. The frequency and avidity of activated cells were reduced in gag-Tg mice, and no autoimmune injury resulted. However, these CD8+ T cells did exhibit gag-specific cytotoxicity in vitro and in vivo. Also, epitope-specific CTL killed FBL-3 leukemia cells expressing endogenous FMuLVgag antigen and protected against leukemia challenge in vivo. These results demonstrate a simple strategy to engage anti-microbial T cell help to activate epitope-specific polyclonal CD8+ T cell responses from a residual tolerized repertoire
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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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