1,720,988 research outputs found
Surface expression of alien hybrid IE/C antigens on the reticulum cell sarcoma of SJL/J mice
No full textSerological demonstration of an allogeneic Ia.7 antigen on the cell surface of SJL/J-derived reticulum cell sarcomas
No full textThe reticulum cell sarcomas (RCS) of SJL/J mice are of particular interest since they readily induce the proliferation of syngeneic T-lymphocytes. Previous cellular studies examined the antigens on the RCS which stimulated this response and suggested that the tumor expressed allogeneic I-region-associated (Ia) antigens normally associated with the E alpha:E beta molecular complex (S. M. Wilbur and B. J. Bonavida, Exp. Med., 153: 501-513, 1981). These particular Ia glycoproteins are not expressed on normal SJL/J cells due to a defect in the E alpha polypeptide synthetic pathway. However, the E beta subunit is synthesized normally by these animals but remains intracellular. The SJL/J-derived RCS may circumvent this defect in E alpha subunit biosynthesis. The aberrant synthesis of this polypeptide is thought to allow membrane presentation of an intact pseudoallogeneic Ia glycoprotein which utilized the normally dormant E beta s polypeptide. In the present study, two monoclonal antibodies directed against the Ia.7 specificity of the E alpha chain (13/18, 14-4-4S) were used to examine more directly the expression of this polypeptide on the tumor. Surprisingly, neither antibody was effective against the RCS in a direct complement-mediated cytolysis assay. Nevertheless, the tumor was found to specifically adsorb lytic activity of both the monoclonal antibodies. In addition, both a cold-cell competition assay and indirect immunofluorescence corroborated the data and indicated that the RCS does express detectable levels of the Ia.7 antigen. Normal spleen cells and lipopolysaccharide B-derived blasts from SJL/J mice were found in all experiments to be devoid of any specific reactivity with these monoclonal antibodies. In addition, continued in vivo passage of transplantable RCS was found to cause down-modulation of the Ia.7 specificities on these tumors. Newer RCS transplantable lines, however, expressed demonstrable levels of this alloantigen in both cellular and serological assays. The observed down-modulation could explain the difficulties encountered in defining this specificity on long-term transplantable RCS. In conclusion, the present serological study corroborates the early cell-binding data. An Ia.7 antigen is shown to be expressed on the RCS, yet this specificity could not be detected on normal SJL/J cells
Chapter 11: The role of nitric oxide on vascular dysfunction during aging and Alzheimer’s disease.
No full textNitric oxide (NO) is an endogenously synthesized free radical involved in a plethora of physiological phenomena affecting cardiovascular homeostasis and neural functions. Its unregulated bioavailability has been recognized as a key factor in neurodegenerative disorders, especially in relation to the mechanisms through which NO-mediated vascular impairment accentuates the effect of reactive oxygen species. Interestingly, the recent literature indicates the pivotal role of NO and oxidative stress to both early and advanced stages of neurodegenerative disorders, as well as promoting their progression. Alzheimer’s disease (AD) is the most common form of dementia, characterized by extracellular amyloid (Aβ) plaques and intracellular neurofibrillary tangles coupled with reactive microgliosis and the loss of neurons and synapses in the cortex. However, the recent research supports the hypothesis of the pivotal role of NO depletion in the reduction of extracranial blood flow and impairment of cortical and peripheral circulation with a consequent detriment of cognitive function in humans with AD. It is worth of mention that AD, the leading form of dementia, continues to elude the scientific “armada” devoted on fighting this disruptive neurodegenerative disease, particularly with respect to its multifaceted origin. Although research on the biological mechanisms underlying the cause and the progression of AD is advancing, we are far to discover effective therapeutics or disease-modifying approaches. Currently, there is no absolute cure for AD: the few drugs available simply lessen the clinical symptoms. Therefore, new therapeutic approaches, including NO homeostasis, should be considered and might be useful as therapeutic targets
Preclinical models to assess the pharmacological properties of NO derivatives
No full textThe field of pharmacology of nitric oxide (NO) has various clinical perspectives as cardiovascular and metabolic disorders, neurovascular and neurodegenerative diseases, muscular–skeletal disorders, ocular, respiratory, and a large series of inflammation-related pathologies, and, on top of these, infective and neoplastic diseases. Depending on the pathology and pathophysiological mechanisms, different pharmacological approaches can be developed and used, either to stimulate NO synthases (NOS), improve NO availability and activate downstream NO-related pathways or, on the opposite, to downregulate NOS, scavenge NO, and inhibit NO-related signaling.
In either conditions, preclinical tools and models are needed to allow molecule or therapeutic strategy screening, evaluating the relative potency, efficacy, and safety in a reliable, simple, relatively cheap, and not time-consuming manner.
Different models have been developed during time, starting from the classic isolated organs maintained in balanced buffers and measuring their typical functional responses as relaxation/contraction. The introduction of cell cultures, genetic manipulation, and molecular studies has allowed to go in deep detail on the cellular and molecular mechanisms controlling upstream and downstream NO signaling. The chapter will present the cell types and cellular models (2D and 3D) available to study functional aspects of NO related strategies as well as the control of cell–cell interaction. By using selective biochemical inhibitors of signaling pathways, the involvement of intracellular messengers can be assessed and verified in functional responses both on cell cultures and in isolated organs. Finally, animal models reproducing human diseases or their symptoms can be used to assess the efficacy of synthetic strategies, NO delivery systems, and potential drugs or drug combinations in controlling pathology progression or in inducing disorder regression. Efficacy studies on experimental models, together with safety assessment, indeed allow to obtain predictive information for the proper design of safe human clinical trials
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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