1,721,037 research outputs found
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
Vaccine-Induced Antibody and Cellular Correlates and Anti-Correlates of Risk of SIV/HIV Acquisition
No full textPh.D.RV144 is the only phase III HIV vaccine clinical trial that has demonstrated a statistically significant reduced risk of HIV acquisition (31.2%). In this study, the primary correlate of reduced risk was IgG targeting the V2 loop at the apex of the trimeric envelope spike protein and mediating antibody-dependent cellular cytotoxicity. The SIVmac251 macaque challenge model has served as a rigorous tool to test RV144-derived HIV vaccine candidates and study the immune correlates of risk. The first question in this dissertation addressed whether passive immunization with monoclonal antibodies targeting the V2 loop could directly reduce the risk of SIV acquisition in naïve macaques. We addressed this question mechanistically with the two IgG1 monoclonal antibodies NCI05 and NCI09, in an IgG1 format, recognizing the coil/helical or the β-strand conformation of the V2 epitope, respectively. NCI05 outperforms NCI09 in antibody-dependent cellular cytotoxicity whereas NCI09 outperforms NCI05 in antibody-dependent cellular phagocytosis and trogocytosis. This study revealed that the mucosal level of NCI05 strongly correlated with delayed mucosal acquisition of SIV, suggesting that the coil/helical epitope of V2 is a virus vulnerability site. Thereafter, we developed a V1-deleted (ΔV1 gp120) vaccine platform to focus the antibody response to the α-helix of V2. The encouraging results in macaques with the V1-deleted immunogens have led to a Phase I clinical trial with these immunogens at the NCI. The second part of this dissertation explored whether we could develop a plasmid DNA vaccine platform to simplify the vaccine regimen. We compared our efficacious DNA/ALVAC/ΔV1gp120/Alum5mg vaccine platform with DNA/ΔV1gp120/Alum0.85mg DNA/ΔV1gp120/ALFQA0.85mg regimens. We subsequently tested a double protein boosted regimen with higher alum content DNA/2xΔV1gp120/2xAlum5mg to increase vaccine efficacy. The studies revealed that the components of the DNA vaccine platform in the absence of ALVAC elicit a protracted IFN-γ response and T-bet+ CD4+ T-cells. These data are indicative of a polarization of cellular immunity to inflammatory M1 macrophages and TH1 cells correlated with an increased risk of acquisition. These studies revealed that ALVAC is an essential component of our candidate HIV vaccine regimen through the elicitation of balanced TH1/TH2 responses, efferocytosis, and decreased tissue recruitment of activated T-cells
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
Identification of novel monocistronic HTLV-1 mRNAs encoding functional Rex isoforms
Full text linkBackground: Human T cell leukemia virus type 1 (HTLV-1) gene expression is controlled by the key regulatory proteins Tax and Rex. The concerted action of these proteins results in a two-phase kinetics of viral expression that depends on a time delay between their action. However, it is difficult to explain this delay, as Tax and Rex are produced from the same mRNA. In the present study we investigated whether HTLV-1 may produce novel mRNA species capable of expressing Rex and Tax independently. Findings: Results revealed the expression of three alternatively spliced transcripts coding for novel Rex isoforms in infected cell lines and in primary samples from infected patients. One mRNA coded for a Tax isoform and a Rex isoform, and two mRNAs coded for Rex isoforms but not Tax. Functional assays showed that these Rex isoforms exhibit activity comparable to canonic Rex. An analysis of the temporal expression of these transcripts upon ex vivo culture of cells from infected patients and cell lines transfected with a molecular clone of HTLV-1 revealed early expression of the dicistronic tax/rex mRNAs followed by the monocistronic mRNAs coding for Rex isoforms. Conclusion: The production of monocistronic HTLV-1 mRNAs encoding Rex isoforms with comparable activity to canonical Rex, but with distinct timing, would support a prolonged duration of Rex function with gradual loss of Tax, and is consistent with the two-phase expression kinetics. A thorough understanding of these regulatory circuits will shed light on the basis of viral latency and provide groundwork to develop strategies for eradicating persistent infections
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
Human T-Lymphotrophic virus type 1 (HTLV-1) infection of the three monocyte subsets in HAM/TSP patients
No full textHuman T- Lymphotropic virus type 1 (HTLV-1) is an exogenous retrovirus that establishes a persistent infection in humans. HTLV-1 is the causative agent of two distinct pathologies: adult T-cell Leukemia/Lymphoma (ATLL), an aggressive malignancy of mature CD4+ T cells, and HTLV-1-associated myelopathy/tropic spastic paraparesis (HAM/TSP), a demyelinating neurodegenerative disease. An estimated 15-20 million of people worldwide with endemic regions in Japan, equatorial Africa, the Caribbean and SouthAmerica are infected with HTLV-1. While the majority of HTLV-1 infected individuals remain asymptomatic, a low percentage of patients develop either ATLL (2-3%) or HAM/TSP (2-3%) after a long period of clinical latency.
HTLV-1 primarly infects CD4+ T cells and has been detected in ex vivo CD8+ T cells, B cells, monocytes and dendritic cells (DC) from infected individuals. Although the major target of HTLV-1 is CD4+ lymphocytes, the virus has been shown to infect monocytes both in vitro and in vivo. Thus, monocytes represent a putative reservoir for the virus. Peripheral blood monocytes can be classified into three main subsets: CD14++CD16–(classical),CD14+CD16++(non-classical), and CD14++CD16+(intermediate) which exert important roles in innate and adaptive immunity. However, the contribution of the individual monocyte subsets to HTLV-1 disease and viral persistence has not been addressed.
Because viral DNA burden correlates with disease development, we investigated the contribution of monocyte subsets (classical, intermediate and non-classical) to the total viral burden in 22 HTLV-1 infected individuals by assessing their infectivity status, frequency, as well as chemotactic and phagocytic functions.
The three monocyte subsets sorted from HTLV-1 infected individuals were all positive for viral DNA and the frequency of classical monocytes in blood was lower while expression levels of the chemokine receptors CCR5, CXCR3 and CX3CR1 was higher; the percentage of intermediate monocytes and their chemokine receptor expression did not differ.
However, the migratory capacity of intermediate monocytes to CCL5, the ligand for CCR5, was higher and there was a higher proportion of non-classical monocytes that expressed CCR1, CXCR3 and CX3CR1. The level of viral DNA in the monocyte subsets correlated with the migration capacity to CCL2, CCL5 and CX3CL1 for classical monocytes, with lower phagocytosis for intermediate monocytes, and with the level of viral DNA in CD8+ and CD4+ T-cells for non-classical monocytes. These data suggest a model whereby
HTLV-1 infection augments the number of classical monocytes that migrate to tissues and become infected and the number of infected non-classical monocytes that transmit virus to CD4+ and CD8+ T-cells. These results, together with prior findings in a macaque model of HTLV-1 infection, support the notion that infection of monocytes by HTLV-1 is likely a requisite for viral persistence in humans.
Importance
Monocytes have been implicated in immune regulation and disease progression in patients with HTLV-1-associated inflammatory diseases. We detected HTLV-1 viral DNA in all three monocyte subsets and found that infection impacts surface receptor expression, migratory function and subset frequency. The frequency of non-classical patrolling monocytes is increased in HTLV-1-infected individuals and they have increased expression of CCR1, CXCR3 and CX3CR1. Viral DNA level in non-classical monocytes correlated with viral DNA level in CD4+ and CD8+ T-cells. Altogether, these data suggest an increased recruitment of classical monocytes to inflammation sites that may result in virus acquisition and, in turn, facilitates virus dissemination and viral persistence. Our findings thus provide new insight into the importance of monocyte infection in viral spread and suggest targeting monocytes for therapeutic intervention
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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