1,720,955 research outputs found
Protective Immune Response Against H1N1 Influenza Challenge in BALB/c Mice Vaccinated with Liposomes Containing Adjuvants and No Influenza Protein
No full textIntroduction: Commercial influenza vaccines depend upon stimulation of the adaptive immune response to viral proteins that mutate year to year. We have been investigating a liposomal vaccine containing only adjuvants to stimulate an innate immune response against influenza which does not require activation of the adaptive immune response directed against influenza proteins. Methods: Previously, we found that a protective innate immune response in BALB/c mice against H1N1 influenza was generated by a comaleimide (CMI) liposomal vaccine (VesiVax®,Molecular Express Inc.) containing the TLR2 agonist, Pam3CAG (25ug/day) (L-Pam3CAG) administered intranasally (IN) d-4 and d-2 before viral challenge. In this study, we altered the vaccine regimen to determine the effects of timing and adjuvant dose on protection, administering liposomes IN (25ug Pam3CAG/day) d-4/-2, d-2, d-4 or d-4(PBS) to BALB/c mice [10 mice/group (gp)]. D0 mice were challenged IN with 10XLD50 H1N1 and monitored for morbidity 2X/day to d28. Results: Survival was significantly better for mice given L-Pam3CAG d-4/-2 (50%, p=0.01) or d-4 (40%, (p≤0.05).) versus PBS mice (0%); d-2 dosing produced only 10% survival. Disease signs paralleled survival with L-Pam3CAG on d-4/-2 or d-4 producing significantly lower disease scores compared to the d-2 and PBS groups (p≤0.04). Conclusions: Given that the d-4/-2 and d-4 regimens yielded the best survival while d-2 dosing gave poor survival, the timing of administration of the L-Pam3CAG appeared to be more important than the dose of Pam3CAG for stimulating an effective innate immune response to influenza challenge.Oral Presentatio
PTEN and the Regulation of Macrophage Antimicrobial Effector Functions
No full textMacrophage effector functions include ingestion and killing of microbes, along with induction, maintenance, and chronicity of the inflammatory response. Understanding the host-derived mechanisms that enhance phagocyte antimicrobial effector function is critical for creating treatments to clear the infection. We and others have shown that lipid and protein phosphatase and tensin homolog (PTEN) reduces microbial ingestion and killing during fungal infection in macrophages. In the current work, we found that macrophage PTEN inhibits Methicillin-resistant Staphylococcus aureus (MRSA) phagocytosis in macrophages. PTEN effects are accompanied by reduced gene and protein expression of the scavenger receptors (SRs) MARCO and CD36, hindering receptor-mediated phagocytosis during MRSA infections. We next investigated the killing capacity of macrophages deficient in PTEN and observed enhanced killing compared to control macrophages. To investigate the mechanism of this increase in killing, we measured the pH of these cells and observed increased acidity in the PTEN deficient macrophages. We then investigated the role of PTEN in human phagocytes, using PBMC-derived monocytes from a PTEN haploinsufficient patient and healthy controls. CyTOF analysis showed that certain immune subsets, but not all, were reduced in the patient, highlighting the role for PTEN in the homeostasis of specific monocyte subsets. RNA sequencing analysis gave us further insights into the programming of these cells. Patient monocytes displayed defects in phagosome, lysosome, and innate immune pathways. These results suggest that human and murine PTEN is an important inhibitor of multiple processes during phagocyte effector functions against MRSA infection
Protective Immune Response Generated Against Influenza Challenge In Mice Vaccinated With Liposomes Containing Different Adjuvants And No Proteins
No full textSeveral commercial influenza vaccines stimulate an adaptive immune response to yearly mutating influenza proteins. We have investigated a liposomal vaccine containing only adjuvant molecules and no proteins to stimulate an innate immune response for protection against influenza infection. In Study 1 different doses of a liposomal VesiVax® vaccine (Molecular Express Inc.) containing the adjuvant Pam3CAG, were used to vaccinate mice (n=9/group) and included: intranasal (IN) d4, d2 pre-challenge; subcutaneous (SC) d2 pre-challenge; IN d2, d4 post-challenge; SC d2 post challenge; SC buffer d2 pre-challenge. Mice were challenged d0 IN with influenza and monitored for morbidity 2X/day to d21. In Study 2 using the optimized regimen from Study 1 (IN d4, d2 pre-challenge), we examined the protection produced by different adjuvants incorporated into the liposomes. These adjuvants included Pam3CAG, cyclic dinucleotide (CDN), and mycoviral dsRNA; liposomes with no adjuvant or buffer were used as controls. In Study 1, using the Pam3CAG liposomes, the dosing regimen that was significantly better than all other groups (89% survival) was the IN d4 and d2 pre-challenge (p ≤ 0.0006). In Study 2, survival was higher for the Pam3CAG liposomes (67% survival) compared to the liposomes containing CDN (p=0.03) or buffer control (p=0.06). Weight loss and disease signs paralleled survival
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
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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