1,720,991 research outputs found
Static and dynamic properties of liquid crystals
No full textThis work is concerned primarily with the effects of molecular flexibility on liquid crystalline properties. In particular, the role of alkyl chains in determining static and dynamic properties of liquid crystals is investigated. Theories for the orientational ordering and thermodynamic properties of flexible liquid crystals are presented. Predictions of the theories are compared with experimental results for members of the bis- 4,4'-(cyanobiphenyloxy) alkane (BCBO-n) homologous series. Order parameters for different segments in the molecules are calculated and compared with experimental values obtained by deuterium N.M.R. spectroscopy. Theoretical and experimental values for the nematic-isotropic transition temperatures, entropies of transition and order parameters at the transition are compared. The properties of dimeric liquid crystals such as the BCBO-n compounds bear a strong resemblance to those of some liquid crystalline polymers. Similarities and differences between the dimeric and polymeric liquid crystals are interpreted in terms of their respective conformational distributions. A theory is developed to account for the effects of alkyl chains on the pretransitional behaviour of nematogens. The theory is used to predict the variation of the divergence temperature, T*, with chain length for homologous series of monomeric and dimeric liquid crystals. Finally, an investigation is made of the dynamic properties of nematic liquid crystals. A theory is developed to account for the site dependence of the spin-lattice relaxation times and spectral densities measured by N.M.R. spectroscopy. The theory, which explicitly allows for internal as well as external modes, is tested by comparison with experimental results obtained for members of the alkyl- and alkoxy- cyanobiphenyl series of compounds. (D73645/87)</p
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
Non-lytic Clearance of Influenza B Virus as a Host Defense Mechanism
No full textInfluenza viruses cause acute respiratory disease, infecting 3-5 million people and causing 290-660,000 deaths annually. The vast majority of human disease is caused by influenza A and B viruses which first infect epithelial cells in the upper respiratory tract and then can spread to neighboring tissue depending on the severity of disease. Traditionally it’s been thought that tissue damage resulting from influenza disease was due to an entirely cytolytic viral infection, in which every infected cell was killed either through viral replication or immune-mediated mechanisms. Previous work from our lab and others have demonstrated, however, that cells are able to survive direct infection with apparently cytopathic viruses and that some cells can intrinsically clear the virus and persist in the host long-term. The work in this thesis focuses on the cellular response to influenza B virus infection, with an emphasis on the upper respiratory tract as the primary presentation of viral disease in seasonal influenza infections.Influenza B viruses (IBVs) are major contributors to total human influenza disease, responsible for ~1/3 of all infections. While it has historically been assumed that the viral biology and mechanisms of pathogenesis for all influenza viruses were highly similar, studies have shown that IBVs possess unique characteristics that affect how they interact with the host cell. Therefore, to determine if any cells can survive direct IBV infection, we generated a recombinant IBV capable of activating a host-cell reporter topermanently label all infected cells. In chapter one, using this system, we demonstrate that IBV infection leads to the formation of a survivor cell population in the proximal airways that are ciliated-like, but transcriptionally altered from uninfected ciliated cells in the same lung. This is the first report of cells surviving direct infection with influenza B virus and provides the basis for the work done in subsequent chapters of this thesis.In chapter two, we build on this work to demonstrate that transcriptionally altered survivor cells are phenotypically distinct from both actively infected and bystander ciliated cells. To further understand the contribution of these survivor cells to lung function during and following infection, we used depletion assays to test lung barrier function, leakiness and overall morbidity in animals with and without survivor cells. In this work we demonstrate that survivor cells are critical to maintain respiratory barrier function. These results highlight a host response pathway that preserves the epithelium to limit the severity of IBV disease.Lastly, we wanted to understand how influenza infection affects the heterogeneous upper respiratory tract tissue. Our studies demonstrated that both respiratory and olfactory epithelial cells were infected by IBV and demonstrated divergent antiviral profiles over the course of infection. As a result, the olfactory sensory neurons were able to non-lytically clear viral protein more rapidly than respiratory epithelial cells. This is, to our knowledge, the first report of infection and non-lytic clearance of a seasonal strain of IBV in the olfactory epithelium. Overall, these results demonstrate a heterogeneity in cell-intrinsic antiviral responses that contribute to differences in cellular outcomes of infection.</p
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
Viral- and host-targeted interventions to improve influenza disease outcomes
No full textDespite decades of work by scientists and public health officials, influenza viruses continue to cause widespread morbidity and mortality. Each year it is estimated that these pathogens infect up to 20% of the global population, leading to nearly a million deaths. In considering this, it is clear that additional research and intervention strategies are needed. When examining influenza virus infection and subsequent outcomes, it is easiest to look at the disease from two perspective; the virus and the host. The influenza virus, a sort of obligate intracellular parasite, must coopt a myriad of host cell proteins and processes in order to complete its lifecycle, and produce infectious progeny virions in hopes of spreading to and infecting new cells and hosts. At the same time, the infected host must both detect this viral invader, as well as mount an effective response, in the form of both innate and adaptive immune pathways, to try and limit and eventually clear the viral pathogen. In considering how important these two sides of the same coin were, we decided to take a two-pronged approach and focus our research efforts on both the virus and host in the hopes of improving influenza infection outcomes.Seasonal vaccination has been, and still remains, the best strategy for preventing influenza infection. Each year, a new formulation of the seasonal influenza vaccine is designed and manufactured with the hopes of inducing protective immunity, in the form of neutralizing antibodies, against the major circulating influenza strains. Seasonal vaccine efficacy (VE), however, remains low; averaging close to fifty percent over the past two decades. Recent work has demonstrated that this is in large part due to adaptive mutations that occur during growth of the virus in embryonated chicken eggs, the major manufacturing platform in which most vaccine doses are made, due to conformational differences between eggs and the human respiratory tract in the influenza host cell receptor, sialic acid. Many of these mutations, which often occur in the major antigenic protein hemagglutinin (HA), have been shown to drastically reduce the antigenic match to circulating strains, leading to vaccination with misrepresentative antigens. In order to combat this, we took advantage of influenza based reverse-genetic systems to design a vaccine platform resistant to these mutations. In order to combat this, we utilized reverse genetics to develop an influenza virus capable of expressing two hemagglutinins, termed a Dual-HA virus. These Dual-HA viruses encode a “helper HA” that is adapted to growth in embryonated chicken eggs, alongside the HA from a clinically relevant circulating strain. Together, we demonstrated that the Dual-HA design allows for the virus to successfully grow to high titers using the “helper HA” while simultaneously stabilizing the antigenicity of the clinically relevant HA for vaccination, theoretically preventing future adaptive mutations and enhancing seasonal vaccine efficacy.While seasonal vaccination is the best strategy for preventing influenza infections, effective therapeutics will always be needed to treat those who eventually contract the virus. To date, there have been several classes of effective antivirals that have been developed, FDA-approved and are currently used to treat infected patients. All classes of these drugs, unfortunately, elicit their effect by directly targeting influenza proteins and preventing their function. While effective in the short-term, this strategy of directly targeting viral proteins is especially risky when considering the rate at which these viruses mutate and their potential to develop resistance. Amantadines for example, the first-class of influenza antivirals developed, are no longer used in the clinic due to nearly 100% of influenza strains now possessing resistant mutations. In fact, influenza strains have been isolated possessing resistant mutations to every class of influenza antivirals we possess, highlighting the need for a more universal strategy that would be theoretically very difficult to for influenza viruses to adapt to. Once again we turned to the virus and used reverse genetics to target one of the most universally conserved processes of the influenza lifecycle, genomic segment packaging. In order to produce infectious progeny virions, influenza viruses must package their genomic segments into budding virions using conserved motifs in these segments termed packaging signals. Taking advantage of this, we engineered an influenza virus that packages and propagates two additional genomic segments missing key viral proteins termed “decoy segments”. We demonstrated that these “decoy segments” can be packaged by wild-type influenza viruses during coinfection, and that this is capable of not only interfering with replication and spread of a variety of viruses but is also capable of rescuing animals from a lethal infection when administered therapeutically. Given the near universal conservation of these packaging signals, this therapeutic strategy should be effective against a wide-range of influenza viruses, as well as be near impossible for viruses to develop resistant mutations to.Having addressed issues with both vaccination and therapeutic strategies, we next turned to looking at the host immune response during influenza infection. During the early period of infection, it is appreciated that innate immune signaling, in particular type I IFN signaling, is primarily responsible for response to and control of influenza virus infections. Interestingly, it is well appreciated that pregnant women are up to four times more likely to develop severe influenza infections. This finding become even more important when considering recent work has demonstrated that severe infections lead to systemic type I IFN signaling, and that this form of IFN signaling leads to fetal malformations and even fetal demise. Despite these findings, however, influenza infections have never been shown to significantly increase the risk of fetal demise or birth defects. Taken together, this suggests that some unidentified regulator of type I IFN signaling must be protecting the developing fetus from this harmful systemic IFN response during severe influenza infections. Using CRISPR/Cas9 screening techniques, and a type I IFN reporter system, we identified G-protein coupled estrogen receptor 1 (GPER1) as a candidate regulator. Our subsequent experiments demonstrated that blocking GPER1 function with a selective antagonist lead to prolonged IFN signaling, whereas activation with a selective agonist was capable of suppressing signaling. Furthermore, using a murine pregnancy model, we demonstrated that the loss of GPER1 function lead to drastic increase in fetal demise during influenza infection, and that GPER1 function was dispensable if maternal IFN signaling was blocked. This work suggests that GPER1 is a critical regulator of type I IFN signaling, and that modulating its function could be used to toggle innate immune responses to potentially improve infection outcomes.Taken together, these studies describe new technologies and findings that could be used to improve influenza infection outcomes. By focusing our efforts on both the virus and the host we have covered an array of areas relevant to human health including vaccination, antiviral therapeutics, and regulation of potentially dangerous host immune responses.</p
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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