130,546 research outputs found
Identification of protective antigens for vaccination against systemic salmonellosis
No full textThere is an urgent medical need for improved vaccines with broad serovar coverage and high efficacy against systemic salmonellosis. Subunit vaccines offer excellent safety profiles but require identification of protective antigens, which remains a challenging task. Here, I review crucial properties of Salmonella antigens that might help to narrow down the number of potential candidates from more than 4000 proteins encoded in Salmonella genomes, to a more manageable number of 50-200 most promising antigens. I also discuss complementary approaches for antigen identification and potential limitations of current pre-clinical vaccine testing
Target identification for prevention and therapy of "Salmonella" infections
No full textIn this thesis we investigated maintenance requirements of Salmonella during chronic infections, and determined the relevant antigen properties that might facilitate the development of Salmonella vaccines. Overall, we wanted to achieve two goals:
a)To identify suitable targets to eradicate persisting Salmonella.
b)Identify antigen properties for developing enteric fever vaccine.
To achieve the first goal we established a practical Salmonella mouse infection model for identifying bacterial maintenance functions essential for persistency.Using this model, we evaluated twelve Salmonella defects. Our data revealed extremely relaxed environment of Salmonella during persistency compared to the acute infection. On the other hand, we identified that unsatuarated/ cyclopropane fatty acid synthesis pathway might contain suitable targets for antimicrobial chemotherapy of chronic infections.
To achieve the second goal, we tested thirty seven in vivo expressed antigens for immunogenicity and protectivity in a mouse typhoid fever model. We identified novel Salmonella antigens that conferred partial protection against virulent Salmonella in a typhoid fever model. The identified antigens had high sequence conservation among several Salmonella serovars suggesting that these antigens might be suitable as vaccine candidates against systemic Salmonella infection caused by diverse serovars. Using model antigens expressed in Salmonella and autologous antigens, our data also revealed that surface associated antigens might be promising for inducing both humoral and cellular immunity to Salmonella, as recognition of such antigens might enable uniquely detection and destruction of live Salmonella. This may provide a strategy to discover additional protective antigens for Salmonella and other intracellular pathogens
MeSH term explosion and author rank improve expert recommendations
No full textInformation overload is an often-cited phenomenon that reduces the productivity, efficiency and efficacy of scientists. One challenge for scientists is to find appropriate collaborators in their research. The literature describes various solutions to the problem of expertise location, but most current approaches do not appear to be very suitable for expert recommendations in biomedical research. In this study, we present the development and initial evaluation of a vector space model-based algorithm to calculate researcher similarity using four inputs: 1) MeSH terms of publications; 2) MeSH terms and author rank; 3) exploded MeSH terms; and 4) exploded MeSH terms and author rank. We developed and evaluated the algorithm using a data set of 17,525 authors and their 22,542 papers. On average, our algorithms correctly predicted 2.5 of the top 5/10 coauthors of individual scientists. Exploded MeSH and author rank outperformed all other algorithms in accuracy, followed closely by MeSH and author rank. Our results show that the accuracy of MeSH term-based matching can be enhanced with other metadata such as author rank
Heterogeneity of inflammation and host metabolism in a typhoid fever model
No full textSystemic infections can lead to severe inflammation and altered host metabolism. These host responses are being extensively studied, but their spatial relationships in infected tissues remain largely unknown.
The goal of this thesis was to investigate the spatial organization of metabolic and inflammatory patterns in Salmonella-infected tissues and to elucidate the impact of host heterogeneity on host-Salmonella interactions in a murine typhoid fever model.
We showed that antimicrobial effector mechanisms such as generation of ROS and RNS occurred predominantly in granulomatous lesions. However, a substantial fraction of Salmonella resided outside of these lesions and was therefore not covered by these antimicrobial regions. Heterogeneous exposure to RNS induced distinct, locally adapting Salmonella subpopulations (see chapter 2.1).
We also investigated host metabolic enzyme activities in various tissue regions. Using a novel combination of immunostaining with enzyme histochemistry, we showed that granulomas had a distinct metabolic profile with a high capacity for generation of NADPH, an essential substrate for local generation of bacteriostatic/bactericidal ROS and RNS. Indeed, adaptation of GFP-based live/dead discrimination revealed extensive Salmonella killing that predominantly occurred in granulomas (see chapter 2.2).
The spatial segregation of live Salmonella from regions with massive killing also offered a potential explanation why surface-associated Salmonella antigens, but not internal antigens that are inaccessible in live Salmonella, were required for protective immunity (see chapter 2.3).
In conclusion, this thesis revealed markedly heterogeneous conditions in Salmonella-infected host tissues that had profound impact on disease mechanisms, infection control, and immunity
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
I rapporti di filosofia, storia e psicologia in H. Steinthal
No full textUntil now, critics have dealt with Steinthal’s work in terms of
his contributions to the Kulturwissenschaft (Bumann, Meschiari,
Trautmann-Waller), linguistics (Trabant, Ringmacher) and semantics
theory (Formigari, Knobloch). This study focuses on the
philosophy supporting his linguistic-psychological theories. Connections
established between philosophy, philology and psychology
demonstrate Steinthal’s originality in the Nineteenth-century
debate on history, his contiguity with/difference to Böckh
"Closing the R&D Gap, Evaluating the Sources of R&D Spending"
No full textBoth spending and tax policies have been implemented in the United States with the goal of stimulating private sector research and development (R&D). Karier questions whether current R&D policy, especially the research and experimentation tax credit, can contribute to closing the gap between nondefense expenditures on R&D in the United States and such expenditures in other countries, such as Japan and Germany. He also explores possible changes to our current R&D policy to make it more effective.
Dispelling the Myths Behind First-author Citation Counts
No full textWe 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
Scholarly Communication and Publishing Lunch and Learn Talk #11: The ULS Open Access Author Fee Fund
No full textAt the May 2014 talk, you will learn about the ULS Open Access Author Fee Fund--what it is, why we do it, how it works, and how the program is going so far
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