1,720,959 research outputs found
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
Mutated neo-antigens as targets for individualized cancer immunotherapy
Get PDFCarcinogenesis is largely driven by somatic gene mutations. Accumulating evidence suggests that a significant subset of mutations result in neo-epitopes recognized by tumor-specific T cells and thus may constitute the Achilles' heel of malignant cells. T cells directed against mutations have been shown to have a key role in spontaneous immune responses against cancer and in the clinical efficacy of potent cancer immunotherapy modalities, such as adoptive transfer of autologous tumor infiltrating lymphocytes and immune checkpoint inhibitors. Whereas these findings strengthen the idea of a prominent role of neo-epitopes in tumor rejection, the systematic therapeutic exploitation of mutations was hampered until recently by the uniqueness of the repertoire of mutations (“the mutanome”) in every patient’s tumor. Our group pioneered to set up a process for an individualized immunotherapy approach to target the full spectrum of a patient’s personal tumor-specific mutations by combination of exome and transcriptome sequencing, bioinformatic target identification and selection followed by RNA based tumor vaccination.
In this thesis, it was shown that tumor mutations, in particular single nucleotide variations (SNVs), insertions, deletions (indels) and gene fusions are frequently immunogenic. Moreover, it was demonstrated for the first time that SNVs are predominantly recognized by CD4+ T cells. Neo-epitopes can be targeted by customized RNA-based monotope or poly-neo-epitope vaccines with substantial therapeutic effects in mouse tumor models. Notably, CD4 neo-epitope vaccination was shown to positively affect the tumor microenvironment of the CT26 colon carcinoma by decreasing the ratio of FoxP3+ regulatory T cells to CD4+ T cells and augmenting CD4+ and CD8+ T-cell infiltration. In addition, anti-tumoral efficacy of neo-epitope specific CD4+ T cells in CT26 colon carcinoma tumors was shown to critically depend on CD8+ T cells and CD40L signaling. CD40-CD40L interaction between activated CD4+ T cells and dendritic cells (DCs) mediates the upregulation of costimulatory molecules on DCs which in turn supports the priming of naive, tumor specific CD8+ T cells. A meta-analysis revealed that immunogenic SNVs and indels have a significantly better binding prediction for MHC class II than their non-immunogenic counterparts. Vaccination against mutations selected for favorable MHC class II binding prediction and abundant mutated mRNA expression resulted in tumor-control without prior immunogenicity testing.
The preclinical data shown here for three different mouse tumor models established the feasibility of individualized cancer vaccines and raised hopes that this concept will be effective in humans as well. This study paved the way and directly influenced the design of clinical studies in melanoma and triple-negative breast cancer patients.Somatische Genmutationen sind eine Hauptursache der Karzinogenese. Darüber hinaus häufen sich Hinweise, dass eine signifikanter Anteil von Mutationen zu Neo-Epitopen führen, die von tumorspezifischen T-Zellen erkannt werden und daher die Achillesferse maligner Zellen darstellen könnten. Mutationsspezifische T-Zellen spielen eine Schlüsselrolle in der spontanen Immunantwort gegen Krebs und in der klinischen Wirksamkeit erfolgreicher Immuntherapien wie dem adoptiven Transfer von tumorinfiltrierenden T-Zellen oder Immun-Checkpoint-Inhibitoren. Obgleich diese Erkenntnisse die Idee einer prominenten Rolle von Neo-Epitopen in der Abstoßung von Tumoren stärken, war eine therapeutische Nutzung bis vor kurzem durch die Einzigartigkeit des Mutatiosrepertoires (“Mutanom”) in jedem individuellen Tumor eingeschränkt. Unsere Gruppe konnte erstmals einen Prozess für eine individualisierte Immuntherapie etablieren, der das volle Spektrum tumorspezifischer Mutationen eines jeden Patienten adressiert. Mittels Exom- und Transkriptom-Sequenzierung sowie bioinformatischer Mutationsidentifizierung und Selektion wird das Mutanom eines Patienten bestimmt und durch eine RNA basierte Impfung targetiert.
Diese Arbeit zeigt, dass Tumormutationen, insbesondere einzelnukleotid Variationen (SNVs), Insertionen, Deletionen (Indels) und Genfusionen häufig immunogen sind. Zudem wird zum ersten mal demonstriert, dass SNVs hauptsächlich von CD4+ T-Zellen erkannt werden. Neo-Epitope können durch eine maßgeschneiderte RNA-basierte Monotop- oder Poly-Neo-Epitop-Vakzine adressiert werden, die einen bedeutenden therapeutischen Effekt in murinen Tumoren hervorruft. Es konnte gezeigt werden, dass eine CD4 Neo-Epitop-Vakzinierung das Tumormikromilieu des CT26 Kolonkarzinoms durch Reduzierung des Verhältnisses von suppressiven FoxP3+ regulatorischen T-Zellen zu CD4+ T-Zellen und durch Steigerung der CD4+ und CD8+ T-Zellinfiltration positiv beeinflusst. Zudem wurde gezeigt, dass der antitumorale Effekt mutationsspezifischer CD4+ T-Zellen entscheidend von CD8+ T-Zellen und CD40L Signalisierung abhängt. Der CD40-CD40L Singalweg zwischen aktivierten CD4+ T-Zellen und dendritischen Zellen (DCs) führt zur Hochregulierung kostimulatorische Moleküle auf DCs das wiederum das Priming naiver, tumorspezifischer CD8+ T-Zellen fördert. Eine Metaanalyse konnte zeigen, dass immunogene im Vergleich zu nicht-immunogenen SNVs sowie Indels eine signifikant bessere Bindungsvorhersage für MHC-Klasse-II haben. Vakzinierung gegen Mutationen mit prädizierter MHC-Klasse-II Bindung sowie hoher Expression von mutierter mRNA im Tumor führte zu einem antitumoralem Effekt ohne einer vorherigen Immunogenitätstestung.
Die hier gezeigten präklinischen Studien in drei verschiedenen Maus-Tumormodellen beweißen die Durchführbarkeit einer individualisierten Krebsvakzine und wecken Hoffnungen, dass dieses Konzept ebenfalls bei Menschen erfolgreich sein wird. Diese arbeit bereitete den Weg und beeinflusste das Design von klinischen Studien in Melanom- und dreifach negativen Brustkrebspatienten.95 Blätte
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
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
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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