1,720,960 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
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
The role of neuropilin 2 in physiological and pathological angiogenesis and lymphangiogenesis
Get PDFThe generation of new lymphatic vessels through lymphangiogenesis has been implicated in many disease states. This process has some overlap with the better studied angiogenesis pathway, but is under distinct molecular control. Specifically, it has been shown that VEGFR-3 and neuropilin-2 are important mediators of lymphangiogenesis. A greater understanding of this process could lead to new therapies for cancer and lymphedemas. We investigated lymphatic vessel growth in a mouse model with a focus on the effects of neuropilin-2 knockout. First, we induced an immunogenic response via delayed-type hypersensitivity to examine lymphangiogenesis in the physiologic state. Our neuropilin-2 knockout mouse model displayed a decreased ability to resolve inflammation on exposure to an allergen. Next, we subcutaneously injected a highly invasive melanoma to examine lymphangiogenesis in the pathologic state. We noted significantly reduced tumor growth in our neuropilin-2 knockout. In addition, the neuropilin-2 knockout mice displayed reduced vessel area in comparison to their wild-type littermates, suggesting that inhibition of neuropilin-2 may prove a potent antitumor therapeutic strategy. These results highlight neuropilin-2's important role as a mediator of physiological and pathological angiogenesis and lymphangiogenesis
Identification of CLK2 and CLK4 as novel regulators of DNA damage-induced NF-κB activity by chemical dissection
Get PDFChemotherapy and radiation are standard-of-care cancer treatments, but their effectiveness is often hampered by therapy resistance within the tumor. Numerous studies have demonstrated that tumor cells can evade cell death triggered by genotoxic therapies by activating IKK/NF-κB pathway, thereby preventing apoptosis. The direct targeting of IKKs using pharmacological interventions is not a viable option due to the significant adverse effects caused by the essential role of IKK/NF-κB signaling in various physiological processes. To circumvent this, previous work by our group identified structurally unrelated small molecule inhibitors, MW01 and MW05, that selectively inhibit IKK/NF-κB solely in response to DNA double strand breaks induced by chemotherapy and radiation. Importantly, these compounds do not interfere with IKK/NF-κB activation triggered by other physiological stimuli.
Initial work began by confirming the genotoxic stress-specific inhibition by the compounds before moving onto target identification studies. Considering the similar cellular effects of both compounds within the DNA damage-induced NF-κB pathway, comparative target identification studies including kinase assay panels, structural derivatization, and molecular signaling characterization were performed, seeking targets shared between both lead compounds. Common regulators shared by other NF-κB stimuli were first excluded as potential targets of the compounds before investigation of the several identified shared targets revealed a previously unknown regulators of genotoxic stress-induced NF-κB activity, Cdc-like kinases (CLK) 2 and 4, as the functional target of MW01 and MW05. Silencing of the CLK2 and 4 revealed that they are essential for DNA damage-induced NF-κB activity and promote the phosphorylation of IKK at Ser-85, a genotoxic stress specific ATM-dependent phosphosite, critically localizing the CLKs within the cascade between ATM and IKK. CLK2 and 4 were also confirmed as the target of active structural derivatives of MW01 and MW05 and were spared by inactive derivatives, confirming CLK2 and 4’s role in genotoxic stress-induced NF-κB. In addition, CLK inhibitor MU-1210 also inhibited NF-κB following DNA damage, suggesting that CLK inhibitors could be used to potentiate the tumor killing effect of standard cancer treatments.
MW01 and MW05 were tested in co-treatment with DNA damaging agents, in the context of on-going DNA damage, and in patient derived glioblastoma cells to assess their potential clinical applications. Critically, neither MW01 nor MW05 exhibit general toxicity; instead, they notably enhance apoptosis specifically in tumor cells following genotoxic stress. In BRCA1-deficient cells and in co-treatment with PARP inhibitor Olaparib, both characterized by on-going DNA damage, MW01 and MW05 potentiated DNA damage and p53 levels, suggesting that the compounds unbalance the NF-κB/p53 axis in favor of apoptosis. This approach introduces a novel therapeutic strategy to curb NF-κB activity induced by DNA damage in cancer cells without impacting its essential functions in healthy cells.Chemotherapie und Bestrahlung gehören zu den Standard-Krebstherapien, ihre Wirksamkeit wird jedoch häufig durch das Auftreten von Therapieresistenzen im Tumor beeinträchtigt. Zahlreiche Studien haben gezeigt, dass Tumorzellen dem durch genotoxische Therapien ausgelösten Zelltod entgehen können, indem sie den IKK/NF-κB-Signalweg aktivieren und so die Apoptose verhindern. Das direkte Angreifen von IKKs durch pharmakologische Interventionen ist keine praktikable Option, da die wesentliche Rolle der IKK/NF-κB-Signalübertragung bei verschiedenen physiologischen Prozessen erhebliche negative Auswirkungen erwarten lässt. Um dies zu umgehen, hat unsere Gruppe strukturell nicht verwandte niedermolekulare Inhibitoren, MW01 und MW05, identifiziert, die die einzigartige Fähigkeit besitzen, die Aktivierung von IKK/NF-κB ausschließlich als Reaktion auf durch Chemotherapie und Bestrahlung verursachte DNA-Doppelstrangbrüche selektiv zu hemmen. Wichtig ist, dass diese Verbindungen die durch andere normale physiologische Reize ausgelöste IKK/NF-κB-Aktivierung nicht beeinträchtigen.
Die ersten Arbeiten begannen mit der Bestätigung der genotoxischen Stress-spezifischen Hemmung durch die Verbindungen, bevor die Studien zur Identifizierung der Targets fortgesetzt wurden. In Anbetracht der ähnlichen zellulären Wirkungen beider Verbindungen innerhalb des durch DNA-Schäden induzierten NF-κB-Stoffwechsels wurden vergleichende Studien zur Identifizierung von Zielmolekülen durchgeführt, einschließlich Kinase-Assay-Panels, struktureller Derivatisierung und molekularer Signalcharakterisierung, um gemeinsame Zielmoleküle der beiden Leitverbindungen zu finden. Gemeinsame Regulatoren anderer NF-κB-Stimuli wurden zunächst als potenzielle Ziel-Proteine der Verbindungen ausgeschlossen, bevor die Untersuchung der verschiedenen identifizierten gemeinsamen Ziel-Enzyme einen bisher unbekannten Regulator der durch genotoxischen Stress induzierten NF-κB-Aktivität, die Cdc-ähnlichen Kinasen 2 und 4 (CLK2 und 4), als funktionelles Ziel von MW01 und MW05 ergab. CLK2 und 4 wurden auch als Ziel-Kinasen aktiver Strukturderivate von MW01 und MW05 bestätigt und blieben von inaktiven Derivaten verschont, was die Rolle von CLK2 und 4 bei der durch genotoxischen Stress induzierten NF-κB bestätigt. Darüber hinaus hemmte ein externer, strukturell unähnlicher CLK-Inhibitor, MU-1210, ebenfalls NF- κB nach DNA-Schäden, was darauf hindeutet, dass CLK-Inhibitoren zur Verstärkung der tumortötenden Wirkung von Standard-Krebstherapien eingesetzt werden könnten.
Parallel zu den Studien zur Identifizierung der Zielmoleküle wurden MW01 und MW05 auch bei der gleichzeitigen Behandlung mit DNA-schädigenden Substanzen, im Zusammenhang mit laufenden DNA-Schäden und in Glioblastomzellen von Patienten getestet, um ihre potenziellen klinischen Anwendungen zu bewerten. Kritisch anzumerken ist, dass weder MW01 noch MW05 eine allgemeine Toxizität aufweisen; stattdessen verstärken sie insbesondere die Apoptose in Tumorzellen nach genotoxischem Stress. In BRCA1-defizienten Zellen und bei gleichzeitiger Behandlung mit dem PARP-Inhibitor Olaparib, die beide durch anhaltende DNA-Schäden gekennzeichnet sind, verstärkten MW01 und MW05 den γH2AX-Wert, einen Marker für DNA-Schäden, und den p53-Wert, was darauf hindeutet, dass die Verbindungen die NF-κB/p53-Achse zugunsten der Apoptose aus dem Gleichgewicht bringen. Dieser Ansatz stellt eine neuartige therapeutische Strategie dar, um die durch DNA-Schäden in Krebszellen induzierte NF-κB-Aktivität zu bremsen, ohne ihre wesentlichen Funktionen in gesunden Zellen zu beeinträchtigen
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
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