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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
The systematic use of multicolor Flow Cytometry for T cell phenotyping with critical examination of the applications and limitations
No full textDie funktionelle Beurteilung von T-Zellen ist ein wichtiges, aber bisher nur unbefriedigend gelöstes diagnostisches Problem im Umgang mit Patienten mit eingeschränkter Immunantwort. Die Entwicklung der Multicolor-Durchflusszytometrie bietet neue Möglichkeiten, T-Zell Antworten zu charakterisieren. Im Rahmen dieser Arbeit wurde die Multicolor-Durchflusszytometrie in der Arbeitsgruppe etabliert und anhand praktischer Versuche deren Anwendungsmöglichkeiten untersucht. Dabei wurde ein systematisches Konzept für die Entwicklung von Färbepanels entwickelt, mit dessen Hilfe zwei Panels (Zytokin-Panel und Memory-Panel erstellt wurden. Schließlich wurden die Anwendungsmöglichkeiten und Grenzen des Ansatzes untersucht.
Um zu gewährleisten, dass auch seltene Events zuverlässig detektiert werden können, mussten die Bedingungen des Assays optimiert werden. Als Stimulus war SEB am besten geeignet. Die Inkubationszeit sollte mindestens 5 Stunden betragen. Als optimale Stimulationsdauer zeigten sich 8.5h mit Zugabe eines Golgi-Blockers nach 2h. Die Dichte der Zellen sollte 6*106/ml nicht überschreiten, um eine optimale Antwort nicht zu schwächen. Es ist wichtig, einen Vitalfarbstoff zu verwenden, insbesondere um seltene Events zu messen. Für die intrazelluläre Anfärbung hat sich der amine reactive dye nearIR ViD als geeignet erwiesen.
Für die Auswahl eines Korrelates der Aktivierung spielen die Kinetik, Sensitivität, Spezifität und Handhabung eine Rolle. Unter den hier etablierten Bedingungen waren CD154 für CD4 T-Zellen und CD137 für CD8 T-Zellen am besten geeignet.
Für das Panel-Design ist eine sorgfältige Zuordnung der Antikörper zu den Farbstoffkanälen des Geräts wichtig. Sie erfolgte nach rationalen Kriterien wie Spillover, Fluorochrom-Intensität und Ausstattung des verwendeten Durchflusszytometers. Daraus ergab sich ein Basispanel zur Bestimmung der Haupt-Zellpopulationen, das nach den Anforderungen des aktuellen Experimentes mit Aktivierungsmarkern ergänzt werden konnte: CD56 PE-Cy7, CD4 PerCP-Cy5.5, CD3 PacificBlue und nearIR ViD. Die Kanäle für FITC, PE und Alexa647 blieben für Anpassungen frei.
Die Kompensation der Messungen nimmt eine wichtige Stellung in der Multicolor-Durchflusszytometrie ein. Um eine korrekte Kompensation zu gewährleisten, wurde jeder Antikörper nach einem systematischen Ansatz titriert. Um den Einfluss der Autofluoreszenz von Zellen auf die Kompensationseinstellungen auszuschalten, wurde die Kompensation mit an Beads gebundenen Antikörpern durchgeführt. Als Kontrolle zur Bestimmung der Positivität von Aktivierungsmarkern wurde das Prinzip der fluorescence minus one Kontrolle eingesetzt.
Die in der vorliegenden Arbeit entwickelten Panels wurden exemplarisch angewendet, um ihre Möglichkeiten und Grenzen zu untersuchen. Mit dem Zytokin-Panel konnte die Qualität von T-Zell-Antworten bestimmt werden und Einfach- bis Dreifach-Zytokinproduzenten unterschieden werden. Im T-Zell-Pool eines Normalkollektivs ergab sich eine Aufteilung 7% (triple), 24% (double) und 69% (single) unter den CD4 Zellen und 1% (triple), 28% (double) und 71% (single) unter den CD8-Zellen. Das Normalkollektiv kann als Bezugsrahmen für weitere Messungen verwendet werden. Die Qualität der Antwort spielt eine zentrale Rolle bei der Impfstoffentwicklung.
Die zunehmende Menge an verfügbaren Markern macht einen Konsensus in der Definition von T-Zell-Populationen nötig. Mit dem Memory-Panel wurden die Reifungsstadien von T-Zellen betrachtet. Dabei zeigte sich im Normalkollektiv gesunder Blutspender bei CD4-Zellen eine andere Verteilung als bei CD8-Zellen. Es ist zu definieren welche Abweichungen Krankheitswert haben könnten.
In Zusammenarbeit mit der Arbeitsgruppe Gentherapie des Instituts für Biochemie wurde die T-Zell-Antwort auf eine Tumorvakzine charakterisiert. In der Zytokinbestimmung nach 24h Inkubation zeigten sich deutliche Unterschiede hinsichtlich des Effektes, den die Transfektion unterschiedlicher Zytokine in Tumorzellen auf die Stimulation einer allogenen T-Zell-Antwort erzielten.In the evaluation of immunocompromised patients the functional assessment of T cells is an important but not yet sufficiently solved diagnostic problem. Multicolor flow cytometry offers new possibilities in the characterization of T cell responses. In the present work multicolor flow cytometry was established in the workgroup and its applications were evaluated by using practical experiments. A systematic approach for designing antibody panels was developed, resulting in two panels (cytokine panel and memory panel). Eventually potential applications and limits of this approach were studied.
To reliably detect even rare events the stimulation assay had to be optimized. SEB was the most suitable stimulating agent. Assays should be incubated for at least 5 hours. The optimal duration of stimulation was determined at 8.5 h with addition of a Golgi block after 2 h. The cell density should not exceed 6*106/mL to not weaken an optimal response. To detect rare events it is crucial to use a viability dye. For intracellular staining the amine reactive dye nearIR ViD was suitable.
For the selection of an activation marker the kinetics, sensitivity, specificity and handling have to be considered. With the assay conditions outlined above the most suitable activation markers were CD154 for CD4 T cells and CD137 for CD8 T cells.
When designing a panel a careful pairing of fluorophores to fluorescence channels of the flow cytometer has to be ensured. This was done by rational criteria like spilllover, fluorochrome intensity and equipping of the flow cytometer in use. The result is a basic panel to characterize the main cell populations with the option to expand further activation markers: CD56 PE-Cy7, CD4 PerCP-Cy5.5, CD3 PacificBlue and nearIR ViD. We spared the channels for FITC, PE and Alexa647 for adaptations.
Compensation is of utmost importance in multicolor flow cytometry. In order to minimize spillover, each antibody was titrated by a systematic approach.
To eliminate the influence of cell autofluorescence to the compensation settings, the compensation was carried out using antibodies bound to beads. As a control to determine the cut off for activation markers, the principle of fluorescence minus one was used.
The panels developed in the present work were applied exemplarily to study their applications and limitations. The cytokine panel can be used to determine the quality of T cell responses and to distinguish single, double and triple cytokine producers. In a group of healthy subjects there were 7% triple, 24% double and 69% single cytokine producers within the CD4 cells and 1% triple, 28% double and 69% single producers in the CD8 cells. This group can be used as a norm group for further experiments. The quality of the T cell response plays a pivotal role in vaccine development.
The constantly growing number of available markers demands a consensus in the definition of T cell populations. The memory panel was used to measure stages of T cell maturation. In the norm group distribution within the stages differed in CD4 and CD8 cells. It has yet to be defined which deviations have clinical significance.
In collaboration with the gene therapy working group from the Department of Biochemistry the T cell response to a tumor vaccine was characterized. In these experiments the cytokine panel showed significant differences in the effect achieved by the transfection of different cytokines into tumor cells to stimulate the allogeneic T cell response after 24h of incubation
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
Cardiac biomarkers in chronic kidney disease are independently associated with myocardial edema and diffuse fibrosis by cardiovascular magnetic resonance
No full textBackground: High sensitivity cardiac troponin T (hs-cTnT) and NT-pro-brain natriuretic peptide (NT-pro BNP) are often elevated in chronic kidney disease (CKD) and associated with both cardiovascular remodeling and outcome. Relationship between these biomarkers and quantitative imaging measures of myocardial fibrosis and edema by T1 and T2 mapping remains unknown. Methods: Consecutive patients with established CKD and estimated glomerular filtration rate (eGFR) < 59 ml/min/1.73 m2 (n = 276) were compared to age/sex matched patients with eGFR ≥ 60 ml/min/1.73 m2 (n = 242) and healthy controls (n = 38). Comprehensive cardiovascular magnetic resonance (CMR) with native T1 and T2 mapping, myocardial ischemia and scar imaging was performed with venous sampling immediately prior to CMR. Results: Patients with CKD showed significant cardiac remodeling in comparison with both healthy individuals and non-CKD patients, including a stepwise increase of native T1 and T2 (p < 0.001 between all CKD stages). Native T1 and T2 were the sole imaging markers independently associated with worsening CKD in patients [B = 0.125 (95% CI 0.022–0.235) and B = 0.272 (95% CI 0.164–0.374) with p = 0.019 and < 0.001 respectively]. At univariable analysis, both hs-cTnT and NT-pro BNP significantly correlated with native T1 and T2 in groups with eGFR 30–59 ml/min/1.73 m2 and eGFR < 29 ml/min/1.73 m2 groups, with associations being stronger at lower eGFR (NT-pro BNP (log transformed, lg10): native T1 r = 0.43 and r = 0.57, native T2 r = 0.39 and r = 0.48 respectively; log-transformed hs-cTnT(lg10): native T1 r = 0.23 and r = 0.43, native T2 r = 0.38 and r = 0.58 respectively, p < 0.001 for all, p < 0.05 for interaction). On multivariable analyses, we found independent associations of native T1 with NT-pro BNP [(B = 0.308 (95% CI 0.129–0.407), p < 0.001 and B = 0.334 (95% CI 0.154–0.660), p = 0.002 for eGFR 30–59 ml/min/1.73 m2 and eGFR < 29 ml/min/1.73 m2, respectively] and of T2 with hs-cTnT [B = 0.417 (95% CI 0.219–0.650), p < 0.001 for eGFR < 29 ml/min/1.73 m2]. Conclusions: We demonstrate independent associations between cardiac biomarkers with imaging markers of interstitial expansion, which are CKD-group specific. Our findings indicate the role of diffuse non-ischemic tissue processes, including excess of myocardial fluid in addition to diffuse fibrosis in CKD-related adverse remodeling
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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