974 research outputs found
Dessin et rationalisation chez l'enfant (II)
No full textDenner Annette. Dessin et rationalisation chez l'enfant (II). In: Enfance, tome 7, n°1, 1954. pp. 41-70
Measurement of triple gauge boson couplings from W⁺W⁻ production at LEP energies up to 189 GeV
No full textA measurement of triple gauge boson couplings is presented, based on W-pair data recorded by the OPAL detector at LEP during 1998 at a centre-of-mass energy of 189 GeV with an integrated luminosity of 183 pb⁻¹. After combining with our previous measurements at centre-of-mass energies of 161–183 GeV we obtain κ = 0.97_{-0.16}^{+0.20}, g_{1}^{z} = 0.991_{-0.057}^{+0.060} and λ = -0.110_{-0.055}^{+0.058}, where the errors include both statistical and systematic uncertainties and each coupling is determined by setting the other two couplings to their Standard Model values. These results are consistent with the Standard Model expectations
Central insulin dysregulation and energy dyshomeostasis in two mouse models of Alzheimer's disease
No full textAlzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide. While the causes of AD are not known, several risk factors have been identified. Among these, type two diabetes (T2D), a chronic metabolic disease, is one of the most prevalent risk factors for AD. Insulin resistance, which is associated with T2D, is defined as diminished or absent insulin signaling and is reflected by peripheral blood hyperglycemia and impaired glucose clearance. In this study, we used complementary approaches to probe for peripheral insulin resistance, central nervous system (CNS) insulin sensitivity and energy homeostasis in Tg2576 and 3xTg-AD mice, two widely used animal models of AD. We report that CNS insulin signaling abnormalities are evident months before peripheral insulin resistance. In addition, we find that brain energy metabolism is differentially altered in both mouse models, with 3xTg-AD mice showing more extensive changes. Collectively, our data suggest that early AD may reflect engagement of different signaling networks that influence CNS metabolism, which in turn may alter peripheral insulin signaling. (C) 2017 Elsevier Inc. All rights reserved
Nachtstukken /
No full text1. De zandman ; De jesuitenkerk te G... . --2. Ignatius Denner ; Het sanctusEuropeana-GoogleBook
Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome
No full textBackground: Detection of a retrovirus, xenotropic murine leukaemia virus-related virus (XMRV), has recently been reported in 67% of patients with chronic fatigue syndrome. We have studied a total of 170 samples from chronic fatigue syndrome patients from two UK cohorts and 395 controls for evidence of XMRV infection by looking either for the presence of viral nucleic acids using quantitative PCR (limit of detection <16 viral copies) or for the presence of serological responses using a virus neutralisation assay.
Results: We have not identified XMRV DNA in any samples by PCR (0/299). Some serum samples showed XMRV neutralising activity (26/565) but only one of these positive sera came from a CFS patient. Most of the positive sera were also able to neutralise MLV particles pseudotyped with envelope proteins from other viruses, including vesicular stomatitis virus, indicating significant cross-reactivity in serological responses. Four positive samples were specific for XMRV.
Conclusions: No association between XMRV infection and CFS was observed in the samples tested, either by PCR or serological methodologies. The non-specific neutralisation observed in multiple serum samples suggests that it is unlikely that these responses were elicited by XMRV and highlights the danger of over-estimating XMRV frequency based on serological assays. In spite of this, we believe that the detection of neutralising activity that did not inhibit VSV-G pseudotyped MLV in at least four human serum samples indicates that XMRV infection may occur in the general population, although with currently uncertain outcomes
Data for the paper "Dispersion of particles in a sessile droplet evaporating on a heated substrate"
No full text<p><span><span>This file contains the data generated for each case demonstrated in the paper titled "Dispersion of particles in a sessile droplet evaporating on a </span>heated substrate" <br>Authors: Aman Kumar Jain, Fabian Denner, and Berend van Wachem. <br><br>The repository contains the 7 folders for 7 cases performed in stage 2 of the simulation described in table 4 of the paper. Cases C1 and C2 involve a droplet on a substrate at Ts = 25 ◦ C, while C3 and C4 involve a substrate at Ts = 50 ◦C. Marangoni stresses are considered in the even-numbered cases and neglected in the odd-numbered ones. The case names ending with suffix S denotes the standard silica particles and the case names ending with suffix N denotes neutrally buoyant articles. <br></span></p>
<p><span>Along with these folders a python script "ParticleCombined.py" is added which uses the particle position data in each case folder to calculate the particle surface density. <br><br>Each case folder contains: <br>The fluid fields, mesh, and particle information are stored in folders Fields, DMs, Meshes and Particles. <br>A .xmf wrapper file is provided to read the simulation results in Paraview. <br>The "results.xmf" file shows the fluid data such as velocity, pressure and liquid volume fraction. The liquid volume fraction value, alpha, tracks the interface of an evaporating sessile droplet. <br>The "results_DEM.xmf" shows the particle data such as the position, velocity and other data sets associated with the particles. <br><br>Each case folder contains five *.csv files which contain the information of particle position for 5-time instances and are processed using the python script "ParticleCombined.py". <br><br>This research was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), grant number 452916560.<br></span></p>
The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes-- executive summary
No full textThe International Xenotransplantation Association islet xenotransplantation consensus statement describes the conditions for undertaking clinical trials of porcine islet products in type 1 diabetes. Chapter 1 reviews the key ethical requirements and progress toward the definition of an international regulatory framework for clinical trials of xenotransplantation. Chapters 2 to 7 provide in depth and agreed-upon recommendations on source pigs, pig islet product manufacturing and release testing, preclinical efficacy and complication data required to justify a clinical trial, strategies to prevent transmission of porcine endogenous retrovirus, patient selection for clinical trials, and informed consent. It is planned to update this initial consensus statement in a year's time in light of progress in research, changes in the regulatory framework, and comments submitted after publication
Cell cycle-dependent and induced phosphorylation of p21 in eukaryotic cells
No full text1\. Titelblatt und Inhaltsverzeichnis
2\. Einleitung
3\. Material und Methoden
4\. Ergebnisse
5\. Diskussion und Ausblick
6\. Zusammenfassung & Summary
7\. Literaturverzeichnis
8\. Anhang
9\. DanksagungIn dieser Arbeit wird erstmalig eine noch unbekannte zellzyklusabhängige
Phosphorylierung des zytostatischen CDK-Inhibitors p21 vorgestellt. p21 wird
hierbei zu Beginn der Mitose im Zellkern am Thr-145 phosphoryliert. Es
konzentriert sich im weiteren Verlauf der Mitose in spezifischen
Kompartimenten der sich teilenden Zelle. Nach anfänglicher, diffuser
Verteilung innerhalb des Zellkerns (Prophase) ist es im weiteren Prozess der
Mitose ausschließlich an den Spindelpolen (Prometa- und Metaphase), später
jedoch nur noch an der Teilungsfurche (Telophase) und im Bereich des
kontraktilen Ringes (Zytokinese) zu detektieren. In eukaryotischen Zellen
während der Interphase ist p21 nicht phosphoryliert. Die spezifische,
zeitabhängige Lokalisation an den Spindelpolen und später im Bereich des
kontraktilen Rings lassen auf verschiedene Funktionen schließen, die
p-p21-Thr145 im Prozess der Mitose erfüllt. Bisherige Arbeiten beschreiben die
induzierte Phosphorylierung von p21 am Thr-145 nach Substanzbehandlung oder
Proteintransfektion in der G1-, S- und G2-Phase des Zellzyklus. Hierbei konnte
eine proliferative und anti-apoptotische Wirkung nachgewiesen werden. Aufgrund
der vorliegenden Daten muss also zwischen der zellzyklusabhängigen
Phosphorylierung von p21 in der Mitose und der induzierten Phosphorylierung
während der Interphase unterschieden werden. Die induzierte Phosphorylierung
kann durch Fehlregulationen von Kinasen verursacht werden, deren
Überexpression in verschiedenen Tumorarten festgestellt wurde. Zu diesen
Kinasen gehört Pim-1. Um die Interaktion zwischen Pim-1 und p21 in lebenden
Zellen zu untersuchen, wurden beide mit autofluoreszierenden Proteinen
markiert. Zunächst wurden die p21- und Pim-1-spezifischen Funktionen der
Fusionsproteine in biochemischen und zellbasierten Experimenten überprüft. In
anschließenden Transfektionsstudien konnte die Phosphorylierung von endogenem
p21 durch Pim-1-WT-GFP im Zellkern eukaryotischer Zellen festgestellt werden.
Die Phosphorylierung von endogenem p21 durch Pim-1-WT-GFP führte zudem zu
einer Translokation von p-p21-Thr145 in das Zytosol. Hier kann es an den
Mitochondrien mit Procaspase-3 interagieren und so den Fas-vermittelten
Apoptoseweg inhibieren. Die induzierte, unkontrollierte Phosphorylierung des
zytostatischen Zellzyklusinhibitors p21 durch erhöhte Pim-1-Enzymaktivität,
kann so eine proliferative und anti-apoptotische Wirkung auf die Zelle haben
und deren unkontrolliertes Wachstum fördern. Zusätzlich wird in der
vorliegenden Studie ein neu entwickelter funktioneller HCA-Assay vorgestellt,
mit dem anhand der Thr-145-Phosphorylierung von endogenem p21 durch Pim-1-WT-
GFP potentielle Pim-1-Inhibitoren in lebenden Zellen analysiert werden können.
Die Phosphorylierung von p21 wurde hierbei als Maß der Pim-1-WT-GFP-
Enzymaktivität und reziprok für die Wirksamkeit eines potentiellen Inhibitors
unter zellulären Bedingungen verwendet.The protein p21 is involved in several regulating processes during the G1, S
and G2 phase of the cell cycle. In the present study, we demonstrated that p21
is also involved in the process of mitosis. At the onset of mitosis, p21 is
phosphorylated at Thr-145 and accumulates at the spindle poles where it
remains until chromosomes segregation occurs. At the beginning of cytokinesis,
phosphorylated p21 shuttles from the centrosomes to the cleavage furrow and
seems to be associated with the contractile ring until the end of mitosis. The
localization of p-p21-Thr145 within specific compartments during mitosis
transition implies its participation in functional processes where at first
the centrosomes and later the contractile ring are involved in. Previous
publications described an induced phosphorylation of p21 at Thr145 after cell
treatment during the interphase of the cell cycle. This phosphorylation
inhibited the cytostatic properties of p21 in these cells and caused
proliferative and anti-apoptotic effects. For that reason, it is important to
distinguish between the cell cycle dependent phosphorylation of p21 during
mitosis progression and the induced phosphorylation during the interphase of
the cell cycle. The induced phosphorylation can be a result of dysregulated
kinases which are upregulated in several types of cancer. Pim-1 is one of
these tumor related kinases. Pim-1 and p21 were attached to autofluorescent
proteins to study their interactions in living cells. The proper functions of
the fusion proteins were proved in biochemical and cell based assays. This
study demonstrates that increased expression of Pim-1-WT-GFP leads to the
phosphorylation of endogenous p21 within the nucleus. Additionally,
p-p21-Thr145 was also detected within the cytosol in a subpopulation of these
cells. Here it can interact with procaspase-3 or ASK1, preventing the
induction of apoptosis. The induced phosphorylation as a result of increased
Pim-1 enzyme activity can lead to proliferative and anti apoptotic effects,
both of which can actively contribute to tumorigenesis. Furthermore, the Pim-1
-WT-GFP dependent phosphorylation of endogenous p21 was used to analyse the
effect of potential Pim-1 inhibitors under cellular conditions in a new
functional HCA assay. The intracellular phosphorylation of p21 was used as a
read out parameter for the Pim-1 enzyme activity and for the effect of the
potential Pim-1 inhibitors, respectively
Motion: a novel of young adult fiction and an accompanying exegesis
No full textThis practice-led PhD is comprised of a Young Adult Fiction novel entitled Motion, and an accompanying exegesis that reflects upon the ways in which an author employs creative expression and techniques during the creative journey, and the resulting impact of these choices upon the text. A discussion of YAF as a genre is entered into, and a how the novel's exploration of stereotyping, girls and sport, poverty, and violence sit within the context of fiction and adolescent culture
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