140 research outputs found

    Hanen og raeven fra The Canterbury Tales

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    Here is the Danish version of Chanticleer and the Fox published by Thomas Y. Crowell in 1958. This version features the same cover picture showing the main characters, including both the rooster and the fox. It even uses the same design for its endpapers. As I wrote there, this is an enjoyable large-format book for children. The whole argument about dreams is dropped from the original. The best illustrations are those introducing Chanticleer and the fox (about 12 and 20, respectively). How nice to meet an old friend in a new place! A web reference seems to confirm that it was published in 1958.This is a hardbound book (hard cover)Language note: Danishaf Geoffrey Chaucer. Oversat af Cecil Bødke

    Figure 4. Pulmonary gene expression profiles of genes related to T-cells, B-cells, MHC-I and II and novel genes in protected and unprotected mice following B. pertussis challenge.

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    Expression profiles of genes in the lungs related to (A) T-cells, (B) B-cells, (C) and antigen presentation by MHC-I and MHC-II were selected according to GO-BP terms, KEGG pathways and text mining. In addition, genes with unknown or poorly understood function that showed interesting gene expression profiles in protected mice were listed as (D) novel genes. Additionally, the color codes of the six clusters from Figure 2 are added

    Figure 5. Cytokine profiles in the lungs following B. pertussis challenge in unprotected and protected mice.

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    Pulmonary concentrations of (A) CCL4, (B) CCL11, (C) VEGF, (D) G-CSF, (E) CXCL1, (F) CXCL2, (G) CXCL5, (H) CXCL9, (I) CXCL10, (J) IL-17A, (K) IL-5, (L) TNFα and (M) M-CSF were analyzed before and after a B. pertussis challenge in unprotected (lighter blue bars) and protected (dark blue and red bars) mice, as indicated. Data represented as mean concentrations of individual values (n = 3). Significant values were calculated by one-way ANOVA with multiple comparison compared to the pre-challenge level (D0) of unprotected mice or protected mice (* = pp<0.01, and *** = pp<0.0001)

    Figure 7. Serum and pulmonary antibody profiles in unprotected and protected mice following B. pertussis challenge.

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    Serum IgA, IgG, and IgG subclass responses specific for (A) OMV, (B) Ptx, (C) Prn, (D) FHA, and (E) Fim2/3 were determined by using a MIA. Data were obtained in naive mice and protected mice prior to challenge (D0) and 14 days post infection (p.i.) or 14 days post-challenge (p.c.) (n=3/time point). (F) Pulmonary IgA responses against these antigens were determined on the same time points. * = p<0.05 experimental group versus unprotected group (D0), + = p<0.05 protected group (D0) versus protected group (14 days p.c.). (G) The kinetics of the anti-OMV IgA antibody formation in lung lysates were analyzed at more time points (n=3/time point) and expressed in fluorescence intensity (F.I.). **** = p<0.0001, challenged unprotected or protected group versus unprotected or protected group (day 0), ++ and +++ = p<0.01 and p<0.001 unprotected group versus protected group (for each time point). (H) Western blot on separated B. pertussis B1917 proteins was performed with pooled lung lysates (1:50) of unprotected and protected mice prior to challenge (D0), and of protected mice 14 days p.c. with IR800-labeled secondary antibody. Left panel shows whole protein range (260kDa-B. pertussis lysate. Right panel shows more detailed separation of the 110-60kDa protein range. Antigen identification for Vag8 and LPS is depicted

    Figure 6. Serum cytokine profiles and percentage of splenic neutrophils following B. pertussis challenge in unprotected and protected mice.

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    (A) The serum concentrations of 33 cytokines were analyzed before and after a B. pertussis challenge in unprotected (lighter blue bars) and protected (dark blue and red bars) mice, as indicated. Concentrations of CXCL13, CCL11, CXCL1, G-CSF, IL-6, CXCL10, and IL-13 serum were significantly altered and represented as mean concentrations of individual values (n = 3). Significant values were calculated by one-way ANOVA with multiple comparison compared to the pre-challenge level (D0) of unprotected mice or protected mice (* = ppp<0.001). (B) The percentage of Gr1+ cells (neutrophils) was determined over time in the spleen of unprotected and protected mice by using Flow cytometry (* = p <br

    Systems vaccinology : molecular signatures of immunity to Bordetella pertussis

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    The worldwide resurgence of whooping cough (pertussis), even in highly vaccinated populations, demands improved pertussis vaccines. In this thesis a systems vaccinology approach is applied to deepen knowledge of the immune responses evoked by different pertussis vaccines and compare this with a Bordetella pertussis infection since the latter induces robust protection. Infection-induced responses in mice conferred sterilizing protection that is caused by systemic immunity but more importantly by mucosal IgA, T-helper (Th)1/Th17 responses, and ‘trained’ innate immune cells in the lungs. An experimental outer membrane vesicle vaccine (omvPV) was compared with the two licensed vaccines, acellular vaccine (aPV), whole-cell vaccine (wPV) as well as a B. pertussis infection. OmvPV evoked a different immunoproteomic profile with respect to antibody levels, antigen specificity, and subclass distribution. Furthermore, omvPV confers equal protection in mice as wPV, but with a lower inflammatory response. In this thesis it is also shown that the immunization route is critical. Although subcutaneous omvPV immunization is effective, pulmonary administration lead to superior protection, comparable to infection-induced immunity and included hallmarks of protection such as pulmonary Th17 cells and mucosal IgA. The molecular and cellular signatures described in this thesis may have an important contribution to enhanced pertussis immunity

    Figure 1. Design and baseline parameters of a B. pertussis challenge model in protected and naive unprotected mice.

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    (A) Schematic diagram of animal pre-treatment, sacrifice, sampling and systems analysis on 4 hours and 2, 7, 10 and 14 days p.c. in a B. pertussis challenge model in protected and unprotected BALB/c mice. Pulmonary transcriptomic profile, percentage of splenic Gr1+ cells (neutrophils), serum and lung cytokine profiles, serum and lung antibody profiles, and specific splenic CD4+CD44+ T-cells were assessed at the given time points in protected and unprotected mice. (B)  Study parameters at baseline (D0) of naive unprotected mice and protected mice, 56 days after primary infection, including time frames of lung clearance, systemic T-helper subsets, serum IgG profile, mucosal IgA, and pulmonary transcriptomic profile as obtained from data in the current study and data adapted from our previous study (10). 320 genes are differential expressed in protected mice compared to naive (D0 unprotected) mice. (C) An overrepresentation analysis was performed using DAVID for Keywords, KEGG-pathways, and gene ontology biological pathways (GO-BP) to determine the function of the 320 genes. For each term, the number of upregulated (red) and downregulated (green) genes are depicted

    Figure 3. Pulmonary gene expression profiles of membrane proteins and secreted proteins in protected and unprotected mice following B. pertussis challenge.

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    Expression profiles of genes in the lungs encoding membrane proteins (left panel) and secreted proteins (right panel) were selected according to GO-BP terms, KEGG pathways and text mining. Each list is divided in four groups (A-D) based on their expression profile on 4 hours and 2 days p.c. Group A contains genes that are significantly upregulated in unprotected mice, but unaltered in protected mice. Group B covers genes that are not upregulated on 4 hours and 2 days p.i. in unprotected mice, but are directly activated in protected mice. Group C comprehends genes that are upregulated on 4 hours and/or 2 days p.c. in both protected and unprotected mice. Group D includes genes that are significantly regulated from 7 days p.c. in both protected and unprotected mice. In addition, the color codes of the six clusters from Figure 2 are added

    Figure 2. Pulmonary gene expression profiles in protected and unprotected mice following a B. pertussis challenge.

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    (A) Fold changes in gene expression of both unprotected and protected mice were calculated compared to naive mice (D0 unprotected). The expression results (FR≥1.5, p-value≤0.001) are visualized as heatmap (mean of n = 3). Genes not exceeding a fold change of 1.5 are depicted as basal level (black) at this time point. In total, 786 genes were found to be differentially regulated. Genes were divided in six clusters (I-VI) based on their expression profiles (color coding for these clusters is depicted in an additional table): cluster I (Differential expression in unprotected mice, absent in protected mice), Cluster II (Differential expression in unprotected mice and protected mice), Cluster III (Differential expression in unprotected mice and in protected mice before and after challenge), Cluster IV (Differential expression in unprotected mice and additional differential expression as result of challenge in protected mice), Cluster V (Absent in unprotected mice but differential expression in protected mice) and Cluster VI (absent in unprotected mice but differential expression pre- and post-challenge in protected mice). (B) Transcriptomic profiles obtained on 2 days p.i. in unprotected and 2 days p.c. protected mice were compared by plotting all 786 genes in a scatter plot and divide the genes in different fractions based on co-expression. The black solid lines are the thresholds for the significant FR (FR ≥ 1.5 or ≤ 0.67) compared to naive mice (D0 unprotected) for both unprotected and protected mice. Black dots represent genes that are not significantly regulated compared to naive mice (D0 unprotected) in both groups. The red solid lines represent the threshold for the significant FR (FR ≥ 1.5 or ≤ 0.67) of both unprotected 2 days p.i. and protected mice 2 days p.c. All red triangles represent genes that show significant differential expression (FR ≥ 1.5 or ≤ 0.67) between unprotected  2 days p.i. and protected mice 2 days p.c. In total, 212 genes were differentially expressed between both groups of which 108 genes were upregulated and 104 were downregulated. These genes were divided in eight fractions that are significantly up-regulated (1-4) or downregulated (5-8) in protected mice compared to unprotected mice and are further specified as heatmaps in Supplementary Figure 1B. Dots with other colors (orange, green, brown, and blue) represent genes that are significantly regulated in unprotected and/or protected mice compared to naive mice (D0 unprotected) but these genes are not differentially regulated between unprotected 2 days p.i. and protected mice 2 days p.c. (C-D) A selection of eight terms (KEGG-pathways and GO-BP terms) found enriched in the ORA of the 786 genes and the kinetics over time of indicated terms is depicted. (C) Kinetics was determined by averaging the FR for each term at each time point and is expressed on LN-scale. (D) For each enriched term, the Benjamini score and the number of upregulated (red) and downregulated (green) genes in the protected mice and unprotected mice is shown

    Measurements of the mass and width of W boson from e&quot;+e&quot;- -&gt; W&quot;+W&quot;- -. (e/#mu#)#nu#qq&quot;- events with the ALEPH detector

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    In 1998 at CERN (Geneva), 174 pb&quot;-&quot;1 of data was collected with the ALEPH detector, at an e&quot;+e&quot;- centre-of-mass energy of 188.6 GeV. For this dataset, the selection of semi-leptonic decays of W boson pairs (WW #-&gt;# (e/#mu#)#nu#qq-bar) is improved. The resulting efficiencies for selecting e#nu#qq-bar and #mu##nu#qq-bar events are 82.0% and 88.1% respectively, with purities of 92.4% and 93.3%. For the first time in ALEPH, the width of the W boson is measured using a two parameter (mass M_W and width #GAMMA#_W) fit to the reconstructed W mass distribution, yielding: M_W = 80.313 #+-#0.119(stat.) #+-# 0.052(syst.) GeV/c&quot;2; #GAMMA#_W 2.17_-_0_._2_6_&quot;+&quot;0&quot;.&quot;2&quot;9&quot;(stat.) #+-# 0.11(syst.) GeV/c&quot;2, for e#nu#qq-bar and #mu##nu#qq-bar decays combined. The mass value is in good agreement with the world average mass and the width value is in good agreement with Standard Model calculations. The systematic error includes detector uncertainties as well as uncertainties in the background, the beam energy, and the theoretical model. Additional studies are done with respect to previous years to take into account errors in the angular and energy resolutions of the ALEPH detector. The stability of the data fit results is checked as a function of various selection cuts. A preliminary measurement is performed at centre-of-mass energies ranging from 191.6 to 201.6 GeV. These results are combined with the result above to obtain the preliminary result for a total integrated luminosity of 411 pb&quot;-&quot;1: M_W = 80.537 #+-# 0.079 #+-# 0.052 GeV/c&quot;2; #GAMMA#_W = 2.11_-_0_._1_8&quot;+&quot;0&quot;.&quot;2&quot;0 #+-# 0.11 GeV/c&quot;2. (author)Available from British Library Document Supply Centre-DSC:DXN038352 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo
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