How should novelty be valued in science?

<p>Box plot analysis of serum concentrations of sRAGE (A), esRAGE (B), S100A9 (C) and HMGB1 (D) in patients with CTEPH (n = 26) and controls (n = 33). Independent Student’s t-test was used to compare groups. <i>RAGE</i> receptor for advanced glycation endproducts, <i>sRAGE</i> soluble RAGE, <i>esRAGE</i> endogenous secretory RAGE, <i>S100A9</i> member of S100 family of Ca+ binding proteins, <i>HMGB1</i> high mobility group box1, <i>CTEPH</i> chronic thromboembolic pulmonary hypertension.</p

SEC^PBMC induces formation of new blood vessels.

<p>(<b>A</b>) Representative CD31 stainings of wounds underneath the original wound edge are shown. Scale bars: 50 µm (<b>B</b>) The numbers of CD31 positive cells underneath the newly formed epidermis were evaluated. The graph represents the mean of 15 animals in each group (*: p<0.01). (<b>C</b>) The area of the granulation tissue taken up by CD31⁺ cells was evaluated. The graph represents the mean of 15 animals in each group. (<b>D</b>) Cell cycle analysis of SEC^PBMC treated microvascular EC shows a strong increase in proliferating cells. VEGF treatment served as positive control. One representative experiment of three each done in triplicates is shown (*: p<0.01). (<b>E</b>) A tube formation assay is shown. Compared to medium alone SEC^PBMC strongly induced tube formation in a matrigel assay. One representative experiment of three is shown.</p

List of Antibodies.

<p>Company addresses:</p>1<p>Bedford, MA, USA; ²Littleton, CO, USA; ³Cambridge, UK; ⁴NEB: New England Biolabs, Beverly, MA, USA; ⁵Turku Finland; ⁶Buckinghamshire, UK; ⁷Rockford, IL, USA; ⁸Eugene, OR, USA. n.d.: not done.</p

SEC^PBMC induces migration of human primary fibroblasts and keratinocytes.

<p>Scratch wounds of FB (<b>A</b>) and KC (<b>D</b>) are shown. One representative experiment of three each done in triplicates is shown. The mean-width of the gaps of nine scratch wounds after 18 h was measured and the percentage of closure for FB (<b>B</b>) and KC (<b>E</b>) was calculated. (*: p<0.01). Cells cycle analyses revealed no significant differences in FB (<b>C</b>) and in KC (<b>F</b>). One representative experiment of three each done in triplicates is shown. (<b>G</b>) Ki67 staining of medium and SEC^PBMC treated wounds showed no significant alterations in proliferating cells. Photographs were taken at the wound-edge of wounds 7 days after wounding. Ki67 staining is shown in red and nuclear staining is shown in blue. C  =  crust, E  =  newly formed epidermis, G  =  granulation tissue HF  =  hair follicle. One representative animal of 15 is shown. Scale bars: 50 µm. (<b>H</b>) The mean from 15 animals per group of Ki67 positive cells at the wound edge of one high power image was calculated.</p

SEC^PBMC leads to enhanced wound closure and re-epithelialization.

<p>(<b>A</b>) Wound areas were measured during the first 3 days after wounding. Treatment with SEC^PBMC significantly enhanced wound closure. Error bars represent one standard deviation calculated from 15 animals for each set of values (*: p<0.05). (<b>B</b>) Representative photographs from mouse wounds (n = 15 from each group) immediately after wounding and at day 7 after wounding are shown. (<b>C</b>) H&E staining of wounds treated with medium or SEC^PBMC 7 days after wounding is shown. While medium treated wounds still show a thick crust and little re-epithelialization, SEC^PBMC treated wounds are fully re-epithelialized. C  =  crust, E  =  newly formed epidermis, G  =  granulation tissue. Scale bars: 100 µm. One representative animal of 15 is shown.</p

Calculation of the overlapping ratio of the transmural plus the non-transmural infarction by cardiac magnetic resonance imaging (cMRI) and NOGA endocardial mapping.

<p>A. cMRI transmurality polar map. B. NOGA bipolar polar map. C and D. Overlap of the cMRI and NOGA polar maps. a: The size of the transmural and non-transmural infarction by cMRI; b: the size of transmural and non-transmural infarction by NOGA bipolar mapping; c: overlap of the NOGA bipolar infarct shape on a cMRI polar map; d: overlap of the cMRI infarct shape on a NOGA bipolar map. The overlapping ratio was calculated as follows: (c+d)/(a+b).</p

Apoptotic MNC-secretomes in experimental stroke

<p>Mixed Model Analysis (SAS output)</p> <p>The data were analyzed using linear mixed models for the neuroscore on treatment group and time-point with the factor animal included as a random effect. The MIXED procedure in SAS 9.3 was used to perform the calculations. The raw output contains information on the model specifications, the estimated error variance and random effects variance, the estimated regression coefficients, the covariance structure of the model coefficients and type III F-tests for the hypotheses of no effect of either fixed effect or their interactions. An interaction plot was drawn using the GLM procedure. This plot shows the individual observations and their sample mean values in each group and for each time-point. The group labels 0,1,2 and 3 in the raw output refer to the treatment group in setting 1, the control group in setting 1, the treatment group in setting 2 and the control group in setting 2, respectively.</p> <p>Original Western blots to Figure 5 </p> <p>Expression of proteins involved in cytoprotective pathways in human Astrocytes and Schwann Cells </p> <p>Astrocytes (page 1) or Schwann Cells (page 2) were stimulated with hMNCapo sec, control medium (served as control to treatment) or positive control (control to the measured protein). Original blots for all measured proteins are given in this raw data set (pages 1 and 2). For each blot, lanes (1), (2), and (3) correspond to the groups medium control [(1)=control to treatment], human apoptotic MNC-secretomes [(2)=treatment] and positive control [(3)=recombinant protein].<br>Bands in each blot are shown for phosphorylated CREB, total-CREB, phosphorylated Erk1/2, total-Erk 1/2, phosphorylated HSP27, total-HSP27, phosphorylated cJun, total-cJun, phosphorylated Akt, and total-Akt. The molecular weight (kDa) for each protein can be seen under each blot.<br>Ponceau staining was used as loading control for each group (1), (2), and (3) and suggest equal loading.</p> <p>Original Western blots to Figure 6 </p> <p>Expression of Phosphorylated CREB in Astrocytes and Neurons after stimulation with the active compound hMNCapo sec or control medium: </p> <p>Cultured human Astrocytes and Neurons were incubated with hMNCapo sec or control (cell culture-) medium at indicated concentrations. Original blots can be seen here.<br>Ponceau staining shows equal loading.</p> <p> </p

SEC^PBMC leads to activation of several signaling cascades.

<p>KC, FB and EC were treated for 1 h with medium or SEC^PBMC. Western blot analyses of several signaling factors are shown. One representative experiment of three is shown. The graphs in the right panel represent the mean band intensity of all three experiments. The increase in expression of the phosphorylated proteins was calculated in relation to the respective non-phosphorylated proteins (*: p<0.01).</p

RAGE expression in TETs.

<p>Expression of RAGE in thymoma WHO type A (A), AB (B), B1 (C), B2 (D), B3 (E) and TC - SCC (F) is shown. Scale bar: 40 μm. <i>RAGE</i> receptor for advanced glycation endproducts, <i>TETs</i> thymic epithelial tumors, <i>WHO</i> World Health Organization, TC thymic carcinoma, <i>SCC</i> squamous cell carcinoma.</p

Serum concentrations of sRAGE and HMGB1 in benign and malignant thymic disease.

<p>The levels of circulating sRAGE (a), and HMGB1 (b) in serum of patients with TETs compared to patients with thymic hyperplasia and healthy volunteers are shown. <i>RAGE</i> receptor for advanced glycation endproducts, <i>sRAGE</i> soluble RAGE, <i>HMGB1</i> high mobility group box1, <i>TET</i> thymic epithelial tumor.</p