2,768 research outputs found
Dalitz plot analyses of B-0 -> (D-DK+)-K-0 and B+-> (D)over-bar(-)D(0)K(+) decays
No full text© 2015, APS Journal
Dynamic x-ray imaging at the Munich Compact Light Source
No full textProceedings of the 14th International Conference on X-ray Microscopy (XRM2018)Regine Gradl ... Martiin Donnelley ... David Parsons ... et al
Identification of two regulatory elements within the high mobility group box transcription factor XTCF-4
No full textSome members of the Wnt family of extracellular glycoproteins regulate target gene expression by inducing stabilization and nuclear accumulation of beta -catenin, which functions as a transcriptional activator after binding to transcription factors of the T-cell factor! lymphoid enhancer factor (TCF/LEF) family. Three different members of this family have been identified in Xenopus laevis thus far that differ in their ability to influence mesodermal differentiation and to activate expression of the Wnt target gene fibronectin, Here we report on the isolation and characterization of additional variants of XTCF-4. We:show that the differential ability of these proteins and other members of the TCF family to activate target genes is neither due to preferential interaction with transcriptional cofactors of the groucho family or SMAD4 nor to different DNA binding affinities, Expression of these proteins in an epithelial cell line reveals differences in their ability to form a ternary complex with DNA and beta -catenin. Interestingly, formation of this ternary complex was not sufficient to activate target gene expression as previously thought. Our experiments identify two amino acid sequence motifs, LVPQ and SFLSS, in the central domain of XTCF-4 that regulate the formation of the DNA-TCF-beta -catenin complex or activation of target genes, respectively Biochemical studies reveal that the phosphorylation state of these XTCF-4 variants correlates with their ability to form a ternary complex with beta -catenin and DNA but not to activate target gene expression, The described variants of XTFC-4 with their different properties in complex formation provide strong evidence that in addition to the regulation of beta -catenin stability the isoforms of TCF/LEF transcription factors and their posttranslational modifications define the cellular response of a Wnt/wingless signal
Assessment of the peripheral microcirculation using computer-assisted venous congestion plethysmography in post-traumatic complex regional pain syndrome type I
No full textIn complex regional pain syndrome type I (CRPS-I), edema of the affected limb is a common finding. Therefore, the changes in macro- and microcirculatory parameters were investigated to elucidate the underlying pathophysiology. Twenty-four patients with post-traumatic CRPS-I and 25 gender- and age-matched healthy subjects were examined by means of an advanced computer-assisted venous congestion strain-gauge plethysmograph. The recording of the volume response of the forearm to a stepwise inflation of an occlusion cuff placed at the upper arm enabled the calculation of the arterial blood flow into the arm (Q(a)), the vascular compliance (C), the peripheral venous pressure (P-v), the isovolumetric venous pressure (P-vi; = hydrostatic pressure needed to achieve net fluid filtration) and the capillary filtration capacity (CFC) - an index of microvascular permeability. The study revealed no difference in any of the parameters between the right and left hand of healthy subjects. In CRPS-I patients, however Qs, Pv, Pvi and CFC were significantly (p < 0.01/0.001) elevated in the affected arm (Q(a) 11.2 +/- 7.0 ml min(-1) 100 ml(-1), P-v 20.2 +/- 8.1 mm Hg, P-vi 24.7 +/- 4.2 mm Hg, CFC 0.0058 +/- 0.0015 ml min(-1) 100 ml(-1) mm Hg-1) compared to the unaffected arm (Q(a) 4.2 +/- 2.4 ml min(-1) 100 ml(-1), P-v 10.0 +/- 5.1 mm Hg, P-vi 13.2 +/- 3.7 mm Hg, CFC 0.0038 +/- 0.0005 ml min(-1) 100 ml(-1) mm Hg-1) and the values obtained in healthy controls (Q(a) 5.1 +/- 1.3 ml min(-1) 100 ml(-1), P-v 10.4 +/- 4.3 mm Hg, P-vi 15.7 +/- 3.3 mm Hg, CFC 0.0048 +/- 0.0012 ml min(-1) 100 ml(-1) mm Hg-1). Whereas the values in the unaffected arm of CRPS-I patients revealed no difference in Q(a), P-v and P-vi but a lower CFC (p < 0.01) compared to those from healthy controls. These results suggest profound changes in both macro- and microvascular perfusion in the affected arm of CRPS-I patients. The high CFC contributes to the edema formation, and combined with the elevated Pvi, they are in agreement with the hypothesis of an inflammatory origin of CRPS. Copyright (C) 2001 S. Karger AG, Basel
Dalitz plot analyses of B-0 -> (D-DK+)-K-0 and B+-> (D)over-bar(-)D(0)K(+) decays
No full textWe present Dalitz plot analyses for the decays of B mesons to (D-DK+)-K-0 and (D) over bar (DK+)-D-0-K-0. We report the observation of the D*(s1)(2700)(+) resonance in these two channels and obtain measurements of the mass M(D*(s1)(2700)(+)) = 2699(-7)(+14) MeV/c(2) and of the width Gamma(D*(s1)(2700)(+)) = 127(-19)(+24) MeV, including statistical and systematic uncertainties. In addition, we observe an enhancement in the (DK+)-K-0 invariant mass around 2350-2500 MeV/c(2) in both decays B-0 -> (D-DK+)-K-0 and B+ -> (D) over bar (DK+)-D-0-K-0, which we are not able to interpret. The results are based on 429 fb(-1) of data containing 471 x 10(6) B (B) over bar pairs collected at the Upsilon(4S) resonance with the BABAR detector at the SLAC National Accelerator Laboratory
Wnt 5a signaling is critical for macrophage-induced invasion of breast cancer cell lines
No full textInteractions between neoplastic and stromal cells contribute to tumor progression. Wnt genes, involved in cell migration and often deregulated in cancers, are attractive candidates to regulate these effects. We have recently shown that coculture of breast cancer cells with macrophages enhances invasiveness via matrix metal loproteases and TNF-alpha. Here we demonstrate that coculture of MCF-7 cells and macrophages leads to up-regulation of Writ 5a in the latter. This was accompanied by activation of AP-1/c-Jun in MCF-7. Recombinant Writ 5a mimicked the coculture effect. Writ 5a was also detectable in tumor-associated macrophages in primary breast cancers. Experiments with agonists and antagonists of Writ signaling revealed that a functional canonical pathway in the tumor cells was a necessary prerequisite; however, noncanonical signaling via Writ 5a and the Jun-N-terminal kinase pathway was critical for invasiveness. It was also responsible for induction of matrix metalloprotease-7, known to release TNF-alpha. All these effects could be antagonized by dickkopf-1. Our results indicate that Wnt 5a is essential for macrophage-induced invasiveness, because it regulates tumor cell migration as well as proteolytic activity of the macrophages. The function of Writ 5a as either a suppressor or promoter of malignant progression seems to be modulated by intercellular interactions. Writ 5a detection in tumor-associated macrophages in breast cancer biopsies supports the assumption that similar events play a role in vivo.Medical Research Council [G0601867
In vivo x-ray imaging of the respiratory system using synchrotron sources and a compact light source.
No full textBright synchrotron x-ray sources enable imaging with short exposure times, and hence in a high-speed image sequence. These x-ray movies can capture not only sample structure, but also how the sample changes with time, how it functions. The use of a synchrotron x-ray source also provides high spatial coherence, which facilitates the capture of not only a conventional attenuation-based x-ray image, but also phase-contrast and dark-field signals. These signals are strongest from air/tissue interfaces, which means that they are particularly useful for examining the respiratory system. We have performed a range of x-ray imaging studies that look at lung function, airway surface function, inhaled and instilled treatment delivery, and treatment effect in live small animal models [Morgan, 2019]. These have utilized a range of optical set-ups and phase-contrast imaging methods in order to be sensitive to the relevant sample features, and be compatible with high-speed imaging. For example, we have used a grating interferometer to measure how the airsacs in the lung inflate during inhalation, via changes in the dark-field signal [Gradl, 2018], a single-exposure, single-grid set-up to capture changes in the liquid lining of the airways [Morgan, 2015] and propagation-based phase contrast to image clearance of inhaled debris [Donnelley, 2019]. Studies have also utilized a range of analysis methods to extract how the sample features change within a time-sequence of two-dimensional projections or three-dimensional volumes. While these imaging studies began in large-scale synchrotron facilities, we have recently performed these kinds of studies at an inverse-Compton-based compact synchrotron, the Munich Compact Light Source (MuCLS) [Gradl, 2018b]. 1. Morgan, Kaye, et al., "Methods for dynamic synchrotron X-ray imaging of live animals.", under review 01/2019. 2. Gradl, R., et al. "Dynamic in vivo chest x-ray dark-field imaging in mice." IEEE Transactions on Medical Imaging (2018). 3. Morgan, Kaye S., et al. "In vivo X-ray imaging reveals improved airway surface hydration after a therapy designed for cystic fibrosis." American Journal of Respiratory and Critical Care Medicine 190.4 (2014): 469-472. 4. Donnelley, Martin, et al. "Live-pig-airway surface imaging and whole-pig CT at the Australian Synchrotron Imaging and Medical Beamline." Journal of Synchrotron Radiation 26.1 (2019). 5. Gradl, Regine, et al. "In vivo Dynamic Phase-Contrast X-ray Imaging using a Compact Light Source." Scientific Reports 8.1 (2018b): 6788
CLARIAH-DE Cross-Service Search
No full textCLARIAH-DE combines services and offerings of CLARIN-D and DARIAH-DE. This includes various search applications which are made directly available to researchers. These search applications are presented in this working paper based on their main characteristics and compared with a focus on possible harmonizations. Opportunities and risks of different forms of technical integration are highlighted. Identified challenges can be explained in particular considering the background of different organizational and technical frameworks as well as highly specific and discipline-dependent requirements. The integration work that has already been carried out and the experiences gained with regard to future work and possible integration of further applications are also discussed. The experiences made in CLARIAH-DE can especially be of interest for other projects in the field of digital research infrastructures
Prospects and Benefits of Merging Subject-specific Services
No full textCLARIAH-DE combines services and offerings of CLARIN-D and DARIAH-DE. This includes various search applications which are made directly available to researchers. These search applications are presented in this working paper based on their main characteristics and compared with a focus on possible harmonizations. Opportunities and risks of different forms of technical integration are highlighted. Identified challenges can be explained in particular considering the background of different organizational and technical frameworks as well as highly specific and discipline-dependent requirements. The integration work that has already been carried out and the experiences gained with regard to future work and possible integration of further applications are also discussed. The experiences made in CLARIAH-DE can especially be of interest for other projects in the field of digital research infrastructures
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