Elongation, proliferation & migration differentiate endothelial cell phenotypes and determine capillary sprouting

<p>Abstract</p> <p>Background</p> <p>Angiogenesis, the growth of capillaries from preexisting blood vessels, has been extensively studied experimentally over the past thirty years. Molecular insights from these studies have lead to therapies for cancer, macular degeneration and ischemia. In parallel, mathematical models of angiogenesis have helped characterize a broader view of capillary network formation and have suggested new directions for experimental pursuit. We developed a computational model that bridges the gap between these two perspectives, and addresses a remaining question in angiogenic sprouting: how do the processes of endothelial cell elongation, migration and proliferation contribute to vessel formation?</p> <p>Results</p> <p>We present a multiscale systems model that closely simulates the mechanisms underlying sprouting at the onset of angiogenesis. Designed by agent-based programming, the model uses logical rules to guide the behavior of individual endothelial cells and segments of cells. The activation, proliferation, and movement of these cells lead to capillary growth in three dimensions. By this means, a novel capillary network emerges out of combinatorially complex interactions of single cells. Rules and parameter ranges are based on literature data on endothelial cell behavior in vitro. The model is designed generally, and will subsequently be applied to represent species-specific, tissue-specific in vitro and in vivo conditions.</p> <p>Initial results predict tip cell activation, stalk cell development and sprout formation as a function of local vascular endothelial growth factor concentrations and the Delta-like 4 Notch ligand, as it might occur in a three-dimensional in vitro setting. Results demonstrate the differential effects of ligand concentrations, cell movement and proliferation on sprouting and directional persistence.</p> <p>Conclusion</p> <p>This systems biology model offers a paradigm closely related to biological phenomena and highlights previously unexplored interactions of cell elongation, migration and proliferation as a function of ligand concentration, giving insight into key cellular mechanisms driving angiogenesis.</p

Charting Disaster Recovery via Google Street View: A Social Science Perspective on Challenges Raised by the Fukushima Nuclear Disaster

There is increasing interest in using Google Street View (GSV) for research purposes, particularly with regard to “virtually auditing” the built environment to assess environmental quality. Research in this field to date generally suggests GSV is a reliable means of understanding the “real world” environment. But limitations around the dates and resolution of images have been identified. An emerging strand within this literature is also concerned with the potential of GSV to understand recovery post-disaster. Using the GSV data set for the evacuated area around the Fukushima Dai’ichi nuclear power plant as a case study, this article evaluates GSV as a means of assessing disaster recovery in a dynamic situation with remaining uncertainty and a significant value and emotive dimension. The article suggests that GSV does have value in giving a high-level overview of the post-disaster situation and has potential to track recovery and resettlement over time. Drawing on social science literature relating to Fukushima, and disasters more widely, the article also argues it is imperative for researchers using GSV to reflect carefully on the wider socio-cultural contexts that are often not represented in the photo montage

Evaluation of quantified contrast-enhanced color and power Doppler ultrasonography for the assessment of vascularity and perfusion of naturally occurring tumors in dogs

OBJECTIVE: To investigate subjective and computerized methods of evaluation of color Doppler (CD) and power Doppler (PD) ultrasonographic images (obtained before and after administration of contrast medium) for quantitative assessment of vascularity and perfusion of various naturally occurring tumors in dogs. SAMPLE POPULATION: 34 tumors in 34 dogs. PROCEDURE: Tumors in dogs were examined via CD and PD ultrasonography before and after i.v. injection of a microbubble contrast agent (pre- and postcontrast examinations, respectively). Images were digitized for subjective assessment of vessel density and vascular pattern and computer-aided assessment of parameters of vascularity (fractional area [FA]) and perfusion (color-weighted FA [CWFA] and mean color-weighted FA [CWFA] and mean color level). RESULTS: With both analysis methods, more vessels were identified in precontrast PD ultrasonographic images than in precontrast CD ultrasonographic images. Moreover, compared with values for precontrast PD ultrasonography, FA, CWFA, and mean color level were higher for postcontrast PD ultrasonography. In postcontrast images, there was a significant association between vessel densities determined through subjective and computerized assessments. Although sample size was small, vascularity of squamous cell carcinomas was significantly greater than that of other tumor types. Ten of the 19 softer than issue that sarcomas had low vessel density with minor contrast enhancement. With increasing gross tumor volume, FA and CWFA decreased for all Doppler ultrasonographic methods. CONCLUSIONS AND CLINICAL RELEVANCE: Higher values of the ultrasonographic parameters representing vascularity and perfusion of tumors in dogs were determined via PD ultrasonography after administration of contrast medium than via PD or CD ultrasonography without administration of contrast medium