How river rocks round: resolving the shape-size paradox

River-bed sediments display two universal downstream trends: fining, in which particle size decreases; and rounding, where pebble shapes evolve toward ellipsoids. Rounding is known to result from transport-induced abrasion; however many researchers argue that the contribution of abrasion to downstream fining is negligible. This presents a paradox: downstream shape change indicates substantial abrasion, while size change apparently rules it out. Here we use laboratory experiments and numerical modeling to show quantitatively that pebble abrasion is a curvature-driven flow problem. As a consequence, abrasion occurs in two well-separated phases: first, pebble edges rapidly round without any change in axis dimensions until the shape becomes entirely convex; and second, axis dimensions are then slowly reduced while the particle remains convex. Explicit study of pebble shape evolution helps resolve the shape-size paradox by reconciling discrepancies between laboratory and field studies, and enhances our ability to decipher the transport history of a river rock.Comment: 11 pages, 5 figure

The user support programme and the training infrastructure of the EGI Federated Cloud

The EGI Federated Cloud is a standards-based, open cloud system as well as its enabling technologies that federates institutional clouds to offer a scalable computing platform for data and/or compute driven applications and services. The EGI Federated Cloud is based on open standards and open source Cloud Management Frameworks and offers to its users IaaS, PaaS and SaaS capabilities and interfaces tuned towards the needs of users in research and education. The federation enables scientific data, workloads, simulations and services to span across multiple administrative locations, allowing researchers and educators to access and exploit the distributed resources as an integrated system. The EGI Federated Cloud collaboration established a user support model and a training infrastructure to raise visibility of this service within European scientific communities with the overarching goal to increase adoption and, ultimately increase the usage of e-infrastructures for the benefit of the whole European Research Area. The paper describes this scalable user support and training infrastructure models. The training infrastructure is built on top of the production sites to reduce costs and increase its sustainability. Appropriate design solutions were implemented to reduce the security risks due to the cohabitation of production and training resources on the same sites. The EGI Federated Cloud educational program foresees different kind of training events from basic tutorials to spread the knowledge of this new infrastructure to events devoted to specific scientific disciplines teaching how to use tools already integrated in the infrastructure with the assistance of experts identified in the EGI community. The main success metric of this educational program is the number of researchers willing to try the Federated Cloud, which are steered into the EGI world by the EGI Federated Cloud Support Team through a formal process that brings them from the initial tests to fully exploit the production resources. © 2015 IEEE

Phylogenetic quantification of intra-tumour heterogeneity.

Intra-tumour genetic heterogeneity is the result of ongoing evolutionary change within each cancer. The expansion of genetically distinct sub-clonal populations may explain the emergence of drug resistance, and if so, would have prognostic and predictive utility. However, methods for objectively quantifying tumour heterogeneity have been missing and are particularly difficult to establish in cancers where predominant copy number variation prevents accurate phylogenetic reconstruction owing to horizontal dependencies caused by long and cascading genomic rearrangements. To address these challenges, we present MEDICC, a method for phylogenetic reconstruction and heterogeneity quantification based on a Minimum Event Distance for Intra-tumour Copy-number Comparisons. Using a transducer-based pairwise comparison function, we determine optimal phasing of major and minor alleles, as well as evolutionary distances between samples, and are able to reconstruct ancestral genomes. Rigorous simulations and an extensive clinical study show the power of our method, which outperforms state-of-the-art competitors in reconstruction accuracy, and additionally allows unbiased numerical quantification of tumour heterogeneity. Accurate quantification and evolutionary inference are essential to understand the functional consequences of tumour heterogeneity. The MEDICC algorithms are independent of the experimental techniques used and are applicable to both next-generation sequencing and array CGH data.This is the final published version. It was originally published by PLoS in PLoS Computational Biology here: http://www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1003535

The rise of fully turbulent flow

Over a century of research into the origin of turbulence in wallbounded shear flows has resulted in a puzzling picture in which turbulence appears in a variety of different states competing with laminar background flow. At slightly higher speeds the situation changes distinctly and the entire flow is turbulent. Neither the origin of the different states encountered during transition, nor their front dynamics, let alone the transformation to full turbulence could be explained to date. Combining experiments, theory and computer simulations here we uncover the bifurcation scenario organising the route to fully turbulent pipe flow and explain the front dynamics of the different states encountered in the process. Key to resolving this problem is the interpretation of the flow as a bistable system with nonlinear propagation (advection) of turbulent fronts. These findings bridge the gap between our understanding of the onset of turbulence and fully turbulent flows.Comment: 31 pages, 9 figure

Translocation of PEGylated quantum dots across rat alveolar epithelial cell monolayers

Farnoosh Fazlollahi1,8, Arnold Sipos1,2, Yong Ho Kim1,2, Sarah F Hamm-Alvarez6, Zea Borok1–3, Kwang-Jin Kim1,2,5–7, Edward D Crandall1,2,4,8 1Will Rogers Institute Pulmonary Research Center, 2Department of Medicine, 3Department of Biochemistry and Molecular Biology, 4Department of Pathology, 5Department of Physiology and Biophysics, 6Department of Pharmacology and Pharmaceutical Sciences, 7Department of Biomedical Engineering, 8Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA, USA Background: In this study, primary rat alveolar epithelial cell monolayers (RAECM) were used to investigate transalveolar epithelial quantum dot trafficking rates and underlying transport mechanisms. Methods: Trafficking rates of quantum dots (PEGylated CdSe/ZnS, core size 5.3 nm, hydrodynamic size 25 nm) in the apical-to-basolateral direction across RAECM were determined. Changes in bioelectric properties (ie, transmonolayer resistance and equivalent active ion transport rate) of RAECM in the presence or absence of quantum dots were measured. Involvement of endocytic pathways in quantum dot trafficking across RAECM was assessed using specific inhibitors (eg, methyl-ß-cyclodextrin, chlorpromazine, and dynasore for caveolin-, clathrin-, and dynamin-mediated endocytosis, respectively). The effects of lowering tight junctional resistance on quantum dot trafficking were determined by depleting Ca2+ in apical and basolateral bathing fluids of RAECM using 2 mM EGTA. Effects of temperature on quantum dot trafficking were studied by lowering temperature from 37°C to 4°C. Results: Apical exposure of RAECM to quantum dots did not elicit changes in transmonolayer resistance or ion transport rate for up to 24 hours; quantum dot trafficking rates were not surface charge-dependent; methyl-ß-cyclodextrin, chlorpromazine, and dynasore did not decrease quantum dot trafficking rates; lowering of temperature decreased transmonolayer resistance by approximately 90% with a concomitant increase in quantum dot trafficking by about 80%; and 24 hours of treatment of RAECM with EGTA decreased transmonolayer resistance by about 95%, with increased quantum dot trafficking of up to approximately 130%. Conclusion: These data indicate that quantum dots do not injure RAECM and that quantum dot trafficking does not appear to take place via endocytic pathways involving caveolin, clathrin, or dynamin. We conclude that quantum dot translocation across RAECM takes place via both transcellular and paracellular pathways and, based on comparison with our prior studies, interactions of nanoparticles with RAECM are strongly dependent on nanoparticle composition and surface properties. Keywords: alveolar epithelial barrier, transport, paracellular pathways, endocytosi

Evolution of genes and repeats in the Nimrod superfamily

The recently identified Nimrod superfamily is characterized by the presence of a special type of EGF repeat, the NIM repeat, located right after a typical CCXGY/W amino acid motif. On the basis of structural features, nimrod genes can be divided into three types. The proteins encoded by Draper-type genes have an EMI domain at the N-terminal part and only one copy of the NIM motif, followed by a variable number of EGF-like repeats. The products of Nimrod B-type and Nimrod C-type genes (including the eater gene) have different kinds of N-terminal domains, and lack EGF-like repeats but contain a variable number of NIM repeats. Draper and Nimrod C-type (but not Nimrod B-type) proteins carry a transmembrane domain. Several members of the superfamily were claimed to function as receptors in phagocytosis and/or binding of bacteria, which indicates an important role in the cellular immunity and the elimination of apoptotic cells. In this paper, the evolution of the Nimrod superfamily is studied with various methods on the level of genes and repeats. A hypothesis is presented in which the NIM repeat, along with the EMI domain, emerged by structural reorganizations at the end of an EGF-like repeat chain, suggesting a mechanism for the formation of novel types of repeats. The analyses revealed diverse evolutionary patterns in the sequences containing multiple NIM repeats. Although in the Nimrod B and Nimrod C proteins show characteristics of independent evolution, many internal NIM repeats in Eater sequences seem to have undergone concerted evolution. An analysis of the nimrod genes has been performed using phylogenetic and other methods and an evolutionary scenario of the origin and diversification of the Nimrod superfamily is proposed. Our study presents an intriguing example how the evolution of multigene families may contribute to the complexity of the innate immune response