Patients After the Fontan Insights From Computational Fluid Dynamics

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Geomorphological mapping with a small unmanned aircraft system (sUAS): feature detection and accuracy assessment of a photogrammetrically-derived digital terrain model

Sherpa Romeo green journal. Permission to archive accepted author manuscript.Small unmanned aircraft systems (sUAS) are a relatively new type of aerial platform for acquiring high-resolution remote sensing measurements of Earth surface processes and landforms. However, despite growing application there has been little quantitative assessment of sUAS performance. Here we present results from a field experiment designed to evaluate the accuracy of a photogrammetrically-derived digital terrain model (DTM) developed from imagery acquired with a low-cost digital camera onboard an sUAS. We also show the utility of the highresolution (0.1 m) sUAS imagery for resolving small-scale biogeomorphic features. The experiment was conducted in an area with active and stabilized aeolian landforms in the southern Canadian Prairies. Images were acquired with a Hawkeye RQ-84Z Aerohawk fixed-wing sUAS. A total of 280 images were acquired along 14 flight lines, covering an area of 1.95 km2. The survey was completed in 4.5 hours, including GPS surveying, sUAS setup and flight time. Standard image processing and photogrammetric techniques were used to produce a 1 m resolution DTM and a 0.1 m resolution orthorectified image mosaic. The latter revealed previously un-mapped bioturbation features. The vertical accuracy of the DTM was evaluated with 99 Real-Time Kinematic GPS points, while 20 of these points were used to quantify horizontal accuracy. The horizontal root mean squared error (RMSE) of the orthoimage was 0.18 m, while the vertical RMSE of the DTM was 0.29 m, which is equivalent to the RMSE of a bare earth LiDAR DTM for the same site. The combined error from both datasets was used to define a threshold of the minimum elevation difference that could be reliably attributed to erosion or deposition in the seven years separating the sUAS and LiDAR datasets. Overall, our results suggest that sUAS-acquired imagery may provide a low-cost, rapid, and flexible alternative to airborne LiDAR for geomorphological mapping.Ye

Lipidoid-Coated Iron Oxide Nanoparticles for Efficient DNA and siRNA delivery

The safe, targeted and effective delivery of gene therapeutics remains a significant barrier to their broad clinical application. Here we develop a magnetic nucleic acid delivery system composed of iron oxide nanoparticles and cationic lipid-like materials termed lipidoids. Coated nanoparticles are capable of delivering DNA and siRNA to cells in culture. The mean hydrodynamic size of these nanoparticles was systematically varied and optimized for delivery. While nanoparticles of different sizes showed similar siRNA delivery efficiency, nanoparticles of 50–100 nm displayed optimal DNA delivery activity. The application of an external magnetic field significantly enhanced the efficiency of nucleic acid delivery, with performance exceeding that of the commercially available lipid-based reagent, Lipofectamine 2000. The iron oxide nanoparticle delivery platform developed here offers the potential for magnetically guided targeting, as well as an opportunity to combine gene therapy with MRI imaging and magnetic hyperthermia.National Heart, Lung, and Blood InstituteNational Institutes of Health (U.S.) (Program of Excellence in Nanotechnology (PEN) Award, Contract #HHSN268201000045C

PEG–Polypeptide Block Copolymers as pH-Responsive Endosome-Solubilizing Drug Nanocarriers

Herein we report the potential of click chemistry-modified polypeptide-based block copolymers for the facile fabrication of pH-sensitive nanoscale drug delivery systems. PEG–polypeptide copolymers with pendant amine chains were synthesized by combining N-carboxyanhydride-based ring-opening polymerization with post-functionalization using azide–alkyne cycloaddition. The synthesized block copolymers contain a polypeptide block with amine-functional side groups and were found to self-assemble into stable polymersomes and disassemble in a pH-responsive manner under a range of biologically relevant conditions. The self-assembly of these block copolymers yields nanometer-scale vesicular structures that are able to encapsulate hydrophilic cytotoxic agents like doxorubicin at physiological pH but that fall apart spontaneously at endosomal pH levels after cellular uptake. When drug-encapsulated copolymer assemblies were delivered systemically, significant levels of tumor accumulation were achieved, with efficacy against the triple-negative breast cancer cell line, MDA-MB-468, and suppression of tumor growth in an in vivo mouse model.Novartis Institutes of Biomedical ResearchNational Institutes of Health (U.S.) (Centers for Cancer Nanotechnology Excellence Grant P30 CA14051)National Institutes of Health (U.S.) (Centers for Cancer Nanotechnology Excellence Grant 5 U54 CA151884-02)National Science Foundation (U.S.). Graduate Research FellowshipNatural Sciences and Engineering Research Council of Canada (Postdoctoral Fellowship

From Indymedia to Anonymous: rethinking action and identity in digital cultures

The period following the social mobilizations of 2011 has seen a renewed focus on the place of communication in collective action, linked to the increasing importance of digital communications. Framed in terms of personalized ‘connective action’ or the social morphology of networks, these analyses have criticized previously dominant models of ‘collective identity’, arguing that collective action needs to be understood as ‘digital networking’. These influential approaches have been significantly constructed as a response to models of communication and action evident in the rise of Independent Media Centres in the period following 1999. After considering the rise of the ‘digital networking’ paradigm linked to analyses of Indymedia, this article considers the emergence of the internet-based collaboration known as Anonymous, focusing on its origins on the 4chan manga site and its 2008 campaign against Scientology, and also considers the ‘I am the 99%’ microblog that emerged as part of the Occupy movement. The emergence of Anonymous highlights dimensions of digital culture such as the ephemeral, the importance of memes, an ethic of lulz, the mask and the grotesque. These forms of communication are discussed in the light of dominant attempts to shape digital space in terms of radical transparency, the knowable and the calculable. It is argued that these contrasting approaches may amount to opposing social models of an emerging information society, and that the analysis of contemporary conflicts and mobilizations needs to be alert to novel forms of communicative practice at work in digital cultures today

Dioctadecyldimethylammonium:monoolein nanocarriers for efficient in vitro gene silencing

This study describes a novel liposomal formulation for siRNA delivery, based on the mixture of the neutral lipid monoolein (MO) and cationic lipids of the dioctadecyldimethylammonium (DODA) family. The cationic lipids dioctadecyldimethylammonium bromide (DODAB) and chloride (DODAC) were compared in order to identify which one will most efficiently induce gene silencing. MO has a fluidizing effect on DODAC and DODAB liposomes, although it was more homogeneously distributed in DODAC bilayers. All MO-based liposomal formulations were able to efficiently encapsulate siRNA. Stable lipoplexes of small size (100-160 nm) with a positive surface charge (>+45 mV) were formed. A more uniform MO incorporation in DODAC:MO may explain an increase of the fusogenic potential of these liposomes. The siRNA-lipoplexes were readily internalized by human nonsmall cell lung carcinoma (H1299) cells, in an energy dependent process. DODAB:MO nanocarriers showed a higher internalization efficiency in comparison to DODAC:MO lipoplexes, and were also more efficient in promoting gene silencing. MO had a similar gene silencing ability as the commonly used helper lipid 1,2-dioleyl-3-phosphatidylethanolamine (DOPE), but with much lower cytotoxicity. Taking in consideration all the results presented, DODAB:MO liposomes are the most promising tested formulation for systemic siRNA delivery.This work was supported by FEDER through POFC - COMPETE and by national funds from FCT through the projects PEst-C/BIA/UI4050/2011 (CBM.A), PEst-C/FIS/UI0607/2011 (CFUM), and PTDC/QUI/69795/2006, while Ana Oliveira holds scholarship SFRH/BD/68588/2010. Eloi Feitosa thanks FAPESP (2011/03566-0) and CNPq (303030/2012-7), and Renata D. Adati thanks FAPESP for scholarship (2011/07414-0). K. Raemdonck is a postdoctoral fellow of the Research Foundation - Flanders (FWO-Vlaanderen). We acknowledge NanoDelivery-I&D em Bionanotecnologia, Lda. for access to their equipment