A Framework for Directional and Higher-Order Reconstruction in Photoacoustic Tomography

Photoacoustic tomography is a hybrid imaging technique that combines high optical tissue contrast with high ultrasound resolution. Direct reconstruction methods such as filtered backprojection, time reversal and least squares suffer from curved line artefacts and blurring, especially in case of limited angles or strong noise. In recent years, there has been great interest in regularised iterative methods. These methods employ prior knowledge on the image to provide higher quality reconstructions. However, easy comparisons between regularisers and their properties are limited, since many tomography implementations heavily rely on the specific regulariser chosen. To overcome this bottleneck, we present a modular reconstruction framework for photoacoustic tomography. It enables easy comparisons between regularisers with different properties, e.g. nonlinear, higher-order or directional. We solve the underlying minimisation problem with an efficient first-order primal-dual algorithm. Convergence rates are optimised by choosing an operator dependent preconditioning strategy. Our reconstruction methods are tested on challenging 2D synthetic and experimental data sets. They outperform direct reconstruction approaches for strong noise levels and limited angle measurements, offering immediate benefits in terms of acquisition time and quality. This work provides a basic platform for the investigation of future advanced regularisation methods in photoacoustic tomography.Comment: submitted to "Physics in Medicine and Biology". Changes from v1 to v2: regularisation with directional wavelet has been added; new experimental tests have been include

QRTEngine: An easy solution for running online reaction time experiments using Qualtrics

Performing online behavioral research is gaining increased popularity among researchers in psychological and cognitive science. However, the currently available methods for conducting online reaction time experiments are often complicated and typically require advanced technical skills. In this article, we introduce the Qualtrics Reaction Time Engine (QRTEngine), an open-source JavaScript engine that can be embedded in the online survey development environment Qualtrics. The QRTEngine can be used to easily develop browser-based online reaction time experiments with accurate timing within current browser capabilities, and it requires only minimal programming skills. After introducing the QRTEngine, we briefly discuss how to create and distribute a Stroop task. Next, we describe a study in which we investigated the timing accuracy of the engine under different processor loads using external chronometry. Finally, we show that the QRTEngine can be used to reproduce classic behavioral effects in three reaction time paradigms: a Stroop task, an attentional blink task, and a masked-priming task. These findings demonstrate that QRTEngine can be used as a tool for conducting online behavioral research even when this requires accurate stimulus presentation times

Acrylamides with hydrolytically labile carbonate ester side chains as versatile building blocks for well-defined block copolymer micelles via RAFT polymerization

En route towards improved delivery systems for targeted chemotherapy, we propose a straightforward approach for the hydrophobic modification of the acrylamide N-(2-Hydroxyethyl) acrylamide (HEAm). An ethyl or benzyl group was introduced via a hydrolytically sensitive carbonate ester yielding HEAm-EC and HEAm-BC, respectively. Block copolymers of HEAm, respectively PEG and HEAm-EC or HEAm-BC were successfully synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization, obtaining a library of well-defined block copolymers with different degrees of polymerization (DP). To further explore the versatility of our approach in terms of polymer synthesis, self-assembly, drug solubilization and in vitro cell interaction, polyethylene glycol (PEG) and polyHEAm as hydrophilic polymer blocks were compared. The block copolymers formed micellar nanoparticles (10-100 nm) in PBS and could efficiently solubilize hydrophobic dyes and anti-cancer drugs. Benzyl carbonate ester side chains increased micellar stability and drug loading capacity. Moreover, PEG as hydrophilic block showed in comparison to HEAm more promising results concerning both colloidal stability and drug loading capacity. Confocal microscopy showed that the micelles could efficiently deliver a hydrophobic dye inside the cells. Finally, we also demonstrated efficient formulation of the anti-cancer drug paclitaxel with an in vitro cancer cell killing performance comparable or even better than the two commercial PTX nano-formulations Abraxane and Genexol-PM at equal drug dose. In conclusion, modification of HEAm through carbonate linkages offers a versatile platform for the design of degradable polymers with potential for biomedical applications

Biodegradable Poly(2-Dimethylamino Ethylamino)Phosphazene for In Vivo Gene Delivery to Tumor Cells. Effect of Polymer Molecular Weight

Purpose. Previously, we have shown that complexes of plasmid DNA with the biodegradable polymer poly(2-dimethylamino ethylamino)phosphazene (p(DMAEA)-ppz) mediated tumor selective gene expression after intravenous administration in mice. In this study, we investigated the effect of p(DMAEA)-ppz molecular weight on both in vitro and in vivo tumor transfection, as well as on complex induced toxicity. Materials and Methods. p(DMAEA)-ppz with a broad molar mass distribution was fractionated by preparative size exclusion chromatography. Polyplexes consisting of plasmid DNA and the collected polymer fractions were tested for biophysical properties, (cyto)toxicity and transfection activity. Results. Four p(DMAEA)-ppz fractions were collected with weight average molecular weights ranging from 130 to 950 kDa, and with narrow molecular mass distributions (Mw/Mn from 1.1 to 1.3). At polymer-to-DNA (N/P) ratios above 6, polyplexes based on these polymers were all positively charged (zeta potential 25–29 mV), and had a size of 80–90 nm. The in vitro cytotoxicity of the polyplexes positively correlated with polymer molecular weight. The in vitro transfection activity of the different polyplexes depended on their N/P ratio, and was affected by the degree of cytotoxicity, as well as the colloidal stability of the different polyplexes. Intravenous administration of polyplexes based on the high molecular weight polymers led to apparent toxicity, as a result of polyplex-induced erythrocyte aggregation. On the other hand, administration of polyplexes based on low molecular weight p(DMAEA)-ppz_s (Mw130 kDa) did not show signs of toxicity and resulted in tumor selective gene expression. Conclusion. Polymer molecular weight fractionation enabled us to optimize the transfection efficiency/ toxicity ratio of p(DMAEA)-ppz polyplexes for in vitro and in vivo tumor transfection. KEY WORDS: biodegradable; cationic polymer; DNA; molecular weight; tumor gene delivery

Mechanistic Study on the Degradation of Hydrolysable Core-Crosslinked Polymeric Micelles

Core-crosslinked polymeric micelles (CCPMs) are an attractive class of nanocarriers for drug delivery. Two crosslinking approaches to form CCPMs exist: either via a low-molecular-weight crosslinking agent to connect homogeneous polymer chains with reactive handles or via cross-reactive handles on polymers to link them to each other (complementary polymers). Previously, CCPMs based on methoxy poly(ethylene glycol)- b-poly[ N-(2-hydroxypropyl) methacrylamide-lactate] (mPEG- b-PHPMAmLac n ) modified with thioesters were crosslinked via native chemical ligation (NCL, a reaction between a cysteine residue and thioester resulting in an amide bond) using a bifunctional cysteine containing crosslinker. These CCPMs are degradable under physiological conditions due to hydrolysis of the ester groups present in the crosslinks. The rapid onset of degradation observed previously, as measured by the light scattering intensity, questions the effectiveness of crosslinking via a bifunctional agent. Particularly due to the possibility of intrachain crosslinks that can occur using such a small crosslinker, we investigated the degradation mechanism of CCPMs generated via both approaches using various analytical techniques. CCPMs based on complementary polymers degraded slower at pH 7.4 and 37 °C than CCPMs with a crosslinker (the half-life of the light scattering intensity was approximately 170 h versus 80 h, respectively). Through comparative analysis of the degradation profiles of the two different CCPMs, we conclude that partially ineffective intrachain crosslinks are likely formed using the small crosslinker, which contributed to more rapid CCPM degradation. Overall, this study shows that the type of crosslinking approach can significantly affect degradation kinetics, and this should be taken into consideration when developing new degradable CCPM platforms

Making justice more accessible

From the point of view of the Citizen, Justice is not always readily accessible. Either because it is a lengthy process, potentially expensive, sometimes unclear or simply scary, people will often avoid or withdraw from a judicial process, especially in those cases that involve relatively small amounts. This results in the giving up of a basic right, with the potential loss of rightful benefits. In this paper we briefly analyze the main aspects that impair access to Justice nowadays. We then move on to look at recent technological developments in the field of Online Dispute Resolution to argue that these can, in the near future, have a significant role in improving access to Justice. Specifically, we analyze the UMCourt Conflict Resolution Framework, developed by our research team, and address the different dimensions in which such tools contribute to make Justice more accessible, namely through better access to useful information, support in decision-making or more cost-effective processes.Development Fund through the COMPETE Programme (operational programme for competitiveness) and by National Funds through the FCT - Fundação para a Ciência e a Tecnologia (Portuguese Foundation for Science and Technology) within projects FCOMP-01-0124-FEDER-028980 (PTDC/EEISII/1386/ 2012) and PEst-OE/EEI/UI0752/201

Кіноніми Кіровоградщини: особливості вибору кличок та способи їх творення

Стаття присвячена вивченню особливостей української кінонімії. Основну увагу зосереджено на дослідженні процесу номінації та способів словотворення кличок собак. Окремо розглянуто офіційні назви тварин, які мають родослівну.Статья посвящена изучению особенностей украинской кинонимии. Основное внимание сосредоточено на изучении процесса номинации и способах словообразования кличек собак. Отдельно рассмотрены официальные названия собак, имеющих родословную.The article is devoted to the research of the peculiarities of Ukrainian cynonymy. Most attention is taid to the research of the process of nomination and to the ways of formation of dogs' names. Special consideration is given to the official names of the animals with genealogy