Signs Workshop: the importance of natural gestures in the promotion of early communication skills of children with developmental disabilities

This article emphasises the importance of natural gestures and describes the framework and the development process of the “Signs Workshop” CD-ROM, which is a multimedia application for the promotion of early communication skills of children with developmental disabilities. Signs Workshop CD-ROM was created in the scope of Down’s Comm Project, which was financed by the Calouste Gulbenkian Foundation, and is the result of a partnership between UNICA (Communication and Arts Research Unit of the University of Aveiro) and the Portuguese Down Syndrome Association (APPT21/Differences)

On the nature of macroradicals formed upon radiolysis of aqueous poly(N-vinylpyrrolidone) solutions

In this work we have explored the nature of macroradicals formed upon radiolysis of aqueous poly(N-vinylpyrrolidone) (PVP) solutions using pulse radiolysis, density functional theory (DFT) and literature data. On the basis of literature data on site-specific kinetics of hydrogen abstraction from simple amides and spectra corresponding to specific radical sites on the same amides we have assessed the distribution of H-atom abstraction by \u2022OH radicals from different positions on the pyrrolidone ring and the polymer backbone. Pulse radiolysis experiments performed at different doses per pulse and different PVP concentrations demonstrate that the H-abstracting radiolysis products are not quantitatively scavenged by the polymer when the dose per pulse exceeds 4840 Gy. The implications of this are discussed in the context of radical-initiated crosslinking reactions. At a mass fraction of 0.1% PVP and doses per pulse ranging from 7 Gy to 117 Gy, the overall radical decay observed at 390 nm follows second order kinetics with rate constants on the order of 109 dm3 mol-1 s-1

Highly-parallelized simulation of a pixelated LArTPC on a GPU

The rapid development of general-purpose computing on graphics processing units (GPGPU) is allowing the implementation of highly-parallelized Monte Carlo simulation chains for particle physics experiments. This technique is particularly suitable for the simulation of a pixelated charge readout for time projection chambers, given the large number of channels that this technology employs. Here we present the first implementation of a full microphysical simulator of a liquid argon time projection chamber (LArTPC) equipped with light readout and pixelated charge readout, developed for the DUNE Near Detector. The software is implemented with an end-to-end set of GPU-optimized algorithms. The algorithms have been written in Python and translated into CUDA kernels using Numba, a just-in-time compiler for a subset of Python and NumPy instructions. The GPU implementation achieves a speed up of four orders of magnitude compared with the equivalent CPU version. The simulation of the current induced on 10^3 pixels takes around 1 ms on the GPU, compared with approximately 10 s on the CPU. The results of the simulation are compared against data from a pixel-readout LArTPC prototype

Early Events in Ionic Liquid Radiation Chemistry

Ionic liquids are interesting and useful materials whose solvation time scales are up to thousands of times longer than in conventional solvents. The extended lifetimes of pre-solvated electrons and other energetic species in ionic liquids has profound consequences for the radiolytic product distributions and reactivity patterns. We use a newly developed, multiplexed variation of pulse-probe spectroscopy to measure the kinetics of the early dynamical and reactive events in ionic liquids

Metformin and DPP-4 inhibitor differentially modulate the intestinal microbiota and plasma metabolome of metabolically dysfunctional mice

Background Recent evidence indicates that the gut microbiota is altered considerably by a variety of commonly prescribed medications. This study assessed the impact of two antidiabetic therapeutics on the gut microbiota and markers of cardiometabolic disease in metabolically dysfunctional mice. Materials & Methods C57BL/6 mice were fed a high-fat diet for 24-weeks while receiving one of two antidiabetic therapeutics - metformin or DPP-4 inhibitor, PKF-275-055 - for the final 12 weeks. Mice were assessed for weight gain, glucose and cholesterol metabolism, and adiposity. In addition, caecal microbiota was analysed by 16S compositional sequencing and plasma metabolome was analysed by LC-MS/MS. Results Both therapeutics had similar metabolic effects, attenuating mesenteric adiposity, improving cholesterol metabolism and insulin sensitivity. However, multivariate analyses of microbiota and metabolomics data revealed clear divergence of the therapeutic groups. While both metformin and PKF-275-055 mice displayed significantly decreased Firmicutes/Bacteroidetes ratios, only metformin harboured metabolic health-associated Akkermansia, Parabacteroides and Christensenella. Paradoxically, metformin also reduced α-diversity, a metric frequently associated with host metabolic fitness. PKF-275-055 mice displayed elevated levels of butyrate-producing Ruminococcus and acetogen Dorea, with reduced levels of certain plasma sphingomyelin, phosphatidylcholine and lysophosphatidylcholine entities. In turn, metformin reduced levels of acylcarnitines, a functional group associated with systemic metabolic dysfunction. Finally, several associations were identified between metabolites and altered taxa. Conclusions This study represents the first direct comparison of the microbiota-modifying effects of metformin and a DPP-4 inhibitor, and proposes several putative microbial targets both in terms of novel therapeutic development and adverse effect prevention

Metformin and a DPP-4-inhibitor differentially modulate the microbiome and metabolome of Metabolic Syndrome mice

This study assessed the impact of 2 anti-diabetic therapies on the gut microbiome and markers of cardiometabolic disease risk in mice. We employed a metabolic syndrome model in which C57BL/6 mice were fed a high-fat diet for 25 weeks while receiving 1 of 2 antidiabetic therapeutics—metformin or a DPP-4 inhibitor (PKF-275- 055)—for the final 12 weeks. Animals were monitored for weight gain, as well as glucose/cholesterol metabolism. In addition, adiposity was investigated at dissection, cecal microbiome was analyzed by 16S compositional sequencing and serum was analyzed by liquid chromatography-tandem mass spectrometry. Both therapeutics significantly improved glucose/cholesterol metabolism, attenuated weight gain and mesenteric adipose accumulation. However, multivariate analyses of microbiome and metabolomics data revealed clear profile separation of the therapeutic groups. While both metformin (0.78; p<0.05) and PKF-275-055 (1.00; p<0.05) mice displayed significantly decreased Firmicutes/Bacteroidetes ratios, only metformin animals harboured metabolic health-promoting Akkermansia (3.4%; p<0.0001). Intriguingly, PKF-275-055 mice displayed elevated levels of the butyrate-producing Rumminococcus (2.0%; p<0.05) and the acetogen Dorea (0.95%; p<0.05). We identified reduced levels of certain sphingomyelin, phosphatidylcholine and lysophosphatidylcholine entities within serum of the PKF-275- 055 group when compared to metformin and control. Conversely, metformin mice presented primarily with reduced levels of acylcarnitines, a functional group that has correlated with obesity, insulin resistance and systemic metabolic dysfunction in humans. This study adds weight to the hypothesis that some anti-diabetic therapeutics act in part through manipulation of the gut microbiome. Additionally, we identify several metabolites that may be of central importance in the mechanisms of metformin and PKF-275-055