1,656 research outputs found

    Linking micellar phases to peptide supramolecular hydrogels

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    Supramolecular peptide solutions and hydrogels are pathway-dependent multi-scale structured materials. This Thesis investigates three major aspects that impact on the self-assembly pathway. Firstly, the importance of the kinetics is investigated in the dipeptide gelators self-assembly pathway. Second, a proposed gelator-solvent phase diagram suggested a worm-like phase and an entangled worm-like micellar phase for N-protected dipeptide gelators. Thirdly, some links between hydrogel network structure and gelator solution phase properties were identified over multiple length scales for a particular class of peptide-based low molecular weight gelators (LMWG). These links allows some predictions to be made on the mechanical properties of peptide hydrogels triggered by salts based on the solution phase properties. A new method based on carbon dioxide acidification of specific gelator solutions formed unusual membrane hydrogels. This unusual heterogeneous hydrogel formation occured when the gelator’s apparent pKa was a pH unit close to the final pH and the starting gelator solution did not have a high viscous solution at the high pH (typically above pH 10.5). This membrane hydrogel phase had similar viscoelastic properties to the intermediary transition state previously found with pH-switch methods in bulk hydrogel formation (from high to low pH). The carbon dioxide method was also capable of forming bulk hydrogels for gelators with apparent pKa significantly above the final pH. This method was thoroughly investigated with 6-bromo-2-naphthalene-alanine-valine (BrNapAV). This research also focused on the first detailed phase diagram of an individual gelator solution phase, in this case of 2-naphthalene-diphenylalanine (2NapFF), an N-protected dipeptides over three orders of magnitude in concentration and between temperatures of 15 °C and 45 °C. The solution phase of 2NapFF was found to go through a range of micellar transformations with an increase in concentration from free-surfactant, spherical aggregate phase, worm-like micellar phase and packed worm-like micellar phase. The critical micellar concentrations (cmc’s), at which phase transitions occur, and the minimum gelator concentrations (mgc) with calcium nitrate salt solutions were found for 2NapFF. The common trends in the 2NapFF solution phase were extended to a library of 17 gelators. It was found that the 2NapFF peptide hydrogel phase is structurally connected to the corresponding solution phase. This allows prediction of the final properties of the Calcium-hydrogels (Ca-hydrogels) from the starting conditions of the corresponding peptide surfactant solutions, based on consideration of the solution phase diagram and self-assembly process. These results showed that the 2NapFF solutions could form Ca-hydrogels in a concentration from 0.02 wt% to 1.0 wt%, corresponding to three orders of magnitude in complex modulus. It was also found that the presence of worm like micelles in the solution phase was linked to mechanically stronger Ca-hydrogels. The gelation by addition of the calcium salt shifted the worm-like micellar concentration region and changed the microstructure to increase packing. The concentration was found to correlate with the mechanical properties with an exponential function with a 1.99 coefficient, typical for cross-linked networks and biopolymer gels. Finally, four types of microscopy techniques were used to conduct a structural analysis on multiple length scales with: optical microscopy, scanning electron microscopy, confocal microscopy and atomic force microscopy. A new open-source fibre tracking software was used on microscopy images and the structural parameters obtained were characterised by: fibre and worm diameter, bundle diameter, persistence length, contour length, nematic order, and type of fibre. These results suggest that microscopy interpretation of hierarchical structured materials has to be done for a specific length scale image, only relate to the features of length scale covered from the size that image to the resolution of the image. The Ca-hydrogel nanofibres in between a concentration of 0.01 and 1.0 wt% had the main nanofibre width of 20.5 ± 4.3 nm measured by SEM. There were also detectable fibres with an extended width from tenths of nanometres to few micrometres. Laser Scanning Confocal Microscopy (LSCM) measurements allowed a microstructural snapshot of the Ca-hydrogels. Additionally, LSCM identified that in solution phase no correlation is observable between the microstructure (persistence length of the fibre bundles) and the complex modulus G*, while for the Ca-hydrogel phase, the persistence length of the nanofibre bundles increases with the increase G*. The worm-like structures were found to be highly oriented in the solution phase across concentrations from 0.1 wt% to 1.0 wt%. In the Ca-hydrogel phase, the degree or oriented structures increased from 0.05 wt% to 1.0 wt%

    A comparison between body weight-supported treadmill training and conventional over-ground training in dogs with incomplete spinal cord injury

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    Research Areas: Veterinary SciencesIn human medicine there was no evidence registered of a significant difference in recovery between body weight-supported treadmill training (BWSTT) and conventional over-ground (COGI). There isn’t any similar study in veterinary medicine. Thus, this study aimed to compare the locomotor recovery obtained in incomplete SCI (T11–L3 Hansen type I) post-surgical dogs following BWSTT or COGI protocols, describing their evolution during 7 weeks in regard to OFS classifications. At admission, dogs were blindly randomized in two groups but all were subjected to the same protocol (underwater treadmill training) for the first 2 weeks. After, they were divided in the BWSTT group (n = 10) and the COGI group (n = 10) for the next 2 weeks, where they performed different training. In both groups locomotor training was accompanied by functional electrical stimulation (FES) protocols. Results reported statistically significant differences between all OFS evaluations time-points (p < 0.001) and between the two groups (p < 0.001). In particular with focus on T1 to T3 a two-way repeated measures ANOVA was performed and similar results were obtained (p = 0.007). Functional recovery was achieved in 90% (17/19) of all dogs and 100% recovered bladder function. The BWSTT group showed 100% (10/10) recovery within a mean time of 4.6 weeks, while the COGI group had 78% (7/9) within 6.1 weeks. Therefore, BWSTT leads to a faster recovery with a better outcome in general.info:eu-repo/semantics/publishedVersio

    Treatable Traits in COPD - A Proposed Approach

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    The well-recognized individual heterogeneity within COPD patients has led to a growing interest in greater personalization in the approach of these patients. Thus, the treatable traits strategy has been proposed as a further step towards precision medicine in the management of chronic airway disease, both in stable phase and acute exacerbations. The aim of this paper is to perform a critical review on the treatable traits strategy and propose a guide to approach COPD patients in the light of this new concept. An innovative stepwise approach is proposed - a multidisciplinary model based on two distinct phases, with the potential to be implemented in both primary care and hospital settings. The first phase is the initial and focused assessment of a selected subset of treatable traits, which should be addressed in all COPD patients in both settings (primary care and hospital). As some patients may present with advanced disease at diagnosis or may progress despite this initial treatment requiring a more specialized assessment, they should progress to a second phase, in which a broader approach is recommended. Beyond stable COPD, we explore how the treatable traits strategy may be applied to reduce the risk of future exacerbations and improve the management of COPD exacerbations. Since many treatable traits have already been related to exacerbation risk, the strategy proposed here represents an opportunity to be proactive. Although it still lacks prospective validation, we believe this is the way forward for the future of the COPD approach.info:eu-repo/semantics/publishedVersio

    Spinal locomotion in cats following spinal cord injury : a prospective study

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    Research Areas: Agriculture ; Veterinary SciencesThis article aimed to evaluate the safety and efficacy of intensive neurorehabilitation in paraplegic cats, with no deep pain perception (grade 0 on the modified Frankel scale), with more than three months of injury. Nine cats, admitted to the Arrábida Veterinary Hospital/Arrábida Animal Rehabilitation Center (CRAA), were subjected to a 12-week intensive functional neurorehabilitation protocol, based on ground and underwater treadmill locomotor training, electrostimulation, and kinesiotherapy exercises, aiming to obtain a faster recovery to ambulation and a modulated locomotor pattern of flexion/extension. Of the nine cats that were admitted in this study, 56% (n = 5) recovered from ambulation, 44% of which (4/9) did so through functional spinal locomotion by reflexes, while one achieved this through the recovery of deep pain perception. These results suggest that intensive neurorehabilitation can play an important role in ambulation recovery, allowing for a better quality of life and well-being, which may lead to a reduction in the number of euthanasia procedures performed on paraplegic animals.info:eu-repo/semantics/publishedVersio

    Learning to segment when experts disagree

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    Recent years have seen an increasing use of supervised learning methods for segmentation tasks. However, the predictive performance of these algorithms depend on the quality of labels, especially in medical image domain, where both the annotation cost and inter-observer variability are high. In a typical annotation collection process, different clinical experts provide their estimates of the “true” segmentation labels under the influence of their levels of expertise and biases. Treating these noisy labels blindly as the ground truth can adversely affect the performance of supervised segmentation models. In this work, we present a neural network architecture for jointly learning, from noisy observations alone, both the reliability of individual annotators and the true segmentation label distributions. The separation of the annotators’ characteristics and true segmentation label is achieved by encouraging the estimated annotators to be maximally unreliable while achieving high fidelity with the training data. Our method can also be viewed as a translation of STAPLE, an established label aggregation framework proposed in Warfield et al. [1] to the supervised learning paradigm. We demonstrate first on a generic segmentation task using MNIST data and then adapt for usage with MRI scans of multiple sclerosis (MS) patients for lesion labelling. Our method shows considerable improvement over the relevant baselines on both datasets in terms of segmentation accuracy and estimation of annotator reliability, particularly when only a single label is available per image. An open-source implementation of our approach can be found at https://github.com/UCLBrain/MSLS

    Fake supersymmetry versus Hamilton-Jacobi

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    We explain when the first-order Hamilton-Jacobi equations for black holes (and domain walls) in (gauged) supergravity, reduce to the usual first-order equations derived from a fake superpotential. This turns out to be equivalent to the vanishing of a newly found constant of motion and we illustrate this with various examples. We show that fake supersymmetry is a necessary condition for having physically sensible extremal black hole solutions. We furthermore observe that small black holes become scaling solutions near the horizon. When combined with fake supersymmetry, this leads to a precise extension of the attractor mechanism to small black holes: The attractor solution is such that the scalars move on specific curves, determined by the black hole charges, that are purely geodesic, although there is a non-zero potential.Comment: 20 pages, v2: Typos corrected, references adde

    Kerr-AdS and its Near-horizon Geometry: Perturbations and the Kerr/CFT Correspondence

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    We investigate linear perturbations of spin-s fields in the Kerr-AdS black hole and in its near-horizon geometry (NHEK-AdS), using the Teukolsky master equation and the Hertz potential. In the NHEK-AdS geometry we solve the associated angular equation numerically and the radial equation exactly. Having these explicit solutions at hand, we search for linear mode instabilities. We do not find any (non-)axisymmetric instabilities with outgoing boundary conditions. This is in agreement with a recent conjecture relating the linearized stability properties of the full geometry with those of its near-horizon geometry. Moreover, we find that the asymptotic behaviour of the metric perturbations in NHEK-AdS violates the fall-off conditions imposed in the formulation of the Kerr/CFT correspondence (the only exception being the axisymmetric sector of perturbations).Comment: 26 pages. 4 figures. v2: references added. matches published versio

    A non-linear VAD for noisy environments

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    This paper deals with non-linear transformations for improving the performance of an entropy-based voice activity detector (VAD). The idea to use a non-linear transformation has already been applied in the field of speech linear prediction, or linear predictive coding (LPC), based on source separation techniques, where a score function is added to classical equations in order to take into account the true distribution of the signal. We explore the possibility of estimating the entropy of frames after calculating its score function, instead of using original frames. We observe that if the signal is clean, the estimated entropy is essentially the same; if the signal is noisy, however, the frames transformed using the score function may give entropy that is different in voiced frames as compared to nonvoiced ones. Experimental evidence is given to show that this fact enables voice activity detection under high noise, where the simple entropy method fails

    Holography at an Extremal De Sitter Horizon

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    Rotating maximal black holes in four-dimensional de Sitter space, for which the outer event horizon coincides with the cosmological horizon, have an infinite near-horizon region described by the rotating Nariai metric. We show that the asymptotic symmetry group at the spacelike future boundary of the near-horizon region contains a Virasoro algebra with a real, positive central charge. This is evidence that quantum gravity in a rotating Nariai background is dual to a two-dimensional Euclidean conformal field theory. These results are related to the Kerr/CFT correspondence for extremal black holes, but have two key differences: one of the black hole event horizons has been traded for the cosmological horizon, and the near-horizon geometry is a fiber over dS_2 rather than AdS_2.Comment: 15 page

    Germline heterozygous DDX41 variants in a subset of familial myelodysplasia and acute myeloid leukemia

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    The Brazilian National Council for Scientific and Technological Development), Bloodwise, Children with Cancer and MRC (Medical Research Council, UK)
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