Non-linear adaptive control inspired by neuromuscular systems

Current paradigms for neuromorphic computing focus on internal computing mechanisms, for instance using spiking-neuron models. In this study, we propose to exploit what is known about neuro-mechanical control, exploiting the mechanisms of neural ensembles and recruitment, combined with the use of second-order overdamped impulse responses corresponding to the mechanical twitches of muscle-fiber groups. Such systems may be used for controlling any analog process, by realizing three aspects: Timing, output quantity representation and wave-shape approximation. We present an electronic based model implementing a single motor unit for twitch generation. Such units can be used to construct random ensembles, separately for an agonist and antagonist 'muscle'. Adaptivity is realized by assuming a multi-state memristive system for determining time constants in the circuit. Using (Spice)-based simulations, several control tasks were implemented which involved timing, amplitude and wave shape: The inverted pendulum task, the 'whack-a-mole' task and a handwriting simulation. The proposed model can be used for both electric-to-electronic as well as electric-to-mechanical tasks. In particular, the ensemble-based approach and local adaptivity may be of use in future multi-fiber polymer or multi-actuator pneumatic artificial muscles, allowing for robust control under varying conditions and fatigue, as is the case in biological muscles

ADAMTS-1 and syndecan 4 intersect in the regulation of cell migration and angiogenesis

The extracellular proteoglycanase ADAMTS-1 has critical roles in organogenesis and angiogenesis. We demonstrate here the functional convergence of ADAMTS-1 and the transmembrane heparan sulfate proteoglycan syndecan 4 in influencing adhesion, migration, and angiogenesis in vitro. Knockdown of ADAMTS-1 resulted in a parallel reduction in cell surface syndecan 4 that was not due to altered syndecan4 expression or internalisation, but was attributable to increased expression and activity of matrix metalloproteinase 9 (MMP-9), a known syndecan 4 sheddase. Knockdown of either syndecan 4 or ADAMTS-1 led to enhanced endothelial cell responses to exogenous vascular endothelial growth factor (VEGF), and increased microvessel sprouting in ex vivo aortic ring assays, correlating with reduced ability of the cells to sequester VEGF. On fibronectin, but not type 1 collagen matrices, knockdown of either ADAMTS-1 or syndecan 4 elicited increased migration and altered focal adhesion morphologies, with a higher proportion of larger focal adhesions and formation of long fibrillar integrin α5-containing focal adhesions. Integrin α5-null endothelial cells also displayed enhanced migration in response to ADAMTS-1/syndecan 4 knockdown, indicating that integrin α5 was not the mediator of the altered migratory behaviour. Plating of naïve endothelial cells on cellconditioned matrix from ADAMTS-1/syndecan 4 knockdown cells demonstrated that the altered behaviour was matrix dependent. Fibulin-1, a known ECM co-factor of ADAMTS-1, was expressed at reduced levels in ADAMTS-1/syndecan 4 knockdown cells. These findings support the notion that ADAMTS-1 and syndecan 4 are functionally interconnected in regulating cell migration and angiogenesis, via the involvement of MMP-9 and fibulin-1 as collaborators

ADAMTS-1 and Syndecan-4 intersect in the regulation of cell migration and angiogenesis

ADAMTS-1 is an extracellular protease with critical roles in organogenesis and angiogenesis. Here we demonstrate a functional convergence of ADAMTS-1 and the transmembrane heparan sulfate proteoglycan syndecan-4 in influencing adhesion, migration and angiogenesis. Knockdown of ADAMTS-1 in endothelial cells resulted in a parallel reduction in cell surface syndecan-4, attributable to increased matrix metalloproteinase-9 (MMP9) activity. Knockdown of either ADAMTS-1 or syndecan-4 increased cellular responses to vascular endothelial growth factor A isoform VEGFA164, and increased ex vivo aortic ring microvessel sprouting. On fibronectin, knockdown of either protein enhanced migration and promoted formation of long α5 integrin-containing fibrillar adhesions. However, integrin α5 null cells still showed increased migration in response to ADAMTS-1 and syndecan-4 siRNA treatment. Plating of naïve endothelial cells on cell-conditioned matrix from ADAMTS-1 and syndecan-4 knockdown cells demonstrated that the altered adhesive behaviour was matrix dependent, and this correlated with a lack of expression of fibulin-1: an extracellular matrix co-factor for ADAMTS-1 that is known to inhibit migration. These findings support the notion that ADAMTS-1 and syndecan-4 are functionally interconnected in regulating cell migration and angiogenesis, via collaboration with MMP9 and fibulin-1.This article has an associated First Person interview with the first author of the paper

NRP2 as an Emerging Angiogenic Player; Promoting Endothelial Cell Adhesion and Migration by Regulating Recycling of α5 Integrin.

Angiogenesis relies on the ability of endothelial cells (ECs) to migrate over the extracellular matrix via integrin receptors to respond to an angiogenic stimulus. Of the two neuropilin (NRP) orthologs to be identified, both have been reported to be expressed on normal blood and lymphatic ECs, and to play roles in the formation of blood and lymphatic vascular networks during angiogenesis. Whilst the role of NRP1 and its interactions with integrins during angiogenesis has been widely studied, the role of NRP2 in ECs is poorly understood. Here we demonstrate that NRP2 promotes Rac-1 mediated EC adhesion and migration over fibronectin (FN) matrices in a mechanistically distinct fashion to NRP1, showing no dependence on β3 integrin (ITGB3) expression, or VEGF stimulation. Furthermore, we highlight evidence of a regulatory crosstalk between NRP2 and α5 integrin (ITGA5) in ECs, with NRP2 depletion eliciting an upregulation of ITGA5 expression and disruptions in ITGA5 cellular organization. Finally, we propose a mechanism whereby NRP2 promotes ITGA5 recycling in ECs; NRP2 depleted ECs were found to exhibit reduced levels of total ITGA5 subunit recycling compared to wild-type (WT) ECs. Our findings expose NRP2 as a novel angiogenic player by promoting ITGA5-mediated EC adhesion and migration on FN

The Australian Space Eye: studying the history of galaxy formation with a CubeSat

The Australian Space Eye is a proposed astronomical telescope based on a 6U CubeSat platform. The Space Eye will exploit the low level of systematic errors achievable with a small space based telescope to enable high accuracy measurements of the optical extragalactic background light and low surface brightness emission around nearby galaxies. This project is also a demonstrator for several technologies with general applicability to astronomical observations from nanosatellites. Space Eye is based around a 90 mm aperture clear aperture all refractive telescope for broadband wide field imaging in the i and z bands.Comment: 19 pages, 14 figures, submitted for publication as Proc. SPIE 9904, 9904-56 (SPIE Astronomical Telescopes & Instrumentation 2016

Impact of availability of guidelines and active surveillance in reducing the incidence of ventilator-associated pneumonia in Europe and worldwide

Background: To analyse whether the availability of written standards for management of mechanically ventilated patients and/or the existence of a surveillance system for cases of ventilation-associated pneumonia (VAP) are positively associated with compliance with 6 well-established VAP prevention measures. Methods: Ecological study based on responses to an online-questionnaire completed by 1730 critical care physicians. Replies were received from 77 different countries, of which the majority, i.e. 1351, came from 36 European countries. Results: On a cross-country level, compliance with VAP prevention measures is higher in countries with a large number of prevention standards and/or VAP surveillance systems in place at ICU level., Likewise, implementation of standards and VAP surveillance systems has a significant impact on self-reported total compliance with VAP prevention measures (both p < 0.001). Moreover, predictions of overall prevention measure compliance show the effect size of the availability of written standards and existence of surveillance system. For instance, a female physician with 10 years of experience in critical care working in a 15-bed ICU in France has a predicted baseline level of VAP prevention measure compliance of 63 per cent. This baseline level increases by 9.5 percentage points (p < 0.001) if a written clinical VAP prevention standard is available in the ICU, and by another 4 percentage points (p < 0.001) if complemented by a VAP surveillance system. Conclusions: The existence of written standards for management of mechanically ventilated patients in an ICU and the availability of VAP surveillance systems have shown to be positively associated with compliance with VAP prevention measures and should be fostered on a policy level

Efficacy and safety of intermittent intravenous outpatient administration of levosimendan in patients with advanced heart failure: the LION-HEART multicentre randomised trial

Aims. The LION‐HEART study was a multicentre, double‐blind, randomised, parallel‐group, placebo‐controlled trial evaluating the efficacy and safety of intravenous administration of intermittent doses of levosimendan in outpatients with advanced chronic heart failure. Methods and results. Sixty‐nine patients from 12 centres were randomly assigned at a 2:1 ratio to levosimendan or placebo groups, receiving treatment by a 6‐hour intravenous infusion (0.2 μg/kg/min without bolus) every 2 weeks for 12 weeks. The primary endpoint was the effect on serum concentrations of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) throughout the treatment period in comparison with placebo. Secondary endpoints included evaluation of safety, clinical events and health‐related quality of life (HRQoL). The area under the curve (AUC, pg.day/mL) of the levels of NT‐proBNP over time for patients who received levosimendan was significantly lower than for the placebo group (344 × 103 [95% Confidence Interval (CI) 283 × 103−404 × 103] vs. 535 × 103 [443 × 103−626 × 103], p = 0.003). In comparison with the placebo group, the patients on levosimendan experienced a reduction in the rate of heart failure hospitalisation (hazard ratio 0.25; 95% CI 0.11-0.56; P = 0.001). Patients on levosimendan were less likely to experience a clinically significant decline in HRQoL over time (P = 0.022). Adverse event rates were similar in the two treatment groups. Conclusions. In this small pilot study, intermittent administration of levosimendan to ambulatory patients with advanced systolic heart failure reduced plasma concentrations of NT‐proBNP, worsening of HRQoL and hospitalisation for heart failure. The efficacy and safety of this intervention should be confirmed in larger trials

Fast Fitting of the Dynamic Memdiode Model to the Conduction Characteristics of RRAM Devices Using Convolutional Neural Networks

In this paper, the use of Artificial Neural Networks (ANNs) in the form of Convolutional Neural Networks (AlexNET) for the fast and energy-efficient fitting of the Dynamic Memdiode Model (DMM) to the conduction characteristics of bipolar-type resistive switching (RS) devices is investigated. Despite an initial computationally intensive training phase the ANNs allow obtaining a mapping between the experimental Current-Voltage (I-V) curve and the corresponding DMM parameters without incurring a costly iterative process as typically considered in error minimization-based optimization algorithms. In order to demonstrate the fitting capabilities of the proposed approach, a complete set of I-Vs obtained from Y₂O₃-based RRAM devices, fabricated with different oxidation conditions and measured with different current compliances, is considered. In this way, in addition to the intrinsic RS variability, extrinsic variation is achieved by means of external factors (oxygen content and damage control during the set process). We show that the reported method provides a significant reduction of the fitting time (one order of magnitude), especially in the case of large data sets. This issue is crucial when the extraction of the model parameters and their statistical characterization are required

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy