Adaptive motor control and learning in a spiking neural network realised on a mixed-signal neuromorphic processor

Neuromorphic computing is a new paradigm for design of both the computing hardware and algorithms inspired by biological neural networks. The event-based nature and the inherent parallelism make neuromorphic computing a promising paradigm for building efficient neural network based architectures for control of fast and agile robots. In this paper, we present a spiking neural network architecture that uses sensory feedback to control rotational velocity of a robotic vehicle. When the velocity reaches the target value, the mapping from the target velocity of the vehicle to the correct motor command, both represented in the spiking neural network on the neuromorphic device, is autonomously stored on the device using on-chip plastic synaptic weights. We validate the controller using a wheel motor of a miniature mobile vehicle and inertia measurement unit as the sensory feedback and demonstrate online learning of a simple 'inverse model' in a two-layer spiking neural network on the neuromorphic chip. The prototype neuromorphic device that features 256 spiking neurons allows us to realise a simple proof of concept architecture for the purely neuromorphic motor control and learning. The architecture can be easily scaled-up if a larger neuromorphic device is available.Comment: 6+1 pages, 4 figures, will appear in one of the Robotics conference

Land-use experiments in the Loch Laidon Catchment. Eighth report on Stream Water Quality to the Rannoch Trust

This report presents the results from the Stream Water Quality component of the Loch Laidon catchment land-use experiment which began in 1992. The experiment was set up to examine the effects of cattle grazing on the aquatic and terrestrial habitats and biota of a moorland area of upland Scotland

Land-use experiments in the Loch Laidon Catchment: 2007 data report on Stream Water Quality to the Rannoch Trust

In 1992 the Rannoch Trust established the Loch Laidon catchment land-use experiment, which is investigating the effects of summer cattle grazing on the terrestrial and aquatic upland environment. Situated in Perthshire, Scotland, the study area falls within a number of designations, including the Rannoch Moor Special Area of Conservation and Site of Special Scientific Interest, the Rannoch Lochs Special Protection Area and the Tayside Local Biodiversity Action Plan

Land-use experiments in the Loch Laidon catchment: sixth report on stream water quality to the Rannoch Trust

This report presents and summarises data from the Stream Water Quality project instigated by the Rannoch Trust in 1992. The project is a component of the Loch Laidon Catchment land-use experiment, which is investigating the effects of differing cattle grazing regimes on the terrestrial and aquatic upland environment. Allott et al (1994) described the project rationale and background whilst progress reports (see References) have provided ongoing updates of the accumulating dataset

Therapeutic Strategies to Reduce the Toxicity of Misfolded Protein Oligomers.

The aberrant aggregation of proteins is implicated in the onset and pathogenesis of a wide range of neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Mounting evidence indicates that misfolded protein oligomers produced as intermediates in the aggregation process are potent neurotoxic agents in these diseases. Because of the transient and heterogeneous nature of these elusive aggregates, however, it has proven challenging to develop therapeutics that can effectively target them. Here, we review approaches aimed at reducing oligomer toxicity, including (1) modulating the oligomer populations (e.g., by altering the kinetics of aggregation by inhibiting, enhancing, or redirecting the process), (2) modulating the oligomer properties (e.g., through the size-hydrophobicity-toxicity relationship), (3) modulating the oligomer interactions (e.g., by protecting cell membranes by displacing oligomers), and (4) reducing oligomer toxicity by potentiating the protein homeostasis system. We analyze examples of these complementary approaches, which may lead to the development of compounds capable of preventing or treating neurodegenerative disorders associated with protein aggregation

Squalamine and Its Derivatives Modulate the Aggregation of Amyloid-β and α-Synuclein and Suppress the Toxicity of Their Oligomers.

The aberrant aggregation of proteins is a key molecular event in the development and progression of a wide range of neurodegenerative disorders. We have shown previously that squalamine and trodusquemine, two natural products in the aminosterol class, can modulate the aggregation of the amyloid-β peptide (Aβ) and of α-synuclein (αS), which are associated with Alzheimer's and Parkinson's diseases. In this work, we expand our previous analyses to two squalamine derivatives, des-squalamine and α-squalamine, obtaining further insights into the mechanism by which aminosterols modulate Aβ and αS aggregation. We then characterize the ability of these small molecules to alter the physicochemical properties of stabilized oligomeric species in vitro and to suppress the toxicity of these aggregates to varying degrees toward human neuroblastoma cells. We found that, despite the fact that these aminosterols exert opposing effects on Aβ and αS aggregation under the conditions that we tested, the modifications that they induced to the toxicity of oligomers were similar. Our results indicate that the suppression of toxicity is mediated by the displacement of toxic oligomeric species from cellular membranes by the aminosterols. This study, thus, provides evidence that aminosterols could be rationally optimized in drug discovery programs to target oligomer toxicity in Alzheimer's and Parkinson's diseases

Entrepreneurial orientation and the business performance of SMEs: a quantitative study from the Netherlands

Entrepreneurial Orientation (EO) is often mentioned as an antecedent of growth, competitive advantage and superior performance, and prior empirical research has often shown a positive relationship between EO and performance appears to exist. However, an important question that remains unanswered is what effect EO might have on firm performance during periods of economic crisis, and the severe environmental turbulence that accompany such crises. This research is a first investigation towards the effects of EO on the performance of small and medium sized firms during the current global economic crisis. In this study we use the multidimensional model of EO and test a series of hypotheses pertaining to its performance effects using survey data gathered from 164 Dutch SMEs. The present research shows that proactive firm behavior positively contributes to SME performance during the economic crisis. We further show that innovative SMEs do perform better in turbulent environments, but those innovative SMEs should minimize the level of risk and should take action to avoid projects that are too risky

Rationally Designed Antibodies as Research Tools to Study the Structure–Toxicity Relationship of Amyloid-β Oligomers

Alzheimer’s disease is associated with the aggregation of the amyloid-β peptide (Aβ), resulting in the deposition of amyloid plaques in brain tissue. Recent scrutiny of the mechanisms by which Aβ aggregates induce neuronal dysfunction has highlighted the importance of the Aβ oligomers of this protein fragment. Because of the transient and heterogeneous nature of these oligomers, however, it has been challenging to investigate the detailed mechanisms by which these species exert cytotoxicity. To address this problem, we demonstrate here the use of rationally designed single-domain antibodies (DesAbs) to characterize the structure−toxicity relationship of Aβ oligomers. For this purpose, we use Zn2+-stabilized oligomers of the 40-residue form of Aβ (Aβ40) as models of brain Aβ oligomers and two single-domain antibodies (DesAb18-24 and DesAb34-40), designed to bind to epitopes at residues 18−24 and 34−40 of Aβ40, respectively. We found that the DesAbs induce a change in structure of the Zn2+-stabilized Aβ40 oligomers, generating a simultaneous increase in their size and solvent-exposed hydrophobicity. We then observed that these increments in both the size and hydrophobicity of the oligomers neutralize each other in terms of their effects on cytotoxicity, as predicted by a recently proposed general structure−toxicity relationship, and observed experimentally. These results illustrate the use of the DesAbs as research tools to investigate the biophysical and cytotoxicity properties of Aβ oligomers