55 research outputs found
Demonstrating Advantages of Neuromorphic Computation: A Pilot Study
Neuromorphic devices represent an attempt to mimic aspects of the brain's
architecture and dynamics with the aim of replicating its hallmark functional
capabilities in terms of computational power, robust learning and energy
efficiency. We employ a single-chip prototype of the BrainScaleS 2 neuromorphic
system to implement a proof-of-concept demonstration of reward-modulated
spike-timing-dependent plasticity in a spiking network that learns to play the
Pong video game by smooth pursuit. This system combines an electronic
mixed-signal substrate for emulating neuron and synapse dynamics with an
embedded digital processor for on-chip learning, which in this work also serves
to simulate the virtual environment and learning agent. The analog emulation of
neuronal membrane dynamics enables a 1000-fold acceleration with respect to
biological real-time, with the entire chip operating on a power budget of 57mW.
Compared to an equivalent simulation using state-of-the-art software, the
on-chip emulation is at least one order of magnitude faster and three orders of
magnitude more energy-efficient. We demonstrate how on-chip learning can
mitigate the effects of fixed-pattern noise, which is unavoidable in analog
substrates, while making use of temporal variability for action exploration.
Learning compensates imperfections of the physical substrate, as manifested in
neuronal parameter variability, by adapting synaptic weights to match
respective excitability of individual neurons.Comment: Added measurements with noise in NEST simulation, add notice about
journal publication. Frontiers in Neuromorphic Engineering (2019
Versatile emulation of spiking neural networks on an accelerated neuromorphic substrate
We present first experimental results on the novel BrainScaleS-2 neuromorphic
architecture based on an analog neuro-synaptic core and augmented by embedded
microprocessors for complex plasticity and experiment control. The high
acceleration factor of 1000 compared to biological dynamics enables the
execution of computationally expensive tasks, by allowing the fast emulation of
long-duration experiments or rapid iteration over many consecutive trials. The
flexibility of our architecture is demonstrated in a suite of five distinct
experiments, which emphasize different aspects of the BrainScaleS-2 system
Influence of the Stability of a Fused Protein and Its Distance to the Amyloidogenic Segment on Fibril Formation
Conversion of native proteins into amyloid fibrils is irreversible and therefore it is difficult to study the interdependence of conformational stability and fibrillation by thermodynamic analyses. Here we approached this problem by fusing amyloidogenic poly-alanine segments derived from the N-terminal domain of the nuclear poly (A) binding protein PABPN1 with a well studied, reversibly unfolding protein, CspB from Bacillus subtilis. Earlier studies had indicated that CspB could maintain its folded structure in fibrils, when it was separated from the amyloidogenic segment by a long linker. When CspB is directly fused with the amyloidogenic segment, it unfolds because its N-terminal chain region becomes integrated into the fibrillar core, as shown by protease mapping experiments. Spacers of either 3 or 16 residues between CspB and the amyloidogenic segment were not sufficient to prevent this loss of CspB structure. Since the low thermodynamic stability of CspB (ΔGD = 12.4 kJ/mol) might be responsible for unfolding and integration of CspB into fibrils, fusions with a CspB mutant with enhanced thermodynamic stability (ΔGD = 26.9 kJ/mol) were studied. This strongly stabilized CspB remained folded and prevented fibril formation in all fusions. Our data show that the conformational stability of a linked, independently structured protein domain can control fibril formation
Synthesis of a new HYNIC-DAPI derivative for labelling with ⁹⁹ᵐTechnetium and its in vitro evaluation in an FRTL5 cell line
4′,6-Diamidine-2-phenylindole (DAPI) is a common fluorochrome that is able to bind to deoxyribonucleic acid (DNA) with distinct, sequence-dependent enhancement of fluorescence. This work presents the synthesis of a new multifunctional compound that includes the fluorescent dye as a ⁹⁹ᵐTechnetium (⁹⁹ᵐTc) carrier. A new technique for the bioconjugation of DAPI with 6-hydrazinonicotinic acid (HYNIC) through an amide linkage was developed. The radiolabelling was performed with HYNIC as a chelator and N-IJ2-hydroxy-1,1-bisIJhydroxymethyl)ethyl)glycine (tricine) as a coligand. Furthermore, experimental evidence showed that ⁹⁹ᵐTc complexes with DAPI as DNA-binding moieties are detectable in living Fischer rat thyroid follicular cell line 5 (FRTL5) and their nuclei. The investigations indicated further that the new HYNIC-DAPI derivative is able to interact with double-stranded DNA. This establishes the possibility of locating ⁹⁹ᵐTc in close proximity to biological structures of living cells, of which especially the genetic information-carrying cell compartments are at the centre of interest. In this context, further investigations are related to the radiotoxic effects of DNA-bound ⁹⁹ᵐTc-HYNIC-DAPI derivatives and dosimetric calculations
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