Towards a neural hierarchy of time scales for motor control

Animals show remarkable rich motion skills which are still far from realizable with robots. Inspired by the neural circuits which generate rhythmic motion patterns in the spinal cord of all vertebrates, one main research direction points towards the use of central pattern generators in robots. On of the key advantages of this, is that the dimensionality of the control problem is reduced. In this work we investigate this further by introducing a multi-timescale control hierarchy with at its core a hierarchy of recurrent neural networks. By means of some robot experiments, we demonstrate that this hierarchy can embed any rhythmic motor signal by imitation learning. Furthermore, the proposed hierarchy allows the tracking of several high level motion properties (e.g.: amplitude and offset), which are usually observed at a slower rate than the generated motion. Although these experiments are preliminary, the results are promising and have the potential to open the door for rich motor skills and advanced control

Contrast-enhanced micro-CT imaging in murine carotid arteries : a new protocol for computing wall shear stress

Background: Wall shear stress (WSS) is involved in the pathophysiology of atherosclerosis. The correlation between WSS and atherosclerosis can be investigated over time using a WSS-manipulated atherosclerotic mouse model. To determine WSS in vivo, detailed 3D geometry of the vessel network is required. However, a protocol to reconstruct 3D murine vasculature using this animal model is lacking. In this project, we evaluated the adequacy of eXIA 160, a small animal contrast agent, for assessing murine vascular network on micro-CT. Also, a protocol was established for vessel geometry segmentation and WSS analysis. Methods: A tapering cast was placed around the right common carotid artery (RCCA) of ApoE(-/-) mice (n = 8). Contrast-enhanced micro-CT was performed using eXIA 160. An innovative local threshold-based segmentation procedure was implemented to reconstruct 3D geometry of the RCCA. The reconstructed RCCA was compared to the vessel geometry using a global threshold-based segmentation method. Computational fluid dynamics was applied to compute the velocity field and WSS distribution along the RCCA. Results: eXIA 160-enhanced micro-CT allowed clear visualization and assessment of the RCCA in all eight animals. No adverse biological effects were observed from the use of eXIA 160. Segmentation using local threshold values generated more accurate RCCA geometry than the global threshold-based approach. Mouse-specific velocity data and the RCCA geometry generated 3D WSS maps with high resolution, enabling quantitative analysis of WSS. In all animals, we observed low WSS upstream of the cast. Downstream of the cast, asymmetric WSS patterns were revealed with variation in size and location between animals. Conclusions: eXIA 160 provided good contrast to reconstruct 3D vessel geometry and determine WSS patterns in the RCCA of the atherosclerotic mouse model. We established a novel local threshold-based segmentation protocol for RCCA reconstruction and WSS computation. The observed differences between animals indicate the necessity to use mouse-specific data for WSS analysis. For our future work, our protocol makes it possible to study in vivo WSS longitudinally over a growing plaque

Augmenting muscle diacylglycerol and triacylglycerol content by blocking fatty acid oxidation does not impede insulin sensitivity

A low fat oxidative capacity has been linked to muscle diacylglycerol (DAG) accumulation and insulin resistance. Alternatively, a low fat oxidation rate may stimulate glucose oxidation, thereby enhancing glucose disposal. Here, we investigated whether an ethyl-2-[6-(4-chlorophenoxy)hexyl]-oxirane-2-carboxylate (etomoxir)-induced inhibition of fat oxidation leads to muscle fat storage and insulin resistance. An intervention in healthy male subjects was combined with studies in human primary myotubes. Furthermore, muscle DAG and triacylglycerol (TAG), mitochondrial function, and insulin signaling were examined in etomoxir-treated C57bl6 mice. In humans, etomoxir administration increased glucose oxidation at the expense of fat oxidation. This effect was accompanied by an increased abundance of GLUT4 at the sarcolemma and a lowering of plasma glucose levels, indicative of improved glucose homeostasis. In mice, etomoxir injections resulted in accumulation of muscle TAG and DAG, yet improved insulin-stimulated GLUT4 translocation. Also in human myotubes, insulin signaling was improved by etomoxir, in the presence of increased intramyocellular lipid accumulation. These insulin-sensitizing effects in mice and human myotubes were accompanied by increased phosphorylation of AMP-activated protein kinase (AMPK). Our results show that a reduction in fat oxidation leading to accumulation of muscle DAG does not necessarily lead to insulin resistance, as the reduction in fat oxidation may activate AMPK

Antibodies specific for hypervariable regions 3 to 5 of the feline immunodeficiency virus envelope glycoprotein are not solely responsible for vaccine-induced acceleration of challenge infection in cats

In a previous vaccination study in cats, the authors reported on accelerated feline immunodeficiency virus (FIV) replication upon challenge in animals vaccinated with a candidate envelope subunit vaccine. Plasma transfer studies as well as antibody profiles in vaccinated cats indicated a causative role for antibodies directed against the hypervariable regions HV3, HV4 and HV5 (HV3-5) of the envelope glycoprotein. The present study was designed to investigate further the contribution of antibodies in envelope vaccine-induced acceleration of FIV infection. To this end, regions HV3-5 of the envelope glycoprotein were deleted from the original vaccine, thus addressing the contributing role of antibodies directed against these hypervariable regions. Interestingly, this approach did not prevent acceleration of challenge infection. Analysis of the antibody responses in the respective groups suggested that removal of HV3-5 redirected the humoral immune response towards other regions of the envelope glycoprotein, indicating that these regions can also induce antibodies that accelerate virus replication

An Endothelial Storage Granule for Tissue-Type Plasminogen Activator

In previous studies we have shown that, after stimulation by a receptor ligand such as thrombin, tissue-type plasminogen activator (tPA) and von Willebrand factor (vWf) will be acutely released from human umbilical vein endothelial cells (HUVEC). However, the mechanisms involved in the secretion of these two proteins differ in some respects, suggesting that the two proteins may be stored in different secretory granules

Human Skeletal Muscle Mitochondrial Uncoupling Is Associated with Cold Induced Adaptive Thermogenesis

Background: Mild cold exposure and overfeeding are known to elevate energy expenditure in mammals, including humans. This process is called adaptive thermogenesis. In small animals, adaptive thermogenesis is mainly caused by mitochondrial uncoupling in brown adipose tissue and regulated via the sympathetic nervous system. In humans, skeletal muscle is a candidate tissue, known to account for a large part of the epinephrine-induced increase in energy expenditure. However, mitochondrial uncoupling in skeletal muscle has not extensively been studied in relation to adaptive thermogenesis in humans. Therefore we hypothesized that cold-induced adaptive thermogenesis in humans is accompanied by an increase in mitochondrial uncoupling in skeletal muscle. Methodology/Principal Findings: The metabolic response to mild cold exposure in 11 lean, male subjects was measured in a respiration chamber at baseline and mild cold exposure. Skeletal muscle mitochondrial uncoupling (state 4) was measured in muscle biopsies taken at the end of the respiration chamber stays. Mild cold exposure caused a significant increase in 24h energy expenditure of 2.8 % (0.32 MJ/day, range of 20.21 to 1.66 MJ/day, p,0.05). The individual increases in energy expenditure correlated to state 4 respiration (p,0.02, R 2 = 0.50). Conclusions/Significance: This study for the first time shows that in humans, skeletal muscle has the intrinsic capacity for cold induced adaptive thermogenesis via mitochondrial uncoupling under physiological conditions. This opens possibilitie

Can biological quantum networks solve NP-hard problems?

There is a widespread view that the human brain is so complex that it cannot be efficiently simulated by universal Turing machines. During the last decades the question has therefore been raised whether we need to consider quantum effects to explain the imagined cognitive power of a conscious mind. This paper presents a personal view of several fields of philosophy and computational neurobiology in an attempt to suggest a realistic picture of how the brain might work as a basis for perception, consciousness and cognition. The purpose is to be able to identify and evaluate instances where quantum effects might play a significant role in cognitive processes. Not surprisingly, the conclusion is that quantum-enhanced cognition and intelligence are very unlikely to be found in biological brains. Quantum effects may certainly influence the functionality of various components and signalling pathways at the molecular level in the brain network, like ion ports, synapses, sensors, and enzymes. This might evidently influence the functionality of some nodes and perhaps even the overall intelligence of the brain network, but hardly give it any dramatically enhanced functionality. So, the conclusion is that biological quantum networks can only approximately solve small instances of NP-hard problems. On the other hand, artificial intelligence and machine learning implemented in complex dynamical systems based on genuine quantum networks can certainly be expected to show enhanced performance and quantum advantage compared with classical networks. Nevertheless, even quantum networks can only be expected to efficiently solve NP-hard problems approximately. In the end it is a question of precision - Nature is approximate.Comment: 38 page