Regional myocardial blood flow, function and metabolism using phosphorus-31 nuclear magnetic resonance spectroscopy during ischemia and reperfusion in dogs

Postreperfusion regional myocardial dysfunction may be associated with depletion of high energy phosphate compounds during ischemia and with their relatively slow repletion during reperfusion. However, few studies have correlated relatively rapid changes in regional myocardial function (sonomicrometers) and blood flow (microspheres) with high energy phosphate concentrations measured using phosphorus-31 nuclear magnetic resonance spectroscopy in intact large animal models of regional myocardial ischemia. The left anterior descending coronary artery of mongrel dogs was abruptly occluded for 17.1 ± 1.9 minutes and then completely released; measurements were made for an additional 22 minutes. Transmural blood flow decreased from 1.07 ± 0.25 to 0.25 ± 0.10 ml/(min × g) and holosystolic expansion was observed in all dogs (segmental systolic shortening decreased from 9.3 ± 3.7 to −6.3 ± 6.0%). Phosphocreatine (PCr) measured during 4.4 minute sampling intervals decreased to steady state within the first sampling period after occlusion and was 45.9 ± 17.0% of control at the end of the occlusion, whereas beta-adenosine triphosphate (beta-ATP) reached its lowest level early after reperfusion (72.7 ± 13.3% of control). The ratio of PCr to inorganic phosphate (Pi) decreased during the occlusion (3.34 ± 0.75 versus 1.01 ± 0.61) but returned to control level early during reperfusion. The ratio of PCr to beta-ATP also decreased during coronary occlusion (2.16 ± 0.39 versus 1.29 ± 0.39) but did not return to control level during reperfusion.Significant correlations were observed between the intensity of ischemia (reduced blood flow) and reductions in regional contractile function, PCr, beta-ATP, myocardial pH and the increase in Pi during the coronary occlusion. Also during ischemia, there were significant correlations between regional contractile function and both myocardial pH and Pi. PCr returned to control level rapidly after reperfusion (95.9 ± 13.2% of control in less than 5 minutes of reperfusion) whereas beta-ATP recovered only partially after 22 minutes (80.0 ± 17.5% of control). The correlation between the fraction of control beta-ATP and the fraction of control regional function at this time was r = 0.84 (p = 0.017).These results demonstrate metabolic correlates to regional myocardial ischemia in an intact dog model using phosphorus-31 spectroscopy. Additionally during reperfusion, beta-ATP, but not PCr, could be associated with the recovery of regional segmental contractile function

Gait Generation and Optimization for Legged Robots

This paper presents a general framework for representing and generating gaitsfor legged robots. We introduce a convenient parametrization of gait generators as dynamical systems possessing specified stable limit cycles over an appropriate torus. Inspired by biology, this parametrization affords a continuous selection of operation within a coordination design plane spanned by axes that determine the mix of ”feedforward/feedback” and centralized/decentralized” control. Applying optimization to the parameterized gait generation system allowed RHex, our robotic hexapod, to learn new gaits demonstrating significant performance increases. For example, RHex can now run at 2.4m/s (up from 0.8m/s), run with a specific resistance of 0.6 (down from 2.0), climb 45◦ inclines (up from 25◦), and traverse 35◦ inclines (up from 15◦)

Impaired processing of facial happiness, with or without awareness, in developmental prosopagnosia

Developmental prosopagnosia (DP) is associated with severe, lifelong deficits in face recognition, with such cases often cited as support for a dissociation between the processing of facial identity and emotion. Here we examine the evidence against this dissociation and propose that the processing of facial happiness, either with or without awareness, is actually integrated within the same neural network involved in facial identity recognition. We also test this hypothesis on a group of DP cases and neurotypical controls (NT) by adapting them to expressionless neutral faces, intact happy faces and hybrid faces. Despite these hybrid faces being explicitly identified as expressionless due to their higher spatial frequencies taken from a neutral face, their low spatial frequencies convey happy facial expressions that participants are unaware of. After adaptation, participants were asked to judge the facial expressions of face stimuli that were morphed incrementally in varying degrees of sad through to happy. Both groups exhibited emotion adaptation aftereffects to the intact happy faces, although this effect was smaller in DP. Whereas NT produced emotion adaptation aftereffects without awareness of the happy emotion in the hybrid faces; as a group, those with DP did not. Furthermore, our DP cases also exhibited deficits in judging the emotion of the happiest morphed test faces. Our results indicate that the processing of happy facial expressions, with or without awareness, is likely integrated within the face recognition network. We hypothesise that the previously identified abnormalities in the fusiform gyrus in those with DP is the most likely structure responsible for these deficits.MOE (Min. of Education, S’pore)Accepted versio

Automated Gait Adaptation for Legged Robots

Gait parameter adaptation on a physical robot is an error-prone, tedious and time-consuming process. In this paper we present a system for gait adaptation in our RHex series of hexapedal robots that renders this arduous process nearly autonomous. The robot adapts its gait parameters by recourse to a modified version of Nelder-Mead descent while managing its self-experiments and measuring the outcome by visual servoing within a partially engineered environment. The resulting performance gains extend considerably beyond what we have managed with hand tuning. For example, the hest hand tuned alternating tripod gaits never exceeded 0.8 m/s nor achieved specific resistance helow 2.0. In contrast, Nelder-Mead based tuning has yielded alternating tripod gaits at 2.7 m/s (well over 5 body lengths per second) and reduced specific resistance to 0.6 while requiring little human intervention at low and moderate speeds. Comparable gains have been achieved on the much larger ruggedized version of this machine

Characterization of degeneration in the retina, brain and spinal cord of the Cln1 knockout mouse

Abstract only availableThe neuronal-ceroid lipofuscinoses (NCLs; often referred to as Battens Disease) are a group of hereditary disorders of childhood. Symptoms of NCLs are characterized by neurodegeneration with progressive neural cell death in the retina and central nervous system (CNS). The infantile form of NCL results from a deficiency in the protein, palmitoyl protein thioesterase-1 (PPT-1). PPT-1, encoded by the Cln1 gene, removes long chain fatty acids from modified cysteine residues in proteins. Mutations in the Cln1 gene are associated with an accumulation of autofluorescent lysosomal lipopigments in various tissues such as the retina and CNS. In the current study, we use a transgenic mouse model in which the gene for Cln1 has been mutated, i.e., 'knocked out'. Our goal is to perform histological experiments to assess the functional progression of neurodegenerative changes in the retina, brain and spinal cord as the subject ages. The retina, brain and spinal cord of the mice at different ages were fixed and embedded in plastic resin and/or paraffin. Thick sections (1 mm or 10 mm, respectively) were stained with toluidine blue or propidium iodide to detect neuronal loss and/or apoptosis as a result of the PPT-1 deficiency. Fluorescent images of the stained sections were obtained to document changes in tissue structure and the extent of degeneration. These studies provide information that will aid future studies in which stem cell transplants will be made into the Cln1 knockout mouse model. Ultimately, this approach will determine whether combined gene and stem cell therapies can be applied to patients with Battens Disease.Molecular Biology Progra

An Efficient Paradigm for Genetic Epidemiology Cohort Creation

Development of novel methodologies to efficiently create large genetic epidemiology cohorts is needed. Here we describe a rapid, precise and cost-efficient method for collection of DNA from cases previously experiencing an osteoporotic fracture by identifying cases using and administrative health-care databases. Over the course of 14 months we collected DNA from 1,130 women experiencing an osteoporotic fracture, at a cost of $54 per sample. This cohort is among the larger DNA osteoporotic fracture collections in the world. The novel method described addresses a major unmet health care research need and is widely applicable to any disease that can be identified accurately through administrative data

Superconducting and normal-state properties of the noncentrosymmetric superconductor Re3Ta

The noncentrosymmetric superconductor, Re3Ta, has been characterized in detail with a combination of magnetization, heat capacity, and electrical resistivity measurements, as well as a microscopic investigation of the internal magnetic fields using muon spin spectroscopy (μSR). In low applied fields, we observe 100% flux expulsion at a temperature of Tc = 4.68 K, which is concomitant with a sudden decrease of the electrical resistivity to zero and a sharp discontinuity in the heat capacity, confirming bulk superconductivity in this material. We find that Re3Ta is a poor metal, with superconductivity occurring in the dirty limit, and in which the disorder in the structure dominates the physical properties. Zero-field μSR shows that the superconducting state preserves time-reversal symmetry, and transverse-field measurements of the superfluid density are well described by an isotropic s-wave model. A careful analysis of the internal field distribution reveals a high level of disorder in the vortex lattice. Furthermore, we have combined the experimental data and calculated the effective mass, carrier density, and electronic mean-free path in this material, and ultimately show that Re3Ta lies close to the unconventional region of the Uemura plot