8,573 research outputs found
Memristive excitable cellular automata
The memristor is a device whose resistance changes depending on the polarity
and magnitude of a voltage applied to the device's terminals. We design a
minimalistic model of a regular network of memristors using
structurally-dynamic cellular automata. Each cell gets info about states of its
closest neighbours via incoming links. A link can be one 'conductive' or
'non-conductive' states. States of every link are updated depending on states
of cells the link connects. Every cell of a memristive automaton takes three
states: resting, excited (analog of positive polarity) and refractory (analog
of negative polarity). A cell updates its state depending on states of its
closest neighbours which are connected to the cell via 'conductive' links. We
study behaviour of memristive automata in response to point-wise and spatially
extended perturbations, structure of localised excitations coupled with
topological defects, interfacial mobile excitations and growth of information
pathways.Comment: Accepted to Int J Bifurcation and Chaos (2011
Characterizing Molecular Modifiers of Pathogenesis in Spinobulbar Muscular Atrophy.
Spinobulbar muscular atrophy (SBMA), or Kennedy’s disease, is an inherited neuromuscular disorder caused by a polyglutamine (polyQ) tract expansion in the androgen receptor (AR). This mutation initiates misfolding and aggregation of AR, eliciting toxicity in motor neurons, progressive weakness, and muscle atrophy. PolyQ expansion also compromises the transactivation function of AR in response to androgens, resulting in androgen insensitivity. Although considerable progress has been made in characterizing molecular consequences of the polyQ mutation in SBMA, many aspects of pathogenesis, and in particular the cellular processes that modify disease development, remain incompletely understood.
Based on previous work suggesting a pathogenic role of autophagy in SBMA, I use cellular and mouse models to delineate the state of autophagy in SBMA. I show that autophagy is induced in SBMA cells and diseased tissues, and that this is due to depressed mTOR activity. These changes correlate with activity of the transcription factors TFEB and ZKSCAN3, which coordinate expression of autophagy-related genes in SBMA mice and human patients. Furthermore, these alterations in autophagy regulators lead to enhanced responsiveness to stimulation by nutrient deprivation and exercise. These results indicate that dysregulated transcriptional programming promotes induction of autophagy in SBMA and provide evidence for targeting autophagy for therapeutic inhibition.
Given the previously established role of small ubiquitin-like modifier (SUMO) on AR function, I characterize a novel knock-in mouse model of SBMA to address the influence of SUMO on SBMA pathogenesis. We introduce mutations that prevent SUMOylation of polyQ AR (AR113Q-KRKR) and demonstrate that, despite unaltered androgen insensitivity and neuromuscular pathology, AR113Q-KRKR mice display a striking extension of lifespan and recovery of exercise tolerance. Complementary expression analysis of the non-SUMOylatable polyQ AR reveals substantial expansion of the receptor’s transactivation activity. These findings suggest that abrogating SUMO modification of polyQ AR mediates amelioration of the SBMA phenotype, in part by improving skeletal muscle physiology. Additionally, these studies not only reveal new insights in the comparative roles of polyQ AR toxicity versus loss of function in affected tissues, but they also establish the benefits of enhancing AR function in SBMA for therapeutic design.PHDNeuroscienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111409/1/jaschua_1.pd
Composition ot Glvceride Esters of Lauric Acid bV FTIR Band Shape Analysis
Synthesis of glyceride esters of a fatty acid produces a mixture of isomers that are difficult to separate and analyze, requiring high temperature GC in most cases particularly for long-chain esters. In this paper, we present a fast estimation of the composition of the glyceride esters of lauric acid and glycerol (monolaurin, dilaurin, and trilaurin) by FTIR band shape analysis. The method uses the fact that the carbonyl stretching regions of the pure glycerides have differentband shapes, which implies any composite band of a mixture of glycerides may be resolved into the component peaks due to each glyceride. The carbonyl band region was fitted with five component peaks using a commercial peak-fitting program. The peak at 1745 cm-1 is characteristic of trilaurin whereas the peaks at 1740 cm-1 and 1731 cm-1 provide a unique height ratio for mono- and dilaurin. Calibration curves were prepared and a system of two equations may be solved to obtain the composition of mono-, di-, and trilaurin. This method was tested with known mixtures of the glycerides yielding estimates within ± 10 % composition units
Tele-operated high speed anthropomorphic dextrous hands with object shape and texture identification
This paper reports on the development of two number of robotic hands have been developed which focus on tele-operated high speed anthropomorphic dextrous robotic hands. The aim of developing these hands was to achieve a system that seamlessly interfaced between humans and robots. To provide sensory feedback, to a remote operator tactile sensors were developed to be mounted on the robotic hands. Two systems were developed, the first, being a skin sensor capable of shape reconstruction placed on the palm of the hand to feed back the shape of objects grasped and the second is a highly sensitive tactile array for surface texture identification
Control of Multi-level Voltage States in a Hysteretic SQUID Ring-Resonator System
In this paper we study numerical solutions to the quasi-classical equations
of motion for a SQUID ring-radio frequency (rf) resonator system in the regime
where the ring is highly hysteretic. In line with experiment, we show that for
a suitable choice of of ring circuit parameters the solutions to these
equations of motion comprise sets of levels in the rf voltage-current dynamics
of the coupled system. We further demonstrate that transitions, both up and
down, between these levels can be controlled by voltage pulses applied to the
system, thus opening up the possibility of high order (e.g. 10 state),
multi-level logic and memory.Comment: 8 pages, 9 figure
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Binding to medium and long chain fatty acyls is a common property of HEAT and ARM repeat modules.
Covalent post-translational modification (PTM) of proteins with acyl groups of various carbon chain-lengths regulates diverse biological processes ranging from chromatin dynamics to subcellular localization. While the YEATS domain has been found to be a prominent reader of acetylation and other short acyl modifications, whether additional acyl-lysine reader domains exist, particularly for longer carbon chains, is unclear. Here, we employed a quantitative proteomic approach using various modified peptide baits to identify reader proteins of various acyl modifications. We discovered that proteins harboring HEAT and ARM repeats bind to lysine myristoylated peptides. Recombinant HEAT and ARM repeats bind to myristoylated peptides independent of the peptide sequence or the position of the myristoyl group. Indeed, HEAT and ARM repeats bind directly to medium- and long-chain free fatty acids (MCFA and LCFA). Lipidomic experiments suggest that MCFAs and LCFAs interact with HEAT and ARM repeat proteins in mammalian cells. Finally, treatment of cells with exogenous MCFAs and inhibitors of MCFA-CoA synthases increase the transactivation activity of the ARM repeat protein β-catenin. Taken together, our results suggest an unappreciated role for fatty acids in the regulation of proteins harboring HEAT or ARM repeats
Sampling rare fluctuations of height in the Oslo ricepile model
We have studied large deviations of the height of the pile from its mean
value in the Oslo ricepile model. We sampled these very rare events with
probabilities of order by Monte Carlo simulations using importance
sampling. These simulations check our qualitative arguement [Phys. Rev. E, {\bf
73}, 021303, 2006] that in steady state of the Oslo ricepile model, the
probability of large negative height fluctuations about
the mean varies as as with
held fixed, and .Comment: 7 pages, 8 figure
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