Finite element modeling and in vivo analysis of electrode configurations for selective stimulation of pudendal afferent fibers

<p>Abstract</p> <p>Background</p> <p>Intraurethral electrical stimulation (IES) of pudendal afferent nerve fibers can evoke both excitatory and inhibitory bladder reflexes in cats. These pudendovesical reflexes are a potential substrate for restoring bladder function in persons with spinal cord injury or other neurological disorders. However, the complex distribution of pudendal afferent fibers along the lower urinary tract presents a challenge when trying to determine the optimal geometry and position of IES electrodes for evoking these reflexes. This study aimed to determine the optimal intraurethral electrode configuration(s) and locations for selectively activating targeted pudendal afferents to aid future preclinical and clinical investigations.</p> <p>Methods</p> <p>A finite element model (FEM) of the male cat urethra and surrounding structures was generated to simulate IES with a variety of electrode configurations and locations. The activating functions (AFs) along pudendal afferent branches innervating the cat urethra were determined. Additionally, the thresholds for activation of pudendal afferent branches were measured in α-chloralose anesthetized cats.</p> <p>Results</p> <p>Maximum AFs evoked by intraurethral stimulation in the FEM and in vivo threshold intensities were dependent on stimulation location and electrode configuration.</p> <p>Conclusions</p> <p>A ring electrode configuration is ideal for IES. Stimulation near the urethral meatus or prostate can activate the pudendal afferent fibers at the lowest intensities, and allowed selective activation of the dorsal penile nerve or cranial sensory nerve, respectively. Electrode location was a more important factor than electrode configuration for determining stimulation threshold intensity and nerve selectivity.</p

Improved crush energy absorption in 3D woven composites by pick density modification

Although 3D woven composites have exceptional out-of-plane properties, there is a lack of understanding for these materials in crash application in automotive and aerospace industries. To encourage the use of 3D wovens in crashworthy automotive structures, knowledge must be gained so that designers can adjust the highly flexible weave parameters to create tailor-made performance materials. Here we show that fabric pick density causes large changes in progressive failure modes and associated energy absorption, particularly in the dynamic regime, where the quasi-static to dynamic energy absorption loss typical of composites is completely removed. Compression and flexure properties, which are known to be linked to crash performance in composites, are also investigated for these 3D woven layer-to-layer interlock carbon-epoxy composite structures. 3D fabric preforms are manufactured in three different pick densities: 4, 10 & 16 wefts/cm. With a constant warp density of 12 warps/cm from carbon fibres. Increasing the pick density improved specific energy absorption (SEA) even in relatively inefficient progressive failure modes like folding, which has not previously observed in composite materials. SEA values up to 104 J/g (quasi-static) and 93 J/g (dynamic) are recorded. This work shows that minor weft direction (transverse) weave changes can lead to sizeable improvements in warp direction (axial) energy absorption without fundamentally redesigning the weave architecture

Observation of Electron-Hole Puddles in Graphene Using a Scanning Single Electron Transistor

The electronic density of states of graphene is equivalent to that of relativistic electrons. In the absence of disorder or external doping the Fermi energy lies at the Dirac point where the density of states vanishes. Although transport measurements at high carrier densities indicate rather high mobilities, many questions pertaining to disorder remain unanswered. In particular, it has been argued theoretically, that when the average carrier density is zero, the inescapable presence of disorder will lead to electron and hole puddles with equal probability. In this work, we use a scanning single electron transistor to image the carrier density landscape of graphene in the vicinity of the neutrality point. Our results clearly show the electron-hole puddles expected theoretically. In addition, our measurement technique enables to determine locally the density of states in graphene. In contrast to previously studied massive two dimensional electron systems, the kinetic contribution to the density of states accounts quantitatively for the measured signal. Our results suggests that exchange and correlation effects are either weak or have canceling contributions.Comment: 13 pages, 5 figure

A bayesian meta-analysis of multiple treatment comparisons of systemic regimens for advanced pancreatic cancer

© 2014 Chan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: For advanced pancreatic cancer, many regimens have been compared with gemcitabine (G) as the standard arm in randomized controlled trials. Few regimens have been directly compared with each other in randomized controlled trials and the relative efficacy and safety among them remains unclear

Human disc cells in monolayer vs 3D culture: cell shape, division and matrix formation

BACKGROUND: The relationship between cell shape, proliferation, and extracellular matrix (ECM) production, important aspects of cell behavior, is examined in a little-studied cell type, the human annulus cell from the intervertebral disc, during monolayer vs three-dimensional (3D) culture. RESULTS: Three experimental studies showed that cells respond specifically to culture microenvironments by changes in cell shape, mitosis and ECM production: 1) Cell passages showed extensive immunohistochemical evidence of Type I and II collagens only in 3D culture. Chondroitin sulfate and keratan sulfate were abundant in both monolayer and 3D cultures. 2) Cells showed significantly greater proliferation in monolayer in the presence of platelet-derived growth factor compared to cells in 3D. 3) Cells on Matrigel™-coated monolayer substrates became rounded and formed nodular colonies, a finding absent during monolayer growth. CONCLUSIONS: The cell's in vivo interactions with the ECM can regulate shape, gene expression and other cell functions. The shape of the annulus cell changes markedly during life: the young, healthy disc contains spindle shaped cells and abundant collagen. With aging and degeneration, many cells assume a strikingly different appearance, become rounded and are surrounded by unusual accumulations of ECM products. In vitro manipulation of disc cells provides an experimental window for testing how disc cells from given individuals respond when they are grown in environments which direct cells to have either spindle- or rounded-shapes. In vitro assessment of the response of such cells to platelet-derived growth factor and to Matrigel™ showed a continued influence of cell shape even in the presence of a growth factor stimulus. These findings contribute new information to the important issue of the influence of cell shape on cell behavior

Imaging Electronic Correlations in Twisted Bilayer Graphene near the Magic Angle

Twisted bilayer graphene with a twist angle of around 1.1{\deg} features a pair of isolated flat electronic bands and forms a strongly correlated electronic platform. Here, we use scanning tunneling microscopy to probe local properties of highly tunable twisted bilayer graphene devices and show that the flat bands strongly deform when aligned with the Fermi level. At half filling of the bands, we observe the development of gaps originating from correlated insulating states. Near charge neutrality, we find a previously unidentified correlated regime featuring a substantially enhanced flat band splitting that we describe within a microscopic model predicting a strong tendency towards nematic ordering. Our results provide insights into symmetry breaking correlation effects and highlight the importance of electronic interactions for all filling factors in twisted bilayer graphene.Comment: Main text 9 pages, 4 figures; Supplementary Information 25 page

Divergent Roles of Clock Genes in Retinal and Suprachiasmatic Nucleus Circadian Oscillators

The retina is both a sensory organ and a self-sustained circadian clock. Gene targeting studies have revealed that mammalian circadian clocks generate molecular circadian rhythms through coupled transcription/translation feedback loops which involve 6 core clock genes, namely Period (Per) 1 and 2, Cryptochrome (Cry) 1 and 2, Clock, and Bmal1 and that the roles of individual clock genes in rhythms generation are tissue-specific. However, the mechanisms of molecular circadian rhythms in the mammalian retina are incompletely understood and the extent to which retinal neural clocks share mechanisms with the suprachiasmatic nucleus (SCN), the central neural clock, is unclear. In the present study, we examined the rhythmic amplitude and period of real-time bioluminescence rhythms in explants of retina from Per1-, Per2-, Per3-, Cry1-, Cry2-, and Clock-deficient mice that carried transgenic PERIOD2::LUCIFERASE (PER2::LUC) or Period1::luciferase (Per1::luc) circadian reporters. Per1-, Cry1- and Clock-deficient retinal and SCN explants showed weakened or disrupted rhythms, with stronger effects in retina compared to SCN. Per2, Per3, and Cry2 were individually dispensable for sustained rhythms in both tissues. Retinal and SCN explants from double knockouts of Cry1 and Cry2 were arrhythmic. Gene effects on period were divergent with reduction in the number of Per1 alleles shortening circadian period in retina, but lengthening it in SCN, and knockout of Per3 substantially shortening retinal clock period, but leaving SCN unaffected. Thus, the retinal neural clock has a unique pattern of clock gene dependence at the tissue level that it is similar in pattern, but more severe in degree, than the SCN neural clock, with divergent clock gene regulation of rhythmic period

Cosmological evolution of the Higgs boson's vacuum expectation value

We point out that the expansion of the universe leads to a cosmological time evolution of the vacuum expectation of the Higgs boson. Within the standard model of particle physics, the cosmological time evolution of the vacuum expectation of the Higgs leads to a cosmological time evolution of the masses of the fermions and of the electroweak gauge bosons while the scale of Quantum Chromodynamics (QCD) remains constant. Precise measurements of the cosmological time evolution of u=me/mp, where me and mp are respectively the electron and proton mass (which is essentially determined by the QCD scale), therefore provide a test of the standard models of particle physics and of cosmology. This ratio can be measured using modern atomic clocks

Quantitative analysis of single bacterial chemotaxis using a linear concentration gradient microchannel

A microfluidic device to quantify bacterial chemotaxis has been proposed, which generates a linear concentration gradient of chemoattractant in the main channel only by convective and molecular diffusion, and which enables the bacteria to enter the main channel in a single file by hydrodynamic focusing technique. The trajectory of each bacterium in response to the concentration gradient of chemoattractant is photographed by a CCD camera and its velocity is acquired by a simple PTV (Particle Tracking Velocimetry) algorithm. An advantage of this assay is to measure the velocity of a single bacterium and to quantify the degree of chemotaxis by analyzing the frequency of velocities concurrently. Thus, the parameter characterizing the motility of wild-type Escherichia coli strain RP437 in response to various concentration gradients of L-aspartate is obtained in such a manner that the degree of bacterial chemotaxis is quantified on the basis of a newly proposed Migration Index