1,702 research outputs found
Popper's Thought Experiment Reinvestigated
Popper's original thought experiment probed some fundamental and subtle rules
of quantum mechanics. Two experiments have directly and indirectly tested
Popper's hypothesis, but they seem to give contrasting results. The equations
governing these two experiments and Popper's thought experiment will be derived
from basic quantum principles. The experimental constants will be inputted and
it will show that the two experiments agree with each other and with quantum
theory
Aminoglycoside-Induced Phosphatidylserine Externalization in Sensory Hair Cells Is Regionally Restricted, Rapid, and Reversible
The aminophospholipid phosphatidylserine (PS) is normally restricted to the inner leaflet of the plasma membrane. During certain cellular processes, including apoptosis, PS translocates to the outer leaflet and can be labeled with externally applied annexin V, a calcium-dependent PS-binding protein. In mouse cochlear cultures, annexin V labeling reveals that the aminoglycoside antibiotic neomycin induces rapid PS externalization, specifically on the apical surface of hair cells. PS externalization is observed within ~75 s of neomycin perfusion, first on the hair bundle and then on membrane blebs forming around the apical surface. Whole-cell capacitance also increases significantly within minutes of neomycin application, indicating that blebbing is accompanied by membrane addition to the hair cell surface. PS externalization and membrane blebbing can, nonetheless, occur independently. Pretreating hair cells with calcium chelators, a procedure that blocks mechanotransduction, or overexpressing a phosphatidylinositol 4,5-biphosphate (PIP2)-binding pleckstrin homology domain, can reduce neomycin-induced PS externalization, suggesting that neomycin enters hair cells via transduction channels, clusters PIP2, and thereby activates lipid scrambling. The effects of short-term neomycin treatment are reversible. After neomycin washout, PS is no longer detected on the apical surface, apical membrane blebs disappear, and surface-bound annexin V is internalized, distributing throughout the supranuclear cytoplasm of the hair cell. Hair cells can therefore repair, and recover from, neomycin-induced surface damage. Hair cells lacking myosin VI, a minus-end directed actin-based motor implicated in endocytosis, can also recover from brief neomycin treatment. Internalized annexin V, however, remains below the apical surface, thereby pinpointing a critical role for myosin VI in the transport of endocytosed material away from the periphery of the hair cell
Motion of vortices in type II superconductors
The methods of formal asymptotics are used to examine the behaviour of a system of curvilinear vortices in a type II superconductor as the thickness of the vortex cores tends to zero. The vortices then appear as singularities in the field equation and are analagous to line vortices in inviscid hydrodynamics. A local analysis near each vortex core gives an equation of motion governing the evolution of these singularities
Protecting mammalian hair cells from aminoglycoside-toxicity: assessing phenoxybenzamine’s potential
Aminoglycosides (AGs) are widely used antibiotics because of their low cost and high efficacy against gram-negative bacterial infection. However, AGs are ototoxic,causing the death of sensory hair cells in the inner ear. Strategies aimed at developing or discovering agents that protect against aminoglycoside ototoxicity have focused on inhibiting apoptosis or more recently, on preventing antibiotic uptake by the hair cells. Recent screens for ototoprotective compounds using the larval zebrafish lateral line identified phenoxybenzamine as a potential protectant for aminoglycoside induced hair cell death. Here we used live imaging of FM1-43 uptake as a proxy for aminoglycoside entry, combined with hair-cell death assays to evaluate whether phenoxybenzamine can protect mammalian cochlear hair cells from the deleterious effects of the aminoglycoside antibiotic neomycin. We show that phenoxybenzamine can block FM1-43 entry into mammalian hair cells in a reversible and dose-dependent manner, but pre-incubation is required for maximal inhibition of entry. We observed differential effects of phenoxybenzamine on FM1-43 uptake in the two different types of cochlear hair cell in mammals, the outer hair cells (OHCs) and inner hair cells (IHCs).The requirement for pre-incubation and reversibility suggests an intracellular rather than an extracellular site of action for phenoxybenzamine. We also tested the efficacy of phenoxybenzamine as an otoprotective agent. In mouse cochlear explants the hair cell death resulting from 24 h exposure to neomycin was steeply dose-dependent, with 50% cell death occurring at ~230 uM for both IHC and OHC. We used 250 uM neomycin in subsequent hair-cell death assays. At 100 uM with 1 h pre-incubation, phenoxybenzamine conferred significant protection to both IHCs and OHCs, however at higher concentrations phenoxybenzamine itself showed clear signs of ototoxicity and an additive toxic effect when combined with neomycin. These data do not support the use of phenoxybenzamine as a therapeutic agent in mammalian inner ear. Our findings do share parallels with the observations from the zebrafish lateral line model but they also highlight the necessity for validation in the mammalian system and the potential for differential effects on sensory hair cells from different species, in different systems and even between cells in the same organ
Porosity Controls Spread of Excitation in Tectorial Membrane Traveling Waves
Cochlear frequency selectivity plays a key role in our ability to understand speech, and is widely believed to be associated with cochlear amplification. However, genetic studies targeting the tectorial membrane (TM) have demonstrated both sharper and broader tuning with no obvious changes in hair bundle or somatic motility mechanisms. For example, cochlear tuning of Tectb[superscript –/–] mice is significantly sharper than that of Tecta[superscript Y1870C/+] mice, even though TM stiffnesses are similarly reduced relative to wild-type TMs. Here we show that differences in TM viscosity can account for these differences in tuning. In the basal cochlear turn, nanoscale pores of Tecta[superscript Y1870C/+] TMs are significantly larger than those of Tectb[superscript –/–] TMs. The larger pore size reduces shear viscosity (by ∼70%), thereby reducing traveling wave speed and increasing spread of excitation. These results demonstrate the previously unrecognized importance of TM porosity in cochlear and neural tuning.National Institutes of Health (U.S.) (Grant R01-DC00238)National Science Foundation (U.S.). Graduate Research Fellowship Program (Grant 1122374)National Institutes of Health (U.S.) (Training Grant
Modelling the effect of gap junctions on tissue-level cardiac electrophysiology
When modelling tissue-level cardiac electrophysiology, continuum
approximations to the discrete cell-level equations are used to maintain
computational tractability. One of the most commonly used models is represented
by the bidomain equations, the derivation of which relies on a homogenisation
technique to construct a suitable approximation to the discrete model. This
derivation does not explicitly account for the presence of gap junctions
connecting one cell to another. It has been seen experimentally [Rohr,
Cardiovasc. Res. 2004] that these gap junctions have a marked effect on the
propagation of the action potential, specifically as the upstroke of the wave
passes through the gap junction.
In this paper we explicitly include gap junctions in a both a 2D discrete
model of cardiac electrophysiology, and the corresponding continuum model, on a
simplified cell geometry. Using these models we compare the results of
simulations using both continuum and discrete systems. We see that the form of
the action potential as it passes through gap junctions cannot be replicated
using a continuum model, and that the underlying propagation speed of the
action potential ceases to match up between models when gap junctions are
introduced. In addition, the results of the discrete simulations match the
characteristics of those shown in Rohr 2004. From this, we suggest that a
hybrid model -- a discrete system following the upstroke of the action
potential, and a continuum system elsewhere -- may give a more accurate
description of cardiac electrophysiology.Comment: In Proceedings HSB 2012, arXiv:1208.315
The Parallel Complexity of Growth Models
This paper investigates the parallel complexity of several non-equilibrium
growth models. Invasion percolation, Eden growth, ballistic deposition and
solid-on-solid growth are all seemingly highly sequential processes that yield
self-similar or self-affine random clusters. Nonetheless, we present fast
parallel randomized algorithms for generating these clusters. The running times
of the algorithms scale as , where is the system size, and the
number of processors required scale as a polynomial in . The algorithms are
based on fast parallel procedures for finding minimum weight paths; they
illuminate the close connection between growth models and self-avoiding paths
in random environments. In addition to their potential practical value, our
algorithms serve to classify these growth models as less complex than other
growth models, such as diffusion-limited aggregation, for which fast parallel
algorithms probably do not exist.Comment: 20 pages, latex, submitted to J. Stat. Phys., UNH-TR94-0
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