10,295 research outputs found

    Maturation of NaV and KV channel topographies in the auditory nerve spike initiator before and after developmental onset of hearing function

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    Auditory nerve excitation and thus hearing depend on spike-generating ion channels and their placement along the axons of auditory nerve fibers (ANFs). The developmental expression patterns and native axonal locations of voltage-gated ion channels in ANFs are unknown. Therefore, we examined the development of heminodes and nodes of Ranvier in the peripheral axons of type I ANFs in the rat cochlea with immunohistochemistry and confocal microscopy. Nodal structures presumably supporting presensory spiking formed between postnatal days 5 (P5) and P7, including Ankyrin-G, NaV1.6, and Caspr. These immature nodal structures lacked low-voltage-activated KV1.1 which was not enriched at juxtaparanodes until approximately P13, concurrent with the developmental onset of acoustic hearing function. Anatomical alignment of ANF spike-initiating heminodes relative to excitatory input from inner hair cell (IHC) ribbon synapses continued until approximately P30. High-voltage-activated KV3.1b and KV2.2 were expressed in mutually exclusive domains: KV3.1b was strictly localized to nodes and heminodes, whereas KV2.2 expression began at the juxtaparanodes and continued centrally along the first internode. At spike-initiating heminodes in the distal osseous spiral lamina, NaV1.1 partly overlapped NaV1.6 and ankyrin-G. ANFs displayed KV7.2 and KV7.3 at heminodes, nodes, internodes, and the unmyelinated synaptic terminal segments beneath IHCs in the organ of Corti. In response to sound, spikes are initiated at the heminode, which is tightly coupled to the IHC ribbon synapse ∼20–40 μm away. These results show that maturation of nodal alignment and ion channel content may underlie postnatal improvements of ANF excitability and discharge synchrony.SIGNIFICANCE STATEMENTAcoustic and electrical hearing depends on rapid, reliable, and precise spike generation in auditory nerve fibers. A limitation of current models and therapies is a lack of information on the identities and topographies of underlying ion channels. We report the developmental profile of the auditory nerve spike generator with a focus on NaV1.1, NaV1.6, KV1.1, KV2.2, KV3.1b, KV7.2, and KV7.3 in relation to the scaffold ankyrin-G. Molecular anatomy of the spike generator matures in the weeks after developmental onset of hearing function. Subcellular positioning of voltage-gated ion channels will enable multicompartmental modeling of auditory nerve responses elicited by afferent chemical neurotransmission from hair cells and modulated by efferent neurotransmitters or evoked by extracellular field stimulation from a cochlear implant.</jats:p


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    The Smooth Greensnake (Opheodrys vernalis) is a small, slender, oviparous, colubrid snake that is widely distributed in North America. Nonetheless, there have been few studies on this species, and little is known about Canadian populations. The objective of this study was to examine morphology, reproduction, seasonal activity and habitat use of a northern population of the Smooth Greensnake. Individuals were captured during the summers of 2007-2010 in southwestern Manitoba, Canada. Females were larger and relatively heavier than males, but clutch size did not consistently increase with body size. In addition, 59% (on average) of available adult females were gravid in any given year, suggesting that females may not reproduce each year. Males had relatively longer heads and longer tails than females. Males were more common in early August; otherwise, females were more common. The peak of male activity in August suggests that fall mating might occur in this species, but this was not confirmed. Finally, Smooth Greensnakes were most commonly found in grassland, and there were no differences in habitat use between the sexes. Further research on northern populations of Smooth Greensnakes would provide valuable information on this little-studied species

    The Impacts of Contract Type on Broker Performance: Submarket Effects

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    Rutherford et al. (2001) develop and empirically test a model that analyzes the effect the type of listing contract, either exclusive agency (EA) or exclusive right to sell (ERTS), has on the performance of the agent/broker. This paper extends the work of Rutherford et al. (2001) and looks at differences between housing submarkets delineated by price. The results show a selling price discount associated with both broker-effected and owner-effected sales for lower-priced houses with EA contracts. For higher-priced houses, there is no price advantage to an EA-listing if the broker achieves the sale, but if the owner sells the house, there is a modest price premium associated with the sale. The primary implication of the results is that owners of lower-priced houses should be wary of alternative listing arrangements, namely exclusive agency contracts.

    Discussion of: A statistical analysis of multiple temperature proxies: Are reconstructions of surface temperatures over the last 1000 years reliable?

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    Discussion of "A statistical analysis of multiple temperature proxies: Are reconstructions of surface temperatures over the last 1000 years reliable?" by B.B. McShane and A.J. Wyner [arXiv:1104.4002]Comment: Published in at http://dx.doi.org/10.1214/10-AOAS398F the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

    Electronic effects in radiation damage simulations in metals

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    Radiation damage has traditionally been modelled using classical molecular dynamics, in which the role of the electrons is con�fined to describing bonding via the interatomic potential. This is generally sufficient for low radiation energies. However high energy atoms lose a signi�ficant proportion of their energy to electronic excitations, therefore a simulation of the relaxation of a metallic lattice after a high energy event requires a description of the energetic interaction between atoms and electrons. The mechanisms of inelastic collisions between electrons and ions, coupling between electrons and phonons and the di�ffusion of energy through the electronic system to the rest of the lattice become signfi�cant. We have coupled large scale MD simulations of the lattice to a continuum model for the electronic temperature evolution. Energy lost by the atoms due to elastic and inelastic electronic collisions is gained by the electronic system and evolves according to a heat di�ffusion equation. The electronic energy is coupled to the lattice via a modifi�ed Langevin thermostat, representing electron-phonon coupling. Results of the simulation of both displacement cascades and ion tracks, representing the low and high extremes of incident ion energy respectively, are presented. The eff�ect of annealing of pre-existing damage by electronic excitation is studied and the behaviour under swift heavy ion irradiation in iron and tungsten is compared. In simulations of displacement cascades, the strength of coupling between the atoms and electrons emerges as the main parameter determining residual damage. Our new methodology gives rise to reduced damage compared to traditional methods in all cases. Ion track simulations demonstrated that the relaxation dynamics, and hence the residual damage, was dependent on the magnitude and temperature dependence of the electronic thermal parameters

    Effects of a falls exercise intervention on strength, power, functional ability and bone in older frequent fallers: FaME (Falls Management Exercise) RCT secondary analysis

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    OBJECTIVES: Falls Management Exercise (FaME) has been shown to reduce falls in frequent fallers and in lower risk sedentary older people. The effects of FaME on the strength, power, physical function and bone health of frequently falling older women are yet to be established. METHODS: This paper reports secondary analysis of data from the original randomised controlled trial of FaME in 100 community dwelling women aged ≥65 years with a history of ≥3 falls in the previous year. Intervention was group delivered, weekly one hour tailored dynamic balance and strength exercise classes and home exercise for nine months. OUTCOME MEASURES INCLUDED: strength (handgrip, quadriceps, hamstrings, hip abductors, ankles), lower limb explosive power and functional tests (timed up and go, functional reach, timed floor rise and balance), analysed using Linear Mixed Model analysis. Bone Mineral Density (BMD) at hip and spine was measured in a smaller sub-group and analysed using t-tests. RESULTS: Significant time*group interactions in all measures of strength, except isometric ankle dorsiflexion, concentric hamstring and eccentric quadriceps strength. These improvements in strength equated to average improvements of 7-45%. There were also significant improvements in explosive power (W/kg) (18%, p=0.000), timed up and go (16%, p=0.000), functional reach (17%, p=0.000), floor rise (10%, p=0.002) and eyes closed static balance (56%, p=0.000). There was a significant loss of hip BMD in the control group (neck of femur p&lt;0.05; ward's triangle p&lt;0.02). CONCLUSION: The FaME intervention improves lower limb strength, power and clinically relevant functional outcomes in frequently falling older women

    P/6 The water oxidizing enzyme

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    Market Structure in the Residential Real Estate Brokerage Market

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    This study provides empirical evidence regarding brokerage firm concentration in a local market multiple listing service setting over the year 1992-1995. To evaluate the level of brokerage firm concentration in this market, Gini Coefficients, Herfindahl-Hirschman Indices and Concentration Ratios for each year of the study period are calculated. Our results indicate that for firms responsible for listing properties, firm concentration has not varied substantially over the four-year study period. However, for those firms that were responsible for actually selling properties, firm concentration has decreased over the study period. This finding tends to indicate that the MLS now provides greater exposure to a wide variety of sales firms, therefore leading to a higher level of competition with a lower level of concentration for selling firms in this local market.

    Real Estate Agent Remarks: Help or Hype?

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    This article groups the remarks of a multiple listing service listing into common themes and then uses a hedonic pricing model to determine whether such comments are priced in a meaningful way. The comments provide information on the motivation of the seller, location of the property and physical improvements or defects. Most of the comments analyzed are statistically significant. Negative comments are associated with lower sales prices suggesting the helpful nature of comments. Some of the positive comments, however, including "new paint" and "good location" are also associated with lower sales prices suggesting that some comments may be better classified as hype.