Estimation of the ear canal displacement field due to in-ear device insertion using a registration method on a human-like artificial ear.

Passive and active in-ear devices (IED) occluding the ear canal are commonly used to (i) protect people from high noise levels (earplugs), (ii) assist people suffering from hearing impairment (hearing aids) or (iii) help people in listening from their sound systems (earbuds). However, the usability and/or efficiency of IEDs can be greatly affected by several discomfort components (physical, acoustical and functional). The mechanical pressure exerted by the IED onto the ear canal walls is greatly suspected to affect the aforementioned comfort components. This physical characteristic is closely related to the displacement field induced by the IED insertion, which has to be known for a better understanding of perceived discomfort. Thus, this paper proposes to validate a method based on medical images to estimate the displacement field of the ear canal walls due to the insertion of an IED. The approach is validated on a human-like artificial ear with canal geometry deformed using two custom molded IEDs with controlled shapes. These geometries are obtained using computed tomography imaging and the displacement field is computed using a registration method. The errors due to the ear canal segmentation and to the registration steps are small enough to compute a relevant estimation of the expected displacement field. Results show that the amplitude of the displacement and its location into the ear canal can be evaluated with an accuracy of ±â€¯0.2 mm and ±â€¯0.4 mm respectively. Preliminary results on images with a degraded resolution indicate that the proposed approach used to assess the displacement field of the ear canal walls using computed tomography images could be applied on magnetic resonance images, which is a preferred method to image human subject ear canals for future investigations.

Prediction of the sound field above a patchwork of absorbing materials.

The aim of this paper is to investigate the acoustic performance of sound absorbing materials through a numerical wave based prediction technique. The final goal of this work is to get insight into the acoustic behavior of a combination of sound absorbing patches. In order to address a wide frequency range, a model based on the Trefftz approach is adopted. In this approach, the dynamic field variables are expressed in terms of global wave function expansions that satisfy the governing dynamic equations exactly. Therefore, approximation errors are associated only with the boundary conditions of the considered problem. This results in a computationally efficient technique. The main advantage of this method is the fact that the sound absorbing patches do not have to be locally reacting. In this article, the wave based method is described and experimentally validated for the case of normal incidence sound absorption identification in a standing wave tube. Afterwards, the method is applied to simulate some interesting setups of absorbing materials.

Investigation of the convergence of the mixed displacement-pressure formulation for three-dimensional poroelastic materials using hierarchical elements.

Recently, a mixed pressure displacement [u, P] formulation based on Biot's poroelasticity equations has been presented for porous materials. This model leads to a reduction of the number of degrees of freedom required for the modeling of three-dimensional porous media in comparison to classical displacement-displacement [u, U] formulations. In this paper, an extension of the [u, P] formulation based on hierarchical elements is presented. First, a variant of the weak integral form of the [u, P] formulation is presented and its numerical implementation using hierarchical elements is detailed, together with the application of boundary and loading conditions. Numerical results are presented to show the accuracy and performance of the present approach. In particular, the importance of correctly capturing the coupling effects between the two phases is highlighted.

SSR591813, a novel selective and partial alpha4beta2 nicotinic receptor agonist with potential as an aid to smoking cessation.

(5aS,8S,10aR)-5a,6,9,10-Tetrahydro,7H,11H-8,10a-methanopyrido[2',3':5,6]pyrano[2,3-d]azepine (SSR591813) is a novel compound that binds with high affinity to the rat and human alpha4beta2 nicotinic acetylcholine receptor (nAChR) subtypes (Ki = 107 and 36 nM, respectively) and displays selectivity for the alpha4beta2 nAChR (Ki, human alpha3beta4 > 1000, alpha3beta2 = 116; alpha1beta1deltagamma > 6000 nM and rat alpha7 > 6000 nM). Electrophysiological experiments indicate that SSR591813 is a partial agonist at the human alpha4beta2 nAChR subtype (EC50 = 1.3 micro M, IA =19% compared with the full agonist 1,1-dimethyl-4-phenyl-piperazinium). In vivo findings from microdialysis and drug discrimination studies confirm the partial intrinsic activity of SSR591813. The drug increases dopamine release in the nucleus accumbens shell (30 mg/kg i.p.) and generalizes to nicotine or amphetamine (10-20 mg/kg i.p.) in rats, with an efficacy approximately 2-fold lower than that of nicotine. Pretreatment with SSR591813 (10 mg/kg i.p.) reduces the dopamine-releasing and discriminative effects of nicotine. SSR591813 shows activity in animal models of nicotine dependence at doses devoid of unwanted side effects typically observed with nicotine (hypothermia and cardiovascular effects). The compound (10 mg/kg i.p.) also prevents withdrawal signs precipitated by mecamylamine in nicotine-dependent rats and partially blocks the discriminative cue of an acute precipitated withdrawal. SSR591813 (20 mg/kg i.p.) reduces i.v. nicotine self-administration and antagonizes nicotine-induced behavioral sensitization in rats. The present results confirm important role for alpha4beta2 nAChRs in mediating nicotine dependence and suggest that SSR591813, a partial agonist at this particular nAChR subtype, may have therapeutic potential in the clinical management of smoking cessation.

Regulation of ATP-sensitive potassium channel mRNA expression in rat kidney following ischemic injury.

ATP-sensitive potassium (K(ATP)) channels are involved in the regulation of potassium homeostasis in kidneys. In the event of renal ischemia, they are thought to contribute to the important intracellular potassium loss observed in proximal tubules and thus to hypoxic injury. We have analyzed the transcriptional regulation of K(ATP) genes in rat kidney following transient renal ischemia. We observed that mRNA expression level was down-regulated for Kir1.1 and Kir4.1 potassium channels between 24 and 120 h after ischemia. In contrast, a strong increase in mRNA expression was observed for Kir6.1 shortly (2-6 h) after ischemia. Thus, renal ischemia followed by reperfusion provokes differential regulation of K(ATP) channel gene expression.

Diminution of nicotinic receptor alpha 3 subunit mRNA expression in aged rat brain.

Losses in nicotinic acetylcholine receptors (nAChRs) have been linked to a decline in cognitive function in patients with neurodegenerative diseases, but the impact of normal aging on the different neuronal nicotinic receptor subunits has yet to be fully characterized. The expression pattern of nine nAChR subunits mRNA (alpha2-7 and beta2-4) was investigated in this study in young and aged rat brains, 5 weeks and 30 months old, respectively. Microtissue samples were dissected from brain slices and nAChR subunit mRNA expression was analyzed by reverse transcription polymerase chain reaction (RT-PCR) from eight different brain areas. In several regions, a loss of PCR signal was found for the alpha3, and to a lesser extent, for alpha2 subunit mRNA in aged rat brain. A relative quantification of alpha3 and alpha4 mRNA expression was then carried out in four of these brain regions. A significant diminution of alpha3 expression level was observed in all regions tested while, in comparison, much less modification in alpha4 mRNA was detected. This decrease in alpha3 subunit mRNA may represent a selective degradation of neurons expressing the alpha3 subunit or a diminution of alpha3-containing nAChR subtypes in those neurons during aging.

Nicotinic acetylcholine subunit mRNA expression in dopaminergic neurons of the rat substantia nigra and ventral tegmental area.

The molecular composition of the nicotinic acetylcholine receptors (nAChRs) located on dopaminergic neurons and modulating their activity is unclear. Using the reverse transcriptase-polymerase chain reaction we have analyzed the mRNA for nAChR subunits expressed in the substantia nigra (SN) and ventral tegmental area (VTA) following unilateral 6-hydroxydopamine lesion of the dopaminergic system. In contrast to the unlesioned hemisphere, no signal was found in the lesioned hemisphere for alpha3, alpha5, alpha6 and beta4 subunits in the SN nor for alpha2, alpha3, alpha5, alpha6, alpha7 and beta4 subunits in the VTA, indicating the expression of these subunits in dopaminergic neurons. mRNA for alpha4, beta2 and beta3 subunits (and alpha7 in the SN) were still detected after lesion, suggesting that they are expressed in GABAergic neurons and interneurons of these brain areas. These results demonstrate the selective localisation of a number of nAChR subunit mRNA within dopaminergic neurons, strongly suggesting that a heterogenous population of nAChRs play a role in modulating dopaminergic neuronal activity.

Cloning and functional characterisation of two novel nicotinic acetylcholine receptor alpha subunits from the insect pest Myzus persicae.

Nicotinic acetylcholine receptors play a major role in excitatory neurotransmission in insect CNSs and constitute an important target for insecticides. Here, we report the isolation and functional characterisation of two cDNAs encoding nicotinic acetylcholine receptor alpha subunits from a major insect pest, the peach-potato aphid Myzus persicae. These two subunits, termed Mp alpha1 and Mp alpha2, are respective structural homologues of the Drosophila D alpha2/Schistocerca gregaria alphaL1 alpha-subunit pair and the Drosophila ALS alpha subunit. Xenopus oocyte expression confirmed that each Myzus subunit can form functional acetylcholine- or nicotine-gated channels. However, some electrophysiological and pharmacological properties of the Myzus subunits were distinct from those encoded by the corresponding Drosophila subunits. Coexpression of the Myzus subunits with the chick beta2 subunit revealed other differences from the Drosophila system, as only very limited potentiation of agonist-induced currents was observed with Mp alpha2 and none with Mp alpha1. Available data therefore indicate that structurally homologous insect nicotinic acetylcholine receptor alpha subunits from different species can exhibit distinctive physiological and pharmacological characteristics.

Evidence for 5-HT1D beta but not 5-HT1D alpha receptor subtype expression in canine large coronary arteries and saphenous vein.

OBJECTIVE: 5-Hydroxytryptamine1D (5-HT1D) receptors are believed to play a major role in the vasoconstriction of vascular smooth muscle in human coronary arteries. However, unequivocal evidence as to which subtype of this receptor (5-HT1D alpha or 5-HT1D beta) is involved in these vasoconstrictory effects is lacking. The aim of this study was to identify in the dog the 5-HT1D receptor subtype encoding mRNAs expressed in several large coronary arteries and in the saphenous vein. METHODS: Degenerate oligonucleotide primers that selectively recognized only mammalian 5-HT1D alpha and 5-HT1D beta receptor sequences were used in RT-PCR experiments to study 5-HT1D receptor subtype expression in endothelium-denuded saphenous vein and large coronary arteries from beagle and alsatian dogs. Resulting PCR products were analysed and identified by Southern blots and sequencing. RESULTS: An identical PCR product whose sequence closely resembles that of the human 5-HT1D beta receptor (98% amino acid identity) was obtained from reverse-transcribed RNA isolated from either saphenous vein or coronary arteries, irrespective of dog race. Absence of 5-HT1D alpha expression was confirmed by Southern blot analysis. Control experiments using canine genomic DNA as template illustrated, nonetheless, that the primers chosen could amplify both 5-HT1D alpha and 5-HT1D beta sequences. CONCLUSION: Using RT-PCR, we isolated from dog vascular smooth muscle a cDNA fragment whose nucleotide sequence would encode a previously-unreported canine homologue of the 5-HT1D beta receptor. We illustrated that this subtype is the only 5-HT1D receptor subtype expressed in dog saphenous vein and large coronary arteries. The implications of these findings are discussed in light of results from functional studies of 5-HT1-like receptor-mediated effects in these canine blood vessels.

ALS and SAD-like nicotinic acetylcholine receptor subunit genes are widely distributed in insects.

Segments of nicotinic acetylcholine receptor alpha subunit genes have been isolated from a panel of insect species by polymerase chain reaction, using degenerate oligonucleotide primers designed to recognize conserved regions of the Drosophila melanogaster ALS and SAD genes. The amplified segments encode elements of typical alpha-subunits anticipated to play roles in ligand binding and ion channel formation. Each is also clearly either ALS or SAD-like. The predicted protein sequences display extremely high levels of conservation (over 85% for each subtype) even though derived from very distantly related insect species.