Myosin VIIA is required for aminoglycoside accumulation in cochlear hair cells.

Myosin VIIA is expressed by sensory hair cells and has a primary structure predicting a role in membrane trafficking and turnover, processes that may underlie the susceptibility of hair cells to aminoglycoside antibiotics. [3H]Gentamicin accumulation and the effects of aminoglycosides were therefore examined in cochlear cultures of mice with different missense mutations in the myosin VIIA gene, Myo7a, to see whether myosin VIIA plays a role in aminoglycoside ototoxicity. Hair cells from homozygous mutant Myo7a(sh1) mice, with a mutation in a non-conserved region of the myosin VIIA head, respond rapidly to aminoglycoside treatment and accumulate high levels of gentamicin. Hair cells from homozygous mutant Myo7a(6J) mice, with a mutation at a highly conserved residue close to the ATP binding site of the myosin VIIA head, do not accumulate [3H]gentamicin and are protected from aminoglycoside ototoxicity. Hair cells from heterozygotes of both alleles accumulate [3H]gentamicin and respond to aminoglycosides. Although aminoglycoside uptake is thought to be via apical surface-associated endocytosis, coated pit numbers on the apical membrane of heterozygous and homozygous Myo7a(6J) hair cells are similar. Pulse-chase experiments with cationic ferritin confirm that the apical endocytotic pathway is functional in homozygous Myo7a(6J) hair cells. Transduction currents can be recorded from both heterozygous and homozygous Myo7a(6J) hair cells, suggesting it is unlikely that the drug enters via diffusion through the mechanotransducer channel. The results show that myosin VIIA is required for aminoglycoside accumulation in hair cells. Myosin VIIA may transport a putative aminoglycoside receptor to the hair cell surface, indirectly translocate it to sites of membrane retrieval, or retain it in the endocytotic pathway

Generation of frequency sidebands on single photons with indistinguishability from quantum dots

Generation and manipulation of the quantum state of a single photon is at the heart of many quantum information protocols. There has been growing interest in using phase modulators as quantum optics devices that preserve coherence. In this Letter, we have used an electro-optic phase modulator to shape the state vector of single photons emitted by a quantum dot to generate new frequency components (modes) and explicitly demonstrate that the phase modulation process agrees with the theoretical prediction at a single photon level. Through two-photon interference measurements we show that for an output consisting of three modes (the original mode and two sidebands), the indistinguishability of the mode engineered photon, measured through the secondorder intensity correlation (g2(0)) is preserved. This work demonstrates a robust means to generate a photonic qubit or more complex state (e.g., a qutrit) for quantum communication applications by encoding information in the sidebands without the loss of coherence

Quantum field effects in coupled atomic and molecular Bose-Einstein condensates

This paper examines the parameter regimes in which coupled atomic and molecular Bose-Einstein condensates do not obey the Gross-Pitaevskii equation. Stochastic field equations for coupled atomic and molecular condensates are derived using the functional positive-P representation. These equations describe the full quantum state of the coupled condensates and include the commonly used Gross-Pitaevskii equation as the noiseless limit. The model includes all interactions between the particles, background gas losses, two-body losses and the numerical simulations are performed in three dimensions. It is found that it is possible to differentiate the quantum and semiclassical behaviour when the particle density is sufficiently low and the coupling is sufficiently strong.Comment: 4 postscript figure

interRAI home care quality indicators

Abstract Background This paper describe the development of interRAI’s second-generation home care quality indicators (HC-QIs). They are derived from two of interRAI’s widely used community assessments: the Community Health Assessment and the Home Care Assessment. In this work the form in which the quality problem is specified has been refined, the covariate structure updated, and two summary scales introduced. Methods Two data sets were used: at the client and home-care site levels. Client-level data were employed to identify HC-QI covariates. This sample consisted of 335,544 clients from Europe, Canada, and the United States. Program level analyses, where client level data were aggregated at the site level, were also based on the clients from the samples from Europe, Canada, and the United States. There were 1,654 program-based observations – 22% from Europe, 23% from the US, and 55% from Canada. The first task was to identify potential HC-QIs, including both change and prevalence measures. Next, they were reviewed by industry representatives and members of the interRAI network. A two-step process adjustment was followed to identify the most appropriate covariance structure for each HC-QI. Finally, a factor analytic strategy was used to identify HC-QIs that cluster together and thus are candidates for summary scales. Results The set of risk adjusted HC-QIs are multi-dimensional in scope, including measures of function, clinical complexity, social life, distress, and service use. Two factors were identified. The first includes a set of eleven measures that revolve around the absence of decline. This scale talks about functional independence and engagement. The second factor, anchored on nine functional improvement HC-QIs, referenced positively, this scale indicates a return to clinical balance. Conclusions Twenty-three risk-adjusted, HC-QIs are described. Two new summary HC-QI scales, the “Independence Quality Scale” and the “Clinical Balance Quality Scale” are derived. In use at a site, these two scales can provide a macro view of local performance, offering a way for a home care agency to understand its performance. When scales perform less positively, the site then is able to review the HC-QI items that make up the scale, providing a roadmap for areas of greatest concern and in need of targeted interventions.http://deepblue.lib.umich.edu/bitstream/2027.42/112324/1/12877_2013_Article_931.pd

Permissive Controller Synthesis for Probabilistic Systems

We propose novel controller synthesis techniques for probabilistic systems modelled using stochastic two-player games: one player acts as a controller, the second represents its environment, and probability is used to capture uncertainty arising due to, for example, unreliable sensors or faulty system components. Our aim is to generate robust controllers that are resilient to unexpected system changes at runtime, and flexible enough to be adapted if additional constraints need to be imposed. We develop a permissive controller synthesis framework, which generates multi-strategies for the controller, offering a choice of control actions to take at each time step. We formalise the notion of permissivity using penalties, which are incurred each time a possible control action is disallowed by a multi-strategy. Permissive controller synthesis aims to generate a multi-strategy that minimises these penalties, whilst guaranteeing the satisfaction of a specified system property. We establish several key results about the optimality of multi-strategies and the complexity of synthesising them. Then, we develop methods to perform permissive controller synthesis using mixed integer linear programming and illustrate their effectiveness on a selection of case studies

Spectrophotometric Observations of Blue Compact Dwarf Galaxies: Mrk 370

We present results from a detailed spectrophotometric analysis of the blue compact dwarf galaxy (BCD) Mrk 370, based on deep UBVRI broad-band and Halpha narrow-band observations, and long-slit and two-dimensional spectroscopy of its brightest knots. The spectroscopic data are used to derive the internal extinction, and to compute metallicities, electronic density and temperature in the knots. By subtracting the contribution of the underlying older stellar population, modeled by an exponential function, removing the contribution from emission lines, and correcting for extinction, we can measure the true colors of the young star-forming knots. We show that the colors obtained this way differ significantly from those derived without the above corrections, and lead to different estimates of the ages and star-forming history of the knots. Using predictions of evolutionary synthesis models, we estimate the ages of both the starburst regions and the underlying stellar component. We found that we can reproduce the colors of all the knots with an instantaneous burst of star formation and the Salpeter initial mass function with an upper mass limit of 100 solar masses. The resulting ages range between 3 and 6 Myrs. The colors of the low surface brightness component are consistent with ages larger than 5 Gyr. The kinematic results suggest ordered motion around the major axis of the galaxy.Comment: 26 pages with 14 figures; accepted for publication in Ap

Spectrophotometric investigations of Blue Compact Dwarf Galaxies: Markarian 35

We present results from a detailed spectrophotometric analysis of the blue compact dwarf galaxy Mrk 35 (Haro 3), based on deep optical (B,V,R,I) and near-IR (J,H,K) imaging, Halpha narrow-band observations and long-slit spectroscopy. The optical emission of the galaxy is dominated by a central young starburst, with a bar-like shape, while an underlying component of stars, with elliptical isophotes and red colors, extends more than 4 kpc from the galaxy center. High resolution Halpha and color maps allow us to identify the star-forming regions, to spatially discriminate them from the older stars, and to recognize several dust patches. We derive colors and Halpha parameters for all the identified star-forming knots. Observables derived for each knot are corrected for the contribution of the underlying older stellar population, the contribution by emission lines, and from interstellar extinction, and compared with evolutionary synthesis models. We find that the contributions of these three factors are by no means negligible and that they significantly vary across the galaxy. Therefore, careful quantification and subtraction of emission lines, galaxy host contribution, and interstellar reddening at every galaxy position, are essential to derive the properties of the young stars in BCDs. We find that we can reproduce the colors of all the knots with an instantaneous burst of star formation and the Salpeter initial mass function with an upper mass limit of 100 M_solar. In all cases the knots are just a few Myr old. The underlying population of stars has colors consistent with being several Gyr old.Comment: 21 pages, 13 figures. Accepted for publication in ApJ, tentatively scheduled for the ApJ November 1, 2007 v669n1 issu

Systematic effects and a new determination of the primordial abundance of 4He and dY/dZ from observations of blue compact galaxies

We use spectroscopic observations of a sample of 82 HII regions in 76 blue compact galaxies to determine the primordial helium abundance Yp and the slope dY/dZ from the Y-O/H linear regression. To improve the accuracy of the dY/dZ measurement, we have included new spectrophotometric observations of 33 HII regions which span a large metallicity range, with oxygen abundance 12+log(O/H) varying between 7.43 and 8.30 (Zsun/30<Z<Zsun/4). For a subsample of 7 HII regions, we derive the He mass fraction taking into account known systematic effects, including collisional and fluorescent enhancements of HeI emission lines, collisional excitation of hydrogen emission, underlying stellar HeI absorption and the difference between the temperatures Te(HeII) in the He^+ zone and Te(OIII) derived from the collisionally excited [OIII] lines. We find that the net result of all the systematic effects combined is small, changing the He mass fraction by less than 0.6%. By extrapolating the Y vs. O/H linear regression to O/H=0 for 7 HII regions of this subsample, we obtain Yp=0.2421+/-0.0021 and dY/dO=5.7+/-1.8, which corresponds to dY/dZ=3.7+/-1.2, assuming the oxygen mass fraction to be O=0.66Z. In the framework of the standard Big Bang nucleosynthesis theory, this Yp corresponds to Omega_b h^2 = 0.012^+0.003_-0.002, where h is the Hubble constant in units of 100 km/s/Mpc. This is smaller at the 2sigma level than the value obtained from recent deuterium abundance and microwave background radiation measurements. The linear regression slope dY/dO=4.3+/-0.7 (corresponding to dY/dZ=2.8+/-0.5) for the whole sample of 82 HII regions is similar to that derived for the subsample of 7 HII regions, although it has a considerably smaller uncertainty.Comment: 53 pages, 3 Postscript figures, accepted for publication in the Astrophysical Journa