Model-based prediction of optogenetic sound encoding in the human cochlea by future optical cochlear implants

When hearing fails, electrical cochlear implants (eCIs) partially restore hearing by direct stimulation of spiral ganglion neurons (SGNs). As light can be better confined in space than electrical current, optical CIs (oCIs) provide more spectral information promising a fundamental improvement of hearing restoration by cochlear implants. Here, we turned to computer modelling for predicting the outcome of optogenetic hearing restoration by future oCIs in humans. We combined three-dimensional reconstruction of the human cochlea with ray-tracing simulation of emission from LED or laser-coupled waveguide emitters of the oCI. Irradiance was read out at the somata of SGNs. The irradiance values reached with waveguides were about 14 times higher than with LEDs, at the same radiant flux of the emitter. Moreover, waveguides outperformed LEDs regarding spectral selectivity. oCIs with either emitter type showed greater spectral selectivity when compared to eCI. In addition, modeling the effects of the source-to-SGN distance, orientation of the sources and impact of scar tissue further informs the development of optogenetic hearing restoration

Hermitian Young Operators

Starting from conventional Young operators we construct Hermitian operators which project orthogonally onto irreducible representations of the (special) unitary group.Comment: 15 page

Semiclassical Approach to Parametric Spectral Correlation with Spin 1/2

The spectral correlation of a chaotic system with spin 1/2 is universally described by the GSE (Gaussian Symplectic Ensemble) of random matrices in the semiclassical limit. In semiclassical theory, the spectral form factor is expressed in terms of the periodic orbits and the spin state is simulated by the uniform distribution on a sphere. In this paper, instead of the uniform distribution, we introduce Brownian motion on a sphere to yield the parametric motion of the energy levels. As a result, the small time expansion of the form factor is obtained and found to be in agreement with the prediction of parametric random matrices in the transition within the GSE universality class. Moreover, by starting the Brownian motion from a point distribution on the sphere, we gradually increase the effect of the spin and calculate the form factor describing the transition from the GOE (Gaussian Orthogonal Ensemble) class to the GSE class.Comment: 25 pages, 2 figure

Is there an unmet medical need for improved hearing restoration?

Hearing impairment, the most prevalent sensory deficit, affects more than 466 million people worldwide (WHO). We presently lack causative treatment for the most common form, sensorineural hearing impairment; hearing aids and cochlear implants (CI) remain the only means of hearing restoration. We engaged with CI users to learn about their expectations and their willingness to collaborate with health care professionals on establishing novel therapies. We summarize upcoming CI innovations, gene therapies, and regenerative approaches and evaluate the chances for clinical translation of these novel strategies. We conclude that there remains an unmet medical need for improving hearing restoration and that we are likely to witness the clinical translation of gene therapy and major CI innovations within this decade

Semiclassical Time Evolution and Trace Formula for Relativistic Spin-1/2 Particles

We investigate the Dirac equation in the semiclassical limit \hbar --> 0. A semiclassical propagator and a trace formula are derived and are shown to be determined by the classical orbits of a relativistic point particle. In addition, two phase factors enter, one of which can be calculated from the Thomas precession of a classical spin transported along the particle orbits. For the second factor we provide an interpretation in terms of dynamical and geometric phases.Comment: 8 pages, no figure

Zitterbewegung and semiclassical observables for the Dirac equation

In a semiclassical context we investigate the Zitterbewegung of relativistic particles with spin 1/2 moving in external fields. It is shown that the analogue of Zitterbewegung for general observables can be removed to arbitrary order in \hbar by projecting to dynamically almost invariant subspaces of the quantum mechanical Hilbert space which are associated with particles and anti-particles. This not only allows to identify observables with a semiclassical meaning, but also to recover combined classical dynamics for the translational and spin degrees of freedom. Finally, we discuss properties of eigenspinors of a Dirac-Hamiltonian when these are projected to the almost invariant subspaces, including the phenomenon of quantum ergodicity

Semiclassical Approach to Chaotic Quantum Transport

We describe a semiclassical method to calculate universal transport properties of chaotic cavities. While the energy-averaged conductance turns out governed by pairs of entrance-to-exit trajectories, the conductance variance, shot noise and other related quantities require trajectory quadruplets; simple diagrammatic rules allow to find the contributions of these pairs and quadruplets. Both pure symmetry classes and the crossover due to an external magnetic field are considered.Comment: 33 pages, 11 figures (appendices B-D not included in journal version

Magnetotransport in Two-Dimensional Electron Systems with Spin-Orbit Interaction

We present magnetotransport calculations for homogeneous two-dimensional electron systems including the Rashba spin-orbit interaction, which mixes the spin-eigenstates and leads to a modified fan-chart with crossing Landau levels. The quantum mechanical Kubo formula is evaluated by taking into account spin-conserving scatterers in an extension of the self-consistent Born approximation that considers the spin degree of freedom. The calculated conductivity exhibits besides the well-known beating in the Shubnikov-de Haas (SdH) oscillations a modulation which is due to a suppression of scattering away from the crossing points of Landau levels and does not show up in the density of states. This modulation, surviving even at elevated temperatures when the SdH oscillations are damped out, could serve to identify spin-orbit coupling in magnetotransport experiments. Our magnetotransport calculations are extended also to lateral superlattices and predictions are made with respect to 1/B periodic oscillations in dependence on carrier density and strength of the spin-orbit coupling.Comment: 8 pages including 8 figures; submitted to PR

PD-1 checkpoint inhibition enhances the antilymphoma activity of CD19-CAR-iNKT cells that retain their ability to prevent alloreactivity.

Relapse and graft-versus-host disease (GVHD) are the main causes of death after allogeneic hematopoietic cell transplantation (HCT). Preclinical murine models and clinical data suggest that invariant natural killer T (iNKT) cells prevent acute and chronic GVHD. In addition, iNKT cells are crucial for efficient immune responses against malignancies and contribute to reduced relapse rates after transplantation. Chimeric antigen receptors (CAR) redirect effector cells to cell surface antigens and enhance killing of target cells. With this study, we aimed to combine enhanced cytotoxicity of CD19-CAR-iNKT cells against lymphoma cells with their tolerogenic properties. iNKT cells were isolated from peripheral blood mononuclear cells and transduced with an anti-CD19-CAR retrovirus. After in vitro expansion, the functionality of CD19-CAR-iNKT cells was assessed by flow cytometry, image stream analysis and multiplex analysis in single-stimulation or repeated-stimulation assays. Moreover, the immunoregulatory properties of CD19-CAR-iNKT cells were analyzed in apoptosis assays and in mixed lymphocyte reactions. The effect of checkpoint inhibition through nivolumab was analyzed in these settings. In this study, we could show that the cytotoxicity of CD19-CAR-iNKT cells was mediated either through engagement of their CAR or their invariant T-cell receptor, which may circumvent loss of response through antigen escape. However, encounter of CD19-CAR-iNKT cells with their target induced a phenotype of exhaustion. Consequently, checkpoint inhibition increased cytokine release, cytotoxicity and survival of CD19-CAR-iNKT cells. Additionally, they showed robust suppression of alloreactive immune responses. In this work, we demonstrate that CAR-iNKT cells are a powerful cytotherapeutic option to prevent or treat relapse while potentially reducing the risk of GVHD after allogeneic HCT

Spin Orientation and Spin Precession in Inversion-Asymmetric Quasi Two-Dimensional Electron Systems

Inversion asymmetry induced spin splitting of the electron states in quasi two-dimensional (2D) systems can be attributed to an effective magnetic field B which varies in magnitude and orientation as a function of the in-plane wave vector k||. Using a realistic 8x8 Kane model that fully takes into account spin splitting because of both bulk inversion asymmetry and structure inversion asymmetry we investigate the spin orientation and the effective field B for different configurations of a quasi 2D electron system. It is shown that these quantities depend sensitively on the crystallographic direction in which the quasi 2D system was grown as well as on the magnitude and orientation of the in-plane wave vector k||. These results are used to discuss how spin-polarized electrons can precess in the field B(k||). As a specific example we consider GaInAs-InP quantum wells.Comment: 10 pages, 6 figure