AERO: Audio Super Resolution in the Spectral Domain

We present AERO, a audio super-resolution model that processes speech and music signals in the spectral domain. AERO is based on an encoder-decoder architecture with U-Net like skip connections. We optimize the model using both time and frequency domain loss functions. Specifically, we consider a set of reconstruction losses together with perceptual ones in the form of adversarial and feature discriminator loss functions. To better handle phase information the proposed method operates over the complex-valued spectrogram using two separate channels. Unlike prior work which mainly considers low and high frequency concatenation for audio super-resolution, the proposed method directly predicts the full frequency range. We demonstrate high performance across a wide range of sample rates considering both speech and music. AERO outperforms the evaluated baselines considering Log-Spectral Distance, ViSQOL, and the subjective MUSHRA test. Audio samples and code are available at https://pages.cs.huji.ac.il/adiyoss-lab/aer

Photovoltaic restoration of sight with high visual acuity

Patients with retinal degeneration lose sight due to the gradual demise of photoreceptors. Electrical stimulation of surviving retinal neurons provides an alternative route for the delivery of visual information. We demonstrate that subretinal implants with 70-μm-wide photovoltaic pixels provide highly localized stimulation of retinal neurons in rats. The electrical receptive fields recorded in retinal ganglion cells were similar in size to the natural visual receptive fields. Similarly to normal vision, the retinal response to prosthetic stimulation exhibited flicker fusion at high frequencies, adaptation to static images and nonlinear spatial summation. In rats with retinal degeneration, these photovoltaic arrays elicited retinal responses with a spatial resolution of 64 ± 11 μm, corresponding to half of the normal visual acuity in healthy rats. The ease of implantation of these wireless and modular arrays, combined with their high resolution, opens the door to the functional restoration of sight in patients blinded by retinal degeneration

Mechanisms of electrical vasoconstriction

Abstract Background Electrical vasoconstriction is a promising approach to control blood pressure or restrict bleeding in non-compressible wounds. We explore the neural and non-neural pathways of electrical vasoconstriction in-vivo. Methods Charge-balanced, asymmetric pulses were delivered through a pair of metal disc electrodes. Vasoconstriction was assessed by measuring the diameter of rat saphenous vessels stimulated with low-voltage (20 V, 1 ms) and high-voltage (150 V, 10 μs) stimuli at 10 Hz for 5 min. Activation pathways were explored by topical application of a specific neural agonist (phenylephrine, alpha-1 receptor), a non-specific agonist (KCl) and neural inhibitors (phenoxybenzamine, 25 mg/ml; guanethidine, 1 mg/ml). Acute tissue damage was assessed with a membrane permeability (live-dead) fluorescent assay. The Joule heating in tissue was estimated using COMSOL Multiphysics modeling. Results During stimulation, arteries constricted to 41 ± 8% and 37 ± 6% of their pre-stimulus diameter with low- and high-voltage stimuli, while veins constricted to 80 ± 18% and 40 ± 11%, respectively. In arteries, despite similar extent of constriction, the recovery time was very different: about 30 s for low-voltage and 10 min for high-voltage stimuli. Neural inhibitors significantly reduced low-voltage arterial constriction, but did not affect high-voltage arterial or venous constriction, indicating that high-voltage stimuli activate non-neural vasoconstriction pathways. Adrenergic pathways predominantly controlled low-voltage arterial but not venous constriction, which may involve a purinergic pathway. Viability staining confirmed that stimuli were below the electroporation threshold. Modeling indicates that heating of the blood vessels during stimulation (< 0.2 °C) is too low to cause vasoconstriction. Conclusions We demonstrate that low-voltage stimuli induce reversible vasoconstriction through neural pathways, while high-voltage stimuli activate non-neural pathways, likely in addition to neural stimulation. Different stimuli providing precise control over the extent of arterial and venous constriction as well as relaxation rate could be used to control bleeding, perfusion or blood pressure

Perceptual learning based on a temporal stimulus enhances visual function in adult amblyopic subjects

Abstract Studies have shown that Perceptual Learning (PL) can lead to enhancement of spatial visual functions in amblyopic subjects. Here we aimed to determine whether a simple flickering stimulus can be utilized in PL to enhance temporal function performance and whether enhancement will transfer to spatial functions in amblyopic subjects. Six adult amblyopic and six normally sighted subjects underwent an evaluation of their performance of baseline psychophysics spatial functions (Visual acuity (VA), contrast sensitivity (CS), temporal functions (critical fusion frequency (CFF) test), as well as a static and flickering stereopsis test, and an electrophysiological evaluation (VEP). The subjects then underwent 5 training sessions (on average, a total of 150 min over 2.5 weeks), which included a task similar to the CFF test using the method of constant stimuli. After completing the training sessions, subjects repeated the initial performance evaluation tasks. All amblyopic subjects showed improved temporal visual performance (CFF) in the amblyopic eye (on average, 17%, p << 0.01) following temporal PL. Generalization to spatial, spatio-temporal, and binocular tasks was also found: VA increased by 0.12 logMAR (p = 0.004), CS in backward masking significantly increased (by up to 19%, p = 0.003), and flickering stereopsis increased by 85 arcsec (p = 0.048). These results were further electrophysiologically manifested by an increase in VEP amplitude (by 43%, p = 0.03), increased Signal-to-Noise ratio (SNR) (by 39%, p = 0.024) to levels not different from normally sighted subjects, along with an improvement in inter-ocular delay (by 5.8 ms, p = 0.003). In contrast, no significant effect of training was found in the normally sighted group. These results highlight the potential of PL based on a temporal stimulus to improve the temporal and spatial visual performance in amblyopes. Future work is needed to optimize this method for clinical applications

Irreversible electroporation of human primary uveal melanoma in enucleated eyes.

Uveal melanoma (UM) is the most common primary intraocular tumor in adults and is characterized by high rates of metastatic disease. Although brachytherapy is the most common globe-sparing treatment option for small- and medium-sized tumors, the treatment is associated with severe adverse reactions and does not lead to increased survival rates as compared to enucleation. The use of irreversible electroporation (IRE) for tumor ablation has potential advantages in the treatment of tumors in complex organs such as the eye. Following previous theoretical work, herein we evaluate the use of IRE for uveal tumor ablation in human ex vivo eye model. Enucleated eyes of patients with uveal melanoma were treated with short electric pulses (50-100 µs, 1000-2000 V/cm) using a customized electrode design. Tumor bioimpedance was measured before and after treatment and was followed by histopathological evaluation. We found that IRE caused tumor ablation characterized by cell membrane disruption while sparing the non-cellular sclera. Membrane disruption and loss of cellular capacitance were also associated with significant reduction in total tumor impedance and loss of impedance frequency dependence. The effect was more pronounced near the pulsing electrodes and was dependent on time from treatment to fixation. Future studies should further evaluate the potential of IRE as an alternative method of uveal melanoma treatment

Hemorrhage control of liver injury by short electrical pulses.

Trauma is a leading cause of death among young individuals globally and uncontrolled hemorrhage is the leading cause of preventable death. Controlling hemorrhage from a solid organ is often very challenging in military as well as civilian setting. Recent studies demonstrated reversible vasoconstriction and irreversible thrombosis following application of microseconds-long electrical pulses. The current paper describes for the first time reduction in bleeding from the injured liver in rat and rabbit model in-vivo. We applied short (25 and 50 µs) electrical pulses of 1250 V/cm to rats and rabbit liver following induction of standardized penetrating injury and measured the amount of bleeding into the abdominal cavity one hour post injury. We found a 60 and 36 percent reduction in blood volume in rats treated by 25 µs and 50 µs, respectively (P<0.001). Similar results were found for the rabbit model. Finite element simulation revealed that the effect was likely non-thermal. Histological evaluation found local cellular injury with intravascular thrombosis. Further research should be done to fully explore the mechanism of action and the potential use of short electric pulses for hemorrhage control

Modulation of Transgene Expression in Retinal Gene Therapy by Selective Laser Treatment

PURPOSE. To develop a method for modulation of transgene expression in retinal pigment epithelium (RPE) using scanning laser that spares neurosensory retina.METHODS. Fifteen pigmented rabbits received subretinal injection of recombinant adeno-associated virus (rAAV-2) encoding green fluorescent protein (GFP). GFP expression was measured using confocal scanning laser ophthalmoscopy (cSLO) fluorescence imaging and immunohistochemistry. To reduce the total expression in RPE by half, 50% of the transfected RPE cells were selectively destroyed by microsecond exposures to scanning laser with 50% pattern density. the selectivity of RPE destruction and its migration and proliferation were monitored using fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), and light, transmission, and scanning electron microscopy. 5-Bromo-20-dioxyuridine (BrdU) assay was performed to evaluate proliferation of RPE cells.RESULTS. RPE cells were selectively destroyed by the line scanning laser with 15 mu s exposures, without damage to the photoreceptors or Bruch's membrane. RPE cells started migrating after the first day, and in 1 week there was complete restoration of RPE monolayer. Selective laser treatment decreased the GFP fluorescence by 54% as compared to control areas; this was further decreased by an additional 48% following a second treatment 1 month later. BrdU assay demonstrated proliferation in approximately half of the RPE cells in treatment areas.CONCLUSIONS. Microsecond exposures produced by scanning laser destroyed RPE cells selectively, without damage to neural retina. Continuity of RPE layer is restored within days by migration and proliferation, but transgene not integrated into the nucleus is not replicated. Therefore, gene expression can be modulated in a precise manner by controlling the laser pattern density and further adjusted using repeated applications. (Invest Ophthalmol Vis Sci. 2013;54:1873-1880) DOI:10.1167/iovs.12-10933Guillingham Pan-American FellowshipPan-American Ophthalmological FoundationRetina Research FoundationStanford Univ, Dept Ophthalmol, Stanford, CA 94305 USAStanford Univ, Hansen Expt Phys Lab, Stanford, CA 94305 USAFed Univ São Paulo UNIFESP, São Paulo, BrazilAvalanche Biotechnol Inc, San Francisco, CA USAFed Univ São Paulo UNIFESP, São Paulo, BrazilWeb of Scienc