Optogenetic Stimulation Using Anion Channelrhodopsin (GtACR1) Facilitates Termination of Reentrant Arrhythmias With Low Light Energy Requirements: A Computational Study

Optogenetic defibrillation of hearts expressing light-sensitive cation channels (e.g., ChR2) has been proposed as an alternative to conventional electrotherapy. Past modeling work has shown that ChR2 stimulation can depolarize enough myocardium to interrupt arrhythmia, but its efficacy is limited by light attenuation and high energy needs. These shortcomings may be mitigated by using new optogenetic proteins like Guillardia theta Anion Channelrhodopsin (GtACR1), which produces a repolarizing outward current upon illumination. Accordingly, we designed a study to assess the feasibility of GtACR1-based optogenetic arrhythmia termination in human hearts. We conducted electrophysiological simulations in MRI-based atrial or ventricular models (n = 3 each), with pathological remodeling from atrial fibrillation or ischemic cardiomyopathy, respectively. We simulated light sensitization via viral gene delivery of three different opsins (ChR2, red-shifted ChR2, GtACR1) and uniform endocardial illumination at the appropriate wavelengths (blue, red, or green light, respectively). To analyze consistency of arrhythmia termination, we varied pulse timing (three evenly spaced intervals spanning the reentrant cycle) and intensity (atrial: 0.001–1 mW/mm2; ventricular: 0.001–10 mW/mm2). In atrial models, GtACR1 stimulation with 0.005 mW/mm2 green light consistently terminated reentry; this was 10–100x weaker than the threshold levels for ChR2-mediated defibrillation. In ventricular models, defibrillation was observed in 2/3 models for GtACR1 stimulation at 0.005 mW/mm2 (100–200x weaker than ChR2 cases). In the third ventricular model, defibrillation failed in nearly all cases, suggesting that attenuation issues and patient-specific organ/scar geometry may thwart termination in some cases. Across all models, the mechanism of GtACR1-mediated defibrillation was voltage forcing of illuminated tissue toward the modeled channel reversal potential of −40 mV, which made propagation through affected regions impossible. Thus, our findings suggest GtACR1-based optogenetic defibrillation of the human heart may be feasible with ≈2–3 orders of magnitude less energy than ChR2.

Memristor Circuits for Simulating Neuron Spiking and Burst Phenomena

Since the introduction of memristors, it has been widely recognized that they can be successfully employed as synapses in neuromorphic circuits. This paper focuses on showing that memristor circuits can be also used for mimicking some features of the dynamics exhibited by neurons in response to an external stimulus. The proposed approach relies on exploiting multistability of memristor circuits, i.e., the coexistence of infinitely many attractors, and employing a suitable pulse-programmed input for switching among the different attractors. Specifically, it is first shown that a circuit composed of a resistor, an inductor, a capacitor and an ideal charge-controlled memristor displays infinitely many stable equilibrium points and limit cycles, each one pertaining to a planar invariant manifold. Moreover, each limit cycle is approximated via a first-order periodic approximation analytically obtained via the Describing Function (DF) method, a well-known technique in the Harmonic Balance (HB) context. Then, it is shown that the memristor charge is capable to mimic some simplified models of the neuron response when an external independent pulse-programmed current source is introduced in the circuit. The memristor charge behavior is generated via the concatenation of convergent and oscillatory behaviors which are obtained by switching between equilibrium points and limit cycles via a properly designed pulse timing of the current source. The design procedure takes also into account some relationships between the pulse features and the circuit parameters which are derived exploiting the analytic approximation of the limit cycles obtained via the DF method.

Speeds of Sound in Methanol at Temperatures from 233.33 to 353.21 K at Pressures up to 20 MPa

We report experimental speeds of sound in methanol. Measurements were conducted at temperatures from 233 to 353 K with pressures up to 20 MPa using the double-path length pulse-echo technique. The relative expanded combined uncertainty (k = 2) in measurement was estimated to vary from 0.012 to 0.014%, considering contributions from temperature, pressure, path length calibration, pulse timing, and purity of the sample. Experimental speeds of sound gained in the scope of this work were compared with the equation of state by de Reuck and Craven, as well as with further data from literature.

Dispersive-wave induced noise limits in miniature soliton microwave sources

Compact, low-noise microwave sources are required throughout a wide range of application areas including frequency metrology, wireless-communications and airborne radar systems. And the photonic generation of microwaves using soliton microcombs offers a path towards integrated, low noise microwave signal sources. In these devices, a so called quiet-point of operation has been shown to reduce microwave frequency noise. Such operation decouples pump frequency noise from the soliton’s motion by balancing the Raman self-frequency shift with dispersive-wave recoil. Here, we explore the limit of this noise suppression approach and reveal a fundamental noise mechanism associated with fluctuations of the dispersive wave frequency. At the same time, pump noise reduction by as much as 36 dB is demonstrated. This fundamental noise mechanism is expected to impact microwave noise (and pulse timing jitter) whenever solitons radiate into dispersive waves belonging to different spatial mode families.

Development of Prototype Simplified Neutron Scatter Camera for Nuclear Safeguards Applications

Neutron scatter cameras are a type of directional neutron detectors that rely on multiple neutron scatters to generate images that can reveal the direction and distribution of neutron sources. Fast neutron cameras which have recently been developed rely on multiple detector volumes and make use of neutron time-of-flight measurements. These designs, though effective in localizing the source direction, relies on a large amount of detection and electrical equipment, thus increasing size, cost, and complexity of the systems to unreasonable levels for some applications. This project seeks to develop a compact scatter camera that is less expensive than systems relying on multiple detector volumes. Crucially, two components and capabilities are needed to achieve this: fast scintillation detection materials and picosecond electrical pulse timing. Utilizing such electronics, distinguishing between scintillation light pulses generated by the same neutron within one detector volume is possible. An MCNPX-PoliMi model of such a system has been developed to guide prototype designs. A cube of EJ-230 fast plastic scintillator and six photomultiplier tubes (PMTs) were used to construct the prototype camera that localizes neutron sources based on the principle of cone back projection. Prototypes of the system in one, two, and three dimensions have shown promising initial results when coupled with a script that algorithmically identifies candidate neutron double scatter events and back projects probability cones in the direction of possible sources. Imaging resolution/quality, double scatter efficiency, and cost for the system are quantified. Paths forward for further improvement of a future system based on this camera’ operating principles are discussed.

Transmission of Binaural Cues by Bilateral Cochlear Implants: Examining the Impacts of Bilaterally Independent Spectral Peak-Picking, Pulse Timing, and Compression

Acoustic hearing listeners use binaural cues—interaural time differences (ITDs) and interaural level differences (ILDs)—for localization and segregation of sound sources in the horizontal plane. Cochlear implant users now often receive two implants (bilateral cochlear implants [BiCIs]) rather than one, with the goal to provide access to these cues. However, BiCI listeners often experience difficulty with binaural tasks. Most BiCIs use independent sound processors at each ear; it has often been suggested that such independence may degrade the transmission of binaural cues, particularly ITDs. Here, we report empirical measurements of binaural cue transmission via BiCIs implementing a common “ n-of- m” spectral peak-picking stimulation strategy. Measurements were completed for speech and nonspeech stimuli presented to an acoustic manikin “fitted” with BiCI sound processors. Electric outputs from the BiCIs and acoustic outputs from the manikin’s in-ear microphones were recorded simultaneously, enabling comparison of electric and acoustic binaural cues. For source locations away from the midline, BiCI binaural cues, particularly envelope ITD cues, were found to be degraded by asymmetric spectral peak-picking. In addition, pulse amplitude saturation due to nonlinear level mapping yielded smaller ILDs at higher presentation levels. Finally, while individual pulses conveyed a spurious “drifting” ITD, consistent with independent left and right processor clocks, such variation was not evident in transmitted envelope ITDs. Results point to avenues for improvement of BiCI technology and may prove useful in the interpretation of BiCI spatial hearing outcomes reported in prior and future studies.