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PURPOSE: This study aims to explore the feasibility and performance of three-dimensional ultrasound (3DUS) imaging in ophthalmology using commercially available ultrasound probes adapted to a slit lamp. SIGNIFICANCE: Despite ultrasounds long-standing application in eye care for visualizing ocular components, the evolution of 3DUS technology has remained inactive, with limited development and commercial availability. This study introduces a novel method that could potentially enhance ophthalmic diagnostics and treatment planning by providing comprehensive 3D views of ocular structures using existing ultrasound probes adapted to the conventional slit lamp. METHODS: A custom system was designed for mounting a linear actuator to a slit lamp and enabling the horizontal actuation of any ultrasound probe. Ophthalmic and non-ophthalmic ultrasound probes were tested for their ability to reconstruct 3DUS images of the posterior pole. The study involved designing and evaluating three US phantoms ex vivo and performing in vivo imaging on human subjects to assess the systems applicability. RESULTS: The system successfully acquired 3D volume scans of phantoms and live human eyes, demonstrating the systems potential for detailed ocular imaging. The adaptability of the device allowed for compatibility with various ultrasound probes. In vivo imaging revealed the systems capability to produce high-resolution 3D reconstructions of ocular structures, including eyes with pathological conditions. CONCLUSIONS: The introduction of a slit lamp-mounted 3DUS system represents a significant advancement in ophthalmic ultrasonography, offering a practical and accessible solution for comprehensive 3D ocular assessments. The devices modularity and compatibility with existing ultrasound probes make it a versatile tool for a wide range of ophthalmic applications. Further research and clinical trials are needed to optimize the systems performance and validate its clinical utility.

Spindle-shaped waves of oscillations emerge in EEG scalp recordings during human and rodent non-REM sleep. The association of these 10-16 Hz oscillations with events during prior wakefulness suggests a role in memory consolidation. Human and rodent depth electrodes in the brain record strong spindles throughout the cortex and hippocampus, with possible origins in the thalamus. However, the source and targets of the spindle oscillations from the hippocampus are unclear. Here, we employed an in vitro reconstruction of four subregions of the hippocampal formation with separate microfluidic tunnels for single axon communication between subregions assembled on top of a microelectrode array. We recorded spontaneous 400-1000 ms long spindle waves at 10-16 Hz in single axons passing between subregions as well as from individual neurons in those subregions. Spindles were nested within slow waves. The highest amplitudes and most frequent occurrence suggest origins in CA3 neurons that send feed-forward axons into CA1 and feedback axons into DG. Spindles had 50-70% slower conduction velocities than spikes and were not phase-locked to spikes suggesting that spindle mechanisms are independent of action potentials. Therefore, consolidation of declarative-cognitive memories in the hippocampus may be separate from the more easily accessible consolidation of memories related to thalamic motor function.

In this report, we investigate the use of a radio drama competition to boost motivation, self-confidence, and cooperation in language learning for primary and secondary school students in Hong Kong. The results suggest the radio drama competition had a positive impact on increasing motivation, collaboration, and confidence in language learning. For the study, we used online surveys and interviews with students and teachers who participated in the radio drama competition to examine their perceptions of the competition. We have included the surveys and interview results of two competitions in consecutive years, and both years' results indicate students had positive views about their experience. Both students and teachers believed the competition enhanced collaboration and teamwork, confidence, and communication skills most. This paper contributes to the literature by shedding light on the pedagogical implications of English teachers incorporating more radio drama and language arts into their classrooms to improve students' language learning. Well-selected language arts materials could increase students' language learning process as well as their motivation and self-confidence to learn the target language.

[This corrects the article DOI: 10.3389/fdata.2022.787421.].

The sub-regions of the hippocampal formation are essential for episodic learning and memory formation, yet the spike dynamics of each region contributing to this function are poorly understood, in part because of a lack of access to the inter-regional communicating axons. Here, we reconstructed hippocampal networks confined to four subcompartments in 2D cultures on a multi-electrode array that monitors individual communicating axons. In our novel device, somal, and axonal activity was measured simultaneously with the ability to ascertain the direction and speed of information transmission. Each sub-region and inter-regional axons had unique power-law spiking dynamics, indicating differences in computational functions, with abundant axonal feedback. After stimulation, spiking, and burst rates decreased in all sub-regions, spikes per burst generally decreased, intraburst spike rates increased, and burst duration decreased, which were specific for each sub-region. These changes in spiking dynamics post-stimulation were found to occupy a narrow range, consistent with the maintenance of the network at a critical state. Functional connections between the sub-region neurons and communicating axons in our device revealed homeostatic network routing strategies post-stimulation in which spontaneous feedback activity was selectively decreased and balanced by decreased feed-forward activity. Post-stimulation, the number of functional connections per array decreased, but the reliability of those connections increased. The networks maintained a balance in spiking and bursting dynamics in response to stimulation and sharpened network routing. These plastic characteristics of the network revealed the dynamic architecture of hippocampal computations in response to stimulation by selective routing on a spatiotemporal scale in single axons.

Acute myeloid leukemia (AML) is a heterogeneous and deadly disease characterized by uncontrolled expansion of malignant blasts. Altered metabolism and dysregulated microRNA (miRNA) expression profiles are both characteristic of AML. However, there is a paucity of studies exploring how changes in the metabolic state of the leukemic cells regulate miRNA expression leading to altered cellular behavior. Here, we blocked pyruvate entry into mitochondria by deleting the Mitochondria Pyruvate Carrier (MPC1) gene in human AML cell lines, which decreased Oxidative Phosphorylation (OXPHOS). This metabolic shift also led to increased expression of miR-1 in the human AML cell lines tested. AML patient sample datasets showed that higher miR-1 expression correlates with reduced survival. Transcriptional and metabolic profiling of miR-1 overexpressing AML cells revealed that miR-1 increased OXPHOS, along with key metabolites that fuel the TCA cycle such as glutamine and fumaric acid. Inhibition of glutaminolysis decreased OXPHOS in miR-1 overexpressing MV4-11 cells, highlighting that miR-1 promotes OXPHOS through glutaminolysis. Finally, overexpression of miR-1 in AML cells exacerbated disease in a mouse xenograft model. Together, our work expands current knowledge within the field by uncovering novel connections between AML cell metabolism and miRNA expression that facilitates disease progression. Further, our work points to miR-1 as a potential new therapeutic target that may be used to disrupt AML cell metabolism and thus pathogenesis in the clinic.

Retinal degeneration (RD) is a significant cause of incurable blindness worldwide. Photoreceptors and retinal pigmented epithelium are irreversibly damaged in advanced RD. Functional replacement of photoreceptors and/or retinal pigmented epithelium cells is a promising approach to restoring vision. This paper reviews the current status and explores future prospects of the transplantation therapy provided by pluripotent stem cell-derived retinal organoids (ROs). This review summarizes the status of rodent RD disease models and discusses RO culture and analytical tools to evaluate RO quality and function. Finally, we review and discuss the studies in which RO-derived cells or sheets were transplanted. In conclusion, methods to derive ROs from pluripotent stem cells have significantly improved and become more efficient in recent years. Meanwhile, more novel technologies are applied to characterize and validate RO quality. However, opportunity remains to optimize tissue differentiation protocols and achieve better RO reproducibility. In order to screen high-quality ROs for downstream applications, approaches such as noninvasive and label-free imaging and electrophysiological functional testing are promising and worth further investigation. Lastly, transplanted RO-derived tissues have allowed improvements in visual function in several RD models, showing promises for clinical applications in the future.

In this community review report, we discuss applications and techniques for fast machine learning (ML) in science-the concept of integrating powerful ML methods into the real-time experimental data processing loop to accelerate scientific discovery. The material for the report builds on two workshops held by the Fast ML for Science community and covers three main areas: applications for fast ML across a number of scientific domains; techniques for training and implementing performant and resource-efficient ML algorithms; and computing architectures, platforms, and technologies for deploying these algorithms. We also present overlapping challenges across the multiple scientific domains where common solutions can be found. This community report is intended to give plenty of examples and inspiration for scientific discovery through integrated and accelerated ML solutions. This is followed by a high-level overview and organization of technical advances, including an abundance of pointers to source material, which can enable these breakthroughs.

PurposeTwo-photon excitation fluorescence (2PEF) reveals information about tissue function. Concerns for phototoxicity demand lower light exposure during imaging. Reducing excitation light reduces the quality of the image by limiting fluorescence emission. We applied deep learning (DL) super-resolution techniques to images acquired from low light exposure to yield high-resolution images of retinal and skin tissues.MethodsWe analyzed two methods: a method based on U-Net and a patch-based regression method using paired images of skin (550) and retina (1200), each with low- and high-resolution paired images. The retina dataset was acquired at low and high laser powers from retinal organoids, and the skin dataset was obtained from averaging 7 to 15 frames or 70 frames. Mean squared error (MSE) and the structural similarity index measure (SSIM) were outcome measures for DL algorithm performance.ResultsFor the skin dataset, the patches method achieved a lower MSE (3.768) compared with U-Net (4.032) and a high SSIM (0.824) compared with U-Net (0.783). For the retinal dataset, the patches method achieved an average MSE of 27,611 compared with 146,855 for the U-Net method and an average SSIM of 0.636 compared with 0.607 for the U-Net method. The patches method was slower (303 seconds) than the U-Net method (

Retinal degeneration is a leading cause of vision impairment and blindness worldwide and medical care for advanced disease does not exist. Stem cell-derived retinal organoids (RtOgs) became an emerging tool for tissue replacement therapy. However, existing RtOg production methods are highly heterogeneous. Controlled and predictable methodology and tools are needed to standardize RtOg production and maintenance. In this study, we designed a shear stress-free micro-millifluidic bioreactor for nearly labor-free retinal organoid maintenance. We used a stereolithography (SLA) 3D printer to fabricate a mold from which Polydimethylsiloxane (PDMS) was cast. We optimized the chip design using in silico simulations and in vitro evaluation to optimize mass transfer efficiency and concentration uniformity in each culture chamber. We successfully cultured RtOgs at three different differentiation stages (day 41, 88, and 128) on an optimized bioreactor chip for more than 1 month. We used different quantitative and qualitative techniques to fully characterize the RtOgs produced by static dish culture and bioreactor culture methods. By analyzing the results from phase contrast microscopy, single-cell RNA sequencing (scRNA seq), quantitative polymerase chain reaction (qPCR), immunohistology, and electron microscopy, we found that bioreactor-cultured RtOgs developed cell types and morphology comparable to static cultured ones and exhibited similar retinal genes expression levels. We also evaluated the metabolic activity of RtOgs in both groups using fluorescence lifetime imaging (FLIM), and found that the outer surface region of bioreactor cultured RtOgs had a comparable free/bound NADH ratio and overall lower long lifetime species (LLS) ratio than static cultured RtOgs during imaging. To summarize, we validated an automated micro-millifluidic device with significantly reduced shear stress to produce RtOgs of comparable quality to those maintained in conventional static culture.

A systematic experimental study of viscous air damping in laterally moving planar microstructures is reported. Previous studies indicated that Couette and Stokes flow models underestimate microstructural damping. To investigate this discrepancy, a series of lateral resonant microstructures with different damping plates and combs was fabricated by polysilicon surface micromachining. The resonant frequencies and quality factors of the structures were measured electrically. By analyzing these data, the damping effects due to different geometries were elucidated and compared to theory. The results indicated that if edge and finite-size effects are included in the model, reasonably accurate predictions of the quality factors can be obtained even for small geometries and comb drives. An empirical formula that predicts the quality factor for a range of plate sizes and comb designs was derived. The damping effects as functions of structural thickness and structure-to-substrate separation are also reported.

An accurate sky polarization field map is a prerequisite for polarization navigation applications. In this article, a detector or sky full-polarization imaging detection is described, the major error-influencing factors (MEIFS) are obtained, and the error propagation is modeled and analyzed. We reveal the relationship between the error of the inversed Stokes vector and the condition number of the detector matrix, which shows that the error of the inversed Stokes vector is affected by the Stokes vector of the incident light itself and the MEIFS together, with the MEIFS playing a decisive role. With the MEIFS optimized, the impact of detector error on the inversed Stokes vector is attenuated. A control equation for system calibration is also deduced which can establish the connection between the detector matrix design and calibration process. The work in this article provides a reference for optimization and calibration of sky full-polarization imaging detectors.

The tri-synaptic pathway in the mammalian hippocampus enables cognitive learning and memory. Despite decades of reports on anatomy and physiology, the functional architecture of the hippocampal network remains poorly understood in terms of the dynamics of axonal information transfer between subregions. Information inputs largely flow from the entorhinal cortex (EC) to the dentate gyrus (DG), and then are processed further in the CA3 and CA1 before returning to the EC. Here, we reconstructed elements of the rat hippocampus in a novel device over an electrode array that allowed for monitoring the directionality of individual axons between the subregions. The direction of spike propagation was determined by the transmission delay of the axons recorded between two electrodes in microfluidic tunnels. The majority of axons from the EC to the DG operated in the feed-forward direction, with other regions developing unexpectedly large proportions of feedback axons to balance excitation. Spike timing in axons between each region followed single exponential log-log distributions over two orders of magnitude from 0.01 to 1 s, indicating that conventional descriptors of mean firing rates are misleading assumptions. Most of the spiking occurred in bursts that required two exponentials to fit the distribution of inter-burst intervals. This suggested the presence of up-states and down-states in every region, with the least up-states in the DG to CA3 feed-forward axons and the CA3 subregion. The peaks of the log-normal distributions of intra-burst spike rates were similar in axons between regions with modes around 95 Hz distributed over an order of magnitude. Burst durations were also log-normally distributed around a peak of 88 ms over two orders of magnitude. Despite the diversity of these spike distributions, spike rates from individual axons were often linearly correlated to subregions. These linear relationships enabled the generation of structural connectivity graphs, not possible previously without the directional flow of axonal information. The rich axonal spike dynamics between subregions of the hippocampus reveal both constraints and broad emergent dynamics of hippocampal architecture. Knowledge of this network architecture may enable more efficient computational artificial intelligence (AI) networks, neuromorphic hardware, and stimulation and decoding from cognitive implants.

Pluripotent stem cell-derived organoid technologies have opened avenues to preclinical basic science research, drug discovery, and transplantation therapy in organ systems. Stem cell-derived organoids follow a time course similar to species-specific organ gestation in vivo. However, heterogeneous tissue yields, and subjective tissue selection reduce the repeatability of organoid-based scientific experiments and clinical studies. To improve the quality control of organoids, we introduced a live imaging technique based on two-photon microscopy to non-invasively monitor and characterize retinal organoids' (RtOgs') long-term development. Fluorescence lifetime imaging microscopy (FLIM) was used to monitor the metabolic trajectory, and hyperspectral imaging was applied to characterize structural and molecular changes. We further validated the live imaging experimental results with endpoint biological tests, including quantitative polymerase chain reaction (qPCR), single-cell RNA sequencing, and immunohistochemistry. With FLIM results, we analyzed the free/bound nicotinamide adenine dinucleotide (f/b NADH) ratio of the imaged regions and found that there was a metabolic shift from glycolysis to oxidative phosphorylation. This shift occurred between the second and third months of differentiation. The total metabolic activity shifted slightly back toward glycolysis between the third and fourth months and stayed relatively stable between the fourth and sixth months. Consistency in organoid development among cell lines and production lots was examined. Molecular analysis showed that retinal progenitor genes were expressed in all groups between days 51 and 159. Photoreceptor gene expression emerged around the second month of differentiation, which corresponded to the shift in the f/b NADH ratio. RtOgs between 3 and 6 months of differentiation exhibited photoreceptor gene expression levels that were between the native human fetal and adult retina gene expression levels. The occurrence of cone opsin expression (OPN1 SW and OPN1 LW) indicated the maturation of photoreceptors in the fourth month of differentiation, which was consistent with the stabilized level of f/b NADH ratio starting from 4 months. Endpoint single-cell RNA and immunohistology data showed that the cellular compositions and lamination of RtOgs at different developmental stages followed those in vivo.

BackgroundMusic therapy improves neuronal activity and connectivity of healthy persons and patients with clinical symptoms of neurological diseases like Parkinson's disease, Alzheimer's disease, and major depression. Despite the plethora of publications that have reported the positive effects of music interventions, little is known about how music improves neuronal activity and connectivity in afflicted patients.MethodsFor patients suffering from Parkinson's disease (PD), we propose a daily 25-min music-based synchronous finger tapping (SFT) intervention for 8 weeks. Eligible participants with PD are split into two groups: an intervention group and a control arm. In addition, a third cohort of healthy controls will be recruited. Assessment of finger tapping performances, the Unified Parkinson's Disease Rating Scale (UPDRS), an n-back test, the Montreal Cognitive Assessment (MoCA), as well as oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (HbR), and total hemoglobin activation collected by functional near-infrared spectroscopy (fNIRS) are measured at baseline, week 4 (during), week 8 (post), and week 12 (retention) of the study. Data collected from the two PD groups are compared to baseline performances from healthy controls.DiscussionThis exploratory prospective trial study investigates the cortical neuronal activity and therapeutic effects associated with an auditory external cue used to induce automatic and implicit synchronous finger tapping in patients diagnosed with PD. The extent to which the intervention is effective may be dependent on the severity of the disease. The study's findings are used to inform larger clinical studies for optimization and further exploration of the therapeutic effects of movement-based music therapy on neural activity in neurological diseases.Trial registrationClinicalTrials.gov NCT04212897 . Registered on December 30, 2019. The participant recruitment and study protocol have received ethical approval from the First Affiliated Hospital of Dalian Medical University. The hospital Protocol Record number is PJ-KY-2019-123. The protocol was named "fNIRS Studies of Music Intervention of Parkinson's Disease." The current protocol is version 1.1, revised on September 1, 2020.

Machining surface topography is a key factor affecting the properties of optical materials.It is generally accepted that the fracture mode tends to dominate practical concerns onmachined parts and the elastic recovery area decreases with the increase of normal load.However, material removal rate is low for ductile zone processing of brittle materials. In thiscase, pile-up and elastic recovery are key factors for surface quality. In this study, an accuratescratching and ploughing hardness model with consideration of both pile-up and elasticrecovery was established based on a series of continuous and constant nanoscratch tests.The hardness evolution mechanism under different nanoscratch deformation modes wasthen investigated. It was found that, in different modes, hardness values exhibited differentcharacteristics due to the change of elastic recovery rate and the intersection of elastic andplastic states. Further, the mapping relationship between hardness dispersion and surfacemorphology characteristics was also investigated. The results indicated that high degree ofhardness dispersion usually corresponded to modes I and II while stable hardness valuerepresented a steady plastic stage. Based on the intrinsic relationship between evolution ofhardness and deformation modes, predicting hardness distribution by in-situ testing dataand then adjusting deformation mode in real time would be helpful in optimizing surfacequality.

Metabolic pathways regulate T cell development and function, but many remain understudied. Recently, the mitochondrial pyruvate carrier (MPC) was identified as the transporter that mediates pyruvate entry into mitochondria, promoting pyruvate oxidation. Here we find that deleting Mpc1, an obligate MPC subunit, in the hematopoietic system results in a specific reduction in peripheral αβ T cell numbers. MPC1-deficient T cells have defective thymic development at the β-selection, intermediate single positive (ISP)-to-double-positive (DP), and positive selection steps. We find that early thymocytes deficient in MPC1 display alterations to multiple pathways involved in T cell development. This results in preferred escape of more activated T cells. Finally, mice with hematopoietic deletion of Mpc1 are more susceptible to experimental autoimmune encephalomyelitis. Altogether, our study demonstrates that pyruvate oxidation by T cell precursors is necessary for optimal αβ T cell development and that its deficiency results in reduced but activated peripheral T cell populations.

An integrated centrifugal microfluidic device was developed to preconcentrate and detect hazardous mercury (II) in water with ionic liquid as environmentally friendly extractant. An automatically salt-controlled ionic liquid dispersive liquid-liquid microextraction on a centrifugal microfluidic device was designed, fabricated, and characterized. The entire liquid transport mixing and separation process was controlled by rotation speed, siphon valves, and capillary valves. Still frame images on the rotating device showed the process in detail, revealing the sequential steps of mixing, siphon priming, transportation between chambers, and phase separation. The preconcentration of red dye could be clearly observed with the naked eye. By combining fluorescence probe and microscopy techniques, the device was tested to determine ppb-level mercury (II) in water, and was found to exhibit good linearity and low detection limit.

Significant efforts have been devoted to developing trace-level quantification of Hg2+. In this work, a novel fluorescence detection (FD) approach combined with preconcentration of Hg2+ in ionic liquid (IL), N-octylpyridinium tetrafluoroborate ([OPy]+[BF4]-), was developed for the determination of trace Hg2+ in water. The temperature-controlled ionic liquid dispersive liquid-liquid microextraction (TC-IL-DLLME) technique was used to improve the enrichment factor. After extraction and centrifugal separation, precipitated IL was diluted with water and acetonitrile containing the fluorescent probe. Under optimum conditions, the photoluminescence intensity of the fluorescence emission peak was found to be linear with the concentration of Hg2+ in the range from 0.1 to 0.5 μg L-1. The limit of detection for the TC-IL-DLLME-FD method was calculated to be 0.0342 μg L-1 (S/N = 3). Further, the selectivity of the sensor was measured by evaluating its response to other heavy-metal ions and was shown to be excellent. Recoveries were assessed by spiking water samples with different Hg2+ standard stock solutions, giving satisfactory recoveries from 80 to 110%.

The gyrokinetic toroidal code at Princeton (GTC-P) is a highly scalable and portable particle-in-cell (PIC) code. It solves the 5-D Vlasov–Poisson equation featuring efficient utilization of modern parallel computer architectures at the petascale and beyond. Motivated by the goal of developing a modern code capable of dealing with the physics challenge of increasing problem size with sufficient resolution, new thread-level optimizations have been introduced as well as a key additional domain decomposition. GTC-P’s multiple levels of parallelism, including internode 2-D domain decomposition and particle decomposition, as well as intranode shared memory partition and vectorization, have enabled pushing the scalability of the PIC method to extreme computational scales. In this article, we describe the methods developed to build a highly parallelized PIC code across a broad range of supercomputer designs. This particularly includes implementations on heterogeneous systems using NVIDIA GPU accelerators and Intel Xeon Phi (MIC) coprocessors and performance comparisons with state-of-the-art homogeneous HPC systems such as Blue Gene/Q. New discovery science capabilities in the magnetic fusion energy application domain are enabled, including investigations of ion–temperature–gradient driven turbulence simulations with unprecedented spatial resolution and long temporal duration. Performance studies with realistic fusion experimental parameters are carried out on multiple supercomputing systems spanning a wide range of cache capacities, cache-sharing configurations, memory bandwidth, interconnects, and network topologies. These performance comparisons using a realistic discovery-science-capable domain application code provide valuable insights on optimization techniques across one of the broadest sets of current high-end computing platforms worldwide.

An integrated centrifugal microfluidic device was developed to preconcentrate and detect hazardous mercury (II) in water with ionic liquid as environmentally friendly extractant. An automatically salt-controlled ionic liquid dispersive liquid-liquid microextraction on a centrifugal microfluidic device was designed, fabricated, and characterized. The entire liquid transport mixing and separation process was controlled by rotation speed, siphon valves, and capillary valves. Still frame images on the rotating device showed the process in detail, revealing the sequential steps of mixing, siphon priming, transportation between chambers, and phase separation. The preconcentration of red dye could be clearly observed with the naked eye. By combining fluorescence probe and microscopy techniques, the device was tested to determine ppb-level mercury (II) in water, and was found to exhibit good linearity and low detection limit.

In this paper, we report a new type of electrospinning collector that allows simultaneous collection and alignment of multiple poly(vinylidene fluoride-trifluoroethylene) piezoelectric fiber bundles with a controlled separation. The key enabling feature is the serrated teeth along the edges across an inclined gap as a part of the conductive collector. As a result, the electrical field across the gap is shaped to direct the electrospun fibers to merge into multiple bundles. The sharp points on the serrated teeth provide favorable charge dissipation points and thus fibers are preferentially formed bridging two closest sharp points across the gap. To investigate the effectiveness of serrated teeth on the formation of multiple fiber bundles, three-dimensional finite element simulations are conducted. The corresponding collectors are implemented to experimentally study the resulting electrospun fibers. Both simulation and experimental results suggest that multiple fiber bundles can be formed under the condition of a low teeth pitch to gap distance ratio. Furthermore, a sharper tooth angle results in a higher preferential formation of fiber bundles. Finally, the total electrospinning time should be less than 60 seconds to maintain favorable electric field profile. We also demonstrate that these piezoelectric fiber bundles can serve as ultra-flexible textile sensors.

Objectives/hypothesisPermanent facial nerve injury is a difficult challenge for both patients and physicians given its potential for debilitating functional, cosmetic, and psychological sequelae. Although current surgical interventions have provided considerable advancements in facial nerve rehabilitation, they often fail to fully address all impairments. We aim to introduce an alternative approach to facial nerve rehabilitation.Study designAcute experiments in animals with normal facial function.MethodsThe study included three anesthetized cats. Four facial muscles (levator auris longus, orbicularis oculi, nasalis, and orbicularis oris) were monitored with a standard electromyographic (EMG) facial nerve monitoring system with needle electrodes. The main trunk of the facial nerve was exposed, and a 16-channel penetrating electrode array was placed into the nerve. Electrical current pulses were delivered to each stimulating electrode individually. Elicited EMG voltage outputs were recorded for each muscle.ResultsStimulation through individual channels selectively activated restricted nerve populations, resulting in selective contraction of individual muscles. Increasing stimulation current levels resulted in increasing EMG voltage responses. Typically, selective activation of two or more distinct muscles was successfully achieved via a single placement of the multi-channel electrode array by selection of appropriate stimulation channels.ConclusionWe have established in the animal model the ability of a penetrating electrode array to selectively stimulate restricted fiber populations within the facial nerve and to selectively elicit contractions in specific muscles and regions of the face. These results show promise for the development of a facial nerve implant system.Level of evidenceN/A.Laryngoscope, 2016 127:460-465, 2017.

In this paper, we describe a novel and simple process for the fabrication of all-transparent and encapsulated polymeric nanofluidic devices using nano-indentation lithography. First, a nanomechanical probe is used to 'scratch' nanoscale channels on polymethylmethacrylate (PMMA) substrates with sufficiently high hardness. Next, polydimethylsiloxane (PDMS) is used twice to duplicate the nanochannels onto PDMS substrates from the 'nano-scratched' PMMA substrates. A number of experiments are conducted to explore the relationships between the nano-indentation parameters and the nanochannel dimensions and to control the aspect ratio of the fabricated nanochannels. In addition, traditional photolithography combined with soft lithography is employed to fabricate microchannels on another PDMS 'cap' substrate. After manually aligning the substrates, all uncovered channels on two separate PDMS substrates are bonded to achieve a sealed and transparent nanofluidic device, which makes the dimensional transition from microscale to nanoscale feasible. The smallest dimensions of the achievable nanochannels that we have demonstrated thus far are of ~20 nm depth and ~800 nm width, with lengths extendable beyond 100 μm. Fluid flow experiments are performed to verify the reliability of the device. Two types of colloidal solution are used to visualize the fluid flow through the nanochannels, that is, ethanol is mixed with gold colloid or fluorescent dye (fluorescein isothiocyanate), and the flow rate and filling time of liquid in the nanochannels are estimated based on time-lapsed image data. The simplicity of the fabrication process, bio-compatibility of the polymer substrates, and optical transparency of the nanochannels for flow visualization are key characteristics of this approach that will be very useful for nanofluidic and biomolecular research applications in the future.