Investigation of the stimulation capabilities of a high-resolution neurorecording probe for the application of closed-loop deep brain stimulation

Deep brain stimulation is an established surgical treatment for several neurological and movement disorders, such as Parkinson's disease, in which electrostimulation is applied to targeted deep nuclei in the basal ganglia through implanted electrode leads. Recent technological improvements in the field have focused on the theoretical advantage of current steering and adaptive (closed-loop) deep brain stimulation. Current steering between several active electrodes would allow for improved accuracy when targeting the desired brain structures. This has the additional benefit of avoiding undesired stimulation of neural tracts that are related to side effects, e.g., internal capsule fibres of passage in subthalamic nucleus deep brain stimulation. Closed-loop deep brain stimulation is based on the premise of continuous recording of a proxy for pathological neural activity (such as beta-band power of measured local field potentials in patients with Parkinson's disease) and accordingly adapting the used stimulus parameters. In this study, we investigate the suitability of an existing highresolution neurorecording probe for high-precision neurostimulation. If a subset of the probe's recording electrodes can be used for stimulation, then the probe would be a suitable candidate for closed-loop deep brain stimulation. A finiteelement model is used to calculate the electric potential, induced by current injection through the high-resolution probe, for different sets of active electrodes. Volumes of activated tissue are calculated and a comparison is made between the highresolution probe and a conventional stimulation lead. We investigate the capability of the probe to shift the volume of activated tissue by steering currents to different sets of active electrodes. Finally, safety limits for the injected current are used to determine the size of the volume in which neurons can be activated with the relatively small electrodes patches on the highresolution probe

Microscopic State of Polymer Network Chains upon Swelling and Deformation

We use low-resolution proton NMR to probe the chain deformation in swollen and nonlinearly deformed vulcanized rubber and end-linked PDMS networks on a microscopic level, extending earlier work focusing on uniaxial stretching and isotropic dilation upon swelling toward biaxial deformation and deformation of swollen samples. Previous studies have revealed that chain deformation in bulk samples is best described by tube models, and that chains in swollen samples deform affinely after an initial desinterspersion stage, upon which entanglement-related packing effects are relieved. We test whether a subsequent deformation may also be closer to affine, and find that this is not the case. Unexpectedly, nonisotropic deformation of swollen samples also follows tube-model predictions, which is explained by a dominance of structural inhomogeneities and significant reorganization of the topological constraints active in the swollen and possibly even the bulk state.Fil: Naumova, Anna. Martin Luther Universität Halle Wittenberg; AlemaniaFil: Agudelo Mora, Diana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Villar, Marcelo Armando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Ingeniería Química; ArgentinaFil: Vega, Daniel Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; ArgentinaFil: Valentin, Juan Lopez. Instituto en Ciencia y Tecnología de Polímeros; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Saalwächter, Kay. Martin Luther Universität Halle Wittenberg; Alemani

A neural probe with up to 966 electrodes and up to 384 configurable channels in 0.13 μm SOI CMOS

In vivo recording of neural action-potential and local-field-potential signals requires the use of high-resolution penetrating probes. Several international initiatives to better understand the brain are driving technology efforts towards maximizing the number of recording sites while minimizing the neural probe dimensions. We designed and fabricated (0.13-μm SOI Al CMOS) a 384-channel configurable neural probe for large-scale in vivo recording of neural signals. Up to 966 selectable active electrodes were integrated along an implantable shank (70 μm wide, 10 mm long, 20 μm thick), achieving a crosstalk of −64.4 dB. The probe base (5 × 9 mm2) implements dual-band recording and a 1

A 128-channel real-time VPDNN stimulation system for a visual cortical neuroprosthesis

With the recent progress in developing large-scale micro-electrodes, cortical neuroprotheses supporting hundreds of electrodes will be viable in the near future. We describe work in building a visual stimulation system that receives camera input images and produces stimulation patterns for driving a large set of electrodes. The system consists of a convolutional neural network FPGA accelerator and a recording and stimulation Application-Specific Integrated Circuit (ASIC) that produces the stimulation patterns. It is aimed at restoring visual perception in visually impaired subjects. The FPGA accelerator, VPDNN, runs a visual prosthesis network that generates an output used to create stimulation patterns, which are then converted by the ASIC into current pulses to drive a multi-electrode array. The accelerator exploits spatial sparsity and the use of reduced bit precision parameters for reduced computation, memory and power for portability. Experimental results from the VPDNN show that the 94.5K parameter 14-layer CNN receiving an input of 128 × 128 has an inference frame rate of 83 frames per sec (FPS) and uses only an incremental power of 0.1 W, which is at least 10× lower than that measured from a Jetson Nano. The ASIC adds a maximum delay of 2ms, however it does not impact the FPS thanks to double-buffered memory. Index Terms—Visual prosthesis, convolutional neural network, FPGA Accelerator, stimulation and recording ASI

α-FAPbI3 powder presynthesized by microwave irradiation for photovoltaic applications

The development of up-scalable and high-throughput methodologies to fabricate high-efficiency lead halide perovskite solar cells (PSCs) based on α-phase formamidinium lead iodide (FAPbI3) is one of the main challenges of making solar energy economical. In this context, PSCs based on α-phase formamidinium lead iodide (FAPbI3) are receiving special attention as this perovskite has the highest theoretical photoconversion efficiency (PCE). This manuscript reports an easy, fast and environmentally-friendly way to prepare α-FAPbI3 black powders by a microwave-assisted synthesis and their application in solar cells. The α-FAPbI3 powders consist of micrometric particles that can be stored for weeks in a closed vial at ambient conditions. This technique presents an enormous potential for upscaling FAPbI3 powders synthesis prerequisite necessary for large scale commercialization. The performance of the presynthesized FAPbI3-based solar cell was comparable with that of PSCs fabricated with the conventional procedure from precursors solutions, leading to a maximum PCE value of 18.15%, with an VOC=1.07 V, a Jsc=24.28 mA/cm2 and an FF=70%. The presynthesized FAPbI3-based solar cell was further modified through the addition of methylammonium chloride (MACl) in order to study the generality of the approach. The optical band gap for the presynthesized perovskite shifted from ∼1.43 eV to ∼1.55 eV with the MACl addition (30 mol%), indicating the formation of a mixed methylammonium and formamidinium based perovskite material (MAFAPbI3). In addition, the incorporation of MACl led to an increase in the grain size and the disappearance of the residual δ-phase perovskite, thus improving the efficiency of the final device.Funding for open access charge: CRUE-Universitat Jaume

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Rábago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Rábago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006). The funders played no role in study design, data collection, data analysis, manuscript preparation and/or publication decisions

Epigenetic loss of RNA‑methyltransferase NSUN5 in glioma targets ribosomes to drive stress adaptive translational program

Tumors have aberrant proteomes that often do not match their corresponding transcriptome profiles. One possible cause of this discrepancy is the existence of aberrant RNA modification landscapes in the so-called epitranscriptome. Here, we report that human glioma cells undergo DNA methylation-associated epigenetic silencing of NSUN5, a candidate RNA methyltransferase for 5-methylcytosine. In this setting, NSUN5 exhibits tumor-suppressor characteristics in vivo glioma models. We also found that NSUN5 loss generates an unmethylated status at the C3782 position of 28S rRNA that drives an overall depletion of protein synthesis, and leads to the emergence of an adaptive translational program for survival under conditions of cellular stress. Interestingly, NSUN5 epigenetic inactivation also renders these gliomas sensitive to bioactivatable substrates of the stress-related enzyme NQO1. Most importantly, NSUN5 epigenetic inactivation is a hallmark of glioma patients with long-term survival for this otherwise devastating disease