To enable sophisticated optogenetic manipulation of neural circuits throughout the nervous system with limited disruption of animal behavior, light-delivery systems beyond fiber optic tethering and large, head-mounted wireless receivers are desirable. We report the development of an easy-to-construct, implantable wireless optogenetic device. Our smallest version (20 mg, 10 mm3) is two orders of magnitude smaller than previously reported wireless optogenetic systems, allowing the entire device to be implanted subcutaneously. With a radio-frequency (RF) power source and controller, this implant produces sufficient light power for optogenetic stimulation with minimal tissue heating (<1 °C). We show how three adaptations of the implant allow for untethered optogenetic control throughout the nervous system (brain, spinal cord and peripheral nerve endings) of behaving mice. This technology opens the door for optogenetic experiments in which animals are able to behave naturally with optogenetic manipulation of both central and peripheral targets.

The ability to implant electronic systems in the human body has led to many medical advances. Progress in semiconductor technology paved the way for devices at the scale of a millimeter or less ("microimplants"), but the miniaturization of the power source remains challenging. Although wireless powering has been demonstrated, energy transfer beyond superficial depths in tissue has so far been limited by large coils (at least a centimeter in diameter) unsuitable for a microimplant. Here, we show that this limitation can be overcome by a method, termed midfield powering, to create a high-energy density region deep in tissue inside of which the power-harvesting structure can be made extremely small. Unlike conventional near-field (inductively coupled) coils, for which coupling is limited by exponential field decay, a patterned metal plate is used to induce spatially confined and adaptive energy transport through propagating modes in tissue. We use this method to power a microimplant (2 mm, 70 mg) capable of closed-chest wireless control of the heart that is orders of magnitude smaller than conventional pacemakers. With exposure levels below human safety thresholds, milliwatt levels of power can be transferred to a deep-tissue (>5 cm) microimplant for both complex electronic function and physiological stimulation. The approach developed here should enable new generations of implantable systems that can be integrated into the body at minimal cost and risk.biomedical electronics | microstimulator P rogress in semiconductor technology has led to electronic devices that can augment or replace physiological functions; their ability to be implanted for direct interaction with organ systems relies on overall miniaturization of the device for simplified delivery (e.g., via catheter or hypodermic needle) and access to interstitial spaces. Advances over the past few decades enable most components in a biomedical device, including electrodes, oscillators, memory, and wireless communication systems, to be integrated on tiny silicon chips. However, the energy required for electronic function remains substantial and the consumption density has not been matched by existing powering technologies (1). As a result, the vast bulk of most implantable electronic devices consists of energy storage or harvesting components.Although considerable progress has been made in energy storage technologies, batteries remain a major obstacle to miniaturization (2, 3) because their lifetimes are limited and highly constrained by the available volume, requiring periodic surgical replacement once the unit is depleted. Energy-harvesting strategies have been developed to eliminate batteries or to extend their function. Previous demonstrations include thermoelectric (4), piezoelectric (5-7), biopotential (8), or glucose (9, 10) power extraction. However, these methods are anatomically specific and, in their existing forms, yield power densities too low (<0.1 μW/mm 2 ) for a microimplant. Alternatively, energy can be transferred from an external source. I...

Our data indicate that recordings of leads V1-V3 of the 12-lead ECG on the parasternal second or third intercostal space would be helpful in diagnosing suspected patients with Brugada syndrome. The data suggest that Na+ channel blockers are capable of accentuating ST elevation in leads V1-V3.

Wireless powering could enable the long-term operation of advanced bioelectronic devices within the human body. Although both enhanced powering depth and device miniaturization can be achieved by shaping the field pattern within the body, existing electromagnetic structures do not provide the spatial phase control required to synthesize such patterns. Here, we describe the design and operation of conformal electromagnetic structures, termed phased surfaces, that interface with non-planar body surfaces and optimally modulate the phase response to enhance the performance of wireless powering. We demonstrate that the phased surfaces can wirelessly transfer energy across anatomically heterogeneous tissues in large animal models, powering miniaturized semiconductor devices (<12 mm3) deep within the body (>4 cm). As an illustration of in vivo operation, we wirelessly regulated cardiac rhythm by powering miniaturized stimulators at multiple endocardial sites in a porcine animal model.

Our data suggest that sympathetic stimulation produces a greater increase in both transmural and spatial dispersion of repolarization in LQT1 than in LQT2 syndrome, and this may explain why LQT1 patients are more sensitive to sympathetic stimulation.

Among the eukaryotes only plants and a number of fungi are able to synthesize biotin. Although initial events leading to the biosynthesis of biotin remain largely unknown, the final steps are known to occur in the mitochondria. Here we deleted the Aopex5 and Aopex7 genes encoding the receptors for peroxisomal targeting signals PTS1 and PTS2, respectively, in the filamentous fungus Aspergillus oryzae. In addition to exhibiting defects in the peroxisomal targeting of either PTS1 or PTS2 proteins, the deletion strains also displayed growth defects on minimal medium containing oleic acid as the sole carbon source. Unexpectedly, these peroxisomal transport-deficient strains also exhibited growth defects on minimal medium containing glucose as the sole carbon source that were remediated by the addition of biotin and its precursors, including 7-keto-8-aminopelargonic acid (KAPA). Genome database searches in fungi and plants revealed that BioF protein/KAPA synthase, one of the biotin biosynthetic enzymes, has a PTS1 sequence at the C terminus. Fungal ⌬bioF strains expressing the fungal and plant BioF proteins lacking PTS1 still exhibited growth defects in the absence of biotin, indicating that peroxisomal targeting of KAPA synthase is crucial for the biotin biosynthesis. Furthermore, in the plant Arabidopsis thaliana, AtBioF localized to the peroxisomes through recognition of its PTS1 sequence, suggesting involvement of peroxisomes in biotin biosynthesis in plants. Taken together we demonstrate a novel role for peroxisomes in biotin biosynthesis and suggest the presence of as yet unidentified peroxisomal proteins that function in the earlier steps of biotin biosynthesis.

Beta-blockade under normal sympathetic tone produces a greater decrease in TDR in the LQT1 form than in the LQT2 form, explaining the superior effectiveness of beta-blockers in LQT1 versus LQT2. Beta-blockers also suppress the influence of sympathetic stimulation in increasing TDR and SDR equally in LQT1 and LQT2 syndrome.

Wireless functionality is essential for the implementation of wearable systems, but its adaptation in stretchable electronic systems has had limited success. In this paper, the electromagnetic properties of stretchable serpentine mesh-based systems is studied, and this general strategy is used to produce high-performance stretchable microwave systems. Stretchable mechanics are enabled by converting solid metallic sections in conventional systems to subwavelength-scale serpentine meshes, followed by bonding to an elastomeric substrate. Compared to prior implementations of serpentine meshes in microwave systems, this conversion process is extended to arbitrary planar layouts, including those containing curvilinear shapes. A detailed theoretical analysis is also performed and a natural tradeoff is quantified between the stretching mechanics and microwave performance of these systems. To explore the translation of these concepts from theory to experiment, two types of stretchable microwave devices are fabricated and characterized: a stretchable far-field dipole antenna for communications and a stretchable midfield phased surface for the wireless powering of biomedical implanted devices.