Abstract: Provided herein are non-naturally occurring, broadly reactive antigens derived from influenza viruses that are immunogenic and capable of eliciting a broadly reactive immune response, e.g., a broadly reactive neutralizing antibody response, directed against influenza virus antigens following introduction into a subject. Also provided are non-naturally, broadly reactive immunogens, vaccines, virus particles, virus-like particles (VLPs) and compositions comprising the immunogens and vaccines. Methods of generating an immune response in a human or non-human subject by administering the immunogens, vaccines, VLPs, or compositions thereof are provided. In particular, the immunogens comprise broadly reactive hemagglutinin (HA) protein antigens or soluble HA protein antigens of influenza virus strains, such as H1 or H3.

Abstract: A neural interfacing device is disclosed. The neural interfacing device includes a microneedle electrode. The microneedle electrode includes a body having a void formed therein and a plurality of microneedles. The void surrounds the plurality of microneedles, and the plurality of microneedles are bent outward with respect to the body to form a three-dimensional microneedle electrode. Additionally, each of the plurality of microneedles is sized and shaped to penetrate a nerve epineurium.

Abstract: A neural interfacing device is disclosed. The neural interfacing device includes a microneedle electrode. The microneedle electrode includes a body having a void formed therein and a plurality of microneedles. The void surrounds the plurality of microneedles, and the plurality of microneedles are bent outward with respect to the body to form a three-dimensional microneedle electrode. Additionally, each of the plurality of microneedles is sized and shaped to penetrate a nerve epineurium.

Abstract: A neural interfacing device is disclosed. The neural interfacing device may include at least one microneedle electrode. The microneedle electrode may have one or more microneedles. The one or more microneedles may be shaped and positioned such that when the neural interfacing device is applied to a nerve, the one or more microneedles penetrate a nerve epineurium without any portion of the microneedle electrode penetrating any nerve axon beyond a depth of 500 micrometers.

Abstract: Disclosed are apparatus and methods that provide the ability to electrical stimulate a physical system, and actively eliminate interference with signal acquisition (artifacts) that arises from the stimulation. The technique implemented in the circuits and methods for eliminating interference connects a discharge path to a physical interface to the system to remove charge that is built-up during stimulation. By placing the discharge path in a feedback loop that includes a recording preamplifier and AC-coupling circuitry, the physical interface is brought back to its pre-stimulation offset voltage. The disclosed apparatus and methods may be used with piezoelectric transducers, ultrasound devices, optical diodes, and polarizable and non-polarizable electrodes. The disclosed apparatus can be employed in implantable devices, in vitro or in vivo setups with vertebrate and invertebrate neural tissue, muscle fibers, pancreatic islet cells, osteoblasts, osteoclasts, bacteria, algae, fungi, protists, and plants.

Abstract: Disclosed are apparatus and methods that provide the ability to electrical stimulate a physical system, and actively eliminate interference with signal acquisition (artifacts) that arises from the stimulation. The technique implemented in the circuits and methods for eliminating interference connects a discharge path to a physical interface to the system to remove charge that is built-up during stimulation. By placing the discharge path in a feedback loop that includes a recording preamplifier and AC-coupling circuitry, the physical interface is brought back to its pre-stimulation offset voltage. The disclosed apparatus and methods may be used with piezoelectric transducers, ultrasound devices, optical diodes, and polarizable and non-polarizable electrodes. The disclosed apparatus can be employed in implantable devices, in vitro or in vivo setups with vertebrate and invertebrate neural tissue, muscle fibers, pancreatic islet cells, osteoblasts, osteoclasts, bacteria, algae, fungi, protists, and plants.

Abstract: Implementations disclosed herein provide for a microneedle electrode system comprising a microneedle electrode patch connected to external electronics. The microneedle electrode patch comprises a first flexible substrate having a plurality of conductive pads disposed thereon, a plurality of three-dimensional, individually addressable microneedle electrode arrays where each array has a plurality of microneedles extending from an upper surface thereof and a lower surface adapted to contact a corresponding one of the plurality of conductive pads disposed on the first substrate, and a second flexible substrate having a plurality of openings defined therein dimensioned to accommodate at least a portion of the upper surface of the microneedle electrode array from which the microneedles extend.

Abstract: A neural interfacing device is disclosed. The neural interfacing device may include at least one microneedle electrode. The microneedle electrode may have one or more microneedles. The one or more microneedles may be shaped and positioned such that when the neural interfacing device is applied to a nerve, the one or more microneedles penetrate a nerve epineurium without any portion of the microneedle electrode penetrating any nerve axon beyond a depth of 500 micrometers.

Abstract: Disclosed are apparatus and methods that provide the ability to electrical stimulate a physical system, and actively eliminate interference with signal acquisition (artifacts) that arises from the stimulation. The technique implemented in the circuits and methods for eliminating interference connects a discharge path to a physical interface to the system to remove charge that is built-up during stimulation. By placing the discharge path in a feedback loop that includes a recording preamplifier and AC-coupling circuitry, the physical interface is brought back to its pre-stimulation offset voltage. The disclosed apparatus and methods may be used with piezoelectric transducers, ultrasound devices, optical diodes, and polarizable and non-polarizable electrodes. The disclosed apparatus can be employed in implantable devices, in vitro or in vivo setups with vertebrate and invertebrate neural tissue, muscle fibers, pancreatic islet cells, osteoblasts, osteoclasts, bacteria, algae, fungi, protists, and plants.

Abstract: Electrophysiology culture plates are provided and are formed from a transparent microelectrode array (MEA) plate. The MEA plate comprises a substrate, a first layer and a first insulating layer. The substrate has a plurality of vias extending from an upper to a lower surface, each via being in electrical contact with each of a plurality of contact pads disposed on the lower surface. The first layer is disposed on the upper surface of the substrate and has a plurality of MEA arrays in electrical communication with at least a first routing layer. Each MEA array comprises a plurality of reference electrodes and a plurality of microelectrodes and the first routing layer is in electrical communication with a select number of the plurality of vias. A first insulating layer is disposed on the first layer.

Abstract: Electrophysiology culture plates are provided and are formed from a transparent microelectrode array (MEA) plate. The MEA plate comprises a substrate, a first layer and a first insulating layer. The substrate has a plurality of vias extending from an upper to a lower surface, each via being in electrical contact with each of a plurality of contact pads disposed on the lower surface. The first layer is disposed on the upper surface of the substrate and has a plurality of MEA arrays in in electrical communication with at least a first routing layer. Each MEA array comprises a plurality of reference electrodes and a plurality of microelectrodes and the first routing layer is in electrical communication with a select number of the plurality of vias. A first insulating layer is disposed on the first layer.

Abstract: Electrophysiology culture plates are provided and are formed from a transparent micro-electrode array (MEA) plate. The MEA plate comprises a substrate, a first layer and a first insulating layer. The substrate has a plurality of vias extending from an upper to a lower surface, each via being in electrical contact with each of a plurality of contact pads disposed on the lower surface. The first layer is disposed on the upper surface of the substrate and has a plurality of MEA arrays in in electrical communication with at least a first routing layer. Each MEA array comprises a plurality of reference electrodes and a plurality of microelectrodes and the first routing layer is in electrical communication with a select number of the plurality of vias. A first insulating layer is disposed on the first layer.

Abstract: Electrophysiology culture plates are provided and are formed from a transparent microelectrode array (MEA) plate. The MEA plate comprises a substrate, a first layer and a first insulating layer. The substrate has a plurality of vias extending from an upper to a lower surface, each via being in electrical contact with each of a plurality of contact pads disposed on the lower surface. The first layer is disposed on the upper surface of the substrate and has a plurality of MEA arrays in in electrical communication with at least a first routing layer. Each MEA array comprises a plurality of reference electrodes and a plurality of microelectrodes and the first routing layer is in electrical communication with a select number of the plurality of vias. A first insulating layer is disposed on the first layer.

Abstract: Implementations disclosed herein provide for a microneedle electrode system comprising a microneedle electrode patch connected to external electronics. The microneedle electrode patch comprises a first flexible substrate having a plurality of conductive pads disposed thereon, a plurality of three-dimensional, individually addressable microneedle electrode arrays where each array has a plurality of microneedles extending from an upper surface thereof and a lower surface adapted to contact a corresponding one of the plurality of conductive pads disposed on the first substrate, and a second flexible substrate having a plurality of openings defined therein dimensioned to accommodate at least a portion of the upper surface of the microneedle electrode array from which the microneedles extend.

Abstract: Disclosed are apparatus and methods that provide the ability to electrical stimulate a physical system, and actively eliminate interference with signal acquisition (artifacts) that arises from the stimulation. The technique implemented in the circuits and methods for eliminating interference connects a discharge path to a physical interface to the system to remove charge that is built-up during stimulation. By placing the discharge path in a feedback loop that includes a recording preamplifier and AC-coupling circuitry, the physical interface is brought back to its pre-stimulation offset voltage. The disclosed apparatus and methods may be used with piezoelectric transducers, ultrasound devices, optical diodes, and polarizable and non-polarizable electrodes. The disclosed apparatus can be employed in implantable devices, in vitro or in vivo setups with vertebrate and invertebrate neural tissue, muscle fibers, pancreatic islet cells, osteoblasts, osteoclasts, bacteria, algae, fungi, protists, and plants.

Abstract: Disclosed are apparatus and methods that provide the ability to electrical stimulate a physical system, and actively eliminate interference with signal acquisition (artifacts) that arises from the stimulation. The technique implemented in the circuits and methods for eliminating interference connects a discharge path to a physical interface to the system to remove charge that is built-up during stimulation. By placing the discharge path in a feedback loop that includes a recording preamplifier and AC-coupling circuitry, the physical interface is brought back to its pre-stimulation offset voltage. The disclosed apparatus and methods may be used with piezoelectric transducers, ultrasound devices, optical diodes, and polarizable and non-polarizable electrodes. The disclosed apparatus can be employed in implantable devices, in vitro or in vivo setups with vertebrate and invertebrate neural tissue, muscle fibers, pancreatic islet cells, osteoblasts, osteoclasts, bacteria, algae, fungi, protists, and plants.

Abstract: Provided are compositions and methods for the treatment of myocardial dysfunction associated with SIRS or sepsis, which methods comprise the administration to a patient in need thereof of a composition comprising one or more adenosine deaminase (ADA) inhibitor and/or one or more xanthine oxidase (XO) inhibitor. Exemplified herein are methods for the treatment of myocardial dysfunction, which methods comprise the administration of a composition comprising the ADA inhibitor pentostatin and/or a composition comprising the XO inhibitor allopurinol. Advantageously, the methods disclosed herein that employ the administration of one or more ADA inhibitor(s) do not significantly affect cardiac TNF-? mRNA expression and/or protein levels.

Abstract: Shifter assemblies to be mounted onto a motor vehicle are provided. According to one embodiment, a shifter assembly comprises a mounting plate configured to be mounted onto a motor vehicle adjacent to a floorboard. A pivot assembly is connected to the mounting plate. The shifter assembly also comprises a first shifter lever comprising a pedal portion configured to accept a first shifter pedal, and a linkage portion coupled for pivotal movement with respect to the pivot assembly. A linkage assembly comprising first and second end portions is coupled to the linkage portion of the first shifter lever at the first end portion, and is pivotally coupled to a shifter spline at the second end portion. The motor vehicle is upshifted by pivoting the first shifter lever in a forward direction and downshifted by pivoting a second shifter lever secured to the shifter spline in a forward direction.