This paper describes the development of a high-density electronic interface to the central nervous system. Silicon micromachined electrode arrays now permit the long-term monitoring of neural ...activity in vivo as well as the insertion of electronic signals into neural networks at the cellular level. Efforts to understand and engineer the biology of the implant/tissue interface are also underway. These electrode arrays are facilitating significant advances in our understanding of the nervous system, and merged with on-chip circuitry, signal processing, microfluidics, and wireless interfaces, they are forming the basis for a family of neural prostheses for the possible treatment of disorders such as blindness, deafness, paralysis, severe epilepsy, and Parkinson's disease.
Parallel recording of neuronal activity in the behaving animal is a prerequisite for our understanding of neuronal representation and storage of information. Here we describe the development of ...micro-machined silicon microelectrode arrays for unit and local field recordings. The two-dimensional probes with 96 or 64 recording sites provided high-density recording of unit and field activity with minimal tissue displacement or damage. The on-chip active circuit eliminated movement and other artifacts and greatly reduced the weight of the headgear. The precise geometry of the recording tips allowed for the estimation of the spatial location of the recorded neurons and for high-resolution estimation of extracellular current source density. Action potentials could be simultaneously recorded from the soma and dendrites of the same neurons. Silicon technology is a promising approach for high-density, high-resolution sampling of neuronal activity in both basic research and prosthetic devices.
Gamma frequency oscillations (30–100 Hz) have been suggested to underlie various cognitive and motor functions. Here, we examine the generation of gamma oscillation currents in the hippocampus, using ...two-dimensional, 96-site silicon probes. Two gamma generators were identified, one in the dentate gyrus and another in the CA3-CA1 regions. The coupling strength between the two oscillators varied during both theta and nontheta states. Both pyramidal cells and interneurons were phase-locked to gamma waves. Anatomical connectivity, rather than physical distance, determined the coupling strength of the oscillating neurons. CA3 pyramidal neurons discharged CA3 and CA1 interneurons at latencies indicative of monosynaptic connections. Intrahippocampal gamma oscillation emerges in the CA3 recurrent system, which entrains the CA1 region via its interneurons.
This work presents a microsystem that utilizes inductive power and data transfer through a backscatter-modulated carrier and a transducer interface that monitors its environment through embedded ...capacitive transducers. Formed on a single chip, transducers for temperature, pressure, and relative humidity are realized using a silicon-on-glass process that combines anodic bonding and a silicon-gold eutectic to realize vacuum-sealed cavities with low-impedance (6 /spl Omega/) electrical feedthroughs. Temperature is sensed capacitively using a row of Si/Au bimorph beams that produce a sensitivity of 15 fF//spl deg/C from 20 to 100/spl deg/C. The absolute pressure sensors have a sensitivity of 15 fF/torr and a range from 500 to 1200 torr, while the relative humidity sensor responds with 39 fF/%RH from 20 to 95%RH. A relaxation oscillator implements low-power capacitance-to-frequency conversion on a second chip with a sensitivity of 750 Hz/pF at 10 kHz, forming a 341 /spl mu/W transducer interface. The system is remotely powered by a 3-MHz carrier and has a volume of 32 mm/sup 3/, including the hybrid antenna wound around the perimeter of the system.
A 256-site, fully implantable, 3-D neural recording microsystem has been developed. The microsystem incorporates four active neural probes with integrated circuitry for site selection, amplification, ...and multiplexing. The probes drive an embedded data-compression ASIC that successfully detects neural spikes in the presence of neural and circuit noise. The spike detection ASIC achieves a factor of 12 bandwidth reduction while preserving the key features of the action potential waveshape necessary for spike discrimination. This work extends the total number of neural channels that can be recorded across a transcutaneous inductively coupled wireless link from 25 to 312. When a spike is detected, this ASIC serially shifts the 5-bit amplitude and 5-bit address of the spike off of the chip over a single 2.5 Mb/s wired or wireless line. The spike detection ASIC occupies 6 mm/sup 2/ in 0.5 /spl mu/m features and consumes 2.6 mW while the entire microsystem consumes 5.4 mW of power from a 3-V supply.
The use of foliar fungicides on field corn has increased greatly over the past 5 years in the United States in an attempt to increase yields, despite limited evidence that use of the fungicides is ...consistently profitable. To assess the value of using fungicides in grain corn production, random-effects meta-analyses were performed on results from foliar fungicide experiments conducted during 2002 to 2009 in 14 states across the United States to determine the mean yield response to the fungicides azoxystrobin, pyraclostrobin, propiconazole + trifloxystrobin, and propiconazole + azoxystrobin. For all fungicides, the yield difference between treated and nontreated plots was highly variable among studies. All four fungicides resulted in a significant mean yield increase relative to the nontreated plots (P < 0.05). Mean yield difference was highest for propiconazole + trifloxystrobin (390 kg/ha), followed by propiconazole + azoxystrobin (331 kg/ha) and pyraclostrobin (256 kg/ha), and lowest for azoxystrobin (230 kg/ha). Baseline yield (mean yield in the nontreated plots) had a significant effect on yield for propiconazole + azoxystrobin (P < 0.05), whereas baseline foliar disease severity (mean severity in the nontreated plots) significantly affected the yield response to pyraclostrobin, propiconazole + trifloxystrobin, and propiconazole + azoxystrobin but not to azoxystrobin. Mean yield difference was generally higher in the lowest yield and higher disease severity categories than in the highest yield and lower disease categories. The probability of failing to recover the fungicide application cost (ploss) also was estimated for a range of grain corn prices and application costs. At the 10-year average corn grain price of $0.12/kg ($2.97/bushel) and application costs of $40 to 95/ha, ploss for disease severity <5% was 0.55 to 0.98 for pyraclostrobin, 0.62 to 0.93 for propiconazole + trifloxystrobin, 0.58 to 0.89 for propiconazole + azoxystrobin, and 0.91 to 0.99 for azoxystrobin. When disease severity was >5%, the corresponding probabilities were 0.36 to 95, 0.25 to 0.69, 0.25 to 0.64, and 0.37 to 0.98 for the four fungicides. In conclusion, the high ploss values found in most scenarios suggest that the use of these foliar fungicides is unlikely to be profitable when foliar disease severity is low and yield expectation is high.
We analyze (2+1)-dimensional gravity with a Chern–Simons term and a negative cosmological constant, primarily at the weak field level. The full theory is expressible as the sum of two higher ...derivative SL(2,R) “vector” Chern–Simons terms, while the physical bulk degrees of freedom correspond to a single massive scalar field, just as for Λ=0. The interplay of Λ and the mass parameter μ can be studied, and any physical mass—including the conformal value with null propagation—is accessible by tuning μ. The single bulk mode yields a complete set of normalizable positive energy wave packets, as long as one chooses the usual, “wrong” sign of G necessary to connect smoothly with the known Λ=0 limit. The chiral Chern–Simons coupling leads to gauge invariant linearized curvatures propagating with chirality-dependent masses. Linearized metric fluctuations have a finite asymptotic Fefferman–Graham expansion about the Poincaré metric for any mass value greater or equal to a “critical” one, where various amusing effects appear, such as vanishing of one of the two “vector” Chern–Simons terms and an equivalence between tensor and vector excitations. We also find a set of chiral, pp-wave metrics that exactly solve the full nonlinear equations.
Abstract
Adolescent idiopathic scoliosis (AIS) is the most common musculoskeletal disorder of childhood development. The genetic architecture of AIS is complex, and the great majority of risk factors ...are undiscovered. To identify new AIS susceptibility loci, we conducted the first genome-wide meta-analysis of AIS genome-wide association studies, including 7956 cases and 88 459 controls from 3 ancestral groups. Three novel loci that surpassed genome-wide significance were uncovered in intragenic regions of the CDH13 (P-value_rs4513093 = 1.7E-15), ABO (P-value_ rs687621 = 7.3E-10) and SOX6 (P-value_rs1455114 = 2.98E-08) genes. Restricting the analysis to females improved the associations at multiple loci, most notably with variants within CDH13 despite the reduction in sample size. Genome-wide gene-functional enrichment analysis identified significant perturbation of pathways involving cartilage and connective tissue development. Expression of both SOX6 and CDH13 was detected in cartilage chondrocytes and chromatin immunoprecipitation sequencing experiments in that tissue revealed multiple HeK27ac-positive peaks overlapping associated loci. Our results further define the genetic architecture of AIS and highlight the importance of vertebral cartilage development in its pathogenesis.
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