Background: Nav1.8 sodium channels, encoded by SCN10A, are preferentially expressed in nociceptive neurons and play an important role in human pain. Although rare gain-of-function variants in SCN10A have been identified in individuals with painful peripheral neuropathies, whether more common variants in SCN10A can have an effect at the channel level and at the dorsal root ganglion, neuronal level leading to a pain disorder or an altered normal pain threshold has not been determined. Results: Candidate single nucleotide polymorphism association approach together with experimental pain testing in human subjects was used to explore possible common SCN10A missense variants that might affect human pain sensitivity. We demonstrated an association between rs6795970 (G > A; p.Ala1073Val) and higher thresholds for mechanical pain in a discovery cohort (496 subjects) and confirmed it in a larger replication cohort (1005 female subjects). Functional assessments showed that although the minor allele shifts channel activation by À4.3 mV, a proexcitatory attribute, it accelerates inactivation, an antiexcitatory attribute, with the net effect being reduced repetitive firing of dorsal root ganglion neurons, consistent with lower mechanical pain sensitivity. Conclusions: At the association and mechanistic levels, the SCN10A single nucleotide polymorphism rs6795970 biases human pain sensitivity.
Abstract-Conventional GaN vertical devices, though promising for high-power applications, need expensive GaN substrates. Recently, low-cost GaN-on-Si vertical diodes have been demonstrated for the first time. This paper presents a systematic study to understand and control the OFF-state leakage current in the GaN-on-Si vertical diodes. Various leakage sources were investigated and separated, including leakage through the bulk drift region, passivation layer, etch sidewall, and transition layers. To suppress the leakage along the etch sidewall, an advanced edge termination technology has been developed by combining plasma treatment, tetramethylammonium hydroxide wet etching, and ion implantation. With this advanced edge termination technology, an OFF-state leakage current similar to Si, SiC, and GaN lateral devices has been achieved in the GaN-on-Si vertical diodes with over 300 V breakdown voltage and 2.9-MV/cm peak electric field. The origin of the remaining OFF-state leakage current can be explained by a combination of electron tunneling at the p-GaN/drift-layer interface and carrier hopping between dislocation traps. The low leakage current achieved in these devices demonstrates the great potential of the GaN-on-Si vertical device as a new low-cost candidate for high-performance power electronics.Index Terms-Edge termination, GaN-on-Si vertical device, leakage control, leakage origin, power electronics.
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