SETX (senataxin) is an RNA/DNA helicase that has been implicated in transcriptional regulation and the DNA damage response through resolution of R-loop structures. Mutations in SETX result in either of two distinct neurodegenerative disorders. SETX dominant mutations result in a juvenile form of amyotrophic lateral sclerosis (ALS) called ALS4, whereas recessive mutations are responsible for ataxia called ataxia with oculomotor apraxia type 2 (AOA2). How mutations in the same protein can lead to different phenotypes is still unclear. To elucidate AOA2 disease mechanisms, we first examined gene expression changes following SETX depletion. We observed the effects on both transcription and RNA processing, but surprisingly observed decreased R-loop accumulation in SETX-depleted cells. Importantly, we discovered a strong connection between SETX and the macroautophagy/autophagy pathway, reflecting a direct effect on transcription of autophagy genes. We show that SETX depletion inhibits the progression of autophagy, leading to an accumulation of ubiquitinated proteins, decreased ability to clear protein aggregates, as well as mitochondrial defects. Analysis of AOA2 patient fibroblasts also revealed a perturbation of the autophagy pathway. Our work has thus identified a novel function for SETX in the regulation of autophagy, whose modulation may have a therapeutic impact for AOA2.
This study investigates the reflection characteristics of a composite Artificial Magnetic Conductor (AMC) surface consisting of multiple orthogonal gradient AMC surfaces arranged in a two-dimensional periodic pattern. The gradient AMC surface in this study consists of square metal patches of variable size printed on a grounded dielectric substrate. Due to the orthogonal placement of the gradient AMC surface, the incident energy of a plane wave normally incident on the composite AMC surface will be reflected into four major lobes away from the impinging direction. To achieve a systematical design, a simple formula based on array antenna theory was developed to determine the reflection pattern of the gradient AMC surface illuminated by a normal incident plane wave. A time-domain full-wave simulation was also carried out to calculate the electromagnetic fields in the structure and the far-field patterns. The scattering patterns of the structure were measured in an electromagnetic anechoic chamber. Results confirm the design principle and procedures in this research. Since such a composite AMC surface can be easily fabricated using the standard printed circuit board technique without via-hole process, it may have potential applications in beam-steering and radar cross section reduction
In this paper, we investigated random telegraph noise (RTN) characteristics of gate-all-around poly-Si nanowire (NW) transistors with high-κ oxide/ metal-gate (HK/MG) stack. Distinct two-level RTN signals were measured on NW transistors with effective channel length of 150 nm and channel width of 30 nm. Values of time constants for charge emission from and capture by traps were extracted from measured RTN signals. We proposed a new theoretical scheme to evaluate the location and energy level of the corresponding trap. The trap was assessed to be present within the interfacial layer (IL) at a spatial location approximate 1 nm away from the IL/channel interface and 68 nm in proximity to the source side.
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