Singleton-Merten syndrome (SMS) is an autosomal-dominant multi-system disorder characterized by dental dysplasia, aortic calcification, skeletal abnormalities, glaucoma, psoriasis, and other conditions. Despite an apparent autosomal-dominant pattern of inheritance, the genetic background of SMS and information about its phenotypic heterogeneity remain unknown. Recently, we found a family affected by glaucoma, aortic calcification, and skeletal abnormalities. Unlike subjects with classic SMS, affected individuals showed normal dentition, suggesting atypical SMS. To identify genetic causes of the disease, we performed exome sequencing in this family and identified a variant (c.1118A>C [p.Glu373Ala]) of DDX58, whose protein product is also known as RIG-I. Further analysis of DDX58 in 100 individuals with congenital glaucoma identified another variant (c.803G>T [p.Cys268Phe]) in a family who harbored neither dental anomalies nor aortic calcification but who suffered from glaucoma and skeletal abnormalities. Cys268 and Glu373 residues of DDX58 belong to ATP-binding motifs I and II, respectively, and these residues are predicted to be located closer to the ADP and RNA molecules than other nonpathogenic missense variants by protein structure analysis. Functional assays revealed that DDX58 alterations confer constitutive activation and thus lead to increased interferon (IFN) activity and IFN-stimulated gene expression. In addition, when we transduced primary human trabecular meshwork cells with c.803G>T (p.Cys268Phe) and c.1118A>C (p.Glu373Ala) mutants, cytopathic effects and a significant decrease in cell number were observed. Taken together, our results demonstrate that DDX58 mutations cause atypical SMS manifesting with variable expression of glaucoma, aortic calcification, and skeletal abnormalities without dental anomalies.

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Recently reported observations of filamentation during high power microwaves breakdown of near-atmospheric pressure gas are explained using a one-dimensional fluid model coupled to a theoretical wave-plasma model. This self-consistent treatment allows for time-dependent effects, plasma growth and diffusion, and partial absorption and reflection of waves. Simulation results, consistent with experiments, show the evolution of the plasma filaments spaced less than one-quarter wavelength, the sequential discrete light emission propagating back toward the source, and the diffusion and decay of the plasma. The model allows examination of many features not easily obtained experimentally, including dependence on field strength and frequency, pressure, and gas composition, which influence the breakdown and emission properties, including the spacing and speed of propagation of the filaments.

Plasma etching of high aspect ratio (HAR) features, typically vias, is a critical step in the fabrication of high capacity memory. With aspect ratios (ARs) exceeding 50 (and approaching 100), maintaining critical dimensions (CDs) while eliminating or diminishing twisting, contact-edge-roughening, and aspect ratio dependent etching (ARDE) becomes challenging. Integrated reactor and feature scale modeling was used to investigate the etching of HAR features in SiO 2 with ARs up to 80 using tri-frequency capacitively coupled plasmas sustained in Ar/C 4 F 8 /O 2 mixtures. In these systems, the fluxes of neutral radicals to the wafer exceed the fluxes of ions by 1-2 orders of magnitude due to lower threshold energies for dissociation compared with ionization. At low ARs (<5), these abundant fluxes of CF x and C x F y radicals to the etch front passivate the oxide to form a complex which is then removed by energetic species (ions and hot neutrals) through chemically enhanced reactive etching, resulting in the formation of gas phase SiF x , CO x , and COF. As the etching proceeds into higher ARs, the fractional contribution of physical sputtering to oxide removal increases as the fluxes of energetic species to the etch front surpass those of the conduction constrained CF x and C x F y radicals. The instantaneous etch rate of oxide decreases with increasing aspect ratio (ARDE effect) due to decreased fluxes of energetic species and decreased power delivered by these species to the etch front. As the etch rate of photoresist (PR) is independent of AR, maintaining CDs by avoiding undercut and bowing requires high SiO 2-over-PR selectivity, which in turn requires a minimum thickness of the PR at the end of etching. Positive ions with narrow angular distributions typically deposit charge on the bottom of low AR features, producing a maximum in positive electric potential on the bottom of the feature. For high AR features, grazing incidence collisions of ions on sidewalls depositing charge produce electric potentials with maxima on the sidewalls (as opposed to the bottom) of the feature.

Recently, conjoined genes (CGs) have emerged as important genetic factors necessary for understanding the human genome. However, their formation mechanism and precise structures have remained mysterious. Based on a detailed structural analysis of 57 human CG transcript variants (CGTVs, discovered in this study) and all (833) known CGs in the human genome, we discovered that the poly(A) signal site from the upstream parent gene region is completely removed via the skipping or truncation of the final exon; consequently, CG transcription is terminated at the poly(A) signal site of the downstream parent gene. This result led us to propose a novel mechanism of CG formation: the complete removal of the poly(A) signal site from the upstream parent gene is a prerequisite for the CG transcriptional machinery to continue transcribing uninterrupted into the intergenic region and downstream parent gene. The removal of the poly(A) signal sequence from the upstream gene region appears to be caused by a deletion or truncation mutation in the human genome rather than post-transcriptional trans-splicing events. With respect to the characteristics of CG sequence structures, we found that intergenic regions are hot spots for novel exon creation during CGTV formation and that exons farther from the intergenic regions are more highly conserved in the CGTVs. Interestingly, many novel exons newly created within the intergenic and intragenic regions originated from transposable element sequences. Additionally, the CGTVs showed tumor tissue-biased expression. In conclusion, our study provides novel insights into the CG formation mechanism and expands the present concepts of the genetic structural landscape, gene regulation, and gene formation mechanisms in the human genome.