A Quantitative Approach to Investigating the Hypothesis of Prokaryotic Intron Loss

Using a novel method, we show that ordered triplets of motifs usually associated with spliceosomal intron recognition are underrepresented in the protein coding sequence of complete Thermotogae, archaeal and bacterial genomes. The underrepresentation observed does not extend to the noncoding strand, suggesting that the cause of the asymmetry is related to mRNA rather than DNA. Our data do not suggest that the underrepresentation is due to gene transfer from eukaryotes. We speculate that one possible explanation for these observations is that the protein coding sequence of Thermotogae, Archaea and Bacteria was at some time in the past subjected to selection against certain motifs appearing in an order which might initiate splicing in environments harboring a functional spliceosome. This is consistent with, but certainly does not prove, a hypothetical scenario in which at least some prokaryote lineages once possessed a functional spliceosome. Thus, we present a new quantitative method, observations obtained using the method, and a speculative discussion of a possible explanation of the observations

Nucleic and Amino Acid Sequences Support Structure-Based Viral Classification

Viral capsids ensure viral genome integrity by protecting the enclosed nucleic acids. Interactions between the genome and capsid and between individual capsid proteins (i.e., capsid architecture) are intimate and are expected to be characterized by strong evolutionary conservation. For this reason, a capsid structure-based viral classification has been proposed as a way to bring order to the viral universe. The seeming lack of sufficient sequence similarity to reproduce this classification has made it difficult to reject structural convergence as the basis for the classification. We reinvestigate whether the structure-based classification for viral coat proteins making icosahedral virus capsids is in fact supported by previously undetected sequence similarity. Since codon choices can influence nascent protein folding cotranslationally, we searched for both amino acid and nucleotide sequence similarity. To demonstrate the sensitivity of the approach, we identify a candidate gene for the pandoravirus capsid protein. We show that the structure-based classification is strongly supported by amino acid and also nucleotide sequence similarities, suggesting that the similarities are due to common descent. The correspondence between structure-based and sequence-based analyses of the same proteins shown here allow them to be used in future analyses of the relationship between linear sequence information and macromolecular function, as well as between linear sequence and protein folds. IMPORTANCE Viral capsids protect nucleic acid genomes, which in turn encode capsid proteins. This tight coupling of protein shell and nucleic acids, together with strong functional constraints on capsid protein folding and architecture, leads to the hypothesis that capsid protein-coding nucleotide sequences may retain signatures of ancient viral evolution. We have been able to show that this is indeed the case, using the major capsid proteins of viruses forming icosahedral capsids. Importantly, we detected similarity at the nucleotide level between capsid protein-coding regions from viruses infecting cells belonging to all three domains of life, reproducing a previously established structure-based classification of icosahedral viral capsids.Peer reviewe

Method and apparatus for detecting flaws and defects in heat seals

Flaws and defects in heat seals formed between sheets of translucent film are identified by optically examining consecutive lateral sections of the seal along the seal length. Each lateral seal section is illuminated and an optical sensor array detects the intensity of light transmitted through the seal section for the purpose of detecting and locating edges in the heat seal. A line profile for each consecutive seal section is derived having an amplitude proportional to the change in light intensity across the seal section. Instances in the derived line profile where the amplitude is greater than a threshold level indicate the detection of a seal edge. The detected edges in each derived line profile are then compared to a preset profile edge standard to identify the existence of a flaw or defect

Smart-Cut Layer Transfer of Single-Crystal SiC Using Spin-on-Glass

The authors demonstrate “smart-cut”-type layer transfer of single-crystal silicon carbide (SiC) by using spin-on-glass (SoG) as an adhesion layer. Using SoG as an adhesion layer is desirable because it can planarize the surface, facilitate an initial low temperature bond, and withstand the thermal stresses at high temperature where layer splitting occurs (800–900 °C). With SoG, the bonding of wafers with a relatively large surface roughness of 7.5–12.5 Å rms can be achieved. This compares favorably to direct (fusion) wafer bonding, which usually requires extremely low roughness (\u3c2 Å rms), typically achieved using chemical mechanical polishing (CMP) after implantation. The higher roughness tolerance of the SoG layer transfer removes the need for the CMP step, making the process more reliable and affordable for expensive materials like SiC. To demonstrate the reliability of the smart-cut layer transfer using SoG, we successfully fabricated a number of suspended MEMS structures using this technology

New Universality Classes for Two-Dimensional σ\sigma-Models

We argue that the two-dimensional $O(N)$-invariant lattice $\sigma$-model with mixed isovector/isotensor action has a one-parameter family of nontrivial continuum limits, only one of which is the continuum $\sigma$-model constructed by conventional perturbation theory. We test the proposed scenario with a high-precision Monte Carlo simulation for $N=3,4$ on lattices up to $512 \times 512$, using a Wolff-type embedding algorithm. [CPU time $\approx$ 7 years IBM RS-6000/320H] The finite-size-scaling data confirm the existence of the predicted new family of continuum limits. In particular, the $RP^{N-1}$ and $N$-vector models do not lie in the same universality class.Comment: 10 pages (includes 2 figures), 211176 bytes Postscript, NYU-TH-93/07/03, IFUP-TH 34/9

Hardness Assurance for Total Dose and Dose Rate Testing of a State-of-the-Art Off-Shore 32 nm SOI CMOS Processor

No abstract availabl

Interventions in measles outbreaks: the potential reduction in cases associated with school suspension and vaccination interventions

Background: Measles is resurgent in the US, with more cases in 2019 than any year since 1992. Many of the cases were concentrated in three outbreaks in New York and Washington states, where local governments enacted intervention strategies in an attempt to limit the spread of measles. Regulations differed by location, suggesting guidance on the optimal interventions may be beneficial. Methods: We simulate the daily interactions of the populations of six metropolitan areas of Texas, US, using an agent-based model. The real-life vaccination rates of each school in these metropolitan areas are applied to simulated equivalents. A single case of measles is introduced to the population and the resulting number of cases counted. A range of public health interventions, focused on suspending unvaccinated students and mandatory vaccinations, were simulated during measles outbreaks and the reduction in the number of measles cases, relative to no intervention, recorded. Interventions were simulated only in schools with measles cases and in all schools in each metropolitan area. Results: Suspending unvaccinated students from school was associated with the greatest reduction in measles cases. In a plausible worst-case outbreak scenario, the number of cases is forecast to reduce by 68-96%. Interventions targeting all schools in a metropolitan area is not found to be associated with fewer measles cases than only targeting schools with measles cases, at 2018 vaccination rates. Targeting all schools also increases the cumulative number of school days missed by suspended students by a factor of 10-100, depending on the metropolitan area, compared to targeting only schools with measles cases. If vaccination rates drop 5% in the schools which are under-vaccinated in 2018, metropolitan area-wide interventions are forecast to be associated with fewer cases than school-specific interventions. Conclusions: Interventions that are quickly implemented and widely followed may reduce the size of measles outbreaks by up 96%. If vaccination rates continue to fall in Texas, metropolitan area-wide interventions should be considered in the event of an outbreak

Whole exome sequencing combined with linkage analysis identifies a novel 3 bp deletion in NR5A1

Disorders of sex development (DSDs) encompass a broad spectrum of conditions affecting the development of the gonads and genitalia. The underlying causes for DSDs include gain or loss of function variants in genes responsible for gonad development or steroidogenesis. Most patients with DSD have an unknown genetic etiology and cannot be given an

Deficiency of the two-pore-domain potassium channel TREK-1 promotes hyperoxia-induced lung injury

Copyright © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins. Objectives: We previously reported the expression of the twoporedomain K+ channel TREK-1 in lung epithelial cells and proposed a role for this channel in the regulation of alveolar epithelial cytokine secretion. In this study, we focused on investigating the role of TREK-1 in vivo in the development of hyperoxia-induced lung injury. Design: Laboratory animal experiments. Setting: University research laboratory. Subjects: Wild-type and TREK-1-deficient mice. Interventions: Mice were anesthetized and exposed to 1) room air, no mechanical ventilation, 2) 95% hyperoxia for 24 hours, and 3) 95% hyperoxia for 24 hours followed by mechanical ventilation for 4 hours. Measurements and Main Results: Hyperoxia exposure accentuated lung injury in TREK-1-deficient mice but not controls, resulting in increase in lung injury scores, bronchoalveolar lavage fluid cell numbers, and cellular apoptosis and a decrease in quasi-static lung compliance. Exposure to a combination of hyperoxia and injurious mechanical ventilation resulted in further morphological lung damage and increased lung injury scores and bronchoalveolar lavage fluid cell numbers in control but not TREK-1-deficient mice. At baseline and after hyperoxia exposure, bronchoalveolar lavage cytokine levels were unchanged in TREK-1-deficient mice compared with controls. Exposure to hyperoxia and mechanical ventilation resulted in an increase in bronchoalveolar lavage interleukin-6, monocyte chemotactic protein-1, and tumor necrosis factor-á levels in both mouse types, but the increase in interleukin-6 and monocyte chemotactic protein-1 levels was less prominent in TREK-1-deficient mice than in controls. Lung tissue macrophage inflammatory protein-2, keratinocytederived cytokine, and interleukin-1β gene expression was not altered by hyperoxia in TREK-1-deficient mice compared with controls. Furthermore, we show for the first time TREK-1 expression on alveolar macrophages and unimpaired tumor necrosis factor-á secretion from TREK-1-deficient macrophages. Conclusions: TREK-1 deficiency resulted in increased sensitivity of lungs to hyperoxia, but this effect is less prominent if overwhelming injury is induced by the combination of hyperoxia and injurious mechanical ventilation. TREK-1 may constitute a new potential target for the development of novel treatment strategies against hyperoxiainduced lung injury