Towards more mature web maintenance practices for accessibility.

This paper proposes a need to differentiate Web maintenance from traditional software maintenance. The maintenance of a Web site is different than that of software as it is under constant maintenance and works by default in "modified environments". Building on the authors' previous work of automated quality measurement, a case study of large scale Web maintenance activity is described which focuses on a change to ensure that Web pages are accessible to users with disabilities. The results of the study show that organisations which have a clear and committed maintenance strategy and provide their staff with appropriate tools and training have better quality Web sites

The Role of Cutaneous Receptors in the Menton Tap Silent Period

The neuromuscular mechanisms of the electromyographic silent period are poorly understood but clinically significant. Our purpose was to isolate the contribution of cutaneous afferents from the chin to the latency and the duration of the EMG silent period. Under the conditions of our experiment, the afferents of the mental nerve have no observable influence on the latency or the duration of the silent period educed by a menton tap.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66492/2/10.1177_00220345790580011001.pd

S6K2-mediated regulation of TRBP as a determinant of miRNA expression in human primary lymphatic endothelial cells

MicroRNAs (miRNAs) are short non-coding RNAs that silence mRNAs. They are generated following transcription and cleavage by the DROSHA/DGCR8 and DICER/TRBP/PACT complexes. Although it is known that components of the miRNA biogenesis machinery can be phosphorylated, it remains poorly understood how these events become engaged during physiological cellular activation. We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells. We demonstrate the functional relevance of this interaction in primary human dermal lymphatic endothelial cells (HDLECs). Angiopoietin-1 (ANG1) can augment miRNA biogenesis in HDLECs through enhancing TRBP phosphorylation and expression in an S6K2-dependent manner. We propose that the S6K2/TRBP node controls miRNA biogenesis in HDLECs and provides a molecular link between the mTOR pathway and the miRNA biogenesis machinery

High-Density Amplicon Sequencing Identifies Community Spread and Ongoing Evolution of SARS-CoV-2 in the Southern United States

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is constantly evolving. Prior studies focused on high-case-density locations, such as the northern and western metropolitan areas of the United States. This study demonstrates continued SARS-CoV-2 evolution in a suburban southern region of the United States by high-density amplicon sequencing of symptomatic cases. 57% of strains carry the spike D614G variant, which is associated with higher genome copy numbers, and its prevalence expands with time. Four strains carry a deletion in a predicted stem loop of the 3′ UTR. The data are consistent with community spread within local populations and the larger continental United States. The data instill confidence in current testing sensitivity and validate “testing by sequencing” as an option to uncover cases, particularly nonstandard coronavirus disease 2019 (COVID-19) clinical presentations. This study contributes to the understanding of COVID-19 through an extensive set of genomes from a non-urban setting and informs vaccine design by defining D614G as a dominant and emergent SARS-CoV-2 isolate in the United States

Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc

Genomic basis for RNA alterations in cancer

Transcript alterations often result from somatic changes in cancer genomes. Various forms of RNA alterations have been described in cancer, including overexpression, altered splicing and gene fusions; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed 'bridged' fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer

Quasielastic (e,e′p) reaction on 12C,56Fe, and 197Au

We report the results from a systematic study of the quasielastic (e,e′p) reaction on 12C, 56Fe, and 197Au performed at Jefferson Lab. We have measured nuclear transparency and extracted spectral functions (corrected for radiation) over a Q2 range of 0.64–3.25 (GeV∕c)2 for all three nuclei. In addition, we have extracted separated longitudinal and transverse spectral functions at Q2 of 0.64 and 1.8 (GeV∕c)2 for these three nuclei (except for 197Au at the higher Q2). The spectral functions are compared to a number of theoretical calculations. The measured spectral functions differ in detail but not in overall shape from most of the theoretical models. In all three targets the measured spectral functions show considerable excess transverse strength at Q2=0.64 (GeV∕c)2, which is much reduced at 1.8 (GeV∕c)2

Separation of the Longitudinal and Transverse Cross Sections in the p(e, e′K+)Λ and p(e, e′K+)Σ0 Reactions

We report measurements of cross sections for the reaction p(e,e′K+)Y, for both the Λ and Σ0 hyperon states, at an invariant mass of W =1.84 GeV and four-momentum transfers 0.5 < Q2 < 2 (GeV/c)2. Data were taken for three values of virtual photon polarization ε, allowing the decom- position of the cross sections into longitudinal and transverse components. The Λ data is a revised analysis of prior work, whereas the Σ0 results have not been previously reported

Separated spectral functions for the quasifree 12C(e,e′p) reaction

A separation of the longitudinal and transverse 12C(e,e′p) cross sections in the quasifree region has been performed in parallel kinematics at Q2 of 0.64 and 1.8 GeV2 for initial proton momentum <80 MeV. The separated transverse and longitudinal spectral functions at Q2=0.64GeV2 show significant differences for missing energy between 25 and 60 MeV indicating a breakdown in the single nucleon knockout picture. The transverse spectral functions exhibit definite momentum transfer dependence

Biogeochemical silica mass balances in Lake Michigan and Lake Superior

Silica budgets for Lake Michigan and Lake Superior differ in several respects. Mass balance calculations for both lakes agree with previous studies in that permanent burial of biogenic silica in sediments may be only about 5% of the biogenic silica produced by diatoms. Because dissolution rates are large, good estimates of permanent burial of diatoms can not be obtained indirectly from the internal cycle of silica (silica uptake by diatoms and subsequent dissolution) but must be obtained from the sediment stratigraphy. The annual net production of biogenic silica in Lake Michigan requires 71% of the winter maximum silica reservoir which must be maintained primarily by internal cycling in this large lake whereas the comparable silica demand in Lake Superior is only 8.3%. The greater silica demand in Lake Michigan is the result of phosphorus enrichment which has increased diatom production. It is hypothesized that steady-state silica dynamics in Lake Michigan were disrupted by increased diatom production between 1955 and 1970 and that a new steady state based on silica-limited diatom production developed after 1970. Mass balance calculations for Lake Michigan show in contrast with previous work that the hypothesized water column silica depletion of 3.0 g · m −3 could have occurred even though 90% or more of the biogenic silica production is recycled.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42471/1/10533_2004_Article_BF02187199.pd