Speech-plans: Generating evaluative responses in spoken dialogue

Recent work on evaluation of spoken dialogue systems indicates that better algorithms are needed for the presentation of complex information in speech. Current dialogue systems often rely on presenting sets of options and their attributes sequentially. This places a large memory burden on users, who have to remember complex trade-offs between multiple options and their attributes. To address these problems we build on previous work using multiattribute decision theory to devise speech-planning algorithms that present usertailored summaries, comparisons and recommendations that allow users to focus on critical differences between options and their attributes. We discuss the differences between speech and text planning that result from the particular demands of the speech situation.

A Roberts Syndrome Individual With Differential Genotoxin Sensitivity and a DNA Damage Response Defect

© 2018 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 12 month embargo from date of publication (November 2018) in accordance with the publisher’s archiving policyPurpose Roberts syndrome (RBS) is a rare, recessively transmitted developmental disorder characterized by growth retardation, craniofacial abnormalities, and truncation of limbs. All affected individuals to date have mutations in the ESCO2 (establishment of cohesion 2) gene, a key regulator of the cohesin complex, which is involved in sister chromatid cohesion and DNA double-strand break (DSB) repair. Here we characterize DNA damage responses (DDRs) for the first time in an RBS-affected family. Methods and Materials Lymphoblastoid cell lines were established from an RBS family, including the proband and parents carrying ESCO2 mutations. Various DDR assays were performed on these cells, including cell survival, chromosome break, and apoptosis assays; checkpoint activation indicators; and measures of DNA breakage and repair. Results Cells derived from the RBS-affected individual showed sensitivity to ionizing radiation (IR) and mitomycin C–induced DNA damage. In this ESCO2 compound heterozygote, other DDRs were also defective, including enhanced IR-induced clastogenicity and apoptosis; increased DNA DSB induction; and a reduced capacity for repairing IR-induced DNA DSBs, as measured by γ-H2AX foci and the comet assay. Conclusions In addition to its developmental features, RBS can be, like ataxia telangiectasia, considered a DDR-defective syndrome, which contributes to its cellular, molecular, and clinical phenotype

Elongation of very long-chain (>C24) fatty acids in Clarias gariepinus: Cloning, functional characterization and tissue expression of elovl4 elongases

Elongation of very long-chain fatty acid 4 (Elovl4) proteins participate in the biosynthesis of very long-chain (>C24) saturated and polyunsaturated fatty acids (FA). Previous studies have shown that fish possess two different forms of Elovl4, termed Elovl4a and Elovl4b. The present study aimed to characterize both molecularly and functionally two elovl4 cDNA from the African catfish Clarias gariepinus. The results confirmed that C. gariepinus possessed two elovl4-like elongases with high homology to two previously characterized Elovl4 from Danio rerio, and thus they were termed accordingly as Elovl4a and Elovl4b. The C. gariepinus Elovl4a and Elovl4b have open reading frames (ORF) of 945 and 915 base pairs, respectively, encoding putative proteins of 314 and 304 amino acids, respectively. Functional characterization in yeast showed both Elovl4 enzymes have activity towards all the PUFA substrates assayed (18:4n-3, 18:3n-6, 20:5n-3, 20:4n-6, 22:5n-3, 22:4n-6 and 22:6n-3), producing elongated products of up to C36. Moreover, the C. gariepinus Elovl4a and Elovl4b were able to elongate very long-chain saturated FA (VLC-SFA) as denoted by increased levels of 28:0 and longer FA in yeast transformed with elovl4 ORF compared to control yeast. These results confirmed that C. gariepinus Elovl4 play important roles in the biosynthesis of very long-chain FA. Tissue distribution analysis of elovl4 mRNAs showed both genes were widely expressed in all tissues analyzed, with high expression of elovl4a in pituitary and brain, whereas female gonad and pituitary had the highest expression levels for elovl4b

Biosynthesis of long-chain polyunsaturated fatty acids in marine fish: Characterization of an Elovl4-like elongase from cobia Rachycentron canadum and activation of the pathway during early life stages

Marine fish, unlike freshwater species, have been generally considered to have a limited ability to biosynthesize long-chain polyunsaturated fatty acids (LC-PUFA) from C18 precursors due to apparent limited enzymatic activities involved in the pathway. Although LC-PUFA play important physiological roles throughout the entire life cycle, requirements for early life stages are especially high and provision of preformed LC-PUFA in egg lipids appears critical to support the formation of developing tissues where these compounds accumulate. No studies, however, have been conducted to explore the capability of marine fish embryos (here referring to life stages from zygote to the oesophagus opening) for de novo synthesis of the LC-PUFA required for normal growth and development. The present study aimed to investigate the activation of the LC-PUFA biosynthetic pathway during embryogenesis of the marine teleost cobia (Rachycentron canadum). First, a fatty acyl elongase with sequence similarity to mammalian elongase of very long-chain fatty acids 4 (Elovl4) was isolated, and its biochemical function characterized showing that it catalyzed the production of very long-chain fatty acids (VLC-FA) including both saturated and polyunsaturated fatty acids with chain lenghts ≥ 24 carbons. Notably, cobia Elovl4 was able to elongate 22:5n-3 to 24:5n-3 and thus could play a key role in the biosynthesis of docosahexaenoic acid (22:6n-3), a critical fatty acid in neural tissues. Subsequently, the fatty acid dynamics of embryos at different developmental stages and the temporal expression patterns of target genes including elovl4, and the formerly characterized elovl5 elongase and ∆6 fatty acyl desaturase, were analyzed in order to elucidate the overall activation of the LC-PUFA biosynthetic pathway in cobia embryos. Our results indicated that expression of the LC-PUFA biosynthetic pathway in cobia embryos is initiated at 12-18 hours post-fertilization

H2AX phosphorylation screen of cells from radiosensitive cancer patients reveals a novel DNA double-strand break repair cellular phenotype

BACKGROUND: About 1-5% of cancer patients suffer from significant normal tissue reactions as a result of radiotherapy (RT). It is not possible at this time to predict how most patients' normal tissues will respond to RT. DNA repair dysfunction is implicated in sensitivity to RT particularly in genes that mediate the repair of DNA double-strand breaks (DSBs). Phosphorylation of histone H2AX (phosphorylated molecules are known as gammaH2AX) occurs rapidly in response to DNA DSBs, and, among its other roles, contributes to repair protein recruitment to these damaged sites. Mammalian cell lines have also been crucial in facilitating the successful cloning of many DNA DSB repair genes; yet, very few mutant cell lines exist for non-syndromic clinical radiosensitivity (RS).\ud \ud METHODS: Here, we survey DNA DSB induction and repair in whole cells from RS patients, as revealed by gammaH2AX foci assays, as potential predictive markers of clinical radiation response.\ud \ud RESULTS: With one exception, both DNA focus induction and repair in cell lines from RS patients were comparable with controls. Using gammaH2AX foci assays, we identified a RS cancer patient cell line with a novel ionising radiation-induced DNA DSB repair defect; these data were confirmed by an independent DNA DSB repair assay.\ud \ud CONCLUSION: gammaH2AX focus measurement has limited scope as a pre-RT predictive assay in lymphoblast cell lines from RT patients; however, the assay can successfully identify novel DNA DSB repair-defective patient cell lines, thus potentially facilitating the discovery of novel constitutional contributions to clinical RS

Sub-Cycle Effects in Carrier-Envelope-Phase-Sensitive Photoemission from Plasmonic Nanoparticles

We study carrier-envelope-phase-sensitive (CEP-sensitive) photoemission from plasmonic nanoparticles illuminated with few-cycle laser pulses of varying intensity. The CEP- sensitive photocurrent exhibits antiresonant-like behavior due to competing emission from different optical half-cycles