628 research outputs found
Learning Dialogue Representations from Consecutive Utterances
Learning high-quality dialogue representations is essential for solving a
variety of dialogue-oriented tasks, especially considering that dialogue
systems often suffer from data scarcity. In this paper, we introduce Dialogue
Sentence Embedding (DSE), a self-supervised contrastive learning method that
learns effective dialogue representations suitable for a wide range of dialogue
tasks. DSE learns from dialogues by taking consecutive utterances of the same
dialogue as positive pairs for contrastive learning. Despite its simplicity,
DSE achieves significantly better representation capability than other dialogue
representation and universal sentence representation models. We evaluate DSE on
five downstream dialogue tasks that examine dialogue representation at
different semantic granularities. Experiments in few-shot and zero-shot
settings show that DSE outperforms baselines by a large margin. For example, it
achieves 13% average performance improvement over the strongest unsupervised
baseline in 1-shot intent classification on 6 datasets. We also provide
analyses on the benefits and limitations of our model.Comment: NAACL 2022 main conferenc
Exploiting differential Wnt target gene expression to generate a molecular biomarker for colorectal cancer stratification
OBJECTIVE
Pathological Wnt pathway activation is a conserved hallmark of colorectal cancer. Wnt-activating mutations can be divided into: i) ligand-independent (LI) alterations in intracellular signal transduction proteins (, β-catenin), causing constitutive pathway activation and ii) ligand-dependent (LD) mutations affecting the synergistic R-Spondin axis (, -fusions) acting through amplification of endogenous Wnt signal transmembrane transduction. Our aim was to exploit differential Wnt target gene expression to generate a mutation-agnostic biomarker for LD tumours.
DESIGN
We undertook harmonised multi-omic analysis of discovery (n=684) and validation cohorts (n=578) of colorectal tumours collated from publicly available data and the Stratification in Colorectal Cancer Consortium. We used mutation data to establish molecular ground truth and subdivide lesions into LI/LD tumour subsets. We contrasted transcriptional, methylation, morphological and clinical characteristics between groups.
RESULTS
Wnt disrupting mutations were mutually exclusive. Desmoplastic stromal upregulation of may compensate for absence of epithelial mutation in a subset of stromal-rich tumours. Key Wnt negative regulator genes were differentially expressed between LD/LI tumours, with targeted hypermethylation of some genes (, ) occurring even in CIMP-negative LD cancers. mRNA expression was used as a discriminatory molecular biomarker to distinguish LD/LI tumours (area under the curve >0.93).
CONCLUSIONS
Epigenetic suppression of appropriate Wnt negative feedback loops is selectively advantageous in LD tumours and differential expression in LD/LI lesions can be exploited as a molecular biomarker. Distinguishing between LD/LI tumour types is important; patients with LD tumours retain sensitivity to Wnt ligand inhibition and may be stratified at diagnosis to clinical trials of Porcupine inhibitors
Characterizing K2 Candidate Planetary Systems Orbiting Low-mass Stars. IV. Updated Properties for 86 Cool Dwarfs Observed during Campaigns 1–17
We present revised stellar properties for 172 K2 target stars that were identified as possible hosts of transiting planets during Campaigns 1–17. Using medium-resolution near-infrared spectra acquired with the NASA Infrared Telescope Facility/SpeX and Palomar/TripleSpec, we found that 86 of our targets were bona fide cool dwarfs, 74 were hotter dwarfs, and 12 were giants. Combining our spectroscopic metallicities with Gaia parallaxes and archival photometry, we derived photometric stellar parameters and compared them to our spectroscopic estimates. Although our spectroscopic and photometric radius and temperature estimates are consistent, our photometric mass estimates are systematically ΔM sstarf = 0.11 M ⊙ (34%) higher than our spectroscopic mass estimates for the least massive stars (M sstarf,phot < 0.4 M ⊙). Adopting the photometric parameters and comparing our results to parameters reported in the Ecliptic Plane Input Catalog, our revised stellar radii are ΔR sstarf = 0.15 R ⊙ (40%) larger, and our revised stellar effective temperatures are roughly ΔT eff = 65 K cooler. Correctly determining the properties of K2 target stars is essential for characterizing any associated planet candidates, estimating the planet search sensitivity, and calculating planet occurrence rates. Even though Gaia parallaxes have increased the power of photometric surveys, spectroscopic characterization remains essential for determining stellar metallicities and investigating correlations between stellar metallicity and planetary properties
Modelling Cognitive Decline in the Hypertension in the Very Elderly Trial [HYVET] and Proposed Risk Tables for Population Use
Although, on average, cognition declines with age, cognition in older adults is a dynamic process. Hypertension is associated with greater decline in cognition with age, but whether treatment of hypertension affects this is uncertain. Here, we modelled dynamics of cognition in relation to the treatment of hypertension, to see if treatment effects might better be discerned by a model that included baseline measures of cognition and consequent mortalityThis is a secondary analysis of the Hypertension in the Very Elderly Trial (HYVET), a double blind, placebo controlled trial of indapamide, with or without perindopril, in people aged 80+ years at enrollment. Cognitive states were defined in relation to errors on the Mini-Mental State Examination, with more errors signifying worse cognition. Change in cognitive state was evaluated using a dynamic model of cognitive transition. In the model, the probabilities of transitions between cognitive states is represented by a Poisson distribution, with the Poisson mean dependent on the baseline cognitive state. The dynamic model of cognitive transition was good (R(2) = 0.74) both for those on placebo and (0.86) for those on active treatment. The probability of maintaining cognitive function, based on baseline function, was slightly higher in the actively treated group (e.g., for those with the fewest baseline errors, the chance of staying in that state was 63% for those on treatment, compared with 60% for those on placebo). Outcomes at two and four years could be predicted based on the initial state and treatment.A dynamic model of cognition that allows all outcomes (cognitive worsening, stability improvement or death) to be categorized simultaneously detected small but consistent differences between treatment and control groups (in favour of treatment) amongst very elderly people treated for hypertension. The model showed good fit, and suggests that most change in cognition in very elderly people is small, and depends on their baseline state and on treatment. Additional work is needed to understand whether this modelling approach is well suited to the valuation of small effects, especially in the face of mortality differences between treatment groups.ClinicalTrials.gov NCT0012281
Estimating total body water content in suckling and lactating llamas (Lama glama) by isotope dilution
Total body water (TBW) in 17 suckling and six lactating llamas was estimated from isotope dilution at three different post natum and lactation stages using both 18O and deuterium oxide (D2O). In total, 69 TBW measurements were undertaken. While TBW in lactating dams, expressed in kilogram, remained stable during the three measurement periods (91.8 ± 15.0 kg), the body water fraction (TBW expressed in percent of body mass) increased slightly (P = 0.042) from 62.9% to 65.8%. In contrast, TBW (kilogram) in suckling llamas increased significantly (P < 0.001) with age and decreased slightly when expressed as a percentage of body mass (P = 0.016). Relating TBW to body mass across all animals yielded a highly significant regression equation (TBW in kilogram = 2.633 + 0.623 body mass in kilogram, P < 0.001, n = 69) explaining 99.5% of the variation. The water fraction instead decreased in a curve linear fashion with increasing body mass (TBW in percent of body mass = 88.23 body mass in kilogram−0.064, P < 0.001, R2 = 0.460). The present results on TBW can serve as reference values for suckling and lactating llamas, e.g., for the evaluation of fluid losses during disease. Additionally, the established regression equations can be used to predict TBW from body mass, providing that the body masses fall inside the range of masses used to derive the equations
Transforming entomology to adapt to global concerns: 2021 student debates
The 2021 Student Debates of the Entomological Society of America (ESA) were held at the Annual Meeting in Denver, CO. The event was organized by the Student Debates Subcommittee (SDS) of the Student Affairs Committee (SAC). The theme of the 2021 Student Debates was “Transforming Entomology to Adapt to Global Concerns”, with 3 topics. Each topic had an unbiased introduction and 2 teams. The debate topics were (i) Nonnative insect introduction is an ethical approach for counteracting proliferation and overpopulation of consumers, (ii) What is the best technology to control undesirable insect pests in urban and agricultural settings? and (iii) Compared to other solutions, like plant-based diets, insect farming is the best method to address rising human global food and nutrient supply demands. Unbiased introduction speakers and teams had approximately 6 months to prepare for their presentations
Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms
Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms
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