380 research outputs found
Online and Offline Evaluation in Search Clarification
The effectiveness of clarification question models in engaging users within
search systems is currently constrained, casting doubt on their overall
usefulness. To improve the performance of these models, it is crucial to employ
assessment approaches that encompass both real-time feedback from users (online
evaluation) and the characteristics of clarification questions evaluated
through human assessment (offline evaluation). However, the relationship
between online and offline evaluations has been debated in information
retrieval. This study aims to investigate how this discordance holds in search
clarification. We use user engagement as ground truth and employ several
offline labels to investigate to what extent the offline ranked lists of
clarification resemble the ideal ranked lists based on online user engagement.Comment: 27 page
SpeakerLDA: Discovering Topics in Transcribed Multi-Speaker Audio Contents
ABSTRACT Topic models such as Latent Dirichlet Allocation (LDA
The impact of mergers on relaxed X-ray clusters - III. Effects on compact cool cores
(Abridged) We use the simulations presented in Poole et al. 2006 to examine
the effects of mergers on compact cool cores in X-ray clusters. We propose a
scheme for classifying the morphology of clusters based on their surface
brightness and entropy profiles. Three dominant morphologies emerge: two
hosting compact cores and central temperatures which are cool (CCC systems) or
warm (CWC systems) and one hosting extended cores which are warm (EWC systems).
We find that CCC states are disrupted only after direct collisions between
cluster cores in head-on collisions or during second pericentric passage in
off-axis mergers. By the time they relax, our remnant cores have generally been
heated to warm core (CWC or EWC) states but subsequently recover CCC states.
The only case resulting in a long-lived EWC state is a slightly off-axis 3:1
merger for which the majority of shock heating occurs during the accretion of a
low-entropy stream formed from the disruption of the secondary's core.
Compression prevents core temperatures from falling until after relaxation thus
explaining the observed population of relaxed CWC systems with no need to
invoke AGN feedback. The morphological segregation observed in the L_x-T_x and
beta-r_c scaling relations is reflected in our simulations as well. However,
none of the cases we have studied produce sufficiently high remnant central
entropies to account for the most under-luminous EWC systems observed. Lastly,
systems which initially host central metallicity gradients do not yield merger
remnants with flat metallicity profiles. Taken together, these results suggest
that once formed, compact core systems are remarkably stable against disruption
from mergers. It remains to be demonstrated exactly how the sizable observed
population of extended core systems was formed.Comment: 19 pages, 8 figures, submitted for publication in MNRA
Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity
Poly(ADP-ribose) polymerase (PARP) superfamily members covalently link either a single ADP-ribose (ADPR) or a chain of ADPR units to proteins using NAD as the source of ADPR. Although the well-known poly(ADP-ribosylating) (PARylating) PARPs primarily function in the DNA damage response, many noncanonical mono(ADP-ribosylating) (MARylating) PARPs are associated with cellular antiviral responses. We recently demonstrated robust up-regulation of several PARPs following infection with murine hepatitis virus (MHV), a model coronavirus. Here we show that SARS-CoV-2 infection strikingly up-regulates MARylating PARPs and induces the expression of genes encoding enzymes for salvage NAD synthesis from nicotinamide (NAM) and nicotinamide riboside (NR), while down-regulating other NAD biosynthetic pathways. We show that overexpression of PARP10 is sufficient to depress cellular NAD and that the activities of the transcriptionally induced enzymes PARP7, PARP10, PARP12 and PARP14 are limited by cellular NAD and can be enhanced by pharmacological activation of NAD synthesis. We further demonstrate that infection with MHV induces a severe attack on host cell NAD+ and NADP+. Finally, we show that NAMPT activation, NAM, and NR dramatically decrease the replication of an MHV that is sensitive to PARP activity. These data suggest that the antiviral activities of noncanonical PARP isozyme activities are limited by the availability of NAD and that nutritional and pharmacological interventions to enhance NAD levels may boost innate immunity to coronaviruses
Transmission routes of rare seasonal diseases: the case of norovirus infections
Norovirus (NoV) is the most commonly recognized cause of acute gastroenteritis, with over a million cases globally per year. While usually self-limiting, NoV poses a substantial economic burden because it is highly contagious and there are multiple transmission routes. Infection occurs through inhalation of vomitus; faecal-oral spread; and food, water and environmental contamination. While the incidence of the disease is predictably seasonal, much less is known about the relative contribution of the various exposure pathways in causing disease. Additionally, asymptomatic excretion and viral shedding make forecasting disease burden difficult. We develop a novel stochastic dynamic network model to investigate the contributions of different transmission pathways in multiple coupled social networks representing schools, hospitals, care-homes and family households in a community setting. We analyse how the networks impact on transmission. We used ward-level demographic data from Northumberland, UK to create a simulation cohort. We compared the results with extant data on NoV cases from the IID2 study. Connectivity across the simulated cohort was high. Cases of NoV showed marked seasonality, peaking in early winter and declining through the summer. For the first time, we show that fomites and food appear to be the most important exposure routes in determining the population burden of disease. This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’. This theme issue is linked with the earlier issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’
Environmentally relevant iron oxide nanoparticles produce limited acute pulmonary effects in rats at realistic exposure levels
Iron is typically the dominant metal in the ultrafine fraction of airborne particulate matter.
Various studies have investigated the toxicity of inhaled nano-sized iron oxide particles (FeOxNPs)
but their results have been contradictory, with some indicating no or minor effects and others finding
effects including oxidative stress and inflammation. Most studies, however, did not use materials
reflecting the characteristics of FeOxNPs present in the environment. We, therefore, analysed the
potential toxicity of FeOxNPs of different forms (Fe3O4
, α-Fe2O3 and γ-Fe2O3
) reflecting the characteristics of high iron content nano-sized particles sampled from the environment, both individually
and in a mixture (FeOx-mix). A preliminary in vitro study indicated Fe3O4 and FeOx-mix were more
cytotoxic than either form of Fe2O3
in human bronchial epithelial cells (BEAS-2B). Follow-up in vitro
(0.003, 0.03, 0.3 µg/mL, 24 h) and in vivo (Sprague–Dawley rats, nose-only exposure, 50 µg/m3 and
500 µg/m3
, 3 h/d × 3 d) studies therefore focused on these materials. Experiments in vitro explored
responses at the molecular level via multi-omics analyses at concentrations below those at which
significant cytotoxicity was evident to avoid detection of responses secondary to toxicity. Inhalation
experiments used aerosol concentrations chosen to produce similar levels of particle deposition
on the airway surface as were delivered in vitro. These were markedly higher than environmental
concentrations. No clinical signs of toxicity were seen nor effects on BALF cell counts or LDH
levels. There were also no significant changes in transcriptomic or metabolomic responses in lung or
BEAS-2B cells to suggest adverse effects
A multivariable Mendelian randomization analysis investigating smoking and alcohol consumption in oral and oropharyngeal cancer
The independent effects of smoking and alcohol in head and neck cancer are not clear, given the strong association between these risk factors. Their apparent synergistic effect reported in previous observational studies may also underestimate independent effects. Here we report multivariable Mendelian randomization performed in a two-sample approach using summary data on 6,034 oral/oropharyngeal cases and 6,585 controls from a recent genome-wide association study. Our results demonstrate strong evidence for an independent causal effect of smoking on oral/oropharyngeal cancer (IVW OR 2.6, 95% CI = 1.7, 3.9 per standard deviation increase in lifetime smoking behaviour) and an independent causal effect of alcohol consumption when controlling for smoking (IVW OR 2.1, 95% CI = 1.1, 3.8 per standard deviation increase in drinks consumed per week). This suggests the possibility that the causal effect of alcohol may have been underestimated. However, the extent to which alcohol is modified by smoking requires further investigation
- …