371 research outputs found
Pharmacokinetics and oral bioavailability of metformin hydrochloride in healthy mixed-breed dogs
Dialogue Design for a Robot-Based Face-Mirroring Game to Engage Autistic Children with Emotional Expressions
We present design strategies for Human Robot Interaction for school-aged autistic children with limited receptive language. Applying these strategies to the DE-ENIGMA project (large EU project addressing emotion recognition in autistic children) supported development of a new activity for in facial expression imitation whereby the robot imitates the child’s face to encourage the child to notice facial expressions in a play-based game. A usability case study with 15 typically-developing children aged 4–6 at an English-language school in the Netherlands was performed to observe the feasibility of the setup and make design revisions before exposing the robot to autistic children
HIV infection and cardiovascular disease in women
Background HIV infection is associated with increased risk of cardiovascular disease (CVD) in men. Whether HIV is an independent risk factor for CVD in women has not yet been established. Methods and Results We analyzed data from the Veterans Aging Cohort Study on 2187 women (32% HIV infected [HIV+]) who were free of CVD at baseline. Participants were followed from their first clinical encounter on or after April 01, 2003 until a CVD event, death, or the last follow‐up date (December 31, 2009). The primary outcome was CVD (acute myocardial infarction [AMI], unstable angina, ischemic stroke, and heart failure). CVD events were defined using clinical data, International Classification of Diseases, Ninth Revision, Clinical Modification codes, and/or death certificate data. We used Cox proportional hazards models to assess the association between HIV and incident CVD, adjusting for age, race/ethnicity, lipids, smoking, blood pressure, diabetes, renal disease, obesity, hepatitis C, and substance use/abuse. Median follow‐up time was 6.0 years. Mean age at baseline of HIV+ and HIV uninfected (HIV−) women was 44.0 versus 43.2 years (PP=0.11). There were 86 incident CVD events (53%, HIV+): AMI, 13%; unstable angina, 8%; ischemic stroke, 22%; and heart failure, 57%. Incident CVD/1000 person‐years was significantly higher among HIV+ (13.5; 95% confidence interval [CI]=10.1, 18.1) than HIV−women (5.3; 95% CI=3.9, 7.3; P+ women had an increased risk of CVD, compared to HIV− (hazard ratio=2.8; 95% CI=1.7, 4.6; P\u3c0.001). Conclusions HIV is associated with an increased risk of CVD in women
Towards a grapho-phonologically parsed corpus of medieval Scots:Database design and technical solutions
This paper presents a newly constructed corpus of sound-to-spelling mappings in medieval Scots, which stems from the work of the From Inglis to Scots (FITS) project. We have developed a systematic approach to the relationships between individual spellings and proposed sound values, and recorded these mutual links in a relational database. In this paper, we introduce the theoretical underpinnings of sound-to-spelling and spelling-to-sound mappings, and show how a Scots root morpheme undergoes grapho-phonological parsing, the analytical procedure that is employed to break down spelling sequences into sound units. We explain the data collection and annotation for the FITS Corpus (Alcorn et al., forthcoming), drawing attention to the extensive meta-data which accompany each analysed unit of spelling and sound. The database records grammatical and lexical information about the root, the positional arrangement of segments within the root, labels for the nuclei, vowels and consonants, the morphological context, and extra-linguistic detail of the text a given root was taken from (date, place and text type). With this wealth of information, the FITS corpus is capable of answering complex queries about the sound and spelling systems of medieval Scots. We also suggest how our methodology can be transferred to other non-standardised spelling systems
Lung epithelial protein disulfide isomerase A3 (PDIA3) plays an important role in influenza infection, inflammation, and airway mechanics
© 2019 Protein disulfide isomerases (PDI) are a family of redox chaperones that catalyze formation or isomerization of disulfide bonds in proteins. Previous studies have shown that one member, PDIA3, interacts with influenza A virus (IAV) hemagglutinin (HA), and this interaction is required for efficient oxidative folding of HA in vitro. However, it is unknown whether these host-viral protein interactions occur during active infection and whether such interactions represent a putative target for the treatment of influenza infection. Here we show that PDIA3 is specifically upregulated in IAV-infected mouse or human lung epithelial cells and PDIA3 directly interacts with IAV-HA. Treatment with a PDI inhibitor, LOC14 inhibited PDIA3 activity in lung epithelial cells, decreased intramolecular disulfide bonds and subsequent oligomerization (maturation) of HA in both H1N1 (A/PR8/34) and H3N2 (X31, A/Aichi/68) infected lung epithelial cells. These reduced disulfide bond formation significantly decreased viral burden, and also pro-inflammatory responses from lung epithelial cells. Lung epithelial-specific deletion of PDIA3 in mice resulted in a significant decrease in viral burden and lung inflammatory-immune markers upon IAV infection, as well as significantly improved airway mechanics. Taken together, these results indicate that PDIA3 is required for effective influenza pathogenesis in vivo, and pharmacological inhibition of PDIs represents a promising new anti-influenza therapeutic strategy during pandemic and severe influenza seasons
Temporal and Spatial Patterns of Ambient Endotoxin Concentrations in Fresno, California
BackgroundEndotoxins are found in indoor dust generated by human activity and pets, in soil, and adsorbed onto the surfaces of ambient combustion particles. Endotoxin concentrations have been associated with respiratory symptoms and the risk of atopy and asthma in children.ObjectiveWe characterized the temporal and spatial variability of ambient endotoxin in Fresno/Clovis, California, located in California's Central Valley, to identify correlates and potential predictors of ambient endotoxin concentrations in a cohort of children with asthma [Fresno Asthmatic Children's Environment Study (FACES)].MethodsBetween May 2001 and October 2004, daily ambient endotoxin and air pollutants were collected at the central ambient monitoring site of the California Air Resources Board in Fresno and, for shorter time periods, at 10 schools and indoors and outdoors at 84 residences in the community. Analyses were restricted to May-October, the dry months during which endotoxin concentrations are highest.ResultsDaily endotoxin concentration patterns were determined mainly by meteorologic factors, particularly the degree of air stagnation. Overall concentrations were lowest in areas distant from agricultural activities. Highest concentrations were found in areas immediately downwind from agricultural/pasture land. Among three other measured air pollutants [fine particulate matter, elemental carbon (a marker of traffic in Fresno), and coarse particulate matter (PMc)], PMc was the only pollutant correlated with endotoxin. Endotoxin, however, was the most spatially variable.ConclusionsOur data support the need to evaluate the spatial/temporal variability of endotoxin concentrations, rather than relying on a few measurements made at one location, in studies of exposure and and respiratory health effects, particularly in children with asthma and other chronic respiratory diseases
Differential Requirement for c-Jun N-terminal Kinase 1 in Lung Inflammation and Host Defense
The c-Jun N-terminal kinase (JNK) - 1 pathway has been implicated in the cellular response to stress in many tissues and models. JNK1 is known to play a role in a variety of signaling cascades, including those involved in lung disease pathogenesis. Recently, a role for JNK1 signaling in immune cell function has emerged. The goal of the present study was to determine the role of JNK1 in host defense against both bacterial and viral pneumonia, as well as the impact of JNK1 signaling on IL-17 mediated immunity. Wild type (WT) and JNK1 −/− mice were challenged with Escherichia coli, Staphylococcus aureus, or Influenza A. In addition, WT and JNK1 −/− mice and epithelial cells were stimulated with IL-17A. The impact of JNK1 deletion on pathogen clearance, inflammation, and histopathology was assessed. JNK1 was required for clearance of E. coli, inflammatory cell recruitment, and cytokine production. Interestingly, JNK1 deletion had only a small impact on the host response to S. aureus. JNK1 −/− mice had decreased Influenza A burden in viral pneumonia, yet displayed worsened morbidity. Finally, JNK1 was required for IL-17A mediated induction of inflammatory cytokines and antimicrobial peptides both in epithelial cells and the lung. These data identify JNK1 as an important signaling molecule in host defense and demonstrate a pathogen specific role in disease. Manipulation of the JNK1 pathway may represent a novel therapeutic target in pneumonia
Hard Photodisintegration of a Proton Pair
We present a study of high energy photodisintegration of proton-pairs through
the gamma + 3He -> p+p+n channel. Photon energies from 0.8 to 4.7 GeV were used
in kinematics corresponding to a proton pair with high relative momentum and a
neutron nearly at rest. The s-11 scaling of the cross section, as predicted by
the constituent counting rule for two nucleon photodisintegration, was observed
for the first time. The onset of the scaling is at a higher energy and the
cross section is significantly lower than for deuteron (pn pair)
photodisintegration. For photon energies below the scaling region, the scaled
cross section was found to present a strong energy-dependent structure not
observed in deuteron photodisintegration.Comment: 7 pages, 3 figures, for submission to Phys. Lett.
Radiographers supporting radiologists in the interpretation of screening mammography: a viable strategy to meet the shortage in the number of radiologists.
BackgroundAn alternative approach to the traditional model of radiologists interpreting screening mammography is necessary due to the shortage of radiologists to interpret screening mammograms in many countries.MethodsWe evaluated the performance of 15 Mexican radiographers, also known as radiologic technologists, in the interpretation of screening mammography after a 6 months training period in a screening setting. Fifteen radiographers received 6 months standardized training with radiologists in the interpretation of screening mammography using the Breast Imaging Reporting and Data System (BI-RADS) system. A challenging test set of 110 cases developed by the Breast Cancer Surveillance Consortium was used to evaluate their performance. We estimated sensitivity, specificity, false positive rates, likelihood ratio of a positive test (LR+) and the area under the subject-specific Receiver Operating Characteristic (ROC) curve (AUC) for diagnostic accuracy. A mathematical model simulating the consequences in costs and performance of two hypothetical scenarios compared to the status quo in which a radiologist reads all screening mammograms was also performed.ResultsRadiographer's sensitivity was comparable to the sensitivity scores achieved by U.S. radiologists who took the test but their false-positive rate was higher. Median sensitivity was 73.3 % (Interquartile range, IQR: 46.7-86.7 %) and the median false positive rate was 49.5 % (IQR: 34.7-57.9 %). The median LR+ was 1.4 (IQR: 1.3-1.7 %) and the median AUC was 0.6 (IQR: 0.6-0.7). A scenario in which a radiographer reads all mammograms first, and a radiologist reads only those that were difficult for the radiographer, was more cost-effective than a scenario in which either the radiographer or radiologist reads all mammograms.ConclusionsGiven the comparable sensitivity achieved by Mexican radiographers and U.S. radiologists on a test set, screening mammography interpretation by radiographers appears to be a possible adjunct to radiologists in countries with shortages of radiologists. Further studies are required to assess the effectiveness of different training programs in order to obtain acceptable screening accuracy, as well as the best approaches for the use of non-physician readers to interpret screening mammography
The lead-glass electromagnetic calorimeters for the magnetic spectrometers in Hall C at Jefferson Lab
The electromagnetic calorimeters of the various magnetic spectrometers in
Hall C at Jefferson Lab are presented. For the existing HMS and SOS
spectrometers design considerations, relevant construction information, and
comparisons of simulated and experimental results are included. The energy
resolution of the HMS and SOS calorimeters is better than , and pion/electron () separation of about 100:1 has been
achieved in energy range 1 -- 5 GeV. Good agreement has been observed between
the experimental and simulated energy resolutions, but simulations
systematically exceed experimentally determined suppression factors by
close to a factor of two. For the SHMS spectrometer presently under
construction details on the design and accompanying GEANT4 simulation efforts
are given. The anticipated performance of the new calorimeter is predicted over
the full momentum range of the SHMS. Good electron/hadron separation is
anticipated by combining the energy deposited in an initial (preshower)
calorimeter layer with the total energy deposited in the calorimeter.Comment: 22 pages, 33 figure
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