827 research outputs found
Reconstruction of Random Colourings
Reconstruction problems have been studied in a number of contexts including
biology, information theory and and statistical physics. We consider the
reconstruction problem for random -colourings on the -ary tree for
large . Bhatnagar et. al. showed non-reconstruction when and reconstruction when . We tighten this result and show non-reconstruction when and reconstruction when .Comment: Added references, updated notatio
Human carbonic anhydrase IV: cDNA cloning, sequence comparison, and expression in COS cell membranes.
The role of intermediate vesicles in the adsorptive endocytosis and transport of ligand to lysosomes by human fibroblasts.
Severity and persistence of asthma and mental health: a birth cohort study
Background. The goal of the current study was to investigate asthma and mental health among youth in the community, and to consider the role of asthma severity and persistence in this link
Cord blood group 2 innate lymphoid cells are associated with lung function at 6 weeks of age.
Objective: Offspring born to mothers with asthma in pregnancy are known to have lower lung function which tracks with age. Human group 2 innate lymphoid cells (ILC2) accumulate in foetal lungs, at 10-fold higher levels compared to adult lungs. However, there are no data on foetal ILC2 numbers and the association with respiratory health outcomes such as lung function in early life. We aimed to investigate cord blood immune cell populations from babies born to mothers with asthma in pregnancy. Methods: Cord blood from babies born to asthmatic mothers was collected, and cells were stained in whole cord blood. Analyses were done using traditional gating approaches and computational methodologies (t-distributed stochastic neighbour embedding and PhenoGraph algorithms). At 6 weeks of age, the time to peak tidal expiratory flow as a percentage of total expiratory flow time (tPTEF/tE%) was determined as well as Lung Clearance Index (LCI), during quiet natural sleep. Results: Of 110 eligible infants (March 2017 to November 2019), 91 were successfully immunophenotyped (82.7%). Lung function was attempted in 61 infants (67.0%), and 43 of those infants (70.5% of attempted) had technically acceptable tPTEF/tE% measurements. Thirty-four infants (55.7% of attempted) had acceptable LCI measurements. Foetal ILC2 numbers with increased expression of chemoattractant receptor-homologous molecule (CRTh2), characterised by two distinct analysis methodologies, were associated with poorer infant lung function at 6 weeks of age." Conclusion: Foetal immune responses may be a surrogate variable for or directly influence lung function outcomes in early life
A screening tool to identify risk for bronchiectasis progression in children with cystic fibrosis
BACKGROUND: The marked heterogeneity in cystic fibrosis (CF) disease complicates the selection of those most likely to benefit from existing or emergent treatments. OBJECTIVE: We aimed to predict the progression of bronchiectasis in preschool children with CF. METHODS: Using data collected up to 3 years of age, in the Australian Respiratory Early Surveillance Team for CF cohort study, clinical information, chest computed tomography (CT) scores, and biomarkers from bronchoalveolar lavage were assessed in a multivariable linear regression model as predictors for CT bronchiectasis at age 5–6. RESULTS: Follow‐up at 5–6 years was available in 171 children. Bronchiectasis prevalence at 5–6 was 134/171 (78%) and median bronchiectasis score was 3 (range 0–12). The internally validated multivariate model retained eight independent predictors accounting for 37% (adjusted R (2)) of the variance in bronchiectasis score. The strongest predictors of future bronchiectasis were: pancreatic insufficiency, repeated intravenous treatment courses, recurrent lower respiratory infections in the first 3 years of life, and lower airway inflammation. Dichotomizing the resulting prediction score at a bronchiectasis score of above the median resulted in a diagnostic odds ratio of 13 (95% confidence interval [CI], 6.3–27) with positive and negative predictive values of 80% (95% CI, 72%–86%) and 77% (95% CI, 69%–83%), respectively. CONCLUSION: Early assessment of bronchiectasis risk in children with CF is feasible with reasonable precision at a group level, which can assist in high‐risk patient selection for interventional trials. The unexplained variability in disease progression at individual patient levels remains high, limiting the use of this model as a clinical prediction tool
Evaluation of combined live, attenuated respiratory syncytial virus and parainfluenza 3 virus vaccines in infants and young children
© 2004 by the Infectious Diseases Society of America. All rights reserved.We evaluated a combination respiratory syncytial virus (RSV) and parainfluenza 3 virus (PIV3) live, attenuated intranasal vaccine for safety, viral replication, and immunogenicity in doubly seronegative children 6–18 months old. RSV cpts-248/404 and PIV3-cp45 vaccines were combined in a dose of 105 plaque-forming units of each per 0.5-mL dose and compared with monovalent vaccines or placebo. The virus shedding pattern of RSV was not different between monovalent RSV cpts-248/404 vaccine and combination vaccine. Modest reductions in the shedding of PIV3-cp45 vaccine virus were found after the administration of RSV cpts-248/404 and PIV3-cp45 vaccine, relative to monovalent PIV3 vaccine; 16 (76%) of 21 children given combination vaccine shed PIV3-cp45 versus 11 (92%) of 12 of those given monovalent PIV3 vaccine. Both vaccines were immunogenic, and antibody responses were similar between the monovalent groups and the combination group. Combined RSV/PV3 vaccine is feasible for simultaneous administration, and further studies are warranted.Robert B. Belshe, Frances K. Newman, Edwin L. Anderson, Peter F. Wright, Ruth A. Karron,Sharon Tollefson, Frederick W. Henderson, H. Cody Meissner, Shabir Madhi, Don Roberton, Helen Marshall,Richard Loh, Peter Sly, Brian Murphy, Joanne M. Tatem, Valerie Randolph, Jill Hackell, William Gruber and Theodore F. Tsa
Constitutive Activation of the Src Family Kinase Hck Results in Spontaneous Pulmonary Inflammation and an Enhanced Innate Immune Response
To identify the physiological role of Hck, a functionally redundant member of the Src family of tyrosine kinases expressed in myelomonocytic cells, we generated HckF/F “knock-in” mice which carry a targeted tyrosine (Y) to phenylalanine (F) substitution of the COOH-terminal, negative regulatory Y499-residue in the Hck protein. Unlike their Hck−/− “loss-of-function” counterparts, HckF/F “gain-of-function” mice spontaneously acquired a lung pathology characterized by extensive eosinophilic and mononuclear cell infiltration within the lung parenchyma, alveolar airspaces, and around blood vessels, as well as marked epithelial mucus metaplasia in conducting airways. Lungs from HckF/F mice showed areas of mild emphysema and pulmonary fibrosis, which together with inflammation resulted in altered lung function and respiratory distress in aging mice. When challenged transnasally with lipopolysaccharide (LPS), HckF/F mice displayed an exaggerated pulmonary innate immune response, characterized by excessive release of matrix metalloproteinases and tumor necrosis factor (TNF)α. Similarly, HckF/F mice were highly sensitive to endotoxemia after systemic administration of LPS, and macrophages and neutrophils derived from HckF/F mice exhibited enhanced effector functions in vitro (e.g., nitric oxide and TNFα production, chemotaxis, and degranulation). Based on the demonstrated functional association of Hck with leukocyte integrins, we propose that constitutive activation of Hck may mimic adhesion-dependent priming of leukocytes. Thus, our observations collectively suggest an enhanced innate immune response in HckF/F mice thereby skewing innate immunity from a reversible physiological host defense response to one causing irreversible tissue damage
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