237 research outputs found
Renormalization of correlations in a quasiperiodically forced two-level system for a general class of modulation function
Determination of Inter-Phase Line Tension in Langmuir Films
A Langmuir film is a molecularly thin film on the surface of a fluid; we
study the evolution of a Langmuir film with two co-existing fluid phases driven
by an inter-phase line tension and damped by the viscous drag of the underlying
subfluid. Experimentally, we study an 8CB Langmuir film via digitally-imaged
Brewster Angle Microscopy (BAM) in a four-roll mill setup which applies a
transient strain and images the response. When a compact domain is stretched by
the imposed strain, it first assumes a bola shape with two tear-drop shaped
reservoirs connected by a thin tether which then slowly relaxes to a circular
domain which minimizes the interfacial energy of the system. We process the
digital images of the experiment to extract the domain shapes. We then use one
of these shapes as an initial condition for the numerical solution of a
boundary-integral model of the underlying hydrodynamics and compare the
subsequent images of the experiment to the numerical simulation. The numerical
evolutions first verify that our hydrodynamical model can reproduce the
observed dynamics. They also allow us to deduce the magnitude of the line
tension in the system, often to within 1%. We find line tensions in the range
of 200-600 pN; we hypothesize that this variation is due to differences in the
layer depths of the 8CB fluid phases.Comment: See (http://www.math.hmc.edu/~ajb/bola/) for related movie
Common carotid intima media thickness and ankle-brachial pressure index correlate with local but not global atheroma burden:a cross sectional study using whole body magnetic resonance angiography
Common carotid intima media thickness (CIMT) and ankle brachial pressure index (ABPI) are used as surrogate marker of atherosclerosis, and have been shown to correlate with arterial stiffness, however their correlation with global atherosclerotic burden has not been previously assessed. We compare CIMT and ABPI with atheroma burden as measured by whole body magnetic resonance angiography (WB-MRA).50 patients with symptomatic peripheral arterial disease were recruited. CIMT was measured using ultrasound while rest and exercise ABPI were performed. WB-MRA was performed in a 1.5T MRI scanner using 4 volume acquisitions with a divided dose of intravenous gadolinium gadoterate meglumine (Dotarem, Guerbet, FR). The WB-MRA data was divided into 31 anatomical arterial segments with each scored according to degree of luminal narrowing: 0 = normal, 1 = <50%, 2 = 50-70%, 3 = 70-99%, 4 = vessel occlusion. The segment scores were summed and from this a standardized atheroma score was calculated.The atherosclerotic burden was high with a standardised atheroma score of 39.5±11. Common CIMT showed a positive correlation with the whole body atheroma score (β 0.32, p = 0.045), however this was due to its strong correlation with the neck and thoracic segments (β 0.42 p = 0.01) with no correlation with the rest of the body. ABPI correlated with the whole body atheroma score (β -0.39, p = 0.012), which was due to a strong correlation with the ilio-femoral vessels with no correlation with the thoracic or neck vessels. On multiple linear regression, no correlation between CIMT and global atheroma burden was present (β 0.13 p = 0.45), while the correlation between ABPI and atheroma burden persisted (β -0.45 p = 0.005).ABPI but not CIMT correlates with global atheroma burden as measured by whole body contrast enhanced magnetic resonance angiography in a population with symptomatic peripheral arterial disease. However this is primarily due to a strong correlation with ilio-femoral atheroma burden
A Multiplexed Single-Cell CRISPR Screening Platform Enables Systematic Dissection of the Unfolded Protein Response
Functional genomics efforts face tradeoffs between number of perturbations examined and complexity of phenotypes measured. We bridge this gap with Perturb-seq, which combines droplet-based single-cell RNA-seq with a strategy for barcoding CRISPR-mediated perturbations, allowing many perturbations to be profiled in pooled format. We applied Perturb-seq to dissect the mammalian unfolded protein response (UPR) using single and combinatorial CRISPR perturbations. Two genome-scale CRISPR interference (CRISPRi) screens identified genes whose repression perturbs ER homeostasis. Subjecting ∼100 hits to Perturb-seq enabled high-precision functional clustering of genes. Single-cell analyses decoupled the three UPR branches, revealed bifurcated UPR branch activation among cells subject to the same perturbation, and uncovered differential activation of the branches across hits, including an isolated feedback loop between the translocon and IRE1α. These studies provide insight into how the three sensors of ER homeostasis monitor distinct types of stress and highlight the ability of Perturb-seq to dissect complex cellular responses.National Human Genome Research Institute (U.S.) (Grant P50HG006193
Cardiac mitochondrial function depends on BUD23 mediated ribosome programming.
Efficient mitochondrial function is required in tissues with high energy demand such as the heart, and mitochondrial dysfunction is associated with cardiovascular disease. Expression of mitochondrial proteins is tightly regulated in response to internal and external stimuli. Here we identify a novel mechanism regulating mitochondrial content and function, through BUD23-dependent ribosome generation. BUD23 was required for ribosome maturation, normal 18S/28S stoichiometry and modulated the translation of mitochondrial transcripts in human A549 cells. Deletion of Bud23 in murine cardiomyocytes reduced mitochondrial content and function, leading to severe cardiomyopathy and death. We discovered that BUD23 selectively promotes ribosomal interaction with low GC-content 5'UTRs. Taken together we identify a critical role for BUD23 in bioenergetics gene expression, by promoting efficient translation of mRNA transcripts with low 5'UTR GC content. BUD23 emerges as essential to mouse development, and to postnatal cardiac function
Perinatal paracetamol exposure in mice does not affect the development of allergic airways disease in early life
Background Current data concerning maternal paracetamol intake during pregnancy, or intake during infancy and risk of wheezing or asthma in childhood is inconclusive based on epidemiological studies. We have investigated whether there is a causal link between maternal paracetamol intake during pregnancy and lactation and the development of house dust mite (HDM) induced allergic airways disease (AAD) in offspring using a neonatal mouse model.
Methods Pregnant mice were administered paracetamol or saline by oral gavage from the day of mating throughout pregnancy and/or lactation. Subsequently, their pups were exposed to intranasal HDM or saline from day 3 of life for up to 6 weeks. Assessments of airway hyper-responsiveness, inflammation and remodelling were made at weaning (3 weeks) and 6 weeks of age.
Results Maternal paracetamol exposure either during pregnancy and/or lactation did not affect development of AAD in offspring at weaning or at 6 weeks. There were no effects of maternal paracetamol at any time point on airway remodelling or IgE levels.
Conclusions Maternal paracetamol did not enhance HDM induced AAD in offspring. Our mechanistic data do not support the hypothesis that prenatal paracetamol exposure increases the risk of childhood asthma
Costa Rica Rift hole deepened and logged
During Leg 111 of the Ocean Drilling
Program, scientists on the
drilling vessel JOIDES Resolution
studied crustal structure and hydrothermal
processes in the eastern
equatorial Pacific. Leg 111 spent 43
days on its primary objective, deepening
and logging Hole 5048, a deep
reference hole in 5.9-million-year-old
crust 200 km south of the spreading
axis of the Costa Rica Rift. Even before
Leg 111 , Hole 5048 was the deepest
hole drilled into the oceanic crust,
penetrating 274.5 m of sediments and
1,075.5 m of pillow lavas and sheeted
dikes to a total depth of 1,350 m
below sea floor (mbsf). Leg 111 deepened
the hole by 212.3 m to a total
depth of 1,562.3 mbsf (1,287.8 m into
basement), and completed a highly successful suite of geophysical logs
and experiments, including sampling
of borehole waters
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