Prenatal arachidonic acid exposure and selected immune-related variables in childhood

Arachidonic acid (AA) is considered essential in fetal development and some of its metabolites are thought to be important mediators of the immune responses. Therefore, we studied whether prenatal exposure to AA is associated with some immune-related clinical conditions and plasma markers in childhood. In 280 children aged 7 years, atopy, lung function and plasma inflammation markers were measured and their relationships with early AA exposure were studied by linear and logistic regression analyses. AA exposure was deduced from AA concentrations in plasma phospholipids of the mothers collected at several time points during pregnancy and at delivery, and in umbilical cord plasma and arterial and venous wall phospholipids. In unadjusted regression analyses, significant positive associations were observed between maternal AA concentrations at 16 and 32 weeks of pregnancy (proxies for fetal AA exposure) and peak expiratory flow decline after maximal physical exercise and plasma fibrinogen concentrations of their children, respectively. However, after correction for relevant covariables, only trends remained. A significant negative relationship was observed between AA concentrations in cord plasma (reflecting prenatal AA exposure) and the average daily amplitude of peak expiratory flow at rest, which lost significance after appropriate adjustment. Because of these few, weak and inconsistent relationships, a major impact of early-life exposure to AA on atopy, lung function and selected plasma inflammation markers of children at 7 years of age seems unlikely

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Abstract The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared to information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known non-pathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification. This article is protected by copyright. All rights reserved.Peer reviewe

Growth of nanodroplets on a still microfiber under flow conditions

Surface droplets in the microscale are of great interest for their relevance in broad droplet-based technologies. Derived from the Ouzo effect, the solvent exchange process is a simple bottom-up approach to produce surface nano-/micro-droplets by the nucleation and growth mechanism. The oil oversaturation pulse is created as a good solvent (ethanol) for the oil displaced by a poor solvent (water) in the flow cell. In this work, we investigated the formation of surface droplets on a one-dimensional substrate (a single hydrophobic fiber with a diameter of 10 μm) in a flow. The droplet growth on the microfiber is enhanced as the fiber is perpendicular to the external flow direction, due to the coupled effects between the droplet formation and the local flow. On the other hand, the droplet growth exhibits different growth dynamics when the fiber is placed parallel to the external flow direction. The general trend that surface droplets grow faster on a fiber at higher flow rates is consistent with the situation on planar substrates. The coupled interactions between the growing droplets and the local flow conditions during the solvent exchange process were further revealed in the simulations. The findings from this work will be valuable for the design and utilization of the solvent exchange process to produce surface nanodroplets on a microfiber under flow conditions and thus broaden the droplet-based application fields

Vorticity-induced flow-focusing leads to bubble entrainment in an inkjet printhead: Synchrotron x-ray and volume-of-fluid visualizations

The oscillatory flows present in an inkjet printhead can lead to strong deformations of the air-liquid interface at the nozzle exit. Such deformations may lead to an inward directed air jet with bubble pinch-off and the subsequent entrainment of an air bubble, which is highly detrimental to the stability of inkjet printing. Understanding the mechanisms of bubble entrainment is therefore crucial to improving print stability. In the present work, we use ultrafast x-ray phase-contrast imaging and direct numerical simulations based on the volume-of-fluid method to study the mechanisms underlying the bubble entrainment in a piezoacoustic printhead. We first demonstrate good agreement between experiments and numerics. We then show the different classes of bubble pinch-off obtained in experiments, and that those were also captured numerically. The numerical results are then used to show that the baroclinic torque, which is generated at the gas-liquid interface due to the misalignment of density and pressure gradients, results in a flow-focusing effect that drives the formation of the air jet from which a bubble can pinch off

Vorticity-induced flow-focusing leads to bubble entrainment in an inkjet printhead: synchrotron X-ray and volume-of-fluid visualizations

The oscillatory flows present in an inkjet printhead can lead to strong deformations of the air-liquid interface at the nozzle exit. Such deformations may lead to an inward directed air jet with bubble pinch-off and the subsequent entrainment of an air bubble, which is highly detrimental to the stability of inkjet printing. Understanding the mechanisms of bubble entrainment is therefore crucial in improving print stability. In the present work, we use ultrafast X-ray phase-contrast imaging and direct numerical simulations based on the Volume-of-Fluid method to study the mechanisms underlying the bubble entrainment in a piezo-acoustic printhead. We first demonstrate good agreement between experiments and numerics. We then show the different classes of bubble pinch-off obtained in experiments, and that those were also captured numerically. The numerical results are then used to show that the baroclinic torque, which is generated at the gas-liquid interface due to the misalignment of density and pressure gradients, results in a flow-focusing effect that drives the formation of the air jet from which a bubble can pinch-off.Comment: For supplementary movies, visit: https://www.youtube.com/playlist?list=PLmU3YKXYzq7oEm9qKD9bL_eWKSNP3uGt

Drop impact on hot plates: contact times, lift-off and the lamella rupture

When a liquid drop impacts on a heated substrate, it can remain deposited, or violently boil in contact, or lift off with or without ever touching the surface. The latter is known as the Leidenfrost effect. The duration and area of the liquid-substrate contact are highly relevant for the heat transfer, as well as other effects such as corrosion. However, most experimental studies rely on side view imaging to determine contact times, and those are often mixed with the time until the drop lifts off from the substrate. Here, we develop and validate a reliable method of contact time determination using high-speed X-ray imaging and total internal reflection imaging. We exemplarily compare contact and lift-off times on flat silicon and sapphire substrates. We show that drops can rebound even without formation of a complete vapor layer, with a wide range of lift-off times. On sapphire, we find a local minimum of lift-off times that is much shorter than expected from capillary rebound in the comparatively low-temperature regime of transition boiling/thermal atomization. We elucidate the underlying mechanism related to spontaneous rupture of the lamella and receding of the contact area.11Nsciescopu

Disturbing bubbles in drop-on-demand piezo-acoustic inkjet printing

Drop-on-demand piezo-acoustic inkjet printing is the method of choice for high-frequency and high-precision droplet deposition. Microbubbles entrained in a piezo-driven silicon MEMS printhead disturb the acoustics of the microfluidic ink channel and, thereby, the jetting behavior. The strong deformations of the air-liquid interface at the nozzle exit may lead to an inward directed air jet with bubble pinch-off and the subsequent entrainment of an air bubble. Here, we use ultrafast x-ray phase-contrast imaging and direct numerical simulations to study the mechanisms underlying the bubble entrainment, where we demonstrate good agreement between experiments and numerics. The entrained bubbles were also visualized in the ink channel of the silicon printhead in a highly sensitive shortwave infrared (SWIR) imaging setup exploiting the optical window at 1550 nm. The infrared recordings show the rich phenomena of acoustically driven bubble dynamics inside the printhead. We also study the resonance behavior of the ink channel as a function of the microbubble size and number of bubbles through theoretical modeling and experiments. The system is modeled as a set of two coupled harmonic oscillators, one for the compliant ink channel and one for the microbubble and where we find excellent agreement between the predicted and measured eigenfrequencies

Downward jetting of a dynamic Leidenfrost drop

Jetting is a universal phenomenon frequently observed in nature and industries, for instance, in rain drop impact, inkjet printing, spray cooling, fuel atomization, etc. In drop impact on a superheated surface, we observe the formation of a vapor cavity beneath the dynamic Leidenfrost drop and a consecutive downward ejection of a jet into the cavity using ultrafast x-ray phase contrast imaging. We reveal that the cavity is induced mostly by the retraction of the drop and the jetting is caused by the convergence of capillary waves along the liquid-cavity interface. We find a jetting criterion based on the viscous damping of capillary waves: [OhWe(2)] <= 66 +/- 10. These results can provide important insight that leads to understanding and modeling of jets in nature.11Nsciescopu