Fluids with spatial density variations of single or mixed molecules play a key role in biophysics, soft matter, and materials science. The fluid structures usually form via spinodal decomposition or ...nucleation following an instantaneous destabilization of the initially disordered fluid. However, in practice, an instantaneous quench is often not viable, and the rate of destabilization may be gradual rather than instantaneous. In this work we show that the commonly used phenomenological descriptions of fluid structuring are inadequate under these conditions. We come to that conclusion in the context of surface catalysis, where we employ kinetic Monte Carlo simulations to describe the unimolecular adsorption of gaseous molecules onto a metal surface. The adsorbates diffuse at the surface and, as a consequence of lateral interactions and due to an ongoing increase of the surface coverage, phase separate into coexisting low- and high-density regions. The typical size of these regions turns out to depend much more strongly on the rate of adsorption than predicted from recently reported phenomenological models. We discuss how this finding contributes to the fundamental understanding of the crossover from liquid-liquid to liquid-solid demixing of solution-cast polymer blends.
Context. Future large-scale surveys with high-resolution imaging will provide us with approximately 105 new strong galaxy-scale lenses. These strong-lensing systems will be contained in large data ...amounts, however, which are beyond the capacity of human experts to visually classify in an unbiased way. Aims. We present a new strong gravitational lens finder based on convolutional neural networks (CNNs). The method was applied to the strong-lensing challenge organized by the Bologna Lens Factory. It achieved first and third place, respectively, on the space-based data set and the ground-based data set. The goal was to find a fully automated lens finder for ground-based and space-based surveys that minimizes human inspection. Methods. We compared the results of our CNN architecture and three new variations (“invariant” “views” and “residual”) on the simulated data of the challenge. Each method was trained separately five times on 17 000 simulated images, cross-validated using 3000 images, and then applied to a test set with 100 000 images. We used two different metrics for evaluation, the area under the receiver operating characteristic curve (AUC) score, and the recall with no false positive (Recall0FP). Results. For ground-based data, our best method achieved an AUC score of 0.977 and a Recall0FP of 0.50. For space-based data, our best method achieved an AUC score of 0.940 and a Recall0FP of 0.32. Adding dihedral invariance to the CNN architecture diminished the overall score on space-based data, but achieved a higher no-contamination recall. We found that using committees of five CNNs produced the best recall at zero contamination and consistently scored better AUC than a single CNN. Conclusions. We found that for every variation of our CNN lensfinder, we achieved AUC scores close to 1 within 6%. A deeper network did not outperform simpler CNN models either. This indicates that more complex networks are not needed to model the simulated lenses. To verify this, more realistic lens simulations with more lens-like structures (spiral galaxies or ring galaxies) are needed to compare the performance of deeper and shallower networks.
Alcohol consumption is a complex trait determined by both genetic and environmental factors, and is correlated with the risk of alcohol use disorders. Although a small number of genetic loci have ...been reported to be associated with variation in alcohol consumption, genetic factors are estimated to explain about half of the variance in alcohol consumption, suggesting that additional loci remain to be discovered. We conducted a genome-wide association study (GWAS) of alcohol consumption in the large Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort, in four race/ethnicity groups: non-Hispanic whites, Hispanic/Latinos, East Asians and African Americans. We examined two statistically independent phenotypes reflecting subjects' alcohol consumption during the past year, based on self-reported information: any alcohol intake (drinker/non-drinker status) and the regular quantity of drinks consumed per week (drinks/week) among drinkers. We assessed these two alcohol consumption phenotypes in each race/ethnicity group, and in a combined trans-ethnic meta-analysis comprising a total of 86 627 individuals. We observed the strongest association between the previously reported single nucleotide polymorphism (SNP) rs671 in ALDH2 and alcohol drinker status (odd ratio (OR)=0.40, P=2.28 × 10
) in East Asians, and also an effect on drinks/week (beta=-0.17, P=5.42 × 10
) in the same group. We also observed a genome-wide significant association in non-Hispanic whites between the previously reported SNP rs1229984 in ADH1B and both alcohol consumption phenotypes (OR=0.79, P=2.47 × 10
for drinker status and beta=-0.19, P=1.91 × 10
for drinks/week), which replicated in Hispanic/Latinos (OR=0.72, P=4.35 × 10
and beta=-0.21, P=2.58 × 10
, respectively). Although prior studies reported effects of ADH1B and ALDH2 on lifetime measures, such as risk of alcohol dependence, our study adds further evidence of the effect of the same genes on a cross-sectional measure of average drinking. Our trans-ethnic meta-analysis confirmed recent findings implicating the KLB and GCKR loci in alcohol consumption, with strongest associations observed for rs7686419 (beta=-0.04, P=3.41 × 10
for drinks/week and OR=0.96, P=4.08 × 10
for drinker status), and rs4665985 (beta=0.04, P=2.26 × 10
for drinks/week and OR=1.04, P=5 × 10
for drinker status), respectively. Finally, we also obtained confirmatory results extending previous findings implicating AUTS2, SGOL1 and SERPINC1 genes in alcohol consumption traits in non-Hispanic whites.
Cell death plays a critical role in inflammatory responses. During pyroptosis, inflammatory caspases cleave Gasdermin D (GSDMD) to release an N-terminal fragment that generates plasma membrane pores ...that mediate cell lysis and IL-1 cytokine release. Terminal cell lysis and IL-1β release following caspase activation can be uncoupled in certain cell types or in response to particular stimuli, a state termed hyperactivation. However, the factors and mechanisms that regulate terminal cell lysis downstream of GSDMD cleavage remain poorly understood. In the course of studies to define regulation of pyroptosis during Yersinia infection, we identified a line of Card19-deficient mice (Card19lxcn) whose macrophages were protected from cell lysis and showed reduced apoptosis and pyroptosis, yet had wild-type levels of caspase activation, IL-1 secretion, and GSDMD cleavage. Unexpectedly, CARD19, a mitochondrial CARD-containing protein, was not directly responsible for this, as an independently-generated CRISPR/Cas9 Card19 knockout mouse line (Card19Null) showed no defect in macrophage cell lysis. Notably, Card19 is located on chromosome 13, immediately adjacent to Ninj1, which was recently found to regulate cell lysis downstream of GSDMD activation. RNA-seq and western blotting revealed that Card19lxcn BMDMs have significantly reduced NINJ1 expression, and reconstitution of Ninj1 in Card19lxcn immortalized BMDMs restored their ability to undergo cell lysis in response to caspase-dependent cell death stimuli. Card19lxcn mice exhibited increased susceptibility to Yersinia infection, whereas independently-generated Card19Null mice did not, demonstrating that cell lysis itself plays a key role in protection against bacterial infection, and that the increased infection susceptibility of Card19lxcn mice is attributable to loss of NINJ1. Our findings identify genetic targeting of Card19 being responsible for off-target effects on the adjacent gene Ninj1, disrupting the ability of macrophages to undergo plasma membrane rupture downstream of gasdermin cleavage and impacting host survival and bacterial control during Yersinia infection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We investigate the rheological characteristics of human blood plasma in shear and elongational flows. While we can confirm a Newtonian behavior in shear flow within experimental resolution, we find a ...viscoelastic behavior of blood plasma in the pure extensional flow of a capillary breakup rheometer. The influence of the viscoelasticity of blood plasma on capillary blood flow is tested in a microfluidic device with a contraction-expansion geometry. Differential pressure measurements revealed that the plasma has a pronounced flow resistance compared to that of pure water. Supplementary measurements indicate that the viscoelasticity of the plasma might even lead to viscoelastic instabilities under certain conditions. Our findings show that the viscoelastic properties of plasma should not be ignored in future studies on blood flow.
The adaptor protein Bcl10 is a critically important mediator of T cell receptor (TCR)-to-NF-κB signaling. Bcl10 degradation is a poorly understood biological phenomenon suggested to reduce TCR ...activation of NF-κB. Here we have shown that TCR engagement triggers the degradation of Bcl10 in primary effector T cells but not in naive T cells. TCR engagement promoted K63 polyubiquitination of Bcl10, causing Bcl10 association with the autophagy adaptor p62. Paradoxically, p62 binding was required for both Bcl10 signaling to NF-κB and gradual degradation of Bcl10 by autophagy. Bcl10 autophagy was highly selective, as shown by the fact that it spared Malt1, a direct Bcl10 binding partner. Blockade of Bcl10 autophagy enhanced TCR activation of NF-κB. Together, these data demonstrate that selective autophagy of Bcl10 is a pathway-intrinsic homeostatic mechanism that modulates TCR signaling to NF-κB in effector T cells. This homeostatic process may protect T cells from adverse consequences of unrestrained NF-κB activation, such as cellular senescence.
Display omitted
► TCR-dependent Bcl10 degradation occurs in effector T cells but not naive T cells ► Bcl10 is degraded via TCR-dependent selective autophagy ► p62 is a key mediator of NF-κB activation and Bcl10 autophagy ► Selective autophagy of Bcl10 limits TCR activation of NF-κB
We theoretically study the impact of solvent evaporation on the dynamics of isothermal phase separation of ternary polymer solutions in thin films. In the early stages we obtain a spinodal length ...scale that decreases with time under the influence of ongoing evaporation. After that rapid demixing occurs at a well-defined lag time, a morphology emerges of which the compositions of the coexisting phases rapidly approach the binodal values. We find that the type of morphology, which can be either bicontinuous or dispersed, strongly depends on the evaporation rate if the solubility of the two solutes in the common solvent differs. We derive expressions that relate both the lag time and length scale characterizing the emerging morphology to all relevant physical parameters. These include the tracer diffusivities, the interaction parameters, the degrees of polymerization, the blend composition, and the evaporation rate. In agreement with our numerical results, we find the latter to scale with a one-sixth power of the evaporation rate. Following the lag time, a new length scale appears that increases with time due to coarsening. If evaporation is sufficiently slow, this length increases with the conventional one-third power of time. For rapid evaporation deviations from that may occur, especially if the solvent compatibility of the solutes differ. Our model calculations suggest that the characteristic features of the final dry-film morphology is dictated by the quench depth as well as the time available for coarsening, which are both determined by the rate of evaporation.
Background:
Air embolism (AE), especially when affecting the brain, is an underrated and potentially life-threatening complication in various endovascular interventions. This study aims to ...investigate experimental AEs using a new model to generate micro air bubbles (MAB), to assess the impact of a catheter on these MAB, and to demonstrate the applicability of this model in vivo.
Materials and Methods:
Micro air bubbles were created using a system based on microfluidic channels. The MAB were detected and analyzed automatically. Micro air bubbles, with a target size of 85 µm, were generated and injected through a microcatheter. The MAB diameters proximal and distal to the catheter were assessed and compared. In a subsequent in vivo application, 2000 MAB were injected into the aorta (at the aortic valve) and into the common carotid artery (CCA) of a rat, respectively, using a microcatheter, resembling AE occurring during cardiovascular interventions.
Results:
Micro air bubbles with a highly calibrated size could be successfully generated (median: 85.5 µm, SD 1.9 µm). After passage of the microcatheter, the MAB were similar in diameter (median: 86.6 µm) but at a lower number (60.1% of the injected MAB) and a substantially higher scattering of diameters (SD 29.6 µm). In vivo injection of MAB into the aorta resulted in cerebral microinfarctions in both hemispheres, whereas injection into the CCA caused exclusively ipsilateral microinfarctions.
Conclusion:
Using this new AE model, MAB can be generated precisely and reproducibly, resulting in cerebral microinfarctions. This model is feasible for further studies on the pathophysiology and prevention of AE in cardiovascular procedures.
The first‐line treatment of hyperuricemia, which causes gout, is allopurinol. The allopurinol response is highly variable, with many users failing to achieve target serum uric acid (SUA) levels. No ...genome‐wide association study (GWAS) has examined the genetic factors affecting allopurinol effectiveness. Using 2,027 subjects in Kaiser Permanente's Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort, we conducted a GWAS of allopurinol‐related SUA reduction, first in the largest ethnic group, non‐Hispanic white (NHW) subjects, and then in a stratified transethnic meta‐analysis. ABCG2, encoding the efflux pump BCRP, was associated with SUA reduction in NHW subjects (P = 2 × 10−8), and a missense allele (rs2231142) was associated with a reduced response (P = 3 × 10−7) in the meta‐analysis. Isotopic uptake studies in cells demonstrated that BCRP transports allopurinol and genetic variants in ABCG2 affect this transport. Collectively, this first GWAS of allopurinol response demonstrates that ABCG2 is a key determinant of response to the drug.
The ongoing trend of increasing air temperatures will potentially affect soil organic matter (SOM) turnover and soil C-CO2 emissions in terrestrial ecosystems of Maritime Antarctica. The effects of ...SOM quality on this process remain little explored. We evaluated (i) the quantity and quality of soil organic matter and (ii) the potential of C release through CO2 emissions in lab conditions in different soil types from Maritime Antarctica. Soil samples (0–10 and 10–20cm) were collected in Keller Peninsula and the vicinity of Arctowski station, to determine the quantity and quality of organic matter and the potential to emit CO2 under different temperature scenarios (2, 5, 8 and 11°C) in lab. Soil organic matter mineralization is low, especially in soils with low organic C and N contents. Recalcitrant C form is predominant, especially in the passive pool, which is correlated with humic substances. Ornithogenic soils had greater C and N contents (reaching to 43.15gkg−1 and 5.22gkg−1 for total organic carbon and nitrogen, respectively). C and N were more present in the humic acid fraction. Lowest C mineralization was recorded from shallow soils on basaltic/andesites. C mineralization rates at 2°C were significant lower than at higher temperatures. Ornithogenic soils presented the lowest values of C-CO2 mineralized by g of C. On the other hand, shallow soils on basaltic/andesites were the most sensitive sites to emit C-CO2 by g of C. With permafrost degradation, soils on basaltic/andesites and sulfates are expected to release more C-CO2 than ornithogenic soils. With greater clay contents, more protection was afforded to soil organic matter, with lower microbial activity and mineralization. The trend of soil temperature increases will favor C-CO2 emissions, especially in the reduced pool of C stored and protected on permafrost, or in occasional Histosols.
Display omitted
•Soil organic matter dynamics and C-CO2 emissions were evaluated.•Ornithogenic soils had greater organic carbon and nitrogen contents.•Shallow soils on basaltic/andesites were the most sensitive sites to emit C-CO2.•The trend of soil temperature increases will favor C-CO2 emissions.
PDF
