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"Thornton, C."
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Production of ice-nucleating particles (INPs) by fast-growing phytoplankton
Sea spray aerosol contains ice-nucleating particles (INPs), which affect the formation and properties of clouds. Here, we show that aerosols emitted from fast-growing marine phytoplankton produce effective immersion INPs, which nucleate at temperatures significantly warmer than the atmospheric homogeneous freezing (−38.0 ∘C) of pure water. Aerosol sampled over phytoplankton cultures grown in a Marine Aerosol Reference Tank (MART) induced nucleation and freezing at temperatures as high as −15.0 ∘C during exponential phytoplankton growth. This was observed in monospecific cultures representative of two major groups of phytoplankton, namely a cyanobacterium (Synechococcus elongatus) and a diatom (Thalassiosira weissflogii). Ice nucleation occurred at colder temperatures (−28.5 ∘C and below), which were not different from the freezing temperatures of procedural blanks, when the cultures were in the stationary or death phases of growth. Ice nucleation at warmer temperatures was associated with relatively high values of the maximum quantum yield of photosystem II (ΦPSII), an indicator of the physiological status of phytoplankton. High values of ΦPSII indicate the presence of cells with efficient photochemistry and greater potential for photosynthesis. For comparison, field measurements in the North Atlantic Ocean showed that high net growth rates of natural phytoplankton assemblages were associated with marine aerosol that acted as effective immersion INPs at relatively warm temperatures. Data were collected over 4 d at a sampling station maintained in the same water mass as the water column stabilized after deep mixing by a storm. Phytoplankton biomass and net phytoplankton growth rate (0.56 d−1) were greatest over the 24 h preceding the warmest mean ice nucleation temperature (−25.5 ∘C). Collectively, our laboratory and field observations indicate that phytoplankton physiological status is a useful predictor of effective INPs and more reliable than biomass or taxonomic affiliation. Ocean regions associated with fast phytoplankton growth, such as the North Atlantic during the annual spring bloom, may be significant sources of atmospheric INPs.
Journal Article
Automation and control of laser wakefield accelerators using Bayesian optimization
Laser wakefield accelerators promise to revolutionize many areas of accelerator science. However, one of the greatest challenges to their widespread adoption is the difficulty in control and optimization of the accelerator outputs due to coupling between input parameters and the dynamic evolution of the accelerating structure. Here, we use machine learning techniques to automate a 100 MeV-scale accelerator, which optimized its outputs by simultaneously varying up to six parameters including the spectral and spatial phase of the laser and the plasma density and length. Most notably, the model built by the algorithm enabled optimization of the laser evolution that might otherwise have been missed in single-variable scans. Subtle tuning of the laser pulse shape caused an 80% increase in electron beam charge, despite the pulse length changing by just 1%.
Laser wakefield accelerators are compact sources of ultra-relativistic electrons which are highly sensitive to many control parameters. Here the authors present an automated machine learning based method for the efficient multi-dimensional optimization of these plasma-based particle accelerators.
Journal Article
On the evolution of stress and microstructure during general 3D deviatoric straining of granular media
The paper presents results of periodic cell simulations on a polydisperse system of 27 000 elastic spheres. In order to explore general three-dimensional stress space an initially isotropically compressed system is subjected to radial deviatoric strain paths and the corresponding stress and fabric responses are illustrated. It is shown that two parameters can be identified that characterise the stress and fabric respectively during general three-dimensional straining. Each parameter, when plotted against deviatoric strain, provides a unique evolution curve, irrespective of the loading direction. It is demonstrated that, for general states of stress, the magnitude of the deviatoric stress is entirely due to the strong force chains that constitute the sub-network of contacts transmitting greater than average contact forces. It is also demonstrated that the relationship between the Lode angle for stress and the Lode angle for strain can be characterised by the curvature of a circular arc and, for radial deviatoric straining, this constitutes a flow rule that defines the relationship between the directions of the stress and strain-rate vectors. Furthermore, by plotting the characteristic stress parameter against the curvature of the circular arc flow rule, a simple scaling law is obtained.
Journal Article
Long-term high-dose immunoglobulin successfully treats Long COVID patients with pulmonary, neurologic, and cardiologic symptoms
Long COVID is the overarching name for a wide variety of disorders that may follow the diagnosis of acute SARS-COVID-19 infection and persist for weeks to many months. Nearly every organ system may be affected.
We report nine patients suffering with Long COVID for 101 to 547 days. All exhibited significant perturbations of their immune systems, but only one was known to be immunodeficient prior to the studies directed at evaluating them for possible treatment. Neurological and cardiac symptoms were most common. Based on this data and other evidence suggesting autoimmune reactivity, we planned to treat them for 3 months with long-term high-dose immunoglobulin therapy. If there was evidence of benefit at 3 months, the regimen was continued.
The patients' ages ranged from 34 to 79 years-with five male and four female patients, respectively. All nine patients exhibited significant immune perturbations prior to treatment. One patient declined this treatment, and insurance support was not approved for two others. The other six have been treated, and all have had a significant to remarkable clinical benefit.
Long-term high-dose immunoglobulin therapy is an effective therapeutic option for treating patients with Long COVID.
Journal Article
Strong force networks in granular mixtures
Using the results of 3D discrete element method simulations we study the force transmission through binary mixtures of sand and silt sized spheres under one-dimensional compression. Three types of contact are categorized depending on the size of the two spheres in contact. The contributions of each contact type to the deviator stress are dependent on the proportion of silt sized spheres. We demonstrate that the magnitude of the deviator stress is solely due to the normal and tangential forces at contacts transmitting normal forces greater than a characteristic normal force, which is generally slightly greater than the average normal force. The maximum packing efficiency was obtained with the mixture of 30 % silt sized spheres and this mixture corresponds to a transition point when there are enough silt sized particles to start to separate the sand sized particles from each other and establish contacts between silt sized spheres that contribute to the deviator stress.
Journal Article
R-loops and nicks initiate DNA breakage and genome instability in non-growing Escherichia coli
Double-stranded DNA ends, often from replication, drive genomic instability, yet their origin in non-replicating cells is unknown. Here we show that transcriptional RNA/DNA hybrids (R-loops) generate DNA ends that underlie stress-induced mutation and amplification. Depleting RNA/DNA hybrids with overproduced RNase HI reduces both genomic changes, indicating RNA/DNA hybrids as intermediates in both. An Mfd requirement and inhibition by translation implicate transcriptional R-loops. R-loops promote instability by generating DNA ends, shown by their dispensability when ends are provided by I-
Sce
I endonuclease. Both R-loops and single-stranded endonuclease TraI are required for end formation, visualized as foci of a fluorescent end-binding protein. The data suggest that R-loops prime replication forks that collapse at single-stranded nicks, producing ends that instigate genomic instability. The results illuminate how DNA ends form in non-replicating cells, identify R-loops as the earliest known mutation/amplification intermediate, and suggest that genomic instability during stress could be targeted to transcribed regions, accelerating adaptation.
DNA double-strand breaks commonly occur in all replicating cells. Wimberly and colleagues show that in non-replicating cells, aborted transcription/translation forms RNA/DNA hybrid R-loops that prime origin-independent replication, leading to DNA breakage, point mutations and chromosomal rearrangements.
Journal Article
Relation of BMI to fat and fat-free mass among children and adolescents
OBJECTIVE:
Although the body mass index (BMI, kg/m
2
) is widely used as a surrogate measure of adiposity, it is a measure of excess weight, rather than excess body fat, relative to height. We examined the relation of BMI to levels of fat mass and fat-free mass among healthy 5- to 18-y-olds.
METHODS AND PROCEDURES:
Dual-energy X-ray absorptiometry was used to measure fat and fat-free mass among 1196 subjects. These measures were standardized for height by calculating the fat mass index (FMI, fat mass/ht
2
) and the fat-free mass index (FFMI, fat-free mass/ht
2
).
RESULTS:
The variability in FFMI was about 50% of that in FMI, and the accuracy of BMI as a measure of adiposity varied greatly according to the degree of fatness. Among children with a BMI-for-age
≥
85th P, BMI levels were strongly associated with FMI (
r
=0.85–0.96 across sex–age categories). In contrast, among children with a BMI-for-age <50th P, levels of BMI were more strongly associated with FFMI (
r
=0.56–0.83) than with FMI (
r
=0.22–0.65). The relation of BMI to fat mass was markedly nonlinear, and substantial differences in fat mass were seen only at BMI levels ≥85th P.
DISCUSSION:
BMI levels among children should be interpreted with caution. Although a high BMI-for-age is a good indicator of excess fat mass, BMI differences among thinner children can be largely due to fat-free mass.
Journal Article
Artemisia of Halicarnassus: Herodotus' Excellent Counsel
Numerous ancient sources attest that Artemisia of Halicarnassus, a fifth-century bce tyrant whose polis came under Persian rule in 524 bce, figures prominently in Xerxes' naval campaign against Greece. At least since Pompeius Trogus' first-century bce Philippic History, interpretations of Artemisia have juxtaposed her \"virile courage\" (uirilem audaciam) with Xerxes' \"womanish fear\" (muliebrem timorem) primarily as a means of belittling the effeminate non-Greeks. My paper argues that although Herodotus is aware of such interpretations of Artemisia, he depicts her primarily as an excellent counsel, a woman who is not only brave in battle, but who is a wonder primarily because of her intellectual excellences in deliberative rhetoric and \"geo-political\" strategy in the Greco-Persian world.
Journal Article
Signal transducer and activator of transcription-3 licenses Toll-like receptor 4-dependent interleukin (IL)-6 and IL-8 production via IL-6 receptor-positive feedback in endometrial cells
Interleukin 6 (IL-6), acting via the IL-6 receptor (IL6R) and signal transducer and activator of transcription-3 (STAT3), limits neutrophil recruitment once bacterial infections are resolved. Bovine endometritis is an exemplar mucosal disease, characterized by sustained neutrophil infiltration and elevated IL-6 and IL-8, a neutrophil chemoattractant, following postpartum Gram-negative bacterial infection. The present study examined the impact of the IL6R/STAT3 signaling pathway on IL-8 production by primary endometrial cells in response to short- or long-term exposure to lipopolysaccharide (LPS) from Gram-negative bacteria. Tyrosine phosphorylation of STAT3 is required for DNA binding and expression of specific targets genes. Immunoblotting indicated constitutive tyrosine phosphorylation of STAT3 in endometrial cells was impeded by acute exposure to LPS. After 24 h exposure to LPS, STAT3 returned to a tyrosine phosphorylated state, indicating cross-talk between the Toll-like receptor 4 (TLR4) and the IL6R/STAT3 signaling pathways. This was confirmed by short interfering RNA targeting the IL6R, which abrogated the accumulation of IL-6 and IL-8, induced by LPS. Furthermore, there was a differential endometrial cell response, as the accumulation of IL-6 and IL-8 was dependent on STAT3, suppressor of cytokine signaling 3, and Src kinase signaling in stromal cells, but not epithelial cells. In conclusion, positive feedback through the IL6R amplifies LPS-induced IL-6 and IL-8 production in the endometrium. These findings provide a mechanistic insight into how elevated IL-6 concentrations in the postpartum endometrium during bacterial infection leads to marked and sustained neutrophil infiltration.
Journal Article