57 research outputs found
Radio Galaxy Zoo: Towards building the first multi-purpose foundation model for radio astronomy with self-supervised learning
In this work, we apply self-supervised learning with instance differentiation
to learn a robust, multi-purpose representation for image analysis of resolved
extragalactic continuum images. We train a multi-use model which compresses our
unlabelled data into a structured, low dimensional representation which can be
used for a variety of downstream tasks (e.g. classification, similarity
search). We exceed baseline supervised Fanaroff-Riley classification
performance by a statistically significant margin, with our model reducing the
test set error by up to half. Our model is also able to maintain high
classification accuracy with very few labels, with only 7.79% error when only
using 145 labels. We further demonstrate that by using our foundation model,
users can efficiently trade off compute, human labelling cost and test set
accuracy according to their respective budgets, allowing for efficient
classification in a wide variety of scenarios. We highlight the
generalizability of our model by showing that it enables accurate
classification in a label scarce regime with data from the new MIGHTEE survey
without any hyper-parameter tuning, where it improves upon the baseline by ~8%.
Visualizations of our labelled and un-labelled data show that our model's
representation space is structured with respect to physical properties of the
sources, such as angular source extent. We show that the learned representation
is scientifically useful even if no labels are available by performing a
similarity search, finding hybrid sources in the RGZ DR1 data-set without any
labels. We show that good augmentation design and hyper-parameter choice can
help achieve peak performance, while emphasising that optimal hyper-parameters
are not required to obtain benefits from self-supervised pre-training
Mutations in succinate dehydrogenase B (SDHB) enhance neutrophil survival independent of HIF-1α expression.
status: publishe
Functional Redundancy of Class I Phosphoinositide 3-Kinase (PI3K) Isoforms in Signaling Growth Factor-Mediated Human Neutrophil Survival
We have investigated the contribution of individual phosphoinositide 3-kinase (PI3K) Class I isoforms to the regulation of neutrophil survival using (i) a panel of commercially available small molecule isoform-selective PI3K Class I inhibitors, (ii) novel inhibitors, which target single or multiple Class I isoforms (PI3Kα, PI3Kβ, PI3Kδ, and PI3Kγ), and (iii) transgenic mice lacking functional PI3K isoforms (p110δKOγKO or p110γKO). Our data suggest that there is considerable functional redundancy amongst Class I PI3Ks (both Class IA and Class IB) with regard to GM-CSF-mediated suppression of neutrophil apoptosis. Hence pharmacological inhibition of any 3 or more PI3K isoforms was required to block the GM-CSF survival response in human neutrophils, with inhibition of individual or any two isoforms having little or no effect. Likewise, isolated blood neutrophils derived from double knockout PI3K p110δKOγKO mice underwent normal time-dependent constitutive apoptosis and displayed identical GM-CSF mediated survival to wild type cells, but were sensitized to pharmacological inhibition of the remaining PI3K isoforms. Surprisingly, the pro-survival neutrophil phenotype observed in patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD) was resilient to inactivation of the PI3K pathway
Galaxy And Mass Assembly: galaxy morphology in the green valley, prominent rings, and looser spiral arms
Galaxies broadly fall into two categories: star-forming (blue) galaxies and quiescent (red) galaxies. In between, one finds the less populated “green valley . Some of these galaxies are suspected to be in the process of ceasing their star-formation through a gradual exhaustion of gas supply or already dead and are experiencing a rejuvenation of star-formation through fuel injection. We use the Galaxy And Mass Assembly database and the Galaxy Zoo citizen science morphological estimates to compare the morphology of galaxies in the green valley against those in the red sequence and blue cloud. Our goal is to examine the structural differences within galaxies that fall in the green valley, and what brings them there. Previous results found disc features such as rings and lenses are more prominently represented in the green valley population. We revisit this with a similar sized data set of galaxies with morphology labels provided by the Galaxy Zoo for the GAMA fields based on new KiDS images. Our aim is to compare qualitatively the results from expert classification to that of citizen science. We observe that ring structures are indeed found more commonly in green valley galaxies compared to their red and blue counterparts. We suggest that ring structures are a consequence of disc galaxies in the green valley actively exhibiting characteristics of fading discs and evolving disc morphology of galaxies. We note that the progression from blue to red correlates with loosening spiral arm structure
IL4Rα signaling abrogates hypoxic neutrophil survival and limits acute lung injury responses <i>in vivo</i>
Rationale: Acute respiratory distress syndrome is defined by the presence of systemic hypoxia and consequent on disordered neutrophilic inflammation. Local mechanisms limiting the duration and magnitude of this neutrophilic response remain poorly understood. Objectives: To test the hypothesis that during acute lung inflammation tissue production of proresolution type 2 cytokines (IL-4 and IL-13) dampens the proinflammatory effects of hypoxia through suppression of HIF-1a (hypoxia-inducible factor-1a)mediated neutrophil adaptation, resulting in resolution of lung injury. Methods: Neutrophil activation of IL4Ra (IL-4 receptor a) signaling pathways was explored ex vivo in human acute respiratory distress syndrome patient samples, in vitro after the culture of human peripheral blood neutrophils with recombinant IL-4 under conditions of hypoxia, and in vivo through the study of IL4Ra-deficient neutrophils in competitive chimera models and wild-type mice treated with IL-4. Measurements and Main Results: IL-4 was elevated in human BAL from patients with acute respiratory distress syndrome, and its receptor was identified on patient blood neutrophils. Treatment of human neutrophils with IL-4 suppressed HIF-1a-dependent hypoxic survival and limited proinflammatory transcriptional responses. Increased neutrophil apoptosis in hypoxia, also observed with IL-13, required active STAT signaling, and was dependent on expression of the oxygen-sensing prolyl hydroxylase PHD2. In vivo, IL-4Ra-deficient neutrophils had a survival advantage within a hypoxic inflamed niche; in contrast, inflamed lung treatment with IL-4 accelerated resolution through increased neutrophil apoptosis. Conclusions: We describe an important interaction whereby IL4Ra-dependent type 2 cytokine signaling can directly inhibit hypoxic neutrophil survival in tissues and promote resolution of neutrophil-mediated acute lung injury
Hypoxia drives murine neutrophil protein scavenging to maintain central carbon metabolism
Limiting dysfunctional neutrophilic inflammation while preserving effective immunity requires a better understanding of the processes that dictate neutrophil function in the tissues. Quantitative mass-spectrometry identified how inflammatory murine neutrophils regulated expression of cell surface receptors, signal transduction networks, and metabolic machinery to shape neutrophil phenotypes in response to hypoxia. Through the tracing of labeled amino acids into metabolic enzymes, proinflammatory mediators, and granule proteins, we demonstrated that ongoing protein synthesis shapes the neutrophil proteome. To maintain energy supplies in the tissues, neutrophils consumed extracellular proteins to fuel central carbon metabolism. The physiological stresses of hypoxia and hypoglycemia, characteristic of inflamed tissues, promoted this extracellular protein scavenging with activation of the lysosomal compartment, further driving exploitation of the protein-rich inflammatory milieu. This study provides a comprehensive map of neutrophil proteomes, analysis of which has led to the identification of active catabolic and anabolic pathways that enable neutrophils to sustain synthetic and effector functions in the tissues
A Zebrafish Model to Study and Therapeutically Manipulate Hypoxia Signaling in Tumorigenesis
Differential roles for the oxygen sensing enzymes PHD1 and PHD3 in the regulation of neutrophil metabolism and function
Macrophage miR-210 induction and metabolic reprogramming in response to pathogen interaction boost life-threatening inflammation
Unbalanced immune responses to pathogens can be life-threatening although the underlying regulatory mechanisms remain unknown. Here, we show a hypoxia-inducible factor 1α–dependent microRNA (miR)–210 up-regulation in monocytes and macrophages upon pathogen interaction. MiR-210 knockout in the hematopoietic lineage or in monocytes/macrophages mitigated the symptoms of endotoxemia, bacteremia, sepsis, and parasitosis, limiting the cytokine storm, organ damage/dysfunction, pathogen spreading, and lethality. Similarly, pharmacologic miR-210 inhibition improved the survival of septic mice. Mechanistically, miR-210 induction in activated macrophages supported a switch toward a proinflammatory state by lessening mitochondria respiration in favor of glycolysis, partly achieved by downmodulating the iron-sulfur cluster assembly enzyme ISCU. In humans, augmented miR-210 levels in circulating monocytes correlated with the incidence of sepsis, while serum levels of monocyte/macrophage-derived miR-210 were associated with sepsis mortality. Together, our data identify miR-210 as a fine-tuning regulator of macrophage metabolism and inflammatory responses, suggesting miR-210–based therapeutic and diagnostic strategies
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