Plasma exosomes from children with juvenile dermatomyositis are taken up by human aortic endothelial cells and are associated with altered gene expression in those cells

BACKGROUND: The pathology of juvenile dermatomyositis (JDM) is characterized by prominent vessel wall and perivascular inflammation. This feature of the disease has remained unexplained and under-investigated. We have hypothesized that plasma exosomes, which play an important role in inter-cellular communication, may play a role in the vascular injury associated with JDM. OBJECTIVE: To characterize the circulating exosomes of children with JDM and determine whether the small RNA cargoes within those exosomes are capable of altering transcriptional programs within endothelial cells. DESIGN/METHODS: We purified exosomes from plasma samples of children with active, untreated JDM (n = 6) and healthy controls (n = 9). We characterized the small RNA cargoes in JDM and control exosomes by RNA sequencing using the Illumina HiSeq 2500 platform. We then incubated isolated exosomes from healthy controls and children with JDM with cultured human aortic endothelial cells (HAEC) for 24 h. Fluorescence microscopy was used to confirm that both control and JDM exosomes were taken up by HAEC. RNA was then purified from HAEC that had been incubated with either control or JDM exosomes and sequenced on the Illumina platform. Differential expression of mRNAs from HAEC incubated with control or JDM exosomes was ascertained using standard computational methods. Finally, we assessed the degree to which differential gene expression in HAEC could be attributed to the different small RNA cargoes in JDM vs control exosomes using conventional and novel analytic methods. RESULTS: We identified 10 small RNA molecules that showed differential abundance when we compared JDM and healthy control exosomes. Fluorescence microscopy of labeled exosomes confirmed that both JDM and control exosomes were taken up by HAEC. Differential gene expression analysis revealed 59 genes that showed differential expression between HAEC incubated with JDM exosomes vs HAEC incubated with exosomes from controls. Statistical analysis of gene expression data demonstrated that multiple miRNAs exerted transcriptional control on multiple genes with HAEC. CONCLUSIONS: Plasma exosomes from children with active, untreated JDM are taken up by HAEC and are associated with alterations in gene expression in those cells. These findings provide new insight into potential mechanisms leading to the targeting of vascular tissue by the immune system in JDM

Andreev Reflections in Micrometer-Scale Normal-Insulator-Superconductor Tunnel Junctions

Understanding the subgap behavior of Normal-Insulator-Superconductor (NIS) tunnel junctions is important in order to be able to accurately model the thermal properties of the junctions. Hekking and Nazarov developed a theory in which NIS subgap current in thin-film structures can be modeled by multiple Andreev reflections. In their theory, the current due to Andreev reflections depends on the junction area and the junction resistance area product. We have measured the current due to Andreev reflections in NIS tunnel junctions for various junction sizes and junction resistance area products and found that the multiple reflection theory is in agreement with our data

The invisible power of fairness. How machine learning shapes democracy

Many machine learning systems make extensive use of large amounts of data regarding human behaviors. Several researchers have found various discriminatory practices related to the use of human-related machine learning systems, for example in the field of criminal justice, credit scoring and advertising. Fair machine learning is therefore emerging as a new field of study to mitigate biases that are inadvertently incorporated into algorithms. Data scientists and computer engineers are making various efforts to provide definitions of fairness. In this paper, we provide an overview of the most widespread definitions of fairness in the field of machine learning, arguing that the ideas highlighting each formalization are closely related to different ideas of justice and to different interpretations of democracy embedded in our culture. This work intends to analyze the definitions of fairness that have been proposed to date to interpret the underlying criteria and to relate them to different ideas of democracy.Comment: 12 pages, 1 figure, preprint version, submitted to The 32nd Canadian Conference on Artificial Intelligence that will take place in Kingston, Ontario, May 28 to May 31, 201

Managing the Unmanageable: A Two-Staged Palliative Resection to Control Life-Threatening Duodenal Bleeding Due to Recurrent Paraganglioma

BACKGROUND This report presents therapeutic decision-making and management of refractory, life-threatening duodenal bleeding in a young man with recurrent metastatic retroperitoneal paraganglioma. CASE REPORT The patient had been symptom free for 8 years after radioactive MIBG (metaiodobenzylguanidine) therapy. Failure of endoscopic or angiographic bleeding control led to urgent need to evaluate possible endocrine functional status, tumor curability, safety of incomplete resection, intra- and postoperative support needs, and anticipated recovery potential and postoperative function. Aside from these considerations, impact of tumor biology, alternative therapeutic options, current management guidelines, and ethical challenges of resource utilization for such complex palliative operative intervention were reviewed. CONCLUSIONS Based on the observed outcomes after an urgent presentation of an unusual tumor-related complication, palliation-intent therapy was justifiable even if significant treatment-related risks were expected and complex resources were required

Crowd disagreement about medical images is informative

Classifiers for medical image analysis are often trained with a single consensus label, based on combining labels given by experts or crowds. However, disagreement between annotators may be informative, and thus removing it may not be the best strategy. As a proof of concept, we predict whether a skin lesion from the ISIC 2017 dataset is a melanoma or not, based on crowd annotations of visual characteristics of that lesion. We compare using the mean annotations, illustrating consensus, to standard deviations and other distribution moments, illustrating disagreement. We show that the mean annotations perform best, but that the disagreement measures are still informative. We also make the crowd annotations used in this paper available at \url{https://figshare.com/s/5cbbce14647b66286544}.Comment: Accepted for publication at MICCAI LABELS 201

Epineuston vortex recapture enhances thrust in tiny water skaters

Vortex recapture underpins the exceptional mobility of nature’s finest fliers and swimmers. Utilized by agile fruit flies and efficient jellyfish, this phenomenon is well-documented in bulk fluids. Despite extensive studies on the neustontextemdasha vital fluidic interface where diverse life forms interact between air and watertextemdashneuston vortical hydrodynamics remain unexplored. We investigate epineuston (on water) vortical hydrodynamics in Microvelia americana, one of the smallest and fastest water striders, skating at 50 BL/s (15 cm/s). Their middle legs shed counter-rotating vortices, re-energized by hind legs, demonstrating epineuston vortex recapture. High-speed imaging, particle imaging velocimetry, physical models, and CFD simulations show re-energization increases thrust by creating positive pressure at the hind tarsi, acting as a virtual wall. This vortex capture is facilitated by the tripod gait, leg morphology, and precise spatio-temporal placement of the hind tarsi during the power stroke. Our study extends vortex recapture principles from bulk fluids to the neuston, offering insights into efficient epineuston locomotion, where surface tension and capillary waves challenge movement. Understanding epineuston vortex hydrodynamics can guide the development of energy-efficient microrobots to explore the planet’s neuston niches, critical frontlines of climate change and pollution.Competing Interest StatementThe authors have declared no competing interest

Complex ecologies of trust in data practices and data-driven systems

Trust in data practices and data-driven systems is widely seen as both important and elusive. A data trust deficit has been identified, to which proposed solutions are often localised or individualised, focusing either on what institutions can do to increase user trust in their data practices or on data management models that empower the individual user. Scholarship on trust often focuses on typologies of trust. This paper shifts the emphasis to those doing the trusting, by presenting findings from empirical research which explored user perspectives on the data practices of the BBC. These findings challenge the assumption that localised or individualised solutions can be effective. They also suggest that conceptualisations of trust in data practices need to account for the complex range of factors which come into play in relation to trust in data and so move beyond the production of typologies. In this paper, we propose the concept of ‘complex ecologies of trust’ as a way of addressing all of these issues

Spitzer Observations of Low Luminosity Isolated and Low Surface Brightness Galaxies

We examine the infrared properties of five low surface brightness galaxies (LSBGs) and compare them with related but higher surface brightness galaxies, using Spitzer Space Telescope images and spectra. All the LSBGs are detected in the 3.6 and 4.5um bands, representing the stellar population. All but one are detected at 5.8 and 8.0um, revealing emission from hot dust and aromatic molecules, though many are faint or point-like at these wavelengths. Detections of LSBGs at the far-infrared wavelengths, 24, 70, and 160um, are varied in morphology and brightness, with only two detections at 160um, resulting in highly varied spectral energy distributions. Consistent with previous expectations for these galaxies, we find that detectable dust components exist for only some LSBGs, with the strength of dust emission dependent on the existence of bright star forming regions. However, the far-infrared emission may be relatively weak compared with normal star-forming galaxies.Comment: 20 pages, 8 figures, accepted to Ap

Asymptotic stability, concentration, and oscillation in harmonic map heat-flow, Landau-Lifshitz, and Schroedinger maps on R^2

We consider the Landau-Lifshitz equations of ferromagnetism (including the harmonic map heat-flow and Schroedinger flow as special cases) for degree m equivariant maps from R^2 to S^2. If m \geq 3, we prove that near-minimal energy solutions converge to a harmonic map as t goes to infinity (asymptotic stability), extending previous work down to degree m = 3. Due to slow spatial decay of the harmonic map components, a new approach is needed for m=3, involving (among other tools) a "normal form" for the parameter dynamics, and the 2D radial double-endpoint Strichartz estimate for Schroedinger operators with sufficiently repulsive potentials (which may be of some independent interest). When m=2 this asymptotic stability may fail: in the case of heat-flow with a further symmetry restriction, we show that more exotic asymptotics are possible, including infinite-time concentration (blow-up), and even "eternal oscillation".Comment: 34 page

Academic freedom in Europe: reviewing UNESCO’s recommendation

This paper examines the compliance of universities in the European Union with the UNESCO Recommendation concerning the Status of Higher–Education Teaching Personnel, which deals primarily with protection for academic freedom. The paper briefly surveys the European genesis of the modern research university and academic freedom, before evaluating compliance with the UNESCO recommendation on institutional autonomy, academic freedom, university governance and tenure. Following from this, the paper examines the reasons for the generally low level of compliance with the UNESCO Recommendation within the EU states, and considers how such compliance could be improved