Advancing solar magnetic field extrapolations through multi-height magnetic field measurements

Non-linear force-free extrapolations are a common approach to estimate the 3D topology of coronal magnetic fields based on photospheric vector magnetograms. The force-free assumption is a valid approximation at coronal heights, but for the dense plasma conditions in the lower atmosphere, this assumption is not satisfied. In this study, we utilize multi-height magnetic field measurements in combination with physics-informed neural networks to advance solar magnetic field extrapolations. We include a flexible height-mapping, which allows us to account for the different formation heights of the observed magnetic field measurements. The comparison to analytical and simulated magnetic fields demonstrates that including chromospheric magnetic field measurements leads to a significant improvement of our magnetic field extrapolations. We also apply our method to chromospheric line-of-sight magnetograms, from the Vector Spectromagnetograph (VSM) on the Synoptic Optical Long-term Investigations of the Sun (SOLIS) observatory, in combination with photospheric vector magnetograms, from the Helioseismic Magnetic Imager (HMI) onboard the Solar Dynamic Observatory (SDO). The comparison to observations in extreme ultraviolet wavelengths shows that the additional chromospheric information leads to a better agreement with the observed coronal structures. In addition, our method intrinsically provides an estimate of the corrugation of the observed magnetograms. With this new approach, we make efficient use of multi-height magnetic field measurements and advance the realism of coronal magnetic field simulations

Calibrating from Within: Multipoint Internal Calibration of a Quantitative Mass Spectrometric Assay of Serum Methotrexate.

BACKGROUND:Clinical LC-MS/MS assays traditionally require that samples be run in batches with calibration curves in each batch. This approach is inefficient and presents a barrier to random access analysis. We developed an alternative approach called multipoint internal calibration (MPIC) that eliminated the need for batch-mode analysis. METHODS:The new approach used 4 variants of 13C-labeled methotrexate (0.026-10.3 µM) as an internal calibration curve within each sample. One site carried out a comprehensive validation, which included an evaluation of interferences and matrix effects, lower limit of quantification (LLOQ), and 20-day precision. Three sites evaluated assay precision and linearity. MPIC was also compared with traditional LC-MS/MS and an immunoassay. RESULTS:Recovery of spiked analyte was 93%-102%. The LLOQ was validated to be 0.017 µM. Total variability, determined in a 20-day experiment, was 11.5%CV. In a 5-day variability study performed at each site, total imprecision was 3.4 to 16.8%CV. Linearity was validated throughout the calibrator range (r2 > 0.995, slopes = 0.996-1.01). In comparing 40 samples run in each laboratory, the median interlaboratory imprecision was 6.55%CV. MPIC quantification was comparable to both traditional LC-MS/MS and immunoassay (r2 = 0.96-0.98, slopes = 1.04-1.06). Bland-Altman analysis of all comparisons showed biases rarely exceeding 20% when MTX concentrations were >0.4 µM. CONCLUSION:The MPIC method for serum methotrexate quantification was validated in a multisite proof-of-concept study and represents a big step toward random-access LC-MS/MS analysis, which could change the paradigm of mass spectrometry in the clinical laboratory

Multi-point study of the energy release and transport in the 28 March 2022, M4-flare using STIX, EUI, and AIA during the first Solar Orbiter nominal mission perihelion

We present a case study of an M4-class flare on 28 March 2022, near Solar Orbiter's first science perihelion (0.33 AU). Solar Orbiter was 83.5{\deg} west of the Sun-Earth line, making the event appear near the eastern limb, while Earth-orbiting spacecraft observed it near the disk center. The timing and location of the STIX X-ray sources were related to the plasma evolution observed in the EUV by the Extreme Ultraviolet Imager (EUI) on Solar Orbiter and the Atmospheric Imaging Assembly (AIA) on the Solar Dynamics Observatory, and to the chromospheric response observed in 1600 {\AA} by AIA. We performed differential emission measure (DEM) analysis to further characterize the flaring plasma at different subvolumes. The pre-flare magnetic field configuration was analyzed using a nonlinear force-free (NLFF) extrapolation. In addition to the two classical hard X-ray (HXR) footpoints at the ends of the flaring loops, later in the event we observe a nonthermal HXR source at one of the anchor points of the erupting filament. The evolution of the AIA 1600~{\AA} footpoints indicates that this change in footpoint location represents a discontinuity in an otherwise continuous westward motion of the footpoints throughout the flare. The NLFF extrapolation suggests that strongly sheared field lines close to, or possibly even part of, the erupting filament reconnected with a weakly sheared arcade during the first HXR peak. The remainder of these field lines reconnected later in the event, producing the HXR peak at the southern filament footpoint. Our results show that the reconnection between field lines with very different shear in the early phase of the flare plays a crucial role in understanding the motion of the HXR footpoint during later parts of the flare. This generalizes simpler models, such as whipping reconnection, which only consider reconnection propagating along uniformly sheared arcades

SuNeRF: Validation of a 3D Global Reconstruction of the Solar Corona Using Simulated EUV Images

Extreme Ultraviolet (EUV) light emitted by the Sun impacts satellite operations and communications and affects the habitability of planets. Currently, EUV-observing instruments are constrained to viewing the Sun from its equator (i.e., ecliptic), limiting our ability to forecast EUV emission for other viewpoints (e.g. solar poles), and to generalize our knowledge of the Sun-Earth system to other host stars. In this work, we adapt Neural Radiance Fields (NeRFs) to the physical properties of the Sun and demonstrate that non-ecliptic viewpoints could be reconstructed from observations limited to the solar ecliptic. To validate our approach, we train on simulations of solar EUV emission that provide a ground truth for all viewpoints. Our model accurately reconstructs the simulated 3D structure of the Sun, achieving a peak signal-to-noise ratio of 43.3 dB and a mean absolute relative error of 0.3\% for non-ecliptic viewpoints. Our method provides a consistent 3D reconstruction of the Sun from a limited number of viewpoints, thus highlighting the potential to create a virtual instrument for satellite observations of the Sun. Its extension to real observations will provide the missing link to compare the Sun to other stars and to improve space-weather forecasting.Comment: Accepted at Machine Learning and the Physical Sciences workshop, NeurIPS 202

AID/APOBEC-network reconstruction identifies pathways associated with survival in ovarian cancer

Background Building up of pathway-/disease-relevant signatures provides a persuasive tool for understanding the functional relevance of gene alterations and gene network associations in multifactorial human diseases. Ovarian cancer is a highly complex heterogeneous malignancy in respect of tumor anatomy, tumor microenvironment including pro-/antitumor immunity and inflammation; still, it is generally treated as single disease. Thus, further approaches to investigate novel aspects of ovarian cancer pathogenesis aiming to provide a personalized strategy to clinical decision making are of high priority. Herein we assessed the contribution of the AID/APOBEC family and their associated genes given the remarkable ability of AID and APOBECs to edit DNA/RNA, and as such, providing tools for genetic and epigenetic alterations potentially leading to reprogramming of tumor cells, stroma and immune cells. Results We structured the study by three consecutive analytical modules, which include the multigene-based expression profiling in a cohort of patients with primary serous ovarian cancer using a self-created AID/APOBEC-associated gene signature, building up of multivariable survival models with high predictive accuracy and nomination of top-ranked candidate/target genes according to their prognostic impact, and systems biology-based reconstruction of the AID /APOBEC-driven disease-relevant mechanisms using transcriptomics data from ovarian cancer samples. We demonstrated that inclusion of the AID/APOBEC signature-based variables significantly improves the clinicopathological variables-based survival prognostication allowing significant patient stratification. Furthermore, several of the profiling-derived variables such as ID3, PTPRC/CD45, AID, APOBEC3G, and ID2 exceed the prognostic impact of some clinicopathological variables. We next extended the signature-/modeling- based knowledge by extracting top genes co-regulated with target molecules in ovarian cancer tissues and dissected potential networks/pathways/regulators contributing to pathomechanisms. We thereby revealed that the AID/APOBEC- related network in ovarian cancer is particularly associated with remodeling/fibrotic pathways, altered immune response, and autoimmune disorders with inflammatory background. Conclusions The herein study is, to our knowledge, the first one linking expression of entire AID/APOBECs and interacting genes with clinical outcome with respect to survival of cancer patients. Overall, data propose a novel AID/APOBEC-derived survival model for patient risk assessment and reconstitute mapping to molecular pathways. The established study algorithm can be applied further for any biologically relevant signature and any type of diseased tissue

Growth differentiation factor 15 and cardiovascular risk: individual patient meta-analysis

AIMS: Levels of growth differentiation factor 15 (GDF-15), a cytokine secreted in response to cellular stress and inflammation, have been associated with multiple types of cardiovascular (CV) events. However, its comparative prognostic performance across different presentations of atherosclerotic cardiovascular disease (ASCVD) remains unknown. METHODS AND RESULTS: An individual patient meta-analysis was performed using data pooled from eight trials including 53 486 patients. Baseline GDF-15 concentration was analyzed as a continuous variable and using established cutpoints ( 1800 ng/L) to evaluate its prognostic performance for CV death/hospitalization for heart failure (HHF), major adverse cardiovascular events (MACE), and their components using Cox models adjusted for clinical variables and established CV biomarkers. Analyses were further stratified on ASCVD status: acute coronary syndrome (ACS), stabilized after recent ACS, and stable ASCVD. Overall, higher GDF-15 concentration was significantly and independently associated with an increased rate of CV death/HHF and MACE (P < 0.001 for each). However, while GDF-15 showed a robust and consistent independent association with CV death and HHF across all presentations of ASCVD, its prognostic association with future myocardial infarction (MI) and stroke only remained significant in patients stabilized after recent ACS or with stable ASCVD [hazard ratio (HR): 1.24, 95% confidence interval (CI): 1.17-1.31 and HR: 1.16, 95% CI: 1.05-1.28 for MI and stroke, respectively] and not in ACS (HR: 0.98, 95% CI: 0.90-1.06 and HR: 0.87, 95% CI: 0.39-1.92, respectively). CONCLUSION: Growth differentiation factor 15 consistently adds prognostic information for CV death and HHF across the spectrum of ASCVD. GDF-15 also adds prognostic information for MI and stroke beyond clinical risk factors and cardiac biomarkers but not in the setting of ACS

IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper

Currently, testing for immunoglobulin E (IgE) sensitization is the cornerstone of diagnostic evaluation in suspected allergic conditions. This review provides a thorough and updated critical appraisal of the most frequently used diagnostic tests, both in vivo and in vitro. It discusses skin tests, challenges, and serological and cellular in vitro tests, and provides an overview of indications, advantages and disadvantages of each in conditions such as respiratory, food, venom, drug, and occupational allergy. Skin prick testing remains the first line approach in most instances; the added value of serum specific IgE to whole allergen extracts or components, as well as the role of basophil activation tests, is evaluated. Unproven, non-validated, diagnostic tests are also discussed. Throughout the review, the reader must bear in mind the relevance of differentiating between sensitization and allergy; the latter entails not only allergic sensitization, but also clinically relevant symptoms triggered by the culprit allergen