Hinode/Extreme-Ultraviolet Imaging Spectrometer Observations of the Temperature Structure of the Quiet Corona

We present a Differential Emission Measure (DEM) analysis of the quiet solar corona on disk using data obtained by the Extreme-ultraviolet Imaging Spectrometer (EIS) on {\it Hinode}. We show that the expected quiet Sun DEM distribution can be recovered from judiciously selected lines, and that their average intensities can be reproduced to within 30%. We present a subset of these selected lines spanning the temperature range $\log$ T = 5.6 to 6.4 K that can be used to derive the DEM distribution reliably. The subset can be used without the need for extensive measurements and the observed intensities can be reproduced to within the estimated uncertainty in the pre-launch calibration of EIS. Furthermore, using this subset, we also demonstrate that the quiet coronal DEM distribution can be recovered on size scales down to the spatial resolution of the instrument (1$"$ pixels). The subset will therefore be useful for studies of small-scale spatial inhomogeneities in the coronal temperature structure, for example, in addition to studies requiring multiple DEM derivations in space or time. We apply the subset to 45 quiet Sun datasets taken in the period 2007 January to April, and show that although the absolute magnitude of the coronal DEM may scale with the amount of released energy, the shape of the distribution is very similar up to at least $\log$ T $\sim$ 6.2 K in all cases. This result is consistent with the view that the {\it shape} of the quiet Sun DEM is mainly a function of the radiating and conducting properties of the plasma and is fairly insensitive to the location and rate of energy deposition. This {\it universal} DEM may be sensitive to other factors such as loop geometry, flows, and the heating mechanism, but if so they cannot vary significantly from quiet Sun region to region.Comment: Version accepted by ApJ and published in ApJ 705. Abridged abstrac

Evidence for Steady Heating: Observations of an Active Region Core with Hinode and TRACE

Previous observations have not been able to exclude the possibility that high temperature active region loops are actually composed of many small scale threads that are in various stages of heating and cooling and only appear to be in equilibrium. With new observations from the EUV Imaging Spectrometer (EIS) and X-ray Telescope (XRT) on \textit{Hinode} we have the ability to investigate the properties of high temperature coronal plasma in extraordinary detail. We examine the emission in the core of an active region and find three independent lines of evidence for steady heating. We find that the emission observed in XRT is generally steady for hours, with a fluctuation level of approximately 15% in an individual pixel. Short-lived impulsive heating events are observed, but they appear to be unrelated to the steady emission that dominates the active region. Furthermore, we find no evidence for warm emission that is spatially correlated with the hot emission, as would be expected if the high temperature loops are the result of impulsive heating. Finally, we also find that intensities in the "moss", the footpoints of high temperature loops, are consistent with steady heating models provided that we account for the local expansion of the loop from the base of the transition region to the corona. In combination, these results provide strong evidence that the heating in the core of an active region is effectively steady, that is, the time between heating events is short relative to the relevant radiative and conductive cooling times.Comment: Minor changes based on the final report from the referee; Movies are available from the first autho

Constraints on the Heating of High Temperature Active Region Loops: Observations from Hinode and SDO

We present observations of high temperature emission in the core of a solar active region using instruments on Hinode and SDO. These multi-instrument observations allow us to determine the distribution of plasma temperatures and follow the evolution of emission at different temperatures. We find that at the apex of the high temperature loops the emission measure distribution is strongly peaked near 4 MK and falls off sharply at both higher and lower temperatures. Perhaps most significantly, the emission measure at 0.5 MK is reduced by more than two orders of magnitude from the peak at 4 MK. We also find that the temporal evolution in broad-band soft X-ray images is relatively constant over about 6 hours of observing. Observations in the cooler SDO/AIA bandpasses generally do not show cooling loops in the core of the active region, consistent with the steady emission observed at high temperatures. These observations suggest that the high temperature loops observed in the core of an active region are close to equilibrium. We find that it is possible to reproduce the relative intensities of high temperature emission lines with a simple, high-frequency heating scenario where heating events occur on time scales much less than a cooling time. In contrast, low-frequency heating scenarios, which are commonly invoked to describe nanoflare models of coronal heating, do not reproduce the relative intensities of high temperature emission lines and predict low-temperature emission that is approximately an order of magnitude too large. We also present an initial look at images from the SDO/AIA 94 A channel, which is sensitive to Fe XVIII.Comment: Movies are available at http://tcrb.nrl.navy.mil/~hwarren/temp/papers/active_region_core/ Paper has been refereed and revise

Modeling Evolving Coronal Loops with Observations from STEREO, Hinode, and TRACE

The high densities, long lifetimes, and narrow emission measure distributions observed in coronal loops with apex temperatures near 1 MK are difficult to reconcile with physical models of the solar atmosphere. It has been proposed that the observed loops are actually composed of sub-resolution ``threads'' that have been heated impulsively and are cooling. We apply this heating scenario to nearly simultaneous observations of an evolving post-flare loop arcade observed with the EUVI/\textit{STEREO}, XRT/\textit{Hinode}, and \textit{TRACE} imagers and the EIS spectrometer on \textit{HINODE}. We find that it is possible to reproduce the extended loop lifetime, high electron density, and the narrow differential emission measure with a multi-thread hydrodynamic model provided that the time scale for the energy release is sufficiently short. The model, however, does not reproduce the evolution of the very high temperature emission observed with XRT. In XRT the emission appears diffuse and it may be that this discrepancy is simply due to the difficulty of isolating individual loops at these temperatures. This discrepancy may also reflect fundamental problems with our understanding of post-reconnection dynamics during the conductive cooling phase of loop evolution.Comment: Revised version submitted to ApJ in response to referee's comment

Characteristics and Evolution of the Magnetic field and Chromospheric Emission in an Active Region Core Observed by Hinode

We describe the characteristics and evolution of the magnetic field and chromospheric emission in an active region core observed by the Solar Optical Telescope on Hinode. Consistent with previous studies, we find that the moss is unipolar, the spatial distribution of magnetic flux evolves slowly, and the magnetic field is only moderately inclined. We show that the field line inclination and horizontal component are coherent, and that the magnetic field is mostly sheared in the inter-moss regions where the highest magnetic flux variability is seen. Using extrapolations from SP magnetograms we show that the magnetic connectivity in the moss is different than in the quiet Sun because most of the magnetic field extends to significant coronal heights. The magnetic flux, field vector, and chromospheric emission in the moss also appear highly dynamic, but actually show only small scale variations in magnitude on time-scales longer than the cooling times for hydrodynamic loops computed from our extrapolations, suggesting high-frequency (continuous) heating events. Some evidence is found for flux (Ca 2 intensity) changes on the order of 100--200 G (DN) on time-scales of 20--30 mins that could be taken as indicative of low-frequency heating. We find, however, that only a small fraction (10%) of our simulated loops would be expected to cool on these time-scales, and we find no clear evidence that the flux changes consistently produce intensity changes in the chromosphere. The magnetic flux and chromospheric intensity in most individual SOT pixels in the moss vary by less than ~ 20% and ~ 10%, respectively, on loop cooling time-scales. In view of the high energy requirements of the chromosphere, we suggest that these variations could be sufficient for the heating of `warm' EUV loops, but that the high basal levels may be more important for powering the hot core loops rooted in the moss.Comment: Accepted by ApJ, 16 pages, 20 figures. Abridged abstract (original is in PDF file). Figures 1 & 2 are reduced resolution to meet size limit

Identification of rare DNA variants in mitochondrial disorders with improved array-based sequencing.

A common goal in the discovery of rare functional DNA variants via medical resequencing is to incur a relatively lower proportion of false positive base-calls. We developed a novel statistical method for resequencing arrays (SRMA, sequence robust multi-array analysis) to increase the accuracy of detecting rare variants and reduce the costs in subsequent sequence verifications required in medical applications. SRMA includes single and multi-array analysis and accounts for technical variables as well as the possibility of both low- and high-frequency genomic variation. The confidence of each base-call was ranked using two quality measures. In comparison to Sanger capillary sequencing, we achieved a false discovery rate of 2% (false positive rate 1.2 × 10⁻⁵, false negative rate 5%), which is similar to automated second-generation sequencing technologies. Applied to the analysis of 39 nuclear candidate genes in disorders of mitochondrial DNA (mtDNA) maintenance, we confirmed mutations in the DNA polymerase gamma POLG in positive control cases, and identified novel rare variants in previously undiagnosed cases in the mitochondrial topoisomerase TOP1MT, the mismatch repair enzyme MUTYH, and the apurinic-apyrimidinic endonuclease APEX2. Some patients carried rare heterozygous variants in several functionally interacting genes, which could indicate synergistic genetic effects in these clinically similar disorders

DNA storage in thermoresponsive microcapsules for repeated random multiplexed data access

In support of the publication "DNA storage in thermoresponsive microcapsules for repeated random multiplexed data access" we share the following datasets and code: AutoCAD drawing of the microfluidic trapping device. Sequences of the DNA used to encode the 25 files used in the current study. FASTQ-files of the sequencing experiments of Figures 5b and d. Python scripts that allow for the reproduction of our sequencing data analysis. The code has been tested on MacOS 13.0.1, Python 3.7.13, samtools 1.16.1 and BWA 0.7.17

Engineering cytokine therapeutics

Cytokines have pivotal roles in immunity, making them attractive as therapeutics for a variety of immune-related disorders. However, the widespread clinical use of cytokines has been limited by their short blood half-lives and severe side effects caused by low specificity and unfavourable biodistribution. Innovations in bioengineering have aided in advancing our knowledge of cytokine biology and yielded new technologies for cytokine engineering. In this Review, we discuss how the development of bioanalytical methods, such as sequencing and high-resolution imaging combined with genetic techniques, have facilitated a better understanding of cytokine biology. We then present an overview of therapeutics arising from cytokine re-engineering, targeting and delivery, mRNA therapeutics and cell therapy. We also highlight the application of these strategies to adjust the immunological imbalance in different immune-mediated disorders, including cancer, infection and autoimmune diseases. Finally, we look ahead to the hurdles that must be overcome before cytokine therapeutics can live up to their full potential

Fault tolerant architectures for superconducting qubits

In this short review, I draw attention to new developments in the theory of fault tolerance in quantum computation that may give concrete direction to future work in the development of superconducting qubit systems. The basics of quantum error correction codes, which I will briefly review, have not significantly changed since their introduction fifteen years ago. But an interesting picture has emerged of an efficient use of these codes that may put fault tolerant operation within reach. It is now understood that two dimensional surface codes, close relatives of the original toric code of Kitaev, can be adapted to effectively perform logical gate operations in a very simple planar architecture, with error thresholds for fault tolerant operation simulated to be 0.75%. This architecture uses topological ideas in its functioning, but it is not 'topological quantum computation' -- there are no non-abelian anyons in sight. I offer some speculations on the crucial pieces of superconducting hardware that could be demonstrated in the next couple of years that would be clear stepping stones towards this surface-code architecture.Comment: 28 pages, 10 figures. For the Nobel Symposium on Qubits for Quantum Information, submitted to Physica Scripta. v. 2 Corrections and small changes to reference

Resolving sepsis-induced immunoparalysis via trained immunity by targeting interleukin-4 to myeloid cells.

Immunoparalysis is a compensatory and persistent anti-inflammatory response to trauma, sepsis or another serious insult, which increases the risk of opportunistic infections, morbidity and mortality. Here, we show that in cultured primary human monocytes, interleukin-4 (IL4) inhibits acute inflammation, while simultaneously inducing a long-lasting innate immune memory named trained immunity. To take advantage of this paradoxical IL4 feature in vivo, we developed a fusion protein of apolipoprotein A1 (apoA1) and IL4, which integrates into a lipid nanoparticle. In mice and non-human primates, an intravenously injected apoA1-IL4-embedding nanoparticle targets myeloid-cell-rich haematopoietic organs, in particular, the spleen and bone marrow. We subsequently demonstrate that IL4 nanotherapy resolved immunoparalysis in mice with lipopolysaccharide-induced hyperinflammation, as well as in ex vivo human sepsis models and in experimental endotoxemia. Our findings support the translational development of nanoparticle formulations of apoA1-IL4 for the treatment of patients with sepsis at risk of immunoparalysis-induced complications.We thank M. Jaeger (Radboudumc) for kindly providing flourescein isothiocyanate-labelled Candida albicans. D. Williams (East Tennessee State University) provided the β-glucan we used in our initial experiments. H. Lemmers (Radboudumc) kindly prepared the purified lipopolysaccharide used for stimulation of primary human monocytes and macrophages. Part of the figures were prepared using (among other software) Biorender.com. B.N. is supported by a National Health and Medical Research Council (Australia) Investigator Grant (APP1173314). This work was supported by National Institutes of Health grants R01 HL144072, R01 CA220234 and P01 HL131478, as well as a Vici grant from the Dutch Research Council NWO and an ERC Advanced Grant (all to W.J.M.M.). M.G.N. was supported by a Spinoza grant from Dutch Research Council NWO and an ERC Advanced Grant (#833247).S