Pulse control protocols for preserving coherence in dipolar-coupled nuclear spin baths.

Coherence of solid state spin qubits is limited by decoherence and random fluctuations in the spin bath environment. Here we develop spin bath control sequences which simultaneously suppress the fluctuations arising from intrabath interactions and inhomogeneity. Experiments on neutral self-assembled quantum dots yield up to a five-fold increase in coherence of a bare nuclear spin bath. Numerical simulations agree with experiments and reveal emergent thermodynamic behaviour where fluctuations are ultimately caused by irreversible conversion of coherence into many-body quantum entanglement. Simulations show that for homogeneous spin baths our sequences are efficient with non-ideal control pulses, while inhomogeneous bath coherence is inherently limited even under ideal-pulse control, especially for strongly correlated spin-9/2 baths. These results highlight the limitations of self-assembled quantum dots and advantages of strain-free dots, where our sequences can be used to control the fluctuations of a homogeneous nuclear spin bath and potentially improve electron spin qubit coherence

Single-cell RNA-sequencing resolves self-antigen expression during mTEC development

The crucial capability of T cells for discrimination between self and non-self peptides is based on negative selection of developing thymocytes by medullary thymic epithelial cells (mTECs). The mTECs purge autoreactive T cells by expression of cell-type specific genes referred to as tissue-restricted antigens (TRAs). Although the autoimmune regulator (AIRE) protein is known to promote the expression of a subset of TRAs, its mechanism of action is still not fully understood. The expression of TRAs that are not under the control of AIRE also needs further characterization. Furthermore, expression patterns of TRA genes have been suggested to change over the course of mTEC development. Herein we have used single-cell RNA-sequencing to resolve patterns of TRA expression during mTEC development. Our data indicated that mTEC development consists of three distinct stages, correlating with previously described jTEC, mTEChi and mTEClo phenotypes. For each subpopulation, we have identified marker genes useful in future studies. Aire-induced TRAs were switched on during jTEC-mTEC transition and were expressed in genomic clusters, while otherwise the subsets expressed largely overlapping sets of TRAs. Moreover, population-level analysis of TRA expression frequencies suggested that such differences might not be necessary to achieve efficient thymocyte selection.RM is supported by a PhD Fellowship from the Fundação para a Ciência e Tecnologia, Portugal (SFRH/ BD/51950/2012). XZ is supported by an Advanced Postdoc Mobility Fellowship from the Swiss National Science Foundation (SNSF, grant number P300P2_151352). Part of the work was performed during XZ’s visit to the Simons Institute for the Theory of Computing. TL is supported by the Academy of Finland (Decision 311081). The authors would like to thank Bee Ling Ng and the staff of the Cytometry Core Facility, and Stephan Lorenz and the staff of the Single Cell Genomics Core Facility for their contribution. Mark Lynch is acknowledged for technical assistance with the Fluidigm C1 platform. Mike Stubbington and Kylie James are acknowledged for revising the language of the manuscript. We thank Sarah Teichmann for help and discussions regarding the manuscript.info:eu-repo/semantics/publishedVersio

Peer Support Workers in Health:A Qualitative Metasynthesis of Their Experiences

Peer support models, where an individual has a specific illness or lifestyle experience and supports others experiencing similar challenges, have frequently been used in different fields of healthcare to successfully engage hard-to-reach groups. Despite recognition of their value, the impact of these roles on the peer has not been systematically assessed. By synthesising the qualitative literature we sought to review such an impact, providing a foundation for designing future clinical peer models.Systematic review and qualitative metasynthesis of studies found in Medline, CINAHL or Scopus documenting peer worker experiences.1,528 papers were found, with 34 meeting the criteria of this study. Findings were synthesised to reveal core constructs of reframing identity through reciprocal relations and the therapeutic use of self, enhancing responsibility.The ability of the Peer Support Worker to actively engage with other marginalised or excluded individuals based on their unique insight into their own experience supports a therapeutic model of care based on appropriately sharing their story. Our findings have key implications for maximising the effectiveness of Peer Support Workers and in contributing their perspective to the development of a therapeutic model of care

<em>Euclid</em>: Early Release Observations – Deep anatomy of nearby galaxies

\ua9 The Authors 2025. Euclid is poised to make significant advances in the study of nearby galaxies in the Local Universe. Here we present a first look at six galaxies observed for the Nearby Galaxy Showcase as part of the Euclid Early Release Observations acquired between August and November, 2023. These targets, three dwarf galaxies (Holmberg II, IC 10, and NGC 6822) and three spirals (IC 342, NGC 2403, and NGC 6744), range in distance from about 0.5 Mpc to 8.8 Mpc. We first assess the surface brightness depths in the stacked Euclid images, and confirm previous estimates in 100 arcsec2 regions for Visible Camera (VIS) of 1σ limits of 30.5 mag arcsec-2, but find deeper than previous estimates for Near-Infrared Spectrometer and Photometer (NISP) with 1σ = 29.2–29.4 mag arcsec-2. By combining Euclid HE, YE, and IE into RGB images, we illustrate the large field of view (FoV) covered by a single reference observing sequence (ROS), together with exquisite detail on scales of &lt;1–4 parsecs in these nearby galaxies. Our analysis of radial surface brightness and color profiles demonstrates that the photometric calibration of Euclid is consistent with what is expected for galaxy colors according to stellar synthesis models. We perform standard source-selection techniques for stellar photometry, and find approximately 1.3 million stars across the six galaxy fields. After subtracting foreground stars and background galaxies, and applying a color and magnitude selection, we extract stellar populations of different ages for the six galaxies. The resolved stellar photometry obtained with Euclid allows us to constrain the star-formation histories of these galaxies, which we do by disentangling the distributions of young stars and asymptotic giant branch and red giant branch stellar populations. We finally examine two galaxies individually for surrounding systems of dwarf galaxy satellites and globular cluster populations. Our analysis of the ensemble of dwarf satellites around NGC 6744 recovers all the previously known dwarf satellites within the Euclid FoV, and also confirms the satellite nature of a previously identified candidate, dw1909m6341, a nucleated dwarf spheroidal at the end of a spiral arm. Our new census of the globular clusters around NGC 2403 yields nine new star-cluster candidates, eight of which exhibit colors indicative of evolved stellar populations. In summary, our first investigation of six “showcase” galaxies demonstrates that Euclid is a powerful probe of stellar structure and stellar populations in nearby galaxies, and will provide vastly improved statistics on dwarf satellite systems and extragalactic globular clusters in the local Universe, among many other exciting results

Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19

The biological determinants underlying the range of coronavirus 2019 (COVID-19) clinical manifestations are not fully understood. Here, over 1,400 plasma proteins and 2,600 single-cell immune features comprising cell phenotype, endogenous signaling activity, and signaling responses to inflammatory ligands are cross-sectionally assessed in peripheral blood from 97 patients with mild, moderate, and severe COVID-19 and 40 uninfected patients. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identify and independently validate a multi-variate model classifying COVID-19 severity (multi-class area under the curve [AUC]training = 0.799, p = 4.2e-6; multi-class AUCvalidation = 0.773, p = 7.7e-6). Examination of informative model features reveals biological signatures of COVID-19 severity, including the dysregulation of JAK/STAT, MAPK/mTOR, and nuclear factor κB (NF-κB) immune signaling networks in addition to recapitulating known hallmarks of COVID-19. These results provide a set of early determinants of COVID-19 severity that may point to therapeutic targets for prevention and/or treatment of COVID-19 progression

Euclid II. The VIS instrument

This paper presents the specification, design, and development of the Visible Camera (VIS) on the European Space Agency's mission. VIS is a large optical-band imager with a field of view of 0.54 deg$^2$ sampled at with an array of 609 Megapixels and a spatial resolution of . It will be used to survey approximately 14 000 deg$^2$ of extragalactic sky to measure the distortion of galaxies in the redshift range $z=0.1$--1.5 resulting from weak gravitational lensing, one of the two principal cosmology probes leveraged by With photometric redshifts, the distribution of dark matter can be mapped in three dimensions, and the extent to which this has changed with look-back time can be used to constrain the nature of dark energy and theories of gravity. The entire VIS focal plane will be transmitted to provide the largest images of the Universe from space to date, specified to reach AB with a signal-to-noise ratio S/N in a single broad E (r+i+z)$band over a six-year survey. The particularly challenging aspects of the instrument are the control and calibration of observational biases, which lead to stringent performance requirements and calibration regimes. With its combination of spatial resolution, calibration knowledge, depth, and area covering most of the extra-Galactic sky, VIS will also provide a legacy data set for many other fields. This paper discusses the rationale behind the conception of VIS and describes the instrument design and development, before reporting the prelaunch performance derived from ground calibrations and brief results from the in-orbit commissioning. VIS should reach fainter than AB =25$ with $S/N 10$ for galaxies with a full width at half maximum of in a diameter aperture over the Wide Survey, and $m_ AB for a Deep Survey that will cover more than 50 deg$^2$. The paper also describes how the instrument works with the telescope and survey, and with the science data processing, to extract the cosmological information

Dimethyl fumarate blocks pro-inflammatory cytokine production via inhibition of TLR induced M1 and K63 ubiquitin chain formation

Dimethyl fumarate (DMF) possesses anti-inflammatory properties and is approved for the treatment of psoriasis and multiple sclerosis. While clinically effective, its molecular target has remained elusive - although it is known to activate anti-oxidant pathways. We find that DMF inhibits pro-inflammatory cytokine production in response to TLR agonists independently of the Nrf2-Keap1 anti-oxidant pathway. Instead we show that DMF can inhibit the E2 conjugating enzymes involved in K63 and M1 polyubiquitin chain formation both in vitro and in cells. The formation of K63 and M1 chains is required to link TLR activation to downstream signaling, and consistent with the block in K63 and/or M1 chain formation, DMF inhibits NFκB and ERK1/2 activation, resulting in a loss of pro-inflammatory cytokine production. Together these results reveal a new molecular target for DMF and show that a clinically approved drug inhibits M1 and K63 chain formation in TLR induced signaling complexes. Selective targeting of E2s may therefore be a viable strategy for autoimmunity

Measuring 129Xe transfer across the blood‐brain barrier using MR spectroscopy

Purpose This study develops a tracer kinetic model of xenon uptake in the human brain to determine the transfer rate of inhaled hyperpolarized 129Xe from cerebral blood to gray matter that accounts for the effects of cerebral physiology, perfusion and magnetization dynamics. The 129Xe transfer rate is expressed using a tracer transfer coefficient, which estimates the quantity of hyperpolarized 129Xe dissolved in cerebral blood under exchange with depolarized 129Xe dissolved in gray matter under equilibrium of concentration. Theory and Methods Time‐resolved MR spectra of hyperpolarized 129Xe dissolved in the human brain were acquired from three healthy volunteers. Acquired spectra were numerically fitted with five Lorentzian peaks in accordance with known 129Xe brain spectral peaks. The signal dynamics of spectral peaks for gray matter and red blood cells were quantified, and correction for the 129Xe T1 dependence upon blood oxygenation was applied. 129Xe transfer dynamics determined from the ratio of the peaks for gray matter and red blood cells was numerically fitted with the developed tracer kinetic model. Results For all the acquired NMR spectra, the developed tracer kinetic model fitted the data with tracer transfer coefficients between 0.1 and 0.14. Conclusion In this study, a tracer kinetic model was developed and validated that estimates the transfer rate of HP 129Xe from cerebral blood to gray matter in the human brain