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We describe the design of the Sunrise Filter Imager (SuFI) and the Image Stabilization and Light Distribution (ISLiD) unit onboard the Sunrise balloon borne solar observatory. This contribution provides the necessary information which is relevant to understand the instruments’ working principles, the relevant technical data, and the necessary information about calibration issues directly related to the science data.

The first science flight of the balloon-borne Sunrise telescope took place in June 2009 from ESRANGE (near Kiruna/Sweden) to Somerset Island in northern Canada. We describe the scientific aims and mission concept of the project and give an overview and a description of the various hardware components: the 1-m main telescope with its postfocus science instruments (the UV filter imager SuFI and the imaging vector magnetograph IMaX) and support instruments (image stabilizing and light distribution system ISLiD and correlating wavefront sensor CWS), the optomechanical support structure and the instrument mounting concept, the gondola structure and the power, pointing, and telemetry systems, and the general electronics architecture. We also explain the optimization of the structural and thermal design of the complete payload. The preparations for the science flight are described, including AIV and ground calibration of the instruments. The course of events during the science flight is outlined, up to the recovery activities. Finally, the in-flight performance of the instrumentation is discussed.

Issue Title: Rosetta: Mission to Comet 67P/Churyumov-Gerasimenko The Rosetta Orbiter Spectrometer for Ion and Neutral Analysis (ROSINA) will answer important questions posed by the mission's main objectives. After Giotto, this will be the first time the volatile part of a comet will be analyzed in situ. This is a very important investigation, as comets, in contrast to meteorites, have maintained most of the volatiles of the solar nebula. To accomplish the very demanding objectives through all the different phases of the comet's activity, ROSINA has unprecedented capabilities including very wide mass range (1 to >300 amu), very high mass resolution (m/Δ m > 3000, i.e. the ability to resolve CO from N^sub 2^ and ^sup 13^C from ^sup 12^CH), very wide dynamic range and high sensitivity, as well as the ability to determine cometary gas velocities, and temperature. ROSINA consists of two mass spectrometers for neutrals and primary ions with complementary capabilities and a pressure sensor. To ensure that absolute gas densities can be determined, each mass spectrometer carries a reservoir of a calibrated gas mixture allowing in-flight calibration. Furthermore, identical flight-spares of all three sensors will serve for detailed analysis of all relevant parameters, in particular the sensitivities for complex organic molecules and their fragmentation patterns in our electron bombardment ion sources.[PUBLICATION ABSTRACT]

Background: Antibodies directed against acetylcholine receptor (AChR) are absent in approximately 15% of patients with gMG. Approved treatment options represent an unmet need in the AChR-antibody (Ab)- gMG population. Efgartigimod is an immunoglobulin G1 (IgG1) antibody Fc fragment that selectively reduces IgG levels by blocking neonatal Fc receptor (FcRn)-mediated IgG recycling. Here, we describe efgartigimod efficacy in AChR-Ab- participants with gMG receiving either efgartigimod IV or subcutaneous (SC) efgartigimod PH20 (coformulated with recombinant human hyaluronidase PH20) across clinical studies. Methods: Post hoc analyses were conducted to examine efficacy and safety of efgartigimod IV and/or efgartigimod PH20 SC in AChR-Ab- participants in ADAPT/ADAPT+ and ADAPT-SC/ADAPT-SC+ trials. Results: Among pooled AChR-Ab- participants (n=56), mean (SE) MG-ADL total score improvement from baseline to Week 3 was -3.7 (Cycle 1: 0.44 [n=55]). Consistent MG-ADL improvements occurred with repeated cycles. Clinically meaningful improvements (CMI; ≥2-point MG-ADL decrease) occurred in 76.4% (n=42/55) of participants (Cycle 1, Week 3). In Cycle 1, 23.2% (n=13/56) of participants achieved minimal symptom expression (MG-ADL 0-1). Similar efficacy results occurred across all cycles. Overall safety profile was similar between AChR-Ab+ and AChR-Ab- participants. Conclusions: Both efgartigimod IV and efgartigimod PH20 SC were well tolerated and led to CMI in participants with AChR-Ab- gMG.

Purpose: The impact of benzodiazepines on the efficacy and safety of esketamine as a rapid-acting antidepressant remains unclear. Materials and Methods: Data from two identically designed, randomized double-blind studies were pooled and analyzed on a post-hoc basis. In both studies, adults with major depressive disorder with acute suicidal ideation or behavior were randomized to placebo or esketamine 84 mg nasal spray twice-weekly for 4 weeks, each with comprehensive standard-ofcare (initial hospitalization and newly initiated or optimized oral antidepressant[s]). Efficacy and safety were analyzed in two groups based on whether patients used concomitant benzodiazepines, which were prohibited within 8 hours before and 4 hours after the first dose of esketamine and within 8 hours of the primary efficacy assessment at 24 hours. The primary efficacy endpoint--change from baseline to 24 hours post-first dose in Montgomery-Asberg Depression Rating Scale (MADRS) total score--was analyzed using ANCOVA. Results: Most patients (309/451, 68.5%) used concomitant benzodiazepines. Greater decrease in MADRS total score was observed with esketamine (mean [SD]: -16.1 [11.73]) versus placebo (-12.6 [10.56]) at 24 hours (least-squares mean difference: -3.7, 95% CI: -5.76, -1.59). The differences between the esketamine and placebo groups were clinically meaningful, irrespective of benzodiazepine use (benzodiazepine: -4.3 [-6.63, -1.89]; no benzodiazepine: -3.1 [-6.62, 0.45]). Among patients taking esketamine, change in MADRS total score was not significantly different between patients taking benzodiazepines (-15.8 [11.27]) versus those not taking benzodiazepines (-16.8 [12.82]) (least-squares mean difference: 1.1, [-2.24, 4.45]). Among esketamine-treated patients, the incidence of sedation was higher with benzodiazepine use, whereas dissociation was similar. Conclusion: Benzodiazepines do not meaningfully affect the rapid-acting antidepressant effect of esketamine at 24 hours post-first dose among patients with MDD and acute suicidal ideation or behavior. Keywords: esketamine, benzodiazepine, depression, suicidal ideation, rapid-acting

Hypoxia inhibits activity and expression of transporters involved in alveolar Na reabsorption and fluid clearance. We studied whether this represents a mechanism for reducing energy consumption or whether it is the consequence of metabolic dysfunction. Oxygen consumption (JO2) of A549 cells and primary rat alveolar type II cells was measured by microrespirometry during normoxia, hypoxia (1.5% O2), and reoxygenation. In both cell types, acute and 24-h hypoxia decreased total JO2 significantly and reoxygenation restored JO2 after 5 min but not after 24 h of hypoxia in A549 cells, whereas recovery was complete in type II cells. In A549 cells under normoxia Na/K-ATPase accounted for ∼ 15% of JO2, whereas Na/K-ATPase–related JO2 was decreased by ∼ 25% in hypoxia. Inhibition of other ion transporters did not affect JO2. Protein synthesis–related JO2 was not affected by acute hypoxia, but decreased by 30% after 24-h hypoxia. Acute and 24-h hypoxia decreased JO2 of A549 cell mitochondrial complexes I, II, and III by 30–40%. Reoxygenation restored complex I activity after acute hypoxia but not after 24-h hypoxia. ATP was decreased 30% after 24-h hypoxia, but lactate production rate was not affected. Reduced nicotinamine adenine dinucleotide was slightly elevated in acute hypoxia. Our findings indicate that inhibition of the Na/K-ATPase by hypoxia contributes little to energy preservation in hypoxia. It remains unclear to what extent hypoxic inhibition of mitochondrial metabolism affects ATP-consuming processes.

We describe the design of the Sunrise Filter Imager (SuFI) and the Image Stabilization and Light Distribution (ISLiD) unit onboard the Sunrise balloon borne solar observatory. This contribution provides the necessary information which is relevant to understand the instruments' working principles, the relevant technical data, and the necessary information about calibration issues directly related to the science data.

The \\(HRI_EUV\\) telescope was calibrated on ground at the Physikalisch-Technische Bundesanstalt (PTB), Germany's national metrology institute, using the Metrology Light Source (MLS) synchrotron in April 2017 during the calibration campaign of the Extreme Ultraviolet Imager (EUI) instrument onboard the Solar Orbiter mission. We use the pre-flight end-to-end calibration and component-level (mirror multilayer coatings, filters, detector) characterization results to establish the beginning-of-life performance of the \\(HRI_EUV\\) telescope which shall serve as a reference for radiometric analysis and monitoring of the telescope in-flight degradation. Calibration activities at component level and end-to-end calibration of the instrument were performed at PTB/MLS synchrotron light source (Berlin, Germany) and the SOLEIL synchrotron. Each component optical property is measured and compared to its semi-empirical model. This pre-flight characterization is used to estimate the parameters of the semi-empirical models. The end-to-end response is measured and validated by comparison with calibration measurements, as well as with its main design performance requirements. The telescope spectral response semi-empirical model is validated by the pre-flight end-to-end ground calibration of the instrument. It is found that \\(HRI_EUV\\) is a highly efficient solar EUV telescope with a peak efficiency superior to 1 e\\(^-\\).ph\\(^-1\\)), low detector noise (\\(\\) 3 e- rms), low dark current at operating temperature, and a pixel saturation above 120 ke- in low-gain or combined image mode. The ground calibration also confirms a well-modeled spectral selectivity and rejection, and low stray light. The EUI instrument achieves state-of-the-art performance in terms of signal-to-noise and image spatial resolution.

Coronal rain is the most dramatic cooling phenomenon of the solar corona and an essential diagnostic tool for the coronal heating properties. A puzzling feature of the solar corona, besides the heating, is its EUV filamentary structure and variability. We aim to identify observable features of the TNE-TI scenario underlying coronal rain at small and large spatial scales, to understand the role it plays in the solar corona. We use EUV datasets at unprecedented spatial resolution of ~240 km from EUI/HRIEUV and SPICE of Solar Orbiter from the spring 2022 perihelion. EUV absorption features produced by coronal rain are detected at scales as small as 260 km. As the rain falls, heating and compression is produced immediately downstream, leading to a small EUV brightening accompanying the fall and producing a \"fireball\" phenomenon. Just prior to impact, a flash-like EUV brightening downstream of the rain, lasting a few minutes is observed for the fastest events. For the first time, we detect the atmospheric response to the rain's impact on the chromosphere and consists of upward propagating rebound shocks and flows partly reheating the loop. The observed widths of the rain clumps are 500 +- 200 km. They exhibit a broad velocity distribution of 10 - 150 km s^-1, peaking below 50 km s^-1. Coronal strands of similar widths are observed along the same loops co-spatial with cool filamentary structure, which we interpret as the CCTR. Matching with the expected cooling, prior to the rain appearance sequential loop brightenings are detected in gradually cooler lines from corona to chromospheric temperatures. Despite the large rain showers, most cannot be detected in AIA 171 in quadrature, indicating that LOS effects play a major role in coronal rain visibility. Still, AIA 304 and SPICE observations reveal that only a small fraction of the rain can be captured by HRIEUV.

Solar irradiance variability has been monitored almost exclusively from the Earth's perspective. We present a method to combine the unprecedented observations of the photospheric magnetic field and continuum intensity from outside the Sun-Earth line, which is being recorded by the Polarimetric and Helioseismic Imager on board the Solar Orbiter mission (SO/PHI), with solar observations recorded from the Earth's perspective to examine the solar irradiance variability from both perspectives simultaneously. Taking SO/PHI magnetograms and continuum intensity images from the cruise phase of the Solar Orbiter mission and concurrent observations from the Helioseismic and Magnetic Imager onboard the Solar Dynamics Observatory (SDO/HMI) as input into the SATIRE-S model, we successfully reconstructed the total solar irradiance variability as apparent from both perspectives. In later stages of the SO mission, the orbital plane will tilt in such a way as to bring the spacecraft away from the ecliptic to heliographic latitudes of up to \\(33^\\). The current study sets the template for the reconstruction of solar irradiance variability as seen from outside the ecliptic from data that SO/PHI is expected to collect from such positions. Such a reconstruction will be beneficial to factoring inclination into how the brightness variations of the Sun compare to those of other cool stars, whose rotation axes are randomly inclined.