High-Energy Proton Testing of Sensitive Electronics for use on Modular Infrared Molecules and Ices Sensor (MIRMIS) Instrument

The Comet Interceptor (CI) mission is ESA\u27s first F class mission, selected in June 2019. This mission consists of three spacecraft: Spacecraft A (main spacecraft), Spacecraft B1 (supplied by the Japanese space agency JAXA), and Spacecraft B2. In this paper, we highlight the Modular Infrared Molecular and Ices Sensor (MIRMIS) instrument, which is integrated into the CI Spacecraft A\u27s scientific payload. In addition to hardware contributions from Finland (VTT Finland) and the UK (University of Oxford), the MIRMIS instrument team includes members from the University of Helsinki and NASA\u27s Goddard Space Flight Centre. MIRMIS covers the spectral range of 0.9 to ~25 μm. This paper presents the preliminary high-proton-energy radiation test results of MIRMIS’ near-infrared detector arraysensitive electronic components. Proton beam testing is performed to estimate Single Event Effects (SEE) on the PCB boards and SEE and Total Non-Ionizing Dose (TNID)/ Displacement Damage (DD) on the detectors. The tests were conducted at the Paul Scherrer Institute (PSI) Proton Irradiation Facility (PIF), Villigen, Switzerland. The levels for the tests were based on the mission requirements for the ESA Comet Interceptor mission: 3 years (at 1 AU- Segment 1) and 2 years (at 0.9 AU- Segment 2). The DD levels from the analysis were equivalent to 1e11 protons/cm2 with an energy of 50 MeV. The electronics are exposed to high-energy protons causing Single Event Effects (SEE) which may induce potentially destructive and non-destructive effects. The test items primarily included the InGaAs image sensors (SCD Cardinal640, standard and low noise), Xilinx Spartan-6 FPGAs (Field Programmable Gate Arrays), and other proximity electronics. The proton energies were varied from 50 to 200 MeV, at fluxes of 106 to 108 particles/cm2/s. No events were observed on the standard Cardinal640 sensor at target fluences between 1.00E+10 to 1.00E+11 particles/cm2. FPGAs did not show any susceptibility to TNID at fluences up to 1.00E+11 (particles/cm2)

Risdiplam in Type 1 Spinal Muscular Atrophy

BACKGROUND: Type 1 spinal muscular atrophy is a rare, progressive neuromuscular disease that is caused by low levels of functional survival of motor neuron (SMN) protein. Risdiplam is an orally administered, small molecule that modifies SMN2 pre-messenger RNA splicing and increases levels of functional SMN protein. METHODS: We report the results of part 1 of a two-part, phase 2-3, open-label study of risdiplam in infants 1 to 7 months of age who had type 1 spinal muscular atrophy, which is characterized by the infant not attaining the ability to sit without support. Primary outcomes were safety, pharmacokinetics, pharmacodynamics (including the blood SMN protein concentration), and the selection of the risdiplam dose for part 2 of the study. Exploratory outcomes included the ability to sit without support for at least 5 seconds. RESULTS: A total of 21 infants were enrolled. Four infants were in a low-dose cohort and were treated with a final dose at month 12 of 0.08 mg of risdiplam per kilogram of body weight per day, and 17 were in a high-dose cohort and were treated with a final dose at month 12 of 0.2 mg per kilogram per day. The baseline median SMN protein concentrations in blood were 1.31 ng per milliliter in the low-dose cohort and 2.54 ng per milliliter in the high-dose cohort; at 12 months, the median values increased to 3.05 ng per milliliter and 5.66 ng per milliliter, respectively, which represented a median of 3.0 times and 1.9 times the baseline values in the low-dose and high-dose cohorts, respectively. Serious adverse events included pneumonia, respiratory tract infection, and acute respiratory failure. At the time of this publication, 4 infants had died of respiratory complications. Seven infants in the high-dose cohort and no infants in the low-dose cohort were able to sit without support for at least 5 seconds. The higher dose of risdiplam (0.2 mg per kilogram per day) was selected for part 2 of the study. CONCLUSIONS: In infants with type 1 spinal muscular atrophy, treatment with oral risdiplam led to an increased expression of functional SMN protein in the blood. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT02913482.)

Minimizing plasma temperature for antimatter mixing experiments

The ASACUSA collaboration produces a beam of antihydrogen atoms by mixing pure positron and antiproton plasmas in a strong magnetic field with a double cusp geometry. The positrons cool via cyclotron radiation inside the cryogenic trap. Low positron temperature is essential for increasing the fraction of antihydrogen atoms which reach the ground state prior to exiting the trap. Many experimental groups observe that such plasmas reach equilibrium at a temperature well above the temperature of the surrounding electrodes. This problem is typically attributed to electronic noise and plasma expansion, which heat the plasma. The present work reports anomalous heating far beyond what can be attributed to those two sources. The heating seems to be a result of the axially open trap geometry, which couples the plasma to the external (300 K) environment via microwave radiation

COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases

Although most autoimmune diseases are considered to be CD4 T cell- or antibody-mediated, many respond to CD20-depleting antibodies that have limited influence on CD4 and plasma cells. This includes rituximab, oblinutuzumab and ofatumumab that are used in cancer, rheumatoid arthritis and off-label in a large number of other autoimmunities and ocrelizumab in multiple sclerosis. Recently, the COVID-19 pandemic created concerns about immunosuppression in autoimmunity, leading to cessation or a delay in immunotherapy treatments. However, based on the known and emerging biology of autoimmunity and COVID-19, it was hypothesised that while B cell depletion should not necessarily expose people to severe SARS-CoV-2-related issues, it may inhibit protective immunity following infection and vaccination. As such, drug-induced B cell subset inhibition, that controls at least some autoimmunities, would not influence innate and CD8 T cell responses, which are central to SARS-CoV-2 elimination, nor the hypercoagulation and innate inflammation causing severe morbidity. This is supported clinically, as the majority of SARS-CoV-2-infected, CD20-depleted people with autoimmunity have recovered. However, protective neutralizing antibody and vaccination responses are predicted to be blunted until naive B cells repopulate, based on B cell repopulation kinetics and vaccination responses, from published rituximab and unpublished ocrelizumab (NCT00676715, NCT02545868) trial data, shown here. This suggests that it may be possible to undertake dose interruption to maintain inflammatory disease control, while allowing effective vaccination against SARS-CoV-29, if and when an effective vaccine is available