Anisotropic Radio-Wave Scattering and the Interpretation of Solar Radio Emission Observations

The observed properties (i.e., source size, source position, time duration, decay time) of solar radio emission produced through plasma processes near the local plasma frequency, and hence the interpretation of solar radio bursts, are strongly influenced by propagation effects in the inhomogeneous turbulent solar corona. In this work, a 3D stochastic description of the propagation process is presented, based on the Fokker-Planck and Langevin equations of radio-wave transport in a medium containing anisotropic electron density fluctuations. Using a numerical treatment based on this model, we investigate the characteristic source sizes and burst decay times for Type III solar radio bursts. Comparison of the simulations with the observations of solar radio bursts shows that predominantly perpendicular density fluctuations in the solar corona are required, with an anisotropy factor ~0.3 for sources observed at around 30 MHz. The simulations also demonstrate that the photons are isotropized near the region of primary emission, but the waves are then focused by large-scale refraction, leading to plasma radio emission directivity that is characterized by a half-width-half-maximum of about 40 degrees near 30 MHz. The results are applicable to various solar radio bursts produced via plasma emission

Loss of the mammal-specific tectorial membrane component CEA cell adhesion molecule 16 (CEACAM16) leads to hearing impairment at low and high frequencies

The vertebrate-restricted carcinoembryonic antigen gene family evolves extremely rapidly. Among their widely expressed members, the mammal-specific, secreted CEACAM16 is exceptionally well conserved and specifically expressed in the inner ear. To elucidate a potential auditory function we inactivated murine Ceacam16 by homologous recombination. In young Ceacam16-/- mice the hearing threshold for frequencies below 10 kHz and above 22 kHz was raised. This hearing impairment progressed with age. A similar phenotype is observed in hearing-impaired members of Family 1070 with non-syndromic autosomal dominant hearing loss (DFNA4) who carry a missense mutation in CEACAM16. CEACAM16 was found in interdental and Deiters cells and was deposited in the tectorial membrane of the cochlea between postnatal day 12 and 15, when hearing starts in mice. In cochlear sections of Ceacam16-/- mice tectorial membranes were significantly more often stretched out as compared to wild-type mice where they were mostly contracted and detached from the outer hair cells. Homotypic cell sorting observed after ectopic cell surface expression of the carboxy-terminal immunoglobulin variable-like N2 domain of CEACAM16 indicated that CEACAM16 can interact in trans. Furthermore, Western blot analyses of membrane-bound CEACAM16 under reducing and non-reducing conditions demonstrated oligomerization via unpaired cysteines. Taken together, CEACAM16 probably can form higher order structures with other tectorial membrane proteins such as α-tectorin and β-tectorin and influences the physical properties of the tectorial membrane. Evolution of CEACAM16 might have been an important step for the specialization of the mammalian cochlea allowing hearing over an extended frequency range

Performance of Different Diagnostic PD-L1 Clones in Head and Neck Squamous Cell Carcinoma

Background: The approval of immune checkpoint inhibitors in combination with specific diagnostic biomarkers presents new challenges to pathologists as tumor tissue needs to be tested for expression of programmed death-ligand 1 (PD-L1) for a variety of indications. As there is currently no requirement to use companion diagnostic assays for PD-L1 testing in Germany different clones are used in daily routine. While the correlation of staining results has been tested in various entities, there is no data for head and neck squamous cell carcinomas (HNSCC) so far. Methods: We tested five different PD-L1 clones (SP263, SP142, E1L3N, 22-8, 22C3) on primary HNSCC tumor tissue of 75 patients in the form of tissue microarrays. Stainings of both immune and tumor cells were then assessed and quantified by pathologists to simulate real-world routine diagnostics. The results were analyzed descriptively and the resulting staining pattern across patients was further investigated by principal component analysis and non-negative matrix factorization clustering. Results: Percentages of positive immune and tumor cells varied greatly. Both the resulting combined positive score as well as the eligibility for certain checkpoint inhibitor regimens was therefore strongly dependent on the choice of the antibody. No relevant co-clustering and low similarity of relative staining patterns across patients was found for the different antibodies. Conclusions: Performance of different diagnostic anti PD-L1 antibody clones in HNSCC is less robust and interchangeable compared to reported data from other tumor entities. Determination of PD-L1 expression is critical for therapeutic decision making and may be aided by back-to-back testing of different PD-L1 clones

BAP1 germline mutation in two first grade family members with uveal melanoma

Background: Uveal melanoma (UM) is the most common primary cancer of the eye in adults. About half of the patients are at risk of developing metastatic disease resulting in a poor clinical prognosis. Metastatic progression is strongly associated with loss of one chromosome 3 in the tumour (monosomy 3). The tumour suppressor gene BAP1 was found to be recurrently mutated in UM with monosomy 3. Familial UM is rare and amounts to about 0.6–6% of all patients with melanoma. However, BAP1 germline mutations have been identified in rare hereditary tumour syndromes, including cases with UM. One may assume that UM may be part of these hereditary conditions with predisposition to malignant cancers. Methods: The patients underwent complete ophthalmological workup and enucleation due to UM. Microsatellite analysis was performed to determine the chromosome 3 status of the tumours. Sanger sequencing of all coding exons of the BAP1 gene was performed in blood DNA of the patients. Results: Here we report on two family members (mother and son) diagnosed with UM. In both patients, a cosegregating BAP1 germline mutation (c.299 T>C) was found. The mutant BAP1 allele was retained in the tumour of the son showing monosomy 3. The son further developed urothelial carcinoma and liver metastasis, the mother was affected by the UM and cholangiocellular carcinoma. Conculsions: We detected a cosegregating BAP1 germline mutation in two family members with UM. This suggests that, consistent with a classic tumour suppressor model, carriers of damaging mutations in BAP1 are predisposed to UM. However, as BAP1 germline mutations have been found to cause other cancer syndromes as well, there must be other factors that decide about the type of tumour emerging from BAP1 inactivation

First near-relativistic solar electron events observed by EPD onboard Solar Orbiter

Context. Solar Orbiter, launched in February 2020, started its cruise phase in June 2020, in coincidence with its first perihelion at 0.51 au from the Sun. The in situ instruments onboard, including the Energetic Particle Detector (EPD), operate continuously during the cruise phase enabling the observation of solar energetic particles. Aims. In situ measurements of the first near-relativistic solar electron events observed in July 2020 by EPD are analyzed and the solar origins and the conditions for the interplanetary transport of these particles investigated. Methods. Electron observations from keV energies to the near-relativistic range were combined with the detection of type III radio bursts and extreme ultraviolet (EUV) observations from multiple spacecraft in order to identify the solar origin of the electron events. Electron anisotropies and timing as well as the plasma and magnetic field environment were evaluated to characterize the interplanetary transport conditions. Results. All electron events were clearly associated with type III radio bursts. EUV jets were also found in association with all of them except one. A diversity of time profiles and pitch-angle distributions was observed. Different source locations and different magnetic connectivity and transport conditions were likely involved. The July 11 event was also detected by Wind, separated 107 degrees in longitude from Solar Orbiter. For the July 22 event, the Suprathermal Electron and Proton (STEP) sensor of EPD allowed for us to not only resolve multiple electron injections at low energies, but it also provided an exceptionally high pitch-angle resolution of a very anisotropic beam. This, together with radio observations of local Langmuir waves suggest a very good magnetic connection during the July 22 event. This scenario is challenged by a high-frequency occultation of the type III radio burst and a nominally non-direct connection to the source; therefore, magnetic connectivity requires further investigation

MAGE expression in head and neck squamous cell carcinoma primary tumors, lymph node metastases and respective recurrences-implications for immunotherapy

Melanoma associated antigens (MAGE) are potential targets for immunotherapy and have been associated with poor overall survival (OS) in head and neck squamous cell carcinoma (HNSCC). However, little is known about MAGE in lymph node metastases (LNM) and recurrent disease (RD) of HNSCC. To assess whether MAGE expression increases with metastasis or recurrence, a tissue microarray (TMA) of 552 primary tumors (PT), 219 LNM and 75 RD was evaluated by immunohistochemistry for MAGE antigens using three monoclonal antibodies to multiple MAGE family members. Mean expression intensity (MEI) was obtained from triplicates of each tumor specimen. The median MEI compared between PT, LNM and RD was significantly higher in LNM and RD. In paired samples, MEI was comparable in PT to respective LNM, but significantly different from RD. Up to 25% of patients were negative for pan-MAGE or MAGE-A3/A4 in PT, but positive in RD. The prognostic impact of MAGE expression was validated in the TMA cohort and also in TCGA data (mRNA). OS was significantly lower for patients expressing pan-MAGE or MAGE-A3/A4 in both independent cohorts. MAGE expression was confirmed as a prognostic marker in HNSCC and may be important for immunotherapeutic strategies as a shared antigen

Erratum: “Spectral Analysis of Solar Radio Type III Bursts from 20 kHz to 410 MHz” (2022, ApJ, 924, 58)

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Modeling observations of solar coronal mass ejections with heliospheric imagers verified with the Heliophysics System Observatory

We present an advance toward accurately predicting the arrivals of coronal mass ejections (CMEs) at the terrestrial planets, including Earth. For the first time, we are able to assess a CME prediction model using data over two thirds of a solar cycle of observations with the Heliophysics System Observatory. We validate modeling results of 1337 CMEs observed with the Solar Terrestrial Relations Observatory (STEREO) heliospheric imagers (HI) (science data) from 8 years of observations by five in situ observing spacecraft. We use the self-similar expansion model for CME fronts assuming 60 degrees longitudinal width, constant speed, and constant propagation direction. With these assumptions we find that 23%-35% of all CMEs that were predicted to hit a certain spacecraft lead to clear in situ signatures, so that for one correct prediction, two to three false alarms would have been issued. In addition, we find that the prediction accuracy does not degrade with the HI longitudinal separation from Earth. Predicted arrival times are on average within 2.6 +/- 16.6 h difference of the in situ arrival time, similar to analytical and numerical modeling, and a true skill statistic of 0.21. We also discuss various factors that may improve the accuracy of space weather forecasting using wide-angle heliospheric imager observations. These results form a first-order approximated baseline of the prediction accuracy that is possible with HI and other methods used for data by an operational space weather mission at the Sun-Earth L5 point. Plain Language Summary Solar storms are formed by incredibly powerful explosions on the Sun and travel as clouds of plasma threaded by magnetic fields through the solar system. Depending on their propagation direction, they may impact planets such as Earth, where they elicit colorful aurorae or, in very seldom cases, can lead to power failures with potentially tremendous economical and societal effects, thus posing a serious natural hazard. In this work, we have shown how well the solar storm impact can be forecasted when using a special type of instrument that can actually image the solar storms as they propagate toward the planets and even as they sweep over them. Our analysis includes two thirds of a solar cycle with 8 years of data, and spacecraft at Mercury, Venus, Earth, and in the solar wind to check on the correctness of our predictions. We could forecast the arrival time within +/- 16 h, and for one correct impact there are two to three false alarms. This forms a new baseline for the science of space weather prediction. Clearly, the modeling should be further improved to be used on a daily basis for a space weather mission to the Sun-Earth L5 point.Peer reviewe

Terrain, politics, history

This article is based on the 2019 Dialogues in Human Geography plenary lecture at the Royal Geographical Society. It has four parts. The first discusses my work on territory in relation to recent work by geographers and others on the vertical, the volumetric, the voluminous, and the milieu as ways of thinking space in three-dimensions, of a fluid and dynamic earth. Second, it proposes using the concept of terrain to analyse the political materiality of territory. Third, it adds some cautions to this, through thinking about the history of the concept of terrain in geographical thought, which has tended to associate it with either physical or military geography. Finally, it suggests that this work is a way geographers might begin to respond to the challenge recently made by Bruno Latour, where he suggests that ‘belonging to a territory is the phenomenon most in need of rethinking and careful redescription; learning new ways to inhabit the Earth is our biggest challenge’. Responding to Latour continues this thinking about the relations between territory, Earth, land, and ground, and their limits