Magnetic properties of a long-lived sunspot - Vertical magnetic field at the umbral boundary

Context. In a recent statistical study of sunspots in 79 active regions, the vertical magnetic field component $B_\text{ver}$ averaged along the umbral boundary is found to be independent of sunspot size. The authors of that study conclude that the absolute value of $B_\text{ver}$ at the umbral boundary is the same for all spots. Aims. We investigate the temporal evolution of $B_\text{ver}$ averaged along the umbral boundary of one long-lived sunspot during its stable phase. Methods. We analysed data from the HMI instrument on-board SDO. Contours of continuum intensity at $I_\text{c}=0.5I_\text{qs}$, whereby $I_\text{qs}$ refers to the average over the quiet sun areas, are used to extract the magnetic field along the umbral boundary. Projection effects due to different formation heights of the Fe I 617.3 nm line and continuum are taken into account. To avoid limb artefacts, the spot is only analysed for heliocentric angles smaller than $60^{\circ}$. Results. During the first disc passage, NOAA AR 11591, $B_\text{ver}$ remains constant at 1693 G with a root-mean-square deviation of 15 G, whereas the magnetic field strength varies substantially (mean 2171 G, rms of 48 G) and shows a long term variation. Compensating for formation height has little influence on the mean value along each contour, but reduces the variations along the contour when away from disc centre, yielding a better match between the contours of $B_\text{ver}=1693$ G and $I_\text{c}=0.5I_\text{qs}$. Conclusions. During the disc passage of a stable sunspot, its umbral boundary can equivalently be defined by using the continuum intensity $I_\text{c}$ or the vertical magnetic field component $B_\text{ver}$. Contours of fixed magnetic field strength fail to outline the umbral boundary.Comment: accepted for publication in A&A; v2 minor edit, correcting statement regarding one citatio

The Siglec-sialic acid axis is a target for innate immunotherapy of glioblastoma

In spite of the paradigm shift in cancer therapy that came with the discovery of immune checkpoint inhibitors, current treatment modalities which are predominantly T cell centric, fail to evoke durable tumor rejection in glioblastoma (GBM) patients. Leaving aside the fundamental role innate immune cells play in the tumor microen-vironment (TME), especially in less immunogenic tumors such as GBM. Upregulation of sialic acid-containing glycans on the cell surface and in the tumor microenvironment (hypersialylation) is a key change in malignant tissue and capable of impacting tumorigenesis by promoting cell invasion and metastatic po-tential. By engaging immunomodulatory sialic acid-binding immunoglobulin-like lectins (Siglecs), tumor hypersialylation can trigger tolerogenic programs in different immune cell types and contributes to the establishment of the immunosuppressive TME. By targeting inhibitory Siglec-E receptor on GBM-associated microglia (MG) and monocyte-derived cells (MdCs), we show increased tumor cell phagocytosis and improved subsequent T cell activation. Using a poorly immunogenic GBM pre-clinical model, we further demonstrate the synergistic potential of Siglec-E blockade in combined immunotherapies against GBM. Finally, we showcase the translational relevance of Siglec disruption on patient-derived samples. To explore other tolerogenic programs within the GBM immune TME on a single-cell level, we performed single-cell RNA sequencing (scRNA-seq) on paired biopsies from the tumor center, peripheral infiltration zone and blood of five primary GBM patients. We revealed a regionally distinct transcription profile of microglia (MG) and monocyte-derived macrophages (MdMs) and an impaired activation sig-nature in the tumor-peripheral cytotoxic-cell compartment. Comparing tumor-infiltrating CD8+ T cells with circulating cells identified CX3CR1high and CX3CR1int CD8+ T cells with effector and memory phenotype, respectively, enriched in blood but absent in the TME. Based on our data, we propose Siglec-E as innate immune checkpoint in GBM-associated MG and MdCs and underscore the value of Siglec blockade in lib-erating innate immune responses to potentiate anti-tumor immunity. Further, our scRNA-seq analysis provides a regionally-resolved mapping of transcriptional states in GBM-associated leukocytes, serving as an additional asset to the research community in their effort to uncover novel therapeutic strategies to combat this fatal disease

The contrasted evolution of cycling during youth. Determinants of bicycle ownership and use

Cycling during youth is characterized in many countries by two trends: its decline over the course of several decades (termed the generation effect) and its decline over the life course of individuals (the age effect). This paper addresses the age effect through a survey carried out among young people aged 12–20 (n = 1,358) in a Swiss city. It goes beyond the cyclist/non-cyclist dichotomy and identifies several cases in terms of skills (ability to ride a bike), access (ownership of a bike), and uses (reasons for and frequency of cycling). While most young people (98%) learned how to ride a bike as a child, an important minority do not continue cycling beyond childhood. Among those who continue, the use of the bike often changes over time to become less utilitarian and more recreational and occasional. The main determinants explaining cycling practices among young people are socialization (the parents’ cycling practices and level of education), gender, and the spaces of everyday life (place of residence and school). The results point to several levers to foster cycling among young people, to anchor sustainable mobility practices for years to come

Cytoprotection and healing: Two unequal brethren

The promotion of the concept of cytoprotection has fostered hopes that the use of co-prescribed mucosal protective agents would revolutionize the prevention of NSAID-induced ulcers and supply the basis for novel ulcer therapy. Prostaglandins do not, however, accelerate ulcer healing when applied at doses that exert an unequivocal cytoprotective activity. Attempts have therefore been made in recent years to create new less-toxic NSAIDs, such as combined lipoxygenase/cyclo-oxygenase inhibitors, NSAIDs coupled to an NO donor and so-called COX-2 inhibitors. All these preparations do in fact exert a diminished gastrointestinal toxicity. There is however increasing evidence accumulating from studies performed in and outside our laboratories that in chromic ulcer models their increased gastrointestinal tolerance is not necessarily reflected by non-interference with ulcer healing. It is thus mandatory to distinguish between cytoprotective and healing properties of drugs interfering with the cyclo-oxygenase pathwa

Combined Interventional Radiological and Endoscopical Approach for the Treatment of a Postoperative Biliary Stricture and Fistula

A 43-year old woman was admitted 11 days after open cholecystectomy with a iatrogenic bile duct injury. On admission the patient showed an uncontrolled biliary fistula through an external drain placed at an emergency laparotomy for biliary peritonitis with fever and jaundice. PTC showed a biliary stricture type II (Bismuth). A percutaneous drainage was performed to decompress the biliary system. Three weeks later, percutaneous balloon dilatation of the stricture was performed. However, bile leakage persisted. In a combined transhepatic/ endoscopic procedure, the percutaneous biliary drainage was replaced by a nasobiliary tube. One week later, no stricture was found and the biliary leak was sealed. The patient could be discharged without symptoms or signs of cholestasis. The multidisciplinary management of post-operative biliary fistula is presented, comparing the role of interventional radiology, endoscopy and surgery

Monooxygenase, epoxide hydrolase, and glutathione-S-transferase activities in human lung. Variation between groups of bronchogenic carcinoma and non-cancer patients and interindividual differences

Activities of microsomal monooxygenases (MO) and epoxide hydrolase (EH) and cytoplasmic glutathione-S-transferases (GST) will contribute to controlling the pool of reactive intermediates, enzymatically derived from polynuclear aromatic hydrocarbons (PAH) within the cells of target organs such as the human lung. Therefore, we studied what interindividual differences exist in these enzyme activities and whether there is a correlation between the activities of these epoxide forming and metabolizing enzymes in preparations from peripheral lung samples and the occurrence of bronchogenic carcinomas in smokers and non-smokers. 57 samples obtained from surgery were studied. Among them were 12 samples from non-smoking patients without cancer as a control group. It is not known whether this control group behaves, with respect to the investigated parameters, identically to fully healthy people, since in all cases indications existed which justified the removal of lung biopsies. Using very sensitive standard assays with benzo[a]pyrene, biphenyl, 7-ethoxyresorufin and 7-ethoxycoumarin as substrates, MO activity could only be determined as O-deethylation of 7-ethoxycoumarin and only after modification of the assay method. Evidence was obtained for the presence of a diffusible, but not dialyslble, MO Inhibitor in human lung microsomes. The MO activity (substrate: 7-ethoxycoumarin) in this fraction was extremely low in human (100-fold lower than in rat lung preparations), whereas EH (substrate: benzo[a]pyrene 4, 5-oxide) was slightly (about 2-fold) higher in human and GST (substrate: 2, 4-dinitrochlorobenzene) had similar activities in both species. Interindividual variations of enzyme activities in human lung were considerable: MO, 40-fold: EH, 5-fold; GST 10-fold. Compared to the control group (non-smokers without cancer) MO activities were slightly but significantly higher in lungs from bronchogenic carcinoma patients whether they were smokers (170% of controls, p 0.1) between the various groups studied. The substrate specificity of human lung EH, which was studied using five K-region epoxides of various PAH as substrates, corresponded to that in human and rat liver and in human, mouse and rat skin and to the pure enzyme isolated from rat liver. In contrast to rat liver hepatoma preparations, where EH had been shown to be increased in the tumor tissue and had been identified as a preneoplastic antigen, EH activity in lung microsomal preparations from samples of peripheral squamous cell carcinomas of two subjects had in the tumor tissue only one third of the activity of non-diseased areas of the same lun