Upgrade of the ultracold neutron source at the pulsed reactor TRIGA Mainz

The performance of the upgraded solid deuterium ultracold neutron source at the pulsed reactor TRIGA Mainz is described. The current configuration stage comprises the installation of a He liquefier to run UCN experiments over long-term periods, the use of stainless steel neutron guides with improved transmission as well as sputter-coated non-magnetic $^{58}$NiMo alloy at the inside walls of the thermal bridge and the converter cup. The UCN yield was measured in a `standard' UCN storage bottle (stainless steel) with a volume of 32 litres outside the biological shield at the experimental area yielding UCN densities of 8.5 /cm$^3$; an increase by a factor of 3.5 compared to the former setup. The measured UCN storage curve is in good agreement with the predictions from a Monte Carlo simulation developed to model the source. The growth and formation of the solid deuterium converter during freeze-out are affected by the ortho/para ratio of the H$_2$ premoderator.Comment: 12 pages, 7 figure

SIMON: A Digital Protocol to Monitor and Predict Suicidal Ideation

Each year, more than 800,000 persons die by suicide, making it a leading cause of death worldwide. Recent innovations in information and communication technology may offer new opportunities in suicide prevention in individuals, hereby potentially reducing this number. In our project, we design digital indices based on both self-reports and passive mobile sensing and test their ability to predict suicidal ideation, a major predictor for suicide, and psychiatric hospital readmission in high-risk individuals: psychiatric patients after discharge who were admitted in the context of suicidal ideation or a suicidal attempt, or expressed suicidal ideations during their intake. Specifically, two smartphone applications -one for self-reports (SIMON-SELF) and one for passive mobile sensing (SIMON-SENSE)- are installed on participants' smartphones. SIMON-SELF uses a text-based chatbot, called Simon, to guide participants along the study protocol and to ask participants questions about suicidal ideation and relevant other psychological variables five times a day. These self-report data are collected for four consecutive weeks after study participants are discharged from the hospital. SIMON-SENSE collects behavioral variables -such as physical activity, location, and social connectedness- parallel to the first application. We aim to include 100 patients over 12 months to test whether (1) implementation of the digital protocol in such a high-risk population is feasible, and (2) if suicidal ideation and psychiatric hospital readmission can be predicted using a combination of psychological indices and passive sensor information. To this end, a predictive algorithm for suicidal ideation and psychiatric hospital readmission using various learning algorithms (e.g., random forest and support vector machines) and multilevel models will be constructed. Data collected on the basis of psychological theory and digital phenotyping may, in the future and based on our results, help reach vulnerable individuals early and provide links to just-in-time and cost-effective interventions or establish prompt mental health service contact. The current effort may thus lead to saving lives and significantly reduce economic impact by decreasing inpatient treatment and days lost to inability

Long-term trends of black carbon and particle number concentration in the lower free troposphere in Central Europe

Background: The implementation of emission mitigation policies in Europe over the last two decades has generally improved the air quality, which resulted in lower aerosol particle mass, particle number, and black carbon mass concentration. However, little is known whether the decreasing particle concentrations at a lower-altitude level can be observed in the free troposphere (FT), an important layer of the atmosphere, where aerosol particles have a longer lifetime and may affect climate dynamics. In this study, we used data from two high-Alpine observatories, Zugspitze-Schneefernerhaus (ZSF) and Jungfraujoch (JFJ), to assess the long-term trends on size-resolved particle number concentrations (PNCs) and equivalent black carbon (eBC) mass concentration separated for undisturbed lower FT conditions and under the influence of air from the planetary boundary layer (PBL) from 2009 to 2018. Results: The FT and PBL-influenced conditions were segregated for both sites. We found that the FT conditions in cold months were more prevalent than in warm months, while the measured aerosol parameters showed different seasonal patterns for the FT and PBL-influenced conditions. The pollutants in the PBL-influenced condition have a higher chance to be transported to high-altitudes due to the mountainous topography, leading to a higher concentration and more distinct seasonal variation, and vice versa. The long-term trends of the measured aerosol parameters were evaluated and the decreased aerosol concentrations were observed for both FT and PBL-influenced conditions. The observed decreasing trends in eBC concentration in the PBL-influenced condition are well consistent with the reported trends in total BC emission in Germany and Switzerland. The decreased concentrations in the FT condition suggest that the background aerosol concentration in the lower FT over Central Europe has correspondingly decreased. The change of back trajectories in the FT condition at ZSF and JFJ was further evaluated to investigate the other possible drivers for the decreasing trends. Conclusions: The background aerosol concentration in the lower FT over Central Europe has significantly decreased during 2009–2018. The implementation of emission mitigation policies is the most decisive factor and the decrease of the regional airmass occurrence over Central Europe also has contributed to the decreasing trends. © 2021, The Author(s)

A20 regulates lymphocyte adhesion in murine neuroinflammation by restricting endothelial ICOSL expression in the CNS.

A20 is a ubiquitin-modifying protein that negatively regulates NF-κB signaling. Mutations in A20/TNFAIP3 are associated with a variety of autoimmune diseases, including multiple sclerosis (MS). We found that deletion of A20 in central nervous system (CNS) endothelial cells (ECs) enhances experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. A20∆CNS-EC mice showed increased numbers of CNS-infiltrating immune cells during neuroinflammation and in the steady state. While the integrity of the blood-brain barrier (BBB) was not impaired, we observed a strong activation of CNS-ECs in these mice, with dramatically increased levels of the adhesion molecules ICAM-1 and VCAM-1. We discovered ICOSL as adhesion molecule expressed by A20-deficient CNS-ECs. Silencing of ICOSL in CNS microvascular ECs partly reversed the phenotype of A20∆CNS-EC mice without reaching statistical significance and delayed the onset of EAE symptoms in wildtype mice. In addition, blocking of ICOSL on primary mouse brain microvascular endothelial cells (pMBMECs) impaired the adhesion of T cells in vitro. Taken together, we here propose that CNS EC-ICOSL contributes to the firm adhesion of T cells to the BBB, promoting their entry into the CNS and eventually driving neuroinflammation

Analysis of expression profiles of MAGE-A antigens in oral squamous cell carcinoma cell lines

<p>Abstract</p> <p>Background</p> <p>The immunological response to solid tumours is insufficient. Therefore, tumour specific antigens have been explored to facilitate the activation of the immune system. The cancer/testis antigen class of MAGE-A antigens is a possible target for vaccination. Their differential expression profiles also modulate the course of the cancer disease and its response to antineoplastic drugs.</p> <p>Methods</p> <p>The expression profiles of MAGE-A2, -A3, -A4, -A6 and -A10 in five own oral squamous cell carcinoma cell lines were characterised by rt-PCR, qrt-PCR and immunocytochemistry with a global MAGE-A antibody (57B) and compared with those of an adult keratinocyte cell line (NHEK).</p> <p>Results</p> <p>All tumour cell lines expressed MAGE-A antigens. The antigens were expressed in groups with different preferences. The predominant antigens expressed were MAGE-A2, -A3 and -A6. MAGE-A10 was not expressed in the cell lines tested. The MAGE-A gene products detected in the adult keratinocyte cell line NHEK were used as a reference.</p> <p>Conclusion</p> <p>MAGE-A antigens are expressed in oral squamous cell carcinomas. The expression profiles measured facilitate distinct examinations in forthcoming studies on responses to antineoplastic drugs or radiation therapy. MAGE-A antigens are still an interesting aim for immunotherapy.</p

Volume versus standard coils in the treatment of intracranial aneurysms

Background Volume coils were developed to improve occlusion rates of intracranial aneurysms. Previous studies have shown increased packing density and comparable occlusion rates, but subgroup analyses of aneurysm size have not been carried out. Objective To evaluate the safety and efficacy of the Penumbra Coil 400 (PC400) system in treating intracranial aneurysms compared with standard diameter coils. Methods A monocentric retrospective case review of 260 aneurysms in 233 patients was carried out. In 37 aneurysms the PC400 system was used, while 223 aneurysms were treated with conventional coils. Previously treated aneurysms and aneurysms treated with flow diverters were excluded. Aneurysm and procedure characteristics, packing density, postprocedural and follow-up occlusion grades as well as coil compaction were evaluated. Results Aneurysms treated with PC400 coils had higher volume (218.9 vs 47.1mm(3), p<0.001), wider necks (3.0 vs 2.5mm, p=0.005), and greater dome/neck ratio (2.0 vs 1.6, p=0.001) in comparison with aneurysms treated with conventional coils. Compared with controls, in the PC400 group we achieved higher packing densities (43.2% vs 34.4%, p<0.001;in aneurysms 7mm 42.2% vs 27.8%, p<0.001). On follow-up angiography we observed less coil compaction (23.8% vs 64.3%, p=0.003) and less aneurysm recurrence (14.3% vs 40.5%, p=0.046) in aneurysms 7mm when using the PC400 system. Conclusions Use of the PC400 system as opposed to conventional coils suggests that the PC400 system is safe and effective in treating intracranial aneurysms. Despite having been applied in a potentially more difficult-to-treat group, the use of PC400 was associated with less coil compaction and aneurysm recurrence in aneurysms 7mm

Cellulose and callose synthesis and organization in focus, what's new?

Plant growth and development are supported by plastic but strong cell walls. These walls consist largely of polysaccharides that vary in content and structure. Most of the polysaccharides are produced in the Golgi apparatus and are then secreted to the apoplast and built into the growing walls. However, the two glucan polymers cellulose and callose are synthesized at the plasma membrane by cellulose or callose synthase complexes, respectively. Cellulose is the most common cell wall polymer in land plants and provides strength to the walls to support directed cell expansion. In contrast, callose is integral to specialized cell walls, such as the cell plate that separates dividing cells and growing pollen tube walls, and maintains important functions during abiotic and biotic stress responses. The last years have seen a dramatic increase in our understanding of how cellulose and callose are manufactured, and new factors that regulate the synthases have been identified. Much of this knowledge has been amassed via various microscopy-based techniques, including various confocal techniques and super-resolution imaging. Here, we summarize and synthesize recent findings in the fields of cellulose and callose synthesis in plant biology

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study

Background The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. Methods OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Results Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. Conclusions Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. Trial registration Registered in July 2016 at clinicaltrials.gov (NCT02847442)