Beryllium global erosion and deposition at JET-ILW simulated with ERO2.0

The recently developed Monte-Carlo code ERO2.0 is applied to the modelling of limited and diverted discharges at JET with the ITER-like wall (ILW). The global beryllium (Be) erosion and deposition is simulated and compared to experimental results from passive spectroscopy. For the limiter configuration, it is demonstrated that Be self-sputtering is an important contributor (at least 35%) to the Be erosion. Taking this contribution into account, the ERO2.0 modelling confirms previous evidence that high deuterium (D) surface concentrations of up to similar to 50% atomic fraction provide a reasonable estimate of Be erosion in plasma-wetted areas. For the divertor configuration, it is shown that drifts can have a high impact on the scrape-off layer plasma flows, which in turn affect global Be transport by entrainment and lead to increased migration into the inner divertor. The modelling of the effective erosion yield for different operational phases (ohmic, L- and H-mode) agrees with experimental values within a factor of two, and confirms that the effective erosion yield decreases with increasing heating power and confinement.EURATOM 63305

Recent progress of plasma exhaust concepts and divertor designs for tokamak DEMO reactors

The power exhaust concept and an appropriate divertor design are common critical issues for tokamak DEMO design activities which have been carried out in Europe, Japan, China, Korea and the USA. Conventional divertor concepts and power exhaust studies for recent DEMO designs (Pfusion = 1 – 2 GW, Rp = 7 – 9 m) are reviewed from the viewpoints of the plasma physics issues and the divertor engineering design. Radiative cooling is a common approach for the power fusion scenario. Requirements on the main plasma radiation fraction (frad main = Prad main/Pheat) and the plasma performance constrain the divertor design concept. Different challenges contribute to optimizing the future DEMO designs: for example, (i) increasing the main plasma radiation fraction for ITER level Psep/Rp designs and simplifying the divertor geometry, and (ii) extending ITER divertor geometry with increasing divertor radiation (Prad div) for larger Psep/Rp ≥ 25MWm− 1 designs. Power exhaust simulations with large Psep = 150 – 300 MW have been performed using integrated divertor codes considering an ITER-based divertor geometry with longer leg length (1.6 – 1.7 m), as in a common baseline design. Geometry effects (ITER like geometry or more open one without baffle) on the plasma detachment profile and the required divertor radiation fraction (frad div = Prad div/Psep) were key aspects of these studies. All simulations showed that the divertor plasma detachment were extended widely across the target plate with a reduction in the peak heat load of qtarget ≤ 10 MWm− 2 for the large frad div = 0.7 – 0.8, while the peak qtarget location and value were noticeably different in the partially detached divertor. Simulation results also demonstrated that radial diffusion coefficients of the heat and particle fluxes were critical parameters for DEMO divertor design, and that effects of plasma drifts on outboard enhanced asymmetry of the heat flux, suggested the need for longer divertor leg to ensure the existence of a detached divertor operation with qtarget ≤ 10 MWm− 2 . Integrated design of the water cooled divertor target, cassette body (CB) and cooling pipe routing has been developed for each DEMO concept, based on the ITER-like tungsten monoblock (W-MB) with Cu-alloy cooling pipes. Engineering design adequate under higher neutron irradiation condition was required. Therefore, inlet coolant temperature (Tcool) was increased. In current designs, it still shows a large potential variation between 70 ◦C and 200 ◦C. The influence of thermal softening on the Cu-alloy (CuCrZr) pipe was fostered near the strike point when the high qtarget of ~10 MWm− 2 was studied. Improved technologies for high heat flux components based on the ITER W-MB unit have been developed for EU-DEMO. Different coolant conditions (low- and high Tcool) were provided for Cu-alloy and reduced activation ferritic martensitic (RAFM) steel heat sink units, respectively. The high-Tcool coolant was also considered for the CB and supporting structures. Appropriate conditions for the high-Tcool coolant, i.e. 180 ◦C/ 5 MPa (EU-DEMO) and 290 ◦C/ 15 MPa (JA-DEMO, CFETR and K-DEMO), will be determined in the future optimizations of the divertor and DEMO design

Estrogen regulation of mammary gland development and breast cancer: amphiregulin takes center stage

Estrogen-mediated proliferation is fundamental to normal mammary gland development. Recent studies have demonstrated that amphiregulin is a critical paracrine regulator of estrogen action during ductal morphogenesis. These studies implicate a critical role for amphiregulin in mammary stem cell differentiation as well as breast cancer initiation and progression

Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes.

A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM-receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes, including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). There is some evidence that these ECM cues affect one or more of the following processes: cell survival, polarity, proliferation, differentiation, adhesion, and migration. Both three-dimensional culture models and genetic manipulations of the mouse mammary gland have been used to study the signaling pathways that affect these processes. However, the precise mechanisms of ECM-directed mammary morphogenesis are not well understood. Mammary morphogenesis involves epithelial 'invasion' of adipose tissue, a process akin to invasion by breast cancer cells, although the former is a highly regulated developmental process. How these morphogenic pathways are integrated in the normal gland and how they become dysregulated and subverted in the progression of breast cancer also remain largely unanswered questions

EUROfusion-theory and advanced simulation coordination (E-TASC) : programme and the role of high performance computing

This paper is a written summary of an overview oral presentation given at the 1st Spanish Fusion High Performance Computer (HPC) Workshop that took place on the 27 November 2020 as an online event. Given that over the next few years ITER24 will move to its operation phase and the European-DEMO design will be significantly advanced, the EUROfusion consortium has initiated a coordination effort in theory and advanced simulation to address some of the challenges of the fusion research in Horizon EUROPE (2021-2027), i.e. the next EU Framework Programme for Research and Technological Development. This initiative has been called E-TASC, which stands for EUROfusion-Theory and Advanced Simulation Coordination. The general and guiding principles of E-TASC are summarized in this paper. In addition, an overview of the scientific results obtained in the pilot phase (2019-2020) of E-TASC are provided while highlighting the importance of the required progress in computational methods and HPC techniques. In the initial phase, five pilot theory and simulation tasks were initiated: towards a validated predictive capability of the low to high transition and pedestal physics; runaway electrons in tokamak disruptions in the presence of massive material injection; fast code for the calculation of neoclassical toroidal viscosity in stellarators and tokamaks; development of a neutral gas kinetics modular code; European edge and boundary code for reactor-relevant devices. In this paper, we report on recent progress made by each of these projects.Peer reviewe

A longitudinal study of olfactory dysfunction and parosmia in mild COVID-19 cases

Background: COVID-19-related olfactory dysfunction (OD) can persist long after patients recover from acute infection, yet few studies have investigated the long-term progression of this complication. Moreover, existing studies are focused on hyposmia/anosmia but parosmia is becoming an increasingly recognized long-term symptom. Methods: We completed a longitudinal study about OD in individuals with mild cases of COVID-19. Participants completed a questionnaire and Brief Smell Identification Test (BSIT) one week, one month and one year after diagnosis. At one-year, participants completed an additional survey about parosmia. Results: We obtained questionnaires and psychophysical olfactory testing information from participants at one week (n=45), one month (n=38), and one year (n=33) post COVID-19 diagnosis. At one-year, 15.2% of participants had persistent OD and 66.7% of participants reported experiencing parosmia at some point following COVID-19 diagnosis. The mean onset of parosmia was 1.3 weeks (SD: 1.9 weeks) after diagnosis, although two patients reported delayed onset (>4 weeks after diagnosis). Eight patients (24.2%) reported ongoing parosmia one year after diagnosis. Of the patients whose parosmia resolved, the mean duration of symptoms was 7.2 weeks (SD: 7.3 weeks). Conclusion: Decreased sense of smell associated with COVID-19 infection has received significant recognition in both the media and in the medical literature. Symptoms of OD and parosmia were common in our patients with COVID-19. Hyposmia, anosmia, and parosmia, all decrease quality of life, necessitating continued research to understand the pathogenesis, course of symptoms, and possible treatment for these complications

First divertor physics studies in Wendelstein 7-X

The Wendelstein 7-X (W7-X) optimized stellarator fusion experiment, which went into operation in 2015, has been operating since 2017 with an un-cooled modular graphite divertor. This allowed first divertor physics studies to be performed at pulse energies up to 80 MJ, as opposed to 4 MJ in the first operation phase, where five inboard limiters were installed instead of a divertor. This, and a number of other upgrades to the device capabilities, allowed extension into regimes of higher plasma density, heating power, and performance overall, e.g. setting a new stellarator world record triple product. The paper focuses on the first physics studies of how the island divertor works. The plasma heat loads arrive to a very high degree on the divertor plates, with only minor heat loads seen on other components, in particular baffle structures built in to aid neutral compression. The strike line shapes and locations change significantly from one magnetic configuration to another, in very much the same way that codes had predicted they would. Strike-line widths are as large as 10 cm, and the wetted areas also large, up to about 1.5 m(2), which bodes well for future operation phases. Peak local heat loads onto the divertor were in general benign and project below the 10 MW m(-2) limit of the future water-cooled divertor when operated with 10 MW of heating power, with the exception of low-density attached operation in the high-iota configuration. The most notable result was the complete (in all 10 divertor units) heat-flux detachment obtained at high-density operation in hydrogen

Prognostic value of Dicer expression in human breast cancers and association with the mesenchymal phenotype

Background: Dicer, a ribonuclease, is the key enzyme required for the biogenesis of microRNAs and small interfering RNAs and is essential for both mammalian development and cell differentiation. Recent evidence indicates that Dicer may also be involved in tumourigenesis. However, no studies have examined the clinical significance of Dicer at both the RNA and the protein levels in breast cancer.Methods: In this study, the biological and prognostic value of Dicer expression was assessed in breast cancer cell lines, breast cancer progression cellular models, and in two well-characterised sets of breast carcinoma samples obtained from patients with long-term follow-up using tissue microarrays and quantitative reverse transcription-PCR.Results: We have found that Dicer protein expression is significantly associated with hormone receptor status and cancer subtype in breast tumours (ER P=0.008; PR P=0.019; cancer subtype P=0.023, luminal A P=0.0174). Dicer mRNA expression appeared to have an independent prognostic impact in metastatic disease (hazard ratio=3.36, P=0.0032). In the breast cancer cell lines, lower Dicer expression was found in cells harbouring a mesenchymal phenotype and in metastatic bone derivatives of a breast cancer cell line. These findings suggest that the downregulation of Dicer expression may be related to the metastatic spread of tumours.Conclusion: Assessment of Dicer expression may facilitate prediction of distant metastases for patients suffering from breast cancer

COVID-19 related olfactory dysfunction prevalence and natural history in ambulatory patients

Background: Evidence regarding prevalence of COVID-19 related Olfactory dysfunction (OD) among ambulatory patients is highly variable due to heterogeneity in study population and measurement methods. Relatively few studies have longitudinally investigated OD in ambulatory patients with objective methods. Methods: We performed a longitudinal study to investigate OD among COVID-19 ambulatory patients compared to symptomatic controls who test negative. Out of 81 patients enrolled, 45 COVID-19 positive patients and an age- and sex-matched symptomatic control group completed the BSIT and a questionnaire about smell, taste and nasal symptoms. These were repeated at 1 month for all COVID-19 positive patients, and again at 3 months for those who exhibited persistent OD. Analysis was performed by mixed-effects linear and logistic regression. Results: 46.7% of COVID-19 patients compared to 3.8% of symptomatic controls exhibited OD at 1-week post diagnosis (p<0.001). At 1 month, 16.7%, (6 of 36), of COVID-19 patients had persistent OD. Mean improvement in BSIT score in COVID-19 patients between 1-week BSIT and 1 month follow-up was 2.0 (95% CI 1.00 – 3.00, p<0.001). OD did not correlate with nasal congestion (r= −0.25, 95% CI, −0.52 to 0.06, p=0.12). Conclusions: Ambulatory COVID-19 patients exhibited OD significantly more frequently than symptomatic controls. Most patients regained normal olfaction by 1 month. The BSIT is a simple validated and objective test to investigate the prevalence of OD in ambulatory patients. OD did not correlate with nasal congestion which suggests a congestion-independent mechanism of OD