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We have characterized the magnetization easy-axis of ultra-thin Co films (2–5 atomic layers, AL) grown on Ru(0001) when they are capped with a monolayer of Pd. The addition of a Pd monolayer turns the magnetization of 3 and 4 AL-thick Co films from an in-plane to an out-of-plane alignment, but not that of a 5 AL-thick film. These observations are explained in terms of an enhancement of the surface anisotropy. The exposure of the sample to hydrogen, CO or a combination of both gases does not overcome this effect.

Introduction Current ketamine-based therapies for treatment-resistant depression (TRD) often induce dissociative effects. A novel oral PR ketamine formulation (KET01) results in a low and delayed peak concentration of ketamine, high hydroxynorketamine concentration, and is associated with limited dissociative properties. Objectives To investigate efficacy, safety, and pharmacokinetics of KET01 in TRD. Methods KET01-02 was a randomized, double-blind phase 2 trial in outpatients with TRD comparing adjunct 120 mg (n=42) or 240 mg (n=40) oral KET01 once-daily for 3 weeks to placebo (PBO, n=40). The primary endpoint was change from baseline in the MADRS mean score on Day 21. KET01-03 was a randomized, double-blind, cross-over phase I trial in 26 healthy volunteers comparing single doses of 240 mg oral KET01 and 84 mg an approved intranasal formulation of eketamine. The primary endpoint was maximum change of Clinician-Administered Dissociative States Scale (CADSS) score from baseline. Results KET01-03 trial; the mean (±SD) maximum change of CADSS score within 24 hours after dosing was 29.6±12.5 for intranasal eketamine and 0.7±1.7 for KET01 (p4 and increase from baseline. At 7 hours post first KET01 dose (240 mg), plasma concentration of ketamine (38.7±27.0 ng/ml) was lower than its metabolites norketamine (267.5±81.6 ng/ml) and hydroxynorketamine (190.2±85.5 ng/ml). 240 mg/day KET01 induced clinically relevant reduction from baseline in MADRS score already within the first 7 hours of treatment (-7.65; Δ vs PBO: -2.22, n.s.), with a statistically significant separation on Day 4 (-10.02; Δ vs PBO: -3.66, p=0.020) and Day 7 (-12.21; Δ vs PBO: -3.95, p=0.042). MADRS score decrease was sustained throughout Day 21 (-13.15; Δ vs PBO: -1.82, n.s.), and during 4-week follow-up (-12.51; Δ vs PBO: -3.35, n.s.). Treatment-emergent adverse events occurred in 47.5%, 50.0%, and 62.5% of patients in the PBO, 120 mg/day, and 240 mg/day KET01 group, respectively. Conclusions Oral 240 mg/day KET01 induces a rapid, and clinically relevant reduction of depressive symptoms with only minimal signs of dissociation, potentially due to lower ketamine levels and increased norketamine and hydroxynorketamine levels compared to intravenous administration. Our results suggest that KET01 may be an efficacious and safe take-at-home adjunct treatment for TRD. Disclosure of Interest C. zu Eulenburg Employee of: HMNC Brain Health, E. Papanastasiou Employee of: HMNC Brain Health, K. Schmid Employee of: Develco Pharma, A. Damyanova Employee of: HMNC Brain Health, A. Glas Employee of: HMNC Brain Health, C. Strote Employee of: HMNC Brain Health, L. Arvastson Employee of: HMNC Brain Health, H. Eriksson Employee of: HMNC Brain Health

Using the reaction–diffusion model for hydrogen (H) trapping in spherical cavities in metals (Zibrov and Schmid, 2022), we theoretically analyze the case of H trapping only in chemisorption sites at the cavity surface. We show that the model can be reduced to a form that is similar to the conventional model of H trapping in point defects. The reduced model includes analytical expressions for correction factors to account for correlated H retrapping by the same cavity and inhomogeneous H potential energy landscape in the vicinity of the cavity surface. We show that these correction factors play a significant role in thermal desorption (TDS) simulations only in the case of very low cavity number densities (detrapping-limited regime), which is rarely encountered in experiments.

For future fusion power plants, the reduced activation ferritic/martensitic (RAFM) steel EUROFER is considered to be the primary choice as a structural material for plasma facing components (PFC) of the first wall, such as the blanket modules. Its exposure to high energy fusion neutrons will lead to creation of radiation-induced defects, which could act as trapping sites for hydrogen isotopes (HI) and consequently, strongly affect HI diffusion and retention. For predictive simulations of HI retention, the concentration of these trap sites needs to be known as a function of the temperature. In this work, EUROFER samples are irradiated by 20 MeV W-ions at 290 K to create displacement damage. Subsequently, they are exposed to deuterium (D) plasma at 370 K to decorate the created defects. Partial thermal desorption spectroscopy (TDS) is conducted in 50 K steps up to 620 K. D depth profiles are determined by nuclear reaction analysis (NRA) after each partial-TDS step. Following this analysis, the defects are again decorated with D and the D depth profiles are measured again by NRA to monitor the evolution of the concentration of trap sites. Most of the D is lost already at 470 K due to thermal de-trapping. Full recovery of the displacement damage is reached at 620 K.

B cell antigen receptor (BCR) signaling is a key driver of growth and survival in both normal and malignant B cells. Several lines of evidence support an important pathogenic role of the BCR in chronic lymphocytic leukemia (CLL). The significant improvement of CLL patients’ survival with the use of various BCR pathway targeting inhibitors, supports a crucial involvement of BCR signaling in the pathogenesis of CLL. Although the treatment landscape of CLL has significantly evolved in recent years, no agent has clearly demonstrated efficacy in patients with treatment-refractory CLL in the long run. To identify new drug targets and mechanisms of drug action in neoplastic B cells, a detailed understanding of the molecular mechanisms of leukemic transformation as well as CLL cell survival is required. In the last decades, studies of genetically modified CLL mouse models in line with CLL patient studies provided a variety of exciting data about BCR and BCR-associated kinases in their role in CLL pathogenesis as well as disease progression. BCR surface expression was identified as a particularly important factor regulating CLL cell survival. Also, BCR-associated kinases were shown to provide a crosstalk of the CLL cells with their tumor microenvironment, which highlights the significance of the cells’ milieu in the assessment of disease progression and treatment. In this review, we summarize the major findings of recent CLL mouse as well as patient studies in regard to the BCR signalosome and discuss its relevance in the clinics.

Timely regulation of carbon metabolic pathways is essential for cellular processes and to prevent futile cycling of intracellular metabolites. In Halobacterium salinarum, a hypersaline adapted archaeon, a sugar-sensing TrmB family protein controls gluconeogenesis and other biosynthetic pathways. Notably, Hbt. salinarum does not utilize carbohydrates for energy, uncommon among Haloarchaea. We characterized a TrmB-family transcriptional regulator in a saccharolytic generalist, Haloarcula hispanica, to investigate whether the targets and function of TrmB, or its regulon, is conserved in related species with distinct metabolic capabilities. In Har. hispanica, TrmB binds to 15 sites in the genome and induces the expression of genes primarily involved in gluconeogenesis and tryptophan biosynthesis. An important regulatory control point in Hbt. salinarum, activation of ppsA and repression of pykA, is absent in Har. hispanica. Contrary to its role in Hbt. salinarum and saccharolytic hyperthermophiles, TrmB does not act as a global regulator: it does not directly repress the expression of glycolytic enzymes, peripheral pathways such as cofactor biosynthesis, or catabolism of other carbon sources in Har. hispanica. Cumulatively, these findings suggest rewiring of the TrmB regulon alongside metabolic network evolution in Haloarchaea.

The reduced activation ferritic martensitic steel EUROFER is one of the foreseen structural materials for future fusion reactors. The exposure to energetic fusion neutrons will generate displacement damage in the steel which can act as trapping sites for hydrogen isotopes (HIs). For predictive simulations of HI retention the concentration of the trap sites and HI trap binding energies are needed. In this work the input parameters for rate equation modeling of HI transport in displacement-damaged EUROFER are determined by fitting recently obtained thermal desorption spectroscopy (TDS) data. During these simultaneous fits of all TDS data the input parameters were constrained as much as possible by using literature data and measured HI concentration depth profiles. A comparison of gas phase loading at low pressures with literature data on solubility suggested the presence of a surface limit for D uptake from the gas phase. However, while modeling plasma loading with energetic particles this surface limit results in an overestimation of the D uptake. The only way to reconcile the lack of D loading from the gas-phase at low pressures and match the measured uptake of D during plasma loading, was to introduce a removal process for chemisorbed D from the surface by the energetic particle impact from the plasma. With this surface model and the fitted trapping parameters it is possible to simulate the measured TDS data and the observed lack of gas loading at low pressures. The so configured rate equation model can now be used for prediction of D transport and retention in EUROFER.

Experiments on ASDEX Upgrade (AUG) in 2021 and 2022 have addressed a number of critical issues for ITER and EU DEMO. A major objective of the AUG programme is to shed light on the underlying physics of confinement, stability, and plasma exhaust in order to allow reliable extrapolation of results obtained on present day machines to these reactor-grade devices. Concerning pedestal physics, the mitigation of edge localised modes (ELMs) using resonant magnetic perturbations (RMPs) was found to be consistent with a reduction of the linear peeling-ballooning stability threshold due to the helical deformation of the plasma. Conversely, ELM suppression by RMPs is ascribed to an increased pedestal transport that keeps the plasma away from this boundary. Candidates for this increased transport are locally enhanced turbulence and a locked magnetic island in the pedestal. The enhanced D-alpha (EDA) and quasi-continuous exhaust (QCE) regimes have been established as promising ELM-free scenarios. Here, the pressure gradient at the foot of the H-mode pedestal is reduced by a quasi-coherent mode, consistent with violation of the high-n ballooning mode stability limit there. This is suggestive that the EDA and QCE regimes have a common underlying physics origin. In the area of transport physics, full radius models for both L- and H-modes have been developed. These models predict energy confinement in AUG better than the commonly used global scaling laws, representing a large step towards the goal of predictive capability. A new momentum transport analysis framework has been developed that provides access to the intrinsic torque in the plasma core. In the field of exhaust, the X-Point Radiator (XPR), a cold and dense plasma region on closed flux surfaces close to the X-point, was described by an analytical model that provides an understanding of its formation as well as its stability, i.e., the conditions under which it transitions into a deleterious MARFE with the potential to result in a disruptive termination. With the XPR close to the divertor target, a new detached divertor concept, the compact radiative divertor, was developed. Here, the exhaust power is radiated before reaching the target, allowing close proximity of the X-point to the target. No limitations by the shallow field line angle due to the large flux expansion were observed, and sufficient compression of neutral density was demonstrated. With respect to the pumping of non-recycling impurities, the divertor enrichment was found to mainly depend on the ionisation energy of the impurity under consideration. In the area of MHD physics, analysis of the hot plasma core motion in sawtooth crashes showed good agreement with nonlinear 2-fluid simulations. This indicates that the fast reconnection observed in these events is adequately described including the pressure gradient and the electron inertia in the parallel Ohm’s law. Concerning disruption physics, a shattered pellet injection system was installed in collaboration with the ITER International Organisation. Thanks to the ability to vary the shard size distribution independently of the injection velocity, as well as its impurity admixture, it was possible to tailor the current quench rate, which is an important requirement for future large devices such as ITER. Progress was also made modelling the force reduction of VDEs induced by massive gas injection on AUG. The H-mode density limit was characterised in terms of safe operational space with a newly developed active feedback control method that allowed the stability boundary to be probed several times within a single discharge without inducing a disruptive termination. Regarding integrated operation scenarios, the role of density peaking in the confinement of the ITER baseline scenario (high plasma current) was clarified. The usual energy confinement scaling ITER98( p,y ) does not capture this effect, but the more recent H20 scaling does, highlighting again the importance of developing adequate physics based models. Advanced tokamak scenarios, aiming at large non-inductive current fraction due to non-standard profiles of the safety factor in combination with high normalised plasma pressure were studied with a focus on their access conditions. A method to guide the approach of the targeted safety factor profiles was developed, and the conditions for achieving good confinement were clarified. Based on this, two types of advanced scenarios (‘hybrid’ and ‘elevated’ q -profile) were established on AUG and characterised concerning their plasma performance.

After a long device enhancement phase, scientific operation resumed in 2022. The main new device components are the water cooling of all plasma facing components and the new water-cooled high heat flux divertor units. Water cooling allowed for the first long-pulse operation campaign. A maximum discharge length of 8 min was achieved with a total heating energy of 1.3 GJ. Safe divertor operation was demonstrated in attached and detached mode. Stable detachment is readily achieved in some magnetic configurations but requires impurity seeding in configurations with small magnetic pitch angle within the edge islands. Progress was made in the characterization of transport mechanisms across edge magnetic islands: Measurement of the potential distribution and flow pattern reveals that the islands are associated with a strong poloidal drift, which leads to rapid convection of energy and particles from the last closed flux surface into the scrape-off layer. Using the upgraded plasma heating systems, advanced heating scenarios were developed, which provide improved energy confinement comparable to the scenario, in which the record triple product for stellarators was achieved in the previous operation campaign. However, a magnetic configuration-dependent critical heating power limit of the electron cyclotron resonance heating was observed. Exceeding the respective power limit leads to a degradation of the confinement.

In 2021 JET exploited its unique capabilities to operate with T and D–T fuel with an ITER-like Be/W wall (JET-ILW). This second major JET D–T campaign (DTE2), after DTE1 in 1997, represented the culmination of a series of JET enhancements—new fusion diagnostics, new T injection capabilities, refurbishment of the T plant, increased auxiliary heating, in-vessel calibration of 14 MeV neutron yield monitors—as well as significant advances in plasma theory and modelling in the fusion community. DTE2 was complemented by a sequence of isotope physics campaigns encompassing operation in pure tritium at high T-NBI power. Carefully conducted for safe operation with tritium, the new T and D–T experiments used 1 kg of T (vs 100 g in DTE1), yielding the most fusion reactor relevant D–T plasmas to date and expanding our understanding of isotopes and D–T mixture physics. Furthermore, since the JET T and DTE2 campaigns occurred almost 25 years after the last major D–T tokamak experiment, it was also a strategic goal of the European fusion programme to refresh operational experience of a nuclear tokamak to prepare staff for ITER operation. The key physics results of the JET T and DTE2 experiments, carried out within the EUROfusion JET1 work package, are reported in this paper. Progress in the technological exploitation of JET D–T operations, development and validation of nuclear codes, neutronic tools and techniques for ITER operations carried out by EUROfusion (started within the Horizon 2020 Framework Programme and continuing under the Horizon Europe FP) are reported in (Litaudon et al Nucl. Fusion accepted), while JET experience on T and D–T operations is presented in (King et al Nucl. Fusion submitted).

Future fusion reactors will have to breed enough tritium (T) to sustain continuous operation and to produce excess T to power up other fusion reactors. Therefore, T is a scarce resource that must not be lost inside the fusion power plants systems. The factor that describes the T production is the ‘tritium breeding ratio’ (TBR) which is the ratio of the breading rate in atoms per second to the burn rate in atoms per second. Its value is calculated from neutronics analyses of the breeding process in the blanket and coupled dynamics of the T processing plant. However, these calculations generally ignore the T transport and loss in the first wall by assuming essentially instantaneous recycling of the impinging T in-flux. In this paper the transport and retention of T in the main chamber first wall of a future EU-DEMO reactor is investigated based on the available material data and expected particle loads onto the wall. Two breeding blanket concepts are compared WCLL (water cooled lithium lead) and HCPB (helium cooled pebble bed) and the resulting wall-loss probabilities are compared with a simple balance model that describes the maximum allowable wall loss given a TBR to achieve T-self-sufficiency.

The paper provides an overview of recent modelling of global material erosion and deposition in the fusion devices Wendelstein 7-X (W7-X), JET and ITER using the Monte-Carlo code ERO2.0. For validating the modelling tool in a three-dimensional environment, W7-X simulations are performed to describe carbon erosion from the graphite test divertor units, which were equipped in operational phase OP 1.2 and analysed post-mortem. Synthetic spectroscopy of carbon line emission is compared with experimental results from the divertor spectrometer measurement system, showing a good agreement in the e-folding lengths in the radial intensity profiles of carbon. In the case of metallic wall materials, earlier modelling of the Be/W environment in JET and ITER is revisited and extended with an updated set of sputtering and reflection data, as well as including the mixing model for describing the Be/W dynamics in the divertor. Motivated by recent H/D/T isotope experiments in JET, limited and diverted configuration pulses are modelled, showing the expected trend of both Be and W erosion increasing with isotope mass. For the JET diverted configuration pulses, it is shown that Be migrates predominantly to the upper part of the inner divertor where it initially leads to strong W erosion. With longer exposure time, the growth of a Be deposited layer leads to a reduction of W erosion in that region. A similar trend is observed in simulations of the ITER baseline Q = 10 scenario, however with a more symmetric Be migration pattern leading to deposition also on the outer divertor.

An integral approach to plasma-wall interaction (PWI) modelling for DEMO is presented, which is part of the EUROfusion Theory and Advanced Simulation Coordination activities that were established to advance the understanding and predictive capabilities for the modelling of existing and future fusion devices using a modern advanced computing approach. In view of the DEMO design, the aim of PWI modelling activities is to assess safety-relevant information regarding the erosion of plasma-facing components (PFCs), including its impact on plasma contamination, dust production, fuel inventory, and material response to transient events. This is achieved using a set of powerful and validated computer codes that deal with particular PWI aspects and interact with each other by means of relevant data exchange. Steady state erosion of tungsten PFC and subsequent transport and re-deposition of eroded material are simulated with the ERO2.0 code using a DEMO plasma background produced by dedicated SOLPS-ITER simulations. Dust transport simulations in steady state plasma also rely on the respective SOLPS-ITER solutions and are performed with the MIGRAINe code. In order to improve simulations of tungsten erosion in the divertor of DEMO, relevant high density sheath models are being developed based on particle-in-cell (PIC) simulations with the state-of-the-art BIT code family. PIC codes of the SPICE code family, in turn, provide relevant information on multi-emissive sheath physics, such as semi-empirical scaling laws for field-assisted thermionic emission. These scaling laws are essential for simulations of material melting under transient heat loads that are performed with the recently developed MEMENTO code, the successor of MEMOS-U. Fuel retention simulations assess tritium retention in tungsten and structural materials, as well as fuel permeation to the coolant, accounting for neutron damage. Simulations for divertor monoblocks of different sizes are performed using the FESTIM code, while for the first wall the TESSIM code is applied. Respective code-code dependencies and interactions, as well as modelling results achieved to date are discussed in this contribution.

ABSTRACT Histone proteins are found across diverse lineages of Archaea, many of which package DNA and form chromatin. However, previous research has led to the hypothesis that the histone-like proteins of high-salt-adapted archaea, or halophiles, function differently. The sole histone protein encoded by the model halophilic species Halobacterium salinarum, HpyA, is nonessential and expressed at levels too low to enable genome-wide DNA packaging. Instead, HpyA mediates the transcriptional response to salt stress. Here we compare the features of genome-wide binding of HpyA to those of HstA, the sole histone of another model halophile, Haloferax volcanii. hstA, like hpyA, is a nonessential gene. To better understand HpyA and HstA functions, protein-DNA binding data (chromatin immunoprecipitation sequencing [ChIP-seq]) of these halophilic histones are compared to publicly available ChIP-seq data from DNA binding proteins across all domains of life, including transcription factors (TFs), nucleoid-associated proteins (NAPs), and histones. These analyses demonstrate that HpyA and HstA bind the genome infrequently in discrete regions, which is similar to TFs but unlike NAPs, which bind a much larger genomic fraction. However, unlike TFs that typically bind in intergenic regions, HpyA and HstA binding sites are located in both coding and intergenic regions. The genome-wide dinucleotide periodicity known to facilitate histone binding was undetectable in the genomes of both species. Instead, TF-like and histone-like binding sequence preferences were detected for HstA and HpyA, respectively. Taken together, these data suggest that halophilic archaeal histones are unlikely to facilitate genome-wide chromatin formation and that their function defies categorization as a TF, NAP, or histone. IMPORTANCE Most cells in eukaryotic species—from yeast to humans—possess histone proteins that pack and unpack DNA in response to environmental cues. These essential proteins regulate genes necessary for important cellular processes, including development and stress protection. Although the histone fold domain originated in the domain of life Archaea, the function of archaeal histone-like proteins is not well understood relative to those of eukaryotes. We recently discovered that, unlike histones of eukaryotes, histones in hypersaline-adapted archaeal species do not package DNA and can act as transcription factors (TFs) to regulate stress response gene expression. However, the function of histones across species of hypersaline-adapted archaea still remains unclear. Here, we compare hypersaline histone function to a variety of DNA binding proteins across the tree of life, revealing histone-like behavior in some respects and specific transcriptional regulatory function in others.

The reduced activation ferritic martensitic steel EUROFER is one of the foreseen structural materials for future fusion reactors. The exposure to energetic fusion neutrons will generate displacement damage in the steel which acts as trapping sites for hydrogen isotopes (HIs). For predictive simulations of HI retention the concentration of the trap sites and HI trap-binding energies are needed. In this work the potential influence of HIs present during displacement damage on the resulting trap site concentration is investigated. EUROFER samples are exposed to multiple sequences of displacement damage by MeV W-ions and subsequent loading by D-ions from a low temperature plasma. After each of these damage/loading sequences the D depth profile in the surfaces is measured by nuclear reaction analysis (NRA) using a 3He beam. These depth profiles show a clear increase in the trap site concentration when the displacement damaging step is performed on a sample already containing trapped D. The presence of 3He in analysis spots from previous NRA-depth profiling also results in a strong increase of local retention due to traps formed by the implanted 3He. Thermal desorption spectra show that in EUROFER retention is dominated by the bulk, even in the presence of displacement damage in the near surface. These results suggest that the presence of D and He in EUROFER will result in increased retention compared to pure EUROFER under displacement damage.

To use skyrmions to store information, an effective method for writing and deleting them is required. Here, Chen et al demonstrate the writing and deleting of skyrmions at room temperature by using hydrogen adsorption to change the magnetic anisotropy of the metallic multilayer hosting the skyrmions.

The retention by co-deposition of fuel species in Be-layers, forming due to migration of Be eroded from the 3D-shaped main chamber wall in ITER, was modeled with WallDYN-3D. The goal was to investigate the influence of the 3D shaping on Be layer formation location, compared to previous 2D calculations for a perfectly toroidally symmetric main chamber Be wall. The calculation showed that the shaping results in a large number of partially plasma shadowed regions in the main chamber, where Be can deposit and form layers. Depending on the main chamber plasma solution, this results in a shift of the primary Be layer deposition location from the divertor in 2D to the main chamber in 3D calculations. The deposition location is important because the higher average hydrogen isotope (HI) particle energy in the main chamber affects HI content in the co-deposited layers. However, for the currently available HI/Be scaling laws the resulting increase in HI/Be is small. A comparison of the 3D-shaped Be-main chamber erosion calculated recently by ERO2.0 and by WallDYN-3D in this work, shows very similar erosion patterns. However, differences exist in the deposition locations because, in contrast to ERO2.0, WallDYN-3D takes re-erosion of deposited Be into account. To match the absolute amount of Be erosion the Be-sputter yields used by WallDYN-3D have to be increased by a factor of 1.5, due to a different erosion yield database used by ERO2.0 which results in higher yields at oblique impact angles. This uncertainty in the sputter yield, but also in the HI/Be scaling laws, make an uncertainty quantification necessary. Applying polynomial chaos expansion to the Be layer growth rate and HI-retention rate by co-deposition, yields an uncertainty of ≈100% in both quantities, due to the uncertainties in the sputter yields and the fit parameters of the HI/Be scaling laws.

Tritium self-sufficiency is a key requirement for future fusion power plants. Therefore, it will be necessary to minimize tritium losses to the surrounding systems, such as the tritium breeding modules, plasma-facing components, cooling system, etc. These components and systems will act also as a tritium sink, as tritium will be retained in the metal walls in traps produced during manufacturing or induced by neutron irradiation. The design of the tritium breeding systems and plasma-facing components will therefore have a direct impact on the performance, operational safety and cost of any future power plant. Consequently, accurate modeling of tritium transport and retention in these systems is needed for future engineering designs of the tritium breeding systems and supporting safety requirements. In this work, tritium permeation and retention was modeled with the diffusion-transport code TESSIM-X for the current European WCLL (Water Cooled Lithium Lead) Test Blanket Module (TBM) for the ITER TBM Programme, with the inclusion of neutron-induced traps. Trap saturation is considered for dpa values of 0.25 and above, leading to an increase in trap concentrations relative to undamaged material of roughly a factor 3. The code was also benchmarked against the well-established TMAP7 code.

We present a reaction–diffusion model of hydrogen (H) trapping and release from a metal containing an array of cavities. The model is based on a kinetic description of H trapping in chemisorption sites at the cavity surface and H2 gas precipitation in the cavity volume. Significant differences compared to the case of a single cavity (Zibrov and Schmid, 2022) are observed at high cavity number densities due to retrapping effects. They affect the shape of thermal desorption spectroscopy (TDS) curves, the variation of the TDS peak position with the heating rate, and the desorption at a fixed temperature. The TDS spectra from cavities exhibit features that are very difficult to describe with conventional models but are readily observed in experiments: Sharp rising edges of desorption peaks and constant desorption at a fixed temperature. Also the dynamics of H transport and trapping in the material containing cavities differs from that for point defects, especially at low temperatures. The non-equilibrium effects in the interaction of H with cavities are particularly important for metals with low H solubility, such as tungsten and beryllium.

Most of the terrestrial legged locomotion gaits, like human walking, necessitate energy dissipation upon ground collision. In humans, the heel mostly performs net-negative work during collisions, and it is currently unclear how it dissipates that energy. Based on the laws of thermodynamics, one possibility is that the net-negative collision work may be dissipated as heat. If supported, such a finding would inform the thermoregulation capacity of human feet, which may have implications for understanding foot complications and tissue damage. Here, we examined the correlation between energy dissipation and thermal responses by experimentally increasing the heel’s collisional forces. Twenty healthy young adults walked overground on force plates and for 10 min on a treadmill (both at 1.25 ms−1) while wearing a vest with three different levels of added mass (+0%, +15%, & +30% of their body mass). We estimated the heel’s work using a unified deformable segment analysis during overground walking. We measured the heel’s temperature immediately before and after each treadmill trial. We hypothesized that the heel’s temperature and net-negative work would increase when walking with added mass, and the temperature change is correlated with the increased net-negative work. We found that walking with +30% added mass significantly increased the heel’s temperature change by 0.72 ± 1.91 ℃ (p = 0.009) and the magnitude of net-negative work (extrapolated to 10 min of walking) by 326.94 ± 379.92 J (p = 0.005). However, we found no correlation between the heel’s net-negative work and temperature changes (p = 0.277). While this result refuted our second hypothesis, our findings likely demonstrate the heel’s dynamic thermoregulatory capacity. If all the negative work were dissipated as heat, we would expect excessive skin temperature elevation during prolonged walking, which may cause skin complications. Therefore, our results likely indicate that various heat dissipation mechanisms control the heel’s thermodynamic responses, which may protect the health and integrity of the surrounding tissue. Also, our results indicate that additional mechanical factors, besides energy dissipation, explain the heel’s temperature rise. Therefore, future experiments may explore alternative factors affecting thermodynamic responses, including mechanical (e.g., sound & shear-stress) and physiological mechanisms (e.g., sweating, local metabolic rate, & blood flow).

Replication and reproducibility are an important component of scientific research. One reason research is not replicable is the misuse of statistical techniques. Educators can teach the importance of research replication by having students perform a replication study as part of a graduate assistantship or their coursework. In this article, we describe the components of a replication study, the process of conducting a replication study, and how to use the replication process as a teaching tool. Two biostatistics PhD students performed four full replication studies as part of their Graduate Assistantship and another 22 students performed a partial replication as their final project for a biostatistics service course. Students were queried for their feedback about their learning during the replication process. The PhD students indicated gaining a clear understanding of the importance of communicating statistical methods in publications, experience in communicating statistical techniques in writing, coding in various platforms, multiple statistical techniques that could be applied as robustness checks, and the importance of documentation. The students from the service course indicated gaining confidence in their analysis skills and a majority of the students indicated finding all aspects of the replication process enjoyable with the exception of writing the final report.

We present simulations of deuterium thermal desorption spectra (TDS) from a single nm-sized spherical cavity in tungsten. We study both D2gas-filled cavities and cavities with trapping only at surface sites. The simulations are based on the diffusion theory and the kinetic model of deuterium interaction with metal surfaces. We show that the previously used approaches based on local thermodynamic equilibrium between D2gas and the subsurface solute deuterium are inadequate for simulating TDS spectra. We demonstrate the influence of cavity radius, D2gas pressure, the parameters of the surface and the bulk. The deuterium release rate from a gas-filled cavity at a fixed temperature (below the TDS peak) stays constant until the D2gas is depleted, in contrast to exponential decay observed for conventional deuterium trapping sites. Using the simulations and a simplified analytic model we demonstrate that for cavities the dependence of the TDS peak position on the heating rate does not follow exactly the Kissinger equation.

Abstract Background There is scientific evidence that older adults aged 65 and over walk with increased step width variability which has been associated with risk of falling. However, there are presently no threshold levels that define the optimal reference range of step width variability. Thus, the purpose of our study was to estimate the optimal reference range for identifying older adults with normative and excessive step width variability. Methods We searched systematically the BMC, Cochrane Library, EBSCO, Frontiers, IEEE, PubMed, Scopus, SpringerLink, Web of Science, Wiley, and PROQUEST databases until September 2018, and included the studies that measured step width variability in both younger and older adults during walking at self-selected speed. Data were pooled in meta-analysis, and standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated. A single-decision threshold method based on the Youden index, and a two-decision threshold method based on the uncertain interval method were used to identify the optimal threshold levels (PROSPERO registration: CRD42018107079). Results Ten studies were retrieved (older adults = 304; younger adults = 219). Step width variability was higher in older than in younger adults (SMD = 1.15, 95% CI = 0.60; 1.70; t = 4.72, p = 0.001). The single-decision method set the threshold level for excessive step width variability at 2.14 cm. For the two-decision method, step width variability values above the upper threshold level of 2.50 cm were considered excessive, while step width variability values below the lower threshold level of 1.97 cm were considered within the optimal reference range. Conclusion Step width variability is higher in older adults than in younger adults, with step width variability values above the upper threshold level of 2.50 cm to be considered as excessive. This information could potentially impact rehabilitation technology design for devices targeting lateral stability during walking.

An efficient removal of He ash by active pumping in future fusion devices is necessary to avoid fuel dilution and not degrade the core confinement properties. Therefore, a deep understanding of the underlying physics mechanisms is mandatory. Helium exhaust has been experimentally investigated at the ASDEX Upgrade tokamak. This is an ideal test environment, thanks to the ITER-like divertor geometry, an extensive diagnostics coverage and the presence of plasma-facing components made of tungsten. The exhaust efficiency, characterized by the He compression in the divertor, was found to improve with increasing divertor neutral pressure but to degrade with detachment. A multi-reservoir particle balance model was developed to interpret the observed exhaust dynamics, accounting for plasma transport and wall retention. The limited performance of the pumping system and the efficient helium retention capability of the tungsten wall were identified to have the strongest impact on the exhaust dynamics.

Tritium self-sufficiency presents a critical engineering challenge for DEMO, requiring efficient breeding and extraction systems, as well as minimizing tritium losses to the surrounding systems, such as plasma-facing components, vacuum vessel, cooling system, etc. Structural and plasma-facing components will act as a tritium sink, as tritium will be accumulated in the bulk of these components due to energetic particle bombardment and may permeate out of the vacuum system. The design of the plasma-facing components will consequently directly influence the plant lifetime, operational safety and cost of any future power plant. Therefore, modeling of tritium retention and permeation in these components is required for the engineering designs of the tritium breeding and safety systems. In this work, the diffusion-transport code TESSIM-X is benchmarked against the well-established TMAP7 code and a comparison with a simplified DEMO-relevant test case is performed. The use of either code for modeling of DEMO conditions is discussed. Following this, TESSIM-X is used to provide a preliminary assessment of tritium permeation and retention in the DEMO first wall, based on the current WCLL (Water Cooled Lithium Lead) and HCPB (Helium Cooled Pebble Bed) breeding blanket designs.

Boronization is commonly utilized in tokamaks to suppress intrinsic impurities, most notably oxygen from residual water vapor. However, this is a temporary solution, as oxygen levels typically return to pre-boronization levels following repeated plasma exposure. The global impurity migration model WallDYN has been applied to the post-boronization surface impurity evolution in NSTX-U. A “Thin Film Model” has been incorporated into WallDYN to handle spatially inhomogeneous conditioning films of varying thicknesses, together with an empirical boron conditioning model for the NSTX-U glow discharge boronization process. The model qualitatively reproduces the spatial distribution of boron in the NSTX-U vessel, the spatially-resolved divertor emission pattern, and the increase in oxygen levels following boronization. The simulations suggest that oxygen is primarily sourced from wall locations without heavy plasma flux or significant boron deposition, namely the lower and upper passive plates and the lower private flux zone.

Tritium self-sufficiency is a critical issue for the production of nuclear fusion energy. Here we quantify the impact of co-deposition of eroded wall material and fuel on the tritium particle balance in a hypothetical reactor system. The expected ITER plasma parameters and geometry are used to estimate the amount of eroded material from a full tungsten, beryllium or carbon device. Measured D concentrations in co-deposits are extrapolated to the wall temperature expected in future reactors and used along with these eroded flux estimates to determine the net loss probability of tritium from the device due to co-deposition. The use of liquid divertor surfaces is also considered with the amount of tritium residing in the recirculating liquid estimated. The general conclusion, from a tritium self-sufficiency viewpoint, is that one should avoid low-Z materials that readily form hydrogen bonds, in favor of high-Z non-hydride forming materials. Keywords: Plasma-material interactions, Co-deposition, Tritium, Self-sufficiency

The global impurity migration code WallDYN was coupled to the 3D scrape off layer plasma solver EMC3-Eirene in order to make WallDYN applicable to 3D, non-toroidally symmetric, geometries. To make EMC3-Eirene suitable for migration studies its impurity transport module was extended to not just compute the impurity density in the plasma but also their deposition on the wall tiles. Originally EMC3 treats the impurity transport in the plasma as a diffusion convection problem thereby assuming immediate equilibration with the local background plasma in order to derive the local parallel convection velocity. While this is a reasonable approximation for light elements, it is not suitable for the treatment of heavy element which need significant time to equilibrate their velocity and temperature with the background plasma. Therefore EMC3-Eirene was augmented by a new kinetic impurity transport module that handles acceleration and thermalisation in a manner similar to what is implemented in the 2D trace impurity transport code DIVIMP. This paper will first describe the modification introduced in EMC3-Eirene and then show the differences between the impurity transport models and the new possibilities now available in WallDYN to interpret migration studies in non-toroidally symmetric geometries . PACS: 61.80.Jh, 52.25.Vy, 52.65, 52.40.Hf, EMC3, Erosion & deposition, Sputtering, Edge modeling

During the interaction of the scrape off layer (SOL) plasma with the first wall the evolution of both wall and plasma are tightly coupled: The erosion of the first wall leads to an impurity concentration in the plasma which affects the particle and power balance in the plasma. In turn the impurities, when leaving the plasma via transport, can form deposits and mixed materials, far away from their initial source location. These deposits can be eroded, allowing the impurities to stepwise migrate through the fusion device until they end up at a location where the plasma at the wall is cold enough and no further erosion occurs. To describe these processes an integrated model of surface evolution and plasma transport of impurities is needed. The WallDYN code achieves this required coupling of processes by parameterising the output of surface evolution- and plasma impurity-migration-codes by analytical models. For a given fixed background plasma it evolves the surface composition, derives impurity flux into and from the plasma and can from this derive the impurity densities in the plasma. This paper will show the importance of including this recycling of impurities at the wall in impurity migration modelling: The 13CH4seeding experiment performed in the Wendelstein 7-X Stellerator is modelled using the recent extension of the WallDYN code to 3D plasma and wall geometries. A comparison with post mortem analysis of the 13C deposition shows both qualitative and quantitative agreement with the WallDYN calculations.

Despite intense recent research interest in archaea, the scientific community has experienced a bottleneck in the study of genome-scale gene expression experiments by RNA-seq due to the lack of commercial and specifically designed rRNA depletion kits. The high rRNA:mRNA ratio (80–90%: ~10%) in prokaryotes hampers global transcriptomic analysis. Insufficient ribodepletion results in low sequence coverage of mRNA, and therefore, requires a substantially higher number of replicate samples and/or sequencing reads to achieve statistically reliable conclusions regarding the significance of differential gene expression between case and control samples. Here, we show that after the discontinuation of the previous version of RiboZero (Illumina, San Diego, CA, USA) that was useful in partially or completely depleting rRNA from archaea, archaeal transcriptomics studies have experienced a slowdown. To overcome this limitation, here, we analyze the efficiency for four different hybridization-based kits from three different commercial suppliers, each with two sets of sequence-specific probes to remove rRNA from four different species of halophilic archaea. We conclude that the key for transcriptomic success with the currently available tools is the probe-specificity for the rRNA sequence hybridization. With this paper, we provide insights into the archaeal community for selecting certain reagents and strategies over others depending on the archaeal species of interest. These methods yield improved RNA-seq sensitivity and enhanced detection of low abundance transcripts.

Substantive changes in gene expression, metabolism, and the proteome are manifested in overall changes in microbial population growth. Quantifying how microbes grow is therefore fundamental to areas such as genetics, bioengineering, and food safety. Traditional parametric growth curve models capture the population growth behavior through a set of summarizing parameters. However, estimation of these parameters from data is confounded by random effects such as experimental variability, batch effects or differences in experimental material. A systematic statistical method to identify and correct for such confounding effects in population growth data is not currently available. Further, our previous work has demonstrated that parametric models are insufficient to explain and predict microbial response under non-standard growth conditions. Here we develop a hierarchical Bayesian non-parametric model of population growth that identifies the latent growth behavior and response to perturbation, while simultaneously correcting for random effects in the data. This model enables more accurate estimates of the biological effect of interest, while better accounting for the uncertainty due to technical variation. Additionally, modeling hierarchical variation provides estimates of the relative impact of various confounding effects on measured population growth.

ABSTRACT Precise control of the cell cycle is central to the physiology of all cells. In prior work we demonstrated that archaeal cells maintain a constant size; however, the regulatory mechanisms underlying the cell cycle remain unexplored in this domain of life. Here, we use genetics, functional genomics, and quantitative imaging to identify and characterize the novel CdrSL gene regulatory network in a model species of archaea. We demonstrate the central role of these ribbon-helix-helix family transcription factors in the regulation of cell division through specific transcriptional control of the gene encoding FtsZ2, a putative tubulin homolog. Using time-lapse fluorescence microscopy in live cells cultivated in microfluidics devices, we further demonstrate that FtsZ2 is required for cell division but not elongation. The cdrS-ftsZ2 locus is highly conserved throughout the archaeal domain, and the central function of CdrS in regulating cell division is conserved across hypersaline adapted archaea. We propose that the CdrSL-FtsZ2 transcriptional network coordinates cell division timing with cell growth in archaea. IMPORTANCE Healthy cell growth and division are critical for individual organism survival and species long-term viability. However, it remains unknown how cells of the domain Archaea maintain a healthy cell cycle. Understanding the archaeal cell cycle is of paramount evolutionary importance given that an archaeal cell was the host of the endosymbiotic event that gave rise to eukaryotes. Here, we identify and characterize novel molecular players needed for regulating cell division in archaea. These molecules dictate the timing of cell septation but are dispensable for growth between divisions. Timing is accomplished through transcriptional control of the cell division ring. Our results shed light on mechanisms underlying the archaeal cell cycle, which has thus far remained elusive.

The electron reflectivity from NiO thin films grown on Ag(001) has been systematically studied as a function of film thickness and electron energy. A strong electron quantum interference effect was observed from the NiO film, which is used to derive the unoccupied band dispersion above the Fermi surface along the Γ−X direction using the phase accumulation model. The experimental bands agree well with first-principles calculations. A weaker electron quantum interference effect was also observed from the CoO film.

Increasing people's willingness to donate organs after their death requires effective communication strategies. In two preregistered studies, we assessed whether humorous entertainment education formats on organ donation elicit positive effects on knowledge, fears, attitudes, and behavioral intentions-both immediately after the treatment and four weeks later. We test whether perceived funniness mediates expected effects on attitudes and intentions. Study 1 is a quasi-experiment which uses a live medical comedy show (N = 3,964) as an entertainment education format, which either contained or did not contain information about organ donation. Study 2, a lab experiment, tests humor's causal effect in a pre-post design with a control group (N = 144) in which the same content was provided in either a humorous or non-humorous way in an audio podcast. Results showed that humorous interventions per se were not more effective than neutral information, but that informing people about organ donation in general increased donation intentions, attitudes, and knowledge. However, humorous interventions were especially effective in reducing fears related to organ donation. The findings are discussed regarding the opportunities for sensitive health communication through entertainment education formats, psychological processes that humor triggers, and humor's role in health communication formats.

Abstract Background To compare anti-VEGF treatments for macular disease in terms of costs and clinical outcomes. Methods We identified patients suffering from macular disease and treated either with aflibercept, ranibizumab or both at the largest public eye clinic in Switzerland between January 1st and December 31st 2016 who were insured in one of the two participating health insurance companies. Clinical data were extracted from the electronic health record system. The health insurers provided the health claim costs for the ophthalmologic care and the total health care costs of each patient in the observation period. Using multivariate regression models, we assessed the monthly ophthalmologic and the monthly total costs of patients with no history of switching (ranibizumab vs. aflibercept), patients with a history of switching from ranibizumab to aflibercept, patients switching during the observation period and a miscellaneous group. We examined baseline differences in age, proportion of males, visual acuity (letters), central retinal thickness (CRT) and treatment history before entering the study. We investigated treatment intensity and compared the changes in letters and CRT. Results The analysis involved 488 eyes (361 patients), 182 on ranibizumab treatment, and 63 on aflibercept treatment, 160 eyes with a history of switching from ranibizumab to aflibercept, and 45 switchers during follow-up and 38 eyes of the miscellaneous group. Compared to ranibizumab, monthly costs of ophthalmologic treatment were slightly higher for aflibercept treatment + 175.0 CHF (95%CI: 1.5 CHF to 348.3 CHF; p = 0.048) as were the total monthly costs + 581.0 CHF (95%CI: 159.5 CHF to 1002.4 CHF; p = 0.007). Compared to ranibizumab, the monthly treatment intensity with aflibercept was similar (+ 0.057 injections/month (95%CI -0.023 to 0.137; p = 0.162), corresponding to a projected annual number of 5.4 injections for ranibizumab vs. 6.1 injections for aflibercept. During follow-up, visus dropped by 0.7 letters with ranibizumab and increased by 0.6 letters with aflibercept (p = 0.243). CRT dropped by − 14.9 μm with ranibizumab and by − 19.5 μm with aflibercept (p = 0.708). The monthly costs of all other groups examined were higher. Conclusion These real-life data show that aflibercept treatment is equally expensive, and clinical outcomes between the two drugs are similar.

Abstract Background Previous analyses of real-life data indicated that injection frequency and health care costs did not differ for anti-VEGF treatment with aflibercept and ranibizumab. The objective of this study was to investigate whether this finding persisted when analysing a longer time period after licensing. Methods Retrospective analysis of health insurance claims data of two large Swiss basic health insurance plans including 28% of the Swiss population. Patients qualified for inclusion if aflibercept or ranibizumab treatment had been initiated between June 1, 2013 and November 1, 2014. Within this set, patients with at least 12 months of continuous insurance enrolment in the previous year, 12-month follow-up, and without change of anti-VEGF drug were considered. We examined the distribution of demographic data and patient characteristics between those receiving ranibizumab and those receiving aflibercept. Numbers of injections and associated health care expenditures observed during the 12-month follow-up period after incident treatment were the two outcomes considered. In multivariate regression analyses, controlling for possible confounding factors, we compared differences in these two outcomes between patients treated with aflibercept as compared to ranibizumab. Results A total of 3′058 patients were analysed, 790 (26%) receiving aflibercept and 2`268 receiving ranibizumab (74%). The use of aflibercept (average number of injections 6.2) as compared to ranibizumab (average number of injections 5.7) in the follow-up period of 1 to 12 months, was associated with a 12% increase in the injection frequency (95% confidence interval (CI) 6–17%; p

The WallDYN package has recently been applied to a number of tokamaks to self-consistently model the evolution of mixed-material plasma facing surfaces. A key component of the WallDYN model is the concentration-dependent surface sputtering rate, calculated using SDTRIM.SP. This modeled sputtering rate is strongly influenced by the surface binding energies (SBEs) of the constituent materials, which are well known for pure elements but often are poorly constrained for mixed-materials. This work examines the sensitivity of WallDYN surface evolution calculations to different models for mixed-material SBEs, focusing on the carbon/lithium/oxygen/deuterium system present in NSTX. A realistic plasma background is reconstructed from a high density, H-mode NSTX discharge, featuring an attached outer strike point with local density and temperature of 4 × 1020 m−3 and 4 eV, respectively. It is found that various mixed-material SBE models lead to significant qualitative and quantitative changes in the surface evolution profile at the outer divertor, with the highest leverage parameter being the C-Li binding model. Uncertainties of order 50%, appearing on time scales relevant to tokamak experiments, highlight the importance of choosing an appropriate mixed-material sputtering representation when modeling the surface evolution of plasma facing components. These results are generalized to other fusion-relevant materials with different ranges of SBEs.

We have studied the retention of nitrogen in surfaces with varying roughness and the transport of nitrogen from the divertor to the outer midplane in experiments at the tokamak ASDEX Upgrade. To allow for a reliable identification of nitrogen retained from the plasma exposure, 5.3 · 1021 atoms of the tracer isotope 15N were injected into the private flux region of the plasma. On polished W samples exposed to the plasma in the outer divertor, the N content peaks to both sides of the strike line with an areal density of 1.5 · 1020 15N/m2 and drops to a value of 1.0 · 1020 15N/m2 in the strike line region. In contrast, the N content of samples with a rougher surface peaks at the strike line and reaches areal densities of 3.0 · 1020 15N/m2. The N deposition at the outer limiters was measured via samples exposed on the midplane manipulator. At the limiter position the 15N areal density reaches a value of 0.2 · 1020 15N/m2, only a factor of ten smaller than the areal densities in the divertor. However, a comparison to WallDYN simulations shows that the observed N content is roughly a factor of 4 smaller than the value predicted by these simulations. Possible reasons for this discrepancy are the toroidal asymmetric main wall geometry, which currently cannot be fully included in the simulations, or an enhanced re-erosion of deposited N. Keywords: Tokamak, Impurity migration, Nitrogen, Roughness, WallDYN

Chiral domain walls in magnetic films can be electrically controlled, which makes them attractive for applications, but domain walls in ultrathin films are normally non-chiral. Here, the authors observe chiral domain walls in ultrathin Fe/Ni bilayers that are stabilized by the magnetic anisotropy.

Summary: Background: Deep learning offers considerable promise for medical diagnostics. We aimed to evaluate the diagnostic accuracy of deep learning algorithms versus health-care professionals in classifying diseases using medical imaging. Methods: In this systematic review and meta-analysis, we searched Ovid-MEDLINE, Embase, Science Citation Index, and Conference Proceedings Citation Index for studies published from Jan 1, 2012, to June 6, 2019. Studies comparing the diagnostic performance of deep learning models and health-care professionals based on medical imaging, for any disease, were included. We excluded studies that used medical waveform data graphics material or investigated the accuracy of image segmentation rather than disease classification. We extracted binary diagnostic accuracy data and constructed contingency tables to derive the outcomes of interest: sensitivity and specificity. Studies undertaking an out-of-sample external validation were included in a meta-analysis, using a unified hierarchical model. This study is registered with PROSPERO, CRD42018091176. Findings: Our search identified 31 587 studies, of which 82 (describing 147 patient cohorts) were included. 69 studies provided enough data to construct contingency tables, enabling calculation of test accuracy, with sensitivity ranging from 9·7% to 100·0% (mean 79·1%, SD 0·2) and specificity ranging from 38·9% to 100·0% (mean 88·3%, SD 0·1). An out-of-sample external validation was done in 25 studies, of which 14 made the comparison between deep learning models and health-care professionals in the same sample. Comparison of the performance between health-care professionals in these 14 studies, when restricting the analysis to the contingency table for each study reporting the highest accuracy, found a pooled sensitivity of 87·0% (95% CI 83·0–90·2) for deep learning models and 86·4% (79·9–91·0) for health-care professionals, and a pooled specificity of 92·5% (95% CI 85·1–96·4) for deep learning models and 90·5% (80·6–95·7) for health-care professionals. Interpretation: Our review found the diagnostic performance of deep learning models to be equivalent to that of health-care professionals. However, a major finding of the review is that few studies presented externally validated results or compared the performance of deep learning models and health-care professionals using the same sample. Additionally, poor reporting is prevalent in deep learning studies, which limits reliable interpretation of the reported diagnostic accuracy. New reporting standards that address specific challenges of deep learning could improve future studies, enabling greater confidence in the results of future evaluations of this promising technology. Funding: None.

Summary: Background: Deep learning has the potential to transform health care; however, substantial expertise is required to train such models. We sought to evaluate the utility of automated deep learning software to develop medical image diagnostic classifiers by health-care professionals with no coding—and no deep learning—expertise. Methods: We used five publicly available open-source datasets: retinal fundus images (MESSIDOR); optical coherence tomography (OCT) images (Guangzhou Medical University and Shiley Eye Institute, version 3); images of skin lesions (Human Against Machine [HAM] 10000), and both paediatric and adult chest x-ray (CXR) images (Guangzhou Medical University and Shiley Eye Institute, version 3 and the National Institute of Health [NIH] dataset, respectively) to separately feed into a neural architecture search framework, hosted through Google Cloud AutoML, that automatically developed a deep learning architecture to classify common diseases. Sensitivity (recall), specificity, and positive predictive value (precision) were used to evaluate the diagnostic properties of the models. The discriminative performance was assessed using the area under the precision recall curve (AUPRC). In the case of the deep learning model developed on a subset of the HAM10000 dataset, we did external validation using the Edinburgh Dermofit Library dataset. Findings: Diagnostic properties and discriminative performance from internal validations were high in the binary classification tasks (sensitivity 73·3–97·0%; specificity 67–100%; AUPRC 0·87–1·00). In the multiple classification tasks, the diagnostic properties ranged from 38% to 100% for sensitivity and from 67% to 100% for specificity. The discriminative performance in terms of AUPRC ranged from 0·57 to 1·00 in the five automated deep learning models. In an external validation using the Edinburgh Dermofit Library dataset, the automated deep learning model showed an AUPRC of 0·47, with a sensitivity of 49% and a positive predictive value of 52%. Interpretation: All models, except the automated deep learning model trained on the multilabel classification task of the NIH CXR14 dataset, showed comparable discriminative performance and diagnostic properties to state-of-the-art performing deep learning algorithms. The performance in the external validation study was low. The quality of the open-access datasets (including insufficient information about patient flow and demographics) and the absence of measurement for precision, such as confidence intervals, constituted the major limitations of this study. The availability of automated deep learning platforms provide an opportunity for the medical community to enhance their understanding in model development and evaluation. Although the derivation of classification models without requiring a deep understanding of the mathematical, statistical, and programming principles is attractive, comparable performance to expertly designed models is limited to more elementary classification tasks. Furthermore, care should be placed in adhering to ethical principles when using these automated models to avoid discrimination and causing harm. Future studies should compare several application programming interfaces on thoroughly curated datasets. Funding: National Institute for Health Research and Moorfields Eye Charity.

Deposition and fuel retention profiles in low power hydrogen L-mode plasmas and neon (Ne) seeded ITER DT burning plasmas have been investigated. Two different Ne seeded plasma backgrounds with varying sub-divertor neutral pressures but the same Ne impurity concentration are considered, representing high recycling and partially detached divertor solutions. The 2D SOLPS numerical grid does not extend all the way to the wall surfaces so that an extrapolation of the plasma background is required and is performed using a second simulation stage in which the far scrape-off layer (SOL) region is numerically gridded and plasma transport solved on the extended grid using the OSM (a 1D simplified Braginski code) approach [1]. The plasma conditions chosen for this far SOL region strongly influence the results. The hydrogenic flux is calculated from the electronic density and ion flow, the latter of which has an assumed distribution. Depending on the main-SOL plasma flow parameters and far-SOL density, fuel retention is driven by deposition on the first wall (when parallel flow through the main-SOL is switched off), or by deposition on the divertor (parallel flow through the main-SOL is switched on). When retention is dominated by deposition on the first wall, there is slightly more retention in the partially detached case compared to a high recycling scenario. In the low power cases, there is insignificant deposition and fuel retention.

Halobacterium salinarum are halophilic archaea that display directional swimming in response to various environmental signals, including light, chemicals and oxygen. In Hbt. salinarum, the building blocks (archaellins) of the archaeal swimming apparatus (the archaellum) are N-glycosylated. However, the physiological importance of archaellin N-glycosylation remains unclear. Here, a tetrasaccharide comprising a hexose and three hexuronic acids decorating the five archaellins was characterized by mass spectrometry. Such analysis failed to detect sulfation of the hexuronic acids, in contrast to earlier reports. To better understand the physiological significance of Hbt. salinarum archaellin N-glycosylation, a strain deleted of aglB, encoding the archaeal oligosaccharyltransferase, was generated. In this ΔaglB strain, archaella were not detected and only low levels of archaellins were released into the medium, in contrast to what occurs with the parent strain. Mass spectrometry analysis of the archaellins in ΔaglB cultures did not detect N-glycosylation. ΔaglB cells also showed a slight growth defect and were impaired for motility. Quantitative real-time PCR analysis revealed dramatically reduced transcript levels of archaellin-encoding genes in the mutant strain, suggesting that N-glycosylation is important for archaellin transcription, with downstream effects on archaellum assembly and function. Control of AglB-dependent post-translational modification of archaellins could thus reflect a previously unrecognized route for regulating Hbt. salinarum motility.

Different weak organic acids have significant potential as topical treatments for wounds infected by opportunistic pathogens that are recalcitrant to standard treatments. These acids have long been used as bacteriostatic compounds in the food industry, and in some cases are already being used in the clinic. The effects of different organic acids vary with pH, concentration, and the specific organic acid used, but no studies to date on any opportunistic pathogens have examined the detailed interactions between these key variables in a controlled and systematic way. We have therefore comprehensively evaluated the effects of several different weak organic acids on growth of the opportunistic pathogen Pseudomonas aeruginosa. We used a semi-automated plate reader to generate growth profiles for two different strains (model laboratory strain PAO1 and clinical isolate PA1054 from a hospital burns unit) in a range of organic acids at different concentrations and pH, with a high level of replication for a total of 162,960 data points. We then compared two different modeling approaches for the interpretation of this time-resolved dataset: parametric logistic regression (with or without a component to include lag phase) vs. non-parametric Gaussian process (GP) regression. Because GP makes no prior assumptions about the nature of the growth, this method proved to be superior in cases where growth did not follow a standard sigmoid functional form, as is common when bacteria grow under stress. Acetic, propionic and butyric acids were all more detrimental to growth than the other acids tested, and although PA1054 grew better than PAO1 under non-stress conditions, this difference largely disappeared as the levels of stress increased. As expected from knowledge of how organic acids behave, their effect was significantly enhanced in combination with low pH, with this interaction being greatest in the case of propionic acid. Our approach lends itself to the characterization of combinatorial interactions between stressors, especially in cases where their impacts on growth render logistic growth models unsuitable.

The Dzyaloshinskii-Moriya interaction (DMI) has drawn much attention, as it stabilizes magnetic chirality, with important implications in fundamental and applied research. This antisymmetric exchange interaction is induced by the broken inversion symmetry at interfaces or in noncentrosymmetric lattices. Significant interfacial DMIs are often found at magnetic/heavy-metal interfaces with large spin-orbit coupling. Recent studies have shown promise for induced DMI at interfaces involving light elements such as carbon (graphene) or oxygen. Here, we report direct observation of induced DMI by chemisorption of the lightest element, hydrogen, on a ferromagnetic layer at room temperature, which is supported by density functional theory calculations. We further demonstrate a reversible chirality transition of the magnetic domain walls due to the induced DMI via hydrogen chemisorption and desorption. These results shed new light on the understanding of DMI in low atomic number materials and the design of novel chiral spintronics and magneto-ionic devices.