Curie temperature and carrier concentration gradients in MBE grown GaMnAs layers

We report on detailed investigations of the electronic and magnetic properties of ferromagnetic GaMnAs layers, which have been fabricated by low-temperature molecular-beam epitaxy. Superconducting quantum interference device measurements reveal a decrease of the Curie temperature from the surface to the GaMnAs/GaAs interface. While high resolution x-ray diffraction clearly shows a homogeneous Mn distribution, a pronounced decrease of the carrier concentration from the surface towards the GaMnAs/GaAs interface has been found by Raman spectroscopy as well as electrochemical capacitance-voltage profiling. The gradient in Curie temperature seems to be a general feature of GaMnAs layers grown at low-temperature. Possible explanations are discussed.Comment: 3 pages, 4 figures, submitted to AP

Bottom-up assembly of metallic germanium

Extending chip performance beyond current limits of miniaturisation requires new materials and functionalities that integrate well with the silicon platform. Germanium fits these requirements and has been proposed as a high-mobility channel material, a light emitting medium in silicon-integrated lasers, and a plasmonic conductor for bio-sensing. Common to these diverse applications is the need for homogeneous, high electron densities in three-dimensions (3D). Here we use a bottom-up approach to demonstrate the 3D assembly of atomically sharp doping profiles in germanium by a repeated stacking of two-dimensional (2D) high-density phosphorus layers. This produces high-density (1019 to 1020 cm-3) low-resistivity (10-4Ω ∙ cm) metallic germanium of precisely defined thickness, beyond the capabilities of diffusion-based doping technologies. We demonstrate that free electrons from distinct 2D dopant layers coalesce into a homogeneous 3D conductor using anisotropic quantum interference measurements, atom probe tomography, and density functional theory

Gold and silver diffusion in germanium: a thermodynamic approach

Diffusion properties are technologically important in the understanding of semiconductors for the efficent formation of defined nanoelectronic devices. In the present study we employ experimental data to show that bulk materials properties (elastic and expansivity data) can be used to describe gold and silver diffusion in germanium for a wide temperature range (702–1177 K). Here we show that the so-called cBΩ model thermodynamic model, which assumes that the defect Gibbs energy is proportional to the isothermal bulk modulus and the mean volume per atom, adequately metallic diffusion in germanium

Integrate mechanistic evidence from new approach methodologies (NAMs) into a read-across assessment to characterise trends in shared mode of action

This read-across case study characterises thirteen, structurally similar carboxylic acids demonstrating the application of in vitro and in silico human-based new approach methods, to determine biological similarity. Based on data from in vivo animal studies, the read-across hypothesis is that all analogues are steatotic and so should be considered hazardous. Transcriptomic analysis to determine differentially expressed genes (DEGs) in hepatocytes served as first tier testing to confirm a common mode-of-action and identify differences in the potency of the analogues. An adverse outcome pathway (AOP) network for hepatic steatosis, informed the design of an in vitro testing battery, targeting AOP relevant MIEs and KEs, and Dempster-Shafer decision theory was used to systematically quantify uncertainty and to define the minimal testing scope. The case study shows that the read-across hypothesis is the critical core to designing a robust, NAM-based testing strategy. By summarising the current mechanistic understanding, an AOP enables the selection of NAMs covering MIEs, early KEs, and late KEs. Experimental coverage of the AOP in this way is vital since MIEs and early KEs alone are not confirmatory of progression to the AO. This strategy exemplifies the workflow previously published by the EUTOXRISK project driving a paradigm shift towards NAM-based NGRA.Toxicolog

PBPK modeling of zebrafish embryo for reprotoxicity assessment of valproic acid and some of its analogs

Introduction: Understanding and predicting chemical effects on development and reproduction is a complex challenge. The zebrafish embryo is an in vitro test system increasingly used for its transparency, short development time, easy husbandry and gene homologies with humans. Objectives: To better explain and predict developmental toxic effects observed in zebrafish embryo, we are developing a generic physiologically-based pharmacokinetic (PBPK) model to predict target organ concentrations of neutral or ionizable chemicals. We present an application of the model in the assessment of the teratogenicity of valproic acid (VPA) and nine analogs. Material and Methods: Quasi steady-state distribution of chemicals is modeled in ten embryo organs, and in two sub-cellular organelles: lysosomes and mitochondria. The partition coefficients between the organs or organelles and the culture medium depend on physico-chemical properties of the substances. Organ volumes grow over the first 5 days of life. Liver metabolism can be linear or saturable. For VPA and analogs, metabolic parameters were estimated by Bayesian fitting of the model to data on culture medium and embryo concentrations during repeated dosing. Results: The kinetic data were reasonably well fitted by the model (Figure 1), even though residual uncertainty was substantial. Linear clearance estimates for VPA and analogs were around 10-10 to 10-11L/min, which for an embryo volume of 3×10-7L, correspond to half-lives of about 11.5h. Embryo organ concentrations were used to calculate dose-response for general lethality and heart defectcaused deaths. Naïve dose-responses were also calculated using nominal dose. Using target organ concentrations shifts substantially the magnitude of dose-response parameters and the relative toxicity ranking of the VPA analogs studied (Figure 2). Conclusion: The model can be used to relate zebrafish effects observed in vitro to cellular exposures. It should improve the translation of in vitro zebrafish data to humans for safety assessment

Outcomes for Infants Born in Perinatal Centers Performing Fewer Surgical Ligations for Patent Ductus Arteriosus: A Swiss Population-Based Study

Objective To assess patent ductus arteriosus treatment variation between Swiss perinatal centers and to determine its effect on outcome in a population-based setting. Study design This was a retrospective cohort study of infants born less than 28 weeks of gestation between 2012 and 2017. Outcomes between surgically ligated and pharmacologically treated infants as well as infants born in centers performing ≤10% ligation (“low” group) and >10% (“high” group) were compared using logistic regression and 1:1 propensity score matching. Matching was based on case-mix and preligation confounders: intraventricular hemorrhages grades 3-4, necrotizing enterocolitis, sepsis, and ≥28 days’ oxygen supply. Results Of 1389 infants, 722 (52%) had pharmacologic treatment and 156 (11.2%) received surgical ligation. Compared with infants who received pharmacologic treatment, ligated infants had greater odds for major morbidities (OR 2.09, 95% CI 1.44-3.04) and 2-year neurodevelopmental impairment (OR 1.81, 95% CI 1.15-2.84). Mortality was comparable after restricting the cohort to infants surviving at least until day 10 to avoid survival bias. In the “low” group, 34 (4.9%) of 696 infants were ligated compared with 122 (17.6%) of 693 infants in the “high” group. Infants in the “high” group had greater odds for major morbidities (OR 1.49, 95% CI 1.11-2.0). Conclusions Our analysis identified a burden on infants receiving surgical ligation vs pharmacologic treatment in a population-based setting where there was no agreed-on common procedure. These results may guide a revision of patent ductus arteriosus treatment practice in Switzerland