Bridging the gap between particle-scale forces and continuum modelling of size segregation: application to bedload transport

Gravity-driven size segregation is important in mountain streams where a wide range of grain sizes are transported as bedload. More particularly, vertical size segregation is a multi-scale process that originates in interactions at the scale of particles with important morphological consequences on the reach scale. To address this issue, a volume-averaged multi-phase flow model for immersed bidisperse granular flows was developed based on an interparticle segregation force (Guillard et al. 2016) and a granular Stokesian drag force (Tripathi and Khakhar 2013). An advection-diffusion model was derived from this model yielding parametrisations for the advection and diffusion coefficients based on the interparticle interactions. This approach makes it possible to bridge the gap between grain-scale physics and continuum modelling. Both models were successfully tested against existing Discrete Element Model (DEM) simulations of size segregation in bedload transport (Chassagne et al. 2020). Through a detailed investigation of the granular forces, it is demonstrated that the observed scaling of the advection and diffusion coefficients with the inertial number can be explained by the granular drag force dependency on the viscosity. The drag coefficient was shown to be linearly dependent on the small particle concentration. The scaling relationship of the segregation force with the friction coefficient is confirmed and additional non-trivial dependencies including the inertial number and small particle concentration are identified. Lastly, adding a size ratio dependency in the segregation force perfectly reproduces the DEM results for a large range of small particle concentrations and size-ratios

On granular rheology in bedload transport

The local granular phase rheology in bedload transport is investigated from discrete numerical simulations. The numerical model is based on a coupled Discrete Element Method with a 1D space-averaged fluid momentum balance. Using this model the averaged granular stress tensor profile can be computed from particle-particle interactions. In bed-load transport, the granular media exhibits quasi-static and dynamical behaviors. This physical situation can be used as a rheometer and the actual granular rheology can be deduced from a single simulation. Preliminary results suggests that the denser part of the flow, close to the static bed, is well described by a a μ(I)/Φ(I) rheology. Above this layer, the dense granular flow rheology fails to explain the observed shear and normal stresses, meaning that other mechanisms come into play

Looking back: twenty years of reforming undergraduate medical training and curriculum frameworks in Switzerland

Introduction: To date, hardly any reports exist that outline the reforms in medical studies in Switzerland from the first partial reforms in the 1970s until today.Methods: This article outlines the recent history of medical curricula, their reforms in the early 1970s and, based on these, the key reasons for the major curricular reforms of the 2000s from the perspective of the authors.Results: The various projects, initiatives and legislative elements at the national level include the introduction of new quality control instruments – federal examination and programme accreditation, the introduction of a national catalogue of learning objectives and its two follow-up editions, as well as the implementation of the Bologna reform in undergraduate medical curricula. Examples of the key new elements found in all medical training in Switzerland include: the interdisciplinary orientation of learning content in organ and functional system-oriented subject areas or modules, the enhanced valorisation of practical clinical training, as well as the introduction of problem-oriented formats and the integration of partly formative, partly summative exams according to the format of the objective structured practical examination (OSCE). Characteristics unique to the four medical faculties and their medical training programme are also highlighted.Discussion: The described projects, initiatives and legislative elements have led to a dynamic, continuous development of medical curricula in Switzerland. The close cooperation between the faculties and the Federal Office of Public Health (FOPH) has also resulted in a redefinition of the roles and responsibilities of universities and the Federal Government according to the new Law on Medical Professions. This guarantees the medical faculties a great deal of autonomy, without neglecting quality assurance.Einleitung: Bisher existieren kaum Berichte, die die Schweizer Reformen des Medizinstudiums von den ersten Teilreformen in den 1970er Jahren bis heute skizzieren. Methoden: In der vorliegenden Arbeit werden kursorisch die jüngere Geschichte der humanmedizinischen Curricula, deren erste Teilreformen in den frühen 1970er Jahren und darauf aufbauend die wesentlichen Ausgangspunkte für die grossen Curriculumsreformen der 2000er Jahre aus Sicht der Autoren beschrieben. Ergebnisse: Die vielfältigen Projekte, Initiativen und gesetzgebenden Elemente auf Eidgenössischer Ebene umfassen die Einführung von neuen Qualitätsentwicklungsinstrumenten – Eidgenössische Prüfung und Programmakkreditierung, die Einführung und Weiterentwicklung eines nationalen Lernzielkataloges über insgesamt drei Editionen sowie die Einführung der Bologna Reformen auch in den humanmedizinischen Studiengängen. Im Sinne der Entwicklung von ausdifferenzierten Modellstudiengängen können exemplarisch die wesentlichen neuen Elemente aller Studiengänge in der Schweiz charakterisiert werden: die interdisziplinäre Ausrichtung der Lerninhalte in organ- und funktionssystem-orientierten Themenblöcken oder Modulen, die Aufwertung der klinisch-praktischen Ausbildung sowie die Einführung von problem-orientierten Formaten und der Integration von teils formativen, teils summativen Prüfungen nach dem OSCE-Format. Aufgezeigt werden auch die besonderen standort-spezifischen Charakteristika von vier Medizinischen Fakultäten und deren humanmedizinischen Studiengängen. Diskussion: Die beschriebenen Projekte, Initiativen und gesetzgebenden Elemente haben in der Schweiz zu einer dynamischen, weiterhin anhaltenden Entwicklung der humanmedizinischen Curricula geführt. Die enge Zusammenarbeit zwischen den Fakultäten und dem Bundesamt für Gesundheit (BAG) hat zudem bewirkt, dass mit dem neuen Medizinalberufegesetz Rollen und Verantwortungen zwischen Universitäten und Bund neu definiert worden sind. Dies gewährleistet den Fakultäten eine grosse Autonomie ohne die Qualitätssicherung zu vernachlässigen

JAK2 Unmutated Polycythaemia-Real-World Data of 10 Years from a Tertiary Reference Hospital.

(1) Background: Polycythaemia is defined by an increase in haemoglobin (Hb) concentration, haematocrit (Hct) or red blood cell (RBC) count above the reference range adjusted to age, sex and living altitude. JAK2 unmutated polycythaemia is frequent but under-investigated in original publications. In this retrospective cohort study, we investigated the clinical and laboratory data, underlying causes, management and outcomes of JAK2 unmutated polycythaemia patients. (2) Methods: The hospital database was searched to identify JAK2 unmutated patients fulfilling WHO 2016 Hb/Hct criteria for PV (Hb >16.5 g/dL in men and >16 g/dL in women, or Hct > 49% in men and >48% in women, or RBC mass > 25% above mean normal predicted value) between 2008 and 2019. Clinical and laboratory data were collected and analysed. (3) Results: From 727,731 screened patients, 294 (0.04%) were included, the median follow-up time was 47 months. Epo and P50 showed no clear pattern in differentiating causes of polycythaemia. In 30%, the cause remained idiopathic, despite extensive work-up. Sleep apnoea was the primary cause, also in patients under 30. Around 20% had received treatment at any time, half of whom had ongoing treatment at the end of follow-up. During follow-up, 17.2% developed a thromboembolic event, of which 8.5% were venous and 8.8% arterial. The mortality was around 3%. (4) Conclusions: Testing for Epo and P50 did not significantly facilitate identification of underlying causes. The frequency of sleep apnoea stresses the need to investigate this condition. Idiopathic forms are common. A diagnostic flowchart based on our data is proposed here. NGS testing should be considered in young patients with persisting polycythaemia, irrespective of Epo and P50 levels

B(H) Constitutive Relations Near H_c1 in Disordered Superconductors

We provide a self-contained account of the B vs. H constitutive relation near H_c1 in Type II superconductors with various types of quenched random disorder. The traditional Abrikosov result B ~ [ln (H - H_c1)]^{-2}, valid in the absence of disorder and thermal fluctuations, changes significantly in the presence of disorder. Moreover, the constitutive relations will depend strongly on the type of disorder. In the presence of point disorder, B ~ (H - H_c1)^{3/2} in three-dimensional (thick) superconductors, as shown by Nattermann and Lipowsky. In two-dimensional (thin film) superconductors with point disorder, B ~ (H - H_c1). In the presence of parallel columnar disorder, we find that B ~ exp[-C / (H - H_c1)] in three dimensions, while B ~ exp[-K / (H - H_c1)^{1/2}] in two dimensions. In the presence of nearly isotropically splayed disorder, we find that B ~ (H - H_c1)^{3/2} in both two and three dimensions.Comment: 37 pages, 12 figures included in text; submitted to Physica

Phase-field-crystal models for condensed matter dynamics on atomic length and diffusive time scales: an overview

Here, we review the basic concepts and applications of the phase-field-crystal (PFC) method, which is one of the latest simulation methodologies in materials science for problems, where atomic- and microscales are tightly coupled. The PFC method operates on atomic length and diffusive time scales, and thus constitutes a computationally efficient alternative to molecular simulation methods. Its intense development in materials science started fairly recently following the work by Elder et al. [Phys. Rev. Lett. 88 (2002), p. 245701]. Since these initial studies, dynamical density functional theory and thermodynamic concepts have been linked to the PFC approach to serve as further theoretical fundaments for the latter. In this review, we summarize these methodological development steps as well as the most important applications of the PFC method with a special focus on the interaction of development steps taken in hard and soft matter physics, respectively. Doing so, we hope to present today's state of the art in PFC modelling as well as the potential, which might still arise from this method in physics and materials science in the nearby future.Comment: 95 pages, 48 figure

Vortex Pinning and the Non-Hermitian Mott Transition

The boson Hubbard model has been extensively studied as a model of the zero temperature superfluid/insulator transition in Helium-4 on periodic substrates. It can also serve as a model for vortex lines in superconductors with a magnetic field parallel to a periodic array of columnar pins, due to a formal analogy between the vortex lines and the statistical mechanics of quantum bosons. When the magnetic field has a component perpendicular to the pins, this analogy yields a non-Hermitian boson Hubbard model. At integer filling, we find that for small transverse fields, the insulating phase is preserved, and the transverse field is exponentially screened away from the boundaries of the superconductor. At larger transverse fields, a ``superfluid'' phase of tilted, entangled vortices appears. The universality class of the transition is found to be that of vortex lines entering the Meissner phase at H_{c1}, with the additional feature that the direction of the tilted vortices at the transition bears a non-trivial relationship to the direction of the applied magnetic field. The properties of the Mott Insulator and flux liquid phases with tilt are also discussed.Comment: 20 pages, 12 figures included in text; to appear in Physical Review

External Validation and Extension of a Clinical Score for the Discrimination of Type 2 Myocardial Infarction

Background: The early non-invasive discrimination of Type 2 versus Type 1 Myocardial Infarction (T2MI, T1MI) is a major unmet clinical need. We aimed to externally validate a recently derived clinical score (Neumann) combing female sex, no radiating chest pain, and high-sensitivity cardiac troponin I (hs-cTnI) concentration ≤40.8 ng/L. Methods: Patients presenting with acute chest discomfort to the emergency department were prospectively enrolled into an international multicenter diagnostic study. The final diagnoses of T2MI and T1MI were centrally adjudicated by two independent cardiologists using all information including cardiac imaging and serial measurements of hs-cTnT/I according to the fourth universal definition of MI. Model performance for T2MI diagnosis was assessed by formal tests and graphical means of discrimination and calibration. Results: Among 6684 enrolled patients, MI was the adjudicated final diagnosis in 1079 (19%) patients, of which 242 (22%) had T2MI. External validation of the Neumann Score showed a moderate discrimination (C-statistic 0.67 (95%CI 0.64–0.71)). Model calibration showed underestimation of the predicted probabilities of having T2MI for low point scores. Model extension by adding the binary variable heart rate >120/min significantly improved model performance (C-statistic 0.73 (95% CI 0.70–0.76, p 120/min improved the model’s performance

Exploring the Chemical Properties and Medicinal Applications of Tetramethylthiocycloheptyne Sulfoximine Used in Strain-Promoted Azide–Alkyne Cycloaddition Reactions

The recently developed compound, tetramethylthiocycloheptyne sulfoximine (TMTHSI), has shown to be a promising strained alkyne for strain-promoted azide–alkyne cycloaddition (SPAAC), metal-free click chemistry. This research explores the properties of TMTHSI-based compounds via three aspects: (1) large-scale production, (2) unique stability in acidic conditions and its subsequent use in peptide synthesis, and (3) the functionalization of antibodies. Here, it is shown that (1) scale-up is achieved on a scale of up to 100 g. (2) TMTHSI is remarkably stable against TFA allowing for the site-specific functionalization of peptides on resin. Finally, (3) the functionalization of an antibody with a model payload is very efficient, with antibody conjugation demonstrating more beneficial features such as a high yield and limited hydrophobicity as compared to other alkyne reagent conjugates. These results illustrate the high potential of TMTHSI for diverse bioconjugation applications, with production already being GMP-compatible and a highly efficient conversion resulting in attractive costs of goods

Rahmenkonzept der Universitäten des Landes Baden-Württemberg für das High-Performance Computing (HPC) und Data-Intensive Computing (DIC) für den Zeitraum 2025 bis 2032

Digitale Infrastrukturen und darauf aufsetzende Dienste bilden inzwischen in fast allen Fachgebieten das Rückgrat wissenschaftlicher Forschung. Deshalb muss die strategische Zielsetzung eines HPCKonzepts klare Antworten auf eine Vielzahl von Problemstellungen finden. Dazu zählen die stetige Zunahme digitaler Workflows, bedingt beispielsweise durch die Verbesserung des Instrumentariums in den Naturwissenschaften, neue Forschungsansätze in den Digital Humanities, die Verfeinerung der Auflösung in bildgebenden Verfahren, aber auch der zunehmende Einsatz Künstlicher Intelligenz in immer breiteren Anwendungsfeldern. Öffentlich geförderte und betriebene Forschungsinfrastrukturen sind hier von entscheidender Bedeutung. Föderierte Strukturen erzeugen Synergien und haben klare strategische Vorteile gegenüber vereinzelten Insellösungen, insbesondere im Bereich High-Performance-Computing/Data Intensive Computing (HPC-DIC). Daher müssen sie im Interesse der Nutzenden auf der lange etablierten Basis verlässlich, zukunftssicher und nachhaltig weiterentwickelt werden. Im Sinne des Wissenschafts- und Wirtschaftsstandorts Baden-Württemberg sollen sie eine für Menschen gemachte Digitalisierung voranbringen, moderne technische Entwicklungen mitgestalten, zusätzliche Kreativität freisetzen, und nicht zuletzt die breite Verteilung von Kompetenzen unterstützen. Basierend auf internationalen Standards sind digitale Dienste auf allen Ebenen (lokal, regional, national und international) geeignet zu vernetzen. Um den Standort Baden-Württemberg weiter attraktiv für Forscher, Entwickler und Dienstleister auszubauen, ist dies eine unverzichtbare Voraussetzung. Die Hochschulen im Land müssen sich im Hinblick auf die Anwerbung von IT-Fachkräften zu einem begehrten Arbeitgeber weiterentwickeln