Dynamics and energetics of emergent magnetic monopoles in chiral magnets

The formation and destruction of topologically quantized magnetic whirls, so-called skyrmions, in chiral magnets is driven by the creation and motion of singular hedgehog defects. These can be identified with emergent magnetic monopoles and antimonopoles. We investigate how the energetics of and forces between monopoles and antimonopoles influence their creation rate and dynamics. We study a single skyrmion line defect in the helical phase using both micromagnetic simulations and a Ginzburg-Landau analysis. Monopole-antimonople pairs are created in a thermally activated process, largely controlled by the (core) energy of the monopole. The force between monopoles and antimonopoles is linear in distance and described by a string tension. The sign and size of the string tension determines the stability of the phases and the velocity of the monopoles.Comment: 4 pages, 5 figure

Inertia, diffusion and dynamics of a driven skyrmion

Skyrmions recently discovered in chiral magnets are a promising candidate for magnetic storage devices because of their topological stability, small size ($\sim 3-100$nm), and ultra-low threshold current density ($\sim 10^{6}$A/m$^2$) to drive their motion. However, the time-dependent dynamics has hitherto been largely unexplored. Here we show, by combining the numerical solution of the Landau-Lifshitz-Gilbert equation and the analysis of a generalized Thiele's equation, that inertial effects are almost completely absent in skyrmion dynamics driven by a time-dependent current. In contrast, the response to time-dependent magnetic forces and thermal fluctuations depends strongly on frequency and is described by a large effective mass and a (anti-) damping depending on the acceleration of the skyrmion. Thermal diffusion is strongly suppressed by the cyclotron motion and is proportional to the Gilbert damping coefficient $\alpha$. This indicates that the skyrmion position is stable, and its motion responds to the time-dependent current without delay or retardation even if it is fast. These findings demonstrate the advantages of skyrmions as information carriers.Comment: 9 pages, 10 figure

Skyrmions and Monopoles in Chiral Magnets & Correlated Heterostructures

The first part of this thesis is called "Skyrmions and Monopoles in Chiral Magnets" and concerned with topological spin textures in chiral magnets. The second part, "Correlated Heterostructures", studies layered, strongly correlated devices within the framework of dynamical mean-field theory. In magnets without inversion symmetry, so called chiral magnets, weak spin-orbit coupling leads to the formation of smooth twisted magnetic structures with a long period. Recently, a new magnetic phase of a lattice of topologically stable whirl-lines was discovered. In the first chapter we introduce the concept of a such a whirling texture and briefly mention its occurrence in other areas of physics. In chapters 2 we review the Ginzburg-Landau theory for chiral magnetic structures describing their equilibrium properties followed by a description of a numerical minimisation technique to explore the mean-field configuration of the free energy functional. In chapter 3 we review the Langevin description for a system at finite temperature and concentrate on especially on the description of magnetic systems. The describe how a numerical integration of the equations of motion, a stochastically differential equation, can be achieved to compute ensemble-averaged quantities. Chapter 4 we present the discovery of emergent magnetic monopoles as the driving mechanism behind topological phase transitions from the Skyrmion lattice into topologically trivial phases. We describe how a Skyrmion lattice unwinds due to the motion of magnetic monopoles in the system as seen both in experiment and numerical simulations. We investigate how the energetics of and forces between monopoles and antimonopoles influence their creation rate and dynamics. In chapter 5 we turn to the dynamical properties of single Skyrmions in ferromagnetic backgrounds. In a first approach we study analytically the fluctuations around the mean-field configuration and determine the spectrum of the bound states, the scattering solutions and their phase shifts and coupling mechanism to the collective Skyrmion coordinate. By integrating out the fluctuations we discover a strongly frequency-dependent effective mass for the collective Skyrmion coordinate. We approach the same question from a different angle in the second part of the chapter. Here we start from numerical simulations of the stochastic Landau-Lifshitz-Gilbert equation and determine the coefficients of the effective equations of motion from a statistical analysis of the collective coordinate fluctuations. We find a strongly frequency-dependent effective mass and a new peculiar damping mechanism proportional to the acceleration of the Skyrmion that we call 'gyro-damping'. The second part of this thesis explores the interface effects in strongly correlated heterostructures. Multilayered heterostructures in the nano sized realm (also known as multilayered nanostructures) are the most common electronic devices. A classic multilayered nanostructure is a tunnel junction consisting of two metallic leads connected by a ``weak link'', often a conventional band insulator. The connection between the two leads is thus governed by inherently quantum mechanical effects. We begin with an introduction to model Hamiltonians, in particular the Hubbard and the single impurity Anderson model. The second chapter describes the static mean-field treatment of anti-ferromagnetic order in the Hubbard model. Chapter 3 introduces the reader to the dynamical mean-field theory (DMFT) and describes extensions of the DMFT to system with antiferromagnetic order. The DMFT maps the lattice problem onto an effective impurity problem. In chapter 4 we review how the single impurity Anderson model can be solved using the numerical renormalisation group (NRG). The generalisation of DMFT to inhomogenous, layered systems is given in chapter 5 including the effects of long-range Coulomb interactions on the Hartree level. Here we also outline our generalisation of the inhomogenous DMFT to systems with antiferromagnetic order. In chapter 6 we derive expressions for the layer-resolved optical conductivity and the Hall conductivity. We apply the former to the Mott-Band-Mott heterostructure where we study the transport properties of the two-dimensional metallic state at the interface where we find a rich temperature dependence. In chapter 7 we turn to the question how the transmission amplitude through a Mott insulator in a linear potential depends on temperature

The Nitrogen Content in the Fruiting Body and Mycelium of Pleurotus Ostreatus and Its Utilization as a Medium Component in Thraustochytrid Fermentation

Following the idea of a circular bioeconomy, the use of side streams as substitutes for cultivation media (components) in bioprocesses would mean an enormous economic and ecological advantage. Costly compounds in conventional media for the production of the triterpene squalene in thraustochytrids are the main carbon source and complex nitrogen sources. Among other side streams examined, extracts from the spent mycelium of the basidiomycete Pleurotus ostreatus were best-suited to acting as alternative nitrogen sources in cultivation media for thraustochytrids. The total nitrogen (3.76 ± 0.01 and 4.24 ± 0.04%, respectively) and protein (16.47 ± 0.06 and 18.57 ± 0.18%, respectively) contents of the fruiting body and mycelium were determined. The fungal cells were hydrolyzed and extracted to generate accessible nitrogen sources. Under preferred conditions, the extracts from the fruiting body and mycelium contained 73.63 ± 1.19 and 89.93 ± 7.54 mM of free amino groups, respectively. Cultivations of Schizochytrium sp. S31 on a medium using a mycelium extract as a complex nitrogen source showed decelerated growth but a similar squalene yield (123.79 ± 14.11 mg/L after 216 h) compared to a conventional medium (111.29 ± 19.96 mg/L, although improvable by additional complex nitrogen source)

Two α subunits and one β subunit of meprin zinc-endopeptidases are differentially expressed in the zebrafish Danio rerio

Meprins are members of the astacin family of metalloproteases expressed in epithelial tissues, intestinal leukocytes and certain cancer cells. In mammals, there are two homologous subunits, which form complex glycosylated disulfide-bonded homo- and heterooligomers. Both human meprin α and meprin β cleave several basement membrane components, suggesting a role in epithelial differentiation and cell migration. There is also evidence that meprin β is involved in immune defence owing to its capability of activating interleukin-1β and the diminished mobility of intestinal leukocytes in meprin β-knockout mice. Here we show for the first time by reverse transcription PCR, immunoblotting and immunofluorescence analyses that meprins are expressed not only in mammals, but also in the zebrafish Danio rerio. In contrast to the human, mouse and rat enzymes, zebrafish meprins are encoded by three genes, corresponding to two homologous α subunits and one β subunit. Observations at both the mRNA and protein level indicate a broad distribution of meprins in zebrafish. However, there are strikingly different expression patterns of the three subunits, which is consistent with meprin expression in mammals. Hence, D. rerio appears to be a suitable model to gain insight into the basic physiological functions of meprin metalloprotease

Novel multi-objective affinity approach allows to identify pH-specific μ-opioid receptor agonists

Opioids are essential pharmaceuticals due to their analgesic properties, however, lethal side effects, addiction, and opioid tolerance are extremely challenging. The development of novel molecules targeting the -opioid receptor (MOR) in inflamed, but not in healthy tissue, could significantly reduce these unwanted effects. Finding such novel molecules can be achieved by maximizing the binding affinity to the MOR at acidic pH while minimizing it at neutral pH, thus combining two conflicting objectives. Here, this multi-objective optimal affinity approach is presented, together with a virtual drug discovery pipeline for its practical implementation. When applied to finding pH-specific drug candidates, it combines protonation state-dependent structure and ligand preparation with high-throughput virtual screening. We employ this pipeline to characterize a set of MOR agonists identifying a morphine-like opioid derivative with higher predicted binding affinities to the MOR at low pH compared to neutral pH. Our results also confirm existing experimental evidence that NFEPP, a previously described fentanyl derivative with reduced side effects, and recently reported -fluorofentanyls and -morphines show an increased specificity for the MOR at acidic pH when compared to fentanyl and morphine. We further applied our approach to screen a >50K ligand library identifying novel molecules with pH-specific predicted binding affinities to the MOR. The presented differential docking pipeline can be applied to perform multi-objective affinity optimization to identify safer and more specific drug candidates at large scale

Let It Flow: Morpholino Knockdown in Zebrafish Embryos Reveals a Pro-Angiogenic Effect of the Metalloprotease Meprin α2

BACKGROUND: Meprin metalloproteases are thought to be involved in basic physiological functions such as cell proliferation and tissue differentiation. However, the specific functions of these enzymes are still ambiguous, although a variety of growth factors and structural proteins have been identified as meprin substrates. The discovery of meprins alpha(1), alpha(2) and beta in teleost fish provided the basis for uncovering their physiological functions by gene silencing in vivo. METHODOLOGY/PRINCIPAL FINDINGS: A Morpholino knockdown in zebrafish embryos targeting meprin alpha(1) and beta mRNA caused defects in general tissue differentiation. But meprin alpha(2) morphants were affected more specifically and showed severe failures in the formation of the vascular system provoking the hypothesis of a pro-angiogenic effect. The blood circulation was largely diminished resulting in erythrocyte accumulation. These phenotypes mimic a previously described VEGF-A morphant, revealing a possible role of meprin alpha in VEGF-A activation. Indeed, human recombinant meprin alpha processed the vascular endothelial growth factor-A (VEGF-A) specifically, revealing the same cleavage products detectable for VEGF from zebrafish whole lysate. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that meprin metalloproteases are important for cell differentiation and proliferation already during embryogenesis, predominantly by the activation of growth factors. Thus, we conclude that meprins play a significant role in VEGF-A processing, subsequently regulating angiogenesis. Therefore, meprin alpha might be a new therapeutic target in cardiovascular diseases or in tumor growth inhibition

Markov State Models from short non-Equilibrium Simulations - Analysis and Correction of Estimation Bias

Many state-of-the-art methods for the thermodynamic and kinetic characterization of large and complex biomolecular systems by simulation rely on ensemble approaches, where data from large numbers of relatively short trajectories are integrated. In this context, Markov state models (MSMs) are extremely popular because they can be used to compute stationary quantities and long-time kinetics from ensembles of short simulations, provided that these short simulations are in “local equilibrium” within the MSM states. However, over the last 15 years since the inception of MSMs, it has been controversially discussed and not yet been answered how deviations from local equilibrium can be detected, whether these deviations induce a practical bias in MSM estimation, and how to correct for them. In this paper, we address these issues: We systematically analyze the estimation of MSMs from short non-equilibrium simulations, and we provide an expression for the error between unbiased transition probabilities and the expected estimate from many short simulations. We show that the unbiased MSM estimate can be obtained even from relatively short non-equilibrium simulations in the limit of long lag times and good discretization. Further, we exploit observable operator model (OOM) theory to derive an unbiased estimator for the MSM transition matrix that corrects for the effect of starting out of equilibrium, even when short lag times are used. Finally, we show how the OOM framework can be used to estimate the exact eigenvalues or relaxation time scales of the system without estimating an MSM transition matrix, which allows us to practically assess the discretization quality of the MSM. Applications to model systems and molecular dynamics simulation data of alanine dipeptide are included for illustration. The improved MSM estimator is implemented in PyEMMA of version 2.3

PROGRESS – prospective observational study on hospitalized community acquired pneumonia

Background: Community acquired pneumonia (CAP) is a high incidence disease resulting in about 260,000 hospital admissions per year in Germany, more than myocardial infarction or stroke. Worldwide, CAP is the most frequent infectious disease with high lethality ranging from 1.2 % in those 20–29 years old to over 10 % in patients older than 70 years, even in industrial nations. CAP poses numerous medical challenges, which the PROGRESS (Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Sepsis) network aims to tackle: Operationalization of disease severity throughout the course of disease, outcome prediction for hospitalized patients and prediction of transitions from uncomplicated CAP to severe CAP, and finally, to CAP with sepsis and organ failure as a life-threatening condition. It is a major aim of PROGRESS to understand and predict patient heterogeneity regarding outcome in the hospital and to develop novel treatment concepts. Methods: PROGRESS was designed as a clinical, observational, multi-center study of patients with CAP requiring hospitalization. More than 1600 patients selected for low burden of co-morbidities have been enrolled, aiming at a total of 3000. Course of disease, along with therapy, was closely monitored by daily assessments and long-term follow-up. Daily blood samples allow in depth molecular-genetic characterization of patients. We established a well-organized workflow for sample logistics and a comprehensive data management system to collect and manage data from more than 50 study centers in Germany and Austria. Samples are stored in a central biobank and clinical data are stored in a central data base which also integrates all data from molecular assessments. Discussion: With the PROGRESS study, we established a comprehensive data base of high quality clinical and molecular data allowing investigation of pressing research questions regarding CAP. In-depth molecular characterization will contribute to the discovery of disease mechanisms and establishment of diagnostic and predictive biomarkers. A strength of PROGRESS is the focus on younger patients with low burden of co-morbidities, allowing a more direct look at host biology with less confounding. As a resulting limitation, insights from PROGRESS will require validation in representative patient cohorts to assess clinical utility. Trial registration: The PROGRESS study was retrospectively registered on May 24th, 2016 with ClinicalTrials.gov: NCT0278201