Showing papers by "University of Cologne published in 2022"

The diversity of core–halo structure in the fuzzy dark matter model

Abstract: In the fuzzy dark matter (FDM) model, gravitationally collapsed objects always consist of a solitonic core located within a virialised halo. Although various numerical simulations have confirmed that the collapsed structure can be described by a cored NFW like density profile, there is still disagreement about the relation between the core mass and the halo mass. To fully understand this relation, we have assembled a large sample of cored haloes based on both idealised soliton mergers and cosmological simulations with various box sizes. We find that there exists a sizeable dispersion in the core-halo mass relation that increases with halo mass, indicating that the FDM model allows cores and haloes to coexist in diverse configurations. We provide a new empirical equation for a core halo mass relation with uncertainties that can encompass all previously found relations in the dispersion, and emphasise that any observational constraints on the particle mass using a tight one-to-one core-halo mass relation should suffer from an additional uncertainty on the order of 50 % for halo masses $ \ge 10^9 (8 \times 10^{-23} eV/ (mc^2))^{3/2} M_\odot$. We suggest that tidal stripping may be one of the effects contributing to the scatter in the relation.

Why electricity market models yield different results: Carbon pricing in a model-comparison experiment

Abstract: The European electricity industry, the dominant sector of the world's largest cap-and-trade scheme, is one of the most-studied examples of carbon pricing. In particular, numerical models are often used to study the uncertain future development of carbon prices and emissions. While parameter uncertainty is often addressed through sensitivity analyses, the potential uncertainty of the models themselves remains unclear from existing single-model studies. This study investigates such model-related uncertainty by running a structured model comparison experiment, which exposes five numerical power sector models to aligned input parameters—finding stark model differences. At a carbon price of 27 EUR/t in 2030, the models estimate that European power sector emissions will decrease by 36–57% when compared to 2016. Most of this variation can be explained by the extent to which models consider the market-driven decommissioning of coal- and lignite-fired power plants. Higher carbon prices of 57 and 87 EUR/t yield a stronger decrease in carbon emissions, by 45–75% and 52–80%, respectively. The lower end of these ranges can be attributed to the short-term fuel switch captured by dispatch-only models. The higher reductions correspond to models that additionally consider market-based investment in renewables. By further studying cross-model variation in the remaining emissions at high carbon prices, the representation of combined heat and power is identified as another crucial driver of differences across model results.

Sleep problems and their interaction with physical activity and fatigue in hematological cancer patients during onset of high dose chemotherapy.

Abstract: Sleep problems reported by hematological cancer patients are usually linked to higher levels of cancer-related fatigue. Although the awareness of sleep problems in solid cancer patients is rising, there has been less attention to the issue in hematological cancer patients. The present study assesses the differences in sleep by comparing physical activity and fatigue levels among hematological cancer patients during the onset of chemotherapy. Furthermore, it investigates the relationship between sleep, physical activity, and fatigue through mediation analysis. The recruited sample consists of 58 newly diagnosed hematological cancer patients (47.1 ± 15.4 yrs; 51.7% males). Subjects completed questionnaires assessing sleep (PSQI), physical activity (visual analogue scale), fatigue (MFI-20), anxiety, depression (HADS), and quality of life (EORTC QLQ-C30) within two weeks from starting treatment. The sample reported more sleep problems in comparison to the German population norm. The classification as good (ca 25%) or bad sleepers (ca 75%) showed less frequent physical activity (p = .04), higher fatigue (p = .032), anxiety (p = .003), depression (p = .011) and pain (p = .011) in bad sleepers. The mediation analysis revealed significant indirect effects of sleep on fatigue through physical activity habits. This study highlights the combined action of sleep problems and physical activity on fatigue during the onset of induction chemotherapy. These two parameters could represent meaningful intervention targets to improve a patient’s status during chemotherapy. The study was registered on the WHO trial register (DRKS00007824).

Stronger together for in-cell translation: natural and unnatural base modified mRNA

Abstract: The preparation of highly modified mRNAs and visualization of their cellular distribution are challenging. We report in-cell application of in vitro transcribed mRNA containing natural base modifications and site-specifically introduced artificial nucleotides. Click chemistry on mRNA allows visualization in cells with excellent signal intensities. While non-specific introduction of reporter groups often leads to loss in mRNA functionality, we combined the benefits from site-specificity in the 3'-UTR incorporated unnatural nucleotides with the improved translation efficiency of the natural base modifications Ψ and 5mC. A series of experiments is described to observe, quantify and verify mRNA functionality. This approach represents a new way to visualize mRNA delivery into cells and monitor its spread on a cellular level and translation efficiency. We observed increased protein expression from this twofold chemically modified, artificial mRNA counterbalancing a reduced transfection rate. This synergetic effect can be exploited as a powerful tool for future research on mRNA therapeutics.

Bismuth-based halide perovskite and perovskite-inspired light absorbing materials for photovoltaics

Abstract: The efficiency of organic-inorganic hybrid lead halide perovskite solar cells (PSCs) has increased over 25% within a frame of ten years, which is phenomenal and indicative of the promising potential of perovskite materials in impacting the next generation solar cells. Despite high technology readiness of perovskite solar cells, the presence of lead has raised concerns about the adverse effect of lead on human health and the environment that may slow down or inhibit the commercialization of perovskite solar cells. Thus, there is a dire need to identify materials with lower toxicity profile and comparable optoelectronic properties in regard to lead-halide perovskites. In comparison to tin-, germanium-, and copper-based PSCs, which suffer from stability issues under ambient operation, bismuth-based perovskite and perovskite-inspired materials have gained attention because of their enhanced stability in ambient atmospheric conditions. In this topical review, we initially discuss the background of lead and various lead-free perovskite materials and further discuss the fundamental aspects of various bismuth-based perovskite and perovskite-inspired materials having a chemical formula of A3Bi2X9, A2B'BiX6, B'aBibXa+3b (A = Cs+, MA+ and bulky organic ligands; B' = Ag+, Cu+; X = I–, Cl–, Br–) and bismuth triiodide (BiI3) semiconducting material particularly focusing on their structure, optoelectronic properties and the influence of compositional variation on the photovoltaic device performance and stability.

The who’s who of a hydrogen market ramp-up: A stakeholder analysis for Germany

Abstract: The interest in low-carbon hydrogen technologies is growing fast in politics and the economy. The ramp-up of a hydrogen market is a critical phase, which requires the engagement and coordination of many heterogeneous stakeholders. A better understanding of who these stakeholders are and what relationships, chances, and risks they perceive is crucial to guide a hydrogen market ramp-up. This paper conducts a stakeholder analysis for Germany with a focus on the market ramp-up period. Interviews with 36 hydrogen experts, literature, and stakeholders from 78 real-world hydrogen research and demonstration projects are analysed with qualitative content analysis and social network analysis. In total, 49 stakeholder groups are identified and defined accordingly. The results indicate that established stakeholders’ roles will significantly change in a future hydrogen market. Risks range from economic and supply chain risks to impacts on international policy. Chances are found along economic, ecological, and political dimensions. Political intervention during the market ramp-up should mostly focus on the economic gap between low-carbon hydrogen and fossil alternatives and on prioritising the allocation of scarce hydrogen supply on heterogeneous demand. Simultaneously, a long-term strategy should be envisaged to guarantee a competitive and non-discriminatory hydrogen market in the future.

Mitochondrial membrane proteins and VPS35 orchestrate selective removal of mtDNA

Abstract: Abstract Understanding the mechanisms governing selective turnover of mutation-bearing mtDNA is fundamental to design therapeutic strategies against mtDNA diseases. Here, we show that specific mtDNA damage leads to an exacerbated mtDNA turnover, independent of canonical macroautophagy, but relying on lysosomal function and ATG5. Using proximity labeling and Twinkle as a nucleoid marker, we demonstrate that mtDNA damage induces membrane remodeling and endosomal recruitment in close proximity to mitochondrial nucleoid sub-compartments. Targeting of mitochondrial nucleoids is controlled by the ATAD3-SAMM50 axis, which is disrupted upon mtDNA damage. SAMM50 acts as a gatekeeper, influencing BAK clustering, controlling nucleoid release and facilitating transfer to endosomes. Here, VPS35 mediates maturation of early endosomes to late autophagy vesicles where degradation occurs. In addition, using a mouse model where mtDNA alterations cause impairment of muscle regeneration, we show that stimulation of lysosomal activity by rapamycin, selectively removes mtDNA deletions without affecting mtDNA copy number, ameliorating mitochondrial dysfunction. Taken together, our data demonstrates that upon mtDNA damage, mitochondrial nucleoids are eliminated outside the mitochondrial network through an endosomal-mitophagy pathway. With these results, we unveil the molecular players of a complex mechanism with multiple potential benefits to understand mtDNA related diseases, inherited, acquired or due to normal ageing.

Early Tracheostomy Is Associated With Shorter Ventilation Time and Duration of ICU Stay in Patients With Myasthenic Crisis-A Multicenter Analysis.

Abstract: Background:Myasthenic crisis (MC) requiring mechanical ventilation (MV) is a rare and serious complication of myasthenia gravis. Here we analyzed the frequency of performed tracheostomies, risk fac...

Local Rather than Global H3K27me3 Dynamics Are Associated with Differential Gene Expression in Verticillium dahliae

Abstract: Differential growth conditions typically trigger global transcriptional responses in filamentous fungi. Such fungal responses to environmental cues involve epigenetic regulation, including chemical histone modifications. It has been proposed that conditionally expressed genes, such as those that encode secondary metabolites but also effectors in pathogenic species, are often associated with a specific histone modification, lysine27 methylation of H3 (H3K27me3). However, thus far, no analyses on the global H3K27me3 profiles have been reported under differential growth conditions in order to assess if H3K27me3 dynamics govern differential transcription. Using chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing data from the plant-pathogenic fungus Verticillium dahliae grown in three in vitro cultivation media, we now show that a substantial number of the identified H3K27me3 domains globally display stable profiles among these growth conditions. However, we observe local quantitative differences in H3K27me3 ChIP-seq signals that are associated with a subset of differentially transcribed genes between media. Comparing the in vitro results to expression during plant infection suggests that in planta-induced genes may require chromatin remodeling to achieve expression. Overall, our results demonstrate that some loci display H3K27me3 dynamics associated with concomitant transcriptional variation, but many differentially expressed genes are associated with stable H3K27me3 domains. Thus, we conclude that while H3K27me3 is required for transcriptional repression, it does not appear that transcriptional activation requires the global erasure of H3K27me3. We propose that the H3K27me3 domains that do not undergo dynamic methylation may contribute to transcription through other mechanisms or may serve additional genomic regulatory functions. IMPORTANCE In many organisms, including filamentous fungi, epigenetic mechanisms that involve chemical and physical modifications of DNA without changing the genetic sequence have been implicated in transcriptional responses upon developmental or environmental cues. In fungi, facultative heterochromatin that can decondense to allow transcription in response to developmental changes or environmental stimuli is characterized by the trimethylation of lysine 27 on histone H3 (H3K27me3), and H3K27me3 has been implicated in transcriptional regulation, although the precise mechanisms and functions remain enigmatic. Based on ChIP and RNA sequencing data, we show for the soilborne broad-host-range vascular wilt plant-pathogenic fungus Verticillium dahliae that although some loci display H3K27me3 dynamics that can contribute to transcriptional variation, other loci do not show such a dependence. Thus, although we recognize that H3K27me3 is required for transcriptional repression, we also conclude that this mark is not a conditionally responsive global regulator of differential transcription upon responses to environmental cues.

Analytic Criminology: Mechanisms and Methods in the Explanation of Crime and its Causes

Abstract: Criminology is a smorgasbord of disparate theory and poorly integrated research findings. Theories tend to focus either on people's crime propensity or the criminogenic inducements of environments;...

Ganymede MHD Model: Magnetospheric Context for Juno's PJ34 Flyby

Abstract: On 7 June 2021 the Juno spacecraft visited Ganymede and provided the first in situ observations since Galileo's last flyby in 2000. The measurements obtained along a one-dimensional trajectory can be brought into global context with the help of three-dimensional magnetospheric models. Here we apply the magnetohydrodynamic model of Duling et al. (2014, https://doi.org/10.1002/2013ja019554) to conditions during the Juno flyby. In addition to the global distribution of plasma variables we provide mapping of Juno's position along magnetic field lines, Juno's distance from closed field lines and detailed information about the magnetic field's topology. We find that Juno did not enter the closed field line region and that the boundary between open and closed field lines on the surface matches the poleward edges of the observed auroral ovals. To estimate the sensitivity of the model results, we carry out a parameter study with different upstream plasma conditions and other model parameters.

Giant magnetochiral anisotropy from quantum-confined surface states of topological insulator nanowires

Abstract: Wireless technology relies on the conversion of alternating electromagnetic fields to direct currents, a process known as rectification. While rectifiers are normally based on semiconductor diodes, quantum mechanical non-reciprocal transport effects that enable highly controllable rectification have recently been discovered. One such effect is magnetochiral anisotropy (MCA), where the resistance of a material or a device depends on both the direction of current flow and an applied magnetic field. However, the size of rectification possible due to MCA is usually extremely small, because MCA relies on inversion symmetry breaking leading to the manifestation of spin-orbit coupling, which is a relativistic effect. In typical materials the rectification coefficient $\gamma$ due to MCA is usually $|\gamma| \lesssim 1$ ${\rm A^{-1} T^{-1}}$ and the maximum values reported so far are $|\gamma| \sim 100$ ${\rm A^{-1} T^{-1}}$ in carbon nanotubes and ZrTe$_5$. Here, to overcome this limitation, we artificially break inversion symmetry via an applied gate voltage in thin topological insulator (TI) nanowire heterostructures and theoretically predict that such a symmetry breaking can lead to a giant MCA effect. Our prediction is confirmed via experiments on thin bulk-insulating (Bi$_{1-x}$Sb$_{x}$)$_2$Te$_3$ TI nanowires, in which we observe an MCA consistent with theory and $|\gamma| \sim 100000$ ${\rm A^{-1} T^{-1}}$, the largest ever reported MCA rectification coefficient in a normal conductor.

Liquid-Liver Phantom

Abstract: Objectives Tissue stiffness can guide medical diagnoses and is exploited as an imaging contrast in elastography. However, different elastography devices show different liver stiffness values in the same subject, hindering comparison of values and establishment of system-independent thresholds for disease detection. There is a need for standardized phantoms that specifically address the viscosity-related dispersion of stiffness over frequency. To improve standardization of clinical elastography across devices and platforms including ultrasound and magnetic resonance imaging (MRI), a comprehensively characterized phantom is introduced that mimics the dispersion of stiffness of the human liver and can be generated reproducibly. Materials and Methods The phantom was made of linear polymerized polyacrylamide (PAAm) calibrated to the viscoelastic properties of healthy human liver in vivo as reported in the literature. Stiffness dispersion was analyzed using the 2-parameter springpot model fitted to the dispersion of shear wave speed of PAAm, which was measured by shear rheometry, ultrasound-based time-harmonic elastography, clinical magnetic resonance elastography (MRE), and tabletop MRE in the frequency range of 5 to 3000 Hz. Imaging parameters for ultrasound and MRI, reproducibility, aging behavior, and temperature dependency were assessed. In addition, the frequency bandwidth of shear wave speed of clinical elastography methods (Aplio i900, Canon; Acuson Sequoia, Siemens; FibroScan, EchoSense) was characterized. Results Within the entire frequency range analyzed in this study, the PAAm phantom reproduced well the stiffness dispersion of human liver in vivo despite its fluid properties under static loading (springpot stiffness parameter, 2.14 [95% confidence interval, 2.08–2.19] kPa; springpot powerlaw exponent, 0.367 [95% confidence interval, 0.362–0.373]). Imaging parameters were close to those of liver in vivo with only slight variability in stiffness values of 0.5% (0.4%, 0.6%), 4.1% (3.9%, 4.5%), and −0.63% (−0.67%, −0.58%), respectively, between batches, over a 6-month period, and per °C increase in temperature. Conclusions The liquid-liver phantom has useful properties for standardization and development of liver elastography. First, it can be used across clinical and experimental elastography devices in ultrasound and MRI. Second, being a liquid, it can easily be adapted in size and shape to specific technical requirements, and by adding inclusions and scatterers. Finally, because the phantom is based on noncrosslinked linear PAAm constituents, it is easy to produce, indicating potential widespread use among researchers and vendors to standardize liver stiffness measurements.

Electrospun BiFeO ₃ Nanofibers for Vibrational Energy Harvesting Application

Abstract: Bismuth ferrite (BiFeO3, BFO) has found application in a wide range of fields owing to its fascinating multiferroic properties. Herein, the interplay between the piezoelectric properties and morphology of BFO nanostructures is exploited for vibrational energy harvesting application by tailoring BFO to a high aspect ratio and high surface area nanofiber morphology. This work demonstrates a facile pathway for the fabrication of high-performance flexible nanogenerators, based on BFO nanofibers, from a cost-effective and energy-efficient electrospinning technique. The X-ray diffraction data of calcined fibers confirm the formation of noncentrosymmetric crystalline perovskite phase. The morphological characterization by scanning electron microscopy shows a compact anisotropic nanofibrous morphology. For the fabrication of nanogenerators, BFO nanofibers are embedded in a piezoactive polymer matrix (polyvinylidenfluoride [PVDF]). As-fabricated BFO/PVDF composite nanogenerators produce a high peak-to-peak voltage output of 7.6 V, with an average output power density of 185 ± 106 nW cm−2 upon periodic application of force through finger knocking.

On the accuracy of H <scp>i</scp> observations in molecular clouds – More cold H <scp>i</scp> than thought?

Abstract: ABSTRACT We present a study of the cold atomic hydrogen (H i) content of molecular clouds simulated within the SILCC-Zoom project for solar neighbourhood conditions. We produce synthetic observations of H i at 21 cm, including H i self-absorption (HISA) and observational effects. We find that H i column densities, $N_{\rm H\, \small {\rm I}}$, of ≳1022 cm−2 are frequently reached in molecular clouds with H i temperatures as low as ∼10 K. Hence, HISA observations assuming a fixed H i temperature tend to underestimate the amount of cold H i in molecular clouds by a factor of 3–10 and produce an artificial upper limit of $N_{\rm H\, \small {\rm I}}$ around 1021 cm−2. We thus argue that the cold H i mass in molecular clouds could be a factor of a few higher than previously estimated. Also, $N_{\rm H\, \small {\rm I}}$ PDFs obtained from HISA observations might be subject to observational biases and should be considered with caution. The underestimation of cold H i in HISA observations is due to both the large H i temperature variations and the effect of noise in regions of high optical depth. We find optical depths of cold H i around 1–10, making optical depth corrections essential. We show that the high H i column densities (≳1022 cm−2) can in parts be attributed to the occurrence of up to 10 individual H i–H2 transitions along the line of sight. This is also reflected in the spectra, necessitating Gaussian decomposition algorithms for their in-depth analysis. However, also for a single H i–H2 transition, $N_{\rm H\, \small {\rm I}}$ frequently exceeds 1021 cm−2, challenging one-dimensional, semi-analytical models. This is due to non-equilibrium chemistry effects and the fact that H i–H2 transition regions usually do not possess a one-dimensional geometry. Finally, we show that the H i gas is moderately supersonic with Mach numbers of a few. The corresponding non-thermal velocity dispersion can be determined via HISA observations within a factor of ∼2.

A Standardized Investigational Ki-67 Immunohistochemistry Assay Used to Assess High-Risk Early Breast Cancer Patients in the monarchE Phase 3 Clinical Study Identifies a Population With Greater Risk of Disease Recurrence When Treated With Endocrine Therapy Alone

Abstract: The objectives were to develop a standardized Ki-67 immunohistochemistry (IHC) method for precise, robust, and reproducible assessment of patients with early breast cancer, and utilize this assay to evaluate patients participating in the monarchE study (NCT03155997). The Ki-67 assay was developed and validated for sensitivity, specificity, repeatability, precision, and robustness using a predefined ≥20% cutoff. Reproducibility studies (intersite and intrasite, interobserver and intraobserver) were conducted at 3 external laboratories using detailed scoring instructions designed for monarchE. Using the assay, patient tumors were classified as displaying high (≥20%) or low (<20%) Ki-67 expression; Kaplan-Meier methods evaluated 2-year invasive disease-free survival rates for these 2 groups among patients treated with endocrine therapy (ET) alone. All analytical validation and reproducibility studies achieved point estimates of >90% for negative, positive, and overall percent agreement. Intersite reproducibility produced point estimate values of 94.7%, 100.0%, and 97.3%. External interobserver reproducibility produced point estimate values of 98.9%, 97.8%, and 98.3%. Among 1954 patients receiving ET alone, 986 (50.5%) had high and 968 (49.5%) had low Ki-67 expression. Patients with high Ki-67 had a clinically meaningful increased risk of developing invasive disease within 2 years compared with those with low Ki-67 [2-y invasive disease-free survival rate: 86.1% (95% confidence interval: 83.1%-88.7%) vs. 92.0% (95% confidence interval: 89.7%-93.9%), respectively]. This standardized Ki-67 methodology resulted in high concordance across multiple laboratories, and its use in the monarchE study prospectively demonstrated the prognostic value of Ki-67 IHC in HR+, HER2- early breast cancer with high-risk clinicopathologic features.

Intron-mediated induction of phenotypic heterogeneity

Abstract: Abstract Intragenic regions that are removed during maturation of the RNA transcript—introns—are universally present in the nuclear genomes of eukaryotes 1 . The budding yeast, an otherwise intron-poor species, preserves two sets of ribosomal protein genes that differ primarily in their introns 2,3 . Although studies have shed light on the role of ribosomal protein introns under stress and starvation 4–6 , understanding the contribution of introns to ribosome regulation remains challenging. Here, by combining isogrowth profiling 7 with single-cell protein measurements 8 , we show that introns can mediate inducible phenotypic heterogeneity that confers a clear fitness advantage. Osmotic stress leads to bimodal expression of the small ribosomal subunit protein Rps22B, which is mediated by an intron in the 5′ untranslated region of its transcript. The two resulting yeast subpopulations differ in their ability to cope with starvation. Low levels of Rps22B protein result in prolonged survival under sustained starvation, whereas high levels of Rps22B enable cells to grow faster after transient starvation. Furthermore, yeasts growing at high concentrations of sugar, similar to those in ripe grapes, exhibit bimodal expression of Rps22B when approaching the stationary phase. Differential intron-mediated regulation of ribosomal protein genes thus provides a way to diversify the population when starvation threatens in natural environments. Our findings reveal a role for introns in inducing phenotypic heterogeneity in changing environments, and suggest that duplicated ribosomal protein genes in yeast contribute to resolving the evolutionary conflict between precise expression control and environmental responsiveness 9 .

Power spectrum for perturbations in an inflationary model for a closed universe

Abstract: We derive the power spectrum of primordial quantum fluctuations in an inflationary universe for curvature parameter ${\mathcal K}=1$. This is achieved through a Born--Oppenheimer type of approximation scheme from the Wheeler--DeWitt equation of canonical quantum gravity using gauge-invariant variables. Compared to the flat model, the closed model exhibits a deficit of power at large scales.