Hydrogen Spectroscopy with a Lamb-shift Polarimeter - An Alternative Approach Towards Anti-Hydrogen Spectroscopy Experiments

A Lamb-shift polarimeter, which has been built for a fast determination of the polarization of protons and deuterons of an atomic-beam source and which is frequently used in the ANKE experiment at COSY-J\"ulich, is shown to be an excellent device for atomic-spectroscopy measurements of metastable hydrogen isotopes. It is demonstrated that magnetic and electric dipole transitions in hydrogen can be measured as a function of the external magnetic field, giving access to the full Breit-Rabi diagram for the $2^2S_{1/2}$ and the $2^2P_{1/2}$ states. This will allow the study of hyperfine structure, $g$ factors and the classical Lamb shift. Although the data are not yet competitive with state-of-the-art measurements, the potential of the method is enormous, including a possible application to anti-hydrogen spectroscopy.Comment: 6 pages, 7 figures, accepted by European Physical Journal

Coevolutionary Landscape Inference and the Context-Dependence of Mutations in Beta-Lactamase TEM-1

The quantitative characterization of mutational landscapes is a task of outstanding importance in evolutionary and medical biology: It is, for example, of central importance for our understanding of the phenotypic effect of mutations related to disease and antibiotic drug resistance. Here we develop a novel inference scheme for mutational landscapes, which is based on the statistical analysis of large alignments of homologs of the protein of interest. Our method is able to capture epistatic couplings between residues, and therefore to assess the dependence of mutational effects on the sequence context where they appear. Compared with recent large-scale mutagenesis data of the beta-lactamase TEM-1, a protein providing resistance against beta-lactam antibiotics, our method leads to an increase of about 40% in explicative power as compared with approaches neglecting epistasis. We find that the informative sequence context extends to residues at native distances of about 20 Å from the mutated site, reaching thus far beyond residues in direct physical contact

Development of a scoring function for comparing simulated and experimental tumor spheroids

Progress continues in the field of cancer biology, yet much remains to be unveiled regarding the mechanisms of cancer invasion. In particular, complex biophysical mechanisms enable a tumor to remodel the surrounding extracellular matrix (ECM), allowing cells to invade alone or collectively. Tumor spheroids cultured in collagen represent a simplified, reproducible 3D model system, which is sufficiently complex to recapitulate the evolving organization of cells and interaction with the ECM that occur during invasion. Recent experimental approaches enable high resolution imaging and quantification of the internal structure of invading tumor spheroids. Concurrently, computational modeling enables simulations of complex multicellular aggregates based on first principles. The comparison between real and simulated spheroids represents a way to fully exploit both data sources, but remains a challenge. We hypothesize that comparing any two spheroids requires first the extraction of basic features from the raw data, and second the definition of key metrics to match such features. Here, we present a novel method to compare spatial features of spheroids in 3D. To do so, we define and extract features from spheroid point cloud data, which we simulated using Cells in Silico (CiS), a high-performance framework for large-scale tissue modeling previously developed by us. We then define metrics to compare features between individual spheroids, and combine all metrics into an overall deviation score. Finally, we use our features to compare experimental data on invading spheroids in increasing collagen densities. We propose that our approach represents the basis for defining improved metrics to compare large 3D data sets. Moving forward, this approach will enable the detailed analysis of spheroids of any origin, one application of which is informing in silico spheroids based on their in vitro counterparts. This will enable both basic and applied researchers to close the loop between modeling and experiments in cancer research

Rising Up: Hierarchical Metal–Organic Frameworks in Experiments and Simulations

Controlled synthesis across several length scales, ranging from discrete molecular building blocks to size‐ and morphology‐controlled nanoparticles to 2D sheets and thin films and finally to 3D architectures, is an advanced and highly active research field within both the metal–organic framework (MOF) domain and the overall material science community. Along with synthetic progress, theoretical simulations of MOF structures and properties have shown tremendous progress in both accuracy and system size. Further advancements in the field of hierarchically structured MOF materials will allow the optimization of their performance; however, this optimization requires a deep understanding of the different synthesis and processing techniques and an enhanced implementation of material modeling. Such modeling approaches will allow us to select and synthesize the highest‐performing structures in a targeted rational manner. Here, recent progress in the synthesis of hierarchically structured MOFs and multiscale modeling and associated simulation techniques is presented, along with a brief overview of the challenges and future perspectives associated with a simulation‐based approach toward the development of advanced hierarchically structured MOF materials

Nuclear spins, magnetic moments and quadrupole moments of Cu isotopes from N = 28 to N = 46: probes for core polarization effects

Measurements of the ground-state nuclear spins, magnetic and quadrupole moments of the copper isotopes from 61Cu up to 75Cu are reported. The experiments were performed at the ISOLDE facility, using the technique of collinear laser spectroscopy. The trend in the magnetic moments between the N=28 and N=50 shell closures is reasonably reproduced by large-scale shell-model calculations starting from a 56Ni core. The quadrupole moments reveal a strong polarization of the underlying Ni core when the neutron shell is opened, which is however strongly reduced at N=40 due to the parity change between the $pf$ and $g$ orbits. No enhanced core polarization is seen beyond N=40. Deviations between measured and calculated moments are attributed to the softness of the 56Ni core and weakening of the Z=28 and N=28 shell gaps.Comment: 13 pagers, 19 figures, accepted by Physical Review

Structural analysis of a genetically encoded fret biosensor by SAXS and MD simulations

Inspired by the modular architecture of natural signaling proteins, ligand binding proteins are equipped with two fluorescent proteins (FPs) in order to obtain Förster resonance energy transfer (FRET)-based biosensors. Here, we investigated a glucose sensor where the donor and acceptor FPs were attached to a glucose binding protein using a variety of different linker sequences. For three resulting sensor constructs the corresponding glucose induced conformational changes were measured by small angle X-ray scattering (SAXS) and compared to recently published single molecule FRET results (Höfig et al., ACS Sensors, 2018). For one construct which exhibits a high change in energy transfer and a large change of the radius of gyration upon ligand binding, we performed coarse-grained molecular dynamics simulations for the ligand-free and the ligand-bound state. Our analysis indicates that a carefully designed attachment of the donor FP is crucial for the proper transfer of the glucose induced conformational change of the glucose binding protein into a well pronounced FRET signal change as measured in this sensor construct. Since the other FP (acceptor) does not experience such a glucose induced alteration, it becomes apparent that only one of the FPs needs to have a well-adjusted attachment to the glucose binding protein

Genome-Wide Location Analysis Reveals Distinct Transcriptional Circuitry by Paralogous Regulators Foxa1 and Foxa2

Gene duplication is a powerful driver of evolution. Newly duplicated genes acquire new roles that are relevant to fitness, or they will be lost over time. A potential path to functional relevance is mutation of the coding sequence leading to the acquisition of novel biochemical properties, as analyzed here for the highly homologous paralogs Foxa1 and Foxa2 transcriptional regulators. We determine by genome-wide location analysis (ChIP-Seq) that, although Foxa1 and Foxa2 share a large fraction of binding sites in the liver, each protein also occupies distinct regulatory elements in vivo. Foxa1-only sites are enriched for p53 binding sites and are frequently found near genes important to cell cycle regulation, while Foxa2-restricted sites show only a limited match to the forkhead consensus and are found in genes involved in steroid and lipid metabolism. Thus, Foxa1 and Foxa2, while redundant during development, have evolved divergent roles in the adult liver, ensuring the maintenance of both genes during evolution.Institute for Diabetes, Obesity and Metabolism. Diabetes Research Center (Functional Genomics Core P30-DK19525