julilili42/papers huggingface dataset:
Company Cost of Capital and Leverage: A Simplified Textbook Relationship Revisited
2023-04-04

Abstract In this paper, we revisit a frequently employed simplification within the WACC approach that company cost of capital <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:msub> <mml:mi>k</mml:mi> <mml:mi>V</mml:mi> </mml:msub> </mml:mrow> </mml:math> is supposed to be invariant to the debt ratio and therefore equal to the unlevered cost <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:msub> <mml:mi>k</mml:mi> <mml:mi>U</mml:mi> </mml:msub> </mml:mrow> </mml:math> . Even though we know from Miles and Ezzell (1980) that <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:msub> <mml:mi>k</mml:mi> <mml:mi>V</mml:mi> </mml:msub> </mml:mrow> </mml:math> formally differs from <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:msub> <mml:mi>k</mml:mi> <mml:mi>U</mml:mi> </mml:msub> </mml:mrow> </mml:math> , treating both costs as equal strongly facilitates the practical firm valuation e.g. when companies strategically change their target debt ratios to a significantly different magnitude after a transaction. We provide both a theoretical model and an empirical analysis using 29 firms of the German stock market to quantify the economic significance between the company cost of a levered and an otherwise identical but unlevered firm. In particular, we can numerically support the usual simplification in the absence of default risk. In case that firms are default-risky, however, empirical findings indicate a clear difference between these costs equal to 1.88 percentage points on average even for moderate assumed bankruptcy costs which translates to a company mispricing of nearly 100%. As a result, the company cost of capital does practically not depend on the debt ratio if the firm is not subject to default risk or if bankruptcy costs are negligible. Otherwise, it does and a negligence of this relationship can cause significant mispricings.
Quasi-deuterons in light nuclei
2023-04-04

Abstract The role of pairing correlations for nucleon pairs with isospin T = 1 and T = 0 is investigated for ground-states of nuclei in the mass region 12 ≤ A ≤ 42. For that purpose, the two-nucleon densities resulting from nuclear shell-model calculations in one and two major shells are analyzed. Various tools are applied in this analysis including the sensitivity of correlation effects on components of the NN interaction. Significant effects on the resulting energies are observed due to the formation of T = 0 pairs. The formation of quasi-deuterons is maximal for symmetric nuclei with N = Z . The formation of T = 0 pairs is less sensitive to the density of single-particle states close to the Fermi energy than the T = 1 pairing. Therefore the correlations in T = 0 pairs are relevant also for excitations across shell closures. This robustness also explains why T = 0 pairing does not lead to such clear evidence in comparing energies of neighbored nuclei as the ‘odd–even mass staggering’ due to the formation of T = 1 pairing.
Abstract 187: Let’s get physiological! Impact of media conditions on drug response to targeted therapies in CRC organoids
2023-04-04

Abstract Physiologically relevant in vitro tumor models are crucial in any research setting from drug development to individualized treatment predictions. Patient-derived 3D cell culture models (PD3D®) are validated cancer models which recapitulate the biology of the donor tissue from genotype to phenotype. A multitude of PD3D® replicates can be generated and these are suitable for high-throughput-screening. However, the influence of media conditions on specific drug sensitivity profiles widely remains elusive and thus the predictive value of screenings is obscured. Here we have investigated pathway activities in dependence of different media compositions and mapped out differences in response to targeted therapies and distinct growth media. We assessed the response of PD3D® models derived from colorectal carcinoma (CRC) patients towards two targeted drugs aiming at different levels of the EGFR/Ras/Raf/Mek/Erk axis in defined, serum-free culture media. One media composition contained growth factors in concentration prevalently used in published cell culture protocols, while the other composition is geared to better match physiological levels of relevant supplements. We observed a significant impact of media conditions on sensitivity towards targeted cancer drugs. However, these differences were as individual as the models and the sensitivity against the treatment. To uncover the underlying mechanisms in the observed discrepancy we used DigiWest - a targeted proteomics technology - to assess pathways activity in the different models. We applied a panel of over 250 (phospho-)antibodies against proteins in the MAPK/ERK/RAS, PI3K/AKT and mTOR pathways as well as cell cycle and proliferation. Using functional pathway analysis, we mapped out the difference in response to targeted therapies and distinct growth media. In conclusion, media composition has great impact on the response to targeted drugs in vitro and therefore needs to be harmonized to ensure relevant results. Combination of PD3D® models and DigiWest functional pathway analysis represents a powerful tool to identify the molecular mechanisms underlying differential drug response. Further development of this collaborative approach will lead to a better understanding of the drug resistance or sensitivity and potentially even identification of signatures related to them. Citation Format: Jürgen Loskutov, Gerrit Erdmann, Anja Arndt, Quirin Graf Adelmann, Przemyslaw Dudys, Marie Flechner, Madeleine Nadolny, Katja Osman, Ulrike Pfohl, Christoph Reinhard, Markus Templin, Katja Uhlig, Lena Wedeken, Christian Regenbrecht. Let’s get physiological! Impact of media conditions on drug response to targeted therapies in CRC organoids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 187.
Cross-species communication viaagrcontrols phage susceptibility inStaphylococcus aureus
2023-04-04

Abstract Bacteria and their viruses (phages) use quorum sensing (QS) systems to coordinate group behavior. In Staphylococcus aureus , QS plays a critical role in the transition from colonization to infection and involves the accumulation of auto-inducing peptides (AIPs). Humans and animals are also colonized by non-aureus staphylococci (NAS) that produce AIPs, many of which inhibit S. aureus QS. We found that QS induction is necessary for S. aureus susceptibility to the lytic phage, Stab20 and that in mixed communities with NAS producing inhibitory AIPs, S. aureus is protected from phage infection. The primary phage receptors in S. aureus are wall teichoic acids (WTA) substituted with α- and/or β-linked N- acetylglucosamine (GlcNAc). We show that QS induction reduces α-GlcNAc substitutions and enables Stab20 infection through binding to β-glycosylated WTA. However, in the presence of inhibitory AIPs or during co-culture with NAS, QS induction and Stab20 infection are impeded. Our results highlight how cross-species communication can significantly impact bacterial susceptibility to phages and may explain occasional failures observed when phages are used as antimicrobials in for example phage therapy.
Integration of Extracellular Matrices into Organ‐on‐Chip Systems
2023-04-05

Abstract The extracellular matrix (ECM) is a complex, dynamic network present within all tissues and organs that not only acts as a mechanical support and anchorage point but can also direct fundamental cell behavior, function, and characteristics. Although the importance of the ECM is well established, the integration of well‐controlled ECMs into Organ‐on‐Chip (OoC) platforms remains challenging and the methods to modulate and assess ECM properties on OoCs remain underdeveloped. In this review, current state‐of‐the‐art design and assessment of in vitro ECM environments is discussed with a focus on their integration into OoCs. Among other things, synthetic and natural hydrogels, as well as polydimethylsiloxane (PDMS) used as substrates, coatings, or cell culture membranes are reviewed in terms of their ability to mimic the native ECM and their accessibility for characterization. The intricate interplay among materials, OoC architecture, and ECM characterization is critically discussed as it significantly complicates the design of ECM‐related studies, comparability between works, and reproducibility that can be achieved across research laboratories. Improving the biomimetic nature of OoCs by integrating properly considered ECMs would contribute to their further adoption as replacements for animal models, and precisely tailored ECM properties would promote the use of OoCs in mechanobiology.
Analyses of Spatial Correlation and Coherence in ABL Flow with a Fleet of UAS
2023-04-05

Abstract The spatial structures of turbulent flow in the atmospheric boundary layer (ABL) are complex and diverse. Multi-point spatial correlation measurements can help improve our understanding of these structures and their statistics. In this context, we investigate Taylor’s hypothesis and the statistics of spatial structures on the microscale. For the first time, simultaneous horizontally distributed wind measurements with a fleet of 20 quadrotor UAS (unmanned aerial systems) are realized. The measurements were taken at different heights and under different atmospheric conditions at the boundary layer field site in Falkenberg of the German Meteorological Service (DWD). A horizontal flight pattern has been specifically developed, consisting of measurements distributed along and lateral to the mean flow direction with separation distances of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mn>5</mml:mn> <mml:mo>...</mml:mo> <mml:mn>205</mml:mn> </mml:mrow> </mml:math> m. The validity of Taylor’s hypothesis is studied by examining the cross-correlations of longitudinally distributed UAS and comparing them with the autocorrelations of single UAS. To assess the similarity of flow structures on different scales, the lateral and longitudinal coherence of the streamwise velocity component is examined. Two modeling approaches for the decay of coherence are compared. The experimental results are in good agreement with the model approaches for neutral atmospheric conditions, whereas in stable and convective ABL, the exponential approaches are not unconditionally valid. The validation results and the agreement with the literature on coherence in the ABL underline the potential of the UAS fleet for the purpose of spatial turbulence measurements.
Zinc enrichment and isotopic fractionation in a marine habitat of the c. 2.1 Ga Francevillian Group: A signature of zinc utilization by eukaryotes?
2023-04-05

Constraining the timing of eukaryogenesis and the divergence of eukaryotic clades is a major challenge in evolutionary biology. Here, we present trace metal concentration and zinc isotope data for c. 2.1 billion-year-old Francevillian Group pyritized structures, previously described as putative remnants of the first colonial multicellular organisms, and their host black shales. Relative to the host rocks, pyritized structures are strongly enriched in zinc, cobalt and nickel, by at least one order of magnitude, with markedly lighter zinc isotope compositions. A metabolic demand for high concentrations of aqueous zinc, cobalt, and nickel combined with preferential uptake of lighter zinc isotopes may indicate metalloenzyme utilization by eukaryotes in marine habitats c. 2.1 billion years ago. Once confirmed, this would provide a critical calibration point for eukaryogenesis, suggesting that this major evolutionary innovation may have happened contemporaneously with elevated atmospheric oxygen levels during the latter part of the Great Oxidation Event, some 400 million years earlier than is currently widely accepted.
Profile of the multicenter cohort of the German Cancer Consortium’s Clinical Communication Platform
2023-04-05

Abstract Treatment concepts in oncology are becoming increasingly personalized and diverse. Successively, changes in standards of care mandate continuous monitoring of patient pathways and clinical outcomes based on large, representative real-world data. The German Cancer Consortium’s (DKTK) Clinical Communication Platform (CCP) provides such opportunity. Connecting fourteen university hospital-based cancer centers, the CCP relies on a federated IT-infrastructure sourcing data from facility-based cancer registry units and biobanks. Federated analyses resulted in a cohort of 600,915 patients, out of which 232,991 were incident since 2013 and for which a comprehensive documentation is available. Next to demographic data (i.e., age at diagnosis: 2.0% 0–20 years, 8.3% 21–40 years, 30.9% 41–60 years, 50.1% 61–80 years, 8.8% 81+ years; and gender: 45.2% female, 54.7% male, 0.1% other) and diagnoses (five most frequent tumor origins: 22,523 prostate, 18,409 breast, 15,575 lung, 13,964 skin/malignant melanoma, 9005 brain), the cohort dataset contains information about therapeutic interventions and response assessments and is connected to 287,883 liquid and tissue biosamples. Focusing on diagnoses and therapy-sequences, showcase analyses of diagnosis-specific sub-cohorts (pancreas, larynx, kidney, thyroid gland) demonstrate the analytical opportunities offered by the cohort’s data. Due to its data granularity and size, the cohort is a potential catalyst for translational cancer research. It provides rapid access to comprehensive patient groups and may improve the understanding of the clinical course of various (even rare) malignancies. Therefore, the cohort may serve as a decisions-making tool for clinical trial design and contributes to the evaluation of scientific findings under real-world conditions.
The Mannheimer Craving Scale (MaCS): Psychometric properties in a non-clinical sample and development of cut-off scores
2023-04-05

This manuscript was submitted to and rejected by five different scientific journals in the years 2011 and 2012. After the last journal rejected it after the second revision, I didn't submit it anywhere else. So, as it will never be published in a scientifc journal, I guess it can't be called a "preprint" anymore but is now an "unpublished manuscript" (although this also seems inaccurate as it is published on ResearchGate and PsyArxiv). Maybe some readers who use the Mannheimer Craving Scale will still find it interesting.
Building pangenome graphs
2023-04-06

Abstract Pangenome graphs can represent all variation between multiple reference genomes, but current approaches to build them exclude complex sequences or are based upon a single reference. In response, we developed the PanGenome Graph Builder (PGGB), a pipeline for constructing pangenome graphs without bias or exclusion. PGGB uses all-to-all alignments to build a variation graph in which we can identify variation, measure conservation, detect recombination events, and infer phylogenetic relationships.
Glucocerebrosidase is imported into mitochondria and preserves complex I integrity and energy metabolism
2023-04-06

Abstract Mutations in GBA1 , the gene encoding the lysosomal enzyme β-glucocerebrosidase (GCase), which cause Gaucher’s disease, are the most frequent genetic risk factor for Parkinson’s disease (PD). Here, we employ global proteomic and single-cell genomic approaches in stable cell lines as well as induced pluripotent stem cell (iPSC)-derived neurons and midbrain organoids to dissect the mechanisms underlying GCase-related neurodegeneration. We demonstrate that GCase can be imported from the cytosol into the mitochondria via recognition of internal mitochondrial targeting sequence-like signals. In mitochondria, GCase promotes the maintenance of mitochondrial complex I (CI) integrity and function. Furthermore, GCase interacts with the mitochondrial quality control proteins HSP60 and LONP1. Disease-associated mutations impair CI stability and function and enhance the interaction with the mitochondrial quality control machinery. These findings reveal a mitochondrial role of GCase and suggest that defective CI activity and energy metabolism may drive the pathogenesis of GCase-linked neurodegeneration.
Detection of extended γ-ray emission around the Geminga pulsar with H.E.S.S.
2023-04-06

Geminga is an enigmatic radio-quiet γ -ray pulsar located at a mere 250 pc distance from Earth. Extended very-high-energy γ -ray emission around the pulsar was discovered by Milagro and later confirmed by HAWC, which are both water Cherenkov detector-based experiments. However, evidence for the Geminga pulsar wind nebula in gamma rays has long evaded detection by imaging atmospheric Cherenkov telescopes (IACTs) despite targeted observations. The detection of γ -ray emission on angular scales ≳2o poses a considerable challenge for the background estimation in IACT data analysis. With recent developments in understanding the complementary background estimation techniques of water Cherenkov and atmospheric Cherenkov instruments, the H.E.S.S. IACT array can now confirm the detection of highly extended γ -ray emission around the Geminga pulsar with a radius of at least 3o in the energy range 0.5–40 TeV. We find no indications for statistically significant asymmetries or energy-dependent morphology. A flux normalisation of (2.8 ± 0.7) × 10 −12 cm −2 s −1 TeV −1 at 1 TeV is obtained within a 1o radius region around the pulsar. To investigate the particle transport within the halo of energetic leptons around the pulsar, we fitted an electron diffusion model to the data. The normalisation of the diffusion coefficient obtained of D 0 = 7.6 −1.2 +1.5 × 10 27 cm 2 s −1 , at an electron energy of 100 TeV, is compatible with values previously reported for the pulsar halo around Geminga, which is considerably below the Galactic average.
In-depth optical characterization of spectacle lenses for myopia progression management
2023-04-06

Myopia is one of the most common ocular disorders worldwide and the leading cause of visual impairment in children. The elongation of axial length in the eyes with medium and high levels of myopia can increase the risk of severe ocular pathologies that potentially lead to irreversible blindness. In recent decades, spectacle lenses have been designed, manufactured, and clinically tested to treat myopia progression and abnormal ocular growth in children. However, the optical characterization of those lenses—with and without considering the optics of myopic eyes—has not yet been comprehensively evaluated and compared. Therefore, in this paper, we quantify and compare the focusing and scattering properties of a single vision (SV) lens with two types of spectacle lenses for myopia progression management: defocus incorporated multiple segments (DIMS), and diffusion-optical technology (DOT). To investigate the focusing properties across the eccentricity of the lenses, we have developed an instrument based on spatial light modulation technology that reproduces myopic eyes’ foveal and peripheral aberrations. Our characterization showed an increased contrast and sharpness of images through the DIMS lens at the peripheral retina when inducing myopic defocus with respect to the SV and DOT lenses. On the other hand, the contrast reduction by the DOT lens strongly depends on the luminance at the pupil. The understanding of the imaging properties of the lenses achieved through our results might help optimize future spectacles designs for myopia progression management.
Pulse profile modelling of thermonuclear burst oscillations − I. The effect of neglecting variability
2023-04-06

ABSTRACT We study the effects of the time-variable properties of thermonuclear X-ray bursts on modelling their millisecond-period burst oscillations. We apply the pulse profile modelling technique that is being used in the analysis of rotation-powered millisecond pulsars by the Neutron Star Interior Composition Explorer to infer masses, radii, and geometric parameters of neutron stars. By simulating and analysing a large set of models, we show that overlooking burst time-scale variability in temperatures and sizes of the hot emitting regions can result in substantial bias in the inferred mass and radius. To adequately infer neutron star properties, it is essential to develop a model for the time-variable properties or invest a substantial amount of computational time in segmenting the data into non-varying pieces. We discuss prospects for constraints from proposed future X-ray telescopes.
What Would an Alien Amino Acid Alphabet Look Like and Why?
2023-04-06

Life on Earth builds genetically encoded proteins by using a standard alphabet of just 20 L-α-amino acids, although many others were available to life's origins and early evolution. To better understand the causes of this foundational evolutionary outcome, we extend previous analyses which have identified a highly unusual distribution of biophysical properties within the set used by life. Specifically, we use a heuristic search algorithm to identify other sets of amino acids, from a library of plausible alternatives, that emulate life's signature. We find that a subset of amino acids seems predisposed to forming such sets. We present other examples of such alphabets under various assumptions, along with analysis and reasoning about why each might be simplistic. We do so to introduce the central, open question that remains: while fundamental biophysics related to protein folding can potentially reduce a library of 10<sup>54</sup> possible amino acid alphabets by 7 orders of magnitude, the framework of assumptions that does so leaves a further 10<sup>45</sup> possibilities. It is therefore tempting to ask what additional assumptions can further reduce these 45 orders of magnitude? We thus conclude with a focus on library and alphabet construction as a useful target for subsequent research that may help future science speak with more confidence about what an alien amino acid alphabet would look like and why.
Fluid Intelligence Is (Much) More than Working Memory Capacity: An Experimental Analysis
2023-04-06

Empirical evidence suggests a great positive association between measures of fluid intelligence and working memory capacity, which implied to some researchers that fluid intelligence is little more than working memory. Because this conclusion is mostly based on correlation analysis, a causal relationship between fluid intelligence and working memory has not yet been established. The aim of the present study was therefore to provide an experimental analysis of this relationship. In a first study, 60 participants worked on items of the Advanced Progressive Matrices (APM) while simultaneously engaging in one of four secondary tasks to load specific components of the working memory system. There was a diminishing effect of loading the central executive on the APM performance, which could explain 15% of the variance in the APM score. In a second study, we used the same experimental manipulations but replaced the dependent variable with complex working memory span tasks from three different domains. There was also a diminishing effect of the experimental manipulation on span task performance, which could now explain 40% of the variance. These findings suggest a causal effect of working memory functioning on fluid intelligence test performance, but they also imply that factors other than working memory functioning must contribute to fluid intelligence.