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In response to pathogen infection, gasdermin (GSDM) proteins form membrane pores that induce a host cell death process called pyroptosis1–3. Studies of human and mouse GSDM pores reveal the functions and architectures of 24–33 protomers assemblies4–9, but the mechanism and evolutionary origin of membrane targeting and GSDM pore formation remain unknown. Here we determine a structure of a bacterial GSDM (bGSDM) pore and define a conserved mechanism of pore assembly. Engineering a panel of bGSDMs for site-specific proteolytic activation, we demonstrate that diverse bGSDMs form distinct pore sizes that range from smaller mammalian-like assemblies to exceptionally large pores containing >50 protomers. We determine a 3.3 Å cryo-EM structure of a Vitiosangium bGSDM in an active slinky-like oligomeric conformation and analyze bGSDM pores in a native lipid environment to create an atomic-level model of a full 52-mer bGSDM pore. Combining our structural analysis with molecular dynamics simulations and cellular assays, we define a stepwise model of GSDM pore assembly and demonstrate that pore formation is driven by local unfolding of membrane-spanning β-strand regions and pre-insertion of a covalently bound palmitoyl into the target membrane. These results yield insights into the diversity of GSDM pores found in nature and the function of an ancient post-translational modification in enabling a programmed host cell death process.
In response to pathogen infection, gasdermin (GSDM) proteins form membrane pores that induce a host cell death process called pyroptosis1–3. Studies of human and mouse GSDM pores reveal the functions and architectures of 24–33 protomers assemblies4–9, but the mechanism and evolutionary origin of membrane targeting and GSDM pore formation remain unknown. Here we determine a structure of a bacterial GSDM (bGSDM) pore and define a conserved mechanism of pore assembly. Engineering a panel of bGSDMs for site-specific proteolytic activation, we demonstrate that diverse bGSDMs form distinct pore sizes that range from smaller mammalian-like assemblies to exceptionally large pores containing >50 protomers. We determine a 3.3 Å cryo-EM structure of a Vitiosangium bGSDM in an active slinky-like oligomeric conformation and analyze bGSDM pores in a native lipid environment to create an atomic-level model of a full 52-mer bGSDM pore. Combining our structural analysis with molecular dynamics simulations and cellular assays, our results support a stepwise model of GSDM pore assembly and suggest that a covalently bound palmitoyl can leave a hydrophobic sheath and insert into the membrane before formation of the membrane-spanning β-strand regions. These results reveal the diversity of GSDM pores found in nature and explain the function of an ancient post-translational modification in enabling programmed host cell death.
Background: Alternative splicing is a key mechanism in eukaryotic cells to increase the effective number of functionally distinct gene products. Using bulk RNA sequencing, splicing variation has been studied both across human tissues and in genetically diverse individuals. This has identified disease-relevant splicing events, as well as associations between splicing and genomic variations, including sequence composition and conservation. However, variability in splicing between single cells from the same tissue and its determinants remain poorly understood.
Results: We applied parallel DNA methylation and transcriptome sequencing to differentiating human induced pluripotent stem cells to characterize splicing variation (exon skipping) and its determinants. Our results shows that splicing rates in single cells can be accurately predicted based on sequence composition and other genomic features. We also identified a moderate but significant contribution from DNA methylation to splicing variation across cells. By combining sequence information and DNA methylation, we derived an accurate model (AUC=0.85) for predicting different splicing modes of individual cassette exons. These explain conventional inclusion and exclusion patterns, but also more subtle modes of cell-to-cell variation in splicing. Finally, we identified and characterized associations between DNA methylation and splicing changes during cell differentiation.
Conclusions: Our study yields new insights into alternative splicing at the single-cell level and reveals a previously underappreciated component of DNA methylation variation on splicing.
Background: Alternative splicing is a key regulatory mechanism in eukaryotic cells and increases the effective number of functionally distinct gene products. Using bulk RNA sequencing, splicing variation has been studied across human tissues and in genetically diverse populations. This has identified disease-relevant splicing events, as well as associations between splicing and genomic variations, including sequence composition and conservation. However, variability in splicing between single cells from the same tissue or cell type and its determinants remain poorly understood.
Results: We applied parallel DNA methylation and transcriptome sequencing to differentiating human induced pluripotent stem cells to characterize splicing variation (exon skipping) and its determinants. Our results shows that variation in single-cell splicing can be accurately predicted based on local sequence composition and genomic features. We observe moderate but consistent contributions from local DNA methylation profiles to splicing variation across cells. A combined model that is built based on sequence as well as DNA methylation information accurately predicts different splicing modes of individual cassette exons (AUC=0.85). These categories include the conventional inclusion and exclusion patterns, but also more subtle modes of cell-to-cell variation in splicing. Finally, we identified and characterized associations between DNA methylation and splicing changes during cell differentiation.
Conclusions: Our study yields new insights into alternative splicing at the single-cell level and reveals a previously underappreciated link between DNA methylation variation and splicing.
Background: Alternative splicing is a key regulatory mechanism in eukaryotic cells and increases the effective number of functionally distinct gene products. Using bulk RNA sequencing, splicing variation has been studied across human tissues and in genetically diverse populations. This has identified disease-relevant splicing events, as well as associations between splicing and genomic features, including sequence composition and conservation. However, variability in splicing between single cells from the same tissue or cell type and its determinants remains poorly understood.
Results: We applied parallel DNA methylation and transcriptome sequencing to differentiating human induced pluripotent stem cells to characterize splicing variation (exon skipping) and its determinants. Our results show that variation in single-cell splicing can be accurately predicted based on local sequence composition and genomic features. We observe moderate but consistent contributions from local DNA methylation profiles to splicing variation across cells. A combined model that is built based on genomic features as well as DNA methylation information accurately predicts different splicing modes of individual cassette exons. These categories include the conventional inclusion and exclusion patterns, but also more subtle modes of cell-to-cell variation in splicing. Finally, we identified and characterized associations between DNA methylation and splicing changes during cell differentiation.
Conclusions: Our study yields new insights into alternative splicing at the single-cell level and reveals a previously underappreciated link between DNA methylation variation and splicing.
Predator-prey interactions are vital for organismal survival. They shape anti-predator mechanisms and often depend on sensory abilities. Tadpoles use chemical cues, such as injury cues (alarm cues), to assess predation risks and modify their life-history, morphology, and behaviours accordingly. However, the prevalence of chemically mediated anti-predator responses in species with distinct ecological niches (e.g. within phytotelmata) remains unknown, hindering our understanding of the ecological significance and evolution of alarm substances. Therefore, our study aimed to investigate chemically mediated anti-predator responses in tadpoles of two Neotropical poison dart frogs, Ranitomeya sirensis and Epipedobates anthonyi (and compare their responses to two Palearctic model organisms, Rana temporaria and Bufo bufo, which are known to utilise alarm substances). Through behavioural bioassays, we exposed predator-naïve tadpoles to extracts of each species (i.e. con- and heterospecific cues), including water as a control (i.e. five treatments per species). We assessed changes in their activity before and after stimulus introduction. Our results show that E. anthonyi did not respond to any of the stimuli, whereas R. sirensis displayed increased activity levels exclusively in response to conspecific cues, but not to heterospecific cues. With this, our findings suggest a specialized recognition system in R. sirensis, potentially directed at conspecific competitors but likely unrelated to anti-predator mechanisms. In contrast, E. anthonyi may be insensitive to injury cues or utilize alternative sensory modalities to respond to acute predation events. This study sheds light on the chemical alarm response system of Neotropical poison dart frog tadpoles, providing foundational understanding of how dendrobatids react to injury cues. It prompts questions about the ecological significance and evolutionary implications of chemical communication in species facing extreme resource limitation during development and underscores the importance of comparative research for understanding chemical communication in diverse aquatic ecosystems.
Interacting with the environment to process sensory information, generate perceptions, and shape behavior engages neural networks in brain areas with highly varied representations, ranging from unimodal sensory cortices to higher-order association areas. Recent work suggests a much greater degree of commonality across areas, with distributed and modular networks present in both sensory and non-sensory areas during early development. However, it is currently unknown whether this initially common modular structure undergoes an equally common developmental trajectory, or whether such a modular functional organization persists in some areas—such as primary visual cortex—but not others. Here we examine the development of network organization across diverse cortical regions in ferrets of both sexes using in vivo widefield calcium imaging of spontaneous activity. We find that all regions examined, including both primary sensory cortices (visual, auditory, and somatosensory—V1, A1, and S1, respectively) and higher order association areas (prefrontal and posterior parietal cortices) exhibit a largely similar pattern of changes over an approximately 3 week developmental period spanning eye opening and the transition to predominantly externally-driven sensory activity. We find that both a modular functional organization and millimeter-scale correlated networks remain present across all cortical areas examined. These networks weakened over development in most cortical areas, but strengthened in V1. Overall, the conserved maintenance of modular organization across different cortical areas suggests a common pathway of network refinement, and suggests that a modular organization—known to encode functional representations in visual areas—may be similarly engaged in highly diverse brain areas.
Significance Different areas of the mature brain encode vastly different representations of the world. This study shows that a modular functional organization where nearby neurons participate in similar functional networks is shared across different brain areas not only during early development, but also as the brain matures where it remains a shared feature that shapes neural activity. The largely conserved trajectory of developmental changes across brain areas suggests that similar circuit mechanisms may drive this maturation. This implies that the large literature on developing cortical circuits, which is largely focused on sensory areas, may also apply more broadly, and that perturbations during development that impinge on any such shared mechanisms may produce deficits that extend across multiple brain systems.
A broad range of neuropsychiatric disorders are associated with alterations in macroscale brain circuitry and connectivity. Identifying consistent brain patterns underlying these disorders by means of structural and functional MRI has proven challenging, partly due to the vast number of tests required to examine the entire brain, which can lead to an increase in missed findings. In this study, we propose polyconnectomic score (PCS) as a metric designed to quantify the presence of disease-related brain connectivity signatures in connectomes. PCS summarizes evidence of brain patterns related to a phenotype across the entire landscape of brain connectivity into a subject-level score. We evaluated PCS across four brain disorders (autism spectrum disorder, schizophrenia, attention deficit hyperactivity disorder, and Alzheimer’s disease) and 14 studies encompassing ∼35,000 individuals. Our findings consistently show that patients exhibit significantly higher PCS compared to controls, with effect sizes that go beyond other single MRI metrics ([min, max]: Cohen’s d = [0.30, 0.87], AUC = [0.58, 0.73]). We further demonstrate that PCS serves as a valuable tool for stratifying individuals, for example within the psychosis continuum, distinguishing patients with schizophrenia from their first-degree relatives (d = 0.42, p = 4 x 10−3, FDR-corrected), and first-degree relatives from healthy controls (d = 0.34, p = 0.034, FDR-corrected). We also show that PCS is useful to uncover associations between brain connectivity patterns related to neuropsychiatric disorders and mental health, psychosocial factors, and body measurements.
Purpose: To evaluate intermediate and long-term visual outcomes and safety of a phakic intraocular posterior chamber lens with a central hole (ICL V4c) for myopic eyes.
Methods: Retrospective, consecutive case study of patients that uneventfully received a ICL V4c for myopia correction, with a 5-year postoperative follow-up. Department of Ophthalmology, Goethe University Frankfurt, Germany.
Results: From 241 eyes that underwent ICL implantation, we included 45 eyes with a mean age at surgery of 33 years ± 6 (18–48 years), with a 5 years follow-up. CDVA improved from 0.05logMAR ± 0.15 CDVA preoperatively to − 0.00 ± 0,07 at 5 years and did not change significantly from 3 to 5 years’ time (p = 0.266). The mean spherical equivalent (SE) improved from -10.13D ± 3.39 to − 0.45D ± 0.69. The change in endothelial cell count showed a mean decrease of 1.9% per year throughout the follow-up. Safety and efficacy index were 1.16 and 0.78, respectively. Cataract formation was seen in 2 of 241 eyes (0.8%), but in none of the 45 eyes that finished the 5-year follow-up.
Conclusions: Our data show a good intermediate and long-term stability, efficiency, and safety of ICL V4c phakic lenses in myopic eyes comparable to other known literature.
The category of abelian varieties over Fq is shown to be anti-equivalent to a category of Z-lattices that are modules for a non-commutative pro-ring of endomorphisms of a suitably chosen direct system of abelian varieties over Fq. On full subcategories cut out by a finite set w of conjugacy classes of Weil q-numbers, the anti-equivalence is represented by what we call w-locally projective abelian varieties.
We consider ground state solutions u ∈ H2(RN) of biharmonic (fourth-order) nonlinear Schrodinger equations of the form ¨2u + 2au + bu − |u| p−2u = 0 in RN with positive constants a, b > 0 and exponents 2 < p < 2∗, where 2∗ = 2N N−4 if N > 4 and 2∗ = ∞ if N ≤ 4. By exploiting a connection to the adjoint Stein–Tomas inequality on the unit sphere and by using trial functions due to Knapp, we prove a general symmetry breaking result by showing that all ground states u ∈ H2(RN) in dimension N ≥ 2 fail to be radially symmetric for all exponents 2 < p < 2N+2 N−1 in a suitable regime of a, b > 0. As applications of our main result, we also prove symmetry breaking for a minimization problem with constrained L2-mass and for a related problem on the unit ball in RN subject to Dirichlet boundary conditions.
ABC transporters are found in all organisms and almost every cellular compartment. They mediate the transport of various solutes across membranes, energized by ATP binding and hydrolysis. Dysfunctions can result in severe diseases, such as cystic fibrosis or antibiotic resistance. In type IV ABC transporters, each of the two nucleotide-binding domains is connected to a transmembrane domain by two coupling helices, which are part of cytosolic loops. Although there are many structural snapshots of different conformations, the interdomain communication is still enigmatic. Therefore, we analyzed the function of three conserved, charged residues in the intra-cytosolic loop 1 of the human homodimeric, lysosomal peptide transporter TAPL. Substitution of D278 in coupling helix 1 by alanine interrupted peptide transport by impeding ATP hydrolysis. Alanine substitution of R288 and D292, both localized next to the coupling helix 1 extending to transmembrane helix 3, reduced peptide transport but increased basal ATPase activity. Surprisingly, the ATPase activity of the R288A variant dropped in a peptide-dependent manner while ATPase activity of wildtype and D292A was unaffected. Interestingly, R288A and D292A mutants did not differentiate between ATP and GTP in respect of hydrolysis. However, in contrast to wildtype TAPL, only ATP energized peptide transport. In sum, D278 seems to be involved in bidirectional interdomain communication mediated by network of polar interactions while the two residues in the cytosolic extension of TMH3 are involved in regulation of ATP hydrolysis, most likely by stabilization of the outward facing conformation.
The article discusses the University Library Frankfurt am Main’s current exhibition focusing on the background of and the systematic search for looted assets in the library holdings as part of a wider provenance research project. It offers an overview of various topical areas reaching from initial changes in 1933 to raids throughout Europe by Nazi organisations and restitution procedures during the post-war period. The scope and first findings of the provenance research project will also be addressed.
Der Natrium-abhängige Kaliumkanal Slack (KNa1.1, Slo2.2, KCNT1) nimmt eine Schlüsselrolle in der Regulation neuronaler Erregbarkeit ein, indem er die Ausbildung und Feuerungsfrequenz von Aktionspotentialen kontrolliert. Sowohl in Mäusen als auch in Menschen wird Slack besonders hoch in nicht-peptidergen C-Faser-Neuronen exprimiert. Wissenschaftliche Erkenntnisse der letzten Jahre konnten die Beteiligung von Slack-Kanälen in der Signalverarbeitung neuropathischer Schmerzen, aber auch in verschiedenen Arten von Pruritus, feststellen. Dabei zeigen Slack-defiziente Mäuse ein verstärktes mechanisches Schmerzverhalten nach einer peripheren Nervenverletzung und ein erhöhtes Kratzverhalten in akuten Juckreiz-Modellen. Das als Slack-Aktivator identifizierte trizyklische Neuroleptikum Loxapin zeigt sowohl analgetische als auch antipruritische Effekte in Mäusen, jedoch ist sein klinischer Einsatz auf Grund schwerwiegender antipsychotischer Nebenwirkungen limitiert. Basierend auf Loxapins Leitstruktur wurden daher in dieser Arbeit neue Slack-Aktivatoren mit einem verbesserten pharmakologischen Profil designed und ihr Potential für die Therapie von Schmerzen sowie akutem und chronischem Pruritus in vivo untersucht.
By analyzing 𝑒+𝑒− annihilation data with an integrated luminosity of 2.93 fb−1 collected at the center-of-mass energy √𝑠=3.773 GeV with the BESIII detector, we present the first absolute measurements of the branching fractions of twenty Cabibbo-suppressed hadronic 𝐷0(+) decays involving multiple pions. The highest four branching fractions obtained are ℬ(𝐷0→𝜋+𝜋−𝜋0) = (1.343±0.013stat±0.016syst)%, ℬ(𝐷0→𝜋+𝜋−2𝜋0) = (1.002±0.019stat±0.024syst)%, ℬ(𝐷+→2𝜋+𝜋−𝜋0) = (1.165±0.021stat±0.021syst)%, and ℬ(𝐷+→2𝜋+𝜋−2𝜋0) = (1.074±0.040stat±0.030syst)%. The 𝐶𝑃 asymmetries for the six decays with highest signal yields are also determined and found to be compatible with zero.
By analyzing e+e− annihilation data with an integrated luminosity of 2.93 fb−1 collected at the center-of-mass energy s√= 3.773 GeV with the BESIII detector, we present the first absolute measurements of the branching fractions of twenty Cabibbo-suppressed hadronic D0(+) decays involving multiple pions. The largest four branching fractions obtained are B(D0→π+π−π0) = >(1.343±0.013stat±0.016syst)%, B(D0→π+π−2π0) = (0.998±0.019stat±0.024syst)%, B(D+→2π+π−π0)
(1.174±0.021stat±0.021syst)%, and B(D+→2π+π−2π0) = (1.074±0.040stat±0.030syst)%. The CP asymmetries for the six decays with highest event yields are also determined.
Die Appendizitis stellt mit einer Inzidenz von 115 pro 100000 Einwohnern in Deutschland eine der häufigsten Ursachen für ein akutes Abdomen dar. Bakterielle Infektionen sind ein wesentlicher Faktor für die postoperative Morbidität nach Appendektomie.
Ziel dieser prospektiven Studie war es, das Keimspektrum und insbesondere die Prävalenz resistenter Keime bei der akuten Appendizitis zu bestimmen und die Auswirkungen resistenter Keime auf das Auftreten infektiöser Komplikationen zu analysieren. Alle erwachsenen Patient*innen mit akuter Appendizitis, die zwischen April 2022 und Juli 2023 am Universitätsklinikum Frankfurt operativ behandelt wurden, wurden prospektiv eingeschlossen. Das Keimspektrum der Appendix und die Häufigkeit von MRE in Rektalabstrichen wurden analysiert. Die klinischen Daten wurden extrahiert, um die Korrelation des Keimspektrums mit dem Auftreten von postoperativen Komplikationen, Dauer und Art der Antibiotikatherapie und dem postoperativen Verlauf zu evaluieren. 30 Tage nach der Operation wurde ein Follow-up durchgeführt. Insgesamt wurden 105 Patient*innen in die Studie eingeschlossen.
In den Appendixabstrichen gelang ein Erregernachweis bei 67,6 % aller Fälle. Hierbei betrug die Prävalenz von Keimen mit Antibiotikaresistenz 43,8 %, Multipler-Antibiotikaresistenz (MAR) 27,6 % und bei 5,7 % der Fälle gelang ein MRE-Nachweis nach CDC im Appendixabstrich. Beim MRE-Screening konnten im Rektalabstrich bei 11,4 % der Patient*innen ein MRE nachgewiesen werden. In vier Fällen zeigte sich eine Übereinstimmung zwischen rektalen und appendikulären Abstrich, somit betrug die Sensitivität des MRE-Screenings für einen Nachweis multiresistenter Keime in der Appendix lediglich 33,3 % bei einer Spezifität von 86,7 %. In einer univariaten Analyse konnte das Vorliegen eines Diabetes mellitus als Risikofaktor für das Auftreten von Keimen mit Cefuroxim- Resistenz, Multipler-Antibiotikaresistenz (MAR) und MRE identifiziert werden.
Insgesamt erhielten 47,6 % aller Patient*innen postoperativ eine Antibiotikatherapie, von denen erfolgte bei 46 % eine Umstellung der empirischen Antibiose auf eine antibiogramm-gerechte Therapie nach Erhalt des mikrobiologischen Befundes. Insbesondere Patient*innen mit komplizierter Appendizitis erhielten postoperativ eine Antibiotikatherapie, wobei 28 % eine Antibiotikaeskalation benötigten.
Patient*innen, deren Appendixabstriche eine Resistenz gegen maximal ein Antibiotikum aufwiesen, wurden als nicht multiple Resistenz (Nicht-MAR) definiert und mit Patient*innen verglichen, deren Keime mit multipler Antibiotikaresistenz (MAR) waren. Die MAR-Gruppe zeigte im Vergleich zur Nicht-MAR-Gruppe eine höhere Inzidenz postoperativer Komplikationen, insbesondere eine erhöhte Inzidenz von Clavien-Dindo Grad 3 Komplikationen sowie von tiefen postoperativen Wundinfektionen (CDC Grad A3). Weiterhin benötigten Patient*innen der MAR-Gruppe häufiger eine postoperative Antibiotikatherapie und es erfolgte häufiger eine Eskalation der antibiotischen Therapie. Dies ging auch mit einem signifikant verlängerten Krankenhausaufenthalt einher.
Zusammenfassend kann festgestellt werden, dass eine bakterielle Infektion mit Multipler Antibiotikaresistenz bei der akuten Appendizitis häufig auftritt und die Morbidität nach Appendektomie beeinflusst. Die mikrobiologische Untersuchung mittels Appendixabstrich bei operativ behandelten Fällen von akuter komplizierter Appendizitis, die eine postoperative Antibiotikatherapie erfordern, könnte somit eine gezielte und kürzere Antibiotikatherapie ermöglichen. Dies könnte dazu beitragen, längere Krankenhausaufenthalte zu vermeiden, den unnötigen Einsatz unwirksamer Antibiotika zu reduzieren und die Kosten im Gesundheitswesen zu senken.
Using a sample of (448.1±2.9)×106 𝜓(3686) decays collected with the BESIII detector at BEPCII, we report an observation of Ξ− transverse polarization with a significance of 7.3𝜎 in the decay 𝜓(3686)→Ξ− ¯Ξ+ (Ξ−→Λ𝜋−, ¯Ξ+→¯Λ𝜋+, Λ→𝑝𝜋−, ¯Λ→¯𝑝𝜋+). The relative phase of the electric and magnetic form factors is determined to be ΔΦ=(0.667±0.111±0.058) rad. This is the first measurement of the relative phase for a 𝜓(3686) decay into a pair of Ξ−¯Ξ+ hyperons. The Ξ− decay parameters (𝛼Ξ−, 𝜙Ξ−) and their conjugates (𝛼¯Ξ+, 𝜙¯Ξ+), the angular-distribution parameter 𝛼𝜓, and the strong-phase difference 𝛿𝑝−𝛿𝑠 for Λ𝜋− scattering are measured to be consistent with previous BESIII results.
Luminosities and energies of e⁺e⁻ collision data taken between √s=4.61 GeV and 4.95 GeV at BESIII
(2022)
From December 2019 to June 2021, the BESIII experiment collected about 5.85 fb−1 of data at center-of-mass energies between 4.61 GeV and 4.95 GeV. This is the highest collision energy BEPCII has reached so far. The accumulated e+e− annihilation data samples are useful for studying charmonium(-like) states and charmed-hadron decays. By adopting a novel method of analyzing the production of Λ+cΛ¯−c pairs in e+e− annihilation, the center-of-mass energies are measured with a precision of ∼0.6 MeV. Integrated luminosities are measured with a precision of better than 1\% by analyzing the events of large-angle Bhabha scattering. These measurements provide important inputs to the analyses based on these data samples.
The production cross section of inclusive isolated photons has been measured by the ALICE experiment at the CERN LHC in pp collisions at centre-of-momentum energy of s√=13 TeV collected during the LHC Run 2 data-taking period. The measurement is performed by combining the measurements of the electromagnetic calorimeter EMCal and the central tracking detectors ITS and TPC, covering a pseudorapidity range of |ηγ|<0.67 and a transverse momentum range of 7<pγT<200 GeV/c. The result extends to lower pγT and xγT=2pγT/s√ ranges, the lowest xγT of any isolated photon measurements to date, extending significantly those measured by the ATLAS and CMS experiments towards lower pγT at the same collision energy with a small overlap between the measurements. The measurement is compared with next-to-leading order perturbative QCD calculations and the results from the ATLAS and CMS experiments as well as with measurements at other collision energies. The measurement and theory prediction are in agreement with each other within the experimental and theoretical uncertainties.
A common element of market structure analysis is the spatial representation of firms’ competitive positions on maps. Such maps typically capture static snapshots in time. Yet, competitive positions tend to change. Embedded in such changes are firms’ trajectories, that is, the series of changes in firms’ positions over time relative to all other firms in a market. Identifying these trajectories contributes to market structure analysis by providing a forward-looking perspective on competition, revealing firms’ (re)positioning strategies and indicating strategy effectiveness. To unlock these insights, we propose EvoMap, a novel dynamic mapping framework that identifies firms’ trajectories from high-frequency and potentially noisy data. We validate EvoMap via extensive simulations and apply it empirically to study the trajectories of more than 1,000 publicly listed firms over 20 years. We find substantial changes in several firms’ positioning strategies, including Apple, Walmart, and Capital One. Because EvoMap accommodates a wide range of mapping methods, analysts can easily apply it in other empirical settings and to data from various sources.
Regulators worldwide have been implementing different privacy laws. They vary in their impact on the value for advertisers, publishers and users, but not much is known about these differences. This article focuses on three important privacy laws (i.e., General Data Protection Regulation [GDPR], California Consumer Privacy Act [CCPA] and Personal Information Protection Law [PIPL]) and compares their impact on the value for the three primary actors of the online advertising market, namely, advertisers, publishers and users. This article first compares these three privacy laws by developing a legal strictness score. It then uses the existing literature to derive the effects of the legal strictness of each privacy law on each actor’s value. Finally, it quantifies the three privacy laws’ impact on each actor’s value. The results show that GDPR and PIPL are similar and stricter than CCPA. Stricter privacy laws bring larger negative changes to the value for actors. As a result, both GDPR and PIPL decrease the actors’ value more substantially than CCPA. These value declines are the largest for publishers and are rather similar for users and advertisers. Scholars and practitioners can use our findings to explore ways to create value for multiple actors under various privacy laws.
For many services, consumers can choose among a range of optional tariffs that differ in their access and usage prices. Recent studies indicate that tariff-specific preferences may lead consumers to choose a tariff that does not minimize their expected billing rate. This study analyzes how tariff-specific preferences influence the responsiveness of consumers’ usage and tariff choice to changes in price. We show that consumer heterogeneity in tariff-specific preferences leads to heterogeneity in their sensitivity to price changes. Specifically, consumers with tariff-specific preferences are less sensitive to price increases of their preferred tariff than other consumers. Our results provide an additional reason why firms should offer multiple tariffs rather than a uniform nonlinear pricing plan to extract maximum consumer surplus.
Digitale Technologien begünstigen den Einsatz einer dynamischen Preisgestaltung, also von Preisen, die für ein prinzipiell gleiches Produkt unangekündigt variieren. Dabei werden in der öffentlichen Diskussion unterschiedliche Ausgestaltungsformen dynamischer Preise oftmals vermischt, was eine sinnvolle Analyse der Vor- und Nachteile der dynamischen Preisgestaltung erschwert. Das Ziel des Beitrags ist die Darstellung der ökonomischen Grundlagen und die Diskussion sowie Klassifikation der Ausgestaltungsmöglichkeiten der dynamischen Preisgestaltung. Darüber hinaus erfolgt eine Bewertung der Vor- und Nachteile der dynamischen Preisgestaltung aus Käufer- und Verkäufersicht. Abschließend werden Implikationen für die betriebswirtschaftliche Forschung diskutiert.
Polygene Risikoscores (PRS) integrieren zahlreiche Einzelnukleotid-Polymorphismen (SNP) von meist geringer Effektstärke, um Auskunft über das Erkrankungsrisiko bestimmter Krankheiten zu geben. In dieser Arbeit wurde der PRS zur genetisch generalisierten Epilepsie (GGE) von Leu et al. aus dem Jahr 2019 untersucht, um festzustellen, ob über das Erkrankungsrisiko hinaus noch Korrelationen mit weiteren phänotypischen Eigenschaften von Patienten bestehen. Der Nachweis solcher Zusammenhänge würde eine Prädiktionsfähigkeit des GGE-PRS demonstrieren, die perspektivisch ein Potential für dessen klinische Anwendbarkeit, beispielsweise im Sinne der personalisierten Medizin, aufzeigen könnte.
Die Identifizierung neuer Korrelationen sollte durch Vergleich der Phänotypen von zwei Gruppen von GGE-Patienten mit extrem hohen, beziehungsweise extrem niedrigen PRS-Werten erfolgen. Hierfür wurden von 2256 Patienten aus der Datenbank von Epi25, einem internationalen Forschungskollaborativ zur Erforschung der Relevanz genetischer Faktoren bei der Entwicklung von Epilepsie, die Patienten mit den höchsten (n=59) und den niedrigsten (n=49) GGE-PRS-Werten ausgewählt. Für diese 108 Patienten wurden retrospektive klinische Daten von den jeweiligen Behandlungszentren akquiriert. Hierzu wurde den Studienleitern der Zentren ein Questionnaire mit Fragen zu zahlreichen phänotypischen Parametern der Patienten übermittelt. Die Rücklaufrate war mit 54% gut.
Die so eingeholten Patientendaten wurden anschließend mittels Exaktem Test nach Fisher und Wilcoxon-Rangsummentest statistisch analysiert, um Unterschiede zwischen den Phänotypen beider Gruppen nachzuweisen. Im Falle der Pharmakoresistenz zeichneten sich hierbei zunächst signifikante Unterschiede ab, die ein selteneres Auftreten dieser Eigenschaft für Patienten mit hohen GGE-PRS-Werten implizierten. Diese Ergebnisse waren jedoch nach einer Bonferroni-Korrektur und bei Validierung in einer größeren Kohorte (n=825) nicht mehr signifikant. Für die anderen untersuchten Parameter waren ebenfalls keine signifikanten Unterschiede nachweisbar.
Das Ergebnis, dass für keinen der untersuchten Parameter signifikante Differenzen bestanden, obwohl zwei Kohorten mit extrem gegensätzlichen PRS-Werten untersucht wurden, spricht gegen eine Verwendung des aktuell verfügbaren GGE-PRS als prädiktiver Biomarker über das Erkrankungsrisiko hinaus und somit gegen dessen klinische Anwendbarkeit. Jedoch können die nicht-signifikanten Korrelationen im Falle der Pharmakoresistenz als Hinweis verstanden werden, dass im Bereich der Pharmakotherapie Zusammenhänge zwischen Score und Phänotyp bestehen könnten, die weiterer Untersuchungen in zukünftigen Studien bedürfen. Bei Verwendung eines verbesserten GGE-PRS mit zusätzlichen risikoassoziierten SNP und verfeinerter Wichtung der Effektstärken sowie größerer Kohorten könnten in diesem Bereich möglicherweise auch signifikante Zusammenhänge nachweisbar werden.
Exploring strategies to improve the reverse beta-oxidation pathway in Saccharomyces cerevisiae
(2024)
Microbes are the most diverse living organisms on Earth, with various metabolic adaptations that allow them to live in different conditions and produce compounds with different chemical complexity. Microbial biotechnology exploits the metabolic diversity of microorganisms to manufacture products for different industries. Today, the chemical industry is a significant energy consumer and carbon dioxide emitter, with processes that harm natural ecosystems, like the extraction of medium-chain fatty acids (MCFAs). MCFAs are used as precursors for biofuels, volatile esters, surfactants, or polymers in materials with enhanced properties.
However, their current extraction process uses large, non-sustainable monocultures of coconut and palm trees. Therefore, the microbial production of MCFAs can help reduce the current environmental impact of obtaining these products and their derivatives.
In nature, fatty acids are mostly produced via fatty acid biosynthesis (FAB). However, the reverse β-oxidation (rBOX) is a more energy-efficient pathway compared to FAB. The rBOX pathway consists of four reactions, which result in the elongation of an acyl-CoA molecule by two carbon units from acetyl-CoA in each cycle. In this work we used Saccharomyces cerevisiae, an organism with a high tolerance towards toxic compounds, as the expression host of the rBOX pathway to produce MCFAs and medium-chain fatty alcohols (MCFOHs).
In the first part of this work, we expanded the length of the products from expressing the rBOX in the cytosol and increased the MCFAs titres. First, we deleted the major glycerol-3-phosphate dehydrogenase (GPD2). This resulted in a platform strain with significantly reduced glycerol fermentation and increased rBOX pathway activity, probably due to an increased availability of NADH. Then, we tested different combinations of rBOX enzymes to increase the length and titres of MCFA. Expressing the thiolase CnbktB and β-hydroxyacyl-CoA dehydrogenase CnpaaH1 from Cupriavidus necator, Cacrt from Clostridium acetobutylicum and the trans-enoyl-CoA reductase Tdter (Treponema denticola) resulted in hexanoic acid as the main product.
Expressing Cncrt2 (C. necator) or YlECH (Y. lipolytica) as enoyl-CoA hydratases resulted in octanoic acid as the main product. Then, we integrated the octanoic (Cncrt2 or YlECH) and the hexanoic acid (Cacrt)-producing variants in the genome of the platform strain and we achieved titers of ≈75 mg/L (hexanoic acid) and ≈ 60 mg/L (octanoic acid) when growing these strains in a complex, highly buffered medium. These are the highest titers of octanoic and hexanoic acid obtained in S. cerevisiae with the rBOX. Additionally, we deleted TES1 and FAA2 to prevent competition for butyryl-CoA and degradation of the produced fatty acids, respectively.
However, these deletions did not improve MCFA titers. In addition, we tested two dual acyl-CoA reductase/alcohol dehydrogenases (ACR/ADH), CaadhE2 from C. acetobutylicum and the putative ACR/ADH EceutE from Escherichia coli, in an octanoyl-CoA-producing strain to produce MCFOH. As a result, we produced 1-hexanol and 1-octanol for the first time in S. cerevisiae with these two enzymes. Nonetheless, the titres were low (<10 mg/L and <2 mg/L, respectively), and four-carbon 1-butanol was the main product in both cases (>80 mg/L). This showed the preference of these two enzymes for butyryl-CoA.
In the second part of this work, we expressed the rBOX in the mitochondria of S. cerevisiae to benefit from the high levels of acetyl-CoA and the reducing environment in that organelle. First, in an adh-deficient strain, we mutated MTH1, a transcription factor regulating the expression of hexose transporters, and deleted GPD2. This resulted in a strain with a reduced Crabtree effect and, therefore, an increased carbon flux to the mitochondria. We partially validated the increased flux to the mitochondria by expressing the ethanol-acetyltransferase EAT1 from Kluyveromyces marxianus in this organelle. This resulted in a higher isoamyl acetate production in the MTH1-mutant strain. Isoamyl acetate is synthesised by Eat1 from acetyl-CoA and isoamyl alcohol, a product of the metabolism of amino acids in the mitochondria. Then, we targeted different butyryl-CoA-producing rBOX variants to the mitochondria, and we used the production of 1-butanol and butyric acid as a proof-of-concept. The strong expression of all the enzymes was toxic for the cell, and the highest butyric acid titres (≈ 50 mg/L) in the mitochondria from the rBOX were obtained from the weak expression of the pathway. The highest 1-butanol titers (≈ 5 mg/L) were obtained with the downregulation of the mitochondrial NADH-oxidase NDI1. However, this downregulation led to a non-desirable petite phenotype.
In summary, we produced hexanoic and octanoic acid for the first time in S. cerevisiae using the rBOX and achieved the highest reported titers of hexanoic and octanoic acid so far using this pathway in S. cerevisiae. In addition, we successfully compartmentalised the rBOX in the mitochondria. However, competing reactions, some of them essential for the viability of the cell, limit the use of this organelle for the rBOX.
Background: Prostate cancer is a major health concern in aging men. Paralleling an aging society, prostate cancer prevalence increases emphasizing the need for efcient diagnostic algorithms.
Methods: Retrospectively, 106 prostate tissue samples from 48 patients (mean age,
66 ± 6.6 years) were included in the study. Patients sufered from prostate cancer (n = 38) or benign prostatic hyperplasia (n = 10) and were treated with radical prostatectomy or Holmium laser enucleation of the prostate, respectively. We constructed tissue microarrays (TMAs) comprising representative malignant (n = 38) and benign (n = 68) tissue cores. TMAs were processed to histological slides, stained, digitized and assessed for the applicability of machine learning strategies and open–source tools in diagnosis of prostate cancer. We applied the software QuPath to extract features for shape, stain intensity, and texture of TMA cores for three stainings, H&E, ERG, and PIN-4. Three machine learning algorithms, neural network (NN), support vector machines (SVM), and random forest (RF), were trained and cross-validated with 100 Monte Carlo random splits into 70% training set and 30% test set. We determined AUC values for single color channels, with and without optimization of hyperparameters by exhaustive grid search. We applied recursive feature elimination to feature sets of multiple color transforms.
Results: Mean AUC was above 0.80. PIN-4 stainings yielded higher AUC than H&E and
ERG. For PIN-4 with the color transform saturation, NN, RF, and SVM revealed AUC of 0.93 ± 0.04, 0.91 ± 0.06, and 0.92 ± 0.05, respectively. Optimization of hyperparameters improved the AUC only slightly by 0.01. For H&E, feature selection resulted in no increase of AUC but to an increase of 0.02–0.06 for ERG and PIN-4.
Conclusions: Automated pipelines may be able to discriminate with high accuracy between malignant and benign tissue. We found PIN-4 staining best suited for classifcation. Further bioinformatic analysis of larger data sets would be crucial to evaluate the reliability of automated classifcation methods for clinical practice and to evaluate potential discrimination of aggressiveness of cancer to pave the way to automatic precision medicine.
Climate change affects ecosystems worldwide and is threatening biodiversity. Insects, as ectotherm organisms, are strongly dependent on the thermal environment. Yet, little is known about the effects of summer heat and drought on insect diversity. In the Mediterranean climate zone, a region strongly affected by climate change, hot summers might have severe effects on insect communities. Especially the larval stage might be sensitive to thermal variation, as larvae—compared to other life stages—cannot avoid hot temperatures and drought by dormancy. Here we ask, whether inter-annual fluctuations in Mediterranean moth diversity can be explained by temperature (TLarv) and precipitation during larval development (HLarv). To address our question, we analyzed moth communities of a Mediterranean coastal forest during the last 20 years. For species with summer-developing larvae, species richness was significantly negatively correlated with TLarv, while the community composition was affected by both, TLarv and HLarv. Therefore, summer-developing larvae seem particularly sensitive to climate change, as hot summers might exceed the larval temperature optima and drought reduces food plant quality. Increasing frequency and severity of temperature and drought extremes due to climate change, therefore, might amplify insect decline in the future.
This prospective study sought to evaluate potential savings of radiation dose to medical staff using real-time dosimetry coupled with visual radiation dose feedback during angiographic interventions. For this purpose, we analyzed a total of 214 angiographic examinations that consisted of chemoembolizations and several other types of therapeutic interventions. The Unfors RaySafe i2 dosimeter was worn by the interventionalist at chest height over the lead protection. A total of 110 interventions were performed with real-time radiation dosimetry allowing the interventionalist to react upon higher x-ray exposure and 104 examinations served as the comparative group without real-time radiation monitoring. By using the real-time display during interventions, the overall mean operator radiation dose decreased from 3.67 (IQR, 0.95–23.01) to 2.36 μSv (IQR, 0.52–12.66) (−36%; p = 0.032) at simultaneously reduced operator exposure time by 4.5 min (p = 0.071). Dividing interventions into chemoembolizations and other types of therapeutic interventions, radiation dose decreased from 1.31 (IQR, 0.46-3.62) to 0.95 μSv (IQR, 0.53-3.11) and from 24.39 (IQR, 12.14-63.0) to 10.37 μSv (IQR, 0.85-36.84), respectively, using live-screen dosimetry (p ≤ 0.005). Radiation dose reductions were also observed for the participating assistants, indicating that they could also benefit from real-time visual feedback dosimetry during interventions (−30%; p = 0.039). Integration of real-time dosimetry into clinical processes might be useful in reducing occupational radiation exposure time during angiographic interventions. The real-time visual feedback raised the awareness of interventionalists and their assistants to the potential danger of prolonged radiation exposure leading to the adoption of radiation-sparing practices. Therefore, it might create a safer environment for the medical staff by keeping the applied radiation exposure as low as possible.
Biodiversity patterns of marine crustaceans are still unknown in many locations or might have been overlooked due to our knowledge gaps, despite increasing sampling and data sharing efforts during the last decades. By analysing big data extracted from open portals such as Ocean Biodiversity Information System (OBIS) and Global Biodiversity Information System (GBIF), we aim to revisit the distribution and biodiversity patterns of the highly speciose and abundant Crustacea in the Northwest Pacific (NWP) from shallowest depths to the deep sea. This study focussed on selected benthic and pelagic crustacean (sub) classes and their species richness, sampling effort, and expected species richness (ES50) using equal/sized hexagonal cells, 5° latitudinal bands, 500 m depth intervals were analyzed. Crustacean species richness was highest in the tropical Philippines as well as around the Japanese islands. Pelagic crustacean species richness peaked at 30° latitude and declined beyond that. Benthic taxa; however, depicted high levels of species richness across most of the latitudinal gradient, reaching its highest point at 45° latitude. Due to the prevalence of certain crustacean orders in the deep sea, benthic species richness showed a distribution pattern with two distinct peaks across bathymetric gradients; with highest species richness recorded at shallow-water depths and also at abyssal depths. The most important environmental drivers of benthic and pelagic crustacean species richness were primary productivity (positive correlation) and salinity (negative correlation). Our study provides first insights into biodiversity patterns of the highly diverse Crustacea in the NWP and highlights strong differences between benthic and pelagic taxa. The results presented here could help us to better understand whether benthic or pelagic taxa might respond differently to climate changes in the NWP based on their distinct physiological and biological characteristics. This information is crucial in establishing species management strategies and ecosystem restorations in both shallow water and deep-sea environments.
The combination of histological and biomolecular analyses provides deep understanding of different biological processes and is of high interest for basic and applied research. However, the available analytical methods are still limited, especially when considering bone samples. This study compared different fixation media to identify a sufficient analytical method for the combination of histological, immuno-histological and biomolecular analyses of the same fixed, processed and paraffin embedded bone sample. Bone core biopsies of rats’ femurs were fixed in different media (RNAlater + formaldehyde (R + FFPE), methacarn (MFPE) or formaldehyde (FFPE)) for 1 week prior to decalcification by EDTA and further histological processing and paraffin embedding. Snap freezing (unfixed frozen tissue, UFT) and incubation in RNAlater were used as additional controls. After gaining the paraffin sections for histological and immunohistological analysis, the samples were deparaffined and RNA was isolated by a modified TRIZOL protocol. Subsequently, gene expression was evaluated using RT-qPCR. Comparable histo-morphological and immuno-histological results were evident in all paraffin embedded samples of MFPE, FFPE and R + FFPE. The isolated RNA in the group of MFPE showed a high concentration and high purity, which was comparable to the UFT and RNAlater groups. However, in the groups of FFPE and R + FFPE, the RNA quality and quantity were statistically significantly lower when compared to MFPE, UFT and RNAlater. RT-qPCR results showed a comparable outcome in the group of MFPE and UFT, whereas the groups of FFPE and R + FFPE did not result in a correctly amplified gene product. Sample fixation by means of methacarn is of high interest for clinical samples to allow a combination of histological, immunohistological and biomolecular analysis. The implementation of such evaluation method in clinical research may allow a deeper understanding of the processes of bone formation and regeneration.
Alternating acquisition of background and sample spectra is often employed in conventional Fourier-transform infrared spectroscopy or ultraviolet–visible spectroscopy for accurate background subtraction. For example, for solvent background correction, typically a spectrum of a cuvette with solvent is measured and subtracted from a spectrum of a cuvette with solvent and solute. Ultrafast spectroscopies, though, come with many peculiarities that make the collection of well-matched, subtractable background and sample spectra challenging. Here, we present a demountable split-sample cell in combination with a modified Lissajous scanner to overcome these challenges. It allows for quasi-simultaneous measurements of background and sample spectra, mitigating the effects of drifts of the setup and maintaining the beam and sample geometry when swapping between background and sample measurements. The cell is moving between subsequent laser shots to refresh the excited sample volume. With less than 45 μl of solution for 150 μm optical thickness, sample usage is economical. Cell assembly is a key step and covered in an illustrated protocol.
Hepatic cells are sensitive to internal and external signals. Ethanol is one of the oldest and most widely used drugs in the world. The focus on the mechanistic engine of the alcohol-induced injury has been in the liver, which is responsible for the pathways of alcohol metabolism. Ethanol undergoes a phase I type of reaction, mainly catalyzed by the cytoplasmic enzyme, alcohol dehydrogenase (ADH), and by the microsomal ethanol-oxidizing system (MEOS). Reactive oxygen species (ROS) generated by cytochrome (CYP) 2E1 activity and MEOS contribute to ethanol-induced toxicity. We aimed to: (1) Describe the cellular, pathophysiological and clinical effects of alcohol misuse on the liver; (2) Select the biomarkers and analytical methods utilized by the clinical laboratory to assess alcohol exposure; (3) Provide therapeutic ideas to prevent/reduce alcohol-induced liver injury; (4) Provide up-to-date knowledge regarding the Corona virus and its affect on the liver; (5) Link rare diseases with alcohol consumption. The current review contributes to risk identification of patients with alcoholic, as well as non-alcoholic, liver disease and metabolic syndrome. Additional prevalence of ethnic, genetic, and viral vulnerabilities are presented.
Mitochondrial RNA granules (MRGs) are membraneless, highly specialized compartments that play an essential role in the post-transcriptional regulation of mitochondrial gene expression. This regulation is crucial for maintaining energy production, controlling metabolic functions and ensuring homeostasis in cells. Dysregulation of mitochondrial genes has been linked to various human diseases, including neurodegenerative and metabolic disorders as well as certain types of cancer.
MRGs are composed of different RNA species, including mitochondrial precursor RNA (pre-RNA), mature tRNAs, rRNAs and mRNAs complexed with multiple proteins involved in RNA processing and mitoribosome assembly. However, despite the significance of MRGs, their protein composition, structural organization, stability and dynamics during stress conditions remain elusive. In the study reported here, I adopted a three-step approach to address the aforementioned fundamental issues.
First and foremost, I identified the protein composition of MRGs and unveiled their architectural complexity. To characterize the MRG proteome, I applied the cutting-edge TurboID-based proximity labeling approach combined with quantitative mass spectrometry. Proximity labeling was conducted on 20 distinct MRG-associated human proteins, resulting in the identification of more than 1,700 protein-protein interactions. This expansive dataset enabled me to create a comprehensive network, providing valuable insights into both the (sub)architecture as well as the core structure of MRGs in-depth.
Secondly, I investigated the spatio-temporal dynamics of MRGs under various mitochondrial stress conditions. To monitor the morphological alterations and compositional changes of MRGs, I utilized time-resolved confocal fluorescence microscopy and proteomics, respectively. In this analysis, I applied IMT1, the first specific inhibitor that selectively targets mitochondrial transcription. Using this methodology, I pinpointed precise conditions that triggered MRGs’ disassembly during stress, followed by their reassembly when nascent RNA production was restored. The results of this examination elucidate that MRGs are highly dynamic and stress adaptive structures, capable of rapid dissolution and reassembly, a process closely connected to mitochondrial transcription.
Thirdly, I aimed to explore the impact of RNA turnover on MRGs’ integrity during stress, employing confocal fluorescence microscopy and quantitative real-time PCR. I observed that depletion of MRG proteins associated with RNA degradation counteracts MRGs’ disassembly under stress conditions, a phenomenon attributed to the accumulation of double-stranded RNA (dsRNA). These results emphasize the critical role of pre-RNA turnover in maintaining MRG integrity and reveal that MRGs can be stabilized by dsRNA.
Taken together, the comprehensive investigation reported in this thesis has substantially broadened and deepened our understanding of MRGs’ complexity. By identifying their molecular structure and dynamics, I have gained significant insights into the fundamental characteristics and biological functions of MRGs in cellular processes. This knowledge contributes to the identification of disease-related pathways linked to mitochondrial gene expression and may inspire future studies to develop novel therapeutic approaches.
Growing up in cities is associated with increased risk for developing mental health problems. Stress exposure and altered stress regulation have been proposed as mechanisms linking urbanicity and psychopathology, with most research conducted in adult populations. Here, we focus on early childhood, and investigate urbanicity, behavior problems and the regulation of the hypothalamus-pituitary-adrenal (HPA) axis, a central circuit of the stress system, in a sample of N = 399 preschoolers aged 45 months. Urbanicity was coded dichotomously distinguishing between residences with more or less than 100,000 inhabitants. Behavior problems were measured using the Child Behavior Checklist (CBCL) 1½ - 5. Cortisol stress reactivity was assessed using an age-appropriated game-like stress task, and cortisol in the first morning urine was measured to assess nocturnal HPA axis activity. Urbanicity was not associated with behavior problems, urinary cortisol or the cortisol stress response. Neither urinary cortisol nor salivary cortisol response after stress exposure were identified as mediators of the relationship between urbanicity and behavior problems. The findings suggest no strong association of urbanicity with behavior problems and HPA axis regulation in preschool age. To our knowledge, this is the youngest sample to date studying the relationship between urbanicity and behavior problems as well as HPA axis regulation. Future research should examine at which age associations can first be identified and which mechanisms contribute to these relationships.
Aim
To compare overall mortality (OM), cancer-specific mortality (CSM), and other cause mortality (OCM) rates between radical prostatectomy (RP) versus radiotherapy (RT) in clinical node-positive (cN1) prostate cancer (PCa).
Materials and Methods
Within Surveillance, Epidemiology, End Results (SEER) (2004–2016), we identified 4685 cN1 PCa patients, of whom 3589 (76.6%) versus 1096 (24.4%) were treated with RP versus RT. After 1:1 propensity score matching (PSM), Kaplan–Meier plots and Cox regression models tested the effect of RP versus RT on OM, while cumulative incidence plots and competing-risks regression (CRR) models addressed CSM and OCM between RP and RT patients. All analyses were repeated after the inverse probability of treatment weighting (IPTW). For CSM and OCM analyses, the propensity score was used as a covariate in the regression model.
Results
Overall, RT patients were older, harbored higher prostate-specific antigen values, higher clinical T and higher Gleason grade groups. PSM resulted in two equally sized groups of 894 RP versus 894 RT patients. After PSM, 5-year OM, CSM, and OCM rates were, respectively, 15.4% versus 25%, 9.3% versus 17%, and 6.1% versus 8% for RP versus RT (all p < 0.001) and yielded respective multivariate hazard ratios (HRs) of 0.63 (0.52–0.78, p < 0.001), 0.66 (0.52–0.86, p < 0.001), 0.71 (0.5–1.0, p = 0.05), all favoring RP. After IPTW, Cox regression models yielded HR of 0.55 (95% confidence interval [CI] = 0.46–0.66) for OM, and CRR yielded HRs of 0.49 (0.34–0.70) and 0.54 (0.36–0.79) for, respectively, CSM and OCM, all favoring RP (all p < 0.001).
Conclusions
RP may hold a CSM advantage over RT in cN1 PCa patients.
The intensity and the features of sensory stimuli are encoded in the activity of neurons in the cortex. In the visual and piriform cortices, the stimulus intensity rescales the activity of the population without changing its selectivity for the stimulus features. The cortical representation of the stimulus is therefore intensity invariant. This emergence of network-invariant representations appears robust to local changes in synaptic strength induced by synaptic plasticity, even though (i) synaptic plasticity can potentiate or depress connections between neurons in a feature-dependent manner, and (ii) in networks with balanced excitation and inhibition, synaptic plasticity determines the nonlinear network behavior. In this study we investigate the consistency of invariant representations with a variety of synaptic states in balanced networks. By using mean-field models and spiking network simulations, we show how the synaptic state controls the emergence of intensity-invariant or intensity-dependent selectivity. In particular, we demonstrate that an effective power-law synaptic transformation at the population level is necessary for invariance. In a range of firing rates, purely depressing short-term synapses fulfills this condition, and in this case, the network is contrast-invariant. Instead, facilitating short-term plasticity generally narrows the network selectivity. We found that facilitating and depressing short-term plasticity can be combined to approximate a power-law that leads to contrast invariance. These results explain how the physiology of individual synapses is linked to the emergence of invariant representations of sensory stimuli at the network level.
A plethora of modified nucleotides extends the chemical and conformational space for natural occurring RNAs. tRNAs constitute the class of RNAs with the highest modification rate. The extensive modification modulates their overall stability, the fidelity and efficiency of translation. However, the impact of nucleotide modifications on the local structural dynamics is not well characterized. Here we show that the incorporation of the modified nucleotides in tRNAfMet from Escherichia coli leads to an increase in the local conformational dynamics, ultimately resulting in the stabilization of the overall tertiary structure. Through analysis of the local dynamics by NMR spectroscopic methods we find that, although the overall thermal stability of the tRNA is higher for the modified molecule, the conformational fluctuations on the local level are increased in comparison to an unmodified tRNA. In consequence, the melting of individual base pairs in the unmodified tRNA is determined by high entropic penalties compared to the modified. Further, we find that the modifications lead to a stabilization of long-range interactions harmonizing the stability of the tRNA’s secondary and tertiary structure. Our results demonstrate that the increase in chemical space through introduction of modifications enables the population of otherwise inaccessible conformational substates.
Research in social insects has shown that hydrocarbons on their cuticle are species-specific. This has also been proven for Diptera and is a promising tool for identifying important fly taxa in Forensic Entomology. Sometimes the empty puparia, in which the metamorphosis to the adult fly has taken place, can be the most useful entomological evidence at the crime scene. However, so far, they are used with little profit in criminal investigations due to the difficulties of reliably discriminate among different species. We analysed the CHC chemical profiles of empty puparia from seven forensically important blow flies Calliphora vicina, Chrysomya albiceps, Lucilia caesar, Lucilia sericata, Lucilia silvarum, Protophormia terraenovae, Phormia regina and the flesh fly Sarcophaga caerulescens. The aim was to use their profiles for identification but also investigate geographical differences by comparing profiles of the same species (here: C. vicina and L. sericata) from different regions. The cuticular hydrocarbons were extracted with hexane and analysed using gas chromatography-mass spectrometry. Our results reveal distinguishing differences within the cuticular hydrocarbon profiles allowing for identification of all analysed species. There were also differences shown in the profiles of C. vicina from Germany, Spain, Norway and England, indicating that geographical locations can be determined from this chemical analysis. Differences in L. sericata, sampled from England and two locations in Germany, were less pronounced, but there was even some indication that it may be possible to distinguish populations within Germany that are about 70 km apart from one another.
With the introduction of the virtual allocation crossmatch in the Eurotransplant (ET) region in 2023, the determination of unacceptable antigen mismatches (UAM) in kidney transplant recipients is of utmost importance for histocompatibility laboratories and transplant centers. Therefore, a joined working group of members from the German Society for Immunogenetics (Deutsche Gesellschaft für Immungenetik, DGI) and the German Transplantation Society (Deutsche Transplantationsgesellschaft, DTG) revised and updated the previous recommendations from 2015 in light of recently published evidence. Like in the previous version, a wide range of topics is covered from technical issues to clinical risk factors. This review summarizes the evidence about the prognostic value of contemporary methods for HLA antibody detection and identification, as well as the impact of UAM on waiting time, on which these recommendations are based. As no clear criteria could be determined to differentiate potentially harmful from harmless HLA antibodies, the general recommendation is to assign all HLA against which plausible antibodies are found as UAM. There is, however, a need for individualized solutions for highly immunized patients. These revised recommendations provide a list of aspects that need to be considered when assigning UAM to enable a fair and comprehensible procedure and to harmonize risk stratification prior to kidney transplantation between transplant centers.
Mining is one of the major pollution sources worldwide, causing huge disturbances to the environment. Industrial and artisanal mining activities are widespread in Mexico, a major global producer of various metals. This study aimed to assess the ecological impairments resulting from mining activities using aquatic macroinvertebrates assemblages (MA). A multiple co-inertia analysis was applied to determine the relationships between environmental factors, habitat quality, heavy metals, and aquatic macroinvertebrates in 15 study sites in two different seasons (dry and wet) along two rivers running across the Central Plateau of Mexico. The results revealed three contrasting environmental conditions associated with different MAs. High concentrations of heavy metals, nutrients, and salinity limit the presence of several families of seemingly sensitive macroinvertebrates. These factors were found to influence structural changes in MAs, showing that not only mining activities, but also agriculture and presence of villages in the basin, exert adverse effects on macroinvertebrate assemblages. Diversity indices showed that the lowest diversity matched both the most polluted and the most saline rivers. The rivers studied displayed high alkalinity and hardness levels, which can reduce the availability of metals and cause adverse effects on periphyton by inhibiting photosynthesis and damaging MAs. Aquatic biomonitoring in rivers, impacted by mining and other human activities, is critical for detecting the effect of metals and other pollutants to improve management and conservation strategies. This study supports the design of cost-effective and accurate water quality biomonitoring protocols in developing countries.
Matter-antimatter asymmetry is a research topic of fundamental interest, as it is the basis for the existence of the matter world, which survived annihilation with antimatter in the early Universe. High energy nuclear collisions create conditions similar to the Universe microseconds after the Big Bang, with comparable amounts of matter and antimatter. Much of the antimatter created escapes the rapidly expanding fireball without annihilation, making such collisions an effective experimental tool to create heavy antimatter nuclear objects and study their properties. In this paper, we report the first observation of the antimatter hypernucleus 4Λ¯H¯¯¯¯, composed of an Λ¯, an antiproton and two antineutrons. The discovery was made through its two-body decay after production in ultrarelativistic heavy ion collisions by the STAR experiment at the Relativistic Heavy Ion Collider. In total, 15.6 candidate 4Λ¯H¯¯¯¯ antimatter hypernuclei are obtained with an estimated background count of 6.4. Lifetimes of the antihypernuclei 3Λ¯H¯¯¯¯ and 4Λ¯H¯¯¯¯ are measured and compared with lifetimes of their corresponding hypernuclei, testing the symmetry between matter and antimatter. Various production yield ratios among (anti)hypernuclei and (anti)nuclei are also measured and compared with theoretical model predictions, shedding light on their production mechanism.
Antimatter is a research topic of fundamental interest. Sufficient matter-antimatter asymmetry in the early Universe created the matter-dominated world today. The origin of this asymmetry is not completely understood to date. High-energy nuclear collisions create conditions similar to the Universe microseconds after the Big Bang, with comparable amounts of matter and antimatter. Much of the antimatter created escapes the rapidly expanding fireball without annihilation, making such collisions an effective experimental tool to create heavy antimatter nuclear objects and study their properties. In this paper, we report the first observation of the antimatter hypernucleus 4Λ¯H¯¯¯¯, composed of an Λ¯, an antiproton and two antineutrons. The discovery was made through its two-body decay after production in ultrarelativistic heavy-ion collisions by the STAR experiment at the Relativistic Heavy Ion Collider. In total, 15.6 candidate 4Λ¯H¯¯¯¯ antimatter hypernuclei are obtained with an estimated background count of 6.4. Lifetimes of the antihypernuclei 3Λ¯H¯¯¯¯ and 4Λ¯H¯¯¯¯ are measured and compared with the lifetimes of their corresponding hypernuclei, testing the symmetry between matter and antimatter. Various production yield ratios among (anti)hypernuclei and (anti)nuclei are also measured and compared with theoretical model predictions, shedding light on their production mechanism.
Inflammation is a crucial host defense mechanism activated in response to injury or infection. Its primary goal is to eliminate the source of the disturbance, repair the damaged tissue, and restore homeostasis. Inflammatory processes can be recognized through increased blood flow, higher vascular permeability, and the recruitment of leukocytes and plasma proteins to the tissue. A pathogen-induced inflammation triggers various pro- and anti-inflammatory processes. Local tissue cells and Toll-like receptors call upon innate immune cells like neutrophils, dendritic cells (DCs), and monocytes to respond to the intruder. They move across the endothelium and respond to local signals by releasing mediators or cytotoxic compounds, phagocytosing, or polarizing. To study local pathogen-induced inflammation, a zymosan-induced inflammation model was used in the hind paws of mice, which caused a Toll-like receptor 2 mediated inflammation. Multi-Epitope-Ligand-Cartography (MELC) was used for multiple sequential immunohistochemistry with 40 different antibodies on the same tissue. Bioinformatic analysis and graphical representation revealed a specific inflammatory architecture consisting of three major areas based on macrophage polarization and their cellular neighborhoods: a core region containing the pathogen, a pro-inflammatory region containing M1-like macrophages, and a region containing anti-inflammatory cells. This discovery highlights the coexistence of pro- and antiinflammatory processes during an ongoing inflammation and challenges the concept of a gradual temporal transition from pro- to anti-inflammation. Flow cytometry of the whole paw was performed to support and refine the MELC results. Eosinophils were used as a specific immune cell population to investigate their role in the inflammatory structure. They were found to be present in all three inflammatory regions, adapting their cytokine profile according to their localization. Depleting eosinophils reduced Interleukin 4 (IL-4)- levels, increased edema formation, and mechanical and thermal hypersensitivities during inflammation resolution. In the absence of eosinophils, pro- and anti-inflammatory region could not be determined in the inflammatory architecture, neutrophil numbers increased, and efferocytosis and M2-macrophage polarization were reduced. IL-4 administration restored these regions, normalized neutrophil numbers, efferocytosis, M2-macrophage polarization, and resolution of zymosan-induced hypersensitivity. The results show that eosinophils expressing IL-4 support the resolution of inflammation by enabling the development of an anti-inflammatory framework that encloses pro-inflammatory regions.
Generative AI is a game changer – also in the financial sector. Institutions and their IT service providers need to consider carefully: Which AI approach will enable them to implement optimal solutions for themselves and their customers in this highly regulated environment? How did Finanz Informatik, as the savings banks’ digitalization partner, proceed here?
The significance of data and Artificial Intelligence (AI) has a profound impact on all industries, presenting both challenges and opportunities. Given its power and relevance, AI has not gone unnoticed in the public affairs sector. The upcoming German federal election in 2025 brings discussions about AI to the forefront, raising questions about the extent to which data will drive the public affairs field and how it will be handled.
Customer loyalty is a critical measure for success, showing if a firm's product is received well by its customers. To understand its development over time, two fundamental questions must be answered: (I) How will current customers' loyalty develop, and (II) will new customers' loyalty differ from current customers' loyalty? The authors empirically answer these questions based on a data set including ~500 B2B web technologies with jointly ~325 million customers spanning over 24 years. They show that loyalty hardly develops and, if so, it rather decreases than increases. The loyalty of current customers rarely changes and, if so, rather increases than decreases. New customers are most likely less loyal than current customers. These results show that by failing to account for these underlying developments, stakeholders, in most cases, draw the wrong conclusions about product value measured via customer lifetime value.
Existing table retrieval approaches estimate each table’s relevance for a particular information need and return a ranking of the most relevant tables. This approach is not ideal since the returned tables often include irrelevant data and the required information may be scattered across multiple tables. To address these issues, we propose the idea of fine-grained structured table retrieval and present our vision of R2D2, a system which slices tables into small tiles that are later composed into a structured result that is tailored to the user-provided information need. An initial evaluation of our approach demonstrates how our idea can improve table retrieval and relevant downstream tasks such as table question answering.
Using about 23 fb−1 of data collected with the BESIII detector operating at the BEPCII storage ring, a precise measurement of the 𝑒+𝑒−→𝜋+𝜋−𝐽/𝜓 Born cross section is performed at center-of-mass energies from 3.7730 to 4.7008 GeV. Two structures, identified as the 𝑌(4220) and the 𝑌(4320) states, are observed in the energy-dependent cross section with a significance larger than 10𝜎. The masses and widths of the two structures are determined to be (𝑀,Γ)=(4221.4±1.5±2.0 MeV/𝑐2,41.8±2.9±2.7 MeV) and (𝑀,Γ)=(4298±12±26 MeV/𝑐2,127±17±10 MeV), respectively. A small enhancement around 4.5 GeV with a significance about 3𝜎, compatible with the 𝜓(4415), might also indicate the presence of an additional resonance in the spectrum. The inclusion of this additional contribution in the fit to the cross section affects the resonance parameters of the 𝑌(4320) state.
Observation of ηc(2S) → 3(π⁺π⁻) and measurements of χcJ → 3(π⁺π⁻) in ψ(3686) radiative transitions
(2022)
The hadronic decay 𝜂𝑐(2𝑆)→3(𝜋+𝜋−) is observed with a statistical significance of 9.3 standard deviations using (448.1±2.9)×106 𝜓(3686) events collected by the BESIII detector at the BEPCII collider. The measured mass and width of 𝜂𝑐(2𝑆) are (3643.4±2.3 (stat)±4.4 (syst)) MeV/𝑐2 and (19.8±3.9 (stat)±3.1 (syst)) MeV, respectively, which are consistent with the world average values within two standard deviations. The product branching fraction ℬ[𝜓(3686)→𝛾𝜂𝑐(2𝑆)]×ℬ[𝜂𝑐(2𝑆)→3(𝜋+𝜋−)] is measured to be (9.2±1.0 (stat)±1.2 (syst))×10−6. Using ℬ[𝜓(3686)→𝛾𝜂𝑐(2𝑆)]=(7.0+3.4−2.5)×10−4, we obtain ℬ[𝜂𝑐(2𝑆)→3(𝜋+𝜋−)]=(1.31±0.15 (stat)±0.17 (syst) (+0.64−0.47) (extr))×10−2, where the third uncertainty is from ℬ[𝜓(3686)→𝛾𝜂𝑐(2𝑆)]. We also measure the 𝜒𝑐𝐽→3(𝜋+𝜋−) (𝐽=0, 1, 2) decays via 𝜓′→𝛾𝜒𝑐𝐽 transitions. The branching fractions are ℬ[𝜒𝑐0→3(𝜋+𝜋−)]=(2.080±0.006 (stat)±0.068 (syst))×10−2, ℬ[𝜒𝑐1→3(𝜋+𝜋−)]=(1.092±0.004 (stat)±0.035 (syst))×10−2, and ℬ[𝜒𝑐2→3(𝜋+𝜋−)]=(1.565±0.005 (stat)±0.048 (syst))×10−2.
Observation of ηc(2S) → 3(π⁺π⁻) and measurements of χcJ → 3(π⁺π⁻) in ψ(3686) radiative transitions
(2022)
The hadronic decay ηc(2S)→3(π+π−) is observed with a statistical significance of 9.3 standard deviations using (448.1±2.9)×106 ψ(3686) events collected by the BESIII detector at the BEPCII collider. The measured mass and width of ηc(2S) are (3643.4±2.3(stat.)±4.4(syst.)) MeV/c2 and (19.8±3.9(stat.)±3.1(syst.)) MeV, respectively, which are consistent with the world average values within two standard deviations. The product branching fraction B[ψ(3686)→γηc(2S)]×B[ηc(2S)→3(π+π−)] is measured to be (9.2±1.0(stat.)±0.9(syst.))×10−6. Using B[ψ(3686)→γηc(2S)]=(7.0+3.4−2.5)×10−4, we obtain B[ηc(2S)→3(π+π−)]=(1.31±0.15(stat.)±0.13(syst.)(+0.64−0.47)(extr))×10−2, where the third uncertainty is from B[ψ(3686)→γηc(2S)]. We also measure the χcJ→3(π+π−) (J=0,1,2) decays via ψ(3686)→γχcJ transitions. The branching fractions are B[χc0→3(π+π−)]=(2.080±0.006(stat.)±0.068(syst.))×10−2, B[χc1→3(π+π−)]=(1.092±0.004(stat.)±0.035(syst.))×10−2, and B[χc2→3(π+π−)]=(1.565±0.005(stat.)±0.048(syst.))×10−2.
Observation of ηc(2S) → 3(π⁺π⁻) and measurements of χcJ → 3(π⁺π⁻) in ψ(3686) radiative transitions
(2022)
The hadronic decay ηc(2S)→3(π+π−) is observed with a statistical significance of 9.3 standard deviations using (448.1±2.9)×106 ψ(3686) events collected by the BESIII detector at the BEPCII collider. The measured mass and width of ηc(2S) are (3643.4±2.3(stat.)±4.4(syst.)) MeV/c2 and (19.8±3.9(stat.)±3.1(syst.)) MeV, respectively, which are consistent with the world average values within two standard deviations. The product branching fraction B[ψ(3686) → γηc(2S)]×B[ηc(2S)→3(π+π−)] is measured to be (9.2±1.0(stat.)±0.9(syst.))×10−6. Using B[ψ(3686)→γηc(2S)]=(7.0+3.4−2.5)×10−4, we obtain B[ηc(2S)→3(π+π−)]=(1.31±0.15(stat.)±0.13(syst.)(+0.64−0.47)(extr))×10−2, where the third uncertainty is from B[ψ(3686)→γηc(2S)]. We also measure the χcJ→3(π+π−) (J=0,1,2) decays via ψ(3686)→γχcJ transitions. The branching fractions are B[χc0→3(π+π−)]=(2.080±0.006(stat.)±0.068(syst.))×10−2, B[χc1→3(π+π−)]=(1.092±0.004(stat.)±0.035(syst.))×10−2, and B[χc2→3(π+π−)]=(1.565±0.005(stat.)±0.048(syst.))×10−2.
In Deutschland leidet ca. jeder zehnte Mensch über 40 Jahren an einer chronischen Einschränkung seiner Nierenfunktion. Nicht wenige davon sind im Laufe der Erkrankung auf eine Nierenersatztherapie angewiesen. Die Ursachen für eine Nierenschädigung sind vielfältig. Als neuartiger und vielversprechender Therapieansatz werden aktuell Mesenchymale Stamm-/Stromazellen (MSC) als Therapeutikum für diverse Nierenerkrankungen getestet. Erste Ergebnisse klinischer Phase-I-Studien zeigen, dass MSC sicher als Immunsuppressivum nach Nierentransplantation angewendet werden können. Auch für weitere Erkrankungen der Niere sind erste klinische Studien am Laufen. MSC gelten als regenerativ, immunsupprimierend und antientzündlich. Dennoch gibt es noch einige Limitationen. Nach der Transplantation der Zellen ist das Wachstum der Zellen oft eingeschränkt und es kommt zur vermehrten Apoptose. Auch wird immer wieder ein paradoxes und entzündungsförderndes Verhalten der MSC am Wirkort beobachtet. Ein wichtiger Lösungsansatz ist eine in vitro Vorbehandlung der MSC zur Modulierung der zellulären Eigenschaften. In dieser Arbeit wurden drei Substanzen und Arzneimittel auf ihre Fähigkeit untersucht, die entzündungshemmenden Eigenschaften der MSC zu verbessern und die entzündungsfördernden zu unterdrücken. Der Fokus lag hierbei auf dem Arzneimittel Niclosamid und den beiden bisher noch nicht zugelassenen Substanzen Berberin und Gedunin, die alle in vitro und in vivo bereits erste vielversprechende antientzündliche Wirkungen bewiesen haben. Für diese Arbeit wurden MSC aus Fettgewebe isoliert (ASC) und mit LPS oder einem Cytokin-Mix (Mischung aus TNF-α, IFN-γ und IL-1β) sowie den drei Substanzen stimuliert. Untersucht wurden im Anschluss die mRNA-Expressionen der gängigsten proinflammatorischen (TNF-α, IL-6, TLR-4, ICAM-1, HLA-DR) und antiinflammatorischen Marker (IDO, IL-10), sowie mittels ELISA die Protein-Freisetzung von IL-6 und IL-8. Die vielversprechendsten Ergebnisse ließen sich durch Berberin hervorrufen. Hier zeigte sich eine deutliche Senkung der IL-8-Konzentration im ELISA. Die Anwendung des Gedunin hatte keine signifikante Wirkung auf die ASC. Niclosamid hingegen scheint widererwarten sogar entzündungsfördernd zu wirken, in dem es die IL-6-, ICAM-1-mRNA-Expression steigerte und die IDO-mRNA-Expression absenkte. Unter den drei getesteten Subtanzen hat Berberin die beste Wirkung bewiesen. Nach weiterer Testung könnte eine Anwendung mit Berberin als in vitro Präkonditionierung von MSC vielversprechend sein. Die Verwendung von Niclosamid hingegen sollte vermieden werden, die Wirkung von Gedunin müsste genauer untersucht werden.
The absolute branching fraction of the decay Λc(2625)+→Λ+cπ+π− is measured for the first time to be (50.7±5.0stat.±4.9syst.)% with 368.48 pb−1 of e+e− collision data collected by the BESIII detector at the center-of-mass energies of s√=4.918 and 4.950 GeV. This result is lower than the naive prediction of 67\%, obtained from isospin symmetry, by more than 2σ, thereby indicating that the novel mechanism referred to as the \textit{threshold effect}, proposed for the strong decays of Λc(2595)+, also applies to Λc(2625)+. This measurement is necessary to obtain the coupling constants for the transitions between s-wave and p-wave charmed baryons in heavy hadron chiral perturbation theory. In addition, we search for the decay Λc(2595)+→Λ+cπ+π−. No significant signal is observed, and the upper limit on its branching fraction is determined to be 80.8\% at the 90\% confidence level.
We report new STAR measurements of the single-spin asymmetries 𝐴𝐿 for 𝑊+ and 𝑊− bosons produced in polarized proton-proton collisions at √𝑠=510 GeV as a function of the decay-positron and decay-electron pseudorapidity. The data were obtained in 2013 and correspond to an integrated luminosity of 250 pb−1. The results are combined with previous results obtained with 86 pb−1. A comparison with theoretical expectations based on polarized lepton-nucleon deep-inelastic scattering and prior polarized proton-proton data suggests a difference between the ¯𝑢 and ¯𝑑 quark helicity distributions for 0.05<𝑥<0.25. In addition, we report new results for the double-spin asymmetries 𝐴𝐿𝐿 for 𝑊±, as well as 𝐴𝐿 for 𝑍/𝛾* production and subsequent decay into electron-positron pairs.
Using a sample of (10.09 ± 0.04) × 109 J/ψ decays collected with the BESIII detector, partial wave analyses of the decay J/ψ → γK0SK0Sπ0 are performed within the K0SK0Sπ0 invariant mass region below 1.6 GeV/c2. The covariant tensor amplitude method is used in both mass independent and mass dependent approaches. Both analysis approaches exhibit dominant pseudoscalar and axial vector components, and show good consistency for the other individual components. Furthermore, the mass dependent analysis reveals that the K0SK0 Sπ0 invariant mass spectrum for the pseudoscalar component can be well described with two isoscalar resonant states using relativistic Breit-Wigner model, i.e., the η(1405) with a mass of 1391.7±0.7+11.3 −0.3 MeV/c 2 and a width of 60.8±1.2+5.5 −12.0 MeV, and the η(1475) with a mass of 1507.6±1.6+15.5−32.2 MeV/c2 and a width of 115.8±2.4 +14.8 −10.9 MeV. The first and second uncertainties are statistical and systematic, respectively. Alternate models for the pseudoscalar component are also tested, but the description of the K0SK0Sπ0invariant mass spectrum deteriorates significantly.
We report a measurement of the cross section for the process e+e−→π+π−J/ψ around the X(3872) mass in search for the direct formation of e+e−→X(3872) through the two-photon fusion process. No enhancement of the cross section is observed at the X(3872) peak and an upper limit on the product of electronic width and branching fraction of X(3872)→π+π−J/ψ is determined to be Γee×B(X(3872)→π+π−J/ψ)<7.5×10−3eV at 90% confidence level under an assumption of total width of 1.19±0.21 MeV. This is an improvement of a factor of about 17 compared to the previous limit. Furthermore, using the latest result of B(X(3872)→π+π−J/ψ), an upper limit on the electronic width Γee of X(3872) is obtained to be <0.32eV at the 90% confidence level.
A measurement of the CP-even fraction of the decay D0→π+π−π+π− is performed with a quantum-correlated ψ(3770)→DD¯ data sample collected by the BESIII experiment, corresponding to an integrated luminosity of 2.93 fb−1. Using a combination of CP eigenstates, D→π+π−π0 and D→K0S,Lπ+π− as tagging modes, the CP-even fraction is measured to be F4π+=0.735±0.015±0.005, where the first uncertainty is statistical and the second is systematic. This is the most precise determination of this quantity to date. It provides valuable model-independent input for the measurement of the CKM angle γ with B±→DK± decays, and for time-dependent studies of CP violation and mixing in the D0-D¯0 system.
A measurement of the 𝐶𝑃-even fraction of the decay 𝐷0→𝜋+𝜋−𝜋+𝜋− is performed with a quantum-correlated 𝜓(3770)→𝐷¯𝐷 data sample collected by the BESIII experiment, corresponding to an integrated luminosity of 2.93 fb−1. Using a combination of 𝐶𝑃 eigenstates, 𝐷→𝜋+𝜋−𝜋0 and 𝐷→𝐾0𝑆,𝐿𝜋+𝜋− as tagging modes, the 𝐶𝑃-even fraction is measured to be 𝐹4𝜋+=0.735±0.015±0.005, where the first uncertainty is statistical and the second is systematic. This is the most precise determination of this quantity to date. It provides valuable model-independent input for the measurement of the angle 𝛾 of the Cabibbo-Kobayashi-Maskawa matrix with 𝐵±→𝐷𝐾± decays, and for time-dependent studies of 𝐶𝑃 violation and mixing in the 𝐷0−¯𝐷0 system.
Using a data sample of (448.1±2.9)×106 𝜓(3686) decays collected at an 𝑒+𝑒− center-of-mass energy of 3.686 GeV by the BESIII detector at Beijing Electron Positron Collider II, we report an observation of the hindered electromagnetic Dalitz decay 𝜓(3686)→𝑒+𝑒−𝜂𝑐 with a significance of 7.9𝜎. The branching fraction is determined to be ℬ(𝜓(3686)→𝑒+𝑒−𝜂𝑐)=(3.77±0.40stat±0.18syst)×10−5, agreeing well with the prediction of the vector meson dominance model. This is the first measurement of the electromagnetic Dalitz transition between the 𝜓(3686) and the 𝜂𝑐, which provides new insight into the electromagnetic properties of this decay, and offers new opportunities to measure the absolute branching fractions of 𝜂𝑐 decays.
Das Schilddrüsenkarzinom (SK) ist die häufigste bösartige endokrine Tumorerkrankung. Während das nicht-metastasierte und nicht-mutierte papilläre Schilddrüsenkarzinom (PSK) und das follikuläre Schilddrüsenkarzinom (FSK) eine gute Heilungschance aufweisen, zeigen die mutierten und metastasierten Varianten des PSK und FSK sowie das anaplastische Schilddrüsenkarzinom (ASK) weiterhin eine schlechte Prognose. Die Entwicklung von Therapieresistenzen stellen hierbei ein Hauptproblem in der Behandlung des fortgeschrittenen Schilddrüsenkarzinoms dar.
In den letzten Jahren wurden in Studien zunehmend Tumor-initiierende Zellen (TIZ) beschrieben, welche eine kleine Subpopulation von Zellen mit der Fähigkeit zur Selbsterneuerung, Tumorinitiierung und Entwicklung von Therapieresistenzen von Tumoren darstellen. Die Existenz von TIZ wurde auch im SK nachgewiesen. Ein entscheidender Faktor für die Persistenz von TIZ ist die Hypoxie, welche über eine Veränderung des Tumormikromilieus und des Zellmetabolismus zur Entstehung von Therapieresistenzen beiträgt. Ein durch Hypoxie hochreguliertes Enzym ist die Carboanhydrase IX (CAIX). CAIX wird hauptsächlich von Tumorzellen exprimiert und katalysiert die Reaktion von Kohlendioxid zu Bicarbonat und einem Proton und trägt damit zur Säurepufferung der Tumorzelle bei. CAIX stellt somit einen entscheidenden Faktor für das Überleben von Tumorzellen in einem hypoxischen Milieu dar. Des Weiteren ist eine erhöhte Expression von CAIX mit einem schlechten Patienten-Outcome assoziiert, wie z.B. im Brustkrebs. Diese Eigenschaften machen CAIX zu einem attraktiven Angriffspunkt einer zielgerichteten Tumortherapie. Die vorliegende Studie hat zum Ziel, die Expression von CAIX sowie dessen biologische Rolle im Schilddrüsenkarzinom näher zu untersuchen.
Hierzu wurden Proben von 114 SK-Patienten immunhistochemisch auf eine CAIX-Expression untersucht und mit tumorfreiem Schilddrüsengewebe verglichen. Hierbei waren unterschiedliche SK-Subtypen vertreten. Für eine weitere Validierung der Expressionsdaten erfolgte die Auswertung eines Datasets von „The Cancer Genome Atlas“ (TCGA) mithilfe von cBioportal. Da die Hypoxie ein wichtiger Faktor für die Persistenz von TIZ ist, wurde die CAIX-Expression in Tumorsphären, ein in vitro Nachweis von TIZ-Aktivität, mittels der Durchflusszytometrie bestimmt und mit der CAIX-Expression von Monolayern verglichen. Als SK-Zelllinien wurden BCPAP (PSK), FTC 133 (FSK) und 8505 C (ASK) verwendet. Anschließend wurde mithilfe der Polymerasekettenreaktion und Immunofluoreszenzfärbung untersucht, ob eine CAIX-Expression in den Tumorsphären mit der Expression von bereits bekannten Stammzellmarkern, u.a. NANOG, assoziiert ist. Die Unterschiede der CAIX-Expression, nach Inkubation der Monolayer jeweils in Normoxie und Hypoxie, wurden mittels Durchflusszytometrie bestimmt. Mithilfe eines genetischen CAIX-Knockdowns sowie einer pharmakologischen Inhibition mit dem CAIX-Inhibitor Methazolamid (MZM) wurde die Tumorzellproliferation und -Sphärenbildung unter Normoxie und Hypoxie bestimmt. Zusätzlich wurde der Einfluss von MZM auf die Apoptose und den Zellzyklus untersucht.
Immunhistochemische Färbungen der Gewebeproben von SK-Patienten zeigten, dass die CAIX-Expression sowohl im PSK und FSK als auch im ASK im Vergleich zum tumorfreien Schilddrüsengewebe erhöht war. Des Weiteren zeigte die klinisch-pathologische Datenanalyse, dass eine erhöhte CAIX-Expression mit dem Auftreten von Lymphknotenmetastasen im differenzierten SK assoziiert war. Auch die Analyse des TCGA-Datasets bestätigte, dass eine erhöhte Expression der CAIX-mRNA mit einem fortgeschrittenen Tumorstadium, Fernmetastasen und mit einem kürzeren Gesamt-Überleben von SK-Patienten korrelierte. Die weiteren funktionellen in vitro Untersuchungen ergaben, dass die CAIX-Expression in den Tumorsphären im Vergleich zu Monolayern erhöht und mit einer erhöhten Expression von Stammzellmarkern assoziiert war. Ein genetischer CAIX-Knockdown und eine CAIX-Inhibition mit MZM führten über eine Induktion der Apoptose und eines Zellzyklusarrests zu einer verminderten Tumorzellproliferation und Sphärenbildung.
Zusammenfassend deuten die Ergebnisse darauf hin, dass CAIX ein vielversprechendes Zielmolekül für eine gezielte Tumortherapie des fortgeschrittenen SK ist. Um diese Hypothese bestätigen zu können, sind jedoch weitere prospektive Analysen von Patientenproben sowie funktionelle in vivo Untersuchungen am SK nötig.
Dynamic imaging of landmark organelles, such as nuclei, cell membrane, nuclear envelope, and lipid droplets enables image-based phenotyping of functional states of cells. Multispectral fluorescent imaging of landmark organelles requires labor-intensive labeling, limits throughput, and compromises cell health. Virtual staining of label-free images with deep neural networks is an emerging solution for this problem. Multiplexed imaging of cellular landmarks from scattered light and subsequent demultiplexing with virtual staining saves the light spectrum for imaging additional molecular reporters, photomanipulation, or other tasks. Published approaches for virtual staining of landmark organelles are fragile in the presence of nuisance variations in imaging, culture conditions, and cell types. This paper reports model training protocols for virtual staining of nuclei and membranes robust to label-free imaging parameters, cell states, and cell types. We developed a flexible and scalable convolutional architecture, named UNeXt2, for supervised training and self-supervised pre-training. The strategies we report here enable robust virtual staining of nuclei and cell membranes in multiple cell types, including neuromasts of zebrafish, across a range of imaging conditions. We assess the models by comparing the intensity, segmentations, and application-specific measurements obtained from virtually stained and experimentally stained nuclei and membranes. The models rescue the missing label, non-uniform expression of labels, and photobleaching. We share three pre-trained models, named VSCyto3D, VSCyto2D, and VSNeuromast, as well as VisCy, a PyTorch-based pipeline for training, inference, and deployment that leverages the modern OME-Zarr format.
Lattice QCD investigation of a doubly-bottom b̄b̄ud tetraquark with quantum numbers I(JP) = 0(1⁺)
(2019)
We use lattice QCD to investigate the spectrum of the ¯𝑏¯𝑏𝑢𝑑 four-quark system with quantum numbers 𝐼(𝐽𝑃)=0(1+). We use five different gauge-link ensembles with 2+1 flavors of domain-wall fermions, including one at the physical pion mass, and treat the heavy ¯𝑏 quark within the framework of lattice nonrelativistic QCD. Our work improves upon previous similar computations by considering in addition to local four-quark interpolators also nonlocal two-meson interpolators and by performing a Lüscher analysis to extrapolate our results to infinite volume. We obtain a binding energy of (−128±24±10) MeV, corresponding to the mass (10476±24±10) MeV, which confirms the existence of a ¯𝑏¯𝑏𝑢𝑑 tetraquark that is stable with respect to the strong and electromagnetic interactions.
We present our recent results on antiheavy-antiheavy-light-light tetraquark systems using lattice QCD. Our study of the b¯b¯us four-quark system with quantum numbers JP=1+ and the b¯c¯ud four-quark systems with I(JP)=0(0+) and I(JP)=0(1+) utilizes scattering operators at the sink to improve the extraction of the low-lying energy levels. We found a bound state for b¯b¯us with Ebind,b¯b¯us=(−86±22±10)MeV, but no indication for a bound state in both b¯c¯ud channels. Moreover, we show preliminary results for b¯b¯ud with I(JP)=0(1+), where we used scattering operators both at the sink and the source. We found a bound state and determined its infinite-volume binding energy with a scattering analysis, resulting in Ebind,b¯b¯ud=(−103±8)MeV.
The rare decay 𝜂′→𝜋+𝜋−𝑒+𝑒− is studied using a sample of 1.3×109 𝐽/𝜓 events collected with the BESIII detector at BEPCII in 2009 and 2012. The branching fraction is measured with improved precision to be (2.42±0.05stat±0.08syst)×10−3. Due to the inclusion of new data, this result supersedes the last BESIII result on this branching fraction. In addition, the 𝐶𝑃-violating asymmetry in the angle between the decay planes of the 𝜋+𝜋−-pair and the 𝑒+𝑒−-pair is investigated. A measurable value would indicate physics beyond the standard model; the result is 𝒜𝐶𝑃=(2.9±3.7stat±1.1syst)%, which is consistent with the standard model expectation of no 𝐶𝑃-violation. The precision is comparable to the asymmetry measurement in the 𝐾0𝐿→𝜋+𝜋−𝑒+𝑒− decay where the observed (14±2)% effect is driven by a standard model mechanism.
Einleitung: Die Zentrale Notaufnahme (ZNA) stellt eine Schnittstelle zwischen prä- und innerklinischer Versorgung dar. Das Spektrum der Krankheitsbilder erstreckt sich über jegliche Fachrichtungen und variiert von harmlosen Banalitäten bis zu akuten Notfällen. Eine sichere und suffiziente Primärversorgung ist die Basis eines qualitativ-hochwertigen Gesundheitssystems.2 Verspätete oder falsche Diagnosen in der ZNA sind mit 10-30 % keine Seltenheit.
Dies ist nicht nur für den individuellen Patienten belastend, es bedeutet auch einen zusätzlichen Ressourcenverbrauch und eine finanzielle Belastung für das Gesundheitssystem. Clinical Decision Support Systems (CDSS) haben das Potenzial, sowohl professionelle Anwender als auch Laien bei ihrer Diagnosefindung zu unterstützen. Fragestellung: Ziel der Arbeit ist es herauszufinden, welchen Einfluss der Diagnosezeitpunkt auf das Outcome von Patienten mit Abdominalschmerzen in der ZNA hat und inwiefern ein CDSS das Potenzial hat, die genannten Punkte zu beeinflussen.
Methoden: Es handelte sich um eine prospektive, doppelt verblindete Beobachtungsstudie. Patienten, die sich mit Abdominalschmerzen in der Notaufnahme vorstellten, gaben ihre Symptome in die Ada-App ein. Sowohl die Diagnosevorschläge der App als auch die Verdachtsdiagnosen des behandelnden Arztes wurden dokumentiert und verglichen. Weitere erhobene Parameter waren die Verwendung von apparativer Diagnostik, die vergangene Zeit bis zur endgültigen Diagnosestellung, das Auftreten von Komplikationen, die Komorbidität und Mortalität sowie die Länge des Krankenhausaufenthalts. Das Follow-Up erfolgte zu verschiedenen Zeitpunkten bis zu Tag 90. Für die Analyse wurden die 450 Patienten anhand des Zeitpunkts ihrer Diagnosestellung in Gruppen "früh" (Tag 0) und "spät" (Tag 1-24) eingeteilt.
Ergebnisse: Im Vergleich zur „frühen“ Gruppe, hatte die Gruppe der „spät“ diagnostizierten Patienten einen höheren Anteil von Männern (45.2% (n=168/372) versus 60.3 % (n=47/78); p=0.018), im Schnitt einen höheren Charlson Comorbidity Index (0.7 versus 1.1; p=0.045) und im Schnitt einen höheren RAI-C Score (8.06 versus 9.9; p<0.001) am Tag ihrer Vorstellung. Bei den „spät“ diagnostizierten blieben weniger Patienten komplikationsfrei (57.0 % 49 (n=212/372) versus 17.9% (n=14/78); p<0.001), es traten mehr Major-Komplikationen auf (8.9% (n=33/372) versus 17.9% (n=14/78); p=0.024), analog dazu war der Comprehensive Complication Index höher (13.1 versus 25.6; p<0.001) und sie verweilten länger im Krankenhaus (2.6 Tage versus 6.7 Tage; p<0.001). Zudem nahmen sie signifikant mehr apparative Diagnostik in Anspruch.
Die behandelnden Ärzte konnten in 82.6% der Fälle (n=372/450) am Tag der Vorstellung die korrekte Diagnose stellen. Die Ada-App konnte in insgesamt 52% der Fälle (n=234/450) die korrekte Diagnose unter ihren Diagnoseverschlägen nennen.
Schlussfolgerung: Multimorbide Patienten scheinen anfälliger zu sein für falsche und verspätete Diagnosen. Ein später Diagnosezeitpunkt korreliert mit der vermehrten Nutzung apparativer Diagnostik, einem komplikationsreicheren Verlauf, einer höheren Komorbidität und einem längeren Krankenhausaufenthalt.
Die Ada-App ist den Ärzten zwar unterlegen, dennoch ist Potenzial vorhanden.
Für Ärzte kann die Ada-App eine Unterstützung im Rahmen der Diagnosefindung darstellen. Neben der Ressourcenentlastung kann sie vor Fehlannahmen und frühzeitigen Schlussfolgerungen schützen und auf weitere mögliche Differentialdiagnosen hinweisen. Die Ada-App stellt für Laien mit Sicherheit eine Weiterentwicklung gegenüber der simplen Symptomsuche über das Internet dar, dennoch sollten weitere Studien den Nutzen und die Sicherheit der App überprüfen.
Search for the reaction channel e⁺e⁻ → ηcηπ⁺π⁻ at center-of-mass energies from 4.23 to 4.60 GeV
(2021)
Using data collected with the BESIII detector operating at the Beijing Electron Positron Collider, we search for the process 𝑒+𝑒−→𝜂𝑐𝜂𝜋+𝜋−. The search is performed using five large datasets recorded at center-of-mass energies of 4.23, 4.26, 4.36, 4.42, and 4.60 GeV. The 𝜂𝑐 meson is reconstructed in 16 exclusive decay modes. No signal is observed in the 𝜂𝑐 mass region at any center-of-mass energy. The upper limits on the reaction cross sections are determined to be 6.2, 10.8, 27.6, 22.6 and 23.7 pb at the 90% confidence level at the center-of-mass energies listed above.
Using a sample of 1.31×109 𝐽/𝜓 events collected with the BESIII detector, we perform a study of 𝐽/𝜓→𝛾𝜂𝜂𝜂′ to search for the 𝑋(2370) and 𝜂𝑐 in the 𝜂𝜂𝜂′ invariant mass distribution. No significant signal for the 𝑋(2370) is observed, and we set an upper limit for the product branching fraction of ℬ(𝐽/𝜓→𝛾𝑋(2370)·ℬ(𝑋(2370)→𝜂𝜂𝜂′)<9.2×10−6 at the 90% confidence level. A clear 𝜂𝑐 signal is observed for the first time, yielding a product branching fraction of ℬ(𝐽/𝜓→𝛾𝜂𝑐)·ℬ(𝜂𝑐→𝜂𝜂𝜂′)=(4.86±0.62(stat)±0.45(sys))×10−5.
Observation of η′ → π⁺π⁻μ⁺μ⁻
(2021)
Using (1310.6±7.0)×106 𝐽/𝜓 events acquired with the BESIII detector at the BEPCII storage rings, the decay 𝜂′→𝜋+𝜋−𝜇+𝜇− is observed for the first time with a significance of 8𝜎 via the process 𝐽/𝜓→𝛾𝜂′. We measure the branching fraction of 𝜂′→𝜋+𝜋−𝜇+𝜇− to be ℬ(𝜂′→𝜋+𝜋−𝜇+𝜇−)=(1.97±0.33(stat)±0.19(syst))×10−5, where the first and second uncertainties are statistical and systematic, respectively
he Born cross sections for the process 𝑒+𝑒−→𝜂′𝜋+𝜋− at different center-of-mass energies between 2.00 and 3.08 GeV are reported with improved precision from an analysis of data samples collected with the BESIII detector operating at the BEPCII storage ring. An obvious structure is observed in the Born cross section line shape. Fit as a Breit-Wigner resonance, it has a statistical significance of 6.3𝜎 and a mass and width of 𝑀=(2111±43±25) MeV/𝑐2 and Γ=(135±34±30) MeV, where the uncertainties are statistical and systematic, respectively. These measured resonance parameters agree with the measurements of BABAR in 𝑒+𝑒−→𝜂′𝜋+𝜋− and BESIII in 𝑒+𝑒−→𝜔𝜋0 within two standard deviations.
The Born cross sections for the process e+e−→η′π+π− at different center-of-mass energies between 2.00 and 3.08 GeV are reported with improved precision from an analysis of data samples collected with the BESIII detector operating at the BEPCII storage ring. An obvious structure is observed in the Born cross section line shape. Fit as a Breit-Wigner resonance, it has a statistical significance of 6.3σ and a mass and width of M=(2111±43±25)~MeV/c2 and Γ=(135±34±30)~MeV, where the uncertainties are statistical and systematic, respectively. These measured resonance parameters agree with the measurements of BABAR in e+e−→η′π+π− and BESIII in e+e−→ωπ0 within two standard deviations.
The Born cross sections for the process e+e−→η′π+π− at different center-of-mass energies between 2.00 and 3.08~GeV are reported with improved precision from an analysis of data samples collected with the BESIII detector operating at the BEPCII storage ring. An obvious structure is observed in the Born cross section line shape. Fit as a Breit-Wigner resonance, it has a statistical significance of 6.3σ and a mass and width of M=(2108±46±25)~MeV/c2 and Γ=(138±36±30)~MeV, where the uncertainties are statistical and systematic, respectively. These measured resonance parameters agree with the measurements of BABAR in e+e−→η′π+π− and BESIII in e+e−→ωπ0 within two standard deviations.
Finanzielle Armut prägt Mobilitätspraktiken und kann dabei zum Prozess von mobilitätsbezogener sozialer Exklusion beitragen. Zu den Personen, deren Armutsrisiko besonders hoch ist, zählen in Deutschland Haushalte mit Kindern, insbesondere Alleinerziehende. Ältere Menschen haben nicht die höchste Armutsgefährdung, jedoch besteht bei ihnen das Risiko von Verharrung in Armut, da die Möglichkeiten, die finanzielle Situation aus eigener Kraft zu ändern mit zunehmendem Alter sinken.
Um ein tieferes Verständnis davon zu erhalten, wie finanzielle Armut die Mobilitätspraktiken und soziale Teilhabe von Haushalten mit Kindern sowie älteren Menschen prägt, wurden mit diesen beiden Personengruppen problemzentrierte Interviews in Ronnenberg (Region Hannover) geführt und analysiert. Die Ergebnisse belegen, dass, wenngleich alle Befragten mit ähnlich geringen finanziellen Ressourcen haushalten und Verzicht sowie Abwägungsprozesse notwendig sind, sich ihre Mobilitätspraktiken und Alltagsbewältigungsstrategien unterscheiden, was sich in zwei Typologien widerspiegelt. Erstens, eine Typologie der Mobilitätspraktiken von Haushalten mit Kindern: (i) autozentriert, (ii) autoreduziert, (iii) ÖPNV-orientiert und (iv) nichtmotorisiert. Zweitens, eine Typologie älterer Menschen anhand ihrer Mobilitätspraktiken: (i) aktive ältere Menschen mit vielseitigen sozialen Interaktionen, (ii) nachbarschaftsorientierte ältere Menschen mit lokalen Kontakten und (iii) ältere Menschen, die überwiegend zu Hause sind und wenig soziale Kontakte haben.
Um herauszufinden, inwiefern mobilitätsbezogene Barrieren der sozialen Teilhabe reduziert werden können, wurden fünf Maßnahmen bezüglich ihrer Wirkung auf die Mobilitätspraktiken einkommensarmer Haushalte mit Kindern untersucht: einerseits die Wirkung des 9-Euro-Tickets anhand von problemzentrierten Interviews mit einkommensarmen Haushalten mit Kindern, andererseits anhand von Expert:inneninterviews die Wirkung von Radlernkursen für Frauen mit Migrationshintergrund, eines Mietertickets, eines Quartierstickets und der Verbesserung der Nahraum- und Aufenthaltsqualität am Beispiel von Tempo 30. Die Ergebnisse zum 9-Euro-Ticket belegen, dass ein erschwingliches ÖPNV-Ticket erheblich zur Reduzierung mobilitätsbezogener Barrieren der sozialen Teilhabe im Armutskontext beiträgt. Die Expert:inneninterviews zeigen auf, dass eine Förderung des Umweltverbunds zielführend ist, um zu einer sozial-ökologischen Verkehrswende beizutragen und insbesondere Maßnahmenbündel Wirkung auf die Reduzierung von mobilitätsbezogenen Barrieren der sozialen Teilhabe entfalten.
Die Erkenntnisse dieser Dissertation ergänzen den wissenschaftlichen Forschungstand um ein tiefergehendes Verständnis der Wirkung von finanzieller Armut auf die Mobilitätspraktiken und soziale Teilhabe von Haushalten mit Kindern und älteren Menschen und helfen dabei, Maßnahmen zur Reduzierung mobilitätsbezogener Barrieren der sozialen Teilhabe zu konzipieren und umzusetzen.
The Born cross sections for the process e+e−→η′π+π− at different center-of-mass energies between 2.00 and 3.08~GeV are reported with improved precision from an analysis of data samples collected with the BESIII detector operating at the BEPCII storage ring. An obvious structure is observed in the Born cross section line shape. Fit as a Breit-Wigner resonance, it has a statistical significance of 6.3σ and a mass and width of M=(2108±46±25)~MeV/c2 and Γ=(138±36±30)~MeV, where the uncertainties are statistical and systematic, respectively. These measured resonance parameters agree with the measurements of BABAR in e+e−→η′π+π− and BESIII in e+e−→ωπ0 within two standard deviations.
We report a study of the processes of e+e−→K+(D−sD∗0+D∗−sD0) based on e+e− annihilation samples collected with the BESIII detector operating at BEPCII at five center-of-mass energies ranging from 4.628 to 4.698 GeV with a total integrated luminosity of 3.7 fb−1. An excess over the known contributions of the conventional charmed mesons is observed near the D−sD∗0 and D∗−sD0 mass thresholds in the K+ recoil-mass spectrum for events collected at s√=4.681 GeV. The structure matches a mass-dependent-width Breit-Wigner line shape, whose pole mass and width are determined as (3982.5+1.8−2.6±2.1) MeV/c2 and (12.8+5.3−4.4±3.0) MeV, respectively. The first uncertainties are statistical and the second are systematic. The significance of the resonance hypothesis is estimated to be 5.3 σ over the contributions only from the conventional charmed mesons. This is the first candidate of the charged hidden-charm tetraquark with strangeness, decaying into D−sD∗0 and D∗−sD0. However, the properties of the excess need further exploration with more statistics.
We report a study of the processes of e+e−→K+(D−sD∗0+D∗−sD0) based on e+e− annihilation samples collected with the BESIII detector operating at BEPCII at five center-of-mass energies ranging from 4.628 to 4.698 GeV with a total integrated luminosity of 3.7 fb−1. An excess over the known contributions of the conventional charmed mesons is observed near the D−sD∗0 and D∗−sD0 mass thresholds in the K+ recoil-mass spectrum for events collected at s√=4.681 GeV. The structure matches a mass-dependent-width Breit-Wigner line shape, whose pole mass and width are determined as (3982.5+1.8−2.6±2.1) MeV/c2 and (12.8+5.3−4.4±3.0) MeV, respectively. The first uncertainties are statistical and the second are systematic. The significance of the resonance hypothesis is estimated to be 5.3 σ over the pure contributions from the conventional charmed mesons. This is the first candidate of the charged hidden-charm tetraquark with strangeness, decaying into D−sD∗0 and D∗−sD0. However, the genuine properties of the excess need further exploration with more statistics.
Observation of a near-threshold structure in the K⁺ recoil-mass spectra in e⁺e⁻ → K⁺(Dₛ⁻D*⁰+Dₛ*⁻D⁰)
(2021)
We report a study of the processes of 𝑒+𝑒−→𝐾+𝐷−𝑠𝐷*0 and 𝐾+𝐷*−𝑠𝐷0 based on 𝑒+𝑒− annihilation samples collected with the BESIII detector operating at BEPCII at five center-of-mass energies ranging from 4.628 to 4.698 GeV with a total integrated luminosity of 3.7 fb−1. An excess of events over the known contributions of the conventional charmed mesons is observed near the 𝐷−𝑠𝐷*0 and 𝐷*−𝑠𝐷0 mass thresholds in the 𝐾+ recoil-mass spectrum for events collected at √𝑠=4.681 GeV. The structure matches a mass-dependent-width Breit-Wigner line shape, whose pole mass and width are determined as (3982.5+1.8
−2.6±2.1) MeV/𝑐2 and (12.8+5.3−4.4±3.0) MeV, respectively. The first uncertainties are statistical and the second are systematic. The significance of the resonance hypothesis is estimated to be 5.3 𝜎 over the contributions only from the conventional charmed mesons. This is the first candidate for a charged hidden-charm tetraquark with strangeness, decaying into 𝐷−𝑠𝐷*0 and 𝐷*−𝑠𝐷0. However, the properties of the excess need further exploration with more statistics.
In this work we investigate the existence of bound states for doubly heavy tetraquark systems Q¯Q¯′qq′ in a full lattice-QCD computation, where heavy bottom quarks are treated in the framework of non-relativistic QCD. We focus on three systems with quark content b¯b¯ud, b¯b¯us and b¯c¯ud. We show evidence for the existence of b¯b¯ud and b¯b¯us bound states, while no binding appears to be present for b¯c¯ud. For the bound four-quark states we also discuss the importance of various creation operators and give an estimate of the meson-meson and diquark-antidiquark percentages.
In this work we investigate the existence of bound states for doubly heavy tetraquark systems Q¯Q¯′qq′ in a full lattice-QCD computation, where heavy bottom quarks are treated in the framework of non-relativistic QCD. We focus on three systems with quark content b¯b¯ud, b¯b¯us and b¯c¯ud. We show evidence for the existence of b¯b¯ud and b¯b¯us bound states, while no binding appears to be present for b¯c¯ud. For the bound four-quark states we also discuss the importance of various creation operators and give an estimate of the meson-meson and diquark-antidiquark percentages.
We report a new measurement of the production of electrons from open heavy-flavor hadron decays (HFEs) at mid-rapidity (|y| < 0.7) in Au+Au collisions at √sNN = 200 GeV. Invariant yields of HFEs are measured for the transverse momentum range of 3.5 < pT < 9 GeV/c in various configurations of the collision geometry. The HFE yields in head-on Au+Au collisions are suppressed by approximately a factor of 2 compared to that in p + p collisions scaled by the average number of binary collisions, indicating strong interactions between heavy quarks and the hot and dense medium created in heavy-ion collisions. Comparison of these results with models provides additional tests of theoretical calculations of heavy quark energy loss in the quark-gluon plasma.
We report a new measurement of the production of electrons from open heavy-flavor hadron decays (HFEs) at mid-rapidity (|y|< 0.7) in Au+Au collisions at sNN−−−√=200 GeV. Invariant yields of HFEs are measured for the transverse momentum range of 3.5<pT<9 GeV/c in various configurations of the collision geometry. The HFE yields in head-on Au+Au collisions are suppressed by approximately a factor of 2 compared to that in p+p collisions scaled by the average number of binary collisions, indicating strong interactions between heavy quarks and the hot and dense medium created in heavy-ion collisions. Comparison of these results with models provides additional tests of theoretical calculations of heavy quark energy loss in the quark-gluon plasma.
We report a new measurement of the production of electrons from open heavy-flavor hadron decays (HFEs) at mid-rapidity (|y|< 0.7) in Au+Au collisions at sNN−−−√=200 GeV. Invariant yields of HFEs are measured for the transverse momentum range of 3.5<pT<9 GeV/c in various configurations of the collision geometry. The HFE yields in head-on Au+Au collisions are suppressed by approximately a factor of 2 compared to that in p+p collisions scaled by the average number of binary collisions, indicating strong interactions between heavy quarks and the hot and dense medium created in heavy-ion collisions. Comparison of these results with models provides additional tests of theoretical calculations of heavy quark energy loss in the quark-gluon plasma.
Elliptic flow measurements from two-, four- and six-particle correlations are used to investigate flow fluctuations in collisions of U+U at sNN−−−√= 193 GeV, Cu+Au at sNN−−−√= 200 GeV and Au+Au spanning the range sNN−−−√= 11.5 - 200 GeV. The measurements show a strong dependence of the flow fluctuations on collision centrality, a modest dependence on system size, and very little if any, dependence on particle species and beam energy. The results, when compared to similar LHC measurements, viscous hydrodynamic calculations, and T$\mathrel{\protect\raisebox{-2.1pt}{R}}$ENTo model eccentricities, indicate that initial-state-driven fluctuations predominate the flow fluctuations generated in the collisions studied.
This thesis is concerned with the investigation of static and dynamic properties of quantum Heisenberg paramagnets in the absence of a magnetic field and therefore for vanishing magnetization. For this purpose a new formulation of the spin functional renormalization group (SFRG) is employed. The first manifestations of the SFRG were developed by Krieg and Kopietz, motivated by the FRG approach to ordinary field theories and the older works of Vaks, Larkin and Pikin on diagrammatic methods for spin operators.
The main idea is to study quantum spin systems by considering the evolution of correlation functions under a continuous deformation of the interaction between magnetic moments, starting from a solvable limit. This leads to nonperturbative results for quantities like the spin-spin correlation function. After a basic introduction to the phenomena and concomitant problems discussed in this thesis, a detailed description of the SFRG method in its initial formulation is given in the second chapter. We start with the generating functional of connected imaginary-time spin-correlation functions GΛ [h], for which an exact flow equation is derived. A particular issue, already pointed out by Krieg and Kopietz, arises here, namely the singular non-interacting limit of its subtracted Legendre transform ΓΛ [m]. As a consequence the initial condition of that functional does not have a proper series expansion in powers of m. This prevents us from working directly within a pure one-particle irreducible (1-PI) parametrization of the correlation functions, as is often done in the context of field theories. Thus motivated, we develop a workaround explicitly tailored to paramagnets, which provides us with a functional that has a well-behaved Legendre transform. The new approach is based on a different treatment of fluctuations at zero and finite frequencies, analogous to a previous hybrid formulation for the symmetry-broken phase. Certain properties, considered to be highly relevant for isotropic paramagnets, as well as previous observations, already made in the study of simpler spin systems like the Ising model, serve as additional justifications for choosing this construction.
In the third chapter our new method is assessed by calculating the dynamic susceptibility G(k, iω) and thus the dynamic structure factor S(k, ω) in the symmetric phase. For this purpose an approximate integral equation for the dynamic polarization function Π̃(k, iω) was derived. This equation results from a truncation of the hierarchy of flow equations and contains static quantities, that are assumed to be known from another source. Our first application is the high-temperature limit T → ∞ in d ≤ 3 dimensions. Salient features, believed to be part of the spin dynamics in isotropic Heisenberg magnets are also exhibited by our solution, like (anomalous) diffusion in a suitable hydrodynamic limit. Moreover we obtain the same order of magnitude for the diffusion coefficient D as in experiments and other theoretical calculations. Other aspects do not entirely agree with previous approaches.
Afterwards we continue by investigating systems close to the critical point Tc. Dynamic scaling forms for Π̃(k, iω) and S(k, ω), which, like spin diffusion, are postulated on the basis of quite general physical arguments, are reproduced. Agreement of the line-shapes 2with neutron scattering experiments at T = Tc is found to be satisfying, with deviations for ω → 0, that may be attributed to the simplicity of the approximation, like at infinite temperature.
Finally, we focus our attention on the thermodynamic properties of isotropic Heisenberg paramagnets by calculating the static susceptibility G(k). For this purpose we employ simple truncation schemes of the flow equations for the static self-energy ΣΛ (k) and four-spin vertex ΓΛ , together with a basic ansatz for the dynamic polarization Π̃(k, iω) in quantum systems. As a result we obtain transition temperatures Tc of three-dimensional nonfrustrated magnets within an accuracy of 5 percent compared to established benchmark values from Quantum Monte Carlo and high temperature expansion series. We conclude this chapter by giving an outlook on the application of our method to frustrated systems, which may require a combined non-trivial calculation of static and dynamic properties.
Elliptic flow measurements from two-, four- and six-particle correlations are used to investigate flow fluctuations in collisions of U+U at sNN−−−√ = 193 GeV, Cu+Au at sNN−−−√ = 200 GeV and Au+Au spanning the range sNN−−−√ = 11.5 - 200 GeV. The measurements show a strong dependence of the flow fluctuations on collision centrality, a modest dependence on system size, and very little if any, dependence on particle species and beam energy. The results, when compared to similar LHC measurements, viscous hydrodynamic calculations, and Glauber model eccentricities, indicate that initial-state-driven fluctuations predominate the flow fluctuations generated in the collisions studied.
This work aimed to investigate the regulation and activity of 5-lipoxygenase (5-LO), the central enzyme in leukotriene biosynthesis, in two colorectal cancer cell lines. The leukotriene pathway is positively correlated with the progression of several solid malignancies; however, factors regulating 5-LO expression and activity in tumors are poorly understood.
Cancer development, as well as cancer progression, are strongly dependent on the tumor microenvironment. In the conventional monolayer culture of cancer cell lines, cell-matrix and cell-cell interactions present in native tumors are absent. Furthermore, it is already known that various colon cancer cell lines dysregulate several important signaling pathways due to 3D growth. Therefore, the expression of the leukotriene cascade in HT-29 and HCT-116 colorectal cancer cells was investigated within a three-dimensional context using multicellular tumor spheroids to mimic a more physiological environment compared to conventional cell culture. Especially the expression of 5-LO, cPLA2α, and LTA4 hydrolase was altered due to threedimensional (3D) cell growth, which was investigated by qPCR and Western blot analysis. High cellular density in monolayer cultures led to similar results. The observed 5-LO upregulation was found inversely correlated with cell proliferation, determined by cell cycle analysis, and activation of PI3K/mTORC-2- and MEK-1/ERK-dependent pathways, determined using pharmacological pathway inhibition, stable shRNA knockdown cell lines, and analysis via qPCR and Western blot analysis. Following, the transcription factor E2F1 and its target gene MYBL2 were identified to play a role in the repression of 5-LO during cell proliferation. For this purpose, several stable MYBL2 over-expression and ALOX5 reporter cell lines were prepared and analyzed. Since 5-LO was already identified as a direct p53 target gene, the influence of p53, which is variably expressed in the cell lines (HT-29, p53 R273H mut; HCT-116 p53 wt; HCT-116 p53 KO), was investigated as well. Furthermore, HCT-116 cells carrying a p53 knockout were investigated. The PI3K/mTORC-2- and MEK-1/ERK-dependent suppression of 5-LO was also found in tumor cells from other origins (Capan-2, Caco-2, MCF-7), which was determined using pharmacological pathway inhibition and following analysis via qPCR. This suggests that the identified mechanism might apply to other tumor entities as well.
5-LO activity was previously described as attenuated in HT-29 and HCT-116 cells compared to polymorphonuclear leukocytes, which express a highly active 5-LO. However, the present study showed that the enzyme activity is indeed low but inducible in HT-29 and HCT-116 cells. Of note, the general lipid mediator profile and the mediator concentrations were comparable to those of M2 macrophages. Finally, the analysis of substrate availability in HT-29 and HCT-116 cells revealed a vast difference between formed metabolite concentrations and supplemented fatty acid concentrations, indicating that the substrates are either transformed into lipoxygenase-independent metabolites or are esterified into the cellular membrane.
In summary, the data presented in this work demonstrate that 5-LO expression and activity are tightly regulated in HT-29 and HCT-116 cells and fine-tuned due to environmental conditions. The cells suppress 5-LO during proliferation but upregulate the expression and activity of the enzyme under cellular stress-triggering conditions. This implies a possible role of 5-LO in manipulating the tumor stroma to support a tumor-promoting microenvironment.
Azimuthal anisotropy measurement of (multi-)strange hadrons in Au+Au collisions at √sNN = 54.4 GeV
(2022)
Azimuthal anisotropy of produced particles is one of the most important observables used to access the collective properties of the expanding medium created in relativistic heavy-ion collisions. In this paper, we present second (v2) and third (v3) order azimuthal anisotropies of K0S, ϕ, Λ, Ξ and Ω at mid-rapidity (|y|<1) in Au+Au collisions at sNN−−−√ = 54.4 GeV measured by the STAR detector. The v2 and v3 are measured as a function of transverse momentum and centrality. Their energy dependence is also studied. v3 is found to be more sensitive to the change in the center-of-mass energy than v2. Scaling by constituent quark number is found to hold for v2 within 10%. This observation could be evidence for the development of partonic collectivity in 54.4 GeV Au+Au collisions. Differences in v2 and v3 between baryons and anti-baryons are presented, and ratios of v3/v3/22 are studied and motivated by hydrodynamical calculations. The ratio of v2 of ϕ mesons to that of anti-protons (v2(ϕ)/v2(p¯)) shows centrality dependence at low transverse momentum, presumably resulting from the larger effects from hadronic interactions on anti-proton v2.
Azimuthal anisotropy measurement of (multi-)strange hadrons in Au+Au collisions at √sNN = 54.4 GeV
(2023)
Azimuthal anisotropy of produced particles is one of the most important observables used to access the collective properties of the expanding medium created in relativistic heavy-ion collisions. In this paper, we present second (v2) and third (v3) order azimuthal anisotropies of K0S, ϕ, Λ, Ξ and Ω at mid-rapidity (|y|<1) in Au+Au collisions at sNN−−−√ = 54.4 GeV measured by the STAR detector. The v2 and v3 are measured as a function of transverse momentum and centrality. Their energy dependence is also studied. v3 is found to be more sensitive to the change in the center-of-mass energy than v2. Scaling by constituent quark number is found to hold for v2 within 10%. This observation could be evidence for the development of partonic collectivity in 54.4 GeV Au+Au collisions. Differences in v2 and v3 between baryons and anti-baryons are presented, and ratios of v3/v3/22 are studied and motivated by hydrodynamical calculations. The ratio of v2 of ϕ mesons to that of anti-protons (v2(ϕ)/v2(p¯)) shows centrality dependence at low transverse momentum, presumably resulting from the larger effects from hadronic interactions on anti-proton v2.
The elliptic (v2) and triangular (v3) azimuthal anisotropy coefficients in central 3He+Au, d+Au, and p+Au collisions at sNN−−−√ = 200 GeV are measured as a function of transverse momentum (pT) at mid-rapidity (|η|<0.9), via the azimuthal angular correlation between two particles both at |η|<0.9. While the v2(pT) values depend on the colliding systems, the v3(pT) values are system-independent within the uncertainties, suggesting an influence on eccentricity from sub-nucleonic fluctuations in these small-sized systems. These results also provide stringent constraints for the hydrodynamic modeling of these systems.
The elliptic (v2) and triangular (v3) azimuthal anisotropy coefficients in central 3He+Au, d+Au, and p+Au collisions at sNN−−−√ = 200 GeV are measured as a function of transverse momentum (pT) at mid-rapidity (|η|<0.9), via the azimuthal angular correlation between two particles both at |η|<0.9. While the v2(pT) values depend on the colliding systems, the v3(pT) values are system-independent within the uncertainties, suggesting an influence on eccentricity from sub-nucleonic fluctuations in these small-sized systems. These results also provide stringent constraints for the hydrodynamic modeling of these systems.
Weltweit gibt es laut WHO ca. 58 Millionen Menschen mit einer chronischen Hepatitis-C-Virus (HCV) Infektion und jährlich stecken sich ca. 1,5 Millionen Menschen neu mit diesem Virus an (Stand 2019). Da die Folge einer chronischen Hepatitis-C-Virus Infektion eine potenziell tödlich verlaufende Leberzirrhose oder die Entwicklung eines Hepatozellulären Karzinoms sein können, ist eine frühe Diagnose und eine adäquate Therapie eine wichtige Aufgabe in der Medizin.
Die bisherige Therapie erfolgte mittels pegyliertem Interferon und Ribavirin und seit einigen Jahren auch interferonfrei mittels Direkter Antiviraler Agenzien (DAA). Vor allem beim älteren Therapieregime konnten viele Nebenwirkungen und häufiger auch ein Therapieversagen auftreten, sodass ein leicht zu gewinnender Biomarker nützlich wäre, der die Patienten mit Therapieversagen frühzeitig und im besten Fall sogar vor Therapiebeginn detektieren kann.
In der vorliegenden Arbeit wurden die Spiegel von extrazellulär im Blut zirkulierender, leberspezifischer microRNA miR-122 auf Eigenschaften als solche potenzielle Biomarker untersucht. Dazu wurden die Patientenseren von insgesamt 60 Patienten mit chronischer Hepatitis-C-Virus Infektion analysiert, die mittels pegyliertem Interferon und Ribavirin behandelt wurden. Vor, während und nach der Therapie wurden verschiedene Laborparameter sowie die miR 122 in den Patientenseren bestimmt. 20 dieser Patienten zeigten ein dauerhaftes Ansprechen auf die Therapie (sustained virological response = SVR), 20 zeigten nach einem initialen Therapieansprechen ein Rückfall der Erkrankung (Relapse) und 20 Patienten sprachen gar nicht auf die Therapie an (Non-Responder = NR).
Zunächst wurden die sogenannten Baseline-Charakteristika der Patienten vor Therapiebeginn untersucht. Dabei konnten wir jedoch keinen Unterschied zwischen den Patientengruppen hinsichtlich der Alanin-Aminotransferase (ALT) und Aspartat-Aminotransferase (AST), zwei Laborparameter zur Bestimmung einer Leberschädigung, sowie der HCV-RNA, ein Parameter zur Bestimmung der Viruslast bei Patienten mit einer HCV-Infektion, feststellen.
Auch die miR-122-Spiegel zeigten vor Therapiebeginn keinen signifikanten Unterschied zwischen den drei Patientengruppen. Daraus wurde geschlossen, dass man die miR-122 vor Therapiebeginn nicht als prognostischen Marker für einen Therapieerfolg verwenden kann.
Beim Vergleich der miR-122-Spiegel mit den Laborparametern konnte eine signifikante Korrelation zwischen der miR-122 und der ALT, AST und der Gamma-Glutamyl-Transferase (GGT) festgestellt werden. Die miR-122 scheint somit ähnlich wie die anderen Laborparameter eine Leberzellschädigung widerzuspiegeln.
Nach dem Therapiebeginn konnte bereits ab Woche 4 ein signifikanter Unterschied zwischen den SVR und Non-Respondern sowie zwischen den Relapsepatienten und den Non-Respondern festgestellt werden. Jedoch war der Unterschied zwischen den SVR und den Relapse-Patienten nicht signifikant, sodass man weiterhin keine Unterscheidung dieser beiden Patientengruppen machen konnte.
Auch die ALT- und HCV-RNA-Spiegel zeigten einen ähnlichen Verlauf. In den Gruppen der SVR und Relapse-Patienten zeigte sich im Laufe der Therapie ein Rückgang der Parameter wohingegen die Gruppe der Non-Responder keine signifikante Dynamik aufwies.
Zum Schluss wurden die miR-122-Spiegel 12 bzw. 24 Wochen nach Therapieende bestimmt, dem sogenannten Zeitpunkt des Follow-Up bei dem der Therapieerfolg laut Leitlinie mit Hilfe der HCV-RNA-Messung bestimmt wird. Dabei konnte ein signifikanter Unterschied zwischen den miR-122-Spiegeln bei den SVR-Patienten und den anderen beiden Patientengruppen festgestellt werden.
In Zusammenschau dieser Ergebnisse kann man sagen, dass die miR-122 gut geeignet ist um ähnlich wie die HCV-RNA den Therapieverlauf widerzuspiegeln. Als prognostischer Parameter bzw. Biomarker für ein Therapieansprechen ist sie jedoch nicht geeignet, da keine Unterscheidung zwischen den einzelnen Patientengruppen vor Therapiebeginn möglich ist und während der Therapie lediglich die Non-Responder und nicht die Relapse-Patienten detektiert werden können.
Using limit linear series on chains of curves, we show that closures of certain Brill-Noether loci contain a product of pointed Brill-Noether loci of small codimension. As a result, we obtain new non-containments of Brill-Noether loci, in particular that dimensionally expected non-containments hold for expected maximal Brill-Noether loci. Using these degenerations, we also give a new proof that Brill-Noether loci with expected codimension −ρ≤⌈g/2⌉ have a component of the expected dimension. Additionally, we obtain new non-containments of Brill-Noether loci by considering the locus of the source curves of unramified double covers.
We prove that the projectivized strata of differentials are not contained in pointed Brill-Noether divisors, with only a few exceptions. For a generic element in a stratum of differentials, we show that many of the associated pointed Brill-Noether loci are of expected dimension. We use our results to study the Auel-Haburcak Conjecture: We obtain new non-containments between maximal Brill-Noether loci in Mg. Our results regarding quadratic differentials imply that the quadratic strata in genus 6 are uniruled.
Echolocating bats exhibit remarkable auditory behaviors, enabled by adaptations within and outside their auditory system. Yet, research in echolocating bats has focused mostly on brain areas that belong to the classic ascending auditory pathway. This study provides direct evidence linking the cerebellum, an evolutionarily ancient and non-classic auditory structure, to vocalization and hearing. We report that in the fruit-eating bat Carollia perspicillata, external sounds can evoke cerebellar responses with latencies below 20 ms. Such fast responses are indicative of early inputs to the bat cerebellum. In vocalizing bats, distinct spike train patterns allow the prediction with over 85% accuracy of the sound they are about to produce, or have just produced, i.e., communication calls or echolocation pulses. Taken together, our findings provide evidence of specializations for vocalization and hearing in the cerebellum of an auditory specialist.
On the potential for GWAS with phenotypic population means and allele-frequency data (popGWAS)
(2024)
This study explores the potential of a novel genome-wide association study (GWAS) approach for identifying loci underlying quantitative polygenic traits in natural populations. Extensive population genetic forward simulations demonstrate that the approach is generally effective for oligogenic and moderately polygenic traits and relatively insensitive to low heritability, but applicability is limited for highly polygenic architectures and pronounced population structure. The required sample size is moderate with very good results being obtained already for a few dozen populations scored. The method performs well in predicting population means even with a moderate false positive rate. When combined with machine learning for feature selection, this rate can be further reduced. The data efficiency of the method, particularly when using pooled sequencing, makes GWAS studies more accessible for research in biodiversity genomics. Overall, this study highlights the promise of this popGWAS approach for dissecting the genetic basis of complex traits in natural populations.
The elliptic (v2) and triangular (v3) azimuthal anisotropy coefficients in central 3He+Au, d+Au, and p+Au collisions at sNN−−−√ = 200 GeV are measured as a function of transverse momentum (pT) at mid-rapidity (|η|<0.9), via the azimuthal angular correlation between two particles both at |η|<0.9. While the v2(pT) values depend on the colliding systems, the v3(pT) values are system-independent within the uncertainties, suggesting an influence on eccentricity from sub-nucleonic fluctuations in these small-sized systems. These results also provide stringent constraints for the hydrodynamic modeling of these systems.
The elliptic (v2) and triangular (v3) azimuthal anisotropy coefficients in central 3He+Au, d+Au, and p+Au collisions at sNN−−−√ = 200 GeV are measured as a function of transverse momentum (pT) at mid-rapidity (|η|<0.9), via the azimuthal angular correlation between two particles both at |η|<0.9. While the v2(pT) values depend on the colliding systems, the v3(pT) values are system-independent within the uncertainties, suggesting an influence on eccentricity from sub-nucleonic fluctuations in these small-sized systems. These results also provide stringent constraints for the hydrodynamic modeling of these systems.
We present the first measurements of charge-dependent correlations on angular difference variables η1 − η2 (pseudorapidity) and φ1 − φ2 (azimuth) for primary charged hadrons with transverse momentum 0.15 <= pt <= 2 GeV/c and |η| <= 1.3 from Au–Au collisions at √sNN = 130 GeV. We observe correlation structures not predicted by theory but consistent with evolution of hadron emission geometry with increasing centrality from one-dimensional fragmentation of color strings along the beam direction to an at least two-dimensional hadronization geometry along the beam and azimuth directions of a hadron-opaque bulk medium.