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Using a sample of (10087±44)×106 J/ψ events, which is about fifty times larger than that was previously analyzed, a further investigation on the J/ψ→γ3(π+π−) decay is performed. A significant distortion at 1.84 GeV/c2 in the line-shape of the 3(π+π−) invariant mass spectrum is observed for the first time, which is analogous to the behavior of X(1835) and could be resolved by two overlapping resonant structures, X(1840) and X(1880). The new state X(1880) is observed with a statistical significance of 14.7σ. The mass and width of X(1880) are determined to be 1882.1±1.7±0.7 MeV/c2 and 30.7±5.5±2.4 MeV, respectively, which indicates the existence of a pp¯ bound state.
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.
Using a data sample corresponding to an integrated luminosity of 11.3 fb−1 collected at center-of-mass energies from 4.23 to 4.70 GeV with the BESIII detector, we observe the process e+e− → π0π0ψ2(3823) for the first time with a statistical significance of 6.0 standard deviations. The ratio of average cross sections for e+e− → π0π0ψ2(3823) and π+π−ψ2(3823) is determined to be R = σ[e+e− → π0π0ψ2(3823)] σ[e+e−→π+π−ψ2(3823)] = 0.57 ± 0.14 ± 0.05, which is consistent with expectations from isospin symmetry. Here and below, the first uncertainties are statistical and the second are systematic. The mass of the ψ2(3823) is measured to be M[ψ2(3823)] = 3824.5±2.4±1.0 MeV/c2. Due to the limited data sample, an upper limit of 18.8 MeV at 90% confidence level is set on the intrinsic width of ψ2(3823).
Using a data sample of (1.0087±0.0044)×1010 𝐽/𝜓 decay events collected with the BESIII detector at the center-of-mass energy of √𝑠=3.097 GeV, we present a search for the hyperon semileptonic decay Ξ0→Σ−𝑒+𝜈𝑒 which violates the Δ𝑆=Δ𝑄 rule. No significant signal is observed, and the upper limit on the branching fraction ℬ(Ξ0→Σ−𝑒+𝜈𝑒) is determined to be 1.6×10−4 at the 90% confidence level. This result improves the previous upper limit result by about one order of magnitude.
Insulin resistance and working memory exploring the role of blood glucose levels and lifestyle
(2023)
vIntroduction: Type 2 diabetes mellitus and dementia are among the leading causes for reduced quality of life and life expectancy worldwide and often occur comorbidly. Both diseases are linked by altered insulin signaling. Lifestyle factors and blood glucose monitoring play an essential role in the prevention and treatment of type 2 diabetes. So far, a relationship between blood glucose levels, lifestyle, and cognitive performance – a main symptom of dementia - has mainly been established in laboratory settings which reduces its ecological validity.
Objectives: This study uses ambulatory assessment and continuous glucose monitoring to explore the link between blood glucose levels, lifestyle and working memory in an ecological setting. We hypothesize that glycemic variations affect working memory performance in daily life. Second, we hypothesize that a high variance in blood glucose levels has a higher impact on working memory in insulin resistant participants. With this study, we aim to expand the knowledge on the relationship of insulin resistance and cognitive performance from the laboratory setting to everyday life.
Methods: This prospective, exploratory study will include 80 subjects with insulin resistance and 80 healthy controls. At baseline, blood indicators of insulin resistance will be measured to determine group assignment. Our ambulatory assessment includes smartphone-based sampling and sensor-based assessment. Therefore, cognitive performance will be recorded over three consecutive days using a smartphone. Four times a day, a numerical working memory task is prompted by signal-based alarms on the smartphone. Blood glucose levels are recorded in parallel by continuous glucose monitoring. In addition, lifestyle factors such as diet ad physical activity are examined. Diet is assessed by 24-h dietary protocols and movement acceleration by accelerometery.
Multilevel modelling will be used to map the relationship between blood glucose levels and working memory at the within- and between-person level. Diet and exercise are included in the analyses as additional predictors.
Results: Data collection started in March 2021 and is ongoing. Up to now, 40 insulin resistant participants and 36 healthy controls have been measured. Our preliminary results indicate a positive association between blood glucose levels and working memory performance at the within-person level (estimate = .48, 95% CI [.07, .89], p =0.022). At the between-person level the analysis revealed an inverse association between blood glucose levels and working memory performance (estimate = -.45, 95 % CI [-.86 - -.05], p = 0.029).
Conclusion: Our preliminary results are in line with studies showing that an acute rise in blood glucose levels leads to short-term improvements, while stable glucose profiles are beneficial in the long term. This might expand the understanding of the impact of insulin resistance on working memory and represent a target for early interventions. Our preliminary analysis needs to be repeated in our final dataset to confirm our results.
The amplification of magnetic fields plays an important role in explaining numerous astrophysical phenomena associated with binary neutron star mergers, such as mass ejection and the powering of short gamma-ray bursts. Magnetic fields in isolated neutron stars are often assumed to be confined to a small region near the stellar surface, while they are normally taken to fill the whole star in numerical modeling of mergers. By performing high-resolution, global, and high-order general-relativistic magnetohydrodynamic simulations, we investigate the impact of a purely crustal magnetic field and contrast it with the standard configuration consisting of a dipolar magnetic field with the same magnetic energy but filling the whole star. While the crust configurations are very effective in generating strong magnetic fields during the Kelvin–Helmholtz-instability stage, they fail to achieve the same level of magnetic-field amplification of the full-star configurations. This is due to the lack of magnetized material in the neutron-star interiors to be used for further turbulent amplification and to the surface losses of highly magnetized matter in the crust configurations. Hence, the final magnetic energies in the two configurations differ by more than 1 order of magnitude. We briefly discuss the impact of these results on astrophysical observables and how they can be employed to deduce the magnetic topology in merging binaries.
Post-merger gravitational-wave signal from neutron-star binaries: a new look at an old problem
(2023)
The spectral properties of the post-merger gravitational-wave signal from a binary of neutron stars encodes a variety of information about the features of the system and of the equation of state describing matter around and above nuclear saturation density. Characterizing the properties of such a signal is an “old” problem, which first emerged when a number of frequencies were shown to be related to the properties of the binary through “quasiuniversal” relations. Here we take a new look at this old problem by computing the properties of the signal in terms of the Weyl scalar ψ4. In this way, and using a database of more than 100 simulations, we provide the first evidence for a new instantaneous frequency, y f0 4, associated with the instant of quasi-time-symmetry in the dynamics, and which also follows a quasi-universal relation. We also derive a new quasi-universal relation for the merger frequency f h mer, which provides a description of the data that is 4 times more accurate than previous expressions while requiring fewer fitting coefficients. Finally, consistent with the findings of numerous studies before ours, and using an enlarged ensemble of binary systems, we point out that the ℓ = 2, m = 1 gravitational-wave mode could become comparable with the traditional ℓ = 2, m = 2 mode on sufficiently long timescales, with strain amplitudes in a ratio |h21|/|h22| ∼ 0.1–1 under generic orientations of the binary, which could be measured by present detectors for signals with a large signal-to-noise ratio or by third-generation detectors for generic signals should no collapse occur.
We search for the semi-leptonic decays Λ + c → Λπ+π−e+νe and Λ + c → pK0 Sπ−e+νe in a sample of 4.5 fb−1 of e+e− annihilation data collected in the center-of-mass energy region between 4.600 GeV and 4.699 GeV by the BESIII detector at the BEPCII. No significant signals are observed, and the upper limits on the decay branching fractions are set to be B(Λ+c → Λπ+π−e+νe ) < 3.9 × 10−4 and B(Λ + c → pK0Sπ−e+νe ) < 3.3 × 10−4 at the 90% confidence level, respectively.
Based on 4.5 fb−1 data taken at seven center-of-mass energies ranging from 4.600 to 4.699 GeV with the BESIII detector at the BEPCII collider, we measure the branching fractions of Λ + c → Σ + + hadrons relative to Λ + c → Σ +π +π −. Combining with the world average branching fraction of Λ + c → Σ +π +π −, their branching fractions are measured to be (0.377 ± 0.042 ± 0.020 ± 0.021)% for Λ + c → Σ +K+K−, (0.200 ± 0.023 ± 0.011 ± 0.011)% for Λ + c → Σ+K+π−, (0.414 ± 0.080 ± 0.030 ± 0.023)% for Λ + c → Σ +φ and (0.197 ± 0.036 ± 0.009 ± 0.011)% for Λ + c → Σ +K+K−(non-φ). In all the above results, the first uncertainties are statistical, the second are systematic and the third are from external input of the branching fraction of Λ + c → Σ +π +π −. Since no signal for Λ + c → Σ +K+π−π 0 is observed, the upper limit of its branching fraction is determined to be 0.13% at the 90% confidence level.
With data samples collected with the BESIII detector at seven energy points at √s = 3.68 − 3.71 GeV, corresponding to an integrated luminosity of 333 pb−1, we present a study of the Λ transverse polarization in the e+e− → ΛΛ¯ reaction. The signifcance of polarization by combining the seven energy points is found to be 2.6σ including the systematic uncertainty, which implies a non-zero phase between the transition amplitudes of the ΛΛ¯ helicity states. The modulus ratio and the relative phase of EM-psionic form factors combined with all energy points are measured to be RΨ = 0.71+0.10−0.10 ± 0.03 and ∆ΦΨ = 23+8.8−8.0 ± 1.6◦, where the frst uncertainties are statistical and the second systematic.
Bioactive small molecules are used in many research areas as important tools to uncover biological pathways, interpret phenotypic changes, deconvolute protein functions and explore new therapeutic strategies in disease relevant cellular model systems. To unlock the full potential of these small molecules and to ensure reliability of results obtained in cellular assays, it is crucial to understand the properties of these small molecules. These properties encompass their activity and potency on their designated target(s), their selectivity towards unintended off-targets and their phenotypic effects in a cellular system. Approved drugs often engage with multiple targets, which can be beneficial for some applications such as treatment of cancer where several pathways need to be inhibited for treatment efficacy. However, targeting multiple key proteins in diverse pathways also increases the possibility for unspecific or unwanted side effects. For many drugs the entire target space that they modulate is not known. This makes it difficult to use these drugs for target deconvolution or functional assays with the aim to understand the underlying biological processes. In contrast to drugs, for mechanistic studies, a good alternative are chemical tool compounds so called chemical probes that are usually exclusively selective as well as chemogenomic compounds, that inhibit several targets but have narrow selectivity profiles. Because they are mechanistic tools, chemical tool compounds must meet stringent quality criteria and they are therefore well characterized in terms of their potency, selectivity and cellular on-target activity. To ensure that an observed phenotypic effect caused by a compound can be attributed to the described target(s), it is essential to study also properties of chemical tools leading to unspecific cellular effects. There are a variety of unspecific effects that can be caused by physiochemical compound properties that can interfere with phenotypic assays as well as functional compound evaluations. One of these effects is low solubility causing toxicity or intrinsic fluorescence potentially interfering with assay readouts. But unanticipated cellular responses can also arise from unspecific binding, accumulation in cellular compartments or damage caused to organelles such as mitochondria or the cytoskeleton that can result in the induction of diverse forms of cell death.
In this study, we investigated the influence of a variety of small molecules on distinct cell states, by establishing and validating high-content imaging assays, which we called Multiplex assay. This assay portfolio enabled us to detect different cellular responses using diverse fluorescent reporters, such as the influence of a compound on cell viability, induction of cell death programs and modulation of the cell cycle. Additionally, general compound properties such as precipitation and intrinsic fluorescence were simultaneously detected. The assay is adaptable to assess other cellular properties of interest, such as mitochondrial health, changes in cytoskeletal morphology or phospholipidosis. A significant advantage of the assay is that we are using live cells, so we can capture dynamic cellular changes and fluctuations that can be crucial for the understanding of cellular responses.
In almost all parts of the world the industrialisation grows continuously and thus, the chemical pollution of natural waters has become a major public concern. A major consequence and one of the key environmental problems we are facing today is the increasing contamination of freshwater systems with chemicals. The chemicals are detected in wastewater, surface (river) water, ground water and drinking water ubiquitously in natural waters and not only in industrialised areas. The main point sources for water pollution and the release of these synthetic organic substances of human origin, so called micropollutants (MPs), are wastewater treatment plants (WWTPs). These MPs such as pharmaceuticals, personal care products, disinfectant chemicals, chemicals used in the industry and in households, contraceptives, hormones, food additives, artificial sweeteners, pesticides, biocides, and many emerging contaminants are only incompletely removed by the existing conventional wastewater treatment technologies. The MPs end up in the water cycle and have adverse effects on wildlife aquatic ecosystems and human health even at very low concentrations. Therefore, advanced wastewater treatment (AWWT) technologies, such as ozonation, treatment with activated carbon, biofiltration, membrane bioreactors (MBRs) or exposure to ultraviolet light are investigated as options to upgrade conventional WWTPs. However, several studies show that especially the ozonation of wastewater generates diverse transformation products (TPs) with unknown properties. These TPs could be more toxic than the mother compound. Thus, a post-treatment after the ozonation process is required.
The present thesis was part of the BMBF-funded TransRisk project dealing with “the characterisation, communication, and minimisation of risks of emerging pollutants and pathogens in the water cycle”. One main objective was the investigation of conventional treated wastewater after a full-scale ozonation with four post-treatments (each non-aerated and aerated granular activated carbon (GAC) filtration and biofiltration) in comparison to a MBR treatment of raw (untreated) wastewater separately and in combination with an additional ozonation on a pilot WWTP. For this purpose, the wastewater samples were characterised with a comprehensive battery of in vitro and in vivo bioassays. The in vitro bioassays were performed to detect endocrine activities (such as (anti)estrogenic and (anti)androgenic activities), genotoxicity, and mutagenicity. The results showed a decreased estrogenic activity due to the conventional wastewater treatment as well as the ozonation, but a distinct increase of the anti-estrogenic activity and the mutagenicity in the ozonated wastewater, possibly caused by new formed TPs, that were reduced after the post-treatments whereas the GAC filtration performed better than the biofiltration. The in vivo bioassays included for example the impact of the wastewater on mortality, reproduction, development, and energy reserves of the test organisms. The in vivo on-site tests with the mudsnail Potamopyrgus antipodarum and with the amphipod Gammarus fossarum indicated a major impact of conventional treated wastewater, ozonated wastewater, and MBR treated wastewater. The flow channel experiments in the laboratory with Gammarus pulex pointed to a serious impact of an estrogenic effluent on life-history traits of the amphipod. Finally, an ozonation of the wastewater with subsequent GAC filtration represented the most promising option. In addition, chemical analyses of 40 selected MPs, so called tracer substances, performed in parallel to the in vitro and in vivo bioassays underlined this assumption.
A second main objective was the optimisation of the preparation of water and wastewater samples for ecotoxicological in vitro bioassays because common sample preparation techniques are predominantly adapted for chemical analyses. Therefore, the impact of sample filtration, long-term acidification with following neutralisation as well as the enrichment with solid phase extraction (SPE) in combination with short-term acidification were investigated using amongst others raw (untreated) wastewater, hospital wastewater, conventional treated and ozonated wastewater, surface water, and ground water. Overall, eleven in vitro bioassays were performed for the detection of endocrine activities, genotoxicity, and mutagenicity. The results show that sample filtration and acidification/neutralisation significantly affected the outcome of the bioassays especially the anti-estrogenic activity and the mutagenicity whereas the sample filtration had a minor impact than the acidification. Thus, the testing of untreated (waste)water samples is advisable because the sample is minimally processed. Furthermore, the SPE extracts showed in parts high cytotoxic effects whereby no conclusions on the results of the bioassays were possible. However, the enrichment of endocrine activity and mutagenicity was predominantly effective but depended on the used SPE cartridge and the pH value of the (waste)water samples. Based on the results the use of a Telos C18/ENV cartridge and an acidified sample is recommendable. In the end, there is a need to optimise the sample preparation for in vitro bioassays to reach their maximum outcome for the best possible assessment of the water quality.
Die Arbeit behandelt die Messung von Photonen mit Teilchendetektoren, die auf digitalen Silizium-Pixelsensoren basieren. Diskutiert werden zwei wesentliche Schritte in den Upgrade-Programmen des ALICE-Experiments am CERN-LHC:
1. FOCAL-Detektor-Upgrade (2027): Untersuchung der Detektorantwort des elektromagnetischen Pixel-Kalorimeters EPICAL-2 und der Form elektromagnetischer Schauer durch Teststrahl-Messungen und Monte Carlo Simulationen.
2. ALICE 3-Upgrade (2035): Simulationsstudien zum Untergrund in der Messung von Photonen mit sehr kleinem Transversalimpuls.
Teil 1: Performance des elektromagnetischen Pixel-Kalorimeters EPICAL-2
Detektordesign und Testmessungen: EPICAL-2, ein SiW-Sandwich-Design-Kalorimeter mit ALPIDE Sensoren, besitzt eine Tiefe von ca. 20 Strahlungslängen und etwa 25 Millionen Pixel. Testmessungen wurden an der Universität Utrecht (kosmische Myonen) sowie am DESY und CERN-SPS (Elektronen) durchgeführt.
Simulation und Validierung: Das EPICAL-2 wird im Simulationspaket Allpix2 implementiert, um die Testmessungen zu validieren und das Detektorverhalten zu untersuchen. Systematische Variationen bestätigen die Stabilität und Reproduzierbarkeit der Simulation.
Datenaufbereitung und Schauerprofile: Im Rahmen der Datenanalyse werden fehlerhafte Pixel ausgeschlossen, Pixel-Treffer zu Clustern gruppiert, Chips kalibriert und der Strahlwinkel korrigiert. Das longitudinale Profil elektromagnetischer Schauer zeigt, dass das Schauermaximum in der Simulation etwas tiefer liegt als in den Testdaten, was auf zusätzliches Material oder eine unvollständige Beschreibung der Schauerentwicklung in der Simulation zurückzuführen sein könnte. Das laterale Profil zeigt, dass eine Schauertrennung im Millimeter-Bereich möglich ist.
Energieantwort und -auflösung: Die nicht-lineare Energieantwort wird sowohl in Testdaten als auch in Simulationen beobachtet. Die Energieauflösung des EPICAL-2 für Cluster ist besser als für Pixeltreffer und vergleichbar mit dem analogen CALICE-Prototypen. Simulationen ohne Strahlenergie-Fluktuationen zeigen eine bessere Energieauflösung als in den Testdaten.
Teil 2: Untergrund in der Messung von Photonen in ALICE 3
Simulationssetup: Die ALICE 3-Detektorgeometrie wird in GEANT4 implementiert, um den Untergrund in der Messung weicher Photonen zu untersuchen. Simulationen mit PYTHIA und GEANT4 zeigen, dass der Untergrund hauptsächlich aus Zerfallsphotonen und Photonen aus externer Bremsstrahlung besteht.
Ergebnisse der Untergrundstudien: Der Untergrund durch Photonen aus externer Bremsstrahlung dominiert und liegt im Akzeptanzbereich des FCT um einen Faktor von 5 bis 10 über dem theoretischen Signal weicher Photonen. In der Simulation wird das Material zu 8%—14% X0 in ALICE 3 bestimmt, wobei bereits bei 5% X0 der Untergrund genauso stark ist wie das erwartete Signal.
Möglichkeiten zur Untergrundreduzierung: Untersuchungen zeigen, dass ein Elektron-Veto das Signal-zu-Untergrund-Verhältnis um den Faktor 30 verbessern und eine Materialreduktion durch ein optimiertes Strahlrohr um den Faktor 7.
Die Ergebnisse des ersten Teils dieser Arbeit demonstrieren insgesamt die gute Performance des EPICAL-2 in Bezug auf die Energiemessung und die Bestimmung der Schauerform. Darüber hinaus unterstützen sie den Einsatz digitaler Kalorimeter im FOCAL-Upgrade des ALICE-Experiments und zeigen das Potenzial der digitalen Kalorimetertechnologie für zukünftige Hochenergiephysik-Experimente.
Die Ergebnisse des zweiten Teils dieser Arbeit liefern einen wesentliche Beitrag zum geplanten ALICE 3-Upgrade. Weiterhin veranschaulichen sie, wie ein Elektron-Veto und die Reduzierung des Materials zusammen eine vielversprechende Messstrategie bilden können.
Highlights
• The higher the extinction risk, the fewer exposure-effect data are available.
• Lack of studies in the Southern Hemisphere shows a spatial bias in the literature.
• Commonly studied pollutants are persistent organic pollutants, metals, pesticides.
• Pollution-effect studies focus on molecular and cellular levels.
• In silico and in vitro approaches aid in assessing in vivo effects.
Abstract
Marine mammals, due to their long life span, key position in the food web, and large lipid deposits, often face significant health risks from accumulating contaminants. This systematic review examines published literature on pollutant-induced adverse health effects in the International Union for Conservation of Nature (IUCN) red-listed marine mammal species. Thereby, identifying gaps in literature across different extinction risk categories, spatial distribution and climatic zones of studied habitats, commonly used methodologies, researched pollutants, and mechanisms from cellular to population levels. Our findings reveal a lower availability of exposure-effect data for higher extinction risk species (critically endangered 16%, endangered 15%, vulnerable 66%), highlighting the need for more research. For many threatened species in the Southern Hemisphere pollutant-effect relationships are not established. Non-destructively sampled tissues, like blood or skin, are commonly measured for exposure assessment. The most studied pollutants are POPs (31%), metals (30%), and pesticides (17%). Research on mixture toxicity is scarce while pollution-effect studies primarily focus on molecular and cellular levels. Bridging the gap between molecular data and higher-level effects is crucial, with computational approaches offering a high potential through in vitro to in vivo extrapolation using (toxico-)kinetic modelling. This could aid in population-level risk assessment for threatened marine mammals.
The STAR Collaboration presents measurements of the semi-inclusive distribution of charged-particle jets recoiling from energetic direct-photon γdir and neutral-pion (π0) triggers in p+p and central Au+Au collisions at √sNN=200 GeV over a broad kinematic range, for jet resolution parameters R=0.2 and 0.5. Medium-induced jet yield suppression is observed to be larger for R=0.2 than for 0.5, reflecting the angular range of jet energy redistribution due to quenching. The magnitude of suppression is similar for γdir- and π0-triggered data, which constrains the color-charge and path-length dependence of jet quenching. Theoretical model calculations incorporating jet quenching do not fully describe the measurements.
The longitudinal and transverse spin transfers to Λ (Λ¯¯¯¯) hyperons in polarized proton-proton collisions are expected to be sensitive to the helicity and transversity distributions, respectively, of (anti-)strange quarks in the proton, and to the corresponding polarized fragmentation functions. We report improved measurements of the longitudinal spin transfer coefficient, DLL, and the transverse spin transfer coefficient, DTT, to Λ and Λ¯¯¯¯ in polarized proton-proton collisions at √s = 200 GeV by the STAR experiment at RHIC. The data set includes longitudinally polarized proton-proton collisions with an integrated luminosity of 52 pb−1, and transversely polarized proton-proton collisions with a similar integrated luminosity. Both data sets have about twice the statistics of previous results and cover a kinematic range of |ηΛ(Λ¯¯¯¯)| < 1.2 and transverse momentum pT,Λ(Λ¯¯¯¯) up to 8 GeV/c. We also report the first measurements of the hyperon spin transfer coefficients DLL and DTT as a function of the fractional jet momentum z carried by the hyperon, which can provide more direct constraints on the polarized fragmentation functions.
The STAR Collaboration presents measurements of the semi-inclusive distribution of charged-particle jets recoiling from energetic direct-photon γdir and neutral-pion (π0) triggers in p+p and central Au+Au collisions at sNN−−−√=200 GeV over a broad kinematic range, for jet resolution parameters R=0.2 and 0.5. Medium-induced jet yield suppression is observed to be larger for R=0.2 than for 0.5, reflecting the angular range of jet energy redistribution due to quenching. The magnitude of suppression is similar for γdir- and π0-triggered data, which constrains the color-charge and path-length dependence of jet quenching. Theoretical model calculations incorporating jet quenching do not fully describe the measurements.
The longitudinal and transverse spin transfers to Λ (Λ¯¯¯¯) hyperons in polarized proton-proton collisions are expected to be sensitive to the helicity and transversity distributions, respectively, of (anti-)strange quarks in the proton, and to the corresponding polarized fragmentation functions. We report improved measurements of the longitudinal spin transfer coefficient, DLL, and the transverse spin transfer coefficient, DTT, to Λ and Λ¯¯¯¯ in polarized proton-proton collisions at s√ = 200 GeV by the STAR experiment at RHIC. The data set includes longitudinally polarized proton-proton collisions with an integrated luminosity of 52 pb−1, and transversely polarized proton-proton collisions with a similar integrated luminosity. Both data sets have about twice the statistics of previous results and cover a kinematic range of |ηΛ(Λ¯¯¯¯)| < 1.2 and transverse momentum pT,Λ(Λ¯¯¯¯) up to 8 GeV/c. We also report the first measurements of the hyperon spin transfer coefficients DLL and DTT as a function of the fractional jet momentum z carried by the hyperon, which can provide more direct constraints on the polarized fragmentation functions.
The longitudinal and transverse spin transfers to Λ (Λ¯¯¯¯) hyperons in polarized proton-proton collisions are expected to be sensitive to the helicity and transversity distributions, respectively, of (anti-)strange quarks in the proton, and to the corresponding polarized fragmentation functions. We report improved measurements of the longitudinal spin transfer coefficient, DLL, and the transverse spin transfer coefficient, DTT, to Λ and Λ¯¯¯¯ in polarized proton-proton collisions at s√ = 200 GeV by the STAR experiment at RHIC. The data set includes longitudinally polarized proton-proton collisions with an integrated luminosity of 52 pb−1, and transversely polarized proton-proton collisions with a similar integrated luminosity. Both data sets have about twice the statistics of previous results and cover a kinematic range of |ηΛ(Λ¯¯¯¯)| < 1.2 and transverse momentum pT,Λ(Λ¯¯¯¯) up to 8 GeV/c. We also report the first measurements of the hyperon spin transfer coefficients DLL and DTT as a function of the fractional jet momentum z carried by the hyperon, which can provide more direct constraints on the
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.
Havana's apartment-galleries have been vital venues for the city's art scene since the 1990s, hosting art exhibitions, workshops, and conferences. In the context of Cuba's limited art market and dearth of cultural institutions with international reach, these residential spaces have offered artists a unique opportunity to display their work and to connect with international art circuits. Focusing on the histories of three specific apartment-galleries - El Apartamento, Estudio Figueroa-Vives, and Avecez Art Space - this chapbook reflects on the complex interplay of the local and the global in the 'worlding' of cultural institutions.
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.
We analyze the experimental data on nuclei and hypernuclei yields recently obtained by the STAR collaboration. The hybrid dynamical and statistical approaches which have been developed previously are able to describe the experimental data reasonably. We discuss the intriguing difference between the yields of normal nuclei and hypernuclei which may be related to the properties of hypermatter at subnuclear densities. Most importantly new (hyper-)nuclei could be detected via particle correlations, and such measurements are relevant to pin down the production mechanism.
Gravitational waves from a core g-mode in supernovae as probes of the high-density equation of state
(2023)
Using relativistic supernova simulations of massive progenitor stars with a quark-hadron equation of state (EoS) and a purely hadronic EoS, we identify a distinctive feature in the gravitational-wave signal that originates from a buoyancy-driven mode (g-mode) below the proto-neutron star convection zone. The mode frequency lies in the range 200≲f≲800Hz and decreases with time. As the mode lives in the core of the proto-neutron star, its frequency and power are highly sensitive to the EoS, in particular the sound speed around twice saturation density.
Gravitational waves from a core g-mode in supernovae as probes of the high-density equation of state
(2023)
Using relativistic supernova simulations of massive progenitor stars with a quark-hadron equation of state (EoS) and a purely hadronic EoS, we identify a distinctive feature in the gravitational-wave signal that originates from a buoyancy-driven mode (g-mode) below the proto-neutron star convection zone. The mode frequency lies in the range 200≲f≲800Hz and decreases with time. As the mode lives in the core of the proto-neutron star, its frequency and power are highly sensitive to the EoS, in particular the sound speed around twice saturation density.
Highlights
• Stomach content analyses, parasitological and fecal examinations were performed on 73 raccoon dogs from Germany.
• 9 ecto- and 11 endoparasitic species could be identified of which 6 endoparasitic species have a human pathogenic potential.
• Stomach content was composed of one-third vegetable and two-thirds animal components.
• Invasive alien species can have negative impact on native animal species and can act as a carrier of various parasites.
Abstract
Originally from Asia, the raccoon dog Nyctereutes procyonoides is an invasive alien species in Europe, listed since 2019 on the List of invasive alien species of Union concern. The raccoon dog is considered to have negative impact on native biodiversity, as well as a crucial role in hosting and transmitting diverse parasites and pathogens of human and veterinary importance. In the present study, stomach content analyses and parasitological examinations were performed on 73 raccoon dogs from Germany. In addition, fecal samples were analyzed. The results of the study confirm the assumption that the examined raccoon dogs were infested with a various ecto- and endoparasite fauna. A total of 9 ecto- and 11 endoparasites were detected, with 6 of the endoparasites having human pathogenic potential. Trichodectes canis (P = 53.42%), Toxocara canis (P = 50.68%) and Uncinaria stenocephala (P = 68.49%) were the most abundant parasite species. The stomach contents consisted of approximately one-third vegetable and two-thirds animal components, composed of various species of amphibians, fish, insects, mammals and birds. Among them were specially protected or endangered species such as the grass frog Rana temporaria. The study shows that the raccoon dog exerts predation pressure on native species due to its omnivorous diet and, as a carrier of various parasites, poses a potential risk of infection to wild, domestic and farm animals and humans.
Highlights
• 234 raccoons were dissected, 23 parasite species could be detected.
• 14 new parasite species have been identified for raccoons in Europe.
• Compared to literature, a very high prevalence (95%) of B. procyonis was detected.
• The human pathogenic trematode P. muris was detected in raccoons for the first time.
Abstract
The invasive raccoon (Procyon lotor) is an abundant carnivore and considered as an important potential vector of infectious diseases and parasites in Europe. Raccoons show a broad, opportunistic, omnivorous food spectrum. Food supply and habitat quality in urban areas are very attractive for the generalist raccoon. This inevitably leads to increased interaction with humans, domestic animals and livestock, making the raccoon a potentially suitable zoonosis vector. In its autochthonous range, especially in the Eastern and Midwestern United States, the raccoon has been studied very intensively since the beginning of the 20th century. Whereas, basic field biology and parasitology studies in Germany and Europe are lacking and have only been conducted sporadically, regionally and on small sample sizes. In the presented study 234 raccoons from central Germany were comprehensively examined for their metazoan parasite fauna. The present study shows for the first time an extremely diverse parasite fauna in raccoons outside their native range and proves their essential role as intermediate hosts and hosts for ecto- and endoparasites. A total of 23 different parasite species were identified, five of which are human pathogens, 14 of which are new for the parasite fauna of raccoons in Europe. The human pathogenic raccoon roundworm Baylisascaris procyonis is the most common parasite species in this study, with a prevalence of up to 95%. The digenetic trematode Plagiorchis muris, another human pathogenic parasite species, was detected for the first time in raccoons. The ongoing spread of invasive carnivores and the associated spread and transmission of their parasites and other pathogens increases the potential health risk of wild and farmed animals as well as humans. An increase in parasitic diseases in humans (e.g. raccoon roundworm) is to be expected, especially in urban areas, where raccoons are becoming more and more abundant.
Highlights
• We propose a framework to address landscape effects on ecosystem services.
• We expect ecosystem service flows to be modulated by the amount and configuration of supply and demand areas.
• We stress the role of neutral areas in facilitating or hindering ecosystem service flows.
• Supply/demand ratios, spatial overlap, and ES characteristics need to be accounted for when assessing flows.
• We propose a research agenda with challenges to couple the effects of landscape configuration on ES flow.
Abstract
Despite advances in understanding the effects of landscape structure on ecosystem services (ES), many challenges related to these complex spatial interactions remain. In particular, the integration of landscape effects on different components of the service provision chain (supply, demand, and flow) remains poorly understood and conceptualized. Here we propose a theoretical framework to further explore how the spatial flow of ES can vary according to landscape structure (i.e. composition and configuration) emphasizing the role played by the configuration of supply, demand, and neutral areas, as well as individual characteristics of ES (e.g., service rivalry). For this, we expand the discussion on how landscape changes can affect ES flows and propose a theoretical representation of ES flows variation led by different supply-demand ratios. Additionally, we expand this discussion by integrating the potential effects of neutral areas in the landscape as well as of supply/demand spatial overlap. This novel approach links the spatial arrangement (e.g. fragmentation, network complexity, matrix resistance) usually captured by landscape metrics, and ratios of ES supply and demand areas to potential effects on spatial flows of ES. We discuss the application of this model using widely studied ES, such as pollination, pest control by natural enemies, and microclimate regulation. Finally, we propose a research agenda to connect the presented ideas with other prominent research topics that must be further developed to support landscape management targeting ES provision. The prominence of ES science calls for contributions such as this to give the scientific community the opportunity to reflect on the underlying mechanisms of ES and avoid oversimplified spatial assessments.
This bachelor thesis developed a pipeline for automatic processing of scanned hospital letters: HospLetExtractor. Hospital letters can contain valuable information about potential adverse drug reactions and useful case information relevant to pharmacovigilance. To make this data accessible, this thesis presents a pipeline consisting of image pre-processing, optical character recognition and post-processing. Pre-processing deskews the images, removes
lines and rectangles, reduces noise and applies super-resolution. For the post-processing a spell checking system was set up including a newly built word frequency dictionary for german medical terms based on a created corpus of german medical texts. Furthermore, classical and deep learning models for the classification of hospital letters were compared, in which the transformer-based models performed best. In order to train and test the models, a new
gold standard was created. By making these medical documents accessible for automatic analysis, hopefully a contribution can be made to expand the scope of pharmacovigilance.
The multistep PROTAC (PROteolysis TArgeting Chimeras) degradation process poses challenges for their rational development, as rate limiting steps determining PROTAC efficiency remain largely unknown. Moreover, the slow throughput of currently used endpoint assays does not allow the comprehensive analysis of larger series of PROTACs. Here we developed cell-based assays using NanoLuciferase and HaloTags, that allow measuring PROTAC induced degradation and ternary complex formation kinetics and stability in cells. Using PROTACs developed for degradation of WDR5, the characterization of the mode of action of these PROTACs in the early degradation cascade revealed a key role of ternary complex formation and stability. Comparing a series of ternary complex crystal structures highlighted the importance of an efficient E3-target interface for ternary complex stability. The developed assays outline a strategy for the rational optimization of PROTACs using a series of live cell assays monitoring key steps of the early PROTAC induced degradation pathway.
Significance The multistep PROTAC induced degradation process of a POI poses a significant challenge for the rational design of these bifunctional small molecules as critical steps that limit PROTAC efficacy cannot be easily assayed at required throughput. In addition, the cellular location of the POI may pose additional challenges as some cellular compartments, such as the nucleus, may not be easily reached by PROTAC molecules and the targeted E3 ligases may not be present in this cellular compartment. We propose therefore a comprehensive assay panel for PROTACs evaluation in cellular environments using a sensor system that allows continuous monitoring of the protein levels of the endogenous POI. We developed a cell line expressing WDR5 from its endogenous locus in fusion with a small sequence tag (HiBIT) that can be reconstituted to functional NanoLuciferase (NLuc). This system allowed continuous monitoring of endogenous WDR5 levels in cells and together with HaloTag system also the continuous monitoring of ternary complex (E3, WDR5 and PROTAC) formation. As this assay can be run at high throughput, we used this versatile system monitoring three diverse chemical series of WDR5 PROTACs that markedly differ in their degradation properties. Monitoring cell penetration, binary complex formation (PROTAC-WDR5 and PROTAC-VHL) as well as ternary complex formation we found that PROTAC efficiency highly correlated with synergy of ternary complex formation in cells. This study represents a first data set on diverse PROTACs studying this property in cellulo and it outlines a strategy for the rational optimization of PROTACs. It also provided kinetic data on ternary complex assembly and dissociation that may serve as a benchmark for future studies utilizing also kinetic properties for PROTAC development. Comparative structural studies revealed larger PROTAC mediated interaction surfaces for PROTACs that efficiently formed ternary complexes highlighting the utility of structure based optimization of PROTAC induced ternary complexes in the development process.
First study of reaction Ξ⁰n → Ξ⁻ p using Ξ⁰-nucleus scattering at an electron-positron collider
(2023)
Using ð1.0087 0.0044Þ × 1010 J=ψ events collected with the BESIII detector at the BEPCII storage ring, the process Ξ0n → Ξ−p is studied, where the Ξ0 baryon is produced in the process J=ψ → Ξ0Ξ¯ 0 and the neutron is a component of the 9 Be, 12C, and 197Au nuclei in the beam pipe. A clear signal is observed with a statistical significance of 7.1σ. The cross section of the reaction Ξ0 þ 9 Be → Ξ− þ p þ 8 Be is determined to be σðΞ0 þ 9 Be → Ξ− þ p þ 8 BeÞ¼ð22.1 5.3stat 4.5sysÞ mb at the Ξ0 momentum of 0.818 GeV=c, where the first uncertainty is statistical and the second is systematic. No significant H-dibaryon signal is observed in the Ξ−p final state. This is the first study of hyperon-nucleon interactions in electron-positron collisions and opens up a new direction for such research.
The Cabbibo-favored decay Λ+c→Ξ0K+π0 is studied for the first time using 6.1 fb−1 of e+e− collision data at center-of-mass energies between 4.600 and 4.840 GeV, collected with the BESIII detector at the BEPCII collider. With a double-tag method, the branching fraction of the three-body decay Λ+c→Ξ0K+π0 is measured to be (7.79±1.46±0.71)×10−3, where the first and second uncertainties are statistical and systematic, respectively. The branching fraction of the two-body decay Λ+c→Ξ(1530)0K+ is (5.99±1.04±0.29)×10−3, which is consistent with the previous result of (5.02±0.99±0.31)×10−3. In addition, the upper limit on the branching fraction of the doubly Cabbibo-suppressed decay Λ+c→nK+π0 is 7.1×10−4 at the 90% confidence level. The upper limits on the branching fractions of Λ+c→Σ0K+π0 and ΛK+π0 are also determined to be 1.8×10−3 and 2.0×10−3, respectively.
Using data samples with an integrated luminosity of 22.42 fb−1 collected by the BESIII detector operating at the BEPCII storage ring, we measure the cross sections of the $e^{+}e^{-}\rightarrow\etaJ/\psi$ process at center-of-mass energies from 3.808 to 4.951 GeV. Three structures are observed in the line shape of the measured cross sections. A maximum-likelihood fit with ψ(4040), two additional resonances, and a non-resonant component is performed. The mass and width of the first additional state are (4219.7±2.5±4.5)MeV/c2 and (80.7±4.4±1.4)MeV, respectively, consistent with the ψ(4230). For the second state, the mass and width are (4386±13±17)MeV/c2 and (177±32±13)MeV, respectively, consistent with the ψ(4360). The first uncertainties are statistical and the second ones are systematic. The statistical significance of ψ(4040) is 8.0σ and those for ψ(4230) and ψ(4360) are more than 10.0σ.
The simultaneous inhibition of HDACs and BET proteins has shown promising anti-proliferative effects against different cancer types, including the difficult to treat pancreatic cancer. In this work, the strategy of concurrently targeting HDACs and BET proteins was pursued by developing different types of dual inhibitors.
By developing a novel scaffold that selectively inhibits HDAC1/2 together with BET proteins in cells, an effective tool for the investigation of pancreatic cancer, and other diseases which are sensitive to epigenetic processes, was created. The compound’s small size further gives the opportunity to further develop the inhibitor towards optimized pharmacokinetic properties, potentially resulting in a drug for cancer treatment.
A second novel approach that was pursued, was the development of a small-molecule degrader, targeting HDACs and BET proteins. Through synthesizing a variety of different molecules, a compound that was capable of lowering BRD4 levels and, at the same time, increasing histone acetylation was developed. While additional mechanistic investigations are needed to verify the degradation, the potent antiproliferative effects in pancreatic cancer cells encourage further studies following this alternative new strategy.
This thesis comprises the usage of two commonly known hinge-binding moieties in drug discovery. First, the quinazoline scaffold of gefitinib (5) was utilized in a macrocyclization strategy to introduce selectivity. In general, the quinazoline hinge-binding moiety is a commonly used scaffold which can be found in 14% of approved kinase inhibitors. The most familiar applications are EGFR inhibitors such as gefitinib (5), erlotinib (6), afatinib, or dacomitinib for the treatment of NSCLC. But other kinases like CDK2, CDK4, or p38 are reported targets as well.
The N-phenylquinazolin-4-amine moiety of gefitinib (5) was conserved however, the residues at the aromatic ring in the linker were modified, the residue targeting the solvent-exposed region was varied, and the linker at the C6 position of the quinazoline was adjusted to enable the macrocyclization. An overview of the structural modifications is shown in Figure 35A.
Kinome-wide screening of gefitinib (5) revealed several off-targets besides EGFR (Figure 35B), making it an excellent starting point for a macrocyclization strategy. Introducing a linker to the N phenylquinazoline-4-amine scaffold and retaining the residues on the aromatic ring as well as the methoxy group targeting the solvent-exposed region improved the selectivity profile and the efficacy towards EGFR WT and its mutants. Truncation of the linker moiety led to the mutant selective macrocycle 26f with an excellent kinome-wide selectivity profile (Figure 35B). An inhibitor that is effective on EGFR mutations while ineffective on the EGFR WT could represent an enhancement of patient treatment, as it potentially causes less side effects. Further studies could determine the effect of the most promising macrocycles in lung cancer cell lines. Additionally, the pharmacokinetic properties could be optimized, e.g. by introducing solubilizing groups, targeting the solvent-exposed region.
The second scaffold comprises the 3-aminopyrazole-based hinge-binding moiety. It is a privileged scaffold in medicinal chemistry for the development of kinase inhibitors. Previous publications report the anti-proliferative and anti-cancer potential of pyrazole-based molecules. They play a crucial role in the treatment of various diseases and cancer types like inflammation disorders, lymphoma, or breast cancer. This scaffold can be found e.g. in the aurora kinase inhibitor tozasertib or in the promiscuous kinase inhibitor 23, published by Statsuk et. al. Rescreening compound 23 in a comprehensive kinase panel against 468 human protein kinases confirmed the unselective behavior with a selectivity score of S35 = 0.56 (Figure 36B), making it a great starting point for further optimizations. The N-(1H-pyrazol-3-yl)pyrimidin-4-amine scaffold was conserved however, the residues targeting the solvent-exposed region were varied and different linkers were attached.
The introduction of different residues at the pyrazole dramatically influenced the selectivity profile of the desired kinases. Ester moieties caused to a favorable combination of selectivity and potency towards the kinase of interest CDK16. The removal of additional residues at the pyrimidine, targeting the solvent-exposed region, increased the efficiency towards CDK16. Further optimization led to the highly potent and selective CDK16 inhibitor 98d (IC50 = 33 nM). NanoBRETTM screening against the complete CDK family revealed a preferred inhibition of the PCTAIRE and PFTAIRE subfamily with cellular IC50 values of 20 nM – 120 nM and 50 nM – 180 nM, respectively. A FUCCI cell cycle assay and viability assessment of 98d confirmed previously published results, reporting a G2/M cell cycle arrest followed by apoptosis and accumulation of p27 through knockout of CDK16 in SCC cells. Consequently, further studies could evaluate the anti-tumor activity of 98d in SCC and NSCLC or elucidate the effect of 98d in AMPK-related macroautophagy. 98d represents a novel tool compound to investigate the understudied kinases of the PCTAIRE family and enable to enlighten the biological role of those kinases.
Macrocyclization of the N-(1H-pyrazol-3-yl)pyrimidin-4-amine core resulted in the selective BMPR2 inhibitor 110a. It showed a good binding affinity towards BMPR2 with a KD value of 205 nM as well as a good potency with an IC50 value of 506 nM. A comprehensive selectivity screen against 468 kinases revealed an excellent selectivity profile with S35 = 0.01. As no BMPR2 inhibitors have been published so far, 110a represents a novel compound that may provide further insights into the canonical BMP pathway, noncanonical signaling, or its impact on BMPR2-associated diseases like PAH.
The introduction of additional residues targeting the solvent-exposed region shifted the selectivity towards the MST kinases. The exchange from the pyrimidine to a quinazoline moiety resulted in the highly potent and selective macrocyclic MST3 inhibitor 113c. NanoBRETTM measurements demonstrated the preferred inhibition of MST3 with IC50 values of 210 nM and 30 nM for intact and lysed cells, respectively. A weaker activity could be seen for MST4 with 1.8 µM and 510 nM, while MST1 and MST2 were not affected. To date, no selective MST3 inhibitors have been published, making 113c a valuable tool compound for further functional studies. As MST3 is influencing the cell cycle progression, 113c could be tested in a further cell cycle assay to elucidate the inhibitory effect of 113c on MST3 and consequently on the cell cycle. Furthermore, the anti-tumor activity of 113c in breast cancer could be determined, as Madsen et. al. reported a high MST3 and MST4 activity triggered by FAM40B mutations.
Lipid acquisition and transport are fundamental processes in all organisms, but many of the key players remain unidentified. Here, we elucidate the lipid-cycling mechanism of the Mycoplasma pneumoniae membrane protein P116. We show that P116 not only extracts lipids from its environment but also self-sufficiently deposits them into both bacterial and eukaryotic cell membranes as well as liposomes. Our structures and molecular dynamics simulation show that the N-terminal region of P116, which resembles an SMP domain, is responsible for perturbing the membrane, while a hydrophobic pocket exploits the chemical gradient to collect the lipids and the protein’s dorsal side acts as a mediator of membrane directionality. Furthermore, ligand binding and growth curve assays suggest the potential for designing small molecule inhibitors targeting this essential and immunodominant protein. We show that P116 is a versatile lipid acquisition and delivery machinery that shortcuts the multi-protein pathways used by more complex organisms. Thus, our work advances the understanding of common lipid transport strategies, which may aid research into the mechanisms of more complex lipid-handling machineries.
Protein kinases are key signalling molecules and transduce intracellular signals via the post-translational phosphorylation of substrate proteins, often other protein kinases. Dysregulation of this protein family has been linked to many diseases including neurodegenerative diseases, inflammation and cancer and amplifications of kinases play important roles as diagnostic biomarkers in a variety of cancers. Various strategies have been developed to treat dysregulated protein kinases. Most commonly, chemical small molecule inhibitors are used to modulate protein kinase activity in cancer cells. Many inhibitor and general research efforts have focused only on a small subset of protein kinases, resulting in a large portion of the kinome, the so-called “dark” kinome, remaining largely unexplored. As part of the strategy to develop inhibitors, it is crucial to understand the structure-activity-relationships (SAR) of small molecules to the activity towards the targets based on understanding small molecule-target affinities as determined by biophysical, biochemical, and cellular methods. However, not always do in vitro determined affinities, which are frequently used as basis for SAR considerations, correlate with the cellular affinity. For protein kinases in particular, it has been shown that the cellular concentration of the natural substrate adenosine-triphosphate (ATP) plays a critical role for the resulting small molecule affinity, as substrate and inhibitor frequently compete for the same binding site of the protein kinase. The cellular target engagement assay NanoBRET is a versatile assay that overcomes this problem and can be used to assess binding of a compound to the full-length protein kinase, in the presence of natural binding partners. Another important factor in inhibitor optimization is the selectivity of the molecule within the family of protein kinases. When comparing the selectivity profiles of small molecule kinase inhibitors in vitro and in cells, different profiles can be observed. Frequently, a compound, binds fewer protein kinases with high affinity in cells, indicating that cellular profiling of protein kinase inhibitors is necessary to understand the selectivity profile of an inhibitor.
The goal of this work was to understand cellular SARs of inhibitors for kinases and dark kinases in medicinal chemistry projects, and to understand the selectivity profiles of existing small molecules in cells, including already approved drugs and clinically used kinases inhibitors. The cellular potency and selectivity aspects guided optimization of the inhibitors towards selective small molecules ‘chemical probes’ or highly validated inhibitors with a narrow selectivity profile as part of ‘chemogenomic libraries’. One strategy to improve selectivity has been to use sterically restricted cyclic small molecules, called macrocycles, that allow fewer conformations of the molecule than their non-cyclic parent compound. In this thesis the dark kinase STK17A was investigated. Macrocyclization was used to develop a selective chemical probe molecule that is also selective in the cellular context. For another kinase, SIK2, a rational design approach was used to exclude off-targets bound by the lead structure, resulting in a chemical probe that selectively targets the SIK1/2/3 proteins. Assessing cellular potency of another series of inhibitors, a probe was developed for the PCTAIRE subfamily of the CDK kinases. This required co-expression of the binding partners of CDKs, the cyclins, in cells to obtain a functional assay. To identify new candidates for the neglected family of splicing kinases comprising the CLK, SRPK, DYRK and HIPK protein kinase subfamilies, a literature review was conducted, and the best small molecule candidates were compared for their target engagement in cells. This led to a series of small molecule inhibitors that may be used as a set or single agents to target the CLK proteins and SRPK proteins or in combination to target the remaining proteins. In search of new starting points for this subfamily of kinases, an initial screen with NanoBRET technology was performed using a library of over 2000 inhibitors, and new starting points were identified. Additionally, a set of clinical and approved small molecule kinase inhibitors was assessed for their selectivity in cells. Several highly selective molecules were identified that were much less selective in in vitro approaches. The set of data allowed for a comprehensive comparison of cellular potencies with published data using in vitro binding, in vitro activity and data obtained from cell lysates and identified several protein kinases that would need to be investigated in cells...
5-iodotubercidin sensitizes cells to RIPK1-dependent necroptosis by interfering with NFκB signaling
(2023)
Receptor-interacting protein kinases (RIPK) −1 and −3 are master regulators of cell fate decisions in response to diverse stimuli and are subjected to multiple checkpoint controls. Earlier studies have established the presence of distinct IKK1/2 and p38/MK2-dependent checkpoints which suppress RIPK1 activation by directly phosphorylating it at different residues. In the present study, we investigated TNF-induced death in MAPK-activated protein kinase 2 (MK2)-deficient cells and show that MK2-deficiency or inactivation predominantly results in necroptotic cell death, even in the absence of caspase inhibition. While MK2-deficient cells can be rescued from necroptosis by RIPK1 inhibitors, RIPK3 inhibition seems to revert the process triggering apoptosis. To understand the mechanism of this necroptosis switch, we screened a 149-compound kinase inhibitor library for compounds which preferentially sensitize MK2-deficient MEFs to TNF-induced cell death. The most potent inhibitor identified was 5-Iodotubericidin, an adenosine analogue acting as adenosine kinase and protein kinase inhibitor. 5-ITu also potentiated LPS-induced necroptosis when combined with MK2 inhibition in RAW264.7 macrophages. Further mechanistic studies revealed that 5-Iodotubericidin induces RIPK1-dependent necroptosis in the absence of MK2 activity by suppressing IKK signaling. The identification of this role for the multitarget kinase inhibitor 5-ITu in TNF-, LPS- and chemotherapeutics-induced necroptosis will have potential implications in RIPK1-targeted therapies.
Autism Spectrum Disorder (ASD) is a neurodevelopmental condition with an onset in early development. ASD has varying degrees of severity and thus affects people differently throughout their lives. Early diagnosis of ASD is essential to provide children with individually-tailored support.8 Eye-tracking may contribute to an earlier diagnosis: Several studies showed differences in eye movements between people with autism spectrum disorder (ASD) and typically developing controls (TD). Different eye movements may contribute to different visual perception that perpetuates to problems in attention, communication and social interaction.
Eye movements are divided into: (1) Fixations (2) Saccades (fast and short eye movements) and (3) Smooth Pursuit Eye Movements (SPEM). SPEM follow the target in a continuous manner. The latter are the subject of the present thesis. SPEM consist of two phases: the open loop phase (= phase of initiation, first 50- 100ms) and the closed loop phase (= phase of maintenance, after about 100ms). SPEM are usually measured by a gain index. It is defined as the ratio of smooth pursuit velocity and visual target velocity and ideally equals to 1.2
In young children, corneal-reflection (CR) eye-tracking is usually applied to quantify eye movement. It allows precise measurements without the use of potentially intrusive devices.
Studies in ASD reported deficits in open loop and closed loop pursuit in children and adults with a mean age of 19.32 (TD) and 20.04 (ASD) years. However, SPEM in preschoolers with ASD remain understudied, although this developmental phase is crucial to the development of non-social and social attentional abilities.
In the present study 66 toddlers and preschoolers (18 to 72 months; ASD: n = 33, TD: n = 33) with matched cognitive abilities and sex were assessed. The main objective was to compare the gain index (Smooth Pursuit Gain = SPG). SPEM were compared between groups with gain index as a dependent measure. We hypothesized that participants with ASD show lower average gain compared to the control group.
We could show a significant group influence on the gain when considering interactions between target velocity and group (p = 0.041). The TD group showed a greater dependence on the increasing object speed than the ASD group with a trend of -0.30 ± 0.11 in the TD group and a trend of -0.13 ± 0.12 in the ASD group. Across groups, the gain decreased with increasing target velocity and dropped faster in vertical than in horizontal trials. Additionally, participants showed a lower SPG in vertical sequences than in horizontal sequences. This supports the general validity of the measure.
Toddlers and preschoolers represent a group that has been subject of little research to date. In addition, there has been only a limited number of studies analyzing SPEM in ASD. To check for a possible group difference without interactions a study with a larger sample size at fixed target velocity and target direction should follow.
We analyze the experimental data on nuclei and hypernuclei yields recently obtained by the STAR collaboration. The hybrid dynamical and statistical approaches which have been developed previously are able to describe the experimental data reasonably. We discuss the intriguing difference between the yields of normal nuclei and hypernuclei which may be related to the properties of hypermatter at subnuclear densities. New (hyper)nuclei could be detected via particle correlations. Such measurements are important to pin down the production mechanism.
The family of cubic noncentrosymmetric 3-4-3 compounds has become a fertile ground for the discovery of novel correlated metallic and insulating phases. Here, we report the synthesis of a new heavy fermion compound, Ce3Bi4Ni3. It is an isoelectronic analog of the prototypical Kondo insulator Ce3Bi4Pt3 and of the recently discovered Weyl-Kondo semimetal Ce3Bi4Pd3. In contrast to the volume-preserving Pt-Pd substitution, structural and chemical analyses reveal a positive chemical pressure effect in Ce3Bi4Ni3 relative to its heavier counterparts. Based on the results of electrical resistivity, Hall effect, magnetic susceptibility, and specific heat measurements, we identify an energy gap of 65-70 meV, about 8 times larger than that in Ce3Bi4Pt3 and about 45 times larger than that of the Kondo-insulating background hosting the Weyl nodes in Ce3Bi4Pd3. We show that this gap as well as other physical properties do not evolve monotonically with increasing atomic number, i.e., in the sequence Ce3Bi4Ni3-Ce3Bi4Pd3-Ce3Bi4Pt3, but instead with increasing partial electronic density of states of the d orbitals at the Fermi energy. To understand under which condition topological states form in these materials is a topic for future studies.
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.
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 results on an elastic cross section measurement in proton-proton collisions at a center-of-mass energy s√=510 GeV, obtained with the Roman Pot setup of the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The elastic differential cross section is measured in the four-momentum transfer squared range 0.23≤−t≤0.67 GeV2. We find that a constant slope B does not fit the data in the aforementioned t range, and we obtain a much better fit using a second-order polynomial for B(t). The t dependence of B is determined using six subintervals of t in the STAR measured t range, and is in good agreement with the phenomenological models. The measured elastic differential cross section dσ/dt agrees well with the results obtained at s√=546 GeV for proton--antiproton collisions by the UA4 experiment. We also determine that the integrated elastic cross section within the STAR t-range is σfidel=462.1±0.9(stat.)±1.1(syst.)±11.6(scale) μb.
We measure triangular flow relative to the reaction plane at 3 GeV center-of-mass energy in Au+Au collisions at RHIC. A significant v3 signal is observed for protons, whose magnitude increases for higher rapidity, higher transverse momentum, and more peripheral collisions. The triangular flow is essentially rapidity-odd with a rapidity slope at mid-rapidity, dv3/dy|(y=0), opposite in sign compared to the slope for directed flow. No significant v3 signal is observed for charged pions and kaons. Comparisons with models suggest that a mean field potential is required to describe these results, and that the triangular shape of the participant nucleons is the result of stopping and nuclear geometry.
The STAR Collaboration presents measurements of the semi-inclusive distribution of charged-particle jets recoiling from energetic direct-photon γdir and neutral-pion (π0) triggers in p+p and central Au+Au collisions at sNN−−−√=200 GeV over a broad kinematic range, for jet resolution parameters R=0.2 and 0.5. Medium-induced jet yield suppression is observed to be larger for R=0.2 than for 0.5, reflecting the angular range of jet energy redistribution due to quenching. The magnitude of suppression is similar for γdir- and π0-triggered data, which constrains the color-charge and path-length dependence of jet quenching. Theoretical model calculations incorporating jet quenching do not fully describe the measurements.
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.
Flow coefficients (v2 and v3) are measured in high-multiplicity p+Au, d+Au, and 3He+Au collisions at a center-of-mass energy of √sNN = 200 GeV using the STAR detector. The measurements are conducted using two-particle correlations with a pseudorapidity requirement of |η|< 0.9 and a pair gap of |Δη|>1.0. The primary focus of this paper is on the analysis procedures and methods employed, especially the subtraction of non-flow contributions. Four well-established non-flow subtraction methods are applied to determine vn, and their validity is verified using the HIJING event generator. The vn values are compared across the three collision systems at similar multiplicities, which allows for cancellation of final state effects and isolation of the impact of the initial geometry. While the v2 values display differences among these collision systems, the v3 values are largely similar, consistent with the expectations of subnucleon fluctuations in the initial geometry. The ordering of vn differs quantitatively from previous measurements obtained using two-particle correlations with a larger rapidity gap; this difference could be partially attributed to the effects of flow decorrelations in the rapidity direction.
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 measurement of exclusive J/ψ photoproduction in Au+Au ultra-peripheral collisions at sNN−−−√=200 GeV using the STAR detector. For the first time, i) the rapidity correlation between J/ψ photoproduction and neutron emission from nuclear breakups has been experimentally measured; ii) nuclear suppression factors are measured for both the coherent and incoherent J/ψ production. At photon-nucleon center-of-mass energy of 25.0 GeV, the coherent and incoherent J/ψ cross sections of Au nuclei are found to be 71±10% and 36±7%, respectively, of that of free protons. The stronger suppression observed in the incoherent production provides a new experimental handle to study the initial-state parton density in heavy nuclei. Data are compared with theoretical models quantitatively.
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 measurement of exclusive J/ψ photoproduction in Au+Au ultra-peripheral collisions at sNN−−−√=200 GeV using the STAR detector. For the first time, i) the rapidity correlation between J/ψ photoproduction and neutron emission from nuclear breakups has been experimentally measured; ii) nuclear suppression factors are measured for both the coherent and incoherent J/ψ production. At photon-nucleon center-of-mass energy of 25.0 GeV, the coherent and incoherent J/ψ cross sections of Au nuclei are found to be 71±10% and 36±7%, respectively, of that of free protons. The stronger suppression observed in the incoherent production provides a new experimental handle to study the initial-state parton density in heavy nuclei. Data are compared with theoretical models quantitatively.
Measurements of exclusive J/ψ, ψ(2s), and electron-positron (e+e−) pair photoproduction in Au+Au ultra-peripheral collisions are reported by the STAR experiment at √sNN=200 GeV. We report several first measurements at the Relativistic Heavy-Ion Collider, which are i) J/ψ photoproduction with large momentum transfer up to 2.2 (GeV/c)2, ii) coherent J/ψ photoproduction associated with neutron emissions from nuclear breakup, iii) the rapidity dependence of incoherent J/ψ photoproduction, iv) the ψ(2s) photoproduction cross section at mid-rapidity, and v) e+e− pair photoproduction up to high invariant mass of 6 GeV/c2. For measurement ii), the coherent J/ψ total cross section of γ∗+Au→J/ψ+Au as a function of the center-of-mass energy Wγ∗N has been obtained without photon energy ambiguities. The data are quantitatively compared with the Monte Carlo models STARlight, Sartre, BeAGLE, and theoretical calculations of gluon saturation with color glass condensate, nuclear shadowing with leading twist approximation, Quantum Electrodynamics, and the Next-to-Leading Order perturbative QCD. At the photon-nucleon center-of-mass energy of 25.0 GeV, the coherent and incoherent J/ψ cross sections of Au nuclei are found to be 71±10% and 36±7%, respectively, of that of free protons. These data provide an important experimental constraint for nuclear parton distribution functions and a unique opportunity to advance the understanding of the nuclear modification effect at the top RHIC energy.
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.
For the search of the chiral magnetic effect (CME), STAR previously presented the results from isobar collisions (9644Ru+9644Ru, 9640Zr+9640Zr) obtained through a blind analysis. The ratio of results in Ru+Ru to Zr+Zr collisions for the CME-sensitive charge-dependent azimuthal correlator (Δγ), normalized by elliptic anisotropy (v2), was observed to be close to but systematically larger than the inverse multiplicity ratio. The background baseline for the isobar ratio, Y=(Δγ/v2)Ru(Δγ/v2)Zr, is naively expected to be (1/N)Ru(1/N)Zr; however, genuine two- and three-particle correlations are expected to alter it. We estimate the contributions to Y from those correlations, utilizing both the isobar data and HIJING simulations. After including those contributions, we arrive at a final background baseline for Y, which is consistent with the isobar data. We extract an upper limit for the CME fraction in the Δγ measurement of approximately 10% at a 95% confidence level on in isobar collisions at sNN−−−√=200 GeV.
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.
The differential cross section for Z0 production, measured as a function of the boson's transverse momentum (pT), provides important constraints on the evolution of the transverse momentum dependent parton distribution functions (TMDs). The transverse single spin asymmetry (TSSA) of the Z0 is sensitive to one of the polarized TMDs, the Sivers function, which is predicted to have the opposite sign in p+p →W/Z+X from that which enters in semi-inclusive deep inelastic scattering. In this Letter, the STAR Collaboration reports the first measurement of the Z0/γ∗ differential cross section as a function of its pT in p+p collisions at a center-of-mass energy of 510 GeV, together with the Z0/γ∗ total cross section. We also report the measurement of Z0/γ∗ TSSA in transversely polarized p+p collisions at 510 GeV.
We report a new measurement of transverse single-spin asymmetries for dijet production in collisions of polarized protons at s√ = 200 GeV. Possible correlations between the proton spin and the transverse momenta of its partons, mutually orthogonal, with each perpendicular to the proton momentum direction, are probed at high Q2 ≈160 GeV2. The associated Sivers observable ⟨kT⟩, the average parton transverse momentum, is extracted using simple kinematics. Nonzero Sivers effects are observed for the first time in proton-proton collisions, but only when the jets are sorted by their net charge, which enhances the u- or d-quark contributions to separate data samples. This also enables a determination of the individual partonic contributions to the observed asymmetries.
We report the first measurements of cumulants, up to 4th order, of deuteron number distributions and proton-deuteron correlations in Au+Au collisions recorded by the STAR experiment in phase-I of Beam Energy Scan (BES-I) program at the Relativistic Heavy Ion Collider (RHIC). Deuteron cumulants, their ratios, and proton-deuteron mixed cumulants are presented for different collision centralities covering a range of center of mass energy per nucleon pair sNN−−−√ = 7.7 to 200 GeV. It is found that the cumulant ratios at lower collision energies favor a canonical ensemble over a grand canonical ensemble in thermal models. An anti-correlation between proton and deuteron multiplicity is observed across all collision energies and centralities, consistent with the expectation from global baryon number conservation. The UrQMD model coupled with a phase-space coalescence mechanism qualitatively reproduces the collision-energy dependence of cumulant ratios and proton-deuteron correlations.
The Ξ0 asymmetry parameters are measured using entangled quantum Ξ0 − Ξ¯ 0 pairs from a sample of ð448.1 2.9Þ × 106 ψð3686Þ events collected with the BESIII detector at BEPCII. The relative phase between the transition amplitudes of the Ξ0Ξ¯ 0 helicity states is measured to be ΔΦ ¼ −0.050 0.150 0.020 rad, which implies that there is no obvious polarization at the current level of statistics. The decay parameters of the Ξ0 hyperon ðαΞ0 ; αΞ¯ 0 ; ϕΞ0 ; ϕΞ¯ 0 Þ and the angular distribution parameter ½αψð3686Þ and ΔΦ are measured simultaneously for the first time. In addition, the CP asymmetry observables are determined to be AΞ0 CP ¼ ðαΞ0 þ αΞ¯ 0 Þ=ðαΞ0 − αΞ¯ 0 Þ ¼ −0.007 0.082 0.025 and ΔϕΞ0 CP ¼ ðϕΞ0 þ ϕΞ¯ 0 Þ=2 ¼ −0.079 0.082 0.010 rad, which are consistent with CP conservation.
Based on (10.09±0.04)×109 J/ψ events collected with the BESIII detector operating at the BEPCII collider, a partial wave analysis of the decay J/ψ→ϕπ0η is performed. We observe for the first time two new structures on the ϕη invariant mass distribution, with statistical significances of 24.0σ and 16.9σ; the first with JPC = 1+−, mass M = (1911 ± 6 (stat.) ± 14 (sys.))~MeV/c2, and width Γ= (149 ± 12 (stat.) ± 23 (sys.))~MeV, the second with JPC = 1−−, mass M = (1996 ± 11 (stat.) ± 30 (sys.))~MeV/c2, and width Γ = (148 ± 16 (stat.) ± 66 (sys.))~MeV. These measurements provide important input for the strangeonium spectrum. In addition, the f0(980)−a0(980)0 mixing signal in J/ψ→ϕf0(980)→ϕa0(980)0 and the corresponding electromagnetic decay J/ψ→ϕa0(980)0 are measured with improved precision, providing crucial information to understand the nature of a0(980)0 and f0(980).
Using an 𝑒+𝑒− collision data sample of (27.08±0.14)×108 𝜓(3686) events collected by the BESIII detector, we report the first observation of 𝜒𝑐𝐽→Ω−¯Ω+ (𝐽=0, 1, 2) decays with significances of 5.6𝜎, 6.4𝜎, and 18𝜎, respectively, where the 𝜒𝑐𝐽 mesons are produced in the radiative 𝜓(3686) decays. The branching fractions are determined to be ℬ(𝜒𝑐0→Ω−¯Ω+) = (3.51±0.54±0.29)×10−5, ℬ(𝜒𝑐1→Ω−¯Ω+)=(1.49±0.23±0.10)×10−5, and ℬ(𝜒𝑐2→Ω−¯Ω+)=(4.52±0.24±0.18)×10−5, where the first and second uncertainties are statistical and systematic, respectively.
The sympathetic nervous system (SNS) is a major regulatory mediator connecting the brain and the immune system that influences accordingly inflammatory processes within the entire body. In the periphery, the SNS exerts its effects mainly via its neurotransmitters norepinephrine (NE) and epinephrine (E), which are released by peripheral nerve endings in lymphatic organs and other tissues. Depending on their concentration, NE and E bind to specific α- and β-adrenergic receptor subtypes and can cause both pro- and anti-inflammatory cellular responses. The co-transmitter neuropeptide Y, adenosine triphosphate, or its metabolite adenosine are also mediators of the SNS. Local pro-inflammatory processes due to injury or pathogens lead to an activation of the SNS, which in turn induces several immunoregulatory mechanisms with either pro- or anti-inflammatory effects depending on neurotransmitter concentration or pathological context. In chronic inflammatory diseases, the activity of the SNS is persistently elevated and can trigger detrimental pathological processes. Recently, the sympathetic contribution to mild chronic inflammatory diseases like osteoarthritis (OA) has attracted growing interest. OA is a whole-joint disease and is characterized by mild chronic inflammation in the joint. In this narrative article, we summarize the underlying mechanisms behind the sympathetic influence on inflammation during OA pathogenesis. In addition, OA comorbidities also accompanied by mild chronic inflammation, such as hypertension, obesity, diabetes, and depression, will be reviewed. Finally, the potential of SNS-based therapeutic options for the treatment of OA will be discussed.
The main focus of this thesis is the application of the nonperturbative Functional Renormalization Group (FRG) to the study of low-energies effective models for Quantum Chromodynamics (QCD). The study of effective field theories and models is crucial for our understanding of physics, especially when we deal with fundamental interaction theories like QCD. In particular, the ultimate goal is the understanding of the critical properties of these models in such a way that we can have an insight on the actual critical phenomena of QCD, with a special focus on its chiral phase transition. The choice of the FRG method derives from the fact that it belongs to the class of functional non-perturbative methods and has also the advantage of linking physics at different energy scales. These features make FRG perfectly compatible with the task of studying non-perturbative phenomena and in particular phase transitions, like the ones expected for strongly interacting matter. However, the functional nature of the FRG approach and of the Wetterich equation has a consequence that its exact resolution is hardly possible, and an ansatz for the effective action is generally needed. In this work we choose to adopt the local-potential approximation (LPA), which prescribes to stop at zeroth order in the expansion in derivative operators of the quantum effective action, including only the quantum effective potential. In this work we exploited the key observation that the FRG flow equation can be cast, for specific models and truncation schemes, in the form of an advection-diffusion, possibly with a source term. This type of equation belongs to the class of problems faced in the context of viscous hydrodynamics. Therefore, an innovative approach to the solution of the FRG flow equation consists in the choice of a method developed specifically for the resolution of this class of hydrodynamic equations. In particular, the Kurganov-Tadmor finite-volume scheme is adopted. Throughout this work we apply this scheme to the study of different physical systems, showing the reliability and the flexibility of this approach.
In the first part of the thesis, we discuss the well-known O(N) model, using the hydrodynamic formulation to solve the FRG flow equation in the LPA truncation. We focus on the study of the critical behaviour of the system and calculate the corresponding critical exponents. Particular attention is given to the error estimation in the extraction of critical exponents, which is a needed and not widely explored aspect. The results are well compatible with others in the literature, obtained with different perturbative and nonperturbative methods, which validates the procedure. In the second part of the thesis, we introduce the quark-meson model as a low-energy effective model for QCD, with a specific focus on its chiral symmetry-breaking pattern and the subsequent dynamical quark-mass generation. The LPA flow equation is of the advection-diffusion type, with an extra source contribution which is due to the inclusion of fermionic degrees of freedom. We thus adopt the developed numerical techniques to derive the phase diagram of the model, which is in agreement with the one obtained with other techniques in the literature.
We also follow another possible way for the study of the critical properties of the quark-meson model: the so-called thermodynamic geometry. This approach is based on the interpretation of the parameter space of the system as a differential manifold. One can then obtain relevant information about the phase transitions from the Ricci scalar. We studied the chiral crossover investigating the behavior of the Ricci scalar up to the critical point, featuring a peaking behavior in the presence of the crossover. We then repeated this analysis in the chiral limit, where the phase transition is expected to be of second order. Via this geometric technique it is possible to have a different view on the chiral phase transition of QCD. This is the case since this approach is based on the calculation of quantities which are influenced by higher-order momenta of the thermodynamic potential, thus allowing for a more comprehensive analysis of the phase transition.
Finally, we exploit the numerical advancement to face the issue of the regulator choice in the FRG calculations. This is one of the most delicate issues which arise when using approximations to solve the FRG flow equation and deserves extensive investigation. In particular, we performed a vacuum parameter study and used the RG consistency requirement to determine the impact of the choice of the regulator on the physical observables and on the phase diagram of the model. Via this study we develop a systematic method to comparison the results obtained via different regulators. We show the importance of the choice of an appropriate UV cutoff in the determination of UV-independent IR observables and, consequently, the impact on the latter that the truncation of the effective average action and the choice of the regulator have.
The financial sector plays an important role in financing the green transformation. Various regulatory initiatives in the EU aim to improve transparency in relation to the sustainability of financial products and the sustainability of economic activities of non-financial and financial undertakings. For credit institutions, the Green Asset Ratio (GAR) has been established by the European regulatory authorities as a key performance indicator (KPI) for measuring the proportion of Taxonomy-aligned on-balance-sheet exposure in relation to the total assets. The breakdown of the total GAR by type of counterparty, environmental objective and type of asset provides in-depth information about the sustainability profile of a credit institution. This information, which has not been available to date, may also initiate discussions between management and shareholders or other stakeholders regarding the future sustainability strategy of credit institutions. This paper provides an overview of the regulatory background and the method of calculating the GAR along different dimensions. Finally, the potential benefits and limitations of the GAR are discussed.
We analyze the experimental data on nuclei and hypernuclei yields recently obtained by the STAR collaboration. The hybrid dynamical and statistical approaches which have been developed previously are able to describe the experimental data reasonably. We discuss the intriguing difference between the yields of normal nuclei and hypernuclei which may be related to the properties of hypermatter at subnuclear densities. Most importantly new (hyper-)nuclei could be detected via particle correlations, and such measurements are relevant to pin down the production mechanism.
Objectives: Within the tertiary-case database, the authors tested for differences in long-term continence rates (≥ 12 months) between prostate cancer patients with extraprostatic vs. organ-confined disease who underwent Robotic-Assisted Radical Prostatectomy (RARP).
Method: In the institutional tertiary-care database the authors identified prostate cancer patients who underwent RARP between 01/2014 and 01/2021. The cohort was divided into two groups based on tumor extension in the final RARP specimen: patients with extraprostatic (pT3/4) vs. organ-confined (pT2) disease. Additionally, the authors conducted subgroup analyses within both the extraprostatic and organ-confined disease groups to compare continence rates before and after the implementation of the new surgical technique, which included Full Functional-Length Urethra preservation (FFLU) and Neurovascular Structure-Adjacent Frozen-Section Examination (NeuroSAFE). Multivariable logistic regression models addressing long-term continence were used.
Results: Overall, the authors identified 201 study patients of whom 75 (37 %) exhibited extraprostatic and 126 (63 %) organ-confined disease. There was no significant difference in long-term continence rates between patients with extraprostatic and organ-confined disease (77 vs. 83 %; p = 0.3). Following the implementation of FFLU+ NeuroSAFE, there was an overall improvement in continence from 67 % to 89 % (Δ = 22 %; p < 0.001). No difference in the magnitude of improved continence rates between extraprostatic vs. organ-confined disease was observed (Δ = 22 % vs. Δ = 20 %). In multivariable logistic regression models, no difference between extraprostatic vs. organ-confined disease in long-term continence was observed (Odds Ratio: 0.91; p = 0.85).
Conclusion: In this tertiary-based institutional study, patients with extraprostatic and organ-confined prostate cancer exhibited comparable long-term continence rates.
Improved measurement of the branching fractions of the inclusive decays D⁺ → Kₛ⁰X and D⁰ → Kₛ⁰X
(2023)
By analyzing 2.93 fb−1 of 𝑒+𝑒− collision data taken at the center-of-mass energy of 3.773 GeV with the BESIII detector, the branching fractions of the inclusive decays 𝐷+→𝐾0 𝑆𝑋 and 𝐷0→𝐾0 𝑆𝑋 are measured to be (33.11±0.13±0.36)% and (20.75±0.12±0.20)%, respectively, where the first uncertainties are statistical and the second are systematic. These results are consistent with the world averages of previous measurements, but with much improved precision.
We compute the critical exponents of the O(N) model within the Functional Renormalization Group (FRG) approach. We use recent advances which are based on the observation that the FRG flow equation can be put into the form of an advection-diffusion equation. This allows to employ well-tested hydrodynamical algorithms for its solution. In this study we work in the local potential approximation (LPA) for the effective average action and put special emphasis on estimating the various sources of errors. Our results complement previous results for the critical exponents obtained within the FRG approach in LPA. Despite the limitations imposed by restricting the discussion to the LPA, the results compare favorably with those obtained via other methods.
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.
The STAR experiment at RHIC reports new measurements of jet quenching based on the semi-inclusive distribution of charged-particle jets recoiling from direct photon (γdir) and neutral pion (π0) triggers in p+p and central Au+Au collisions at √sNN=200 GeV, for triggers in the range 9<EtrigT<20 GeV. The datasets have integrated luminosities of 3.9 nb−1 for Au+Au and 23 pb−1 for p+p collisions. Jets are reconstructed using the anti-kT algorithm with resolution parameters R=0.2 and 0.5. The large uncorrelated jet background in central Au+Au collisions is corrected using a mixed-event approach, which enables precise charged-particle jet measurements at low transverse momentum pchT,jet and large R. Recoil-jet distributions are reported in the range pchT,jet<25 GeV. Comparison of the distributions measured in p+p and Au+Au collisions reveals strong medium-induced jet yield suppression for R=0.2, with markedly less suppression for R=0.5. These data provide new insight into the mechanisms underlying jet quenching, and the angular dependence of medium-induced jet-energy transport.
A Large Ion Collider Experiment (ALICE) is a high-energy physics experiment, designed to study heavy ion collisions at the European Organization for Nuclear Research (CERN)Large Hadron Collider (LHC). ALICE is built to study the fundamental properties of matter as it existed shortly after the big bang. This requires reading out millions of sensors with high frequency, enabling high statistics for physics analysis, resulting in a considerable computing demand concerning network throughput and processing power. With the ALICE Run 3 upgrade [14], requirements for a High Throughput Computing
(HTC) online processing cluster increased significantly, due to more than an order of magnitude more data than in Run 2, resulting in a processing input rate of up to 900 GB/s. Online (real-time) event reconstruction allows for the compression of the data stream to 130 GB/s, which is stored on disk for physics analysis.
This thesis presents the implementation of the ALICE Event Processing Node (EPN) compute farm, to cope with the Run 3 online computing challenges. Building a Data Centre tailored to ALICE requirements for the Run 3 and Run 4 EPN farm. Providing the operational conditions for a dynamic compute environment of a High Performance Computing (HPC) cluster, with significant load changes in a short time span, when starting or stopping a data-taking run. EPN servers provide the required computing resources for online reconstruction and data compression. The farm includes network connectivity towards First Level Processors (FLPs), requiring reliable throughput of 900 GB/s between FLPs and EPNs and connectivity from the internal InfiniBand network to the CERN Exabyte Object Storage (EOS) Ethernet network, with more than 100 GB/s.
The results of operating the EPN computing infrastructure during the first year of Run 3 LHC collisions are described in the context of the ALICE experiment. The EPN farm was delivering the expected performance for ALICE data-taking. Data Centre environmental conditions remained stable during the last more than two years, in particular during starting and stopping runs, which include significant changes in IT load. Several unforeseen external circumstances lead to increasing demands for the Online Offline System (O2). Higher data rates than anticipated required network performance to exceed the initial design specifications, for the throughput between FLPs and EPNs. In particular, the high throughput from an internal EPN InfiniBand network towards the storage Ethernet network was one of the challenges to overcome.
Using e+e− annihilation data corresponding to an integrated luminosity of 2.93 fb−1 taken at the center-of-mass energy s√=3.773~GeV with the BESIII detector, a joint amplitude analysis is performed on the decays D0→π+π−π+π− and D0→π+π−π0π0(non-η). The fit fractions of individual components are obtained, and large interferences among the dominant components of D0→a1(1260)π, D0→π(1300)π, D0→ρ(770)ρ(770) and D0→2(ππ)S are found in both channels. With the obtained amplitude model, the CP-even fractions of D0→π+π−π+π− and D0→π+π−π0π0(non-η) are determined to be (75.2±1.1stat.±1.5syst.)% and (68.9±1.5stat.±2.4syst.)%, respectively. The branching fractions of D0→π+π−π+π− and D0→π+π−π0π0(non-η) are measured to be (0.688±0.010stat.±0.010syst.)% and (0.951±0.025stat.±0.021syst.)%, respectively. The amplitude analysis provides an important model for binning strategy in the measurements of the strong phase parameters of D0→4π when used to determine the CKM angle γ(ϕ3) via the B−→DK− decay.
Improved measurement of the branching fractions of the inclusive decays D⁺ → Kₛ⁰X and D⁰ → Kₛ⁰X
(2023)
By analyzing 2.93 fb−1 of e+e− collision data taken at the center-of-mass energy of 3.773 GeV with the BESIII detector, the branching fractions of the inclusive decays D+→K0SX and D0→K0SX are measured to be (32.78±0.13±0.27)% and (20.54±0.12±0.18)%, respectively, where the first uncertainties are statistical and the second are systematic. These results are consistent with the world averages of previous measurements, but with improved precision.
Based on 7.33 fb−1 of e+e− collision data collected at center-of-mass energies between 4.128 and 4.226 GeV with the BESIII detector, the experimental studies of the doubly Cabibbo-suppressed decays D+s→K+K+π− and D+s→K+K+π−π0 are reported. We determine the absolute branching fraction of D+s→K+K+π− to be (1.23+0.28−0.25(stat)±0.06(syst)) ×10−4. No significant signal of D+s→K+K+π−π0 is observed and the upper limit on its decay branching fraction at 90\% confidence level is set to be 1.7×10−4.
Using a data sample of (1.0087±0.0044)×1010 J/ψ decay events collected with the BESIII detector at the center-of-mass energy of s√=3.097 GeV, we present a search for the hyperon semileptonic decay Ξ0→Σ−e+νe which violates the ΔS=ΔQ rule. No significant signal is observed, and the upper limit on the branching fraction B(Ξ0→Σ−e+νe) is determined to be 1.6×10−4 at the 90% confidence level. This result improves the previous upper limit result by about one order of magnitude.
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.
The thermodynamic properties of the interacting particle–antiparticle boson system at high temperatures and densities were investigated within the framework of scalar and thermodynamic mean-field models. We assume isospin (charge) density conservation in the system. The equations of state and thermodynamic functions are determined after solving the self-consistent equations. We study the relationship between attractive and repulsive forces in the system and the influence of these interactions on the thermodynamic properties of the bosonic system, especially on the development of the Bose–Einstein condensate. It is shown that under “weak” attraction, the boson system has a phase transition of the second order, which occurs every time the dependence of the particle density crosses the critical curve or even touches it. It was found that with a “strong” attractive interaction, the system forms a Bose condensate during a phase transition of the first order, and, despite the finite value of the isospin density, these condensate states are characterized by a zero chemical potential. That is, such condensate states cannot be described by the grand canonical ensemble since the chemical potential is involved in the conditions of condensate formation, so it cannot be a free variable when the system is in the condensate phase.
We compute the critical exponents of the O(N) model within the Functional Renormalization Group (FRG) approach. We use recent advances which are based on the observation that the FRG flow equation can be put into the form of an advection-diffusion equation. This allows to employ well-tested hydrodynamical algorithms for its solution. In this study we work in the local potential approximation (LPA) for the effective average action and put special emphasis on estimating the various sources of errors. Our results complement previous results for the critical exponents obtained within the FRG approach in LPA. Despite the limitations imposed by restricting the discussion to the LPA, the results compare favorably with those obtained via other methods.
We reanalyze some critical exponents of the 𝑂(𝑁) model within the functional renormalization group (FRG) approach in the local potential approximation (LPA). We use recent advances which are based on the observation that the FRG flow equation in LPA can be put into the form of an advection-diffusion equation. This allows to employ well-tested hydrodynamical algorithms for its solution to better estimate various sources of errors. Our results complement previous results for the critical exponents obtained within the FRG approach in LPA and compare favorably with those obtained via other methods.
The raccoon is listed among the invasive alien species of EU concern requiring management actions. Projections of its global distribution have been mainly based on climatic variables so far. In this study, we aim to address the impact of land cover (LC) on the raccoon distribution in North America and Europe. First, we identified the LC types in which the observation sites are predominantly located to derive preferred LC types. Second, we used an ecological niche modelling (ENM) approach to evaluate the predictive power of climatic and LC information on the current distribution patterns of raccoons in both ranges. Raccoons seem to be more often associated to forested areas and mixed landscapes, including cropland and urban areas, but underrepresented in vegetation-poor areas, with patterns largely coinciding in both ranges. In order to compare the predictive power of climate variables and land cover variables, we conducted principal component analyses of all variables in the respective variable sets (climate variables and land cover variables) and used all PC variables that together explain 90% of the total variance in the respective set as predictors. Land cover only models resulted in patchy patterns in the projected habitat suitabilities and showed a higher performance compared to the climate only models in both ranges. In Europe, the land cover habitat suitability seems to exceed the current observed occurrences, which could indicate a further spread potential of the raccoon in Europe. We conclude that information on land cover types are important drivers, which explain well the spatial patterns of the raccoon. Consideration of land cover could benefit efforts to control invasive carnivores and contribute to better management of biodiversity, but also human and animal health.
The cosmological implications of the Covariant Canonical Gauge Theory of Gravity (CCGG) are investigated. CCGG is a Palatini theory derived from first principles using the canonical transformation formalism in the covariant Hamiltonian formulation. The Einstein-Hilbert theory is thereby extended by a quadratic Riemann-Cartan term in the Lagrangian. Moreover, the requirement of covariant conservation of the stress-energy tensor leads to necessary presence of torsion. In the Friedman universe that promotes the cosmological constant to a time-dependent function, and gives rise to a geometrical correction with the EOS of dark radiation. The resulting cosmology, compatible with the ΛCDM parameter set, encompasses bounce and bang scenarios with graceful exits into the late dark energy era. Testing those scenarios against low-z observations shows that CCGG is a viable theory.
Graphium chironides malayanum Eliot, 1982 was described as a taxon occurring sympatrically with G. bathycles bathycloides in Peninsular Malaysia. However, the validity of the subspecies has been questioned in a recent publication that was based on a study of DNA and morphology, implying that G. c. malayanum is a synonym of G. b. bathycloides and G. chironides is absent from the Peninsula. A re-examination of male wing morphology, genitalia and DNA shows that G. c. malayanum is a valid taxon distinguished from G. b. bathycloides by wider discal markings, a less falcate forewing, distinct differences in the arms of the harpe in the male genitalia and clearly divergent mtDNA COI genes. In the DNA analysis, G. c. malayanum formed a monophyletic clade closely related to G. chironides from China, and both were well-separated from the G. b. bathycloides clade. An examination of characters used in the previous study showed that the conclusions reached were due to misinterpretation of diagnostic characters, misidentification of specimens and the absence of G. c. malayanum among the specimens examined. When these characters were correctly interpreted, each specimen was readily assigned to the correct taxon. Diagnostic morphological characters are reclarified based on the current data.
Two new species of terrestrial isopods are described from iron ore caves in Brazil, within the Amazon biome, Circoniscus mendesi López-Orozco, Campos-Filho & Bichuette sp. nov. and C. xikrin López-Orozco, Campos-Filho & Carpio-Díaz sp. nov. (Scleropactidae). In addition, the knowledge of the distribution of Ctenorillo ferrarai Campos-Filho, Araujo & Taiti, 2014 (Armadillidae) is extended to Parauapebas, and Benthanoides tarzan Cardoso & Ferreira, 2023 to south area of the Campos Ferruginosos National Park, both in the State of Pará. Moreover, a distribution map and photographs of the species are given.
Three new species of Loxosceles Heinecken & Lowe, 1832 (Araneae, Sicariidae) from Brazilian caves
(2024)
Three new species of recluse spiders are described from Brazilian caves with both males and females. Loxosceles boqueirao Bertani & Gallão sp. nov. is found in the State of Bahia, in the Serra do Ramalho karst area, it belongs to the rufescens species group, and is closely related to L. cardosoi Bertani, von Schimonsky & Gallão, 2018 and L. carinhanha Bertani, von Schimonsky & Gallão, 2018 from the same karst area. Thus, there are now three species in the Serra do Ramalho karst area closely related, but noticeably distinct morphologically from other species of Loxosceles. Loxosceles planetaria Bertani & Gallão sp. nov. and L. bodoquena Bertani & Gallão sp. nov. are found in the State of Mato Grosso do Sul, in the Serra da Bodoquena karst area. They belong to the gaucho species group and are closely related to L. gaucho Gertsch, 1967. These are the first species of Loxosceles described from this karst area in the State of Mato Grosso do Sul. Loxosceles boqueirao sp. nov. and L. bodoquena sp. nov. bear some troglomorphisms and are, herein, proposed as troglobitic species, whereas L. planetaria sp. nov. is proposed as a troglophilic species. Brazil has now 22 described species of Loxosceles.
The remarkable sharpshooter Prodigiella silvanoi gen. et sp. nov. is described and illustrated (including the external form, color, male and female terminalia) from the Atlantic Forest of southern and southeastern Brazil (states of Paraná and Rio de Janeiro). The new genus can be distinguished from other Neotropical genera of the Cicadellini by a combination of various morphological features, including an asymmetrical aedeagus with a bifid shaft and peculiar basal and apical processes and ovipositor valvula II distinctly expanded beyond basal curvature, its dorsal margin with 35–40 teeth, and ventral margin without preapical prominence. A discussion comparing Prodigiella with superficially similar taxa of the genera Macugonalia Young, 1977, Ruppeliana Young, 1977, and Versigonalia Young, 1977 is provided. The discovery of this peculiar new genus indicates that much collecting work in the remaining parts of the Atlantic Forest is clearly and urgently needed.
Widely distributed phoretic blister beetles usually display unstructured geographic patterns of genetic diversity within species, resulting from recurrent long-dispersal events across their range. To investigate the extent of this pattern in the phoretic genus Lampromeloe, and particularly in western Mediterranean and European populations of L. variegatus, we performed: (1) a phylogeographic analysis based on fragments of the mitochondrial genes COI and 16S, and (2) a morphological revision based on qualitative and morphometric traits. Two allopatric lineages were recovered within L. variegatus, one distributed across Europe and the other in North Africa. These lineages are readily distinguishable based on morphological traits. We conclude that these lineages constitute two diagnosable evolutionary units and, consequently, we describe the North African populations as a new species, Lampromeloe pantherinus sp. nov. The new species is closely related to L. variegatus, from which it differs mainly by the elytral macrosculpture and by the shape of male genitalia. The elytral macrosculpture of L. pantherinus is somewhat similar to that of L. cavensis, a species widely distributed in the lowlands of the Mediterranean Basin. However, these two non-sister species can be distinguished by the morphology and macrosculpture of the pronotum and by the shape of the male genitalia.
The first sawfly from the Oligocene of Céreste (Southern France (Hymenoptera: Tenthredinidae)
(2024)
Luberotenthredo cerestensis gen. et sp. nov. is the first record of the sawfly family Tenthredinidae from the Oligocene of Céreste (Southern France). This taxon is described and illustrated based on a well-preserved specimen. This genus resembles the extant genus Perineura (subfamily Tenthredininae, tribe Perineurini) with which it shares forewing venation similarities and numerous morphological characters. This new taxon is the first fossil representative of the tribe Perineurini and can be used as a calibration point for future investigation of the diversification of the family Tenthredinidae.
The koinobiont endoparasitoid genus Triraphis Ruthe, 1855 (Rogadinae Foerster, 1863) is a group of braconid wasps that contains 74 species distributed along the Nearctic, Neotropical, Oriental and Palearctic regions. We amplified a fragment of the cytochrome oxidase subunit I (COI) for 19 specimens of Triraphis from the Chamela Biological Station (CBS), a region mainly composed of tropical dry forest near the Pacific coast of Jalisco, Mexico. Based on genetic distances among specimens of Triraphis from the CBS and all COI sequences of BINs assigned to Triraphis and Rogas Nees, 1819 available in the BOLDSYSTEMS database, we identified three clusters in the CBS that correspond with T. bradzlotnicki Sharkey, 2021, T. davidwahli Sharkey, 2021 and T. defectus Valerio, 2015, which were previously described from Costa Rica. Based on morphology, we identified individuals of T. fusciceps Cresson, 1869 and provided COI sequences of this species for the first time. Four genetic clusters of Triraphis correspond to four new species that are described here: T. kardia sp. nov., T. ocellatus sp. nov., T. divergens sp. nov. and T. luzabrilae sp. nov. Since T. bradzlotnicki and T. davidwahli were exclusively described with molecular data (COI), we morphologically described them based on Mexican specimens.
Palaeosphryon menatensis gen. et sp. nov., first unambiguous representative of the longhorn beetle subfamily Prioninae from the Paleocene of Menat (France), is described and illustrated. The new fossil is placed into the tribe Prionini, showing some similarities with some species of the extant genera Osphryon (Papua New Guinea) and Titanus (Brazil, Colombia, Guianas, Ecuador, Peru), viz. in general body shape, antennomere 3 as long as first and second together but shorter than the length of fourth plus fifth, elongate elytra, and small spines on the lateral margin of the pronotum disposed in a relatively similar way as in Osphryon. Nevertheless, the exact affinities of the new fossil within the Prionini remain uncertain because of the lack of a recent phylogenetic analysis in which it could be integrated. This fossil beetle is exceptional for its very large size, with a body 70 mm long. Some other large longhorn beetles have been found in the same outcrop, and are awaiting description. The positions of the previously described Cerambycidae from Menat are also discussed. This exceptional fauna of Cerambycidae is in accordance with the current palaeoenvironmental reconstruction for the Menat Konservat-Lagerstätte, as a small maar lake surrounded by a warm and humid, probably evergreen forest.
A new family of Cyphophthalmi with disjunct Mediterranean distribution, Parasironidae fam. nov., is proposed. The new family comprises four genera and seven species. Cimmerosiro gen. nov., Tirrenosiro gen. nov. and Ebrosiro gen. nov. are described as new genera, and Tirrenosiro axeli gen. et sp. nov., Cimmerosiro krivolutskyi gen. et sp. nov., C. juberthiei gen. et sp. nov. and C. rhodiensis gen. et sp. nov. as new species. Parasironidae stands out by a set of characteristics that we recognize as predominantly plesiomorphic. These characteristics and the present distribution indicate the great age of the family, probably early Mesosoic. We attribute its origin to the western part of the Cimmerian terrane, and its current distribution and diversification of the major clades to geotectonic events during the Mesozoic. Additionally, a new sensory organ (sensilla) has been discovered in Cyphophthalmi. This organ is located on the pedipalp coxae and is believed to have a potential hygroreceptive function.
The monotypic banchine ichneumonid genus Shortia is rediscovered after 39 years, based on two new species from India, far away from the type locality in Australia: S. karumban Ranjith sp. nov. and S. manjapulli Ranjith sp. nov., collected from the Western Ghats, India. The generic concept of Shortia is revised. Both new species and the type species of the genus, S. siccula Gauld, 1984, are illustrated. A taxonomic key for the identification of species of Shortia is provided and the possible causes for the disjunct distribution are discussed.
The “trachystreptoform” species of Spirostreptidae, i.e., species which would formerly have been ascribed to the tribe Trachystreptini, from the Udzungwa Mountains are (re)described, including one new genus and five new species: Attemsostreptus reflexus Akkari & Enghoff, 2019, A. cataractae Enghoff sp. nov., A. leptoptilos Enghoff sp. nov., A. julostriatus Enghoff sp. nov., Lophostreptus tersus (Cook, 1896) (= L. ptilostreptoides Carl, 1909 syn. nov.), L. magombera Enghoff sp. nov., and Udzungwastreptus marianae Enghoff gen. et sp. nov. The type material of Lophostreptus regularis Attems, 1909 (= L. tersus) is discussed. The discussion includes paragraphs on the classification and the Udzungwa fauna of Spirostreptidae, on grouping of the Udzungwa trachystreptoform species in relation to altitude, and on the possibly recent immigration of A. reflexus and L. tersus into the Udzungwa Mts.
Known by many names, the Chinese banyan (Ficus microcarpa L.) is a monoecious plant species originating from south-eastern Asia which has been introduced as an ornamental in numerous areas outside its native range, including the Mediterranean. Like every species of Ficus, it is associated with a series of chalcid wasp species, known as fig wasps. These species are distributed in the families Agaonidae, Epichrysomallidae, Eurytomidae, Ormyridae and Pteromalidae. In this publication, we describe a new species of Ormyrus Westwood, 1832 (Hymenoptera, Chalcidoidea, Ormyridae), O. microcarpae Askew & Koutsoukos sp. nov., reared from figs of F. microcarpa collected from Greece and Cyprus. The new species is compared with O. lini and O. watshami. This species is likely to be a parasitoid of Meselatus bicolor Chen, 1999 (Hymenoptera, Epichrysomallidae). In addition, the previously unknown female of O. lini is also described and illustrated. This publication constitutes the first report of species of Ormyrus associated with figs in Europe.
Six species of the spider genus Spinirta Jin & Zhang, 2020 from southern China (Araneae: Corinnidae)
(2024)
In the current study, six species of the genus Spinirta from southern China are recognized, four new species are described: S. hongyui Wang, Lu & Z.S. Zhang sp. nov. (♂♀), S. liuae Wang, Lu & Z.S. Zhang sp. nov. (♂♀), S. simianshan Wang, Lu & Z.S. Zhang sp. nov. (♂♀) and S. yintiaoling Wang, Lu & Z.S. Zhang sp. nov. (♂). Females of S. aviforma Jin & Zhang, 2020 (♂♀) and S. quadrata Jin & Zhang, 2020 (♂♀) are described for the first time. Photos of the body and copulatory organs, as well as the locality map are provided.
The ammonoids of the family Maenioceratidae from Givetian sedimentary rocks of the Anti-Atlas (Morocco) are investigated. The study is based on new collections stored in the Museum für Naturkunde, Berlin. The genera Maenioceras Schindewolf, 1933 and Afromaenioceras Göddertz, 1987 are revised; the genus Trimaenioceras is newly described. The species Maenioceras afroterebratum sp. nov., Maenioceras mzerrebense sp. nov., Maenioceras oufranense sp. nov., Maenioceras beckeri sp. nov., Afromaenioceras sulcatostriatum (Bensaïd, 1974), Afromaenioceras hiemale sp. nov., Afromaenioceras bensaidi sp. nov., Afromaenioceras brumale sp. nov., Afromaenioceras crassum (Bensaïd, 1974), Trimaenioceras klugi gen. et sp. nov., Trimaenioceras eculeus gen. et sp. nov., Trimaenioceras fuscina gen. et sp. nov. and Trimaenioceras paucum gen. et sp. nov. are described in detail.
A remarkable morphologically and genetically distinct species of the genus Ero C.L. Koch, 1836 is described based on both sexes from the cloud forest of the island of Saint Helena: Ero lizae sp. nov. Another new species, Ero natashae sp. nov., is also described on the basis of morphological differences in the male and female genitalia. Both species were initially reported a single species, Ero aphana (Walckenaer, 1802), from the island by Unzicker (1977).
High resolution images are provided for type specimens of Platygastroidea (Hymenoptera: Apocrita) in the Hope Entomological Collections, Oxford University. We formally resurrect Trissoscelio Kieffer revised status to accommodate T. bifasciata (Dodd) new combination, T. indica (Mani) new combination, T. nigriceps Kieffer revised combination, T. ruficeps Kieffer revised combination, and T. punctaticeps Kieffer revised combination. Paridris subplana (Dodd) new combination is transferred from Sceliacantha Dodd to Paridris Kieffer and treated as a senior synonym of P. coorgensis Sharma.
ZooBank registration. urn:lsid:zoobank.org:pub:EB97FE10-B01D-4D45-AF6E-D247ED0040BE
Two new species and one new genus of Lamiinae (Coleoptera: Cerambycidae) are described in Acanthocinini: Embera flava new species, new genus, from Panama; and Nealcidion lingafelteri new species from Costa Rica. The species-group name of Nealcidion napoensis Nascimento and McClarin, 2018 is corrected and morphological variations in Leptostylus cristulatus Bates, 1872 are reported. Trypanidius mimicavus Carelli, Monné, and Souza, 2013 is redescribed and transferred to Carphina Bates, 1872, forming the new combination Carphina mimicavus. Colombicallia curta Galileo and Martins, 1992 (Calliini) is recorded from Panama for the first time.
ZooBank registration. urn:lsid:zoobank.org:pub:7DD2EF0F-7DC9-4A85-83DA-10F4EE8CA8CB