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Measurements of elliptic (v2) and triangular (v3) flow coefficients of π±, K±, p+p¯¯¯, K0S, and Λ+Λ¯¯¯¯ obtained with the scalar product method in Xe-Xe collisions at sNN−−−√ = 5.44 TeV are presented. The results are obtained in the rapidity range |y|<0.5 and reported as a function of transverse momentum, pT, for several collision centrality classes. The flow coefficients exhibit a particle mass dependence for pT<3 GeV/c, while a grouping according to particle type (i.e., meson and baryon) is found at intermediate transverse momenta (3< pT <8 GeV/c). The magnitude of the baryon v2 is larger than that of mesons up to pT = 6 GeV/c. The centrality dependence of the shape evolution of the pT-differential v2 is studied for the various hadron species. The v2 coefficients of π±, K±, and p+p¯¯¯ are reproduced by MUSIC hydrodynamic calculations coupled to a hadronic cascade model (UrQMD) for pT<1 GeV/c. A comparison with vn measurements in the corresponding centrality intervals in Pb-Pb collisions at sNN−−−√ = 5.02 TeV yields an enhanced v2 in central collisions and diminished value in semicentral collisions.
This article presents groomed jet substructure measurements in pp and Pb−Pb collisions at sNN−−−√=5.02 TeV with the ALICE detector. The Soft Drop grooming algorithm provides access to the hard parton splittings inside a jet by removing soft wide-angle radiation. We report the groomed jet momentum splitting fraction, zg, and the (scaled) groomed jet radius, θg. Charged-particle jets are reconstructed at midrapidity using the anti-kT algorithm with resolution parameters R=0.2 and R=0.4. In heavy-ion collisions, the large underlying event poses a challenge for the reconstruction of groomed jet observables, since fluctuations in the background can cause groomed parton splittings to be misidentified. By using strong grooming conditions to reduce this background, we report these observables fully corrected for detector effects and background fluctuations for the first time. A narrowing of the θg distribution in Pb−Pb collisions compared to pp collisions is seen, which provides direct evidence of the modification of the angular structure of jets in the quark−gluon plasma. No significant modification of the zg distribution in Pb−Pb collisions compared to pp collisions is observed. These results are compared with a variety of theoretical models of jet quenching, and provide constraints on jet energy-loss mechanisms and coherence effects in the quark−gluon plasma.
The production of J/ψ is measured at midrapidity (|y|<0.9) in proton-proton collisions at s√ = 5.02 and 13 TeV, through the dielectron decay channel, using the ALICE detector at the Large Hadron Collider. The data sets used for the analyses correspond to integrated luminosities of Lint = 19.4 ± 0.4 nb−1 and Lint = 32.2 ± 0.5 nb−1 at s√ = 5.02 and 13 TeV, respectively. The fraction of non-prompt J/ψ mesons, i.e. those originating from the decay of beauty hadrons, is measured down to a transverse momentum pT = 2 GeV/c (1 GeV/c) at s√ = 5.02 TeV (13 TeV). The pT and rapidity (y) differential cross sections, as well as the corresponding values integrated over pT and y, are carried out separately for prompt and non-prompt J/ψ mesons. The results are compared with measurements from other experiments and theoretical calculations based on quantum chromodynamics (QCD). The shapes of the pT and y distributions of beauty quarks predicted by state-of-the-art perturbative QCD models are used to extrapolate an estimate of the bb¯¯¯ pair cross section at midrapidity and in the total phase space. The total bb¯¯¯ cross sections are found to be σbb¯¯¯=541±45(stat.)±69(syst.)+10−12(extr.) μb and σbb¯¯¯ = 218±37(stat.)±31(syst.)+8.2−9.1(extr.) μb at s√ = 13 and 5.02 TeV, respectively. The value obtained from the combination of ALICE and LHCb measurements in pp collisions at s√ = 13 TeV is also provided.
Production of K0S, Λ (Λ), Ξ± and Ω± in jets and in the underlying event in pp and p–Pb collisions
(2022)
The production of strange hadrons (K0S, Λ, Ξ±, and Ω±), baryon-to-meson ratios (Λ/K0S, Ξ/K0S, and Ω/K0S), and baryon-to-baryon ratios (Ξ/Λ, Ω/Λ, and Ω/Ξ) associated with jets and the underlying event were measured as a function of transverse momentum (pT) in pp collisions at s√=13 TeV and p-Pb collisions at sNN−−−√=5.02 TeV with the ALICE detector at the LHC. The inclusive production of the same particle species and the corresponding ratios are also reported. The production of multi-strange hadrons, Ξ± and Ω±, and their associated particle ratios in jets and in the underlying event are measured for the first time. In both pp and p-Pb collisions, the baryon-to-meson and baryon-to-baryon yield ratios measured in jets differ from the inclusive particle production for low and intermediate hadron pT (0.6−6 GeV/c). Ratios measured in the underlying event are in turn similar to those measured for inclusive particle production. In pp collisions, the particle production in jets is compared with PYTHIA 8 predictions with three colour-reconnection implementation modes. None of them fully reproduces the data in the measured hadron pT region. The maximum deviation is observed for Ξ± and Ω±, which reaches a factor of about six. In p-Pb collisions, there is no significant event-multiplicity dependence for particle production in jets, in contrast to what is observed in the underlying event. The presented measurements provide novel constraints on hadronisation and its Monte Carlo description. In particular, they demonstrate that the fragmentation of jets alone is insufficient to describe the strange and multi-strange particle production in hadronic collisions at LHC energies.
Long non-coding RNAs are a very versatile class of molecules that can have important roles in regulating a cells function, including regulating other genes on the transcriptional level. One of these mechanisms is that RNA can directly interact with DNA thereby recruiting additional components such as proteins to these sites via a RNA:dsDNA triplex formation. We genetically deleted the triplex forming sequence (FendrrBox) from the lncRNA Fendrr in mice and find that this FendrrBox is partially required for Fendrr function in vivo. We find that the loss of the triplex forming site in developing lungs causes a dysregulation of gene programs, associated with lung fibrosis. A set of these genes contain a triplex site directly at their promoter and are expressed in fibroblasts. We confirm the formation of RNA:dsDNA formation with target promoters. We find that Fendrr with the Wnt signalling pathway regulates these genes, implicating that Fendrr synergizes with Wnt signalling in lung fibrosis.
The first evaluation of an ultra-high granularity digital electromagnetic calorimeter prototype using 1.0-5.8 GeV/c electrons is presented. The 25×106 pixel detector consists of 24 layers of ALPIDE CMOS MAPS sensors, with a pitch of around 30~μm, and has a depth of almost 20 radiation lengths of tungsten absorber. Ultra-thin cables allow for a very compact design. The properties that are critical for physics studies are measured: electromagnetic shower response, energy resolution and linearity. The stochastic energy resolution is comparable with the state-of-the art resolution for a Si-W calorimeter, with data described well by a simulation model using GEANT and Allpix2. The performance achieved makes this technology a good candidate for use in the ALICE FoCal upgrade, and in general demonstrates the strong potential for future applications in high-energy physics.
The first evaluation of an ultra-high granularity digital electromagnetic calorimeter prototype using 1.0-5.8 GeV/c electrons is presented. The 25×106 pixel detector consists of 24 layers of ALPIDE CMOS MAPS sensors, with a pitch of around 30~μm, and has a depth of almost 20 radiation lengths of tungsten absorber. Ultra-thin cables allow for a very compact design. The properties that are critical for physics studies are measured: electromagnetic shower response, energy resolution and linearity. The stochastic energy resolution is comparable with the state-of-the art resolution for a Si-W calorimeter, with data described well by a simulation model using GEANT and Allpix2. The performance achieved makes this technology a good candidate for use in the ALICE FoCal upgrade, and in general demonstrates the strong potential for future applications in high-energy physics.
The first evaluation of an ultra-high granularity digital electromagnetic calorimeter prototype using 1.0-5.8 GeV/c electrons is presented. The 25×106 pixel detector consists of 24 layers of ALPIDE CMOS MAPS sensors, with a pitch of around 30~μm, and has a depth of almost 20 radiation lengths of tungsten absorber. Ultra-thin cables allow for a very compact design. The properties that are critical for physics studies are measured: electromagnetic shower response, energy resolution and linearity. The stochastic energy resolution is comparable with the state-of-the art resolution for a Si-W calorimeter, with data described well by a simulation model using GEANT and Allpix2. The performance achieved makes this technology a good candidate for use in the ALICE FoCal upgrade, and in general demonstrates the strong potential for future applications in high-energy physics.
The first evaluation of an ultra-high granularity digital electromagnetic calorimeter prototype using 1.0-5.8 GeV/c electrons is presented. The 25×106 pixel detector consists of 24 layers of ALPIDE CMOS MAPS sensors, with a pitch of around 30~μm, and has a depth of almost 20 radiation lengths of tungsten absorber. Ultra-thin cables allow for a very compact design. The properties that are critical for physics studies are measured: electromagnetic shower response, energy resolution and linearity. The stochastic energy resolution is comparable with the state-of-the art resolution for a Si-W calorimeter, with data described well by a simulation model using GEANT and Allpix2. The performance achieved makes this technology a good candidate for use in the ALICE FoCal upgrade, and in general demonstrates the strong potential for future applications in high-energy physics.
We demonstrate ultra-sharp (≲10 nm) lateral p-n junctions in graphene using electronic transport, scanning tunneling microscopy, and first principles calculations. The p-n junction lies at the boundary between differentially-doped regions of a graphene sheet, where one side is intrinsic and the other is charge-doped by proximity to a flake of α-RuCl3 across a thin insulating barrier. We extract the p-n junction contribution to the device resistance to place bounds on the junction width. We achieve an ultra-sharp junction when the boundary between the intrinsic and doped regions is defined by a cleaved crystalline edge of α-RuCl3 located 2 nm from the graphene. Scanning tunneling spectroscopy in heterostructures of graphene, hexagonal boron nitride, and α-RuCl3 shows potential variations on a sub-10 nm length scale. First principles calculations reveal the charge-doping of graphene decays sharply over just nanometers from the edge of the α-RuCl3 flake.
We demonstrate ultra-sharp (≲10 nm) lateral p-n junctions in graphene using electronic transport, scanning tunneling microscopy, and first principles calculations. The p-n junction lies at the boundary between differentially-doped regions of a graphene sheet, where one side is intrinsic and the other is charge-doped by proximity to a flake of α-RuCl3 across a thin insulating barrier. We extract the p-n junction contribution to the device resistance to place bounds on the junction width. We achieve an ultra-sharp junction when the boundary between the intrinsic and doped regions is defined by a cleaved crystalline edge of α-RuCl3 located 2 nm from the graphene. Scanning tunneling spectroscopy in heterostructures of graphene, hexagonal boron nitride, and α-RuCl3 shows potential variations on a sub-10 nm length scale. First principles calculations reveal the charge-doping of graphene decays sharply over just nanometers from the edge of the α-RuCl3 flake.
Intermediate Mass Ratio Inspirals (IMRIs) will be observable with space-based gravitational wave detectors such as the Laser Interferometer Space Antenna (LISA). To this end, the environmental effects in such systems have to be modeled and understood. These effects can include (baryonic) accretion disks and dark matter (DM) overdensities, so called spikes. For the first time, we model an IMRI system with both an accretion disk and a DM spike present and compare their effects on the inspiral and the emitted gravitational wave signal. We study the eccentricity evolution, employ the braking index and derive the dephasing index, which turn out to be complementary observational signatures. They allow us to disentangle the accretion disk and DM spike effects in the IMRI system.
Circularization vs. eccentrification in intermediate mass ratio inspirals inside dark matter spikes
(2022)
Inspirals of an Intermediate Mass Black Hole (IMBH) and a solar mass type object will be observable by space based gravitational wave detectors such as The Laser Interferometer Space Antenna (LISA). A dark matter overdensity around an IMBH - a dark matter spike - can affect the orbital evolution of the system. We consider here such Intermediate Mass Ratio Inspirals on eccentric orbits, experiencing dynamical friction of the dark matter spike. We find that by including the phase space distribution of the dark matter, the dynamical friction tends to circularize the orbit, in contrast to previous inquiries. We derive a general condition for circularization or eccentrification for any given dissipative force. In addition to the dephasing, we suggest using the circularization rate as another probe of the dark matter spike. Observing these effects would be an indicator for the particle nature of dark matter.
Recent findings in permanent cell lines suggested that SARS-CoV-2 Omicron BA.1 induces a stronger interferon response than Delta. Here, we show that BA.1 and BA.5 but not Delta induce an antiviral state in air-liquid interface (ALI) cultures of primary human bronchial epithelial (HBE) cells and primary human monocytes. Both Omicron subvariants caused the production of biologically active type I (α/β) and III (λ) interferons and protected cells from super-infection with influenza A viruses. Notably, abortive Omicron infection of monocytes was sufficient to protect monocytes from influenza A virus infection. Interestingly, while influenza-like illnesses surged during the Delta wave in England, their spread rapidly declined upon the emergence of Omicron. Mechanistically, Omicron-induced interferon signalling was mediated via double-stranded RNA recognition by MDA5, as MDA5 knock-out prevented it. The JAK/ STAT inhibitor baricitinib inhibited the Omicron-mediated antiviral response, suggesting it is caused by MDA5-mediated interferon production, which activates interferon receptors that then trigger JAK/ STAT signalling. In conclusion, our study 1) demonstrates that only Omicron but not Delta induces a substantial interferon response in physiologically relevant models, 2) shows that Omicron infection protects cells from influenza A virus super-infection, and 3) indicates that BA.1 and BA.5 induce comparable antiviral states.
Reliable, easy-to-handle phenotypic screening platforms are needed for the identification of anti-SARS-CoV-2 compounds. Here, we present caspase 3/7 activity as a read-out for monitoring the replication of SARS-CoV-2 isolates from different variants, including a remdesivir-resistant strain, and of other coronaviruses in a broad range of cell culture models, independently of cytopathogenic effect formation. Compared to other cell culture models, the Caco-2 subline Caco-2-F03 displayed superior performance, as it possesses a stable SARS-CoV-2 susceptible phenotype and does not produce false-positive hits due to drug-induced phospholipidosis. A proof-of-concept screen of 1796 kinase inhibitors identified known and novel antiviral drug candidates including inhibitors of PHGDH, CLK-1, and CSF1R. The activity of the PHGDH inhibitor NCT-503 was further increased in combination with the HK2 inhibitor 2-deoxy-D-glucose, which is in clinical development for COVID-19. In conclusion, caspase 3/7 activity detection in SARS-CoV-2-infected Caco-2F03 cells provides a simple phenotypic high-throughput screening platform for SARS-CoV-2 drug candidates that reduces false positive hits.
Recently, we have shown that SARS-CoV-2 Omicron virus isolates are less effective at inhibiting the host cell interferon response than Delta viruses. Here, we present further evidence that reduced interferon-antagonising activity explains at least in part why Omicron variant infections are inherently less severe than infections with other SARS-CoV-2 variants. Most importantly, we here also show that Omicron variant viruses display enhanced sensitivity to interferon treatment, which makes interferons promising therapy candidates for Omicron patients, in particular in combination with other antiviral agents.
Omicron BA.1 variant isolates were previously shown to replicate less effectively in interferon-competent cells and to be more sensitive to interferon treatment than a Delta isolate. Here, an Omicron BA.2 isolate displayed intermediate replication patterns in interferon-competent Caco-2-F03 cells when compared to BA.1 and Delta isolates. Moreover, BA.2 was less sensitive than BA.1 and similarly sensitive as Delta to betaferon treatment. Delta and BA.1 displayed similar sensitivity to the approved anti-SARS-CoV-2 drugs remdesivir, nirmatrelvir, EIDD-1931 (the active metabolite of molnupiravir) and the protease inhibitor aprotinin, whereas BA.2 was less sensitive than Delta and BA.1 to EIDD-1931, nirmatrelvir and aprotinin. Nirmatrelvir, EIDD-1931, and aprotinin (but not remdesivir) exerted synergistic antiviral activity in combination with betaferon, with some differences in the extent of synergism detected between the different SARS-CoV-2 variants. In conclusion, even closely related SARS-CoV-2 (sub)variants can differ in their biology and in their response to antiviral treatments. Betaferon combinations with nirmatrelvir and, in particular, with EIDD-1931 and aprotinin displayed high levels of synergism, which makes them strong candidates for clinical testing. Notably, effective antiviral combination therapies are desirable, as a higher efficacy is expected to reduce resistance formation.
The SARS-CoV-2 Omicron variant is currently causing a large number of infections in many countries. A number of antiviral agents are approved or in clinical testing for the treatment of COVID-19. Despite the high number of mutations in the Omicron variant, we here show that Omicron isolates display similar sensitivity to eight of the most important anti-SARS-CoV-2 drugs and drug candidates (including remdesivir, molnupiravir, and PF-07321332, the active compound in paxlovid), which is of timely relevance for the treatment of the increasing number of Omicron patients. Most importantly, we also found that the Omicron variant displays a reduced capability of antagonising the host cell interferon response. This provides a potential mechanistic explanation for the clinically observed reduced pathogenicity of Omicron variant viruses compared to Delta variant viruses.
The antiviral drugs tecovirimat, brincidofovir, and cidofovir are considered for mpox (monkeypox) treatment despite a lack of clinical evidence. Moreover, their use is affected by toxic side-effects (brincidofovir, cidofovir), limited availability (tecovirimat), and potentially by resistance formation. Hence, additional, readily available drugs are needed. Here, therapeutic concentrations of nitroxoline, a hydroxyquinoline antibiotic with a favourable safety profile in humans, inhibited the replication of 12 mpox virus isolates from the current outbreak in primary cultures of human keratinocytes and fibroblasts and a skin explant model by interference with host cell signalling. Tecovirimat, but not nitroxoline, treatment resulted in rapid resistance development. Nitroxoline remained effective against the tecovirimat-resistant strain and increased the anti-mpox virus activity of tecovirimat and brincidofovir. Moreover, nitroxoline inhibited bacterial and viral pathogens that are often co-transmitted with mpox. In conclusion, nitroxoline is a repurposing candidate for the treatment of mpox due to both antiviral and antimicrobial activity.