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We report on the measurement of the inclusive Υ (1S) production in Pb–Pb collisions at √sNN = 2.76 TeV carried out at forward rapidity (2.5 < y < 4) and down to zero transverse momentum using its μ+μ−decay channel with the ALICE detector at the Large Hadron Collider. A strong suppression of the inclusive Υ (1S) yield is observed with respect to pp collisions scaled by the number of independent nucleon–nucleon collisions. The nuclear modification factor, for events in the 0–90% centrality range, amounts to 0.30 ± 0.05(stat) ± 0.04(syst). The observed Υ (1S) suppression tends to increase with the centrality of the collision and seems more pronounced than in corresponding mid-rapidity measurements. Our results are compared with model calculations, which are found to underestimate the measured suppression and fail to reproduce its rapidity dependence.
Transverse momentum spectra of π±, K± and p(p¯) up to pT = 20 GeV/c at mid-rapidity in pp and Pb-Pb collisions at sNN−−−√= 2.76 TeV have been measured using the ALICE detector at the Large Hadron Collider. The proton-to-pion and the kaon-to-pion ratios both show a distinct peak at pT≈3GeV/c in central Pb-Pb collisions. Below the peak, pT < 3 GeV/c, both ratios are in good agreement with hydrodynamical calculations, suggesting that the peak itself is dominantly the result of radial flow rather than anomalous hadronization processes. For pT > 10 GeV/c particle ratios in pp and Pb-Pb collisions are in agreement and the nuclear modification factors for π±, K± and p(p¯) indicate that, within the systematic and statistical uncertainties, the suppression is the same. This suggests that the chemical composition of leading particles from jets in the medium is similar to that of vacuum jets.
The pT-differential production cross section of electrons from semileptonic decays of heavy-flavor hadrons has been measured at mid-rapidity in proton-proton collisions at s√=2.76 TeV in the transverse momentum range 0.5 < pT < 12 GeV/c with the ALICE detector at the LHC. The analysis was performed using minimum bias events and events triggered by the electromagnetic calorimeter. Predictions from perturbative QCD calculations agree with the data within the theoretical and experimental uncertainties.
The pT-differential production cross section of electrons from semileptonic decays of heavy-flavor hadrons has been measured at mid-rapidity in proton-proton collisions at s√=2.76 TeV in the transverse momentum range 0.5 < pT < 12 GeV/c with the ALICE detector at the LHC. The analysis was performed using minimum bias events and events triggered by the electromagnetic calorimeter. Predictions from perturbative QCD calculations agree with the data within the theoretical and experimental uncertainties.
Hintergrund: Ab Frühjahr 2020 kam es zur weltweiten Verbreitung von SARS-CoV‑2 mit der heute als erste Welle der Pandemie bezeichneten Phase ab März 2020. Diese resultierte an vielen Kliniken in Umstrukturierungen und Ressourcenverschiebungen. Ziel unserer Arbeit war die Erfassung der Auswirkungen der Pandemie auf die universitäre Hals-Nasen-Ohren(HNO)-Heilkunde für die Forschung, Lehre und Weiterbildung. Material und Methoden: Die Direktorinnen und Direktoren der 39 Universitäts-HNO-Kliniken in Deutschland wurden mithilfe einer strukturierten Online-Befragung zu den Auswirkungen der Pandemie im Zeitraum von März bis April 2020 auf die Forschung, Lehre und die Weiterbildung befragt. Ergebnisse: Alle 39 Direktorinnen und Direktoren beteiligten sich an der Umfrage. Hiervon gaben 74,4 % (29/39) an, dass es zu einer Verschlechterung ihrer Forschungstätigkeit infolge der Pandemie gekommen sei. Von 61,5 % (24/39) wurde berichtet, dass pandemiebezogene Forschungsaspekte aufgegriffen wurden. Von allen Kliniken wurde eine Einschränkung der Präsenzlehre berichtet und 97,5 % (38/39) führten neue digitale Lehrformate ein. Im Beobachtungszeitraum sahen 74,4 % der Klinikdirektoren die Weiterbildung der Assistenten nicht gefährdet. Schlussfolgerung: Die Ergebnisse geben einen Einblick in die heterogenen Auswirkungen der Pandemie. Die kurzfristige Bearbeitung pandemiebezogener Forschungsthemen und die Einführung innovativer digitaler Konzepte für die studentische Lehre belegt eindrücklich das große innovative Potenzial und die schnelle Reaktionsfähigkeit der HNO-Universitätskliniken, um auch während der Pandemie ihre Aufgaben in der Forschung, Lehre und Weiterbildung bestmöglich zu erfüllen.
Background: Spondylodiscitis is a potentially life-threatening infection of the intervertebral disk and adjacent vertebral bodies, with a mortality rate of 2–20%. Given the aging population, the increase in immunosuppression, and intravenous drug use in England, the incidence of spondylodiscitis is postulated to be increasing; however, the exact epidemiological trend in England remains unknown.
Objective: The Hospital Episode Statistics (HES) database contains details of all secondary care admissions across NHS hospitals in England. This study aimed to use HES data to characterise the annual activity and longitudinal change of spondylodiscitis in England.
Methods: The HES database was interrogated for all cases of spondylodiscitis between 2012 and 2019. Data for the length of stay, waiting time, age-stratified admissions, and ‘Finished Consultant Episodes’ (FCEs), which correspond to a patient's hospital care under a lead clinician, were analysed.
Results: In total, 43135 FCEs for spondylodiscitis were identified between 2012 and 2022, of which 97.1% were adults. Overall admissions for spondylodiscitis have risen from 3 per 100,000 population in 2012/13 to 4.4 per 100,000 population in 2020/21. Similarly, FCEs have increased from 5.8 to 10.3 per 100,000 population, in 2012–2013 and 2020/21 respectively. The highest increase in admissions from 2012 to 2021 was recorded for those aged 70–74 (117% increase) and aged 75-59 (133% increase), among those of working age for those aged 60–64 years (91% increase).
Conclusion: Population-adjusted admissions for spondylodiscitis in England have risen by 44% between 2012 and 2021. Healthcare policymakers and providers must acknowledge the increasing burden of spondylodiscitis and make spondylodiscitis a research priority.
Oral e-Poster Presentations - Booth 2: Spine 1 (Trauma&Misc), September 25, 2023, 10:00 AM - 10:40 AM
Background: Spondylodiscitis is a prevalent type of spinal infection, with pyogenic spondylodiscitis being the most common subtype. While antibiotic therapy is the standard treatment, some argue that early surgery can aid in infection clearance, improve survival rates, and prevent long-term complications such as deformities. However, others view early surgery as excessively risky. Due to the high mortality rate of up to 20%, it is crucial to determine the most effective treatment.
Methods: The primary objective of this study was to compare the mortality rate, relapse rate, and length of hospital stay for conservative and early surgical treatments of pyogenic spondylodiscitis, including determinants of outcomes. The study was registered on PROSPERO with the registration number CRD42022312573. The databases MEDLINE, Embase, Scopus, PubMed, and JSTOR were searched for original studies comparing conservative and early surgical treatments of pyogenic spondylodiscitis. The included studies were assessed using the ROBINS-1 tool, and eligible studies were evaluated using meta-analyses, influence, and regression analyses.
Results: The systematic review included 31 studies. The meta-analysis, which had a pooled sample size of 10,954 patients from 21 studies, found that the pooled mortality rate among patients treated with early surgery was 8%, while the rate was 13% for patients treated conservatively. The mean proportion of relapse/failure was 15% for patients treated with early surgery and 21% for those treated conservatively. Furthermore, the analysis concluded that early surgical treatment is associated with a 40% and 39% risk reduction in relapse/failure and mortality rates, respectively, when compared to conservative management. Additionally, early surgical treatment resulted in a 7.75-day reduction in length of hospital stay per patient (p<0.01). The most highly significant predictors of treatment outcome were found to be intravenous drug use, diabetes, the presence of an epidural abscess, positive cultures, location of infection, and age (p<0.001).
Conclusions: Overall, early surgical management was found to be consistently significantly more effective than conservative management in terms of relapse/failure and mortality rates when treating pyogenic spondylodiscitis, particularly for non-spinal epidural abscess spondylodiscitis.
Introduction: Spondylodiscitis is the commonest form of infectious disease of the spine and harbours a high mortality rate of up to 20%. Recent demographic trends in Germany, such as an aging population, immunosuppression, and intravenous drug use, suggest that the incidence of spondylodiscitis may be on the rise. However, the exact epidemiological development of the disease remains uncertain. This study aims to analyse the burden on the tertiary healthcare system in Germany using data from the Federal Statistical Office of Germany (FSOG) database.
Materials and Methods: All cases of spondylodiscitis diagnosed between 2005 and 2021 were identified from the FSOG database. The study characterised the mean duration of hospital stays, total and population-adjusted number of diagnoses made, age-stratified incidence, and outcomes of hospitalised patients.
Results: A total of 131,982 diagnoses for spondylodiscitis were identified between 2005 and 2021. The number of diagnoses for spondylodiscitis has doubled during this period, from 5.4/100,000 population in 2005 to 11/100,000 population in 2021. The highest increase in admissions was recorded for those aged 90 years and above (+1307%), 80-89 (+376%) and 70-79 (+99%). Hospital discharges to rehabilitation facilities have increased by 160%, and discharges against medical advice by 91%. On the other hand, during the analysed period, the in-hospital mortality rate has decreased by 52%.
Conclusion: The population-adjusted incidence of spondylodiscitis in Germany has more than doubled between 2005 and 2021, highlighting the clinical relevance of this disease. During the same period, in-hospital mortality dropped by half. These findings suggest the need for further investigation into optimal therapy, particularly the role and timing of surgical treatment.
Long-range angular correlations on the near and away side in p–Pb collisions at √sNN=5.02 TeV
(2013)
Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p–Pb collisions at a nucleon–nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5<pT,assoc<pT,trig<4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and pT bins, and the widths show no significant evolution with event multiplicity or pT. These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge.
Introduction: The optimal treatment of patients with spinal infections remains a controversial topic. Within Europe, fundamentally different therapeutic concepts are found. Therefore, the aim of this study was to compare the outcome of patients who received surgical vs. antibiotic treatment alone for primary pyogenic spondylodiscitis in an international cohort analysis.
Materials and Methods: The retrospectively compiled databases of tertiary high-volume spine centers served as the baseline for this study. All documented cases of primary spondylodiscitis treated surgically and conservatively in the period of 2017-2022 were included and grouped according to the therapeutic concept: conservative vs. surgical treatment. Independent investigators collected the relevant clinical and radiological data. The primary endpoint of this study was mortality rate; secondary endpoints were relapse rate and persisting neurological deficit.
Results: A total of 392 patients were included in the analysis (155 females with a mean age of 68 years). Of these, 95 cases were treated conservatively (CoT) and 297 cases were treated surgically (SuT). There was no significant difference (p<0.01) related to patient’s disease characteristics: Lumbar was the main location (n=240, CoT 58/ SuT 182, p=0.97) followed by thoracic (n=70, CoT 24/ SuT 46, p=0,03) and cervical (n=47, CoT 7/ SuT 40, p=0.11) region. A multilocular spinal infection was present in 32 patients (CoT 3/ SuT 29, p=0.04). 181 cases (CoT 36/ SuT 145, p=0.06) presented with an epidural abscess. Neurological deficits were recorded in 100 cases (CoT 26/ SuT 74, p=0.63), and septic conditions in 88 cases (CoT 26/ SuT 62, p=0.19). Pre-existing conditions like Diabetes (p=0.57), renal failure (p= 0.97), hepatopathy (p= 0.15), malignoma (p=0.39) or i.v. drug abuse (p=0.93) did also not differ between the groups. The mortality rate of all conservatively treated was 24.2% (23 cases) and 6.7% (20 cases) in all surgically treated patients (p<0.001). A follow-up of ≥ 6 weeks was available in 289 cases (CoT 83, SuT 206 ). In this subset of patients relapse of infection occurred in six (7.2%) and 23 (11.2%) cases in the conservative and early surgical treatment group, respectively (p=0.69). Persisting neurological deficit was recorded in 21 (25.3%) of conservatively treated and 51 (24.8%) of surgically treated cases (p=0.92).
Conclusion: Whereas relapse rates and persisting neurological deficit were not found to differ significantly, the results of this international data analyses, with their respective limitations, clearly support the growing evidence of a significantly reduced mortality rate after surgical therapy for primary pyogenic spondylodiscitis when compared to conservative treatment regimen.
Spinal Tumors / Infections (Spine Parallel Session v.3), September 27, 2023, 8:30 AM - 10:00 AM
Background: The optimal treatment of patients with spinal infections remains a controversial topic. While there is some consensus regarding the indication for surgical intervention in infections with neurologic deficit, significant deformity or progressive disease, other situations remain controversial. Within Europe, fundamentally different therapeutic concepts are found. Therefore, the aim of this study was to compare the outcome of patients who received surgical vs. antibiotic treatment alone for primary pyogenic spondylodiscitis in an international cohort analysis.
Methods: The retrospectively compiled databases of tertiary high-volume spine centers served as the baseline for this study. All documented cases of primary spondylodiscitis treated surgically and conservatively in the period of 2017-2022 were included and grouped according to the therapeutic concept: conservative vs. surgical treatment. Independent investigators collected the relevant clinical and radiological data. The primary endpoint of this study was mortality rate; secondary endpoints were relapse rate and persisting neurological deficit.
Results: A total of 392 patients were included in the analysis (155 females and 237 males with a mean age of 68 years). Of these, 95 cases were treated conservatively (CoT) and 297 cases were treated surgically (SuT). Most of conservatively treated patients were treated in the United Kingdom (CoT 81/ SuT 7), while most of the surgically treated cases were treated in Germany (CoT 14/ SuT 290). There was no significant difference (p<0.01) related to patient’s disease characteristics:
Lumbar was the main location (n=240, CoT 58/ SuT 182, p=0.97) followed by thoracic (n=70, CoT 24/ SuT 46, p=0,03) and cervical (n=47, CoT 7/ SuT 40, p=0.11) region. A multilocular spinal infection was present in 32 patients (CoT 3/ SuT 29, p=0.04). 181 cases (CoT 36/ SuT 145, p=0.06) presented with an epidural abscess. Neurological deficits were recorded in 100 cases (CoT 26/ SuT 74, p=0.63), and septic conditions in 88 cases (CoT 26/ SuT 62, p=0.19). Pre-existing conditions like Diabetes (CoT 20/, SuT 71, p=0.57), renal failure (CoT 19/ SuT 60, p= 0.97), hepatopathy (CoT 4/ SuT 26, p= 0.15), malignoma (CoT 9/ SuT 38, p=0.39) or i.v. drug abuse (CoT 5/, SuT 15, p=0.93) did also not differ between the groups.
The mortality rate of all conservatively treated was 24.2% (23 cases) and 6.7% (20 cases) in all surgically treated patients (p<0.001). A follow-up of ≥ 6 weeks was available in 289 cases (CoT 83, SuT 206 ). In this subset of patients relapse of infection occurred in six (7.2%) and 23 (11.2%) cases in the conservative and early surgical treatment group, respectively (p=0.69). Persisting neurological deficit was recorded in 21 (25.3%) of conservatively treated and 51 (24.8%) of surgically treated cases (p=0.92).
Conclusions: Whereas relapse rates and persisting neurological deficit were not found to differ significantly, the results of this international data analyses, with their respective limitations, clearly support the growing evidence of a significantly reduced mortality rate after surgical therapy for primary pyogenic spondylodiscitis when compared to conservative treatment regimen.
Multi-subunit ATPase-dependent chromatin remodelling complexes SWI/SNF (switch/sucrose non-fermentable) are fundamental epigenetic regulators of gene transcription. Functional genomic studies revealed a remarkable mutation prevalence of SWI/SNF-encoding genes in 20–25% of all human cancers, frequently driving oncogenic programmes. Some SWI/SNF-mutant cancers are hypersensitive to perturbations in other SWI/SNF subunits, regulatory proteins and distinct biological pathways, often resulting in sustained anticancer effects and synthetic lethal interactions. Exploiting these vulnerabilities is a promising therapeutic strategy. Here, we review the importance of SWI/SNF chromatin remodellers in gene regulation as well as mechanisms leading to assembly defects and their role in cancer development. We will focus in particular on emerging strategies for the targeted therapy of SWI/SNF-deficient cancers using chemical probes, including proteolysis targeting chimeras, to induce synthetic lethality.
The transport of air masses originating from the Asian monsoon anticyclone into the extratropical upper troposphere and lower stratosphere (Ex-UTLS) above potential temperatures Θ = 380K was identified during the HALO aircraft mission TACTS in August and September 2012. In-situ measurements of CO, O3 and N2O during TACTS Flight 2 on the 30 August 2012 show the irreversible mixing of aged with younger (originating from the troposphere) stratospheric air masses within the Ex-UTLS. Backward trajectories calculated with the trajetory module of the CLaMS model indicate that these tropospherically affected air masses originate from the Asian monsoon anticyclone. From the monsoon circulation region these air masses are quasi-isentropically transported above Θ = 380 K into the Ex-UTLS where they subsequently mix with stratospheric air masses. The overall trace gas distribution measured during TACTS shows that this transport pathway has a significant impact on the Ex-UTLS during boreal summer and autumn. This leads to an intensification of the tropospheric influence on the Ex-UTLS with ∆Θ > 30 K (relative to the tropopause) within three weeks during the TACTS mission. In the same time period a weakening of the tropospheric influence on the lowermost stratosphere (LMS) is determined. Therefore, the study shows that the transport of air masses originating from the Asian summer monsoon region within the lower stratosphere above Θ = 380K is of major importance for the change of the chemical composition of the Ex-UTLS from summer to autumn.
The transport of air masses originating from the Asian monsoon anticyclone into the extratropical upper troposphere and lower stratosphere (Ex-UTLS) above potential temperatures Θ = 380 K was identified during the HALO aircraft mission TACTS in August and September 2012. In situ measurements of CO, O3 and N2O during TACTS flight 2 on 30 August 2012 show the irreversible mixing of aged stratospheric air masses with younger (recently transported from the troposphere) ones within the Ex-UTLS. Backward trajectories calculated with the trajectory module of CLaMS indicate that these tropospherically affected air masses originate from the Asian monsoon anticyclone. These air masses are subsequently transported above potential temperatures Θ = 380 K from the monsoon circulation region into the Ex-UTLS, where they subsequently mix with stratospheric air masses. The overall trace gas distribution measured during TACTS shows that this transport pathway had affected the chemical composition of the Ex-UTLS during boreal summer and autumn 2012. This leads to an intensification of the tropospheric influence on the extratropical lower stratosphere with PV > 8 pvu within 3 weeks during the TACTS mission. During the same time period a weakening of the tropospheric influence on the lowermost stratosphere (LMS) is determined. The study shows that the transport of air masses originating from the Asian summer monsoon region within the lower stratosphere affects the change in the chemical composition of the Ex-UTLS over Europe and thus contributes to the flushing of the LMS during summer 2012.
The pT-differential inclusive production cross section of the prompt charm-strange meson Ds+ in the rapidity range |y|<0.5 was measured in proton–proton collisions at s=7 TeV at the LHC using the ALICE detector. The analysis was performed on a data sample of 2.98×108 events collected with a minimum-bias trigger. The corresponding integrated luminosity is Lint=4.8 nb−1. Reconstructing the decay Ds+→ϕπ+, with ϕ→K−K+, and its charge conjugate, about 480 Ds± mesons were counted, after selection cuts, in the transverse momentum range 2<pT<12 GeV/c. The results are compared with predictions from models based on perturbative QCD. The ratios of the cross sections of four D meson species (namely D0, D+, D⁎+ and Ds+) were determined both as a function of pT and integrated over pT after extrapolating to full pT range, together with the strangeness suppression factor in charm fragmentation. The obtained values are found to be compatible within uncertainties with those measured by other experiments in e+e−, ep and pp interactions at various centre-of-mass energies.
Identical neutral kaon pair correlations are measured in √s=7 TeV pp collisions in the ALICE experiment. One-dimensional Ks0Ks0 correlation functions in terms of the invariant momentum difference of kaon pairs are formed in two multiplicity and two transverse momentum ranges. The femtoscopic parameters for the radius and correlation strength of the kaon source are extracted. The fit includes quantum statistics and final-state interactions of the a0/f0 resonance. Ks0Ks0 correlations show an increase in radius for increasing multiplicity and a slight decrease in radius for increasing transverse mass, mT, as seen in ππ correlations in pp collisions and in heavy-ion collisions. Transverse mass scaling is observed between the Ks0Ks0 and ππ radii. Also, the first observation is made of the decay of the f2′(1525) meson into the Ks0Ks0 channel in pp collisions.
The elliptic, v2, triangular, v3, and quadrangular, v4, azimuthal anisotropic flow coefficients are measured for unidentified charged particles, pions, and (anti-)protons in Pb–Pb collisions at √sNN=2.76 TeV with the ALICE detector at the Large Hadron Collider. Results obtained with the event plane and four-particle cumulant methods are reported for the pseudo-rapidity range |η|<0.8 at different collision centralities and as a function of transverse momentum, pT, out to pT=20 GeV/c. The observed non-zero elliptic and triangular flow depends only weakly on transverse momentum for pT>8 GeV/c. The small pT dependence of the difference between elliptic flow results obtained from the event plane and four-particle cumulant methods suggests a common origin of flow fluctuations up to pT=8 GeV/c. The magnitude of the (anti-)proton elliptic and triangular flow is larger than that of pions out to at least pT=8 GeV/c indicating that the particle type dependence persists out to high pT.
The production cross section of electrons from semileptonic decays of beauty hadrons was measured at mid-rapidity (|y|<0.8) in the transverse momentum range 1<pT<8 GeV/c with the ALICE experiment at the CERN LHC in pp collisions at a center of mass energy √s=7 TeV using an integrated luminosity of 2.2 nb−1. Electrons from beauty hadron decays were selected based on the displacement of the decay vertex from the collision vertex. A perturbative QCD calculation agrees with the measurement within uncertainties. The data were extrapolated to the full phase space to determine the total cross section for the production of beauty quark–antiquark pairs.
The inclusive transverse momentum (pT) distributions of primary charged particles are measured in the pseudo-rapidity range |η|<0.8 as a function of event centrality in Pb–Pb collisions at √sNN=2.76 TeV with ALICE at the LHC. The data are presented in the pT range 0.15<pT<50 GeV/c for nine centrality intervals from 70–80% to 0–5%. The results in Pb–Pb are presented in terms of the nuclear modification factor RAA using a pp reference spectrum measured at the same collision energy. We observe that the suppression of high-pT particles strongly depends on event centrality. The yield is most suppressed in central collisions (0–5%) with RAA≈0.13 at pT=6–7 GeV/c. Above pT=7 GeV/c, there is a significant rise in the nuclear modification factor, which reaches RAA≈0.4 for pT>30 GeV/c. In peripheral collisions (70–80%), only moderate suppression (RAA=0.6–0.7) and a weak pT dependence is observed. The measured nuclear modification factors are compared to other measurements and model calculations.
The ALICE Collaboration has made the first measurement at the LHC of J/ψ photoproduction in ultra-peripheral Pb–Pb collisions at sNN=2.76 TeV. The J/ψ is identified via its dimuon decay in the forward rapidity region with the muon spectrometer for events where the hadronic activity is required to be minimal. The analysis is based on an event sample corresponding to an integrated luminosity of about 55 μb−1. The cross section for coherent J/ψ production in the rapidity interval −3.6<y<−2.6 is measured to be dσJ/ψcoh/dy=1.00±0.18(stat)−0.26+0.24(syst) mb. The result is compared to theoretical models for coherent J/ψ production and found to be in good agreement with those models which include nuclear gluon shadowing.
Challenges of FAIR phase 0
(2018)
After two-year's shutdown, the GSI accelerators plus the latest addition of storage ring CRYRING, will be back into operation in 2018 as the FAIR phase 0 with the goal to fulfill the needs of scientific community and the FAIR accelerators and detector development. Even though GSI has been well known for its operation of a variety of ion beams ranging from proton up to uranium for multi research areas such as nuclear physics, astrophysics, biophysics, material science, the upcoming beam time faces a number of challenges in re-commissioning its existing circular accelerators with brand new control system and upgrade of beam instrumentations, as well as in rising failures of dated components and systems. The cycling synchrotron SIS18 has been undergoing a set of upgrade measures for fulfilling future FAIR operation, among which many measures will also be commissioned during the upcoming beam time. This paper presents the highlights of the challenges such as re-establishing the high intensity heavy ion operation as well as parallel operation mode for serving multi users. The status of preparation including commissioning results will also be reported.
The balance function is a new observable based on the principle that charge is locally conserved when particles are pair produced. Balance functions have been measured for charged particle pairs and identified charged pion pairs in Au+Au collisions at sqrt[sNN]=130 GeV at the Relativistic Heavy Ion Collider using STAR. Balance functions for peripheral collisions have widths consistent with model predictions based on a superposition of nucleon-nucleon scattering. Widths in central collisions are smaller, consistent with trends predicted by models incorporating late hadronization.
Azimuthal anisotropy (v2) and two-particle angular correlations of high pT charged hadrons have been measured in Au+Au collisions at sqrt[sNN]=130 GeV for transverse momenta up to 6 GeV/c, where hard processes are expected to contribute significantly. The two-particle angular correlations exhibit elliptic flow and a structure suggestive of fragmentation of high pT partons. The monotonic rise of v2(pT) for pT<2 GeV/c is consistent with collective hydrodynamical flow calculations. At pT>3 GeV/c, a saturation of v2 is observed which persists up to pT=6 GeV/c.
Azimuthal anisotropy (v2) and two-particle angular correlations of high pT charged hadrons have been measured in Au+Au collisions at sqrt[sNN]=130 GeV for transverse momenta up to 6 GeV/c, where hard processes are expected to contribute significantly. The two-particle angular correlations exhibit elliptic flow and a structure suggestive of fragmentation of high pT partons. The monotonic rise of v2(pT) for pT<2 GeV/c is consistent with collective hydrodynamical flow calculations. At pT>3 GeV/c, a saturation of v2 is observed which persists up to pT=6 GeV/c.
Elliptic flow holds much promise for studying the early-time thermalization attained in ultrarelativistic nuclear collisions. Flow measurements also provide a means of distinguishing between hydrodynamic models and calculations which approach the low density (dilute gas) limit. Among the effects that can complicate the interpretation of elliptic flow measurements are azimuthal correlations that are unrelated to the reaction plane (nonflow correlations). Using data for Au + Au collisions at sqrt[sNN]=130 GeV from the STAR time projection chamber, it is found that four-particle correlation analyses can reliably separate flow and nonflow correlation signals. The latter account for on average about 15% of the observed second-harmonic azimuthal correlation, with the largest relative contribution for the most peripheral and the most central collisions. The results are also corrected for the effect of flow variations within centrality bins. This effect is negligible for all but the most central bin, where the correction to the elliptic flow is about a factor of 2. A simple new method for two-particle flow analysis based on scalar products is described. An analysis based on the distribution of the magnitude of the flow vector is also described.
We report the first observation of K*(892)0--> pi K in relativistic heavy ion collisions. The transverse momentum spectrum of (K*0+K*0)/2 from central Au+Au collisions at sqrt[sNN]=130 GeV is presented. The ratios of the K*0 yield derived from these data to the yields of negative hadrons, charged kaons, and phi mesons have been measured in central and minimum bias collisions and compared with model predictions and comparable e+e-, pp, and p-barp results. The data indicate no dramatic reduction of K*0 production in relativistic heavy ion collisions despite expected losses due to rescattering effects.
The STAR Collaboration reports the first observation of exclusive rho 0 photoproduction, AuAu-->AuAu rho 0, and rho 0 production accompanied by mutual nuclear Coulomb excitation, AuAu-->Au [star] Au [star] rho 0, in ultraperipheral heavy-ion collisions. The rho 0 have low transverse momenta, consistent with coherent coupling to both nuclei. The cross sections at sqrt[sNN]=130 GeV agree with theoretical predictions treating rho 0 production and Coulomb excitation as independent processes.
We report STAR results on the azimuthal anisotropy parameter v2 for strange particles K0S, Lambda , and Lambda -bar at midrapidity in Au+Au collisions at sqrt[sNN]=130 GeV at the Relativistic Heavy Ion Collider. The value of v2 as a function of transverse momentum, pt, of the produced particle and collision centrality is presented for both particles up to pt~3.0 GeV/c. A strong pt dependence in v2 is observed up to 2.0 GeV/c. The v2 measurement is compared with hydrodynamic model calculations. The physics implications of the pt integrated v2 magnitude as a function of particle mass are also discussed.
Inclusive transverse momentum distributions of charged hadrons within 0.2<pT<6.0 GeV/c have been measured over a broad range of centrality for Au+Au collisions at sqrt[sNN]=130 GeV. Hadron yields are suppressed at high pT in central collisions relative to peripheral collisions and to a nucleon-nucleon reference scaled for collision geometry. Peripheral collisions are not suppressed relative to the nucleon-nucleon reference. The suppression varies continuously at intermediate centralities. The results indicate significant nuclear medium effects on high-pT hadron production in heavy-ion collisions at high energy.
We report the first measurement of strange ( Lambda ) and antistrange ( Lambda -bar) baryon production from sqrt[sNN]=130 GeV Au+Au collisions at the Relativistic Heavy Ion Collider (RHIC). Rapidity density and transverse mass distributions at midrapidity are presented as a function of centrality. The yield of Lambda and Lambda -bar hyperons is found to be approximately proportional to the number of negative hadrons. The production of Lambda -bar hyperons relative to negative hadrons increases very rapidly with transverse momentum. The magnitude of the increase cannot be described by existing hadronic string fragmentation models alone.
Two-pion correlation functions in Au+Au collisions at sqrt[sNN] = 130 GeV have been measured by the STAR (solenoidal tracker at RHIC) detector. The source size extracted by fitting the correlations grows with event multiplicity and decreases with transverse momentum. Anomalously large sizes or emission durations, which have been suggested as signals of quark-gluon plasma formation and rehadronization, are not observed. The Hanbury Brown-Twiss parameters display a weak energy dependence over a broad range in sqrt[sNN].
The first measurements of light antinucleus production in Au+Au collisions at the Relativistic Heavy-Ion Collider are reported. The observed production rates for d-bar and 3He-bar are much larger than in lower energy nucleus-nucleus collisions. A coalescence model analysis of the yields indicates that there is little or no increase in the antinucleon freeze-out volume compared to collisions at CERN SPS energy. These analyses also indicate that the 3He-bar freeze-out volume is smaller than the d-bar freeze-out volume.
We present the first measurement of midrapidity vector meson phi production in Au+Au collisions at RHIC (sqrt[sNN]=130 GeV) from the STAR detector. For the 11% highest multiplicity collisions, the slope parameter from an exponential fit to the transverse mass distribution is T=379±50(stat)±45(syst) MeV, the yield dN/dy=5.73±0.37(stat)±0.69(syst) per event, and the ratio N phi /Nh- is found to be 0.021±0.001(stat)±0.004(syst). The measured ratio N phi /Nh- and T for the phi meson at midrapidity do not change for the selected multiplicity bins.
Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at sqrt[sNN] = 130 GeV using the STAR Time Projection Chamber at the Relativistic Heavy Ion Collider. The elliptic flow signal, v2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.
Bromodomains (BRDs) are conserved protein interaction modules which recognize (read) acetyl-lysine modifications, however their role(s) in regulating cellular states and their potential as targets for the development of targeted treatment strategies is poorly understood. Here we present a set of 25 chemical probes, selective small molecule inhibitors, covering 29 human bromodomain targets. We comprehensively evaluate the selectivity of this probe-set using BROMOscan and demonstrate the utility of the set identifying roles of BRDs in cellular processes and potential translational applications. For instance, we discovered crosstalk between histone acetylation and the glycolytic pathway resulting in a vulnerability of breast cancer cell lines under conditions of glucose deprivation or GLUT1 inhibition to inhibition of BRPF2/3 BRDs. This chemical probe-set will serve as a resource for future applications in the discovery of new physiological roles of bromodomain proteins in normal and disease states, and as a toolset for bromodomain target validation.
We report first results on elliptic flow of identified particles at midrapidity in Au+Au collisions at sqrt[sNN] = 130 GeV using the STAR TPC at RHIC. The elliptic flow as a function of transverse momentum and centrality differs significantly for particles of different masses. This dependence can be accounted for in hydrodynamic models, indicating that the system created shows a behavior consistent with collective hydrodynamical flow. The fit to the data with a simple model gives information on the temperature and flow velocities at freeze-out.
The minimum-bias multiplicity distribution and the transverse momentum and pseudorapidity distributions for central collisions have been measured for negative hadrons ( h-) in Au+Au interactions at sqrt[sNN] = 130 GeV. The multiplicity density at midrapidity for the 5% most central interactions is dNh-/d eta | eta = 0 = 280±1(stat)±20(syst), an increase per participant of 38% relative to pp-bar collisions at the same energy. The mean transverse momentum is 0.508±0.012 GeV/c and is larger than in central Pb+Pb collisions at lower energies. The scaling of the h- yield per participant is a strong function of pperp. The pseudorapidity distribution is almost constant within | eta |<1.
We report the first measurement of inclusive antiproton production at midrapidity in Au+Au collisions at sqrt[sNN] = 130 GeV by the STAR experiment at RHIC. The antiproton transverse mass distributions in the measured transverse momentum range of 0.25<pperp<0.95 GeV/c are found to fall less steeply for more central collisions. The extrapolated antiproton rapidity density is found to scale approximately with the negative hadron multiplicity density.
We report results on the ratio of midrapidity antiproton-to-proton yields in Au+Au collisions at sqrt[sNN] = 130 GeV per nucleon pair as measured by the STAR experiment at RHIC. Within the rapidity and transverse momentum range of | y|<0.5 and 0.4<pt<1.0 GeV/c, the ratio is essentially independent of either transverse momentum or rapidity, with an average of 0.65±0.01(stat)±0.07(syst) for minimum bias collisions. Within errors, no strong centrality dependence is observed. The results indicate that at this RHIC energy, although the p-p-bar pair production becomes important at midrapidity, a significant excess of baryons over antibaryons is still present.
Hintergrund und Fragestellung: Die Severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2)-Pandemie hat die Ausbildung von Medizinstudierenden grundlegend verändert. Die Notwendigkeit von Kontaktbeschränkungen und die damit einhergehende Forderung nach Distanzunterricht hat dazu geführt, dass innerhalb kurzer Zeit digitale Lehrformate umgesetzt werden mussten. Ziel dieser Arbeit war die Auswertung der studentischen Evaluationsergebnisse für virtuellen Unterricht im Fach Hals-Nasen-Ohren-Heilkunde während der SARS-CoV-2-Pandemie und ein Vergleich mit den zuvor erhobenen Evaluationsergebnissen unter Präsenzbedingungen.
Material und Methoden: Untersucht wurden die Evaluationsergebnisse für die Blockpraktika im Wintersemester 2020/21 und im Sommersemester 2021, die in einem virtuellen Format mit kurzer Präsenzphase durchgeführt wurden, sowie die der komplett im konventionellen Präsenzformat durchgeführten Praktika von Sommersemester 2018 bis Wintersemester 2019/20. Die anonyme Befragung der Studierenden bezog sich auf verschiedene Aspekte der Lehrveranstaltung, wie z. B. Organisation, Didaktik und Lernatmosphäre.
Ergebnisse: Von 16 abgefragten Kategorien zeigten 14 (87,5%) signifikant bessere Evaluationsergebnisse für die virtuellen Praktika verglichen mit den zuvor im Präsenzformat durchgeführten Praktika. Diese sehr positive Bewertung des digitalen Lehrangebots zeigte im Pandemieverlauf über die Dauer von zwei Semestern keine signifikante Änderung.
Schlussfolgerung: Die vorliegenden Daten belegen die hohe Akzeptanz eines digitalen Lehrangebots im Fach HNO-Heilkunde für Studierende. Auch wenn unerlässliche Bestandteile der ärztlichen Ausbildung, wie der Unterricht am Patienten und das Erlernen klinisch-praktischer Fertigkeiten, weiterhin nur im Präsenzformat realisiert werden können, legen die Ergebnisse nahe, dass digitale Elemente auch nach der SARS-CoV-2-Pandemie eine Rolle im Medizinstudium spielen könnten.
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.
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.
The first measurement of two-pion Bose–Einstein correlations in central Pb–Pb collisions at √sNN=2.76 TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.
Inclusive transverse momentum spectra of primary charged particles in Pb–Pb collisions at √sNN=2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0–5% and 70–80% of the hadronic Pb–Pb cross section. The measured charged particle spectra in |η|<0.8 and 0.3<pT<20 GeV/c are compared to the expectation in pp collisions at the same sNN, scaled by the number of underlying nucleon–nucleon collisions. The comparison is expressed in terms of the nuclear modification factor RAA. The result indicates only weak medium effects (RAA≈0.7) in peripheral collisions. In central collisions, RAA reaches a minimum of about 0.14 at pT=6–7 GeV/c and increases significantly at larger pT. The measured suppression of high-pT particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb–Pb collisions at the LHC.
The inclusive charged particle transverse momentum distribution is measured in proton–proton collisions at s=900 GeV at the LHC using the ALICE detector. The measurement is performed in the central pseudorapidity region (|η|<0.8) over the transverse momentum range 0.15<pT<10 GeV/c. The correlation between transverse momentum and particle multiplicity is also studied. Results are presented for inelastic (INEL) and non-single-diffractive (NSD) events. The average transverse momentum for |η|<0.8 is 〈pT〉INEL=0.483±0.001 (stat.)±0.007 (syst.) GeV/c and 〈pT〉NSD=0.489±0.001 (stat.)±0.007 (syst.) GeV/c, respectively. The data exhibit a slightly larger 〈pT〉 than measurements in wider pseudorapidity intervals. The results are compared to simulations with the Monte Carlo event generators PYTHIA and PHOJET.
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
Rapidity and transverse momentum dependence of inclusive J/ψ production in pp collisions at √s=7 TeV
(2011)
The ALICE experiment at the LHC has studied inclusive J/ψ production at central and forward rapidities in pp collisions at √s=7 TeV. In this Letter, we report on the first results obtained detecting the J/ψ through the dilepton decay into e+e− and μ+μ− pairs in the rapidity ranges |y|<0.9 and 2.5<y<4, respectively, and with acceptance down to zero pT. In the dielectron channel the analysis was carried out on a data sample corresponding to an integrated luminosity Lint=5.6 nb−1 and the number of signal events is NJ/ψ=352±32(stat.)±28(syst.); the corresponding figures in the dimuon channel are Lint=15.6 nb−1 and NJ/ψ=1924±77(stat.)±144(syst.). The measured production cross sections are σJ/ψ(|y|<0.9)=10.7±1.0(stat.)±1.6(syst.)−2.3+1.6(syst.pol.)μb and σJ/ψ(2.5<y<4)=6.31±0.25(stat.)±0.76(syst.)−1.96+0.95(syst.pol.)μb. The differential cross sections, in transverse momentum and rapidity, of the J/ψ were also measured.
Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at sqrt(s_NN)=130 GeV using the STAR TPC at RHIC. The elliptic flow signal, v_2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.