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Institute
The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p-Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p-Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p–Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
Objective: The glucose stimulation of insulin secretion (GSIS) by pancreatic β-cells critically depends on increased production of metabolic coupling factors, including NADPH. Nicotinamide nucleotide transhydrogenase (NNT) typically produces NADPH at the expense of NADH and ΔpH in energized mitochondria. Its spontaneous inactivation in C57BL/6J mice was previously shown to alter ATP production, Ca2+ influx, and GSIS, thereby leading to glucose intolerance. Here, we tested the role of NNT in the glucose regulation of mitochondrial NADPH and glutathione redox state and reinvestigated its role in GSIS coupling events in mouse pancreatic islets.
Methods: Islets were isolated from female C57BL/6J mice (J-islets), which lack functional NNT, and genetically close C57BL/6N mice (N-islets). Wild-type mouse NNT was expressed in J-islets by adenoviral infection. Mitochondrial and cytosolic glutathione oxidation was measured with glutaredoxin 1-fused roGFP2 probes targeted or not to the mitochondrial matrix. NADPH and NADH redox state was measured biochemically. Insulin secretion and upstream coupling events were measured under dynamic or static conditions by standard procedures.
Results: NNT is largely responsible for the acute glucose-induced rise in islet NADPH/NADP+ ratio and decrease in mitochondrial glutathione oxidation, with a small impact on cytosolic glutathione. However, contrary to current views on NNT in β-cells, these effects resulted from a glucose-dependent reduction in NADPH consumption by NNT reverse mode of operation, rather than from a stimulation of its forward mode of operation. Accordingly, the lack of NNT in J-islets decreased their sensitivity to exogenous H2O2 at non-stimulating glucose. Surprisingly, the lack of NNT did not alter the glucose-stimulation of Ca2+ influx and upstream mitochondrial events, but it markedly reduced both phases of GSIS by altering Ca2+-induced exocytosis and its metabolic amplification.
Conclusion: These results drastically modify current views on NNT operation and mitochondrial function in pancreatic β-cells.
We provide the first comprehensive taxonomic revision of the poorly known South American butterfly genus Zischkaia Forster, 1964, hitherto regarded as including three described species. A phylogenetic analysis based on DNA sequence data shows that Zischkaia is monophyletic and consists of two morphologically diagnosable clades. Morphological characters and DNA 'barcodes' support the recognition of twelve species in the genus, a significant increase even for the relatively poorly studied subtribe Euptychiina. Consequently, nine new species are described and named herein, including Z. arctoa Nakahara, sp. nov., Z. chullachaki Nakahara & Zacca, sp. nov., Z. baku Zacca, Dolibaina & Dias, sp. nov., Z. arenisca Nakahara, Willmott & Hall, sp. nov., Z. argyrosflecha Nakahara, L. Miller & Huertas, sp. nov., Z. abanico Nakahara & Petit, sp. nov., Z. josti Nakahara & Kleckner, sp. nov., Z. mielkeorum Dolibaina, Dias & Zacca, sp. nov. and Z. warreni Dias, Zacca & Dolibaina, sp. nov. In addition, a neotype is designated for Satyrus pacarus Godart, [1824], and lectotypes are designated for Euptychia amalda Weymer, 1911, Euptychia fumata Butler, 1867 and Euptychia saundersii Butler, 1867.
A measurement of the production of prompt +c baryons in Pb–Pb collisions at √sNN = 5.02 TeV with the ALICE detector at the LHC is reported. The +c and − c were reconstructed at midrapidity (|y| < 0.5) via the hadronic decay channel +c → pK0 S (and charge conjugate) in the transverse momentum and centrality intervals 6 < pT < 12 GeV/c and 0–80%. The +c /D0 ratio, which is sensitive to the charm quark hadronisation mechanisms in the medium, is measured and found to be larger than the ratio measured in minimum-bias pp collisions at √s = 7 TeV and in p–Pb collisions at √sNN = 5.02 TeV. In particular, the values in p–Pb and Pb–Pb collisions differ by about two standard deviations of the combined statistical and systematic uncertainties in the common pT interval covered by the measurements in the two collision systems. The + c /D0 ratio is also compared with model calculations including different implementations of charm quark hadronisation. The measured ratio is reproduced by models implementing a pure coalescence scenario, while adding a fragmentation contribution leads to an underestimation. The + c nuclear modification factor, RAA, is also presented. The measured values of the RAA of + c , D+ s and non-strange D mesons are compatible within the combined statistical and systematic uncertainties. They show, however, a hint of a hierarchy (RD0 AA < RD+ s AA < R+ c AA ), conceivable with a contribution from coalescence mechanisms to charm hadron formation in the medium.
The jet radial structure and particle transverse momentum (pT) composition within jets are presented in centrality-selected Pb–Pb collisions at √sNN = 2.76 TeV. Track-based jets, which are also called charged jets, were reconstructed with a resolution parameter of R = 0.3 at midrapidity |ηch jet| < 0.6 for transverse momenta pT, ch jet = 30–120 GeV/c. Jet–hadron correlations in relative azimuth and pseudorapidity space (Δϕ, Δη) are measured to study the distribution of the associated particles around the jet axis for different pT,assoc-ranges between 1 and 20 GeV/c. The data in Pb–Pb collisions are compared to reference distributions for pp collisions, obtained using embedded PYTHIA simulations. The number of high-pT associate particles (4 < pT,assoc < 20 GeV/c) in Pb–Pb collisions is found to be suppressed compared to the reference by 30 to 10% depending on centrality. The radial particle distribution relative to the jet axis shows a moderate modification in Pb–Pb collisions with respect to PYTHIA. High-pT associate particles are slightly more collimated in Pb–Pb collisions compared to the reference, while low-pT associate particles tend to be broadened. The results, which are presented for the first time down to pT, ch jet = 30 GeV/c in Pb–Pb collisions, are compatible with both previous jet–hadron-related measurements from the CMS Collaboration and jet shape measurements from the ALICE Collaboration at higher pT, and add further support for the established picture of in-medium parton energy loss.
Study of the Λ–Λ interaction with femtoscopy correlations in pp and p–Pb collisions at the LHC
(2019)
This work presents new constraints on the existence and the binding energy of a possible – bound state, the H-dibaryon, derived from – femtoscopic measurements by the ALICE collaboration. The results are obtained from a new measurement using the femtoscopy technique in pp collisions at √s = 13 TeV and p–Pb collisions at √sNN = 5.02 TeV, combined with previously published results from pp collisions at √s = 7 TeV. The – scattering parameter space, spanned by the inverse scattering length f −1 0 and the effective range d0, is constrained by comparing the measured – correlation function with calculations obtained within the Lednický model. The data are compatible with hypernuclei results and lattice computations, both predicting a shallow attractive interaction, and permit to test different theoretical approaches describing the – interaction. The region in the (f −1 0 ,d0) plane which would accommodate a – bound state is substantially restricted compared to previous studies. The binding energy of the possible – bound state is estimated within an effective-range expansion approach and is found to be B = 3.2+1.6 −2.4(stat)+1.8 −1.0(syst) MeV.
Loss of the tumor suppressor Pdcd4 was reported for various tumor entities and proposed as a prognostic marker in tumorigenesis. We previously characterized decreased Pdcd4 protein stability in response to mitogenic stimuli, which resulted from p70S6K1-dependent protein phosphorylation, β-TrCP1-mediated ubiquitination, and proteasomal destruction. Following high-throughput screening of natural product extract libraries using a luciferase-based reporter assay to monitor phosphorylation-dependent proteasomal degradation of the tumor suppressor Pdcd4, we succeeded in showing that a crude extract from Eriophyllum lanatum stabilized Pdcd4 from TPA-induced degradation. Erioflorin was identified as the active component and inhibited not only degradation of the Pdcd4-luciferase-based reporter but also of endogenous Pdcd4 at low micromolar concentrations. Mechanistically, erioflorin interfered with the interaction between the E3-ubiquitin ligase β-TrCP1 and Pdcd4 in cell culture and in in vitro binding assays, consequently decreasing ubiquitination and degradation of Pdcd4. Interestingly, while erioflorin stabilized additional β-TrCP-targets (such as IκBα and β-catenin), it did not prevent the degradation of targets of other E3-ubiquitin ligases such as p21 (a Skp2-target) and HIF-1α (a pVHL-target), implying selectivity for β-TrCP. Moreover, erioflorin inhibited the tumor-associated activity of known Pdcd4- and IκBα-regulated αtranscription factors, that is, AP-1 and NF-κB, altered cell cycle progression and suppressed proliferation of various cancer cell lines. Our studies succeeded in identifying erioflorin as a novel Pdcd4 stabilizer that inhibits the interaction of Pdcd4 with the E3-ubiquitin ligase β-TrCP1. Inhibition of E3-ligase/target-protein interactions may offer the possibility to target degradation of specific proteins only as compared to general proteasome inhibition.
In this letter, the production of deuterons and anti-deuterons in pp collisions at √s = 7 TeV is studied as a function of the charged-particle multiplicity density at mid-rapidity with the ALICE detector at the LHC. Production yields are measured at mid-rapidity in five multiplicity classes and as a function of the deuteron transverse momentum (pT). The measurements are discussed in the context of hadron–coalescence models. The coalescence parameter B2, extracted from the measured spectra of (anti-)deuterons and primary (anti-)protons, exhibits no significant pT-dependence for pT < 3 GeV/c, in agreement with the expectations of a simple coalescence picture. At fixed transverse momentum per nucleon, the B2 parameter is found to decrease smoothly from low multiplicity pp to Pb–Pb collisions, in qualitative agreement with more elaborate coalescence models. The measured mean transverse momentum of (anti-)deuterons in pp is not reproduced by the Blast-Wave model calculations that simultaneously describe pion, kaon and proton spectra, in contrast to central Pb–Pb collisions. The ratio between the pT-integrated yield of deuterons to protons, d/p, is found to increase with the chargedparticle multiplicity, as observed in inelastic pp collisions at different centre-of-mass energies. The d/p ratios are reported in a wide range, from the lowest to the highest multiplicity values measured in pp collisions at the LHC.
Matsucoccus krystalae Ahmed and Miller, new species, (Hemiptera:Coccomorpha: Matsucoccidae) is described based on morphological characters of adult females and third-instar males. We designate the lectotype of Matsucoccus alabamae Morrison. Matsucoccus alabamae Morrison and M. gallicolus Morrison are redescribed, also based on adult females and third-instar males. Detailed illustrations and descriptions are presented for each species and an identification key for the five species occurring in the eastern U.S. is provided. Analysis of 18S, 28S D2/D3, and 28S D10 loci were performed to support morphological determination. Barcodes using 5′ COI of M. alabamae and M. krystalae were generated, the first such data from authoritatively identified Matsucoccus species. Of particular interest is that most of the specimens in the study were taken in Lindgren funnel traps.
Fire is an integral component of many ecosystems worldwide. Many plant species require fire-related cues, primarily heat and smoke, to trigger germination. Despite the importance of this process, the responses of many Australian species to these cues are unknown. Without this knowledge fire management strategies may be developed that are inappropriate for individual species and vegetation communities. In this study we examined the responses of a dry sclerophyll forest seed bank to heat and smoke germination cues. Analysis was possible for 48 taxa within the soil seedbank with 34 of these showing a response to one or both of the germination cues. 10 species responded to the heat treatment, 11 species responded to the smoke treatment and 13 species responded to both the heat and smoke treatments. Germination cues acted independently for all species considered. Results in this study were consistent with published reports for most species, although some differences were seen at the species and genus level. The study highlights the importance of fire-related cues in enhancing germination of a large proportion of the species occurring in dry sclerophyll forests.
The Kinase Chemogenomic Set (KCGS): an open science resource for kinase vulnerability identification
(2021)
We describe the assembly and annotation of a chemogenomic set of protein kinase inhibitors as an open science resource for studying kinase biology. The set only includes inhibitors that show potent kinase inhibition and a narrow spectrum of activity when screened across a large panel of kinase biochemical assays. Currently, the set contains 187 inhibitors that cover 215 human kinases. The kinase chemogenomic set (KCGS), current Version 1.0, is the most highly annotated set of selective kinase inhibitors available to researchers for use in cell-based screens.
Targeting self-renewal and tumorigenicity has been proposed as a potential strategy against cancer stem cells (CSCs). Epigenetic proteins are key modulators of gene expression and cancer development contributing to regulation and maintenance of self-renewal and tumorigenicity. Here, we have screened a small-molecule epigenetic inhibitor library using 3D in vitro models in order to determine potential epigenetic targets associated with self-renewal and tumorigenicity in Canine Mammary Cancer (CMC) cells. We identified inhibition of BET proteins as a promising strategy to inhibit CMC colonies and tumorspheres formation. Low doses of (+)-JQ1 were able to downregulate important genes associated to self-renewal pathways such as WNT, NOTCH, Hedgehog, PI3K/AKT/mTOR, EGF receptor and FGF receptor in CMC tumorspheres. In addition, we observed downregulation of ZEB2, a transcription factor important for the maintenance of self-renewal in canine mammary cancer cells. Furthermore, low doses of (+)-JQ1 were not cytotoxic in CMC cells cultured in 2D in vitro models but induced G2/M cell cycle arrest accompanied by upregulation of G2/M checkpoint-associated genes including BTG2 and CCNG2. Our work indicates the BET inhibition as a new strategy for canine mammary cancers by modulating the self-renewal phenotype in tumorigenic cells such as CSCs.
The ALICE collaboration performed the first rapidity-differential measurement of coherent J/ψ photoproduction in ultra-peripheral Pb–Pb collisions at a center-of-mass energy √sNN = 5.02 TeV. The J/ψ is detected via its dimuon decay in the forward rapidity region (−4.0 < y < −2.5) 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 750 μb−1. The cross section for coherent J/ψ production is presented in six rapidity bins. The results are compared with theoretical models for coherent J/ψ photoproduction. These comparisons indicate that gluon shadowing effects play a role in the photoproduction process. The ratio of ψ to J/ψ coherent photoproduction cross sections was measured and found to be consistent with that measured for photoproduction off protons.
Multiplicity dependence of light (anti-)nuclei production in p–Pb collisions at √sNN =5.02 TeV
(2020)
The measurement of the deuteron and anti-deuteron production in the rapidity range −1 < y < 0 as a function of transverse momentum and event multiplicity in p–Pb collisions at √sNN = 5.02 TeV is presented. (Anti-)deuterons are identified via their specific energy loss dE/dx and via their time-offlight. Their production in p–Pb collisions is compared to pp and Pb–Pb collisions and is discussed within the context of thermal and coalescence models. The ratio of integrated yields of deuterons to protons (d/p) shows a significant increase as a function of the charged-particle multiplicity of the event starting from values similar to those observed in pp collisions at low multiplicities and approaching those observed in Pb–Pb collisions at high multiplicities. The mean transverse particle momenta are extracted from the deuteron spectra and the values are similar to those obtained for p and particles. Thus, deuteron spectra do not follow mass ordering. This behaviour is in contrast to the trend observed for non-composite particles in p–Pb collisions. In addition, the production of the rare 3He and 3He nuclei has been studied. The spectrum corresponding to all non-single diffractive p-Pb collisions is obtained in the rapidity window −1 < y < 0 and the pT-integrated yield dN/dy is extracted. It is found that the yields of protons, deuterons, and 3He, normalised by the spin degeneracy factor, follow an exponential decrease with mass number.
The ALICE collaboration at the CERN LHC reports novel measurements of jet substructure in pp collisions at √s = 7 TeV and central Pb–Pb collisions at √sNN = 2.76 TeV. Jet substructure of track-based jets is explored via iterative declustering and grooming techniques. We present the measurement of the momentum sharing of two-prong substructure exposed via grooming, the zg, and its dependence on the opening angle, in both pp and Pb–Pb collisions. We also present the measurement of the distribution of the number of branches obtained in the iterative declustering of the jet, which is interpreted as the number of its hard splittings. In Pb–Pb collisions, we observe a suppression of symmetric splittings at large opening angles and an enhancement of splittings at small opening angles relative to pp collisions, with no significant modification of the number of splittings. The results are compared to predictions from various Monte Carlo event generators to test the role of important concepts in the evolution of the jet in the medium such as colour coherence.
Aims: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk.
Methods and results: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies.
In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95–1.02) in group A, 0.98 (0.93–1.04) in group B, and 0.95 (0.89–1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07–1.23) in group A, 1.13 (1.05–1.22) in group B, and 1.12 (1.05–1.20) in group C.
Conclusions: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.
Two-particle correlation functions were measured for pp, p, p, and pairs in Pb–Pb collisions at √sNN = 2.76 TeV and √sNN = 5.02 TeV recorded by the ALICE detector. From a simultaneous fit to all obtained correlation functions, real and imaginary components of the scattering lengths, as well as the effective ranges, were extracted for combined p and p pairs and, for the first time, for pairs. Effective averaged scattering parameters for heavier baryon–antibaryon pairs, not measured directly, are also provided. The results reveal similarly strong interaction between measured baryon–antibaryon pairs, suggesting that they all annihilate in the same manner at the same pair relative momentum k∗. Moreover, the reported significant non-zero imaginary part and negative real part of the scattering length provide motivation for future baryon–antibaryon bound state searches.