We briefly report on the recent heavy-ion measurements performed by the LHCb collaboration. An interesting variety of results are presented, such as the measurement of promptly produced charged ...particles in pp and pPb collisions, the cross-section ratio χc2 over χc1 in pPb and the measurement of coherent J/ψ in peripheral and ultra-peripheral PbPb collisions.
LHCb is one of the four main experiments running at the Large Hadron Collider (LHC) of the European Organization for Nuclear Research. Since 2010, it has been collecting data to study the Physics of ...b and c quarks. For the past three years, the experimental apparatus underwent significant upgrades to be ready for a new round of data collection, expected to start in June 2022. The new apparatus is designed to be able to run at an instantaneous luminosity five times larger than the previous one, which was 2.0×1032 cm−2s−1, and the whole detector readout will be at a 40 MHz rate. It is worth noticing that the luminosity at the LHCb interaction point, for the characteristics of the detector, needs to be reduced with respect to the luminosity provided by LHC. Major changes in the different subdetectors were required, along with complete modifications of the trigger schemes. The LHCb collaboration is developing and studying different methods for the on-line measurement of luminosity at the LHCb impact point, crucial for the monitoring of correct machine operation and for most experimental physics studies. The present work describes a procedure based on hit counting in the muon detector for an on-line luminosity monitor. The performance and the precision achieved with this method in tests carried out on past data collected are presented, together with proposals for future upgrades.
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•Diabetes increases the expression of PTP1B and markers of ERS in human vessels.•ERS induces endothelial dysfunction via activation of the p38/JNK signaling pathway.•Deficiency in ...endothelial PTP1B protects from ERS-induced endothelial dysfunction.•Deletion of endothelial PTP1B prevents from diabetes-induced endothelial dysfunction.
Diabetes notably increases the risk for endothelial dysfunction, a main precursor for microvascular complications. While endoplasmic reticulum stress (ERS) and protein tyrosine phosphatase 1B (PTP1B) have been associated with endothelial dysfunction in resistance vessels, whether these mechanisms also contribute to diabetes-mediated endothelial dysfunction in conduit arteries remains unknown. Herein, we tested the hypothesis that diabetes induces macrovascular endothelial dysfunction via endothelial ERS-induced, PTP1B-mediated apoptosis. We showed that diabetes concomitantly increased the expression of PTP1B and of markers of ERS, including GRP78, XBP1, splXBP1 and CHOP in human vessels. Exposure of aortic rings from wild-type mice to the ERS inducers tunicamycin and thapsigargin markedly reduced endothelium-dependent relaxation. Global and endothelial-specific deletion of PTP1B as well as pharmacological inhibition protected aortic rings from ERS-mediated endothelial dysfunction. Nitric oxide synthase inhibition with l-NAME abolished relaxation in the presence and absence of ERS, but neither reactive oxygen species scavenging with tempol or peg-catalase, nor cyclooxygenase inhibition with indomethacin prevented ERS-mediated endothelial dysfunction. However, both p38-MAPK and JNK inhibition protected aortic rings from ERS-mediated endothelial dysfunction. In HUVECs, PTP1B deletion prevented ERS-induced PARP cleavage and apoptosis. Lastly, acute ERS inhibition in aortic rings and selective deficiency of endothelial PTP1B in mice protected mice from diabetes-induced endothelial dysfunction. Altogether, these data support the contribution of the p38/JNK-apoptosis pathway in ERS-mediated endothelial dysfunction and present endothelial PTP1B as a major regulator of endothelial cell viability in conduit vessels and a potential target for the management of macrovascular diseases in diabetes.
OBJECTIVETo evaluate the effect of liver transplantation (LT) in patients with Wilson disease (WD) with severe neurologic worsening resistant to active chelation.
METHODSFrench patients with WD who ...underwent LT for pure neurologic indication were retrospectively studied. Before LT and at the last follow-up, neurologic impairment was evaluated with the Unified Wilsonʼs Disease Rating Scale (UWDRS) score, disability with the modified Rankin Scale (mRS) score, and hepatic function with the Model for End-stage Liver Disease score, together with the presence of a Kayser-Fleischer ring (KFR), brain MRI scores, and copper balance. The survival rate and disability at the last follow-up were the coprimary outcomes; evolution of KFR and brain MRI were the secondary outcomes. Prognosis factors were further assessed.
RESULTSEighteen patients had LT. All were highly dependent before LT (median mRS score 5). Neurologic symptoms were severe (median UWDRS score 105), dominated by dystonia and parkinsonism. The cumulated survival rate was 88.8% at 1 year and 72.2% at 3 and 5 years. At the last follow-up, 14 patients were alive. Their mRS and UWDRS scores improved (p < 0.0001 and p = 0.0003). Eight patients had a major improvement (78% decrease of the UWDRS score), 4 a moderate one (41% decrease), and 2 a stable status. KFR and brain MRI scores improved (p = 0.0007). Severe sepsis (p = 0.011) and intensive care unit admission (p = 0.001) before LT were significantly associated with death.
CONCLUSIONSLT is a rescue therapeutic option that should be carefully discussed in selected patients with neurologic WD resistant to anticopper therapies (chelators or zinc salts) as it might allow patients to gain physical independency with a reasonable risk.
CLASSIFICATION OF EVIDENCEThis study provides Class IV evidence that for patients with WD with severe neurologic worsening resistant to active pharmacologic therapy, LT might decrease neurologic impairment.
While adult pancreatic stem cells are thought not to exist, it is now appreciated that the acinar compartment harbors progenitors, including tissue-repairing facultative progenitors (FPs). Here, we ...study a pancreatic acinar population marked by trefoil factor 2 (Tff2) expression. Long-term lineage tracing and single-cell RNA sequencing (scRNA-seq) analysis of Tff2-DTR-CreER
-targeted cells defines a transit-amplifying progenitor (TAP) population that contributes to normal homeostasis. Following acute and chronic injury, Tff2
cells, distinct from FPs, undergo depopulation but are eventually replenished. At baseline, oncogenic Kras
-targeted Tff2
cells are resistant to PDAC initiation. However, Kras
activation in Tff2
cells leads to survival and clonal expansion following pancreatitis and a cancer stem/progenitor cell-like state. Selective ablation of Tff2
cells prior to Kras
activation in Mist1
acinar or Dclk1
FP cells results in enhanced tumorigenesis, which can be partially rescued by adenoviral Tff2 treatment. Together, Tff2 defines a pancreatic TAP population that protects against Kras-driven carcinogenesis.
Background
The US National Institutes of Mental Health Research Domain Criteria (RDoC) seek to stimulate research into biologically validated neuropsychological dimensions across mental illness ...symptoms and diagnoses. The RDoC framework comprises 39 functional constructs designed to be revised and refined, with the overall goal of improving diagnostic validity and treatments. This study aimed to reach a consensus among experts in the addiction field on the ‘primary’ RDoC constructs most relevant to substance and behavioural addictions.
Methods
Forty‐four addiction experts were recruited from Australia, Asia, Europe and the Americas. The Delphi technique was used to determine a consensus as to the degree of importance of each construct in understanding the essential dimensions underpinning addictive behaviours. Expert opinions were canvassed online over three rounds (97% completion rate), with each consecutive round offering feedback for experts to review their opinions.
Results
Seven constructs were endorsed by ≥ 80% of experts as ‘primary’ to the understanding of addictive behaviour: five from the Positive Valence System (reward valuation, expectancy, action selection, reward learning, habit); one from the Cognitive Control System (response selection/inhibition); and one expert‐initiated construct (compulsivity). These constructs were rated to be related differentially to stages of the addiction cycle, with some linked more closely to addiction onset and others more to chronicity. Experts agreed that these neuropsychological dimensions apply across a range of addictions.
Conclusions
The study offers a novel and neuropsychologically informed theoretical framework, as well as a cogent step forward to test transdiagnostic concepts in addiction research, with direct implications for assessment, diagnosis, staging of disorder, and treatment.
The NOx pollution produced by road traffic in confined volumes, such as tunnels, is an issue for public health. This work focuses on the mechanisms of NOx removal by modified cement pastes. The ...samples (made of pure synthetic powders or cement paste cylinders) are continuously exposed to 220ppbv of NO and/or 110ppbv of NO2 gas. The ability for the main hydrates (such as Ca(OH)2 and C–S–H) to trap NO2 is then quantified. After the leaching of samples, the chromatography experiments show that the adsorbed NO2 is transformed in nitrate and nitrite ions by a disproportionate mechanism. The addition of activated carbon into cement paste enhances the NO2 abatement, which is not influenced by carbonation. The NO2 abatement by the activated carbon materials is also stable between 20 and 50°C, revealing a competition between the disproportionate reaction and the gas adsorption.
•Ca(OH)2 and C–S–H degrade NO2 in nitrate and nitrite via a disproportionate reaction.•The high surface area of activated carbon boosts the NO2 fixation in cement paste.•Disproportionate reaction competes with adsorption in presence of activated carbon.•The NO2 abatement by the activated carbon material remains stable between 20 and 50°C.•The NO2 abatement by the activated carbon material is not affected by carbonation.