Search

The calcium isotopes are an ideal system to investigate the evolution of shell structure and magic numbers. Although the properties of surface nucleons in calcium have been well studied, probing the structure of deeply bound nucleons remains a challenge. Here, we report on the first measurement of unbound states in 53Ca and 55Ca, populated from 54,56Ca(p,pn) reactions at a beam energy of around 216 MeV/nucleon at the RIKEN Radioactive Isotopes Beam Factory. The resonance properties, partial cross sections, and momentum distributions of these unbound states were analyzed. Orbital angular momentum l assignments were extracted from momentum distributions based on calculations using the distorted wave impulse approximation (DWIA) reaction model. The resonances at excitation energies of 5516(41)keV in 53Ca and 6000(250)keV in 55Ca indicate a significant l =3 component, providing the first experimental evidence for the ν0f7/2 single-particle strength of unbound hole states in the neutron-rich Ca isotopes. The observed excitation energies and cross-sections point towards extremely localized and well separated strength distributions, with some fragmentation for the ν0f7/2 orbital in 55Ca. These results are in good agreement with predictions from shell-model calculations using the effective GXPF1Bs interaction and ab initio calculations and diverge markedly from the experimental distributions in the nickel isotones at Z=28.

Gamma decays were observed in 56Ca and 58Ca following quasi-free one-proton knockout reactions from 57,59Sc beams at ≈200 MeV/nucleon. For 56Ca, a γ ray transition was measured to be 1456(12) keV, while for 58Ca an indication for a transition was observed at 1115(34) keV. Both transitions were tentatively assigned as the 21+→0gs+ decays, and were compared to results from ab initio and conventional shell-model approaches. A shell-model calculation in a wide model space with a marginally modified effective nucleon-nucleon interaction depicts excellent agreement with experiment for 21+ level energies, two-neutron separation energies, and reaction cross sections, corroborating the formation of a new nuclear shell above the N = 34 shell. Its constituents, the 0f5/2 and 0g9/2 orbitals, are almost degenerate. This degeneracy precludes the possibility for a doubly magic 60Ca and potentially drives the dripline of Ca isotopes to 70Ca or even beyond.

States in the N=35 and 37 isotopes 55,57Ca have been populated by direct proton-induced nucleon removal reactions from 56,58Sc and 56Ca beams at the RIBF. In addition, the (p,2p) quasi-free single-proton removal reaction from 56Ca was studied. Excited states in 55K, 55Ca, and 57Ca were established for the first time via in-beam γ-ray spectroscopy. Results for the proton and neutron removal reactions from 56Ca to states in 55K and 55Ca for the level energies, excited state lifetimes, and exclusive cross sections agree well with state-of-the-art theoretical calculations using different approaches. The observation of a short-lived state in 57Ca suggests a transition in the calcium isotopic chain from single-particle dominated states at N=35 to collective excitations at N=37.

The proton drip-line nucleus 17Ne is investigated experimentally in order to determine its two-proton halo character. A fully exclusive measurement of the 17Ne(p,2p)16F→15⁎O+p quasi-free one-proton knockout reaction has been performed at GSI at around 500 MeV/nucleon beam energy. All particles resulting from the scattering process have been detected. The relevant reconstructed quantities are the angles of the two protons scattered in quasi-elastic kinematics, the decay of 16F into 15O (including γ decays from excited states) and a proton, as well as the 15O+p relative-energy spectrum and the 16F momentum distributions. The latter two quantities allow an independent and consistent determination of the fractions of l=0 and l=2 motion of the valence protons in 17Ne. With a resulting relatively small l=0 component of only around 35(3)%, it is concluded that 17Ne exhibits a rather modest halo character only. The quantitative agreement of the two values deduced from the energy spectrum and the momentum distributions supports the theoretical treatment of the calculation of momentum distributions after quasi-free knockout reactions at high energies by taking into account distortions based on the Glauber theory. Moreover, the experimental data allow the separation of valence-proton knockout and knockout from the 15O core. The latter process contributes with 11.8(3.1) mb around 40% to the total proton-knockout cross section of 30.3(2.3) mb, which explains previously reported contradicting conclusions derived from inclusive cross sections.

Jews who immigrated to the Canadian prairies before 1914 mostly gravitated to urban areas. Those who chose to farm usually located in Jewish agricultural colonies where a full Jewish life was possible. A minority voluntarily settled in small farming communities among non-Jews. Jewish merchants in prairie towns also became involved in agriculture both as farmers and as agricultural traders and dealers. Few Jews chose to settle on homesteads where they were isolated from Jewish social and religious life. In the interwar period, attempts to circumvent restrictions placed on Jewish immigration led Jewish philanthropic agencies to place Jewish refugee immigrants on scattered farms, often isolated from Jewish communities. Although economically unsuccessful the strategy achieved its humanitarian objectives.

Background: Cancer-associated thrombosis is a frequent complication in patients with malignancies. While factor XI (FXI)/FXIa inhibition is efficacious in preventing postoperative venous thromboembolism, its role in tumor cell-induced coagulation is less defined., Objectives: We thus aimed to provide mechanistic insights into FXI/FXIa inhibition in tumor cell-induced coagulation activation., Methods: Procoagulant activity (PCA) of 4 different tissue factor (TF) expressing tumor cell lines was analyzed by single-stage clotting and thrombin generation assay in the presence of a FXIa inhibitor, BMS-262084 (BMS), an inhibitory FXI antibody (anti-FXI), or peak and trough concentrations of rivaroxaban or tinzaparin. Further, tumor cell-induced platelet aggregation was recorded. Recombinant human TF served as positive control., Results: Although BMS and anti-FXI potently inhibited FXIa amidolytic activity, both inhibitors efficiently mitigated recombinant human TF- and tumor cell-induced fibrin clot formation and platelet aggregation only in the presence of low TF PCA. The anticoagulant effects showed an inverse correlation with the magnitude of cellular TF PCA expression. Similarly, BMS markedly interfered with tumor cell-induced thrombin generation, with the most prominent effects on peak and total thrombin. In addition, anticoagulant effects of FXIa inhibition by 10 μM BMS were in a similar range to those obtained by 600 nM rivaroxaban and 1.6 μM tinzaparin at low TF PCA levels. However, rivaroxaban and tinzaparin also exerted marked anticoagulant activity at high TF PCA levels., Conclusion: Our findings indicate that FXI/FXIa inhibition interferes with tumor cell-induced coagulation activation only at low TF PCA expression levels, a finding with potential implications for future in vivo studies., Competing Interests: Declaration of competing interests J.M., A.S., C.L., J.R., and L.B. declare no conflicts of interest relevant to the content of this article. C.C.R. has received travel support from Pfizer. M.V. declares personal fees for lectures from Bristol-Myers Squibb and travel support from Bayer, Bristol-Myers Squibb, and LEO Pharma. C.B. has received personal fees for consultancy, research support, and/or travel support from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Novartis, Pfizer, Roche, and Sanofi. F.L. has received personal fees for lectures or consultancy and/or research support from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, LEO Pharma, Pfizer, Sanofi, and Viatris., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

The neural mechanisms that unfold when humans form a large group defined by an overarching context, such as audiences in theater or sports, are largely unknown and unexplored. This is mainly due to the lack of availability of a scalable system that can record the brain activity from a significantly large portion of such an audience simultaneously. Although the technology for such a system has been readily available for a long time, the high cost as well as the large overhead in human resources and logistic planning have prohibited the development of such a system. However, during the recent years reduction in technology costs and size have led to the emergence of low-cost, consumer-oriented EEG systems, developed primarily for recreational use. Here by combining such a low-cost EEG system with other off-the-shelve hardware and tailor-made software, we develop in the lab and test in a cinema such a scalable EEG hyper-scanning system. The system has a robust and stable performance and achieves accurate unambiguous alignment of the recorded data of the different EEG headsets. These characteristics combined with small preparation time and low-cost make it an ideal candidate for recording large portions of audiences., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Introduction: Patients with acute myeloid leukemia (AML) are at increased risk of thrombohemorrhagic complications. Overexpressed tissue factor (TF) on AML blasts contributes to systemic coagulation activation. We have recently shown that the heme enzyme myeloperoxidase (MPO) negatively regulates TF procoagulant activity (PCA) on myelomonocytic cells in vitro. We now aimed to further characterize the functional interaction of MPO and TF in AML in vivo., Methods: We prospectively recruited 66 patients with newly diagnosed AML. TF PCA of isolated peripheral blood mononuclear cells (PBMC) was assessed by single-stage clotting assay in the presence or absence of inhibitors against MPO catalytic activity (ABAH) or against MPO-binding integrins (anti-CD18). MPO in plasma and in AML blasts was measured by ELISA, and plasma D-dimers and prothrombin fragment F1+2 were quantified by automated immunoturbidimetric and chemiluminescence assays, respectively., Results: Patients with AML had significantly higher MPO plasma levels compared to healthy controls and exhibited increased levels of D-dimers and F1+2. In vivo thrombin generation was mediated by TF PCA on circulating PBMC. Ex vivo incubation of isolated PBMC with ABAH or anti-CD18 antibody resulted in either increased or decreased TF PCA. The strong and robust correlation of F1+2 with TF PCA of circulating PBMC was abrogated at MPO plasma levels higher than 150 ng/mL, indicating a modulatory role for MPO on TF-mediated in vivo thrombin generation above this threshold., Conclusion: Our study indicates that catalytically active MPO released by circulating myeloblasts regulates TF-dependent coagulation in patients with newly diagnosed AML in a CD18-dependent manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aims: Pulmonary hypertension (PH) management is dependent on cardiac output (CO) assessment. The gold standard Fick method for CO and cardiac index (CI) measurement is not widely available. An accessible and reliable method for CO/CI estimation is needed not only in catheterization labs but also in other environments such as the intensive care unit, where pulmonary artery catheters are less likely to be used. We hypothesized that veno-arterial carbon dioxide gradient (PvaCO2) is a reliable surrogate for Fick CI in patients with PH., Methods and Results: A single-centre retrospective analysis of patients with PH who underwent direct Fick CI (DFCI) measurement during right heart catheterization. The primary outcome was correlation between PvaCO2 and DFCI. To assess the agreement between central and mixed venous CO2 values, a separate prospective cohort of patients was analysed. Data from 186 patients with all haemodynamic types of PH were analysed. PvaCO2 moderately correlated with Fick CI, R = -0.51 [95% confidence interval (CI): -0.61, -0.39]. A higher PvaCO2 was associated with an increased risk of CI < 2.5 L/min/m2 (odds ratio: 1.88, 95% CI: 1.55, 2.35). Low thermodilution CI with normal veno-arterial carbon dioxide gradient values was associated with a thermodilution underestimation of Fick CI. In the prospective analysis of 32 patients, central venous CO2 overestimated mixed venous values (mean difference 3.3, 95% CI: 2.5, 4.0) and there was poor agreement overall (limits of agreement -1.10, 7.59)., Conclusion: Veno-arterial carbon dioxide gradient moderately correlates with Fick CI and may be useful to identify patients with low CI. Central and mixed venous CO2 values should not be used interchangeably in PH., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The one-neutron knockout from ^{52}Ca in inverse kinematics onto a proton target was performed at ∼230  MeV/nucleon combined with prompt γ spectroscopy. Exclusive quasifree scattering cross sections to bound states in ^{51}Ca and the momentum distributions corresponding to the removal of 1f&#95;{7/2} and 2p&#95;{3/2} neutrons were measured. The cross sections, interpreted within the distorted-wave impulse approximation reaction framework, are consistent with a shell closure at the neutron number N=32, found as strong as at N=28 and N=34 in Ca isotopes from the same observables. The analysis of the momentum distributions leads to a difference of the root-mean-square radii of the neutron 1f&#95;{7/2} and 2p&#95;{3/2} orbitals of 0.61(23) fm, in agreement with the modified-shell-model prediction of 0.7 fm suggesting that the large root-mean-square radius of the 2p&#95;{3/2} orbital in neutron-rich Ca isotopes is responsible for the unexpected linear increase of the charge radius with the neutron number.

Introduction: Protein disulfide isomerase (PDI) contributes to tissue factor (TF) regulation in monocytes. While bacitracin and quercetin-3-rutinoside mitigate myeloid TF production, the effect of PACMA-31, a more specific PDI inhibitor with distinct pharmacologic properties, remains unclear., Materials and Methods: Lipopolysaccharide (LPS) stimulation of peripheral blood mononuclear cells (PBMCs) or citrate-anticoagulated whole blood was carried out in the presence of PACMA-31 or DMSO vehicle before monocytes were analyzed for TF expression, including antigen, procoagulant activity (PCA) and mRNA, release of IL-6 and TNFα, and LPS-induced signaling pathways., Results: While PACMA-31 alone had no effect, coincubation with LPS and PACMA-31 (25 μM) enhanced LPS-induced monocyte TF production in whole blood. The effect was at least partially regulated on the transcriptional level and could not be explained by increased phosphatidylserine membrane exposure. In contrast, the same PACMA-31 concentrations were cytotoxic in isolated PBMCs. A lower dose of PACMA-31, however, restored the stimulating effect by enhancing IκB-NFκB signaling that also increased the release of IL-6 and TNFα. The protease-activated receptor 2 (PAR2) inhibitor ENMD 547 but not TF antibody 10H10 or factor Xa inhibitor rivaroxaban prevented the stimulatory effect of PACMA-31 on inflammatory monocytes. In sharp contrast, short time incubation of LPS-stimulated PBMCs with 25 μM PACMA-31 was non-cytotoxic and significantly inhibited cellular TF PCA but not surface antigen expression., Conclusions: PACMA-31 regulates monocyte TF in a concentration-dependent manner by opposing transcriptional and posttranscriptional mechanisms. While low concentrations of PACMA-31 augment monocyte TF production by amplifying LPS-dependent PAR2 signaling, high concentrations convert monocyte TF into its non-coagulant state., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

A long-standing question in nuclear physics is whether chargeless nuclear systems can exist. To our knowledge, only neutron stars represent near-pure neutron systems, where neutrons are squeezed together by the gravitational force to very high densities. The experimental search for isolated multi-neutron systems has been an ongoing quest for several decades 1 , with a particular focus on the four-neutron system called the tetraneutron, resulting in only a few indications of its existence so far 2-4 , leaving the tetraneutron an elusive nuclear system for six decades. Here we report on the observation of a resonance-like structure near threshold in the four-neutron system that is consistent with a quasi-bound tetraneutron state existing for a very short time. The measured energy and width of this state provide a key benchmark for our understanding of the nuclear force. The use of an experimental approach based on a knockout reaction at large momentum transfer with a radioactive high-energy 8 He beam was key., (© 2022. The Author(s).)