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We report new STAR measurements of the single-spin asymmetries 𝐴𝐿 for 𝑊+ and 𝑊− bosons produced in polarized proton-proton collisions at √𝑠=510 GeV as a function of the decay-positron and decay-electron pseudorapidity. The data were obtained in 2013 and correspond to an integrated luminosity of 250 pb−1. The results are combined with previous results obtained with 86 pb−1. A comparison with theoretical expectations based on polarized lepton-nucleon deep-inelastic scattering and prior polarized proton-proton data suggests a difference between the ¯𝑢 and ¯𝑑 quark helicity distributions for 0.05<𝑥<0.25. In addition, we report new results for the double-spin asymmetries 𝐴𝐿𝐿 for 𝑊±, as well as 𝐴𝐿 for 𝑍/𝛾* production and subsequent decay into electron-positron pairs.
Lattice QCD investigation of a doubly-bottom b̄b̄ud tetraquark with quantum numbers I(JP) = 0(1⁺)
(2019)
We use lattice QCD to investigate the spectrum of the ¯𝑏¯𝑏𝑢𝑑 four-quark system with quantum numbers 𝐼(𝐽𝑃)=0(1+). We use five different gauge-link ensembles with 2+1 flavors of domain-wall fermions, including one at the physical pion mass, and treat the heavy ¯𝑏 quark within the framework of lattice nonrelativistic QCD. Our work improves upon previous similar computations by considering in addition to local four-quark interpolators also nonlocal two-meson interpolators and by performing a Lüscher analysis to extrapolate our results to infinite volume. We obtain a binding energy of (−128±24±10) MeV, corresponding to the mass (10476±24±10) MeV, which confirms the existence of a ¯𝑏¯𝑏𝑢𝑑 tetraquark that is stable with respect to the strong and electromagnetic interactions.
Measurement of branching fractions for D meson decaying into ϕ meson and a pseudoscalar meson
(2019)
The four decay modes D0 → φπ0, D0 → φη, D+ → φπ+, and D+ → φK + are studied by using a data sample taken at the centre-of-mass energy √s = 3.773 GeV with the BESIII detector, corresponding to an integrated luminosity of 2.93 fb−1. The branching fractions of the first three decay modes are measured to be B(D0 → φπ0) = (1.168 ± 0.028 ± 0.028) × 10−3, B(D0 → φη) = (1.81 ± 0.46 ± 0.06) × 10−4, and B(D+ → φπ+) = (5.70 ± 0.05 ± 0.13) × 10−3, respectively, where the first uncertainties are statistical and the second are systematic. In addition, the upper limit of the branching fraction for D+ → φK+ is given to be 2.1 × 10−5 at the 90% confidence level. The ratio of B(D0 → φπ0) to B(D+ → φπ+) is calculated to be (20.49 ± 0.50 ± 0.45)%, which is consistent with the theoretical prediction based on isospin symmetry between these two decay modes.
Using a data sample with an integrated luminosity of 2.93 fb−1 taken at the center-of-mass energy of 3.773 GeV, we search for the Majorana neutrino (𝜈𝑚) in the lepton number violating decays 𝐷→𝐾𝜋𝑒+𝑒+. No significant signal is observed, and the upper limits on the branching fraction at the 90% confidence level are set to be ℬ(𝐷0→𝐾−𝜋−𝑒+𝑒+)<2.8×10−6, ℬ(𝐷+→𝐾0𝑆𝜋−𝑒+𝑒+)<3.3×10−6 and ℬ(𝐷+→𝐾−𝜋0𝑒+𝑒+)<8.5×10−6. The Majorana neutrino is searched for with different mass assumptions ranging from 0.25 to 1.0 GeV/𝑐2 in the decays 𝐷0→𝐾−𝑒+𝜈𝑚,𝜈𝑚→𝜋−𝑒+ and 𝐷+→𝐾0𝑆𝑒+𝜈𝑚,𝜈𝑚→𝜋−𝑒+, and the upper limits on the branching fraction at the 90% confidence level are at the level of 10−7∼10−6, depending on the mass of the Majorana neutrino. The constraints on the mixing matrix element |𝑉𝑒𝜈𝑚|2 are also evaluated.
We study the electromagnetic Dalitz decay 𝐽/𝜓→𝑒+𝑒−𝜂 and search for dielectron decays of a dark gauge boson (𝛾′) in 𝐽/𝜓→𝛾′𝜂 with the two 𝜂 decay modes 𝜂→𝛾𝛾 and 𝜂→𝜋+𝜋−𝜋0 using (1310.6±7.0)×106 𝐽/𝜓 events collected with the BESIII detector. The branching fraction of 𝐽/𝜓→𝑒+𝑒−𝜂 is measured to be (1.43±0.04(stat)±0.06(syst))×10−5, with a precision that is improved by a factor of 1.5 over the previous BESIII measurement. The corresponding dielectron invariant mass dependent modulus square of the transition form factor is explored for the first time, and the pole mass is determined to be Λ=2.84±0.11(stat)±0.08(syst) GeV/𝑐2. We find no evidence of 𝛾′ production and set 90% confidence level upper limits on the product branching fraction ℬ(𝐽/𝜓→𝛾′𝜂)×ℬ(𝛾′→𝑒+𝑒−) as well as the kinetic mixing strength between the standard model photon and 𝛾′ in the mass range of 0.01≤𝑚𝛾′≤2.4 GeV/𝑐2.
b̄b̄ud tetraquark resonances in the Born-Oppenheimer approximation using lattice QCD potentials
(2019)
We study tetraquark resonances for a pair of static antiquarks b¯b¯ in presence of two light quarks ud based on lattice QCD potentials. The system is treated in the Born-Oppenheimer approximation and we use the emergent wave method. We focus on the isospin I = 0 channel but take different angular momenta l of the heavy antiquarks b¯b¯ into account. Further calculations have already predicted a bound state for the l = 0 case with quantum numbers I(JP) = 0(1+). Performing computations for several angular momenta, we extract the phase shifts and search for T and S matrix poles in the second Riemann sheet. For angular momentum l = 1, we predict a tetraquark resonance with quantum numbers I(JP) = 0(1−), resonance mass m = 10576+4−4 MeV and decay width Γ = 112+90−103 MeV, which decays into two B mesons.
Using 𝑒+𝑒−→Λ+𝑐¯Λ−𝑐 production from a 567 pb−1 data sample collected by BESIII at 4.6 GeV, a full angular analysis is carried out simultaneously on the four decay modes of Λ+𝑐→𝑝𝐾0𝑆, Λ𝜋+, Σ+𝜋0, and Σ0𝜋+. For the first time, the Λ+𝑐 transverse polarization is studied in unpolarized 𝑒+𝑒− collisions, where a nonzero effect is observed with a statistical significance of 2.1𝜎. The decay asymmetry parameters of the Λ+𝑐 weak hadronic decays into 𝑝𝐾0𝑆, Λ𝜋+, Σ+𝜋0 and Σ0𝜋+ are measured to be 0.18±0.43(stat)±0.14(syst), −0.80±0.11(stat)±0.02(syst), −0.57±0.10(stat)±0.07(syst), and −0.73±0.17(stat)±0.07(syst), respectively. In comparison with previous results, the measurements for the Λ𝜋+ and Σ+𝜋0 modes are consistent but with improved precision, while the parameters for the 𝑝𝐾0𝑆 and Σ0𝜋+ modes are measured for the first time.
We measure the Born cross sections of the process 𝑒+𝑒−→𝐾+𝐾−𝐾+𝐾− at center-of-mass (c.m.) energies, √𝑠, between 2.100 and 3.080 GeV. The data were collected using the BESIII detector at the BEPCII collider. An enhancement at √𝑠=2.232 GeV is observed, very close to the 𝑒+𝑒−→Λ¯Λ production threshold. A similar enhancement at the same c.m. energy is observed in the 𝑒+𝑒−→𝜙𝐾+𝐾− cross section. The energy dependence of the 𝐾+𝐾−𝐾+𝐾− and 𝜙𝐾+𝐾− cross sections differs significantly from that of 𝑒+𝑒−→𝜙𝜋+𝜋−.
Soil-Transmitted Helminths (STH) is a group of nematodes that infect people and transmitted through soil media. STH occurs especially among pre-school and school-aged children, and commonly related to environmental sanitation and personal hygiene. The study objected to determine the factors related to the incidence of STH in children 5-15 years who lived surrounding the Sukawinatan district of Palembang city. The observational analytic using the cross-sectional design, consisted of 110 subjects sampled by consecutive sampling. Data on environmental sanitation and personal hygiene were obtained by questionnaires, while infection status using the Kato-Katz faecal technic. The results were analyzed using Chi-square test (α = 0.05), showed that 24.5% of population where infected with STH. A number of 1-24-2 children were infected with hookworm-Ascaris lumbricoides-Trichuris trichiura infection, respectively. Based on statistical test results, the association of STH infection with variables were: waste disposal (p = 0.268), water facilities (p = 1.000), sewage disposal (p = 0.224), latrine (p = 0.021), hand washing prior to meal (p = 0.001), hand washing after defecate (p = 0.028), use of footwear (p = 0.013), and nail hygiene (p = 1.000). Concluded that the significant factors related to STH were use of latrine, hand washing behaviour, and use of footwear. Further research will be necessary to successfully eliminate this neglected tropical disease.
The time-dependent Schrödinger equation for quadratic Hamiltonians has Gaussian wave packets as exact solutions. For the parametric oscillator with frequency ω(t), the width of these wave packets must be time-dependent. This time-dependence can be determined by solving a complex nonlinear Riccati equation or an equivalent real nonlinear Ermakov equation. All quantum dynamical properties of the system can easily be constructed from these solutions, e.g., uncertainties of position and momentum, their correlations, ground state energies, etc. In addition, the link to the corresponding classical dynamics is supplied by linearizing the Riccati equation to a complex Newtonian equation, actually representing two equations of the same kind: one for the real and one for the imaginary part. If the solution of one part is known, the missing (linear independent) solution of the other can be obtained via a conservation law for the motion in the complex plane. Knowing these two solutions, the solution of the Ermakov equation can be determined immediately plus the explicit expressions for all the quantum dynamical properties mentioned above. The effect of a dissipative, linear velocity dependent friction force on these systems is discussed.
Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development.
A remarkable part of children’ s development and education happens in educational institutions. Acoustic environments in these institutions are usually highly complex and noisy, hence it is demanding to identify relevant target speakers and to ignore irrelevant sounds. Previous research has analyzed auditory selective attention in adults, both in dichotic and binaural listening environments. Until now, there is little knowledge of auditory selective attention in children. In the present work, the original paradigm was adapted by using a task suited for children which included child-oriented elements. Further, the subject’s anthropometric sizes were considered for an aurally-accurate reproduction of the acoustic scene. Twenty-four adults and twenty-four children participated in an experiment on auditory selective attention. Noise and noise-free conditions and various target-distractor distributions in the room were analyzed among others. The result of this experiment revealed significant differences between adults and children, especially in the way auditory attention was influenced by noise.
Cannabis is the most commonly used illicit drug in the world. However, because of a changing legal landscape and rising interest in therapeutic utility, there is an increasing trend in (long-term) use and possibly cannabis impairment. Importantly, a growing body of evidence suggests that regular cannabis users develop tolerance to the impairing, as well as the rewarding, effects of the drug. However, the neuroadaptations that may underlie cannabis tolerance remain unclear. Therefore, this double-blind, randomized, placebo-controlled, cross-over study assessed the acute influence of cannabis on the brain and behavioral outcomes in two distinct cannabis user groups. Twelve occasional and 12 chronic cannabis users received acute doses of cannabis (300-μg/kg delta-9-tetrahydrocannabinol) and placebo and underwent ultrahigh field functional magnetic resonance imaging and magnetic resonance spectroscopy. In occasional users, cannabis induced significant neurometabolic alterations in reward circuitry, namely, decrements in functional connectivity and increments in striatal glutamate concentrations, which were associated with increases in subjective high and decreases in performance on a sustained attention task. Such changes were absent in chronic users. The finding that cannabis altered circuitry and distorted behavior in occasional, but not chronic users, suggests reduced responsiveness of the reward circuitry to cannabis intoxication in chronic users. Taken together, the results suggest a pharmacodynamic mechanism for the development of tolerance to cannabis impairment, of which is important to understand in the context of the long-term therapeutic use of cannabis-based medications, as well as in the context of public health and safety of cannabis use when performing day-to-day operations.
Cannabis is the most commonly used illicit drug in the world. However due to a changing legal landscape, and rising interest in therapeutic utility, there is an increasing trend in (long-term) use and possibly, cannabis impairment. Importantly, a growing body of evidence suggests regular cannabis users develop tolerance to the impairing, as well as the rewarding, effects of the drug. However, the neuroadaptations that may underlie cannabis tolerance remain unclear. Therefore, this double-blind, randomized, placebo controlled, cross-over study assessed the acute influence of cannabis on brain and behavioral outcomes in two distinct cannabis user groups. Twelve occasional (OUs) and 12 chronic (CUs) cannabis users received acute doses of cannabis (300 μg/kg THC) and placebo, and underwent ultra-high field functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS). In OUs, cannabis induced significant neurometabolic alterations in reward circuitry, namely decrements in functional connectivity and increments in striatal glutamate concentrations, which were associated with increases in subjective high and decreases in performance on a sustained attention task. Such changes were absent in CUs. The finding that cannabis altered circuitry and distorted behavior in OUs, but not CUs, suggests reduced responsiveness of the reward circuitry to cannabis intoxication in chronic users Taken together, the results suggest a pharmacodynamic mechanism for the development of tolerance to cannabis impairment.
Ecophysiological studies on Antarctic cryptophytes to assess whether climatic changes such as ocean acidification and enhanced stratification affect their growth in Antarctic coastal waters in the future are lacking so far. This is the first study that investigated the combined effects of increasing availability of pCO2 (400 and 1000 µatm) and irradiance (20, 200 and 500 μmol photons m−2 s −1) on growth, elemental composition and photophysiology of the Antarctic cryptophyte Geminigera cryophila. Under ambient pCO2, this species was characterized by a pronounced sensitivity to increasing irradiance with complete growth inhibition at the highest light intensity. Interestingly, when grown under high pCO2 this negative light effect vanished and it reached highest rates of growth and particulate organic carbon production at the highest irradiance compared to the other tested experimental conditions. Our results for G. cryophila reveal beneficial effects of ocean acidification in conjunction with enhanced irradiance on growth and photosynthesis. Hence, cryptophytes such as G. cryophila may be potential winners of climate change, potentially thriving better in more stratified and acidic coastal waters and contributing in higher abundance to future phytoplankton assemblages of coastal Antarctic waters.
Highlights
• The goal was to assess the intra- and inter-scanner reproducibility of qMRI data.
• Mean scan-rescan variations were not exceeding 2.14%.
• Mean inter-scanner model deviations were not exceeding 5.21%.
• Provided that identical acquisition sequences are used, discrepancies between qMRI data acquired with different scanner models are low.
Abstract
Background: Quantitative MRI (qMRI) techniques allow assessing cerebral tissue properties. However, previous studies on the accuracy of quantitative T1 and T2 mapping reported a scanner model bias of up to 10% for T1 and up to 23% for T2. Such differences would render multi-centre qMRI studies difficult and raise fundamental questions about the general precision of qMRI. A problem in previous studies was that different methods were used for qMRI parameter mapping or for measuring the transmitted radio frequency field B1 which is critical for qMRI techniques requiring corrections for B1 non-uniformities.
Aims: The goal was to assess the intra- and inter-scanner reproducibility of qMRI data at 3 T, using two different scanner models from the same vendor with exactly the same multiparametric acquisition protocol.
Methods: Proton density (PD), T1, T2* and T2 mapping was performed on healthy subjects and on a phantom, performing each measurement twice for each of two scanner models. Although the scanners had different hardware and software versions, identical imaging sequences were used for PD, T1 and T2* mapping, adapting the codes of an existing protocol on the older system line by line to match the software version of the newer scanner. For T2-mapping, the respective manufacturer’s sequence was used which depended on the software version. However, system-dependent corrections were carried out in this case. Reproducibility was assessed by average values in regions of interest.
Results: Mean scan-rescan variations were not exceeding 2.14%, with average values of 1.23% and 1.56% for the new and old system, respectively. Inter-scanner model deviations were not exceeding 5.21% with average values of about 2.2–3.8% for PD, 2.5–3.0% for T2*, 1.6–3.1% for T1 and 3.3–5.2% for T2.
Conclusions: Provided that identical acquisition sequences are used, discrepancies between qMRI data acquired with different scanner models are low. The level of systematic differences reported in this work may help to interpret multi-centre data.
Objective: Randomized trials have shown that concomitant methotrexate (MTX) augments the effectiveness of tumour necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA), but its benefit in psoriatic arthritis (PsA) has not been demonstrated. The goal of this study was to examine whether the impact of concomitant MTX on therapeutic outcomes in patients with PsA was similar to its effects in RA.
Methods: We used data from highly comparable and concurrent observational studies of patients with PsA (N = 1424) or RA (N = 3148) who initiated adalimumab therapy during routine clinical care. The 28-joint Disease Activity Score (DAS28) and patient-reported pain scores were evaluated in patients who received 24 months of continuous treatment with adalimumab monotherapy or adalimumab + MTX and in patients who initiated or stopped concomitant MTX during ongoing adalimumab therapy.
Results: Twenty-four months of continuous treatment with adalimumab + MTX was superior to adalimumab monotherapy in RA patients, while no significant difference was observed in patients with PsA. RA patients who added MTX during the study showed significant individual improvements in DAS28 and pain scores at 6 months after the change in therapy, while those who removed MTX had slight increases in disease activity. In contrast, in patients with PsA, neither initiation nor removal of MTX during continuous adalimumab therapy had a significant effect on therapeutic outcomes.
Conclusion: Addition of MTX to adalimumab confers further therapeutic benefit in patients with RA, but not in those with PsA, suggesting differences in MTX effects in these two patient populations.
Clinicaltrials.gov NCT01078090, NCT01077258, NCT01111240
We investigate the role of the Pauli Exclusion Principle (PEP) for light nuclei, at the examples of 12C and 16O. We show that ignoring the PEP does lead not only to a too dense spectrum at low energy but also to a wrong grouping into bands. Using a geometrical mapping, a triangular structure for 12C and a tetrahedral structure in 16O in the ground state is obtained by using the indistinguishably of the α-particles.
Based on the positive results of the 0.63 m unmodulated 325 MHz Ladder-RFQ prototype from 2013 to 2016 [1, 2], a modulated 3.3m Ladder-RFQ (s. Fig. 1) has been designed and built for the acceleration of up to 100 mA protons from 95 keV to 3.0 MeV at the FAIR p-Linac [3, 4]. In this paper, we will show the results of manufacturing as well as low level RF measurements of the Ladder-RFQ including flatness and frequency tuning.
Understanding the complexity of transcriptional regulation is a major goal of computational biology. Because experimental linkage of regulatory sites to genes is challenging, computational methods considering epigenomics data have been proposed to create tissue-specific regulatory maps. However, we showed that these approaches are not well suited to account for the variations of the regulatory landscape between cell-types. To overcome these drawbacks, we developed a new method called STITCHIT, that identifies and links putative regulatory sites to genes. Within STITCHIT, we consider the chromatin accessibility signal of all samples jointly to identify regions exhibiting a signal variation related to the expression of a distinct gene. STITCHIT outperforms previous approaches in various validation experiments and was used with a genome-wide CRISPR-Cas9 screen to prioritize novel doxorubicin-resistance genes and their associated non-coding regulatory regions. We believe that our work paves the way for a more refined understanding of transcriptional regulation at the gene-level.
In fungi, the mitochondrial respiratory chain complexes (complexes I–IV) are responsible for oxidative phosphorylation, as in higher eukaryotes. Cryo-EM was used to identify a 200 kDa membrane protein from Neurospora crassa in lipid nanodiscs as cytochrome c oxidase (complex IV) and its structure was determined at 5.5 Å resolution. The map closely resembles the cryo-EM structure of complex IV from Saccharomyces cerevisiae. Its ten subunits are conserved in S. cerevisiae and Bos taurus, but other transmembrane subunits are missing. The different structure of the Cox5a subunit is typical for fungal complex IV and may affect the interaction with complex III in a respiratory supercomplex. Additional density was found between the matrix domains of the Cox4 and Cox5a subunits that appears to be specific to N. crassa.
The small GTPases H, K, and NRAS are molecular switches that are indispensable for proper regulation of cellular proliferation and growth. Mutations in this family of proteins are associated with cancer and result in aberrant activation of signaling processes caused by a deregulated recruitment of downstream effector proteins. In this study, we engineered novel variants of the Ras-binding domain (RBD) of the kinase CRAF. These variants bound with high affinity to the effector binding site of active Ras. Structural characterization showed how the newly identified mutations cooperate to enhance affinity to the effector binding site compared to RBDwt. The engineered RBD variants closely mimic the interaction mode of naturally occurring Ras effectors and as dominant negative affinity reagent block their activation. Experiments with cancer cells showed that expression of these RBD variants inhibits Ras signaling leading to a reduced growth and inductions of apoptosis. Using the optimized RBD variants, we stratified patient-derived colorectal cancer organoids according to Ras dependency, which showed that the presence of Ras mutations was insufficient to predict sensitivity to Ras inhibition.
Attention-Deficit/Hyperactivity Disorder (ADHD) is frequently comorbid with other psychiatric disorders and also with somatic conditions, such as obesity. In addition to the clinical overlap, significant genetic correlations have been found between ADHD and obesity as well as body mass index (BMI). The biological mechanisms driving this association are largely unknown, but some candidate systems, like dopaminergic neurotransmission and circadian rhythm, have been suggested. Our aim was to identify the biological mechanisms underpinning the link between ADHD and obesity measures. Using the largest GWAS summary statistics currently available for ADHD (N=53,293), BMI (N=681,275), and obesity (N=98,697), we first tested the association of dopaminergic and circadian rhythm gene sets with each phenotype. This hypothesis-driven approach showed that the dopaminergic gene set was associated with both ADHD (P=5.81×10−3) and BMI (P=1.63×10−5), while the circadian rhythm gene set was associated with BMI only (P=1.28×10−3). We then took a data-driven approach by conducting genome-wide ADHD-BMI and ADHD-obesity gene-based meta-analyses, followed by pathway enrichment analyses. This approach further supported the implication of dopaminergic signaling in the link between ADHD and obesity measures, as the Dopamine-DARPP32 Feedback in cAMP Signaling pathway was significantly enriched in both the ADHD-BMI and ADHD-obesity gene-based meta-analysis results. Our findings suggest that dopaminergic neurotransmission, partially through DARPP-32-dependent signaling, is a key player underlying the genetic overlap between ADHD and obesity measures. Uncovering the shared etiological factors underlying the frequently observed ADHD-obesity comorbidity may have important implications in terms of preventive interventions and/or efficient treatment of these conditions.
Attention-Deficit/Hyperactivity Disorder (ADHD) and obesity are frequently comorbid, genetically correlated, and share brain substrates. The biological mechanisms driving this association are unclear, but candidate systems, like dopaminergic neurotransmission and circadian rhythm, have been suggested. Our aim was to identify the biological mechanisms underpinning the genetic link between ADHD and obesity measures and investigate associations of overlapping genes with brain volumes. We tested the association of dopaminergic and circadian rhythm gene sets with ADHD, body mass index (BMI), and obesity (using GWAS data of N=53,293, N=681,275, and N=98,697, respectively). We then conducted genome-wide ADHD-BMI and ADHD-obesity gene-based meta-analyses, followed by pathway enrichment analyses. Finally, we tested the association of ADHD-BMI overlapping genes with brain volumes (primary GWAS data N=10,720–10,928; replication data N=9,428). The dopaminergic gene set was associated with both ADHD (P=5.81×10−3) and BMI (P=1.63×10−5), the circadian rhythm was associated with BMI (P=1.28×10−3). The genome-wide approach also implicated the dopaminergic system, as the Dopamine-DARPP32 Feedback in cAMP Signaling pathway was enriched in both ADHD-BMI and ADHD-obesity results. The ADHD-BMI overlapping genes were associated with putamen volume (P=7.7×10−3; replication data P=3.9×10−2) – a brain region with volumetric reductions in ADHD and BMI and linked to inhibitory control. Our findings suggest that dopaminergic neurotransmission, partially through DARPP-32-dependent signaling and involving the putamen, is a key player underlying the genetic overlap between ADHD and obesity measures. Uncovering shared etiological factors underlying the frequently observed ADHD-obesity comorbidity may have important implications in terms of prevention and/or efficient treatment of these conditions.
Highlights
• This current review covers studies that have identified long non-coding RNAs in aortic aneurysm development and progression.
• We separately discuss transcripts and mechanisms of importance to thoracic as well as abdominal aortic aneurysms.
• Functional data on lncRNAs being identified are highlighted.
• Some have been studied in human as well as experimental models of the disease pathology.
Abstract
Aortic aneurysm (AA) is a complex and dangerous vascular disease, featuring progressive and irreversible vessel dilatation. AA is typically detected either by screening, or identified incidentally through imaging studies. To date, no effective pharmacological therapies have been identified for clinical AA management, and either endovascular repair or open surgery remains the only option capable of preventing aneurysm rupture. In recent years, multiple research groups have endeavored to both identify noncoding RNAs and to clarify their function in vascular diseases, including aneurysmal pathologies. Notably, the molecular roles of noncoding RNAs in AA development appear to vary significantly between thoracic aortic aneurysms (TAAs) and abdominal aortic aneurysms (AAAs). Some microRNAs (miRNA - a non-coding RNA subspecies) appear to contribute to AA pathophysiology, with some showing major potential for use as biomarkers or as therapeutic targets. Studies of long noncoding RNAs (lncRNAs) are more limited, and their specific contributions to disease development and progression largely remain unexplored. This review aims to summarize and discuss the most current data on lncRNAs and their mediation of AA pathophysiology.
Telemonitoring devices can be used to screen consumer characteristics and mitigate information asymmetries that lead to adverse selection in insurance markets. Nevertheless, some consumers value their privacy and dislike sharing private information with insurers. In a secondbest efficient Miyazaki-Wilson-Spence (MWS) framework, we allow consumers to reveal their risk type for an individual subjective cost and show analytically how this affects insurance market equilibria as well as social welfare. We find that information disclosure can substitute deductibles for consumers whose transparency aversion is sufficiently low. This can lead to a Pareto improvement of social welfare. Yet, if all consumers are offered cross-subsidizing contracts, the introduction of a screening contract decreases or even eliminates cross-subsidies. Given the prior existence of a cross-subsidizing MWS equilibrium, utility is shifted from individuals who do not reveal their private information to those who choose to reveal. Our analysis informs the discussion on consumer protection in the context of digitalization. It shows that new technologies challenge cross-subsidization in insurance markets, and it stresses the negative externalities that digitalization has on consumers who are unwilling to take part in this development.
This paper studies insurance demand for individuals with limited financial literacy. We propose uncertainty about insurance payouts, resulting from contract complexity, as a novel channel that affects decision-making of financially illiterate individuals. Then, a trade-off between second-order (risk aversion) and third-order (prudence) risk preferences drives insurance demand. Sufficiently prudent individuals raise insurance demand upon an increase in contract complexity, while the effect is reversed for less prudent individuals. We characterize competitive market equilibria that feature complex contracts since firms face costs to reduce complexity. Based on the equilibrium analysis, we propose a monetary measure for the welfare cost of financial illiteracy and show that it is mainly driven by individuals’ risk aversion. Finally, we discuss implications for regulation and consumer protection.
LICE is one of the four major LHC experiments at CERN. When the accelerator enters the Run 3 data-taking period, starting in 2021, ALICE expects almost 100 times more Pb-Pb central collisions than now, resulting in a large increase of data throughput. In order to cope with this new challenge, the collaboration had to extensively rethink the whole data processing chain, with a tighter integration between Online and Offline computing worlds. Such a system, code-named ALICE O2, is being developed in collaboration with the FAIR experiments at GSI. It is based on the ALFA framework which provides a generalized implementation of the ALICE High Level Trigger approach, designed around distributed software entities coordinating and communicating via message passing.
We will highlight our efforts to integrate ALFA within the ALICE O2 environment. We analyze the challenges arising from the different running environments for production and development, and conclude on requirements for a flexible and modular software framework. In particular we will present the ALICE O2 Data Processing Layer which deals with ALICE specific requirements in terms of Data Model. The main goal is to reduce the complexity of development of algorithms and managing a distributed system, and by that leading to a significant simplification for the large majority of the ALICE users.
The Kinase Chemogenomic Set (KCGS): An open science resource for kinase vulnerability identification
(2019)
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) is the most highly annotated set of selective kinase inhibitors available to researchers for use in cell-based screens.
This paper sheds light on the life insurance sector’s liquidity risk exposure. Life insurers are important long-term investors on financial markets. Due to their long-term investment horizon they cannot quickly adapt to changes in macroeconomic conditions. Rising interest rates in particular can expose life insurers to run-like situations, since a slow interest rate passthrough incentivizes policyholders to terminate insurance policies and invest the proceeds at relatively high market interest rates. We develop and empirically calibrate a granular model of policyholder behavior and life insurance cash flows to quantify insurers’ liquidity risk exposure stemming from policy terminations. Our model predicts that a sharp interest rate rise by 4.5pp within two years would force life insurers to liquidate 12% of their initial assets. While the associated fire sale costs are small under reasonable assumptions, policy terminations plausibly erase 30% of life insurers’ capital due to mark-to-market accounting. Our analysis reveals a mechanism by which monetary policy tightening increases liquidity risk exposure of non-bank financial intermediaries with long-term assets.
Background. Atherothrombotic disease, including coronary artery disease (CAD) and peripheral artery disease (PAD), can lead to cardiovascular (CV) events, such as myocardial infarction, stroke, limb ischemia, heart failure, and CV death. Aim. Evaluate the humanistic and economic burden of CAD and PAD and identify unmet needs through a comprehensive literature review. Methods. Relevant search terms were applied across online publication databases. Studies published between January 2010 and August 2017 meeting the inclusion/exclusion criteria were selected; guidelines were also included. Two rounds of screening were applied to select studies of relevance. Results. Worldwide data showed approximately 5–8% prevalence of CAD and 10–20% prevalence of PAD, dependent on the study design, average age, gender, and geographical location. Data from the REACH registry indicated that 18–35% of patients with CAD and 46–68% of patients with PAD had disease in one or more vascular beds. Use of medication to control modifiable CV risk factors was variable by country (lower in France than in Canada); statins and aspirin were the most widely used therapies in patients with chronic disease. Survival rates have improved with medical advancements, but there is an additional need to improve the humanistic burden of disease (i.e., associated disability and quality of life). The economic burden of atherothrombotic disease is high and expected to increase with increased survival and the aging population. Conclusion. CAD and PAD represent a substantial humanistic and economic burden worldwide, highlighting a need for new interventions to reduce the incidence of atherothrombotic disease.
Highlights
• Subcrustal earthquakes detected beneath Fogo volcano, Cape Verde.
• At the focal depth of 40 km temperatures are likely too high for brittle failure.
• The earthquakes may originate from magma injection into a deep subcrustal reservoir.
• This observation indicates a distinct magma supply system of Fogo volcano.
Abstract
Fogo volcano belongs to the Cape Verde hotspot and its most recent eruption occurred from November 2014 to February 2015. From January to December 2016 we operated a temporary seismic network and array on Fogo and were able to locate 289 earthquakes in total. Array analysis shows that most of the events occur within the crust at distances >25 km near the neighboring island of Brava. However, on 15th August 2016 the network recorded an isolated cluster of >20 earthquakes, 13 of which could be located beneath the southern part of Fogo. The differences between S- and P-wave arrival times at steep incidence clearly indicate focal depths between approximately 38 and 44 km whereas receiver-function analyses place the Moho discontinuity at depths between 11 and 14 km. Thus, the earthquakes are located well within the upper mantle directly beneath Fogo. In view of the elevated upper-mantle temperatures within a hotspot regime, we propose that fracturing induced by magmatic injection is the most likely cause for the observed deep earthquakes.
The current problem of increasing antibiotic resistance and the resurgence of numerous infections indicate the need for novel vaccination strategies more than ever. In vaccine development, the search for and the selection of adequate vaccine antigens is the first important step. In recent years, bacterial outer membrane proteins have become of major interest, as they are the main proteins interacting with the extracellular environment. Trimeric autotransporter adhesins (TAAs) are important virulence factors in many Gram-negative bacteria, are localised on the bacterial surface, and mediate the first adherence to host cells in the course of infection. One example is the Neisseria adhesin A (NadA), which is currently used as a subunit in a licensed vaccine against Neisseria meningitidis. Other TAAs that seem promising vaccine candidates are the Acinetobacter trimeric autotransporter (Ata), the Haemophilus influenzae adhesin (Hia), and TAAs of the genus Bartonella. Here, we review the suitability of various TAAs as vaccine candidates.
The capacity of pathogenic microorganisms to adhere to host cells and avoid clearance by the host immune system is the initial and most decisive step leading to infections. Bacteria have developed different strategies to attach to diverse host surface structures. One important strategy is the adhesion to extracellular matrix (ECM) proteins (e.g., collagen, fibronectin, laminin) that are highly abundant in connective tissue and basement membranes. Gram-negative bacteria express variable outer membrane proteins (adhesins) to attach to the host and to initiate the process of infection. Understanding the underlying molecular mechanisms of bacterial adhesion is a prerequisite for targeting this interaction by “anti-ligands” to prevent colonization or infection of the host. Future development of such “anti-ligands” (specifically interfering with bacteria-host matrix interactions) might result in the development of a new class of anti-infective drugs for the therapy of infections caused by multidrug-resistant Gram-negative bacteria. This review summarizes our current knowledge about the manifold interactions of adhesins expressed by Gram-negative bacteria with ECM proteins and the use of this information for the generation of novel therapeutic antivirulence strategies.
Gradient-consistent enrichment of finite element spaces for the DNS of fluid-particle interaction
(2019)
Highlights
• Monolithic scheme for particulate flows preventing an oscillating pressure along the interface.
• The choice of enriching shape functions is driven by the properties of its gradient instead of its value.
• The choice of enriching shape functions inherits a natural stabilization on small cut elements.
Abstract
We present gradient-consistent enriched finite element spaces for the simulation of free particles in a fluid. This involves forces being exchanged between the particles and the fluid at the interface. In an earlier work [23] we derived a monolithic scheme which includes the interaction forces into the Navier-Stokes equations by means of a fictitious domain like strategy. Due to an inexact approximation of the interface oscillations of the pressure along the interface were observed. In multiphase flows oscillations and spurious velocities are a common issue. The surface force term yields a jump in the pressure and therefore the oscillations are usually resolved by extending the spaces on cut elements in order to resolve the discontinuity. For the construction of the enriched spaces proposed in this paper we exploit the Petrov-Galerkin formulation of the vertex-centered finite volume method (PG-FVM), as already investigated in [23]. From the perspective of the finite volume scheme we argue that wrong discrete normal directions at the interface are the origin of the oscillations. The new perspective of normal vectors suggests to look at gradients rather than values of the enriching shape functions. The crucial parameter of the enrichment functions therefore is the gradient of the shape functions and especially the one of the test space. The distinguishing feature of our construction therefore is an enrichment that is based on the choice of shape functions with consistent gradients. These derivations finally yield a fitted scheme for the immersed interface. We further propose a strategy ensuring a well-conditioned system independent of the location of the interface. The enriched spaces can be used within any existing finite element discretization for the Navier-Stokes equation. Our numerical tests were conducted using the PG-FVM. We demonstrate that the enriched spaces are able to eliminate the oscillations.
Rotational test spaces for a fully-implicit FVM and FEM for the DNS of fluid-particle interaction
(2019)
The paper presents a fully-implicit and stable finite element and finite volume scheme for the simulation of freely moving particles in a fluid. The developed method is based on the Petrov-Galerkin formulation of a vertex-centered finite volume method (PG-FVM) on unstructured grids. Appropriate extension of the ansatz and test spaces lead to a formulation comparable to a fictitious domain formulation. The purpose of this work is to introduce a new concept of numerical modeling reducing the mathematical overhead which many other methods require. It exploits the identification of the PG-FVM with a corresponding finite element bilinear form. The surface integrals of the finite volume scheme enable a natural incorporation of the interface forces purely based on the original bilinear operator for the fluid. As a result, there is no need to expand the system of equations to a saddle-point problem. Like for fictitious domain methods the extended scheme treats the particles as rigid parts of the fluid. The distinguishing feature compared to most existing fictitious domain methods is that there is no need for an additional Lagrange multiplier or other artificial external forces for the fluid-solid coupling. Consequently, only one single solve for the derived linear system for the fluid together with the particles is necessary and the proposed method does not require any fractional time stepping scheme to balance the interaction forces between fluid and particles. For the linear Stokes problem we will prove the stability of both schemes. Moreover, for the stationary case the conservation of mass and momentum is not violated by the extended scheme, i.e. conservativity is accomplished within the range of the underlying, unconstrained discretization scheme. The scheme is applicable for problems in two and three dimensions.
We explore the phase structure of the 1+1 dimensional Gross-Neveu model at finite number of fermion flavors using lattice field theory. Besides a chirally symmetric phase and a homogeneously broken phase we find evidence for the existence of an inhomogeneous phase, where the condensate is a spatially oscillating function. Our numerical results include a crude μ-T phase diagram.
Critical spin liquid versus valence-bond glass in a triangular-lattice organic antiferromagnet
(2019)
In the quest for materials with unconventional quantum phases, the organic triangular-lattice antiferromagnet κ-(ET)2Cu2(CN)3 has been extensively discussed as a quantum spin liquid (QSL) candidate. The description of its low temperature properties has become, however, a particularly challenging task. Recently, an intriguing quantum critical behaviour was suggested from low-temperature magnetic torque experiments. Here we highlight significant deviations of the experimental observations from a quantum critical scenario by performing a microscopic analysis of all anisotropic contributions, including Dzyaloshinskii–Moriya and multi-spin scalar chiral interactions. Instead, we show that disorder-induced spin defects provide a comprehensive explanation of the low-temperature properties. These spins are attributed to valence bond defects that emerge spontaneously as the QSL enters a valence-bond glass phase at low temperature. This theoretical treatment is applicable to a general class of frustrated magnetic systems and has important implications for the interpretation of magnetic torque, nuclear magnetic resonance, thermal transport and thermodynamic experiments.
Das Zusammenleben von Juden und Christen war in vielen deutschen Territorien, insbesondere in ländlichen Gebieten, viel enger, als man dies heute zumeist annimmt. Dafür finden sich auch in der Landgrafschaft Hessen-Kassel zahlreiche Belege. Hier soll das kirchliche Verwaltungsschrifttum zum Sprechen gebracht werden, das in Zusammenhang mit den Kasseler Superintendenten Paul Stein und Theophil Neuberger sowie dem Eschweger Superintendenten Johannes Hütterodt steht. Als Ausgangspunkt dienen insbesondere ihre Diensttagebücher.
The production of the Λ(1520) baryonic resonance has been measured at midrapidity in inelastic pp collisions at s√ = 7 TeV and in p-Pb collisions at sNN−−−√ = 5.02 TeV for non-single diffractive events and in multiplicity classes. The resonance is reconstructed through its hadronic decay channel Λ(1520) → pK− and the charge conjugate with the ALICE detector. The integrated yields and mean transverse momenta are calculated from the measured transverse momentum distributions in pp and p-Pb collisions. The mean transverse momenta follow mass ordering as previously observed for other hyperons in the same collision systems. A Blast-Wave function constrained by other light hadrons (π, K, K0S, p, Λ) describes the shape of the Λ(1520) transverse momentum distribution up to 3.5 GeV/c in p-Pb collisions. In the framework of this model, this observation suggests that the Λ(1520) resonance participates in the same collective radial flow as other light hadrons. The ratio of the yield of Λ(1520) to the yield of the ground state particle Λ remains constant as a function of charged-particle multiplicity, suggesting that there is no net effect of the hadronic phase in p-Pb collisions on the Λ(1520) yield.
Measurement of the inclusive J/ψ polarization at forward rapidity in pp collisions at √s = 8 TeV
(2019)
We report on the measurement of the inclusive J/ψ polarization parameters in pp collisions at a center of mass energy s√=8 TeV with the ALICE detector at the LHC. The analysis is based on a data sample corresponding to an integrated luminosity of 1.23 pb−1. J/ψ resonances are reconstructed in their di-muon decay channel in the rapidity interval 2.5<y<4.0 and over the transverse-momentum interval 2<pT<15 GeV/c. The three polarization parameters (λθ, λφ, λθφ) are measured as a function of pT both in the helicity and Collins-Soper reference frames. The measured J/ψ polarization parameters are found to be compatible with zero within uncertainties, contrary to expectations from all available predictions. The results are compared with the measurement in pp collisions at s√=7 TeV.
ϕ meson measurements provide insight into strangeness production, which is one of the key observables for the hot medium formed in high-energy heavy-ion collisions. ALICE measured ϕ production through its decay in muon pairs in Pb-Pb collisions at sNN−−−√ = 2.76 TeV in the intermediate transverse momentum range 2<pT<5 GeV/c and in the rapidity interval 2.5<y<4. The ϕ yield was measured as a function of the transverse momentum and collision centrality. The nuclear modification factor was obtained as a function of the average number of participating nucleons. Results were compared with the ones obtained via the kaon decay channel in the same pT range at midrapidity. The values of the nuclear modification factor in the two rapidity regions are in agreement within uncertainties.
The elliptic (v2), triangular (v3), and quadrangular (v4) flow coefficients of π±, K±, p+p¯¯¯, Λ+Λ¯¯¯¯, K0S, and the ϕ-meson are measured in Pb-Pb collisions at sNN−−−√=5.02 TeV. Results obtained with the scalar product method are reported for the rapidity range |y|< 0.5 as a function of transverse momentum, pT, at different collision centrality intervals between 0-70%, including ultra-central (0-1%) collisions for π±, K±, and p+p¯¯¯. For pT<3 GeV/c, the flow coefficients exhibit a particle mass dependence. At intermediate transverse momenta (3<pT<~8-10 GeV/c), particles show an approximate grouping according to their type (i.e., mesons and baryons). The ϕ-meson v2, which tests both particle mass dependence and type scaling, follows p+p¯¯¯ v2 at low pT and π± v2 at intermediate pT. The evolution of the shape of vn(pT) as a function of centrality and harmonic number n is studied for the various particle species. Flow coefficients of π±, K±, and p+p¯¯¯ for pT<3 GeV/c are compared to iEBE-VISHNU and MUSIC hydrodynamical calculations coupled to a hadronic cascade model (UrQMD). The iEBE-VISHNU calculations describe the results fairly well for pT<2.5 GeV/c, while MUSIC calculations reproduce the measurements for pT<1 GeV/c. A comparison to vn coefficients measured in Pb-Pb collisions at sNN−−−√ = 2.76 TeV is also provided.
Measurements of anisotropic flow coefficients with two- and multi-particle cumulants for inclusive charged particles in Pb-Pb collisions at sNN−−−√=5.02 and 2.76 TeV are reported in the pseudorapidity range |η|<0.8 and transverse momentum 0.2<pT<50 GeV/c. The full data sample collected by the ALICE detector in 2015 (2010), corresponding to an integrated luminosity of 12.7 (2.0) μb−1 in the centrality range 0-80%, is analysed. Flow coefficients up to the sixth flow harmonic (v6) are reported and a detailed comparison among results at the two energies is carried out. The pT dependence of anisotropic flow coefficients and its evolution with respect to centrality and harmonic number n are investigated. An approximate power-law scaling of the form vn(pT)∼pn/3T is observed for all flow harmonics at low pT (0.2<pT<3 GeV/c). At the same time, the ratios vn/vn/mm are observed to be essentially independent of pT for most centralities up to about pT=10 GeV/c. Analysing the differences among higher-order cumulants of elliptic flow (v2), which have different sensitivities to flow fluctuations, a measurement of the standardised skewness of the event-by-event v2 distribution P(v2) is reported and constraints on its higher moments are provided. The Elliptic Power distribution is used to parametrise P(v2), extracting its parameters from fits to cumulants. The measurements are compared to different model predictions in order to discriminate among initial-state models and to constrain the temperature dependence of the shear viscosity to entropy-density ratio.
Over the last decade, cases of metabolic syndrome and type II diabetes have increased exponentially. Exercise and ω-3 polyunsaturated fatty acid (PUFA)-enriched diets are usually prescribed but no therapy is effectively able to restore the impaired glucose metabolism, hypertension, and atherogenic dyslipidemia encountered by diabetic patients. PUFAs are metabolized by different enzymes into bioactive metabolites with anti- or pro-inflammatory activity. One important class of PUFA metabolizing enzymes are the cytochrome P450 (CYP) enzymes that can generate a series of bioactive products, many of which have been attributed protective/anti-inflammatory and insulin-sensitizing effects in animal models. PUFA epoxides are, however, further metabolized by the soluble epoxide hydrolase (sEH) to fatty acid diols. The biological actions of the latter are less well understood but while low concentrations may be biologically important, higher concentrations of diols derived from linoleic acid and docosahexaenoic acid have been linked with inflammation. One potential application for sEH inhibitors is in the treatment of diabetic retinopathy where sEH expression and activity is elevated as are levels of a diol of docosahexaenoic acid that can induce the destabilization of the retina vasculature.
Much of the research on Na+/H+ exchange has been done in prokaryotic models, mainly on the NhaA Na+/H+-exchanger from Escherichia coli (EcNhaA). Two conserved aspartate residues, Asp-163 and Asp-164, are essential for transport and are candidates for possible binding sites for the two H+ that are exchanged for one Na+ to make the overall transport process electrogenic. More recently, a proposed mechanism of transport for EcNhaA has suggested direct binding of one of the transported H+ to the conserved Lys-300 residue, a salt bridge partner of Asp-163. This contention is supported by a study reporting that substitution of the equivalent residue, Lys-305, of a related Na+/H+ antiporter, NapA from Thermus thermophilus, renders the transporter electroneutral. In this work, we sought to establish whether the Lys-300 residue and its partner Asp-163 are essential for the electrogenicity of EcNhaA. To that end, we replaced Lys-300 with Gln, either alone or together with the simultaneous substitution of Asp-163 with Asn, and characterized these transporter variants in electrophysiological experiments combined with H+ transport measurements and stability analysis. We found that K300Q EcNhaA can still support electrogenic Na+/H+ antiport in EcNhaA, but has reduced thermal stability. A parallel electrophysiological investigation of the K305Q variant of TtNapA revealed that it is also electrogenic. Furthermore, replacement of both salt bridge partners in the ion-binding site of EcNhaA produced an electrogenic variant (D163N/K300Q). Our findings indicate that alternative mechanisms sustain EcNhaA activity in the absence of canonical ion-binding residues and that the conserved lysines confer structural stability.