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Cross sections of the process 𝑒+𝑒−→𝜋0𝜋0𝐽/𝜓 at center-of-mass energies between 3.808 and 4.600 GeV are measured with high precision by using 12.4 fb−1 of data samples collected with the BESIII detector operating at the BEPCII collider facility. A fit to the measured energy-dependent cross sections confirms the existence of the charmoniumlike state 𝑌(4220). The mass and width of the 𝑌(4220) are determined to be (4220.4±2.4±2.3) MeV/𝑐2 and (46.2±4.7±2.1) MeV, respectively, where the first uncertainties are statistical and the second systematic. The mass and width are consistent with those measured in the process 𝑒+𝑒−→𝜋+𝜋−𝐽/𝜓. The neutral charmonium-like state 𝑍𝑐(3900)0 is observed prominently in the 𝜋0𝐽/𝜓 invariant-mass spectrum, and, for the first time, an amplitude analysis is performed to study its properties. The spin-parity of 𝑍𝑐(3900)0 is determined to be 𝐽𝑃=1+, and the pole position is (3893.1±2.2±3.0)−𝑖(22.2±2.6±7.0) MeV/𝑐2, which is consistent with previous studies of electrically charged 𝑍𝑐(3900)±. In addition, cross sections of 𝑒+𝑒− → 𝜋0𝑍𝑐(3900)0 → 𝜋0𝜋0𝐽/𝜓 are extracted, and the corresponding line shape is found to agree with that of the 𝑌(4220).
We report an amplitude analysis and branching fraction measurement of D+s→K+K−π+ decay using a data sample of 3.19 fb−1 recorded with BESIII detector at a center-of-mass energy of 4.178 GeV.
We perform a model-independent partial wave analysis in the low K+K− mass region to determine the K+K− S-wave lineshape, followed by an amplitude analysis of our very pure high-statistics sample.
The amplitude analysis provides an accurate determination of the detection efficiency allowing us to measure the branching fraction B(D+s→K+K−π+)=(5.47±0.08stat±0.13sys)%.
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−.
As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer. Within chronic lymphocytic leukemia (CLL), responses to 62% of drugs were associated with 2 or more mutations, and linked the B cell receptor (BCR) pathway to trisomy 12, an important driver of CLL. Based on drug responses, the disease could be organized into phenotypic subgroups characterized by exploitable dependencies on BCR, mTOR, or MEK signaling and associated with mutations, gene expression, and DNA methylation. Fourteen percent of CLLs were driven by mTOR signaling in a non–BCR-dependent manner. Multivariate modeling revealed immunoglobulin heavy chain variable gene (IGHV) mutation status and trisomy 12 as the most important modulators of response to kinase inhibitors in CLL. Ex vivo drug responses were associated with outcome. This study overcomes the perception that most mutations do not influence drug response of cancer, and points to an updated approach to understanding tumor biology, with implications for biomarker discovery and cancer care.
The Born cross sections of the e+e− → +¯ − and e+e− → −¯ + processes are determined for centerof-mass energy from 2.3864 to 3.0200 GeV with the BESIII detector. The cross section lineshapes can be described properly by a pQCD function and the resulting ratio of effective form factors for the + and − is consistent with 3. In addition, ratios of the + electric and magnetic form factors, |GE /GM |, are obtained at three center-of-mass energies through an analysis of the angular distributions. These measurements, which are studied for the first time in the off-resonance region, provide precision experimental input for understanding baryonic structure. The observed new features of the ± form factors require more theoretical discussions for the hyperons.
Using 5.9 pb−1 of e+e− annihilation data collected at center-of-mass energies from 3.640 to 3.701 GeV with the BESIII detector at the BEPCII Collider, we measure the observed cross sections of e+e−→K0SX (where X=anything). From a fit to these observed cross sections with the sum of continuum and ψ(3686) and J/ψ Breit-Wigner functions and considering initial state radiation and the BEPCII beam energy spread, we obtain for the first time the inclusive decay branching fraction B(ψ(3686)→K0SX)=(16.04±0.29±0.90)%, where the first uncertainty is statistical and the second is systematic.
Using 2.93 fb−1 of 𝑒+𝑒− collision data taken at a center-of-mass energy of 3.773 GeV by the BESIII detector at the BEPCII, we measure the branching fractions of the singly Cabibbo-suppressed decays 𝐷→𝜔𝜋𝜋 to be ℬ(𝐷0→𝜔𝜋+𝜋−)=(1.33±0.16±0.12)×10−3 and ℬ(𝐷+→𝜔𝜋+𝜋0)=(3.87±0.83±0.25)×10−3, where the first uncertainties are statistical and the second ones systematic. The statistical significances are 12.9𝜎 and 7.7𝜎, respectively. The precision of ℬ(𝐷0→𝜔𝜋+𝜋−) is improved by a factor of 2.1 over prior measurements, and ℬ(𝐷+→𝜔𝜋+𝜋0) is measured for the first time. No significant signal for 𝐷0→𝜔𝜋0𝜋0 is observed, and the upper limit on the branching fraction is ℬ(𝐷0→𝜔𝜋0𝜋0)<1.10×10−3 at the 90% confidence level. The branching fractions of 𝐷→𝜂𝜋𝜋 are also measured and consistent with existing results.
Using 2.93 fb−1 of 𝑒+𝑒− collision data taken at a center-of-mass energy of 3.773 GeV with the BESIII detector, we report the first measurements of the absolute branching fractions of 14 hadronic 𝐷0(+) decays to exclusive final states with an 𝜂, e.g., 𝐷0→𝐾−𝜋+𝜂, 𝐾0𝑆𝜋0𝜂, 𝐾+𝐾−𝜂, 𝐾0𝑆𝐾0𝑆𝜂, 𝐾−𝜋+𝜋0𝜂, 𝐾0𝑆𝜋+𝜋−𝜂, 𝐾0𝑆𝜋0𝜋0𝜂, and 𝜋+𝜋−𝜋0𝜂; 𝐷+→𝐾0𝑆𝜋+𝜂, 𝐾0𝑆𝐾+𝜂, 𝐾−𝜋+𝜋+𝜂, 𝐾0𝑆𝜋+𝜋0𝜂, 𝜋+𝜋+𝜋−𝜂, and 𝜋+𝜋0𝜋0𝜂. Among these decays, the 𝐷0→𝐾−𝜋+𝜂 and 𝐷+→𝐾0 𝑆𝜋+𝜂 decays have the largest branching fractions, which are ℬ(𝐷0→𝐾−𝜋+𝜂) = (1.853±0.025stat±0.031syst)% and ℬ(𝐷+→𝐾0𝑆𝜋+𝜂) = (1.309±0.037stat±0.031syst)%, respectively. The charge-parity asymmetries for the six decays with highest event yields are determined, and no statistically significant charge-parity violation is found.
Background: Patients with chronic kidney disease (CKD) are at high risk of myocardial infarction. Cardiac troponins are the biomarkers of choice for the diagnosis of acute myocardial infarction (AMI) without ST‐segment elevation (NSTE). In patients with CKD, troponin levels are often chronically elevated, which reduces their diagnostic utility when NSTE‐AMI is suspected. The aim of this study was to derive a diagnostic algorithm for serial troponin measurements in patients with CKD and suspected NSTE‐AMI.
Methods and Results: Two cohorts, 1494 patients from a prospective cohort study with high‐sensitivity troponin I (hs‐cTnI) measurements and 7059 cases from a clinical registry with high‐sensitivity troponin T (hs‐cTnT ) measurements, were analyzed. The prospective cohort comprised 280 CKD patients (estimated glomerular filtration rate <60 mL/min/1.73 m2). The registry data set contained 1581 CKD patients. In both cohorts, CKD patients were more likely to have adjudicated NSTE‐AMI than non‐CKD patients. The specificities of hs‐cTnI and hs‐cTnT to detect NSTE‐AMI were reduced with CKD (0.82 versus 0.91 for hs‐cTnI and 0.26 versus 0.73 for hs‐cTnT) but could be restored by applying optimized cutoffs to either the first or a second measurement after 3 hours. The best diagnostic performance was achieved with an algorithm that incorporates serial measurements and rules in or out AMI in 69% (hs‐cTnI) and 55% (hs‐cTnT) of CKD patients.
Conclusions: The diagnostic performance of high‐sensitivity cardiac troponins in patients with CKD with suspected NSTE‐AMI is improved by use of an algorithm based on admission troponin and dynamic changes in troponin concentration.
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.
Using 2.93 fb−1 of 𝑒+𝑒− annihilation data collected at a center-of-mass energy √𝑠=3.773 GeV with the BESIII detector operating at the BEPCII collider, we search for the semileptonic 𝐷0(+) decays into a 𝑏1(1235)−(0) axial-vector meson for the first time. No significant signal is observed for either charge combination. The upper limits on the product branching fractions are ℬ𝐷0→𝑏1(1235)−𝑒+𝜈𝑒·ℬ𝑏1(1235) −→ 𝜔𝜋−<1.12×10−4 and ℬ𝐷+→𝑏1(1235)0𝑒+𝜈𝑒·ℬ𝑏1(1235)0→𝜔𝜋0<1.75×10−4 at the 90% confidence level.
Experiment NA49 at the Cern SPS uses a large acceptance detector for a systematic study of particle yields and correlations in nucleus-nucleus, nucleon-nucleus and nucleon-nucleon collisions. Preliminary results for Pb+Pb collisions at 40, 80 and 158 A*GeV beam energy are shown and compared to measurements at lower and higher energies.
Background & Aims: Hepatitis C virus (HCV) cell entry is mediated by several cell surface receptors, including scavenger receptor class B type I (SR-BI). Oxidized low density lipoprotein (oxLDL) inhibits the interaction between HCV and SR-BI in a noncompetitive manner. We tested whether serum oxLDL levels correlate with sustained virologic response (SVR) rates after interferon-based treatment of chronic hepatitis C.
Methods: Baseline oxLDL was determined in 379 participants with chronic HCV genotype 1 infection from the INDIV-2 study using a commercial enzyme-linked immunosorbent assay. The mechanistic in vitro studies used full-length and subgenomic HCV genomes replicating in hepatoma cells.
Results: In the multivariate analysis, oxLDL was found to be an independent predictor of SVR. Oxidized LDL did not correlate with markers of inflammation (alanine transaminase, ferritin), nor was serum oxLDL affected by exogenous interferon administration. Also, oxLDL did not alter the sensitivity of HCV replication to interferon. However, oxLDL was found to be a potent inhibitor of cell-to-cell spread of HCV between adjacent cells in vitro. It could thus reduce the rate at which new cells are infected by HCV through either the cell-free or cell-to-cell route. Finally, serum oxLDL was significantly associated with the estimated infected cell loss rate under treatment.
Conclusions: Oxidized LDL is a novel predictor of SVR after interferon-based therapy and may explain the previously observed association of LDL with SVR. Rather than being a marker of activated antiviral defenses it may improve chances of SVR by limiting spread of infection to naive cells through the cell-to-cell route.
Background: Tuberous sclerosis complex (TSC), a multisystem genetic disorder, affects many organs and systems, characterized by benign growths. This German multicenter study estimated the disease-specific costs and cost-driving factors associated with various organ manifestations in TSC patients. Methods: A validated, three-month, retrospective questionnaire was administered to assess the sociodemographic and clinical characteristics, organ manifestations, direct, indirect, out-of-pocket, and nursing care-level costs, completed by caregivers of patients with TSC throughout Germany. Results: The caregivers of 184 patients (mean age 9.8 ± 5.3 years, range 0.7–21.8 years) submitted questionnaires. The reported TSC disease manifestations included epilepsy (92%), skin disorders (86%), structural brain disorders (83%), heart and circulatory system disorders (67%), kidney and urinary tract disorders (53%), and psychiatric disorders (51%). Genetic variations in TSC2 were reported in 46% of patients, whereas 14% were reported in TSC1. Mean total direct health care costs were EUR 4949 [95% confidence interval (95% CI) EUR 4088–5863, median EUR 2062] per patient over three months. Medication costs represented the largest direct cost category (54% of total direct costs, mean EUR 2658), with mechanistic target of rapamycin (mTOR) inhibitors representing the largest share (47%, EUR 2309). The cost of anti-seizure drugs (ASDs) accounted for a mean of only EUR 260 (5%). Inpatient costs (21%, EUR 1027) and ancillary therapy costs (8%, EUR 407) were also important direct cost components. The mean nursing care-level costs were EUR 1163 (95% CI EUR 1027–1314, median EUR 1635) over three months. Total indirect costs totaled a mean of EUR 2813 (95% CI EUR 2221–3394, median EUR 215) for mothers and EUR 372 (95% CI EUR 193–586, median EUR 0) for fathers. Multiple regression analyses revealed polytherapy with two or more ASDs and the use of mTOR inhibitors as independent cost-driving factors of total direct costs. Disability and psychiatric disease were independent cost-driving factors for total indirect costs as well as for nursing care-level costs. Conclusions: This study revealed substantial direct (including medication), nursing care-level, and indirect costs associated with TSC over three months, highlighting the spectrum of organ manifestations and their treatment needs in the German healthcare setting.
Stored and cooled highly-charged ions offer unprecedented capabilities for precision studies in realm of atomic-, nuclear-structure and astrophysics. In context of the latter, after the successful investigation of the cross section of 96Ru(p,γ) in 2009, in 2016 the first measurement of the 124Xe(p,γ)125Cs reaction was performed at the Experimental Storage Ring (ESR) at GSI.
The purpose of this phase III clinical trial was to compare two different extracellular contrast agents, 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine, for magnetic resonance imaging (MRI) in patients with known or suspected focal renal lesions. Using a multicenter, single-blind, interindividual, randomized study design, both contrast agents were compared in a total of 471 patients regarding their diagnostic accuracy, sensitivity, and specificity to correctly classify focal lesions of the kidney. To test for noninferiority the diagnostic accuracy rates for both contrast agents were compared with CT results based on a blinded reading. The average diagnostic accuracy across the three blinded readers (‘average reader’) was 83.7% for gadobutrol and 87.3% for gadopentate dimeglumine. The increase in accuracy from precontrast to combined precontrast and postcontrast MRI was 8.0% for gadobutrol and 6.9% for gadopentate dimeglumine. Sensitivity of the average reader was 85.2% for gadobutrol and 88.7% for gadopentate dimeglumine. Specificity of the average reader was 82.1% for gadobutrol and 86.1% for gadopentate dimeglumine. In conclusion, this study documents evidence for the noninferiority of a single i.v. bolus injection of 1.0 M gadobutrol compared with 0.5 M gadopentate dimeglumine in the diagnostic assessment of renal lesions with CE-MRI.
Abrasion-ablation models and the empirical EPAX parametrization of projectile fragmentation are described. Their cross section predictions are compared to recent data of the fragmentation of secondary beams of neutron-rich, unstable 19,20,21O isotopes at beam energies near 600 MeV/nucleon as well as data for stable 17,18O beams.
HIF1A reduces acute lung injury by optimizing carbohydrate metabolism in the alveolar epithelium
(2013)
Background: While acute lung injury (ALI) contributes significantly to critical illness, it resolves spontaneously in many instances. The majority of patients experiencing ALI require mechanical ventilation. Therefore, we hypothesized that mechanical ventilation and concomitant stretch-exposure of pulmonary epithelia could activate endogenous pathways important in lung protection.
Methods and Findings: To examine transcriptional responses during ALI, we exposed pulmonary epithelia to cyclic mechanical stretch conditions—an in vitro model resembling mechanical ventilation. A genome-wide screen revealed a transcriptional response similar to hypoxia signaling. Surprisingly, we found that stabilization of hypoxia-inducible factor 1A (HIF1A) during stretch conditions in vitro or during ventilator-induced ALI in vivo occurs under normoxic conditions. Extension of these findings identified a functional role for stretch-induced inhibition of succinate dehydrogenase (SDH) in mediating normoxic HIF1A stabilization, concomitant increases in glycolytic capacity, and improved tricarboxylic acid (TCA) cycle function. Pharmacologic studies with HIF activator or inhibitor treatment implicated HIF1A-stabilization in attenuating pulmonary edema and lung inflammation during ALI in vivo. Systematic deletion of HIF1A in the lungs, endothelia, myeloid cells, or pulmonary epithelia linked these findings to alveolar-epithelial HIF1A. In vivo analysis of 13C-glucose metabolites utilizing liquid-chromatography tandem mass-spectrometry demonstrated that increases in glycolytic capacity, improvement of mitochondrial respiration, and concomitant attenuation of lung inflammation during ALI were specific for alveolar-epithelial expressed HIF1A.
Conclusions: These studies reveal a surprising role for HIF1A in lung protection during ALI, where normoxic HIF1A stabilization and HIF-dependent control of alveolar-epithelial glucose metabolism function as an endogenous feedback loop to dampen lung inflammation.
New experimental data for dissociation of relativistic 17Ne projectiles incident on targets of lead, carbon, and polyethylene targets at GSI are presented. Special attention is paid to the excitation and decay of narrow resonant states in 17Ne. Distributions of internal energy in the three-body system have been determined together with angular and partial-energy correlations between the decay products in different energy regions. The analysis was done using existing experimental data on 17Ne and its mirror nucleus 17N. The isobaric multiplet mass equation is used for assignment of observed resonances and their spins and parities. A combination of data from the heavy and light targets yielded cross sections and transition probabilities for the Coulomb excitations of the narrow resonant states. The resulting transition probabilities provide information relevant for a better understanding of the 17Ne structure.
Stored and cooled, highly-charged ions offer unprecedented capabilities for precision studies in the realm of atomic, nuclear structure and astrophysics[1]. After the successful investigation of the 96Ru(p,7)97Rh reaction cross section in 2009[2], the first measurement of the 124Xe(p,7)125Cs reaction cross section has been performed with decelerated, fully-ionized 124Xe ions in 2016 at the Experimental Storage Ring (ESR) of GSI[3]. Using a Double Sided Silicon Strip Detector, introduced directly into the ultra-high vacuum environment of a storage ring, the 125Cs proton-capture products have been successfully detected. The cross section has been measured at 5 different energies between 5.5AMeV and 8AMeV, on the high energy tail of the Gamow-window for hot, explosive scenarios such as supernovae and X-ray binaries. The elastic scattering on the H2 gas jet target is the major source of background to count the (p,7) events. Monte Carlo simulations show that an additional slit system in the ESR in combination with the energy information of the Si detector will enable background free measurements of the proton-capture products. The corresponding hardware is being prepared and will increase the sensitivity of the method tremendously.