The production of a $W$ boson in association with a single charm quark is studied using 140 fb–1 of $\sqrt{s}$ = $13$ $\mathrm{TeV}$ proton-proton collision data collected with the ATLAS detector at ...the Large Hadron Collider. The charm quark is tagged by the presence of a charmed hadron reconstructed with a secondary-vertex fit. The $W$ boson is reconstructed from the decay to either an electron or a muon and the missing transverse momentum present in the event. The charmed mesons reconstructed are D+ → K– π+ π+ and D*+ → D0 π+ → (K– π+) π+ and the charge conjugate decays in the fiducial regions where $p$T($e,μ$) > 30 GeV, |$η(e,μ)$| < 2.5, $p$T (D(*)) > 8 GeV, and |$η$(D(*))| < 2.2. The integrated and normalized differential cross sections as a function of the pseudorapidity of the lepton from the $W$ boson decay, and of the transverse momentum of the charmed hadron, are extracted from the data using a profile likelihood fit. The measured total fiducial cross sections are ${σ}_{fid}^{OS – SS}$ (W– + D+) = 50.2 ± 0.2 ${(stat)}_{–2.3}^{+2.4}$(syst) pb, ${σ}_{fid}^{OS – SS}$ (W+ + D–) = 48.5 ± 0.2 ${(stat)}_{–2.2}^{+2.3}$(syst) pb, ${σ}_{fid}^{OS – SS}$ (W– + D*+) = 51.1 ± 0.4 ${(stat)}_{–1.8}^{+1.9}$(syst) pb, ${σ}_{fid}^{OS – SS}$ (W+ + D*–) = 50.0 ± 0.4 ${(stat)}_{–1.8}^{+1.9}$(syst) pb. Results are compared with the predictions of next-to-leading-order quantum chromodynamics calculations performed using state-of-the-art parton distribution functions. Additionally, the ratio of charm to anticharm production cross sections is studied to probe the $s$-$\bar{s}$ quark asymmetry. The ratio is found to be ${R}_{c}^{±}$= 0.971 ± 0.006 (stat) ± 0.011 (syst). The ratio and cross-section measurements are consistent with the predictions obtained with parton distribution function sets that have a symmetric $s$-$\bar{s}$ sea, indicating that any $s$-$\bar{s}$ asymmetry in the Bjorken-x region relevant for this measurement is small.
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•Potassium suppresses methanation by enhancing CO adsorption on Ni via forming bridging carbonyls.•Water dissociation on CeO2 is enhanced by potassium which increases water affinity ...to the support.•Increased density of OH groups on K-doped CeO2 support promotes WGS activity.•WGS activity proceeds via dual-site redox mechanism on Ni/5K/CeO2 catalyst.
The effect of potassium (K) loading on ceria-supported nickel (Ni/xK/CeO2) catalysts on the water–gas shift reaction has been investigated. An optimum loading of 5wt.% K was found to enhance the catalytic performance in terms of activity and selectivity. As evidenced by DRIFTS, the methane-suppressing effect of K is attributed to inhibition of the formation of nickel subcarbonyl species through interaction of Ni and K, coupled with strong adsorption of carbon monoxide (CO) on Ni via the formation of bridging carbonyls. Additionally, K was found to enhance reduction of CeO2 via XANES and promote water dissociation on reduced CeO2 to form hydroxyl (OH) groups, which dissociate further into adsorbed oxygen that reacts with adsorbed CO on Ni to form adsorbed carbon dioxide (CO2). A dual-site redox mechanism was proposed and a good fit of the kinetic data with R2=0.91 was obtained with the proposed kinetic model.
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•CO2 hydrogenation to methanol on Ga-Pd/SiO2 catalysts is highly selective.•Pd2Ga nanoparticles are produced after reduction at 723 K.•Bimetallic particles are in contact with Ga2O2 ...thin layers.•Carbonaceous species on Ga2O3 are hydrogenated via spillover.
A series of palladium (2 wt.%) catalysts supported on silica (301 m2/g) and loaded with increasing amount of gallium – ratio of Ga/Pd = 2, 4 and 8 atom/atom – were investigated for CO2 hydrogenation to methanol. The turnover frequency to methanol (H2/CO2 = 3; 523 K, 3 MPa), based on surface palladium, showed a 200-fold enhancement as compared to the monometallic Pd/SiO2 catalyst. Additionally, the apparent activation energy for methanol synthesis decreased from 60 kJ/mol on Pd/SiO2 to ∼40 kJ/mol on the supported Ga-Pd catalysts. Characterization of the Pd-Ga catalyst series by X-ray absorption spectroscopy and high resolution transmission electron microscopy indicates the formation of Pd2Ga bimetallic nanoparticles partially covered by a thin layer of Ga2O3 on the silica surface. In situ infrared spectroscopy was employed to examine the reaction mechanism during the CO2 adsorption and hydrogenation at 0.7 MPa. It is proposed a bifunctional pathway where the carbonaceous species bound to the gallium oxide surface are hydrogenated, stepwise, to formate and methoxy groups by atomic hydrogen, which spillovers from the Pd-Ga bimetallic nanoparticles.
The concept of using ibuprofen as an albumin-binding entity was recently demonstrated by the development of
LuLu-Ibu-PSMA-01. In the present study, we designed a novel ibuprofen-containing ...radioligand (Ibu-PSMA-02) with subtle structural changes regarding the linker entity in order to investigate a potential impact on the in vitro and in vivo properties. Ibu-PSMA-02 was prepared using solid-phase synthesis techniques and labeled with lutetium-177.
LuLu-Ibu-PSMA-02 was evaluated in vitro with regard to its plasma protein-binding properties, PSMA affinity and uptake into PSMA-expressing PC-3 PIP tumor cells. The tissue distribution profile of
LuLu-Ibu-PSMA-02 was assessed in tumor-bearing mice and dose estimations were performed. The in vitro characteristics of
LuLu-Ibu-PSMA-02 were similar to those previously obtained for
LuLu-Ibu-PSMA-01 with respect to plasma protein-binding, PSMA affinity and tumor cell uptake. The in vivo studies revealed, however, an unprecedentedly high uptake of
LuLu-Ibu-PSMA-02 in PC-3 PIP tumors, resulting in an increased absorbed tumor dose of 7.7 Gy/MBq as compared to 5.1 Gy/MBq calculated for
LuLu-Ibu-PSMA-01. As a consequence of the high tumor accumulation,
LuLu-Ibu-PSMA-02 showed higher tumor-to-background ratios than
LuLu-Ibu-PSMA-01. This study exemplified that smallest structural changes in the linker entity of PSMA radioligands may have a significant impact on their pharmacokinetic profiles and, thus, may be applied as a means for ligand design optimization.
Ni catalysts promoted with 0.5 and 1.0 wt% boron were synthesized, characterized and tested during steam methane reforming, to evaluate the effect of boron on the deactivation behavior. Boron adsorbs ...on the
γ-Al
2O
3 support and on the Ni particles and 1.0 wt% boron is found to enhance the stability without compromising the activity. Catalytic studies at 800 °C, 1 atm, a stoichiometric methane to steam ratio, and space velocities of 330,000 cm
3/(h g
cat) show that promotion with 1.0 wt% boron reduces the rate of deactivation by a factor of 3 and increases the initial methane conversion from 56% for the unpromoted catalyst to 61%. Temperature-programmed oxidation (TPO) and scanning electron microscopy (SEM) studies confirm the formation of carbonaceous deposits and illustrate that 1.0 wt% boron reduces the amount of deposited carbon by 80%.
Promotion of a 15 wt% Ni/
γ-Al
2O
3 catalyst with 1.0 wt% B reduces deactivation by carbon deposition 3-fold and increases the initial methane conversion.
Deferoxamine (DFO) therapy has been associated with improved survival of thalassemia patients. However, cardiac disease remains the main cause of death in those patients. In 1995, the oral chelator ...deferiprone became available for clinical use. We compared the occurrence of cardiac disease in patients treated only with DFO and in those whose therapy was switched to deferiprone during the period of observation, from January 31, 1995, to December 31, 2003. All patients with thalassemia major treated in 7 Italian centers who were born between 1970 and 1993 and who had not experienced a cardiac event prior to January 1995 were included. DFO only was given to 359 patients, and 157 patients received deferiprone for part of the time. A total of 3610 patient-years were observed on DFO and 750 on deferiprone. At baseline, the 2 groups were comparable for age and sex, while ferritin levels were significantly higher in patients switched to deferiprone. Fifty-two cardiac events, including 10 cardiac deaths, occurred during therapy with DFO. No cardiac events occurred during deferiprone therapy or within at least 18 months after the end of it. In the setting of a natural history study, deferiprone therapy was associated with significantly greater cardiac protection than deferoxamine in patients with thalassemia major.
It has been repeatedly reported that female patients with thalassemia major survive longer than males and that the difference is due to a lower rate of cardiac disease in females.
We compared the ...cardiac iron load as measured by T2* magnetic resonance imaging in 776 patients (370 males) examined at the National Research Council as part of an Italian cooperative study. We also established normal left ventricular ejection fraction values for our population.
The prevalence of cardiac disease was higher in males than in females (105 males versus 69 females; P < 0.0001). Cardiac T2* was significantly lower in patients with heart dysfunction (P < 0.0001), but no difference was observed according to sex. Twenty males and five females had a history of cardiac arrhythmias. Their cardiac T2* was not significantly lower than that of patients without arrhythmias (24 ms versus 26 ms; P = 0.381), nor was there a difference between sexes. Liver T2* was significantly lower in males and females with heart dysfunction compared to those without. Ferritin levels were higher in patients of both sexes with heart dysfunction without significant differences between males and females. Conclusions Males and females are at the same risk of accumulating iron in their hearts, but females tolerate iron toxicity better, possibly as an effect of reduced sensitivity to chronic oxidative stress.
Summary
Neridronate is a third generation bisphosphonate with established efficacy in metabolic bone disease. In this randomized, open‐label study, 118 adults with β‐thalassaemia and bone mineral ...density (BMD) Z scores ≤−2·0 were randomized 1:1–500 mg calcium with 400 international unis (iu) vitamin D daily or 500 mg calcium with 400 iu vitamin D daily plus neridronate 100 mg intravenously every 90 d. Significant increases in BMD at the lumbar spine and total hip were noted in the neridronate group at 6 and 12 months from baseline (P < 0·001), and values were significantly higher than the control group at both time intervals. Neridronate also significantly decreased serum bone alkaline phosphatase and C‐telopeptide of collagen type 1 levels from as early as 3 months (P = 0·04 and P < 0·001, respectively), reaching significantly lower values at 12 months compared with the control group (P < 0·05). Reductions in back pain and analgesic use were also evident, starting 3 months from commencing treatment. Treatment was well tolerated by all patients. In this largest randomized trial in thalassaemia‐induced osteoporosis to date, neridronate was safe and effective in reducing bone resorption and increasing BMD. The associated reduction in back pain and improved quality of life will encourage adherence to therapy. (Clinicaltrials.gov identifier NCT01140321.)
β-thalassemia is a hereditary disorder with limited approved treatment options; patients experience anemia and its complications, including iron overload. The study aim was to determine whether ...luspatercept could improve anemia and disease complications in patients with β-thalassemia. This open-label, nonrandomized, uncontrolled study consisted of a 24-week dose-finding and expansion stage (initial stage) and a 5-year extension stage, currently ongoing. Sixty-four patients were enrolled; 33 were non–transfusion dependent (mean hemoglobin, <10.0 g/dL; <4 red blood cell RBC units transfused per 8 weeks), and 31 were transfusion dependent (≥4 RBC units per 8 weeks). Patients received 0.2 to 1.25 mg/kg luspatercept subcutaneously every 21 days for ≥5 cycles (dose-finding stage) and 0.8 to 1.25 mg/kg (expansion cohort and 5-year extension). The primary end point was erythroid response, defined as hemoglobin increase of ≥1.5 g/dL from baseline for ≥14 consecutive days (without RBC transfusions) for non–transfusion-dependent patients or RBC transfusion burden reduction ≥20% over a 12-week period vs the 12 weeks before treatment for transfusion-dependent patients. Eighteen non–transfusion-dependent patients (58%) receiving higher dose levels of luspatercept (0.6-1.25 mg/kg) achieved mean hemoglobin increase ≥1.5 g/dL over ≥14 days vs baseline. Twenty-six (81%) transfusion-dependent patients achieved ≥20% reduction in RBC transfusion burden. The most common grade 1 to 2 adverse events were bone pain, headache, and myalgia. As of the cutoff, 33 patients remain on study. In this study, a high percentage of β-thalassemia patients receiving luspatercept had hemoglobin or transfusion burden improvements. These findings support a randomized clinical trial to assess efficacy and safety. This study was registered at www.clinicaltrials.gov as #NCT01749540 and #NCT02268409.
•A high percentage of patients with β-thalassemia had improvement in hemoglobin or transfusion burden after receiving luspatercept.•Findings support a randomized clinical trial to assess the efficacy and safety of luspatercept for treatment of β-thalassemia.
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