The structure, thermodynamic and dynamic properties of normal and metastable liquid Ni
2
x
Fe
50−
x
Co
50−
x
alloys were systematically investigated by combining electrostatic levitation (ESL) ...experiments and molecular dynamics (MD) simulations. Their composition dependence and mutual interaction were explored in detail. The actual densities of liquid Ni
90
Fe
5
Co
5
, Ni
80
Fe
10
Co
10
, Ni
70
Fe
15
Co
15
and Ni
60
Fe
20
Co
20
alloys were measured by ESL experiments in a wide temperature range. The simulated densities of these liquid alloys are in good agreement with the corresponding experimental data. The thermodynamic properties show that all these alloys exhibit a negative excess volume and mixing enthalpy. Meanwhile, their pair distribution functions indicate that Fe and Co atoms easily bond with Ni atoms and have a similar characteristic to each other if compared with Ni atoms. Furthermore, the structure factors validate that there exist icosahedral short-range and medium-range orders of Ni-Ni, Fe-Fe, Fe-Co and Co-Co bonds in these liquid alloys. Additionally, the solute diffusion properties reveal that the correlation between dynamic behavior and alloy composition is determined by the diffusion of Fe and Ni atoms.
Organ transplantation from ABO blood group–incompatible (ABOi) donors requires accurate detection, effective removal and subsequent surveillance of antidonor antibodies. Because ABH antigen subtypes ...are expressed differently in various cells and organs, measurement of antibodies specific for the antigen subtypes in the graft is essential. Erythrocyte agglutination, the century‐old assay used clinically, does not discriminate subtype‐specific ABO antibodies and provides limited information on antibody isotypes. We designed and created an ABO‐glycan microarray and demonstrated the precise assessment of both the presence and, importantly, the absence of donor‐specific antibodies in an international study of pediatric heart transplant patients. Specific IgM, IgG, and IgA isotype antibodies to nonself ABH subtypes were detected in control participants and recipients of ABO‐compatible transplants. Conversely, in children who received ABOi transplants, antibodies specific for A subtype II and/or B subtype II antigens—the only ABH antigen subtypes expressed in heart tissue—were absent, demonstrating the fine specificity of B cell tolerance to donor/graft blood group antigens. In contrast to the hemagglutination assay, the ABO‐glycan microarray allows detailed characterization of donor‐specific antibodies necessary for effective transplant management, representing a major step forward in precise ABO antibody detection.
The authors design a novel ABH‐glycan microarray and demonstrate its effectiveness and accuracy in confirming donor‐specific B cell tolerance in a cohort of ABO‐incompatible pediatric heart transplant patients.
Aims. We report the discovery and validation of two TESS exoplanets orbiting faint M dwarfs: TOI-4479b and TOI-2081b. Methods. We jointly analyzed space (TESS mission) and ground-based (MuSCAT2, ...MuSCAT3 and SINISTRO instruments) light curves using our multicolor photometry transit analysis pipeline. This allowed us to compute contamination limits for both candidates and validate them as planet-sized companions. Results. We found TOI-4479b to be a sub-Neptune-sized planet (Rp = 2.82−0.63+0.65 R⊕) and TOI-2081b to be a super-Earth-sized planet (Rp = 2.04−0.54+0.50 R⊕). Furthermore, we obtained that TOI-4479b, with a short orbital period of 1.15890−0.00001+0.00002 days, lies within the Neptune desert and is in fact the largest nearly ultra-short period planet around an M dwarf known to date. Conclusions. These results make TOI-4479b rare among the currently known exoplanet population of M dwarf stars and an especially interesting target for spectroscopic follow-up and future studies of planet formation and evolution.
Calcium carbonate is a common constituent of many natural materials, such as shells and skeletons of marine animals. While it is well-documented that additives (organic and inorganic) modulate the ...crystallization of amorphous calcium carbonate (ACC), the effects of the intrinsic physicochemical characteristics of ACC, such as particle size, shape, and water content on the transformation to crystalline polymorphs, are still poorly understood. Here, we investigate the effect of particle size by preparing ACC nanoparticles with an average size ranging from ∼66 to ∼196 nm using a high-resolution titration setup. Our results show that the particle size determined the polymorph selection in solution; an increasing proportion of vaterite to calcite was observed with decreasing particle size. The polymorph selection was ascribed to a higher apparent solubility of ACC with decreasing particle size, a parameter from which we could determine the surface energy of ACC to be ∼0.33 J/m2. Upon heating, particle size showed the opposite effect, as smaller particles favored a higher crystallization temperature from ACC into (only) calcite. When the particle size was large enough, crystallization occurred concomitantly with the removal of bulk water at lower temperatures, where the smallest particles transformed at ∼310 °C, only after losing the final (surface) water. Our results highlight the importance of particle size as well as the crystallization conditions on the stability and transformation mechanisms of ACC.
Arteriopathy is the leading cause of childhood arterial ischemic stroke. Mechanisms are poorly understood but may include inherent abnormalities of arterial structure. Extracranial dissection is ...associated with connective tissue disorders in adult stroke. Focal cerebral arteriopathy is a common syndrome where pathophysiology is unknown but may include intracranial dissection or transient cerebral arteriopathy. We aimed to quantify cerebral arterial tortuosity in childhood arterial ischemic stroke, hypothesizing increased tortuosity in dissection.
Children (1 month to 18 years) with arterial ischemic stroke were recruited within the Vascular Effects of Infection in Pediatric Stroke (VIPS) study with controls from the Calgary Pediatric Stroke Program. Objective, multi-investigator review defined diagnostic categories. A validated imaging software method calculated the mean arterial tortuosity of the major cerebral arteries using 3-dimensional time-of-flight magnetic resonance angiographic source images. Tortuosity of unaffected vessels was compared between children with dissection, transient cerebral arteriopathy, meningitis, moyamoya, cardioembolic strokes, and controls (ANOVA and post hoc Tukey). Trauma-related versus spontaneous dissection was compared (Student t test).
One hundred fifteen children were studied (median, 6.8 years; 43% women). Age and sex were similar across groups. Tortuosity means and variances were consistent with validation studies. Tortuosity in controls (1.346±0.074; n=15) was comparable with moyamoya (1.324±0.038; n=15; P=0.998), meningitis (1.348±0.052; n=11; P=0.989), and cardioembolic (1.379±0.056; n=27; P=0.190) cases. Tortuosity was higher in both extracranial dissection (1.404±0.084; n=22; P=0.021) and transient cerebral arteriopathy (1.390±0.040; n=27; P=0.001) children. Tortuosity was not different between traumatic versus spontaneous dissections (P=0.70).
In children with dissection and transient cerebral arteriopathy, cerebral arteries demonstrate increased tortuosity. Quantified arterial tortuosity may represent a clinically relevant imaging biomarker of vascular biology in pediatric stroke.
1. Peroxisome proliferator-activated receptors (PPAR) are involved in lipid metabolism through transcriptional regulation of target gene expression. The objective of the current study was to clone ...and characterise the PPARα and PPARγ genes in pigeon. 2. The full-length of 1941-bp PPARα and 1653-bp PPARγ were cloned from pigeons. The two genes were predicted to encode 468 and 475 amino acids, respectively. Both proteins contained two C4-type zinc fingers, a nuclear hormone receptor DNA-binding region signature and a HOLI domain (ligand binding domain of hormone receptors), and had high identities with other corresponding avian genes. 3. Using quantitative real-time PCR, pigeon PPARα gene expression was shown to be high in kidney, liver, gizzard and duodenum whereas PPARγ was predominantly expressed in adipose tissue.
The main phase of the 17 March 2013 storm had excellent coverage from ground‐based instruments and from low‐ and high‐altitude spacecraft, allowing for evaluation of the relations between major storm ...time phenomena that are often considered separately. The shock impact with its concurrent southward interplanetary magnetic field (IMF) immediately drove dramatic poleward expansion of the poleward boundary of the auroral oval (implying strong nightside reconnection), strong auroral activity, and strong penetrating midlatitude convection and ionospheric currents. This was followed by periods of southward IMF driving of electric fields that were at first relatively smooth as often employed in storm modeling but then became extremely bursty and structured associated with equatorward extending auroral streamers. The auroral oval did not expand much further poleward during these two latter periods, suggesting a lower overall nightside reconnection rate than that during the first period and approximate balance with dayside reconnection. Characteristics of these three modes of driving were reflected in horizontal and field‐aligned currents. Equatorward expansion of the auroral oval occurred predominantly during the structured convection mode, when electric fields became extremely bursty. The period of this third mode also approximately corresponded to the time of largest equatorward motion of the ionospheric trough, of apparent transport of high total electron content (TEC) features into the auroral oval from the polar cap, and of largest earthward injection of ions and electrons into the ring current. The enhanced responses of the aurora, currents, TEC, and the ring current indicate a common driving of all these storm time features during the bursty convection mode period.
Key Points
Storm had excellent ground/space data coverage, allowing evaluation of relations between major storm phenomena often considered separately
Identified three southward IMF electric fields driving modes that were reflected in the aurora and ionospheric and field‐aligned currents
The third mode was extremely bursty, giving common driving of auroral and current structures, TEC changes, and ring current injection
Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the ...efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC.
Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib 50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle). The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety.
A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028. The median PFS was 18.0 months in the toripalimab–axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab–axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab–axitinib group and 58.6% of patients in the sunitinib group.
In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile
ClinicalTrials.gov NCT04394975
•Toripalimab plus axitinib provided significantly better PFS than sunitinib as a first-line treatment for advanced RCC.•A significantly higher ORR was found in patients who received toripalimab plus axitinib than those who received sunitinib.•The combination of toripalimab plus axitinib was generally well tolerated.•No new safety signals were identified in the combination outside the known safety profile of toripalimab or axitinib.
Background and objective
Obstructive sleep apnoea (OSA) and hyperlipidaemia are independent risk factors for cardiovascular disease. This study investigates the association between OSA and prevalence ...of hyperlipidaemia in patients of the European Sleep Apnea Database (ESADA) cohort.
Methods
The cross‐sectional analysis included 11 892 patients (age 51.9 ± 12.5 years, 70% male, body mass index (BMI) 31.3 ± 6.6 kg/m2, mean oxygen desaturation index (ODI) 23.7 ± 25.5 events/h) investigated for OSA. The independent odds ratio (OR) for hyperlipidaemia in relation to measures of OSA (ODI, apnoea‐hypopnoea index, mean and lowest oxygen saturation) was determined by means of general linear model analysis with adjustment for important confounders such as age, BMI, comorbidities and study site.
Results
Hyperlipidaemia prevalence increased from 15.1% in subjects without OSA to 26.1% in those with severe OSA, P < 0.001. Corresponding numbers in patients with diabetes were 8.5% and 41.5%, P < 0.001. Compared with ODI quartile I, patients in ODI quartiles II‐IV had an adjusted OR (95% CI) of 1.33 (1.15–1.55), 1.37 (1.17–1.61) and 1.33 (1.12–1.58) (P < 0.001), respectively, for hyperlipidaemia. Obesity was defined as a significant risk factor for hyperlipidaemia. Subgroups of OSA patients with cardio‐metabolic comorbidities demonstrated higher prevalence of HL. In addition, differences in hyperlipidaemia prevalence were reported in European geographical regions with the highest prevalence in Central Europe.
Conclusion
Obstructive sleep apnoea, in particular intermittent hypoxia, was independently associated with the prevalence of hyperlipidaemia diagnosis.
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