Recent studies suggest overestimates in current U.S. emission inventories of nitrogen oxides (NO x = NO + NO2). Here, we expand a previously developed fuel-based inventory of motor-vehicle emissions ...(FIVE) to the continental U.S. for the year 2013, and evaluate our estimates of mobile source emissions with the U.S. Environmental Protection Agency’s National Emissions Inventory (NEI) interpolated to 2013. We find that mobile source emissions of NO x and carbon monoxide (CO) in the NEI are higher than FIVE by 28% and 90%, respectively. Using a chemical transport model, we model mobile source emissions from FIVE, and find consistent levels of urban NO x and CO as measured during the Southeast Nexus (SENEX) Study in 2013. Lastly, we assess the sensitivity of ozone (O3) over the Eastern U.S. to uncertainties in mobile source NO x emissions and biogenic volatile organic compound (VOC) emissions. The ground-level O3 is sensitive to reductions in mobile source NO x emissions, most notably in the Southeastern U.S. and during O3 exceedance events, under the revised standard proposed in 2015 (>70 ppb, 8 h maximum). This suggests that decreasing mobile source NO x emissions could help in meeting more stringent O3 standards in the future.
Miniaturization in electronics through improvements in established "top-down" fabrication techniques is approaching the point where fundamental issues are expected to limit the dramatic increases in ...computing seen over the past several decades. Here we report a "bottom-up" approach in which functional device elements and element arrays have been assembled from solution through the use of electronically well-defined semiconductor nanowire building blocks. We show that crossed nanowire p-n junctions and junction arrays can be assembled in over 95% yield with controllable electrical characteristics, and in addition, that these junctions can be used to create integrated nanoscale field-effect transistor arrays with nanowires as both the conducting channel and gate electrode. Nanowire junction arrays have been configured as key OR, AND, and NOR logic-gate structures with substantial gain and have been used to implement basic computation.
No standard of care for mucosal melanoma (MM) in the adjuvant setting has been established. Meanwhile, relapse-free survival (RFS) is only ∼5 months after surgery alone. This phase II trial aimed to ...compare toripalimab versus high-dose interferon-α2b (HDI) as an adjuvant therapy for resected MM.
From July 2017 to May 2019, 145 patients with resected MM were randomized (1 : 1) to receive HDI (n = 72) or toripalimab (n = 73) for 1 year until disease relapse/distant metastasis, unacceptable toxicity, or withdrawal of consent. The primary endpoint was RFS. The secondary endpoints included distant metastasis-free survival (DMFS), overall survival (OS), and safety.
After a median follow-up of 26.3 months, the number of RFS, OS, and DMFS events was 51 versus 46, 33 versus 29, and 49 versus 44 in the toripalimab arm and the HDI arm, respectively. The median RFS was 13.6 95% confidence interval (CI) 8.31-19.02 months and 13.9 (95% CI 8.28-19.61) months in the toripalimab arm and the HDI arm, respectively. The DMFS was not significantly different between the two arms hazard ratio (HR) 1.00; 95% CI 0.65-1.54. The median OS was 35.1 months (95% CI 27.93 months-not reached) in the toripalimab arm, with no significant difference in all-cause death (HR 1.11, 95% CI 0.66-1.84) for the two arms. The median sums of the patients’ actual infusion doses were 3672 mg and 1054.5 MIU in the toripalimab arm and the HDI arm, respectively. The incidence of treatment-emergent adverse events with a grade ≥3 was much higher in the HDI arm than in the toripalimab arm (87.5% versus 27.4%).
Toripalimab showed a similar RFS and a more favorable safety profile than HDI, both better than historical data, suggesting that toripalimab might be the better treatment option. However, additional translational studies and better treatment regimens are still warranted to improve the clinical outcome of MM.
•This is the first study to compare toripalimab versus HDI as adjuvant therapy for resected MM.•In PD-L1-positive patients, the median RFS was ∼6 months longer in the toripalimab arm than in the HDI arm.•The incidence of TEAEs with a grade ≥3 was much higher in the HDI arm than in the toripalimab arm.•Both interventions have potential for MM; toripalimab might be the better treatment option.
Abstract With increasing age, the competence of the immune system to fight infections and tumors declines. Age-dependent changes have been mostly described for human CD8 T cells, raising the question ...of whether the response patterns for CD4 T cells are different. Gene expression arrays of memory CD4 T cells yielded a similar age-induced fingerprint as has been described for CD8 T cells. In cross-sectional studies, the phenotypic changes were not qualitatively different for CD4 and CD8 T cells, but occurred much more frequently in CD8 T cells. Homeostatic stability partially explained this lesser age sensitivity of CD4 T cells. With aging, naïve and central memory CD8 T cells were lost at the expense of phenotypically distinct CD8 effector T cells, while effector CD4 T cells did not accumulate. However, phenotypic shifts on central memory T cells were also more pronounced in CD8 T cells. This distinct stability in cell surface marker expression can be reproduced in vitro. The data show that CD8 T cells are age sensitive by at least two partially independent mechanisms: fragile homeostatic control and gene expression instability in a large set of regulatory cell surface molecules.
Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom ...high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P < 5.0 × 10
) with PrCa and one locus significantly associated with early-onset PrCa (≤55 years). Our findings include missense variants rs1800057 (odds ratio (OR) = 1.16; P = 8.2 × 10
; G>C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10
; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa
.
Photovoltaic cells based on arrays of semiconductor nanowires promise efficiencies comparable or even better than their planar counterparts with much less material. One reason for the high ...efficiencies is their large absorption cross section, but until recently the photocurrent has been limited to less than 70% of the theoretical maximum. Here we enhance the absorption in indium phosphide (InP) nanowire solar cells by employing broadband forward scattering of self-aligned nanoparticles on top of the transparent top contact layer. This results in a nanowire solar cell with a photovoltaic conversion efficiency of 17.8% and a short-circuit current of 29.3 mA/cm2 under 1 sun illumination, which is the highest reported so far for nanowire solar cells and among the highest reported for III–V solar cells. We also measure the angle-dependent photocurrent, using time-reversed Fourier microscopy, and demonstrate a broadband and omnidirectional absorption enhancement for unpolarized light up to 60° with a wavelength average of 12% due to Mie scattering. These results unambiguously demonstrate the potential of semiconductor nanowires as nanostructures for the next generation of photovoltaic devices.
Chiral NH functionalities-based discrimination is a key feature of Nature’s chemical armory, yet selective binding of biologically active molecules in synthetic systems with high enantioselectivity ...poses significant challenges. Here we report the assembly of three chiral fluorescent Zn6L6 metallacycles from pyridyl-functionalized Zn(salalen) or Zn(salen) complexes. Each of these metallacycles has a nanoscale hydrophobic cavity decorated with six, three, or zero chiral NH functionalities and packs into a three-dimensional supramolecular porous framework. The binding affinity and enantioselectivity of the metallacycles toward α-hydroxycarboxylic acids, amino acids, small molecule pharamaceuticals (l-dopa, d-penicillamine), and chiral amines increase with the number of chiral NH moieties in the cyclic structure. From single-crystal X-ray diffraction, molecular simulations, and quantum chemical calculations, the chiral recognition and discrimination are attributed to the specific binding of enantiomers in the chiral pockets of the metallacycles. The parent metallacycles are fluorescent with the intensity of emission being linearly related to the enantiomeric composition of the chiral biorelevant guests, which allow them to be utilized in chiral sensing. The fact that manipulation of chiral NH functionalities in metallacycles can control the enantiorecognition of biomolecular complexes would facilitate the design of more effective supramolecular assemblies for enantioselective processes.
By thermal oxidation treatment at 500°C in air, the monoclinic ZrO2 and orthorhombic ZrTiO4 oxide coatings were in-situ formed on the surfaces of biomedical Zr–20Ti and Zr–40Ti alloys, respectively. ...The hardness and adhesion strength of the oxide coatings were measured by indentation and scratching tests. The electrochemical corrosion of the Zr–xTi alloys before and after thermal oxidation treatment was performed in the acidified artificial saliva containing 0.1% NaF at 37°C. The friction and wear performances of the un-oxidized and oxidized Zr–xTi alloys were evaluated by reciprocating ball-on-disc wear tests under the load of 10N. The results show that the oxide coatings have the hardness of 1420–1480HV and the adhesion forces of 51N to the substrates. The oxidized Zr–xTi alloys exhibit the reduced corrosion rates and improved pitting corrosion resistance in comparison with the un-oxidized Zr–xTi alloys. The wear tests demonstrate that the un-oxidized Zr–xTi alloys show the serious adhesive wear and abrasive wear due to the high plasticity and chemical activity. The coefficients of friction and wear rates of the oxidized Zr–xTi alloys decrease 30% and 90%, respectively, which are attributed to the hard oxide coatings with enhanced toughness. Nevertheless, the scabies defects in the oxide coating of Zr–20Ti alloy have a negative effect on the friction and wear property. The oxidized Zr–40Ti alloy has the excellent chemical stability and anti-abrasion performance. It has a great application prospect as dental implant material.
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•The oxide coatings rapidly form on Zr20Ti and Zr40Ti by heat treatment at 500°C.•Increasing Ti content promotes the formation of ZrTiO4 phase in the coating.•The coatings possess high hardness and good adhesion force to the substrates.•The coatings obviously improve the anti-corrosion in the medium containing fluoride.•The oxidized Zr40Ti alloy exhibits better anti-wear performance.
Obesity-related brain structural abnormalities have been reported extensively, and bariatric surgery (BS) is currently the most effective intervention to produce sustained weight reduction in overtly ...obese (OB) people. It is unknown whether BS can repair the brain circuitry abnormalities concomitantly with long-term weight loss.
In order to investigate whether BS promotes neuroplastic structural recovery in morbidly OB patients, we quantified fractional anisotropy (FA), mean diffusivity (MD) and gray (GM) and white (WM) matter densities in 15 morbidly OB patients and in 18 normal weight (NW) individuals. OB patients were studied at baseline and also 1 month after laparoscopic sleeve gastrectomy surgery.
Two-sample t-test between OB (baseline) and NW groups showed decreased FA values, GM/WM densities and increased MD value in brain regions associated with food intake control (that is, caudate, orbitofrontal cortex, body and genu of corpus callosum) and cognitive-emotion regulation (that is, inferior frontal gyrus, hippocampus, insula, external capsule) (P<0.05, family-wise error correction). Paired t-test in the OB group between before and after surgery showed that BS generated partial neuroplastic structural recovery in the OB group, but the differences had relative less strength and smaller volume (P<0.001).
This study provides the first anatomical evidence for BS-induced acute neuroplastic recovery that might in part mediate the long-term benefit of BS in weight reduction. It also highlights the importance of this line of gut-brain axis research employing the combined BS and neuroimaging model for identifying longitudinal changes in brain structure that correlated with obesity status.
We use a global chemical transport model (GEOS‐Chem) to interpret aircraft curtain observations of black carbon (BC) aerosol over the Pacific from 85°N to 67°S during the 2009–2011 HIAPER ...(High‐Performance Instrumented Airborne Platform for Environmental Research) Pole‐to‐Pole Observations (HIPPO) campaigns. Observed concentrations are very low, implying much more efficient scavenging than is usually implemented in models. Our simulation with a global source of 6.5 Tg a−1 and mean tropospheric lifetime of 4.2 days (versus 6.8 ± 1.8 days for the Aerosol Comparisons between Observations and Models (AeroCom) models) successfully simulates BC concentrations in source regions and continental outflow and captures the principal features of the HIPPO data but is still higher by a factor of 2 (1.48 for column loads) over the Pacific. It underestimates BC absorbing aerosol optical depths (AAODs) from the Aerosol Robotic Network by 32% on a global basis. Only 8.7% of global BC loading in GEOS‐Chem is above 5 km, versus 21 ± 11% for the AeroCom models, with important implications for radiative forcing estimates. Our simulation yields a global BC burden of 77 Gg, a global mean BC AAOD of 0.0017, and a top‐of‐atmosphere direct radiative forcing (TOA DRF) of 0.19 W m−2, with a range of 0.17–0.31 W m−2 based on uncertainties in the BC atmospheric distribution. Our TOA DRF is lower than previous estimates (0.27 ± 0.06 W m−2 in AeroCom, 0.65–0.9 W m−2 in more recent studies). We argue that these previous estimates are biased high because of excessive BC concentrations over the oceans and in the free troposphere.
Key Points
A global distribution of BC is simulated in GEOS‐Chem
Results imply more efficient BC removal than is usually included in models
Previous estimates of DRF from BC were biased high due to excessive remote BC
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