Remission induction therapy for acute lymphoblastic leukemia (ALL) includes medications that may cause hepatotoxicity, including asparaginase. We used a genome‐wide association study to identify loci ...associated with elevated alanine transaminase (ALT) levels after induction therapy in children with ALL enrolled on St. Jude Children's Research Hospital (SJCRH) protocols. Germline DNA was genotyped using arrays and exome sequencing. Adjusting for age, body mass index, ancestry, asparaginase preparation, and dosage, the PNPLA3 rs738409 (C>G) I148M variant, previously associated with fatty liver disease risk, had the strongest genetic association with ALT (P = 2.5 × 10‐8). The PNPLA3 rs738409 variant explained 3.8% of the variability in ALT, and partly explained race‐related differences in ALT. The PNPLA3 rs738409 association was replicated in an independent cohort of 2,285 patients treated on Children's Oncology Group protocol AALL0232 (P = 0.024). This is an example of a pharmacogenetic variant overlapping with a disease risk variant.
A Nationwide Nitrogen Deposition Monitoring Network (NNDMN) containing 43 monitoring sites was established in China to measure gaseous NH3, NO2, and HNO3 and particulate NH4+ and NO3− in air and/or ...precipitation from 2010 to 2014. Wet/bulk deposition fluxes of Nr species were collected by precipitation gauge method and measured by continuous-flow analyzer; dry deposition fluxes were estimated using airborne concentration measurements and inferential models. Our observations reveal large spatial variations of atmospheric Nr concentrations and dry and wet/bulk Nr deposition. On a national basis, the annual average concentrations (1.3–47.0 μg N m−3) and dry plus wet/bulk deposition fluxes (2.9–83.3 kg N ha−1 yr−1) of inorganic Nr species are ranked by land use as urban > rural > background sites and by regions as north China > southeast China > southwest China > northeast China > northwest China > Tibetan Plateau, reflecting the impact of anthropogenic Nr emission. Average dry and wet/bulk N deposition fluxes were 20.6 ± 11.2 (mean ± standard deviation) and 19.3 ± 9.2 kg N ha−1 yr−1 across China, with reduced N deposition dominating both dry and wet/bulk deposition. Our results suggest atmospheric dry N deposition is equally important to wet/bulk N deposition at the national scale. Therefore, both deposition forms should be included when considering the impacts of N deposition on environment and ecosystem health.
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•Silicon kerf wastes of diamond wire sawing from solar industry were studied.•Remove metals and C by acid leaching and calcination respectively and effectively.•HF was fount effective ...for leaching Ni.•Recycled silicon had a purity of near 5 N.•Use raw materials to make silicon nitride powder and crucibles for solar industry.
With the rapid growth of the global photovoltaic (PV) industry, the waste from PV industry cannot be ignored, especially the solid wastes from silicon kerf loss and the used quartz crucibles from silicon casting. The silicon kerf loss during wafer sawing was nearly 160,000 tonnes and the used crucible waste was nearly 70,000 tonnes in 2017. With the transition of wafering technology from the slurry-based wire to diamond wire sawing, recycling and reuse of kerf-loss silicon have become more feasible due to the lower impurity contents. In this paper, we aimed to find a simple approach to recycle the kerf loss and identify the purity for reuse. We first analyzed the contents of the as-received kerf-loss silicon from the industry. Then, suitable acids and refining procedure were proposed. The metals, especially nickel, could be easily reduced to several ppmw, boron and phosphorous to sub-ppmw, and carbon to several hundred ppmw, while oxygen was less than 5 wt%. Although the purity of the recycled silicon was not sufficient for casting feedstock, it had a comparable purity of about 5 N with the commercial silicon nitride releasing agent and crucibles used in silicon casting for solar cells. Because the nitride crucibles could be reused a few times for casting, the used crucible waste could be significantly reduced as well.
An efficient automated toolkit for predicting the mechanical properties of materials can accelerate new materials design and discovery; this process often involves screening large configurational ...space in high-throughput calculations. Herein, we present the ElasTool toolkit for these applications. In particular, we use the ElasTool to study diversity of 2D materials and heterostructures including their temperature-dependent mechanical properties, and developed a machine learning algorithm for exploring predicted properties.
Dusty star-forming galaxies at high redshift (1 < z < 3) represent the most intense star-forming regions in the universe. Key aspects to these processes are the gas heating and cooling mechanisms, ...and although it is well known that these galaxies are gas-rich, little is known about the gas excitation conditions. Only a few detailed radiative transfer studies have been carried out owing to a lack of multiple line detections per galaxy. Here we examine these processes in a sample of 24 strongly lensed star-forming galaxies identified by the Planck satellite (LPs) at z ∼ 1.1-3.5. We analyze 162 CO rotational transitions (ranging from Jup = 1 to 12) and 37 atomic carbon fine-structure lines (C i) in order to characterize the physical conditions of the gas in the sample of LPs. We simultaneously fit the CO and C i lines and the dust continuum emission, using two different non-LTE, radiative transfer models. The first model represents a two-component gas density, while the second assumes a turbulence-driven lognormal gas density distribution. These LPs are among the most gas-rich, IR-luminous galaxies ever observed ( L L IR ( 8 − 1000 m ) ∼ 10 13 − 14.6 L ; 〈 LMISM 〉 = (2.7 1.2) × 1012 M , with L ∼ 10-30 the average lens magnification factor). Our results suggest that the turbulent interstellar medium present in the LPs can be well characterized by a high turbulent velocity dispersion ( 〈 ΔVturb 〉 ∼ 100 km s−1) and ratios of gas kinetic temperature to dust temperature 〈 Tkin/Td 〉 ∼ 2.5, sustained on scales larger than a few kiloparsecs. We speculate that the average surface density of the molecular gas mass and IR luminosity, M ISM ∼ 103-4 M pc−2 and L IR ∼ 1011-12 L kpc−2, arise from both stellar mechanical feedback and a steady momentum injection from the accretion of intergalactic gas.
We systematically investigate the excitonic dephasing of three representative transition-metal dichalcogenides, namely, MoS_{2}, MoSe_{2}, and WSe_{2} atomic monolayer thick and bulk crystals, in ...order to gain a proper understanding of the factors that determine the optical coherence in these materials. Coherent nonlinear optical spectroscopy and temperature dependent absorption, combined with theoretical calculations of the phonon spectra, indicate electron-phonon interactions, to be the limiting factor. Surprisingly, the excitonic dephasing, differs only slightly between atomic monolayers and high quality bulk crystals, which indicates that material imperfections are not the limiting factor in atomically thin monolayer samples. The temperature dependence of the electronic band gap and the excitonic linewidth combined with "ab initio" calculations of the phonon energies and the phonon density of states reveal a strong interaction with the E' and E" phonon modes.
A global three-dimensional (i.e. latitude, longitude, altitude) climatology of tropospheric ozone is derived from the ozone sounding record by trajectory mapping. Approximately 52 000 ozonesonde ...profiles from more than 100 stations worldwide since 1965 are used. The small number of stations results in a sparse geographical distribution. Here, forward and backward trajectory calculations are performed for each sounding to map ozone measurements to a number of other locations, and so to fill in the spatial domain. This is possible because the lifetime of ozone in the troposphere is of the order of weeks. This physically based interpolation method offers obvious advantages over typical statistical interpolation methods. The trajectory-mapped ozone values show reasonable agreement, where they overlap, to the actual soundings, and the patterns produced separately by forward and backward trajectory calculations are similar. Major regional features of the tropospheric ozone distribution are clearly evident in the global maps. An interpolation algorithm based on spherical functions is further used for smoothing and to fill in remaining data gaps. The resulting three-dimensional global tropospheric ozone climatology facilitates visualization and comparison of different years, decades, and seasons, and offers some intriguing insights into the global variation of tropospheric ozone. It will be useful for climate and air quality model initialization and validation, and as an a priori climatology for satellite data retrievals. Further division of the climatology into decadal and annual averages can provide a global view of tropospheric ozone changes, although uncertainties with regard to the performance of older sonde types, as well as more recent variations in operating procedures, need to be taken into account.
In this study, we describe the development and characterization of the first high‐density single nucleotide polymorphism (SNP) genotyping array for rainbow trout. The SNP array is publically ...available from a commercial vendor (Affymetrix). The SNP genotyping quality was high, and validation rate was close to 90%. This is comparable to other farm animals and is much higher than previous smaller scale SNP validation studies in rainbow trout. High quality and integrity of the genotypes are evident from sample reproducibility and from nearly 100% agreement in genotyping results from other methods. The array is very useful for rainbow trout aquaculture populations with more than 40 900 polymorphic markers per population. For wild populations that were confounded by a smaller sample size, the number of polymorphic markers was between 10 577 and 24 330. Comparison between genotypes from individual populations suggests good potential for identifying candidate markers for populations' traceability. Linkage analysis and mapping of the SNPs to the reference genome assembly provide strong evidence for a wide distribution throughout the genome with good representation in all 29 chromosomes. A total of 68% of the genome scaffolds and contigs were anchored through linkage analysis using the SNP array genotypes, including ~20% of the genome assembly that has not been previously anchored to chromosomes.
Rearranged during transfection (RET) gene fusions are a validated target in non-small-cell lung cancer (NSCLC). RET-selective inhibitors selpercatinib (LOXO-292) and pralsetinib (BLU-667) recently ...demonstrated favorable antitumor activity and safety profiles in advanced RET fusion-positive NSCLC, and both have received approval by the US Food and Drug Administration for this indication. Insights into mechanisms of resistance to selective RET inhibitors remain limited.
This study was performed at five institutions. Tissue and/or cell-free DNA was obtained from patients with RET fusion-positive NSCLC after treatment with selpercatinib or pralsetinib and assessed by next-generation sequencing (NGS) or MET FISH.
We analyzed a total of 23 post-treatment tissue and/or plasma biopsies from 18 RET fusion-positive patients who received an RET-selective inhibitor (selpercatinib, n = 10; pralsetinib, n = 7; pralsetinib followed by selpercatinib, n = 1, with biopsy after each inhibitor). Three cases had paired tissue and plasma samples, of which one also had two serial resistant tissue specimens. The median progression-free survival on RET inhibitors was 6.3 months 95% confidence interval 3.6–10.8 months. Acquired RET mutations were identified in two cases (10%), both affecting the RET G810 residue in the kinase solvent front. Three resistant cases (15%) harbored acquired MET amplification without concurrent RET resistance mutations, and one specimen had acquired KRAS amplification. No other canonical driver alterations were identified by NGS. Among 16 resistant tumor specimens, none had evidence of squamous or small-cell histologic transformation.
RET solvent front mutations are a recurrent mechanism of RET inhibitor resistance, although they occurred at a relatively low frequency. The majority of resistance to selective RET inhibition may be driven by RET-independent resistance such as acquired MET or KRAS amplification. Next-generation RET inhibitors with potency against RET resistance mutations and combination strategies are needed to effectively overcome resistance in these patients.
•Resistance is a major challenge in RET fusion-positive lung cancer treated with RET tyrosine kinase inhibitors (TKIs).•RET mutations involving the solvent front residue G810 are a recurrent yet infrequent mechanism of resistance to RET TKIs.•The majority of resistance to selective RET inhibition is driven by RET-independent resistance, such as MET amplification.•RET TKIs with potency against RET solvent front mutations and combination strategies are needed to overcome resistance.
The TSIS‐1 Hybrid Solar Reference Spectrum Coddington, O. M.; Richard, E. C.; Harber, D. ...
Geophysical research letters,
28 June 2021, Letnik:
48, Številka:
12
Journal Article
Recenzirano
Odprti dostop
We present a new solar irradiance reference spectrum representative of solar minimum conditions between solar cycles 24 and 25. The Total and Spectral Solar Irradiance Sensor‐1 (TSIS‐1) Hybrid Solar ...Reference Spectrum (HSRS) is developed by applying a modified spectral ratio method to normalize very high spectral resolution solar line data to the absolute irradiance scale of the TSIS‐1 Spectral Irradiance Monitor (SIM) and the CubeSat Compact SIM (CSIM). The high spectral resolution solar line data are the Air Force Geophysical Laboratory ultraviolet solar irradiance balloon observations, the ground‐based Quality Assurance of Spectral Ultraviolet Measurements In Europe Fourier transform spectrometer solar irradiance observations, the Kitt Peak National Observatory solar transmittance atlas, and the semi‐empirical Solar Pseudo‐Transmittance Spectrum atlas. The TSIS‐1 HSRS spans 202–2730 nm at 0.01 to ∼0.001 nm spectral resolution with uncertainties of 0.3% between 460 and 2365 nm and 1.3% at wavelengths outside that range.
Plain Language Summary
The Sun's irradiance spectrum is used in many applications, such as constraining the solar forcing in climate models and converting measured satellite radiance to reflectance. A growing body of literature has provided evidence that the currently available solar reference spectra differ by more than their reported uncertainties. Such differences lead to biased results when different reference spectra are adopted in the aforementioned applications. This motivates our work to provide a new high‐resolution solar reference spectrum at higher accuracy than any previously reported. Our ability to produce such a data set is due to the state‐of‐the‐art measurements of the Sun's irradiance spectrum made since March 2018 by the next‐generation Spectral Irradiance Monitor (SIM) instrument on the Total and Spectral Solar Irradiance Sensor‐1 (TSIS‐1) satellite mission and the Compact SIM (CSIM) technology demonstration mission. The TSIS‐1 SIM and CSIM have order‐of‐magnitude reduction in uncertainty relative to predecessor instruments primarily because of a first‐of‐its‐kind spectral radiometric calibration facility capable of characterizing the instruments to higher fidelity. We develop this new, high‐resolution, solar irradiance reference spectrum by adjusting high spectral resolution solar line data to the irradiance scale of the more accurate, but lower spectral resolution, TSIS‐1 SIM and CSIM observations.
Key Points
The TSIS‐1 Spectral Irradiance Monitor and Compact SIM instruments observe the Sun's irradiance spectrum at high accuracy
The TSIS‐1 Hybrid Solar Reference Spectrum consists of high resolution solar line data normalized to the TSIS‐1 SIM irradiance spectrum
The TSIS‐1 Hybrid Solar Reference Spectrum has at least 0.01 nm spectral resolution, spans 202–2730 nm, and is accurate to 0.3%–1.3%
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