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This study of manganese (Mn, Z = 25) introduces a novel combination of extended‐range high energy resolution fluorescence detection (XR‐HERFD), multiple‐crystal spectrometers and advanced binary data splicing techniques to address challenges in X‐ray emission spectroscopy. XR‐HERFD enhances spectral precision by utilizing high‐resolution crystal analysers and optimized detector configurations. The systematic application of these methods using multiple Bragg crystal analysers at Diamond Light Source has led to substantial improvements in data quality. Simultaneously, advanced binary data splicing integrates multiple datasets to correct distortions and improve resolution, resulting in sharper spectral features. Our results show a significant increase in peak counts and a notable reduction in full width at half‐maximum (FWHM), with peak amplitudes increasing by 83% and resolution improving by 46%. These developments provide greater detail for X‐ray absorption or emission spectra, offering valuable insights into complex materials, and permitting advances and breakthroughs in atomic relativistic quantum mechanics, chemical sensitivity of atomic transitions and modelling of solid‐state effects. A robust integration is introduced of the extended‐range high energy resolution fluorescence detection technique, multiple‐crystal spectrometers and binary data splicing techniques for the further refinement of spectra in X‐ray emission spectroscopy, revealing deeper insights into material properties and atomic transitions.

The propagation of wave fields and their interactions with matter are important for established and emerging fields in optical sciences. Efficient methods for predicting such behaviour have been employed routinely for coherent sources. However, most real world optical systems exhibit partial coherence, for which the present mathematical description involves high dimensional complex functions and hence poses challenges for numerical implementations. This demands significant computational resources to determine the properties of partially coherent wavefields. Here, we describe the novel Phase-Space (PS) propagator, an efficient and self-consistent technique for free space propagation of wave fields which are partially coherent in the spatial domain. The PS propagator makes use of the fact that the propagation of a wave field in free space is equivalent to a shearing of the corresponding PSD function. Computationally, this approach is simpler and the need for using different propagation methods for near and far-field regions is removed.

The recent update on the US National Ambient Air Quality Standards (NAAQS) of the ground-level ozone (O3) can benefit from a better understanding of its source contributions in different US regions during recent years. In the Hemispheric Transport of Air Pollution experiment phase 1 (HTAP1), various global models were used to determine the O3 source–receptor (SR) relationships among three continents in the Northern Hemisphere in 2001. In support of the HTAP phase 2 (HTAP2) experiment that studies more recent years and involves higher-resolution global models and regional models' participation, we conduct a number of regional-scale Sulfur Transport and dEposition Model (STEM) air quality base and sensitivity simulations over North America during May–June 2010. STEM's top and lateral chemical boundary conditions were downscaled from three global chemical transport models' (i.e., GEOS-Chem, RAQMS, and ECMWF C-IFS) base and sensitivity simulations in which the East Asian (EAS) anthropogenic emissions were reduced by 20 %. The mean differences between STEM surface O3 sensitivities to the emission changes and its corresponding boundary condition model's are smaller than those among its boundary condition models, in terms of the regional/period-mean (< 10 %) and the spatial distributions. An additional STEM simulation was performed in which the boundary conditions were downscaled from a RAQMS (Realtime Air Quality Modeling System) simulation without EAS anthropogenic emissions. The scalability of O3 sensitivities to the size of the emission perturbation is spatially varying, and the full (i.e., based on a 100 % emission reduction) source contribution obtained from linearly scaling the North American mean O3 sensitivities to a 20 % reduction in the EAS anthropogenic emissions may be underestimated by at least 10 %. The three boundary condition models' mean O3 sensitivities to the 20 % EAS emission perturbations are ∼ 8 % (May–June 2010)/∼ 11 % (2010 annual) lower than those estimated by eight global models, and the multi-model ensemble estimates are higher than the HTAP1 reported 2001 conditions. GEOS-Chem sensitivities indicate that the EAS anthropogenic NOx emissions matter more than the other EAS O3 precursors to the North American O3, qualitatively consistent with previous adjoint sensitivity calculations. In addition to the analyses on large spatial–temporal scales relative to the HTAP1, we also show results on subcontinental and event scales that are more relevant to the US air quality management. The EAS pollution impacts are weaker during observed O3 exceedances than on all days in most US regions except over some high-terrain western US rural/remote areas. Satellite O3 (TES, JPL–IASI, and AIRS) and carbon monoxide (TES and AIRS) products, along with surface measurements and model calculations, show that during certain episodes stratospheric O3 intrusions and the transported EAS pollution influenced O3 in the western and the eastern US differently. Free-running (i.e., without chemical data assimilation) global models underpredicted the transported background O3 during these episodes, posing difficulties for STEM to accurately simulate the surface O3 and its source contribution. Although we effectively improved the modeled O3 by incorporating satellite O3 (OMI and MLS) and evaluated the quality of the HTAP2 emission inventory with the Royal Netherlands Meteorological Institute–Ozone Monitoring Instrument (KNMI–OMI) nitrogen dioxide, using observations to evaluate and improve O3 source attribution still remains to be further explored.

Spondyloarthropathies are characterized by a distinct pattern of inflammation at distinct anatomical sites and are associated with elevated expression of interleukin 23 (IL-23). Daniel Cua and his colleagues identify an IL-23–responsive CD4 − CD8 − T cell population located within entheses. Systemic overexpression of IL-23 activates these cells and recapitulates aspects of the human disease in mice, and neutralization of IL-17 and IL-22 decreases pathology, suggesting new therapeutic targets for these disorders. The spondyloarthropathies are a group of rheumatic diseases that are associated with inflammation at anatomically distal sites, particularly the tendon-bone attachments (entheses) and the aortic root. Serum concentrations of interleukin-23 (IL-23) are elevated and polymorphisms in the IL-23 receptor are associated with ankyosing spondylitis, however, it remains unclear whether IL-23 acts locally at the enthesis or distally on circulating cell populations. We show here that IL-23 is essential in enthesitis and acts on previously unidentified IL-23 receptor (IL-23R) + , RAR-related orphan receptor γt (ROR-γt) + CD3 + CD4 − CD8 − , stem cell antigen 1 (Sca1) + entheseal resident T cells. These cells allow entheses to respond to IL-23 in vitro —in the absence of further cellular recruitment—and to elaborate inflammatory mediators including IL-6, IL-17, IL-22 and chemokine (C-X-C motif) ligand 1 (CXCL1). Notably, the in vivo expression of IL-23 is sufficient to phenocopy the human disease, with the specific and characteristic development of enthesitis and entheseal new bone formation in the initial complete absence of synovitis. As in the human condition, inflammation also develops in vivo at the aortic root and valve, which are structurally similar to entheses. The presence of these entheseal resident cells and their production of IL-22, which activates signal transducer and activator of transcription 3 (STAT3)-dependent osteoblast-mediated bone remodeling, explains why dysregulation of IL-23 results in inflammation at this precise anatomical site.

Chronic inflammation has been associated with increased risk for developing gastrointestinal cancer. Interleukin-23 (IL-23) receptor signaling has been correlated with inflammatory bowel disease pathogenesis, as well as promotion of tumor growth. However, little is known about the relative potential for IL-23-directed causality in gut tumorigenesis. We report that IL-23 transgene expression was sufficient to induce rapid (3–4 weeks) de novo development of intestinal adenomas with 100% incidence. Initiation of tumorigenesis was independent of exogenous carcinogens, Helicobacter colonization, or pre-existing tumor-suppressor gene mutations. Tumorigenesis was mediated by Thy1+IL-23R+ innate lymphoid cells (ILC3), in part, through IL-17 responses as tumor development was inhibited in RAG−/− × IL-17−/− double knockout mice. Remarkably, IL-23 initiation of tumorigenesis by resident ILCs consistently occurred before recruitment of conspicuous inflammatory infiltrates. Our results reveal an explicit role for IL-23-mediated initiation of gut tumorigenesis and implicate a key role for IL-23R+ ILC3 in the absence of overt cellular infiltrate recruitment.

We review the progress of tropospheric trace gas observations and address the need for additional measurement capabilities as recommended by the National Research Council. Tropospheric measurements show pollution in the Northern Hemisphere as a result of fossil fuel burning and a strong seasonal dependence with the largest amounts of carbon monoxide and nitrogen dioxide in the winter and spring. In the summer, when photochemistry is most intense, photochemically generated ozone is found in large concentrations over and downwind from where anthropogenic sources are largest, such as the eastern United States and eastern China. In the tropics and the subtropics, where photon flux is strong throughout the year, trace gas concentrations are driven by the abundance of the emissions. The largest single tropical source of pollution is biomass burning, as can be seen readily in carbon monoxide measurements, but lightning and biogenic trace gases may also contribute to trace gas variability. Although substantive progress has been achieved in seasonal and global mapping of a few tropospheric trace gases, satellite trace gas observations with considerably better temporal and spatial resolution are essential to forecasting air quality at the spatial and temporal scales required by policy makers. The concurrent use of atmospheric composition measurements for both scientific and operational purposes is a new paradigm for the atmospheric chemistry community. The examples presented illustrate both the promise and challenge of merging satellite information with in situ observations in state-of-the-art data assimilation models.

Leaf shape varies spectacularly among plants. Leaves are the primary source of photoassimilate in crop plants, and understanding the genetic basis of variation in leaf morphology is critical to improving agricultural productivity. Leaf shape played a unique role in cotton improvement, as breeders have selected for entire and lobed leaf morphs resulting from a single locus, okra (L-D₁), which is responsible for the major leaf shapes in cotton. The L-D₁ locus is not only of agricultural importance in cotton, but through pioneering chimeric and morphometric studies, it has contributed to fundamental knowledge about leaf development. Here we show that an HD-Zip transcription factor homologous to the LATE MERISTEM IDENTITY1 (LMI1) gene of Arabidopsis is the causal gene underlying the L-D₁ locus. The classical okra leaf shape allele has a 133-bp tandem duplication in the promoter, correlated with elevated expression, whereas an 8-bp deletion in the third exon of the presumed wild-type normal allele causes a frame-shifted and truncated coding sequence. Our results indicate that subokra is the ancestral leaf shape of tetraploid cotton that gave rise to the okra allele and that normal is a derived mutant allele that came to predominate and define the leaf shape of cultivated cotton. Virus-induced gene silencing (VIGS) of the LMI1-like gene in an okra variety was sufficient to induce normal leaf formation. The developmental changes in leaves conferred by this gene are associated with a photosynthetic transcriptomic signature, substantiating its use by breeders to produce a superior cotton ideotype.

The impacts of transported background (TBG) pollutants on western US ozone (O3) distributions in summer 2008 are studied using the multi-scale Sulfur Transport and dEposition Modeling system. Forward sensitivity simulations show that TBG contributes ~30–35 ppb to the surface Monthly mean Daily maximum 8-h Average O3 (MDA8) over Pacific Southwest (US Environmental Protection Agency (EPA) Region 9, including California, Nevada and Arizona) and Pacific Northwest (EPA Region 10, including Washington, Oregon and Idaho), and ~10–17 ppm-h to the secondary standard metric \"W126 monthly index\" over EPA Region 9 and ~3–4 ppm-h over Region 10. The strongest TBG impacts on W126 occur over the grass/shrub-covered regions. Among TBG pollutants, O3 is the major contributor to surface O3, while peroxyacetyl nitrate is the most important O3 precursor species. W126 shows larger responses than MDA8 to perturbations in TBG and stronger non-linearity to the magnitude of perturbations. The TBG impacts on both metrics overall negatively correlate to model vertical resolution and positively correlate to the horizontal resolution. The mechanisms that determine TBG contributions and their variation are analyzed using trajectories and the receptor-based adjoint sensitivity analysis, which demonstrate the connection between the surface O3 and O3 aloft (at ~1–4 km) 1–2 days earlier. The probabilities of airmasses originating from Mt. Bachelor (2.7 km) and 2.5 km above Trinidad Head (THD) entraining into the boundary layer reach daily maxima of 66% and 34% at ~03:00 p.m. Pacific Daylight Time (PDT), respectively, and stay above 50% during 09:00 a.m.–04:00 p.m. PDT for those originating 1.5 km above California's South Coast. Assimilation of the surface in-situ measurements significantly reduced the errors in the modeled surface O3 during a long-range transport episode by ~5 ppb on average (up to ~17 ppb) and increased the estimated TBG contributions by ~3 ppb. Available O3 vertical profiles from Tropospheric Emission Spectrometer (TES), Ozone Monitoring Instrument (OMI) and THD sonde identified this transport event, but assimilation of these observations in this case did not efficiently improve the O3 distributions except near the sampling locations, due to their limited spatiotemporal resolution and/or possible uncertainties.

A major objective of the 2006 Second Texas Air Quality Study (TexAQS II) focused on understanding the effects of regional processes on Houston and Dallas ozone nonattainment areas. Here we quantify the contributions of background (continental scale) ozone production on Houston and Dallas air quality during TexAQS II using ensemble Lagrangian trajectories to identify remote source regions that impact Houston and Dallas background ozone distributions. Global‐scale chemical analyses, constrained with composition measurements from instruments on the NASA Aura satellite, are used to provide estimates of background composition along ensemble back trajectories. Lagrangian averaged O3 net photochemical production (production minus loss, P‐L) rates along the back trajectories are used as a metric to classify back trajectories. Results show that the majority (6 out of 9 or 66%) of the periods of high ozone in Houston were associated with periods of enhanced background ozone production. Slightly less than 50% (7 out of 15) of the days with high ozone in the Dallas Metropolitan Statistical Area (MSA) show enhanced background ozone production. Source apportionment studies show that 5‐day Lagrangian averaged O3 P‐L in excess of 15 ppbv/d can occur during continental‐scale transport to Houston owing to NOy enhancements from emissions within the Southern Great Lakes as well as recirculation of the Houston emissions. Dallas background O3 P‐L is associated with NOy enhancements from emissions within Chicago and Houston.

Interleukin-23 (IL-23) has emerged as a new therapeutic target for the treatment of inflammatory bowel disease (IBD). As biomarkers of disease state and treatment efficacy are becoming increasingly important in drug development, we sought to identify efficacy biomarkers for anti-IL-23 therapy in Crohn's disease (CD). Candidate IL-23 biomarkers, downstream of IL-23 signaling, were identified using shotgun proteomic analysis of feces and colon lavages obtained from a short-term mouse IBD model (anti-CD40 Rag2(-/-)) treated preventively with monoclonal antibodies (mAbs) to the IL-23 receptor (IL-23R). The biomarkers were then measured in an IBD T-cell transfer model treated therapeutically with a mAb to IL-23 (p19), confirming their association with IBD. To assess the clinical relevance of these markers, we assessed their concentrations in clinical serum, colon tissue, and feces from CD patients. We identified 57 proteins up or downregulated in diseased animals that returned to control values when the mice were treated with mAbs to IL-23R. Among those, S100A8, S100A9, regenerating protein 3β (REG), REG3γ, lipocalin 2 (LCN2), deleted in malignant tumor 1 (DMBT1), and macrophage migration inhibitory factor (MIF) mRNA levels correlated with disease score and dose titration of mAbs to IL-23R or IL-23(p19). All biomarkers, except DMBT1, were also downregulated after therapeutic administration of mAbs to IL-23(p19) in a T-cell transfer IBD mouse model. In sera from CD patients, we confirmed a significant upregulation of S100A8/A9 (43%), MIF (138%), pancreatitis-associated protein (PAP, human homolog of REG3β/γ; 49%), LCN2 (520%), and CCL20 (1280%), compared with control samples, as well as a significant upregulation of S100A8/A9 (887%), PAP (401%), and LCN2 (783%) in human feces from CD patients compared with normal controls. These studies identify multiple protein biomarkers downstream of IL-23 that could be valuable tools to assess the efficacy of this new therapeutic agent.Clinical and Translational Gastroenterology (2012) 3, e10; doi:10.1038/ctg.2012.2; published online 16 February 2012.