The LEXI and SMILE missions will provide soft X‐ray images of the Earth's magnetosheath and cusps after their anticipated launch in 2023 and 2024, respectively. The IBEX mission showed the potential ...of an Energetic Neutral Atom (ENA) instrument to image dayside magnetosheath and cusps, albeit over the long hours required to raster an image with a single pixel imager. Thus, it is timely to discuss the two imaging techniques and relevant science topics. We simulate soft X‐ray and low‐ENA images that might be observed by a virtual spacecraft during two interesting solar wind scenarios: a southward turning of the interplanetary magnetic field and a sudden enhancement of the solar wind dynamic pressure. We employ the OpenGGCM global magnetohydrodynamics model and a simple exospheric neutral density model for these calculations. Both the magnetosheath and the cusps generate strong soft X‐rays and ENA signals that can be used to extract the locations and motions of the bow shock and magnetopause. Magnetopause erosion corresponds closely to the enhancement of dayside reconnection rate obtained from the OpenGGCM model, indicating that images can be used to understand global‐scale magnetopause reconnection. When dayside imagers are installed with high‐ENA inner‐magnetosphere and FUV/UV aurora imagers, we can trace the solar wind energy flow from the bow shock to the magnetosphere and then to the ionosphere in a self‐standing manner without relying upon other observatories. Soft X‐ray and/or ENA imagers can also unveil the dayside exosphere density structure and its response to space weather.
Key Points
Soft X‐ray and Energetic Neutral Atom (ENA) imaging instruments provide an innovative way to visualize the global solar wind‐magnetosphere interaction
High‐cadence, wide field‐of‐view soft X‐ray, and ENA images can capture the motion of the bow shock and magnetopause
The magnetopause motion can reveal the magnetopause reconnection mode on a global scale
Tumor mutational burden (TMB) measurements aid in identifying patients who are likely to benefit from immunotherapy; however, there is empirical variability across panel assays and factors ...contributing to this variability have not been comprehensively investigated. Identifying sources of variability can help facilitate comparability across different panel assays, which may aid in broader adoption of panel assays and development of clinical applications.
Twenty-nine tumor samples and 10 human-derived cell lines were processed and distributed to 16 laboratories; each used their own bioinformatics pipelines to calculate TMB and compare to whole exome results. Additionally, theoretical positive percent agreement (PPA) and negative percent agreement (NPA) of TMB were estimated. The impact of filtering pathogenic and germline variants on TMB estimates was assessed. Calibration curves specific to each panel assay were developed to facilitate translation of panel TMB values to whole exome sequencing (WES) TMB values.
Panel sizes >667 Kb are necessary to maintain adequate PPA and NPA for calling TMB high versus TMB low across the range of cut-offs used in practice. Failure to filter out pathogenic variants when estimating panel TMB resulted in overestimating TMB relative to WES for all assays. Filtering out potential germline variants at >0% population minor allele frequency resulted in the strongest correlation to WES TMB. Application of a calibration approach derived from The Cancer Genome Atlas data, tailored to each panel assay, reduced the spread of panel TMB values around the WES TMB as reflected in lower root mean squared error (RMSE) for 26/29 (90%) of the clinical samples.
Estimation of TMB varies across different panels, with panel size, gene content, and bioinformatics pipelines contributing to empirical variability. Statistical calibration can achieve more consistent results across panels and allows for comparison of TMB values across various panel assays. To promote reproducibility and comparability across assays, a software tool was developed and made publicly available.
•Estimation of TMB varies across different panels, with panel size, gene content and bioinformatics pipelines contributing to empirical variability.•Panel sizes greater than 667Kb are necessary to maintain adequate PPA and NPA for calling TMB high versus TMB low across the range of cutoffs used in practice.•Statistical calibration can achieve more consistent results across panels and allows for comparison of TMB values across various panel assays.
Among high-grade brain tumors, glioblastoma is particularly difficult to treat, in part due to its highly infiltrative nature which contributes to the malignant phenotype and high mortality in ...patients. In order to better understand the signaling pathways underlying glioblastoma invasion, we performed the first large-scale CRISPR-Cas9 loss of function screen specifically designed to identify genes that facilitate cell invasion. We tested 4,574 genes predicted to be involved in trafficking and motility. Using a transwell invasion assay, we discovered 33 genes essential for invasion. Of the 11 genes we selected for secondary testing using a wound healing assay, 6 demonstrated a significant decrease in migration. The strongest regulator of invasion was mitogen-activated protein kinase 4 (MAP4K4). Targeting of MAP4K4 with single guide RNAs or a MAP4K4 inhibitor reduced migration and invasion in vitro. This effect was consistent across three additional patient derived glioblastoma cell lines. Analysis of epithelial-mesenchymal transition markers in U138 cells with lack or inhibition of MAP4K4 demonstrated protein expression consistent with a non-invasive state. Importantly, MAP4K4 inhibition limited migration in a subset of human glioma organotypic slice cultures. Our results identify MAP4K4 as a novel potential therapeutic target to limit glioblastoma invasion.
Gelling is an important way to texturizing, develop novel products, and carry bioactive compounds in the food industry. Some proteins and gums demonstrate gelling character. However, when they are ...mixed, the properties of the resulting gel may be improved even when some gums not gelling alone. There are many reviews in literature centered on protein-polysaccharide interactions and the use of such mixed systems as complexes. Although, the mixed gelation and particularly the effect of gum addition on the gel properties, have been scarcely approached.
This review focused on the most used natural gums for food gelling purposes and their effect on the microstructure, rheological properties, and water retention capacity of mixed gels to serve as a guide for the design of gelling mixed systems. This insight can allow protein-gum-based gel properties to be tuned for specific food applications.
Gum addition to a protein system induces structural changes in the tridimensional red of the gel that can improve its rheological properties and water holding capacity depending on the structure, molecular weight, density, and nature of the charge of the biopolymers used. Additionally, pH, ionic strength, protein-gum ratio and concentration of the gum are critical factors during gel formation.
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•Gums, with or without gelling properties, combined with proteins can form gels.•Microstructure of mixed gels depends on the nature and concentration of gum used.•Addition of gums to protein gels can improve their rheological properties.•Addition of gums can increase the water holding capacity of a protein gel.
Living cells are being extensively studied to build functional tissues that are useful for both fundamental and applied bioscience studies. Increasing evidence suggests that cell-cell adhesion ...controlled by the intercellular cadherin junction plays important roles in the quality of the resulting engineered tissue. These findings prompted efforts to interrogate biological effects of cadherin at a molecular scale; however, few efforts were made to harness the effects of cadherin on cells cultured in an
in vivo
-like three dimensional matrix. To this end, this study reports a hydrogel matrix three dimensionally functionalized with a controlled number of Fc-tagged recombinant N-cadherins (N-Cad-Fc). To retain the desired conformation of N-Cad, these cadherins were immobilized and oriented to the gel by anti-Fc-antibodies chemically coupled to gels. The gels were processed to present N-Cad-Fc in uniaxially aligned microchannels or randomly oriented micropores. Culturing cortical cells in the functionalized gels generated a large fraction of neurons that are functional as indicated by increased intracellular calcium ion concentrations with the microchanneled gel. In contrast, direct N-Cad-Fc immobilization to microchannel or micropore walls of the gel limited the growth of neurons and increased the glial to neuron ratio. The results of this study will be highly useful to organize a wide array of cadherin molecules in a series of biomaterials used for three-dimensional cell culture and to regulate phenotypic activities of tissue-forming cells in an elaborate manner.
Strategy to culture cells in a three dimensional microchanneled hydrogel conjugated with Fc-N-Cad.
The prognosis for high-grade glioma (HGG) remains dismal and the extent of resection correlates with overall survival and progression free disease. Epidermal growth factor receptor (EGFR) is a ...biomarker heterogeneously expressed in HGG. We assessed the feasibility of detecting HGG using near-infrared fluorescent antibody targeting EGFR. Mice bearing orthotopic HGG xenografts with modest EGFR expression were imaged in vivo after systemic panitumumab-IRDye800 injection to assess its tumor-specific uptake macroscopically over 14 days, and microscopically ex vivo. EGFR immunohistochemical staining of 59 tumor specimens from 35 HGG patients was scored by pathologists and expression levels were compared to that of mouse xenografts. Intratumoral distribution of panitumumab-IRDye800 correlated with near-infrared fluorescence and EGFR expression. Fluorescence distinguished tumor cells with 90% specificity and 82.5% sensitivity. Target-to-background ratios peaked at 14 h post panitumumab-IRDye800 infusion, reaching 19.5 in vivo and 7.6 ex vivo, respectively. Equivalent or higher EGFR protein expression compared to the mouse xenografts was present in 77.1% HGG patients. Age, combined with IDH-wildtype cerebral tumor, was predictive of greater EGFR protein expression in human tumors. Tumor specific uptake of panitumumab-IRDye800 provided remarkable contrast and a flexible imaging window for fluorescence-guided identification of HGGs despite modest EGFR expression.
Purpose
Evaluate the impact of gingivitis on oral health-related quality of life (OHRQoL) amongst 12-year-old schoolchildren from Quito, Ecuador.
Methods
We evaluated 998 school children using the ...Community Periodontal Index for gingival bleeding and calculus. OHRQoL was assessed with the Child Perceptions Questionnaire 11–14 (CPQ
11–14
) questionnaire.
Results
Of the 998 schoolchildren, 93% had gingival bleeding and 73% had dental calculus. Schoolchildren with more than one sextant with gingival bleeding had 1.18 times higher mean CPQ
11–14
(RR 1.18, 95% CI 1.11–1.27) than those with none or just one affected sextant. Male schoolchildren presented a 15% lower mean Child Perceptions Questionnaire (CPQ) (RT 0.85; 95% CI 0.76–0.96). Children whose parents had incomplete secondary education had a 15% lower mean CPQ (RT 0.85; 95% CI 0.77–0.94). Bleeding in more than one sextant was significantly associated with worse quality of life in the emotional well-being (RT 1.40, 95% CI 1.03–1.90) and social well-being domains (RT 1.76, 95% CI 1.32–2.34).
Conclusion
Gingival bleeding negatively impacted the OHRQoL of 12-year-old Ecuadorian schoolchildren living in Quito.
Abstract
We present the data release and data reduction process for the Epoch 1 NIRCam observations for the Cosmic Evolution Early Release Science Survey (CEERS). These data consist of NIRCam imaging ...in six broadband filters (F115W, F150W, F200W, F277W, F356W and F444W) and one medium-band filter (F410M) over four pointings, obtained in parallel with primary CEERS MIRI observations. We reduced the NIRCam imaging with the JWST Calibration Pipeline, with custom modifications and reduction steps designed to address additional features and challenges with the data. Here we provide a detailed description of each step in our reduction and a discussion of future expected improvements. Our reduction process includes corrections for known prelaunch issues such as 1/
f
noise, as well as in-flight issues including snowballs, wisps, and astrometric alignment. Many of our custom reduction processes were first developed with prelaunch simulated NIRCam imaging over the full 10 CEERS NIRCam pointings. We present a description of the creation and reduction of this simulated data set in the Appendix. We provide mosaics of the real images in a public release, as well as our reduction scripts with detailed explanations to allow users to reproduce our final data products. These represent one of the first official public data sets released from the Directors Discretionary Early Release Science (DD-ERS) program.
CO elimination through oxidation over highly active and cost-effective catalysts is a way forward for many processes of industrial and environmental importance. In this study, doped CeO2 with ...transition metals (TM = Cu, Co, Mn, Fe, Ni, Zr, and Zn) at a level of 20 at. % was tested for CO oxidation. The oxides were prepared using microwave-assisted sol–gel synthesis to improve catalyst’s performance for the reaction of interest. The effect of heteroatoms on the physicochemical properties (structure, morphology, porosity, and reducibility) of the binary oxides M–Ce–O was meticulously investigated and correlated to their CO oxidation activity. It was found that the catalytic activity (per gram basis or TOF, s–1) follows the order Cu–Ce–O > Ce–Co–O > Ni–Ce–O > Mn–Ce–O > Fe–Ce–O > Ce–Zn–O > CeO2. Participation of mobile lattice oxygen species in the CO/O2 reaction does occur, the extent of which is heteroatom-dependent. For that, state-of-the-art transient isotopic 18O-labeled experiments involving 16O/18O exchange followed by step-gas CO/Ar or CO/O2/Ar switches were used to quantify the contribution of lattice oxygen to the reaction. SSITKA-DRIFTS studies probed the formation of carbonates while validating the Mars–van Krevelen (MvK) mechanism. Scanning transmission electron microscopy-high-angle annular dark field imaging coupled with energy-dispersive spectroscopy proved that the elemental composition of dopants in the individual nanoparticle of ceria is less than their composition at a larger scale, allowing the assessment of the doping efficacy. Despite the similar structural features of the catalysts, a clear difference in the Olattice mobility was also found as well as its participation (as expressed with the α descriptor) in the reaction, following the order αCu > αCo> αMn > αZn. Kinetic studies showed that it is rather the pre-exponential (entropic) factor and not the lowering of activation energy that justifies the order of activity of the solids. DFT calculations showed that the adsorption of CO on the Cu-doped CeO2 surface is more favorable (−16.63 eV), followed by Co, Mn, Zn (−14.46, −4.90, and −4.24 eV, respectively), and pure CeO2 (−0.63 eV). Also, copper compensates almost three times more charge (0.37e −) compared to Co and Mn, ca. 0.13e − and 0.10e −, respectively, corroborating for its tendency to be reduced. Surface analysis (X-ray photoelectron spectroscopy), apart from the oxidation state of the elements, revealed a heteroatom–ceria surface interaction (Oa species) of different extents and of different populations of Oa species.
Nasal obstruction (NO) is defined as the subjective perception of discomfort or difficulty in the passage of air through the nostrils. It is a common reason for consultation in primary and ...specialized care and may affect up to 30%-40% of the population. It affects quality of life (especially sleep) and lowers work efficiency. The aim of this document is to agree on how to treat NO, establish a methodology for evaluating and diagnosing it, and define an individualized approach to its treatment. NO can be unilateral or bilateral, intermittent or persistent and may be caused by local or systemic factors, which may be anatomical, inflammatory, neurological, hormonal, functional, environmental, or pharmacological in origin. Directed study of the medical history and physical examination are key for diagnosing the specific cause. NO may be evaluated using subjective assessment tools (visual analog scale, symptom score, standardized questionnaires) or by objective estimation (active anterior rhinomanometry, acoustic rhinometry, peak nasal inspiratory flow). Although there is little correlation between the results, they may be considered complementary and not exclusive. Assessing the impact on quality of life through questionnaires standardized according to the underlying disease is also advisable. NO is treated according to its cause. Treatment is fundamentally pharmacological (topical and/or systemic) when the etiology is inflammatory or functional. Surgery may be necessary when medical treatment fails to complement or improve medical treatment or when other therapeutic approaches are not possible. Combinations of surgical techniques and medical treatment may be necessary.
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