Channel matrix plays a critical role in receiver design and ultimate channel performance. To fully describe the channel matrix of a few-mode fiber (FMF), we choose the generalized high-dimensional ...Gell-Mann matrices, an equivalent of the 2-dimensional Pauli matrices used for a single-mode fiber (SMF), as the basis for the channel matrix decomposition. The frequency dependence of channel matrix can be studied in terms of the autocorrelation function (ACF), showing how fast channel changes in frequency domain. In this paper, we derive a canonical stochastic differential equation (SDE) for the FMF channel matrix in the regime of strong coupling. With the SDE, we develop an analytical form for the ACF of FMF channel matrix, from which the channel correlation bandwidth is obtained.
IL-1 causes a marked increase in the degree of expansion of naïve and memory CD4 T cells in response to challenge with their cognate antigen. The response occurs when only specific CD4 T cells can ...respond to IL-1β, is not induced by a series of other cytokines and does not depend on IL-6 or CD-28. When WT cells are primed in IL-1R1⁻/⁻ recipients, IL-1 increases the proportion of cytokine-producing transgenic CD4 T cells, especially IL-17- and IL-4-producing cells, strikingly increases serum IgE levels and serum IgG1 levels. IL-1β enhances antigen-mediated expansion of in vitro primed Th1, Th2, and Th17 cells transferred to IL-1R1⁻/⁻ recipients. The IL-1 receptor antagonist diminished responses to antigen plus lipopolysaccharide (LPS) by almost equal to55%. These results indicate that IL-1β signaling in T cells markedly induces robust and durable primary and secondary CD4 responses.
The treatment of nasopharyngeal carcinoma requires high radiation doses. The balance of the risks of local recurrence owing to inadequate tumor coverage versus the potential damage to the adjacent ...organs at risk (OARs) is of critical importance. With advancements in technology, high target conformality is possible. Nonetheless, to achieve the best possible dose distribution, optimal setting of dose targets and dose prioritization for tumor volumes and various OARs is fundamental. Radiation doses should always be guided by the As Low As Reasonably Practicable principle. There are marked variations in practice. This study aimed to develop a guideline to serve as a global practical reference.
A literature search on dose tolerances and normal-tissue complications after treatment for nasopharyngeal carcinoma was conducted. In addition, published guidelines and protocols on dose prioritization and constraints were reviewed. A text document and preliminary set of variants was circulated to a panel of international experts with publications or extensive experience in the field. An anonymized voting process was conducted to rank the proposed variants. A summary of the initial voting and different opinions expressed by members were then recirculated to the whole panel for review and reconsideration. Based on the comments of the panel, a refined second proposal was recirculated to the same panel. The current guideline was based on majority voting after repeated iteration for final agreement.
Variation in opinion among international experts was repeatedly iterated to develop a guideline describing appropriate dose prioritization and constraints. The percentage of final agreement on the recommended parameters and alternative views is shown. The rationale for the recommendations and the limitations of current evidence are discussed.
Through this comprehensive review of available evidence and interactive exchange of vast experience by international experts, a guideline was developed to provide a practical reference for setting dose prioritization and acceptance criteria for tumor volumes and OARs. The final decision on the treatment prescription should be based on the individual clinical situation and the patient's acceptance of optimal balance of risk.
Genetic profiling represents the future of neuro-oncology but suffers from inadequate biopsies in heterogeneous tumors like Glioblastoma (GBM). Contrast-enhanced MRI (CE-MRI) targets enhancing core ...(ENH) but yields adequate tumor in only ~60% of cases. Further, CE-MRI poorly localizes infiltrative tumor within surrounding non-enhancing parenchyma, or brain-around-tumor (BAT), despite the importance of characterizing this tumor segment, which universally recurs. In this study, we use multiple texture analysis and machine learning (ML) algorithms to analyze multi-parametric MRI, and produce new images indicating tumor-rich targets in GBM.
We recruited primary GBM patients undergoing image-guided biopsies and acquired pre-operative MRI: CE-MRI, Dynamic-Susceptibility-weighted-Contrast-enhanced-MRI, and Diffusion Tensor Imaging. Following image coregistration and region of interest placement at biopsy locations, we compared MRI metrics and regional texture with histologic diagnoses of high- vs low-tumor content (≥80% vs <80% tumor nuclei) for corresponding samples. In a training set, we used three texture analysis algorithms and three ML methods to identify MRI-texture features that optimized model accuracy to distinguish tumor content. We confirmed model accuracy in a separate validation set.
We collected 82 biopsies from 18 GBMs throughout ENH and BAT. The MRI-based model achieved 85% cross-validated accuracy to diagnose high- vs low-tumor in the training set (60 biopsies, 11 patients). The model achieved 81.8% accuracy in the validation set (22 biopsies, 7 patients).
Multi-parametric MRI and texture analysis can help characterize and visualize GBM's spatial histologic heterogeneity to identify regional tumor-rich biopsy targets.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
DNA methylation in the promoters of plant genes sometimes leads to transcriptional repression, and the loss of DNA methylation in methyltransferase mutants results in altered gene expression and ...severe developmental defects. However, many cases of naturally occurring DNA methylation variations have been reported, whereby altered expression of differentially methylated genes is responsible for agronomically important traits. The ability to manipulate plant methylomes to generate epigenetically distinct individuals could be invaluable for breeding and research purposes. Here, we describe "epimutagenesis," a method to rapidly generate DNA methylation variation through random demethylation of the Arabidopsis thaliana genome. This method involves the expression of a human ten-eleven translocation (TET) enzyme, and results in widespread hypomethylation that can be inherited to subsequent generations, mimicking mutants in the maintenance of DNA methyltransferase met1. Application of epimutagenesis to agriculturally significant plants may result in differential expression of alleles normally silenced by DNA methylation, uncovering previously hidden phenotypic variations.
A vast number of materials properties and phenomena are regulated by diffusion. However, diffusion coefficients from experiments and calculations are far from complete. Here, we report a compilation ...of vacancy formation energies (HVaF), vacancy migration energies (HVaM), vacancy activation energies (HVaQ), vacancy concentrations (CVa), and vacancy-mediated self-diffusion coefficients (DVa) as a function of temperature for 82 pure elements in bcc, fcc, and hcp structures by means of a comprehensive first-principles study. We assess the accuracy of four exchange-correlation (X–C) functionals for first-principles calculations, including the local density approximation (LDA), two generalized gradient approximations (PW91 and PBE), and PBEsol – the focus of the present work. To gain temperature-dependent diffusion properties, transition state structure searches are performed by the climbing image nudged elastic band method; and the needed equilibrium properties of energy (E0), volume (V0), bulk modulus (B0) and its pressure derivative (B′) for each structure of each element are estimated via an energy versus volume equation of state. Examination of the predicted quantities and available experimental data indicates that (i) PBEsol is a better selection in terms of getting accurate equilibrium and diffusion properties; (ii) the facility of vacancy migration can be understood from the redistribution of differential charge density, and anomalous energy pathways for vacancy migration are found for hcp Ce, La, Pr, Ti, and Zr within the basal plane; (iii) HVaQ can be predicted well from the melting point of a pure element and in particular a new relationship (HVaQ=B0V0/6), suggesting diffusivity is governed by interatomic bonding strength; and (iv) the computed quantities such as CVa, DVa, HVaF, HVaM, and HVaQ are in favorable accord with available experiments for most elements, but fall short for entropy-related properties. The present study of pure elements provides not only diffusion-related properties and a new understanding of diffusivity, but also a benchmark of first-principles calculations and a foundational dataset for the Materials Genome Initiative.
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Glacial diamictites deposited in the Mesoarchean, Paleoproterozoic, Neoproterozoic, and Paleozoic eras record temporal variations in their average compositions that reflect the changing composition ...of the upper continental crust (UCC). Twenty six of the 27 units studied show elevated chemical index of alternation (CIA) and low Sr abundances, regardless of their age, documenting pervasive weathering of the average UCC. Lower abundances of transition metals reflect a shift towards more felsic crustal compositions after the Archean. Superimposed on this chemical difference is the signal of the rise of oxidative weathering of the continents, recorded by changes in the absolute and relative abundances of the redox sensitive elements Mo and V. Neoproterozoic and Paleozoic diamictites show pervasive depletion in Mo and V, reflecting their loss from the continents due to increasing intensity of oxidative weathering, as also recorded in some of the Paleoproterozoic diamictites. A few of the Paleoproterozoic diamictites deposited after the Great Oxidation Event show no depletion in Mo and V (e.g., Gowganda), but such signatures could be inherited from their provenance. In contrast, the pre-GOE Duitschland diamictite (ca. 2.3–2.5 Ga) from South Africa reveals evidence of intense oxidative weathering (i.e., large depletions in Mo), supporting a growing body of observations showing the presence of measurable atmospheric oxygen prior to permanent loss of the mass independent fractionation signal in sulfur isotopes.
•Evolution of upper continental crust tracked by glacial tillites of different ages.•Crust has become more felsic with time.•Progressive depletion of Mo, V, and Cr tracks rise of oxidative weathering.•Evidence for some oxidative weathering before GOE from Duitschland Formation.
Objectives
To examine the relation between prenatal urinary phthalate metabolite concentrations and preterm birth (PTB).
Methods
The data were drawn from the Maternal-Infant Research on Environmental ...Chemicals (MIREC) Study, a pan-Canadian cohort of 1857 pregnant women enrolled between 2008 and 2011. We quantified urinary concentrations of 7 phthalate metabolites that were detected in > 70% of urine samples collected during the first trimester. Gestational age was obtained from either the last menstrual period or early ultrasound. We used Cox proportional hazard models to examine the associations of urinary phthalate metabolite concentrations, plus the molar sum of di-2-ethylhexyl phthalate metabolites (∑DEHP), with time to delivery before 37 weeks of gestation. We also examined PTB by clinical presentation. PTBs presented with either spontaneous labour or premature rupture of the membrane were considered spontaneous PTB (sPTB). Additionally, we used multiple linear regression to model changes in mean gestational age in relation to phthalate exposure.
Results
We found no evidence of an association between first trimester phthalate metabolite concentrations and PTB among the MIREC study participants. For example, each 2-fold increase in any of the 7 phthalate concentrations or ∑DEHP was associated with hazard ratios (HRs) for PTB ranging from 0.95 to 1.07 with 95% confidence intervals including the null. An assessment of non-linear trends showed some evidence of non-monotonic dose-response relationships between phthalates and PTB. Furthermore, male infants exposed to MCPP showed higher sPTB risk compared with female infants.
Conclusion
Phthalate exposure during early pregnancy is not clearly associated with the risk of PTB among this Canadian population.
Genome editing of human induced pluripotent stem cells (hiPSCs) offers unprecedented opportunities for in vitro disease modeling and personalized cell replacement therapy. The introduction of ...Cas9-directed genome editing has expanded adoption of this approach. However, marker-free genome editing using standard protocols remains inefficient, yielding desired targeted alleles at a rate of ∼1-5%. We developed a protocol based on a doxycycline-inducible Cas9 transgene carried on a piggyBac transposon to enable robust and highly efficient Cas9-directed genome editing, so that a parental line can be expeditiously engineered to harbor many separate mutations. Treatment with doxycycline and transfection with guide RNA (gRNA), donor DNA and piggyBac transposase resulted in efficient, targeted genome editing and concurrent scarless transgene excision. Using this approach, in 7 weeks it is possible to efficiently obtain genome-edited clones with minimal off-target mutagenesis and with indel mutation frequencies of 40-50% and homology-directed repair (HDR) frequencies of 10-20%.
Background Endobronchial ultrasonography (EBUS)-guided transbronchial needle aspiration allows for sampling of mediastinal lymph nodes. The external diameter, rigidity, and angulation of the convex ...probe EBUS renders limited accessibility. This study compares the accessibility and transbronchial needle aspiration capability of the prototype thin convex probe EBUS against the convex probe EBUS in human ex vivo lungs rejected for transplant. Methods The prototype thin convex probe EBUS (BF-Y0055; Olympus, Tokyo, Japan) with a thinner tip (5.9 mm), greater upward angle (170 degrees), and decreased forward oblique direction of view (20 degrees) was compared with the current convex probe EBUS (6.9-mm tip, 120 degrees, and 35 degrees, respectively). Accessibility and transbronchial needle aspiration capability was assessed in ex vivo human lungs declined for lung transplant. The distance of maximum reach and sustainable endoscopic limit were measured. Transbronchial needle aspiration capability was assessed using the prototype 25G aspiration needle in segmental lymph nodes. Results In all evaluated lungs (n = 5), the thin convex probe EBUS demonstrated greater reach and a higher success rate, averaging 22.1 mm greater maximum reach and 10.3 mm further endoscopic visibility range than convex probe EBUS, and could assess selectively almost all segmental bronchi (98% right, 91% left), demonstrating nearly twice the accessibility as the convex probe EBUS (48% right, 47% left). The prototype successfully enabled cytologic assessment of subsegmental lymph nodes with adequate quality using the dedicated 25G aspiration needle. Conclusions Thin convex probe EBUS has greater accessibility to peripheral airways in human lungs and is capable of sampling segmental lymph nodes using the aspiration needle. That will allow for more precise assessment of N1 nodes and, possibly, intrapulmonary lesions normally inaccessible to the conventional convex probe EBUS.
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