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Flight crews’ capacity to conduct take-off and landing in near zero visibility conditions has been partially addressed by advanced surveillance and cockpit display technology. This capability is yet to be realised within the context of manoeuvring aircraft within airport terminal areas. In this paper the performance and workload benefits of user-centre designed visual and haptic taxi navigational cues, presented via a head-up display (HUD) and active sidestick, respectively, were evaluated in simulated taxiing trials by 12 professional pilots. In addition, the trials sought to examine pilot acceptance of side stick nose wheel steering. The HUD navigational cues demonstrated a significant task-specific benefit by reducing centreline deviation during turns and the frequency of major taxiway deviations. In parallel, the visual cues reduced self-report workload. Pilot’s appraisal of nose wheel steering by sidestick was positive, and active sidestick cues increased confidence in the multimodal guidance construct. The study presents the first examination of how a multimodal display, combining visual and haptic cues, could support the safety and efficiency in which pilots are able to conduct a taxi navigation task in low-visibility conditions.
Belief in biological races remains prevalent in the early 21st century despite opposing logical arguments and an abundance of converging evidence from multiple scientific disciplines. Structural and interpersonal racism, among the most salient issues today, are empowered and perpetuated by false claims and misconceptions about human origins, kinships, and differences. The best current science and historical knowledge make clear that races are cultural inventions that are not aligned with biological realities. Acknowledging the errors and falsehoods that provide the framework for biological race belief is not an attempt to deny real genetic variation or the importance of cultural races. This chapter reviews critical challenges to biological race belief and presents examinations of three of the most contentious and confounding race topics: IQ tests and intelligence, health and healthcare disparities, and sports as a popular source of misinterpretation and confusion. An evidence-based perception of humankind offers both laypersons and scientists a more productive position from which to understand our diversity and alleviate racism.
Understanding the distribution and geometry of faults and fractures is critical for predicting both subsurface permeability architecture and the integrity of geological fluid barriers, particularly in rocks with low primary porosity and permeability. While fracture patterns in relatively competent, weathering-resistant (therefore often well-exposed) rocks are generally well studied in outcrop, the role of mechanically weak layers in defining fracture patterns is frequently overlooked or under-represented. Here we show that rock composition, specifically clay and silicate minerals versus carbonate content, exerts a strong control on fault and fracture propagation and bed-containment within a mechanically layered, Cretaceous carbonate sequence at Canyon Lake Gorge, Texas. We find that relatively incompetent, clay-rich layers limit fault and fracture propagation, and cause bed-containment of fractures in more competent beds. In our results, no clear relationships exist between mechanical layer thickness and fracture abundance. These results are important for understanding the relative importance of composition versus bed thickness on fracture abundance in the subsurface, and for predicting fracture-controlled fluid flow pathways, seals and fracture connectivity across beds with variable compositions, thicknesses and competences.
OBJECTIVES/GOALS: Evaluate the migration and immune suppressive functions of CCR2+/CX3CR1+ myeloid-derived suppressor cells (MDSCs). Integrate experimental data and biologically relevant mathematical models of infiltrating MDSCs in the context of glioblastoma (GBM). METHODS/STUDY POPULATION: CCR2+/CX3CR1+ cells were enriched from bone marrow obtained from CCR2(+/RFP)/CX3CR1(+/GFP) glioma-bearing mice to evaluate their immune-suppressive phenotype and ability to migrate to CCL2 and CCL7. Fluorescent imaging and quantification were performed on a range of tumor sizes to acquire vasculature, tumor, T cell, and MDSC densities. A system of ordinary differential equations was constructed to represent the temporal dynamics of glioma cells, T cells, and MDSCs within the tumor microenvironment. The Approximate Bayesian Computation method was used to determine probability distributions of important parameters, such as the suppression rate of T cells by MDSCs. RESULTS/ANTICIPATED RESULTS: CCR2+/CX3CR1+ M-MDSCs isolated from the bone marrow of tumor-bearing mice suppress CD8+ T cell proliferation and IFNγ production. CCR2+/CX3CR1+ cells migrate to recombinant and KR158B glioma sourced CCL2 and CCL7. Parameter values determined by the Approximate Bayesian Computation method agreed with parameter values from experimental data. This result further validated the structure and results of the mathematical model when performing computer simulations; thus, we can predict CCR2+/CX3CR1+ M-MDSC infiltration over time. DISCUSSION/SIGNIFICANCE: The immune-suppressive microenvironment in GBM contributes to poor outcomes despite standard of care. This study integrates biological and mathematical models to better understand infiltrating immune-suppressive cells, namely CCR2+/CX3CR1+ M-MDSCs. Future directions include modeling immunotherapies.
ABSTRACT IMPACT: Predicting therapeutic responses in GBM. OBJECTIVES/GOALS: The goal of this team approach is to integrate mathematical models of glioblastoma (GBM) infiltrating myeloid cells that contribute to the immunosuppressive phenotype in glioma with experimental data to predict therapeutic responses to combined chemokine receptor and immune checkpoint blockade. METHODS/STUDY POPULATION: Orthotopic murine KR158-luc gliomas were established in fluorescent reporter CCR2WT/RFP CX3CR1WT/GFP mice. Subsequently, an anti-CD31 injection was administered to label the vasculature. Fluorescent imaging and quantification of anti-CD3 stained sections were performed on a range of tumor sizes to acquire vasculature, tumor, T cell, and myeloid cell densities. In parallel, a system of ordinary differential equations was formulated based on biological assumptions to evaluate the change over time of tumor cells, T cells, and infiltrating myeloid cells. The model was then refined and validated by experimental results. RESULTS/ANTICIPATED RESULTS: Fluorescent imaging and quantification revealed a correlation between tumor size and abundance of (CX3CR1+, CCR2-) and (CX3CR1+, CCR2+) myeloid cell populations in the tumor microenvironment. The density of these cell populations and vasculature remained constant as the tumors increased in size. Computer simulations of the mathematical model will predict tumor, myeloid, and T cell dynamics. These simulations will be particularly useful to uncover information regarding myeloid cell dynamics, such as cell entry time into the tumor microenvironment. Parameter sensitivity analysis of the model will inform us of the biological processes driving these tumor-immune cell dynamics. DISCUSSION/SIGNIFICANCE OF FINDINGS: GBM is a challenge as current intervention are ineffective. This study improves the understanding of glioma infiltrating myeloid cells and their impact on tumor progression. The data will serve as a basis for quantitatively predicting therapeutic responses of a novel combination treatment.
Depression and overweight are each associated with abnormal immune system activation. We sought to disentangle the extent to which depressive symptoms and overweight status contributed to increased inflammation and abnormal cortisol levels.
Methods
Participants were recruited through the Wellcome Trust NIMA Consortium. The sample of 216 participants consisted of 69 overweight patients with depression; 35 overweight controls; 55 normal-weight patients with depression and 57 normal-weight controls. Peripheral inflammation was measured as high-sensitivity C-Reactive Protein (hsCRP) in serum. Salivary cortisol was collected at multiple points throughout the day to measure cortisol awakening response and diurnal cortisol levels.
Results
Overweight patients with depression had significantly higher hsCRP compared with overweight controls (p = 0.042), normal-weight depressed patients (p < 0.001) and normal-weight controls (p < 0.001), after controlling for age and gender. Multivariable logistic regression showed that comorbid depression and overweight significantly increased the risk of clinically elevated hsCRP levels ⩾3 mg/L (OR 2.44, 1.28–3.94). In a separate multivariable logistic regression model, overweight status contributed most to the risk of having hsCRP levels ⩾3 mg/L (OR 1.52, 0.7–2.41), while depression also contributed a significant risk (OR 1.09, 0.27–2). There were no significant differences between groups in cortisol awakening response and diurnal cortisol levels.
Conclusion
Comorbid depression and overweight status are associated with increased hsCRP, and the coexistence of these conditions amplified the risk of clinically elevated hsCRP levels. Overweight status contributed most to the risk of clinically elevated hsCRP levels, but depression also contributed to a significant risk. We observed no differences in cortisol levels between groups.
The El Cañizar de Villarquemado pollen record covers the last part of MIS 6 to the Late Holocene. We use Tolerance-Weighted Averaging Partial Least Squares (TWA-PLS) to reconstruct mean temperature of the coldest month (MTCO) and growing degree days above 0°C (GDD0) and the ratio of annual precipitation to annual potential evapotranspiration (MI), accounting for the ecophysiological effect of changing CO2 on water-use efficiency. Rapid summer warming occurred during the Zeifen-Kattegat Oscillation at the transition to MIS 5. Summers were cold during MIS 4 and MIS 2, but some intervals of MIS 3 had summers as warm as the warmest phases of MIS 5 or the Holocene. Winter temperatures declined from MIS 4 to MIS 2. Changes in temperature seasonality within MIS 5 and MIS 1 are consistent with insolation seasonality changes. Conditions became progressively more humid during MIS 5, and MIS 4 was also humid, although MIS 3 was more arid. Changes in MI and GDD0 are anti-correlated, with increased MI during summer warming intervals. Comparison with other records shows glacial-interglacial changes were not unform across the circum-Mediterranean region, but available quantitative reconstructions are insufficient to determine if east-west differences reflect the circulation-driven precipitation dipole seen in recent decades.
Most techniques for pollen-based quantitative climate reconstruction use modern assemblages as a reference data set. We examine the implication of methodological choices in the selection and treatment of the reference data set for climate reconstructions using Weighted Averaging Partial Least Squares (WA-PLS) regression and records of the last glacial period from Europe. We show that the training data set used is important because it determines the climate space sampled. The range and continuity of sampling along the climate gradient is more important than sampling density. Reconstruction uncertainties are generally reduced when more taxa are included, but combining related taxa that are poorly sampled in the data set to a higher taxonomic level provides more stable reconstructions. Excluding taxa that are climatically insensitive, or systematically overrepresented in fossil pollen assemblages because of known biases in pollen production or transport, makes no significant difference to the reconstructions. However, the exclusion of taxa overrepresented because of preservation issues does produce an improvement. These findings are relevant not only for WA-PLS reconstructions but also for similar approaches using modern assemblage reference data. There is no universal solution to these issues, but we propose a number of checks to evaluate the robustness of pollen-based reconstructions.
Single nucleotide polymorphisms (SNPs) contribute small increases in risk for late-onset Alzheimer's disease (LOAD). LOAD SNPs cluster around genes with similar biological functions (pathways). Polygenic risk scores (PRS) aggregate the effect of SNPs genome-wide. However, this approach has not been widely used for SNPs within specific pathways.
Objectives
We investigated whether pathway-specific PRS were significant predictors of LOAD case/control status.
Methods
We mapped SNPs to genes within 8 pathways implicated in LOAD. For our polygenic analysis, the discovery sample comprised 13,831 LOAD cases and 29,877 controls. LOAD risk alleles for SNPs in our 8 pathways were identified at a P-value threshold of 0.5. Pathway-specific PRS were calculated in a target sample of 3332 cases and 9832 controls. The genetic data were pruned with R2 > 0.2 while retaining the SNPs most significantly associated with AD. We tested whether pathway-specific PRS were associated with LOAD using logistic regression, adjusting for age, sex, country, and principal components. We report the proportion of variance in liability explained by each pathway.
Results
The most strongly associated pathways were the immune response (NSNPs = 9304, = 5.63 × 10−19, R2 = 0.04) and hemostasis (NSNPs = 7832, P = 5.47 × 10−7, R2 = 0.015). Regulation of endocytosis, hematopoietic cell lineage, cholesterol transport, clathrin and protein folding were also significantly associated but accounted for less than 1% of the variance. With APOE excluded, all pathways remained significant except proteasome-ubiquitin activity and protein folding.
Conclusions
Genetic risk for LOAD can be split into contributions from different biological pathways. These offer a means to explore disease mechanisms and to stratify patients.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
We present a detailed overview of the cosmological surveys that we aim to carry out with Phase 1 of the Square Kilometre Array (SKA1) and the science that they will enable. We highlight three main surveys: a medium-deep continuum weak lensing and low-redshift spectroscopic HI galaxy survey over 5 000 deg2; a wide and deep continuum galaxy and HI intensity mapping (IM) survey over 20 000 deg2 from
$z = 0.35$
to 3; and a deep, high-redshift HI IM survey over 100 deg2 from
$z = 3$
to 6. Taken together, these surveys will achieve an array of important scientific goals: measuring the equation of state of dark energy out to
$z \sim 3$
with percent-level precision measurements of the cosmic expansion rate; constraining possible deviations from General Relativity on cosmological scales by measuring the growth rate of structure through multiple independent methods; mapping the structure of the Universe on the largest accessible scales, thus constraining fundamental properties such as isotropy, homogeneity, and non-Gaussianity; and measuring the HI density and bias out to
$z = 6$
. These surveys will also provide highly complementary clustering and weak lensing measurements that have independent systematic uncertainties to those of optical and near-infrared (NIR) surveys like Euclid, LSST, and WFIRST leading to a multitude of synergies that can improve constraints significantly beyond what optical or radio surveys can achieve on their own. This document, the 2018 Red Book, provides reference technical specifications, cosmological parameter forecasts, and an overview of relevant systematic effects for the three key surveys and will be regularly updated by the Cosmology Science Working Group in the run up to start of operations and the Key Science Programme of SKA1.
The Square Kilometre Array (SKA) is a planned large radio interferometer designed to operate over a wide range of frequencies, and with an order of magnitude greater sensitivity and survey speed than any current radio telescope. The SKA will address many important topics in astronomy, ranging from planet formation to distant galaxies. However, in this work, we consider the perspective of the SKA as a facility for studying physics. We review four areas in which the SKA is expected to make major contributions to our understanding of fundamental physics: cosmic dawn and reionisation; gravity and gravitational radiation; cosmology and dark energy; and dark matter and astroparticle physics. These discussions demonstrate that the SKA will be a spectacular physics machine, which will provide many new breakthroughs and novel insights on matter, energy, and spacetime.
Although there are many views on the nature of wisdom, a common thread emerging in philosophical, folk, and scientific discourse is the importance of wise reflection or “reasoning” for sound judgment. In this chapter, we briefly highlight this common thread in historical perspectives on wisdom before moving on to discuss its further development through contemporary personality- and performance-oriented traditions in the empirical study of wisdom. These empirical traditions serve as forerunners to the recent methodological and experimental innovations in the study of wise reasoning. We detail the strengths and weaknesses of existing measures of wisdom, and the subsequent development and validation of the Situated Wise Reasoning Scale to address the limitations of previous approaches. We highlight work demonstrating the importance of the situation for measuring wise reasoning. Further, we address cultural differences in wise reasoning, and highlight ways to boost people’s propensity to reason wisely. Finally, we outline some of the theoretical and practical implications of wise reasoning for wisdom writ large.
Leaf colour characteristics of 730 sweetpotato, Ipomoea batatas (L.) Lam. (Convolvulaceae), plant introduction (PI) accessions from the USDA sweetpotato germplasm collection were evaluated during 2012–2014. Colorimetry data for the abaxial and adaxial leaf surfaces were recorded using a tristimulus colorimeter and the CIE 1976 L*a*b* and CIE L*C*h* colour spaces. Most accessions (725 of 730 PIs) had dark-to-medium green leaves, but two PIs had totally purple leaves, and three PIs had yellow or yellow-green (chartreuse) leaves. For mature, field-grown green leaves, values for the red-green coordinate (a*) averaged −12.4 for the adaxial and −10.4 for the abaxial leaf surface. Values for the blue-yellow coordinate (b*) averaged 17.2 for the adaxial and 17.3 for the abaxial leaf surface. Hue angle (h*) for green leaves averaged 120.9° for the adaxial and 126.2° for the abaxial leaf surface. Colour saturation (Chroma, C*) averaged 21.3 for the adaxial and 20.2 for the abaxial leaf surface. Lightness (L*) averaged 35.4 for the adaxial and 47.2 for the abaxial leaf surface of green leaves. Late in the season, over one-half (53.9%) of the 730 PIs showed some level of purple pigmentation in the leaf lamina. Late-season purple leaves were collected and colour coordinates were recorded for 118 PIs grown in the field. For purple leaves, values for a*, b*, C*, L* and h* averaged 2.3, 6.2, 7.9, 28.2 and 64.4° for the adaxial surface and −1.0, 12.7, 13.9, 43.1 and 87.0° for the abaxial leaf surface, respectively.
Effective integrated weed management in agricultural landscapes depends on the ability to identify and manage processes that drive weed dynamics. The current study reports the effects of grazing management and crop rotation strategies on the seedbank and emerged weed flora in an integrated crop-livestock system (ICLS) experiment during a 12-year period under no-tillage in sub-tropical southern Brazil. During winter, Italian ryegrass cover crops were grazed by sheep: grazing management treatments included two stocking methods (continuous and rotational) and two forage allowances (10 and 20 kg of herbage dry matter available per 100 kg animal live weight). During summer, the crop rotation treatments involved either soybean-maize or soybean-soybean in succession with winter-grazed cover crops. The treatments were part of a factorial randomized complete block design. Treatment effects were evaluated on the weed seedbank and emerged weed flora populations during winter-grazed cover crop and summer crop growth as well as during the harvest phase. The current results demonstrate that crop rotation and grazing management exhibited interactive effects on the determination of weed outcomes in an ICLS. However, overall, compared with moderate forage allowance, high forage allowance during the winter-grazed cover crop caused lower emerged weed flora in subsequent crops (20% reduction during crop growth and 90% reduction at crop harvest) and 48% reduction in seedbank size. High forage allowance promoted more residue from winter-grazed cover crop biomass, which remained during the summer crop phases and probably resulted in a physical barrier to weed emergence.