105 research outputs found

    Genomic differentiation during speciation-with-gene-flow: Comparing geographic and host-related variation in divergent life history adaptation in rhagoletis pomonella

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    A major goal of evolutionary biology is to understand how variation within populations gets partitioned into differences between reproductively isolated species. Here, we examine the degree to which diapause life history timing, a critical adaptation promoting population divergence, explains geographic and host-related genetic variation in ancestral hawthorn and recently derived apple-infesting races of Rhagoletis pomonella. Our strategy involved combining experiments on two different aspects of diapause (initial diapause intensity and adult eclosion time) with a geographic survey of genomic variation across four sites where apple and hawthorn flies co-occur from north to south in the Midwestern USA. The results demonstrated that the majority of the genome showing significant geographic and host-related variation can be accounted for by initial diapause intensity and eclosion time. Local genomic differences between sympatric apple and hawthorn flies were subsumed within broader geographic clines; allele frequency differences within the races across the Midwest were two to three-fold greater than those between the races in sympatry. As a result, sympatric apple and hawthorn populations displayed more limited genomic clustering compared to geographic populations within the races. The findings suggest that with reduced gene flow and increased selection on diapause equivalent to that seen between geographic sites, the host races may be recognized as different genotypic entities in sympatry, and perhaps species, a hypothesis requiring future genomic analysis of related sibling species to R. pomonella to test. Our findings concerning the way selection and geography interplay could be of broad significance for many cases of earlier stages of divergence-with-gene flow, including (1) where only modest increases in geographic isolation and the strength of selection may greatly impact genetic coupling and (2) the dynamics of how spatial and temporal standing variation is extracted by selection to generate differences between new and discrete units of biodiversity

    Standing geographic variation in eclosion time and the genomics of host race formation in Rhagoletis pomonella fruit flies.

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    Taxa harboring high levels of standing variation may be more likely to adapt to rapid environmental shifts and experience ecological speciation. Here, we characterize geographic and host-related differentiation for 10,241 single nucleotide polymorphisms in Rhagoletis pomonella fruit flies to infer whether standing genetic variation in adult eclosion time in the ancestral hawthorn (Crataegus spp.)-infesting host race, as opposed to new mutations, contributed substantially to its recent shift to earlier fruiting apple (Malus domestica). Allele frequency differences associated with early vs. late eclosion time within each host race were significantly related to geographic genetic variation and host race differentiation across four sites, arrayed from north to south along a 430-km transect, where the host races co-occur in sympatry in the Midwest United States. Host fruiting phenology is clinal, with both apple and hawthorn trees fruiting earlier in the North and later in the South. Thus, we expected alleles associated with earlier eclosion to be at higher frequencies in northern populations. This pattern was observed in the hawthorn race across all four populations; however, allele frequency patterns in the apple race were more complex. Despite the generally earlier eclosion timing of apple flies and corresponding apple fruiting phenology, alleles on chromosomes 2 and 3 associated with earlier emergence were paradoxically at lower frequency in the apple than hawthorn host race across all four sympatric sites. However, loci on chromosome 1 did show higher frequencies of early eclosion-associated alleles in the apple than hawthorn host race at the two southern sites, potentially accounting for their earlier eclosion phenotype. Thus, although extensive clinal genetic variation in the ancestral hawthorn race exists and contributed to the host shift to apple, further study is needed to resolve details of how this standing variation was selected to generate earlier eclosing apple fly populations in the North

    Interior Regularity Estimates in High Conductivity Homogenization and Application

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    In this paper, uniform pointwise regularity estimates for the solutions of conductivity equations are obtained in a unit conductivity medium reinforced by a epsilon-periodic lattice of highly conducting thin rods. The estimates are derived only at a distance epsilon^{1+tau} (for some tau>0) away from the fibres. This distance constraint is rather sharp since the gradients of the solutions are shown to be unbounded locally in L^p as soon as p>2. One key ingredient is the derivation in dimension two of regularity estimates to the solutions of the equations deduced from a Fourier series expansion with respect to the fibres direction, and weighted by the high-contrast conductivity. The dependence on powers of epsilon of these two-dimensional estimates is shown to be sharp. The initial motivation for this work comes from imaging, and enhanced resolution phenomena observed experimentally in the presence of micro-structures. We use these regularity estimates to characterize the signature of low volume fraction heterogeneities in the fibred reinforced medium assuming that the heterogeneities stay at a distance epsilon^{1+tau} away from the fibres

    Mechanical Behavior and Microstructural Development of Low-Carbon Steel and Microcomposite Steel Reinforcement Bars Deformed under Quasi-Static and Dynamic Shear Loading

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    Reinforcement bars of microcomposite (MC) steel, composed of lath martensite and minor amounts of retained austenite, possess improved strength and corrosion characteristics over low-carbon (LC) steel rebar; however, their performance under shear loading has not previously been investigated at the microstructural level. In this study, LC and MC steel cylinders were compression tested, and specimens machined into a forced-shear geometry were subjected to quasi-static and dynamic shear loading to determine their shear behavior as a function of the strain and strain rate. The as-received and sheared microstructures were examined using optical microscopy (OM), scanning electron microscopy (SEM), and electron backscatter diffraction (EBSD). Higher-resolution microstructural examinations were performed using transmission electron microscopy (TEM). The influence of the starting microstructure on the shear behavior was found to depend strongly on the strain rate; the MC steel exhibited not only greater strain-rate sensitivity than the LC steel but also a greater resistance to shear localization with load. In both steels, despite differences in the starting microstructure, post-mortem observations were consistent with a continuous mechanism operating within adiabatic shear bands (ASBs), in which subgrains rotated into highly misoriented grains containing a high density of dislocations

    Feasibility of implementing the patient-reported outcomes version of the common terminology criteria for adverse events in a multicenter trial: NCCTG N1048

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    Purpose The US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was developed to enable patient reporting of symptomatic adverse events in oncology clinical research. This study was designed to assess the feasibility and resource requirements associated with implementing PRO-CTCAE in a multicenter trial. Methods Patients with locally advanced rectal cancer enrolled in the National Cancer Institute-sponsored North Central Cancer Treatment Group (Alliance) Preoperative Radiation or Selective Preoperative Radiation and Evaluation before Chemotherapy and Total Mesorectal Excision trial were asked to self-report 30 PRO-CTCAE items weekly from home during preoperative therapy, and every 6 months after surgery, via either the Web or an automated telephone system. If participants did not self-report within 3 days, a central coordinator called them to complete the items. Compliance was defined as the proportion of participants who completed PRO-CTCAE assessments at expected time points. Results The prespecified PRO-CTCAE analysis was conducted after the 500th patient completed the 6-month follow-up (median age, 56 years; 33% female; 12% nonwhite; 43% high school education or less; 5% Spanish speaking), across 165 sites. PRO-CTCAE was reported by participants at 4,491 of 4,882 expected preoperative time points (92.0% compliance), of which 3,771 (77.2%) were selfreported by participants and 720 (14.7%) were collected via central coordinator backup. Compliance at 6-month post-treatment follow-up was 333 of 468 (71.2%), with 122 (26.1%) via backup. Site research associates spent a median of 15 minutes on PRO-CTCAE work for each patient visit. Work by a central coordinator required a 50% time commitment. Conclusion Home-based reporting of PRO-CTCAE in a multicenter trial is feasible, with high patient compliance and low site administrative requirements. PRO-CTCAE data capture is improved through centralized backup calls

    HighP–TNano-Mechanics of Polycrystalline Nickel

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    We have conducted highP–Tsynchrotron X-ray and time-of-flight neutron diffraction experiments as well as indentation measurements to study equation of state, constitutive properties, and hardness of nanocrystalline and bulk nickel. Our lattice volume–pressure data present a clear evidence of elastic softening in nanocrystalline Ni as compared with the bulk nickel. We show that the enhanced overall compressibility of nanocrystalline Ni is a consequence of the higher compressibility of the surface shell of Ni nanocrystals, which supports the results of molecular dynamics simulation and a generalized model of a nanocrystal with expanded surface layer. The analytical methods we developed based on the peak-profile of diffraction data allow us to identify “micro/local” yield due to high stress concentration at the grain-to-grain contacts and “macro/bulk” yield due to deviatoric stress over the entire sample. The graphic approach of our strain/stress analyses can also reveal the corresponding yield strength, grain crushing/growth, work hardening/softening, and thermal relaxation under highP–Tconditions, as well as the intrinsic residual/surface strains in the polycrystalline bulks. From micro-indentation measurements, we found that a low-temperature annealing (T < 0.4 Tm) hardens nanocrystalline Ni, leading to an inverse Hall–Petch relationship. We explain this abnormal Hall–Petch effect in terms of impurity segregation to the grain boundaries of the nanocrystalline Ni

    Association of sputum and blood eosinophil concentrations with clinical measures of COPD severity: an analysis of the SPIROMICS cohort

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    Background Increased concentrations of eosinophils in blood and sputum in chronic obstructive pulmonary disease (COPD) have been associated with increased frequency of exacerbations, reduced lung function, and corticosteroid responsiveness. We aimed to assess whether high eosinophil concentrations in either sputum or blood are associated with a severe COPD phenotype, including greater exacerbation frequency, and whether blood eosinophils are predictive of sputum eosinophils. Methods We did a multicentre observational study analysing comprehensive baseline data from SPIROMICS in patients with COPD aged 40–80 years who had a smoking history of at least 20 pack-years, recruited from six clinical sites and additional subsites in the USA between Nov 12, 2010, and April 21, 2015. Inclusion criteria for this analysis were SPIROMICS baseline visit data with complete blood cell counts and, in a subset, acceptable sputum counts. We stratified patients on the basis of blood and sputum eosinophil concentrations and compared their demographic characteristics, as well as results from questionnaires, clinical assessments, and quantitative CT (QCT). We also analysed whether blood eosinophil concentrations reliably predicted sputum eosinophil concentrations. This study is registered with ClinicalTrials.gov (NCT01969344). Findings Of the 2737 patients recruited to SPIROMICS, 2499 patients were smokers and had available blood counts, and so were stratified by mean blood eosinophil count: 1262 patients with low (&lt;200 cells per μL) and 1237 with high (≥200 cells per μL) blood eosinophil counts. 827 patients were eligible for stratification by mean sputum eosinophil percentage: 656 with low (&lt;1·25%) and 171 with high (≥1·25%) sputum eosinophil percentages. The high sputum eosinophil group had significantly lower median FEV1 percentage predicted than the low sputum eosinophil group both before (65·7% [IQR 51·8–81·3] vs 75·7% [59·3–90·2], p&lt;0·0001) and after (77·3% [63·1–88·5] vs 82·9% [67·8–95·9], p=0·001) bronchodilation. QCT density measures for emphysema and air trapping were significantly higher in the high sputum eosinophil group than the low sputum eosinophil group. Exacerbations requiring corticosteroids treatment were more common in the high versus low sputum eosinophil group (p=0·002). FEV1 percentage predicted was significantly different between low and high blood eosinophil groups, but differences were less than those observed between the sputum groups. The high blood eosinophil group had slightly increased airway wall thickness (0·02 mm difference, p=0·032), higher St George Respiratory Questionnaire symptom scores (p=0·037), and increased wheezing (p=0·018), but no evidence of an association with COPD exacerbations (p=0·35) or the other indices of COPD severity, such as emphysema measured by CT density, COPD assessment test scores, Body-mass index, airflow Obstruction, Dyspnea, and Exercise index, or Global Initiative for Chronic Obstructive Lung Disease stage. Blood eosinophil counts showed a weak but significant association with sputum eosinophil counts (receiver operating characteristic area under the curve of 0·64, p&lt;0·0001), but with a high false-discovery rate of 72%. Interpretation In a large, well characterised cohort of former and current smoking patients with a broad range of COPD severity, high concentrations of sputum eosinophils were a better biomarker than high concentrations of blood eosinophils to identify a patient subgroup with more severe disease, more frequent exacerbations, and increased emphysema by QCT. Blood eosinophils alone were not a reliable biomarker for COPD severity or exacerbations, or for sputum eosinophils. Clinical trials targeting eosinophilic inflammation in COPD should consider assessing sputum eosinophils. Funding National Institutes of Health, and National Heart, Lung, and Blood Institute
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