We present an improved tropospheric nitrogen dioxide column retrieval algorithm (DOMINO v2.0) for OMI based on better air mass factors (AMFs) and a correction for across-track stripes resulting from ...calibration errors in the OMI backscattered reflectances. Since October 2004, NO2 retrievals from the Ozone Monitoring Instrument (OMI), a UV/Vis nadir spectrometer onboard NASA's EOS-Aura satellite, have been used with success in several scientific studies focusing on air quality monitoring, detection of trends, and NOx emission estimates. Dedicated evaluations of previous DOMINO tropospheric NO2 retrievals indicated their good quality, but also suggested that the tropospheric columns were susceptible to high biases (by 0-40%), probably because of errors in the air mass factor calculations. Here we update the DOMINO air mass factor approach. We calculate a new look-up table (LUT) for altitude-dependent AMFs based on more realistic atmospheric profile parameters, and include more surface albedo and surface pressure reference points than before. We improve the sampling of the TM4 model, resulting in a priori NO2 profiles that are better mixed throughout the boundary layer. We evaluate the NO2 profiles simulated with the improved TM4 sampling as used in the AMF calculations and show that they are highly consistent with in situ NO2 measurements from aircraft during the INTEX-A and INTEX-B campaigns in 2004 and 2006. Our air mass factor calculations are further updated by the implementation of a high-resolution terrain height and a high-resolution surface albedo climatology based on OMI measurements. Together with a correction for across-track stripes, the overall impact of the improved terrain height and albedo descriptions is modest (<5%) on average over large polluted areas, but still causes significant changes locally. The main changes in the DOMINO v2.0 algorithm follow from the new LUT and the improved TM4 sampling that results in more NO2 simulated aloft, where sensitivity to NO2 is higher, and amount to reductions in tropospheric NO2 columns of up to 20% in winter, and 10% in summer over extended polluted areas. We investigate the impact of aerosols on the NO2 retrieval, and based on a comparison of concurrent retrievals of clouds from OMI and aerosols from MODIS Aqua, we find empirical evidence that OMI cloud retrievals are sensitive to the presence of scattering aerosols. It follows that an implicit correction for the effects of aerosols occurs through the aerosol-induced cloud parameters in DOMINO, and we show that such an empirical correction amounts to a 20 %AMF reduction in summer and ±10% changes in winter over the eastern United States.
Combined radiochemotherapy is the currently used therapy for locally advanced pancreatic ductal adenocarcinoma (PDAC), but normal tissue toxicity limits its application. Here we test the hypothesis ...that inhibition of ATR (ATM-Rad3-related) could increase the sensitivity of the cancer cells to radiation or chemotherapy without affecting normal cells. We tested VE-822, an ATR inhibitor, for in vitro and in vivo radiosensitization. Chk1 phosphorylation was used to indicate ATR activity, γH2AX and 53BP1 foci as evidence of DNA damage and Rad51 foci for homologous recombination activity. Sensitivity to radiation (XRT) and gemcitabine was measured with clonogenic assays in vitro and tumor growth delay in vivo. Murine intestinal damage was evaluated after abdominal XRT. VE-822 inhibited ATR in vitro and in vivo. VE-822 decreased maintenance of cell-cycle checkpoints, increased persistent DNA damage and decreased homologous recombination in irradiated cancer cells. VE-822 decreased survival of pancreatic cancer cells but not normal cells in response to XRT or gemcitabine. VE-822 markedly prolonged growth delay of pancreatic cancer xenografts after XRT and gemcitabine-based chemoradiation without augmenting normal cell or tissue toxicity. These findings support ATR inhibition as a promising new approach to improve the therapeutic ration of radiochemotherapy for patients with PDAC.
The intent of this pooled analysis as part of the German society for radiation oncology (DEGRO) stereotactic body radiotherapy (SBRT) initiative was to analyze the patterns of care of SBRT for liver ...oligometastases and to derive factors influencing treated metastases control and overall survival in a large patient cohort.
From 17 German and Swiss centers, data on all patients treated for liver oligometastases with SBRT since its introduction in 1997 has been collected and entered into a centralized database. In addition to patient and tumor characteristics, data on immobilization, image guidance and motion management as well as dose prescription and fractionation has been gathered. Besides dose response and survival statistics, time trends of the aforementioned variables have been investigated.
In total, 474 patients with 623 liver oligometastases (median 1 lesion/patient; range 1–4) have been collected from 1997 until 2015. Predominant histologies were colorectal cancer (n = 213 pts.; 300 lesions) and breast cancer (n = 57; 81 lesions). All centers employed an SBRT specific setup. Initially, stereotactic coordinates and CT simulation were used for treatment set-up (55%), but eventually were replaced by CBCT guidance (28%) or more recently robotic tracking (17%). High variance in fraction (fx) number (median 1 fx; range 1–13) and dose per fraction (median: 18.5 Gy; range 3–37.5 Gy) was observed, although median BED remained consistently high after an initial learning curve. Median follow-up time was 15 months; median overall survival after SBRT was 24 months. One- and 2-year treated metastases control rate of treated lesions was 77% and 64%; if maximum isocenter biological equivalent dose (BED) was greater than 150 Gy EQD2Gy, it increased to 83% and 70%, respectively. Besides radiation dose colorectal and breast histology and motion management methods were associated with improved treated metastases control.
After an initial learning curve with regards to total cumulative doses, consistently high biologically effective doses have been employed translating into high local tumor control at 1 and 2 years. The true impact of histology and motion management method on treated metastases control deserve deeper analysis. Overall survival is mainly influenced by histology and metastatic tumor burden.
We combine the quasi-stellar object (QSO) samples from the 2dF QSO Redshift Survey (2QZ) and the 2dF-Sloan Digital Sky Survey luminous red galaxy (LRG) and QSO Survey (2dF-SDSS LRG and QSO, hereafter ...2SLAQ) in order to investigate the clustering of z∼ 1.5 QSOs and measure the correlation function (ξ). The clustering signal in redshift-space and projected along the sky direction is similar to that previously obtained from the 2QZ sample alone. By fitting functional forms for ξ(σ, π), the correlation function measured along and across the line of sight, we find, as expected, that β, the dynamical infall parameter and Ω0
m, the cosmological density parameter, are degenerate. However, this degeneracy can be lifted by using linear theory predictions under different cosmological scenarios. Using the combination of the 2QZ and 2SLAQ QSO data, we obtain: βQSO(z= 1.5) = 0.60+0.14
−0.11, Ω0
m= 0.25+0.09
−0.07 which imply a value for the QSO bias, b(z= 1.4) = 1.5 ± 0.2.
The combination of the 2QZ with the fainter 2SLAQ QSO sample further reveals that QSO clustering does not depend strongly on luminosity at fixed redshift. This result is inconsistent with the expectation of simple 'high peaks' biasing models where more luminous, rare QSOs are assumed to inhabit higher mass haloes. The data are more consistent with models which predict that QSOs of different luminosities reside in haloes of similar mass. By assuming ellipsoidal models for the collapse of density perturbations, we estimate the mass of the dark matter haloes which the QSOs inhabit as ∼3 × 1012
h
−1M⊙. We find that this halo mass does not evolve strongly with redshift nor depend on QSO luminosity. Assuming a range of relations which relate halo to black hole mass, we investigate how black hole mass correlates with luminosity and redshift, and ascertain the relation between Eddington efficiency and black hole mass. Our results suggest that QSOs of different luminosities may contain black holes of similar mass.
Somatic mutations accumulate in healthy tissues as we age, giving rise to cancer and potentially contributing to ageing. To study somatic mutations in non-neoplastic tissues, we developed a series of ...protocols to sequence the genomes of small populations of cells isolated from histological sections. Here, we describe a complete workflow that combines laser-capture microdissection (LCM) with low-input genome sequencing, while circumventing the use of whole-genome amplification (WGA). The protocol is subdivided broadly into four steps: tissue processing, LCM, low-input library generation and mutation calling and filtering. The tissue processing and LCM steps are provided as general guidelines that might require tailoring based on the specific requirements of the study at hand. Our protocol for low-input library generation uses enzymatic rather than acoustic fragmentation to generate WGA-free whole-genome libraries. Finally, the mutation calling and filtering strategy has been adapted from previously published protocols to account for artifacts introduced via library creation. To date, we have used this workflow to perform targeted and whole-genome sequencing of small populations of cells (typically 100-1,000 cells) in thousands of microbiopsies from a wide range of human tissues. The low-input DNA protocol is designed to be compatible with liquid handling platforms and make use of equipment and expertise standard to any core sequencing facility. However, obtaining low-input DNA material via LCM requires specialized equipment and expertise. The entire protocol from tissue reception through whole-genome library generation can be accomplished in as little as 1 week, although 2-3 weeks would be a more typical turnaround time.
We present the galaxy two-point angular correlation function for galaxies selected from the seventh data release of the Sloan Digital Sky Survey (SDSS). The galaxy sample was selected with r-band ...apparent magnitudes between 17 and 21, and we measure the correlation function for the full sample as well as for the four magnitude ranges: 17-18, 18-19, 19-20 and 20-21. We update the flag criteria to select a clean galaxy catalogue and detail specific tests that we perform to characterize systematic effects, including the effects of seeing, Galactic extinction and the overall survey uniformity. Notably, we find that optimally we can use observed regions with seeing <1.5 arcsec, and r-band extinction <0.13 mag, smaller than previously published results. Furthermore, we confirm that the uniformity of the SDSS photometry is minimally affected by the stripe geometry. We find that, overall, the two-point angular correlation function can be described by a power law, ω(θ) = A
ωθ(1 − γ) with γ 1.72, over the range 0
005-10°. We also find similar relationships for the four magnitude subsamples, but the amplitude within the same angular interval for the four subsamples is found to decrease with fainter magnitudes, in agreement with previous results. We find that the systematic signals are well below the galaxy angular correlation function for angles less than approximately 5°, which limits the modelling of galaxy angular correlations on larger scales. Finally, we present our custom, highly parallelized two-point correlation code that we used in this analysis.
The causes of metabolic syndrome (MS), which may be a precursor of coronary disease, are uncertain. We hypothesize that disturbances in neuroendocrine and cardiac autonomic activity (CAA) contribute ...to development of MS. We examine reversibility and the power of psychosocial and behavioral factors to explain the neuroendocrine adaptations that accompany MS.
This was a double-blind case-control study of working men aged 45 to 63 years drawn from the Whitehall II cohort. MS cases (n=30) were compared with healthy controls (n=153). Cortisol secretion, sensitivity, and 24-hour cortisol metabolite and catecholamine output were measured over 2 days. CAA was obtained from power spectral analysis of heart rate variability (HRV) recordings. Twenty-four-hour cortisol metabolite and normetanephrine (3-methoxynorepinephrine) outputs were higher among cases than controls (+ 0.49, +0.45 SD, respectively). HRV and total power were lower among cases (both -0.72 SD). Serum interleukin-6, plasma C-reactive protein, and viscosity were higher among cases (+0.89, +0.51, and +0.72 SD). Lower HRV was associated with higher normetanephrine output (r=-0.19; P=0.03). Among former cases (MS 5 years previously, n=23), cortisol output, heart rate, and interleukin-6 were at the level of controls. Psychosocial factors accounted for 37% of the link between MS and normetanephrine output, and 7% to 19% for CAA. Health-related behaviors accounted for 5% to 18% of neuroendocrine differences.
Neuroendocrine stress axes are activated in MS. There is relative cardiac sympathetic predominance. The neuroendocrine changes may be reversible. This case-control study provides the first evidence that chronic stress may be a cause of MS. Confirmatory prospective studies are required.
Background: CHARGE syndrome is a non-random clustering of congenital anomalies including coloboma, heart defects, choanal atresia, retarded growth and development, genital hypoplasia, ear anomalies, ...and deafness. A consistent feature in CHARGE syndrome is semicircular canal hypoplasia resulting in vestibular areflexia. Other commonly associated congenital anomalies are facial nerve palsy, cleft lip/palate, and tracheo-oesophageal fistula. Specific behavioural problems, including autistic-like behaviour, have been described. The CHD7 gene on chromosome 8q12.1 was recently discovered as a major gene involved in the aetiology of this syndrome. Methods: The coding regions of CHD7 were screened for mutations in 107 index patients with clinical features suggestive of CHARGE syndrome. Clinical data of the mutation positive patients were sampled to study the phenotypic spectrum of mutations in the CHD7 gene. Results: Mutations were identified in 69 patients. Here we describe the clinical features of 47 of these patients, including two sib pairs. Most mutations were unique and were scattered throughout the gene. All patients but one fulfilled the current diagnostic criteria for CHARGE syndrome. No genotype-phenotype correlations were apparent in this cohort, which is best demonstrated by the differences in clinical presentation in sib pairs with identical mutations. Somatic mosaicism was detected in the unaffected mother of a sib pair, supporting the existence of germline mosaicism. Conclusions:CHD7 mutations account for the majority of the cases with CHARGE syndrome, with a broad clinical variability and without an obvious genotype-phenotype correlation. In one case evidence for germline mosaicism was provided.
Pathogens secrete effector proteins to interfere with plant innate immunity, in which Ca2+/calmodulin (CaM) signalling plays key roles. Thus far, few effectors have been identified that directly ...interact with CaM for defence suppression. Here, we report that SFI5, an RXLR effector from Phytophthora infestans, suppresses microbe-associated molecular pattern (MAMP)-triggered immunity (MTI) by interacting with host CaMs.
We predicted the CaM-binding site in SFI5 using in silico analysis. The interaction between SFI5 and CaM was tested by both in vitro and in vivo assays. MTI suppression by SFI5 and truncated variants were performed in a tomato protoplast system.
We found that both the predicted CaM-binding site and the full-length SFI5 protein interact with CaM in the presence of Ca2+. MTI responses, such as FRK1 upregulation, reactive oxygen species accumulation, and mitogen-activated protein kinase activation were suppressed by truncated SFI5 proteins containing the C-terminal CaM-binding site but not by those without it. The plasma membrane localization of SFI5 and its ability to enhance infection were also perturbed by loss of the CaM-binding site.
We conclude that CaM-binding is required for localization and activity of SFI5. We propose that SFI5 suppresses plant immunity by interfering with immune signalling components after activation by CaMs.
Novel methods of data analysis were used to interpret codling moth (Cydia pomonella) catch data from central-trap, multiple-release experiments using a standard codlemone-baited monitoring trap in ...commercial apple orchards not under mating disruption. The main objectives were to determine consistency and reliability for measures of: 1) the trapping radius, composed of the trap's behaviorally effective plume reach and the maximum dispersive distance of a responder population; and 2) the proportion of the population present in the trapping area that is caught. Two moth release designs were used: 1) moth releases at regular intervals in the four cardinal directions, and 2) evenly distributed moth releases across entire approximately 18-ha orchard blocks using both high and low codling moth populations. For both release designs, at high populations, the mean proportion catch was 0.01, and for the even release of low populations, that value was approximately 0.02. Mean maximum dispersive distance for released codling moth males was approximately 260 m. Behaviorally effective plume reach for the standard codling moth trap was < 5 m, and total trapping area for a single trap was approximately 21 ha. These estimates were consistent across three growing seasons and are supported by extraordinarily high replication for this type of field experiment. Knowing the trapping area and mean proportion caught, catch number per single monitoring trap can be translated into absolute pest density using the equation: males per trapping area = catch per trapping area/proportion caught. Thus, catches of 1, 3, 10, and 30 codling moth males per trap translate to approximately 5, 14, 48, and 143 males/ha, respectively, and reflect equal densities of females, because the codling moth sex ratio is 1:1. Combined with life-table data on codling moth fecundity and mortality, along with data on crop yield per trapping area, this fundamental knowledge of how to interpret catch numbers will enable pest managers to make considerably more precise projections of damage and therefore more precise and reliable decisions on whether insecticide applications are justified. The principles and methods established here for estimating absolute codling moth density may be broadly applicable to pests generally and thereby could set a new standard for integrated pest management decisions based on trapping.
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