ABSTRACT
We searched for an isotropic stochastic gravitational wave background in the second data release of the International Pulsar Timing Array, a global collaboration synthesizing decadal-length ...pulsar-timing campaigns in North America, Europe, and Australia. In our reference search for a power-law strain spectrum of the form $h_c = A(f/1\, \mathrm{yr}^{-1})^{\alpha }$, we found strong evidence for a spectrally similar low-frequency stochastic process of amplitude $A = 3.8^{+6.3}_{-2.5}\times 10^{-15}$ and spectral index α = −0.5 ± 0.5, where the uncertainties represent 95 per cent credible regions, using information from the auto- and cross-correlation terms between the pulsars in the array. For a spectral index of α = −2/3, as expected from a population of inspiralling supermassive black hole binaries, the recovered amplitude is $A = 2.8^{+1.2}_{-0.8}\times 10^{-15}$. None the less, no significant evidence of the Hellings–Downs correlations that would indicate a gravitational-wave origin was found. We also analysed the constituent data from the individual pulsar timing arrays in a consistent way, and clearly demonstrate that the combined international data set is more sensitive. Furthermore, we demonstrate that this combined data set produces comparable constraints to recent single-array data sets which have more data than the constituent parts of the combination. Future international data releases will deliver increased sensitivity to gravitational wave radiation, and significantly increase the detection probability.
ABSTRACT
The International Pulsar Timing Array 2nd data release is the combination of data sets from worldwide collaborations. In this study, we search for continuous waves: gravitational wave ...signals produced by individual supermassive black hole binaries in the local universe. We consider binaries on circular orbits and neglect the evolution of orbital frequency over the observational span. We find no evidence for such signals and set sky averaged 95 per cent upper limits on their amplitude h95. The most sensitive frequency is 10 nHz with h95 = 9.1 × 10−15. We achieved the best upper limit to date at low and high frequencies of the PTA band thanks to improved effective cadence of observations. In our analysis, we have taken into account the recently discovered common red noise process, which has an impact at low frequencies. We also find that the peculiar noise features present in some pulsars data must be taken into account to reduce the false alarm. We show that using custom noise models is essential in searching for continuous gravitational wave signals and setting the upper limit.
The majority of insecticidescurrently in use are organophosphorus, carbamate, and synthetic pyrethroid compounds. Organophosphorus insecticides (OPs) produce toxicity by inhibiting the cholinesterase ...enzymes in the nervous system. Monitoring of acetylcholinesterase (AChE) inhibition has been widely used in terrestrial and freshwater aquatic systems as an indicator of OP exposure and effects. This review describes the use of AChE inhibition as a biomarker in the estuarine environment, discusses the relationship between AChE inhibition and other manifestations of OP toxicity, and highlights areas where additional research is needed. A variety of studies with estuarine fish have suggested that brain AChE inhibition levels of >70% are associated with mortality in most species. Selected species, however, appear capable of tolerating much higher levels (>90%) of brain inhibition. Sublethal effects on stamina have been reported for some estuarine fish in association with brain AChE inhibition levels as low as 50%. Most studies suggest, however, that these effects are observed only when brain AChE inhibition is at near‐lethal levels. A number of field studies have successfully used AChE inhibition in fish as a biomarker in the estuarine environment. The use of AChE inhibition as a biomarker in estuarine invertebrates has been less well studied. Although AChE inhibition has been measured in the tissues of a variety of invertebrate species following OP exposure, the relationship between AChE inhibition and lethality is less distinct. Additional work is needed in both fish and invertebrates to better explain species‐specific differences in the relationship between AChE inhibition and mortality and to investigate other physiological perturbations associated with AChE inhibition.
Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent ...research, and proposes strategies for translating solutions into practice.
More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account.
The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working.
With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years.
Chemical dispersants can be a useful tool to mitigate oil spills. This study examined potential risks to sensitive estuarine species by comparing the toxicity of two dispersants (Corexit
®
EC9500A ...and Finasol
®
OSR 52) individually and in chemically enhanced water-accommodated fractions (CEWAFs) of Louisiana Sweet Crude oil. Acute toxicity thresholds and sublethal biomarker responses were determined in seven species (sheepshead minnow, grass shrimp, mysid, amphipod, polychaete, hard clam, mud snail). Comparing median lethal (LC
50
) values for the dispersants, Finasol was generally more toxic than Corexit and had greater sublethal toxicity (impaired embryonic hatching, increased lipid peroxidation, decreased acetylcholinesterase activity). The nominal concentration-based mean LC
50
for all species tested with Corexit was 150.31 mg/L compared with 43.27 mg/L with Finasol. Comparing the toxicity of the CEWAFs using the nominal concentrations (% CEWAF), Corexit-CEWAFs appeared more toxic than Finasol-CEWAFs; however, when LC
50
values were calculated using measured hydrocarbon concentrations, the Finasol-CEWAFs were more toxic. There was greater dispersion efficiency leading to greater hydrocarbon concentrations measured in the Corexit-CEWAF solutions than in equivalent Finasol-CEWAF solutions. The measured concentration-based mean LC
50
values for all species tested with Corexit-CEWAF were 261.96 mg/L total extractable hydrocarbons (TEH) and 2.95 mg/L total polycyclic aromatic hydrocarbons (PAH), whereas the mean LC
50
values for all species tested with Finasol-CEWAF were 23.19 mg/L TEH and 0.49 mg/L total PAH. Larval life stages were generally more sensitive to dispersants and dispersed oil than adult life stages within a species. These results will help to inform management decisions regarding the use of oil-spill dispersants.
The availability of both the mouse and human genome sequences allows for the systematic discovery of human gene function through the use of the mouse as a model system. To accelerate the genetic ...determination of gene function, we have developed a sequence-tagged gene-trap library of >270,000 mouse embryonic stem cell clones representing mutations in ≈60% of mammalian genes. Through the generation and phenotypic analysis of knockout mice from this resource, we are undertaking a functional screen to identify genes regulating physiological parameters such as blood pressure. As part of this screen, mice deficient for the Wnk1 kinase gene were generated and analyzed. Genetic studies in humans have shown that large intronic deletions in WNK1 lead to its overexpression and are responsible for pseudohypoaldosteronism type II, an autosomal dominant disorder characterized by hypertension, increased renal salt reabsorption, and impaired K+and H+excretion. Consistent with the human genetic studies, Wnk1 heterozygous mice displayed a significant decrease in blood pressure. Mice homozygous for the Wnk1 mutation died during embryonic development before day 13 of gestation. These results demonstrate that Wnk1 is a regulator of blood pressure critical for development and illustrate the utility of a functional screen driven by a sequence-based mutagenesis approach.
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Larval oysters are sensitive to thin oil sheens at environmentally relevant concentrations of PAHs.
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Oil sheen toxicity increases with UV light exposure.
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Short term exposure led to latent ...effects on oyster survival and swimming ability.
The Eastern oyster (
Crassostrea virginica)
is an important commercial bivalve species which also has numerous ecological roles including biogeochemical cycling, providing habitat for larval fish and crustaceans, and reducing the impacts of coastal storms. Oil may pose a threat to oyster larvae swimming in the water column, leading to potential negative effects on survival, growth, and development. Oil toxicity may be further enhanced by chemical changes in the presence of sunlight. This study determined the toxicity of thin oil sheens with and without ultraviolet (UV) light, then examined the latent effects of the short term exposure on longer term survival and swimming ability. Larval
C. virginica
were exposed to four different oil sheen thicknesses for 24 h with either no UV light or 2-h UV light. Following the exposure, larvae were transferred to clean seawater and no UV light for 96 h. The presence of a 2-h UV light exposure significantly increased oyster mortality, indicating photo-enhanced toxicity. The LC
50
for a 24-h oil sheen exposure without UV was 7.26 µm (23 µg/L PAH
50
) while a 2 h-UV exposure lowered the sheen toxicity threshold to 2.67 µm (10 µg/L PAH
50
). A previous 24-h oil sheen exposure (≥0.5 µm) led to latent effects on larval oyster survival, regardless of previous UV exposure. Sublethal impacts to larval oyster swimming behavior were also observed from the previous oil sheen exposure combined with UV exposure. This study provides new data for the toxicity of thin oil sheens to a sensitive early life stage of estuarine bivalve.
A computational fluid dynamics(CFD) simulation was carried out to study on flow field characteristics in dual-Rusthton turbine stirred vessels in laminar and turbulent regimes. Model validation was ...conducted using experimental data in the literature. The simulation results show that flow pattern and dimensionless velocity distribution vary with Reynolds number in laminar regime, while these parameters remain almost unchanged for different Reynolds numbers in turbulent regime. For vessels with a certain geometrical configuration, flow pattern, dimensionless velocity distribution and impeller power number depend mainly on Reynolds number, and are little affected by working medium and enlargement scale. By changing impeller spacing and off-bottom clearance of lower impeller, it is obtained the parallel, merging and diverging flow patterns in turbulent regime, and the changing processes of flow patterns in laminar regime for the three configurations. Total power number has the order of parallel>diverging>merging for the three configurations at the same Reynolds number. With increasing of Reynolds number, the power number of merging configuration shows the largest drop, followed by diverging configuration, and the lowest drop for parallel configuration in laminar regime, while power number rises slightly for the three configurations in turbulent regime.
We interviewed 328 men diagnosed with prostate cancer before the age of 75 years and 328 age-matched population controls. The principal hypotheses were that risk would increase with a high intake of ...total or saturated fat and would decrease with a high intake of carotene (beta-carotene equivalents) or lycopene. We also examined the associations of other nutrients and foods with risk. There was no evidence for an association between fat intake and risk, although the average fat intake was high and the range of fat intakes was narrow (medians of lower and upper thirds of percentage of energy from fat among controls were 34.3% and 42.9% respectively). Risk was lower in subjects with higher carotene intake: odds ratios 0.65 (95% CI 0.45-0.94) and 0.76 (0.53-1.10) in the middle and upper thirds of carotene intake respectively (P for trend = 0.150). Lycopene was not associated with risk. Among 13 other nutrients examined, the odds ratios in the top third of intake were below 0.8 for: potassium, 0.74 (0.51-1.09; P for trend = 0.054); zinc, 0.73 (0.49-1.08; P for trend = 0.126); iodine, 0.75 (0.51-1.11; P for trend = 0.077); vitamin B6 food only, 0.77 (0.53-1.12; P for trend = 0.077); and vitamin B6 including supplements, 0.70 (0.48-1.03; P for trend = 0.029). Among 18 foods examined, statistically significant associations were observed for: garlic as food, > or = 2/week vs never, 0.56 (0.33-0.93); garlic including supplements, > or = 2/week vs never, 0.60 (0.37-0.96); baked beans, > or = 2/week vs < 1/month, 0.57 (0.34-0.95); and garden peas, > or = 5/week vs < or = 3/month, 0.35 (0.13-0.91). This study does not support the hypothesis that fat increases risk and is equivocal in relation to carotene. The possible relationships of vitamin B6, garlic, beans and peas with risk for prostate cancer should be further investigated.
Mosquito control insecticide use in the coastal zone coincides with the habitat and mariculture operations of commercially and ecologically important shellfish species. Few data are available ...regarding insecticide toxicity to shellfish early life stages, and potential interactions with abiotic stressors, such as low oxygen and increased CO
2
(low pH), are less understood. Toxicity was assessed at 4 and 21 days for larval and juvenile stages of the Eastern oyster,
Crassostrea virginica
, and the hard clam,
Mercenaria mercenaria
, using two pyrethroids (resmethrin and permethrin), an organophosphate (naled), and a juvenile growth hormone mimic (methoprene). Acute toxicity (4-day LC
50
) values ranged from 1.59 to >10 mg/L. Overall, clams were more susceptible to mosquito control insecticides than oysters. Naled was the most toxic compound in oyster larvae, whereas resmethrin was the most toxic compound in clam larvae. Mortality for both species generally increased with chronic insecticide exposure (21-day LC
50
values ranged from 0.60 to 9.49 mg/L). Insecticide exposure also caused sublethal effects, including decreased swimming activity after 4 days in larval oysters (4-day EC
50
values of 0.60 to 2.33 mg/L) and decreased growth (shell area and weight) in juvenile clams and oysters after 21 days (detected at concentrations ranging from 0.625 to 10 mg/L). Hypoxia, hypercapnia, and a combination of hypoxia and hypercapnia caused mortality in larval clams and increased resmethrin toxicity. These data will benefit both shellfish mariculture operations and environmental resource agencies as they manage the use of mosquito control insecticides near coastal ecosystems.
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