3,364 research outputs found
Negative Differential Resistivity and Positive Temperature Coefficient of Resistivity effect in the diffusion limited current of ferroelectric thin film capacitors
We present a model for the leakage current in ferroelectric thin- film
capacitors which explains two of the observed phenomena that have escaped
satisfactory explanation, i.e. the occurrence of either a plateau or negative
differential resistivity at low voltages, and the observation of a Positive
Temperature Coefficient of Resistivity (PTCR) effect in certain samples in the
high-voltage regime. The leakage current is modelled by considering a
diffusion-limited current process, which in the high-voltage regime recovers
the diffusion-limited Schottky relationship of Simmons already shown to be
applicable in these systems
Cost Effectiveness Analysis Evaluating Real-Time Characterization of Diminutive Colorectal Polyp Histology using Narrow Band Imaging (NBI)
Background: Endoscopists and new computer-aided programs can achieve performance benchmarks for real-time diagnosis of colorectal polyps using Narrow-Band Imaging (NBI), though do not perform as well as endoscopists with expertise in advanced imaging. Previous cost-effectiveness studies on optical diagnosis have focused on expert performance, potentially over-estimating its benefits.
Aim: Determine cost-effectiveness of an NBI ‘characterize, resect and discard (CRD)’ strategy using updated assumptions based on non-expert performance.
Methods: Markov model was constructed to compare cost-effectiveness of the CRD strategy, where diminutive polyps characterized as non-adenomas with high confidence are not resected and adenomas are resected and discarded, versus standard of care (SOC) in which all polyps are resected with histologic analysis. Rates related to NBI performance, missed polyps, polyp progression, malignancy, and complications, as well as quality-adjusted life years (QALYs) were derived from the literature. Costs were age and insurer-specific. Mean QALYs and costs were calculated using first order Monte Carlo simulation. Deterministic and probabilistic sensitivity analyses were conducted.
Results: The mean QALY estimates were similar for the CRD (8.563, 95% CI: 8.557-8.571) and SOC strategy (8.563, 8.557-8.571), but costs were reduced (2,800.27, mean incremental cost savings: 708 million to $1.06 billion annually. The model was sensitive to the incidence of tubular adenomas; the results were otherwise robust in all other one-way and probabilistic analyses.
Conclusions: An NBI CRD strategy is cost-effective when compared to the SOC, even when employed by non-experts. The appreciated benefit is primarily due to cost savings of the CRD strategy
The first super-Earth Detection from the High Cadence and High Radial Velocity Precision Dharma Planet Survey
The Dharma Planet Survey (DPS) aims to monitor about 150 nearby very bright
FGKM dwarfs (within 50 pc) during 20162020 for low-mass planet detection and
characterization using the TOU very high resolution optical spectrograph
(R100,000, 380-900nm). TOU was initially mounted to the 2-m Automatic
Spectroscopic Telescope at Fairborn Observatory in 2013-2015 to conduct a pilot
survey, then moved to the dedicated 50-inch automatic telescope on Mt. Lemmon
in 2016 to launch the survey. Here we report the first planet detection from
DPS, a super-Earth candidate orbiting a bright K dwarf star, HD 26965. It is
the second brightest star ( mag) on the sky with a super-Earth
candidate. The planet candidate has a mass of 8.47,
period of d, and eccentricity of . This RV
signal was independently detected by Diaz et al. (2018), but they could not
confirm if the signal is from a planet or from stellar activity. The orbital
period of the planet is close to the rotation period of the star (3944.5 d)
measured from stellar activity indicators. Our high precision photometric
campaign and line bisector analysis of this star do not find any significant
variations at the orbital period. Stellar RV jitters modeled from star spots
and convection inhibition are also not strong enough to explain the RV signal
detected. After further comparing RV data from the star's active magnetic phase
and quiet magnetic phase, we conclude that the RV signal is due to
planetary-reflex motion and not stellar activity.Comment: 13 pages, 17 figures, Accepted for publication in MNRA
A Brief History of AGN
Astronomers knew early in the twentieth century that some galaxies have
emission-line nuclei. However, even the systematic study by Seyfert (1943) was
not enough to launch active galactic nuclei (AGN) as a major topic of
astronomy. The advances in radio astronomy in the 1950s revealed a new universe
of energetic phenomena, and inevitably led to the discovery of quasars. These
discoveries demanded the attention of observers and theorists, and AGN have
been a subject of intense effort ever since. Only a year after the recognition
of the redshifts of 3C 273 and 3C 48 in 1963, the idea of energy production by
accretion onto a black hole was advanced. However, acceptance of this idea came
slowly, encouraged by the discovery of black hole X-ray sources in our Galaxy
and, more recently, supermassive black holes in the center of the Milky Way and
other galaxies. Many questions remain as to the formation and fueling of the
hole, the geometry of the central regions, the detailed emission mechanisms,
the production of jets, and other aspects. The study of AGN will remain a
vigorous part of astronomy for the foreseeable future.Comment: 37 pages, no figures. Uses aaspp4.sty. To be published in
Publications of the Astronomical Society of the Pacific, 1999 Jun
DHODH modulates transcriptional elongation in the neural crest and melanoma
Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation
The Evolution of the Anopheles 16 Genomes Project
We report the imminent completion of a set of reference genome assemblies for 16 species of Anopheles mosquitoes. In addition to providing a generally useful resource for comparative genomic analyses, these genome sequences will greatly facilitate exploration of the capacity exhibited by some Anopheline mosquito species to serve as vectors for malaria parasites. A community analysis project will commence soon to perform a thorough comparative genomic investigation of these newly sequenced genomes. Completion of this project via the use of short next-generation sequence reads required innovation in both the bioinformatic and laboratory realms, and the resulting knowledge gained could prove useful for genome sequencing projects targeting other unconventional genomes
Crizotinib-Resistant Mutants of EML4-ALK Identified Through an Accelerated Mutagenesis Screen
Activating gene rearrangements of anaplastic lymphoma kinase (ALK) have been identified as driver mutations in non-small-cell lung cancer, inflammatory myofibroblastic tumors, and other cancers. Crizotinib, a dual MET/ALK inhibitor, has demonstrated promising clinical activity in patients with non-small-cell lung cancer and inflammatory myofibroblastic tumors harboring ALK translocations. Inhibitors of driver kinases often elicit kinase domain mutations that confer resistance, and such mutations have been successfully predicted using in vitro mutagenesis screens. Here, this approach was used to discover an extensive set of ALK mutations that can confer resistance to crizotinib. Mutations at 16 residues were identified, structurally clustered into five regions around the kinase active site, which conferred varying degrees of resistance. The screen successfully predicted the L1196M, C1156Y, and F1174L mutations, recently identified in crizotinib-resistant patients. In separate studies, we demonstrated that crizotinib has relatively modest potency in ALK-positive non-small-cell lung cancer cell lines. A more potent ALK inhibitor, TAE684, maintained substantial activity against mutations that conferred resistance to crizotinib. Our study identifies multiple novel mutations in ALK that may confer clinical resistance to crizotinib, suggests that crizotinib's narrow selectivity window may underlie its susceptibility to such resistance and demonstrates that a more potent ALK inhibitor may be effective at overcoming resistance
Changing gender roles and attitudes and their implications for well-being around the new millennium
<b>Purpose</b><p></p>
Given evidence that gender role attitudes (GRAs) and actual gender roles impact on well-being, we examine associations between GRAs, three roles (marital status, household chore division, couple employment) and psychological distress in working-age men and women. We investigate time-trends reflecting broader social and economic changes, by focusing on three age groups at two dates.<p></p>
<b>Methods</b><p></p>
We used British Household Panel Survey data from 20- to 64-year-olds in heterosexual couple households in 1991 (N = 5,302) and 2007 (N = 6,621). We examined: levels of traditional GRAs according to gender, age, date, household and employment roles; associations which GRAs and roles had with psychological distress (measured via the GHQ-12); whether psychological distress increased when GRAs conflicted with actual roles; and whether any of these associations differed according to gender, age or date.<p></p>
<b>Results</b><p></p>
Gender traditionalism was lower among women, younger people, those participating in 2007 and in ‘less traditional’ relationships and households. Psychological distress was higher among those with more traditional GRAs and, particularly among men, for those not employed, and there was some evidence of different patterns of association according to age-group. There was limited evidence, among women only, of increased psychological distress when GRAs and actual roles conflicted and/or reductions when GRAs and roles agreed, particularly in respect of household chores and paid employment.<p></p>
<b>Conclusions</b><p></p>
Although some aspects of gender roles and attitudes (traditionalism and paid employment) are associated with well-being, others (marital status and household chores), and attitude-role consistency, may have little impact on the well-being of contemporary UK adults.<p></p>
Density‑dependent winter survival of immatures in an irruptive raptor with pulsed breeding
Highly mobile predators can show strong numerical responses to pulsed resources, sometimes resulting in irruptions where large numbers of young invade landscapes at a continental scale. High production of young in irruption years may have a strong influence on the population dynamics unless immature survival is reduced compared to non-irruption years. This could occur if subordinate individuals (mainly immatures) are forced into suboptimal habitats due to density-dependent effects in irruption years. To test whether irruptive individuals had lower survival than non-irruptive ones, we combined necropsy results (N = 365) with telemetry (N = 185) from more than 20 years to record timing and causes of mortality in snowy owls (Bubo scandiacus), which irrupt into eastern North America during winter following high breeding output caused by lemming peaks in the Arctic. Mortality was more than four times higher in irruption years than non-irruption years, but only for immatures, and occurred disproportionately in early winter for immatures, but not adults. Mortality was also higher in eastern North America, where owl abundance fluctuates considerably between years, compared to core winter regions of the Arctic and Prairies where populations are more stable. Most mortality was not due to starvation, but rather associated with human activity, especially vehicle collisions. We conclude that immature snowy owls that irrupt into eastern North America are limited by density-dependent factors, such as increased competition forcing individuals to occupy risky human-altered habitats. For highly mobile, irruptive animals, resource pulses may have a limited impact on population dynamics due to low subsequent survival of breeding output during the nonbreeding season.publishedVersio
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