Exploring a search for long-duration transient gravitational waves associated with magnetar bursts

Soft gamma repeaters and anomalous X-ray pulsars are thought to be magnetars, neutron stars with strong magnetic fields of order $\mathord{\sim} 10^{13}$--$10^{15} \, \mathrm{gauss}$. These objects emit intermittent bursts of hard X-rays and soft gamma rays. Quasiperiodic oscillations in the X-ray tails of giant flares imply the existence of neutron star oscillation modes which could emit gravitational waves powered by the magnetar's magnetic energy reservoir. We describe a method to search for transient gravitational-wave signals associated with magnetar bursts with durations of 10s to 1000s of seconds. The sensitivity of this method is estimated by adding simulated waveforms to data from the sixth science run of Laser Interferometer Gravitational-wave Observatory (LIGO). We find a search sensitivity in terms of the root sum square strain amplitude of $h_{\mathrm{rss}} = 1.3 \times 10^{-21} \, \mathrm{Hz}^{-1/2}$ for a half sine-Gaussian waveform with a central frequency $f_0 = 150 \, \mathrm{Hz}$ and a characteristic time $\tau = 400 \, \mathrm{s}$. This corresponds to a gravitational wave energy of $E_{\mathrm{GW}} = 4.3 \times 10^{46} \, \mathrm{erg}$, the same order of magnitude as the 2004 giant flare which had an estimated electromagnetic energy of $E_{\mathrm{EM}} = \mathord{\sim} 1.7 \times 10^{46} (d/ 8.7 \, \mathrm{kpc})^2 \, \mathrm{erg}$, where $d$ is the distance to SGR 1806-20. We present an extrapolation of these results to Advanced LIGO, estimating a sensitivity to a gravitational wave energy of $E_{\mathrm{GW}} = 3.2 \times 10^{43} \, \mathrm{erg}$ for a magnetar at a distance of $1.6 \, \mathrm{kpc}$. These results suggest this search method can probe significantly below the energy budgets for magnetar burst emission mechanisms such as crust cracking and hydrodynamic deformation

Genomic Assessment of Blood-Derived Circulating Tumor DNA in Patients With Colorectal Cancers: Correlation With Tissue Sequencing, Therapeutic Response, and Survival.

PurposeGenomic alterations in blood-derived circulating tumor DNA (ctDNA) from patients with colorectal cancers were correlated with clinical outcomes.Patients and methodsNext-generation sequencing of ctDNA (54- to 73-gene panel) was performed in 94 patients with colorectal cancer.ResultsMost patients (96%) had metastatic or recurrent disease at the time of blood draw. The median number of nonsynonymous alterations per patient was three (range, zero to 30). The most frequently aberrant genes were TP53 (52.1% of patients), KRAS (34%), and APC (28.7%). Concordance between tissue and blood next-generation sequencing ranged from 63.2% (APC) to 85.5% (BRAF). Altogether, 74 patients (79%) had one or more nonsynonymous alterations, 69 (73%) had one or more potentially actionable alterations, and 61 (65%) had an alteration actionable by a drug approved by the US Food and Drug Administration (on or off label). Lung metastases correlated with improved survival from diagnosis in univariable analysis. ctDNA of 5% or more from blood tests as well as EGFR and ERBB2 (HER2) nonsynonymous alterations correlated with worse survival (but only ERBB2 remained significant in multivariable analysis). No two patients had identical molecular portfolios. Overall, 65% versus 31% of patients treated with matched (n = 17) versus unmatched therapy (n = 18) after ctDNA testing achieved stable disease for 6 months or more, partial response, or complete response (P = .045); progression-free survival, 6.1 versus 2.3 months (P = .08); and survival not reached versus 9.4 months (P = .146; all by multivariable analysis).ConclusionPatients with colorectal cancer have heterogeneous ctDNA profiles, and most harbor potentially actionable ctDNA alterations. Matched therapy yielded higher rates of stable disease for 6 months or more, partial response, or complete response. ctDNA assessment may have clinical utility and merits further investigation

Sealing in Turbomachinery

Clearance control is of paramount importance to turbomachinery designers and is required to meet today's aggressive power output, efficiency, and operational life goals. Excessive clearances lead to losses in cycle efficiency, flow instabilities, and hot gas ingestion into disk cavities. Insufficient clearances limit coolant flows and cause interface rubbing, overheating downstream components and damaging interfaces, thus limiting component life. Designers have put renewed attention on clearance control, as it is often the most cost effective method to enhance system performance. Advanced concepts and proper material selection continue to play important roles in maintaining interface clearances to enable the system to meet design goals. This work presents an overview of turbomachinery sealing to control clearances. Areas covered include: characteristics of gas and steam turbine sealing applications and environments, benefits of sealing, types of standard static and dynamics seals, advanced seal designs, as well as life and limitations issues

Revisiting Epidermal Growth Factor Receptor (EGFR) Amplification as a Target for Anti-EGFR Therapy: Analysis of Cell-Free Circulating Tumor DNA in Patients With Advanced Malignancies.

PurposeTo date, evidence for tissue epidermal growth factor receptor (EGFR) overexpression as a biomarker for anti-EGFR therapies has been weak. We investigated the genomic landscape of EGFR amplification in blood-derived cell-free tumor DNA (cfDNA) across diverse cancers and the role of anti-EGFR therapies in achieving response.MethodsWe assessed EGFR amplification status among 28,584 patients with malignancies evaluated by clinical-grade next-generation sequencing (NGS) of blood-derived cfDNA (54- to 73-gene panel). Furthermore, we curated the clinical characteristics of 1,434 patients at the University of California San Diego who had cfDNA testing by this NGS test.ResultsOverall, EGFR amplification was detected in cfDNA from 8.5% of patients (2,423 of 28,584), most commonly in colorectal (16.3% [458 of 2,807]), non-small-cell lung (9.0% [1,096 of 12,197]), and genitourinary cancers (8.1% [170 of 2,104]). Most patients had genomic coalterations (96.9% [95 of 98]), frequently involving genes affecting other tyrosine kinases (72.4% [71 of 98]), mitogen-activated protein kinase cascades (56.1% [55 of 98]), cell-cycle-associated signals (52.0% [51 of 98]), and the phosphoinositide 3-kinase pathway (35.7% [35 of 98]). EGFR amplification emerged in serial cfDNA after various anticancer therapies (n = 6), including checkpoint inhibitors (n = 4), suggesting a possible role for these amplifications in acquired resistance. Nine evaluable patients with EGFR amplification were treated with anti-EGFR-based regimens; five (55.6%) achieved partial responses, including three patients whose tissue NGS lacked EGFR amplification.ConclusionEGFR amplification was detected in cfDNA among 8.5% of 28,584 diverse cancers. Most patients had coexisting alterations. Responses were observed in five of nine patients who received EGFR inhibitors. Incorporating EGFR inhibitors into the treatment regimens of patients harboring EGFR amplification in cfDNA merits additional study

Building on the Past - Looking to the Future: A Focus on Payload Safety

The history of the space industry stretches far and above lunar landings to the construction of the International Space Station. For years, humans have sought to understand the nature of the universe. As society grows in knowledge and curiosity of space, the focus of maintaining the safety of the crew and vehicle habitability is of utmost importance to the National Aeronautics and Space Administration (NASA) community. Through the years, Payload Safety has developed not only as a Panel, but also as part of the NASA community, striving to enhance the efficiency and understanding of how business should be conducted as more International Partners become involved. This is the first in a series of papers and presentations in what is hoped to be an annual update that provides continuous challenges and lessons learned in the areas of communication, safety requirements and processes and other areas which have been vital to the Payload Safety Review Panel (PSRP)

Frzb modulates Wnt-9a-mediated β-catenin signaling during avian atrioventricular cardiac cushion development

AbstractNormal development of the cardiac atrioventricular (AV) endocardial cushions is essential for proper ventricular septation and morphogenesis of the mature mitral and tricuspid valves. In this study, we demonstrate spatially restricted expression of both Wnt-9a (formerly Wnt-14) and the secreted Wnt antagonist Frzb in AV endocardial cushions of the developing chicken heart. Wnt-9a expression is detected only in AV canal endocardial cells, while Frzb expression is detected in both endocardial and transformed mesenchymal cells of the developing AV cardiac cushions. We present evidence that Wnt-9a promotes cell proliferation in the AV canal and overexpression of Wnt-9a in ovo results in enlarged endocardial cushions and AV inlet obstruction. Wnt-9a stimulates β-catenin-responsive transcription in AV canal cells, duplicates the embryonic axis upon ventral injections in Xenopus embryos and appears to regulate cell proliferation by activating a Wnt/β-catenin signaling pathway. Additional functional studies reveal that Frzb inhibits Wnt-9a-mediated cell proliferation in cardiac cushions. Together, these data argue that Wnt-9a and Frzb regulate mesenchymal cell proliferation leading to proper AV canal cushion outgrowth and remodeling in the developing avian heart

Superoxide dismutase downregulation in osteoarthritis progression and end-stage disease

Oxidative stress is proposed as an important factor in osteoarthritis (OA). To investigate the expression of the three superoxide dismutase (SOD) antioxidant enzymes in OA. SOD expression was determined by real-time PCR and immunohistochemistry using human femoral head cartilage. SOD2 expression in Dunkin–Hartley guinea pig knee articular cartilage was determined by immunohistochemistry. The DNA methylation status of the SOD2 promoter was determined using bisulphite sequencing. RNA interference was used to determine the consequence of SOD2 depletion on the levels of reactive oxygen species (ROS) using MitoSOX and collagenases, matrix metalloproteinase 1 (MMP-1) and MMP-13, gene expression. All three SOD were abundantly expressed in human cartilage but were markedly downregulated in end-stage OA cartilage, especially SOD2. In the Dunkin–Hartley guinea pig spontaneous OA model, SOD2 expression was decreased in the medial tibial condyle cartilage before, and after, the development of OA-like lesions. The SOD2 promoter had significant DNA methylation alterations in OA cartilage. Depletion of SOD2 in chondrocytes increased ROS but decreased collagenase expression. This is the first comprehensive expression profile of all SOD genes in cartilage and, importantly, using an animal model, it has been shown that a reduction in SOD2 is associated with the earliest stages of OA. A decrease in SOD2 was found to be associated with an increase in ROS but a reduction of collagenase gene expression, demonstrating the complexities of ROS function

FOREIGN AGRICULTURAL POLICY AND FAR EAST FARM MARKETS

Agricultural and Food Policy,

Turbomachinery Clearance Control

Controlling interface clearances is the most cost effective method of enhancing turbomachinery performance. Seals control turbomachinery leakages, coolant flows and contribute to overall system rotordynamic stability. In many instances, sealing interfaces and coatings are sacrificial, like lubricants, giving up their integrity for the benefit of the component. They are subjected to abrasion, erosion, oxidation, incursive rubs, foreign object damage (FOD) and deposits as well as extremes in thermal, mechanical, aerodynamic and impact loadings. Tribological pairing of materials control how well and how long these interfaces will be effective in controlling flow. A variety of seal types and materials are required to satisfy turbomachinery sealing demands. These seals must be properly designed to maintain the interface clearances. In some cases, this will mean machining adjacent surfaces, yet in many other applications, coatings are employed for optimum performance. Many seals are coating composites fabricated on superstructures or substrates that are coated with sacrificial materials which can be refurbished either in situ or by removal, stripping, recoating and replacing until substrate life is exceeded. For blade and knife tip sealing an important class of materials known as abradables permit blade or knife rubbing without significant damage or wear to the rotating element while maintaining an effective sealing interface. Most such tip interfaces are passive, yet some, as for the high-pressure turbine (HPT) case or shroud, are actively controlled. This work presents an overview of turbomachinery sealing. Areas covered include: characteristics of gas and steam turbine sealing applications and environments, benefits of sealing, types of standard static and dynamics seals, advanced seal designs, as well as life and limitations issues

Strong environment X genotype interactions determine the fitness costs of antibiotic resistance in vitro and in an insect model of infection (article)

This is the author accepted manuscript. The final version is available from the American Society for Microbiology via the DOI in this record.The dataset associated with this article is located in ORE at: https://doi.org/10.24378/exe.2503The acquisition of antibiotic resistance commonly imposes fitness costs, a reduction in the fitness of bacteria in the absence of drugs. These costs have been primarily quantified using in vitro experiments and a small number of in vivo studies in mice, and it is commonly assumed that these diverse methods are consistent. Here, we used an insect model of infection to compare the fitness costs of antibiotic resistance in vivo relative to in vitro conditions. Experiments explored diverse mechanisms of resistance in a Gram-positive pathogen, Bacillus thuringiensis, and a Gram-negative intestinal symbiont, Enterobacter cloacae. Rifampicin resistance in B. thuringiensis showed fitness costs that were typically elevated in vivo, although these were modulated by genotype-environment interactions. In contrast, resistance to cefotaxime via de-repression of AmpC β-lactamase in E. cloacae resulted in undetectable costs in vivo or in vitro, while spontaneous resistance to nalidixic acid, and carriage of the IncP plasmid RP4, imposed costs that increased in vivo. Overall, fitness costs in vitro were a poor predictor of fitness costs in vivo because of strong genotype environment interactions throughout this study. Insect infections provide a cheap and accessible means of assessing fitness consequences of resistance mutations, data that is important to understand the evolution and spread of resistance. This study emphasizes that the fitness costs imposed by particular mutations or different modes of resistance are extremely variable, and that only a subset of these mutations are likely to be prevalent outside of the laboratory.Medical Research Council (MRC