The Neon Abundance in the Ejecta of QU Vul From Late-Epoch IR Spectra

We present ground-based SpectroCam-10 mid-infrared, MMT optical, and Spitzer Space Telescope IRS mid-infrared spectra taken 7.62, 18.75, and 19.38 years respectively after the outburst of the old classical nova QU Vulpeculae (Nova Vul 1984 #2). The spectra of the ejecta are dominated by forbidden line emission from neon and oxygen. Our analysis shows that neon was, at the first and last epochs respectively, more than 76 and 168 times overabundant by number with respect to hydrogen compared to the solar value. These high lower limits to the neon abundance confirm that QU Vul involved a thermonuclear runaway on an ONeMg white dwarf and approach the yields predicted by models of the nucleosynthesis in such events.Comment: ApJ 2007 accepted, 18 pages, including 5 figures, 1 tabl

Parity and breast cancer risk among BRCA1 and BRCA2 mutation carriers.

INTRODUCTION: Increasing parity and age at first full-term pregnancy are established risk factors for breast cancer in the general population. However, their effects among BRCA1 and BRCA2 mutation carriers is still under debate. We used retrospective data on BRCA1 and BRCA2 mutation carriers from the UK to assess the effects of parity-related variables on breast cancer risk. METHODS: The data set included 457 mutation carriers who developed breast cancer (cases) and 332 healthy mutation carriers (controls), ascertained through families seen in genetic clinics. Hazard ratios were estimated by using a weighted cohort approach. RESULTS: Parous BRCA1 and BRCA2 mutation carriers were at a significantly lower risk of developing breast cancer (hazard ratio 0.54, 95% confidence interval 0.37 to 0.81; p = 0.002). The protective effect was observed only among carriers who were older than 40 years. Increasing age at first live birth was associated with an increased breast cancer risk among BRCA2 mutation carriers (p trend = 0.002) but not BRCA1 carriers. However, the analysis by age at first live birth was based on small numbers. CONCLUSION: The results suggest that the relative risks of breast cancer associated with parity among BRCA1 and BRCA2 mutation carriers may be similar to those in the general population and that reproductive history may be used to improve risk prediction in carriers.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Elemental Abundances in the Ejecta of Old Classical Novae from Late-Epoch Spitzer Spectra

We present Spitzer Space Telescope mid-infrared IRS spectra, supplemented by ground-based optical observations, of the classical novae V1974 Cyg, V382 Vel, and V1494 Aql more than 11, 8, and 4 years after outburst respectively. The spectra are dominated by forbidden emission from neon and oxygen, though in some cases, there are weak signatures of magnesium, sulfur, and argon. We investigate the geometry and distribution of the late time ejecta by examination of the emission line profiles. Using nebular analysis in the low density regime, we estimate lower limits on the abundances in these novae. In V1974 Cyg and V382 Vel, our observations confirm the abundance estimates presented by other authors and support the claims that these eruptions occurred on ONe white dwarfs. We report the first detection of neon emission in V1494 Aql and show that the system most likely contains a CO white dwarf.Comment: 22 pages, 12 figure

Stellar Populations and Mass-Loss in M15: A Spitzer Detection of Dust in the Intra-Cluster Medium

We present Spitzer Space Telescope IRAC and MIPS observations of the galactic globular cluster M15 (NGC 7078), one of the most metal-poor clusters with a [Fe/H] = -2.4. Our Spitzer images reveal a population of dusty red giants near the cluster center, a previously detected planetary nebula (PN) designated K648, and a possible detection of the intra-cluster medium (ICM) arising from mass loss episodes from the evolved stellar population. Our analysis suggests 9 (+/-2) x 10^-4 solar masses of dust is present in the core of M15, and this material has accumulated over a period of approximately 10^6 years, a timescale ten times shorter than the last galactic plane crossing event. We also present Spitzer IRS follow up observations of K648, including the detection of the [NeII] 12.81 micron line, and discuss abundances derived from infrared fine structure lines.Comment: Accepted for publication in AJ. 20 pages, 10 figures, 6 tables. Full resolution versions of figures 1, 5, 7, and 8 are available in a PDF version of this manuscript at http://ir.astro.umn.edu/~mboyer/ms_060906.pd

Real-World Concordance between Germline and Tumour <i>BRCA1/2</i> Status in Epithelial Ovarian Cancer

Patients diagnosed with epithelial ovarian cancer may undergo reflex tumour BRCA1/ 2 testing followed by germline BRCA1/2 testing in patients with a positive tumour test result. This testing model relies on tumour BRCA1/ 2 tests being able to detect all types of pathogenic variant. We analysed germline and tumour BRCA1/2 test results from patients treated for epithelial ovarian cancer at our specialist oncological referral centre. Tumour BRCA1/2 testing was performed using the next-generation sequencing (NGS)-based myChoice ® companion diagnostic (CDx; Myriad Genetics, Inc.). Germline BRCA1/2 testing was performed in the North West Genomic Laboratory Hub using NGS and multiplex ligation-dependent probe amplification. Between 11 April 2021 and 11 October 2023, 382 patients were successfully tested for tumour BRCA1 and BRCA2 variants. Of these, 367 (96.1%) patients were tested for germline BRCA1/ 2 variants. In those patients who underwent tumour and germline testing, 15.3% (56/367) had a BRCA1/ 2 pathogenic variant (36 germline and 20 somatic). All germline BRCA1/2 pathogenic small sequencing variants were detected in tumour DNA. By contrast, 3 out of 8 germline BRCA1/2 pathogenic large rearrangements were not reported in tumour DNA. The overall concordance of germline BRCA1/2 pathogenic variants detected in germline and tumour DNA was clinically acceptable at 91.7% (33/36). The myChoice ® CDx was able to detect most germline BRCA1/2 pathogenic variants in tumour DNA, although a proportion of pathogenic large rearrangements were not reported. If Myriad's myChoice ® CDx is used for tumour BRCA1/2 testing, our data supports a testing strategy of germline and tumour BRCA1/2 testing in all patients diagnosed with epithelial ovarian cancer aged &lt; 79 years old, with germline BRCA1/2 testing only necessary for patients aged ≥ 80 years old with a tumour BRCA1/2 pathogenic variant. </p

P-rex1 cooperates with PDGFRβ to drive cellular migration in 3D microenvironments

Expression of the Rac-guanine nucleotide exchange factor (RacGEF), P-Rex1 is a key determinant of progression to metastasis in a number of human cancers. In accordance with this proposed role in cancer cell invasion and metastasis, we find that ectopic expression of P-Rex1 in an immortalised human fibroblast cell line is sufficient to drive multiple migratory and invasive phenotypes. The invasive phenotype is greatly enhanced by the presence of a gradient of serum or platelet-derived growth factor, and is dependent upon the expression of functional PDGF receptor β. Consistently, the invasiveness of WM852 melanoma cells, which endogenously express P-Rex1 and PDGFRβ, is opposed by siRNA of either of these proteins. Furthermore, the current model of P-Rex1 activation is advanced through demonstration of P-Rex1 and PDGFRβ as components of the same macromolecular complex. These data suggest that P-Rex1 has an influence on physiological migratory processes, such as invasion of cancer cells, both through effects upon classical Rac1-driven motility and a novel association with RTK signalling complexes

Design, and synthesis of selectively anticancer 4-cyanophenyl substituted thiazol-2-ylhydrazones

Cyclization of substituted thiosemicarbazones with α-bromo-4-cyanoacetophenone allows rapid single-step sustainable syntheses of 4-cyanophenyl-2-hydrazinylthiazoles libraries (30 examples, 66–79%). All show anticancer efficacy against HCT-116 and MCF-7 carcinoma cell lines with the majority being more active than cisplatin positive controls. The compounds 2-(2-(2-hydroxy-3-methylbenzylidene) hydrazinyl)-4-(4-cyanophenyl)thiazole (3f) and 2-(2-((pentafluorophenyl)methylene)-hydrazinyl)-4-(4-cyanophenyl) thiazole (3a′) show optimal GI50 values (1.0 ± 0.1 μM and 1.7 ± 0.3 μM) against MCF-7 breast cancer cells. Against colorectal carcinoma HCT-116 cells, (2-(2-(3-bromothiophen-2yl)methylene)hydrazinyl)-4-(4-cyanophenyl)thiazole (3b′), 2-(2-(2-hydroxy-3-methylbenzylidene) hydrazinyl)-4-(4-cyanophenyl)thiazole (3f), 2-(2-(2,6-dichlorobenzylidene)hydrazinyl)-4-(4-cyanophenyl)thiazole (3f) and 2-(2-(1-(4-fluorophenyl)ethylidene)hydrazinyl)-4-(4-cyanophenyl) thiazole (3w) are the most active (GI50 values: 1.6 ± 0.2, 1.6 ± 0.1, 1.1 ± 0.5 and 1.5 ± 0.8 μM respectively). Control studies with MRC-5 cells indicate appreciable selectivity towards the cancer cells targeted. Significant (p < 0.005) growth inhibition and cytotoxicity effects for the thiazoles 3 were corroborated by cell count and clonogenic assays using the same cancer cell lines at 5 and 10 μM agent concentrations. Cell cycle, caspase activation and Western blot assays demonstrated that compounds 3b′ and 3f induce cancer cell death via caspase-dependent apoptosis. The combination of straight forward synthesis and high activity makes the thiazoles 3 an interesting lead for further development

Active Ooid Growth Driven By Sediment Transport in a High-Energy Shoal, Little Ambergris Cay, Turks and Caicos Islands

Ooids are a common component of carbonate successions of all ages and present significant potential as paleoenvironmental proxies, if the mechanisms that control their formation and growth can be understood quantitatively. There are a number of hypotheses about the controls on ooid growth, each offering different ideas on where and how ooids accrete and what role, if any, sediment transport and abrasion might play. These hypotheses have not been well tested in the field, largely due to the inherent challenges of tracking individual grains over long timescales. This study presents a detailed field test of ooid-growth hypotheses on Little Ambergris Cay in the Turks and Caicos Islands, British Overseas Territories. This field site is characterized by westward net sediment transport from waves driven by persistent easterly trade winds. This configuration makes it possible to track changes in ooid properties along their transport path as a proxy for changes in time. Ooid size, shape, and radiocarbon age were compared along this path to determine in which environments ooids are growing or abrading. Ooid surface textures, petrographic fabrics, stable-isotope compositions (δ^(13)C, δ^(18)O, and δ^(34)S), lipid geochemistry, and genetic data were compared to characterize mechanisms of precipitation and degradation and to determine the relative contributions of abiotic (e.g., abiotic precipitation, physical abrasion) and biologically influenced processes (e.g., biologically mediated precipitation, fabric destruction through microbial microboring and micritization) to grain size and character. A convergence of evidence shows that active ooid growth occurs along the transport path in a high-energy shoal environment characterized by frequent suspended-load transport: median ooid size increases by more than 100 μm and bulk radiocarbon ages decrease by 360 yr westward along the ∼ 20 km length of the shoal crest. Lipid and 16S rRNA data highlight a spatial disconnect between the environments with the most extensive biofilm colonization and environments with active ooid growth. Stable-isotope compositions are indistinguishable among samples, and are consistent with abiotic precipitation of aragonite from seawater. Westward increases in ooid sphericity and the abundance of well-polished ooids illustrate that ooids experience subequal amounts of growth and abrasion—in favor of net growth—as they are transported along the shoal crest. Overall, these results demonstrate that, in the Ambergris system, the mechanism of ooid growth is dominantly abiotic and the loci of ooid growth is determined by both carbonate saturation and sediment transport mode. Microbes play a largely destructive, rather than constructive, role in ooid size and fabric

Catalysis enabled synthesis, structures, and reactivities of fluorinated S8-corona[n]arenes (n = 8–12)

Previously inaccessible large S8-corona[n]arene macrocycles (n = 8–12) with alternating aryl and 1,4-C6F4 subunits are easily prepared on up to gram scales, without the need for chromatography (up to 45% yield, 10 different examples) through new high acceleration SNAr substitution protocols (catalytic NR4F in pyridine, R = H, Me, Bu). Macrocycle size and functionality are tunable by precursor and catalyst selection. Equivalent simple NR4F catalysis allows facile late-stage SNAr difunctionalisation of the ring C6F4 units with thiols (8 derivatives, typically 95+% yields) providing two-step access to highly functionalised fluoromacrocycle libraries. Macrocycle host binding supports fluoroaryl catalytic activation through contact ion pair binding of NR4F and solvent inclusion. In the solid-state, solvent inclusion also intimately controls macrocycle conformation and fluorine–fluorine interactions leading to spontaneous self-assembly into infinite columns with honeycomb-like lattices