Defects in BRCA1, BRCA2, and other members of the homologous recombination pathway have potential therapeutic relevance when used to support agents that introduce or exploit double-stranded DNA ...breaks. This study examines the association between homologous recombination defects and genomic patterns of loss of heterozygosity (LOH).
Ovarian tumours from two independent data sets were characterised for defects in BRCA1, BRCA2, and RAD51C, and LOH profiles were generated. Publically available data were downloaded for a third independent data set. The same analyses were performed on 57 cancer cell lines.
Loss of heterozygosity regions of intermediate size were observed more frequently in tumours with defective BRCA1 or BRCA2 (P=10(-11)). The homologous recombination deficiency (HRD) score was defined as the number of these regions observed in a tumour sample. The association between HRD score and BRCA deficiency was validated in two independent ovarian cancer data sets (P=10(-5) and 10(-29)), and identified breast and pancreatic cell lines with BRCA defects.
The HRD score appears capable of detecting homologous recombination defects regardless of aetiology or mechanism. This score could facilitate the use of PARP inhibitors and platinum in breast, ovarian, and other cancers.
High-mass stars are cosmic engines known to dominate the energetics in the Milky Way and other galaxies. However, their formation is still not well understood. Massive, cold, dense clouds, often ...appearing as infrared dark clouds (IRDCs), are the nurseries of massive stars. No measurements of magnetic fields in IRDCs in a state prior to the onset of high-mass star formation (HMSF) have previously been available, and prevailing HMSF theories do not consider strong magnetic fields. Here, we report observations of magnetic fields in two of the most massive IRDCs in the Milky Way. We show that IRDCs G11.11-0.12 and G0.253+0.016 are strongly magnetized and that the strong magnetic field is as important as turbulence and gravity for HMSF. The main dense filament in G11.11-0.12 is perpendicular to the magnetic field, while the lower density filament merging onto the main filament is parallel to the magnetic field. The implied magnetic field is strong enough to suppress fragmentation sufficiently to allow HMSF. Other mechanisms reducing fragmentation, such as the entrapment of heating from young stars via high-mass surface densities, are not required to facilitate HMSF.
Human epidermal growth factor receptor 2 (HER2)-low breast cancer has recently emerged as a targetable subset of breast tumors, based on the evidence from clinical trials of novel anti-HER2 ...antibody–drug conjugates. This evolution has raised several biological and clinical questions, warranting the establishment of consensus to optimally treat patients with HER2-low breast tumors. Between 2022 and 2023, the European Society for Medical Oncology (ESMO) held a virtual consensus-building process focused on HER2-low breast cancer. The consensus included a multidisciplinary panel of 32 leading experts in the management of breast cancer from nine different countries. The aim of the consensus was to develop statements on topics that are not covered in detail in the current ESMO Clinical Practice Guideline. The main topics identified for discussion were (i) biology of HER2-low breast cancer; (ii) pathologic diagnosis of HER2-low breast cancer; (iii) clinical management of HER2-low metastatic breast cancer; and (iv) clinical trial design for HER2-low breast cancer. The expert panel was divided into four working groups to address questions relating to one of the four topics outlined above. A review of the relevant scientific literature was conducted in advance. Consensus statements were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This article presents the developed statements, including findings from the expert panel discussions, expert opinion, and a summary of evidence supporting each statement.
•Targeting HER2-low expression with novel antibody-drug conjugates has reshaped the treatment of metastatic breast cancer.•This advancement raised relevant questions pertaining to the definition, diagnosis and management of HER2-low breast cancer.•We gathered 32 international experts to build consensus regarding key controversial topics pertaining HER2-low breast cancer.•A modified Delphi voting methodology was deployed, leading to 20 consensus statements, each with at least 90% consensus among experts.•Ongoing studies may lead to further refinement in our understanding of HER2-low breast cancer.
Context. With more than 1000 h of observation from Feb. 2016 to Oct. 2019, the Spitzer Exploration Program Red Worlds (ID: 13067, 13175 and 14223) exclusively targeted TRAPPIST-1, a nearby (12 pc) ...ultracool dwarf star, finding that it is orbited by seven transiting Earth-sized planets. At least three of these planets orbit within the classical habitable zone of the star, and all of them are well-suited for a detailed atmospheric characterization with the upcoming JWST. Aims. The main goals of the Spitzer Red Worlds program were (1) to explore the system for new transiting planets, (2) to intensively monitor the planets’ transits to yield the strongest possible constraints on their masses, sizes, compositions, and dynamics, and (3) to assess the infrared variability of the host star. In this paper, we present the global results of the project. Methods. We analyzed 88 new transits and combined them with 100 previously analyzed transits, for a total of 188 transits observed at 3.6 or 4.5 μ m. For a comprehensive study, we analyzed all light curves both individually and globally. We also analyzed 29 occultations (secondary eclipses) of planet b and eight occultations of planet c observed at 4.5 μ m to constrain the brightness temperatures of their daysides. Results. We identify several orphan transit-like structures in our Spitzer photometry, but all of them are of low significance. We do not confirm any new transiting planets. We do not detect any significant variation of the transit depths of the planets throughout the different campaigns. Comparing our individual and global analyses of the transits, we estimate for TRAPPIST-1 transit depth measurements mean noise floors of ~35 and 25 ppm in channels 1 and 2 of Spitzer /IRAC, respectively. We estimate that most of this noise floor is of instrumental origins and due to the large inter-pixel inhomogeneity of IRAC InSb arrays, and that the much better interpixel homogeneity of JWST instruments should result in noise floors as low as 10 ppm, which is low enough to enable the atmospheric characterization of the planets by transit transmission spectroscopy. Our analysis reveals a few outlier transits, but we cannot conclude whether or not they correspond to spot or faculae crossing events. We construct updated broadband transmission spectra for all seven planets which show consistent transit depths between the two Spitzer channels. Although we are limited by instrumental precision, the combined transmission spectrum of planet b to g tells us that their atmospheres seem unlikely to be CH 4 -dominated. We identify and model five distinct high energy flares in the whole dataset, and discuss our results in the context of habitability. Finally, we fail to detect occultation signals of planets b and c at 4.5 μ m, and can only set 3- σ upper limits on their dayside brightness temperatures (611 K for b 586 K for c).
The electronic properties of thiol‐functionalized 2D MoS2 nanosheets are investigated. Shifts in the valence and conduction bands and Fermi levels are observed while bandgaps remain unaffected. These ...findings allow the tuning of energy barriers between 2D MoS2 and other materials, which can lead to improved control over 2D MoS2‐based electronic and optical devices and catalysts.
Early 2017 observations of TRAPPIST-1 with Spitzer Delrez, L; Gillon, M; Triaud, A H M J ...
Monthly notices of the Royal Astronomical Society,
04/2018, Letnik:
475, Številka:
3
Journal Article, Web Resource
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Abstract
The recently detected TRAPPIST-1 planetary system, with its seven planets transiting a nearby ultracool dwarf star, offers the first opportunity to perform comparative exoplanetology of ...temperate Earth-sized worlds. To further advance our understanding of these planets’ compositions, energy budgets, and dynamics, we are carrying out an intensive photometric monitoring campaign of their transits with the Spitzer Space Telescope. In this context, we present 60 new transits of the TRAPPIST-1 planets observed with Spitzer/Infrared Array Camera (IRAC) in 2017 February and March. We combine these observations with previously published Spitzer transit photometry and perform a global analysis of the resulting extensive data set. This analysis refines the transit parameters and provides revised values for the planets’ physical parameters, notably their radii, using updated properties for the star. As part of our study, we also measure precise transit timings that will be used in a companion paper to refine the planets’ masses and compositions using the transit timing variations method. TRAPPIST-1 shows a very low level of low-frequency variability in the IRAC 4.5-μm band, with a photometric RMS of only 0.11 per cent at a 123-s cadence. We do not detect any evidence of a (quasi-)periodic signal related to stellar rotation. We also analyse the transit light curves individually, to search for possible variations in the transit parameters of each planet due to stellar variability, and find that the Spitzer transits of the planets are mostly immune to the effects of stellar variations. These results are encouraging for forthcoming transmission spectroscopy observations of the TRAPPIST-1 planets with the James Webb Space Telescope.
ER-positive (ER+ ) breast cancer includes all of the intrinsic molecular subtypes, although the luminal A and B subtypes predominate. In this study, we evaluated the ability of six clinically ...relevant genomic signatures to predict relapse in patients with ER+ tumors treated with adjuvant tamoxifen only.
Four microarray datasets were combined and research-based versions of PAM50 intrinsic subtyping and risk of relapse (PAM50-ROR) score, 21-gene recurrence score (OncotypeDX), Mammaprint, Rotterdam 76 gene, index of sensitivity to endocrine therapy (SET) and an estrogen-induced gene set were evaluated. Distant relapse-free survival (DRFS) was estimated by Kaplan–Meier and log-rank tests, and multivariable analyses were done using Cox regression analysis. Harrell's C-index was also used to estimate performance.
All signatures were prognostic in patients with ER+ node-negative tumors, whereas most were prognostic in ER+ node-positive disease. Among the signatures evaluated, PAM50-ROR, OncotypeDX, Mammaprint and SET were consistently found to be independent predictors of relapse. A combination of all signatures significantly increased the performance prediction. Importantly, low-risk tumors (>90% DRFS at 8.5 years) were identified by the majority of signatures only within node-negative disease, and these tumors were mostly luminal A (78%–100%).
Most established genomic signatures were successful in outcome predictions in ER+ breast cancer and provided statistically independent information. From a clinical perspective, multiple signatures combined together most accurately predicted outcome, but a common finding was that each signature identified a subset of luminal A patients with node-negative disease who might be considered suitable candidates for adjuvant endocrine therapy alone.
We combine Spitzer and ground-based Korea Microlensing Telescope Network microlensing observations to identify and precisely measure an Earth-mass ( ) planet OGLE-2016-BLG-1195Lb at orbiting a ...ultracool dwarf. This is the lowest-mass microlensing planet to date. At kpc, it is the third consecutive case among the Spitzer "Galactic distribution" planets toward the Galactic bulge that lies in the Galactic disk as opposed to the bulge itself, hinting at a skewed distribution of planets. Together with previous microlensing discoveries, the seven Earth-size planets orbiting the ultracool dwarf TRAPPIST-1, and the detection of disks around young brown dwarfs, OGLE-2016-BLG-1195Lb suggests that such planets might be common around ultracool dwarfs. It therefore sheds light on the formation of both ultracool dwarfs and planetary systems at the limit of low-mass protoplanetary disks.
Moist calcium silicate minerals are known to readily react with carbon dioxide (CO2). The reaction products can cause rapid hardening and result in the production of monolithic materials. Today, ...accelerated carbonation is a developing technology, which may have potential for the treatment of wastes and contaminated soils and for the sequestration of CO2, an important greenhouse gas. This paper reviews recent developments in this emerging technology and provides information on the parameters that control the process. The effects of the accelerated carbonation reaction on the solid phase are discussed and future potential applications of this technology are also considered.
Ammonia in infrared dark clouds Pillai, T.; Wyrowski, F.; Carey, S. J. ...
Astronomy and astrophysics (Berlin),
05/2006, Letnik:
450, Številka:
2
Journal Article
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Context.While low mass clouds have been relatively well studied, our picture of high-mass star formation remains unclear. Infrared Dark Clouds appear to be the long sought population of cold and ...dense aggregations with the potential of harbouring the earliest stages of massive star formation. Up to now there has been no systematic study on the temperature distribution, velocity fields, chemical and physical state toward this new cloud population. Aims.Knowing these properties is crucial for understanding the presence, absence and the very potential of star formation. The present paper aims at addressing these questions. We analyse temperature structures and velocity fields and gain information on their chemical evolution. Methods.We mapped the $(J,K) = (1,~1)$ and (2, 2) inversion transitions of ammonia in 9 infrared dark clouds. Our observations allow the most reliable determination of gas temperatures in IRDCs to date. Results.The gas emission is remarkably coextensive with the extinction seen at infrared wavelengths and with the submillimeter dust emission. Our results show that IRDCs are on average cold ($T < 20 ~ {\rm K}$) and have variations among the different cores. IRDC cores are in virial equilibrium, are massive ($M > 100 ~$${M}_\odot$), highly turbulent (1–3 $ \rm km~s^{-1}$) and exhibit significant velocity structure (variations around 1–2 $\rm km~s^{-1}$ over the cloud). Conclusions.We find an increasing trend in temperature from IRDCs with high ammonia column density to high mass protostellar objects and Ultracompact Hii regions, stages of early warm high-mass star formation. The linewidths of IRDCs are smaller than those observed in high mass protostellar objects and hot core/Ultracompact Hii regions. On basis of this sample, and by comparison of the ammonia gas properties within a cloud and between different clouds, we infer that while active star formation is not yet pervasive in most IRDCs, local condensations might collapse in the future or have already begun forming stars.
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