The 2021 outburst of the recurrent nova RS Ophiuchi observed in X-rays by the Neil Gehrels Swift Observatory: a comparative study

On 2021 August 8, the recurrent nova RS Ophiuchi erupted again, after an interval of 15.5 yr. Regular monitoring by the Neil Gehrels Swift Observatory began promptly, on August 9.9 (0.37 day after the optical peak), and continued until the source passed behind the Sun at the start of November, 86 days later. Observations then restarted on day 197, once RS Oph emerged from the Sun constraint. This makes RS Oph the first Galactic recurrent nova to have been monitored by Swift throughout two eruptions. Here we investigate the extensive X-ray datasets from 2006 and 2021, as well as the more limited data collected by EXOSAT in 1985. The hard X-rays arising from shock interactions between the nova ejecta and red giant wind are similar following the last two eruptions. In contrast, the early super-soft source (SSS) in 2021 was both less variable and significantly fainter than in 2006. However, 0.3–1 keV light-curves from 2021 reveal a 35 s quasi-periodic oscillation consistent in frequency with the 2006 data. The Swift X-ray spectra from 2021 are featureless, with the soft emission typically being well parametrized by a simple blackbody, while the 2006 spectra showed much stronger evidence for superimposed ionized absorption edges. Considering the data after day 60 following each eruption, during the supersoft phase the 2021 spectra are hotter, with smaller effective radii and lower wind absorption, leading to an apparently reduced bolometric luminosity. We explore possible explanations for the gross differences in observed SSS behaviour between the 2006 and 2021 outbursts

Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer

Background Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER+) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth factor pathways, circumventing the need for steroid hormones. Previously, we reported the anti-proliferative effect of everolimus (RAD001-mTORC1 inhibitor) with endocrine therapy in resistance models; however, potential routes of escape from treatment via ERBB2/3 signalling were observed. We hypothesised that combined targeting of three cellular nodes (ER, ERBB, and mTORC1) may provide enhanced long-term clinical utility. Methods A panel of ER+ BC cell lines adapted to long-term oestrogen deprivation (LTED) and expressing ESR1wt or ESR1Y537S, modelling acquired resistance to an aromatase-inhibitor (AI), were treated in vitro with a combination of RAD001 and neratinib (pan-ERBB inhibitor) in the presence or absence of oestradiol (E2), tamoxifen (4-OHT), or fulvestrant (ICI182780). End points included proliferation, cell signalling, cell cycle, and effect on ER-mediated transactivation. An in-vivo model of AI resistance was treated with monotherapies and combinations to assess the efficacy in delaying tumour progression. RNA-seq analysis was performed to identify changes in global gene expression as a result of the indicated therapies. Results Here, we show RAD001 and neratinib (pan-ERBB inhibitor) caused a concentration-dependent decrease in proliferation, irrespective of the ESR1 mutation status. The combination of either agent with endocrine therapy further reduced proliferation but the maximum effect was observed with a triple combination of RAD001, neratinib, and endocrine therapy. In the absence of oestrogen, RAD001 caused a reduction in ER-mediated transcription in the majority of the cell lines, which associated with a decrease in recruitment of ER to an oestrogen-response element on the TFF1 promoter. Contrastingly, neratinib increased both ER-mediated transactivation and ER recruitment, an effect reduced by the addition of RAD001. In-vivo analysis of an LTED model showed the triple combination of RAD001, neratinib, and fulvestrant was most effective at reducing tumour volume. Gene set enrichment analysis revealed that the addition of neratinib negated the epidermal growth factor (EGF)/EGF receptor feedback loops associated with RAD001. Conclusions Our data support the combination of therapies targeting ERBB2/3 and mTORC1 signalling, together with fulvestrant, in patients who relapse on endocrine therapy and retain a functional ER

Swift detection of the super-swift switch-on of the super-soft phase in nova V745 Sco (2014)

V745 Sco is a recurrent nova, with the most recent eruption occurring in February 2014. V745 Sco was first observed by Swift a mere 3.7 hr after the announcement of the optical discovery, with the super-soft X-ray emission being detected around four days later and lasting for only ~two days, making it both the fastest follow-up of a nova by Swift and the earliest switch-on of super-soft emission yet detected. Such an early switch-on time suggests a combination of a very high velocity outflow and low ejected mass and, together with the high effective temperature reached by the super-soft emission, a high mass white dwarf (>1.3 M_sun). The X-ray spectral evolution was followed from an early epoch where shocked emission was evident, through the entirety of the super-soft phase, showing evolving column density, emission lines, absorption edges and thermal continuum temperature. UV grism data were also obtained throughout the super-soft interval, with the spectra showing mainly emission lines from lower ionization transitions and the Balmer continuum in emission. V745 Sco is compared with both V2491 Cyg (another nova with a very short super-soft phase) and M31N 2008-12a (the most rapidly recurring nova yet discovered). The longer recurrence time compared to M31N 2008-12a could be due to a lower mass accretion rate, although inclination of the system may also play a part. Nova V745 Sco (2014) revealed the fastest evolving super-soft source phase yet discovered, providing a detailed and informative dataset for study

Impact of progressive global warming on the global-scale yield of maize and soybean

Global surface temperature is projected to warm over the coming decades, with regional differences expected in temperature change, rainfall and the frequency of extreme events. Temperature is a major determinant of crop growth and development, affecting planting date, growing season length and yield. We investigated the effects of increments of mean global temperature warming from 0.5 °C to 4 °C on soybean and maize development and yield, both globally and for the main producing countries, and simulated adaptation through changing planting date and variety. Increasing temperature resulted in reduced growing season lengths and ultimately reduced yields for both crops. The global yield for maize decreased as temperature increased, although the severity of the decrease was dependent on geographic region. Small temperature increases of 0.5 °C had no effect on soybean yield, although yield decreased as temperature increased. These negative effects, however, were partly compensated for by the implementation of adaptation strategies including planting earlier in the season and changing variety. The degree of compensation was dependent on geographical area and crop, with maize adaptation delaying the negative effects of temperature on yield, compared to soybean adaptation which increased yield in China, India and Korea DPR as well as delaying the effects in the remaining countries. The results of this paper indicate the degree to which farmer-controlled adaptation strategies can alleviate the negative impacts of increasing temperature on two major crop species

The role of multiple marks in epigenetic silencing and the emergence of a stable bivalent chromatin state

We introduce and analyze a minimal model of epigenetic silencing in budding yeast, built upon known biomolecular interactions in the system. Doing so, we identify the epigenetic marks essential for the bistability of epigenetic states. The model explicitly incorporates two key chromatin marks, namely H4K16 acetylation and H3K79 methylation, and explores whether the presence of multiple marks lead to a qualitatively different systems behavior. We find that having both modifications is important for the robustness of epigenetic silencing. Besides the silenced and transcriptionally active fate of chromatin, our model leads to a novel state with bivalent (i.e., both active and silencing) marks under certain perturbations (knock-out mutations, inhibition or enhancement of enzymatic activity). The bivalent state appears under several perturbations and is shown to result in patchy silencing. We also show that the titration effect, owing to a limited supply of silencing proteins, can result in counter-intuitive responses. The design principles of the silencing system is systematically investigated and disparate experimental observations are assessed within a single theoretical framework. Specifically, we discuss the behavior of Sir protein recruitment, spreading and stability of silenced regions in commonly-studied mutants (e.g., sas2, dot1) illuminating the controversial role of Dot1 in the systems biology of yeast silencing.Comment: Supplementary Material, 14 page

Agent based modelling helps in understanding the rules by which fibroblasts support keratinocyte colony formation

Background: Autologous keratincoytes are routinely expanded using irradiated mouse fibroblasts and bovine serum for clinical use. With growing concerns about the safety of these xenobiotic materials, it is desirable to culture keratinocytes in media without animal derived products. An improved understanding of epithelial/mesenchymal interactions could assist in this. Methodology/Principal Findings: A keratincyte/fibroblast o-culture model was developed by extending an agent-based keratinocyte colony formation model to include the response of keratinocytes to both fibroblasts and serum. The model was validated by comparison of the in virtuo and in vitro multicellular behaviour of keratinocytes and fibroblasts in single and co-culture in Greens medium. To test the robustness of the model, several properties of the fibroblasts were changed to investigate their influence on the multicellular morphogenesis of keratinocyes and fibroblasts. The model was then used to generate hypotheses to explore the interactions of both proliferative and growth arrested fibroblasts with keratinocytes. The key predictions arising from the model which were confirmed by in vitro experiments were that 1) the ratio of fibroblasts to keratinocytes would critically influence keratinocyte colony expansion, 2) this ratio needed to be optimum at the beginning of the co-culture, 3) proliferative fibroblasts would be more effective than irradiated cells in expanding keratinocytes and 4) in the presence of an adequate number of fibroblasts, keratinocyte expansion would be independent of serum. Conclusions: A closely associated computational and biological approach is a powerful tool for understanding complex biological systems such as the interactions between keratinocytes and fibroblasts. The key outcome of this study is the finding that the early addition of a critical ratio of proliferative fibroblasts can give rapid keratinocyte expansion without the use of irradiated mouse fibroblasts and bovine serum

The impacts of climate change across the globe: a multi-sectoral assessment

The overall global-scale consequences of climate change are dependent on the distribution of impacts across regions, and there are multiple dimensions to these impacts.This paper presents a global assessment of the potential impacts of climate change across several sectors, using a harmonised set of impacts models forced by the same climate and socio-economic scenarios. Indicators of impact cover the water resources, river and coastal flooding, agriculture, natural environment and built environment sectors. Impacts are assessed under four SRES socio-economic and emissions scenarios, and the effects of uncertainty in the projected pattern of climate change are incorporated by constructing climate scenarios from 21 global climate models. There is considerable uncertainty in projected regional impacts across the climate model scenarios, and coherent assessments of impacts across sectors and regions therefore must be based on each model pattern separately; using ensemble means, for example, reduces variability between sectors and indicators. An example narrative assessment is presented in the paper. Under this narrative approximately 1 billion people would be exposed to increased water resources stress, around 450 million people exposed to increased river flooding, and 1.3 million extra people would be flooded in coastal floods each year. Crop productivity would fall in most regions, and residential energy demands would be reduced in most regions because reduced heating demands would offset higher cooling demands. Most of the global impacts on water stress and flooding would be in Asia, but the proportional impacts in the Middle East North Africa region would be larger. By 2050 there are emerging differences in impact between different emissions and socio-economic scenarios even though the changes in temperature and sea level are similar, and these differences are greater in 2080. However, for all the indicators, the range in projected impacts between different climate models is considerably greater than the range between emissions and socio-economic scenarios

The AVOID programme’s new simulations of the global benefits of stringent climate change mitigation

Quantitative simulations of the global-scale benefits of climate change mitigation are presented, using a harmonised, self-consistent approach based on a single set of climate change scenarios. The approach draws on a synthesis of output from both physically-based and economics-based models, and incorporates uncertainty analyses. Previous studies have projected global and regional climate change and its impacts over the 21st century but have generally focused on analysis of business-as-usual scenarios, with no explicit mitigation policy included. This study finds that both the economics-based and physically-based models indicate that early, stringent mitigation would avoid a large proportion of the impacts of climate change projected for the 2080s. However, it also shows that not all the impacts can now be avoided, so that adaptation would also therefore be needed to avoid some of the potential damage. Delay in mitigation substantially reduces the percentage of impacts that can be avoided, providing strong new quantitative evidence for the need for stringent and prompt global mitigation action on greenhouse gas emissions, combined with effective adaptation, if large, widespread climate change impacts are to be avoided. Energy technology models suggest that such stringent and prompt mitigation action is technologically feasible, although the estimated costs vary depending on the specific modelling approach and assumptions

Quantitative Historical Change in Bumblebee (Bombus spp.) Assemblages of Red Clover Fields

Flower visiting insects provide a vitally important pollination service for many crops and wild plants. Recent decline of pollinating insects due to anthropogenic modification of habitats and climate, in particular from 1950's onwards, is a major and widespread concern. However, few studies document the extent of declines in species diversity, and no studies have previously quantified local abundance declines. We here make a quantitative assessment of recent historical changes in bumblebee assemblages by comparing contemporary and historical survey data. species observed in the 1930's, five species were not observed at present. The latter were all long-tongued, late-emerging species.Because bumblebees are important pollinators, historical changes in local bumblebee assemblages are expected to severely affect plant reproduction, in particular long-tubed species, which are pollinated by long-tongued bumblebees

The pathology of familial breast cancer: Immunohistochemistry and molecular analysis

Extensive studies of BRCA1- and BRCA2-associated breast tumours have been carried out in the few years since the identification of these familial breast cancer predisposing genes. The morphological studies suggest that BRCA1 tumours differ from BRCA2 tumours and from sporadic breast cancers. Recent progress in immunohistochemistry and molecular biology techniques has enabled in-depth investigation of molecular pathology of these tumours. Studies to date have investigated issues such as steroid hormone receptor expression, mutation status of tumour suppressor genes TP53 and c-erbB2, and expression profiles of cell cycle proteins p21, p27 and cyclin D(1). Despite relative paucity of data, strong evidence of unique biological characteristics of BRCA1-associated breast cancer is accumulating. BRCA1-associated tumours appear to show an increased frequency of TP53 mutations, frequent p53 protein stabilization and absence of imunoreactivity for steroid hormone receptors. Further studies of larger number of samples of both BRCA1- and BRCA2-associated tumours are necessary to clarify and confirm these observations