585 research outputs found

    Microwave Limb Sounder (MLS) observations of biomass burning products in the stratosphere from Canadian forest fires in August 2017

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    Forest fires in British Columbia in August 2017 caused a pyrocumulonimbus event that injected a polluted air mass into the lower stratosphere. The Microwave Limb Sounder (MLS) on the Aura satellite first observed the polluted air mass on 14 August 2017 and continued to observe it for 60 d (100 d in water vapour). We estimate the mass of CO injected into the stratosphere to be 2400 Gg. Events in which a fire injects its burning products directly into the stratosphere are rare: this is the third of four such events in the 16 years since the launch of Aura, the second largest of the four events, and the only one in the Northern Hemisphere. The other three events occurred in Australia in December 2006, February 2009 and from December 2019 to January 2020. Unlike the 2006 and 2009 events, but like the 2019–2020 event, the polluted air mass described here had a clearly elevated water vapour content: between 2.5 and 5 times greater than that in the surrounding atmosphere. We describe the evolution of the polluted air mass, showing that it rose to an altitude of about 24 km (31 hPa) and divided into several identifiable parts. In addition to CO and H2O, we observe enhanced amounts of HCN, CH3CN, CH3Cl and CH3OH with mixing ratios in the range to be expected from a variety of measurements in other biomass burning plumes. We use back trajectories and plume-dispersion modelling to demonstrate that the pollutants observed by MLS originated in the British Columbia fires, the likeliest source being at 53.2∘ N, 121.8∘ W at 05:20 UTC on 13 August 2017.</p

    Reconciling intrinsic properties of activating TNF receptors by native ligands versus synthetic agonists

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    The extracellular domain of tumor necrosis factor receptors (TNFR) generally require assembly into a homotrimeric quaternary structure as a prerequisite for initiation of signaling via the cytoplasmic domains. TNF receptor homotrimers are natively activated by similarly homo-trimerized TNF ligands, but can also be activated by synthetic agonists including engineered antibodies and Fc-ligand fusion proteins. A large body of literature from pre-clinical models supports the hypothesis that synthetic agonists targeting a diverse range of TNF receptors (including 4-1BB, CD40, OX40, GITR, DR5, TNFRSF25, HVEM, LTβR, CD27, and CD30) could amplify immune responses to provide clinical benefit in patients with infectious diseases or cancer. Unfortunately, however, the pre-clinical attributes of synthetic TNF receptor agonists have not translated well in human clinical studies, and have instead raised fundamental questions regarding the intrinsic biology of TNF receptors. Clinical observations of bell-shaped dose response curves have led some to hypothesize that TNF receptor overstimulation is possible and can lead to anergy and/or activation induced cell death of target cells. Safety issues including liver toxicity and cytokine release syndrome have also been observed in humans, raising questions as to whether those toxicities are driven by overstimulation of the targeted TNF receptor, a non-TNF receptor related attribute of the synthetic agonist, or both. Together, these clinical findings have limited the development of many TNF receptor agonists, and may have prevented generation of clinical data which reflects the full potential of TNF receptor agonism. A number of recent studies have provided structural insights into how different TNF receptor agonists bind and cluster TNF receptors, and these insights aid in deconvoluting the intrinsic biology of TNF receptors with the mechanistic underpinnings of synthetic TNF receptor agonist therapeutics

    Romantic ideals, mate preferences, and anticipation of future difficulties in marital life: a comparative study of young adults in India and America

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    This article has been made available through open access by the Brunel Open Access Publishing Fund.Previous studies have established that Indians tend to be greater in collectivism and gender role traditionalism than Americans. The purpose of the present study was to examine whether these differences explained further cultural differences in romantic beliefs, traditional mate preferences, and anticipation of future difficulties in marital life. Results revealed that Indians reported greater collectivism than Americans and, in turn, held stronger romantic beliefs. Additionally, Indians’ greater collectivism and endorsement of more traditional gender roles in part predicted their preferences for a marital partner possessing traditional characteristics, and fully accounted for their heightened concerns about encountering future difficulties in marital life. These results shed light on the processes underlying cultural differences in relationship attitudes and preferences, and point to culture-specific therapies to enhance marital functioning

    The Long Noncoding RNA CCAT2 Induces Chromosomal Instability Through BOP1-AURKB Signaling

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    BACKGROUND &amp; AIMS: Chromosomal instability (CIN) is a carcinogenesis event that promotes metastasis and resistance to therapy by unclear mechanisms. Expression of the colon cancer-associated transcript 2 gene (CCAT2), which encodes a long noncoding RNA (lncRNA), associates with CIN, but little is known about how CCAT2 lncRNA regulates this cancer enabling characteristic.METHODS: We performed cytogenetic analysis of colorectal cancer (CRC) cell lines (HCT116, KM12C/SM, and HT29) overexpressing CCAT2 and colon organoids from C57BL/6N mice with the CCAT2 transgene and without (controls). CRC cells were also analyzed by immunofluorescence microscopy, gamma-H2AX, and senescence assays. CCAT2 transgene and control mice were given azoxymethane and dextran sulfate sodium to induce colon tumors. We performed gene expression array and mass spectrometry to detect downstream targets of CCAT2 lncRNA. We characterized interactions between CCAT2 with downstream proteins using MS2 pull-down, RNA immunoprecipitation, and selective 2'-hydroxyl acylation analyzed by primer extension analyses. Downstream proteins were overexpressed in CRC cells and analyzed for CIN. Gene expression levels were measured in CRC and non-tumor tissues from 5 cohorts, comprising more than 900 patients.RESULTS: High expression of CCAT2 induced CIN in CRC cell lines and increased resistance to 5-fluorouracil and oxaliplatin. Mice that expressed the CCAT2 transgene developed chromosome abnormalities, and colon organoids derived from crypt cells of these mice had a higher percentage of chromosome abnormalities compared with organoids from control mice. The transgenic mice given azoxymethane and dextran sulfate sodium developed more and larger colon polyps than control mice given these agents. Microarray analysis and mass spectrometry indicated that expression of CCAT2 increased expression of genes involved in ribosome biogenesis and protein synthesis. CCAT2 lncRNA interacted directly with and stabilized BOP1 ribosomal biogenesis factor (BOP1). CCAT2 also increased expression of MYC, which activated expression of BOP1. Overexpression of BOP1 in CRC cell lines resulted in chromosomal missegregation errors, and increased colony formation, and invasiveness, whereas BOP1 knockdown reduced viability. BOP1 promoted CIN by increasing the active form of aurora kinase B, which regulates chromosomal segregation. BOP1 was overexpressed in polyp tissues from CCAT2 transgenic mice compared with healthy tissue. CCAT2 lncRNA and BOP1 mRNA or protein were all increased in microsatellite stable tumors (characterized by CIN), but not in tumors with microsatellite instability compared with nontumor tissues. Increased levels of CCAT2 lncRNA and BOP1 mRNA correlated with each other and with shorter survival times of patients.CONCLUSIONS: We found that overexpression of CCAT2 in colon cells promotes CIN and carcinogenesis by stabilizing and inducing expression of BOP1 an activator of aurora kinase B. Strategies to target this pathway might be developed for treatment of patients with microsatellite stable colorectal tumors

    Graphene Schottky diodes: an experimental review of the rectifying graphene/semiconductor heterojunction

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    In the past decade graphene has been one of the most studied material for several unique and excellent properties. Due to its two dimensional nature, physical and chemical properties and ease of manipulation, graphene offers the possibility of integration with the exiting semiconductor technology for next-generation electronic and sensing devices. In this context, the understanding of the graphene/semiconductor interface is of great importance since it can constitute a versatile standalone device as well as the building-block of more advanced electronic systems. Since graphene was brought to the attention of the scientific community in 2004, the device research has been focused on the more complex graphene transistors, while the graphene/semiconductor junction, despite its importance, has started to be the subject of systematic investigation only recently. As a result, a thorough understanding of the physics and the potentialities of this device is still missing. The studies of the past few years have demonstrated that graphene can form junctions with 3D or 2D semiconducting materials which have rectifying characteristics and behave as excellent Schottky diodes. The main novelty of these devices is the tunable Schottky barrier height, a feature which makes the graphene/semiconductor junction a great platform for the study of interface transport mechanisms as well as for applications in photo-detection, high-speed communications, solar cells, chemical and biological sensing, etc. In this paper, we review the state-of-the art of the research on graphene/semiconductor junctions, the attempts towards a modeling and the most promising applications.Comment: 85 pages. Review articl

    THEMIS: A Parameter Estimation Framework for the Event Horizon Telescope

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    The Event Horizon Telescope (EHT) provides the unprecedented ability to directly resolve the structure and dynamics of black hole emission regions on scales smaller than their horizons. This has the potential to critically probe the mechanisms by which black holes accrete and launch outflows, and the structure of supermassive black hole spacetimes. However, accessing this information is a formidable analysis challenge for two reasons. First, the EHT natively produces a variety of data types that encode information about the image structure in nontrivial ways; these are subject to a variety of systematic effects associated with very long baseline interferometry and are supplemented by a wide variety of auxiliary data on the primary EHT targets from decades of other observations. Second, models of the emission regions and their interaction with the black hole are complex, highly uncertain, and computationally expensive to construct. As a result, the scientific utilization of EHT observations requires a flexible, extensible, and powerful analysis framework. We present such a framework, Themis, which defines a set of interfaces between models, data, and sampling algorithms that facilitates future development. We describe the design and currently existing components of Themis, how Themis has been validated thus far, and present additional analyses made possible by Themis that illustrate its capabilities. Importantly, we demonstrate that Themis is able to reproduce prior EHT analyses, extend these, and do so in a computationally efficient manner that can efficiently exploit modern high-performance computing facilities. Themis has already been used extensively in the scientific analysis and interpretation of the first EHT observations of M87

    SYMBA: An end-to-end VLBI synthetic data generation pipeline: Simulating Event Horizon Telescope observations of M 87

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    Context. Realistic synthetic observations of theoretical source models are essential for our understanding of real observational data. In using synthetic data, one can verify the extent to which source parameters can be recovered and evaluate how various data corruption effects can be calibrated. These studies are the most important when proposing observations of new sources, in the characterization of the capabilities of new or upgraded instruments, and when verifying model-based theoretical predictions in a direct comparison with observational data. Aims. We present the SYnthetic Measurement creator for long Baseline Arrays (SYMBA), a novel synthetic data generation pipeline for Very Long Baseline Interferometry (VLBI) observations. SYMBA takes into account several realistic atmospheric, instrumental, and calibration effects. Methods. We used SYMBA to create synthetic observations for the Event Horizon Telescope (EHT), a millimetre VLBI array, which has recently captured the first image of a black hole shadow. After testing SYMBA with simple source and corruption models, we study the importance of including all corruption and calibration effects, compared to the addition of thermal noise only. Using synthetic data based on two example general relativistic magnetohydrodynamics (GRMHD) model images of M 87, we performed case studies to assess the image quality that can be obtained with the current and future EHT array for different weather conditions. Results. Our synthetic observations show that the effects of atmospheric and instrumental corruptions on the measured visibilities are significant. Despite these effects, we demonstrate how the overall structure of our GRMHD source models can be recovered robustly with the EHT2017 array after performing calibration steps, which include fringe fitting, a priori amplitude and network calibration, and self-calibration. With the planned addition of new stations to the EHT array in the coming years, images could be reconstructed with higher angular resolution and dynamic range. In our case study, these improvements allowed for a distinction between a thermal and a non-thermal GRMHD model based on salient features in reconstructed images

    Monitoring the Morphology of M87* in 2009–2017 with the Event Horizon Telescope

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    The Event Horizon Telescope (EHT) has recently delivered the first resolved images of M87*, the supermassive black hole in the center of the M87 galaxy. These images were produced using 230 GHz observations performed in 2017 April. Additional observations are required to investigate the persistence of the primary image feature—a ring with azimuthal brightness asymmetry—and to quantify the image variability on event horizon scales. To address this need, we analyze M87* data collected with prototype EHT arrays in 2009, 2011, 2012, and 2013. While these observations do not contain enough information to produce images, they are sufficient to constrain simple geometric models. We develop a modeling approach based on the framework utilized for the 2017 EHT data analysis and validate our procedures using synthetic data. Applying the same approach to the observational data sets, we find the M87* morphology in 2009–2017 to be consistent with a persistent asymmetric ring of ~40 μas diameter. The position angle of the peak intensity varies in time. In particular, we find a significant difference between the position angle measured in 2013 and 2017. These variations are in broad agreement with predictions of a subset of general relativistic magnetohydrodynamic simulations. We show that quantifying the variability across multiple observational epochs has the potential to constrain the physical properties of the source, such as the accretion state or the black hole spin

    First M87 Event Horizon Telescope Results. VI. The Shadow and Mass of the Central Black Hole

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    We present measurements of the properties of the central radio source in M87 using Event Horizon Telescope data obtained during the 2017 campaign. We develop and fit geometric crescent models (asymmetric rings with interior brightness depressions) using two independent sampling algorithms that consider distinct representations of the visibility data. We show that the crescent family of models is statistically preferred over other comparably complex geometric models that we explore. We calibrate the geometric model parameters using general relativistic magnetohydrodynamic (GRMHD) models of the emission region and estimate physical properties of the source. We further fit images generated from GRMHD models directly to the data. We compare the derived emission region and black hole parameters from these analyses with those recovered from reconstructed images. There is a remarkable consistency among all methods and data sets. We find that >50% of the total flux at arcsecond scales comes from near the horizon, and that the emission is dramatically suppressed interior to this region by a factor >10, providing direct evidence of the predicted shadow of a black hole. Across all methods, we measure a crescent diameter of 42 +/- 3 mu as and constrain its fractional width to b
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