404 research outputs found

    Turbulence Properties of Interplanetary Coronal Mass Ejections in the Inner Heliosphere: Dependence on Proton Beta and Flux Rope Structure

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    Interplanetary coronal mass ejections (ICMEs) have low proton beta across a broad range of heliocentric distances and a magnetic flux rope structure at large scales, making them a unique environment for studying solar wind fluctuations. Power spectra of magnetic field fluctuations in 28 ICMEs observed between 0.25 and 0.95 au by Solar Orbiter and Parker Solar Probe have been examined. At large scales, the spectra were dominated by power contained in the flux ropes. Subtraction of the background flux rope fields reduced the mean spectral index from −5/3-5/3 to −3/2-3/2 at kdi≤10−3kd_i \leq 10^{-3}. Rope subtraction also revealed shorter correlation lengths in the magnetic field. The spectral index was typically near −5/3-5/3 in the inertial range at all radial distances regardless of rope subtraction, and steepened to values consistently below −3-3 with transition to kinetic scales. The high-frequency break point terminating the inertial range evolved approximately linearly with radial distance and was closer in scale to the proton inertial length than the proton gyroscale, as expected for plasma at low proton beta. Magnetic compressibility at inertial scales did not show any significant correlation with radial distance, in contrast to the solar wind generally. In ICMEs, the distinctive spectral properties at injection scales appear mostly determined by the global flux rope structure while transition-kinetic properties are more influenced by the low proton beta; the intervening inertial range appears independent of both ICME features, indicative of a system-independent scaling of the turbulence.Comment: 12 pages, 5 figures; accepted for publication in the Astrophysical Journal Letters 2023 September 2

    PTEN and DNA-PK determine sensitivity and recovery in response to WEE1 inhibition in human breast cancer

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    Inhibition of WEE1 kinase by AZD1775 has shown promising results in clinical cancer trials, but markers predicting AZD1775 response are lacking. Here we analysed AZD1775 response in a panel of human breast cancer (BC) cell lines by global proteome/transcriptome profiling and identified two groups of basal-like BC (BLBCs): ‘PTEN low’ BLBCs were highly sensitive to AZD1775 and failed to recover following removal of AZD1775, while ‘PTEN high’ BLBCs recovered. AZD1775 induced phosphorylation of DNA-PK, protecting cells from replication-associated DNA damage and promoting cellular recovery. Deletion of DNA-PK or PTEN, or inhibition of DNA-PK sensitized recovering BLBCs to AZD1775 by abrogating replication arrest, allowing replication despite DNA damage. This was linked to reduced CHK1 activation, increased cyclin E levels and apoptosis. In conclusion, we identified PTEN and DNA-PK as essential regulators of replication checkpoint arrest in response to AZD1775 and defined PTEN as a promising biomarker for efficient WEE1 cancer therapy

    Evaluating the performance of five different chemical ionization techniques for detecting gaseous oxygenated organic species

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    The impact of aerosols on climate and air quality remains poorly understood due to multiple factors. One of the current limitations is the incomplete understanding of the contribution of oxygenated products, generated from the gas-phase oxidation of volatile organic compounds (VOCs), to aerosol formation. Indeed, atmospheric gaseous chemical processes yield thousands of (highly) oxygenated species, spanning a wide range of chemical formulas, functional groups and, consequently, volatilities. While recent mass spectrometric developments have allowed extensive on-line detection of a myriad of oxygenated organic species, playing a central role in atmospheric chemistry, the detailed quantification and characterization of this diverse group of compounds remains extremely challenging. To address this challenge, we evaluated the capability of current state-of-the-art mass spectrometers equipped with different chemical ionization sources to detect the oxidation products formed from alpha-Pinene ozonolysis under various conditions. Five different mass spectrometers were deployed simultaneously for a chamber study. Two chemical ionization atmospheric pressure interface time-of-flight mass spectrometers (CI-APi-TOF) with nitrate and amine reagent ion chemistries and an iodide chemical ionization time-of-flight mass spectrometer (TOF-CIMS) were used. Additionally, a proton transfer reaction time-of-flight mass spectrometer (PTR-TOF 8000) and a new "vocus" PTR-TOF were also deployed. In the current study, we compared around 1000 different compounds between each of the five instruments, with the aim of determining which oxygenated VOCs (OVOCs) the different methods were sensitive to and identifying regions where two or more instruments were able to detect species with similar molecular formulae. We utilized a large variability in conditions (including different VOCs, ozone, NOx and OH scavenger concentrations) in our newly constructed atmospheric simulation chamber for a comprehensive correlation analysis between all instruments. This analysis, combined with estimated concentrations for identified molecules in each instrument, yielded both expected and surprising results. As anticipated based on earlier studies, the PTR instruments were the only ones able to measure the precursor VOC, the iodide TOF-CIMS efficiently detected many semi-volatile organic compounds (SVOCs) with three to five oxygen atoms, and the nitrate CI-APi-TOF was mainly sensitive to highly oxygenated organic (O > 5) molecules (HOMs). In addition, the vocus showed good agreement with the iodide TOF-CIMS for the SVOC, including a range of organonitrates. The amine CI-APi-TOF agreed well with the nitrate CI-APi-TOF for HOM dimers. However, the loadings in our experiments caused the amine reagent ion to be considerably depleted, causing nonlinear responses for monomers. This study explores and highlights both benefits and limitations of currently available chemical ionization mass spectrometry instrumentation for characterizing the wide variety of OVOCs in the atmosphere. While specifically shown for the case of alpha-Pinene ozonolysis, we expect our general findings to also be valid for a wide range of other VOC-oxidant systems. As discussed in this study, no single instrument configuration can be deemed better or worse than the others, as the optimal instrument for a particular study ultimately depends on the specific target of the study.Peer reviewe

    Non-tuberculous Mycobacteria can Cause Disseminated Mycobacteriosis in Cats

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    Mycobacteriosis caused by non-tuberculous mycobacteria (NTM) is a rising concern in human medicine both in immunocompromised and immunocompetent patients. In cats, mycobacteriosis caused by NTM is considered mostly to be a focal or dermal infection, with disseminated disease mostly caused by Mycobacterium avium. We describe three cases of disseminated mycobacteriosis in cats, caused by Mycobacterium malmoense, Mycobacterium branderi/shimoidei and M. avium, with no identified underlying immunosuppression. In all cases, extracellular mycobacteria were seen in the pulmonary epithelium, intestinal lumen and glomerular tufts, which could affect the shedding of the organism. The present study highlights the importance of mycobacteriosis as a differential even in immunocompetent animals. Considering the close relationship of owners and pets and the potential presence of free mycobacteria in secretions, cats should be considered as a possible environmental reservoir for mycobacteria. (C) 2018 Elsevier Ltd. All rights reserved.Peer reviewe

    The Arabidopsis NOT4A E3 ligase promotes PGR3 expression and regulates chloroplast translation

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    Chloroplast function requires the coordinated action of nuclear- and chloroplast-derived proteins, including several hundred nuclear-encoded pentatricopeptide repeat (PPR) proteins that regulate plastid mRNA metabolism. Despite their large number and importance, regulatory mechanisms controlling PPR expression are poorly understood. Here we show that the Arabidopsis NOT4A ubiquitin-ligase positively regulates the expression of PROTON GRADIENT REGULATION 3 (PGR3), a PPR protein required for translating several thylakoid-localised photosynthetic components and ribosome subunits within chloroplasts. Loss of NOT4A function leads to a strong depletion of cytochrome b6f and NAD(P)H dehydrogenase (NDH) complexes, as well as plastid 30 S ribosomes, which reduces mRNA translation and photosynthetic capacity, causing pale-yellow and slow-growth phenotypes. Quantitative transcriptome and proteome analysis of the not4a mutant reveal it lacks PGR3 expression, and that its molecular defects resemble those of a pgr3 mutant. Furthermore, we show that normal plastid function is restored to not4a through transgenic PGR3 expression. Our work identifies NOT4A as crucial for ensuring robust photosynthetic function during development and stress-response, through promoting PGR3 production and chloroplast translatio

    ERS International Congress 2020: highlights from the epidemiology and environment assembly

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    In this article, early career members of the Epidemiology and Environment Assembly of the European Respiratory Society (ERS) summarise a selection of five sessions from the ERS 2020 Virtual International Congress. The topics covered include risk factors for chronic respiratory diseases over the life course, from early life origins to occupational exposures in adulthood, and the interplay between these risk factors, including gene–environment interactions. Novel results were also presented on smoking prevention and potential risks of vaping. Finally, the challenges and opportunities for epidemiological and environmental research brought by the coronavirus disease 2019 (COVID-19) pandemic were a major topic of this year's congress

    Analysis of pancreas tissue in a child positive for islet cell antibodies

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    Conclusions/interpretation These observations suggest that positivity for ICA alone, even when lasting for more than 1 year, is not associated with inflammatory changes in the islets. However, it is most likely that the pancreatic islets were infected by an enterovirus in this child
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