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- Marinucci, A., et al.
(författare)
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Polarization constraints on the X-ray corona in Seyfert Galaxies : MCG-05-23-16
- 2022
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 516:4, s. 5907-5913
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Tidskriftsartikel (refereegranskat)abstract
- We report on the first observation of a radio-quiet active galactic nucleus (AGN) in polarized X-rays: the Seyfert 1.9 galaxy MCG-05-23-16. This source was pointed at with the Imaging X-ray Polarimetry Explorer (IXPE) starting on 2022 May 14 for a net observing time of 486 ks, simultaneously with XMM-Newton (58 ks) and NuSTAR (83 ks). A polarization degree Π smaller than 4.7 per cent (at the 99 per cent confidence level) is derived in the 2–8 keV energy range, where emission is dominated by the primary component ascribed to the hot corona. The broad-band spectrum, inferred from a simultaneous fit to the IXPE, NuSTAR, and XMM-Newton data, is well reproduced by a power law with photon index Γ = 1.85 ± 0.01 and a high-energy cutoff EC = 120 ± 15 keV. A comparison with Monte Carlo simulations shows that a lamp-post and a conical geometry of the corona are consistent with the observed upper limit, a slab geometry is allowed only if the inclination angle of the system is less than 50°.
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- Novak, R., et al.
(författare)
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Robotic fluidic coupling and interrogation of multiple vascularized organ chips
- 2020
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Ingår i: Nature Biomedical Engineering. - : Nature Research. - 2157-846X.
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Tidskriftsartikel (refereegranskat)abstract
- Organ chips can recapitulate organ-level (patho)physiology, yet pharmacokinetic and pharmacodynamic analyses require multi-organ systems linked by vascular perfusion. Here, we describe an ‘interrogator’ that employs liquid-handling robotics, custom software and an integrated mobile microscope for the automated culture, perfusion, medium addition, fluidic linking, sample collection and in situ microscopy imaging of up to ten organ chips inside a standard tissue-culture incubator. The robotic interrogator maintained the viability and organ-specific functions of eight vascularized, two-channel organ chips (intestine, liver, kidney, heart, lung, skin, blood–brain barrier and brain) for 3 weeks in culture when intermittently fluidically coupled via a common blood substitute through their reservoirs of medium and endothelium-lined vascular channels. We used the robotic interrogator and a physiological multicompartmental reduced-order model of the experimental system to quantitatively predict the distribution of an inulin tracer perfused through the multi-organ human-body-on-chips. The automated culture system enables the imaging of cells in the organ chips and the repeated sampling of both the vascular and interstitial compartments without compromising fluidic coupling.
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- Soda, T., et al.
(författare)
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International Consortium on the Genetics of Electroconvulsive Therapy and Severe Depressive Disorders (Gen-ECT-ic)
- 2020
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Ingår i: European Archives of Psychiatry and Clinical Neuroscience. - : Springer Science and Business Media LLC. - 0940-1334 .- 1433-8491. ; 270:7, s. 921-932
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Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association studies have demonstrated that the genetic burden associated with depression correlates with depression severity. Therefore, conducting genetic studies of patients at the most severe end of the depressive disorder spectrum, those with treatment-resistant depression and who are prescribed electroconvulsive therapy (ECT), could lead to a better understanding of the genetic underpinnings of depression. Despite ECT being one of the most effective forms of treatment for severe depressive disorders, it is usually placed at the end of treatment algorithms of current guidelines. This is perhaps because ECT has controlled risk and logistical demands including use of general anaesthesia and muscle relaxants and side-effects such as short-term memory impairment. Better understanding of the genetics and biology of ECT response and of cognitive side-effects could lead to more personalized treatment decisions. To enhance the understanding of the genomics of severe depression and ECT response, researchers and ECT providers from around the world and from various depression or ECT networks, but not limited to, such as the Psychiatric Genomics Consortium, the Clinical Alliance and Research in ECT, and the National Network of Depression Centers have formed the Genetics of ECT International Consortium (Gen-ECT-ic). Gen-ECT-ic will organize the largest clinical and genetic collection to date to study the genomics of severe depressive disorders and response to ECT, aiming for 30,000 patients worldwide using a GWAS approach. At this stage it will be the largest genomic study on treatment response in depression. Retrospective data abstraction and prospective data collection will be facilitated by a uniform data collection approach that is flexible and will incorporate data from many clinical practices. Gen-ECT-ic invites all ECT providers and researchers to join its efforts.
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- Goddi, Ciriaco, et al.
(författare)
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Polarimetric Properties of Event Horizon Telescope Targets from ALMA
- 2021
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 910:1
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Tidskriftsartikel (refereegranskat)abstract
- We present the results from a full polarization study carried out with the Atacama Large Millimeter/submillimeter Array (ALMA) during the first Very Long Baseline Interferometry (VLBI) campaign, which was conducted in 2017 April in the lambda 3 mm and lambda 1.3 mm bands, in concert with the Global mm-VLBI Array (GMVA) and the Event Horizon Telescope (EHT), respectively. We determine the polarization and Faraday properties of all VLBI targets, including Sgr A*, M87, and a dozen radio-loud active galactic nuclei (AGNs), in the two bands at several epochs in a time window of 10 days. We detect high linear polarization fractions (2%-15%) and large rotation measures (RM > 10(3.3)-10(5.5) rad m(-2)), confirming the trends of previous AGN studies at millimeter wavelengths. We find that blazars are more strongly polarized than other AGNs in the sample, while exhibiting (on average) order-of-magnitude lower RM values, consistent with the AGN viewing angle unification scheme. For Sgr A* we report a mean RM of (-4.2 0.3) x 10(5) rad m(-2) at 1.3 mm, consistent with measurements over the past decade and, for the first time, an RM of (-2.1 0.1) x 10(5) rad m(-2) at 3 mm, suggesting that about half of the Faraday rotation at 1.3 mm may occur between the 3 mm photosphere and the 1.3 mm source. We also report the first unambiguous measurement of RM toward the M87 nucleus at millimeter wavelengths, which undergoes significant changes in magnitude and sign reversals on a one year timescale, spanning the range from -1.2 to 0.3 x 10(5) rad m(-2) at 3 mm and -4.1 to 1.5 x 10(5) rad m(-2) at 1.3 mm. Given this time variability, we argue that, unlike the case of Sgr A*, the RM in M87 does not provide an accurate estimate of the mass accretion rate onto the black hole. We put forward a two-component model, comprised of a variable compact region and a static extended region, that can simultaneously explain the polarimetric properties observed by both the EHT (on horizon scales) and ALMA (which observes the combined emission from both components). These measurements provide critical constraints for the calibration, analysis, and interpretation of simultaneously obtained VLBI data with the EHT and GMVA.
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- Herland, Anna, et al.
(författare)
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Quantitative prediction of human pharmacokinetic responses to drugs via fluidically coupled vascularized organ chips
- 2020
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Ingår i: Nature Biomedical Engineering. - : Springer Science and Business Media LLC. - 2157-846X. ; 4:4, s. 421-436
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Tidskriftsartikel (refereegranskat)abstract
- Analyses of drug pharmacokinetics (PKs) and pharmacodynamics (PDs) performed in animals are often not predictive of drug PKs and PDs in humans, and in vitro PK and PD modelling does not provide quantitative PK parameters. Here, we show that physiological PK modelling of first-pass drug absorption, metabolism and excretion in humans—using computationally scaled data from multiple fluidically linked two-channel organ chips—predicts PK parameters for orally administered nicotine (using gut, liver and kidney chips) and for intravenously injected cisplatin (using coupled bone marrow, liver and kidney chips). The chips are linked through sequential robotic liquid transfers of a common blood substitute by their endothelium-lined channels (as reported by Novak et al. in an associated Article) and share an arteriovenous fluid-mixing reservoir. We also show that predictions of cisplatin PDs match previously reported patient data. The quantitative in-vitro-to-in-vivo translation of PK and PD parameters and the prediction of drug absorption, distribution, metabolism, excretion and toxicity through fluidically coupled organ chips may improve the design of drug-administration regimens for phase-I clinical trials.
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- Tatovic, D, et al.
(författare)
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Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes
- 2022
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Ingår i: Immunotherapy Advances. - : Oxford University Press (OUP). - 2732-4303. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Antigen-specific immunotherapy is an immunomodulatory strategy for autoimmune diseases, such as type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune β-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human proinsulin peptide C19-A3 (known for its positive safety profile) was conjugated to ultrasmall gold nanoparticles (GNPs), an attractive drug delivery platform due to the potential anti-inflammatory properties of gold. We hypothesised that microneedle intradermal delivery of C19-A3 GNP may improve peptide pharmacokinetics and induce tolerogenic immunomodulation and proceeded to evaluate its safety and feasibility in a first-in-human trial. Allowing for the limitation of the small number of participants, intradermal administration of C19-A3 GNP appears safe and well tolerated in participants with type 1 diabetes. The associated prolonged skin retention of C19-A3 GNP after intradermal administration offers a number of possibilities to enhance its tolerogenic potential, which should be explored in future studies.
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