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| 2. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 3. |
- Abolhassani, Hassan, et al.
(författare)
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Genetic and immunologic evaluation of children with inborn errors of immunity and severe or critical COVID-19
- 2022
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 150:5, s. 1059-1073
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Tidskriftsartikel (refereegranskat)abstract
- Background: Most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals are asymptomatic or only exhibit mild disease. In about 10% of cases, the infection leads to hypoxemic pneumonia, although it is much more rare in children. Objective: We evaluated 31 young patients aged 0.5 to 19 years who had preexisting inborn errors of immunity (IEI) but lacked a molecular diagnosis and were later diagnosed with coronavirus disease 2019 (COVID-19) complications. Methods: Genetic evaluation by whole-exome sequencing was performed in all patients. SARS-CoV-2-specific antibodies, autoantibodies against type I IFN (IFN-I), and inflammatory factors in plasma were measured. We also reviewed COVID-19 disease severity/outcome in reported IEI patients. Results: A potential genetic cause of the IEI was identified in 28 patients (90.3%), including mutations that may affect IFN signaling, T- and B-cell function, the inflammasome, and the complement system. From tested patients 65.5% had detectable virus-specific antibodies, and 6.8% had autoantibodies neutralizing IFN-I. Five patients (16.1%) fulfilled the diagnostic criteria of multisystem inflammatory syndrome in children. Eleven patients (35.4%) died of COVID-19 complications. All together, at least 381 IEI children with COVID-19 have been reported in the literature to date. Although many patients with asymptomatic or mild disease may not have been reported, severe presentation of COVID-19 was observed in 23.6% of the published cases, and the mortality rate was 8.7%. Conclusions: Young patients with preexisting IEI may have higher mortality than children without IEI when infected with SARS-CoV-2. Elucidating the genetic basis of IEI patients with severe/critical COVID-19 may help to develop better strategies for prevention and treatment of severe COVID-19 disease and complications in pediatric patients.
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| 4. |
- Abolhassani, Hassan, et al.
(författare)
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Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome
- 2022
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Ingår i: Journal of Clinical Immunology. - : Springer Nature. - 0271-9142 .- 1573-2592. ; 42:3, s. 471-483
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Tidskriftsartikel (refereegranskat)abstract
- Background Inborn errors of immunity (IEI) and autoantibodies to type I interferons (IFNs) underlie critical COVID-19 pneumonia in at least 15% of the patients, while the causes of multisystem inflammatory syndrome in children (MIS-C) remain elusive. Objectives To detect causal genetic variants in very rare cases with concomitant critical COVID-19 pneumonia and MIS-C. Methods Whole exome sequencing was performed, and the impact of candidate gene variants was investigated. Plasma levels of cytokines, specific antibodies against the virus, and autoantibodies against type I IFNs were also measured. Results We report a 3-year-old child who died on day 56 of SARS-CoV-2 infection with an unusual clinical presentation, combining both critical COVID-19 pneumonia and MIS-C. We identified a large, homozygous loss-of-function deletion in IFNAR1, underlying autosomal recessive IFNAR1 deficiency. Conclusions Our findings confirm that impaired type I IFN immunity can underlie critical COVID-19 pneumonia, while suggesting that it can also unexpectedly underlie concomitant MIS-C. Our report further raises the possibility that inherited or acquired dysregulation of type I IFN immunity might contribute to MIS-C in other patients.
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| 5. |
- Abolhassani, Hassan, et al.
(författare)
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X-Linked TLR7 Deficiency Underlies Critical COVID-19 Pneumonia in a Male Patient with Ataxia-Telangiectasia
- 2022
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Ingår i: Journal of Clinical Immunology. - : Springer Science and Business Media LLC. - 0271-9142 .- 1573-2592. ; 42:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Background Coronavirus disease 2019 (COVID-19) exhibits a wide spectrum of clinical manifestations, ranging from asymptomatic to critical conditions. Understanding the mechanism underlying life-threatening COVID-19 is instrumental for disease prevention and treatment in individuals with a high risk.Objectives We aimed to identify the genetic cause for critical COVID-19 pneumonia in a patient with a preexisting inborn error of immunity (IEI).Methods Serum levels of specific antibodies against the virus and autoantibodies against type I interferons (IFNs) were measured. Whole exome sequencing was performed, and the impacts of candidate gene variants were investigated. We also evaluated 247 ataxia-telangiectasia (A-T) patients in the Iranian IEI registry.Results We report a 7-year-old Iranian boy with a preexisting hyper IgM syndrome who developed critical COVID-19 pneumonia. IgM only specific COVID-19 immune response was detected but no autoantibodies against type I IFN were observed. A homozygous deleterious mutation in the ATM gene was identified, which together with his antibody deficiency, radiosensitivity, and neurological signs, established a diagnosis of A-T. Among the 247 A-T patients evaluated, 36 had SARS-CoV-2 infection, but all had mild symptoms or were asymptomatic except the index patient. A hemizygous deleterious mutation in the TLR7 gene was subsequently identified in the patient.Conclusions We report a unique IEI patient with combined ATM and TLR7 deficiencies. The two genetic defects underlie A-T and critical COVID-19 in this patient, respectively.
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| 6. |
- Akiyama, Kazunori, et al.
(författare)
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First M87 Event Horizon Telescope Results. IX. Detection of Near-horizon Circular Polarization
- 2023
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Ingår i: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 957:2
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Tidskriftsartikel (refereegranskat)abstract
- Event Horizon Telescope (EHT) observations have revealed a bright ring of emission around the supermassive black hole at the center of the M87 galaxy. EHT images in linear polarization have further identified a coherent spiral pattern around the black hole, produced from ordered magnetic fields threading the emitting plasma. Here we present the first analysis of circular polarization using EHT data, acquired in 2017, which can potentially provide additional insights into the magnetic fields and plasma composition near the black hole. Interferometric closure quantities provide convincing evidence for the presence of circularly polarized emission on event-horizon scales. We produce images of the circular polarization using both traditional and newly developed methods. All methods find a moderate level of resolved circular polarization across the image (〈|v|〉 < 3.7%), consistent with the low image-integrated circular polarization fraction measured by the Atacama Large Millimeter/submillimeter Array (|vint| < 1%). Despite this broad agreement, the methods show substantial variation in the morphology of the circularly polarized emission, indicating that our conclusions are strongly dependent on the imaging assumptions because of the limited baseline coverage, uncertain telescope gain calibration, and weakly polarized signal. We include this upper limit in an updated comparison to general relativistic magnetohydrodynamic simulation models. This analysis reinforces the previously reported preference for magnetically arrested accretion flow models. We find that most simulations naturally produce a low level of circular polarization consistent with our upper limit and that Faraday conversion is likely the dominant production mechanism for circular polarization at 230 GHz in M87*
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| 7. |
- Akiyama, Kazunori, et al.
(författare)
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First Sagittarius A∗ Event Horizon Telescope Results. VII. Polarization of the Ring
- 2024
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Ingår i: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 964:2
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Tidskriftsartikel (refereegranskat)abstract
- The Event Horizon Telescope observed the horizon-scale synchrotron emission region around the Galactic center supermassive black hole, Sagittarius A∗ (Sgr A∗), in 2017. These observations revealed a bright, thick ring morphology with a diameter of 51.8 ± 2.3 μas and modest azimuthal brightness asymmetry, consistent with the expected appearance of a black hole with mass M≈ 4 × 106 M⊙. From these observations, we present the first resolved linear and circular polarimetric images of Sgr A∗. The linear polarization images demonstrate that the emission ring is highly polarized, exhibiting a prominent spiral electric vector polarization angle pattern with a peak fractional polarization of ∼40% in the western portion of the ring. The circular polarization images feature a modestly (∼5%°-10%) polarized dipole structure along the emission ring, with negative circular polarization in the western region and positive circular polarization in the eastern region, although our methods exhibit stronger disagreement than for linear polarization. We analyze the data using multiple independent imaging and modeling methods, each of which is validated using a standardized suite of synthetic data sets. While the detailed spatial distribution of the linear polarization along the ring remains uncertain owing to the intrinsic variability of the source, the spiraling polarization structure is robust to methodological choices. The degree and orientation of the linear polarization provide stringent constraints for the black hole and its surrounding magnetic fields, which we discuss in an accompanying publication.
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| 8. |
- Akiyama, Kazunori, et al.
(författare)
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First Sagittarius A∗ Event Horizon Telescope Results. VIII. Physical Interpretation of the Polarized Ring
- 2024
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Ingår i: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 964:2
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Tidskriftsartikel (refereegranskat)abstract
- In a companion paper, we present the first spatially resolved polarized image of Sagittarius A∗ on event horizon scales, captured using the Event Horizon Telescope, a global very long baseline interferometric array operating at a wavelength of 1.3 mm. Here we interpret this image using both simple analytic models and numerical general relativistic magnetohydrodynamic (GRMHD) simulations. The large spatially resolved linear polarization fraction (24%-28%, peaking at ∼40%) is the most stringent constraint on parameter space, disfavoring models that are too Faraday depolarized. Similar to our studies of M87∗, polarimetric constraints reinforce a preference for GRMHD models with dynamically important magnetic fields. Although the spiral morphology of the polarization pattern is known to constrain the spin and inclination angle, the time-variable rotation measure (RM) of Sgr A∗ (equivalent to ≈ 46° ± 12° rotation at 228 GHz) limits its present utility as a constraint. If we attribute the RM to internal Faraday rotation, then the motion of accreting material is inferred to be counterclockwise, contrary to inferences based on historical polarized flares, and no model satisfies all polarimetric and total intensity constraints. On the other hand, if we attribute the mean RM to an external Faraday screen, then the motion of accreting material is inferred to be clockwise, and one model passes all applied total intensity and polarimetric constraints: a model with strong magnetic fields, a spin parameter of 0.94, and an inclination of 150°. We discuss how future 345 GHz and dynamical imaging will mitigate our present uncertainties and provide additional constraints on the black hole and its accretion flow.
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| 9. |
- Akiyama, Kazunori, et al.
(författare)
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The persistent shadow of the supermassive black hole of M 87: I. Observations, calibration, imaging, and analysis*
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 681
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Tidskriftsartikel (refereegranskat)abstract
- In April 2019, the Event Horizon Telescope (EHT) Collaboration reported the first-ever event-horizon-scale images of a black hole, resolving the central compact radio source in the giant elliptical galaxy M 87. These images reveal a ring with a southerly brightness distribution and a diameter of ∼42 μas, consistent with the predicted size and shape of a shadow produced by the gravitationally lensed emission around a supermassive black hole. These results were obtained as part of the April 2017 EHT observation campaign, using a global very long baseline interferometric radio array operating at a wavelength of 1.3 mm. Here, we present results based on the second EHT observing campaign, taking place in April 2018 with an improved array, wider frequency coverage, and increased bandwidth. In particular, the additional baselines provided by the Greenland telescope improved the coverage of the array. Multiyear EHT observations provide independent snapshots of the horizon-scale emission, allowing us to confirm the persistence, size, and shape of the black hole shadow, and constrain the intrinsic structural variability of the accretion flow. We have confirmed the presence of an asymmetric ring structure, brighter in the southwest, with a median diameter of 43.3-3.1+1.5 μas. The diameter of the 2018 ring is remarkably consistent with the diameter obtained from the previous 2017 observations. On the other hand, the position angle of the brightness asymmetry in 2018 is shifted by about 30 relative to 2017. The perennial persistence of the ring and its diameter robustly support the interpretation that the ring is formed by lensed emission surrounding a Kerr black hole with a mass ∼6.5× 109M. The significant change in the ring brightness asymmetry implies a spin axis that is more consistent with the position angle of the large-scale jet.
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| 10. |
- Algaba, Juan-Carlos, et al.
(författare)
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Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign
- 2021
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
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Forskningsöversikt (refereegranskat)abstract
- In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded.
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