| 1. |
- Boettcher, Thomas, et al.
(författare)
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The HADES mission concept : astrobiological survey of Jupiter's icy moon Europa
- 2009
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Ingår i: International Journal of Astrobiology. - 1473-5504 .- 1475-3006. ; 8:4, s. 321-329
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Tidskriftsartikel (refereegranskat)abstract
- The HADES Europa mission concept aims to provide a framework for an astrobiological in-depth investigation of the Jupiter moon Europa, relying on existing technologies and feasibility. This mission study proposes a system consisting of an orbiter, lander and cryobot as a platform for detailed exploration of Europa. While the orbiter will investigate the presence of a liquid ocean and characterize Europa's internal structure, the lander will survey local dynamics of the ice layer and the surface environment. The lander releases a cryobot, that melts into the ice, will sample the pristine subsurface and is expected to provide data on organic and gaseous content and putative bio-signatures. In summary, we present the scientific objectives for an astrobiological investigation of Europa, resulting in a mission concept with a detailed evaluation of scientific instrumentation, mission sequences, basic design of the spacecraft, technology needs and cost estimations.
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| 2. |
- Bolatto, Alberto D., et al.
(författare)
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ALMA Imaging of a Galactic Molecular Outflow in NGC 4945
- 2021
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 923:1
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Tidskriftsartikel (refereegranskat)abstract
- We present the ALMA detection of molecular outflowing gas in the central regions of NGC 4945, one of the nearest starbursts and also one of the nearest hosts of an active galactic nucleus (AGN). We detect four outflow plumes in CO J= 3 - 2 at similar to 0.3 resolution that appear to correspond to molecular gas located near the edges of the known ionized outflow cone and its (unobserved) counterpart behind the disk. The fastest and brightest of these plumes has emission reaching observed line-of-sight projected velocities of over 450 km s(-1) beyond systemic, equivalent to an estimated physical outflow velocity v greater than or similar to 600 km s(-1) for the fastest emission. Most of these plumes have corresponding emission in HCN or HCO + J= 4 - 3. We discuss a kinematic model for the outflow emission where the molecular gas has the geometry of the ionized gas cone and shares the rotation velocity of the galaxy when ejected. We use this model to explain the velocities we observe, constrain the physical speed of the ejected material, and account for the fraction of outflowing gas that is not detected due to confusion with the galaxy disk. We estimate a total molecular mass outflow rate (M) over dot(mol) similar to 20 M-circle dot yr(-1) flowing through a surface within 100 pc of the disk midplane, likely driven by a combination of the central starburst and AGN.
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| 3. |
- Emig, Kimberly L., et al.
(författare)
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Super Star Clusters in the Central Starburst of NGC 4945
- 2020
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 903:1
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Tidskriftsartikel (refereegranskat)abstract
- The nearby (3.8Mpc) galaxy NGC 4945 hosts a nuclear starburst and Seyfert type 2 active galactic nucleus (AGN). We use the Atacama Large Millimeter/submillimeter Array (ALMA) to image the 93 GHz (3.2 mm) free-free continuum and hydrogen recombination line emission (H40 alpha and H42 alpha) at 2.2 pc (0 12) resolution. Our observations reveal 27 bright, compact sources with FWHM sizes of 1.4-4.0 pc, which we identify as candidate super star clusters. Recombination line emission, tracing the ionizing photon rate of the candidate clusters, is detected in 15 sources, six of which have a significant synchrotron component to the 93 GHz continuum. Adopting an age of similar to 5Myr, the stellar masses implied by the ionizing photon luminosities are log(10) (M*/M-circle dot) approximate to 4.7-6.1. We fit a slope to the cluster mass distribution and find beta = -1.8 +/-.0.4. The gas masses associated with these clusters, derived from the dust continuum at 350 GHz, are typically an order of magnitude lower than the stellar mass. These candidate clusters appear to have already converted a large fraction of their dense natal material into stars and, given their small freefall times of similar to 0.05 Myr, are surviving an early volatile phase. We identify a pointlike source in 93 GHz continuum emission that is presumed to be the AGN. We do not detect recombination line emission from the AGN and place an upper limit on the ionizing photons that leak into the starburst region of Q(0).<.10(52) s(-1).
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| 4. |
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| 5. |
- Levy, Rebecca C., et al.
(författare)
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Outflows from Super Star Clusters in the Central Starburst of NGC 253
- 2021
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 912:1
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Tidskriftsartikel (refereegranskat)abstract
- Young massive clusters play an important role in the evolution of their host galaxies, and feedback from the high-mass stars in these clusters can have profound effects on the surrounding interstellar medium. The nuclear starburst in the nearby galaxy NGC 253 at a distance of 3.5 Mpc is a key laboratory in which to study star formation in an extreme environment. Previous high-resolution (1.9 pc) dust continuum observations from the Atacama Large Millimeter/submillimeter Array (ALMA) discovered 14 compact, massive super star clusters (SSCs) still in formation. We present here ALMA data at 350 GHz with 28 mas (0.5 pc) resolution. We detect blueshifted absorption and redshifted emission (P-Cygni profiles) toward three of these SSCs in multiple lines, including CS 7-6 and (HCN)-C-13 4-3, which represent direct evidence for previously unobserved outflows. The mass contained in these outflows is a significant fraction of the cluster gas masses, which suggests we are witnessing a short but important phase. Further evidence of this is the finding of a molecular shell around the only SSC visible at near-IR wavelengths. We model the P-Cygni line profiles to constrain the outflow geometry, finding that the outflows must be nearly spherical. Through a comparison of the outflow properties with predictions from simulations, we find that none of the available mechanisms completely explains the observations, although dust-reprocessed radiation pressure and O star stellar winds are the most likely candidates. The observed outflows will have a very substantial effect on the clusters' evolution and star formation efficiency.
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| 6. |
- Lump, Edina, et al.
(författare)
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A molecular tweezer antagonizes seminal amyloids and HIV infection
- 2015
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Ingår i: eLIFE. - 2050-084X. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Semen is the main vector for HIV transmission and contains amyloid fibrils that enhance viral infection. Available microbicides that target viral components have proven largely ineffective in preventing sexual virus transmission. In this study, we establish that CLR01, a 'molecular tweezer' specific for lysine and arginine residues, inhibits the formation of infectivity-enhancing seminal amyloids and remodels preformed fibrils. Moreover, CLR01 abrogates semen-mediated enhancement of viral infection by preventing the formation of virion-amyloid complexes and by directly disrupting the membrane integrity of HIV and other enveloped viruses. We establish that CLR01 acts by binding to the target lysine and arginine residues rather than by a non-specific, colloidal mechanism. CLR01 counteracts both host factors that may be important for HIV transmission and the pathogen itself. These combined anti-amyloid and antiviral activities make CLR01 a promising topical microbicide for blocking infection by HIV and other sexually transmitted viruses.
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| 7. |
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| 8. |
- Sassi, Atfa, et al.
(författare)
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Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels
- 2014
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 133:5, s. 1410-U681
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recurrent bacterial and fungal infections, eczema, and increased serum IgE levels characterize patients with the hyper-IgE syndrome (HIES). Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. However, glycosylation defects have not been described in patients with HIES. One crucial enzyme in the glycosylation pathway is phosphoglucomutase 3 (PGM3), which catalyzes a key step in the synthesis of uridine diphosphate N-acetylglucosamine, which is required for the biosynthesis of N-glycans. Objective: We sought to elucidate the genetic cause in patients with HIES who do not carry mutations in STAT3 or DOCK8. Methods: After establishing a linkage interval by means of SNPchip genotyping and homozygosity mapping in 2 families with HIES from Tunisia, mutational analysis was performed with selector-based, high-throughput sequencing. Protein expression was analyzed by means of Western blotting, and glycosylation was profiled by using mass spectrometry. Results: Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. The mutations predict amino acid changes in PGM3 (p. Glu340del and p. Leu83Ser). A third homozygous mutation (p. Asp502Tyr) and the p. Leu83Ser variant were identified in 2 other affected families, respectively. These hypomorphic mutations have an effect on the biosynthetic reactions involving uridine diphosphate N-acetylglucosamine. Glycomic analysis revealed an aberrant glycosylation pattern in leukocytes demonstrated by a reduced level of tri-antennary and tetra-antennary N-glycans. T-cell proliferation and differentiation were impaired in patients. Most patients had developmental delay, and many had psychomotor retardation. Conclusion: Impairment of PGM3 function leads to a novel primary (inborn) error of development and immunity because biallelic hypomorphic mutations are associated with impaired glycosylation and a hyper-IgE-like phenotype.
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| 9. |
- Syvänen, Stina, et al.
(författare)
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PET Imaging in Preclinical Anti-Aβ Drug Development
- 2022
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Ingår i: Pharmaceutical research. - : Springer Nature. - 0724-8741 .- 1573-904X. ; 39:7, s. 1481-1496
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Forskningsöversikt (refereegranskat)abstract
- Positron emission tomography (PET), a medical imaging technique allowing for studies of the living human brain, has gained an important role in clinical trials of novel drugs against Alzheimer’s disease (AD). For example, PET data contributed to the conditional approval in 2021 of aducanumab, an antibody directed towards amyloid-beta (Aβ) aggregates, by showing a dose-dependent reduction in brain amyloid after treatment. In parallel to clinical studies, preclinical studies in animal models of Aβ pathology may also benefit from PET as a tool to detect target engagement and treatment effects of anti-Aβ drug candidates. PET is associated with a high level of translatability between species as similar, non-invasive protocols allow for longitudinal rather than cross-sectional studies and can be used both in a preclinical and clinical setting. This review focuses on the use of preclinical PET imaging in genetically modified animals that express human Aβ, and its present and potential future role in the development of drugs aimed at reducing brain Aβ levels as a therapeutic strategy to halt disease progression in AD.
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