We present the first detailed elemental abundances in the ultra-faint Magellanic satellite galaxies Carina II (Car II) and Carina III (Car III). With high-resolution Magellan/MIKE spectroscopy, we ...determined the abundances of nine stars in Car II, including the first abundances of an RR Lyrae star in an ultra-faint dwarf galaxy (UFD), and two stars in Car III. The chemical abundances demonstrate that both systems are clearly galaxies and not globular clusters. The stars in these galaxies mostly display abundance trends matching those of other similarly faint dwarf galaxies: enhanced but declining /Fe ratios, iron-peak elements matching the stellar halo, and unusually low neutron-capture element abundances. One star displays a low outlying Sc/Fe = −1.0. We detect a large Ba scatter in Car II, likely due to inhomogeneous enrichment by low-mass asymptotic giant branch star winds. The most striking abundance trend is for Mg/Ca in Car II, which decreases from +0.4 to −0.4 and indicates clear variation in the initial progenitor masses of enriching core-collapse supernovae. So far, the only UFDs displaying a similar Mg/Ca trend are likely satellites of the Large Magellanic Cloud. We find two stars with Fe/H ≤ −3.5 whose abundances likely trace the first generation of metal-free Population III stars and are well fit by Population III core-collapse supernova yields. An appendix describes our new abundance uncertainty analysis that propagates line-by-line stellar parameter uncertainties.
To extend the coverage of brain coil arrays to the neck and cervical-spine region to enable combined head and neck imaging at 7 Tesla (T) ultra-high field MRI.
The coil array structures of a ...64-channel receive coil and a 16-channel transmit coil were merged into one anatomically shaped close-fitting housing. Transmit characteristics were evaluated in a B
-field mapping study and an electromagnetic model. Receive SNR and the encoding capability for accelerated imaging were evaluated and compared with a commercially available 7 T brain array coil. The performance of the head-neck array coil was demonstrated in human volunteers using high-resolution accelerated imaging.
In the brain, the SNR matches the commercially available 32-channel brain array and showed improvements in accelerated imaging capabilities. More importantly, the constructed coil array improved the SNR in the face area, neck area, and cervical spine by a factor of 1.5, 3.4, and 5.2, respectively, in regions not covered by 32-channel brain arrays at 7 T. The interelement coupling of the 16-channel transmit coil ranged from -14 to -44 dB (mean = -19 dB, adjacent elements <-18 dB). The parallel 16-channel transmit coil greatly facilitates B
field shaping required for large FOV neuroimaging at 7 T.
This new head-neck array coil is the first demonstration of a device of this nature used for combined full-brain, head-neck, and cervical-spine imaging at 7 T. The array coil is well suited to provide large FOV images, which potentially improves ultrahigh field neuroimaging applications for clinical settings.
A set of model nucleophiles of gradually changing nucleophilicity is used to probe the glycosylation reaction mechanism. Glycosylations of ethanol-based acceptors, bearing varying amounts of fluorine ...atoms, report on the dependency of the stereochemistry in condensation reactions on the nucleophilicity of the acceptor. Three different glycosylation systems were scrutinized, that differ in the reaction mechanism, that - putatively - prevails during the coupling reaction. It is revealed that the stereoselectivity in glycosylations of benzylidene protected glucose donors are very susceptible to acceptor nucleophilicity whereas condensations of benzylidene mannose and mannuronic acid donors represent more robust glycosylation systems in terms of diastereoselectivity. The change in stereoselectivity with decreasing acceptor nucleophilicity is related to a change in reaction mechanism shifting from the S
2 side to the S
1 side of the reactivity spectrum. Carbohydrate acceptors are examined and the reactivity-selectivity profile of these nucleophiles mirrored those of the model acceptors studied. The set of model ethanol acceptors thus provides a simple and effective "toolbox" to investigate glycosylation reaction mechanisms and report on the robustness of glycosylation protocols.
The Danish Eulerian Hemispheric Model (DEHM) is a 3D long-range atmospheric chemistry-transport model with a horizontal domain covering the Northern Hemisphere. For the AQMEII (Air Quality Modelling ...Evaluation International Initiative) inter-comparison exercise, the model was set up with two two-way nested domains simultaneously – one covering Europe and one covering North America. In this paper, the model configuration used in AQMEII will be described, including a discussion of model results and evaluation for the year 2006 against available measurements in Europe for different chemical species. The evaluation of DEHM for Europe shows that the model gives satisfying results for species such as ozone, nitrogen-dioxide, sulphur-dioxide and secondary inorganic aerosols. The evaluation also points to certain processes where DEHM can be improved, such as biogenic emissions of isoprene, mass closure for particulate matter, wet deposition, and description of vertical mixing during winter. Furthermore, special attention is given to the intercontinental transport of air pollution between North America (NA) and Europe (EU). We estimate the contributions to the total air pollution levels at continental scale from the anthropogenic emissions in the two areas, with a focus on ozone and particulate matter using a tagging method, taking into account the non-linear effects of atmospheric chemistry. We conclude that for this specific year, the intercontinental transport between NA and EU is small for the annual or seasonal mean values – for ozone the contributions are typically around 3% (∼1 ppb) from NA to EU and around 1% (∼0.3 ppb) from EU to NA. For particles the contributions from NA to EU is around 0.9% (∼0.05 μg m−3) and from EU to NA around 1.4% (∼0.05 μg m−3).
► We model the air pollution in North America and Europe for the year 2006 using DEHM. ► We evaluate the model results against measurements for Europe for all available species. ► The evaluation leads to conclusions on where to improve the model. ► We calculated the intercontinental transport of air pollution between North America and Europe. ► We found that the exchange of air pollution between the two continents is small on the annual basis.
Purpose
Three 64‐channel cardiac coils with different detector array configurations were designed and constructed to evaluate acceleration capabilities in simultaneous multislice (SMS) imaging for 3T ...cardiac MRI.
Methods
Three 64‐channel coil array configurations obtained from a simulation‐guided design approach were constructed and systematically evaluated regarding their encoding capabilities for accelerated SMS cardiac acquisitions at 3T. Array configuration AUni‐sized consists of uniformly distributed equally sized loops in an overlapped arrangement, BGapped uses a gapped array design with symmetrically distributed equally sized loops, and CDense has non‐uniform loop density and size, where smaller elements were centered over the heart and larger elements were placed surrounding the target region. To isolate the anatomic variation from differences in the coil configurations, all three array coils were built with identical semi‐adjustable housing segments. The arrays’ performance was compared using bench‐level measurements and imaging performance tests, including signal‐to‐noise ratio (SNR) maps, array element noise correlation, and SMS acceleration capabilities. Additionally, all cardiac array coils were evaluated on a healthy volunteer.
Results
The array configuration CDense with the non‐uniformly distributed loop density showed the best overall cardiac imaging performance in both SNR and SMS encoding power, when compared to the other constructed arrays. The diffusion weighted cardiac acquisitions on a healthy volunteer support the favorable accelerated SNR performance of this array configuration.
Conclusion
Our results indicate that optimized highly parallel cardiac arrays, such as the 64‐channel coil with a non‐uniform loop size and density improve highly accelerated SMS cardiac MRI in comparison to symmetrically distributed loop array designs.
Summary
Background
Pachyonychia congenita (PC) is a rare autosomal dominant keratinizing disorder characterized by severe, painful, palmoplantar keratoderma and nail dystrophy, often accompanied by ...oral leucokeratosis, cysts and follicular keratosis. It is caused by mutations in one of five keratin genes: KRT6A, KRT6B, KRT6C, KRT16 or KRT17.
Objectives
To identify mutations in 84 new families with a clinical diagnosis of PC, recruited by the International Pachyonychia Congenita Research Registry during the last few years.
Methods
Genomic DNA isolated from saliva or peripheral blood leucocytes was amplified using primers specific for the PC‐associated keratin genes and polymerase chain reaction products were directly sequenced.
Results
Mutations were identified in 84 families in the PC‐associated keratin genes, comprising 46 distinct keratin mutations. Fourteen were previously unreported mutations, bringing the total number of different keratin mutations associated with PC to 105.
Conclusions
By identifying mutations in KRT6A, KRT6B, KRT6C, KRT16 or KRT17, this study has confirmed, at the molecular level, the clinical diagnosis of PC in these families.
What's already known about this topic?
Pachyonychia congenita (PC) is caused by autosomal dominant mutations in KRT6A, KRT6B, KRT6C, KRT16 or KRT17.
Plantar pain is the main symptom.
Palmoplantar keratoderma and nail dystrophy are the predominant characteristics, often accompanied by oral leucokeratosis, cysts and follicular keratosis.
What does this study add?
This study identifies PC‐associated keratin mutations in 84 new families with PC recruited by the International Pachyonychia Congenita Research Registry.
Fourteen of the 46 distinct keratin mutations were previously unreported.
This study expands the large well‐phenotyped and genotyped case series of patients with PC, which is an invaluable resource for the development of mutation‐specific and/or gene‐specific therapies and for future clinical trials.
De novo genetic variation is an important class of risk factors for autism spectrum disorder (ASD). Recently, whole-exome sequencing of ASD families has identified a novel de novo missense mutation ...in the human dopamine (DA) transporter (hDAT) gene, which results in a Thr to Met substitution at site 356 (hDAT T356M). The dopamine transporter (DAT) is a presynaptic membrane protein that regulates dopaminergic tone in the central nervous system by mediating the high-affinity reuptake of synaptically released DA, making it a crucial regulator of DA homeostasis. Here, we report the first functional, structural and behavioral characterization of an ASD-associated de novo mutation in the hDAT. We demonstrate that the hDAT T356M displays anomalous function, characterized as a persistent reverse transport of DA (substrate efflux). Importantly, in the bacterial homolog leucine transporter, substitution of A289 (the homologous site to T356) with a Met promotes an outward-facing conformation upon substrate binding. In the substrate-bound state, an outward-facing transporter conformation is required for substrate efflux. In Drosophila melanogaster, the expression of hDAT T356M in DA neurons-lacking Drosophila DAT leads to hyperlocomotion, a trait associated with DA dysfunction and ASD. Taken together, our findings demonstrate that alterations in DA homeostasis, mediated by aberrant DAT function, may confer risk for ASD and related neuropsychiatric conditions.
Outer planet auroras have been imaged for more than a decade, yet understanding their physical origin requires simultaneous remote and in situ observations. The first such measurements at Saturn were ...obtained in January 2007, when the Hubble Space Telescope imaged the ultraviolet aurora, while the Cassini spacecraft crossed field lines connected to the auroral oval in the high‐latitude magnetosphere near noon. The Cassini data indicate that the noon aurora lies in the boundary between open‐ and closed‐field lines, where a layer of upward‐directed field‐aligned current flows whose density requires downward acceleration of magnetospheric electrons sufficient to produce the aurora. These observations indicate that the quasi‐continuous main oval is produced by the magnetosphere‐solar wind interaction through the shear in rotational flow across the open‐closed‐field line boundary.
Interferons induced early after SARS-CoV-2 infection are crucial for shaping immunity and preventing severe COVID-19. We previously demonstrated that injection of pegylated interferon-lambda ...accelerated viral clearance in COVID-19 patients (NCT04354259). To determine if the viral decline is mediated by enhanced immunity, we assess in vivo responses to interferon-lambda by single cell RNA sequencing and measure SARS-CoV-2-specific T cell and antibody responses between placebo and interferon-lambda-treated patients. Here we show that interferon-lambda treatment induces interferon stimulated genes in peripheral immune cells expressing IFNLR1, including plasmacytoid dendritic cells and B cells. Interferon-lambda does not affect SARS-CoV-2-specific antibody levels or the magnitude of virus-specific T cells. However, we identify delayed T cell responses in older adults, suggesting that interferon-lambda can overcome delays in adaptive immunity to accelerate viral clearance in high-risk patients. Altogether, interferon-lambda offers an early COVID-19 treatment option for outpatients to boost innate antiviral defenses without dampening peripheral adaptive immunity.
PDF
