690 research outputs found
Hidden deep in the halo: Selection of a reduced proper motion halo catalogue and mining retrograde streams in the velocity space
The Milky Way halo is one of the few galactic haloes that provides a unique
insight into galaxy formation by resolved stellar populations. Here, we present
a catalogue of 47 million halo stars selected independent of parallax and
line-of-sight velocities, using a combination of Gaia DR3 proper motion and
photometry by means of their reduced proper motion. We select high tangential
velocity (halo) main sequence stars and fit distances to them using their
simple colour-absolute-magnitude relation. This sample reaches out to 21
kpc with a median distance of kpc thereby probing much further out than
would be possible using reliable Gaia parallaxes. The typical uncertainty in
their distances is kpc. Using the colour range
where the main sequence is narrower, gives
an even better accuracy down to kpc in distance. The
median velocity uncertainty for stars within this colour range is 15.5 km/s.
The distribution of these sources in the sky, together with their tangential
component velocities, are very well-suited to study retrograde substructures.
We explore the selection of two complex retrograde streams: GD-1 and Jhelum.
For these streams, we resolve the gaps, wiggles and density breaks reported in
the literature more clearly. We also illustrate the effect of the kinematic
selection bias towards high proper motion stars and incompleteness at larger
distances due to Gaia's scanning law. These examples showcase how the full RPM
catalogue made available here can help us paint a more detailed picture of the
build-up of the Milky Way halo.Comment: 17 pages. Accepted for publication in MNRAS. The catalogue has been
submitted as supplementary material to CDS and MNRAS for use to do more
wonderful science. Comments are welcomed and appreciated
Peanut allergen Ara h 6 is detectable in blood transfusion products
Peanut allergen Ara h 6 is known to maintain IgE‐binding capacity upon exposure to digestive enzymes1 and its presence in circulation after consumption of peanut has been demonstrated.2,3 Therefore, it has been speculated that food‐derived allergens could be transferred via blood transfusion products, causing an allergic reaction in food-allergic recipients.4,5 However, in published case reports, presence of food allergen in donated material could not be confirmed due to lack of remaining transfusion material and/or lack of sensitive analytical methods. Using a newly developed sensitive immune‐assay for detecting Ara h 6 in human serum, we now report to what extent consumed peanut allergens can be present in blood transfusion materials and estimate the associated risk for peanut‐allergic recipients
Association of Interacting Genes in the Toll-Like Receptor Signaling Pathway and the Antibody Response to Pertussis Vaccination
BACKGROUND: Activation of the Toll-like receptor (TLR) signaling pathway through TLR4 may be important in the induction of protective immunity against Bordetella pertussis with TLR4-mediated activation of dendritic and B cells, induction of cytokine expression, and reversal of tolerance as crucial steps. We examined whether single nucleotide polymorphisms (SNPs) in genes of the TLR4 pathway and their interaction are associated with the response to whole-cell vaccine (WCV) pertussis vaccination in 490 one-year-old children. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed associations of 75 haplotype-tagging SNPs in genes in the TLR4 signaling pathway with pertussis toxin (PT)-IgG titers. We found significant associations between the PT-IgG titer and SNPs in CD14, TLR4, TOLLIP, TIRAP, IRAK3, IRAK4, TICAM1, and TNFRSF4 in one or more of the analyses. The strongest evidence for association was found for two SNPs (rs5744034 and rs5743894) in TOLLIP that were almost completely in linkage disequilibrium, provided statistically significant associations in all tests with the lowest p-values, and displayed a dominant mode of inheritance. However, none of these single gene associations would withstand correction for multiple testing. In addition, Multifactor Dimensionality Reduction Analysis, an approach that does not need correction for multiple testing, showed significant and strong two and three locus interactions between SNPs in TOLLIP (rs4963060), TLR4 (rs6478317) and IRAK1 (rs1059703). CONCLUSIONS/SIGNIFICANCE: We have identified significant interactions between genes in the TLR pathway in the induction of vaccine-induced immunity. These interactions underline that these genes are functionally related and together form a true biological relationship in a protein-protein interaction network. Practically all our findings may be explained by genetic variation in directly or indirectly interacting proteins at the extra- and intracytoplasmic sites of the cell membrane of antigen-presenting cells, B cells, or both. Fine tuning of interacting proteins in the TLR pathway appears important for the induction of an optimal vaccine response
Practical solutions for sampling alternatives in large-scale models
Many large-scale real-world transport applications have choice sets that are so large as to make model estimation and application computationally impractical. The ability to estimate models on subsets of the alternatives is thus of great appeal, and correction approaches have existed since the late 1970s for the simple multinomial logit (MNL) model. However, many of these models in practice rely on nested logit specifications, for example, in the context of the joint choice of mode and destination. Recent research has put forward solutions for such generalized extreme value (GEV) structures, but these structures remain difficult to apply in practice. This paper puts forward a simplification of the GEV method for use in computationally efficient implementations of nested logit. The good performance of this approach is illustrated with simulated data, and additional insights into sampling error are also provided with different sampling strategies for MNL
A Massive Data Parallel Computational Framework for Petascale/Exascale Hybrid Computer Systems
large scale scientific applicatio
The merger that led to the formation of the Milky Way's inner stellar halo and thick disk
The assembly process of our Galaxy can be retrieved using the motions and
chemistry of individual stars. Chemo-dynamical studies of the nearby halo have
long hinted at the presence of multiple components such as streams, clumps,
duality and correlations between the stars' chemical abundances and orbital
parameters. More recently, the analysis of two large stellar surveys have
revealed the presence of a well-populated chemical elemental abundance
sequence, of two distinct sequences in the colour-magnitude diagram, and of a
prominent slightly retrograde kinematic structure all in the nearby halo, which
may trace an important accretion event experienced by the Galaxy. Here report
an analysis of the kinematics, chemistry, age and spatial distribution of stars
in a relatively large volume around the Sun that are mainly linked to two major
Galactic components, the thick disk and the stellar halo. We demonstrate that
the inner halo is dominated by debris from an object which at infall was
slightly more massive than the Small Magellanic Cloud, and which we refer to as
Gaia-Enceladus. The stars originating in Gaia-Enceladus cover nearly the full
sky, their motions reveal the presence of streams and slightly retrograde and
elongated trajectories. Hundreds of RR Lyrae stars and thirteen globular
clusters following a consistent age-metallicity relation can be associated to
Gaia-Enceladus on the basis of their orbits. With an estimated 4:1 mass-ratio,
the merger with Gaia-Enceladus must have led to the dynamical heating of the
precursor of the Galactic thick disk and therefore contributed to the formation
of this component approximately 10 Gyr ago. These findings are in line with
simulations of galaxy formation, which predict that the inner stellar halo
should be dominated by debris from just a few massive progenitors.Comment: 19 pages, 8 figures. Published in Nature in the issue of Nov. 1st,
2018. This is the authors' version before final edit
Clinical relevance of sensitization to lupine in peanut-sensitized adults
Background: The use of lupine in food has been increasing during the last decade and allergic reactions to lupine have been reported, especially in peanut-allergic patients. The frequency and the degree of cross-reactivity to other legumes are not known. The aim of the study was to investigate the frequency of sensitization to lupine, and in addition to pea and soy, and its clinical relevance, in peanutsensitized patients. Furthermore, to determine the eliciting dose (ED) for lupine using double-blind placebo-controlled food challenges (DBPCFC).
Methods: Thirty-nine unselected peanut-sensitized patients were evaluated by skin prick tests (SPT) and ImmunoCAP to lupine, pea, and soy. Clinical reactivity was measured by DBPCFC for lupine, and by history for pea and soy.
Results: Eighty-two percent of the study population was sensitized to lupine, 55% to pea, and 87% to soy. Clinically relevant sensitization to lupine, pea, or soy occurred in 35%, 29%, and 33% respectively of the study population. None of the patients was aware of the use of lupine in food. The lowest ED for lupine, inducing mild subjective symptoms, was 0.5 mg, and the no observed adverse effect level (NOAEL) was 0.1 mg. No predictive factors for lupine allergy were found.
Conclusion: In peanut-sensitized patients, clinically relevant sensitization to either lupine or to pea or soy occurs frequently. The ED for lupine is low (0.5 mg), which is only five fold higher than for peanut. Patients are not aware of lupine allergy and the presence of lupine in food, indicating that education is important to build awareness
Colistin dry powder inhalation with the Twincer (TM):An effective and more patient friendly alternative to nebulization
BACKGROUND: Nebulization of antimicrobial drugs such as tobramycin and colistin is a cornerstone in the treatment of patients with cystic fibrosis (CF) infected with Pseudomonas aeruginosa. However, nebulization has a high treatment burden. The Twincer™ is a dry powder inhaler specifically developed for the inhalation of antibiotics such as colistin. The aim of this study was to compare patient outcomes and experience with colistin dry powder by the Twincer with nebulization of colistin or tobramycin in adult CF patients in a real-life setting. METHODS: This was a retrospective study from 01-01-2015 until 01-07-2018. Effectiveness was evaluated by comparing FEV1 decline and exacerbation rate during a mean of 4.1 years of nebulization therapy prior to the initiation of the Twincer against the same values during a mean of 1.7 years of treatment with the Twincer. RESULTS: Twenty-one patients were evaluated, of whom twelve could be included in the effectiveness analysis, with a total of twenty patient years. Of all patients 71.4% preferred therapy with the Twincer over nebulization. Twincer use resulted in high treatment adherence with an average adherence rate of 92.5%. There was no significant difference in annual decline in FEV1%pred prior to and after start changing from nebulization to the use of the Twincer powder inhaler (median decline -1.56 [-5.57-5.31] and 1.35 [-8.45-6.36]) respectively, p = 0.45 (linear mixed effect model)). No significant difference was found in the number of intravenous or combined total intravenous and oral antibiotic courses during Twincer therapy compared to when using nebulization (1.68 and 2.49 courses during Twincer therapy versus 1.51 and 2.94 courses during nebulization, p = 0.88 and p = 0.63). CONCLUSION: Colistin dry powder inhalation with the Twincer is a more patient friendly alternative to nebulization, and we did not observe significant differences in the clinical outcome, regarding lung function and exacerbation rates
Functional Restoration of CFTR Nonsense Mutations in Intestinal Organoids
Background: Pharmacotherapies for people with cystic fibrosis (pwCF) who have premature termination codons (PTCs) in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are under development. Thus far, clinical studies focused on compounds that induce translational readthrough (RT) at the mRNA PTC location. Recent studies using primary airway cells showed that PTC functional restoration can be achieved through combining compounds with multiple mode-of-actions. Here, we assessed induction of CFTR function in PTC-containing intestinal organoids using compounds targeting RT, nonsense mRNA mediated decay (NMD) and CFTR protein modulation. Methods: Rescue of PTC CFTR protein was assessed by forskolin-induced swelling of 12 intestinal organoid cultures carrying distinct PTC mutations. Effects of compounds on mRNA CFTR level was assessed by RT-qPCRs. Results: Whilst response varied between donors, significant rescue of CFTR function was achieved for most donors with the quintuple combination of a commercially available pharmacological equivalent of the RT compound (ELX-02-disulfate or ELX-02ds), NMD inhibitor SMG1i, correctors VX-445 and VX-661 and potentiator VX-770. The quintuple combination of pharmacotherapies reached swelling quantities higher than the mean swelling of three VX-809/VX-770-rescued F508del/F508del organoid cultures, indicating level of rescue is of clinical relevance as VX-770/VX-809-mediated F508del/F508del rescue in organoids correlate with substantial improvement of clinical outcome. Conclusions: Whilst variation in efficacy was observed between genotypes as well as within genotypes, the data suggests that strong pharmacological rescue of PTC requires a combination of drugs that target RT, NMD and protein function
Target Exploration for Disconnected Feasible Regions in Enterprise-Driven Multilevel Product Design
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77105/1/AIAA-13908-831.pd
- …