83 research outputs found
Modeling the variations of Dose Rate measured by RAD during the first MSL Martian year: 2012-2014
The Radiation Assessment Detector (RAD), on board Mars Science Laboratory's
(MSL) rover Curiosity, measures the {energy spectra} of both energetic charged
and neutral particles along with the radiation dose rate at the surface of
Mars. With these first-ever measurements on the Martian surface, RAD observed
several effects influencing the galactic cosmic ray (GCR) induced surface
radiation dose concurrently: [a] short-term diurnal variations of the Martian
atmospheric pressure caused by daily thermal tides, [b] long-term seasonal
pressure changes in the Martian atmosphere, and [c] the modulation of the
primary GCR flux by the heliospheric magnetic field, which correlates with
long-term solar activity and the rotation of the Sun. The RAD surface dose
measurements, along with the surface pressure data and the solar modulation
factor, are analysed and fitted to empirical models which quantitatively
demonstrate} how the long-term influences ([b] and [c]) are related to the
measured dose rates. {Correspondingly we can estimate dose rate and dose
equivalents under different solar modulations and different atmospheric
conditions, thus allowing empirical predictions of the Martian surface
radiation environment
The Preferred Substrates for Transglutaminase 2 in a Complex Wheat Gluten Digest Are Peptide Fragments Harboring Celiac Disease T-Cell Epitopes
BACKGROUND: Celiac disease is a T-cell mediated chronic inflammatory disorder of the gut that is induced by dietary exposure to gluten proteins. CD4+ T cells of the intestinal lesion recognize gluten peptides in the context of HLA-DQ2.5 or HLA-DQ8 and the gluten derived peptides become better T-cell antigens after deamidation catalyzed by the enzyme transglutaminase 2 (TG2). In this study we aimed to identify the preferred peptide substrates of TG2 in a heterogeneous proteolytic digest of whole wheat gluten. METHODS: A method was established to enrich for preferred TG2 substrates in a complex gluten peptide mixture by tagging with 5-biotinamido-pentylamine. Tagged peptides were isolated and then identified by nano-liquid chromatography online-coupled to tandem mass spectrometry, database searching and final manual data validation. RESULTS: We identified 31 different peptides as preferred substrates of TG2. Strikingly, the majority of these peptides were harboring known gluten T-cell epitopes. Five TG2 peptide substrates that were predicted to bind to HLA-DQ2.5 did not contain previously characterized sequences of T-cell epitopes. Two of these peptides elicited T-cell responses when tested for recognition by intestinal T-cell lines of celiac disease patients, and thus they contain novel candidate T-cell epitopes. We also found that the intact 9mer core sequences of the respective epitopes were not present in all peptide substrates. Interestingly, those epitopes that were represented by intact forms were frequently recognized by T cells in celiac disease patients, whereas those that were present in truncated versions were infrequently recognized. CONCLUSION: TG2 as well as gastrointestinal proteolysis play important roles in the selection of gluten T-cell epitopes in celiac disease
Zurich Consensus: German Expert Opinion on the St. Gallen Votes on 15 March 2009 (11th International Conference at St. Gallen: Primary Therapy of Early Breast Cancer)
A German working group of 23 breast cancer experts discussed the results from the vote at this year's St. Gallen Consensus Conference on Primary Therapy for Early Breast Cancer ( March 11-14, 2009) and came up with some concrete recommendations for day-to-day therapeutic decisions in Germany. Due the fact that the concept of the St. Gallen Consensus Conference merely allows for a minimal consensus, the objective of the working group was to provide practice-related recommendations for day-to-day clinical decisions in Germany. One area of emphasis at St. Gallen was tumor biology as a starting point for reaching individual therapeutic decisions. Intensive discussion was necessary with respect to the clinical relevance of predictive and prognostic factors. A new addition to the area of systemic therapy was a first-ever discussion of the adjuvant administration of bisphosponates and the fact that therapy with trastuzumab in HER2 overexpressing breast cancer has been defined as the standard for neoadjuvant therapy. The value of taxanes as a component of (neo) adjuvant chemotherapy as well as the value of aromatase inhibitors for the endocrine adjuvant treatment of postmenopausal patients were affirmed
The VADA Architecture for Cost-Effective Data Wrangling
Data wrangling, the multi-faceted process by which the data
required by an application is identified, extracted, cleaned
and integrated, is often cumbersome and labor intensive.
In this paper, we present an architecture that supports a
complete data wrangling lifecycle, orchestrates components
dynamically, builds on automation wherever possible, is informed
by whatever data is available, refines automatically
produced results in the light of feedback, takes into account
the user’s priorities, and supports data scientists with diverse
skill sets. The architecture is demonstrated in practice
for wrangling property sales and open government data
No Effect of Microgravity and Simulated Mars Gravity on Final Bacterial Cell Concentrations on the International Space Station: Applications to Space Bioproduction
Microorganisms perform countless tasks on Earth and they are expected to be essential
for human space exploration. Despite the interest in the responses of bacteria to space
conditions, the findings on the effects of microgravity have been contradictory, while
the effects of Martian gravity are nearly unknown. We performed the ESA BioRock
experiment on the International Space Station to study microbe-mineral interactions in
microgravity, simulated Mars gravity and simulated Earth gravity, as well as in ground
gravity controls, with three bacterial species: Sphingomonas desiccabilis, Bacillus
subtilis, and Cupriavidus metallidurans. To our knowledge, this was the first experiment
to study simulated Martian gravity on bacteria using a space platform. Here, we tested
the hypothesis that different gravity regimens can influence the final cell concentrations
achieved after a multi-week period in space. Despite the different sedimentation rates
predicted, we found no significant differences in final cell counts and optical densities
between the three gravity regimens on the ISS. This suggests that possible gravityrelated effects on bacterial growth were overcome by the end of the experiment. The
results indicate that microbial-supported bioproduction and life support systems can be
effectively performed in space (e.g., Mars), as on Earth
The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors
The Science Performance of JWST as Characterized in Commissioning
This paper characterizes the actual science performance of the James Webb
Space Telescope (JWST), as determined from the six month commissioning period.
We summarize the performance of the spacecraft, telescope, science instruments,
and ground system, with an emphasis on differences from pre-launch
expectations. Commissioning has made clear that JWST is fully capable of
achieving the discoveries for which it was built. Moreover, almost across the
board, the science performance of JWST is better than expected; in most cases,
JWST will go deeper faster than expected. The telescope and instrument suite
have demonstrated the sensitivity, stability, image quality, and spectral range
that are necessary to transform our understanding of the cosmos through
observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures;
https://iopscience.iop.org/article/10.1088/1538-3873/acb29
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