2,315 research outputs found
Coastal defence by the Allied forces behind the Yser front: about arms, water, sand and patients
Recognising and Enabling the Collective Dimension of the GDPR and the Right of Access:A call to support the governance structure of checks and balances for informational power asymmetries
Getting Data Subject Rights Right:A submission to the European Data Protection Board from international data rights academics, to inform regulatory guidance
Bar coding MS2 spectra for metabolite identification
[Image: see text] Metabolite identifications are most frequently achieved in untargeted metabolomics by matching precursor mass and full, high-resolution MS(2) spectra to metabolite databases and standards. Here we considered an alternative approach for establishing metabolite identifications that does not rely on full, high-resolution MS(2) spectra. First, we select mass-to-charge regions containing the most informative metabolite fragments and designate them as bins. We then translate each metabolite fragmentation pattern into a binary code by assigning 1’s to bins containing fragments and 0’s to bins without fragments. With 20 bins, this binary-code system is capable of distinguishing 96% of the compounds in the METLIN MS(2) library. A major advantage of the approach is that it extends untargeted metabolomics to low-resolution triple quadrupole (QqQ) instruments, which are typically less expensive and more robust than other types of mass spectrometers. We demonstrate a method of acquiring MS(2) data in which the third quadrupole of a QqQ instrument cycles over 20 wide isolation windows (coinciding with the location and width of our bins) for each precursor mass selected by the first quadrupole. Operating the QqQ instrument in this mode yields diagnostic bar codes for each precursor mass that can be matched to the bar codes of metabolite standards. Furthermore, our data suggest that using low-resolution bar codes enables QqQ instruments to make MS(2)-based identifications in untargeted metabolomics with a specificity and sensitivity that is competitive to high-resolution time-of-flight technologies
Towards understanding the variability in biospheric CO2 fluxes:Using FTIR spectrometry and a chemical transport model to investigate the sources and sinks of carbonyl sulfide and its link to CO2
Understanding carbon dioxide (CO2) biospheric processes is of great importance because the terrestrial exchange drives the seasonal and interannual variability of CO2 in the atmosphere. Atmospheric inversions based on CO2 concentration measurements alone can only determine net biosphere fluxes, but not differentiate between photosynthesis (uptake) and respiration (production). Carbonyl sulfide (OCS) could provide an important additional constraint: it is also taken up by plants during photosynthesis but not emitted during respiration, and therefore is a potential means to differentiate between these processes. Solar absorption Fourier Transform InfraRed (FTIR) spectrometry allows for the retrievals of the atmospheric concentrations of both CO2 and OCS from measured solar absorption spectra. Here, we investigate co-located and quasi-simultaneous FTIR measurements of OCS and CO2 performed at five selected sites located in the Northern Hemisphere. These measurements are compared to simulations of OCS and CO2 using a chemical transport model (GEOS-Chem). The coupled biospheric fluxes of OCS and CO2 from the simple biosphere model (SiB) are used in the study. The CO2 simulation with SiB fluxes agrees with the measurements well, while the OCS simulation reproduced a weaker drawdown than FTIR measurements at selected sites, and a smaller latitudinal gradient in the Northern Hemisphere during growing season when comparing with HIPPO (HIAPER Pole-to-Pole Observations) data spanning both hemispheres. An offset in the timing of the seasonal cycle minimum between SiB simulation and measurements is also seen. Using OCS as a photosynthesis proxy can help to understand how the biospheric processes are reproduced in models and to further understand the carbon cycle in the real world
LPS resistance of SPRET/Ei mice is mediated by Gilz, encoded by the Tsc22d3 gene on the X chromosome
Natural variation for LPS-induced lethal inflammation in mice is useful for identifying new genes that regulate sepsis, which could form the basis for novel therapies for systemic inflammation in humans. Here we report that LPS resistance of the inbred mouse strain SPRET/Ei, previously reported to depend on the glucocorticoid receptor (GR), maps to the distal region of the X-chromosome. The GR-inducible gene Tsc22d3, encoding the protein Gilz and located in the critical region on the X-chromosome, showed a higher expressed SPRET/Ei allele, regulated in cis. Higher Gilz levels were causally related to reduced inflammation, as shown with knockdown and overexpression studies in macrophages. Transient overexpression of Gilz by hydrodynamic plasmid injection confirmed that Gilz protects mice against endotoxemia Our data strongly suggest that Gilz is responsible for the LPS resistance of SPRET/Ei mice and that it could become a treatment option for sepsis
VUV and X-ray coherent light with tunable polarization from single-pass free-electron lasers
Tunable polarization over a wide spectral range is a required feature of
light sources employed to investigate the properties of local symmetry in both
condensed and low-density matter. Among new-generation sources, free-electron
lasers possess a unique combination of very attractive features, as they allow
to generate powerful and coherent ultra-short optical pulses in the VUV and
X-ray spectral range. However, the question remains open about the possibility
to freely vary the light polarization of a free-electron laser, when the latter
is operated in the so-called nonlinear harmonic-generation regime. In such
configuration, one collects the harmonics of the free-electron laser
fundamental emission, gaining access to the shortest possible wavelengths the
device can generate. In this letter we provide the first experimental
characterization of the polarization of the harmonic light produced by a
free-electron laser and we demonstrate a method to obtain tunable polarization
in the VUV and X-ray spectral range. Experimental results are successfully
compared to those obtained using a theoretical model based on the paraxial
solution of Maxwell's equations. Our findings can be expected to have a deep
impact on the design and realization of experiments requiring full control of
light polarization to explore the symmetry properties of matter samples
Daily Exchange Rate Behaviour and Hedging of Currency Risk
Exchange rates typically exhibit time-varying patterns in both means and variances. The histograms of such series indicate heavy tails. In this paper we construct models which enable a decision-maker to analyze the implications of such time series patterns for currency risk management. Our approach is Bayesian where extensive use is made of Markov chain Monte Carlo methods. The effects of several model characteristics (unit roots, GARCH, stochastic volatility, heavy tailed disturbance densities) are investigated in relation to the hedging decision strategies. Consequently, we can make a distinction between statistical relevance of model specifications, and the economic consequences from a risk management point of view. The empirical results suggest that econometric modelling of heavy tails and time-varying means and variances pays off compared to a efficient markets model. The different ways to measure persistence and changing volatilities appear to strongly influence the hedging decision the investor faces.
Evidence that 2-hydroxyglutarate is not readily metabolized in colorectal carcinoma cells
BACKGROUND: Two-hydroxyglutarate (2HG) is present at low concentrations in healthy mammalian cells as both an L and D enantiomer. Both the L and D enantiomers have been implicated in regulating cellular physiology by mechanisms that are only partially characterized. In multiple human cancers, the D enantiomer accumulates due to gain-of-function mutations in the enzyme isocitrate dehydrogenase (IDH) and has been hypothesized to drive malignancy through mechanisms that remain incompletely understood. While much attention has been dedicated to identifying the route of 2HG synthesis, the metabolic fate of 2HG has not been studied in detail. Yet the metabolism of 2HG may have important mechanistic consequences influencing cell function and cancer pathogenesis, such as modulating redox potential or producing unknown products with unique modes of action. RESULTS: By applying our isotope-based metabolomic platform, we unbiasedly and comprehensively screened for products of L- and D-2HG in HCT116 colorectal carcinoma cells harboring a mutation in IDH1. After incubating HCT116 cells in uniformly (13)C-labeled 2HG for 24Â h, we used liquid chromatography/mass spectrometry to track the labeled carbons in small molecules. Strikingly, we did not identify any products of 2HG metabolism from the thousands of metabolomic features that we screened. Consistent with these results, we did not detect any significant changes in the labeling patterns of tricarboxylic acid cycle metabolites from wild type or IDH1 mutant cells cultured in (13)C-labeled glucose upon the addition of L, D, or racemic mixtures of 2HG. A more sensitive, targeted analysis revealed trace levels of isotopic enrichment (<1Â %) in some central carbon metabolites from (13)C-labeled 2HG. However, we found that cells do not deplete 2HG from the media at levels above our detection limit over a 48 h time period. CONCLUSIONS: Taken together, we conclude that 2HG carbon is not readily transformed in the HCT116 cell line. These data indicate that the phenotypic alterations induced by 2HG are not a result of its metabolic products
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