Bayesian Deconvolution and Quantification of Metabolites from J-Resolved NMR Spectroscopy

Two-dimensional (2D) nuclear magnetic resonance (nmr) methods have become increasingly popular in metabolomics, since they have considerable potential to accurately identify and quantify metabolites within complex biological samples. 2D 1 H J-resolved (jres) nmr spectroscopy is a widely used method that expands overlapping resonances into a second dimension. However, existing analytical processing methods do not fully exploit the information in the jres spectrum and, more importantly, do not provide measures of uncertainty associated with the estimates of quantities of interest, such as metabolite concentration. Combining the data-generating mechanisms and the extensive prior knowledge available in online databases, we develop a Bayesian method to analyse 2D jres data, which allows for automatic deconvolution, identification and quantification of metabolites. The model extends and improves previous work on one-dimensional nmr spectral data. Our approach is based on a combination of B-spline tight wavelet frames and theoretical templates, and thus enables the automatic incorporation of expert knowledge within the inferential framework. Posterior inference is performed through specially devised Markov chain Monte Carlo methods. We demonstrate the performance of our approach via analyses of datasets from serum and urine, showing the advantages of our proposed approach in terms of identification and quantification of metabolites

The need to transform Science Communication from being multi-cultural via cross-cultural to intercultural

When dealing with issues that are of high societal relevance, Earth sciences still face a lack of acceptance, which is partly rooted in insufficient communication strategies on the individual and local community level. To increase the efficiency of communication routines, science has to transform its outreach concepts to become more aware of individual needs and demands. The “encoding/decoding” concept as well as critical intercultural communication studies can offer pivotal approaches for this transformation.</p

Upper critical field pecularities of superconducting YNi2B2C and LuNi2B2C

We present new upper critical field Hc2(T) data in a broad temperature region from 0.3K to Tc for LuNi2B2C and YNi2B2C single crystals with well characterized low impurity scattering rates. The absolute values for all T, in particular Hc2(0), and the sizeable positive curvature (PC) of Hc2(T) at high and intermediate T are explained quantitatively within an effective two-band model. The failure of the isotropic single band approach is discussed in detail. Supported by de Haas van Alphen data, the superconductivity reveals direct insight into details of the electronic structure. The observed maximal PC near Tc gives strong evidence for clean limit type II superconductors.Comment: 4 pages, 2 figures, Phys. Rev. Lett. accepte

Hydroclimate in the Pamirs Was Driven by Changes in Precipitation‐Evaporation Seasonality Since theLast Glacial Period

The Central Asian Pamir Mountains (Pamirs) are a high‐altitude region sensitive to climatic change, with only few paleoclimatic records available. To examine the glacial‐interglacial hydrological changes in the region, we analyzed the geochemical parameters of a 31‐kyr record from Lake Karakul and performed a set of experiments with climate models to interpret the results. δD values of terrestrial biomarkers showed insolation‐driven trends reflecting major shifts of water vapor sources. For aquatic biomarkers, positive δD shifts driven by changes in precipitation seasonality were observed at ca. 31–30, 28–26, and 17–14 kyr BP. Multiproxy paleoecological data and modelling results suggest that increased water availability, induced by decreased summer evaporation, triggered higher lake levels during those episodes, possibly synchronous to northern hemispheric rapid climate events. We conclude that seasonal changes in precipitation‐evaporation balance significantly influenced the hydrological state of a large waterbody such as Lake Karakul, while annual precipitation amount and inflows remained fairly constant

Bcl-xL Deamidation Is a Critical Switch in the Regulation of the Response to DNA Damage

AbstractThe therapeutic value of DNA-damaging antineoplastic agents is dependent upon their ability to induce tumor cell apoptosis while sparing most normal tissues. Here, we show that a component of the apoptotic response to these agents in several different types of tumor cells is the deamidation of two asparagines in the unstructured loop of Bcl-xL, and we demonstrate that deamidation of these asparagines imports susceptibility to apoptosis by disrupting the ability of Bcl-xL to block the proapoptotic activity of BH3 domain-only proteins. Conversely, Bcl-xL deamidation is actively suppressed in fibroblasts, and suppression of deamidation is an essential component of their resistance to DNA damage-induced apoptosis. Our results suggest that the regulation of Bcl-xL deamidation has a critical role in the tumor-specific activity of DNA-damaging antineoplastic agents

Serum Bilirubin and Ferritin Levels Link Heme Oxygenase-1 Gene Promoter Polymorphism and Susceptibility to Coronary Artery Disease in Diabetic Patients

OBJECTIVE—Heme oxygenase (HO) leads to the generation of free iron, carbon monoxide, and bilirubin. A length polymorphism of GT repeats in the promoter of human HO-1 gene has been shown to modulate gene transcription. The aim of this study was to assess the association of the length of (GT)n repeats in the HO-1 gene promoter with serum bilirubin, markers of iron status, and the development of coronary artery disease (CAD)

Neutrophil Extracellular Trap–Derived Enzymes Oxidize High‐Density Lipoprotein: An Additional Proatherogenic Mechanism in Systemic Lupus Erythematosus

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108351/1/art38703.pd