High-Resolution Hydrogen-Deuterium Protection Factors from Sparse Mass Spectrometry Data Validated by Nuclear Magnetic Resonance Measurements

Experimental measurement of time-dependent spontaneous exchange of amide protons with deuterium of the solvent provides information on the structure and dynamical structural variation in proteins. Two experimental techniques are used to probe the exchange: NMR, which relies on different magnetic properties of hydrogen and deuterium, and MS, which exploits the change in mass due to deuteration. NMR provides residue-specific information, that is, the rate of exchange or, analogously, the protection factor (i.e., the unitless ratio between the rate of exchange for a completely unstructured state and the observed rate). MS provides information that is specific to peptides obtained by proteolytic digestion. The spatial resolution of HDX-MS measurements depends on the proteolytic pattern of the protein, the fragmentation method used, and the overlap between peptides. Different computational approaches have been proposed to extract residue-specific information from peptide-level HDX-MS measurements. Here, we demonstrate the advantages of a method recently proposed that exploits self-consistency and classifies the possible sets of protection factors into a finite number of alternative solutions compatible with experimental data. The degeneracy of the solutions can be reduced (or completely removed) by exploiting the additional information encoded in the shape of the isotopic envelopes. We show how sparse and noisy MS data can provide high-resolution protection factors that correlate with NMR measurements probing the same protein under the same conditions

Estimating Constraints for Protection Factors from HDX-MS Data

Hydrogen/deuterium exchange monitored by mass spectrometry is a promising technique for rapidly fingerprinting structural and dynamical properties of proteins. The time-dependent change in the mass of any fragment of the polypeptide chain depends uniquely on the rate of exchange of its amide hydrogens, but determining the latter from the former is generally not possible. Here, we show that, if time-resolved measurements are available for a number of overlapping peptides that cover the whole sequence, rate constants for each amide hydrogen exchange (or equivalently, their protection factors) may be extracted and the uniqueness of the solutions obtained depending on the degree of peptide overlap. However, in most cases, the solution is not unique, and multiple alternatives must be considered. We provide a statistical method that clusters the solutions to further reduce their number. Such analysis always provides meaningful constraints on protection factors and can be used in situations in which obtaining more refined experimental data is impractical. It also provides a systematic way to improve data collection strategies to obtain unambiguous information at single-residue level (e.g., for assessing protein structure predictions at atomistic level)

Subjective Mortality Hazard Shocks and the Adjustment of Consumption Expenditures

30 Halama

Farseer-NMR: automatic treatment, analysis and plotting of large, multi-variable NMR data

We present Farseer-NMR (https://git.io/vAueU), a software package to treat, evaluate and combine NMR spectroscopic data from sets of protein-derived peaklists covering a range of experimental conditions. The combined advances in NMR and molecular biology enable the study of complex biomolecular systems such as flexible proteins or large multibody complexes, which display a strong and functionally relevant response to their environmental conditions, e.g. the presence of ligands, site-directed mutations, post translational modifications, molecular crowders or the chemical composition of the solution. These advances have created a growing need to analyse those systems’ responses to multiple variables. The combined analysis of NMR peaklists from large and multivariable datasets has become a new bottleneck in the NMR analysis pipeline, whereby information-rich NMR-derived parameters have to be manually generated, which can be tedious, repetitive and prone to human error, or even unfeasible for very large datasets. There is a persistent gap in the development and distribution of software focused on peaklist treatment, analysis and representation, and specifically able to handle large multivariable datasets, which are becoming more commonplace. In this regard, Farseer-NMR aims to close this longstanding gap in the automated NMR user pipeline and, altogether, reduce the time burden of analysis of large sets of peaklists from days/weeks to seconds/minutes. We have implemented some of the most common, as well as new, routines for calculation of NMR parameters and several publication-quality plotting templates to improve NMR data representation. Farseer-NMR has been written entirely in Python and its modular code base enables facile extension

Adaptation of a Smoking Cessation and Prevention Website for Urban American Indian/Alaska Native Youth

Tobacco use among American Indian youth is a disproportionately significant problem. We adapted and modified an existing web-based and youth-focused tobacco control program to make it appropriate for young urban American Indian/Alaska Natives (AI/ANs). The results of the focus group indicate that AI/AN youth were very receptive to the use of a web-based Zine-style intervention tool. They wanted the look and feel of the website to be more oriented toward their cultural images. Future research should examine if successful programs for reducing non-ceremonial tobacco use among urban AI/AN youth can keep young irregular smokers from becoming adult smokers

The Bipolar X-Ray Jet of the Classical T Tauri Star DG Tau

This is the author accepted manuscript. The final version is available from the Astronomical Society of the Pacific via the link in this record16th Cambridge Workshop on Cool Stars, Stellar Systems and the Sun, 28 August-3 September 2010, Seattle, USAWe report on new X-ray observations of the classical T Tauri star DG Tau. DG Tau drives a collimated bi-polar jet known to be a source of X-ray emission perhaps driven by internal shocks. The rather modest extinction permits study of the jet system to distances very close to the star itself. Our initial results presented here show that the spatially resolved X-ray jet has been moving and fading during the past six years. In contrast, a stationary, very soft source much closer (≈ 0.15 − 0.2 ′′) to the star but apparently also related to the jet has brightened during the same period. We report accurate temperatures and absorption column densities toward this source, which is probably associated with the jet base or the jet collimation region.Swiss National Science Foundatio

X-Ray Spectroscopy of Stars

(abridged) Non-degenerate stars of essentially all spectral classes are soft X-ray sources. Low-mass stars on the cooler part of the main sequence and their pre-main sequence predecessors define the dominant stellar population in the galaxy by number. Their X-ray spectra are reminiscent, in the broadest sense, of X-ray spectra from the solar corona. X-ray emission from cool stars is indeed ascribed to magnetically trapped hot gas analogous to the solar coronal plasma. Coronal structure, its thermal stratification and geometric extent can be interpreted based on various spectral diagnostics. New features have been identified in pre-main sequence stars; some of these may be related to accretion shocks on the stellar surface, fluorescence on circumstellar disks due to X-ray irradiation, or shock heating in stellar outflows. Massive, hot stars clearly dominate the interaction with the galactic interstellar medium: they are the main sources of ionizing radiation, mechanical energy and chemical enrichment in galaxies. High-energy emission permits to probe some of the most important processes at work in these stars, and put constraints on their most peculiar feature: the stellar wind. Here, we review recent advances in our understanding of cool and hot stars through the study of X-ray spectra, in particular high-resolution spectra now available from XMM-Newton and Chandra. We address issues related to coronal structure, flares, the composition of coronal plasma, X-ray production in accretion streams and outflows, X-rays from single OB-type stars, massive binaries, magnetic hot objects and evolved WR stars.Comment: accepted for Astron. Astrophys. Rev., 98 journal pages, 30 figures (partly multiple); some corrections made after proof stag

Stellar winds from Massive Stars

We review the various techniques through which wind properties of massive stars - O stars, AB supergiants, Luminous Blue Variables (LBVs), Wolf-Rayet (WR) stars and cool supergiants - are derived. The wind momentum-luminosity relation (e.g. Kudritzki et al. 1999) provides a method of predicting mass-loss rates of O stars and blue supergiants which is superior to previous parameterizations. Assuming the theoretical sqrt(Z) metallicity dependence, Magellanic Cloud O star mass-loss rates are typically matched to within a factor of two for various calibrations. Stellar winds from LBVs are typically denser and slower than equivalent B supergiants, with exceptional mass-loss rates during giant eruptions Mdot=10^-3 .. 10^-1 Mo/yr (Drissen et al. 2001). Recent mass-loss rates for Galactic WR stars indicate a downward revision of 2-4 relative to previous calibrations due to clumping (e.g. Schmutz 1997), although evidence for a metallicity dependence remains inconclusive (Crowther 2000). Mass-loss properties of luminous (> 10^5 Lo) yellow and red supergiants from alternative techniques remain highly contradictory. Recent Galactic and LMC results for RSG reveal a large scatter such that typical mass-loss rates lie in the range 10^-6 .. 10^-4 Mo/yr, with a few cases exhibiting 10^-3 Mo/yr.Comment: 16 pages, 2 figures, Review paper to appear in Proc `The influence of binaries on stellar population studies', Brussels, Aug 2000 (D. Vanbeveren ed.), Kluwe

Non-thermal emission processes in massive binaries

In this paper, I present a general discussion of several astrophysical processes likely to play a role in the production of non-thermal emission in massive stars, with emphasis on massive binaries. Even though the discussion will start in the radio domain where the non-thermal emission was first detected, the census of physical processes involved in the non-thermal emission from massive stars shows that many spectral domains are concerned, from the radio to the very high energies. First, the theoretical aspects of the non-thermal emission from early-type stars will be addressed. The main topics that will be discussed are respectively the physics of individual stellar winds and their interaction in binary systems, the acceleration of relativistic electrons, the magnetic field of massive stars, and finally the non-thermal emission processes relevant to the case of massive stars. Second, this general qualitative discussion will be followed by a more quantitative one, devoted to the most probable scenario where non-thermal radio emitters are massive binaries. I will show how several stellar, wind and orbital parameters can be combined in order to make some semi-quantitative predictions on the high-energy counterpart to the non-thermal emission detected in the radio domain. These theoretical considerations will be followed by a census of results obtained so far, and related to this topic... (see paper for full abstract)Comment: 47 pages, 5 postscript figures, accepted for publication in Astronomy and Astrophysics Review. Astronomy and Astrophysics Review, in pres

Knowledge transfer & exchange through social networks: building foundations for a community of practice within tobacco control

BACKGROUND: Health services and population health innovations advance when knowledge transfer and exchange (KTE) occurs among researchers, practitioners, policy-makers and consumers using high-quality evidence. However, few KTE models have been evaluated in practice. Communities of practice (CoP) – voluntary, self-organizing, and focused groups of individuals and organizations – may provide one option. This paper outlines an approach to lay the foundation for a CoP within the area of Web-assisted tobacco interventions (WATI). The objectives of the study were to provide a data-driven foundation to inform decisions about organizing a CoP within the geographically diverse, multi-disciplinary WATI group using evaluation and social network methodologies. METHODS: A single-group design was employed using a survey of expectations, knowledge, and interpersonal WATI-related relationships administered prior to a meeting of the WATI group followed by a 3-week post-meeting Web survey to assess short-term impact on learning and networking outcomes. RESULTS: Twenty-three of 27 WATI attendees (85%) from diverse disciplinary and practice backgrounds completed the baseline survey, with 21 (91%) of those participants completing the three-week follow-up. Participants had modest expectations of the meeting at baseline. A social network map produced from the data illustrated a centralized, yet sparse network comprising of interdisciplinary teams with little trans-sectoral collaboration. Three-week follow-up survey results showed that participants had made new network connections and had actively engaged in KTE activities with WATI members outside their original network. CONCLUSION: Data illustrating both the shape and size of the WATI network as well as member's interests and commitment to KTE, when shared and used to frame action steps, can positively influence the motivation to collaborate and create communities of practice. Guiding KTE planning through blending data and theory can create more informed transdisciplinary and trans-sectoral collaboration environments