An in silico MS/MS library for automatic annotation of novel FAHFA lipids.

BackgroundA new lipid class named 'fatty acid esters of hydroxyl fatty acids' (FAHFA) was recently discovered in mammalian adipose tissue and in blood plasma and some FAHFAs were found to be associated with type 2 diabetes. To facilitate the automatic annotation of FAHFAs in biological specimens, a tandem mass spectra (MS/MS) library is needed. Due to the limitation of the commercial available standard compounds, we proposed building an in silico MS/MS library to extend the coverage of molecules.ResultsWe developed a computer-generated library with 3267 tandem mass spectra (MS/MS) for 1089 FAHFA species. FAHFA spectra were generated based on authentic standards with negative mode electrospray ionization and 10, 20, and 40 V collision induced dissociation at 4 spectra/s as used in in ultra-high performance liquid chromatography-QTOF mass spectrometry studies. However, positional information of the hydroxyl group is only obtained either at lower QTOF spectra acquisition rates of 1 spectrum/s or at the MS(3) level in ion trap instruments. Therefore, an additional set of 4290 fragment-rich MS/MS spectra was created to enable distinguishing positional FAHFA isomers. The library was generated based on ion fragmentations and ion intensities of FAHFA external reference standards, developing a heuristic model for fragmentation rules and extending these rules to large swaths of computer-generated structures of FAHFAs with varying chain lengths, degrees of unsaturation and hydroxyl group positions. Subsequently, we validated the new in silico library by discovering several new FAHFA species in egg yolk, showing that this library enables high-throughput screening of FAHFA lipids in various biological matrices.ConclusionsThe developed library and templates are freely available for commercial or noncommercial use at http://fiehnlab.ucdavis.edu/staff/yanma/fahfa-lipid-library. This in silico MS/MS library allows users to annotate FAHFAs from accurate mass tandem mass spectra in an easy and fast manner with NIST MS Search or PepSearch software. The developing template is provided for advanced users to modify the parameters and export customized libraries according to their instrument features. Graphical abstractExample of experimental and in silico MS/MS spectra for FAHFA lipids

Structure of the upper mantle in the north-western and central United States from USArray S-receiver functions

We used more than 40 000 S-receiver functions recorded by the USArray project to study the structure of the upper mantle between the Moho and the 410 km discontinuity from the Phanerozoic western United States to the cratonic central US. In the western United States we observed the lithosphere–asthenosphere boundary (LAB), and in the cratonic United States we observed both the mid-lithospheric discontinuity (MLD) and the LAB of the craton. In the northern and southern United States the western LAB almost reaches the mid-continental rift system. In between these two regions the cratonic MLD is surprisingly plunging towards the west from the Rocky Mountain Front to about 200 km depth near the Sevier thrust belt. We interpret these complex structures of the seismic discontinuities in the mantle lithosphere as an indication of interfingering of the colliding Farallon and Laurentia plates. Unfiltered S-receiver function data reveal that the LAB and MLD are not single discontinuities but consist of many small-scale laminated discontinuities, which only appear as single discontinuities after longer period filtering. We also observe the Lehmann discontinuity below the LAB and a velocity reduction about 30 km above the 410 km discontinuity

Ambient vibration measurements in the Southern Rhine Graben close to Basle

This study presents results of ambient noise measurements from temporary single station and small-scale array deployments in the northeast of Basle. H/V spectral ratios were determined along various profiles crossing the eastern masterfault of the Rhine Rift Valley and the adjacent sedimentary rift fills. The fundamental H/V peak frequencies are decreasing along the profile towards the eastern direction being consistent with the dip of the tertiary sediments within the rift. Using existing empirical relationships between H/V frequency peaks and the depth of the dominant seismic contrast, derived on basis of the ?/4-resonance hypothesis and a power law depth dependence of the S-wave velocity, we obtain thicknesses of the rift fill from about 155 m in the west to 280 m in the east. This is in agreement with previous studies. The array analysis of the ambient noise wavefield yielded a stable dispersion relation consistent with Rayleigh wave propagation velocities. We conclude that a significant amount of surface waves is contained in the observed wavefield. The computed ellipticity for fundamental mode Rayleigh waves for the velocity depth models used for the estimation of the sediment thicknesses is in agreement with the observed H/V spectra over a large frequency band

Receiver function images of the Hellenic subduction zone and comparison to microseismicity

New combined P receiver functions and seismicity data obtained from the EGELADOS network employing 65 seismological stations within the Aegean constrained new information on the geometry of the Hellenic subduction zone. The dense network and large data set enabled us to estimate the Moho depth of the continental Aegean plate across the whole area. Presence of a negative contrast at the Moho boundary indicating the serpentinized mantle wedge above the subducting African plate was seen along the entire forearc. Furthermore, low seismicity was observed within the serpentinized mantle wedge. We found a relatively thick continental crust (30–43 km) with a maximum thickness of about 48 km beneath the Peloponnese Peninsula, whereas a thinner crust of about 27–30 km was observed beneath western Turkey. The crust of the overriding plate is thinning beneath the southern and central Aegean and reaches 23–27 km. Unusual low Vp / Vs ratios were estimated beneath the central Aegean, which most likely represent indications on the pronounced felsic character of the extended continental Aegean crust. Moreover, P receiver functions imaged the subducted African Moho as a strong converted phase down to a depth of about 100 km. However, the converted Moho phase appears to be weak for the deeper parts of the African plate suggesting nearly complete phase transitions of crustal material into denser phases. We show the subducting African crust along eight profiles covering the whole southern and central Aegean. Seismicity of the western Hellenic subduction zone was taken from the relocated EHB-ISC catalogue, whereas for the eastern Hellenic subduction zone, we used the catalogues of manually picked hypocentre locations of temporary networks within the Aegean. Accurate hypocentre locations reveal a significant change in the dip angle of the Wadati–Benioff zone (WBZ) from west (~ 25°) to the eastern part (~ 35°) of the Hellenic subduction zone. Furthermore, a zone of high deformation can be characterized by a vertical offset of about 40 km of the WBZ beneath the eastern Cretan Sea. This deformation zone may separate a shallower N-ward dipping slab in the west from a steeper NW-ward dipping slab in the east. In contrast to hypocentre locations, we found very weak evidence for the presence of the slab at larger depths in the P receiver functions, which may result from the strong appearance of the Moho multiples as well as eclogitization of the oceanic crust. The presence of the top of a strong low-velocity zone at about 60 km depth in the central Aegean may be related to the asthenosphere below the Aegean continental lithosphere and above the subducting slab. Thus, the Aegean mantle lithosphere seems to be 30–40 km thick, which means that its thickness increased again since the removal of the mantle lithosphere about 15 to 35 Ma ago

Performance Measures Using Electronic Health Records: Five Case Studies

Presents the experiences of five provider organizations in developing, testing, and implementing four types of electronic quality-of-care indicators based on EHR data. Discusses challenges, and compares results with those from traditional indicators

Domain-wall dynamics in 4C pyrrhotite at low temperature

Monoclinic 4C pyrrhotite (Fe7S8) is ferrimagnetic due to an ordered defect structure with alternating vacancy and vacancy-free sublattices. Its low-temperature magnetic transition near 35 K is characterized by the distinct increase in coercivity and remanent magnetization. The increase of these parameters has been attributed to changes in the domain wall structure. We present static and dynamic magnetization data of a powder sample to study the domain-wall dynamics across the low-temperature transition. The amplitude-dependent ac susceptibility and the ferromagnetic resonance spectroscopy indicate that the hardening of the domain-wall pinning at the transition occurs simultaneously with the decrease in initial saturation remanent magnetization. These two effects are explained by the enhanced inhomogeneity of the bulk material caused by the persistency of the ordered vacancies and by newly formed defects due to localized distortion of Fe(II) sites in the vacancy-free sublattice. The generated localized defects are the link between the domain wall dynamics and the low-temperature transition in 4C pyrrhotit

Connected Network of Minima as a Model Glass: Long Time Dynamics

A simple model to investigate the long time dynamics of glass-formers is presented and applied to study a Lennard-Jones system in supercooled and glassy phases. According to our model, the point representing the system in the configurational phase space performs harmonic vibrations around (and activated jumps between) minima pertaining to a connected network. Exploiting the model, in agreement with the experimental results, we find evidence for: i) stretched relaxational dynamics; ii) a strong T-dependence of the stretching parameter; iii) breakdown of the Stokes-Einstein law.Comment: 4 pages (Latex), 4 eps figure

Potential Energy Landscape and Long Time Dynamics in a Simple Model Glass

We analyze the properties of a Lennard-Jones system at the level of the potential energy landscape. After an exhaustive investigation of the topological features of the landscape of the systems, obtained studying small size sample, we describe the dynamics of the systems in the multi-dimensional configurational space by a simple model. This consider the configurational space as a connected network of minima where the dynamics proceeds by jumps described by an appropriate master equation. Using this model we are able to reproduce the long time dynamics and the low temperature regime. We investigate both the equilibrium regime and the off-equilibrium one, finding those typical glassy behavior usually observed in the experiments such as: {\it i)} stretched exponential relaxation, {\it ii)} temperature-dependent stretching parameter, {\it iii)} breakdown of the Stokes-Einstein relation, and {\it iv)} appearance of a critical temperature below which one observes deviation from the fluctuation-dissipation relation as consequence of the lack of equilibrium in the system.Comment: 11 pages (Latex), 9 ps figure