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Hypomagnesemia affects insulin resistance and is a risk factor for diabetes mellitus type 2 (DM2) and gestational diabetes mellitus (GDM). Two single nucleotide polymorphisms (SNPs) in the epithelial magnesium channel TRPM6 ((VI)-I-1393, (KE)-E-1584) were predicted to confer susceptibility for DM2. Here, we show using patch clamp analysis and total internal reflection fluorescence microscopy, that insulin stimulates TRPM6 activity via a phosphoinositide 3-kinase and Rac1-mediated elevation of cell surface expression of TRPM6. Interestingly, insulin failed to activate the genetic variants TRPM6 ((VI)-I-1393) and TRPM6((KE)-E-1584), which is likely due to the inability of the insulin signaling pathway to phosphorylate TRPM6(T-1391) and TRPM6(S-1583). Moreover, by measuring total glycosylated hemoglobin (TGH) in 997 pregnant women as a measure of glucose control, we demonstrate that TRPM6((VI)-I-1393) and TRPM6((KE)-E-1584) are associated with higher TGH and confer a higher likelihood of developing GDM. The impaired response of TRPM6((VI)-I-1393) and TRPM6((KE)-E-1584) to insulin represents a unique molecular pathway leading to GDM where the defect is located in TRPM6.
Triassic Latemar cycle tops - Subaerial exposure of platform carbonates under tropical arid climate
(2012)
The Triassic Latemar platform in the Dolomites, Italy, is the site of several ongoing controversies. Perhaps the most interesting debate focuses on apparent cyclic deposition within the Latemar platform, whose nature and duration are still open to debate. Further disagreement concerns the lack of meteoric diagenesis-related isotope shifts at cycle tops that bear circumstantial petrographic evidence for subaerial emergence. Here, an evaluation of the nature of Latemar cycle tops is presented combining evidence from previous work and new field, petrographic and geochemical data. Cycle tops are ranked according to increasing exposure duration and spatial extent: type I surfaces lacking unequivocal evidence of prolonged supratidal conditions; type II dolomite caps formed in warm, evaporitic, intertidal lagoonal waters followed by exposure of perhaps intermediate duration; type III clastic-rich, red calcareous horizons with some showing platform-wide extent, representing prolonged supratidal conditions, and type IV discontinuities in tepee belts, genetically related to type II and III surfaces, but likely representing shorter-lived exposure stages. Petrographic and geochemical criteria indicate that most diagenesis occurred in the shallow marine and burial domain whilst an extensive meteoric overprint of cycle tops is lacking. This is underlined by the scarcity of meteoric diagenetic fabrics such as gravitational cements that, where present, are here interpreted as marine-vadose in origin. The scarcity of carbon and oxygen isotope signatures commonly assigned to subaerial exposure stages is best explained in the context of mid-Triassic climate. The low latitude, tropical but arid setting of the Latemar, situated in the western extension of the Tethys ocean, its isolation from nearby continental areas and overall short-term emergence episodes are in agreement with a limited degree of meteoric alteration of most cycle tops. High amounts of aeolian clastic material beneath some cycle tops, along with high Fe and Mn elemental abundances argue for intermittent subaerial conditions. This study proposes an enhancement of the classical Allan and Matthews (1982) isotope model for subaerial exposure under strongly arid climates. As the subaerial exposure nature of Latemar cycle tops, and therefore eustasy as the cause for cyclicity, have been previously challenged due to the lack of meteoric-induced isotopic signatures, the outcome of this study is of significance for the ongoing Latemar stratigraphic controversy.
Away from active plate boundaries the relationships between spatiotemporal variations in density and geothermal gradient are important for understanding the evolution of topography in continental interiors. In this context the classic concept of the continental lithosphere as comprising three static layers of different densities (upper crust, lower crust, and upper mantle) is not adequate to assess long-term changes in topography and relief in regions associated with pronounced thermal anomalies in the mantle. We have therefore developed a one-dimensional model, which is based on thermodynamic equilibrium assemblage computations and deliberately excludes the effects of melting processes like intrusion or extrusions. Our model calculates the "metamorphic density" of rocks as a function of pressure, temperature, and chemical composition. It not only provides a useful tool for quantifying the influence of petrologic characteristics on density, but also allows the modeled "metamorphic" density to be adjusted to variable geothermal gradients and applied to different geodynamic environments. We have used this model to simulate a scenario in which the lithosphere-asthenosphere boundary is subjected to continuous heating over a long period of time (130 Ma), and demonstrate how an anorogenic plateau with an elevation of 1400 m can be formed solely as a result of heat transfer within the continental lithosphere. Our results show that, beside dynamic topography (of asthenospheric origin), density changes within the lithosphere have an important impact on the evolution of anorogenic plateaus.
Both aftershocks and geodetically measured postseismic displacements are important markers of the stress relaxation process following large earthquakes. Postseismic displacements can be related to creep-like relaxation in the vicinity of the coseismic rupture by means of inversion methods. However, the results of slip inversions are typically non-unique and subject to large uncertainties. Therefore, we explore the possibility to improve inversions by mechanical constraints. In particular, we take into account the physical understanding that postseismic deformation is stress-driven, and occurs in the coseismically stressed zone. We do joint inversions for coseismic and postseismic slip in a Bayesian framework in the case of the 2004 M6.0 Parkfield earthquake. We perform a number of inversions with different constraints, and calculate their statistical significance. According to information criteria, the best result is preferably related to a physically reasonable model constrained by the stress-condition (namely postseismic creep is driven by coseismic stress) and the condition that coseismic slip and large aftershocks are disjunct. This model explains 97% of the coseismic displacements and 91% of the postseismic displacements during day 1-5 following the Parkfield event, respectively. It indicates that the major postseismic deformation can be generally explained by a stress relaxation process for the Parkfield case. This result also indicates that the data to constrain the coseismic slip model could be enriched postseismically. For the 2004 Parkfield event, we additionally observe asymmetric relaxation process at the two sides of the fault, which can be explained by material contrast ratio across the fault of similar to 1.15 in seismic velocity.
One of the main milestones in the study of opto- and electromechanical systems is to certify entanglement between a mechanical resonator and an optical or microwave mode of a cavity field. In this work, we show how a suitable time-periodic modulation can help to achieve large degrees of entanglement, building upon the framework introduced in Mari and Eisert (2009 Phys. Rev. Lett. 103 213603). It is demonstrated that with suitable driving, the maximum degree of entanglement can be significantly enhanced, in a way exhibiting a nontrivial dependence on the specifics of the modulation. Such time-dependent driving might help to experimentally achieve entangled mechanical systems also in situations when quantum correlations are otherwise suppressed by thermal noise.
We report on very high energy (E > 100 GeV) gamma-ray observations of V407 Cygni, a symbiotic binary that underwent a nova outburst producing 0.1-10 GeV gamma rays during 2010 March 10-26. Observations were made with the Very Energetic Radiation Imaging Telescope Array System during 2010 March 19-26 at relatively large zenith angles due to the position of V407 Cyg. An improved reconstruction technique for large zenith angle observations is presented and used to analyze the data. We do not detect V407 Cygni and place a differential upper limit on the flux at 1.6 TeV of 2.3 x 10(-12) erg cm(-2) s(-1) (at the 95% confidence level). When considered jointly with data from Fermi-LAT, this result places limits on the acceleration of very high energy particles in the nova.
We investigate the effect of intermode coupling and anharmonicity on the excitation and relaxation dynamics of CO on Cu(100). The nonadiabatic coupling of the adsorbate to the surface is treated perturbatively using a position-dependent state-resolved transition rate model. Using the potential energy surface of Marquardt et al. [J. Chem. Phys. 132, 074108 (2010)], which provides an accurate description of intermode interactions, we propose a four-dimensional model that represents simultaneously the diffusion and the desorption of the adsorbate. The system is driven by both rational and optimized infrared laser pulses to favor either selective mode and state excitations or lateral displacement along the diffusion coordinate. The dissipative dynamics is simulated using the reduced density matrix in its Lindblad form. We show that coupling between the degrees of freedom, mediated by the creation and annihilation of electron-hole pairs in the metal substrate, significantly affects the system excitation and relaxation dynamics. In particular, the angular degrees of freedom appear to play an important role in the energy redistribution among the molecule-surface vibrations. We also show that coherent excitation using simple IR pulses can achieve population transfer to a specific target to some extent but does not allow enforcement of the directionality to the diffusion motion.
Background: Dopamine plays an important role in orienting and the regulation of selective attention to relevant stimulus characteristics. Thus, we examined the influences of functional variants related to dopamine inactivation in the dopamine transporter (DAT1) and catechol-O-methyltransferase genes (COMT) on the time-course of visual processing in a contingent negative variation (CNV) task.
Methods: 64-channel EEG recordings were obtained from 195 healthy adolescents of a community-based sample during a continuous performance task (A-X version). Early and late CNV as well as preceding visual evoked potential components were assessed.
Results: Significant additive main effects of DAT1 and COMT on the occipito-temporal early CNV were observed. In addition, there was a trend towards an interaction between the two polymorphisms. Source analysis showed early CNV generators in the ventral visual stream and in frontal regions. There was a strong negative correlation between occipito-temporal visual post-processing and the frontal early CNV component. The early CNV time interval 500-1000 ms after the visual cue was specifically affected while the preceding visual perception stages were not influenced.
Conclusions: Late visual potentials allow the genomic imaging of dopamine inactivation effects on visual post-processing. The same specific time-interval has been found to be affected by DAT1 and COMT during motor post-processing but not motor preparation. We propose the hypothesis that similar dopaminergic mechanisms modulate working memory encoding in both the visual and motor and perhaps other systems.
Landslides are a hazard for humans and artificial structures. From an ecological point of view, they represent an important ecosystem disturbance, especially in tropical montane forests. Here, shallow translational landslides are a frequent natural phenomenon and one local determinant of high levels of biodiversity. In this paper, we apply weighted ensembles of advanced phenomenological models from statistics and machine learning to analyze the driving factors of natural landslides in a tropical montane forest in South Ecuador. We exclusively interpret terrain attributes, derived from a digital elevation model, as proxies to several driving factors of landslides and use them as predictors in our models which are trained on a set of five historical landslide inventories. We check the model generality by transferring them in time and use three common performance criteria (i.e. AUC, explained deviance and slope of model calibration curve) to, on the one hand, compare several state-of-the-art model approaches and on the other hand, to create weighted model ensembles. Our results suggest that it is important to consider more than one single performance criterion.
Approaching our main question, we compare responses of weighted model ensembles that were trained on distinct functional units of landslides (i.e. initiation, transport and deposition zones). This way, we are able to show that it is quite possible to deduce driving factors of landslides, if the consistency between the training data and the processes is maintained. Opening the 'black box' of statistical models by interpreting univariate model response curves and relative importance of single predictors regarding their plausibility, we provide a means to verify this consistency.
With the exception of classification tree analysis, all techniques performed comparably well in our case study while being outperformed by weighted model ensembles. Univariate response curves of models trained on distinct functional units of landslides exposed different shapes following our expectations. Our results indicate the occurrence of landslides to be mainly controlled by factors related to the general position along a slope (i.e. ridge, open slope or valley) while landslide initiation seems to be favored by small scale convexities on otherwise plain open slopes.
Propagation rate coefficients for homogeneous phase VDF-HFP copolymerization in supercritical CO2
(2012)
For the first time, propagation rate coefficients, kp,COPO, for the copolymerizations of vinylidene fluoride and hexafluoropropene have been determined. The kinetic data was determined via pulsed-laser polymerization in conjunction with polymer analysis via size-exclusion chromatography, the PLP-SEC technique. The experiments were carried out in homogeneous phase with supercritical CO2 as solvent for temperatures ranging from 45 to 90 degrees C. Absolute polymer molecular weights were calculated on the basis of experimentally determined MarkHouwink constants. The Arrhenius parameters of kp,COPO vary significantly compared with ethene, which is explained by the high electronegativity of fluorine and less intra- and intermolecular interactions between the partially fluorinated macroradicals.