julilili42/papers huggingface dataset:
Driving next-generation autophagy researchers towards translation (DRIVE), an international PhD training program on autophagy
2018-09-03

The European autophagy consortium <i>Driving next-generation autophagy researchers towards translation</i> (DRIVE) held its kick-off meeting in Groningen on the 14<sup>th</sup> and 15<sup>th</sup> of June 2018. This Marie Skłodowska-Curie Early Training Network was approved under the European Union's Horizon 2020 Research and Innovation Program and is funded for 4 years. Within DRIVE, 14 European research teams from academia and industry will train 15 PhD students through applied, cross-disciplinary and collaborative macroautophagy/autophagy research. The goal of DRIVE is to stimulate applied approaches in autophagy research and provide training towards translation, while advancing our knowledge on autophagy in specific physiological and pathological states. The strong focus on translation will prepare the PhD students to be at the forefront to exploit autophagy for the development of therapies directly benefitting patients. Thereby, DRIVE will contribute to filling the educational gap that currently exists between academia and industry, and will prepare its PhD students for alternative and highly flexible professional paths.
How steady are steady-state mountain belts? – a re-examination of the Olympic Mountains (Washington State, USA)
2018-09-03

Abstract. The Olympic Mountains of Washington State (USA) represent the aerially exposed accretionary wedge of the Cascadia subduction zone and are thought to be in flux steady-state, whereby the mass outflux (denudation) and influx (tectonic accretion) into the mountain range are balanced. We use a multi-method approach to investigate how temporal variations in the influx and outflux could affect previous interpretations of flux steady-state. This includes published and new thermochronometric ages for (U-Th)/He dating of apatite and zircon (AHe and ZHe, respectively) and fission track dating of apatite and zircon (AFT and ZFT, respectively), 1D thermo-kinematic modelling of thermochronometric data and independent estimates of outflux and influx. We present 61 new thermochronometric ages. AHe ages are generally young ( 2 km/Myr to 1 km/Myr. This demonstrates that the material outflux is varying through time, requiring a commensurate variation in influx to maintain flux steady-state. Evaluation of the offshore and onshore sediment record shows, that the material influx is also variable through time and that the amount of sediment residing in the wedge is spatially variable. Our quantitative assessment of influx and outflux indicates that the Olympic Mountains could be in flux steady-state on long timescales (107 yr), but significant perturbations of steady-state occur on shorter timescales (105–106 yr), e.g., during the Plio-Pleistocene glaciation.
RXFP1 Receptor Activation by Relaxin-2 Induces Vascular Relaxation in Mice via a Gαi2-Protein/PI3Kß/γ/Nitric Oxide-Coupled Pathway
2018-09-04

Background: Relaxins are small peptide hormones, which are novel candidate molecules that play important roles in cardiometablic syndrome. Relaxins are structurally related to the insulin hormone superfamily, which provide vasodilatory effects by activation of G-protein-coupled relaxin receptors (RXFPs) and stimulation of endogenous nitric oxide (NO) generation. Recently, relaxin could be demonstrated to activate G(i) proteins and phosphoinositide 3-kinase (PI3K) pathways in cultured endothelial cells in vitro. However, the contribution of the G(i)-PI3K pathway and their individual components in relaxin-dependent relaxation of intact arteries remains elusive. Methods: We used G alpha(i2)- (Gnai2(-/-)) and G alpha(i3)-deficient (Gnai3(-/-)) mice, pharmacological tools and wire myography to study G-protein-coupled signaling pathways involved in relaxation of mouse isolated mesenteric arteries by relaxins. Human relaxin-1, relaxin-2, and relaxin-3 were tested. Results: Relaxin-2 (similar to 50% relaxation at 10(-11) M) was the most potent vasodilatory relaxin in mouse mesenteric arteries, compared to relaxin-1 and relaxin-3. The vasodilatory effects of relaxin-2 were inhibited by removal of the endothelium or treatment of the vessels with N (G)-nitro-L-arginine methyl ester (L-NAME, endothelial nitric oxide synthase (eNOS) inhibitor) or simazine (RXFP1 inhibitor). The vasodilatory effects of relaxin-2 were absent in arteries of mice treated with pertussis toxin (PTX). They were also absent in arteries isolated from Gnai2(-/-) mice, but not from Gnai3(-/-) mice. The effects were not affected by FR900359 (G alpha(q) protein inhibitor) or PI-103 (PI3K alpha inhibitor), but inhibited by TGX-221 (PI3K beta inhibitor) or AS-252424 (PI3K gamma inhibitor). Simazine did not influence the anti-contractile effect of perivascular adipose tissue. Conclusion: Our data indicate that relaxin-2 produces endothelium- and NO-dependent relaxation of mouse mesenteric arteries by activation of RXFP1 coupled to G(i2)-PI3K-eNOS pathway. Targeting vasodilatory G(i)-protein-coupled RXFP1 pathways may provide promising opportunities for drug discovery in endothelial dysfunction and cardiometabolic disease.
A Quantile Regression Approach to Estimate the Variance of Financial Returns*
2018-09-04

We propose to estimate the conditional variance of a time series of financial returns through a quantile autoregressive (AR) model and demonstrate that it contains all information commonly captured in two separate equations for the mean and variance of a generalized AR conditional heteroscedasticity-type model. We show that the inter-quantile range spanned by conditional quantile estimates identifies the asymmetric response of volatility to lagged returns, resulting in wider conditional densities for negative returns than for positive returns. Finally, we estimate the conditional variance based on the estimated conditional density and illustrate its accuracy in a forecast evaluation.
Mitral Valve Endocarditis due to Lactobacillus
2018-09-04

Lactobacillus species are Gram-positive, facultative anaerobic, rod-shaped bacteria. They belong to the lactic acid bacteria group and are also known as a usual part of the normal flora of the gastrointestinal tract as well as of the urinary and genital tracts. They are an infrequent human pathogen but can induce several infections such as bacteremia and infectious endocarditis. We report the case of an 81-year-old woman with Lactobacillus bacteremia and mitral valve endocarditis as well as splenic abscesses.
Cholinergic Pathway SNPs and Postural Control in 477 Older Adults
2018-09-04

<b>Objective:</b> To determine whether single nucleotide polymorphisms (SNPs) of the cholinergic system and quantitative parameters of postural control are associated in healthy older adults. This is a cross-sectional analysis from the TREND study. <b>Methods:</b> All participants performed a static postural control task for 30 s on a foam pad in semitandem stance and eyes closed. We analyzed mean power frequency (MPF), area, acceleration, jerk, and velocity from a mobile sensor worn at the lower back using a validated algorithm. Genotypes of four SNPs in genes involved in the cholinergic system (<i>SLC5A7, CHAT, BCHE, CHRNA4</i>) were extracted from the NeuroX chip. All participants present a normal neurological examination and a Minimental state examination score >24. <b>Results:</b> Four hundred and seventy seven participants were included. Mean age was 69 years, 41% were female. One SNP of the cholinergic pathway was significantly associated with a quantitative postural control parameter. The minor allele of rs6542746 in <i>SLC5A7</i> was associated with lower MPF (4.04 vs. 4.22 Hz; <i>p</i> = 3.91 × 10<sup>-4</sup>). Moreover, the following associations showed trends toward significance: minor allele of rs6542746 in <i>SLC5A7</i> with higher anteroposterior acceleration (318 vs. 287 mG; <i>p</i> = 0.005), and minor allele of rs3810950 in <i>CHAT</i> with higher mediolateral acceleration [1.77 vs. 1.65 log(mG); <i>p</i> = 0.03] and velocity [1.83 vs. 1.74 log(mm/s); <i>p</i> = 0.019]. Intraindividual occurrence of rs6542746 and rs3810950 minor alleles was dose-dependently related with lower MPF (<i>p</i> = 0.004). <b>Conclusion:</b> This observational study suggests an influence of SNPs of the cholinergic pathway on postural control in older adults.
Quantum-enhanced measurements without entanglement
2018-09-05

Quantum-enhanced measurements exploit quantum mechanical effects for increasing the sensitivity&#13;\\nof measurements of certain physical parameters and have great potential for both fundamental science&#13;\\nand concrete applications. Most of the research has so far focused on using highly entangled states,&#13;\\nwhich are, however, difficult to produce and to stabilize for a large number of constituents. In the&#13;\\nfollowing alternative mechanisms are reviewed, notably the use of more general quantum correlations&#13;\\nsuch as quantum discord, identical particles, or nontrivial Hamiltonians; the estimation of&#13;\\nthermodynamical parameters or parameters characterizing nonequilibrium states; and the use of&#13;\\nquantum phase transitions. Both theoretically achievable enhancements and enhanced sensitivities not&#13;\\nprimarily based on entanglement that have already been demonstrated experimentally and indicate&#13;\\nsome possible future research directions are described.
Accretion heated atmospheres of X-ray bursting neutron stars
2018-09-05

Some thermonuclear (type I) X-ray bursts at the neutron star surfaces in low-mass X-ray binaries take place during hard persistent states of the systems. Spectral evolution of these bursts is well described by the atmosphere model of a passively cooling neutron star when the burst luminosity is high enough. The observed spectral evolution deviates from the model predictions when the burst luminosity drops below a critical value of 20–70% of the maximum luminosity. The amplitude of the deviations and the critical luminosity correlate with the persistent luminosity, which leads us to suggest that these deviations are induced by the additional heating of the accreted particles. We present a method for computation of the neutron star atmosphere models heated by accreted particles assuming that their energy is released via Coulomb interactions with electrons. We computed the temperature structures and the emergent spectra of the atmospheres of various chemical compositions and investigate the dependence of the results on the velocity of accreted particles, their temperature and the penetration angle. We show that the heated atmosphere develops two different regions. The upper one is the hot (20–100 keV) corona-like surface layer cooled by Compton scattering, and the deeper, almost isothermal optically thick region with a temperature of a few keV. The emergent spectra correspondingly have two components: a blackbody with the temperature close to that of the isothermal region and a hard Comptonized component (a power law with an exponential decay). Their relative contribution depends on the ratio of the energy dissipation rate of the accreted particles to the intrinsic flux from the neutron star surface. These spectra deviate strongly from those of undisturbed, passively cooling neutron star atmospheres, with the main differences being the presence of a high-energy tail and a strong excess in the low-energy part of the spectrum. They also lack the iron absorption edge, which is visible in the spectra of undisturbed low-luminosity atmospheres with solar chemical composition. Using the computed spectra, we obtained the dependences of the dilution and color-correction factors as functions of relative luminosities for pure helium and solar abundance atmospheres. We show that the helium model atmosphere heated by accretion corresponding to 5% of the Eddington luminosity describes well the late stages of the X-ray bursts in 4U 1820−30.
Sleep Strengthens Predictive Sequence Coding
2018-09-05

Predictive-coding theories assume that perception and action are based on internal models derived from previous experience. Such internal models require selection and consolidation to be stored over time. Sleep is known to support memory consolidation. We hypothesized that sleep supports both consolidation and abstraction of an internal task model that is subsequently used to predict upcoming stimuli. Human subjects (of either sex) were trained on deterministic visual sequences and tested with interleaved deviant stimuli after retention intervals of sleep or wakefulness. Adopting a predictive-coding approach, we found increased prediction strength after sleep, as expressed by increased error rates to deviant stimuli, but fewer errors for the immediately following standard stimuli. Sleep likewise enhanced the formation of an abstract sequence model, independent of the temporal context during training. Moreover, sleep increased confidence for sequence knowledge, reflecting enhanced metacognitive access to the model. Our results suggest that sleep supports the formation of internal models which can be used to predict upcoming events in different contexts. SIGNIFICANCE STATEMENT To efficiently interact with the ever-changing world, we predict upcoming events based on similar previous experiences. Sleep is known to benefit memory consolidation. However, it is not clear whether sleep specifically supports the transformation of past experience into predictions of future events. Here, we find that, when human subjects sleep after learning a sequence of predictable visual events, they make better predictions about upcoming events compared with subjects who stayed awake for an equivalent period of time. In addition, sleep supports the transfer of such knowledge between different temporal contexts (i.e., when sequences unfold at different speeds). Thus, sleep supports perception and action by enhancing the predictive utility of previous experiences.
Application of Diagnostic Tools to Evaluate Remediation Performance at Petroleum Hydrocarbon‐Impacted Sites
2018-09-05

Abstract In situ treatment technologies for petroleum hydrocarbon‐impacted sites (e.g., multiphase extraction, air sparging, soil vapor extraction, or in situ chemical oxidation) usually rely on a specific chemical, microbial, or physical contaminant removal process. However, target contaminant concentrations can also vary due to other co‐occurring processes (e.g. delivery of remedial fluids, natural variability), which can confound the ability to demonstrate treatment efficiency. This technical note proposes a methodology that integrates several diagnostic tools to assess treatment performance. Stable isotope methods and biomarkers were selected because they provide process‐specific and, often, also compound‐specific information on contaminant removal. The isotope tools include compound‐specific isotope analysis that can be used to discriminate between a broad range of removal processes, and isotope analysis of oxidants and degradation end products to assess overall transformation of hydrocarbons. The biomarkers cover characteristic metabolites and functional genes on a mRNA rather than DNA level to understand biological activity more carefully. This technical note integrates information from laboratory and field studies, especially controlled‐field experiments where the tools have been evaluated side‐by‐side for different treatment methods. A tiered approach is proposed to deploy the tools in a stepwise manner until sufficient information is obtained to confidently identify the mass removal processes of interest and demonstrate efficacy of the intended treatment mechanism. The order of tool application considers the type of information that can be gained, the level of certainty, and the ease of implementation. The objective of this technical note is to enable widespread use of these diagnostic tools with the motivation to improve the efficacy of in situ treatment systems.
Illegitimate authorship and flawed procedures: Fundamental, formal criticisms of the Declaration of Helsinki
2018-09-05

Abstract Some of the recent criticisms published during and after the last revision process of the Declaration of Helsinki are directed at its basic legitimacy. In this article we want to have a closer look at the two criticisms we consider to be the most fundamental. The first criticism questions the legitimate authorship of the World Medical Association to publish a document such as the Declaration. The second fundamental criticism we want to examine argues that the last revision process failed to meet the standards for fair, democratic procedures. Although both criticisms deny the formal legitimacy of the Declaration in the most fundamental way, they have never been addressed in detail in a single article. We refute most of the related arguments. However, acknowledging some of the points made, improvements for future revision processes and versions of the Declaration of Helsinki are outlined.
Flesh and bone: An integrative approach towards sexual size dimorphism of a terrestrial salamander (genus Salamandrina)
2018-09-05

Abstract Males and females face different selection pressures due to a sexually biased investment into reproduction. This often results in different morphologies. Sexual size dimorphisms (SSD) can give us important hints on the evolution and biology of a species. Salamanders are a perfectly suited system for investigating SSD, including a diversity of reproductive modes and behaviors, and patterns of SSD combined with life history traits in a phylogenetic context help us to understand the evolution of these processes. Because spectacled salamanders (genus Salamandrina ) are the phylogenetically most basal taxon of the Salamandridae, they play a key role in reconstructing the evolutionary pattern of SSD. Combining extensive external and skeletal measurements of the cranium, limbs, and the pelvic girdle using high‐resolution micro Computer Tomography (μCT) yielded an integrative analysis of expressed SSD of morphology and osteology of Salamandrina perspicillata . Multivariate analysis of external characters showed that males generally had larger cloacae, heads, and limbs relative to body size, while females had larger trunks. Analysis of osteology confirmed this pattern but also revealed new dimorphic characters in the cranium and the pelvic girdle. Dimorphic characters in external morphology and osteology are likely linked to the different reproductive roles of the sexes and support sexual rather than ecological selection as the primary force acting on the phenotype of the phylogenetically basal salamandrids.
Message in a bottle: Spontaneous phase separation of hydrous Vesuvius melt even at low decompression rates
2018-09-06

Violent explosive volcanic eruptions are destructive and threaten millions of people and infrastructure. Ejected ash, pumice and gases are end-products of volcanic factories sourced deep within magma chambers and conduits. The different production stages are not directly observable. However, experimental simulation reveals different stages of dynamic volcanic processes. The starting point of explosive volcanic eruptions is determined by the phase separation of an H2O fluid from a supersaturated hydrous silicate melt. The number of formed H2O fluid vesicles per unit volume of silicate melt (VND) is a basic property that controls the efficiency of fluid-melt separation, ascent velocity and finally explosive volcanism. We performed decompression experiments at superliquidus temperatures to simulate phase separation of a single phase hydrous silicate melt during ascent with AD79 Vesuvius white pumice composition using decompression rates of 0.024–1.7 MPa⋅s−1. The white pumice buried Herculaneum and Pompeii and is representative of other catastrophic phonolitic and trachytic explosive eruptions like the violent 39 ka Campi Flegrei and the 1815 AD Tambora eruption. Here we report a high log⁡VND of 5.2 (in mm−3) that is independent from decompression rate within the investigated range. Even at a decompression rate of 0.024 MPa⋅s−1 the formation of a high VND inevitably causes rapid degassing due to short H2O diffusion distances from the melt into fluid vesicles. A decompression rate meter based on nucleation theory, which is commonly used to estimate magma ascent velocity during volcanic eruptions using VND of volcanic ejecta, cannot be adapted to explain our experimentally determined decompression rate independent VND. Alternatively, decompression induced H2O–silicate melt phase separation may be described by diffusion controlled spinodal decomposition where maximum supersaturation is reached. This process occurs spontaneously and free of activation energy if hydrous melt is driven into thermodynamic instability where the second derivative of free energy of mixing to the H2O content is ≤0. However, the decompression rate independent VND has profound consequences for the dynamics of natural polyphase hydrous magma phase separation. Even at low ascent rates spontaneous hydrous melt phase separation facilitates rapid density decrease accompanied by sudden increase of magma buoyancy triggering explosive eruptions.
cGMP-dependent protein kinase I (cGKI) modulates human hepatic stellate cell activation
2018-09-06

These results suggest that the lack of cGKI possibly leads to stellate cell activation, which stimulates chemokine expression and activates inflammatory processes, which could disturb hepatic insulin sensitivity.
PORTRAITS OF A PARTHIAN KING: ROCK-RELIEFS AND THE MOUNTAIN FORTRESSES OF RABANA-MERQULY IN IRAQI KURDISTAN
2018-09-06

This article presents detailed illustrations of two rock-reliefs from the neighbouring sites Rabana and Merquly, located on the flanks of Mt. Piramagrun in Iraqi Kurdistan. Both matching sculptures are aligned with perimeter fortifications that enclose substantial architectural remains. Based on numismatic parallels, supported by archaeological evidence, it is proposed that these depictions of near life-size figures represent an anonymous Arsacid King of Kings from the early first millennium ( c . a.d. 50-150), who was credited with construction of the mountain fortresses. Rabana and Merquly together form an important landscape of settlement on the north-western frontier of the Parthian Empire.
Bayesian Hypothesis Testing And Experimental Design For Two-Photon Imaging Data
2018-09-06

Abstract Variability, stochastic or otherwise, is a central feature of neural circuits. Yet the means by which variation and uncertainty are derived from noisy observations of neural activity is often unprincipled, with too much weight placed on numerical convenience at the cost of statistical rigour. For two-photon imaging data, composed of fundamentally probabilistic streams of photon detections, the problem is particularly acute. Here, we present a complete statistical pipeline for the inference and analysis of neural activity using Gaussian Process Regression, applied to two-photon recordings of light-driven activity in ex vivo mouse retina. We demonstrate the flexibility and extensibility of these models, considering cases with non-stationary statistics, driven by complex parametric stimuli, in signal discrimination, hierarchical clustering and inference tasks. Sparse approximation methods allow these models to be fitted rapidly, permitting them to actively guiding the design of light stimulation in the midst of ongoing two-photon experiments.