The modern understanding of sleep is based on the classification of sleep into stages defined by their electroencephalography (EEG) signatures, but the underlying brain dynamics remain unclear. Here ...we aimed to move significantly beyond the current state-of-the-art description of sleep, and in particular to characterise the spatiotemporal complexity of whole-brain networks and state transitions during sleep. In order to obtain the most unbiased estimate of how whole-brain network states evolve through the human sleep cycle, we used a Markovian data-driven analysis of continuous neuroimaging data from 57 healthy participants falling asleep during simultaneous functional magnetic resonance imaging (fMRI) and EEG. This Hidden Markov Model (HMM) facilitated discovery of the dynamic choreography between different whole-brain networks across the wake-non-REM sleep cycle. Notably, our results reveal key trajectories to switch within and between EEG-based sleep stages, while highlighting the heterogeneities of stage N1 sleep and wakefulness before and after sleep.
ABSTRACT
We present results from the search for a stochastic gravitational-wave background (GWB) as predicted by the theory of General Relativity using six radio millisecond pulsars from the Data ...Release 2 (DR2) of the European Pulsar Timing Array (EPTA) covering a timespan up to 24 yr. A GWB manifests itself as a long-term low-frequency stochastic signal common to all pulsars, a common red signal (CRS), with the characteristic Hellings-Downs (HD) spatial correlation. Our analysis is performed with two independent pipelines, ENTERPRISE, and TEMPONEST+FORTYTWO, which produce consistent results. A search for a CRS with simultaneous estimation of its spatial correlations yields spectral properties compatible with theoretical GWB predictions, but does not result in the required measurement of the HD correlation, as required for GWB detection. Further Bayesian model comparison between different types of CRSs, including a GWB, finds the most favoured model to be the common uncorrelated red noise described by a power law with $A = 5.13_{-2.73}^{+4.20} \times 10^{-15}$ and $\gamma = 3.78_{-0.59}^{+0.69}$ (95 per cent credible regions). Fixing the spectral index to γ = 13/3 as expected from the GWB by circular, inspiralling supermassive black hole binaries results in an amplitude of $A =2.95_{-0.72}^{+0.89} \times 10^{-15}$. We implement three different models, BAYESEPHEM, LINIMOSS, and EPHEMGP, to address possible Solar system ephemeris (SSE) systematics and conclude that our results may only marginally depend on these effects. This work builds on the methods and models from the studies on the EPTA DR1. We show that under the same analysis framework the results remain consistent after the data set extension.
Wind-driven upwelling in the ocean around Antarctica helps regulate the exchange of carbon dioxide (CO2) between the deep sea and the atmosphere, as well as the supply of dissolved silicon to the ...euphotic zone of the Southern Ocean. Diatom productivity south of the Antarctic Polar Front and the subsequent burial of biogenic opal in underlying sediments are limited by this silicon supply. We show that opal burial rates, and thus upwelling, were enhanced during the termination of the last ice age in each sector of the Southern Ocean. In the record with the greatest temporal resolution, we find evidence for two intervals of enhanced upwelling concurrent with the two intervals of rising atmospheric CO2 during deglaciation. These results directly link increased ventilation of deep water to the deglacial rise in atmospheric CO2.
1-2-(2,4-Dimethylphenyl-sulfanyl)-phenyl-piperazine (Lu AA21004) is a human (h) serotonin (5-HT)(3A) receptor antagonist (K(i) = 3.7 nM), h5-HT(7) receptor antagonist (K(i) = 19 nM), h5-HT(1B) ...receptor partial agonist (K(i) = 33 nM), h5-HT(1A) receptor agonist (K(i) = 15 nM), and a human 5-HT transporter (SERT) inhibitor (K(i) = 1.6 nM) (J Med Chem 54:3206-3221, 2011). Here, we confirm that Lu AA21004 is a partial h5-HT(1B) receptor agonist EC(50) = 460 nM, intrinsic activity = 22% using a whole-cell cAMP-based assay and demonstrate that Lu AA21004 is a rat (r) 5-HT(7) receptor antagonist (K(i) = 200 nM and IC(50) = 2080 nM). In vivo, Lu AA21004 occupies the r5-HT(1B) receptor and rSERT (ED(50) = 3.2 and 0.4 mg/kg, respectively) after subcutaneous administration and is a 5-HT(3) receptor antagonist in the Bezold-Jarisch reflex assay (ED(50) = 0.11 mg/kg s.c.). In rat microdialysis experiments, Lu AA21004 (2.5-10.0 mg/kg s.c.) increased extracellular 5-HT, dopamine, and noradrenaline in the medial prefrontal cortex and ventral hippocampus. Lu AA21004 (5 mg/kg per day for 3 days; minipump subcutaneously), corresponding to 41% rSERT occupancy, significantly increased extracellular 5-HT in the ventral hippocampus. Furthermore, the 5-HT(3) receptor antagonist, ondansetron, potentiated the increase in extracellular levels of 5-HT induced by citalopram. Lu AA21004 has antidepressant- and anxiolytic-like effects in the rat forced swim (Flinders Sensitive Line) and social interaction and conditioned fear tests (minimal effective doses: 7.8, 2.0, and 3.9 mg/kg). In conclusion, Lu AA21004 mediates its pharmacological effects via two pharmacological modalities: SERT inhibition and 5-HT receptor modulation. In vivo, this results in enhanced release of several neurotransmitters and antidepressant- and anxiolytic-like profiles at doses for which targets in addition to the SERT are occupied. The multimodal activity profile of Lu AA21004 is distinct from that of current antidepressants.
Context
In pregnancy, vitamin D insufficiency and deficiency, defined as serum 25‐hydroxyvitamin D (25(OH)D) <50 nM, and <25 nM, respectively, may have adverse effects for both mother and child. ...Prevalence estimates, and identification of subgroups at special risk, may be useful for the planning of preventive strategies.
Objective
To study the prevalence and risk factors of hypovitaminosis D in early pregnancy.
Design and Methods
In a cross‐sectional study of 1348 women in early pregnancy from the Odense Child Cohort, Denmark, 25(OH)D was determined and correlated to demographic and lifestyle variables (age, nationality, skin tone, parity, prepregnancy body mass index (BMI), smoking and sun exposure), using multiple linear and logistic regression analyses for all year, or stratified for summer and winter. The risk of vitamin D insufficiency was expressed as odds ratios (OR) with 95% confidence intervals in brackets.
Results
The prevalence of vitamin D insufficiency and deficiency was estimated to 27·8% and 3·5% respectively. In adjusted analyses, vitamin D insufficiency was directly associated with winter season, OR = 1·89 (1·35–2·63); increasing prepregnancy BMI, OR = 1·06 (1·03–1·10); and smoking, OR = 2·7 (1·34–5·41); but was less frequent in nulliparous, OR = 0·47 (0·33–0·68) and tanned Caucasians, OR = 0·63 (0·41–0·97). Season‐specific associations having parental origin from outside Europe in summer, OR = 4·13 (1·41–12·13); in winter smoking, OR = 3·15 (1·19–8·36); and prepregnancy BMI, OR = 1·12 (1·06–1·18).
Conclusions
Vitamin D insufficiency was widespread in early pregnancy. Associations to smoking, prepregnancy BMI and origin outside Europe varied with season. Multiparity and not being tanned in Caucasians represent new risk factors of vitamin D insufficiency.
Plasmin is by far the predominant and most completely studied endogenous protease in bovine milk. Plasmin-induced proteolysis can have either beneficial or detrimental effects on the texture and ...flavor of dairy products, depending on the extent of hydrolysis and type of dairy product. In cheese, the breakdown of protein can help develop desirable flavors and texture during ripening, whereas in pasteurized milk and ultra-high-temperature milk, proteolysis causes undesirable gelation. Plasmin is part of a complex protease–protease inhibitor system in milk that consists of active and inactive forms of the enzyme, activators, and inhibitors. Considerable research has been done to isolate and characterize components of the plasmin system, determine how they interact, develop and compare quantitation methods, and determine how they are affected by cow characteristics, processing conditions, other milk components, storage conditions, and bacterial proteases. Considerable research has focused on enhancing or minimizing the activity of plasmin system components. The intent has been to control protease activity in casein and whey fractions, depending on the final food or ingredient application. Controlling the activity of plasmin has a great potential to improve dairy product quality and reduce their processing costs.
Edgewise vibrations with low aerodynamic damping are of particular concern in modern multi-megawatt wind turbines, as large amplitude cyclic oscillations may significantly shorten the life-time of ...wind turbine components, and even lead to structural damages or failures. In this paper, a new blade design with active controllers is proposed for controlling edgewise vibrations. The control is based on a pair of actuators/active tendons mounted inside each blade, allowing a variable control force to be applied in the edgewise direction. The control forces are appropriately manipulated according to a prescribed control law. A mathematical model of the wind turbine equipped with active controllers has been formulated using an Euler–Lagrangian approach. The model describes the dynamics of edgewise vibrations considering the aerodynamic properties of the blade, variable mass and stiffness per unit length and taking into account the effect of centrifugal stiffening, gravity and the interaction between the blades and the tower. Aerodynamic loads corresponding to a combination of steady wind including the wind shear and the effect of turbulence are computed by applying the modified Blade Element Momentum (BEM) theory. Multi-Blade Coordinate (MBC) transformation is applied to an edgewise reduced order model, leading to a linear time-invariant (LTI) representation of the dynamic model. The LTI description obtained is used for the design of the active control algorithm. Linear Quadratic (LQ) regulator designed for the MBC transformed system is compared with the control synthesis performed directly on an assumed nominal representation of the time-varying system. The LQ regulator is also compared against vibration control performance using Direct Velocity Feedback (DVF). Numerical simulations have been carried out using data from a 5-MW three-bladed Horizontal-Axis Wind Turbine (HAWT) model in order to study the effectiveness of the proposed active controlled blade design in reducing edgewise vibrations. Results show that the use of the proposed control scheme significantly improves the response of the blade and promising performances can be achieved. Furthermore, under the conditions considered in this study quantitative comparisons of the LQ-based control strategies reveal that there is a marginal improvement in the performances obtained by applying the MBC transformation on the time-varying edgewise vibration model of the wind turbine.
► Active controller design to suppress edgewise vibrations in wind turbine blades proposed. ► Control is based on actuators/active tendons mounted inside blades. ► Multi-modal model includes centrifugal stiffening, gravity effects and aerodynamic loading. ► Multi-blade coordinate transformation applied to the time-varying edgewise model. ► Linear quadratic regulator designed and different control strategies compared.
Tetracyclines are among the most used antibiotics in livestock worldwide. Resistance is widely disseminated in Escherichia coli, where it is generally mediated by tetracycline efflux pumps, such as ...TetA. Expression of tetracycline efflux pumps is tightly controlled by the repressor TetR, which has been shown to be tetracycline-responsive at sub-MIC tetracycline concentrations. The objective of this study was to investigate the effects of increasing tetracycline concentrations on the growth of TetA-producing E. coli, and to determine how expression of tetA and tetR related to each other in different growth phases in the presence of tetracycline.
A tetracycline resistant E. coli strain containing tetA and tetR on the chromosome was constructed and cultured in the presence of increasing concentrations of tetracycline. Expression of tetR and tetA was measured at four time points in different growth phases by quantitative real-time PCR. The TetA-producing E. coli exhibited prolonged lag phase with increasing concentrations of tetracycline, while expression of tetA and tetR increased and decreased, respectively, with increasing tetracycline concentration. The levels of tetA and tetR mRNA varied depending on growth phase, resulting in a gradual decrease of the tetA/tetR ratio from approximately 4 in the lag phase to approximately 2 in the stationary phase.
This study shows that the expression of tetR and tetA is tetracycline concentration- and growth phase-dependent, contributing to improved understanding of the relationships between E. coli growth, tetracycline exposure and expression of tetracycline resistance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
► Dynamic interaction between wind turbine structure and foundation system analyzed. ► MDOF model using Euler–Lagrangian approach developed. ► Aerodynamic effect and turbulence incorporated in the ...wind load. ► Impedance functions used for coupling the foundation to the structure. ► Foundation responses affected by blade rotation and soil-structure interaction.
This paper investigates the along-wind forced vibration response of an onshore wind turbine. The study includes the dynamic interaction effects between the foundation and the underlying soil, as softer soils can influence the dynamic response of wind turbines. A Multi-Degree-of-Freedom (MDOF) horizontal axes onshore wind turbine model is developed for dynamic analysis using an Euler–Lagrangian approach. The model is comprised of a rotor blade system, a nacelle and a flexible tower connected to a foundation system using a substructuring approach. The rotor blade system consists of three rotating blades and includes the effect of centrifugal stiffening due to rotation. The foundation of the structure is modeled as a rigid gravity based foundation with two DOF whose movement is related to the surrounding soil by means of complex impedance functions generated using cone model. Transfer functions for displacement of the turbine system are obtained and the modal frequencies of the combined turbine-foundation system are estimated. Simulations are presented for the MDOF turbine structure subjected to wind loading for different soil stiffness conditions. Steady state and turbulent wind loading, developed using blade element momentum theory and the Kaimal spectrum, have been considered. Soil stiffness and damping properties acquired from DNV/Risø standards are used as a comparison. The soil-structure interaction is shown to affect the response of the wind turbine. This is examined in terms of the turbine structural displacement and also the base shear and bending moment in the tower and the foundation. The frequency domain response of the bending moment and shear force in the foundation and the tower base, for stiffer soil condition, is shown to be characterized by peaks at multiples of the wind turbine rotational speed (3P effects). The effect of dynamic soil-structure interaction on the rotation of the foundation has also been investigated.
Summary
Background
Human skin is populated by diverse bacteria and there is increasing evidence that resident bacteria play a key role initiating immune responses in cutaneous diseases such as atopic ...dermatitis, psoriasis and hidradenitis suppurativa. Bacteria are present at all layers of the skin but many studies have relied on swabs to profile the skin microbiota.
Objectives
As the pathogenesis of many skin conditions is dermal, we wanted to compare the microbiota obtained in swabs (surface) and biopsies (dermis).
Methods
Using 16S rRNA gene sequencing we established the microbial profiles of skin swabs and skin biopsies in 16 patients.
Results
We found differences in both diversity and taxonomic composition of the microbiome obtained from swabs and biopsies of the same individual. Several taxa were found to be more abundant in the swabs, which displayed significantly higher community richness, but Clostridiales and Bacteroidetes were significantly enriched in the biopsies. Most published research on cutaneous microbiota has been based on skin swabs, which represent the surface of the skin.
Conclusions
Our study demonstrated a clear difference between the microbiome observed from skin swabs and skin biopsies. These findings may be highly relevant in disorders such as psoriasis where pathogenesis arises in the dermis.
What's already known about this topic?
16S RNA gene sequencing has facilitated study of the skin microbiome.
Several studies have sequenced the microbiome sampled by skin swabs.
What does this study add?
The microbiome data obtained using swabs and biopsies were different.
Diseases that are predominantly dermal should be studied using both swabs and biopsies.
Linked Comment: Bernigaud and Chosidow. Br J Dermatol 2019; 181:444–445.
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