The mammalian outer hair cell (OHC) protein prestin (Slc26a5) differs from other Slc26 family members due to its unique piezoelectric-like property that drives OHC electromotility, the putative ...mechanism for cochlear amplification. Here, we use cryo-electron microscopy to determine prestin's structure at 3.6 Å resolution. Prestin is structurally similar to the anion transporter Slc26a9. It is captured in an inward-open state which may reflect prestin's contracted state. Two well-separated transmembrane (TM) domains and two cytoplasmic sulfate transporter and anti-sigma factor antagonist (STAS) domains form a swapped dimer. The transmembrane domains consist of 14 transmembrane segments organized in two 7+7 inverted repeats, an architecture first observed in the bacterial symporter UraA. Mutation of prestin's chloride binding site removes salicylate competition with anions while retaining the prestin characteristic displacement currents (Nonlinear Capacitance), undermining the extrinsic voltage sensor hypothesis for prestin function.
A previous genetic study has suggested that schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) share common ...disease-associated genes. However, whether individuals with first-degree relatives (FDRs) with schizophrenia have a higher risk of these major psychiatric disorders requires further investigation. This study used Taiwan's National Health Insurance Research Database and identified 151 650 patients with schizophrenia and 227 967 individuals with FDRs with schizophrenia. The relative risks (RRs) of schizophrenia and other major psychiatric disorders were assessed in individuals with FDRs with schizophrenia. The individuals with FDRs with schizophrenia exhibited higher RRs (95% confidence interval) of major psychiatric disorders, namely schizophrenia (4.76, 4.65-4.88), bipolar disorder (3.23, 3.12-3.35), major depressive disorder (2.05, 2.00-2.10), ASD (2.55, 2.35-2.77) and ADHD (1.31, 1.25-1.37) than were found in the total population. Several sensitivity analyses were conducted to confirm these results. A dose-dependent relationship was observed between the risks of major psychiatric disorders and the numbers of FDRs with schizophrenia. The increased risks of major psychiatric disorders were consistent in different family relationships, namely among parents, offspring, siblings and twins. Our study supports the familial dose-dependent co-aggregation of schizophrenia, bipolar disorder, major depressive disorder, ASD and ADHD, and our results may prompt governmental public health departments and psychiatrists to focus on the mental health of individuals with FDRs with schizophrenia.
We interpret the Taylor–Green cellular vortex model in terms of the Kolmogorov length and velocity scales, in order to study the balance between aggregation and breakup of cohesive sediment in ...fine-scale turbulence. One-way coupled numerical simulations, which capture the effects of cohesive, lubrication and direct contact forces on the flocculation process, reproduce the non-monotonic relationship between the equilibrium floc size and shear rate observed in previous experiments. The one-way coupled results are confirmed by select two-way coupled simulations. Intermediate shear gives rise to the largest flocs, as it promotes preferential concentration of the primary particles without generating sufficiently strong turbulent stresses to break up the emerging aggregates. We find that the optimal intermediate shear rate increases for stronger cohesion and smaller particle-to-fluid density ratios, and we propose a simple model for the equilibrium floc size that agrees well with experimental data reported in the literature.
CdTe quantum dots show increased quantum yields when incorporated into a temperature‐sensitive poly(N‐isopropylacrylamide) hydrogel (see Figure). The fluorescence intensities and maximum emission ...wavelengths are sensitive to external temperature stimuli and are completely reversible.
The first searches for axions and axionlike particles with the Large Underground Xenon experiment are presented. Under the assumption of an axioelectric interaction in xenon, the coupling constant ...between axions and electrons g_{Ae} is tested using data collected in 2013 with an exposure totaling 95 live days ×118 kg. A double-sided, profile likelihood ratio statistic test excludes g_{Ae} larger than 3.5×10^{-12} (90% C.L.) for solar axions. Assuming the Dine-Fischler-Srednicki-Zhitnitsky theoretical description, the upper limit in coupling corresponds to an upper limit on axion mass of 0.12 eV/c^{2}, while for the Kim-Shifman-Vainshtein-Zhakharov description masses above 36.6 eV/c^{2} are excluded. For galactic axionlike particles, values of g_{Ae} larger than 4.2×10^{-13} are excluded for particle masses in the range 1-16 keV/c^{2}. These are the most stringent constraints to date for these interactions.
ABSTRACT We report the first detection of a gap and a ring in 336 GHz dust continuum emission from the protoplanetary disk around TW Hya, using the Atacama Large Millimeter/Submillimeter Array ...(ALMA). The gap and ring are located at around 25 and 41 au from the central star, respectively, and are associated with the CO snow line at ∼30 au. The gap has a radial width of less than 15 au and a mass deficit of more than 23%, taking into account that the observations are limited to an angular resolution of ∼15 au. In addition, the 13CO and C18O lines show a decrement in CO line emission throughout the disk, down to ∼10 au, indicating a freeze-out of gas-phase CO onto grain surfaces and possible subsequent surface reactions to form larger molecules. The observed gap could be caused by gravitational interaction between the disk gas and a planet with a mass less than super-Neptune (2 ), or could be the result of the destruction of large dust aggregates due to the sintering of CO ice.
Summary
Background
Dupilumab is an antibody against interleukin‐4 receptor α, used in the treatment of atopic dermatitis (AD).
Objectives
To evaluate the efficacy and safety of dupilumab in adult ...Chinese patients with moderate‐to‐severe AD.
Methods
In this randomized, double‐blind, placebo‐controlled, parallel‐group, phase III study, conducted between December 2018 and February 2020, patients with AD received dupilumab (300 mg) or placebo once every 2 weeks for 16 weeks, and were followed up for 12 weeks. The primary efficacy endpoint was the proportion of patients with both an Investigator’s Global Assessment score of 0–1 and a reduction from baseline of ≥ 2 points at week 16.
Results
Overall, 165 patients (mean age 30·6 years; 71·5% male patients) were randomized; 82 patients were randomized to dupilumab and 83 patients were randomized to placebo. At week 16, 26·8% of patients in the dupilumab group and 4·8% of patients in the placebo group achieved the primary endpoint difference 22·0%, 95% confidence interval (CI) 11·37–32·65; P < 0·001. Compared with placebo, higher proportions of patients in the dupilumab group achieved ≥ 75% reduction in the Eczema Area and Severity Index score (57·3% vs. 14·5%; difference 42·9%, 95% CI 29·75–55·97; P < 0·001) and had ≥ 3‐point (52·4% vs. 9·6%; difference 42·8%, 95% CI 30·26–55·34; P < 0·001) and ≥ 4‐point (39·0% vs. 4·8%; difference 34·2%, 95% CI 22·69–45·72; P < 0·001) reductions in weekly average daily peak daily pruritus numerical rating scale scores. The incidence of treatment‐emergent adverse events during the treatment period was similar in the two groups. The incidence of conjunctivitis, allergic conjunctivitis and injection site reaction was higher in the dupilumab group than in the placebo group.
Conclusions
In adult Chinese patients, dupilumab was effective in improving the signs and symptoms of AD and demonstrated a favourable safety profile.
What is already known about this topic?
Two randomized, placebo‐controlled phase III trials (SOLO 1 and SOLO 2) have demonstrated that dupilumab is effective and safe when used in the treatment of atopic dermatitis in adults.
However, very few Chinese participants were included and, therefore, the efficacy and safety of dupilumab in this population is unclear.
What does this study add?
The findings of this randomized, placebo‐controlled phase III trial show that dupilumab is effective in improving the signs and symptoms of atopic dermatitis in adult Chinese patients and has a favourable safety profile in this population.
Plain language summary available online
Abstract
We report the observations of periodic nulling in PSR B2111+46 at 1250 MHz with the Five-hundred-meter Aperture Spherical radio Telescope (FAST). The nulling fractions (NF) as well as ...nulling period of this pulsar were calculated. The NF and nulling period are 17% ± 1% and 62.49 ± 0.99
P
1
, respectively, and the periodic nulling shows variations in periodicity with time. The durations of each consecutive burst and nulling were investigated, which show that the power-law distribution and the indices are −1.11 ± 0.04 and −2.08 ± 0.23. In the observed frequency band, the width of the profile is narrowed with the increase in frequency, and the degree of polarization has no obvious trend with the increase in frequency. We discovered a weak emission component in front of the leading component of this triple-type profile pulsar that was not observed in other bands and by other telescopes. With the fitting of rotation vector model, we obtained that the angles of the magnetic inclination
α
and the line of sight
ζ
are ∼13.°0 and ∼11.°6, respectively. The high-sensitivity observation of FAST improves our understanding of the emission of this pulsar.
We investigate the dynamics of cohesive particles in homogeneous isotropic turbulence, based on one-way coupled simulations that include Stokes drag, lubrication, cohesive and direct contact forces. ...We observe a transient flocculation phase, followed by a statistically steady equilibrium phase. We analyse the temporal evolution of floc size and shape due to aggregation, breakage and deformation. Larger turbulent shear and weaker cohesive forces yield smaller elongated flocs. Flocculation proceeds most rapidly when the fluid and particle time scales are balanced and a suitably defined Stokes number is $O(1)$. During the transient stage, cohesive forces of intermediate strength produce flocs of the largest size, as they are strong enough to cause aggregation, but not so strong as to pull the floc into a compact shape. Small Stokes numbers and weak turbulence delay the onset of the equilibrium stage. During equilibrium, stronger cohesive forces yield flocs of larger size. The equilibrium floc size distribution exhibits a preferred size that depends on the cohesive number. We observe that flocs are generally elongated by turbulent stresses before breakage. Flocs of size close to the Kolmogorov length scale preferentially align themselves with the intermediate strain direction and the vorticity vector. Flocs of smaller size tend to align themselves with the extensional strain direction. More generally, flocs are aligned with the strongest Lagrangian stretching direction. The Kolmogorov scale is seen to limit floc growth. We propose a new flocculation model with a variable fractal dimension that predicts the temporal evolution of the floc size and shape.
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