Soft X-ray resonant Kerr rotation measurement and simulation of element-resolved and interface-sensitive magnetization reversals in a NiFe/FeMn/Co trilayer structure

We report experimental observations of element- and buried interface-resolved magnetization reversals in an oppositely exchange-biased NiFeFeMnCo trilayer structure by soft x-ray resonant Kerr rotation measurements. Not only Co-, Ni-, Fe-specific exchange-biased loops but also interfacial uncompensated (UC) Fe reversal loops coupled to the individual Co and NiFe layers are separately observed. From the experimental results interpreted with the help of the model simulations of soft x-ray resonant Kerr rotation, the effective thicknesses of interfacial UC regions at the buried interfaces of both FeMnCo and NiFeFeMn are found to be tUC =13??2 A and 6??4 A, respectively. The depth sensitivity as well as element specificity of the x-ray resonant Kerr effect offer an elegant way into the investigations of element- and depth-resolved magnetization reversals of ferromagnetic ultrathin regions at buried interfaces in multicomponent multilayer films.open91

Hydrogenation-induced atomic stripes on the 2H-MoS2 surface

We report that the hydrogenation of a single crystal 2H-MoS2 induces a novel-intermediate phase between 2H and 1T phases on its surface, i.e., the large-area, uniform, robust, and surface array of atomic stripes through the intralayer atomic-plane gliding. The total energy calculations confirm that the hydrogenation-induced atomic stripes are energetically most stable on the MoS2 surface between the semiconducting 2H and metallic 1T phase. Furthermore, the electronic states associated with the hydrogen ions, which is bonded to sulfur anions on both sides of the MoS2 surface layer, appear in the vicinity of the Fermi level (E-F) and reduces the band gap. This is promising in developing the monolayer-based field-effect transistor or vanishing the Schottky barrier for practical applicationsopen

Population pharmacokinetics of artesunate and dihydroartemisinin following single- and multiple-dosing of oral artesunate in healthy subjects

<p>Abstract</p> <p>Background</p> <p>The population pharmacokinetics of artesunate (AS) and its active metabolite dihydroartemisinin (DHA) were studied in healthy subjects receiving single- or multiple-dosing of AS orally either in combination with pyronaridine (PYR) or as a monotherapy with or without food.</p> <p>Methods</p> <p>Data from 118 concentration-time profiles arising from 91 healthy Korean subjects were pooled from four Phase I clinical studies. Subjects received 2-5 mg/kg of single- and multiple-dosing of oral AS either in combination with PYR or as a monotherapy with or without food. Plasma AS and DHA were measured simultaneously using a validated liquid chromatography- mass spectrometric method with a lower limit of quantification of 1 ng/mL for both AS and DHA. Nonlinear mixed-effect modelling was used to obtain the pharmacokinetic and variability (inter-individual and residual variability) parameter estimates.</p> <p>Results</p> <p>A novel parent-metabolite pharmacokinetic model consisting of a dosing compartment, a central compartment for AS, a central compartment and a peripheral compartment for DHA was developed. AS and DHA data were modelled simultaneously assuming stoichiometric conversion to DHA. AS was rapidly absorbed with a population estimate of absorption rate constant (Ka) of 3.85 h^-1. The population estimates of apparent clearance (CL/F) and volume of distribution (V2/F) for AS were 1190 L/h with 36.2% inter-individual variability (IIV) and 1210 L with 57.4% IIV, respectively. For DHA, the population estimates of apparent clearance (CLM/F) and central volume of distribution (V3/F) were 93.7 L/h with 28% IIV and 97.1 L with 30% IIV, respectively. The population estimates of apparent inter-compartmental clearance (Q/F) and peripheral volume of distribution (V4/F) for DHA were 5.74 L/h and 18.5 L, respectively. Intake of high-fat and high-caloric meal prior to the drug administration resulted in 84% reduction in Ka. Body weight impacted CLM/F, such that a unit change in weight resulted in 1.9-unit change in CLM/F in the same direction.</p> <p>Conclusions</p> <p>A novel simultaneous parent-metabolite pharmacokinetic model with good predictive power was developed to study the population pharmacokinetics of AS and DHA in healthy subjects following single- and multiple-dosing of AS with or without the presence of food. Food intake and weight were significant covariates for Ka and CLM/F, respectively.</p

A minimally invasive lens-free computational microendoscope

Ultra-miniaturized microendoscopes are vital for numerous biomedical applications. Such minimally invasive imagers allow for navigation into hard-to-reach regions and observation of deep brain activity in freely moving animals. Conventional solutions use distal microlenses. However, as lenses become smaller and less invasive, they develop greater aberrations and restricted fields of view. In addition, most of the imagers capable of variable focusing require mechanical actuation of the lens, increasing the distal complexity and weight. Here, we demonstrate a distal lens-free approach to microendoscopy enabled by computational image recovery. Our approach is entirely actuation free and uses a single pseudorandom spatial mask at the distal end of a multicore fiber. Experimentally, this lensless approach increases the space-bandwidth product, i.e., field of view divided by resolution, by threefold over a best-case lens-based system. In addition, the microendoscope demonstrates color resolved imaging and refocusing to 11 distinct depth planes from a single camera frame without any actuated parts.R21 EY028436 - NEI NIH HHS; R21 EY028381 - NEI NIH HHSPublished versio

Resting-State Glucose Metabolism Level Is Associated with the Regional Pattern of Amyloid Pathology in Alzheimer's Disease

It has been suggested that glucose metabolism within the brain's default network is directly associated with—and may even cause—the amyloid pathology of Alzheimer's disease (AD). Here we performed 2-[18F]fluoro-2-deoxy-D-glucose (FDG) and [11C]-labeled Pittsburgh Compound B (PIB) positron emission tomography (PET) on cognitively normal elderly subjects and on AD patients and conducted quantitative regional analysis of FDG- and PIB-PET images using an automated region of interest technique. We confirmed that resting glucose metabolism within the posterior components of the brain's default network is high in normal elderly subjects and low in AD patients, which is partially in agreement with the regional pattern of PIB uptake within the default network of AD patients. However, in several regions outside the default network, glucose metabolism was high in normal elderly subjects but was not depressed in AD patients, who exhibited significantly increased PIB uptakes in these regions. In contrast, the level of resting glucose metabolism in the default network and in regions outside the default network in normal elderly subjects was significantly correlated with the level of regional PIB uptake in AD patients. These results are discussed with experimental evidence suggesting that beta amyloid production and amyloid precursor protein regulation are dependent on neuronal activity

real world efficacy and safety of nebivolol in korean patients with hypertension from the benefit korea study

Objective:The efficacy and safety of nebivolol in patients with hypertension is well established, but its effect in Asian patients with essential hypertension in the real world has not been studied.Methods:Adult South Korean patients with essential hypertension, with or without comorbidities, were

Symmetry energy of dense matter in holographic QCD

We study the nuclear symmetry energy of dense matter using holographic QCD. To this end, we consider two flavor branes with equal quark masses in a D4/D6/D6 model. We find that at all densities the symmetry energy monotonically increases. At small densities, it exhibits a power law behavior with the density, $E_{\rm sym} \sim \rho^{1/2}$.Comment: 9 pages, 3 figure

Automatic segmentation of multiple cardiovascular structures from cardiac computed tomography angiography images using deep learning.

OBJECTIVES:To develop, demonstrate and evaluate an automated deep learning method for multiple cardiovascular structure segmentation. BACKGROUND:Segmentation of cardiovascular images is resource-intensive. We design an automated deep learning method for the segmentation of multiple structures from Coronary Computed Tomography Angiography (CCTA) images. METHODS:Images from a multicenter registry of patients that underwent clinically-indicated CCTA were used. The proximal ascending and descending aorta (PAA, DA), superior and inferior vena cavae (SVC, IVC), pulmonary artery (PA), coronary sinus (CS), right ventricular wall (RVW) and left atrial wall (LAW) were annotated as ground truth. The U-net-derived deep learning model was trained, validated and tested in a 70:20:10 split. RESULTS:The dataset comprised 206 patients, with 5.130 billion pixels. Mean age was 59.9 ± 9.4 yrs., and was 42.7% female. An overall median Dice score of 0.820 (0.782, 0.843) was achieved. Median Dice scores for PAA, DA, SVC, IVC, PA, CS, RVW and LAW were 0.969 (0.979, 0.988), 0.953 (0.955, 0.983), 0.937 (0.934, 0.965), 0.903 (0.897, 0.948), 0.775 (0.724, 0.925), 0.720 (0.642, 0.809), 0.685 (0.631, 0.761) and 0.625 (0.596, 0.749) respectively. Apart from the CS, there were no significant differences in performance between sexes or age groups. CONCLUSIONS:An automated deep learning model demonstrated segmentation of multiple cardiovascular structures from CCTA images with reasonable overall accuracy when evaluated on a pixel level

Transient upregulation of postsynaptic IP3-gated Ca release underlies short-term potentiation of metabotropic glutamate receptor 1 signaling in cerebellar Purkinje cells

Synaptic plasticity lasting approximately 100 s has been suggested to function as a temporary buffer for neural information. One example of this was reported by Batchelor and Garthwaite (1997), who found that a slow metabotropic glutamate receptor 1 (mGluR1)-evoked EPSP produced by burst stimulation of cerebellar parallel fiber-Purkinje cell synapses could be potentiated by a conditioning stimulus consisting of prior activation of climbing fiber synapses (or injection of depolarizing current) with a delay of up to 90 s. What is the molecular basis of the signal that spans this temporal gap? Here, we show that mGluR1-evoked slow EPSCs evoked by parallel fiber burst test stimuli show a similar form of short-term potentiation (mGluR1-STP) and that this phenomenon is also observed when parallel fiber bursts are replaced by pressure pulses of an exogenous mGluR1 agonist. Ca imaging experiments revealed that cytosolic Ca levels returned to baseline within several seconds after conditioning depolarization, indicating that this cannot underlie mGluR1-STP. To test the hypothesis that transient upregulation of inositol-1,4,5-trisphosphate (IP(3))-gated Ca release underlies this phenomenon, we used local photolytic uncaging of IP(3) to deplete IP(3)-gated Ca stores. IP(3) uncaging in the interval between conditioning depolarization and the test pulse produced a complete blockade of mGluR1-STP, as did blockade of IP(3) receptors with heparin. When Ca transients evoked by IP(3) uncaging were used as a test stimulus, conditioning depolarization produced a large STP of Ca response amplitudes. These data suggest that transient upregulation of postsynaptic IP(3)-gated Ca signaling constitutes a novel form of short-term synaptic plasticity