Pharmacokinetics and safety of repirinast tablets in healthy Chinese subjects

Repirinast is a new, synthetic, disodium cromoglycate-like antiallergic agent for oral administration in humans. This study evaluated the safety, tolerability and pharmacokinetics of repirinast tablets in healthy Chinese volunteers. This was a phase I, open-label, randomized, single- and multiple-dose study. Subjects were assigned to receive a single dose of repirinast tablet at either 150, 300, or 450 mg, or multiple doses of 150 mg twice daily for 5 days. Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters of active metabolite MY-1250 (deesterified repirinast) were calculated using non-compartmental analysis with WinNonlin software. Statistical analysis was performed using SPSS software. All adverse events (AEs) were mild and of limited duration. No serious adverse event (SAE), death or withdrawal from the study was observed. In the single-dose study, Cmax was reached at about 0.75 hour, and the mean t1/2 was approximately 16.21 hours. Area under curve (AUC) and Cmax increased with dose escalation, but dose proportionality was not observed over the range of 150 to 450 mg. In the multiple-dose study, the steady-state was reached within 3 days with no accumulation. Repirinast tablet was well tolerated in healthy Chinese subjects

Hybrid intelligent deep kernel incremental extreme learning machine based on differential evolution and multiple population grey wolf optimization methods

Focussing on the problem that redundant nodes in the kernel incremental extreme learning machine (KI-ELM) which leads to ineffective iteration increase and reduce the learning efficiency, a novel improved hybrid intelligent deep kernel incremental extreme learning machine (HI-DKIELM) based on a hybrid intelligent algorithms and kernel incremental extreme learning machine is proposed. At first, hybrid intelligent algorithms are proposed based on differential evolution (DE) and multiple population grey wolf optimization (MPGWO) methods which used to optimize the hidden layer neuron parameters and then to determine the effective hidden layer neurons number. The learning efficiency of the algorithm is improved by reducing the network complexity. Then, we bring in the deep network structure to the kernel incremental extreme learning machine to extract the original input data layer by layer gradually. The experiment results show that the HI-DKIELM methods proposed in this paper with more compact network structure have higher prediction accuracy and better ability of generation compared with other ELM methods

Storage of multiple single-photon pulses emitted from a quantum dot in a solid-state quantum memory

Quantum repeaters are critical components for distributing entanglement over long distances in presence of unavoidable optical losses during transmission. Stimulated by Duan-Lukin-Cirac-Zoller protocol, many improved quantum-repeater protocols based on quantum memories have been proposed, which commonly focus on the entanglement-distribution rate. Among these protocols, the elimination of multi-photons (multi-photon-pairs) and the use of multimode quantum memory are demonstrated to have the ability to greatly improve the entanglement-distribution rate. Here, we demonstrate the storage of deterministic single photons emitted from a quantum dot in a polarization-maintaining solid-state quantum memory; in addition, multi-temporal-mode memory with $1$, $20$ and $100$ narrow single-photon pulses is also demonstrated. Multi-photons are eliminated, and only one photon at most is contained in each pulse. Moreover, the solid-state properties of both sub-systems make this configuration more stable and easier to be scalable. Our work will be helpful in the construction of efficient quantum repeaters based on all-solid-state devicesComment: Published version, including supplementary materia

Laser Direct Writing of Visible Spin Defects in Hexagonal Boron Nitride for Applications in Spin-Based Technologies

Optically addressable spins in two-dimensional hexagonal boron nitride (hBN) attract widespread attention for their potential advantage in on-chip quantum devices, such as quantum sensors and quantum network. A variety of spin defects have been found in hBN, but no convenient and deterministic generation methods have been reported for other defects except negatively charged boron vacancy ($V_B^-$). Here we report that by using femtosecond laser direct writing technology, we can deterministically create spin defect ensembles with spectra range from 550 nm to 800 nm on nanoscale hBN flakes. Positive single-peak optically detected magnetic resonance (ODMR) signals are detected in the presence of magnetic field perpendicular to the substrate, and the contrast can reach 0.8%. With the appropriate thickness of hBN flakes, substrate and femtosecond laser pulse energy, we can deterministically and efficiently generate bright spin defect array. Our results provide a convenient deterministic method to create spin defects in hBN, which will motivate more endeavors for future researches and applications of spin-based technologies such as quantum magnetometer array

Molecular subtypes predict the preferential site of distant metastasis in advanced breast cancer: a nationwide retrospective study

ObjectiveThis study aimed to explore possible associations between molecular subtypes and site of distant metastasis in advanced breast cancer (ABC).Methods3577 ABC patients were selected from 21 hospitals of seven geographic regions in China from 2012-2014. A questionnaire was designed to collect medical information regarding demographic characteristics, risk factors, molecular subtype, recurrence/metastasis information, and disease-free survival (DFS). The cancers were classified into Luminal A, Luminal B, HER2-enriched and Triple Negative subtypes. Chi-square test and multivariate Cox proportional hazard models were performed to explore the associations between molecular subtypes and distant metastasis sites.ResultsA total of 2393 cases with molecular subtypes information were finally examined. Patients with Luminal A (51.1%) and Luminal B (44.7%) were most prone to bone metastasis, whereas liver metastasis was more frequently observed in HER2-enriched ABC patients (29.1%).The cumulative recurrence and metastasis rates of ABC patients at 36 months of DFS were the most significant within molecular types, of which Triple Negative was the highest (82.7%), while that of Luminal A was the lowest (58.4%). In the adjusted Cox regression analysis, Luminal B, HER2-enriched and Triple Negative subtypes increased the risk of visceral metastasis by 23%, 46% and 87% respectively. In addition, Triple Negative patients had a higher probability of brain metastasis (HR 3.07, 95% CI: 1.04-9.07).ConclusionMolecular subtypes can predict the preferential sites of distant metastasis, emphasizing that these associations were of great help in choices for surveillance, developing appropriate screening and cancer management strategies for follow-up and personalized therapy in ABC patients

Corrigendum to: The TianQin project: current progress on science and technology

In the originally published version, this manuscript included an error related to indicating the corresponding author within the author list. This has now been corrected online to reflect the fact that author Jun Luo is the corresponding author of the article

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

The effect of food intake on the pk of rhein released from diacerein

Diacerein is a symptomatic slow-acting drug used for treating osteoarthritis. This drug is completely metabolized into the active metabolite rhein before reaching the systemic circulation. This study evaluated the effects of food on the pharmacokinetics of rhein released from diacerein in healthy Chinese subjects. This was a single-center, randomized, single-dose, open-label, two-period, cross-over study. Twentyfour healthy subjects were randomly selected to receive a single oral dose of 50 mg diacerein capsule in either fasted or fed state on two separate visits. Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters were calculated using WinNonlin software. In the fasted and fed states, the main pharmacokinetic parameters of diacerein capsule were as follows: Cmax were (4471 ± 936), (3225 ± 755) ng/mL, t1/2 were (4.22 ± 0.42), (4.19 ± 1.05) h, tmax were (2.61 ± 1.25), (3.81 ± 1.29) h, AUC0-24 h were (24223 ± 4895), (24316 ± 5856) h·ng/mL, and AUC0-∞ were (24743 ± 5046), (25170 ± 6415) h·ng/mL. The absorption rate of diacerein capsule was obviously delayed by food intake but the absorption degree remained unaffected