Pharmacokinetic Evaluation of Clozapine in Concomitant Use of Radix Rehmanniae, Fructus Schisandrae, Radix Bupleuri, or Fructus Gardeniae in Rats

Abstract: Radix Rehmanniae, Fructus Schisandrae, Radix Bupleuri, and Fructus Gardeniae are often used alongside with clozapine (CLZ) for schizophrenia patients in order to reduce side effects and enhance therapeutic efficacy. However, worse outcomes were observed raising concern about a critical issue, herb-drug interactions, which were rarely reported when antipsychotics were included. This study aims to determine whether the concomitant use of these herbal medicines affects the pharmacokinetic characteristics of CLZ in rat models. Rats were given a single or multiple intraperitoneal injections of 10 mg/kg CLZ, either alone or with individual herbal water extracts administered orally. CLZ and its two inactive metabolites, norclozapine and clozapine N-oxide, were determined by high-performance liquid chromatography/tandem mass spectrometry. In the acute treatment, the formation of both metabolites was reduced, while no significant change was observed in the CLZ pharmacokinetics for any of the herbal extracts. In the chronic treatment, none of the four herbal extracts significantly influenced the pharmacokinetic parameters of CLZ and its metabolites. Renal and liver functions stayed normal after the 11-day combined use of herbal medicines. Overall, the four herbs had limited interaction effect on CLZ pharmacokinetics in the acute and chronic treatment. Herb-drug interaction includes both pharmacokinetic and pharmacodynamic mechanisms. This result gives us a hint that pharmacodynamic herb-drug interaction, instead of pharmacokinetic types, may exist and need further confirmation.published_or_final_versio

Big data analytics for large-scale wireless networks: Challenges and opportunities

© 2019 Association for Computing Machinery. The wide proliferation of various wireless communication systems and wireless devices has led to the arrival of big data era in large-scale wireless networks. Big data of large-scale wireless networks has the key features of wide variety, high volume, real-time velocity, and huge value leading to the unique research challenges that are different from existing computing systems. In this article, we present a survey of the state-of-art big data analytics (BDA) approaches for large-scale wireless networks. In particular, we categorize the life cycle of BDA into four consecutive stages: Data Acquisition, Data Preprocessing, Data Storage, and Data Analytics. We then present a detailed survey of the technical solutions to the challenges in BDA for large-scale wireless networks according to each stage in the life cycle of BDA. Moreover, we discuss the open research issues and outline the future directions in this promising area

SCTSC: A Semicentralized Traffic Signal Control Mode With Attribute-Based Blockchain in IoVs

This is the author accepted manuscript. The final version is available from IEEE via the DOI in this recordAssisting traffic control is one of the most important applications on the Internet of Vehicles (IoVs). Traffic information provided by vehicles is desired since drivers or vehicle sensors are sensitive in perceiving or detecting nuances on roads. However, the availability and privacy preservation of this information are critical while conflicted with each other in the vehicular communication. In this paper, we propose a semicentralized mode with attribute-based blockchain in IoVs to balance the tradeoff between the availability and the privacy preservation. In this mode, a method of control-by-vehicles is used to control signals of traffic lights to increase traffic efficiency. Users are grouped their attributes such as locations and directions before starting the communication. The users reach an agreement on determining a temporary signal timing by interacting with each other without leaking privacy. Final decisions are verifiable to all users, even if they have no a priori agreement and processes of consensus. The mode not only achieves the aim of privacy preservation but also supports responsibility investigation for historical agreements via ciphertext-policy attribute-based encryption (CP-ABE) and blockchain technology. Extensive experimental results demonstrated that our mode is efficient and practical.National Key R&D Program of ChinaNatural Science Foundation of ChinaFundamental Research Funds for the Central Universities of Chin

Design and Aerodynamic Investigation of Dynamic Architecture

The effect of the spacing between adjacent building floors on the wind distribution and turbulence intensity was analysed using computational fluid dynamics in this study. Five computational models were created with floor spacing ranging from 0.8 m (benchmark) to 1.6 m. The three-dimensional Reynolds-Averaged Navier–Stokes equations along with the momentum and continuity equations were solved using the FLUENT code for obtaining the velocity and pressure field. Simulating a reference wind speed of 5.5 m/s, the findings from the study quantified that at a floor spacing of 1.6 m, the overall wind speed augmentation was 39 % which was much higher than the benchmark model (floor spacing = 0.8 m) indicating an amplification in wind speed of approximately 27 %. In addition, the results indicated a gradual reduction in turbulence kinetic energy by up to 53 % when the floor spacing was increased from 0.8 to 1.6 m. Although the concept was to integrate wind turbines into the building fabric, this study is limited to the assessment of the airflow inside the spaces of building floors which can be potentially harnessed by a vertical axis wind turbine. The findings of this work have indicated that there is a potential for integration which will lead on to future research in this area

Immunotherapy for neuroblastoma using syngeneic fibroblasts transfected with IL-2 and IL-12

Cytokine-modified tumour cells have been used in clinical trials for immunotherapy of neuroblastoma, but primary tumour cells from surgical biopsies are difficult to culture. Autologous fibroblasts, however, are straightforward to manipulate in culture and easy to transfect using nonviral or viral vectors. Here we have compared the antitumour effect of fibroblasts and tumour cells transfected ex vivo to coexpress interleukin-2 (IL-2) and IL-12 in a syngeneic mouse model of neuroblastoma. Coinjection of cytokine-modified fibroblasts with Neuro-2A tumour cells abolished their in vivo tumorigenicity. Treatment of established tumours with three intratumoral doses of transfected fibroblasts showed a significant therapeutic effect with reduced growth or complete eradication of tumours in 90% of mice, associated with extensive leukocyte infiltration. Splenocytes recovered from vaccinated mice showed enhanced IL-2 production following Neuro-2A coculture, and increased cytotoxicity against Neuro-2A targets compared with controls. Furthermore, 100% of the tumour-free mice exhibited immune memory against tumour cells when rechallenged three months later. The potency of transfected fibroblasts was equivalent to that of tumour cells in all experiments. We conclude that syngeneic fibroblasts cotransfected with IL-2 and IL-12 mediate therapeutic effects against established disease, and are capable of generating immunological memory. Furthermore, as they are easier to recover and manipulate than autologous tumour cells, fibroblasts provide an attractive alternative immunotherapeutic strategy for the treatment of neuroblastoma

Sunscreens - Which and what for?

It is well established that sun exposure is the main cause for the development of skin cancer. Chronic continuous UV radiation is believed to induce malignant melanoma, whereas intermittent high-dose UV exposure contributes to the occurrence of actinic keratosis as precursor lesions of squamous cell carcinoma as well as basal cell carcinoma. Not only photocarcinogenesis but also the mechanisms of photoaging have recently become apparent. In this respect the use of sunscreens seemed to prove to be more and more important and popular within the last decades. However, there is still inconsistency about the usefulness of sunscreens. Several studies show that inadequate use and incomplete UV spectrum efficacy may compromise protection more than previously expected. The sunscreen market is crowded by numerous products. Inorganic sunscreens such as zinc oxide and titanium oxide have a wide spectral range of activity compared to most of the organic sunscreen products. It is not uncommon for organic sunscreens to cause photocontact allergy, but their cosmetic acceptability is still superior to the one given by inorganic sunscreens. Recently, modern galenic approaches such as micronization and encapsulation allow the development of high-quality inorganic sunscreens. The potential systemic toxicity of organic sunscreens has lately primarily been discussed controversially in public, and several studies show contradictory results. Although a matter of debate, at present the sun protection factor (SPF) is the most reliable information for the consumer as a measure of sunscreen filter efficacy. In this context additional tests have been introduced for the evaluation of not only the protective effect against erythema but also protection against UV-induced immunological and mutational effects. Recently, combinations of UV filters with agents active in DNA repair have been introduced in order to improve photoprotection. This article reviews the efficacy of sunscreens in the prevention of epithelial and nonepithelial skin cancer, the effect on immunosuppression and the value of the SPF as well as new developments on the sunscreen market. Copyright (C) 2005 S. Karger AG, Basel

Dual-gated bilayer graphene hot electron bolometer

Detection of infrared light is central to diverse applications in security, medicine, astronomy, materials science, and biology. Often different materials and detection mechanisms are employed to optimize performance in different spectral ranges. Graphene is a unique material with strong, nearly frequency-independent light-matter interaction from far infrared to ultraviolet, with potential for broadband photonics applications. Moreover, graphene's small electron-phonon coupling suggests that hot-electron effects may be exploited at relatively high temperatures for fast and highly sensitive detectors in which light energy heats only the small-specific-heat electronic system. Here we demonstrate such a hot-electron bolometer using bilayer graphene that is dual-gated to create a tunable bandgap and electron-temperature-dependent conductivity. The measured large electron-phonon heat resistance is in good agreement with theoretical estimates in magnitude and temperature dependence, and enables our graphene bolometer operating at a temperature of 5 K to have a low noise equivalent power (33 fW/Hz1/2). We employ a pump-probe technique to directly measure the intrinsic speed of our device, >1 GHz at 10 K.Comment: 5 figure

A novel isolator-based system promotes viability of human embryos during laboratory processing

In vitro fertilisation (IVF) and related technologies are arguably the most challenging of all cell culture applications. The starting material is a single cell from which one aims to produce an embryo capable of establishing a pregnancy eventually leading to a live birth. Laboratory processing during IVF treatment requires open manipulations of gametes and embryos, which typically involves exposure to ambient conditions. To reduce the risk of cellular stress, we have developed a totally enclosed system of interlinked isolator-based workstations designed to maintain oocytes and embryos in a physiological environment throughout the IVF process. Comparison of clinical and laboratory data before and after the introduction of the new system revealed that significantly more embryos developed to the blastocyst stage in the enclosed isolator-based system compared with conventional open-fronted laminar flow hoods. Moreover, blastocysts produced in the isolator-based system contained significantly more cells and their development was accelerated. Consistent with this, the introduction of the enclosed system was accompanied by a significant increase in the clinical pregnancy rate and in the proportion of embryos implanting following transfer to the uterus. The data indicate that protection from ambient conditions promotes improved development of human embryos. Importantly, we found that it was entirely feasible to conduct all IVF-related procedures in the isolator-based workstations

A closed-loop EKF and multi-failure diagnosis approach for cooperative GNSS positioning

Current cooperative positioning with Global Navigation Satellite System (GNSS) for connected vehicle application mainly uses pseudorange measurements. However the positioning accuracy offered cannot meet the requirements for lane-level positioning, collision avoidance and future automatic driving, which needs real-time positioning accuracy of better than 0.5m. Furthermore, there is an apparent lack of research into the integrity issue for these new applications under emerging driverless vehicle applications. In order to overcome those problems, a new Extended Kalman Filter (EKF) and a multi-failure diagnosis algorithm are developed to process both GNSS pseudorange and carrier phase measurements. We first introduce a new closed-loop EKF with partial ambiguity resolution (PAR) as feedback to address the low accuracy issue. Then a multi-failure diagnosis algorithm is proposed to improve integrity and reliability. The core of this new algorithm includes using Carrier phase based Receiver Autonomous Integrity Monitoring (CRAIM) method for failure detection, and the double extended w-test detectors to identify failure. A cooperative positioning experiment was carried out to validate the proposed method. The results show that the proposed closed-loop EKF can provide highly accurate positioning, and the multi-failure diagnosis method is effective in detecting and identifying failures for both code and carrier phase measurements