The preparation, characterization, and pharmacokinetic studies of chitosan nanoparticles loaded with paclitaxel/dimethyl-β-cyclodextrin inclusion complexes.

A novel biocompatible and biodegradable drug-delivery nanoparticle (NP) has been developed to minimize the severe side effects of the poorly water-soluble anticancer drug paclitaxel (PTX) for clinical use. PTX was loaded into the hydrophobic cavity of a hydrophilic cyclodextrin derivative, heptakis (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD), using an aqueous solution-stirring method followed by lyophilization. The resulting PTX/DM-β-CD inclusion complex dramatically enhanced the solubility of PTX in water and was directly incorporated into chitosan (CS) to form NPs (with a size of 323.9–407.8 nm in diameter) using an ionic gelation method. The formed NPs had a zeta potential of +15.9–23.3 mV and showed high colloidal stability. With the same weight ratio of PTX to CS of 0.7, the loading efficiency of the PTX/DM-β-CD inclusion complex-loaded CS NPs was 30.3-fold higher than that of the PTX-loaded CS NPs. Moreover, it is notable that PTX was released from the DM-β-CD/CS NPs in a sustained-release manner. The pharmacokinetic studies revealed that, compared with reference formulation (Taxol(®)), the PTX/DM-β-CD inclusion complex-loaded CS NPs exhibited a significant increase in AUC(0→24h) (the area under the plasma drug concentration–time curve over the period of 24 hours) and mean residence time by 2.7-fold and 1.4-fold, respectively. Therefore, the novel drug/DM-β-CD inclusion complex-loaded CS NPs have promising applications for the significantly improved delivery and controlled release of the poorly water-soluble drug PTX or its derivatives, thus possibly leading to enhanced therapeutic efficacy and less severe side effects

Full em Design Method for HTS MMIC Josephson Mixers

© 2002-2011 IEEE. We report the full electromagnetic (EM) design and simulation method, and applied it to develop a 34-GHz high-temperature superconducting (HTS) microwave monolithic integrated circuit Josephson mixer. The mixer is modeled in EM simulation software, high-frequency simulation structural simulator, with the junction area modeled as an excitation port with frequency-dependent impedance. Impedance matching between the junction and RF/IF ports is then optimized accordingly. Module design is carried out for the optimized HTS Josephson mixer, and the cavity resonance issue is investigated and eliminated. The HTS mixer module was experimentally developed and measured to verify the simulation. The measured frequency response of the conversion gain agrees with the simulation results of combined RF and IF transmission loss

0.34-THz High-Temperature Superconducting Josephson-Junction Mixer with Superior Noise and Conversion Performance

© 2018 IEEE. We present, in this work, a new thin-film antenna-coupled high-temperature superconducting (HTS) Josephson-junction terahertz (THz) mixer that demonstrates superior performance at frequencies around 0.34 THz. A novel dual-meander-slot thin-film antenna is designed to significantly improve the antenna-junction impedance matching and thus more efficient coupling of the THz signal power. Theoretical and experimental investigations are carried out to evaluate the mixer performance. This mixer can be applied to the sensitive THz wireless receivers

HTS step-edge Josephson junction terahertz harmonic mixer

© 2016 Federal Australian Crown copyright. A high-temperature superconducting (HTS) terahertz (THz) frequency down-converter or mixer based on a thin-film ring-slot antenna coupled YBa2Cu3O7-x (YBCO)/MgO step-edge Josephson junction is reported. The frequency down-conversion was achieved using higher order harmonics of an applied lower frequency (19-40 GHz) local oscillator signal in the Josephson junction mixing with a THz signal of over 600 GHz, producing a 1-3 GHz intermediate frequency signal. Up to 31st order of harmonic mixing was obtained and the mixer operated stably at temperatures up to 77 K. The design details of the antenna, HTS Josephson junction mixer, the matching and isolation circuits, and the DC and RF performance evaluation are described in this paper

A 36 GHz HTS MMIC Josephson mixer - Simulation and measurement

© 2002-2011 IEEE. Modeling, simulation, and measurement of a compact 36 GHz high-temperature superconducting (HTS) monolithic Josephson junction mixer are presented in this paper. A full HTS microwave monolithic integrated circuit (MMIC) simulation was carried out for the circuit combining HTS passive devices and the Josephson junction. Optimal impedance matching and bias conditions were investigated, and the circuit layout was designed accordingly. The HTS circuit has a compact dimension of 5 × 4 × 0.3 mm3, including filters, resonators, and impedance matching circuits. The HTS MMIC mixer was fabricated and packaged with an LNA to realize a receiver front end with a total dimension of 28 × 25 × 15 mm3. Measurement result showed an overall conversion gain around 35 dB, with local oscillator driving power around -45 dBm at operating temperature of 40 K

Harmonic Mixing Using a HTS Step-Edge Josephson Junction at 0.6 THz Frequency

© 2002-2011 IEEE. A high-temperature superconducting (HTS) terahertz (THz) heterodyne mixer based on a thin-film antenna-coupled YBa 2Cu3O7-x step-edge Josephson junction is presented. The frequency down-conversion from 0.6 THz to an intermediate frequency (IF) of 2 GHz was achieved using high-order harmonic mixing of a local oscillator (LO), thus removing the need to use a second THz source as the LO pumping source. The DC and RF characteristics of the harmonic mixer as well as the relationship of the IF output power versus the harmonic number were experimentally studied and compared with simulated results. Most of our measurements were made at 40 K, but we also observed stable harmonic mixing at 77 K which we believe has not been reported previously in HTS junction mixers

Extent of Safety Database in Pediatric Drug Development: Types of Assessment, Analytical Precision, and Pathway for Extrapolation through On-Target Effects

Pediatric patients should have access to medicines that have been appropriately evaluated for safety and efficacy. Given this goal of revised labelling, the adequacy of the pediatric clinical development plan and resulting safety database must inform a favorable benefit-risk assessment for the intended use of the medicinal product. While extrapolation from adults can be used to support efficacy of drugs in children, there may be a reluctance to use the same approach in safety assessments, wiping out potential gains in trial efficiency through a reduction of sample size. To address this reluctance, we explore safety review in pediatric trials, including factors affecting these data, specific types of safety assessments, and precision on the estimation of event rates for specific adverse events (AEs) that can be achieved. In addition, we discuss the assessments which can provide a benchmark for the use of extrapolation of safety that focuses on on-target effects. Finally, we explore a unified approach for understanding precision using Bayesian approaches as the most appropriate methodology to describe/ascertain risk in probabilistic terms for the estimate of the event rate of specific AEs

Assessing impacts of climate change and human activities on streamflow and sediment discharge in the Ganjiang River basin (1964-2013)

© 2019 by the authors. National large-scale soil and water conservation controls on the Gangjiang River basin have been documented, but the effect of governance on regional watershed hydrology and how the main driving factors act have not been systematically studied yet. To do this, this study evaluated changing trends and detected transition years for both streamflow and sediment discharge using long-term historical records at seven hydrological stations in the Ganjiang River basin over the past 50 years. The double mass curve (DMC) method was used to quantify the effects of both climate change and human activities on hydrological regime shifts. The results showed that the distributions of precipitation, streamflow, and sediment discharge within a year are extremely uneven and mainly concentrated in the flood season of Jiangxi Province. None of the stations showed significant trends over time for either annual precipitation or streamflow, while the annual sediment discharge at most stations decreased significantly over time. The estimation of sediment discharge via DMC indicated that after the transition years, there were rapid reductions in sediment discharge at all hydrological stations, and the average decline degree of midstream and downstream were much larger than that of upstream. Human activities, especially the increase of vegetation cover and construction of large and medium-sized reservoirs, provided a significantly greater contribution to the reduction of sediment discharge than did precipitation changes. As a case study of river evolution under global change environment, this study could provide scientific basis for the control of soil erosion and the management of water resources in Ganjiang River, as well as for the related research of Poyang Lake and the Yangtze River basin of China