Investigation of morphological changes in the tamsui river estuary using an integrated coastal and estuarine processes model

© 2020 by the authors. This study is to investigate morphological changes in the Tamsui River Estuary in Taiwan driven by multiple physical processes, such as river flows, tides, waves, and storm surges, and then to study the impacts of sediment flushing operated at the Shihmen reservoir upstream on the river estuary. An integrated coastal and estuarine processes model (CCHE2D-Coast) (Center for Computational Hydroscience and Engineering Two-Dimensional-Coast) was validated by simulating these physical processes in the estuary driven by three historical typhoons in 2008. The site-specifically validated model was then applied to simulate morphological changes in the estuary in response to reservoir sediment flush scenarios from the upstream. For the impact assessment of sediment flushing, a synthetic hydrological event was designed by including a historical typhoon and a typical monsoon. It was found that during the typhoon, the sediments will be mostly deposited in the estuarine river reach of Tamsui and the Wazihwei sandy beach. During the monsoon period, most of the sediments tend to be deposited in the second fishing port of Tamsui, the northern breakwater, and the estuary, while the Wazihwei sandy beach in the river mouth would be scoured by backflow. Simulations of the complex flow fields and morphological changes will facilitate the best practice of sediment management in the coastal and estuarine regions

Decay Constants of Pseudoscalar DD-mesons in Lattice QCD with Domain-Wall Fermion

We present the first study of the masses and decay constants of the pseudoscalar $D$ mesons in two flavors lattice QCD with domain-wall fermion. The gauge ensembles are generated on the $24^3 \times 48$ lattice with the extent $N_s = 16$ in the fifth dimension, and the plaquette gauge action at $\beta = 6.10$, for three sea-quark masses with corresponding pion masses in the range $260-475$ MeV. We compute the point-to-point quark propagators, and measure the time-correlation functions of the pseudoscalar and vector mesons. The inverse lattice spacing is determined by the Wilson flow, while the strange and the charm quark masses by the masses of the vector mesons $\phi(1020)$ and $J/\psi(3097)$ respectively. Using heavy meson chiral perturbation theory (HMChPT) to extrapolate to the physical pion mass, we obtain $f_D = 202.3(2.2)(2.6)$ MeV and $f_{D_s} = 258.7(1.1)(2.9)$ MeV.Comment: 15 pages, 3 figures. v2: the statistics of ensemble (A) with m_sea = 0.005 has been increased, more details on the systematic error, to appear in Phys. Lett.

Matrix Metalloproteinase-8 Mediates the Unfavorable Systemic Impact of Local Irradiation on Pharmacokinetics of Anti-Cancer Drug 5-Fluorouracil

Concurrent chemoradiation with 5-fluorouracil (5-FU) is widely accepted for cancer treatment. However, the interactions between radiation and 5-FU remain unclear. Here, we evaluated the influence of local irradiation on the pharmacokinetics of 5-FU in rats. The single-fraction radiation was delivered to the whole pelvic fields of Sprague-Dawley rats after computerized tomography-based planning. 5-FU at 100 mg/kg was prescribed 24 hours after radiation. A high-performance liquid chromatography system was used to measure 5-FU in the blood. Matrix metalloproteinase-8 (MMP-8) inhibitor I was administered to examine whether or not RT modulation of 5-FU pharmacokinetic parameters could be blocked. Compared with sham-irradiated controls, whole pelvic irradiation reduced the area under the concentration versus time curve (AUC) of 5-FU in plasma and, in contrast, increased in bile with a radiation dose-dependent manner. Based on protein array analysis, the amount of plasma MMP-8 was increased by whole pelvic irradiation (2.8-fold by 0.5 Gy and 5.3-fold by 2 Gy) in comparison with controls. Pretreatment with MMP-8 inhibitor reversed the effect of irradiation on AUC of 5-FU in plasma. Our findings first indicate that local irradiation modulate the systemic pharmacokinetics of 5-FU through stimulating the release of MMP-8. The pharmacokinetics of 5-FU during concurrent chemoradiaiton therapy should be rechecked and the optimal 5-FU dose should be reevaluated, and adjusted if necessary, during CCRT

Pilot Scale Production of Highly Efficacious and Stable Enterovirus 71 Vaccine Candidates

BACKGROUND: Enterovirus 71 (EV71) has caused several epidemics of hand, foot and mouth diseases (HFMD) in Asia and now is being recognized as an important neurotropic virus. Effective medications and prophylactic vaccine against EV71 infection are urgently needed. Based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated EV71 vaccine candidate has been developed and currently in human phase 1 clinical trial. PRINCIPAL FINDING: In this report, we present the development of a serum-free cell-based EV71 vaccine. The optimization at each step of the manufacturing process was investigated, characterized and quantified. In the up-stream process development, different commercially available cell culture media either containing serum or serum-free was screened for cell growth and virus yield using the roller-bottle technology. VP-SFM serum-free medium was selected based on the Vero cell growth profile and EV71 virus production. After the up-stream processes (virus harvest, diafiltration and concentration), a combination of gel-filtration liquid chromatography and/or sucrose-gradient ultracentrifugation down-stream purification processes were investigated at a pilot scale of 40 liters each. Although the combination of chromatography and sucrose-gradient ultracentrifugation produced extremely pure EV71 infectious virus particles, the overall yield of vaccine was 7-10% as determined by a VP2-based quantitative ELISA. Using chromatography as the downstream purification, the virus yield was 30-43%. To retain the integrity of virus neutralization epitopes and the stability of the vaccine product, the best virus inactivation was found to be 0.025% formalin-treatment at 37 °C for 3 to 6 days. Furthermore, the formalin-inactivated virion vaccine candidate was found to be stable for >18 months at 4 °C and a microgram of viral proteins formulated with alum adjuvant could induce strong virus-neutralizing antibody responses in mice, rats, rabbits, and non-human primates. CONCLUSION: These results provide valuable information supporting the current cell-based serum-free EV71 vaccine candidate going into human Phase I clinical trials