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There is a continuous demand to improve monoclonal antibody production for medication supply and medical cost reduction. For over 20 years, recombinant Chinese hamster ovary cells have been used as a host in monoclonal antibody production due to robustness, high productivity and ability to produce proteins with ideal glycans. Chemical compounds, such as dimethyl sulfoxide, lithium chloride, and butyric acid, have been shown to improve monoclonal antibody production in mammalian cell cultures. In this study, we aimed to discover new chemical compounds that can improve cell-specific antibody production in recombinant Chinese hamster ovary cells. Out of the 23,227 chemicals screened in this study, 4-(2,5-dimethyl-1H-pyrrol-1-yl)-N-(2,5-dioxopyrrolidin-1-yl) benzamide was found to increase monoclonal antibody production. The compound suppressed cell growth and increased both cell-specific glucose uptake rate and the amount of intracellular adenosine triphosphate during monoclonal antibody production. In addition, the compound also suppressed the galactosylation on a monoclonal antibody, which is a critical quality attribute of therapeutic monoclonal antibodies. Therefore, the compound might also be used to control the level of the galactosylation for the N-linked glycans. Further, the structure-activity relationship study revealed that 2,5-dimethylpyrrole was the most effective partial structure of 4-(2,5-dimethyl-1H-pyrrol-1-yl)-N-(2,5-dioxopyrrolidin-1-yl) benzamide on monoclonal antibody production. Further structural optimization of 2,5-dimethylpyrrole derivatives could lead to improved production and quality control of monoclonal antibodies.

Two-way Euler-Lagrange simulations are performed to characterize the hydrodynamics in the single-use bioreactor Mobius® CellReady 3 L. The hydrodynamics in stirred tank bioreactors are frequently modeled with the Euler–Euler approach, which cannot capture the trajectories of single bubbles. The present study employs the two-way coupled Euler–Lagrange approach, which accounts for the individual bubble trajectories through Langrangian equations and considers their impact on the Eulerian liquid phase equations. Hydrodynamic process characteristics that are relevant for cell cultivation including the oxygen mass transfer coefficient, the mixing time, and the hydrodynamic stress are evaluated for different working volumes, sparger types, impeller speeds, and sparging rates. A microporous sparger and an open pipe sparger are considered where bubbles of different sizes are generated, which has a pronounced impact on the bubble dispersion and the volumetric oxygen mass transfer coefficient. It is found that only the microporous sparger provides sufficiently high oxygen transfer to support typical suspended mammalian cell lines. The simulated mixing time and the volumetric oxygen mass transfer coefficient are successfully validated with experimental results. Due to the small reactor size, mixing times are below 25 s across all tested conditions. For the highest sparging rate of 100 mL min−1, the mixing time is found to be two seconds shorter than for a sparging rate of 50 mL min−1, which again, is 0.1 s longer than for a sparging rate of 10 mL min−1 at the same impeller speed of 100 rpm and the working volume of 1.7 L. The hydrodynamic stress in this bioreactor is found to be below critical levels for all investigated impeller speeds of up to 150 rpm, where the maximum levels are found in the region where the bubbles pass behind the impeller blades.

Understanding the hydrodynamic conditions in bioreactors is of utmost importance for the selection of operating conditions during cell culture process development. In the present study, the two-phase flow in the lab-scale single-use bioreactor XcellerexTM XDR-10 is characterized for working volumes from 4.5 L to 10 L, impeller speeds from 40 rpm to 360 rpm, and sparging with two different microporous spargers at rates from 0.02 L min−1 to 0.5 L min−1. The numerical simulations are performed with the one-way coupled Euler–Lagrange and the Euler–Euler models. The results of the agitated liquid height, the mixing time, and the volumetric oxygen mass transfer coefficient are compared to experiments. For the unbaffled XDR-10, strong surface vortex formation is found for the maximum impeller speed. To support the selection of suitable impeller speeds for cell cultivation, the surface vortex formation, the average turbulence energy dissipation rate, the hydrodynamic stress, and the mixing time are analyzed and discussed. Surface vortex formation is observed for the maximum impeller speed. Mixing times are below 30 s across all conditions, and volumetric oxygen mass transfer coefficients of up to 22.1 h−1 are found. The XDR-10 provides hydrodynamic conditions which are well suited for the cultivation of animal cells, despite the unusual design of a single bottom-mounted impeller and an unbaffled cultivation bioreactor.

Purpose: The radiation recall phenomenon (RRP) is a rare and unexpected late complication of radiation therapy (RT). Although predominantly in the skin, RRP of the upper respiratory tract has also been reported. In general, RRP is caused by anticancer agents, and the COVID-19 vaccine has also been reported to cause RRP in recent years. Methods and Materials: A 50-year-old woman who had received RT around the larynx 3 years prior and was receiving a docetaxel + ramucirumab (RAM) regimen experienced recurrent sore throat. The administration of RAM was discontinued after a gastroscopic examination revealed mucosal bleeding from around the larynx, which was thought to be RRP caused by RAM, a vascular endothelial growth factor inhibitor. Results: After the remission of the RRP, the patient received a COVID-19 vaccine (Pfizer-BioNTech). Five days later, the appearance of cough and recurrence of sore throat worsened with time, and marked stridor was observed. The patient was admitted, and steroid pulse therapy was administered for 3 days starting on day 18 after vaccination. On day 50 after vaccination, edema of the vocal cords improved. Conclusions: When administering COVID-19 vaccines, considering that these vaccines may cause RRP is important, because RRP can be fatal in patients with a history of RT in the laryngeal region and treated with vascular endothelial growth factor inhibitors.

Abstract This field survey was conducted during summer in actual bedrooms and used polysomnography to evaluate the effect of thermal environment on sleep quality by analyzing electroencephalogram, electro‐oculogram, and electromyogram signals, which were continuously measured during sleep. It was found that the effect of the thermal environment (ie, air temperature, air velocity, and air turbulence) on sleep quality varied according to the sleep cycle and stages. The effect of air turbulence depended mainly on the air temperature. At low or neutral temperatures, air turbulence had negative effects on sleep quality, whereas under warm temperatures, air turbulence had negligible effects on sleep quality.

The photocatalytic decomposition of ethylene in a spiral-type reactor was investigated to develop a method for preserving the quality of agricultural products. Ethylene was injected or discharged from an apple into a 0.016 m3 closed container and was photocatalytically decomposed in the reactor at 25 °C. The results indicated that ethylene was decomposed and became undetectable (the amount of ethylene was lower than the detection limit of 40 ppb), which is useful for preserving the quality of agricultural products over long periods of time. For the demonstration experiment, we placed an apple, a persimmon, a cucumber, a cabos (Citrus sphaerocarpa), and a banana in a 0.117 m3 closed container at 25 °C. When the air inside the container was not photocatalytically treated, the concentration of ethylene increased up to 2.7 ppm. This lowered the quality of the persimmon, cucumber, and apple significantly. In contrast, when the air inside the container was photocatalytically treated, they remained fresh for at least nine days. Methane was simultaneously generated as a byproduct. It was hypothesized that methane was the product of the photocatalytic decomposition of some unknown chemical compound released from the analyzed agricultural products; however, we were unable to identify the chemical compound. Computer simulations using experimentally determined parameter values suggested that the decomposition of ethylene begins before or as soon as agricultural products are stored in closed rooms, such as truck containers. In conclusion, the photocatalytic decomposition of ethylene using a spiral-type reactor is effective for preserving the quality of agricultural products.

Abstract Purpose The HyperArc VMAT (HA-VMAT) planning approach was newly developed to fulfill the demands of dose delivery for brain metastases stereotactic radiosurgery. We compared the dosimetric parameters of the HA-VMAT plan with those of the conventional VMAT (C-VMAT). Material and methods For 23 patients (1–4 brain metastases), C-VMAT and HA-VMAT plans with a prescription dose of 20–24 Gy were retrospectively generated, and dosimetric parameters for PTV (homogeneity index, HI; conformity index, CI; gradient index, GI) and brain tissue (V2Gy-V16Gy) were evaluated. Subsequently, the physical characteristics (modulation complexity score for VMAT, MCSV; Monitor unit, MU) of both treatment approaches were compared. Results HA-VMAT provided higher HI (1.41 ± 0.07 vs. 1.24 ± 0.07, p