Enhanced cell growth, production, and mAb quality produced in Chinese hamster ovary-K1 cells by supplementing polyamine in the media.

Polyamines such as putrescine (PUT), spermidine (SPD), and spermine (SPM) are amine group-containing biomolecules that regulate multiple intracellular functions such as proliferation, differentiation, and stress response in mammalian cells. Although these biomolecules can be generated intracellularly, lack of polyamine-synthesizing activity has occasionally been reported in a few mammalian cell lines such as Chinese hamster ovary (CHO)-K1; thus, polyamine supplementation in serum-free media is required to support cell growth and production. In the present study, the effects of biogenic polyamines PUT, SPD, and SPM in media on cell growth, production, metabolism, and antibody quality were explored in cultures of antibody-producing CHO-K1 cells. Polyamine withdrawal from media significantly suppressed cell growth and production. On the other hand, enhanced culture performance was achieved in polyamine-containing media conditions in a dose-dependent manner regardless of polyamine type. In addition, in polyamine-deprived medium, distinguishing metabolic features, such as enriched glycolysis and suppressed amino acid consumption, were observed and accompanied by higher heterogeneity of antibody quality compared with the optimal concentration of polyamines. Furthermore, an excessive concentration of polyamines negatively affected culture performance as well as antibody quality. Hence, the results suggest that polyamine-related metabolism needs to be further investigated and polyamines in cell growth media should be optimized as a controllable parameter in CHO cell culture bioprocessing. KEY POINTS: • Polyamine supplementation enhanced cell growth and production in a dose-dependent manner • Polyamine type and concentration in the media affected mAb quality • Optimizing polyamines in the media is suggested in CHO cell bioprocessing.

Flexible Acceptance Condition of Generics from a Probabilistic Viewpoint: Towards Formalization of the Semantics of Generics.

Formalization of the semantics of generics has been considered extremely challenging for their inherent vagueness and context-dependence that hinder a single fixed truth condition. The present study suggests a way to formalize the semantics of generics by constructing flexible acceptance conditions with comparative probabilities. Findings from our in-depth psycholinguistic experiment show that two comparative probabilities-cue validity and prevalence-indeed construct the flexible acceptance conditions for generics in a systematic manner that can be applied to a diverse types of generics: Acceptability of IS_A relational generics is mostly determined by prevalence without interaction with cue validity; feature-describing generics are endorsed acceptable with high cue validity, albeit mediated by prevalence; and acceptability of feature-describing generics with low cue validity is mostly determined by prevalence irrespective of cue validity. Such systematic patterns indicate a great potential for the formalization of the semantics of generics.

Control of basic fibroblast growth factor release from fibrin gel with heparin and concentrations of fibrinogen and thrombin.

Basic fibroblast growth factor (bFGF) has been known to stimulate the regeneration of a number of tissues including cartilage, nerve, skin, liver, and blood vessel. Delivery of bFGF for a long period in a controlled manner would enhance stimulative effects. The purpose of the present study is to test the hypothesis that the kinetics of bFGF release from fibrin gels could be controlled with heparin and concentrations of fibrinogen and thrombin. The kinetics of bFGF release from fibrin gels with various concentrations of fibrinogen, thrombin, and heparin was determined. The bioactivity of bFGF released from fibrin gels was assessed using dermal fibroblast cell culture. To examine the therapeutic potential of the bFGF delivery system, bFGF-loaded fibrin gels were injected into mouse ischemic limbs. The addition of heparin to fibrin gels decreased the bFGF release rate. As the thrombin content in fibrin gels increased, the bFGF release rate significantly decreased. Similarly, increased concentration of fibrinogen in fibrin gels decreased the bFGF release rate. Basic FGF released from fibrin gels exhibited significantly higher extents of fibroblast growth than bFGF added in a free form daily into the culture medium, suggesting that the fibrin gels may stabilize the bFGF bioactivity. Immunohistological analysis of mouse ischemic limbs indicated that the microvessel density was much higher in the ischemic limbs treated with injection of bFGF-loaded fibrin gels than in the ischemic limbs with no treatment. This study showed that the rate of bFGF release from fibrin gels can be controlled and that the bFGF delivery system has therapeutic potentials for angiogenesis.

Humanoid Path Planning From HRI Perspective: A Scalable Approach via Waypoints With a Time Index.

This paper proposes a path planner for a humanoid robot to enhance its performance in terms of the human-robot interaction perspective. From the human point of view, the proposed method uses the time index that can generate a path that humans feel to be natural. In terms of the robot, the proposed method yields a waypoint-based path, the simplicity of which enables accurate tracking even for humanoid robots with complex dynamics. From an environmental perspective through which interactions occur, the proposed method can be easily expanded to a wide area. Overall, the proposed method can be described as a scalable path planner via waypoints with a time index for humanoid robots. Experiments have been conducted in test beds where the robot encounters unexpected exceptional situations. Throughout these trials, the robot successfully reached the goal location while iteratively replanning the path.