RESUMO
The complete automation of materials manufacturing with high productivity is a key problem in some materials processing. In floating zone (FZ) crystal growth, which is a manufacturing process for semiconductor wafers such as silicon, an operator adaptively controls the input parameters in accordance with the state of the crystal growth process. Since the operation dynamics of FZ crystal growth are complicated, automation is often difficult, and usually the process is manually controlled. Here we demonstrate automated control of FZ crystal growth by reinforcement learning using the dynamics predicted by Gaussian mixture modeling (GMM) from small numbers of trajectories. Our proposed method of constructing the control model is completely data-driven. Using an emulator program for FZ crystal growth, we show that the control model constructed by our proposed model can more accurately follow the ideal growth trajectory than demonstration trajectories created by human operation. Furthermore, we reveal that policy optimization near the demonstration trajectories realizes accurate control following the ideal trajectory.
RESUMO
SCOPE: The gastrointestinal (GI) tract senses and responds to intraluminal nutrients and these interactions often affect GI functions. We found that, among basic amino acids, l-ornithine (Orn) and l-lysine (Lys) stimulated but l-arginine (Arg) suppressed GI motility after oral administration (24 mmol/kg) in mice (Orn and Lys, 14.3 and 26.4% promotion; Arg, 7.7% suppression). We investigated the mechanism of the action of Orn and Lys on GI motility. METHODS AND RESULTS: Orn-induced promotion of small intestinal transit was significantly inhibited (p<0.05) by oral administration of capsazepine, a transient receptor potential vanilloid 1 (TRPV1) antagonist. Moreover, the stimulatory effect of Orn and Lys was abolished in TRPV1-knockout mice. In TRPV1-transfected HEK293 cells, Orn and Lys (10 mM) evoked Ca2+ influx, which was blocked by ruthenium red, a TRP channel antagonist. These results suggest that Orn and Lys promote GI motility via activation of TRPV1. The GI motility stimulation by Orn and Lys was also blocked by atropine, a muscarinic acetylcholine receptor (mAChR) antagonist, or NG -nitro-l-arginine methyl ester, a nitric oxide (NO) synthase inhibitor. CONCLUSION: Orally administered Orn and Lys stimulate GI motility via TRPV1, mAChR and NO synthase in mice.
Assuntos
Sinalização do Cálcio , Motilidade Gastrointestinal , Lisina/administração & dosagem , Ornitina/administração & dosagem , Canais de Cátion TRPV/agonistas , Regulação para Cima , Animais , Arginina/administração & dosagem , Arginina/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Regulação para Baixo/efeitos dos fármacos , Motilidade Gastrointestinal/efeitos dos fármacos , Células HEK293 , Humanos , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/fisiologia , Lisina/metabolismo , Masculino , Moduladores de Transporte de Membrana/farmacologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Mutantes , Ornitina/metabolismo , Ratos , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Rutênio Vermelho/farmacologia , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
SCOPE: Recently, we found that dipeptide Arg-Phe (RF) had cholecystokinin (CCK)-dependent vasorelaxing activity. The RF sequence is often observed in the primary structure of natural food proteins. In the current study, we investigated enzymatic conditions for the release of RF-related peptides from rice glutelin, a major storage protein, using gastrointestinal proteases. RF-related peptides were then characterized. METHODS AND RESULTS: It was found that RF and Ile-His-Arg-Phe (IHRF) were released in the chymotrypsin digest of the partial structure of rice glutelin. We then focused on previously unidentified IHRF, corresponding to rice glutelin(155-158). IHRF had vasorelaxing activity in the mesenteric artery of spontaneous hypertensive rats (SHRs). Orally administered IHRF lowered systolic blood pressure in SHRs. The antihypertensive activity of IHRF was more potent and long-lasting than that of RF. IHRF-induced vasorelaxing activity was not blocked by inhibitors of nitric oxide synthase and cyclooxygenase, but by an antagonist for CCK1 receptor. IHRF also had CCK-like suppressive activities in food intake and gastrointestinal transit. IHRF increased intracellular Ca²âº flux and CCK release in the enteroendocrine cell STC-1. CONCLUSION: IHRF, a novel CCK-dependent vasorelaxing peptide, decreases both blood pressure and food intake in rodents.