Defisit anggaran, utang pemerintah dan keberlanjutan fiscal: aplikasi model vector error correction
Notice bibliographique
Résumé
<i>p</i>-Tyramine (TYR) is an endogenous trace amine, which can also be synthesized by intestinal microbiota, and is present in commonly consumed diets. TYR is an agonist for the intracellular trace amine-associated receptor 1, which has been implicated in psychiatric, metabolic, and immune-related disorders. We have previously demonstrated TYR readily diffuses across lipid bilayers, while transport across Caco-2 cell membranes involves Organic Cation Transporter 2 (OCT2) and a Na<sup>+</sup>-dependent active transporter. Here we developed mathematical models to determine whether known kinetics for these processes are sufficient to explain observed transcellular TYR passage. Ordinary differential equations were developed for known TYR transport processes to predict concentration-time relationships. Michaelis-Menten kinetics were assumed for all transporter-mediated processes and a one phase exponential function used for simple diffusion. Modelled concentration-time plots were compared to published experimental results. Additional transporter functions were sequentially added to models to improve consistency, and a least squares error minimization approach utilized to determine added transporter kinetics. Finally, possible TYR compartmentalization was also modelled. Following apical loading, transport across the apical, but not the basolateral, membrane was modelled without additional transporters, suggesting a basolateral transporter was missing. Consistent with this, models of basolateral compartment loading did not match experimental observations, indicating missing basolateral transporters were bidirectional. Addition of a transporter with the kinetic characteristics of OCT2 did not improve models. Varying the kinetic parameters of the added transporter improved models of basolateral, but worsened apical, loading models, suggesting the need for either a directional preference in transporters, or intracellular TYR compartmentalization. Experimental parameters were recapitulated by introducing asymmetry into the apical OCT2 (K<sub>t_OCT2_apicaltocell</sub> = 110.4 nM, K<sub>t_OCT2_celltoapical</sub> = 1,227.9 nM), and a symmetric basolateral facilitated diffusion transporter (V<sub>max</sub> = 6.0 nM/s, K<sub>t</sub> = 628.3 nM). The apparent directionality of OCT2 may reflect altered TYR ionization due to known pH differences between compartments. Models for asymmetry and compartmentalization were compared by root mean square deviation from experimental data, and it was found that TYR compartmentalization could only partially replace the need for asymmetry of OCT2. In conclusion, modelling indicates that known TYR transport processes are insufficient to explain experimental concentration-time profiles and that asymmetry of the apical membrane OCT2 combined with additional, low affinity, basolateral membrane facilitated diffusion transporters are required.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».