Prediction of Blood-Brain Barrier Penetration (BBBP) Based on Molecular Descriptors of the Free-Form and In-Blood-Form Datasets

The blood-brain barrier (BBB) controls the entry of chemicals from the blood to the brain. Since brain drugs need to penetrate the BBB, rapid and reliable prediction of BBB penetration (BBBP) is helpful for drug development. In this study, free-form and in-blood-form datasets were prepared by modifying the original BBBP dataset, and the effects of the data modification were investigated. For each dataset, molecular descriptors were generated and used for BBBP prediction by machine learning (ML). For ML, the dataset was split into training, validation, and test data by the scaffold split algorithm MoleculeNet used. This creates an unbalanced split and makes the prediction difficult; however, we decided to use that algorithm to evaluate the predictive performance for unknown compounds dissimilar to existing ones. The highest prediction score was obtained by the random forest model using 212 descriptors from the free-form dataset, and this score was higher than the existing best score using the same split algorithm without using any external database. Furthermore, using a deep neural network, a comparable result was obtained with only 11 descriptors from the free-form dataset, and the resulting descriptors suggested the importance of recognizing the glucose-like characteristics in BBBP prediction.

Role of Oxytocin and Vasopressin in Neuropsychiatric Disorders: Therapeutic Potential of Agonists and Antagonists

Oxytocin (OT) and vasopressin (AVP) are hypothalamic neuropeptides classically associated with their regulatory role in reproduction, water homeostasis, and social behaviors. Interestingly, this role has expanded in recent years and has positioned these neuropeptides as therapeutic targets for various neuropsychiatric diseases such as autism, addiction, schizophrenia, depression, and anxiety disorders. Due to the chemical-physical characteristics of these neuropeptides including short half-life, poor blood-brain barrier penetration, promiscuity for AVP and OT receptors (AVP-R, OT-R), novel ligands have been developed in recent decades. This review summarizes the role of OT and AVP in neuropsychiatric conditions, as well as the findings of different OT-R and AVP-R agonists and antagonists, used both at the preclinical and clinical level. Furthermore, we discuss their possible therapeutic potential for central nervous system (CNS) disorders.

Influence of halo single-neutron transfer on near barrier $$^{15}$$C + $$^{12}$$C total fusion

A recent comparison of the average fusion cross section, $$\left\langle \sigma _\mathrm {F}\right\rangle $$ σ F , for energies just above the Coulomb barrier for the $$^{12-15}$$ 12 - 15 C + $$^{12}$$ 12 C systems found that the behaviour as a function of projectile neutron excess could not be satisfactorily explained by static barrier penetration model calculations and suggested that the neutron dynamics plays an important rôle. In this work we demonstrate that the ($$^{15}$$ 15 C,$$^{14}$$ 14 C) single neutron transfer has a significant influence on the above barrier $$^{15}$$ 15 C + $$^{12}$$ 12 C total fusion, although not quite in the way expected since it leads to a reduction in the cross section, contrary to the trend in the measured $$\left\langle \sigma _\mathrm {F}\right\rangle $$ σ F . However, this result underlines the danger of ignoring the effect of neutron transfer reactions on fusion in systems involving neutron halo nuclei.

Instantons in quantum mechanics (QM)

Perturbative expansion can be generated by calculating Euclidean functional integrals by the steepest descent method always looking, in the absence of external sources, for saddle points in the form of constant solutions to the classical field equations. However, classical field equations may have non-constant solutions. In Euclidean stable field theories, non-constant solutions have always a larger action than minimal constant solutions, because the gradient term gives an additional positive contribution. The non-constant solutions whose action is finite, are called instanton solutions and are the saddle points relevant for a calculation, by the steepest descent method, of barrier penetration effects. This chapter is devoted to simple examples of non-relativistic quantum mechanics (QM), where instanton calculus is an alternative to the semi-classical Wentzel–Kramers–Brillouin (WKB) method. The role of instantons in some metastable systems in QM is explained. In particular, instantons determine the decay rate of metastable states in the semi-classical limit initially confined in a relative minimum of a potential and decaying through barrier penetration. The contributions of instantons at leading order for the quartic anharmonic oscillator with negative coupling are calculate explicitly. The method is generalized to a large class of analytic potentials, and explicit expressions, at leading order, for one-dimensional systems are obtained.