Thermoelectric properties and phase evolution have been studied in biphasic Ti–Ni–Sn materials containing full-Heusler TiNi2Sn embedded within half-Heusler thermoelectric TiNiSn. Materials, prepared by levitation induction melting followed by annealing, were of the nominal starting composition of TiNi1+xSn, with x between 0.00 and 0.25. Phases and microstructure were determined using synchrotron X-ray diffraction and optical and electron microscopy. The full-Heusler phase is observed to be semi-coherent with the half-Heusler majority phase. Differential thermal analysis was performed to determine melting temperatures of the end-member compounds. The thermal conductivity is reduced with the introduction of a dispersed, full-Heusler phase within the half-Heusler material. This leads to an increased thermoelectric figure of merit, ZT, from 0.35 for the stoichiometric compound to 0.44 for TiNi1.15Sn. Beyond x = 0.15 ZT decreases due to a rise in thermal conductivity. Density functional theory calculations using hybrid functionals were performed to determine band alignments between the half- and full-Heusler compounds, as well as comparative energies of formation. The hybrid functional band structure of TiNiSn is presented as well.

Newborns exposed to prenatal opioids often experience intense postnatal withdrawal after cessation of the opioid, called neonatal opioid withdrawal syndrome (NOWS), with limited pre- and postnatal therapeutic options available. In a prior study in pregnant mice we demonstrated that the peripherally selective opioid antagonist, 6β-naltrexol (6BN), is a promising drug candidate for preventive prenatal treatment of NOWS, and a therapeutic mechanism was proposed based on preferential delivery of 6BN to fetal brain with relative exclusion from maternal brain. Here, we have developed methadone (MTD) treated pregnant guinea pigs as a physiologically more suitable model, enabling detection of robust spontaneous neonatal withdrawal. Prenatal MTD significantly aggravates two classic maternal separation stress behaviors in newborn guinea pigs: calling (vocalizing) and searching (locomotion) - natural attachment behaviors thought to be controlled by the endogenous opioid system. In addition, prenatal MTD significantly increases the levels of plasma cortisol in newborns, showing that cessation of MTD at birth engages the hypothalamic-pituitary-adrenal (HPA) axis. We find that co-administration of 6BN with MTD prevents these withdrawal symptoms in newborn pups with extreme potency (ID50 ∼0.02 mg/kg), at doses unlikely to induce maternal or fetal withdrawal or to interfere with opioid antinociception based on many prior studies in rodents and non-human primates. Furthermore, we demonstrate a similarly high potency of 6BN in preventing opioid withdrawal in adult guinea pigs (ID50 = 0.01 mg/kg). This high potency appears to run counter to our pharmacokinetic studies showing slow 6BN transit of both the placenta and maternal blood brain barrier in guinea pigs, and calls into question the preferential delivery mechanism. Rather, it suggests a novel receptor mechanism to account for the selectively high potency of 6BN to suppress opioid dependence at all developmental stages, even in adults, as compared to its well-established low potency as a classical opioid antagonist. In conclusion, 6BN is an attractive compound for development of a preventive therapy for NOWS.