This paper presents a description of the physical principles of aerodynamic power savings from boundary layer ingestion (BLI) propulsion and a quantitative evaluation of the BLI benefit for advanced civil aircraft. Control volume and one-dimensional analyses are used to illustrate two major features of BLI: reduction of jet mixing losses due to decreased jet kinetic energy from reduced velocity of flow entering the propulsor and, to a lesser extent reduction of airframe wake mixing losses. Embedded BLI propulsion systems can also enable nacelles with reduced surface area and associated weight and drag, further decreasing the aircraft propulsive power requirement. The required propulsor flow power is shown to decrease with increases in both the amount of boundary layer ingested and the propulsor mass flow, and there is thus no unique way to compare BLI and non-BLI systems. Using the ideas presented, however, the benefit can be assessed for any given comparison. The analysis is applied to an advanced civil transport aircraft concept with 40% of the fuselage boundary layer ingested, yielding a reduction in required propulsor mechanical power of 9% relative to a non-BLI configuration with the same propulsors, in agreement with CFD calculations and wind tunnel

Geranylgeranyl reductase from Sulfolobus acidocaldarius was shown to catalyze the reduction of geranylgeranyl groups in the precursors of archaeal membrane lipids, generally reducing all four double bonds. However, when geranylgeranyl diphosphate was subjected to the reductase reaction, only three of the four double bonds were reduced. Mass spectrometry and acid hydrolysis indicated that the allylic double bond was preserved in the partially reduced product derived from geranylgeranyl diphosphate. Thus, the reaction product was shown to be phytyl diphosphate, which is a substrate for archaeal prenyltransferases, unlike the completely reduced compound phytanyl diphosphate.

Behavioral, anatomical, and gene expression studies have shown functional dissociations between the dorsal and ventral hippocampus with regard to their involvement in spatial cognition, emotion, and stress. In this study we examined the difference of the multisynaptic inputs to the dorsal and ventral dentate gyrus (DG) in the rat by using retrograde trans-synaptic tracing of recombinant rabies virus vectors. Three days after the vectors were injected into the dorsal or ventral DG, monosynaptic neuronal labeling was present in the entorhinal cortex, medial septum, diagonal band, and supramammillary nucleus, each of which is known to project to the DG directly. As in previous tracing studies, topographical patterns related to the dorsal and ventral DG were seen in these regions. Five days after infection, more of the neurons in these regions were labeled and labeled neurons were also seen in cortical and subcortical regions, including the piriform and medial prefrontal cortices, the endopiriform nucleus, the claustrum, the cortical amygdala, the medial raphe nucleus, the medial habenular nucleus, the interpeduncular nucleus, and the lateral septum. As in the monosynaptically labeled regions, a topographical distribution of labeled neurons was evident in most of these disynaptically labeled regions. These data indicate that the cortical and subcortical inputs to the dorsal and ventral DG are conveyed through parallel disynaptic pathways. This second-order input difference in the dorsal and ventral DG is likely to contribute to the functional differentiation of the hippocampus along the dorsoventral axis.

Capturing unbound drug exposure in the brain is crucial to evaluate pharmacological effects for drugs acting on the central nervous system. However, to date, there are no reports of validated prediction models to determine the brain-to-plasma unbound concentration ratio (Kp,uu,brain) as well as the cerebrospinal fluid (CSF)-to-plasma unbound concentration ratio (Kp,uu,CSF) between humans and other species. Here, we developed a translational CNS steady-state drug disposition model to predict Kp,uu,brain and Kp,uu,CSF across rats, monkeys, and humans by estimating the relative activity factors (RAF) for MDR1 and BCRP in addition to scaling factors (γ and σ) using the molecular weight, logD, CSF bulk flow, and in vitro transport activities of these transporters. In this study, 68, 26, and 28 compounds were tested in the rat, monkey, and human models, respectively. Both the predicted Kp,uu,brain and Kp,uu,CSF values were within the 3-fold range of the observed values (71, 73, and 79%; 79, 88, and 78% of the compounds, respectively), indicating successful prediction of Kp,uu,brain and Kp,uu,CSF in the three species. The overall predictivity of the RAF approach is consistent with that of the relative expression factor (REF) approach. As the established model can predict Kp,uu,brain and Kp,uu,CSF using only in vitro and physicochemical data, this model would help avoid ethical issues related to animal use and improve CNS drug discovery workflow.

No abstract