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Nanocrystalline niobium carbide (NbC) ceramics and niobium carbide-niobium nitride (NbC/NbN) composites were synthesized at low temperatures without high-pressure sintering using a single-step polymer-derived approach from a meltable pre-ceramic blend. Niobium hydride (NbH5) and 1,2,4,5-tetrakis(phenylethynyl)benzene (TPEB) reacted at 1500 °C under argon or nitrogen in a tube furnace to form NbC or NbC/NbN with high purities and nanosized grains. Superconductivity measurements indicated that NbC/NbN ceramics exhibited a mixed phase system with two distinct Tc values, and higher elemental niobium content within solids yielded lower Tc. The resulting ceramic monoliths exhibited homogeneous morphologies and controllable amounts of free carbon in the composite matrix. Niobium carbide and nitride composites demonstrated good air oxidation stability up to 450 °C.

Alzheimer’s disease (AD) has several hallmark features including amyloid-β plaque deposits and neuronal loss. Here, we characterized amyloid-β plaque aggregation and parvalbumin-positive (PV) GABAergic neurons in 6 – 9 month old 5xFAD mice harboring mutations associated with familial AD. We used immunofluorescent staining to compare three regions in the frontal cortex – prelimbic (PrL), cingulate (Cg, including Cg1 and Cg2) and secondary motor (M2) cortices – along with primary somatosensory (S1) cortex. We quantified the density of amyloid-β plaques, which showed significant laminar and regional vulnerability. There were more plaques of larger sizes in deep layers compared to superficial layers. Total plaque burden was higher in frontal regions compared to S1. We also found layer- and region-specific differences across genotype in the density of PV interneurons. PV neuron density was lower in 5xFAD mice than wild-type, particularly in deep layers of frontal regions, with Cg (−50%) and M2 (−39%) exhibiting the largest reduction. Using in vivo two-photon imaging, we longitudinally visualized the loss of frontal cortical PV neurons across four weeks in the AD mouse model. Overall, these results provide information about amyloid-β deposits and PV neuron density in a widely used mouse model for AD, implicating deep layers of frontal cortical regions as being especially vulnerable.

With an incidence of ~1 in 800 births, Down syndrome (DS) is the most common chromosomal condition linked to intellectual disability worldwide. While the genetic basis of DS has been identified as a triplication of chromosome 21 (HSA21), the genes encoded from HSA21 that directly contribute to cognitive deficits remain incompletely understood. Here, we found that the HSA21-encoded chromatin effector, BRWD1, was upregulated in neurons derived from iPS cells from an individual with Down syndrome and brain of trisomic mice. We showed that selective copy number restoration of Brwd1 in trisomic animals rescued deficits in hippocampal LTP, cognition and gene expression. We demonstrated that Brwd1 tightly binds the BAF chromatin remodeling complex, and that increased Brwd1 expression promotes BAF genomic mistargeting. Importantly, Brwd1 renormalization rescued aberrant BAF localization, along with associated changes in chromatin accessibility and gene expression. These findings establish BRWD1 as a key epigenomic mediator of normal neurodevelopment and an important contributor to DS-related phenotypes.

A versatile scheme to produce a multiple aromatic ether-linked phthalonitrile has been developed and applied to the preparation of two unique resin systems. The oligomeric phthalonitrile monomer was prepared from the reaction of an excess amount of bisphenol A or bisphenol A6F with 1,3-dibromobenzene in the presence of K 2 CO 3 as the base in a N,N-dimethylformamide/toluene solvent mixture, followed by end-capping with 4-nitrophthalonitrile in a two-step, one-pot reaction. Both phthalonitrile resin systems exhibited excellent viscosities for molding various shaped articles and were thermally cured to yield crosslinked polymers. Each bisphenol-based polymer also demonstrated superb mechanical properties and thermo-oxidative stability while absorbing less than 1% percent water by weight. The two systems differed greatly in their relative reactivity toward the curing additive bis(4-[3-aminophenoxy]phenyl)-sulfone ( m -BAPS). The presence of the electron withdrawing CF 3 groups on the bisphenol A6F resulted in a faster curing reaction to the thermoset polymer but weaker mechanical properties and less overall thermal stability relative to the bisphenol A-containing resin. The bisphenol A6F polymer showed a lower overall water absorption but exhibited a comparable dielectric constant relative to the bisphenol A polymer.

A method to improve the mechanical properties of phthalonitrile (PN) resins at lower postcure temperatures is achieved by blending a second-generation oligomeric aromatic ether ketone-based PN resin with 1,1,1-tris-[4-(3,4-dicyanophenoxy)phenyl]ethane in varying concentrations. Most of the mixtures exhibit a single softening temperature indicating that the two resins are miscibile in one another at the respective concentrations. After various blends are thermally cured to several postcure temperatures yielding crosslinked polymers, the polymers demonstrate superb mechanical properties and thermooxidative stability at lower overall postcure temperatures.

Dopamine (DA) signals originating from substantia nigra (SN) neurons are centrally involved in the regulation of motor and reward processing. DA signals behaviorally relevant events where reward outcomes differ from expectations (reward prediction errors, RPEs). RPEs play a crucial role in learning optimal courses of action and in determining response vigor when an agent expects rewards. Nevertheless, how reward expectations, crucial for RPE calculations, are conveyed to and represented in the dopaminergic system is not fully understood, especially in the human brain where the activity of DA neurons is difficult to study. One possibility, suggested by evidence from animal models, is that DA neurons explicitly encode reward expectations. Alternatively, they may receive RPE information directly from upstream brain regions. To address whether SN neuron activity directly reflects reward expectation information, we directly examined the encoding of reward expectation signals in human putative DA neurons by performing single-unit recordings from the SN of patients undergoing neurosurgery. Patients played a two-armed bandit decision-making task in which they attempted to maximize reward. We show that neuronal firing rates (FR) of putative DA neurons during the reward expectation period explicitly encode reward expectations. First, activity in these neurons was modulated by previous trial outcomes, such that FR were greater after positive outcomes than after neutral or negative outcome trials. Second, this increase in FR was associated with shorter reaction times, consistent with an invigorating effect of DA neuron activity during expectation. These results suggest that human DA neurons explicitly encode reward expectations, providing a neurophysiological substrate for a signal critical for reward learning.