In the "Beyond Moore's Law" era, with increasing edge intelligence,domain-specific computing embracing unconventional approaches will becomeincreasingly prevalent. At the same time, adopting a variety ofnanotechnologies will offer benefits in energy cost, computational speed,reduced footprint, cyber resilience, and processing power. The time is ripe fora roadmap for unconventional computing with nanotechnologies to guide futureresearch, and this collection aims to fill that need. The authors provide acomprehensive roadmap for neuromorphic computing using electron spins,memristive devices, two-dimensional nanomaterials, nanomagnets, and variousdynamical systems. They also address other paradigms such as Ising machines,Bayesian inference engines, probabilistic computing with p-bits, processing inmemory, quantum memories and algorithms, computing with skyrmions and spinwaves, and brain-inspired computing for incremental learning andproblem-solving in severely resource-constrained environments. These approacheshave advantages over traditional Boolean computing based on von Neumannarchitecture. As the computational requirements for artificial intelligencegrow 50 times faster than Moore's Law for electronics, more unconventionalapproaches to computing and signal processing will appear on the horizon, andthis roadmap will help identify future needs and challenges. In a very fertilefield, experts in the field aim to present some of the dominant and mostpromising technologies for unconventional computing that will be around forsome time to come. Within a holistic approach, the goal is to provide pathwaysfor solidifying the field and guiding future impactful discoveries.
The essential metal manganese (Mn) induces neuromotor disease at elevated levels. The manganese efflux transporter SLC30A10 regulates brain Mn levels. Homozygous loss-of-function mutations in SLC30A10 induce hereditary Mn neurotoxicity in humans. Our prior characterization of Slc30a10 knockout mice recapitulated the high brain Mn levels and neuromotor deficits reported in humans. But, mechanisms of Mn-induced motor deficits due to SLC30A10 mutations or elevated Mn exposure are unclear. To gain insights into this issue, we characterized changes in gene expression in the basal ganglia, the main brain region targeted by Mn, of Slc30a10 knockout mice using unbiased transcriptomics. Compared with littermates, >1000 genes were upregulated or downregulated in the basal ganglia sub-regions (i.e. caudate putamen, globus pallidus, and substantia nigra) of the knockouts. Pathway analyses revealed notable changes in genes regulating synaptic transmission and neurotransmitter function in the knockouts that may contribute to the motor phenotype. Expression changes in the knockouts were essentially normalized by a reduced Mn chow, establishing that changes were Mn dependent. Upstream regulator analyses identified hypoxia-inducible factor (HIF) signaling, which we recently characterized to be a primary cellular response to elevated Mn, as a critical mediator of the transcriptomic changes in the basal ganglia of the knockout mice. HIF activation was also evident in the liver of the knockout mice. These results: (i) enhance understanding of the pathobiology of Mn-induced motor disease; (ii) identify specific target genes/pathways for future mechanistic analyses; and (iii) independently corroborate the importance of the HIF pathway in Mn homeostasis and toxicity.