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Abstract Dysregulation of development, migration, and function of interneurons, collectively termed interneuronopathies, have been proposed as a shared mechanism for autism spectrum disorders (ASDs) and childhood epilepsy. Neuropilin-2 (Nrp2), a candidate ASD gene, is a critical regulator of interneuron migration from the median ganglionic eminence (MGE) to the pallium, including the hippocampus. While clinical studies have identified Nrp2 polymorphisms in patients with ASD, whether selective dysregulation of Nrp2-dependent interneuron migration contributes to pathogenesis of ASD and enhances the risk for seizures has not been evaluated. We tested the hypothesis that the lack of Nrp2 in MGE-derived interneuron precursors disrupts the excitation/inhibition balance in hippocampal circuits, thus predisposing the network to seizures and behavioral patterns associated with ASD. Embryonic deletion of Nrp2 during the developmental period for migration of MGE derived interneuron precursors (iCKO) significantly reduced parvalbumin, neuropeptide Y, and somatostatin positive neurons in the hippocampal CA1. Consequently, when compared to controls, the frequency of inhibitory synaptic currents in CA1 pyramidal cells was reduced while frequency of excitatory synaptic currents was increased in iCKO mice. Although passive and active membrane properties of CA1 pyramidal cells were unchanged, iCKO mice showed enhanced susceptibility to chemically evoked seizures. Moreover, iCKO mice exhibited selective behavioral deficits in both preference for social novelty and goal-directed learning, which are consistent with ASD-like phenotype. Together, our findings show that disruption of developmental Nrp2 regulation of interneuron circuit establishment, produces ASD-like behaviors and enhanced risk for epilepsy. These results support the developmental interneuronopathy hypothesis of ASD epilepsy comorbidity. 

Abstract Although Artificial Intelligence (AI) projects are common and desired by many institutions and research teams, there are still relatively few success stories of AI in practical use for the Earth science community. Many AI practitioners in Earth science are trapped in the prototyping stage and their results have not yet been adopted by users. Many scientists are still hesitating to use AI in their research routine. This paper aims to capture the landscape of AI-powered geospatial data sciences by discussing the current and upcoming needs of the Earth and environmental community, such as what practical AI should look like, how to realize practical AI based on the current technical and data restrictions, and the expected outcome of AI projects and their long-term benefits and problems. This paper also discusses unavoidable changes in the near future concerning AI, such as the fast evolution of AI foundation models and AI laws, and how the Earth and environmental community should adapt to these changes. This paper provides an important reference to the geospatial data science community to adjust their research road maps, find best practices, boost the FAIRness (Findable, Accessible, Interoperable, and Reusable) aspects of AI research, and reasonably allocate human and computational resources to increase the practicality and efficiency of Earth AI research. 

Stochastic computing (SC) reduces the complexity of computation by representing numbers with long streams of independent bits. However, increasing performance in SC comes with either an increase in area or a loss in accuracy. Processing in memory (PIM) computes data in-place while having high memory density and supporting bit-parallel operations with low energy consumption. In this article, we propose COSMO, an architecture for co mputing with s tochastic numbers in me mo ry, which enables SC in memory. The proposed architecture is general and can be used for a wide range of applications. It is a highly dense and parallel architecture that supports most SC encodings and operations in memory. It maximizes the performance and energy efficiency of SC by introducing several innovations: (i) in-memory parallel stochastic number generation, (ii) efficient implication-based logic in memory, (iii) novel memory bit line segmenting, (iv) a new memory-compatible SC addition operation, and (v) enabling flexible block allocation. To show the generality and efficiency of our stochastic architecture, we implement image processing, deep neural networks (DNNs), and hyperdimensional (HD) computing on the proposed hardware. Our evaluations show that running DNN inference on COSMO is 141× faster and 80× more energy efficient as compared to GPU. 

ABSTRACT Identification of genes encoding β-lactamases (BLs) from short-read sequences remains challenging due to the high frequency of shared amino acid functional domains and motifs in proteins encoded by BL genes and related non-BL gene sequences. Divergent BL homologs can be frequently missed during similarity searches, which has important practical consequences for monitoring antibiotic resistance. To address this limitation, we built ROCker models that targeted broad classes (e.g., class A, B, C, and D) and individual families (e.g., TEM) of BLs and challenged them with mock 150-bp- and 250-bp-read data sets of known composition. ROCker identifies most-discriminant bit score thresholds in sliding windows along the sequence of the target protein sequence and hence can account for nondiscriminative domains shared by unrelated proteins. BL ROCker models showed a 0% false-positive rate (FPR), a 0% to 4% false-negative rate (FNR), and an up-to-50-fold-higher F1 score [2 × precision × recall/(precision + recall)] compared to alternative methods, such as similarity searches using BLASTx with various e-value thresholds and BL hidden Markov models, or tools like DeepARG, ShortBRED, and AMRFinder. The ROCker models and the underlying protein sequence reference data sets and phylogenetic trees for read placement are freely available through http://enve-omics.ce.gatech.edu/data/rocker-bla . Application of these BL ROCker models to metagenomics, metatranscriptomics, and high-throughput PCR gene amplicon data should facilitate the reliable detection and quantification of BL variants encoded by environmental or clinical isolates and microbiomes and more accurate assessment of the associated public health risk, compared to the current practice. IMPORTANCE Resistance genes encoding β-lactamases (BLs) confer resistance to the widely prescribed antibiotic class β-lactams. Therefore, it is important to assess the prevalence of BL genes in clinical or environmental samples for monitoring the spreading of these genes into pathogens and estimating public health risk. However, detecting BLs in short-read sequence data is technically challenging. Our ROCker model-based bioinformatics approach showcases the reliable detection and typing of BLs in complex data sets and thus contributes toward solving an important problem in antibiotic resistance surveillance. The ROCker models developed substantially expand the toolbox for monitoring antibiotic resistance in clinical or environmental settings.