Moiré synaptic transistor with room-temperature neuromorphic functionality.

Moiré quantum materials host exotic electronic phenomena through enhanced internal Coulomb interactions in twisted two-dimensional heterostructures1-4. When combined with the exceptionally high electrostatic control in atomically thin materials5-8, moiré heterostructures have the potential to enable next-generation electronic devices with unprecedented functionality. However, despite extensive exploration, moiré electronic phenomena have thus far been limited to impractically low cryogenic temperatures9-14, thus precluding real-world applications of moiré quantum materials. Here we report the experimental realization and room-temperature operation of a low-power (20 pW) moiré synaptic transistor based on an asymmetric bilayer graphene/hexagonal boron nitride moiré heterostructure. The asymmetric moiré potential gives rise to robust electronic ratchet states, which enable hysteretic, non-volatile injection of charge carriers that control the conductance of the device. The asymmetric gating in dual-gated moiré heterostructures realizes diverse biorealistic neuromorphic functionalities, such as reconfigurable synaptic responses, spatiotemporal-based tempotrons and Bienenstock-Cooper-Munro input-specific adaptation. In this manner, the moiré synaptic transistor enables efficient compute-in-memory designs and edge hardware accelerators for artificial intelligence and machine learning.

Exome Sequencing Implicates DGKZ , ESRRA , and GXYLT1 for Modulating Granuloma Formation in Crohn Disease.

Non-caseating granulomas may indicate a more aggressive phenotype of Crohn disease (CD). Genetic associations of granulomatous CD (GCD) may help elucidate disease pathogenesis. Whole-exome sequencing was performed on peripheral blood-derived DNA from 17 pediatric patients with GCD and 19 with non-GCD (NGCD), and from an independent validation cohort of 44 GCD and 19 NGCD cases. PLINK (a tool set for whole-genome association and population-based linkage analyses) analysis was used to identify single nucleotide polymorphisms (SNPs) differentiating between groups, and subgroup allele frequencies were also compared to a public genomic database (gnomAD). The Combined Annotation Dependent Depletion scoring tool was used to predict deleteriousness of SNPs. Human leukocyte antigen (HLA) haplotype findings were compared to a control group (n = 8496). PLINK-based analysis between GCD and NGCD groups did not find consistently significant hits. gnomAD control comparisons, however, showed consistent subgroup associations with DGKZ , ESRRA , and GXYLT1 , genes that have been implicated in mammalian granulomatous inflammation. Our findings may guide future research and precision medicine.

Centrifuge-Free Separation of Solution-Exfoliated 2D Nanosheets via Cross-Flow Filtration.

Solution-processed graphene is a promising material for numerous high-volume applications including structural composites, batteries, sensors, and printed electronics. However, the polydisperse nature of graphene dispersions following liquid-phase exfoliation poses major manufacturing challenges, as incompletely exfoliated graphite flakes must be removed to achieve optimal properties and downstream performance. Incumbent separation schemes rely on centrifugation, which is highly energy-intensive and limits scalable manufacturing. Here, cross-flow filtration (CFF) is introduced as a centrifuge-free processing method that improves the throughput of graphene separation by two orders of magnitude. By tuning membrane pore sizes between microfiltration and ultrafiltration length scales, CFF can also be used for efficient recovery of solvents and stabilizing polymers. In this manner, life cycle assessment and techno-economic analysis reveal that CFF reduces greenhouse gas emissions, fossil energy usage, water consumption, and specific production costs of graphene manufacturing by 57%, 56%, 63%, and 72%, respectively. To confirm that CFF produces electronic-grade graphene, CFF-processed graphene nanosheets are formulated into printable inks, leading to state-of-the-art thin-film conductivities exceeding 104 S m-1 . This CFF methodology can likely be generalized to other van der Waals layered solids, thus enabling sustainable manufacturing of the diverse set of applications currently being pursued for 2D materials.

Racial and Ethnic Variation in Presentation, Diagnosis, Treatment, and Outcome of Pediatric Crohn Disease: A Single Center Study.

OBJECTIVES: Disparities in health care for racial/ethnic minority children in the United States who are burdened by pediatric Crohn's disease (PCD) are not well understood. METHODS: A retrospective review of the Texas Children's Hospital ImproveCareNow database from 2007 to 2015 was performed. CD patients with a minimum of 2-year follow-up were included if the onset of symptoms attributable to inflammatory bowel disease was clearly documented. We primarily aimed to identify race and ethnicity associations in diagnostic delay, presentation, treatment, and 2-year outcomes. We also examined early versus late diagnosis (ie, over 6 months from disease onset) associations with these variables unrelated to race/ethnicity. RESULTS: One hundred and sixty-six PCD patients [57.8% non-Hispanic White (NH-White), 18.1% African American (AA), and 15.7% Hispanic] met selection criteria. Time to diagnosis was shorter in Hispanic patients ( P < 0.01) and they were older at diagnosis than NH-White patients ( P = 0.0164). AA patients (33%, P < 0.01) and Hispanic patients (35%, P < 0.05) had lower rates of granuloma detection than NH-White patients (63%). AA patients had lower rates of steroid-free remission (SFR) at 2 years than NH-White patients ( P < 0.05). Higher ESR and lower hemoglobin levels were associated with early diagnosis ( P < 0.01). Early diagnosis was associated with higher rates of surgery within 2 years of diagnosis ( P < 0.05). Diagnostic fecal calprotectin levels inversely associated with SFR at 2 years ( P < 0.05). Early use of biologics positively, and early use of corticosteroids negatively correlated with 2-year SFR ( P < 0.05). CONCLUSIONS: Race and ethnicity may influence the diagnosis, treatment, and outcomes of PCD. This recognition presents a nidus toward establishing equity in PCD care.

Progress and Challenges for Memtransistors in Neuromorphic Circuits and Systems.

Due to the increasing importance of artificial intelligence (AI), significant recent effort has been devoted to the development of neuromorphic circuits that seek to emulate the energy-efficient information processing of the brain. While non-volatile memory (NVM) based on resistive switches, phase-change memory, and magnetic tunnel junctions has shown potential for implementing neural networks, additional multi-terminal device concepts are required for more sophisticated bio-realistic functions. Of particular interest are memtransistors based on low-dimensional nanomaterials, which are capable of electrostatically tuning memory and learning behavior at the device level. Herein, a conceptual overview of the memtransistor is provided in the context of neuromorphic circuits. Recent progress is surveyed for memtransistors and related multi-terminal NVM devices including dual-gated floating-gate memories, dual-gated ferroelectric transistors, and dual-gated van der Waals heterojunctions. The different materials systems and device architectures are classified based on the degree of control and relative tunability of synaptic behavior, with an emphasis on device concepts that harness the reduced dimensionality, weak electrostatic screening, and phase-changes properties of nanomaterials. Finally, strategies for achieving wafer-scale integration of memtransistors and multi-terminal NVM devices are delineated, with specific attention given to the materials challenges for practical neuromorphic circuits.

Diagnostic delay and colectomy risk in pediatric ulcerative colitis.

BACKGROUND/PURPOSE: Diagnostic delay or time to diagnosis, and its relationship with colectomy risk has been studied in adult Inflammatory Bowel Disease (IBD), but rarely in pediatric IBD (PIBD), especially pediatric ulcerative colitis (P-UC), which often has a more severe course than adult UC. This study compared the relationship between diagnostic delay and colectomy in P-UC. METHODS: The medical records of P-UC patients, ages <18 years, diagnosed at Texas Children's Hospital from 2012 to 2018 were examined. We identified 106 P-UC patients, where the onset of symptoms of IBD (i.e. fever, diarrhea, blood in stool, weight loss, abdominal pain) could be clearly identified. RESULTS: Twenty (20 = 18.9%) patients progressed to colectomy, and 86 did not. There was no significant difference in diagnostic delay between the patients undergoing colectomy with UC (C-UC) and those with no colectomy (NC-UC) (p = 0.2192). The median (C-UC = 7.1 weeks; NC-UC = 11.9 weeks) and mean (C-UC = 16.5 weeks±4.7; NC-UC = 20.1 ±â€¯2.6) diagnostic delay actually tended to be shorter in C-UC compared to NC-UC. Fecal calprotectin levels were significantly higher (p = 0.0228) in C-UC than NC-UC patients at diagnosis. CONCLUSIONS: Shorter time to diagnosis may reflect disease severity at the time of disease onset and also a more aggressive subsequent course of P-UC. The significantly higher level of fecal calprotectin in the C-UC patients at diagnosis provided biologic/biochemical support for our conclusion. LEVELS OF EVIDENCE: Prognosis study, Level III evidence.

Non-monotonic dose-response effects of arsenic on glucose metabolism.

BACKGROUND: Inorganic arsenic (iAs) is a widespread environmental toxin. In addition to being a human carcinogen, its effect on diabetes has started to gain recognition recently. Insulin is the key hormone regulating systemic glucose metabolism. The in vivo effect of iAs on insulin sensitivity has not been directly addressed. OBJECTIVES: Here we use mouse models to dissect the dose-dependent effects of iAs on glucose metabolism in vivo. METHODS: We performed hyperinsulinemic-euglycemic clamp, the gold standard analysis of systemic insulin sensitivity. We also performed dynamic metabolic testings and RNA-seq analysis. RESULTS: We found that a low-dose exposure (0.25 ppm iAs in drinking water) caused glucose intolerance in adult male C57BL/6 mice, likely by disrupting glucose-induced insulin secretion without affecting peripheral insulin sensitivity. However, a higher-dose exposure (2.5 ppm iAs) had diminished effects on glucose tolerance despite disrupted pancreatic insulin secretion. Insulin Clamp analysis showed that 2.5 ppm iAs actually enhanced systemic insulin sensitivity by simultaneously enhancing insulin-stimulated glucose uptake in skeletal muscles and improved insulin-mediated suppression of endogenous glucose production. RNA-seq analysis of skeletal muscles revealed that 2.5 ppm iAs regulated expression of many genes involved in the metabolism of fatty acids, pyruvate, and amino acids. CONCLUSION: These findings suggest that iAs has opposite glycemic effects on distinct metabolic tissues at different dose thresholds. Such non-monotonic dose-response effects of iAs on glucose tolerance shed light on the complex interactions between iAs and the systemic glucose metabolism, which could potentially help reconcile some of the conflicting results in human epidemiological studies.

Integrated omics approaches to characterize a nuclear receptor corepressor-associated histone deacetylase in mouse skeletal muscle.

Nuclear receptors regulate gene expression by differentially binding to coactivators or corepressors in a ligand-dependent manner, which further recruits a set of epigenome-modifying enzymes that remodel chromatin conformation. Histone acetylation is a major epigenomic change controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDAC3 is the only HDAC that confers the enzymatic activity to the complexes nucleated by nuclear receptor corepressors NCoR and SMRT. To address the metabolic function of HDAC3, we have deleted it specifically in mouse skeletal muscles. We have performed the following omics profiling in skeletal muscles of these mice: (1) RNA-seq profiling of total RNA; (2) Global nuclear run-on (GRO-seq) analysis of nascent RNAs; (3) Chromatin immuno-precipitation (ChIP-seq) of HDAC3 at both early evening and early morning; (4) proteomics profiling with mass spectrometry; (5) snap-shot metabolomics profiling of water-soluble metabolites at the basal condition; (6) snap-shot metabolomics profiling of lipid species at the basal condition; (7) kinetic fluxomics analysis of glucose utilization using 13C6-glucose In vivo during treadmill running exercise. These approaches have provided several novel insights into how nuclear receptors regulate circadian rhythm of skeletal muscle fuel metabolism, which has been published elsewhere. Here we present the original datasets and technical details during the execution, analysis, and interpretation of these omics studies.