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BACKGROUND: Autism spectrum disorder involves neurodevelopmental dysregulations that lead to visible symptoms at early stages of life. Many autism spectrum disorder-related mechanisms suggested by animal studies are supported by demonstrated improvement in autistic-like phenotypes in adult animals following experimental reversal of dysregulated mechanisms. However, whether such mechanisms also act at earlier stages to cause autistic-like phenotypes is unclear. METHODS: We used Shank2-/- mice carrying a mutation identified in human autism spectrum disorder (exons 6 and 7 deletion) and combined electrophysiological and behavioral analyses to see whether early pathophysiology at pup stages is different from late pathophysiology at juvenile and adult stages and whether correcting early pathophysiology can normalize late pathophysiology and abnormal behaviors in juvenile and adult mice. RESULTS: Early correction of a dysregulated mechanism in young mice prevents manifestation of autistic-like social behaviors in adult mice. Shank2-/- mice, known to display N-methyl-D-aspartate receptor (NMDAR) hypofunction and autistic-like behaviors at postweaning stages after postnatal day 21 (P21), show the opposite synaptic phenotype-NMDAR hyperfunction-at an earlier preweaning stage (∼P14). Moreover, this NMDAR hyperfunction at P14 rapidly shifts to NMDAR hypofunction after weaning (∼P24). Chronic suppression of the early NMDAR hyperfunction by the NMDAR antagonist memantine (P7-P21) prevents NMDAR hypofunction and autistic-like social behaviors from manifesting at later stages (∼P28 and P56). CONCLUSIONS: Early NMDAR hyperfunction leads to late NMDAR hypofunction and autistic-like social behaviors in Shank2-/- mice, and early correction of NMDAR dysfunction has the long-lasting effect of preventing autistic-like social behaviors from developing at later stages.

Decoupling dynamic touch signals in the optical tactile sensors is highly desired for behavioral tactile applications yet challenging because typical optical sensors mostly measure only static normal force and use imprecise multi-image averaging for dynamic force sensing. Here, we report a highly sensitive upconversion nanocrystals-based behavioral biometric optical tactile sensor that instantaneously and quantitatively decomposes dynamic touch signals into individual components of vertical normal and lateral shear force from a single image in real-time. By mimicking the sensory architecture of human skin, the unique luminescence signal obtained is axisymmetric for static normal forces and non-axisymmetric for dynamic shear forces. Our sensor demonstrates high spatio-temporal screening of small objects and recognizes fingerprints for authentication with high spatial-temporal resolution. Using a dynamic force discrimination machine learning framework, we realized a Braille-to-Speech translation system and a next-generation dynamic biometric recognition system for handwriting. A sensitive upconversion nanocrystal-based biometric optical tactile sensor instantaneously and quantitatively decomposes dynamic touch signals into individual components of vertical normal and lateral shear force from a single image in real-time. [ABSTRACT FROM AUTHOR]

UNLABELLED: Shank2 is a multidomain scaffolding protein implicated in the structural and functional coordination of multiprotein complexes at excitatory postsynaptic sites as well as in psychiatric disorders, including autism spectrum disorders. While Shank2 is strongly expressed in the cerebellum, whether Shank2 regulates cerebellar excitatory synapses, or contributes to the behavioral abnormalities observed in Shank2-/- mice, remains unexplored. Here we show that Shank2-/- mice show reduced excitatory synapse density in cerebellar Purkinje cells in association with reduced levels of excitatory postsynaptic proteins, including GluD2 and PSD-93, and impaired motor coordination in the Erasmus test. Shank2 deletion restricted to Purkinje cells (Pcp2-Cre;Shank2fl/fl mice) leads to similar reductions in excitatory synapse density, synaptic protein levels, and motor coordination. Pcp2-Cre;Shank2fl/fl mice do not recapitulate autistic-like behaviors observed in Shank2-/- mice, such as social interaction deficits, altered ultrasonic vocalizations, repetitive behaviors, and hyperactivity. However, Pcp2-Cre;Shank2fl/fl mice display enhanced repetitive behavior in the hole-board test and anxiety-like behavior in the light-dark test, which are not observed in Shank2-/- mice. These results implicate Shank2 in the regulation of cerebellar excitatory synapse density, motor coordination, and specific repetitive and anxiety-like behaviors. SIGNIFICANCE STATEMENT: The postsynaptic side of excitatory synapses contains multiprotein complexes, termed the postsynaptic density, which contains receptors, scaffolding/adaptor proteins, and signaling molecules. Shank2 is an excitatory postsynaptic scaffolding protein implicated in the formation and functional coordination of the postsynaptic density and has been linked to autism spectrum disorders. Using Shank2-null mice and Shank2-conditional knock-out mice with a gene deletion restricted to cerebellar Purkinje cells, we explored functions of Shank2 in the cerebellum. We found that Shank2 regulates excitatory synapse density, motor coordination, and specific repetitive and anxiety-like behaviors, but is not associated with autistic-like social deficits or repetitive behaviors.

Semiconductor industry is experiencing a rising demand for environmentally friendly processes with the emphasis on green policies and worldwide environmental sustainability. Nitrogen trifluoride (NF3), the most common plasma chamber cleaning agent gas, poses a significant concern as a potent greenhouse gas since it has global warming potential (GWP), 740 times and 6 times higher than that CO2 and N2O. This study investigated the exhaust gas using quadrupole mass spectroscopy (QMS) and analyzed the change in cleaning speed and the type of exhaust gas through plasma monitoring using optical mass spectroscopy (OES). The objective is to lower the use of the amount of NF3 gas in chamber cleaning process to partially contribute the environmental sustainability in the point of semiconductor manufacturing. When a small amount of N2 was added to NF3 whose ratio of 7:23, the cleaning efficiency reached to 90% compared to NF3 gas alone. Addition of N2 positively affected electron density and temperature to increase the F-radical in remote plasma system. In conclusion, 18% of NF3 usage amount was reduced during the Sio2 deposition chamber cleaning process. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a group of conditions characterized by impaired social interaction and communication, and restricted and repetitive behaviours. ASD is a highly heritable disorder involving various genetic determinants (1). Shank2 (also known as ProSAP1) is a multi-domain scaffolding protein and signalling adaptor enriched at excitatory neuronal synapses (2-4), and mutations in the human SHANK2 gene have recently been associated with ASD and intellectual disability5. Although ASD-associated genes are being increasingly identified and studied using various approaches, including mouse genetics6-16, further efforts are required to delineate important causal mechanisms with the potential for therapeutic application. Here we show that Shank2-mutant ([Shank2.sup.-/-]) mice carrying a mutation identical to the ASD-associated microdeletion in the human SHANK2gene exhibit ASD-like behaviours including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping. These mice show a marked decrease in NMDA (N-methyl-D-aspartate) glutamate receptor (NMDAR) function. Direct stimulation of NMDARs with D-cycloserine, a partial agonist of NMDARs, normalizes NMDAR function and improves social interaction in [Shank2.sup.-/-] mice. Furthermore, treatment of [Shank2.sup.-/-] mice with a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), which enhances NMDAR function via mGluR5 activation17, also normalizes NMDAR function and markedly enhances social interaction. These results suggest that reduced NMDAR function may contribute to the development of ASD-like phenotypes in [Shank2.sup.-/-] mice, and mGluR modulation of NMDARs offers a potential strategy to treat ASD., Mutations in the SHANK2 gene have recently been identified in individuals with ASD and intellectual disability (5,18). Among these mutations, one de novo SHANK2 microdeletion found in ASD leads to [...]

Upconversion nanocrystals (UCNs)‐embedded microarchitectures with luminescence color transition capability and enhanced luminescence intensity under extreme conditions are suitable for developing a robust labeling system in a high‐temperature thermal industrial process. However, most UCNs based labeling systems are limited by the loss of luminescence owing to the destruction of the crystalline phase or by a predetermined luminescence color without color transition capability. Herein, an unusual crystal phase transition of UCNs to a hexagonal apatite phase in the presence of SiO2 nanoparticles is reported with the enhancements of 130‐fold green luminescence and 52‐fold luminance as compared to that of the SiO2‐free counterpart. By rationally combining this strategy with an additive color mixing method using a mask‐less flow lithography technique, single to multiple luminescence color transition, scalable labeling systems with hidden letters‐, and multi‐luminescence colored microparticles are demonstrated for a UCNs luminescence color change‐based high temperature labeling system. [ABSTRACT FROM AUTHOR]