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With the rapid development of integrated circuits, glass substrates are frequently utilized for prototyping various functional electronic circuits due to their superior stability, transparency, and signal integrity. In this experiment, copper wire was printed on a glass substrate using inkjet printing, and the electronic circuit was sintered through laser irradiation with a 532 nm continuous green laser. The relationship between resistivity and microstructure was analyzed after laser sintering at different intensities, scanning speeds, and iterations. The experimental results indicate that the conductivity of the sintered lines initially increases and then decreases with an increase in laser power and scanning speed. At the same power level, multiple sintering runs at a lower scanning speed pose a risk of increased porosity leading to reduced conductivity. Conversely, when the scanning speed exceeds the optimal sintering speed, multiple sintering runs have minimal impact on porosity and conductivity without altering the power.

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The UBE3A gene, located in the chromosomal region 15q11-13, is subject to neuron-specific genomic imprinting and it plays a critical role in brain development. Genetic defects of UBE3A cause severe neurodevelopmental disorders, namely the Angelman syndrome (AS) and the 15q11.2-q13.3 duplication syndrome (Dup15q). In the last two decades, the development of in vitro and in vivo models of AS and Dup15q were fundamental to improve the understanding of UBE3A function in the brain. However, the pathogenic mechanisms of these diseases remain elusive and effective treatments are lacking. Recent evidence suggests that UBE3A functions are both spatially and temporally specific, varying across subcellular compartments, brain regions, and neuronal circuits. In the present review, we summarize current knowledge on the role of UBE3A in neuronal pathophysiology under this spatio-temporal perspective. Additionally, we propose key research questions that will be instrumental to better understand the pathogenic mechanisms underpinning AS and Dup15q disorders and provide the rationale to develop novel therapies.

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Waste integrated circuits, with underlying resource attributes and environmental risks, are complex in composition. Current processes suffer from high resource inputs, excessive pollutant emissions and incomplete treatment of varied species. Therefore, a comprehensive resource recycling and safe disposal process integrated with precious metal enrichment, non-metal resource utilization, and organic detoxification was proposed. The copper and non-metals from waste ICs served as in-situ precious metal collector, slagging former and reducing agent for alternative to partial chemical inputs. Batch experiments indicated that optimized parameters enabled the recycling efficiencies of 94.3 %, 96.8 % and 98.4 % for copper, gold and silver, respectively. Meanwhile, oxide component, yielded as silicate slag, was synthesized into glass ceramics via high-temperature sintering. Furthermore, organic conversion process revealed that high-temperature smelting catalyzed bromine removal and contaminant detoxification, with decomposed reductive hydrocarbons facilitating metal capture in turn. And the capture mechanism was disclosed form thermodynamics and microdroplet motion perspectives. As process evaluation indicates, proposed recycling route allows remarkable reductions in negative environmental response and economic investment. In this work, metal recycling, waste minimization and pollutant detoxification were attained synergistically without residue, which contributes a novel insight into the disposal of comparable e-wastes.

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Here, a unique crossbar architecture is designed and fabricated, incorporating vertically integrated self-assembled monolayers in electronic devices. This architecture is used to showcase 100 individual vertical molecular junctions on a single chip with a high yield of working junctions and high device uniformity. The study introduces a transfer approach for patterned liquid-metal eutectic alloy of gallium and indium top electrodes, enabling the creation of fully flexible molecular devices with electrical functionalities. The devices exhibit excellent charge transport performance, sustain a high rectification ratio (>103), and stable endurance and retention properties, even when the devices are significantly bent. Furthermore, Boolean logic gates, including OR and AND gates, as well as half-wave and full-wave rectifying circuits, are successfully implemented. The unique design of the flexible molecular device represents a significant step in harnessing the potential of molecular devices for high-density integration and possible molecule-based computing.

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DNA amplifier circuits establish powerful tools to dynamically control molecular assembly for computation, sensing, and biological applications. However, the slow reaction speed remains a major barrier to their practical utility. Here, diverse fast DNA amplifier circuits termed toehold exchange polymerization (TEP) and toehold exchange catalysis (TEC) using toehold exchange-mediated assembly as a fundamental mechanism are built. Both TEP and TEC with a duplex and a hairpin can respond within minutes to diverse nucleic acid inputs with high fidelity. In addition, the circuits can amplify live-cell signals for fluorescence imaging target RNA dynamics and discriminating different cell lines. Compared with existing DNA circuits that involve time scales of hours for transducing small signals, TEP and TEC exhibit much faster dynamics, simpler design, and comparable sensitivity. These features make TEP and TEC promising platforms to develop programmable nucleic acid tools and devices and to create fast sensing and processing systems, amenable to wide practical applications.

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The cloning of leptin 30 years ago in 1994 was an important milestone in obesity research. Prior to the discovery of leptin, obesity was stigmatized as a condition caused by lack of character and self-control. Mutations in either leptin or its receptor were the first single gene mutations found to cause severe obesity, and it is now recognized that obesity is caused mostly by a dysregulation of central neuronal circuits. Since the discovery of the leptin-deficient obese mouse (ob/ob) the cloning of leptin (ob aka lep) and leptin receptor (db aka lepr) genes, we have learned much about leptin and its action in the central nervous system. The first hope that leptin would cure obesity was quickly dampened because humans with obesity have increased leptin levels and develop leptin resistance. Nevertheless, leptin target sites in the brain represent an excellent blueprint to understand how neuronal circuits control energy homeostasis. Our expanding understanding of leptin function, interconnection of leptin signaling with other systems and impact on distinct physiological functions continues to guide and improve the development of safe and effective interventions to treat metabolic illnesses. This review highlights past concepts and current emerging concepts of the hormone leptin, leptin receptor signaling pathways and central targets to mediate distinct physiological functions.

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Single-photon avalanche diodes (SPADs) belong to a family of avalanche photodiodes (APDs) with single-photon detection capability that operate above the breakdown voltage (i.e., Geiger mode). Design and technology constraints, such as dark current, photon detection probability, and power dissipation, impose inherent device limitations on avalanche photodiodes. Moreover, after the detection of a photon, SPADs require dead time for avalanche quenching and recharge before they can detect another photon. The reduction in dead time results in higher efficiency for photon detection in high-frequency applications. In this work, an electronic interface, based on the pole-zero compensation technique for reducing dead time, was investigated. A nanosecond pulse generator was designed and fabricated to generate pulses of comparable voltage to an avalanche transistor. The quenching time constant (τq) is not affected by the compensation capacitance variation, while an increase of about 30% in the τq is related to the properties of the specific op-amp used in the design. Conversely, the recovery time was observed to be strongly influenced by the compensation capacitance. Reductions in the recovery time, from 927.3 ns down to 57.6 ns and 9.8 ns, were observed when varying the compensation capacitance in the range of 5-0.1 pF. The experimental results from an SPAD combined with an electronic interface based on an avalanche transistor are in strong accordance, providing similar output pulses to those of an illuminated SPAD.

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The design-build-test-learn workflow is pivotal in synthetic biology as it seeks to broaden access to diverse levels of expertise and enhance circuit complexity through recent advancements in automation. The design of complex circuits depends on developing precise models and parameter values for predicting the circuit performance and noise resilience. However, obtaining characterized parameters under diverse experimental conditions is a significant challenge, often requiring substantial time, funding, and expertise. This work compares five computational models of three different genetic circuit implementations of the same logic function to evaluate their relative predictive capabilities. The primary focus is on determining whether simpler models can yield conclusions similar to those of more complex ones and whether certain models offer greater analytical benefits. These models explore the influence of noise, parametrization, and model complexity on predictions of synthetic circuit performance through simulation. The findings suggest that when developing a new circuit without characterized parts or an existing design, any model can effectively predict the optimal implementation by facilitating qualitative comparison of designs' failure probabilities (e.g., higher or lower). However, when characterized parts are available and accurate quantitative differences in failure probabilities are desired, employing a more precise model with characterized parts becomes necessary, albeit requiring additional effort.

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Large-scale multimodal neural recordings on high-density biosensing microelectrode arrays (HD-MEAs) offer unprecedented insights into the dynamic interactions and connectivity across various brain networks. However, the fidelity of these recordings is frequently compromised by pervasive noise, which obscures meaningful neural information and complicates data analysis. To address this challenge, we introduce DENOISING, a versatile data-derived computational engine engineered to adjust thresholds adaptively based on large-scale extracellular signal characteristics and noise levels. This facilitates the separation of signal and noise components without reliance on specific data transformations. Uniquely capable of handling a diverse array of noise types (electrical, mechanical, and environmental) and multidimensional neural signals, including stationary and non-stationary oscillatory local field potential (LFP) and spiking activity, DENOISING presents an adaptable solution applicable across different recording modalities and brain networks. Applying DENOISING to large-scale neural recordings from mice hippocampal and olfactory bulb networks yielded enhanced signal-to-noise ratio (SNR) of LFP and spike firing patterns compared to those computed from raw data. Comparative analysis with existing state-of-the-art denoising methods, employing SNR and root mean square noise (RMS), underscores DENOISING's performance in improving data quality and reliability. Through experimental and computational approaches, we validate that DENOISING improves signal clarity and data interpretation by effectively mitigating independent noise in spatiotemporally structured multimodal datasets, thus unlocking new dimensions in understanding neural connectivity and functional dynamics.

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BACKGROUND: Grating orientation discrimination (GOD) is commonly used to assess somatosensory spatial processing. It allows discrimination between parallel and orthogonal orientations of tactile stimuli applied to the fingertip. Despite its widespread application, the underlying mechanisms of GOD, particularly the role of cortico-cortical interactions and local brain activity in this process, remain elusive. Therefore, we aimed to investigate how a specific cortico-cortical network and inhibitory circuits within the primary somatosensory cortex (S1) and secondary somatosensory cortex (S2) contribute to GOD. METHODS: In total, 51 healthy young adults were included in our study. We recorded resting-state magnetoencephalography (MEG) and somatosensory-evoked magnetic field (SEF) in participants with open eyes. We converted the data into a source space based on individual structural magnetic resonance imaging. Next, we estimated S1- and S2-seed resting-state functional connectivity (rs-FC) at the alpha and beta bands through resting-state MEG using the amplitude envelope correlation method across the entire brain (i.e., S1/S2-seeds × 15,000 vertices × two frequencies). We assessed the inhibitory response in the S1 and S2 from SEFs using a paired-pulse paradigm. We automatically measured the GOD task in parallel and orthogonal orientations to the index finger, applying various groove widths with a custom-made device. RESULTS: We observed a specific association between the GOD threshold (all P < 0.048) and the alpha rs-FC in the S1-superior parietal lobule and S1-adjacent to the parieto-occipital sulcus (i.e., lower rs-FC values corresponded to higher performance). In contrast, no association was observed between the local responses and the threshold. DISCUSSION: The results of this study underpin the significance of specific cortico-cortical networks in recognizing variations in tactile stimuli.

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Optical encoders are widely used circuits in digital systems. One of the most critical features of an optical encoder is the power values in two logic states; low and high. The difference between these two values is expressed with the contrast ratio (CR) parameter. This research has designed and simulated an optical encoder based on a two-dimensional (2D) photonic crystal with four inputs and two outputs. The results show that the proposed structure has low power in low mode and high intensity in high mode. This difference in two logical modes has caused the proposed encoder to have CR = 19.8 dB, which is improved compared to previous works. Also, the proposed structure is very compact and its footprint is as small as 96.88 µm2. The data speed for the designed encoder is B R = 2 Tb/s . This encoder can be used in high-speed optical integrated circuits with low error according to the obtained values.

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Myelination of axons is a key determinant of fast action potential propagation, axonal health and circuit function. Previously considered a static structure, it is now clear that myelin is dynamically regulated in response to neuronal activity in the CNS. However, how activity-dependent signals are conveyed to oligodendrocytes remains unclear. Here we review the potential mechanisms by which neurons could communicate changing activity levels to myelin, with a focus on the accumulating body of evidence to support activity-dependent vesicular signalling directly onto myelin sheaths. We discuss recent in vivo findings of activity-dependent fusion of neurotransmitter vesicles from non-synaptic axonal sites, and how modulation of this vesicular fusion regulates the stability and growth of myelin sheaths. We also consider the potential mechanisms by which myelin could sense and respond to axon-derived signals to initiate remodelling, and the relevance of these adaptations for circuit function. We propose that axonal vesicular signalling represents an important and underappreciated mode of communication by which neurons can transmit activity-regulated signals to myelinating oligodendrocytes and, potentially, more broadly to other cell types in the CNS.

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Autism spectrum disorder (ASD) has proven to be highly enigmatic due to the diversity of its underlying genetic causes and the huge variability in symptom presentation. Uncovering common phenotypes across people with ASD and pre-clinical models allows us to better understand the influence on brain function of the many different genetic and cellular processes thought to contribute to ASD aetiology. One such feature of ASD is the convergent evidence implicating abnormal functioning of the medial prefrontal cortex (mPFC) across studies. The mPFC is a key part of the 'social brain' and may contribute to many of the changes in social behaviour observed in people with ASD. Here we review recent evidence for mPFC involvement in both ASD and social behaviours. We also highlight how pre-clinical mouse models can be used to uncover important cellular and circuit-level mechanisms that may underly atypical social behaviours in ASD. This article is part of the Special Issue on "PFC circuit function in psychiatric disease and relevant models".

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An on-chip asymmetric directional coupler (DC) can convert fundamental modes to higher-order modes and is one of the core components of mode-division multiplexing (MDM) technology. In this study, we propose that waveguides of the asymmetric DC can be trimmed by silicon ion implantation to tune the effective refractive index and facilitate mode conversion into higher-order modes. Through this method of tuning, transmission changes of up to 18 dB have been realized with one ion implantation step. In addition, adjusting the position of the ion implantation on the waveguide can provide a further degree of control over the transmission into the resulting mode. The results of this work present a promising new route for the development of high-efficiency, low-loss mode converters for integrated photonic platforms, and aim to facilitate the application of MDM technology in emerging photonic neuromorphic computing.

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Building on and extending existing definitions of robustness and evolvability, we propose and utilize new formal definitions, with matching measures, of robustness and evolvability of systems with genotypes and corresponding phenotypes. We explain and show how these measures are more general and more representative of the concepts they stand for, than the commonly used/referenced measures originally proposed by Wagner. Further, a versatile digital modeling approach (BNK) is proposed that is inspired by NK systems. However, unlike NK systems, BNK incorporates a genotype and a phenotype, in addition to fitness. We develop and apply an Evolutionary Algorithm to a BNK-modeled system to find different types of perfect oscillators. We then map the resulting oscillating systems to possible genetic circuit realizations. Continuing with the synthetic biology theme, we also investigate the effect of noise in DNA synthesis on the predicted functionality of a DNA-based biosensor (i.e., its robustness), and we carry out a theoretical assessment of the evolvability of different types of ribozymes, undergoing directed evolution.

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Introduction: Visceral leishmaniasis (VL) is an important tropical and neglected disease and represents a serious global health problem. The initial interaction between the phagocytes and the parasite is crucial to determine the pathogen's capacity to initiate infection and it shapes the subsequent immune response that will develop. While type-1 T-cells induce IL-6, IL-1ß, TNF-α, and IL-12 production by monocytes/macrophages to fight the infection, type-2 T-cells are associated with a regulatory phenotype (IL-10 and TGF-ß) and successful infection establishment. Recently, our group demonstrated the role of an important Th1/Th17 T-cell population, the mucosal-associated invariant T (MAIT) cells, in VL. MAIT cells can respond to L. infantum by producing TNF-α and IFN-γ upon MR1-dependent activation. Objective and methods: Here, we describe the impact of the MR1-blockage on L. infantum internalization on the functional profile of circulating neutrophils and monocytes as well as the impact of the MR1-blockage on the soluble mediator signatures of in vitro whole blood cultures. Results: Overall, our data showed that VL patients presents higher percentage of activated neutrophils than asymptomatic and non-infected controls. In addition, MR1 blockade led to lower TNF-α and TGF-ß production by non-activated neutrophils from asymptomatic individuals. Moreover, TNF-α and IL-10 production by monocytes was higher in VL patients. In the analysis of soluble mediators produced in vitro, MR1-blockade induced a decrease of IFN-γ and an increase of IL-10, IL-27 and IL-33 in the cell cultures of AS group, a cytokine pattern associated with type 2 deleterious response. Discussion and conclusion: These data corroborate the hypothesis that MR1-restricted responses are associated to a protective role during Leishmania infection.

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Feeding behavior is a complex physiological process regulated by the interplay between homeostatic and hedonic feeding circuits. Among the neural structures involved, the nucleus accumbens (NAc) has emerged as a pivotal region at the interface of these two circuits. The NAc comprises distinct subregions and in this review, we focus mainly on the NAc shell (NAcSh). Homeostatic feeding circuits, primarily found in the hypothalamus, ensure the organism's balance in energy and nutrient requirements. These circuits monitor peripheral signals, such as insulin, leptin, and ghrelin, and modulate satiety and hunger states. The NAcSh receives input from these homeostatic circuits, integrating information regarding the organism's metabolic needs. Conversely, so-called hedonic feeding circuits involve all other non-hunger and -satiety processes, i.e., the sensory information, associative learning, reward, motivation and pleasure associated with food consumption. The NAcSh is interconnected with hedonics-related structures like the ventral tegmental area and prefrontal cortex and plays a key role in encoding hedonic information related to palatable food seeking or consumption. In sum, the NAcSh acts as a crucial hub in feeding behavior, integrating signals from both homeostatic and hedonic circuits, to facilitate behavioral output via its downstream projections. Moreover, the NAcSh's involvement extends beyond simple integration, as it directly impacts actions related to food consumption. In this review, we first focus on delineating the inputs targeting the NAcSh; we then present NAcSh output projections to downstream structures. Finally we discuss how the NAcSh regulates feeding behavior and can be seen as a neural hub integrating homeostatic and hedonic feeding signals, via a functionally diverse set of projection neuron subpopulations.

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Manufacturing of copper micro-patterns is crucial in electronics for its utilization as high conductivity transparent conductive films (TCFs) and circuits. In the preparation process of current TCFs, a plethora of materials have emerged that can replace traditional indium tin oxide (ITO). However, even for the most promising metal-based nanowire materials, there are issues such as high cost, complex welding, and high contact resistance. To address these problems, this paper proposes a printable and filament-drawable polydimethylsiloxane (PDMS)-based adhesive, which, through a novel additive patterning technology, efficiently and economically manufactures self-welding copper micro-meshes and circuits. The adhesive can be processed into micro-patterns through printing and filament drawing, on which ionic Ag can be in situ reduced and anchored, thereby eliminating the need for tedious pre- and post-treatment steps. The fully exposed Ag particles dramatically minimize the usage of precious metal catalyst, thus efficiently catalyzing electroless copper deposition (ECD) reaction. Highly conductive (1.03 × 107 S m-1) copper circuits can be fabricated on the printed adhesive patterns, exhibiting versatile applicability to diverse substrates. Highly precise copper micro-meshes (∼50 µm) can be fabricated on the filament networks drawn by the adhesive. The copper meshes undergo complete self-welding at junctions during the ECD process, thus exhibiting ultra-low square resistance of 0.45 Ω sq-1 while maintaining a high transmittance of 82.2 %. This is far superior to most of TCFs in published literature.

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BACKGROUND: Migraine is a neurological disorder characterized by complex, widespread, and sudden attacks with an unclear pathogenesis, particularly in chronic migraine (CM). Specific brain regions, including the insula, amygdala, thalamus, and cingulate, medial prefrontal, and anterior cingulate cortex, are commonly activated by pain stimuli in patients with CM and animal models. This study employs fluorescence microscopy optical sectioning tomography (fMOST) technology and AAV-PHP.eB whole-brain expression to map activation patterns of brain regions in CM mice, thus enhancing the understanding of CM pathogenesis and suggesting potential treatment targets. METHODS: By repeatedly administering nitroglycerin (NTG) to induce migraine-like pain in mice, a chronic migraine model (CMM) was established. Olcegepant (OLC) was then used as treatment and its effects on mechanical pain hypersensitivity and brain region activation were observed. All mice underwent mechanical withdrawal threshold, light-aversive, and elevated plus maze tests. Viral injections were administered to the mice one month prior to modelling, and brain samples were collected 2 h after the final NTG/vehicle control injection for whole-brain imaging using fMOST. RESULTS: In the NTG-induced CMM, mechanical pain threshold decreased, photophobia, and anxiety-like behavior were observed, and OLC was found to improve these manifestations. fMOST whole-brain imaging results suggest that the isocortex-cerebral cortex plate region, including somatomotor areas (MO), somatosensory areas (SS), and main olfactory bulb (MOB), appears to be the most sensitive area of activation in CM (P < 0.05). Other brain regions such as the inferior colliculus (IC) and intermediate reticular nucleus (IRN) were also exhibited significant activation (P < 0.05). The improvement in migraine-like symptoms observed with OLC treatment may be related to its effects on these brain regions, particularly SS, MO, ansiform lobule (AN), IC, spinal nucleus of the trigeminal, caudal part (Sp5c), IRN, and parvicellular reticular nucleus (PARN) (P < 0.05). CONCLUSIONS: fMOST whole-brain imaging reveals c-Fos + cells in numerous brain regions. OLC improves migraine-like symptoms by modulating brain activity in some brain regions. This study demonstrates the activation of the specific brain areas in NTG-induced CMM and suggests some regions as a potential treatment mechanism according to OLC.

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