Structural cracks are a vital feature in evaluating the health of aging structures. Inspectors regularly monitor structures' health using visual information because early detection of cracks on ...highly trafficked structures is critical for maintaining the public's safety. In this work, a framework for detecting cracks along with their locations is proposed. Image data provided by an unmanned aerial vehicle (UAV) is stitched using image processing techniques to overcome limitations in the resolution of cameras. This stitched image is analyzed to identify cracks using a deep learning model that makes judgements regarding the presence of cracks in the image. Moreover, cracks' locations are determined using data from UAV sensors. To validate the system, cracks forming on an actual building are captured by a UAV, and these images are analyzed to detect and locate cracks. The proposed framework is proven as an effective way to detect cracks and to represent the cracks' locations.
An accurate and reliable positioning system (PS) is a significant topic of research due to its broad range of aerospace applications, such as the localization of autonomous agents in GPS-denied and ...indoor environments. The PS discussed in this work uses ultra-wide band (UWB) sensors to provide distance measurements. UWB sensors are based on radio frequency technology and offer low power consumption, wide bandwidth, and precise ranging in the presence of nominal environmental noise. However, in practical situations, UWB sensors experience varying measurement noise due to unexpected obstacles in the environment. The localization accuracy is highly dependent on the filtering of such noise, and the extended Kalman filter (EKF) is one of the widely used techniques. In varying noise situations, where the obstacles generate larger measurement noise than nominal levels, EKF cannot offer precise results. Therefore, this work proposes two approaches based on EKF: sequential adaptive EKF and piecewise adaptive EKF. Simulation studies are conducted in static, linear, and nonlinear scenarios, and it is observed that higher accuracy is achieved by applying the proposed approaches as compared to the traditional EKF method.
Heterozygous mutations in GBA, the gene encoding the lysosomal enzyme glucosylceramidase beta/β-glucocerebrosidase, comprise the most common genetic risk factor for Parkinson disease (PD), but the ...mechanisms underlying this association remain unclear. Here, we show that in Gba
L444P/WT
knockin mice, the L444P heterozygous Gba mutation triggers mitochondrial dysfunction by inhibiting autophagy and mitochondrial priming, two steps critical for the selective removal of dysfunctional mitochondria by autophagy, a process known as mitophagy. In SHSY-5Y neuroblastoma cells, the overexpression of L444P GBA impeded mitochondrial priming and autophagy induction when endogenous lysosomal GBA activity remained intact. By contrast, genetic depletion of GBA inhibited lysosomal clearance of autophagic cargo. The link between heterozygous GBA mutations and impaired mitophagy was corroborated in postmortem brain tissue from PD patients carrying heterozygous GBA mutations, where we found increased mitochondrial content, mitochondria oxidative stress and impaired autophagy. Our findings thus suggest a mechanistic basis for mitochondrial dysfunction associated with GBA heterozygous mutations.
Abbreviations: AMBRA1: autophagy/beclin 1 regulator 1; BECN1: beclin 1, autophagy related; BNIP3L/Nix: BCL2/adenovirus E1B interacting protein 3-like; CCCP: carbonyl cyanide 3-chloroyphenylhydrazone; CYCS: cytochrome c, somatic; DNM1L/DRP1: dynamin 1-like; ER: endoplasmic reticulum; GBA: glucosylceramidase beta; GBA-PD: Parkinson disease with heterozygous GBA mutations; GD: Gaucher disease; GFP: green fluorescent protein; LC3B: microtubule-associated protein 1 light chain 3 beta; LC3B-II: lipidated form of microtubule-associated protein 1 light chain 3 beta; MitoGreen: MitoTracker Green; MitoRed: MitoTracker Red; MMP: mitochondrial membrane potential; MTOR: mechanistic target of rapamycin kinase; MYC: MYC proto-oncogene, bHLH transcription factor; NBR1: NBR1, autophagy cargo receptor; Non-GBA-PD: Parkinson disease without GBA mutations; PD: Parkinson disease; PINK1: PTEN induced putative kinase 1; PRKN/PARK2: parkin RBR E3 ubiquitin protein ligase; RFP: red fluorescent protein; ROS: reactive oxygen species; SNCA: synuclein alpha; SQSTM1/p62: sequestosome 1; TIMM23: translocase of inner mitochondrial membrane 23; TOMM20: translocase of outer mitochondrial membrane 20; VDAC1/Porin: voltage dependent anion channel 1; WT: wild type
Recent advances in 3D culture systems have led to the generation of brain organoids that resemble different human brain regions; however, a 3D organoid model of the midbrain containing functional ...midbrain dopaminergic (mDA) neurons has not been reported. We developed a method to differentiate human pluripotent stem cells into a large multicellular organoid-like structure that contains distinct layers of neuronal cells expressing characteristic markers of human midbrain. Importantly, we detected electrically active and functionally mature mDA neurons and dopamine production in our 3D midbrain-like organoids (MLOs). In contrast to human mDA neurons generated using 2D methods or MLOs generated from mouse embryonic stem cells, our human MLOs produced neuromelanin-like granules that were structurally similar to those isolated from human substantia nigra tissues. Thus our MLOs bearing features of the human midbrain may provide a tractable in vitro system to study the human midbrain and its related diseases.
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•Self-organizing midbrain-like organoids (hMLOs) develop from hPSCs in 3D culture•hMLOs, but not mouse MLOs or human cerebral organoids, produce neuromelanin•hMLOs secrete dopamine (DA) and neurons within the hMLOs form functional synapses•Neurons within hMLOs exhibit SNpc DA neuron-like electrophysiological properties
Jo et al. report a method for generating human midbrain-like organoids (hMLOs) from hPSCs in 3D culture. The hMLOs contain distinct layers of neuronal cells expressing human midbrain markers, such as neuromelanin, are electrically active, form functional synapses, and produce dopamine, suggesting that they may be useful for studying human midbrain.
The development of implantable neuroelectrodes is advancing rapidly as these tools are becoming increasingly ubiquitous in clinical practice, especially for the treatment of traumatic and ...neurodegenerative disorders. Electrodes have been exploited in a wide number of neural interface devices, such as deep brain stimulation, which is one of the most successful therapies with proven efficacy in the treatment of diseases like Parkinson or epilepsy. However, one of the main caveats related to the clinical application of electrodes is the nervous tissue response at the injury site, characterized by a cascade of inflammatory events, which culminate in chronic inflammation, and, in turn, result in the failure of the implant over extended periods of time. To overcome current limitations of the most widespread macroelectrode based systems, new design strategies and the development of innovative materials with superior biocompatibility characteristics are currently being investigated. This review describes the current state of the art of
, and
models available for the study of neural tissue response to implantable microelectrodes. We particularly highlight new models with increased complexity that closely mimic
scenarios and that can serve as promising alternatives to animal studies for investigation of microelectrodes in neural tissues. Additionally, we also express our view on the impact of the progress in the field of neural tissue engineering on neural implant research.
Neuromorphic computing, an alternative for von Neumann architecture, requires synapse devices where the data can be stored and computed in the same place. The three-terminal synapse device is ...attractive for neuromorphic computing due to its high stability and controllability. However, high nonlinearity on weight update, low dynamic range, and incompatibility with conventional CMOS systems have been reported as obstacles for large-scale crossbar arrays. Here, we propose the CMOS compatible gate injection-based field-effect transistor employing thermionic emission to enhance the linear conductance update. The dependence of the linearity on the conduction mechanism is examined by inserting an interfacial layer in the gate stack. To demonstrate the conduction mechanism, the gate current measurement is conducted under varying temperatures. The device based on thermionic emission achieves superior synaptic characteristics, leading to high performance on the artificial neural network simulation as 93.17% on the MNIST dataset.
In this study, we investigate what drives the MAX effect in the South Korean stock market. We find that the MAX effect is significant only for overpriced stocks categorized by the composite ...mispricing index. Our results suggest that investors' demand for the lottery and the arbitrage risk effect of MAX may overlap and negate each other. Furthermore, MAX itself has independent information apart from idiosyncratic volatility (IVOL), which assures that the high positive correlation between IVOL and MAX does not directly cause our empirical findings. Finally, by analyzing the direct trading behavior of investors, our results suggest that investors' buying pressure for lottery-like stocks is concentrated among overpriced stocks.
We have previously reported that NADPH oxidase 2 (Nox2) is up-regulated in spinal cord microglia after spinal nerve injury, demonstrating that it is critical for microglia activation and subsequent ...pain hypersensitivity. However, the mechanisms and molecules involved in Nox2 induction have not been elucidated. Previous studies have shown that Toll-like receptors (TLRs) are involved in nerve injury-induced spinal cord microglia activation. In this study, we investigated the role of TLR in Nox2 expression in spinal cord microglia after peripheral nerve injury. Studies using TLR knock-out mice have shown that nerve injury-induced microglial Nox2 up-regulation is abrogated in TLR2 but not in TLR3 or -4 knock-out mice. Intrathecal injection of lipoteichoic acid, a TLR2 agonist, induced Nox2 expression in spinal cord microglia both at the mRNA and protein levels. Similarly, lipoteichoic acid stimulation induced Nox2 expression and reactive oxygen species production in primary spinal cord glial cells in vitro. Studies on intracellular signaling pathways indicate that NF-κB and p38 MAP kinase activation is required for TLR2-induced Nox2 expression in glial cells. Conclusively, our data show that TLR2 mediates nerve injury-induced Nox2 gene expression in spinal cord microglia via NF-κB and p38 activation and thereby may contribute to spinal cord microglia activation.
Background: Microglial NADPH oxidase 2 (Nox2) expression is critical for nerve injury-induced spinal cord microglia activation and subsequent pain hypersensitivity.
Results: Toll-like receptor 2 (TLR2) is required for Nox2 expression in spinal cord microglia after spinal nerve injury.
Conclusion: TLR2 signaling mediates nerve injury-induced Nox2 expression in spinal cord microglia.
Significance: Targeting TLR2-Nox2 pathway may be a new option for preventing neuropathic pain.
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