Focal cortical dysplasia type II (FCDII) is a sporadic developmental malformation of the cerebral cortex characterized by dysmorphic neurons, dyslamination and medically refractory epilepsy. It has ...been hypothesized that FCD is caused by somatic mutations in affected regions. Here, we used deep whole-exome sequencing (read depth, 412-668×) validated by site-specific amplicon sequencing (100-347,499×) in paired brain-blood DNA from four subjects with FCDII and uncovered a de novo brain somatic mutation, mechanistic target of rapamycin (MTOR) c.7280T>C (p.Leu2427Pro) in two subjects. Deep sequencing of the MTOR gene in an additional 73 subjects with FCDII using hybrid capture and PCR amplicon sequencing identified eight different somatic missense mutations found in multiple brain tissue samples of ten subjects. The identified mutations accounted for 15.6% of all subjects with FCDII studied (12 of 77). The identified mutations induced the hyperactivation of mTOR kinase. Focal cortical expression of mutant MTOR by in utero electroporation in mice was sufficient to disrupt neuronal migration and cause spontaneous seizures and cytomegalic neurons. Inhibition of mTOR with rapamycin suppressed cytomegalic neurons and epileptic seizures. This study provides, to our knowledge, the first evidence that brain somatic activating mutations in MTOR cause FCD and identifies mTOR as a treatment target for intractable epilepsy in FCD.
We fabricated Cu2ZnSnS4 (CZTS) thin films through sulfurization of stacked metallic films. Three types of Cu-Zn-Sn metallic films, i.e., Cu-rich, Cu-correct and Cu-poor precursor films were sputtered ...onto Mo-coated glass. The sulfurization of stacked Cu-Zn-Sn alloy films was performed at a relatively high temperature, 570C, with S-powder evaporation. CZTS films from Cu-rich and Cu-correct precursors showed a Cu sub(2-x)S phase on the film surface, while CZTS films from Cu-poor precursors didn't show the Cu sub(2-x)S phase. However, all films didn't exhibit any extra secondary phase and exhibited good crystalline textures even with Cu-ratio differences in metallic precursor films. Fabricated CZTS films were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), and Raman scattering measurements. SEM cross-section images of CZTS films showed that Cu-poor CZTS films were grown with more smooth film surface compared with other types of CZTS films.
Abstract
For kesterite copper zinc tin sulfide/selenide (CZTSSe) solar cells to enter the market, in addition to efficiency improvements, the technological capability to produce flexible and ...large-area modules with homogeneous properties is necessary. Here, we report a greater than 10% efficiency for a cell area of approximately 0.5 cm
2
and a greater than 8% efficiency for a cell area larger than 2 cm
2
of certified flexible CZTSSe solar cells. By designing a thin and multi-layered precursor structure, the formation of defects and defect clusters, particularly tin-related donor defects, is controlled, and the open circuit voltage value is enhanced. Using statistical analysis, we verify that the cell-to-cell and within-cell uniformity characteristics are improved. This study reports the highest efficiency so far for flexible CZTSSe solar cells with small and large areas. These results also present methods for improving the efficiency and enlarging the cell area.
Focal cortical dysplasia (FCD) is a major cause of the sporadic form of intractable focal epilepsies that require surgical treatment. It has recently been reported that brain somatic mutations in ...MTOR account for 15%–25% of FCD type II (FCDII), characterized by cortical dyslamination and dysmorphic neurons. However, the genetic etiologies of FCDII-affected individuals who lack the MTOR mutation remain unclear. Here, we performed deep hybrid capture and amplicon sequencing (read depth of 100×–20,012×) of five important mTOR pathway genes—PIK3CA, PIK3R2, AKT3, TSC1, and TSC2—by using paired brain and saliva samples from 40 FCDII individuals negative for MTOR mutations. We found that 5 of 40 individuals (12.5%) had brain somatic mutations in TSC1 (c.64C>T p.Arg22Trp and c.610C>T p.Arg204Cys) and TSC2 (c.4639G>A p.Val1547Ile), and these results were reproducible on two different sequencing platforms. All identified mutations induced hyperactivation of the mTOR pathway by disrupting the formation or function of the TSC1-TSC2 complex. Furthermore, in utero CRISPR-Cas9-mediated genome editing of Tsc1 or Tsc2 induced the development of spontaneous behavioral seizures, as well as cytomegalic neurons and cortical dyslamination. These results show that brain somatic mutations in TSC1 and TSC2 cause FCD and that in utero application of the CRISPR-Cas9 system is useful for generating neurodevelopmental disease models of somatic mutations in the brain.
In the context of population aging, advances in healthcare technology, and growing interest in healthy aging and higher quality of life (QOL), have gained central focus in public health, particularly ...among middle-aged adults.
This study presented an optimal prediction model for QOL among middle-aged South Korean adults (N = 4,048; aged 30-55 years) using a machine-learning technique. Community-based South Korean population data were sampled through multistage stratified cluster sampling. Twenty-one variables related to individual factors and various lifestyle patterns were surveyed. QOL was assessed using the Short Form Health Survey (SF-12) and categorized into total QOL, physical component score (PCS), and mental component score (MCS). Seven machine-learning algorithms were used to predict QOL: decision tree, Gaussian Naïve Bayes, k-nearest neighbor, logistic regression, extreme gradient boosting, random forest, and support vector machine. Data imbalance was resolved with the synthetic minority oversampling technique (SMOTE). Random forest was used to compare feature importance and visualize the importance of each variable.
For predicting QOL deterioration, the random forest method showed the highest performance. The random forest algorithm using SMOTE showed the highest area under the receiver operating characteristic (AUC) for total QOL (0.822), PCS (0.770), and MCS (0.786). Applying the data, SMOTE enhanced model performance by up to 0.111 AUC. Although feature importance differed across the three QOL indices, stress and sleep quality were identified as the most potent predictors of QOL. Random forest generated the most accurate prediction of QOL among middle-aged adults; the model showed that stress and sleep quality management were essential for improving QOL.
The results highlighted the need to develop a health management program for middle-aged adults that enables multidisciplinary management of QOL.
Cd-free kesterite-based Cu2ZnSnSe4 (CZTSe)/In2S3 champion solar cell of 5.74% efficiency has been fabricated by chemical spray pyrolysis. In this fabrication route, CZTSe absorber layer was sprayed ...by using a precursor solution, where metallic salts were dissolved in water-based solvent and subsequently selenized with Se powder at high temperature. In2S3 buffer as an alternative to CdS buffer was also deposited by chemical spray pyrolysis. The device characteristics were studied by measuring dark/light illuminated J–V–T, external quantum efficiency, temperature dependence of open circuit voltage (V OC) and series resistance (R s), and admittance spectroscopy. The performance of sprayed CZTSe/In2S3 solar cell was found to be limited by high back-contact barrier potential, poor carrier collection, and detrimental intrinsic defect states in device.
The reliability and safety of advanced driver assistance systems and autonomous vehicles are highly dependent on the accuracy of automotive sensors such as radar, lidar, and camera. However, these ...sensors can be misaligned compared to the initial installation state due to external shocks, and it can cause deterioration of their performance. In the case of the radar sensor, when the mounting angle is distorted and the sensor tilt toward the ground or sky, the sensing performance deteriorates significantly. Therefore, to guarantee stable detection performance of the sensors and driver safety, a method for determining the misalignment of these sensors is required. In this paper, we propose a method for estimating the vertical tilt angle of the radar sensor using a deep neural network (DNN) classifier. Using the proposed method, the mounting state of the radar can be easily estimated without physically removing the bumper. First, to identify the characteristics of the received signal according to the radar misalignment states, radar data are obtained at various tilt angles and distances. Then, we extract range profiles from the received signals and design a DNN-based estimator using the profiles as input. The proposed angle estimator determines the tilt angle of the radar sensor regardless of the measured distance. The average estimation accuracy of the proposed DNN-based classifier is over 99.08%. Therefore, through the proposed method of indirectly determining the radar misalignment, maintenance of the vehicle radar sensor can be easily performed.
We present a simple and rapid method to isolate extracellular vesicles (EVs) by using a polyethylene glycol/dextran aqueous two-phase system (ATPS). This system isolated more than ~75% of ...melanoma-derived EVs from a mixture of EVs and serum proteins. To increase the purity of EVs, a batch procedure was combined as additional steps to remove protein contaminants, and removed more than ~95% of the protein contaminants. We also performed RT-PCR and western blotting to verify the diagnostic applicability of the isolated EVs, and detected mRNA derived from melanoma cells and CD81 in isolated EVs.
The impacts of Ge alloying on crystal growth and device properties of kesterite-based CZTSSe thin film solar cells fabricated by chalcogenization of sputtered stacks in S/Se ambient were ...investigated. It was found that Ge-alloyed CZTSSe material improved the grain growth, compactness of film texture, and crystallinity of absorber layers as a consequence of the device efficiencies were enhanced from ∼3 to 6%. The investigations on optoelectronic characteristics of devices illustrated that the improvements in devices were mainly governed by decrease in diode ideality factor, suppression of crossover effect between white and dark J–V curves, and reduction of defect level in Ge-alloyed CZTSSe solar cell device. These results suggest the possibility to achieve a further improvement in the optoelectronic characteristics of the devices that could be accomplished by optimization of the technological processes with a fine-tuning of the Ge content in the layers.
The defects states and carrier density of CZTSe absorber layers are two of the crucial factors that decide the photovoltaic performance of CZTSe thin film solar cells. Fine tailoring the defects and ...carrier density is a key to push the power conversion efficiency of CZTSe solar cells to a more competitive level. In this work, the phase properties, defect states, and carrier density of CZTSe thin film are well controlled by fine tuning the ratio of Zn/Sn in the range from 0.75 to 1.27. Capacity-Voltage measurements and Admittance Spectroscopy are used to characterize the carrier density, depletion region width, and defect states of the CZTSe solar cells. The results indicate that the defects states and carrier density of CZTSe layer are very sensitive to the ratio of Zn/Sn. Combining experimental results and numerical simulation, the statistic regularities of the photovoltaic parameters of the CZTSe solar cells with different ratios of Zn/Sn is well explained. The increase of VOC of CZTSe solar cells with the ratio of Zn/Sn is related to both the increased carrier density and the decreased deep level defects states. The decline of JSC of the Zn-rich solar cells is caused by both the shrunken depletion region width and a large barrier caused by ZnSe phase. This barrier is the cause for a low fill factor in the Zn-rich solar cells. Overall, the CZTSe solar cells with a stoichiometric ratio of Zn/Sn=1.02 have favorable defects property and carrier density, thus resulting in the highest photovoltaic efficiency of 10.21%.
Display omitted
•The defects and carrier density can be tailored by fine tuning the ratio of Zn/Sn.•The carrier density of CZTSe solar cells increases with the ratio of Zn/Sn.•High density of deep level defects exists in Zn-poor CZTSe solar cells.•The optimal ratio of Zn/Sn for CZTSe solar cells is close to 1.0.•The best CZTSe solar cell achieves 10.2% efficiency with Zn/Sn=1.02.
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