Extrachromosomal telomere DNA derived from excessive strand displacements.

Alternative lengthening of telomeres (ALT) is a telomere maintenance mechanism mediated by break-induced replication, evident in approximately 15% of human cancers. A characteristic feature of ALT cancers is the presence of C-circles, circular single-stranded telomeric DNAs composed of C-rich sequences. Despite the fact that extrachromosomal C-rich single-stranded DNAs (ssDNAs), including C-circles, are unique to ALT cells, their generation process remains undefined. Here, we introduce a method to detect single-stranded telomeric DNA, called 4SET (Strand-Specific Southern-blot for Single-stranded Extrachromosomal Telomeres) assay. Utilizing 4SET, we are able to capture C-rich single-stranded DNAs that are near 200 to 1500 nucleotides in size. Both linear C-rich ssDNAs and C-circles are abundant in the fractions of cytoplasm and nucleoplasm, which supports the idea that linear and circular C-rich ssDNAs are generated concurrently. We also found that C-rich ssDNAs originate during Okazaki fragment processing during lagging strand DNA synthesis. The generation of C-rich ssDNA requires CST-PP (CTC1/STN1/TEN1-PRIMASE-Polymerase alpha) complex-mediated priming of the C-strand DNA synthesis and subsequent excessive strand displacement of the C-rich strand mediated by the DNA Polymerase delta and the BLM helicase. Our work proposes a model for the generation of C-rich ssDNAs and C-circles during ALT-mediated telomere elongation.

Deregulated DNA ADP-ribosylation impairs telomere replication.

The recognition that DNA can be ADP ribosylated provides an unexpected regulatory level of how ADP-ribosylation contributes to genome stability, epigenetics and immunity. Yet, it remains unknown whether DNA ADP-ribosylation (DNA-ADPr) promotes genome stability and how it is regulated. Here, we show that telomeres are subject to DNA-ADPr catalyzed by PARP1 and removed by TARG1. Mechanistically, we show that DNA-ADPr is coupled to lagging telomere DNA strand synthesis, forming at single-stranded DNA present at unligated Okazaki fragments and on the 3' single-stranded telomere overhang. Persistent DNA-linked ADPr, due to TARG1 deficiency, eventually leads to telomere shortening. Furthermore, using the bacterial DNA ADP-ribosyl-transferase toxin to modify DNA at telomeres directly, we demonstrate that unhydrolyzed DNA-linked ADP-ribose compromises telomere replication and telomere integrity. Thus, by identifying telomeres as chromosomal targets of PARP1 and TARG1-regulated DNA-ADPr, whose deregulation compromises telomere replication and integrity, our study highlights and establishes the critical importance of controlling DNA-ADPr turnover for sustained genome stability.

Choroidal manifestations of non-ocular sarcoidosis: an enhanced depth imaging OCT study.

BACKGROUND: Although choroidal thickening was reported as a sign of active inflammation in ocular sarcoidosis, there has been no research on the choroidal changes in non-ocular sarcoidosis (defined as systemic sarcoidosis without overt clinical signs of ocular involvement). Therefore, this study aimed to investigate choroidal structural changes in patients with non-ocular sarcoidosis. METHODS: This retrospective case-control study was conducted at Asan Medical Center, a tertiary referral center. We evaluated 30 eyes with non-ocular sarcoidosis and their age- and spherical equivalent-matched healthy control eyes. The subfoveal choroidal thickness, area ratio (Sattler layer-choriocapillaris complex [SLCC] area to Haller layer [HL] area), and choroidal vascularity index (CVI, luminal area to choroidal area) were analyzed using enhanced depth imaging in optical coherence tomography. Systemic and ocular factors associated with the choroidal thickness were investigated. RESULTS: Compared with the healthy control group, the non-ocular sarcoidosis group had significantly thicker subfoveal choroid (total and all sublayers [SLCC and HL]) and lower area ratio. There were no significant differences in the CVIs at all sublayers between groups. In the non-ocular sarcoidosis group, eyes under oral steroid treatment had thinner choroid than eyes under observation. In the control group, eyes with older age and more myopic spherical equivalent had thinner choroidal thickness. CONCLUSION: Total and all sublayers of the subfoveal choroid were significantly thicker without significant vascularity changes in non-ocular sarcoidosis eyes than in healthy control eyes. The degree of choroidal thickening was disproportionally greater at HL than at SLCC. These characteristic choroidal changes may be the subclinical manifestations in non-ocular sarcoidosis.

From Homogeneity to Turing Pattern: Kinetically Controlled Self-Organization of Transmembrane Protein.

Understanding the spatial organization of membrane proteins is crucial for unraveling key principles in cell biology. The reaction-diffusion model is commonly used to understand biochemical patterning; however, applying reaction-diffusion models to subcellular phenomena is challenging because of the difficulty in measuring protein diffusivity and interaction kinetics in the living cell. In this work, we investigated the self-organization of the plasmalemma vesicle-associated protein (PLVAP), which creates regular arrangements of fenestrated ultrastructures, using single-molecule tracking. We demonstrated that the spatial organization of the ultrastructures is associated with a decrease in the association rate by actin destabilization. We also constructed a reaction-diffusion model that accurately generates a hexagonal array with the same 130 nm spacing as the actual scale and informs the stoichiometry of the ultrastructure, which can be discerned only through electron microscopy. Through this study, we integrated single-molecule experiments and reaction-diffusion modeling to surpass the limitations of static imaging tools and proposed emergent properties of the PLVAP ultrastructure.

Clinical manifestations and associated factors of uveitis in patients with pulmonary sarcoidosis: a case control study.

Sarcoidosis, an idiopathic and inflammatory disease, affects various organs and can manifest as uveitis. Due to limited evidence, researchers investigated the risk factors associated with uveitis in patients with pulmonary sarcoidosis. A retrospective study was conducted on 71 pulmonary sarcoidosis patients, including 19 with uveitis and 52 without. Data on involved organs, imaging findings, spirometry, and analyses from blood and bronchoalveolar lavage fluid were collected. Logistic regression models were used for multivariate analysis. Among the 71 newly diagnosed pulmonary sarcoidosis patients, uveitis was observed in 19 patients (26.8%). No significant differences were found in clinical characteristics between patients with and without uveitis. Fewer patients with uveitis presented lung parenchymal lesions (P = 0.043). In multivariate analysis, skin lesions (aOR 7.619, 95% CI 1.277-45.472, P = 0.026) and ophthalmic symptoms (aOR 4.065, 95% CI 1.192-13.863, P = 0.025) were associated with uveitis. Absence of uveitis was related to lung parenchymal lesions (aOR 0.233, 95% CI 0.062-0.883, P = 0.032). Approximately one-quarter of patients with an initial diagnosis of pulmonary sarcoidosis were diagnosed with uveitis. Presence of skin lesions, ophthalmic symptoms, and absence of lung parenchymal lesions were related to uveitis. These results need to be clarified by further studies to confirm the clinical role of early ophthalmologic screening for pulmonary sarcoidosis patients with these factors.

Extrachromosomal Telomeres Derived from Excessive Strand Displacements.

Alternative Lengthening of Telomeres (ALT) is a telomere maintenance mechanism mediated by break-induced replication (BIR), evident in approximately 15% of human cancers. A characteristic feature of ALT cancers is the presence of C-circles, circular single-stranded telomeric DNAs composed of C-rich sequences. Despite the fact that extrachromosomal C-rich single-stranded DNAs (ssDNAs), unique to ALT cells, are considered potential precursors of C-circles, their generation process remains undefined. Here, we introduce a highly sensitive method to detect single stranded telomeric DNA, called 4SET (Strand-Specific Southern-blot for Single-stranded Extrachromosomal Telomeres) assay. Utilizing 4SET, we are able to capture C-rich single stranded DNAs that are near 200 to 1500 nucleotides in size. Both linear C-rich ssDNAs and C-circles are abundant in the fractions of cytoplasm and nucleoplasm, which supports the idea that linear C-rich ssDNA accumulation may indeed precede C-circle formation. We also found that C-rich ssDNAs originate during Okazaki fragment processing during lagging strand DNA synthesis. The generation of C-rich ssDNA requires CST-PP (CTC1/STN1/TEN1-PRIMASE-Polymerase alpha) complex-mediated priming of the C-strand DNA synthesis and subsequent excessive strand displacement of the C-rich strand mediated by the DNA Polymerase delta and the BLM helicase. Our work proposes a new model for the generation of C-rich ssDNAs and C-circles during ALT-mediated telomere elongation.

Exosomal miR-184 in the aqueous humor of patients with central serous chorioretinopathy: a potential diagnostic and prognostic biomarker.

BACKGROUND: Central serous chorioretinopathy (CSC) is the fourth most prevalent retinal disease leading to age-related macular degeneration (AMD) and retinal atrophy. However, CSC's pathogenesis and therapeutic target need to be better understood. RESULTS: We investigated exosomal microRNA in the aqueous humor of CSC patients using next-generation sequencing (NGS) to identify potential biomarkers associated with CSC pathogenesis. Bioinformatic evaluations and NGS were performed on exosomal miRNAs obtained from AH samples of 62 eyes (42 CSC and 20 controls). For subgroup analysis, patients were divided into treatment responders (CSC-R, 17 eyes) and non-responders (CSC-NR, 25 eyes). To validate the functions of miRNA in CECs, primary cultured-human choroidal endothelial cells (hCEC) of the donor eyes were utilized for in vitro assays. NGS detected 376 miRNAs. Our results showed that patients with CSC had 12 significantly upregulated and 17 downregulated miRNAs compared to controls. miR-184 was significantly upregulated in CSC-R and CSC-NR patients compared to controls and higher in CSC-NR than CSC-R. In vitro assays using primary cultured-human choroidal endothelial cells (hCEC) demonstrated that miR-184 suppressed the proliferation and migration of hCECs. STC2 was identified as a strong candidate for the posttranscriptional down-regulated target gene of miR-184. CONCLUSION: Our findings suggest that exosomal miR-184 may serve as a biomarker reflecting the angiostatic capacity of CEC in patients with CSC.

Real-world study to evaluate the efficacy and safety of intravitreal brolucizumab for refractory neovascular age-related macular degeneration.

This retrospective study evaluated the real-world safety and effectiveness of switching to intravitreal brolucizumab for refractory neovascular age-related macular degeneration (nAMD). A total of 81 patients who received brolucizumab injections as switch therapy were followed for more than 3 months. A good response was defined as better anatomical improvement or extended injection intervals compared with previous anti-vascular endothelial growth factor (VEGF) treatment over a mean follow-up period of 41.4 weeks. Approximately 82.7% of patients showed a good response after switching. After 1 year, patients showed significant visual gains (+ 6.6 letters, p = 0.006) and central retinal thickness reductions (- 112.6 µm, p < 0.001), with 30.8% having injection intervals extended over 12 weeks. In the poor-response group, visual acuity and anatomical outcomes worsened soon after switching. More previous injections, thinner baseline central retina, and the presence of prechoroidal cleft or polypoidal lesion resulted in a better response (p < 0.05). Adverse effects occurred in eight eyes (9.9%), including one retinal vascular occlusion and seven intraocular inflammation cases, which were unrelated to the response. Most patients with nAMD refractory to anti-VEGF treatment demonstrated anatomical improvement or extended injection intervals after switching. This study shows that identified structural biomarkers may predict treatment response and select an appropriate therapeutic strategy.

Factors Affecting Intensive Aflibercept Treatment Response in Diabetic Macular Edema: A Real-World Study.

Objective: To investigate the systemic and ocular factors that affect the response to intensive aflibercept treatment in diabetic macular edema (DME) in a real-world setting. Methods: This retrospective cohort study evaluated 30 eyes of 23 patients with DME who underwent intensive intravitreal aflibercept injections (five monthly loading doses). Treatment response was assessed by central retinal thickness (CRT) and best-corrected visual acuity (BCVA) at each monthly visit. The patients were categorized as good (<300 µm) and suboptimal (≥300 µm) responders based on CRT after the loading phase. Baseline systemic and ocular factors associated with treatment response were investigated. Results: The mean CRT and BCVA significantly improved after five loading injections (486.87 ± 95.46 to 334.90 ± 69.47 µm and 0.51 ± 0.30 to 0.35 ± 0.25 LogMAR, respectively, all p < 0.05). During 12 months of follow-up, 16 eyes (53.33%) maintained CRT without additional treatment. Eyes with diabetes mellitus (DM) for ≥15 years, estimated glomerular filtration rate (eGFR) < 80 mL/min/1.73 m2, serum creatinine ≥ 0.95 mg/dL and potassium ≥ 4.7 mmol/L, and presence of epiretinal membrane (ERM) were more likely to have a suboptimal response to the treatment. Conclusions: Five monthly loading doses of intravitreal aflibercept injection provided significant anatomical and visual improvements in patients with DME. Patients with longer DM duration, lower eGFR, higher serum creatinine or potassium levels, or ERM were predisposed to a suboptimal treatment response. Individual response to intensive aflibercept treatment for DME can be predicted by these systemic and ocular risk factors.

Molecular, Cellular, and Functional Heterogeneity of Retinal and Choroidal Endothelial Cells.

Purpose: To investigate the endothelial heterogeneity across distinct vascular beds in the inner and outer blood-retinal barriers. Methods: We evaluated the molecular, cellular, and functional differences between primary human retinal endothelial cells (HRECs) and human choroidal endothelial cells (HCECs) in terms of angiogenic and vasculogenic properties, permeability, and transcytosis. Tube formation assay, cell migration assay, in vitro permeability assay, microfluidic sprouting assay, and transcriptome analysis were performed. Results: HRECs showed higher proliferation and migration activity than did HCECs, whereas the tube formation ability was similar between HRECs and HCECs. Under angiogenic stimuli, HCECs displayed earlier sprouting angiogenesis, but the overall speed was faster and more stable in HRECs. HRECs expressed higher levels of adherens junctional proteins, whereas the tight junctional genes and transcytosis-related genes were more highly expressed in HCECs. Angiopoietin-2 was predominantly expressed in HRECs, but vascular endothelial growth factor (VEGF) receptors were more strongly expressed in HCECs. Platelet-derived growth factor subunit B (PDGFB) was more highly expressed in HRECs, which correlates to the lower degree of pericyte coverage in choroidal blood vessels. Conclusions: Retinal and choroidal ECs showed significant cellular and molecular heterogeneities that correlated with their functional characteristics. Retinal ECs are vasculogenic with high migratory characteristics and faster angiogenic sprouting, and they are more responsive to VEGF-induced permeability. In contrast, choroidal ECs express high levels of transcytosis genes, and they are vasculogenic, rather proliferative, adept in generating tip cells, and less responsive to VEGF-induced permeability.

Lower skeletal muscle mass is associated with diabetes and insulin resistance: A cross-sectional study.

AIMS: The association between skeletal muscle mass and diabetes incidence/insulin resistance/glycated hemoglobin (HbA1C) is unknown. The aim of this study was to investigate such association in clinically apparently healthy males and females. METHODS: A cross-sectional study of 372,399 Korean males and females who completed bioelectrical impedance analysis (BIA) in a health-screening programme was performed. Skeletal muscle index was used as an indicator of skeletal muscle mass. Skeletal muscle index (%) [appendicular skeletal muscle mass (kg)/body weight (kg)X100] was estimated using BIA. The study outcomes were diabetes incidence, homoeostasis model assessment of insulin resistance (HOMA-IR), and HbA1C. RESULTS: The mean age of study participants was 38.92 ± 8.54 years. Multiple logistic regression analysis revealed a significant negative association between Skeletal muscle index and diabetes incidence/HOMA-IR/HbA1C after adjusting for various confounding factors. Odds ratios (95% confidence interval (CI)) of diabetes incidence in Q2, Q3, and Q4 compared to the lowest quantile (Q1) were 0.95 (0.85-1.05), 0.88 (0.78-0.99), and 0.79 (0.69-0.9), respectively. Beta coefficients (95% CI) of HOMA-IR in Q2, Q3, and Q3 with Q1 were 0.05 (0.03-0.07), -0.06 (-0.09∼-0.04), and -0.19 (-0.22∼-0.16), respectively. Beta coefficients (95% CI) of HbA1C in Q2, Q3, and Q4 with Q1 were 0.02 (0.01-0.03), -0.001 (-0.01∼0.01), and -0.02 (-0.03∼-0.01), respectively. CONCLUSIONS: This study demonstrated negative associations of skeletal muscle mass with diabetes incidence, insulin resistance, and HbA1C levels in healthy adults.

Relationship between rotator cuff posterior delamination and subscapularis tear: a large cross-sectional analysis.

Background: Rotator cuff posterior delamination and subscapularis tear are commonly observed in rotator cuff injuries. However, there are very few studies on the relationship between posterior delamination and subscapularis tendon tear. This study aimed to investigate the relationship between posterior delamination and subscapularis tendon tear. Methods: The study was conducted from March 2018 to June 2021 with 553 patients who underwent rotator cuff repairs at two institutions. The age and gender, size of rotator cuff tear, duration of symptoms, range of motion of shoulder joint, visual analog scale score, Korean Shoulder Scale score, gap and width of rotator cuff tear, and fatty degeneration of the supraspinatus and infraspinatus muscles were compared to confirm the differences between a delaminated and nondelaminated rotator cuff tear. Moreover, the proportions of the subscapular tendon rupture and subscapularis tendon rupture according to the size of the rotator cuff tear were analyzed in both the delaminated and nondelaminated rotator cuff tear groups. Results: Compared to the nondelaminated rotator cuff tear group, the age of the delaminated rotator cuff tear group was significantly higher, and as the size of the rotator cuff tear increased, the proportion of delaminated tear increased (P < .001). Furthermore, the duration of symptoms was longer, visual analog scale score was higher, Korean Shoulder Scale score was lower, gap and width of rotator cuff as well as fatty degeneration of the supraspinatus and infraspinatus were more severe in the group with posterior delamination than that without. In the nondelaminated rotator cuff tear group, 212 subjects (84.46%) had no subscapularis tear, and 39 subjects (15.54%) had subscapularis tear. In the delaminated rotator cuff tear group, 103 subjects (34.11%) had no subscapular tendon tear while 199 subjects (65.89%) had a subscapular tendon tear (P < .001). Furthermore, as the size of the rotator cuff tear increased, the rate of subscapular tendon tear increased in both the delaminated and nondelaminated rotator cuff tear groups. Conclusions: The results suggest that there is a high probability of concomitant rupture of the subscapularis tendon in the patient group with posterior delamination tear. Therefore, it should be noted that if a posterior delamination is confirmed during surgery, it is necessary to carefully check for rupture of the scapular tendon.

Design and Characteristic Analysis of an Axial Flux High-Temperature Superconducting Motor for Aircraft Propulsion.

In line with global environmental regulations, the demand for eco-friendly and highly efficient aircraft propulsion systems is increasing. The combination of axial flux motors and superconductors could be a key technology used to address these needs. In this paper, an axial flux high temperature superconducting (HTS) motor for aircraft propulsion was designed and its characteristics were analyzed. A 2G HTS wire with high magnetic flux characteristic was used for the field winding of the 120 kW axial flux HTS motor, and the rotational speed and rated voltage of the motor were 2000 rpm and 220 V, respectively. The axial flux HTS motor implements a revolving armature type for solid cooling of the HTS field coil. The electromagnetic and thermal features of the motor were analyzed and designed utilizing a 3D finite element method program. The HTS coil was maintained at the target temperature by effectively designing the current lead and cooling system to minimize heat loss. These results can be effectively used in the design of propulsion systems for large commercial aircraft in the future as well as for the design of small aircraft with less than 4 seats.

Qualitative and quantitative evaluation of diabetic choroidopathy using ultra-widefield indocyanine green angiography.

To investigate angiographic characteristic features of diabetic choroidopathy, as well as choroidal vascular density (CVD) and fractal dimension (CFD) in diabetic eyes and controls using ultra-widefield (UWF) indocyanine green angiography (ICGA). All patients underwent UWF fluorescein angiography and ICGA. Using imageJ software, CVD and CFD was analyzed. SFCT was assessed using spectral-domain optical coherence tomography. The image parameters were compared based on the DR stage and the presence of diabetic macular edema (DME). One-hundred six eyes from 63 patients (59.11 ± 16.31 years; male [%]: 23 [36.5%]) were included in the DM group, and 40 eyes from 22 subjects were included in the control group. The DM group had a mean age of 59.11 ± 16.31 years and a mean HbA1c percentage of 7.72 ± 1.28%. The most common ICGA findings of DC were choroidal hyperpermeability (57.5%), hypofluorescent spots (48.1%). Salt and pepper pattern (19.8%), inverted inflow phenomenon (3.8%), choroidal arterial tortuosity (24.5%), and late choroidal non-perfusion (6.6%) were more common in advanced DR. The CVD, CFD, and SFCT increased as the DR severity progressed. The DME group had a significantly higher CFD and SFCT than the non-DME group (P < 0.001 and P = 0.019, respectively). The qualitative and quantitative UWF ICGA image analysis revealed that choroidal blood vessels became dilated, complex, and hyperpermeable as the DR progressed. These features of diabetic choroidopathy (DC) were more severe in eyes with DME than the non-DME eyes.

Predictive factors for microvascular recovery after treatments for diabetic retinopathy.

BACKGROUND: To identify factors associated with microvascular recovery after intravitreal bevacizumab or panretinal photocoagulation (PRP) in diabetic retinopathy (DR). METHODS: We retrospectively reviewed 320 eyes/patients with DR treated with intravitreal bevacizumab and/or PRP. Two consecutive fluorescein angiographies (FAs) of each eye were compared. The number of microaneurysms and the area of capillary non-perfusion were calculated automatically using ImageJ software. Microvascular recovery was defined as a marked reduction in the numbers of microaneurysms (< 20%) or a marked reduction in the area of capillary non-perfusion (< 50%) in 45-degree fields or a complete regression of new vessels in ETDRS 7 standard fields. Baseline FA findings and changes in the ocular and systemic factors were analyzed. RESULTS: Twenty-eight (8.8%) of the 320 total eyes were found to meet the criteria of microvascular recovery after the treatments. Multivariate analysis revealed the presence of diffuse capillary telangiectasis (P = .003) and late disc leaking (P = .007) on baseline FA and a reduction of glycated hemoglobin (P = .005) during the follow-up period were predictive factors of microvascular recovery after the treatments. Although the microvascular recovery group presented with a significant improvement of BCVA after the treatments, the baseline BCVA could not predict the microvascular recovery after the treatments. CONCLUSIONS: Diffuse capillary telangiectasis or late disc leaking on baseline FA and improved glycemic control positively predicted the microvascular recovery after treatments for DR.

Associations between oral health status and risk of fractures in elder adults.

Oral health condition, bone mineral density, skeletal muscle mass, fall, fracture, and frailty seem to be strongly interconnected. This study aimed to investigate associations between probability of osteoporotic fractures and oral health in the elderly. In total, 2322 Korean subjects from the 2008-2009 Korea National Health and Nutritional Examination Survey aged over 65 years were included. The 10-year probabilities of major and hip fractures were calculated using the Fracture Risk Assessment (FRAX) tool. Data on anthropometry, skeletal bone mineral density, sociodemographic characteristics, physical activity, individual history of fractures and falls, parental history of osteoporosis, number of teeth, metabolic syndrome, the Decayed, Missing, and Filled permanent Teeth index, and Community Periodontal Index (CPI), were collected. Participants were classified into three groups based on FRAX score for major osteoporotic fractures. A multivariate linear regression analysis was conducted to analyze associations between FRAX scores and oral health-related factors, adjusting for confounding factors. BMI, presence of metabolic syndrome, number of teeth, dental patterns, and CPI score showed significant differences among three groups in males and females. Results from multivariate linear regression analysis demonstrated significant relationships between total tooth number and probabilities of fracture in male and female elderly. The interdisciplinary approach for handling osteoporosis and sarcopenia including dentists, physicians is necessary to facilitate a better quality of life in the elderly.

Cognitive Refined Augmentation for Video Anomaly Detection in Weak Supervision.

Weakly supervised video anomaly detection is a methodology that assesses anomaly levels in individual frames based on labeled video data. Anomaly scores are computed by evaluating the deviation of distances derived from frames in an unbiased state. Weakly supervised video anomaly detection encounters the formidable challenge of false alarms, stemming from various sources, with a major contributor being the inadequate reflection of frame labels during the learning process. Multiple instance learning has been a pivotal solution to this issue in previous studies, necessitating the identification of discernible features between abnormal and normal segments. Simultaneously, it is imperative to identify shared biases within the feature space and cultivate a representative model. In this study, we introduce a novel multiple instance learning framework anchored on a memory unit, which augments features based on memory and effectively bridges the gap between normal and abnormal instances. This augmentation is facilitated through the integration of an multi-head attention feature augmentation module and loss function with a KL divergence and a Gaussian distribution estimation-based approach. The method identifies distinguishable features and secures the inter-instance distance, thus fortifying the distance metrics between abnormal and normal instances approximated by distribution. The contribution of this research involves proposing a novel framework based on MIL for performing WSVAD and presenting an efficient integration strategy during the augmentation process. Extensive experiments were conducted on benchmark datasets XD-Violence and UCF-Crime to substantiate the effectiveness of the proposed model.

Low-Voltage-Driven SnO2-Based H2S Microsensor with Optimized Micro-Heater for Portable Gas Sensor Applications.

To realize portable gas sensor applications, it is necessary to develop hydrogen sulfide (H2S) microsensors capable of operating at lower voltages with high response, good selectivity and stability, and fast response and recovery times. A gas sensor with a high operating voltage (>5 V) is not suitable for portable applications because it demands additional circuitry, such as a charge pump circuit (supply voltage of common circuits is approximately 1.8−5 V). Among H2S microsensor components, that is, the substrate, sensing area, electrode, and micro-heater, the proper design of the micro-heater is particularly important, owing to the role of thermal energy in ensuring the efficient detection of H2S. This study proposes and develops tin (IV)-oxide (SnO2)-based H2S microsensors with different geometrically designed embedded micro-heaters. The proposed micro-heaters affect the operating temperature of the H2S sensors, and the micro-heater with a rectangular mesh pattern exhibits superior heating performance at a relatively low operating voltage (3−4 V) compared to those with line (5−7 V) and rectangular patterns (3−5 V). Moreover, utilizing a micro-heater with a rectangular mesh pattern, the fabricated SnO2-based H2S microsensor was driven at a low operating voltage and offered good detection capability at a low H2S concentration (0−10 ppm), with a quick response (<51 s) and recovery time (<101 s).