Anthropogenic fingerprints in daily precipitation revealed by deep learning.

According to twenty-first century climate-model projections, greenhouse warming will intensify rainfall variability and extremes across the globe1-4. However, verifying this prediction using observations has remained a substantial challenge owing to large natural rainfall fluctuations at regional scales3,4. Here we show that deep learning successfully detects the emerging climate-change signals in daily precipitation fields during the observed record. We trained a convolutional neural network (CNN)5 with daily precipitation fields and annual global mean surface air temperature data obtained from an ensemble of present-day and future climate-model simulations6. After applying the algorithm to the observational record, we found that the daily precipitation data represented an excellent predictor for the observed planetary warming, as they showed a clear deviation from natural variability since the mid-2010s. Furthermore, we analysed the deep-learning model with an explainable framework and observed that the precipitation variability of the weather timescale (period less than 10 days) over the tropical eastern Pacific and mid-latitude storm-track regions was most sensitive to anthropogenic warming. Our results highlight that, although the long-term shifts in annual mean precipitation remain indiscernible from the natural background variability, the impact of global warming on daily hydrological fluctuations has already emerged.

Analytical and Clinical Validation of Cell-Free Circulating Tumor DNA Assay for the Estimation of Tumor Mutational Burden.

BACKGROUND: Ultra-deep sequencing to detect low-frequency mutations in circulating tumor-derived DNA (ctDNA) increases the diagnostic value of liquid biopsy. The demand for large ctDNA panels for comprehensive genomic profiling and tumor mutational burden (TMB) estimation is increasing; however, few ctDNA panels for TMB have been validated. Here, we designed a ctDNA panel with 531 genes, named TMB500, along with a technical and clinical validation. METHODS: Synthetic reference cell-free DNA materials with predefined allele frequencies were sequenced in a total of 92 tests in 6 batches to evaluate the precision, linearity, and limit of detection of the assay. We used clinical samples from 50 patients with various cancers, 11 healthy individuals, and paired tissue samples. Molecular barcoding and data analysis were performed using customized pipelines. RESULTS: The assay showed high precision and linearity (coefficient of determination, r2 =0.87) for all single nucleotide variants, with a limit of detection of 0.24%. In clinical samples, the TMB500 ctDNA assay detected most variants present and absent in tissues, showing that ctDNA could assess tumor heterogeneity in different tissues and metastasis sites. The estimated TMBs correlated well between tissue and blood, except in 4 cases with extreme heterogeneity that showed very high blood TMBs compared to tissue TMBs. A pilot evaluation showed that the TMB500 assay could be used for disease monitoring. CONCLUSIONS: The TMB500 assay is an accurate and reliable ctDNA assay for many clinical purposes. It may be useful for guiding the treatment of cancers with diverse genomic profiles, estimating TMB in immune therapy, and disease monitoring.

Human contribution to more-intense precipitation extremes.

Extremes of weather and climate can have devastating effects on human society and the environment. Understanding past changes in the characteristics of such events, including recent increases in the intensity of heavy precipitation events over a large part of the Northern Hemisphere land area, is critical for reliable projections of future changes. Given that atmospheric water-holding capacity is expected to increase roughly exponentially with temperature--and that atmospheric water content is increasing in accord with this theoretical expectation--it has been suggested that human-influenced global warming may be partly responsible for increases in heavy precipitation. Because of the limited availability of daily observations, however, most previous studies have examined only the potential detectability of changes in extreme precipitation through model-model comparisons. Here we show that human-induced increases in greenhouse gases have contributed to the observed intensification of heavy precipitation events found over approximately two-thirds of data-covered parts of Northern Hemisphere land areas. These results are based on a comparison of observed and multi-model simulated changes in extreme precipitation over the latter half of the twentieth century analysed with an optimal fingerprinting technique. Changes in extreme precipitation projected by models, and thus the impacts of future changes in extreme precipitation, may be underestimated because models seem to underestimate the observed increase in heavy precipitation with warming.

Leveraging physics-based and explainable machine learning approaches to quantify the relative contributions of rain and air pollutants to wet deposition.

A quantitative understanding of the roles of rainfall and pollutant concentrations in wet deposition is important because they critically influence terrestrial and aquatic ecosystems. However, their relative contributions to wet deposition, which vary across regions, have not yet been identified. We propose two methods that quantitatively separate the contributions of rain and pollutant concentrations to wet deposition: one is based on simplified equations describing the wet scavenging of pollutants and the other is based on random forest models employing SHapley Additive exPlanations. Three-dimensional long-term air quality simulations from 2003 to 2019 are used as inputs for both the physics-based and machine learning models. Remarkably, the results drawn from the explainable machine learning model are consistent with those from the physics-based approach: overall, rain is a more important limiting factor than pollutant concentrations and the relative contribution of rain is larger than that of pollutants by up to a factor of 3-4 in polluted regions. In polluted regions, pollutant concentrations can remain relatively high even in the presence of precipitation owing to continuous and intense emissions; therefore, wet deposition is limited by rainfall. The contribution of rainfall is larger by 1.5-2.5 than that of pollutant concentrations in regions even with low emissions and this considerably large role of rain suggests that regional or transboundary pollutant transport plays a key role in modulating wet deposition. However, in very remote regions, once the rainfall amount exceeds a certain value, rainfall no longer contributes to increasing wet deposition because atmospheric pollutants are readily removed by rain. So, the contributions of the two factors are comparable in pristine regions. Our results can serve as a basis for explaining interannual variations in wet deposition and for future projections of wet deposition under emission control plans and climate change scenarios across regions.

Serial Circulating Tumor DNA Analysis with a Tumor-Naïve Next-Generation Sequencing Panel Detects Minimal Residual Disease and Predicts Outcome in Ovarian Cancer.

Circulating tumor DNA (ctDNA) may aid in personalizing ovarian cancer therapeutic options. Here, we aimed to assess the clinical utility of serial ctDNA testing using tumor-naïve, small-sized next-generation sequencing (NGS) panels. A total of 296 patients, including 201 with ovarian cancer and 95 with benign or borderline disease, were enrolled. Samples were collected at baseline (initial diagnosis or surgery) and every 3 months after that, resulting in a total of 811 blood samples. Patients received adjuvant therapy based on the current standard of care. Cell-free DNA was extracted and sequenced using an NGS panel of 9 genes: TP53, BRCA1, BRCA2, ARID1A, CCNE1, KRAS, MYC, PIK3CA, and PTEN. Pathogenic somatic mutations were identified in 69.2% (139/201) of patients with ovarian cancer at baseline but not in those with benign or borderline disease. Detection of ctDNA at baseline and/or at 6 months follow-up was predictive of progression-free survival (PFS). PFS was significantly poorer in patients with detectable pathogenic mutations at baseline that persisted at follow-up than in patients that converted from having detectable ctDNA at baseline to being undetectable at follow-up; survival did not differ between patients without pathogenic ctDNA mutations in baseline or follow-up samples and those that converted from ctDNA positive to negative. Disease recurrence was also detected earlier with ctDNA than with conventional radiologic assessment or CA125 monitoring. These findings demonstrate that serial ctDNA testing could effectively monitor patients and detect minimal residual disease, facilitating early detection of disease progression and tailoring of adjuvant therapies for ovarian cancer treatment. SIGNIFICANCE: In ovarian cancer, serial circulating tumor DNA testing is a highly predictive marker of patient survival, with a significantly improved recurrence detection lead time compared with conventional monitoring tools.

Synthesized Pheophorbide a-mediated photodynamic therapy induced apoptosis and autophagy in human oral squamous carcinoma cells.

BACKGROUND: Pheophorbide a (Pa) is a chlorine-based photosensitizer derived from an ethnopharmacological herb, and our group recently synthesized Pa by the removal of a magnesium ion and a phytyl group from chlorophyll-a. In this study, the effect of photodynamic therapy (PDT) with synthesized Pa was examined in a human oral squamous cell carcinoma (OSCC) cells. METHODS: Cells were treated with PDT with Pa, and reactive oxygen species (ROS) and mitochondrial membrane potential [ΔΨ (m)] were examined. Apoptosis was measured using annexin V staining and immunoblot. Autophagy was characterized by the increase in LC3B-II and the formation of autophagosome and acidic vesicular organelles (AVOs). RESULTS: Pa-PDT inhibited the proliferation of OSCC cells in a dose-dependent manner. Pa-PDT increased the number of apoptotic cells by inactivating ERK pathway. Pa-PDT also induced autophagy in OSCC cells evidenced by the increased levels of LC3 type II expression and the accumulation of AVOs. The inhibition of autophagy enhanced Pa-PDT-mediated cytotoxicity through an increase in necrosis. CONCLUSIONS: These results suggest that synthesized Pa-PDT exerts anti-tumor effects by inducing apoptosis and autophagy and provide novel evidence that Pa-PDT induces autophagy, and autophagy inhibition enhances Pa-PDT-mediated necrosis in OSCC cells.

Observationally-constrained projections of an ice-free Arctic even under a low emission scenario.

The sixth assessment report of the IPCC assessed that the Arctic is projected to be on average practically ice-free in September near mid-century under intermediate and high greenhouse gas emissions scenarios, though not under low emissions scenarios, based on simulations from the latest generation Coupled Model Intercomparison Project Phase 6 (CMIP6) models. Here we show, using an attribution analysis approach, that a dominant influence of greenhouse gas increases on Arctic sea ice area is detectable in three observational datasets in all months of the year, but is on average underestimated by CMIP6 models. By scaling models' sea ice response to greenhouse gases to best match the observed trend in an approach validated in an imperfect model test, we project an ice-free Arctic in September under all scenarios considered. These results emphasize the profound impacts of greenhouse gas emissions on the Arctic, and demonstrate the importance of planning for and adapting to a seasonally ice-free Arctic in the near future.

Exploring the Characteristics of Circulating Tumor DNA in Pt1a Clear Cell Renal Cell Carcinoma: A Pilot Study.

Circulating tumor DNA (ctDNA) is a promising biomarker for clear cell renal cell carcinoma (ccRCC); however, its characteristics in small renal masses of ccRCC remain unclear. In this pilot study, we explored the characteristics of ctDNA in pT1a ccRCC. Plasma samples were collected preoperatively from 53 patients with pT1a ccRCC. The ctDNA of pT1a ccRCC was profiled using next-generation sequencing and compared with that of higher-stage ccRCC. The association of ctDNA in pT1a ccRCC with clinicopathological features was investigated. The positive relationship of mutations between ctDNA and matched tissues was evaluated. In pT1a ccRCC, the ctDNA detection rate, cell-free DNA concentration, and median variant allele frequency were 20.8%, 5.8 ng/mL, and 0.38%, respectively, which were significantly lower than those in metastatic ccRCC. The ctDNA gene proportions in pT1a samples differed from those in metastatic ccRCC samples. The relationships between ctDNA and tumor size, tumor grade, and patient age were not elucidated. The positive concordance between ctDNA and matched tissues was poor for pT1a ccRCC. Strategies are needed to increase sensitivity while eliminating noise caused by clonal hematopoiesis to increase the clinical utility of ctDNA analysis in small renal masses of ccRCC.

Increase in convective extreme El Niño events in a CO2 removal scenario.

Convective extreme El Niño (CEE) events, characterized by strong convective events in the eastern Pacific, are known to have a direct link to anomalous climate conditions worldwide, and it has been reported that CEE will occur more frequently under greenhouse warming. Here, using a set of CO2 ramp-up and ramp-down ensemble experiments, we show that frequency and maximum intensity of CEE events increase further in the ramp-down period from the ramp-up period. These changes in CEE are associated with the southward shift of the intertropical convergence zone and intensified nonlinear rainfall response to sea surface temperature change in the ramp-down period. The increasing frequency of CEE has substantial impacts on regional abnormal events and contributed considerably to regional mean climate changes to the CO2 forcings.

Hemispherically asymmetric Hadley cell response to CO2 removal.

A poleward shift of the Hadley cell (HC) edge in a warming climate, which contributes to the expansion of drought-prone subtropical regions, has been widely documented. The question addressed here is whether this shift is reversible with CO2 removal. By conducting large-ensemble experiments where CO2 concentrations are systematically increased and then decreased to the present-day level, we show that the poleward-shifted HC edge in a warming climate does not return to its present-day state when CO2 concentrations are reduced. While the Southern Hemisphere HC edge remains poleward of its present-day state, the Northern Hemisphere HC edge ends up farther equatorward of its present-day state. Such hemispherically asymmetric HC edge changes are closely associated with the changes in vertical wind shear in the subtropical atmosphere, which result from the long adjustment time of the ocean response to CO2 removal. Our findings suggest that CO2 removal may not guarantee the recovery of the subtropical dryness associated with the HC changes.

Toll-like receptor 7 agonist, imiquimod, inhibits oral squamous carcinoma cells through apoptosis and necrosis.

BACKGROUND: Toll-like receptor (TLR) agonists have anticancer effect by inducing apoptosis or activating immune cells. In this study, we investigated whether imiquimod, TLR7 agonist, inhibits the proliferation of oral cancer cells. METHODS: Toll-like receptor 7 expression and IL-6/8 production by imiquimod were examined using RT-PCR and Enzyme-linked immunosorbent assay, respectively. Cell viability was examined by MTT assay. To examine apoptotic cell death, Annexin V/PI staining for flow cytometry and Western blot analysis were performed. Necrotic cell death was determined by leakage of lactate dehydrogenase (LDH), HMGB1, and PI staining in imiquimod-treated oral squamous cell carcinoma (OSCC) cells. RESULTS: Toll-like receptor 7 mRNA was expressed in OSCC cells. Imiquimod induced IL-6 and IL-8 production in OSCC cells, suggesting the functional expression of TLR7. Imiquimod inhibited cells proliferation in a dose-dependent manner. The ratio of annexin V-positive cells and cleaved caspase-3/7 was increased by imiquimod treatment in OSCC cells, suggesting that imiquimod-induced cell death in OSCC cells may be owing to apoptosis. In addition, LDH secretion and PI staining were detected in OSCC cells treated with imiquimod, showing that imiquimod also induced necrotic cell death in the OSCC cells. CONCLUSIONS: Imiquimod inhibited effectively the growth of OSCC cells by inducing apoptosis and necrosis.

Synchronous central giant cell granuloma and ossifying fibroma of the mandible.

Central giant cell granuloma (CGCG) is a benign lesion of the jaws. In most cases, the lesion presents as a painless, slow-growing swelling of the jaws. Ossifying fibroma (OF) of the jaw is a benign neoplasm that consists of variable amounts of mineralized material embedded in a fibrous stroma. The simultaneous occurrence of CGCG with odontogenic fibroma or OF has been described as combined lesions. However, synchronous presentation of CGCG and OF in the mandible is a rare occurrence. This report describes a case of 2 completely independent CGCG and OF located on both posterior regions of the mandible.

Evaluation of early bone response to fluoride-modified and anodically oxidized titanium implants through continuous removal torque analysis.

PURPOSE: To compare between a bioactive and a bioinert implant with different geometries by continuous measurement of the removal torque and calculation of the angular momentum of each surfaced implant. MATERIALS AND METHODS: Six New Zealand white rabbits were used in the study. Each rabbit received 2 implants. A bioactive fluoride-modified implant with a conical connection and microthread design was inserted into one tibia, and a bioinert anodically oxidized implant with an external connection design was inserted into the other. After 2 weeks of implant insertion, the removal torque values were continuously measured according to time. Using the time-torque curve resulting from the measurements, the maximum values were determined, and the angular momenta were calculated. RESULTS: The anodically oxidized implant had significantly higher peak removal torque and angular momentum values than the fluoride-modified implant (P < 0.05). CONCLUSIONS: The impact of the fluoride-modified bioactive implant on early bone response remains unclear. Considering the angular momentum of dental implants may assist in the elucidation of the effect of implant geometry on bone response.

Greenhouse warming and anthropogenic aerosols synergistically reduce springtime rainfall in low-latitude East Asia.

Low-latitude East Asia, particularly southern China, has experienced a markedly decreasing springtime rainfall in recent years whereas rainfall trends are weak in mid-latitude East Asia. Details of human influences on this contrasting feature remain uncertain. This study provides a quantification of the relative roles of greenhouse warming and aerosols in the observed spring rainfall trends over East Asia using a state-of-the-art numerical model. Greenhouse warming drives more rapid temperature increases over high-latitude East Asia potentially associated with reduced spring snow than the western North Pacific, which induces an anomalous anticyclone over the East China Sea. This circulation change results in a northwestward extension of the western North Pacific subtropical high, reducing rainfall at low latitudes while moderately increasing rainfall at mid-latitudes. In contrast, anthropogenic aerosols reduce rainfall in both low- and mid-latitude East Asia. Hence, the two anthropogenic factors synergistically reduce rainfall at low latitudes, with a stronger contribution of greenhouse warming (~34%) than aerosols (~17%). In mid-latitude East Asia, their contributions are offset, resulting in weak rainfall trends. Further, the anthropogenic influences are found to be relatively larger under drier conditions, suggesting that a more severe drought can occur in low-latitude East Asia under future drought-conducive conditions.

Asymmetrical response of summer rainfall in East Asia to CO2 forcing.

Understanding the regional hydrological response to varying CO2 concentration is critical for cost-benefit analysis of mitigation and adaptation polices in the near future. To characterize summer monsoon rainfall change in East Asia in a changing CO2 pathway, we used the Community Earth System Model (CESM) with 28 ensemble members in which the CO2 concentration increases at a rate of 1% per year until its quadrupling peak, i.e., 1468 ppm (ramp-up period), followed by a decrease of 1% per year until the present-day climate conditions, i.e., 367 ppm (ramp-down period). Although the CO2 concentration change is symmetric in time, the amount of summer rainfall anomaly in East Asia is increased 42% during a ramp-down period than that during a ramp-up period when the two periods of the same CO2 concentration are compared. This asymmetrical rainfall response is mainly due to an enhanced El Niño-like warming pattern as well as its associated increase in the sea surface temperature in the western North Pacific during a ramp-down period. These sea surface temperature patterns enhance the atmospheric teleconnections and the local meridional circulations around East Asia, resulting in more rainfall over East Asia during a ramp-down period. This result implies that the removal of CO2 does not guarantee the return of regional rainfall to the previous climate state with the same CO2 concentration.

Volcanic-induced global monsoon drying modulated by diverse El Niño responses.

There remains large intersimulation spread in the hydrologic responses to tropical volcanic eruptions, and identifying the sources of diverse responses has important implications for assessing the side effects of solar geoengineering and improving decadal predictions. Here, we show that the intersimulation spread in the global monsoon drying response strongly relates to diverse El Niño responses to tropical eruptions. Most of the coupled climate models simulate El Niño-like equatorial eastern Pacific warming after volcanic eruptions but with different amplitudes, which drive a large spread of summer monsoon weakening and corresponding precipitation reduction. Two factors are further identified for the diverse El Niño responses. Different volcanic forcings induce systematic differences in the Maritime Continent drying and subsequent westerly winds over equatorial western Pacific, varying El Niño intensity. The internally generated warm water volume over the equatorial western Pacific in the pre-eruption month also contributes to the diverse El Niño development.

Second primary cancers in patients with oral cavity cancer included in the Korea Central Cancer Registry.

OBJECTIVES: The improved survival of patients with oral cavity cancer (OCC) has generated interest in factors affecting survivorship, particularly among second primary cancer (SPC) patients. This study aimed to assess the incidence, patterns, and risk factors for SPC after OCC treatment in the Korean population. MATERIALS AND METHODS: Data from 15,261 patients with OCC (ICD-O: C01-C06) identified between 1993 and 2014 were extracted from the Korean Central Cancer Registry. The standardized incidence ratio (SIR) for SPC after index OCC was calculated, and Poisson regression analysis was performed to evaluate the risk factors for SPC among survivors. RESULTS: The overall SIR for SPC among OCC survivors was 1.47 (95% confidence interval [CI] 1.39-1.56). SIR differed by sex (male: 1.51 vs. female: 1.37), age at diagnosis (<45 years: 2.47 vs. 45-64 years: 1.68 vs. ≥ 65 years: 1.10), index OCC subsite (floor of mouth: 1.95 vs. gum: 1.30), follow-up duration (6-23 months: 1.64 vs. 24-59 months: 1.51 vs. 60-119 months: 1.48 vs. ≥ 120 months: 1.24), histological OCC type (salivary gland malignancy: 1.77 vs. squamous cell carcinoma: 1.44 vs. others: 1.47), and radiation history (any: 1.94 vs. no radiation: 1.37). The risk factors for SPC development among OCC survivors included younger age at diagnosis and history of radiation therapy. CONCLUSION: OCC survivors have significantly increased risks of SPCs, exhibiting distinctive site distributions and chronological patterns. These patients would benefit from an SPC surveillance protocol.

Endoplasmic reticulum stress is involved in hydrogen peroxide induced apoptosis in immortalized and malignant human oral keratinocytes.

BACKGROUND: Although hydrogen peroxide may play an important role in the development of cancer, it can be an efficient inducer of apoptosis in cancer cells; the exact mechanism by which this action occurs is not completely understood in oral cancer cells. METHOD: In this study, the mechanisms by which H(2)O(2) inhibited growth and induced apoptosis were differentially investigated using HPV-immortalized human oral keratinocytes (IHOK) and oral cancer cells (HN4). RESULTS: H(2)O(2) treatment sensitively and dose-dependently induced growth inhibition and typical apoptosis in IHOK and HN4 cells, as demonstrated by a decreased level of cell viability, an increased population of cells in the sub-G(0)/G(1) phase, ladder formation of the genomic DNA, chromatin condensation and accumulation of Annexin V(+)/PI(+) cells. Furthermore, the expression of Bax, p53 and p21(WAF1/CIP1) increased, whereas the expression of Bcl-2 decreased in immortalized and malignant keratinocytes that were treated with H(2)O(2). In addition, cytochrome-c from the mitochondria was observed in H(2)O(2)-treated IHOK and oral cancer cells, and this was accompanied by the activation of caspase-3 and -9. Additionally, H(2)O(2) treatment induced upregulation of CHOP, GRP78 and several representative endoplasmic reticulum (ER) stress-responsive proteins, including heme oxygenase-1. CONCLUSION: Overall, these results suggest that H(2)O(2) triggers apoptosis via the mitochondrial and ER stress pathway in IHOK and HN4 cells, and that increasing the cellular levels of H(2)O(2) sufficiently may lead to selective killing of oral cancer cells and therefore be therapeutically useful.

Differential induction of heme oxygenase-1 against nicotine-induced cytotoxicity via the PI3K, MAPK, and NF-kappa B pathways in immortalized and malignant human oral keratinocytes.

BACKGROUND: Heme oxygenase-1 (HO-1) exhibits cytoprotective effects in many different cell types and is induced by nicotine exposure in human gingival fibroblasts. However, the role of HO-1 in cancer cells exposed to nicotine has not previously been described. METHODS: We investigated the effects of nicotine on HO-1 protein expression and cell viability in immortalized (IHOK) and malignant (HN12) human oral keratinocyte cells using the 3,4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide assay and Western blotting. We also examined the involvement of the phosphoinositide-3-kinase (PI3K), mitogen-activated protein kinase (MAPK), and nuclear factor-kappaB (NF-kappaB) signaling pathways in nicotine-induced cytotoxicity and HO-1 levels in IHOK and HN12 cells. RESULTS: Nicotine-induced HO-1 production and had cytotoxic effects on cells in both a concentration- and time-dependent manner. Nicotine-induced cytotoxicity and accumulation of HO-1 were greater in IHOK cells than in HN12 cells. Molecular inhibitors of the ERK, p38 MAP kinase, PI3 K, and NF-kappaB signaling pathways blocked the cytotoxic effects and induction of HO-1 expression by nicotine. Treatment with antioxidants (bilirubin, N-acetylcysteine) protected cells against nicotine-induced cytotoxicity and blocked the upregulation of HO-1, the effects of which were more pronounced in IHOK cells than in HN12 cells. CONCLUSIONS: Collectively, these results suggest that HO-1 plays a principal role in the protective response to nicotine in oral cancer and immortalized keratinocytes. Moreover, the addition of exogenous antioxidants may help to protect oral epithelial cells as chemopreventive agents against nicotine-induced oxidative stress.

Electrostatic force microscopy measurements of charge trapping behavior of Au nanoparticles embedded in metal-insulator-semiconductor structure.

Charge trapping properties of electrons and holes in Au nanoparticles embedded in metal-insulator-semiconductor (MIS) on p-type Si (100) substrates were investigated by electrostatic force microscopy (EFM). The Au nanoparticles were prepared with a unique laser irradiation method and charged by applying a bias voltage between EFM tip and sample. The EFM system was used to image charged areas and to determine quantitatively the amount of stored charge in the Au nanoparticle-inserted MIS structure. In addition, charge trapping characteristics of the samples were carried out with electrical measurements, such as capacitance-voltage and current-voltage measurement for memory characteristics. Finally, the comparison of EFM results with the electrically measured data was done to determine the amount of stored charge in the Au nanoparticle-inserted MIS structure, confirming the usefulness of EFM system for the characterization of nanoparticle-based non-volatile devices.