Cryptocyanine-based probes exhibit highly efficient photothermal conversion and represent a new class of photothermal agents for use in photothermal therapy (PTT). With the thermal susceptibility of ...mitochondria in mind, we have prepared a mitochondria-targeted, NIR-absorbing cryptocyanine probe (Mito-CCy) and evaluated its photophysical properties, photothermal conversion efficiency, biological compatibility, cytotoxicity, and mitochondrial localization in HeLa cells. Upon subjecting 0.5 mL of a PBS buffer solution (10 mM, pH 7.4, containing 50% DMSO) of Mito-CCy (0.5 mM) to 730 nm laser irradiation at 2.3 W/cm2, the temperature of the solution increased by 13.5 °C within 5 min. In contrast, the corresponding cryptocyanine (CCy) lacking the triarylphosphonium group gave rise to only an ∼3.4 °C increase in solution temperature under otherwise identical conditions. Mito-CCy also exhibited high cytotoxicity in HeLa cells when subject to photoirradiation. This light-induced cytotoxicity is attributed to the endogenous production of reactive oxygen species (ROS) induced under conditions of local heating. ROS are known to interfere with the mitochondrial defense system and to trigger apoptosis. By targeting the mitochondria, the present sensitizer-based photothermogenic approach is rendered more effective. As such, the system reported here represents the vanguard of what might be a new generation of organelle-targeted photothermal therapeutics.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
Brain-derived exosomes released into the blood are considered a liquid biopsy to investigate the pathophysiological state, reflecting the aberrant heterogeneous pathways of pathological progression ...of the brain in neurological diseases. Brain-derived blood exosomes provide promising prospects for the diagnosis of neurological diseases, with exciting possibilities for the early and sensitive diagnosis of such diseases. However, the capability of traditional exosome isolation assays to specifically isolate blood exosomes and to characterize the brain-derived blood exosomal proteins by high-throughput proteomics for clinical specimens from patients with neurological diseases cannot be assured. We report a magnetic transferrin nanoparticles (MTNs) assay, which combined transferrin and magnetic nanoparticles to isolate brain-derived blood exosomes from clinical samples.
The principle of the MTNs assay is a ligand-receptor interaction through transferrin on MTNs and transferrin receptor on exosomes, and electrostatic interaction via positively charged MTNs and negatively charged exosomes to isolate brain-derived blood exosomes. In addition, the MTNs assay is simple and rapid (< 35 min) and does not require any large instrument. We confirmed that the MTNs assay accurately and efficiently isolated exosomes from serum samples of humans with neurodegenerative diseases, such as dementia, Parkinson's disease (PD), and multiple sclerosis (MS). Moreover, we isolated exosomes from serum samples of 30 patients with three distinct neurodegenerative diseases and performed unbiased proteomic analysis to explore the pilot value of brain-derived blood protein profiles as biomarkers.
Using comparative statistical analysis, we found 21 candidate protein biomarkers that were significantly different among three groups of neurodegenerative diseases.
The MTNs assay is a convenient approach for the specific and affordable isolation of extracellular vesicles from body fluids for minimally-invasive diagnosis of neurological diseases.
Multiple valve unit (MVU), which converts AC to DC and DC to AC, is one of the key elements of high voltage DC (HVDC) transmission. Therefore, the insulation design of MVU against overvoltage should ...be considered for the stable and reliable operation of HVDC transmission system. Especially, the air clearance of MVU should be calculated based the switching impulse, since it is fatal to MVU in terms of electrical insulation. However, the previous studies were limited to wave front, and the air clearance of the switching impulse is specified only for an ultra-high voltage (UHV) above 750 kV. As a result, it is difficult to calculate the air clearance of MVU which must endure for a switching impulse under 750 kV. In addition, when the switching impulse introduced while the MVU is in normal operation, it is superimposed to DC and creates the most severe situation, but the studies on such subjects are also insufficient. Therefore, as a fundamental step to calculate the air clearance of MVU, the dielectric characteristics of switching impulse and DC superimposed switching impulse in air have been investigated. The experiments on switching impulse showed that the critical flashover voltage was varied according to the curvature of electrode in the gap distance, up to eight times of the electrode radius. However, beyond that gap distance, the critical flashover voltage became similar, regardless of the radius of electrodes. In case of the superimposed experiment, it was performed according to DC pre-stress level and the polarities of switching impulse. The results were most severe when the positive switching impulse was superimposed on the positive DC, and the peak voltage at which flashover occurs was independent of DC pre-stress.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This paper introduces the smallest dynamic random access memory (DRAM) cell, which was implemented using a new transistor structure, the dual work function - buried channel array transistor ...(DWF-BCAT). For the first time, a feature size of approximately 17 nm was achieved for a DRAM cell. In this study, a novel cell gate oxide process that mitigates traps in the gate oxide and gate interface, whose dimensions scale concurrently, was developed to fabricate the DWF-BCAT. By utilizing a three-step process involving in-situ steam generation (ISSG) followed by atomic layer deposition (ALD) then another cycle of ISSG (IAI) to create the dual work function gate, a significant improvement in DRAM data retention characteristics is achieved. A new barrier fabrication process called plasma nitridation treatment of oxide film (PNOF) was also developed. Oxide film barriers for two gate materials, namely tungsten and polycrystalline Si, were deposited using PNOF. Device characterization results reveal that PNOF is highly effective in reducing interfacial resistance by suppressing the inter-diffusion of gate materials, leading to improved DRAM write time characteristics. Additionally, gate oxide defects can be repaired and surface contamination can be removed by applying an HF wet strip (HFWS) process. The BCAT design and fabrication strategies applied in this study can accelerate the miniaturization of DRAMs toward the theoretical scaling limit.
Two novel synthetic approaches for synthesizing (E)-3-(1,3-diarylallylidene)oxindoles from oxindole were developed. All previously reported methods for synthesizing 3-(1,3-diarylallylidene)oxindoles ...utilized palladium-catalyzed reactions as a key step to form this unique skeleton. Despite high efficiency, palladium-catalyzed reactions have limitations in terms of substrate scope. Especially, an iodoaryl moiety cannot be introduced by the previous methods due to its high reactivity toward the palladium catalyst. Our Knoevenagel/allylic oxidation/Wittig and Knoevenagel/aldol/dehydration strategies complement each other and show broad substrate scope, including substrates with iodoaryl groups. The current methods utilized acetophenones, benzylidene phosphonium ylides, and benzaldehydes that are commercially available or easily accessible. Thus, the current synthetic approaches to (E)-3-(1,3-diarylallyldiene)oxindoles are readily amendable for variety of oxindole derivatives.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
No studies of the current status of treatment options are available for ankylosing spondylitis (AS) patients in South Korea. This study assesses the current status of AS treatment trends using a ...nationwide database. This study was conducted using a Korean National Health Insurance System (KNHIS) dataset from 2006 to 2016. We randomly extracted 50% of the total number of patients registered as As patients in the KNHIS. The distribution of the number of patients according to age and gender was analyzed each year. The types and combination methods of drugs used during the study period were estimated yearly. Between 2006 and 2016, the number of AS patients increased linearly by an average of 9% annually, 6372 in 2006 to 15188 in 2016. The study found that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) was the most commonly prescribed pharmacological treatment option, followed by disease-modifying anti-rheumatic drugs (DMARDs) and then biologics. Biologics such as tumor necrosis factor alpha (TNF-α) inhibitors increased from 10% to 35% consistently for 10 years. In terms of combination therapy, DMARDs + NSAIDs accounted for almost 90% of treatments in 2006, but decreased by 65% in 2016. The use of biologics and NSAIDs increased from 3% to 28%. Prescriptions for dual therapies and mono therapies largely dominated prescription habits, accounted for up to approximately 80% of treatments. Among 10- to 14-year-old patients, there was no triple therapy, dual and triple therapies decreased gradually for those 60 and older, and the ratio of conservative treatments has increased. This study shows how South Korea reflects changes in AS treatment trends, along with the emergence of TNF-α inhibitors that are effective in treating AS. Research on clinical outcomes for AS treatments will be needed on following these drug changes.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Herein, we report the use of two-photon fluorogenic probes using tetrazine-based bioorthogonal reactions with multicolor emissions that cover nearly all of the visible region. New fluorogenic probes ...were designed based on donor–acceptor-type naphthalene structures conjugated with a fluorescence-quenching tetrazine moiety for turn-on properties in one- and two-photon fluorescence. Our fluorescent probes showed a moderate to good turn-on ratio after bioorthogonal inverse electron demand Diels–Alder cycloaddition with trans-cyclooctenol in one- and two-photon fluorescence. We successfully applied our probes to mitochondria- and lysosome-selective bioorthogonal imaging in live cells with one-/two-photon and one-photon microscopy, respectively.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
A converter valve unit, which converts Alternating Current (AC) to Directing Current (DC) and DC to AC, is one of the key elements of high voltage direct current (HVDC) transmission. The insulation ...design of a converter valve unit should be considered for air clearance according to the DC superimposed overvoltage and the insulator that maintains the insulation performance and the corona shield to suppress DC corona discharge. There is no prescribed standard for the insulation design of a converter valve unit. Moreover, insulation performance under an applied DC voltage has not yet been thoroughly investigated. Therefore, it is necessary to study the insulation design method of the converter valve unit. In this paper, consideration of the insulation design method on a ±200 kV converter valve unit in an HVDC converter hall is performed. The finite element method (FEM) is used to simulate the 3D model. Additionally, the safety factor (SF) is applied in accordance with the dielectric test in IEC 62271-1. As a result, an insulation design process on the converter valve unit is proposed and the insulation design is carried through the design factors. It is confirmed that design factors on the air clearance, insulator and corona shield have a significant effect on a highly reliable insulation design.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Physical activity (PA) is one of the most important modifiable factors associated with fracture risk. However, the association between interval changes in PA and the risk of fracture remains unknown. ...We investigated the risk of fracture development according to interval changes in PA in middle aged and older individuals. In this nationwide cohort study of adults aged ≥ 40 years, more than 4.9 million individuals without fractures within the last year who underwent two consecutive national health screenings in Korea from 2009 to 2012 were identified. The risk of fracture between 2013 and 2016 according to interval changes in regular PA was prospectively analyzed. Compared to individuals with a continuous lack of PA, those with a decrease in PA (0.41/1000 person-years (PY) decrease in incidence rate (IR); adjusted hazard ratio (aHR) 0.975; 95% confidence interval (CI) 0.964-0.987), increase in PA (1.8/1000 PY decrease in IR; aHR 0.948; 95% CI 0.937-0.959), and continuous PA (3.58/1000 PY decrease in IR; aHR 0.888; 95% CI 0.875-0.901) had a significantly reduced risk of fracture. Interval changes in regular PA were associated with risk of fracture. Individuals who engaged in continuous regular PA exhibited the maximum protective benefit against fracture.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
As polypropylene laminated paper (PPLP) is usually wound around the high-voltage conductor of a dc high-temperature superconducting power cable several times, it is needed to determine whether ...electrical conductivity of PPLP could be increased according to the number of layers. In thin films without layers, electrical conductivity increases according to the thickness of materials. For this reason, the effect of the number of PPLP layers on electrical conductivity needs to be verified because the dc electric field distribution is highly influenced by electrical conductivity. In this paper, to determine the effect of PPLP layers on electrical conductivity, we measured the conductivity of specimens with single, double, and quadruple layers of PPLP in liquid nitrogen (LN 2 ), and compared the results according to layer number. In addition, we measured the electrical conductivity of specimens with single, double, and quadruple layers of Kraft to verify if there was a layer effect or not. The electrical conductivity of the PPLP and Kraft specimens did not change with an increase in the number of layers. Therefore, we concluded that the electrical conductivity of single-layered PPLP and Kraft specimens can be used in dc electric field simulations.