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Influenza A virus causes numerous deaths and infections worldwide annually. Therefore, we have considered nanobodies as a potential treatment for patients with severe cases of influenza. We developed a nanobody that was expected to have protective efficacy against the A/California/04/2009 (CA/04; pandemic 2009 flu strain) and evaluated its therapeutic efficacy against CA/04 in mice experiments. This nanobody was derived from the immunization of the alpaca, and the inactivated CA/04 virus was used as an immunogen. We successfully generated a nanobody library through bio-panning, phage ELISA, and Bio-layer interferometry. Moreover, we confirmed that administering nanobodies after lethal doses of CA/04 reduced viral replication in the lungs and influenza-induced clinical signs in mice. These research findings will help to develop nanobodies as viral therapeutics for CA/04 and other infectious viruses.

Abstract Sepsis is a dysregulated immune response to infection that leads to organ dysfunction and is associated with a high incidence and mortality rate. The lack of reliable biomarkers for diagnosing and prognosis of sepsis is a major challenge in its management. We aimed to investigate the potential of three-dimensional label-free CD8 + T cell morphology as a biomarker for sepsis. This study included three-time points in the sepsis recovery cohort (N = 8) and healthy controls (N = 20). Morphological features and spatial distribution within cells were compared among the patients’ statuses. We developed a deep learning model to predict the diagnosis and prognosis of sepsis using the internal cell morphology. Correlation between the morphological features and clinical indices were analysed. Cell morphological features and spatial distribution differed significantly between patients with sepsis and healthy controls and between the survival and non-survival groups. The model for predicting the diagnosis and prognosis of sepsis showed an area under the receiver operating characteristic curve of nearly 100% with only a few cells, and a strong correlation between the morphological features and clinical indices was observed. Our study highlights the potential of three-dimensional label-free CD8 + T cell morphology as a promising biomarker for sepsis. This approach is rapid, requires a minimum amount of blood samples, and has the potential to provide valuable information for the early diagnosis and prognosis of sepsis.

Magnetic soft composites have emerged as a promising soft actuator with a high degree of precision in the magnetic field stimuli system. But, their mass manufacturing strategies have yet to be developed, and most studies focus on small-scale near-net shaping production. Here, we first apply injection molding (which only takes a few seconds to shape) to fabricate the stimuli-responsive flexible micropillar composites with magnetic particle alignment design using an external magnetic field. The arrays exhibit magnetically anisotropic particle alignment up to 82.57 % along the longitudinal direction, showing a magnetic bending actuation response. We achieve a structural novelty of the magnetic micropillar with a high aspect ratio of up to 10 and pattern sizes of 50 μm via sacrificial LIGA insert mold and magneto-induced injection molding. For advanced mass production, the permanent metal mold is also applied to develop the micropillar composites based on the mechanical demolding approach; successful manufacturing is achieved by fabricating defect-free micropillar with 200 μm cylindrical pattern size and aspect ratio of 6. Further, the effect of powder volume fraction on the magneto-rheological behavior and corresponding magnetic performance is characterized in the injection molding process. The magnetic particle alignment trend is confirmed by the torque balance and the criteria of critical solids loading. Finally, we establish an injection molding process for magnetic soft composites, and verify the optimal powder fraction for the particle alignment.

Triple-negative breast cancer (TNBC) is associated with metabolic heterogeneity and poor prognosis with limited treatment options. New treatment paradigms for TNBC remains an unmet need. Thus, therapeutics that target metabolism are particularly attractive approaches. We previously designed organometallic Au(III) compounds capable of modulating mitochondrial respiration by ligand tuning with high anticancer potency in vitro and in vivo. Here, we show that an efficacious Au(III) dithiocarbamate (AuDTC) compound induce mitochondrial dysfunction and oxidative damage in cancer cells. Efficacy of AuDTC in TNBC mouse models harboring mitochondrial oxidative phosphorylation (OXPHOS) dependence and metabolic heterogeneity establishes its therapeutic potential following systemic delivery. This provides evidence that AuDTC is an effective modulator of mitochondrial respiration worthy of clinical development in the context of TNBC. One sentence summary: Metabolic-targeting of triple-negative breast cancer by gold anticancer agent may provide efficacious therapy.

Abstract Our previous work showed that KRAS activation in gastric cancer cells leads to activation of an epithelial-to-mesenchymal transition (EMT) program and generation of cancer stem-like cells (CSCs). Here we analyze how this KRAS activation in gastric CSCs promotes tumor angiogenesis and metastasis. Gastric cancer CSCs were found to secrete pro-angiogenic factors such as vascular endothelial growth factor A (VEGF-A), and inhibition of KRAS markedly reduced secretion of these factors. In a genetically engineered mouse model, gastric tumorigenesis was markedly attenuated when both KRAS and VEGF-A signaling were blocked. In orthotropic implant and experimental metastasis models, silencing of KRAS and VEGF-A using shRNA in gastric CSCs abrogated primary tumor formation, lymph node metastasis, and lung metastasis far greater than individual silencing of KRAS or VEGF-A. Analysis of gastric cancer patient samples using RNA sequencing revealed a clear association between high expression of the gastric CSC marker CD44 and expression of both KRAS and VEGF-A, and high CD44 and VEGF-A expression predicted worse overall survival. In conclusion, KRAS activation in gastric CSCs enhances secretion of pro-angiogenic factors and promotes tumor progression and metastasis.

Abstract The efficacy of decompressive craniectomy (DC) for traumatic brain injury (TBI) have been investigated in two recent randomized clinical trials (RCTs) and DC is recommended as an optional treatment for improving overall survival compared to medical treatment. However, the two RCTs enrolled extremely young adults, and the efficacy of DC in older adults remains questionable. Therefore, to identify the efficacy of DC in older adults, we compared patients who received medical care with those who underwent DC after propensity score matching (PSM). From the Korea Multi-center Traumatic Brain Injury Database, 443 patients identified as having intracranial hypertension and a necessity of DC were retrospectively enrolled. The patients were classified into the DC (n = 375) and non-DC (n = 68) groups according to operation records. The PSM was conducted to match the patients in the DC group with those receiving medical care (non-DC). After PSM, the newly matched group (DC, n = 126) was compared with patients without DC (non-DC, n = 63). The mean difference in the logit of the propensity scores (LPS) was 0.00391 and the mean age of enrolled patients were 65 years. The results of the comparative analyses after PSM showed that the 6-month mortality rate of the non-DC group was higher than that of the DC group (61.9% vs. 51.6%, p = 0.179). In terms of favorable outcomes (modified Rankin Scale [mRS] score

Atopic dermatitis (AD) is a common inflammatory skin disease caused by an immune disorder. Mast cells are known to be activated and granulated to maintain an allergic reaction, including rhinitis, asthma, and AD. Although hypoxia-inducible factor-1 alpha (HIF-1α) and signal transducer and activator of transcription 5 (STAT5) play crucial roles in mast cell survival and granulation, their effects need to be clarified in allergic disorders. Thus, we designed decoy oligodeoxynucleotide (ODN) synthetic DNA, without open ends, containing complementary sequences for HIF-1α and STAT5 to suppress the transcriptional activities of HIF-1α and STAT5. In this study, we demonstrated the effects of HIF-1α/STAT5 ODN using AD-like in vivo and in vitro models. The HIF-1α/STAT5 decoy ODN significantly alleviated cutaneous symptoms similar to AD, including morphology changes, immune cell infiltration, skin barrier dysfunction, and inflammatory response. In the AD model, it also inhibited mast cell infiltration and degranulation in skin tissue. These results suggest that the HIF-1α/STAT5 decoy ODN ameliorates the AD-like disorder and immunoglobulin E (IgE)-induced mast cell activation by disrupting HIF-1α/STAT5 signaling pathways. Taken together, these findings suggest the possibility of HIF-1α/STAT5 as therapeutic targets and their decoy ODN as a potential therapeutic tool for AD.

Abstract Prolyl‐tRNA synthetase 1 (PARS1) has attracted much interest in controlling pathologic accumulation of collagen containing high amounts of proline in fibrotic diseases. However, there are concerns about its catalytic inhibition for potential adverse effects on global protein synthesis. We developed a novel compound, DWN12088, whose safety was validated by clinical phase 1 studies, and therapeutic efficacy was shown in idiopathic pulmonary fibrosis model. Structural and kinetic analyses revealed that DWN12088 binds to catalytic site of each protomer of PARS1 dimer in an asymmetric mode with different affinity, resulting in decreased responsiveness at higher doses, thereby expanding safety window. The mutations disrupting PARS1 homodimerization restored the sensitivity to DWN12088, validating negative communication between PARS1 promoters for the DWN12088 binding. Thus, this work suggests that DWN12088, an asymmetric catalytic inhibitor of PARS1 as a novel therapeutic agent against fibrosis with enhanced safety.

Leucyl-tRNA synthetase 1 (LARS1) is a leucine sensor for mTORC1 signaling and regulates leucine utilization depending on glucose availability. Here, the author show that O-GlcNAcylation of LARS1 is crucial for its ability to regulate mTORC1 activity and leucine metabolism upon glucose starvation.

Efficient delivery of functional factors into target cells remains challenging. Although extracellular vesicles (EVs) are considered to be potential therapeutic delivery vehicles, a variety of efficient therapeutic delivery tools are still needed for cancer cells. Herein, we demonstrated a promising method to deliver EVs to refractory cancer cells via a small molecule-induced trafficking system. We generated an inducible interaction system between the FKBP12-rapamycin-binding protein (FRB) domain and FK506 binding protein (FKBP) to deliver specific cargo to EVs. CD9, an abundant protein in EVs, was fused to the FRB domain, and the specific cargo to be delivered was linked to FKBP. Rapamycin recruited validated cargo to EVs through protein-protein interactions (PPIs), such as the FKBP-FRB interaction system. The released EVs were functionally delivered to refractory cancer cells, triple negative breast cancer cells, non-small cell lung cancer cells, and pancreatic cancer cells. Therefore, the functional delivery system driven by reversible PPIs may provide new possibilities for a therapeutic cure against refractory cancers.

This work presents an illustration of Nagra’s AMAC (Advanced Methodology for Activation Characterization) approach to the South Korean pressurized water reactor Kori-1 decommissioning. The results achieved are supported by the existing experience from the detailed AMAC applications to Swiss NPPs and are used not only for a demonstration of the applicability of AMAC to South Korean NPPs, but also for a first approximation of the activated waste volumes to be expected from Kori-1. A packaging concept based on the above activation characterization is also presented, using the AMAC algorithmic optimization software ALGOPACK leading to the minimum number of waste containers needed given the selected packaging constraints. Nagra’s AMAC enables effective planning before and during NPP decommissioning, including recommendations for cutting profiles for diverse reactor components and building structures. Finally, it is expected to lead to significant cost savings by reducing the number of expensive waste containers, by optimizing a potential melting strategy for metallic waste as well as by significantly limiting the number of radiological measurements. All information about Kori-1 used for the purpose of this study was collected from publicly available sources.

Summary: Chemical agents that specifically exploit metabolic vulnerabilities of cancer cells will be beneficial but are rare. The role of oxidative phosphorylation (OXPHOS) in promoting and maintaining triple-negative breast cancer (TNBC) growth provides new treatment opportunity. In this work, we describe AuPhos-19, a small-molecule gold(III)-based agent bearing a chiral phosphine ligand that selectively disrupts mitochondrial metabolism in murine and human TNBC cells but not normal epithelial cells. AuPhos-19 induces potent cytotoxic effect with half maximal inhibitory concentration (IC50) in the nanomolar range (220–650 nM) across different TNBC cell lines. The lipophilic cationic character of AuPhos-19 facilitates interaction with mitochondrial OXPHOS. AuPhos-19 inhibits mitochondria respiration and induces significant AMPK activation. Depolarization of the mitochondria membrane, mitochondria ROS accumulation, and mitochondria DNA depletion provided further indication that AuPhos-19 perturbs mitochondria function. AuPhos-19 inhibits tumor growth in tumor-bearing mice. This study highlights the development of gold-based compounds targeting mitochondrial pathways for efficacious cancer treatment.

Abstract X-ray induced acoustic imaging (XAI) is an emerging biomedical imaging technique that can visualize X-ray absorption contrast at ultrasound resolution with less ionizing radiation exposure than conventional X-ray computed tomography. So far, medical linear accelerators or industrial portable X-ray tubes have been explored as X-ray excitation sources for XAI. Here, we demonstrate the first feasible synchrotron XAI (sXAI). The synchrotron generates X-rays, with a dominant energy of 4 to 30 keV, a pulse-width of 30 ps, a pulse-repetition period of 2 ns, and a bunch-repetition period of 940 ns. The X-ray induced acoustic (XA) signals are processed in the Fourier domain by matching the signal frequency with the bunch-repetition frequency. We successfully obtained two-dimensional XA images of various lead targets. This novel sXAI tool could complement conventional synchrotron applications.

ABSTRACTAs another wave of COVID-19 outbreak has approached in July 2020, a larger scale COVID-19 pediatric Asian cohort summarizing the clinical observations is warranted. Children confirmed with COVID-19 infection from the Republic of Korea, the Hong Kong Special Administrative Region (HKSAR) and Wuhan, China, during their first waves of local outbreaks were included. Their clinical characteristics and the temporal sequences of the first waves of local paediatric outbreaks were compared. Four hundred and twenty three children with COVID-19 were analyzed. Wuhan had the earliest peak, followed by Korea and HKSAR. Compared with Korea and Wuhan, patients in HKSAR were significantly older (mean age: 12.9 vs. 10.8 vs. 6.6 years, p

Objective To investigate functional outcomes after the application of a critical pathway for inpatient rehabilitation of total knee arthroplasty (TKA). Methods A total of 184 patients (57 males and 127 females; average age, 71.5±5.9 years) who underwent unilateral or bilateral TKA were included. The critical pathway included early, intensive individualized rehabilitation exercises. Patients completed the following performance-based physical function tests: the stair climbing test (SCT), 6-minute walk test (6MWT), and Timed Up and Go test (TUG) as well as measurement of isometric knee flexor and extensor strength of the operated knee, gait speed, and range of knee flexion and extension. Self-reported physical function and pain were measured using the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) and visual analog scale (VAS), respectively, and self-reported quality of life was measured using the EuroQoL 5 dimension (EQ-5D) questionnaire. These evaluations were performed preoperatively and at 1 month and 3 months postoperatively. Results Performance-based and self-reported physical function and quality of life measures improved nonlinearly over time. Specifically, the 6WMT, TUG, gait speed, WOMAC-pain, WOMAC-function, VAS, and EQ-5D scores showed a significant improvement at 1-month post-TKA, whereas SCT, peak torque of the knee extensors and flexors, and WOMAC-stiffness scores showed gradual, but substantial, improvements over 3 months. There were between-group differences (unilateral and bilateral TKA groups) in the time course of the SCT, 6MWT, TUG, VAS, WOAMC-stiffness, and WOMAC-function results. Conclusion Patients who underwent critical pathway rehabilitation after TKA showed significant improvements in functional measurements during the first 3 months post-surgery.

Objective To determine post-operative physical performance factors associated with gait speed in patients surgically treated for hip fracture. Methods Cross-sectional data from 59 patients (16 males and 43 females; mean age, 79.2±9.1 years) who underwent hip fracture surgery were enrolled. Patients completed a 10-meter walk test (10MWT) to assess gait speed. Additional physical performance tests included the Timed Up and Go test (TUG), the Berg Balance Scale (BBS), maximum voluntary isometric contraction (MVIC) of the knee extensors and flexors on the operated and non-operated sides as well as of the hip abductors (all tested using air-resistance weight machines), and analysis of spatio-temporal gait parameters at about 6 weeks after hip surgery. Results Bivariate analyses revealed a significant positive correlation between the post-operative 10MWT and the post-operative TUG, age, swing phase duration, and gait cycle duration along with a significant negative correlation between post-operative BBS score, MVIC of the knee extensors and flexors on the operated and non-operated sides, MVIC of the hip abductors, and cadence and stance phase duration. Linear regression analyses revealed that the post-operative TUG (β=0.85, p

The control of exosome release is associated with numerous physiological and pathological activities, and that release is often indicative of health, disease, and environmental nutrient stress. Tuberous sclerosis complex (TSC) regulates the cell viability via the negative regulation of the mammalian target of rapamycin complex (mTORC1) during glucose deprivation. However, the mechanism by which viability of TSC-null cells is regulated by mTORC1 inhibition under glucose deprivation remains unclear. Here, we demonstrated that exosome release regulates cell death induced by glucose deprivation in TSC-null cells. The mTORC1 inhibition by rapamycin significantly increased the exosome biogenesis, exosome secretion, and cell viability in TSC-null cells. In addition, the increase in cell viability by mTORC1 inhibition was attenuated by two different types of inhibitors of exosome release under glucose deprivation. Taken together, we suggest that exosome release inhibition might be a novel way for regression of cell growth in TSC-null cells showing lack of cell death by mTORC1 inhibition.

Photonic fibers are important raw materials for structurally colored fabrics. In particular, the mechanochromic fibers potentially provide color‐tunable clothes, like chameleon skins. Herein, microfluidic jetting to continuously produce mechanochromic fibers in a controlled manner is used. The jet is produced by flow‐focusing the photocurable dispersions in a surfactant‐laden carrier fluid using microfluidic devices. The dispersions contain monodispersed silica particles in an elastomer‐forming resin. As the silica particles have repulsive interparticle potential in the resin, they spontaneously organize into a nonclose‐packed regular array, developing structural colors. The jet of the dispersions is photocured in situ by irradiation of ultraviolet at the exit of the microfluidic channel, continuously producing the photonic fibers. As the interparticle separation among silica particles is shortened along the radial direction by stretching the elastic fibers, the structural colors are dynamically blue shifted. Also, the original colors are reversibly recovered by relaxing the fibers as the deformation is fully elastic. The nonclose‐packed array of inelastic silica particles provides a wide range of color tuning and high reversibility. Moreover, microfluidic jetting enables the production of Janus fibers composed of two distinct color domains, which enriches the available structural colors through color mixing.

Abstract The reaction of gold reagents [HAuCl4•3H2O], [AuCl(tht)], or cyclometalated gold(III) precursor, [C^NAuCl2] with chiral ((R,R)-(-)-2,3-bis(t-butylmethylphosphino) quinoxaline) and non-chiral phosphine (1,2-Bis(diphenylphosphino)ethane, dppe) ligands lead to distorted Au(I), (1, 2, 4, 5) and novel cyclometalated Au(III) complexes (3, 6). These gold compounds were characterized by multinuclear NMR, microanalysis, mass spectrometry, and X-ray crystallography. The inherent electrochemical properties of the gold complexes were also studied by cyclic voltammetry and theoretical insight of the complexes was gained by density functional theory and TD-DFT calculations. The complexes effectively kill cancer cells with IC50 in the range of ~0.10–2.53 μΜ across K562, H460, and OVCAR8 cell lines. In addition, the retinal pigment epithelial cell line, RPE-Neo was used as a healthy cell line for comparison. Differential cellular uptake in cancer cells was observed for the compounds by measuring the intracellular accumulation of gold using ICP-OES. Furthermore, the compounds trigger early – late stage apoptosis through potential disruption of redox homeostasis. Complexes 1 and 3 induce predominant G1 cell cycle arrest. Results presented in this report suggest that stable gold-phosphine complexes with variable oxidation states hold promise in anticancer drug discovery and need further development.

Abstract Objective Myelinated Schwann cells (SCs) in adult peripheral nerves dedifferentiate into immature cells in demyelinating neuropathies and Wallerian degeneration. This plastic SC change is actively involved in the myelin destruction and clearance as demyelinating SCs (DSCs). In inherited demyelinating neuropathy, pathologically differentiated and dysmyelinated SCs constitute the main nerve pathology. Methods We investigated whether this SC plastic status in human neuropathic nerves could be determined by patient sera to develop disease‐relevant serum biomarkers. Based on proteomics analysis of the secreted exosomes from immature SCs, we traced p75 neurotrophin receptor (p75) and neural cell adhesion molecule 1 (NCAM) in the sera of patients with peripheral neuropathy. Results Enzyme‐linked immunosorbent assay (ELISA) revealed that p75 and NCAM were subtype‐specifically expressed in the sera of patients with peripheral neuropathy. In conjunction with these ELISA data, pathological analyses of animal models and human specimens suggested that the presence of DSCs in inflammatory neuropathy and of supernumerary nonmyelinating or dysmyelinating SCs in inherited neuropathy could potentially be distinguished by comparing the expression profiles of p75 and NCAM. Interpretation This study indicates that the identification of disease‐specific pathological SC stages might be a valuable tool for differential diagnosis of peripheral neuropathies.

The initiation of translation is a highly regulated process that contributes to specific gene expression programs. Here the authors find that, in vertebrate, threonyl-tRNA synthetase (TRS) can act as a scaffold for the initiation machinery to stimulate the translation of a specific set of mRNAs.

Open-wedge high tibial osteotomy (OW-HTO) is an effective surgical intervention for medial-compartment knee osteoarthritis. However, the osteotomized gap might be a disadvantage in OW-HTO because it can cause problems such as delayed bone union or loss of correction. These issues can be minimized by using autologous bone graft in the osteotomized gap, which is known to be the fastest and most clinically satisfactory gap filler. The primary mechanical stability of the osteotomy site in OW-HTO is essential for early weight bearing after surgery. Therefore, we introduce the combination of a cylindrical autologous bone grafting technique and a metallic block insertion for faster bone union and better primary stability of the site in OW-HTO. We expect that the described procedure will enable early postoperative weight bearing and, thereby, allow an early return to normal function.

Objective: To identify preoperative physical performance factors that predict stair-climbing ability at one month after total knee arthroplasty. Design: Prospective cohort study. Setting: University-based rehabilitation centre. Subjects: Eighty-four patients who underwent a primary unilateral total knee arthroplasty. Methods: Before and one month post-operation, the patients completed physical performance tests, including a stair-climbing test, a 6-minute walk test, a Timed Up-and-Go test, tests of the isometric flexor and extensor strength of the operated and non-operated knees, and instrumental gait analysis. Disease-specific physical function was measured by the Western Ontario McMaster Universities Osteoarthritis Index. Results: Correlation analysis showed that postoperative stair-climbing test scores were significantly correlated with preoperative physical performance and function. Linear regression analysis showed that postoperative stair-ascent scores were correlated with preoperative Timed Up-and-Go test scores and peak torque of the extensor of the operated knee. Postoperative stair-descent scores were positively correlated with preoperative stair-descent scores and age. Conclusion: The results show that preoperative balance ability and quadriceps strength in the operated knee could influence postoperative stair-climbing ability at one month after total knee arthroplasty. These findings will be useful for developing pre- and post-operative rehabilitation strategies for improving stair-climbing ability in the early stages after total knee arthroplasty.

Contractors responsible for the whole execution of engineering, procurement, and construction (EPC) projects are exposed to multiple risks due to various unbalanced contracting methods such as lump-sum turn-key and low-bid selection. Although systematic risk management approaches are required to prevent unexpected damage to the EPC contractors in practice, there were no comprehensive digital toolboxes for identifying and managing risk provisions for ITB and contract documents. This study describes two core modules, Critical Risk Check (CRC) and Term Frequency Analysis (TFA), developed as a digital EPC contract risk analysis tool for contractors, using artificial intelligence and text-mining techniques. The CRC module automatically extracts risk-involved clauses in the EPC ITB and contracts by the phrase-matcher technique. A machine learning model was built in the TFA module for contractual risk extraction by using the named-entity recognition (NER) method. The risk-involved clauses collected for model development were converted into a database in JavaScript Object Notation (JSON) format, and the final results were saved in pickle format through the digital modules. In addition, optimization and reliability validation of these modules were performed through Proof of Concept (PoC) as a case study, and the modules were further developed to a cloud-service platform for application. The pilot test results showed that risk clause extraction accuracy rates with the CRC module and the TFA module were about 92% and 88%, respectively, whereas the risk clause extraction accuracy rates manually by the engineers were about 70% and 86%, respectively. The time required for ITB analysis was significantly shorter with the digital modules than by the engineers.

Leucyl-tRNA synthetase (LRS) is a leucine sensor of the mTORC1 pathway. Here, the authors identify inhibitors of the GTPase activating function of LRS, not affecting its catalytic activity, and demonstrate that the leucine sensor function of LRS can be a new target for mTORC1 inhibition.

A new radiation scale is proposed. With empathy toward the vast majority of people who are not well versed in radiation and related matters, and thus suffering from misunderstanding that breeds unnecessary fear of radiation, the aim of proposing a new radiation scale, radiation index (RAIN), is to put the general public at ease with the concept of radiation. RAIN is defined in dimensionless numbers that relate any specific radiation dose to a properly defined reference level. As RAIN is expressed in plain numbers without an attached scientific unit, the public will feel comfortable with its friendly look, which in turn should help them understand radiation dose levels easily and allay their anxieties about radiation. The expanded awareness and proper understanding of radiation will empower the public to feel that they are not hopeless victims of radiation. The correspondence between RAIN and the specific accumulated dose is established. The equivalence will allow RAIN to serve as a common language of communication for the general public with which they can converse with radiation experts to discuss matters related to radiation safety, radiation diagnosis and therapy, nuclear accidents, and other related matters. Such fruitful dialogues will ultimately enhance public acceptance of radiation and associated technologies.

PurposeTo examine the correlation of depression with Internet use and body image perception, and to analyze the risk factors of depression in a total of 920 students in Seoul, Korea.MethodsStudents were recruited by contacting school principals and teachers and were encouraged to fill out a self-report questionnaire designed specifically for this study in July of 2008.ResultsFemale participants had an increased risk for depression than did male participants (adjusted odds ratio [aOR], 1.790; 95% confidence interval [CI], 1.330–2.410, P

Idiopathic pulmonary fibrosis (IPF), a chronic disease of unknown cause, is characterized by abnormal accumulation of extracellular matrix (ECM) in fibrotic foci in the lung. Previous studies have shown that the transforming growth factor β1 (TGFβ1) and signal transducers and activators of transcription (STAT) pathways play roles in IPF pathogenesis. Glutamyl-prolyl-tRNA-synthetase (EPRS) has been identified as a target for anti-fibrosis therapy, but the link between EPRS and TGFβ1-mediated IPF pathogenesis remains unknown. Here, we studied the role of EPRS in the development of fibrotic phenotypes in A549 alveolar epithelial cells and bleomycin-treated animal models. We found that EPRS knockdown inhibited the TGFβ1-mediated upregulation of fibronectin and collagen I and the mesenchymal proteins α-smooth muscle actin (α-SMA) and snail 1. TGFβ1-mediated transcription of collagen I-α1 and laminin γ2 in A549 cells was also down-regulated by EPRS suppression, indicating that EPRS is required for ECM protein transcriptions. Activation of STAT signaling in TGFβ1-induced ECM expression was dependent on EPRS. TGFβ1 treatment resulted in EPRS-dependent in vitro formation of a multi-protein complex consisting of the TGFβ1 receptor, EPRS, Janus tyrosine kinases (JAKs), and STATs. In vivo lung tissue from bleomycin-treated mice showed EPRS-dependent STAT6 phosphorylation and ECM production. Our results suggest that epithelial EPRS regulates the expression of mesenchymal markers and ECM proteins via the TGFβ1/STAT signaling pathway. Therefore, epithelial EPRS can be used as a potential target to develop anti-IPF treatments.

Oblique submicron-scale structures are used in various aspects of research, such as the directional characteristics of dry adhesives and wettability. Although deposition, etching, and lithography techniques are applied to fabricate oblique submicron-scale structures, these approaches have the problem of the controllability or throughput of the structures. Here, we propose a simple X-ray-lithography method, which can control the oblique angle of submicron-scale structures with areas on the centimeter scale. An X-ray mask was fabricated by gold film deposition on slanted structures. Using this mask, oblique ZEP520A photoresist structures with slopes of 20° and 10° and widths of 510 nm and 345 nm were fabricated by oblique X-ray exposure, and the possibility of polydimethylsiloxane (PDMS) molding was also confirmed. In addition, through double exposure with submicron- and micron-scale X-ray masks, dotted-line patterns were produced as an example of multiscale patterning.

We examine whether analysts’ cash flow forecasts improve firm value. First, we analyze whether the joint issuance of financial analysts’ earnings and cash flow forecasts improve firm value. Second, we analyze whether the quality of analysts’ cash flow forecasts improve firm value. The empirical results of our study are as follows. First, the joint issuance of analysts’ earnings and cash flow forecasts has a significantly positive effect on firm value; providing cash flow forecasts reduces information asymmetry and increases earnings quality, thereby increasing corporate value. Second, the quality of analysts’ cash flow forecasts has a significantly positive effect on firm value; the more accurate cash flow forecasts are, the higher firm value is. Our study provides empirical evidence for that the conclusion that cash flow forecasting information produced by financial analysts provides useful information for capital market participants in economic decision making.

In this research, a Ni-Fe mold insert for the efficient replication of high aspect-ratio microstructure arrays was fabricated via hard X-ray lithography and an electroforming process. For the X-ray exposure on a photoresist, a gold-based X-ray mask was prepared with conventional UV photolithography. The gold thickness was designed to be over 15 μm to prevent development underneath the absorber and to enhance the adhesion strength between the photoresist and substrate. By using the X-ray mask, a positive-type photoresist was selectively exposed to X-ray under an exposure energy of 4 kJ/cm3. Thereafter, the exposed region was developed in a downward direction to effectively remove the residual photoresist from the substrate. During the evaporation process, deionized water mixed with a surface additive prevented the bending and clustering of the photoresist microstructure arrays by lowering the capillary force, resulting in a defect-free mother structure for electroforming. Lastly, the mother structure was uniformly Ni-Fe electroformed on a conductive substrate without the formation of any pores or detachment from the substrate. Based on the proposed microfabrication process, a Ni-Fe mold insert with a 183 μm pattern size, 68 μm gap size, 550 μm height, 2116 microcavities and a hardness of 585 Hv was precisely manufactured. It can be utilized for the mass production of high aspect ratio metal and ceramic microstructure arrays in micro molding technologies.

Human infections with Campylobacter are primarily associated with the consumption of contaminated poultry meat. In this study, we isolated Campylobacter jejuni from retail raw chicken and duck meat in Korea and compared their aerotolerance, antibiotic resistance, and virulence gene prevalence. Whereas C. jejuni isolates from chicken dominantly belonged to multilocus sequence typing (MLST) clonal complex (CC)-21, CC-45 is the common MLST sequence type in duck meat isolates. C. jejuni strains from both chicken and duck meat were highly tolerant to aerobic stress. The prevalence of virulence genes was higher in C. jejuni strains from chicken than those from duck meat. However, antibiotic resistance was higher in duck meat isolates than chicken isolates. Based on the prevalence of virulence genes and antibiotic resistance, fluoroquinolone-resistant C. jejuni strains harboring all tested virulence genes except virB11 were predominant on retail poultry. Fluoroquinolone-resistant C. jejuni strains carrying most virulence genes were more frequently isolated in summer than in winter. The comparative profiling analysis in this study successfully demonstrated that antibiotic-resistant and pathogenic strains of C. jejuni are highly prevalent on retail poultry and that retail duck meat is an important vehicle potentially transmitting C. jejuni to humans in Korea.

Phasianus colchicus is not only a beautiful bird but also a great value in science and under the threat of endanger. Hence, the aim of this study was to isolate the pheasant male germ cells (mGCs) and then induce them into elongated sperm-like cells in vitro. The mGCs were purified and enriched by a two-step plating method based on the different adherence velocities of mGCs and somatic cells. The percentage of the c-kit positive cells and c-kit negative cells examined by flow cytometry analysis (FCA) was 92.87% and 2.57%, respectively. Subsequently, the mGCs were induced for 48h in DMEM/F12 medium supplemented factors such as retinol acid, testosterone and bovine FSH, followed by 5 weeks in culture. We found that some elongated sperm-like cells appeared initially in vitro under inducement of stimulated factors. The elongated sperm-like cells showed in the expression of changed morphology and post-transcriptional marker such as spermatid associated (SPERT), spermatid perinuclear RNA binding protein (STRBP), round spermatid basic protein 1 (RSBN1) and SPER1L. Moreover, in DNA content identified assay, induced cells showed that the 1C DNA population markedly increased in differentiated group but it was not change in undifferentiated group. Successful in vitro differentiation of pheasant testicular germline cells into spermatids appears to offer extremely attractive potential for the conservation of endangered birds and treatment of male infertility.

Familial Mediterranean fever (FMF) is the most common Mendelian autoinflammatory disease, characterized by uncontrolled activation of the innate immune system that manifests as recurrent brief fever and polyserositis (e.g., peritonitis, pleuritic, and arthritis). FMF is caused by autosomal recessive mutations of the Mediterranean fever gene, MEFV which encodes the pyrin protein. Although FMF predominantly affects people from Mediterranean and Middle Eastern ethnic origins, 3 cases of FMF have been reported in Korea since 2012. We report another case of FMF in Korea in which the patient presented with a month-long fever without serositis. After treatment with colchicine was initiated, the patient’s symptoms quickly subsided. The response to colchicine was helpful for diagnosis. We compare the FMF genotypes in Korea with in other countries. Studying FMF cases in Korea will help establish the best MEFV exons to use for screening and diagnosis of Korean FMF.

In this study, a fabrication method of tapered microstructures with high aspect ratio was proposed by deep X-ray lithography. Tapered microstructures with several hundred micrometers and high aspect ratio are demanded owing to the high applicability in the fields of various microelectromechanical systems (MEMS) such as optical components and microfluidic channels. However, as the pattern and gap size were downsized to smaller micro-scale with higher aspect ratio over 5, microstructures were easily deformed or clustered together due to capillary force during the drying process. Here, we describe a novel manufacturing process of tapered microstructures with high aspect ratio. To selectively block the deep X-ray irradiation, an X-ray mask was prepared via conventional ultraviolet (UV) lithography. A double X-ray exposure process with and without X-ray mask was applied to impose a two-step dose distribution on a photoresist. For the clear removal of the exposed region, the product was developed in the downward direction, which encourages a gravity-induced pulling force as well as a convective transport of the developer. After a drying process with the surface additive, tapered microstructures were successfully fabricated with a pattern size of 130 μm, gap size of 40 μm, and aspect ratio over 7.

This paper aims to give an overview of the methods to inherently prevent human errors and to effectively mitigate the consequences of such errors by securing defense-in-depth during plant management through the advanced man-machine interface system (MMIS). It is needless to stress the significance of human error reduction during an accident in nuclear power plants (NPPs). Unexpected shutdowns caused by human errors not only threaten nuclear safety but also make public acceptance of nuclear power extremely lower. We have to recognize there must be the possibility of human errors occurring since humans are not essentially perfect particularly under stressful conditions. However, we have the opportunity to improve such a situation through advanced information and communication technologies on the basis of lessons learned from our experiences. As important lessons, authors explained key issues associated with automation, man-machine interface, operator support systems, and procedures. Upon this investigation, we outlined the concept and technical factors to develop advanced automation, operation and maintenance support systems, and computer-based procedures using wired/wireless technology. It should be noted that the ultimate responsibility of nuclear safety obviously belongs to humans not to machines. Therefore, safety culture including education and training, which is a kind of organizational factor, should be emphasized as well. In regard to safety culture for human error reduction, several issues that we are facing these days were described. We expect the ideas of the advanced MMIS proposed in this paper to lead in the future direction of related researches and finally supplement the safety of NPPs.

Many recent studies have focused on traceback schemes with the aim of finding the source of spoofed malicious packets and tracing the path of denial-of-service attacks. Although such schemes are academically well known, most exhibit some critical points in wireless sensor networks, which could become a significant issue as they are increasingly used for IP networks. This paper suggests an advanced traceback scheme based on existing Bloom filter methods. The proposed traceback scheme extends the basic Bloom filter design, enabling it to identify which entity added a given element, albeit with the incursion of false positives. However, our scheme allows only specific tracebacks, which can reduce the false positive rate of a node near a sink. Performance results show that the scheme can perform efficient tracebacks with very few false positives.

Wireless machine-to-machine sensor networks with multiple radio interfaces are expected to have several advantages, including high spatial scalability, low event detection latency, and low energy consumption. Here, we propose a network model design method involving network approximation and an optimized multi-tiered clustering algorithm that maximizes node lifespan by minimizing energy consumption in a non-uniformly distributed network. Simulation results show that the cluster scales and network parameters determined with the proposed method facilitate a more efficient performance compared to existing methods.

This paper presents look-ahead energy management system for a grid-connected residential photovoltaic (PV) system with battery under critical peak pricing for electricity, enabling effective and proactive participation of consumers in the Smart Grid’s demand response. In the proposed system, the PV is the primary energy source with the battery for storing (or retrieving) excessive (or stored) energy to pursue the lowest possible electricity bill but it is grid-tied to secure electric power delivery. Premise energy management scheme with an accurate yet practical load forecasting capability based on a Kalman filter is designed to increase the predictability in controlling the power flows among these power system components and the controllable electric appliances in the premise. The case studies with various operating scenarios demonstrate the validity of the proposed system and significant cost savings through operating the energy management scheme.

Streptococcus pneumoniae remains a leading cause of invasive infections including bacteremia and meningitis, as well as mucosal infections such as otitis media and pneumonia among children and adults. The 7-valent pneumococcal conjugate vaccine (PCV7) was licensed for use among infants and young children in many countries including Korea. The routine use of PCV7 has resulted in a decreased incidence of invasive pneumococcal disease (IPD) by the vaccine serotypes among the vaccinees and substantial declines in IPD among unvaccinated populations such as older children and adults as well. In addition, there are increasing evidences to suggest that routine immunization with PCV7 is changing the epidemiology of pneumococcal diseases such as serotype distribution of IPD, nasopharyngeal colonization, and antibiotic resistance patterns. In contrast, there is an increase in the number of IPDs caused by nonvaccine serotypes, though it is much smaller than overall declines of vaccine serotype diseases. Several vaccines containing additional serotypes have been developed and tested clinically in order to expand the range of serotypes of Streptococcus pneumoniae. Recently two new pneumococcal protein conjugate vaccines, 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13), have been approved for use in several countries including Korea. This report summarizes the recommendations approved by the Committee on Infectious Diseases, the Korean Pediatric Society.

PurposeEnterovirus 71, one of the enteroviruses that are responsible for both hand-foot-and-mouth disease and herpangina, can cause neural injury. During periods of endemic spread of hand-foot-andmouth disease caused by enterovirus 71, CNS infections are also frequently diagnosed and may lead to increased complications from neural injury, as well as death. We present the results of our epidemiologic research on the clinical manifestations of children with CNS infections caused by enterovirus 71.MethodsThe study group consisted of 42 patients admitted for CNS infection by enterovirus 71 between April 2009 and October 2009 at the Department of Pediatrics of 5 major hospitals affiliated with the Catholic University of Korea. We retrospectively reviewed initial symptoms and laboratory findings on admission, the specimen from which enterovirus 71 was isolated, fever duration, admission period, treatment and progress, and complications. We compared aseptic meningitis patients with encephalitis patients.ResultsOf the 42 patients (23 men, 19 women), hand-foot-and-mouth disease was most prevalent (n=39), followed by herpangina (n=3), upon initial clinical diagnosis. Among the 42 patients, 15 (35.7%) were classified as severe, while 27 (64.3%) were classified as mild. Factors such as age, fever duration, presence of seizure, and use of intravenous immunoglobulin (IVIG) were statistically different between the 2 groups.ConclusionOur results indicate that patients with severe infection caused by enterovirus 71 tended to be less than 3 years old, presented with at least 3 days of fever as well as seizure activity, and received IVIG treatment.

This research suggests a Denial of Service (DoS) detection method based on the collection of interdependent behavior data in a sensor network environment. In order to collect the interdependent behavior data, we use a base station to analyze traffic and behaviors among nodes and introduce methods of detecting changes in the environment with precursor symptoms. The study presents a DoS Detection System based on Global Interdependent Behaviors and shows the result of detecting a sensor carrying out DoS attacks through the test-bed.

Conventional nighttime face detection studies mostly use near-infrared (NIR) light cameras or thermal cameras, which are robust to environmental illumination variation and low illumination. However, for the NIR camera, it is difficult to adjust the intensity and angle of the additional NIR illuminator according to its distance from an object. As for the thermal camera, it is expensive to use as a surveillance camera. For these reasons, we propose a nighttime face detection method based on deep learning using a single visible-light camera. In a long-distance night image, it is difficult to detect faces directly from the entire image due to noise and image blur. Therefore, we propose Two-Step Faster region-based convolutional neural network (R-CNN) based on the image preprocessed by histogram equalization (HE). As a two-step scheme, our method sequentially performs the detectors of body and face areas, and locates the face inside a limited body area. By using our two-step method, the processing time by Faster R-CNN can be reduced while maintaining the accuracy of face detection by Faster R-CNN. Using a self-constructed database called Dongguk Nighttime Face Detection database (DNFD-DB1) and an open database of Fudan University, we proved that the proposed method performs better compared to other existing face detectors. In addition, the proposed Two-Step Faster R-CNN outperformed single Faster R-CNN and our method with HE showed higher accuracies than those without our preprocessing in nighttime face detection.

In this paper, we developed a method of fabricating polymer microstructures at various angles on a single substrate via synchrotron X-ray lithography coupled with simple dimensional transformations. Earlier efforts to create various three-dimensional (3D) features on flat substrates focused on the exposure technology, material properties, and light sources. A few research groups have sought to create microstructures on curved substrates. We created tilted microstructures of various angles by simply deforming the substrate from 3D to two-dimensional (2D). The microstructural inclination angles changed depending on the angles of the support at particular positions. We used convex, concave, and S-shaped supports to fabricate microstructures with high aspect ratios (1:11) and high inclination angles (to 79°). The method is simple and can be extended to various 3D microstructural applications; for example, the fabrication of microarrays for optical components, and tilted micro/nanochannels for biological applications.

In this information age, different kinds of photosensitive materials have been used in the manufacture of information storage devices. But these photosensitive materials have the bane of low diffraction efficiency. In order to solve this problem, we have synthesized a novel photosensitive polymer from epoxy-based azopolymers (with three types of azochromophores). Furthermore, we have studied the interaction between this newly synthesized azopolymer and ionic liquids (ILs). For this purpose, we have used the ammonium and imidazolium families of ILs, such as diethylammonium dihydrogen phosphate (DEAP), tributylammonium methyl sulfate (TBMS), triethylammonium 4-aminotoluene-3-sulfonic acid (TASA), and 1-methylimidazolium chloride ([Mim]Cl). To investigate the molecular interaction between azopolymer and ILs, we have used the following spectroscopic methods of analysis: UV-visible spectroscopy, photoluminescence (PL) spectroscopy, Fourier transformed infrared spectroscopy (FT-IR), and confocal Raman spectroscopy. In this study, we have developed new photosensitive materials by combining polymer with ILs.